Objective: To explore the heterogeneity and correlation of clinical phenotypes and genotypes in children with disorders of sex development (DSD). Methods: A retrospective study of 1 235 patients with clinically proposed DSD in 36 pediatric medical institutions across the country from January 2017 to May 2021. After capturing 277 DSD-related candidate genes, second-generation sequencing was performed to analyzed the heterogeneity and correlation combined with clinical phenotypes. Results: Among 1 235 children with clinically proposed DSD, 980 were males and 255 were females of social gender at the time of initial diagnosis with the age ranged from 1 day of age to 17.92 years. A total of 443 children with pathogenic variants were detected through molecular genetic studies, with a positive detection rate of 35.9%. The most common clinical phenotypes were micropenis (455 cases), hypospadias (321 cases), and cryptorchidism (172 cases) and common mutations detected were in SRD5A2 gene (80 cases), AR gene (53 cases) and CYP21A2 gene (44 cases). Among them, the SRD5A2 mutation is the most common in children with simple micropenis and simple hypospadias, while the AMH mutation is the most common in children with simple cryptorchidism. Conclusions: The SRD5A2 mutation is the most common genetic variant in Chinese children with DSD, and micropenis, cryptorchidism, and hypospadias are the most common clinical phenotypes. Molecular diagnosis can provide clues about the biological basis of DSD, and can also guide clinicians to perform specific clinical examinations. Target sequence capture probes and next-generation sequencing technology can provide effective and economical genetic diagnosis for children with DSD.
3-Oxo-5-alpha-Steroid 4-Dehydrogenase/genetics* ; Child ; China/epidemiology* ; Cryptorchidism/genetics* ; Disorders of Sex Development/genetics* ; Female ; Genital Diseases, Male ; Genotype ; Humans ; Hypospadias/genetics* ; Male ; Membrane Proteins/genetics* ; Penis/abnormalities* ; Phenotype ; Retrospective Studies ; Steroid 21-Hydroxylase/genetics*

Golgi protein 73 (GP73) is a transmembrane protein on the Golgi apparatus and can be cut and released into the blood. In recent years, an increasing number of clinical studies have shown that the elevated serum GP73 level is closely related to liver diseases. And thus GP73 is expected to be used as a new serum marker for assessing progress of chronic liver diseases. Herein, the clinical application of serum GP73 in chronic hepatitis, liver fibrosis, liver cirrhosis and hepatocellular carcinoma with different etiologies was reviewed based on available literatures; and a research outlook in this field is made.
Biomarkers ; Carcinoma, Hepatocellular ; Golgi Apparatus ; Humans ; Liver Cirrhosis ; Liver Neoplasms

The liver is abundant in blood supply and receives 25% of the cardiac output via the hepatic artery and portal vein. Circulatory disorders may cause hepatic injury, resulting in congestive hepatopathy(CH) and ischemic hepatitis(IH). Hepatic congestion arising from increased hepatic venous pressure and decreased cardiac output is the common pathophysiological basis of both CH and IH. In addition, extensive arteriovenous shunts affect portal pressure and cardiac function, leading to alterations of hepatic blood supply. The current review summarizes the pathophysiology, clinical manifestations and therapeutic interventions of the above diseases, in order to provide reference for clinical practice.
Cardiovascular Diseases ; Hepatic Artery ; Humans ; Liver ; Liver Diseases ; Portal Pressure ; Portal Vein

Huang-Qin Decoction (HQD) is a classic prescription for diarrhea in Chinese medicine treatment. Recent studies have demonstrated that HQD and its modified formulation PHY906 could ameliorate irinotecan (CPT-11) induced gastrointestinal (GI) toxicity and enhance its anticancer therapeutic efficacy. Nevertheless, which constituents in HQD are effective is still unclear so far. The study aims to screen out the key bioactive components combination from HQD that could enhance the anticancer effect of CPT-11. First, the potential bioactive constituents were obtained through system pharmacology strategy. Then the bioactivity of each constituent was investigated synthetically from the aspects of NCM460 cell migration, TNF-α release of THP-1-derived macrophage and MTT assay in HCT116 cell. The contribution of each constituent in HQD was evaluated using the bioactive index E

Objective::In this study, a network pharmacology-based method was applied to analyze the mechanism of modified Erzhiwan combined with epimedium in treatment of atherosclerosis. Method::The compounds and targets of modified Erzhiwan combined with epimedium were screened in traditional Chinese medicine(TCM) systems pharmacology database and analysis platform (TCMSP) and bioinformatics analysis tool for molecular mechanism of TCM (BATMAN-TCM). Mang related databases were applied to find the target-related to atherosclerosis.The common targets of modified Erzhiwan combined with epimedium and atherosclerosis were got by venn diagrams.Cytoscape 3.6.1 was used to construct ingredients-disease-targets networks.Then protein-protein interaction (PPI) analysis of ingredients-disease-targets was builed in STRING database, and was visualized by Cytoscape 3.6.1, then important modules were analyzed with Moleculaar complex detection(MCODE). Biological information annotation databases (DAVID) was used to carry on gene ontology (GO) analysis and enrichment analysis of gene encyclopedia kyoto encyclopedia of genes and genomes (KEGG) pathway. Result::A total of 38 active ingredients and 266 potential targets of modified Erzhiwan combined with epimedium were obtained from TCMSP and BATMAN-TCM, 254 atherosclerosis-related targets were retrieved from disease database.Then 52 common targets were obtained and 14 core genes were screened.Biological processes were related to inflammatory response, regulation of insulin secretion, positive regulation of nitric oxide biosynthetic process, etc.The biological pathways mainly included tumor necrosis factor signaling pathway, NF-kappa B(NF-κB)signaling pathway, peroxisome proliferators-activated receptors signaling pathway and so on. Conclusion::Modified Erzhiwan combined with epimedium may play the anti-atherosclerosis role by estrogen-like effect through attach estrogen receptor, inhibiting inflammation and improving insulin resistance, which may provide guidance for further experimental research.