Background In observational studies, there exists an association between obesity and epigenetic age as well as telomere length. However, varying and partially conflicting outcomes have notably arisen from distinct studies on this topic. In the present study, two-way Mendelian randomization was used to identify potential causal associations between obesity and epigenetic age and telomeres. Methods A genome-wide association study was conducted using data from individuals of European ancestry to investigate bidirectional Mendelian randomization (MR) regarding the causal relationships between obesity, as indicated by three obesity indicators (body mass index or BMI, waist circumference adjusted for BMI or WCadjBMI, and waist-to-hip ratio adjusted for BMI or WHRadjBMI), and four epigenetic age measures (HannumAge, HorvathAge, GrimAge, PhenoAge), as well as telomere length. To assess these causal associations, various statistical methods were employed, including Inverse Variance Weighted (IVW), Weighted Median, MR Egger, Weighted Mode, and Simple Mode. To address the issue of multiple testing, we applied the Bonferroni correction. These methods were used to determine whether there is a causal link between obesity and epigenetic age, as well as telomere length, and to explore potential bidirectional relationships. Forest plots and scatter plots were generated to show causal associations between exposures and outcomes. For a comprehensive visualization of the results, leave-one-out sensitivity analysis plots, individual SNP-based forest plots for MR analysis, and funnel plots were included in the presentation of the results. Results A strong causal association was identified between obesity and accelerated HannumAge, GrimAge, PhenoAge and telomere length shrinkage. The causal relationship between WCadjBMI and PhenoAge acceleration (OR: 2.099, 95%CI: 1.248—3.531, p = 0.005) was the strongest among them. However, only the p -values for the causal associations of obesity with GrimAge, PhenoAge, and telomere length met the criteria after correction using the Bonferroni multiple test. In the reverse MR analysis, there were statistically significant causal associations between HorvathAge, PhenoAge and GrimAge and BMI, but these associations exhibited lower effect sizes, as indicated by their Odds Ratios (ORs). Notably, sensitivity analysis revealed the robustness of the study results. Conclusions The present findings reveal a causal relationship between obesity and the acceleration of epigenetic aging as well as the reduction of telomere length, offering valuable insights for further scientific investigations aimed at developing strategies to mitigate the aging process in humans.

PurposeWe aimed to report the latest and largest pooled analyses and evidence updates to assess the effectiveness of telemedicine interventions for self-management (DSM) in patients with type 2 diabetes mellitus (T2DM).MethodsA systematic literature search was conducted using PubMed, Cochrane, Embase, and Web of Science in December 2023. We included randomized controlled trials (RCTs) of adults (≥18 years of age) diagnosed with T2DM where the intervention was the application of telemedicine. The Cochrane Risk of Bias Assessment was used to evaluate quality. The study’s main outcome indicators were glycosylated hemoglobin (HbA1c) and diabetes self-management (DSM) capacity.ResultsA total of 17 eligible articles, comprising 20 studies and 1,456 patients (734 in the intervention group and 722 in the control group), were included in the evidence synthesis. The baseline characteristics of both groups were similar in all outcomes. Comprehensive analyses showed post-intervention decreases in HbA1c, 2-h postprandial glucose, systolic and diastolic blood pressure, increases in Diabetes Self- Care activities, DSM competencies based on dietary and medication adherence, and improvements in overall DSM scores, all of which were statistically significant. While no statistically significant differences were observed in body mass index, lipids, and other DSM dimensions. Based on subgroup analyses, app-based experimental interventions targeting under 60 years old populations in Asia and North America were found to be more effective and less heterogeneity in the short term (<6 months of intervention).ConclusionTelemedicine interventions may assist patients with T2DM in enhancing their DSM and improving their HbA1c levels. Clinician can use various telemedicine interventions to enhance DSM in T2DM patients, considering local circumstances.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO/, CRD42024508522.

