The management pattern and outcomes of chronic thromboembolic pulmonary hypertension: rationale and design for a Chinese real-world study.

BACKGROUND: Chronic thromboembolic pulmonary hypertension (CTEPH) is a progressive pulmonary vascular disorder with substantial morbidity and mortality, also a disease underdiagnosed and undertreated. It is potentially curable by pulmonary endarterectomy (PEA) in patients with surgically accessible thrombi. Balloon pulmonary angioplasty (BPA) and targeted medical therapy are options for patients with distal lesions or persistent/recurrent pulmonary hypertension after PEA. There is an urgent need to increase the awareness of CTEPH. Qualified CTEPH centers are still quite limited. Baseline characteristics, management pattern and clinical outcome of CTEPH in China needs to be reported. METHODS AND DESIGN: The CHinese reAl-world study to iNvestigate the manaGEment pattern and outcomes of chronic thromboembolic pulmonary hypertension (CHANGE) study is designed to provide the multimodality treatment pattern and clinical outcomes of CTEPH in China. Consecutive patients who are ≥ 14 year-old and diagnosed with CTEPH are enrolled. The diagnosis of CTEPH is confirmed in right heart catheterization and imaging examinations. The multimodality therapeutic strategy, which consists of PEA, BPA and targeted medical therapy, is made by a multidisciplinary team. The blood sample and tissue from PEA are stored in the central biobank for further research. The patients receive regular follow-up every 3 or 6 months for at least 3 years. The primary outcomes include all-cause mortality and changes in functional and hemodynamic parameters from baseline. The secondary outcomes include the proportion of patients experiencing lung transplantation, the proportion of patients experiencing heart and lung transplantation, and changes in health-related quality of life. Up to 31 December 2023, the study has enrolled 1500 eligible patients from 18 expert centers. CONCLUSIONS: As a real-world study, the CHANGE study is expected to increase our understanding of CTEPH, and to fill the gap between guidelines and the clinical practice in the diagnosis, assessment and treatment of patients with CTEPH. REGISTRATION NUMBER IN CLINICALTRIALS.GOV: NCT05311072.

Corrigendum: Time to clinical improvement: an appropriate surrogate endpoint for pulmonary arterial hypertension medication trials.

[This corrects the article DOI: 10.3389/fcvm.2023.1142721.].

Combined allergic bronchopulmonary mycosis and eosinophilic granulomatosis with polyangiitis: A case report and literature review.

A 27-year-old female visited our hospital with a history of asthma, peripheral blood eosinophilia, increased total IgE, Aspergillus fumigatus specific IgE, reversible mild bronchiectasis, sinusitis, bronchial mucus plugs and cultivation of Aspergillus from BALF. Glucocorticoids therapy is effective. These results met the diagnostic criteria for both allergic bronchopulmonary aspergillosis (ABPM) and eosinophilic granulomatosis with polyangiitis (EGPA). Special attention should be paid to the possibility of both diseases coexisting in the disease process.

Time to clinical improvement: an appropriate surrogate endpoint for pulmonary arterial hypertension medication trials.

Background: Many retrospective studies suggest that risk improvement may be a suitable efficacy surrogate endpoint for pulmonary arterial hypertension (PAH) medication trials. This prospective multicenter study assessed the efficacy of domestic ambrisentan in Chinese PAH patients and observed risk improvement and time to clinical improvement (TTCI) under ambrisentan treatment. Methods: Eligible patients with PAH were enrolled for a 24-week treatment with ambrisentan. The primary efficacy endpoint was 6-min walk distance (Δ6MWD). The exploratory endpoints were risk improvement and TTCI, defined as the time from initiation of treatment to the first occurrence of risk improvement. Results: A total of 83 subjects were enrolled. After ambrisentan treatment, Δ6MWD was significantly increased at week 12 (42.2 m, P < 0.0001) and week 24 (53.4 m, P < 0.0001). Within 24 weeks, risk improvement was observed in 53 (64.6%) subjects (P < 0.0001), which is higher than WHO-FC (30.5%) and TAPSE/PASP (32.9%). Kaplan-Meier analysis of TTCI showed a median improvement time of 131 days and a cumulative improvement rate of 75.1%. Also, TTCI is consistent across different baseline risk status populations (log-rank P = 0.51). The naive group had more risk improvement (P = 0.043) and shorter TTCI (log-rank P = 0.008) than the add-on group, while Δ6MWD did not show significant differences between the two groups. Conclusions: Domestic ambrisentan significantly improved the exercise capacity and risk status of Chinese PAH patients. TTCI has a relatively high positive event rate within 24-week treatment duration. Compared to Δ6MWD, TTCI is not affected by baseline risk status. Additionally, TTCI could identify better improvements in patients, which Δ6MWD does not detect. TTCI is an appropriate composite surrogate endpoint for PAH medication trials. Clinical Trial Registration: NCT No. [ClinicalTrials.gov], identifier [NCT05437224].

