Human umbilical cord mesenchymal stromal cell small extracellular vesicle transfer of microRNA-223-3p to lung epithelial cells attenuates inflammation in acute lung injury in mice.

BACKGROUND: Acute lung injury (ALI), manifested as strong pulmonary inflammation and alveolar epithelial damage, is a life-threatening disease with high morbidity and mortality. Small extracellular vesicles (sEVs), secreted by multiple types of cells, are critical cellular communication mediators and can inhibit inflammation by transferring bioactive molecules, such as microRNAs (miRNAs). Thus, we hypothesized that sEVs derived from mesenchymal stromal cells (MSC sEVs) could transfer miRNAs to attenuate inflammation of lung epithelial cells during ALI. METHODS: C57BL/6 male mice were intratracheally administered LPS (10 mg/kg). Six hours later, the mice were randomly administered with MSC sEVs (40 µg per mouse in 150 µl of saline), which were collected by ultracentrifugation. Control group received saline administration. After 48 h, the mice were sacrificed to evaluate pulmonary microvascular permeability and inflammatory responses. In vitro, A549 cells and primary human small airway epithelial cells (SAECs) were stimulated with LPS with or without MSC sEVs treatment. RESULTS: In vitro, MSC sEVs could also inhibit the inflammation induced by LPS in A549 cells and SAECs (reducing TNF-α, IL-1ß, IL-6 and MCP-1). Moreover, MSC sEV treatment improved the survival rate, alleviated pulmonary microvascular permeability, and inhibited proinflammatory responses (reducing TNF-α, IL-1ß, IL-6 and JE-1) in ALI mice. Notably, miR-223-3p was found to be served as a critical mediator in MSC sEV-induced regulatory effects through inhibition of poly (adenosine diphosphate-ribose) polymerase-1 (PARP-1) in lung epithelial cells. CONCLUSIONS: Overall, these findings suggest that MSC sEVs may offer a novel promising strategy for ALI.

Bone mesenchymal stromal cell-derived small extracellular vesicles inhibit inflammation and ameliorate sepsis via delivery of microRNA-21a-5p.

BACKGROUND AIMS: Sepsis is a potentially life-threatening disease that results from a severe systemic inflammatory response due to infection. Mesenchymal stromal cell-derived small extracellular vesicles (MSC sEVs) are able to transfer bioactive molecules and have been demonstrated to play an important role in the pathophysiological process of sepsis. Herein the authors aimed to investigate the potential role and downstream molecular mechanism of MSC sEVs in sepsis. METHODS: MSC sEVs were acquired by ultracentrifugation and then injected into a cecal ligation and puncture mouse model. The efficacy of MSC sEVs in both in vitro and in vivo models of sepsis was evaluated. RESULTS: MSC sEV therapy improved survival, reduced sepsis-induced inflammation, attenuated pulmonary capillary permeability and improved liver and kidney function in septic mice. In addition, the authors found that microRNA-21a-5p (miR-21a-5p) was highly enriched in MSC sEVs, could be transferred to recipient cells, inhibited inflammation and increased survival in septic mice. Furthermore, the authors demonstrated that MSC sEV miR-21a-5p suppressed inflammation by targeting toll-like receptor 4 and programmed cell death 4. The therapeutic efficacy of MSC sEVs was partially abrogated by transfection with miR-21a-5p inhibitors. CONCLUSIONS: Collectively, the authors' data suggest that miR-21a-5p-bearing MSC sEVs may be a prospective and effective sepsis therapeutic strategy.

Risk factors and mortality of carbapenem-resistant Klebsiella pneumoniae bloodstream infection in a tertiary-care hospital in China: an eight-year retrospective study.

