Background Bronchiectasis (BE) is a chronic respiratory disease. Acute BE exacerbation caused by recurrent infections can lead to hemoptysis and even asphyxia, with high mortality and long hospitalization. This study aimed to identify novel diagnostic metabolic biomarkers for predicting acute exacerbation and severity of BE. Methods A liquid chromatography–mass spectrometry (LC–MS)-based untargeted metabolomic analysis was performed for serum samples from 45 patients with acute BE exacerbation and 15 healthy controls. The diagnostic value of the candidate metabolites was evaluated using receiver operating characteristic (ROC) curves. Results Based on bronchiectasis severity index (BSI) scores, patients with acute BE exacerbation were classified into mild, moderate, and severe BE groups. Compared to healthy controls, the abundance of 4-acetamidobutyric acid was elevated in the mild, moderate, and severe groups (p < 0.05), with no significant difference among the three groups. In the severe BE group, the abundances of taurochenodecoxycholic acid, oleamide, hexadecanamide, and glycodeoxycholic acid were significantly elevated from those in mild and moderate BE groups (p < 0.05), with Youden index (YI) ≥ 0.8 for all metabolites; the combination of these 4 metabolites had an area under the ROC curve (AUROC) of 0.99, a sensitivity of 100 % and a specificity of 93.3 % for identifying severe BE. Pathway analysis reveals that abnormally enriched metabolites in BE patients are associated with PI3K-Akt signaling pathway, mTOR signaling pathway, FoxO signaling pathway, renin-angiotensin system signaling pathway, asthma signaling pathway, and FcεRI signaling pathway, where prostaglandin D2 exerts direct or indirect impacts on these pathways. Conclusion 4-Acetamidobutyric acid can serve as a biomarker for predicting acute BE exacerbation, while taurochenodecoxycholic acid, oleamide, hexadecanamide, and glycodeoxycholic acid are robust biomarkers for predicting severe BE. Prostaglandin D2 plays a crucial role in promoting the pathogenesis of pulmonary inflammatory cell recruitment, cell autophagy, and pulmonary fibrosis during acute BE exacerbation. Overall, this study identifies biomarkers for predicting acute BE exacerbation and provides new targets for drug development.

Objective:To investigate the distribution differences in the respiratory tract microbiota of AECOPD patients in different BMI groups and explore its guiding value for treatment.Methods:Sputum samples of thirty-eight AECOPD patients were collected. The patients were divided into low, normal and high BMI group. The sputum microbiota was sequenced by 16S rRNA detection technology, and the distribution of sputum microbiota was compared. Rarefaction curve, α-diversity, principal coordinate analysis (PCoA) and measurement of sputum microbiota abundance in each group were performed and analyzed by bioinformatics methods.Results:1. The rarefaction curve in each BMI group reached a plateau. No significant differences were observed in the OTU total number or α-diversity index of microbiota in each group. PCoA showed significant differences in the distance matrix of sputum microbiota between the three groups, which was calculated by the Binary Jaccard and the Bray Curtis algorithm. 2. At the phylum level, most of the microbiota were Proteobacteria, Bacteroidetes Firmicutes, Actinobacteria, and Fusobacteria. At the genus level, most were Streptococcus, Prevotella, Haemophilus, Neisseria and Bacteroides. 3. At the phylum level, the abundance of Proteobacteria in the low group was significantly higher than that in normal and high BMI groups, the abundances of Firmicutes in the low and normal groups were significantly lower than that in high BMI groups. At the genus level, the abundance of Haemophilus in the low group was significantly higher than that in high BMI group, and the abundances of Streptococcus in the low and normal BMI groups were significantly lower than that in the high BMI group.Conclusions:1. The sputum microbiota of AECOPD patients in different BMI groups covered almost all microbiota, and BMI had no significant association with total number of respiratory tract microbiota or α-diversity in AECOPD patients. However, there was a significant difference in the PCoA between different BMI groups. 2. The microbiota structure of AECOPD patients differed in different BMI groups. Gram-negative bacteria (G-) in the respiratory tract of patients predominated in the low BMI group, while gram-positive bacteria (G+) predominated in the high BMI group.

