Identification of key modules and hub genes for eosinophilic asthma by weighted gene co-expression network analysis.

OBJECTIVE: Eosinophilic asthma (EA) is one of the most important asthma phenotypes with distinct features. However, its genetic characteristics are not fully understood. This study aimed to investigate the transcriptome features and to identify hub genes of EA. METHODS: Differentially expressed genes (DEGs) analysis, weighted gene coexpression network analysis (WGCNA) and protein-protein interaction (PPI) network analysis were performed to construct gene networks and to identify hub genes. Enrichment analyses were performed to investigate the biological processes, pathways and immune status of EA. The hub genes were validated in another dataset. The diagnostic value of the identified hub genes was assessed by receiver operator characteristic curve (ROC) analysis. RESULTS: Compared with NEA, EA had a different gene expression pattern, in which 81 genes were differentially expressed. WGCNA identified two gene modules significantly associated with EA. Intersections of the DEGs and the genes in the modules associated with EA were mainly enriched in chemotaxis and signal transduction by GO and KEGG enrichment analyses. Single-sample gene set enrichment analysis (ssGSEA) indicated that EA had different immune infiltration and functions compared with NEA. Seven hub genes of EA were identified and validated, including CCL17, CCL26, CD1C, CXCL11, CXCL10, CCL22, and CCR7, all of which have diagnostic values for distinguishing EA from NEA (All AUC > 0.7). CONCLUSIONS: This study demonstrated the distinct gene expression patterns, biological processes, and immune status of EA. Hub genes of EA were identified and validated. Our study could provide a framework of co-expression gene modules and potential therapeutic targets for EA.

Immunophenotype in acute exacerbation of chronic obstructive pulmonary disease: a cross-sectional study.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease, and the immune inflammatory response is thought to play an important role in pathogenesis. However, the immunophenotype of patients with COPD is unknown. Herein, we evaluated the immunophenotype of patients with acute exacerbation of COPD (AECOPD). METHODS: A cross-sectional study was conducted in West China Hospital from September 2018 to October 2019. The proportion of CD4 + T lymphocyte subtypes (Th1, Th2, Th17 and Treg) and levels of serum cytokines in the peripheral blood of patients with AECOPD, stable COPD (SCOPD), healthy smokers (HSs)and healthy controls (HCs) were evaluated. RESULTS: A total of 15 HCs, 19 HSs, 42 patients with SCOPD, and 55 patients with AECOPD were included. Compared to patients with SCOPD, Th1 cells, Th17 cells, Treg cell ratio, Th1/Th2 cell ratio, and the levels of C-reactive protein, interleukin (IL)-6, and IL-10 were significantly increased in patients with AECOPD (P < 0.001), while the proportion of Th2 cells was significantly reduced (P < 0.01). The proportion of Th17 cells was positively correlated with COPD Assessment Test score (r = 0.266, P = 0.009), modified Medical Research Council dyspnea score (r = 0.858, P < 0.0001), and Th1 cell ratio (r = 0.403, P < 0.0001) and negatively correlated with forced vital capacity (r = - 0.367, P = 0.009) and proportion of Th2 cells (r = - 0.655, P < 0.0001). CONCLUSIONS: The immunophenotype of patients with AECOPD shows abnormal activation of Th1, Th17, and Treg cells. There is a correlation between the proportion of Th17 cells and the severity of COPD; therefore, this may represent a novel index for the evaluation of COPD severity. TRIAL REGISTRATION: China Clinical Trials Registry, ChiCTR1800018452, registered 19 September 2018, https://www.chictr.org.cn/index.aspx .

SNHG17 upregulates WLS expression to accelerate lung adenocarcinoma progression by sponging miR-485-5p.

BACKGROUND: Long non-coding RNAs (lncRNAs) have been uncovered to be essential regulators in the biological processes of human cancers, including lung adenocarcinoma (LUAD). Recently, small nucleolar RNA host gene 17 (SNHG17) has been identified as one novel oncogenic lncRNA in gastric cancer. However, it remains unclear whether SNHG7 exert functions in LUAD progression. METHODS: The expression levels of SNHG17, miR-485-5p and Wnt ligand secretion mediator (WLS) in LUAD cells was evaluated by RT-qPCR. The effect of SNHG7 silencing on LUAD cell proliferation was assessed by colony formation and EdU assays. The apoptosis of LUAD cells was measured by flow cytometry analysis. Transwell assays were applied to detect cell migration and invasion. The relationship between SNHG17 and miR-485-5p was validated by RIP, RNA pull down and luciferase reporter assays. RESULTS: SNHG17 and WLS were up-regulated in LUAD cell lines. Down-regulation of SNHG17 curbed LUAD cell proliferation, migration and invasion but facilitated apoptosis. SNHG17 acted as miR-485-5p sponge to upregulate WLS expression. CONCLUSION: SNHG17 triggers the progression of LUAD via sponging miR-485-5p to upregulate WLS expression.

