Biliary stents for active materials and surface modification: Recent advances and future perspectives.

Demand for biliary stents has expanded with the increasing incidence of biliary disease. The implantation of plastic or self-expandable metal stents can be an effective treatment for biliary strictures. However, these stents are nondegradable and prone to restenosis. Surgical removal or replacement of the nondegradable stents is necessary in cases of disease resolution or restenosis. To overcome these shortcomings, improvements were made to the materials and surfaces used for the stents. First, this paper reviews the advantages and limitations of nondegradable stents. Second, emphasis is placed on biodegradable polymer and biodegradable metal stents, along with functional coatings. This also encompasses tissue engineering & 3D-printed stents were highlighted. Finally, the future perspectives of biliary stents, including pro-epithelialization coatings, multifunctional coated stents, biodegradable shape memory stents, and 4D bioprinting, were discussed.

A randomized double-blind trial of TQB2450 with or without anlotinib in pretreated driver-negative non-small cell lung cancer.

OBJECTIVE: Immune monotherapy as second-line treatment confers only modest survival benefit on non-small cell lung cancer (NSCLC) patients with no mutated driver genes, necessitating combination treatment strategies. This phase Ib trial investigated the efficacy and safety of anti-PD-L1 antibody TQB2450 plus antiangiogenic drug anlotinib for NSCLC. MATERIALS AND METHODS: Pretreated stage IIIB or IV NSCLC patients with wild-type EGFR/ALK and minimally one measurable lesion were randomized 1:1:1 to receive TQB2450 1200 mg plus placebo, or TQB2450 1200 mg plus anlotinib 10 or 12 mg. The primary outcome was progression-free survival (PFS) and the secondary outcomes included objective response rate (ORR). RESULTS: Thirty-three patients received TQB2450 plus placebo and 34 patients each received TQB2450 plus anlotinib 10 mg and 12 mg. At the data cutoff, the median PFS was 8.7 months (95% CI 6.1-17.1) in the TQB2450 plus anlotinib group and 2.8 months (95% CI 1.4-4.7) in the TQB2450 only group. The ORR reached 30.9% (95% CI 20.2%-43.3%) in the TQB2450 plus anlotinib group and was 3.0% (95% CI 0.1%-15.8%) in the TQB2450 only group. In patients with PD-L1 ≥ 1%, the ORR was 50.0% (95% CI 33.4%-66.6%) for TQB2450 plus anlotinib and 5.3% (95% CI 0.1%-26.0%) for TQB2450 plus placebo. No new safety signals were observed. CONCLUSION: Anlotinib plus TQB2450 demonstrated promising antitumor activities in advanced NSCLC patients without EGFR and ALK alterations and the toxicities were overall manageable. The study findings support the continued development of TQB2450 plus anlotinib for advanced NSCLC patients without driver gene alterations.

Screening of potential microbial markers for lung cancer using metagenomic sequencing.

INTRODUCTION: Lung cancer is the most prevalent cancer with high mortality in China, and it is associated with the dysbiosis of the lung microbiome. This study attempted to screen for specific microorganisms as potential biomarkers for distinguishing benign lung disease from lung cancer. METHODS: Bronchoalveolar lavage fluid (BALF) sample was selected in the study instead of saliva to avoid contamination with oral microorganisms, and microbial taxonomic and functional differences in BALF samples from patients with lung cancer and those with those from patients with benign lung diseases were performed based on metagenomic next-generation sequencing, for the first time, so that microorganisms other than bacteria could be included. RESULTS: The results showed that the intrasample diversity of malignant samples was different from benign samples, and the microbial differences among malignant samples were smaller, with lower microbial diversity, significantly changed microbial abundance and metabolic functions. Metabolic function analysis revealed amino acid-related metabolism was more prevalent in benign samples, whereas carbohydrate-related metabolism was more prevalent in malignant samples. By LEfSe, Metastat and Random Forest analysis, we identified a series of important differential microorganisms. Importantly, the model combining five key genera plus one tumor marker (neuron-specific enolase) as indicators presented the optimal disease typing performance. CONCLUSION: Thus results suggest the value of these differential microorganisms enriched in tumors in mechanism research and may be potential new targets for lung cancer therapy. More importantly, the biomarkers identified in this study can be conducive to improve the clinical diagnosis of lung cancer and have good application prospects.

First Report of Athelia rolfsii Causing Stem Rot on Sunflower (Helianthus annuus L.) in Sichuan, China.

