Nontuberculous mycobacteria pulmonary disease: A retrospective analysis / 中南大学学报(医学版)

To analyze the clinical characteristics and drug resistance in patients with non-tuberculous mycobacteria (NTM) pulmonary disease in Changsha Central Hospital of Hunan Province in recent three years.
 Methods: The clinical data of 153 patients with NTM pulmonary disease, who were diagnosed in Changsha Central Hospital of Hunan Province from February 2014 to May 2017, were retrospectively analyzed. According to the concentration of drug sensitivity test, the patients were divided into a low concentration group and a high concentration group. The status of drug sensitivity and drug resistance were examined.
 Results: Among 153 patients, 79 patients (51.63%) were male, 74 patients (48.37%) were female. The mean ages were (60.27±19.46) years. The NTM pulmonary disease mainly occurred in the individuals with bronchiectasis, and the course of disease was long (mean 7.8 years). The clinical symptoms were not specific and mostly misdiagnosed as pulmonary tuberculosis (92.81%). Mycobacterium avium-intracellulare (56.21%) and mycobacterium chelonae-abscess (20.92%) were the majority. The drug-resistance rate of the first-line and second-line anti-tuberculosis drugs was high. The majority was resistant to more than eight drugs, 38.56% patients in the low concentration group were resistant to total drugs, and 25.49% patients in the high concentration group were resistant to total drugs.
 Conclusion: The NTM pulmonary disease is easily misdiagnosed, and the drug resistance rate is high. Identification of mycobacterium species and detection of drug sensitivity play an important role in clinical diagnosis and treatment.

Autologous induced pluripotent stem cell transplantation for acute lung injury in rats / 中国组织工程研究

BACKGROUND: Embryonic stem cells and mesenchymal stem cells are two main cell sources for stem cell transplantation in the treatment of acute lung injury. There are few reports on the study of autologous induced pluripotent stem cells in the treatment of acute lung injury. OBJECTIVE: To investigate the possibility of induced pluripotent stem cells derived from autologous dermal fibroblasts injected through the caudal vein in the treatment of acute lung injury in rats. METHODS: Twenty-four Sprague-Dawley rats (provided by Beijing Vital River Laboratory Animal Technology Co., Ltd.) were randomly divided into three groups. The control group was intraperitoneally injected with normal saline, and the model group and the experimental group were intraperitoneally injected with lipopolysaccharide to make acute lung injury models in rats. At 24 hours after modeling, phosphate buffer solution was injected into the tail vein of the rats in the control and model groups, while the rats in the experimental group were given induced pluripotent stem cell suspension by the tail vein. The changes of lung tissue morphology, lung wet/dry weight ratio, pathological injury score, serum interleukin 1beta, interleukin 6 and tumor necrosis factor alpha levels were observed at 7 days after treatment. RESULTS AND CONCLUSION: (1) At 7 days after treatment, pulmonary interstitial edema, alveolar septum thickening, inflammatory cell infiltration, capillary congestion, irregular alveolar morphology, and exudate in the alveolar cavity were significantly improved in the experimental group. (2) At 7 days after treatment, the wet/dry weight ratio of lung tissue in the model and experimental groups was significantly higher than that in the control group, but the wet/dry weight ratio of lung tissue and pathological injury score in the experimental group were significantly lower than those in the model group (P < 0.01). (3) At 7 days after treatment, the levels of serum interleukin 1beta, interleukin 6 and tumor necrosis factor alpha were ranked as follows: model group> experimental group> control group, and there were significant differences between groups (P < 0.01). To conclude, the transplantation of induced pluripotent stem cells derived from autologous dermal fibroblasts can effectively alleviate acute lung injury and reduce serum inflammatory factor levels in rats.

