1. Advances in pathogenesis of minimal change nephrotic syndrome
Shiqiu XIONG ; Xiqiang DANG ; Qingnan HE
International Journal of Pediatrics 2019;46(12):864-868
Minimal change nephrotic syndrome (MCNS) is the most common nephrotic syndrome among children.Although the details of pathogenesis remain unknown, it is widely considered that upregulated expression of T lymphocyte cell cytokines contributes to the initiation of MCNS.Moreover, studies had revealed that altered number and function disorder of B lymphocyte cells could change the functions of antigen presentation, participating in the onset of MCNS by affecting the function of T lymphocyte cells.Recently, CD80 has emerged as a popular research topic which exerts its effects via the change of podocytes morphology, thereby affecting the glomerular permeability.However, neither immune disorder nor podocyte dysfunction is poorly demonstrated to be associated with the pathogenesis of MCNS, the hypothesis such as "a 'two hit disorder" and "γδT cells exacerbate podocyte injury via the CD28/B7-1-phosphor-SRC kinase pathway" are raised.In the current review, we summarized the related investigations to help us to understand the mechanisms and pathogenesis of MCNS.
2.Correlation between vascular damage and blood myocardin in children with lupus nephritis
Chunyan NING ; Xiqiang DANG ; Fang SONG ; Zhuwen YI ; Xiaojie HE
Journal of Clinical Pediatrics 2016;34(10):761-766
Objective To investigate the changes in the concentration of myocardin in children with lupus nephritis (LN) under different degree of vessel damage.Methods Forty-nine children diagnosed with LN by routine tissue immunolfuorescence, light microscope, and electron microscope were included, and 30 healthy children were included as control group. The pathological classiifcations were performed according to the ISN/RPS 2003 LN pathological classiifcation criterion. According to the Katafuchi evaluation method, the semi quantitative assessment of glomerular and kidney tubule damage was carried out, and the degree of vascular damage was evaluated at the same time. Double antibody sandwich method was used to detect the concentration of serum myocardin.Results The glomerular and kidney tubules damage in children with LN were signiifcantly aggravated with higher pathological classification (P<0.05). Glomerular damage was positively correlated with renal interstitial damage (r=0.96, P<0.01). The degree of vascular damage was related to the degree of glomerular injury and renal interstitial injury, while it was no related with the results of clinical tests. There were different concentrations of myocardin among mild-, moderate-, severe-vessel damage and control groups (F=378.61,P<0.001), and the concentration of myocardin in moderate- and severe-vessel damage groups were obviously lower than those in control group and mild-vessel damage group (P<0.01) while there was no difference between control group and mild-vessel damage group (P>0.05). According to pathological type, there were signiifcant differences in the concentration of myocardial between control group and different pathological types (F=626.793,P<0.01). FromⅡ,Ⅲ,Ⅲ+Ⅴ,Ⅳ toⅣ+Ⅴ, the concentrations of myocardial were decreased systematically, and there were statistic differences between groups (P all<0.05).Conclusion The concentration of myocardin in children with LN can relfect the renal vascular damage to a certain extent. Elevation of myocardin concentration may be helpful for the repair of vascular damage.
3.Protective effect of rhein on aristolochic acid-induced renal injury in zebrafish
Xue WANG ; Kechun LIU ; Ximin WANG ; Liwen HAN ; Shanshan ZHANG ; Qiuxia HE ; Xiqiang CHEN ; Jian HAN ; Rongchun WANG
Chinese Pharmacological Bulletin 2016;32(3):361-365
Aim To study the effect of rhein on renal damage induced by aristolochic acid. Methods Ze-brafish model of aristolochic acid nephropathy, genera-ted by treating zebrafish larvae with aristolochic acid for 24 h, was treated with rhein simultaneously . Mor-pholigical changes were observed and the creatinine level in larvae tissue was measured. And mRNA ex-pression levels of inflammatory factor cox2 a and fibrosis factor TGF-β1 in larvae tissue were detected using qPCR. Results Some larvae show periocular edema and circulation system defection e. g. weak heart beat, narrow cardiac vesicle, decreased blood flow and even blockage , with a dose-response relationship after expo-sure to aristolochic acid for 24 h. The creatinine level in larvae tissue of the treated group was significantly higher than that of the control larvae. And the expres-sion levels of cox2 a and TGF-β1 in larvae tissue of the treated group were also significantly increased. Per-centage of abnormal larvae and creatinine level in lar-vae tissue were decreased when treated with rhein sim-ultaneously. And the expression levels of cox2a was down-regulated by rhein compared with the aristolochic acid treated group. But rhein had no effect on TGF-β1 expression. Conclusion To some extent rhein can protect renal from damage induced by aristolochic acid.
