Objective To compare the difference in risk of drug-induced liver injury(DILI)between Runzao Zhiyang capsules and loratadine tablets.Methods Based on electronic medical records obtained through active drug safety monitoring in China,a retrospective cohort study was conducted to collect clinical data of patients who took oral Runzao Zhiyang capsules or loratadine tablets between January 1,2004,and December 31,2021.After balancing the confounding factors with a 1∶1 propensity score,the logistic regression model was used to analyze the risk of DILI between the two groups.Additionally,the sensitivity analysis of the data before matching and after inverse probability weighting method was conducted.Results A total of 31 636 patients were included,with 26 840 patients taking Runzao Zhiyang capsules orally.After matching there were 4 072 patients in each group,the risk of DILI in the Runzao Zhiyang capsules group was significantly lower than in the loratadine tablets group(0.12％vs.0.83％),OR=0.15(95％CI 0.06 to 0.38).Before matching and after inverse probability weighting,the incidence of DILI in the Runzao Zhiyang capsules group was still lower than that in the loratadine tablets group,and the difference was statistically significant(P＜0.001).Conclusion Runzao Zhiyang capsules have a better safety profile in terms of liver injury compared to the loratadine tablets.The hepatotoxicity of Polygonum multiflorum and its preparations should be scientifically evaluated and rationally treated to ensure medication safety and health.

Objective To assess the association between Metformin use and the risk of dementia in patients with type 2 diabetes mellitus(T2DM).Methods The research data came from the big medical data platform of Yinzhou District,and we constructed a cohort of T2DM patients who had initiated treatment of Metformin or sulfonylurea since January 1,2009.The inverse probability of treatment weighting(IPTW)was used to control the baseline confounding factors,and the Cox regression model was used to estimate the HR(95%CI)of the association between Metformin use and dementia risk.Results The incidence rate of dementia in new users of Metformin(41181 persons)and sulfonylureas(38092 persons)was 128.4 per 100000 person years and 142.3 per 100000 person years respectively.Compared with sulfonylureas,the crude analysis with no adjustment for confounding factors showed that there was a negative association between the use of Metformin and the incidence of dementia,with an HR(95%CI)0.930(0.800～1.090).After adjusting for potential confounders with IPTW,Metformin was not significantly associated with the risk of dementia HR(95%CI)1.040(0.890～1.220).The subgroup analysis results for different baseline characteristics were consistent with the primary analysis results,and there were no statistically significant associations between Metformin and dementia incidence risk in all subgroups.Conclusions There is no significant association between the use of Metformin and the risk of dementia in T2DM patients in the Yinzhou District.

Objective:To construct a risk prediction model for diabetes kidney disease (DKD).Methods:Patients newly diagnosed with type 2 diabetes mellitus (T2DM) between January 1, 2015, and December 31, 2022, were selected as study subjects from the Yinzhou Regional Health Information Platform in Ningbo City. The Lasso method was used to screen the risk factors, and the DKD risk prediction model was established using Cox proportional hazard regression models. Bootstrap 500 resampling was applied for internal validation.Results:The study included 49 706 subjects, with an median ( Q1, Q3) age of 60.00 (50.00, 68.00) years old, and 55% were male. A total of 4 405 subjects eventually developed DKD. Age at first diagnosis of T2DM, BMI, education level, fasting plasma glucose, glycated hemoglobin A1c, urinary albumin, past medical history (hyperuricemia, rheumatic diseases), triglycerides, and estimated glomerular filtration rate were included in the final model. The final model's C-index was 0.653, with an average of 0.654 after Bootstrap correction. The final model's area under the receiver operating characteristic curve for predicting 4-year, 5-year, and 6-year was 0.657, 0.659, and 0.664, respectively. The calibration curve was closely aligned with the ideal curve. Conclusions:This study constructed a DKD risk prediction model for newly diagnosed T2DM patients based on real-world data that is simple, easy to use, and highly practical. It provides a reliable basis for screening high-risk groups for DKD.

