Antithyroid drugs-induced antineutrophil cytoplasmic antibody-associated vasculitis in children: report of three cases and literature review / 中华肾脏病杂志

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.

The role of the NOD-like receptor thermal protein domain associated protein 3 inflammasome in children with antineutrophil cytoplasmic antibody-associated vasculitis / 中华实用儿科临床杂志

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.

Evaluation of Smart Dose's predictive effectiveness on vancomycin blood concentration / 药学实践杂志

Objective To evaluate clinical utility of the personalized drug delivery decision support system, Smart Dose, applied to the monitoring of therapeutic drugs in Chinese population. Methods Use Smart Dose system to predict the trough concentration of vancomycin in patients, analyze the difference between the predicted value and the measured value of the trough concentration, and to evaluate the prediction performance of the system for vancomycin blood concentration. Results Smart Dose adjusts the difference between the predicted value of concentration and the measured value, the average percentage error, and the average absolute percentage error is less than the difference between the predicted value of initial concentration and the measured value. The difference between the initial concentration prediction value and the measured value of the neurosurgery group was smaller than that of the non-neurosurgery group, and the prediction efficiency was better than that of the non-neurosurgery group. The predicted initial concentration of the high trough concentration group and the low-age group (<59 years old) are closer to the measured value. The predictive performance of different BMI for the initial concentration is similar. Conclusion Smart Dose system is more suitable for predicting the adjusted concentration of vancomycin; When used for initial concentration prediction, the prediction values of neurosurgery group, high trough concentration, and low age group are more accurate. Different BMI has similar performance in predicting initial concentration.

Diagnosis and treatment of focal segmentalglomerulosclerosis after kidney transplantation in children / 中华器官移植杂志

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.

Clinical and pathological features of different type of dyslipidemia in children with IgA nephropathy / 中华肾脏病杂志

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.

Advances in diagnosis and treatment of children with anti-neutrophil cytoplasmic antibodies - associated vasculitis / 中华实用儿科临床杂志

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.

Relationship between serum B-cell activating factor levels and clinicopathology in children with lupus nephritis / 中华肾脏病杂志

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.

Clinical and pathological features of hyperuricemia in children with IgA nephropathy at a single center / 中华肾脏病杂志

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.

Clinical analysis of gene mutation in children with steroid-resistant nephrotic syndrome in a single center / 中华实用儿科临床杂志

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.

Clinical analysis of renal biopsy in 172 cases with steroid-resistant nephrotic syndrome / 中华实用儿科临床杂志

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.

Resveratrol ameliorates cerebral ischemia/reperfusion injury by inhibiting endo-plasmic reticulum stress in rats / 中国免疫学杂志

Objective:To investigate the effect of resveratrol ( Res ) on endoplasmic reticulum stress induced by cerebral ischemia/reperfusion(I/R)injury in rats.Methods:The seventy-two male SD rats were divided randomly into three groups(n=20):sham operation group ( group S ) , I/R group and Res-treatment group ( group R ) .Focal cerebral I/R model was induced by electrocoagulation of left middle cerebral artery and occlusion of bilateral common carotid arteries followed by reperfusion after 30 min.The rats in Res group were treated with Res(50 mg/kg)i.p.7 d before the operation,once a day for 7 d.Neurological deficits were assessed at 24 h post-injury,followed by collecting the brain tissues.Cerebral infarct size was detected by TTC staining,and the water content of brain tissue were measured by wet-dry weight method.The expression of GRP78,p-PERK and CHOP proteins were deter-mined by immunohistochemistry and Western blot analysis.Results:Compared with sham group,the neurological deficit score and the brain water content were significantly increased(P<0.05),cerebral infarct size was enlarged(P<0.05),and the expression of GRP78, p-PERK and CHOP were up-regulated in I/R group(P<0.05).At the corresponding time,compared with I/R group,the neurological deficit score and the brain water content were markedly decreased(P<0.05),cerebral infarct size was smaller(P<0.05),the level of GRP78 was notablely increased(P<0.05),while the expression of p-PERK and CHOP were down-regulated in Res group(P<0.05). Conclusion:Resveratrol plays a protection role in ischemia-reperfusion injury, through inhibiting the endoplasmic reticulum stress in rats.

