OBJECTIVETo explore the common causative genes and mutation sites for hereditary non-syndromic deafness in Shanxi.

METHODSPeripheral blood samples were collected from regional schools for children with deafness. The samples were analyzed by matrix-assisted laser desorption ionization of flight mass spectrometry, and the results were verified by DNA sequencing.

RESULTSFor all samples, the 20 mutational sites of the 4 common causative genes were tested. As revealed, c.235delC of GJB2 gene has the highest mutational rate (13.67%). c.IVS7-2A>G of SLC26A (PDS) gene has a mutation rate of 17.67%, and c.1555A>G of mitochondrial 12S rRNA has a mutation rate of 2.00%. No mutations have been found with GJB3 gene. Sequencing analysis has suggested that the above results have a consistency rate of 99%.

CONCLUSIONAnalysis of mutations of the 4 common deafness-related genes can facilitate early diagnosis and treatment for the disease. Matrix-assisted laser desorption ionization time of flight mass spectrometry is a reliable method for such a task.

Adolescent ; Asian Continental Ancestry Group ; genetics ; Base Sequence ; Child ; China ; Connexin 26 ; Connexins ; genetics ; DNA Mutational Analysis ; Deafness ; genetics ; Female ; Humans ; Male ; Molecular Sequence Data ; Mutation ; RNA, Ribosomal ; genetics ; Young Adult

OBJECTIVETo identify novel common mutations among patients with non-syndromic hearing loss (NSHL).

METHODSHigh-throughput gene capture technology was used to analyze 18 patients with NSHL in whom common mutations of deafness genes including GJB2, SLC26A4, GJB3, and mtDNA were excluded. Suspected mutation was verified with Sanger sequencing.

RESULTSNext generation sequencing has identified 62 mutations in 29 genes associated with hearing loss, which included 54 missense mutations, 4 splicing mutations, 3 deletional mutations, and 1 nonsense mutation. Mutations occurring more than twice in the 18 patients were verified by Sanger sequencing. This has confirmed 15 mutations in 8 genes, including 3 missense mutations (p.C2184G, p.L2825P, p.H1888Y) which have not been reported previously. Meanwhile, p.L445W, p.D866N, and IVS919-2A>G were common causative mutations.

CONCLUSIONA number of common causative mutations, e.g., p.L445W, p.D866N, IVS919-2A>G, have been identified by high-throughput capture technology, which may facilitate the research and genetic diagnosis for hearing loss.

DNA, Mitochondrial ; genetics ; Deafness ; genetics ; Female ; Hearing Loss ; genetics ; High-Throughput Nucleotide Sequencing ; methods ; Humans ; Male ; Mutation ; genetics

OBJECTIVE: To assess the association of single nucleotide polymorphisms (SNP) of aquaporin 7 ( AQP7) and aquaporin 9 ( AQP9) genes and type 2 diabetes mellitus (T2DM) among ethnic Han Chinese population. METHODS: A case-control study involving 1194 subjects with T2DM and 1274 non-diabetic mellitus (NDM) subjects were enrolled. Genotypes of three SNPs (rs3758269 of AQP7 gene, rs16939881 and rs57139208 of AQP9 gene) were determined by using a MassArray method. The association of the three SNPs with T2DM was assess, and the correlation of glucose and lipid metabolism parameters with various SNP genotypes in the NDM group was analyzed. RESULTS: The allelic and genotypic frequencies of the three SNPs did not differ significantly between the two groups (P>0.05). Nor was there significant difference between the two groups with different genetic models (P>0.05). No significant association of genotypes of AQP7 gene rs3758269, AQP9 gene rs16939881 and rs57139208 with glucose and lipid metabolism parameters were observed in the NDM group (P>0.05). CONCLUSION The rs3758269 in AQP7 gene and rs16939881 and rs57139208 in AQP9 gene are not associated with the genetic susceptibility of T2DM among ethnic Han Chinese population.
Aquaporins/genetics* ; Case-Control Studies ; China ; Diabetes Mellitus, Type 2/genetics* ; Genetic Predisposition to Disease ; Humans ; Polymorphism, Single Nucleotide

Objective:To investigate the predictive value of serum D-dimer combined with myocardial injury markers on admission for early identification of high-risk patients with acute myocarditis.Methods:Patients hospitalized for acute myocarditis in China-Japan Friendship Hospital were retrospectively enrolled from 2010 to 2021. Patients were divided into the high D-dimer level group and low D-dimer level group according to the median value of D-dimer measured by immunoturbidimetry within 24 h of admission. In-hospital adverse events were defined as death, cardiogenic shock, malignant ventricular arrhythmia and new-onset heart failure. Multivariate logistic analysis was used to explore the independent predictors of in-hospital adverse events, and receiver operating characteristic curve was used to evaluate the predictive value.Results:A total of 106 patients were analyzed, including 52 high level D-dimer patients and 54 low level D-dimer patients, with an average age of (36±16) years, and 62.3% were male. Compared with the low D-dimer level group, patients in the high D-dimer level group had lower mean systolic blood pressure [(114±21) mmHg vs. (121±14) mmHg] and diastolic blood pressure [(71±13) mmHg vs. (76±10) mmHg], higher heart rate [(97±26) beats/min vs. (79±15) beats/min], higher C-reactive protein levels [6.82 (1.61, 20.05) mg/dL vs. 1.30 (0.13, 8.93) mg/dL] and creatinine levels [86.95 (67.63, 117.83) μmol/L vs. 68.80 (60.18, 81.93) μmol/L] on admission. The proportion of patients having QRS interval >120 ms on electrocardiogram was higher in high D-dimer level group (25.0% vs. 7.4%). There was no significant difference in patients with positive myocardial injury biomarkers between the two groups. The incidence of in-hospital adverse events was higher in the high D-dimer level group (67.3% vs. 22.2%, P<0.001). Multivariate logistic analysis showed that serum D-dimer levels and elevated myocardial injury markers on admission were independently associated with in-hospital adverse events. The area under the curve (AUC) of elevated serum D-dimer level on admission for predicting in-hospital adverse events was 0.781 (95% CI: 0.690-0.873), the sensitivity was 74.5%, and the specificity was 71.2%. When combined with positive cardiac biomarkers, the AUC was 0.831 (95% CI: 0.752-0.910) with a sensitivity of 80.9% and a specificity of 78.0%. Conclusions:Elevated D-dimer level on admission can predict the risk of in-hospital adverse events in patients with acute myocarditis. The combination of cardiac injury biomarkers can improve the predictive value.

