Background Due to the unique working environment and numerous occupational disease hazards, workers in mining industry are particularly susceptible to psychological problems such as occupational stress. Objective To understand the current status of occupational stress, depressive symptoms, anxiety symptoms and sleep quality of workers in ferrous and non-ferrous metal mining industry in Gansu Province, and to explore the effects of occupational stress on depressive symptoms, anxiety symptoms, and sleep. Methods From April to December 2022, the workers of 25 large, medium, and small and micro enterprises were selected by stratified cluster random sampling and surveyed in ferrous and non-ferrous metal mining industry in Gansu Province. The Occupational Health Literacy Questionnaire of National Key Population, Core Occupational Stress Scale, Patient Health Questionnaire-q, Generalized Anxiety Disorder, and Self-administer Sleep Questionnaire were used to collect basic information, occupational stress, depressive symptoms, anxiety symptoms, and sleep quality of the workers. Chi-square test was used to compare occupational stress, depressive symptoms, anxiety symptoms and sleep disorders among different categories. Logistic regression model was used to study the effects of occupational stress on depressive symptoms, anxiety symptoms, and sleep quality. Results In this study, 2192 workers in mining industry were surveyed, of which 2087 returned valid questionnaires, and the recovery rate of valid questionnaires was 95.2%. Among them, 728 (38.4%) reported occupational stress. There were statistically significant differences in the positive rate of occupational stress among workers by gender, age, marital status, education level, average monthly income, length of service, enterprise size, and night shifts (P<0.001). The positive rates of depressive symptoms, anxiety symptoms, and sleep disorders in the mining industry workers were 85.6%, 49.8%, and 47.3%, respectively. The positive rates of depressive symptoms, anxiety symptoms, and sleep disorders among workers with higher occupational stress were higher than those among workers without occupational stress (P<0.001). The logistic regression analysis showed that occupational stress was a common risk factor for depressive symptoms (OR=3.29, 95%CI: 2.26, 4.79), anxiety symptoms (OR=2.87, 95%CI: 2.33, 3.53), and sleep disorder (OR=1.78, 95%CI: 1.46, 2.16). In addition, length of service and enterprise-scale were also risk factors for depressive symptoms, anxiety symptoms, and sleep disorders. In the 5−<10 and 10−<20 years of service groups, the risks of reporting depressive symptoms were 1.80 (95%CI: 1.18, 2.74) and 1.73 (95%CI: 1.10, 2.71) times higher than that of workers with less than 1 year of service, respectively; the risks of reporting anxiety symptoms were 1.98 (95%CI: 1.42, 2.76) and 2.11 (95%CI: 1.48, 3.01) times higher than that with less than 1 year of service, respectively; the risks of reporting sleep disorders were 1.58 (95%CI: 1.15, 2.16) and 1.78 (95%CI: 1.29, 2.45) times higher than that with less than 1 year of service, respectively. Workers in large enterprises were inclined to report more depressive symptoms, anxiety symptoms, and sleep disturbances than those in micro and small enterprises (OR=3.53, 95%CI: 2.41, 5.16; OR=2.49, 95%CI: 1.98, 3.13; OR=2.10, 95%CI: 1.67, 2.62). Conclusion The occupational stress level of mining industry workers in Gansu Province is high, and reporting occupational stress, 5−<10 and 10−<20 working age groups, and large enterprises are important risk factors affecting workers' mental health and sleep. It is necessary to increase the attention and develop intervention programs for mental health of miners in the working age group of 5−20 years old and in large enterprises.

