Search

Background Pulmonary lymphoepithelioma-like carcinoma (PLELC) is a rare subtype of lung cancer that is less reported and not well-understood. Materials and Methods We investigated the clinical features of 85 patients with PLELC to determine the prognostic factors. Results PLELC preferentially affected the young (71.8%) and nonsmokers (72.9%), without a significant difference in gender. Most (50.6%) patients were at the early stage with opportunity for operation, and patients at advanced stages mainly received multimodality treatment. The median follow-up duration was 17 months (range, 1-39 months) for the whole group, and the 3-year overall survival rate for patients in the early stage was 100%, whereas the 1-year and 2-year overall survival rate for patients in the advanced stage were 93% and 77%, respectively. The tumor stages (P = .031), distant lymph node metastasis (P = .035) and performance status (P = .008) were associated with progression-free survival in the univariate analysis, whereas performance status was an independent prognostic factor in the multivariate analysis (P = .016). The median progression-free survival in the paclitaxel plus platinum (12 months) group and gemcitabine plus platinum (10 months) group were significantly longer than that in the pemetrexed plus platinum (5 months) group (P = .001). Conclusion PLELC had a better prognosis compared with other types of non–small-cell lung cancer and was sensitive to radiotherapy and chemotherapy. Gemcitabine plus platinum and paclitaxel plus platinum should be used as first-line treatment of PLELC, whereas the second-line treatment, if necessary, was always decided by the managing oncologist. The tumor stages and performance status were predictive in the prognosis of patients with PLELC.

Multiple studies have addressed the vital role of Nod-like receptor protein 3(NLRP3)/caspase-1/IL-1β signaling in asthma. Yet, the role of NLRP3/caspase-1 in toluene diisocyanate (TDI)-induced asthma is still obscure. The aim of this study is to investigate the role of the NLRP3/caspase-1 axis in TDI-induced asthma. Using an established murine model of TDI-induced asthma as described previously, we gave the asthmatic mice a highly selective NLRP3 inhibitor, MCC950, as well as the specific caspase-1 inhibitors VX-765 and Ac-YVAD-CHO for therapeutic purposes. Airway resistance was measured and bronchoalveolar lavage fluid was analyzed. Lungs were examined by histology, immunohistochemistry, Western blotting, and flow cytometry. TDI exposure elevated the expression of NLRP3 and caspase-1 that was coupled with increased airway hyperresponsiveness (AHR), neutrophil-dominated cell infiltration, pronounced goblet cell metaplasia, extensive collagen deposition, and increased TH2/TH17 responses. Both VX-765 and Ac-YVAD-CHO effectively inhibited the activation of caspase-1 in TDI-asthmatic mice that was accompanied by dramatic attenuation of AHR, airway inflammation, and airway remodeling, in addition to a decreased TH2 response and lower levels of IL-18 and IL-1β. MCC950 blocked the activation of NLRP3 and downregulated protein expression of caspase-1, IL-1β, and IL-18 in TDI-exposed mice. Furthermore, MCC950 remarkably alleviated AHR, airway inflammation, airway remodeling, and significantly suppressed TH2/TH17 responses. These findings suggested that blockade of the NLRP3/caspase-1 axis effectively prevents the progression of TDI-induced asthma and could be used as therapeutic targets for asthmatics.

Purpose The purpose of this study was to investigate the reproducibility of fluid-phase measurements in PBS-treated sputum supernatant, processed using the two-step method, of healthy and stable COPD individuals. Methods Nine healthy subjects and 23 stable COPD patients provided sputum twice within 6 days. A two-step sputum processing method was used to obtain PBS-treated supernatant and sputum cells. Soluble protein markers and IgG and IgM autoantibody profiles in PBS supernatant were analyzed using customized microarrays. Repeatability of measurements was assessed by paired-sample testing and an intraclass correlation coefficient, then graphically reported by Bland-Altman plot. Results There was no significant difference between the repeated detection of 8/10 types of soluble protein markers, all 13 types of IgG autoantibodies, and 12/13 types of corresponding IgM autoantibodies in PBS supernatant. The repeatability of measurements in PBS supernatant was substantial to very good for interleukin 6 (IL6), IL8, IL13, IL10, IL33, vascular endothelial growth factor, soluble receptor for advanced glycation end-products, and tumor necrosis factor-α; for IgG autoantibodies against aggrecan, centromere protein B (CENP-B), collagen II, collagen IV, cytochrome C, elastin, heat shock protein 47 (HSP47), HSP70, and La/Sjogren syndrome type B antigen; for IgM autoantibodies against CENP-B, collagen I, collagen II, collagen IV, cytokeratin 18, and HSP70; and for sputum neutrophils, macrophages and eosinophils count. Bland-Altman plots suggested good consistency within repeated measurements. Stable COPD patients differed from healthy subjects in the proportion of neutrophils and eosinophils; relative fluorescence intensity of anti-cytochrome C IgG, anti-aggrecan IgM, and anti-cytochrome C IgM. There was a significant positive correlation for stable COPD patients between sputum anti-collagen II IgG and post-bronchodilator FEV1%. Conclusion We confirmed fluid-phase measurements in PBS-treated sputum supernatant by high-throughput techniques with good repeatability. We demonstrated the presence of IgG and IgM autoantibodies to multiple antigens in the airways of COPD patients.

We aimed to evaluate the alteration of diagnosis of individual expert and multidisciplinary discussion (MDD) team in the longitudinal diagnostic assessment of idiopathic interstitial pneumonia (IIP). The retrospective analysis included 56 patients diagnosed as IIP by The First Affiliated Hospital of Guangzhou Medical University with follow-up visits during Jan 1st to Aug 31st 2014. Each expert was provided information in a sequential manner and was asked to assign an individual diagnosis and an MDD diagnosis after group discussion. The level of agreement among individual experts and between different visits was calculated by kappa and the agreement between individual specialist and MDD team with different consensus levels was measured by weighted-kappa coefficients. Follow-up data changed the original clinical diagnosis and MDD diagnosis in 24.1% and 10.7% of all cases, respectively, and clinician and MDD consensus level in 55.4% and 25.0%, respectively. The diagnostic performance of individual clinicians or radiologist was closer to that of the MDD compared with the pathologist, and follow-up further increased the agreement. The longitudinal evaluation of patients with IIP improved the inter-observer agreement in a multidisciplinary team. The performance of individual clinicians or radiologist was approaching the accuracy of multidisciplinary team when provided with follow-up data.

Disruption of epithelial cell-cell junctions is essential for the initiation and perpetuation of airway inflammation in asthma. We’ve previously reported compromised epithelial barrier integrity in a toluene diisocyanate (TDI)-induced occupational asthma model. This study is aimed to explore the role of transient receptor potential vanilloid 4 (TRPV4) and transient receptor potential ankyrin 1 (TRPA1) in the dysfunction of adherens junctions in TDI-induced asthma. Mice were sensitized and challenged with TDI for a chemical-induced asthma model. Selective blockers of TRPV4 glycogen synthase kinase (GSK)2193874, 5 and 10 mg/kg) and TRPA1 (HC030031, 10 and 20 mg/kg) were intraperitoneally given to the mice. Immunohistochemistry revealed different expression pattern of TRPV4 and TRPA1 in lung. TDI exposure increased TRPV4 expression in the airway, which can be suppressed by GSK2193874, while treatment with neither TDI alone nor TDI together with HC030031 led to changes of TRPA1 expression in the lung. Blocking either TRPV4 or TRPA1 blunted TDI-induced airway hyperreactivity, airway neutrophilia and eosinophilia, as well as Th2 responses in a dose-dependent manner. At the same time, membrane levels of E-cadherin and β-catenin were significantly decreased after TDI inhalation, which were inhibited by GSK2193874 or HC030031. Moreover, GSK2193874 and HC030031 also suppressed serine phosphorylation of glycogen synthase kinase 3β, tyrosine phosphorylation of β-catenin, as well as activation and nuclear transport of β-catenin in mice sensitized and challenged with TDI. Our study suggested that both TRPV4 and TRPA1 contribute critically to E-cadherin and β-catenin dysfunction in TDI-induced asthma, proposing novel therapeutic targets for asthma.

