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《对外经贸实务》期刊几个核心评价指标评析作者：康存辉周莉来源：《对外经贸实务》2012年第03期《对外经贸实务》杂志自1983年创刊以来，先后被北京大学图书馆评为1992、1996、2000、2008版全国中文类、贸易经济类核心期刊；2011年开始，北图改为三年评审，该刊又继续被评为2011年版的全国中文类、贸易经济类核心期刊（第六版），得到国内外广大读者的充分肯定和广泛赞誉，成为业界颇具影响的品牌杂志。
目前，该刊由武汉纺织大学和中国国际贸易学会联合主办，对外经济贸易大学中国WTO研究院协办，并成立了以商务部、联合国贸发会议、中国国际贸易学会等社会知名专家、学者组成的顾问团，被中国期刊网、万方数据、维普资讯网、博看网、思博网、龙源期刊网等数据库全文收录。
在办刊过程中，该刊突出理论与实务相结合，常年开设名家专稿、大趋势、环球经营人物、国际观察、国际商务论坛、WTO实务、国际规则与标准化、国内外市场、外贸业务探讨、服务贸易、跨国投资、案例分析、中外物流业、热点问题、经贸资讯、特稿推荐等特色栏目，贴近企业、贴近外经贸经营管理活动，力求服务实践，创新理论，成为外经贸仁人志士学术交流的大舞台。
基于该刊近年来的办刊质量和水平都取得了较大的进步，本文将对该刊在2009-2011年三年中几个核心评价指标进行评析，以期为进一步提高该刊的学术影响力作一个参照。
一、载文量与基金论文比载文量是所有评价指标的基数，而基金论文数特别国家级基金论文数是衡量期刊论文学术质量的重要指标，其基金论文比越高，表明该期刊的影响力越大。
从表1我们可以清楚的看到，《对外经贸实务》的基金论文比呈现出一个良好的发展态势，特别是国家级的基金数量逐年递增幅度很大，表明该刊的影响力和感召力显著增强。
与此同时，本刊还吸收了大量的政府职能部门的专稿、特稿，为提升本刊的政策性、引导性提供了很好的支撑，正如联合国贸发会议秘书长素帕猜所说，《对外经贸实务》是一份很重要的杂志，为中国的对外经贸做出了很大贡献。
ORIGINAL PAPERHuman breath analysis:methods for sample collection and reduction of localized background effectsAudrey N.Martin &George R.Farquar &A.Daniel Jones &Matthias FrankReceived:13August 2009/Revised:30September 2009/Accepted:5October 2009/Published online:22October 2009#Springer-Verlag 2009Abstract Solid-phase microextraction (SPME)was ap-plied,in conjunction with gas chromatography –mass spectrometry,to the analysis of volatile organic compounds (VOCs)in human breath samples without requiring exhaled breath condensate collection.A new procedure,exhaled breath vapor (EBV)collection,involving the active sampling and preconcentration of a breath sample with a SPME fiber fitted inside a modified commercial breath-collection device,the RTube ™,is described.Immediately after sample collection,compounds are desorbed from the SPME fiber at 250°C in the GC-MS injector.Experiments were performed using EBV collected at −80°C and at room temperature,and the results compared to the traditional method of collecting exhaled breath condensate at −80°C followed by passive SPME sampling of the collected condensate.Methods are compared in terms of portability,ease-of-use,speed of analysis,and detection limits.The need for a clean air supply for the study subjects is demonstrated using several localized sources of VOC contaminants including nail polish,lemonade,and gasoline.Various simple methods to supply clean inhaled air to a subject are presented.Chemical exposures are used to demonstrate the importance of providing cleaned air (organic vapor respirator)or an external air source (tubing stretched to a separate room).These techniques allow for facile data interpretation by minimizing background con-taminants.It is demonstrated herein that this active SPME breath-sampling device provides advantages in the forms of faster sample collection and data analysis,apparatus portability and avoidance of power or cooling requirements,and performance for sample collection in a contaminated environment.Keywords Bioanalytical methods .Breath analysis .GC-MS .VOC .Breath condensateIntroductionThe desire for non-invasive medical diagnostics and the measurement of occupational and incidental chemical exposure has placed growing emphasis on the development of robust techniques for collection and analysis of con-stituents in exhaled human breath.Human breath can be collected and analyzed as exhaled breath condensate (EBC)or exhaled breath vapor (EBV).EBC [1]and EBV are easily collected,even by the subject in the home.Analyses of EBC have focused on inorganic compounds such as NO,and volatile organic compounds (VOCs);over 3,000VOCs were detected in human breath in a single study [2].Compounds observed in human breath have two sources:compounds that are present in the ambient air and are inhaled and subsequently exhaled into the breath sample (exogenous compounds),or compounds that are endemic to the subject,formed in vivo and passed into the exhaled breath via diffusion from the blood into the alveoli of the lungs (endogenous compounds)[2,3].Since the develop-ment of VOC analysis in breath several decades ago [4],research has focused on the study of endogenous com-pounds;changes which may be indicative of many medical conditions including asthma [5–9],chronic obstructiveA.N.Martin :G.R.Farquar (*):M.Frank Lawrence Livermore National Laboratory,Livermore,CA 94550,USA e-mail:gfarquar@ A.N.Martin :A.D.Jones Michigan State University,East Lansing,MI 48824,USAAnal Bioanal Chem (2010)396:739–750DOI 10.1007/s00216-009-3217-7pulmonary disease[10,11],diabetes[12,13],breast cancer [14–16],lung cancer[17–23],lung infection[9,24,25], and transplant rejection[26–28].Breath analyses targeted at identifying exposure to occupational or incidental chem-icals(exogenous compounds)have also been presented [29–36].Studies by the U.S.Environmental Protection Agency(EPA)have measured constituents in breath of human subjects throughout the United States,documenting exposures to chemicals such as automotive exhaust and cigarette smoke[32,35–38].Many techniques have been pursued for analysis of exhaled breath including enzyme-linked immunosorbent assay(ELISA)[39,40],colorimetric tests[41,42],optical spectroscopy[42,43],high-performance liquid chromatog-raphy[8,42],ion mobility spectrometry[25],liquid chromatography–mass spectrometry(LC-MS)[8,10,11], GC with flame ionization detection(GC-FID)[44–47],and GC-MS[16,17,22,34,48–50].Ekips Technologies (Norman,OK)has developed a system called the Breath-meter[6],approved by the FDA for research studies.The Breathmeter uses tunable diode laser spectroscopy to detect both organic and inorganic components in breath.The mid-IR absorptions of many compounds allows for internal calibration and wide-range detection with laser tuning.In separate developments,Aerocrine Inc.(Solna,Sweden)has marketed the first FDA-approved system called NIOX Flex which uses chemiluminescence to monitor NO in exhaled breath with a detection limit of2ppb[51].Toda et al. developed a breath isoprene detection system based on its chemiluminescence after reaction with ozone with a limit of detection of0.6ppbv[52].Achieving low detection limits can present challenges owing to low analyte concentrations and the complexity of breath.To avoid concentration of constituents needed to achieve low detection limits,Plodinec and Wang developed cavity ring-down spectroscopy for the detection of breath acetone in a single breath[53].Amirav et al.demonstrated the use of gas chromatography–electro-lyzer-fed FID(GC-EFID)for breath detection of ethanol, isoprene,pentane,and acetone[54].This system generated its own combustion gases from water and thus was gas cylinder-free making it more field-portable[54].Sacks et ed GC-GC for breath detection,achieving limits of detection in the parts per trillion range[55].The analytical challenges that confront breath analysis arise from typical and low VOC concentrations(parts per billion by volume and below)in breath.This difficulty is compounded by dilution of VOCs by extraneous air during sampling as well as incomplete trapping of VOCs during condensation when EBC is collected.To circumvent this, several techniques have been developed to preconcentrate breath-sample constituents before analysis.Gordin and Amirav developed the‘Snifprobe’as a novel preconcentra-tion method[56].The Snifprobe consists of a small length of capillary or porous-layer open tubular(PLOT)column that preconcentrates sample constituents.Breath was drawn through the Snifprobe for5s,after which the entire column segment was placed inside a direct/dirty sample introduc-tion device(DSI)that was then inserted into the GC injector for thermal desorption[56].A limit of detection for ethanol was reported in the low ppb(v/v)region[56]. Several researchers have also used a sorbent material to sample from a bag or chamber containing a breath sample [19,21,35,44,45,50,52].In this manner,preconcentra-tion takes place after breath collection,which increases the time of sample collection and analysis.Other groups have created in-line preconcentration methods[35,57–61].For example,Phillips et al.at Menssana Research,Inc.(New-ark,NJ)have developed a breath-collection apparatus (BCA)which incorporates a sorbent trap in-line with the breath flow so that VOCs are preconcentrated as the breath sample is collected,speeding up the analysis process[2,12, 14,17,18,20,24,27,57,62,63].Several generations of this instrument have been developed,the latest being the BCA 6.0(Menssana Research,Inc.,Newark,NJ) [64].One of the more promising tools for breath VOC preconcentration is solid-phase microextraction(SPME) which was described in more detail in a recent review [29].SPME sampling can be performed passively,where a breath sample is obtained and a SPME fiber exposed to it at a later time,or actively,where a SPME fiber is exposed to breath as it is exhaled[3].Wang et ed passive sampling to preconcentrate breath samples obtained in Tedlar®sampling bags,obtaining sub nanogram per milliliter detection limits for many VOCs[46].Mutti et ed a similar technique,collecting breath samples into Teflon bulbs into which a SPME fiber was inserted for preconcentration,achieving limits of detection on the order of10−12M[22].Grote and Pawliszyn have used SPME for active breath sampling[65].The SPME fiber was inserted into an inert tube serving as a mouthpiece, and acetone,isoprene,and ethanol were analyzed using GC-MS[65].Because of the influence of exogenous VOCs on the air exhaled by a subject,some emphasis has been placed on ensuring the inhaled air supply of a subject is clean.One solution is to provide a closed source of air for the subject [19,21,31,50,66,67].Although effective,this method is reagent-consuming and compromises the portability of the testing apparatus.In other studies,subjects have been required to remain in the sampling environment for a set period of time to allow equilibration with the ambient air [12,46,63].Such procedures make the process more time-consuming for subjects and require a single sampling location for optimal comparisons of multiple subjects. Other reports have attempted to remove contaminants from the ambient air using charcoal filters[67,68].Many studies740 A.N.Martin et al.have not cleansed the inhaled air supply[8,11,23,25,39, 42,44–47,52,59,69–72].A common technique is to collect a background sample of the ambient air at the same time as the subject who has reached equilibrium with the room air donates a breath sample.The alveolar gradient is then calculated[63,73](concentration in the breath−concentration in the ambient air)and is thought to eliminate any effects of contaminated inhaled air[2,12,14,17,18, 20,24,27,57,61,62].A positive alveolar gradient suggests that VOC was produced in vivo while a negative alveolar gradient indicates the source of the VOC is external to the body[74].While this technique has advantages in the determination of VOC kinetics and for metabolite profiling,data interpretation is based on the assumption that equilibrium exists for all VOCs between the body and the ambient air.In the current study,a side-by-side comparison of three different breath-collection methods is performed using a standard EBC collection device,the RTube™(Respiratory Research,Inc.,Charlottesville,V A),and modifications of this device.These modifications reduce the time of analysis from sampling to results by approximately30%to27min (compared to using the standard device and method),as well as eliminate the need for a freezer or liquid nitrogen, making the sampling device more field-friendly,and improve analyte limits of detection.Also in the current study,additional RTube™modifications and methods of providing clean inhaled air are described.The results demonstrate the need for such purification of inhaled air in some cases, e.g.,for situations where sources of background or contamination are localized on or near the subject donating breath.ExperimentalMaterialsFrozen lemonade concentrate(Safeway/V ons Lemonade, Safeway,Inc.,Pleasanton,CA)was purchased from a local supermarket and reconstituted according to the manufac-turer’s instructions.Samples were used the day of recon-stitution after reaching room temperature(24°C).Nail Polish(ORLY Nail Color,Orly International,Inc.,Los Angeles,CA)was obtained from commercial sources and used as is.Gasoline(89-octane automotive grade)was obtained from a local gas station.D-Camphor was obtained from J.T.Baker,Inc.(Phillipsburg,NJ).A65.3-mM solution was made in a1:4solution of H2O:methanol and stored in a glass vial.