Objective To investigate the causal relationship between metabolic syndrome and breast cancer by using a bidirectional two-sample Mendelian randomization (MR) approach. Methods Genome-wide association study (GWAS) summary statistics for metabolic syndrome and breast cancer were acquired from the Integrative Epidemiology Unit GWAS database and the GWAS Catalog, with populations encompassing the United States and East Asia. A bidirectional causal design was employed: a forward analysis with metabolic syndrome as the exposure and breast cancer as the outcome, followed by a reverse analysis wherein their roles were interchanged. The inverse-variance weighting (IVW) method was primarily used for effect estimation, supplemented by MR-Egger regression, the weighted median method, the simple mode method, and the weighted mode method. Instrument variable strength was screened using the F-statistic (F>10). Robustness of the results was assessed through heterogeneity tests, horizontal pleiotropy tests, forest plots, and leave-one-out sensitivity analyses. Results The IVW analysis indicated no significant causal relationship between metabolic syndrome and breast cancer (OR=1.00, 95%CI: 0.97-1.03), P>0.05). Sensitivity analyses yielded consistent results, suggesting the good robustness of the study findings. Conclusion This study found no evidence to support a causal relationship, either positive or negative, between metabolic syndrome and breast cancer.

Objective:To explore the effects of respiratory muscle training(RMT)combined with phrenic nerve electrical stimulation(PNES)on coughing ability and lung function in stroke patients with pulmonary infection.Method:A total of 66 patients with pulmonary infection after stroke,admitted to our hospital from January 2022 to January 2024,were randomly assigned to either an observation group or a control group,with 33 cas-es in each group.During the study,three patients from each group dropped out.Both groups received conven-tional pharmacological and rehabilitation treatment.Additionally,the observation group received combined RMT and PNES,administered once a day,5 days per week,for 4 weeks.Outcome measures included:Cough peak flow rate(CPF),Clinical Pulmonary Infection Score(CPIS),and Borg Dyspnea Scale scores,assessed at baseline,1 week,2 weeks,and 4 weeks.Pulmonary function tests were performed at baseline and after 4 weeks,including maximum inspiratory pressure(MIP),maximum expiratory pressure(MEP),forced vital ca-pacity(FVC),forced expiratory volume in the first second(FEV1),maximum volume per minute(MVV).The percentages of predicted values(FVC％,FEV1％,MVV％)were calculated.Coughing ability and pulmo-nary function were compared between the groups.Result:At baseline and after 1 week of treatment,there were no significant between-group differences in CPF,CPIS,or Borg Dyspnea scores(P>0.05).However,after 2 and 4 weeks of treatment,the observation group showed significantly greater improvements in CPF,CPIS,and Borg Dyspnea scores compared to the control group(P<0.05).Furthermore,after 4 weeks of treatment,the improvement in all pulmonary function parame-ters(MIP,MEP,FVC％,FEV1％,MVV％)was significantly greater in the observation group than in the con-trol group(P<0.05).Conclusion:Respiratory muscle training combined with phrenic nerve electrical stimulation can effectively improve the coughing ability,alleviate pulmonary infection,and enhance lung function in stroke patients within a short peri-od of time,which is worthy of promotion and application in the treatment of lung infection in early stroke.

