OBJECTIVES: Stress urinary incontinence (SUI) is a common condition among women that severely impairs quality of life. Pelvic floor proprioceptive training (PFPT) has attracted increasing attention for its potential to enhance pelvic floor muscle function and alleviate SUI symptoms. This study aims to observe and compare the clinical efficacy of PFPT combined with electroacupuncture, electrical stimulation, and biofeedback therapy versus conventional therapy consisting of electroacupuncture, electrical stimulation, and biofeedback alone in women with SUI, and to explore the role of PFPT in improving symptom and functional outcomes. METHODS: In this randomized controlled trial, 72 women with mild to moderate SUI were recruited from the Department of Rehabilitation Medicine at Third Xiangya Hospital, Central South University, between December 2021 and October 2023. Participants were randomly assigned to an experimental group (n=36) or a control group (n=36). Both groups received health education. The control group underwent electroacupuncture combined with electrical stimulation and biofeedback therapy, while the experimental group additionally received PFPT 3 times per week for 4 weeks. The primary outcome was assessed using the International Consultation on Incontinence Questionnaire-Short Form (ICIQ-SF). Secondary outcomes included pelvic floor muscle strength, bladder neck mobility, and balance ability. The ICIQ-SF was reassessed at 1, 3, 6, and 12 months post-treatment. RESULTS: Both groups showed statistically significant improvements in all parameters after treatment (all P<0.05). However, there were no statistically significant differences between groups in most measures (all P>0.05). The experimental group demonstrated longer single-leg stance duration with eyes closed than the control group (left leg: P=0.026; right leg: P=0.006), with a significant increase from baseline (P<0.001). At 6 months post-treatment, the cure rate in the experimental group was significantly higher than that in the control group (P=0.037). CONCLUSIONS Conventional therapy effectively improves SUI symptoms, but adding PFPT provides notable additional benefits, including enhanced balance ability and sustained mid-term cure rates. These findings suggest that PFPT is a valuable adjunct to standard SUI management strategies.
Humans ; Female ; Urinary Incontinence, Stress/physiopathology* ; Pelvic Floor/physiopathology* ; Middle Aged ; Biofeedback, Psychology ; Adult ; Exercise Therapy/methods* ; Proprioception ; Electroacupuncture/methods* ; Quality of Life ; Electric Stimulation Therapy/methods* ; Treatment Outcome ; Combined Modality Therapy

Objective:To investigate the changes in brain functional network and structural-functional network coupling in children with drug-resistant epilepsy (DRE), and to analyze their correlation with cognitive function, disease duration, and age of onset.Methods:This study was a cross-sectional study. Clinical and imaging data of 19 children with DRE who received consultation and treatment at the Affiliated Hospital of Zunyi Medical University from August 2021 to August 2023 (DRE group) were prospectively included. Another 27 age-and sex-matched healthy children were collected as the healthy control group. All subjects had 3D-T 1WI, T 2 fluid-attenuated inversion recovery, diffusion tensor imaging (DTI), resting-state functional magnetic resonance imaging (rs-fMRI) scans and Wechsler Intelligence Scale assessments. Independent sample t-test and Mann-Whitney U test were used to analyze the global and local topological attributes, as well as the structural-functional coupling (SFC) values at the whole brain and modular levels in two groups. Correlations between abnormal resting state brain functional network indicators and the Wechsler Intelligence Scale score [verbal comprehension index (VCI), perceptual reasoning index (PRI), working memory index (WMI), processing speed index (PSI), full scale intelligence quotient (FSIQ)], disease duration and age of onset was evaluated using a Spearman or Pearson correlation analysis. Results:Compared to the healthy control group, DRE group exhibited decreased VCI, PRI, WMI, PSI, FSIQ and the differences were all statistically significant (all P<0.05). Both brain functional networks had small world attributes. There was a statistically significant difference in the area under the curve of sparsity of degree centrality (DC) in the left pallidum between the DRE group and healthy control group (2.998±0.942, 4.992±1.945, t=-4.07, FDR corrected P<0.05). Compared with the control group, the DRE group had decreased SFC within the limbic network (LN) ( P<0.05), increased SFC within the sensorimotor (SMN) ( P<0.05), decreased SFC between the default mode network-LN ( P<0.05), and increased SFC between the SMN-attentional network (AN) ( P<0.05). There was no statistically significant difference in SFC at the whole brain level between the two groups. Correlation analysis indicated that DC in left pallidum in DRE group negatively correlated with the PSI ( r=-0.537, P=0.018), and SFC between the SMN and AN demonstrated a negative correlation with age of onset ( r=-0.537, P=0.018). Conclusion:The altered DC in left pallidum may be related to cognitive impairment in children with DRE, providing biomarker information for the study of neural mechanisms in children with DRE.

