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Abstract The impact of O3 on the respiratory system is a significant global problem. Nevertheless, there is insufficient information about its impact on respiratory disorders in northeast China. In this study, we used a generalized additive model (GAM) to determine the correlation between O3 concentrations and respiratory deaths based on the daily meteorological data, pollutant concentrations, and respiratory deaths from 2014 to 2016 in Shenyang, a typical city in northeast China. Single and cumulative lag structures and seasonal modification were considered to investigate the link between O3 exposure and respiratory mortality in Shenyang, northeast China. Synergic effects of O3 and meteorological factors were also evaluated. Results indicated that there was a significant correlation between O3 and the number of deaths caused by respiratory diseases on a daily basis, regardless of the time delay between exposure and the occurrence of the deaths. A 10 µg/m3 rise in O3 concentration was associated with a 0.85% (95% CI 0.18–1.52%) increase in respiratory death at a lag of 1 day and a 1.43% (95% CI 0.40–2.48%) increase at a cumulative lag of 3 days. Stratified analyses revealed that O3 had a greater impact on health under warm conditions compared to cold settings. Additionally, O3 had a more pronounced effect on females than on males. The results for this study could provide some scientific guidance for local environment and health departments.

Abstract Few studies have considered nutrients as a mixture and their impact on Mild Cognitive Impairment (MCI). The generalized linear regression (GLM), weighted quantile sum (WQS) regression, and Bayesian kernel machine regression (BKMR) models are fitted to estimate the association between intake of a mixture of nutrients and MCI. Comparing the results from these three models, vitamin E and vitamin B6 were identified as the most important factors associated with the risk of MCI. Considering the characteristics of BKMR, it may be more advantageous to use BKMR to estimate the combined the joint effects of nutrients mixture. In the future, studies need to move from a “one nutrient at a time” approach to simultaneous analyses of multiple nutrients intakes in order to understand and quantify the joint effect of nutrients mixture on health.

BackgroundDoxorubicin (DOX), a widely employed chemotherapeutic agent in cancer treatment, has seen restricted use in recent years owing to its associated cardiotoxicity. Current reports indicate that doxorubicin-induced cardiotoxicity (DIC) is a complex phenomenon involving various modes of cell death. Astaxanthin (ASX), a natural carotenoid pigment, has garnered significant attention for its numerous health benefits. Recent studies have shown that ASX has a broad and effective cardiovascular protective effect. Our study aims to investigate the protective effects of ASX against DIC and elucidate its underlying mechanisms. This has substantial practical significance for the clinical application of DOX.MethodsBioinformatic analyses were conducted using transcriptomic data from the gene expression omnibus (GEO) database to identify key mechanisms underlying DIC. Network pharmacology was employed to predict the potential pathways and targets through which ASX exerts its effects on DIC. In vitro experiments, following pretreatment with ASX, H9C2 cells were exposed to DOX. Cell viability, injury and the protein expression levels associated with ferroptosis and autophagy were assessed. In the animal experiments, rats underwent 4 weeks of gavage treatment with various doses of ASX, followed by intraperitoneal injections of DOX every 2 days during the final week. Histological, serum, and protein analyses were conducted to evaluate the effects of ASX on DIC.ResultsThe bioinformatics analysis revealed that ferroptosis and autophagy are closely associated with the development of DIC. ASX may exert an anti-DIC effect by modulating ferroptosis and autophagy. The experimental results show that ASX significantly mitigates DOX-induced myocardial tissue damage, inflammatory response, oxidative stress, and damage to H9C2 cells. Mechanistically, ASX markedly ameliorates levels of ferroptosis and autophagy both in vitro and in vivo. Specifically, ASX upregulates solute carrier family 7 member 11 (SLC7A11) and glutathione peroxidase 4 (GPX4), while downregulating the expression of transferrin receptor 1 (TFRC), ferritin heavy chain (FTH1) and ferritin light chain (FTL). Additionally, ASX enhances the expression of P62 and decreases levels of Beclin1 and microtubule-associated proteins light chain 3 (LC3).ConclusionOur results indicate that ferroptosis and autophagy are critical factors influencing the occurrence and progression of DOX-induced cardiotoxicity. ASX can alleviate DIC by inhibiting ferroptosis and autophagy.

IntroductionMacranthoidin B is one of the primary and unique triterpenoid saponin metabolites from Lonicera macranthoides Hand. –Mazz, which is used to treat endometriosis (EMS) in traditional Chinese medicine. However, the effect of macranthoidin B remains unknown in EMS. This study aimed to elucidate the effect and mechanism of macranthoidin B in EMS.MethodsUsing rat autograft EMS model, the volume of ectopic endothelium, the histopathology, serum E2 and PROG were evaluated after macranthoidin B’s treatment. In primary endometriotic stromal and HEC1-B cells, the invasion and metastasis were assessed by scratch wound and Transwell tests. The epithelial-mesenchymal transition and COX-2/PGE2 pathway were examined in vivo and in vitro. Macranthoidin B were combined with LPS or celecoxib.ResultsIn a rat autograft EMS model, macranthoidin B suppressed ectopic lesion volume, improved histopathological morphology, and regulated serum estradiol (E2) and progesterone (PROG) levels. Additionally, macranthoidin B inhibited invasion and metastasis of primary endometriotic stromal cells and HEC1-B cells. Mechanistically, macranthoidin B suppressed COX-2/PGE2 pathway and epithelial-mesenchymal transition both in vivo and in vitro. LPS, the COX-2/PGE2 pathway activator, showed the promotion of epithelial-mesenchymal transition, invasion and metastasis. Macranthoidin B exhibited the antagonistic effects against LPS. Celecoxib, the COX-2/PGE2 pathway inhibitor, restrained the epithelial-mesenchymal transition, invasion and metastasis. This effect of celecoxib was enhanced by macranthoidin B.Discussion Macranthoidin B prevents epithelial-mesenchymal transition through COX-2/PGE2 pathway in EMS. It will facilitate the macranthoidin B’s development and broaden its potential application.

Abstract Background To systematically collect, evaluate, and synthesize evidence from randomized controlled trials (RCTs) supporting the use of electroacupuncture (EA) as an additional treatment option for Vascular mild cognitive impairment (VaMCI), a meta-analysis was carried out. Methods Electronic searches of eight databases were used to locate RCTs that evaluated EA as a VaMCI adjuvant therapy. The Cochrane Risk of bias was used to assess the included trials’ methodological quality. Review Manager 5.4 was used to analyze the data. Trial sequential analysis (TSA) was conducted with the trial sequential analysis program. Results There were 15 RCTs with 1033 subjects in them. Compared to conventional therapy (CT) alone, the Montreal Cognitive Assessment (SMD 0.72, 95 percent CI [0.55, 0.88]), Mini-mental State Examination (SMD 0.73, 95 percent CI [0.60, 0.87]), and activities of daily living (SMD 0.83, 95 percent CI [0.54, 1.12]) were significantly improved while EA was used in conjunction with CT. The current studies exceeded the required information size, according to trial sequential analysis (TSA), demonstrating the reliability of EA adjuvant therapy VaMCI. Conclusions According to the pooled data, EA as an adjunct therapy for the treatment of VaMCI increases clinical efficacy. Although the TSA confirms a stable conclusion, it is encouraged to conduct studies of the highest quality standards.

Abstract Air pollution poses a major threat to both the environment and public health. The air quality index (AQI), aggregate AQI, new health risk–based air quality index (NHAQI), and NHAQI-WHO were employed to quantitatively evaluate the characterization of air pollution and the associated health risk in Gansu Province before (P-I) and after (P-II) COVID-19 pandemic. The results indicated that AQI system undervalued the comprehensive health risk impact of the six criteria pollutants compared with the other three indices. The stringent lockdown measures contributed to a considerable reduction in SO2, CO, PM2.5, NO2 and PM10; these concentrations were 43.4%, 34.6%, 21.4%, 17.4%, and 14.2% lower in P-II than P-I, respectively. But the concentration of O3 had no obvious improvement. The higher sandstorm frequency in P-II led to no significant decrease in the ERtotal and even resulted in an increase in the average ERtotal in cities located in northwestern Gansu from 0.78% in P-I to 1.0% in P-II. The cumulative distribution of NHAQI-based population-weighted exposure revealed that 24% of the total population was still exposed to light pollution in spring during P-II, while the air quality in other three seasons had significant improvements and all people were under healthy air quality level.

