Effects of microRNA-21 on endothelial-to-mesenchymal transition and its role in the pathogenesis of chronic obstructive pulmonary disease. / MicroRNA-21å¯¹å† çš®-间å è´¨è½¬åŒ–çš„å½±å“åŠå ¶åœ¨æ ¢æ€§é˜»å¡žæ€§è‚ºç–¾ç— å‘ç— æœºåˆ¶ä¸­çš„ä½œç”¨.

OBJECTIVES: Chronic obstructive pulmonary disease (COPD) is a disease characterized by persistent airflow restriction. This study aims to explore whether there is endothelial-to-mesenchymal transition (EndMT) in COPD mice and to explore the relationship between microRNA-21 (miR-21) and EndMT. METHODS: We established the COPD and the miR-21 gene knockout COPD animal model (both cigarette smoke-induced). Mice were divided into 3 groups (n=4): a control group, a COPD group, and a miR-21 knockout COPD (miR-21-/--COPD) group. Masson trichrome staining was used to observe the deposition of collagen around the perivascular. The relative protein levels and positions of endothelial cell markers including vascular endothelial-cadherin (VE-cadherin), endothelial nitric oxide synthase (eNOS), and platelet endothelial cell adhesion molecule-1 (CD31) as well as mesenchymal cell markers including α-smooth muscle actin (α-SMA) and neural cadherin (N-cadherin) in lung tissues were observed by immunohistochemical staining. RESULTS: Compared with the control group, the area of collagen fibril deposition was increased in the COPD group (P<0.05), the expression levels of VE-cadherin, eNOS, and CD31 were all decreased (all P<0.05), and the expression levels of α-SMA and N-cadherin were increased (both P<0.05). Compared with the COPD group, the miR-21-/--COPD group had a reduced area of collagen fiber deposition (P<0.05), the expression levels of VE-cadherin, eNOS, and CD31 were all increased (all P<0.05), and the expression levels of α-SMA and N-cadherin were decreased (both P<0.05). CONCLUSIONS: There is a EndMT process in cigarette smoke-induced COPD animal models.MiR-21 gene knockdown could reduce collagen deposition area and inhibit the EndMT process in COPD mice.

Progress in the effect of microRNA-21 on diseases via autophagy. / MicroRNA-21é€šè¿‡è‡ªå™¬å½±å“ç–¾ç— çš„ç ”ç©¶è¿›å±•.

Autophagy is a regulatory mechanism that packages damaged organelles, proteins, and pathogens to form vesicles and transports to lysosomes for degradation, enabling the recycle of useful components. Therefore, autophagy plays an important role in biological growth regulation and homeostasis. In the past two decades, growing evidence has shown that microRNA (miRNA) is closely related to autophagy. MiRNA-21 promotes or inhibits autophagy via regulating relevant pathways for different downstream target genes, and plays a role in tumors, ischemia-reperfusion injury, and other diseases.

Efficacy and safety of tratinterol hydrochloride tablets in bronchial asthma: a randomized double-blind and multicenter clinical trial.

PURPOSE: The aim of this study was to investigate the efficacy and safety of tratinterol hydrochloride in bronchial asthma (BA) treatment. METHODS: Patients enrolled in this study were distributed randomly into a treatment group (tratinterol hydrochloride) and an active control group (procaterol hydrochloride) and were treated for 2 weeks after running-in. The end points were changes in pulmonary function and clinical symptoms after administration. Safety indices were physical examinations, laboratory testing and spontaneous reporting. FINDINGS: We enrolled 732 subjects, -365 in the treatment group and 367 in the active control group. Forced expiratory volume (FEV1), significantly increased in both group after treatment (P < 0.05). Least-squares (LS) means were -0.03/in the full-analysis set (FAS) and -0.02 in the per-protocol set (PPS) set, and 95% confidence intervals (CIs) for these sets were -0.09 to 0.03 and -0.08 to 0.04, respectively. Forced expiratory volume (FVC), morning peak expiratory flow (PEF) and asthma scores were significantly different with pretreatment (P < 0.05). There was no difference in asymptomatic days or frequency of relief medicine use (P > 0.05). No serious adverse events occurred. IMPLICATIONS: Tratinterol hydrochloride was effective, safe and not inferior to procaterol hydrochloride in treating BA.