(1S)-(−)-β-pinene(99%)was obtained from Alfa Aesar(Ward Hill,MA)and+/−α-limonene(95%)was obtained from TCI America,Inc. (Portland,OR).SamplingFour healthy,nonsmoking adults were recruited as subjects for this study.All subjects had no known respiratory ailments and did not report any routine chemical exposure on a questionnaire.The Institutional Review Board(IRB)at Lawrence Livermore National Laboratory(LLNL,Liver-more,CA)as well as the IRB at Michigan State University (East Lansing,MI)approved the study and formal written informed consent was obtained from each subject prior to participation.Methods of breath-sample collectionSeveral methods were explored for the collection of breath samples.Collection of EBC and exhaled breath vapor at−80°C (EBV−80°C)The RTube™(Fig.1a)is a commercially available,FDA-approved,disposable EBC collection sys-tem.The subject inhales through the mouthpiece via a one-way valve(valve A)fitted with a saliva trap to prevent sample contamination.The subject then exhales through the mouthpiece into a polypropylene collection tube via ac.)a.)b.)Valve AValve BSPMEFiberHousing2ndValve BFig.1EBC and EBV collection devices.a The commercially available RTube™;b The RTube™was modified for EBV collection by the addition of a plastic fitting to hold a SPME fiber for active sampling;c The additional modification of the RTube™to provide an enclosed environment for SPME sampling as well as the addition of a respirator to purify inhaled airHuman breath analysis741second one-way valve (valve B).The polypropylene collection tube is placed inside an aluminum sleeve (not shown)cooled in a −80°C freezer prior to collection.In this configuration,water vapor and VOCs in exhaled breath passing through the collection tube condense and collect at the base of polypropylene tube.The RTube ™was slightly modified to allow for simultaneous vapor collection onto a SPME fiber above the EBC.A plastic fitting was constructed from a second RTube ™(Fig.1b )which attached directly to the top of the RTube ™and served as a mount for a SPME sampler.A SPME fiber (65µm PDMS/DVB Stableflex fiber,Sigma-Aldrich,St.Louis,MO),previously thermally conditioned in the GC injection port per manufacturer ’s instructions,was fitted into this mount and extended into the polypro-pylene tube with the end of the fiber extending approxi-mately 3.7cm into the tube.The subjects breathed at normal frequency and tidal volume through the mouthpiece for 10min,typically yielding 0.7–2.5mL of EBC.Immediately after collection,the analytes collected on the SPME fiber from EBV −80°C were analyzed by GC-MS,as described in more detail below.At the same time,a standard volume,0.5mL,of EBC was aliquoted into a disposable polypropylene microcentrifuge tube (Fisher Scientific,Pittsburgh,PA).After analysis of the EBV −80°C was complete,the same SPME fiber (thermally cleaned and conditioned during the EBV −80°C analysis in the GC-MS)was directly immersed in the aliquot of EBC for 10min (direct exposure).After this exposure,the analytes collected on the SPME fiber from EBC were analyzed by GC-MS.Three replicate samples were collected from each of three subjects over several days to validate this collection procedure.Collection of EBV-RT Exhaled breath vapor at room temperature (EBV-RT)was collected using the modified RTube ™(Fig.1b )at room temperature,without using the aluminum condenser.The subject breathed at a normal frequency and tidal volume through the mouthpiece of the RTube ™for 10min while the SPME fiber was exposed toexhaled breath inside the polypropylene tube.After collection,the sample was immediately analyzed by GC-MS.To reduce confounding effects such as diet,ambient intake air,and activity,the EBC and EBV −80°C samples were obtained simultaneously and the EBV-RT sample was subsequently obtained within 1h or less.All EBV −80°C and EBV-RT samples were analyzed immediately after collection;all EBC samples were sampled using SPME shortly after collection and then immediately injected.Noticeable warming of the aluminum condenser occurred during sampling,as has been previously documented [40].A typical EBC collection yielded 0.7–2.5mL EBC during the 10-min collection time.EBV-RT collection typically yielded <200µL condensate which was discarded.Three replicate samples were collected from each of 3subjects over several days to validate this collection procedure.Methods of sample collection in the presence of localized contaminantsSeveral procedures were used to modify the source of a subject ’s inhaled air in order to reduce the influence of localized contaminants on breath samples.RTube ™modification with PVC tubing A 12-foot long segment of FDA-approved clear PVC tubing (0.5in.I.D.,0.75in.O.D.,VWR,Inc.,West Chester,PA)was fitted to the base of valve A on the modified RTube ™(Fig.1b )using a plastic fitting.Tubing was stretched into a different room (air space)than that in which breath samples were collected.Human subjects breathed at normal fre-quency and tidal volume through the mouthpiece while blocking nasal inhalation for 10min.After collection,the EBV-RT collected on the SPME fiber was analyzed immediately.Three samples were collected from each of two subjects over several days to validate this collection procedure.2.003.004.005.006.007.008.009.0010.00Retention Time (min)A b u n d a n c e (a .u .)Fig.2GC/MS total ionchromatograms of breath samples from a single human subject.Samples were obtained using sev-eral collection methods:EBC with a −80°C condenser (black trace ,bottom ),EBV −80°C (green trace ,middle ),and EBV-RT (red trace ,top ).Arrows indicate several peaks with increased signal in the EBV samples compared to the EBC sample.Chromatograms are offset for clarity742 A.N.Martin et al.RTube ™modification with respirator A commercial or-ganic vapor respirator cartridge with a P100particulate filter (99.97%minimum filter efficiency,Lab Safety Supply Inc.,Janesville,WI)was fitted to the plastic fitting holding valve A via a Viton®o-ring (approximately 2.5cm diameter)and a machined brass fitting.Plastic caps,the polypropylene tube,and valve B from a second RTube ™were used to isolate the SPME fiber from the outside air as shown in Fig.1c .The subject held the RTube ™with the air inlet of the attached respirator cartridge positioned over approximately 125mL of lemonade,allowing the head-space of the lemonade to be inhaled through the cartridge.The subject then repeated the experiment without the respirator cartridge,holding the RTube ™air inlet in the headspace of the lemonade.This experiment was also repeated as the subject painted a standardized square with nail polish,with the inhaled air containing the headspace of the polish.Again,this experiment was repeated without the respirator cartridge,with the RTube ™air inlet directly drawing from the nail polish headspace.After collection of each sample,the EBV-RT collected on the SPME fiber wasTable 1Breath VOCs and corresponding GC retention times tentatively identified in GC/MS analysis of a typical EBV-RT sample from human breath (no known exposure)Peak CompoundRT 1Carbon dioxide 1.32Acetone 1.543Acetic acid1.854Allyl methyl sulfide2.55Unidentified compound2.636(Z )-1-(Methylthio)-1-propene 2.827Methyl isobutyl ketone 2.868Formic acid 39Toluene3.13104,4-Dimethyl-2-pentene 3.411Butyl ester acetic acid 3.55123-Furaldehyde3.77134-Hydroxy-4-methyl-2-pentanone 3.86142-Furanmethanol 3.9715o -Xylene4.0816p -Xylene4.1817Methoxy-phenyl-oxime 4.3118Styrene4.419Ethylene glycol monoisobutyl ether 4.49202-Methyl-bicyclo[3.1.0]hex-2-ene4.75216,6-Dimethyl-2-methylenebicyclo[3.1.1]heptane 4.8422Benzaldehyde5.1323Phenol5.19246-Methyl-5-hepten-2-one 5.2925Cyclofenchene 5.3026Beta-pinene 5.3427Isopentyl ether 5.4628Alpha-terpinene 5.66292-Ethyl-1-hexanol 5.730o -Cymene5.7331D -Limonene5.7832Eucalyptol5.83332-Methyl tridecane 5.96344,6-Dimethyl undecane6.0135Gamma-terpinene 6.0436Isooctylvinyl ether 6.16372,5-Furandicarboxaldehyde 6.1938Alpha-terpinene6.339Alpha-p -dimethylstyrene 6.3440Nonanal6.4341D -Fenchyl alcohol 6.6442Plinol A 6.7643L -isopulegol 6.8944Camphor 6.9245Menthone 6.9646Isopregol747Ethyl benzoate7.05Table 1(continued)Peak CompoundRT 484-Isopropyl-1-methylcyclohexanol 7.13494-Terpineol 7.1850Alpha-terpineol 7.29514-Ethyl octane7.35525-Hydroxymethylfurfural 7.4353Undecane7.58543-Methyl dodecane 7.6755Tridecane7.75562,6,10-Trimethyl dodecane 7.8257Unidentified alkane 7.8558Isomenthol acetate 8.0259Unidentified alkane 8.5460Unidentified alkane 8.661Unidentified alkane 8.6362Unidentified alkane 8.8163Unidentified alkane 8.964Dihydropseudoionone 9.18652,6-Dimethyl heptadecane 9.25661-Dodecanol9.3567Unidentified compound 9.4868Hexyloctylether9.5369Butylated hydroxytoluene 9.6270Diethyl phthalate 10.1871Heptadecane10.24722,2-Dimethyl-3-octanone 10.88732,2-Dimethyl-4-octen-3-ol11.16Human breath analysis743analyzed immediately by GC-MS.Samples were collected from three subjects over several days to validate this collection procedure.The efficacy of the respirator for cleansing the inhaled air was also tested using commercial gasoline.To prevent unnecessary exposure to harmful chemicals a human subject was not used to collect these data;a polyethylene synthetic lung substitute was developed to simulate human respiration.The synthetic lung substitute was fabricated to approximate adult tidal volume (500mL)[75]and allowed air to be pulled into the ‘lung ’and expelled from the lung in a piston fashion.The ‘lung ’was pumped to simulate the inhalation and exhalation of a normal adult respiratory pattern with a ‘breath ’being taken every 8–10s.The synthetic lung was attached to an RTube ™,simulating a subject inhaling and exhaling through the sample collection device.The headspace of a tray of gasoline (approximately 100mL)was the source of the simulated inhaled air of the lung substitute,and as the lung substitute was expanded,the headspace ‘inhaled breath ’passed through the RTube ™and into the ‘lung ’.As the lung substitute was contracted,‘breath ’was expelled from the lung,through the RTube ™and passed over the SPME fiber.This process of simulated inhalation and exhalation was repeated for 10min.Samples were collected over several days to validate this collection procedure.A second respirator was then attached in series to the first respirator and the experiment repeated,in order to study the effect of additional filtration.Sample analysis by GC-MSAn Agilent (Santa Clara,CA)6890N GC equipped with a SPME inlet sleeve and an Agilent J&W DB-5MS column(30m×0.25mm×0.25µm,equivalent to 5%phenyl,95%methylpolysiloxane)was used for the separation of all compounds.Helium (99.999%,Praxair,Inc.,Danbury,CT)was used as a carrier gas and the GC was operated in constant pressure mode (10psi).The injector temperature was held at 250°C,and the oven temperature was held at 40°C for 1min,then ramped at 20°C/min to 300°C,then held for 3min.Detection was carried out with an Agilent 5973MS detector (Santa Clara,CA),using 70eV electron ionization and operated in scan mode (m /z 40–450)at 3.54scans/s,with the source held at 230°C and the mass analyzer (quadrupole)held at 150°C.The detector was autotuned using ChemStation software (Agilent,Santa Clara,CA),and the tune confirmed before each set of experiments.A blank SPME fiber (unexposed)was analyzed at the beginning of each day to ensure system calibration and fiber cleanliness.Chem-Station software was used for data collection and analysis.Compounds were identified based on comparison of their mass spectra with those in the NIST Mass Spectral Library (RMatch >700,NIST MS Search 2.0,NIST,Gaithersburg,MD)as well as mass spectra published in the literature,and comparison of retention time with pure chemicals (camphor,acetone,toluene,β-pinene,limonene)when available.Peak areas were calculated using the RTE integrator contained in the ChemStation software.Table 2GC/MS total ion chromatogram peak areas of several compounds tentatively identified in total ion current chromatograms of human breath samples collected as EBV −80C or EBV-RT compared to corresponding peak area of EBC total ion current chromatograms CompoundRT (min)Factor increase in measuredpeak area vs.EBC-80CEBV −80CEBV-RTAllyl methyl sulfide2.50 5.0 2.1(Z )-1-(methylthio)-1-propene 2.829.93.7D -Limonene 5.78 6.810.2Ethyl benzoate 7.05 1.64.6Tridecane7.75 2.08.4Unidentified alkane7.85 2.19.0Butylated hydroxytoluene9.624.98.4These chromatographic peaks are indicated by the arrows in Fig.201M 2M 3M 4M 5M 6M1.501.582K4K 6K 8K 10K 3.82 3.860.4K0.8K 1.2K 1.6K 2K 6.90 6.92c.)a.)b.)Retention Time (min)A b u n d a n c e(a .u .)Fig.3Extracted ion chromatograms (XIC)of breath samples from a single subject (EBC).One sample was collected 215min after the subject received a manicure with an RTube ™modified with PVC tubing which provided inhaled air from a separate room (black trace ,bottom ).Another sample was obtained 317min after receiving the manicure,and was obtained with the standard unmodified RTube ™(red trace ,top ).a The XIC of m /z 45,identified as a major fragment ion from isopropyl alcohol,b the XIC of m /z 43,corresponding to a major fragment ion from diacetone alcohol,and c the XIC of m /z 152corresponding to the molecular ion of camphor744A.N.Martin et al.Results and discussionMethods of breath-sample collectionFigure 2shows example total ion chromatograms (TIC)from a single human subject using each collection method.The EBV-RT samples yielded an average of 23%more peaks in the chromatograms than the EBC samples from the same subject using the same integration parameters (n =4).Table 1shows a list of observed compounds and their retention times tentatively identified in EBV-RT breath samples.The vapor samples also provided increased peak areas for many peaks.For example,D -limonene showed a tenfold increase in peak area when a vapor phase sample was collected and analyzed relative to an EBC sample.The area increase of several such peaks is shown in Table 2.Thus,for many compounds,vapor phase collection of exhaled breath provides increased signal and increased information.Methods of sample collection in the presence of localized contaminantsSeveral methods were tested herein to determine if the source of a subject ’s inhaled air could be modified to reduce the influence of a subject ’s surroundings on the subject ’s breath samples.Breath samples (EBC)from a single subject with a fresh manicure were obtained at regular intervals over the course of a single day (7h)using the RTube ™modified with PVC tubing.The PVC tubing was extended out of the sampling room in order to provide a ‘clean ’air source.Immediately after the manicure,the concentration of several VOCs in breath,tentatively identified as isopropyl alcohol,camphor,and diacetone alcohol,increased and then exponentially decayed with time (data not shown).Isopropyl alcohol and camphor were listed as ingredients on the nail polish used;diacetone alcohol was not a listed ingredient,but is commonly formedvia an aldol condensation of acetone [76],which was a listed ingredient.The breath sample obtained 215min after the manicure showed minimal detectable signal from these compounds.An additional sample was then taken 317min post-manicure using an unmodified RTube ™(no tubing).This chromatogram showed higher concentrations of isopropyl alcohol,camphor,and diacetone alcohol than found with the RTube ™modified with PVC tubing.Extracted ion chromatograms for each of these peaks are shown in Fig.3.By holding the RTube ™to obtain the breath sample,the subject ’s hands (i.e.,painted fingernails)were in close proximity to the mouth and nose,inadvertently causing the subject to inhale a higher concentration of compounds directly from the nail polish.The use of the PVC tubing to provide an air source removed from the subject ’s personRetention Time (min)A b u n d a n c e (a .u .)Fig.4Total ion current chromatograms of breath samples from a single subject (EBV-RT)collected using a variety of inhaled air sources:ambient air (red trace ,top ),ambient air through a respirator (blue trace ,middle ),and ambient air from a separate room than sampling (green trace,bottom).The subject painted a simulated fingernail with commercial nail polish during pounds labeled are listed ingredients of the nail polish or byproducts of ingredients.Chromatograms are offset for clarityTable 3Reduction in extracted ion chromatogram peak area for several ingredients of nail polish detected in human breath obtained with a respirator or PVC tubing CompoundPeak area reduction (%)With respiratorWith tubingIsopropyl alcohol 9096Ethyl acetate9294Diisopropoxy methane 8996Toluene9498Mesityl oxide 9499Butyl acetate 9298Diacetone alcohol 9694Camphor (1)95100Camphor (2)9799Peak areas were calculated by integration of a specific extracted ion chromatograms (XIC)for each compound,and are displayed relative to the peak area value obtained without modifying the inhaled air sourceHuman breath analysis745。