Dasatinib-induced chylothorax: report of a case and review of the literature.

Dasatinib is a tyrosine kinase inhibitor for the treatment of BCR-ABL-positive chronic myeloid leukaemia (CML) or Philadelphia chromosome-positive acute lymphoblastic leukaemia (ALL). Although fluid retention is a common adverse event associated with dasatinib, chylothorax is exceptionally rare. The pathological mechanism, clinical manifestation and management of dasatinib-induced chylothorax are completely unclear. A 71-year-old man treated with dasatinib for CML was admitted for progressive dyspnea. Computed tomography (CT) showed a pleural effusion that was more prominent on the right thoracic cavity. Thoracentesis showed thick milky pleural fluid, which was then confirmed as chylothorax by chylum qualitative tests and triglyceride measurements. Radionuclide lymphoscintigraphy yielded an obstruction at the end segment of the thoracic duct, but no leakage points were found. After excluding common causes, drug-induced chylothorax was presumed. Then, dasatinib was withdrawn, and 1 week later, chylothorax resolved. To further elucidate the relationship between the medication and chylothorax, dasatinib was resumed tentatively for 2 days. As expected, pleural effusion recurred soon. Based on these clinical manifestations, the diagnosis of dasatinib-induced chylothorax was identified. The patient was suggested to stop dasatinib and use an alternative drug as recommended by the haematologist. Pleural effusion is the common adverse reaction of dasatinib, but chylothorax is rare. Only six cases of dasatinib-induced chylothorax have been reported, and our patient is the seventh case. Once a patient with dasatinib treatment develops chylothorax, dasatinib should be considered one of the possible causes. If no other definitive aetiological factor is identified, dasatinib discontinuation might be the optimum scheme.

Efficacy and safety of dupilumab for the treatment of uncontrolled asthma: a meta-analysis of randomized clinical trials.

BACKGROUND: Several recent clinical trials have assessed the effects of dupilumab in uncontrolled asthma, but reached no definite conclusion. We therefore conducted this meta-analysis to evaluate the overall efficacy and safety of dupilumab for the treatment of uncontrolled asthma. METHODS: All randomized controlled trials were included. Standard mean differences (SMD) or relative risks (RR) were calculated using Fixed-or random-effects models. RESULTS: Five studies involving 3369 patients were identified. Pooled analysis showed significant improvements in the first-second forced expiratory volume (FEV1) (SMD = 4.29, 95% CI: 2.78-5.81) and Asthma Quality of Life Questionnaire scores (SMD = 4.39, 95% CI: 1.44-7.34). Dupilumab treatments were also associated with significantly decreased 5-item Asthma Control Questionnaire scores (SMD = - 4.95, 95% CI: - 7.30 to - 2.60), AM and PM asthma symptom scores (SMD = - 5.09, 95% CI: - 6.40 to - 3.77; SMD = - 4.92, 95% CI: - 5.98 to - 3.86, respectively), and severe exacerbation risk (RR = 0.73; 95% CI: 0.67-0.79) compared with placebo, with similar incidence of adverse events (RR = 1.0; 95% CI: 0.96-1.04). CONCLUSION: Dupilumab treatment is relatively well-tolerated and could significantly improve FEV1, symptoms, asthma control, and quality of life, and reduced severe exacerbation risk in patients with uncontrolled asthma.

Long-term follow-up of self-expandable metallic stents in benign tracheobronchial stenosis: a retrospective study.

