Aim To evaluate the right atrial function by two-dimensional speckle tracking imaging(2D-STI)combined with real-time three-dimensional echocardiography(RT-3DE)in patients with triple vessel coronary artery disease(TVCAD)without myocardial infarction.Methods Fifty-six patients with TVCAD without myocardial infarc-tion were selected and divided into two groups according to the results of coronary angiography:28 cases with a stenosis rate of 50％～75％and 28 cases with a stenosis rate of ≥75％.In addition,30 healthy volunteers were screened as control group.RT-3DE was performed to obtain the parameters of right atrial volume(RAVmax,RAVmin and RAVp)and then calculated right atrial passive ejection fraction(RAPEF)and right atrial active ejection fraction(RAAEF),and the maxi-mum of right atrial volume index(RAVImax).2D-STI was applied to measure right atrium strain rates during systole,ear-ly diastole and late diastole(RASRs,RASRe and RASRa).Correlation between 2D-STI parameters and N-terminal pro-brain natriuretic peptide(NT-proBNP),Gensini scores were analyzed by Pearson analysis.ROC curve analysis was used to evaluate the diagnostic value of 2D-STI,RT-3DE,and their combined use for right atrial function in TVCAD patients without myocardial infarction.Results Compared with control group,RAPEF and RASRe reduced in stenosis rate of 50％～75％group,while RAAEF and RASRa increased(all P＜0.05).Compared with control group and stenosis rate of 50％～75％group,RAPEF,RASRs,RASRe and RASRa decreased,while RAVmax,RAVmin,RAVp,RAVImax and RAAEF increased in stenosis rate of ≥75％group(all P＜0.05).There was a significant correlation between 2D-STI pa-rameters and NT-proBNP and Gensini scores.The area under the curve of right atrial function in TVCAD patients without myocardial infarction was 0.9048,0.8917 and 0.9564 for 2D-STI,RT-3DE and their combined use,respectively.The diagnostic efficacy of the two methods was significantly higher when used in combination than when used alone,and 2D-STI was superior to RT-3DE.Conclusion When evaluating the right atrial function of TVCAD patients without myocardial infarction,the diagnostic efficacy of 2D-STI combined with RT-3DE is higher than that of using it alone,and 2D-STI is su-perior to RT-3DE.

Aim To evaluate the right atrial function by two-dimensional speckle tracking imaging(2D-STI)combined with real-time three-dimensional echocardiography(RT-3DE)in patients with triple vessel coronary artery disease(TVCAD)without myocardial infarction.Methods Fifty-six patients with TVCAD without myocardial infarc-tion were selected and divided into two groups according to the results of coronary angiography:28 cases with a stenosis rate of 50％～75％and 28 cases with a stenosis rate of ≥75％.In addition,30 healthy volunteers were screened as control group.RT-3DE was performed to obtain the parameters of right atrial volume(RAVmax,RAVmin and RAVp)and then calculated right atrial passive ejection fraction(RAPEF)and right atrial active ejection fraction(RAAEF),and the maxi-mum of right atrial volume index(RAVImax).2D-STI was applied to measure right atrium strain rates during systole,ear-ly diastole and late diastole(RASRs,RASRe and RASRa).Correlation between 2D-STI parameters and N-terminal pro-brain natriuretic peptide(NT-proBNP),Gensini scores were analyzed by Pearson analysis.ROC curve analysis was used to evaluate the diagnostic value of 2D-STI,RT-3DE,and their combined use for right atrial function in TVCAD patients without myocardial infarction.Results Compared with control group,RAPEF and RASRe reduced in stenosis rate of 50％～75％group,while RAAEF and RASRa increased(all P＜0.05).Compared with control group and stenosis rate of 50％～75％group,RAPEF,RASRs,RASRe and RASRa decreased,while RAVmax,RAVmin,RAVp,RAVImax and RAAEF increased in stenosis rate of ≥75％group(all P＜0.05).There was a significant correlation between 2D-STI pa-rameters and NT-proBNP and Gensini scores.The area under the curve of right atrial function in TVCAD patients without myocardial infarction was 0.9048,0.8917 and 0.9564 for 2D-STI,RT-3DE and their combined use,respectively.The diagnostic efficacy of the two methods was significantly higher when used in combination than when used alone,and 2D-STI was superior to RT-3DE.Conclusion When evaluating the right atrial function of TVCAD patients without myocardial infarction,the diagnostic efficacy of 2D-STI combined with RT-3DE is higher than that of using it alone,and 2D-STI is su-perior to RT-3DE.

