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ObjectiveTo investigate the intervention effect of Jiedu Tongluo Tiaogan prescription (JTTP) in protecting pancreatic β cells by targeting the bile acid Takeda G protein-coupled receptor 5 (TGR5)/cyclic adenosine monophosphate (cAMP) signaling pathway against NOD-like receptor protein 3 (NLRP3) inflammasome. MethodThirty-two male SPF-grade db/db mice were randomly divided into the model group, low-dose JTTP group (3.6 g·kg-1), high-dose JTTP group (7.2 g·kg-1), and metformin group (0.2 g·kg-1). Eight db/m mice were assigned to the blank control group. The mice were treated with drugs for 8 weeks, and fasting blood glucose (FBG) was measured every 2 weeks. Oral glucose tolerance tests (OGTT) were conducted after the last administration. Enzyme-linked immunosorbent assay (ELISA) was performed to detect fasting insulin (FINS), and the homeostasis model assessment of β-cell function (HOMA-β), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and IL-1β levels were calculated. Hematoxylin-eosin (HE) staining was used to observe pathological changes in mouse pancreatic tissue. Immunofluorescence was performed to detect insulin expression in mouse pancreatic tissue. Western blot and real-time quantitative polymerase chain reaction (Real-time PCR) were used to detect the expression of proteins and mRNAs of key targets in the TGR5/cAMP signaling pathway and NLRP3 inflammasome. ResultCompared with blank group, FBG, OGTT, FINS, IL-6, TNF-α and IL-1β in model group were significantly increased (P<0.01). Compared with model group, after 6 weeks of drug treatment, FBG level in JTTP group and metformin group decreased significantly (P<0.01). The results of OGTT experiment showed that compared with model group, the blood glucose levels of mice in each administration group were decreased at all time points (P<0.05, P<0.01), and the levels of FINS, TNF-α and IL-6 in JTTP dose groups and metformin group were significantly decreased. The level of IL-1β in JTTP high-dose group and metformin group was significantly decreased (P<0.01). Pancreatic pathology showed that the islets in the model group were irregular in shape, uneven in distribution, and showed signs of atrophy. The prognosis of JTTP was that the cell count increased and the boundary was clearer. Immunofluorescence results showed that the islet cells in the blank group were arranged in an orderly and full shape with appropriate insulin secretion, while the islet cells in model group were distorted in shape, atrophy in structure and less insulin secretion. The insulin content of mice in JTTP and metformin group was significantly increased. Compared with blank group, mRNA expressions of NLRP3, apoptosis-related spot-like protein (ASC) and Caspase-1 in pancreatic tissues of model group were significantly increased (P<0.01). Compared with model group, JTTP high-dose group and metformin group promoted the up-regulation of TGR5 and cAMP mRNA, and down-regulated the mRNA expressions of NLRP3, ASC and Caspase-1 (P<0.05, P<0.01). Compared with blank group, the expression of TGR5 protein in model group was significantly decreased (P<0.01). Compared with model group, TGR5 protein in JTTP high-dose group and metformin group was significantly increased (P<0.01).
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OBJECTIVE@#To explore the clinical and genetic characteristics of three children with KBG syndrome.@*METHODS@#Clinical data of the three children from two families who have presented at the First Affiliated Hospital of Zhengzhou University between October 2019 and September 2020 and their family members were collected. Trio-whole exome sequencing (trio-WES) and Sanger sequencing were carried out.@*RESULTS@#All children had feeding difficulties, congenital heart defects and facial dysmorphism. The sib- pair from family 1 was found to harbor a novel de novo heterozygous c.6270delT (p.Q2091Rfs*84) variant of the ANKRD11 gene, whilst the child from family 2 was found to harbor a novel heterozygous c.6858delC (p.D2286Efs*51) variant of the ANKRD11 gene, which was inherited from his mother who had a mild clinical phenotype.@*CONCLUSION@#The heterozygous frameshift variants of the ANKRD11 gene probably underlay the disease in the three children. Above findings have enriched the spectrum of the ANKRD11 gene variants.
