Objective To construct a prediction model for the population with hypertension and diabetes to assess the risk of chronic kidney disease (CKD), and to provide a scientific basis for formulating targeted CKD prevention and control measures. Methods Based on physical examination data from community residents aged 60 years and above in Nanjing in 2022, 10 221 patients with hypertension and diabetes were selected as the study subjects. Variables associated with CKD prevalence were screened using univariate analysis, and further variable selection was performed using LASSO regression. Finally, a CKD risk prediction model was constructed based on logistic regression. The model's performance was evaluated using the ROC curve and calibration curve. Results The prevalence rate of CKD in the study population was 22.71%, with a mean age of 71.66 years. LASSO regression identified seven variables associated with CKD: age, blood urea nitrogen (BUN), hemoglobin, uric acid, triglyceride-glucose (TyG) index, urine protein-to-creatinine ratio (UPCR), and medical insurance type. The final logistic regression model incorporated six variables: age [OR=1.067 (95% CI: 1.058-1.076)], BUN [OR=1.377 (95% CI: 1.338-1.418)], hemoglobin [OR=0.992 (95% CI: 0.989-0.995)], uric acid [OR=1.004 (95% CI: 1.003-1.004)], TyG index [OR=1.445 (95% CI: 1.324-1.577)], and self-payment medical insurance [OR=1.732 (95% CI: 1.542-1.945)]. The model had an AUC of 0.759 (95% CI: 0.747-0.770) and a Brier score of 0.140 (95% CI: 0.136-0.145), indicating good predictive performance. The calibration curve showed good agreement between the predicted risk and the observed value. Conclusion The constructed LASSO-logistic regression risk prediction model in this study can effectively assess the risk of CKD in elderly individuals aged 60 years and above with hypertension and diabetes, providing a basis for early identification of high-risk individuals and the formulation of targeted CKD prevention and control measures.

Purpose: The genomic characteristics of uterine sarcomas have not been fully elucidated. This study aimed to explore the genomic landscape of the uterine sarcomas (USs). Materials and Methods: Comprehensive genomic analysis through RNA-sequencing was conducted. Gene fusion, differentially expressed genes (DEGs), signaling pathway enrichment, immune cell infiltration, and prognosis were analyzed. A deep learning model was constructed to predict the survival of US patients. Results: A total of 71 US samples were examined, including 47 endometrial stromal sarcomas (ESS), 18 uterine leiomyosarcomas (uLMS), three adenosarcomas, two carcinosarcomas, and one uterine tumor resembling an ovarian sex-cord tumor. ESS (including high-grade ESS [HGESS] and low-grade ESS [LGESS]) and uLMS showed distinct gene fusion signatures; a novel gene fusion site, MRPS18A–PDC-AS1 could be a potential diagnostic marker for the pathology differential diagnosis of uLMS and ESS; 797 and 477 uterine sarcoma DEGs (uDEGs) were identified in the ESS vs. uLMS and HGESS vs. LGESS groups, respectively. The uDEGs were enriched in multiple pathways. Fifteen genes including LAMB4 were confirmed with prognostic value in USs; immune infiltration analysis revealed the prognositic value of myeloid dendritic cells, plasmacytoid dendritic cells, natural killer cells, macrophage M1, monocytes and hematopoietic stem cells in USs; the deep learning model named Max-Mean Non-Local multi-instance learning (MMN-MIL) showed satisfactory performance in predicting the survival of US patients, with the area under the receiver operating curve curve reached 0.909 and accuracy achieved 0.804. Conclusion USs harbored distinct gene fusion characteristics and gene expression features between HGESS, LGESS, and uLMS. The MMN-MIL model could effectively predict the survival of US patients.

