BACKGROUND:Sepsis frequently results in multiple organ failure, with the liver particularly susceptible to sepsis-induced damage. The flavonoid baicalin (BA), derived from Scutellaria baicalensis, presents anti-inflammatory properties, yet its effects on liver injury in sepsis through the Cluster of Differentiation 14 (CD14)/Nuclear Factor kappa B (NF-κB) pathway remain underexplored. METHODS:Alpha Mouse Liver 12 (AML12) cells were intervened with different concentrations of BA and subsequently challenged with lipopolysaccharide (LPS) to induce inflammation. Cell viability, apoptosis, inflammatory cytokine production, and signaling pathway activation were tested by Cell Counting Kit 8 (CCK8), flow cytometry, quantitative real-time PCR (qRT-PCR) and western blotting, respectively. And immunofluorescence was employed to visualize nuclear ectopic location of NF-κB in cells. Additionally, the impact of peroxisome proliferator-activated receptor gamma (PPARγ) silencing for BA's function was explored using small interfering RNA (siRNA) techniques. RESULTS:BA significantly improved viability and decreased apoptosis in LPS-treated cells. It also downregulated tumor necrosis factor alpha (TNF-α), interleukin-1 beta (IL-1β) and IL-6, upregulated PPARγ, and diminished CD14 and phosphorylated inhibitor of kappa B alpha (p-IKBα)/IKBα levels. Silencing PPARγ reversed the protective effects of BA, underscoring the importance of PPARγ in BA's mechanism of action. CONCLUSION:BA alleviates sepsis-induced liver injury through activating PPARγ and inhibiting CD14/NF-κB pathway, highlighting its potential as a new approach to treatment sepsis.

BACKGROUND & AIMS:Studies have illustrated the role of circadian rhythms in hepatic ischemia/reperfusion injury (HIRI), but the mechanisms are poorly understood. Bmal1 plays a significant role in the circadian control of liver physiology and disease; however, its role in HIRI has not been investigated. Here, we aimed to explore the potential contribution of BMAL1 to HIRI. METHODS:The impact of ischemia/reperfusion timing (Zeitgeber time [ZT]0 vs. ZT12) on liver damage was assessed in mice with Bmal1 specifically depleted in hepatocytes or myeloid cells. RNA sequencing and other techniques were employed to explore the underlying molecular mechanisms. Additionally, we investigated the role of HSD17B13, a lipid droplet-associated protein, in BMAL1-mediated circadian control of HIRI by utilizing global knockout, hepatocyte-specific knockdown, or hepatocyte-specific humanized HSD17B13 overexpression mouse models. RESULTS:We found that initiating ischemia/reperfusion operations at ZT12 instead of ZT0 resulted in significantly more severe liver injury in wild-type mice. Bmal1 in hepatocytes, but not in myeloid cells, mediated this temporal difference. Mechanistically, BMAL1 regulates the diurnal oscillation of HIRI by directly controlling Hsd17b13 transcription via binding to E-box-like elements. Hepatocyte-specific knockdown of Hsd17b13 blunted the diurnal variation of HIRI and exacerbated ZT0 HIRI. Furthermore, depletion of the BMAL1/HSD17B13 axis may inhibit lipid degradation by blocking autophagy flux, contributing to lipid overload and exacerbating HIRI. Finally, we demonstrated that hepatocyte-specific overexpression of humanized HSD17B13 may confer protection during ZT0 HIRI but aggravate damage at ZT12. CONCLUSIONS:Our study uncovers a pivotal role of hepatocyte BMAL1 in modulating circadian rhythms in HIRI via HSD17B13-mediated autophagy and offers a promising strategy for preventing and treating HIRI by targeting the BMAL1/HSD17B13 axis. IMPACT AND IMPLICATIONS:This study unveils a pivotal role of the BMAL1/HSD17B13 axis in the circadian control of hepatic ischemia/reperfusion injury, providing new insights into the prevention and treatment of hepatic ischemia/reperfusion injury. The findings have scientific implications as they enhance our understanding of the circadian regulation of hepatic ischemia/reperfusion injury. Furthermore, clinically, this research offers opportunities for optimizing treatment strategies in hepatic ischemia/reperfusion injury by considering the timing of therapeutic interventions.

