BackgroundCurrently, as the omicron variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) surges amid the coronavirus disease 2019 (COVID-19) pandemic, its clinical characteristics with intrinsic severity and the protection from vaccination have been understudied.MethodsWe reported 169 COVID-19 patients that were infected with the omicron variant of SARS-CoV-2 and hospitalized in Suzhou, China, from February to March 2022, with their demographic information, medical/immunization history, clinical symptom, and hematological profile. At the same time, patients with none/partial (one-dose), full (two-dose) and three–dose vaccination were also compared to assess the vaccine effectiveness.FindingsFor the omicron COVID-19 patients included in this study, their median age was 33.0 [interquartile range (IQR): 24.0–45.5], 53.3% were male and the median duration from illness onset to hospitalization was 2 days. Hypertension, bronchitis, and diabetes were the leading comorbidities among patients. While the common clinical symptoms included cough, fever, expectoration, and fatigue, etc., asymptomatic patients took up a significant portion (46.7%). For hematological parameters, most values revealed the alleviated pathogenicity induced by the omicron variant infection. No critically ill or deceased patients due to COVID-19 infection were reported in this study.InterpretationOur results supported that the viremic effect of the omicron variant became milder than the previous circulating variants, while full vaccination or booster shot was greatly desired for an effective protection against clinical severity.

Critically ill hospitalized H7N9 patients experienced a higher rate of cardiac complications than did patients with 2009 pandemic H1N1 influenza virus infections, with the exception of pericardial effusion. This study may help in the prevention, identification, and treatment of influenza-induced cardiac complications in both pandemic H1N1 influenza virus and H7N9 infections.

Radiotherapy is the common treatment of choice for locally advanced lung cancer, but the radioresistance of lung cancer remains a significant therapeutic obstacle. We previously demonstrated that adenovirus-mediated inhibitor of growth 4 (ING4) tumor suppressor gene delivery (AdVING4) can chemosensitize human hepatocarcinoma cells to anticancer drug cisplatin (CDDP). However, its radiosensitizing effects in cancer therapy are largely elusive. In the present study, we investigated the therapeutic efficacy of AdVING4 gene therapy combined with ionizing radiotherapy for SPC-A1 human non-small-cell lung cancer (NSCLC) cells in vitro and in vivo in athymic nude mice, and also elucidated its underlying mechanisms. We found that AdVING4 gene therapy plus radiotherapy induced synergistic tumor suppression and apoptosis in in vitro SPC-A1 human NSCLC cells and in vivo SPC-A1 xenografted tumors s.c. implanted in athymic nude mice. Mechanistically, AdVING4 combined with radiation resulted in a substantial upregulation of Bax, Fas, FasL and Cleaved Caspase-3, and downregulation of Bcl-2 in SPC-A1 human NSCLC xenografted tumors. In addition, AdVING4 plus radiation synergistically reduced the tumor vessel CD34 expression and microvessel density (MVD) in vivo. Most importantly, AdVING4 potentially blocked the radiation-induced enhancement of cyclooxygenase-2 and survivin radioresistant factors, and vascular endothelial growth factor and IL-8 proangiogenic factors. The enhanced antitumor effects elicited by AdVING4 plus radiotherapy were closely associated with the cooperative activation of intrinsic and extrinsic apoptotic pathways, and synergistic inhibition of tumor angiogenesis. Thus, our results suggested that AdVING4 combined with radiotherapy may be a feasible and effective strategy for treatment of radioresistant NSCLC and other cancers.

Increasing evidence has indicated the roles of sirtuin 7 (SIRT7) in numerous human cancers. However, the effects and the clinical significance of SIRT7 in human lung cancer is largely unknown. The present research demonstrated that SIRT7 was increased in human lung cancer tumor tissues. SIRT7 upregulation was associated with clinicopathological characteristics of lung cancer malignancy including positive lymph node metastasis, high pathologic stage and large tumor size. SIRT7 was also upregulated in human non-small cell lung cancer (NSCLC) cell lines. Furthermore SIRT7-overexpressed A549 (A549-SIRT7) and SIRT7-knocked down H292 (H292-shSIRT7) human NSCLC cell lines were established. Using these NSCLC cells and xenograft mouse models, it was revealed that SIRT7 overexpression markedly promoted growth and G1 to S cell cycle phase transition as well as migration, invasion and distant lung metastasis in A549 NSCLC cells, whereas SIRT7 knockdown suppressed these processes in H292 NSCLC cells. Mechanistically, in A549 NSCLC cells, SIRT7 overexpression significantly activated not only protein kinase B (AKT) signaling but also extracellular signal-regulated kinase 1/2 (ERK1/2) signaling. SIRT7 overexpression also significantly downregulated cyclin-dependent kinase (CDK) inhibitors including p21 and p27 as well as upregulated cyclins including cyclin D1 and cyclin E1, and CDKs including CDK2 and CDK4. Notably, the epithelial-mesenchymal transition (EMT) process of A549 NSCLC cells was facilitated by SIRT7 overexpression, as evidenced by E-cadherin epithelial marker downregulation and mesenchymal markers (N-cadherin, vimentin, Snail and Slug) upregulation. In addition, SIRT7 knockdown in H292 NSCLC cells exhibited the opposite regulatory effects. Moreover, inhibition of AKT signaling abated the promoting effects of SIRT7 in NSCLC cell proliferation and EMT progression. The present data indicated that SIRT7 accelerated human NSCLC cell growth and metastasis possibly by promotion of G1 to S-phase transition and EMT through modulation of the expression of G1-phase checkpoint molecules and EMT markers as well as activation of AKT and ERK1/2 signaling. SIRT7 could be an innovative potential target for human NSCLC therapy.

A recent study from our group demonstrated that the Ca-sensing receptor (CaSR) was upregulated and that the extracellular Ca-induced increase in the cytosolic Ca concentration [Ca] was enhanced in pulmonary arterial smooth muscle cells (PASMCs) from patients with idiopathic pulmonary arterial hypertension. Here, we examined whether hypoxia-induced activation of Notch signaling leads to the activation and upregulation of CaSR in hypoxia-induced pulmonary hypertension (HPH). The activation of Notch signaling with Jag-1, a Notch ligand, can activate the function and increase the expression of CaSR in acute and chronic hypoxic PASMCs. Downregulation of Notch3 with a siRNA attenuates the extracellular Ca-induced increase in [Ca] and the increase in hypoxia-induced PASMC proliferation in acute hypoxic rat PASMCs. Furthermore, we tested the prevention and rescue effects of a γ-secretase inhibitor (DAPT) in HPH rats. For the Jag-1-treated group, right ventricular systolic pressure (RVSP), right heart hypertrophy (RV/LV+S ratio), and the level of right ventricular myocardial fibrosis were higher than the hypoxia alone group. Meanwhile, DAPT treatment prevented and rescued pulmonary hypertension in HPH rats. The Notch activation of CaSR mediates hypoxia-induced pulmonary hypertension. Understanding the new molecular mechanisms that regulate [Ca] and PASMC proliferation is critical to elucidating the pathogenesis of HPH and the development of novel therapies for pulmonary hypertension.