Autologous induced pluripotent stem cell transplantation for acute lung injury in rats / 中国组织工程研究

BACKGROUND: Embryonic stem cells and mesenchymal stem cells are two main cell sources for stem cell transplantation in the treatment of acute lung injury. There are few reports on the study of autologous induced pluripotent stem cells in the treatment of acute lung injury. OBJECTIVE: To investigate the possibility of induced pluripotent stem cells derived from autologous dermal fibroblasts injected through the caudal vein in the treatment of acute lung injury in rats. METHODS: Twenty-four Sprague-Dawley rats (provided by Beijing Vital River Laboratory Animal Technology Co., Ltd.) were randomly divided into three groups. The control group was intraperitoneally injected with normal saline, and the model group and the experimental group were intraperitoneally injected with lipopolysaccharide to make acute lung injury models in rats. At 24 hours after modeling, phosphate buffer solution was injected into the tail vein of the rats in the control and model groups, while the rats in the experimental group were given induced pluripotent stem cell suspension by the tail vein. The changes of lung tissue morphology, lung wet/dry weight ratio, pathological injury score, serum interleukin 1beta, interleukin 6 and tumor necrosis factor alpha levels were observed at 7 days after treatment. RESULTS AND CONCLUSION: (1) At 7 days after treatment, pulmonary interstitial edema, alveolar septum thickening, inflammatory cell infiltration, capillary congestion, irregular alveolar morphology, and exudate in the alveolar cavity were significantly improved in the experimental group. (2) At 7 days after treatment, the wet/dry weight ratio of lung tissue in the model and experimental groups was significantly higher than that in the control group, but the wet/dry weight ratio of lung tissue and pathological injury score in the experimental group were significantly lower than those in the model group (P < 0.01). (3) At 7 days after treatment, the levels of serum interleukin 1beta, interleukin 6 and tumor necrosis factor alpha were ranked as follows: model group> experimental group> control group, and there were significant differences between groups (P < 0.01). To conclude, the transplantation of induced pluripotent stem cells derived from autologous dermal fibroblasts can effectively alleviate acute lung injury and reduce serum inflammatory factor levels in rats.

Influence of angiogenin-like protein 4 on pulmonary fibrosis / 中国医师杂志

Objective To investigate the important role of angiogenin-like protein 4 (Angptl4) in pulmonary fibrosis and to provide a new therapeutic targets for pulmonary fibrosis.Methods We established the pulmonary fibrosis animal models in rat by tracheal instillation of bleomycin.Then,we detected the expression of Angptl4 through real-time polymerase chain reaction (RT-PCR) and Western Blot.Rat lung fibroblast (RLF) was transfected into Angptl4-shRNA plasmid.Then we detected the changed collagen expression in RLF cells after transfection through RT-PCR and Western blot.Results The expression of Angptl4 was up-regulated in the bleomycin-induced rat pulmonary fibrosis model.The expression of both collagen Ⅰ and collagen Ⅳ in RLF cells transfected with Angptl4-shRNA plasmids were down-regulated compared with control after TGF-β treatment.Conclusions Inhibiting the expression of Angptl4 can reduce the expression of collagen fibers in lung tissue,then delaying the progression of pulmonary fibrosis.

Detection of expressing of miR-103/KLF4 in A549 lung cancer cells and A549/DDP resistant cells and validation of the targeted relationship / 中国医师杂志

Objective To study the expression and targeted relationship of miR-103/KLF4 (Krüppel like factor) in A549 and resistant cell lines of lung cancer.Methods To culture the A549 cell lines and A549/DDP (cisplatin) resistant cell lines in vitro and detect survival rates by methyl thiazolyl tetrazolium (MTT) method.Real-time polymerase chain reaction (RT-PCR) and Western blotting were used to test the expression of miR-103/KLF4 of these cell lines.Dual-luciferase reporter gene experiment to detect the targeted relationship.Results A higher expression of miR-103 and a obvious lower expression of KLF4 were observed in A549/DDP resistant cell lines.MiR-103 target KLF4-3'UTR (3'untranslated regions) directly in lung cancer cells.Conclusions In A549/DDP resistant cells,miR-103 can regulate KLF4 at target.

