Objective:To investigate the clinical characteristics of a family with maturity-onset diabetes of the young type 3(MODY3) and assess its association with the novel HNF1A-c.47T>A variant.Methods:A genetic pedigree of the MODY3 family was constructed, and clinical data were collected. Whole-exome sequencing combined with Sanger sequencing was used, followed for familial co-segregation analysis. Bioinformatics tools, including multiple sequence alignment–based conservation analysis and protein structural prediction, were conducted to validate the association between the novel HNF1A-c.47T>A variant and MODY3.Results:Seven MODY3 patients were diagnosed in this family, all harboring the HNF1A-c.47T>A heterozygous variant. AlphaFold2 protein structure prediction indicated that the HNF1A-c.47T>A variant altered the conformation of the first pair of α-helices within the protein dimerization domain.Conclusion:Based on co-segregation analysis, sequence conservation assessment, protein structure prediction, and classification based on American College of Medical Genetics and Genomics(ACMG) Guidelines, the HNF1A-c.47T>A variant was determined to be pathogenic for MODY3. This study reports this novel pathogenic variant, expanding the mutational spectrum of MODY3. By revealing its disruptive effect on the protein dimerization domain, the findings provide a potential molecular basis for the diagnosis and management of patients carrying similar variants.

Objective:To investigate the clinical characteristics of a family with maturity-onset diabetes of the young type 3(MODY3) and assess its association with the novel HNF1A-c.47T>A variant.Methods:A genetic pedigree of the MODY3 family was constructed, and clinical data were collected. Whole-exome sequencing combined with Sanger sequencing was used, followed for familial co-segregation analysis. Bioinformatics tools, including multiple sequence alignment–based conservation analysis and protein structural prediction, were conducted to validate the association between the novel HNF1A-c.47T>A variant and MODY3.Results:Seven MODY3 patients were diagnosed in this family, all harboring the HNF1A-c.47T>A heterozygous variant. AlphaFold2 protein structure prediction indicated that the HNF1A-c.47T>A variant altered the conformation of the first pair of α-helices within the protein dimerization domain.Conclusion:Based on co-segregation analysis, sequence conservation assessment, protein structure prediction, and classification based on American College of Medical Genetics and Genomics(ACMG) Guidelines, the HNF1A-c.47T>A variant was determined to be pathogenic for MODY3. This study reports this novel pathogenic variant, expanding the mutational spectrum of MODY3. By revealing its disruptive effect on the protein dimerization domain, the findings provide a potential molecular basis for the diagnosis and management of patients carrying similar variants.

Abstract: Objective To analysis the genetic evolution characteristics of hemagglutinin (HA) gene of influenza A(H1N1)pdm virus in Changsha City from 2016-2023, to understand the trend of the HA genetic evolution and the mutations of the amino acid. It provides a scientific basis for the prevention and control of influenza epidemics, as well as the screening of vaccines under the new situation. Methods The A(H1N1)pdm09 virus strains from Changsha City from 2016 to 2023 were isolated using SPF chicken embryos, and then the HA genes were sequenced by MiSeq of Illumina Inc. The homology of HA gene was analyzed by MegAlign of the DNASTAR, and the phylogenetic tree was constructed using the Neighbor Joining (NJ) method in the Molecular Evolutionary Genetics Analysis version 11 (MEGA11). Results The homology of the HA gene of A(H1N1)pdm virus in Changsha from 2016 to 2023 was between 94.8%-99.9%, with the HA gene homology decreasing annually. The homology between the isolated strains of A(H1N1)pdm09 in Changsha City from 2016 to 2023 and the WHO recommended vaccine strain ranged from 96.8% to 99.0%, indicating a relatively good match between the flu isolates and the recommended vaccine strain. The phylogenetic tree of the HA gene of the A(H1N1)pdm09 influenza virus in Changsha City showed that the HA gene evolved into several different branches within the 6B branch, and it had currently evolved to 6B.1A.5a.2a branch. Constant mutations had occurred at the amino acid sites of the four antigenic determinant clusters of HA protein. Currently, amino acid mutations had occurred at 15 antigenic sites within the four antigenic determinant clusters, and the newly emerged A186T antigen mutant site in the isolates from 2023 was worth recent notice. The receptor-binding sites are relatively conserved in loop 130, minor amino acid mutations occurred in loop 220, whether the amino acid mutation site in loop 190 is becoming more stable needs to be further monitored. Taking A/California/07/2009 (CY121680) as the reference strain, most of the A(H1N1) pdm09 isolates in Changsha was increased 162 NQTY glycosylation site and was decreased 276 NTTC glycosylation site, and the glycosylation mutations at these two sites have become more stable recently. Conclusions The HA genes of influenza A(H1N1)pdm virus in Changsha are constantly evolving and mutating, suggesting influenza surveillance should be strengthened continuously.