BACKGROUND: Self-expandable metallic stents (SEMSs) have enabled a approving management of malignant airway stenosis. However, the long-term efficacy and safety of this treatment in patients with benign airway stricture are unclear. We conducted this study to retrospectively determine the efficacy and long-term outcomes in patients who have undergone SEMS placement for benign tracheobronchial stenosis. METHODS: All patients treated with SEMSs from July 2003 to June 2016 were reviewed for symptomatic response, complications, and long-term outcomes. RESULTS: Total 131 stents were successfully deployed in 116 patients. Ninety-eight patients demonstrated clinical improvement after stent insertion (84.48%; 95% confidence interval [CI]: 77.89-91.07). Compared with uncovered stents, covered stents were associated with more sore throats complaints or chest pain (13.89% versus 28.81%, P = 0.036) and with higher incidences of major and minor granulation tissue formation and with recurrent stenosis (4.17% versus 15.25%, P = 0.029; 11.11% versus 37.29%, P < 0.0001 and 9.72% versus 28.81%, P = 0.005, respectively). Each covered and uncovered stent developing tissue hyperplasia required a median of 2 (range: 1-15) and 1(range: 1-7) fibrobronchoscope with electrocautery therapy, respectively. At follow-up (median: 1276 days; range: 2-4263), 68 patients had complete resolution, 15 remained under interventional treatment, 8 had bronchial occlusions, 7 underwent surgery, 14 were lost to follow-up, and 4 died of stent unrelated causes. CONCLUSION: SEMS placement achieved most clinical improvement among patients in our study, if adequate endotracheal measures were used to address stent-related complications. The use of permanent SEMSs for benign tracheobronchial stenosis was effective and safe for the majority of patients in a long-term follow-up. TRIAL REGISTRATION: The study has been retrospectively registered in the China Clinical Trial Registry on October 21, 2018 (Registry ID: ChiCTR1800019024 ).

Effects of vitamin D supplementation on the outcomes of patients with pulmonary tuberculosis: a systematic review and meta-analysis.

BACKGROUND: Vitamin D is involved in the host immune response toward Mycobacterium tuberculosis. However, the efficacy of vitamin D supplementation on sputum conversion, clinical response to treatment, adverse events, and mortality in patients with pulmonary tuberculosis (PTB) remains controversial. We aimed to clarify the efficacy and safety of vitamin D supplementation in PTB treatment. METHODS: We searched Medline, Embase, Cochrane Central Register of Controlled Trials, Web of Science for double-blind, randomized controlled trials of vitamin D supplementation in patients with PTB that reported sputum conversion, clinical response to treatment, adverse events, or mortality, published from database inception to November 26, 2017. This study was registered with PROSPERO, number CRD42018081236. RESULTS: A total of 1787 patients with active PTB receiving vitamin D supplementation along with standard anti-tuberculosis regimen were included in the eight trials with different doses of vitamin D ranging from 1000 IU/day to 600,000 IU/month at different intervals. Primary analysis revealed that vitamin D supplementation increased the proportion of sputum smear and culture conversions (OR 1.21, 95%CI 1.05~ 1.39, z = 2.69, P = 0.007; OR 1.22, 95%CI 1.04~ 1.43, z = 2.41, P = 0.02), but did not improve the time to sputum smear and culture conversions (HR 1.07, 95%CI 0.83~ 1.37, z = 0.50, P = 0.62; HR 0.97, 95%CI 0.76~ 1.23, z = 0.29, P = 0.77). In the secondary analysis, vitamin D improved serum 25(OH)D, plasma calcium concentration, lymphocyte count, and chest radiograph (MD 103.36, 95%CI 84.20~ 122.53, z = 10.57, P < 0.00001; SMD 0.26, 95%CI 0.15~ 0.37, z = 4.61, P < 0.00001; MD 0.09, 95%CI 0.03~ 0.14, z = 2.94, P = 0.003); MD -0.33, 95% CI -0.57~ - 0.08 z = 2.57, P = 0.01), but had no impact on adverse events, mortality and other indicators(TB score, BMI, mean mid-upper arm circumference, weight gain, CRP, ESR, and other blood cells) (P > 0.05). CONCLUSIONS: Vitamin D supplementation can be considered as a combination therapy in patients with PTB.

Primary tracheal adenoid cystic carcinoma: adjuvant treatment outcome.

