Objective To explore the predictive effect of serum 25-hydroxyvitamin D3 [25(OH)D3] and blood lipid metabolism indexes on the occurrence of osteoporosis in type 2 diabetes mellitus (T2DM). Methods Totally 98 patients with T2DM in the hospital from January 2022 to January 2024 were classified into osteoporosis group (38 cases) and non-osteoporosis group (60 cases) by means of concurrent osteoporosis status. The levels of serum 25(OH)D3 and blood lipid metabolism indexes [high density lipoprotein (HDL), total cholesterol (TC), triglyceride (TG), low density lipoprotein (LDL), VLDL] were measured in study subjects. The association of serum 25(OH)D3 and blood lipid metabolism indexes with osteoporosis was explored by Logistic regression analysis. The predictive value of serum 25(OH)D3 and blood lipid metabolism indexes on osteoporosis was analyzed by receiver operating characteristic curve (ROC). Results Serum 25(OH)D3 and HDL levels in the osteoporosis group were lower while TG and LDL levels were higher than those in the non-osteoporosis group (P<0.05). The differences in the levels of TC and VLDL were insignificant between groups (P>0.05). After logistic regression analysis, the levels of serum 25(OH)D3, HDL, TG and LDL were closely related to the occurrence of osteoporosis (P<0.05). ROC curve indicated that the area under the curve (AUC), sensitivity and specificity of combined prediction of osteoporosis by serum 25(OH)D3, HDL, TG, and LDL were 0.943, 92.11% and 85.00%, and the efficiency of combined prediction was better than that of each index alone (P<0.05). Conclusion The levels of serum 25(OH)D3, HDL, TG and LDL in T2DM are closely related to osteoporosis. Early combined monitoring of the indicators can provide reference value for clinical prediction of osteoporosis occurrence in patients with T2DM.

Objective:To investigate whether exosome-derived microRNA (miR)-877-5p can affect the malignant biological behaviors of glioma cells by regulating transmembrane 4 superfamily member 1 (TM4SF1).Methods:(1) Tumor tissues and corresponding adjacent tissues from 42 patients with glioma who underwent surgical resection in Department of Neurosurgery, the First Affiliated Hospital of Nanyang Medical College from September 2024 to February 2025 were collected. The miR-877-5p and TM4SF1 mRNA expressions in tumor tissues and corresponding adjacent tissues were detected by quantitative reverse transcription polymerase chain reaction (qRT-PCR), and the correlation between miR-877-5p and TM4SF1 mRNA expressions in tumor tissues was analyzed by Pearson correlation. (2) HEB, U87, LN229, and U251 cells at the logarithmic growth phase were cultured and their miR-877-5p and TM4SF1 mRNA expressions were detected by qRT-PCR. Exosomes from U87, LN229, and U251 cells were isolated, and their morphology was observed under a transmission electron microscope; protein expressions of CD9, CD63, tumor susceptibility gene 101 (TSG101), and Calnexin in exosomes were detected by Western blotting. The miR-877-5p expression in exosomes of U87, LN229, and U251 cells was detected by qRT-PCR. The diameter of exosomes from LN229 cells was measured using a Malvern Zetasizer particle size and zeta potential analyzer, and the uptake efficiency of exosomes in LN229 cells was detected by flow cytometry. LN229 cells were divided into a normal control group, a miR-877-5p negative control group, a miR-877-5p mimic group, a miR-877-5p mimic+pcDNA empty vector group, and a miR-877-5p mimic+pcDNA-TM4SF1 group; except for the normal control group, the other groups were transfected with corresponding plasmids through exosomes and cultured for 24 hours; and then, miR-877-5p mRNA expression was detected by qRT-PCR; cell viability was detected by CCK-8 assay, cell apoptosis was detected by flow cytometry, cell invasion was detected by Transwell assay, and TM4SF1, Cyclin D1, Bcl-2 associated X protein (Bax), and matrix metalloproteinase 2 (MMP2) protein expressions and expressions of TM4SF1 downstream pathway proteins phosphorylated protein kinase B (p-AKT) and β-catenin were detected by Western blotting. The targeting relation between miR-877-5p and TM4SF1 was validated using a dual-luciferase reporter assay. A U251 cell experiment