BACKGROUND: The prevalence of carbapenem-resistant Klebsiella pneumoniae bloodstream infection (CRKP-BSI) is increasing worldwide. CRKP-BSI is associated with high rates of morbidity and mortality due to limited antibiotic choices. Here, we aim to identify the prevalence and risk factors for infection and mortality of CRKP BSI. METHODS: This was a retrospective study of the past data from January 1st, 2012 to December 31st, 2019 of adult patients with KP-BSI in Xiangya Hospital, China. RESULTS: Among the 706 incidences included in this study, 27.4% of them (212/753) being CR-KP strains. The occurrence of CRKP-BSI was increased from 20.69 to 37.40% from 2012 to 2019. Hematologic malignancies and ICU acquired infection were identified to be substantial risk factors of carbapenem resistance. The overall 28-day mortality rates of CRKP-BSI patients was significantly higher than that of CSKP-BSI (P < 0.001). Logistic regression analysis identified severe sepsis or septic shock incidents, inadequate empirical antimicrobial therapy and corticosteroids use preceding infection onset as the independent predictors of 28-day mortality of CRKP-BSI patients. However, high dose carbapenem combination therapy was identified as anticipated factors of low 28-day mortality. CONCLUSION: The occurrence of CRKP-BSI was significantly increased during the study period. Hematologic malignancies and ICU acquired infection were associated with the development of CRKP BSI. Severe sepsis or septic shock incidents, inadequate empirical antimicrobial therapy and corticosteroids use preceding infection onset caused significant increase of mortality rates in CRKP-BSI patients. High dose carbapenem combination therapy was associated with better outcome.

Human mesenchymal stromal cells small extracellular vesicles attenuate sepsis-induced acute lung injury in a mouse model: the role of oxidative stress and the mitogen-activated protein kinase/nuclear factor kappa B pathway.

BACKGROUND AIMS: Acute lung injury (ALI) secondary to sepsis is a complex disease associated with high morbidity and mortality. Mesenchymal stem cells (MSCs) and their conditioned medium have been demonstrated to reduce alveolar inflammation, improve lung endothelial barrier permeability and modulate oxidative stress in vivo and in vitro. Recently, MSCs have been found to release small extracellular vesicles (sEVs) that can deliver functionally active biomolecules into recipient cells. The authors' study was designed to determine whether sEVs released by MSCs would be effective in sepsis-induced ALI mice and to identify the potential mechanisms. METHODS: A total of 6 h after cercal ligation and puncture, the mice received saline, sEV-depleted conditioned medium (sEVD-CM) or MSC sEVs via the tail vein. RESULTS: The administration of MSC sEVs improved pulmonary microvascular permeability and inhibited both histopathological changes and the infiltration of polymorphonuclear neutrophils into lung tissues. In addition, the activities of antioxidant enzymes were significantly increased in the group treated with sEVs compared with the saline and sEVD-CM groups, whereas lipid peroxidation was significantly decreased. Furthermore, sEVs were found to possibly inhibit phosphorylation of the mitogen-activated protein kinase/nuclear factor kappa B (MAPK/NF-κB) pathway and degradation of IκB but increase the activities of nuclear factor erythroid 2-related factor 2 and heme oxygenase 1. CONCLUSIONS: These findings suggest that one of the effective therapeutic mechanisms of sEVs against sepsis-induced ALI may be associated with upregulation of anti-oxidative enzymes and inhibition of MAPK/NF-κB activation.

Epidemiological and clinical features in patients with coronavirus disease 2019 outside of Wuhan, China: Special focus in asymptomatic patients.

OBJECTIVES: In December 2019, coronavirus disease 2019 (COVID-19) emerged in Wuhan City and rapidly spread across the world. The clinical characteristics of affected patients in different regions and populations may differ. Thus, this study aimed to identify the characteristics of the disease to provide an insight about the prevention and treatment of COVID-19. METHODS: Data on the demographic characteristics and clinical findings of the patients admitted at the First Hospital of Changsha from January 1, 2020 to February 10, 2020 were assessed. RESULTS: In this study, there were 8 (3.8%) asymptomatic, 21 (10.0%) mild upper respiratory tract infection (URTI), and 180 (86.1%) pneumonia cases. In total, 47 (22.5%) patients resided in Wuhan, and 45 (21.5%) had recently traveled to Wuhan before disease onset. Moreover, 19 (9.1%) had contact with people from Wuhan, and 69 (33.0%) were family cluster cases. The median incubation period was approximately 6.3 (range: 1.0-20.0) days. Fever and cough were the most common initial symptoms: 99 (49.3%) patients presented with fever, without cough; 59 (29.4%) with cough, without fever; and 33 (16.4%) with both fever and cough. CONCLUSION: The symptoms of patients with COVID-19 were relatively mild outside Wuhan, and family cluster was a remarkable epidemic characteristic. Special attention should be paid to asymptomatic patients.