Hypertension is a chronic cardiovascular disease that significantly impacts human quality of life. Gut microbiota and its metabolites have been reported to be involved in lipid metabolism and blood pressure regulation, but the specific alterations and pathogenic mechanisms of gut microbiota in obesity-related hypertension (OrHTN) remain unclear. In this study, we observed a significant proliferation of Desulfobacterota and Proteobacteria, while a decrease in the abundance of several butyrate-producing bacterial genera, accompanied by decreased fecal and plasma butyrate levels in high-fat diet (HFD)-induced OrHTN rats. Histone 3 lysine 9 butyrylation (H3K9bu) modification in the kidney of OrHTN rats was reduced and downregulated the expression of the hypertension-related gene MAS1. Subsequent transplantation of cecal contents from OrHTN rats on HFD into recipient rats on a normal chow diet resulted in hypertension but without obesity. Furthermore, in vitro experiments suggested that sodium butyrate increased H3K9bu modification and the expression of MAS1 in a concentration-dependent manner. In conclusion, our findings suggest that gut microbiota may contribute to the development of OrHTN by altering the expression of hypertension-related genes through butyrate-mediated histone butyrylation. This work may provide new insights into the prevention and treatment of hypertension by targeting the regulation of gut microbiota and metabolites.

ABSTRACT Background The quantitative relationship between gait speed and mortality risk in patients with chronic kidney disease remains unclear. This study aimed to conduct a meta‐analysis to estimate the risk of mortality associated with gait speed in chronic kidney disease (CKD) patients. Methods Relevant studies published were identified through literature searches using Embase, PubMed and Web of Science. Prospective cohort studies of adult CKD patients that examined the relationship between gait speed and mortality were included. Random effects meta‐analyses based on restricted maximum likelihood to were used to calculate relative risk (RR) and 95% confidence interval (95% CI). The results of meta‐analyses were assessed using Grading of Recommendations, Assessment, Development and Evaluation framework. Results Seventeen prospective cohort studies involving 6217 CKD patients (mean age range: 51.6–81.85 years; 44.3%–84% male) were included. Pooled analysis of 12 studies (n = 4233) showed that lower gait speed was associated with a higher risk of all‐cause mortality compared to higher gait speed (RR = 2.138; 95% CI: 1.794–2.548; p < 0.001; I2 = 16.0%; high‐certainty evidence) in CKD patients. Dose–response meta‐analysis of 6 studies (n = 1650) revealed that each 0.1 m/s increase in gait speed was associated with a 25.7% lower risk of all‐cause mortality (RR = 0.743; 95% CI: 0.580–0.955; p = 0.018; I2 = 45.0%; high‐certainty evidence). Conclusions Slower gait speed is a strong predictor of all‐cause mortality in CKD patients, including those undergoing dialysis or kidney transplantation. Gait speed assessment should be incorporated into routine clinical evaluations to identify high‐risk patients and guide interventions aimed at improving physical function and survival outcomes. Trial Registration: PROSPERO registration number: CRD42022340135

OBJECTIVE:This study aims to establish and validate a nomogram model for the all-cause mortality rate in patients with diabetic nephropathy (DN). METHODS:We analyzed data from the National Health and Nutrition Examination Survey (NHANES) spanning from 2007 to 2016. A random split of 7:3 was performed between the training and validation sets. Utilizing follow-up data until December 31, 2019, we examined the all-cause mortality rate. Cox regression models and Least Absolute Shrinkage and Selection Operator (LASSO) regression models were employed in the training cohort to develop a nomogram for predicting all-cause mortality in the studied population. Finally, various validation methods were employed to assess the predictive performance of the nomogram, and Decision Curve Analysis (DCA) was conducted to evaluate the clinical utility of the nomogram. RESULTS:After the results of LASSO regression models and Cox multivariate analyses, a total of 8 variables were selected, gender, age, poverty income ratio, heart failure, body mass index, albumin, blood urea nitrogen and serum uric acid. A nomogram model was built based on these predictors. The C-index values in training cohort of 3-year, 5-year, 10-year mortality rates were 0.820, 0.807, and 0.798. In the validation cohort, the C-index values of 3-year, 5-year, 10-year mortality rates were 0.773, 0.788, and 0.817, respectively. The calibration curve demonstrates satisfactory consistency between the two cohorts. CONCLUSION:The newly developed nomogram proves to be effective in predicting the all-cause mortality risk in patients with diabetic nephropathy, and it has undergone robust internal validation.

