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.

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.

Sputum mast cell subtypes relate to eosinophilia and corticosteroid response in asthma.

Mast cells are a resident inflammatory cell of the airways, involved in both the innate and adaptive immune response. The relationship between mast cells and inflammatory phenotypes and treatment response of asthma is not clear.Clinical characteristics of subjects with stable asthma (n=55), inflammatory cell counts and gene expression microarrays in induced sputum were analysed. Sputum mast cell subtypes were determined by molecular phenotyping based on expression of mast cell biomarkers (tryptase (TPSAB1), chymase (CMA1) and carboxypeptidase A3 (CPA3)). Effects of mast cell subtypes on steroid response were observed in a prospective cohort study (n=50).MCT(n=18) and MCT/CPA3(mRNA expression of TPSAB1 and CPA3; n=29) subtypes were identified, as well as a group without mast cell gene expression (n=8). The MCT/CPA3 subtype had elevated exhaled nitric oxide fraction, sputum eosinophils, bronchial sensitivity and reactivity, and poorer asthma control. This was accompanied by upregulation of 13 genes. Multivariable logistic regression identified CPA3(OR 1.21, p=0.004) rather than TPSAB1(OR 0.92, p=0.502) as a determinant of eosinophilic asthma. The MCT/CPA3 subtype had a better clinical response and reduced signature gene expression with corticosteroid treatment.Sputum mast cell subtypes of asthma can be defined by a molecular phenotyping approach. The MCT/CPA3 subtype demonstrated increased bronchial sensitivity and reactivity, and signature gene expression, which was associated with airway eosinophilia and greater corticosteroid responsiveness.

Association between histone hyperacetylation status in memory T lymphocytes and allergen-induced eosinophilic airway inflammation.

BACKGROUND AND OBJECTIVE: T lymphocytes, which are characterized by longevity and immune memory, play an important role in airway inflammation in asthma. Here, we assessed the association between immune memory and histone deacetylation and/or acetylation status. METHODS: CD4 + CD45RB(low) cells (memory T (Tm)) obtained from the spleens of asthma mice models were co-cultured with glucocorticoids (GCs), trichostatin A (TSA) or anacardic acid (AA) and adoptively transferred to naïve mice. Interleukin (IL)-4, 5 and 13 and IFN-γ concentrations were measured in culture supernatants and bronchoalveolar lavage fluid (BALF). Histone deacetylase (HDAC) and histone acetyltransferase (HAT) activities and the expression of T-bet, GATA-3, HDACs 1-11 and alveolar eosinophilic inflammation index (AEII) were determined in lung tissues. RESULTS: Culture supernatants and the BALF showed similar cytokine profiles. AA and GCs significantly inhibited HAT activity (P = 0.002 and P = 0.018), whereas TSA inhibited and GCs promoted HDAC activity (P = 0.004 and P = 0.025). HDACs 7, 9 and 10 were upregulated by AA and GCs (all P < 0.032), while HDAC11 was upregulated by GCs (P = 0.028). GC-induced inhibition of Tm histone acetylation alleviated AEII by downregulating IL-4, 5 and 13, similar to the effect of AA. CONCLUSION: Histone hyperacetylation status induced by low expression of HDACs 7, 9 and 10 in allergen-specific Tm cells contributes to eosinophilic airway inflammation. The mechanism by which GCs improve airway inflammation involves the upregulation of HDACs 7, 9, 10 and 11 and especially HDAC-10. The role of individual HDACs and AA as novel therapeutic agents for allergic asthma needs to be explored in the future.

Asthma control: how it can be best assessed?

PURPOSE OF REVIEW: A control-based asthma assessment is recommended by guidelines, but questions remain about how to assess the level of asthma control, and how current control status relates to future risks and biomarkers of disease pathogenesis. This review summarizes recent published data relating to asthma control and describes the challenges created by currently available instruments. RECENT FINDINGS: The current literature continues to show the widespread use of various assessment instruments for asthma control, in particular those with composite scores. However, poor correlations exist between the different assessment tools, and these instruments lack diagnostic accuracy to differentiate uncontrolled asthma. Whereas the concept of asthma control has been extended to add an assessment of future risks to the clinical control, clinical asthma control as measured by current available assessment tools does not necessary relate to the intrinsic disease activity which is typically characterized by inflammation in asthma. SUMMARY: The application of asthma control assessment represents an improvement in asthma management. The measurement of underlying disease activity potentially by biomarkers to assess disease control will lead to an improved assessment of the overall control of asthma, and further studies addressing this are needed.

Longitudinal changes in clinical outcomes in older patients with asthma, COPD and asthma-COPD overlap syndrome.