BACKGROUND AND AIM:Our aim was to explore the potential relationship between SII and obesity, as well as abdominal obesity. METHODS AND RESULTS:We utilized a weighted multivariable logistic regression model to investigate the relationship between SII and obesity, as well as abdominal obesity. Generalized additive models were employed to test for non-linear associations. Subsequently, we constructed a two-piecewise linear regression model and conducted a recursive algorithm to calculate inflection points. Additionally, subgroup analyses and interaction tests were performed. A total of 7,880 U.S. adult participants from NHANES 2011-2018 were recruited for this study. In the regression model adjusted for all confounding variables, the odds ratios (95% confidence intervals) for the association between SII/100 and obesity, as well as abdominal obesity, were 1.03 (1.01, 1.06) and 1.04 (1.01, 1.08) respectively. There was a non-linear and reverse U-shaped association between SII/100 and obesity, as well as abdominal obesity, with inflection points at 7.32 and 9.98 respectively. Significant positive correlations were observed before the inflection points, while significant negative correlations were found after the inflection points. There was a statistically significant interaction in the analysis of age, hypertension, and diabetes. Moreover, a notable interaction is observed between SII/100 and abdominal obesity within non-Hispanic Asian populations. CONCLUSIONS:In adults from the United States, there is a positive correlation between SII and the high risk of obesity, as well as abdominal obesity. Further large-scale prospective studies are needed to analyze the role of SII in obesity and abdominal obesity.

Objectives: The aim of our study was to assess the association between muscle mass and strength and depression through a cross-sectional study of the National Health and Nutrition Examination Survey from 2011 to 2014. Methods: Muscle mass was calculated by summing the lean body mass of the limbs and muscle strength was assessed by grip strength. Depression was determined by The 9-item Patient Health Questionnaire. We used weighted multivariate logistic regression models to explore the relationship between muscle mass and strength and depression. Generalized additive models were used to test for the presence of nonlinear associations. We then constructed a two-piece-wise linear regression model and performed a recursive algorithm to calculate inflection points. In addition, subgroup analyses and interaction tests were performed. Results: The study recruited 4871 adults from the United States. In regression models adjusted for all confounding variables, the OR (95 % CI) for the association between grip strength and appendicular lean mass (ALM) and depression were 0.943 (0.903, 0.985), 0.945 (0.908, 0.983), respectively. There was a non-linear association between grip strength and depression with a turning point of 46.3. The OR (95 % CI) before the turning point was 0.920 (0.872, 0.972). The interaction was statistically significant only in the age analysis. There was also a nonlinear association between ALM and depression, but no significant turning point was found. The interaction was statistically significant in the gender and BMI analyses. Conclusion: Grip strength and ALM are negatively associated with an increased likelihood of depression in US adults. Exercises for muscle mass and strength may help prevent depression.

Myocardial injury (MI) is a common occurrence in clinical practice caused by various factors such as ischemia, hypoxia, infection, metabolic abnormalities, and inflammation. Such damages are characterized by a reduction in myocardial function and cardiomyocyte death that can result in dangerous outcomes such as cardiac failure and arrhythmias. An endoplasmic reticulum stress (ERS)-induced unfolded protein response (UPR) is triggered by several stressors, and its intricate signaling networks are instrumental in both cell survival and death. Cardiac damage frequently triggers ERS in response to different types of injuries and stress. High levels of ERS can exacerbate myocardial damage by inducing necrosis and apoptosis. To target ERS in MI prevention and treatment, current medical research is focused on identifying effective therapy approaches. Traditional Chinese medicine (TCM) is frequently used because of its vast range of applications and low risk of adverse effects. Various studies have demonstrated that active components of Chinese medicines, including polyphenols, saponins, and alkaloids, can reduce myocardial cell death, inflammation, and modify the ERS pathway, thus preventing and mitigating cardiac injury. Thus, this paper aims to provide a new direction and scientific basis for targeting ERS in MI prevention and treatment. We specifically summarize recent research progress on the regulation mechanism of ERS in MI by active ingredients of TCM.

Hypertension is known to be a chronic inflammatory state and a key risk factor for heart failure, coronary heart disease, and atherosclerosis. Macrophages in the circulatory system are the main cell group that constitutes the immune system and participates in the inflammatory response. Depending on the local microenvironment, macrophages can be polarized into pro-inflammatory(M1) and anti-inflammatory(M2) phenotypes. When blood pressure is elevated, M1 macrophages can release pro-inflammatory cytokines and chemokines to generate an immune response. However, an excessive immune response can lead to tissue damage, and M2 macrophages release anti-inflammatory cytokines to promote the repair of wounds and tissue damage. It is clear that the dynamic balance between M1 and M2 macrophages resembles the traditional Chinese medicine(TCM) theory of Yin and Yang. That is, when Yin and Yang are imbalanced, the human body will exhibit pathological states, e.g., altered blood pressure rhythms. Studies have confirmed that TCM can produce positive therapeutic effects on hypertension by regulating macrophage polarization. Therefore, this study reviews the studies about the TCM regulation of macrophage polarization and summarized the mechanisms of TCM intervention in hypertension, with the aim of providing evidence for clinical treatment and ideas for scientific research design.