Emerging SARS-CoV-2 variants have made COVID-19 convalescents susceptible to re-infection and have raised concern about the efficacy of inactivated vaccination in neutralization against emerging variants and antigen-specific B cell response. To this end, a study on a long-term cohort of 208 participants who have recovered from COVID-19 was conducted, and the participants were followed up at 3.3 (Visit 1), 9.2 (Visit 2), and 18.5 (Visit 3) months after SARS-CoV-2 infection. They were classified into three groups (no-vaccination (n = 54), one-dose (n = 62), and two-dose (n = 92) groups) on the basis of the administration of inactivated vaccination. The neutralizing antibody (NAb) titers against the wild-type virus continued to decrease in the no-vaccination group, but they rose significantly in the one-dose and two-dose groups, with the highest NAb titers being observed in the two-dose group at Visit 3. The NAb titers against the Delta variant for the no-vaccination, one-dose, and two-dose groups decreased by 3.3, 1.9, and 2.3 folds relative to the wild-type virus, respectively, and those against the Omicron variant decreased by 7.0, 4.0, and 3.8 folds, respectively. Similarly, the responses of SARS-CoV-2 RBD-specific B cells and memory B cells were boosted by the second vaccine dose. Results showed that the convalescents benefited from the administration of the inactivated vaccine (one or two doses), which enhanced neutralization against highly mutated SARS-CoV-2 variants and memory B cell responses. Two doses of inactivated vaccine among COVID-19 convalescents are therefore recommended for the prevention of the COVID-19 pandemic, and vaccination guidelines and policies need to be updated.

Objective:To investigate clinical efficacy of curved fenestration and drainage procedure for the treatment of nail root abscess.Methods:From June 2018 to October 2020, 72 patients with nail root abscess were included in Department of Dermatology, Henan Armed Police Corps Hospital. According to the size, location and severity of the abscess, minimally invasive curved fenestration and drainage procedure was performed under nerve block anesthesia to reduce the pressure and drain the pus. Dressing change was strengthened after surgery, and wound healing was monitored.Results:Among the 72 patients, there were 37 males and 35 females, and their ages varied from 39 to 80 years (average: 63 years) . They all received curved fenestration and drainage procedure. Fifteen days after surgery, 66 cases were cured, 6 obtained marked improvement, and the response rate was 100%. Lesions did not completely subside in 1 patient due to poor blood glucose control and small exposure area at the fenestration site, while the condition of other patients was effectively controlled. Telephone follow-up was conducted 3 months after surgery, and no obvious nail defects or deformed appearance was observed in any of the cases.Conclusion:Curved fenestration and drainage procedure is a simple approach for nail root abscess, with satisfactory efficacy.

