1.A preliminary study of mechanosensitive channels Piezo 1 and Piezo 2 promoting neurogenic bladder fibrosis in young rats
Lei LYU ; Yanping ZHANG ; Qi LI ; Junkui WANG ; Shuai YANG ; Zhaokai ZHOU ; Shuai LI ; Yibo WEN ; Yakai LIU ; Guowei SI ; Xingchen LIU ; Jianguo WEN
Journal of Modern Urology 2025;30(4):343-349
Objective: To explore the changes of mechanosensitive channels Piezos (Piezo 1 and Piezo 2) in neurogenic bladder (NB) of young rats and their effects,so as to provide reference for clinical search of new therapeutic targets. Methods: A total of 30 female young SD rats were divided into 5 groups based on random number table method:sham operation group (sham),2-week nerve transection group (NB-2W),6-week nerve transection group (NB-6W),2-week nerve transection + Piezos inhibitor group (NB-P-2W) and 6-week nerve transection + Piezos inhibitor group (NB-P-6W),with 6 rats in each group.The NB models were constructed by transecting the L6 and S1 spinal nerves of young rats.The NB-2W and NB-6W groups were not intervened after modeling,while the NB-P-2W and NB-P-6W groups were intraperitoneally injected with Piezos inhibitor GsMTx4 (10 mg/kg) every 2 days after modeling.Bladder cystometry and ultrasound were performed after 2 and 6 weeks of transection.The expressions of Piezos and fibrosis-related indexes (Collagen Ⅰ and α-smooth muscle actin) were detected in bladder tissues. Results: The results of bladder cystometry showed that the basal bladder pressure in NB-2W group was significantly increased,while it was slightly decreased but was still higher in NB-6W group than in the sham group (P<0.05).Basal bladder pressure was lower in NB-P-2W group than in NB-2W group,but was higher than that in the sham group; basal bladder pressure was lower in NB-P-6W group than in NB-6W group,but higher than that in the sham group (P<0.05).Compared with the sham group,the NB-2W and NB-6W groups had firstly increased and then decreased maximum cystometric capacity (MCC) (P<0.05).Compared with NB-2W group,NB-P-2W group had lower bladder leakage point pressure (BLPP),but higher MCC and bladder compliance (BC) (P<0.05).Compared with NB-6W group,NB-P-6W group had significantly lower BLPP but higher MCC and BC (P<0.05).HE and MASSON staining and ultrasound results showed that,with the extension of nerve transection time,bladder fibrosis gradually worsened,the bladder wall became rough and thickened,calculi were visible inside,and hydronephrosis gradually appeared; the degree of fibrosis in NB-P-2W and NB-P-6W groups was less than that in NB-2W and NB-6W groups,and no hydronephrosis was observed in the upper urinary tract.In addition,Western blotting and immunohistochemical results showed that NB-2W and NB-6W groups had significantly higher relative expression levels of Piezos,Collagen Ⅰ and α-SMA than the sham group (P<0.01),while NB-P-2W and NB-P-6W groups had lower relative expression levels of Piezos,Collagen Ⅰ and α-SMA than NB-2W and NB-6W groups (P<0.01). Conclusion: The increased expressions of mechanosensitive channels Piezos in NB young rats may be involved in the progression of bladder fibrosis,but its mechanism needs further study.
