OBJECTIVE To standardize the main processes and related technical links of the clinical comprehensive evaluation of drugs， and provide guidance and reference for improving the quality of comprehensive evaluation evidence and its transformation and application value. METHODS The construction of Guideline for the Workflow of Clinical Comprehensive Evaluation of Drugs was based on the standard guideline formulation method of the World Health Organization （WHO）， strictly followed the latest definition of guidelines by the Institute of Medicine of the National Academy of Sciences of the United States， and conformed to the six major areas of the Guideline Research and Evaluation Tool Ⅱ. Delphi method was adopted to construct the research questions； research evidence was established by applying the research methods of evidence-based medicine. The evidence quality classification system of the Chinese Evidence-Based Medicine Center was adopted for evidence classification and evaluation. The recommendation strength was determined by the recommendation strength classification standard formulated by the Oxford University Evidence-Based Medicine Center， and the recommendation opinions were formed through the expert consensus method. RESULTS & CONCLUSIONS The Guideline for the Workflow of Clinical Comprehensive Evaluation of Drugs covers 4 major categories of research questions， including topic selection， evaluation implementation， evidence evaluation， and application and transformation of results. The formulation of this guideline has standardized the technical links of the entire process of clinical comprehensive evaluation of drugs， which can effectively guide the high-quality and high-efficient development of this work， enhance the standardized output and transformation application value of evaluation evidence， and provide high-quality evidence support for the scientific decision-making of health and the rationalization of clinical medication.

OBJECTIVE To analyze the risk factors of substandard drug blood concentration of meropenem in patients with hospital acquired pneumonia （HAP）. METHODS Totally 130 HAP patients who were admitted to the intensive care unit of Suzhou Hospital Affiliated to Nanjing Medical University from January 2020 to June 2021 and received steady -state blood concentration test of meropenem were selected as the study subjects . The patient ’s age ，sex，body mass and other medical history were recorded . The steady-state blood trough concentration of meropenem was determined and its target was determined . Univariate and multivariate Logistic regression analysis were used to screen the risk factors for the substandard steady -state blood trough concentration of meropenem. The receiver operating characteristic （ROC）curve was drawn to screen the warning value of the risk factors and evaluate the predictive value of the risk factors . RESULTS The steady -state blood trough concentrations of 85 cases were ≥2 mg/L， and those of 45 cases were ＜2 mg/L. Multivariate Logistic regression analysis showed that age ，negative balance and brain injury were independent risk factors for the substandard steady-state blood trough concentration of meropenem （P＜ 0.05）.ROC curve showed that when the patient was 58 years old，the area under the ROC curve was the largest （0.744）， the sensitivity was 0.882，the specificity was 0.556，and the Youden index was 0.438；when the negative balance was 520.5 mL/24 h，the area under the ROC curve reached the maximum （0.827），the sensitivity was 0.722，the specificity was 0.905，and th e Youden index was 0.628. The creatinine clearance rate in the brain injury group was significantly higher than that in the non -brain injury group ，and the steady -state blood trough concentration of meropenem in the brain injury group was significantly lower than that in the non -brain injury group （P＜0.001）. CONCLUSIONS When the HAP patient ’s age is less than 58 years old ，the brain injury and the negative balance is more than 520.5 mL/24 h，the risk of substandard steady -state blood trough concentration of meropenem will increase .

Objective To optimize the extraction process of main iridoid glycosides in Damnacanthus officinarum Huang and evaluate the antioxidant activity of Damnacanthus officinarum Huang in vitro. Methods The classical heating-reflux extraction method was selected. The volume fraction of ethanol, the volume of solvent and extraction time were taken as the evaluation factors. The comprehensive score of extraction yield and the monotropein content were used as the evaluation indexes. An orthogonal test was designed to select the best extraction conditions. The total reducing capacity, DPPH clearance rate and hydroxyl radical scavenging rate were measured to determine its antioxidant activity in vitro. Results The optimal extraction process was the reflux with 6 times volume of 60% ethanol for 2 hours. Damnacanthus officinarum Huang has certain antioxidant capacity, and the activity of ethyl acetate part had the best effect. Conclusion The optimized extraction process is stable and feasible, which can be used for extraction of the iridoid glycosides from Damnacanthus officinarum Huang. This study has proved that Damnacanthus officinarum Huang has certain antioxidant activity.

