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 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 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.

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 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.

With the extensive application of uranium in military, industrial and civil fields, the possibility of human exposure to uranium has become increasingly likely. When uranium is accidentally released into the environment, it can enter the human body by various pathways and accumulate in the kidneys, leading to proximal tubule epithelial cell damage or even death, and in severe cases, nephrotoxicity. Uranium exerts both chemical and radiological toxicity, with its kidney-damaging effects primarily attributed to chemical toxicity. Low-level uranium exposure causes mild kidney damage, while prolonged or high-level exposure alters kidney structure and biomarker level of uranium-induced nephrotoxicity (such as creatinine, urea nitrogen and kidney injury molecule-1, etc.). Uranium exposure also induces DNA damage and mutations, kidney inflammation, and renal cell autophagy. Current research on uranium nephrotoxicity primarily focuses on uranium-induced mitochondrial dysfunction, which leads to oxidative stress and apoptosis (mainly by mitochondrial and endoplasmic reticulum pathway), ultimately causing renal tissue damage. However, the molecular mechanisms underlying uranium-induced kidney toxicity remain incomplete. Future research on mechanism of uranium-induced cell damage, especially metabolism, intracellular distribution, and additional mechanisms, remains a long-term and challenging endeavor.

BACKGROUND:Increased homocysteine level induces apoptosis of human umbilical vein endothelial cells,but the mechanism remains unclear. OBJECTIVE:To investigate the role of hsa-circ-0001360 in human umbilical vein endothelial cell apoptosis induced by homocysteine. METHODS:In vitro cultured human umbilical vein endothelial cells were divided into control group,homocysteine group,interference control group,interference control + homocysteine group,hsa-circ-0001360 interference group,hsa-circ-0001360 + homocysteine interference group,overexpression control group,overexpression control + homocysteine group,hsa-circ-0001360 overexpression group and hsa-circ-0001360 + homocysteine overexpression group.All groups were treated with 100 μmol/L homocysteine.After 72 hours of intervention,the expressions of apoptosis-related proteins Bax,Bcl-2,and Caspase-3 were detected by western blot assay.The apoptotic rate was detected by flow cytometry.Quantitative real-time PCR was used to detect the expression of hsa-circ-0001360. RESULTS AND CONCLUSION:(1)Compared with the control group,the expression of Caspase-3 and Bax was significantly increased(P<0.01),and the expression of Bcl-2 was significantly decreased(P<0.01),and the apoptotic rate was significantly increased(P<0.01)in the homocysteine group.(2)Compared with control group,the expression of hsa-circ-0001360 was significantly increased in the homocysteine group(P<0.01).(3)The expression of hsa-circ-0001360 was significantly higher in the cytoplasm than that in the nucleus(P<0.01).(4)Compared with the interference control C group and interference control + homocysteine group,the expressions of Caspase-3 and Bax were significantly decreased(P<0.01),while the expression of Bcl-2 was significantly increased(P<0.01);the apoptotic rate was significantly decreased(P<0.01)in sh-hsa-circ-0001360 interference group and sh-hsa-circ-0001360 + homocysteine interference group.(5)Compared with overexpression control group and overexpression control + homocysteine group,the expressions of Caspase-3 and Bax were significantly increased(P<0.01),while the expression of Bcl-2 was significantly decreased(P<0.01);the apoptotic rate was significantly increased(P<0.01)in the hsa-circ-0001360 overexpression group and the hsa-circ-0001360 + homocysteine overexpression group.(6)In conclusion,hsa-circ-0001360 can promote the apoptosis of human umbilical vein endothelial cells induced by homocysteine.

Objective:To evaluate the incidence of arrhythmias and electrocardiographic (ECG) characteristics in cancer patients treated with immune checkpoint inhibitors (ICIs).Methods:This was a cohort study conducted in the Fourth Hospital of Hebei Medical University. Cancer patients initiating ICIs treatments from November 2020 to September 2022 were included in this study. Baseline 12-leads ECG before ICIs initiation and post-treatment ECG were analyzed. An abnormal ECG was defined as the presence of any of the following changes: sinus arrhythmias, atrial fibrillation, atrial flutter, paroxysmal supraventricular tachycardia, ventricular tachycardia, premature contractions, conduction disorder, and ST-T changes.Results:A total of 87 patients were enrolled, aged 63 (57, 68) years, with 66 (75.9%) males. And 44.8% (39/87) of patients presented with at least one confirmed cardiovascular disease or cardiovascular risk factor at baseline. The incidence of abnormal ECG increased from 31.0% (27/87) at baseline to 65.5% (57/87) after receiving (5.0±2.7) cycles of ICIs treatment ( P<0.001). The incidence of sinus arrhythmias was significantly increased after ICIs treatment (23.0% (20/87) vs. 9.2% (8/87), P=0.023), of which only the incidence of sinus tachycardia was significantly increased (11.5% (10/87) vs. 2.3% (2/87), P=0.039). There was also a significantly increased incidence of ST-T changes after ICIs treatment (31.0% (27/87) vs. 17.2% (15/87), P=0.012), which mainly attributed to the T wave changes (29.9% (26/87) vs. 13.8% (12/87), P=0.001). The incidence of premature contractions was also significantly increased after ICIs treatment (9.2% (8/87) vs. 0, P=0.008). Additionally, compared with baseline, the P wave axis was significantly increased after ICIs treatment ((56.94±21.01)° vs. (52.00±22.69)°, P=0.043). After ICIs treatment, the heart rate was significantly increased ((79.07±15.37) beats/min vs. (75.64±13.37) beats/min, P=0.029). Sokolow-Lyon index ((2.21±0.81)mV vs. (2.33±0.75)mV, P=0.138), QTc interval ((431.44±36.04)ms vs. (428.00±30.05)ms, P=0.415) all showed signs of change after treatment, but did not reach the traditional significant level. Conclusions:The incidence of abnormal ECG is significantly increased after ICIs treatment, especially for sinus tachycardia, premature contractions and T wave changes; the P wave axis and heart rate is also significantly increased after treatment. It is important to perform regular ECG monitoring in patients receiving ICIs treatment.