Previously, we demonstrated the therapeutic effects of human umbilical cord mesenchymal stromal cells (hUC-MSCs) in severe coronavirus disease 2019 (COVID-19) patients. In this 3-month follow-up study, we examined discharged patients who had received hUC-MSC therapy to assess the safety of this therapy and the health-related quality of life (HRQL) of these patients. The follow-up cohort consisted of 28 discharged severe COVID-19 patients who received either the standard treatment (the control group) or the standard treatment plus hUC-MSC therapy. We examined liver function, kidney function, pulmonary function, coagulation, tumor markers, and vision. We also conducted electrocardiography (ECG) analysis, let the patients answer the St. George's Respiratory Questionnaire (SGRQ), and performed computed tomography (CT) imaging for assessing the lung changes. No obvious adverse effects were observed in the hUC-MSC group after 3 months. Measurements of blood routine index, C-reactive protein and procalcitonin, liver and kidney function, coagulation, ECG, tumor markers, and vision were almost within the normal ranges in both the treatment and control groups. Forced expiratory volumes in 1 s (FEV1) (% of predicted) were 71.88% +/- 8.46% and 59.45% +/- 27.45% in the hUC-MSC and control groups (P < 0.01), respectively, and FEV1/forced vital capacity (FEV1/FVC) ratios were 79.95% +/- 8.00% and 58.97% +/- 19.16% in the hUC-MSC and control groups, respectively (P < 0.05). SGRQ scores were lower in the hUC-MSC group than in the control group (15.25 +/- 3.69 vs. 31.9 +/- 8.78, P < 0.05). The rate of wheezing in the hUC-MSC group was also significantly lower than that in the control group (37.5% vs. 75%, P < 0.05). There were no significant differences in CT scores between the two groups (0.60 +/- 0.88 vs. 1.00 +/- 1.31, P = 0.917). Overall, the intravenous transplantation of hUC-MSCs accelerated partial pulmonary function recovery and improved HRQL, indicating relative safety and preliminary efficacy of this treatment for patients with severe COVID-19.

目的:回顾性分析中小剂量糖皮质激素在重症新型冠状病毒肺炎(corona virus disease-2019,COVID-19)患者治疗中的作用.方法:回顾性分析2020年2月15日-3月20日南京医科大学附属逸夫医院援黄石医疗队在黄石市中医医院收治的95例重症COVID-19患者的临床资料,根据是否使用糖皮质激素分为对照组(常规治疗,33例)和激素治疗组(常规治疗联合糖皮质激素治疗,62例),比较两组的实验室检查结果、临床症状缓解时间、28 d死亡率、重症向危重症转变率、住院天数、炎症指标、氧合指数改善、影像学改变以及不良反应的发生情况.结果:一般临床资料中,激素治疗组的淋巴细胞计数及单核细胞计数明显低于对照组(P＜0.05),其余基线临床资料两组无明显差异.与对照组相比,激素治疗组临床症状缓解时间明显缩短[9.50(5.00,14.50)dvs.16.00(5.00,21.00)d,P＜0.001],重症/危重症转换率明显下降[12.90％ vs.33.33％,P=0.029],住院天数明显缩短[20.00(16.00,22.00)d vs.24.00(20.50,26.50)d,P=0.002],28 d死亡率未见明显升高[6.45％ vs.9.09％,P=0.691],氧合指数恢复明显增快,炎症因子C反应蛋白、白介素-6下降幅度明显增大,影像学吸收速度明显增快,两组间不良反应无明显差别.结论:中小剂量糖皮质激素能显著缩短重症COVID-19患者临床症状缓解时间,改善氧合,促进肺部病变吸收,且没有明显不良反应,在重症COVID-19治疗过程中可以短疗程使用.

目的 分析慢性阻塞性肺疾病(COPD)患者血清多配体蛋白聚糖-1(SDC-1)、血管生成素样蛋白4(ANGPTL4)及颗粒蛋白前体(PGRN)与肺功能及炎性反应的相关性.方法 选取2017年2月—2019年12月南京医科大学附属逸夫医院呼吸内科收治COPD患者150例作为研究对象,按病情分为急性加重期组88例及稳定期组62例,另选取同期于医院进行体检的健康志愿者60例作为健康对照组.检测并比较3组血清SDC-1、ANGPTL4、PGRN、炎性因子水平及肺功能指标,分析COPD患者血清SDC-1、ANGPTL4、PGRN与血清炎性因子及肺功能指标的相关性.结果 急性加重期组及稳定期组的血清SDC-1、ANGPTL4及PGRN水平均高于健康对照组,且急性加重期组上述指标水平均高于稳定期组(F=10.485、13.275、7.195,P均<0.01).急性加重期组及稳定期组的第1秒用力呼气容积(FEV1)、用力肺活量(FVC)、FEV1/FVC均低于健康对照组,且急性加重期组上述指标水平低于稳定期组(F/P=8.274/0.000、6.274/0.010、8.975/0.000).急性加重期组及稳定期组的血清肿瘤坏死因子-α(TNF-α)、白介素-8(IL-8)及IL-17水平均高于健康对照组,且急性加重期组上述指标水平均高于稳定期组(F=20.853、33.285、16.823,P<0.000).COPD患者血清SDC-1、ANGPTL4及PGRN水平与FEV1、FVC、FEV1/FVC均呈负相关,与血清TNF-α、IL-8、IL-17均呈正相关(P均<0.01).结论 COPD患者血清SDC-1、ANGPTL4及PGRN存在明显高表达,在急性加重期患者中升高更加明显,且随着上述血清指标水平的升高,肺功能越差,炎性反应越严重.

