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Administration of Paxlovid in early stage has been proved to reduce the risk of hospitalization or death by 89% in mild to moderate COVID-19 patients with high-risk. There were few evidences of Paxlovid in severe COVID-19 patients. RECOVERY study has previously shown that the use of glucocorticoids reduces the risk of death in hospitalized COVID-19 patients requiring oxygen or ventilatory support. The efficacy of Paxlovid plus glucocorticoids in COVID-19 patients with hypoxaemia is unclear. In this multiple-centers prospective study, we collected the data of hospitalized adult Omicron infected subjects with hypoxaemia at 4 hospitals, who were treated with glucocorticoids or Paxlovid plus glucocorticoid. We compared the efficacy of Paxlovid plus glucocorticoids (P + GCS group) vs. glucocorticoids (GCS group). A 28-day composite outcome of disease progression was evaluated. Totally 266 Omicron infected patients with hypoxaemia were enrolled in this study. There was no difference in most of the baseline characteristics in two groups, including ages, sex and underlying diseases. The 28-day composite outcome in severe patients of P + GCS group was significantly lower than that of GCS group (16.9% vs. 33.8%, P = 0.013). The viral shedding time was shorter in P + GCS group than that in G group (6 days vs. 8 days, P = 0.015). The hospitalized time in severe patients of P + GCS group was significantly shorter than that of GCS group (15 days vs. 17 days, P = 0.0008). Cox analysis showed the benefit of P + GCS in sub-group of MODS, CRP ≥ 36 mg/L, d-dimer ≥1 µg/L, creatinine ≥ 90µmol/L). Our study demonstrated the benefit of Paxlovid plus glucocorticoid administration in hospitalized Omicron infection patients with hypoxaemia. These results, as least partly, supported direct evidence about the necessity of antiviral treatment in severe COVID-19 patients with hypoxaemia.

Non-small cell lung cancer (NSCLC) is the most commonly diagnosed lung cancer and is associated with poor prognosis. This study aimed to analyze if serum C-reactive protein (CRP), albumin (Alb), and CRP/Alb ratio could provide prognostic information in patients with NSCLC. 387 patients with primary NSCLC were included in this analysis. Cox proportional hazards regression was used to estimate hazard ratio (HR) and 95% confidence interval (CI) of death with adjustment for some potential confounders. The multivariate regression analyses revealed the statistically significant associations of decreased survival of patients with NSCLC with elevated CRP, decreased Alb, and elevated CRP/Alb ratio. The HRs of mortality were 1.56 (95% CI: 0.80–3.04) and 2.64 (95% CI: 1.35–5.16) for patients in the second and the highest tertiles of CRP ( P -trend = 0.003). For albumin, the HR was 0.50 (95% CI: 0.29–0.85) for the normal group. The CRP/Alb ratio strongly predicted the survival of patients in the highest tertile with a fourfold risk of dying compared with those in the lowest tertile (HR = 4.14, 95% CI: 2.15–7.98). The subgroup analysis according to various patient characteristics confirmed these associations. In conclusion, serum CRP, albumin, and CRP/Alb ratio are predictive of survival for Chinese patients with NSCLC.

Da-Xiong Zeng Department of Pulmonary and Critical Care Medicine, Dushu Lake Hospital Affiliated to Soochow University, Medical Center of Soochow University, Suzhou, People's Republic of ChinaCorrespondence: Da-Xiong Zeng, Department of Pulmonary and Critical Care Medicine, Suzhou Dushu Lake Hospital, No. 9, Chongwen Road, Suzhou, 215100, People's Republic of China, Email zengdaxiong@suda.edu.cn