IntroductionExposure to fine particulate matter (PM2.5) is known to be associated with cardiovascular diseases. Sesamin (Ses) is a natural phenolic compound found in sesame seeds and sesame oil. Ferroptosis is a novel mode of cell death characterised by iron-dependent lipid peroxidation. This study aims to explore whether PM2.5 can induce ferroptosis in H9C2 cells and to investigate the precise protective mechanism of Ses.MethodsBased on transcriptomic data, PM2.5 may induce ferroptosis in cardiomyocytes. The ferroptosis inducer erastin and ferroptosis inhibitor ferrostatin-1 (Fer-1) were used to illustrate the mechanisms involved in PM2.5-induced H9C2 cell injury. Using network pharmacology, the pharmacological mechanism and potential therapy targets of Ses were explored for the treatment of PM2.5-induced cardiomyocyte injury. H9C2 cells were cultured and pretreated with Fer-1 or different concentrations of Ses, and then cardiomyocyte injury model was established using erastin or PM2.5. Indicators of oxidative responses, including total superoxide dismutase, reduced glutathione, glutathione peroxidase and malondialdehyde, were measured. The expression levels of ferroptosis-related proteins were determined through Western blot analysis.ResultsResults demonstrate that PM2.5 induces ferroptosis in H9C2 cells and Ses exerts a protective effect by suppressing ACSL4-mediated ferroptosis.DiscussionOverall, these findings elucidate a novel mechanism by which Ses ameliorates the detrimental effects of PM2.5 on cardiomyocytes.

Hepatotoxicity is an significant side effect of doxorubicin (DOX), while astaxanthin (ASX) has the anti-liver injury biological functions. In this study, we utilized in vivo and in vitro methods to investigate the protective effect of ASX against DOX-induced hepatotoxicity and elucidate its potential mechanism. Our researchers measured liver injury indicators and the expression of ferroptosis-related protein (transferrin receptor 1 (TFRC), ferroportin 1 (FPN1), ferritin light chain (FTL), ferritin heavy chain-1 (FTH1), glutathione peroxidase 4 (GPX4), and solute carrier family 7 member 11 (SLC7A11)) in rats and HepG2 cells. We found that ASX could effectively reduce ferroptosis level and relieve a range of DOX-caused manifestations of liver injury, including inflammation and oxidative damage. ASX may play the same role as ferroptosis inhibitor, Fer-1 and DFP, in this process. The findings demonstrated that the intervention with ASX ameliorated the DOX-induced liver injury by mitigating the DOX-induced ferroptosis through inhibiting iron accumulation.

Abstract Dengue is a rapidly spreading mosquito‐borne infectious disease that is sensitive to climate factors and poses a major public health concern worldwide. We analyzed dengue incidence trends and the relationship between annual mean minimum temperatures (AMMTs) and dengue incidence rates from 1990 to 2019 in 122 countries using the Global Burden of Disease and TerraClimate data sets. We also projected global dengue incidence rates under different carbon emission scenarios using temperature data from the Coupled Model Intercomparison Project Phase 6 (CMIP6) data set. Our results reveal a significant increase in global dengue cases from 1990 to 2019 and a positive correlation between temperature and dengue incidence. The association between AMMT and dengue incidence strengthened at temperatures exceeding 21°C. Central and eastern sub‐Saharan Africa, as well as Oceania, were identified as the regions most sensitive to dengue; males and individuals aged 15–19 or 70–84 years were the most susceptible to dengue under rising temperatures. Our projections suggest that global dengue incidence will substantially increase by 2050 and 2100. By 2100, regions including Africa, the Arabian Peninsula, the southern United States, southern China, and island countries in the Pacific and Indian Oceans are projected to become year‐round dengue‐endemic under a high‐emission climate scenario. Our findings underscore the importance of implementing effective measures to mitigate the impact of climate change on dengue transmission. Identifying high‐risk areas and susceptible populations, along with understanding the projected expansion of dengue‐endemic regions, will provide valuable guidance for targeted interventions to address this growing global health challenge in the face of changing climatic conditions.

Abstract The prevalence of malnutrition in diabetic patients and its influencing factors remain poorly described. We aim to investigate the prevalence of malnutrition and the influencing factors in diabetic patients through meta‐analysis. Utilizing search terms, such as diabetes, malnutrition, and prevalence, we systematically searched eight databases, including Embase, PubMed, Web of Science, The Cochrane Library, China Knowledge Resource Integrated Database (CNKI), Wanfang Database, Chinese Biomedical Database (CBM), and VIP Database, from inception to May 4, 2023. The search aimed to identify studies related to the prevalence of malnutrition and its influencing factors in adult patients with diabetes. Cohort studies, case–control studies, and cross‐sectional studies that met the inclusion criteria were included in the analysis. Stata 16.0 software was used for meta‐analysis. Quality of the evidence was assessed using Grading of Recommendations, Assessment, Development and Evaluation (GRADE). The study protocol is registered with Prospective Register of Systematic Reviews (PROSPERO), CRD42023443649. A total of 46 studies were included, involving 18 062 patients with ages ranging from 18 to 95 years. The overall malnutrition prevalence was 33% (95% confidence interval [CI]: 0.25–0.40), compared with an at‐risk prevalence of 44% (95% CI: 0.34–0.54). Sixteen factors associated with malnutrition in diabetic patients were identified. This meta‐analysis provides insights into the prevalence of malnutrition and its risk factors in diabetic patients. Regular nutritional screening for patients with risk factors is essential for early detection and intervention.

Background: The effect of dietary antioxidant capacity on health has attracted increasing attention, but unequivocal evidence for its benefits on cardiovascular diseases is still lacking. Objectives: Our aim was to assess the association between composite dietary antioxidant index (CDAI) and Life’s Essential 8 (LE8), an evaluation indicator of cardiovascular health (CVH), in two large cohorts. Methods: The cross-sectional study used data from the National Health and Nutrition Examination Survey (NHANES) 2005–2018 and Community Cohort Study on Specialized Nervous System Diseases (CCSNSD) 2018. The relationship between CDAI and CVH was studied by multinomial logistic regression, restricted cubic spline, subgroup and sensitivity analysis. Results: After adjusting for all potential confounding factors, it suggested that higher CDAI was positively associated with higher CVH (NHANES: OR Q4 vs. Q1 = 0.19, 95 % CI: 0.14–0.25; CCSNSD: OR Q4 vs. Q1 = 0.03, 95 % CI: 0.03–0.04). And a nonlinear dose–response relationship between CDAI and CVH was observed in two large cohorts. The robustness of the results was further demonstrated by sensitivity analysis. Among them, Mendelian randomization analysis showed that higher Vitamin C and Vitamin E intakes were causally associated with a lower risk of CVD. Moreover, there was a stronger positive correlation between the CDAI and CVH among individuals with lower socioeconomic status in both cohorts. Conclusion: Our findings demonstrated the potential benefit of dietary antioxidant intake in improving CVH. Besides, the relationship between CDAI and CVH may be influenced by income levels, highlighting the need for targeted interventions in populations with low income to increase CVH levels.

BackgroundWhile several risk factors for knee osteoarthritis (KOA) have been recognized, the pathogenesis of KOA and the causal relationship between modifiable risk factors and KOA in genetic epidemiology remain unclear. This study aimed to determine the causal relationship between KOA and its risk factors.MethodsData were obtained from published Genome-Wide Association study (GWAS) databases. A two-sample Mendelian randomization (MR) analysis was performed with genetic variants associated with risk factors as instrumental variables and KOA as outcome. First, inverse variance weighting was used as the main MR analysis method, and then a series of sensitivity analyses were conducted to comprehensively evaluate the causal relationship between them.ResultsUnivariate forward MR analysis revealed that genetically predicted hypothyroidism, hyperthyroidism/thyrotoxicosis, educational level, income level, metabolic syndrome (MS), essential hypertension, height, hot drink temperature, diet (abstaining from sugar-sweetened or wheat products), and psychological and psychiatric disorders (stress, depression, and anxiety) were causally associated with KOA. Reverse MR exhibits a causal association between KOA and educational attainment. Multivariate MR analysis adjusted for the inclusion of potential mediators, such as body mass index (BMI), smoking, alcohol consumption, and sex, exhibited some variation in causal effects. However, hyperthyroidism/thyrotoxicosis had a significant causal effect on KOA, and there was good evidence that height, hypothyroidism, educational level, psychological and psychiatric disorders (stress, depression, and anxiety), and abstaining from wheat products had an independent causal relationship. The mediating effect of BMI as a mediator was also identified.ConclusionThis study used MR to validate the causal relationship between KOA and its risk factors, providing new insights for preventing and treating KOA in clinical practice and for developing public health policies.

