Objective To develop a risk assessment scale for immune checkpoint inhibitor (ICI)-associated myocarditis based on multidisciplinary collaboration, and to evaluate its diagnostic performance. Methods Based on multidisciplinary cooperation, integrating clinical experience from oncology and cardiology, literature data, and patient conditions, a risk assessment scale for ICI-associated myocarditis was developed. A total of 101 patients with malignancies who received immunotherapy at Zhongshan Hospital, Fudan University, from October 2020 to October 2024 were included as the validation cohort. Patients were stratified into low-risk (0-1 point), medium-risk (2-4 points), and high-risk (≥5 points) groups based on their scale scores. The association between pretictive risk stratifications and actual assessment results was assessed using the Cox proportional hazards regression model. The predictive value of the scale for ICI-associated myocarditis was evaluated using receiver operating characteristic (ROC) curve. Agreement between the scale scores and actual assessment results was assessed using Cohen’s Kappa coefficient. Results Based on the scale pretictive results, 28(27.7%), 8(7.9%), 65(64.4%) patients were at low risk, medium risk, and high risk for ICI-related myocarditis, respectively; however, 46(45.5%), 8(7.9%), 47(46.5%) were at low risk, medium risk, and high risk actually. Kaplan-Meier survival analysis showed that the cumulative incidence of ICI-related myocarditis in the high-risk group was significantly higher than that in the medium- and low-risk groups (P＜0.05). In the multivariable-adjusted Cox proportional hazards model, the ICI-related myocarditis risk in high-risk group was about 4 times that in the low-risk group. ROC curve analysis demonstrated that the average area under the curve (AUC) for predicting ICI-related myocarditis was 0.81, with an accuracy of 0.74. The Cohen’s Kappa coefficient was 0.55, indicating moderate agreement. In the actual high-risk group, no patient was predicted to be at low risk; in the actual low-risk group, 16 patients were predicted to be at high risk. Conclusions This risk assessment scale for ICI-associated myocarditis shows high predictive performance. It provides oncologists with a simple yet effective multidisciplinary diagnostic reference tool, potentially enhancing early identification of ICI-associated myocarditis.

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*

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.

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.

Clinical data of a patient with alveolar soft part sarcoma (ASPS) treated at Zhongshan Hospital, Fudan University were retrospectively analyzed. The patient was initially diagnosed with abdominal ASPS with multiple lung metastases. After 6 weeks of treatment with nivolumab and ipilimumab, the patient achieved stable disease (SD). In the 7th week, the treatment was changed to a combination of nivolumab (30 mg, d1, q3w), anlotinib (8 mg, d1-14, q3w) and ipilimumab (50 mg, d1, q6w). The patient remained SD at the 12th week. The patient then underwent iliac artery embolization and intensity-modulated radiation therapy for the lesion in the psoas major muscle, while continuing the combination treatment. By the 24th week, the evaluation showed partial remission (PR) of both primary tumor and lung metastases. The patient experienced mild adverse reactions during treatment.

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.

Objective:To investigate the level of occupational health literacy (OHL) of key populations in Gansu Province in 2022, analyze the influencing factors, and provide a scientific basis for the formulation of health education measures for occupational populations.Methods:From April to December 2022, a stratified cluster random sampling method was adopted to select 11472 workers engaged in frontline jobs in 8 key industries across 86 counties and districts in Gansu Province as the research subjects. The "National Occupational Health Literacy Monitoring and Survey Personal Questionnaire" was used to investigate their OHL. The content includes basic demographic information and occupational health literacy level, and the chi-square test analysis was carried out by SPSS 23.0 software, and the influencing factors were analyzed by logistic regression analysis model.Results:In 2022, a total of 11 118 valid questionnaires were completed in Gansu Province, and the OHL level of key populations in Gansu Province was 48.3%. The OHL levels of occupational health legal knowledge, basic knowledge of occupational health protection, basic skills of occupational health protection and healthy working methods were 50.3%, 81.7%, 33.1% and 63.3%, respectively. In the eight key industries, the OHL level of workers from high to low is: ferrous and non-ferrous metal smelting and rolling processing industry (56.6%) , non-metallic mineral products industry (56.5%) , ferrous and non-ferrous metal mining and dressing industry (54.3%) , environmental sanitation industry (50.3%) , medical and health industry (49.9%) , education industry (40.9%) , transportation industry (40.4%) , and express delivery/takeaway delivery industry (23.3%) . The results of logistics regression analysis showed that gender, age, ethnicity, marital status, education level, average monthly income, nature and scale of employers, and length of service were the influencing factors of OHL level of front-line workers in eight industries in Gansu Province (all P<0.05) . Conclusion:In 2022, the OHL level of key populations in Gansu Province was 48.3%, which needs to be further improved. Occupational health publicity should be strengthened for low-income, low-educated, newly recruited, young and micro-enterprise occupational groups.