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Objective:To investigate the role of the NOD-like receptor thermal protein domain associated protein 3(NLRP3)inflammasome and its downstream interleukin(IL)-1β, IL-6, and IL-18 in the pathogenesis of antineutrophil cytoplasmic antibody-associated vasculitis(AAV) in children.Methods:A retrospective study was conducted.Specifically, the localization and expression of the NLRP3 inflammasome in renal tissues of 22 children who were diagnosed with primary AAV and underwent renal biopsy in the Department of Pediatric Nephrology and Rheumatology, the First Affiliated Hospital of Sun Yat-Sen University from September 2003 to September 2020 were detected by the immunohistochemical method.The IL-1β, IL-6 and IL-18 levels in serum and urine were measured by enzyme-linked immunosorbent assay.The measurement data conforming to normal distribution were compared by the t test between two groups and by the single factor ANOVA test among multiple groups.The measurement data that did not conform to normal distribution were compared by the Wilcoxon signed rank sum test.Classification variables were examined by the χ2 test. Pearson correlation coefficient or Spearman rank correlation coefficient were used to analyze the correlation among variables. Results:NLRP3 was widely expressed in the tubulointerstitium, and the expression level in the active group was higher than that in the control group, the semi-quantitative scores of NLRP3 in the renal tubule and glomeruli in the active group were higher than those in the control group ( F=0.859, 8.320, all P<0.05). In the active group, the semi-quantitative score of NLRP3 in the renal tubule was higher than that in the glomeruli( F=3.517, P<0.05). The semi-quantitative score of NLRP3 in the renal tubule was positively correlated with the pediatric vasculitis activity score at renal biopsy ( r=0.471, P=0.027)and negatively correlated with the estimated glomerular filtration rate at renal biopsy ( r=-0.548, P=0.008)in the active group.The serum IL-1β, serum IL-18 and urinary IL-6 levels in the active group were higher than those in the remission group and the control group ( F=16.449, 16.449, 0.637, 29.891, 27.612, 7.464, all P<0.05). The serum IL-18 level in the remission group was higher than that in the control group( F=18.671, P<0.05). In the active group, a positive correlation was found between the serum IL-1β level and the semi-quantitative score of NLRP3 in the renal tubule( r=0.805, P=0.002), between the serum IL-6 level and the C-reactive protein level at renal biopsy ( r=0.728, P=0.017), and between the urinary IL-6 level and the crescent proportion at renal biopsy ( r=0.677, P=0.032). The serum IL-18 level in the active group was positively correlated with the semi-quantitative score of NLRP3 in the renal tubule, pediatric vasculitis activity score and glomerular sclerosis proportion at renal biopsy, and negatively correlated with the estimated glomerular filtration rate at renal biopsy ( r=0.644, 0.612, 0.695, -0.577, all P<0.05). The urinary IL-18 level was positively correlated with the complement C 4 level at renal biopsy ( r=0.855, P<0.05). Conclusions:The NLRP3 inflammasome and its downstream IL-1β, IL-6, and IL-18 may be involved in the pathogenesis and progression of AAV, and can be used as one of the reference indicators for disease activity assessment.
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Objective:To explore clinicopathological features and prognosis of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) in children induced by antithyroid drugs.Methods:The clinicopathological features, treatment and prognosis of 3 children with AAV induced by antithyroid drugs in the Department of Pediatric Nephrology and Rheumatology of the First Affiliated Hospital of Sun Yat-sen University were analyzed retrospectively, and the literatures were reviewed.Results:(1) Among the 3 cases, there were 2 females and 1 male, whose ages were 12.6, 13.9 and 13.1 years old, respectively. All patients had medication history of propylthiouracil (PTU) and/or methimazole (MMI) before onset. Initial manifestation was pallor and renal involvements with nephrotic proteinuria, hematuria and renal function abnormality, while 2 of them had hypertension. Extrarenal manifestations were also presented: case 1 presented with rash, arthralgia and cardiac insufficiency; case 2 had brain involvement with repeated convulsions; case 3 presented with arthralgia and lung involvement. They were all tested positive for p-ANCA and MPO-ANCA. Initial renal histopathology of the 3 cases were consistent with ANCA-associated glomerulonephritis, which were classified into sclerosis, crescentic and mixed class respectively. After 8 months of treatments, repeated renal biopsy of case 3 had demonstrated progression to sclerosis class. Antithyroid drugs (PTU or MMI) were discontinued in 3 cases, and the children were all treated with corticosteroid combined with intravenous pulse cyclophosphamide therapy. Plasma exchange was performed in case 2 and case 3 due to rapidly progressive glomerulonephritis and disease recurrence (suspected pulmonary hemorrhage), respectively. Case 3 was treated with rituximab combined with mycophenolate mofetil after recurrence. The extrarenal symptoms relieved quickly after treatments in all cases. P-ANCA and MPO-ANCA became negative in case 1 and case 2 after 6 months of treatments but they were persistently positive in case 3. Three cases were followed up for 24 months, 10 months and 12 months, respectively: case 1 develop chronic kidney disease (CKD) stage 2 with normal urinalysis; case 2 develop CKD stage 5 and had sudden death at home at 10-month follow-up; case 3 develop CKD stage 4 with nephrotic proteinuria and microscopic hematuria. (2) There were totally 30 pediatric cases with AAV induced by PTU and MMI, including 27 reported cases in the literature and 3 cases in this study. Symptoms of AAV appeared in children after an average administration of (37.5±4.0) months of PTU (range from one month to 96 months and 8 months of MMI alone). Kidney (28 cases, 93.3%) and lung (12 cases, 40.0%) were commonly involved, while brain (2 cases, 6.7%) was rarely involved. The pathological changes of kidney were crescent nephritis (5/23) and necrotizing pauci-immune complex nephritis (11/23). The total remission rate was 93.3% (28/30) after antithyroid drugs withdrawal and treatment with corticosteroids and immunosuppressive therapy, however, there were still severe cases with progression to CKD stage 5, and death. (3) Thirty cases were divided into complete response group ( n=19) and incomplete response group ( n=11) according to the treatment response. Compared with complete response group, the proportions of massive proteinuria (8/11 vs 5/19), fibrinoid necrosis (7/9 vs 4/14), deposition of immune complex in renal tissues (6/9 vs 2/14) and administration of immunosuppressants (10/11 vs 5/19), and degree of tubular atrophy (0/1/2/3 grade, 2/4/2/1 vs 9/5/0/0) in incomplete response group were higher (all P<0.05). Conclusions:PTU and MMI can both induce AAV in children, and AAV may occur after short-term course of administration. Kidney and lung are commonly involved while brain involvement is rarely seen. Timely withdrawal of antithyroid drugs and proper treatments with corticosteroids and immunosuppressants can result in high remission rate, though there are still some severe cases. Nephrotic-range proteinuria, renal fibrinoid necrosis, immune-complex deposition and tubular atrophy may be the risk factors of AAV for poor prognosis.
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Objective:To explore the efficacy and safety of Rasburicase therapy in critically ill children su-ffering from advanced Burkitt′s lymphoma.Methods:A retrospective analysis of children with advanced Burkitt′s lymphoma was admitted to Pediatric Intensive Care Unit, the First Affiliated Hospital of Sun Yat-Sen University, from January 2015 to May 2020 and accepted treatment.According to the uric acid-lowering therapies, patients were divided into 2 groups, namely Rasburicase group (Group R) and traditional treatment group (Group T), to compare the effects of hypouricemic treatment and the prognosis between the 2 groups.Results:Twenty-nine children with advanced Burkitt′s lymphoma were included in this study, with 13 cases (44.83%) of stage Ⅲ and 16 cases (55.17%) of stage Ⅳ.Abdominal mass/ abdominal distension (13 cases, 44.83%) and abdominal pain (7 cases, 24.14%) were the main reasons of initial medical visit attendance.The most common primary tumor site was abdominal/ pelvic cavity (21 cases, 72.41%), followed by head or neck (6 cases, 20.69%). There were 15 cases in Group R and 14 cases in group T. No significant differences in serum creatinine, lactate dehydrogenase and uric acid were detected between the 2 groups (all P>0.05). The proportion of serum uric acid recovery rate of 24 hours and 72 hours after initial treatment in Group R were significantly higher than those in T group (85.71% vs.25.00%, 100.00% vs.25.00%, all P<0.01). Although there were no obvious differences in the incidence of tumor lysis syndrome between the 2 groups (33.33% vs.64.29%, P=0.096), the incidence of acute renal injury, renal replacement therapy requirement, serious complications and the 28 day mortality in Group R were remarkably lower than those in Group T (33.33% vs.85.71%, 13.33% vs.64.29%, 20.00% vs.78.57%, 0 vs.35.71%, all P< 0.05). Conclusions:Rasburicase can effectively reduce the serum uric acid level and decrease the incidence of acute kidney injury and other severe complications, thus improving the prognosis of children experiencing advanced Burkitt′s lymphoma.
