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The actual Productivity of Hydroxychloroquine for the treatment Main Sjögren's Symptoms: A Systematic Assessment as well as Meta-Analysis.
Objective To understand the clinical phenotype and spectrum of ATP7B gene mutation in children with Wilson's disease (WD). Methods A total of 55 cases diagnosed with WD at the Children's Hospital Affiliated to Nanjing Medical University from June 2012 to June 2018 were taken as the research subject. ATP7B gene point mutation was detected by direct sequencing after PCR amplification. Heterozygous mutation in children was discovered by sequencing. Furthermore, the long segment mutation of exon was analyzed by multiplex ligation-dependent probe amplification (MLPA). Results All 55 WD children had varying degree of liver damage symptoms. Among them, 2 cases had combined neurological symptoms. The positive rates of K-F ring (21%), 24-hour urine copper (97.7%), and ceruloplasmin were all abnormal. The results of ATP7B gene had identified 8 homozygous, 41 compound heterozygous and 6 heterozygous in 55 cases. Direct sequencing method had detected ten cases of ATP7B heterozygotes. In addition, MLPA analysis showed that other allele in four cases had a deletion of the ATP7B gene exon. In all cases, 35 different ATP7B gene mutations were detected, including 23 missense mutations, 3 frameshift mutations, 4 nonsense mutations, 3 exon deletions and 2 splicing changes. The most common allele mutation was c.2333G > T/p.R778L in exon 8, with an allele frequency of 36.54%, followed by c.2975C > T/p.P992L in exon 13, with an allele frequency of 14.42%. learn more ConclusionATP7B gene c.2333G > T/p.R778L and c.2975C > T/p.P992L mutations are the most common mutations in children with WD in China. WD patients report shows that there are three long deletion mutations in the exon of the ATP7B gene. For WD children whose DNA sequencing is heterozygous ATP7B gene, it is suggested to further use MLPA method to detect deletion mutations of exons.Objective To explore the correlation between the body mass index (BMI) trajectories and new-onset non-alcoholic fatty liver disease (NAFLD) so as to provide a scientific basis for the prevention and treatment of NAFLD. Methods A total of 16388 observation subjects that met the inclusion criteria in the Kailuan study were used to form a cohort study. According to the BMI values of the observed subjects during annual physical examinations from 2006 to 2007, 2008 to 2009 and 2010 to 2011, SAS Proc Traj was used to determine four different BMI trajectories groups, namely, the low-stable medium-stable, medium-high and high-stable group. NAFLD incidence in each group was followed up during annual physical examinations from 2012 to 2013, 2014-2015 and 2016-2017. A total of 14998 observation subjects were finally included in the statistical analysis. The cumulative incidences of NAFLD differences in the four groups were compared. The Cox's proportional hazards regression model was used to analyze the correlation betw) of the low-stable group (P less then 0.01). Conclusion The risk of NAFLD increases with increase of BMI trajectories, and long-term high levels of BMI are independent risk factors for the onset of NAFLD.Objective To construct a transmembrane 6 superfamily member 2 (Tm6sf2) E167K gene knock-in mouse model. Methods The plasmid was constructed to simultaneously express the single-stranded guide RNA Cas9 at a specific site of the mouse Tm6sf2 gene in the donor plasmid carrying the Tm6sf2 E167K fragment. The above two plasmids were injected into the mouse fertilized eggs together. The positive F0 generation mice were validated by PCR detection and sequencing. The number of F2 generation surviving mice in three genotypes of wild (Wt), heterozygous and knock-in (KI) were calculated. Wt and KI male mice (8 mice/ group) of F2 generation littermates were selected and given a normal diet for 8 weeks. The body weight of the mice was recorded every week, and the glucose metabolism and lipid metabolism indexes of the two mice were detected. The comparison between groups was performed with an independent sample t-test. Results Genotype detection and sequencing results showed that the Tm6sf2 E167K gene knock-in mouse model was successfully established. KI mice had absence of homozygous lethal embryo phenotype. The body weight of KI mice was higher than that of Wt mice during lactation, and the difference between the two groups was statistically significant (P 0.05). The Oil red O staining results showed that KI mice had more lipid accumulation in the centrilobular region of liver than Wt mice. Conclusion Tm6sf2 E167K gene knock-in mice were successfully constructed. Tm6sf2 E167K gene knock-in can cause abnormal glucose metabolism in mice and promote the occurrence of hepatic steatosis.Objective To explore the effect of HBV preC/C and S gene antigen epitope mutations on HBeAg serological status in patients with chronic hepatitis B. Methods Thirty-five cases with chronic hepatitis B without antiviral therapy were enrolled in this cross-sectional study. Nested PCR-TA cloning-sequencing method was used to screen HBV preC/C and S gene mutation sites related to HBeAg serological status. Then, in the longitudinal study (60 cases), the independent correlation between HBV preC/C and S gene antigen epitopes mutations and HBeAg status was explored by using multiple regression models to correct the correlated confounding factors. Results In this cross-sectional study, 64.4% of preC/C and 68.2% of S mutations had occurred in the epitope region. There were ten mutation sites (PreC/C50, 55, 79, 84, 103, 126, 145, 184 and s110, s213) correlated with HBeAg negative status (P less then 0.05). After adjusting for confounding factors such as age, gender, HBV genotype, serum alanine aminotransferase level and precw28 * mutations in the longitudinal studies, the results showed that TC cell epitope (prec47-56, prec117-125, s208-216) and Th cell epitope (prec176-185) were the main independent risk factors affecting the host HBeAg serological status. Conclusion HBV preC/C region (PreC47-56, PreC117-125 and PreC176-185) and S region (s208-216) epitope mutations are the main independent factors affecting the host HBeAg status, suggesting that these epitope mutations may be involved in the HBeAg seroconversion.
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