Purpose: The genomic characteristics of uterine sarcomas have not been fully elucidated. This study aimed to explore the genomic landscape of the uterine sarcomas (USs). Materials and Methods: Comprehensive genomic analysis through RNA-sequencing was conducted. Gene fusion, differentially expressed genes (DEGs), signaling pathway enrichment, immune cell infiltration, and prognosis were analyzed. A deep learning model was constructed to predict the survival of US patients. Results: A total of 71 US samples were examined, including 47 endometrial stromal sarcomas (ESS), 18 uterine leiomyosarcomas (uLMS), three adenosarcomas, two carcinosarcomas, and one uterine tumor resembling an ovarian sex-cord tumor. ESS (including high-grade ESS [HGESS] and low-grade ESS [LGESS]) and uLMS showed distinct gene fusion signatures; a novel gene fusion site, MRPS18A–PDC-AS1 could be a potential diagnostic marker for the pathology differential diagnosis of uLMS and ESS; 797 and 477 uterine sarcoma DEGs (uDEGs) were identified in the ESS vs. uLMS and HGESS vs. LGESS groups, respectively. The uDEGs were enriched in multiple pathways. Fifteen genes including LAMB4 were confirmed with prognostic value in USs; immune infiltration analysis revealed the prognositic value of myeloid dendritic cells, plasmacytoid dendritic cells, natural killer cells, macrophage M1, monocytes and hematopoietic stem cells in USs; the deep learning model named Max-Mean Non-Local multi-instance learning (MMN-MIL) showed satisfactory performance in predicting the survival of US patients, with the area under the receiver operating curve curve reached 0.909 and accuracy achieved 0.804. Conclusion USs harbored distinct gene fusion characteristics and gene expression features between HGESS, LGESS, and uLMS. The MMN-MIL model could effectively predict the survival of US patients.

Purpose: The genomic characteristics of uterine sarcomas have not been fully elucidated. This study aimed to explore the genomic landscape of the uterine sarcomas (USs). Materials and Methods: Comprehensive genomic analysis through RNA-sequencing was conducted. Gene fusion, differentially expressed genes (DEGs), signaling pathway enrichment, immune cell infiltration, and prognosis were analyzed. A deep learning model was constructed to predict the survival of US patients. Results: A total of 71 US samples were examined, including 47 endometrial stromal sarcomas (ESS), 18 uterine leiomyosarcomas (uLMS), three adenosarcomas, two carcinosarcomas, and one uterine tumor resembling an ovarian sex-cord tumor. ESS (including high-grade ESS [HGESS] and low-grade ESS [LGESS]) and uLMS showed distinct gene fusion signatures; a novel gene fusion site, MRPS18A–PDC-AS1 could be a potential diagnostic marker for the pathology differential diagnosis of uLMS and ESS; 797 and 477 uterine sarcoma DEGs (uDEGs) were identified in the ESS vs. uLMS and HGESS vs. LGESS groups, respectively. The uDEGs were enriched in multiple pathways. Fifteen genes including LAMB4 were confirmed with prognostic value in USs; immune infiltration analysis revealed the prognositic value of myeloid dendritic cells, plasmacytoid dendritic cells, natural killer cells, macrophage M1, monocytes and hematopoietic stem cells in USs; the deep learning model named Max-Mean Non-Local multi-instance learning (MMN-MIL) showed satisfactory performance in predicting the survival of US patients, with the area under the receiver operating curve curve reached 0.909 and accuracy achieved 0.804. Conclusion USs harbored distinct gene fusion characteristics and gene expression features between HGESS, LGESS, and uLMS. The MMN-MIL model could effectively predict the survival of US patients.

