AIM: To establish a model of staphylococcal enterotoxin B (SEB)-induced steroid resistance in human peripheral blood mononuclear cells (PBMCs), and to investigate the potential mechanism of SEB superantigen-induced steroid resistance in vitro. METHODS: PBMCs were isolated from normal children blood by Ficoll-Hypaque gradient centrifugation and stimulated with SEB at different concentrations. The proliferation rate of cells was measured by MTT assay. The subcellular localization of glucocorticoid receptor α (GRα) was examined by confocal microscopy. Protein phosphorylation was measured by means of Western blotting. RESULTS: SEB induced steroid resistance in a range of 10-500 μg/L and no significant difference among concentrations was observed. In SEB-stimulated PBMCs, the GRα did not translocate to the nuclear after dexamethasone treatment. ERK inhibitor U0126 significantly attenuated the inhibition of GRα nuclear translocation in SEB-stimulated PBMCs. SEB also induced more rapid and sustained phosphorylation of ERK1/2 in PBMCs. CONCLUSION: This study demonstrates that SEB may contribute to steroid resistance through ERK pathway and is associated with abrogation of GRα nuclear translocation.

10.3969/j.issn.1000-3606.2013.06.020

Objective To analyze the clinical and pathological characteristics of Alport syndrome in children. Methods Clinical and pathological information gathered from 62 patients during March 1989 to August 2012 was retrospectively analyzed. Results Four autosomal recessive Alport syndromes (AR-AS) and 58 X-linked Alport syndromes (XL-AS) were analyzed. Of the XL-AS, 47 were boys and 11 were girls. Most of patients induced by upper respiratory tract infections, and onset with hematuria and proteinuria. There was no signiifcant gender difference in family history, impaired renal tubular proteins, hypertension, im-paired renal function, hearing loss, ocular abnormalities or renal pathological changes under light microscopy. However, extensive lamination and split of glomerular basement membrane (GBM) dense layers were found in 83.0%male and 18.2%female patients (P=0.000) and the rest patients were presented with limited distribution of typical GBM changes. Proteinuria progressed signiif-cantly with age in XL-AS males (r=0.501, P=0.000). Five XL-AS patients developed to end stage renal disease (ESRD) between 11 to 16 years old. Conclusions XL-AS is the main inherited type and severe changes of GBM are common in XL-AS males. Proteinuria increases remarkably with age. The detection of type IV collagen in renal tissue or skin is helpful to diagnose Alport syndrome and conifrm inheritance modes.

To investigate the clinical efficacy of extended thymectomy by subxiphoid approach video-assisted thoracoscopic surgery(VATS) for myasthenia gravis. Methods We retrospectively analyzed the clinical date of 64 cases of myasthenia gravis treated by subxiphoid approach VATS in the same surgical team from September 2015 to April 2018. The patients were equally divided into 4 groups(A, B, C and D) according to the date of operation. Comparisons were made among the four groups in operation time, blood loss during operation, rate of conversion to thoracotomy, postoperative complications, postoperative hospital stay, duration and amount of postoperative chest tube drainage, frequenlly of surgery. The operative effect of different stage was analyzed. Results There were no intraoperative deaths. 1 patient(group A) was converted to thoracotomy. 3 patients(2 cases of group A; 1 case of group D) had lung infection. 1 patient(group B) developed myasthenia crisis after surgery, and the rest patients showed obvious improvement in postoperative myasthenia symptoms. No significant differences were found in postoperative complications, rate of conversion to thoracotomy, postoperative hospital stay, duration and amount of postoperative chest tube drainage among the 4 groups(P >0. 05). The operation time was significantly longer in group A(186. 25 ± 25. 79) min than the other 3 groups [B(128. 75 ± 16. 28) min, C(135. 00 ± 21. 29) min, D(128. 75 ± 19. 62)min], P <0. 05. The blood loss in surgery was significsntly more in group A(110. 00 ±38. 82)ml than that in the other 3 groups[B(63. 75 ±28. 26)ml, C(58. 13 ±27. 86)ml, D(58. 75 ±25. 00)ml], P <0. 05, while no statistical difference was found among group B, C and D. The frequency of surgery was increased from 1. 6 cases in group A to 2. 3, 2. 7 and 2. 7 cases one month in B, C and D, respectively. Conclusion The results of the present study have shown that subxiphoid approach VATS thymectomy is safe and feasible for the treatment of MG patients. For thoracic surgeons with certain experience in thoracoscopic technique, a plateau of the surgical skill of the subxiphoid opproach can be reached after learning curve procedures.