was performed for universal verification: U251 cells were divided into a normal control group, a miR-877-5p negative control group, a miR-877-5p mimic group, a miR-877-5p mimic+pcDNA empty vector group, and a miR-877-5p mimic+pcDNA-TM4SF1 group; cell apoptosis was detected by flow cytometry, and TM4SF1 protein expression was detected by Western blotting. (3) Eighteen male BALB/c nude mice were randomly divided into a control group, a miR-877-5p mimic group, and a miR-877-5p mimic+pcDNA-TM4SF1 group, with 6 mice in each group; 100 μL LN229 cell suspension, LN229 cell suspension transfected with miR-877-5p mimic, and LN229 cell suspension transfected with miR-877-5p mimic and pcDNA-TM4SF1 were, respectively, subcutaneously injected into the lateral abdomen of nude mice in these 3 groups. After 28 days of feeding, the mass and volume of the transplanted tumors were measured, and the TM4SF1, Cyclin D1, Bax, and MMP2 protein expressions in the transplanted tumors were detected by Western blotting. Results:(1) Compared with that in the corresponding adjacent tissues, miR-877-5p mRNA expression in the tumor tissues was significantly decreased and TM4SF1 mRNA expression was statistically increased ( P<0.05). Correlation analysis showed that the miR-877-5p and TM4SF1 mRNA expressions in the tumor tissues were negatively correlated ( r=-0.966, P<0.001). (2) Compared with those in the HEB cells, statistically decreased miR-877-5p mRNA expression and increased TM4SF1 mRNA expression in U87, LN229, and U251 cells were noted ( P<0.05). Under the transmission electron microscope, the exosomes in glioma cells were all biconcave disc-shaped and had a complete lipid bilayer membrane structure. Western blotting indicated positive CD9, CD63, and TSG101 protein expressions and negative Calnexin protein expression in the exosomes of glioma cells. Flow cytometry results indicated a relatively high uptake efficiency of exosomes in LN229 cells. Compared with that in the U87 and U251 cells, the miR-877-5p mRNA expression in exosomes of LN229 cells was significantly decreased ( P<0.05). The diameter of exosomes in LN229 cells was 80-150 nm. Compared with the miR-877-5p negative control group, the miR-877-5p mimic group had an increased miR-877-5p mRNA expression, decreased cell survival rate (negative control group: [95.43±0.23]%; miR-877-5p mimic group: [51.24±5.67]%), increased cell apoptosis rate ([3.34±0.22]% vs. [35.24±4.17]%), reduced number of invasive cells ([127.33±13.63] cells per high-power field vs.[59.67±6.87] cells per high-power field), downregulated TM4SF1, Cyclin D1 and MMP2 protein expressions, upregulated Bax protein expression, and decreased p-AKT and β-catenin protein expressions, with significant differences ( P<0.05). Compared with the miR-877-5p mimics+pcDNA empty vector group, the miR-877-5p mimic+pcDNA-TM4SF1 group had a decreased miR-877-5p expression, increased cell survival rate (miR-877-5p mimics+pcDNA empty vector group: [56.27±5.24]%; miR-877-5p mimic+pcDNA-TM4SF1 group[75.31±8.13]%), decreased cell apoptosis rate ([36.27±4.42]% vs. [15.37±1.73]%), increased number of invasive cells ([62.67±6.14] cells per high-power field vs. [95.50±10.58] cells per high-power field), upregulated TM4SF1, Cyclin D1 and MMP2 protein expressions, decreased Bax protein expression, and upregulated p-AKT and β-catenin protein expressions, with significant differences ( P<0.05). Dual-luciferase assay results showed that in the plasmids carrying wild-type TM4SF1 sequence, the luciferase activity in the miR-877-5p mimics group was significantly lower than that in the miR-877-5p negative control group ( P<0.05); in the plasmids carrying the mutant TM4SF1 sequence, no significant change in the luciferase activity was noted between the miR-877-5p negative control group and miR-877-5p mimic group ( P>0.05). Universal verification results: in U251 cells, compared with the miR-877-5p negative control group, the miR-877-5p mimic group had a significantly increased cell apoptosis rate and a statistically decreased TM4SF1 protein expression ( P<0.05); compared with the miR-877-5p mimic+pcDNA empty vector group, the miR-877-5p mimic+pcDNA-TM4SF1 group showed significantly decreased apoptosis rate and