In chronic obstructive pulmonary disease, the senescence of type II alveolar epithelial cells is a key driver of disease progression, severely impacting lung function and structure. Lactate accumulation, a common feature of chronic hypoxic conditions such as COPD, is increasingly recognized for its role in modulating cellular functions via epigenetic mechanisms. This study aimed to investigate the specific effects of lactate-induced histone lactylation on AEC2 senescence and its contribution to COPD progression. Our experiments revealed a significant increase in histone lactylation levels in COPD models, with site-specific screening identifying histone H4 lysine 12 lactylation as a predominant modification. Using the Cleavage Under Targets and Tagmentation technique (CUT&Tag) sequencing, we demonstrated that H4K12la modulates the CD38-nicotinamide adenine dinucleotide (NAD⁺) signaling pathway, thereby promoting AEC2 senescence and exacerbating COPD progression. Further in vitro and in vivo analyses confirmed that elevated H4K12la expression was associated with increased CD38 levels and decreased NAD⁺ concentrations. To interrogate this pathway, we employed the p300/CBP inhibitor A485, which specifically inhibits H4K12la levels. This intervention significantly improved AEC2 senescence and reduced COPD-related pathology. Subsequently, we explored additional therapeutic strategies using the CD38 inhibitor 78c and the NAD+ precursor β - nicotinamide mononucleotide (NMN), both of which effectively reduced senescence markers and further ameliorated COPD symptoms. These findings highlight the critical role of lactate-induced histone lactylation, specifically H4K12la, in COPD pathogenesis. Targeting the H4K12la-CD38-NAD+ axis, with strategies such as p300/CBP inhibition, offers promising therapeutic avenues for managing the disease.

Background: COVID-19, caused by SARS-CoV-2, poses a significant threat to human health. Vaccines designed for T-cell epitopes play an important role in eliminating the virus. However, T cell epitope screening often requires the use of a large number of peripheral blood mononuclear cells (PBMCs) from infected or convalescent patients, and if MHC humanized mice can be used for epitope screening, they will not have to wait for enough PBMCs to be available to screen for epitopes, thus buying time for epitope confirmation and vaccine design. Methods: In this study, we used SARS-CoV-2 BA.5 to infect HLA-A11/DR1, C57BL/6, hACE2 mice, and detected body weight changes, viral load, and pathological changes after infection. Fourteen days after the HLA-A11/DR1 and C57BL/6 mice were immunized against inactivated viruses, IgG antibodies were detected in mouse serum using ELISA, and IFN-γ produced by peptide stimulation of splenocytes was detected by ELISpot. Results: There is no obvious pathogenic phenotype of SARS-CoV-2 infection in HLA-A11/DR1 mice. Specific IgG antibodies were detected in serum after immunization of inactivated virus in both HLA-A11/DR1 and C57BL/6 mice, but specific IFN-γ was detected in splenocytes of HLA-A11/DR1 mice. Conclusions: Although HLA-A11/DR1 mice are unable to replicate the virus effectively in vivo, they are able to generate cellular immune responses after immunization inactivated viruses. Therefore, it can be used as a tool to substitute for human PBMCs in epitope screening, thus shortening the timeliness of T cell epitope screening and obtaining the immunogenicity information of new epitopes in a timely manner.

OBJECTIVE:This study aimed to investigate the reasons behind the lower survival rates in male lung cancer patients than in female lung cancer patients. METHODS:Through various techniques, such as Argonaute immunoprecipitation, luciferase assays, and ChIP, this study confirmed the positive effects of androgen receptor (AR) on lung cancer cell invasion across different in vitro cell lines and in vivo mouse models. RESULTS:The findings suggest that AR enhanced the invasion of lung cancer cells by modifying EPHB2 signals at the protein expression level, which in turn required changes in miRNA-23a-3p. Restoring miRNA-23a-3p could counteract the intensified invasion of lung cancer cells mediated by AR. CONCLUSION:This study revealed that AR may facilitate the lung cancer matastasis by modulating miRNA-23a-3p/EPHB2 signaling and that targeting this signaling pathway could provide new approaches to inhibit lung cancer metastasis.