Introduction: Noninvasive ventilation (NIV) has been used to alleviate hypoxemia and dyspnea, but there is no consensus on the application of NIV in patients with coronavirus disease 2019 (COVID-19). Some staff use NIV as the rescue therapy which might lead to the adverse outcomes. This study was to identify early factors associated with intubation to help the medical staff select appropriate patients for receiving NIV treatment.Methods: Patients with laboratory-confirmed COVID-19 who were treated with NIV in emergency department or ICU of the Third People's Hospital (the only designated hospital for treating COVID-19 in Shenzhen) between January 1 and August 31, 2020, were retrospectively analyzed.Results: Thirty-nine patients with COVID-19 treated with NIV were included; of them, 16 (41%) received endotracheal intubation and 3 (8%) died. Significant differences were observed between intubated and non-intubated patients in PaO2/FiO2 before NIV initiation, hospitalization duration, NIV as the rescue therapy, and PaO2/FiO2 of ≤200 mmHg after 1–2 h of NIV initiation. Notably, 1–2 h after NIV initiation, a PaO2/FiO2 of ≤200 mmHg (odds ratio [OR], 9.35; 95% confidence interval [CI], 1.84–47.62; P = 0.007) and NIV as the rescue therapy (OR, 5.43; 95% CI, 1.09–27.12; P = 0.039) were the risk factors for intubation.Conclusions: In patients with COVID-19-related acute hypoxemic respiratory failure receiving NIV, close attention should be paid to PaO2/FiO2 after 1–2 h of NIV initiation. Also, using NIV as rescue therapy should draw our awareness that it might delay escalation of respiratory support and lead to adverse outcomes.

As a vital pivot for the human circulatory system, the brain-gut axis is now being considered as an important channel for many of the small immune molecules’ transductions, including interleukins, interferons, neurotransmitters, peptides, and the chemokines penetrating the mesentery and blood brain barrier (BBB) during the development of an ischemic stroke (IS). Hypoxia-ischemia contributes to pituitary and neurofunctional disorders by interfering with the molecular signal release and communication then providing feedback to the gut. Suffering from such a disease on a long-term basis may cause the peripheral system’s homeostasis to become imbalanced, and it can also lead to multiple intestinal complications such as gut microbiota dysbiosis (GMD), inflammatory bowel disease (IBD), necrotizing enterocolitis (NEC), and even the tumorigenesis of colorectal carcinoma (CRC). Correspondingly, these complications will deteriorate the cerebral infarctions and, in patients suffering with IS, it can even ruin the brain’s immune system. This review summarized recent studies on abnormal immunological signal exchange mediated polarization subtype changes, in both macrophages and microglial cells as well as T-lymphocytes. How gut complications modulate the immune signal transduction from the brain are also elucidated and analyzed. The conclusions drawn in this review could provide guidance and novel strategies to benefit remedies for both IS and relative gut lesions from immune-prophylaxis and immunotherapy aspects.

BackgroundCough variant asthma (CVA) is a special phenotype of asthma. The precise inflammatory features of patients with CVA, however, is still unclear. We aimed to elucidate the differential inflammatory features in patients with CVA in contrast to patients with classic asthma (CA). MethodsA total of 68 patients with persistent uncontrolled asthma (34 with CVA, 34 with CA) in Shenzhen People’s Hospital between August 2018 and May 2019 were enrolled. We collected the demographic data, pulmonary function test (PFT) parameters, hematological variables, and several serum biomarkers. Receiver operating characteristic (ROC) curves were generated to evaluate the values of biomarkers for distinguishing between CVA and CA. ResultsCompared with CA group, CVA group had a higher percentage of females (73.5 vs. 50%, P = 0.046), lower proportion of asthma family history (5.9 vs. 29.4%, P = 0.011), shorter disease course [12.0 (4.8, 39) vs. 96.0 (48.0, 240.0) months, P < 0.001], and better pulmonary function (P all < 0.05). Increased levels of blood eosinophil count [0.35 (0.13, 0.94) vs. 0.34 (0.01, 0.53) X109/L, P = 0.045], eosinophil percentage [6.3 (3.0, 9.8) vs. 4.4 (0.2, 8.4) %, P = 0.046], serum IL-5 [104.19 (89.03, 199.66) vs. 84.57 (26.87, 103.58) ng/L, P = 0.011], and serum herpesvirus entry mediator (HVEM) [128.53 (100.89, 204.83) vs. 90.71 (37.05, 108.08) pg/mL, P = 0.002] were also found in CVA patients compared to those in CA patients. The logistic analysis revealed that serum HVEM had a strong predictive power for CVA group (OR = 1.105, P = 0.015). The sensitivities and specificity of serum HVEM and IL-5 to distinguish between CVA and CA at optimal cut-offs were 85.0% and 61.1%; 85.0% and 61.1%, respectively. AUCs of serum HVEM and IL-5 were 0.789 and 0.739, respectively. Furthermore, serum HVEM and IL-5 had no correlation with PFT parameters in CVA group (P all > 0.05).ConclusionsElevated serum levels of HVEM and IL-5 are exhibited in CVA patients, which may indicate their important roles in the pathogenesis and progression of CVA.

Background Primary ciliary dyskinesia (PCD) is an autosomal recessive disorder. The genetic factors contributing to PCD pathogenesis remain elusive for approximately 20–35% of patients with complex and abnormal clinical phenotypes. Our study aimed to identify causative variants of sporadic PCD genes using whole-exome sequencing (WES). Result All patients were diagnosed with PCD based on clinical phenotype or transmission electron microscopy (TEM) images of cilia. WES and bioinformatic analysis were then conducted for patients with PCD. Identified candidate variants were validated by Sanger sequencing. Pathogenicity of candidate variants was then evaluated using in silico software and the American College of Medical Genetics and Genomics (ACMG) database. In total, 15 rare variants were identified in five patients with PCD. Five new variants of CCDC40, DNAH1, DNAAF3, and DNAI1 were considered causative variants and included one splicing and three homozygous variants. Conclusion Our study demonstrated that patients with PCD carry rare causative variants of multiple genes. Our findings indicated that not only known causative genes but also other functional genes should be considered for heterogeneous genetic disorders.

Little is known about airway mycobiome, and its relationship with bacterial microbiome in chronic obstructive pulmonary disease (COPD). Here we report the first simultaneous characterization of sputum bacterial and fungal microbiome in 84 stable COPD and 29 healthy subjects, using 16S ribosomal DNA and fungal internal transcribed spacer DNA sequencing. Ascomycota predominated over Basidiomycota in fungal microbiome both in COPD patients and healthy controls. Meyerozyma, Candida, Aspergillus and Schizophyllum were most abundant at the genus level. There was a significant inverse correlation between bacterial and fungal microbial diversity, both of which altered in opposite directions in COPD patients versus controls, and in frequent versus non-frequent exacerbators. An enhanced bacterial-fungal ecological interaction was observed in COPD patients, which was characterized by higher proportion of co-occurrence intrakingdom interactions and co-exclusive interkingdom interactions. In COPD, four mutually co-occurring fungal operational taxonomic units (OTUs) in Candida palmioleophila, Aspergillus and Sordariomycetes exhibited co-exclusive relationships with other fungal OTUs, which was specifically present in frequent exacerbators but not in non-frequent exacerbators. The perturbed bacterial-fungal interactions in COPD were associated with increased airway inflammatory mediators such as IL-6 and IL-8. The disruption of airway bacterial-fungal community balance, characterized by the loss of commensal bacterial taxa and enriched pathogenic fungal taxa, is implicated in COPD. The emergence of pathogenic fungi such as Candida and Aspergillus could be a marker for the frequent exacerbator phenotype. The airway mycobiome is an important cofactor mediating pathogenic infection and host inflammation in COPD.