2.Proteomics and Phosphoproteomics Analysis of Effect of Retinoic Acid-Induced Protein 16 Knockout on Human Colon Cancer Cells
Yibo CHEN ; Gen MIAO ; Wen WANG ; Cuiling DING ; Zhongtian QI
Cancer Research on Prevention and Treatment 2024;51(10):820-830
Objective To analyze the differences in the expressions of the total and phosphorylated proteins in human colon cancer HCT116 cells after the knockout(KO)of retinoic acid-induced protein 16(RAI16)and explore the possible mechanism and related signaling pathways affecting its protein function in HCT116 cells.Methods HCT116 KO and WT cell proteins were collected and extracted,and the protein extraction efficiency was detected via a sodium dodecyl sulfate-polyacrylamide gel electrophoresis(SDS-PAGE)experiment.After protein digestion,the peptides were labeled with TMT and analyzed via mass spectrometry.We used bioinformatics methods to analyze the identified differential proteins and differentially phosphory-lated proteins by using GO,KEGG,and STRING databases.Results The results of SDS-PAGE showed no evident protein degradation.In addition,some key bands were significantly different between the experi-mental and control groups.A total of 147 up-regulated and 230 down-regulated differential proteins were screened in accordance with the conditions of Foldchange≥1.5 or Foldchange≤1/1.5 and P<0.05.Meanwhile,106 up-regulated and 217 down-regulated phosphorylation sites were screened.GO enrichment analysis revealed that the differential proteins were mainly enriched in the composition of nucleoplasm,nucleus and cytoplasm,RNA binding,cadherin and chromatin,DNA repair,RNA splicing,and positive regulation of DNA as template transcription.The results of KEGG enrichment indicated that the differential proteins were mainly enriched in nucleocytoplasmic transport,spliceosomes,cell cycle,cell-cell tight junctions,viral carcinogenesis,microRNAs in cancer,etc.The protein interaction network mainly focused on DDX17,NCL,EEF2,CDK1,SSRP1,and SMARCC1.The statistical findings unveiled the up-regulated changes in the two omics of SKP1,ORC1,and BAD and the down-regulated changes in RBL1,RB1,CDK1,CDC6,MCM4,TFDP1,CHD4,and SNW1.Moreover,the phosphorylation differences were more significant than the protein differences.Conclusion RAI16 plays the possible crucial role in multiple biological functions and signaling pathways through key proteins,such as SKP1,ORC1,RB1,and CDK1,which affect the cell cycle and thereby the occurrence and development of cancer.
3.Multi-Node Data Fusion Method of Home Health Monitoring Equipment for Assisting TCM Diagnosis
Qicheng YANG ; Chuanbiao WEN ; Yibo ZHOU ; Tao YANG ; Junying ZHU ; Ji LUO ; Ju CHEN
World Science and Technology-Modernization of Traditional Chinese Medicine 2024;26(5):1344-1353
Objective To solve the problem of large data volume,multiple dimensions and low value for assisting traditional Chinese medicine clinical diagnosis in home health perception layer devices.Methods Based on the principles of traditional Chinese medicine diagnosis,this paper divides home health data into three types:complementary,redundant,and collaborative,and proposes a solution for data fusion at the levels of device data,home events,and traditional Chinese medicine symptoms.Results The proposed data fusion solution in this paper enables the data collected by various devices in the home environment to work together,extracts home data that is more valuable for traditional Chinese medicine diagnosis,and reduces the real-time pressure on the home network bandwidth caused by the sensors on the home side.Conclusion The construction of an open IoT ecosystem for home health based on multiple devices is a huge project,which includes the construction of perception layer hardware,data cleaning,fusion,normalization,labeling,modeling,and other aspects.This paper focuses on the idea of home health data fusion,which can provide directions for cleaning up heterogeneous data from multiple sources at home and also provide ideas for subsequent data labeling and modeling with traditional Chinese medicine characteristics,thus providing more valuable decision-making assistance for traditional Chinese medicine clinical practice.