Objective:To explore the effect of different power microwave irradiation on bleomycin（BLM）-induced pulmonary fibrosis in rats.Method:The rat model of pulmonary fibrosis was established by tracheal injection of 5 mg/kg bleomycin.The rats were randomly divided into 4 groups:the normal control group,the model group,the 10min low power irradiation group,the 20min high power irradiation group.At 7d,14d and 28d after modeling,two microwave irradiation groups received microwave irradiation with different power,while the normal control group and the model group did not receive any irradiation.The pathological changes and the expression levels of fibrosis-related molecules（α-SMA,COL1a1） were detected by HE,Masson and IHC of lung tissues.The mRNA expression levels of inflammation-related molecules in lung tissues of rats were detected by q T-PCR.The metabolism of lung tissues was detected by F18-FDG PET-CT.Result:（1）The results of histopathological staining and immunohistochemistry showed that with the progress of the disease,the lung tissues of model group mainly exhibited enhanced and then stable alveolitis and enhanced fibrotic lesions.At 28 days after model establishment,low power microwave irradiation could significantly improve alveolitis and pulmonary fibrosis（alveolitis score P=0.0078,pulmonary fibrosis score P=0.0248,α-SMA P＜0.0001,COL1a1 P=0.0449）,and the expression of α-SMA was down-regulated in high power microwave irradiation group（P＜0.0001）.Microwave irradiation with different power showed no different effect on the pulmonary metabolism.（2）qRT-PCR results showed that the m RNA expressions of inflammatory factors in the lung tissues of the model group were increased at 28 days after modeling（P＜0.05）.Microwave irradiation could reduce the expression levels of inflammatory factors in lung tissue of rats with pulmonary fibrosis（the low-power group IL-1β P=0.0022,IL-6 P=0.0221,TNF-α P=0.0199,the high-power group IL-1β P=0.0276,IL-13 P=0.0276）.Microwave irradiation with different power showed no statistical difference.（3）PET-CT results showed that compared with the normal control group,the metabolic activity of lung tissue in the model group was enhanced 28 days after modeling（P=0.0485）.Microwave irradiation could enhance the metabolic capacity of lung tissue in a power-dependent manner（the high-power group P=0.0357）.Microwave irradiation with different power has no different effect on the metabolic ability of lung tissue.Conclusion:Microwave irradiation（low-power 90V/m,high-power 250V/m） may exert anti-inflammatory and anti-fibrosis effects by regulating the expression of inflammatory factors and fibrosis-related factors at 28d after modeling.

The transmembrane (TMEM) protein family is constituted by a large number of proteins that span the lipid bilayer. Dysregulation of TMEM protein genes widely occurs and is associated with clinical outcomes of patients with multiple tumors. Nonetheless, the significance of TMEM genes in the prognosis prediction of patients with osteosarcoma remains largely unclear. Here, we comprehensively analyzed TMEM protein family genes in osteosarcoma using public resources and bioinformatics methods. Prognosis-related TMEM protein family genes were identified by the univariate Cox regression analysis and were utilized to construct a signature based on six TMEM protein family genes (TMEM120B, TMEM147, TMEM9B, TMEM8A, TMEM59, and TMEM39B) in osteosarcoma. The prognostic signature stratified patients into high- and low-risk groups, and validation in the internal and external cohorts confirmed the risk stratification ability of the signature. Functional enrichment analyses of differentially expressed genes between high- and low-risk groups connected immunity with the prognostic signature. Moreover, we found that M2 and M0 macrophages were the most abundant infiltrated immune cell types in the immune microenvironment, and samples of the high-risk group showed a decreased proportion of M2 macrophages. Single-sample gene set enrichment analysis revealed that the scores of neutrophils and Treg were markedly lower in the high-risk group than these in the low-risk group in The Cancer Genome Atlas and GSE16091 cohorts. As for the related immune functions, APC co-inhibition and cytolytic activity exhibited fewer active levels in the high-risk group than that in the low-risk group in both cohorts. Of the six TMEM genes, the expression of TMEM9B was lower in the high-risk group than in the low-risk group and was positively associated with the overall survival of osteosarcoma patients. In conclusion, our TMEM protein family gene-based signature is a novel and clinically useful prognostic biomarker for osteosarcoma patients, and TMEM9B might be a potential therapeutic target in osteosarcoma.

