OBJECTIVE To investigate the effects and mechanism of the Yishen paidu formula on renal fibrosis in rats with chronic renal failure （CRF） through the reactive oxygen species （ROS）/thioredoxin-interacting protein （TXNIP）/NOD-like receptor thermal protein domain associated protein 3 （NLRP3） pathway. METHODS Rats were randomly divided into control group， model group， Yishen paidu formula low-dose （Yishen paidu formula-L） group， Yishen paidu formula high-dose （Yishen paidu formula- H） group， Yishen paidu formula-H+pcDNA-NC group， and Yishen paidu formula-H+ pcDNA-TXNIP group， with 10 rats in each group. Except for control group， all other rats were fed a diet containing 0.5% adenine to establish a CRF model； the rats were then administered corresponding drugs or normal saline intragastrically or via tail vein， once daily， for 8 consecutive weeks. After the last administration， the levels of serum creatinine （Scr）， blood urea nitrogen （BUN）， ROS， superoxide dismutase （SOD）， malondialdehyde （MDA）， tumor necrosis factor-α （TNF-α）， interleukin （IL）-6， and IL-1β were measured in each group. Pathological changes in renal tissue were observed， and the protein expression levels of Collagen Ⅲ， α-smooth muscle actin （α-SMA）， transforming growth factor-β1 （TGF-β1）， TXNIP and NLRP3 in renal tissue were detected. RESULTS Compared with model group， the renal histopathological damage and fibrosis of rats in Yishen paidu formula-L group and Yishen paidu formula-H group were significantly alleviated. The levels of Scr， BUN， ROS， MDA， TNF- α， IL-6 and IL-1β， and the protein expressions of Collagen Ⅲ， α-SMA， TGF-β1， TXNIP and NLRP3 were significantly decreased， while SOD levels were significantly increased （P＜0.05）. Moreover， the changes were more pronounced in the Yishen paidu formula-H group （P＜0.05）. Compared with Yishen paidu formula-H+pcDNA-NC group， above indexes of rats in Yishen paidu formula-H+pcDNA-TXNIP group were reversed significantly （P＜0.05）. CONCLUSIONS Yishen paidu formula can inhibit renal fibrosis in CRF rats by suppressing the ROS/TXNIP/NLRP3 pathway.

Background: and Purpose Vertebrobasilar fusiform aneurysms (VBFAs) carry substantial morbidity and mortality, but optimal management for unruptured VBFAs remains unclear. We compared the safety and efficacy of conservative management (CM), stent-assisted coiling (SAC), and flow diverters (FDs) in patients with unruptured VBFAs, focusing on long-term prognosis. Methods: This study included data from a nationwide Chinese cohort of patients with vertebrobasilar dissecting aneurysms. Inverse probability of treatment weighting (IPTW) balanced confounders across groups. The primary outcome was poor prognosis (modified Rankin Scale score >2). Secondary outcomes included aneurysm rupture, ischemic stroke, compression symptoms, and VBFA-related deaths. Logistic regression estimated odds ratios (ORs) and 95% confidence intervals (CIs). Subgroup and sensitivity analyses were performed. Results: Among 1,115 patients with unruptured VBFAs, 838 (median age, 54 years; 655 men) were included. After IPTW, baseline characteristics were balanced. Median follow-up was 54 months. FD was associated with a lower risk of poor prognosis than CM (OR, 0.48 [95% CI, 0.30 to 0.77]; p=0.002), with no difference between CM and SAC. FD also reduced aneurysm rupture (OR, 0.20 [95% CI, 0.07 to 0.60]; p=0.004) and compression symptoms (OR, 0.30 [95% CI, 0.13 to 0.68]; p=0.004) versus CM. Time-to-event analyses further revealed significant differences in vertebral artery lesions and Type I–II VBFAs, whereas no significant differences were observed in basilar or vertebrobasilar junction lesions or in Type III–IV VBFAs. Conclusions Compared with CM, FD was associated with improved long-term outcomes in unruptured VBFAs, particularly in vertebral artery lesions and Type I–II VBFAs, although residual confounding cannot be excluded.

