Vaginal microecological imbalance and expression of serum inflammatory factors in pregnant women with group B streptococcus infection and pregnancy outcome.

The objective of this study was to explore the correlation between vaginal microecological imbalance and the expression of related inflammatory factors in pregnant women with group B streptococcus (GBS) infection and pregnancy outcomes. For this purpose, 100 GBS-positive pregnant women were recruited as the experimental group, and 100 GBS-negative pregnant women were recruited as the controls. The balance of vaginal microecology of pregnant women in different groups was compared. Results showed that the probability of vaginal microecological imbalance in the experimental group was much higher than against the controls. Fasting venous blood was drawn from the pregnant women in two groups. After centrifugation, the expression levels of interleukin-6 (IL-6), tumor necrosis factor α (TNF-α), and interleukin-1ß (IL-1ß) in serum were detected. It was found that the expression levels of IL-6, IL-1ß, and TNF-α in the experimental group were higher than against the controls. After delivery, it suggested that the incidence of premature delivery, neonatal infection, premature rupture of membranes, and other adverse childbirth in the experimental group was much higher in contrast to the controls, up to 87%. In conclusion, GBS infection can increase the incidence of vaginal microecological imbalance and the expression of serum inflammatory factors in pregnant women, and it can greatly raise the incidence of adverse pregnancy outcomes.

Clinical and laboratory features in health care volunteers with inactivated SARS-CoV-2 vaccination.

Background/aim: To better optimize the inactivated vaccine-induced immune response and improve vaccine protection efficiency, a preliminary study was conducted on the influencing factors of producing neutralizing antibody (NAb) titers against the inactivated coronavirus disease 2019 (COVID-19) vaccine. Materials and methods: A total of 91 health care volunteers were enrolled from the Immunology Division of the Laboratory Department of Chongqing General Hospital from February to March 2021. The study had a cross-sectional design. All of the volunteers were scheduled to receive a complete dose regimen of the inactivated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine and the vaccination interval between 2 doses was 14 days. Clinical and laboratory features were collected for further analysis. Results: The NAb titers gradually increased after COVID-19 vaccination, and 72.53% (n = 66) of the volunteers had NAbs after the second dose. Eight variables, including CD16+CD56+ NK cell level before the first dose (HR = 0.94, p = 0.02), CD16+CD56+ NK cell level after the second dose (HR = 0.94, p = 0.03), interleukin (IL)-2 level before the first dose (HR = 2.09, p = 0.05), mean corpuscular volume (HR = 0.86, p = 0.02), serum urea level (HR = 0.69, p = 0.05), increment of CD19+ B cells (HR = 0.86, p = 0.03), increment of CD4+/CD8+ T cells (HR = 0.21, p = 0.03), and increment of the IL-6 level (HR = 0.75, p = 0.04) demonstrated a correlation with the NAb titers after COVID-19 vaccination. In the multivariate logistical regression analysis, the serum urea level (HR = 2.32, P = 0.03) and increment of CD19+ B cells (HR = 1.96, p = 0.03) were positively correlated with the NAb titers. The principal component analysis effectively distinguished the response after COVID-19 vaccination. The Pearson correlation analysis indicated that the CD19+ B cell level (r = 0.23, p < 0.001) and IL-2 (r = 0.24, p < 0.001) and IL-6 levels (r = 0.22, p < 0.001) were weakly positively correlated with the concentration of NAbs. Conclusion: The NAbs titers of the inactivated vaccines were positively correlated with the ratio of CD19+ B cell, IL-6, and IL-2 levels in the serum, which provide clinical guidance for inactivated SARS-CoV-2 vaccines.

WeChat-based vestibular rehabilitation for patients with chronic vestibular syndrome: protocol for a randomised controlled trial.