Background Hypoxic pulmonary hypertension (HPH) is a common complication of chronic lung disease, which severely affects the survival and prognosis of patients. Several recent reports have shown that DNA damage and repair plays a crucial role in pathogenesis of pulmonary arterial hypertension. DNA-dependent protein kinase catalytic subunit (DNA-PKcs) as a part of DNA-PK is a molecular sensor for DNA damage that enhances DSB repair. This study aimed to demonstrate the expression and potential mechanism of DNA-PKcs on the pathogenesis of HPH. Methods Levels of DNA-PKcs and other proteins in explants of human and rats pulmonary artery from lung tissues and pulmonary artery smooth muscle cells (PASMC) were measured by immunohistochemistry and western blot analysis. The mRNA expression levels of DNA-PKcs and NOR1 in PASMCs were quantified with qRT-PCR. Meanwhile, the interaction among proteins were detected by Co-immunoprecipitation (Co-IP) assays. Cell proliferation and apoptosis was assessed by cell counting kit-8 assay(CCK-8), EdU incorporation and flow cytometry. Rat models of HPH were constructed to verify the role of DNA-PKcs in pulmonary vascular remodeling in vivo. Results DNA-PKcs protein levels were both significantly up-regulated in explants of pulmonary artery from HPH models and lung tissues of patients with hypoxemia. In human PASMCs, hypoxia up-regulated DNA-PKcs in a time-dependent manner. Downregulation of DNA-PKcs by targeted siRNA or small-molecule inhibitor NU7026 both induced cell proliferation inhibition and cell cycle arrest. DNA-PKcs affected proliferation by regulating NOR1 protein synthesis followed by the expression of cyclin D1. Co-immunoprecipitation of NOR1 with DNA-PKcs was severely increased in hypoxia. Meanwhile, hypoxia promoted G 2  + S phase, whereas the down-regulation of DNA-PKcs and NOR1 attenuated the effects of hypoxia. In vivo, inhibition of DNA-PKcs reverses hypoxic pulmonary vascular remodeling and prevented HPH. Conclusions Our study indicated the potential mechanism of DNA-PKcs in the development of HPH. It might provide insights into new therapeutic targets for pulmonary vascular remodeling and pulmonary hypertension.

Interleukin-17 (IL-17) plays an important role in cancer progression. Previous studies remained controversial regarding the correlation between IL-17 expression and lung cancer (LC) prognosis. To comprehensively and quantitatively summarize the prognostic value of IL-17 expression in LC patients, a systematic review and meta-analysis were performed. We identified the relevant literatures by searching the PubMed, EMBASE, Cochrane Library, SinoMed, China National Knowledge Infrastructure (CNKI) and Wanfang Data databases, up until April 1, 2017. Overall survival (OS), disease free survival (DFS) and clinicopathological characteristics were collected from relevant studies. Pooled hazard ratios (HR) and corresponding 95% confidence intervals (CI) were calculated to estimate the effective value of IL-17 expression on clinical outcomes. Six studies containing 479 Chinese LC patients were involved in this meta-analysis. The results indicated high IL-17 expression was independently correlated with poorer OS (HR = 1.82, 95% CI 1.44-2.29, P < 0.00001) and shorter DFS (HR = 2.41, 95% CI 1.42-4.08, P = 0.001) in LC patients. Further, when stratified by LC histological type (non-small cell lung cancer and small cell lung cancer), tumor stage (Ⅰ-Ⅲ,Ⅰ-Ⅳ and Ⅳ), detection specimen (serum, intratumoral tissue and pleural effusion), test method (immunological histological chemistry and enzyme linked immunosorbent assay), and HR estimated method (reported and estimated), all of the results were statistically significant. These data indicated that elevated IL-17 expression is correlated with poor clinical outcomes in LC. The meta-analysis did not show heterogeneity or publication bias. The present meta-analysis revealed that high IL-17 expression was an indicator of poor prognosis for Chinese patients with LC. It could potentially help to assess patients' prognosis and estimate treatment efficacy in therapeutic interventions.

