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.

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.

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.

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.

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.

The inhibitor miR-21 regulates macrophage polarization in an experimental model of chronic obstructive pulmonary disease.

INTRODUCTION: In chronic obstructive pulmonary disease (COPD), macrophages play an indispensable role. In the lung tissues of COPD patients and smokers, macrophages can be observed to polarize towards M2 phenotype. The molecular mechanism of this process is unclear, and it has not been fully elucidated in COPD. METHODS: We bought laboratory animals [C57BL/6 and miR-21-/- C57BL/6(F1)] from the Jackson Laboratory. The model of COPD mice was established by cigarette smoke (CS) exposure combined with intraperitoneal injection of cigarette smoke extract (CSE). RT-PCR detected the expression levels of inflammatory factors and markers associated with M1 and M2 macrophages. The ratio of M2 macrophages to M1 macrophages was detected by immunohistochemical staining. RESULTS: The level of miR-21 was increased in RAW264.7 cells intervened by CSE and in lung tissue and bone marrow-derived macrophages (BMDMs) from COPD mice. CSE can gradually over time increase the level of miR-21. The proportion of M2 macrophages to M1 macrophages had a positive correlation with miR-21. Knockdowning miR-21 can reduce lung tissue damage. CSE also increased the levels of related inflammatory factors and markers associated with M2 macrophages, and an miR-21 inhibitor can reverse this conversion. CONCLUSIONS: We confirmed that CSE can lead to macrophage transformation to the M2 phenotype and an increase in the expression level of miR-21. Knockdown of the miR-21 gene could inhibit the transformation of macrophages to the M2 phenotype in COPD.

CircPTCH1 Promotes Migration in Lung Cancer by Regulating MYCN Expression Through miR-34c-5p.

BACKGROUND: The incidence rate and mortality rate of lung cancer are the highest in the world. Therefore, further studies are needed to reveal the molecular mechanism of lung cancer progression and development. Previous study demonstrated that the deregulation of circRNAs can regulate cell biological functions in tumorigenesis and development. However, the roles of circPTCH1 in lung cancer have not yet been revealed. MATERIALS AND METHODS: The expression levels of circPTCH1, miR-34c-5p, and MYCN were measured by RT-PCR in lung cancer tissues and cells; dual-luciferase reporter and RIP assay showed that circRNA served as a sponge for miRNA, and miRNA could target mRNA. In vitro, effects of si-circPTCH1 can regulate lung cancer cells' migration, invasion were detected by CCK-8 assay, wound healing assay, and transwell assay. RESULTS: Our research demonstrated that the expression of circPTCH1 was upregulated in lung cancer tissues and cell lines and increased in metastatic tissues compared to that of non-metastatic tissues. circPTCH1 sponging miR-34c-5p to target MYCN was revealed by dual-luciferase reporter and a RIP assay. In addition, the expression level of miR-34c-5p was reduced in lung cancer tumor tissues, and MYCN was significantly increased in lung cancer tumor tissues. Pearson correlation analysis showed that miR-34c-5p with circPTCH1 and MYCN had a moderately negative correlation, and there was a moderately positive correlation between circPTCH1 and MYCN. Further, cytological studies found that circPTCH1 reduced lung cancer cells' migration and invasion by targeting MYCN via miR-34c-5p. CONCLUSION: circPTCH1 plays a tumor enhancement role in lung cancer and that can effectively promote migration, invasion and EMT by targeting the miR-34c-5p/MYCN axis. circPTCH1 may be a novel potential treatment and diagnosis biomarker for lung cancer.

MiR-3130-5p is an intermediate modulator of 2q33 and influences the invasiveness of lung adenocarcinoma by targeting NDUFS1.

Genome-wide association studies (GWAS) have reported a handful of loci associated with lung cancer risk, of which the pathogenic pathways are largely unknown. We performed cis-expression quantitative trait loci (eQTL) mapping for 376 lung cancer related GWAS loci in 227 TCGA lung adenocarcinoma (LUAD) and reported two risk loci as eQTL of miRNA. Among the miRNAs in association with lung cancer risk, we further predicted and validated miR-3130-5p as an intermediate modulator of risk loci 2q33 and the tumor suppressor NDUFS1. We assessed the phenotypic impacts of the interaction between miR-3130-5p and NDUFS1 in both lung cancer cell lines and mice xenograft models. As a result, miR-3130-5p directly regulates the expression of NDUFS1 and the corresponding tumor invasiveness, migration and epithelial-mesenchymal transition (EMT). Our findings provide important clues for the pathogenic mechanism of 2q33 in lung carcinogenesis which informs clinical diagnosis and prognosis of LUAD. We performed a cis-eQTL analysis for 376 lung cancer risk loci based on the expression profiles of 251 miRNAs in a cohort of 227 TCGA lung adenocarcinoma. We report a novel pathogenic pathway of 2q33 via miR-3130-5p and NDUFS1.