BACKGROUND: The progression of obstructive airway diseases (OADs) including asthma, chronic obstructive pulmonary disease (COPD) and asthma-COPD overlap syndrome in older adults is not well understood. OBJECTIVE: To examine the prognosis of OADs and to identify potential determinants for longitudinal changes in clinical outcomes. METHODS: We consecutively recruited 99 older adults (>55 years) with OADs who underwent a multidimensional assessment at baseline and 4 years which involved spirometry, 6-min walk distance (6MWD), assessments of health status (Saint George's Respiratory Questionnaire, SGRQ), comorbidity, and serum and sputum biomarkers. All-cause mortality and respiratory hospitalisation during the follow-up period were recorded. Clinical outcomes were compared between basal and final visits, and changes in clinical outcomes were compared among asthma, COPD and asthma-COPD overlap groups. Associations between clinical parameters, biomarkers and prognosis were examined. RESULTS: After a median follow-up of 4.2 years, outcome data were available for 75 (75.8%) patients. There were 16 (16.2%) deaths. The BODE index predicted all-cause mortality in older people with OADs. While spirometry, 6MWD and SGRQ deteriorated significantly over the 4 years, there was significant heterogeneity in the longitudinal changes in these clinical outcomes. Participants with COPD had a significant decline in FEV1 (p = 0.003), SGRQ (p = 0.030) and 6MWD [decline of 75.5 (93.4) m, p = 0.024]. The change in 6MWD was lower in the asthma-COPD overlap group. Airflow reversibility was associated with a reduced decline in 6MWD. CONCLUSION: COPD patients had a poor prognosis compared with asthma and asthma-COPD overlap patients. The BODE index is a useful prognostic indicator in older adults with OADs. Both airway disease diagnosis and BODE index warrant specific attention in clinical practice.

The Asthma Control Test and Asthma Control Questionnaire for assessing asthma control: Systematic review and meta-analysis.

BACKGROUND: Currently, the cornerstone of asthma management is the achievement and maintenance of optimal asthma control, but the diagnostic performances of the Asthma Control Test (ACT) and Asthma Control Questionnaire (ACQ) have not been evaluated systematically. OBJECTIVE: We explored the diagnostic performances of and statistically compared the ACT and ACQ. METHODS: Studies that examined the accuracy of the ACT, ACQ, or both in the assessment of asthma control were found by searching PubMed, CENTRAL, Web of Science, Ovid, and Embase. Summary estimates of sensitivity, specificity, and diagnostic odds ratios for the different levels of asthma control were determined by using bivariate random-effects models and hierarchical summary receiver operating characteristic models. RESULTS: Twenty-one studies with 11,141 subjects assessed with the ACT and 12,483 assessed with the ACQ were identified. The ACT had good diagnostic accuracy for assessment of controlled and not well-controlled asthma, and the ACQ (ACQ-7 and ACQ-6) had good diagnostic accuracy for assessment of not well-controlled asthma at prespecified cutoff points. The ACT and ACQ had significant differences in the assessment of controlled and not well-controlled asthma after adjusting for potential factors (P = .001 and P = .015). For assessment of uncontrolled asthma, the ACT had poor accuracy, with a hierarchical summary receiver operating characteristic area under the curve of 0.69, and the cutoff point for the ACQ has not been established. CONCLUSION: The ACT is preferable to the ACQ in clinical practice, and the ACQ requires further cross-validation. Moreover, neither the ACT nor the ACQ is useful for the assessment of uncontrolled asthma.

Andrographolide Attenuates NLRP3 Inflammasome Activation and Airway Inflammation in Exacerbation of Chronic Obstructive Pulmonary Disease.

