ObjectiveTo analyze the impact of diabetes-related deaths on the probability of premature mortality and life expectancy in Minhang District of Shanghai from 2004 to 2023, and to provide reference data for the optimization of targeted prevention and control strategies. MethodsAll death cases involving diabetes among the registered residents of Minhang District from 2004 to 2023 were collected. The probability of premature mortality and life expectancy was computed using the abridged life table method. The average annual percent change (AAPC) was calculated with Joinpoint 4.9.0.0. The Arriaga decomposition method was employed for statistical analyses of the influence of cause-specific and age-specific mortality related to diabetes on life expectancy. ResultsThe total number of diabetes-related mortality, crude mortality, and standardized mortality for both males and females in Minhang District from 2004 to 2023 exhibited an increasing trend (P<0.001). The primary causes of death among diabetes-related cases were cardiovascular disease (37.68%), diabetes mellitus (31.95%), and malignant tumor (17.80%). From 2004 to 2023, probability of premature mortality to diabetes-related diseases demonstrated a rising trend (P<0.001), contrasting with the declining trend observed in the overall population (P=0.001). Males showed a significant upward trajectory (P<0.001), while females displayed a stable pattern. Among the diseases exerting considerable influence, cardiovascular disease and malignant tumor revealed a marked increase over time (P<0.001), whereas diabetes mellitus maintained a stable trend; both factors negatively impacted the reduction in probability of premature mortality. From 2004 to 2023, diabetes-related mortality reduced life expectancy among residents by an average of 1.22 years (-49.89%), indicating a negative impact; the reduction was 1.41 years in males and 0.90 years in females. The age groups exhibiting greater negative contributions differed by genders, namely males aged 50‒54 years and females aged 70‒74 years. Cardiovascular disease, diabetes mellitus, and malignant tumor contributed significantly to this decline (-0.46 years, -0.42 years, -0.20 years, respectively), with male experiencing higher negative contributions than females. ConclusionIn Minhang District, the rising mortality associated with diabetes-related diseases negatively impact both the reduction of the probability of premature mortality and the increase in life expectancy. This trend is primarily attributed to the rapid escalation of mortality and younger age demographic of male residents, which warrants significant attention. It is recommended that, based on the enhancement of case management, efforts should be directed towards the targeted prevention and control of risk factors and high-risk populations.

OBJECTIVE To provide a reference for improving the relevant standard operating procedures （SOP） and biological sample management in drug clinical trials. METHODS According to Good Clinical Practice， Data On-site Verification Points of Drugs Clinical Trials， Human Genetic Resources Management Regulations Implementation Rules， Qualification Examination Rules of Drug Clinical Trials Institution， based on the experience of managing clinical trials programs， the irregularities in biological samples management were analyzed by using statistical quality control tables and protocol deviation （PD） reported by sponsors， in the context of the quality control of drug clinical trials projects managed by the author from July 2016 to May 2023. The precautions in various aspects of sample management were put forward. RESULTS & CONCLUSIONS A total of 101 biospecimen- related irregularities were found in the 60 drug clinical trials projects. Biological sample collection， preservation， and handling were the aspects with the highest incidence of irregular operations in biological sample management， accounting for 37.62%， 25.74%， and 21.78%， respectively. Regulating the management of biospecimens requires multiple efforts. The institutional office and the ethics committee carefully reviewed the consistency of the protocols， informed consent， and genetic office application involving biospecimen collection and handling when the project was initiated. Institutional office quality controllers should pay attention to the attendance and training of authorized personnel at project initiation. The principal investigator， research nurse， collector， handler， transporter， relevant personnel of the central laboratory， and institutional office quality controller have their roles during the project implementation phase. On this basis， all parties involved in the management of biological samples should do a good job of effective communication， find problems and report them in time， and conduct special studies on key aspects.

OBJECTIVE To investigate the current situation of clinical trial institutions in Chongqing after the recording system of clinical trial institutions, and to put forward suggestions. METHODS A total of 34 clinical trial institutions in Chongqing were selected as the research objects. The research contents mainly included the basic situation of the institutions, staffing, hardware and software construction, project operation and work difficulties, etc. Combined with the research results, suggestions were put forward for the difficulties of the new and old institutions in the operation of clinical trial institutions. RESULTS A total of 29 questionnaires were collected and 29 were valid. The release of clinical trial resources in Chongqing were not sufficient and uniform, there were problems such as insufficient incentive policies, lack of information platform construction, and the number and professional degrees of practitioners need to be improved. The new institutions had certain advantages in project load, office space and willingness to undertake, but it was restricted by principle investigator qualification, project experience and institutional reputation. CONCLUSION It is suggested to clarify the incentive mechanism, enhance the enthusiasm of clinical trials and establish a standardized training mechanism for clinical trial professionals. Make full use of the information platform to improve the efficiency of clinical trials, build a regional information platform to share information and resources, and accelerate the development of regional clinical trials.