Objective:To assess the safety of sitagliptin added to metformin on cardiovascular adverse events in real world patients with type 2 diabetes mellitus(T2DM).Methods:Real world data from Yinzhou Regional Health Care Database were used to select T2DM patients with diagnosis and treatment records in the platform from January 1,2017 to December 31,2022.According to drug prescription records,the patients were divided into metformin plus sitagliptin group(combination group)and metformin monotherapy group(monotherapy group).A series of retrospective cohorts were constructed according to the index date.Finally,full retrospective cohorts were constructed according to propensity score model,including baseline covariates that might be related to outcomes,to match the subjects in the combination group and monotherapy group for the purpose of increasing the comparability of baseline characteristics.The participants were followed up from the index date until the first occurrence of the following events:Diagnosis of outcomes,death,or the end of the study period(December 31,2022).Cox proportional risk model was used to estimate the hazard ratio(HR)and 95％confidence interval(CI)of sitagliptin added to metformin on 3-point major adverse cardiovascular events(3P-MACE)combination outcome and secondary cardiovascular outcomes.Results:Before propensity score matching,the proportion of the pa-tients in combination group using insulin,α glucosidase inhibitors,sodium-glucose transporter 2 inhibi-tors(SGLT-2I)and glienides at baseline was higher than that in monotherapy group,and the baseline fasting blood glucose(FBG)and hemoglobin A1c(HbA1c)levels in combination group were higher than those in monotherapy group.After propensity score matching,5 416 subjects were included in the combination group and the monotherapy group,and baseline characteristics were effectively balanced be-tween the groups.The incidence densities of 3P-MACE were 6.41/100 person years and 6.35/100 per-son years,respectively.Sitagliptin added to metformin did not increase or decrease the risk of 3P-MACE compared with the metformin monotherapy(HR=1.00,95％CI:0.91-1.10).In secondary outcomes analysis,the incidence of cardiovascular death was lower in the combination group than in the monothera-py group(HR=0.59,95％CI:0.41-0.85),and no association was found between sitagliptin and the risk of myocardial infarction and stroke(HR=1.12,95％CI:0.89-1.41;HR=0.99,95％CI:0.91-1.12).Conclusion:In T2DM patients in Yinzhou district of Ningbo,compared with metformin alone,sitagliptin added to metformin may reduce the risk of cardiovascular death,and do not increase the inci-dence of overall cardiovascular events.The results of this study can provide real-world evidence for post-marketing cardiovascular safety evaluation of sitagliptin.

The establishment of a traceability system for the entire industry chain of Chinese medicinal materials can enhance regional brand building,raise the quality awareness of medicinal material producers,standardize the production processes of Chinese medicinal materials,and ensure the production of high-quality medicinal materials.Sichuan Province has successfully implemented a provincial-level Traditional Chinese Medicine(TCM)tracing system that is interconnected across provinces,cities,and counties.This system enables the complete tracking of the entire supply chain,starting from seed and seedling cultivation,through planting and breeding,harvesting and processing,and finally to the production and distribution of decoction pieces in trade and medical institutions.This research provides a comprehensive overview of the progress made in establishing the Chinese herbal medicine traceability system in Sichuan Province.It analyzes the existing challenges faced by participating enterprises,such as the hierarchy of involvement,information integrity,and the overall impact of the system.Moreover,the paper presents valuable insights and suggestions for the further development of the Chinese herbal medicine traceability system in Sichuan Province.These recommendations focus on enhancing the traceability scope,improving service capabilities,promoting data sharing,and establishing standardized norms and guidelines.