ObjectiveTo investigate the mechanism by which 2，3，5，4'-tetrahydroxyldiphenylethylene-2-O-glucoside （THSG） mitigates cerebral ischemia/reperfusion （CI/R） injury by regulating mitochondrial calcium overload and promoting mitophagy. MethodsSixty male SD rats were randomized into sham， model， SAS （40 mg·kg^-1）， and low-， medium- and high-dose （10， 20， 40 mg·kg^-1， respectively） THSG groups， with 10 rats in each group. The middle cerebral artery occlusion/reperfusion （MCAO/R） model was established by the modified Longa suture method. An oxygen-glucose deprivation/reoxygenation （OGD/R） model was constructed in PC12 cells. Neurological deficits were assessed via Zea Longa scoring， and cerebral infarct volume was measured by 2，3，5-triphenyltetrazolium chloride （TTC） staining. Structural and functional changes of cortical neurons in MCAO/R rats were assessed by hematoxylin-eosin and Nissl staining. PC12 cell viability was detected by cell counting kit-8 （CCK-8） assay， and mitochondrial calcium levels were quantified by Rhod-2 AM. Immunofluorescence was used to detect co-localization of PTEN-induced kinase 1 （PINK1） and leucine zipper/EF-hand-containing transmembrane protein 1 （LETM1） in neurons. Transmission electron microscopy （TEM） was employed to observe mitochondrial morphology in neurons. Western blot was employed to analyze the expression of translocase of outer mitochondrial membrane 20 （TOMM20）， autophagy-associated protein p62， microtubule-associated protein light chain 3 （LC3）， cysteinyl aspartate-specific proteinase-9 （Caspase-9）， B-cell lymphoma 2-associated protein X （Bax）， and cytochrome C （Cyt C）. ResultsCompared with the sham group， the model group exhibited increased infarct volume （P<0.01） and neurological deficit scores （P<0.01）， neuronal structure was disrupted with reduced Nissl bodies. （P<0.01）， mitochondrial swelling/fragmentation， decreased PINK1/LETM1 co-localization （P<0.01）， upregulated protein levels of LC3Ⅱ/LC3Ⅰ， TOMM20， Caspase-9， Bax， and Cyt C （P<0.01）， downregulated protein level of p62 （P<0.05）， weakened PC12 viability （P<0.01）， and elevated mitochondrial calcium level （P<0.01）. Compared with the model group， THSG and SAS groups showed reduced infarct volumes （P<0.05，P<0.01） and neurological deficit scores （P<0.05，P<0.01）， mitigated mitochondrial damage， and increased PINK1/LETM1 co-localization （P<0.01）. Medium/high-dose THSG and SAS alleviated the neurological damage， increased Nissl bodies （P<0.05，P<0.01）， downregulated the protein levels of p62， TOMM20， Caspase-9， Bax， and Cyt C （P<0.05，P<0.01）， and elevated the LC3Ⅱ/LC3Ⅰ level （P<0.05，P<0.01）. High-dose THSG enhanced PC12 cell viability （P<0.01）， increased PINK1/LETM1 co-localization （P<0.01）， and reduced mitochondrial calcium （P<0.01）. ConclusionTHSG may exert the neuroprotective effect on CI/R injury by activating the PINK1-LETM1 signaling pathway， reducing the mitochondrial calcium overload， and promoting mitophagy.

ObjectiveTo investigate the mechanism by which 2，3，5，4'-tetrahydroxyldiphenylethylene-2-O-glucoside （THSG） mitigates cerebral ischemia/reperfusion （CI/R） injury by regulating mitochondrial calcium overload and promoting mitophagy. MethodsSixty male SD rats were randomized into sham， model， SAS （40 mg·kg^-1）， and low-， medium- and high-dose （10， 20， 40 mg·kg^-1， respectively） THSG groups， with 10 rats in each group. The middle cerebral artery occlusion/reperfusion （MCAO/R） model was established by the modified Longa suture method. An oxygen-glucose deprivation/reoxygenation （OGD/R） model was constructed in PC12 cells. Neurological deficits were assessed via Zea Longa scoring， and cerebral infarct volume was measured by 2，3，5-triphenyltetrazolium chloride （TTC） staining. Structural and functional changes of cortical neurons in MCAO/R rats were assessed by hematoxylin-eosin and Nissl staining. PC12 cell viability was detected by cell counting kit-8 （CCK-8） assay， and mitochondrial calcium levels were quantified by Rhod-2 AM. Immunofluorescence was used to detect co-localization of PTEN-induced kinase 1 （PINK1） and leucine zipper/EF-hand-containing transmembrane protein 1 （LETM1） in neurons. Transmission electron microscopy （TEM） was employed to observe mitochondrial morphology in neurons. Western blot was employed to analyze the expression of translocase of outer mitochondrial membrane 20 （TOMM20）， autophagy-associated protein p62， microtubule-associated protein light chain 3 （LC3）， cysteinyl aspartate-specific proteinase-9 （Caspase-9）， B-cell lymphoma 2-associated protein X （Bax）， and cytochrome C （Cyt C）. ResultsCompared with the sham group， the model group exhibited increased infarct volume （P<0.01） and neurological deficit scores （P<0.01）， neuronal structure was disrupted with reduced Nissl bodies. （P<0.01）， mitochondrial swelling/fragmentation， decreased PINK1/LETM1 co-localization （P<0.01）， upregulated protein levels of LC3Ⅱ/LC3Ⅰ， TOMM20， Caspase-9， Bax， and Cyt C （P<0.01）， downregulated protein level of p62 （P<0.05）， weakened PC12 viability （P<0.01）， and elevated mitochondrial calcium level （P<0.01）. Compared with the model group， THSG and SAS groups showed reduced infarct volumes （P<0.05，P<0.01） and neurological deficit scores （P<0.05，P<0.01）， mitigated mitochondrial damage， and increased PINK1/LETM1 co-localization （P<0.01）. Medium/high-dose THSG and SAS alleviated the neurological damage， increased Nissl bodies （P<0.05，P<0.01）， downregulated the protein levels of p62， TOMM20， Caspase-9， Bax， and Cyt C （P<0.05，P<0.01）， and elevated the LC3Ⅱ/LC3Ⅰ level （P<0.05，P<0.01）. High-dose THSG enhanced PC12 cell viability （P<0.01）， increased PINK1/LETM1 co-localization （P<0.01）， and reduced mitochondrial calcium （P<0.01）. ConclusionTHSG may exert the neuroprotective effect on CI/R injury by activating the PINK1-LETM1 signaling pathway， reducing the mitochondrial calcium overload， and promoting mitophagy.

