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Objective To explore the phenotype-genotype correlation of Alport syndrome in children. Methods Retrospectively analyze the clinical and pathological features of 55 patients with Alport syndrome with COL4A mutations detected by second-generation sequencing, who were treated at Beijing Children's Hospital from January 2016 to December 2020. Results A total of 55 children with Alport syndrome were included. All cases had hematuria, including 31 cases (56.4%) with gross hematuria and 24 cases (43.6%) with microscopic hematuria. A total of 39 (70.9%) patients also had proteinuria. Extrarenal manifestations were pres- ent in 12 patients (21.8%). 36(65.4%) patients had a family history of Alport syndrome. 32 patients underwent pathological examination and 23 of them had the specific pathological changes of Alport syndrome. In 55 cases, 36 (65.4%) were diagnosed as X-linked Alport syndrome, 5(9.1%) were diagnosed as autosomal recessive Alport syndrome, 10(18.2%) were diagnosed as autosomal dominate Alport syndrome, and 4(7.3%) were diagnosed as digenic Alport syndrome. Missense mutations in COL4A genes accounted for 62.5%, 67.5% of missense mutations resulted in glycine substitution. There were statistical significances in proteinuria degree and hearing loss between male and female patients with XLAS (P < 0.05) as well as statistical significance in the degree of proteinuria between autosomal recessive Alport syndrome and autosomal dominate Alport syndrome (P=0.044), and there was critical statistical significance in the age of onset. There was statistical significance in hearing loss between children with renal impairment and children with normal renal function (P=0.001). Conclusions Most of the pathogenic variants in COL4A genes that cause Alport syndrome result in glycine substitutions. The degree of proteinuria and hearing loss of males with XLAS were greater than those of females. The degree of proteinuria in autosomal recessive Alport syndrome was greater than that of children with autosomal dominate Alport syndrome, and the age of onset was earlier than that of autosomal dominate Alport syndrome. Renal manifestation was more severe in children with hearing loss. The early clinical manifestations of Alport syndrome are diverse and pathological manifestations may be atypical. The application of next-generation sequencing can reduce misdiagnosises of Alport syndrome.

BACKGROUND: The most current application of compound porcine cerebroside and ganglioside injection (CPCGI) focuses on the clinical therapeutic efficacy in some craniocerebral injuries and neonatal hypoxic ischemic encephalopathy, but the molecular mechanism of CPCGI involved in the recovery of nerve function is rarely reported. OBJECTIVE: To study the protective effect and mechanism of CPCGI in a neonatal mouse model of intrauterine hypoxia-induced brain injury. METHODS: Fifteen Kunming mice were randomly divided into control group, hypoxia group and treatment group. At the 14thday after pregnancy, mice in hypoxia group and treatment group were put into a 10% oxygen incubator to make the model of intrauterine hypoxia. After delivery, neonatal mice were intraperitoneally injected with CPCGI and PBS respectively, and mouse development in each group was observed after treatment. Mice in the control group were not hypoxic and treated. The expression of glial fibrillary acidic protein, Neurocan, SynDIGI and collagen IV were observed by immunofluorescence staining and western blot assay. A step-down test was used to test animal memory function. The study protocol was approved by the Animal Ethic Committee of Luohe Medical College in China. RESULTS AND CONCLUSION: Compared with the control group, the expressions of glial fibrillary acidic protein and Neurocan in the hypoxia group were significantly increased, while the expressions of SynDIG1 and collagen IV were significantly decreased. The expression of SynDIG1 and collagen IV in the treatment group was significantly increased than that in the hypoxia group, while the expression of glial fibrillary acidic protein and Neuroncan was significantly decreased than that in the hypoxia group. The learning and memory ability of mice in the hypoxia group was significantly decreased compared with the control group, but was significantly improved after CPCGI treatment. These results suggest that CPCGI can alleviate brain injury and improve learning and memory ability after hypoxic ischemic encephalopathy. The detailed mechanism might be related to inhibiting activation of astrocytes, down-regulating Neuroncan expression, up-regulating collagen IV expression, promoting synaptic reconstruction and reducing cerebrovascular injury. [ABSTRACT FROM AUTHOR]

