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Background: Carbapenem-resistant hypervirulent Klebsiella pneumoniae (CR-hvKP) is gradually becoming the dominant nosocomial pathogens in the healthcare setting. Methods: A retrospective study was conducted on patients with CR-KP from July 2021 to May 2022 in a teaching hospital. We identified bacterial isolates, collected the clinical data, and performed antimicrobial susceptibility testing, hypermucoviscosity string test, antimicrobial and virulence-associated genotype, as well as multi-locus sequence typing. CR-hvKP was defined as the presence of some combination of rmpA and/or rmpA2 with iucA, iroB, or peg-344. SPSS was used for data analysis. Univariate logistic regression analyses were used for risk factor and all statistically significant variables were included in the multivariate model. Statistical significance was taken to be P < 0.05. Results: A total of 69 non-duplicated CR-KP isolates were collected, 27 of which were CR-hvKP. Out of the 69 CR-KP strains under investigation, they were distributed across 14 distinct sequence types (STs), wherein ST11 exhibited the highest prevalence, constituting 65.2% (45/69) of the overall isolates. The principal carbapenemase genes identified encompassed blakpc−2, blaNDM−1, and blaOXA−48, with blakpc−2 prevailing as the predominant type, accounting for 73.9% (51/69). A total of 69 CR-KP strains showed high resistance to common clinical antibiotics, with the exception of ceftazidime/avibactam. The ST11 (P = 0.040), ST65 (P = 0.030) and blakpc−2 ST11 clones (P = 0.010) were found to be highly related to hvKp. Regarding the host, tracheal intubation (P = 0.008), intracranial infection (P = 0.020) and neutrophil count (P = 0.049) were significantly higher in the patients with CR-hvKP. Multivariate analysis showed tracheal intubation to be an independent risk factor for CR-hvKP infection (P = 0.030, OR = 4.131). According to the clinical data we collected, tracheal intubation was performed mainly in the elderly with severe underlying diseases, which implied that CR-hvKP has become prevalent among elderly patients with comorbidities. Conclusions: The prevalence of CR-hvKP may be higher than expected in the healthcare setting. CR-hvKP is gradually becoming the dominant nosocomial pathogen, and its prevalence and treatment will be a major challenge. It is essential to enhance clinical awareness and management of CR-hvKP infection. [ABSTRACT FROM AUTHOR]

Background: As an extension of electron tomography (ET), serial section electron tomography (serial section ET) aims to align the tomographic images of multiple thick tissue sections together, to break through the volume limitation of the single section and preserve the sub-nanoscale voxel size. It could be applied to reconstruct the intact synapse, which expands about one micrometer and contains nanoscale vesicles. However, there are several drawbacks of the existing serial section ET methods. First, locating and imaging regions of interest (ROIs) in serial sections during the shooting process is time-consuming. Second, the alignment of ET volumes is difficult due to the missing information caused by section cutting and imaging. Here we report a workflow to simplify the acquisition of ROIs in serial sections, automatically align the volume of serial section ET, and semi-automatically reconstruct the target synaptic structure. Results: We propose an intelligent workflow to reconstruct the intact synapse with sub-nanometer voxel size. Our workflow includes rapid localization of ROIs in serial sections, automatic alignment, restoration, assembly of serial ET volumes, and semi-automatic target structure segmentation. For the localization and acquisition of ROIs in serial sections, we use affine transformations to calculate their approximate position based on their relative location in orderly placed sections. For the alignment of consecutive ET volumes with significantly distinct appearances, we use multi-scale image feature matching and the elastic with belief propagation (BP-Elastic) algorithm to align them from coarse to fine. For the restoration of the missing information in ET, we first estimate the number of lost images based on the pixel changes of adjacent volumes after alignment. Then, we present a missing information generation network that is appropriate for small-sample of ET volume using pre-training interpolation network and distillation learning. And we use it to generate the missing information to achieve the whole volume reconstruction. For the reconstruction of synaptic ultrastructures, we use a 3D neural network to obtain them quickly. In summary, our workflow can quickly locate and acquire ROIs in serial sections, automatically align, restore, assemble serial sections, and obtain the complete segmentation result of the target structure with minimal manual manipulation. Multiple intact synapses in wild-type rat were reconstructed at a voxel size of 0.664 nm/voxel to demonstrate the effectiveness of our workflow. Conclusions: Our workflow contributes to obtaining intact synaptic structures at the sub-nanometer scale through serial section ET, which contains rapid ROI locating, automatic alignment, volume reconstruction, and semi-automatic synapse reconstruction. We have open-sourced the relevant code in our workflow, so it is easy to apply it to other labs and obtain complete 3D ultrastructures which size is similar to intact synapses with sub-nanometer voxel size. [ABSTRACT FROM AUTHOR]

