ObjectiveTo explore the role of the histone deacetylase Sirtuin-1 （SIRT1）/p53 signaling pathway in promoting apoptosis of non-small cell lung cancer cells （NSCLC） induced by the co-stimulatory molecule B7 homolog 3 （B7-H3）. MethodsThe GEPIA 2 platform was used for survival analysis of NSCLC patients based on B7⁃H3 gene expression levels. The Gene Enrichment Analysis （GSEA） method was used to analyze the enrichment characteristics of B7⁃H3 molecules in the gene set of cell apoptosis. In the non-small cell lung cancer A549 cell line， B7⁃H3 was knocked down， and the protein expression levels of SIRT1 and p53 were detected by Western blot. B7⁃H3 was overexpressed in A549 cells and the apoptosis rate was analyzed by flow cytometry after Annexin V/PI double staining. Overexpression of B7⁃H3 and knockdown of SIRT1 were performed in A549 cell line. The expression levels of p53 and apoptosis-related proteins B-cell lymphoma/leukemia-2 （Bcl-2） and Bcl-2-associated X protein （Bax） were detected respectively by Western blot. Cell apoptosis rate was analyzed by flow cytometry after Annexin V/PI double staining. ResultsThe overall survival of the B7-H3 high-expression group was significantly lower than that of the low-expression group （P<0.01）. B7-H3 was significantly enriched in the cell apoptosis signaling pathway and the p53 signaling pathway （P<0.05）. Compared with the control group， the expression of SIRT1 was significantly downregulated， and p53 was significantly upregulated in the B7⁃H3 knockdown group （both P<0.001）. Overexpression of B7-H3 significantly up-regulated SIRT1 protein expression （P<0.05）， down-regulated p53 expression （P<0.01）， and markedly increased the Bcl-2/Bax ratio of apoptosis-related proteins （P<0.001）. The results of Annexin V/PI double staining showed that the apoptosis rate of A549 cells with overexpressed B7⁃H3 decreased （the apoptosis rate of the control group was 26.72%±4.13%， while that of the B7⁃H3 overexpression group was 13.87%±0.82%； P<0.01）. In B7-H3-overexpressing cell lines， SIRT1 knockdown significantly reversed apoptosis （P<0.05）， up-regulated p53 protein expression （P<0.001）， and markedly reduced the Bcl-2/Bax ratio （P<0.001）. ConclusionB7-H3 molecule inhibits the apoptosis of non-small cell lung cancer cells via the SIRT1/p53 signaling pathway.

Objective To investigate the predictive value of Caprini model score combined with neutrophil/lymphocyte ratio(NLR)for deep vein thrombosis in elderly patients with intertrochanteric fracture.Methods A total of 70 elderly patients with intertrochanteric femoral fractures who received surgical treatment in the hospital from November 2022 to May 2024 were prospectively selected as the study subjects.The enrolled patients were divided into occurrence group and non-occurrence group according to whether DVT was complicated during postoperative hospitalization.,general data,surgery-related indexes were compared between the two groups,multivariate Logistic regression analysis was used to identify the risk factors affecting postoperative DVT.The efficacy of Caprini model score combined with NLR in predicting postoperative DVT was evaluated by receiver operating characteristic curve(ROC).Results Compared with the non-occurrence group,the Caprini model score,NLR,combined diabetes rate,D-dimer(D-D)and hypersensitive C-reactive protein(hs-CRP)levels in the occurrence group were higher(P＜0.05),the injury-hospital admission time was longer(P＜0.05),the intraoperative blood loss was greater(P＜0.05),and the platelet-derived growth factor(PDGF)was lower(P＜0.05).Logistic multivariate regression analysis results show that Caprini model has high score(OR=2.044,95％CI:1.825～2.764),high NLR(OR=2.008,95％CI:1.840～2.696),combined with diabetes(OR=1.834,95％CI:1.726～2.463),long duration of injury-hospital admission(OR=1.828,95％CI:1.625～2.531),large intraoperative blood loss(OR=1.851,95％CI:1.682～2.421),high D-D level(OR=1.910,95％CI:1.771～2.605)and low PDGF level(OR=1.934,95％CI:1.706～2.568)were risk factors for deep vein thrombosis in elderly patients with intertrochanteric fracture.ROC curve results show that the sensitivity and AUC of Caprini model score combined with NLR in predicting postoperative deep vein thrombosis in elderly patients with intertrochanteric fracture are 90.50％and 0.902,respectively,these indexes are higher than Caprini model score(87.20％,0.869)and NLR(84.60％,0.848).Conclusion Both Caprini model score and NLR are higher in elderly patients with DVT after operation,and Caprini model score combined with NLR is more effective in predicting DVT after operation.