目的 观察沉默lncRNA MEG3对慢性阻塞性肺疾病(COPD)小鼠肺功能的改善作用,并探讨其机制是否与调控白细胞介素1β(IL-1β)有关.方法 将32只野生型C57BL/6J小鼠随机分成control组、COPD组、COPD+NC组、COPD+siMEG3组,每组8只;除control组小鼠外,均采用香烟烟雾烟熏的方法建立COPD模型,COPD+NC组、COPD+siMEG3组同时尾静脉注射siRNA-Lipofectamine、NC-Lipofectamine复合体2.5 mg/kg,control组、COPD组注射等量生理盐水,1次/周,共注射12次.ASPER数据库及染色质免疫共沉淀实验证实lncRNA MEG3与IL-1β启动子区域存在结合位点,二者存在靶控关系.比较各组小鼠肺组织病理改变、氧合指数及肺湿重/干重,肺组织及BALF中的lncRNA MEG3及IL-1βmRNA、蛋白表达.结果 control组小鼠肺组织结构正常;COPD组及COPD+NC组小鼠肺泡结构紊乱,部分肺泡可见不规则扩大,肺泡、小气道及肺血管可见大量炎症细胞浸润;COPD+siMEG3组小鼠肺泡结构较COPD组及COPD+NC组完整,肺泡、小气道和肺血管少量炎症细胞浸润,支气管平滑肌层及管壁结构偶见异常.与control组和COPD+siMEG3组比较,COPD组、COPD+NC组肺湿重/干重均升高,氧合指数均降低(P均<0.05).各组小鼠BALF中均未检测到lncRNA MEG3表达.与control组、COPD+siMEG3组比较,COPD组及COPD+NC组肺组织lncRNA MEG3表达均升高且肺组织、BALF中IL-1βmRNA、蛋白均升高(P均<0.05).结论 沉默lncRNA MEG3可通过降低IL-1β表达而减轻COPD小鼠的肺损伤,从而发挥肺保护作用.

Vasculogenic mimicry (VM) has been reported as an alternative channel to increase tumor nutrient supplies and accelerate tumor progression, and is associated with poor survival prognosis in multiple cancers, including renal cell carcinoma (RCC). The currently used anti-angiogenic treatment for metastatic RCC, sunitinib, a tyrosine kinase inhibitor (TKI), has been reported to induce VM formation. Previously we identified that the estrogen receptor β (ERβ) functions as an oncogenic factor to promote RCC progression, supported by the analytic results from The Cancer Genome Atlas (TCGA) database. We have also found evidence that sunitinib induces RCC VM formation by up-regulating ERβ expression. In this study, we further demonstrated that treatment with sunitinib, as well as axitinib, another TKI, could induce ERβ expression in RCC cell lines. Clinical clear cell RCC (ccRCC) patients with higher ERβ expression are more likely to be found VE-cadherin positive and VM positive. Mechanism dissection showed that TKI- induced ERβ transcriptionally up-regulates the circular RNA of DGKD (circDGKD, hsa_circ_0058763), which enhances VE-cadherin expression by sponging the microRNA miR-125-5p family. Targeting circDGKD intercepts sunitinib-pretreatment-induced RCC VM formation, reduces metastases and improves survival in an experimental orthotopic animal model. Targeting ERβ/circDGKD signals may improve the TKI efficacy and provide novel combination therapies for metastatic RCC.

Background: The epidemic of COVID-19 presents a special threat to older adults. However, information on kidney damage in older patients with COVID-19 is limited. Acute kidney injury (AKI) is common in hospitalized adults and associated with poor prognosis. We sought to explore the association between AKI and mortality in older patients with COVID-19. Methods: We conducted a retrospective, observational cohort study in a large tertiary care university hospital in Wuhan, China. All consecutive inpatients older than 65 years with COVID-19 were enrolled in this cohort. Demographic data, laboratory values, comorbidities, treatments, and clinical outcomes were all collected. Data were compared between patients with AKI and without AKI. The association between AKI and mortality was analyzed. Results: Of 1764 in-hospital patients, 882 older adult cases were included in this cohort. The median age was 71 years (interquartile range: 68-77), 440 (49.9%) were men. The most presented comorbidity was cardiovascular diseases (58.2%), followed by diabetes (31.4%). Of 882 older patients, 115 (13%) developed AKI and 128 (14.5%) died. Patients with AKI had higher mortality than those without AKI (68 [59.1%] vs 60 [7.8%]; p < .001). Multivariable Cox regression analysis showed that increasing odds of in-hospital mortality are associated with higher interleukin-6 on admission, myocardial injury, and AKI. Conclusions: Acute kidney injury is not an uncommon complication in older patients with COVID-19 but is associated with a high risk of death. Physicians should be aware of the risk of AKI in older patients with COVID-19.