Objective:To construct and analyze the visual nomogram predictive model for the prognosis of elderly advanced lung adenocarcinoma patients after surgery based on the Surveillance, Epidemiology, and End Results (SEER) database.Methods:SEER*Stat8.4.0.1 software was used to screen out the data from 17 register in SEER database between 2000 and 2019, and finally 4 453 lung adenocarcinoma patients aged ≥ 65 years who underwent surgical treatment and were diagnosed as stage Ⅲ and Ⅳ according to the 7th edition of the American Joint Committee on Cancer (AJCC) staging criteria were enrolled. The data were randomly divided into the training set (3 117 cases) and the validation set (1 336 cases) in a 7:3 ratio; the epidemilogical data and clinicopathological characteristics of the two groups were compared. LASSO regression was used for data dimensionality reduction to select the best predictors from the prognostic factors of patients. Cox proportional risk model was used to perform univariate and multivariate analyses of the screened variables, and based on R software rms package and the prognostic independent risk factors, the nomogram was constructed to predict the 1-, 3-, and 5-year cancer-specific survival (CSS) rates of the patients. The validation set was validated by using Bootstrap method with 1 000 equal repeated samples with playback, and the accuracy of the nomogram model was verified by using the C-index, receiving operating characteristic (ROC) curves and calibration curves.Results:There were no statistically significant differences in age, gender, race, tumor location, Grade grading, surgery methods, the number of lymph node dissection, radiotherapy, tumor diameter, tumor metastasis, marriage, living condition, TNM staging, radiochemotherapy of training set and validation set (all P > 0.05). In training set, 18 variables were included into LASSO regression analysis and were performed with dimensionality reduction; ultimately, 11 optimal predictive variables were selected, including age ≥ 85 years ( HR = 2.34, 95% CI: 1.803-3.037, P < 0.01), male ( HR = 1.326, 95% CI: 1.228-1.432, P < 0.01), Grade grading Ⅲ-Ⅳ ( HR = 1.333, 95% CI: 0.844-2.105, P < 0.01), undissected lymph nodes ( HR = 2.261, 95% CI: 2.023-2.527, P < 0.01), tumor diameter ≥3.7 cm ( HR = 1.445, 95% CI: 1.333-1.566, P < 0.01), bone metastasis ( HR = 1.535, 95% CI: 1.294-1.819, P < 0.01), brain metastasis ( HR = 1.308, 95% CI: 1.117-1.532, P < 0.01), lung metastasis ( HR = 1.229, 95% CI: 1.056-1.431, P = 0.01), living in rural areas ( HR = 1.215, 95% CI: 1.084-1.363, P < 0.01), TNM staging Ⅳ ( HR = 1.155, 95% CI: 1.044-1.278, P = 0.01), postoperative radiotherapy ( HR = 1.148, 95% CI: 1.054-1.250, P < 0.01); lung adenocarcinoma patients with the above 11 factors had worse prognosis. Based on the variables, the nomogram predictive model was constructed to predict 1-, 3-, and 5-year CSS rates of elderly advanced lung adenocarcinoma patients. Bootstrap method was used for repeated sampling for 1 000 times to verify the modeling effect of nomogram. In the model group, C-index was 0.654 (95% CI: 0.641-0.668), 0.666 (95% CI: 0.646-0.685), respectively in the training set and the validation set. The nomogram was drawn to predict ROC curves of 1-, 3-, and 5-year CSS rates for elderly advanced lung adenocarcinoma patients after operation in the training set and validation set; the area under the curve (AUC) of 1-year, 3-year, and 5-year CSS rates was 0.730 (95% CI: 0.708-0.754) and 0.689 (95% CI: 0.672-0.710), 0.687 (95% CI: 0.668-0.711) and 0.731 (95% CI: 0.697-0.765), 0.712 (95% CI:0.684-0.740) and 0.714 (95% CI: 0.683-0.745), respectively in the training and validation sets. The calibration curve showed a high consistency between the predicted probability of the model and the actual probability. Conclusions:The nomogram model constructed by optimal predictive variables for predicting the prognosis of elderly advanced lung adenocarcinoma patients after surgery may be a convenient tool for survival prediction of these patients.