Background: Bocaviruses are classified as a genus within the Parvoviridae family of single-stranded DNA viruses and are pathogenic in some mammalian species. Two species have been previously reported in dogs, minute virus of canines (MVC), associated with neonatal diseases and fertility disorders; and Canine bocavirus (CBoV), associated with respiratory disease. Findings: In this study using deep sequencing of enriched viral particles from the liver of a dog with severe hemorrhagic gastroenteritis, necrotizing vasculitis, granulomatous lymphadenitis and anuric renal failure, we identified and characterized a novel bocavirus we named Canine bocavirus 3 (CnBoV3). The three major ORFs of CnBoV3 (NS1, NP1 and VP1) shared less than 60% aa identity with those of other bocaviruses qualifying it as a novel species based on ICTV criteria. Inverse PCR showed the presence of concatemerized or circular forms of the genome in liver. Conclusions: We genetically characterized a bocavirus in a dog liver that is highly distinct from prior canine bocaviruses found in respiratory and fecal samples. Its role in this animal's complex disease remains to be determined. [ABSTRACT FROM AUTHOR]

Background: This study aimed to explore the incidence and influencing factors for early pregnancy loss (EPL) in infertility patients with first pregnancy undergoing in vitro fertilization (IVF) embryo transfer cycles in Jilin province, China.Methods: A retrospective study of 2709 first pregnancy embryo transfer cycles collected from January 2016 to January 2021 was performed. The cycles were divided into the EPL group (n = 411) and the live birth group (n = 2298) according to the cycle outcomes.Results: The EPL rate of the first-time pregnancies for infertility patients undergoing fresh/frozen-thaw embryo transfer cycle was 14.1%. Female patients aged 40 and older had increased odds of EPL compared to those under 35 (OR = 3.97, 95%CI: 2.80-7.55). Female patients with a body mass index (BMI) of 25 or greater were more likely to have EPLs than those in the normal BMI range (OR = 1.32, 95%CI: 1.03-1.70). The odds of EPL after frozen-thaw embryo transfer were higher than those after fresh embryo transfer (OR = 1.59, 95%CI: 1.11-2.27). A thin endometrium on the day of embryo transfer increased the odds of EPL (OR = 1.84, 95%CI: 1.01-3.33). Transferring more than two embryos had lower odds of EPL than single-embryo transfer (OR = 0.67, 95%CI: 0.50-0.90). Compared with other infertility diagnoses, tubal factor alone was associated with lower odds of EPL (OR = 0.72, 95%CI: 0.53-0.98).Conclusions: The risk factors for EPL were age 40 and older, obesity, frozen-thaw cycle, thin endometrium, and non-isolated tubal factor. [ABSTRACT FROM AUTHOR]

Purpose: Carbapenem resistant Klebsiella pneumoniae is associated with nosocomial infections and can cause high mortality, which poses great threat to human health. This study was aimed at investigating the molecular epidemiology and antimicrobial resistance profiles of carbapenem resistant Klebsiella pneumoniae isolates and providing clues for management and control of carbapenem resistant Klebsiella pneumoniae infections. Methods: A total of 2324 Klebsiella pneumoniae strains were isolated from the First Affiliated Hospital of Guangxi Medical University from June 2018 to October 2020, and 103 carbapenem resistant Klebsiella pneumoniae strains from inpatients were collected, and the specimens mainly came from the sputum, urine, secretions, and blood. The antimicrobial susceptibility tests were performed using the VITEK 2 Compact system or the Kirby–Bauer disk-diffusion method. The resistance genes were detected by polymerase chain reaction and sequencing. The homology analysis of carbapenem resistant Klebsiella pneumoniae strains was performed by multilocus sequence typing. Results: Antimicrobial susceptibility results showed that the 103 carbapenem resistant Klebsiella pneumoniae strains were resistant to most common antibiotics. Resistance genes detection showed that the carbapenem resistant Klebsiella pneumoniae isolates mainly carried metallo-beta-lactamase, and the predominant gene was NDM-1. The homology analysis found that the major ST type were ST11, follow by ST15 and ST17. Conclusion: The carbapenem resistant Klebsiella pneumoniae isolates in our study shown resistance to most common antibiotics. Of the 103 carbapenem resistant Klebsiella pneumoniae strains, 91 strains (88.35%) carried carbapenemases genes, and NDM was the predominant carbapenemase gene detected. ST11 was the major ST typing of carbapenem resistant Klebsiella pneumoniae in our hospital. Our finding may play a role in control and management of the carbapenem resistant Klebsiella pneumoniae infections and guiding clinical antibiotic therapy. In addition, metallo-beta-lactamase should be served as a key target to be monitored in carbapenem resistant Klebsiella pneumoniae infection. [ABSTRACT FROM AUTHOR]

