Background Work-related musculoskeletal disorders (WMSDs) are a major occupational health concern, particularly among workers exposed to adverse ergonomic conditions. Manganese production involves heavy physical demands, yet research on WMSDs among manganese workers remains limited. Objective To investigate the prevalence and influencing factors of WMSDs among manganese workers in a manganese enterprise in Guangxi. Methods A cross-sectional survey was conducted from May to June 2024 on workers at a manganese factory in Guangxi. The Chinese Musculoskeletal Disorders Questionnaire was used to collect information on demographic characteristics, distribution of musculoskeletal symptoms, and work-related exposures. χ² test was applied to compare differences in positive WMSDs rates across groups, and logistic regression analysis was performed to identify associated factors. Results A total of 1476 workers were enrolled in the study after pre-determined inclusion and exclusion criteria. The overall prevalence of WMSDs was 34.15%. The most commonly affected body regions were the lower back (17.28%), neck (16.67%), and shoulders (13.82%). The results of logistic regression analysis indicated that female, older age, and education level of college or above were associated with a higher risk of WMSDs (P<0.05). Awkward working postures were significantly associated with WMSDs in corresponding body regions; in particular, awkward postures of the neck, upper limbs, trunk, and lower limbs were related to an increased risk of WMSDs in multiple body sites (P<0.05). In addition, poor lighting conditions, high workplace temperature, frequent or sustained arm support during work, and high job demands were associated with an increased risk of overall or site-specific WMSDs (P<0.05). Conclusion The high prevalence of WMSDs among manganese workers is closely associated with demographic characteristics, working postures, and work environment and organizational factors. Targeted ergonomic interventions focusing on high-risk body regions and key ergonomic exposures are warranted to reduce the risk of WMSDs among manganese workers.

A unified consensus statement on medication-related osteonecrosis of the jaw (MRONJ) has not yet been established among the Asian member countries or regions of the Asian Federation of Osteoporosis Societies (AFOS). This study aimed to develop a consensus on MRONJ in patients with osteoporosis across these countries and regions. In this study, the term “Asia-Pacific” refers specifically to the Asian member countries and regions of AFOS. A structured survey consisting of nine MRONJ-related questions was distributed across 10 countries and regions to assess the level of agreement and summarize regional perspectives. In addition, a manual literature review and voting were conducted to evaluate the current evidence on MRONJ. The key aspects of MRONJ, including definition, staging, diagnosis, pathogenesis, risk factors, management, and prevention, were generally consistent among the AFOS countries and regions. The annual incidence and incidence rate of MRONJ associated with low-dose antiresorptive therapy in patients with osteoporosis ranged from 0.025% to 0.136% and 21 to 283 cases per 100,000 person-years, respectively. However, evidence regarding the benefits of drug discontinuation before dental surgery, such as tooth extraction, remains insufficient. Large-scale, multinational studies across AFOS countries and regions are warranted to determine the incidence of MRONJ better and evaluate the impact of antiresorptive drug discontinuation before dental procedures. These findings may contribute to the devel opment of effective evidence-based strategies for preventing MRONJ in patients with osteoporosis.