Objective To investigate the role of Glycoprotein non-metastatic melanoma protein B(GPNMB)in hypoxia-induced epithelial-mesenchymal transition(EMT)in human chorionic trophoblast HTR-8/SVneo cells.Methods HTR-8/SVneo cells were cultured in vitro to investigate the effect of hypoxia on GPNMB expression.The cells were transfected with either a GPNMB overexpression plasmid(pcDNA3.1-GPNMB),small interfering RNA targeting GPNMB(si-GPNMB-1/2),or their respective negative controls(pcDNA3.1-NC or si-NC),and were also treated with the autophagy agonist rapamycin(Rap).The experimental groups were categorized as follows:Normoxia,Hypoxia,Normoxia/Hypoxia+si-NC or si-GPNMB,Normoxia/Hypoxia+pcDNA3.1-NC or pcDNA3.1-GPNMB,Normoxia/Hypoxia+Rap,and Hypoxia+Rap+pcDNA3.1-NC or pcDNA3.1-GPNMB.GPNMB expression levels were evaluated using qRT-PCR,Western blotting,and immunofluorescence staining.The expression of autophagy-related proteins(LC3B Ⅱ/Ⅰ,p62)and epithelial-mesenchymal transition(EMT)markers(E-cadherin,N-cadherin)was analyzed by Western blotting.Cell migration and invasion capacities were assessed using wound healing and Transwell assays.Results Compared with the Normoxia group,the mRNA and protein levels of GPNMB were downregulated in the Hypoxia group.Additionally,the protein levels of p62 and N-cadherin were reduced,while LC3B Ⅱ/Ⅰ and E-cadherin expression levels were increased(P<0.05).Compared with the Hypoxia+si-NC group,the Hypoxia+si-GPNMB-2 group showed significantly decreased protein levels of p62 and N-cadherin,along with elevated levels of LC3B Ⅱ/Ⅰ and E-cadherin(P<0.05).Compared with the Hypoxia+pcDNA3.1-NC group,the Hypoxia+pcDNA3.1-GPNMB group exhibited opposite trends.Notably,compared with the Hypoxia group,the Hypoxia+Rap group showed increased LC3B Ⅱ/Ⅰ and E-cadherin levels,accompanied by reduced p62 and N-cadherin levels(P<0.05).However,compared with the Hypoxia+pcDNA3.1-GPNMB group,the Hypoxia+Rap+pcDNA3.1-GPNMB group attenuated the promoting effect of GPNMB overexpression on EMT in HTR-8/SVneo cells,as evidenced by decreased p62 and N-cadherin protein expression levels and increased LC3BⅡ/Ⅰ and E-cadherin protein expression levels(P<0.05).Conclusion In hypoxia-induced HTR-8/SVneo cells,GPNMB inhibits autophagy,promotes the epithelial-mesenchymal transition,and enhances cell migration and invasion.