Objective: To investigate the relationship of sleep duration and sleep quality with anxiety in the elderly aged 60 years and older in China. Methods: The elderly aged 60 years and older were selected from the China Short-term Health Effects of Air Pollution Study conducted between July 18, 2017 and February 7, 2018. Multivariate logistic regression models were used to analyze the association of sleep duration and sleep quality with anxiety. Results: A total of 3 897 elderly aged 60 years and older were included in the study. The age of the elderly was (73.4±8.0) years old. Among the elderly surveyed, 6.5% were defined with anxiety, and 18.7% reported poor sleep quality. Multivariate logistic regression models showed shorter sleep duration was the risk factor for anxiety in the elderly that after adjusting for factors such as general demographics, socioeconomic factors, lifestyle, health status, social support and ambient fine particulates exposure. Compared with the elderly with 7 hours of sleep duration daily, the OR (95%CI) of anxiety for those with sleep duration ≤ 6 hours was 2.09 (1.49-2.93). Compared with those with good sleep quality, the OR (95%CI) of anxiety for those with poor sleep quality was 5.12 (3.88-6.77). We also found statistically significant correlations of the scores of subscales of Pittsburgh sleep quality index with anxiety, in which the effects of sleep disturbance, subjective sleep quality and daytime dysfunction scores were most obvious, the ORs (95%CI) were 4.63 (3.55-6.04), 2.75 (2.33-3.23) and 2.50 (2.19-2.86), respectively. Subgroup analysis showed that the association of sleep duration and sleep quality with anxiety was more obvious in males and in those aged <80 years. Conclusion Shorter sleep duration and poor sleep quality are associated with anxiety in the elderly in China.

Objective: To analyze influencing factors for depressive symptoms in the elderly aged 65 years and older in 8 longevity areas in China. Methods: We recruited 2 180 participants aged 65 years and older in 8 longevity areas from Healthy Aging and Biomarkers Cohort Study, a sub-cohort of the Chinese Longitudinal Healthy Longevity Survey in 2017. Multivariate logistic regression analysis was performed to evaluate the relationships of socio-demographic characteristics, behavioral lifestyle, chronic disease prevalence, functional status, family and social support with depressive symptoms in the elderly. Results: The detection rate of depression symptoms was 15.0% in the elderly aged 65 years and older in 8 longevity areas of China, and the detection rate of depression symptoms was 11.5% in men and 18.5% in women. Multivariate logistic regression analysis results showed that the detection rate of depressive symptoms was lower in the elderly who had regular physical exercises (OR=0.44, 95%CI: 0.26-0.74), frequent fish intakes (OR=0.57, 95%CI: 0.39-0.83), recreational activities (OR=0.65, 95%CI: 0.44-0.96), social activities (OR=0.28, 95%CI: 0.11-0.73) and community services (OR=0.68, 95%CI: 0.50-0.93). The elderly who were lack of sleep (OR=2.04, 95%CI: 1.49-2.80), had visual impairment (OR=1.54, 95%CI: 1.08-2.18), had gastrointestinal ulcer (OR=2.97, 95%CI: 1.53-5.77), had arthritis (OR=2.63, 95%CI: 1.61-4.32), had higher family expenditure than income (OR=1.80, 95%CI: 1.17-2.78) and were in poor economic condition (OR=4.58, 95%CI: 2.48-8.47) had higher detection rate of depressive symptoms. Conclusion The status of doing physical exercise, fish intake in diet, social activity participation, sleep quality or vision, and the prevalence of gastrointestinal ulcers and arthritis were associated with the detection rate of depressive symptoms in the elderly.

Objective: To establish a prediction model for 6-year incidence risk of chronic kidney disease (CKD) in the elderly aged 65 years and older in China. Methods: In this prospective cohort study, we used the data of 3 742 participants collected during 2008/2009-2014 and during 2012-2017/2018 from Healthy Aging and Biomarkers Cohort Study, a sub-cohort of the Chinese Longitudinal Healthy Longevity Survey. Two follow up surveys for renal function were successfully conducted for 1 055 participants without CKD in baseline survey. Lasso method was used for the selection of risk factors. The risk prediction model of CKD was established by using Cox proportional hazards regression models and visualized through nomogram tool. Bootstrap method (1 000 resample) was used for internal validation, and the performance of the model was assessed by C-index and calibration curve. Results: The mean age of participants was (80.8±11.4) years. In 4 797 person years of follow up, CKD was found in 262 participants (24.8%). Age, BMI, sex, education level, marital status, having retirement pension or insurance, hypertension prevalence, blood uric acid, blood urea nitrogen and total cholesterol levels and estimated glomerular filtration rate in baseline survey were used in the model to predict the 6-year incidence risk of CKD in the elderly. The corrected C-index was 0.766, the calibration curve showed good consistence between predicted probability and observed probability in high risk group, but relatively poor consistence in low risk group. Conclusion The incidence risk prediction model of CKD established in this study has a good performance, and the nomogram can be used as visualization tool to predict the 6-year risk of CKD in the elderly aged 65 years and older in China.

