BackgroundBoth nutrition and inflammation are associated with depression, but previous studies have focused on individual factors. Here, we assessed the association between composite indices of nutrition and inflammation and depression.MethodsAdult participants selected from the National Health and Nutrition Examination Survey (NHANES) between 2005 and 2018 were chosen. The exposure variable was the Advanced Lung Cancer Inflammation Index (ALI) integrating nutrition and inflammation, categorized into low, medium, and high groups. The outcome variable was depression assessed using the Patient Health Questionnaire-9 (PHQ-9). A multivariable logistic regression model was employed to evaluate the relationship between ALI and the risk of depression.ResultsAfter extensive adjustment for covariates, in the overall population, participants with moderate and high levels of ALI had a decreased prevalence of depression compared to those with low ALI levels, with reductions of 17% (OR, 0.83; 95% CI: 0.72–0.97) and 23% (OR, 0.77; 95% CI: 0.66–0.91), respectively. Among females, participants with moderate and high ALI levels had a decreased prevalence of depression by 27% (OR, 0.73; 95% CI: 0.60–0.88) and 21% (OR, 0.79; 95% CI: 0.64–0.98), respectively, compared to those with low ALI levels, whereas no significant association was observed among males. Subgroup analyses based on females and males yielded consistent results.ConclusionIn this study, we observed a negative correlation between moderate to high levels of ALI and the prevalence of depression, along with gender differences. Specifically, in females, greater attention should be given to the nutritional and inflammatory status.

BackgroundLow levels of high-density lipoprotein cholesterol (HDL-C) are commonly seen in patients with type 2 diabetes mellitus (T2DM). However, it is unclear whether there is an independent or causal link between HDL-C levels and T2DM. This study aims to address this gap by using the The National Health and Nutrition Examination Survey (NHANES) database and Mendelian randomization (MR) analysis.Materials and methodsData from the NHANES survey (2007-2018) with 9,420 participants were analyzed using specialized software. Logistic regression models and restricted cubic splines (RCS) were used to assess the relationship between HDL-C and T2DM incidence, while considering covariates. Genetic variants associated with HDL-C and T2DM were obtained from genome-wide association studies (GWAS), and Mendelian randomization (MR) was used to evaluate the causal relationship between HDL-C and T2DM. Various tests were conducted to assess pleiotropy and outliers.ResultsIn the NHANES study, all groups, except the lowest quartile (Q1: 0.28-1.09 mmol/L], showed a significant association between HDL-C levels and reduced T2DM risk (all P < 0.001). After adjusting for covariates, the Q2 [odds ratio (OR) = 0.67, 95% confidence interval (CI): (0.57, 0.79)], Q3 [OR = 0.51, 95% CI: (0.40, 0.65)], and Q4 [OR = 0.29, 95% CI: (0.23, 0.36)] groups exhibited average reductions in T2DM risk of 23%, 49%, and 71%, respectively. In the sensitivity analysis incorporating other lipid levels, the Q4 group still demonstrates a 57% reduction in the risk of T2DM. The impact of HDL-C levels on T2DM varied with age (P for interaction = 0.006). RCS analysis showed a nonlinear decreasing trend in T2DM risk with increasing HDL-C levels (P = 0.003). In the MR analysis, HDL-C levels were also associated with reduced T2DM risk (OR = 0.69, 95% CI = 0.52-0.82; P = 1.41 × 10-13), and there was no evidence of pleiotropy or outliers.ConclusionThis study provides evidence supporting a causal relationship between higher HDL-C levels and reduced T2DM risk. Further research is needed to explore interventions targeting HDL-C levels for reducing T2DM risk.