Objective:To analyze the composition and functional characteristics of the intestinal microflora in novel coronavirus pneumonia patients with arterial stiffness, in order to provide empirical evidence for rational use of intestinal microecological modulators.Methods:Patients with novel coronavirus pneumonia admitted to our hospital between April 5 and April 19, 2020 were enrolled as research subjects.They were divided into the stiffness group and the control group according to the results of arterial stiffness.Stool samples were collected within 7 days of admission.Intestinal flora DNA was analyzed and entered into a database, shotgun metagenomic sequencing was performed, and bioinformatics analysis was conducted based on sequencing results.Results:A total of 16 patients with novel coronavirus pneumonia were included in this study, including 7 in the stiffness group and 9 in the control group.Brachial-ankle pulse wave velocity and blood pressure were higher in the stiffness group than in the control group( P<0.05). Beta diversity analysis at the phylum level showed that there were significant differences in the composition of the intestinal flora between the two groups( P<0.05). Patients with arterial stiffness had a lower relative abundance than the controls in fecal Holdemanella, Mitsuokella, Deinococcus, Lachnospira, Turicibacter, Butyrivibrio, Sporomusa, and Halanaerobium, species associated with the production of short-chain fatty acids(SCFAs), regulation of energy metabolism, anti-radiation, anti-oxidative stress and anti-inflammatory effects.The Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis showed that the intestinal flora in the control group was mainly involved in the pathways of lipopolysaccharide biosynthesis, metabolism of SCFA and other amino acids, and membrane transport, while the intestinal flora in the stiffness group was mostly concerned with the pathways of amino acid metabolism and DNA damage repair. Conclusions:The use of microbial agents capable of increasing short-chain fatty acids in patients with novel caronavirus infection may contribute to the restoration of intestinal flora homeostasis.

Background: Cigarette smoke exposure (CSE) is a major cause of chronic obstructive pulmonary disease (COPD). The smoke disrupts cell-cell adhesion by inducing epithelial barrier damage to the tight junction (TJ) proteins. Even though the inflammatory mechanism of chemokine (C-C motif) ligand 3 (CCL3) in COPD has gained increasing attention in the research community, however, the underlying signaling pathway, remains unknown. Objectives: To identify the relationship of CCL3 in the pathogenesis of tight junction impairment in COPD and the pathway through which CSE causes damage to TJ in COPD via CCL3, both in vivo and in vitro . Methods: We screened the inflammatory factors in the peripheral blood mononuclear cells (PBMCs) from healthy controls and patients at each GOLD 1-4 stage of chronic obstructive pulmonary disease. RT-PCR, western blot, and ELISA were used to detect the levels of CCL3, ZO-1, and occludin after Cigarette smoke exposure. Immunofluorescence was applied to examine the impairment of the TJs in 16-HBE and A549 cells. The reverse assay was used to detect the effect of a CCR5 antagonist (DAPTA) in COPD. In the CSE-induced COPD mouse model, H&E staining and lung function tests were used to evaluate the pathological and physical states in each group. Immunofluorescence was used to assess the impairment of TJs in each group. ELISA and RT-PCR were used to examine the mRNA or protein expression of CCL3 or miR-4456 in each group. Results: The in vivo and in vitro results showed that CCL3 expression was increased in COPD compared with healthy controls. CCL3 caused significant injury to TJs through its C-C chemokine receptor type 5 (CCR5), while miR-4456 could suppress the effect of CCL3 on TJs by binding to the 3′-UTR of CCL3. Conclusion: miR-4456/CCL3/CCR5 pathway may be a potential target pathway for the treatment of COPD.

Objective Cardiac hypertrophy is an adaptive reaction of the heart against cardiac overloading, but continuous cardiac hypertrophy can lead to cardiac remodeling and heart failure. Cardiac hypertrophy is mostly considered reversible, and recent studies have indicated that decorin not only prevents cardiac fibrosis associated with hypertension, but also achieves therapeutic effects by blocking fibrosis-related signaling pathways. However, the mechanism of action of decorin remains unknown and unconfirmed. Methods We determined the degree of myocardial hypertrophy by measuring the ratios of the heart weight/body weight and left ventricular weight/body weight, histological analysis and immunohistochemistry. Western blotting was performed to detect the expression levels of CaMKII, p-CaMKII and MEF-2 in the heart. Results Our results confirmed that decorin can regulate the CaMKII/MEF-2 signaling pathway, with inhibition thereof being similar to that of decorin in reducing cardiac hypertrophy. Conclusion Taken together, the results of the present study showed that decorin induced cardiac hypertrophy by regulating the CaMKII/MEF-2 signaling pathway in vivo, revealing a new therapeutic approach for the prevention of cardiac hypertrophy.