ObjectiveHepatocellular carcinoma (HCC) represents 90% of all primary liver cancers. The main risk factors associated with HCC include viral hepatitis (B and/or C), alcohol abuse, and metabolic dysfunction-associated steatotic liver disease (MASLD), which progressively advance to liver fibrosis, cirrhosis, and ultimately evolve into HCC. Surgical resection represents the most effective treatment for HCC, while recent advances in immunotherapy, including immune checkpoint inhibitors and adoptive cell therapies, have provided improved treatment prospects for patients with unresectable HCC. However, the complex metabolic heterogeneity of HCC limits the therapeutic efficacy. Metabolic intermediates acyl-CoA not only provide energy and substrates for numerous biochemical reactions but also serve as donors for protein lysine acylation, a major class of post-translational modification (PTM). Therefore, a deeper understanding of the molecular mechanisms underlying protein lysine acylation and hepatocarcinogenesis is urgently needed. MethodsThe levels of protein lysine acylation and silence information regulator 5 (SIRT5) expression levels in clinical HCC samples were analyzed by Western blot. Quantitative malonylome and succinylome of HCC samples were analyzed by antibody-based affinity enrichment coupled with tandem mass spectrometry. The proliferation of HCC cells was analyzed with Cell Counting Kit-8 (CCK-8) assays, the apoptosis was quantified by Annexin V-FITC/propidium iodide (PI) staining coupled with flow cytometry, and the ability of cells to migrate was assayed by Transwell assays. The enzymatic activity of glutathione S-transferase Mu 1 (GSTM1) was quantified. Transgenic mice with hepatic overexpression of SIRT5 were constructed using CRISPR-Cas9, and primary hepatocarcinogenesis was induced by administration of diethylnitrosamine. ResultsWestern blot analysis indicated that the expression level of SIRT5 was elevated in clinical samples from HCC patients, and the levels of lysine malonylation, glutarylation, and succinylation were significantly reduced in HCC tissues. Knockout of SIRT5 in MHCC-97H and MHCC-97L hepatoma cells suppressed cell proliferation, and increased the percentage of apoptotic cells significantly. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses of the differentially malonylome and succinylome of HCC samples revealed significant enrichment in two major classes of biological processes: core energy metabolism (e.g., glycolysis/gluconeogenesis, tricarboxylic acid metabolic process, fatty acid beta oxidation) and detoxification and oxidative stress response (e.g., response to toxic substance, chemical carcinogenesis, reactive oxygen species (ROS)). SIRT5 removes malonylation from lysine residues in GSTM1 and restores its detoxification activity, which is crucial for the survival of hepatocytes under stressed conditions. More importantly, in vivo experiment indicated that hepatic-specific overexpression of SIRT5 in mice accelerated diethylnitrosamine-induced liver fibrosis and hepatocarcinogenesis, indicating the critical role of SIRT5 in HCC progression. ConclusionThis study highlights the previously unrecognized SIRT5-GSTM1 axis as a key regulator in hepatocarcinogenesis, and suggests a potential target for the treatment of patients with HCC.