Objective: To investigate the relationship of plasma albumin and hypersensitive C-reactive protein (Hs-CRP) with 5-year all-cause mortality among Chinese older adults aged 65 and older. Method: Data was collected in 8 longevity areas of the Chinese Longitudinal Healthy Longevity Survey (CLHLS) study conducted by Chinese Center for Disease Control and Prevention and Peking University at baseline survey in 2012 and 2014, the participants enrolled in 2012 was followed-up in 2014 and 2017, the participants enrolled in 2014 was followed-up in 2017 only. Finally, 3 118 older adults aged 65 and older with complete information on albumin, Hs-CRP and body mass index (BMI) were included in this study. Plasma samples of older adults were collected for the detection of albumin and Hs-CRP at baseline survey. Survival status and follow-up time was recorded for all participants. All older adults were divided into 4 groups according to the levels of plasma albumin and Hs-CRP, and Cox proportional hazard models were constructed to assess their influence on the risk of all-cause mortality. Results: Among 3 118 older adults included, the prevalence of hypoalbuminemia was 10.1% (316/3 118), and was 22.8% (711/3 118) for elevated Hs-CRP. During 10 132 person-years of follow-up, 1 212 participants died. Participants with hypoalbuminemia had increased risk of all-cause mortality, with an hazard ratio (HR) and 95% confidential interval (CI) of 1.18 (1.01-1.38), compared to participants with normal plasma albuminemia; participants with elevated Hs-CRP had increased risk of all-cause mortality, with an HR (95%CI) of 1.18 (1.04-1.35), compared to participants with normal plasma Hs-CRP. Participants with normal plasma albumin and elevated Hs-CRP, with hypoalbuminemia and normal Hs-CRP, with hypoalbuminemia and elevated Hs-CRP also had increased risk of all-cause mortality when compared to those with normal plasma albumin and normal Hs-CRP, the HR (95%CI) were 1.16 (1.01-1.34), 1.11 (0.91-1.37) and 1.43 (1.11-1.83), respectively. Conclusion Hypoalbuminemia and elevated Hs-CRP were responsible for increased risk of 5-year all-cause mortality among Chinese older adults from 8 longevity areas.

Objective To investigate the relationship of plasma albumin and hypersensitive C?reactive protein (Hs?CRP) with 5?year all?cause mortality among Chinese older adults aged 65 and older. Method Data was collected in 8 longevity areas of the Chinese Longitudinal Healthy Longevity Survey (CLHLS) study conducted by Chinese Center for Disease Control and Prevention and Peking University at baseline survey in 2012 and 2014, the participants enrolled in 2012 was followed?up in 2014 and 2017, the participants enrolled in 2014 was followed?up in 2017 only. Finally, 3 118 older adults aged 65 and older with complete information on albumin, Hs?CRP and body mass index (BMI) were included in this study. Plasma samples of older adults were collected for the detection of albumin and Hs?CRP at baseline survey. Survival status and follow?up time was recorded for all participants. All older adults were divided into 4 groups according to the levels of plasma albumin and Hs?CRP, and Cox proportional hazard models were constructed to assess their influence on the risk of all?cause mortality. Results Among 3 118 older adults included, the prevalence of hypoalbuminemia was 10.1% (316/3 118), and was 22.8% (711/3 118) for elevated Hs?CRP. During 10 132 person?years of follow?up, 1 212 participants died. Participants with hypoalbuminemia had increased risk of all?cause mortality, with an hazard ratio (HR) and 95% confidential interval (CI) of 1.18 (1.01-1.38), compared to participants with normal plasma albuminemia; participants with elevated Hs?CRP had increased risk of all?cause mortality, with an HR (95%CI) of 1.18 (1.04-1.35), compared to participants with normal plasma Hs?CRP. Participants with normal plasma albumin and elevated Hs?CRP, with hypoalbuminemia and normal Hs?CRP, with hypoalbuminemia and elevated Hs?CRP also had increased risk of all?cause mortality when compared to those with normal plasma albumin and normal Hs?CRP, the HR (95%CI) were 1.16 (1.01-1.34), 1.11 (0.91-1.37) and 1.43 (1.11-1.83), respectively. Conclusion Hypoalbuminemia and elevated Hs?CRP were responsible for increased risk of 5?year all?cause mortality among Chinese older adults from 8 longevity areas.

