The hypervirulent ST65 and ST25K. pneumoniae, along with carbapenem-resistant clonal populations ST11, appear to have evolved into cr-hvKP strains. The evidence of bi-directional evolution and emergence of hospital-acquired multi-clone cr-hvKP indicates a confluence of virulence and carbapenem resistance, which might pose major problems in the management of K. pneumoniae infection.

Background: Children with vitamin A, D, and E deficiency are susceptible to respiratory infections.However, the correlations between the levels with Mycoplasma pneumoniae pneumonia (MPP) and patient MPP occurrence is still unclear. This study aims to measure and compare the serum levels in severe (sMPP) and non-severe MPP (nsMPP) and to investigate the correlations between their levels and the occurrence of MPP. Methods: A total of 122 children were enrolled, including 52 sMPP and 70 nsMPP aged 0-15 years old in 2015-2018. The serum levels of vitamins A, D, and E were measured and compared, and two-category logistic regression was used for correlation analysis of vitamins A, D, and E levels with nsMPP and sMPP. Results: The age was older (7.12 vs. 4.01 y, P=0.002) in the sMPP samples than that in the nsMPP samples. Vitamin A deficiency was present in both the nsMPP and sMPP samples; its level was significantly lower (0.15±0.06 vs. 0.19±0.07, P=0.0193) in the sMPP serum than that in the nsMPP serum. Vitamins E and D in the sMPP samples were significantly lower (vitamin E 7.43±1.55 vs. 8.22±2.22, P=0.0104; vitamin D 23.08±11.0 vs. 32.07±19.2, P=0.0007) than that in the nsMPP group; both sMPP and nsMPP did notshow a deficiency of vitamins E and D. Logistic regression analysis revealed that vitamin A deficiency was significantly (OR 0.001, 95% CI: 0.001-0.334, P=0.009) associated with sMPP, and vitamin A supplementation could reduce the incidence of sMPP. In ≥6 y sMPP, the incidence of vitamin A deficiency was 62.5%, while <6 y, 85%, showing a significant difference. Vitamin A level in <6 y sMPP was significantly lower than that in ≥6 y sMPP.Conclusions: Vitamin A deficiency is associated with sMPP and more likely present in the younger sMPP samples. Therefore, it is important to watch and supplement vitamin A in M. pneumoniae infection patients.

This study investigated the detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) neutralizing antibodies following inoculation with the coronavirus disease (COVID-19) vaccine. From June to July 2021, 127 participants who had completed COVID-19 vaccination (inactivated SARS-CoV-2 vaccine, 64; CoronaVac, 61; CanSino, 2) were recruited and tested using SARS-CoV-2 neutralizing antibody kits. The positive detection rate (inhibition of neutralizing antibodies ≥ 30%) was calculated and stratified according to population characteristics and inoculation time. The positive rate of neutralizing antibody was 47.22% (17/36) in men and 53.85% (49/91) in women, and 54.55% (24/44) in BMI ≥ 24 and 50.60% (42/83) in BMI < 24. Age was stratified as 20–29, 30–39, 40–49, and ≥50; positive detection rates of SARS-CoV-2 neutralizing antibodies were observed in 60.00% (24/40), 50.00% (21/42), 48.39% (15/31), and 42.86% (6/14), respectively, but with no significant difference (x2 = 1.724, p = 0.632). Among 127 vaccinated participants, 66 (51.97%) were positive. The positive detection rate was 63.93% (39/61) with CoronaVac and 42.19% (27/64) with the inactivated SARS-CoV-2 vaccine (significance x2 = 5.927, p = 0.015). Multivariate analysis revealed a significant difference in vaccination times, with average vaccination weeks in the positive and negative groups of 11.57 ± 6.48 and 17.87 ± 9.17, respectively (t= −4.501, p < 0.001). The positive neutralizing antibody rate was 100.00%, 60.00%, 58.33%, 55.56%, 43.14%, 28.57%, and 0.00% at 2–4, 5–8, 9–12, 13–16,17–20, 21–24, and >24 weeks, respectively (x2 = 18.030, p = 0.006). Neutralizing antibodies were detected after COVID-19 inoculation, with differences relating to inoculation timing. This study provides a reference for vaccine evaluation and follow-up immunization strengthening.