BACKGROUND/OBJECTIVES: Deoxyshikonin (DSK) has been reported to inhibit tumor growth in various types of cancers, but its roles and action mechanisms in breast cancer (BC) are unclear. This study examined the anti-cancer function and mechanism of DSK in BC.MATERIALS/METHODS: MDA-MB-231 and BT549, human BC cells, were used. The cell viability and apoptosis levels were examined using Cell Counting Kit-8 experiments and flow cytometry, respectively. The expression of apoptosis-related factors (Ki-67, Bax, and Bcl-2), CD206, CD168, and proteins involved in the phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)uclear factor (NF)-κB pathway was evaluated by Western blot analysis. The cell invasion ability was determined using the Transwell experiment. The levels of interleukin (IL)-10 and transforming growth factor (TGF)-β were detected using an enzyme-linked immunosorbent assay. The in vivo functions of DSK were assessed using a xenograft mouse model. RESULTS: DSK inhibited cell proliferation, enhanced cell apoptosis, and reduced the cell invasion of MDA-MB-231 and BT549 cells. DSK also reduced the levels of CD206 and CD168 proteins, as well as IL-10 and TGF-β in phorbol 12-myristate 13-acetate-induced THP-1 cells.DSK downregulated the expression of the phosphorylated (p)-PI3K, p-AKT, and p-NF-κB proteins in cells. These effects were reversed by 740 Y-P (PI3K/AKT activator). In addition, DSK significantly reduced the tumor volume and weight in a xenograft mouse model. DSK increased the level of cell apoptosis and decreased the expression of Ki-67 and CD206 in subcutaneous tumor tissue. DSK also inactivated the PI3K/AKT/NF-κB pathway proteins. CONCLUSION DSK inhibits the proliferation, invasion, and tumor immune microenvironment of BC cells by inactivating the PI3K/AKT/NF-κB pathway, indicating that DSK may be a potential therapeutic option for BC treatment.

Background: and Purpose Bilirubin has potent antioxidant, anti-inflammatory, and neuroprotective effects. Herein, we investigated whether total bilirubin (TBIL) modifies the association between hypertension and cerebral small vessel disease (CSVD). Methods: Data were obtained from the PolyvasculaR Evaluation for Cognitive Impairment and vaScular Events study. TBIL and direct bilirubin (DBIL) levels were assayed using fasting venous blood samples. Indirect bilirubin (IBIL) was calculated by subtracting DBIL from TBIL. TBIL was stratified as ≤17 μmol/L and >17 μmol/L based on the biological relevance of Gilbert’s syndrome. Hypertension was defined as blood pressure ≥140/90 mm Hg, self-reported hypertension history, or current use of antihypertensive agents. White matter hyperintensity, lacunes, cerebral microbleeds, and enlarged perivascular spaces were evaluated using magnetic resonance imaging and used to rate CSVD burden according to the criteria proposed by Wardlaw et al. and Rothwell et al. Results: This study included 3,061 participants, with a mean age of 61.2±6.7 years and 46.5% males. After adjusting for confounders, hypertension was associated with increased odds of presence of CSVD (Wardlaw: odds ratio [OR]=1.86, 95% confidence interval [CI] 1.41–2.44, P<0.001; Rothwell: OR=1.84, 95% CI 1.43–2.38, P<0.001) and higher modified total CSVD burden (common OR: 1.85, 95% CI 1.45–2.36, P<0.001) in participants with TBIL ≤17 μmol/L but not in TBIL >17 μmol/L (P for interaction <0.05). Johnson–Neyman analyses showed cut-off concentrations of 22.3–22.4 μmol/L for effect modification by TBIL. IBIL contributed to effect modification, whereas DBIL did not. Conclusions Mildly elevated TBIL may modify the association between hypertension and CSVD.

Aim To study the role and mechanism of ML210 in glioma.Methods The cell viability was detected by CCK8 assay.The percentage of dead cells was detected by SYTOXstaining.The role of ferroptosis-signaling pathway in gliomas was detected bygenomics.Cell proliferation was observed by EdU staining and clone formation assay.Cell migration ability was detec-ted by scratch healing assay.The apoptosis was detec-ted by flow cytometry.Cell mitochondrial function was assesses by JC-1 staining.The mechanism of action of ML210 was detected by molecular docking coupled with immunoblotting assay(Western blot).The levels of ROS,MDA were observed by ELISA.Results Compared with the control group,ML210 treatment dose-dependently decreased glioma cell viability,in-hibited cell proliferation,migration,and increased cell apoptosis and mitochondrial dysfunction,which were reversed by ferroptosis antagonists.Gene microarray screening showed that 688 genes of the ferroptosissig-naling pathway were aberrant and 10 signaling path-ways were altered in gliomas.Molecular docking re-sults showed that ML210 binding to GPX4 significantly inhibited the protein expression level of GPX4 and pro-moted the elevation of ROS and MDA levels.Conclu-sions ML210 produces anti-glioma cells via GPX4-mediated ferroptosis pathway.