BackgroundThis study aims to use six nutrition-related indicators to assess the relationship between nutritional status and the risk of COPD as well as the all-cause mortality rate, and to determine the most reliable predictive indicators.MethodsData from the National Health and Nutrition Examination Survey (NHANES) spanning the years 2013 to 2018 were extracted. Nutritional status was evaluated using Controlling nutritional status (CONUT) score, Geriatric Nutritional Risk Index (GNRI), Advanced Lung Cancer Inflammation Index (ALI), Prognostic Nutritional Index (PNI), Triglycerides (TG) × Total Cholesterol (TC) × Body Weight (BW) Index (TCBI), and Albumin-to-Globulin Ratio (AGR) nutritional-related indicators. Multivariate weighted logistic and Cox regression models were employed to assess the correlation between the six nutritional-related indicators and the risk of COPD and as all-cause mortality. The restricted cubic spline tests were applied to explore potential nonlinear relationships, and ROC curves and C-index analyses were conducted to compare the predictive capabilities of different indicators. Stratified analysis and propensity score matching (PSM) to assess the robustness of the results.ResultsIn this study, Lower ALI, lower GNRI, and higher CONUT scores were positively correlated with an increased risk of COPD (OR: 1.77, 95% CI: 1.10–2.84) (OR: 8.66, 95% CI: 2.95–25.5), and (OR: 5.11, 95% CI: 1.72–15.2), respectively. It was found that ALI and GNRI had a non-linear relationship with the risk of COPD. After propensity score matching (PSM), the associations between ALI, GNRI, CONUT scores, and COPD remained consistent. Lower ALI, PNI, and GNRI scores were positively associated with all-cause mortality in COPD patients (HR: 2.41, 95% CI: 1.10–5.27), (HR: 3.76, 95% CI: 1.89–7.48), and (HR: 4.55, 95% CI: 1.30–15.9), respectively, with GNRI displaying a non-linear relationship with all-cause mortality. ROC curve and C-index analyses indicated that ALI had the best predictive ability for both COPD risk and all-cause mortality.ConclusionALI, GNRI, and CONUT scores are correlated with the risk of COPD, while ALI, PNI, and GNRI scores are associated with all-cause mortality in COPD patients. Compared to other nutritional scores, ALI may provide more effective predictive value for both risk and all-cause mortality.

BACKGROUND:The gut-brain axis has garnered increasing attention, with observational studies suggesting its involvement in the disease activity and progression of inflammatory bowel disease (IBD), but the precise mechanisms remain unclear. MATERIALS AND METHODS:In this study, we aimed to investigate "novel proteins" underlying IBD in the brain using a comprehensive multi-omics analysis approach. We performed integrated analyses of proteomics and transcriptomics in the human prefrontal cortex (PFC) tissue, coupled with genome-wide association studies (GWAS) of IBD, crohn's disease (CD), and ulcerative colitis (UC). This included performing protein-wide association studies (PWAS), transcriptome-wide association studies (TWAS), Mendelian randomization (MR), and colocalization analysis to identify brain proteins associated with IBD and its subtypes. RESULTS:PWAS analyses identified and confirmation 9, 9, and 6 brain proteins strongly associated with IBD, CD, and UC, respectively. Subsequent MR analyses revealed that increased abundance of GPSM1, AUH, TYK2, SULT1A1, and FDPS, along with corresponding gene expression, led to decreased risk of IBD. For CD, increased abundance of FDPS, SULT1A1, and PDLIM4, along with corresponding gene expression, also decreased CD risk. Regarding UC, only increased abundance of AUH, along with corresponding gene expression, was significantly associated with decreased UC risk. Further TWAS and colocalization analyses at the transcriptome level supported strong associations of SULT1A1 and FDPS proteins with reduced risk of IBD and CD. CONCLUSION:The two "novel proteins," SULT1A1 and FDPS, are strongly associated with IBD and CD, elucidating their causal relationship in reducing the risk of IBD and CD. This provides new clues for identifying the pathogenesis and potential therapeutic targets for IBD and CD.

