Obstructive sleep apnea and the risk of mortality in patients with lung cancer: a meta-analysis.

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.

EXT1 methylation promotes proliferation and migration and predicts the clinical outcome of non-small cell lung carcinoma via WNT signalling pathway.

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.

Airway-invasion-associated pulmonary computed tomography presentations characteristic of invasive pulmonary Aspergillosis in non-immunocompromised adults: a National Multicenter Retrospective Survey in China.

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.

The application of metagenomic next-generation sequencing in diagnosing Chlamydia psittaci pneumonia: a report of five cases.

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.

Silencing FUNDC1 alleviates chronic obstructive pulmonary disease by inhibiting mitochondrial autophagy and bronchial epithelium cell apoptosis under hypoxic environment.

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.

Interventional Bronchoscopy for the Treatment of Malignant Central Airway Stenosis: An Expert Recommendation for China.

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.

Astragaloside IV sensitizes non-small cell lung cancer cells to gefitinib potentially via regulation of SIRT6.

Astragaloside IV, the active component of Astragalus membranaceus, exhibits diverse biological roles including the anti-tumor activity. In this study, we evaluated the chemosensitive role of astragaloside IV in non-small cell lung cancer cells. Cell Counting Kit-8 analysis was performed to determine cell viability. Real-time polymerase chain reaction and western blot were used to measure the messenger RNA and protein expression. Results showed that astragaloside IV treatment could suppress the proliferation of non-small cell lung cancer cells. In addition, combined treatment with astragaloside IV remarkably enhanced the chemosensitivity to gefitinib in three non-small cell lung cancer cell lines including NCI-H1299, HCC827, and A549. Furthermore, compared with gefitinib-treated cells, the messenger RNA expression of SIRT6 was obviously increased in non-small cell lung cancer cells treated with gefitinib combined with astragaloside IV. In addition, downregulation of SIRT6 was accomplished using small interference RNA technology. As a result, SIRT6 inhibition abolished the sensitization role of astragaloside IV in non-small cell lung cancer cells. Taken together, these data demonstrated that astragaloside IV sensitized tumor cells to gefitinib via regulation of SIRT6, suggesting that astragaloside IV may serve as potential therapeutic approach for lung cancer.

[The efficacy and safety of moxifloxacin in the treatment of patients with acute exacerbation of chronic obstructive pulmonary disease].

OBJECTIVE: To compare the effectiveness and safety of moxifloxacin and cefoperazone-sulbactam therapy in acute exacerbation of chronic obstructive pulmonary disease (COPD). METHODS: This was a prospective, randomized, multicentre study conducted between December 2011 and December 2012 involving 21 hospitals in Fujian. A total of 202 patients with AECOPD requiring antibiotic therapy were enrolled. Of these patients randomized to either treatments, 102 patients [male 60, female 42, (69.8 ± 6.5) y] received moxifloxacin (400 mg qd) and 100 [male 56, female 44, (69.6 ± 6.7) y] received cefoperazone-sulbactam (3.0 q 8 h). Clinical effectiveness, bacterial eradication and drug safety were evaluated. RESULTS: The clinical effectiveness rate was 90.2% (92/102) in the moxifloxacin group and 88.0% (88/100) in the cefoperazone-sulbactam group. The bacterial eradication rate was 51.9% (14/27) and 48.3% (14/29) in the 2 groups respectively. The differences between groups were not statistically significant in terms of clinical and microbiological effectiveness (χ² = 0.251, χ² = 0.072, both P > 0.05). The length of hospital stay and antibiotic-days were shorter in the moxifloxacin group [(8.7 ± 2.4) vs (11.7 ± 3.0) d; (6.7 ± 2.2) vs (8.7 ± 2.3) d], the differences being significant between the 2 arms. (t = 6.360, t = 7.732, P < 0.05). Both drugs were well tolerated with no significant differences in numbers of drug-related adverse events (P > 0.05). CONCLUSIONS: Moxifloxacin was equivalent to cefoperazone-sulbactam therapy for clinical success, bacteriologic eradication and showed superiority over the control group in shortening the length of hospital stay and antibiotic-days. Additionally, the drug safety of moxifloxacin was good.

ATF3 and extracellular matrix-related genes associated with the process of chronic obstructive pulmonary.