Background Eosinophilic granulomatosis with polyangiitis (EGPA), a rare but life-threatening systemic vasculitis, is distinguished by marked eosinophilia and presents with diverse symptoms, including asthma, cutaneous purpura, ecchymosis, skin necrosis, cardiac lesions, peripheral neuropathy, and necrotizing vasculitis. The etiology of EGPA involves a complex interaction among humoral, adaptive, innate, and allergic immune responses. Standard treatment employs prolonged high-dose glucocorticoid therapy, which is critical for survival; however, some patients' symptoms cannot be relieved. Case report This case report details the medical management of an 11-year-old patient with EGPA, who was at risk of bilateral lower limb amputation due to differential arterial occlusion and severe, necrotizing vasculitis-induced gangrene in both feet. Treatment modalities administered included systemic infusion of Umbilical Cord Mesenchymal Stem Cells (UC-MSCs), targeted gastrocnemius muscle injections, and application of a Placenta-Derived Mesenchymal Stem Cells (PD-MSCs) hydrogel. Results After receiving a four-month regimen of allogeneic mesenchymal stem cell therapy via intravenous and local administration, the patient showed normalized eosinophil counts, reestablished blood flow in the dorsal arteries, and marked improvement in foot ulcerations. Conclusion Mesenchymal stem cell therapy is a promising option for severe EGPA cases refractory to glucocorticoids.

Benign prostatic hyperplasia (BPH) is a condition commonly observed in aging males. Inflammatory and metabolic factors are pivotal in the development and progression of BPH. The degree to which the effects of 91 inflammation-related proteins on BPH are mediated by 1400 plasma metabolites remains ambiguous. Our research analyzed the impact of these traits utilizing genetic evidence.Two-sample Mendelian randomization (MR) and multivariable MR (MVMR) were utilized in our study to infer the genetic causal effect of inflammation-related proteins on BPH, with metabolites serving as mediators. Increased levels of IL-2 were linked to a heightened incidence of BPH (beta = 0.071, OR:1.074, 95% CI [1.002-1.152], p = 0.045), whereas lower concentrations of N6,N6-dimethyllysine were associated with decreased risk (beta 1=-0.127, p = 0.02; beta 2=-0.039, p = 0.008). The mediation effect was 0.005 (95% CI [0.0004, 0.012], OR: 1.005, 95% CI [1.000, 1.012]), accounting for 7.04% of the total effect. subsequently, we examined the phenotypic co-localization of the two pairings independently, revealing that the posterior probability of rs145516501 associated with IL-2 and BPH was 80.7%, whereas the posterior likelihood of rs4917820 linked to N6,N6-dimethyllysine levels and BPH was 95.9%. The research indicated that N6,N6-dimethyllysine levels seem to influence the causative relationship between IL-2 and BPH. These results elucidate the complex interplay between inflammation-related proteins and metabolism in the context of BPH, offering novel diagnostic and therapeutic avenues and enhancing our comprehension of the disease's etiology for prospective research.

Objective: The purpose of this study is to establish a predictive model of cognitive impairment in elderly people with diabetes.Methods: We analyzed a total of 878 elderly patients with diabetes who were part of the National Health and Nutrition Examination Survey (NHANES) from 2011 to 2014. The data were randomly divided into training and validation cohorts at a ratio of 6:4. The least absolute shrinkage and selection operator (LASSO) logistic regression analysis to identify independent risk factors and construct a prediction nomogram for cognitive impairment. The performance of the nomogram was assessed using receiver operating characteristic (ROC) curve and calibration curve. Decision curve analysis (DCA) was performed to evaluate the clinical utility of the nomogram.Results: LASSO logistic regression was used to screen eight variables, age, race, education, poverty income ratio (PIR), aspartate aminotransferase (AST), blood urea nitrogen (BUN), serum uric acid (SUA), and heart failure (HF). A nomogram model was built based on these predictors. The ROC analysis of our training set yielded an area under the curve (AUC) of 0.786, while the validation set showed an AUC of 0.777. The calibration curve demonstrated a good fit between the two groups. Furthermore, the DCA indicated that the model has a favorable net benefit when the risk threshold exceeds 0.2.Conclusion: The newly developed nomogram has proved to be an important tool for accurately predicting cognitive impairment in elderly patients with diabetes, providing important information for targeted prevention and intervention measures.