Objective:To report two cases of steroid-resistant nephrotic syndrome (SRNS) caused by LAMB2 gene mutation, and summarize the characteristics of genotype, clinical and pathological phenotypes of children with LAMB2 gene mutation. Methods:Two cases with SRNS caused by LAMB2 gene mutation were from Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology in December 2013 and September 2019. The demographic, family history and clinical data of two cases were collected, and the peripheral blood genomic DNA was captured and sequenced by whole exome sequencing. PubMed, Medline, CNKI and Wanfang databases were searched to summarize the clinicopathological phenotypes and genotypes of patients with LAMB2 mutation. Results:Among the two cases with SRNS caused by LAMB2 gene mutation, the clinical phenotypes were all manifested as nephrotic level of proteinuria and hypoalbuminemia, and there was no extrarenal clinical manifestation. One case presented with basement membrane delamination and the other with focal segmental glomerulosclerosis (FSGS). LAMB2 mutations of two cases were Exon32 c.5390G>T(p.Cys1797Phe), Exon19 c.2557C>T(p.Arg853*) and Exon27 c.4370G>A(p.R1457Q), Exon23 c.3325G>A(p.E1109K), respectively. In literature retrieval, there were 37 cases with LAMB2 gene mutation, including 24 cases with renal biopsy data, 13 cases of focal segmental glomerulosclerosis (FSGS), 4 cases of minimal change disease, one case of diffuse mesangial sclerosis, one case of IgM nephropathy, two cases of thin basement membrane nephropathy, and three cases of mesangial hyperplasia. Among them, eight cases had basement membrane delamination tear. Among the 37 cases, 11 cases were homozygous, 22 cases were complex heterozygosity, and 4 cases were heterozygous mutation. Conclusions:LAMB2 mutation may cause delamination tear of glomerular basement membrane. The clinical phenotype is congenital nephrotic syndrome or SRNS. The literature review shows the extrarenal manifestations caused by LAMB2 mutation are mostly various ocular abnormalities, as well as respiratory, digestive and nervous system abnormalities, and the time of progression to end-stage renal disease is also different.