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Objective:To investigate the impact of different type of dyslipidemia on clinical and pathological characteristics in children with IgA nephropathy (IgAN).Methods:A retrospective study was performed at the Children Kidney Disease Center, the First Affiliated Hospital of Sun Yat-sen University between January 2006 to September 2019. Children diagnosed with primary IgAN was divided into dyslipidemia group and normal blood lipid group according to whether the blood lipid is normal, and was divided into the following four groups: hypercholesterolemia group, hypertriglyceridemia group, mixed hyperlipidemia group and low high-density lipoprotein cholesterol (HDL-C) group according to clinical classification. The clinical and pathological features in different groups were analyzed, and the risk factors of dyslipidemia were analyzed by using multivariate logistic regression analysis.Results:A total of 252 children with IgAN were enrolled in this study, including 169 males and 83 females, with a male/female ratio of 2.04∶1 and an age of (9.3±3.1) years. Among them, 34.5% IgAN children were complicated with hypertension, and 170 cases (67.5%) were in dyslipidemia group, 82 cases (32.5%) in normal blood lipid group. According to clinical classification, the children in dyslipidemia group were divided into hypercholesterolemia group (58 cases, 23.0%), hypertriglyceridemia group (16 cases, 6.3%), mixed hyperlipidemia group (77 cases, 30.6%) and low HDL-C group (19 cases, 7.5%). The systolic blood pressure, diastolic blood pressure, proportion of hypertension, blood urea nitrogen, uric acid and urinary protein in dyslipidemia group were higher than those in normal blood lipid group (all P<0.05), and the levels of serum albumin, blood IgA and estimated glomerular filtration rate (eGFR) were less (all P<0.05). The proportion of IgAN children in chronic kidney disease (CKD) stage 1 and CKD stage 2-5 with dyslipidemia was 65.0% and 84.4% respectively, and the proportion of IgAN children with CKD stage 2-5 in dyslipidemia group was higher than that in normal group ( P<0.05). The dyslipidemia group had a higher proportion of Lee Ⅲ-V grade than normal blood lipid group ( P<0.01). The results of Oxford pathological classification showed that the proportions of M1 and E1 in dyslipidemia group were higher than those in normal lipid group (all P<0.05), and there was no significant difference in segmental glomerulosclerosis, tubular atrophy or interstitial fibrosis and crescent between the two groups (all P>0.05). The comparison results between groups with different types of dyslipidemia showed that systolic blood pressure, diastolic blood pressure, serum uric acid and urinary protein in the mixed hyperlipidemia group were higher than those in other groups (all P<0.05), and the serum albumin level was less ( P<0.01). The results of Oxford pathological classification showed that the proportion of E1 in hypercholesterolemia group and mixed hyperlipidemia group was higher ( P<0.05). Multivariate logistic regression analysis showed that hypertension ( OR=2.734, 95% CI 1.327-5.632, P=0.006) and low serum albumin ( OR=0.838, 95% CI 0.791-0.889, P<0.001) were the risk factors of dyslipidemia in children with IgAN. Conclusions:In our center, 67.5% IgAN children are accompanied by dyslipidemia. The clinical manifestations and pathological changes of these dyslipidemia children are more severe than those with normal blood lipid, and the IgAN children with mixed hyperlipidemia are more notable. Hypertension and low serum albumin are the risk factors of dyslipidemia in children with IgAN.
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Objective:To explore the diagnosis and treatment of focal segmental glomerulosclerosis (FSGS) post-kidney transplantation in children.Methods:Clinical data were retrospectively analyzed for 6 FSGS children after transplantation from 2015 to 2019. Massive proteinuria (3.2-13 g/24 h) occurred at 4 days-49 days post-transplantation. For proteinuria, glucocorticoid plus therapeutic plasma exchange and/or rituximab were provided with supplemental ACEI/ARB drugs. Five cases received tacrolimus as maintenance therapy while another case had cyclosporin A as an initial intensive therapy and switched to tacrolimus.Results:Four cases achieved complete remission after therapy. One recipient showed partial remission. During a follow up period of 11 months to 4 years, serum creatinine remained normal and stable in five cases while one died from severe pulmonary infection.Conclusions:Once FSGS occurs post-transplantation, prompt treatment of pulse glucocorticoid plus therapeutic plasma exchange and/or rituximab with supplemental ACEI/ARB drugs may yield favorable outcomes.
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Anti-neutrophil cytoplasmic antibodies(ANCA)associated vasculitis(AAV)is a kind of necroti-zing vasculitis with oligomeric or non-immune complex deposits, mainly involving small to medium vessels, and multiple organs are also frequently involved.AAV in children remains rare.Renal involvement in children is more severe than that in adults.The severity of renal lesions and disease activity are important predictors of long-term outcomes of AAV in children.Newer immunosuppressive agents and plasma exchange have further improved the prognosis of AAV in recent years.Early diagnosis, accurate disease state evaluation, and the development of reasonable individualized treatment plans are of great clinical significance for improving the prognosis of children with AAV.In this paper, the pathogenesis, clinical manifestations, diagnosis and treatment of AAV in children were described in order to improve the level of diagnosis and treatment of AAV in children.
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Objective To analyze the relationship between the serum B-cell activating factor (BAFF) levels and clinical characters and pathological features in children with lupus nephritis (LN). Methods ELISA was used to detect the serum BAFF (sBAFF) levels of the 54 LN children diagnosed in the First Affiliated Hospital, Sun Yat-sen University during October 1, 2014 to December 31, 2016 and with complete clinical data. According to whether glucocorticoid or immunosuppressive agents has been used at their first admission, patients were divided into treated group (n=44) and non-therapy group (n=10). According to the renal response after induction treatment for 6 months, patients were divided into remission group (n=20) and non-response group (n=34). According to whether there was renal recurrence, they were divided into recurrence group (6 cases) and non-recurrence group (48 cases). According to renal biopsy, patients were divided into class-Ⅲ, class-Ⅳ and class-Ⅴ group. Another 15 healthy children were taken as a control group. The correlations between sBAFF and clinical manifestation, laboratory examination, renal biopsy and clinical outcome were analyzed. Results (1) Compared with the control group, the sBAFF was significantly increased in LN group (t=3.821, P<0.001). Compared with the non- neuropsychiatric systemic lupus erythematosus (NPSLE) group, sBAFF was significantly increased in NPSLE group (t=2.202, P=0.032). (2) Compared with that in treated group, sBAFF was significantly higher in untreated group (LSD - t=2.309, P=0.025). Compared with non-response group, sBAFF was significantly decreased in response group (LSD-t=2.035, P=0.046). (3) No significant difference was observed between class-Ⅲ, class-Ⅳ and class-Ⅴpathological classification group (F=1.080, P=0.459). sBAFF in LN children was not significantly correlated with the active index (AI) or chronic index (CI) of Austin index (r=-0.273, P=0.063; r=0.150, P=0.314). (4) In LN children, sBAFF has positive correlation with ESR and IgG level (r=0.289, P=0.036; r=0.340, P=0.017) and negative correlation with WBC (r=-0.337, P=0.013). Multiple linear regression model showed that serum IgG level (β'=0.517, P=0.001) and renal response (β'=-0.271, P=0.037) were independent influencing factors of sBAFF level. Conclusions Renal remission and serum IgG levels in LN children are influencing factors of sBAFF levels. sBAFF is helpful to clinical assessment on renal response of LN children.