Objective To investigate the relationship of plasma albumin and hypersensitive C?reactive protein (Hs?CRP) with 5?year all?cause mortality among Chinese older adults aged 65 and older. Method Data was collected in 8 longevity areas of the Chinese Longitudinal Healthy Longevity Survey (CLHLS) study conducted by Chinese Center for Disease Control and Prevention and Peking University at baseline survey in 2012 and 2014, the participants enrolled in 2012 was followed?up in 2014 and 2017, the participants enrolled in 2014 was followed?up in 2017 only. Finally, 3 118 older adults aged 65 and older with complete information on albumin, Hs?CRP and body mass index (BMI) were included in this study. Plasma samples of older adults were collected for the detection of albumin and Hs?CRP at baseline survey. Survival status and follow?up time was recorded for all participants. All older adults were divided into 4 groups according to the levels of plasma albumin and Hs?CRP, and Cox proportional hazard models were constructed to assess their influence on the risk of all?cause mortality. Results Among 3 118 older adults included, the prevalence of hypoalbuminemia was 10.1% (316/3 118), and was 22.8% (711/3 118) for elevated Hs?CRP. During 10 132 person?years of follow?up, 1 212 participants died. Participants with hypoalbuminemia had increased risk of all?cause mortality, with an hazard ratio (HR) and 95% confidential interval (CI) of 1.18 (1.01-1.38), compared to participants with normal plasma albuminemia; participants with elevated Hs?CRP had increased risk of all?cause mortality, with an HR (95%CI) of 1.18 (1.04-1.35), compared to participants with normal plasma Hs?CRP. Participants with normal plasma albumin and elevated Hs?CRP, with hypoalbuminemia and normal Hs?CRP, with hypoalbuminemia and elevated Hs?CRP also had increased risk of all?cause mortality when compared to those with normal plasma albumin and normal Hs?CRP, the HR (95%CI) were 1.16 (1.01-1.34), 1.11 (0.91-1.37) and 1.43 (1.11-1.83), respectively. Conclusion Hypoalbuminemia and elevated Hs?CRP were responsible for increased risk of 5?year all?cause mortality among Chinese older adults from 8 longevity areas.

Objective To investigate the feasibility of multiple model parameters of intravoxel incoherent motion (IVIM) in differential diagnosis of cervical carcinoma and its pathological types.Methods IVIM images of 33 patients with cervical cancer (cervical cancer group) and 30 patients with normal cervix (normal group) were retrospectively analyzed.The monoexponential model parameters (ADC-stand),biexponential model parameters (ADC-slow,ADC-fast,f) and stretched-exponential model values (distributed diffusion coefficient [DDC],α) were measured,respectively.Then the parameters were compared among the two groups,as well as among different pathological types and different pathological grades of cervical cancer.The thresholds and diagnostic efficiency of the parameter values were evaluated with ROC curve.Results ADC-stand,ADC-slow,f,DDC and α values of cervical cancer group were lower than those of normal group (all P＜0.05).The area under the ROC curve of ADC-stand,ADC-slow,DDC,f and a values in diagnosis of cervical cancer was 0.93,0.94,0.96,0.94 and 0.93 (all P＜0.05),and the diagnostic thresholds were 1.03 × 10-3 mm2/s,0.99 × 10-3mm2/s,30.50％,1.21 × 10-3 mm2/s and 0.699,respectively.ADC-stand,ADC-slow and DDC values in cervical squamous cell carcinoma patients were lower than those of cervical adenocarcinoma patients (all P＜0.05).The area under the ROC curve of ADC-stand,ADC-slow and DDC values in differential diagnosis of cervical squamous cell carcinoma and cervical adenocarcinoma was 0.98,0.91 and 0.98 (all P＜0.05),the diagnostic thresholds were 1.11 × 10-3 mm2/s,0.81×10-3 mm2/s and 0.98 × 10-3 mm2/s,respectively.There was no significant difference of the parameters among high,moderate,low differentiation of cervical squamous cell carcinoma.Conclusion Multiple model parameters of IVIM can quantitatively reflect the histological features of cervical cancer.