Objectives The purpose of this review is to summarise the evidence from a systematic review and meta-analysis of observational studies that objectively measure daily steps and health outcomes.Design This is an umbrella review.Data sources PubMed, Embase, Scopus, the Cochrane Library and Web of Science databases were searched through 31 January 2024.Eligibility We included systematic reviews of observational studies (with or without meta-analysis) that assessed the association of objectively measured daily steps with human health-related outcomes. Methodological quality was assessed using ‘A MeaSurement Tool to Assess systematic Reviews 2’.Results A total of 10 systematic reviews and 6 health outcomes were included after excluding irrelevant and duplicate studies. Higher daily steps were associated with more benefits than harms for a range of health-related outcomes, including all-cause mortality, cardiovascular event, skeletal muscle lesions, metabolic diseases and respiratory disease. A dose-response analysis showed that an increase of 500–1000 steps per day was associated with lower all-cause mortality and cardiovascular events. Beneficial associations were also found in patients with asthma and acutely hospitalised older adults. Conversely, one study within a systematic review suggested that higher daily steps (≥10 000) might be associated with an increased 52% risk of meniscal pathologies in individuals without knee osteoarthritis. However, one study within a systematic review suggested a potential increased risk of meniscal pathologies in individuals without knee osteoarthritis. Specifically, those exceeding 10 000 steps per day showed a 52% increase in risk.Conclusion The results of this study suggest that daily steps are associated with a lower risk of all-cause mortality and cardiovascular events. Future research could focus on identifying specific populations that may benefit most from increased daily steps and exploring potential mechanisms to enhance our understanding of how daily steps contribute to improved health outcomes.PROSPERO registration number CRD42022347055.

Abstract Background Carotid endarterectomy (CEA) is a surgical procedure that can reduce the risk of stroke in patients with carotid artery stenosis. However, controversy still exists regarding the optimal surgical technique for CEA. Objective To compare the safety and effectiveness of different techniques. Methods Data on baseline characteristics as well as perioperative and postoperative complications from patients who underwent CEA at the Department of Vascular Surgery, Xuanwu Hospital, Capital Medical University, were retrospectively collected and analyzed. Results A total of 262 CEA patients included in study, with a total of 265 CEA operations. The mean age of 69.95 ± 7.29 (range, 44–89) years. 65 (24.5%) patients underwent cCEA, 94 (35.5%) underwent pCEA, and 106 (40.0%) underwent eCEA. The use of shunt (1.9%) and the mean operation time were lower in eCEA group (P < 0.05). eCEA was also associated with a lower incidence of postoperative hypotension, whereas pCEA was associated with a lower incidence of postoperative hypertension (P < 0.05). There was no significant difference in clinical baseline characteristics, occurrence of perioperative complications, and survival whether restenosis-free, asymptomatic or overall. Conclusions This study found that all three surgical methods are equally safe for the treatment of carotid artery stenosis and are effective in preventing stroke.