BACKGROUND: Adenoid cystic carcinoma (ACC) is the second most common tracheal tumor, but its optimal treatment strategy is still controversial. METHODS: To further elucidate the impact of treatment on disease-free survival (DFS) and overall survival (OS), we retrospectively investigated different treatment modalities and outcomes of 56 patients with primary ACC of the trachea treated at four hospitals in Sichuan Province of China from 1995 to 2012. RESULTS: 52 patients were included in the analysis. 4 patients with unresectable tumors were treated primarily with radiotherapy (RT) alone. 11 of 48 patients who received surgery as primary therapy obtained complete resection without adjuvant therapy. 24 of 37 patients who had incomplete resection (R1, R2) received postoperative RT while 13 patients were treated without postoperative RT. Postoperative chemotherapy (CT) was used in 12 patients with postoperative RT. No significant difference was shown in DFS (p = 0.683) and OS (p = 0.829) between patients with complete resection and those with incomplete resection. Postoperative RT for patients with incomplete resection was associated with improved DFS (92 vs. 62 months, p = 0.027) and OS (125 vs. 78 months, p = 0.004). Postoperative chemotherapy (CT) following RT did not have a significant impact on DFS (p = 0.390) or OS (p = 0.646) in patients with positive margin. CONCLUSIONS: These observations suggest that postoperative RT should probably be recommended for patients with incomplete resection. Postoperative CT following RT in patients with incomplete resection did not seem to produce an additional survival benefit.

Polymorphisms in a disintegrin and metalloprotease 33 gene and the risk of chronic obstructive pulmonary disease: a meta-analysis.

A number of polymorphisms in a disintegrin and metalloprotease 33 (ADAM33) gene have been implicated in susceptibility to chronic obstructive pulmonary disease (COPD). However, results to date have been inconclusive. We conducted meta-analyses to investigate the associations between multiple polymorphisms in ADAM33 gene and COPD susceptibility. PubMed, Embase and Chinese databases (Wanfang and China National Knowledge Infrastructure) were searched for eligible case-control studies. We extracted data and used meta-analysis to calculate pooled odds ratios with 95% confidence intervals to evaluate the strength of associations. Twelve studies containing six ADAM33 polymorphisms (F+1, S1, S2, T1, V4 and Q-1) were identified, which involved 2630 cases and 4376 controls. ADAM33 S1 polymorphism showed stable and significant associations with COPD risks among the Chinese and smoking populations, and Q-1 polymorphism showed stable and significant associations with COPD risks among the overall populations. In subgroup analyses, T1 and Q-1 polymorphisms were significantly associated with COPD risks among the Chinese and smoking populations, and among the Chinese, Caucasians and smoking populations, respectively. However, none of the significant results was stable in sensitivity analyses. With respect to F+1, S2 or V4 polymorphism, there was no evidence of any significant association with COPD risks in either the overall or the subgroup analysis. The results of this meta-analysis indicate that ADAM33 S1 polymorphism is a risk factor for COPD among the Chinese and smoking populations, and that Q-1 polymorphism is a risk factor for COPD among the overall populations.

Imaging-Guided Percutaneous Endovascular Biopsy Applied in Patients with Pulmonary Artery Masses: A Review.

INTRODUCTION: Pulmonary artery (PA) masses are rare. Distinguishing PA tumours from embolism is sometimes difficult, and surgical biopsy is expensive and risky. We aimed to evaluate the efficacy of imaging-guided percutaneous endovascular biopsy (PEB) for obtaining tissues for histological diagnosis. METHODS: We searched Cochrane, Medline, Embase, and Web of Science for PEB trials involving patients with PA masses, published from the inception of the database until August 2023. RESULTS: We retrospectively reviewed 33 studies including 87 patients (median age 55 ± 69.3 years, 44 men) with PA masses who underwent a total of 110 PEBs. Of these patients, 34.5% (n = 38) underwent PEB-catheter aspiration (PEB-CA), 50.9% (n = 56) underwent PEB-forceps biopsy (PEB-FB) and 2.7% (n = 3) underwent PEB-directional atherectomy (PEB-DA). The most common histological aetiology of PA masses was mesenchymal tumours (n = 67, 75.9%). Tumour embolism (n = 6, 6.9%) and pulmonary embolism (n = 3, 3.4%) were the second and third most common types of PA masses, respectively. The technical success rates of PEB-CA, PEB-FB and PEB-DA were 92.1%, 94.6% and 100% (p = 0.796), respectively. Histopathological analysis provided clinical diagnostic success rates of 44.7%, 85.7% and 100% for PEB-CA, PEB-FB and PEB-DA (p < 0.001), respectively. In pairwise comparison, PEB-FB had a higher success rate in pathological diagnosis than PEB-CA (p = 0.000). Apart from one patient suffering from haemorrhagic cardiac tamponade, no other complications occurred. CONCLUSION: Imaging-guided PEB is a safe and effective technique for the early pathological diagnosis of PA masses.