BackgroundDiminished ovarian reserve (DOR) refers to a decrease in the number or quality of oocytes in the ovarian cortex, which is a degenerative disease of the reproductive system, and can further develop into premature ovarian failure. There are few studies on acupuncture and moxibustion for DOR, which are still in the exploratory stage.Methods/designThis study was a real-world case registry study. According to whether the subjects received conception vessel acupuncture or not, they were divided into the basic treatment combined with conception vessel acupuncture group and the basic treatment group. A total of 1221 patients with DOR were enrolled and treated for 12 weeks. The percentage of patients with ≥30% improvement in anti-Müllerian hormone (AMH) was evaluated at the end of week 12. Secondary outcomes included Antral follicle count (AFC), modified Kupperman scale, basal FSH level, LH level, FSH/LH ratio, positive pregnancy, clinical pregnancy, early spontaneous abortion, ongoing pregnancy, and ectopic pregnancy.DiscussionThis study provides clinical evidence and theoretical support for the treatment of DOR with conception vessel acupuncture and moxibustion, so as to guide and improve the efficacy of acupuncture and moxibustion. Trial registrationAcupuncture-Moxibustion Clinical Trial Registry ChiCTR2400080471. Registered on 30 January 2024.

Abstract Background Complex interactions between the immune system and the brain may affect neural development, survival, and function, with etiological and therapeutic implications for neurodegenerative diseases. However, previous studies investigating the association between immune inflammation and Alzheimer’s disease (AD) have yielded inconsistent results. Methods We applied Mendelian randomization (MR) to examine the causal relationship between immune cell traits and AD risk using genetic variants as instrumental variables. MR is an epidemiological study design based on genetic information that reduces the effects of confounding and reverse causation. We analyzed the causal associations between 731 immune cell traits and AD risk based on publicly available genetic data. Results We observed that 5 immune cell traits conferred protection against AD, while 7 immune cell traits increased the risk of AD. These immune cell traits mainly involved T cell regulation, monocyte activation and B cell differentiation. Our findings suggest that immune regulation may influence the development of AD and provide new insights into potential targets for AD prevention and treatment. We also conducted various sensitivity analyses to test the validity and robustness of our results, which revealed no evidence of pleiotropy or heterogeneity. Conclusion Our research shows that immune regulation is important for AD and provides new information on potential targets for AD prevention and treatment. However, this study has limitations, including the possibility of reverse causality, lack of validation in independent cohorts, and potential confounding by population stratification. Further research is needed to validate and amplify these results and to elucidate the potential mechanisms of the immune cell-AD association.

Background: Microplastics (MPs) are ubiquitous on earth, posing a growing threat to human health. Previous studies have shown that the lung is a primary organ for MPs exposure. Resveratrol (RES) is a common dietary polyphenol that exhibits anti-inflammatory and antioxidant effects. However, whether RES exerts a protective effect against MPs-induced lung damage is still unknown. Methods: The targets of RES were retrieved from five databases. Differentially expressed genes (DEGs) were identified through comprehensive bioinformatic analysis. Multiple algorithms were employed to screen for the core targets. Ultimately, molecular docking analysis and molecular dynamics (MD) simulations were utilized to confirm the binding affinity between RES and the core targets. Results: In total, 1235 DEGs were identified in the transcriptomes. After removing duplicates, a total of 739 RES targets were obtained from five databases, and 66 of these targets intersected with DEGs. The potential core targets (Esr1, Ccl2) were further identified through topological analysis and machine learning. These findings were subsequently verified by molecular docking and MD simulations. Conclusions: This study demonstrated that RES may mitigate lung injury induced by MPs by targeting Esr1 and Ccl2. Our research offers a novel perspective on the prevention and treatment of MPs-induced lung injury.

Background Myocardial ischemia–reperfusion injury (MIRI) refers to severe damage to the ischemic myocardium following the restoration of blood flow, and it is a major complication of reperfusion therapy for myocardial infarction. Notably, drugs such as metoprolol have been utilized to reduce ischemia–reperfusion injury. Tanshinone IIA is a major constituent extracted from Salvia miltiorrhiza Bunge. Recently, tanshinone IIA has been studied extensively in animal models for controlling MIRI. Therefore, we conducted a meta-analysis on the application of tanshinone IIA in rat models with MIRI to evaluate the therapeutic effects of tanshinone IIA. Methods A comprehensive search was conducted across PubMed, Web of Science, Embase, the Cochrane Library, the China National Knowledge Infrastructure database, the Wanfang database, and the Chinese Scientific Journal Database to gather studies on tanshinone IIA intervention in rat models with MIRI.We employed SYRCLE’s risk of bias tool to assess study quality. The primary outcome indicators were superoxide dismutase (SOD) and malondialdehyde (MDA). Myocardial infarction area was a secondary outcome indicator. This study was registered at PROSPERO (registration number CRD 42022344447). Results According to the inclusion and exclusion criteria, 15 eligible studies were selected from 295 initially identified studies. In rat models with MIRI, tanshinone IIA significantly increased SOD levels while reducing MDA levels and myocardial infarction area. Moreover, the duration of myocardial ischemia influenced the effectiveness of tanshinone IIA. However, additional high-quality research studies are needed to establish the efficacy and definitive guidelines for the use of tanshinone IIA. Animal studies demonstrated that tanshinone IIA exerted a significant therapeutic effect when the ischemia duration was less than 40 minutes. Tanshinone IIA was found to be more effective when administered via intravenous, intraperitoneal, and intragastric routes at doses above 5 mg/kg. Additionally, treatment with tanshinone IIA at all stages—prior to myocardial ischemia, after ischemia but before reperfusion, prior to ischemia and after reperfusion, and after reperfusion—showed satisfactory results. Conclusions Tanshinone IIA enhanced SOD activity and reduced MDA levels, thereby ameliorating oxidative stress damage during MIRI. Additionally, it reduced the myocardial infarction area, indicating its effectiveness in mitigating MIRI-induced damage in rats and demonstrating a myocardial protective effect. These findings contribute valuable insights for developing MIRI treatment strategies.

BackgroundDigital health interventions (DHIs) have shown promising results for the management of chronic wounds. However, its effectiveness compared to usual care and whether variability in the type of intervention affects wound outcomes are unclear. ObjectiveThe main objective was to determine the effectiveness of DHIs on wound healing outcomes in adult patients with chronic wounds. The secondary objectives were to assess if there was any variation in wound healing outcomes across the various types of DHIs. MethodsIn total, 9 databases were searched for the literature up to August 1, 2023. Randomized controlled trials (RCTs), cohort studies, and quasi-experimental studies comparing the efficacy of DHIs with controls in improving wound outcomes in adult patients with chronic wounds were included. Study selection, data extraction, and risk of bias assessment were conducted independently by 2 reviewers. We assessed the quality of each RCT, cohort study, and quasi-experimental study separately using the Cochrane risk of bias tool, ROBINS-I, and the Joanna Briggs Institute Critical Appraisal tools checklists. Relative risks (RRs) and 95% CIs were pooled using the random effects model, and heterogeneity was assessed by the I2 statistic. Subgroup analysis and sensitivity analysis were also performed. ResultsA total of 25 studies with 8125 patients were included in this systematic review, while only 20 studies with 6535 patients were included in the meta-analysis. Efficacy outcomes in RCTs showed no significant differences between the DHIs and control groups in terms of wound healing (RR 1.02, 95% CI 0.93-1.12; P=.67) and all-cause mortality around 1 year (RR 1.08, 95% CI 0.55-2.12; P=.83). Compared with the control group, the use of DHIs was associated with significant changes in adverse events (RR 0.44, 95% CI 0.22-0.89; P=.02). Subgroup analysis suggested a positive effect of the digital platforms in improving wound healing (RR 2.19, 95% CI 1.35-3.56; P=.002). Although meta-analysis was not possible in terms of wound size, cost analysis, patient satisfaction, and wound reporting rates, most studies still demonstrated that DHIs were not inferior to usual care in managing chronic wounds. ConclusionsThe findings of our study demonstrate the viability of adopting DHIs to manage chronic wounds. However, more prominent, high-quality RCTs are needed to strengthen the evidence, and more detailed clinical efficacy research is required. Trial RegistrationPROSPERO CRD42023392415; https://tinyurl.com/4ybz6bs9

