Bacterial interactome disturbance in chronic obstructive pulmonary disease clinical stability and exacerbations.

RATIONALE: Our understanding of airway dysbiosis in chronic obstructive pulmonary disease (COPD) remains incomplete, which may be improved by unraveling the complexity in microbial interactome. OBJECTIVES: To characterize reproducible features of airway bacterial interactome in COPD at clinical stability and during exacerbation, and evaluate their associations with disease phenotypes. METHODS: We performed weighted ensemble-based co-occurrence network analysis of 1742 sputum microbiomes from published and new microbiome datasets, comprising two case-control studies of stable COPD versus healthy control, two studies of COPD stability versus exacerbation, and one study with exacerbation-recovery time series data. RESULTS: Patients with COPD had reproducibly lower degree of negative bacterial interactions, i.e. total number of negative interactions as a proportion of total interactions, in their airway microbiome compared with healthy controls. Evaluation of the Haemophilus interactome showed that the antagonistic interaction networks of this established pathogen rather than its abundance consistently changed in COPD. Interactome dynamic analysis revealed reproducibly reduced antagonistic interactions but not diversity loss during COPD exacerbation, which recovered after treatment. In phenotypic analysis, unsupervised network clustering showed that loss of antagonistic interactions was associated with worse clinical symptoms (dyspnea), poorer lung function, exaggerated neutrophilic inflammation, and higher exacerbation risk. Furthermore, the frequent exacerbators (≥ 2 exacerbations per year) had significantly reduced antagonistic bacterial interactions while exhibiting subtle compositional changes in their airway microbiota. CONCLUSIONS: Bacterial interactome disturbance characterized by reduced antagonistic interactions, rather than change in pathogen abundance or diversity, is a reproducible feature of airway dysbiosis in COPD clinical stability and exacerbations, which suggests that we may target interactome rather than pathogen alone for disease treatment.

Risk factors of low-level viremia in chronic hepatitis B patients receiving Entecavir monotherapy: a retrospective cohort study.

BACKGROUND AND AIM: Low-level viremia (LLV), a special case of poor response to antiviral therapy, has become a focus of liver disease research; however, most studies have focused on poor response to antiviral therapy, and little attention has been paid to LLV. Therefore, this study aimed to investigate the factors influencing LLV in patients with chronic hepatitis B (CHB) receiving entecavir (ETV) monotherapy. METHODS: Clinical data of CHB patients receiving ETV treatment for at least 1 year at the outpatient department of the Affiliated Hospital of Xuzhou Medical University from November 2018 to June 2020 were collected. Patients were divided into LLV (180 cases) and sustained virological response (SVR) groups (337 cases) according to the hepatitis B virus (HBV) DNA load at the end of the observation period. Demographic features and laboratory markers were also examined. Univariate and multivariate logistic regression analyses were performed to examine factors influencing LLV in patients receiving long-term ETV monotherapy. RESULTS: Significant differences were noted between the LLV and SVR groups in terms of age, sex, presence or absence of cirrhosis, HBeAg positivity rate, baseline HBV DNA load, and baseline HBsAg level before treatment. Multivariate logistic regression analysis showed that baseline HBeAg status, HBV DNA load, and HBsAg quantification were pretreatment risk factors for LLV in long-term ETV antiviral therapy. CONCLUSIONS: CHB patients with a high HBV DNA load, high HBsAg quantification, and positive HBeAg results tend to have a high risk of LLV despite long-term ETV antiviral treatment and should be dynamically monitored.

Metagenomic next-generation sequencing in the diagnosis of neurocysticercosis: A case report.