Comparison of operation time, efficacy and safety between through-the-scope stent and over-the-while stent in malignant central airway obstruction: a multi-center randomized control trial.

Background: Self-expandable metallic (SEM) airway stents are an important approach to treating malignant central airway obstruction (CAO). Standard over-the-while (OTW) stent needs the guidance of a guide-wire. It should be implanted under flouroscopy or the guidance of bronchoscope visualization. In this study, we evaluated the operation time and safety between OTW stent and a novel through-the-scope (TTS) SEM airway stent. Methods: In this multi-center, randomized, parallel-group superiority study, malignant CAO patients were enrolled randomly assigned (2:1) to the TTS stent implantation group (TTS group) or the standard OTW stent group (OTW group) in six sites across China. The entire process of all surgical procedures was recorded by video. Primary endpoint was the operation time of the airway stent implantation and secondary endpoint was the success rate of the stent implantation as well as its efficacy and safety. Results: From May 15, 2017, to December 30, 2018, 148 patients were enrolled from the six sites. We analyzed 134 patients (including 91 patients from the TTS group and 43 patients from the OTW group) according to the per-protocol set. There were no significant differences in the ages, genders, underlying diseases, and stenosis sites between the two groups. The operation time in the TTS group was significantly shorter than that in the OTW group (104±68 vs. 252±111 seconds, P<0.001). Compared to the OTW group, the efficacy of stent implantation (97.80% vs. 90.70%, P=0.093) and rate of first-time successful stent implantation (78.02% vs. 74.42%, P=0.668) were higher in the TTS group, but did not reach statistically significance. The rates of granulation (28.57% vs. 41.86%, P=0.128) and restenosis (15.38% vs. 30.23%, P=0.064) in the TTS group were slightly lower as compared with the OTW group without achieving statistical significance. Conclusions: The TTS stent implantation procedure time was significantly shorter than that of the OTW airway stent with similar efficacy and complications, which might reduce the risk and flexibility of stent implantation. Trial Registration: Chinese Clinical Trial Registry ChiCTR-IOR-17011431.

Risk prediction in medically treated chronic thromboembolic pulmonary hypertension.

BACKGROUND: At present, there is no generally accepted comprehensive prognostic risk prediction model for medically treated chronic thromboembolic pulmonary hypertension (CTEPH) patients. METHODS: Consecutive medically treated CTEPH patients were enrolled in a national multicenter prospective registry study from August 2009 to July 2018. A multivariable Cox proportional hazards model was utilized to derive the prognostic model, and a simplified risk score was created thereafter. Model performance was evaluated in terms of discrimination and calibration, and compared to the Swedish/COMPERA risk stratification method. Internal and external validation were conducted to validate the model performance. RESULTS: A total of 432 patients were enrolled. During a median follow-up time of 38.73 months (IQR: 20.79, 66.10), 94 patients (21.8%) died. The 1-, 3-, and 5-year survival estimates were 95.5%, 83.7%, and 70.9%, respectively. The final model included the following variables: the Swedish/COMPERA risk stratum (low-, intermediate- or high-risk stratum), pulmonary vascular resistance (PVR, ≤ or > 1600 dyn·s/cm5), total bilirubin (TBIL, ≤ or > 38 µmol/L) and chronic kidney disease (CKD, no or yes). Compared with the Swedish/COMPERA risk stratification method alone, both the derived model [C-index: 0.715; net reclassification improvement (NRI): 0.300; integrated discriminatory index (IDI): 0.095] and the risk score (C-index: 0.713; NRI: 0.300; IDI: 0.093) showed improved discriminatory power. The performance was validated in a validation cohort of 84 patients (C-index = 0.707 for the model and 0.721 for the risk score). CONCLUSIONS: A novel risk stratification strategy can serve as a useful tool for determining prognosis and guide management for medically treated CTEPH patients. TRIAL REGISTRATION: ClinicalTrials.gov (Identifier: NCT01417338).