Objective To analyze the prevalence and influencing factors of work‑related musculoskeletal disorders (WMSDs) among workers in hypermarkets in a district of Shanghai City. Methods A total of 477 frontline workers from hypermarkets were selected as the study participants using a convenience sampling method. The prevalence of WMSDs during the past year was investigated using the Chinese version of the Musculoskeletal Disorders Questionnaire. Results The prevalence of WMSDs among the participants was 50.3%. The shoulder, neck and lower back were the most affected body regions, with prevalence rates of 20.6%, 18.5% and 14.9%, respectively. Multivariate logistic regression analysis showed that workers who smoked or had quit smoking had a higher risk of WMSDs than non-smokers (P<0.01). Workers who engaged in physical exercise more than three times per month after work had a lower risk of WMSDs than those who did not exercise (P<0.01). Workers in warehouse-style hypermarkets had a lower risk of WMSDs than those in traditional hypermarkets (P<0.01). The risk of WMSDs increased with increasing frequency of heavy load handling among hypermarket workers (all P<0.01). Workers who sometimes performed tasks requiring forceful use of the upper limbs or hands had a higher risk of WMSDs than those who never or rarely performed such tasks (P<0.01). Workers engaged in two-shift schedules and other shift systems had a lower risk of WMSDs than those without shift work (both P<0.05). Conclusion Workers in hypermarkets showed a relatively high prevalence of WMSDs, with the shoulder, neck and lower back being the most frequently affected regions. Smoking/cessation, physical exercise, supermarket type, heavy load handling, and forceful use of the upper limbs or hands were associated with WMSDs. Hypermarkets should implement ergonomic interventions based on job characteristics, optimize work organization, and strengthen occupational health management to reduce the prevalence of WMSDs.

Objective To explore the independent risk factors for early failure of internal mammary artery grafts after coronary artery bypass grafting (CABG), and to construct and preliminarily evaluate a risk prediction model for the decline of internal mammary artery bridges, optimizing postoperative risk stratification and management strategies for patients. Methods Patients who underwent CABG at Fuwai Hospital, Chinese Academy of Medical Sciences from January 2016 to January 2020 were retrospectively enrolled. The primary endpoint was the failure of the internal mammary artery bridge one year after surgery, and the secondary endpoint was major adverse cardiac and cerebrovascular events (MACCE) within five years after surgery, including all-cause death, myocardial infarction, stroke, and revascularization. Patients were divided into a failure group and a non-failure group based on whether there was early failure of the internal mammary artery bridge after surgery. Independent risk factors for the failure of the internal mammary artery bridge were explored through the least absolute shrinkage and selection operator regression and multivariate logistic regression, and a failure risk prediction model was constructed and cross-validated. Patients were stratified for MACCE risk according to the total score of independent risk factors, and the 5-year cumulative MACCE-free rate was drawn using the Kaplan-Meier method. Results A total of 657 patients were included, among whom there were 54 patients in the failure group, including 38 males and 16 females, with an average age of (61.85±8.03) years; there were 603 patients in the non-failure group, including 467 males and 136 females, with an average age of (60.45±8.23) years. Multivariate logistic regression analysis showed that non-left main lesion [OR=3.28, 95%CI (1.41, 7.62), P=0.006], pulsatility index (PI)>3.0 [OR=2.63, 95%CI (1.20, 5.75), P=0.016], quantitative flow ratio (QFR)>0.80 [OR=5.57, 95%CI (2.98, 10.41), P<0.001] and in-hospital complications [OR=4.02, 95%CI (1.59, 10.19), P=0.003] were independent risk factors for the failure of internal mammary artery grafts after CABG. Compared with the prediction model in previous literature [area under receiver operating characteristic curve was 0.632, 95%CI (0.588, 0.688)], the risk prediction model constructed with QFR>0.80, PI>3.0, non-left main lesion and in-hospital complications had a higher predictive ability for early failure of internal mammary artery grafts [area under curve: 0.758, 95%CI (0.707, 0.817); net reclassification index: 0.272, 95%CI (0.180, 0.370); comprehensive discriminative improvement index: 0.109, 95%CI (0.059, 0.158); P<0.05]. The risk score of independent risk factors for internal mammary artery graft failure demonstrated significant MACCE risk stratification efficiency in the 5-year patient follow-up, with the high-risk group showing a significantly higher incidence of MACCE compared to the medium and low-risk groups (P=0.001). Conclusion QFR>0.80, PI>3.0, non-left main lesions, and in-hospital complications are independent risk factors for early failure of internal mammary artery grafts after CABG. The constructed risk prediction model based on this has preliminary capabilities in predicting the risk of internal mammary artery graft failure and MACCE risk stratification, which is beneficial for the postoperative management of CABG patients and improving their mid-long term prognosis.