Sunflower (Helianthus annuus L.) is a major oilseed crop in the world, but recently it has become a popular ornamental flower in China (Kaya ET AL., 2012). Notably, stem rot was frequently observed on 30-day-old sunflower plants in Sichuan Province, P. R. China. In May 2021, 207 plants with stem rot and premature death were found among the investigated 1732 plants, with 11.95% incidence rate. Stem rot were mainly observed on the base stem of plants. Infected stems developed brown lesions that became slightly sunken and covered with white mycelial mats. With disease progress, the affected plants eventually wilted at early stage (Fig. 1A). For pathogen isolation, mycelia were harvested directly from diseased tissue and cultured on potato dextrose agar (PDA) at 25±2℃ in incubator without light. Eighteen fungal isolates with similar colony morphology were consistently isolated by purifying from different sampling areas. These isolates would form radial colonies with white aerial mycelia possessing branches and septa, and some could form clamp connection structure on PDA. Their average growth rate was 27.6 ± 0.09 mm per day (Fig. 1B & C). White granular sclerotia were abundantly produced on 6-day-old colonies. The sclerotia with a diameter of 1.18 ± 0.26 mm (n=348) gradually changed from white to light yellow and finally to brown with age (Fig. 1B). A representative isolate NCSF5.20-8 was identified accurately by multi-locus approach, and its genomic DNA was extracted for amplifying and sequencing the fragments of ITS, 18 S and TEF1-α according to previous description (Zhong et al., 2021). The nucleotide BLAST search of these sequences was nearly 100% identical to Athelia rolfsii (the teleomorph of Sclerotium rolfsii Sacc.) with accession number MN258360.1 (499/499 bp, 100%), AY665774.1 (1428/1428 bp, 100%), and JF267794.1 (489/490, 99%), respectively. The obtained sequences were deposited in GenBank with accession number OK635580.1, OM319631.1 and OK665849.1. Phylogenetic analysis based on simultaneously available ITS, 18S and TEF1-α sequences of Athelia genus indicated that NCSF5.20-8 could be clustered into the A. rolfsii clade with a support value of 100% (Fig. 2). Combining the above morphological characteristics and molecular identification, the isolate NCSF5.20-8 was finally confirmed as the identity of A. rolfsii (Mordue 1974; Zhong et al., 2021). In order to fulfil Koch's postulates and prove the pathogenicity of NCSF5.20-8 to sunflower, mycelial plugs were leaned on the base stem of healthy sunflower plants (cv. Guangwu muntain) with 45-day-old, while plants with same growth treated by PDA plug free of mycelium were used as control. All the inoculated plants were kept in a greenhouse at 25±2°C with 14 h photoperiod and 80% relative humidity. The experiments were conducted for triple biological repeats. Two days after inoculation, all the plants inoculated with NCSF5.20-8 had typical symptoms of stem rot, whereas, the control plants remained asymptomatic (Fig. 1D). Using above mentioned protocol, A. rolfsii was re-isolated only from the symptomatic stem of inoculated plants. To our knowledge, stem rot caused by A. rolfsii on sunflower has been reported in Italy and Turkey (Infantino et al., 1997; Cer & Morca, 2020), but it is the first report in China. For this pathogen has a wide host range with serious destructiveness (Punja, 1985), our research is beneficial to develop strategies to mitigate future losses of sunflower in China.

Circadian rhythm and clinical characteristics in patients with acute myocardial infarction combined with obstructive sleep apnea.

OBJECTIVE: The present study aimed to investigate the circadian rhythm and clinical characteristics of patients with acute myocardial infarction (AMI) combined with obstructive sleep apnea (OSA). METHODS: Patients with AMI combined with OSA were enrolled in the study, and those that met the inclusion criteria were divided into three time-period groups based on their sleep-wake rhythm (22:00-5:59, 6:00-13:59, and 14:00-21:59). The differences between the three groups of patients in sleep-monitoring data, blood routine, biochemical indicators, and coronary angiographic parameters were analyzed and compared. Count data were expressed as the number of cases, and the chi-square test was used for statistical analysis. Continuous data were expressed as mean ± standard deviation, and analysis of variance was used for the statistical analysis of these data. The characteristics of circadian rhythm and clinical features in patients with AMI combined with OSA were analyzed. RESULTS: Of the 148 patients, 90/148 (61%) had chest pain and 58/148 (39%) had non-chest pain symptoms. In the 22:00-05:59 group, there were 70/148 (47%) patients with AMI (of these, 46/70 [66%] had chest pain). In the 06:00-13:59 period group, there were 44/148 (30%) patients with AMI (of these, 26/44 [60%] had chest pain). In the 14:00-21:59 period group, there were 34/148 (23%) patients with AMI (of these, 17/34 [50%] had chest pain). There was no statistically significant difference in the apnea-hypopnea index (AHI) and SYNTAX score between patients in the 22:00-5:59 and 6:00-13:59 groups. However, the AHI and SYNTAX scores in the 22:00-5:59 and 6:00-13:59 groups were higher than those in the 14:00-21:59 group, and the differences were statistically significant. In patients in the 22:00-5:59 group, the levels of serum D-dimer (DD), hemoglobin (Hb), and oxygen desaturation index (ODI3) were higher, the sleep mean oxygen saturation (MeanSaO2 ) was lower and the percentage of nighttime spent with oxygen saturation of less than 90% (Tsat90 ) and less than 85% (Tsat85 ) was longer. CONCLUSION: The peak period for the onset of AMI in patients with OSA was 22:00-5:59, and the incidence of chest pain was high. During this period, patients had higher DD and Hb, higher ODI3, lower MeanSaO2 during sleep, and longer TSat90 and TSat85 . During the 22:00-5:59 and 6:00-13:59 periods, patients had higher AHI and a higher SYNTAX score.