Objective T0 observe the effect of overexpressing suppressor of cytokine signaling 2 (SOCS2) on the expression of transforming growth factor B (TGF-B) , Collagen IV and fibronectin (FN) in human glomerular mesangial cells (HMCs) and to investigate its possible mechanisms. Methods HMCs cultured in vitro were divided into groups A, B , C , D, E and F. Groups A and B were respectively added with Ad-SOCS2 venom (containing SOCS2 adenovirus) and Ad-null venom (containing adenovirus) , after 24 h, we changed the nutrient solution into high glucose solution; group C was added with 3O mmol/L D-glucose; groups D and E were respectively added with Ad-SOCS2 venom and Ad-null venom, after 24 h, we changed the venom into conventional solution; group F was added with 5. 5 mmol/L D-glucose + 24. 5 mmol D-mannitol. Western blotting was used to detect the TGF-B, Collagen IV , FN and Janus kinase 2 (JAK2) , signal transducer and activator of transcription 3 (STATS) , phosphorylated Janus kinase 2 (p-]AK2) and phosphorylated signal transducer and activator of transcription 3 (p-STATS) . Results Compared with group F, the expression of TGF-B, Collagen IV , FN, p-]AK2, and p-STATS was significantly increased in the groups A, B and C; compared with group C, the expression of TGF-B, Collagen IV , FN, p-]AK2 and p-STATS in the group A was significantly decreased (all P <0. O1). C0nClllsi0n SOCS2 can down-regulate the expression of TGF-B, Collagen IV and FN in HMCs by inhibiting JAK/ STAT signaling pathway. [ABSTRACT FROM AUTHOR]

Objectives: Stably expressed transforming growth factor -beta 1(TGF-β1)MCs were obtained and the effects of centellaasiatica (CA) granule on the expressions of Smad 2/3, Smad 7 and collagen Ⅳ and the level of Smad 2/3 phosphorylation were observed., Methods: Lipofectin method was used to transfect TGF-β1 vector into MC, and the stably expressed TGF-β1 cell lines were selected by G418. The cells were divided into three groups. Control group:normal MC + RPMI 1640 + 10% normal rat serum; TGF-β1 group:stably expressed TGF-β1 MC + RPMI 1640 + 10% normal rat serum; CA group:stably expressed TGF-β1 MC + RPMI 1640 + 10% rat serum containing high CA. The experiments were repeated for five times. The contents of TGF-β1 and collagen Ⅳ in the culture medium were detected with ELISA, the expressions of mRNA and protein of TGF-β1, Smad 2/3, Smad 7 and the level of Smad 2/3 phosphorylation were detected by using real time quantitative polymerase chain reaction and Western blot., Results: The contents of TGF-β1 and collagen Ⅳ in the culture medium of stably-expressed TGF-β1 MC were increased significantly, and the CA could reverse the effects of TGF-β1. The expressions of mRNA and protein of TGF-β1, Smad 2/3 and the level of Smad 2/3 phosphorylation were increased significantly in TGF-β1 transfected MC, and CA could dramatically reduce the expressions of mRNA and protein of TGF-β1, Smad 2/3 and the level of Smad 2/3 phosphorylation. The high expression of TGF-β1 decreased the expression of Smad 7 mRNA and protein, and the CA could antagonize the effect of mRNA expression., Conclusions: The MCs stably-expressed TGF-β1 can activate the TGF-β1/Smad signal pathway and increase the expression of collagen Ⅳ. CA can decrease the occurrence of diabetic nephropathy(DN) by reducing the production of collagen Ⅳ through inhibiting the TGF-β1/Smad signal pathway.