9451GUIDELINES FOR LINING OF CANALS IN EXPANSIVE SOILS

·耳鸣专辑·解读美国《耳鸣临床应用指南》贺璐王国鹏龚树生首都医科大学附属北京友谊医院耳鼻咽喉头颈外科（北京100050）【摘要】2014年10月美国《Otolaryngology－Head and Neck Surgery》杂志增刊发表了《耳鸣临床应用指南（Clinical Practice Guideline:Tinnitus）》。

该《指南》由David E.Tunkel等23位学者共同制定，是首部用于评估和治疗慢性耳鸣的指南，旨在为从事耳鸣研究与治疗的专业人员提供基于循证医学证据的建议。

《指南》涉及的患者群体是患有持续失代偿性的原发性耳鸣患者（18岁及以上）。

本文试结合我国目前耳鸣诊治现状将该《指南》作一解读。

【关键词】耳鸣（tinnitus）；循证医学（Evidence-Based Medicine）；指南[文献类型]（Guidebooks[Publica⁃tion Type]【中图分类号】R764【文献标识码】A【文章编号】1672-2922（2016）02-149-4Interpretation of the AAO-HSN Clinical Practice Guideline:TinnitusHe Lu,WANG Guopeng,GONG ShushengDepartment of Otolaryngology Head and Neck Surgery,Beijing Friendship Hospital,Capital University of MedicalSciences,(Beijing100050)Corresponding author:GONG Shusheng Email:gongss@【Abstract】Clinical Practice Guideline:Tinnitus was published as a supplement to the Otolaryngology－Head and Neck Surgery in October2014.It is the first guideline for tinnitus evaluation and treatment,composed by23authors.The purpose of this guideline is to provide evidence-based recommendations for clinicians managing patients with tinnitus.The target patient population is limited to adults(18years and older)with primary tinnitus that is persistent and bothersome.This article aims at giving an interpretation of the guideline in connection with the development of tinnitus management in China.【Key word】tinnitus;Evidence-Based Medicine;Guidebooks[Publication Type]Foundation：Project in the National Science and Technology Pillar Program during the twelfth Five-year Plan Period(2012BA112B05) Declaration of interest:The authors report no conflicts of interest.美国《耳鸣临床应用指南（Clinical Practice Guideline:Tinnitus）》［1］（以下简称美国指南）由耳鸣指南制定小组David E.Tunkel等23位学者共同制定,2014年10月于《Otolaryngology－Head and Neck Surgery》增刊发表。

(2024年详解)国家慢性疾病编码指南英文版(2024 Explained) National Chronic Disease Coding GuidelinesIn 2024, the National Chronic Disease Coding Guidelines were introduced to provide a standardized system for classifying and coding chronic diseases. These guidelines aim to streamline the process of recording and categorizing chronic health conditions, making it easierfor healthcare providers to track and manage patient information effectively.Chronic diseases, such as diabetes, heart disease, and cancer, are long-lasting conditions that require ongoing medical attention. By following the National Chronic Disease Coding Guidelines, healthcare professionals can accurately document these conditions in medical records, ensuring that patients receive the appropriate care and treatment.The coding guidelines include a comprehensive list of codes for different chronic diseases, each corresponding to a specific diagnosis. These codes help healthcare providers accurately identify and classify a patient's condition, enabling them to provide tailored treatment plans and monitor the progression of the disease over time.In addition to standardizing the coding process, the National Chronic Disease Coding Guidelines also promote consistency and accuracy in healthcare documentation. By using the prescribed codes, healthcare providers can communicate effectively with other professionals, insurance companies, and government agencies, ensuring that all relevant parties have access to the necessary information.Overall, the National Chronic Disease Coding Guidelines play a crucial role in improving the quality of care for patients with chronic conditions. By adhering to these guidelines, healthcare providers can better manage and monitor chronic diseases, ultimately leading to better health outcomes for individuals with long-term health issues.。

2024年度慢阻肺最新指南详解英文版2024 Annual Update on COPD GuidelinesWelcome to the comprehensive guide on the latest recommendations for managing Chronic Obstructive Pulmonary Disease (COPD) in 2024. This document will provide an in-depth analysis of the most recent guidelines to help healthcare professionals and patients navigate the complexities of COPD management effectively.Understanding COPDCOPD is a chronic respiratory condition characterized by airflow limitation that is not fully reversible. It encompasses conditions such as emphysema and chronic bronchitis, leading to symptoms like coughing, wheezing, and shortness of breath. Managing COPD requires a multidisciplinary approach to improve quality of life and reduce exacerbations.Key Updates in 2024 GuidelinesThe 2024 guidelines emphasize early diagnosis through spirometry testing and personalized treatment plans based on the severity of the disease. Smoking cessation remains a critical component of COPD management, along with vaccination against respiratory infections to prevent exacerbations. Pulmonary rehabilitation and exercise training are recommended to improve exercise tolerance and quality of life for COPD patients.Pharmacological InterventionsThe guidelines highlight the importance of pharmacological interventions, including bronchodilators and inhaled corticosteroids, to reduce symptoms and exacerbations in COPD patients. Long-acting bronchodilators such as LABAs and LAMAs are recommended as first-line therapy, with the addition of ICS for patients with frequent exacerbations. Newer therapies, such as PDE4 inhibitors and biologics, are also discussed as options for severe COPD cases.Non-Pharmacological ApproachesIn addition to medication, non-pharmacological approaches such as oxygen therapy, pulmonary rehabilitation, and nutritional support play a crucial role in managing COPD. Patient education on self-management techniques and coping strategies is essential for long-term success in controlling the disease. Surgical interventions like lung volume reduction or lung transplantation may be considered for select cases of severe COPD.ConclusionThe 2024 guidelines provide a comprehensive framework for managing COPD, focusing on early diagnosis, personalized treatment plans, and a holistic approach to care. By following the recommendations outlined in this document, healthcare professionals can improve outcomes for COPD patients and enhance their quality of life. Stay informed, stay proactive, and together, we can make a difference in the lives of those living with COPD.。

