Yujie Lei

The clinical use of circulating microRNAs as non-invasive diagnostic biomarkers for lung cancers

Many studies have investigated the diagnostic role of circulating microRNAs (miRNAs) in patients with lung cancer; however, the results still remain inconclusive. An updated system review and meta-analysis was necessary to give a comprehensive evaluation of diagnostic role of circulating miRNAs in lung cancer. Eligible studies were searched in electronical databases. The sensitivity and specificity were used to plot the summary receiver operator characteristic (SROC) curve and calculate the area under the curve (AUC). The between-study heterogeneity was evaluated by Q test and I2 statistics. Subgroup analyses and meta-regression were further performed to explore the potential sources of heterogeneity. A total of 134 studies from 65 articles (6,919 patients with lung cancer and 7,064 controls) were included for analysis. Overall analysis showed that circulating miRNAs had a good diagnostic performance in lung cancers, with a sensitivity of 0.83, a specificity of 0.84, and an AUC of 0.90. Subgroup analysis suggested that combined miRNAs and Caucasian populations may yield relatively higher diagnostic performance. In addition, we found serum might serve as an ideal material to detecting miRNA as good diagnostic performance. We also found the diagnostic role of miRNAs in early stage lung cancer was still relatively high (the sensitivity, specificity and an AUC of stage I/II was 0.81, 0.82 and 0.88; and for stage I, it was 0.80, 0.81, and 0.88). We also identified a panel of miRNAs such as miR-21-5p, miR-223-3p, miR-155-5p and miR-126-3p might serve as potential biomarkers for lung cancer. As a result, circulating miRNAs, particularly the combination of multiple miRNAs, may serve as promising biomarkers for the diagnosis of lung cancer.

Tree shrew as a new animal model for the study of lung cancer

Animal models play a key role in identifying treatments for various types of cancer, including lung cancer. The aim of the present study was to develop a new animal model for lung cancer induction using tree shrews from the Yunnan region in China. Tree shrews are suitable for a full simulation of human disease because their structure, function and metabolism are adequately close to human. This animal may offer a new experimental animal model to be used in the study of lung cancer. In the present study, 80 healthy tree shrews were distributed in experimental and control groups. Animals in the experimental group received different concentrations of iodized oil suspension of 3-methylcholanthrene (3-MC) and diethylnitrosamine (DEN) while animals in the control groups received saline or lipiodol solvent via endotracheal instillation. In the 3rd, 5th, 7th, 9th and 11th weeks the body weights of the animals were measured and chest X-ray examinations were conducted. Pathological studies on the lung tissues were also performed and the pathological changes occurring in bronchial epithelium in all the groups were examined. Animals in the experimental group gradually lost their body weight. For tree shrews in the blank control and solvent control groups the survival rates were 100 and 80%, respectively while the survival rate for the experimental group was 0%. Results from the chest X-ray conducted on animals in the blank control and solvent control groups revealed no obvious abnormalities while in the experimental group high-density shadow spots within the perfusion sites were observed. Pathological studies performed on these high-density areas confirmed changes in the bronchial epithelium. In the experimental groups we also detected bronchial epithelial atypical hyperplasia, and apparent changes in carcinoma in situ. In conclusion, lung cancer was successfully induced in tree shrews by a one-time endotracheal introduction of iodized oil suspension of 3-MC and DEN.

Subcellular distribution and genotoxicity of silica nanoparticles in human bronchial epithelial cells

BACKGROUND Silicon nanoparticles are widely used in daily life. Therefore, they attract increased attention because of their potential biotoxicity to the lungs when inhaled. The aims of this study are to explore the organism distribution and genotoxicity of silica nanoparticles in human bronchial epithelial cells (BEAS-2B). METHODS The biodistribution of silica with different particle sizes in human bronchial epithelial cells was observed by transmission electron microscopy (TEM). DNA damage was detected by single-cell gel electrophoresis (comet assay). RESULTS TEM revealed that SiO₂ nanoparticles with different sizes can be uptaken by cells and be localized in the cytoplasm and the nucleus. Compared with micro-silica, nano-silica in BEAS-2B cells can inflict more severe DNA damage (P<0.05). CONCLUSIONS The particle size of silica nanoparticles can be used to determine their distribution in biological cells. Compared with micro-silica, nano-silica has higher genotoxicity.