SIRT1 attenuates endoplasmic reticulum stress and apoptosis in rat models of COPD.

The present study aimed to investigate the protective role of sirtuin 1 (SIRT1) and oxygen regulated protein 150 (ORP150) in a rat COPD model by inducing changes in ER stress and apoptosis. We separated 48 Sprague Dawley (SD) rats into four groups randomly: the control group, resveratrol group, COPD group and the resveratrol intervention group. Rats were challenged with cigarette smoke and lipopolysaccharide with resveratrol (a selective activator of SIRT1). The lung functions of the rats were measured and recorded. The expression levels of SIRT1 and ORP150 in lung tissues were examined by western blot and RTq PCR. The expression levels of the ER stress apoptosis-associated protein were determined .The apoptotic level of lung tissues was analyzed. The results suggest that SIRT1 attenuated apoptosis and ER stress in the lung tissues of rats with COPD. During this process, a positive correlation was identified between SIRT1 and ORP150.

Marginal zone lymphoma associated amyloidosis: A case report and literature review. / è¾¹ç¼˜åŒºæ·‹å·´ç˜¤åˆå¹¶æ·€ç²‰æ ·å˜æ€§1ä¾‹åŠæ–‡çŒ®å¤ä¹ .

The marginal zone lymphoma is a common indolent malignant tumor in the blood system, but the patients with myocardial amyloidosis is rare. In January 2018,a marginal zone lymphoma associated with myocardial amyloidosis was accepted by the Third Xiangya Hospital, Central South University, main complaining of shortness of breath for more than half a year.The patient manifested with multiple serous effusion, positive for IgM κ-type M protein, and myocardial amyloidosis. Bone marrow puncture suggested as mature small lymphocyte proliferative disease, and the bone marrow biopsy eventually diagnosed as marginal zone lymphoma involving the bone marrow. The treatment of this disease includes rituzumab, radiochemotherapy and hematopoietic stem cell transplantation.Due to the lack of sepcificity in sympotoms,it is necessary to rely on histopathological biopsy and immunohistochemistry to confirm the diagnosis. The disease is easily missed or misdiagnosed and the prognosis is poor.

Medical students' mental health, professional pride, and intention to work in the front-line during coronavirus disease 2019 pandemic. / 2019å† çŠ¶ç— æ¯’ç— å¤§æµè¡ŒæœŸé—´åŒ»å­¦ç”Ÿå¿ƒç†å¥åº·ã€èŒä¸šè‡ªè±ªæ„Ÿä¸Žä¸€çº¿å·¥ä½œæ„æ„¿.

OBJECTIVES: To understand medical students' mental health, professional pride, and intention to work in the front-line during coronavirus disease 2019 (COVID-19) pandemic, and provide a reference for psychological intervention. METHODS: We used the depression-anxiety-stress scale and self-designed questionnaire on professional pride, intention to work in the front-line and the extent of family support. Medical students from 4 medical schools in Fujian and Hunan were investigated. Their mental health status, professional pride and first-line work willingness with different characteristics were compared, and the influential factors for professional pride and first-line work willingness were analyzed. RESULTS: A total of 266 valid questionnaires were collected. During the pandemic, there were significant differences in the proportion of depressed students among different college and universities, majors and stages (P<0.05), and the professional pride was significantly different (P<0.001). Medical students with different mental health status showed significant differences in professional pride (P<0.01). Marriage, pressure and extent of family support were the influential factors for their professional pride (P<0.05). The latter two were also influential factors for their intention to work in the front-line (P<0.05). CONCLUSIONS: During the pandemic, students from college and nursing have relatively better mental health and higher professional pride. The professional pride is low in medical students who married, with abnormal stress or low family support. The intention to work in front-line is decreased in students with abnormal stress or low family support.

Bronchial epithelial cell extracellular vesicles ameliorate epithelial-mesenchymal transition in COPD pathogenesis by alleviating M2 macrophage polarization.