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Accepted by ASME J. of Biomechanical Engineering on 03/10/2006One-Dimensional Models of the Human Biliary SystemW.G. Li a , X.Y. Luo b, A.G. Johnson c, N.A.Hill b, N. Bird c, & S.B. Chin aa Department of Mechanical Engineering, University of Sheffield, Sheffield, S1 3JD, UKb Department of Mathematics, University of Glasgow, Glasgow, G12 8QW, UKc Academic Surgical Unit, Royal Hallamshire Hospital, Sheffield, S10 2JF, UKCorresponding Author:Dr. X.Y. LuoDepartment of Mathematics,University of Glasgow,Glasgow, G12 8QW, UKFax: 0044-141-330 4111E-mail: X.Y.Luo@AbstractThis paper studies two one-dimensional models to estimate the pressure drop in the normal human biliary system for Reynolds number up to 20. Excessive pressure drop during bile emptying and refilling may result in incomplete bile emptying, leading to stasis and subsequent formation of gallbladder stones. The models were developed following the group’s previous work on the cystic duct using numerical simulations. Using these models, the effects of the biliary system geometry, elastic property of the cystic duct, and bile viscosity on the pressure drop can be studied more efficiently than with full numerical approaches. It was found that the maximum pressure drop occurs during bile emptying immediately after a meal, and is greatly influenced by the viscosity of the bile and the geometric configuration of the cystic duct, i.e. patients with more viscous bile or with a cystic duct containing more baffles or a longer length, have the greatest pressure drop. It is found that the most significant parameter is the diameter of the cystic duct; a 1% decrease in the diameter increases the pressure drop by up to 4.3%. The effects of the baffle height ratio and number of baffles on the pressure drop are reflected in the fact that these effectively change the equivalent diameter and length of the cystic duct. The effect of the Young’s modulus on the pressure drop is important only if it is lower than 400Pa; above this value, a rigid-walled model gives a good estimate of the pressure drop in the system for the parameters studied.Keywords: bile flow, cystic duct, gallstone, pressure dropNomenclatureACross-sectional area of collapsed ductm 2 0A Cross-sectional area of duct at zero transmural pressure m 2 1ACross-sectional area of flow at point 1 in Fig. 4 m 2 2A Cross-sectional area of the flow at point 2 in Fig. 4 m 2 1c Sudden contraction head-loss coefficient 2cSudden expansion head-loss coefficient 3c Head loss coefficient in a bend 4cHead loss coefficient in a 90o benddInner diameter of duct mm EYoung’s modulus of materials Pa fDarcy friction factor hThickness of wall or baffle mm HBaffle heightmm j Number of nodeJMaximum number of element p KStiffness of wall Pa LLength of ductm m L Equivalent length due to minor pressure loss m n Number of bafflesc nMaximum number of baffles p Internal duct pressure Pa e p External duct pressure Pa QBile flow rateml/min ReReynolds number, Re ud ν= r Inner radius of duct, πA r =mtTime min uBile velocity in cystic duct, A Q u = m/s V Bile volume in gallbladder ml x Duct centre-line coordinate m α Area ratio, 0A A =αμBile dynamic viscositymPa.s νBile kinematic viscosity, νμρ= mm 2/s θ The half of central angle of baffle cut rad ρDensity of bilekg/m 3 σPoisson’s ratioξBaffle height ratio, CD H d ξ=L Δ Distance between two successive baffles in cystic duct m p ΔPressure dropPa m p Δ Minor pressure drop in cystic ductPa te p Δ Minor pressure drop in T-junction during emptying Pa th p ΔMinor pressure drop in T-junction during refill Pa x ΔInterval of elementm Subscriptsb Baffle CBD Common bile ductCD Cystic duct CHDCommon hepatic ductEM Emptyingeq Equivalent id Ideal, straight and circular pipe inInlet of ductmax Maximum value min Minimum value outOutlet of ductRF Refilling1 IntroductionBiliary diseases such as cholelithiasis and cholecystitis necessitate surgical removal of the gallbladder (GB), which is the most commonly performed abdominal operation in the West. Some 60,000 operations for gallbladder disease are performed in the UK each year [1] at a cost to the National Health Service (NHS) of approximately £60 million per annum [2]. In order to understand the causes of these diseases, it is important to understand the physiological and mechanical functions of the human biliary system. The human biliary system consists of the gallbladder, cystic duct, common hepatic duct and common bile duct (Fig. 1). The human gallbladder is a thin-walled, pear-shaped sac which measures approximately 7-10cm in length and ~3cm in width. Its average storage capacity is 20-30ml. The human cystic duct is approximately 3.5cm long and 3mm wide and merges with the common bile duct. The mucosa of the proximal cystic duct is arranged into 3-7 crescentic folds or valves known as the spiral valves of Heister. The human common duct is normally about 10-15cm long and 5mm wide, in which the hepatic common duct is ~4cm long. The common bile duct merges with the pancreatic duct before entering the duodenum at the ampulla [4].Whilst the anatomical and physiological aspects of the human biliary system have been studied extensively, a little is known about flow mechanics in the system. Torsoli and Ramorino [5] measured pressures in the biliary tree and found them to vary from 0-14cm H2O (1cm H2O=100Pa) in the resting gallbladder to approximately 12-20cm H2O in the common bile duct. Earlier experimental work by Rodkiewcz and Otto [6] showed that bile behaves like a Newtonian fluid, although this has been challenged recently [7, 8, 9]. Kimura [10] found that the relative viscosity of bile is between 1.8-8.0, while Joel [11] found it is between 1.77-2.59. The relative viscosity is defined as the dynamic viscosity of the investigated fluid compared with that of distilled water, both at the same temperature. Tera [12] measured the dynamic viscosity of gallbladder bile by using eight 8cm-long capillary tubes with a diameter of 0.2mm. It was found that the normal gallbladder bile was layered and the relative viscosity of the top, thinnest layer was 2.1 and the bottom thickest layer was 5.1. Bouchier et al [13] also reported that relative viscosity, determined by a capillary flow viscometer, was greater in pathological gallbladder bile than normal gallbladder bile and both were more viscous than hepatic duct bile. Although the concentration of normal gallbladder bile affected the bileviscosity, in pathological and hepatic bile, the content of mucous was the major factor determining viscosity. Cowie et al [14] showed that the mean viscosity of bile from gallbladders containing stones was greater than that from healthy ones. The presence of mucous in gallbladders with stones was likely to account for the differences in viscosity based on the viscosity results using a Cannon-Fiske capillary viscometer at room temperature.The complicated geometry of the biliary tree makes it difficult to estimate the pressure drop during bile emptying using the Poiseuille formula. Rodkiewiz et al [15] found that flow of bile in the extrahepatic biliary tree of dog was related to the associated pressure drop by a power law and differed from that for laminar flow in a rigid tube. Dodds et al [16] calculated the volume variations of the gallbladder during emptying using the ellipsoid and sum-of-cylinders methods from the gallbladder images. Jazrawi et al [17] performed simultaneous scintigraphy and ultrasonography for 14 patients with gallstones and 11 healthy controls and studied the postprandial refilling, turnover of bile, and turnover index. They found that in postprandial healthy controls, the gallbladder handles up to six times its basal volume within 90min, but this turnover of bile is markedly reduced in cholelithiasis causing a reduced washout effect of the gallbladder contents, including cholesterol crystals (They didn’t actually measure the cholesterol crystals). Deenitchin [18] investigated the relationships between a complex cystic duct and cholelithiasis in 250 patients with cholelithiasis and 250 healthy controls. It was found that the patients with gallstones had significantly longer and narrower cystic ducts than those without stones. The results suggested that complex geometry of the cystic ducts may play an important role in cholelithiasis. An increase in the cystic duct resistance has been shown to result in sludge formation and eventually stones in the gallbladder [19, 20, 21, 22, 23]. Recently, Bird et al [24] have investigated the effects of different geometries and their anatomical functions of the cystic ducts.It is now generally accepted that prolonged stasis of bile in the gallbladder is a significant contributing factor to gallstone formation, suggesting that fluid mechanics, in particular, the pressure drop which is required to overcome the resistance of bile flow during emptying, may play an important role in gallstone formation. Unusually high gallbladder pressures could be a cause of acute pain observed in vivo, and also indicate that the gallbladder could not empty satisfactorily, increasing the likelihood of forming cholesterol crystals.Ooi et al [25] performed a detailed numerical study on flow in two- and three-dimensional cystic duct models. The cystic duct models were generated from patients’ operative cholangiograms and acrylic casts. The pressure drops in these models were compared with that of an idealised straight duct with regular baffles or spiral structures. The influences of different baffle heights, numbers, and Reynolds numbers on the pressure drop were investigated. They found that an idealised duct model, such as a straight duct with baffles, gives qualitative measurements that agree with the realistic cast models from two different patients. Experimental work has also been carried out to validate the CFD predictions in the simplified ducts [26]. Thus the simplified models can be used to provide some physical insights into the general influence of cystic duct geometry on the pressure drop [25]. However, their CFD modelling was limited to rigid cystic duct models only, an extending it to compliant model will be very much time consuming.In this paper, in order to obtain a global view of the total pressure drop in the whole biliary system and to consider the importance of the effects of fluid-structure interaction in the human cystic duct, we propose two one-dimensional models of the human biliary system, one with a rigid wall and one with an elastic wall. These models are based on the three-dimensional straight duct with regular baffles used by Ooi et al [25]. The rigid model is validated against the three-dimensional simulations, and the differences between the elastic and rigid models are discussed. Using these models, the effects of physical parameters such as the cystic duct length, diameter, baffle height ratio, number of baffles, the Young’s modulus, and the bile viscosity, on the pressure drop are studied in detail. Both refilling and emptying processes are modelled, and the bile flow in the hepatic and common bile ducts is also taken into consideration. It is hoped that these models can be further developed to provide some fast, qualitative estimates of pressure drop based on real time in vivo data of patients’ biliary systems and therefore be used to aid clinical diagnosis in the longer term.The remainder of the paper is organized as follows. The characteristics of geometry and flow are described in Section 2, and the one-dimensional models are introduced in Section 3. The results and discussion are given in Section 4, followed by the conclusions.2 Characteristics of Geometry and FlowAnatomical descriptions of the biliary system date back to the 18th century when Heister [4] reported spiralling features in the lumen of the cystic duct and called them “valves”. Although later researchers doubted the valvular function, the term “valves of Heister” is still in use. The gross anatomy of the biliary system shown in Fig.1 begins from the gallbladder neck which funnels into a cystic duct. Spiralling mucous membranes are generally prominent in the proximal part of the cystic duct (pars spiralis or pars convoluta ) which then smoothes out to form a circular lumen at the distal end (pars glabra ). Although the actual geometry of the cystic, common hepatic and bile ducts is very complicated and subject dependent, and the ducts are all curved, to obtain a system view we can schematically represent the human biliary system as in Fig. 2.The flow directions of the bile during gallbladder emptying immediately after meal, and during refilling are also shown in Fig. 2. Usually, it takes about half an hour for emptying and several hours (until the next meal) for refilling. The gallbladder volume variation with time in both emptying and refilling is shown in Fig. 3 [4]. From this figure, we can derive the corresponding flow rate (or volume flux) Q (=dV dt ). For a healthy person, the average bile density ρ is about 1000kg/m 3, the same as water, and the range of diameter of the cystic duct is about CD d =1-4mm [24]. The temporal acceleration of bile (u t ρ∂) is approximately 10-3 m/s 2 in the emptying phase and 10-5 m/s 2 in the refilling, and can therefore be ignored in our model. In addition, the maximum Reynolds number (Re =4CD Q d πν) estimated for a cystic duct with diameter of 1mm and bile kinematical viscosity ν=1.275 mm 2/s is about 20 duringnormal emptying, and even smaller during refilling. Hence the flow is laminar. Finally, for a healthy person without gallstones, the bile can be reasonably considered as a Newtonian fluid [27].3 The One-Dimensional ModelsThe pressure drop during emptying is believed to have a link with the stone formation in gallbladder [18]. Our primary aim, therefore, is to predict this pressure drop in a mathematical model of the human biliary system. It is noted that the key structure contributing to the pressure drop is the cystic duct, while the hepatic and common bile ducts offer little resistance or geometric changes during emptying and refilling. Therefore to simplify the pressure dropprediction, the modelling focuses on the non-linear flow features in the cystic duct, while Poiseuille flow is assumed in the other two biliary ducts. In the following, the effects of the baffles in the cystic duct are considered in order to determine the equivalent diameter and length. The effects of the elastic wall are then considered on a straight model of the cystic duct using the concept of equivalent diameter and length.3.1 The Rigid Wall ModelFor a given flow rate, the flow resistance is defined as the pressure drop required to drive the flow along the duct. This pressure drop generally includes viscous losses and any local flow separation or vortex loss.3.1.1 Equivalent diameter and lengthIt is assumed that the common bile duct and the common hepatic duct are straight tubes and join at a T-junction (Fig. 2). To model the effects of the cystic duct baffles on the flow, following Ooi et al [25], the baffles are arranged in the simplified manner, shown in Fig. 4. Unlike in the straight tube, the flow in the cystic duct needs to negotiate its way around the baffles and the worst scenario is shown by the arrow in Fig. 4. Thus the key problem is to estimate the equivalent length L eq , and the equivalent diameter, d eq , treating the cystic duct as an “equivalent straight pipe”. Once this is done, it is straightforward to calculate the pressure drop in the cystic duct assuming Poiseuille flow.The equivalent diameter for the cystic duct, CD d , is dependent on the number of baffles, as well as the baffle height. From Fig. 4 we can see that the bile flow travels twice the distance from points 1 to 2 between any two baffles in the duct, and 1A and 2A are the corresponding cross-sectional areas at points 1 and 2. The sector area 1A can be easily calculated from)212CD CD A d H d θ=− , (1)where θ is half of the centre angle of the baffle cut, and is written as))))11tan 22tan CDCD H d H d θππ−−⎧−⎪⎪=⎨⎪+−⎪⎩222CD CD CD H d H d H d >=< , (2)for a given tube with fixed values of CD L and CD d , 1A depends on the baffle height H only.The maximum diameter of the flow passage is equal to the diameter of cystic duct CD d without baffles, i.e.,max eq CD d d = , (3)It is shown in the Appendix that for the range of parameters in which we are interested, 1A is always smaller than 2A. Therefore the minimum diameter of the flow passage is associated with 1A , i.e.,min eq d = , (4)We now assume that the equivalent diameter of cystic duct varies linearly with the number of baffles between min ,eq d and max ,eq d , i.e.