Guidelines for Resident Training in Critical Care MedicineCopyright © by the SOCIETY OF CRITICAL CARE MEDICINEThese guidelines can also be found in the November 1995 issue of Critical Care Medicine --Crit Care Med 1995 Nov; 23(11):1920-1923Society of Critical Care Medicine701 Lee StreetSuite 200Des Plaines, IL 60016Phone: 847/827-6869Society of Critical Care MedicineGuidelines for Resident Trainingin Critical Care MedicineGuidelines/Practice Parameters CommitteeAmerican College of Critical Care Medicinethe ofSociety of Critical Care MedicineThe Society of Critical Care Medicine has become increasingly concerned that residency training programs be consistent with regard to the management of critical illness. Variations in training may be related to the explosion of knowledge and technology in critical care, and to the fact that most training programs limit the resident physician's intensive care unit experience to managing patients within that program's specialty. Training and management of patients with critical illness may become more fragmented as a result of current emphasis on primary care and de-emphasis on specialty training.This document intends to define cognitive and procedural skills that residents should possess on completion of graduate training in order to be able to formulate and initiate a treatment plan for the critically ill patient.To accomplish this goal, the American College of Critical Care Medicine formed a multidisciplinary task force to review current requirements for residency programs in Internal Medicine, Surgery, Anesthesiology, Pediatrics, and Emergency Medicine (1). The task force utilized recognized principles (2) to promulgate a consensus core curriculum of cognitive knowledge and procedural skills that the American College of Critical Care Medicine and the Society of Critical Care Medicine believe to be necessary for physicians to effectively approach the complex problems encountered in the critically ill patient.Each of the following recommendations has been assigned a Level 3 "rating" that reflects the weight of scientific evidence, expert opinion, and clinical practice experience which the recommendation is based, according to the following scale:Level 1. Convincingly justifiable on scientific evidence alone;Level 2. Reasonably justifiable by available scientific evidence and strongly supported by expert critical care opinion;Level 3. Adequate scientific evidence is lacking but widely supported by available data and expert critical care opinion.RECOMMENDATION 1Upon completion of residency training, the physician should have achieved proficiency in the recognition and initial management of problems commonly encountered in the intensive care unit.This proficiency includes, but is not limited to, sepsis, acute respiratory failure, acute renal failure,hemodynamic instability, overdoses and poisonings, acute neurologic insults, acute electrolyte andendocrine emergencies, and coagulation disorders. For less common problems, the trainees gain aknowledge base that allows them to formulate a differential diagnosis, initiate a management plan,and request appropriate consultations.RECOMMENDATION 2Methods of teaching critical care should be left to the discretion of individual program directors.Approaches to resident teaching depend greatly on available facilities, patient population base, andfaculty. It is likely that the majority of cognitive skills will be conveyed through didactic lectures andpatient care rounds. Procedural skills must be taught both in didactic sessions and in demonstrationsat the bedside. Distribution of pertinent medical literature and a curriculum summary is encouraged.RECOMMENDATION 3The following core curriculum is recommended.These curriculum guidelines are not intended to constrain training programs nor to mandateinstruction in all topics included. Rather, they should serve as a goal toward which training programsshould strive.CredentialsI. SpecificA. All housestaff should achieve Advanced Cardiac Life Support (ACLS), Pediatric Advanced LifeSupport (PALS), Advanced Trauma Life Support (ATLS) provider status, as appropriate, andmaintain this throughout their training.SkillsII. CognitiveA. Cardiovascular1. Recognition and Acute Management offorms)a. Shock(allarrhythmiasb. Cardiacc. Cardiogenic pulmonary edemacardiomyopathiesd. Acuteemergenciese. Hypertensiveof2. Principlestherapyinotropicanda. Vasoactiveb. Arterial, central venous, and pulmonary artery catheterization and monitoringc. Cardiovascular physiology in the critically ill patientB. Respiratory1. Recognition and Acute Management ofa. Acute and chronic respiratory failureb. Statusasthmaticusc. Smoke inhalation and airway burnsd. Upper airway obstruction, including foreign bodies and infectiondrowninge. Nearf. Adult respiratory distress syndrome (noncardiogenic/capillary leak pulmonaryedema)of2. Usea. Pulmonary function tests including bedside spirometryb. Arterial blood gas analysis3. Principles and Application oftherapya. Oxygenb. Mechanical ventilation (invasive and noninvasive) including indications, modes,complications, and weaningC. Renal1. Recognition and Acute Management ofdisturbanceselectrolytea. Fluidandfailureb. Renaldisordersc. Acid-baseof:2. Principlesa. Drug dosing in renal failureb. Fluid and electrolyte therapy in the critically ill patientc. DialysisD. Central Nervous System (CNS)1. Recognition and Acute Management ofa. Comaoverdoseb. Drughydrocephalusc. Acuted. Brain death evaluationstatee. Persistentvegetativeaccidentsvascularf. Intracranialepilepticusg. Statusinfectionh. Intracranialhypertensioni. Intracranialinjuryj. SpinalcordE. Metabolic and Endocrine1. Recognition and Acute Management ofcrisisa. Hypoadrenalinsipidusb. Diabetesketoacidosisc. DiabeticofAlimentation2. Principlesa. Enteralb. ParenteralDiseaseF. Infectious1. Recognition and Acute Management ofa. Sepsisincludinginfections,Acquiredandopportunisticb. Hospital-acquiredImmunodeficiency Syndromeof2. Principlesa. Antibiotic selections and dosage schedules for the critically ill patientb. Infection risks to healthcare workersG. HematologicDisorders1. Recognition and Acute Management ofinhemostasisa. Defectsdisordersb. Hemolyticc. Hematologic dysplasias and their complicationscrisiscelld. Sickledisorderse. Thromboticof2. Principlesfibrinolytictherapyanda. Anticoagulationcomponenttherapyb. Bloodc. Plasmapheresis for acute disorders including neurologic and hematologic diseasesDisordersH. Gastrointestinal1. Recognition and Acute Management ofbleedinga. Gastrointestinalfailureb. Hepaticviscusc. Perforationof2. Principles of prophylaxis against stress ulcer bleedingI. Principles of Transplantation1. Immunosuppression2. Infections in the immunocompromised patientrejection3. Organdonation4. OrganJ. Principles of Sedation, Analgesia, and Neuromuscular Blockade in the Critically Ill PatientK. Monitoring & Biostatistics1. Prognostic indices such as Acute Physiology and Chronic health Evaluation (APACHE),Therapeutic Intervention Scoring System (TISS), and Pediatric Risk of Mortality (PRISM)as indicated2. Respiratory monitoring (pulse oximetry, transcutaneous P O2, P CO2, and end-tidal CO2)calorimetry3. IndirectL. Ethical and Legal Aspects of Critical Careorders1. Do-not-resuscitate2. Principles of informed consentpatients3. Rightsof4. Withholding and withdrawing life support5. Advance directives (Patient Self-Determination Amendment of 1991)IssuesM.Psychosocial1. Understanding the effect of life-threatening illness on patients and their families2. DeathdyingandN. Transport of the Critically Ill Patient1. Stabilizationmonitoring2. EquipmentandO. Principles of Resuscitation and Postoperative Management of the Patient With Acute Injury III. Supplemental Cognitive SkillsIn addition to the core curriculum for all residents, the following list represents entities thatare unique to either the adult or pediatric population.A. Adult Critical Care Training1. Recognition and Acute Management ofinfarctiona. Myocardialdissectionb. Aorticcomac. Hyperosmolard. Pheochromocytomae. Critical illness in the pregnant patientf. Thyroid storm and myxedema comag. Pancreatitisinfarctionh. Mesenterici. Pulmonaryembolismtamponadej. Cardiacinsufficiencyvalvulark. Acute2. Living wills, advance directives, durable powers of attorneyTrainingB. Pediatric1. Recognition and Acute Management ofa. Common forms of congenital heart disease (cyanotic and acyanotic)b. Bronchiolitismetabolismc. Inbornoferrors2. Perioperative management of the critically ill child3. Evaluation and acute management of the critically ill neonate4. LegalIssuesa. Child abuse and neglect statuteslegislationb. BabyDoeIV. Core Procedural Skills for ResidentsIn addition to practical training in the following procedural skills, the resident must have anunderstanding of the indications, contraindications, complications, and pitfalls of theseinterventions. Due to the variability of individual training programs, practical experiencemay be limited for some procedures.ManagementA. Airway1. Maintenance of an open airway in the nonintubated patient2. Ventilation by bag-mask systemsintubation3. Trachealpneumothorax4. ManagementofB. Circulation1. Arterial puncture and cannulation2. Insertion of central venous catheters3. Pericardiocentesis in acute tamponadeinterpretation4. Dynamicelectrocardiogram5. Cardioversioncatheterizationartery6. Pulmonarypacing7. TranscutaneousREFERENCES 1. American Medical Association/Accreditation Council for Graduate Medical Education: Essentials andInformation Items, 1993-19942. American Medical Association/Specialty Society Practice Parameters Partnership: Attributes to Guide theDevelopment of Practice Parameters. Chicago, American Medical Association, 1990These guidelines have been developed by the Guidelines Committee of the Society of Critical Care Medicine (SCCM), and thereafter reviewed and revised by the Society's Council. These guidelines reflect the official opinion of the Society of Critical Care Medicine and do not necessarily reflect, and should not be construed to reflect, the view of certification bodies, regulatory agencies or other medical review organizations.* Writing Panel: Antoinette Spevetz, MD, Richard J. Brilli, MD (principal authors); Jonathan Warren, MD, FCCM (committee chair); Robert W. Bayly, MD, FCCM; Linda Carl, RN, BSN; Jay Cowen, MD; Michael N. Diringer, MD; Andrew B. Egol, DO, FCCM; Charles J. Fisher Jr., MD, FCCM; Dennis M. Greenbaum, MD, FCCM; Marilyn T. Haupt, MD, FCCM; Judith Jacobi, PharmD, FCCM; Diana L. Nikas, RN, MN, FCCM; Roland M. H. Schein, MD, FCCM; James R. Stone, MD, FCCM; Suzanne K. Wedel, MD, FCCM; Jack E. Zimmerman, MD, FCCM.Approved by SCCM Council 5/95. To be revised in 2000.。