Objective: To investigate the influencing factors of overactive bladder (OAB) in college freshmen and the impacts of OAB on their mental health, quality of life and social interaction. Methods: An epidemiological questionnaire survey was conducted in an anonymous manner on the prevalence of OAB among 5300 freshmen aged 17 to 22 years enrolled in the 2023—2024 academic year in Xinxiang Medical University and Sanquan College of Xinxiang Medical University.The questionnaire included questions on basic information, history of urinary tract infection, constipation, smoking, history of alcohol consumption, history of coffee/strong tea drinking, history of carbonated beverage drinking, redundant prepuce, phimosis, holding urine, chronic insomnia, self-rating anxiety scale (SAS), quality of life score (QoL), and social avoidance and distress scale (SADS).The influencing factors of OAB were analyzed with multivariate logistic regression analysis.The subjects were grouped according to whether they had OAB, and the differences in SAS, QoL and SADS between the OAB group and non-OAB group were compared.The impacts of OAB on the anxiety level, quality of life, and social interaction were analyzed with multiple linear regression analysis. Results: The overall prevalence rate of OAB was 4.9% (244/5018).Multivariate logistic regression analysis showed that the history of urinary tract infection (OR=0.177), constipation (OR=0.636), smoking (OR=0.582), alcohol consumption (OR=0.685), coffee/strong tea drinking (OR=0.387), carbonated beverage drinking (OR=0.631), redundant prepuce (OR=0.673), phimosis (OR=0.311), urine holding (OR=0.593), and chronic insomnia (OR=0.256) were influencing factors for the occurrence of OAB (P＜0.05).The OAB group had higher SAS score [(41.18±6.54) vs. (38.61±6.36)], QoL score [(3.65±1.20) vs. (2.79±0.95)], social avoidance score [(6.25±1.86) vs. (5.86±1.51)], social distress score [(6.27±1.59) vs. (5.97±1.32)], and total SADS score [(12.51±2.35) vs. (11.84±2.01)] than the non-OAB group (P＜0.05).The results of multiple linear regression analysis showed that OAB could independently affect the scores of QoL, SAS, and SADS.The OAB group had higher scores of QoL, SAS, and SADS compared with the non-OAB group (P＜0.001). Conclusion: History of urinary tract infection, constipation, smoking, alcohol consumption, coffee/strong tea drinking, carbonated beverage drinking, redundant prepuce, phimosis, urine holding, and chronic insomnia are influencing factors for the occurrence of OAB in male college students.Moreover, OAB has negative impacts on their mental health, quality of life, and social interaction.

BACKGROUND: Disease-modifying therapies have been approved for the treatment of relapsing multiple sclerosis (RMS). The present study aims to examine the safety of teriflunomide in Chinese patients with RMS. METHODS: This non-randomized, multi-center, 24-week, prospective study enrolled RMS patients with variant (c.421C>A) or wild type ABCG2 who received once-daily oral teriflunomide 14 mg. The primary endpoint was the relationship between ABCG2 polymorphisms and teriflunomide exposure over 24 weeks. Safety was assessed over the 24-week treatment with teriflunomide. RESULTS: Eighty-two patients were assigned to variant ( n  = 42) and wild type groups ( n  = 40), respectively. Geometric mean and geometric standard deviation (SD) of pre-dose concentration (variant, 54.9 [38.0] μg/mL; wild type, 49.1 [32.0] μg/mL) and area under plasma concentration-time curve over a dosing interval (AUC tau ) (variant, 1731.3 [769.0] μg∙h/mL; wild type, 1564.5 [1053.0] μg∙h/mL) values at steady state were approximately similar between the two groups. Safety profile was similar and well tolerated across variant and wild type groups in terms of rates of treatment emergent adverse events (TEAE), treatment-related TEAE, grade ≥3 TEAE, and serious adverse events (AEs). No new specific safety concerns or deaths were reported in the study. CONCLUSION: ABCG2 polymorphisms did not affect the steady-state exposure of teriflunomide, suggesting a similar efficacy and safety profile between variant and wild type RMS patients. REGISTRATION NCT04410965, https://clinicaltrials.gov .
Humans ; Crotonates/adverse effects* ; Toluidines/adverse effects* ; Nitriles ; Hydroxybutyrates ; Female ; Male ; Adult ; ATP Binding Cassette Transporter, Subfamily G, Member 2/genetics* ; Middle Aged ; Multiple Sclerosis, Relapsing-Remitting/genetics* ; Prospective Studies ; Young Adult ; Neoplasm Proteins/genetics* ; East Asian People