The population is commonly susceptible to the 2019 novel coronavirus(2019-nCoV), especially the elderly with comorbidities.Elderly patients infected with 2019-nCoV tend to have higher rates of severe illnesses and mortality.Immunoaging is an important cause of severe novel coronavirus pneumonia(NCP)in the elderly.Due to the combination of underlying diseases, elderly patients may exhibit atypical manifestations in clinical symptoms, supplementary examinations and pulmonary imaging, deserving particular attention.The general condition of the elderly should be considered during diagnosis and treatment.In addition to routine care and measures such as oxygen therapy, antiviral therapy and respiratory support, treatment of underlying disease, nutritional support, sputum expectoration, complication prevention and psychological support should also be considered for elderly patients.Based on literature review and expert panel discussion, we drafted the Key Points for the Prevention and Treatment of the Novel Coronavirus Pneumonia in the elderly, aiming to provide help with the prevention and treatment of NCP and the reduction of harm to the elderly population.

COVID-19 patients can recover with a median SARS-CoV-2 clearance of 20 days post initial symptoms (PIS). However, we observed some COVID-19 patients with existing SARS-CoV-2 for more than 50 days PIS. This study aimed to investigate the cause of viral clearance delay and the infectivity in these patients. Demographic data and clinical characteristics of 22 long-term COVID-19 patients were collected. The median age of the studied cohort was 59.83 ± 12.94 years. All patients were clinically cured after long-term SARS-CoV-2 infection ranging from 53 to 112 days PIS. Peripheral lymphocytes counts were normal. The ratios of interferon gamma (IFN-γ)-secreting cells to total CD4+ and CD8+ cells were normal as 24.68% ± 9.60% and 66.41% ± 14.87% respectively. However, the number of IFN-γ-secreting NK cells diminished (58.03% ± 11.78%). All patients presented detectable IgG, which positively correlated with mild neutralizing activity (Mean value neutralisation antibodies titers = 157.2, P = 0.05). No SARS-CoV-2 virus was isolated in Vero E6 cells inoculated with nasopharyngeal swab samples from all patients 50 days PIS, and the cytopathic effect was lacking. But one sample was positive for SARS-CoV-2 nucleic acid test in cell supernatants after two passages. Genome sequencing revealed that only three synonymous variants were identified in spike protein coding regions. In conclusion, decreased IFN-γ production by NK cells and low neutralizing antibodies might favor SARS-CoV-2 long-term existence. Further, low viral load and weak viral pathogenicity were observed in COVID-19 patients with long-term SARS-CoV-2 infection.

BACKGROUND:A novel coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causing the pandemic of coronavirus disease 2019 (COVID-19), may attack testes by angiotensin-converting enzyme 2.OBJECTIVE:To assess whether SARS-CoV-2 infection can affect sex-related hormones and testicular function in recovering patients.MATERIALS AND METHODS:The patients were separately classified according to the duration of viral shedding (long-term positive vs normal-term group, with the former cases having a duration > 50 days) and disease severity (moderate vs severe group). Differences in sex-related hormone levels were compared between groups and linear regression analysis was used to compare the associations of testosterone (T) and estradiol with various clinical and laboratory factors.RESULTS:A total of 39 COVID-19-infected patients were included in this study. The mean T level was in the normal reference range while the mean estradiol level was above the normal limit. There were no significant differences between the long-term positive and normal-term groups in T (P = .964), follicle-stimulating hormone (FSH; P = .694), luteinizing hormone (LH; P = .171), prolactin (PRL; P = .836), or T/LH (P = .512). However, estradiol was higher in the normal-term group than the long-term positive group (P < .001). Moreover, there were also no significant differences between the moderate and severe groups in sex-related hormones, duration of viral shedding, or serum biochemical or inflammation indicators. Additionally, regression analyses showed that there were no associations between the T level and the clinical and laboratory factors, while estradiol was negatively associated with the duration of viral shedding.CONCLUSION:In males infected with SARS-CoV-2, most sex-related hormones (T, FSH and LH levels) remain within the normal reference ranges after recovery from COVID-19, and no significant associations were observed between T level and disease duration or severity. At present, there is insufficient evidence to show that SARS-CoV-2 causes hypogonadism and sterility, but the potential risk should not be ignored.