Idiopathic pulmonary fibrosis (IPF), a chronic interstitial lung disease, is characterized by aberrant wound healing, excessive scarring and the formation of myofibroblastic foci. Although the role of alternative splicing (AS) in the pathogenesis of organ fibrosis has garnered increasing attention, its specific contribution to pulmonary fibrosis remains incompletely understood. In this study, we identified an up-regulation of serine/arginine-rich splicing factor 7 (SRSF7) in lung fibroblasts derived from IPF patients and a bleomycin (BLM)-induced mouse model, and further characterized its functional role in both human fetal lung fibroblasts and mice. We demonstrated that enhanced expression of Srsf7 in mice spontaneously induced alveolar collagen accumulation. Mechanistically, we investigated alternative splicing events and revealed that SRSF7 modulates the alternative splicing of pyruvate kinase (PKM), leading to metabolic dysregulation and fibroblast activation. In vivo studies showed that fibroblast-specific knockout of Srsf7 in conditional knockout mice conferred resistance to bleomycin-induced pulmonary fibrosis. Importantly, through drug screening, we identified lomitapide as a novel modulator of SRSF7, which effectively mitigated experimental pulmonary fibrosis. Collectively, our findings elucidate a molecular pathway by which SRSF7 drives fibroblast metabolic dysregulation and propose a potential therapeutic strategy for pulmonary fibrosis.

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*

Multi-family therapy (MFT), as an extension of traditional family therapy, refers to a treatment method in which family members from multiple families participate at the same time. Although its application in severe mental disorders such as schizophrenia is mature, its potential in a wider field and its localization pathway need to be systematically discussed. This paper aims to summarize the development, treatment settings and requirements of the early classic model of MFT, analyze its core mechanism, focus on summarizing the emerging application model variants and effectiveness of MFT in medical care (schizophrenia, eating disorders), school education (refusing to intervene in school) and social work (treating ADHD children, traumatized families, etc.), and comprehensively explore the research methods of effect evaluation.However, there are still some limitations in the current researches, such as lax evaluation, unclear specific action pathway, family vulnerability and lack of cross-cultural adaptability research. Finally, the future development direction is prospected to provide reference for promoting the application practice of MFT.

The objective of this study was to investigate whether Stenotrophomonas maltophilia(S.maltophilia)induces ferroptosis,a form of iron-dependent cell death,leading to an inflamma-tory response in RAW 264.7 macrophages by elevating oxidative stress levels.RAW 264.7 cells were stimulated with varying concentrations of S.maltophilia.The concentrations of TNF-αand IL-1β were quantified using ELISA kits to assess the impact of S.maltophilia on the inflammatory response in RAW 264.7 cells.The activities of glutathione(GSH)and malondialdehyde(MDA)levels were measured using GSH and MDA assay kits to evaluate changes in oxidative stress.West-ern blot analysis was employed to detect the expression levels of COX-2,xCT,GPX4,and other proteins involved in ferroptosis signaling pathways,thereby investigating the effect of S.malto-philia on ferroptosis in RAW 264.7 cells.The results demonstrated that S.maltophilia induced concentration-dependent increases in inflammation and oxidative stress in RAW 264.7 cells,up-regulated the expression of COX-2 protein and down-regulated the expression of xCT and GPX4.Pretreatment with the ROS inhibitor N-acetylcysteine(NAC)significantly mitigated the S.malto-philia-induced oxidative stress and ferroptosis signaling activation,thereby alleviating the inflam-matory response.Furthermore,treatment with the ferroptosis inhibitor Fer-1 directly suppressed the activation of the ferroptosis signaling pathway and reversed the inflammation induced by S.maltophilia.These findings suggest that S.maltophilia triggers inflammation in RAW 264.7 cells by activating the ferroptosis signaling pathway via an increase in oxidative stress levels.