Objective:To analyze the correlation between serum uric acid (UA), cystatin C (CysC), urinary β2-microglobulin (β2-MG) and carotid intima-media thickness (IMT) in patients with diabetic nephropathy (DN) and their predictive value in atherosclerosis (AS).Methods:The clinical data of 250 patients with type 2 diabetes mellitus (T2DM) diagnosed and treated in the Seventh People's Hospital Affiliated to Shanghai University of Traditional Chinese Medicine from November 2020 to November 2023 were retrospectively analyzed. They were divided into T2DM group (125 cases) and DN group (125 cases) according to whether they had concurrent DN. Another 125 healthy subjects in the same period were selected as the healthy control group. The levels of UA, CysC, urinary β2-MG and IMT were compared among the three groups. The levels of UA, CysC and urinary β2-MG in different IMT groups (IMT<1.0 mm group, IMT 1.0 - 1.5 mm group, IMT>1.5 mm group) in DN patients were compared, and the correlation between UA, CysC, urinary β2-MG and IMT was analyzed by Pearson test. Receiver operating characteristic (ROC) curve was used to analyze the predictive efficacy of UA, CysC and urinary β2-MG in patients with DN.Results:The levels of UA, CysC, urinary β2-MG and IMT in the DN group were higher than those in the T2DM group and the healthy control group : (516.55 ± 90.62) μmol/L vs.(320.16 ± 98.62), (204.82 ± 48.64) μmol/L; (2.06 ± 0.99) mg/L vs. (0.82 ± 0.24), (0.66 ± 0.10) mg/L; (2.95 ± 1.02) mg/L vs. (1.16 ± 0.33), (0.82 ± 0.16) mg/L; (0.26 ± 0.08) cm vs. (0.16 ± 0.04), (0.07 ± 0.01) cm, and the levels of UA, CysC, urinary β2-MG in the T2DM group were higher than those in the healthy control group, there were statistical differences ( P<0.05). The levels of serum UA, CysC and urinary β2-MG in the IMT<1.0 mm group were lower than those in the IMT 1.0 - 1.5 mm group and IMT>1.5 mm group: (468.37 ± 61.85) μmol/L vs. (524.16 ± 82.06), (551.92 ± 94.55) μmol/L; (1.82 ± 0.16) mg/L vs. (2.04 ± 0.33), (2.45 ± 0.62) mg/L; (2.57 ± 0.11) mg/L vs. (2.98 ± 0.18), (3.34 ± 0.26) mg/L, and serum UA, CysC and urinary β2-MG in the IMT 1.0 - 1.5 mm group were lower than those in the IMT>1.5 mm group, there were statistical differences ( P<0.05). The results of Pearson test showed that UA, CysC, urinary β2-MG were positively correlated with IMT ( r = 0.369, 0.406, 0.382, P<0.05). ROC curve analysis results showed that the combined detection of serum UA, CysC and urinary β2-MG predicted the area under the curve (AUC) of AS in DN patients was 0.904. Conclusions:The abnormal increase of serum UA, CysC and urine β 2-MG are closely related to the occurrence of AS in DN patients. Combined detection has high predictive power for AS and can serve as a potential indicator for clinical prediction of AS in DN patients.

Objective To investigate the role of Glycoprotein non-metastatic melanoma protein B(GPNMB)in hypoxia-induced epithelial-mesenchymal transition(EMT)in human chorionic trophoblast HTR-8/SVneo cells.Methods HTR-8/SVneo cells were cultured in vitro to investigate the effect of hypoxia on GPNMB expression.The cells were transfected with either a GPNMB overexpression plasmid(pcDNA3.1-GPNMB),small interfering RNA targeting GPNMB(si-GPNMB-1/2),or their respective negative controls(pcDNA3.1-NC or si-NC),and were also treated with the autophagy agonist rapamycin(Rap).The experimental groups were categorized as follows:Normoxia,Hypoxia,Normoxia/Hypoxia+si-NC or si-GPNMB,Normoxia/Hypoxia+pcDNA3.1-NC or pcDNA3.1-GPNMB,Normoxia/Hypoxia+Rap,and Hypoxia+Rap+pcDNA3.1-NC or pcDNA3.1-GPNMB.GPNMB expression levels were evaluated using qRT-PCR,Western blotting,and immunofluorescence staining.The expression of autophagy-related proteins(LC3B Ⅱ/Ⅰ,p62)and epithelial-mesenchymal transition(EMT)markers(E-cadherin,N-cadherin)was analyzed by Western blotting.Cell migration and invasion capacities were assessed using wound healing and Transwell assays.Results Compared with the Normoxia group,the mRNA and protein levels of GPNMB were downregulated in the Hypoxia group.Additionally,the protein levels of p62 and N-cadherin were reduced,while LC3B Ⅱ/Ⅰ and E-cadherin expression levels were increased(P<0.05).Compared with the Hypoxia+si-NC group,the Hypoxia+si-GPNMB-2 group showed significantly decreased protein levels of p62 and N-cadherin,along with elevated levels of LC3B Ⅱ/Ⅰ and E-cadherin(P<0.05).Compared with the Hypoxia+pcDNA3.1-NC group,the Hypoxia+pcDNA3.1-GPNMB group exhibited opposite trends.Notably,compared with the Hypoxia group,the Hypoxia+Rap group showed increased LC3B Ⅱ/Ⅰ and E-cadherin levels,accompanied by reduced p62 and N-cadherin levels(P<0.05).However,compared with the Hypoxia+pcDNA3.1-GPNMB group,the Hypoxia+Rap+pcDNA3.1-GPNMB group attenuated the promoting effect of GPNMB overexpression on EMT in HTR-8/SVneo cells,as evidenced by decreased p62 and N-cadherin protein expression levels and increased LC3BⅡ/Ⅰ and E-cadherin protein expression levels(P<0.05).Conclusion In hypoxia-induced HTR-8/SVneo cells,GPNMB inhibits autophagy,promotes the epithelial-mesenchymal transition,and enhances cell migration and invasion.

