Background Neck-related work-related musculoskeletal disorders (WMSDs) are a major type of musculoskeletal disorders with a relatively high proportion. Shanghai has a large number of occupational populations; however, the occurrence of WMSDs at neck among the occupational populations across industries in this city has not been reported, and needs to be addressed. Objective To understand the occurrence of neck-related WMSDs and their influencing factors among occupational populations in 8 industries in Shanghai, and to provide a scientific basis for the prevention and control of WMSDs in this population. Methods From February 2024 to February 2025, a cross-sectional survey employed stratified cluster sampling to select 7829 employed workers from 48 enterprises across 8 industries in Shanghai. The study investigated the occurrence of neck-related WMSDs among the participants over the preceding 12 months. Logistic regression analysis was employed to examine the relationships between WMSDs and various occupational factors. Results A total of 7770 questionnaires were collected, yielding an effective response rate of 99.2%. Overall, the positive rate of neck-related WMSDs among the participants was 11.89% (924/7770). Among different industries, the environmental sanitation industry (19.48%), pharmaceutical manufacturing industry (14.57%), and cigarette manufacturing industry (13.66%) had higher prevalence of neck-related WMSDs. Univariate analysis showed that the risk of neck-related WMSDs was higher in the following groups: those with a job tenure ≥5 years in the current position (OR=1.50–1.70), females (OR=1.77), those with higher education levels (master’s degree or above, OR=2.27), and those with worse self-rated health (very poor health, OR=4.38) (P＜0.05). Multivariate logistic regression analysis identified the following independent risk factors for neck WMSDs: environmental sanitation industry (OR=7.30, 95%CI: 4.72, 11.87), higher educational attainment (master’s degree or above: OR=2.16, 95%CI: 1.36, 3.35), worse self-rated health status (very poor: OR=1.95, 95%CI: 1.31, 2.85), work performed in a single workshop (OR=1.36, 95%CI: 1.13, 1.64), understaffing (OR=1.46, 95%CI: 1.25, 1.70), slight neck forward flexion (OR=1.64, 95%CI: 1.32, 2.06), severe neck forward flexion (OR=2.55, 95%CI: 1.97, 3.30), and maintaining a fixed neck posture for a prolonged period (OR=2.28, 95%CI: 1.93, 2.70). Conversely, work rotation (OR=0.75, 95%CI: 0.65, 0.87), adequate rest (OR=0.70, 95%CI: 0.60, 0.82), and severe back flexion (OR=0.63, 95%CI: 0.46, 0.85) were protective factors against neck-related WMSDs. For the nomogram, the area under the curve (AUC)=0.75 (95%CI: 0.74, 0.77), Hosmer-Lemeshow test P=0.764, and Brier score=0.094, indicating that the model had good discrimination and calibration. Conclusion Among the occupational populations in Shanghai, the environmental sanitation industry, pharmaceutical manufacturing industry, and cigarette manufacturing industry are identified as high-risk industries for neck-related WMSDs. Industry affiliation, educational level, work organization patterns, and awkward neck working postures are confirmed as the core influencing factors for the development of neck-related WMSDs. Targeted and comprehensive intervention measures should be formulated focusing on the aforementioned high-risk industries and key influencing factors. Multi-dimensional collaborative efforts, including ergonomic optimization, improvement of labor management systems, and strengthened health education and promotion, should be implemented to effectively control the risk of neck-related WMSDs in the occupational population, and to provide robust statistical evidence for the advancement of regional occupational health prevention and control strategies.

ObjectiveTo explore the key genes influencing diacylglycerol metabolism in neuroblastoma （NB）， clarify the expression and clinical significance of diacylglycerol acyltransferase 2 （DGAT2） in NB， and provide a theoretical basis for the diagnosis and targeted therapy of NB. MethodsNB transcriptome data were obtained from GEO （GSE49710） and TCGA （TARGET-NBL） databases. Differentially expressed genes （DEGs） commonly upregulated in MYCN-amplified groups were screened， and the key gene DGAT2 was identified by intersecting the screened DEGs with the diacylglycerol metabolism-related gene set followed by prognostic analysis and comparison. The expression of DGAT2 was analyzed via the R2 database. The potential impact of DGAT2 on the immune microenvironment was explored by combining the single-cell dataset GSE137804. Immunohistochemistry （IHC） was used to detect the expression level of DGAT2 and its correlation with MYCN expression in 55 clinical NB tissues and mouse xenograft tumor tissues. ResultsA total of 907 DEGs commonly upregulated in the MYCN-amplified groups were screened， among which three DEGs were highly expressed in the diacylglycerol metabolism-related gene set （P＜0.05）. After comparison， DGAT2 was found to have the most significant impact on prognosis （HR=1.4， 95% CI：1.2，1.7； P=5.41×10^-7）. Survival analysis showed that patients with high DGAT2 expression had a significantly shorter overall survival. Single-cell analysis revealed that high expression of DGAT2 led to an immunosuppressive microenvironment in NB. IHC results showed that the expression of DGAT2 in NB tissues was significantly positively correlated with MYCN expression in the tumor tissue microarrays of clinical NB patients and the tissues of mouse ectopic xenograft tumors （r_s=0.369 4，P＜0.01）. ConclusionsDGAT2 is highly expressed in MYCN-amplified NB， and may independently predict poor prognosis in NB patients. It is expected to become a diagnostic marker for NB and a potential therapeutic target for MYCN-amplified NB.