Clinical efficacy of vitamin support in lung adenocarcinoma patients treated with pemetrexed second-line chemotherapy / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To analyze the clinical efficacy and toxicity of vitamin support in lung adenocarcinoma patients treated with pemetrexed second-line chemotherapy.</p><p><b>METHODS</b>Two hundred and eighty-three patients with stage 3/4 lung adenocarcinoma treated at our hospital from August 2010 to August 2013 were included in this study. The lung adenocarcinomas in all the 283 patients were confirmed by pathology or cytology, all were EGFR-negative, and all patients received pemetrexed second line chemotherapy. The 283 patients were randomly divided into two groups: the improved treatment group (142 cases) and the conventional treatment group (141 cases). The patients of conventional treatment group received 400 µg folic acid per os daily for 7 days before the first dose of pemetrexed, and continued until 21 days after the last dose of pemetrexed. Besides, they received 1000 µg vitamin B12 injection at 7 days before the first dose of pemetrexed, and once per cycle of pemetrexed for 3 cycles after the last dose of pemetrexed. The patients of the improved treatment group took 400 µg folic acid daily per os from the day before the first dose to 21 days after the last dose of pemetrexed. They also received 500 µg vitamin B12 by injection one day before the first dose, and one day before each therapy cycle of pemetrexed therapy.</p><p><b>RESULTS</b>The mean number of cycles of pemetrexed chemotherapy was 4 in both groups. In the 142 patients of improved treatment group, complete response (CR) was observed in two cases, partial remission (PR) in 28, stable disease (SD) in 21, and progressive disease (PD) in 91 cases, with a total effective rate of 21.1%. While in the conventional treatment group, CR was observed in one case, PR in 27 cases, SD in 23 cases, and PD in 90 cases, with a total effective rate of 19.9%. The median progression-free survival (PFS) was 3.8 months in the improved treatment group and 4.2 months in the conventional treatment group (P=0.143). The toxicity of chemotherapy was mild in both groups, with no significant difference between the two groups (P>0.05). The most common side effects of hematological system were leukopenia and neutropenia, and the most common side effects of non-blood system were nausea and vomiting. The most common grade 3-4 toxic reaction in both groups was leukopenia and neutropenia, with no significant difference between the two groups (P>0.05). Multivariate analysis showed that the age of patients was an independent factor of grade 3-4 chemotherapy toxic reaction (P<0.05), while gender, the baseline level of PS score or blood system had no significant effect on the grade 3-4 chemotherapy toxic reaction (P>0.05).</p><p><b>CONCLUSIONS</b>Compared with the conventional treatment scheme, the improved treatment scheme has similar therapeutic effects and could be used more conveniently, while the toxic effects of chemotherapy are not increased at the same time. Our results indicate that pemetrexed-based chemotherapy does not need to delay the chemotherapy because of vitamin support treatment.</p>

Bronchoscopic argon plasma coagulation therapy for bronchial carcinoma / 中南大学学报(医学版)

Objective To evaluate the effect of bronchoscopic argon plasma coagulation thera-py on bronchial carcinoma. Methods Thirty-one bronchial carcinoma patients were diagnosed by bronchoscope and pathological tests, with or without atelectasis or obstructive pneumonia on chest X-ray or chest CT. Argon plasma coagulation therapy was performed through bronchoscope. The location of the airway lesions, the degree of obstruction, dyspnea index, and complications were evaluated. Results The patients with bronchial carcinoma were treated 1～4 times by bronchoscopic argon plas-ma coagulation therapy. Full effectiveness was achieved in 15 patients (48.4 %), partial in 12 (38.7%), and mild in the other 4 ( 12.9 % ). The overall effective rate was 100 %. Conclu-sion Bronchoscopic argon plasma coagulation therapy for bronchial carcinoma can remarkably reduce the tumor size, relieve clinical symptoms, and alleviate the obstruction caused by bronchial neoplasm. Brouchoscopic argon plasma coagulation therapy is an effective and safe method for patients with bron-chial carcinoma.

Study on apoptosis of human lung adenocarcinoma cell line A549/DDP induced by ginsenoside Rh₂ in vitro / 中国肺癌杂志