Objective This study aimed to explore the prognostic value of 18F-FDG PET/CT Metabolic and Heterogeneity Parameters Combined with Clinical Features Before Definitive Chemoradiotherapy(D-CRT)in predicting the prognosis of esophageal squamous cell carcinoma(ESCC)Patients.Methods A retrospective analysis was conducted on clinical data from 106 patients with ESCC who received D-CRT at the first affiliated Hospital of University of Science and Technology of China between January 2017 and December 2021.All patients underwent 18F-FDG PET/CT examination before the treatment.The primary tumor′s metabolic and heterogeneity parameters were obtained through data processing.All patients were followed up for overall survival.The Kaplan-Meier method and Cox proportional hazards models were used to analyze the association between clinical features,tumor metabo-lism and heterogeneity parameters and patient prognosis.Results The 1-and 1.5-year overall survival rates of all patients were 77.4%and 51.9%.The median survival time was 20 months.Univariate analysis showed that N stage,M stage,metabolic tumor volume,total lesion glycolysis,heterogeneity index-2(HI-2),and coefficient of variation with a threshold of 40%maximum standard uptake value(CV40%)were correlated with the prognosis of ESCC(all P<0.05).Multivariate analysis showed that N stage and CV40%were independent predictors of prognosis in patients with ESCC(P = 0.039 and P<0.001,respectively).Conclusion N stage and tumor metabolic heterogeneity parameter CV40%,which offering a degree of predictive value,are closely related to the prognosis of patients with ESCC treated with D-CRT.

【Objective】 To investigate the situation of carbapenem-resistant Enterobacteriaceae(CRE) colonization in patients undergoing haploidentical hematopoietic stem cell transplantation (haplo-HSCT). 【Methods】 A total of 241 consecutive patients who underwent haplo-HSCT in the First Affiliated Hospital of Soochow University from June 1, 2021 to June 1, 2022 were enrolled. Anal swab screening was performed within 48 hours of admission and blood cultures were taken when the patient developed fever. Univariate and multivariate analysis were used to analyze the colonization rate, distribution, risk factors and the correlation between CRE colonization and post-transplant bloodstream infection(BSI). 【Results】 Among 241 patients with haplo-HSCT, there were 90 cases in CRE colonization positive group, with a colonization rate of 37.3% (90/241). Multivariate logistic regression analysis showed that sex (OR 2.42, 95% CI 1.38-4.22, P<0.05) and history of infection within 30 days before transplantation (OR 3.37, 95% CI 1.59-7.17, P<0.05) may be independent risk factors for CRE intestinal colonization. Of the 95 CRE strains, the top five species were carbapenem-resistant Klebsiella pneumoniae (38/95, 40.0%), carbapenem-resistant Escherichia coli (29/95, 30.5%), carbapenem-resistant Enterobacter cloacae (13/95, 13.6%), carbapenem-resistant Klebsiella acidophilus (6/95, 6.3%) and carbapenem-resistant Proteus mirabilis (3/95, 3.1%). The incidence of post-transplant BSI was 12.0% (29/241) in the CRE-colonized group and 3.3% (8/241) in the non-colonized group. In the colonization group, 100% of the pathogens of BSI were identical with those of CRE colonization. 【Conclusion】 Bacterial culture of anal swab during haplo-HSCT is helpful for detection of CRE colonization in intestinal tract, which provides some clinical basis for active monitoring of key flora, prevention and control of infection.

