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Ventilators in the intensive care units (ICU) are life-support devices that help physicians to gain additional time to cure the patients. The aim of the study was to establish a scoring system to evaluate the ventilator performance in the context of COVID-19. The scoring system was established by weighting the ventilator performance on five different aspects: the stability of pressurization, response to leaks alteration, performance of reaction, volume delivery, and accuracy in oxygen delivery. The weighting factors were determined with analytic hierarchy process (AHP). Survey was sent out to 66 clinical and mechanical experts. The scoring system was built based on 54 valid replies. A total of 12 commercially available ICU ventilators providing non-invasive ventilation were evaluated using the novel scoring system. A total of eight ICU ventilators with non-invasive ventilation mode and four dedicated non-invasive ventilators were tested according to the scoring system. Four COVID-19 phenotypes were simulated using the ASL5000 lung simulator, namely (1) increased airway resistance (IR) (10 cm H2O/L/s), (2) low compliance (LC) (compliance of 20 ml/cmH2O), (3) low compliance plus increased respiratory effort (LCIE) (respiratory rate of 40 and inspiratory effort of 10 cmH2O), (4) high compliance (HC) (compliance of 50 ml/cmH2O). All of the ventilators were set to three combinations of pressure support and positive end-expiratory pressure levels. The data were collected at baseline and at three customized leak levels. Significant inaccuracies and variations in performance between different non-invasive ventilators were observed, especially in the aspect of leaks alteration, oxygen and volume delivery. Some ventilators have stable performance in different simulated phenotypes whereas the others have over 10% scoring differences. It is feasible to use the proposed scoring system to evaluate the ventilator performance. In the COVID-19 pandemic, clinicians should be aware of possible strengths and weaknesses of ventilators.

OBJECTIVE To assess the diagnostic value of serum Candida mannan antigen (MN) and anti-mannan IgG and IgM antibodies for candidiasis. METHODS This study was a prospective cohort study. Clinical data and venous blood samples from 23 medical centres in Beijing, China were collected between 1 January 2017 and 31 December 2018. All collected specimens were tested within one week for serum Candida MN and IgG and IgM antibodies using an ELISA kit. RESULTS A total of 452 patients were enrolled, including 188 patients in the Candida exposure groups (56 patients with Candida bloodstream infection, 69 patients with Candida-positive tracheal aspirate cultures and 63 patients with Candida-positive urine cultures) and 264 patients in the control groups (212 healthy controls and 52 patients with bacteraemia). The receiver operating characteristic (ROC) curve of the 56 patients with Candida bloodstream infection and 212 healthy controls showed that serum MN and IgG had good diagnostic value. The area under the ROC curve (AUC) values were 0.812 (95% CI, 0.750-0.873) and 0.866 (95% CI, 0.808-0.924), respectively, wherein the MN specificity and sensitivity were 86.79% and 60.71%, and the IgG were 84.43% and 80.36%, respectively. The AUC of the combination of serum MN and IgG was 0.871(95% CI, 0.813-0.929), and the specificity and sensitivity were 93.87% and 57.14%. CONCLUSIONS The serum levels of Candida MN and its IgG antibody have diagnostic value for Candida bloodstream infection, and combination of MN and IgG can improve diagnostic specificity and may provide a new approach for diagnosis of candidaemia.