Objective To investigate the predictive value of Caprini model score combined with neutrophil/lymphocyte ratio(NLR)for deep vein thrombosis in elderly patients with intertrochanteric fracture.Methods A total of 70 elderly patients with intertrochanteric femoral fractures who received surgical treatment in the hospital from November 2022 to May 2024 were prospectively selected as the study subjects.The enrolled patients were divided into occurrence group and non-occurrence group according to whether DVT was complicated during postoperative hospitalization.,general data,surgery-related indexes were compared between the two groups,multivariate Logistic regression analysis was used to identify the risk factors affecting postoperative DVT.The efficacy of Caprini model score combined with NLR in predicting postoperative DVT was evaluated by receiver operating characteristic curve(ROC).Results Compared with the non-occurrence group,the Caprini model score,NLR,combined diabetes rate,D-dimer(D-D)and hypersensitive C-reactive protein(hs-CRP)levels in the occurrence group were higher(P＜0.05),the injury-hospital admission time was longer(P＜0.05),the intraoperative blood loss was greater(P＜0.05),and the platelet-derived growth factor(PDGF)was lower(P＜0.05).Logistic multivariate regression analysis results show that Caprini model has high score(OR=2.044,95％CI:1.825～2.764),high NLR(OR=2.008,95％CI:1.840～2.696),combined with diabetes(OR=1.834,95％CI:1.726～2.463),long duration of injury-hospital admission(OR=1.828,95％CI:1.625～2.531),large intraoperative blood loss(OR=1.851,95％CI:1.682～2.421),high D-D level(OR=1.910,95％CI:1.771～2.605)and low PDGF level(OR=1.934,95％CI:1.706～2.568)were risk factors for deep vein thrombosis in elderly patients with intertrochanteric fracture.ROC curve results show that the sensitivity and AUC of Caprini model score combined with NLR in predicting postoperative deep vein thrombosis in elderly patients with intertrochanteric fracture are 90.50％and 0.902,respectively,these indexes are higher than Caprini model score(87.20％,0.869)and NLR(84.60％,0.848).Conclusion Both Caprini model score and NLR are higher in elderly patients with DVT after operation,and Caprini model score combined with NLR is more effective in predicting DVT after operation.

Objective:To investigate the efficacy of arthroscopic ligament augmentation repair in the treatment of chronic lateral ankle instability.Methods:The clinical data of 65 patients with chronic lateral ankle instability who received treatment at Shangluo Central Hospital from October 2019 to October 2022 were retrospectively analyzed. The clinical data were divided into three groups based on treatment methods: the mini-open group ( n = 15), in which patients underwent arthroscopy-assisted small incision lateral ligament repair; the arthroscopy group ( n = 15), in which patients received total ankle arthroscopic ligament augmentation repair; and the non-surgical group ( n = 35), in which patients were treated conservatively. The American Orthopedic Foot and Ankle Score (AOFAS) value, the Tegner Activity Scale (TAS) score, Visual Analog Scale (VAS) score, the time to achieve full weight-bearing, and the time to return to sports were compared among all groups. Results:After treatment, AOFAS value and the TAS score increased in all three groups compared with pre-treatment levels, while the VAS value decreased in all groups. All differences were statistically significant ( t = 6.53, 7.45, 6.58, 6.50, 7.62, 6.52, 6.80, 7.50, 6.49, all P < 0.01). There were no significant differences in AOFAS value, TAS score, and VAS score among the three groups (all P > 0.05). The time to achieve full weight-bearing in the arthroscopy group was 6.6 (5.5, 9.0) weeks, which was shorter than the 7.4 (6.0, 9.0) weeks in the mini-open group and the 9.4 (7.6, 12.0) weeks in the non-surgical group. These differences were statistically significant ( H = 7.98, P = 0.001). The proportion of patients returning to sports in the arthroscopy group was 80% (12/15), which was higher than the 66% (10/15) in the mini-open group and the 28% (10/35) in the non-surgical group. These differences were statistically significant ( χ2 = 30.78, P = 0.025). The time to return to sports in the arthroscopy group was 12.1 (9.5, 15.0) weeks, which was shorter than the 14.6 (12.0, 18.2) weeks in the mini-open group and the 16.1 (13.2, 19.0) weeks in the non-surgical group. These differences were statistically significant ( H = 8.90, P = 0.001). Conclusions:Ankle arthroscopic ligament augmentation repair for the treatment of chronic lateral ankle instability is safe and shows better clinical efficacy, making it a viable option for clinical practice.

