ObjectiveTo examine the influences of Shenfu injection on the endogenous metabolic byproducts in the myocardium of the rat model exhibiting chronic heart failure， thus deciphering the therapeutic mechanism of the Qi-reinforcing and Yang-warming method. MethodsSD rats were randomly allocated into a control group and a modeling group. Chronic heart failure with heart-Yang deficiency syndrome in rats was modeled by multi-point subcutaneous injection of isoproterenol， and the rats were fed for 14 days after modeling. The successfully modeled rats were randomized into model， Shenfu injection （6.0 mL·kg^-1）， and trimetazidine （10 mg·kg^-1） groups and treated with corresponding agents for 15 days. The control group and the model group were injected with equal doses of normal saline， and the samples were collected after the intervention was completed. Cardiac color ultrasound was performed. Hematoxylin-eosin （HE） staining was used to observe histopathological morphology， and the serum level of N-terminal pro-brain natriuretic peptide （NT-proBNP） was assessed by enzyme-linked immunosorbent assay （ELISA）. The mitochondrial morphological and structural changes of cardiomyocytes were observed by transmission electron microscopy， and the metabolic profiling was carried out by ultra high performance liquid chromatography-quantitative exactive-mass spectrometry （UHPLC-QE-MS）. Differential metabolites were screened and identified by orthogonal partial least squares-discriminant analysis （OPLS-DA） and other methods， and then the MetaboAnalyst database was used for further screening. The relevant biological pathways were obtained through pathway enrichment analysis. The receiver operating characteristic （ROC） curve was established to evaluate the diagnostic value of each potential biomarker for myocardial injury and the evaluation value for drug efficacy. ResultsThe results of color ultrasound showed that Shenfu Injection improved the cardiac function indexes of model rats （P<0.05）. The results of HE staining showed that Shenfu injection effectively alleviated the pathological phenomena such as myocardial tissue structure disorder and inflammatory cell infiltration in model rats. The results of ELISA showed that Shenfu injection effectively regulated the serum NT-proBNP level in the model rats. Transmission electron microscopy （TEM） showed that Shenfu injection effectively restored the mitochondrial morphological structure. The results of metabolomics showed that the metabolic phenotypes of myocardial samples presented markedly differences between groups. Nine differential metabolites could be significantly reversed in the Shenfu injection group， involving three metabolic pathways： pyruvate metabolism， histidine metabolism， and citric acid cycle （TCA cycle）. The results of ROC analysis showed that the area under the curve （AUC） values of all metabolites were between 0.75 and 1.0， indicating that the differential metabolites had high diagnostic accuracy for myocardial injury， and the changes in their expression levels could be used as potential markers for efficacy evaluation. ConclusionShenfu injection significantly alleviated the damage of cardiac function， myocardium， and mitochondrial structure in the rat model of chronic heart failure with heart-Yang deficiency syndrome by ameliorating energy metabolism remodeling. Reinforcing Qi and warming Yang is a key method for treating chronic heart failure with heart-Yang deficiency syndrome.

Objective To investigate the association between single nucleotide polymorphisms (SNPs) in the nicotinamide adenine dinucleotide phosphate-oxidase (NOX) 2 and NOX4 genes and susceptibility to noise-induced hearing loss (NIHL). Methods A total of 439 noise-exposed workers were recruited using a convenience sampling method. Based on pure-tone air conduction hearing threshold tests, participants were categorized into normal hearing, mild hearing loss, and moderate hearing loss groups, with 147, 154, 138 individuals, respectively. Peripheral venous blood samples of the workers were collected for DNA extraction. Genotyping of nine SNPs loci in NOX2 and NOX4 genes was performed using multiplex polymerase chain reaction, single-base extension, and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Results A total of seven of the nine SNPs loci conformed to Hardy-Weinberg equilibrium among the workers in the normal hearing group (all P>0.05). There was no significant difference in the genotype distribution or allele frequencies for these seven SNPs loci among workers in these three groups (all P>0.05). Ordinal logistic regression analysis showed that, after adjusting for confounders including age, sex, cumulative noise exposure, smoking, alcohol consumption, and earplug use, individuals carrying the GG genotype at rs200522762 had a lower risk of NIHL compared with those carrying the TT genotype under the codominant model (P<0.05). In the recessive model, individuals carrying the GG genotype at the rs200522762 locus had a lower risk than those carrying the GT+TT genotypes (P<0.05). Polymorphisms at the other six SNPs loci were not associated with NIHL risk (all P>0.05). Conclusion The NOX4 rs200522762 polymorphism is associated with susceptibility to NIHL.

