Detection of pathogens from venous or arterial blood of patients with left-sided infective endocarditis by metagenomic next-generation sequencing: A prospective study.

BACKGROUND: Infective endocarditis is a life-threatening uncommon infectious disease, and we aimed to explore the clinical utility of venous or arterial blood-based metagenomic next-generation sequencing (mNGS) approaches to diagnose left-sided infective endocarditis (LSIE). METHODS: We prospectively studied 79 LSIE patients who received valvular surgery in our hospital. Results of blood culture, valve culture, venous blood-based mNGS, arterial blood-based mNGS, venous blood-based mNGS plus blood culture, and arterial blood-based mNGS plus blood culture were evaluated and compared. RESULTS: Both venous blood- and arterial blood-based mNGS methods displayed significantly higher positive detection rates than blood culture and valve culture (43.0 %, 49.4 % vs. 32.9 %, 19.0 %; P < 0.001). Strikingly, when combining blood-based mNGS and blood culture, the positive rate could be further improved to more than 60 %. Moreover, we found mNGS LSIE detection was closely associated with preoperative leukocyte (P = 0.027), neutrophil value (P = 0.018), vegetation ≥ 14 mm (P = 0.043), and vegetations in aortic valve (P = 0.048). In addition, we discovered that blood-based mNGS had a superir capacity over blood culture to detect gram-negative bacteria, fungi, Bartonella Quintana, and mixed infections than blood culture. CONCLUSION: This study indicates that venous blood- and arterial blood-based mNGS displayed high positive rate in the rapid detection of pathogens in high-risk LSIE patients.

Omicron variants breakthrough infection elicited higher specific memory immunity than third dose booster in healthy vaccinees.

Homologous booster, heterologous booster, and Omicron variants breakthrough infection (OBI) could improve the humoral immunity against Omicron variants. Questions concerning about memory B cells (MBCs) and T cells immunity against Omicron variants, features of long-term immunity, after booster and OBI, needs to be explored. Here, comparative analysis demonstrate antibody and T cell immunity against ancestral strain, Delta and Omicron variants in Omicron breakthrough infected patients (OBIPs) are comparable to that in Ad5-nCoV boosted healthy volunteers (HVs), higher than that in inactivated vaccine (InV) boosted HVs. However, memory B cells (MBCs) immunity against Omicron variants was highest in OBIPs, followed by Ad5-nCoV boosted and InV boosted HVs. OBIPs and Ad5-nCoV boosted HVs have higher classical MBCs and activated MBCs, and lower naïve MBCs and atypical MBCs relative to both vaccine boosted HVs. Collectively, these data indicate Omicron breakthrough infection elicit higher MBCs and T cells against SARS-CoV-2 especially Omicron variants relative to homologous InV booster and heterologous Ad5-nCoV booster.

Ad5-nCoV booster and Omicron variant breakthrough infection following two doses of inactivated vaccine elicit comparable antibody levels against Omicron variants.

Little information is available for antibody levels against SARS-CoV-2 variants of concern induced by Omicron breakthrough infection and a third booster with an inactivated vaccine (InV) or Ad5-nCoV in people with completion of two InV doses. Plasma was collected from InV pre-vaccinated Omicron-infected patients (OIPs), unvaccinated OIPs between 0 and 22 days, and healthy donors (HDs) 14 days or 6 months after the second doses of an InV and 14 days after a homogenous booster or heterologous booster of Ad5-nCoV. Anti-Wuhan-, Anti-Delta-, and Anti-Omicron-receptor binding domain (RBD)-IgG titers were detected using enzyme-linked immunosorbent assay. InV pre-vaccinated OIPs had higher anti-Wuhan-, anti-Delta-, and anti-Omicron-RBD-IgG titers compared to unvaccinated OIPs. Anti-Wuhan-RBD-IgG titers sharply increased in InV pre-vaccinated OIPs 0-5 days postinfection (DPI), while the geometric mean titers (GMTs) of anti-Delta- and anti-Omicron-RBD-IgG were 3.3-fold and 12.0-fold lower. Then, the GMT of anti-Delta- and anti-Omicron-RBD-IgG increased to 35 112 and 28 186 during 11-22 DPI, about 2.6-fold and 3.2-fold lower, respectively, than the anti-Wuhan-RBD-IgG titer. The anti-Wuhan-, anti-Delta-, and anti-Omicron-RBD-IgG titers declined over time in HDs after two doses of an InV, with 25.2-fold, 5.6-fold, and 4.5-fold declination, respectively, at 6 months relative to the titers at 14 days after the second vaccination. Anti-Wuhan-, anti-Delta-, and anti-Omicron-RBD-IgG titers elicited by a heterologous Ad5-nCoV booster were significantly higher than those elicited by an InV booster, comparable to those in InV pre-vaccinated OIPs. InV and Ad5-nCoV boosters could improve humoral immunity against Omicron variants. Of these, the Ad5-nCoV booster is a better alternative.