Microsomal PGE2 synthase (mPGES)-1 is the key enzyme responsible for synthesizing inflammatory prostaglandin E2 (PGE2). Our previous studies have shown that deletion mPGES-1 in myeloid cells hinders atherogenesis, suppresses vascular proliferative response to injury and enhances survival after myocardial infarction. Here we aimed to further explore the influence of myeloid cell mPGES-1 deletion in abdominal aortic aneurysm (AAA) formation. The AAA was triggered by applying 0.5 M calcium phosphate (CaPO4) to the infrarenal aorta of both myeloid mPGES-1 knockout (Mac-mPGES-1-KO) and their littermate control Mac-mPGES-1-WT mice. AAA induction was assessed by calculating the expansion of the infrarenal aortic diameter 4 weeks after CaPO4 application. The maximum diameters of the aortas were measured by morphometry and the mean maximal diameters were calculated. Paraffin sections of the infrarenal aortas were examined for morphological analysis and immunohistochemical staining. The results showed that myeloid cell mPGES-1 deletion significantly mitigated AAA formation, including reducing expansion of the infrarenal aorta, preventing elastic lamellar degradation, and decreasing aortic calcium deposition. Immunohistochemical staining further indicated that macrophage infiltration and matrix metalloproteinase 2 (MMP2) expression was attenuated in the Mac-mPGES-1-KO aortas. Consistently, in vitro experiments showed that expression of pro-inflammatory cytokines and MMPs was significantly reduced when mPGES-1 was lacking in the primary cultured peritoneal macrophages. These data altogether demonstrated that deletion of mPGES-1 in myeloid cells may attenuate AAA formation and targeting myeloid cell mPGES-1 could potentially offer an effective strategy for the treatment and prevention of vascular inflammatory diseases.

PurposeFemoropopliteal artery disease (FPAD) is a common vascular disease that usually requires surgical treatment. The aim of this study was to apply predictive modeling to develop predictive models for predicting clinically driven target revascularization (CD-TLR) events 1 year after intervention in patients with FPAD.Materials and methodsIn this study, clinical data were collected from a total of 484 patients who underwent FPAD endovascular intervention from 2014 to 2019. According to the inclusion and exclusion criteria, 400 patients will be finally included and assigned to the training cohort and test cohort in the ratio of 7:3. By analyzing these data through statistical methods, we will explore the effects of different factors on target revascularization events 1 year after intervention in FPAD patients, and build the corresponding prediction model of the column line graph.ResultsThe final nomogram model consisted of 5 independent predictors: history of cerebrovascular disease, lesion length >15 cm, no atherectomy device used, no medicated balloon used and procedure time. The C-index of the model was 0.766 and 0.726 for the training cohort and validation cohort, respectively. The calibration curves also showed that the model had satisfactory agreement in both cohorts.ConclusionsThe newly developed prediction model can accurately predict clinically driven target revascularization events at 1 year in patients with FPAD, providing valuable information for the development of individualized treatment plans.

This study aimed to analyze the safety and mid-term outcomes of a hybrid treatment method combining rotational atherectomy (RA) with drug-coated balloon (DCB) angioplasty in patients with femoropopliteal artery in-stent restenosis (ISR). This single-center retrospective study enrolled patients from January 2018 to March 2022 who had femoropopliteal artery in-stent restenosis treated by RA and DCB. Preoperative demographics, operative details, and postoperative 12-month follow-up outcomes were analyzed statistically. 38 consecutive patients (31 men; mean age 69.55 ± 9.18 years, range 54–91 years) with Tosaka II (n = 8) and III (n = 30) ISR were treated with RA Most patients had a high prevalence of typical vascular comorbidities. Overall, 50

Benign prostatic hyperplasia (BPH) is a chronic disease that pretends to occur in elderly men. Inflammatory and metabolic factors play a key role in the pathogenesis and progression of BPH. The extent to which effects of 91 inflammation-related proteins on BPH are mediated by 1400 plasma metabolites is unclear. In our study we examined the effects of these traits using genetic evidence. We used two-sample Mendelian randomization ( two-sample MR) and Multivariable MR (MVMR) to determine:there is a genetic causal relationship between Interleukin-2 levels (IL-2)and BPH,N6,N6-dimethyllysine levels play a mediation role:higher IL-2 was associated with higher risk of BPH(β = 0.071, OR:1.074,95%CI[1.002–1.152],p = 0.045 and lower levels of N6,N6-dimethyllysine levels (β1=-0.127 p = 0.02).The N6,N6-dimethyllysine levels (β2=-0.039,p = 0.008) was negatively genetic associated with the risk of BPH.The mediation effect was 0.005,95% confidence interval(CI) [0.0004,0.012],odds-ratio (OR) :1.005,95%CI[1.000,1.012].Then,we analyzed the phenotypic co-localization of the two pairs : IL-2—BPH and N6,N6-dimethyllysine levels—BPH, which showed that IL-2 and BPH co-locate the SNP of rs145516501 on the NO. 13 chromosome. N6,N6-dimethyllysine levels, and BPH are co-located to the SNP of rs4917820 on the NO. 10 chromosome.The mediation proportion is 7.04%.The study suggested that N6,N6-dimethyllysine levels appear to mediate the causal effect of IL-2 on BPH.