Abstract Background Long-term exposure of humans to air pollution is associated with an increasing risk of cardiovascular diseases (CVDs). Astaxanthin (AST), a naturally occurring red carotenoid pigment, was proved to have multiple health benefits. However, whether or not AST also exerts a protective effect on fine particulate matter (PM2.5)-induced cardiomyocyte damage and its underlying mechanisms remain unclear. Methods In vitro experiments, the H9C2 cells were subjected to pretreatment with varying concentrations of AST, and then cardiomyocyte injury model induced by PM2.5 was established. The cell viability and the ferroptosis-related proteins expression were measured in different groups. In vivo experiments, the rats were pretreated with different concentrations of AST for 21 days. Subsequently, a rat model of myocardial PM2.5 injury was established by intratracheal instillation every other day for 1 week. The effects of AST on myocardial tissue injury caused by PM2.5 indicating by histological, serum, and protein analyses were examined. Results AST significantly ameliorated PM2.5-induced myocardial tissue injury, inflammatory cell infiltration, the release of inflammatory factors, and cardiomyocyte H9C2 cell damage. Mechanistically, AST pretreatment increased the expression of SLC7A11, GPX4 and down-regulated the expression of TfR1, FTL and FTH1 in vitro and in vivo. Conclusions Our study suggest that ferroptosis plays a significant role in the pathogenesis of cardiomyocyte injury induced by PM2.5. AST may serve as a potential therapeutic agent for mitigating cardiomyocyte injury caused by PM2.5 through the inhibition of ferroptosis.

Abstract Ambient pollutants, particularly fine particulate matter (PM2.5) and ozone (O3), pose significant risks to both public health and economic development. In recent years, PM2.5 concentration in China has decreased significantly, whereas that of O3 has increased rapidly, leading to considerable health risks. In this study, a generalized additive model was employed to establish the relationship of PM2.5 and O3 exposure with non-accidental mortality across 17 districts and counties in Jilin Province, China, over 2015–2016. The health burden and economic losses attributable to PM2.5 and O3 were assessed using high-resolution satellite and population data. According to the results, per 10 µg/m3 increase in PM2.5 and O3 concentrations related to an overall relative risk (95% confidence interval) of 1.004 (1.001–1.007) and 1.009 (1.005–1.012), respectively. In general, the spatial distribution of mortality and economic losses was uneven. Throughout the study period, a total of 23,051.274 mortalities and 27,825.015 million Chinese Yuan (CNY) in economic losses were attributed to O3 exposure, which considerably surpassing the 5,450.716 mortalities and 6,553,780 million CNY in economic losses attributed to PM2.5 exposure. The O3-related health risks and economic losses increased by 3.75% and 9.3% from 2015 to 2016, while those linked to PM2.5 decreased by 23.33% and 18.7%. Sensitivity analysis results indicated that changes in pollutant concentrations were the major factors affecting mortality rather than baseline mortality and population.

Teachers have come under significant scrutiny due to their pivotal role in educational context and lately, the study of emotion-connected aspects in teachers' education domain has got much attention and experts in this domain proved that emotion is at the center of teaching subjects. Also as teaching is an emotionally challenging occupation, it often results in high levels of stress and consequently burnout which has become a prominent concern in mainstream education in recent years. As the main issue of education, teachers' emotions should be taken into account as their positive emotions and their regulation have been highlighted in the literature. Therefore, the study underscores the critical significance of Chinese English as a foreign language (EFL) teachers' well-being and emotion regulation and their relations to burnout. To fulfill the research objectives, 398 English teachers participated in the assessment of the studied concepts. The findings, analyzed through Structural Equation Modeling (SEM), reveal that both variables significantly contribute to the reduction of job burnout in teachers. This study discusses key findings, implications, and limitations while also offering suggestions for future research directions.

ObjectivesHypertension and hypertensive disorders of pregnancy (HDP) are common diseases in women at different stages, which affect women’s physical and mental health, and the impact of the latter on the offspring cannot not be ignored. Observational studies have investigated the correlation between uterine leiomyoma (UL) and the above conditions, but the relationship remains unclear. In this study, we employed two-sample Mendelian randomization (MR) analysis to assess the association between UL and hypertension, HDP, as well as blood pressure.MethodsWe collected genetic association data of UL (35,474 cases), hypertension (129,909 cases), HDP (gestational hypertension with 8,502 cases, pre-eclampsia with 6,663 cases and eclampsia with 452cases), systolic blood pressure (SBP) and diastolic blood pressure (DBP) (both 757,601 participants) from published available genome-wide association studies (GWAS). The single nucleotide polymorphisms (SNPs) associated with UL phenotype were used as instrumental variables, and hypertension, three sub-types of HDP, SBP and DBP were used as outcomes. The inverse-variance weighted (IVW) method was employed as the primary method of causal inference. Heterogeneity was assessed using Cochran’s Q test, and sensitivity analyses were conducted using MR-Egger regression and MR pleiotropy residual sum and outlier (MR-PRESSO) tests to evaluate the pleiotropy of instrumental variables. PhenoScanner search was used to remove confounding SNP. Robustness and reliability of the results were assessed using methods such as the weighted median and weighted mode.ResultsThe IVW analysis revealed a positive correlation between genetically predicted UL and SBP [odds ratio (OR)= 1.67, 95% confidence interval (CI):1.24~2.25, P = 0.0007], and no statistical association was found between UL and hypertension, HDP, or DBP. The MR-Egger regression suggested that the above causal relationships were not affected by horizontal pleiotropy. The weighted median method and weighted model produced similar results to the IVW.ConclusionBased on large-scale population GWAS data, our MR analysis suggested a causal relationship between UL and SBP. Therefore, women with UL, especially pregnant women, should pay attention to monitoring their blood pressure levels. For patients with hypertension who already have UL, interventions for UL may serve as potential therapeutic methods for managing blood pressure.

Skin pigmentation typically arises from the excessive secretion and accumulation of melanin, resulting in a darker complexion compared to normal skin. Currently, the local application of chemical drugs is a first-line strategy for pigmentation disorders, but the safety and efficacy of drugs still cannot meet clinical treatment needs. For long-term and safe medication, researchers have paid attention to natural products with higher biocompatibility. This article begins by examining the pathogenesis and treatment approaches of skin pigmentation diseases and summarizes the research progress and mechanism of natural products with lightening or whitening effects that are clinically common or experimentally proven. Moreover, we outline the novel formulations of natural products in treating pigmentation disorders, including liposomes, nanoparticles, microemulsions, microneedles, and tocosomes. Finally, the pharmacodynamic evaluation methods in the study of pigmentation disorder were first systematically analyzed. In brief, this review aims to collect natural products for skin pigmentation treatment and investigate their formulation design and efficacy evaluation to provide insights for the development of new products for this complex skin disease.

ABSTRACTTo evaluate the effect of exosomes secreted by berberine-treated bone marrow-derived mesenchymal stem cells (BMSCs) on synovial inflammation in collagen-induced arthritis (CIA) model. Exosomes were isolated from berberine-treated BMSCs (Ber-BMSC-EXs) and untreated BMSCs (BMSC-EXs). CIA rats were developed and treated with Ber-BMSC-EXs or BMSC-EXs. Clinical arthritis index was measured, activation of fibroblast-like synoviocytes (FLSs) were evaluated, and response and frequency of T helper 17 (Th17) and regulatory T (Treg) cells as well as cytokine levels in synovial fluid were determined. Ber-BMSC-EXs (with a superior effect than BMSC-EXs) significantly alleviated RA clinical score and paw inflammation, balanced Th17 and Treg cells’ responses and population, modulated levels of pro-inflammatory and anti-inflammatory cytokines in joint synovial fluid, and inhibited FLS activation in CIA rats. Ber-BMSC-EXs (with a significantly greater effect than BMSC-EXs) could significantly ameliorate synovial joint inflammation and clinical symptoms of arthritis in CIA rats, showing that berberine can reinforce anti-arthritic effects of BMSC-EXs.