Background: The outbreak of the novel 2019 coronavirus disease was declared a global pandemic by the World Health Organization (WHO) on March 11, 2020. The diagnosis of COVID-19 is frequently based on a positive serological test. We noted the occurrence of false-positive results for COVID-19 in the colloidal gold-based immunochromatographic strip (ICS) assay in sera from patients with autoimmune diseases (ADs). This study aimed to evaluate the possible reasons for the false-positive results in two ICS assays (Wondfo ICS and Innovita ICS) and to investigate the effect of urea dissociation in reducing false-positive results.Methods: The sera of 135 patients with ADs, 13 confirmed COVID-19 patients, 95 disease controls, and 120 healthy controls were tested for immunoglobin M (IgM) and IgG against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) using Wondfo and Innovita ICS kits. The distributions of auto-antibodies in antibody-positive and antibody-negative groups were also compared, and bivariable logistic regression was used to assess auto-antibodies associated with false-positive results. A urea dissociation test of ICS was performed for the SARS-CoV-2 antibody-positive samples.Results: Specificity of Wondfo ICS for the 95 disease controls was 94.74% compared to 98.95% and 96.84% for Innovita SARS-CoV-2 IgM and IgG, respectively. Specificity of Wondfo ICS for the 120 healthy controls was 97.5% compared to 100% and 99.17% for Innovita SARS-CoV-2 IgM and IgG, respectively. Specificity of Wondfo ICS for AD patients was 73.33% compared to 97.78% and 96.30% for Innovita SARS-CoV-2 IgM and IgG, respectively. Sensitivity was 74.07% for Wondfo compared to 70.37% for Innovita IgM and 66.67% for Innovita IgG. Using the Wondfo ICS, the percentage of elevated rheumatoid factor (RF) level (>20 IU/mL) was higher in the SARS-CoV-2 antibody-positive group compared with the antibody-negative group [27/36 (75.0%) vs. 34/99 (34.34%), P=0.001]. The elevated RF was associated with antibody positivity, with an odds ratio of 4.671 [95% confidence interval (CI), 1.88-11.69]. The specificity of the Wondfo ICS assay for the AD patients was increased from 73.33% to 94.07% after the urea dissociation assay.Conclusions: An elevated serum RF level could lead to false-positive results when detecting SARS-CoV-2 antibodies using the Wondfo ICS kit, and the urea dissociation assay would be helpful in reducing the incidence of false-positive results.

statementVascular noninflammatory molecule 1 (Vannin-1) is elevated in the intrauterine growth retardation (IUGR) asthmatic mice, leading to activation of the PI3K/Akt/NFκB pathway responsible for bronchial oxidative stress and hyperresponsiveness. AbstractIntrauterine growth retardation (IUGR) has high risk of developing bronchial asthma in childhood, whereas the underlying mechanisms remain unclear. This study aimed to disclose the role of vascular noninflammatory molecule 1 (vannin-1, encoded by the Vnn1 gene) and its downstream signaling in the IUGR asthmatic mice induced by ovalbumin. More significant histological alterations and increase of vannin-1 expressions were revealed in IUGR asthmatic mice, accompanied by elevated methylation of Vnn1 promoter regions. In IUGR asthmatic mice, we also found i) a direct binding of HNF4α and PGC1α to Vnn1 promoter by CHIP assay; ii) a direct interaction of HNF4α with PGC1α; iii) upregulation of phospho-PI3K p85/p55 and phospho-Akt Ser473 and downregulation of phospho-PTENT yr366 ; iv) increase in nuclear NFκB p65 and decrease in cytosolic IκB-α. In primary cultured bronchial epithelial cells derived from the IUGR asthmatic mice, knockdown of Vnn1 prevented upregulation of phospho-Akt Ser473 and increase of reactive oxygen species (ROS) and TGF-β production. Taken together, we demonstrate that elevated vannin-1 activates the PI3K/Akt/NFκB signaling pathway, leading to ROS and inflammation reactions responsible for asthma occurrence in IUGR. We also disclose that interaction of PGC1α and HNF4α promotes methylation of Vnn1 promoter regions and then upregulates vannin-1 expression.Biology Open • Accepted manuscript by guest on August 5, 2020 http://bio.biologists.org/ Downloaded from

