Screening of key genes in the pathogenesis of muscle atrophy in CKD-PEW children based on RNA sequencing.

BACKGROUND: In children with CKD, Protein Energy Wasting (PEW) is common, which affects the outcome of children and is an important cause of poor prognosis. We are aiming to explore the pathogenesis of muscle wasting in CKD-PEW children. METHODS: Blood samples of 32 children diagnosed with chronic kidney disease (CKD) and protein energy wasting (PEW) in our hospital from January 2016 to June 2021 were collected. RNA sequencing and bioinformatics analysis were performed. RESULTS: Based on GO (Gene Ontology) functional enrichment analysis, KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway enrichment analysis and differential gene expression analysis, a total of 25 CKD-PEW related genes were obtained including CRP, IL6, TNF, IL1B, CXCL8, IL12B, IL12A, IL18, IL1A, IL4, IL10, TGFB2, TGFB1, TGFB3, ADIPOQ, NAMPT, RETN, RETNLB, LEP, CD163, ICAM1, VCAM1, SELE, NF-κB1, NF-κB2. The most significantly differentially expressed gene was NF-κB2 (adjusted P = 2.81 × 10-16), and its expression was up-regulated by 3.92 times (corresponding log2FoldChange value was 1.979). Followed by RETN (adjusted P = 1.63 × 10-7), and its expression was up-regulated by 8.306 times (corresponding log2FoldChange value was 2.882). SELE gene were secondly significant (adjusted P = 5.81 × 10-7), and its expression was down-regulated by 22.05 times (corresponding log2FoldChange value was -4.696). CONCLUSIONS: A variety of inflammatory factors are involved in the pathogenesis of CKD-PEW in children, and chronic inflammation may lead to the development of muscle atrophy in CKD-PEW. It is suggested for the first time that NF-κB is a key gene in the pathogenesis of muscle wasting in CKD-PEW children, and its increased expression may play an important role in the pathogenesis of muscle wasting in children with CKD-PEW.

Attention to renal involvement: report of 17 Joubert syndrome cases in children of a single center in China.

BACKGROUND: Joubert Syndrome (JS) is a rare genetic developmental disorder. We are aiming for increasing awareness of this disease especially kidney involvement in children with JS. METHODS: Clinical and genetic data of 17 cases of JS in Beijing children's hospital in the past 21 years were collected retrospectively. RESULTS: Twelve males and 5 females, aged from 12d to 15y8m. The most common involvement was neurological system involvement. The second most common involvement was renal involvement: end stage kidney disease in 6 cases (35%), hematuria in 5 cases (29%), proteinuria in 5 cases (29%), renal diffuse lesions in 4 cases (24%), renal cystic lesions in 2 cases (12%), and echogenic enhancement of parenchyma in 2 cases (12%). 10 cases did genetic tests. 3 cases with renal deficiency all had RPGRIP1L gene mutation. CONCLUSIONS: The most common involvement of JS is neurological involvement, and the second is renal involvement. Pediatricians should improve awareness of JS and conduct systemic evaluation of children. More attention should be paid to renal involvement which may be onset hidden but fatal. Early recognition and diagnosis are the goals to delay the start to dialysis and improve quality of patients' life. The RPGRIP1L gene mutation maybe the most common gene mutation in JS and may have correlations with renal involvement.

Value of Oxford classification and ISKDC classification in the prognosis of children with Henoch-Schönlein purpura nephritis / 中华肾脏病杂志