BACKGROUND: Chronic pulmonary aspergillosis (CPA) is an underdiagnosed and misdiagnosed disease and now increasingly recognised. However, the diagnosis of CPA remains challenging. In this study, we aimed to investigate the diagnostic values of serum Aspergillus-specific IgG, IgA and IgM antibodies in patients with CPA.METHODS: The prospective study was performed at Chinese People's Liberation Army General Hospital in Beijing, from January 2017 to December 2017. Adult patients with lung lesions presented as cavity, nodule, mass, bronchiectasis or severe fibrotic destruction with at least two lobes in CT imaging were enrolled. One hundred healthy persons were also enrolled as additional controls. The serum levels of Aspergillus-specific IgG, IgA and IgM antibodies and galactomannan (GM) levels were measured simultaneously by plate ELISA kit.RESULTS: A total of 202 patients were enrolled in this study, including 42 CPA patients, 60 non-CPA patients and 100 healthy persons. The most common underlying lung diseases in CPA patients were bronchiectasis (28.6%) and COPD (19.0%). The most common symptoms in the CPA patients were cough (76.2%), sputum (71.4%), and fever (45.2%); chest pain (4.8%) was infrequent. Receiver operating characteristic (ROC) curve analysis revealed that the optimal CPA diagnostic cut-off of Aspergillus-specific IgG, IgA and IgM assays and GM test were 89.3 AU/mL, 8.2 U/mL, 73.3 AU/mL and 0.5μg/L, respectively. The serum levels of Aspergillus-specific IgG and IgA in CPA patients were higher than these in non-CPA patients or healthy persons. The sensitivities and specificities of Aspergillus-specific IgG, IgA, IgM tests and GM test were 78.6 and 94.4%, 64.3 and 89.4%, 50.0 and 53.7% and 71.4 and 58.1%, respectively.CONCLUSIONS: The sensitivity and specificity of serum Aspergillus-specific IgG assay are satisfactory for diagnosing CPA, while the performance of Aspergillus-specific IgA assay is moderate. Aspergillus-specific IgM assay and serum GM test have limited value for CPA diagnosis.TRIAL REGISTRATION: NCT03027089 . Registered 20 January 2017.

Background Chronic obstructive pulmonary disease (COPD) is a disease of continuous progress and environmental factors may affect the progress. COPD patients' activity tolerance and quality of life are associated with air quality. COPD exacerbation from the perspective of geographical air quality has not been reported. Objectives To explore environmental effect of two different geographical places on COPD exacerbation and the effect of cigarette smoke extract and carbon particles on bronchial epithelial cell viability. Methods Total 139 COPD patients, who lived in Beijing during summer and temporarily migrated to Sanya city in winter, have been enrolled. Respiratory symptoms and lung function data were collected when they were living in Beijing or Sanya, respectively. Effect of cigarette smoke extract plus ultrafine carbon particles on airway epithelial cells were studied. Measurements and main results Air pollution as measured by air quality index (AQI) in Beijing summer (113.1±14.2) was significantly worse than that in Sanya winter (49.4±8.9, p

Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to an infection. It is a disease with a high incidence, mortality, and recurrence rate and frequently results in its survivors requiring readmission into hospitals. The readmission is mainly due to recurrent sepsis. Patients with recurrent sepsis are more susceptible to secondary infections partly due to immune dysfunction, leading to a higher mortality in the long term. However, there remains a gap in the understanding of immunological characteristics and underlying mechanisms of recurrent sepsis. In this study, we used mouse models of acute and recurrent sepsis to investigate their different immunological characteristics. And then we subjected the two mouse models to a secondary influenza A virus (H1N1) infection and characterized the different immune responses. Here, we demonstrated that CD4+ T cells present an exacerbated exhaustion phenotype in response to recurrent sepsis as illustrated by the decreased frequency of CD4+ T cells, reduced co-stimulatory CD28 and increased inhibitory PD-1 and Tim-3 expression on CD4+ T cells, increased frequency of regulatory T cells, and reduced MHC-II expression on antigen-presenting cells. Moreover, we showed that antiviral immune responses decrease in the recurrent sepsis mouse model subjected to a secondary infection as illustrated by the reduced pathogen clearance and inflammatory response. This may be a consequence of the exacerbated CD4+ T cell exhaustion. In summary, recurrent sepsis exacerbates CD4+ T cell exhaustion and decreases antiviral immune responses, contributing to significant morbidity, increased late mortality, and increased health care burden in recurrent sepsis patients.

Lung ischemia reperfusion (IR) is known to occur after lung transplantation or cardiac bypass. IR leads to tissue inflammation and damage and is also associated with increased morbidity and mortality. Various receptors are known to partake in activation of the innate immune system, but the downstream mechanism of tissue damage and inflammation is yet unknown. MicroRNAs (miRNAs) are in the forefront in regulating ischemia reperfusion injury and are involved in inflammatory response. Here, we have identified by high-throughput approach and evaluated a distinct set of miRNAs that may play a role in response to IR in rat lung tissue. The top three differentially expressed miRNAs were validated through quantitative PCRs in the IR rat lung model and an in vitro model of IR of hypoxia and reoxygenation exposed type II alveolar cells. Among the miRNAs, miR-18a-5p showed consistent downregulation in both the model systems on IR. Cellular and molecular analysis brought to light a crucial role of this miRNA in ischemia reperfusion. miR-18a-5p plays a role in IR-mediated apoptosis and ROS production and regulates the expression of neuropeptide Galanin. It also influences the nuclear localization of transcription factor: nuclear factor-erythroid 2-related factor (Nrf2) which in turn may regulate the expression of the miR-18a gene. Thus, we have not only established a rat model for lung IR and enumerated the important miRNAs involved in IR but have also extensively characterized the role of miR-18a-5p. This study will have important clinical and therapeutic implications for and during transplantation procedures.