Diabetic cardiomyopathy(DCM) is a chronic complication of diabetes mellitus that leads to cardiac damage in the later stages of the disease, and its pathogenesis is complex, involving metabolic disorders brought about by a variety of aberrant alterations such as endoplasmic reticulum stress, oxidative stress, inflammation, and apoptosis, defects in cardiomyocyte Ca~(2+) transporter, and myocardial fibrosis. Currently, there is a lack of specific diagnosis and treatment in the clinic. Autophagy is a highly conserved scavenging mechanism that removes proteins, damaged organelles or foreign contaminants and converts them into energy and amino acids to maintain the stability of the intracellular environment. Inhibition of autophagy can cause harmful metabolites to accumulate in the cell, while over-activation of autophagy can disrupt normal cellular structures and cause cell death. Prolonged high glucose levels disrupt cardiomyocyte autophagy levels and exacerbate the development of DCM. The protective or detrimental effects of autophagy on cells ring true with the traditional Chinese medicine theory of healthy Qi and pathogenic Qi. Autophagy in the physiological state of the removal of intracellular substances and the generation of substances beneficial to the survival of cells is the inhibition of pathogenic Qi to help the performance of healthy Qi, so the organism is healthy. In the early stages of the disease, when autophagy is impaired and incapable of removing waste substances, pathogenic Qi is prevalent; In the later stages of the disease, excessive activation of autophagy can destroy normal cells, leading to a weakening of healthy Qi. Traditional Chinese medicine has the advantage of targeting multiple sites and pathways. Studies in recent years have confirmed that traditional Chinese medicine monomers or formulas can target autophagy, promote the restoration of autophagy levels, maintain mitochondrial and endoplasmic reticulum homeostasis, and reduce oxidative stress, endoplasmic reticulum stress, inflammation, and apoptosis in order to prevent and control DCM. This study provides a review of the relationship between autophagy and DCM and the intervention of traditional Chinese medicine in autophagy for the treatment of DCM, with a view to providing new clinical ideas and methods for the treatment of DCM with traditional Chinese medicine.

The development of coronary artery disease (CAD) is significantly affected by impaired endocrine and metabolic status. Under this circumstance, improved prevention and treatment of CAD may result from knowing the connection between metabolites and CAD. This study aims to delve into the causal relationship between human metabolic biomarkers and CAD by using two-sample Mendelian randomization (MR). Utilizing two-sample bidirectional MR analysis, we assessed the correlation between 1400 blood metabolites and CAD, and the metabolites data from the CLSA, encompassing 8299 participants. Metabolite analysis identified 1091 plasma metabolites and 309 ratios as instrumental variables. To evaluate the causal link between metabolites and CAD, we analyzed three datasets: ebi-a-GCST005195 (547,261 European & East Asian samples), bbj-a-159 (29,319 East Asian CAD cases & 183,134 East Asian controls), and ebi-a-GCST005194 (296,525 European & East Asian samples). To estimate causal links, we utilized the IVW method. To conduct sensitivity analysis, we used MR-Egger, Weighted Median, and MR-PRESSO. Additionally, we employed MR-Egger interception and Cochran’s Q statistic to assess potential heterogeneity and pleiotropy. What’s more, replication and reverse analyses were performed to verify the reliability of the results and the causal order between metabolites and disease. Furthermore, we conducted a pathway analysis to identify potential metabolic pathways. 59 blood metabolites and 27 metabolite ratios nominally associated with CAD (P < 0.05) were identified by IVW analysis method. A total of four known blood metabolites, namely beta-hydroxyisovaleroylcarnitine (OR 1.06, 95% CI 1.027–1.094, FDR 0.07), 1-palmitoyl-2-arachidonoyl (OR 1.07, 95% CI 1.029–1.110, FDR 0.09), 1-stearoyl-2- docosahexaenoyl (OR 1.07, 95% CI 1.034–1.113, FDR 0.07) and Linoleoyl-arachidonoyl-glycerol, (OR 1.07, 95% CI 1.036–1.105, FDR 0.05), and two metabolite ratios, namely spermidine to N-acetylputrescine ratio (OR 0.94, 95% CI 0.903–0.972, FDR 0.09) and benzoate to linoleoyl-arachidonoyl-glycerol ratio (OR 0.87, 95% CI 0.879–0.962, FDR 0.07), were confirmed as having a significant causal relationship with CAD, after correcting for the FDR method (p < 0. 1). A causal relationship was found to be established between beta -hydroxyisovalerylcarnitine and CAD with the validation in other two datasets. Moreover, multiple metabolic pathways were discovered to be associated with CAD. Our study supports the hypothesis that metabolites have an impact on CAD by demonstrating a causal relationship between human metabolites and CAD. This study is important for new strategies for the prevention and treatment of CAD.