Endoplasmic reticulum stress/XBP1 promotes airway mucin secretion under the influence of neutrophil elastase.

Endoplasmic reticulum (ER) stress is an important reaction of airway epithelial cells in response to various stimuli, and may also be involved in the mucin secretion process. In the present study, the effect of ER stress on neutrophil elastase (NE)­induced mucin (MUC)5AC production in human airway epithelial cells was explored. 16HBE14o­airway epithelial cells were cultured and pre­treated with the reactive oxygen species (ROS) inhibitor, N­acetylcysteine (NAC), or the ER stress chemical inhibitor, 4­phenylbutyric acid (4­PBA), or the cells were transfected with inositol­requiring kinase 1α (IRE1α) small interfering RNA (siRNA) or X­box­binding protein 1 (XBP1) siRNA, respectively, and subsequently incubated with NE. The results obtained revealed that NE increased ROS production in the 16HBE14o­cells, with marked increases in the levels of ER stress­associated proteins, such as glucose­regulated protein 78 (GRP78), activating transcription factor 6 (ATF6), phosphorylated protein kinase R­like endoplasmic reticulum kinase (pPERK) and phosphorylated (p)IRE1α. The protein and mRNA levels of spliced XBP1 were also increased, and the level of MUC5AC protein was notably increased. The ROS scavenger NAC and ER stress inhibitor 4­PBA were found to reduce ER stress­associated protein expression and MUC5AC production and secretion. Further analyses revealed that MUC5AC secretion was also attenuated by IRE1α and XBP1 siRNAs, accompanied by a decreased mRNA expression of spliced XBP1. Taken together, these results demonstrate that NE induces ER stress by promoting ROS production in 16HBE14o­airway epithelial cells, leading to increases in MUC5AC protein production and secretion via the IRE1α and XBP1 signaling pathways.

Characteristics and long-term survival of patients with chronic thromboembolic pulmonary hypertension in China.

BACKGROUND AND OBJECTIVE: The purpose of this study was to report the characteristics and long-term survival of patients with CTEPH treated in three distinct ways: PEA, BPA and medical therapy. METHODS: Patients diagnosed with CTEPH were included in the registry that was set up in 18 centres from August 2009 to July 2018. The characteristics and survival of patients with CTEPH receiving the different treatments were reported. Prognostic factors were evaluated by Cox regression model. RESULTS: A total of 593 patients with CTEPH were included. Eighty-one patients were treated with PEA, 61 with BPA and 451 with drugs. The estimated survival rates at 1, 3, 5 and 8 years were, respectively, 95.2%, 84.6%, 73.4% and 66.6% in all patients; 92.6%, 89.6%, 87.5% and 80.2% in surgical patients; and 95.4%, 88.3%, 71.0% and 64.1% in medically treated patients. The estimated survival rates at 1, 3, 5 and 7 years in patients treated with BPA were 96.7%, 88.1%, 70.0% and 70.0%, respectively. For all patients, PEA was an independent predictor of survival. Other independent risk factors were CHD, cardiac index, PVR, big endothelin-1, APE and 6MWD. CONCLUSION: This is the first multicentre prospective registry reporting baseline characteristics and estimated survival of patients with CTEPH in China. The long-term survival rates are similar to those of patients in the international and Spanish registries. PEA is an independent predictor of survival.

Solitary fibrous tumor of the pleura in a 22-year-old woman: a case report.