Objective:To explore the safety and long-term efficacy of transvaginal reconstructive pelvic surgery (TVRPS) in ≥70-year-old women with severe pelvic organ prolapse (POP).Methods:A single-center, prospective cohort study was conducted on 343 elderly women patients with severe POP who received TVRPS at the Fourth Medical Center, Chinese PLA General Hospital, Medical School of Chinese PLA from March 2007 to September 2024. There were 297 cases (86.6%, 297/343) of Ⅲ degree and 46 cases (13.4%, 46/343) of Ⅳ degree prolapse respectively. Among them, anterior pelvic prolapse accounted for 80.8% (277/343), and those with prolapse in two or more sites accounted for 30.0% (103/343). The age was (74.2±3.4) years (range: 70 to 89 years old). There were 300 cases (87.5%, 300/343) with more than one internal medicine disease. Preoperative general conditions were assessed using American Society of Anesthesiologists physical status classification system (ASA) and American College of Surgeons National Surgical Quality Improvement Program-frailty index (ACS NSQIP-FI). TVRPS surgeries included transvaginal hysterectomy, salpingooophorectomy, high uterosacral ligament suspension, sacrospinous ligament fixation, native tissue and mesh repair of the anterior and posterior vaginal walls, mid-urethral sling for anti-urinary incontinence, and levator anal muscle folding suture and perineal repair. Perioperative complications were evaluated using Clavien-Dindo classification system. The objective effect of TVRPS was determined based on pelvic organ prolapse quantification system (POP-Q), and the subjective results were evaluated using pelvic floor distress inventory-short form 20 (PFDI-20), pelvic floor impact questionnaire-short form 7 (PFIQ-7) and patient global impression of improvement (PGI-I).Results:All patients had a preoperative ASA grade of ≤gradeⅡ, and ACS NSQIP-FI score of ≤0.27. All patients safely and successfully underwent all TVRPS surgeries. The operation time was (154.2±43.2) minutes. The perioperative morbidity and mortality rate were 0.6% (2/343) and 0 (0/343) respectively. None of the patient needed blood transfusion. The follow-up time was (7.5±4.3) years, with the longest being 17 years. Thirty-four cases (9.9%, 34/343) were lost to follow-up, and 22 cases (6.4%, 22/343) died of internal diseases during the follow-up period. The point values of Aa, Ba, C, Ap and Bp in the POP-Q system were significantly decreased after the operation (all P<0.01), the genital hiatus was significantly shortened (all P<0.01), and the perineal body was significantly elongated (all P<0.01). The scores of PFDI-20 and PFIQ-7 were significantly lower than those before the operation (all P<0.01). There were 332 cases (96.8%, 332/343) with an overall symptom impression improvement score of PGI-I≤2. Conclusion:The results on 343 elderly women with severe POP aged an average of 74.2 years show that for elderly POP patients who still have the desire to preserve the vagina and do not meet the conditions for colpocleisis, as long as there is a comprehensive understanding and strict evaluation of the overall condition before the operation, TVRPS is a safe, feasible and long-lasting therapeutic procedure.