Objective:To analyze the correlation between serum uric acid (UA), cystatin C (CysC), urinary β2-microglobulin (β2-MG) and carotid intima-media thickness (IMT) in patients with diabetic nephropathy (DN) and their predictive value in atherosclerosis (AS).Methods:The clinical data of 250 patients with type 2 diabetes mellitus (T2DM) diagnosed and treated in the Seventh People's Hospital Affiliated to Shanghai University of Traditional Chinese Medicine from November 2020 to November 2023 were retrospectively analyzed. They were divided into T2DM group (125 cases) and DN group (125 cases) according to whether they had concurrent DN. Another 125 healthy subjects in the same period were selected as the healthy control group. The levels of UA, CysC, urinary β2-MG and IMT were compared among the three groups. The levels of UA, CysC and urinary β2-MG in different IMT groups (IMT<1.0 mm group, IMT 1.0 - 1.5 mm group, IMT>1.5 mm group) in DN patients were compared, and the correlation between UA, CysC, urinary β2-MG and IMT was analyzed by Pearson test. Receiver operating characteristic (ROC) curve was used to analyze the predictive efficacy of UA, CysC and urinary β2-MG in patients with DN.Results:The levels of UA, CysC, urinary β2-MG and IMT in the DN group were higher than those in the T2DM group and the healthy control group : (516.55 ± 90.62) μmol/L vs.(320.16 ± 98.62), (204.82 ± 48.64) μmol/L; (2.06 ± 0.99) mg/L vs. (0.82 ± 0.24), (0.66 ± 0.10) mg/L; (2.95 ± 1.02) mg/L vs. (1.16 ± 0.33), (0.82 ± 0.16) mg/L; (0.26 ± 0.08) cm vs. (0.16 ± 0.04), (0.07 ± 0.01) cm, and the levels of UA, CysC, urinary β2-MG in the T2DM group were higher than those in the healthy control group, there were statistical differences ( P<0.05). The levels of serum UA, CysC and urinary β2-MG in the IMT<1.0 mm group were lower than those in the IMT 1.0 - 1.5 mm group and IMT>1.5 mm group: (468.37 ± 61.85) μmol/L vs. (524.16 ± 82.06), (551.92 ± 94.55) μmol/L; (1.82 ± 0.16) mg/L vs. (2.04 ± 0.33), (2.45 ± 0.62) mg/L; (2.57 ± 0.11) mg/L vs. (2.98 ± 0.18), (3.34 ± 0.26) mg/L, and serum UA, CysC and urinary β2-MG in the IMT 1.0 - 1.5 mm group were lower than those in the IMT>1.5 mm group, there were statistical differences ( P<0.05). The results of Pearson test showed that UA, CysC, urinary β2-MG were positively correlated with IMT ( r = 0.369, 0.406, 0.382, P<0.05). ROC curve analysis results showed that the combined detection of serum UA, CysC and urinary β2-MG predicted the area under the curve (AUC) of AS in DN patients was 0.904. Conclusions:The abnormal increase of serum UA, CysC and urine β 2-MG are closely related to the occurrence of AS in DN patients. Combined detection has high predictive power for AS and can serve as a potential indicator for clinical prediction of AS in DN patients.