Solitary fibrous tumor of the pleura (SFTP) is a rare disease, and most published case reports are in patients over 40 years old. We report a case of SFTP in a 22-year-old woman. The imaging features were observed using contrast-enhanced computed tomography (CT), and histomorphological features were evaluated using pathology and immunohistochemistry. The CT showed a mass in the pleura inside the ninth rib on the left. Pathological results of percutaneous puncture in the chest suggested the possibility of solitary fibroma. The patient underwent surgical resection, and the tumor measured 2.5 × 1.5 × 1.5 cm with an intact capsule. Pathological examination revealed a spindle cell tumor, and immunohistochemistry showed strong positive staining for CD34 and STAT6, consistent with typical solitary fibroma. Although SFTP is rare in young patients, early diagnosis and intervention are needed to avoid the possibility of future complications.

Circular RNA circABCC4 regulates lung adenocarcinoma progression via miR-3186-3p/TNRC6B axis.

Lung adenocarcinoma (LUAD), a general kind of bronchogenic malignancy globally, is depicted as one of the most critical factors affecting human health severely. Featured with loop structure, circular RNA (circRNA) has been described as an essential regulator of multiple human malignancies. Nevertheless, knowledge concerning the regulatory function of circRNA in LUAD progression remains limited. Identified as a novel circRNA, circABCC4 has not been studied in LUAD as yet. This is the first time to probe into the underlying role of circABCC4 in LUAD. In this study, a notably elevated expression of circABCC4 was found in LUAD tissues and cells. Besides, circABCC4 is verified to be characterized with a circular structure in LUAD. Functional assays elucidated that knockdown of circABCC4 significantly impaired LUAD cell proliferation, migration as well as accelerated cell apoptosis. Molecular mechanism experiments later revealed that circABCC4 could bind with miR-3186-3p and miR-3186-3p was a tumor suppressor in LUAD. Moreover, TNRC6B was validated to combine with miR-3186-3p, and its expression was respectively negatively and positively regulated by miR-3186-3p and circABCC4 in LUAD. Final rescue experiments further delineated that TNRC6B upregulation partially restored circABCC4 downregulation-mediated effect on LUAD progression. In sum, circABCC4 regulates LUAD progression via miR-3186-3p/TNRC6B axis.

Increased serum IL-17 and decreased serum IL-10 and IL-35 levels correlate with the progression of COPD.

Purpose: This study aimed to measure the serum levels of interleukin (IL)-17, IL-10, and IL-35 in patients with stable chronic obstructive pulmonary disease (COPD) and disclose the correlations between their expression levels and clinical factors of patients. Methods: A total of 75 patients with stable COPD (47 males and 28 females) and 30 healthy controls (15 males and 15 females) were included in this study. The serum levels of IL-17, IL-10, and IL-35 were determined by enzyme-linked immunosorbent assay. The correlations between their expression levels and clinical factors of patients were determined using linear regression methods. Results: The serum level of IL-17 was upregulated in stable COPD, and increased IL-17 expression was positively correlated with the Global Initiative for Chronic Obstructive Lung Disease (GOLD) grading, modified Medical Research Council (mMRC) score, and long clinical history (P<0.05), but negatively correlated with the pulmonary function (P<0.05) of patients. The serum levels of IL-10 and IL-35 were downregulated in stable COPD, and decreased IL-10 and IL-35 levels negatively correlated with the smoking status, GOLD grading, mMRC score, and long clinical history (P<0.05), but positively correlated with the pulmonary function (P<0.05) of patients. Moreover, the level of IL-17 negatively correlated with IL-10 and IL-35, but IL-10 positively correlated with IL-35. Conclusion: The serum levels of IL-17, IL-10, and IL-35 correlated with the clinical factors of COPD, indicating that they can serve as indicators to estimate the progression of COPD.

Factors associating with the presence of residual thrombosis after 3-month treatment of acute pulmonary embolism.