INTRODUCTION: Chronic obstructive pulmonary disease (COPD) is a major public health problem worldwide and is proved to be the number three cause of death in globally. The objective of this study was to explore the molecular mechanism of the progression of COPD. METHODS: Using the GSE1650 affymetrix microarray data accessible from Gene Expression Omnibus database, we first identified the differentially expressed genes (DEGs) between 18 COPD samples and 12 normal samples, followed by the GO / KEGG pathway analysis and gene interaction networks analysis of the DEGs. Our study identified 134 DEGs which involved in regulation of immune response, vesicle transport system, growth regulator and extracellular matrix (ECM)-related pathways. RESULTS: Gene interaction networks analysis showed that the sub-network involved by activating transcription factor-3 (ATF3) was the most significant sub-network in gene interaction networks. Furthermore, the investigation of extracellular matrix-related genes showed that genes like collagen and insulin-like growth factor binding protein could clearly distinguish the COPD and normal control. CONCLUSIONS: The genes regulated by ATF3 transcriptional activator as well as ECM-related genes may play an important role in the process of COPD. Our study provides a comprehensive bioinformatics analysis of genes and pathways which may be involved in the progression of COPD.

[A clinical analysis of eight proven cases of pulmonary mucormycosis].

OBJECTIVE: To improve the understanding of pulmonary mucormycosis by analyzing the clinical manifestations, imaging features, diagnosis, treatment and prognosis of this disease. METHODS: The clinical data of eight patients diagnosed as pulmonary mucormycosis by histopathologic examination were retrospectively analyzed. RESULTS: Eight patients included six males and two females with age from 36 days to 66 years. Underlying conditions covered diabetes (n = 4), renal transplantation (n = 3), premature (n = 1) and long-term corticosteroid treatment in two cases. Imaging manifestations revealed multiple irregular lumps or nodules in three cases, multiple cavities with thick wall in three cases, diffuse lung infiltrate in one case and lung opacities in one case. The diagnoses of seven patients were confirmed by percutaneous needle lung biopsy and the remaining one was diagnosed with fiberoptic bronchoscopy biopsy. Surgery combined with amphotericin B liposome (60 mg/d for three weeks) was applied to one patient who was cured with no recurrence after a 22 month follow-up. Three cases were given amphotericin B liposome (a newborn with 7mg/d for 62 days, the other two 60 mg/d for 31 days and 70 mg/d for 71 days respectively). All had achieved marked response with follow up from 8 to 29 months, but one patient relapsed and died of recurrent lung mucormycosis. The other three patients were treated with itraconazole 400-200 mg/d from 21 days to 1 year with duration of follow up from 1 month to 20 months. One patient was not evaluable due to missing. Two patients relapsed and one died. CONCLUSION: Pulmonary mucormycosis is difficult to diagnose and treat with a high mortality. Percutaneous transthoracic lung biopsy is a useful diagnostic method. Amphotericin B liposome or itraconazole may be active against mucus. Early control of causes is essential to improve the prognosis and reduce the recurrence in patients with pulmonary mucormycosis.

Consensus for antifungal stewardship in China (2024 edition).

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.

1,25-Dihydroxyvitamin D(3) (1,25-(OH)(2)D(3)) attenuates airway remodeling in a murine model of chronic asthma.

OBJECTIVES: 1,25-Dihydroxyvitamin D(3) (1,25-(OH)(2)D(3)) has immune- and inflammation-modulating properties in asthma, but its possible effects on asthmatic airway remodeling remain uncertain. In this study, we investigated the effects of 1,25-(OH)(2)D(3) on airway remodeling in a murine model of chronic asthma and investigated its role in regulating nuclear factor-κB (NF-κB) activation. METHODS: BALB/c mice were sensitized to ovalbumin (OVA) and subsequently exposed to intranasal OVA challenges for 9 weeks. Some mice also received an intraperitoneal injection of 1,25-(OH)(2)D(3) at the time of challenge. At the end of the challenge period, mice were evaluated for chronic airway inflammation and airway remodeling. Nuclear translocation of NF-κB p65 in lung tissue was examined by Western blot. Inhibitor of NF-κB alpha (IκBα) expression was determined by real-time quantitative Reverse Transcription Polymerase Chain Reaction (RT-PCR) and Western blot. Phosphorylated IκBα protein expression was also determined by Western blot. RESULTS: 1,25-(OH)(2)D(3) treatment reduced OVA-induced chronic inflammation in lung tissue and attenuated established structural changes of the airways, including subepithelial collagen deposition, goblet cell hyperplasia, and increased airway smooth muscle mass. 1,25-(OH)(2)D(3) also inhibited the nuclear translocation of NF-κB p65 in lung tissue. Concurrently, 1,25-(OH)(2)D(3) induced increased IκBα protein levels via inducing increased IκBα mRNA levels and decreased IκBα phosphorylation. CONCLUSION: 1,25-(OH)(2)D(3) could attenuate asthmatic airway remodeling and its inhibition of NF-κB activation may underlie this protective effect.