(),min ,max ,min 1eq eq eq eq c n d d d d n ⎛⎞=+−−⎜⎟⎝⎠, (5)where n c is the maximum number of baffles considered. For the parameters we considered, n c =18 (for details, see Appendix).The equivalent length of the cystic duct is determined from the actual length of the flow passage along the duct plus an extra length due to the complicated flow pattern, i.e.()1eq CD m L H n L L =−++, (6)where m L denotes the extra length corresponding to the minor pressure drop due to local vortices from the cross-section area expansion, contraction and the flow path bending in the baffle zone. It can be estimated from [28] that4128eq mm d p L QπμΔ=, (7) where m p Δ is the local pressure drop predicted by Bober and Kenyon [29], i.e.()2212324241616(1)m eq eqQ Q p n c c c n d d ρρππΔ=++− . (8)Here the sudden contraction head-loss coefficient is 110.42(1)CD c A A =−, and the sudden expansion head-loss coefficient is ()2211CD c A A =− [28]. The coefficient 3c is the head-lossdue to the flow bending around the baffles and it is a function of the bending angle. For a 90o bend, 3c has been measured to be 0.75 [29]. In our model, the angle through which the flowbends around a baffle should largely depend on the baffle height ratio, ξ, and to a lesser extent, on the number of baffles too. For simplicity, however, we assume that the angle is a linear function of ξ: 3c k ξ=, where k is chosen to be 0.85. Thus, for ξ=0 (straight tubeflow), 3c =0, and for ξ = 0.9, where 3D simulations typically show that the flow turningthrough 90o around the baffles, 3c =0.75.3.1.2 The Emptying PhaseThe pressure drop in the cystic duct in the emptying phase for a given number of baffles can now be estimated for Poiseuille flow [28]4128CD eq eqQ p L d μπΔ= . (9) For the common bile duct, in the emptying phase, the pressure drop can be written as4128CBD CBD te CBDQ p L p d μπΔ=+Δ , (10) where te p Δ accounts for the pressure drop owing to the T-junction which consists of one 90o bend and one expansion, given224224241616te CD CDQ Q p c c d d ρρππΔ=+ , (11) The coefficients 4c =0.75 for 90o bend and 2c may be treated in the same manner as those for Eq. (8). Thus the total pressure drop in the biliary system during the emptying phase is44128128EM eq CBD te eq CBDQ Q p L L p d d μμππΔ=++Δ . (12)3.1.3 The Refilling PhaseLikewise, during refilling, the pressure drop in the common bile duct is expressed by Eq. (10), and the pressure drop in the common hepatic duct is4128CHD CHD th CHDQ p L p d μπΔ=+Δ , (13) where224124241616th CHD CHD Q Q p c c d d ρρππΔ=+ , (14) and the total pressure drop during refilling is44128128RF eq CHD th eq CHDQ Q p L L p d d μμππΔ=++Δ . (15)3.2 The Elastic Wall ModelIn order to obtain a more realistic description for the pressure drop in the human biliarysystem, an elastic wall model is now considered. In reality, the ducts are soft tissues made of non-linear material, i.e. the Young’s modulus varies with the internal pressure [30, 31]. However, in the first instance, it is assumed that the cystic duct is a linear, isotropic elastic material with a uniform wall thickness. The hepatic and common bile ducts are still assumed to be rigid for two reasons: one is that the Young’s modulus of these ducts is greater than that of the cystic duct [30]; the other is that the pressure variations in these two ducts are much smaller (less than 1 Pa) than in the cystic duct and, therefore, the deformation of the ducts is also much smaller.For simplicity, we model the elastic behavior of the cystic duct as an “equivalent pipe” with an equivalent length L=L eq , and a diameter d eq . In other words, the effects of baffles on the flow come implicitly through L eq and d eq (or area A eq , which varies with the transmuralpressure, i.e. internal minus external). We assume that the cystic duct is initially circular and the duodenal valve opens during emptying, which reduces the pressure in the common bile duct. This, together with the rise in the gallbladder pressure, will initiate the bile flow out of the gallbladder, which further decreases the pressure downstream in the cystic duct. Thus the transmural pressure in the downstream part of the cystic duct during emptying will become negative. As a result, the cystic duct becomes partially collapsed towards the downstream end. This fluid-structure behavior is modeled following well-known work on collapsible flows [32,33, 34].3.2.1 The elastic wall modelThe Emptying Phase The partially collapsed cystic duct is shown schematically in Fig. 5, where p e is the external pressure, and equals to the pressure in the chest, e p =1.5kPa [4](above atmospheric pressure ). We introduce a one-dimensional coordinate system originating from point ‘O’. As the bile flows down the cystic duct, the internal pressure decreases due to viscous losses, causing a decrease in transmural pressure, e p p −, from the inlet (in A ) to theoutlet (out A ). The governing equations for the flow in the elastic cystic duct are [32]Au Q = , (16)28du dp Q u dx dx Aπμρ=−− . (17) The pressure at the inlet is chosen as the reference pressure. For a given flow rate, the corresponding pressure in the duct is derived by integrating Eq. (17)2222011118'(')2xin in p p Q dx Q A x A A πμρ⎛⎞=−+−⎜⎟⎝⎠∫. (18) The constitutive equation for the duct with an elastic wall obeys the ‘tube law’ forhomogeneous elastic materials [33],()αF K p p p e =− , (19)where()323121p Eh K rσ=− , (20) and 0A A α=, ()αF is usually determined by experiments. For veins, the tube law can be expressed as [32, 34]()1032F ααα−=−. (21)Since there is no experimental data for the cystic duct, here we assume that it obeys Eq. (21). The fluid pressure estimated using Eq.(19) is ()3231032232121e Eh p p Aπαασ−=+−⎡⎤⎣⎦− . (22) Combining Eq.(18) and Eq.(22), we have()3321032222321111821210in e in x Eh p Q dx Q p A A A A ππμραασ−⎛⎞′⎡⎤−+−=+−⎜⎟⎣⎦−⎝⎠∫, (23) Equation (23) represents a one-dimensional boundary value problem, which is solved using a finite difference method. The duct is divided into J elements (J is chosen to be > 300); a typical element extending from node j to j+1 is illustrated in Fig. 5. At the (j+1)th node, ()1032323112222232121001111182121j j j j e j j j j A A Eh p Q Q x p A A A A A A πρπμσ−+++++⎡⎤⎛⎞⎛⎞⎛⎞⎛⎞+−−Δ=+−⎢⎥⎜⎟⎜⎟⎜⎟⎜⎟⎜⎟−⎝⎠⎢⎥⎝⎠⎝⎠⎝⎠⎣⎦, (24) where222202221212122212111118,21111,211118,2j x j in in j j jj j j j j j j p p Q dx Q A A A A A A p p Q Q x A A A πμρρπμ+++++⎛⎞=−+−⎜⎟⎜⎟⎝⎠⎛⎞⎛⎞=+⎜⎟⎜⎟⎜⎟⎝⎠⎝⎠⎛⎞⎛⎞=+−−Δ⎜⎟⎜⎟⎜⎟⎝⎠⎝⎠∫and j p is known. Expressing ()2121j A + in terms of A j and A j+1, Eq. (24) can also be written as ()10323231122222232110011111142121j j j j e j j j j j A A Eh p Q Q x p A A A A A A A πρπμσ−+++++⎡⎤⎛⎞⎛⎞⎛⎞⎛⎞+−−+Δ=+−⎢⎥⎜⎟⎜⎟⎜⎟⎜⎟⎜⎟⎜⎟−⎢⎥⎝⎠⎝⎠⎝⎠⎝⎠⎣⎦. (25) We employ the bisection method to solve Eq.(25) to find unknown 1j A + in region[]1000.1,2j A A A +∈ in an iterative manner.The boundary conditions are applied at the inlet (node 1) ()()0331032232121in in in e in in in A A Eh p p A απαασ−=⎧⎪⎨=+−⎪−⎩, (26) If in α=1, then in e p p =; else if 1in α>, then in e p p >. The maximum pressure drop in the cysticduct is thus CD in out p p p Δ=−, and the total pressure drop occurring during emptying is4128EM CD CBD te CBDQ p p L p d μπΔ=Δ++Δ . (27) The Refilling Phase Because the bile flow rate is very small during refilling and the refill time is at least 3 times longer than the emptying time, the cystic duct wall can be regarded asrigid during this phase. Equations (13)-(15) in the rigid model are applied to calculate the pressure drop.4 Results and Discussion4.1 ParametersThe parameters used in the models are listed in Table 1. Most of these are taken from the statistics of human ducts given by Deenitchin et al [18]. The range of values for ξ, n and CD d are chosen to be the same as in the 3D models by Ooi [25]. The gallbladder flow rate isderived from the volume-time curve in Fig. 3, which lies between 0.49 and 1.23 ml/min. The range of the Young’s modulus used for this model is based on the measurements of [30], where bile ducts from 16 healthy adult dogs were tested with a pressure ranging from 4.7kPa to 8kPa. In fact, the physiological internal pressure is normally around 1.5kPa in the human biliary system, which is outside the pressure range used by Jian and Wang [30]. In order to obtain meaningful results, we estimate the Young’s modulus for the pressure around 1.5kPa from the extrapolation of the best curve fitting from the data of [30]. The Young’s modulus chosen for the models is therefore in the range of 100Pa and 1000Pa, which corresponds to the internal pressure varying from 1.03kPa to 1.9kPa.4.2 One-Dimensional Model ValidationAs several assumptions are used in deriving the equivalent diameter and length of the one-dimensional (1D) model, here we compare our 1D model with the three-dimensional (3D) rigid cystic duct models solved with the numerical methods. Fig. 6 illustrates the pressure drop variations with Reynolds number using the rigid model for the cystic duct only, with and without baffles. The geometry and bile parameters are CD L =50mm, CD d =5mm, n =0, 2, 6,10and 14, b h h ==1mm, ρ=1000kg/m 3, ν=1mm 2/s, respectively. These results are comparedwith the corresponding 3D cystic duct CFD results provided by [25], which was quantitatively validated by experiments [26] for higher Reynolds numbers. It can be seen that the agreement between the rigid model and 3D CFD results is consistently good for all values of parameters. This suggests that we have captured the main features of the flow in the rigid cystic duct. Theelastic model is derived for a straight pipe with equivalent diameter and length to the duct with baffles, and is based on the experimental curve for a straight rubber tube [32]. Therefore, if the rigid model with the correct equivalent diameter and length is accepted as satisfactory, then the elastic model is likely to be satisfactory.4.3 Pressure Drop for the Reference Parameter SetThere are many parameters present in the model, and each can vary within its ownphysiological range. In order to isolate the effect of each individual parameter, we introduce a Reference Parameter Set (henceforth referred to as the Reference Set), which is based on averaged values of a normal human cystic duct. The Reference Set is: n =7, ξ=0.5, ν=1.275 mm 2/s, CD d =1 mm, CD L =40 mm, E =300 Pa, in α=1, and Q =1 ml/min. The effect of anyparticular parameter on the pressure drop is determined by varying this parameter while keeping all the other parameters fixed. For the rigid tube, all parameters are the same except that Young’s modulus does apply.The predicted pressure drops in the human biliary system for the Reference Set using the rigid and elastic models in the emptying and refill phases are shown in Fig. 7. Two cases are considered: in α =1 and 1.2. in α =1 is the case when the inlet of the cystic duct is notexpanded, while in α=1.2 indicates a duct expansion because this has been observed clinically.It can be seen that for in α=1 the elastic model predicts a greater pressure drop in the emptyingphase, due to the collapse of the cystic duct. It is also noted that the maximum value of the pressure drop agrees with the typical physiological observation of 20Pa to 100Pa [4, 35].The ratio of total pressure drop in the common bile duct or common hepatic duct to the total pressure drop in the cystic duct, can illustrate the importance of the pressure drop across the cystic duct in the human biliary system. The results demonstrate that the pressure drop in the common duct is less than 1.5%, and in the common hepatic duct less than 0.15% only, compared to that in the cystic duct. This justifies estimating the pressure drop in the human biliary system from the cystic duct model only, as was done by Ooi et al [25].。