INTRODUCTION: Dizziness is one of the most common symptoms seen in chronic vestibular syndrome, which has been linked to an increased risk of falls, substantial disability and negative psychological consequences. Recent evidence demonstrated that vestibular rehabilitation therapy (VRT) is effective for treating chronic vestibular symptoms. However, the delivery of VRT remains challenging because of lack of facility, insufficient qualified physiotherapist resources, as well as being in the actual situation of the pandemic. WeChat, the most widely used mobile app in China, offers a more viable way of delivering VRT than traditional office-based approaches do. This study aimed to evaluate the effectiveness of the WeChat-VRT programme for patients with chronic vestibular syndrome. METHODS AND ANALYSIS: This is a parallel-group, assessor-blinded randomised controlled trial. Fifty patients who experienced chronic vestibular symptoms longer than 3 months will be randomised into either the WeChat-VRT group or the usual care (UC) group. Participants in the WeChat-VRT group will receive 8-week VRT mainly through the WeChat app. Participants in the UC group will receive once-weekly VRT in the clinic for 8 weeks and remaining time home-based exercise. Outcome assessments will take place at baseline and at the 8th, 12th and 24th weeks after randomisation. The primary outcome will be the change from baseline to the eighth week on the patients' functional improvements quantified by the Functional Gait Assessment (FGA). The secondary outcomes will include dynamic balance function, emotional well-being, and vestibular activity and participation level. Intention-to-treat analysis will be performed using generalised estimation equation modelling. ETHICS AND DISSEMINATION: The trial has been reviewed and approved by the Institutional Review Board of Eye and Ear Nose Throat Hospital of Fudan University (reference number 2017047/1). The study findings will be disseminated via peer-reviewed journals and conferences. TRIAL REGISTRATION NUMBER: ChiCTR2000029457; Pre-results.

Mutations in inherited fibrinogen disorders correlated with clinical features in the Chinese population.

Two probands with unknown reasons for low fibrinogen activity were considered to investigate the association between mutations in inherited fibrinogen disorders (IFDs) and clinical features in the Chinese population. A routine coagulation test was conducted on a Sysmex CS5100 coagulation analyzer, and Sanger sequencing was employed to analyze mutations. A PubMed database search through May 2020 was performed to identify relevant studies regarding the congenital fibrinogen disorder epidemic in China. A common heterozygous missense mutation (c.1233G > A p.Arg35His), a novel heterozygous mutation (c.2014T > C p.Trp672Arg), and a novel homozygous mutation (c.16A > G p.Ile6Val) in the FGA gene were identified in two probands with dysfibrinogenemia. The global coagulation screening assay can distinguish four types of IFD, especially a ratio of Fib:Ag/Fib:C equal to 1.5, which can distinguish patients with hypofibrinogenemia from those with hypodysfibrinogenemia. A total of 81 mutations from 76 probands in 45 IFD families have been reported in the Chinese population. Arg35 in FGA and Arg301 in FGG were responsible for IFD in more than half of patients in the Chinese population. It is possible to distinguish four types of IFD by using a global coagulation screening assay. Mutations in FGA, FGB and FGG occur in different functional regions, and Arg changes account for more than 70% of patients with IFD in the Chinese population, especially Arg-Cys, which may be associated with severe clinical symptoms.

Identification of a prognostic signature based on copy number variations (CNVs) and CNV-modulated gene expression in acute myeloid leukemia.

OBJECTIVES: Acute myeloid leukemia (AML) is caused by multiple genetic alterations in hematopoietic progenitors, and molecular genetic analyses have provided useful information for AML diagnosis and prognostication. This study aimed to integratively understand the prognostic value of specific copy number variation (CNV) patterns and CNV-modulated gene expression in AML. METHODS: We conducted integrative CNV profiling and gene expression analysis using data from the Therapeutically Applicable Research To Generate Effective Treatments (TARGET) and The Cancer Genome Atlas (TCGA) AML cohorts. CNV-related genes associated with survival were identified using the TARGET AML cohort and validated using the TCGA AML cohort. Genes whose CNV-modulated expression was associated with survival were also identified using the TARGET AML cohort and validated using the TCGA AML cohort, and patient bone marrow samples were then used to further validate the effects of CNV-modulated gene expression on survival. CNV and mRNA survival analyses were conducted using proportional hazards regression models (Cox regression) and the "survminer" and "survival" packages of the R Project for Statistical Computing. Genes belonging to the Kyoto Encyclopedia of Genes and Genomes (KEGG) cancer panel were extracted from KEGG cancer-related pathways. RESULTS: One hundred two CNV-related genes (located at 7q31-34, 16q24) associated with patient survival were identified using the TARGET cohort and validated with the TCGA AML cohort. Among these 102 validated genes, three miRNA genes (MIR29A, MIR183, and MIR335) were included in the KEGG cancer panel. Five genes (SEMA4D, CBFB, CHAF1B, SAE1, and DNMT1) whose expression was modulated by CNVs and significantly associated with clinical outcomes were identified, and the deletion of SEMA4D and CBFB was found to potentially exert protective effects against AML. The results of these five genes were also validated using patient marrow samples. Additionally, the distribution of CNVs affecting these five CNV-modulated genes was independent of the risk group (favorable-, intermediate-, and adverse-risk groups). CONCLUSIONS: Overall, this study identified 102 CNV-related genes associated with patient survival and identified five genes whose expression was modulated by CNVs and associated with patient survival. Our findings are crucial for the development of new modes of prognosis evaluation and targeted therapy for AML.

