Kejing Ying

Value of quantitative analysis of circulating cell free DNA as a screening tool for lung cancer: a meta-analysis.

OBJECTIVE Quantitative analysis of circulating cell free DNA is considered as a possible aid for lung cancer screening. We aimed to comprehensively review the evidence for use of circulating cell free DNA to screen for lung cancer. METHODS After a systematic review of English language studies, sensitivity, specificity, and other measures of accuracy of circulating DNA assay in the diagnosis of lung cancer were pooled using random-effects models. Summary receiver operating characteristic curves were used to summarize overall test performance. RESULTS Ten studies met our inclusion criteria. The summary estimates for quantitative analysis of circulating cell free DNA in lung cancer screening in the studies included were as follows: sensitivity, 0.80 (95% confidence interval (CI), 0.77-0.83); specificity, 0.77 (95% CI, 0.74-0.80); positive likelihood ratio, 4.54 (95% CI, 2.66-7.76); negative likelihood ratio, 0.28 (95% CI, 0.19-0.40); and diagnostic odds ratio, 20.33 (95% CI, 10.12-40.86). CONCLUSIONS The current evidence suggests that the diagnostic accuracy of quantitative analysis of circulating DNA is not lower than conventional serum biomarkers for lung cancer screening, at least. However, it is not recommend for lung cancer screening alone, because its discrimination power is not very perfect. The value of circulating DNA assay in combination with conventional markers for lung cancer detection deserved further investigation.

Long noncoding RNA expression profiles of hypoxic pulmonary hypertension rat model.

OBJECTIVE Recently, long noncoding RNAs(lncRNAs) have been proved to be playing crucial roles in various biological processes, yet their role in hypoxic pulmonary hypertension (HPH) remains unclear. The aim of the present study is to investigate the lncRNA expression signatures in HPH rat model. METHODS Sprague Dawley rats were put in normobaric hypoxic chamber (FIO2 10%) eight hours a day or similar normoxic chamber for 3 weeks. Microarray was used to analyze the differential expression of lncRNAs and mRNAs between lung tissues of HPH rat model and control group. Dysregulated expression of selected lncRNAs was confirmed by Quantitative real-time PCR (qRT-PCR). RESULTS A total of 362 lncRNAs were identified to be significantly differentially expressed, among which 86 were up-regulated and 276 were down-regulated with fold-changes >/=2.0 between the two groups. The qRT-PCR results of lung tissues were in consistent with the microarray data. CONCLUSIONS The expression profile of lncRNAs was significantly altered in HPH rat model which may offer new insights into pathogenesis of this disease and could potentially provide novel diagnostic markers.

Nkx2-1: a novel tumor biomarker of lung cancer

Nkx2-1 (Nkx homeobox-1 gene), also known as TTF-1 (thyroid transcription factor-1), is a tissue-specific transcription factor of the thyroid, lung, and ventral forebrain. While it has been shown to play a critical role in lung development and lung cancer differentiation and morphogenesis, molecular mechanisms mediating Nkx2-1 cell- and tissue-specific expression in normal and cancerous lungs have yet to be fully elucidated. The recent identification of prognostic biomarkers in lung cancer, particularly in lung adenocarcinoma (ADC), and the different reactivity of patients to chemotherapeutic drugs have opened new avenues for evaluating patient survival and the development of novel effective therapeutic strategies. The function of Nkx2-1 as a proto-oncogene was recently characterized and the gene is implicated as a contributory factor in lung cancer development. In this review, we summarize the role of this transcription factor in the development, diagnosis, and prognosis of lung cancer in the hope of providing insights into the utility of Nkx2-1 as a novel biomarker of lung cancer.

Direct factor Xa inhibitors (rivaroxaban and apixaban) versus enoxaparin for the prevention of venous thromboembolism after total knee replacement: A meta-analysis of 6 randomized clinical trials