Alterations in intestinal microbialflora and human disease Mohamed Othman a,b,Roberto Agu¨ero b and Henry C.Lin a,bIntroductionOur intestinal microbialflora includes a variety of micro-organisms,predominantly bacteria,which colonize the gut of all living organisms.Colonization of the gut begins at birth with thefirst exposure to theflora of the birth canal. Shortly after birth,hundreds of species of bacteria and archaea establish themselves in the human gastrointestinal tract[1,2].For decades the importance in human health of gut microbes,commonly referred to as commensalflora, despite advanced knowledge of the microbial world,has been underappreciated.The adult human intestine is home to more than400species of microbes,which normally remain confined to the distal gut where the concentration of organisms is approximately1011organ-isms per gram of content(colon)but surprisingly just100–2 organisms per gram of content in the proximal small intestine[3].The gut microflora is essential for the devel-opment of both the digestive tract itself as well as our immune system,required for the development of tissues such as Peyer’s patches and the production of immuno-globulin A[4].The gut microflora is physically separated from the host by a thin intestinal epithelial barrier.The ‘tight junctions’between the cells of the intestinal barrier precisely regulate the transport of molecules while prohi-biting the migration of microorganisms[5,6];however,this selective permeability can be altered directly by bacteria or indirectly via cytokines produced by the immune response of the host[6,7].One example of the effect of gut microbes on the host is small intestinal bacterial overgrowth(SIBO), described as a proliferation of the distal gut bacterial population,proximally,into the small intestine.SIBO may permit or facilitate translocation of those bacteria or bacterial components(antigen)across the intestinal barrier,with negative consequences to health.In this review,we focus on the effect of altered gut microbiota, as exemplified by SIBO,on the human host in the settings of acute pancreatitis,bacterial gastroenteritis,irritable bowel syndrome,inflammatory bowel disease,hepatic encephalopathy,fibromyalgia and burn injury. Intestinal motility and gut microflora in acute pancreatitisIntestinal motility can greatly affect the intestinal micro-flora and acute pancreatitis provides an interesting modela Gastroenterology Section,New Mexico VA Healthcare System,Albuquerque andb Department of Internal Medicine,University of New Mexico, Albuquerque,New Mexico,USACorrespondence to Henry C.Lin,MD, Gastroenterology Section(111F),New Mexico VA Healthcare System,1501San Pedro Dr SE, Albuquerque,NM87108,USATel:+15052651711ext.4511;fax:+15052565751;e-mail:helin@salud@Current Opinion in Gastroenterology2008, 24:11–16Purpose of reviewTo highlight the evidence supporting the role of altered commensal gutflora in human disease.While the contribution of the indigenous gut microbial community is widely recognized,only recently has there been evidence pointing to indigenousflora in disease.RecentfindingsThis review discusses recent evidence pointing to the role of altered commensal gut flora in such common conditions as irritable bowel syndrome and inflammatory bowel disease.Recent studies document the intricate relationship between the vast population of microbes that live in our gut and the human host.Since increased intestinal permeability and immune activation are consequences of an altered host–gut microbial relationship,what are the clinical effects of this shift in relationship?SummaryWe focus on the example of an abnormal expansion of gut microbialflora into the small bowel or small intestinal bacterial overgrowth and discuss the effects of bacterial overgrowth on the human host in acute pancreatitis,bacterial gastroenteritis,irritable bowel syndrome,inflammatory bowel disease,hepatic encephalopathy,andfibromyalgia and burn injury.The identification of the underlying role of altered commensal gut microbiota in these and other human diseases could lead to novel diagnostic and therapeutic strategies that would improve clinical outcome.Keywordscommensal gut bacteria,gut ecology,immunity,intestinal permeability,small intestinal bacterial overgrowthCurr Opin Gastroenterol24:11–16ß2008Wolters Kluwer Health|Lippincott Williams&Wilkins0267-13790267-1379ß2008Wolters Kluwer Health|Lippincott Williams&Wilkinsto understand the role of an altered gut microbiota on clinical disease.Acute pancreatitis can be induced in animals through bile duct ligation,resulting in impaired intestinal motility.The intestinal migrating myoelectric complexes that characterize interdigestive motility become inhibited[8].Without these lumen-obliterating, sweeping contractions that propagate from the stomach or duodenum to the terminal ileum,gut microflora is no longer contained in the distal gut,resulting in SIBO [9,10].In this example,bacterial translocation becomesa consequence of impaired intestinal motility and SIBO[11].Thesefindings have been substantiated in sub-sequent acute pancreatitis animal models not requiring bile duct ligation[12].In fact,the occurrence of SIBO was positively correlated with the severity of the pancreatitis [12].Other studies of acute pancreatitis suggest that transloca-tion of commensal gut bacteria in SIBO may be responsible for the complication of pancreatic abscess[13].The route of bacterial translocation to the pancreas,however,remains in debate[14].In one study,a peritoneal mode of transport was eliminated as the route to infection[15].Other studies find an increase in intestinal permeability occurs in patients with acute pancreatitis,suggesting bacterial trans-location across the intestinal barrier[16,17].A PCR-based analysis of serum taken from acute pancreatitis patients identified DNA from Gram-negative organisms in six of 31patients,indicating that bacterial translocation may occur in around20%of patients with this condition[18]. The evidence to support the use of prophylactic antibiotics in the setting of acute pancreatitis is conflicting.Whereas a Cochrane meta-analysis offive randomized control trials (RCTs)found a lower mortality rate associated with the use of prophylactic antibiotics[19],a more recent meta-analysis of six other RCTs indicated that prophylactic antibiotics did not significantly reduce the rates of mortality,infected necrosis,or reduce the duration of hospital stay[20].Further studies are needed to test the hypotheses that earlier antibiotic therapy targeting SIBO may be more effective in reducing complications of acute pancreatitis.Acute bacterial gastroenteritis and microflora in irritable bowel syndromeThere are numerous pathogenic organisms responsible for acute bacterial gastroenteritis.These microbes not only activate the immune response of the host but also alter the composition of the gut microflora[21 ].A complication of acute gastrointestinal infection is the subsequent development of irritable bowel syndrome(IBS).About a quarter of IBS patients recall an episode of acute gastro-enteritis prior to the onset of their IBS.Furthermore,the incidence of IBS is higher among patients who experi-enced an episode of acute bacterial gastroenteritis relative to those who have not[22].In a large prospectively con-ducted cohort study,the relative risk for developing IBS following bacterial gastroenteritis was11-fold greater than that of the control population[23].The relationship between acute gastroenteritis and IBS may be due to either altered gut microbiota,bacterial overgrowth(SIBO), or a change in the part of the host as a consequence of an acute episode of gastrointestinal infection.Three months following recovery from an acute gastroenteritis caused by Campylobacter jejuni,27%of rats had SIBO as confirmed by quantitative PCR targeting microbial DNA[24].This finding in animals recovering from acute bacterial gastro-enteritis is consistent with a growing body of evidence pointing to SIBO as the underlying cause of IBS[10]. There is also evidence of abnormal microbial fermentation in IBS patients as shown by increased excretion of micro-bially produced gases(hydrogen or methane)on the exhaled breath of IBS patients,compared with controls, after ingestion of lactulose,a nondigestible substrate during a lactulose breath test(LBT)[9,25,26].Although prevalence of an abnormal lactulose breath test in IBS patients varies,in a randomized,placebo-controlled study of patients meeting Rome I criteria for IBS,the prevalence of an abnormal LBT was84%[27].Different breath test methods and instrumentation place the prevalence of an abnormal breath test in IBS patients in the range of 30–78%[28,29].Treating IBS patients with nonabsorb-able antibiotics resulted in complete resolution of IBS symptoms in those patients who achieved a normalized breath test[28].Similarly,in the RCT,patients reported 75%global improvement in their symptoms if they were randomized to the antibiotic group and their post-treatment breath test was found to be normal[27].In con-trast,patients who were treated but failed to achieve a normalized breath test still reported a32%global improve-ment,which was significantly higher than the10% improvement reported by patients randomized to placebo. The contribution of gut microbes to symptoms of IBS is further supported by the role of microbial gases in altered bowel patterns.In the RCT[27],thefinding of breath excretion of methane alone was associated exclusively with constipation;and this observation was confirmed in a larger study[30].In addition,the mean constipation severity-scores correlated directly with the concentration of methane detected on LBT in a study of87IBS patients [31 ].Furthermore,improvement of symptoms for patients with constipation-predominant IBS correlated with a reduction in methane production by neomycin [32].Methane is a biologically active gas that is capable of slowing intestinal transit by shifting the pattern of moti-lity from peristaltic to nonperistaltic[33].In a recent RCT[34 ],87IBS patients were given either rifaximin,a12Gastrointestinal infectionsnonabsorbed oral antibiotic that acted primarily in the small intestine,or placebo.In this study,symptom improvement persisted through the entire10-week obser-vation period following discontinuation of the10-day antibiotic treatment.Since symptom-directed treatment rapidly disappears upon cessation of treatment,such sustained improvement is only possible if the treatment were to be directed,instead,at the underlying cause of the symptoms of IBS and that cause were to be an antibiotic-sensitive mechanism such as SIBO.The relationship between SIBO and intestinal motility was supported by thefinding of reduced frequency of cycling of interdiges-tive motility in patients with IBS[35].Impaired intestinal motility may be a key element in the loss of containment of the microflora,resulting in SIBO.The relationship between acute gastroenteritis,SIBO and IBS can be understood by considering the activation of host immunity by microbes and symptoms as con-sequences of immune activation.An additional piece of evidence supporting the idea of altered gut microbiota is the histologicalfinding of immune activation in both IBS patients with a history of acute gastroenteritis and in IBS patients without such history[36].In animal models, infection of the gastrointestinal tract by nematodes resulted in an alteration of the intestinal myenteric neurons,suggesting an additional mechanism for symptoms in IBS patients[37].Gut microbes and intestinal immune response in inflammatory bowel disease Gastrointestinal inflammation overall is one of the most important factors that influence the quantity and quality of human intestinalflora.This interaction is illustrated by inflammatory bowel disease(IBD).For example,the dominant bacterialflora in patients with IBD differs from healthy patients;similarly,the dominant bacterialflora in patients with ulcerative colitis differs from those diagnosed with Crohn’s disease[38].Differences in microbiota were also found contrasting the bacteria isolated from mucosal biopsies of inflamed versus noninflamed tissue of newly diagnosed and untreated patients[39 ].The contribution of an abundance or reduction of bacteria such as those from the genus Clostridium or the phylum Bacteroidetes in the pathogenesis of these diseases remains to be established. The microflora of IBD patients produces greater amounts of metabolic products(e.g.ammonia and short-chain fatty acids)than the microflora of healthy controls[40].The microflora isolated from inflamed mucosa of IBD patients was also found to trigger the production of interleukin (IL)-12,interferon-g and IL-10,which are important mediators of inflammation in IBD[41].Similarly, increased T-cell response to bacterial antigens has been reported[42].Perhaps the strongest argument for the role of commensal gut microbes in IBD is that researchers were unable to demonstrate the development of colitis in knockout mouse models of IBD when the animals were kept germ free.Specifically,even IL-10 knockout mice would not develop their usual severe intestinal inflammation if raised in a germ-free environ-ment[43].Probiotic organisms and the microflora itself have the ability to shift the inflammatory response in favor of the host;bacteria such as Bifidobacterium bifidum and Lac-tobacillus spp.have been shown to suppress T-cell responses in both an IBD animal model and in patients well as[44 ,45].A recent Cochrane review[46 ],however, suggested that probiotics did not have a statistically significant effect in maintaining remission in Crohn’s disease patients.The use of probiotics has also been investigated in the setting of IBS in several RCTs[47], with promising results reported by O’Mahony et al.