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While SARS-CoV-2 pathogenesis has been intensively investigated, the host mechanisms of viral clearance and inflammation resolution are still elusive because of the ethical limitation of human studies based on COVID-19 convalescents. Here we infected Syrian hamsters by authentic SARS-CoV-2 and built an ideal model to simulate the natural recovery process of SARS-CoV-2 infection from severe pneumonia1,2. We developed and applied a spatial transcriptomic sequencing technique with subcellular resolution and tissue-scale extensibility, i.e., Stereo-seq3, together with single-cell RNA sequencing (scRNA-seq), to the entire lung lobes of 45 hamsters and obtained an elaborate map of the pulmonary spatiotemporal changes from acute infection, severe pneumonia to the late viral clearance and inflammation resolution. While SARS-CoV-2 infection caused massive damages to the hamster lungs, including naive T cell infection and deaths related to lymphopenia, we identified a group of monocyte-derived proliferating Slamf9+Spp1+ macrophages, which were SARS-CoV-2 infection-inducible and cell death-resistant, recruiting neutrophils to clear viruses together. After viral clearance, the Slamf9+Spp1+ macrophages differentiated into Trem2+ and Fbp1+ macrophages, both responsible for inflammation resolution and replenishment of alveolar macrophages. The existence of this specific macrophage subpopulation and its descendants were validated by RNAscope in hamsters, immunofluorescence in hACE2 mice, and public human autopsy scRNA-seq data of COVID-19 patients. The spatiotemporal landscape of SARS-CoV-2 infection in hamster lungs and the identification of Slamf9+Spp1+ macrophages that is pivotal to viral clearance and inflammation resolution are important to better understand the critical molecular and cellular players of COVID-19 host defense and also develop potential interventions of COVID-19 immunopathology.
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Objective:To observe the clinical characteristics and guideline compliance of chronic obstructive pulmonary disease (COPD) patients with initial triple therapy in real-life world.Methods:This study is a cross-sectional study. The subjects of the study were COPD patients admitted to 13 hospitals in Hunan Province and Guangxi Zhuang Autonomous Region from December 2016 to December 2021. The initial treatment was triple inhaled drugs. The data collected included gender, age, diagnosis, body mass index (BMI), history of acute exacerbation (AE) in the past year, pulmonary function, COPD Assessment Test (CAT) score, modified British Medical Research Council Dyspnea Questionnaire (mMRC), inhaled drugs and other indicators. The characteristics and differences of COPD patients before and after 2020 were analyzed.Results:7 184 patients with COPD were enrolled in this study, including 2 409 COPD patients treated with initial triple therapy, accounting for 33.5%(2 409/7 184). Taking January 1st, 2020 as the cut-off point, 1 825 COPD patients (75.8%) received initial treatment with triple inhaled drugs before 2020 and 584 patients (24.2%) after 2020 were included in this study. Compared with COPD patients before 2020, the COPD patients after 2020 had higher FEV 1% [(40.9±15.5 )% vs (39.3±15.5)%, P=0.040], lower CAT [(15.8±6.5)point vs (17.5±6.2)point, P<0.001], less AE in the past year [1(0, 2)times vs 1(0, 2)times, P=0.001] and higher rate of non-AE [255(43.7%) vs 581(37.1%), P=0.006]. In addition, before 2020, patients with COPD were mainly treated with open triple drugs (1 825/1 825, 100%); after 2020, 306 patients (52.4%) received open triple inhaled drugs, and 278 patients (47.6%) received closed triple inhaled drugs. Conclusions:In real-life world, most of patients with COPD treated with triple therapy have severe lung function, obvious symptoms and high risk of acute exacerbation. The real-world prescribing of triple therapy in patients with COPD does not always reflect recommendations in guidelines and strategies, and overtreatment is common. After 2020, prescribing triple therapy for COPD patients is more positive and worse consistency with guideline.