[Effects of diterpene phenol extract of Rosmarinus officinalis on TGFbeta1 and mRNA expressions of its signaling pathway molecules in the lung tissue of pulmonary fibrosis rats].

OBJECTIVE: To investigate the regulative mechanism of the diterpene phenol extract of Rosmarinus Officinalis (DERO) on the imbalance of collagen metabolism of the lung tissue in pulmonary fibrosis rats. METHODS: Fifty healthy Sprague-Dawley rats were randomly divided into the normal saline group (NS), the bleomycin-induced lung injury group (BLM), the low dose DERO group (at the daily dose of 50 mg/kg), the moderate dose DERO group (at the daily dose of 100 mg/kg), and the high dose DERO group (at the daily dose of 200 mg/kg), 10 in each group (abbreviated as DERO 1, 2, 3, respectively). The pulmonary fibrosis rat model was prepared by disposable intratracheal instillation of bleomycin. DERO was administered by gastrogavage as intervention during the repairing process of lung injury. On the morning of the 29th day, the rats' lung tissue was extracted. The karyocyte number, collagen protein, type I collagen (collagen I) and transforming growth factor-beta type II receptor (TGFbetaR II), Smad4 mRNA expressions were semi-quantitatively determined using tissue microarray, HE staining, collagen fiber dyeing, immunohistochemical assay, and in situ hybridization. Using real-time fluorescent quantification RT-PCR, the mRNA expression of transforming growth factor-beta1 (TGF-beta1) were detected. RESULTS: Compared with the NS group, the collagen deposition of the lung tissue was obvious and the inflammatory infiltration was more severe in the BLM group (P < 0.05, P < 0.01). There was no statistical difference in the aforesaid 4 indices between the DERO1 group and the BLM group (P > 0.05). The collagen deposition and the inflammatory infiltration were obviously alleviated in the DERO2 and DERO3 groups (P < 0.05, P < 0.01). Compared with the NS group, the mRNA expressions of collagen-I, TGF-beta1 R II, Smad4, and TGF-beta1 were obviously up-regulated in the BLM group (P < 0.05, P < 0.01). Compared with the BLM group, the aforesaid four indices were not statistically changed in the DERO1 group (P > 0.05). But the mRNA expressions of collagen-I, TGF-beta1 R II, Smad4, and TGF-beta1 were obviously downregulated in the DERO2 and DERO3 groups (P < 0.05, P < 0.01). But the down-regulation of Smad4 expression was not obvious in the DERO2 and the DERO3 groups (P > 0.05). Compared with the DERO1 group, the mRNA expressions of collagen-I, TGF-beta1, R II, TGFbeta1 were all obviously lower in the DERO2 and the DERO3 groups (P < 0.05). But there was no statistical difference in the aforesaid 4 indices between the DERO2 group and the DERO3 group (P > 0.05). CONCLUSIONS: DERO could regulate imbalanced collagen metabolism of pulmonary fibrosis. It could inhibit excessive deposition of collagen fibers, especially excessive deposition of collagen- I. Its mechanisms might be realized by inhibiting up-regulation of TGF-beta1 and TGFbetaR II mRNA expressions, thus interfering the activation of TGF-beta-Smad signaling pathway on target genes, especially on type I procollagen target gene.

[The clinical value of combining multiple features of CT in discriminating between benign and malignant lung lesions].

OBJECTIVE: To develop a set of combined criteria of multiple features of chest CT for discriminating between benign and malignant lung lesions. METHODS: Patients whose chest CT showed abnormalities were recruited from the West China Hospital in March and April 2010. The patients were examined with bronchoscopy and the results of CT and pathology were compared. RESULTS: A total of 105 patients participated in this study and 85 had confirmed pathological results. The CT identified 27 cases of malignant lesions, 22 of which were confirmed by the pathology. The CT identified 58 cases of benign lesions, 55 of which were confirmed by the pathology. The set of combined criteria of multiple features of chest CT had an accuracy of 90.59%, a sensitivity of 88.00%, and a specificity of 91.67% in diagnosing benign and malignant lung lesions. CONCLUSION: The combined criteria of multiple imaging signs of CT have good clinical values for diagnosing malignant lung lesions.

Extracorporeal membrane oxygenation in critical airway interventional therapy: A review.