Objective To investigate the association between birth weight and dementia risk and the mediating roles of chronic diseases,and to assess potential biological pathways underlying the birth weight-associated dementia risk based on large-scale proteomics.Methods We used data from 279 743 participants aged 40 to 69 years enrolled in the UK Biobank.Birth weight was categorized into low birth weight(≤2 500 g),normal birth weight(2 500-3 999 g),and macrosomia(≥4 000 g).Multivariable Cox proportional hazards regression models were used to assess the associations between birth weight categories and all-cause dementia and its subtypes(Alzheimer's disease and vascular dementia).Proteomics analyses were conducted to identify proteins and the potential pathways involved.Results Low birth weight was associated with higher risks for all-cause dementia and its subtypes.The hazard ratios were 1.18(95%CI,1.08-1.30)for all-cause dementia,1.14(95%CI,1.00-1.31)for Alzheimer's disease,and 1.22(95%CI,1.01-1.48)for vascular dementia.A non-linear relationship was observed between birth weight and dementia risk(P for nonlinearity<0.001).Certain cardiometabolic diseases in middle-aged adults,such as diabetes,stroke,hypertension,and dyslipidemia,played a significant mediating role in the relationship between low birth weight and dementia risk,with the mediation proportion being 6.3%to 15.8%.Proteomic analyses identified 21 proteins linked to both low birth weight and all-cause dementia risk,which were significantly enriched in the pathways for viral protein interaction with cytokines and cytokine receptors,adipocytokine signaling,and cytokine-cytokine receptor interaction.Conclusion Low birth weight is positively associated with dementia risk.Cardiometabolic diseases in middle-aged adults may mediate the relationship between low birth weight and dementia risk.A number of proteins and the associated pathways underscore the relationship between low birth weight and dementia risk.

Objective: To analyze the temporal changes in lipid levels in patients following acute pancreatitis(AP) and explore the factors associated with post-AP serum triglyceride( TG) level changes. Methods: Patients diag- nosed with AP were included in this study. Clinical data were collected retrospectively , and lipid profile data from follow-up visits after discharge were tracked. Kaplan-Meier(K-M) curves were used to stratify follow-up duration ,iodine content detection. Thyroid volume was measured using a fully digital ultrasound imaging system , and goiter prevalence was calculated. Results: A total of 141 patients with 306 follow⁃up visits were included. Spearman correlation analysis showed a mild increase in lipid levels over time post⁃discharge : TG( r = 0. 159 , P = 0. 005) , total cholesterol(TC)( r = 0. 231 , P < 0. 000 1) , high⁃density lipoprotein cholesterol( HDL⁃C) ( r = 0. 181 , P = 0. 002) , and apolipoproteinA1 ( ApoA1) ( r = 0. 371 , P <0. 000 1) . In the univariate linear mixed model , male gender(β = 0. 160 ,P = 0. 007) , body mass index(BMI) (β= 0. 017 , P = 0. 007) , diabetes history(β = 0. 138 , P = 0. 030) , smoking history(β = 0. 166 ,P = 0. 004) , and recurrent AP(β = 0. 119 , P = 0. 029) were significantly associated with Lg(TG) levels (P < 0. 05) . In the multivariate model , BMI( β = 0. 019 , P = 0. 042) , smoking history ( β = 0. 155 , P = 0. 049 ) , and recurrent AP( β =0. 148 , P = 0. 032) remained significantly positively correlated with changes in Lg(TG) levels after AP , albeit with a low correlation strength (r < 0. 200) . Conclusion Lipid levels , including TG , TC , HDL⁃C and ApoA1 , tend to increase over time in AP patients after discharge , with this trend being more pronounced in those with hypertriglyceridemic acute pancreatitis. Post⁃AP TG levels are significantly influenced by BMI at the time of onset , smoking history and recurrent AP.