2024中国心脏病防治指南英文版2024 Chinese Heart Disease Prevention and Treatment GuidelinesIn 2024, China continues to prioritize the prevention and treatment of heart disease. The guidelines aim to provide comprehensive strategies for reducing the incidence and impact of heart-related conditions.Importance of PreventionPrevention remains a key focus in the fight against heart disease. Emphasizing healthy lifestyle choices, such as regular exercise, balanced diet, and stress management, can significantly reduce the risk of developing heart problems.Early Detection and DiagnosisEarly detection plays a crucial role in effectively managing heart disease. Regular health check-ups and screenings are recommended to identify potential issues before they escalate.Treatment ApproachesTreatment for heart disease may vary depending on the individual's condition. From medication to surgical interventions, the guidelines outline a range of options to address different aspects of heart-related ailments.Lifestyle ModificationsEncouraging lifestyle modifications, such as quitting smoking, reducing alcohol consumption, and managing weight, can greatly improve heart health and overall well-being.Importance of EducationEducating the public about the risks and warning signs of heart disease is essential for early intervention and prevention. Awareness campaigns and community outreach programs can help spread crucial information to a wider audience.Collaborative EffortsCollaboration between healthcare professionals, researchers, policymakers, and the public is vital in implementing effective strategies for heart disease prevention and treatment. Working together can lead to better outcomes and improved quality of life for individuals affected by heart conditions.ConclusionThe 2024 Chinese Heart Disease Prevention and Treatment Guidelines serve as a roadmap for promoting heart health and reducing the burden of heart disease in China. By following these guidelines and adopting healthy habits, individuals can take proactive steps towards safeguarding their heart health for years to come.。