Introduction: Extracorporeal membrane oxygenation (ECMO) is widely used during refractory cardiac or respiratory failure, and some case reports described ECMO utilization in critical airway interventional therapy. Methods: Eligible reports about patients receiving airway interventional therapy under ECMO were retrieved from Web of Science, Embase, Medline, and Cochrane databases up to 1 August 2022. Results: Forty-eight publications including 107 patients who underwent ECMO for critical airway problems met the inclusion criteria. The critical airway problem that was reported the most was tumor-associated airway obstruction (n = 66, 61.7%). The second most reported etiology was postoperative airway collapse or stenosis (n = 19, 17.8%). The main interventional therapies applied were airway stent placement or removal (n = 61, 57.0%), mass removal (n = 22, 20.6%), and endotracheal intubation (n = 12, 11.2%) by bronchoscopy. The median ECMO duration was 39.5 hours. Eleven patients had ECMO-associated complications, including seven cases of airway hemorrhage, one case of arteriovenous fistula, one case of vein rupture and hematoma, one case of foot ischemia, and one case of neuropraxia of the cannulation site. In total, 91.6% of the patients survived and were discharged from the hospital. Conclusion: ECMO appears to be a viable form of life support for patients undergoing interventional therapy for critical airway problems.

Clinical characteristics and risk factors of in-hospital mortality in patients coinfected with Pneumocystis jirovecii and Aspergillus.

OBJECTIVE: To analyze clinical characteristics and risk factors for in-hospital mortality in patients coinfected with P. jirovecii and Aspergillus. METHODS: This study included 53 patients with coinfection of P. jirovecii pneumonia (PJP) and invasive pulmonary aspergillosis (IPA) in our center from January 2011 to December 2021. All cases were divided into survivor (n=27) and non-survivor groups (n=26). Medical records, laboratory and radiology data were collected. Risk factors for in-hospital mortality were identified by multivariable analyses. RESULTS: HIV-positive patients accounted for 3.8%. Fever (77.4%), dyspnea (69.8%) and wet cough (24.5%) were common symptoms. Ground-glass opacity (83.0%), consolidation (71.7%), septal thickening (66.0%), and nodules (54.7%) were the most common radiological signs. CD4+ T cell count and serum albumin (ALB) level were significantly lower in non-survival group than in the survival group. Conversely, serum lactate dehydrogenase (LDH) and procalcitonin (PCT) levels were higher in non-survival group than in survival group. Lactic acidosis [odds ratio (OR): 33.999,95% confidential interval (CI): 3.112-371.409; p=0.004], low CD4+ T cell count (<114 cell/µL) [OR: 19.343, 95% CI: 1.533-259.380; p=0.022] and high level of LDH (> 519 U/L) [OR: 11.422, 95% CI: 1.271-102.669; p=0.030] were independent risk factors for mortality. CONCLUSION: PJP coinfected with IPA incurs high mortality with nonspecific clinical characteristics and is more likely to involve HIV-negative patients. Lactic acidosis, low CD4+ T cell count and high LDH level are independent risk factors for mortality, close monitoring of these parameters is necessary to help distinguish high-risk patients and make appropriate clinical decisions.

Circ_0004140 promotes lung adenocarcinoma progression by upregulating NOVA2 via sponging miR-330-5p.

BACKGROUND: Circular RNAs (circRNAs) play a significant role in the tumorigenesis and progression of diverse human cancers, including lung adenocarcinoma. A previous study suggested that circ_0004140 expression was increased in lung adenocarcinoma cells. However, the molecular mechanism of circRNA circ_0004140 involved in lung adenocarcinoma is poorly defined. METHODS: Circ_0004140, microRNA-330-5p (miR-330-5p), and NOVA alternative splicing regulator 2 (NOVA2) expression were determined by real-time quantitative polymerase chain reaction (RT-qPCR). Cell proliferation, apoptosis, migration, invasion, and angiogenesis ability were assessed using 5-ethynyl-2'-deoxyuridine (EdU), flow cytometry, wound healing, transwell, and capillary-like network formation assays. Proliferating cell nuclear antigen (PCNA), cyclin D1, and NOVA2 protein levels were detected using Western blot assay. The interaction between miR-330-5p and circ_0004140 or NOVA2 was verified by dual-luciferase reporter assay. Xenograft tumor model was utilized to assess the role of circ_0004140 in tumor growth in vivo. RESULTS: Circ_0004140 was upregulated in lung adenocarcinoma tissues and cell lines. Circ_0004140 silencing suppressed cell proliferation, migration, invasion and tube formation ability, and triggered the apoptosis of lung adenocarcinoma cells. Circ_0004140 acted as a molecular sponge for miR-330-5p, and miR-330-5p silencing largely reversed circ_0004140 knockdown-induced effects in lung adenocarcinoma cells. NOVA2 was a target of miR-330-5p, and NOVA2 overexpression might largely overturn miR-330-5p overexpression-induced influences in lung adenocarcinoma cells. Circ_0004140 upregulated NOVA2 expression via sponging miR-330-5p in lung adenocarcinoma cells. Circ_0004140 silencing restrained xenograft tumor growth in vivo. CONCLUSION: Circ_0004140 knockdown might suppress the malignant biological behaviors of lung adenocarcinoma cells via miR-330-5p-dependent regulation of NOVA2.

