Objective: To investigate the impact of disposable plastic food container usage on the executive function among primary school students, so as to provide the evidence for the formulation of relevant health policies. Methods: From November 2023 to May 2024, a convenience sampling method was employed to select 1 118 grade 1-3 students from three primary schools in a central district of Chongqing. A self developed questionnaire was used to collect demographic characteristics and data on disposable plastic food container usage. Executive function of primary school students was assessed using the Childhood Executive Functioning Inventory (CHEXI). Multivariate linear regression analysis was conducted to explore the associations between disposable plastic food container usage and heating with executive function among primary school students. Results: Median scores for working memory, inhibition and total executive function among primary school students were 32 (26, 39), 33 (28, 38), and 66 (54, 75), respectively. Multivariate linear regression analysis showed that among girls, higher frequencies of eating meals from plastic lunchboxes were associated with higher CHEXI working memory scores ( β =1.29), inhibition scores ( β =1.57), and total executive function scores ( β =2.85) ( P <0.05). Compared to girls who did not use plastic cups or drank bottled water, those who used plastic cups for drinking or drank bottled water had higher scores in working memory ( β =2.63), inhibition ( β =2.10), and total executive function ( β =4.73); compared to girls who did not eat canned food from metal cans, those who ate such food had higher scores in working memory ( β =3.62), inhibition ( β =1.89), and total executive function ( β =5.50) ( P <0.05).Among boys, higher frequencies of eating meals from plastic lunchboxes were associated with higher inhibition scores ( β =1.13) ( P <0.05). Compared to girls who ate with a plastic lunch box and did not heat it when they ate,girls who more frequent heating plastic lunchboxes with food inside had higher working memory scores ( β = 5.39), inhibition scores ( β =4.29), and total executive function scores ( β = 9.68) ( P <0.05). Conclusions The use of disposable plastic food containers may adversely affect executive function of primary school students, with a more pronounced effect observed in girls. Strengthened regulation of disposable plastic products and health education are urgently needed.

Mitochondrial dysfunction in chondrocytes is a key pathogenic factor in osteoarthritis (OA), but directly modulating mitochondria in vivo remains a significant challenge. This study is the first to verify a correlation between mitochondrial dysfunction and the downregulation of the FOXO3 gene in the cartilage of OA patients, highlighting the potential for regulating mitophagy via FOXO3 gene modulation to alleviate OA. Consequently, we developed a chondrocyte-targeting CRISPR/Cas9-based FOXO3 gene-editing tool (FoxO3) and integrated it within a nanoengineered 'truck' (NETT, FoxO3-NETT). This was further encapsulated in injectable hydrogel microspheres (FoxO3-NETT@SMs) to harness the antioxidant properties of sodium alginate and the enhanced lubrication of hybrid exosomes. Collectively, these FoxO3-NETT@SMs successfully activate mitophagy and rebalance mitochondrial function in OA chondrocytes through the Foxo3 gene-modulated PINK1/Parkin pathway. As a result, FoxO3-NETT@SMs stimulate chondrocytes proliferation, migration, and ECM production in vitro, and effectively alleviate OA progression in vivo, demonstrating significant potential for clinical applications.

Over the past few decades, tumor immunotherapy has revolutionized the landscape of cancer clinical treatment. There is a flourishing development of combination strategies to improve the anti-tumor efficacy of mono-immunotherapy. However, instead of a straightforward combination of multiple therapeutics, it is more preferable to pursue a synergistic effect by designing rational combinations as well as administration strategies, which are based on a comprehensive understanding of the physiological and pathological features. In this case, the timing and spatial distribution of the combination drugs become essential factors in achieving improved therapeutic outcomes. Therefore, the concept of Sequential Drug Delivery System (SDDS) is proposed to define the spatiotemporally programmed drug delivery/release through triggers of internal conditions and/or external interventions, thus complying with the dynamic disease evolution and the human immunity. This review summarizes the recent advancements in biomaterial-based SDDSs used for spatiotemporally-tuned combination tumor immunotherapy. Furthermore, the rationales behind various engineering strategies are discussed. Finally, an overview of potential synergistic mechanisms as well as their prospects for combination immunotherapy is presented.