Purpose: The aim of this study is to uncover the anti-inflammatory propertity of andrographolide (AGP) in acute exacerbation of chronic obstructive pulmonary disease (AECOPD) and the underlying mechanisms related to the nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome pathway. Methods: An in vivo experiment was conducted on murine model of AECOPD through endotracheal atomization of elastase and lipopolysaccharide (LPS). Intraperitoneal AGP was administered four times. NLRP3 inflammasome pathway molecules were examined using real-time quantitative polymerase chain reaction (RT-qPCR) and Western blot analysis. By using enzyme-linked immunosorbent assay (ELISA), we tested interleukin (IL)-1ß levels in bronchoalveolar lavage fluid. An in vitro study was conducted to determine how AGP impacts the NLRP3 inflammasome in THP-1 derived macrophages. The levels of molecules involved in the pathway were measured. Furthermore, molecular docking analyses were carried out to investigate the interactions between AGP and pathway targets. Results: In the in vivo study, NLRP3 inflammasome activation was observed in mice experiencing AECOPD. The administration of high-dose AGP demonstrated a mitigating effect on inflammatory cells infiltration in the lungs. Moreover, AGP administration effectively suppressed the expression of NLRP3, apoptosis associated speck-like protein that contains a CARD (PYCARD), cysteinyl aspartate-specific protease-1 (Caspase-1), IL-1ß, and IL-18 at both the genetic and protein levels. In the in vitro experiment, IL-1ß levels were significantly elevated in THP-1 derived macrophages with activated inflammasome compared to the control group. Furthermore, the downregulation of NLRP3, CASP1, and IL1B genes was observed upon the inhibition of NLRP3 expression through small interfering RNA (siRNA). AGP demonstrated inhibitory effects on the gene expression and protein levels of NLRP3, Caspase-1, and IL-1ß. Additionally, molecular docking analysis confirmed that AGP exhibited a favorable binding affinity with all five targets of the pathway. Conclusion: AGP effectively inhibited NLRP3 inflammasome activation and mitigated the inflammatory reaction of AECOPD both in animal models and in vitro experiments, highlighting the potential of AGP as a treatment for AECOPD with anti-inflammatory properties.

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

Background: Dyspnea, a common symptom of chronic respiratory diseases (CRDs), is closely linked to higher levels of functional impairment and death, leading to significant societal and financial challenges. Despite numerous clinical trials and systematic reviews suggested the potential benefits of acupuncture for chronic obstructive pulmonary disease (COPD) and lung cancer, there is currently insufficient evidence to conclusively prove its effectiveness in alleviating dyspnea in patients with CRDs. Methods: To compile and evaluate the existing data on the effectiveness and safety of acupuncture for managing dyspnea in CRDs. Randomized controlled trials investigating acupuncture for the treatment of dyspnea in patients with CRDs, such as COPD, lung cancer, asthma, bronchiectasis, interstitial lung disease, chronic pulmonary heart disease and bronchitis, were searched and retrieved from five electronic databases in English or Chinese. Results: A total of 23 studies meeting the inclusion criteria were found in databases, covering various CRDs such as COPD, lung cancer, and asthma. A meta-analysis that compared acupuncture to a control group (which included no acupuncture and sham acupuncture) found significant advantages for acupuncture in reducing dyspnea severity (P = 0.0003), increasing 6MWD (P < 0.00001), improving quality of life measured by St. George's Respiratory Questionnaire (P = 0.03) and karnofsky performance status score (P < 0.00001). No significance was found in breathing physiology represented by FEV1 (P = 0.34) and FVC (P = 0.15). There was a comparable incidence of negative outcomes in both groups (P = 0.07). Results were consistent when compared to sham acupuncture. In addition, subgroup analyses were also consistent when different diseases or types of acupuncture were analyzed. Conclusions: Acupuncture may be an effective and safe non-pharmacological complementary intervention to relief dyspnea for patients with CRDs. Nevertheless, research with high quality and large sample sizes is needed for further investigation.

[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.

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.

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.

[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.

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.

Relationship between current psychological symptoms and future risk of asthma outcomes: a 12-month prospective cohort study.

BACKGROUND: Subjects with asthma are more susceptible to psychological symptoms, but it is uncertain whether psychological symptoms are linked to future risk of asthma outcomes. OBJECTIVE: To investigate the relationship between current psychological symptoms and future risk of asthma outcomes. METHODS: We conducted a prospective cohort study with a 12-month follow-up period of 297 patients with asthma. Psychological symptoms, lung function, asthma control test, and Asthma Quality of Life Questionnaire at baseline were assessed. Asthma outcomes including exacerbations, unplanned visits, emergency visits, hospital admissions, intensive care unit admissions, and length of hospital stays were monitored monthly. The time to the first asthma outcomes was analyzed. Furthermore, the association between psychological symptoms and future risk of asthma outcomes was calculated as adjusted relative risk (RR) using logistic regression models. RESULTS: The asthma patients were assigned to one of three groups: neither anxiety nor depression symptoms (NAD, n = 102), either anxiety or depression symptoms (A/D, n = 68), or anxiety and depression symptoms (AD, n = 120). Logistic regression models indicated that asthma patients in the AD group, but not the A/D group, had an increased adjusted RR for unplanned visits and emergency visits (RR = 2.33, 95% confidence interval (CI) = [1.50, 3.61]; and RR = 3.13, 95% CI = [1.90, 5.17], respectively). The time to the first asthma outcomes including exacerbations, unplanned visits, and emergency visits was shorter in patients with psychological symptoms than those without (all p < .001). CONCLUSION: Current psychological symptoms, especially anxiety combined with depression, independently predict the future risk of asthma outcomes. Ting Zhou and Lan Wang contributed equally to this study.

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.