To evaluate long-term survival and clinical outcomes of patients with knee osteo-arthritis undergoing total knee arthroplasty (TKA) through long-term follow-up.

To analyze the occurrence of early complications after total hip arthroplasty (THA) in patients with systemic lupus erythematosus (SLE).

Objective: To explore the effect of YTH domain family protein 1(YTHDF1) on the activation, proliferation and migration of hepatic stellate cells(HSCs) by regulating mitochondrial fission mediated by mitochondrial fission protein 1(Fis1). Methods: The mouse hepatic stellate cell line JS-1 was treated with 5 ng/ml TGF-β1 for 24 h to induce its activation and proliferation, andYTHDF1-siRNA was used to construct aYTHDF1silencing model.The experiment was divided into Control group, TGF-β1 group, TGF-β1+si-NC group and TGF-β1+si-YTHDF1 group.Expression changes ofYTHDF1,Fis1and key indicators of fibrosis, type Ⅰ collagen(CollagenⅠ) and α-smooth muscle actin(α-SMA) were detected through reverse transcription quantitative polymerase chain reaction(RT-qPCR) and Western blot; CCK-8 was used to detect cell proliferation ability; Transwell migration assay and cell scratch assay were used to detect cell migration ability; immunofluorescence staining experiment was used to detect the effect ofYTHDF1onFis1-mediated mitochondrial fission; finally, JC-1 staining was used to experimentally detect the effect ofYTHDF1on mitochondrial membrane potential. Results: Compared with the Control group, RT-qPCR and Western blot experimental results showed that the expression ofYTHDF1andFis1increased in the TGF-β1 group(P<0.05,P<0.01;P<0.000 1), as well as the fibrosis markersCollagenⅠand the expression level of α-SMA increased(P<0.01;P<0.001,P<0.000 1); while adding CCK-8, the experimental results showed that the proliferation ability of HSCs in the TGF-β1 group was enhanced(P<0.000 1); Transwell experimental results showed that the migration ability of HSCs in the TGF-β1 group was enhanced(P<0.01); the cell scratch experiment results showed that the migration ability of HSCs in the TGF-β1 group was enhanced(P<0.000 1); the immunofluorescence experiment results showed that the TGF-β1 group Mito-Tracker Red staining andFis1co-localization signal increased(P<0.05); JC-1 staining experiment results showed that the mitochondrial membrane potential increased in the TGF-β1 group(P<0.01). Compared with the TGF-β1+si-NC group, RT-qPCR and Western blot experimental results showed that the expression ofYTHDF1andFis1in the TGF-β1+si-YTHDF1 group was reduced(P<0.01;P<0.001), and fibrosis markers the levels ofCollagenⅠandα-SMAwere reduced(P<0.01;P<0.001,P<0.01).CCK-8 experimental results showed that the proliferation ability of HSCs in the TGF-β1+si-YTHDF1 group was weakened(P<0.000 1); Transwell experiment results showed that the migration ability of HSCs in the TGF-β1+si-YTHDF1 group was weakened(P<0.001); cell scratch experiment results showed that the migration ability of HSCs in the TGF-β1+si-YTHDF1 group was weakened(P<0.000 1); immunofluorescence experiment results showed that the Mito-Tracker Red staining andFis1co-localization signal decreased in the TGF-β1+si-YTHDF1 group(P<0.01); JC-1 staining experiment results showed that mitochondrial membrane potential decreased in the TGF-β1+si-YTHDF1 group(P<0.05). Conclusion YTHDF1promotes the activation, proliferation and migration capabilities of HSCs by positively regulatingFis1-mediated mitochondrial fission. This suggests thatYTHDF1may be a key gene involved in regulating the activation, proliferation and migration of HSCs.

