OBJECTIVE To explore whether pachymic acid （Pac） regulates mitochondrial autophagy mediated by the PTEN- induced kinase 1 （PINK1）/Parkin RBR E3 ubiquitin-protein ligase （Parkin） signaling pathway to alleviate myocardial injury in coronary heart disease （CHD） rats. METHODS SD rats were divided into control （Con） group， CHD group， Pac low-dose group （Pac-L group）， Pac high-dose group （Pac-H group）， Pac-H+PINK1/Parkin signaling pathway inhibitor group （Pac-H+3-MA group）， with 10 rats in each group. Except for the Con group， CHD models were established in the remaining groups of rats. After successful modeling， the rats in each group were intraperitoneally injected with the corresponding drugs or normal saline. After continuous intervention for 4 weeks， the left ventricular ejection fraction （LVEF）， left ventricular end-diastolic volume （LVEDV）， left ventricular end-systolic volume （LVESV）， and mean arterial pressure （MAP） of the rats were detected. The levels of creatine kinase isoenzyme （CK-MB）， lactate dehydrogenase （LDH）， cardiac troponin I （cTnI）， and cardiac troponin T （cTnT） in the serum， as well as the levels of tumor necrosis factor-α （TNF-α）， interleukin-10 （IL-10）， IL-1β， reactive oxygen species （ROS）， malondialdehyde （MDA） in the myocardial tissue， and the activities of catalase （CAT） and superoxide dismutase （SOD）， as well as the expression levels of p62， cleaved caspase-3， Parkin， PINK1 proteins and the ratio of microtubule-associated protein 1 light chain 3 Ⅱ （LC3Ⅱ）/LC3Ⅰ ratio were measured. The morphology of myocardial tissue and mitochondrial autophagic vesicles were observed， and the number of mitochondrial autophagic vesicles per unit area and the rate of cardiomyocyte apoptosis were counted. RESULTS Compared with CHD group， LVEF， MAP， IL-10 levels， CAT and SOD activities， p62， Parkin， PINK1 protein expressions， LC3Ⅱ/LC3Ⅰ ratio， the numbers of mitochondrial autophagic vesicles per unit area in the Pac-L and Pac-H E-mail：hzdpft@163.com groups were increased significantly （P＜0.05）； the levels of LVEDV， LVESV， CK-MB， LDH， cTnI， cTnT， TNF-α， IL-1β， ROS and MDA， cell apoptosis rates， and protein expression of cleaved caspase-3 were all decreased significantly （P＜0.05）； and the changes in various indicators were more pronounced in the Pac-H group （P＜0.05）； both groups showed varying degree of improvement in myocardial histopathological morphology. Compared with the Pac-H group， the aforementioned indicators in rats from the Pac-H+3-MA group were all significantly reversed （P＜0.05）. CONCLUSIONS Pac may promote mitochondrial autophagy in cardiomyocytes of CHD rats by activating the PINK1/ Parkin signaling pathway， thereby reducing inflammatory responses and oxidative stress and improving myocardial injury.

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.

This study aims at examining the application and development of digital teaching materials in the field of epidemiology, encompassing both China and international contexts. The research involved conducting search on websites and literature databases to assess the status of digital teaching materials in epidemiology, nationally and internationally. At present, in China, digital teaching materials used in epidemiology are primarily presented in the form of printed books with added QR codes, providing teaching resources such as videos and exercises. However, issues with the level of interactivity have been identified. In foreign countries, with stronger emphasis placed on personalization, interactivity, and the use of rich media technologies in the digital teaching materials, epidemiologically. Enhanced digitization regarding materials and learning outcomes is achieved through features such as real-time notes, interactive animations, and quizzes. These approaches are considered worth considering for adoption. This study provides valuable insights for the digital transformation of epidemiology education.

As a severe clinical manifestation of nonalcoholic fatty liver disease， nonalcoholic steatohepatitis （NASH） is characterized by lipid deposition and inflammatory damage in the liver. At present， clinical medications for NASH are still in the exploratory phase， and it is urgent to make progress. Recent studies have shown that the pathogenesis of NASH is associated with circadian rhythm disorders in the liver， with the specific manifestation of dysregulated expression of liver clock genes such as BMAL1， which increases hepatic lipogenesis， reduces fatty acid oxidation， and activates pro-inflammatory factors. Therefore， improving circadian rhythm of the liver and regulating the expression of liver clock genes are feasible strategies for the prevention and treatment of NASH. Currently， some medications for NASH via activating the proteins encoded by clock genes have been applied in animal experiments， for example， the REVERB full-agonist SR9009 can inhibit the development of liver inflammation， which confirms the possibility of NASH treatment by targeting the proteins encoded by clock genes. This article summarizes the role of hepatic clock genes in regulating lipid metabolism and the development and progression of inflammation in the liver and elaborates on the recent advances in medications targeting clock genes and the proteins encoded by clock genes， in order to provide new targets for the treatment of NASH.

Crisaborole, a phosphodiesterase-4 inhibitor, has been approved for the treatment of mild to moderate atopic dermatitis in China. In addition, crisaborole ointment has been reported for the successful treatment of other inflammatory skin disorders. This review summarizes mechanisms of action of crisaborole and its application to the treatment of atopic dermatitis, psoriasis, vitiligo, seborrheic dermatitis, inflammatory linear verrucous epidermal nevus, lichen simplex chronicus, prurigo pigmentosa, alopecia areata, plasma cell balanitis, and lichen planus.

Objective To conduct bibliometric visualization analyses of the literature domestic and overseas on active surveillance of post-marketing safety of drugs,aiming to display the current status and trend of hotspots in this field and to provide references for future research and the improvement of the Chinese management system of active surveillance.Methods The English and Chinese literature on active surveillance of post-marketing safety of drugs were searched in Web of Science and CNKI respectively and imported into CiteSpace 6.3.R2 software for the analysis of the number of publications,authors,institutions,and national cooperative networks,and the analysis of keyword co-occurrence,clustering and emergence.Results 415 Chinese and 676 English literature were included,with an overall increasing trend in annual publication volume.The author collaboration network of Chinese literature was smaller than that of English literature,and the partnership network was sparse,with no strong centralized institution.Domestic drug regulatory agencies played an important role in the field,while drug companies'monitoring research on their own products was still relatively scarce.The research topic covered active surveillance systems,technical method research,and drug safety active surveillance practice research for specific drugs and diseases.Conclusion Countries worldwide have widely considered active surveillance of post-marketing drug safety.The heat of research activities in China has shown a significant growth trend.However,there is still a significant gap compared with the international frontiers.Further cooperation needs to be strengthened to promote the improvement of the active surveillance management system in China.