Quantitative evaluation of cellular internalization of polymeric nanoparticles within laryngeal cancer cells and immune cells for enhanced drug delivery.

Clinical translation of poly (lactic-co-glycolic acid) (PLGA)-based nanomedicine is limited, partly because of the poor delivery efficiency resulting from non-specific phagocytosis by phagocytes. Understanding the nanoparticle interplay between cancer cells and immune cells remains largely elusive. In this study, a quantitative investigation on cellular internalization of fluorescent PLGA particles (100 nm, 500 nm, and 1 µm) against laryngeal carcinoma cells with or without monocytes/macrophages in monoculture or co-culture systems was first performed. PLGA particles at concentrations of 5-20 µg/mL show superior biocompatibility except for 500 nm and 1 µm PLGA particles at 20 µg/mL slightly reduce cell viability. Microscopic observation has discovered all three sizes of particles are effectively ingested by both cancer cells and macrophages; however, quantitative fluorescence examination has disclosed that the uptake index of cancer cells (mean intracellular particle fluorescence per cancer cell normalized to that of per macrophage) is substantially declined for all PLGA particles in co-cultures compared to that in monocultures (1.35-1.05, 1.50-0.59, and 1.4-0.47 for 100 nm, 500 nm, and 1 µm particles, respectively). Quantitative analysis using flow cytometry further confirmed the reduced uptake index of cancer cells in co-cultures, but higher particle counts per macrophage. It has also been found that the formation of multinucleated giant cells via the fusion of macrophages increased after PLGA treatment, which could be further exploited as a potential approach for tumor drug delivery. Overall, these findings provide new insights into the interaction of nanoparticle-immune-cancer cells, which may facilitate the application of PLGA-based nanocarriers for the treatment of laryngeal carcinoma.

Chest CT features associated with the clinical characteristics of patients with COVID-19 pneumonia.

OBJECTIVES: Coronavirus disease 2019 (COVID-19) has rapidly swept across the world. This study aimed to explore the relationship between the chest CT findings and clinical characteristics of COVID-19 patients. METHODS: Patients with COVID-19 confirmed by next-generation sequencing or RT-PCR who had undergone more than 4 serial chest CT procedures were retrospectively enrolled. RESULTS: This study included 361 patients - 192 men and 169 women. On initial chest CT, more lesions were identified as multiple bilateral lungs lesions and localised in the peripheral lung. The predominant patterns of abnormality were ground-glass opacities (GGO) (28.5%), consolidation (13.0%), nodule (23.0%), fibrous stripes (5.3%) and mixed (30.2%). Severe cases were more common in patients with a mixed pattern (21.1%) and less common in patients with nodules (2.4%). During follow-up CT, the mediumtotal severity score (TSS) in patients with nodules and fibrous strips was significantly lower than that in patients with mixed patterns in all three stages (p < .01). CONCLUSION: Chest CT plays an important role in diagnosing COVID-19. The CT features may vary by age. Different CT features are not only associated with clinical manifestation but also patient prognosis. Key messages The initial chest CT findings of COVID-19 could help us monitor and predict the outcome. Nodules were more common in non severe cases and had a favorable prognosis. The mixed pattern was more common in severe cases and usually had a relatively poor outcome.

Allergic Bronchopulmonary Aspergillosis With Elevated CEA Is Infrequent / La aspergilosis broncopulmonar alérgica con niveles elevados de antígeno carcinoembrionario (CEA) es infrecuente

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Retraction Note: Inhibition of airway inflammation in a cockroach allergen model of asthma by agonists of miRNA-33b.

This article has been retracted.

Oxidative CaMKII as a potential target for inflammatory disease (Review).

CaMKII is a calcium­activated kinase, proved to be modulated by oxidation. Currently, the oxidative activation of CaMKII exists in several models of asthma, chronic rhinosinusitis with nasal polyps, cardiovascular disease, diabetes mellitus, acute ischemic stroke and cancer. Oxidized CaMKII (ox­CaMKII) may be important in several of these diseases. The present review examines the mechanism underlying the oxidative activation of CaMKII and summarizes the current findings associated with the function of ox­CaMKII in inflammatory diseases. Taken together, the findings of this review aim to improve current understanding of the function of ox­CaMKII and provide novel insights for future research.

