Ferroptosis has received great attention as an iron-dependent programmed cell death for efficient cancer therapy. However, with the accumulation of iron in tumor cells, the antioxidant system is activated by reducing glutathione (GSH) with glutathione peroxidase 4 (GPX4), which critically limits the ferroptosis therapeutic effect. Herein, an iron and GPX4 silencing siRNA (siGPX4) co-encapsulated ferritin nanocage (HFn@Fe/siGPX4) was developed to enhance ferroptosis by disruption of redox homeostasis and inhibition of antioxidant enzyme synergistically. The siGPX4 were loaded into the nanocages by pre-incubated with iron, which could significantly improve the loading efficiency of the gene drugs when compared with the reported gene drug loading strategy by ferritin nanocages. And more iron was overloaded into the ferritin through the diffusion method. When HFn@Fe/siGPX4 was taken up by human breast cancer cell MCF-7 in a TfR1-mediated pathway, the excess iron ions in the drug delivery system could for one thing induce ferroptosis by the production of reactive oxygen species (ROS), for another promote siGPX4 escaping from the lysosome to exert gene silencing effect more effectively. Both the in vitro and in vivo results demonstrated that HFn@Fe/siGPX4 could significantly inhibit tumor growth by synergistical ferroptosis. Thus, the developed HFn@Fe/siGPX4 afforded a combined ferroptosis strategy for ferroptosis-based antitumor as well as a novel and efficient gene drug delivery system.

Objective:To investigate the incidence of shoulder work-related musculoskeletal disorders (WMSDs) among occupational population in China, and to explore their intrinsic association with personal and work-related factors.Methods:In April 2024, 73497 valid questionnaires of the Chinese version of the Musculoskeletal Disorders Electronic Questionnaire were retrospectively analyzed from June 2018 to December 2023 in 22 provinces and 29 key industries in China, and the general information, occurrence of WMSDs and related risk factors of key occupational populations in different regions in China were collected. By using Chi-square test and confirmatory factor analysis, the relationship between shoulder fatigue and pain in key occupational groups and individual factors, work type, work posture and work organization was discussed, and the internal relationship was analyzed based on structural equation model.Results:Higher incidence of shoulder fatigue and pain were associated with female, lack of physical exercise, uncomfortable working posture and neck leaning forward ( P<0.05). Structural equation model analysis showed that work type, work posture and work organization were strongly correlated ( r=0.58, 0.55). Work organization and work type were strongly correlated with shoulder fatigue ( r=0.65) and moderately correlated with shoulder fatigue ( r=0.21). Shoulder fatigue was moderately associated with shoulder pain ( r=0.40). Individual factors, work type, work posture and shoulder fatigue could directly affect shoulder pain ( OR=0.07, -0.09, 0.17 and 0.40), and work type and work posture could also indirectly affect shoulder pain through shoulder fatigue ( OR=0.08, 0.03). Work organization only indirectly affected shoulder pain through shoulder fatigue ( OR=0.26) . Conclusion:The main influencing factor of shoulder pain is shoulder fatigue, followed by work posture and individual factors. Structural equation model can better reflect the complex relationship between work type, work posture and work organization and shoulder WMSDs. Improving work posture and work organization may be an effective way to control the influence of shoulder fatigue on shoulder pain.