Background/Aims: Obesity is associated with several gastrointestinal (GI) disorders and has been identified as a potential risk factor for various GI symptoms. Bowel frequency is an important indicator of bowel function. However, the causal link between obesity and gastrointestinal motility remains uncertain. This study aims to determine the causal effect of overall and central obesity on stool frequency. Methods: Four obesity-related anthropometric indicators–body mass index, body fat percentage, waist circumference (WC), and waist-tohip ratio (WHR)–were investigated. Individual-level baseline information from the UK Biobank was used to explore observational associations between obesity and stool frequency. Additionally, summary-level data from published genome-wide association studies were subjected to two-sample Mendelian randomization (MR) analyses to examine causal associations. Results: For all 4 indicators of obesity, higher levels of obesity were associated with more frequent bowel movements after adjusting for demographic characteristics, lifestyle, and dietary factors. After rigorous screening, 482 body mass index single nucleotide polymorphisms (SNPs), 7 body fat percentage SNPs, 48 WC SNPs, and 287 WHR SNPs were identified as instrument variables for MR analysis. The MR results were generally consistent with observational findings, proving that the associations observed in the overall obesity indicators were causal. For central obesity, the association between WHR and stool frequency remained consistent in both analysis phases, whereas WC showed a multidirectional association. Conclusions Obesity-related anthropometric indicators were causally associated with increased stool frequency in the overall and central obesity groups. Weight loss could be a potential approach to improve gastrointestinal regularity in individuals with obesity.

Background/Aims: Obesity is associated with several gastrointestinal (GI) disorders and has been identified as a potential risk factor for various GI symptoms. Bowel frequency is an important indicator of bowel function. However, the causal link between obesity and gastrointestinal motility remains uncertain. This study aims to determine the causal effect of overall and central obesity on stool frequency. Methods: Four obesity-related anthropometric indicators–body mass index, body fat percentage, waist circumference (WC), and waist-tohip ratio (WHR)–were investigated. Individual-level baseline information from the UK Biobank was used to explore observational associations between obesity and stool frequency. Additionally, summary-level data from published genome-wide association studies were subjected to two-sample Mendelian randomization (MR) analyses to examine causal associations. Results: For all 4 indicators of obesity, higher levels of obesity were associated with more frequent bowel movements after adjusting for demographic characteristics, lifestyle, and dietary factors. After rigorous screening, 482 body mass index single nucleotide polymorphisms (SNPs), 7 body fat percentage SNPs, 48 WC SNPs, and 287 WHR SNPs were identified as instrument variables for MR analysis. The MR results were generally consistent with observational findings, proving that the associations observed in the overall obesity indicators were causal. For central obesity, the association between WHR and stool frequency remained consistent in both analysis phases, whereas WC showed a multidirectional association. Conclusions Obesity-related anthropometric indicators were causally associated with increased stool frequency in the overall and central obesity groups. Weight loss could be a potential approach to improve gastrointestinal regularity in individuals with obesity.

Objective To explore the behavioral patterns and hippocampal neurogenesis of CHD8+mice,and to provide behavioral and morphological basis for improving autism like behavior and neurogenesis.Methods Genotype of wild type(WT)and CHD8+/-mice was identified.Weight measurement was conducted on both male and female mice of the WT and CHD8+/-strains.Subsequently,a battery of behavioral tests was administered,which included three-chamber test,self-grooming test,nesting test,Y-maze spontaneous alternation test,food burial test,open-field test and light-dark transition test.Afterwards,the mice were administered 2％pentobarbital sodium(2 ml/kg)to induce anesthesia.Their brains were frozen with 4％paraformaldehyde,removed for photography and analysis to identify any alterations in brain size.Western blotting and immunofluorescent labeling were used to detect changes in the process of hippocampus neurogenesis.Results Western blotting analysis demonstrated a decrease in the amounts of chromodomain helicase DNA binding protein 8(CHD8)protein in both male and female mice with CHD8+genotype,as compared to WT mice.There were no notable disparities in body weight between male and female WT and CHD8+mice,as well as in brain size.The three-chamber social behavior test revealed that both male and female CHD8+/-mice had social deficiencies(P＜0.05).During the open field test,there was no significant difference in the total distance moved by male and female WT and CHD8+/-mice.However,the amount of time spent in the central region was considerably lower in CHD8+/-mice compared to the WT mice(P＜0.01).Furthermore,the light-dark transition test revealed that both male and female CHD8+/-mice spent considerably less time investigating the white box compared to the WT mice(P＜0.05).Nevertheless,there were no notable alterations found in self-grooming,nesting,spontaneous alternation of Y-maze,and food burial experiments.In addition,Western blotting result demonstrated a significant drop in doublecortin(DCX)expression(P＜0.001),and immunofluorescent staining revealed a notable reduction in the number of DCX+cells(P＜0.01)in the hippocampus of CHD8+/-mice.Conclusion CHD8+/-mice exhibit social disorders and anxiety-like behaviors,with a decrease in the number of newly generated neurons in the hippocampus and neurogenesis disorders.