Research on fast track surgery application in lung cancer surgery

背景与目的 快速康复外科(fast track surgery, FTS)通过减少手术病人生理和心理的创伤应激, 从而达到病人快速康复的目的。本研究旨在探讨FTS技术在肺癌手术中应用的可行性。 方法 选取80例适合单叶肺叶切除手术治疗的肺癌患者, 随机分为实验组及对照组, 实验组接受FTS方案治疗、对照组接受传统方法治疗。比较两组术后不同时间的疼痛程度、肺不张发生率、胸腔积液发生率、术后住院时间及住院总费用。 结果 FTS方案组:术后1 h、6 h、12 h、24 h、48 h疼痛VAS评分均明显低于传统治疗组; 肺不张发生率为10.53%, 胸腔积液发生率为26.31%, 术后住院时间(4±1)d, 住院总费用(1.56 ±0.76)万元。对照组:肺不张发生率为33.33%, 胸腔积液发生率为22.22%, 术后住院时间(9±1)d, 总费用(2.36 ±0.54)万元。两组比较:术后疼痛程度(视觉模拟评分)明显低于对照组, 差异有统计学意义(P < 0.01);肺不张发生率(P=0.035), 住院时间(P=0.021)及住院总费用(P=0.024)的组间差异均有统计学意义; 胸腔积液发生率的组间差异无统计学意义(P=0.223)。 结论 FTS方案的应用可有效促进肺癌患者术后的康复, 减少术后并发症发生, 缩短住院时间, 降低住院费用。BACKGROUND AND OBJECTIVE Fast track surgery (FTS) is a systematical method to accelerate the recovery of surgical patients by reducing the physical and mental trauma stress of them. The research is to investigate the feasibility of FTS application in lung cancer surgery. METHODS A total of 80 cases of lung cancer patients with single leaf lobotomy resection were randomized into two groups. While the experimental group was treated with the conception of FTS, and the control group was treated with the traditional methods. The incident rate of post-operation pain degrees, telecasts, pleural effusion, the post-operation time stay in hospital time and the total cost during hospitalization in two groups were compared respectively. RESULTS In FTS group: the VAS score of post-operation pain at 1 h, 6 h, 12 h, 24 h and 48 h all significantly decreased compared to the traditional therapy group. The incidence rate of telecast was 10.53%. The incidence rate of pleural effusion was 26.31%. The length of stay after operation was (4 +/- 1) d and the total cost was RMB 15 600 +/- 7 600. In the control group, the above values were 77.78%, 33.33%, 22.22%, (9 +/- 1) d, RMB 23 600 +/- 5 400, respectively. The post operation pain (VAS method) of FTS group was remarkablely below the control group. There has significant difference of the incident rate of telecasts, stay time in hospital and the total cast in two groups (P < 0.05). No significant difference was observed in the incident rate ofpleural effusion. CONCLUSION The new methods of FTS can apparently accelerates recovery after lung cancer resection, reduces complications, shorten timestay in hospital and cut down the total cost.

Expression of PANDA, LincRNA-p21, PUMA in lung tissues of lung cancer patients in the Xuanwei and non-Xuanwei areas of Yunnan Province

Aim: To study the expression of PANDA, LincRNA-p21, and PUMA in lung tissue of patients with lung cancer from Xuanwei of Yunnan Province. Methods: Forty-five cases of lung cancer patients from Xuanwei and 42 lung cancer cases from non-Xuanwei were enrolled. Extraction of RNA was done using the Trizol kit. Real-time fluorescence quantitative PCR assay was done to obtain the relative expression. Results: Expressions of PANDA, LincRNA-p21, and PUMA in male and female patients or in squamous cell carcinoma and adenocarcinoma were not significantly different (P > 0.05). However, expression of LincRNA-p21 in Xuanwei patients was higher than non-Xuanwei patients (P < 0.05). Expression of PUMA in tumor tissue was lower than that in normal lung tissue (P < 0.05), and in Xuanwei patients was lower than non-Xuanwei patients (P < 0.05). In patients from non-Xuanwei regions, expression of LincRNA-p21 in patients with smoking index > 400 was higher than in those < 400 and non-smokers. Conclusion: Expressions of PANDA, LincRNA-p21, and PUMA in lung tissues have no gender differences or tissue specificity. High expression of LincRNA-p21 in Xuanwei patients may have relationship with cell damage caused by coal burning pollution in Xuanwei.

Association of Inorganics Accumulation with the Activation of NF-κB Signaling Pathway and the iNOS Expression of Lung Tissue in Xuanwei Lung Cancer Patients

