Clinical efficacy of methylprednisolone and the combined use of lopinavir/ritonavir with arbidol in treatment of coronavirus disease 2019.

This study aims to comparatively analyze the therapeutic efficacy upon multiple medication plans over lopinavir/ritonavir (LPV/r), arbidol (ARB), and methylprednisolone on patients with coronavirus disease 2019 (COVID-19). Totally, 75 COVID-19 patients admitted to The First Affiliated Hospital, Zhejiang University School of Medicine from January 22, 2020 to February 29, 2020 were recruited and grouped based on whether or not LPV/r and ARB were jointly used and whether or not methylprednisolone was used. Indexes including body temperature, time for nucleic acid negative conversion, hospital stays, and laboratory indexes were examined and compared. For all patients, there were no significant differences in the change of body temperature, the time for negative conversion, and hospital stays whether LPV/r and ARB were jointly used or not. While for severe and critically severe patients, methylprednisolone noticeably reduced the time for negative conversion. Meanwhile, the clinical efficacy was superior on patients receiving methylprednisolone within 3 days upon admission, and the duration of hospital stays was much shorter when methylprednisolone was given at a total dose of 0-400 mg than a higher dose of >400 mg if all patients received a similar dose per day. Nonetheless, no significant changes across hepatic, renal, and myocardial function indexes were observed. LPV/r combined with ARB produced no noticeably better effect on COVID-19 patients relative to the single-agent treatment. Additionally, methylprednisolone was efficient in severe and critically severe cases, and superior efficacy could be realized upon its early, appropriate, and short-term application.

Interleukin-35 promotes Breg expansion and interleukin-10 production in CD19+ B cells in patients with ankylosing spondylitis.

OBJECTIVE: IL-35 is a potent immunosuppressive and anti-inflammatory cytokine, consisting of a p35 subunit and an Epstein-Barr virus-induced gene 3 (EBI3) subunit, which suppresses CD4+ effector T cell proliferation and promotes regulatory T cell (Treg) expansion. However, the effects of IL-35 on regulatory B cells (Bregs) in ankylosing spondylitis (AS) have not been explored. The present study aimed (i) to measure serum IL-35 levels and the percentages of Bregs in the peripheral blood of patients with AS and (ii) to explore their relationships in the pathogenesis of AS. METHODS: A total of 77 patients with AS (AS group), including 47 inactive AS and 30 active AS cases, and 59 healthy controls (HCs) were enrolled into this study. The serum levels of IL-35 and IL-10 were detected by ELISA, and the mRNA levels of p35 and EBI3 were measured by RT-qPCR. The percentages of CD19+CD24hiCD38hi and CD19+CD24hiCD27+ Bregs and IL-35 receptor (IL-12Rß2, IL-27Rα and gp130), IL-10, p-STAT1, p-STAT3, and p-STAT4 in CD19+ B cells were detected by flow cytometry. The correlations between IL-35 levels and percentages of Bregs were analyzed by determining Pearson's correlation coefficient. The effect of IL-35 on Bregs was determined by mix-culture of recombinant (r) IL-35 with peripheral blood mononuclear cells (PBMCs). RESULTS: The serum IL-35 and IL-10 levels, p35 and EBI3 mRNA levels, and the percentages of CD19+CD24hiCD38hi and CD19+CD24hiCD27+ Bregs were significantly lower in AS patients than those in HCs. In addition, the percentages of CD19+CD24hiCD38hi and CD19+CD24hiCD27+ Bregs in active AS patients were significantly lower than those in inactive AS patients. The serum IL-35 levels were positively correlated with the percentages of CD19+CD24hiCD38hi and CD19+CD24hiCD27+ Bregs in AS patients. IL-12Rß2 and IL-27Rα, but not gp130 subunit, were expressed in CD19+ B cells in AS patients. RIL-35 could effectively promote CD19+CD24hiCD38hi Breg expansion and IL-10 production. Meanwhile, rIL-35 also promoted the expression of IL-12Rß2 and IL-27Rα and the phosphorylation of STAT1 and STAT3 in CD19+ B cells. CONCLUSION: These results demonstrated that reduced IL-35 production may be associated with Bregs defects in AS patients. RIL-35 induced the proliferation of CD19+CD24hiCD38hi Bregs and IL-10 production, suggesting that IL-35 may serve as a reference for further investigation to develop novel treatments for AS. Key Points • Our study investigated the effects of IL-35 on Bregs in AS patients. • We found the serum IL-35, IL-10 levels, and the percentages of CD19+CD24hiCD38hi and CD19+CD24hiCD27+ Bregs were significantly lower in AS patients. • The serum IL-35 levels were positively correlated with the percentages of CD19+CD24hiCD38hi and CD19+CD24hiCD27+ Bregs in AS patients. • Recombinant IL-35 could effectively promote CD19+CD24hiCD38hi Breg expansion and IL-10 production.

Exploration of Prognostic Biomarkers for Lung Adenocarcinoma Through Bioinformatics Analysis.