[48] using B.infantis.Small intestinal bacterial overgrowth and bacterial translocation in hepatic encephalopathySIBO was diagnosed by abnormal gas excretion using the glucose breath test in more than30%of cirrhotic patients [49–51].Prevalence of spontaneous bacterial peritonitis (SBP)was higher in patients with SIBO,suggesting a causative relationship for this altered state of gut micro-biota[49,50].Another study,which used culture of jeju-nal secretions for the diagnosis of SIBO,reported a60% prevalence of SIBO in70patients with cirrhosis;how-ever,this study did notfind an increased risk of SBP[52]. SIBO was found more frequently in rats with cirrhosis and bacterial translocation(93%)than rats with cirrhosis with-out bacterial translocation(33%)[53].Molecular studies in cirrhotic rats with SBP showed that the bacteria collected from mesenteric lymph nodes resulting from bacterial translocation were identical to that collected from asciticfluid[54].Although a human study failed to show the same relationship between bacterial transloca-tion and SIBO,this may be a consequence of the diffi-culty in obtaining lymph node biopsies from different lymph nodes in humans or to the routine practice of administering antibiotics prior to any surgical procedure [55].Norfloxacin,a poorly absorbed oral quinolone,was found to decrease bacterial translocation in rats with cirrhosis[56].Accordingly,norfloxacin and trimetho-prim–sulfamethoxazole were also effective in reducing the incidence of SBP in patients with cirrhosis[57]. Changing the composition of microflora can affect minimal hepatic encephalopathy(MHE),one of the most common complications in patients with cirrhosis.Bacterial over-growth occurs more frequently in patients with cirrhosis and MHE,compared with patients with cirrhosis but Intestinal microbial flora and human disease Othman et al.13without MHE.Furthermore,these patients have higher concentrations of pathogenic Escherichia coli and Staphylococcus spp.among their fecalflora.A combination of probiotics and prebiotics reduced these pathogenic bacteria,increased nonurease-producing Lactobacillus spp.and reversed MHE in50%of the patients[58]. Increasing the Bifidobacterium spp.count in the intestinal flora by administration of probiotics resulted in normal-ization of the fecal pH and decreased ammonia production in patients with cirrhosis,demonstrating the effectiveness of this probiotic to alter the intestinal microflora[59]. Bacterial antigens and hypersensitivity infibromyalgiaAnimal studies suggest a relationship between bacterial toxins and hypersensitivity.In a rat model,exposure to endotoxin resulted in local inflammation and hyperalgesia [60].Similarly,exposure to lipopolysaccharide induced visceral hypersensitivity in rats[61].Although the mech-anism of endotoxin-induced hyperalgesia is not completely understood,a recent animal study demonstrated that exposure to endotoxin increased the production of prosta-glandins and simultaneously decreased nitrous oxide production,resulting in inflammatory hyperalgesia[62]. Fibromyalgia,a condition of musculoskeletal hypersensi-tivity,provides us with a fascinating model on the link between gut bacteria and somatic hypersensitivity. Between30and75%of patients withfibromyalgia also have symptoms meeting the criteria for IBS[63].Somatic hypersensitivity was demonstrated in IBS andfibromyal-gia patients,suggesting that somatic hypersensitivity could be a common feature of the two disorders[64].The role of gut microbes infibromyalgia is suggested by thefinding that of42patients with the condition,all of them tested positive for hydrogen/methane production,as determined by LBT,afinding similar to a previous study in IBS in which84%of patients had an abnormal LBT[27,65]. These observations suggest that SIBO is a common feature in both disorders and that altered gut microbiota in SIBO may play a role in the induction of somatic or visceral hypersensitivity,with affected patients meeting the diag-nostic criteria for IBS,fibromyalgia or both disorders[65]. Gut bacteria and abnormal intestinal permeability in burn injuryAnimal studies have long established that burns or ther-mal injury caused an increase in bacterial translocation [66,67].Burn injuries induce epithelial apoptosis leading to atrophy of the intestinal mucosa followed by bacterial translocation[68].What is observed is an‘imbalance’in the microflora following thermal injury in rats with decreased proportions of Bifidobacterium spp.relative to the abundance of Gram-negative organisms(e.g.E.coli),followed by bacterial translocation and sepsis[69,70]. Most notable was that animals supplemented with oral Bifidobacterium spp.had a decreased incidence of bac-terial translocation[69].Increased intestinal permeability or leaky gut is also more common among burn victims[71].The severity of the burn injury was found to directly correlate with the degree of increased intestinal permeability[72]. Although it was demonstrated in animal models that bacteria translocate to mesenteric lymph nodes and enter the circulation through portal blood[70],a prospective human trial failed to detect a significant level of bacteria, bacterial endotoxin or inflammatory markers in the portal circulation of patients with major trauma in the presence of inflammatory-mediated lung injury[73].Thisfinding led to the recent gut–lymph hypothesis,which argues that endothelial permeability is selectively higher in the mesenteric lymph nodes and that portal circulation passes inflammatory markers via the thoracic duct to the lung rather than through the liver,causing acute lung injury[74].This hypothesis is further supported by the prevention of acute lung injury in posthemorrhagic rats by ligation of the mesenteric lymphatic system[75]. ConclusionThe human microflora has a significant impact on health and human disease,far more than ever realized.The host response to SIBO and bacterial translocation may explain the clinicalfindings of several pathological conditions. Recognizing the interactive nature of host and gutflora is vital to the diagnosis and treatment of these disorders. AcknowledgementDr Lin acknowledges with gratitude the support of the Jill and Tom Barad Family Fund.References and recommended readingPapers of particular interest,published within the annual period of review,have been highlighted as:of special interestof outstanding interestAdditional references related to this topic can also be found in the Current World Literature section in this issue(pp.76–77).1Benno Y,Sawada K,Mitsuoka T.The intestinal microflora of infants:composi-tion of fecalflora in breast-fed and bottle-fed infants.Microbiol Immunol1984;28:975–986.2Stark P,Lee A.The microbial ecology of the large bowel of breast-fed and formula-fed infants during thefirst year of life.J Med Microbiol1982;15:189–203.3Gorbach S,Bengt E.Gustafsson memorial lecture:function of the normal human microflora.Scand J Infect Dis1986;49:17–30.4Ouwehand A,Isolauri E,Salminen S.The role of the intestinal microflora for the development of the immune system in early childhood.Eur J Nutr2002;41:I32–I37.5Turner J.Molecular basis of epithelial barrier regulation:from basic mech-anisms to clinical application.Am J Pathol2006;169:1901–1909.6Gasbarrini G,Montalto M.Structure and function of tight junctions:role in intestinal barrier.Ital J Gastroenterol Hepatol1999;31:481–488.14Gastrointestinal infections7Nusrat A,Turner J,Madara J.Molecular physiology and pathophysiology of tight junctions.IV:Regulation of tight junctions by extracellular stimuli: nutrients,cytokines,and immune cells.Am J Physiol Gastrointest Liver Physiol 2000;279:G851–G857.8Li Y,Newton T,Weisbrodt N,Moody F.Intestinal migrating myoelectric complexes in rats with acute pancreatitis and bile duct ligation.J Surg Res 1993;55:182–187.9Lee H,Pimentel M.Bacteria and irritable bowel syndrome:the evidence for small intestinal bacterial overgrowth.Curr Gastroenterol Rep2006;8:305–311. 10Lin HC.Small intestinal bacterial overgrowth:a framework for understanding irritable bowel syndrome.JAMA2004;292:852–858.11Moody F,Haley-Russell D,Muncy D.Intestinal transit and bacterial transloca-tion in obstructive pancreatitis.Dig Dis Sci1995;40:1798–1804.12Van Felius I,Akkermans L,Bosscha K,et al.Interdigestive small bowel motility and duodenal bacterial overgrowth in experimental acute pancreatitis.Neurogastroenterol Motil2003;15:267–276.13Mifkovic A,Pindak D,Daniel I,Pechan J.Septic complications of acute pancreatitis.Bratisl Lek Listy2006;107:296–313.14van Minnen L,Blom M,Timmerman H,et al.The use of animal models to study bacterial translocation during acute pancreatitis.J Gastrointest Surg2007;11:682–689.15Arendt T,Wendt M,Olszewski M,et al.Cerulein-induced acute pancreatitis in rats:does bacterial translocation occur via a transperitoneal pathway?Pancreas1997;15:291–296.16Ammori BJ,Leeder PC,King RF,et al.Early increase in intestinal permeability in patients with severe acute pancreatitis:correlation with endotoxemia,organ failure,and mortality.J Gastrointest Surg1999;3:252–262.17Penalva J,Martinez J,Laveda R,et al.A study of intestinal permeability in relation to the inflammatory response and plasma endocab IgM levels in patients with acute pancreatitis.J Clin Gastroenterol2004;38:512–517. 18de Madaria E,Martinez J,Lozano B,et al.Detection and identification of bacterial DNA in serum from patients with acute pancreatitis.Gut2005;54:1293–1297.19Bassi C,Larvin M,Villatoro E.Antibiotic therapy for prophylaxis against infection of pancreatic necrosis in acute pancreatitis.Cochrane Database Syst Rev2003;(15):CD002941.20Mazaki T,Ishii Y,Takayama T.Meta-analysis of prophylactic antibiotic use in acute necrotizing pancreatitis.Br J Surg2006;93:674–684.21 Spiller R.Role of infection in irritable bowel syndrome.J Gastroenterol2007; 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102:837–841.This study extended previous work showing that breath methane concentration is correlated with constipation.32Pimentel M,Chatterjee S,Chow E,et al.Neomycin improves constipation-predominant irritable bowel syndrome in a fashion that is dependent on the presence of methane gas:subanalysis of a double-blind randomized controlled study.Dig Dis Sci2006;51:1297–1301.33Pimentel M,Lin H,Enayati P,et al.Methane,a gas produced by enteric bacteria,slows intestinal transit and augments small intestinal contractile activity.Am J Physiol Gastrointest Liver Physiol2006;290:G1089–G1095.34Pimentel M,Park S,Mirocha J,et al.The effect of a nonabsorbed oral antibiotic (rifaximin)on the symptoms of the irritable bowel syndrome:a randomized trial.Ann Intern Med2006;145:557–563.In contrast to treatments directed at symptoms for which the beneficial effect disappears upon withdrawal of therapy,this study showed that a short course of gut-directed antibiotic therapy led to sustained clinical benefit even after cessation of treatment for the entire monitoring period of10weeks.35Pimentel M,Soffer EE,Chow EJ,Lin HC.Lower frequency of MMC is found in IBS subjects with abnormal lactulose breath test suggesting bacterial over-growth.Dig Dis Sci2002;47:2639–2643.36Chadwick V,Chen W,Shu D,et al.Activation of the mucosal immune system in irritable bowel syndrome.Gastroenterology2002;122:1778–1783.37Palmer J,Wong-Riley M,Sharkey K.Functional alterations in jejunal myenteric neurons during inflammation in nematode-infected guinea pigs.Am J Physiol 1998;275:G922–G935.38Sokol H,Seksik P,Rigottier-Gois L,et al.Specificities of the fecal microbiota in inflammatory bowel disease.Inflamm Bowel Dis2006;12:106–111.39Bibiloni R,Mangold M,Madsen K,et al.The bacteriology of biopsies differs between newly diagnosed,untreated,Crohn’s disease and ulcerative colitis patients.J Med Microbiol2006;55:1141–1149.By showing that the mucosa-associated microbiota correlates with clinical diag-nosis and disease state,this study provides further support for the role of commensal gut bacteria in inflammatory bowel disease.40van Nuenen M,Venema K,van der Woude J,Kuipers E.The metabolic activity of fecal microbiota from healthy individuals and patients with inflammatory bowel disease.Dig Dis Sci2004;49:485–491.41Duchmann R,Kaiser I,Hermann E,et al.Tolerance exists towards resident intestinalflora but is broken in active inflammatory bowel disease(IBD).Clin Exp Immunol1995;102:448–455.42Cong Y,Brandwein S,McCabe R,et al.CD4þT cells reactive to enteric bacterial antigens in spontaneously colitic C3H/HeJBir mice:increased T helper cell type1response and ability to transfer disease.J Exp Med 1998;187:855–864.43Sellon R,Tonkonogy S,Schultz M,et al.Resident enteric bacteria are necessary for development of spontaneous colitis and immune system activation in interleukin-10-deficient mice.Infect Immun1998;66:5224–5231.44Kim N,Kunisawa J,Kweon M,et al.Oral feeding of Bifidobacterium bifidum (BGN4)prevents CD4(þ)CD45RB(high)T cell-mediated inflammatory bowel disease by inhibition of disordered T cell activation.Clin Immunol 2007;123:30–39.This study showed that a specific probiotic was protective in a T-cell transfer inflammatory bowel disease model.This protective effect of probiotic was asso-ciated with fewer CD4þT cells and suppression of proinflammatory cytokine production.45Matsumoto S,Watanabe N,Imaoka A,Okabe Y.Preventive effects of Bifidobacterium-and Lactobacillus-fermented milk on the development of inflammatory bowel disease in senescence-accelerated mouse P1/Yit strain mice.Digestion2001;64:92–99.46Rolfe V,Fortun P,Hawkey C,Bath-Hextall F.Probiotics for maintenance of remission in Crohn’s disease.Cochrane Database Syst Rev2006;(18): CD004826.This review found that the seven controlled trials testing the effect of probiotics have not shown any benefit in Crohn’s disease and that the studies may have lacked sufficient statistical power to demonstrate an effect.47Othman M,Roy P.Probiotic in irritable bowel syndrome:a systematic review.Am J Gastroenterol2005;100:S32.48O’Mahony l,McCarthy J,Kelly P,et ctobacillus and Bifidobacterium in irritable bowel syndrome:symptom response and relationship to cytokine profiles.Gastroenterology2005;128:783–785.49Morencos F,de las Heras Castano G,Martin Ramos L,et al.Small bowel bacterial overgrowth in patients with alcoholic cirrhosis.Dig Dis Sci1995;40:1252–1256.50Casafont Morencos F,de las Heras Castano G,Martin Ramos L,et al.Small bowel bacterial overgrowth in patients with alcoholic cirrhosis.Dig Dis Sci 1996;41:552–556.Intestinal microbial flora and human disease Othman et al.15。