Performance verification of anti-SARS-CoV-2-specific antibody detection by using four chemiluminescence immunoassay systems.

OBJECTIVES: The purpose of the current study was to evaluate the analytical performance of seven kits for detecting IgM/IgG antibodies against coronavirus (SARS-CoV-2) by using four chemiluminescence immunoassay systems. METHODS: Fifty patients diagnosed with SARS-CoV-2 infection and 130 controls without coronavirus infection from the General Hospital of Chongqing were enrolled in the current retrospective study. Four chemiluminescence immunoassay systems, including seven IgM/IgG antibody detection kits for SARS-CoV-2 (A_IgM, A_IgG, B_IgM, B_IgG, C_IgM, C_IgG and D_Ab), were employed to detect antibody concentrations. The chi-square test, the receiver operating characteristic (ROC) curve and Youden's index were determined to verify the cut-off value of each detection system. RESULTS: The repeatability verification results of the A, B, C and D systems are all qualified. D_Ab performed best (92% sensitivity and 99.23% specificity), and B_IgM performed worse than the other systems. Except for the A_IgM and C_IgG systems, the optimal diagnostic thresholds and cut-off values of the other kits and their recommendations are inconsistent with each other. B_IgM had the worst AUC, and C_IgG had the best diagnostic accuracy. More importantly, the B_IgG system had the highest false-positive rate for testing patients with AIDS, tumours and pregnancies. The A_IgM system test showed the highest false-positive rates among elderly individuals over 90 years old. COVID-2019 IgM/IgG antibody test systems exhibit performance differences. CONCLUSIONS: The Innodx Biotech Total Antibody serum diagnosis kit is the most reliable detection system for anti-SARS-CoV-2 antibodies, which can be used together with nucleic acid tests as an alternative method for SARS-CoV-2 detecting.

A Novel Electrochemiluminescent Immunoassay Based on Target Transformation Assisted with Catalyzed Hairpin Assembly Amplification for the Ultrasensitive Bioassay.

In this work, we constructed a novel electrochemiluminescent (ECL) strategy based on sandwich immunoassay-induced target transformation assisted with catalyzed hairpin assembly (CHA) amplification for ultrasensitive bioassay with cysteine-rich protein 61 (CCN1) as a model. First, the target CCN1 could be equally transformed into the specific oligonucleotide (initiator I) labeled on the detection antibody based on the specific sandwich immunoassay. In addition, the initiator I triggered an efficient nonenzymatic CHA amplification in the presence of ferrocene-labeled hairpin 1 (Fc-H1) and hairpin 2 (H2) to produce massive hybrids (Fc-H1-H2) containing a sticky end labeled with ferrocene. Finally, Fc-H1-H2 could be immobilized on the capture probe single-stranded DNA (ssDNA)-modified electrode through the hybridization between the sticky end of Fc-H1-H2 and ssDNA, and a significantly quenched ECL signal could be obtained due to the efficient quench effect between ferrocene and the ECL indicator, ruthenium(II) tris(4,4'-dicarboxylicacid-2,2'-bipyridyl) [Ru(dcbpy)32+], immobilized on the surface of the electrode, which was related to the concentration of target CCN1. As expected, the proposed ECL biosensor exhibited a relatively low detection limit of 3.9 fg/mL in a linear range from 10 fg/mL to 100 ng/mL. This ECL strategy inspired the clinical examination of the biomarker CCN1, providing potential application in early diagnosis and malignant monitoring of cancer.

Polymorphisms of the CYR61 gene in patients with acute myeloid leukemia in a Han Chinese population.