ObjectiveTo interpret the main contents of the Expert Consensus on Clinical Application of Yifei Zhike Capsules （hereinafter referred to as the Consensus）， analyze its evidence basis， and explore future research directions， thus providing a reference for rational drug use in clinical practice. MethodsThe core contents of the Consensus are summarized. Focusing on clinical issues， this paper summarizes the recommendations and consensus suggestions in the Consensus and explains them from aspects such as indications， key advantages， usage and dosage， combined medication， contraindications， precautions， and safety. ResultsThe Consensus clearly states that Yifei Zhike capsules can be used for acute or chronic bronchitis， pulmonary tuberculosis and other respiratory system diseases. It for the first time proposes that the applicable TCM syndrome of Yifei Zhike capsules is Qi-Yin deficiency together with combined phlegm and stasis. For different diseases， the Consensus provides specific usage instructions， dosage， and treatment course recommendations， supplementing the contents not covered in the drug instructions. In terms of combined medication， the Consensus emphasizes the principle of using this drug in combination with standardized chemotherapy regimens or conventional Western medicines and the applicability for the treatment of pulmonary tuberculosis and moderate to severe acute or chronic bronchitis. In terms of safety， the Consensus proposes methods for identifying common adverse reactions， drug contraindications， and precautions based on a review of the existing data and preliminarily builds a risk management framework. However， the evidence on which the Consensus is based are mostly early studies， with small sample sizes， which result in the low evidence grades （mainly C and D） of some recommendations. ConclusionThe Consensus provides specific guidance for the clinical use of Yifei Zhike capsules. However， due to the limited quality of the existing research evidence， more high-quality clinical studies are needed in the future to further verify its efficacy， safety， and explore its broader application prospects.

ObjectiveTo explore the protective effect and underlying mechanism of Gegen Qinliantang on cognitive function in db/db mice with diabetic cognitive impairment （DCI）. MethodsThirty-two 8-week-old male db/db mice were randomly assigned to the model group， dapagliflozin group （1.0 mg·kg^-1·d^-1）， low-dose Gegen Qinliantang group （6.24 g·kg^-1·d^-1）， and high-dose Gegen Qinliantang group （24.96 g·kg^-1·d^-1）. Eight db/m mice served as the normal group. All mice were administered the corresponding treatment once daily by gavage for 10 consecutive weeks. Body weight and fasting blood glucose （FBG） were dynamically monitored. The Morris water maze test was used to evaluate cognitive function. Hematoxylin-eosin （HE） staining and Nissl staining were used to observe pathological changes in the hippocampus. Enzyme-linked immunosorbent assay （ELISA） was employed to measure the levels of tumor necrosis factor-α （TNF-α） and interleukin-1β （IL-1β） in hippocampal tissue. Immunofluorescence double staining was used to detect the co-expression of M1 microglial marker CD16/32 and ionized calcium-binding adapter molecule 1 （IBA1） in the hippocampus. Western blot analysis was performed to detect the protein expression of postsynaptic density protein 95 （PSD-95）， synapsin （SYN）， nuclear factor-κB p65 （NF-κB p65）， and phosphorylated NF-κB p65 （p-NF-κB p65） in the hippocampus. ResultsCompared with the normal group， the model group showed significantly increased body weight and FBG levels （P<0.01）， significantly prolonged escape latency and reduced platform crossings in the Morris water maze test （P<0.01）， disordered arrangement of hippocampal neurons， nuclear pyknosis， increased neuronal necrosis， reduced Nissl bodies， decreased expression of synaptic proteins PSD-95 and SYN （P<0.01）， increased CD16/32⁺ /IBA1⁺ positive rate， elevated levels of TNF-α and IL-1β， and an increased p-NF-κB p65/NF-κB p65 ratio （P<0.01）. Compared with the model group， the dapagliflozin group exhibited significantly reduced FBG levels at weeks 5 and 10 （P<0.05， P<0.01） and increased body weight. The high-dose Gegen Qinliantang group showed significantly reduced FBG at week 10 （P<0.05）. Escape latency was significantly reduced on days 3 and 5 of the water maze test in the dapagliflozin group and on day 5 in the high-dose Gegen Qinliantang group （P<0.05）. Platform crossings were significantly increased in both the dapagliflozin group and the high-dose Gegen Qinliantang group （P<0.05）. Hippocampal pathological damage was alleviated to varying degrees in the dapagliflozin group and the low- and high-dose Gegen Qinliantang groups， with significantly increased expression of PSD-95 and SYN （P<0.01）. Further studies revealed that both low- and high-dose Gegen Qinliantang reduced hippocampal IL-1β levels and the CD16/32⁺/IBA1⁺ positive rate of microglia， while the high-dose group also significantly reduced hippocampal TNF-α levels and the p-NF-κB p65/NF-κB p65 （P<0.05， P<0.01）. ConclusionGegen Qinliantang can improve hyperglycemia， cognitive dysfunction， and synaptic damage in DCI， inhibit M1 polarization of microglia and neuroinflammation， and its mechanism may be related to the inhibition of NF-κB activation.