The effects of the miR-21/SMAD7/TGF-ß pathway on Th17 cell differentiation in COPD.

Chronic obstructive pulmonary disease (COPD) is a complex disease with multiple etiologies, while smoking is the most established one. The present study investigated the modulation of T-helper 17 (Th17) cell differentiation by the miR-21/Smad7/TGF-ß pathway, and their roles in COPD. Lung tissues were obtained from lung cancer patients with or without COPD who underwent lobotomy and the levels of miR-21, TGF-ß/Smad signaling molecules, RORγT, and other Th17-related cytokines were detected. Mouse COPD models were built by exposing both wild-type (WT) and miR-21-/- mice to cigarette smoke (CS) and cigarette smoke extract (CSE) intraperitoneal injection. Isolated primary CD4+ T cells were treated with either CS extract, miR-21 mimics or inhibitors, followed by measuring Th17 cells markers and the expression of TGF-ß/Smad signaling molecules and RORγT. Increased levels of miR-21, Smad7, phosphorylated (p)-Smad2, p-Smad3, TGF-ß, and Th17-related cytokines was detected in the lungs of COPD patients. Lung function in modeled WT mice, but not miR-21-/- ones, deteriorated and the number of inflammatory cells in the lung tissues increased compared to the control WT-mice. Moreover, primary CD4+ lymphocytes tend to differentiate into Th17 cells after the treatment with CSE or miR-21 mimics, and the expression of RORγT and the TGF-ß/Smad signaling were all increased, however miR-21 inhibitors worked reversely. Our findings demonstrated that Th17 cells increased under COPD pathogenesis and was partially modulated by the miR-21/Smad7/TGF-ß pathway.

A randomized, controlled, multicenter clinical trial to evaluate the efficacy and safety of oral sitafloxacin versus moxifloxacin in adult patients with community-acquired pneumonia.

OBJECTIVES: To evaluate the efficacy and safety of oral sitafloxacin versus oral moxifloxacin in the treatment of Chinese adults with community-acquired pneumonia (CAP). PATIENTS AND METHODS: This is a multicenter, randomized, open-label, positive-controlled clinical trial (chinadrugtrials.org.cn identifier: CTR20130046). CAP patients received sitafloxacin tablets 100 mg once daily (qd) or 100 mg twice daily (bid) to compare with moxifloxacin tablets 400 mg qd, for 7-10 days. The primary outcome was non-inferiority of sitafloxacin to moxifloxacin in clinical cure rate at test of cure (TOC) visit in per-protocol set (PPS). RESULTS: A total of 343 patients were randomized (sitafloxacin 100 mg qd, n = 117; sitafloxacin 100 mg bid, n = 116; moxifloxacin, n = 110), 291 patients were included in the PPS (sitafloxacin 100 mg qd, n = 96; sitafloxacin 100 mg bid, n = 94; moxifloxacin, n = 101). The clinical cure rate was 94.8% in the sitafloxacin 100 mg qd group, 96.8% in the sitafloxacin 100 mg bid group and 95.0% in the moxifloxacin group. At the TOC visit, the microbiological success rate was 97.0% (32/33) in the sitafloxacin 100 mg qd group, 97.1% (34/35) in the sitafloxacin 100 mg bid group and 94.9% (37/39) in the moxifloxacin group in the microbiological evaluable set (MES). The incidence of study-drug-related adverse events (AEs) was 23.3% (27/116) in the sitafloxacin 100 mg qd group, 29.8% (34/114) in the sitafloxacin 100 mg bid group and 28.2% (31/110) in the moxifloxacin group (p > .05). The common AEs related to study drug were dizziness, nausea, diarrhea, increased platelet count and alanine transaminase (ALT) elevation. All the AEs resolved completely after discontinuation of study drug. CONCLUSION: Sitafloxacin 100 mg qd or 100 mg bid for 7-10 days is not inferior to moxifloxacin 400 mg qd for 7-10 days in clinical efficacy for adult CAP patients. Sitafloxacin provides a safety profile comparable to moxifloxacin.

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.

A multicenter, prospective, observational study on montelukast monotherapy or montelukast-based combinations treating cough variant asthma.