G9a promotes inflammation in Streptococcus pneumoniae induced pneumonia mice by stimulating M1 macrophage polarization and H3K9me2 methylation in FOXP1 promoter region.

Background: Streptococcus pneumoniae has become a leading cause of pneumonia in recent years. Here, we investigated the mechanism of histone methylase G9a in Streptococcus pneumoniae-induced pneumonia (Spn). Methods: G9a expression in Spn mouse tissue was measured. G9a lentivirus interference vector was injected into Spn mice to evaluate the wet and dry weight of the right upper lobe and the total lung water content (TLW) and wet/dry ratio (W/D). The number of neutrophils, macrophages, and lymphocytes in bronchoalveolar lavage fluid (BALF) was detected, and the levels of interleukin-1ß (IL-1ß), IL-6, tumor necrosis factor-α (TNF-α), and IL-10 in BALF were assessed. The expressions of M1 and M2 macrophage markers were also detected. The enrichment of histone 3 lysine 9 dimethylation (H3K9me2) in the Forkhead Box P1 (FOXP1) promoter was detected by chromatin immunoprecipitation (ChIP) assay, and the transcription level of FOXP1 was detected. Mouse macrophage RAW264.7 was induced by lipopolysaccharide (LPS) following G9a interference. Results: G9a in the lung tissue of Spn mice was increased. After G9a knockdown, the mouse weight increased, the infiltration of inflammatory cells was decreased, levels of pro-inflammatory cytokines in BALF were decreased, CD86 and inducible nitric oxide synthase (iNOS) were decreased, and CD206 and arginase-1 (Arg-1) were elevated. In LPS-induced RAW264.7, G9a inhibited macrophage polarization to M1 and promoted macrophage polarization to M2. G9a promoted H3K9me2 methylation in the FOXP1 promoter region and inhibited its transcription, while FOXP1 downregulation reversed the inhibition of G9a knockdown on macrophage polarization to M1 and the inflammatory effect on Spn mice. Conclusions: G9a promotes M1 polarization of macrophages by promoting H3K9me2 methylation in the FOXP1 promoter region, promoting an inflammatory response in Spn mice.

Stimulation of both inspiratory and expiratory muscles versus diaphragm-only paradigm for rehabilitation in severe chronic obstructive pulmonary disease patients: a randomized controlled pilot study.

