ObjectiveTo investigate the mechanism of Xiezhuo Jiedu prescription in the treatment of ulcerative colitis （UC） by inhibiting ferroptosis and alleviating intestinal mucosal injury based on the nuclear factor E₂ related factor 2/solute carrier family 7 member/glutathione peroxidase 4 （Nrf2/SLC7A11/GPX4） signaling pathway. MethodsA total of 60 male SD rats were divided into a normal group， a model group， high- and low-dose Xiezhuo Jiedu prescription groups （26.64 and 13.32 g·kg^-1， respectively）， a ferroptosis inhibitor group （Ferrostatin-1， 0.005 g·kg^-1）， and a mesalazine group （0.27 g·kg^-1）， with 10 rats in each group. A UC rat model was established by intrarectal administration of trinitrobenzene sulfonic acid （TNBS）-ethanol. The normal group and the model group were intragastrically administered normal saline. The other groups were given intragastric administration according to the corresponding dosage for 7 d. The general condition， disease activity index （DAI） score， colon length， and mucosal injury index （CDMI） score were observed in each group. The pathological changes of colon tissue in each group were observed by hematoxylin-eosin （HE） staining. The intestinal mucosa and mitochondrial morphology in each group were observed by transmission electron microscopy. The expression levels of Occludin， Claudin-1， mucin 2 （MUC2）， and E-cadherin in intestinal tissue were detected by immunofluorescence （IF）. Enzyme-linked immunosorbent assay （ELISA） was used to detect the expression levels of serum tumor necrosis factor-α （TNF-α）， interleukin-6 （IL-6）， and interleukin-10 （IL-10） in each group， and a lactic acid assay kit or ELISA was employed to detect the expression levels of reactive oxygen species （ROS）， ferrous ions （Fe²⁺）， glutathione （GSH）， malondialdehyde （MDA）， 4-hydroxynonenal （4-HNE）， diamine oxidase （DAO）， and D-lactate （D-LA）. Real-time quantitative polymerase chain reaction （Real-time PCR） was applied to detect the mRNA expression levels of Nrf2， SLC7A11， GPX4， Occludin， Claudin-1， MUC2， and E-cadherin in each group， and Western blot was adopted to detect the protein expression levels of Nrf2， p-Nrf2， SLC7A11， and GPX4 in each group. ResultsCompared with the normal group， rats in the model group exhibited listlessness， sluggish response， and mucopurulent and bloody stools. The model group also showed significantly increased DAI score， colon length， CDMI score， and expression levels of TNF-α， IL-6， ROS， Fe²⁺， MDA， 4-HNE， DAO， and D-LA （P<0.01）. In addition， it presented significantly decreased IF values of Occludin， Claudin-1， MUC2， and E-cadherin and mRNA and protein expression levels of IL-10， GSH， Nrf2， p-Nrf2， SLC7A11， and GPX4 （P<0.01）. There were different degrees of improvement in each administration group after treatment， and the improvement was the most significant in the high-dose Xiezhuo Jiedu prescription group （P<0.01）. ConclusionXiezhuo Jiedu prescription may alleviate intestinal mucosal injury by inhibiting ferroptosis of intestinal epithelial cells via regulating the Nrf2/SLC7A11/GPX4 signaling pathway， thereby exhibiting efficacy in the treatment of UC.

Objective:To explore the structural equation model to explore the levels of work-related musculoskeletal disorders (WMSDs) and various risk factors in the feet and ankle of China's occupational population, providing scientific basis for for preventing WMSDs in feet and ankles.Methods:Data of 73497 national occupational epidemiological cases were selected from June 2018 to December 2023 used the Chinese version of the Electronic Questionnaire on Musculoskeletal Disorders. The adverse ergonomic factors and their source classification standard and confirmatory factor analysis were used to investigate foot and ankle WMSDs and their related risk factors (including individual factors, work organization, work posture, work type, fatigue, etc.) in key occupational groups in China, and structural equation model hypothesis, fitting, verification, and path and intermediary effect analysis were carried out. The model fit evaluation indexes included Chi-square specific degrees of freedom ( χ2/ df), gauge fit index (NFI), Tucker Lewis index (TLI), goodness of Fit index (GFI), adjusted Goodness of Fit index (AGFI) and approximate root mean square error (RMSEA) . Results:A total of 73497 occupational workers were surveyed, with local muscle fatigue and WMSDs incidence rates in the feet and ankles being 17.17% and 12.06%, respectively. The fitting index of the adjusted structural equation model basically meets the standard (GFI=1, AGFI=1, RMESA=0.042, NFI=0.716, TLI=0.663). The top three factors affecting feet and ankle WMSDs are feet and ankle muscle fatigue, work type, and work organization, with standardized path coefficients of 0.221, 0.105, and 0.095, respectively. The top two factors affecting feet and ankle muscle fatigue are work organization and work type, with standardized path coefficients of 0.548 and 0.383, respectively. Feet and ankle muscle fatigue, work type, work organization, and work posture have a direct effect on feet and ankle WMSDs, with effect values of 0.221, 0.105, 0.095, and 0.077, respectively. The organization and type of work can also have indirect effects through feet and ankle muscle fatigue, with effect values of 0.121 and 0.084, respectively.Conclusion:Feet and ankle muscle fatigue has a direct impact on WMSDs, and plays a mediating role between ankle and ankle WMSDs caused by work organization and work type. Feet and ankle muscle fatigue is an important pathway leading to feet and ankle WMSDs. It is recommended that employers and managers detect job fatigue early and take corresponding prevention and intervention measures, which can play a key role in preventing feet and ankle WMSDs.