Diabetic kidney disease (DKD), one of the most prevalent microvascular complications of diabetes, arises from dysregulated glucose and lipid metabolism induced by hyperglycemia, resulting in the deterioration of renal cells such as podocytes and tubular epithelial cells. Programmed cell death (PCD), comprising apoptosis, autophagy, ferroptosis, pyroptosis, and necroptosis, represents a spectrum of cell demise processes intricately governed by genetic mechanisms in vivo. Under physiological conditions, PCD facilitates the turnover of cellular populations and serves as a protective mechanism to eliminate impaired podocytes or tubular epithelial cells, thereby preserving renal tissue homeostasis amidst hyperglycemic stress. However, existing research predominantly elucidates individual modes of cell death, neglecting the intricate interplay and mutual modulation observed among various forms of PCD. In this comprehensive review, we delineate the diverse regulatory mechanisms governing PCD and elucidate the intricate crosstalk dynamics among distinct PCD pathways. Furthermore, we review recent advancements in understanding the pathogenesis of PCD and explore their implications in DKD. Additionally, we explore the potential of natural products derived primarily from botanical sources as therapeutic agents, highlighting their multifaceted effects on modulating PCD crosstalk, thereby proposing novel strategies for DKD treatment.

As the quality of life improves, the incidence of diabetes mellitus and its microvascular complications (DMC) continues to increase, posing a threat to people’s health and wellbeing. Given the limitations of existing treatment, there is an urgent need for novel approaches to prevent and treat DMC. Autophagy, a pivotal mechanism governing metabolic regulation in organisms, facilitates the removal of dysfunctional proteins and organelles, thereby sustaining cellular homeostasis and energy generation. Anomalous states in pancreatic β-cells, podocytes, Müller cells, cardiomyocytes, and Schwann cells in DMC are closely linked to autophagic dysregulation. Natural products have the property of being multi-targeted and can affect autophagy and hence DMC progression in terms of nutrient perception, oxidative stress, endoplasmic reticulum stress, inflammation, and apoptosis. This review consolidates recent advancements in understanding DMC pathogenesis via autophagy and proposes novel perspectives on treating DMC by either stimulating or inhibiting autophagy using natural products.

Mobile app interventions are emerging as significant tools in managing the prognosis of type 2 diabetes, demonstrating progressively greater impacts. The effectiveness of these interventions needs further evidence-based support. This study conducted a systematic review and meta-analysis of randomized controlled trials to evaluate the effectiveness of mobile app interventions in improving prognosis for patients with type 2 diabetes. We searched PubMed, Cochrane, Embase, and Web of Science for relevant studies published from inception to 18 April 2024, adhering to the Cochrane Handbook guidelines. The quality of the included studies was assessed using the Cochrane risk of bias tool. Primary outcomes measured were changes in glycated hemoglobin (HbA1c) and diabetes self-management (DSM). Secondary outcomes included changes in diastolic blood pressure (DBP), systolic blood pressure (SBP), triglycerides(TG), total cholesterol(TC), high-density lipoprotein (HDL), low-density lipoprotein (LDL), lipid profiles, fasting plasma glucose (FPG), body mass index (BMI), and Steps outcomes. Subgroup analyses were performed for the primary outcomes and for high-density lipoprotein (HDL), low-density lipoprotein (LDL), diastolic blood pressure (DBP), and systolic blood pressure (SBP). Interventions with or without interactions were also used as a basis for subgrouping. A total of 15 eligible articles involving 17 studies with 2,028 subjects (1,123 in the intervention group and 1,020 in the control group) were included in the synthesis. Interactive mobile app interventions significantly reduced HbA1c levels (SMD − 0.24; 95