Analysis of the Clinical Features of Tracheobronchial Fungal Infections with Tumor-Like Lesions.

BACKGROUND: Tracheobronchial fungal infections (TBFI) cause life-threatening complications in immunocompromised hosts but are rarely reported. Misdiagnosis and delayed antifungal treatment are associated with the high mortality rate of patients with TBFI. OBJECTIVES: This study analyzed the bronchoscopic features of TBFI and their roles in the early diagnosis of TBFI. METHODS: The demographic, clinical, radiologic, and bronchoscopic data of 53 patients diagnosed with TBFI in our department during a 15-year period were retrospectively analyzed. RESULTS: Most of the TBFI patients were male, and mass was the most common radiologic abnormality. Obvious predilection in primary bronchus distributions was observed. 41.9% of the 43 Aspergillus tracheobronchitis (AT) patients, 70% of the 10 tracheobronchial mucormycosis (TM) patients, and 100% of the 3 endobronchial cryptococcosis patients had been misdiagnosed as having cancer on bronchoscopy because of the presence of tumor-like lesions. The most common features of AT were bronchial occlusion with a mass or mucosal necrosis, bronchial stenosis with mucosal hyperplasia, or uneven mucosa. The main descriptions of TM were bronchial stenosis or obstruction due to mucosal necrosis, uneven mucosa, or a mass. The endoscopic characteristics of endobronchial cryptococcosis included occlusion due to uneven mucosa or mass, or external compressive stricture. CONCLUSION: Immunocompromised patients and immunocompetent patients with underlying disease displaying tumor-like lesions on bronchoscopy should be differentially diagnosed with cancer. Bronchial biopsy is indispensable for the early diagnosis of TBFI.

Diagnostic Accuracy of Bronchodilator Response for Asthma in a Population of South China.

INTRODUCTION: A significant bronchodilator response is commonly defined as a 12% or greater and 200 ml or greater change in FEV1 from baseline according to the 2005 American Thoracic Society (ATS)/European Respiratory Society (ERS) criterion. A number of studies have shown that the ATS/ERS criterion has limitations in asthma diagnosis, and some experts have argued for correcting the criteria. The aim of this study is to investigate the diagnostic value of acute bronchodilator response for asthma in a Southern Chinese population. METHODS: We prospectively evaluated 805 patients with obstructive lung disease (309 for asthma, 496 for non-asthma). Spirometry was performed according to the ATS/ERS guidelines. Data were analyzed by SPSS 18.0. The receiver-operating characteristic (ROC) curve was drawn to assess the diagnostic accuracy of the ATS/ERS criterion based on FEV1. Linear regression was used to analyze the factors of FEV1 change. RESULTS: The sensitivity and specificity of the acute bronchodilator test when judged by the ATS/ERS criteria (200 ml or higher and 12% improvement) were 68.6% and 78.2%, respectively. For the ATS/ERS criteria, the Youden Index, which comprehensively reflects the authenticity of a diagnostic test, was 46.8%. The absolute change of FEV1 positively correlated with baseline FEV1 and weight and negatively with age, while the percentage change of FEV1 was negatively correlated with baseline FEV1, age and height and positively with weight. Compared with the different diagnostic values, when ∆FEV1 was 195 ml and ∆FEV1i% was 14%, the Youden Index was the largest (48.2%) and the diagnostic capability of the test the biggest. CONCLUSIONS: The ATS/ERS criterion for acute bronchodilator response might not be completely suitable for asthma in the Chinese population. TRIAL REGISTRATION: Chinese Clinical Trial Registry (Registry ID: ChiCTR-DDT-14004976). FUNDING: This work was supported by the National Natural Science Foundation of China (grant nos. 81670027, 81270080).

Report of 12 cases with tracheobronchial mucormycosis and a review.