The present study aimed to investigate the factors associating with the presence of residual thrombosis in patients with acute pulmonary embolism (APE) after at least 3-month anticoagulant therapy. Demographic and clinical data of 180 cases in the affiliated hospital of Qingdao University from January 2005 to June 2015 were retrospectively analyzed. APE in all patients were confirmed by computed tomography pulmonary angiography (CTPA). Patients were then detected for the presence of residual thrombosis according to a second CTPA. After appropriate comparison test, multivariate logistic regression analysis was performed to identify predictors for residual thrombosis. Among 180 patients, complete clearance of thrombosis occurred in 115 (63.9%) patients. Residual thrombosis remained in 65 (36.1%) patients. The independent factors associating with residual thrombosis include unprovoked APE (OR 0.231, 95% CI 0.062-0.861) and fibrinogen level in acute phase (OR 1.958, 95% CI 1.282-2.911). Furthermore, these two variables were both associated with the presence of residual thrombosis in patients receiving different parenteral anticoagulants (unfractionated heparin or low-molecular-weight heparin). Pulmonary thrombosis in some patients with APE are not completely dissolved after at least 3-month treatment. Additionally, unprovoked APE is positive predictor of decreased residual thrombosis and fibrinogen level in acute phase is a risk factor of the presence of residual thrombosis.

The association of genetic polymorphisms of hypoxia inducible factor-1 alpha and vascular endothelial growth factor with increased risk of chronic obstructive pulmonary disease: A case-control study.

Accumulated data over the years have suggested that hypoxia inducible factor-1 alpha (HIF-1α) and its downstream vascular endothelial growth factor (VEGF) gene may be linked with chronic obstructive pulmonary disease (COPD). This study aims to investigate the association of HIF-1α and VEGF genetic polymorphisms and their correlated risks with COPD. COPD patients (case group) and healthy individuals (control group) were recruited. DNA was extracted to detect HIF-1α and VEGF genetic polymorphisms. Basal lung volume and forced expiratory capacity in 1st second (FEV1)/forced vital capacity (FVC) and FEV1/predicted value (pred)% were calculated. Genotype and allele distributions in HIF-1α and VEGF genes were analyzed. Kaplan-Meier curves and logistic regression model were used for analysis of survival and COPD risk factors. Haplotypes for HIF-1α rs11549465 and rs11549467 were analyzed. FEV1/FVC and FEV1/pred% in the case group were lower than the control group. Frequencies of HIF-1α rs11549465 CT + TT genotype and T allele, and rs11549467 GA + AA genotype and A allele were higher in the case group than the control group. Patients with rs11549465 CT + TT had higher COPD risk than those with the CC genotype. Patients with rs11549467 GA + AA showed higher COPD risk and lower FEV1/FVC and FEV1/pred% than those with the GG genotype. Patients with HIF-1α TA haplotype showed higher COPD risk than those with the CG haplotype. Survival rate of patients with HIF-1α rs11549467 GG genotype was higher than those with the GA + AA genotype. HIF-1α rs11549467 polymorphism may be associated with COPD risk.

Erlotinib induces the human non-small-cell lung cancer cells apoptosis via activating ROS-dependent JNK pathways.

Although erlotinib (ERL) has drawn more and more attention toward its anticancer properties effect, the underlying mechanisms of ERL's anticancer properties effect remain unclear yet. So, the aim of this research was to explore the underlying anticancer mechanisms of ERL and to explore whether the reactive oxygen species (ROS)-dependent c-Jun N-terminal kinase (JNK) pathway contributed to the anticancer properties provided by ERL. In our study, we used MTT assay to detect the anticell growth ability of ERL on human non-small-cell lung cancer cell lines (A549). The extent of cell apoptosis was determined by Hoechst 33342 staining and fluorescence-activated cell sorter (FACS) assay. Then, DCFH-DA and JC-1 staining were used to monitor intracellular reactive oxygen species (ROS) and mitochondrial membrane potential (MMP), respectively. Finally, the effect of ERL on phosphorylation state of JNK protein and downstream apoptosis concerned proteins were detected by western blotting assay. Results showed that ERL significantly suppressed the growth and reproduction of A549 cells with the concentration rising up in vitro. Hoechst 33342 staining and FACS assay also confirmed the proapoptosis effect of ERL on A549 cells with the concentration rising up. Furthermore, exposure of A549 cells to ERL increased the intracellular ROS production. As expected, intracellular ROS activated the proapoptotic JNK signaling pathway and inhibited the activation of EFGR signaling pathway. Our results also revealed that ERL could induce cell-cycle arrest at G0/G1 period. Activation of JNK protein decreased MMP and downregulated content of antiapoptotic protein Bcl-2 concomitant with the upregulated content of proapoptotic protein Bax in A549 cells. In addition, c-Jun and cleaved caspase-3 were also activated by the phosphorylated JNK induced by ERL. All of these proapoptosis effect of ERL was reversed by administration of N-acetylcysteine (NAC), which performed as a ROS scavenger. Our results suggest that ERL induces A549 cells apoptosis via activating ROS-dependent JNK pathways in human non-small lung cancer cells that provide a new experimental foundation for cancer therapy.