The elevated polyamines, amine-rich molecules with diverse functions in pathophysiology processes, are implicated in contributing to tumorigenesis and progression. Whether and how they affect the efficacy of chemotherapy is incompletely understood. Our screening assays reveal that the supplement with a low dose of spermidine (Spd), one of the polyamines, enhances ferroptosis in prostate cancer cells as evidenced by increased lipid peroxidation and intracellular Fe²⁺ levels in vitro. Combination treatment with Spd and a low dose of ferroptosis inducer erastin synergistically augments anti-tumor efficacy with undetectable toxicity in mice. Analysis of RNA-seq data indicates that heme oxygenase 1 (HMOX1), an enzyme that catalyzes the cleavage of heme to release Fe²⁺, is significantly upregulated in response to Spd and erastin cotreatment. Spd mediated the hypusine modification of the eukaryotic initiation factor 5A (EIF5A) promotes the translation of the nuclear factor erythroid 2-related factor 2 (NRF2), subsequently leading to elevation of HMOX1. Moreover, Spd and erastin significantly inhibit proteasome activity which results in a decrease in proteasomal degradation of NRF2, although many proteasome-related genes are induced either by Spd or Spd plus erastin. Thus, in addition to its pro-oncogenic activity, the supplement of Spd improves antitumor activity in combination with ferroptosis inducers and offers an optional approach to cancer treatment.

Type 2 diabetes mellitus(T2DM)is a metabolic disease characterized by insulin resistance,and is one of the most common chronic non-communicable diseases worldwide.In the field of traditional Chinese medicine(TCM),yang deficiency causing diabetes is one of the important pathogenetic mechanisms of T2DM and contributes to the core pathological basis of insulin resistance.Guided by the theory of yang deficiency causing diabetes,this paper reviewed the relevant domestic literature issued in recent years,sorted out western medical pathogenesis and treatment for insulin resistance in T2DM,TCM theory of yang deficiency causing diabetes and its clinical application,and the clinical efficacy of TCM for the treatment of insulin resistance,and then explored the applicability of theory of yang deficiency causing diabetes for TCM treatment of insulin resistance in T2DM.It is concluded that TCM treatment for insulin resistance in T2DM based on the theory of yang deficiency causing diabetes has significant efficacy and advantages,for it realizes the integration of advantages of TCM and western medicine and achieves the synergistic actions through keeping the scientific nature and standardization of western medicine and by maintaining the advantages of holism and individualization of TCM treatment.TCM treatment for insulin resistance is effective on improving insulin signal transduction,insulin secretion function and other related metabolic abnormalities indicators through multiple pathways and targets,thus to improve the health status of the body.TCM treatment for insulin resistance exerts good safety and tolerance,and can reduce the incidence of adverse reactions caused by western medicine.However,the research on TCM treatment for insulin resistance still has the insufficiencies such as low quality of clinical trials,unclear therapeutic mechanism,and lack of innovation and pioneering.Further relevant research needs to be carried out in-depth,so as to provide a scientific basis for TCM to play a greater role in preventing and treating metabolic diseases.