Objective: To investigate the level of maternal and infant health literacy and its influencing factors among lying-in women, so as to provide insights into formulating maternal and infant health education and promotion strategies. Methods: Lying-in women were sampled from Children's Hospital of Shanxi using a cluster sampling method from March to September 2022. Demographic characteristics, maternal and infant health literacy, and health education demands were collected through a questionnaire survey. Factors affecting maternal and infant health literacy among lying-in women were identified using a multivariable logistic regression model. Results: A total of 1 099 questionnaires were allocated, and 1 059 valid questionnaires were recovered, with an effective rate of 96.36%. Participants had a mean age of (30.93±4.01) years, 930 urban residents (87.82%), and 706 pluripara (66.67%). The overall prevalence of maternal and infant health literacy was 35.51% among lying-in women, and the prevalence rates of basic knowledge and concept, healthy lifestyles and behaviors and basic skills were 47.69%, 83.10% and 38.81%, respectively. Multivariable logistic regression analysis showed that educational level (diploma or undergraduate degree, OR=3.916, 95%CI: 1.250-9.031; master degree and above, OR=4.557, 95%CI: 1.498-11.460), occupation (company employees, OR=2.701, 95%CI: 1.385-5.268; medical staff, OR=2.981, 95%CI: 1.289-6.893), pluripara (OR=5.649, 95%CI: 3.919-8.142), participating in health education activities (OR=2.332, 95%CI: 1.524-3.570), and participating in schools for pregnant women (OR=2.252, 95%CI: 1.541-3.291) were promoting factors for maternal and infant health literacy; while gestational hypertension (OR=0.255, 95%CI: 0.133-0.488) and gestational diabetes (OR=0.318, 95%CI: 0.211-0.478) were inhibiting factors for maternal and infant health literacy. Most participants acquired health knowledge through online media (62.42%), and hoped to participate in health education activities through online media publicity (68.18%). Conclusions The maternal and infant health literacy level of lying-in women in this survey is associated with education, occupation, parturition frequency, participation in health education activities, participation in schools for pregnant women, gestational hypertension and gestational diabetes.

Understanding the regulatory networks for germ cell fate specification is necessary to developing strategies for improving the efficiency of germ cell production in vitro. In this study, we developed a coupled screening strategy that took advantage of an arrayed bi-molecular fluorescence complementation (BiFC) platform for protein-protein interaction screens and epiblast-like cell (EpiLC)-induction assays using reporter mouse embryonic stem cells (mESCs). Investigation of candidate interaction partners of core human pluripotent factors OCT4, NANOG, KLF4 and SOX2 in EpiLC differentiation assays identified novel primordial germ cell (PGC)-inducing factors including BEN-domain (BEND/Bend) family members. Through RNA-seq, ChIP-seq, and ATAC-seq analyses, we showed that Bend5 worked together with Bend4 and helped mark chromatin boundaries to promote EpiLC induction in vitro. Our findings suggest that BEND/Bend proteins represent a new family of transcriptional modulators and chromatin boundary factors that participate in gene expression regulation during early germline development.
Animals ; Cell Differentiation/genetics* ; Chromatin/metabolism* ; Embryonic Stem Cells ; Germ Cells/metabolism* ; Germ Layers/metabolism* ; Mice

Adenine ; Animals ; Gene Editing ; Mice ; Zygote ; metabolism

OBJECTIVE:To establish a method for simultaneous determination of ephedrine hydrochloride,nitrofural and di-phenhydramine hydrochloride in Compound diphenhydramine nasal drop. METHODS:RP-HPLC method was adopted. The determi-nation was performed on Inertsil ODS-3 C18 column with mobile phase consisted of 0.05 mol/L potassium dihydrogen phosphate buf-fer(pH 7.0)-acetonitrile(gradient elution)with flow rate of 1.0 mL/min. The detection wavelength was set at 256 nm,and the col-umn temperature was 35 ℃. The sample size was 20 μL. RESULTS:The concentrations of phedrine hydrochloride,nitrofural and diphenhydramine hydrochloride ranged 122.1-366.3 μg/mL(r=0.9999),5.2-15.5 μg/mL(r=0.9998)and 31.5-94.5 μg/mL(r=0.9994),respectively. The limits of quantitation were 2.442,0.010,2.520 μg/mL,and the limits of detection were 0.810,0.003, 0.830 μg/mL,respectively. RSDs of precision,stability and reproducibility tests were lower than 1.0%. The recoveries of them were 99.2%-101.7%(RSD=0.9%,n=9),96.4%-102.0%%(RSD=1.7%,n=9),100.2%-101.9%(RSD=0.4%,n=9),respec-tively. CONCLUSIONS:The method is simple,accurate and reproducible,and can be used for simultaneous determination of ephedrine hydrochloride,nitrofural and diphenhydramine hydrochloride in Compound diphenhydramine nasal drop.