OBJECTIVE:To compare perioperative and long-term safety and effectiveness between conventional carotid endarterectomy (cCEA) and patch carotid endarterectomy (pCEA) under current medical conditions. METHODS:Data on baseline characteristics as well as perioperative and long-term postoperative complications from patients who underwent cCEA or pCEA at the Department of Vascular Surgery, Xuanwu Hospital of Capital Medical University, from 2013 to 2022, were retrospectively collected and analyzed. RESULTS:A total of 248 CEA patients were included in our study. The majority of patients (87.3%) were male, and mean age was 63.6 ± 7.6 (range, 40-81) years; 104 patients (41.9%) underwent cCEA, while 144 (58.1%) underwent pCEA. Between the cCEA and pCEA groups, there were no significant differences in clinical baseline characteristics, occurrence of perioperative or long-term (median, 42.5 [range, 7 to 120] months) complications, and survival whether restenosis-free, asymptomatic or overall. CONCLUSIONS:In a single-center experience, conventional and patch CEA approaches appear similarly safe and effective.

This review evaluates the effectiveness of nutritional supplementation combined with exercise training on frailty characteristics, physical function, and health-related quality of life in patients with chronic kidney disease (CKD). A systematic search of PubMed, Embase, Web of Science, and Scopus was conducted, identifying 7 articles (9 trials, 324 patients). Meta-analysis showed that combined interventions improved frailty characteristics, such as walking speed (mean difference: 0.09 m/s, 95% confidence interval (CI): 0.02 to 0.16) and physical functioning, including cardiorespiratory fitness (standardized mean difference: 0.56, 95% CI: 0.20 to 0.93) and lower extremity mobility (Timed Up and Go test: -1.11 s, 95% CI: -1.79 to -0.43). However, effects on body weight, fatigue, and health-related quality of life remain uncertain. Due to study heterogeneity and small sample sizes, findings should be interpreted cautiously. Larger, long-term studies are needed to confirm these results and explore additional health outcomes.

This study aimed to investigate the role of uric acid (UA) in diabetic nephropathy (DN) from epidemiological and genetic perspectives. We used data from the 2007–2016 National Health and Nutrition Examination Survey to evaluate the relationship between UA and DN risk using weighted multivariate-adjusted logistic regression. Subsequently, a two-sample Mendelian randomization study was conducted using genome-wide association study summary statistics. The main inverse variance weighting (IVW) method and supplementary MR method were used to verify the causal relationship between UA and DN, and sensitivity analysis was conducted to confirm the credibility of the results. Our observational study enrolled 4363 participants with diabetes mellitus from NHANES, among them, 2682 (61.4

Abstract Background Acute respiratory distress syndrome (ARDS) is a common complication in patients with acute pancreatitis (AP), especially when patients complicated with acute kidney injury (AKI), resulting in increased duration of hospitalization and mortality. It is of potential clinical significance to develop a predictive model to identify the the high-risk patients. Method AP patients complicated with AKI from January 2019 to March 2022 were enrolled in this study and randomly divided into training cohort and validation cohort at a ratio of 2:1. The Least absolute shrinkage and selection operator(LASSO) regression and machine learning algorithms were applied to select features. A nomogram was developed based on the multivariate logistic regression. The performance of the nomogram was evaluated by AUC, calibration curves, and decision curve analysis. Results A total of 292 patients were enrolled in the study, with 206 in the training cohort and 86 in the validation cohort. Multivariate logistic analysis showed that IAP (Odds Ratio (OR)=4.60, 95%CI:1.23-18.24, p = 0.02), shock (OR = 12.99, 95%CI:3.47-64.04, p < 0.001), CRP(OR= 26.19, 95%CI:9.37-85.57, p < 0.001), LDH (OR = 13.13, 95%CI:4.76-40.42, p < 0.001) were independent predictors of ARDS. The nomogram was developed based on IAP, shock, CRP and LDH. The nomogram showed good discriminative ability with an AUC value of 0.954 and 0.995 in the training and validation cohort, respectively. The calibration curve indicating good concordance between the predicted and observed values. The DCA showed favorable net clinical benefit. Conclusion This study developed a simple model for predicting ARDS in AP patients complicated with AKI. The nomogram can help clinicians identify high-risk patients and optimize therapeutic strategies.