Research into the antibody detection technology of mink plasmacytosis and its current applications / 病毒学报

Mink plasmacytosis, caused by Aleutian Mink Disease Virus (AMDV), poses a threat to the development of the animal fur industry. Neutralizing antibodies against AMDV may result in a persistent infection rather than providing protection for minks. To date,no specific methods to prevent or cure this disease have been developed. In order to eliminate mink plasmacytosis, antibody detection technology has been used globally as a dominant approach to screen for AMDV-positive minks. This paper introduces the classical technology, counterimmunoelectrophoresis and emerging technology in terms of AMDV antibody detection,and provides a glimpse into the future development of these technologies.

Comparison of FACS analysis indicators and traditional infection indicators in early diagnosis of infection in premature infants / 国际检验医学杂志

Objective To compare the clinical application of FACS analysis indicators and traditional infection indicators in early diagnosis of infection in premature infants .Methods 60 premature infants were divided into the infected group (n=29) and non-in-fected group(n=31) according to their clinical symptoms and laboratory results .BD FACSCanto Flow Cytometry was employed to detect CD11b ,CD64 and CD45RO ,BACTEC 9120 Automated Blood Culture System was used to conduct body fluids and secretions culture .Sysmex XE-5000 Automated Hematology Analyzers and i-CHROMA Reader Immunofluorescence Analyzer were adopted to conduct the complete blood count test and hypersensitive C-reactive protein (hs-CRP) detection ,respectively .Receiver operator characteristic(ROC) curve was used to analyze the diagnostic value of indexes above in preterm infants with infection ,and their sen-sitivity ,specificity ,positive predictive value and negative predictive value were calculated .Results On the first day after birth ,neu-trophil CD11b ,CD64 ,monocyte CD64 and hs-CRP levels of preterm infants in infection group were obviously higher than those in non-infection group(P0 .05) .ROC area under the curve(AUC)>0 .7 was found in Neutrophil CD64 ,monocyte CD64 and hs-CRP ,which had higher value in early diagnosis of infection in premature infants .The highest sensitivity ,specificity ,positive pre-dictive value and negative predictive value were 79 .31% ,96 .78% ,83 .34% and 75 .00% ,respectively .Conclusion FACS analysis indicators has better clinical value in the early diagnosis of infection in premature infants .

Clinical analysis of prognostic factors in 118 children with acute kidney injury / 中华肾脏病杂志

Objective To explore the risk factors of prognosis for children with acute kidney injury (AKI). Methods Clinical data of 118 children with AKI, including the causes,clinical characteristics, laboratory features, renal pathological findings, treatment and outcome, were reviewed retrospectively. Association between risk factors and prognosis was analyzed. AKI was defined by the new classification criteria of the Acute Kidney Injury Network. Prognostic factors were determined by univariate methods and stepwise multiple logistic regression analysis. Results One hundred and eighteen patients (83 male, 35 female) were enrolled in the study, who admitted in our department between January 1, 2005 and May 31, 2008. Median age at the time of AKI children was 7.5 years (range 1 day-14 years), among whom 28.0% (33 cases) was less than 3.0years, 17.8% (21 cases) between 3.0 and 7.0 years and 54.2% (64 cases) more than 7.0 years.Patients' AKI was classified according to the staging system as follows: 52.5% stage 1, 32.2%stage 2 and 15.3% stage 3. The common causes of AKI children were infectious and autoimmune diseases (39.8%), renal vascular disease (27.1%) and circulatory disturbance (11.9%). Hospital mortality was 21.2%. Multivariate analysis showed that independent risk factors for death were need for mechanical ventilation (OR=51.75, P＜0.01＝, sepsis/septic shock (OR=14.76, P＜0.01＝, severe acidosis (OR=11.38, P＜0,01＝, and white blood cells (WBC) count more than 20.0×109/L (OR=8.51, P＜0.01＝. Conclusion Infectious and autoimmune diseases, renal vascular disease and circulatory disturbance are the common causes of AKI children. The important risk factors of death in AKI children are need for mechanical ventilation, sepsis/septic shock, severe acidosis, and WBC count more than 20.0×109/L.