Objective@#To analyze the Oxford classification (MESTC) and the International Study of Kidney Disease in Children (ISKDC) classification for evaluating the clinical manifestations, histological lesion and short-term prognosis of children with Henoch-Schönlein purpura nephritis (HSPN).@*Methods@#According to the Oxford classification and ISKDC classification, the histological lesions of children with HSPN diagnosed by renal biopsy from Beijing Children's Hospital affiliated to Capital Medical University from January 2018 to December 2018 were re-evaluated. The renal biopsy specimens of the selected subjects were scored according to the Oxford classification and the ISKDC classification. According to whether the first symptom was combined with renal performance, MESTC score and ISKDC classification, children were grouped. The differences in clinicopathological manifestations between the groups were compared. Correlation between MESTC and ISKDC grades was analyzed by nonparametric test rank correlation. Kaplan-Meier survival curve and Log-rank test were used to compare the difference of proteinuria remission rate between the two groups. Univariate and multivariate Cox regression equations were used to analyze the influencing factors of the proteinuria remission rate.@*Results@#A total of 78 children with HSPN were enrolled. There were 37 male patients (47.4%) with age of (10.4±2.9) years. When the patients were divided according to MESTC scores and ISKDC classification, the results showed that the proportion of children with nephrotic-range proteinuria in the group of endocapillary hypercellularity (E1, P=0.008), segmental glomerulosclerosis (S1, P=0.015) and ISKDCⅢ(P=0.041) was higher than that of E0, S0 and ISKDCⅡ groups. The proportion of children with E1 (P=0.015), crescents (C1&C2, P=0.025) or ISKDCⅢ(P=0.017) that had been treated with high-dose methylprednisolone was higher. The result of Kaplan-Meier survival curve showed more difficult for proteinuria remission in children with C2 are than C0&C1 group (P=0.026), while no difference were found when children were grouped by M, E, S, T and ISKDC. Multivariate Cox regression analysis showed that the C2 (HR=0.143, 95%CI 0.020-1.046, P=0.055) might be a risk factor for proteinuria remission, while the P value was close to 0.05.@*Conclusions@#Children with HSPN scored as ISKDCⅢ, E1 and S1 are more likely to show nephrotic-range proteinuria. C2 may indicate that patients are more difficult to achieve proteinuria remission.

Value of Oxford classification and ISKDC classification in the prognosis of children with Henoch-Sch(o)nlein purpura nephritis / 中华肾脏病杂志

Objective To analyze the Oxford classification (MESTC) and the International Study of Kidney Disease in Children (ISKDC) classification for evaluating the clinical manifestations,histological lesion and short-term prognosis of children with Henoch-Sch(o)nlein purpura nephritis (HSPN).Methods According to the Oxford classification and ISKDC classification,the histological lesions of children with HSPN diagnosed by renal biopsy from Beijing Children's Hospital affiliated to Capital Medical University from January 2018 to December 2018 were re-evaluated.The renal biopsy specimens of the selected subjects were scored according to the Oxford classification and the ISKDC classification.According to whether the first symptom was combined with renal performance,MESTC score and ISKDC classification,children were grouped.The differences in clinicopathological manifestations between the groups were compared.Correlation between MESTC and ISKDC grades was analyzed by nonparametric test rank correlation.Kaplan-Meier survival curve and Log-rank test were used to compare the difference of proteinuria remission rate between the two groups.Univariate and multivariate Cox regression equations were used to analyze the influencing factors of the proteinuria remission rate.Results A total of 78 children with HSPN were enrolled.There were 37 male patients (47.4％) with age of (10.4+2.9) years.When the patients were divided according to MESTC scores and ISKDC classification,the results showed that the proportion of children with nephrotic-range proteinuria in the group of endocapillary hypercellularity (E1,P=0.008),segmental glomerulosclerosis (S1,P=0.015) and ISKDC Ⅲ (P=0.041) was higher than that of E0,S0 and ISKDC Ⅱ groups.The proportion of children with E1 (P=0.015),crescents (C1&C2,P=0.025) or ISKDC Ⅲ (P=0.017) that had been treated with high-dose methylprednisolone was higher.The result of Kaplan-Meier survival curve showed more difficult for proteinuria remission in children with C2 are than C0&C1 group (P=0.026),while no difference were found when children were grouped by M,E,S,T and ISKDC.Multivariate Cox regression analysis showed that the C2 (HR=0.143,95％C1 0.020-1.046,P=0.055) might be a risk factor for proteinuria remission,while the P value was close to 0.05.Conclusions Children with HSPN scored as ISKDC Ⅲ,E1 and S1 are more likely to show nephrotic-range proteinuria.C2 may indicate that patients are more difficult to achieve proteinuria remission.

Predictive value of in vitro methyl thiazolyl tetrazolium assay chemosensitivity test of cytotoxic drug activity in breast cancer / 中国综合临床