Caveolin-1 Promotes the Imbalance of Th17/Treg in Patients with Chronic Obstructive Pulmonary Disease.

The imbalance of Th17/Treg cells plays an important role in the pathogenesis of chronic obstructive pulmonary disease (COPD). Caveolin-1 (Cav-1) has been regarded as a potential critical regulatory protein in pathological mechanisms of chronic inflammatory respiratory diseases. Therefore, we investigated whether the loss of Cav-1 is involved in the homeostasis of Th17/Treg cells in COPD. We examined the expressions of plasma Cav-1 and circulating Th17, Treg cells, and the related cytokines in patients with COPD. Enzyme-linked immunosorbent assay (ELISA) analyses showed a significant reduction of plasma Cav-1 levels in patients with stable COPD (SCOPD) and acutely exacerbated COPD (AECOPD) compared to smokers without COPD. This loss was associated with an increase in frequency of Treg and decreased in frequency of Th17 cells. To further identify the role of Cav-1, we studied the effects of Cav-1 overexpression or downregulation on frequencies of Treg and Th17 cells in peripheral blood mononuclear cells (PBMCs) from subjects. Interestingly, small interfering RNA (siRNA) downregulation of Cav-1 was accompanied by an augmentation of Treg and reduction of Th17 expression. Together, our study demonstrated that the loss of Cav-1 contributed to the imbalance of Th17/Treg cells in patients with COPD.

Inverse relationship of bleeding risk with clot burden during pulmonary embolism treatment with LMW heparin.

INTRODUCTION: Clinically relevant bleeding occurs three times as frequently as recurrent venous thromboembolism in the modern early treatment of pulmonary embolism (PE) with fixed-dose, unmonitored anticoagulants. Unfractionated heparin (UFH) is monitored and adjusted to assure efficacy and minimize bleeding risk, but low molecular weight heparin (LMWH) is not. PE requires more anticoagulant than isolated deep venous thrombosis. Speculating that PE with low clot burden could lead to excess bleeding with unadjusted LMWH treatment but not with UFH, we compared PE patients receiving either UFH or LMWH with high and low clot burden for clinically significant bleeding in an observational study. MATERIALS AND METHODS: Patients with acute PE at multiple Chinese teaching hospitals had been randomized to UFH or LMWH for initial treatment. These treatment cohorts had baseline measurement of pulmonary artery obstruction (PAO) score, which was prospectively separated into quartiles, lowest to highest PAO. All patients were followed for bleeding episodes, which were subsequently analyzed by quartile of PAO. RESULTS: Two hundred seventy-four patients divided between the two groups had similar efficacy and safety outcomes (12 clinically significant bleeds in the UFH group vs 15 in the LMWH group). LMWH recipients with the smallest clot burdens (lowest PAO quartiles) had highest bleeding rates (Cochran-Armitage trend test, P trend = 0.048), but there was no such trend for UFH recipients. CONCLUSIONS: For UFH, excess anticoagulant pro-hemorrhagic potential is down-adjusted via activated partial thromboplastin time monitoring, but for LMWH it is not. For PE patients at high bleeding risk, UFH may be safer if the clot burden is small.

Thoracoscopic tracheal resection and reconstruction for adenoid cystic carcinoma.

We describe a novel technique of thoracoscopic circumferential tracheal resection and end-to-end anastomosis. A 60-year-old woman presented with wheezing and progressive dyspnea. Computed tomography scan revealed a mass at the lower trachea, and a nitinol mesh stent was implanted by bronchoscopy. After 2 weeks, a complete thoracoscopic tracheal resection and reconstruction was performed. The postoperative course was uneventful. The final pathologic examination confirmed the diagnosis of primary adenoid cystic carcinoma of the trachea.