Background/Aims: Obesity is associated with several gastrointestinal (GI) disorders and has been identified as a potential risk factor for various GI symptoms. Bowel frequency is an important indicator of bowel function. However, the causal link between obesity and gastrointestinal motility remains uncertain. This study aims to determine the causal effect of overall and central obesity on stool frequency. Methods: Four obesity-related anthropometric indicators–body mass index, body fat percentage, waist circumference (WC), and waist-tohip ratio (WHR)–were investigated. Individual-level baseline information from the UK Biobank was used to explore observational associations between obesity and stool frequency. Additionally, summary-level data from published genome-wide association studies were subjected to two-sample Mendelian randomization (MR) analyses to examine causal associations. Results: For all 4 indicators of obesity, higher levels of obesity were associated with more frequent bowel movements after adjusting for demographic characteristics, lifestyle, and dietary factors. After rigorous screening, 482 body mass index single nucleotide polymorphisms (SNPs), 7 body fat percentage SNPs, 48 WC SNPs, and 287 WHR SNPs were identified as instrument variables for MR analysis. The MR results were generally consistent with observational findings, proving that the associations observed in the overall obesity indicators were causal. For central obesity, the association between WHR and stool frequency remained consistent in both analysis phases, whereas WC showed a multidirectional association. Conclusions Obesity-related anthropometric indicators were causally associated with increased stool frequency in the overall and central obesity groups. Weight loss could be a potential approach to improve gastrointestinal regularity in individuals with obesity.

Objective : To investigate the effects of microRNA-29a(miR-29a) in mediating the regulation of dihydroartemisinin(DHA) on the immune checkpoint molecule B7H3 in lung adenocarcinoma(LUAD). Methods: The expression level and prognostic significance of B7H3 in LUAD were analyzed by public database. Small interfering RNA(siRNA) was used to knock down B7H3 in LUAD cell lines A549 and HCC827, and cell proliferation was detected by CCK-8 method. A549 and HCC827 cells were treated with gradient concentrations of DHA(0, 5, 10, 25, 50, 100 μmol/L) for 48 h, and the half maximal inhibitory concentrate(IC50) was calculated. A549 and HCC827 cells were treated with IC50concentration of DHA for 1, 2 and 3 days, and the cell proliferation was detected by CCK-8 method. A549 and HCC827 cells were transfected with miR-29a inhibitor. After DHA treatment, the expression level of miR-29a was detected by RT-qPCR, and the expression level of B7H3 was detected by Western blot. Results : B7H3 was overexpressed in LUAD and associated with poor prognosis. After knocking down of B7H3, the proliferation ability of A549 and HCC827 cells significantly decreased(allP<0.001). DHA inhibited the proliferation of A549 and HCC827 cells in both dose-and time-dependent manners, with IC50values of 30.16 μmol/L and 7.50 μmol/L, respectively. DHA up-regulated the expression of miR-29a in A549 and HCC827 cells(P<0.001,P<0.01), and down-regulated the expression of B7H3 in both cell lines(P<0.01,P<0.001). After transfection of miR-29a inhibitor into A549 and HCC827 cells, the expression of B7H3 was up-regulated, and the down-regulation of B7H3 by DHA was partially reversed. Conclusion miR-29a mediates the molecular regulation of DHA on B7H3 in LUAD.