Ciprofloxacin and extended-spectrum cephalosporins are the choice for treatment of severe nontyphoidal S. enterica infections in adults. S. enterica serotype Kentucky ST198 has gained epidemiological importance globally, because the clone is frequently resistant to both of these high-level-resistance drug groups. The genetic and epidemiological characterization of S. Kentucky has been well studied in Western countries; however, the information is unclear for China., Salmonella enterica serotype Kentucky is frequently associated with high-level fluoroquinolone resistance and has gained epidemiological importance globally. A retrospective screening was performed to understand the national prevalence of ciprofloxacin-resistant S. Kentucky in China. S. enterica strains (n = 15,405) were collected within the frame of two national surveillance networks between 2013 and 2017. Thirty-three S. Kentucky strains were detected in 5 of 10 provinces, and 27 were assigned to sequence type 198 (ST198). The 27 isolates were multidrug resistant, with high-level resistance to ciprofloxacin, and 21 isolates were further resistant to extended-spectrum cephalosporins (ESCs). Phylogenomic analysis classified ST198 isolates into two clades (198.1 and 198.2), and recent occurrences of inter-/intraregion and interhost transmission were identified. Phylogenetic reconstruction with a global collection showed that one subclade of clade 198.2 was clustered with historical strains from Egypt, and the other one was clustered with strains from Southeast Asia. Isolates of clade 198.1 were clustered with strains isolated from North America. The various patterns of mutations detected in quinolone resistance-determining regions of GyrA and ParC are accordant with the phylogenetic structure. These findings indicate that our isolates may have various origins. SGI1 was exclusively detected in isolates of clade 198.2 with a highly mosaic structure, which were mainly identified as SGI1-K derivatives. Plasmid-mediated quinolone resistance genes qnrS1 and aac(6′)-Ib-cr were identified in three isolates, and blaCTX-M-9 and blaCTX-M-27 were detected in 20 of 21 ESC-resistant isolates. This is the first report of the genetic and epidemiological characterization for the S. Kentucky epidemic clone ST198 in China, warranting the necessity of surveillance for the high-risk clone. IMPORTANCE Ciprofloxacin and extended-spectrum cephalosporins are the choice for treatment of severe nontyphoidal S. enterica infections in adults. S. enterica serotype Kentucky ST198 has gained epidemiological importance globally, because the clone is frequently resistant to both of these high-level-resistance drug groups. The genetic and epidemiological characterization of S. Kentucky has been well studied in Western countries; however, the information is unclear for China. To fill in the gap, we here did a retrospective screening on a large collection in China, and ST198 isolates were systematically analyzed by whole-genome sequencing. Our study revealed that multidrug-resistant ST198 has spread in five provinces, and the occurrences of interregion and cross-host clonal disseminations were detected. Of note, phylogenomic analysis suggests that the Chinese isolates may have emerged with diverse origins, including Egypt, Southeast Asia, and North America. This study warrants the necessity of surveillance for the high-risk clone to prevent its further dissemination in China.

Background： Primary ciliary dyskinesia (PCD) is an autosomal recessive disorder. The genetic factors contributing to PCD pathogenesis remain elusive for approximately 20–35% of patients with complex and abnormal clinical phenotypes. Our study aimed to identify causative variants of sporadic PCD genes using whole-exome sequencing (WES). Result：All patients were diagnosed with PCD based on clinical phenotype or transmission electron microscopy (TEM) images of cilia. WES and bioinformatic analysis were then conducted for patients with PCD. Identified candidate variants were validated by Sanger sequencing. Pathogenicity of candidate variants was then evaluated using in silico software and the American College of Medical Genetics and Genomics (ACMG) database. In total, 15 rare variants were identified in five patients with PCD. Five new variants of CCDC40, DNAH1, DNAAF3, and DNAI1 were considered causative variants and included one splicing and three homozygous variants. Conclusion： Our study demonstrated that patients with PCD carry rare causative variants of multiple genes. Our findings indicated that not only known causative genes but also other functional genes should be considered for heterogeneous genetic disorders.

Background Differences between adult patients with severe early-onset and late-onset asthma have not been well studied. Objectives To determine the phenotypic distinction regarding age at onset in patients with severe asthma. Methods The present study enrolled thirty-two patients with severe early-onset (onset age 12 years) asthma. Severe asthma was defined according to Global Initiative for Asthma criteria. The clinical, spirometric, and laboratory parameters were collected for group comparisons. Results Among the 64 patients included (mean age, 46.22 ± 13.90 years; 53.1% male), the mean percent of predicted forced expiratory volume in 1 s (FEV1) was 68.43 ± 20.55%. Patients with severe early-onset asthma had a younger age, longer duration of asthma, higher rate of family history, and better small-airway function (MEF25% and MMEF75/25%) compared with severe late-onset asthma. Furthermore, levels of serum IL-17 and sputum neutrophil percentage were significantly higher for patients with severe early-onset asthma (P = 0.016, 0.033, respectively). Multiple logistic regression analysis revealed that increased serum IL-17 (odds ratio = 1.065, P = 0.016) was independently associated with severe early-onset asthma. The combination of serum IL-17 and sputum neutrophil percentage yielded a sensitivity of 80.0% and a specificity of 86.7% for identifying patients with severe early-onset asthma. Conclusions Patients with severe early-onset asthma exhibit elevated levels of serum IL-17 and sputum neutrophil percentage, suggesting a potential role in the pathogenesis of severe early-onset phenotype.

Jie Li, Chen Qiu, Peng Xu, Yongzhen Lu, Rongchang Chen Key Laboratory of Shenzhen Respiratory Disease, Shenzhen Institute of Respiratory Disease, Shenzhen People’s Hospital (The First Affiliated Hospital of Southern University of Science and Technology, The Second Clinical Medical College of Jinan University), Shenzhen, Guangdong, People’s Republic of ChinaCorrespondence: Jie Li; Rongchang ChenKey Laboratory of Shenzhen Respiratory Disease, Shenzhen Institute of Respiratory Disease, Shenzhen People’s Hospital (The First Affiliated Hospital of Southern University of Science and Technology, The Second Clinical Medical College of Jinan University), Shenzhen, Guangdong, People’s Republic of ChinaEmail ljszry2018@126.com; chenrc@vip.163.comObjective: The present study was conducted to elucidate the protective effect of Casticin against chronic obstructive pulmonary disease (COPD) in rats.Methods: The COPD in rats was induced by the controlled cigarette smoke, and CST (10, 20, and 30 mg/kg) was injected into the cigarette-smoke exposed rats. Blood was taken from the abdominal vein and centrifuged (1500×g, 4°C, 15min); plasma was collected and used for the determination of various biochemical parameters.Results: The results of the study suggested that CST significantly improved the lung functions of the rats in a dose-dependent manner. It also causes a reduction of white blood cells, neutrophils, and macrophages in BALF of rats. The plasma level of leptin and C-reactive protein together with pro-inflammatory cytokines (TNF-α, IL-1β, and IL-6) were also significantly restored to near to normal in CST-treated group. In Western blot analysis, CST causes significant inhibition of the NF-ĸB and iNOS pathway.Conclusion: Our study demonstrated that the CST protects lungs against COPD via improving lung functions and inhibition of oxidative stress and inflammation.Keywords: COPD, Casticin, smoke, inflammation, oxidative stress, NF-ĸB

BackgroundLittle is known about airway mycobiome, and its relationship with bacterial microbiome in chronic obstructive pulmonary disease (COPD).MethodsHere we report the first simultaneous characterization of sputum bacterial and fungal microbiome in 84 stable COPD and 29 healthy subjects, using 16S ribosomal DNA and fungal internal transcribed spacer DNA sequencing.ResultsAscomycota predominated over Basidiomycota in fungal microbiome both in COPD patients and healthy controls. Meyerozyma, Candida, Aspergillus and Schizophyllum were most abundant at the genus level. There was a significant inverse correlation between bacterial and fungal microbial diversity, both of which altered in opposite directions in COPD patients versus controls, and in frequent versus non-frequent exacerbators. An enhanced bacterial-fungal ecological interaction was observed in COPD patients, which was characterized by higher proportion of co-occurrence intrakingdom interactions and co-exclusive interkingdom interactions. In COPD, four mutually co-occurring fungal operational taxonomic units (OTUs) in Candida palmioleophila, Aspergillus and Sordariomycetes exhibited co-exclusive relationships with other fungal OTUs, which was specifically present in frequent exacerbators but not in non-frequent exacerbators. Conversely, the mutual co-occurrence interactions between bacterial OTUs in Rothia mucilaginosa, Streptococcus, Veillonella and Prevotella, showed up in non-frequent exacerbators but not in frequent exacerbators. The perturbed bacterial-fungal interactions in COPD were associated with increased airway inflammatory mediators such as IL-6 and IL-8.InterpretationThe disruption of airway bacterial-fungal community balance, characterized by the loss of commensal bacterial taxa and enriched pathogenic fungal taxa, is implicated in COPD. The airway mycobiome is an important cofactor mediating COPD pathogenic infection and host inflammation.Clinical Trial Registrationwww.clinicaltrials.gov (NCT 03240315).

