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1.
J Thorac Dis ; 16(6): 4016-4029, 2024 Jun 30.
Article in English | MEDLINE | ID: mdl-38983176

ABSTRACT

Background: Invasive fungal disease (IFD) has become a serious threat to human health in China and around the world, with high mortality and morbidity. Currently, the misdiagnosis rate of IFD is extremely high, compounded with the low quality of prescription antifungals and the high incidence of adverse events associated with IFD treatment, resulting in lengthy hospitalization, low clinical response, and high disease burden, which have become serious challenges in clinical practice. Antifungal stewardship (AFS) can not only significantly increase the early diagnosis rate of IFD, reduce inappropriate utilization of antifungal drugs, improve patient prognosis, but can also improve therapeutic safety and reduce healthcare expenses. Thus, it is urgent to identify key AFS metrics suitable for China's current situation. Methods: Based on metrics recommended by international AFS consensuses, combined with the current situation of China and the clinical experience of authoritative experts in various fields, several metrics were selected, and experts in the fields of respiratory diseases, hematology, intensive care units (ICUs), dermatology, infectious diseases, microbiology laboratory and pharmacy were invited to assess AFS metrics by the Delphi method. Consensus was considered to be reached with an agreement level of ≥80% for the metric. Results: Consensus was reached for 24 metrics, including right patient metrics (n=4), right time metrics (n=3), and right use metrics (n=17). Right use metrics were further subdivided into drug choice (n=8), drug dosage (n=4), drug de-escalation (n=1), drug duration (n=2), and drug consumption (n=2) metrics. Forty-six authoritative experts assessed and reviewed the above metrics, and a consensus was reached with a final agreement level of ≥80% for 22 metrics. Conclusions: This consensus is the first to propose a set of AFS metrics suitable for China, which helps to establish AFS standards in China and is also the first AFS consensus in Asia, and may improve the standard of clinical diagnosis and treatment of IFD, and guide hospitals to implement AFS, ultimately promoting the rational use of antifungal drugs and improving patient prognosis.

2.
EBioMedicine ; 96: 104790, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37708700

ABSTRACT

BACKGROUND: Severe community-acquired pneumonia (SCAP) results in high mortality as well as massive economic burden worldwide, yet limited knowledge of the bio-signatures related to prognosis has hindered the improvement of clinical outcomes. Pathogen, microbes and host are three vital elements in inflammations and infections. This study aims to discover the specific and sensitive biomarkers to predict outcomes of SCAP patients. METHODS: In this study, we applied a combined metagenomic and transcriptomic screening approach to clinical specimens gathered from 275 SCAP patients of a multicentre, prospective study. FINDINGS: We found that 30-day mortality might be independent of pathogen category or microbial diversity, while significant difference in host gene expression pattern presented between 30-day mortality group and the survival group. Twelve outcome-related clinical characteristics were identified in our study. The underlying host response was evaluated and enrichment of genes related to cell activation, immune modulation, inflammatory and metabolism were identified. Notably, omics data, clinical features and parameters were integrated to develop a model with six signatures for predicting 30-day mortality, showing an AUC of 0.953 (95% CI: 0.92-0.98). INTERPRETATION: In summary, our study linked clinical characteristics and underlying multi-omics bio-signatures to the differential outcomes of patients with SCAP. The establishment of a comprehensive predictive model will be helpful for future improvement of treatment strategies and prognosis with SCAP. FUNDING: National Natural Science Foundation of China (No. 82161138018), Shanghai Municipal Key Clinical Specialty (shslczdzk02202), Shanghai Top-Priority Clinical Key Disciplines Construction Project (2017ZZ02014), Shanghai Key Laboratory of Emergency Prevention, Diagnosis and Treatment of Respiratory Infectious Diseases (20dz2261100).