ins指南对静脉治疗的目标要求英文回答：The goal of intravenous therapy, as outlined in the INS guidelines, is to provide safe and effective treatment through the administration of medications, fluids, and blood products directly into the veins. This form of therapy allows for rapid absorption and immediate systemic effects, making it a crucial method for delivering critical care and maintaining patient well-being.One of the primary objectives of intravenous therapy is to ensure the correct dosage and concentration of medications or fluids are administered to the patient. This requires careful calculation and accurate preparation of the IV solution, considering factors such as the patient's weight, age, and medical condition. By adhering to the recommended guidelines, healthcare professionals can minimize the risk of medication errors and potential harm to the patient.Another important goal of intravenous therapy is to maintain the patency and integrity of the intravenous access device. This involves regular assessment of the insertion site, monitoring for signs of infection or infiltration, and ensuring proper flushing and flushing technique. By preventing complications such as catheter-related bloodstream infections or occlusions, healthcare providers can optimize the delivery of therapy and reduce the need for device replacement or reinsertion.Furthermore, the INS guidelines emphasize the importance of patient education and involvement in their own care. Patients should be informed about the purpose and potential side effects of the medications or fluids being administered intravenously. They should also be educated on how to recognize and report any complications or adverse reactions. By empowering patients to actively participate in their treatment, healthcare professionals can enhance patient satisfaction and improve overall outcomes.In addition to these objectives, the INS guidelinesalso highlight the importance of maintaining aseptic technique during the preparation and administration of intravenous therapy. This includes proper hand hygiene, use of personal protective equipment, and adherence to sterile practices. By following these guidelines, healthcare providers can minimize the risk of infection and ensure the safety of both the patient and the healthcare team.Overall, the goal of intravenous therapy, as outlinedin the INS guidelines, is to provide safe, effective, and patient-centered care. By adhering to these guidelines, healthcare professionals can optimize the delivery of therapy, minimize complications, and promote positive outcomes for their patients.中文回答：静脉治疗的目标要求是根据INS指南，通过将药物、液体和血液制品直接注入静脉，提供安全有效的治疗。