BACKGROUND: Chronic obstructive pulmonary disease (COPD), a progressive lung disease, might improve with neuromuscular electrical stimulation. No trials on inspiratory plus expiratory neuromuscular electrical stimulation have been conducted yet. AIM: The aim of this study was to evaluate the safety and effectiveness of inspiratory plus expiratory neuromuscular electrical stimulation in subjects with severe COPD. DESIGN: This was a multicenter, prospective, randomized controlled trial. SETTING: The subjects were outpatients enrolled from Beijing Chao-Yang Hospital affiliated with Capital Medical University, Tianjin Chest Hospital, and the First Hospital of Hebei Medical University. POPULATION: Subjects had stable COPD with severe respiratory impairment. METHODS: Using a computer statistical software, 120 stable subjects were randomly allocated (1:1) to receive inspiratory plus expiratory neuromuscular electrical stimulation (study group) and diaphragm pacing (control group). Demographic and clinical data were collected before, and after 2, and 4 weeks of the trial. The intention-to-treat analysis was conducted. The primary outcome was to analyze the changes in functional exercise capacity, estimated as six-minute walk distance (6MWD), following electrical stimulation for 4 weeks. The secondary outcomes were changes in modified Medical Research Council score, forced expiratory volume in 1 second (FEV1), FEV1% predicted, and FEV1 ratio forced vital capacity (FEV1/FVC) following electrical stimulation for 4 weeks. RESULTS: The change in 6MWD was greater in the study group (65.53±39.45 m) than in the control group (26.66±32.65 m). The mean between-group difference at the fourth week was 29.07 m (95% confidence interval, 16.098-42.035; P<0.001). There were no significant between-group differences in the secondary outcomes after 4 weeks of electrical stimulation. For GOLD-4 COPD subjects, FEV1 and FEV1/FVC improved in the study group (P<0.05). No electrical stimulation-related serious adverse events were observed in either group. CONCLUSIONS: 6MWD were increased significantly, without adverse events, after four weeks of treatment of inspiratory plus expiratory neuromuscular electrical stimulation in stable patients with severe COPD, suggesting that this protocol benefits COPD rehabilitation. CLINICAL REHABILITATION IMPACT: The results of this study suggest that the simultaneous use of inspiratory plus expiratory neuromuscular electrical stimulation as an adjunct therapy may improve the functional exercise capacity of severe stable COPD subjects.

Catechin regulates miR-182/GGPPS1 signaling pathway and inhibits LPS-induced acute lung injury in mice.

AIM: Acute lung injury (ALI) and resultant acute respiratory distress syndrome (ARDS) are detrimental inflammatory disease associated with high rates of morbidity and mortality due to a lack of effective treatment options. Previous study has demonstrated that an inhibition of geranylgeranyl pyrophosphate synthase large subunit 1 (GGPPS1) show a protective effect against ALI. METHOD: In this study, by using connective map (CMAP), we identified catechin as a potential drug to exhibit similar effects to inhibit GGPPS1. Furthermore, we detected the protective effect of catechin on lipopolysaccharide (LPS)-induced ALI and delineated the underlying mechanism. RESULTS: We found that catechin effectively ameliorated LPS-induced lung inflammation and alleviated the release of cytokines into alveolar space. Notably, miR-182/GGPPS1 signaling pathway was reactivated upon catechin administration, which was essential for the catechin-induced protective effect against ALI. CONCLUSION: catechin regulates miR-182/GGPPS1 signaling pathway and efficaciously ameliorates LPS-induced acute lung injury in mice model, which provided a promising therapeutic strategy in ALI and ARDS.

Investigation of differentially expressed gene profile for cisplatin-treated lung cancer patients.

The purpose of the study was to establish a comprehensive differential gene profile for lung cancer patients treated with cisplatin compared with control patients without any chemotherapy drug treatment. The RNA sequencing data and miRNA sequencing data of 108 lung cancer patients treated with cisplatin only and 232 lung cancer patients treated without any chemotherapeutic drugs, were analyzed using differential expression, protein-protein interaction, and immune cell infiltration ratio analysis. Compared with control patients, the cisplatin-treated patients demonstrated 336 differentially expressed genes, which included 48 upregulated genes and 288 downregulated genes. Meanwhile, 12 differentially expressed miRNAs (DEMs), including 7 upregulated miRNAs and 5 downregulated miRNAs showed a differentially expressed pattern. With further instigation, five miRNAs (hsa-miR-548ah, hsa-miR-466, hsa-miR-552, hsa-miR-371a, and hsa-miR-4445) were suggested to be the key targets in the cisplatin-treated patients. At the same time, we also found a significant correlation between the cisplatin treatment and six immune checkpoints including programmed cell death ligand. This study helped us better understand the potential targets and underline molecular mechanisms for cisplatin treatment and provided references to eliminate existing side effects in the future.

Expression of Matrix Metalloproteinase-2, Matrix Metalloproteinase-9, Tissue Inhibitor of Metalloproteinase-1, and Changes in Alveolar Septa in Patients with Chronic Obstructive Pulmonary Disease.