Aim To investigate the mechanism of ac-tion of Qingre Zhixue granules in the treatment of IgA vasculitic nephritis(IgAVN)based on network phar-macology and animal experiments.Methods The ac-tive ingredients and targets of Qingre Zhixue granules were screened out by TCMSP database.The disease targets of IgAVN were retrieved by Disgenet,Gene-cards OMIM and TTD databases.The intersection tar-gets were obtained by WeChat online database,and the information was imported into Cytoscope 3.7.1 soft-ware and STRING analysis platform to construct a drug-active component-therapeutic target network.Based on the core targets,GO and KEGG pathway enrichment a-nalysis was performed through the Metascape database to select key targets and core active components.The results of network pharmacology were verified by ani-mal experiments.The animal model of IgAVN was con-structed by the combination of disease and syndrome.The urine red blood cells and 24-hour urine protein of IgAVN model rats after intervention of Qingre Zhixue granules were detected.HE staining and IgA immuno-fluorescence deposition of renal tissue were observed.Western blot and qRT-PCR were used to detect the ex-pression of core targets in renal tissue.Results Net-work pharmacology showed that 109 active ingredients,402 drug targets,1 285 disease targets and 113 inter-section targets were obtained.The core targets screened by protein interaction and network topology a-nalysis were IL6,TNF,VEGFA,etc.The core drug ingredients were quercetin,paeoniflorin,luteolin,kaempferol and baicalein.A total of 2 545 gene func-tions were enriched by GO,and 164 gene pathways were enriched by KEGG.Qingre Zhixue granules could treat IgAVN by regulating TNF signaling pathway,MAPK signaling pathway,IL-17 signaling pathway,HIF-1 signaling pathway,Toll receptor signaling path-way,NF-κB signaling pathway and apoptosis.Animal experiments showed that compared with the blank group,the urine red blood cells and 24-hour urine pro-tein quantification in the model group increased(P＜0.05);the expression of serum IL-6,TNF-α and VEGF-α increased(P＜0.05).HE staining showed glomerular mesangial proliferation,capillary lumen ste-nosis,accompanied by a small amount of inflammatory cell infiltration,glomerular IgA immunofluorescence deposition;the expression of TNF-α,p-p65,p-p38 protein and TNF-α mRNA in renal tissue increased(P＜0.05).After the intervention of Qingre Zhixue gran-ules,urine red blood cells and 24-hour urine protein decreased(P＜0.05).The changes of renal HE stai-ning were improved and glomerular IgA deposition was reduced.TNF-α,p-p65,p-p38 protein and TNF-αmRNA in renal tissue decreased(P＜0.05).Conclu-sions The active ingredients such as quercetin,peony glycoside and luteolin Qingre Zhixue granules regulate TNF signaling pathway,MAPK signaling pathway,IL-17 signaling pathway and reduce IL-6,TNF-α and VEGF-α in the treatment of IgAVN.