Objective:To investigate the differences and prognostic value of serum myeloid-related proteins 8 and 14 (Mrp 8/14) in patients with acute respiratory distress syndrome (ARDS) induced by pulmonary and extrapulmonary sepsis.Methods:A retrospective cohort study was conducted to collect the general clinical data of septic ARDS patients admitted to the intensive care unit (ICU) of Nanjing Hospital of Nanjing Medical University from August 2021 to February 2024. The serum levels of Mrp 8/14 were detected within 24 hours after admission. According to whether the patients died during ICU stay, the patients with pulmonary ARDS and extrapulmonary ARDS induced by sepsis were divided into survival and death groups, respectively. The differences of Mrp 8/14 and other clinical data between the two groups were compared. Logistic regression analysis was used to analyze the prognostic factors of septic patients with pulmonary ARDS and extrapulmonary ARDS. The receiver operating characteristic (ROC) curve was plotted to evaluate the predictive value of serum Mrp 8/14 for the prognosis of patients with pulmonary ARDS and extrapulmonary ARDS.Results:A total of 138 patients with sepsis-induced ARDS were enrolled in this study, including 79 patients with pulmonary ARDS and 59 patients with extrapulmonary ARDS. Compared to the death group, the level of serum Mrp 8/14 was significantly lower [Mrp 8/14: 22.90 (17.91, 30.88) μg/mL vs. 10.73 (7.15, 17.20) μg/mL, P<0.05]. Multivariate logistic regression analysis demonstrated that the serum Mrp 8/14 level was an independent risk factor for the prognosis of pulmonary ARDS patients only during the ICU stay ( OR=1.253, 95% CI: 1.110-1.414, P<0.05). ROC curve analysis showed that the area under the curve of serum Mrp 8/14 for the prediction of death in ARDS patients with pulmonary sepsis during ICU stay was 0.855 (95% CI: 0.773-0.938, P<0.05), the cut-off value was 19.230 μg/mL, the sensitivity was 0.718, the specificity was 0.925, and the Yonden index was 0.405. Conclusion:Serum Mrp 8/14 is an effective prognostic indicator for the mortality of ARDS patients with pulmonary sepsis during ICU hospitalization.

Objective:To investigate the correlation between sepsis-induced coagulopathy (SIC) scores, soluble thrombomodulin (sTM) levels, and disease severity in septic patients, and to evaluate their individual and combined predictive value for patient prognosis.Methods:This retrospective cohort study included 212 sepsis patients admitted to the ICU of Nanjing Hospital affiliated with Nanjing Medical University from April 2021 to April 2024. Clinical data collected within 24 hours of admission included demographics, laboratory parameters (routine blood tests, coagulation profiles, biochemistry, inflammatory markers), sTM levels, SOFA scores, APACHEⅡ scores, and SIC scores. Patients were stratified into survival ( n=124) and non-survival ( n=88) groups based on 30-day mortality. Intergroup comparisons were performed, and Spearman correlation analysis assessed relationships between SIC scores, sTM, and APACHEⅡ scores. Multivariate logistic regression identified prognostic factors, while ROC curve analysis evaluated the predictive performance of SIC scores, sTM, and their combination for 30-day mortality. Results:The non-survival group exhibited significantly higher levels of PCT [25.3 (10.8, 87.4)μg/L vs. 11.7 (7.0, 18.9) μg/L], APACHEⅡ scores (27.48±7.01 vs. 21.75±5.68), SIC scores [4.0 (3.5, 5.0) vs. 2.5 (1.0, 4.0)], and sTM [17.2 (11.6, 36.2) TU/mL vs. 10.3 (8.7, 14.6) TU/mL] compared to survivors (all P<0.05). Both SIC scores ( r=0.482) and sTM ( r=0.379) correlated positively with APACHE II scores ( P<0.05). Multivariate analysis identified APACHEⅡ score, PCT, sTM, and SIC score as independent prognostic predictors (all P<0.05). ROC analysis demonstrated predictive utility for SIC scores (AUC=0.733) and sTM (AUC=0.592), with SIC scores approximating APACHE II performance (AUC=0.755). The combined SIC-sTM model showed superior predictive accuracy (AUC=0.887; sensitivity=92.5%; specificity=76.5%) versus individual markers. Conclusions:SIC scores and sTM levels correlate significantly with sepsis severity. Their combined use enhances prognostic assessment, offering clinically valuable predictive performance for 30-day mortality in septic patients.