BackgroundWith the intensification of global climate warming, extreme low temperature events such as cold spells have become an increasingly significant threat to public health. Few studies have examined the relationship between cold spells and mortality in multiple Chinese provinces.MethodsWe employed health impact functions for temperature and mortality to quantify the health risks of the first winter cold spell in China on November 26th, 2022, and analyzed the reasons for the stronger development of the cold spell in terms of the circulation field.ResultsThis cold spell was a result of the continuous reinforcement of the blocking high-pressure system in the Ural Mountains, leading to the deepening of the cold vortex in front of it. Temperature changes associated with the movement of cold fronts produced additional mortality risks and mortality burdens. In general, the average excess risk (ER) of death during the cold spell in China was 2.75%, with a total cumulative excess of 369,056 deaths. The health risks associated with temperatures were unevenly distributed spatially in China, with the ER values ranging from a minimum of 0.14% to a maximum of 5.72%, and temperature drops disproportionately affect southern regions of China more than northern regions. The cumulative excess deaths exibited the highest in eastern and central China, with 87,655 and 80,230 respectively, and the lowest in northwest China with 27,474 deaths. Among the provinces, excess deaths pronounced the highest in Shandong with 29,492 and the lowest in Tibet with only 196.ConclusionThe study can provide some insight into the mortality burden of cold spells in China, while emphasising the importance of understanding the complex relationship between extreme low temperature events and human health. The outcomes could provide valuable revelations for informing pertinent public health policies.

Prevalence of kidney stones has increased continously over several decades worldwide, the major causes of which are largely unknown. To explore the dietary causes of kidney stones, and reveal mechanisms underlying dietary risk factors inducing kidney stones, animal experiments using mice as the disease model were performed. Eight-week old male CD-1 mice were treated by ethylene glycol, cholesterol or/and apple tannins for 3 d, respectively. In the present study, the crystalline analysis in urine and kidney tissues, HE staining kidney sections as well as observation of micro-stones, tannins and cholesterol deposition in kidneys of mice in different groups were conducted. We found that gavage with ethylene glycol, cholesterol and tannins resulted in mice urine solute supersaturation in renal tubules and forming kidney stones. Significant cholesterol and tannin deposits in mouse kidney were observed by laser confocal microscopy and crystals were shown either adhered with or co-deposited with cholesterol and tannin deposits. The primary crystals were found in renal cortex, medullar, especially papilla in the kidney sections under polarized microscope. These findings demonstrate that interaction of cholesterol and tannins in kidney plays a critical role in the formation of kidney stones.

Abstract Introduction Epidural analgesia (EA) is the most widely used intervention for the reduction of labor pain; however, it is contra-indicated for patients with spinal deformity or allergy to anesthetics and may be refused by parturients. As a noninvasive and nonnarcotic analgesic intervention, transcutaneous electrical acupoint stimulation (TEAS) has gained increasing attention in recent years. Therefore, we performed a network meta-analysis to compare the efficacy and safety of TEAS and EA as measured by visual analog scale score, the failure rate of natural delivery, adverse events, and Apgar scores. Methods Relevant randomized controlled trials (RCTs) from four electronic databases (PubMed, EMBASE, Web of Science, and Cochrane CENTRAL) and clinical trials.gov were searched from inception until September 4, 2022. A random effects model was used during analysis, and outcomes were evaluated as standard mean difference (SMD), odds ratio (OR), and 95% confidence intervals (CrI) using STATA (version SE15.0), R (version 3.6.1), and ADDIS (version 1.16.8) software. Results Ten RCTs comprising 1214 parturients were identified by screening. Six RCTs compared TEAS and controls, three compared EA and controls, and one compared TEAS and EA. No heterogeneity was found within the four outcomes. There was no significant difference in any outcomes between interventions or control treatments in terms of SMD, OR, and CrI. Combined with the highest surface under the cumulative ranking curve score, TEAS demonstrated possible better effects in the aspects of analgesic efficacy and safety under certain circumstances. Conclusions TEAS may be a potential alternative for parturients as a simple, noninvasive, and non-pharmacological intervention compared with EA in terms of analgesic efficacy and safety for mothers and neonates.

COVID-19, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a major public health threat. Edible plants are rich in bioactive components, with a variety of functions, such as enhancing immunity, antiviral, anti-inflammatory and so on. Thus, the intake of edible plants to boost the body's resistance to COVID-19 is a promising and possibly affordable strategy. This review revisits the effects of functional components from edible plants (such as polyphenols, polysaccharides, lectin, alkaloids, polyunsaturated fatty acids, terpenoids, and saponins) on COVID-19. The inhibitory effects of bioactive components on the virus's entrance and replication, anti-inflammatory and immune enhancement are discussed. And finally, we present the prospects of using edible plant functional ingredients as vaccine adjuvants and the prospects and problems in the use of edible plant functional components for the prevention of COVID-19. Functional components of edible plants interacted with structural proteins of SARS-CoV-2 virus and key enzymes in virus recognition and replication, thereby inhibiting virus entry and replication in the host. Meanwhile, these bioactive components had anti-inflammatory effects and could inhibit cytokine storms. Therefore, we believe that functional components from edible plants can enhance human resistance to COVID-19 and can be applied in the development of new therapies.

Abstract Emission sources and meteorological conditions are key factors affecting the intensity and duration of air pollution events. In the current study, using the daily concentrations of PM2.5 (particulate matter with a diameter ≤ 2.5 μm) and the water-soluble ions thereof in Lanzhou from March 1, 2021, to May 31, 2021, we investigated the contributions of emission sources and locations of potential sources through positive matrix factorization and potential source contribution function analysis. In addition, synoptic weather patterns affecting pollution were typed using T-model principal component analysis. The results revealed that the average concentrations of PM2.5 for the entire spring, dust storm days, and normal days were 54.3, 158.1 and 33.0 μg/m3, respectively. During dust storm days, sulfate produced from primary emissions was mainly present in the form of K2SO4, Na2SO4, MgSO4, and CaSO4, and nitrate was mainly produced through secondary conversion and took the form of NH4NO3. Dust, industrial entities, biomass combustion, metal smelting, secondary aerosol, and sea salt contributed to 32.0, 29.8, 13.4, 11.2, 10.8 and 2.7% of the spring PM2.5, respectively, in Lanzhou. The main potential sources of PM2.5 during the normal days were in the western parts of Lanzhou. Dust storms entered Lanzhou through the Hexi Corridor from several dust sources: southeastern Kazakhstan, Mongolia, the Kurbantungut Desert, and the Badain Jaran Desert. The northwest high-pressure; northern strong high-pressure and southwest low-pressure; northwest high-pressure and southwest high-pressure synoptic weather circulation types were prone to dust storms. Our results may provide a basis for local environmental governance.

Diabetic vascular complications can affect both microvascular and macrovascular. Diabetic microvascular complications, such as diabetic nephropathy, diabetic retinopathy, diabetic neuropathy, and diabetic cardiomyopathy, are believed to be caused by oxidative stress. The Nox family of NADPH oxidases is a significant source of reactive oxygen species and plays a crucial role in regulating redox signaling, particularly in response to high glucose and diabetes mellitus. This review aims to provide an overview of the current knowledge about the role of Nox4 and its regulatory mechanisms in diabetic microangiopathies. Especially, the latest novel advances in the upregulation of Nox4 that aggravate various cell types within diabetic kidney disease will be highlighted. Interestingly, this review also presents the mechanisms by which Nox4 regulates diabetic microangiopathy from novel perspectives such as epigenetics. Besides, we emphasize Nox4 as a therapeutic target for treating microvascular complications of diabetes and summarize drugs, inhibitors, and dietary components targeting Nox4 as important therapeutic measures in preventing and treating diabetic microangiopathy. Additionally, this review also sums up the evidence related to Nox4 and diabetic macroangiopathy.

Abstract Background Studies have shown that a direct association exists between the diet and blood uric acid concentrations. However, works on the association of dietary patterns with blood uric acid concentrations and hyperuricemia remain limited. Objective This study aims to evaluate the association of dietary patterns with blood uric acid concentrations and hyperuricemia. Methods The relationship between dietary patterns and hyperuricemia was explored through a nutritional epidemiological survey in China (n = 4855). Three statistical methods, including principal component analysis, reduced rank regression (RRR), and partial least squares regression, were used to extract dietary patterns. General linear regression and logistic regression analyses were utilized to explore the relationship of dietary patterns with blood uric acid concentrations and hyperuricemia. Results After adjusting for potential confounding factors, the score for the plant-based dietary pattern was found to be negatively correlated with blood uric acid levels (β = − 3.225) and that for the animal dietary pattern was discovered to be directly correlated with blood uric acid levels (β = 3.645). The participants in the highest quartile of plant-based dietary pattern scores were at a low risk of hyperuricemia (OR = 0.699; 95% CI: 0.561–0.870, P

Abstract Background Immune checkpoint blockade (ICB)-based cancer immunotherapy presents promising efficacy in cancer treatment. However, only a small portion of patients show responsiveness to the treatment, which is partially caused by limited tumor infiltration of T cells. Chemokines CXCL9, CXCL10 and CXCL11 bind to their receptor CXCR3 to regulate T cell invasion. Methods We delivered plasmids encoding CXCL9, CXCL10 and CXCL11 to tumor cells and tumor tissues using nanoparticles and investigated their effect on T cell invasion and infiltration. In addition, we applied these nanoparticles together with anti-PD-1 antibody, which is known to activate T cells and restore immune function against tumor cells. The anti-tumor effects were evaluated. Results Delivering plasmids encoding CXCL9, CXCL10 and CXCL11 by nanoparticles resulted in expression of these chemokines in both LLC cells and tumors. Expressing CXCL9, CXCL10 and CXCL11 promoted the infiltration of T cells in vitro and in vivo, as well as decreased the tumor size. Nanoparticles together with anti-PD-1 displayed the best anti-tumor effects. Conclusions Delivery of CXCL9/10/11 plasmids by nanoparticles promoted T cell infiltration in tumors and synergizes with the activity of anti-PD1 antibody.