β-Thalassemia is a global health issue, caused by mutations in the HBB gene. Among these mutations, HBB -28 (A>G) mutations is one of the three most common mutations in China and Southeast Asia patients with β-thalassemia. Correcting this mutation in human embryos may prevent the disease being passed onto future generations and cure anemia. Here we report the first study using base editor (BE) system to correct disease mutant in human embryos. Firstly, we produced a 293T cell line with an exogenous HBB -28 (A>G) mutant fragment for gRNAs and targeting efficiency evaluation. Then we collected primary skin fibroblast cells from a β-thalassemia patient with HBB -28 (A>G) homozygous mutation. Data showed that base editor could precisely correct HBB -28 (A>G) mutation in the patient's primary cells. To model homozygous mutation disease embryos, we constructed nuclear transfer embryos by fusing the lymphocyte or skin fibroblast cells with enucleated in vitro matured (IVM) oocytes. Notably, the gene correction efficiency was over 23.0% in these embryos by base editor. Although these embryos were still mosaic, the percentage of repaired blastomeres was over 20.0%. In addition, we found that base editor variants, with narrowed deamination window, could promote G-to-A conversion at HBB -28 site precisely in human embryos. Collectively, this study demonstrated the feasibility of curing genetic disease in human somatic cells and embryos by base editor system.
APOBEC-1 Deaminase ; genetics ; metabolism ; Base Sequence ; Blastomeres ; cytology ; metabolism ; CRISPR-Cas Systems ; Embryo, Mammalian ; metabolism ; pathology ; Female ; Fibroblasts ; metabolism ; pathology ; Gene Editing ; methods ; Gene Expression ; HEK293 Cells ; Heterozygote ; Homozygote ; Humans ; Point Mutation ; Primary Cell Culture ; Promoter Regions, Genetic ; Sequence Analysis, DNA ; beta-Globins ; genetics ; metabolism ; beta-Thalassemia ; genetics ; metabolism ; pathology ; therapy

Targeted point mutagenesis through homologous recombination has been widely used in genetic studies and holds considerable promise for repairing disease-causing mutations in patients. However, problems such as mosaicism and low mutagenesis efficiency continue to pose challenges to clinical application of such approaches. Recently, a base editor (BE) system built on cytidine (C) deaminase and CRISPR/Cas9 technology was developed as an alternative method for targeted point mutagenesis in plant, yeast, and human cells. Base editors convert C in the deamination window to thymidine (T) efficiently, however, it remains unclear whether targeted base editing in mouse embryos is feasible. In this report, we generated a modified high-fidelity version of base editor 2 (HF2-BE2), and investigated its base editing efficacy in mouse embryos. We found that HF2-BE2 could convert C to T efficiently, with up to 100% biallelic mutation efficiency in mouse embryos. Unlike BE3, HF2-BE2 could convert C to T on both the target and non-target strand, expanding the editing scope of base editors. Surprisingly, we found HF2-BE2 could also deaminate C that was proximal to the gRNA-binding region. Taken together, our work demonstrates the feasibility of generating point mutations in mouse by base editing, and underscores the need to carefully optimize base editing systems in order to eliminate proximal-site deamination.
APOBEC-1 Deaminase ; genetics ; metabolism ; Animals ; Bacterial Proteins ; genetics ; metabolism ; Base Sequence ; CRISPR-Associated Protein 9 ; CRISPR-Cas Systems ; Cytidine ; genetics ; metabolism ; Embryo Transfer ; Embryo, Mammalian ; Endonucleases ; genetics ; metabolism ; Gene Editing ; methods ; HEK293 Cells ; High-Throughput Nucleotide Sequencing ; Humans ; Mice ; Mice, Inbred C57BL ; Microinjections ; Plasmids ; chemistry ; metabolism ; Point Mutation ; RNA, Guide ; genetics ; metabolism ; Thymidine ; genetics ; metabolism ; Zygote ; growth & development ; metabolism ; transplantation