Gabapentin for chronic refractory cough: A system review and meta-analysis.

Objective: To evaluate the efficacy and safety of gabapentin in the treatment of chronic refractory cough by Meta-Analysis. Methods: Literatures were retrieved from PubMed, Embase (OvidIP), Cochrane Library, CNKI, VIP, Wanfang Database and China Biomedical Management System and eligible prospective studies were screened. Data were extracted and analyzed by using RevMan 5.4.1 software. Results: Six articles (2 RCTs and 4 prospective studies) with 536 participants were finally included. Meta-analysis showed that gabapentin was better than placebo in cough-specific quality of life (LCQ score, MD = 4.02, 95%CI [3.26,4,78], Z = 10.34, P < 0.00001), cough severity (VAS score, MD = -29.36, 95% CI (-39.46, -19.26), Z = 5.7, P < 0.00001), cough frequency (MD = -29.87, 95% CI [- 43.84, -15.91], Z = 4.19, P < 0.0001) and therapeutic efficacy (RR = 1.37,95%CI [1.13,1.65], Z = 3.27, P = 0.001), and equal in safety (RR = 1.32,95%CI [0.47,3.7], Z = 0.53, P = 0.59). Gabapentin was similar to other neuromodulators in therapeutic efficacy (RR = 1.07,95%CI [0.87,1.32], Z = 0.64, P = 0.52), but its safety was better. Conclusion: Gabapentin is effective in the treatment of chronic refractory cough in both subjective and objective evaluations, and its safety is better than other neuromodulators.

Diagnostic accuracy of interleukin-2 receptor in sarcoidosis: a systematic review and meta-analysis.

INTRODUCTION: Soluble interleukin-2 receptor (sIL-2 R), a valuable diagnostic biomarker for sarcoidosis, has been reported with variable results. Based on the literatures currently accessible, a systematic review and meta-analysis of the diagnostic performance of serum sIL-2 R for sarcoidosis were performed. METHODS: Relevant studies investigating sIL-2 R for sarcoidosis diagnosis in several databases were searched and data on sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), and diagnostic odds ratio (DOR) were pooled by STATA 16.0 software. Overall test performance was assessed using summary receiver operating characteristic curves and the area under the curve (AUC). Potential publication bias was assessed by Deeks test. RESULTS: We included eleven studies involving 1,424 subjects, with 1,099 cases of sarcoidosis and 325 of non-sarcoidosis. The pooled parameters of sIL-2 R in diagnosing sarcoidosis were summarized as follows: sensitivity, 0.85 (95% CI: 0.72-0.93); specificity, 0.88 (95% CI: 0.72-0.96); PLR, 7.3 (95% CI: 2.7-20.1); NLR, 0.17 (95% CI:0.08-0.36); DOR, 44 (95% CI: 8-231); and the AUC, 0.93 (95% CI: 0.90-0.95). No publication bias was identified (P = 0.64). CONCLUSIONS: Evidence suggests sIL-2 R performs well in diagnosing sarcoidosis. Nevertheless, results of sIL-2 R assay should be interpreted with other diagnostic examinations.

Instillation of Amphotericin B by bronchoscopy combined with systemic voriconazole in advanced non-small cell lung cancer patients with chronic cavitary pulmonary aspergillosis: A case series and literature review.