4.Predictive value of multimodal ultrasound for upper urinary tract damage in children with neurogenic bladder
Junkui WANG ; Miao WANG ; Zikai LI ; Qinghua QI ; Yibo WEN ; Zhibin WU ; Xinghuan YANG ; Jianguo WEN
Chinese Journal of Applied Clinical Pediatrics 2024;39(12):911-916
Objective:To explore the predictive value of multimodal ultrasound (MMU) for upper urinary tract damage (UUTD) in children with neurogenic bladder (NB).Methods:This was a case-series study.From January 2022 to December 2023, 87 children with NB admitted to the First Affiliated Hospital of Zhengzhou University were examined by MMU.During the filling of bladder, vesical volume (VV), bladder wall thickness (BWT), shear wave velocity (SWV) of the anterior wall, resistance index (RI), and vascularization index (VI) were measured.After the emptying of bladder, VV and anterior wall SWV were measured, and ultrasound bladder compliance (△C) was calculated.The anterior posterior diameter (APD) of the renal pelvis and ureteral diameter (UD) were also measured.According to the upper/lower urinary tract dysfunction classification criteria, NB children were divided into a UUTD group and a non-UUTD (NUUTD) group.The differences in clinical data and related examinations between the 2 groups were analyzed to screen out independent risk factors, and an early warning model was established based on these factors.The prediction efficiency of the model and the urodynamic study (UDS) for UUTD was compared.Results:(1) There were 47 children in the UUTD group and 40 children in the NUUTD group.There was no significant difference in gender, age and body mass index between the 2 groups (all P>0.05).(2) In the UUTD group, the total glomerular filtration rate (tGFR) was (70.45±16.17) mL/min, the incidence of hydronephrosis was 38.30%, and the incidence of ureteral dilatation was 23.40%.No morphological changes were found in the imaging examination of the urinary system in the NUUTD group, and its tGFR was (100.55±16.27) mL/min.There was a significant difference in tGFR between the 2 groups ( P<0.05).(3) The filling VV, emptying VV, mean BWT, filling SWV, emptying SWV, VI, mean RI, △C, maximum cystometric capacity (MCC), maximum detrusor pressure during filling (Pdet.max), bladder compliance (BC), and detrusor leak point pressure (DLPP) in the NUUTD group were (218.43±87.53) mL, (14.62±6.14) mL, (3.08±0.65) mm, (2.64±0.54) m/s, (1.88±0.41) m/s, (6.20±1.04)%, 0.68±0.04, (147.58±49.18) mm 2·s, (309.50±66.54) mL, (59.83±19.79) cmH 2O(1 cmH 2O=0.098 kPa), (25.80±10.34) mL/cmH 2O, and (34.00±6.16) cmH 2O, respectively.Compared with the NUUTD group, the UUTD group showed decreased filling VV [(167.21±85.63) mL], △C [(78.49±31.86) mm 2·s], VI [(5.01±0.81) %], MCC [(255.32±75.10) mL], and BC [(12.57±6.44) mL/cmH 2O], and increased emptying VV [(19.50±7.65) mL], mean BWT [(4.02±0.82) mm], filling SWV [(3.99±1.07) m/s], emptying SWV [(2.15±0.35) m/s], mean RI (0.70±0.08), Pdet.max [(75.94±26.23) cmH 2O], and DLPP [(48.13±12.61) cmH 2O] (all P<0.05).(4) The decreased BC ( OR=0.841, 95% CI: 0.562-1.256, P=0.045), △C ( OR=0.427, 95% CI: 0.202-0.904, P=0.026) and VI ( OR=0.461, 95% CI: 0.091-2.325, P=0.010) and the increased DLPP ( OR=1.139, 95% CI: 0.894-1.451, P=0.040), filling SWV ( OR=1.895, 95% CI: 1.082-3.321, P=0.007) and mean BWT ( OR=1.191, 95% CI: 0.850-1.669, P=0.025) were independent risk factors for UUTD.Among MMU parameters, filling SWV had the highest prediction efficiency for UUTD, with a threshold of 3.33 m/s, sensitivity of 72.34% and specificity of 92.50%. Conclusions:MMU can well predict the occurrence of UUTD in children with NB, and filling SWV has the highest prediction efficiency.