BACKGROUND: The clinical symptoms and imaging manifestations of neurocysticercosis (NCC) are very different, and the difficulty and delay of clinical diagnoses may lead to an increase in mortality and disability. Rapid and accurate pathogen identification is important for the treatment of these patients. Metagenomic next-generation sequencing (mNGS) is a powerful tool to identify pathogens, especially in infections that are difficult to identify by conventional methods. CASE SUMMARY: A 43-year-old male patient was admitted due to a recurrent headache for a few months. Imaging examinations showed hydrocephalus and cystic lesions, which were considered to be a central nervous system infection, but no etiology was found by routine examination. mNGS of the cerebrospinal fluid revealed high Taenia solium reads, and the positive results of a cysticercosis antibody test confirmed the infection. Combined with the patient's clinical manifestations, the etiological evidence, and the imaging manifestation, the patient was finally diagnosed with NCC and he was prescribed dexamethasone, albendazole, neurotrophic drugs, and intracranial pressure reduction therapy. The headaches disappeared after anti-parasite treatment, and no associated symptoms recurred prior to the three- and six-month follow-up. CONCLUSION: As an accurate and sensitivity detection method, mNGS can be a reliable approach for the diagnosis of NCC.

[Progress of researches on anti-inflammatory mechanism of acupuncture underlying amelioration of chronic respiratory diseases].

In recent years, acupuncture has gained great progress in the treatment of chronic respiratory diseases (CRD), and the clinical effect is remarkable, but its underlying mechanisms are relatively complex, with the anti-inflammatory effect being the primary aspect. Based on the literature both at home and abroad, we found that the anti-inflammatory mechanism of acupuncture mainly involves chemokines, kinase-related pathways, helper T cells, epigenetic modification, autophagy, vagal-mediated cholinergic anti-inflammatory pathway, etc. The researches on some anti-inflammatory mechanisms are still in the initial stage, the relationship among various pathways, and the key factors affecting the effect of acupuncture, such as acupoint selection, stimulation intensity and needling depth, etc. warrant further exploration in the future.

Acupuncture for dyspnea and breathing physiology in chronic respiratory diseases: A protocol of a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Dyspnea is one of the most common symptoms of chronic respiratory disease (CRD) and is closely related to increased functional disability and mortality, resulting in substantial adverse outcomes on patients and imposing great social and economic burden. Although multiple clinical trials and systematic reviews have suggested that acupuncture could be effective in treating COPD and lung cancer, little is known about its effects on dyspnea relief in patients with CRD. The present study aimed to use a systematic review approach to evaluate the effectiveness and safety of acupuncture in the treatment of dyspnea in patients with CRD. METHODS: We will search the following 9 databases from inception to June 30, 2022, PubMed, Web of Science, EMBASE, Cochrane Central Register of Controlled Trials, Chinese National Knowledge Infrastructure, WANFANG Database, Chinses Scientific and Technological Periodical Database, and Chinese Biomedical Database, and the Cochrane Library Database. Clinical randomized controlled trials in English or Chinese that evaluate invasive acupuncture versus control group in treatment of CRD with dyspnea will be included. The primary outcome will be dyspnea scores, breathing physiological function, and the secondary outcomes include exercise tolerance by six-minute walk distance quality of life, quality of life and adverse events. Two reviewers will independently conduct study selection, data extraction and quality assessment. The Review Manager software will be used for meta-analysis. This protocol will be carried out in accordance with the PRISMA-P guidance. CONCLUSION: This systematic review and meta-analysis will provide the evidence of whether acupuncture is an effective and safe intervention for CRD with dyspnea. The results will be disseminated through peer-reviewed publication.

Signature based on RNA-binding protein-related genes for predicting prognosis and guiding therapy in non-small cell lung cancer.