Background Ozone (O₃) pollution has gradually become a primary problem of air pollution in recent years. Conducting epidemiological studies on the correlation between O₃ concentration variation and risk of cardiovascular and cerebrovascular diseases can provide reference data for O₃ risk assessment and related policy making. Objective To quantitatively evaluate the effects of O₃ exposure on mortalities of cardiovascular and cerebrovascular diseases among residents in Minhang District, Shanghai. Methods Data of mortalities of cardiovascular and cerebrovascular diseases, air pollutants, and meteorological factors in Minhang District of Shanghai from January 1, 2016 to December 31, 2021 were collected. Associations between O₃ concentration and the mortalities due to total cardiovascular and cerebrovascular diseases, coronary heart disease, and stroke were analyzed by generalized additive models with a quasi Poisson distribution with different lag patterns, such as current day effect (lag0), single-day lag effects (lag1-lag3), and cumulative lag effects (lag01-lag03). The subgroup analyses of age, sex, and season were conducted. Furthermore, temperature was divided into low, middle, and high levels based on the 25th percentile (P₂₅) and the 75th percentile (P₇₅) to perform hierarchical analyses. Increased excess risks (ER) of death from target diseases caused by a 10 µg·m⁻³ increase in daily maximum 8 h concentration of O₃ (O₃-8 h) and their 95% confidence intervals (CI) were used to indicate the effects of O₃. Results The associations between O₃ and the risks of death from cardiovascular and cerebrovascular diseases were statistically significant at lag2, lag3, lag02, and lag03 (P<0.05), with the greatest effect size observed at lag03. The ER values of death from cardiovascular and cerebrovascular diseases in general population, male residents, and people aged 65 years and older, from coronary heart disease in male residents, and from stroke in general population increased by 1.02% (95%CI: 0.36%, 1.69%), 1.40% (95%CI: 0.47%, 2.34%), 0.87% (95%CI: 0.19%, 1.55%), 1.96% (95%CI: 0.49%, 3.44%), and 1.02% (95%CI: 0.07%, 1.98%) for a 10 µg·m⁻³ increase in O₃-8 h concentration at lag03, respectively. During the warm season (from April 1 to September 30), the ER values of death from cardiovascular and cerebrovascular diseases and coronary heart disease per 10 µg·m⁻³ increase in O₃ were 1.18% (95%CI: 0.33%, 3.33%) and 2.69% (95%CI: 0.39%, 5.03%), while the O₃ effect was only statistically significant on cardiovascular and cerebrovascular diseases during the cold season (from October 1 to March 31 next year). At the middle and high temperature levels, the ER values of death from cardiovascular and cerebrovascular diseases increased by 1.63% (95%CI: 0.32%, 2.96%) and 1.14% (95%CI: 0.17%, 2.12%) respectively. The two-pollutant models showed similar results after including other pollutants (carbon monoxide, nitrogen dioxide, sulfur dioxide, fine particulate matter, or inhalable particulate matter). Conclusion Ambient O₃ pollution may increase the mortality risks of cardiovascular and cerebrovascular diseases, coronary heart disease, and stroke in Minhang District of Shanghai.

In the context of non-alcoholic fatty liver disease (NAFLD), characterized by dysregulated lipid metabolism in hepatocytes, the quest for safe and effective therapeutics targeting lipid metabolism has gained paramount importance. Sanhuang Xiexin Tang (SXT) and Baihu Tang (BHT) have emerged as prominent candidates for treating metabolic disorders. SXT combined with BHT plus Cangzhu (SBC) has been used clinically for Weihuochisheng obese patients. This retrospective analysis focused on assessing the anti-obesity effects of SBC in Weihuochisheng obese patients. We observed significant reductions in body weight and hepatic lipid content among obese patients following SBC treatment. To gain further insights, we investigated the effects and underlying mechanisms of SBC in HFD-fed mice. The results demonstrated that SBC treatment mitigated body weight gain and hepatic lipid accumulation in HFD-fed mice. Pharmacological network analysis suggested that SBC may affect lipid metabolism, mitochondria, inflammation, and apoptosis-a hypothesis supported by the hepatic transcriptomic analysis in HFD-fed mice treated with SBC. Notably, SBC treatment was associated with enhanced hepatic mitochondrial biogenesis and the inhibition of the c-Jun N-terminal kinase (JNK)/nuclear factor-kappa B (NF-κB) and extracellular signal-regulated kinase (ERK)/NF-κB pathways. In conclusion, SBC treatment alleviates NAFLD in both obese patients and mouse models by improving lipid metabolism, potentially through enhancing mitochondrial biogenesis. These effects, in turn, ameliorate inflammation in hepatocytes.
Humans ; Mice ; Animals ; Non-alcoholic Fatty Liver Disease/metabolism* ; NF-kappa B/metabolism* ; Organelle Biogenesis ; Retrospective Studies ; Mice, Inbred C57BL ; Obesity/metabolism* ; Liver ; Inflammation/metabolism* ; Body Weight ; Lipid Metabolism ; Lipids ; Diet, High-Fat/adverse effects*