Objective:To explore the structural relationship between WMSDs in the upper limbs and various risk factors in the occupational population in China, based on a large sample epidemiological survey and structural equation analysis, and to establish a structural equation model, so as to lay a foundation for the prevention and control of such diseases.Methods:The Chinese version of the Musculoskeletal Disorders Electronic Questionnaire was used to conduct a nationwide survey on the prevalence of WMSDs in the upper extremity. Six factors related to WMSDs in the upper extremity were extracted by the classification standard of adverse ergonomic factors and their source and confirmatory factor analysis, including work organization, work type, upper extremity work posture, individual factors, upper extremity fatigue and upper extremity WMSDs. The structural equation analysis was carried out and the structural equation model was established.Results:The incidence of WMSDs and fatigue in the upper limbs was 24.44% and 43.76%, respectively. The adjusted structural equation model fitting indicators were generally up to the standard (GFI=1.000, AGFI=1.000, RMSEA=0.043, NFI=0.808, TLI=0.784) . The four exogenous latent variables of work organization, work type, upper limb work posture and individual factors were correlated. There was a strong positive correlation between job type and upper limb work posture ( r=0.865) , a moderate positive correlation between work organization and job type and upper limb work posture ( r=0.570, 0.490) , and a weak negative correlation between individual factors and the other three exogenous latent variables. Upper limb work posture and individual factors had direct effects on upper limb WMSDs, and the effect coefficients were 0.10 and 0.06, respectively. Upper limb fatigue played a mediating role between work organization, work type, upper limb work posture and upper limb WMSDs. The effect coefficient was 0.46, and the composition ratios of indirect effects were 100.0%, 100.0%, and 38.3%, respectively. The direct path effect of upper limb work posture, individual factors and upper limb WMSDs was weaker than the mediating path through upper limb fatigue. Conclusion:When carrying out the prevention and control of upper limbWMSDs, it is necessary to comprehensively consider the pathogenesis path of upper limb muscle fatigue and upper limb WMSDs caused by work organization, work type, and upper limb work posture, so as to provide theoretical reference for improving the prevention and control level of such diseases.

Body weight abnormalities, including overweight, obesity, and underweight, have become a dual public health challenge in Chinese adults: overweight and obesity lead to a variety of chronic complications, while underweight increases the risks of malnutrition, sarcopenia, and organ dysfunction. To systematically address these issues, multidisciplinary experts in endocrinology, sports science, nutrition, and psychiatry from various regions have held multiple weight management seminars. Based on the latest epidemiological data and clinical evidence, they expanded the guideline to include assessment and intervention strategies for underweight, in addition to the core content of obesity management. This guideline outlines the etiological mechanisms, evaluation methods, and multidimensional management strategies for overweight and obesity, covering key areas such as diagnosis and assessment, medical nutrition therapy, exercise prescription, pharmacological intervention, and psychological support. It is intended to provide a scientific and standardized approach to weight management across the adult population, aiming to curb the rising prevalence of obesity, mitigate complications associated with abnormal body weight, and improve nutritional status and overall quality of life.