Objective::This study aimed to assess the impact of proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor treatment immediately after percutaneous coronary intervention (PCI) on the myocardial salvage index (MSI) in patients with anterior ST-segment elevation myocardial infarction (STEMI) 5-10 d after the procedure.Methods::The early PCSK9 inhibitor thERapy Following pErcutaneous Coronary inTervention (PERFECT) trial is a prospective randomized controlled trial. From January 2021 to December 2023, 32 patients with anterior STEMI from Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Songjiang Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, and Shanghai Tenth People’s Hospital were enrolled in the PERFECT trial. Patients were randomly assigned in a 1∶1 ratio to the PCSK9 inhibitor group ( n = 16) or the control group ( n = 16), and their baseline data were collected. Patients in the PCSK9 inhibitor group (ie, alirocumab group) received a subcutaneous injection of PCSK9 inhibitor (alirocumab, 75 mg) immediately after PCI based on conventional treatment. In the control group, patients received only conventional treatment. The primary endpoint was the MSI measured by cardiovascular magnetic resonance 5-10 d after PCI. The secondary endpoints included the left ventricular ejection fraction measured by cardiovascular magnetic resonance 5-10 d after PCI and the time to peak of creatine kinase isoenzyme-MB and high-sensitivity cardiac troponin T. Safety endpoints included any clinical adverse events that occurred during the 6-month follow-up period. Results::Baseline data during admission showed no intergroup significance. No significant difference in MSI (55.54% ± 14.80% vs. 44.72% ± 15.42%, P = 0.056) and left ventricular ejection fraction (51.24% ± 8.91% vs. 44.99% ± 8.84%, P = 0.060) was observed. Additional, there was no significant difference in the time to peak of creatine kinase isoenzyme-MB ((12.97 ± 5.67) h vs. (14.31 ± 7.04) h, P = 0.557) and high-sensitivity cardiac troponin T ((21.03 ± 12.46) h vs. (21.44 ± 9.99) h, P = 0.920) between the 2 groups. During the 6-month follow-up period, only 1 patient in the PCSK9 inhibitor group developed cerebral hemorrhage 6 months after PCI. Conclusions::Early treatment with alirocumab did not exhibit a significant increase in MSI at 5-10 d in patients with anterior STEMI. Larger trials are necessary to evaluate the impact of early administration of PCSK9 inhibitors after myocardial infarction.

Objective:To explore the predictive efficacy of the HFA-ICOS score for cancer therapy-related cardiac dysfunction (CTRCD) in Chinese patients with breast cancer and lymphoma.Methods:This study was a single-center retrospective cohort study which included patients with breast cancer and lymphoma who were treated with anthracyclines from February 2018 to February 2025 at the First Affiliated Hospital of Dalian Medical University. Patients were evaluated at baseline with cardiac biomarkers and echocardiography, including left ventricular ejection fraction and global longitudinal strain of the left ventricle. After anthracycline therapy, they were followed up at 1, 3, 6, and 12 months. Data involved biomarkers and echocardiography were collected to determine whether CTRCD had occurred. The patients were categorized into low-risk, intermediate-risk, high-risk, and very-high-risk groups using the HFA-ICOS scoring model. The cumulative probability of CTRCD under different HFA-ICOS risk stratification was analyzed using Kaplan-Meier survival curves. The effect of HFA-ICOS risk stratification on CTRCD was assessed using an univariate Cox proportional hazards regression model. The predictive efficacy of the HFA-ICOS model and its utility in clinical decision-making were assessed with receiver operating characteristic (ROC) curves, calibration curves, and decision curves at each time point.Results:A total of 286 patients, aged 55 (44, 61) years, were enrolled, of whom 33 (11.5%) cases were male. And 113 (39.5%) patients developed CTRCD during a median follow-up time of 111 (70, 210) days. HFA-ICOS risk stratification showed that 228 (79.7%) were low-risk, 49 (17.1%) were intermediate-risk, and a total of 9 (3.1%) were high-risk and very high-risk. The difference in the occurrence of CTRCD over time between patients with different HFA-ICOS risk stratification was statistically significant ( Plog-rank<0.001). Cox proportional regression hazards analysis showed an increased risk of CTRCD development in intermediate-risk ( HR=1.95, 95% CI 1.22-3.00, P=0.006) and high-risk and very high-risk patients ( HR=4.12, 95% CI 1.66-8.54, P=0.004) compared with low-risk patients. The ROC curves showed that the area under the curve of the HFA-ICOS model predicting CTRCD was 0.532, 0.597, 0.600 and 0.577 at 1, 3, 6 and 12 months, respectively. The calibration curves indicated Brier scores of 0.041 (95% CI 0.013-0.067), 0.144 (95% CI 0.115-0.173), 0.232 (95% CI 0.215-0.249) and 0.236 (95% CI 0.220-0.251) at 1, 3, 6 and 12 months, correspondingly. The clinical decision curve suggested that clinical intervention may have a net benefit when the risk threshold is between 0.15 and 0.18 at 1 month, between 0.10 and 0.50 at 3 months, and between 0.30 and 0.70 at 6 and 12 months. Conclusion:The HFA-ICOS score could predict the occurrence of CTRCD in patients with breast cancer and lymphoma treated with anthracycline drugs, although its predictive efficacy is limited, and the prediction model requires further validation in a larger population.