BACKGROUND AND OBJECTIVE Indoor air pollution induces asthma, leads to chronic obstructive pulmonary disease, and may promote lung cancer. Our previous studies found that the accumulation of inorganic particulate matter that is due to indoor air pollution can lead to damage to alveolar cells and activation of signaling pathway, and ultimately provoke tumorigenesis. The aim of this study is to explore the accumulation of inorganics and activation of nuclear factor κB (NF-κB)-inducible nitric oxide synthase (iNOS) signaling pathway of lung tissue in Xuanwei lung cancer patients. METHODS From December 2013 to November 2014, 48 cases Xuanwei patients with lung cancer who underwent surgical treatment from the Third Affiliated Hospital of Kunming Medical University were enrolled in this study and compared with lung cancer patients from other regions. The ultrastructure of postoperative specimens was observed by transmission electron microscopy (TEM) to explore the occurrence of inorganic particles. Serum cytokines were analyzed. Then, the expression levels of NF-κB-p65 protein and iNOS protein in postoperative specimens was explored by immunohistochemistry and Western blot. Finally, 8-OHdG accumulation in lung cancer tissues and urine was measured. RESULTS A large number of nanoscale inorganics were observed in alveolar type II cells and macrophages located in adjacent tissues of lung cancer with Xuanwei patients. Silicon (Si) content was found in inorganic elemental analysis. The serum interleukin (IL)-1β levels (31.50 ± 19.16) pg/mL of Xuanwei lung-cancer patients were remarkably higher than those from other regions (11.33 ± 6.94) pg/mL (P<0.01), with statistically significant difference. The pathological tissues of Xuanwei lung-cancer patients express NF-κB-p65, and iNOS expression were significantly higher than those of patients from non-Xuanwei regions. No significant difference was found between cancerous and normal adjacent tissues. Xuanwei lung-cancer tissues and urine 8-OHdG level (40.124 ± 8.597) ng/mgCr were significantly higher than those of patients from other regions (25.673 ± 7.986) ng/mg Cr (P<0.05), with statistically significant difference. CONCLUSIONS The accumulation of inorganics and the activation of NF-κB-iNOS signaling pathway may contribute to Xuanwei lung cancer.
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Study of the Changes on Tree Shrew Bronchial Epithelium Induced by Xuanwei Bituminous Coal Dust

BACKGROUND AND OBJECTIVE Lung cancer is the type of cancer with the highest incidence and mortality in numerous countries and regions. Establishing an appropriate animal model that can be used to simulate lung cancer etiology, pathogenesis, and similar processes, is urgent. We explore the feasibility of establishing a lung cancer model induced by Xuanwei bituminous coal dust PM10 (particulate matter with diameters of 10 μm or less), which affects bronchial epithelium of tree shrews. METHODS The neck skin of adult tree shrews is dissected, and the thyroid cartilage is fully exposed. Subsequently, the weak part at the top of the thyroid cartilage is treated with intratracheal agents by perfusion via a special infusion needle puncture method. Regular X-ray examination and lung tissue biopsy were performed on the sacrificed animals to observe changes in pulmonary imaging and bronchial epithelial cells after perfusion of Xuanwei bituminous coal dust PM 10. RESULTS The tree shrews of the experimental group (exposed to bituminous coal dust) died in a week after perfusion with PM10, whereas no animal died until the end of the experiment in the blank control and the solvent control groups. Sections of lung tissue biopsy of the regularly killed tree shrews were stained with hematoxylin and eosin. The lung tissues of tree shrews in the experimental group showed a serial changes caused by bronchial epithelial hyperplasia, such as squamous metaplasia, dysplasia, and early invasive carcinoma, whereas no significant pathological changes were observed in the blank control and solvent control groups. CONCLUSIONS Endotracheal infusion of Xuanwei bituminous coal dust PM10 induces lung cancer in tree shrews. Thus, the lung cancer model was established.
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Effects of selenium and reduced glutathione on the proliferation and apoptosis of XWLC-05 cell

BACKGROUND Selenium is an essential micronutrient for mammals but toxic in large amounts. Most studies indicate that selenium has inhibitory effect on cancer. The aim of this study is to investigate the effects of selenium and reduced glutathione (GSH) combined application on the proliferation and apoptosis of human lung adenocarcinoma cell line XWLC-05. METHODS XWLC-05 cells were respectively treated in vitro by four factors (sodium selenite, GSH, sodium selenite+GSH and blank control (RMPI-1640 +10% calf serum) in different concentrations for 24 h. Cell growth inhibition rates were determined by MTT assay, cytomorphology was observed under inverted phase contrast microscope and changes of cell cycle were detected by Flow Cytometry (FCM). RESULTS Both selenium and GSH individual on the XWLC-05 cells were found to possess obvious growth inhibition effect on the XWLC-05 cells. Selenium and GSH combined application on the XWLC-05 cells had cooperative inhibition effect (P <0.01). The inhibition rate was increased in a dose-dependent relationship as selenium with concentrations between (0.5-4.0) mug/mL (P <0.01) whether it was selenium single factors or selenium and GSH combined effect. FCM results showed that some XWLC-05 cells were induced apoptosis and G1 phase cells were markedly increased and S, G2/M phase cells decreased in both selenium individual groups and selenium and GSH combined groups. CONCLUSIONS Selenium and GSH combined application on XWLC-05 cells can enhance directly the cell growth inhibitory effect compared with selenium and GSH individual. The mechanism seems to inhibit the synthesis of RNA and protein and prevent cells from entering S phase.