Objective:To determine a relationship between ultrasound shear wave elastography (SWE) and pathological lessions of renal tissues in children with chronic kidney disease (CKD).Methods:It was a cross-sectional observational study, involving children admitted to the Department of Pediatrics of Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology from January to December 2021 with definite pathological diagnosis through kidney biopsy. The SWE was used to determine the Young's modulus (elastic modulus) of the cortex and medulla of the upper, middle, and lower poles of the kidney. The renal histopathology was classified or graded. The statistical method was used to analyze the relationship between Young's modulus of the inferior polar cortex (YM cor) and medulla (YM med) of the right kidney and renal pathology. Results:The study included 110 children with definite pathological diagnosis through renal biopsy, aged (10.1±3.4) years old (2-17 years old), with 55 males (50.0%). The body mass index was (20.6±2.4) kg/m 2, and mean arterial pressure was (95±24) mmHg. There were 94 patients (85.4%) with CKD stage 1, 8 patients (7.3%) with CKD stage 2, and 8 patients (7.3%) with CKD stage 3. There was no significant difference of YM cor and YM med in the upper and middle poles of the right kidneys, and YM med in the lower poles of right kidneys in CKD patients with different stages (all P>0.05). Both YM cor [(15.75±3.36) kPa] and YM med [(13.50±2.43) kPa] of CKD stage 3 patients were significantly higher than those of CKD stage 1 patients [(12.94±2.45) kPa, (11.88±2.23) kPa](both P<0.05). There was no significant difference of YM cor and YM med in the lower poles of right kidneys between stage 1 and stage 2 CKD patients (both P>0.05). YM cor[(17.93±3.23) kPa] and YM med [(15.50±1.48) kPa] in patients with crescentic glomerulonephritis were higher than those in patients with focal segmental glomerulosclerosis [(12.71±2.42) kPa, (11.57±2.63) kPa] and mesangial proliferative glomerulonephritis [(12.73±2.04) kPa, (11.48±2.10) kPa](all P<0.05). There was no significant difference of YM cor and YM med between focal segmental glomerulosclerosis and mesangial proliferative glomerulonephritis (both P>0.05). YM cor [(16.30±2.63) kPa] and YM med [(15.54±1.59) kPa] of Lee's Ⅳ grade of IgA nephropathy were higher than those of Lee's Ⅲ grade [(13.32±2.70) kPa, (12.57±2.50) kPa](both P<0.05), while the International Study of Kidney Disease in Children grade of purpura nephritis had no significant correlation with YM cor and YM med (both P>0.05). YM cor [(15.41±2.37) kPa] and YM med [(13.82±2.59) kPa] of interstitial fibrosis/tubular atrophy (T1/T2) group of IgA nephropathy mixed with purpura nephritis were significantly higher than those of T0 group's [(12.99±2.40) kPa, (11.79±2.05) kPa] (both P<0.05). Moreover, crescent formation (C1) group had a higher YM cor [(14.21±2.77) kPa] and YM med [(12.80±2.47) kPa] than those in C0 group [(12.73±2.15) kPa, (11.59±1.97) kPa] (both P<0.05), while YM cor and YM med were unrelated to the mesangial hypercellularity (M), endocapillary cellularity (E), segmental sclerosis or adhesion (S) indicators (all P>0.05). In lupus nephritis patients, YM cor ( r=0.744, P=0.035) and YM med ( r=0.728, P=0.009) were favorably linked with the chronic index, but not with the activity index (both P>0.05). Conclusions:Renal interstitial fibrosis/tubular atrophy and crescentic development are connected with YM cor and YM med at the lower pole of the kidney as measured by SWE. SWE can be used to assess the chronic renal lesions in children with CKD in the early and middle stages. It may develop into a new noninvasive way to assess renal pathology.

Objective:To analyze the clinicopathological and gene mutation characteristics of children with autosomal dominant inheritance Alport syndrome (ADAS), and to improve the understanding of ADAS.Methods:Ten children with ADAS diagnosed in the Department of Pediatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology from September 2016 to February 2020 were enrolled.The clinicopathological and gene mutation features were retrospectively analyzed, and the patients were followed up.Results:(1) The median age at diagnosis was 5.7 (2.4, 9.8) years.Of 10 children, 6 cases (60.0%) showed a family history of renal failure, 4 cases (40.0%) presented with hematuria and proteinuria at diagnosis, and 2 cases (20.0%) suffered a high-frequency hearing loss.Renal biopsy showed extensive splitting and lamellation of the glomerular basement membrane (GBM) dense layer in 4 cases (40.0%), and segmental splitting and lamellation in 6 cases (60.0%). (2)Among 10 children, 4 cases (40.0%) were heterozygous mutations of COL4A3 gene, including 2 point mutations of glycine, and 2 splicing mutations.The other 6 cases (60.0%) were heterozygous mutations of COL4A4 gene, including collagen glycine point mutations in 4 cases, nonsense mutation in 1 case and large deletion in 1 case.Six mutations were new and never reported before. Conclusions:The early clinical presentations of children with ADAS are often atypical and extrarenal manifestations are less common.The GBM dense layer is mainly featured by segmental splitting and lamellation.Glycine point mutations account for the majority of the gene mutations.