Background: Studies have reported that RNA-binding proteins (RBPs) are dysregulated in multiple cancers and are correlated with the progression and prognosis of disease. However, the functions of RBPs in non-small cell lung cancer (NSCLC) remain unclear. The present study aimed to explore the function of RBPs in NSCLC and their prognostic and therapeutic value. Methods: The mRNA expression profiles, DNA methylation data, gene mutation data, copy number variation data, and corresponding clinical information on NSCLC were downloaded from The Cancer Genome Atlas, Gene Expression Omnibus, and the University of California Santa Cruz Xena databases. The differentially expressed RBPs were identified between tumor and control tissues, and the expression and prognostic value of these RBPs were systemically investigated by bioinformatics analysis. A quantitative polymerase chain reaction (qPCR) was performed to validate the dysregulated genes in the prognostic signature. Results: A prognostic RBP-related signature was successfully constructed based on eight RBPs represented as a risk score using least absolute shrinkage and selection operator (LASSO) regression analysis. The high-risk group had a worse overall survival (OS) probability than the low-risk group (p < 0.001) with 1-, 3-, and 5-year area under the receiver operator characteristic curve values of 0.671, 0.638, and 0.637, respectively. The risk score was associated with the stage of disease (p < 0.05) and was an independent prognostic factor for NSCLC when adjusted for age and UICC stage (p < 0.001, hazard ratio (HR): 1.888). The constructed nomogram showed a good predictive value. The P53, focal adhesion, and NOD-like receptor signaling pathways were the primary pathways in the high-risk group (adjusted p value <0.05). The high-risk group was correlated with increased immune infiltration (p < 0.05), upregulated relative expression levels of programmed cell death 1 (PD1) (p = 0.015), cytotoxic T-lymphocyte-associated protein 4 (CTLA4) (p = 0.042), higher gene mutation frequency, higher tumor mutational burden (p = 0.034), and better chemotherapy response (p < 0.001). The signature was successfully validated using the GSE26939, GSE31210, GSE30219, and GSE157009 datasets. Dysregulation of these genes in patients with NSCLC was confirmed using the qPCR in an independent cohort (p < 0.05). Conclusion: An RBP-related signature was successfully constructed to predict prognosis in NSCLC, functioning as a reference for individualized therapy, including immunotherapy and chemotherapy.

Diagnostic performance of mycological tests for invasive pulmonary aspergillosis in non-haematological patients: protocol for a systematic review and meta-analysis.

INTRODUCTION: Increasing numbers of patients with non-haematological diseases are infected with invasive pulmonary aspergillosis (IPA), with a high mortality reported which is mainly due to delayed diagnosis. The diagnostic capability of mycological tests for IPA including galactomannan test, (1,3)-ß-D-glucan test, lateral flow assay, lateral flow device and PCR for the non-haematological patients remains unknown. This protocol aims to conduct a systematic review and meta-analysis of the diagnostic performance of mycological tests to facilitate the early diagnosis and treatments of IPA in non-haematological diseases. METHODS AND ANALYSIS: Database including PubMed, CENTRAL and EMBASE will be searched from 2002 until the publication of results. Cohort or cross-sectional studies that assessing the diagnostic capability of mycological tests for IPA in patients with non-haematological diseases will be included. The true-positive, false-positive, true-negative and false-negative of each test will be extracted and pooled in bivariate random-effects model, by which the sensitivity and specificity will be calculated with 95% CI. The second outcomes will include positive (negative) likelihood ratio, area under the receiver operating characteristic curve and diagnostic OR will also be computed in the bivariate model. When applicable, subgroup analysis will be performed with several prespecified covariates to explore potential sources of heterogeneity. Factors that may impact the diagnostic effects of mycological tests will be examined by sensitivity analysis. The risk of bias will be appraised by the Quality Assessment tool for Diagnostic Accuracy Studies (QUADAS-2). ETHICS AND DISSEMINATION: This protocol is not involved with ethics approval, and the results will be peer-reviewed and disseminated on a recognised journal. PROSPERO REGISTRATION NUMBER: CRD42021241820.

[Research progress of neuroendocrine mechanism of acupuncture for dyspnea].

The paper reviewed the relevant studies on dyspnea treated with acupuncture over the past 20 years, as well as the underlying neuroendocrine mechanism from the perspective of central and peripheral vagus nerves, neurotransmitter, respiratory muscle function and anti-depression-anxiety function. It revealed that the central response area was regulated by acupuncture in treatment of dyspnea, which is similar to the area affected in acupuncture analgesia. Additionally, acupuncture generates its therapeutic effects on dyspnea through promoting the release of endogenous opioid peptides and the regulation of autonomic nerve, amygdale and hypothalamic-pituitary-adrenal axis.

Identification of Survival-Associated Gene Signature in Lung Cancer Coexisting With COPD.