3.
Front Med (Lausanne) ; 10: 1107330, 2023.
Article in English | MEDLINE | ID: mdl-37484845

ABSTRACT

Introduction: Organ transplant recipients are at increased risk of developing pulmonary cryptococcosis (PC) due to weakened cell-mediated immunity caused by immunosuppressors. However, the nonspecific symptoms associated with PC can often lead to misdiagnosis and inappropriate treatment. Methods: We conducted a retrospective analysis of data from 23 kidney transplant recipients with PC between April 2006 to January 2021. Results: The median time from transplantation to the diagnosis of pathology-proven PC 4.09 years. Seventeen patients presented respiratory symptoms, including sputum-producing cough and dyspnea. Additionally, three patients also developed central nervous system (CNS) infections. Chest CT scans frequently revealed nodule-shaped lesions, which can mimic lung carcinoma. Serological tests did not demonstrate any specific changes. Nine patients received surgical resection as treatment. Fourteen patients were treated with antifungal medication only. No recurrence was observed in all 23 patients. Conclusion: Our study suggests that fever and sputum-producing cough are common symptoms of PC, and cryptococcal meningitis should not be excluded if corresponding symptoms occur. Fluconazole is a common and effective antifungal agent. Surgical resection should be considered for patients who do not respond well to antifungal therapy. Clinicians should be aware of these findings when evaluating transplant recipients with respiratory symptoms.

4.
Clin Respir J ; 17(5): 343-356, 2023 May.
Article in English | MEDLINE | ID: mdl-37094822

ABSTRACT

Acquired digestive-respiratory tract fistulas occur with abnormal communication between the respiratory tract and digestive tract caused by a variety of benign or malignant diseases, leading to the alimentary canal contents in the respiratory tract. Although various departments have been actively exploring advanced fistula closure techniques, including surgical methods and multimodal therapy, some of which have gotten good clinical effects, there are few large-scale evidence-based medical data to guide clinical diagnosis and treatment. The guidelines update the etiology, classification, pathogenesis, diagnosis, and management of acquired digestive-respiratory tract fistulas. It has been proved that the implantation of the respiratory and digestive stent is the most important and best treatment for acquired digestive-respiratory tract fistulas. The guidelines conduct an in-depth review of the current evidence and introduce in detail the selection of stents, implantation methods, postoperative management and efficacy evaluation.


Subject(s)
Digestive System Fistula , East Asian People , Respiratory Tract Fistula , Humans , Consensus , Respiratory System , Respiratory Tract Fistula/diagnosis , Respiratory Tract Fistula/etiology , Respiratory Tract Fistula/therapy , Stents/adverse effects , Treatment Outcome , Digestive System Fistula/diagnosis , Digestive System Fistula/etiology , Digestive System Fistula/therapy
6.
Emerg Microbes Infect ; 11(1): 556-566, 2022 Dec.
Article in English | MEDLINE | ID: mdl-35081880

ABSTRACT

Severe Community Acquired Pneumonia (SCAP) challenges public health globally. Considerable improvements in molecular pathogen testing emerged in the last few years. Our prospective study combinedly used traditional culture, antigen tests, PCR and mNGS in SCAP pathogen identification with clinical outcomes. From June 2018 to December 2019, we conducted a multi-centre prospective study in 17 hospitals of SCAP patients within 48 hours of emergency room stay or hospitalization in China. All clinical data were uploaded into an online database. Blood, urine and respiratory specimens were collected for routine culture, antigen detection, PCR and mNGS as designed appropriately. Aetiology confirmation was made by the local attending physician group and scientific committee according to microbiological results, clinical features, and response to the treatment. Two hundred seventy-five patients were included for final analysis. Combined detection methods made identification rate up to 74.2% (222/299), while 14.4% (43/299) when only using routine cultures and 40.8% (122/299) when not using mNGS. Influenza virus (23.2%, 46/198), S. pneumoniae (19.6%, 39/198), Enterobacteriaceae (14.6%, 29/198), Legionella pneumophila (12.6%, 25/198), Mycoplasma pneumoniae (11.1%, 22/198) were the top five common pathogens. The in-hospital mortality of patients with pathogen identified and unidentified was 21.7% (43/198) and 25.9% (20/77), respectively. In conclusion, early combined detection increased the pathogen identification rate and possibly benefitted survival. Influenza virus, S. pneumoniae, Enterobacteriaceae was the leading cause of SCAP in China, and there was a clear seasonal distribution pattern of influenza viruses. Physicians should be aware of the emergence of uncommon pathogens, including Chlamydia Psittaci and Leptospira.