Objective:To investigate the changes in brain functional network and structural-functional network coupling in children with drug-resistant epilepsy (DRE), and to analyze their correlation with cognitive function, disease duration, and age of onset.Methods:This study was a cross-sectional study. Clinical and imaging data of 19 children with DRE who received consultation and treatment at the Affiliated Hospital of Zunyi Medical University from August 2021 to August 2023 (DRE group) were prospectively included. Another 27 age-and sex-matched healthy children were collected as the healthy control group. All subjects had 3D-T 1WI, T 2 fluid-attenuated inversion recovery, diffusion tensor imaging (DTI), resting-state functional magnetic resonance imaging (rs-fMRI) scans and Wechsler Intelligence Scale assessments. Independent sample t-test and Mann-Whitney U test were used to analyze the global and local topological attributes, as well as the structural-functional coupling (SFC) values at the whole brain and modular levels in two groups. Correlations between abnormal resting state brain functional network indicators and the Wechsler Intelligence Scale score [verbal comprehension index (VCI), perceptual reasoning index (PRI), working memory index (WMI), processing speed index (PSI), full scale intelligence quotient (FSIQ)], disease duration and age of onset was evaluated using a Spearman or Pearson correlation analysis. Results:Compared to the healthy control group, DRE group exhibited decreased VCI, PRI, WMI, PSI, FSIQ and the differences were all statistically significant (all P<0.05). Both brain functional networks had small world attributes. There was a statistically significant difference in the area under the curve of sparsity of degree centrality (DC) in the left pallidum between the DRE group and healthy control group (2.998±0.942, 4.992±1.945, t=-4.07, FDR corrected P<0.05). Compared with the control group, the DRE group had decreased SFC within the limbic network (LN) ( P<0.05), increased SFC within the sensorimotor (SMN) ( P<0.05), decreased SFC between the default mode network-LN ( P<0.05), and increased SFC between the SMN-attentional network (AN) ( P<0.05). There was no statistically significant difference in SFC at the whole brain level between the two groups. Correlation analysis indicated that DC in left pallidum in DRE group negatively correlated with the PSI ( r=-0.537, P=0.018), and SFC between the SMN and AN demonstrated a negative correlation with age of onset ( r=-0.537, P=0.018). Conclusion:The altered DC in left pallidum may be related to cognitive impairment in children with DRE, providing biomarker information for the study of neural mechanisms in children with DRE.

OBJECTIVES: To evaluate the immunogenicity and osteogenic ability of animal-derived bone graft material decellularized with supercritical carbon dioxide. METHODS: Porcine femurs were randomly divided into two groups after preliminary treatment, and decellularized with conventional method (control group) or supercritical carbon dioxide (experimental group). Allogenic demineralized bone matrix was used as positive control. Clearance rate of galactose-α-1, 3-galactose (α-Gal) antigen was determined by enzyme-linked immunosorbent assay and residual DNA was detected by a fluorescence method. Nine SPF-grade male athymic nude mice of 6 weeks old were randomly divided into experimental, control and positive control groups. Samples were implanted over biceps femoris muscle of athymic nude mice. The explants were collected 4 weeks post implantation. Hematoxylin and eosin (HE) staining and immunohistochemistry were applied to determine the osteogenic ability and bone tissue-associated protein expressions of the implants. RESULTS: The clearance rates of α-Gal antigen in the experimental group and the control group were (99.09±0.26)% and (30.18±2.02)%, respectively (t=58.67, P<0.01). The residual DNA of the experimental, control and positive control groups were (13.49±0.07), (15.20±0.21) and (14.70±0.17) ng/mg. The residual DNA in the experimental group was significantly lower than that in the control group (t=－13.41, P<0.01) and positive control group (t=－11.30, P<0.01). HE staining results showed that multiple bone formation centers with active osteogenesis and rich bone marrow were observed in experimental group 4 weeks after implantation, but only a small number of bone formation centers were observed in the control and positive control groups, with no obvious osteoblasts present. Immunohistochemistry results indicated that the expressions of alkaline phosphatase, Runt-related transcription factor 2, collagen typeⅠand osteocalcin in the experimental group showed an increasing trend compared with those in the control and positive control groups. CONCLUSIONS Compared with clinically used allogenic demineralized bone matrix and bone graft material decellularized with conventional method, bone graft material decellularized with supercritical carbon dioxide exhibits lower immunogenicity and better osteogenic ability.