OBJECTIVE A meta-analysis of randomized controlled trials (RCTs) was performed to compare the efficacy and safety of direct factor Xa inhibitors (rivaroxaban and apixaban) with enoxaparin for the prevention of venous thromboembolism (VTE) after total knee replacement. METHODS A systematic literature search in Medline, EMBASE, EBSCO, Springer, Ovid and Cochrane library databases was performed to identify RCTs comparing rivaroxaban/apixaban with enoxaparin for the prevention of VTE after total knee replacement. The outcomes including deep vein thrombosis (DVT), pulmonary embolism (PE) and major bleeding were pooled using risk ratios (RRs) with their 95% confidence intervals (95% CIs) as statistic. RESULTS A total of 6 RCTs with 13,790 patients were included in this meta-analysis. Overall, the incidence of DVT was significantly decreased with the use of direct Xa inhibitors (both twice daily [b.i.d] and once daily [q.d.] regimes) comparing with the enoxaparin treatment (P<0.01); however, there was no significant influencing difference between direct Xa inhibitors (b.i.d. regime) and enoxaparin on the incidence of PE (P=0.06), while significantly lower rate was found for q.d. regime of direct Xa inhibitors (P=0.02). With respect to major bleeding, the pooled analysis did not demonstrate a significant difference between direct Xa inhibitors (b.i.d. and q.d. regimes) and enoxaparin (30mg and 40mg b.i.d.). CONCLUSION In conclusion, our results confirmed that direct Xa inhibitors (rivaroxaban and apixaban) were more effective for prevention of VTE after total knee replacement as compared with enoxaparin, without increasing major bleeding risk.

Malignant glomus tumor of the lung with multiorgan metastases: case report and literature review.

Glomus tumor is an exceedingly rare neoplasm that is derived from cells of the neuromyoarterial glomus or glomus body. It rarely occurs in the visceral organs where glomus body may be sparse or even absent, such as the stomach, intestines, mediastinum, and respiratory tract. It is unusual for a glomus tumor to demonstrate atypical or malignant histopathological characteristics. It is also rare for such a tumor to express clinically aggressive behavior. However, when metastasis does occur, this disease is often fatal. We herein report an interesting case of a middle-age woman admitted due to progressive cough and hemoptysis. A polypoid mass was found to occlude the left lingular lobar bronchus. Final histopathologic examination showed the presence of malignant glomus tumor, confirmed by immunoreactivity for smooth muscle actin and vimentin. Two months later, the patient developed abdominal distension and gastrointestinal bleeding. Further evaluation lead to the discovery of widespread metastatic disease to the gastrointestinal tract, spleen, and the left adrenal gland. We further entail a review of the literature on the clinicopathologic features and diagnosis of this uncommon tumor.

Transgelin overexpression in lung adenocarcinoma is associated with tumor progression

Hypoxia is a common feature of solid tumors and is associated with an increased likelihood of local recurrence and distant metastasis. Transgelin (TAGLN) is an actin cross-linking/polymerization protein that belongs to the family of actin-associated proteins, and there is evidence that TAGLN may be involved in the migration of epithelial cells by interacting with actin or promoting podosome formation. Cell migration is a key step of cancer metastatis. Thus, the aim of this study was to investigate the potential link between TAGLN protein levels and hypoxia in lung adenocarcinoma cells and to explore the possible functions and expression patterns of TAGLN in lung adenocarcinoma. We first examined the effects of altered TAGLN expression on cell migration under both normoxic and hypoxic conditions. Immunohistochemical (IHC) staining was also performed to examine TAGLN protein expression patterns in lung adenocarcinoma samples. Our results revealed that TAGLN was upregulated in the hypoxic lung adenocarcinoma cells. The inhibition of TAGLN expression in the cells using small interfering RNA (siRNA) led to a decreased migration ability. TAGLN was significantly overexpressed in the lung adenocarcinoma tissues compared to the adjacent tumor-free tissues. A high TAGLN expression correlated with an advanced TNM stage, lymph node metastasis and greater differentiation. TAGLN was upregulated in the human lung adenocarcinoma cell lines under hypoxic conditions, which contributed to the migration ability of the cells. Thus, our data suggest that TAGLN may be a viable therapeutic target and a potential biomarker for predicting the prognosis of patients with lung adenocarcinoma.

Diarrhea as initial manifestation of pulmonary artery intimal sarcoma: a case report and literature review.

Pulmonary artery intimal sarcoma (PAIS) is a rare malignant tumor that presents with nonspecific symptoms and may be misdiagnosed as thromboembolic disease. We report a case of a 40-year-old female who presented with diarrhea as the initial symptom, was misdiagnosed and received thrombolytic therapy for presumed pulmonary embolism. Progressive symptoms and subsequent surgery led to the diagnosis of PAIS, and early relapse after pulmonary endarterectomy. Her survival time was 17 months after pulmonary endarterectomy. To our knowledge, diarrhea as initial manifestation of PAIS has not been described.