Background: Chronic obstructive pulmonary disease (COPD) and lung cancer often coexist, which is associated with a worse prognosis. Thousands of biomarkers related to the survival of lung cancer have been investigated. However, those which can predict the survival of lung cancer coexisting with COPD are currently lacking. The present study aimed to identify novel gene signatures to predict the survival of patients with lung cancer coexisting COPD. Method: RNA-sequence data of lung cancer and control accompanying with matched clinical information were retrieved from the Cancer Genome Atlas (TCGA). Differently expressed genes (DEGs) associated with lung cancer coexisting COPD were screened. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were performed. Univariate and multivariate Cox regression analyses were applied to identify survival-associated DEGs and to construct survival-associated gene signature. Kaplan-Meier survival analysis and calibration plots of the nomogram were performed to test the predictive accuracy of the gene signature. qPCR was performed to validate the genes in the prognostic signature. Results: Sequence data from 70 patients with lung cancer coexisting COPD, 127 with lung cancer alone and 108 control tissues were included for analysis. A total of 2424 DEGs were identified when comparing lung cancer coexisting COPD with controls. The biological process was primarily associated with DNA-binding transcription activator activity, peptidase inhibitor activity, endopeptidase inhibitor activity, et al. KEGG pathways were mainly enriched in neuroactive ligand-receptor interaction, cell cycle, and Staphylococcus aureus infection. A survival-associated gene signature consisting of CEACAM5, RASAL1, CSTL1, CNGB1, and SLC4A3 was identified and represented as risk score. The high-risk score group had significantly worse survival than the low-risk score group (P < 0.001). Areas under receiver operating characteristic curves were 0.943, 0.773, 0.888 for predicting overall survival at 1-, 3-, and 5-year, respectively. The risk score was an independent predictor of survival, independent of clinical factors. High conformity of the actual survival and the nomogram-predicted probability of survival by applying the risk score. Upregulation of the five genes in patients with lung cancer coexisting COPD were confirmed by qPCR in an independent cohort. Conclusion: Our study constructed and validated a novel prognostic gene signature for predicting survival of patient with lung cancer coexisting COPD, which may contribute to the clinical treatment decisions.

High expression of SPP1 in patients with chronic obstructive pulmonary disease (COPD) is correlated with increased risk of lung cancer.

Chronic obstructive pulmonary disease (COPD) is characterized by persistent airway inflammation and fixed airflow obstruction. Patients with COPD have increased risk of lung cancer (LC), and the coexistence of both diseases is associated with poorer survival. However, the mechanisms predisposing patients with COPD to LC development and poor prognosis remain unclear. Gene expression profiles were downloaded from the Gene Expression Omnibus. Twenty-two data sets were included (n = 876). We identified 133 DEGs and 145 DEGs in patients with COPD and LC compared with healthy controls, respectively. There were 1544 DEGs in patients with LC and coexisting COPD compared with COPD, and these DEGs are mainly involved in the cell cycle, DNA replication, p53 signalling and insulin signalling. The biological processes primarily associated with these DEGs are oxidation reduction and apoptosis. SPP1 was the only overlapping DEG that was up-regulated in patients with COPD and/or LC, and this was validated by qPCR in an independent cohort. The area under the curve value for SPP1 was 0.893 (0.822-0.963) for the prediction of LC in patients with COPD. High expression of SPP1 in patients with LC was associated with shorter survival time. Up-regulation of SPP1 may be associated with increased risk of LC in patients with COPD and therefore may have potential as a therapeutic target for LC in patients with COPD.

Fluorescence imaging and Raman spectroscopy applied for the accurate diagnosis of breast cancer with deep learning algorithms.

Deep learning is usually combined with a single detection technique in the field of disease diagnosis. This study focused on simultaneously combining deep learning with multiple detection technologies, fluorescence imaging and Raman spectroscopy, for breast cancer diagnosis. A number of fluorescence images and Raman spectra were collected from breast tissue sections of 14 patients. Pseudo-color enhancement algorithm and a convolutional neural network were applied to the fluorescence image processing, so that the discriminant accuracy of test sets, 88.61%, was obtained. Two different BP-neural networks were applied to the Raman spectra that mainly comprised collagen and lipid, so that the discriminant accuracy of 95.33% and 98.67% of test sets were gotten, respectively. Then the discriminant results of fluorescence images and Raman spectra were counted and arranged into a characteristic variable matrix to predict the breast tissue samples with partial least squares (PLS) algorithm. As a result, the predictions of all samples are correct, with minor error of predictive value. This study proves that deep learning algorithms can be applied into multiple diagnostic optics/spectroscopy techniques simultaneously to improve the accuracy in disease diagnosis.