Subject(s)
Chlamydophila psittaci , Community-Acquired Infections , Pneumonia, Bacterial , Psittacosis , Adult , Community-Acquired Infections/diagnosis , Community-Acquired Infections/epidemiology , Humans , Pneumonia, Bacterial/diagnosis , Pneumonia, Bacterial/epidemiology , Prospective Studies
7.
Sleep Breath ; 26(2): 559-566, 2022 06.
Article in English | MEDLINE | ID: mdl-34148174

ABSTRACT

PURPOSE: Prior reports have examined the relationship between obstructive sleep apnea (OSA) and the mortality rate of lung cancer. However, the findings remain controversial. The present meta-analysis was performed to assess the relationship between OSA and increased risk of mortality in patients with lung cancer. METHODS: PubMed, Web of Science, and Embase were systematically searched for the correlative studies. Data were analyzed and pooled to evaluate odds ratios (ORs) of lung cancer mortality related to OSA. RESULTS: From 249 identified studies, 3 met inclusion criteria and were analyzed, including 67 patients with lung cancer and comorbid OSA and 45 patients with lung cancer and no OSA. The meta-analysis indicated that OSA was not significantly correlated with mortality rate in lung cancer (OR = 2.005, 95% CI = 0.703 to 5.715, z = 1.30, p = 0.193). There was no significant publication bias according to Begg's tests (p = 0.296) and Egger's tests (p = 0.097). CONCLUSION: This meta-analysis suggests that OSA is not significantly correlated with the mortality rate in lung cancer.


Subject(s)
Lung Neoplasms , Sleep Apnea, Obstructive , Comorbidity , Humans , Odds Ratio , Sleep Apnea, Obstructive/complications , Sleep Apnea, Obstructive/epidemiology
8.
Curr Med Res Opin ; 37(4): 693-701, 2021 04.
Article in English | MEDLINE | ID: mdl-33534617

ABSTRACT

OBJECTIVES: To evaluate the efficacy and safety of oral sitafloxacin versus oral moxifloxacin in the treatment of Chinese adults with community-acquired pneumonia (CAP). PATIENTS AND METHODS: This is a multicenter, randomized, open-label, positive-controlled clinical trial (chinadrugtrials.org.cn identifier: CTR20130046). CAP patients received sitafloxacin tablets 100 mg once daily (qd) or 100 mg twice daily (bid) to compare with moxifloxacin tablets 400 mg qd, for 7-10 days. The primary outcome was non-inferiority of sitafloxacin to moxifloxacin in clinical cure rate at test of cure (TOC) visit in per-protocol set (PPS). RESULTS: A total of 343 patients were randomized (sitafloxacin 100 mg qd, n = 117; sitafloxacin 100 mg bid, n = 116; moxifloxacin, n = 110), 291 patients were included in the PPS (sitafloxacin 100 mg qd, n = 96; sitafloxacin 100 mg bid, n = 94; moxifloxacin, n = 101). The clinical cure rate was 94.8% in the sitafloxacin 100 mg qd group, 96.8% in the sitafloxacin 100 mg bid group and 95.0% in the moxifloxacin group. At the TOC visit, the microbiological success rate was 97.0% (32/33) in the sitafloxacin 100 mg qd group, 97.1% (34/35) in the sitafloxacin 100 mg bid group and 94.9% (37/39) in the moxifloxacin group in the microbiological evaluable set (MES). The incidence of study-drug-related adverse events (AEs) was 23.3% (27/116) in the sitafloxacin 100 mg qd group, 29.8% (34/114) in the sitafloxacin 100 mg bid group and 28.2% (31/110) in the moxifloxacin group (p > .05). The common AEs related to study drug were dizziness, nausea, diarrhea, increased platelet count and alanine transaminase (ALT) elevation. All the AEs resolved completely after discontinuation of study drug. CONCLUSION: Sitafloxacin 100 mg qd or 100 mg bid for 7-10 days is not inferior to moxifloxacin 400 mg qd for 7-10 days in clinical efficacy for adult CAP patients. Sitafloxacin provides a safety profile comparable to moxifloxacin.