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Objective To investigate the clinical, pathological features and risk factors of hyperuricemia in children with IgA nephropathy (IgAN). Methods A retrospective study of 269 primary IgAN children diagnosed between January 1, 2006 to December 31, 2017 at the Children Kidney Disease Center, the First Affiliated Hospital of Sun Yat-sen University, was performed in the hyperuricemia group (uric acid>350 μmol/L) and the normal uric acid group. The clinical and pathological characteristics were analyzed, and the risk factors of hyperuricemia were analyzed by using multivariate logistic regression analysis. Results There were 185 males and 84 females in the 269 IgAN children with age of (9.2 ± 3.1) years old, among whom there were 70 patients (26.0％) accompanied by hyperuricemia. Clinical indicators such as hypertension, urea nitrogen, serum creatinine, blood lipids, urinary protein in hyperuricemia group were higher than those in normal uric acid group (all P<0.05), while estimated glomerular filtration rate, serum total protein and albumin were less (all P<0.05). There were 58 patients (23.0％) and 12 patients (70.5％) associated with hyperuricemia among IgAN children with CKD 1-2 and CKD 3-5. The proportion of hyperuricemia in CKD stage 3-5 IgAN children was statistically higher than that in normal uric acid group (P<0.01). The hyperuricemia group had a higher proportion of Lee IV and V grade, and a lower proportion of the Lee III grade than the normal uric acid group (all P<0.05). According to the Oxford pathological classification score, there was no significant difference in total scores of renal lesions, glomerular score, and tubulointerstitial score between the two groups (all P>0.05). According to the Katafuchi semi-quantitative score, there was no significant difference in the total scores of renal lesions, glomeruli, and tubulointerstitial scores (all P>0.05), while the hyperuricemia group had higher renal vascular scores than the normal uric acid group (P<0.01). Multivariate logistic regression analysis showed that hypertension (OR=12.596, 95％CI 1.778-89.243, P=0.011), higher total cholesterol (OR=1.192, 95％CI 1.064-1.336, P=0.002), higher urea nitrogen (OR=1.273, 95％CI 1.104-1.468, P=0.001), proteinuria 3+(OR=1.875, 95％CI 1.309-2.684, P=0.001), proteinuria 4+(OR=1.627, 95％CI 1.241-2.134, P<0.001) and CKD stage 3 (OR=3.355, 95％CI 1.376-8.181, P=0.008) were the risk factors of hyperuricemia in children with IgAN. Conclusions Twenty-six percent IgAN children patients are accompanied by hyperuricemia, and their clinical parameters and pathological changes are more severe than those in normal uric acid group. Hypertension, higher total cholesterol, higher urea nitrogen, proteinuria 3+/4+and CKD stage 3 are the risk factors of hyperuricemia in children with IgAN.
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Objective To analyze the pathologic constitution,repeated renal biopsy,treatment,prognosis and focal segmental glomerulosclerosis (FSGS) risk factors of children with steroid-resistant nephrotic syndrome (SRNS).Methods A retrospective analysis was made of 172 SRNS cases of renal biopsy in the Pediatric Nephrology Center,the First Affiliated Hospital of Sun Yat-Sen University from September 1,2006 to August 31,2016.Results The main pathological types of 172 children with SRNS were FSGS in 72 cases (41.9％),minimal change disease (MCD) in 52 cases (30.2％),and mesangial proliferative glomerulonephritis (MsPGN) in 31 cases (18.0％).There were 11 cases (6.4％) with repeated renal biopsy,5 cases of 6 children with MCD changed to FSGS;3 cases of FSGS whose repeated renal biopsy were still FSGS,but the subtype had changed;2 cases of MsPGN changed to FSGS in repeated renal biopsy.Compared to non-FSGS,the age of onset of FSGS was smaller [3.0(1.7,6.0) years old vs.5.8 (3.4,8.9) years old],the plasma albumin of FSGS was lower [18.0 (14.0,22.9) g/L vs.20.0 (15.1,29.1) g/L],the 24 hours urine protein level was higher [136.0(76.0,200.0) mg/(kg · d) vs.93.0(55.3,150.0) mg/(kg · d)],and the differences were all significant(all P ＜ 0.05).Logistic regression analysis showed that the smaller the age(P =0.007),the higher the 24-hour urine protein(P =0.028),the greater the risk of FSGS.The receiver operating characteristic (ROC) curve analysis showed that the optimal critical value of 24 hour urine protein was 131 mg/(kg · d).The effective rate of Cycloposphamide (CTX) treatment in MCD children (10/12 cases) was higher than that of FSGS (1/5 cases) and MsPGN (1/2 cases),and the differences were statistically significant (all P ＜0.05).There was no significant difference in the curative effect of Tacrolimas (TAC) and Ciclosporin A (CsA) in children with FSGS,MCD and MsPGN (all P ＞ 0.05).In 62 cases of FSGS,25 cases (56.4％) were effective,and 37 cases (84.1％) were effective in 44 cases of MCD,15 cases (60.0％) were effective in 25 cases of MsPGN,and the difference of prognosis between different pathological types was statistically significant (P ＜ 0.05).Conclusions The most common pathological types of children with SRNS are FSGS,MCD,and MsPGN,but the pathological types can be converted to each other.The smaller the age is,the higher the 24-hour urine protein level is,and the greater the risk of FSGS of the pathological type.When the quantity of 24-hours urine protein was more than 131 mg/ (kg · d),it should be alert to the possibility of pathological type of FSGS.In children with MCD,the effective rate of CTX is higher than that of children with FSGS and MsPGN.The prognosis of FSGS is the worst but the prognosis of MCD is better.