Objective:To explore the clinical and biochemical characteristics of patients with hyperuricemia according to different pathophysiological subtypes. This may facilitate rapid identification of each subtype in clinical settings and provide evidence for personalized urate-lowering treatment.Methods:Patients diagnosed with hyperuricemia at the Department of Endocrinology and Metabolism, Tenth People′s Hospital of Tongji University between October 2015 and January 2024 were included. Based on 24-h urinary uric acid excretion(UUE) and the fractional excretion of uric acid(FEUA), patients were classified into four subtypes: renal uric acid underexcretion type(RUE), renal uric acid overload type(ROL), combined type and renal normal type. Clinical and biochemical variables-including sex, age, BMI, smoking history, comorbidities, blood glucose, and serum uric acid-were analyzed. Binary logistic regression was used to identify factors associated with each subtype.Results:Among 2 073 patients with hyperuricemia, 55.8% were RUE type, 6.9% were ROL type, 31.3% were combined type and 6.0% were renal normal type. RUE type had lower blood glucose levels and fewer cases of diabetes [ OR=0.685(95% CI 0.478-0.980), P<0.05]. ROL type showed a higher incidence of tophi, positively correlated with smoking history [ OR=1.672(95% CI 1.009-2.771), P<0.05], and negatively correlated with serum uric acid levels [ OR=0.994(95% CI 0.990-0.998), P=0.001]. Combined type had the youngest onset age, shortest disease duration, and the fewest comorbidities, and was associated with higher BMI [ OR=1.035(95% CI 1.001-1.070), P<0.05]. Renal normal type had the oldest age of onset, the highest proportion of female patients and comorbidities, and was associated with lower serum uric acid levels[ OR=0.994(95% CI 0.989-0.998), P=0.007], higher BMI[ OR=1.064(95% CI 1.003-1.129), P<0.05], and increased tophi incidence[ OR=2.261(95% CI 1.206-4.237), P=0.011]. Conclusion:Each pathophysiological subtype of hyperuricemia exhibits distinct clinical and biochemical characteristics, which may serve as useful references for subtype identification and personalized management in clinical practice.

The objective of this study was to evaluate the protective effect and possible related mechanisms of Sophora subprostrate polysaccharide(SSP)on intestinal epithelial cell injury in-duced by Tert-Butyl hydroperoxide(TBHP).The optimal dose of TBHP and the safe concentra-tion range of SSP were determined using the MTT method.In this study,IPEC-J2 cells were divid-ed into five groups:the control group,the model group,the SSPL group,the SSPM group and the SSPH group,and the cell morphology,cell survival rate and LDH release rate were observed and measured.The content of intracellular reactive ROS was observed and determined by DCFH-DA staining.The content of MDA in the supernatant and the antioxidant index of cells were determined by the reagent kit.Transcriptome technology was employed to analyze the potential mechanisms by which SSP mitigates oxidative damage in IPEC-J2 cells.The results showed that treatment with 625 μmol/L TBHP for 2 h significantly reduced the activity of IPEC-J2 cells,markedly increased LDH release(P＜0.05),inhibited CAT superoxide SOD and glutathione GPX activities(P＜0.05),and significantly elevated MDA and ROS levels(P＜0.05).Compared to the model group,after SSP treatment,intracellular ROS levels were significantly reduced(P＜0.05),while CAT,SOD,and GPX activities were significantly increased(P＜0.05),and MDA content and LDH re-lease were significantly decreased(P＜0.05)in a dose-dependent manner.Transcriptome analysis revealed that TBHP treatment significantly altered the transcriptional profiles of IPEC-J2 cells,while SSP treatment could restore the transcriptional profiles of the damaged cells to a certain ex-tent.Gene ontology(GO)and Kyoto encyclopedia of genes and genomes(KEGG)indicated that the differentially expressed genes between the CC and TBHP groups were significantly enriched in oxidative phosphorylation,ribosome,and other pathways.Meanwhile,the differentially expressed genes between the SSP and TBHP groups were mainly enriched in oxidative phosphorylation,ap-optosis,glyoxylate and dicarboxylate metabolism,and other pathways.These results suggest that TBHP may disrupt normal oxidative respiration in IPEC-J2 cells by affecting oxidative phospho-rylation and interfering with metabolism pathways involving glycine,serine,and threonine,leading to oxidative damage in intestinal epithelial cells.Conversely,SSP treatment may potentially restore oxidative phosphorylation processes,alleviate lysosomal damage,reduce cell apoptosis,and miti-gate oxidative damage in intestinal epithelial cells through modulation of oxidative phosphoryla-tion,apoptosis,and lysosomal pathways.This discovery provides a theoretical basis for the clinical application of SSP in alleviating oxidative damage in the porcine intestinal tract.

