Path to normality: Assessing the level of social-distancing measures relaxation against antibody-resistant SARS-CoV-2 variants in a partially-vaccinated population.

Introduction: Two years into the coronavirus 2019 (COVID-19) pandemic, populations with less built-up immunity continued to devise ways to optimize social distancing measures (SDMs) relaxation levels for outbreaks triggered by SARS-CoV-2 and its variants to resume minimal economics activities while avoiding hospital system collapse. Method: An age-stratified compartmental model featuring social mixing patterns was first fitted the incidence data in second wave in Hong Kong. Hypothetical scenario analysis was conducted by varying population mobility and vaccination coverages (VCs) to predict the number of hospital and intensive-care unit admissions in outbreaks initiated by ancestral strain and its variants (Alpha, Beta, Gamma, Delta and Omicron). Scenarios were "unsustainable" if either of admissions was larger than the maximum of its occupancy. Results: At VC of 65%, scenarios of full SDMs relaxation (mean daily social encounters prior to COVID-19 pandemic = 14.1 contacts) for outbreaks triggered by ancestral strain, Alpha and Beta were sustainable. Restricting levels of SDMs was required such that the optimal population mobility had to be reduced to 0.9, 0.65 and 0.37 for Gamma, Delta and Omicron associated outbreaks respectively. VC improvement from 65% to 75% and 95% allowed complete SDMs relaxation in Gamma-, and Delta-driven epidemic respectively. However, this was not supported for Omicron-triggered epidemic. Discussion: To seek a path to normality, speedy vaccine and booster distribution to the majority across all age groups is the first step. Gradual or complete SDMs lift could be considered if the hybrid immunity could be achieved due to high vaccination coverage and natural infection rate among vaccinated or the COVID-19 case fatality rate could be reduced similar to that for seasonal influenza to secure hospital system sustainability.

Toll-Like Receptor 2 (TLR2) and TLR4 Mediate the IgA Immune Response Induced by Mycoplasma hyopneumoniae.

IgA plays an important role in mucosal immunity against infectious pathogens; however, the molecular mechanism of IgA secretion in response to infection remains largely unknown, particularly in Mycoplasma spp. In this study, we found that the levels of IgA in the peripheral blood serum, bronchoalveolar lavage fluid, nasal mucosa, trachea, hilar lymph nodes, and lung tissues of pigs increased significantly after infection with Mycoplasma hyopneumoniae Furthermore, IgA and CD11c were detected in the lungs and hilar lymph nodes by immunohistochemical analysis, and colocalization of these two markers indicates that CD11c+ cells play an important role in IgA mucosal immunity induced by M. hyopneumoniae To investigate the regulatory mechanism of IgA, we separated mouse dendritic cells (DCs) from different tissues and mouse macrophages from the lungs and then cultured mouse B cells together with either DCs or macrophages in vitro In the mouse lung-DC/B (LDC/B) cell coculture, IgA secretion was increased significantly after the addition of whole-cell lysates of M. hyopneumoniae The expression of both Toll-like receptor 2 (TLR2) and TLR4 was also upregulated, as determined by mRNA and protein expression analyses, whereas no obvious change in the expression of TLR3 and TLR7 was detected. Moreover, the IgA level decreased to the same as the control group when TLR2 or TLR4 was inhibited instead of TLR8 or TLR7/9. In conclusion, M. hyopneumoniae can stimulate the response of IgA through TLR2 and TLR4 in a mouse LDC/B cell coculture model, and the coculture model is an ideal tool for studying the IgA response mechanism, particularly that with Mycoplasma spp.

Apatinib Plus Chemotherapy Shows Clinical Activity in Advanced NSCLC: A Retrospective Study.

Apatinib is an oral TKI with antiangiogenic properties, and it is currently approved for the treatment of advanced gastric cancer in China. This agent has also been tested in other human solid tumors, including non-small cell lung cancer (NSCLC). Since the combination of chemotherapy and an antiangiogenic agent has been shown to be a feasible strategy in NSCLC, it is conceivable that a similar approach combining apatinib with chemotherapy may yield clinical activity. With this in mind, we investigated the efficiency of apatinib in combination with pemetrexed or docetaxel in advanced NSCLC. We treated a total of 20 patients with metastatic NSCLC adenocarcinoma with apatinib in combination with either pemetrexed or docetaxel from January 2016 to March 2017. The performance status of these patients was 0 or 1. All of these patients had been previously treated with two or more lines of treatment and had experienced disease progression prior to study enrollment. The overall objective response rate (ORR) was 30%, with 6 patients who had partial response (PR), 10 patients who had stable disease (SD), and 4 patients who had progressive disease (PD). The main adverse events were skin rash, hypertension, palmar-plantar erythrodysesthesia syndrome, diarrhea, and fatigue. Nearly 30% of patients required interruption of treatment as a result of toxicity. Our study demonstrated that apatinib combined with systemic cytotoxic chemotherapy has clinical efficacy in patients with disease-refractory metastatic NSCLC and provides evidence for further studies investigating apatinib-based combination regimens.

Clinical characteristics of patients with chronic obstructive pulmonary disease overlapped with bronchial asthma.

BACKGROUND: The clinical characteristics of patients with chronic obstructive pulmonary disease overlapped with bronchial asthma (COPD-BA) have not been discussed thoroughly. OBJECTIVE: To reveal the clinical features of patients with COPD-BA, to evaluate the risk factors of COPD-BA, and to provide suggestions for COPD individualized therapy. METHODS: A retrospective observational study was performed. A total of 182 patients with COPD (90 with COPD-BA and 92 with pure COPD) were recruited in the study. Information on the following items was collected: demographics, clinical manifestations, complications, laboratory findings, other histories, and inpatient treatments during exacerbation. RESULTS: A total of 182 patients were diagnosed with COPD, with 90 (49.45%) being classified as having COPD-BA. Patients with COPD-BA were more likely to be female (P = .004) and experienced more severe respiratory exacerbations (P = .04) despite being younger (P = .008). Those patients at onset of recurrent cough and sputum production were younger (P = .001). Significantly, a positive asthmatic family history (P = .03) was observed. Patients with COPD-BA usually had higher level of total serum IgE (although no differences were observed), had higher positive rates of the serum specific IgE (P = .004), and were more like to have an allergic history (P = .003). Allergic factor was the risk factor of COPD-BA (odds ratio, 4.477). During hospitalization, patients with COPD-BA tended to be treated with systemic corticosteroids (P = .008). CONCLUSION: Patients with COPD-BA were characterized by persistent airflow limitation with unique clinical features. Allergic factor was associated with the presence of asthmatic characteristics in patients with COPD. When hospitalized for exacerbation, the individualized therapy for COPD-BA might include the use of corticosteroids systemically.