BackgroundPrevious studies have shown a significantly increased prevalence of osteoporosis (OP) in patients with type 2 diabetes mellitus (T2DM), which is closely associated with inflammation and nutrition. This study aimed to investigate the relationship between the advanced lung cancer inflammation index (ALI) and OP in patients with T2DM.MethodsThis cross-sectional analysis was conducted based on data from middle-aged and older adults aged 50 years and older with T2DM from the National Health and Nutrition Examination Survey (NHANES).Weighted multivariable logistic regression and linear regression were utilized to investigate the correlation between the ALI and OP with femur bone mineral density (BMD) in individuals with T2DM. Restricted cubic splines (RCS) were employed to assess potential nonlinear relationships, and receiver operating characteristic (ROC) curves were used to evaluate diagnostic accuracy.ResultsA total of 1596 patients with T2DM were included in this study, among whom 736 had OP. After adjusting for covariates, the multivariable logistic regression model showed that compared to participants in the fourth quartile of log2-transformed ALI, those in the first quartile had an increased prevalence of OP in T2DM (OR = 1.95, 95% CI=1.28-2.96, p < 0.01). The multivariable linear regression model indicated that a low log2-transformed ALI is associated with a low femur BMD.RCS demonstrated a linear dose-response relationship between the ALI index and OP in T2DM (p = 0.686), with the area under the ROC curve being 0.57 (95% CI: 0.54-0.60, p < 0.001), and the optimal cutoff value was 6.04.ConclusionOur findings indicate that low levels of ALI are independently associated with an increased prevalence of OP in middle-aged and older adults with T2DM in the United States. ALI may serve as a potential biomarker for assessing the prevalence of OP in middle-aged and older adults with T2DM.

BackgroundObservational studies have preliminarily revealed an association between smoking and gastroesophageal reflux disease (GERD). However, little is known about the causal relationship and shared genetic architecture between the two. This study aims to explore their common genetic correlations by leveraging genome-wide association studies (GWAS) of smoking behavior-specifically, smoking initiation (SI), never smoking (NS), ever smoking (ES), cigarettes smoked per day (CPD), age of smoking initiation(ASI) and GERD.MethodsFirstly, we conducted global cross-trait genetic correlation analysis and heritability estimation from summary statistics (HESS) to explore the genetic correlation between smoking behavior and GERD. Then, a joint cross-trait meta-analysis was performed to identify shared "pleiotropic SNPs" between smoking behavior and GERD, followed by co-localization analysis. Additionally, multi-marker analyses using annotation (MAGMA) were employed to explore the degree of enrichment of single nucleotide polymorphism (SNP) heritability in specific tissues, and summary data-based Mendelian randomization (SMR) was further utilized to investigate potential functional genes. Finally, Mendelian randomization (MR) analysis was conducted to explore the causal relationship between the smoking behavior and GERD.ResultsConsistent genetic correlations were observed through global and local genetic correlation analyses, wherein SI, ES, and CPD showed significantly positive genetic correlations with GERD, while NS and ASI showed significantly negative correlations. HESS analysis also identified multiple significantly associated loci between them. Furthermore, three novel "pleiotropic SNPs" (rs4382592, rs200968, rs1510719) were identified through cross-trait meta-analysis and co-localization analysis to exist between SI, NS, ES, ASI, and GERD, mapping the genes MED27, HIST1H2BO, MAML3 as new pleiotropic genes between SI, NS, ES, ASI, and GERD. Moreover, both smoking behavior and GERD were found to be co-enriched in multiple brain tissues, with GMPPB, RNF123, and RBM6 identified as potential functional genes co-enriched in Cerebellar Hemisphere, Cerebellum, Cortex/Nucleus accumbens in SI and GERD, and SUOX identified in Caudate nucleus, Cerebellum, Cortex in NS and GERD. Lastly, consistent causal relationships were found through MR analysis, indicating that SI, ES, and CPD increase the risk of GERD, while NS and higher ASI decrease the risk.ConclusionWe identified genetic loci associated with smoking behavior and GERD, as well as brain tissue sites of shared enrichment, prioritizing three new pleiotropic genes and four new functional genes. Finally, the causal relationship between smoking behavior and GERD was demonstrated, providing insights for early prevention strategies for GERD.