With the development of computer technology, screening cancer biomarkers based on public databases has become a common research method. Here, an eight-gene prognostic model, which could be used to judge the prognosis of patients with lung adenocarcinoma (LUAD), was developed through bioinformatics methods. This study firstly used several gene datasets from GEO database to mine differentially expressed genes (DEGs) in LUAD tissue and healthy tissue via joint analysis. Later, enrichment analysis for the DEGs was performed, and it was found that the DEGs were mainly activated in pathways involved in extracellular matrix, cell adhesion, and leukocyte migration. Afterward, a TCGA cohort was used to perform univariate Cox, least absolute shrinkage and selection operator method, and multivariate Cox regression analyses for the DEGs, and a prognostic model consisting of eight genes (GPX3, TCN1, ASPM, PCP4, CAV2, S100P, COL1A1, and SPOK2) was established. Receiver operation characteristic (ROC) curve was then used to substantiate the diagnostic efficacy of the prognostic model. The survival significance of signature genes was verified through the GEPIA database, and the results exhibited that the risk coefficients of the eight genes were basically congruous with the effects of these genes on the prognosis in the GEPIA database, which suggested that the results were accurate. Finally, combined with clinical characteristics of patients, the diagnostic independence of the prognostic model was further validated through univariate and multivariate regression, and the results indicated that the model had independent prognostic value. The overall finding of the study manifested that the eight-gene prognostic model is closely related to the prognosis of LUAD patients, and can be used as an independent prognostic indicator. Additionally, the prognostic model in this study can help doctors make a better diagnosis in treatment and ultimately benefit LUAD patients.

Survival Outcome after Stereotactic Body Radiation Therapy and Surgery for Early Stage Non-Small Cell Lung Cancer: A Meta-Analysis.

OBJECTIVE: Treatment modalities in medically compromised patients with early-stage non-small cell lung cancer (NSCLC) are controversial. Stereotactic body radiotherapy (SBRT) or stereotactic ablative radiotherapy has been increasingly recognized as a favorable alternative to surgical resection for early-stage NSCLC. Many retrospective analyses compared the efficacy of stereotactic body radiotherapy (SBRT) with surgery for early-stage non-small cell lung cancer (NSCLC). However, the efficacy between SBRT and surgery regimens for patients with early-stage NSCLC remains unclear. This study aimed to investigate the efficacy between SBRT and surgery. METHODS: Publications on comparison SBRT with Surgery in treatment of early stage non-small cell lung cancer (NSCLC) from 2011 to 2017 were collected. Retrospective trials analyzed the summary hazard ratios (HRs) of overall survival (OS), disease-free survival (DFS), local control survival (LC), regional control survival (RC), loco-regional control survival (LRC), and distant control survival (DC) between SBRT and Surgery. The major outcomes measures were hazard ratios (HRs). Meta-analysis Revman 5.3 software was used to analyze the combined Pooled HRs using fixed- or random-effects models according to the heterogeneity. RESULT: A systematic literature search was conducted including14 studies. In this meta-analysis, patients with SBRT achieved inferior OS, DFS, LC, RC, LRC and DC, compared with surgery. CONCLUSION: In this study we found more favorable outcomes with stage I NSCLC treated with SBRT. The surgery had no obvious advantages in this meta-analysis. Although surgery has become the recommended treatment at present, SBRT has potential to be an alternative treatment as a novel non-invasive radiation therapy modality in patients with stage I-II NSCLC.

Role of p14ARF and p15INK4B promoter methylation in patients with lung cancer: a systematic meta-analysis.

BACKGROUND: The cyclin-dependent kinase inhibitors p14ARF and p15INK4B are tumor suppressor genes that have been reported to be silenced through promoter methylation in many human cancers. However, the strength of association between p14ARF or p15INK4B promoter methylation and lung cancer remains unclear. Thus, we first determined whether p14ARF and p15INK4B promoter methylation played a key role in the carcinogenesis of lung cancer. METHODS: Eligible studies were selected from the online electronic databases. The pooled odds ratios or hazard ratios and 95% confidence intervals were calculated and summarized. RESULTS: Finally, 12 studies with 625 lung cancer samples and 488 nontumor samples were included under the fixed-effects model. The pooled odds ratio showed that p14ARF promoter methylation was observed to be significantly higher in non-small-cell lung cancer (NSCLC) than in nontumor samples (P<0.001). No significant correlation was found between p15INK4B promoter methylation and lung cancer (P=0.27). Subgroup analysis of ethnicity revealed that p14ARF promoter methylation was significantly related to the risk of NSCLC in Asian and Caucasian populations. Subgroup analysis of sample type demonstrated that p14ARF promoter methylation was correlated with the risk of NSCLC in tissue samples (P<0.001), but not in bronchoalveolar lavage fluid and blood samples. P14ARF promoter methylation from one study was not significantly correlated with overall survival of patients with NSCLC. Promoter methylation of p14ARF and p15INK4B was not correlated with clinicopathological characteristics, such as gender status, smoking status, tumor differentiation, and tumor stage (P>0.05). CONCLUSION: Our findings suggested that p14ARF promoter methylation may play an important role in the carcinogenesis of lung cancer, but not p15INK4B promoter methylation. Promoter methylation of p14ARF and p15INK4B was not associated with clinicopathological parameters. However, more extensive large-scale studies are essential to further validate our study.