Objective:To explore the effects of gentiana scabra bage on the expression of hepatic collagen proteins in Paragonimus skrjabinirats with liver fibrosis.Methods:Immunohistochemical technique was used to observe the changes of content of hepatic type Ⅰ, Ⅱ collagen proteins in Paragonimus skrjabinirats with liver fibrosis before and after the gentiana scabra bage treatmeat. Results:Comparing with the model group, changes of hepatic type Ⅰand type Ⅱ collagen proteins in gentiana scabra bage treated group were significantly weakened.Conclusions:Gentiana scabra bage treatment can reduce the content of hepatic type Ⅱ and typeⅠcollagen protein significantly in Paragonimus skrjabinirats with liver fibrosis, thereby, playing the role against hepatic fibrosis.

Objective To understand the characteristics of High-density lipoprotein cholesterol (HDL-C) distribution through analyzing serum HDL-C levels in healthy checkup subjects among local urbanese.Methods The checkup results of 36 454 cases were collected from 2009 to 2013 in Tangshan Gongren hospital (male:n =20 343,female:n =16 111).The cases with liver injury,abnormal blood glucoses,kidney injury and defined cerebrovascular diseases and metabolic disease were excluded.25 197 cases were analyzed as normal subjects including 11 114 males and 14 083 females.Kolmogorov-Smimov test,kruskal-wallis test,and Dunn multiple comparison test was performed using Bioconductor software 3.0.2 for testing normality distribution and comparing the difference of two or multiple groups,respectively.Results were analyzed statistically with R 3.0.2.Results The results showed that the average level (1.22-± 0.31) mmol/L of HDL-C among the overall population is lower than that of national average level(1.30 mmol/L).The median serum HDL-C level in female is higher than in male (1.27 and 1.08,x2 =2 606.34,P ＜0.01).HDL-C levels in male continuously increase from 1.06 mmol/L to 1.11 mmol/L with aging,especially in groups of over 50 years old than in groups of below 50 years old (x2 =75.19,P ＜ 0.01).Conclusions Based on 2007 guidance on prevention and treatment by national health bureau,this study showed that there are 29.69％ of the apparent healthy subjects,especially about 42.94％ of the male,representing low HDL-C level under the low limit of 1.04 mmol/L.These results showed that serum HDL-C level in Tangshan urbanese is lower than that of national average level,and HDL-C level in male is tended to increase with aging.

Objective:To explore the clinical manifestation, efficacy and treatment strategies in patients with severe warm autoimmune hemolytic anemia (w-AIHA).Methods:A total of 21 patients with w-AIHA who were hospitalized in Children′s Hospital of Capital Institute of Pediatrics from June 2007 to March 2019 were included, and the clinical characteristics, treatment strategies and responses were retrospectively analyzed.Results:A total of 21 children with severe w-AIHA had an average age of 8.0 (2.5, 20.0) months and a follow-up time of 33.0 (18.5, 110.0) months.In 10 (47.6%) cases, the hemoglobin levels were lower than 30 g/L.Evans′ syndrome was diagnosed in five(23.8%) cases.Five (23.8%) cases were secondary cases.Nine (42.8%) cases had a previous infection history and two cases were pollen-induced.Five (23.8%) cases had hemolytic crisis.A total of 12 (57.1%) cases had cross-matching difficulty.Eight (38.1%) cases were admitted to the ICU, and five (23.8%) cases had shock.All children received corticosteroids and intravenous immunoglobulin, 16 (76.2%) cases were treated with second-line regimens (cyclophosphamide and rituximab, etc.), 15 cases had complete response, three cases had partial response and three cases had no response and died.Conclusion:Infection is an important predisposing factor in children with severe w-AIHA, and secondary cases have a higher proportion, mainly caused by immunodeficiency disease.Patients tend to have a high incidence of hemolytic crisis and have difficulty in matching and transfusion.Therefore, transfusion is the key for successful rescue.It is suggested that children with severe w-AIHA require ICU admission for early monitoring and rituximab should be applied in advance to ensure successful transfusion.

Amyotrophic lateral sclerosis (ALS) is a complex neurodegenerative disease with cellular and molecular mechanisms yet to be fully described. Mutations in a number of genes including SOD1 and FUS are associated with familial ALS. Here we report the generation of induced pluripotent stem cells (iPSCs) from fibroblasts of familial ALS patients bearing SOD1 and FUS mutations, respectively. We further generated gene corrected ALS iPSCs using CRISPR/Cas9 system. Genome-wide RNA sequencing (RNA-seq) analysis of motor neurons derived from SOD1 and corrected iPSCs revealed 899 aberrant transcripts. Our work may shed light on discovery of early biomarkers and pathways dysregulated in ALS, as well as provide a basis for novel therapeutic strategies to treat ALS.
Amyotrophic Lateral Sclerosis ; genetics ; metabolism ; therapy ; Cell Line ; Clustered Regularly Interspaced Short Palindromic Repeats ; Genetic Therapy ; Genome-Wide Association Study ; Humans ; Induced Pluripotent Stem Cells ; metabolism ; Mutation, Missense ; RNA-Binding Protein FUS ; genetics ; metabolism ; Superoxide Dismutase-1 ; genetics ; metabolism

Xeroderma pigmentosum (XP) is a group of genetic disorders caused by mutations of XP-associated genes, resulting in impairment of DNA repair. XP patients frequently exhibit neurological degeneration, but the underlying mechanism is unknown, in part due to lack of proper disease models. Here, we generated patient-specific induced pluripotent stem cells (iPSCs) harboring mutations in five different XP genes including XPA, XPB, XPC, XPG, and XPV. These iPSCs were further differentiated to neural cells, and their susceptibility to DNA damage stress was investigated. Mutation of XPA in either neural stem cells (NSCs) or neurons resulted in severe DNA damage repair defects, and these neural cells with mutant XPA were hyper-sensitive to DNA damage-induced apoptosis. Thus, XP-mutant neural cells represent valuable tools to clarify the molecular mechanisms of neurological abnormalities in the XP patients.
DNA Damage ; DNA Repair ; DNA-Binding Proteins ; genetics ; metabolism ; Female ; Humans ; Induced Pluripotent Stem Cells ; metabolism ; pathology ; Male ; Models, Biological ; Mutation ; Neural Stem Cells ; metabolism ; pathology ; Xeroderma Pigmentosum ; genetics ; metabolism ; pathology

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a rare hereditary cerebrovascular disease caused by a NOTCH3 mutation. However, the underlying cellular and molecular mechanisms remain unidentified. Here, we generated non-integrative induced pluripotent stem cells (iPSCs) from fibroblasts of a CADASIL patient harboring a heterozygous NOTCH3 mutation (c.3226C>T, p.R1076C). Vascular smooth muscle cells (VSMCs) differentiated from CADASIL-specific iPSCs showed gene expression changes associated with disease phenotypes, including activation of the NOTCH and NF-κB signaling pathway, cytoskeleton disorganization, and excessive cell proliferation. In comparison, these abnormalities were not observed in vascular endothelial cells (VECs) derived from the patient's iPSCs. Importantly, the abnormal upregulation of NF-κB target genes in CADASIL VSMCs was diminished by a NOTCH pathway inhibitor, providing a potential therapeutic strategy for CADASIL. Overall, using this iPSC-based disease model, our study identified clues for studying the pathogenic mechanisms of CADASIL and developing treatment strategies for this disease.