4.Expression of EB virus in peripheral blood mononuclear cells in children with systemic lupus erythematosus
Yan DING ; Xiaojie HE ; Wang LIAO ; Huilan YANG ; Wei XIANG ; Xiqiang DANG ; Zhuwen YI
Chinese Journal of Applied Clinical Pediatrics 2015;30(7):513-516
Objective To discuss the role of EB virus (EBV)in the pathogenesis of systemic lupus erythematosus(SLE) in children through investigating the copies of EBV DNA and expression of EBV genes in peripheral blood mononuclear cells(PBMCs).Methods (1)PBMCs were isolated from 30 patients with SLE and 12 healthy normal controls respectively and DNA was extracted from PBMCs.(2) PBMCs were co-cultured with EBV for 12 days and RNA was extracted from PBMCs.(3)Real-time fluorescence quantitative PCR(Real-time PCR) was applied to detect the copies of EBV DNA in PBMCs.(4)Reverse transcription PCR was applied to detect expression of EBV genes.Results (1) Compared with the healthy control group [(40.1 ± 11.6) copies/μg],a significant increase of EBV DNA copies was observed in SLE group[(658.6 ± 183.6) copies/μg] (P <0.05).The EBV DNA copies in the active SLE group [(785.2 ± 179.2) copies/μg] were significantly higher than those in the non-active SLE group [(586.0 ± 193.1) copies/μg] (P < 0.05).(2)There was no correlation between EBV DNA copies and systemic lupus erythematosus disease activity index (r =0.03,P > 0.05).(3) After PBMCs got co-cultured with EBV,expression of latent EBV genes and lytic genes were both increased in the patients and healthy controls.The latent EBV genes including latent membrane protein 1 (LMP1),LMP2,EBV nuclear antigen 1 and the lytic genes including BCRF1,BLLF1 were all increased significantly in the patients compared with the healthy controls (all P < 0.05).Conclusions There is a significant increase of EBV DNA copies and aberrant expression of EBV genes in SLE patients,which suggests that EBV may contribute to the pathogenesis of SLE.
5.Aberrant expression of Epstein-Barr virus genes in children with systemic lupus erythematosus
Yan DING ; Xiaojie HE ; Wang LIAO ; Huilan YANG ; Wei XIANG ; Xiqiang DANG ; Zhuwen YI
Chinese Journal of Dermatology 2015;48(1):15-18
Objective To investigate the expression and significance of Epstein-Barr virus (EBV) genes in children with systemic lupus erythematosus (SLE).Methods Peripheral blood mononuclear cells (PBMCs) were isolated from 20 children with SLE and 12 healthy human controls.Enzyme-linked immunosorbent assay (ELISA) was conducted to detect anti-EBV viral capsid antigen (VCA) IgG/IgM antibodies.The culture supernatants of cells from patients with anti-EBV VCA IgG/IgM antibodies were collected,and PBMCs from the patients and controls were co-cultured with the supernatants respectively for 12 days.RNA was extracted from PBMCs before and after the coculture,and reverse transcription-PCR was performed to detect the expression of EBV genes,including LMP1,LMP2,EBNA1,BCRF1,BLLF1 and BILF1 genes.Results LMP1 gene was detected in fresh PBMCs from 10 out of 20 patients and 1 out of 12 controls (P < 0.05).No significant differences were observed between the patients and controls in the detection rate of LMP2 gene (4/20 vs.1/12),EBNA1 gene (13/20 vs.3/12),BCRF1 gene (3/20 vs.1/12) or BLLF1 gene (5/20 vs.2/12) in fresh PBMCs.After co-culture with the supernatants of cells from patients with anti-EBV VCA IgG/IgM antibodies,the expressions of EBV genes in these PBMCs were increased to different degrees,and there was a significant difference in the expressions of EBV latent genes LMP1,LMP2 and EBNA-1 as well as EBV replicative genes BCRF1 and BLLF1 between the patient-derived and control-derived PBMCs (all P < 0.05).Conclusions There is an aberrant expression of EBV genes in children with SLE,and EBV genes may contribute to the development of SLE.