Subject(s)
Anti-Bacterial Agents , Pneumonia , Adult , Anti-Bacterial Agents/adverse effects , Double-Blind Method , Fluoroquinolones/adverse effects , Humans , Moxifloxacin/adverse effects , Treatment Outcome
9.
J Cell Mol Med ; 25(5): 2609-2620, 2021 03.
Article in English | MEDLINE | ID: mdl-33565239

ABSTRACT

DNA methylation is important for lung cancer prognosis. In this work, it is aimed to seek novel biomarkers with DNA methylation-expression-pathway pattern and explore its underlying mechanism. Prognostic DNA methylation sites and mRNAs were screened in NSCLC data set from TCGA, and further validated using the samples retrospectively collected, and EXT1 was identified as a potential target. Gene body methylation of three CpG sites (cg03276982, cg11592677, cg16286281) on EXT1 was significantly associated with clinical outcome, and the EXT1 gene expression also predicted prognosis. The expression level of EXT1 was also correlated with its DNA methylation level. This observation was further validated in a new data set consist of 170 samples. Knocking down of EXT1 resulted in decreased proliferation and migration. EXT1 targets were analysed using GSEA. It is found that the WNT signalling is the potential downstream target of EXT1. Further analyses revealed that the EXT1 targets the beta-catenin and effect migration rate of NSCLC cell lines. The WNT signalling inhibitor, XAV-939, effectively disrupted the migration promotion effect induced by EXT1. In summary, EXT1 methylation regulates the gene expression, effects the proliferation and migration via WNT pathway and predicted a poor prognosis for NSCLC.


Subject(s)
Carcinoma, Non-Small-Cell Lung/genetics , Carcinoma, Non-Small-Cell Lung/metabolism , DNA Methylation , Gene Expression Regulation, Neoplastic , Lung Neoplasms/genetics , Lung Neoplasms/metabolism , N-Acetylglucosaminyltransferases/genetics , Wnt Signaling Pathway , Biomarkers, Tumor , Carcinoma, Non-Small-Cell Lung/mortality , Carcinoma, Non-Small-Cell Lung/pathology , Cell Line, Tumor , Cell Movement/genetics , Cell Proliferation , CpG Islands , Humans , Lung Neoplasms/mortality , Lung Neoplasms/pathology , Neoplasm Grading , Neoplasm Staging , Prognosis , Survival Analysis
10.
Ann Palliat Med ; 10(1): 759-766, 2021 Jan.
Article in English | MEDLINE | ID: mdl-33440949

ABSTRACT

Talaromyces marneffei (T. marneffei) is a pathogenic, thermally dimorphic fungus that can cause invasive infection and significant morbidity in immunocompromised patients, especially those with human immunodeficiency virus (HIV) or other immune defects. Currently, T. marneffei infection is understood to be not limited only to immunodeficient patients, as cases of immunocompromised patients or immunocompetent patients associated with T. marneffei infection have been increasingly reported in recent years. The exact mechanism is not yet clear. This study reports a case of an advanced lung adenocarcinoma patient with T. marneffei infection. The patient is a 59-year-old female with a 3-month history of coughing, expectoration, and progressive dyspnea. Computed tomography (CT) scans showed a mass in the left lower lung, multiple plaques and nodules in both lungs, and left pleural effusion. The patient was diagnosed with T. marneffei infection, as T. marneffei was found in both the bronchoalveolar lavage fluid (BALF) and the sputum. According to the pathology of the left lung lesion by transbronchial lung biopsy (TBLB) and contrast-enhanced brain magnetic resonance imaging (MRI), the patient was diagnosed with epidermal growth factor receptor (EGFR) mutation-positive stage Ⅳ lung adenocarcinoma (T4N3M1c). She received intravenous liposomal amphotericin B and oral itraconazole as anti-fungal treatments, meanwhile, icotinib was used as an anti-tumor treatment. Following treatment, CT re-examination showed that the mass was remarkably absorbed, and some of the lung nodules had disappeared. No relapse of T. marneffei infection was found during the follow-up. This case indicates that patients with malignant lung tumors may possibly become infected with T. marneffei. Sequential treatment of amphotericin liposome B followed by itraconazole is effective for lung cancer patients with T. marneffei infection.