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Gitelman syndrome(GS) is an autosomal recessive,salt-losing tubulopathy resulted from inactivating mutations in the SLCl2A3 gene that encodes the Thiazine diuretic sensitive sodium chloride cotransporter (NCCT).GS is characterized by hypokalemic metabolic alkalosis,hypomagnesemia and hypocalciuria.Diagnosis of GS is relied on the clinical symptoms,biochemical abnormalities and genetic test.All GS patients are suggested to keep high-sodium diet.Magnesium and potassium supplements are usually given to GS patients for lifelong to improve clinical symptoms.Individual management of GS includes health education,complication evaluation and regular follow-up with annual evaluation by a nephrologist.Cystinosis is a rare autosomal-recessive lysosomal storage disease caused by inactivating mutations in the CTNS gene that encodes the lysosomal cystine transporter,cystinosin,resulting in the accumulation of cystine within the lysosome.There are 3 clinical forms of cystinosis:infantile or early-onset nephropathic cystinosis,juvenile or late-onset nephropathic cystinosis and adult or ocular cystinosis.Diagnosis of cystinosis is based on the CTNS genetic test.Early diagnosis and early cystine-depleting therapy with cysteamine is essential to prevent or attenuate end-organ damage and improve overall prognosis.
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Objective To analyze the podocyte gene mutation in children with steroid -resistant nephrotic syndrome (SRNS),and to explore the clinical manifestations and prognosis of children with gene mutation,so as to pro-vide a theoretical basis for the diagnosis and treatment of SRNS gene mutation in children. Methods Twenty-four pa-tients with SRNS diagnosis and ages less than 14 years old were selected from the Pediatric Nephrology Center of First Affiliated Hospital of Sun Yat-Sen University during August 31,2014 to September 1,2016. The gene detection was performed through PCR amplification and second DNA general sequencing,in which the target genes were detected in 23 cases with nephrotic panel,and 1 case was sequenced with the exon gene. Results There were 14 cases of male and 10 cases of female in 24 cases of genetic testing. The median age of onset was 4. 7 years old. There were 9 cases of sim-ple type,15 cases of nephritis type. And all the cases were primary steroid-resistant. Within the 20 cases of renal biop-sy,there were 5 cases of minimal change disease (MCD),11 cases of focal segmental glomerulosclerosis(FSGS),and 4 cases of mesangial proliferative glomerulonephritis (MsPGN). In the 24 cases,there were 8 cases of gene mutation. Their age was (3. 97 ± 3. 61)years old. The ratio of male and female was 1. 67:1. 00. The main clinical classification was nephritis type (6/8 cases). The major genes were NPHS2(3 cases),NPHS1(2 cases),INF2(2 cases),MYO1E(1 case). And FSGS was the main pathological type (4 cases). Most of them were no remission or end stage renal disease (ESRD)(6/8 cases),including 2 cases of renal transplantation. The 24 hour urine protein level in the gene mutation group was significantly higher than that in the non-mutation group [195. 4 (166. 0,262. 4)mg/(kg·d)vs. 85. 4 (74. 5,101. 3 ) mg/(kg·d )],and the difference was statistically significant (Z ＝ -3. 674,P ＜ 0. 001 ). Conclusion The main mutation genes of children with SRNS were NPHS2,NPHS1 and so on. FSGS was the main pathological type. Most of them were no remission or ESRD. The higher of the 24 hour urine protein level,the more pos-sibility of genetic mutation.