6.Research development of newborn acute kidney injury
Jianqiu LI ; Qin YANG ; Xiqiang DANG ; Qingnan HE
Chinese Journal of Applied Clinical Pediatrics 2014;29(17):1345-1348
The incidence of acute kidney injury(AKI) in neonate is not low,it occurs in many cases such as ischemic-hypoxic injury,infection,administration of nephrotoxicity drugs and urinary tract obstruction,of which perinatal asphyxia ranked first in China.Due to the severe food security crisis,the occurrence of urinary tract obstruction is rising in recent years.The child health care should pay attention to prevent and screen this kind of disease for the high risk group.The diagnosis of AKI is difficult for newborn because serum creatinine and urine are hard to make a definite boundary.So study of early markers of AKI seems to be of great importance,of which neutrophil gelatinase associated lipocalin and cystatin C are research focuses,treatments should aim at solving primary disease such as ischemic,and so on.Renal replacement therapy is recommended when it comes to severe cases,but mortality still remains high,corresponding to severe primary disease and complications.
7.Influence of CATS and Cell Saver on hemorheology and blood quality of intraoperative cell salvage in orthopaedic surgery
Nawan AYSHA ; Xiqiang HE ; Shizhong LI
Chongqing Medicine 2014;(35):4740-4742,4745
Objective To observe recycle homorheology index of two autologous blood recover machines in orthopedic operation , including maximum deformation index (DImax) ,aggregation index(AImax) ,osmotic fragility ,hematocrit(Hct) ,hemoglobin(Hb) , blood electrolytes and pH value ,the changes of in vivo Hct ,Hb ,blood electrolyte and pH value after the autotransfusion to provide references for rational clinical use of cell salvage .Methods Seventy‐six patients were randomly divided into group A (CATS) and group B (Cell Saver) ,38 cases in each group .Autologous test of DImax ,AImax ,osmotic fragility ,Hct ,Hb ,blood electrolytes ,pH value and Hct ,Hb ,osmotic fragility ,pH value of patients before and after autotransfusion ,24 h after operation ,used to determine the in vivo salvaged were measured .Results DImax of group A were lower than that of group B with no difference(P<0 .05);AImax of both groups had no different(P>0 .05) ,but was lower than the reference value .RBC osmotic fragility curve shifted to the right in group A ,each index was significantly lower than its reference value(P<0 .05) .The in vivo Hct ,Hb ,K+ of group A were significantly higher than that of group B ,Na+ level of group A was lower than of group B ,each index had significantly difference with its reference value(P<0 .05) .pH value of both groups was slightly alkaline .The in vivo Hct ,Hb ,K+ ,Na+ level and pH value of both groups had no difference at the point of before and immediately after autotransfusion and 24 h postoperatively ,there were no statistically difference(P>0 .05) .The in vivo Hct of both groups after autotransfusion were significantly higher than before(P<0 .05) .Conclusion The hemorheology index and quality of salvaged blood acquired from these two cell salvage systems in orthopae‐dic operation have no obvious differences .The function of these two kinds of cell salvage systems is safer and reliable .
8.The renal pathological change of 31 Henoch-Sch(o)nlein purpura with normal urine routine
Yanlan ZHONG ; Xiqiang DANG ; Xiaojie HE ; Zhuwen YI ; Qingnan HE
Journal of Chinese Physician 2012;14(3):322-324
Objective To research Henoch-Schonlein purpura purpura (HSP) and renal pathology in children.Methods 31 hospitalized HSP children that with normal urine routine and accepted renal biopsy in our hospital.Results There were different levels of kidney pathological damage in this group of 31 cases,the results of light microscope were from grade Ⅱ to grade Ⅵ The proportion was grade Ⅱ(35.48%,11 of 31),grade Ⅲ (54.83%,17 of 31),and grade Ⅳ,Ⅴ and Ⅵ (each 1 case of 31,3.23% ).lmmunofluorescence pathology results were showed as following:merely IgA depositional (48.38%,15 of 31 ),IgA + IgG depositional ( 19.36%,6 of 31 ),IgA + IgM depositional ( 19.36%,6of 31 ),IgA + igG + IgM depositional ( 12.90%,4 of 31 ).Microalbuminuria had been founded in 14 cases,and the microalbuminuria level of 10 cases were higher than normal value( 10 of 14,71.43% ).Conclusions HSP children had renal pathologic dysfunction,even the urine routine were normal,and the detection of urine microalbumin was a significant marker in the early stage.