Subject(s)
Female , Child , Humans , Abnormalities, Multiple/genetics , Intellectual Disability/genetics , Bone Diseases, Developmental/genetics , Tooth Abnormalities/genetics , Facies , Repressor Proteins/genetics , Mothers , MutationABSTRACT
OBJECTIVE@#To explore the clinical and genetic features of a child with autosomal dominant mental retardation type 40 (MRD40) due to variant of the CHAMP1 gene.@*METHODS@#Clinical characteristics of the child were analyzed. Genetic testing was carried out by low-depth high-throughput and whole genome copy number variant sequencing (CNV-seq) and whole exome sequencing (WES). A literature review was also carried out for the clinical phenotype and genetic characteristics of patients with MRD40 due to CHAMP1 gene variants.@*RESULTS@#The child, a 11-month-old girl, has presented with intellectual and motor developmental delay. CNV-seq revealed no definite pathogenic variants. WES has detected the presence of a heterozygous c.1908C>G (p.Y636*) variant in the CHAMP1 gene, which was carried by neither parent and predicted to be pathogenic. Literature review has identified 33 additional children from 12 previous reports. All children had presented with developmental delay and mental retardation, and most had dystonia (94.1%), delayed speech and/or walking (85.2%, 82.4%) and ocular abnormalities (79.4%). In total 26 variants of the CHAMP1 gene were detected, with all nonsense variants being of loss-of-function type, located in exon 3, and de novo in origin.@*CONCLUSION@#The heterozygous c.1908C>G (p.Y636*) variant of the CHAMP1 gene probably underlay the WRD40 in this child. Genetic testing should be considered for children featuring global developmental delay, mental retardation, hypertonia and facial dysmorphism.
Subject(s)
Humans , Intellectual Disability/genetics , Genetic Testing , Phenotype , Exome Sequencing , Heterozygote , Mutation , Chromosomal Proteins, Non-Histone/genetics , Phosphoproteins/geneticsABSTRACT
Objective:To detect and analyze the gene variation types of 64 unrelated pedigrees affected with autosomal dominant polycystic kidney disease (ADPKD), and explore the detection efficiency of multiple gene analysis techniques and variation characteristics.Methods:It was a cross-sectional study. The clinical data of 64 pedigrees with ADPKD from Nephrology Department or Genetic and Prenatal Diagnosis Center of the First Affiliated Hospital of Zhengzhou University from December 2017 to August 2020 were retrospectively analyzed. The blood samples of probands and other family members were collected. Genetic analysis was carried out by next generation sequencing, and suspected mutations were verified by multiplex ligation-dependent probe amplification, or long-range PCR combined with Sanger sequencing. Prenatal diagnosis for high-risk fetuses was performed by fetal villi or amniotic fluid cells after genotyping without maternal genomic DNA contamination.Results:Among detected 64 pedigrees, 57 pedigrees (89.06%) had genetic variants in PKD1/PKD2. A total of 49 pathogenic/likely pathogenic variants in PKD1/PKD2 were identified in 51 pedigrees (79.69%), including 14 nonsense variants (28.57%), 14 frameshift variants (28.57%), 11 missense variants (22.45%), 5 splicing variants (10.20%) and 5 deletion variants (10.20%). Of these variants, 87.76% (43/49) were in PKD1 and 12.24% (6/49) were in PKD2. Totally, 14 novel variants in PKD1/ PKD2 were identified, including 7 frameshift variants, 3 splicing variants, 2 nonsense variants, 1 deletion variant and 1 missense variant, of which 11 variants were in PKD1 and 3 variants were in PKD2. Twenty high-risk fetuses from 17 pedigrees received prenatal diagnosis, in whom 6 fetuses had PKD1 variation, and other 14 fetuses had no PKD1/ PKD2-genetic variation. Conclusions:The combination of next-generation sequencing, multiplex ligation-dependent probe amplification, and long-range PCR combined with Sanger sequencing can be helpful for rapid, efficient and accurate genetic diagnosis of ADPKD pedigrees. Point mutations are the most common types in PKD1/PKD2. Fourteen novel variants in PKD1/PKD2 extend its pathogenic variant spectrum and can provide basis for genetic counseling and prenatal diagnosis of ADPKD pedigrees.
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Objective To understand the basic situation and existing problems of cost accounting information construction in the traditional Chinese medicine hospital. Methods We made a cross-sectional study of all traditional Chinese medicine hospitals cost accounting informatization, and then analyzed the results. Results In the survey of 1588 traditional Chinese medicine hospitals, there exists the problem with 78.65%for limited software;57.43%for not sharing between the systems;43.20%for outdated software. The occupancy rate was 81.86%for HIS system, 87.09%for the accounting software, 39.11%for cost accounting software, 5.42%for none. The proportion of hospitals was over 95% whose income data statistics to department;80% for spending data;73.05%for fixed assets depreciation cost;51.39%for amortization of intangible assets and 52.77%for medical risk fund. The proportion of hospitals was 81.49%whose data inside services statistics to medical auxiliary departments and higher than the logistics department, which was 63.85%.Conclusion The occupancy rate of cost accounting system software was limited in traditional Chinese medicine hospitals. The problems were limited cost accounting system software and unavailable information shared between the systems.