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Objective@#To establish comprehensive laboratory reference intervals for Chinese children.@*Methods@#This was a cross-sectional multicenter study. From June 2013 to December 2014, eligible healthy children aged from 6-month to 17-year were enrolled from 20 medical centers with informed consent. They were assessed by physical examination, questionnaire survey and abdominal ultrasound for eligibility. Fasting blood samples were collected and delivered to central laboratory. Measurements of 15 clinical laboratory parameters were performed, including estradiol (E2), testosterone(T), luteinizing hormone(LH), follicle-stimulating hormone(FSH), alanine transaminase(ALT), serum creatinine(Scr), cystatin C, immunoglobulin A(IgA), immunoglobulin G(IgG), immunoglobulin M(IgM), complement (C3, C4), alkaline phosphatase(ALP), uric acid(UA) and creatine kinase(CK). Reference intervals were established according to central 95% confidence intervals for reference population, stratified by age and sex.@*Results@#In total, 2 259 children were enrolled. Finally, 1 648 children were eligible for this study, including 830 boys and 818 girls, at a mean age of 7.4 years. Age- and sex- specific reference intervals have been established for the parameters. Reference intervals of sex hormones increased gradually with age. Concentrations of ALT, cystatin C, ALP and CK were higher in children under 2 years old. Serum levels of sex hormones, creatinine, immunoglobin, CK, ALP and urea increased rapidly in adolescence, with significant sex difference. In addition, reference intervals were variable depending on assay methods. Concentrations of ALT detected by reagents with pyridoxal 5'-phosphate(PLP) were higher than those detected by reagents without PLP. Compared with enzymatic method, Jaffe assay always got higher results of serum creatinine, especially in children younger than 9 years old.@*Conclusion@#This study established age- and sex- specific reference intervals, for 15 clinical laboratory parameters based on defined healthy children.
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Objective To study the role of salvianolate in the treatment of inflammation of intestinal mucosa by colitis mice model.Methods A total of 60 C57BL/6J mice were divided into acute control group,acute model group,acute interventional group,chronic control group,chronic model group and chronic interventional group with 10 mice in each group.Dextran sodium sulfate (DSS) was used to establish the model.Meanwhile,the mice of interventional group received salvianolate peritoneal injection during modeling.The expression levels of NLR family pyrin domain containing 3 (NLRP3),apoptosis-assoeiated speck-like protein containing CARD (ACS) and cysteinyl aspartate specific proteinase 1 (caspase-1) were detected.And the absorbances of serum superoxide dismutase (SOD) and malonaldehyde (MDA) in mice serum were determined.Kruskal Wallis single factor analysis of variance,single factor analysis of variance,Student-Newman-Keuls (SNK) method and least-significant difference method were performed for statistical analysis.Results The expressions of NLRP3 at protein level of acute control group,acute model group,acute interventional group,chronic control group,chronic model group and chronic interventional group were 9 965.20 (196.81),16 703.38 (291.21),13 423.74 (209.28),10 112.01 (183.55),16 247.90 (505.44) and 12 674.95 (229.32),respectively.The expressions of NLRP3 of acute and chronic interventional group were both lower than those of acute and chronic model group,and the differences were statistically significant (both x2 =15.158,P＜0.01).The expressions of ACS at protein level were 9 744.09-±-546.58,16 555.44 ± 407.80,12 568.21±586.49,10066.32±435.63,14 911.73±384.51 and 13 751.37±322.30,respectively.The expressions of caspase-1 at protein level were 5 300.40±843.14,15 478.98± 174.09,10 587.46±821.60,5 517.28±876.16,13 164.01 ±416.47 and 8 856.27 ± 545.01,respectively.The expressions of ACS and caspase-1 of acute and chronic interventional groups were both lower than those of model groups,and the differences were statistically significant (F=260.56,329.36,240.38 and 236.26,all P＜0.01).The serum levels of SOD were (282.08±28.24),(221.87±5.81),(231.45±1.84),(267.08±43.63),(237.09±34.09) and (257.78 ± 4.68) U/mL,respectively.There was no significant difference between acute model group and acute interventional group (P＞0.05).SOD level of chronic interventional group was higher than that of model group,and the difference was statistically significant (t=-2.65,P =0.021).The serum levels of MDAwere (1.31±0.40),(6.95±1.57),(2.98±1.41),(1.21±0.16),(9.38±3.73)and (3.74±0.81) nmol/L,respectively.MDA levels of acute and chronic interventional groups were lower than those of acute and chronic model groups,and the differences were statistically significant (t=4.88 and 4.02,both P＜0.01).Conclusion Salvianolate may alleviate oxidative stress response by adjusting the activity of NLRP3 inflammasome which takes part in reducing intestinal inflammation.