Subject(s)
Adenocarcinoma of Lung , Lung Neoplasms , Pneumonia , Talaromyces , Adenocarcinoma of Lung/drug therapy , Adenocarcinoma of Lung/genetics , Antifungal Agents/therapeutic use , ErbB Receptors/genetics , Female , Humans , Lung , Lung Neoplasms/drug therapy , Lung Neoplasms/genetics , Middle Aged , Mutation , Mycoses , Pneumonia/drug therapy , Talaromyces/genetics
11.
J Thorac Dis ; 12(5): 1799-1810, 2020 May.
Article in English | MEDLINE | ID: mdl-32642085

ABSTRACT

Medical thoracoscopy is a commonly used endoscopic technique for the diagnosis and treatment of respiratory diseases. As an invasive technique, it is mainly used for pleural effusions and pleural diseases that cannot be diagnosed by non-invasive methods. It is also of great application in the diagnosis and treatment of certain other diseases. Any technical operation requires special skills. There must be a learning process for mastering these skills. Although internal thoracoscopic surgery is simple, especially for respiratory specialists who have undergone training for thoracentesis or closed drainage, there are discrepancies in thoracoscopic diagnosis and treatment in hospitals in China; furthermore, the surgical methods are not uniform, and some even lead to serious complications. Therefore, the thoracoscopic diagnostic and treatment technology in China needs to be standardized. The Respiratory Professional Committee of the Integrated Medical Branch of the Chinese Medical Doctor Association invited relevant Chinese experts to formulate this standard after several rounds of discussion.

12.
Respir Res ; 21(1): 173, 2020 Jul 07.
Article in English | MEDLINE | ID: mdl-32635916

ABSTRACT

BACKGROUND: The European Organization for Research and Treatment of Cancer/Mycoses Study Group (EORTC/MSG) criteria are widely used in the diagnosis of invasive pulmonary aspergillosis (IPA), but they only apply to immunocompromised patients. We here aimed to identify clinical characteristics helpful to the diagnosis of IPA in non-immunocompromised patients. METHODS: This is a multicenter retrospective study. Data were collected from adult patients with IPA admitted to 15 tertiary hospitals in China from 2010 to 2016. RESULTS: We included 254 patients in the study, of whom 66 (26.0%) were immunocompromised, and 188 (74.0%) were not. Airway-invasion-associated computed tomography (CT) signs including patchy exudation along the airway (67.6% vs. 45.5%, P = 0.001) and thickened airway wall (42.0% vs. 16.7%, P < 0.001) were more common in non-immunocompromised patients than in immunocompromised ones, and angio-invasive CT signs were more common in immunocompromised patients (55.3% vs.72.7%, P = 0.013). Typical angio-invasive CT signs were delayed in non-immunocompromised IPA patients, whereas airway-invasive signs appear earlier. Host immunocompromised condition was associated with ICU admission and/or intubation (OR 1.095; 95% CI 1.461-6.122; P = 0.003). Poor prognosis (35.5% vs. 21.1%, P = 0.005) was more common in immunocompromised patients. CONCLUSION: Airway-invasion-associated CT presentations at early stages of the disease are characteristic of IPA in non-immunocompromised hosts.


Subject(s)
Invasive Pulmonary Aspergillosis/diagnostic imaging , Lung/diagnostic imaging , Adult , Aged , Aged, 80 and over , China , Female , Humans , Immunocompromised Host , Male , Middle Aged , Retrospective Studies , Surveys and Questionnaires , Tomography, X-Ray Computed , Young Adult
13.
Int J Mol Med ; 45(4): 1213-1224, 2020 Apr.
Article in English | MEDLINE | ID: mdl-32124932