Coronavirus disease (COVID-19) is an emerging viral infection that is rapidly spreading across the globe. SARS-CoV-2 belongs to the same coronavirus class that caused respiratory illnesses such as severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS). During the SARS and MERS outbreaks, many frontline healthcare workers were infected when performing high-risk aerosol-generating medical procedures as well as when providing basic patient care. Similarly, COVID-19 disease has been reported to infect healthcare workers at a rate of ~ 3% of cases treated in the USA. In this review, we conducted an extensive literature search to develop practical strategies that can be implemented when providing respiratory treatments to COVID-19 patients, with the aim to help prevent nosocomial transmission to the frontline workers.

Hypoxia promotes inflammation in the tumor microenvironment. Although hypoxia-inducible factor 1α (HIF1α) is a master modulator of the response to hypoxia, the exact mechanisms through which HIF1α regulates the induction of inflammation remain largely unclear. Using The Cancer Genome Atlas Lung Squamous Cell Carcinoma (TCGA-LUSC) database, we divided patients with LUSC into two groups based on low or high HIF1α expression. After analyzing the differentially expressed genes in these two groups, we found that HIF1α was positively correlated with interleukin 1A (IL1A) and IL6 expression. Our in vitro study showed that hypoxic stress did not induce IL1A or IL6 expression in tumor cells or macrophages but dramatically enhanced their expression when co-cultured with tumor cells. We then investigated the effect of tumor-derived exosomes on macrophages. Our data suggested that the changes in miR101 in the tumor-derived exosomes played an important role in IL1A and IL6 expression in macrophages, although the hypoxic stress did not change the total amount of exosome secretion. The expression of miR101 in exosomes was suppressed by hypoxic stress, since depletion of HIF1α in tumor cells recovered the miR101 expression in both tumor cells and exosomes. In vitro, miRNA101 overexpression or uptake enriched exosomes by macrophages suppressed their reprogramming into a pro-inflammatory state by targeting CDK8. Injection of miR101 into xenografted tumors resulted in the suppression of tumor growth and macrophage tumor infiltration in vivo. Collectively, this study suggests that the HIF1α-dependent suppression of exosome miR101 from hypoxic tumor cells activates macrophages to induce inflammation in the tumor microenvironment.

Background Diabetic cardiomyopathy (DCM) is a serious complication of diabetes that can lead to significant mortality. Cyclocarya paliurus is a tree, the leaves of which are often utilized to prevent and treat diabetes mellitus. Whether C. paliurus leaves can prevent or treat DCM, however, it remains to be formally assessed. The present study was therefore designed to assess the ability of C. paliurus to protect against DCM in db/db mice. Methods Male wild-type (WT) and db/db mice were administered C. paliurus ethanol leaf extracts (ECL) or appropriate vehicle controls daily via gavage, and levels of blood glucose in treated animals were assessed on a weekly basis. After a 10-week treatment, the levels of cardiac troponin I (cTn-I), lactate dehydrogenase (LDH), creatine kinase MB (CK-MB), aspartate transaminase (AST), total triglycerides (TG), and total cholesterol (TC) in serum were measured. Activities of malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase (CAT) and the levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and IL-6 in heart tissues were detected. Hematoxylin-eosin (HE) and Masson staining were conducted. The protein expression that related with oxidative stress and inflammatory reaction was evaluated by Western blotting. Results Compared with WT mice, the TG, TC, and blood glucose levels in db/db mice increased significantly, which were reduced by ECL treatment. Compared with WT mice, the levels of LDH, CK-MB, AST, and cTn-I in serum and MDA in heart tissues of db/db mice increased significantly. Activities of SOD, GSH-Px, and CAT in heart tissues of db/db mice decreased significantly. The levels of inflammatory cytokines (TNF-α, IL-1β, and IL-6) in heart tissues of db/db mice increased remarkably. However, ECL treatment improved the above pathological changes significantly. ECL alleviated pathological injury and fibrosis in heart tissues of mice. Western blotting showed that ECL increased Bcl-2 level and decreased Bax, cle-caspase-3, and cle-caspase-9 expression. Furthermore, ECL inhibited NF-κB nuclear translocation and increased PI3K and p-Akt expressions. Conclusion Our results indicate that ECL treatment can markedly reduce pathological cardiac damage in db/db mice through antiapoptotic, antifibrotic, and anti-inflammatory mechanisms. Specifically, this extract was able to suppress NF-κB activation via the PI3K/Akt signaling pathway. Given its diverse activities and lack of significant side effects, ECL may thus have therapeutic value for the treatment of DCM.

Background Reported data on the disease spectrum of interstitial lung diseases (ILDs) of China are sparse and varied. We aimed to investigate the spectrum of ILDs and the distribution of diagnostic methods under a uniform diagnosis. Methods This retrospective study enrolled ILDs cases from Guangzhou Institute of Respiratory Health (GIRH). All cases were classified into specific subgroups of ILDs according to updated guidelines. Results A total of 1,945 subjects were enrolled from January 2012 to December 2017. The mean age was 57.9 years, and 1,080 (55.5%) patients were male. The most common subtype of ILDs was idiopathic pulmonary fibrosis (IPF, 20.3%), followed by interstitial pneumonia with autoimmune features (IPAF, 17.9%), connective tissue disease associated ILD (CTD-ILD, 18.3%) and unclassifiable idiopathic interstitial pneumonia (UIIP, 14.7%). A total of 818 (42.1%) patients underwent lung biopsy in order to obtain a histological diagnose. TBLB was performed in 565 (29.0%) patients, eleven of whom underwent SLB because TBLB failed to obtain lung samples. SLB was performed in 213 (11.0%) patients and TBCB was performed in 51 (2.6%) patients. Among them, histological results were considered clinically helpful in 722 (88.3%) cases, and provided definitive histopathological diagnoses in 368 cases. Surgical lung biopsy (SLB) was performed in 213 (10.9%) subjects, while 115 (54.0%) cases were performed among the idiopathic interstitial pneumonia (IIP). Among SLB cases in IIP, the highest rate of SLB was desquamative interstitial pneumonia/respiratory bronchiolitis-interstitial lung disease (DIP/RB-ILD, 10/10), lymphoid interstitial pneumonia (LIP, 9/9), followed by cryptogenic organizing (COP, 18/26), nonspecific interstitial pneumonia (NSIP, 22/53), IPF (43/395), UIIP (13/285). Conclusions IPF was the most common ILDs in our ILD center, followed by IPAF, CTD-ILD and UIIP. Histological information may help to establish diagnostic algorithm in ILD.

Summary COVID-19, caused by SARS-CoV-2, is a virulent pneumonia, with >4,000,000 confirmed cases worldwide and >290,000 deaths as of May 15, 2020. It is critical that vaccines and therapeutics be developed very rapidly. Mice, the ideal animal for assessing such interventions, are resistant to SARS-CoV-2. Here, we overcome this difficulty by exogenous delivery of human ACE2 with a replication-deficient adenovirus (Ad5-hACE2). Ad5-hACE2-sensitized mice developed pneumonia characterized by weight loss, severe pulmonary pathology, and high-titer virus replication in lungs. Type I interferon, T cells and, most importantly, signal transducer and activator of transcription 1 (STAT1) are critical for virus clearance and disease resolution in these mice. Ad5-hACE2-transduced mice enabled rapid assessments of a vaccine candidate, of human convalescent plasma, and of two antiviral therapies (poly I:C and remdesivir). In summary, we describe a murine model of broad and immediate utility to investigate COVID-19 pathogenesis, and to evaluate new therapies and vaccines., An adenoviral transduction-based mouse model that can be infected with SARS-CoV-2 provides a tool to understand host factors involved in viral infection and clearance as well as potential therapeutic modalities.