A Sputum 6 Gene Expression Signature Predicts Inflammatory Phenotypes and Future Exacerbations of COPD.

Background: The 6 gene expression signature (6GS) predicts inflammatory phenotype, exacerbation risk, and corticosteroid responsiveness in asthma. In COPD, patterns of airway inflammation are similar, suggesting the 6GS may be useful. This study determines the diagnostic and prognostic ability of 6GS in predicting inflammatory phenotypes and exacerbation risk in COPD. Methods: We performed 2 studies: a cross-sectional phenotype prediction study in stable COPD (total N=132; n=34 eosinophilic (E)-COPD, n=42 neutrophilic (N)-COPD, n=39 paucigranulocytic (PG)-COPD, n=17 mixed-granulocytic (MG)-COPD) that assessed 6GS ability to discriminate phenotypes (eosinophilia≥3%; neutrophilia≥61%); and a prospective cohort study (total n=54, n=8 E-COPD; n=18 N-COPD; n=20 PG-COPD; n=8 MG-COPD, n=21 exacerbation prone (≥2/year)) that investigated phenotype and exacerbation prediction utility. 6GS was measured by qPCR and evaluated using multiple logistic regression and area under the curve (AUC). Short-term reproducibility (intra-class correlation) and phenotyping method agreement (κ statistic) were assessed. Results: In the phenotype prediction study, 6GS could accurately identify and discriminate patients with E-COPD from N-COPD (AUC=96.4%; p<0.0001), PG-COPD (AUC=88.2%; p<0.0001) or MG-COPD (AUC=86.2%; p=0.0001), as well as N-COPD from PG-COPD (AUC=83.6%; p<0.0001) or MG-COPD (AUC=87.4%; p<0.0001) and was reproducible. In the prospective cohort study, 6GS had substantial agreement for neutrophilic inflammation (82%, κ=0.63, p<0.001) and moderate agreement for eosinophilic inflammation (78%, κ=0.42, p<0.001). 6GS could significantly discriminate exacerbation prone patients (AUC=77.2%; p=0.034). Higher IL1B levels were associated with poorer lung function and increased COPD severity. Conclusion: 6GS can significantly and reproducibly discriminate COPD inflammatory phenotypes and predict exacerbation prone patients and may become a useful molecular diagnostic tool assisting COPD management.

The Effects and Safety of Chinese Oral Herbal Paste on Stable Chronic Obstructive Pulmonary Disease: A Systematic Review and Meta-analysis of Randomized Controlled Trials.

BACKGROUND: Chinese oral herbal paste has been widely used in the treatment of chronic obstructive pulmonary disease (COPD). However, the treatment effects of herbal paste were controversial and lack evidence to support its clinical use. This study aims to systematically assess the efficacy and safety of Chinese oral herbal paste for the treatment of stable COPD. METHODS: PubMed, Web of Science, CENTRAL, EMBASE, CNKI, VIP, CBM, and WANFANG database in addition to two websites of clinical trial registry were searched from respective inception to August 2019. Only randomized controlled trials (RCTs) studying Chinese herbal paste for the treatment of stable COPD were included. Methodological quality was assessed based on Cochrane risk of bias and GRADE approach. Data were analyzed using RevMan 5.3. RESULTS: A total of 19 RCTs with 1303 individuals compared Chinese oral herbal paste and Western medicine (WM) with WM alone were included for meta-analysis. The review showed compared with WM alone, the combination of herbal paste and WM reduced exacerbation frequency. Subgroup analyses showed that after two to three months of treatment, compared with WM alone, Chinese herbal paste plus WM significantly decreased the St George's Respiratory Questionnaire (SGRQ) scores, COPD assessment test (CAT) scores, and scores of traditional Chinese medicine (TCM) syndrome, and improved clinical effective rates, lung function, and 6-minute walk distance. No serious adverse events related to herbal paste were reported. CONCLUSION: Current evidence showed that Chinese oral herbal paste may be an effective and well-tolerated adjuvant therapy for stable COPD. Considering the risks of bias and heterogeneity, more high-quality, well-designed RCTs are still needed.