ABSTRACT

Lung cancer is the leading cause of cancer­associated mortality worldwide. Cisplatin (DDP) is a first­line chemotherapeutic drug for the treatment of lung cancer; however, the majority of patients develop resistance to DDP. P­glycoprotein (P­gp), also referred to as multidrug resistance (MDR) protein 1, is associated with an MDR phenotype, which results in failure of cancer chemotherapy; thus, identifying effective MDR pump inhibitors may improve the outcomes of patients who develop resistance to treatment. Hesperetin is a derivative of hesperidin, which is extracted from tangerine peel and exhibits multiple antitumor properties. In the present study, human lung adenocarcinoma A549 and A549/DDP cells were treated with different concentrations of hesperetin and DDP, respectively. Furthermore, rhodamine 123 efflux assays, Cell Counting Kit­8 assays, immunofluorescence, reverse transcription­quantitative PCR and western blot analysis were used to elucidate the mechanisms underlying the effects of hesperetin On A549/DDP cells. Additionally, a xenograft model of lung cancer in nude mice was established to explore the effects of hesperetin on A549/DDP cell growth in vivo. The results demonstrated that hesperetin sensitized A549/DDP cells to DDP. In vivo, hesperetin pretreatment significantly inhibited tumor growth. Mechanistically, hesperetin markedly decreased the expression of P­gp and increased the intracellular accumulation of the P­gp substrate, rhodamine 123, in A549/DDP cells. In addition, pretreatment of A549/DDP cells with hesperetin significantly inhibited nuclear factor (NF)­κB (p65) activity and its nuclear translocation. Taken together, the results of the present study suggest that hesperetin reversed P­gp­mediated MDR by decreasing P­gp expression in A549/DDP cells, which was associated with inhibition of the NF­κB signaling pathway. These findings may provide the basis for the use of hesperetin clinically to reverse MDR.


Subject(s)
Cisplatin/pharmacology , Drug Resistance, Neoplasm/drug effects , Hesperidin/pharmacology , Lung Neoplasms , Neoplasm Proteins/metabolism , Signal Transduction/drug effects , Transcription Factor RelA/metabolism , A549 Cells , ATP Binding Cassette Transporter, Subfamily B/metabolism , Animals , Humans , Lung Neoplasms/drug therapy , Lung Neoplasms/metabolism , Lung Neoplasms/pathology , Mice , Mice, Nude
14.
BMC Pulm Med ; 20(1): 65, 2020 Mar 17.
Article in English | MEDLINE | ID: mdl-32178660

ABSTRACT

BACKGROUND: Chlamydia psittaci pneumonia is a zoonotic infectious disease caused by Chlamydia psittaci. Diagnostic tools, including culture, serologic test and PCR-based methods, are available but prone to false negative results. CASE PRESENTATION: This report included five cases of Chlamydia psittaci pneumonia. Symptoms and signs common to all 5 cases included fever, coughing, generalized muscle ache, and most notably, inflammatory infiltration of the lungs upon chest CT and X-ray. Metagenomic next-generation sequencing (mNGS) revealed the presence of Chlamydia psittaci in biopsy lung tissue in 3 cases and bronchoalveolar lavage fluid in the remaining 2 cases. Three patients responded to doxycycline plus moxifloxacin; two patients responded to moxifloxacin alone. CONCLUSIONS: mNGS could be used to diagnose Chlamydia psittaci pneumonia.


Subject(s)
Chlamydophila psittaci/genetics , Chlamydophila psittaci/isolation & purification , High-Throughput Nucleotide Sequencing , Pneumonia, Bacterial/diagnosis , Psittacosis/diagnosis , Aged , Aged, 80 and over , Bronchoalveolar Lavage Fluid/microbiology , Female , Humans , Male , Middle Aged , Pneumonia, Bacterial/physiopathology , Psittacosis/physiopathology , Tomography, X-Ray Computed
15.
Thorac Cancer ; 11(1): 181-190, 2020 01.
Article in English | MEDLINE | ID: mdl-31760687

ABSTRACT

With the development of interventional pulmonology, photodynamic therapy (PDT) is gradually being used in the treatment of respiratory malignant tumors because of its low level of trauma, high specificity, and compatibility with traditional or common therapies. However, at present, the data of clinical evidence-based medicine for PDT applied in central airway tumors is very limited, and derives mainly from case reports or series of case studies which lack consensus on clinical diagnosis and treatment. In order to further disseminate China's experience, the Tumor Photodynamic Therapy Committee of China Anti-Cancer Association and the World Endoscopy Association-Respiratory Endoscopy Association invited experts from relevant fields to form an expert committee. After several rounds of discussion and revision by this committee, and following a vote, the consensus was formulated for reference by physicians in respiratory, oncology and other related disciplines to refer to the practice of tumor photodynamic therapy.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Photochemotherapy/methods , Practice Guidelines as Topic/standards , Respiratory Tract Neoplasms/drug therapy , Humans , Prognosis , Respiratory Tract Neoplasms/pathology
16.
Life Sci ; 239: 116879, 2019 Dec 15.
Article in English | MEDLINE | ID: mdl-31682849