OBJECTIVES: Tracheobronchial mucormycosis is a rare and invasive pulmonary mucormycosis involving the tracheobronchial tree. DATA SOURCE: At a 3500-bed tertiary care center. STUDY SELECTION: This was a retroactive study of 12 cases of tracheobronchial mucormycosis diagnosed in our hospital, and 48 cases that were previously reported in the English literature. RESULTS: Rhizopus was the predominant species of pathogen (66.7%). Primary bronchus was the most frequently involved location (38.2%), and upper lobes (51% of cases) were a predilection. Obstructive necrosis and mucosal necrosis were the most common pathological forms (40% and 34.5%, respectively). Fever (59.3%), cough (59.3%), dyspnea (40.7%) and hemoptysis (30.5%) were the most common symptoms. 51.4% patients had rales, 40% had moist rales and 28.6% had negative physical findings. Ninety-five percent patients had immunosuppressive diseases. Diabetes mellitus (66.7%), diabetes ketoacidosis (21.7%), corticosteroid therapy (20%) and kidney insufficiency (18.3%) were the most common predisposing factors. 13.2% had neutropenia which was mostly among the non-diabetic patients (P = .006). Endobronchial lesion of 23.2% had imaging reports with 33.9% exhibiting single mass. Pathological diagnosis of 76.7% used the transbronchial biopsy. The most frequent antifungal therapies were intravenous amphotericin B (79.7%), surgery (33.3%) and surgery combined with amphotericin B therapy (28.3%). Overall in-hospital mortality was 52.5%, with hemoptysis (P = .017), dyspnea at presentation (P = .022) and angioinvasion (P = .03) as independent risk prognostic factors. In contrast, surgery (P = .003) was an independent protection prognostic factor. CONCLUSIONS: Tracheobronchial mucormycosis is a rare but severe disease with high mortality because of its nonspecific clinical presentations and variable predisposing factors.

Inhibition of airway inflammation in a cockroach allergen model of asthma by agonists of miRNA-33b.

MicroRNAs (miRNAs) play powerful roles in immune function by regulating target genes that mediate cell behavior. It is well known that mast cells have essential effector and immune regulatory functions in IgE-associated allergic disorders and in innate and adaptive immune responses. However, the role of miRNAs in mediating mast cell functions and the relevant mechanisms require further exploration. The roles of miR-33b in airway inflammation and mast cell functions are still unknown. To examine the role of miR-33b in mouse mast cells in cockroach allergen-induced asthma, we developed a lentiviral system for miRNA-33b overexpression to examine whether miRNA-33b mediates airway inflammation by regulating mast cell function and to evaluate the underlying mechanism. The results showed that miR-33b inhibited cockroach allergen-induced asthma in vivo: in particular, it inhibited TH2 cytokine production. In addition, we found that in cells in which miRNA-33b had been transfected, mast cell degranulation was inhibited through suppression of the calcium release and IgE/FcεRI pathway. Our study provides new insight into the roles of miR-33b in asthma and mast cell biology and identifies novel mechanisms that may contribute to mast cell-related pathological conditions in airway inflammation.

[Th17/Treg imbalance mediated by IL-8 in RSV-infected bronchial epithelial cells].

OBJECTIVE: To explore the mechanisms for an increase in susceptibility of asthma induced by respiratory syncytial virus (RSV), to observe the expression of interleukin-8 (IL-8) in human bronchial epithelial cells (HBECs) after RSV infection and to invesigate the regulatory effect of IL-8 on Th17/Treg differentiation.
 METHODS: HBECs were divided into a control group and a RSV infected group. The RSVE-infected model of HBECs was established and examined. The expression of IL-8 mRNA was detected by real-time PCR, and the levels of IL-8 were measured by ELISA. Peripheral blood lymphocytes in healthy people were extracted and divided into a control group and an IL-8 treatment group. Based on concentration of IL-8 in RSV-infected HBECs, lymphocytes were treated by a matched concentration of human recombinant IL-8 for 24 h. The distribution of Th17 and Treg subsets in lymphocytes were examined by flow cytometry.
 RESULTS: The RSV-infected HBECs model was successfully established. The infected HBECs were still able to split and passage. The RSV could be detected in every passage in the infected cells. Virus particles indicated by bright yellow green fluorescence were seen under fluorescence microscope. Edema of mitochondrias, expansion of endoplasmic reticulum, fissure around nucleus and intracellular virus particles were all observed under electron microscope. The expression IL-8 mRNA were significantly enhanced in the RSV-infected group, and the level of IL-8 in the RSV-infected group was higher than that in the control group (P<0.05). After IL-8 treatment for 24 h, the ratio of Th17 subsets in lymphocytes were dramatically increased compared to the control group (P<0.05), but there was no difference in the ratio of Treg subsets between the 2 groups (P>0.05).
 CONCLUSION: Over-secretion of IL-8 by the RSV-infected HBECs may promote the differentiation of Th17 subsets and maintain the Th17/Tred imbalance.

