Objective:To analyze and summarize the clinical, genotypic and pathological characteristics of children with PAX2 gene mutation in China, and to provide information for the monitoring, treatment and prognosis of the disease. Methods:It was a case series analysis study. The clinical data of children with PAX2 gene mutation in Pediatric Nephrology Department, Tongji Hospital Affiliated to Tongji Medical College, Huazhong University of Science and Technology from January 2014 to December 2022 were collected, and peripheral blood gene DNA was extracted and sequenced for whole exome sequencing. The clinical, pathological and genotypic characteristics of PAX2 gene variation of children in China were summarized by searching PubMed, Medline, China National Knowledge Infrastructure and Wanfang database and compared with the cases in this single center. Results:Among the 13 children with PAX2 gene mutation, there were 9 males and 4 females, 12 patients with abnormal urine tests, 7 patients with small kidney volume by imaging examination, and 5 patients with renal cysts. The clinical phenotypes were congenital renal and urinary tract malformations in 8 cases, renal coloboma syndrome in 1 case, and hematuria or proteinuria in 3 cases. Five patients underwent renal biopsies, showing focal segmental glomerulosclerosis and C3 glomerulopathy in 1 case, focal segmental glomerulosclerosis in 1 case, thin basement membrane lesion in 1 case, and IgA nephropathy in 2 cases. The genetic testing in 13 children showed 9 de novo mutations and 4 new mutations of c.321G>A, c.213-8C>G, c.63C>A and c.449C>T. There were 2 cases of 76dupG (p.V26Gfs*28) mutant. A total of 51 Chinese children with PAX2 gene mutation were found in the literature search. There were 32 males and 19 females, 8 cases with small kidney volume and 12 cases with renal cysts. The clinical phenotypes were congenital anomalies of kidney and urinary tract in 28 cases, renal coloboma syndrome in 17 cases, and hematuria or proteinuria in 6 cases. Seven patients underwent renal biopsies, including 2 cases with focal segmental glomerulosclerosis, 1 case with minimal lesion, 1 case with mesangial proliferative glomerulonephritis, 1 case with IgA nephropathy, 1 case with membranous nephropathy and a case with focal proliferative sclerosing purpura nephritis combined with glomerular hypertrophy. Thirty-four cases were de novo mutations, and 12 mutations were from the father or mother. The father or mother of 5 children had no clinical manifestations, with normal renal function. There were 11 cases of 76dupG (p.V26Gfs*28) mutant. Conclusions:The clinical phenotypes and genotypes of PAX2 gene variation in Chinese children are diverse. The most common clinical phenotype of PAX2 gene variation is congenital anomalies of kidney and urinary tract. c.76dupG (p.V26Gfs*28) is the most common of PAX2 gene variant.

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.

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.

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 explore the clinical characteristics of one living-related kidney transplant recipient infected with 2019 coronavirus disease(COVID-19).Methods:The clinical diagnosis and treatment of one living-related kidney transplant recipient after the occurrence of COVID-19 were analyzed retrospectively. Course of onset, clinical manifestations, laboratory and image enamination, outpatient and inpatient therapies and outcomes.Results:The renal transplant recipient was diagnosed as COVID-19(severe) with influenza A virus infection based upon epidemiological survey, clinical manifestations, laboratory examinations, imaging findings and etiological tests. The clinical symptoms were gradually relieved and lung lesions became absorbed after tapering and withdrawing immunosuppressants, antiviral therapy of abidol/oseltamivir, antibiotic therapy, hormonal anti-inflammation, oxygen inhalation, nutritional supports and adequate rest.Conclusions:Living-related kidney transplant recipients have specific immunosuppressive states.The long-term effect of covid-19 on recipients should be determined through long-term follow-ups.

Objective: To analyze the clinical characteristics of one living-related kidney transplant recipient infected with 2019 coronavirus disease (COVID-19) . Method: The clinical diagnosis and treatment of one relative renal transplant recipient after the occurrence of COVID-19 were analyzed retrospectively, including the course of onset, clinical manifestations, blood routine test, renal function, lung CT scan, nucleic acid detection, outpatient and inpatient therapies and outcomes. Result: The case was diagnosed as COVID-19 (severe type) with influenza A virus infection. The clinical symptoms were gradually relieved and the lung lesions were absorbed through the treatment of reduce and stop taking immunosuppressant, antiviral therapy of abidol/oseltamivir, prevention of bacterial infection, hormone anti-inflammatory, oxygen inhalation, nutritional support and adequate rest. Conclusion This case present typical characteristics of COVID-19 in epidemiological investigation, clinical manifestation, examination, pulmonary imaging and etiology. After comprehensive treatment including reduce and stop immunosuppressive therapy, clinical cure was achieved. The long-term effect of COVID-19 on this immunosuppressive patient remains follow-up.

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.