Guideline for Industry The Need for Long-term Rodent Carcinogenicity Studies of PharmaceuticalsMarch 1996ICH S1ATable of ContentsRMATION (1) (1)II.HISTORICAL BACKGROUND (2) (1)III.OBJECTIVE OF THE GUIDELINE (3) (2)IV.FACTORS TO CONSIDER FOR CARCINOGENICITY TESTING (4) (2)A.Duration and Exposure (4.1) (2)B.Cause for Concern (4.2) (3)C.Genotoxicity (4.3) (3)D.Indication and Patient Population (4.4) (3)E.Route of Exposure (4.5) (4)F.Extent of Systemic Exposure (4.6) (4)G.Endogenous Peptides and Protein Substances or Their Analogs (4.7) (5)V.NEED FOR ADDITIONAL TESTING (5) (5)iThis guideline was developed within the Expert Working Group (Safety) of the International Conference on 1Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) and has been subject to consultation by the regulatory parties, in accordance with the ICH process. This document has been endorsed by the ICH Steering Committee at Step 4 of the ICH process, November 29, 1995. At Step 4 of the process, the final draft is recommended for adoption to the regulatory bodies of the European Union, Japan and the USA. This guideline was published in the Federal Register on March 1, 1996 (61 FR 8153) and is applicable to drug and biological products. Although this guideline does not create or confer any rights for or on any person and does not operate to bind FDA or the industry, it does represent the Agency’s current thinking on long-term rodent carcinogenicity studies of pharmaceuticals. For additional copies of this guideline, contact the Drug Information Branch, HFD-210, CDER, FDA,5600 Fishers Lane, Rockville, MD 20857 (Phone: 301-827-4573) or the Manufacturers Assistance and Communication Staff (HFM-42), CBER, FDA, 1401 Rockville Pike, Rockville, MD 20852-1448. Send one self-addressed adhesive label to assist the offices in processing your request. An electronic version of this guidance is also available via Internet using the World Wide Web (WWW) (connect to the CDER Home Page at /CDER and go to the “Regulatory Guidance” section).GUIDELINE FOR INDUSTRY 1THE NEED FOR LONG-TERMRODENT CARCINOGENICITY STUDIES OFPHARMACEUTICALSRMATION (1)The objectives of carcinogenicity studies are to identify a tumorigenic potential in animals and to assess the relevant risk in humans. Any cause for concern derived from laboratory investigations,animal toxicology studies, and data in humans may lead to a need for carcinogenicity studies. The practice of requiring carcinogenicity studies in rodents was instituted for pharmaceuticals that were expected to be administered regularly over a substantial part of a patient's lifetime. The design and interpretation of the results from these studies preceded much of the available current technology to test for genotoxic potential and the more recent advances in technologies to assess systemic exposure. These studies also preceded our current understanding of tumorigenesis with nongenotoxic agents. Results from genotoxicity studies, toxicokinetics, and mechanistic studies can now be routinely applied in preclinical safety assessment. These additional data are important not only in considering whether to perform carcinogenicity studies but for interpreting study outcomes with respect to relevance for human safety. Since carcinogenicity studies are time consuming and resource intensive, they should be performed only when human exposure warrants the need for information from life-time studies in animals in order to assess carcinogenic potential.II.HISTORICAL BACKGROUND (2)In Japan, according to the 1990 “Guidelines for Toxicity Studies of Drugs Manual,”carcinogenicity studies were needed if the clinical use was expected to be continuously for 6months or longer. If there was cause for concern, pharmaceuticals generally used continuously for less than 6 months may have needed carcinogenicity studies. In the United States, mostIt is expected that most pharmaceuticals indicated for 3-months treatment would also likely be used for 62months. In an inquiry to a number of pharmaceutical research and regulatory groups, no cases were identified in which a pharmaceutical would be used only for 3 months.2pharmaceuticals were tested in animals for their carcinogenic potential before widespread use in humans. According to the U.S. Food and Drug Administration, pharmaceuticals generally used for 3 months or more necessitated carcinogenicity studies. In Europe, the Rules Governing Medicinal Products in the European Community defined the circumstances when carcinogenicity studies were required. These circumstances included administration over a substantial period of life, i.e., continuously during a minimum period of 6 months or frequently in an intermittent manner so that the total exposure was similar.III.OBJECTIVE OF THE GUIDELINE (3)The objective of this guideline is to define the conditions under which carcinogenicity studies should be conducted to avoid the unnecessary use of animals in testing, and to provideconsistency in worldwide regulatory assessments of applications. It is expected that these studies will be performed in a manner that reflects currently accepted scientific standards.The fundamental considerations in assessing the need for carcinogenicity studies are the maximum duration of patient treatment and any perceived cause for concern arising from otherinvestigations. Other factors may also be considered such as the intended patient population,prior assessment of carcinogenic potential, the extent of systemic exposure, the (dis)similarity to endogenous substances, the appropriate study design, or the timing of study performance relative to clinical development.IV.FACTORS TO CONSIDER FOR CARCINOGENICITY TESTING (4)A.Duration and Exposure (4.1)Carcinogenicity studies should be performed for any pharmaceutical whose expectedclinical use is continuous for at least 6 months.2Certain classes of compounds may not be used continuously over a minimum of 6 months but may be expected to be used repeatedly in an intermittent manner. It is difficult todetermine and to justify scientifically what time represents a clinically relevant treatment period for frequent use with regard to carcinogenic potential, especially for discontinuous treatment periods. For pharmaceuticals used frequently in an intermittent manner in the treatment of chronic or recurrent conditions, carcinogenicity studies are generally needed. Examples of such conditions include allergic rhinitis, depression, and anxiety.Carcinogenicity studies may also need to be considered for certain delivery systems which may result in prolonged exposures. Pharmaceuticals administered infrequently or for shortduration of exposure (e.g., anesthetics and radiolabeled imaging agents) do not need carcinogenicity studies unless there is cause for concern.B.Cause for Concern (4.2)Carcinogenicity studies may be recommended for some pharmaceuticals if there is concern about their carcinogenic potential. Criteria for defining these cases should be very carefully considered because this is the most important reason to conduct carcinogenicity studies for most categories of pharmaceuticals. Several factors which could be considered may include:1.previous demonstration of carcinogenic potential in the product class thatis considered relevant to humans;2.structure-activity relationship suggesting carcinogenic risk;3.evidence of preneoplastic lesions in repeated dose toxicity studies; and4.long-term tissue retention of parent compound or metabolite(s) resulting inlocal tissue reactions or other pathophysiological responses.C.Genotoxicity (4.3)Unequivocally genotoxic compounds, in the absence of other data, are presumed to be transspecies carcinogens, implying a hazard to humans. Such compounds need not be subjected to long-term carcinogenicity studies. However, if such a drug is intended to be administered chronically to humans, a chronic toxicity study (up to 1 year) may be necessary to detect early tumorigenic effects.Assessment of the genotoxic potential of a compound should take into account the totality of the findings and acknowledge the intrinsic value and limitations of both in vitro and in vivo tests. The test battery approach of in vitro and in vivo tests is designed to reduce the risk of false negative results for compounds with genotoxic potential. A single positive result in any assay for genotoxicity does not necessarily mean that the test compound poses a genotoxic hazard to humans (see the ICH Guideline on Specific Aspects of Regulatory Genotoxicity Tests).D.Indication and Patient Population (4.4)When carcinogenicity studies are required they usually need to be completed before application for marketing approval. However, completed rodent carcinogenicity studies3are not needed in advance of the conduct of large scale clinical trials unless there is special concern for the patient population.For pharmaceuticals developed to treat certain serious diseases, carcinogenicity testing need not be conducted before market approval although these studies should be conducted post-approval. This speeds the availability of pharmaceuticals for life-threatening or severely debilitating diseases, especially where no satisfactory alternative therapy exists.In instances where the life-expectancy in the indicated population is short (i.e., less than 2 to 3 years), no long-term carcinogenicity studies may be required. For example, oncolytic agents intended for treatment of advanced systemic disease do not generally need carcinogenicity studies. In cases where the therapeutic agent for cancer is generally successful and life is significantly prolonged, there may be later concerns regarding secondary cancers. When such pharmaceuticals are intended for adjuvant therapy in tumor free patients or for prolonged use in noncancer indications, carcinogenicity studies are usually needed.E.Route of Exposure (4.5)The route of exposure in animals should be the same as the intended clinical route when feasible (see the ICH Guideline on Dose Selection for Carcinogenicity Studies of Pharmaceuticals). If similar metabolism and systemic exposure can be demonstrated by differing routes of administration, carcinogenicity studies should only be conducted by a single route, recognizing that it is important that relevant organs for the clinical route (e.g., lung for inhalational agents) be adequately exposed to the test material. Evidence of adequate exposure may be derived from pharmacokinetic data (see the ICH Guideline on Repeated Dose Tissue Distribution Studies).F.Extent of Systemic Exposure (4.6)Pharmaceuticals applied topically (e.g., dermal and ocular routes of administration) may need carcinogenicity studies. Pharmaceuticals showing poor systemic exposure from topical routes in humans may not need studies by the oral route to assess the carcinogenic potential to internal organs. Where there is cause for concern for photocarcinogenic potential, carcinogenicity studies by dermal application (generally in mice) may be needed. Pharmaceuticals administered by the ocular route may not need carcinogenicity studies unless there is cause for concern or unless there is significant systemic exposure.For different salts, acids, or bases of the same therapeutic moiety, where prior carcinogenicity studies are available, evidence should be provided that there are no significant changes in pharmacokinetics, pharmacodynamics, or toxicity. When changes in exposure and consequent toxicity are noted, additional bridging studies may be used to determine whether additional carcinogenicity studies are needed. For esters and complex4derivatives, similar data would be valuable in assessing the need for an additionalcarcinogenicity study, but this should be considered on a case-by-case basis.G.Endogenous Peptides and Protein Substances or Their Analogs (4.7)Endogenous peptides or proteins and their analogs produced by chemical synthesis, byextraction/purification from an animal/human source, or by biotechnological methods such as recombinant DNA technology, may require special considerations.Carcinogenicity studies are not generally needed for endogenous substances givenessentially as replacement therapy (i.e., physiological levels), particularly where there isprevious clinical experience with similar products (e.g., animal insulins, pituitary-derived growth hormone, and calcitonin).Although not usually necessary, long-term carcinogenicity studies in rodent species should be considered for the other biotechnology products noted above if indicated by thetreatment duration, clinical indication, or patient population (provided neutralizingantibodies are not elicited to such an extent in repeated dose studies as to invalidate theresults). Conduct of carcinogenicity studies may be important in the followingcircumstances:1.for products where there are significant differences in biological effects tothe natural counterpart(s);2.for products where modifications lead to significant changes in structurecompared to the natural counterpart; and3.for products resulting in humans in a significant increase over the existinglocal or systemic concentration (i.e., pharmacological levels).V.NEED FOR ADDITIONAL TESTING (5)The relevance of the results obtained from animal carcinogenicity studies for assessment of human safety are often cause for debate. Further research may be needed, investigating the mode of action, which may result in confirming the presence or the lack of carcinogenic potential for humans. Mechanistic studies are useful to evaluate the relevance of tumor findings in animals for human safety.5。