Objective:To analyze the epidemiological characteristics and economic burden of palmoplantar pustulosis (PPP) in China.Methods:A population-based retrospective study was conducted using the data from China′s Urban Basic Medical Insurance data from January 1, 2012, to December 31, 2016. International Classification of Diseases code and diagnoses in Chinese for PPP were used to identify cases and estimate the prevalence, incidence, and cost. Subgroup analyses were performed according to age and sex, and sensitivity analyses were conducted to evaluate the robustness of the results. Age-adjusted prevalence rates were calculated based on the 2010 national census data.Results:The crude prevalence and incidence rate of PPP in 2016 were 2.730/100 000 (95% CI: 2.218/100 000-3.242/100 000) and 1.556/100 000 (95% CI: 1.154/100 000-1.958/100 000), and the prevalence rate of females (2.910/100 000) was higher than that of males (2.490/100 000, χ2=97.48, P=0.001). The incidence rate of females (1.745/100 000) was also higher than that of males (1.418/100 000, χ2=85.02, P=0.001). The age peak of incidence and prevalence of patients with PPP was in the 30-39-year age group and a small peak existed in the 0-3-year age group among people under 20 years old. From 2012 to 2016, the average number of visits was (2.44±0.04) per patient, and the total per-capita cost per year was (982.40±39.19) yuan. Conclusion:In 2016, the prevalence and incidence rate of PPP in China were higher in females than in males, and the highest age peak was in the 30-39-year age group.

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.

Objective To systematically assess the interventional effects of aerobic combined resistance exercise on walking ability,cardiorespiratory endurance,dialysis adequacy and quality of life in the patients with hemodialysis(HD).Methods The published randomized controlled trials on the interventional effects of aerobic combined resistance exercise in HD patients were retrieved from the databases of PubMed,Cochrane Library,Embase,Ovid,Web of Science,CNKI,VIP,Wanfang and China Biomedical Literature Service System(SinoMed).The retrieval time was from the database establishment to May 28,2021;the included literatures were analyzed by using RevMan 5.4 software.Results A total of 24 studies with 1 086 research subjects were included.The results showed that compared with the control group(adopting the usual care or conducting no-resistance limb movement),the walking ability,cardiopulmonary endurance and the dimensions of partial quality of life in the HD patients of the intervention group(aerobic combined resistance exercise)were signifi-cantly improved.The dialysis adequacy during dialysis in the intervention group was significantly improved compared with that in the control group.Conclusion Aerobic combined resistance exercise could improve the physical function,quality of life and dialysis adequacy in HD patients,and it is recommended that the patients are encouraged to conduct the aerobic combined resistance exercise by combining with the specific situation.

Objective:To analyze the epidemiological characteristics and economic burden of palmoplantar pustulosis (PPP) in China.Methods:A population-based retrospective study was conducted using the data from China′s Urban Basic Medical Insurance data from January 1, 2012, to December 31, 2016. International Classification of Diseases code and diagnoses in Chinese for PPP were used to identify cases and estimate the prevalence, incidence, and cost. Subgroup analyses were performed according to age and sex, and sensitivity analyses were conducted to evaluate the robustness of the results. Age-adjusted prevalence rates were calculated based on the 2010 national census data.Results:The crude prevalence and incidence rate of PPP in 2016 were 2.730/100 000 (95% CI: 2.218/100 000-3.242/100 000) and 1.556/100 000 (95% CI: 1.154/100 000-1.958/100 000), and the prevalence rate of females (2.910/100 000) was higher than that of males (2.490/100 000, χ2=97.48, P=0.001). The incidence rate of females (1.745/100 000) was also higher than that of males (1.418/100 000, χ2=85.02, P=0.001). The age peak of incidence and prevalence of patients with PPP was in the 30-39-year age group and a small peak existed in the 0-3-year age group among people under 20 years old. From 2012 to 2016, the average number of visits was (2.44±0.04) per patient, and the total per-capita cost per year was (982.40±39.19) yuan. Conclusion:In 2016, the prevalence and incidence rate of PPP in China were higher in females than in males, and the highest age peak was in the 30-39-year age group.

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.