The objective of this study was to evaluate the protective effect and possible related mechanisms of Sophora subprostrate polysaccharide(SSP)on intestinal epithelial cell injury in-duced by Tert-Butyl hydroperoxide(TBHP).The optimal dose of TBHP and the safe concentra-tion range of SSP were determined using the MTT method.In this study,IPEC-J2 cells were divid-ed into five groups:the control group,the model group,the SSPL group,the SSPM group and the SSPH group,and the cell morphology,cell survival rate and LDH release rate were observed and measured.The content of intracellular reactive ROS was observed and determined by DCFH-DA staining.The content of MDA in the supernatant and the antioxidant index of cells were determined by the reagent kit.Transcriptome technology was employed to analyze the potential mechanisms by which SSP mitigates oxidative damage in IPEC-J2 cells.The results showed that treatment with 625 μmol/L TBHP for 2 h significantly reduced the activity of IPEC-J2 cells,markedly increased LDH release(P＜0.05),inhibited CAT superoxide SOD and glutathione GPX activities(P＜0.05),and significantly elevated MDA and ROS levels(P＜0.05).Compared to the model group,after SSP treatment,intracellular ROS levels were significantly reduced(P＜0.05),while CAT,SOD,and GPX activities were significantly increased(P＜0.05),and MDA content and LDH re-lease were significantly decreased(P＜0.05)in a dose-dependent manner.Transcriptome analysis revealed that TBHP treatment significantly altered the transcriptional profiles of IPEC-J2 cells,while SSP treatment could restore the transcriptional profiles of the damaged cells to a certain ex-tent.Gene ontology(GO)and Kyoto encyclopedia of genes and genomes(KEGG)indicated that the differentially expressed genes between the CC and TBHP groups were significantly enriched in oxidative phosphorylation,ribosome,and other pathways.Meanwhile,the differentially expressed genes between the SSP and TBHP groups were mainly enriched in oxidative phosphorylation,ap-optosis,glyoxylate and dicarboxylate metabolism,and other pathways.These results suggest that TBHP may disrupt normal oxidative respiration in IPEC-J2 cells by affecting oxidative phospho-rylation and interfering with metabolism pathways involving glycine,serine,and threonine,leading to oxidative damage in intestinal epithelial cells.Conversely,SSP treatment may potentially restore oxidative phosphorylation processes,alleviate lysosomal damage,reduce cell apoptosis,and miti-gate oxidative damage in intestinal epithelial cells through modulation of oxidative phosphoryla-tion,apoptosis,and lysosomal pathways.This discovery provides a theoretical basis for the clinical application of SSP in alleviating oxidative damage in the porcine intestinal tract.

Objective:To explore the clinical and biochemical characteristics of patients with hyperuricemia according to different pathophysiological subtypes. This may facilitate rapid identification of each subtype in clinical settings and provide evidence for personalized urate-lowering treatment.Methods:Patients diagnosed with hyperuricemia at the Department of Endocrinology and Metabolism, Tenth People′s Hospital of Tongji University between October 2015 and January 2024 were included. Based on 24-h urinary uric acid excretion(UUE) and the fractional excretion of uric acid(FEUA), patients were classified into four subtypes: renal uric acid underexcretion type(RUE), renal uric acid overload type(ROL), combined type and renal normal type. Clinical and biochemical variables-including sex, age, BMI, smoking history, comorbidities, blood glucose, and serum uric acid-were analyzed. Binary logistic regression was used to identify factors associated with each subtype.Results:Among 2 073 patients with hyperuricemia, 55.8% were RUE type, 6.9% were ROL type, 31.3% were combined type and 6.0% were renal normal type. RUE type had lower blood glucose levels and fewer cases of diabetes [ OR=0.685(95% CI 0.478-0.980), P<0.05]. ROL type showed a higher incidence of tophi, positively correlated with smoking history [ OR=1.672(95% CI 1.009-2.771), P<0.05], and negatively correlated with serum uric acid levels [ OR=0.994(95% CI 0.990-0.998), P=0.001]. Combined type had the youngest onset age, shortest disease duration, and the fewest comorbidities, and was associated with higher BMI [ OR=1.035(95% CI 1.001-1.070), P<0.05]. Renal normal type had the oldest age of onset, the highest proportion of female patients and comorbidities, and was associated with lower serum uric acid levels[ OR=0.994(95% CI 0.989-0.998), P=0.007], higher BMI[ OR=1.064(95% CI 1.003-1.129), P<0.05], and increased tophi incidence[ OR=2.261(95% CI 1.206-4.237), P=0.011]. Conclusion:Each pathophysiological subtype of hyperuricemia exhibits distinct clinical and biochemical characteristics, which may serve as useful references for subtype identification and personalized management in clinical practice.