OBJECTIVE To investigate the job mo bility of cl inical research coordinators （CRCs） and clinical research associates（CRAs）in Chongqing ，and to explore the feasible methods to improve the job stability of CRCs and CRAs. METHODS Questionnaire survey was conducted to investigate the job mobility of 200 CRCs and CRAs working in 22 drug clinical trial institutions of Chongqing. The contents included basic information ，job mobility ，and reasons for mobility. RESULTS & CONCLUSIONS Totally 178 valid questionnaires were recovered ，with an efficient recovery rate of 89.00％，of which 110 were recovered from CRCs and 68 were recovered from CRAs. Among the surveyed CRCs and CRAs ，the age distribution was mainly 20-30 years old ，accounting for 87.27％ and 82.35％ of the respective population respectively. The overall educational degree of CRAs were slightly higher than those of CRCs. The majors and previous work experience were mainly related to medicine ；the proportion of other non-medicine-related professions who switched to CRCs was higher than that of CRAs. Totally 88.18％ had CRC working experience within 3 years；after having 1-＜3 years of work experience ，50.00％ had worked in 2 or more work units. Totally 64.70％ had CRA working experience within 3 years；after having 1-＜3 years of work experience ，70.37％ had worked in 2 or more work units. CRCs handled 5.38 items of clinical trials and completed 1.22 items on average ；CRAs handled 7.47 items and completes 2.04 items on average. Main reasons of CRCs and CRAs for job-hopping included low salary below expectations，few promotion opportunities ，and too much workload ，accounting for 83.64％/80.88％，45.45％/39.71％，31.82％/ 26.47％，respectively. As an important part of clinical trials ，CRCs and CRAs had high job mobility. It is suggested to establish a unified industry standard ，standardize the management rights and responsibilities of CRCs and CRAs ，optimize the working mode of CRCs and CRAs ，and improve professional identity and sense of belonging ，so as to improve the job stability of relevant

ObjectiveTo analyze the changing trend of cerebrovascular disease burden in Minhang District of Shanghai from 1996 to 2021， and to provide scientific evidence for government to formulate targeted cerebrovascular disease prevention and control strategies. MethodsMortality， years of life lost（YLL）， years of lived with disability（YLD） and disability⁃adjusted life years（DALY） were used to evaluate the burden of cerebrovascular diseases in Minhang District. Joinpoint linear regression was used to analyze the trend of disease burden. ResultsFrom 1996 to 2021， the YLL rate of cerebrovascular diseases in Minhang District showed a downward trend （whole population： APC=-1.69%， t=-6.9， P<0.05）， The YLD rate of cerebrovascular diseases showed a slow upward trend （whole population： APC=1.17%， t=3.5， P<0.05）， The DALY rate of cerebrovascular diseases showed a downward trend， and fluctuated since 2003 （whole population： APC= -1.43%， t=-5.6， P<0.05）. The YLL rate of cerebrovascular diseases in men was higher than that in women， and the YLD rate of cerebrovascular diseases in women was higher than that in men. After 2014， the DALY of cerebrovascular diseases in men was higher than that in women. With the increase of age， the burden of cerebrovascular diseases increased， and the burden of disease increased significantly in the age group above 70. ConclusionThe burden of cerebrovascular diseases in Minhang District is at a high level， and there are differences in age， gender and other aspects. Measures such as screening， intervention and rehabilitation need to be improved to reduce disability and premature death caused by cerebrovascular diseases and to reduce the burden of cerebrovascular diseases on individuals， families and society.