The population is commonly susceptible to the 2019 novel coronavirus (2019-nCoV), especially the elderly with comorbidities. Elderly patients infected with 2019-nCoV tend to have higher rates of severe illness and mortality. Immunosenescence is an important cause of severe novel coronavirus pneumonia (NCP) in the elderly. Due to the combination of underlying diseases, elderly patients may exhibit atypical manifestations in clinical symptoms, supplementary examinations, and pulmonary imaging, deserving particular attention. The general condition of the elderly should be considered during diagnosis and treatment. In addition to routine care and measures-such as oxygen therapy, antiviral therapy, and respiratory support-treatment of underlying disease, nutritional support, sputum expectoration complication prevention, and psychological support should also be considered for elderly patients. Based on a literature review and expert panel discussion, we drafted the "Recommendations for the Prevention and Treatment of the Novel Coronavirus Pneumonia in the elderly in China," aiming to provide help with the prevention and treatment of NCP and the reduction of harm to the elderly population.

The optogenetic neuron ablation approach enables noninvasive remote decoding of specific neuron function within a complex living organism in high spatiotemporal resolution. However, it suffers from shallow tissue penetration of visible light with low ablation efficiency. This study reports a upconversion nanoparticle (UCNP)-based multiplex proteins activation tool to ablate deep-tissue neurons for locomotion modulation. By optimizing the dopant contents and nanoarchitecure, over 300-fold enhancement of blue (450-470 nm) and red (590-610 nm) emissions from UCNPs is achieved upon 808 nm irradiation. Such emissions simultaneously activate mini singlet oxygen generator and Chrimson, leading to boosted near infrared (NIR) light-induced neuronal ablation efficiency due to the synergism between singlet oxygen generation and intracellular Ca2+ elevation. The loss of neurons severely inhibits reverse locomotion, revealing the instructive role of neurons in controlling motor activity. The deep penetrance NIR light makes the current system feasible for in vivo deep-tissue neuron elimination. The results not only provide a rapidly adoptable platform to efficient photoablate single- and multiple-cells, but also define the neural circuits underlying behavior, with potential for development of remote therapy in diseases.

Objective To explore the influence of tiotropium bromide powder inhalant or budesonide powder inhalant on sleep quality and lung function in patients with moderate and severe chronic obstructive pulmonary disease (COPD) in stable period. Methods Sixty-three patients with moderate and severe COPD in stable period were divided into 2 groups by random sortition method:tiotropium bromide group(31 cases,the patients inhaled tiotropium bromide powder inhalant 5 μg/time, 1 time/12 h) and budesonide group (32 cases, the patients inhaled budesonide powder inhalant 200 μg/time, 1 time/12 h). All patients were treated for 3 months. The lung function monitoring and polysomnography were detected before and after treatment. Results Seven patients withdrawn: 3 patients were in tiotropium bromide group,and 4 patients were in budesonide group.The forced expired volume in 1 second(FEV1),forced vital capacity(FVC),FEV1/FVC,peak expiratory flow(PEF)and forced expiratory flow from 25% to 75% (MMEF) after treatment in 2 group were significantly improved compared with those before treatment, and there were statistical differences (P<0.05). The FEV1, FVC and FEV1/FVC levels after treatment in tiotropium bromide group were significantly higher than those in budesonide group: (2.29 ± 0.43) L vs. (2.01 ± 0.42) L, (4.19 ± 0.26) L vs. (3.93 ± 0.23) L and (52.03 ± 10.45) % vs. (49.73 ± 10.21) %, and there were statistical differences (P<0.05). The percentages of S1 phase,S2 phase,rapid eye movement(REM)phase and activity apnea-hypopnea index (AHI)after treatment in 2 groups were significantly improved compared with those before treatment,and the indexes in tiotropium bromide group were significantly better than those in budesonide group:(29.99 ± 8.43)% vs. (26.91 ± 11.66)%, (48.99 ± 10.26)% vs. (45.45 ± 10.13)%, (14.83 ± 8.36)% vs. (13.33 ± 7.44)% and (8.70 ± 5.11) times/h vs. (11.72 ± 10.09) times/h, and there were statistical differences(P<0.05).Conclusions Tiotropium bromide has better effect in promoting the lung function and sleep quality compared with budesonide in patients with moderate and severe COPD in stable period.