BACKGROUND:High-methionine diet can cause liver injury in Cbs+/-mice,and hyperhomocystinemia is related to the occurrence and progression of various liver-related diseases,such as hepatic steatosis,autoimmune hepatitis,and alcoholic fatty liver disease.MicroRNAs(miRNAs)are involved in various cellular processes including cell survival,differentiation and autophagy,which are of great significance. OBJECTIVE:To investigate the critical role of miR-144-3p on Cbs+/-mouse hepatocyte autophagy induced by high methionine die. METHODS:(1)Ten male cystathione-β-synthase normal(Cbs+/+)mice and another 10 male mice with single gene knockout(Cbs+/-)of similar body mass,4 weeks of age,were fed a high-methionine diet and executed after 12 weeks to take liver tissue.(2)Human hepatocytes(HL-7702)were cultured in vitro and divided into control[0 μmol/L homocysteine(Hcy)],Hcy(100 μmol/L Hcy),mimic-NC(transfected with mimic-NC),mimic-NC + Hcy(mimic-NC transfecton+100 μmol/L Hcy),miR-144-3p mimic(transfected with miR-144-3p mimic),and miR-144-3p mimic + Hcy(miR-144-3p mimic transfection+100 μ mol/L Hcy),inhibitor-NC(transfected with inhibitor-NC),inhibitor-NC + Hcy(inhibitor-NC transfection + 100 μmol/L Hcy),miR-144-3p inhibitor(transfected with miR-144-3p inhibitor),and miR-144-3p inhibitor + Hcy(miR-144-3p inhibitor transfection + 100 μmol/L Hcy).Quantitative real-time PCR was used to detect the expression of miR-144-3p in liver tissue and hepatocytes.After transfection of miR-144-3p mimic or inhibitor,quantitative real-time PCR and western blot were used to detect the transfection efficiency of miR-144-3p and its effect on the expression of autophagy-related proteins LC3B and p62.The levels of alanine transferase and aspartate aminotransferase in hepatocyte supernatants were determined by enzyme linked immunosorbent assay.The correlation between the expression of miR-144-3 in hepatocyte and the levels of alanine transferase and aspartate aminotransferase in hepatocyte supernatants were analyzed by Pearson correlation analysis. RESULTS AND CONCLUSION:Compared with the Cbs+/+ group and control group,the expression of miR-144-3p in the liver tissue of the Cbs+/-group and in hepatocytes of the Hcy group was decreased(P<0.01).The expression of LC3B-Ⅱ/Ⅰ was decreased in hepatocyte after transfection of miR-144-3p mimic,while the protein expression of p62 was increased(P<0.01).The opposite results were obtained after transfection of miR-144-3p inhibitor(P<0.01).Compared with the mimic-NC group,the levels of alanine transferase and aspartate aminotransferase were decreased in the miR-144-3p mimic group(P<0.01),while the opposite results were obtained in the inhibitor-NC group(P<0.01).The expression of miR-144-3p in hepatocytes was negatively correlated with the levels of alanine transferase(P<0.01,r=-0.887 6)and aspartate aminotransferase(P<0.01,r=-0.829 9)in the supernatant of hepatocytes.To conclude,Hcy promotes hepatocyte autophagy by inhibiting the expression of miR-144-3p,which subsequently aggravates liver injury.

Coronavirus disease 2019(COVID-19),which is caused by SARS-CoV-2,varies with regard to symptoms and mortality rates among populations.Humoral immunity plays critical roles in SARS-CoV-2 infection and recovery from COVID-19.However,differences in immune responses and clinical features among COVID-19 patients remain largely unknown.Here,we report a database for COVID-19-specific IgG/IgM immune responses and clinical parameters(named COVID-ONE-hi).COVID-ONE-hi is based on the data that contain the IgG/IgM responses to 24 full-length/truncated proteins corresponding to 20 of 28 known SARS-CoV-2 proteins and 199 spike protein peptides against 2360 serum samples collected from 783 COVID-19 patients.In addition,96 clinical parameters for the 2360 serum samples and basic information for the 783 patients are integrated into the database.Furthermore,COVID-ONE-hi provides a dashboard for defining samples and a one-click analysis pipeline for a single group or paired groups.A set of samples of interest is easily defined by adjusting the scale bars of a variety of parameters.After the"START"button is clicked,one can readily obtain a comprehensive analysis report for further interpretation.COVID-ONE-hi is freely available at www.COVID-ONE.cn.