BackgroundFrailty is a complex clinical syndrome characterized by a decline in the functioning of multiple body systems and reduced adaptability to external stressors. Dietary ω-3 fatty acids are considered beneficial dietary nutrients for preventing frailty due to their anti-inflammatory and immune-regulating properties. However, previous research has yielded conflicting results, and the association between ω-6 fatty acids, the ω-6: ω-3 ratio, and frailty remains unclear. This study aims to explore the relationship between these factors using the National Health and Nutrition Examination Survey (NHANES) database.Materials and methodsSpecialized weighted complex survey design analysis software was employed to analyze data from the 2005–2014 NHANES, which included 12,315 participants. Multivariate logistic regression models and restricted cubic splines (RCS) were utilized to assess the relationship between omega intake and frailty risk in all participants. Additionally, a nomogram model for predicting frailty risk was developed based on risk factors. The reliability of the clinical model was determined by the area under the receiver operating characteristic (ROC) curve, calibration curves, and decision curve analysis (DCA).ResultsIn dietary ω-3 intake, compared to the T1 group (≤1.175 g/d), the T3 group’s intake level (>2.050 g/d) was associated with approximately 17% reduction in frailty risk in model 3, after rigorous covariate adjustments (odds ratio (OR) = 0.83, 95% confidence interval (CI): (0.70, 0.99)). In dietary ω-6 intake, the T2 group’s intake level (>11.423, ≤19.160 g/d) was associated with a 14% reduction in frailty risk compared to the T1 group (≤11.423 g/d) (OR: 0.86, 95% CI: 0.75, 1.00, p = 0.044). RCS results indicated a non-linear association between ω-3 and ω-6 intake and frailty risk. Both ROC and DCA curves demonstrated the stability of the constructed model and the effectiveness of an omega-rich diet in reducing frailty risk. However, we did not find a significant association between the ω-6: ω-3 ratio and frailty.ConclusionThis study provides support for the notion that a high intake of ω-3 and a moderate intake of ω-6 may contribute to reducing frailty risk in middle-aged and elderly individuals.

Background The emergence of obstructive sleep apnea (OSA) is marked by a growing trend towards younger individuals, while its developmental trajectory remains shrouded in uncertainty, accompanied by intricate prognostic implications. While frailty and sleep problems often coexist, the relationship between them remains unclear. Hence, this study aims to utilize the National Health and Nutrition Examination Survey (NHANES) database from 2005 to 2008 to analyze and explore the relationship between the level of frailty index (FI) and the risk of OSA incidence and survival outcomes. Materials and Methods Specialized weighted complex survey design analysis software was employed for data analysis. Multivariate logistic regression models and restricted cubic splines (RCS) were utilized to assess the association between FI and OSA incidence in all participants. Additionally, a Cox proportional hazards model was established to estimate the association between FI and the hazard ratios (HRs) for all-cause mortality and cardiovascular disease (CVD) mortality. Results A total of 8,524 participants were included in this study. Compared to the Non-frail group (FI ≤ 0.1), OSA risk increased with higher FI levels. In Model 3, adjusted for multiple covariates, the Pro-frail group (0.10.3) [OR = 2.32, 95% CI (1.55, 3.48)] exhibited an average 31%, 62%, and 132% increase in OSA risk, respectively. RCS results demonstrated a nonlinear dose-response relationship between OSA risk and FI levels, with an increasing trend (P = 0.004). The Cox model indicated that, except for the Pro-frail group, OSA-related mortality risk also increased with higher FI levels, with a more pronounced effect on CVD-related mortality. Conclusion This study supports the hypothesis that FI may be associated with an increased risk of OSA, with a higher emphasis on OSA-related mortality risk in Mildly frail and Moderately/Severely frail populations.

Objective To evaluate the causal relationship between gastroesophageal reflux disease(GERD)and obstructive sleep apnea(OSA)using two-sample Mendelian randomization(2SMR)and to identify potentially beneficial drugs and pathways for OSA from GERD treatment options.Methods The 2SMR was used as the primary analysis method,and multivariable Mendelian randomization(MVMR)was used to adjust for the potential impact of obesity on both diseases.Secondly,the DrugBank database was used to search for target genes of anti-reflux drugs used to treat GERD,and the dbSNP database was used to determine the target gene loci to identify the genetic tools of anti-reflux drugs.Significant target genes related to OSA risk were obtained through 2SMR analysis.Finally,the target genes were subjected to Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis and Gene Ontology(GO)analysis using the DAVID database.Results The genetically predicted risk of GERD was significantly associated with an increased risk of OSA[OR=1.43,95%CI=(1.33,1.54),P=5.29×10-22],and MVMR analysis showed that this result remained robust after adjusting for obesity.Four significant genes,including BCHE,DRD2,GRM5,and PTGER3,were identified,which are related to drugs such as nizatidine,bromperidol,ADX10059,and misoprostol.KEGG analysis identified three pathways.Conclusion GERD increases the risk of developing OSA,and anti-reflux drug targets can provide useful genetic clues for drug development in OSA treatment.