Abstract Background Recurrent implantation failure (RIF) in the majority of patients undergoing in vitro fertilization and embryo transfer (IVF-ET) is caused by various factors such as maternal age, embryo quality, endometrial receptivity (ER), and immunity. The incidence of RIF is usually between 5 and 10%. Previous studies have shown that herb-partitioned moxibustion on the navel is one of the treatment methods of acupuncture with a positive effect on pregnancy. However, its application in the treatment of RIF has not been reported. Therefore, this study aims to evaluate the effectiveness and safeness of herb-partitioned moxibustion on the navel in improving the outcome of frozen embryo transfer (FET) in patients with RIF. Methods This study conducts a randomized controlled trial (RCT). It is planned to recruit 210 patients undergoing RIF for FET from Affiliated Hospital of Shandong University of Traditional Chinese Medicine and randomly divide them into the treatment group and the control group in a ratio of 1:1. The patient of the treatment group will be treated with herb-partitioned moxibustion on the navel once a week for three consecutive menstrual cycles. No intervention will be used in the control group for 3 menstrual cycles. In the fourth menstrual cycle, all patients will undergo artificial cycle to prepare the endometrium for FET. The pregnancy outcomes will be recorded after a 3-month follow-up. Primary outcome will be assessed as the ongoing pregnancy rate compared with the control group. Secondary outcomes include the endometrial type, resistance index (RI), pulsatility index (PI) of the bilateral uterine artery, endometrial blood flow, serum estradiol (E2), progesterone (P), biochemical pregnancy rate, implantation rate, and clinical pregnancy rate. Discussion If the results show that the herb-partitioned moxibustion on the navel can improve IVF-ET outcomes in patients with RIF, it will be recommended in clinical practice. Trial registration Chinese Clinical Trial Registry (ChiCTR) ChiCTR2100043954 . Registered on 8 July 2021.

Abstract Background Sedentary behaviours (SBs) are now considered a risk factor for depression. Older adults are sedentary most of the time and are at a high risk of depression. However, not all types of SBs have adverse effects on mental health. Passive SBs (such as watching TV) increase the risk of depression, whereas mentally active SBs (such as using the internet and reading) decrease the risk of depression. The aim of this study was to explore the associations between type of SBs (i.e., passive and mentally active SBs) and depression among people aged 60 years and older in the Hebei Province of China. Methods This cross-sectional study used data from the baseline survey of the Community-based Cohort Study on Nervous System Diseases. A total of 2679 older adults aged ≥60 years from the Hebei Province of China were included in this study. The type and time spent on SBs were self-reported. Watching TV was defined as a passive SB, whereas internet use, reading, and social SBs (including communicating with others and playing chess) were defined as mentally active SBs. Depression was evaluated using the Geriatric Depression Scale. The maximal possible score was 30 points, and ≥ 11 points indicated depression. Logistic regression analysis was used to assess the relationship between SBs and depression. Covariates included sex, age, education, employment, smoking, alcohol consumption, sleep duration, domestic work, physical exercise, body mass index (BMI), and chronic diseases. Results At baseline, the participants who spent two or more hours and 0 h on passive SBs (i.e., TV viewing) had a greater risk of depression (=0 h: adjusted OR = 2.09, 95% CI = 1.18–3.76; 2–3 h: OR = 2.21, 95% CI = 1.16–4.16; > 3 h: OR = 3.59, 95% CI = 1.93–6.68) than the participants who spent 1–2 h on passive SBs. The participants who spent > 1 h on mentally active SBs had a lower risk of depression (adjusted OR = 0.26, 95% CI = 0.06–0.71) than the participants who did not engage in mentally active SBs. Not all mentally active SBs were linked to depression. The participants who engaged in social SBs had a lower risk of depression (adjusted OR: 0.24, 95% CI: 0.06–0.66) than the participants who did not engage in social SBs. Conclusions Spending 2 h or more per day on passive SBs (watching TV) was associated with a high risk of depression among people aged 60 years and older in the Hebei Province of China. Mentally active SBs (predominantly social SBs) could reduce the risk of depression. Some participants with depression probably did not watch TV. These findings suggested that spending more time on social SBs (such as communicating with others and playing chess) rather than watching TV may have important public health implications for preventing and managing depression among older Chinese adults. Moreover, society should attend to the mental health of elderly adults who do not watch TV as they may be more prone to suffer from depressive symptoms.

Abstract Aim Pressure injuries are common adverse events in clinical practice, affecting the well‐being of patients and causing considerable financial burden to healthcare systems. It is therefore essential to use reliable assessment tools to identify pressure injuries for early prevention. The Braden Scale is a widely used tool to assess pressure injury risk, but the literature is currently lacking in determining its accuracy. This study aimed to evaluate the accuracy of the Braden Scale in assessing pressure injury risk. Design Systematic review and meta‐analysis. Methods Articles published between 1973–2020 from periodicals indexed in the PubMed, EMBASE, CINAHL, Web of Science and the Cochrane Library were selected. Two reviewers independently selected the relevant studies for inclusion. Data were analysed by the STATA 15.0 and the RevMan 5.3 software. Results In total, 60 studies involving 49,326 individuals were eligible for this meta‐analysis. The pooled SEN, SPE, PLR, NLR, DOR and AUC were 0.78 (95% CI: 0.74 to 0.82), 0.72 (95% CI: 0.66 to 0.78), 2.80 (95% CI: 2.30 to 3.50), 0.30 (95% CI: 0.26 to 0.35), 9.00 (95% CI: 7.00 to 13.00) and 0.82 (95% CI: 0.79 to 0.85), respectively. Subgroup analyses indicated that the AUC was higher for prospective design (0.84, 95% CI: 0.81 to 0.87), mean age

Given the bond between emotion and cognition underlying the broaden-and-build theory of positive emotions, positive and negative emotions have critical roles in cognitive skills. The aim of this review was to probe into the triarchic relationship between L2 learners’ cognition, emotion, and language performance, reflected in the bond between self-efficacy, foreign language anxiety, and speaking skill, in light of the main emerging theories in the field of SLA underpinning this relationship. Moreover, the theoretical foundations, such as learners’ cognitive performances, Bandura’s self-efficacy theory, control-value theory, and positive psychology theory, were explicated in order to justify the relationship between self-efficacy and oral communication skill. Furthermore, the underlying theories such as attentional control theory, complex dynamic system theory, affective filter theory, and cultural schema theory, which relate foreign language anxiety to speaking skill were scrutinized in this review. The review also expounded on the implications and future directions for EFL teachers, material designers, teacher educators, educational policy-makers, and advisors. The ideas can improve their awareness of learner self-efficacy, foreign language anxiety, and oral communication skill in educational contexts.

Abstract Particulate matter (PM) has been proved to be a risk factor for the development of circulatory system diseases (CSDs) around the world. In this study, we collected daily air pollutants, emergency room (ER) visits for CSDs, and meteorological data from 2009 to 2012 in Beijing, China. After controlling for the long-term trend and eliminating the influence of confounding factors, the generalized additive model (GAM) was used to evaluate the short-term effects of PM10 on CSDs and cause-specific diseases. The results showed that for every 10 μg/m3 increase in PM10, the largest effect estimates in ER visits of total CSDs, arrhythmia, cerebrovascular diseases, high blood pressure, ischemic heart disease and other related diseases were 0.14% (95% CI: 0.06–0.23%), 0.37% (95% CI: − 0.23 to 0.97%), 0.20% (95% CI: 0.00–0.40%), 0.15% (95% CI: 0.02–0.27%), 0.18% (95% CI: 0.02–0.35%) and 0.35% (95% CI: − 0.04 to 0.79%), respectively. When NO2 or SO2 was added into the model, the effect estimates of PM10 were mostly attenuated, while in those models with PM2.5 added, the effect estimates of PM10 were mostly increased. Stratified analysis indicated that PM10 had a greater effect on males and the elderly.