Chronic obstructive pulmonary disease (COPD) is partly characterized as epithelial-mesenchymal transition (EMT)-related airflow limitation. Extracellular vesicles (EVs) play crucial roles in the crosstalk between cells, affecting many diseases including COPD. Up to now, the roles of EVs in COPD are still debated. As we found in this investigation, COPD patients have higher miR-21 level in total serum EVs. EMT occurs in lungs of COPD mice. Furthermore, bronchial epithelial cells (BEAS-2B) could generate EVs with less miR-21 when treated with cigarette smoke extract (CSE), impacting less on the M2-directed macrophage polarization than the control-EVs (PBS-treated) according to EVs miR-21 level. Furthermore, the EMT processes in BEAS-2B cells were enhanced with the M2 macrophages proportion when co-cultured. Collectively, these results demonstrate that CSE-treated BEAS-2B cells could alleviate M2 macrophages polarization by modulated EVs, and eventually relieve the EMT process of BEAS-2B cells themselves under COPD pathogenesis, revealing a novel compensatory role of them in COPD.

MicroRNA-21 aggravates chronic obstructive pulmonary disease by promoting autophagy.

MicroRNAs and autophagy play important roles in chronic obstructive pulmonary disease (COPD). This study was designed to explore the role of microRNA-21 (miR-21) induced autophagy in COPD. Using the C57BL/6, miR-21-/- mice and human bronchial epithelial (16HBE) cell line, we found that in the lung tissues of mice, the level of autophagy in the COPD model group was significantly higher than that in the control group. However, compared to the COPD model, the level of autophagy was significantly lower in the miR-21-/- CSE+CS group. In the COPD model, miR-21 was overexpressed. Moreover, in human bronchial epithelial (16HBE) cells exposed to cigarette smoke extract (CSE), miR-21 expression was upregulated and autophagy was notably increased. In addition, pretreatment of 16HBE cells with miR-21 inhibitor significantly inhibited autophagy activity and decreased apoptosis, indicating that miR-21 is involved in CSE-induced autophagy and apoptosis. The results showed that miR-21 could increase autophagy and promote the apoptosis of 16HBE cells in COPD. This information contributes to our further understanding of COPD.

[Effect of miR-21 on autophagy, proliferation and apoptosis of macrophages induced by cigarette smoke extract].

OBJECTIVE: To explore the effects of miR-21 on macrophage autophagy, proliferation and apoptosis induced by cigarette smoke extract (CSE).
 Methods: The cells was divided into a control group, a CSE interventine macrophage group (CSE group), and a miR-21 inhibitor+CSE intervention macrophage group (miR-21 inhibitor+CSE group). The expression of miR-21 in the 3 groups was detected by real-time PCR. The effects of miR-21 inhibitor on macrophage autophagy, proliferation and apoptosis were detected by Western blot, MTT assay and flow cytometry.
 Results: Compared with the control group, the levels of miR-21 and autophagy in the CSE group were significantly increased (both P<0.05). The expression of miR-21 in the miR-21 inhibitor+CSE group was significantly lower than that in the CSE group (P<0.05). Compared with the control group, the expressions of macrophage microtubule associated protein 1 light chain 3 alpha (LC3) and autophagy related 7 (ATG7) in the CSE group were increased, which was attenuated by miR-21 inhibitor. Compared with the control group, the macrophage proliferation in the CSE group was inhibited by the miR-21, which could be reversed by adding miR-21 inhibitor; the proliferative rates in the miR-21 inhibitor+CSE group in 2, 3 or 4 days were increased by 1.41, 1.54 or 1.70 times compared with those in the CSE group (all P<0.05). Flow cytometry showed that the apoptosis rate in the control group was (2.57+1.35)%, which was (18.70+2.16)% in the CSE group and (6.28+1.08)% in the miR-21 inhibitor+CSE group (P<0.05).
 Conclusion: CSE intervention macrophage increase the autophagy and apoptosis of macrophages, decrease the cell proliferation by affecting the expression of miR-21 and the level of autophagy in macrophages.

CNTN-1 Enhances Chemoresistance in Human Lung Adenocarcinoma Through Induction of Epithelial-Mesenchymal Transition by Targeting the PI3K/Akt Pathway.