Circular RNAs (circRNAs) are newly identified endogenous non-coding RNAs that function as crucial gene modulators in the development of several diseases. By assessing the expression levels of circRNAs in peripheral blood mononuclear cells (PBMCs) from patients with chronic obstructive pulmonary disease (COPD), this study attempted to find new biomarkers for COPD screening. We confirmed altered circRNA expression in PBMCs of COPD (n=41) vs controls (n=29). Further analysis focused on the highest and lowest circRNA expression levels. The -test is used to assess the statistical variances in circRNAs among COPD patients in the smoking and non-smoking cohorts. Additionally, among smokers, the Spearman correlation test assesses the association between circRNAs and clinical indicators. Two circRNAs, hsa_circ_0042590 and hsa_circ_0049875, that were highly upregulated and downregulated in PBMCs from COPD patients were identified and verified. Smokers with COPD had lower hsa_circ_0042590 and higher hsa_circ_0049875, in comparison to non-smokers. There was a significant correlation (r=0.52, P<0.01) between the number of acute exacerbations (AEs) that smokers with COPD experienced in the previous year and the following year (r=0.67, P<0.001). Moreover, hsa_circ_0049875 was connected to the quantity of AEs in the year prior (r=0.68, P<0.0001) as well as the year after (r=0.72, P<0.0001). AUC: 0.79, 95% CI: 0.1210-0.3209, P<0.0001) for hsa_circ_0049875 showed a strong diagnostic value for COPD, according to ROC curve analysis. Hsa_circ_0042590 showed a close second with an AUC of 0.83 and 95% CI: -0.1972--0.0739 (P <0.0001). This research identified a strong correlation between smoking and hsa_circ_0049875 and hsa_circ_0042590 in COPD PBMCs. The number of AEs in the preceding and succeeding years was substantially linked with the existence of hsa_circ_0042590 and hsa_circ_0049875 in COPD patients who smoke. Additionally, according to our research, hsa_circ_0049875 and hsa_circ_0042590 may be valuable biomarkers for COPD diagnosis.

PurposePlatinum-based doublet chemotherapy and radiotherapy are the standard treatment option in advanced squamous cell carcinoma patients. However, few agents could be selected for subsequent post-second-line treatment. As a small molecule inhibitor of vascular endothelial growth factor receptor-2 tyrosine kinase, apatinib had been proved in advanced gastric cancer. Here, we showed its efficacy and safety in lung squamous cell carcinoma.MethodsIn this retrospective study, 13 advanced lung squamous cell carcinoma patients were enrolled. They received doublet chemotherapy or docetaxel as the first-line treatment. After disease progressed, all patients were administrated apatinib monotherapy (250–425 mg/day) for second-line or fourth-line therapy.ResultsAfter apatinib monotherapy, two patients achieved partial response, four patients achieved stable disease, and seven patients achieved progression disease. The medium PFS was 3.1 months. The median OS had not yet been reached. The objective remission rate was 15.4% (2/13). The total disease control rate was 46.2% (6/13). The main advert effects were vomiting and hypertension.ConclusionApatinib might be an option as rescue treatment in advanced lung squamous cell carcinoma.

Azvudine (AZV), the first Chinese oral anti-coronavirus disease 2019 (COVID-19) drug, has shown substantial clinical benefits to viral clearance and prognosis in patients with mild and common COVID-19. However, there is no evidence in severe hospitalized COVID-19 patients. In this multicenter study, we analyzed 209 severe hospitalized COVID-19 patients in four hospitals. All the clinical data and the 28-day composite outcomes were recorded. All of the patients were categorized into two groups according to drug: the dexamethasone (DXM) group and the azvudine plus dexamethasone (AZV+DXM) group. There were no differences in sex, age, BMI, and underlying diseases between the two groups. The ratio of the 28-day composite outcome was lower for the AZV+DXM group than that for the DXM group (16.97% . 31.82%, = 0.029). The viral clearance time was shorter in the AZV+DXM group than in the DXM group (7.32 ± 2.57 . 8.55 ± 2.34 days, = 0.017). The PaO /FiO levels on day 5 (258.89 ± 55.22 . 233.12 ± 60.51, = 0.026) and day 10 (289.48 ± 44.09 . 261.52 ± 37.34, = 0.015) were higher in the AZV+DXM group than the DXM group. However, data on the hospitalization duration of the two groups were similar. Cox analysis showed the benefit of AZV+DXM in the subgroups of ≥65 years old, multiple organ dysfunction syndrome (MODS), cerebrovascular disease, C-reactive protein (CRP) ≥70mg/L, and D-dimer ≥1 µg/L. This study is the first to indicate that treatment with AZV+DXM might benefit severe Omicron-infected patients compared with DXM treatment alone. This finding demonstrates, at least partly, the necessity of antiviral treatment in severe patients.