9.Fluticasone increased Foxp3 in childhood asthma with upregulation of phosphorylated STAT5
Yun HE ; Xiaohong XIE ; Yu DENG ; Xin LI ; Zhou FU ; Xiqiang YANG ; Enmei LIU
Journal of Clinical Pediatrics 2011;(1):1-7
Objective To evaluate the effects of fluticasone propionate (FP)on Foxp3 expression in CD4+T cells, to explore the possible mechanisms of childhood asthma. Methods Thirty asthmatic children, 15 with inhaled FP and 15 without inhaled FP, and 16 healthy children were recruited. Peripheral blood mononuclear cells (PBMC)labeled for CD4 and intracellular Foxp3 were analyzed using flow eytometry. The levels of IL-2 and IL-6 in serum and supernatant before and after stimulation by Phytohemagglutination (PHA)were measured by ELISA. The expression of phosphorylated signal transducer and activator of transcription 5 (STAT5)in PBMC was detected by Western-blot.Results Compared with healthy control, the percentage of CD4+ Foxp3+ cells in PBMC in asthmatic children without inhaled FP was significantly decreased. After inhaled FP and in remission stage, the percentage of CD4+ Foxp3+ cells in asthmatic children was up regulated with a decreased serum IL-6 level and an increased phosphorylated STATS expression. Conclusions Decreased Foxp3 protein expression in peripheral CD4+ T regulatory cells (Treg)is characterized in childhood asthma. Inhaled glucoeorticoid therapy of childhood asthma might be attributed to its ability of increasing Foxp3 expression by upregulation of phosphorylated STAT5 to balance the T cell response.
10.Renal interstitial microvascular density and calcium-sensing receptor expression in children with steroid-resistant nephrotic syndrome
Jianhui QIU ; Hong TAN ; Xiaojie HE ; Xiqiang DANG ; Zhuwen YI
Journal of Chinese Physician 2011;13(8):1009-1013
ObjectiveStudy the relationship among CaSR expression, tubulointerstitial damage,metabolic disturbance of calcium and phosphorus and microvascular density around the tubulointerstitium in children with steroid-resistant nephrotic syndrome.Methods36 cases of children with primary nephrotic syndrome were divided into hormone-sensitive group and steroid-resistant group.Semi-quantitative scores for tubulointerstitial pathological evaluation of the extent of damage, automatic biochemical analyzer for the determination of serum calcium (Ca), phosphorus (P) concentration of renal tubular epithelial CaSR expression and microvessel microvascular density around the tubulointerstitium were determined by immunohistochemical assay.ResultsMore severe the tubulointerstitial damage, lower level of serum Ca and higher level of serum P were observed [(2.26 ± 0.15) mmol/L]in children of the steroid-resistant group and the steroid-sensitive group [(1.90 + 0.12) mmol/L, P < 0.05].CaSR expression (4.63 + 0.78) of renal tubular epithelial cells in the steroid- sensitive group was significantly lower than that in the steroid-resistant group (6.56 + 1.22, P < 0.05), but microvascular density was significantly higher in the steroid- sensitive group(2.98 +0.35 vs 2.02 +0.24, P <0.05).When the tubulointerstitial damage was mild, CaSR expression (4.15 +0.58) in renal tubular epithelial cells in the steroid- sensitive group (4.26 ±0.61) was lower than the steroid-resistant group(3.12 ± 0.33; 3.01 ± 0.21), and microvascular density was higher,but the difference was not significant(P >0.05).In the moderate tubulointerstitial damage, CaSR expression in renal tubular epithelial cells in the steroid- sensitive group (5.35 ± 0.64) was significantly lower than the resistant group (7.37 +0.81, P <0.01), and microvascular density was significantly higher than the resistant group (2.81 ±0.16, 2.02 ±0.14, P <0.05).Compared by mild and moderate tubulointerstitial damage in children with the steroid-resistant, CaSR expression (11.46 ± 1.38) in children with severe tubulointerstitial damage was significantly increased, and microvascular density (1.15 ± 0.11) was significantly decreased (all P < 0.01).ConclusionsCaSR expression was increased and microvascular density around the tubulointerstitium was decreased in children with steroid-resistant nephrotic syndrome.Dut to steroid resistance, the cytotoxic of steroid damaged the renal tubular epithelial cells, the metabolic disturbance of calcium and phosphorus and the damage of blood vessel endothelium finally resulted in severe tubulointerstitial damage.

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