It was demonstrated in previous studies that cysteine-rich angiogenic inducer 61 (Cyr61) plays vital roles in hematological disorders, and we have already reported that the Cyr61 protein is a tumor promoter in acute myeloid leukemia (AML). Here, we investigated the association between CYR61 gene polymorphisms and susceptibility to AML.We genotyped 2 single-nucleotide polymorphisms (rs2297141 and rs6576776) in the region of the CYR61 gene by improved multiplex ligase detection reaction genotyping assays in a total of 275 samples, including samples from 137 AML patients and 138 healthy controls. Chi-squared tests and logistic regression analysis were performed to compare the different distributions of the genotypes and alleles between patients and healthy controls.The rs2297141 A allele was associated with lower risk of AML compared with the G allele (odds ratio [OR] = 0.704, 95% confidence interval [CI] = 0.503-0.985, P = .04) in both the dominant (OR = 0.447, 95% CI = 0.22-0.909, P = .025, AA vs GG) and recessive inheritance models (OR = 0.419, 95% CI = 0.23-0.763, P = .004, AA vs GA + GG). Although the distribution of the rs6576776 alleles was not different between patients with AML and normal controls, the CC genotype significantly increased the risk of AML in the dominant inheritance model (OR = 6.064, 95% CI = 1.303-28.216, P = .01, CC vs GG) and the recessive inheritance model (OR = 5.937, 95% CI = 1.291-27.306, P = .01, CC vs GC + GG). Additionally, it was shown that the rs2297141 and rs6576776 genotypes were associated with AML-M5 and AML-M2, respectively.Our findings indicated that genetic polymorphisms in the CYR61 gene may be considered potential AML risk factors in the Han Chinese population.

Ultrasensitive electrochemiluminescence biosensor for detection of laminin based on DNA dendrimer-carried luminophore and DNA nanomachine-mediated target recycling amplification.

Herein, a novel electrochemiluminescence (ECL) biosensor was proposed for ultrasensitive detection of laminin (LN), in which DNA dendrimer (D) as a promising nanocarrier for luminophore and DNA nanomachine as tactic for target recycling. The DNA dendrimer was synthesized by hybridization between sense and its antisense Y-shaped DNAs which were formed via reaction between single-stranded DNA (ssDNA) with a thiol group at the 5'-end and a synthesized trimeric cross-linker of tris(2-maleimidoethyl)amine. This dendrimer provided abundant double-stranded DNA (dsDNA) to achieve high loading efficiency for ECL luminophore. Simultaneously, N-(aminobutyl)-N-(ethylisoluminol) (ABEI) was conjugated with doxorubicin (Dox, a intercalator of dsDNA) to form the ECL indicator (Dox-ABEI) which could effectively intercalate DNA dendrimer to form the ECL probe (D-Dox-ABEI). Subsequently, a DNA nanomachine activated by target protein was involved to obtain numerous output ssDNA (S2) which was amplified by exonuclease III-assisted recycle and immobilized on ssDNA (S1)-modified sensing electrode surface via complementation. Thereby, abundant D-Dox-ABEI probes were captured by S2 to construct the biosensor for target protein detection. The proposed ECL biosensor realized the ultrasensitive detection of LN with a linear range from 0.1pg/mL to 100ng/mL and a low detection limit of 0.0661pg/mL. Impressively, the application of this ECL biosensor would provide the great potential for analysis of other proteins, revealing a new avenue for early diagnosis and the prognosis evaluation of various diseases.

Signal molecule-dependent quorum-sensing and quorum-quenching enzymes in bacteria.

The quick spread of nosocomial bacterial infections and the increasing prevalence of drugresistant strains make the development of novel drugs for pathogens an urgent priority. Quorum sensing (QS) is a communication mechanism used by bacteria to recognize population density fluctuations and control gene expression, which play a critical role both in intraspecies and interspecies communications and regulates microbe-host interactions. Low-molecular-weight signal compounds, such as acyl-homoserine lactone and autoinducing peptide, are used by QS to control the expression of different pathogenic factors. Thus QS--and QS signal molecules in particular--is an attractive target for developing novel antimicrobial methods. Quorum-quenching enzymes, which hydrolyze or modify signal molecules in QS circuit systems to inhibit the expression of bacteria virulence factors, have been identified both in prokaryotes and eukaryotes. Understanding the mechanism of action of quorum-quenching enzymes also provides a promising means to control bacterial infection. This review first introduces the novel principle underling signal-based QS systems in several important pathogens and then focuses on the newly identified quorum-quenching enzymes, including lactonases, acylases, oxidoreductases, and paraoxonases; this summary introduces new concepts of antimicrobial infection.