Astragali Radix (AR), a traditional Chinese medicine (TCM), has demonstrated therapeutic efficacy against various diseases, including cardiovascular conditions, over centuries of use. While doxorubicin serves as an effective chemotherapeutic agent against multiple cancers, its clinical application remains constrained by significant cardiotoxicity. Research has indicated that AR exhibits protective properties against doxorubicin-induced cardiomyopathy (DIC); however, the specific bioactive components and underlying mechanisms responsible for this therapeutic effect remain incompletely understood. This investigation seeks to identify the protective bioactive components in AR against DIC and elucidate their mechanisms of action. Through network medicine analysis, astragaloside IV (AsIV) and formononetin (FMT) were identified as potential cardioprotective agents from 129 AR components. In vitro experiments using H9c2 rat cardiomyocytes revealed that the AsIV-FMT combination (AFC) effectively reduced doxorubicin-induced cell death in a dose-dependent manner, with optimal efficacy at a 1∶2 ratio. In vivo, AFC enhanced survival rates and improved cardiac function in both acute and chronic DIC mouse models. Additionally, AFC demonstrated cardiac protection while maintaining doxorubicin's anti-cancer efficacy in a breast cancer mouse model. Lipidomic and metabolomics analyses revealed that AFC normalized doxorubicin-induced lipid profile alterations, particularly by reducing fatty acid accumulation. Gene knockdown studies and inhibitor experiments in H9c2 cells demonstrated that AsIV and FMT upregulated peroxisome proliferator activated receptor γ coactivator 1α (PGC-1α) and PPARα, respectively, two key proteins involved in fatty acid metabolism. This research establishes AFC as a promising therapeutic approach for DIC, highlighting the significance of multi-target therapies derived from natural herbals in contemporary medicine.
Animals ; Doxorubicin/adverse effects* ; Saponins/administration & dosage* ; Isoflavones/pharmacology* ; Rats ; Cardiomyopathies/prevention & control* ; Mice ; Fatty Acids/metabolism* ; Myocytes, Cardiac/metabolism* ; Triterpenes/administration & dosage* ; Male ; Drugs, Chinese Herbal/administration & dosage* ; Humans ; Cardiotonic Agents/administration & dosage* ; Mice, Inbred C57BL ; Cell Line ; Astragalus Plant/chemistry* ; Astragalus propinquus

γ-Aminobutyric acid(GABA),a pivotal inhibitory neurotransmitter in the central nervous system,plays an essential role in maintaining normal ocular physiological functions.GABA and its receptors are widely distributed through-out the retina,optic nerve,and visual pathways.Research indicates that GABA dysregulation is implicated in the pathogen-esis and progression of certain ophthalmic disorders.This article provides a comprehensive exploration of the relationship between GABA and ophthalmic diseases,including myopia,amblyopia,glaucoma,and dry eye syndrome.Moreover,the potential mechanisms and recent research advances are discussed.The findings may offer novel options and chances for the diagnosis and treatment of ophthalmic diseases.