BACKGROUND: Evidence of treatment against cough variant asthma (CVA) is insufficient for the clinical practice in China. We aimed at evaluating the real-world effectiveness of montelukast (MONT) alone or in combination with low-dose inhaled corticosteroids (ICS) and low-dose ICS plus long-acting beta-2-agonists (LABA) for Chinese CVA patients in a multicentre, prospective, cohort study. METHODS: Adult patients diagnosed with CVA defined as chronic cough >8 weeks with a positive bronchial provocation test and normal chest X-ray findings were enrolled at respiratory clinics. Study treatment followed routine clinical practice. The investigators initiated MONT by 10 mg/day alone or in combination with a low-dose ICS +/- LABA and followed up treatment outcomes for 4 weeks. The primary outcome measure was the change in cough score (CS) from baseline. RESULTS: The study enrolled 247 patients (MONT =146, MONT + ICS =38, MONT + ICS/LABA =63). In the primary analysis, the mean change (95% CI) in CS at the end of the study was -1.2 (-1.6, -0.9), -0.9 (-1.5, -0.4), and -1.3 (-1.7, -0.8) in the three groups, respectively. MONT monotherapy had a satisfactory rate of weekly asthma control at the end of the study (83.5%, 95% CI: 75.1%, 89.4%) in the per-protocol analysis. Rates of weekly asthma control were similar in two MONT-based combination regimens (83.9%, 81.4%). Short-acting beta-2-agonist (SABA) user (≥2 times per week) was 16.8% in the MONT group. CONCLUSIONS: The real-world effectiveness of MONT alone or in combination with ICS or ICS and LABA was acceptable for CVA short-term control.

Clinical characteristics of "re-positive" discharged COVID-19 pneumonia patients in Wuhan, China.

To analyze the clinical characteristics of re-positive discharged COVID-19 patients and find distinguishing markers. The demographic features, clinical symptoms, laboratory results, comorbidities, co-infections, treatments, illness severities and chest CT scan results of 267 patients were collected from 1st January to 15th February 2020. COVID-19 was diagnosed by RT-PCR. Clinical symptoms and nucleic acid test results were collected during the 14 days post-hospitalization quarantine. 30 out of 267 COVID-19 patients were detected re-positive during the post-hospitalization quarantine. Re-positive patients could not be distinguished by demographic features, clinical symptoms, laboratory results, comorbidities, co-infections, treatments, chest CT scan results or subsequent clinical symptoms. However, re-positive rate was found to be correlated to illness severity, according the Acute Physiology and Chronic Health Evaluation II (APACHE II) severity-of-disease classification system, and the confusion, urea, respiratory rate and blood pressure (CURB-65) score. Common clinical characteristics were not able to distinguish re-positive patients. However, severe and critical cases classified high according APACHE II and CURB-65 scores, were more likely to become re-positive after discharge.

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.

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.

MS-275 potentiates the effect of YM-155 in lung adenocarcinoma via survivin downregulation induced by miR-138 and miR-195.

BACKGROUND: YM-155 has been proven to be an efficient antitumor suppressor in non-small cell lung cancer (NSCLC) cells. However, the suppressive effect of YM-155 on the expression of survivin is not sufficient and has a short half-life. MS-275, a histone deacetylase inhibitor, has significant antitumor capacity with a relatively long half-life. Our study explored whether MS-275 could enhance the inhibitory effect of YM-155 on LUAD proliferation. METHODS: To investigate the synergistic effect of MS-275 and YM-155, we employed methyl thiazolyl tetrazolium and colony formation assays to access the inhibition effect of MS-275, YM-155, or a combination in A549 and HCC827 cell lines. We then detected the effect of MS-275 and YM-155 on the expression of survivin and pro-apoptotic proteins by Western blot and miR-138 or miR-195 expression by quantitative PCR. We also analyzed the methylation level of microRNAs (miRNAs) using methylation-sensitive quantitative PCR. Finally, we investigated the interaction between miRNAs and survivin by luciferase reporter assay. RESULTS: MS-275 facilitated an inhibitory effect of YM-155 on lung adenocarcinoma cell proliferation. MS-275 can upregulate the level of acetylated H3, promote the degradation of DNA methyltransferases, and inhibit the methylation of miR-138 and miR-195 genes to elevate the expression of miR-138 and miR-195. Moreover, miR-138 and miR-195 showed a synergistic effect with YM-155 by directly binding to the 3 untranslated region of survivin to attenuate its expression. CONCLUSION: For the first time, we report the synergistic effective of MS-275 and YM-155 and suggest a new direction for the future application of YM-155.