This paper briefly introduces the definition, classification and significance of effect modification in epidemiological studies, summarizes the difference between effect modifier and confounders, and analyze the influence as well as the role of effect modification in epidemiological studies and Meta-analysis. In this paper, the possible scenarios of effect modification and related analysis strategy in Meta-analysis are indicated by graphics, aiming to arouse researchers' attention to effect modification. This paper also demonstrates how to identify and deal with effect modification in Meta-analysis through a study case of "Efficacy of sodium-glucose cotransporter 2 inhibitors in patients with type 2 diabetes", and shows the analysis process and interpretation of results of subgroup analysis and Meta-regression methods respectively. The advantages and disadvantages of these two methods are summarized to provide reference for the method selection of future research.

This paper briefly introduces the characteristics, research significance, and global reporting status of effect modification in network Meta-analysis, demonstrates the heterogeneity caused by effect modification in network Meta-analysis, and emphasizes the importance of exploring effect modification in network Meta-analysis. This paper also summarizes the normalized description and analysis strategies of effect modification in network Meta-analysis. Finally, by the case of "comparison of efficacy of three new hypoglycemic drugs in reducing body weight in type 2 diabetes patients", this paper demonstrates the realization of subgroup analysis and network Meta-regression in exploring effect modification, summarizes the advantages and disadvantages of the two methods, to provide references for future researchers.

Objective:Differences between randomized controlled trial (RCT) results and real world study (RWS) results may not represent a true efficacy-effectiveness gap because efficacy-effectiveness gap estimates may be biased when RWS and RCT differ significantly in study design or when there is bias in RWS result estimation. Secondly, when there is an efficacy- effectiveness gap, it should not treat every patient the same way but assess the real-world factors influencing the intervention's effectiveness and identify the subgroup likely to achieve the desired effect.Methods:Six databases (PubMed, Embase, Web of Science, CNKI, Wanfang Data, and VIP) were searched up to 31 st December 2022 with detailed search strategies. A scoping review method was used to integrate and qualitatively describe the included literature inductively. Results:Ten articles were included to discuss how to use the RCT research protocol as a template to develop the corresponding RWS research protocol. Moreover, based on correctly estimating the efficacy-effectiveness gap, evaluate the intervention effect in the patient subgroup to confirm the subgroup that can achieve the expected benefit-risk ratio to bridge the efficacy-effectiveness gap.Conclusion:Using real-world data to simulate key features of randomized controlled clinical trial study design can improve the authenticity and effectiveness of study results and bridge the efficacy-effectiveness gap.

This paper briefly introduces the unique advantages, overall analysis ideas and existing analysis methods of individual patient data Meta-analysis in terms of effect modification. In addition to Meta-regression and subgroup analysis, this paper also introduces the analysis methods based on part of individual patient data integrated with aggregated data and summarizes the current reporting of the above mentioned methods. In addition, the application and results interpretation of the above mentioned methods in individual patient data Meta-analysis are presented in this paper by taking "Effects of sodium-glucose cotransporter 2 inhibitors on SBP in patients with type 2 diabetes" as an example and by introducing their advantages and limitations.

Objective:Randomized controlled trials (RCT) usually have strict implementation criteria. The included subjects' characteristics of the conditions for the intervention implementation are quite different from the actual clinical environment, resulting in discrepancies between the risk-benefit of interventions in actual clinical use and the risk-benefit shown in RCT. Therefore, some methods are needed to enhance the extrapolation of RCT results to evaluate the real effects of drugs in real people and clinical practice settings.Methods:Six databases (PubMed, Embase, Web of Science, CNKI, Wanfang Data, and VIP) were searched up to 31 st December 2022 with detailed search strategies. A scoping review method was used to integrate and qualitatively describe the included literature inductively. Results:A total of 12 articles were included. Three methods in the included literature focused on: ①improving the design of traditional RCT to increase population representation; ②combining RCT Data with real-world data (RWD) for analysis;③calibrating RCT results according to real-world patient characteristics.Conclusions:Improving the design of RCT to enhance the population representation can improve the extrapolation of the results of RCT. Combining RCT data with RWD can give full play to the advantages of data from different sources; the results of the RCT were calibrated against real-world population characteristics so that the effects of interventions in real-world patient populations can be predicted.