Current situation, clinical characteristics and management of human swine influenza A H1N1) in children / 国际儿科学杂志

Human swine influenza A (H1N1) is a highly transmissible infectious disease, which has spreaded globally and represented a continuous pandemic threat. The novel virus has predominantly affected the children and young adults. Clinical manifestations generally appear mild, but there are still many patients with severe complications leading to hospitalization. According to the current reports, the mortality in the early stages of the pandemic appears no more than seasonal influenza A . Children (especially less than 5years) are considered to be at higher risk of infection and complications. Pediatric patients with a underlying significant chronic disease such as chronic respiratory disease,cardiovascular disease and immunodeficiency disease, are at a higher risk of death. The neuraminidase inhibitors Oseltamivir and Zanamivir are effective for prophylaxis and treatment. Effective vaccines are regarded to be crucial for the control of influenza pandemics. This review focuses on the epidemiological situation, clinical characteristics and management of human swine influenza A (H1N1), so as to provide practical advice for clinicians.

Expression and clinical significances o f CD62P and CD44 in the peripheral blood of children with lupus nephritis / 中华风湿病学杂志

Objective To study the levels of CD62P and CD44 in the peripheral blood of children with lupus nephritis (LN) and their clinical significances were investigated. Methods Twenty-two children with active LN were divided into two groups by their clinical features,nephritic syndrome group (NS group,12 patients) and nonnephritic syndrome group (non NS group, 10 patients). Those patients were also divided into two groups according to their pathologic grading,grade Ⅱ+Ⅲ group (6 patients) and grade Ⅳ+Ⅴ group(16 patients).According to their tubulointerstitial lesions (TIL), those patients were divided into three groups, TIL grade 0 group (5 patients), grade Ⅰ group (13 patients), grade Ⅱ group (4 patients). The blood of the 18 patients who were in inactive state after treatment were retested blood again. The levels of CD62P and CD44 in the peripheral blood were assayed by radioimmunoassay (RIA) and enzyme-linked immunoabsorbant assay (ELISA) in LN children and in 20 normal age and sex-matched controls, and their correlation with clinical peripheral blood levels of CD62P and CD44 in NS group, grade Ⅳ+Ⅴ group were significantly higher than CD44 were positively correlated with 24-hour proteinuria,ESR, urine NAG, urine β2-MG and the TIL grade (P<0.05 and P<0.01, respectively), but negatively correlated with the levels of serum complement 3 (C3) and albumin (ALB) (P<0.05).The levels of CD62P was positively correlated with those of CD44 (P<0.05). Conclusion CD62P and CD44 may be involved in the pathogenesis of LN. The peripheral blood levels of CD62P and CD44 in LN children could be used as one of the indicators for lupus activity, severity, treatment effectiveness and prediction of outcome.

Transcutaneous electrical nerve stimulation in treatment for symptomatic diabetic neuropathy: a systematic review of randomized controlled trials / 中华物理医学与康复杂志

Objective To systematically review the effectiveness and safety of transcutaneous electricalnerve stimulation (TENS) on symptomatic diabetic neuropathy (DNP). Methods Electronic databases such asPUBMED, EMBASE, Cochrane Central Register of Controlled Trials, and Chinese Biomedical Database weresearched by using such mesh and text keywords as "TENS" and "diabetic neuropathy". Randomized controlled trials(RCTs) on the effect of TENS on symptomatic diabetic neuropathy were included. Studies were selected and availa-ble data was extracted independently by two reviewers. Meta-analysis was performed using RevMan 4.2.8 software.Results Three RCTs involving 78 patients were included in this study. Compared with sham-stimulation, TENStherapy significantly reduced the score in pain (SMD -2.35, 95% CI [-4.24, -0.46 ] ) and the score in numb-ness (WMD -0.18, 95% CI [-0.32, -0.05 ] ). Subgroup analysis shows that TENS therapy was associated with a significant reduction in the score of pain in both 4-week treatment duration ( SMD - 5.37, 95% CI [ - 6.97,- 3.77 ] ) and 6-week treatment duration ( SMD - 1.01, 95% CI [ - 2.01, - 0.01 ] ), but not 12-week treatmentduration (SMD - 1.65, 95% CI [ -4.02, 0.73 ] ). Conclusion TENS therapy is a promising and safe strategyfor treatment of symptomatic diabetic neuropathy. More studies are still warranted to accumulate the evidence of theeffect of TENS therapy on DNP.