OBJECTIVE To learn the common proto col deviation （PD）in the process of drug clinical trials and discuss the methods and precautions for preventing and reducing PD so as to provide reference for the standardization of drug clinical trials. METHODS According to Good Clinical Practice ，Notice on Issuing Guidelines for Planning and Reporting of Data Management and Statistical Analysis of Drug Clinical Trials ，Guidelines for Ethical Review of Drug Clinical Trials ，ICH E 3，ICH E 6（R2）and other regulations ，the PD reported in the relevant projects managed by the author from March 2017 to February 2022，as well as the PD found in the submission materials and project quality control ，were sorted out and statistically analyzed. RESULTS & CONCLUSIONS A total of 39 drug clinical trials were included ，and 212 subjects were selected. In all projects ，258 PDs were reported，including 28 major PD （accounting for 10.85％）and 230 ordinary PD （accounting for 89.15％）. The report of PD mainly included missed inspections/tests （93 reports，accounting for 36.05％），lack of visits （36 reports，accounting for 13.95％）， inspection/testing out-of-window （29 reports，accounting for 11.24％），dosage and usage of test drugs （28 reports，accounting for 10.85％），drug over-temperature/missing temperature （21 reports，accounting for 8.14％），etc. Avoiding and reducing the occurrence of PD requires the efforts of multiple parties ：the sponsor designs a reasonable protocol with appropriate interview rate and window period after listening to the opinions of multiple parties ；the investigators and clinical research coordinator should strengthen their own learning and training ，and be familiar with the protocol ，Good Clinical Practice and corresponding regulations；the compliance education of the subjects should be strengthened ；the institutional offices and ethics committees should conduct multi-angle and whole-process supervision and management when a drug clinical trial is approved ，in progress ，and jsyj- concluded，to ensure the safety rights and interests of the zdcxX0079） subjects and the quality of clinical trials. On this basis ，all parties should communicate effectively and timely ，report PD in time ，and conduct special studies on major PD that have com occurred and key links that are prone to PD.

OBJECTIVE： To establish the fingerprint of the ethanol e xtract from Melastoma dodecandrum ， to study spectrum-effect relationship of its antioxidant activity. METHODS ：HPLC method and Similarity Evaluation System of TCM Chromatographic Fingerprint （2012 edition）were used to establish the fingerprints of 15 batches of ethanol extracts from M. dodecandrum，and heir similarity was evaluated. The common peaks were identified by comparing with substance control. DPPH free radical scavenging method ，ABTS free radical scavenging method and total antioxidant capacity determination method （FRAP） were used to determine antioxidant activity in vitro of 15 batches of ethanol extracts from M. dodecandrum . Principal component analysis，bivariate correlation analysis and partial least squares regression analysis were used to study the spectrum-effect relationship of the antioxidant activity of the ethanol extracts from M. dodecandrum . RESULTS ：Totally 20 common peaks were identified in HPLC fingerprints of 15 batches of ethanol extracts from M. dodecandrum ；its similarity with the control fingerprint was not less than 0.831；it was identified that peak 3 was gallic acid ，peak 13 was vitexin ，peak 17 was rutin and peak 19 was ellagic acid. The IC 50 values of DPPH radical scavenging method of 15 batches of ethanol extracts from M. dodecandrum were 21.98-57.87 μ g/mL，that of ABTS radical scavenging method were 40.94-101.88 μ g/mL，the results of FRAP method were 0.19-0.48 mg/mL. Principal component analysis showed that the contribution rate of IC 50 variance of DPPH was 80.77％. Bivariate correlation analysis showed that the peak areas of peak 2 （positive correlation ） and peak 11 （negative correlation ） were significantly correlated with antioxidant activity （P＜0.05）；partial least squares regression analysis showed that ，the variable projection importance （VIP）in descending order was peak 11＞peak 2＞peak 16＞peak 15＞peak 12＞peak 13＞peak 18，and their VIP values were greater than 1. Peaks 2，13，15，16 and 18 were positively correlated with antioxidant activity ，and peaks 11 and 12 were negatively correlate d with antioxidant activity ，and the absolute value of standardized regression coefficient were greater than 0.1. CONCLUSIONS ：Fifteen batches of ethanol extracts of M. dodecandrum have antioxidant activity in vitro . The compounds corresponding to common peaks 2，11，12， 13，15，16 and 18 may be the material basis of antioxidant activity of M. dodecandrum .