Objective To investigate the factors associated with unplanned readmission within 30 days after discharge in adult patients who underwent coronary artery bypass grafting (CABG) and to develop and validate a risk prediction model. Methods A retrospective analysis was conducted on the clinical data of patients who underwent isolated CABG at the Nanjing First Hospital between January 2020 and June 2024. Data from January 2020 to August 2023 were used as a training set, and data from September 2023 to June 2024 were used as a validation set. In the training set, patients were divided into a readmission group and a non-readmission group based on whether they had unplanned readmission within 30 days post-discharge. Clinical data between the two groups were compared, and logistic regression was performed to identify independent risk factors for unplanned readmission. A risk prediction model and a nomogram were constructed, and internal validation was performed to assess the model’s performance. The validation set was used for validation. Results A total of 2 460 patients were included, comprising 1 787 males and 673 females, with a median age of 70 (34, 89) years. The training set included 1 932 patients, and the validation set included 528 patients. In the training set, there were statistically significant differences between the readmission group (79 patients) and the non-readmission group (1 853 patients) in terms of gender, age, carotid artery stenosis, history of myocardial infarction, preoperative anemia, and heart failure classification (P<0.05). The main causes of readmission were poor wound healing, postoperative pulmonary infections, and new-onset atrial fibrillation. Multivariable logistic regression analysis revealed that females [OR=1.659, 95%CI (1.022, 2.692), P=0.041], age [OR=1.042, 95%CI (1.011, 1.075), P=0.008], carotid artery stenosis [OR=1.680, 95%CI (1.130, 2.496), P=0.010], duration of first ICU stay [OR=1.359, 95%CI (1.195, 1.545), P<0.001], and the second ICU admission [OR=4.142, 95%CI (1.507, 11.383), P=0.006] were independent risk factors for unplanned readmission. In the internal validation, the area under the curve (AUC) was 0.806, and the net benefit rate of the clinical decision curve analysis (DCA) was >3%. In the validation set, the AUC was 0.732, and the DCA net benefit rate ranged from 3% to 48%. Conclusion Females, age, carotid artery stenosis, duration of first ICU stay, and second ICU admission are independent risk factors for unplanned readmission within 30 days after isolated CABG. The constructed nomogram demonstrates good predictive power.

Objective: To study the effect of metformin sensitizing pancreatic cancer cells with radiotherapy, with a focus on elucidating the underlying mechanisms of radiotherapy resistance. In particular, the role of the PERK/P-eIF2/ATF4 signaling pathway in mediating these effects was preliminarily explored. Methods : Pancreatic cancer cell lines(PANC-1 and PANC-2) were categorized into control, radiotherapy, and drug treatment groups. Following the respective treatments, cell proliferation inhibition was assessed using the CCK-8 assay, colony formation assays, and cell death staining. Senescence was quantified by β-galactosidase(SA-β-Gal) staining. The expression of cell cycle regulators(P21, P16, γ-H2AX), apoptosis markers(Bax, Bcl-2, Cleaved caspase-3), and pathway-related proteins(PERK, P-eIF2, ATF4) was evaluated by Western blot and immunofluorescence. To further investigate the role of the PERK/P-eIF2/ATF4 axis in metformin-mediated modulation of pancreatic cancer cell senescence and radiosensitization, selective inhibitors(GSK2606414) and agonists(MK-28) of PERK were employed. Results : Radiotherapy markedly upregulated senescence-associated markers(P21, P16, γ-H2AX, and β-galactosidase activity) in pancreatic cancer cells. Senescent cells exhibited enhanced proliferative activity and increased tumor volume both in vitro and in vivo. Metformin mitigated radiotherapy-induced senescence by reducing the expression of senescence markers and significantly suppressing the clonogenic and proliferative capacity of treated cells. Mechanistically, radiotherapy activated the PERK signaling pathway, leading to increased expression of PERK, P-eIF2, and ATF4, thereby driving cellular senescence. Pharmacological inhibition of PERK reduced β-galactosidase activity, while PERK activation further promoted the expression of senescence-associated proteins—an effect that was reversed by metformin. Conclusion Metformin inhibits the activation of the PERK/P-eIF2/ATF4 signaling pathway in pancreatic cancer cells following radiotherapy, thereby delaying cellular senescence and reducing the associated radiotherapy resistance of senescent cells. This modulation contributes to the sensitization of pancreatic cancer cells to radiotherapy.