Diabetic retinopathy (DR) is one of the severe microvascular complications of diabetes, which can lead to irreversible retinal damage and significant visual impairment.Ursodeoxycholic acid (UDCA) and its derivative tauroursodeoxycholic acid (TUDCA), as hydrophilic bile acids, exhibit multiple cytoprotective effects including anti-apoptotic, anti-inflammatory, and antioxidant properties and show promising potential in the prevention and treatment of DR.This article reviews the protective effects and molecular mechanisms of UDCA/TUDCA on the retinal neurovascular unit under high glucose conditions.Studies have demonstrated that UDCA/TUDCA protects retinal neurons from high glucose-induced damage by inhibiting mitochondrial-dependent apoptotic pathways and the JNK/AP-1 signaling pathway, maintains the integrity of retinal vascular endothelial cells and pericytes by suppressing endoplasmic reticulum stress and reducing vascular leakage, and alleviates retinal inflammation by downregulating the expression of inflammatory factors and inhibiting microglial activation.Moreover, UDCA/TUDCA exerts its protective effects by binding to bile acid receptors, such as TGR5, on retinal cells and activating related signaling pathways.UDCA/TUDCA holds great potential in the treatment of DR, and future research should focus on optimizing delivery methods and dosages to provide new strategies for the early prevention and treatment of DR.

Objective:To explore the effects of respiratory muscle training(RMT)combined with phrenic nerve electrical stimulation(PNES)on coughing ability and lung function in stroke patients with pulmonary infection.Method:A total of 66 patients with pulmonary infection after stroke,admitted to our hospital from January 2022 to January 2024,were randomly assigned to either an observation group or a control group,with 33 cas-es in each group.During the study,three patients from each group dropped out.Both groups received conven-tional pharmacological and rehabilitation treatment.Additionally,the observation group received combined RMT and PNES,administered once a day,5 days per week,for 4 weeks.Outcome measures included:Cough peak flow rate(CPF),Clinical Pulmonary Infection Score(CPIS),and Borg Dyspnea Scale scores,assessed at baseline,1 week,2 weeks,and 4 weeks.Pulmonary function tests were performed at baseline and after 4 weeks,including maximum inspiratory pressure(MIP),maximum expiratory pressure(MEP),forced vital ca-pacity(FVC),forced expiratory volume in the first second(FEV1),maximum volume per minute(MVV).The percentages of predicted values(FVC％,FEV1％,MVV％)were calculated.Coughing ability and pulmo-nary function were compared between the groups.Result:At baseline and after 1 week of treatment,there were no significant between-group differences in CPF,CPIS,or Borg Dyspnea scores(P>0.05).However,after 2 and 4 weeks of treatment,the observation group showed significantly greater improvements in CPF,CPIS,and Borg Dyspnea scores compared to the control group(P<0.05).Furthermore,after 4 weeks of treatment,the improvement in all pulmonary function parame-ters(MIP,MEP,FVC％,FEV1％,MVV％)was significantly greater in the observation group than in the con-trol group(P<0.05).Conclusion:Respiratory muscle training combined with phrenic nerve electrical stimulation can effectively improve the coughing ability,alleviate pulmonary infection,and enhance lung function in stroke patients within a short peri-od of time,which is worthy of promotion and application in the treatment of lung infection in early stroke.

Severe open tibiofibular fractures account for approximately 28.1% of all open fractures. Among them, Gustilo-Anderson type IIIB/C fractures present significant clinical challenges due to associated bone and soft tissue defects, high infection rates, and risk of amputation. Inadequate preoperative assessment may lead to suboptimal emergency surgical planning or intraoperative complications. Historically, external fixation was often preferred, but this approach has been associated with limitations such as restricted joint mobility, delayed bone union, joint stiffness, and disuse osteoporosis, resulting in poor functional recovery. With advancements of debridement techniques, standardization of antibiotic use, and popularization of early soft tissue coverage, early internal fixation has gained broader acceptance. Nevertheless, controversies persist regarding the choice of fixation method, timing of definitive fixation, use of reamed versus unreamed intramedullary nailing, and necessity of fibular fixation. To standardize the diagnosis and early management of severe open tibiofibular fractures, reduce complication rates, and improve functional recovery, the Society of Microsurgery of the Chinese Medical Association organized a panel of domestic experts to develop the Evidence-based guideline for the diagnosis and early fixation of severe open tibiofibular fractures ( version 2025), using evidence-based methodology. The guidelines provided 12 recommendations covering diagnostic and early fixation strategies of severe open tibiofibular fractures, aiming to provide clinicians with scientifically grounded and standardized guidance.