Previously, we demonstrated the therapeutic effects of human umbilical cord mesenchymal stromal cells (hUC-MSCs) in severe coronavirus disease 2019 (COVID-19) patients. In this three-month follow-up study, we examined discharged patients who had received hUC-MSC therapy to assess the safety of this therapy and the health-related quality of life (HRQL) of these patients. The follow-up cohort consisted of 28 discharged severe COVID-19 patients who received either the standard treatment (the control group) or the standard treatment plus hUC-MSC therapy. We examined liver function, kidney function, pulmonary function, coagulation, tumor markers, and vision. We also conducted electrocardiography (ECG) analysis, let the patients answer the St. George's Respiratory Questionnaire (SGRQ), and performed computed tomography (CT) imaging for assessing the lung changes. No obvious adverse effects were observed in the hUC-MSC group after three months. Measurements of blood routine index, C-reactive protein and procalcitonin, liver and kidney function, coagulation, ECG, tumor markers, and vision were almost within the normal ranges in both the treatment and control groups. Forced expiratory volumes in 1 s (FEV1) (% of predicted) were 71.88±8.46% and 59.45±27.45% in the hUC-MSC and control groups (P<0.01), respectively, and FEV1/forced vital capacity (FEV1/FVC) ratios were 79.95±8.00% and 58.97±19.16% in the hUC-MSC and control groups, respectively (P<0.05). SGRQ scores were lower in the hUC-MSC group than in the control group (15.25±3.69 vs. 31.9±8.78, P<0.05). The rate of wheezing in the hUC-MSC group was also significantly lower than that in the control group (37.5% vs. 75%, P<0.05). There were no significant differences in CT scores between the two groups (0.60±0.88 vs. 1.00±1.31, P=0.917). Overall, the intravenous transplantation of hUC-MSCs accelerated partial pulmonary function recovery and improved HRQL, indicating the relatively safety and preliminary efficacy of this treatment for patients with severe COVID-19.

To report the clinical characteristics and potential risk factors of patients with coronavirus disease 2019 (COVID-19) in Wuhan Stadium Cabin Hospital in Hubei Province. A total of 571 patients of COVID-19 treated in the Wuhan Stadium Cabin Hospital were selected for analysis, univariable and multivariable logistic regression methods were used to explore the risk factors associated with disease aggravation. The main clinical symptoms of moderate COVID-19 were fever, cough and dyspnea, hypertension, diabetes, and coronary heart diseases were the main comorbidities both in transferred and stable patients. Twenty-six patients (4.55%) of mild and moderate patients had disease aggravation, and most of which occurred between 36 and 48 hours after admission. Multiple regression analysis showed increasing odds of disease aggravation associated with former smoker history, diabetes, dyspnea, consolidation, and interstitial abnormalities of computed tomography scanning, lymphopenia and elevated of C-reactive protein, the time points of transferred patients mainly between 36 and 48 hours (65.38%), and the average hospital stay for stable patients was 15 days.It could help clinicians to identify patients with poor prognosis at an early stage, and provide early warning role for timely intervention.

Background: COVID-19 is a highly infectious respiratory disease. No therapeutics have yet been proven effective for treating severe COVID-19. Objectives: To determine whether human umbilical cord mesenchymal stem cell infusion may be effective and safe for the treatment of severe COVID-19. Methods: Patients with severe COVID-19 were randomly divided into 2 groups: the standard treatment group and the standard treatment plus hUC-MSC infusion group. The incidence of progression from severe to critical illness, 28-day mortality, clinical symptom improvement, time to clinical symptom improvement, hematologic indicators including C-reactive protein, lymphocyte number, and interleukin 6, and imaging changes were observed and compared between the two groups. Measurements and Main Results: The incidence of progression from severe to critical illness and the 28-day mortality rate were 0 in the hUC-MSC treatment group, while 4 patients in the control group deteriorated to critical condition and received invasive ventilation; 3 of them died, and the 28-day mortality rate was 10.34% . In the hUC-MSC treatment group, the time to clinical improvement was shorter than that in the control group. Clinical symptoms of weakness and fatigue, shortness of breath, and low oxygen saturation obviously improved beginning on the third day of stem cell infusion and reached a significant difference on day 7. CRP and IL-6 levels were significantly lower from day 3 of infusion, the time for the lymphocyte count to return to the normal range was significantly faster, and lung inflammation absorption was significantly shorter on CT imaging in the hUC-MSC group than in the control group. Conclusions: Intravenous transplantation of hUC-MSCs is a safe and effective method that can be considered a salvage and priority treatment option for severe COVID-19.