ObjectiveTo explore the protective effect and underlying mechanism of Gegen Qinliantang on cognitive function in db/db mice with diabetic cognitive impairment （DCI）. MethodsThirty-two 8-week-old male db/db mice were randomly assigned to the model group， dapagliflozin group （1.0 mg·kg^-1·d^-1）， low-dose Gegen Qinliantang group （6.24 g·kg^-1·d^-1）， and high-dose Gegen Qinliantang group （24.96 g·kg^-1·d^-1）. Eight db/m mice served as the normal group. All mice were administered the corresponding treatment once daily by gavage for 10 consecutive weeks. Body weight and fasting blood glucose （FBG） were dynamically monitored. The Morris water maze test was used to evaluate cognitive function. Hematoxylin-eosin （HE） staining and Nissl staining were used to observe pathological changes in the hippocampus. Enzyme-linked immunosorbent assay （ELISA） was employed to measure the levels of tumor necrosis factor-α （TNF-α） and interleukin-1β （IL-1β） in hippocampal tissue. Immunofluorescence double staining was used to detect the co-expression of M1 microglial marker CD16/32 and ionized calcium-binding adapter molecule 1 （IBA1） in the hippocampus. Western blot analysis was performed to detect the protein expression of postsynaptic density protein 95 （PSD-95）， synapsin （SYN）， nuclear factor-κB p65 （NF-κB p65）， and phosphorylated NF-κB p65 （p-NF-κB p65） in the hippocampus. ResultsCompared with the normal group， the model group showed significantly increased body weight and FBG levels （P<0.01）， significantly prolonged escape latency and reduced platform crossings in the Morris water maze test （P<0.01）， disordered arrangement of hippocampal neurons， nuclear pyknosis， increased neuronal necrosis， reduced Nissl bodies， decreased expression of synaptic proteins PSD-95 and SYN （P<0.01）， increased CD16/32⁺ /IBA1⁺ positive rate， elevated levels of TNF-α and IL-1β， and an increased p-NF-κB p65/NF-κB p65 ratio （P<0.01）. Compared with the model group， the dapagliflozin group exhibited significantly reduced FBG levels at weeks 5 and 10 （P<0.05， P<0.01） and increased body weight. The high-dose Gegen Qinliantang group showed significantly reduced FBG at week 10 （P<0.05）. Escape latency was significantly reduced on days 3 and 5 of the water maze test in the dapagliflozin group and on day 5 in the high-dose Gegen Qinliantang group （P<0.05）. Platform crossings were significantly increased in both the dapagliflozin group and the high-dose Gegen Qinliantang group （P<0.05）. Hippocampal pathological damage was alleviated to varying degrees in the dapagliflozin group and the low- and high-dose Gegen Qinliantang groups， with significantly increased expression of PSD-95 and SYN （P<0.01）. Further studies revealed that both low- and high-dose Gegen Qinliantang reduced hippocampal IL-1β levels and the CD16/32⁺/IBA1⁺ positive rate of microglia， while the high-dose group also significantly reduced hippocampal TNF-α levels and the p-NF-κB p65/NF-κB p65 （P<0.05， P<0.01）. ConclusionGegen Qinliantang can improve hyperglycemia， cognitive dysfunction， and synaptic damage in DCI， inhibit M1 polarization of microglia and neuroinflammation， and its mechanism may be related to the inhibition of NF-κB activation.