ABSTRACT

Lung cancer is the largest cause of morbidity and mortality among tumor diseases. Traditional first-line chemotherapeutic drugs are frequently accompanied by serious side effects when used to treat tumors, thus, novel drugs with reduced toxic effects may improve a patients' quality of life. Icariin, an extract of herba epimedii, has been demonstrated to exhibit multiple antitumor effects with low toxicity. In the present study, cell cycle analysis, apoptosis assays, DAPI staining, CCK8 assays, xenograft tumor models, mitochondrial membrane potential analysis, western blotting and reverse transcription-quantitative PCR were performed to determine the molecular mechanism underlying icariin activity in the human lung adenocarcinoma cell lines, A549 and H1975. The results showed that icariin reduced proliferation of A549 and H1975 cells in a time- and dose-dependent manner in vitro to a greater degree than the control BEAS-2B cells, and this was associated with increased apoptosis, but not with cell cycle progression. In vivo experiments showed that icariin treatment significantly decreased proliferation of H1975 cells in a xenograft mouse model. Mechanistically, icariin activated the mitochondrial pathway by inhibiting the activation of the PI3K-Akt pathway-associated kinase, Akt, resulting in the activation of members of the caspase family of proteins, and thus inducing apoptosis of A549 cells. Taken together, the results revealed that icariin has anti-cancer properties in lung cancer in vitro and in vivo without any noticeable toxic effects on normal lung epithelial cells. Icariin in combination with conventional anti-cancer agents may be an effective therapeutic strategy for treatment of lung carcinoma.


Subject(s)
Adenocarcinoma of Lung/metabolism , Flavonoids/pharmacology , Mitochondria/drug effects , A549 Cells , Animals , Apoptosis/drug effects , Caspases/metabolism , Cell Cycle/drug effects , Cell Line, Tumor , Cell Proliferation/drug effects , Cell Survival/drug effects , China , Drugs, Chinese Herbal/pharmacology , Flavonoids/metabolism , Humans , Lung Neoplasms/pathology , Membrane Potential, Mitochondrial/drug effects , Mice , Mice, Nude , Phosphatidylinositol 3-Kinases/metabolism , Proto-Oncogene Proteins c-akt/metabolism , Signal Transduction/drug effects , Xenograft Model Antitumor Assays
18.
J Cell Biochem ; 120(10): 17602-17615, 2019 10.
Article in English | MEDLINE | ID: mdl-31237014

ABSTRACT

Chronic obstructive pulmonary disease (COPD) is a major global epidemic with increasing incidence worldwide. The pathogenesis of COPD is involved with mitochondrial autophagy. Recently, it has been reported that FUN14 domain containing 1 (FUNDC1) is a mediator of mitochondrial autophagy. Therefore, we hypothesized that FUNDC1 was involved in cigarette smoke (CS)-induced COPD progression by regulating mitochondrial autophagy. In vitro cigarette smoke extract (CSE)-treated human bronchial epithelial cell (hBEC) Beas-2B cell line and in vivo CS-induced COPD mouse models were developed, in which FUNDC1 expression was measured. Next, whether FUNDC1 interacted with dynamin-related protein 1 (DRP1) in COPD was investigated. The functional mechanism of FUNDC1 in COPD was evaluated through gain- or loss-of-function studies. Then, pulmonary function, mitochondrial transmembrane potential (MTP) and mucociliary clearance (MCC) were examined. Levels of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) and expression of autophagy-specific markers (light chain 3 [LC3] II, LC3 I, and Tom20) were measured. Finally, apoptosis and mitochondrial autophagy were assessed. FUNDC1 was highly expressed in CSE-treated hBECs and COPD mice. Meanwhile, FUNDC1 was proved to interact with DRP1 in CSE-treated cells. Moreover, in CSE-treated hBECs, silencing FUNDC1 was observed to reduce levels of IL-6 and TNF-α, and MTP but increase MCC, and inhibit CSE-induced mitochondrial autophagy and Beas-2B cell apoptosis, which was consistent with the trend in COPD mouse models. In addition, pulmonary function of COPD mouse models was increased in response to FUNDC1 silencing. Finally, silencing of DRP1 also inhibited mitochondrial autophagy and Beas-2B cell apoptosis. Collectively, FUNDC1 silencing could suppress the progression of COPD by inhibiting mitochondrial autophagy and hBEC apoptosis through interaction with DRP1, highlighting a potential therapeutic target for COPD treatment.