BACKGROUND: To analyze the clinical value of microbiological rapid on-site evaluation (M-ROSE) in the respiratory intensive care unit (RICU) and its impact on the prognosis of critically ill patients. METHODS: We retrospectively included patients who underwent bedside bronchoalveolar lavage in the RICU of Chinese People’s Liberation Army (PLA) General Hospital between January 2017 and December 2020. The patients were divided into M-ROSE and control groups according to whether bedside M-ROSE was performed with to guide the treatment, and for control group, routine treatments were administrated based on all the clinical information. The basic information, treatment methods, test indicators, and prognostic evaluation of the patients were collected and analyzed. RESULTS: A total of 242 patients were enrolled, including 130 patients in the M-ROSE group and 112 patients in the control group. The inflammatory indicators of the patients in the M-ROSE group decreased significantly faster after admission than those of patients in the control group, and the patients in the M-ROSE group used significantly more types of antibiotics [5 (3.0, 5.0)] than those in the control group [3 (2.0, 4.0)] (P

Background The cytological analysis of bronchoalveolar lavage fluid (BALF) plays an essential role in the differential diagnosis of respiratory diseases. In recent years, deep learning has demonstrated excellent performance in image processing and object recognition. Objectives We aim to apply deep learning to the automated interpretation and analysis of BALF. Method Visual images were acquired using an automated biological microscopy platform. We propose a three-step algorithm to automatically interpret BALF cytology based on a convolutional neural network (CNN). The clinical value was evaluated at the patient level. Results Our model successfully detected most cells in BALF specimens and achieved a sensitivity, precision, and F1 score of over 0.9 for most cell types. In two tests in the clinical context, the algorithm outperformed experienced practitioners. Conclusion The program can automatically provide the cytological background of BALF and augment clinical decision-making for clinicians.

Chronic obstructive pulmonary disease (COPD), characterized by progressive airway inflammation and irreversible airflow limitation, leads to serious decline in life quality. The acute exacerbation of COPD (AECOPD) results in high healthcare costs as well as a significant mortality rate. The most common cause of acute exacerbation is infection. Immune deficiency, which induces dysfunction of anti-infection, plays an important role in the pathogenesis of acute exacerbation. As described in this review, the immune dysfunction in patients with AECOPD can be a major focus of efforts to therapeutic strategy.