Objective: To investigate whether TYRO protein tyrosine kinase-binding protein (TYROBP) affects the progression of diabetic kidney disease (DKD) through the extracellular signal-regulated kinase ( ERK) pathway. Methods: Key genes in DKD were identified through bioinformatics analysis . Immunohistochemical staining and quantitative real-time PCR (qPCR) were used to validate the expression levels of TYROBP in a DKD mouse model and high glucose-stimulated NRK-52E cells . NRK-52E cell models with stable TYROBP overexpression/knockdown and their corresponding empty vector (ev) /scrambled sequence (ss) controls were established via lentiviral trans- fection . Cells were treated with 5 . 5 mmol/L or 30. 0 mmol/L glucose for 72 hours to mimic normal glucose (NG) and high glucose ( HG) conditions , respectively. High glucose medium containing 3 . 5 μmol/L FR180204 was used for ERK inhibitor intervention . The experiment included seven groups : ev + NG , ev + HG , oe-TYROBP + HG , ss + NG , ss + HG , sh-TYROBP + HG , and sh-TYROBP + HG + ERK inhibitor. Western blot was used to de- tect the expression levels of phosphorylated ERK/total ERK (p-ERK/ERK) , apoptosis-related proteins B-cell lym- phoma-2 (Bcl-2) and Bcl-2-associated X protein ( Bax) , and epithelial-mesenchymal transition ( EMT)-related proteins E-cadherin and α-smooth muscle actin ( α-SMA) . Tetramethylrhodamine ethyl ester (TMRE) staining and Annexin V-fluorescein isothiocyanate/propidium iodide (Annexin V-FITC/PI) flow cytometry were performed to as- sess mitochondrial membrane potential and apoptosis levels . Results: Bioinformatics analysis identified TYROBP as a key gene in DKD . In vivo and in vitro validation showed increased TYROBP mRNA levels in DKD models . The results from the HG model indicated that , compared to the ev + NG/ss + NG group , the ev + HG/ss + HG group demonstrated increased p-ERK/ERK expression , reduced mitochondrial membrane potential , elevated apoptosis , and enhanced EMT. In TYROBP-perturbed NRK-52E cells , compared to the ev + HG group , the oe-TYROBP + HG group showed decreased p-ERK/ERK expression (P < 0. 01) , increased mitochondrial membrane potential (P < 0. 05) , reduced apoptosis (P < 0. 001) , and attenuated EMT; whereas compared to the ss + HG group , the sh- TYROBP + HG group exhibited increased p-ERK/ERK expression ( P < 0. 001) , decreased mitochondrial mem- brane potential (P < 0. 01) , elevated apoptosis (P < 0. 001) , and enhanced EMT. Furthermore , compared to the sh-TYROBP + HG group , the sh-TYROBP + HG + ERK inhibitor group displayed reduced p-ERK/ERK expression (P < 0. 01) , increased mitochondrial membrane potential ( P < 0. 001) , decreased apoptosis ( P < 0. 001) , and suppressed EMT. Compared with the scrambled sequence control + high glucose group , the TYROBP knockdown + high glucose group showed elevated p-ERK/ERK expression ( P < 0. 001) , reduced mitochondrial membrane potential (P < 0. 01) , increased apoptosis level (P < 0. 001) , and enhanced EMT. Compared with the TYROBP knockdown + high glucose group , the TYROBP knockdown + high glucose + ERK inhibitor group demonstrated decreased p-ERK/ERK expression (P < 0. 01) , restored mitochondrial membrane potential (P < 0. 001) , reduced apoptosis level (P < 0. 001) , and suppressed EMT. Conclusion TYROBP may regulate the ERK signaling path- way to modulate apoptosis- and EMT-related proteins , thereby influencing mitochondrial membrane potential , apop- tosis , and EMT in renal tubular epithelial cells and contributing to DKD progression .

Background The high-quality development of manufacturing in China has spurred industrial transformation and upgrading, placing higher demands on the skills of employees in the electronic manufacturing industry. This situation may induce psychological health problems such as job burnout and depressive symptoms in the employees, and also lead to insomnia, which has become a public health problem that urgently needs attention and solution. Objective To investigate the relationship between job burnout, depressive symptoms, and insomnia among employees in the electronic manufacturing industry. Methods A total of 3034 employees from four electronic manufacturing companies in Beijing City, Shanghai City, and Guangdong Province were selected using judgment sampling from September to November 2019. The Maslach Burnout Inventory-General Survey, Patient Health Questionnaire-9, and Self-Administered Sleep Questionnaire were used to collect data. The correlation between job burnout, depressive symptoms, and insomnia was evaluated by hierarchical regression. Results A total of 3034 survey questionnaires were distributed, and 2614 valid questionnaires were collected, with a response effectiveness rate of 86.2%. The reporting rates of job burnout, depressive symptoms, and insomnia among employees in the electronic manufacturing industry were 47.2%, 19.5%, and 29.1%, respectively. The reporting rates of insomnia of employees in the job burnout group and depressive symptoms group were higher than those in the non-job burnout group and non-depressive symptoms group (35.3% vs. 23.6%, 47.2% vs. 24.7%, P＜0.001). The results of hierarchical regression showed that job burnout explained 2.8% of the variation of insomnia (P<0.001), and the inclusion of depressive symptoms explained 1.2% of the variation of insomnia (P<0.001). Conclusion Job burnout and depressive symptoms could both affect insomnia of employees in the electronic manufacturing industry.