请将以下中文翻译成英文国际临床和实验室标准协会（CLSI）原名美国临床实验室标准化委员会（NCCLS），自1967年成立以来，致力于“为检验结果的一致性建立标准”。

迄今为止，为临床实验室已提供超过160项标准和指南，涉及到当今检验医学发展的方方面面，包括保健服务、自动化和信息学、临床化学和毒理学、血液学、免疫学和配体分析、微生物学、分子生物学、床旁检测、临床实验室国家参考系统等。

同时，CLSI与世界相关的权威机构如国际标准化组织（ISO）、国际临床化学协会（IFCC）、国际血液学标准化委员会（ICSH）等机构密切合作，为全球的检验医学和卫生技术标准的一致性做出了不懈努力。

随着所建立标准和指南越来越多，CLSI对全球检验医学的影响日益增大，其已被全球检验医生界所接受，现已拥有会员组织超过2000家。

同时CLSI定义为一个全球性、非赢利、致力于标准建立和开发的组织。

CLSI基于大家认同的一致性标准具有效率高、成本低的原则，促进医疗保健团体自自愿使用具有一致性的标准和指南，以改善对受检者的检测和服务。

International Clinical and Laboratory Standards Institute CLSI)NCCLS, formerly known as U.S. Committee for Clinical Laboratory Standards, since its inception in 1967, has committed to "establishing standards for consistency of the test results."So far, the clinical laboratory has provided more than 160 standards and guidelines, relating to the development of all aspects of laboratory medicine today which include health services, automation and informatics, clinical chemistry and toxicology, hematology, immunology and ligand analysis, microbiology, molecular biology, bedside testing, clinical laboratory National Reference systems, etc.Meanwhile, CLSI has close cooperation with the world authority such as the International Organization for Standardization (ISO), the International Association of Clinical Chemistry (IFCC), the International Committee for Standardization in Hematology (ICSH) and other agencies, making unremitting efforts for the global consistency in laboratory medicine and health technology standards .With more and more establishment of standards and guidelines, CLSI, which has been accepted by the global community examining physician, has an increasing effect on the global laboratory medicine .Now it owns more than 2,000 member organizations. Meanwhile CLSI is defined as a global, non-profit organization dedicating to the establishment and development of standards. CLSI has the principle of high efficiency and low cost which was based on the consistency criteria that we all agree with and promotes health care organizations from the voluntary use of consistent standards and guidelines to improve the detection of subjects and services.。