Although the treatment of aspergillosis has been studied for years, the optimal nonsurgical treatment of chronic cavitary pulmonary aspergillosis (CCPA) remains unsatisfactory, especially in lung cancer. We report two advanced non-small cell lung cancer (NSCLC) patients who recovered from CCPA following instillation of Amphotericin B (AmB) by bronchoscopy combined with systemic voriconazole. The first patient was diagnosed with lung adenocarcinoma after right upper lobe resection and was treated with anaplastic lymphoma kinase-targeted therapy. Chest computed tomography (CT) revealed a right pulmonary cavity containing solid materials. The second patient was diagnosed with squamous cell carcinoma and received immunotherapy following surgery, chemotherapy, and radiotherapy. Chest CT tomography revealed a mass in the right lung cavity. Both patients' cultures and next-generation sequencing of their bronchoalveolar lavage (BAL) samples revealed presence of Aspergillus fumigatus. In addition, the galactomannan test of both patients BAL samples was positive. Systemic voriconazole was prescribed based on in vitro susceptibility testing. The chest images and clinical symptoms of both patients did not improve after one month of voriconazole therapy within the therapeutic blood concentration. Considering the low local concentrations of antifungals against CCPA, AmB instillation by bronchoscopy combined with systemic voriconazole was utilized. The chest CT images and clinical symptoms of both patients markedly improved in the following third month. Instillation of AmB combined with systemic voriconazole may be a promising treatment option for NSCLC patients with CCPA who fail voriconazole monotherapy.

Etiologic characteristics revealed by mNGS-mediated ultra-early and early microbiological identification in airway secretions from lung transplant recipients.

Background: Post-operative etiological studies are critical for infection prevention in lung transplant recipients within the first year. In this study, mNGS combined with microbial culture was applied to reveal the etiological characteristics within one week (ultra-early) and one month (early) in lung transplant recipients, and the epidemiology of infection occurred within one month. Methods: In 38 lung transplant recipients, deep airway secretions were collected through bronchofiberscope within two hours after the operation and were subjected to microbial identification by mNGS and microbial culture. The etiologic characteristics of lung transplant recipients were explored. Within one month, the infection status of recipients was monitored. The microbial species detected by mNGS were compared with the etiological agents causing infection within one month. Results: The detection rate of mNGS in the 38 airway secretions specimens was significantly higher than that of the microbial culture (P<0.0001). MNGS identified 143 kinds of pathogenic microorganisms; bacterial pathogens account for more than half (72.73%), with gram-positive and -negative bacteria occupying large proportions. Fungi such as Candida are also frequently detected. 5 (50%) microbial species identified by microbial culture had multiple drug resistance (MDR). Within one month, 26 (68.42%) recipients got infected (with a median time of 9 days), among which 10 (38.46%) cases were infected within one week. In the infected recipients, causative agents were detected in advance by mNGS in 9 (34.62%) cases, and most of them (6, 66.67%) were infected within one week (ultra-early). In the infection that occurred after one week, the consistency between mNGS results and the etiological agents was decreased. Conclusion: Based on the mNGS-reported pathogens in airway secretions samples collected within two hours, the initial empirical anti-infection regimes covering the bacteria and fungi are reasonable. The existence of bacteria with MDR forecasts the high risk of infection within 48 hours after transplant, reminding us of the necessity to adjust the antimicrobial strategy. The predictive role of mNGS performed within two hours in etiological agents is time-limited, suggesting continuous pathogenic identification is needed after lung transplant.

[Effect of hypoxia on the expression and production of fractalkine in pulmonary artery smooth muscle cells and pulmonary microvascular endothelial cells].

OBJECTIVE: To investigate the effect of hypoxia on the expression and production of fractalkine (FKN) in cultured rat pulmonary artery smooth muscle cells (PASMCs) and pulmonary microvascular endothelial cells (PMVECs). METHODS: PASMCs and PMVECs from SD rat were cultured in vitro, and were exposed to hypoxia for 12 h,24 h and 48 h. The expressions of fractalkine mRNA and protein in PASMCs and PMVECs were measured by the methods of in situ hybridization and immunohistochemistry. The fractalkine concentrations in supernatant fluid of cultured PASMCs and PMVECs were measured by enzyme-linked immunosorbent assay. RESULTS: (1) Compared with the control group, the expression and production of fractalkine in PASMCs did not increase after the treatment of hypoxia for 12 hours (P > 0.05), but increased after being treated with hypoxia for 24 hours (P < 0.05), and became more significant after 48 hours (P < 0.01). (2) Compared with the control group, there were no differences of FKN concentrations in supernatant fluid of PMVECs, FKN mRNA and protein levels in PMVECs after being treated with hypoxia for 12 hours, 24 hours or 48 hours (P > 0.05). CONCLUSION: Hypoxia stimulates the synthesis and secretion of fractalkine in cultured rat PASMCs.