Abstract In recent years, the prevalence of overweight and obesity among children and adolescents has risen rapidly, posing a serious threat to their physical and mental health. To provide scientific, systematic, and standardized weight management guidance for overweight and obese children and adolescents, the study focuses on the core concept of healthy lifestyle intervention, integrates multidisciplinary expert opinions and research findings,and proposes a comprehensive multidisciplinary intervention framework covering scientific exercise intervention, precise nutrition and diet, optimized sleep management, and standardized psychological support. It calls for the establishment of a multi agent collaborative management mechanism led by the government, implemented by families, fostered by schools, initiated by individuals, optimized by communities, reinforced by healthcare, and coordinated by multiple stakeholders. Emphasizing a child and adolescent centered approach, the consensus advocates for comprehensive, multi level, and personalized guidance strategies to promote the internalization and maintenance of a healthy lifestyle. It serves as a reference and provides recommendations for the effective prevention and control of overweight and obesity, and enhancing the health level of children and adolescents.

Objective:To construct a predictive model of ≥ grade 2 radiation esophagitis (RE) in patients with esophageal cancer during concurrent radiochemotherapy (CRT) based on machine learning (ML) algorithm.Methods:A retrospective analysis was conducted on the clinical data of 276 patients with esophageal cancer who had received CRT at Lu'an Hospital of Anhui Medical University from January 2018 to January 2023. The occurrence of RE was evaluated according to grading criteria of RE developed by American Radiation Therapy Oncology Group, with ≥ grade 2 RE as the outcome event. After screening variables through the least absolute shrinkage and selection operator (LASSO) regression, the dataset was re-established. The dataset was then divided into training set ( n=193) and testing set ( n=83) in a 7∶3 ratio and included in four ML models: random forest (RF) , decision tree (DT) , extreme gradient boosting (XGBoost) , and support vector machine (SVM) . In the models, data training and model optimization were conducted in the training set, and model performance was evaluated in the testing set using the receiver operator characteristic (ROC) curve. The area under the curve (AUC) , accuracy, precision, sensitivity, and F1 score were calculated to assess the model. SHAP analysis was used to explain the optimal model. Results:By the end of follow-up, 91 cases (32.97%) of esophageal cancer patients had experienced ≥ grade 2 RE during CRT. There were statistically significant differences in tumor lesion length ( Z=-5.53, P<0.001) , Karnofsky performance status (KPS) score ( χ2=5.92, P=0.015) , the Eastern Cooperative Oncology Group (ECOG) score ( χ2=4.01, P=0.045) , hypertension ( χ2=15.35, P<0.001) , diabetes ( χ2=13.06, P<0.001) , white blood cell count ( Z=-6.59, P<0.001) , neutrophil count ( Z=-6.72, P<0.001) , and radiotherapy dose ( χ2=9.81, P=0.002) between ≥ grade 2 RE occurrence group ( n=91) and no occurrence group ( n=185) . After LASSO regression screening, 7 characteristic variables were ultimately selected, which were tumor lesion length, ECOG score, KPS score, neutrophil count, hypertension, diabetes, and radiotherapy dose. ROC curve analysis showed that the XGBoost model had better predictive performance, with an AUC of 0.90, accuracy of 0.82, precision of 0.80, sensitivity of 0.73, and F1 score of 0.76. The AUC, accuracy, precision, sensitivity, and F1 score of RF model were 0.89, 0.78, 0.76, 0.48, and 0.59, respectively. The AUC, accuracy, precision, sensitivity, and F1 score of DT model were 0.72, 0.72, 0.44, 0.60, and 0.52, respectively. The AUC of SVM model was 0.74, with an accuracy of 0.82, precision of 0.52, sensitivity of 0.88, and F1 score of 0.65. The XGBoost model was explained using SHAP analysis, which indicated that the tumor lesion length, neutrophil count, hypertension, diabetes, and radiotherapy dose had a strong predictive ability for the occurrence of ≥ grade 2 RE during CRT in esophageal cancer patients. Conclusions:The model established based on the XGBoost method has good predictive performance for the occurrence of ≥ grade 2 RE in esophageal cancer patients during CRT. Meanwhile, combined with SHAP analysis, it can provide an intuitive understanding of the impact of important features in the model on the outcome.