Middle East respiratory syndrome coronavirus (MERS-CoV) causes severe acute respiratory disease in humans. MERS-CoV strains from early epidemic clade A and contemporary epidemic clade B have not been phenotypically characterized to compare their abilities to infect cells and mice. We isolated the clade B MERS-CoV ChinaGD01 strain from a patient infected during the South Korean MERS outbreak in 2015 and compared the phylogenetics and pathogenicity of MERS-CoV EMC/2012 (clade A) and ChinaGD01 (clade B) in vitro and in vivo Genome alignment analysis showed that most clade-specific mutations occurred in the orf1ab gene, including mutations that were predicted to be potential glycosylation sites. Minor differences in viral growth but no significant differences in plaque size or sensitivity to beta interferon (IFN-β) were detected between these two viruses in vitro ChinaGD01 virus infection induced more weight loss and inflammatory cytokine production in human DPP4-transduced mice. Viral titers were higher in the lungs of ChinaGD01-infected mice than with EMC/2012 infection. Decreased virus-specific CD4+ and CD8+ T cell numbers were detected in the lungs of ChinaGD01-infected mice. In conclusion, MERS-CoV evolution induced changes to reshape its pathogenicity and virulence in vitro and in vivo and to evade adaptive immune response to hinder viral clearance.IMPORTANCE MERS-CoV is an important emerging pathogen and causes severe respiratory infection in humans. MERS-CoV strains from early epidemic clade A and contemporary epidemic clade B have not been phenotypically characterized to compare their abilities to infect cells and mice. In this study, we showed that a clade B virus ChinaGD01 strain caused more severe disease in mice, with delayed viral clearance, increased inflammatory cytokines, and decreased antiviral T cell responses, than the early clade A virus EMC/2012. Given the differences in pathogenicity of different clades of MERS-CoV, periodic assessment of currently circulating MERS-CoV is needed to monitor potential severity of zoonotic disease.

Objective Spirometric lung function is usually used to evaluate respiratory health. However, the impact of lung function on extra-pulmonary diseases and all-cause mortality has not been fully elucidated, especially in people without chronic obstructive pulmonary disease (COPD). Patients and Methods Participants aged ≥20 and underwent spirometry test from the US National Health and Nutrition Examination Surveys (NHANES) 2007–2012 were analyzed in this study. Multivariate logistic and Cox regressions were used to evaluate the impact of forced expiratory volume in 1 second percent of predicted (FEV1% predicted) and forced vital capacity percent of predicted (FVC% predicted) on 14 extra-pulmonary diseases and all-cause morbidity after adjusting for multiple confounders. Results During 2007–2012, 1800 COPD patients and 11,437 non-COPD subjects were included. The prevalence of hypertension, diabetes mellitus (DM), dyslipidemia, metabolic syndrome (MS), congestive heart failure (CHF), coronary disease, stroke, chronic kidney disease (CKD), arthritis, cancer, underweight and osteoporosis in COPD patients was higher than that in the non-COPD population. After adjusting for confounders, the decrease of FEV1% predicted and FVC% predicted was related with higher odds of having hypertension, DM, obesity, MS, CHF, coronary disease and depression (OR > 1, P

Objective This study was designed to investigate the protective effects of didymin (Did) on doxorubicin (DOX)-induced cardiotoxicity. Methods After pretreatment with Did (2, 4, 8 mg/kg intraperitoneal i.p.) for 7 d, the male C57 mice were injected with single dose of DOX (20 mg/kg i.p.). The cardioprotective effect of Did was observed on the 7th day after DOX treatment. Results DOX delayed body growth and caused cardiac tissue injury, oxidative stress, and mitochondrial dysfunction. Similar experiments in H9C2 cardiomyocytes showed that DOX reduced cell viability, increased generation of reactive oxygen species (ROS) and fragmentation of DNA, decreased mitochondrial membrane potential, and induced cardiomyocyte apoptosis. However, all of these adverse effects were suppressed by Did pretreatment. Did increased protein expression of glutamate-L-cysteine ligase catalytic subunit (GCL), heme oxygenase 1 (HO-1), and nuclear factor erythroid 2-related factor 2 (Nrf2). Besides, Did also induced activation of PI3K/AKT. Conclusion These findings indicated Did prevented DOX-induced cardiac injury and apoptosis via activating PI3K/AKT/Nrf2 signaling pathway.

Background Autoimmunity plays a role in the pathogenesis of chronic obstructive pulmonary disease (COPD). However, the autoantibody responses and their clinical correlation patterns in COPD patients with and without airway eosinophilic inflammation are unknown. The aim of this study was to compare the autoantibody profiles and their clinical associations in stable COPD patients, stratified by airway inflammatory phenotypes. Methods Matched sputum and serum, obtained from 62 stable COPD patients and 14 age-matched controls, were assayed for the presence of IgG and IgM antibodies against 13 autoantigens using protein array. A sputum eosinophil count ≥3% was used as cut-off value to stratify COPD patients into eosinophilic and non-eosinophilic groups. Correlation network analysis was used to evaluate the correlation patterns among autoantibody and clinical variables in each group. Results There were no significant differences of clinical parameters and autoantibody levels between the two COPD groups. In non-eosinophilic COPD, sputum anti-CytochromeC_IgG and anti-Aggrecan_IgM were significantly higher than those in healthy controls, and prior exacerbation was positively associated with lung function and sputum anti-Collagen-IV_IgG. While in eosinophilic COPD, sputum/serum anti-heat shock protein (HSP)47_IgG, serum anti-HSP70_IgG and serum anti-Amyloid-beta_IgG were significantly lower than those in healthy controls, and no significant correlation between prior exacerbations and lung function was found. Differences were also observed in network hubs, with the network for non-eosinophilic COPD possessing 9 hubs comprising two lung function parameters and seven autoantibodies, compared with eosinophilic COPD possessing 12 hubs all comprising autoantibodies. Conclusions Autoantibody responses were heterogeneous and differentially correlated with the exacerbation risk and other clinical parameters in COPD patients of different inflammatory phenotypes. These findings provide useful insight into the need for personalized management for preventing COPD exacerbations.

Identification of risk factors for antibiotic treatment failure is urgently needed in acute exacerbations of chronic obstructive pulmonary disease (AECOPD). Here we investigated the relationship between sputum microbiome and clinical outcome of choice of initial antibiotics during hospitalization of AECOPD patients. Sputum samples of 41 AECOPD patients and 26 healthy controls were collected from Guangzhou Medical University, China. Samples were processed for 16S rRNA gene-based microbiome profiling. Thirty patients recovered with initial antibiotic treatment (antibiotic success or AS), while 11 patients showed poor outcome (antibiotic failure or AF). Substantial differences in microbiome were observed in AF versus AS patients and healthy controls. There was significantly decreased alpha diversity and increased relative abundances of Pseudomonas, Achromobacter, Stenotrophomonas and Ralstonia in AF patients. Conversely, Prevotella, Peptostreptococcus, Leptotrichia and Selenomonas were depleted. The prevalence of Selenomonas was markedly reduced in AF versus AS patients (9.1 % versus 60.0 %, P = 0.004). The AF patients with similar microbiome profiles in general responded well to the same new antibiotics in the adjusted therapy, indicating sputum microbiome may help guide the adjustment of antibiotics. Random forest analysis identified five microbiome operational taxonomic units together with C-reactive protein, procalcitonin and blood neutrophil count showing best predictability for antibiotic treatment outcome (area under curve 0.885). Functional inference revealed an enrichment of microbial genes in xenobiotic metabolism and antimicrobial resistance in AF patients, whereas genes in DNA repair and amino acid metabolism were depleted. Sputum microbiome may determine the clinical outcome of initial antibiotic treatment and be considered in the risk management of antibiotics in AECOPD.