// Xinying Xue 1, 2 , Yuxia Liu 3 , Yong Wang 1 , Mingming Meng 4 , Kaifei Wang 2 , Xuefeng Zang 5 , Sheng Zhao 6 , Xiaohua Sun 7 , Lei Cui 8 , Lei Pan 1 , Sanhong Liu 9 1 Department of Special Medical Treatment-Respiratory Disease, Beijing Shijitan Hospital, Capital Medical University, Beijing, China 2 Department of Respiratory Diseases of Chinese PLA General Hospital, Beijing, China 3 Department of Research, Peking Union Medical Collage Hospital, Beijing, China 4 Department of Gastroenterology, Beijing Shijitan Hospital, Capital Medical University, Beijing, China 5 Department of Intensive Care Unit, Beijing Shijitan Hospital, Capital Medical University, Beijing, China 6 Department of Cardiology, Peking University Ninth School of Clinical Medicine, Beijing Shijitan Hospital, Beijing, China 7 Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences and Shanghai Jiao Tong University School of Medicine, Shanghai, China 8 Department of Central Laboratory, Beijing Shijitan Hospital, Capital Medical University, Beijing, China 9 Shanghai Institute of Advanced Immunochemical Studies, ShanghaiTech University, Shanghai, China Correspondence to: Lei Pan, email: leipan2010@163.com Sanhong Liu, email: liush@shanghaitech.edu.cn Lei Cui, email: cuileite@aliyun.com Keywords: non-small cell lung carcinoma, miR-21, miR-155, SOCS1, SOCS6 Received: July 11, 2016 Accepted: October 25, 2016 Published: November 02, 2016 ABSTRACT Lung cancer remains the leading cause of cancer-associated death worldwide. MiR-21 and miR-155 are the most amplified miRNAs in non-small cell lung carcinoma (NSCLC), and are critical promoters of NSCLC progression. However, it remains unclear how miR-21 and miR-155 induce cancer progression, and whether these miRNAs share common targets, such as tumor suppressor genes required to prevent NSCLC. Here we report that miR-21 and miR-155 levels are elevated in NSCLC and are proportional to the progression of the disease. In addition, miR-21 and miR-155 share nearly 30% of their predicted target genes, including SOCS1 , SOCS6 , and PTEN , three tumor suppressor genes often silenced in NSCLC. Consequently, antagonizing miR-21, miR-155 or both potently inhibited tumor progression in xenografted animal models of NSCLC. Treatment with miR-21 and miR-155 inhibitors in combination was always more effective against NSCLC than treatment with a single inhibitor. Furthermore, levels of miR-21 and miR-155 expression correlated inversely with overall and disease-free survival of NSCLC patients. Our findings reveal that miR-21 and miR-155 promote the development of NSCLC, in part by downregulating SOCS1 , SOCS6 , and PTEN . Combined inhibition of miR-21 and miR-155 could improve the treatment of NSCLC.

Objectives: To establish a simple, reliable, stable rat C6 glioma model, and to provide an operating platform for studying the pathogenesis and prevention and treatment of glioma. Methods: C6 rat glioma cells were cultured in vitro and cultured in the right caudate putamen of SD rats. After implantation, the survival status of rats was observed and the pathological sections were made. HE is dyeing under light microscope. Results: After 6 days of inoculation of C6 glioma cells, the survival status was good at about 7 days, and the intracranial hypertension was more obvious at about 14 days. Most of them were in the endangered state. In the 18 specimens of the rats, except for the accidental death, the other tumor formation rate was 75%. The tumor structure was obviously displaced with the prolongation of the age of the tumor. HE staining was used to observe the formation of glioma in rat brain. Conclusion: The animal model of C6 glioma is reliable and stable. Its tumor growth characteristics and pathological features are similar to those of human glioma, which can be used as an ideal model for clinical study of glioma.

Sepsis, an infection-induced systemic disease, leads to pathological, physiological, and biochemical abnormalities in the body. Organ dysfunction is caused by a dysregulated host response to infection during sepsis which is a major contributing factor to acute kidney injury (AKI) and the mortality rate for sepsis doubles due to coincidence of AKI. Sepsis-induced AKI is strongly associated with increased mortality and other adverse outcomes. More timely diagnosis would allow for earlier intervention and could improve patient outcomes. Sepsis-induced AKI is characterized by a distinct pathophysiology compared with other diseases and may also have unique patterns of plasma and urinary biomarkers. This concise review summarizes properties and perspectives of the biomarkers for their individual clinical utilization.

Background and Aim Lung cancer is the most commonly diagnosed neoplasm and the leading cause of cancer-related death worldwide. Despite the high incidence of lung cancer, the diagnosis of solitary thin-walled cavity lung cancer is rare. The aim of this review is to explore the potentials of computed tomography (CT) as diagnostic tool for solitary thin-walled cavity lung cancer. Method The literature search was made in electronic databases including PudMed, Ovid SP, Embase, Web of Sciences, EBSCO and Wiley online by using relevant key terms. Because of the rarity of the subject, no precise exclusion or inclusion criteria were used for article selection and the outcome dissemination was decided to be more descriptive rather than quantitative. Results The detection of cavitation in lungs is frequently done utilizing chest radiographs CT scans. However, the diagnostic challenge remains the accurate detection of solitary thin-walled cavity lung cancer among the prevalence of cavitary lung lesions in multiple thoracic disorders including benign disorders, infectious disease and malignant tumors. Moreover, an accurate diagnosis of solitary thin-walled cavity lung cancer is further complicated by its subjective classification within the literature. In order to facilitate early diagnosis of this disease and circumvent the need for more invasive tests that may not be warranted, the overarching goal is to establish definitive radiological features of lung cavities that are indicative of malignancy. Herein, we describe the benefits of using CT to identify and diagnose solitary thin-walled cavity lung cancer, as well as explore the underlying mechanisms that contribute to thin-walled cavity formation in oncology patients. Conclusion CT is the best modality for the noninvasive differentiation between malignant and nonmalignant cavities as it provides reliable information regarding the morphology and density of lesions. Besides, CT densitometry can efficiently detect the calcifications in lesions.