Objective To analyze the expression of monocyte surface antigen-presenting factors CD86+and HLA-DR in the subacute phase of burn injury,and the molecular mechanism of monocytes contributing to persistent inflammation.Methods The mice were divided into the sham group and the burn group,and a mouse model of 30％body surface burn was estab-lished.Spleens were collected from mice on the 8th day after burn injury,and monocytes were isolated for transcriptomic analy-sis.A mouse model of Notch1 lentiviral transfection was constructed,and models of sham burn+blank control(sham-NC),burn+blank control(burn-NC),sham burn+Notch1 shRNA(sham-sh),and burn+Notch1 shRNA(burn-sh)were estab-lished.The qRT-PCR and Western blot were used to detect the expressions of monocyte surface antigens CD86+and HLA-DR.Immunofluorescence was performed to analyze the expression of CD86+and HLA-DR in splenic monocytes.ELISA was used to analyze serum levels of IL-10 and CRP.Results On the 8th day after burn injury,compared with the sham burn group,the expressions of monocyte surface antigens CD86+and HLA-DR were decreased,while serum levels of IL-10 and CRP were increased in the burn group.Contents of IL-10 and CRP showed significant negative correlations with CD86+and HLA-DR,re-spectively.Transcriptomic analysis revealed 258 significantly upregulated genes and 360 significantly downregulated genes in splenic monocytes from the burn group.The differentially expressed genes primarily enriched in the Notch signaling path-way.Western blot results showed a significant upregulation of Notch1 expression.After lentiviral inhibition of Notch1 signaling invivo,compared with the burn-NC group,expressions of CD86+and HLA-DR on monocyte surfaces were increased,and ser-um levels of IL-10 and CRP were decreased in the burn-sh group.Conclusion The functional inhibition of splenic monocytes is mediated by Notch1 signaling pathway in the subacute phase of burn injury.Inhibition of Notch1 signaling in vivo improves the antigen-presenting capacity of monocytes after burn injury and inhibits the secretion of inflammatory factors.

Objective·To investigate the causal relationship between plasma zinc-alpha-2-glycoprotein 1(AZGP1)and heart failure(HF)by using Mendelian randomization(MR)analysis and experimental validation.Methods·A two-sample MR analysis was performed to assess the causal relationship between AZGP1 and HF by integrating large-scale genome-wide association study(GWAS)data on plasma proteins and HF.The inverse-variance weighted(IVW)method was employed as the primary analytical approach,supplemented by MR-Egger regression,weighted median,and simple median methods.Horizontal pleiotropy was tested by using MR-PRESSO global test and MR-Egger intercept analysis.Colocalization analysis was conducted to validate genetic locus overlap.Additionally,a clinical cohort(84 HF patients and 68 healthy controls)was analyzed,with plasma AZGP1 levels quantified by enzyme-linked immunosorbent assay(ELISA).Results·MR analysis showed that elevated plasma AZGP1 levels were significantly associated with reduced HF risk(OR=0.82,95%CI 0.75?0.90,P=1.70×10-5).Colocalization analysis confirmed that AZGP1 expression and HF shared causal genetic variants(posterior probability for H4=0.69).Sensitivity and reverse MR analyses supported the robustness of the results.ELISA confirmed that plasma AZGP1 levels were significantly lower in HF patients compared to healthy controls,reinforcing its protective role in HF.Conclusion·This study demonstrates AZGP1 exerts a protective causal effect on HF and may serve as a potential biomarker for HF treatment.