Severe open tibiofibular fractures account for approximately 28.1% of all open fractures. Among them, Gustilo-Anderson type IIIB/C fractures present significant clinical challenges due to associated bone and soft tissue defects, high infection rates, and risk of amputation. Inadequate preoperative assessment may lead to suboptimal emergency surgical planning or intraoperative complications. Historically, external fixation was often preferred, but this approach has been associated with limitations such as restricted joint mobility, delayed bone union, joint stiffness, and disuse osteoporosis, resulting in poor functional recovery. With advancements of debridement techniques, standardization of antibiotic use, and popularization of early soft tissue coverage, early internal fixation has gained broader acceptance. Nevertheless, controversies persist regarding the choice of fixation method, timing of definitive fixation, use of reamed versus unreamed intramedullary nailing, and necessity of fibular fixation. To standardize the diagnosis and early management of severe open tibiofibular fractures, reduce complication rates, and improve functional recovery, the Society of Microsurgery of the Chinese Medical Association organized a panel of domestic experts to develop the Evidence-based guideline for the diagnosis and early fixation of severe open tibiofibular fractures ( version 2025), using evidence-based methodology. The guidelines provided 12 recommendations covering diagnostic and early fixation strategies of severe open tibiofibular fractures, aiming to provide clinicians with scientifically grounded and standardized guidance.

Objective To investigate the effect of osthole(Ost)on neuroinflammation in IS rats by regulating the HMGB1-RAGE signaling pathway.Methods After rat IS model was established with middle cerebral artery occlusion by intraluminal suture,40 model rats were grouped into model group,low-and high-dose Ost(Ost-L and Ost-H)groups,and Ost-H+recombinant rHMGB1(Ost-H+rHMGB1)group,with 10 rats in each groups.Another 10 rats served as sham operation group.Zea-Longa scoring was used to evaluate the neurological function.Serum nerve growth factor(NGF)and LDH levels,and hippocampal TNF-α,IL-10,and IL-1β contents were detected by ELISA.Triphenyltetrazolium chloride staining,Nissl staining,and TUNEL staining were applied respectively to observe the volume of cerebral infarction,hippocampal morphology,and apoptosis in hippocampal tissue cells.The activity of superoxide dismutase(SOD)in the hip-pocampus was detected by hydroxylamine assay,and that of catalases(CAT)was by ammonium molybdate.The content of malonic dialdehyde(MDA)was determined by thiobarbituric acid method.Western blotting was used to measure the protein expression of cleaved Caspase-3,HMGB1,RAGE,NF-κB,and p-NF-κB in brain tissue.Results The model group showed obvious damage in the hippocampal tissues,higher neurological function score,increased stroke volume percentage,serum LDH level and hippocampal TNF-α and IL-1βlevels,elevated neuronal apoptot-ic rate and MDA content,and up-regulation of cleaved Caspase-3,HMGB1,RAGE,and p-NF-κB/NF-κB proteins,while decreased serum NGF level,hippocampal IL-10 content and SOD and CAT activities when compared with the sham group(P＜0.05).Low-and high-dose Ost treatment re-sulted in obviously declined damage in the hippocampal tissue,decreased neurological function score,lower stroke volume percentage,reduced serum LDH level and hippocampal tissue TNF-αand IL-1β contents,lower neuronal apoptotic rate and MDA content,and down-regulated cleaved Caspase-3,HMGB1,RAGE,and p-NF-κB/NF-κB protein,while raised serum NGF level,hipp-ocampal IL-10 content and SOD and CAT activities when compared with the model group(265.84±34.76 pg/ml and 394.52±41.68 pg/ml vs 187.56±23.54 pg/ml,P＜0.05;41.84±5.67 pg/ml and 68.57±8.39 pg/ml vs 16.73±3.52 pg/ml,P＜0.05;87.49±12.53 U/mg and 109.86±14.67 U/mg vs 52.73±8.46 U/mg,P＜0.05;45.38±5.72 U/mg and 67.43±8.91 U/mg vs 21.54±3.47 U/mg,P＜0.05).rHMGB1 could alleviate the improvement effect of Ost on nerve damage in IS rats.Conclusion Ost can attenuate neuroinflammation,oxidative stress,and neuronal apoptosis in IS rats,which may be through its inhibiting the HMGB1-RAGE signaling pathway.