statistically increased TM4SF1 protein expression ( P<0.05). (3) Compared with the normal control group, the miR-877-5p mimic group had statistically reduced tumor mass and volume, significantly decreased TM4SF1, Cyclin D1 and MMP2 protein expressions, and significantly increased Bax protein expression ( P<0.05). Compared with the miR-877-5p mimic group, the miR-877-5p mimic+pcDNA-TM4SF1 group had significantly increased tumor mass and volume, statistically increased TM4SF1, Cyclin D1 and MMP2 protein expressions, and statistically decreased Bax protein expression ( P<0.05). Conclusion:Exosome-derived miR-877-5p may inhibit the proliferative and invasive capacities of glioma cells and promote cell apoptosis by targetedly inhibiting the TM4SF1 expression, thereby exerting an anti-tumor effect.

Objective To investigate the disparities in the activities of daily living(ADL)among older adults living in urban and rural areas of Sichuan Province,China and the influencing factors,and to provide a basis for promoting the health of older adults and formulating relevant policies.Methods Using data from the Seventh Health Services Survey of Sichuan Province,we enrolled 7 369 older adults from urban and rural areas and analyzed their ability to perform ADL and the relevant influencing factors.All participants were aged 60 years or older.Chi-square tests and logistic regression were performed to identify the influencing factors.Results The ADL impairment rate among older adults living in urban areas of Sichuan Province was 17.7％,which was higher than the rate of 13.8％among older adults living in rural areas.According to the results of logistic regression analysis,age≥80 years(odds ratio[OR]=3.725;95％CI,2.460-5.639),accidental injuries(OR=2.375;95％CI,1.597-3.532),and good sleep quality(OR=0.420,95％CI:0.289-0.612)were factors influencing ADL among older adults living in urban areas,while age ≥ 80 years(OR=1.867;95％CI,1.459-2.390),being married(OR=0.805;95％CI,0.664-0.976),accidental injuries(OR=1.936;95％CI,1.564-2.397),and participation in social activities(OR=0.417;95％CI,0.352-0.495)were factors influencing ADL among older adults living in rural areas.Conclusion There are differences in ADL impairment rates and the relevant influencing factors between urban and rural older adults in Sichuan Province.These findings underscore the need to consider urban-rural differences when adopting relevant policies and measures.

Objective:To summarize the clinical features, laboratory findings, treatment and prognosis of children confirmed as Mycoplasma pneumoniae-induced rash and mucositis (MIRM) in children. Methods:This retrospective study concluded 6 children diagnosed as MIRM in Department of Gastroenterology and Infectious Diseases, Shanghai Children′s Hospital, School of Medicine, Shanghai Jiao Tong University from August 2023 to April 2024. This paper described the characteristics of MIRM and analyzed the therapeutic strategy and prognosis.Results:A total of 6 children were diagnosed as MIRM including 2 boys and 4 girls with an age of onset was 6.4 (3.1, 7.5) years. Among the 6 patients, 4 patients had oral mucosal involvement among whom 2 showed crusting of the lips. Four patients had ocular involvement manifesting as conjunctival congestion and increased secretion. All patients presented with skin lesions, manifesting as target-shaped damage in 4 cases, herpes herpetiformis in 1 case and purpura-like rash in 1 case. Serological tests for Mycoplasma pneumoniae IgM and Mycoplasma pneumoniae nucleic acid test were positive in all 6 cases. Two cases received intravenous immunogloblin infusion combined with methylprednisolone, monotherapy of methylprednisolone in 4 cases. The course of glucocorticoids was 1-7 weeks, and the initial dose was 2-4 mg/(kg·d), which was gradually reduced according to the rash. The children were followed up for 3 to 9 months, no case suffered from long term ocular or cutaneous complications or recurrence of rash. All cases had good prognosis. Conclusions:Children diagnosed as MIRM present with mild symptoms and usually have good prognosis with early identification and appropriate intervention. Individualized therapy should be applied based on the severity of skin involvement.