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A few animals have been suspected to be intermediate hosts of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, a large-scale single-cell screening of SARS-CoV-2 target cells on a wide variety of animals is missing. Here, we constructed the single-cell atlas for 11 representative species in pets, livestock, poultry, and wildlife. Notably, the proportion of SARS-CoV-2 target cells in cat was found considerably higher than other species we investigated and SARS-CoV-2 target cells were detected in multiple cell types of domestic pig, implying the necessity to carefully evaluate the risk of cats during the current COVID-19 pandemic and keep pigs under surveillance for the possibility of becoming intermediate hosts in future coronavirus outbreak. Furthermore, we screened the expression patterns of receptors for 144 viruses, resulting in a comprehensive atlas of virus target cells. Taken together, our work provides a novel and fundamental strategy to screen virus target cells and susceptible species, based on single-cell transcriptomes we generated for domesticated animals and wildlife, which could function as a valuable resource for controlling current pandemics and serve as an early warning system for coping with future infectious disease threats.
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Objective To observe the therapeutic efficacy and safety of recombinant tissue plasminogen activator (rt-PA) for treatment of patients with acute cerebral infarction and investigate the prognostic factors of thrombolysis. Methods The clinical data of 60 patients with acute cerebral infarction from January 2009 to November 2013 in Department of Emergency, Hangzhou Traditional Chinese Medicine Hospital were retrospectively analyzed;of them, 30 cases received intravenous rt-PA thrombolytic treatment, being in the thrombolytic group, 0.9 mg/kg rt-PA was given to the patient within 4.5 hours after the disease onset, the total dosage could not exceed 90 mg, in which 10%was intravenously injected and the rest 90%was intravenously dripped slowly within 60 minutes. That another 30 cases did not undergo thrombolytic therapy was assigned as the control group, and they took aspirin, etc anti-platelet aggregation routine treatment. Before and after thrombolytic treatment for 1 hour, 24 hours and 14 days, the National Institutes of Health Stroke Scale (NIHSS) score was evaluated in the two groups;before and after thrombolytic therapy for 0.5, 1.0, and 1.5 hours, the patient's scores of Barthel index (BI) were observed in the two groups. In thrombolytic group, the situations of hemorrhage transformation, symptomatic hemorrhage and modified Rankin scale (mRS) score in 3 months of the patients with different ages, complications and NIHSS scores were observed. Results Before treatment, no statistically significant differences were found in the NIHSS score (15.2±3.6 vs. 15.5±3.3) and BI score (45.0±8.8 vs. 44.1±7.6) between the control group and thrombolytic group (both P>0.05);after treatment with the extension of time, the NIHSS score was gradually reduced, reaching the lowest level on the 14th day after thrombolytic treatment, while the BI score was gradually increased, reaching its peak at 1.5 hours after thrombolytic treatment, the changes being more prominent in thrombolytic group (NIHSS score:9.7±2.6 vs. 12.8±4.2, BI score:82.6±7.8 vs. 69.6±9.8, both P80 years old was higher than that in cases≤80 years old (15 vs. 12); the age (years: 71.0±4.1 vs. 61.5±2.6), baseline NIHSS score (14 vs. 11) and bleeding conversion rate [37.50% (3/8) vs. 18.18% (4/22)] of cases with atrial fibrillation were higher than those not complicated with atrial fibrillation; the NIHSS score of cases with elevated international normalized ratio (INR) was lower than those without elevated INR (11 vs. 14);The bleeding conversion rate [16.67%(1/6) vs. 29.17%(7/24)] with NIHSS score≤4 were lower than those with NIHSS score>4;the mRS score in 3 months (4 vs. 2), and percentage of 3-month mRS score≤2 [11.1%(1/9) vs. 52.38%(11/21)] in cases with NIHSS score≥20 was higher than that in cases with NIHSS score<20 (all P<0.05). The fatality rate of two groups was 3.33%. Conclusions The intravenous rt-PA thrombolytic treatment can significantly promote the early recovery of neurologic impairment for patients with acute cerebral infarction. The therapy can improve the prognosis and its safety is relatively good. Meanwhile it is similarly effective for cases over 80, with complications such as atrial fibrillation, raised INR, and with different degrees of severity.