Background The association between exposure to environmental metals and chronic obstructive pulmonary disease (COPD) is preventing chronic lung diseases. However, little is currently known about the interaction between heavy metals and flavonoids in relation to the risk of COPD. This study aims to bridge this knowledge gap by leveraging The National Health and Nutrition Examination Survey (NHANES) database to evaluate thecorrelation between blood levels of heavy metals (cadmium, lead, mercury) and the intake of various flavonoid compounds (isoflavones, anthocyanidins, flavan-3-ols, flavanones, flavones, flavonols, total flavonoids). Additionally, appropriate dietary recommendations are provided based on the study findings. Materials and methods Cross-sectional analysis was conducted using the 2007–2010 and 2017–2018 NHANES data. Specialized weighted complex survey design analysis software was used for data analysis. Multivariate logistic regression models and restricted cubic splines (RCS) were used to evaluate the relationship between blood heavy metal levels, flavonoids intake, and COPD incidence in all participants, and to explore the effect of different levels of flavonoids intake on COPD caused by heavy metal exposure. Results A total of 7,265 adults aged ≥ 40 years were analyzed. Higher levels of blood cadmium (Cd), blood lead and Anthocyanidin (AC) intake were independently associated with an increased risk of COPD (Cd highest quantile vs. lowest: OR = 1.73, 95% CI, 1.25–2.3; Lead highest quantile vs. lowest quantile: OR = 1.44, 95% CI, 1.11–1.86; AC highest quantile vs. lowest: OR = 0.73, 95% CI, 0.54–0.99). When AC intake exceeded 11.56 mg/d, the effect of Cd exposure on COPD incidence decreased by 27%, and this finding was more significant in smokers. Conclusion Higher levels of Cd (≥ 0.45ug/L) and lead (≥ 0.172 ug/L) were positively correlated with the risk of COPD among participants aged 40 years and above, while AC intake (≥ 11.56 mg/d) could reduce the risk related to blood Cd.

BackgroundInflammation is the core of Chronic obstructive pulmonary disease (COPD) development. The systemic immune-inflammation index (SII) is a new biomarker of inflammation. However, it is currently unclear what impact SII has on COPD. This study aims to explore the relationship between SII and COPD.MethodsThis study analyzed patients with COPD aged ≥40 years from the National Health and Nutrition Examination Survey (NHANES) in the United States from 2013 to 2020. Restricted Cubic Spline (RCS) models were employed to investigate the association between Systemic immune-inflammation index (SII) and other inflammatory markers with COPD, including Neutrophil-to-Lymphocyte Ratio (NLR) and Platelet-to-Lymphocyte Ratio (PLR). Additionally, a multivariable weighted logistic regression model was utilized to assess the relationship between SII, NLR and PLR with COPD. To assess the predictive values of SII, NLR, and PLR for COPD prevalence, receiver operating characteristic (ROC) curve analysis was conducted. The area under the ROC curve (AUC) was used to represent their predictive values.ResultsA total of 10,364 participants were included in the cross-sectional analysis, of whom 863 were diagnosed with COPD. RCS models observed non-linear relationships between SII, NLR, and PLR levels with COPD risk. As covariates were systematically adjusted, it was found that only SII, whether treated as a continuous variable or a categorical variable, consistently remained positively associated with COPD risk. Additionally, SII (AUC = 0.589) slightly outperformed NLR (AUC = 0.581) and PLR (AUC = 0.539) in predicting COPD prevalence. Subgroup analyses revealed that the association between SII and COPD risk was stable, with no evidence of interaction.ConclusionSII, as a novel inflammatory biomarker, can be utilized to predict the risk of COPD among adults aged 40 and above in the United States, and it demonstrates superiority compared to NLR and PLR. Furthermore, a non-linear association exists between SII and the increased risk of COPD.

