Background: Novel coronavirus disease (COVID-19) is spreading globally. Little is known about the risk factors for the clinical outcomes of COVID-19 in children. Methods: A retrospective case-control study was taken in children with severe acute respiratory syndrome coronary virus-2 infection in Wuhan Children’s Hospital. Risk factors associated with the development of COVID-19 and progression were collected and analyzed. Results: Eight of 260 children diagnosed with severe COVID-19 pneumonia were included in the study. Thirty-five children with COVID-19 infection matched for age, sex and date of admission, and who classified as non-severe type, were randomly selected from the hospital admissions. For cases with severe pneumonia caused by COVID-19, the most common symptoms were dyspnea (87.5%), fever (62.5%) and cough (62.5%). In laboratory, white blood cells count was significantly higher in severe children than non-severe children. Levels of inflammation bio-makers such as hsCRP, IL-6, IL-10 and D-dimer elevated in severe children compared with non-severe children on admission. The level of total bilirubin and uric acid clearly elevated in severe children compared with non-severe children on admission. All of severe children displayed the lesions on chest CT, more lung segments were involved in severe children than in non-severe children, which was only risk factor associated with severe COVID-19 pneumonia in multivariable analysis. Conclusions: More than 3 lung segments involved were associated with greater risk of development of severe COVID-19 in children. Moreover, the possible risk of the elevation of IL-6, high total bilirubin and D-dimer with univariable analysis could identify patients to be severe earlier.

Background: Gastric cancer (GC) is a common malignant cancer with a poor prognosis. Ferroptosis has been shown to play crucial roles in GC development. Long non-coding RNAs (lncRNAs) is also associated with tumor progression in GC. This study aimed to screen the prognostic ferroptosis-related lncRNAs and to construct a prognostic risk model for GC. Methods: Ferroptosis-related lncRNAs from The Cancer Genome Atlas (TCGA) GC expression data was downloaded. First, single factor Cox proportional hazard regression analysis was used to select seven prognostic ferroptosis-related lncRNAs from TCGA database. And then, the selected lncRNAs were further included in the multivariate Cox proportional hazard regression analysis to establish the prognostic model. A nomogram was constructed to predict individual survival probability. Finally, we performed quantitative reverse transcription polymerase chain reaction (qRT-PCR) to verify the risk model. Results: We constructed a prognostic ferroptosis-related lncRNA signature in this study. Kaplan-Meier curve analysis revealed a significantly better prognosis for the low-risk group than for the high-risk group (P = 2.036e-05). Multivariate Cox proportional risk regression analysis demonstrated that risk score was an independent prognostic factor [hazard ratio (HR) = 1.798, 95% confidence interval (CI) =1.410–2.291, P < 0.001]. A nomogram, receiver operating characteristic curve, and principal component analysis were used to predict individual prognosis. Finally, the expression levels of AP003392.1, AC245041.2, AP001271.1, and BOLA3-AS1 in GC cell lines and normal cell lines were tested by qRT-PCR. Conclusions: This risk model was shown to be a novel method for predicting prognosis for GC patients.

CD19⁺CD24^hiCD38^hi transitional immature B-lymphocytes have been demonstrated to play an important role in regulating the alloimmune response in transplant recipients. Here, we analyzed the effect of calcineurin inhibition on these peripherally circulating regulatory B-cells (Breg) in renal transplant recipients receiving cyclosporine A (CsA) or tacrolimus. PBMCs from healthy subjects (HS) (n = 16) and renal transplant recipients (n = 46) were isolated. Flow cytometry was performed for CD19, CD24, CD38 and IL-10 either after isolation or after 72 hours of co-culture in presence of PMA/Ionomycin and TLR9-ligand in presence or absence of increasing concentrations of tacrolimus or CsA. The amount of CD19⁺ B-cells among lymphocytes was ∼9.1% in HS, ∼3.6% in CsA (n = 11, p<0.05) and ∼6.4% in TAC (n = 35, p<0.05) treated patients. Among B-cells, a distinct subset of Breg was found to be 4.7% in HS, 1.4% in tacrolimus treated patients and almost blunted in patients receiving CsA. Similarily, ∼4% of B-cells in HS and even fewer in CsA or tacrolimus treated patients produced IL-10 (0.5% and 1.5%, p<0.05) and this was confirmed both in non-transplanted CsA-treated healthy subjects and in in vitro co-culture experiments. Among 29 patients with 1%. Calcineurin inhibitors reduce number and IL-10 production of Bregs in the peripheral circulation of both renal transplant recipients and non-transplanted healthy subjects. CNI induced Breg reduction is not restricted to a solid organ transplant setting and is not mediated by co-medication with steroids or MPA. A low proportion of Breg cells is associated with an elevated frequency of allograft rejection events.

Recently, B cells with regulatory functions suppressing T-cell immunity were identified. Inflammation in the context of sepsis is characterized by a profound immune dysfunction increasing the patient’s risk for additional infections. The impact of endotoxemia on B-cell dynamics, regulatory B cells (Breg) and its contribution to immune dysfunction is unknown. It is the aim of the present study to characterize the dynamics of the B-cell compartment and Breg in an experimental human endotoxemia model. In this randomized placebo-controlled cross-over study, 20 healthy males received an intravenous injection of endotoxin (Escherichia coli lipopolysaccharide, LPS, 0.8 ng/kg body weight) or placebo (saline 0.9%) on two otherwise identical study days. B cells were analyzed by flow cytometry at baseline and repeatedly up to 72 h after endotoxin/placebo injection. Absolute CD19⁺ B cells counts showed a significant decrease 3 h after endotoxin injection. Memory B cells were partially depleted from the circulation; the total number of Breg was significantly diminished 3 h after LPS challenge. Production of anti-inflammatory interleukin (IL)-10 (IL-10) by Breg was unaltered after LPS challenge. Systemic B-cell activating factor (BAFF) levels were significantly increased with a maximum after 24 h and remained increased up to 72 h post-injection. Endotoxemia causes a transient depletion of memory B cells and Breg from the circulation. However, the functional capacity of B cells to produce IL-10 is not impaired.