Expression of connective tissue growth factor and bone morphogenetic protein-7 in Pseudomonas aeruginosa-induced chronic obstructive pulmonary disease in rats.

Repeated intratracheal injection of Pseudomonas aeruginosa (PA) in male Wistar rats was used to investigate the role of chronic infection in the development of chronic obstructive pulmonary disease (COPD) and the possible involvement of connective tissue growth factor (CTGF) and bone morphogenetic protein-7 (BMP-7) in this process. Injections of PA or normal saline solution were given for 8 weeks and the rats observed for a further 8 weeks. In addition to arterial blood gas, lung function and lung pathology measurement during this time period, protein and mRNA expression of CTGF and BMP-7 were measured, and the correlation of expression of CTGF and BMP-7 with pathological changes in the lung was evaluated. Repeated intratracheal PA infection in rats caused reduction in body weight, hypoxia, carbon dioxide retention, compromised lung function, chronic inflammation, thickening of the tracheal and arterial walls, and emphysema, changes consistent with those of COPD. Rats with PA infection also had increased CTGF and decreased BMP-7 expression, suggesting that both CTGF and BMP-7 are involved in the occurrence and development of airway remodeling. Our findings suggest that repeated airway infection is not only a factor resulting in deterioration of COPD, but is also a risk factor for its development, and that CTGF and BMP-7 are involved in the pathogenesis of this condition.

Comparison of different therapeutic approaches for pulmonary cryptococcosis in kidney transplant recipients: a 15-year retrospective analysis.

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.

A multicenter prospective study of comprehensive metagenomic and transcriptomic signatures for predicting outcomes of patients with severe community-acquired pneumonia.

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).

Chinese expert consensus on interventional diagnosis and management of acquired digestive-respiratory tract fistulas (second edition).

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.

Aetiology of severe community acquired pneumonia in adults identified by combined detection methods: a multi-centre prospective study in China.

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.

[Inhibition of 1,25-(OH)2D3 on passively sensitized human airway smooth muscle cells].

OBJECTIVE: To investigate the effects of 1,25-(OH)(2)D(3) on the proliferation of passively sensitized human airway smooth muscle cells (HASMCs) and their expressions of MMP-9 and a disintegrin and metalloprotease 33(ADAM33). METHODS: HASMCs were passively sensitized with 10% serum from asthmatic patients. MTT colorimetry assay was used to examine the effect of 1,25-(OH)(2)D(3) on cell proliferation at different concentrations (10(-10) mol/L, 10(-9) mol/L, 10(-8) mol/L, 10(-7) mol/L).By this way, its optimal inhibitory concentration was determined. And then the effects of 1,25-(OH)(2)D(3) at the optimal concentration on cell proliferation was examined by the same MTT assay and cell cycle analysis by flow cytometry. The expressions of MMP-9 and ADAM33 in HASMCs were studied by real-time quantitative RT-PCR and Western blotting analysis. RESULTS: (1) Inhibition of cell proliferation by 1,25-(OH)(2)D(3) was barely detectable at 10(-10) mol/L. But with the increasing concentration ranging from 10(-9) mol/L to 10(-7) mol/L, 1,25-(OH)(2)D(3) markedly inhibited the cell proliferation concentration-dependently and reached the maximum effect at the concentration of 10(-7) mol/L. Accordingly, 10(-7) mol/L was chosen as the optimal concentration of 1,25-(OH)(2)D(3) for the following study. (2) At the concentration of 10(-7) mol/L, 1,25-(OH)(2)D(3) inhibited the cell proliferation of passively sensitized HASMCs in a time-dependent manner and hampered the G(1)/S transition. (3) 1,25-(OH)(2)D(3) pretreatment attenuated the MMP-9 and ADAM33 protein levels in passively sensitized HASMCs by (63.4 ± 3.6)% and (50.9 ± 2.9)%, respectively (P < 0.01). (4) 1,25-(OH)(2)D(3) significantly inhibited the MMP-9 and ADAM33 mRNA levels in passively sensitized HASMCs by (52.2 ± 2.5)% and (67.8 ± 3.2)%, respectively (P < 0.01). CONCLUSION: 1,25-(OH)(2)D(3) has a direct inhibitory effect on passively sensitized HASMCs in vitro, including the inhibition of cell proliferation and the expressions of MMP-9 and ADAM33, which maybe associated with the beneficial role of 1,25-(OH)(2)D(3) in the prevention and therapy of asthmatic airway remodeling.