Objective To investigate the value of methyl thiazolyl tetrazolium assay ( MTT) in predicting drug sensitivity of breast cancer cells in vitro. Methods From January 2010 to July 2016,one hundred and ninety-two patients with breast cancer who underwent modified radical mastectomy or breast conserving surgery (no preoperative radiotherapy or chemotherapy) in the Shanghai Fengxian District Central Hospital were selected. MTT method was used to determine the inhibitory level and sensitivity of 12 drugs and 3 chemotherapy regimens to primary cultured cancer cells of 192 patients with breast cancer. Results (1) The sensitivity of breast cancer cells to 12 drugs were in sequence from high to low as follows: Paclitaxel (PTX)＞ Epirubicin ( EPI )＞ Cisplatin ( DDP )＞ 5-Fluorouracil ( 5-FU )＞ Mitoxantrone ( MIT )＞Vincristine ( VCR )＞ Pirarubicin ( THP )＞ Isosophosphamide ( IFO )＞ Carboplatin ( CBP )＞Cyclophosphamide ( CTX)＞ Methotrexate ( MTX)＞ Changchun Rui bin ( NVB) . The sensitivity of chemotherapy regimens in the three groups from high to low was docetaxel/doxorubicin/cyclophosphamide (TAC )＞cyclophosphamide/epirubicin/fluorouracil ( CEF )＞cyclophosphamide/methotrexate/fluorouracil (CMF). The sensitivity rates of PTX,EPI and DDP were 54%(104/192),42%(81/192) and 37%(71/192) respectively. (2) The average inhibitory rates of DDP,CBP and MIT in stage III breast cancer was higher than those in stage I and II breast cancer,and the differences were statistically significant ( F＝11. 14,4. 303,3. 182,P＜0. 05). (3) HR-breast cancer is more sensitive than HR+breast cancer,PTX, EPI,THP,MIT in HER-2(+) breast cancer is more sensitive than in HER-2(－) breast cancer. Conclusion As a widely used drug sensitivity test method, MTT assay has a certain reference value for screening sensitive drugs and selecting clinical chemotherapy regimens in neoadjuvant chemotherapy of breast cancer. PTX,EPI and DDP are more sensitive to other breast cancer cells than other drugs. Chemotherapy based on in vitro susceptibility results improves the efficiency of chemotherapy and decreases the proportion of changes in chemotherapy schemes due to inefficiency.

Values of the integrated visual and auditory continuous performance test in diagnosing children with attention deficit hyperactivity disorder in clinic and school in China / 中华行为医学与脑科学杂志

Objective To explore the psychometric properties of the Chinese version of integrated visual and auditory continuous performance test (IVA-CPT) ,and to assess the diagnosis value of the Chinese version of IVA-CPT in two samples of children with attention deficit hyperactivity disorder (ADHD) in clinic and school.Methods 112 participants were divided into 4 groups:clinic group, clinic control group, school group and control group from school.The participants were measured by IVA-CPT and the results were compared.Results ①The integrated quotients of IVA-CPT had concordance with the dimensions of the DSM-ⅣV and ASRS.Each integrated quotients of IVA-CPT and each dimension of the DSM-ⅣV and ASRS were negatively correlated(school: r=-0.277, P＜0.05;clinic: r=-0.423, P＜0.05).The score of HI dimension was negatively correlated with integrated attention quotient and integrated inhibition quotient of IVA-CPT (r=-0.480, P＜0.01;r=-0.452, P＜0.01).② The results of the IVA-CPT and the comprehensive assessment had consistency for diagnosis of children with ADHD from the total subjects,the clinic ,and the school.And there were no difference between the sensitivity, the specificity, the coincidence rate, the missed diagnosis rate and the misdiagnosis rate of IVA-CPT when used to diagnose children with ADHD in clinic and school(x2=3.396, P＞0.05).③The IVA-CPT evaluation system had good stability according to the retest of a random sample of 25 subjects(P＜0.01).The pretest and posttest results of each full quotients of IVA-CPT were significantly correlated (P＜0.01).Conclusion The IVA-CPT not only can be used as auxiliary diagnostic tools to diagnose children with ADHD in clinic,it can be used as auxiliary diagnostic tools to diagnose children with ADHD in the community.

Analysis and follow-up of 28 children with methylmalonic acidemia combined with renal damage / 中华实用儿科临床杂志