OBJECTIVE: To determine the types and frequency of deafness-related variants among 7875 newborns from Dongying area of Shandong Province. METHODS: One hundred loci of 18 common deafness genes were subjected to semiconductor sequencing. Variant site, frequency and distribution of the variants were analyzed. RESULTS: In total 552 deafness gene variants were detected among the 7875 newborns, which yielded a detection rate of 7.01%. Among these, common variant sites for GJB2, SLC26A4 and GJB3 genes were c.235delC, IVS7-2A>G and c.538C>T, respectively. The variant frequencies of matrilinear inheritance deafness genes MT-CO1, MT-RNR1, MT-TL1 and MT-TS1 were 0.38%, 0.25%, 0.1% and 0.01%, respectively. Four newborns were diagnosed with deafness, among which one had unilateral hearing loss. Analysis of the proportions of neonatal deafness-related variants in five counties of Dongying showed that the highest variant rate for the SLC26A4 gene compared with GJB2 was in Lijin county (51.76% vs. 40%), while the lowest was in Hekou county (30.77% vs. 56.41%). CONCLUSION The carrier rate of deafness-related variants in Dongying area is higher than other regions of China, which may be attributed to the increased types and variant sites covered by the semiconductor sequencing method compared with the chip method and time-of-flight mass spectrometry. Due to geographical and population aggregation factors, the proportion of deafness variants in the five counties of Dongying differed significantly. Above results may provide a guide for the prevention of congenital deafness in Dongying area.

Objective To evaluate the efficacy and safety of early endoscopic retrograde cholangiopancreatography (ERCP) with endoscopic sphincterotomy (EST) in patients of acute biliary pancreatitis (ABP).Methods Databases including PubMed,EMBASE,Cochrane library,CBM,CNKI,WanFang data and VIP data were searched with " Endoscopic retrograde cholangiopancreatography" "Endoscopic sphincterotomy" "ERCP" "Pancreatitis" "Biliary pancreatitis" resection up to September 2017.Randomized controlled trails (RCTs) conternming the comparison of ERCP with EST versus conservative management in ABP patients were enrolled in the study.Two reviewers independently screened literature,extracted data,and assess the risk of bias of the included studies.The Meta-analysis was conducted by RevMan 5.3 software.Results A total of 10 RCTs involving 1 752 cases were included in the Metaanalysis.The results of Meta-analysis showed that compared with the control group,early ERCP with EST reduced the systemic complication rate of ABP (RR =0.66;95％ CI:0.47-0.93;P ＜ 0.05).However,there were no significant differences in overall mortality,local complication rate,and ERCP related complication rate in ABP between early and selected ERCP with EST treat (P ＞ 0.05).Subgroup analyses indicated that early ERCP with EST therapy reduced the mortality of severe acute biliary pancreatitis (SABP),ABP with biliary obstruction and within 24 hours of admission (RR =0.48,0.35,0.25;95％ CI:0.24-0.96,0.17-0.74,0.09-0.73;P ＜ 0.05);decreased the local and systemic complication rate of SABP,ABP with biliary obstruction (RR =0.56,0.54,0.51,0.51;95％ CI:0.37-0.86,0.33-0.91,0.32-0.81,0.32-0.80;P ＜ 0.05);reduced the local and systemic complication rate of SABP (RR =0.42,0.47;95％ CI:0.25-0.70,0.25-0.87;P ＜0.05) and shortened the hospital stay of SABP (MD =-11.22 d;95％ CI:-16.09--6.36;P ＜ 0.01).However,there were no significant differences of overall complication rate in ABP without biliary obstruction and hospital stay in MABP.Conclusion Early ERCP with EST therapy appears to be safe and effective for ABP patients.

Objective To investigate the relationship between the marrow edema and general clinical index,quadriceps muscle area,and the meniscus grade of knee osteoarthritis(OA).Methods 72 patients were collected with knee OA in our hospital, underwent X-ray and routine MRI examination of knee, and the same X-ray and MRI were reviewed at 12 months later in different time point.The K-L grading, bone marrow edema score, meniscal grading and VAS score of each knee joint were evaluated.The t-test and Rank-sum test were used to compare the two groups of general data, Spearman was used to perform bivariate correlation analysis.Results The age and VAS score of bone marrow edema group at the initial follow-up were significantly lower than those without edema group(P<0.05),the degree of marrow edema was moderately correlated with age and VAS score, and was not significantly correlated with other indexes.12 months later, BMI and the area of quadriceps femoris in the group with marrow edema were different from those in the group without bone marrow edema(P<0.05), the degree of marrow edema was moderately correlated with age, quadriceps area and VAS.Conclusion The range of marrow edema was related to age, quadriceps area, BMI index and VAS score in MRI.The MRI measurement could reflect the progression of knee OA more than that of X-ray.It also revealed some factors related to the progression of knee OA.