Objective To perform a retrospective comparison of the clinical and radiological features of Klebsiella pneumoniae (KP)-associated and non-KP-associated pyogenic liver abscesses (PLA) in Chinese patients. Methods Patients with confirmed diagnoses of bacterial liver abscess at three Beijing hospitals were enrolled. Clinical isolates from liver abscesses were used to determine serology and expression of hypermucoviscosity genes. Basic clinical, ultrasonographic (US) and computed tomography (CT) data were recorded and compared between patients with KP- and non-KP-associated PLA. Results A total of 101 (77.10%) and 30 (22.90%) cases were due to KP and non-KP pathogens, respectively. Compared with the non-KP cohort, the KP cohort demonstrated a significantly higher incidence of underlying diabetes mellitus, and more gas-forming abscesses, as demonstrated by US and CT examinations. Prior abdominal surgery or chemoradiation therapy was significantly associated with non-KP cases. The non-KP group had a higher chance of a clear edge, compared with the KP group, on pre-contrast CT images. Conclusion KP and non-KP-associated PLA have distinctive risk factors and unique US and CT features, in Chinese patients.

A substantial percentage (8%) of all newly diagnosed cancer cases are in patients with previous tumours, with a similar trend in lung cancer. Cases of multiple primary lung cancer (MPLC) are increasing worldwide, due to improved diagnostic and surveillance mechanisms and the ageing population. Diagnosis of MPLC is complicated by difficulties in distinguishing it from lung cancer metastasis. Clinicopathological assessment, diagnosis and management have evolved, but remain severely limited by the lack of robust and dependable molecular markers for the differential diagnosis of metastasis and MPLC. This systematic review evaluates diagnostic criteria for MPLC, and the subsequent management and success rates. The incorporation of molecular biology techniques into the diagnostic process for MPLC is also discussed.

Objectives To assess retrospectively the diagnostic value of procalcitonin (PCT) in excluding suspected bloodstream infection, establish cut-off values for PCT levels, and compare PCT with other clinical markers. Methods The predictive accuracy of different continuous parameters was estimated by univariate analysis of the area under the receiver operating characteristic curve. Optimized cut-off points for the parameters were selected according to the maximum Youden index values, which in turn were used to define positive and negative predictive values of different parameters in diagnosing bloodstream infection. Results The PCT level yielded a statistically significant area under the receiver operating characteristic curve of 0.765, with a best cut-off value of 0.80 ng/ml (83% sensitivity; 65% specificity, Youden index, J = 0.48). Positive and negative predictive values at this cut-off value were 38% and 94%, respectively. Mann–Whitney U-test revealed significantly higher values for PCT, C-reactive protein and percentage of neutrophils, but not for white blood cell count, in patients with bloodstream infection. Conclusions The serum PCT level can potentially be used as surrogate marker to exclude bacteraemia and to inform critical management decisions regarding antibiotic usage, in patients admitted with suspected bloodstream infection.