To improve the understanding of clinicians on the diagnostic criteria and treatment principlis of pulmonary alveolar proteinosis(PAP),which is a rare respiratory disease.European Respiratory Society published the first edition guidelines for PAP,including a systematic review of the literature and the application of the grading of recommendations,assessment,development and evaluation(GRADE)approach to assess the certainty of evidence and the strength of recommendations.Five questions of patient,intervention,comparison,outcome(PICO)and two narrative questions were developed.Recommendations and evidence-based evidence were given,including management of PAP,whole lung lavage,granulocyte-macrophage colony-stimulating factor(GM-CSF)therapy,rituximab,plasma exchange,and lung transplantation.In addition,recommendations were given for the use of GM-CSF antibody testing,bronchoalveolar lavage,and lung biopsy.This study is to interpret the main content of the guideline.

Alport syndrome is a type of hereditary kidney disease caused by mutations in the type Ⅳ collagen gene.Depending on the genetic mode,it can be divided into X-linked Alport syndrome,autosomal dominant Alport syndrome,autosomal recessive Alport syndrome,and digenic Alport syndrome.The clinical manifestations are heterogeneous,ranging from isolated hematuria or hematuria with proteinuria to progressive renal failure,with or without extrarenal manifestations.This article reviews the genetic characteristics,biomarkers,and treatment-related research of Alport syndrome,aiming to provide reference for enhancing early diagnosis and treatment and optimize long-term prognosis.

Objective:To investigate the prognosis and risk factors of IgA vasculitis nephritis (IgAVN) in children.Methods:A retrospective cohort study was conducted. Clinical data were collected from 264 children who were pathologically diagnosed with IgAVN at Department of Pediatric Nephrology, Tongji Hospital, affiliated with Tongji Medical College, Huazhong University of Science and Technology, between January 2011 and December 2017. All patients had a follow-up period of more than 3 years. Clinical characteristics, renal pathology, 3-year and 5-year prognosis were analyzed. The patients were grouped based on gender, age of onset (≤6 years, >6-9 years, and >9 years), pathological classification (≤Ⅲ and>Ⅲ),whether the prognosis was complete remission at 3 and 5 years. Independent sample t-tests, ANOVA or chi-squared test were used for intergroup comparisons. Spearman correlation analysis was applied for ordinal data, and multivariate Logistic regression was used to analyze factors affecting the prognosis. Receiver operating characteristic (ROC) curve was utilized to evaluate the predictive value of these factors. Results:Of the 264 children with IgAVN, 153 were male and 111 were female, the age of onset was 8.3 (6.7, 10.3) years, 118 patients (45%) with onset age >6-9 years accounted for the highest proportion. All patients presented with skin purpura and renal involvement, primarily manifesting as hematuria and/or proteinuria. Microscopic hematuria was observed in 253 patients (95.8%), while 246 patients (93.2%) showed proteinuria. In 256 patients (97.0%), hematuria or proteinuria urinalysis was detected within 6 months of skin purpura onset, and 243 patients (92.0%) underwent renal biopsy within 6 months of renal involvement. The most common clinical subtype in 264 IgAVN children was hematuria and proteinuria (204 cases, 77.3%), with grade Ⅲ being the predominant pathological classification (181 cases, 68.6%). Among children ≤6 years old, the 3-year complete remission rate was higher in males than in females (83.9% (26/31) vs. 7/16, χ2=8.12, P=0.012). Factors independently associated with poor 5-year prognosis included time from hematuria or proteinuria urinalysis to renal biopsy >6 months, elevated serum cholesterol levels, and incomplete remission 3 years post-biopsy ( OR=5.41, 1.39, 6.02, 95% CI 1.40-20.86, 1.04-1.84, 2.61-13.88, all P<0.05). The serum cholesterol has a predictive value for 5-year prognosis ( P=0.020, AUC=0.62, 95% CI 0.52-0.71, Youden index=0.27, cutoff=4.37). Conclusions:For children with IgAVN aged≤6 years, the 3-year prognosis is better in males than in females. Time from hematuria or proteinuria urinalysis to renal biopsy >6 months, elevated serum cholesterol levels, and incomplete remission at 3 years post-biopsy may be independent risk factors for poor 5-year prognosis in children with IgAVN.