BackgroundMetabolic dysregulation represents a defining characteristic of Type 2 diabetes (T2DM). Nevertheless, there remains an absence of substantial evidence establishing a direct causal link between circulating blood metabolites and the promotion or prevention of T2DM. In addressing this gap, we employed Mendelian randomization (MR) analysis to investigate the potential causal association between 1,091 blood metabolites, 309 metabolite ratios, and the occurrence of T2DM.MethodsData encompassing single-nucleotide polymorphisms (SNPs) for 1,091 blood metabolites and 309 metabolite ratios were extracted from a Canadian Genome-wide association study (GWAS) involving 8,299 participants. To evaluate the causal link between these metabolites and Type 2 diabetes (T2DM), multiple methods including Inverse Variance Weighted (IVW), Weighted Median, MR Egger, Weighted Mode, and Simple Mode were employed. p-values underwent correction utilizing False Discovery Rates (FDR). Sensitivity analyses incorporated Cochran’s Q test, MR-Egger intercept test, MR-PRESSO, Steiger test, leave-one-out analysis, and single SNP analysis. The causal effects were visualized via Circos plot, forest plot, and scatter plot. Furthermore, for noteworthy, an independent T2DM GWAS dataset (GCST006867) was utilized for replication analysis. Metabolic pathway analysis of closely correlated metabolites was conducted using MetaboAnalyst 5.0.ResultsThe IVW analysis method utilized in this study revealed 88 blood metabolites and 37 metabolite ratios demonstrating a significant causal relationship with T2DM (p < 0.05). Notably, strong causal associations with T2DM were observed for specific metabolites: 1-linoleoyl-GPE (18:2) (IVW: OR:0.930, 95% CI: 0.899–0.962, p = 2.16 × 10−5), 1,2-dilinoleoyl-GPE (18:2/18:2) (IVW: OR:0.942, 95% CI: 0.917–0.968, p = 1.64 × 10−5), Mannose (IVW: OR:1.133, 95% CI: 1.072–1.197, p = 1.02 × 10−5), X-21829 (IVW: OR:1.036, 95% CI: 1.036–1.122, p = 9.44 × 10−5), and Phosphate to mannose ratio (IVW: OR:0.870, 95% CI: 0.818–0.926, p = 1.29 × 10−5, FDR = 0.008). Additionally, metabolic pathway analysis highlighted six significant pathways associated with T2DM development: Valine, leucine and isoleucine biosynthesis, Phenylalanine metabolism, Glycerophospholipid metabolism, Alpha-Linolenic acid metabolism, Sphingolipid metabolism, and Alanine, aspartate, and glutamate metabolism.ConclusionThis study identifies both protective and risk-associated metabolites that play a causal role in the development of T2DM. By integrating genomics and metabolomics, it presents novel insights into the pathogenesis of T2DM. These findings hold potential implications for early screening, preventive measures, and treatment strategies for T2DM.

Background There is a correlation between obesity and 25-hydroxyvitamin D (25OHD) that tends to be negative. However, this relationship varies among different races. In this study, Asian adults with and without obesity were compared in terms of their levels of 25OHD. Methods We carried out a cross-sectional analysis on 2664 non-Hispanic Asian adults who participated in the National Health and Nutrition Examination Survey (NHANES) conducted between 2011 and 2018. To examine the connection between obese status, body mass index (BMI), waist circumference (WC) and weight, and 25OHD, we ran multivariate linear regression models and multivariate logistic regression models. Results After adjusting for all confounding factors, obesity status shows a significant positive correlation with vitamin D deficiency (model 3: OR = 2.318, 95% CI:1.317, 4.082). This positive correlation remains significant in males (males: OR = 2.713, 95% CI: -13.398, 5.217). In all three models, a negative association was observed between obesity status and 25OHD (model 1: β = -4.535, 95% CI: -6.987, -2.083; model 2 β = -4.249, 95% CI: -6.549, -2.039; model 3 β = -1.734, 95% CI: -7.285, 3.816). After controlling for covariates, there was a significant negative correlation between WC and 25OHD when stratified by gender and obesity status in both males with and without obesity (males with obesity: β = -1.461, 95% CI: -2.485, -0.436; males without obesity: β = -0.855. 95% CI: -1.499, -0.210). In males with obesity, there was a very strong positive connection between body weight and 25OHD (β = 0.912, 95% CI: 0.227, 1.597). In addition, neither gender’s obese individuals showed a significant link between BMI and 25OHD. Conclusion This study demonstrated a positive correlation between obesity and vitamin D deficiency and a negative correlation between obesity and 25OHD in Asian American adults. Additionally, among male obese individuals, there was a significant negative correlation between WC and 25OHD, an observation that needs to be validated in further prospective studies.