Iron overload is strongly associated with heart disease. Ferroptosis is a new form of regulated cell death indicated in cardiac ischemia-reperfusion (I/R) injury. However, the specific molecular mechanism of myocardial injury caused by iron overload in the heart is still unclear, and the involvement of ferroptosis in iron overload-induced myocardial injury is not fully understood. In this study, we observed that ferroptosis participated in developing of iron overload and I/R-induced cardiomyopathy. Mechanistically, we discovered that Parkin inhibited iron overload-induced ferroptosis in cardiomyocytes by promoting the ubiquitination of long-chain acyl-CoA synthetase 4 (ACSL4), a crucial protein involved in ferroptosis-related lipid metabolism pathways. Additionally, we identified p53 as a transcription factor that transcriptionally suppressed Parkin expression in iron-overloaded cardiomyocytes, thereby regulating iron overload-induced ferroptosis. In animal studies, cardiac-specific Parkin knockout mice (Myh6-CreER ^T2 /Parkin ^fl/fl ) fed a high-iron diet presented more severe myocardial damage, and the high iron levels exacerbated myocardial I/R injury. However, the ferroptosis inhibitor Fer-1 significantly suppressed iron overload-induced ferroptosis and myocardial I/R injury. Moreover, Parkin effectively protected against impaired mitochondrial function and prevented iron overload-induced mitochondrial lipid peroxidation. These findings unveil a novel regulatory pathway involving p53-Parkin-ACSL4 in heart disease by inhibiting of ferroptosis.

Perimenopause raises the risk and incidence of depression, whereas the underlying molecular mechanism remains unclear. Disturbed glucose regulation has been widely documented in depressive disorders, which renders the brain susceptible to various stresses such as estrogen depletion. However, whether and how glucose dysfunction regulates depression-like behaviors and neuronal damage in perimenopausal transition remains unexplored. Here, a prominent depressive phenotype was found in perimenopausal mice induced by the ovarian toxin 4-vinylcyclohexene diepoxide (VCD). The VCD depression susceptible group (VCD^SS) and the VCD depression resilient group (VCD^RES) were determined using a ROC-based behavioral screening approach. We found that the hippocampus, a crucial region linked to depression, had hyperglycemia and mitochondrial abnormalities. Interestingly, oral administration of the SGLT2 inhibitor empagliflozin (EMPA) and intrahippocampal glucose infusion suggest a close relationship between hyperglycemia in the hippocampus and the susceptibility to depression. We verified that cytochrome c oxidase 7c (COX7C) downregulation is a potential cause of the high glucose-induced neuronal injury using proteomic screening and biochemical validations. High glucose causes COX7C to be ubiquitinated in a S-phase kinase associated protein 1 (SKP1)-dependent manner. According to these results, SKP1/COX7C represents a unique therapeutic target and a novel molecular route for treating perimenopausal depression.

Ovarian cancer is the most lethal malignancy affecting the female reproductive system. Pharmacological inhibitors targeting CDK4/6 have demonstrated promising efficacy across various cancer types. However, their clinical benefits in ovarian cancer patients fall short of expectations, with only a subset of patients experiencing these advantageous effects. This study aims to provide further clinical and biological evidence for antineoplastic effects of a CDK4/6 inhibitor (TQB4616) in ovarian cancer and explore underlying mechanisms involved. Patient-derived ovarian cancer organoid models were established to evaluate the effectiveness of TQB3616. Potential key genes related to TQB3616 sensitivity were identified through RNA-seq analysis, and TRIM4 was selected as a candidate gene for further investigation. Subsequently, co-immunoprecipitation and GST pull-down assays confirmed that TRIM4 binds to hnRNPDL and promotes its ubiquitination through RING and B-box domains. RIP assay demonstrated that hnRNPDL binded to CDKN2C isoform 2 and suppressed its expression by alternative splicing. Finally, in vivo studies confirmed that the addition of siTRIM4 significantly improved the effectiveness of TQB3616. Overall, our findings suggest that TRIM4 modulates ubiquitin-mediated degradation of hnRNPDL and weakens sensitivity to CDK4/6 inhibitors in ovarian cancer treatment. TRIM4 may serve as a valuable biomarker for predicting sensitivity to CDK4/6 inhibitors in ovarian cancer.
Humans ; Female ; Ovarian Neoplasms/pathology* ; Animals ; Tripartite Motif Proteins/genetics* ; Mice ; Cyclin-Dependent Kinase 4/antagonists & inhibitors* ; Cell Line, Tumor ; Cyclin-Dependent Kinase 6/antagonists & inhibitors* ; Protein Kinase Inhibitors/pharmacology* ; Ubiquitin/metabolism* ; Xenograft Model Antitumor Assays ; Ubiquitination ; Antineoplastic Agents/pharmacology*