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Objective To study the role of salvianolate in the treatment of inflammation of intestinal mucosa by colitis mice model.Methods A total of 60 C57BL/6J mice were divided into acute control group,acute model group,acute interventional group,chronic control group,chronic model group and chronic interventional group with 10 mice in each group.Dextran sodium sulfate (DSS) was used to establish the model.Meanwhile,the mice of interventional group received salvianolate peritoneal injection during modeling.The expression levels of NLR family pyrin domain containing 3 (NLRP3),apoptosis-assoeiated speck-like protein containing CARD (ACS) and cysteinyl aspartate specific proteinase 1 (caspase-1) were detected.And the absorbances of serum superoxide dismutase (SOD) and malonaldehyde (MDA) in mice serum were determined.Kruskal Wallis single factor analysis of variance,single factor analysis of variance,Student-Newman-Keuls (SNK) method and least-significant difference method were performed for statistical analysis.Results The expressions of NLRP3 at protein level of acute control group,acute model group,acute interventional group,chronic control group,chronic model group and chronic interventional group were 9 965.20 (196.81),16 703.38 (291.21),13 423.74 (209.28),10 112.01 (183.55),16 247.90 (505.44) and 12 674.95 (229.32),respectively.The expressions of NLRP3 of acute and chronic interventional group were both lower than those of acute and chronic model group,and the differences were statistically significant (both x2 =15.158,P＜0.01).The expressions of ACS at protein level were 9 744.09-±-546.58,16 555.44 ± 407.80,12 568.21±586.49,10066.32±435.63,14 911.73±384.51 and 13 751.37±322.30,respectively.The expressions of caspase-1 at protein level were 5 300.40±843.14,15 478.98± 174.09,10 587.46±821.60,5 517.28±876.16,13 164.01 ±416.47 and 8 856.27 ± 545.01,respectively.The expressions of ACS and caspase-1 of acute and chronic interventional groups were both lower than those of model groups,and the differences were statistically significant (F=260.56,329.36,240.38 and 236.26,all P＜0.01).The serum levels of SOD were (282.08±28.24),(221.87±5.81),(231.45±1.84),(267.08±43.63),(237.09±34.09) and (257.78 ± 4.68) U/mL,respectively.There was no significant difference between acute model group and acute interventional group (P＞0.05).SOD level of chronic interventional group was higher than that of model group,and the difference was statistically significant (t=-2.65,P =0.021).The serum levels of MDAwere (1.31±0.40),(6.95±1.57),(2.98±1.41),(1.21±0.16),(9.38±3.73)and (3.74±0.81) nmol/L,respectively.MDA levels of acute and chronic interventional groups were lower than those of acute and chronic model groups,and the differences were statistically significant (t=4.88 and 4.02,both P＜0.01).Conclusion Salvianolate may alleviate oxidative stress response by adjusting the activity of NLRP3 inflammasome which takes part in reducing intestinal inflammation.
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Objective To investigate the expression and effect of miR-22-3p in non-small cell lung cancer (NSCLC). Methods The miR-22-3p expression level in seventy-six NSCLC tissues and para-cancer tissues was detected by qRT-PCR. The relationship between the expression of miR-22-3p and gender,age,tumor size,histolo-gy grade,pathological type and lymph node metastasis was analyzed. The function of miR-22-3p on the prolifera-tion of NSCLC cells was tested by growth curve assay. Target genes of miR-22-3p were predicted by online software Targetscan. Luciferase reporter assay and qRT-PCR was used to certificate the prediction. Results The expression of miR-22-3p was increased in NSCLC tissues than the para-cancer tissues and was correlated to lymph node metas-tasis. Overexpression of miR-22-3p could suppress the proliferation of A549 cells. Astrocyte-Elevated Gene-1(AEG-1) was predicted to be a target of miR-22-3p. MiR-22-3p was revealed to bind to AEG-13′UTR by luciferase report-er assay. Overexpression of miR-22-3p could inhibit the expression of AEG-1 in A549 cells. Suppression of miR-22-3p could increase AEG-1 expression. Conclusion MiR-22-3p could inhibit the proliferation of NSCLC by tar-geting AEG-1.
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Objective To observe the effect of tiotropium combined Seretide in the treatment of elderly patients with moderate to severe COPD clinical curative effect and the influence on the quality of life of patients.Methods114 cases of moderate or severe COPD in our hospital from January 2014 to January 2016,were randomly divided into observation group and control group, 57 cases in each group.The control group was treated with Seretide treatment, the observation group were treated by tiotropium combined with Seretide treatment, compared two groups of patients with curative effect and quality of life.ResultsBefore treatment, there were no significant differences in lung function index, MRC score, 6MWT and WHOQOL-100 scores between the two groups;After treatment, FEV1/FVC and FEV1% in the observation group were significantly higher than in the control group, and the difference was statistically significant (P<0.05);the dyspnea severity score (MRC) and six minute walk test (6MWT) in the observation group were significantly better than those in the control group, and the differences were statistically significant (P<0.05);the quality of life score (WHOQOL-100) in the observation group was significantly higher than in the control group, the difference was statistically significant (P<0.05).ConclusionTiotropium bromide combined with nimesulide in the treatment of elderly patients with moderate or severe COPD is effective, and can effectively improve the level of pulmonary function, improve the quality of life of patients.