Guidelines for Drinking-water Quality（世界卫生组织饮用水质量指导标准第四版）Guidelines forDrinking-water QualityFOURTH EDITION WHO Library Cataloguing-in-Publication DataGuidelines for drinking-water quality - 4thed1Potable water - standards 2Water - standards 3Water quality - standards4Guidelines IWorld Health OrganizationISBN 978 92 4 154815 1 NLM classifcation WA 675World Health Organization 7>2011All rights reserved Publications of the World Health Organization are available on the WHO web sitehttpcom or can be purchased from WHO Press World Health Organization 20 Avenue Appia1211 Geneva 27 Switzerland tel 41 22 791 3264 fax 41 22 791 4857 e-mail bookorderswhointRequests for permission to reproduce or translate WHO publications –whether for sale or for non-commercial distribution –should be addressed to WHO Press through the WHO web site httpwhointaboutlicensingcopyright_formenindexhtmlThe designations employed and the presentation of the material in this publication do not imply theexpression of any opinion whatsoever on the part of the World Health Organization concerning the legalstatus of any country territory city or area or of its authorities or concerning the delimitation of itsfrontiers or boundaries Dotted lines on maps represent approximate border lines for which there may notyet be full agreementThe mention of specifc companies or of certain manufacturersproducts does not imply that they areendorsed or recommended by the World Health Organization in preference to others of a similar naturethat are not mentioned Errors and omissions excepted the names of proprietary products are distinguishedby initial capital lettersAll reasonable precautions have been taken by the World Health Organization to verify the informationcontained in this publication However the published material isbeing distributed without warranty of anykind either expressed or implied The responsibility for the interpretation and use of the material lies withthe reader In no event shall the World Health Organization be liable for damages arising from its useCover designed by WHO Graphics SwitzerlandTypeset by Value Chain IndiaPrinted in Malta by GutenbergiiiContentsPreface xvAcknowledgements xviiAcronyms and abbreviations used in text xx1 Introduction 111 General considerations and principles 1com Framework for safe drinking-water 3com Microbial aspects 4com Disinfection 5com Chemical aspects 6com Radiological aspects 7com Acceptability aspects taste odour and appearance 712 Roles and responsibilities in drinking-water safety management 8com Surveillance and quality control 8com Public health authorities 10com Local authorities 11com Water resource management 12com Drinking-water supply agencies 13com Community management 14com Water vendors 15com Individual consumers 15com Certifcation agencies 15com Plumbing 1613 Supporting resources to the Guidelines 18com Published documents 18com Capacity-building networks 182 A conceptual framework for implementing the Guidelines 1921 Health-based targets 2022 Water safety plans 22com System assessment and design 22com Operational monitoring 23com Management plans documentation and communication 24iv GUIDELINES FOR DRINKING-WATER QUALITY23 Surveillance 25。

肺癌免疫治疗指南2021中文版英文回答：Lung Cancer Immunotherapy Guideline (2021)。

Introduction.Immunotherapy is a promising cancer treatment approach that utilizes the body's immune system to fight cancer cells. The recent advancements in immunotherapy have revolutionized the treatment landscape for lung cancer, offering hope for patients with advanced disease.Indications for Immunotherapy in Lung Cancer.Metastatic non-small cell lung cancer (NSCLC) without actionable mutations.Recurrent NSCLC after platinum-based chemotherapy.Stage IIIA or IIIB NSCLC after adjuvant chemotherapy.Small cell lung cancer (SCLC) as first-line therapy.Types of Immunotherapy.Immune checkpoint inhibitors: These drugs block immune checkpoints, which are molecules that inhibit the immune system's response to cancer cells. The most commonly used checkpoint inhibitors target PD-1, PD-L1, or CTLA-4.Adoptive cell therapy: This approach involves modifying the patient's own immune cells (T cells) to enhance their ability to recognize and attack cancer cells.Treatment Regimens.The optimal immunotherapy regimen for lung cancer depends on the stage of the disease, patient characteristics, and response to prior treatments.First-line treatment: For metastatic NSCLC withoutactionable mutations, the recommended first-line treatment is immune checkpoint inhibitors alone or in combination with chemotherapy.Recurrent disease: For recurrent NSCLC after platinum-based chemotherapy, the recommended treatment is immune checkpoint inhibitors alone or in combination with a different chemotherapy regimen.Adjuvant setting: For stage IIIA or IIIB NSCLC after adjuvant chemotherapy, immune checkpoint inhibitors may be considered as maintenance therapy to reduce the risk of recurrence.SCLC: For SCLC, the recommended first-line treatment is immune checkpoint inhibitors in combination with chemotherapy.Patient Selection.The selection of patients for immunotherapy in lung cancer depends on several factors, including:PD-L1 expression on tumor cells.Presence of tumor-infiltrating lymphocytes (TILs)。