BACKGROUND/AIMS: Chemoresistance has been a major obstacle to the effective treatment of lung cancer. Previously, we found that contactin-1 (CNTN-1) is related to cisplatin resistance in lung adenocarcinoma. Here, we aimed to investigate the underlying mechanism behind the role of CNTN-1 in cisplatin resistance in lung adenocarcinoma. METHODS: EMT-associated phenotypes, including alterations in cellular morphology and marker (E-cadherin, N-cadherin and Vimentin) expression, were compared between A549 cells and A549/DDP cells (a cisplatin-resistant cell line of lung adenocarcinoma with abnormal CNTN-1 expression) by using real-time time PCR and Western blotting. Other methods, including CNTN-1 overexpression in A549 cells and CNTN-1 knockdown in A549/DDP cells, were also used to investigate the role of CNTN-1 in mediating the EMT phenotype and thr resulting cisplatin resistance and malignant progression of cancer cells in vitro and in vivo. RESULTS: A549/DDP cells exhibited an EMT phenotype and aggravated malignant behaviors. CNTN-1 knockdown in A549/DDP cells partly reversed the EMT phenotype, increased drug sensitivity, and attenuated the malignant progression whereas CNTN-1 overexpression in A549 cells resulted in the opposite trend. Furthermore, the PI3K/Akt pathway was involved in the effects of CNTN-1 on EMT progression in A549/DDP cells, verified by the xenograft mouse model. CONCLUSION: CNTN-1 promotes cisplatin resistance in human cisplatin-resistant lung adenocarcinoma through inducing the EMT process by activating the PI3K/Akt signaling pathway. CNTN-1 may be a potential therapeutic target to reverse chemoresistance in cisplatin-resistant lung adenocarcinoma.

[Progress in study on animal models of chronic obstructive pulmonary disease].

Chronic obstructive pulmonary disease (COPD) is an incompletely reversible chronic airway disease that can be prevented and cured. There is a tendency toward increasing the morbidity and mortality for COPD. Establishment of an animal model for COPD is an important step to explore the pathogenesis of this disease. Presently, a well-recognized COPD animal model is not available. The key points for establishing the COPD animal models, such as selection of animal species, parameters for model evaluation, are constantly updated.

[Expression of miR-21 in peripheral blood serum and mononuclear cells in patients with chronic obstructive pulmonary disease and its clinical significance].

OBJECTIVE: To explore expression of miR-21 in peripheral blood serum and mononuclear cells of patients with chronic obstructive pulmonary disease (COPD), and to discuss the significance and underlying mechanisms.
 METHODS: The subjects were divided into a healthy control group (n=41) and a COPD group (n=49). The miR-21 level was detected by quantitative real-time PCR. The correlations between miR-21 and lung function or forced expiratory volume in one second (FEV1) were analyzed.
 RESULTS: The expression levels of miR-21 in the serum and mononuclear cells in the COPD group were significantly elevated compared with those in the healthy group (P<0.05). The expression of miR-21 was correlated with the lung function of COPD patients. The expression level of miR-21 in the COPD patients was positively correlated with FEV1. 
 CONCLUSION: The upregulation of miR-21 in peripheral blood serum and mononuclear cells of COPD patients may contribute to the pathogenesis of COPD and the severity of this disease.

Efficacy and safety of letosteine in the treatment of sputum thickening and expectoration difficulty in patients with respiratory diseases: a multicenter, randomized, double-masked, double dummy, positive drug parallel controlled trial.

This study aimed to compare the efficacy and safety of letosteine and ambroxol hydrochloride for the treatment of sputum thickening and expectoration difficulty due to either acute or chronic respiratory diseases. Patients (n = 240) were randomized to receive either letosteine + placebo (50 mg thrice daily, Group A) or ambroxol hydrochloride + placebo (30 mg thrice daily, Group B) orally for 5-14 days. The primary outcomes comprised the total effectiveness rate and the total improvement rate. Secondary outcomes included: post-treatment IgA level changes and post-treatment therapeutic evaluation scoring of clinical symptoms. The full analysis set (FAS) comprised 113 patients in Group A and 116 in Group B. The total effectiveness rates were 95.58% for Group A and 95.69% for Group B. The total improvement rates were 99.12% and 99.14% for Group A and Group B, respectively. There were no significant differences between the two groups for any of the primary or secondary outcomes in either the FAS or the per protocol populations (PPS; all P-values > 0.05). Letosteine and ambroxol hydrochloride provided equivalent efficacy and safety in the treatment of sputum thickening and expectoration difficulty due to either acute or chronic respiratory diseases.

A multicentre, randomised, double-blind, double-dummy, parallel-controlled, phase 3 clinical trial assessing the efficacy and safety of intravenous nemonoxacin malate vs. levofloxacin for community-acquired pneumonia in adult patients.