Objective:To address large-scale nonlinear programming challenges in optimizing prognosis-guided intensity-modulated radiation therapy (IMRT) plans, to propose gradient-enhanced random contrastive interaction particle swarm optimization (GradRCIPSO). This gradient-enhanced swarm intelligence algorithm aims to enable global optimization of prognostic treatment plans in clinically efficient scenarios.Methods:The core concept of GradRCIPSO lied in achieving rapid global convergence by allowing particles to learn both swarm interaction and gradient information. Specifically, the interaction information was obtained from elite individuals in the swarm, enabling the particles to efficiently search the entire solution space, whereas the gradient information represents the direction of the steepest descent, enabling the particles to quickly explore the current neighborhood. To assess the effectiveness of the methodology, the IMRT plans for 10 cases of non-small cell lung cancer (NSCLC) were selected in this study. They were compared with the GradRCIPSO-generated prognosis-guided IMRT plans. Moreover, the interior-point method, sequential quadratic programming, active set, gradient descent method, and random contrastive interaction particle swarm optimization (RCIPSO) were employed as optimization engines and compared with GradRCIPSO in terms of optimization efficiency and accuracy.Results:GradRCIPSO successfully generated clinically viable prognosis-guided IMRT plans with comparable dosimetric statistics to original plans, while significantly reducing predicted total radiotherapy risk from 1.22(0.84, 1.51) to 0.93(0.80, 1.29) ( z=2.81, P<0.01). It demonstrated superior accuracy over the above four gradient-based method ( z=2.80-2.81, P<0.01) and achieved threefold acceleration versus RCIPSO while maintaining equivalent solution quality( P>0.05). Conclusions:The proposed GradRCIPSO demonstrates high feasibility and performance in optimizing prognosis-guided IMRT plans, laying the technical foundation for the broad clinical application of prognosis-guided IMRT plans for lung cancer.

Objective To explore the application effect of nursing intervention based on empow-erment theory in treatment of facial photoaging with fractional ablative fractional laser.Methods A total of 90 patients with facial photoaging who underwent fractional ablative fractional laser treatment were selected and divided into control group and observation group according to random number table method,with 45 cases in each group.The control group received routine nursing intervention,while the observation group received nursing intervention based on empowerment theory.The skin condi-tion,the incidence of adverse reactions,psychological state[Self-Rating Anxiety Scale(SAS),Self-Rating Depression Scale(SDS)]scores,and quality of life[Dermatology Life Quality Index(DLQI)]scores were compared between the two groups.Results After intervention,the percentages of skin characteristics such as enlarged facial pores,wrinkles,and spots in the observation group were higher than those in the control group;the incidence of adverse reactions in the observation group was lower than that in the control group(8.89％ versus 24.44％);the SAS scores,SDS scores,and total DLQI scores in the observation group were lower than those in the control group,with statistically sig-nificant differences(P＜0.05).Conclusion Nursing intervention based on empowerment theory can effectively improve the facial skin condition of patients with facial photoaging treated with fraction-al ablative fractional laser,reduce the incidence of adverse reactions,alleviate negative emotions,and enhance quality of life.

