1.Additional benefits of pelvic floor proprioceptive training combined with conventional therapy in the treatment of female stress urinary incontinence.
Xiulan ZHANG ; Liping ZHU ; Xiaoling ZENG ; Zhaoxue LIU ; Shuo YANG ; Hong ZHANG ; Wenguang YAN ; Xuhong LI
Journal of Central South University(Medical Sciences) 2025;50(8):1385-1397
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
2.Correlation between serum uric acid, cystatin C, urinary β2-microglobulin and carotid intima-media thickness in patients with diabetic nephropathy and their predictive value in atherosclerosis
Chinese Journal of Postgraduates of Medicine 2025;48(12):1136-1140
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.
3.Study on the brain functional network and structural-functional coupling in children with drug-resistant epilepsy
Xuhong LI ; Jianhui XIAO ; Heng LIU ; Yulun HE ; Haifeng RAN ; Yuxin XIE ; Guiqin CHEN ; Qian′e YU ; Zhen ZENG ; Wenfu LI ; Tijiang ZHANG
Chinese Journal of Radiology 2025;59(2):184-191
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.
4.The role of GPNMB in hypoxia induced epithelial-mesenchymal transition in human chorionic trophoblast cells
Tian TIAN ; Ping CAO ; Xuhong ZHANG ; Xiaohong MA ; Jingrui LI ; Xueqin DING ; Xiaoming YANG
The Journal of Practical Medicine 2025;41(20):3135-3144
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.
5.The role of GPNMB in hypoxia induced epithelial-mesenchymal transition in human chorionic trophoblast cells
Tian TIAN ; Ping CAO ; Xuhong ZHANG ; Xiaohong MA ; Jingrui LI ; Xueqin DING ; Xiaoming YANG
The Journal of Practical Medicine 2025;41(20):3135-3144
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.
6.Correlation between serum uric acid, cystatin C, urinary β2-microglobulin and carotid intima-media thickness in patients with diabetic nephropathy and their predictive value in atherosclerosis
Chinese Journal of Postgraduates of Medicine 2025;48(12):1136-1140
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.
7.Study on the brain functional network and structural-functional coupling in children with drug-resistant epilepsy
Xuhong LI ; Jianhui XIAO ; Heng LIU ; Yulun HE ; Haifeng RAN ; Yuxin XIE ; Guiqin CHEN ; Qian′e YU ; Zhen ZENG ; Wenfu LI ; Tijiang ZHANG
Chinese Journal of Radiology 2025;59(2):184-191
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.
8.Mechanism of Qingfei Huatan Zhuyu Decoction in Treatment of COPD Based on "Lung and Intestinal Co-treatment"
Xuhong WANG ; Jie SHI ; Muying ZHANG ; Jie GAO
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(4):124-133
ObjectiveTo observe the effect of Qingfei Huatan Zhuyu decoction on the lung and intestinal function of rats with chronic obstructive pulmonary diseases (COPD) and explore the deep-seated mechanism of its embodiment of lung and intestinal co-treatment. MethodA total of 60 Wistar rats were randomly divided into six groups, with 10 rats in each group, and the groups were control group, model group, acute syrup group (10 g·kg-1·d-1), and low, medium, and high-dose groups (10, 15, 20 g·kg-1·d-1) of Qingfei Huatan Zhuyu decoction. The COPD rat model was established by lipopolysaccharide tracheal drip combined with the smoke inhalation method, and the acute syrup group and the Qingfei Huatan Zhuyu decoction group were administered by gavage with corresponding dose concentrations respectively, while the rest groups were controlled by saline gavage, and the lung function and blood gas indexes of rats were monitored after the last administration. The histopathological changes in the lung and intestine were observed microscopically. The expression of serum interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and secretory immunoglobulin A (IgA) in colon tissue were measured by enzyme-linked immunosorbent assay (ELISA). The biochemical indexes such as serum diamine oxidase (DAO), D-lactic acid, and malondialdehyde (MDA) were measured. Immunohistochemistry was used to detect the expression of tight junction protein (Occludin) in rat colon tissue. The expression of F4/80 positive alveolar macrophages in rat lung tissue, and the expression of α-actin (α-SMA) and colonic atresia small band protein-1 (ZO-1) were determined by immunofluorescence. The protein expression of p-NF-κB p65, NF-κB p65, p-p38 MAPK, and p-p38 MAPK and the expression of Occludin and ZO-1 in colon tissue were detected in rat lung tissue by Western blot. ResultCompared with the normal group, the model group had pulmonary dysfunction, reduced forced vital capacity (FVC), arterial partial oxygen pressure (PaO2), arterial oxygen saturation (SaO2), and dynamic lung compliance (Cdyn) (P<0.01), and the pathological changes in the lung and intestine were obvious. The expressions of IL-6, TNF-α, DAO, D-lactic acid, and MDA in serum were increased (P<0.05,P<0.01), and the protein expression ratio of p-NF-κB p65/NF-κB p65 and p-p38 MAPK/p38 MAPK in lung tissue was increased. The expression of F4/80 positive macrophages in lung tissue was enhanced. The expression of IgA, Occludin, and ZO-1 in colon tissue decreased (P<0.05,P<0.01). Compared with the model group, the pulmonary function of the rats in the acute syrup group and groups of Qingfei Huatan Zhuyu decoction was significantly improved, and the FVC, PaO2, SaO2, and Cdyn were increased (P<0.05, P<0.01). The pathological changes in the lung and intestine were significant. The expressions of IL-6, TNF-α, DAO, D-lactic acid, and MDA in serum were decreased (P<0.05,P<0.01), and the expressions of F4/80 positive macrophages in lung tissue were decreased (P<0.01). The protein expression ratio of p-NF-κB p65/NF-κB p65 and p-p38 MAPK/p38 MAPK in lung tissue decreased (P<0.01), and the expression of IgA, Occludin, and ZO-1 in colon tissue increased (P<0.01). ConclusionQingfei Huatan Zhuyu decoction can effectively reduce the symptoms of COPD rats, and its mechanism of action is related to inhibiting the inflammatory response of lung tissue and improving the barrier function of the intestinal mucosa.
9.Preparation of decellularized bone graft material with supercritical carbon dioxide extraction technique.
Feng HAO ; Kaifeng PAN ; Liuyun HUANG ; Xuhong CHEN ; Haikun WEI ; Xianhua CHEN ; Jianfeng ZHANG
Journal of Zhejiang University. Medical sciences 2024;53(6):772-778
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*
10.Arrhythmias and electrocardiographic characteristics in cancer patients treated with immune checkpoint inhibitors
Xuhong GENG ; Nan ZHANG ; Wenhua SONG ; Siyao CHENG ; Yi ZHENG ; Xiaotong MA ; Li WANG ; Xuan LI ; Tong LIU
Chinese Journal of Cardiology 2024;52(6):690-697
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.

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