Background: The miR-351 gene is significantly upregulated in diabetic mice with atherosclerosis. However, the mechanism by which its presence is important for the overall disease has not been elucidated. Therefore, this study will investigate the mechanism of miR-351 in the process of diabetes mellitus with atherosclerosis through miR-351 gene knockout mice. Methods: In this study, miR-351−/− C57BL/6 mice were first induced to form a type 2 diabetes mellitus model with atherosclerosis by STZ injection and a high-fat diet. Pathological tests (oil red O, HE, and Masson staining) combined with biochemical indices (TC, TG, LDL-C, HDL-C, TNF-α, hs-CRP, NO, SOD, MDA, CAT, and GSH-Px) were performed to evaluate the pathological degree of atherosclerosis in each group. Mouse aortic endothelial cells were treated with oxidized low-density lipoprotein (ox-LDL) and 30 mM glucose to establish a diabetic atherosclerosis cell model. Combined with cell oil red O staining and flow cytometry, the effects of silencing miR-351 on lipid accumulation and cell apoptosis in the diabetic atherosclerosis cell model were determined. Fluorescence in situ hybridization was used to detect the localization and transcription levels of miR-351 in cells. The target genes of miR-351 were predicted by bioinformatics and verified by dual-luciferase activity reporting. Western blotting was used to detect the expression levels of phosphorylated inosine 3-kinase regulatory subunit 1 (PIK3R1)/serine/threonine kinase 1 (Akt) and apoptosis-related proteins after transfection with integrin subunit β3 (ITGB3) small interfering ribonucleic acid (siRNA). Results: The expression of the miR-351 gene was significantly increased in the high-fat wild-type (HWT) group, and its expression was significantly decreased in the knockout mice. Silencing miR-351 effectively alleviated atherosclerosis in mice. The levels of miR-351 expression, apoptosis, lipid accumulation, and oxidative stress in ox-LDL + high glucose-induced endothelial cells were significantly increased. These phenomena were effectively inhibited in lentivirus-infected miR-351-silenced cell lines. Bioinformatics predicted that miR-351-5p could directly target the ITGB3 gene. Transfection of ITGB3 siRNA reversed the downregulation of apoptosis, decreased oil accumulation, and decreased oxidative stress levels induced by miR-351 silencing. In addition, it inhibited the activation of the PIK3R1/Akt pathway. Conclusion: Silencing miR-351 upregulates ITGB3 and activates the PIK3R1/Akt pathway, thereby exerting anti-apoptosis and protective effects on endothelial cells. [ABSTRACT FROM AUTHOR]