Endotype-driven prediction of acute exacerbations in chronic obstructive pulmonary disease (EndAECOPD): protocol for a prospective cohort study.

INTRODUCTION: Current strategies for the prevention of acute exacerbations in chronic obstructive pulmonary disease (COPD) are primarily based on clinical measurements but fail to target the pathophysiological mechanisms, namely endotypes, of the disease. Studies identifying endotypes underlying exacerbation susceptibility and discovering specific biomarkers may lead to the development of targeted therapeutics but are lacking. This study aims to assess a broad spectrum of biomarkers at multiple biological levels (genetics, airway inflammation and respiratory microbiome) for their ability in predicting acute exacerbations of COPD, thus enables high-resolution disease endotyping and may lead to precision treatment of the disease. METHODS AND ANALYSIS: In this prospective cohort study, participants with stable COPD (n=600) will be recruited and assessed for demographics, symptom scores, spirometry, medication use and comorbidities at baseline. Blood will be obtained for genotyping variants in a panel of nine genes. Induced sputum will be collected for the profile of microbiota using 16S rRNA gene sequencing, quantification of bacterial load, inflammatory mediators assay and sputum cytometry. Participants will be followed up for their exacerbations till 12 months and reassessed for the clinical measurements as baseline. The primary outcomes are total number of exacerbations, severe exacerbations, moderate exacerbations and time to first exacerbation. The secondary outcomes are changes in lung function and symptom scores. The effect of biomarkers representing genetic variants, airway inflammation and respiratory microbiome on predicting the frequent exacerbator phenotype and exacerbation frequency will be analysed with multivariable modelling, and time to first exacerbation with a Cox regression model. ETHICS AND DISSEMINATION: The study has been approved by the Clinical Trial and Biomedical Ethics Committee of West China Hospital of Sichuan University (No. 2018-298). The results of the study will be published on peer-reviewed journals. TRIAL REGISTRATION NUMBER: ChiCTR1800019063.

Chinese Herbal Medicine Versus Placebo for the Treatment Of Chronic Obstructive Pulmonary Disease: A Protocol of Systematic Review and Meta-analysis.

BACKGROUND: Chinese herbal medicine (CHM) has been shown to be effective in the treatment of stable chronic obstructive pulmonary disease (COPD) by published meta-analyses. However, disease outcomes were inconsistent and heterogeneity was observed attributed to placebo-controlled studies. We present a protocol for a systematic review aiming to evaluate the clinical efficacy and safety of CHM comparing to placebo in the treatment of stable COPD, to provide robust evidence for the use of CHM in COPD. METHODS: We will comprehensively search the following 9 databases from inception to March 2019: Web of Science, PubMed, EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL), Chinese National Knowledge Infrastructure (CNKI), WANFANG Database, Chinese Scientific and Technological Periodical Database (VIP) and Chinese Biomedical Database (CBM), and the Cochrane Library database. All clinical randomized controlled trials comparing CHM to placebo for the treatment of stable COPD in English or Chinese will be included. The primary outcome will be quality of life, symptom score and exacerbation frequency, and the secondary outcomes include traditional Chinese medicine syndrome score and effective rate, lung function, 6-minute walk distance, and adverse events. Data extraction and quality assessment will be performed independently by 2 reviewers. Data synthesis and risk of bias will be assessed using the Review Manager software. This protocol will be conducted according to the Preferred Reporting Item for Systematic Review and Meta-analysis Protocols (PRISMA-P) guidance. RESULTS: This systematic review and meta-analysis will provide a high-quality comprehensive evaluation of the efficacy and safety based on current literature evidence of CHM intervention for stable COPD. CONCLUSION: The conclusion of this study will present the evidence of whether CHM is an effective and safe intervention for stable COPD patients.