guideline for good clinical practice -回复Guideline for Good Clinical Practice (GCP): Ensuring Ethical and Quality Clinical TrialsIntroduction:The Guideline for Good Clinical Practice (GCP) is an international ethical and scientific quality standard that sets guidelines for designing, conducting, recording, and reporting clinical trials involving human subjects. GCP ensures the rights, safety, andwell-being of participants and provides reliable clinical trial data for regulatory submission and evidence-based medicine. In this article, we will explore the various steps involved in adhering to GCP guidelines.Step 1: Study Design and Protocol DevelopmentThe first step in conducting a clinical trial in accordance with GCP is to design a study that addresses the research question effectively. The research team should develop a detailed protocol that outlines the trial's objectives, study population, inclusion and exclusion criteria, treatment regimens, study duration, and assessment methods.Step 2: Selection and Recruitment of ParticipantsThe fair selection and recruitment of participants is crucial in maintaining the ethical principles of GCP. Investigators must obtain informed consent from potential participants after providing them with comprehensive information regarding the trial objectives, risks, benefits, and expected outcomes. Participants should have the right to withdraw from the study at any time without prejudice.Step 3: Ethical Review and ApprovalBefore commencing the trial, the research protocol must undergo ethical review and obtain approval from an independent ethics committee or Institutional Review Board (IRB). This ensures that the trial meets ethical principles and protects the rights, safety, and well-being of participants.Step 4: Training and QualificationAll individuals involved in the conduct of the trial, including investigators, study coordinators, and other research staff, should receive appropriate training and qualifications. This ensures that they understand the principles of GCP and are competent in conducting trial-related tasks, maintaining data integrity, and handling adverse events.Step 5: Trial Documentation and Data ManagementGCP emphasizes the importance of maintaining accurate and complete trial documentation. This includes the development of case report forms (CRFs) to collect participant data, informed consent forms, protocol amendments, drug accountability records, and study reports. Additionally, procedures for data handling, storage, and archiving must be implemented.Step 6: Safety Monitoring and ReportingThe safety of participants is paramount in clinical trials. Investigators must establish mechanisms to identify, evaluate, and manage adverse events effectively. Any unexpected or serious adverse events should be promptly reported to the relevant authorities, ethics committees, and trial sponsors.Step 7: Quality Control and Quality AssuranceQuality control and quality assurance (QA) measures should be implemented to ensure trial conduct and data integrity. QA involves independent audits, inspections, and evaluations to verify compliance with GCP requirements. These actions help ensure that the study is conducted in compliance with protocols, regulations,and ethical principles.Step 8: Statistical Analysis and ReportingThe trial's statistical analysis plan should be pre-defined to address the primary and secondary research questions. Statistical methods must conform to accepted standards to ensure unbiased analysis. The trial results should be reported accurately and transparently, whether they are positive or negative, with appropriate discussion and interpretation.Step 9: Trial Closure and ReportingUpon trial completion or premature termination, the research team should close the trial promptly. The final trial report should include findings and conclusions, adhering to GCP principles. Trial sponsors are expected to facilitate the dissemination of trial results to ensure transparency and contribute to scientific knowledge.Conclusion:Adhering to the Guideline for Good Clinical Practice (GCP) is essential to conduct ethical and quality clinical trials. From study design and participant recruitment to data management andreporting, each step must follow the principles of GCP to protect participant rights, ensure trial integrity, and generate reliable scientific evidence. Compliance with GCP guidelines is crucial to advancing medical research and improving patient care.。

生物多样性　第7卷,第2期,1999年5月CHIN ESE BIODIV ERSIT Y　7(2):151～155,May,1999终止子技术与生物安全Ξ钱迎倩　马克平　桑卫国　魏　伟ΞΞ(中国科学院植物研究所,北京　100093)摘　要　终止子技术是美国Delta and Pine Land种子公司和美国农业部联合申请、经美国专利局1998年3月批准的一项专利。

整个过程可叙述为遗传工程师在转基因作物中加入了由3个基因组成的终止子基因;得到的转基因作物的种子由种子公司加上一种诱导剂;经诱导剂的作用及终止子基因间的相互作用,在种子胚胎发育的后期产生一种毒素;这种毒素杀死了发育后期的胚胎;最后得到的是成熟但不育的种子。

专利获得后,引起国际上巨大反响。

国际农业研究磋商小组指出,终止子技术必须禁止,不然将给全球食品保障带来影响。

原因是这项技术会使农民无法留种、对遗传多样性有负影响,由于农民不再育种影响到持续农业的发展,可能出现出售或交换不能发芽的种子以及通过花粉非故意的传播造成生物安全的风险。

第三世界国家认为这项技术是“种子的灾难”、“农业上的中子弹”。

虽然转基因作物产生不育种子可能在解决转基因逃逸带来的生态风险上有益处,但这个收获与终止子技术可能给全球食品保障带来危机相比,两者就不能等量齐观了。

从另一角度看,这项技术可能又是遗传工程带来的另一种生物安全危机。

关键词　终止子技术,不育种子,基因保护,“种子的灾难”,生物安全T erminator technology and biosafety/QIAN Ying2Q ian,MA K e2Ping,SANG Wei2G uo,WEI WeiΞΞAbstract　In March1998,the Delta and Pine Land seed com pany and the U.S.Department of Agriculture announced that they had received a patent on the“Terminator Technology”.The technology involves three fol2 lowing steps:genetic engineers transfer terminator genes to a crop;the seed company initiates the terminator process by adding an inducer before selling the seeds;farmers then plant seeds,and harvest mature,but ster2 ile,seeds.At a late stage of seed development,under the control of the inducer,one gene in the terminator be2 comes active and produces toxin.The toxin kills the embryo,resulting in the sterile seed.Enormous interna2 tional responses were induced by this patent.The Consultative Grou p on International Agricultural Research (CGIAR)pointed out that the terminator technology must be banned in order to defend the world food securi2 ty.The CGIAR cited the following reasons:This technology will stop farmers from producing fertile seeds from their own crops,consequently,the genetic diversity of crops and sustainabity of agriculture will be ad2 versely affected.It will probably induce the risk of the sale or exchange of sterile seeds,and risk of biosafety through pollen spread.S ome third world countries warmed that this technique is“seeds of disaster”,and“the neutron bomb of agriculture”.Sterile seeds produced by genetically modified crops with terminator genes may solve the ecological risk brought about from transgene escape,but the accompanied risk on biosafety and ex2 pense of global food security is no solution.From another point of view,this technology itself may be the an2 other kind of risk of biosafety derived from genetic engineering.K ey w ords　terminator technology,sterile seed,gene protection,“seeds of disaster”,biosafetyAuthor’s address　Institute of Botany,The Chinese Academy of Sciences,China100093用遗传工程手段得到的经修饰活生物体(LMO)向环境释放后可能产生一系列生态风险,Ξ收稿日期:1999-02-09;修改稿收到日期:1999-03-15Ξ九五国家重点科技项目(攻关)计划(97-925-02-04-05)资助Supported by a K ey Project of the Ninth Five Y ears Plan of Science and Technology Commission(97-925-02-04-05)ΞΞ现在地址:中国农业大学农业生物技术国家重点实验室,北京,100094Present address:National Laboratories for Agro-Biotechnology,China Agricultural University,Beijing,100094251生　物　多　样　性 第7卷其中已被实验证明了的风险是转基因的逃逸[1,2],从而可能使转基因作物的野生近缘种成为杂草。