5.Correlation between triglyceride-glucose index and high on-treatment platelet reactivity during clopidogrel treatment in patients with ischemic stroke
Haoxuan CHEN ; Li YANG ; Zhenzhen LOU ; Yibo ZHAN ; Huiying OUYANG ; Guixian CHEN ; Changlin ZHANG ; Hui MAO ; Xiaojun LI ; Zhiping HUANG ; Zequan ZHENG ; Haoyou XU ; Longlong WEN ; Min ZHAO ; Yuanqi ZHAO
International Journal of Cerebrovascular Diseases 2023;31(4):253-258
Objective:To investigate the correlation between triglyceride-glucose (TyG) index and high on-treatment platelet reactivity (HTPR) during clopidogrel treatment in patients with ischemic stroke.Methods:Patients with ischemic stroke who received maintenance dose of clopidogrel (75 mg/d) in the Department of Neurology, Guangdong Provincial Hospital of Chinese Medicine from January 2017 to March 2021 were retrospectively included. The highest quartile (Q4) of the TyG index was defined as insulin resistance. Platelet reactivity was assessed by thromboelastogram and clopidogrel HTPR was defined as the clot strength induced by adenosine diphosphate (MA ADP) >47 mm. Multivariate regression model was used to analyze the independent correlation between TyG index and platelet reactivity. Results:A total of 83 patients were included. The TyG index showed a linear correlation with MA ADP. The patients were divided into 4 groups according to the quartile of TyG index. The incidence of clopidogrel HTPR increased significantly with the increase of the quartile of the TyG index ( Ptrend=0.017). Multivariate analysis showed that there was a significant independent correlation between insulin resistance and clopidogrel HTPR (odds ratio 4.597, 95% confidence interval 1.285-16.446; P=0.019). Conclusions:In patients with ischemic stroke treated with clopidogrel, the incidence of clopidogrel HTPR gradually increases with the increase of the quartile of the TyG index. The insulin resistance assessed by the TyG index is independently associated with clopidogrel HTPR.
6.Sports and health integration: logic, dilemma and alleviation
Yanfeng ZHANG ; Yibo GAO ; Sen LI ; Zhaoyong WEN ; Aoyu ZHANG ; Jin HE
Chinese Journal of Behavioral Medicine and Brain Science 2023;32(6):481-487
By combing out the historical development logic of sports and health integration and the current development achievement, the underlying logic of sports and health integration is described systematically in multiple dimensions, and the prominent dilemmas in development are analyzed as follows: lack of residents' health literacy, excessive dependence on medical treatment, low bridging of talent team construction, lack of the guidance of funds centralization, insufficient financial support, imperfect management system and mechanism, and unspecific departmental collaboration.The strategies for solving the problems are as follows: strengthening the integration of sports science and clinical medicine, consolidating the technical integration of sports prescription and clinical standardization process, further improving the business integration of exercise intervention and clinical treatment, and enhancing the industrial integration of sports products and medical treatment.
7.Mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes caused by mitochondrial DNA 14453G>A mutation: a case report and literature review
Yibo REN ; Yu LONG ; Zhongkai ZHOU ; Jue ZHONG ; Shirong WEN ; Yujun PAN ; Ruohan SUN
Chinese Journal of Neurology 2023;56(10):1158-1165
Objective:To explore the clinical and imaging characteristics of mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes (MELAS) caused by mitochondrial DNA 14453G>A (m.14453G>A) mutation.Methods:A case of MELAS caused by m.14453G>A mutation in the First Affiliated Hospital of Harbin Medical University on October 12, 2021 was reported. At the same time, the reported cases of MELAS and Leigh syndrome (LS) caused by the m.14453G>A mutation were reviewed. This enabled a comprehensive summarization, analysis, and comparison of these cases.Results:The patient was a female. She has suffered from the disease since 13-year old with seizures, accompanied by the disturbance of mood and the loss of memory. Brain magnetic resonance imaging findings consisted of lesions in frontal, parietal, occipital, temporal lobe and cerebellar. The patient was initially considered with autoimmune encephalitis and posterior reversible encephalopathy syndrome. Since direct sequencing of the complete mitochondrial genome from blood of the patient revealed m.14453G>A mutation in ND6 gene, and the mutation rate was 17.0%, the patient eventually diagnosed with MELAS based on clinical manifestations, imaging examinations, and genetic testing results. Using "m.14453G>A" as the search term, the relevant literature in China and abroad was retrieved and those with complete clinical data were identified. A total of 11 cases of m.14453G>A mutation including this case were reported, of whom 5 patients were diagnosed as MELAS, and 6 patients were diagnosed as LS. Among the 11 patients, those being adolescent or adult and with lesions in the cortex and subcortical white matter were probably be MELAS; those being infant or young child and with lesions in basal ganglia, thalamus and brainstem could be LS. Conclusions:Mitochondrial disease caused by m.14453G>A gene mutation shows a great heterogeneity, which can cause MELAS and LS. The clinical phenotype of the m.14453G>A mutation may be related to the age of onset and lesion′ s location.