Serum levels of IGFBP7 are elevated during acute exacerbation in COPD patients

Objective The purpose of this study was to explore the insulin-like growth factor binding protein 7 (IGFBP7) level in the serum of chronic obstructive pulmonary disease (COPD) patients during acute exacerbation (AE). Methods The study population consisted of 47 AECOPD patients, including 25 patients enrolled between January 2011 and February 2011 (the first group) and 22 patients enrolled from December 2011 to August 2012 (the second group) and 29 healthy controls. Chemiluminescence–linked immunoassay was used to detect serum IGFBP7 levels. For the second group patients, IGFBP7 and C-reactive protein (CRP) levels were measured both on the admission day and on the discharge day. Results Among the first group AECOPD patients, serum IGFBP7 levels were significantly elevated in AECOPD patients in the intensive care unit (ICU; 52.92±16.32 ng/mL), and in hospitalized AECOPD patients not in ICU (40.66±13.9), compared to healthy subjects (30.3±7.09 ng/mL; P<0.01). For the second group AECOPD patients, the increased IGFBP7 levels reduced after the patients had recovered (34.42±11.88 vs 27.24±7.2 ng/mL; P<0.01). During AE, the correlation coefficient between IGFBP7 and CRP was 0.357. In receiver operating characteristic analysis, the area under the curve was 0.799 for CRP, and 0.663 for IGFBP7 in distinguishing patients with AECOPD on the admission day from the discharge day. Conclusion Serum IGFBP7 levels were raised during AECOPD. Similar to the expression pattern of CRP, the IGFBP7 levels reduced after convalescence, suggesting that IGFBP7 might have a candidate role as a biomarker of AECOPD. No significant linear correlation was detected between IGFBP7 and CRP, indicating the probable different role for the two molecules in assessing AECOPD. Further study is needed to explore the value of IGFBP7 in differentiating phenotypes of AECOPD.

Recent Progress in Research on the Pathogenesis of Pulmonary Thromboembolism: An Old Story with New Perspectives

Pulmonary thromboembolism (PTE) is part of a larger clinicopathological entity, venous thromboembolism. It is also a complex, multifactorial disorder divided into four major disease processes including venous thrombosis, thrombus in transit, acute pulmonary embolism, and pulmonary circulation reconstruction. Even when treated, some patients develop chronic thromboembolic pulmonary hypertension. PTE is also a common fatal type of pulmonary vascular disease worldwide, but earlier studies primarily focused on the pathological changes in the blood component of the disease. With contemporary advances in molecular and cellular biology, people are becoming increasingly aware of coagulation pathways, the function of vascular smooth muscle cells, microparticles, and the inflammatory pathways that play key roles in PTE. Combined hypoxia and immune research has revealed that PTE should be regarded as a class of complex diseases caused by multiple factors involving the vascular microenvironment and vascular cell dysfunction.

Involvement of CapG in proliferation and apoptosis of pulmonary arterial smooth muscle cells and in hypoxia-induced pulmonary hypertension rat model

ABSTRACT Purpose: Actin-binding protein capping protein gelsolin-like (CapG) was preferentially expressed in human pulmonary arterial smooth muscle cells (PASMCs) under hypoxia, and reduced CapG expression was accompanied by impaired migration ability in vitro. We intended to investigate the effects of CapG on rat PASMCs and hypoxia-induced pulmonary hypertension (HPH) rat model. Materials and Methods: We investigated the effect of RNA interference-medicated down-regulation of CapG expression in rat PASMCs as well as in HPH rat model. The proliferation, apoptosis and cell cycle of PASMCs were evaluated. The HPH rat model was established by intratracheal instillation of lentiviral vector and subsequent hypoxia exposure for four weeks. Right ventricular systolic pressure, right ventricular hypertrophy and the percentage of medial wall thickness were measured to evaluate the development of HPH. Results: Knock-down CapG in PASMCs resulted in decreased proliferation, increased apoptosis and induced cell cycle inhibition. Down-regulation of CapG expression locally could attenuate pulmonary hypertension, pulmonary vascular remodeling and right ventricular hypertrophy in HPH rat model. Conclusions: Our study indicated that CapG participated in the pathogenesis of pulmonary vascular remodeling in HPH rats, which was probably mediated by promoting the proliferation and inhibiting the apoptosis of PASMCs. We proposed CapG modulating protective effects of pulmonary hypertension.