The use of circulating lipid traits as biomarkers to predict the risk of amyotrophic lateral sclerosis (ALS) is currently controversial, and the evidence-based medical evidence for the use of lipid-lowering agents, especially statins, on ALS risk remains insufficient. Our aim was to apply a Mendelian randomization (MR) approach to assess the causal impact of lipid-lowering agents and circulating lipid traits on ALS risk. Our study included primary and secondary analyses, in which the risk associations of lipid-lowering gene inhibitors, lipid traits, and ALS were assessed by the inverse variance weighting method as the primary approach. The robustness of the results was assessed using LDSC assessment, conventional MR sensitivity analysis, and used Mediating MR to explore potential mechanisms of occurrence. In the secondary analysis, the association of lipid-lowering genes with ALS was validated using the Summary data-based Mendelian Randomization (SMR) method. Our results showed strong evidence between genetic proxies for Apolipoprotein B (ApoB) inhibitor (OR = 0.76, 95

目的:运用网络药理学挖掘银翘马勃散治疗喉源性咳嗽的作用机制.方法:运用TC-MSP数据库,并将生物利用度(OB)≥30%,类药性(DL)≥0.18作为筛选条件,从而获得银翘马勃散的主要有效成分和作用靶点,同时将获得的作用靶点导入UniProt数据库提取相应的基因名称;运用Gene-Cards平台获得喉源性咳嗽的相关靶点;运用Venny 2.1.0在线工具将所获得的药物和疾病靶点取交集,并通过Cytoscape 3.8.0软件,构建中药成分-靶点网络图;运用STRING数据库构建银翘马勃散治疗喉源性咳嗽的蛋白PPI网络互作图;进行拓扑分析并筛选出银翘马勃散治疗喉源性咳嗽的核心靶点;利用Metascape数据库对药物、疾病交集核心靶点进行GO富集分析和KEGG通路富集分析.结果:筛选出银翘马勃散治疗喉源性咳嗽的76个有效成分,相对应的基因靶点215个;喉源性咳嗽相关靶点1399个;其中,木犀草素、槲皮素、山柰酚、β-谷甾醇、β-胡萝卜素、汉黄芩素、柱头甾醇等可能是银翘马勃散治疗喉源性咳嗽的关键成分;涉及AKT1、TP53、TNF、ESR1、MYC、EGFR、IL6、CAV1等26个核心靶点.KEGG通路富集结果提示这些靶点参与TNF信号通路、C型凝集素受体信号通路、RIG-I样受体信号通路、Toll 样受体信号通路、NOD样受体信号通路、IL-17 信号通路等.结论:银翘马勃散中的活性成分能通过多靶点、多通路起到治疗喉源性咳嗽的作用.

BackgroundThe association between dietary patterns and depression has gained significant attention, but the relationship between fruit intake and depression remains unclear. This study aimed to investigate the role of fruit intake in the risk of depression using data from the National Health and Nutrition Examination Survey (NHANES) and Mendelian randomization (MR) analysis, and further explore the causal relationship between them.Materials and methodsCross-sectional analysis was conducted using the 2005–2018 NHANES data. Specialized weighted complex survey design analysis software was used for multivariate logistic analysis. Additionally, genetic variants for fruit intake and depression, as well as its related neuroticism traits, from the GWAS were used as instrumental variables in MR analysis. The inverse variance weighted (IVW) method was employed as the primary analysis method to evaluate the causal relationship between them. MR-Egger regression, MR-PRESSO test, and leave-one-out analysis were conducted to assess heterogeneity and pleiotropy.ResultsIn NHANES, compared to the lowest quartile (Q1, <0.12 cup], the highest quartile (Q4, >1.49 cups) of fruit intake showed a significant reduction in the risk of depression after adjusting for relevant covariates. Model 3, after rigorous adjustment for multiple covariates, demonstrated improved predictive performance in both Receiver operating characteristic (ROC) curve and Decision curve analysis (DCA). In Model 3, the proportion of reduced depression risk associated with fruit intake reached 31% (OR = 0.69, 95% CI: 0.50–0.95). This association remained significant in the MR analysis (OR = 0.92, 95% CI = 0.87–0.96; p = 5.09E-04). Fruit intake was also associated with a decreased risk of neuroticism traits related to depression, including feeling lonely (OR = 0.82, 95% CI = 0.74–0.90; p = 2.91E-05), feeling miserable (OR = 0.79, 95% CI = 0.72–0.87; p = 2.35E-06), feeling fed-up (OR = 0.75, 95% CI = 0.68–0.83; p = 2.78E-08), irritable mood (OR = 0.89, 95% CI = 0.79–0.99; p = 0.03), and neuroticism (OR = 0.85, 95% CI = 0.76–0.96; p = 9.94E-03). The causal relationship between feeling lonely and fruit intake was bidirectional.ConclusionIncreased fruit intake has a causal effect in reducing the risk of depression and is beneficial for related psychological well-being.