Objective To understand the clinical characteristics, treatment effect and prognosis of children with methylmalonic acidemia (MMA) combined with renal damage, and to provide experiences about how to improve the level of diagnosis and treatment.Methods The medical records of children with MMA were collected from January of 2007 to December of 2013 in Beijing Children's Hospital Affiliated to Capital University of Medical Sciences,while the clinical manifestations,laboratory findings, imaging material, inspection results were analyzed, and the renal pathological gene analysis, treatment effect, and prognosis of MMA children with renal damage were studied, and follow-up was carried out for 3 months up to 7 years.Results Among the two hundred and ninety-six cases of MMA,28 cases (9.5％) with renal damage,including 19 boys and 9 girls, 18 patients with hyperhomocysteinemia.Their ages varied from 2 days to 13 years old when confirmed.The first symptoms of 16 cases were proteinuria, hematuria, and edema, 9 cases were complicated with acute renal failure,5 cases were diagnosed as hemolytic uremic syndrome,6 patients were diagnosed as nephrotic syndrome, receiving enough glucocorticoids treatment without improvement.The routine examination of the urine showed that proteinuria (241-3 060 mg/d), methylmalonic acid levels and urinary protein were positively correlated (r =0.982, P =0.003), as urinary β2-microglobulin [(360.386 ± 231.496) μg/L], retinol binding protein [(338.537 ± 243.293) μg/L] increased.Extrarenal clinical manifestations were the spiritual, mental and physical development retardations, seizures, anemia etc.Two cases had a positive family history.Renal pathology showed mesangial cells and mesangial matrix proliferation broadening, no electron dense deposits in mesangial area, renal tubular epithelial cell swelling degeneration, and immunofluorescence was negative.Gene analysis of 3 cases showed exon1:c.80A ＞ G,p.Q27R and exon1 :c.365A ＞ T,p.H122L/c.609 G ＞ A,p.W203X.Children with MMA were treated with vitamin B12 treatment.Two cases of multiple organ failure died during hospitalization, and 2 cases died after leaving hospital.After treatment, the level of urinary methylmalonic acid was significantly decreased, while nervous system symptoms improved significantly, and the mental state and the renal function were improved.Conclusions MMA may be associated with kidney damage,usually with severe renal tubular and glomerular impairment.Early diagnosis is the key,and timely treatment can effectively control the disease, improve the prognosis.

Progress of diagnosis and treatment for protein-energy wasting in children with chronic kidney disease / 中华实用儿科临床杂志

Protein-energy wasting is a common complication in patients with chronic kidney disease and also an independent risk factor for poor prognosis.The progress of diagnosis and treatment for protein-energy wasting in children with chronic kidney disease were summarized.

Clinical analysis of spontaneous bacterial peritonitis in children with nephrotic syndrome / 中华实用儿科临床杂志

Objective To explore the clinical feature of spontaneous bacterial peritonitis (SBP) in children with nephrotic syndrome (NS).Methods Eleven cases of SBP in children with NS from Department of Nephrology,Beijing Children's Hospital Affiliated to Capital University of Medical Science between January 2010 and June 2014 were analyzed retrospectively.The clinical features,laboratory data and efficacy of therapy were reviewed.Results In this study,12 episodes of primary peritonitis were detected in 11 patients.One patient had 2 attacks.There were 11 cases including 9 boys and 2 girls.The age of the patients ranged from 2 years and 11months to 14 years and 11 months.Nine cases of them received steroid therapy and/or cytotoxic drugs.Peritonitis was characterized by abdominal pain,mild abdominal pain occurred in 7 cases with slow onset.Ten cases had fever of varying degrees,8 cases had abdominal distention,5 cases had diarrhea and 4 cases had nausea and vomiting.Shock signs were present suddenly in 2 cases before therapy of antibiotics.Apparent edema and severe ascites were present in all cases.Five of them were presented with increasingly rapid severe ascites and showed no response to diuretic drugs.Blood investigation showed leukocytosis and high C-reactive protein.Serum albumin levels and IgG and CD4 ratio were very low in all cases.Ascites were like cloudy pus with raised neutrophil cells.Streptococcus pneumonia was positive in both blood culture and ascites culture in 2 cases.Cephalosporin was used empirically to all cases for 7 to 10 days in 9 cases and 4 weeks in 2 cases with positive blood culture.Paracentesis to release ascites fluid was performed in 5 cases with constant ascites.Eleven cases recovered from peritonitis completely.The proteinuria was negative in 2 cases after they recovered from peritonitis.Conclusions SBP was atypical in children with NS and sometimes patients might have to abdominal pain and rebound tenderness,which may be ignored and may induce deterioration suddenly and clinicians should be aware of it clearly.SBP could lead to relapse of NS and the cure of SBP by treatment could help the children recover from NS.

Protein-energy wasting in children with chronic kidney disease / 中华实用儿科临床杂志

Protein-energy wasting is a common complication in patients with chronic kidney disease and also an independent risk factor for poor prognosis.The pathogenesy and diagnosis of protein-energy wasting in children with chronic kidney disease,assessment of nutritional status were summarized.