Chinese oral herbal paste for the treatment of stable chronic obstructive pulmonary disease: Protocol for a systematic review and meta-analysis.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a common chronic respiratory disease with high morbidity and mortality placing heavy social and economic burden. As a kind of complementary therapy for the treatment of stable COPD, Chinese oral herbal paste has been widely used and studied. The study aims to evaluate the clinical efficacy and safety of herbal paste in the treatment of stable COPD, and to provide evidence for its clinical application. METHODS: We will electronically search databases, including Cochrane Central Register of Controlled Trials (CENTRAL), Web of Science, EMBASE, PubMed, Chinese National Knowledge Infrastructure (CNKI), WANFANG Database, Chinese Scientific and Technological Periodical Database (VIP), and Chinese Biomedical Database (CBM), from respective inception to June 2019 to collect randomized controlled trials (RCTs) of Chinese oral herbal paste for the treatment of stable COPD. The websites of Chinese clinical trial registry and international clinical trial registry, the reference lists of the retrieved articles, conference proceedings, and gray literature will also be collected. The quality of life, symptom scores, and exacerbation frequency will be measured as primary outcomes. Secondary outcomes include scores of traditional Chinese medicine (TCM) syndrome, clinical effective rates according to criteria in TCM, changes in lung function, 6-minute walking distance, and safety analysis. The Cochrane bias risk assessment and the GRADE method will be used to assess the quality of the original studies included. Merging analysis of data will be performed using Rev Man 5.3 software. RESULTS: The systematic review will provide an evidence on the clinical efficacy and safety of Chinese oral herbal paste for the treatment of stable COPD, and will be submitted for publication in a peer-reviewed journal. CONCLUSION: The study will confirm whether Chinese oral herbal paste is an effective and safe intervention for the prevention and treatment of stable COPD.

VDR rs7975232/ApaI genetic variation predicts sustained HBsAg loss in HBeAg-positive chronic hepatitis B patients treated with pegylated interferon.

AIM: To evaluate the predictive value of vitamin D and its metabolic pathway gene polymorphisms in response to pegylated interferon (Peg-IFN) in hepatitis B early antigen (HBeAg)-positive chronic hepatitis B (CHB) patients. METHODS: One hundred and nineteen HBeAg-positive CHB patients who received Peg-IFN monotherapy for 48 weeks and then were followed-up for another 48 weeks were prospectively enrolled; baseline 25-hydroxy vitamin D (25-(OH)D) and hepatitis B virus serologic marker levels were detected, nine critical single nucleotide polymorphisms within vitamin D metabolism were genotyped. RESULTS: Forty-five (37.8%), 44 (37.0%), 35 (29.4%), and 11 (9.2%) of the patients achieved virological response (VR), HBeAg loss, combined response (CR), and hepatitis B surface antigen (HBsAg) level < 200 IU/mL at the end of treatment (EOT; week 48), respectively; 42 (35.3%) and six (5.0%) people achieved HBeAg and HBsAg loss at the end of follow-up (EOF; week 96). Baseline HBeAg level was independent predictor of VR (odds ratio [OR], 0.470; 95% confidence interval [CI], 0.294-0.751; P = 0.002), HBeAg loss (OR, 0.395; 95% CI, 0.243-0.643; P < 0.001), CR (OR, 0.392; 95% CI, 0.215-0.714; P = 0.002) at EOT and HBeAg loss at EOF (OR, 0.334; 95% CI, 0.203-0.559; P < 0.001); baseline HBsAg level itself was independent predictor of both HBsAg < 200 IU/mL at EOT (OR, 0.257; 95% CI, 0.103-0.642; P = 0.004) and HBsAg loss at EOF (OR, 0.232; 95% CI, 0.077-0.702; P = 0.010). Age was also independent predictors of HBsAg loss at EOF (OR, 0.775; 95% CI, 0.634-0.948; P = 0.013). Concerning genetic variation of VDR rs7975232/ ApaI, A allele was the genetic independent predictor of VR at EOT (OR, 1.824; 95% CI, 1.024-3.248; P = 0.041) and HBsAg loss at EOF (OR, 3.566; 95% CI, 1.057-12.029; P = 0.040). CONCLUSIONS: Genetic variation of VDR rs7975232/ ApaI is a pretreatment predictor of sustained HBsAg loss in HBeAg-positive CHB patients with Peg-IFN monotherapy.

Sputum signatures for invasive pulmonary aspergillosis in patients with underlying respiratory diseases (SPARED): study protocol for a prospective diagnostic trial.