Pulmonary arterial hypertension (PAH) is a debilitating condition with progressive remodeling of the pulmonary resistance vessels. PAH is characterized by multifocal, polyclonal lesions inhabited by cells that underwent phenotypic transition, resulting in altered cell proliferation and contractility, ultimately resulting in increased vascular resistance. Diagnosis of PAH is confounded by the fact that it is largely asymptomatic in the initial stages. In fact, idiopathic PAH patients >65 years of age cannot be diagnosed hemodynamically due to high pulmonary capillary wedge pressure. This highlights the need for defining more robust molecular biomarkers for PAH diagnosis and progression. Recent studies have indicated that microRNAs (miRNAs), a class of small noncoding RNAs that regulate gene expression, play a discrete role in vascular inflammation and in the etiology of cardiovascular pathologies inclusive of PAH and can potentially serve as diagnostic biomarkers. However, a cohesive understanding of global miRNA-mediated molecular events that control pulmonary vasculature plasticity is lacking which, if addressed systematically, can lead to detailed elucidation of the downstream cellular pathways that are affected by activation/silencing of silenced cognate transcripts. In turn, this can lead to not only robust biomarkers, but also to novel therapeutic strategies targeting more upstream regulators than the existing ones targeting more downstream effectors. The current review aims to provide a summary understanding of PAH, its associated pathophysiology, current knowledge of the role of miRNAs in PAH, and identifies grey areas that need further research for successful bench-to-bedside transition of these exciting new discoveries.

Quinolones are a group of antimicrobial agents that were serendipitously discovered as byproducts of the synthesis of chloroquine. Chemical modifications, such as the addition of fluorine or piperazine, resulted in the synthesis of third- and fourth-generation fluoroquinolones, with broad-spectrum antimicrobial actions against aerobic or anaerobic, Gram-positive or Gram-negative bacteria. The efficacy and consequent widespread use of quinolones and fluoroquinolones has led to a steady global increase in resistance, mediated via gene mutations, alterations in efflux or cell membranes and plasmid-conferred resistance. The first plasmid-mediated quinolone resistance gene, qnrA1, was detected in 1998. Since then, many other genes have been identified and the underlying mechanisms of resistance have been elucidated. This review provides an overview of quinolone resistance, with particular emphasis on plasmid-mediated resistance.

Background Solitary thin-walled cavity lung cancer is a specific form of lung cancer, the diagnosis of which remains a formidable challenge. Objective By comparing the computed tomography (CT) presentations and pathological findings, the purpose of present study was to explain the possible mechanism of thin-walled cavity formation and to improve the diagnostic accuracy for this disease. Methods The medical records of eighteen patients with solitary thin-walled cavity lung cancer were analyzed retrospectively. Results Chest CT demonstrated that solitary thin-walled cavities located at pulmonary periphery, and all these cavity lesions displayed suspected malignant signs. Pathological findings after surgery confirmed these lesions were adenocarcinoma, most of which were moderately or well differentiated. Microscopic findings showed tumor cells proliferated in the surface of thin-wall cavity in nine patients and infringed bronchiolar wall in five patients. No obvious necrotic tumor cell was observed in each patient. Conclusion It was suggested some thin-walled cavities may be formed as a result of unidirectional check-valve mechanism. Together, a high index of awareness of this suspected CT signs is required for early diagnosis of this disease.

Gefitinib-induced interstitial lung disease (ILD) is a rare but lethal drug adverse event, which usually leads to the withdrawal of gefitinib and causes complications with anticancer treatment. In this study, gefitinib administration combined with prednisolone in a female with stage IIIb non-small cell lung cancer (NSCLC) produced a good outcome without inducing ILD. The results suggested that combined administration of gefitinib with glucocorticoids may be an efficient method to treat NSCLC while avoiding complications with ILD.

Background Several reports have associated Staphylococcus lugdunensis with the incidence of severe infection in humans; however, the frequency and prevalence of this microorganism and thus the propensity of its antimicrobial drug resistance is unknown in China. The objective of the current study was to determine the prevalence of Staphylococcus lugdunensis among six hundred and seventy non-replicate coagulase negative Staphylococcus (CoNS) isolates collected in a 12-month period from clinical specimens in the General Hospital of the People’s Liberation Army in Beijing, China. Results Five (0.7%) of the 670 isolates of CoNS were identified as S. lugdunensis. Whereas three isolates were resistant to erythromycin, clindamycin, and penicillin and carried the ermC gene and a fourth one was resistant to cefoxitin and penicillin and carried the mecA gene, one isolate was not resistant to any of the tested antimicrobials. Pulse field gel electrophoretic analysis did not reveal widespread epidemiological diversity of the different isolates. Conclusion Hence, even though S. lugdunensis may be yet unrecognized and undefined in China, it still might be the infrequent cause of infection and profound multi-drug resistance in the same population.