Scaffolding is widely used in online learning; however, it is unclear whether scaffolding can effectively enhance students’ online learning performance. To evaluate its effectiveness, we conducted a meta-analysis that included 83 effects sizes from 32 articles published between 2011 and 2021. The findings demonstrated that scaffolding had a significant role in improving students’ online learning performance with an overall effect size of 0.53. In addition, we analyzed the effects of five moderator variables to gain insights into how scaffolding affects students’ online learning performance under different conditions. The discipline, learning outcome type, and scaffolding type were identified as significant moderators. It is expected that the research results will guide teachers to design online scaffolding strategies and improve students’ online learning performance.

Poor transdermal permeability limits the possibility of most drug delivery through the skin. Auxiliary permeable microneedles (AP-MNs) with a three-dimensional network structure can effectively break the skin stratum corneum barrier and assist in the transdermal delivery of active ingredients. Herein, we propose a simple method for preparing AP-MNs using polyvinyl alcohol and Eudragit NM30D for the first time. To optimize the formulation of microneedles, the characteristics of swelling properties, skin insertion, solution viscosity, and needle integrity were systematically examined. Additionally, the morphology, mechanical strength, formation mechanism, skin permeability, swelling performance, biocompatibility, and in vitro transdermal drug delivery of AP-MNs were evaluated. The results indicated that the microneedles exhibited excellent mechanical-strength and hydrogel-forming properties after swelling. Further, it proved that a continuous and unblockable network channel was created based on physical entanglement and encapsulation of two materials. The 24 h cumulative permeation of acidic and alkaline model drugs, azelaic acid and matrine, were 51.73 ± 2.61% and 54.02 ± 2.85%, respectively, significantly enhancing the transdermal permeability of the two drugs. In summary, the novel auxiliary permeable microneedles prepared through a simple blending route of two materials was a promising and valuable way to improve drug permeation efficiency.

Evidence on the health benefits of vitamin C supplementation in highly polluted areas has not been evaluated. We aimed to evaluate whether dietary vitamin C supplementation can improve vascular health linked to particulate matter (PM) exposure. A randomised double-blind crossover trial involving 58 health young adults was performed in Shijiazhuang, China in 2018. All subjects were randomly assigned to the vitamin C supplementation group (2000 mg/d) or placebo group for a week alternating with a 2 week washout period. Fifteen circulating biomarkers were measured. Linear mixed-effect model was applied to evaluate the effect of vitamin C supplementation on health outcomes. The average concentrations of PM2.5 and PM10 were 164.91 and 327.05 μg/m3, respectively. Vitamin C supplementation was significantly associated with a 19.47% decrease in interleukin-6 (IL-6), 17.30% decrease in tumour necrosis factor-a (TNF-α), 34.01% decrease in C-reactive protein (CRP), 3.37% decrease in systolic blood pressure (SBP) and 6.03% decrease in pulse pressure (PP). Furthermore, glutathione peroxidase (GSH-Px) was significantly increased by 7.15%. Sex-subgroup analysis showed that vitamin C significantly reduced TNF-α by 27.85% in male participants and significantly increased APOB by 6.28% and GSH-Px by 14.47% only in female participants. This study indicated that vitamin C supplementation may protect vascular vessels against PM exposure among healthy young adults in China.

Aims: Animal-assisted therapy (AAT) relieves pain by creating a relaxed and comfortable environment to reduce anxiety in children. Yet little is known about its effects on pain in children. This study aims to systematically evaluate the effects of AAT on pain in children. Methods: Eight databases including PubMed, Cochrane Library, Web of Science, CINAHL Complete, Chinese Biomedical Database (CBM), Weipu Database (VIP), China Knowledge Resource Integrated Database (CNKI) and Wanfang Database were retrieved, and all randomized controlled trials or controlled clinical trial using AAT on children’s pain were recruited from inception to October 2019. Two reviewers independently screened literature, extracted data and assessed the risk of bias of the included studies. RevMan 5.3 software was employed for meta-analysis. Results: Seven published studies containing 4 RCTs and 3 CCTs were included for the systematic review. The results of meta-analysis showed that AAT could reduce children’s pain when compared with the control group [MD = −0.53, 95% CI (−0.77, −0.30), P

Objective: To evaluate evidence from published systematic reviews about the effectiveness of exercise interventions on fatigue management in breast cancer patients. Methods: PubMed, Web of Science, the Cochrane Library, the Cumulative Index of Nursing and Allied Health (CINAHL), Embase databases, the China National Knowledge Infrastructure (CNKI), the Wanfang database, the China Biomedical Literature Database (CBM), and the VIP database were searched to identify relevant systematic reviews. The reviews which assessed exercise interventions on cancer-related fatigue (CRF) in breast cancer patients were included. Quality of evidence was evaluated by the Grade of Recommendation, Assessment, Development, and Evaluation (GRADE) tool. The Assessment of Multiple Systematic Reviews (AMSTAR) appraisal tool was used to evaluate the methodological quality of included systematic reviews. Results: Twenty-four systematic reviews met all the inclusion criteria. The overall mean score for AMSATR is 7.38 and ranged from 4 to 10 points. In addition, 21 reviews arrived at positive conclusions, which exercises could reduce CRF, and 3 obtained that exercise does not affect fatigue. As for GRADE, 8 of the reviews were graded as ‘moderate’, 2 of the studies were ‘very low’, and the others were ‘low’. Conclusions: Aerobic and resistance exercise can be regarded as beneficial to CRF in breast cancer patients, and limited evidence exists that yoga had an effect on reducing fatigue. The quality of the current systematic review is still far from satisfactory.

Abstract Background Knowledge of the physiologic requirement for iron, the core index for the formulation of a dietary reference intake (DRI), is of great importance for the health of a pregnant woman and her fetus, and can help a mother accurately plan her iron supplementation. However, direct measurements of the physiologic requirement for iron during pregnancy are still lacking. Method Eleven women of reproductive age from Hebei Province, China, who planned to become pregnant in the near future, were enrolled between January and March 2015 and included in the final analysis. Subjects participated in a 2-week metabolic trial in which they consumed 50 mg of the stable isotope 58Fe, and were then followed for ~ 2 years. The abundance of 58Fe and the total iron concentration in the circulation were measured using Multi-collector Inductively-Coupled Plasma Mass Spectrometry and Atomic Absorption Spectroscopy, respectively. The physiologic requirement for iron during pregnancy was then calculated by the formula derived from our previously published work. Results The mean physiologic requirement for iron in the 11 subjects, across their entire pregnancies, was 3.05 mg.d− 1 in total and 44.0 μg.kg− 1.d− 1 after adjustment for body mass. The physiologic requirements for iron in the first, second, and third trimesters were 2.04 mg.d− 1, 3.26 mg.d− 1, and 4.13 mg.d− 1, respectively. When adjusted for body mass, the physiologic requirements for iron in different trimesters were 32.3 μg.kg− 1.d− 1, 46.9 μg.kg− 1.d− 1, and 55.7 μg.kg− 1.d− 1, respectively. Conclusion We preliminarily explored the physiologic requirement for iron in pregnant women. The data demonstrated that pregnant women needed about twice iron than non-pregnant women. This research may be helpful for the design of future studies and the modification of iron DRIs. Trial registration ChiCTR, ChiCTR-OCH-14004302. Registered 14 February 2014, http://www.chictr.org.cn/showproj.aspx?proj=5267