BACKGROUND:Despite abundant evidence on the epidemiological risk factors of metabolic diseases related to hyperuricemia, there is still insufficient evidence regarding the nonlinear relationship between triglyceride-glucose (TyG) index and hyperuricemia. Thus, the purpose of this research is to clarify the nonlinear connection between TyG and hyperuricemia.METHODS:From 2011 to 2018, a cross-sectional study was carried out using data from the National Health and Nutrition Examination Survey (NHANES). This study had 8572 participants in all. TyG was computed as Ln [triglycerides (mg/dL) × fasting glucose (mg/dL)/2]. The outcome variable was hyperuricemia. The association between TyG and hyperuricemia was examined using weighted multiple logistic regression, subgroup analysis, generalized additive models, smooth fitting curves, and two-piecewise linear regression models.RESULTS:In the regression model adjusting for all confounding variables, the OR (95% CI) for the association between TyG and hyperuricemia was 2.34 (1.70, 3.21). There is a nonlinear and reverse U-shaped association between TyG and hyperuricemia, with a inflection point of 9.69. The OR (95% CI) before the inflection point was 2.64 (2.12, 3.28), and after the inflection point was 0.32 (0.11, 0.98). The interaction in gender, BMI, hypertension, and diabetes analysis was statistically significant.CONCLUSION:Additional prospective studies are required to corroborate the current findings, which indicate a strong positive connection between TyG and hyperuricemia among adults in the United States.

Type 2 diabetes(T2DM) is a metabolic disorder marked by glucose toxicity, lipotoxicity, insulin resistance, and other pathological manifestations, representing a pressing global health concern. Obesity stands out as a pivotal risk factor for T2DM development. When combined with T2DM, obesity exacerbates insulin resistance and metabolic abnormalities. The disturbance in the inflammatory microenvironmental balance between adipose and pancreatic islet tissue emerges as a significant contributor to obese with T2DM development. Macrophages play a crucial role in maintaining immune homeostasis and responding to inflammation in adipose and pancreatic islet tissue. Individuals with obese with T2DM exhibit an imbalanced M1/M2 macrophage polarization, contributing to the progression of glycolipid metabolism abnormalities. Hence, restoring the equilibrium of macrophage polarization becomes imperative for obese with T2DM treatment. Scientific researchers have demonstrated that traditional Chinese medicine(TCM) therapies can effectively modulate macrophage polarization, offering a viable approach for treating obese with T2DM. In light of the existing evidence, this study systematically reviewed the research progress of TCM targeting the balance of M1/M2 macrophage polarization to ameliorate obese with T2DM, so as to furnish evidence supporting the clinical diagnosis and treatment of obese with T2DM with TCM while also contributing to the exploration of the biological basis of obese with T2DM.

Observational studies and meta-analyses have indicated a notable correlation between obesity and vitamin D deficiency, yet the causal relationship between the 2 remains contentious. This study employed a bidirectional Mendelian randomization (MR) analysis to explore the interrelation between obesity-associated body metrics: specifically body mass index (BMI), waist-to-hip ratio (WHR), body fat percentage (BFP), whole-body fat percentage (WHF), and 25-hydroxyvitamin D (25(OH)D) levels. Instrumental variables for BMI, WHR, BFP, whole body fat mass (WFM), and 25(OH)D were carefully selected based on predefined thresholds. The association between these metrics and 25(OH)D levels was assessed using the TwoSampleMR package in R 4.2.3. Analysis methods included inverse variance weighted (IVW), MR Egger regression, weighted median, weighted mode, and simple mode. Sensitivity analyses were conducted employing the TwoSampleMR and MR-PRESSO software packages in R 4.2.3 to evaluate heterogeneity and multiplicity of findings. All 4 body components exhibited statistically significant causal associations with decreased 25(OH)D levels: BMI (IVW: odds ratio [OR] = 0.912, 95% confidence interval [CI]: 0.888-0.937, P < .001), WHR (IVW: OR = 0.927, 95% CI: 0.882-0.975, P = .003), BFP (IVW: OR = 0.883, 95% CI: 0.867-0.899, P < .001), and WFM (IVW: OR = 0.850, 95% CI: 0.829-0.872, P < .001). However, no statistically significant inverse causative association was observed between these body components and 25(OH)D levels. Sensitivity analyses revealed no substantial heterogeneity or pleiotropy, ensuring robustness of the findings. This study substantiates a significant causal link between 4 obesity-related body components and decreased 25(OH)D levels, excluding reverse causality.