OBJECTIVE To retrospectively analyze the drug resistance characteristics of the patients with multidrug-resistant organisms(MDROs)infections who were hospitalized from 2022 to 2023 and observe the effect of multi-disciplinary teamwork(MDT)mode so as to provide scientific bases for prevention and control of MDROs infec-tions and hospital-associated infections.METHODS A total of 639 patients with MDROs infection who were hospi-talized in Jianyang People's Hospital from Jan.2022 to Dec.2023 were recruited as the research subjects.The clinical data were collected from the patients,the drug resistance characteristics of bacteria were analyzed.The effects of MDT and pharmacological supervision on treatment of the patients with MDROs infection were observed and compared.RESULTS The methicillin-resistant Staphylococcus aureus(MRSA)(359 strains,56.18％)was dominant among the pathogens isolated from the 639 patients with MDROs infections,followed by the carbapen-em-resistant Klebsiella pneumoniae(CRKP)(96 strains,15.02％)and carbapenem-resistant Acinetobacter bau-mannii(82 strains,12.83％).Of the patients with MDROs infection,150(23.47％)were from critical care medicine department,94(14.71％)from pediatrics department,and 82(12.83％)from general surgery de-partment.The result of drug susceptibility test showed that the S.aureus strains were susceptible to linezolid,daptomycin,vancomycin and tigecycline;most of the gram-negative bacteria were susceptible to carbapenems,while the A.baumannii strains were highly resistant to the commonly used antibiotics.The total isolation rate of MDROs and the case-time infection rate of MDROs infections were 14.32％and 0.05％,respectively,after MDT and pharmacological supervision were carried out,lower than those before carried out;the effective treatment rate of the patients with MDROs was 76.47％after MDT and pharmacological supervision were carried out,higher than that before they were carried out,and there were significant differences(all P＜0.05).CONCLUSION MDT and pharmacological supervision may improve the curative effect of the patients with MDROs infection and reduce the isolation rate of MDROs as well as the incidence of hospital-associated infections.

To evaluate the efficacy and safety of dye-free submucosal injection solution for gastric endoscopic submucosal dissection (ESD), a retrospective cohort study was performed on data of inpatients with early gastric cancer and precancerous lesions who underwent ESD at the Digestive Endoscopy Center of Jiangsu Province Hospital of Traditional Chinese Medicine from January to December 2020. Cases were divided into dye-free submucosal injection solution group (the observation group) and dye-containing solution group (the control group). A total of 108 cases met the eligibility criteria for analysis (39 VS 69). Baseline characteristics were comparable between the two groups ( P>0.05). Compared with the control group, the observation group showed similar median procedure time (30.5 min VS 35.0 min), median dissection speed (0.3 cm2/min VS 0.4 cm2/min), mean volume of injection solution used (39.2 mL VS 38.8 mL), en bloc resection rate [100.0% (39/39) VS 98.6% (68/69)], and curative resection rate [97.4% (38/39) VS 97.1% (67/69)] (all P>0.05). Postoperative stay was 3.0±0.8 days in the observation group and 3.2±0.8 days in the control group ( t=-0.908, P=0.378). Delayed bleeding occurred in 3 (7.7%) patients VS 2 (2.9%) patients ( P=0.349), and postoperative infection occurred in 3 (7.7%) patients VS 8 (11.6%) patients ( P=0.743), respectively. In gastric ESD, dye-free submucosal injection solution demonstrates efficacy comparable with dye-containing solution and does not appreciably increase the incidence of intraoperative or postoperative complications.

A 71-year-old man with undifferentiated sarcoma was treated with palliative first-line regimen(epirubicin,anlotinib and penpulimab)for 6 cycles and maintained with anlotinib and penpulimab for 30 cycles.He was admitted to the hospital due to chest pain 25 months after the first treatment.The laboratory examination showed cardiac troponin T 1.26 ng·mL-1,N terminal pro B type natriuretic peptide 8,545 pg·mL-1,coronary computed tomography angiography(CTA)showed non-calcified plaque in the left proximal anterior descending branch,severe lumen stenosis,nearly complete occlusion.Emergency CTA was performed on the same day,showing 50％stenosis of the distal left main coronary artery(LMCA);95％stenosis of the left anterior descending(LAD)branch ostium,the LAD branch was medium-sized and showed no stenosis;50％stenosis of the left circumflex branch(LCx),and a cardiac stent was implanted into the LAD branch.The patient has recovered after coronary artery stent implantation.Naranjo's Assessment Scale was used to evaluate the association of suspected drugs,the acute myocardial infarction of this patient was likely associated with the combination of penpulimab and anlotinib.Myocardial infarction is a rare but severe adverse drug reaction of anti-tumor treatment.This article summarizes the related risks and treatment measures to provide a reference for clinical medication safety.