Background and PurposeAlzheimer’s disease (AD) is a devastating neurodegenerative disorder with no cure, and available treatments are only able to postpone the progression of the disease. Mild cognitive impairment (MCI) is considered to be a transitional stage preceding AD. Therefore, prediction models for conversion from MCI to AD are desperately required. These will allow early treatment of patients with MCI before they develop AD. This study performed a systematic review and meta-analysis to summarize the reported risk prediction models and identify the most prevalent factors for conversion from MCI to AD.MethodsWe systematically reviewed the studies from the databases of PubMed, CINAHL Plus, Web of Science, Embase, and Cochrane Library, which were searched through September 2021. Two reviewers independently identified eligible articles and extracted the data. We used the Critical Appraisal and Data Extraction for Systematic Reviews of Prediction Modeling Studies (CHARMS) checklist for the risk of bias assessment.ResultsIn total, 18 articles describing the prediction models for conversion from MCI to AD were identified. The dementia conversion rate of elderly patients with MCI ranged from 14.49 to 87%. Models in 12 studies were developed using the data from the Alzheimer’s Disease Neuroimaging Initiative (ADNI). C-index/area under the receiver operating characteristic curve (AUC) of development models were 0.67–0.98, and the validation models were 0.62–0.96. MRI, apolipoprotein E genotype 4 (APOE4), older age, Mini-Mental State Examination (MMSE) score, and Alzheimer’s Disease Assessment Scale cognitive (ADAS-cog) score were the most common and strongest predictors included in the models.ConclusionIn this systematic review, many prediction models have been developed and have good predictive performance, but the lack of external validation of models limited the extensive application in the general population. In clinical practice, it is recommended that medical professionals adopt a comprehensive forecasting method rather than a single predictive factor to screen patients with a high risk of MCI. Future research should pay attention to the improvement, calibration, and validation of existing models while considering new variables, new methods, and differences in risk profiles across populations.

Objectives Our study aimed to assess the association between the Dietary Inflammatory Index (DII) and depression in the elderly over 55 years in Northern China.Methods We analysed the data of 2022 Chinese adults aged 55 and over from a community-based neurological disease cohort study from 2018 to 2019. A validated semiquantitative food frequency questionnaire was used to assess eating habits at the time of inclusion. Multiple logistic regression was used for analysis, and social demographics, lifestyle and health-related factors were adjusted.Results Among the included population, the prevalence of depression was 23.39%. Mean (SD) and range of the DII in the included population were 1.70 (1.42) and −5.20 to +5.68. The risk of depression was significantly higher in participants in the most pro-inflammatory group (quartile 4) than in the participants in the most anti-inflammatory group (quartile 1) (OR 1.53; 1.37 to 1.82; p-trend=0.01). The subgroup analysis of body mass index (BMI) showed that there is a significant association between DII and the risk of depression in overweight and obese people (p＜0.05). The restricted cubic spline results show that the OR value of depression possesses an upward trend with the increase of the DII score.Conclusions Aged patients with depression present a higher potential for dietary inflammation. Pro-inflammatory diets might increase the risk of depressive symptoms. Further research in different populations is crucial to confirm the association between DII and depression.

BackgroundDepression is a common psychiatric disorder in older adults that affects their health-related quality of life. Two percent of adults over the age of 55 suffer from major depression, and the prevalence of depression increases with age. Even in the absence of major depressive disorder, 10–15% of older adults have clinically significant depressive symptoms.ObjectivesEpidemiological studies on the association between different gender eating patterns and depression show inconsistent associations. Our study examined whether different gender eating patterns are related to depression. We consider eating patterns individually and as a joint exposure to predefined eating patterns.MethodsPrincipal component analysis (PCA) was performed on the data of the 24-h diet recall dietary intake, and the dietary pattern was determined. Linear regression models are used to explore the relationship between different diets and depression of men and women; weighted quantile sum (WQS) regression, quantile g calculation (qgcomp) and Bayesian kernel machine regression (BKMR) are performed as Secondary analysis.ResultsIn the dietary patterns model, we found that the vegetable and fruit-based diet has a significant inhibitory effect in women, and the egg-milk-based diet has a significant inhibitory effect in men. We found that when all dietary factors are above the 55th percentile, there is a significant positive correlation between multiple dietary patterns and depression risk. We also determined a positive correlation between meat and obesity risk and a negative correlation between egg and milk and vegetables and fruits.ConclusionsIn the study population, after controlling for other baseline indicators and predictors of dietary pattern exposure, a fruit and vegetable-based diet was associated with a slightly healthier and lower risk of depression, while a meat-based dietary pattern associated with a higher risk of depression, and this association effect varies between genders.

AimsSesamin, the main lignin constituent of sesame, plays a pivotal role in regulating physical state. Some studies have evidenced that the supplementation of sesamin may decrease cardiovascular disease risk. The goal of this systematic review was to summarize evidence of the effects of sesamin supplementation on obesity, blood pressure, and lipid profile in humans by performing a meta-analysis of randomized controlled trials.Data SynthesisFive databases (PubMed, Cochrane Library, EMBASE, Web of Science, and Scopus) were searched electronically from inception to July 2021 to identify randomized controlled trials that assessed the impact of sesamin on obesity, blood pressure, and lipid profile. Weighted mean difference (WMD) and standard deviation (SD) were used to present the major outcomes.ConclusionsSeven trials (n = 212 participants) were included in the overall analysis. Results showed that sesamin supplementation caused a great reduction in TC (WMD: -10.893 mg/dl, 95% CI: −19.745 to −2.041, p = 0.016), LDL-c (WMD: -8.429 mg/dl, 95% CI: −16.086 to −0.771, p = 0.031), and SBP (WMD: −3.662 mmHg, 95% CI: −6.220 to −1.105, p = 0.005), whereas it had no effect on HDL-c, TG, DBP, or weight. Subgroup analysis showed that duration, parallel design, and unhealthy status can affect TC, LDL-c, and SBP evidently. We did not discover a strong link between indicators’ changes and duration of supplementation. Sesamin can be used as an obtainable dietary supplement to improve blood pressure and blood lipids, and further as a health product to prevent cardiovascular diseases.

Objective: To comprehensively compare the effectiveness of cold and heat therapies for delayed onset muscle soreness using network meta-analysis. Methods: Eight Chinese and English databases were searched from date of establishment of the database to 31 May 2021. Cochrane risk-of-bias tool was used to analyse the included randomized controlled trials. Potential papers were screened for eligibility, and data were extracted by 2 independent researchers. Results: A total of 59 studies involving 1,367 patients were eligible for this study. Ten interventions were examined: contrast water therapy, phase change material, the novel modality of cryotherapy, cold-water immersion, hot/warm-water immersion, cold pack, hot pack, ice massage, ultrasound, and passive recovery. Network meta-analysis results showed that: (i) within 24 h after exercise, hot pack was the most effective for pain relief, followed by contrast water therapy; (ii) within 48 h, the ranking was hot pack, followed by the novel modality of cryotherapy; and (iii) over 48 h post-exercise, the effect of the novel modality of cryotherapy ranked first. Conclusion: Due to the limited quality of the included studies, further well-designed research is needed to draw firm conclusions about the effectiveness of cold and heat therapies for delayed onset muscle soreness. Lay abstract The effects of different methods of cold and heat therapy on pain in patients with delayed onset muscle soreness are debated, and there is uncertainty regard­ing the most effective of these therapies. The aim of this study was to evaluate the effects of different cold and heat treatments on pain in patients with delayed onset muscle soreness. Using network meta-analysis and rank­ing, it was found that, within 48 h post-exercise, use of hot-pack was superior to other interventions, whereas, over 48 h post-exercise, cryotherapy was the optimal intervention for pain relief in patients with delayed onset muscle soreness.

BackgroundThe intake of certain food and nutrients may play a crucial role in cognitive health. However, research on the relationship between dietary patterns and cognitive function is limited. This study aims to investigate the associations between dietary patterns and multi-dimensional cognitive functions, such as global cognitive status and related domain profiles, mild cognitive impairment (MCI), and four major subtypes of Chinese adults.MethodsUsing the baseline data from the Community-based Cohort Study on Nervous System Diseases (2018–2019), we selected 4,309 Chinese adults aged 55 years and older as subjects with complete diet, cognition, and other related data. We collected food data for the past 12 months with a valid semi-quantitative food frequency questionnaire. Diving 49 food items into 13 subgroups, we used factor analysis to derive the main dietary patterns. We evaluated cognitive functions based on the scores of the Montreal Cognitive Assessment (MoCA) and used quantile regression and multivariable logistic regression to examine the relationship between dietary patterns and cognitive-related outcomes.ResultsWe identified four dietary patterns, explaining 50.11% of the total variance: “meat-preferred” pattern, “plant-preferred” pattern, “eggs- and dairy-preferred” pattern, and “grain-preferred” pattern. After adjusting for all potential confounders, the “meat-preferred” pattern and the “plant-preferred” pattern were associated with higher scores of global cognition and several cognitive domains (p