Diabetic kidney disease(DKD)is a prevalent and severe microvascular complication of type 2 diabetes mellitus(T2DM).Chronic microinflammation is an important factor exacerbating renal tissue damage in DKD individuals.Macrophages play a crucial role in immune-inflammatory responses,and they can transiently and reversibly polarize into the pro-inflammatory M1 phenotype and anti-inflammatory M2 phenotype based on microenvironmental differences.The imbalance in M1/M2 macrophage polarization can exacerbate DKD progression by fostering inflammatory cytokine aggregation in the glomeruli and renal interstitium.Therefore,restoring the balance of macrophage is a pivotal avenue to ameliorate the chronic microinflammation state in DKD.Macrophage polarization is a complex and dynamic process.Various information molecules and cytokines involved in the polarization process play important roles in regulating phenotypes during the progression of DKD.They are closely related to various mechanisms such as metabolism,inflammation,fibrosis,and mitochondrial autophagy in DKD.By coordinating the inflammatory responses through polarization,they play a key role in regulating inflammation in metabolic-related diseases.The complex network of pathways involved in macrophage polarization corresponds well with the multi-pathway,multi-target treatment model of traditional Chinese medicine(TCM).Active ingredients and formulas of TCM can intervene in DKD by regulating macrophage polarization.Studies on relieving renal inflammation,repairing renal tissues,and promoting renal function recovery through macrophage polarization modulation are not uncommon.Therefore,based on exis-ting evidence,this study reviews TCM in targeting M1/M2 macrophage polarization balance to improve DKD,aiming to explore the potential of macrophage polarization in regulating DKD,which is expected to provide evidence support for the clinical diagnosis and treatment of DKD with TCM as well as the exploration of its biological mechanisms.

This study aimed to evaluate the efficacy of Qi-supplementing and Yin-nourishing Chinese patent medicine in the treatment of early diabetic nephropathy(DN) by network Meta-analysis to explore the Chinese patent medicine with optimal efficacy and provide references for preventing renal deterioration and delaying the progression of early DN. Eight databases, including CNKI, Wanfang, VIP, SinoMed, PubMed, EMbase, Cochrane Library, and Web of Science, were searched for clinical randomized controlled trial(RCT) of Qi-supplementing and Yin-nourishing Chinese patent medicines in the treatment of early DN. After the literature mee-ting the inclusion criteria was screened, the quality of the literature was evaluated using the Cochrane risk-of-bias tool, and network Meta-analysis was performed using the BUGSnet package in R 4.2.1. Seventy-two research articles with a sample size of 6 344 cases were included, involving eight Chinese patent medicines and seven outcome indicators. The results of the network Meta-analysis showed that(1)in terms of improving urinary albumin excretion rate(UAER), Chinese patent medicines combined with conventional treatment were superior to conventional treatment, and Qiyao Xiaoke Capsules + conventional treatment was optimal.(2)In terms of reducing serum crea-tinine(Scr), Bailing Capsules + conventional treatment had superior efficacy.(3)In terms of reducing 24-hour urine total protein(24hUTP), Shenyan Kangfu Tablets + conventional treatment and Jinshuibao Capsules + conventional treatment had equivalent efficacy, and Shenyan Kangfu Tablets + conventional treatment was superior.(4)In terms of improving fasting blood glucose(FBG), Shenyan Kangfu Tablets + conventional treatment had superior efficacy.(5)In terms of improving total cholesterol(TC), Qiyao Xiaoke Capsules +conventional treatment had superior efficacy.(6)In terms of reducing triglyceride(TG), Bailing Capsules + conventional treatment had superior efficacy.(7)In terms of safety, the occurrence of adverse reactions was reported in seven interventions, but due to the large clinical heterogeneity, the quantitative analysis could not be performed. Overall, Qi-supplementing and Yin-nourishing Chinese patent medicines combined with conventional treatment were superior to conventional treatment alone in the treatment of early DN. The results showed that Qi-supplementing and Yin-nourishing Chinese patent medicines combined with conventional treatment had good clinical efficacy, and they could significantly reduce renal function indicators such as UAER, Scr, and 24hUTP, and reduce blood sugar and blood lipid, which can provide evidence-based support for the treatment of early DN. However, due to the differences in the quantity and quality of the included research articles, large-sample, multi-center, high-quality studies are still needed for further verification.