BACKGROUND: Nemonoxacin malate is a novel non-fluorinated quinolone for oral and intravenous (IV) administration. This phase 3, multicentre, randomised, double-blind, double-dummy, parallel-controlled clinical trial (NCT02205112) evaluated the efficacy and safety of IV nemonoxacin vs. levofloxacin for the treatment of community-acquired pneumonia (CAP) in adult patients. METHODS: Eligible patients were randomised to receive 500 mg nemonoxacin or levofloxacin via IV infusion, once daily for 7-14 days. The primary endpoint was the clinical cure rate at the test-of-cure (TOC) visit in the modified intent-to-treat (mITT) population. Secondary efficacy and safety were also compared between nemonoxacin and levofloxacin. RESULTS: Overall, 525 patients were randomised and treated with nemonoxacin (n = 349) or levofloxacin (n = 176). The clinical cure rate was 91.8% (279/304) for nemonoxacin and 85.7% (138/161) for levofloxacin in the mITT population (P > 0.05). The clinical efficacy of nemonoxacin was non-inferior to levofloxacin for treatment of CAP. Microbiological success rate with nemonoxacin was 88.8% (95/107) and with levofloxacin was 87.8% (43/49) (P > 0.05) at the TOC visit in the bacteriological mITT population. The incidence of drug-related adverse events (AEs) was 37.1% in the nemonoxacin group and 22.2% in the levofloxacin group. These AEs were mostly local reactions at the infusion site, nausea, elevated alanine aminotransferase/aspartate aminotransferase (ALT/AST), and QT interval prolongation. The nemonoxacin-related AEs were mostly mild and resolved after discontinuation of nemonoxacin. CONCLUSIONS: Nemonoxacin 500 mg IV once daily for 7-14 days is effective and safe and non-inferior to levofloxacin for treating CAP in adult patients.

Central nervous system efficacy of rezivertinib (BPI-7711) in advanced NSCLC patients with EGFR T790M mutation: A pooled analysis of two clinical studies.

BACKGROUND: Rezivertinib (BPI-7711) is a novel third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) which revealed the systematic and central nervous system (CNS) antitumor activities for EGFR T790M-mutated advanced NSCLC in previous clinical studies and is further analyzed here. METHODS: Eligible patients from the previous phase I and phase IIb studies of rezivertinib were included for pooled analysis. Post-progressive patients who received a prescribed dosage (≥180 mg) of rezivertinib orally once daily were included in full analysis set (FAS), while those with stable, asymptomatic CNS lesions, including measurable and non-measurable ones at baseline were included in CNS full analysis set (cFAS). Patients with measurable CNS lesions were included in CNS evaluable for response set (cEFR). BICR-assessed CNS objective response rate (CNS-ORR), CNS disease control rate (CNS-DCR), CNS duration of response (CNS-DoR), CNS progression-free survival (CNS-PFS), and CNS depth of response (CNS-DepOR) were evaluated. RESULTS: 355 patients were included in FAS, among whom 150 and 45 patients were included in cFAS and cEFR. This pooled analysis showed the CNS-ORR was 32.0% (48/150; 95% CI: 24.6-40.1%) and the CNS-DCR was 42.0% (63/150; 95% CI: 34.0-50.3%) in cFAS, while that in cEFR were 68.9% (31/45; 95% CI: 53.4-81.8%) and 100% (45/45; 95% CI: 92.1-100.0%). In cEFR, the median CNS-DepOR and the mean of CNS-DepOR were -52.0% (range: -100.0 to 16.1%) and -46.8% (95% CI: -55.5 to -38.1%). In cFAS, the median CNS-DoR and CNS-PFS were 13.8 (95% CI: 9.6-not calculable [NC]) and 16.5 (95% CI: 13.7-NC) months. CONCLUSIONS: Rezivertinib demonstrated encouraging clinical CNS efficacy among advanced NSCLC patients with EGFR T790M mutation and CNS metastases.

Cyclin D1 G870A polymorphism and lung cancer risk: a meta-analysis.