Background : Many of severe COVID-19 patients are admitted to the hospital or even to the Intensive Care Unit(ICU). The present study was aimed to investigated the risk factors in death from COVID-19. Methods : In this retrospective study, all inpatients confirmed severe or critical COVID-19 from two tertiary hospital in Huangshi were included, who had been discharged or died by March19,2020. Demographic,clinical,treatment,laboratory data and information were extracted from electronic medical records and compared between survivors group and non-survivors group. The univariable and multivariable logistic regression analysis was used to analyze the risk factors associated with in-hospital death. Results : 81 patients were included in this study, of whom 55 were discharged and 26 died in hospital. In all patients, 36(44.4%) patients had comorbidity, including hypertension(27[33.3%]), diabetes(11[13.6%]) and coronary heart disease (CHD)(11[13.6%]), and 16(19.8%) patients accompanied with more than 2 kinds of underlying diseases. The proportion of CHD in non-survivors group was significantly higher than that in survivors group(26.9% vs 7.3%, P=0.032), but there were no differences in hypertension, diabetes and COPD between the non-survivors group and the survivors group. Multivariable logistic regression analysis showed increasing odds of in-hospital death associated with aspartate aminotransferase(AST) and invasive mechanical ventilation (IMV) (P<0.001)(P=0.017）. Conclusions: Invasive Mechanical Ventilation may contribute to mortality of severe/critical COVID-19 pneumonia, and with higher AST at admission was one of the indicators of poor prognosis. Trial registration: Chinese Clinical Trial Registration; ChiCTR2000031494; Registered 02 April 2020; http:// www.medresman.org

Background: In order to report the clinical characteristics of COVID-19 Patients in Wuhan Stadium Cabin Hospital in Hubei Province. Methods: A total of 545 patients with mild and moderate types of coronavirus pneumonia (COVID-19) treated in the Wuhan Stadium Cabin Hospital were selected from Feb 13 to Feb 29, 2020, and their general information, epidemiological history, incidence, clinical manifestations, laboratory tests, and imaging data, treatment and prognosis were collected for analysis. Finding: The total 545 patients were from 11 to 78 years old, with a median age of 50 years, 264 males (48.44%) and 281 females (51.56%), there were 423 cases (77.61%) with no smoking history, 122 cases (22.39%) with a history of smoking. The main clinical symptoms were fever and cough, which accounted for 284 (51.92%) and 382 cases (70.09%), the other symptoms included 77 cases (14.77%) of fatigue and muscle aches, 89 cases (16.27%) of dyspnea, 95 cases (17.37%) of chest tightness, 52 cases (9.51%) of headache, diarrhea was uncommon, only 49 cases (8.96%). On admission, ground-glass opacity was the most common radiologic finding from chest computed tomography (CT) scanning (50.64%), 108 cases (19.82%) had no abnormal density shadow, 29 cases (5.32%) had consolidation, 87 cases (15.96%) had nodular lesion, and 45 cases (8.25%) had interstitial abnormalities. Lymphocytopenia was present in 403 cases (73.94%) of the patients on admission, and C-reactive protein had a slight elevated in 543 cases (99.63%). Up to now, 468 cases (85.77%) were discharged from the hospital, and no patient died, the average hospital stay for discharge patients was 15 days. Interpretation: Covid-19 is a highly infectious disease, and mostly are middle-aged and elderly cases, there is no significant difference between males and females. Fever, cough, and fatigue are most the clinical manifestations. Blood tests suggest that white blood cells are most normal and lymphocytes are reduced, C-reactive protein is slightly elevated, and imaging findings are of guiding significance for diagnosis of the disease and therapeutic effect. At the same time of antiviral treatment, pay attention to nutritional support and gastrointestinal function protection, combined with traditional Chinese medicine treatment is very important. Early diagnosis, isolation, and treatment are essential and critical to control the disease. Cabin hospital, as a fast and effective method for centralized isolation and treatment of patients with infectious diseases, can provide a valuable experience in dealing with public emergency incident.Funding Statement: None.Declaration of Interests: Lei Shu, Xiaoyan Wang, Xiaolin Chen, Mingquan Li, Lei Shi, Mingjing Wu, Kaili Deng, Jing Wei, Xueli Wang, Yang Cao, Jiaxin Yan, Ganzhu Feng declared that there were no competing interests. Ethics Approval Statement: The study was approved by the Ethics Committee of Wuhan Stadium Cabin Hospital, and the written informed consent was waived because of the retrospective nature of the study and belongs to emergency medical service.