扩展影响因子期刊分类期刊分类代码期刊名称扩展总被引频工程与技术科学基础学科E01CT理论与应用研究5440.715经济学综合L01WTO经济导刊186 3.158社会科学师范大学学报H03阿坝师范学院学报3130.193国际政治学、外交学M04阿拉伯世界研究2990.943肿瘤学D29癌变·畸变·突变4750.444肿瘤学D29癌症（英文版）2033 1.586肿瘤学D29癌症进展1096 1.197肿瘤学D29癌症生物学与医学（英文版 ）180 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1.613预防医学与公共卫生学综D31安徽预防医学杂志5530.403成人教育学、职业技术教P05安徽职业技术学院学报2040.23中医药大学学报D38安徽中医药大学学报16220.935社会科学综合大学学报H02安康学院学报3790.174社会科学师范大学学报H03安庆师范学院学报（社会科学版）6480.191自然科学师范大学学报A03安庆师范学院学报（自然科学版）4370.338安全科学技术E40安全5060.471安全科学技术E40安全、健康和环境6210.275电气工程E15安全与电磁兼容1720.201安全科学技术E40安全与环境工程14960.902安全科学技术E40安全与环境学报30360.853教育学综合P01安顺学院学报3800.203工程技术大学学报E02安阳工学院学报5470.268社会科学师范大学学报H03安阳师范学院学报5080.255建筑科学与技术E31安装5970.471林学C07桉树科技2610.524生物学基础学科B13氨基酸和生物资源7210.525冶金工程技术E11鞍钢技术3390.228社会科学师范大学学报H03鞍山师范学院学报4600.272中医学D37按摩与康复医学23740.303社会学综合N01八桂侨刊1060.114医学综合D01白求恩医学杂志2383 1.026肿瘤学D29白血病·淋巴瘤6590.464社会科学综合大学学报H02百色学院学报3630.181经济学综合L01办公室业务44600.564计算机科学技术E22办公自动化1620.424电子技术E19半导体光电6010.276电子技术E19半导体技术6080.298电子技术E19半导体学报（英文版）10540.545教育学综合P01蚌埠学院学报1940.204医药大学学报D02蚌埠医学院学报3595 1.112冶金工程技术E11包钢科技3530.14医学综合D01包头医学5210.517医药大学学报D02包头医学院学报22210.66成人教育学、职业技术教P05包头职业技术学院学报1910.254工程与技术科学基础学科E01包装工程6575 1.449工程与技术科学基础学科E01包装世界4740.329工程与技术科学基础学科E01包装学报3550.993食品科学技术E30包装与食品机械896 1.417冶金工程技术E11宝钢技术5170.213冶金工程技术E11宝钢技术研究（英文版）300.065社会科学综合大学学报H02宝鸡文理学院学报（社会科学版）3820.211自然科学综合大学学报A02宝鸡文理学院学报（自然科学版）1970.353应用化学工程E26宝石和宝石学杂志3010.4教育学综合P01保定学院学报4110.263预防医学与公共卫生学综D31保健医学研究与实践6880.694社会科学综合大学学报H02保山学院学报2540.165农业工程E05保鲜与加工967 1.044财政学、金融学、保险学L10保险研究1705 1.252经济大学学报L02保险职业学院学报3070.282大气科学B08暴雨灾害899 1.47兵器科学与技术E28爆破1390 1.124兵器科学与技术E28爆破器材3940.375兵器科学与技术E28爆炸与冲击14630.693畜牧、兽医科学C08北方蚕业2160.306法学综合M05北方法学6310.924工程技术大学学报E02北方工业大学学报2410.22园艺学C04北方果树6040.202交通运输工程E34北方交通15550.507财政学、金融学、保险学L10北方金融3290.39经济学综合L01北方经济1138 1.554工商业经济学L08北方经贸22680.31社会科学综合H01北方论丛5440.223社会科学综合大学学报H02北方民族大学学报（哲学社会科学版6260.403农业综合C01北方农业学报15450.307农艺学C03北方水稻6500.376历史学K08北方文物5610.166中国文学K04北方文学（下旬刊）6260.035中国文学K04北方文学（中旬刊）1830.029药学D36北方药学55820.686艺术学K06北方音乐19060.199园艺学C04北方园艺71820.552社会科学综合大学学报H02北华大学学报（社会科学版）5570.346自然科学综合大学学报A02北华大学学报（自然科学版）10330.82航空、航天科学技术E38北华航天工业学院学报2600.306经济大学学报L02北京财贸职业学院学报1700.418测绘科学技术E07北京测绘9070.623自然科学综合大学学报A02北京城市学院学报4090.423教育学综合P01北京大学教育评论1582 2.406医药大学学报D02北京大学学报（医学版）3051 1.636社会科学综合大学学报H02北京大学学报（哲学社会科学版）3421 1.039自然科学综合大学学报A02北京大学学报（自然科学版）2258 1.109档案学、博物馆学N08北京档案7340.811外国语言学K03北京第二外国语学院学报13790.645艺术学K06北京电影学院学报7580.886自然科学综合大学学报A02北京电子科技学院学报1630.301工程技术大学学报E02北京服装学院学报（自然科学版）1500.2社会科学综合大学学报H02北京工商大学学报（社会科学版）1293 1.624工程技术大学学报E02北京工业大学学报17240.622社会科学综合大学学报H02北京工业大学学报（社会科学版）3660.591教育学综合P01北京工业职业技术学院学报5030.452政治大学学报M02北京行政学院学报8090.675航空、航天科学技术E38北京航空航天大学学报24450.571社会科学综合大学学报H02北京航空航天大学学报（社会科学版6520.47社会科学综合大学学报H02北京化工大学学报（社会科学版）2180.385化学工程综合E23北京化工大学学报（自然科学版）8600.401建筑科学与技术E31北京建筑大学学报5630.847工程技术大学学报E02北京交通大学学报11550.505社会科学综合大学学报H02北京交通大学学报（社会科学版）743 1.361学前教育学、普通教育学P03北京教育（高教版）8170.686学前教育学、普通教育学P03北京教育（普教版）291 2.647社会科学综合大学学报H02北京教育学院学报（社会科学版）3130.355自然科学综合大学学报A02北京教育学院学报（自然科学版）2480.588政治大学学报M02北京经济管理职业学院学报2550.686法学综合M05北京警察学院学报4510.486社会科学综合大学学报H02北京科技大学学报（社会科学版）6030.577口腔医学D24北京口腔医学6180.675政治大学学报M02北京劳动保障职业学院学报2160.522工程技术大学学报E02北京理工大学学报19680.493社会科学综合大学学报H02北京理工大学学报（社会科学版）11350.993工程技术大学学报E02北京理工大学学报（英文版）1850.1社会科学综合大学学报H02北京联合大学学报（人文社会科学版524 1.281自然科学综合大学学报A02北京联合大学学报（自然科学版）4740.566林学C07北京林业大学学报3641 1.04社会科学综合大学学报H02北京林业大学学报（社会科学版）5740.703农业大学学报C02北京农学院学报7620.662农业综合C01北京农业44770.439农业大学学报C02北京农业职业学院学报3780.366交通运输工程E34北京汽车2140.225政治学综合M01北京青年研究3100.592社会科学综合H01北京社会科学10630.948生物医学工程学E06北京生物医学工程4700.498社会科学师范大学学报H03北京师范大学学报（社会科学版）3042 1.431自然科学师范大学学报A03北京师范大学学报（自然科学版）10230.456政治大学学报M02北京石油管理干部学院学报1680.21石油天然气工程E17北京石油化工学院学报2270.33政治大学学报M02北京市工会干部学院学报1020.235水利工程E33北京水务4380.358体育科学P07北京体育大学学报7678 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2.043经济学综合L01财经研究3666 2.859财政学、金融学、保险学L10财贸经济4031 2.803财政学、金融学、保险学L10财贸研究1358 1.96财政学、金融学、保险学L10财务研究75会计学、审计学L05财务与会计1804 3.045财政学、金融学、保险学L10财务与金融4770.543经济学综合L01财政研究2616 1.695矿山工程技术E10采矿技术12590.63矿山工程技术E10采矿与安全工程学报3988 1.903新闻学与传播学N05采写编2270.4社会学综合N01残疾人研究2820.622畜牧、兽医科学C08蚕桑茶叶通讯2320.351畜牧、兽医科学C08蚕桑通报2700.39畜牧、兽医科学C08蚕学通讯1320.261畜牧、兽医科学C08蚕业科学13110.63社会科学师范大学学报H03沧州师范学院学报3140.167中国文学K04曹雪芹研究65草原学C09草地学报2702 1.078畜牧、兽医科学C08草食家畜5910.618草原学C09草业科学5068 1.857草原学C09草业学报5778 2.784畜牧、兽医科学C08草业与畜牧6450.286历史学K08草原文物2230.368草原学C09草原与草坪11250.716畜牧、兽医科学C08草原与草业3080.49测绘科学技术E07测绘3460.427地理学B10测绘地理信息9230.902测绘科学技术E07测绘工程1597 1.333测绘科学技术E07测绘技术装备3020.4测绘科学技术E07测绘科学36430.852测绘科学技术E07测绘科学技术学报9780.686测绘科学技术E07测绘通报4650 1.336测绘科学技术E07测绘学报3732 1.86测绘科学技术E07测绘与空间地理信息33590.72石油天然气工程E17测井技术17430.49航空、航天科学技术E38测控技术19020.439工程与技术科学基础学科E01测试技术学报4730.28机械制造工艺与设备E13测试科学与仪器460.163食品科学技术E30茶业通报3670.256农艺学C03茶叶5960.691园艺学C04茶叶科学1758 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1.09中医药大学学报D38成都中医药大学学报11730.793成人教育学、职业技术教P05成人教育20390.627工程与技术科学基础学科E01成组技术与生产现代化1250.327石油天然气工程E17承德石油高等专科学校学报3240.31医药大学学报D02承德医学院学报10210.521建筑科学与技术E31城建档案803 1.578经济学综合L01城市4850.371交通运输工程E34城市道桥与防洪26350.476地质学B11城市地理26750.588地质学B11城市地质2610.687建筑科学与技术E31城市发展研究4430 1.706公路运输E35城市公共交通1190.184经济学综合L01城市观察4200.591经济学综合L01城市管理与科技3430.408建筑科学与技术E31城市规划56283建筑科学与技术E31城市规划学刊3569 3.216铁路运输E36城市轨道交通研究24800.763建筑科学与技术E31城市环境设计245 1.903生态学B14城市环境与城市生态9570.711建筑科学与技术E31城市建设理论研究（电子版）285800.075建筑科学与技术E31城市建筑79160.244公路运输E35城市交通1099 1.2建筑科学与技术E31城市开发281建筑科学与技术E31城市勘测12910.516动力工程E14城市燃气3800.538国民经济学、管理经济学L04城市问题2595 1.201社会科学综合大学学报H02城市学刊3240.247安全科学技术E40城市与减灾102 1.692建筑科学与技术E31城市住宅3810.85建筑科学与技术E31城乡建设831 3.957建筑科学与技术E31城镇供水3120.319教育学综合P01池州学院学报6000.235社会科学综合大学学报H02赤峰学院学报（哲学社会科学版）16190.191自然科学综合大学学报A02赤峰学院学报（自然科学版）54990.486社会学综合N01赤子45980.647新闻学与传播学N05出版参考51812.769新闻学与传播学N05出版发行研究15130.849新闻学与传播学N05出版广角11190.623新闻学与传播学N05出版科学5460.564新闻学与传播学N05出版与印刷790.533社会科学综合大学学报H02滁州学院学报5030.201成人教育学、职业技术教P05滁州职业技术学院学报2130.284能源科学综合E16储能科学与技术2840.808社会科学师范大学学报H03楚雄师范学院学报4920.311畜牧、兽医科学C08畜牧兽医科技信息17690.906畜牧、兽医科学C08畜牧兽医学报24660.667畜牧、兽医科学C08畜牧兽医杂志11130.287畜牧、兽医科学C08畜牧与生物技术杂志（英文版）1370.596畜牧、兽医科学C08畜牧与兽医22800.47畜牧、兽医科学C08畜牧与饲料科学24410.427畜牧、兽医科学C08畜禽业13570.22医药大学学报D02川北医学院学报1274 1.079新闻学与传播学N05传播与版权6520.533政治学综合M01传承6250.129计算机科学技术E22传动技术840.087电子技术E19传感技术学报3114 1.407计算机科学技术E22传感器世界3470.206电子技术E19传感器与微系统27330.619新闻学与传播学N05传媒922 1.307新闻学与传播学N05传媒观察5820.606新闻学与传播学N05传媒评论463 1.356感染性疾病学、传染病学D13传染病信息954 1.224水路运输E37船舶4030.318工程与技术科学基础学科E01船舶标准化工程师700.158工程与技术科学基础学科E01船舶标准化与质量280.246水路运输E37船舶工程9550.433水路运输E37船舶力学10610.483水路运输E37船舶设计通讯940.186水路运输E37船舶物资与市场42水路运输E37船舶与海洋工程2930.526水路运输E37船舶与海洋工程学报（英文版）1640.196水路运输E37船舶职业教育98水路运输E37船电技术4610.192水路运输E37船海工程9340.372社会科学综合H01船山学刊2940.206烧伤外科学、整形外科学D19创伤外科杂志1894 1.287临床医学综合D05创伤与急危重病医学307 1.148临床医学综合D05创伤与急诊电子杂志910.536社会科学综合H01创新3270.371自然科学综合A01创新科技5810.23教育学综合P01创新人才教育660.537教育学综合P01创新与创业教育9570.809社会学综合N01创意设计源600.326社会学综合N01创意与设计1930.348经济学综合L01创造87中国文学K04创作与评论3530.254数学B01纯粹数学与应用数学2730.247化学工程综合E23纯碱工业1440.138语言学综合K01辞书研究4260.186临床诊断学D06磁共振成像1175 2.212信息与系统科学相关工程E03磁性材料及器件4400.399化学B05催化学报25040.889水利工程E33大坝与安全3230.244化学工程综合E23大氮肥2620.21地球科学综合B07大地测量与地球动力学21880.663测绘科学技术E07大地测量与地球动力学（英文版）670.387地质学B11大地构造与成矿学2024 1.31电气工程E15大电机技术4980.329农艺学C03大豆科技4920.681农艺学C03大豆科学18640.72交通运输工程E34大功率变流技术2320.4中国文学K04大观3100.058社会学综合N01大家689 2.1保健医学D07大家健康（下旬版）57160.286保健医学D07大家健康（中旬版）35030.221社会科学综合H01大科技22480.099社会科学综合大学学报H02大理大学学报9790.412教育学综合P01大连大学学报5790.239政治学综合M01大连干部学刊1410.174工程技术大学学报E02大连工业大学学报5490.414水路运输E37大连海事大学学报7470.483社会科学综合大学学报H02大连海事大学学报（社会科学版）4440.35水产学C10大连海洋大学学报11840.81交通运输工程E34大连交通大学学报5140.352教育学综合P01大连教育学院学报4580.341工程技术大学学报E02大连理工大学学报13910.776社会科学综合大学学报H02大连理工大学学报（社会科学版）6670.94教育学综合P01大连民族大学学报4330.311医药大学学报D02大连医科大学学报9860.818经济学综合L01大陆桥视野6420.152农艺学C03大麦与谷类科学3350.405大气科学B08大气和海洋科学快报（英文版）2390.295大气科学B08大气科学4505 1.668大气科学B08大气科学进展（英文版）15530.759大气科学B08大气科学学报1934 1.177大气科学B08大气与环境光学学报2690.376社会科学综合H01大庆社会科学3860.209社会科学师范大学学报H03大庆师范学院学报4590.297石油天然气工程E17大庆石油地质与开发2357 1.046计算机科学技术E22大数据121艺术学K06大舞台24040.265机械制造工艺与设备E13大型铸锻件2670.205高等教育学P04大学（研究版）5880.455化学B05大学化学11080.894高等教育学P04大学教育24510.569高等教育学P04大学教育科学1228 1.12数学B01大学数学10350.435图书馆学、文献学N06大学图书馆学报2921 3.351图书馆学、文献学N06大学图书情报学刊7800.832物理学B04大学物理10370.319高等教育学P04大学物理实验11150.772自然科学综合A01大众科技24710.308计算机科学技术E22单片机与嵌入式系统应用10940.451水产学C10淡水渔业12670.658兵器科学与技术E28弹道学报6910.574兵器科学与技术E28弹箭与制导学报14820.272高聚物工程E24弹性体7070.471生物学基础学科B13蛋白质与细胞3790.853化学工程综合E23氮肥技术1330.14中国文学K04当代107财政学、金融学、保险学L10当代财经2494 1.628畜牧、兽医科学C08当代畜禽养殖业6360.59新闻学与传播学N05当代传播1581 1.012信息与系统科学相关工程E03当代电视6690.573艺术学K06当代电影25850.915法学综合M05当代法学2076 2.402社会科学综合H01当代韩国1370.364护理学D30当代护士（上旬刊）7030.762护理学D30当代护士（下旬刊）56520.724护理学D30当代护士（中旬刊）58680.667化学工程综合E23当代化工17580.406会计学、审计学L05当代会计4310.447教育学综合P01当代继续教育3910.434教育学综合P01当代教师教育2990.526教育学综合P01当代教育科学25970.942教育学综合P01当代教育理论与实践19460.504教育学综合P01当代教育论坛3233 1.327教育学综合P01当代教育实践与教学研究（电子刊）15960.265教育学综合P01当代教育与文化4600.603经济学综合L01当代经济41880.418管理学F01当代经济管理1506 1.618经济学综合L01当代经济科学1371 1.585经济学综合L01当代经济研究12530.952矿山工程技术E10当代矿工67生态农业经济学L06当代农村财经281 2.941农业工程E05当代农机2880.351社会学综合N01当代青年研究9990.682石油天然气工程E17当代石油石化4170.276国际政治学、外交学M04当代世界5490.969国际政治学、外交学M04当代世界社会主义问题2270.449国际政治学、外交学M04当代世界与社会主义12070.94水产学C10当代水产2290.96体育科学P07当代体育科技55300.389外国文学K05当代外国文学5810.45语言学综合K01当代外语研究6780.642中国文学K04当代文坛6450.318艺术学K06当代戏剧1420.411语言学综合K01当代修辞学9360.992国际政治学、外交学M04当代亚太879 2.541医学综合D01当代医学27494 1.068医学综合D01当代医药论丛92310.714语言学综合K01当代语言学10060.869中国文学K04当代长篇小说选刊21成人教育学、职业技术教P05当代职业教育10760.548历史学K08当代中国史研究4750.5中国文学K04当代作家评论11660.471档案学、博物馆学N08档案3720.458档案学、博物馆学N08档案管理9320.545档案学、博物馆学N08档案记忆2110.349档案学、博物馆学N08档案时空2130.609档案学、博物馆学N08档案学通讯2089 1.49档案学、博物馆学N08档案学研究1441 1.45档案学、博物馆学N08档案与建设8130.66政治学综合M01党的生活（黑龙江）260.304政治学综合M01党的文献5610.708政治学综合M01党建563政治学综合M01党史博采（理论版）4250.332政治学综合M01党史文苑（纪实版）44政治学综合M01党史文苑（学术版）4400.168政治学综合M01党史研究与教学2860.41政治学综合M01党史纵览39政治学综合M01党政干部论坛1770.3政治学综合M01党政干部学刊3610.264政治学综合M01党政论坛294 3.444政治学综合M01党政研究3750.651航空、航天科学技术E38导弹与航天运载技术5250.316测绘科学技术E07导航定位学报1980.581测绘科学技术E07导航定位与授时200.121航空、航天科学技术E38导航与控制930.159社会科学综合H01道德与文明9480.544交通运输工程E34道路交通与安全2470.4社会科学综合H01德国研究380 1.667自然科学综合大学学报A02德州学院学报3610.212电子技术E19灯与照明2530.268物理学B04等离子体科学和技术（英文版）4440.4环境科学技术及资源科学E39低碳世界72260.405机械制造工艺与设备E13低温工程5530.437建筑科学与技术E31低温建筑技术15280.247物理学B04低温物理学报1560.188物理学B04低温与超导6490.311物理学B04低温与特气2370.268地质学B11地层学杂志11780.99财政学、金融学、保险学L10地方财政研究875 1.019民族学与文化学N04地方文化研究600.182政治大学学报M02地方治理研究2340.33测绘科学技术E07地矿测绘3310.591学前教育学、普通教育学P03地理教育3420.714地理学B10地理科学7076 2.907地理学B10地理科学进展6034 4.034测绘科学技术E07地理空间信息16850.551地理学B10地理信息世界8680.957地理学B10地理学报12383 5.112地理学B10地理学报（英文版）867 1.615地理学B10地理研究8655 3.674地理学B10地理与地理信息科学2612 1.31地球科学综合B07地球9730.079地球科学综合B07地球化学26280.825地质学B11地球化学学报（英文版）2180.246地球科学综合B07地球环境学报740.408地球科学综合B07地球科学进展4934 2.218地球科学综合B07地球科学前沿2500.555地球科学综合B07地球科学学刊5080.627地球科学综合B07地球科学与环境学报1154 1.283地球科学综合B07地球科学-中国地质大学学报41072地理学B10地球空间信息科学学报（英文版）1020.073地球物理学B09地球物理学报12217 2.659地球物理学B09地球物理学进展5521 1.209地球科学综合B07地球信息科学学报1669 1.075地球科学综合B07地球学报3291 2.443地球科学综合B07地球与环境14940.949铁路运输E36地下工程与隧道3390.318土木工程E32地下空间与工程学报37631地质学B11地下水13680.244地球科学综合B07地学前缘7438 2.757地理学B10地学前缘（英文版）2550.654地理学B10地域研究与开发3055 1.638地球物理学B09地震9890.758地球物理学B09地震地磁观测与研究8920.338地球物理学B09地震地质2074 1.146地球物理学B09地震工程学报13210.871地球物理学B09地震工程与工程振动24670.766地质学B11地震工程与工程振动（英文版）2390.409地球物理学B09地震学报19980.875地球物理学B09地震学报（英文版）1660.306地球物理学B09地震研究8980.877地质学B11地质科技情报2358 1.048地质学B11地质科学2323 1.068。
2013年高校职称评审有关学术刊物目录 一、2013年仍发在2009-2012年已经公布的不认可刊物目录而未通过评审
二、2013年因在下列11种未经国际新闻出版署批准且专业性、学术性不强刊物发表论文而未获通过评审
三、2013年因在下列33种专业性、学术性不强刊物发表论文而未获通过评审
四、下列8种学报因刊物质量差，已在2011-2012年连续2年建议今后不要在此类刊物发表论文，如2014年仍在该刊发表论文将视为不合格刊物
五、2013年评审中评委认为下列13种学报学术质量低，建议慎重发稿
六、下列7种刊物指定学科申报讲师符合条件。
附1：国家出版总署取缔的197种非法出版刊物和学院认定的不予奖励的刊物名录现将国家新闻出版署最近几年来发布的非法出版物名单发布如下。
按照上级文件精神及学校有关规定，凡在非法出版物上刊发的文章一概无效，不视为个人科研功效，在职称评审进程中不予承认。
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第一批（共计30种）：经国家新闻出版总署审核确认，2004年7月第一批被取缔的利用境外注册刊号在境内非法出版的30种期刊为非法刊物：一、《WTO与中国》ISSN1684-2170CN62-4342/H二、《中华医学论坛》ISSN1684-8977CN42-0125/R3、《中国教育论坛》ISSN1684-9566CN42-0138/H4、《中华之窗》ISSN1606-9056五、《新印刷》ISSN1727-8899六、《纸张行情》ISSN1682-40757、《中国教育与经济论坛》ISSN1728-2462CN43-8816/R八、《中国经济论坛》ISSN1682-119XZS九、《中国经济评论》ISSN1726-959810、《中外新闻》ISSN1607-40251一、《中国社会新闻》ISSN1684-03051二、《中国社会新闻》ISSN1727-596213、《西部太阳能》ISSN1682-119X14、《中国乳品》ISSN1810-12911五、《中国肉食工业》ISSN1810-04651六、《中国烟草企业文化》ISSN1688-518X17、《中外饭馆》ISSN1683-02611八、《国际电子商讯》ISSN1683-54681九、《美丽人生》ISSN1703-572420、《现代华人》国际标准丛刊编号2一、《外经导报》ISSN1683-44532二、《中国城市进展》ISSN1727-804XO23、《中外烟酒茶》ISSN 1683-467424、《美国中华护理》ISSN1543-14792五、《防雷世界》ISSN1727-54152六、《防雷》ISSN1684-484X27、《陶瓷》ISSN1726-28382八、《中国关注》ISSN1009-5071CN11-4461/I2九、《中国关注》ISSN1727-722130、《卫星通信广播电视》ISSN1563-2431第二批：（共计60种）新闻出版总署、全国"扫黄"办2004年11月18日再次发布60种非法报刊为非法出版物，并宣布依法取缔，名单如下：一、《人民权益报》（ISSN1728－7383）；二、《中国法制报》（ISSN1810－1720）；3、《中国模具报》（ISSN1683－0717）；4、《中华教育杂志》（ISSN1684－0445）；五、《中国今世教育杂志》（ISSN1682－7317，CN（HK）NR4069－194／01）；六、《中华教育教学实践与研究杂志》（ISSN1728－7502，CN16－1690／NR）；7、《中国教育理论杂志》（ISSN1683－3767，CN（HK）NR4137－53／02）；八、《中国教育教学研究杂志》（ISSN1726－3018，CN18－4258／H）；九、《中国教育》（ISSN1681－1615，CN·NR37－02）；10、《中国现代教育杂志》（ISSN1682－2706，CN35－3917HK／G）；1一、《中国素质教育理论与实践》（ISSN1728－3531，CN03－3569／G·HK）；1二、《中国教育改革与研究》（ISSN1727－5121，CN（H）39－7869／G）；13、《教学纵横》（ISSN1683－514X，CN（HK）NR4159／87／02）；14、《今世教育》（ISSN1607－2065，CN（HK）NR4064／190／01）；1五、《中华教育教学实践》（ISSN1726－6416，CN03－4383／HK）；1六、《今世素质教育》（ISSN1726－765X，CN03－3313／G·HK）；17、《中国教育研究》（ISSN1727－0405，CN39－7848／／G4）；1八、《中国新教育》（ISSN1727／7167，NR4332／56／03）；1九、《中国高等教育研究杂志》（ISSN1729－5726，CN13－9232／G4）；20、《中国新世纪教育》（ISSN1684－8606，CN39－7618／G）；2一、《中国教育探索》（ISSN1009－5071，CN11－4461／I）；2二、《中华现代医药》（ISSN1681－5572，CN98－0072／HK）；23、《中华医学教育与实践》（ISSN1726－1899，CN（HK）39－7818／R）；24、《中华医学教学与临床》（ISSN1608－6716，CN19－2216／HK）；2五、《中华现代全科医学杂志》（ISSN1680－6344，CN29－3227／R）；2六、《中华现代临床医药杂志》（ISSN1606－4666，CN01－4097／R）；27、《中华医药研究与创新》（ISSN1680－9343，CN31－3927／R）；2八、《中国医药保健》（ISSN1810－363X）；2九、《中国医药》（ISSN1608－3776）；30、《世界医学论坛》（ISSN1726－295X）；3一、《建筑电气资讯》（ISSN1606－9668）；3二、《中国电气》（ISSN1811－4709）；33、《电气设计与设备》（ISSN1727－8171）；34、《电气世界》（ISSN1684－9191）；3五、《照明》（ISSN1729－3979）；3六、《电气＆智能建筑》（ISSN1609－0403）；37、《中国石油瞭望》（ISSN1727－9011）；3八、《触动》（ISSN1810－1216，CN03－0127／H）；3九、《环球消防》（ISSN1726－8869）；40、《中华财富》（ISSN1727－7418）；4一、《今世市长》（ISSN1681－6609）；4二、《中国城市》（ISSN1726－1759）；43、《中外妇女》（ISSN1608－7836）；44、《中外慈善世界》（ISSN1608－7828）；4五、《中国农业产业化》（ISSN1683－3791）；4六、《法制新闻》（ISSN1727－0960）；47、《百姓与法制》（ISSN1728－8703）；4八、《中国法治新闻》（ISSN1727－5989）；4九、《诚信山西》（ISSN1682－119XZs）；50、《PIONEERCHINA创业中国》（ISSN1729－1283）；5一、《中国创新报导》（ISSN1684－3878）；5二、《南方观察》（ISSN1728－2497，CN33－66065／9）；53、《深度新闻》（ISSN1006－0400，CN99（Q）004）；54、《中国经贸》（ISSN1606－8548）；5五、《健康指南》（CN45－0056）；5六、《新旅行TRAVELER》（ISSN1671－6930，CN46－1067／GO）；57、《新旅行VOYAGE》（ISSN1009－6450，CN42－1620／J）；5八、《新地产OFFICE》（ISSN1009－251X，CN23－1447／G2）；5九、《新地产HOUSING》（ISSN1672－5719，CN11－5052／Z）；60、《中国社会报"警视专刊"》（CN11－0021）。
考前思博论坛讲座笔记1、平衡权利与贡献标志性语句特征特征之间的关系①产品、物质、材料、工具、装置、设备②制造方法、使用方法、通讯方法、处理方法及产品特定用途的方法如果需要写方法，会再次对应发明点描述一遍过程2、贡献了的，哪些是主要技术效果例如07年粘结力大小是否写入独权？要考虑三个实施例整体贡献了什么现有技术无撕开部件撕开不见已是贡献了而且粘结力大小在实施例2中不是必须的3、最小拆解原则分层标志性语句：优选例如还可以是另外特别是进一步具体是作为变型更佳……10年真题u型管状电热器写入独权材料没有给出其他变型可知不是发明点，如果不写入得不到材料的支持4、相对于主要技术效果锦上添花—写入从权雪中送炭—写入独权5、特征之间的关系并列关系07年的带状或绳状部件上下位关系下位的肯定要写入从权一般与特殊特殊的肯定要写入从权6、用交底书中其他主题验证是否为区别技术特征08年方法和设备都提到了真空离心10年设备和过程均提到了引流罩和因留空后者未提到引流冒也未提到引流孔的形状7、在支持的基础上合理概括上位08年油炸食品vs马铃薯并列07年带状或绳状数值范围功能限定：用于撕开的部件多个实施例时特征归纳（原文不容易照抄）07年3个实施例答案可以有几种8、不要纠结于附图标记从权主题名称可不写定语引用关系简化不影响得分独权不划界不影响得分无效中不要重新划界9、2个以上独权单一性交底书中分别独立详述了不同的主题，且有单一性从材料中照抄出来即可10年真题交底书中一个主题的描述中采用了引用形式涉及到另一个主题直接从材料原文中改写07年包装体包装体长带10、简化原则保证把概念体现出来的前提下，重点放在不同意的部分，认同的不提新颖性有新颖性：权1与D1相比，区别特征在于xxx，两者技术方案不同，因此权1有新颖性完美写的话可以仅简单写D1公开了……主题无新颖性：权1与D1相比，…………（特征一一对比），技术方案相同，技术领域，技术问题，技术效果相同，因此权1无新颖性创造性只有一个对比文件时权1相对于D1区别特征为xxxx 解决……技术问题D1没有给出启示，也不属于公知常识，对于本领域技术人员非显而易见，具有突出的实质性特点，该区别技术特征带来……效果，具有显著进步有2个对比文件或一个对比文件的2个实施例区别特征未被公开区别特征被公开，但作用不同甚至相反其他（具体看材料提示）11、出现问题总结单一性不是无效条款抵触申请不能评价创造性技术领域不同优先权证据补充代理人资格核查无效补充证据12、答题技巧新创评判时最好列时间轴技术特征对照表可帮助找到最接近现有技术和区别技术特征答复审意和无效时是否按意见顺序逐条答复？不需要，最好按缺陷类型答复可大致分新，创，清楚，支持……也不一定按照权利要求的顺序弄清题意和题目指定的材料的使用范围理解题意，通读题目，避免重复作答10年简述合案理由；；说明权利要求相对于现有技术具有新创的理由Sailing qq429135041、字迹工整即可一个老师3天看500个卷子，标准语段一定要写不要把答题卡填错位置2、划界不影响分数3、名称食品料理机可有偏差豆浆机食物榨汁机4、特征4 1 0 -5不当概括扣分非必要技术特征写入独权扣分缺必要技术特征扣分从权：分数有上限不会多写多给分7个左右吧不重复给分不重叠该写在独权的特征写在从权了，不会给分可拆分引用关系所有从权都引权1会扣分有一定变化有递进的引用即可不必写多项从权，单项引用即可方法单独一段，提示大家要写方法独权答案中适当概括了方法的过程，如果照抄原文也可以不扣分5、合案理由分案：该分的分，不该分的不分给分该分的不分不该分的分了都不得分分案不要求写从权，从权不得分单一性年年考10年真题分案中有2个独权也要写合案理由6、忠实原文上位概括要慎重如果原文有问题，要适当更改和回避：例如交底书中控制方式写权利要求记得改成控制方法原文中的大实话用于加热的加热器有人照抄，虽然阅卷时未扣分，当然最好自己总结一下避免这些附图标记不写附图标记可能只扣一点点分所述不所述：所述可以写但要少用用的时候注意有无引用基础7、新颖性单独对比区别技术特征结论创造性区别，问题（相适应）启示，理由（不能不说理）公知，结论（有人遗漏非公知）从权简单写一句话即可送分的，千万别漏注意发明和实用新型区别可以写D1 D2 但要事先告诉：附件2简称D1 附件3简称D28、最后留得撰写题20分分值少得话，权利要求不多，2-3个优先权概念时间相同主题在后申请pct进中国，在先申请不视撤留待后续无效解决。
竞争情报对提升企业竞争保障的战略研究
杨德平;陈中文;滕胜娟
【期刊名称】《武汉纺织大学学报》
【年(卷),期】2006(019)008
【摘要】在激烈的市场竞争中,竞争情报越来越多地受到企业的重视,提高企业的情报竞争力也成为现代企业生存和发展的基本战略,也是提高企业核心竞争力的重要
组成部分.本文较详尽地论述了企业监视竞争环境、分析竞争对手、制定竞争战略、保护信息安全和快速反应等五个方面的情报竞争力的培养、提高与发展问题.