Objective:To develop a treatment-related quality of life scale for Chinese patients with multiple myeloma (MM) and to test its reliability and validity.Methods:The initial scale was constructed through a literature search, Delphi expert correspondence, and cognitive testing. This study conducted a preliminary survey of 379 patients with MM and a formal survey of 865 patients from the hematology departments of 155 hospitals nationwide from February 2024 to March 2024. The final scale was obtained after conducting item analysis and reliability and validity tests on the initial scale.Results:The constructed scale contains 36 items covering six domains: physiological, psychological, social, treatment side effects, general health, and others. In the preliminary survey, the Cronbach’s alpha coefficient of each item ranged from 0.597 to 0.939, and the test-retest reliability was 0.747 ( P<0.001). Exploratory factor analysis extracted eight common factors with a cumulative variance contribution of 60.058%. In the formal survey, the Cronbach’s alpha coefficient of each item ranged from 0.484 to 0.930, and the test-retest reliability was 0.835 ( P<0.001). Confirmatory factor analysis revealed a comparative fit index of 0.750, a root-mean-square error of approximation of 0.090, and a root-mean-square residual of 0.067. Conclusion:The treatment-related quality of life scale for Chinese patients with MM designed in this study exhibited good reliability and validity, reflecting the impact of treatment on the quality of life of patients. This scale can provide a reference to clinicians for assessing the disease status of patients.

Objective:To analyze the prospective associations between liver biomarkers and mortality among Chinese middle-aged and elderly populations and to evaluate the mortality risk predictive value.Methods:A total of 22 758 participants from the 3 rd resurvey of the China Kadoorie Biobank were included. Cox proportional hazard models were used to analyze the prospective associations of 5 liver biomarkers with mortality. These liver biomarkers included two liver imaging biomarkers (liver fat attenuation parameter, liver stiffness measurement) and three serum liver enzyme biomarkers [gamma-glutamyl transferase (GGT), ALT, and AST]. Restricted cubic spline was used to assess the nonlinear associations between biomarkers and mortality. The area used the receiver operating characteristic curve (AUC) to evaluate the predictive ability of the models after incorporating liver biomarkers into traditional prediction models for mortality. Results:The mean age of the participants was (65.2±9.1) years, with a median follow-up of 1.5 years, during which 307 deaths occurred. Compared to individuals without hepatic steatosis, those with severe hepatic steatosis had a 79% higher risk of mortality, with a HR of 1.79 (95% CI: 1.06-3.03). Compared to individuals without hepatic fibrosis, those with advanced fibrosis and cirrhosis had higher mortality risks of 48% and 91%, respectively (both P<0.05). For each standard deviation increase in GGT, the mortality risk increased by 10% ( HR=1.10, 95% CI: 1.05-1.15), with the positive association plateauing at higher GGT levels. AST exhibited a U-shaped association with mortality risk. The AUC of the prediction model adding liver biomarkers into traditional prediction factors was 0.718 (95% CI: 0.679-0.757), with an increase of 0.030 ( P<0.001) compared with the traditional model. Conclusions:Severe hepatic steatosis, higher levels of hepatic fibrosis, and elevated GGT levels are significantly associated with higher mortality risk. AST shows a U-shaped nonlinear association with mortality risk. Incorporating liver biomarkers into traditional risk prediction models enhance the ability to predict mortality.

Objective:To investigate the prospective associations between plasma metabolites and the risks of all-cause and cause-specific mortality among Chinese adults.Methods:This study analyzed plasma metabolomics data from 2 183 healthy adults in the China Kadoorie Biobank (CKB), measured using targeted mass spectrometry. Cox proportional hazards regression models were used to examine the associations between 630 metabolites and the risk of all-cause mortality. Cause-specific hazard regression models evaluated the associations between metabolites and cardiovascular disease (CVD) risks, cancer, and other-cause mortality. Stepwise regression was used to identify key metabolites independently associated with all-cause mortality, and the area under the receiver operating characteristic curve (AUC) was calculated to assess the improvement in predictive performance when these metabolites were added to traditional risk prediction models.Results:The mean age of the participants was (53.2±9.8) years, 65.1% of whom were female. During a median follow-up of 14.5 years, 231 deaths occurred. A total of 44 metabolites were significantly associated with the risk of all-cause mortality [false discovery rate (FDR)-adjusted P<0.05], primarily including triglycerides, ceramides, and amino acids. Additionally, 29 and 15 metabolites were found to be associated with cancer and other-cause mortality, respectively, but no metabolites were significantly associated with CVD mortality after FDR corrections. Adding 14 metabolites independently associated with all-cause mortality into the traditional prediction model significantly improved its predictive performance. Specifically, incorporating metabolites into the traditional model, which already included laboratory biomarkers, increased the AUC to 0.798 (95% CI: 0.755-0.843), an improvement of 0.088 compared to the traditional model ( P<0.001). Conclusions:Multiple metabolites are significantly associated with mortality risk and can substantially improve the accuracy of mortality risk prediction models. These findings provide new insights into the physiological mechanisms of aging and offer valuable clues for personalized health risk assessment.