A case of solely lung-involved IgG4-related disease mimicking tuberculosis.

IgG4-related disease (IgG4-RD) is a chronic progressive autoimmune disease. Solely lung involved IgG4-RD is extremely rare. Herein, we reported a case of IgG4-related disease as mimicking tuberculosis. A 52-year-old male patient was admitted due to cough and hemoptysis for two months and fever for 1 month. The pre-admission diagnosis in another hospital was secondary pulmonary tuberculosis, but the quadruple anti-tuberculosis therapy was ineffective and the disease condition continued to deteriorate. The percutaneous lung biopsy was carried out after admission and the pathological diagnosis was IgG4-related disease. The patient's disease condition was improved following hormonal therapy.

Differences in distribution and drug sensitivity of pathogens in lower respiratory tract infections between general wards and RICU.

BACKGROUND: Lower respiratory tract infections (LRTIs) are common among patients in hospitals worldwide, especially in patients over the age of 60. This study investigates the differences in distribution and drug sensitivity of pathogens in LRTIs. METHODS: The clinical and laboratory data of 4,762 LRTI patients in the general ward and respiratory intensive care unit (RICU) of Xiangya Hospital (Changsha) were retrospectively analyzed. RESULTS: The infection rate of Gram-negative bacteria was significantly higher than that of Gram-positive bacteria in both the general ward and RICU (P<0.05). The incidence of Gram-negative bacteria infection was significantly higher in the RICU than in the general ward (P<0.05), whereas the incidence of Gram-positive bacteria infection is less in the RICU than in the general ward (P<0.05). In the general ward, the incidence of Gram-negative bacteria infection significantly increased (P<0.05) over time, whereas the incidence of Gram-positive bacteria infection significantly decreased from 1996 to 2011 (P<0.05). In the RICU, the incidence of Gram-positive bacteria infection decreased, while Gram-negative bacteria infections increased without statistical significance (P>0.05). Staphylococcus pneumoniae and Staphylococcus aureus were found to be the predominant Gram-positive strains in the general ward (34.70-41.18%) and RICU (41.66-54.87%), respectively (P>0.05). Pseudomonas aeruginosa and Acinetobacter baumannii were the predominant gram negative strains in the general ward (19.17-21.09%) and RICU (29.60-33.88%), respectively (P>0.05). Streptococcus pneumoniae is sensitive to most antibiotics with a sensitivity of more than 70%. Staphylococcus aureus is highly sensitive to vancomycin (100%), linezolid (100%), chloramphenicol (74.36-82.19%), doxycycline (69.57-77.33%), and sulfamethoprim (67.83-72.46%); however, its sensitivity to other antibiotics is low and decreased each year. Sensitivity of Pseudomonas aeruginosa to most ß-lactam, aminoglycoside, and quinolone group antibiotics decreased each year. CONCLUSIONS: The distribution and drug sensitivity of LRTI pathogens exhibit a high divergence between the general ward and RICU. Streptococcus pneumoniae may not be the predominant pathogen in LRTIs in some areas of China.

[Review of 2 cases of severe infection with pulmonary Strongyloides stercoralis].