BACKGROUND This study investigated the relationship between the pathological alteration of alveolar septa and (1) pulmonary function and (2) matrix metalloproteinase (MMP)-2, MMP-9, and tissue inhibitor matrix metalloproteinase 1 (TIMP-1) expression in chronic obstructive pulmonary disease (COPD). MATERIAL AND METHODS Sixty patients with pulmonary disease were divided into control (n=20) and COPD (n=40) groups. Postoperative lung tissue specimens were examined. Hematoxylin and eosin and elastin van Gieson staining detected pathological alterations of pulmonary alveolar septa. Septa thickness was measured. MMP-2, MMP-9, and TIMP-1 expression levels were detected by immunohistochemical staining. Correlations were determined by Pearson analysis. RESULTS Forced expiratory volume in 1 s (FEV1), forced vital capacity, FEV1 percent predicted (FEV1%pre), and diffusion capacity of carbon monoxide percent predicted (DLCO%pre) in COPD patients were significantly lower than in those of the control group (P<0.05). MMP-2, MMP-9, and TIMP-1 expression levels were significantly higher in the COPD group than in control, especially the severe group (P<0.05). Septa thickness was negatively correlated with FEV1%pre (r=-0.335; P<0.05) and positively correlated with MMP-2 and TIMP-1 expression (P<0.05). Proportion of collagenous fiber was negatively correlated with FEV1%pre and DLCO%pre (P<0.01), and positively correlated with MMP-2, MMP-9, and TIMP-1 expression (P<0.01). Proportion of elastic fibers was negatively correlated with collagenous fiber. CONCLUSIONS The pathological alteration of alveolar septa was correlated with pulmonary function and expression levels of MMP-2, MMP-9, and TIMP-1, which can play vital roles in COPD progression.

Impact of chronic obstructive pulmonary disease on mortality in community acquired pneumonia: a meta-analysis.

Background: The aim of the present study was to systematically review the exiting literature and to proceed a meta-analysis to determine the impact of chronic obstructive pulmonary disease (COPD) on mortality in patients with community acquired pneumonia. Materials & methods: Eligible studies were searched from PubMed, Cochrane Library and EMBASE. Odds ratios (ORs) with 95% CIs were used as effect estimates. Results: Twenty cohort studies were included. Analysis of unadjusted data revealed nonsignificant short- and long-term mortality associated with COPD. Analysis of adjusted 30-days mortality showed similarly no association between COPD and increased 30-days mortality (OR: 1.06, [0.68, 1.44]) but a positive association when COPD was confirmed spirometrically (OR: 1.84, [1.06, 2.62]). Conclusion: There is still no evidence to clear the impact of COPD on mortality in patients with community acquired pneumonia. More prospective studies with spirometrically-defined COPD and adequate adjustment for confounders are needed.

Effects of Qizhukangxian granules on idiopathic pulmonary fibrosis: a randomized, double blind, placebo-controlled and multicenter clinical pilot trial.

OBJECTIVE: To evaluate the effects of Qizhukangxian granules (QG) on idiopathic pulmonary fibrosis (IPF). METHODS: This is a randomized, double blind, placebo-controlled and multicenter clinical pilot trial. Six medical centers in Tianjin, China, participated in the study. A total of 120 IPF patients were enrolled and randomized into two groups, with 60 patients in each group. The treatment group was treated with QG, while the control group received a Qizhukangxian placebo. The pharmacological treatment lasted for 48 weeks from the enrollment date. The indexes of patients were recorded on the admission day and at the end of the 24th and 48th weeks. Data were analyzed to study the effects of QG; forced vital capacity, change in forced vital capacity and maximal 6-min walk test (6MWT) distance were the primary endpoints. Secondary endpoints were percentage of patients with episodes of acute exacerbation of IPF, pulmonary function, changes in pulse oxygen saturation during the 6MWT, dyspnea score, St. George's respiratory questionnaire score, arterial blood gas analyses and the total Traditional Chinese Medicine symptom pattern score. RESULTS: After 24 weeks of treatment, QG showed greater efficacy than the placebo in certain parameters, including the dyspnea score, Traditional Chinese Medicine symptom pattern score and some indicators in the St. George's respiratory questionnaire score. Analysis of the indexes obtained from all patients at the end of the 48th week showed that the therapeutic effects in the treatment group were significantly better than those in the control group because remarkable differences were observed in most of the primary and secondary endpoints between the two groups, except for the maximal distance of the 6MWT and arterial blood gas analyses. No adverse reaction was observed in either group during the 48-week trial treatment period. CONCLUSION: QG could effectively treat IPF patients by ameliorating pulmonary function, improving the quality of life and lowering the percentage of acute exacerbations.

The Value of Combined Radial Endobronchial Ultrasound-Guided Transbronchial Lung Biopsy and Metagenomic Next-Generation Sequencing for Peripheral Pulmonary Infectious Lesions.