Many studies have investigated the association between Cyclin D1 (CCND1) G870A polymorphism and lung cancer risk, but the impact of CCND G870A polymorphism on lung cancer is unclear owing to the obvious inconsistence among those studies. This study aimed to quantify the strength of association between CCND1 G870A polymorphism and lung cancer risk. We searched the PubMed, Embase, and Wangfang databases for articles on studies relating the CCND1 G870A polymorphism to the risk of lung cancer in humans. We estimated summary odds ratios (ORs) with their confidence intervals (CIs) to assess the association. Meta-analyses of total studies showed that CCND1 G870A polymorphism was associated with lung cancer risk under three genetic models (OR(A versus G) = 1.13, 95 % CI 1.03-1.24; OR(AA versus GG) = 1.20, 95 % CI 1.07-1.35; OR(AA versus AG + GG) = 1.23, 95 % CI 1.02-1.50). Meta-analyses of studies with high quality showed that CCND1 G870A polymorphism was associated with lung cancer risk under two genetic models (OR(A versus G) = 1.08, 95 % CI 1.02-1.15; OR(AA versus GG) = 1.17, 95 % CI 1.04-1.32). Subgroup analyses by ethnicity and sensitivity analyses further identified the significant association above. No evidence of publication bias was observed. Meta-analyses of available data show a significant association between the CCND1 G870A polymorphism and lung cancer risk, and CCND1 G870A polymorphic variant A contributes to increased risk of lung cancer.

Curcumin protects against sepsis-induced acute lung injury in rats.

The present study aimed to investigate the effect of curcumin on sepsis-induced acute lung injury (ALI) in rats, and explore its possible mechanisms. Male Sprague-Dawley rats were randomly divided into the following five experimental groups (n = 20 per group): animals undergoing a sham cecal ligature puncture (CLP) (sham group); animals undergoing CLP (control group); or animals undergoing CLP and treated with vehicle (vehicle group), curcumin at 50 mg/kg (low-dose curcumin [L-Cur] group), or curcumin at 200 mg/kg (high-dose curcumin [H-Cur] group).At 6, 12, 24 h after CLP, blood, bronchoalveolar lavage fluid (BALF) and lung tissue were collected. The lung wet/dry weight (W/D) ratio, protein level, and the number of inflammatory cells in the BALF were determined. Optical microscopy was performed to examine the pathologic changes in lungs. Myeloperoxidase (MPO) activity, malondialdehyde (MDA) content, as well as superoxidase dismutase (SOD) activity were measured in lung tissues. The expression of inflammatory cytokines, tumor necrosis factor-alpha (TNF-α), interluekin-8 (IL-8), and macrophage migration inhibitory factor (MIF) were determined in the BALF. Survival rates were recorded at 72 h in the five groups in another experiment. Treatment with curcumin significantly attenuated the CLP-induced pulmonary edema and inflammation, as it significantly decreased lung W/D ratio, protein concentration, and the accumulation of the inflammatory cells in the BALF, as well as pulmonary MPO activity. This was supported by the histopathologic examination, which revealed marked attenuation of CLP-induced ALI in curcumin treated rats. In addition, curcumin significantly increased SOD activity with significant decrease in MDA content in the lung. Also, curcumin caused down-regulation of the inflammatory cytokines TNF-α, IL-8, and MIF levels in the lung. Importantly, curcumin improved the survival rate of rats by 40%-50% with CLP-induced ALI. Taken together, these results demonstrate the protective effects of curcumin against the CLP-induced ALI. This effect can be attributed to curcumin ability to counteract the inflammatory cells infiltration and, hence, ROS generation and regulate cytokine effects.

Diagnostic Significance of Metagenomic Next-Generation Sequencing for Community-Acquired Pneumonia in Southern China.

BACKGROUND: The morbidity and mortality of community-acquired pneumonia are relatively high, but many pneumonia pathogens cannot be identified accurately. As a new pathogen detection technology, metagenomic next-generation sequencing (mNGS) has been applied more and more clinically. We aimed to evaluate the diagnostic significance of mNGS for community-acquired pneumonia (CAP) in the south of China. METHODS: Our study selected CAP patients who visited the 3rd Xiangya Hospital from May 2019 to April 2021. Pathogens in bronchoalveolar lavage fluid (BALF) specimens were detected using mNGS and traditional microbiological culture. mNGS group: detected by both mNGS and BALF culture; control group: detected only by BALF or sputum culture. The diagnostic performance of pathogens and the antibiotic adjustments were compared within mNGS group. RESULTS: The incidence of acute respiratory distress syndrome (ARDS) was 28.3% in the mNGS group and 17.3% in the control group. Within the mNGS group, the positive rate of pathogens detected by mNGS was 64%, thus by BALF culture was only 28%. Pathogens detected by mNGS were consisted of bacteria (55%), fungi (18%), special pathogens (18%), and viruses (9%). The most detected pathogen by mNGS was Chlamydia psittaci. Among the pathogen-positive cases, 26% was not pathogen-covered by empirical antibiotics, so most of which were made an antibiotic adjustment. CONCLUSIONS: mNGS can detect pathogens in a more timely and accurate manner and assist clinicians to adjust antibiotics in time. Therefore, we recommend mNGS as the complementary diagnosis of severe pneumonia or complicated infections.

