OBJECTIVE To further standardize the technical operations and management processes throughout therapeutic drug monitoring （TDM）， clarify the clinical value of TDM implementation， improve the scientific validity and reliability of monitoring results， and provide a solid reference basis for the formulation and optimization of clinical individualized precision dosing regimens. METHODS The Guidelines for the Management of Therapeutic Drug Monitoring were formulated in accordance with the latest definition of guidelines by the Institute of Medicine of the National Academies and the standard guideline development methodology of the World Health Organization， and in compliance with the requirements of the appraisal of guidelines for research and evaluation. A modified Delphi method was adopted to establish the research question system； evidence-based medicine research methods were applied to systematically search multiple databases to screen the latest and most comprehensive evidence. Evidence was graded and evaluated based on the evidence grading system of the Chinese Evidence-Based Medicine Center， and the grading criteria for recommendation strength from the Oxford Centre for Evidence-Based Medicine were used to determine the recommendation strength. The recommendation opinions were formed through multidisciplinary expert consensus. RESULTS The Guidelines for the Management of Therapeutic Drug Monitoring cover four core modules， including TDM application indications， technical procedures， result interpretation and clinical application， and quality control， involving 18 primary research questions， 34 secondary research questions， and yield 82 recommendations. CONCLUSIONS The guidelines systematically standardize the key technical links and management requirements of the whole TDM process， provide scientific and operable standardized tools， help improve the standardization level of TDM work， promote the translation of monitoring results into clinical decision-making， and provide strong support for precision personalized medicine and ensuring the safety and rationality of medication use.

With the rapid development of clinical trials, the relevant medical research and molecular detection based on biological samples are closely related to the progress of clinical trials, making the role of biological samples in clinical trials increasingly obvious. The standardized supervision mode of biological samples is an important prerequisite for carrying out high-quality clinical trials. Although the laws and regulations related to clinical trials are becoming more and more perfect, there are still a large number of adverse events related to biological samples, which seriously affects the progress and results of clinical trials, and is one of the important challenges currently facing. Therefore, it is urgent to enhance the supervision of biological samples and improve the management methods of biological samples in clinical trials at this stage. Through in-depth discussion of the current status of biological sample management in clinical trials at home and abroad, this paper analyzed the issues existed during the supervision of biological samples, and supplemented the biological sample management methods by further combing the existing relevant laws and regulations and the Guidelines for the Ethical Management of Biological Samples in Clinical Trials, with a view to providing suggestions and ideas for optimizing the management mode of biological samples in clinical trials.

BACKGROUND: Deposition of beta-amyloid protein is the main cause of Alzheimer disease. Overexpression of β-amyloid precursor protein gene (βAPP-gene) or mutation of it at certain part can be related with the attack of Alzheimer disease.OBJECTIVE: To observe the relationship of Alzheimer disease and β-amyloid protein with β APP-gene in Yimeng mountainous area.DESIGN: A case-control analysis study.SETTING: Department of Neurology, Linyi Municipal People's Hospital.PARTICIPANTS: Thirty-two Alzheimer disease inpatients were enrolled at the Department of Neurology, Linyi Municipal People's Hospital affiliated to Linyi Medical Professional College between January 2001 and December 2003. Thirty elderly patients who were treated with surgery of noncraniocerebral injury and were of the same sex and the similar age were regarded as the members of the control group [score of Mini Mental State Examination (MMSE) was over 27 points].METHODS: Level of β-amyloid protein in cerebrospinal fluid was detected with enzyme-linked immunoadsordent assay (ELISA). Expression of βAPP-gene was measured with the technic of fluorescent quantitative polymerase chain reaction.RESULTS: A total of 62 cases were involved in the result analysis. ①The level of β-amyloid protein in cerebrospinal fluid in the Alzheimer disease group was higher significantly than that in the control group[(13.63±9.34), (6.75±5.37)μg/L,t=3.354, P ＜ 0.01]. ② The expression ofβ APP in cerebrospinal fluid in the Alzheimer disease group was higher significantly than that in the control group [(1 624±298), (1275±269)copy/μL,t=4.42, P ＜ 0.01]. ③ The level of β-amyloid protein was posit ively correlated with the expression of β APP-gene in the Alzheimer disease group (r=0.44,P＜ 0.01).CONCLUSION: The level of β-amyloid protein and the expression of β APP-gene in cerebrospinal fluid of Alzheimer disease patients in the Yimeng Mountainous area increase. Besides, the higher the level of β-amyloid protein, the higher the expression of β APP-gene is, and the severer the degree of dementia is. It indicates that Alzheimer disease has closely relation with β-amyloid protein and β APP-gene. But the expression of the β APP-gene has no specificity in the diagnosis of Alzheimer disease.