8.The change of serum complement factor B and its clinical implication in children with primary IgA nephropathy
Lu WEN ; Fengping JI ; Yibo WEN ; Xiaoyang WANG ; Zhanzheng ZHAO
Chinese Journal of Applied Clinical Pediatrics 2021;36(24):1882-1886
Objective:To detect serum level of complement factor B (CFB), and to explore its correlations with clinical parameters and prognosis in children with primary IgA nephropathy (IgAN).Methods:A total of 204 children with primary IgAN confirmed by kidney biopsy in the Department of Nephrology of the First Affiliated Hospital of Zhengzhou University from December 2014 to April 2017 were included in IgAN group.During the same period, 84 healthy children were included in healthy control group.Their mean age was (11.0±3.5) years and (10.9±3.2) years, respectively.Patients in IgAN group were divided into low CFB group (102 cases) and high CFB group (102 cases) according to the medium serum level of CFB measured by enzyme-linked immunosorbent assay. Spearman′ s coefficient was employed to analyze correlation amongst various parameters.Multivariable-adjusted Cox proportional ha-zards models were used to evaluate the relationship between serum CFB level and prognosis in children with IgAN. Results:Serum CFB levels were significantly higher in IgAN group than that in healthy control group [290.9 (186.2-453.9) mg/L vs.218.9 (155.0-321.3) mg/L, Z=-3.372, P=0.001]. Serum levels of CFB were negatively correlated with serum albumin ( r=-0.388, P<0.001) and estimated glomerular filtration rate ( r=-0.416, P<0.001), but positively correlated with serum creatinine ( r=0.305, P<0.001) and 24 h urinary protein ( r=0.456, P<0.001) in IgAN group.The incidences of crescents (C1-2) (70.6% vs.29.4%, χ2=34.588, P<0.001) and C 3 deposition (+ + -+ + + ) (63.7% vs.44.1%, χ2=7.892, P=0.005) were significantly higher in high CFB group than those in low CFB group. Kaplan- Meier analysis showed that high CFB levels predicted worse renal outcome in pediatric IgAN patients ( χ2=17.509, P<0.001). Multivariate Cox regression analysis showed that the high CFB level was the independent risk factor for the poor renal outcome ( HR=2.517, 95% CI: 1.284-4.932, P=0.007). Conclusions:High serum levels of CFB are associated with decreased renal function, increased urinary protein excretion, crescentic formation and poor renal outcome in pediatric IgAN patients.
9.Changes in serum C3d and C5b-9 levels in elderly patients with idiopathic membranous nephropathy and their clinical significance
Lu WEN ; Fengping JI ; Yibo WEN ; Xiaoyang WANG ; Zhanzheng ZHAO
Chinese Journal of Geriatrics 2021;40(10):1245-1249
Objective:To investigate changes in serum C3d and C5b-9 levels in elderly patients with idiopathic membranous nephropathy(IMN)and their correlations with prognosis.Methods:Two hundred thirty-one elderly patients with IMN and 96 non-elderly patients with IMN confirmed by kidney biopsy at the First Affiliated Hospital of Zhengzhou University from January 2015 to May 2017 were enrolled.During the same period, 118 healthy individuals receiving health checkups were included as controls.Patients were divided into the low C3d group( n=112)and the high C3d group( n=113)according to the median level of serum C3d.Serum C3d and C5b-9 levels were measured by enzyme-linked immunosorbent assays. Results:Serum C3d and C5b-9 levels in elderly IMN patients were 0.23(0.15, 0.45)mg/L and 0.28(0.20, 1.23)mg/L, respectively, which were higher than those in healthy controls[0.18(0.13, 0.22)mg/L, 0.22(0.16, 0.26)mg/L, respectively]( Z=-4.261 and -6.213, P<0.001). Serum C3d levels in elderly and non-elderly IMN patients were correlated negatively with the estimated glomerular filtration rate( r=-0.155 and -0.426, P=0.019 and 0.000), but positively with serum creatinine, anti-phospholipase A2 receptor(PLA2R)antibody levels and 24 h urinary protein( r=0.184, 0.326, 0.407, 0.321 and 0.145, P=0.005, 0.001, 0.000, 0.001 and 0.027). Kaplan-Meier survival analysis showed that the cumulative renal survival rate in elderly IMN patients was lower in the high C3d group than in the low C3d group(47.8% vs.70.8%, Log Rank χ2=7.399, P=0.007). Multivariate Cox regression analysis showed that high C3d levels were an independent risk factor for poor renal outcomes in elderly IMN patients( HR=2.288, 95% CI: 1.082-4.839, P=0.030). Conclusions:High serum C3d levels are associated with increases in urinary protein excretion and anti-PLA2R antibody levels, renal function decline, and poor renal outcomes in elderly IMN patients.