Tumor drug resistance is an important problem in the failure of chemotherapy and targeted drug therapy, which is a complex process involving chromatin remodeling. SWI/SNF is one of the most studied ATP-dependent chromatin remodeling complexes in tumorigenesis, which plays an important role in the coordination of chromatin structural stability, gene expression, and post-translation modification. However, its mechanism in tumor drug resistance has not been systematically combed. SWI/SNF can be divided into 3 types according to its subunit composition: BAF, PBAF, and ncBAF. These 3 subtypes all contain two mutually exclusive ATPase catalytic subunits (SMARCA2 or SMARCA4), core subunits (SMARCC1 and SMARCD1), and regulatory subunits (ARID1A, PBRM1, and ACTB, etc.), which can control gene expression by regulating chromatin structure. The change of SWI/SNF complex subunits is one of the important factors of tumor drug resistance and progress. SMARCA4 and ARID1A are the most widely studied subunits in tumor drug resistance. Low expression of SMARCA4 can lead to the deletion of the transcription inhibitor of the BCL2L1 gene in mantle cell lymphoma, which will result in transcription up-regulation and significant resistance to the combination therapy of ibrutinib and venetoclax. Low expression of SMARCA4 and high expression of SMARCA2 can activate the FGFR1-pERK1/2 signaling pathway in ovarian high-grade serous carcinoma cells, which induces the overexpression of anti-apoptosis gene BCL2 and results in carboplatin resistance. SMARCA4 deletion can up-regulate epithelial-mesenchymal transition (EMT) by activating YAP1 gene expression in triple-negative breast cancer. It can also reduce the expression of Ca²⁺ channel IP3R3 in ovarian and lung cancer, resulting in the transfer of Ca²⁺ needed to induce apoptosis from endoplasmic reticulum to mitochondria damage. Thus, these two tumors are resistant to cisplatin. It has been found that verteporfin can overcome the drug resistance induced by SMARCA4 deletion. However, this inhibitor has not been applied in clinical practice. Therefore, it is a promising research direction to develop SWI/SNF ATPase targeted drugs with high oral bioavailability to treat patients with tumor resistance induced by low expression or deletion of SMARCA4. ARID1A deletion can activate the expression of ANXA1 protein in HER2+ breast cancer cells or down-regulate the expression of progesterone receptor B protein in endometrial cancer cells. The drug resistance of these two tumor cells to trastuzumab or progesterone is induced by activating AKT pathway. ARID1A deletion in ovarian cancer can increase the expression of MRP2 protein and make it resistant to carboplatin and paclitaxel. ARID1A deletion also can up-regulate the phosphorylation levels of EGFR, ErbB2, and RAF1 oncogene proteins.The ErbB and VEGF pathway are activated and EMT is increased. As a result, lung adenocarcinoma is resistant to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs). Although great progress has been made in the research on the mechanism of SWI/SNF complex inducing tumor drug resistance, most of the research is still at the protein level. It is necessary to comprehensively and deeply explore the detailed mechanism of drug resistance from gene, transcription, protein, and metabolite levels by using multi-omics techniques, which can provide sufficient theoretical basis for the diagnosis and treatment of poor tumor prognosis caused by mutation or abnormal expression of SWI/SNF subunits in clinical practice.