Background: The miR-351 gene is significantly upregulated in diabetic mice with atherosclerosis. However, the mechanism by which its presence is important for the overall disease has not been elucidated. Therefore, this study will investigate the mechanism of miR-351 in the process of diabetes mellitus with atherosclerosis through miR-351 gene knockout mice. Methods: In this study, miR-351−/− C57BL/6 mice were first induced to form a type 2 diabetes mellitus model with atherosclerosis by STZ injection and a high-fat diet. Pathological tests (oil red O, HE, and Masson staining) combined with biochemical indices (TC, TG, LDL-C, HDL-C, TNF-α, hs-CRP, NO, SOD, MDA, CAT, and GSH-Px) were performed to evaluate the pathological degree of atherosclerosis in each group. Mouse aortic endothelial cells were treated with oxidized low-density lipoprotein (ox-LDL) and 30 mM glucose to establish a diabetic atherosclerosis cell model. Combined with cell oil red O staining and flow cytometry, the effects of silencing miR-351 on lipid accumulation and cell apoptosis in the diabetic atherosclerosis cell model were determined. Fluorescence in situ hybridization was used to detect the localization and transcription levels of miR-351 in cells. The target genes of miR-351 were predicted by bioinformatics and verified by dual-luciferase activity reporting. Western blotting was used to detect the expression levels of phosphorylated inosine 3-kinase regulatory subunit 1 (PIK3R1)/serine/threonine kinase 1 (Akt) and apoptosis-related proteins after transfection with integrin subunit β3 (ITGB3) small interfering ribonucleic acid (siRNA). Results: The expression of the miR-351 gene was significantly increased in the high-fat wild-type (HWT) group, and its expression was significantly decreased in the knockout mice. Silencing miR-351 effectively alleviated atherosclerosis in mice. The levels of miR-351 expression, apoptosis, lipid accumulation, and oxidative stress in ox-LDL + high glucose-induced endothelial cells were significantly increased. These phenomena were effectively inhibited in lentivirus-infected miR-351-silenced cell lines. Bioinformatics predicted that miR-351-5p could directly target the ITGB3 gene. Transfection of ITGB3 siRNA reversed the downregulation of apoptosis, decreased oil accumulation, and decreased oxidative stress levels induced by miR-351 silencing. In addition, it inhibited the activation of the PIK3R1/Akt pathway. Conclusion: Silencing miR-351 upregulates ITGB3 and activates the PIK3R1/Akt pathway, thereby exerting anti-apoptosis and protective effects on endothelial cells. [ABSTRACT FROM AUTHOR]

Background: Our epidemiological study showed that the intestinal flora of Uygur T2DM patients differed from that of normal glucose-tolerant people. However, whether the Uygur T2DM fecal microbiota transplantation could reproduce the glucose metabolism disorder and the mechanism behind has not been reported. This study was designed to explore whether Uygur T2DM fecal microbiota transplantation could reproduce the glucose metabolism disorder and its mechanism. Methods: The normal diet and high fat diet group consisted of C57BL/6 mice orally administered 0.2 mL sterile normal saline. For the MT (microbiota transplantation) intervention groups, C57BL/6 mice received oral 0.2 mL faecal microorganisms from Uygur T2DM. All mice were treated daily for 8 weeks and Blood glucose levels of mice were detected. Mice faecal DNA samples were sequenced and quantified using 16S rDNA gene sequencing. Then we detected the ability of the intestinal flora to metabolize bile acids (BAs) through co-culture of fecal bacteria and BAs. BA levels in plasma were determined by UPLC-MS. Further BA receptors and glucagon-like peptide-1 (GLP-1) expression levels were determined with RT-q PCR and western blotting. Results: MT impaired insulin and oral glucose tolerance. Deoxycholic acid increased and tauro-β-muricholic acid and the non-12-OH BA:12-OH BA ratio decreased in plasma. MT improved the ability of intestinal flora to produce deoxycholic acid. Besides, the vitamin D receptor in the liver and ileum and GLP-1 in the ileum decreased significantly. Conclusions: Uygur T2DM fecal microbiota transplantation disrupts glucose metabolism by changing the ability of intestinal flora to metabolize BAs and the BAs/GLP-1 pathway. [ABSTRACT FROM AUTHOR]

Background: To compare the accuracy of different obesity indexes, including waist circumference (WC), weight-to-height ratio (WHtR), body mass index (BMI), and lipid accumulation product (LAP), in predicting metabolic syndrome (MetS) and to estimate the optimal cutoffs of these indexes in a rural Chinese adult population. Methods: This prospective cohort involved 8468 participants who were followed up for 6 years. MetS was defined by the International Diabetes Federation, American Heart Association, and National Heart, Lung, and Blood Institute criteria. The power of the 4 indexes for predicting MetS was estimated by receiver operating characteristic (ROC) curve analysis and optimal cutoffs were determined by the maximum of Youden's index. Results: As compared with WHtR, BMI, and LAP, WC had the largest area under the ROC curve (AUC) for predicting MetS after adjusting for age, smoking, drinking, physical activity, and education level. The AUCs (95% CIs) for WC, WHtR, BMI, and LAP for men and women were 0.862 (0.851–0.873) and 0.806 (0.794–0.817), 0.832 (0.820–0.843) and 0.789 (0.777–0.801), 0.824 (0.812–0.835) and 0.790 (0.778–0.802), and 0.798 (0.785–0.810) and 0.771 (0.759–0.784), respectively. The optimal cutoffs of WC for men and women were 83.30 and 76.80 cm. Those of WHtR, BMI, and LAP were approximately 0.51 and 0.50, 23.90 and 23.00 kg/m2, and 19.23 and 20.48 cm.mmol/L, respectively. Conclusions: WC as a preferred index over WHtR, BMI, and LAP for predicting MetS in rural Chinese adults of both genders; the optimal cutoffs for men and women were 83.30 and 76.80 cm. [ABSTRACT FROM AUTHOR]