Objective:To investigate the incidence of shoulder work-related musculoskeletal disorders (WMSDs) among occupational population in China, and to explore their intrinsic association with personal and work-related factors.Methods:In April 2024, 73497 valid questionnaires of the Chinese version of the Musculoskeletal Disorders Electronic Questionnaire were retrospectively analyzed from June 2018 to December 2023 in 22 provinces and 29 key industries in China, and the general information, occurrence of WMSDs and related risk factors of key occupational populations in different regions in China were collected. By using Chi-square test and confirmatory factor analysis, the relationship between shoulder fatigue and pain in key occupational groups and individual factors, work type, work posture and work organization was discussed, and the internal relationship was analyzed based on structural equation model.Results:Higher incidence of shoulder fatigue and pain were associated with female, lack of physical exercise, uncomfortable working posture and neck leaning forward ( P<0.05). Structural equation model analysis showed that work type, work posture and work organization were strongly correlated ( r=0.58, 0.55). Work organization and work type were strongly correlated with shoulder fatigue ( r=0.65) and moderately correlated with shoulder fatigue ( r=0.21). Shoulder fatigue was moderately associated with shoulder pain ( r=0.40). Individual factors, work type, work posture and shoulder fatigue could directly affect shoulder pain ( OR=0.07, -0.09, 0.17 and 0.40), and work type and work posture could also indirectly affect shoulder pain through shoulder fatigue ( OR=0.08, 0.03). Work organization only indirectly affected shoulder pain through shoulder fatigue ( OR=0.26) . Conclusion:The main influencing factor of shoulder pain is shoulder fatigue, followed by work posture and individual factors. Structural equation model can better reflect the complex relationship between work type, work posture and work organization and shoulder WMSDs. Improving work posture and work organization may be an effective way to control the influence of shoulder fatigue on shoulder pain.

Abstract: Objective　To analyze the surveillance of Mycobacterium tuberculosis/HIV (TB/HIV) co-infection in Liaoning Province from 2016 to 2021, providing a scientific basis for formulating future prevention and control measures applicable to the province-wide co-infection. Methods　A descriptive analysis was conducted on patient registration, two-way screening, and treatment information from the annual report of patients with TB/HIV co-infection in Liaoning Province from 2016 to 2021. Results From 2016 to 2021, 222 cases of TB/HIV co-infection were registered in Liaoning Province, accounting for 0.16% (222/136 709) of TB patients and 1.42% (222/15 584) of HIV/AIDS patients. In HIV/AIDS, the symptom screening rate was 96.01%, showing a downward trend (χ2trend=982.28, P<0.05). The TB detection rate was 0.47%, also showing a downward trend (χ2trend=36.56, P<0.05), while the chest radiograph or sputum detection rate was 94.61%, showing an overall upward trend (χ2trend=96.5, P<0.05). Among TB patients, 65 188 were tested for HIV antibodies, with a detection rate of 47.68%, which showed an overall upward trend (χ2trend=3 326.38, P<0.05). There were 39 HIV-positive cases detected, with the positive detection rate in TB patients decreasing from 0.12% to 0.07%. From 2016 to 2021, the majority of co-infected patients were male and ≥15 years old, with 496 cases (92.36%) of males and 41 cases (7.64%) of females. Among the 537 patients with co-infection, 47 cases (8.75%) received anti-tuberculosis therapy alone, 72 cases (13.41%) received anti-HIV therapy alone, and 408 cases (75.98%) received combined therapy, with an overall downward trend (χ2trend=9.54, P<0.05). Conclusions Focus should be placed on the male population and those aged ≥15 years, with future efforts aimed at enhancing two-way screening work among TB and HIV/AIDS patients and improving the rate of combined treatment.