Efficacy and Safety of Rezivertinib (BPI-7711) in Patients With Locally Advanced or Metastatic/Recurrent EGFR T790M-Mutated NSCLC: A Phase 2b Study.

INTRODUCTION: Rezivertinib (BPI-7711) is a novel third-generation EGFR tyrosine kinase inhibitor (TKI) targeting both EGFR-sensitizing mutations and EGFR T790M mutation. This study aimed to evaluate the efficacy and safety of rezivertinib in patients with locally advanced or metastatic/recurrent EGFR T790M-mutated NSCLC. METHODS: Patients with locally advanced or metastatic/recurrent NSCLC with confirmed EGFR T790M mutation who progressed after first-/second-generation EGFR TKI therapy or primary EGFR T790M mutation were enrolled. Patients received rezivertinib at 180 mg orally once daily until disease progression, unacceptable toxicity, or withdrawal of consent. The primary end point was objective response rate (ORR) assessed by blinded independent central review per Response Evaluation Criteria in Solid Tumors version 1.1. Secondary end points included disease control rate (DCR), duration of response, progression-free survival (PFS), overall survival, and safety. This study is registered with Clinical Trials.gov (NCT03812809). RESULTS: A total of 226 patients were enrolled from July 5, 2019, to January 22, 2020. By the data cutoff date on January 24, 2022, the median duration of follow-up was 23.3 months (95% confidence interval [CI]: 22.8-24.0). The ORR by blinded independent central review was 64.6% (95% CI: 58.0%-70.8%), and DCR was 89.8% (95% CI: 85.1%-93.4%). The median duration of response was 12.5 months (95% CI: 10.0-13.9), and median PFS was 12.2 months (95% CI: 9.6-13.9). The median overall survival was 23.9 months (95% CI: 20.0-not calculated [NC]). Among 91 (40.3%) patients with central nervous system (CNS) metastases, the median CNS PFS was 16.6 months (95% CI: 11.1-NC). In 29 patients with more than or equal to one brain target lesion at baseline, the CNS ORR and CNS DCR were 69.0% (95% CI: 49.2%-84.7%) and 100% (95% CI: 88.1%-100%), respectively. Time to progression of CNS was 16.5 months (95% CI: 9.7-NC). Of 226 patients, 188 (83.2%) had at least one treatment-related adverse event, whereas grade more than or equal to 3 occurred in 45 (19.9%) patients. No interstitial lung disease was reported. CONCLUSIONS: Rezivertinib was found to have promising efficacy and favorable safety profile for patients with locally advanced or metastatic/recurrent NSCLC with EGFR T790M mutation.

Genetic analysis of IREB2, FAM13A and XRCC5 variants in Chinese Han patients with chronic obstructive pulmonary disease.

Recently, variants (rs2568494, rs2869967 and rs3821104) in the IREB2, FAM13A and XRCC5 genes were found to be associated with chronic obstructive pulmonary disease (COPD) in non-Asian populations by genome-wide association study (GWAS) analysis. To evaluate whether variants in these genes are related to COPD in Chinese Han population, we investigated COPD patients of Chinese Han ethnicity from Mainland China. Significant differences in genotypic distributions (χ(2)=6.319, p=0.042 for rs2869967; χ(2)=6.062, p=0.048 for rs3821104) and allele distributions (χ(2)=4.014, p=0.045 for rs2869967; χ(2)=5.607, p=0.018 for rs3821104) were observed between patients and control subjects for variants rs2869967 and rs3821104, whereas no statistically significant associations for genotypic and allelic distribution between IREB2 rs2568494 and COPD phenotype (p>0.05) were identified. Our results support that FAM13A rs2869967 and XRCC5 rs3821104 are associated with COPD in Chinese Han population.