Background: Metagenomic next-generation sequencing (mNGS) is a new technology that allows for unbiased detection of pathogens. However, there are few reports on mNGS of lung biopsy tissues for pulmonary infection diagnosis. In addition, radial endobronchial ultrasound (R-EBUS) is widely used to detect peripheral pulmonary lesions (PPLs), but it is rarely used in the diagnosis of peripheral lung infection. Objective: The present study aims to evaluate the combined application of R-EBUS-guided transbronchial lung biopsy (TBLB) and mNGS for the diagnosis of peripheral pulmonary infectious lesions. Methods: From July 2018 to April 2019, 121 patients from Tianjin Medical University General Hospital diagnosed with PPLs and lung infection were enrolled in this prospective randomized study . Once the lesion was located, either TBLB or R-EBUS-guided-TBLB was performed in randomly selected patients, and mNGS was applied for pathogen detection in lung biopsy tissues. The results of mNGS were compared between the TBLB group and R-EBUS-guided TBLB group. In addition, the clinical characteristics and EBUS images from 61 patients receiving bronchoscopy for peripheral lung infectious detection were analyzed and compared with the results of mNGS. Results: The positivity rate of mNGS in R-EBUS-guided TBLB was (78.7%, 48/61) that was significantly higher than (60.0%, 36/60) in the TBLB group. Difference in the position of R-EBUS probe and image characteristics of peripheral lung infectious lesions affected the positivity rate of mNGS. Tissue collected by R-EBUS within the lesion produced higher positivity rate than samples collected adjacent to the lesion (P=0.030, odds ratio 17.742; 95% confidence interval, from 1.325 to 237.645). Anechoic areas and luminant areas of ultrasonic image characteristics were correlated with lower positivity rate of mNGS (respectively, P=0.019, odds ratio 17.878; 95% confidence interval, from 1.595 to 200.399; P=0.042, odds ratio 16.745; 95% confidence interval, from 1.106 to 253.479). Conclusions: R-EBUS-guided TBLB is a safe and effective technique in the diagnosis of peripheral lung infectious lesions. R-EBUS significantly facilitates the accurate insertion of bronchoscope into the lesions, which improves positivity rate of mNGS analysis in pathogen detection. The R-EBUS probe position within lesion produced a higher positivity rate of mNGS analysis. Nevertheless, the presence of anechoic and luminant areas on ultrasonic image was correlated with poor mNGS positivity rate.

One functional variant in the 3'-untranslated region of TLR4 is associated with the elevated risk of ventilator-associated pneumonia in the patients with chronic obstructive pulmonary disease.

The aim of this study was to identify the association polymorphism (rs11536889) in the 3'-untranslated region (3'-UTR) of Toll-like receptors 4 (TLR4) and the risk for ventilator-associated pneumonia (VAP). miRNA database online and luciferase assays were used to validate TLR4 as the target gene of miR-1236. Enzyme-linked immunosorbent assay analysis and western blot were used to analyze the level of TLR4 in different genotype groups. In the present study, miR-1236 was predicted to bind to the rs11536889 G allele rather than the rs11536889 C allele, which was further confirmed by the luciferase activity suppressed by a fragment of 3'-UTR containing the rs11536889 G allele induced by lipopolysaccharide (LPS) and interleukin-6 (IL-6). Bronchial epithelial cells isolated from participants genotyped as GG, GC, and CC, with no remarkable difference in TLR4 messenger RNA (mRNA) levels were observed among these genotype groups. After stimulating by LPS, a TLR4 ligand, the CC-genotyped cells expressed higher levels of IL-8, IL-6, and tumor necrosis factor alpha (TNF-α) on their surfaces than cells with the other genotypes. Finally, the western blot analysis results showed that the expression level of IL-8, IL-6, and TNF-α protein was much higher in the CC group than the GC and GG groups subsequent to stimulation by LPS, and the IL-8, IL-6, and TNF-α protein levels in the GC were grouped much lower compared with the GG group. These findings indicated the regulatory association of miR-1236 with TLR4 and the abnormal expression of TLR4 caused by the presence of rs11536889 in the 3'-UTR of mRNA, which interfere with its interaction with the miR-1236, contributing to the risk of VAP.

Assessment of a Domiciliary Integrated Pulmonary Rehabilitation Program for Patients with a History of Acute Exacerbation of Chronic Obstructive Pulmonary Disease: A Retrospective 12-Month Observational Study.