Background: The epidemiology and economic burden of hospitalized community-acquired pneumonia (CAP) children due to MP is still poorly understood. This study aimed to investigate the dynamic changes of Mycoplasma pneumoniae pneumonia (MPP) in children in a general hospital.Methods: A total of 2011 CAP children aged 1-16 years hospitalized at Peking University Third Hospital from 2017 to 2019 were enrolled by cross-sectional study for the retrospective analysis of the clinical data mainly including seasonal distribution of MPP, hospital stay, severity, complications, use of flexible bronchoscopy, and hospitalization costs. The dynamic changes of CAP and MPP children within 3 consecutive years and the differences between the MPP group and non-MPP groups were compared. Results:The proportion of CAP children among hospitalized children was 32.4%, 38.5%, and 39.5% in 2017, 2018, and 2019, respectively, showing an upward trend (P<0.05).The prevalence rate of MPP was highest in the third quarter (30.2%) and the fourth quarter (39.2%) and lowest in the second quarter (13.2%) (χ 2 =51.8, P<0.05). Compared with the non-MPP group, the MPP group had significantly higher incidence of severe pneumonia (19.4% vs. 12.0%, χ 2 =20.99), incidence of complications (16.1% vs. 6.5%, χ 2 =48.24), proportion of patients undergoing flexible bronchoscopy (38.4% vs. 9.0%, χ 2 =252.79), and hospitalization costs (all P<0.05), along with significantly longer hospital stay (6 vs. 4 days, z=−11.131). A dynamic comparison of the clinical characteristics of MPP in 3 years showed that the number of children with MPP increased significantly in preschoolers in 2018 (37.3%) and in school-aged or older children in 2019 (53%) (P<0.05). MPP peaks occurred in August 2018 and November 2019. The total hospitalization costs, examination fees, and non-medication treatment costs increased significantly (the z values were 35.24, 46.79, and 9.64, respectively; P<0.05) year by year among MPP children; there was no significant difference in the medication cost over these 3 years (z=4.81, P>0.05). Conclusions:The proportions of severe pneumonia, complications, and use of flexible bronchoscopy as well as the hospitalization days and costs are higher in MPP children. General hospitals should develop integrated clinical quality control programs for MPP children, so as to optimize the allocation of medical resources.

Aim: Antofloxacin hydrochloride is a new fluoroquinolone antibiotic with broad-spectrum in vitro activity. Using the neutropenic murine thigh infection model, we defined the pharmacodynamic profile and property of antofloxacin hydrochloride against Staphylococcus aureus. Methods: Single-dose pharmacokinetic studies of antofloxacin hydrochloride were carried out in thigh infected mice. Therapy was initiated at 2 h postinoculation with 5-640 mg/kg per d fractionated for different dosing regimens. The thighs were removed for bacterial measurement after 24 h of therapy, the best pharmacokinetic/ pharmacodynamic (PK/PD) index correlated with the efficacy was determined by nonlinear regression analysis. A sigmoid E max dose-response model was used to estimate the daily dose and AUC 24 h /MIC (minimal inhibitory concentration) required to achieve a static effect. Results: The PK was linear with similar elimination half-life over the dose range studied. The AUC 24 h /MIC ratio was the PK/PD parameter that best correlated with efficacy (R 2 =92.3%, 90.8% for the two organisms, compared with C max /MIC and T>MIC [%], respectively). The 24 h static dose ranged from 34.3 to 153.7 mg/kg per d for all S aureus strains, the total AUC 24 h /MIC ratio to achieve bacteriostatic effect varied from 31.7 to 122.5 (mean, 65.7±30.6). Conclusion: Antofloxacin hydrochloride showed powerful antibacterial activity against the S aureus isolates used in our neutropenic infected mice model. Our data suggested that the AUC/MIC ratio appeared to be most closely linked to the bacterial outcome (R 2 >90%), and a total AUC 24 h /MIC ratio of 65.7 appears to be the target value to achieve a net bactericidal activity against S aureus, similar to the results of other fluoroquinolones.

Introduction: Reports of hypermucoviscous Klebsiella pneumoniae (hvKP) isolated from fluids other than blood or abscess are rare. The aim of the study was to compare clinical and microbiological characteristics of hvKP found in blood or abscess fluid with those isolated from other loci. Methodology: A total of 24 non-repetitive hvKP isolates were collected from January 2013 to June 2014 from patients with hvKP infections. There were 15 in Group 1 (fluid other than blood or abscess) and 9 in Group 2 (blood or abscess fluid). Medical records of all patients were reviewed. Capsular polysaccharide (CPS) typing, virulence factor determination, and multilocus sequence typing (MLST) of hvKP isolates were performed. Results: Seventeen sequence types (STs) and 6 capsular serotypes were identified. Type K2 CC65 was most commonly identified in Group 1 and type K2 CC86 in Group 2. Deletion of pLVPK-derived loci were found in K2 and non-K1/K2 hvKP strains. Two virulent genes, fimH and ycfM, were identified more frequently in Group 2 than in Group 1. There was no difference in the frequency of other virulent genes or serotypes in the two groups. Two imipenem resistant hvKP isolates (cr-hvKP) were found in non-blood or abscess samples. Conclusions: hvKP isolated from different body fluids had similar clinical and microbiological characteristics. cr-hvKP identified in non-blood or abscess samples should raise our attention to the challenging situation and management of hvKP infection.