[An experimental study on the safety of intratracheal drug administration].

OBJECTIVE: To explore whether injury and repair occur in the trachea and the lung after intra-tracheal administration of different drugs. METHODS: Wistar rats were randomly divided into 5 groups, a normal group, a blank control (BC) group, a normal saline (NS) group, a lidocaine (LD) group and an amikacin (AK) group. For the latter 3 groups, normal saline, lidocaine and amikacin were injected into trachea by needle puncture. Scanning electron microscope was used to observe the ultra-structural changes of the epithelium, and the percentage of the area of damage (PAD) in tracheal mucosa was calculated. Moreover, pathological changes of the mucous membrane of bronchioles and alveolar epithelial cells were also examined, and the degree of lung pathology was semi-quantified. RESULTS: Two hours after the injection of the 3 drugs, derangement and edema of the cilia were evident by scanning electron microscopy. The PAD of the NS group, the LD group and the AK group were (94.2 ± 3.2)%, (93.1 ± 3.0)% and (95.5 ± 1.8)%, respectively; all being significantly higher than that of the BC group (1.3 ± 0.3)%. For the NS group and the LD group, the PAD decreased significantly after 24 h, which were (73.7 ± 7.8)% and (81.0 ± 4.6)% respectively, and returned to normal at 48 h and 96 h. While for the AK group, the damage began to improve at 72 h [PAD (62.1 ± 5.2)%], and recovered at 96 h. Airway epithelial derangement and cell edema in the alveoli and the bronchioles also occurred 2 h after drug injection, and inflammatory cell infiltration became evident at 24 h. At this time, the score of pathology was 1.80 ± 0.84, 2.60 ± 0.55 and 2.80 ± 0.45 for the NS group, the LD group and the AK group, respectively; all being higher than that of the BC group (0). These pathological changes recovered totally after 72 h for the NS and the LD groups, and 96 h for the AK group. CONCLUSIONS: Intra-tracheal administration of normal saline, lidocaine and amikacin in rats led to reversible airway mucosal and lung tissue damages.

[Pulmonary cryptococcosis: analysis of 38 cases].

OBJECTIVE: To investigate the clinical features, radiology, diagnosis and treatment of pulmonary cryptococcosis. METHODS: A total of 38 cases of pulmonary cryptococcosis, confirmed by pathological examinations at Fuzhou General Clinical Medical College, Fujian Medical University from March 2003 to February 2010, were retrospectively studied. RESULTS: All of the cases were community-acquired. The patients consisted of 29 males and 9 females, aged from 21 to 70 years. There were no underlying diseases in 29 cases. The CD(4) cell numbers were normal in 20 patients. Radiological study showed that the majority of the lesions (35 cases) were close to the pleura. Lower lungs were often involved (left 21 and right 23). Pulmonary nodules, either solitary nodules (11 cases) or multiple nodules (16 cases), were the most common CT finding. The lesions had a higher standardized uptake value (SUV) in 4 patients with a PET-CT scan. The lung specimens of 33 cases were obtained by CT guided transthoracic needle aspiration biopsy. The disease was cured in 34 cases, and improved in 3 cases, but 1 died. CONCLUSIONS: Pulmonary cryptococcosis must be considered in the differential diagnosis of lesions of the lungs. The disease has some characteristics on radiology, such as multiple lesions, always close to the pleura and occurs frequently in the lower lungs. CT guided percutaneous biopsy is a safe and effective method for diagnosis.