BACKGROUND: Invasive pulmonary aspergillosis (IPA) has been increasingly reported in patients with underlying respiratory diseases (URD). Early diagnosis of IPA is crucial for mortality reduction and improved prognosis, yet remains difficult. Existing diagnostic tools for IPA largely rely on the detection of biomarkers based on serum or bronchoalveolar lavage fluid (BALF), both of which have their limitations. The use of sputum sample is non-invasive, and Aspergillus detection is feasible; however, the usefulness of sputum biomarkers for the diagnosis of IPA, especially in patients with URD, has not been systematically studied. METHODS: This is a prospective diagnostic trial. At least 118 participants will be recruited from respiratory wards and intensive care units. IPA is defined according to the EORTC/MSG criteria modified for patients with URD. Induced sputum and blood will be collected, and BALF will be obtained by bronchoscopy. Sputum biomarkers, including galactomannan, Aspergillus DNA, triacetylfusarinine and bis(methylthio)gliotoxin will be determined, and the presence of a JF5 antigen will be examined with a lateral fluid device. The sensitivity, specificity, negative predictive value, positive predictive value and diagnostic odds ratio will be computed for different biomarkers and compared using the McNemar χ2 test. Receiver operating characteristic analyses will be performed, and the cut-off values will be established. Participants will receive follow-up evaluations at 3 months and 6 months after recruitment. The difference in hospital stay and survival will be analysed, and the relationships between the levels of biomarkers and hospital stay and survival will be analysed via regression models. DISCUSSION: We have developed and verified the feasibility of Aspergillus-related biomarker assays for sputum. The study findings will contribute to a novel look at the diagnostic performance of sputum biomarkers in IPA and provide important insight into the improvement of the early diagnosis of IPA, particularly in patients with URD. TRIAL REGISTRATION: This study has been registered with the Chinese Clinical Trial Registry ( ChiCTR-DPD-16009070 ) on 24th of August 2016.

Role of interleukin-21 and interleukin-21 receptor polymorphisms in the treatment of HBeAg-positive chronic hepatitis B patients with peginterferon.

The aim of this study was to evaluate the relationship between interleukin-21 (IL-21) and interleukin-21 receptor (IL-21R) polymorphisms and the response to peginterferon alfa (PEG-IFN α) therapy in HBeAg-positive chronic hepatitis B (CHB) patients.A total of 143 HBeAg-positive CHB patients treated for 48 weeks with PEG-IFN α and followed up for 24 weeks post-treatment were retrospectively evaluated. Genotypes analysis was performed for IL-21 polymorphisms rs907715, rs2221903, and IL-21R polymorphisms rs3093301 and rs2285452. Serum IL-21 levels were measured by enzyme-linked immunosorbent assay.The end of virological response (EVR) rate was 46.9% (67/143) at the end of treatment, the sustained virological response (SVR) rate was 43.4% (62/143) and the complete response (CR) rate was 32.1% (46/143) at 24 weeks post-treatment. Patients who carried IL-21 rs 2221903 genotype AA had a rather higher rate of EVR (response rate: 52.4%, odds ratio [OR] 0.42, 95% confidence interval [CI]: 0.19-0.91, P = .021), SVR (response rate: 47.6%, OR 0.43, 95% CI: 0.19-0.95, P = .028), and CR (response rate: 38.1%, OR 0.31, 95% CI: 0.12-0.79, P = .014) when compared to those had AG genotype. Meanwhile, IL-21rs 2221903 genotype AA was also independently associated with markedly reduced HBsAg levels (>1og10 IU/mL) after 24 weeks treatment and low HBsAg levels (<100 IU/mL) at the end of treatment. IL-21 rs907715 AG/GG genotype was independently associated with SVR (OR: 2.92, 95% CI: 0.98-8.6, P = .039; OR: 3.23, 95% CI: 1.0-10.4, P = .039). Patients with IL-21 rs907715 AG/GG genotype had higher serum IL-21 levels than those with rs907715 AA genotype (P = .021).IL-21 rs2221903 and rs907715 polymorphisms were significantly associated with the treatment response to PEG-IFN α among Chinese HBeAg-positive CHB patients.