10.Effect of erythropoietin on the eXpression and function of renal aquaporin-1 after release of bilateral ureter obstruction in young rats
Xi GUO ; Jinjin FENG ; Shaohua YAN ; Yibo WEN ; Jianguo WEN
Chinese Journal of Applied Clinical Pediatrics 2019;34(5):347-351
Objective To investigate the effect of erythropoietin(EDO)on the expression and function of aqua_porin_1( AQD _1)in the kidney of young male SD rats after release of bilateral ureter obstruction( BUO _ R). Methods Porty_eight young SD rats were randomly divided into bilateral ureteral complete obstruction(BUO)group (n﹦6),BUO_R group(n﹦12),BUO_R﹢EDO group( n﹦12)and Sham group( n﹦18). The BUO model was built through bilateral ureteral ligation. BUO group were killed after 24 h,and BUO_R group and BUO_R﹢EDO group were relieved after obstruction of 24 h. EDO(500 U∕kg)was given to BUO_R﹢EDO rats at 1 h after release of BUO,and then repeated 1 d,3 d and 5 d thereafter and the same volume of 9 g∕L saline was simultaneously given to BUO_R rats. The Sham group was prepared in parallel by laparotomy and free dissection of bilateral ureters but not ligated,both side kidneys and blood samples were collected on 3 d and 7 d(24 h,3 d,7 d for Sham group)after release of BUO. The u_rine samples were collected by using metabolic cage before death. The plasma osmotic pressure,creatinine(Cr)and u_rea nitrogen(BUN)in the plasma of young rats were detected. The expression of AQD_1 protein in all groups of kidney tissues was detected by adopting immunohistochemistry and Western blot. Results On day 3 after release of BUO,24 h water intake and urine volume of BUO_R﹢EDO group were higher than those of Sham group,but lower than those of BUO group(P〈0. 05),the urine osmotic pressure of BUO_R﹢EDO group was higher than that of BUO group,but lower than that of Sham group(P〈0. 05),while plasma osmotic pressure,Cr and BUN of BUO_R﹢EDO group were higher than those of Sham group,but lower than those of BUO group(P〈0. 05),and they were all of lower than BUO group( P 〈0. 05). On day 7 after release of BUO,there was no obvious change in Sham group,and the indexes of BUO_R group and BUO_R﹢EDO group gradually recovered,but they still did not reach the normal level(P〈0. 05). The difference between BUO_R group and BUO_R﹢EDO group was statistically significant(P〈0. 05). The immuno_histochemical results showed that the expression of AQD_1 in collecting duct in BUO group was significantly down_regulated compared with that in Sham group,whereas it was slightly weaker in BUO_R group and BUO_R﹢EDO group than that of Sham group(P〈0. 05). Compared with 3 days after release of BUO,the staining intensity of BUO_R﹢EDO group and BUO_R group was enhanced,but still lower than that of the Sham group. These results were further confirmed by adopting Western blot,and BUO group was also the lowest of the four groups,and BUO_R﹢EDO group was higher than that of BUO group,but lower than that of Sham group( P〈0. 05). Conclusion EDO can promote not only the recovery of AQD_1 protein expression but also the recovery of renal function in young BUO_R rats.

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