G protein-coupled receptors(GPCRs)are the largest family of membrane proteins in eukaryotes,with nearly 800 genes coding for these proteins.They are involved in many physiological processes,such as light perception,taste and smell,neurotransmitter,metabolism,endocrine and exocrine,cell growth and migration.Importantly,GPCRs and their ligands are the targets of approximately one third of all mar-keted drugs.GPCRs are traditionally known for their role in transmitting signals from the extracellular environment to the cell's interior via the plasma membrane.However,emerging evidence suggests that GPCRs are also localized on mitochondria,where they play critical roles in modulating mitochondrial functions.These mitochondrial GPCRs(mGPCRs)can influence processes such as mitochondrial respi-ration,apoptosis,and reactive oxygen species(ROS)production.By interacting with mitochondrial signaling pathways,mGPCRs contribute to the regulation of energy metabolism and cell survival.Their presence on mitochondria adds a new layer of complexity to the understanding of cellular signaling,highlighting the organelle's role as not just an energy powerhouse but also a crucial hub for signal transduction.This expanding understanding of mGPCR function on mitochondria opens new avenues for research,particularly in the context of diseases where mitochondrial dysfunction plays a key role.Ab-normalities in the phase conductance pathway of GPCRs located on mitochondria are closely associated with the development of systemic diseases such as cardiovascular disease,diabetes,obesity and Alz-heimer's disease.In this review,we examined the various types of GPCRs identified on mitochondrial membranes and analyzed the complex relationships between mGPCRs and the pathogenesis of various diseases.We aim to provide a clearer understanding of the emerging significance of mGPCRs in health and disease,and to underscore their potential as therapeutic targets in the treatment of these conditions.

G protein-coupled receptors (GPCRs) are the largest family of membrane proteins in eukaryotes, with nearly 800 genes coding for these proteins. They are involved in many physiological processes, such as light perception, taste and smell, neurotransmitter, metabolism, endocrine and exocrine, cell growth and migration. Importantly, GPCRs and their ligands are the targets of approximately one third of all marketed drugs. GPCRs are traditionally known for their role in transmitting signals from the extracellular environment to the cell's interior via the plasma membrane. However, emerging evidence suggests that GPCRs are also localized on mitochondria, where they play critical roles in modulating mitochondrial functions. These mitochondrial GPCRs (mGPCRs) can influence processes such as mitochondrial respiration, apoptosis, and reactive oxygen species (ROS) production. By interacting with mitochondrial signaling pathways, mGPCRs contribute to the regulation of energy metabolism and cell survival. Their presence on mitochondria adds a new layer of complexity to the understanding of cellular signaling, highlighting the organelle's role as not just an energy powerhouse but also a crucial hub for signal transduction. This expanding understanding of mGPCR function on mitochondria opens new avenues for research, particularly in the context of diseases where mitochondrial dysfunction plays a key role. Abnormalities in the phase conductance pathway of GPCRs located on mitochondria are closely associated with the development of systemic diseases such as cardiovascular disease, diabetes, obesity and Alzheimer's disease. In this review, we examined the various types of GPCRs identified on mitochondrial membranes and analyzed the complex relationships between mGPCRs and the pathogenesis of various diseases. We aim to provide a clearer understanding of the emerging significance of mGPCRs in health and disease, and to underscore their potential as therapeutic targets in the treatment of these conditions.

Forensic medicine has been designated as a first-level discipline,presenting new opportunities and challenges for the development of forensic medicine.Since the 1980s,the establishment of foren-sic medicine discipline and the cultivation of high-level forensic talents have become hot topics in the development of forensic medicine in China.Since the 13th Five-Year Plan,the forensic team of Shanxi Medical University has been aiming at the forefront,proposing the development goals of"Five First-class"and the discipline development path"Six Major Achievements".It has selected benchmark disci-plines,identified gaps in disciplinary development,unified thoughts,formulated completion timelines,concentrated superior resources,assigned tasks to individuals,and created an"Organized Fill-in-the-Blank Format"forensic medicine discipline construction model with the characteristics of the new era.The construction model of forensic medicine has achieved good results in the goals,discipline frame-work,scientific research,talent cultivation,discipline team and platform construction,forming a rela-tively complete discipline construction and management system,and accumulating valuable experience for the construction of first-level discipline and high-level talent cultivation of forensic medicine.

The patient, assigned female at birth and aged 1 year and 7 months, presented with clinical manifestations of 46,XY disorders of sex development. The external genitalia exhibited a severely undermasculinized phenotype. Laboratory tests and gonadal biopsy indicated poor Leydig cell function and good Sertoli cell function. Genetic testing revealed compound heterozygous mutations of c.867-2A>C and c.547G>A (p.G183R) in the LHCGR gene. The patient was ultimately diagnosed with type II Leydig cell hypoplasia. Type II Leydig cell hypoplasia presents a broad spectrum of clinical phenotypes, characterized by a lack of parallel function between Leydig cells and Sertoli cells, and significant individual variability in spermatogenesis and gender assignment. This condition should be considered when there is poor Leydig cell function but good development of Wolffian duct derivatives.
Female ; Humans ; Infant ; Disorder of Sex Development, 46,XY/genetics* ; Leydig Cells/pathology* ; Mutation ; Receptors, LH/genetics* ; Testis/abnormalities*