【总页数】3页(P52-54)
【作者】杨德平;陈中文;滕胜娟
【作者单位】黄冈师范学院,图书馆,湖北,黄冈,438000;黄冈师范学院,图书馆,湖北,
黄冈,438000;武汉科技学院,图书馆,湖北,武汉,430073
【正文语种】中文
【中图分类】G350
【相关文献】
1.动态环境下企业竞争情报战略研究 [J], 刘冰
2.全球化背景下的企业竞争情报战略研究 [J], 李建华
3.基于知识资本的中小企业竞争情报战略研究 [J], 徐津铭
4.企业竞争情报战略研究 [J], 樊涛
5.图书馆开展企业竞争情报业务的思考——浅述企业竞争情报专职业务机构的模型以及发展可能性 [J], 黄恒毅
因版权原因，仅展示原文概要，查看原文内容请购买。
武汉思博培训俱乐部会刊２００６年４月２４日 总第①期 每月最后一个星期一出刊创刊号２００６年４月①武汉思博培训俱乐部关于思博加入我们，促进交流和分享QQ 群号：22060293苍蝇杀死了他 哲理故事培训结束后要做什么工作？ 新员工培训必不可少的内容培训之道如何甄选和管理培训供应商专题策划目 录e-mail：nikohr@本期主编： niko 执行主编：niko俱乐部QQ 群：22060293 武汉思博培训俱乐部创刊词培训前沿美国企业员工培训的发展趋势介绍编者按：摘自培训者俱乐部文章，来源北电加油站。
美国企业员工培训一直可世界员工培训方面的典范，其在近二、三十年内，员工的培训工作得到了迅猛的发展，大致体现在以下七个方面：一、培训内容：从狭隘单一的职业培训转向丰多彩的全方位培训在传统的培训工作中，培训方式一般是在职培训和脱产培训，这主要是针对一项具体的工作中所需的技能和知识而进行的培训，如生产线上的工人的技术培训工作。
而在现在乃至未来的培训中，不仅要求员工掌握其工作中所需的知识和技能，同时还要求员工掌握沟通技巧、团队工作技巧等诸多方面的技巧。
因为未来的社会是协作性社会，以合作求竞争才能达到利的最大化。
在这种情况下，只有掌握多种技能的员工才能在现代企业的工作中如鱼得水，在日益激烈的竞争中取胜。
1999年摩托罗拉大学的培训课程科目是一本厚厚的近300页的十六开的大书。
内容涉及与本企业有关的方方面面。
美国戴尔公司的培训内容则包括企业文化定位、术技能、领导艺术及挖掘员工潜能方面的课程。
而ibm 公司基层经理在走上新岗位的第一年要接受80小时的课堂培训，内容包括公司的历史信念、政策、习惯做法以及如何对员工进行激励、赞扬、劝告等基本管理技能；部门经理则还要接受有效沟通、人员管理、经营思想、战略计划等方面的培训。
二、培训态度：企业从漠然视之到高度重视在近二十年的发展中，美国企业越来越重视员工的培训工作。
有数据表明，1983年用于正式培训的支出是396.66亿美元，而在1991年已达到了633.33亿美元，年增幅达到59.26%。
在美国，公司一般拿出其销售收入的1—5%或工资总额的8—10%用于培训工作。
如：美国通用电器公司每年用于员工培训和领导发展的费用高达10亿美元。
一些企业还把培训作为福利奖励给表现良好的员工，即公司根据个人发展的计划安排其所需参加的培训内容，以帮助员工更好地实现自身的职业生涯发展。
与此同时，美国企业也通过提供培训课程、在岗培训、报销学费、资助参加管理研讨会等多种形式来支持员工参加培训工作。
这也说明企业在物质上、精神上都支持员工参加培训。
同时，各个企业的培训机构作为服务部门，也成为企业中不可缺少的至关重要的一个人部门。
人力资源部员工工资在企业中也普遍高于其他部门。
从这几个方面，我们可以看出企业对培训工作越来越重视。
三、培训方法：从单一化、传统化到科学化、多样化在传统的培训中，多是“师傅带徒弟”式的言传身教方法，即以课堂讲授和实地观摩为主。
课堂讲授多是“填鸭式”，教师在上面滔滔不绝，学员则在下面昏昏欲睡。
在实地观摩中，多是培训师带领学员到生产一线观看工人的实际操作。
培训方法单调枯燥，员工被动地参与其中，常常感到苦不堪言，因此员工的抵触情绪较高。
而现代的培训方法则是多种多样的，既有讲授，又有游戏、角色扮演小组讨论等方法。
在一门培训课程中，员工都要主动出击，带着问题参加学习。
在学习过程中培训师还会穿插使用各种培训方法：小组讨论法可使学员之间相互交流，沟通；游戏法可使学员在“玩耍”中领悟培训内容的含义；角色扮演法则使学员设身处理地从顾客角度着眼，体会顾客的感受。
培训师让每一位学员都主动地参与其中，畅所欲言，给每一位学员一个自我表现的机会。
多种多样的培训方法使培训内容丰富多彩，即加深了员工对培训内容的理解和掌握，又更大地发挥了员工的积极性和主动性。
这种参与式培训方法较以往的被动式的培训方法更为科学、更为有效，大大地提高了培训质量。
四、培训工具：从简单的低科技含量到复杂的高科技含量在传统的以讲授为主的培训中，培训工具十分简单，一间教室、一张黑板、一本教材。
这种培训往往易受时间、地点、人员方面的限制，难以收到良好的培训效果。
而现代的培训工具则最大程度地把高科技产品应用于培训工作中，如：录像机、投影机、计算机。
现代的互联网上的远程教育还可以把世界各地的员工招集在一起，打破了时空的限制，节省了员工的异地培训的差旅费用、时间，大大地减低了培训成本。
近年来发展的机上培训，员工不用再到生产线上进行实地操作，只需把培训软件装入计算机内，即可在计算机上进行模拟操作，出现错误后，也可以机上修改，降低了错误成本，方便了培训工作，又使培训工作上了一个新台阶。
例如：美国戴尔计算机公司已使员工在网上获得更多的正规培训，在戴尔公司的某一新产品投放市场之前，员工就可以从网上获得关于该产品的图文并茂的详细说明，从中可以了解如何安装使用新产品。
相对而言，网上培训已充分显示其快捷性和实用性，教室培训已处于次要地位。
五、员工态度：从消极对抗到积极参与传统观念中，参加培训的员工都是那些工作表现不佳的人员，再加上培训内容枯燥，方法单调，工具落后，员工对参加培训有抵触情绪，即使参加了培训也是混日子。
而21世纪是知识经济时代，而知识经济最大的特点就是日新月异的知识更新。
在这种情况下，工作种类也随知识的更新而更新，传统的工作岗位在不断地减少，甚至是消失，而更多的新型的工作岗位又为断地涌现出来。
企业员工为了避免被淘汰，只有积极提高更新知识和技能以适应社会的发展。
在这种社会大背景下，员工的学习积极性和主动性大大提高。
同时，在员工培训中，员工可以向经理人员提出自己需要接受的培训课程，公司培训部门、经理人员、员工三方协商安排。
这种培训因为有员工本人的参与和决策，而且是员工的实际所需，员工往往更有主动性，更乐于参与，培训效果也会更好。
六、培训对象：20世纪50年代，美国全体就业人员中，职业工作者占20%，包括教师、医生、管理人员；技术人员占20%，包括工程师、技术人员；而非技术人员占到60%，主要由体力劳动者构成。
而伴随着高等教育的普及，在1997年职业工作者的比例仍是20%，但技术人员占60%，非技术人员占20%，非技术人员的减少导致管理人员的工作任务的变动，要求加强对管理人员的培训工作。
美国制造研究会的一项研究也表明：在一次调查中，管理人员占总调查对象的12.8%，但其参加企业提供的正式培训的人次数则占总培训人次的19%。
这在一定程度上说明管理人员的培训人次数已经超过非技术人员。
企业上把其培训对象的重点转向管理人员。
同时，美国也是世界上最早开展企业管理人员在培训的国家。
企业、高校和政府三位一体不断扩大在职培训人员的数量和范围，全美600多所工商管理学校中，有2/3的举办各种形式的在职管理人员培训进修班。
美国通用电器公司的总裁杰克·韦尔许就十分重视对管理人员的培训，每年都定期到总部的培训中心给经理人员授课，在其任总裁的18年中，共250次向15000名经理人员授课。
七、培训模式：从单一化到立体化、专业化美国大企业现在一般都设有自己的专业培训机构，常见的形式有培训中心、人力资源开发中心、公司大学等等。
超大型公司的培训机构多以公司大学的形式出现，如：摩托罗拉大学，这些大学都有自己的独立的教学培训设施，员工可以在大学里接受培训，食宿都可在大学里，十分方便。
同时，公司也可以委托学校代培或企业与学校联合培训，企业与企业进行联合培训。
据统计，美国企业培训中68的在企业内部进行，38%的则由社会各类学校和培训机构承担。
而小型公司则趋于把培训工作外包给专职的培训公司或管理顾问机构，即在培训方面进行虚拟管理。
公司把培训职能进行外包部分原因是因为这些机构不仅有足够的师资队伍、充分的信息、专业的培训技巧，而且还可以提供更广泛的交流机会。
小型公司把培训工作外包出之去既可以保证培训的质量，同时因为本企业不再设专职的培训师，也可以减轻本企业培训工作方面的负担，降低成本。
近年来，一些大型公司也青睐了“外包”这种形式。
“外包”正成为现代员工培训的一种流行趋势。
（友情提醒：人力资源外包将作为俱乐部某一期专题策划内容详谈，敬请关注。
）专题策划 如何甄选和管理培训供应商（原创）前言：企业对员工培训越来越重视，逐步加大了对培训的投资，人力资源部门在培训资源的获取和选择方面有了更多的余地，但是在面对市场上鱼龙混杂的培训机构和顾问公司，怎样才能选择适合自己的外部培训公司进行合作，从而更好得推进和实现公司一系列的培训计划和目标呢？本期专题策划将和大家共同来探讨这个问题。
一、企业培训内外部资源比较企业逐渐认识到人才培养对于组织长远发展的意义，加大了对培训的投入。
在实现培训计划的方法上，主要采用两个方式：一是内部讲师和资源，二是外部专业培训机构，而从操作性和专业方面，外部培训机构始终扮演了其中最主要的角色，企业内部讲师因为推行涉及的问题较多、周期较长、培训效果不确定性大等诸多原因，很多企业选择了与外部培训机构合作。
企业与外部专业培训机构合作，主要有两类的企业。
一类是处在培训工作初期的企业，他们希望培训公司能提供特定的单项课程，解决现有最紧迫的问题，第二类企业是培训体系相对比较成熟的企业，他们把重点放在培训需求分析、培训效果评估和转化上来，而把培训实施的工作外包给培训公司，通常以系列课程、课程包、学习卡等形式实现。
国内培训市场经过数十年的开拓和完善，虽然整个市场鱼龙混杂，相对比较混乱，但也是涌现出一批有实力、专业的培训公司，他们在为企业提供全面的教育训练解决方案积累了一定的经验和优势，主要体现在对资源（讲师、课程等）的集中掌握、培训专业程度、成本效益、对培训需求和实施快速反应等方面，所以，无论企业处在什么阶段，对培训的需求程度如何，都离不开与培训供应商的互动和合作。
二、获得外部培训供应商的渠道似乎这个话题不应该当着本期专题的一个问题点来提出，但实际上，很多企业正在为找不到合适的培训供应商和课程而发愁，除开甄选的原因，大部分就是因为培训管理者手中没有全面、有针对性的培训供应商资料，那么，如何获得培训供应商的资料呢？笔者总结以下几点，也希望网友、同仁提出其他意见。
1、公司收到的培训供应商资料。
培训公司的营销力量使得他们能想法设法得到公司人力部的联系方式，然后进行电话、电子邮件等联系，将资料发给公司，这个渠道是最常见也是量最大的一个。
2、朋友、同行介绍。
通过与同行的交流获得培训供应商的资料。
3、网络寻找。
自己通过网络寻找课程和相应培训公司，充分运用网络信息量大、更新快的特点，而且，得到的课程更有针对性，现在也有很多机构提供了培训课程和培训公司黄页的服务，更方便寻找，如中华培训网、中人网黄页等。