Animals ; Mice ; Swine ; Male ; Bone Transplantation/methods* ; Mice, Nude ; Carbon Dioxide ; Osteogenesis/drug effects* ; Femur ; Bone Substitutes ; Tissue Engineering/methods*

OBJECTIVES: Pelvic organ prolapse (POP) is a common condition in postmenopausal women, with an increasing prevalence due to aging. Some women experience POP recurrence after surgical treatment, significantly affecting their physical and mental health. The uterosacral ligament is a critical pelvic support structure. This study aims to investigate the molecular pathological changes in the uterosacral ligament of postmenopausal women with recurrent POP using transcriptomic analysis. METHODS: Transcriptomic data of uterosacral ligament tissues were obtained from the public dataset GSE28660, which includes samples from 4 postmenopausal women with recurrent POP, 4 with primary POP, and 4 without POP. Differentially expressed genes (DEGs) were identified between recurrent POP and both primary and non-POP groups. Further analysis included intersection analysis of DEGs, gene ontology enrichment, protein-protein interaction (PPI) network construction, gene set enrichment analysis (GSEA), single-sample GSEA, and xCell immune cell infiltration analysis to explore molecular pathological changes in recurrent POP. Additionally, histological and molecular differences in the uterosacral ligament were compared between simulated vaginal delivery (SVD) rat models with and without ovariectomy. RESULTS: Compared with primary POP and non-POP groups, recurrent POP exhibited activation of adipogenesis and inflammation-related pathways, while pathways related to muscle proliferation and contraction were downregulated in the uterosacral ligament. Nine key DEGs (ADIPOQ, FABP4, IL-6, LIPE, LPL, PCK1, PLIN1, PPARG, and CD36) were identified, with most enriched in the peroxisome proliferator-activated receptor (PPAR) signaling pathway. These genes were significantly correlated with lipid accumulation, monocyte infiltration, and neutrophil infiltration in the uterosacral ligament. Urodynamic testing revealed that the bladder leak point pressure was significantly higher in ovariectomized SVD rats, both of which had higher values than the sham group. Masson staining showed pronounced adipogenesis in the uterosacral ligament of ovariectomized SVD rats, along with reduced collagen and muscle fibers compared to the sham and non-ovariectomized SVD groups. Furthermore, real-time RT-PCR confirmed significantly elevated expression of key DEGs, including ADIPOQ, IL-6, PCK1, and PLIN1, in the uterosacral ligaments of ovariectomized SVD rats. CONCLUSIONS Adipogenesis and inflammation in the uterosacral ligament may contribute to its reduced supportive function, potentially leading to recurrence POP in postmenopausal women.
Female ; Humans ; Ligaments/pathology* ; Pelvic Organ Prolapse/metabolism* ; Postmenopause ; Animals ; Rats ; Adipogenesis/genetics* ; Recurrence ; Gene Expression Profiling ; Transcriptome ; Middle Aged ; Ovariectomy ; Protein Interaction Maps ; Aged ; Rats, Sprague-Dawley ; Uterus

OBJECTIVES: Pelvic floor sensory training is commonly used in clinical practice for the treatment of stress urinary incontinence (SUI); however, there is a lack of comparative studies evaluating pelvic floor sensation between women with SUI and healthy controls. Additionally, normative data for two-point discrimination thresholds in the female pelvic floor region remain scarce. This study aims to compare the results of 4 sensory tests in the pelvic floor region between women with mild SUI and healthy women, in order to provide reference values for two-point discrimination thresholds in this area. METHODS: From April 1 to October 30, 2023, 108 healthy women [(32.5±3.6) years] and 90 women with mild SUI [(32.9±3.3) years] were recruited from the Third Xiangya Hospital, Central South University. Participants underwent 4 sensory tests in the pelvic floor region: Two-dot discrimination, weight perception, shape recognition, and 9-grid localization. The results were compared between the 2 groups. RESULTS: Compared with healthy women, those with mild SUI had lower sensitivity and higher thresholds in 2-dot discrimination tests in the pelvic floor region (all P<0.001). No significant differences were found between groups in weight perception, shape recognition, or grid localization tests (P>0.05). CONCLUSIONS Women with mild stress urinary incontinence have impaired two-point discrimination ability in the pelvic floor region.
Humans ; Female ; Urinary Incontinence, Stress/physiopathology* ; Pelvic Floor/physiopathology* ; Adult ; Sensory Thresholds/physiology*