ABSTRACT:Objective To compare the prognostic value of cystatin-C (Cys-C)and creatinine (Cr)in chronic heart failure (CHF)in old people.Methods We recruited 183 old patients (>75 years)diagnosed with CHF hospitalized at the Department of Cardiology and the Department of Geriatrics of our hospital from 2010 to 2012. Venous blood was withdrawn to detect the expressions of Cys-C and Cr.After three-year follow-up,the patients’ three-year survival was recorded.Logistic regression model was used to examine the relationship of Cys-C,Cr and other risk factors with the CHF patients’mortality.ROC curve was used to compare the prognostic value of Cys-C and Cr in CHF in old people and statistical method was adopted to analyze the combined use of Cys-C and Cr for determining their value in evaluating CHF prognosis.Results At the end of the follow-up,74 (40.44%)patients died.Serum cys-C and Cr levels of the patients in death group increased compared with those in survival group (P<0.05).Multivariate logistic regression showed that age (OR=1.11,95% CI=1.04-1.19),SBP (OR=1.06,95%CI=1.01-1.10),LVEF (OR=0.89,95% CI=0.82-0.95),BNP (OR=4.74,95% CI=1.77-12.69), creatinine (OR=2.04,95% CI=1.03-4.08),and Cys-C (OR=2.97,95% CI=1.44-6.12)were the independent risk factors for the prognosis of CHF.ROC analysis showed that Cys-C was superior to creatinine in AUC value (0.71 vs.0.65;95% CI,0.64-0.78;95% CI,0.58-0.72)(P<0.001).The AUC value of Cys-C and Cr in combination was 0.73 (95% CI,0.66-0.79).Conclusion Cys-C is a stronger predictor of the prognosis of CHF patients than creatinine and the combination of the two can increase the sensitivity and specificity in evaluating the prognosis of patients with CHF.

Objective:to apply Fuzhengkangai AIDS particles combined therapy with effective antiretroviral therapy (HAART) at the beginning of the HIV/AIDS (human immunodeficiency virus/acquired immunodeficiency syndrome) patients,observe its clinical curative effect and improve the related adverse reactions.Methods:a multicenter,randomized,double-blind,placebo-controlled clinical research method,divided into experimental group and the control group (n =57),experimental group to "Fuzhengkangai particles" joint efficient antiretroviral therapy (HAART) antiviral treatment,control group to "Fuzhengkangai particles" placebo (5％ low dose) joint efficient antiretroviral therapy (HAART) antiviral treatment,treatment for 3 months.Two groups of patients with simultaneous liver and kidney function,blood routine,CD4 + T lymphocyte count,the observation of TCM symptoms and signs,survival quality of integral.Results:after 12 weeks of treatment,the control group and experimental group,the experimental group significantly elevated levels of peripheral blood RBC,lower levels of CR,reduce the signs and symptoms (total score,fatigue,stay,and spontaneous perspiration)integral,higher levels of CD4 + T lymphocyte count and survival quality score,the difference had statistical significance (p ＜ 0.05).Conclusion:Fuzhengkangai particles joint efficient antiretroviral therapy (HAART) antiviral treatment,can improve HAART after initial treatment of the patient's clinical symptoms,blood toxicity,the quality of survival,reduce the antiviral treatment of adverse reactions,combination drug alone can significantly increase the CD4 + T lymphocytes,so as to improve clinical curative effect.