Middle East respiratory syndrome coronavirus (MERS-CoV) causes severe acute respiratory disease in humans. MERS-CoV strains from early epidemic clade A and contemporary epidemic clade B have not been phenotypically characterized to compare their abilities to infect cells and mice. We isolated the clade B MERS-CoV ChinaGD01 strain from a patient infected during the South Korean MERS outbreak in 2015 and compared the phylogenetics and pathogenicity of MERS-CoV EMC/2012 (clade A) and ChinaGD01 (clade B) in vitro and in vivo. Genome alignment analysis showed that most clade-specific mutations occurred in the orf1ab gene, including mutations that were predicted to be potential glycosylation sites. Minor differences in viral growth but no significant differences in plaque size or sensitivity to beta interferon (IFN-β) were detected between these two viruses in vitro. ChinaGD01 virus infection induced more weight loss and inflammatory cytokine production in human DPP4-transduced mice. Viral titers were higher in the lungs of ChinaGD01-infected mice than with EMC/2012 infection. Decreased virus-specific CD4(+) and CD8(+) T cell numbers were detected in the lungs of ChinaGD01-infected mice. In conclusion, MERS-CoV evolution induced changes to reshape its pathogenicity and virulence in vitro and in vivo and to evade adaptive immune response to hinder viral clearance. IMPORTANCE MERS-CoV is an important emerging pathogen and causes severe respiratory infection in humans. MERS-CoV strains from early epidemic clade A and contemporary epidemic clade B have not been phenotypically characterized to compare their abilities to infect cells and mice. In this study, we showed that a clade B virus ChinaGD01 strain caused more severe disease in mice, with delayed viral clearance, increased inflammatory cytokines, and decreased antiviral T cell responses, than the early clade A virus EMC/2012. Given the differences in pathogenicity of different clades of MERS-CoV, periodic assessment of currently circulating MERS-CoV is needed to monitor potential severity of zoonotic disease.

Background: The severe acute respiratory syndrome coronavirus-2 outbreak was identified in China in December 2019 and spread worldwide, reaching the pandemic levels. However, a specific, effective and proven therapy for the patients with coronavirus disease 2019 (COVID-19) remains elusive. We aim to compare the efficacy and the safety of three antiviral monotherapies (chloroquine phosphate, arbidol (Umifenovir) or lopinavir/ritonavir) in non-severe, hospitalised COVID-19 patients.Methods: We retrospectively analysed the hospitalised, laboratory-confirmed COVID-19 patients, treated with antiviral monotherapies at Huizhou Municipal Central Hospital between Jan 19 and Mar 16, 2020. Demographic and clinical data were extracted from electronic medical records. The primary outcome of the study was the viral shedding interval.Results: Twenty-seven patients with COVID-19 were included in the study with 10 receiving chloroquine phosphate, 11 receiving arbidol and 6 receiving lopinavir/ritonavir. Baseline demographics and clinical data were similar between groups. The median viral shedding interval in the lopinavir/ritonavir group was 13.0 days (95% CI: 12.2-23.8), while significantly shorter in the chloroquine group at 5.0 days (95% CI: 0.4-9.6) (p=0.003). A reduced median interval was also observed in the arbidol group, with 8.0 days (95%CI: 4.9-11.1) (p=0.008). Moreover, the hospitalisation duration was shorter in the chloroquine (9.3 ± 1.8 days, pConclusions: Chloroquine and arbidol could not only shorten the viral shedding interval but also decreased the hospitalisation duration and hospitalisation expenses.Trial registration: The ethics committee of the Huizhou Municipal Central Hospital approved this study, and the trial was registered with www.chictr.org.cn (ChiCTR2000030931).

To investigate the effect and tolerance of non-invasive ventilation (NIV) with helmet in patients with respiratory failure caused by acute exacerbation of chronic obstructive pulmonary disease (AECOPD) and the effect on improving blood gas, alleviating dyspnea and the occurrence of complications.Patients with AECOPD and respiratory failure admitted to emergency intensive care unit (EICU) and respiratory intensive care unit (RICU) of the First Affiliated Hospital of Zhengzhou University from January 1st, 2018 to May 31st, 2019 were enrolled. After obtaining the informed consent of the patients or their authorized family members, the patients were divided into two groups: the helmet group and the facial mask group by random number table. NIV was carried out by using helmet or facial mask, respectively. During the course of NIV (immediately, 1 hour, 4 hours and at the end of NIV), the tolerance score, blood gas analysis, heart rate (HR), respiratory rate (RR) of patients were monitored, and the incidence of tracheal intubation, in-hospital mortality and complications were observed. Kaplan-Meier survival curve was plotted to analyze the 30-day cumulative survival of the two groups.A total of 82 patients with AECOPD and respiratory failure were included during the study period. After excluding patients with the oxygenation index (PaONIV with helmet has better comfort for patients with AECOPD combined with respiratory failure, and better effect on improving oxygenation and relieving dyspnea, and its effect on carbon dioxide emissions is not inferior to that of traditional mask NIV.

Background Patients with cervical spinal cord injuries (CSCIs) may be required to undergo tracheostomy. However, in patients undergoing anterior cervical fusion (ACF), percutaneous dilational tracheostomy (PDT) may be delayed given the risk of cross-contamination. We aimed to evaluate the risk of surgical site infection (SSI) in early PDT in patients with traumatic CSCI after ACF. Methods All trauma patients admitted to the intensive care unit from 2008 to 2018 were retrospectively analyzed. Patients with CSCIs who underwent both ACF and PDT were identified, with or without posterior cervical fusion. Cases were classified as having undergone early PDT (≤4 days after ACF) versus late PDT (>4 days after ACF). Propensity scores were matched, and outcomes were compared between matched groups to reduce confounding by indication. Results From a total of 133 enrolled patients, a well-balanced propensity-matched cohort of 68 patients was defined. On the basis of the comparison of outcomes after matching, no significant difference in SSI was observed between both groups. There was no patient with SSI in the early PDT group (0%), whereas there were 2 SSI patients (5.9%) in the late PDT group (P = 0.493): The tracheostomy site was involved in 1, and the posterior approach site was involved in the other. Early PDT was associated with a shorter duration of mechanical ventilation (P = 0.042). There were no significant differences in the length of intensive care unit stay and hospital mortality between groups. Conclusions Early PDT within 4 days after ACF did not increase the risk of SSI compared with late PDT in patients with traumatic CSCIs.

Mingshan Xue,1,* Chuanxu Cai,2,* Lili Guan,1,* Yifan Xu,1 Jinsheng Lin,1 Yifeng Zeng,1 Haisheng Hu,1 Rongchang Chen,1 Hongman Wang,3 Luqian Zhou,1 Baoqing Sun1 1Guangzhou Institute of Respiratory Health, State Key Laboratory of Respiratory Disease, National Clinical Research Center of Respiratory Disease, First Affiliated Hospital of Guangzhou Medical University, Guangzhou, People’s Republic of China; 2Department of Laboratory Medicine, Shenzhen Institute of Respiratory Diseases, Shenzhen People’s Hospital, First Affiliated Hospital of Southern University of Science and Technology, Second Clinical Medical College of Jinan University, Shenzhen, People’s Republic of China; 3Department of Respiratory and Critical Care Medicine, The Fifth Affiliated Hospital of Zunyi Medical University Zhuhai, Zhuhai, People’s Republic of China*These authors contributed equally to this workCorrespondence: Luqian Zhou; Baoqing Sun Email zhlx09@163.com; sunbaoqing@vip.163.comBackground and Objective: Severe chronic obstructive pulmonary disease (COPD) is the terminal stage of the disease characterized by declined lung function, malnutrition, and poor prognosis. Such patients cannot tolerate long-time sports rehabilitation owing to dyspnea and fail to achieve the desired therapeutic effect; therefore, increasing nutritional support will be an important strategy for them. The present study applied metabolomics technology to evaluate the correlation between serum concentrations of polyunsaturated fatty acid (PUFA) metabolites, nutritional status, and lung function in patients with COPD to provide a theoretical basis for accurate nutritional support.Materials and Methods: We enrolled 82 patients with stable severe COPD in our hospital. The general characteristics including height, weight, and lung function were recorded. Metabolomics was used to detect the concentrations of serum metabolites of n-3 and n-6 at baseline and at 24 and 52 weeks after enrollment. The correlations between nutrition level and pulmonary function and clinical indicators were evaluated.Results: The concentrations of n-3 and n-6 increased over time along with the progression of COPD. Body mass index (BMI) and percent of ideal body weight (IBW%) decreased with disease development, and BMI was found to be significantly correlated with FEV1% predicted and FEV1/FVC. Serum levels of n-6 metabolites such as linoleic acid (LA), γ-linoleic acid (GLA), and arachidonic acid (ARA) (all P < 0.01) and the n-3 metabolites such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) (all P < 0.05) showed significant correlations with BMI and were closely correlated with FEV1% predicted and FEV1/FVC of lung function (all P< 0.05).Conclusion: This study demonstrates that malnutrition in patients with severe COPD is progressive and is positively correlated with n-3 and n-6 polyunsaturated fatty acids and lung function.Keywords: chronic obstructive pulmonary disease, metabolomics, nutritional level

The aim is to diagnose COVID-19 earlier and to improve its treatment by applying medical technology, the “COVID-19 Intelligent Diagnosis and Treatment Assistant Program (nCapp)” based on the Internet of Things. Terminal eight functions can be implemented in real-time online communication with the “cloud” through the page selection key. According to existing data, questionnaires, and check results, the diagnosis is automatically generated as confirmed, suspected, or suspicious of 2019 novel coronavirus (2019-nCoV) infection. It classifies patients into mild, moderate, severe or critical pneumonia. nCapp can also establish an online COVID-19 real-time update database, and it updates the model of diagnosis in real time based on the latest real-world case data to improve diagnostic accuracy. Additionally, nCapp can guide treatment. Front-line physicians, experts, and managers are linked to perform consultation and prevention. nCapp also contributes to the long-term follow-up of patients with COVID-19. The ultimate goal is to enable different levels of COVID-19 diagnosis and treatment among different doctors from different hospitals to upgrade to the national and international through the intelligent assistance of the nCapp system. In this way, we can block disease transmission, avoid physician infection, and epidemic prevention and control as soon as possible.