Subject(s)
Cigarette Smoking/adverse effects , Membrane Proteins/genetics , Mitochondria/genetics , Mitochondrial Proteins/genetics , Pulmonary Disease, Chronic Obstructive/genetics , Animals , Apoptosis/drug effects , Autophagy/drug effects , Autophagy/genetics , Bronchi/drug effects , Bronchi/metabolism , Bronchi/pathology , Cigarette Smoking/genetics , Gene Expression Regulation/drug effects , Humans , Lung/drug effects , Lung/metabolism , Lung/physiology , Membrane Proteins/antagonists & inhibitors , Mice , Mitochondria/drug effects , Mitochondrial Proteins/antagonists & inhibitors , Pulmonary Disease, Chronic Obstructive/chemically induced , Pulmonary Disease, Chronic Obstructive/pathology , Pulmonary Disease, Chronic Obstructive/therapy , Respiratory Mucosa/drug effects , Respiratory Mucosa/metabolism , Respiratory Mucosa/pathology , Nicotiana/chemistry
19.
Am J Transl Res ; 11(4): 2463-2469, 2019.
Article in English | MEDLINE | ID: mdl-31105853

ABSTRACT

Objective: The effects and enhancement of catalpol (CP) on specific immune therapy (SIT) were investigated with an established animal model associated with bronchial asthma. Materials and methods: A total of 50 adults BALB/c mice were randomly divided into five groups with 10 mice in each group. These groups are control group, model group, CP group, SIT group and CP/SIT joint group. The mice were sensitized and challenged with OVA and Bronchoalveolar lavage fluid (BALF) and peripheral blood were obtained, the cell counts and the levels of cytokines (IL-1, IL-4, IFN-γ) in BALF were detected using ELISA methods. Results: The total number of cells in BALF of the group treated with CP/SIT joint group was significantly lower than the other experimental groups. Furthermore the eosinophils of the mice were dramatically reduced comparing the other experimental groups, the cytokines IL-1 and IL-4 display the similar tendency, but the IFN-γ concentration for the experimental groups was higher than the model group. After the therapy using CP, SIT and a combination of CP and SIT, asthma-associated inflammation was inhibited, IL-4 level was decreased and IFN-γ level was increased. In addition, the expression of TLR-4 protein in peripheral blood was detected by Western Blot method. Conclusions: In summary, CP can enhance the treating effect of SIT and the joint treatment by CP/SIT might be a potential method for clinical treatment of asthma, the mechanism is related to the inhibition of TLR-4 signaling pathway.

20.
Respiration ; 97(5): 484-494, 2019.
Article in English | MEDLINE | ID: mdl-30970361

ABSTRACT

Malignant central airway stenosis refers to airway stenosis caused by primary or metastatic malignant tumors which may lead to different levels of dyspnea or asphyxia in patients. With the rapid development of interventional pulmonology, therapeutic bronchoscopy has become one of the main methods for the diagnosis and treatment of malignant central airway stenosis. However, the level of diagnosis and treatment of respiratory intervention techniques in China is uneven at present, the treatment methods are not uniform, the treatment effects vary greatly, and some treatments even lead to serious complications. The interventional treatment technology for malignant central airway stenosis in China needs to be standardized. Therefore, the relevant experts of the Beijing Health Promotion Association Respiratory and Oncology Intervention and Treatment Alliance have formulated this consensus after several rounds of full discussion.


Subject(s)
Ablation Techniques , Airway Obstruction , Bronchoscopy , Dissection , Lung Neoplasms , Ablation Techniques/instrumentation , Ablation Techniques/methods , Airway Obstruction/etiology , Airway Obstruction/therapy , Bronchoscopy/instrumentation , Bronchoscopy/methods , China , Dilatation/instrumentation , Dilatation/methods , Dissection/instrumentation , Dissection/methods , Humans , Lung Neoplasms/complications , Lung Neoplasms/pathology , Neoplasm Staging , Severity of Illness Index , Stents/classification , Time-to-Treatment
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