Abstract: Objective To elucidate the potential mechanism of Jindanjiangan Capsule in the treatment of liver fibrosis by network pharmacology and molecular docking. Methods Active ingredients and targets of Jindanjiangan Capsules were searched by Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) and HERB databases, and the disease targets were screened by DisGeNET and Therapeutic Target Database (TTD) databases. The targets of the active ingredients of Jindanjiangan Capsule were matched with the disease targets, and the common targets were imported into the String database platform to construct a protein-protein interaction network (PPI) network. CytoNCA tool of Cytoscape 3.9.1 software was used for topological analysis to screen key targets. Traditional Chinese Medicine-Key Active IngredientsKey Target Network was constructed by Cytoscape 3.9.1 Software. KEGG enrichment analysis of key targets was performed through the DAVID platform. The molecular docking of active ingredients and targets was performed to verify the above results using LeDock software. Results By screening, 180 potential active ingredients and 1 340 targets of Jindanjiangan Capsule and 1 060 targets of liver fibrosis, and 273 common targets were obtained. 29 key targets related to liver fibrosis were screened out by PPI network interaction, and verified by KEGG analysis and molecular docking. Jindanjiangan capsule acts on key targets such as EGFR, MMP9, PTGS2, ESR1, PIK3CA, F2, PPARG, and PTPN11 through active components such as isovitexin, quercetin 7-O- β -D-glucoside, (3S, 6S) -3- (benzyl) -6- (4-hydroxybenzyl) piperazine-2, 5-quinone, 6-Osyringoyl-8-O-acetylshanzhiside methyl ester, tanshinone II, nortanshinone, capillaris chromone, and etanone. The specific mechanism may be related to HIF-1 signaling pathway, C-type lectin receptor signaling pathway, Toll-like receptor signaling pathway, tumor necrosis factor signaling pathway, relaxin signaling pathway, FoxO signaling pathway and so on. Conclusion Jindanjiangan capsule can effectively treat hepatic fibrosis through multi-component, multi-target and multi-pathway.

Congenital cataract is one of the important reasons for the blindness of children,and most congenital cataracts are genetic.At present,thirty-nine genes have been identified relating to autosomal dominant congenital cataract (ADCC).Objective This study was to identify and analyze the virulence gene of a Chinese family pedigree with ADCC by whole-exome sequencing.Methods A Chinese ADCC family was recruited in Affiliated First Hospital of Zhengzhou University from August to September in 2014.The family disease history and clinical data were recorded.The peripheral venous blood of 10 ml was collected in 14 patients with congenital cataract and 14 families with normal phenotype,and the peripheral blood samples were obtained from 100 healthy examined people as controls.The genomic DNA was extracted form all subjects using standard phenol chlorum method,and proband DNA was screened by whole-exome sequencing.Then mutation locus of the candidate gene was selected after compared with the information of database in the proband.The mutation locus of the candidate gene from 14 normal families and 100 healthy controls were amplified and sequenced by PCR technique based on the primer sequence of mutation locus of proband to verify the pathogenic gene of this ADCC family.This study protocol was approved by Ethic Committee of Affiliated First Hospital of Zhengzhou University and complied with Helsinki Declaration.Written informed consent was obtained from subjects or custodian before any medical examination.Results The family had a total of 5 generations of 68 members,in which 20 subjects were found with congenital cataract.The inheritance mode consisted with autosomal dominant inheritance.Cortical cataract was found in both eyes in the patients.Whole-exome sequencing showed that the 143rd ribonucleotide A of exon 2 explicit factor of chromosome 13 GJA3 gene mutated into G (c.143A＞G) in the proband,which resulted in the 48th amino acids changed from glutamate into glycine (p.E48G).PCR amplification product sequencing displayed that the same mutation of DNA appeared in all the patients of this family,while not the same mutation was seen in the candidate genes of normal phenotype families and 100 healthy controls.Conclusions GJA3 gene c.143A＞G is a virulence mutation site in this ADCC family,it is a supplement of the mutation spectrum of GJA3 gene.

Objective:To characterize the histopathological subtypes and their clinicopathological parameters of gender and onset age by common, rare and sparse primary esophageal malignant tumors (PEMT).Methods:A total of 272 437 patients with PEMT were enrolled in this study, and all of the patients were received radical surgery. The clinicopathological information of the patients was obtained from the database established by the State Key Laboratory of Esophageal Cancer Prevention & Treatment from September 1973 to December 2020, which included the clinical treatment, pathological diagnosis and follow-up information of esophagus and gastric cardia cancers. All patients were diagnosed and classified by the criteria of esophageal tumor histopathological diagnosis and classification (2019) of the World Health Organization (WHO). The esophageal tumors, which were not included in the WHO classification, were analyzed separately according to the postoperative pathological diagnosis. The χ 2 test was performed by the SPSS 25.0 software on count data, and the test standard α=0.05. Results:A total of 32 histopathological types were identified in the enrolled PEMT patients, of which 10 subtypes were not included in the WHO classification. According to the frequency, PEMT were divided into common (esophageal squamous cell carcinoma, ESCC, accounting for 97.1%), rare (esophageal adenocarcinoma, EAC, accounting for 2.3%) and sparse (mainly esophageal small cell carcinoma, malignant melanoma, etc., accounting for 0.6%). All the common, rare, and sparse types occurred predominantly in male patients, and the gender difference of rare type was most significant (EAC, male∶ female, 2.67∶1), followed with common type (ESCC, male∶ female, 1.78∶1) and sparse type (male∶ female, 1.71∶1). The common type (ESCC) mainly occurred in the middle thoracic segment (65.2%), while the rare type (EAC) mainly occurred in the lower thoracic segment (56.8%). Among the sparse type, malignant melanoma and malignant fibrous histiocytoma were both predominantly located in the lower thoracic segment (51.7%, 66.7%), and the others were mainly in the middle thoracic segment.Conclusion:ESCC is the most common type among the 32 histopathological types of PEMT, followed by EAC as the rare type, and esophageal small cell carcinoma and malignant melanoma as the major sparse type, and all of which are mainly occur in male patients. The common type of ESCC mainly occur in the middle thoracic segment, while the rare type of EAC mainly in the lower thoracic segment. The mainly sparse type of malignant melanoma and malignant fibrous histiocytoma predominately occur in the lower thoracic segment, and the remaining sparse types mainly occur in the middle thoracic segment.