Background Epstein-Barr virus (EBV) is implicated in the progression of chronic obstructive pulmonary disease. We aimed to determine whether EBV correlates with bronchiectasis severity, exacerbations, and progression. Methods We collected induced sputum in healthy controls and spontaneous sputum at 3–6-month intervals and onset of exacerbations in bronchiectasis patients between March 2017 and October 2018. EBV DNA was detected with quantitative polymerase chain reaction. Results We collected 442 sputum samples from 108 bronchiectasis patients and 50 induced sputum samples from 50 healthy controls. When stable, bronchiectasis patients yielded higher detection rates of EBV DNA (48.1% vs 20.0%; P = .001), but not viral loads (mean log10 load, 4.45 vs 4.76; P = .266), compared with controls; 64.9% of patients yielded consistent detection status between 2 consecutive stable visits. Neither detection rate (40.8% vs 48.1%; P = .393) nor load (mean log10 load, 4.34 vs 4.45; P = .580) differed between the onset of exacerbations and stable visits, nor between exacerbations and convalescence. Neither detection status nor viral loads correlated with bronchiectasis severity. EBV loads correlated negatively with sputum interleukin-1β (P = .002), CXC motif chemokine-8 (P = .008), and tumor necrosis factor–α levels (P = .005). Patients initially detected with, or repeatedly detected with, EBV DNA had significantly faster lung function decline and shorter time to next exacerbations (both P < .05) than those without. Detection of EBV DNA was unrelated to influenza virus and opportunistic bacteria (all P > .05). The EBV strains detected in bronchiectasis patients were phylogenetically homologous. Conclusions Patients with detection of EBV DNA have a shorter time to bronchiectasis exacerbations. EBV may contribute to bronchiectasis progression., The role of chronic viral infections in bronchiectasis is unclear. In this prospective study, we summarize the association between viral loads or detection rate and the clinical status as well as inflammatory response of bronchiectasis.

The aim of our study was to elucidate the landscapes of genetic alterations of TSC1 and TSC2 as well as other possible non-TSC1/2 in Lymphangioleiomyomatosis (LAM) patients. Sixty-one Chinese LAM patients' clinical information was collected. Tumor biopsies and matched leukocytes from these patients were retrospectively analyzed by next generation sequencing (NGS), chromosomal microarray analysis (CMA), and multiplex ligation-dependent probe amplification (MLPA). Eighty-six TSC1/2 variants were identified in 46 of the 61 LAM patients (75.4%) in which TSC2 and TSC1 variants were 88.37% and 11.63% respectively. The 86 variants are composed of (i) 52 single nucleotide variants (SNVs) (including 30 novel variants), (ii) 23 indels (including 21deletions, and 2 insertions), (iii) a germline duplication of exon 31-42 of TSC2, (iv) a 2.68 Mb somatic duplication containing TSC2, and (v) 9 regions with copy-neutral loss of heterogeneity (CN-LOHs) present only in the LAM patients with single TSC1/2 mutations. Sixty-one non-TSC1/2 variants in 31 genes were identified in 37 LAM patients. Combined applications of different techniques are necessary to achieve maximal detection rate of TSC1/2 variants in LAM patients. Thirty novel TSC1/2 variants expands the spectrum of TSC1/2 in LAM patients. Identification of 61 non-TSC1/2 variants suggests that alternative genes might have contributed to the initiation and progression of LAM.

Interleukin (IL)-17A plays a critical role in the pathogenesis of allergic airway inflammation. Yet, the exact roles of IL-17A in asthma are still controversial. Thus, the aim of this study was to dissect the roles of IL-17A in toluene diisocyanate (TDI)-induced mixed granulocytic asthma and to assess the effects of neutralizing antibody in different effector phases on TDI-induced asthma.IL-17A functions in allergic airway inflammation were evaluated using mice deficient in IL-17A (TDI-induced mixed granulocytic airway inflammation was IL-17A-dependent because airway hyperreactivity, neutrophil and eosinophil infiltration, airway smooth muscle thickness, epithelium injury, dysfunctional T helper (Th) 2 and Th17 responses, granulocytic chemokine production and mucus overproduction were more markedly reduced in theOur data demonstrated that IL-17A was required for the initiation of TDI-induced asthma, but functioned as a negative regulator of established allergic inflammation, suggesting that early abrogation of IL-17A signaling, but not late IL-17A neutralization, may prevent the progression of TDI-induced asthma and could be used as a therapeutic strategy for severe asthmatics in clinical settings.

Background Few studies have analyzed influenza B virus lineages based on hemagglutinin A (HA) gene sequences in southern China. The present study analyzed the HA gene and the lineages of influenza B virus isolates from Guangzhou during 2016, and compared our results with the WHO-recommended vaccine strain. Methods Ninety patients with influenza B were recruited from the First Hospital of Guangzhou Medical University. Throat swab specimens of 72 patients had high viral loads. Among these 72 isolates, the HA1 domain of the HA gene in 43 randomly selected isolates was sequenced using reverse transcription-polymerase chain reaction (RT-PCR), and analyzed using MEGA 5.05. Results Eight of the 90 patients (8.9%) also had influenza A virus infections. Analysis of the 43 influenza B virus isolates indicated that 34 (79.1%) were from the Victoria lineage and 9 (20.9%) were from the Yamagata lineage. A comparison isolates in our Victoria lineage with the B/Brisbane/60/2008 strain indicated 12 mutation sites in the HA1 domain, 4 of which (I132V, N144D, C196S, and E198D) were in antigenic epitopes. A comparison of isolates in our Yamagata lineage with the B/Phuket/3073/2013 stain indicated 5 mutation sites in the HA1 domain, none of which was in an antigenic epitope. None of the isolates had a mutation in regions of the neuraminidase gene (NA) that are known to confer resistance to NA inhibitors. Conclusion In Guangzhou during 2016, most influenza B virus isolates were from the Victoria lineage, in contrast to the vaccine strain recommended by the WHO for this period. Electronic supplementary material The online version of this article (10.1186/s12985-018-1085-5) contains supplementary material, which is available to authorized users.

Brian J Lipworth,1 David J Collier,2 Yasuhiro Gon,3 Nanshan Zhong,4 Koichi Nishi,5 Rongchang Chen,4 Samir Arora,6 Andrea Maes,7 Shahid Siddiqui,8 Colin Reisner,7,8 Ubaldo J Martin8 1Scottish Centre for Respiratory Research, Ninewells Hospital, University of Dundee, Dundee, Scotland, UK; 2William Harvey Research Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK; 3Itabashi Hospital, Nihon University School of Medicine, Itabashi, Tokyo, Japan; 4Guangzhou Institute of Respiratory Health, State Key Laboratory of Respiratory Diseases, National Clinical Research Center of Respiratory Diseases, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, People’s Republic of China; 5Ishikawa Prefectural Central Hospital, Kanazawa, Ishikawa, Japan; 6Aventiv Research Inc., Columbus, OH, USA; 7Pearl – a member of the AstraZeneca group, Morristown, NJ, USA; 8AstraZeneca, Gaithersburg, MD, USA Background: COPD is a major global cause of mortality and morbidity. PINNACLE-4 evaluated the efficacy and safety of GFF MDI (glycopyrrolate/formoterol fumarate metered dose inhaler) in patients from Asia, Europe, and the USA with moderate-to-very severe COPD. Methods: In this double-blind, placebo-controlled, Phase III study, patients were randomized to treatment with GFF MDI 18/9.6µg, glycopyrrolate (GP) MDI 18µg, formoterol fumarate (FF) MDI 9.6µg, or placebo MDI (all twice daily) for 24weeks. Lung function, patient-reported outcomes (symptoms and health-related quality of life), and safety were assessed. Results: Of the 1,756 patients randomized, 1,740 patients were included in the intent-to-treat population (mean age 64.2years, 74.1% male, and 40.2% Asian). GFF MDI significantly improved morning predose trough FEV1 at Week 24 (primary endpoint) vs placebo MDI, GP MDI, and FF MDI (least squares mean differences: 165, 59, and 72mL, respectively; all P

Bronchiectasis is a debilitating chronic inflammatory airway disease which arises from multiple etiologies. The interplay among the etiology, altered microenvironment and defective host-defense may have predisposed to recurrent chest infections of pathogens (1,2) that correlate with bronchiectasis exacerbations and increased mortality.