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Objective To investigate the therapeutic effect of ambroxol hydrochloride on severe pneumonia, and the influence on the inflammatory cytokines of TNF-alpha and hs-CRP etc.MethodsThe clinical data of 70 patients with severe pneumonia patients treated in our hospital from December 2014 to August 2016 were retrospectively analyzed.The patients were divided into control group(n=30) and observation group(n=40) according to the treatment methods, the control group was given routine treatment, the observation group was given ambroxol hydrochloride on the basis of conventional treatment.The therapeutic effect of the two groups was observed, the differences of serum levels of inflammatory cytokines, pulmonary function, cough and expectoration symptom scores of the two groups were compared before and after treatment.ResultsThe effective rate of the observation group was 97.50%, which was significantly higher than that of the control group(80.00%);There was no significant difference in serum inflammatory cytokine levels between the two groups before treatment, after treatment,the levels of IL-6, IL-8, hs-CRP and TNF-alpha the observation group were lower than those in the control group;There was no significant difference in the indexes of lung function between the two groups before treatment.After treatment, the levels of FVC, FEV1 and FEV1/FVC in the observation group were higher than those in the control group;There was no significant difference in symptom score between the two groups before treatment.After treatment, cough, sputum volume, cough ease and wheezing scores in the observation group were lower than in the control group.ConclusionAmbroxol hydrochloride has a good therapeutic effect on severe pneumonia,which can significantly reduce the levels of inflammatory cytokines such as TNF-α and hs-CRP, and improve the related symptoms, and has good application value.
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Objective To explore the significance of detecting miR-145 hypermethylation in non-small cell lung cancer (NSCLC). Methods Seventy-five NSCLC tissues and adjacent tissues was collected from May 2012 to January 2015. The methylation status of miR-145 promoter was tested by bisulfite sequencing PCR (BSP) and the expression of miR-145 evaluated by ISH. The correlation between miR-145 methylation and clinical parameters , and the relationship between miR-145 methylation and expression were statistically analyzed. Results The hypermethy-lation ratio of miR-145 in NSCLC tissues was higher than that in the adjacent tissues. Hypermethylation of miR-145 was correlated with NSCLC differentiation stage, but not with gender and age. In NSCLC, miR-145 hypermethyla-tion was negatively related with its expression. Conclusion MiR-145 hypermethylation is closely related with dif-ferentiation stage in NSCLC tissues. MiR-145 hypermethylation may be a potential biomarker for estimating NSCLC differentiation stage.
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ObjectivesTo investigate the composition of clinical classiifcation and pathological patterns and their rela-tionships and change in children with renal disease undergoing biopsy.MethodsA retrospective analysis of pathological and clinical data obtained from children (≤14 year) with renal disease undergoing biopsy from 1984-1997 and from 1998-2011 was performed.ResultsOne thousand four hundred and sixty-two children underwent renal biopsy in 28 years, and 1313 patients were recruited in this study, 824 males (62.8%) and 489 females (37.2%). The mean age was 9 years and 4 months at renal biopsy. There were 921 children (70.1%) with primary glomerular disease (PGD) and 312 children (23.8%) with secondary glomerular disease (SDG). The main clinical classiifcations of PGD were nephrotic syndrome (NS, 31.2%), isolated hematuria (IH, 16.1%), and acute glomerulonephritis (AGN, 11.0%). The main pathological patterns of PGD were IgA nephrop-athy (IgAN, 27.6%), minimal change disease (MCD, 24.0%), and mesangial proliferative glomerulonephritis (MsPGN, 16.9%). The main causes of SGD were lupus nephritis (LN, 40.7%), Henoch-Sch?nlein purpura nephritis (HSPN, 34.3%), and hepatitis B virus related glomerulonephritis (HBV-GN, 19.6%). In this 28 years, the composition of PGD was decreased, however, the compositions of SGD and other renal diseases were increased. Compared with 1984-1997, the pathological manifestations of IgAN, MCD and focal segmental glomeralosclerosis were increased, MsPGN, IgMN, and crescentic glomerulonephritis were decreased in 1998-2011. The difference was statistically significant (P<0.05). In SGD patients, HBV-GN was significantly decreased (P<0.05).ConclusionsPGD is the main disease in children undergoing renal biopsy. IgAN is the most common pathological pattern. NS is the most common clinical classiifcation. In this 28 years, the composition of PGD is decreased, SGD and other renal diseases are increased in children undergoing renal biopsy.
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[Objective] To observe the effect of cyclosporine A (CSA) on the activity and expression of MMP-2 and MMP-9 in renal tubular epithelial cells. [Methods] NRK52E cells were cultured until its reached confluent. Then NRK52E cells were exposed to different concentration of CSA (0, 0.42, 0.84, 4.2, and 8.4 μmoL/L) for 48 h or 72 h respectively. MMP-2 and MMP-9 activities were detected by gelatin zymography. The expression of MMP-2 and MMP-9 mRNA were detected by RT-PCR. [Results] MMP-2 activity and mRNA levels were decreased in a dose dependent manner after exposed to different concentration of CSA for 48 h or 72 h in NRK52E cells. Compared with control (CSA 0 μmoL/L), CSA 0.42, 0.84, 4.2, 8.4 μmoL/L decreased the MMP-2 activities to 27%, 24%, 11%, and 9% respectively; The differences are significant, P<0.05. But the MMP-9 activity and mRNA levels were increased after exposed to CSA for 48 h or 72 h in NRK52E cells. Compared with control group, CSA 4.2 μmoL/L exposure increased MMP-9 activity to 438% in 48 h, and 237% in 72 h; the differences are significant as well, P<0.05. [Conclusion] A dose-dependent decrease in the expression and activity of MMP-2, and the up-regulation of the expression and activity of MMP-9 by CSA in renal epithelial cells may related to CSA associated tubulointerstitial damage.