Objective:To investigate the efficacy and safety of Tiotropium Respimat combined with inhaled corticosteroid (ICS)/long-acting β2-agonist (LABA) in elderly patients with chronic obstructive pulmonary disease (COPD).Methods:Fifty-four elderly COPD patients,who were classified as GOLD 3 or 4 and received ICS/LABA treatment,were randomized into LAMA + ICS/LABA group and ICS/LABA group.Patients in LAMA + ICS/LABA group were treated with Tiotropium Respimat plus ICS/LABA,and those in ICS/LABA group were given ICS/LABA.The annual declines of FEV1 and FVC,the improvements in COPD Assessment Test (CAT) score,the number of COPD exacerbations leading to hospitalization,and the incidence of major adverse cardiovascular events and drug-related adverse reactions were compared between the two groups after 12 months.Results:After 12 months,LAMA + ICS/LABA significantly reduced the declines of FEV1 and FVC versus ICS/LABA.There were significant improvements in CAT score in LAMA + ICS/LABA group versus ICS/LABA group.Fewer COPD exacerbations leading to hospitalization were observed in the LAMA + ICS/LABA group than in ICS/LABA group.There was no significant difference in the incidence of drug-related adverse reactions between the two groups and no major adverse cardiovascular events were observed.Conclusion:In elderly COPD patients,addition of Tiotropium Respimat to ICS/LABA demonstrated significant improvements in lung function and health status compared to ICS/LABA.

While estrogen receptor beta (ER beta) may impact the progression of non-small cell lung cancer (NSCLC), its linkage to alteration of the vasculogenic mimicry (VM) formation to influence the NSCLC cell invasion remains unclear. Here, we analyzed immunohistochemistry data from NSCLC tissues and found that ER beta-positive NSCLC female patients had worse survival outcomes than those of ER beta-negative NSCLC female patients. In vitro studies using multiple NSCLC cell lines also revealed that ER beta could increase the VM formation and cell invasion. Molecular mechanism dissection suggested that ER beta could increase the lncRNA-MALAT1 (MALAT1) expression via directly binding to the estrogen response elements (EREs) located on the promoter of MALAT1, which could then lead to (i) suppressing the miR145-5p and (ii) increasing the NEDD9 protein expression as miR145-5p can directly target the 3'-UTR of NEDD9-mRNA. A preclinical study using the in vivo mouse model further confirmed the in vitro cell lines data. Together, results from the above studies demonstrated that ER beta can promote NSCLC VM formation and cell invasion via altering the ER beta/MALAT1/miR145-5p/NEDD9 signaling. Targeting this newly identified signaling pathway with small molecules may help the development of novel therapies to better suppress the NSCLC metastasis.

miR-128 is expressed in various tumors, but its expression and function in gastric cancer have not been defined. Thus, the goal of this study was to characterize miR-128 in gastric cancer. We found first that miR-128 is down-regulated in gastric cancer cell lines and tissues, and this dysregulation is correlated with DNA methylation and the transcription factor SNAIL. Using prediction tools, western blotting, and luciferase reporter assays, we found that Bmi-1 was the direct target of miR-128. Additionally, overexpression of miR-128 inhibited gastric cancer cell migration, invasion, and proliferation by targeting Bmi-1 in vitro and in vivo. We also documented, with receiver operating characteristic curves and Kaplan-Meier survival analysis, that miR-128 and Bmi-1 may be useful markers for diagnosing and estimating the prognosis of gastric cancer patients. As the epithelial-to-mesenchymal transition is an important mechanism associated with cancer invasion and metastasis, we inferred that miR-128 could regulate this mechanism in gastric cancer. In fact, we found that miR-128 could reverse epithelial-to-mesenchymal transition induced by Bmi-1 via the PI3K/AKT pathway. Because SNAIL also acts as a mesenchymal marker, our findings identified a novel positive feedback loop in which the transcription factor SNAIL curbs the expression of miR-128, and then down-regulated miR-128 promotes the expression of Bmi-1; finally, overexpression of Bmi-1 drives the epithelial-to-mesenchymal transition process via the PI3K/AKT pathway, and the expression of SNAIL is up-regulated.