Background: Interstitial lung disease (ILD) is a slowly progressing fatal fibrotic lung disease with a widely variable clinical course and a poor prognosis. Clinicians and patients would benefit from a highly efficient and accurate predictor for ILD. The purpose of this study was to evaluate whether blood biomarkers can predict ILD progression. Methods: In this study, 85 patients diagnosed as having ILD at the Guangzhou Institute of Respiratory Health participated, including 20 patients with idiopathic pulmonary fibrosis (IPF). During the mean follow-up time of 12 months, every patient was examined during four or five visits in our center. Serum samples were collected at baseline, and after 1, 2, 6, and 12 months and tested for the Klebs von den Lungen-6 (KL-6) concentration. Dynamic fluctuations in this biomarker concentration were examined using a logistic regression model to see if they reflected the progression of ILD. Results: The baseline levels of serum KL-6 in the ILD patients were significantly increased compared to healthy controls. Serum KL-6 levels were significantly elevated in patients with progression of disease (1,985.2±1,497.8 vs . 1,387.6±1,313.1 µg/mL; P Conclusions: Serum levels of KL-6 were elevated in ILD patients with severe respiratory function compared to those without. The rate of poor prognosis and mortality was associated with increased biomarker concentrations. Sequential measurements of biomarkers could be valuable in disease monitoring and evaluations in clinical management.

Two new flavonoid–triterpene saponin meroterpenoids, clinoposides G (1) and H (2) were isolated from the aerial parts of Clinopodium chinense (Benth.) O. Kuntze. Their structures were elucidated through spectroscopic and electronic circular dichroism (ECD) analyses. Compounds 1 and 2 were evaluated for their protective effects against anoxia/reoxygenation(A/R)-induced injury in H9c2 cells. A/R treatment severely injured the H9c2 cells, which was accompanied by apoptosis. Both 1 and 2 pretreatment significantly inhibited cell injury and apoptosis, improved mitochondrial membrane potential, increased activities of antioxidant enzymes, and reduced the levels of the inflammatory cytokines. In addition, the presence of 1 and 2 significantly decreased the protein level of p65 and increased the level of Nrf2 in cell nucleus. Unique chemical structure and good biological activity of 1 and 2 elucidated the potential of meroterpenoids as a promising reagent for treating heart disease.

This study correlated serial blood transcriptomic profiles of patients with avian influenza A (H7N9) virus infection with clinical data of patients. Biologically significant transcriptomic profiles associated with blood oxygenation and viral load in the lower respiratory tract were defined., Background Avian influenza A (H7N9) viruses emerged in China in 2013 and caused zoonotic disease associated with a case-fatality ratio of over 30%. Transcriptional profiles in peripheral blood reflect host responses and can help to elucidate disease pathogenesis. Methods We correlated serial blood transcriptomic profiles of patients with avian influenza A (H7N9) virus infection and determined the biological significances from the analysis. Results We found that specific gene expression profiles in the blood were strongly correlated with the Pao 2/Fio 2 ratio and viral load in the lower respiratory tract. Cell cycle and leukocyte-related immunity were activated at the acute stage of the infection while T-cell functions and various metabolic processes were associated with the recovery phase of the illness. A transition from systemic innate to adaptive immunity was found. Conclusions We developed a novel approach for transcriptomic analysis to identify key host responses that were strongly correlated with specific clinical and virologic parameters in patients with H7N9 infection.

Lili Guan,1,* Jiawen Xu,1,* Weiliang Wu,1,* Jianhua Chen,1,* Xiaoying Li,2,* Bingpeng Guo,1 Yuqiong Yang,1 Yating Huo,1 Luqian Zhou,1 Rongchang Chen1 1State Key Laboratory of Respiratory Disease, Guangzhou Institute of Respiratory Disease, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China; 2The First Affiliated Hospital, School of Clinical Medicine of Guangdong Pharmaceutical University, Guangzhou, China *These authors contributed equally to this work Purpose: Patients with advanced-stage COPD often experience severe hypoxemia. Treatment with long-term oxygen therapy (LTOT) may relieve patients’ symptoms and increase survival. As COPD is incurable, improving patients’ health-related quality of life is important. The Chinese version of the Severe Respiratory Insufficiency Questionnaire (SRI) is valid for patients with hypercapnic COPD undergoing noninvasive positive airway pressure ventilation at home. However, the reliability and validity of the Chinese SRI for patients with COPD undergoing LTOT have not been investigated. Patients and methods: We analyzed reliability using Cronbach’s α coefficient. Construct validity was assessed with principal, exploratory, and confirmatory factor analysis. Concurrent validity was evaluated through the correlation between SRI domains and Chronic Respiratory Disease Questionnaire (CRQ) domains. Content validity was assessed by calculating the correlation between each SRI item score and the total score for the relevant domain. Results: In total, 161 patients participated in this study. The Cronbach’s α coefficient for all SRI domains was >0.7, except for the attendant symptoms and sleep domain. Exploratory and confirmatory factor analysis showed a good model fit for each domain, but the factors extracted from each domain were correlated. SRI and CRQ domains correlated well with respect to similar aspects of health-related quality of life, indicating good concurrent validity. Content validity was indirectly shown by a good correlation between each item score and the total score of the relevant domain. Conclusion: The Chinese version of the SRI has a good reliability and validity for patients with COPD undergoing LTOT in China. Keywords: severe respiratory insufficiency questionnaire, long-term oxygen therapy, health-related quality of life, chronic obstructive pulmonary disease

Yating Huo, Lili Guan, Jiawen Xu, Luqian Zhou, Rongchang Chen State Key Laboratory of Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China Background: Airway remodeling is an important feature of chronic obstructive pulmonary disease (COPD) that is associated with disease severity and irreversible airflow limitation. An extensive alteration of the extracellular matrix (ECM) surrounding the airway smooth muscle (ASM) bundle is one of the pathological manifestations of airway remodeling, which contributes to the decline in lung function. Tiotropium, a long-acting inhaled muscarinic receptor antagonist, has been confirmed to play a role in preventing airway remodeling including ECM deposition beyond bronchodilation in vivo, but the relationship between ASM cell (ASMC) relaxation and ECM production remains unclear. Purpose: In this study, we attempted to investigate the influence of tiotropium on ECM production by ASMCs and the underlying mechanism. Methods: Tiotropium was added 30 minutes before the addition of methacholine to primary cultured human ASMCs. Protein expression was analylized by Western Blot and mRNA abundance was determined by real-time PCR. Results: We found that tiotropium reduced collagen I protein expression, and the mRNA abundance of collagen I, fibronectin, and versican. β-catenin signaling was inactivated by inhibiting glycogen synthase kinase 3β (GSK3β) phosphorylation in this process. Tiotropum inhibited the amount of active β-catenin and its transcription activity. Furthermore, overexpression of active β-catenin by adenoviruses carrying the S33Y mutant resisted the suppressive effect of tiotropium on collagen I protein expression. However, silencing β-catenin by specific small interfering RNA enhanced the negative effect of tiotropium. Conclusion: These findings suggest that relaxation of ASMCs by tiotropium can prevent ECM production through β-catenin signaling. Keywords: tiotropium, collagen I, β-catenin, airway smooth muscle cell