BACKGROUND Integrated pulmonary rehabilitation (PR) in chronic obstructive pulmonary disease (COPD) may prevent acute exacerbations of COPD (AECOPD). The aim of this study was to evaluate the effectiveness, before and 12 months after, the use of an integrated PR program in patients discharged from hospital for AECOPD. MATERIAL AND METHODS A retrospective observational clinical study included patients diagnosed with COPD who participated in a domiciliary integrated PR program that included a weekly phone interview supervised by a respiratory team. A six-minute walk test (6MWT), COPD assessment test (CAT), and the modified Medical Research Council scale (mMRC) were evaluated every three months. RESULTS Of the 303 eligible patients, 267 patients (88.1%), with a mean age of 64.9±8.7 years, a mean FEV1 percentage predicted of 48.8±12.9%, successfully completed the 12-month study program and achieved a significant improvement in their clinical performance with a significantly reduced frequency of episodes of EACOPD (3.1±1.7 vs. 2.0±1.4) (p<0.001), a significant reduction in emergency department visits (2.5±1.5 vs. 1.2±1.1) (p<0.001), and significantly reduced episodes of hospitalization (2.0±1.2 vs. 1.4±1.2) (p<0.001). Significant patient benefits were found during the 12-month study, on CAT, mMRC, and patient well-being when compared with the end of the study after 12 months (p<0.001). CONCLUSIONS A multidisciplinary integrated PR program maintained a significant clinical improvement, in patients with COPD by reducing episodes of AECOPD, CAT, mMRC, emergency hospital admissions, and improved patient well-being, for the duration of the program.

A new pulmonary rehabilitation maintenance strategy through home-visiting and phone contact in COPD.

BACKGROUND: The benefit of pulmonary rehabilitation (PR) for patients with COPD diminishes over time. We investigated a new strategy involving home-visit and phone contact and compared this to usual care in maintenance of PR benefits. METHODS: A total of 172 stable COPD patients receiving 8-week PR program were recruited for this prospective study. Patients were allocated into usual care group (UC) and PR maintenance group (PRMG) randomly. Patients in PRMG participated in maintenance strategy at home under supervision through home-visit and phone contact. The 6-minute walking test (6MWT), COPD assessment test (CAT), and modified Medical Research Council scale (mMRC) scores were evaluated every 3 months. RESULTS: Of the total, 151 patients completed 8-week PR program with satisfactory PR results (p<0.001), and 104 patients finished the follow-up. The clinical improvements in 6MWT, CAT, and mMRC scores were maintained (p<0.001) in PRMG. In comparison, the benefit of PR diminished gradually in UC. The differences in 6MWT, CAT, and mMRC scores between groups were observed 6, 9, and 6 months after PR, respectively (p<0.05). Total frequency of exacerbations in PRMG was lower than UC (p=0.021). CONCLUSION: Maintenance strategy involving home-visit and phone contact is superior to usual care to preserve PR benefits, and reduces the acute COPD exacerbation rate.

Pulmonary veins stenosis after catheter ablation of atrial fibrillation as the cause of haemoptysis: three cases and a literature review.

BACKGROUND: Haemoptysis is a common clinical symptom with a complicated aetiology. Patients usually visit pulmonologists initially and are misdiagnosed due to physician ignorance regarding the rare causes of haemoptysis. METHODS: We report three cases of haemoptysis due to pulmonary vein stenosis accompanied by catheter ablation for atrial fibrillation and review the related literature. RESULTS: The three patients presented haemoptysis and they all had the history of catheter ablation. They received kinds of non-invasive and invasive diagnostic and therapeutic procedures. Finally they were confirmed to have pulmonary vein stenosis by either pulmonary angiography or thorax computed tomography three-dimensional reconstructions. CONCLUSIONS: Haemoptysis could be caused by pulmonary vein stenosis secondary to catheter ablation for atrial fibrillation. Doctors should be aware of this rare aetiology.

Psychometric properties of the Anxiety Inventory for Respiratory Disease in patients with COPD in China.

BACKGROUND: Anxiety is a common comorbidity in patients with COPD in China, and it can significantly decrease patients' quality of life. Almost all anxiety measurements contain somatic items that can overlap with symptoms of COPD and side effects of medicines, which can lead to bias in measuring anxiety in patients with COPD. Therefore, a brief and disease-specific non-somatic anxiety measurement scale, the Anxiety Inventory for Respiratory Disease (AIR), which has been developed and validated in its English version, is needed for patients with COPD in China. METHODS: A two-center study was conducted in two tertiary hospitals in Tianjin, China. A total of 181 outpatients with COPD (mean age 67.21±8.10 years, 32.6% women), who met the inclusion and exclusion criteria, were enrolled in the study. Test-retest reliability was examined using intraclass correlation coefficients. The internal consistency was calculated by Cronbach's α. Content validity was examined using the Content Validity Index (CVI), scale-level CVI/universal agreement, and scale-level CVI/average agreement (S-CVI/Ave). Besides, convergent validity and construct validity were also examined. RESULTS: The AIR-C (AIR-Chinese version) scale had high test-retest reliability (intraclass correlation coefficient =0.904) and internal consistency (Cronbach's α=0.914); the content validity of the AIR-C scale was calculated by CVI, scale-level CVI/universal agreement, and S-CVI/Ave at values of 0.89-1, 0.90, and 0.98, respectively. Meanwhile, the AIR-C scale had good convergent validity, correlating with the Hospital Anxiety and Depression Scale-Anxiety (r=0.81, P<0.01), and there were significant correlations between the AIR-C and Clinical COPD Questionnaire (CCQ; r=0.44, P<0.01) and Activities of Daily Living Scale (ADLS; r=0.36, P<0.01). A two-factor model of general anxiety and panic symptoms in the AIR-C scale had the best fit according to Confirmatory Factor Analysis (CFA). CONCLUSION: The AIR-C scale had a good reliability and validity for patients with COPD and can be used as a user-friendly and valid tool for measuring anxiety symptoms among patients with COPD in China.