Association of plasma cystatin C with all-cause and cause-specific mortality among middle-aged and elderly individuals: a prospective community-based cohort study.

We investigated the associations of plasma cystatin C with all-cause and cause-specific mortality risk and identified potential modifying factors affecting these associations in middle-aged and elderly people (≥ 50 years). This community-based prospective cohort study included 13,913 individuals aged ≥ 50 years from the Health and Retirement Study. Cox proportional hazard models were used to estimate the associations between cystatin C concentrations and the risk of all-cause and cardiovascular and cancer mortality after adjustment for sociodemographic characteristics, lifestyle factors, self-reported medical history, and other potential confounding factors. During a total of 71,988 person-years of follow-up (median: 5.8 years; interquartile range 3.3-7.6 years), 1893 all-cause deaths were documented, including 714 cardiovascular-related and 406 cancer-related deaths. The comparisons of the groups with the highest (quartile 4) and lowest (quartile 1) cystatin C concentrations revealed that the adjusted hazard ratios and 95% confidence intervals were 1.92 (1.62-2.28) for all-cause mortality, 1.98 (1.48-2.65) for cardiovascular mortality, and 1.62 (1.13-2.32) for cancer mortality. The associations of cystatin C concentrations with all-cause, cardiovascular and cancer mortality did not differ substantially when participants were stratified by sex, age, BMI, current smoking status, current alcohol consumption, and regular exercise (all P for interactions > 0.05). Our study indicates that an elevated plasma cystatin C concentration is associated with an increased risk of all-cause, cardiovascular and cancer mortality both men and women among the middle-aged and elderly individuals.

A New Hemoglobin Variant: Hb Jiujiang [α18(A16)Gly→Cys, HBA2: c.55G>T].

We have identified a new α chain hemoglobin (Hb) variant in a Chinese subject. Sequencing of the α-globin gene revealed a mutation in exon 1 at nucleotide 55, which results in the replacement of a glycine by cysteine at codon 18 [α18(A16)Gly→Cys, HBA2: c.55G>T] that we have named Hb Jiujiang for the region of origin of the proband.

Downregulating miR-96-5p promotes proliferation, migration, and invasion, and inhibits apoptosis in human trophoblast cells via targeting DDAH1.

Several microRNAs (miRs) have been found to have modulating effects on trophoblast functions, yet the biological role and function of miR-96-5p and its interaction with Dimethylarginine Dimethylaminohydrolase 1 (DDAH1) remained poorly understood. After lentivirus transfection, the proliferation, migration, invasion and apoptosis of human trophoblast cells HTR-8/SVneo and SGHPL-4 were determined by Cell Counting Kit-8 (CCK-8) assay, scratch assay, Transwell, and flow cytometry, respectively. Relative expressions of miR-96-5p, DDAH1, and apoptosis-related proteins (B-cell lymphoma 2, Bcl-2; Bcl-2-associated X protein, Bax; cleaved (C) caspase-3) were detected via quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot as needed. The target gene of miR-96-5p and their potential binding sites were predicted using TargetScan V7.2 and confirmed by dual-luciferase reporter assay. MiR-96-5p downregulation promoted proliferation, migration and invasion, suppressed apoptosis, and decreased miR-96-5p expression in trophoblast cells in vitro, while miR-96-5p upregulation had the opposite effects. DDAH1 was recognized as a target gene of miR-96-5p, and silencing DDAH1 reversed the effects of miR-96-5p downregulation on the proliferation, migration, invasion and apoptosis of trophoblast cells as well as the expressions of apoptosis-related proteins. MiR-96-5p downregulation promotes proliferation, migration, and invasion, and suppresses apoptosis in human trophoblast cells in vitro via targeting DDAH1, which provides evidence for the implication of miR-96-5p in the functional modulation of trophoblasts.