Expression of high mobility group box - B1 (HMGB-1) and matrix metalloproteinase-9 (MMP-9) in non-small cell lung cancer (NSCLC).

OBJECTIVE: This study evaluated the expression level of high mobility group box-B1 (HMGB-1) and matrix metalloproteinase-9 (MMP-9) in non-small cell lung cancer (NSCLC) inmorder to reveal any relation with development and prognosis. METHODS: NSCLC and normal tissues were selected from 30 patients at age of 30- 73, and used for RT-PCR and Western blot analyses of HMGB-1. A total of 100 paraffin embedded NSCLC tissues were also isolated from patients through surgical resection, and used for detection of HMGB-1 by immunohistochemistry. In addition, 50 samples were also applied for MMP-9 detection, and 30 normal tissues were considered as controls. Correlation analysis of HMGB-1 and MMP-9 was carried out by Pearsons correlation coefficient. RESULTS: The average expression level of HMGB-1 in NSCLC patients was significantly higher than in normal lung tissues. In addition, patients in III-IV period exhibit significantly higher positive rate of HMGB- 1 when compared with I-II period cases. Furthermore, a positive correlation with HMGB-1 was found in the expression of MPP-9. CONCLUSION: HMGB-1 was highly expressed in NSCLC, which may become a prognostic and predictive marker for NSCLC. Besides, MPP-9 was positively correlated with HMGB-1.

Optimal time to use low molecular weight heparin on prethrombotic state of rat chronic obstructive pulmonary disease model.

BACKGROUND: Low molecular weight heparin (LMWH), as one of anticoagulant drugs, has been used for the treatment of chronic obstructive pulmonary disease (COPD) with prethrombotic state, but the specific use time is unclear. The aim of the study is to observe the effect of LMWH at two different periods of prethrombotic state in COPD in rats and to find the optimal time to use LMWH. METHODS: Forty Wistar rats were randomly divided into 4 groups: normal control, raised for 55 days without any treatment; COPD control without LMWH, cigarette inhalation plus intratracheal instillation of lipopolysaccharide and hypodermic injection of normal saline once a day for 10 days; COPD control given LMWH 150 U/kg subcutaneous injection, once a day for 10 days starting day 15 (LMWH-d15); COPD control given LMWH 150 U/kg subcutaneous injection, once a day for 10 days starting day 29 (LMWH-d29). RESULTS: Comparing LMWH-d15 with LMWH-d29, plasma viscosity, whole blood viscosity, von Willebrand factor, serum fibrinogen, plasminogen activator inhibitor-1 and fibrin D-dimer were each significantly reduced; but thrombin plasminogen activator increased significantly whilst arterial PO2 and PCO2 improved significantly. CONCLUSION: The better time to use LMWH is the time when coagulation and fibrinolytic indices begin to change in COPD.

[Incidence of pulmonary embolism in patients with acute exacerbations of chronic obstructive pulmonary disease: a meta-analysis].

OBJECTIVE: To evaluate the incidence of pulmonary embolism in patients with acute exacerbations of chronic obstructive pulmonary disease (COPD). METHODS: Comprehensive searches as of June 2012 were performed in PubMed (1966-), Embase (1974-), Chinese Biomedical Literature Database (1978-), Chinese Journal Full-text Database (1979-) and VIP Database (1989-) for literatures on the incidence of pulmonary embolism in patients with acute exacerbations of COPD. Meta-analysis was conducted with Stata version 11.0. RESULTS: Among 2273 articles identified, 5 studies met the inclusion criteria (4 in English, 1 in Chinese). The total sample size was 762 patients, among whom 145 were diagnosed with pulmonary embolism. The incidence of pulmonary embolism ranged from 3.3% to 33.0%. Meta-analysis showed that the combined incidence was 15.8% (95%CI: 5.1%-26.4%). Among patients with acute exacerbations of COPD of unknown etiology, the incidence was 29.0% (95%CI: 20.8%-37.1%). CONCLUSIONS: There is a high incidence of pulmonary embolism in patients with acute exacerbations of COPD, especially among those of an unknown etiology. More attention should be paid to this population.