Background: The purpose of this study was to evaluate the effect of single-nucleotide polymorphisms (SNPs) of the GCKR and G6PC2 genes on risk for type 2 diabetes and the SNP-SNP and haplotype-based interactions between these genes. Methods: Subjects of this nested case-control study were selected from a prospective cohort residing in the rural area of Luoyang city in China. Cases ( n = 538) were individually matched with controls. Six SNPs in the GCKR and G6PC2 genes were selected and genotyped using an SNPscan™ kit. Stratified Cox proportional hazards regression models were used to generate odds ratios (ORs) and 95% confidence intervals (CI) for different genotype models for the risk of T2DM. Generalized multifactor dimensionality reduction (GMDR) was used to analyze the interactions between two genes with among six SNPs. The linkage disequilibrium (LD) analysis and the haplotype analysis were carried out by SHEsis online. Results: We found that the C allele of rs780094 was associated with increased risk for T2DM in Han Chinese population. However, the rs492594-C allele in G6PC2 was associated with a decreased risk of T2DM. We also found a significant SNP-SNP interaction between rs2293572 and rs492594, and the CCCCGC and CGCCCA haplotypes significantly increased the risk of T2DM, however, the CCCCCA haplotype had lower susceptibility to T2DM. Conclusion: The results suggest that the GCKR and G6PC2 genes may contribute to the risk of T2DM independently and/or in an interactive manner in the Han Chinese population. [ABSTRACT FROM AUTHOR]

Background: The prevalence of dyslipidemia continue to increase in recent decades in China, however, little is known about the recent prevalence, awareness, treatment, control, and potential risk factors of dyslipidemia in the rural areas of China. Methods: A total of 39,207 participants aged 18–79 years were recruited for the epidemiological research from the Henan Rural Cohort study. The age- and sex-adjusted means (95% confidence intervals, CI) of serum lipid levels or percentages of prevalence, awareness, treatment, and control overall and in various population subgroups were estimated and compared by multiple linear regression or logistic regression. The multivariable logistic regression model was used to explore the associations between the socio-demographic factors and the prevalence, awareness, treatment and control of dyslipidemia. Results: The age- and sex-adjusted mean levels (95%CI) of total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) were 4.76(4.75–4.77), 1.68(1.67–1.69),1.33(1.32–1.33), and 2.87 (2.86–2.88) mmol/L, respectively. Overall, the age-standardized prevalence of dyslipidemia was 32.21% (42.85% in men vs. 26.16% in women) in Chinese rural adults, with 5.11, 16.00, 19.27, and 4.76% for high TC, high TG, low HDL-C and high LDL-C, respectively. The age-standardized awareness, treatment and control of dyslipidemia were 15.07, 7.23, and 3.25%, respectively, which were higher in women than men, and increased steeply with age (Ptrend < 0.05). The proportion of prevalence, awareness, treatment, control of dyslipidemia differed significantly among various subpopulations while the awareness, treatment, and control rates were universally low in all subgroups (< 54, 36, and 15%, respectively). Increasing age, men, unhealthy lifestyles, positive family history of dyslipidemia, abnormal weight, type 2 diabetes mellitus and hypertension were independent risk factors of dyslipidemia. Conclusion: Dyslipidemia was common with unacceptably low awareness, treatment and control rates in rural China. Therefore, effective strategies are necessary for improving the status of the prevention, diagnosis, treatment, control of dyslipidemia in Chinese rural residents. Trial registration: ChiCTR-OOC-15006699 [ABSTRACT FROM AUTHOR]