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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.
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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.
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It is critical to regulate the senescence-associated secretory phenotype (SASP) due to its effect on promoting malignant phenotypes and limiting the efficiency of cancer therapy. In this study, we demonstrated that marchantin M (Mar-M, a naturally occurring bisbibenzyl) suppressed pro-inflammatory SASP components which were elevated in chemotherapy-resistant cells. Mar-M treatment attenuated the pro-tumorigenic effects of SASP and enhanced survival in drug-resistant mouse models. No toxicity was detected on normal fibroblast cells or in animals following this treatment. Inactivation of transcription factor EB (TFEB) and nuclear factor-B (NF-B) by Mar-M significantly accounted for its suppression on the components of SASP. Furthermore, inhibition of SASP by Mar-M contributed to a synergistic effect during co-treatment with doxorubicin to lower toxicity and enhance antitumor efficacy. Thus, chemotherapy-driven pro-inflammatory activity, seen to contribute to drug-resistance, is an important target for Mar-M. By decreasing SASP, Mar-M may be a potential approach to overcome tumor malignancy.
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Cystic fibrosis (CF) is a fatal autosomal-recessive disease caused by mutations in the CF transmembrane conductance regulator (CFTR) gene. CF is characterized by recurrent pulmonary infection with obstructive pulmonary disease. CF is common in the Caucasian population but is rare in the Chinese population. The symptoms of early-stage CF are often untypical and may sometimes manifest as Bartter syndrome (BS)-like hypokalemic alkalosis. Therefore, the ability of doctors to differentiate CF from BS-like hypokalemic alkalosis in Chinese infants is a great challenge in the timely and accurate diagnosis of CF. In China, sporadic CF has not been diagnosed in children younger than three years of age to date. Three infants, who were initially admitted to our hospital over the period of June 2013 to September 2014 with BS-like hypokalemic alkalosis, were diagnosed with CF through exome sequencing and sweat chloride measurement. The compound heterozygous mutations of the CFTR gene were detected in two infants, and a homozygous missense mutation was found in one infant. Among the six identified mutations, two are novel point mutations (c.1526G > C and c.3062C > T) that are possibly pathogenic. The three infants are the youngest Chinese patients to have been diagnosed with sporadic CF at a very early stage. Follow-up examination showed that all of the cases remained symptom-free after early intervention, indicating the potential benefit of very early diagnosis and timely intervention in children with CF. Our results demonstrate the necessity of distinguishing CF from BS in Chinese infants with hypokalemic alkalosis and the significant diagnostic value of powerful exome sequencing for rare genetic diseases. Furthermore, our findings expand the CFTR mutation spectrum associated with CF.
Subject(s)
Female , Humans , Infant , Male , Alkalosis , Bartter Syndrome , China , Cystic Fibrosis , Diagnosis , Genetics , Cystic Fibrosis Transmembrane Conductance Regulator , Genetics , Diagnosis, Differential , Exome , Hypokalemia , MutationABSTRACT
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.
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AIM: To observe the effect of exogenous androgen responsive element decoy on the promoter of prostate specific antigen (PSA) and the growth of LNCaP cells for searching the possibility of gene therapy for prostate cancer. METHODS: Firstly, pGL3 - PSA luciferase expression vector containing 640bp - promoter fragment of PSA gene was constructed. Then, a 23 -mer phosphorothioated ARE decoy based on the deduced ARE sequence at the promoter region of PSA gene was synthesized. pGL3 - PSA and ARE decoy DNA were cotransfected into PC3 - M cell by lipofectamineTM 2000. Through detecting the activity of luciferase, the effect of ARE decoy on the promoter of PSA was studied. Then the ARE decoy DNA was transfected into LNCaP cells. The effect of decoy DNA on the proliferation of LNCaP cells was examined by using MTT assay. The effects of apoptosis were detected by phase contrast microscopy, DNA agrose gel electrophoresis and flow cytometry. Meanwhile, the nuclear extract was prepared from LNCaP cells and DNA - protein interactions were examined by electrophoretic mobility shift assay (EMSA). RESULTS: The reporter assay showed that the aetivity of luciferase was significantly reduced in the ARE decoy - transfected cells, bnt not in the cells transfected with the control decoy. EMSA demonstrated specific binding of the ARE decoy to androgen receptor. The growth of LNCaP was remarkably inhibited and apoptotic morphological changes as well as DNA fragmentation were observed in the ARE decoy- transfected cells. The rate of apoptosis was 22.4% detected by FCM. CONCLUSION: The ARE decoy is capable of inhibiting the promoter of PSA gene and inducing the apoptosis in prostate cancer cells. It may become a potential therapeutic tool for prostate cancers.