Objective: To analyze the disease burden of chronic obstructive pulmonary disease (COPD) and changes in its risk factors among residents in Zhejiang Province from 1990 to 2021, so as to identify key priorities for COPD prevention and control. Methods: Data on COPD mortality and disability-adjusted life years (DALY) for residents in Zhejiang Province from 1990 to 2021 were collected from the Global Burden of Disease (GBD) 2021 database. Standardized mortality and standardized DALY rate were calculated using the GBD 2021 world population standard structure. Premature mortality was computed via the life table method. The average annual percent change (AAPC) was applied to analyze trends in COPD mortality, DALY rate, and premature mortality. Changes in deaths of COPD risk factors were evaluated using population attributable fraction (PAF). Results: From 1990 to 2021, the standardized COPD mortality in Zhejiang Province decreased from 272.40/100 000 to 70.56/100 000 (AAPC=-4.395%), and the standardized DALY rate declined from 4 167.37/100 000 to 1 071.89/100 000 (AAPC=-4.396%). Similar downward trends were observed in both males (AAPC=-3.933%, -4.173%) and females (AAPC=-4.785%, -4.480%), all P<0.05. Crude mortality and DALY rates increased with age, and the crude mortality and DALY rates of various age groups in Zhejiang Province showed decreasing trends from 1990 to 2021 (all P<0.05). The premature mortality declined from 4.37% to 0.60% from 1990 to 2021 (AAPC=- 6.206%), with consistent trends across males and females (AAPC=- 6.144%, - 6.379%, all P<0.05). From 1990 to 2021, particulate matter pollution showed the largest reduction in PAF (- 56.76%), while ambient ozone pollution had the largest increase (103.07%) in Zhejiang Province. By 2021, smoking became the leading risk factor for deaths of COPD (PAF=43.32%). Conclusions The standardized mortality, standardized DALY rate, and premature mortality for COPD show consistent declining trends in Zhejiang Province from 1990 to 2021. However, risk factors such as smoking and ambient ozone pollution require intensified focus to further reduce disease burden of COPD.

Objective To analyze the expression differences in immune cells and cytokines in advanced ovarian cancer with different homologous recombination deficiency(HRD)statuses,and provide insights for novel therapeutic strategies.Methods A total of 68 patients with International Federation of Gynecology and Obstetrics(FIGO)stageⅢ-Ⅳ epithelial ovarian cancer,who were treated at Department of Obstetrics and Gynecology,Ruijin Hospital,Shanghai Jiao Tong University School of Medicine from Jan.2018 to Jan.2023,were enrolled.Based on genetic testing results,patients were stratified into HRD-positive(n=30)and HRD-negative(n=38)groups.Baseline characteristics and clinical outcomes were compared.The expression levels of CD4,CD8 and CD25 in ovarian cancer tissues of the 2 groups were analyzed by immunohistochemical staining.The proportions of CD4+T cells,CD8+T cells,and CD4+CD25+regulatory T cells(Treg cells)and CD4+/CD8+ratio in blood were analyzed by flow cytometry.The serum levels of interferon-γ(IFN-γ),interleukin(IL)-2,IL-6 and IL-10 were detected by enzyme-linked immunosorbent assay.Results There were no significant differences in age,course of disease,family history,initial treatment,tumor FIGO stage,or tumor differentiation degree between the HRD-positive group and HRD-negative group(all P＞0.05).In terms of clinical efficacy,the objective remission rate and disease control rate of patients in the HRD-positive group were significantly higher than those in the HRD-negative group(both P＜0.05).Compared with the HRD-negative group,the expression levels of CD4,CD8,and CD25 in tumor tissues of patients were all increased in the HRD-positive group(all P＜0.05),the proportions of CD4+T cells,CD8+T cells,and CD4+CD25+Treg cells in blood were all increased(all P＜0.05),the CD4+/CD8+ratio in blood was increased(P＜0.05),the serum levels of IL-2,IL-6,and IL-10 were all increased(all P＜0.05),while the serum level of IFN-γ had no significant difference between the 2 groups(P＞0.05).Conclusion HRD-positive ovarian cancer displays enhanced tumor-infiltrating lymphocytes and immunomodulatory cytokine secretion compared to HRD-negative cases,suggesting greater sensitivity to immunotherapy and better prognosis.