Objective:To analyze the medication and compatibility law of TCM compound patents in the treatment of diabetic nephropathy (DN) based on data mining method; To provide basis for research and development of new drug in clinic.Methods:TCM compound patents for DN treatment were retrieved from national patent platform. Excel 2019 was used to conduct statistical analysis on drug frequency, property and taste and meridian. SPSS Modeler 18.0 and SPSS Statistic 26.0 were used for drug association rules and clustering analysis. The complex network of co-occurrence of core drugs was constructed with Cytoscape 3.9.0, and the potential of the correlation between new prescriptions and drugs was demonstrated.Results:A total of 261 TCM compound patents were included, including 438 kinds of Chinese materia medica. High-frequency drugs included Astragali Radix, Rehmanniae Radix, Salviae Miltiorrhizae Radix et Rhizoma, Lycii Fructus, etc. Drug categories were mainly deficiency tonic drugs. The properties and tastes were mainly cold and sweet, and the meridians were mainly liver and kidney meridians. The commonly used medicinal pair was Ganoderma-Rehmannine Radix. The commonly used triple medicinal combination was Notoginseng Radix et Rhizoma-Angelicae Sinensis Radix-Ganoderma. There were 7 groups of clustering medicines, including Notoginseng Radix et Rhizoma, Ganoderma, Angelicae Sinensis Radix, Euryales Semen, Rehmanniae Radix and Lycii Fructus. There were 5 groups of potential medicines, including Campsis Flos-Caulis Tinosporae Sinensis-Kalopanacis Radix-Fimbristylis Rigiduta Nees-Padicularisdis Dissectae Radix -Korshinsk Peashrub-Alismatis Fructus-Cynanchi Wallichii Radix. The core new prescriptions for treating DN were obtained through topological attribute analysis and screening.Conclusions:The national TCM compounds patents treatment for DN is based on the pathogenesis of this disease, which is characterized by deficiency in nature and excess in superficiality. It often uses methods such as tonifying qi and spleen, nourishing yin and tonifying kidney, promoting blood circulation and resolving blood stasis to improve clinical efficacy, providing ideas for the development of new drugs.

目的 运用网状Meta分析方法,评价临床常用口服中成药治疗2型糖尿病周围神经病变的有效性及安全性.方法 计算机检索中国知网(CNKI)、万方(Wanfang)、维普(VIP)、中国生物医学文献服务系统(CBM)、PubMed、Embase、Cochrane Library、Web of Science中有关中成药干预糖尿病周围神经病变的随机对照试验(randomized controlled trial,RCT),时间跨度为建库至2022年11月10日;采用Cochrane偏倚风险评估工具对纳入研究进行质量评价;运用R 4.2.1进行网状Meta分析.结果 共纳入57项RCTs,总样本量5200例,涵盖10种口服中成药(木丹颗粒、银丹心脑通软胶囊、通心络胶囊、津力达颗粒、糖脉康颗粒、复方血栓通胶囊、复方丹参滴丸、通脉降糖胶囊、脑心通胶囊、血塞通胶囊).在改善感觉神经传导速度方面,木丹颗粒+常规治疗(conventional treatment,CT)相对较优;在改善运动神经传导速度方面,通心络胶囊+CT相对较优;在改善氧化应激反应方面,木丹颗粒+CT、复方血栓通胶囊+CT相对较优;在安全性方面,17项研究报道了共计17例不良反应发生,且试验组与对照组间无统计学差异(P＞0.05).结论 相比于常规治疗,在其基础上联用中成药治疗2型糖尿病周围神经病变在改善周围神经功能和氧化应激反应方面均有优势,其中木丹颗粒+CT各项疗效结局指标均优于对照组(P＜0.05),排名相对靠前,且安全性较高,可能为最佳治疗方案,但由于不同干预措施纳入研究质量和方法学的局限性,所得结论尚需进一步验证.