Background: The causal associations between statin use and male sex hormone levels and related disorders have not been fully understood. In this study, we employed Mendelian randomization for the first time to investigate these associations. Methods: In two-sample Mendelian randomization framework, genetic proxies for hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) inhibition were identified as variants in the HMGCR gene that were associated with both levels of gene expression and low density lipoprotein cholesterol (LDL-C). We assessed the causal relationship between HMGCR inhibitor and 5 sex hormone levels/2 male-related diseases. Additionally, we investigated the association between 4 circulating lipid traits and outcomes. The “inverse variance weighting” method was used as the primary approach, and we assessed for potential heterogeneity and pleiotropy. In a secondary analysis, we revalidated the impact of HMGCR on 7 major outcomes using the summary-data-based Mendelian randomization method. Results: Our study found a significant causal association between genetic proxies for HMGCR inhibitor and decreased levels of total testosterone (TT) (LDL-C per standard deviation = 38.7mg/dL, effect = −0.20, 95% confidence interval [CI] = −0.25 to −0.15) and bioavailable testosterone (BT) (effect = −0.15, 95% CI = −0.21 to −0.10). Obesity-related factors were found to mediate this association. Furthermore, the inhibitor were found to mediate a reduced risk of prostate cancer (odds ratio = 0.81, 95%CI = 0.7–0.93) by lowering bioavailable testosterone levels, without increasing the risk of erectile dysfunction (P = .17). On the other hand, there was a causal association between increased levels of LDL-C, total cholesterol, triglycerides (TG) and decreased levels of TT, sex hormone-binding globulin, and estradiol. Conclusions: The use of HMGCR inhibitor will reduce testosterone levels and the risk of prostate cancer without the side effect of erectile dysfunction. LDL-C, total cholesterol, and TG levels were protective factors for TT, sex hormone-binding globulin, and estradiol.

Review question / Objective: The aim of this meta-analysis of randomized controlled trials is to evaluate the efficacy and safety of Guizhi Jiahoupu Xingzi Decoction in patients with bronchial asthma.Condition being studied: Bronchial asthma (BA) is characterized by chronic airway inflammation involving a variety of cells (such as eosinophils, mast cells, T lymphocytes, neutrophils, airway epithelial cells, etc.) and cellular components.A heterogeneous disease, this chronic inflammation is associated with airway hyperresponsiveness, often with widespread and variable reversible expiratory airflow limitation.According to the latest epidemiological study, more than 339 million people worldwide have BA .r.The World Health Organization (WHO) estimates that the number of asthma patients will increase to 400 million by 2025 worldwide.From researches,the prevalence of asthma is 1% to 18% worldwide.As of now, the incidence of asthma is about 4.2% in China.The number of related drugs for the clinical treatment of BA is gradually increasing, but the long-term application of glucocorticoids, β2 receptor agonists, anticholinergic drugs, leukotriene receptor antagonists and theophylline drugs can relieve asthma in the acute phase.Remarkable effects have been achieved in patients with seizures, but long-term application will lead to a decline in the therapeutic effect.The morbidity and mortality of asthma have not decreased, but have shown an upward trend, suggesting that Western medicine has obvious curative effects on the control of clinical symptoms of the disease, but cannot be cured.