Abstract Background A growing number of studies showed that altered gut microbiota is associated with the pathogenesis of ARDS. However, the potential causal relationship remained unclear. Herein, we adopted a two-sample Mendelian randomization (MR) study to investigate the causal relationship between gut microbiota and ARDS. Methods We used publicly available genome-wide association study (GWAS) summary data to perform MR analysis. Gut microbiota GWAS were obtained from the MiBioGen study and summary-level GWAS dataset for ARDS were obtained from the IEU OpenGWAS Project. MR-Egger, weighted median, inverse variance weighted (IVW), simple mode and weighted mode methods were used to investigate the causal relationship and IVW method was considered as the primary approach. Additionally, a set of sensitivity analyses, including the MR-Egger intercept test, Cochran’s Q test, and leave-one-out test, were carried out to evaluate the robustness of our findings. Results Our study identified eight microbial taxa that were causally associated with ARDS risk. The increased abundance of Phylum Actinobacteria(odds ratio [OR]: 0.22, 95% confidence interval [CI]:0.07-0.68, P=0.008), genus Intestinibacter(OR: 0.40, 95% CI: 0.16–0.98, P=0.045) and genus Eubacterium ruminantium group (OR: 0.52, 95% CI: 0.27–1.00, P=0.049) were negatively associated with the risk of ARDS, while the abundance of genus Victivallis (OR: 2.55, 95% CI: 1.22–5.35, P=0.013), class Erysipelotrichia(OR:3.69 , 95% CI: 1.06-12.82, P=0.040), order Erysipelotrichales(OR:3.69, 95%CI:1.06-12.82,P=0.040), family Erysipelotrichaceae(OR: 3.69, 95% CI: 1.06-12.82, P=0.040), and genus Ruminococcaceae UCG014 (OR:2.92, 95% CI: 1.02-8.34, P=0.044) were positively correlated with the risk of ARDS. Sensitivity analysis revealed no evidence of heterogeneity and pleiotropy. Conclusions This study is the first to provide suggestive evidence for a causal relationship between certain gut microbiota and the risk of ARDS, providing valuable insights into the pathogenesis of microbiota-mediated ARDS and potential targets for ARDS treatment.

Background Frailty is common in chronic kidney disease (CKD) patients and becomes more prevalent as kidney disease progresses. This study aimed to investigate the prevalence of physical frailty and quantify the relationship between frailty and mortality risk in patients with CKD. Methods PubMed, Web of Science, Embase, Cochrane Central Register of Controlled Trials, Clinicaltrial.gov, and major renal academic conferences were systematically searched, and additional references to relevant articles were manually searched. The prevalence of physical frailty and the risk of mortality based on random-effects models were assessed using percentages and hazard ratio (HR) with a 95% confidence interval (CI). Results A total of 139 articles, including 1,675,482 participants, met the eligibility criteria for the meta-analysis. The results showed that 34.5% (95% CI 31.0 to 38.1%) of CKD patients showed signs of frailty, and 39.4% (95% CI 35.4 to 43.5%) had prefrail symptoms. Compared to non-frail patients, the risk of mortality was increased by 94.1% (95% CI 1.586 to 2.375) in frail patients and 34.5% (95% CI 1.231 to 1.469) in prefrail patients. Conclusion The high prevalence of frailty and prefrail in adults with CKD and resulting in premature death emphasize the importance of measuring frailty, which provides important prognostic information and may provide opportunities for interventions to improve the prognosis of patients with CKD.