Objective:To explore the effect of vitamin D supplement on chronic musculoskeletal pain (CMP) in patients with ankylosing spondylitis (AS) through a cohort study and provide evidence for optimizing vitamin D supplement strategies in AS management.Methods:Based on the large-scale prospective cohort of the UK Biobank, a total of 1 497 middle-aged and older patients diagnosed with AS were included. Patients were categorized into three groups according to their baseline vitamin supplements usage: non-vitamin supplement group ( n=978), vitamin D supplement group ( n=65), and other vitamin supplements group ( n=454). The occurrence of CMP was obtained by baseline pain survey and follow-up data from 2019—2020 and 2022—2023. A generalized linear mixed model (GLMM) was used to analyze the association between vitamin D supplement and CMP occurrence, with odds ratio ( OR) and its 95% confidence intervals ( CI) calculated. To verify robustness of the study findings, propensity score matching was employed to match participants in the vitamin D supplementation group with those in the non-vitamin supplement group and the other vitamin supplements group for sensitivity analysis. Results:After adjusting for confounding factors such as demographic characteristics, lifestyle, and co-morbidities, GLMM analysis did not find significant association between vitamin D supplement and the risk of CMP occurrence in AS patients [ OR(95% CI)=0.85(0.48, 1.48), P=0.555]. However, GLMM analysis indicated that male AS patients had a lower likelihood of developing CMP compared to female patients [ OR(95% CI)=0.69(0.56, 0.86), P<0.001]. Additionally, current smoking [ OR(95% CI)=1.46(1.06, 2.03), P=0.022] and poorer overall health status-categorized as general [ OR(95% CI)=2.32(1.85, 2.90)] or poor [ OR(95% CI)=2.31(1.68, 3.18), P<0.001] were associated with an increased risk of CMP occurrence. In the sensitivity analysis, no significant association was observed between vitamin D supplement and CMP. Conclusion:Vitamin D supplement does not reduce the risk of CMP occurrence in middle-aged and old AS patients. However, female, smoking, and poor overall health status are identified as risk factors for CMP in AS patients. Future research should focus on large-scale real-world studies, particularly in younger AS populations, to further investigate the relationship between vitamin D supplement and CMP, thereby providing more targeted intervention strategies.

Objective:To analyze the association of sedentary time and physical activity with the risk of developing chronic obstructive pulmonary disease (COPD) in non-smoking women aged 40 years and above in Songjiang District, Shanghai.Methods:Based on a natural population-based cohort in Songjiang, a total of 18 707 non-smoking women who were aged 40 years and above and without COPD at baseline survey were enrolled in the study. Cox proportional risk regression model was used to analyze the associations of the duration of sedentary behavior, physical activity with the risk for COPD at baseline survey, and the hazard ratio ( HR) of risk for COPD and its 95% CI were calculated. Stratified analyses were performed based on age, BMI, history of respiratory diseases and so on. Sensitivity analyses were conducted by excluding the cases diagnosed with COPD within one year after the baseline survey. Results:As of March 31, 2024, a total of 691 new COPD cases had been recorded after a median follow-up time of 6.96 years with an incidence density of 53.22 per 10 000 person-years. After adjusting for relevant confounders, in the tertile subgroups of sedentary time, the risk for COPD reduced by 17% in the short sedentary time group compared with the long sedentary time group ( HR=0.83,95% CI:0.70-0.99). Compared with the low physical activity level and long sedentary time group, the risk for COPD reduced by 24% in the high physical activity level and short sedentary time group ( HR=0.76, 95% CI: 0.61-0.95) and by 23% in the low physical activity level and short sedentary time group ( HR=0.77, 95% CI: 0.60-0.97). Compared with the non-physical exercise and long sedentary time group, the risk for COPD reduced by 28% in the non-physical exercise and short sedentary time group ( HR=0.72, 95% CI: 0.60-0.87). These associations remained when the cases diagnosed with COPD within one year of the baseline survey were excluded. Conclusions:Increasing physical activity and reducing sedentary time have beneficial effects to prevent COPD in non-smoking women, and reducing sedentary time alone may also reduce the risk for COPD if increasing physical exercise or other physical activity is not possible.

Energy metabolism reconstruction is the new target of the treatment of heart failure. By combing the researches of Chinese medicinals for energy metabolism reconstruction of heart failure， it was found that Chinese medicinal compound formula and single Chinese medicinal have a certain role in regulating energy metabolism， mainly through three aspects， including the optimization of substrate utilization， improvement of mitochondrial structure， function， and homeostasis， and improvement of mitochondrial energy transport， so as to make the energy metabolism of the cardiomyocyte adjusted in the direction of beneficial to the organism， increasing the supply of energy， and improving the cardiac function.