Lung Cancer Complicated With Asymptomatic Pulmonary Embolism: Clinical Analysis of 84 Patients.

BACKGROUND AND OBJECTIVE: Pulmonary embolism is potentially life-threatening in patients with lung cancer, but the clinical studies on patients with lung cancer having asymptomatic pulmonary embolism were barely reported. METHODS: Clinical data of patients with lung cancer were obtained from the Department of Respiratory and Critical Care Medicine of Tianjin Chest Hospital during July 2012 and June 2015 and were reviewed retrospectively. A total of 28 patients with lung cancer having pulmonary embolism (LP group) were enrolled, and another 56 cases with lung cancer alone (LC group) were enrolled as controls. RESULTS: Seventeen (60.7%) of 28 patients in the LP group developed adenocarcinoma, which was more frequent than that in the LC group ( P < .01); the LP group displayed lower counts of hemoglobin and albumin than the LC group ( P < .05); the counts of leukocyte (white blood cell) and d-dimer of patients in the LP group were also higher than those in the LC group ( P < .05). The high-incidence period of pulmonary embolism among 17 asymptomatic cases in the LP group was 3.6 months postdiagnosis (95% confidence interval, 3.2-4.0), showing a significant difference with that of other 11 patients with symptomatic pulmonary embolism, which was 10.5 months (95% confidence interval, 8.88-12.12; P < .01). Survival analysis displayed that median survival time of patients with asymptomatic pulmonary embolism was 7.2 months (95% confidence interval, 5.86-8.56), while that of symptomatic pulmonary embolism was 2.8 months (95% confidence interval, 2.48-3.12). Log-rank examination showed that survival time of asymptomatic pulmonary embolism group was statistically longer than that of symptomatic pulmonary embolism group. CONCLUSION: Lung adenocarcinoma, chemotherapy, hyperleukocytosis, and d-dimer increment were the risk factors for lung cancer combined with asymptomatic pulmonary embolism.

Effect of bufei granule on stable chronic obstructive pulmonary disease: a randomized, double blinded, placebo-controlled, and multicenter clinical study.

OBJECTIVE: To study the therapeutic effect Bufei granule, which is a traditional Chinese drug that can enhance the immune function of the lung, on patients with stable chronic obstructive pulmonary disease (COPD). METHODS: This is a randomized, double blinded, placebo-controlled, and multicenter clinical study. Three medical centers in Tianjin, China, participated in the trial. A total of 140 patients with stable COPD were enrolled and randomized into two groups, with 70 patients in each. The treatment group was treated with Bufei granule, while the control group received Bufei placebo. The pharmacological treatment lasted for 12 weeks from the date of enrollment. Then, the indexes of patients were observed. Data were analyzed to study the effect of Bufei granule, with the frequency of acute exacerbation as the primary outcome. Traditional Chinese Medicine syndromes, Modified British Medical Research Council dyspnea scale score, St. George's respiratory questionnaire scores, pulmonary function, and serum inflammatory marker levels [including interleukin-6 (IL-6), interleukin-8, tumor necrosis factor-alpha, and transformation growth factor-beta1] were the secondary outcomes. RESULTS: During the 12-week treatment, treatment and control groups had no adverse reactions. The analysis of the indexes obtained from all patients showed that the therapeutic effect in the treatment group was significantly better than that in the control group because most of the similar probabilities of primary and secondary outcomes were less than 0.05, except for the level of IL-6. CONCLUSION: Bufei granule can treat patients with stable COPD by lowering the frequency of acute exacerbation, improving the quality of life, and alleviating the severity of inflammation.