OBJECTIVE: To improve the understanding of pulmonary Strongyloides stercoralis. METHODS: Two paients were diagnosed with severe infection with pulmonary Strongyloides stercoralis by respiratory ICU of Xiangya Hospital. The clinical manifestations, laboratory tests, imaging and pathological data were analyzed. Another 87 cases in the literature were reviewed from 1973 to 2013. RESULTS: In the 2 cases, digestive symptoms were the first symptom and Strongyloides stercoralis was found in the lungs. Eosinophils was detected in the 13 death cases by blood routine examination, with 10 cases≤0.05× 10(9)/L. CONCLUSION: The farmers were the main infected people. Patients with basic diseases or with immunosuppression due to long-term glucocorticoid treatment tend to infect and even die after the infection with Strongyloides stercoralis. Eosinophil granulocyte reduction shows poor prognosis, which needs early diagnosis and treatment.

The effect of tai chi on chronic obstructive pulmonary disease: a pilot randomised study of lung function, exercise capacity and diaphragm strength.

BACKGROUND: Although the benefits of exercise on the health of patients with chronic obstructive pulmonary disease (COPD) have been widely reported, the effect of Tai Chi as an alternative exercise has not been thoroughly evaluated in patients with COPD. This study reported a randomised controlled trial, which investigated the effects of Tai Chi on lung function, exercise capacity, and diaphragm strength in patients with COPD. TRIAL DESIGN: Single blind randomised controlled study. SETTING: Department of Respiratory Medicine, Xiangya Hospital, Central South University. METHODS: Forty patients with COPD were randomised into either a control group or Tai Chi intervention group. Participants in the control group received only routine care, while participants in the Tai Chi group received routine care and completed a six-month Tai Chi exercise program. OUTCOMES: Lung function parameters, blood gas parameters, 6-min walking distance (6MWD), and diaphragm strength parameters. RESULTS: Lung function parameters (FEV1: 1.43 ± 0.08 and FEV1 (%) predicted: 47.6 ± 4.76), 6MWD (476 ± 15) and diaphragm strength parameters (TwPes: 1.17 ± 0.07, TwPga: -1.12 ± 0.06, and TwPdi: 1.81 ± 0.09) were found to be significantly increased in participants who successfully completed the six-month Tai Chi program compared to participants in the control group who only received routine care (p<0.05). These parameters were also found to be significantly increased in participants who completed the Tai Chi exercise program compared to the baseline (p<0.05). In contrast, no significant differences in PaO2 and PaCO2 were observed in participants before or after completing a Tai Chi program or between Tai Chi group and control group (p>0.05). CONCLUSIONS: Tai Chi enhances lung function, exercise capacity, and diaphragm strength. However, this is only preliminary research data and a larger trial is needed for more detailed results.

Salubrinal protects against cigarette smoke extract-induced HBEpC apoptosis likely via regulating the activity of PERK-eIF2α signaling pathway.

BACKGROUND AND AIMS: Endoplasmic reticulum (ER) stress plays an important role in cigarette smoke extract (CSE)-induced apoptotic cell death, which is an important pathogenic factor of chronic obstructive pulmonary disease (COPD). The aim of this study was to explore the role of the PERK-eIF2 pathway in CSE-induced human bronchial epithelial (HBE) cell apoptosis and to evaluate the protective effects and possible mechanism of salubrinal (Sal) on CSE-induced HBE cell apoptosis. METHODS: Normal human bronchial epithelial cells (HBEpC) were cultured and then treated with CSE alone or together with Sal or preincubated with or without PERK siRNA. Expressions of p-PERK/PERK, p-eIF2α/eIF2α, and caspase 3 and 4 were detected with PCR, Western blot, and immunofluorescence. Apoptosis was detected using AnnexinV-PI flow cytometry. RESULTS: CSE induced apoptotic cell death and caused a dynamic change in PERK-eIF2α pathway activity following the course of CSE exposure. The knockdown of PERK suppressed the expression of both PERK and p-eIF2a and caused a great increase in cell apoptosis. Sal could eliminate the effects of PERK knockdown, protecting the cells against the CSE insult, and this protection was accomplished through maintaining the homeostasis of PERK- eIF2α pathway. CONCLUSIONS: PERK-eIF2α pathway mediates the CSE-induced HBE cell apoptosis. The intactness of PERK-eIF2α pathway is crucial for HBE cell survival under CSE insult. Sal can protect against CSE-induced HBE cell apoptosis, and this effect is likely achieved through maintaining the homeostasis of PERK- eIF2α pathway.