<p><b>BACKGROUND</b>Lung cancer is one of the leading causes of cancer-related death in mankind. To exploit antitumor drug from plant has been a highlight at home and abroad. The aim of this study is to investigate the apoptosis of human lung adenocarcinoma cell line A549/DDP induced by ginsenoside Rh₂ (G-Rh₂) and to explore its possible molecular mechanism.</p><p><b>METHODS</b>The growth inhibition effect of G-Rh₂ on A549/DDP cells was evaluated by MTT assay. Cell cycle analysis, apoptosis index and tumor related gene expression were detected by flow cytometry. The changes of sApo-1/Fas level in the cell culture supernatant were determined by ELISA method.</p><p><b>RESULTS</b>(1) G-Rh₂ significantly inhibited the growth of A549/DDP cells in a dose-time-de-pendent manner. (2) After 24 hours' treatment with G-Rh₂, apoptosis index of trial group was significantly higher than that of control group (P < 0.001). The proportion of cells in G0/G1 phase in trial group was much higher than that in control group (P < 0.01), while proportion in S phase in trial group was markedly lower than that in control group (P < 0.01). There was no significant difference in proportion in G2/M phase between trial group and control group (P > 0.05). (3) The positive expression rate of p53 and Fas in trial group was significantly higher than that in control group (P < 0.01, P < 0.001), while the positive expression rate of Bcl-2 in trial group was significantly lower than that in control group (P < 0.001). (4) The level of sApo-1/Fas in A549/DDP cell culture supernatant in trial group was remarkably lower than that in control group (P < 0.05).</p><p><b>CONCLUSIONS</b>G-Rh₂ can induce the apoptosis of A549/DDP cells. Its molecular mechanism may be up-regulating expression of p53 and Fas and down-regulating expression of Bcl-2.</p>

Effects of recombinant human tumor-necrosis factor related to apoptosis inducing ligand protein on apoptosis of human lung adenocarcinoma cell line resistant to cisplatin / 中国肺癌杂志

<p><b>BACKGROUND</b>Tumor-necrosis factor related to apoptosis inducing ligand protein(TRAIL), like tumor-necrosis factor (TNF) and Fas, is a member of TNF cytokine supper family. Many researches have showed that TNF-α can reverse the resistance to some chemotherapeutic agents in cancer cell lines, and some anticancer drugs can result in up-regulations of death receptor (DR) and further lead to the enhancement of apoptosis induced by TRAIL. In order to clarify if TRAIL can reverse the resistance to cisplatin in cancer cells, the effects of recombinant human tumor-necrosis factor related to apoptosis inducing ligand protein (rhTRAIL) on apoptosis in human lung adenocarcinoma cell lines resistant to cisplatin (DDP) in vitro was explored.</p><p><b>METHODS</b>Human lung adenocarcinoma cell lines resistant to cisplatin, A549/DDP cells, were cultured in regular condition. At 24 hours after TRAIL and DDP, alone or combined, microculture tetrazolium (MTT) dye was used to evaluate the cytotoxic effects. And besides, to detect the apoptotic effects of rhTRAIL on A549/DDP cells, flow cytometry assay was used to test the apoptosis proportion, diphenylamine assay (DPA) was applied to detect the percent of DNA fragmentation and Caspase-3 chluorometric assay was performed to test the activity of Caspase-3 among these cells.</p><p><b>RESULTS</b>A549/DDP cells were not sensitive to low-dose rhTRAIL alone. The rate of growth inhibition and the apoptotic indexes such as the apoptosis proportion, the percent of DNA fragmentation and the activity of Caspase-3, had all no significant changes with rhTRAIL concentration less than 25μg/L (P > 0.05). But treated with higher-dose rhTRAIL more than 50μg/L, the four values changed obviously: 68.6%, (27.13± 0.66)%, (37.4±2.0)% and 0.117±0.011, respectively (P < 0.05). With combination of different concentration of rhTRAIL and 3mg/L DDP, the cyto-toxic and apoptotic effect was comparatively more apparent. The combination of rhTRAIL and 3mg/L DDP presented synergistic effect on A549/DDP, 12.5μg/L concentration of rhTRAIL together with 3mg/L DDP could kill 30.4% of A549/DDP cells. Furthermore, the rate of cell apoptosis, percent of DNA fragmentation and activity of caspase-3 increased to (19.39±0.54)%,(17.3±4.1)% and 0.138±0.009, which were significantly different from those of rhTRAIL alone (P < 0.01).</p><p><b>CONCLUSIONS</b>High-dose rhTRAIL can also induce the cells resistant to cisplatin to apoptosis, but the cytotoxic and apoptotic effects of rhTRAIL alone are weaker than those of combination of rhTRAIL and low-dose cisplatin which can augment the apoptotic effect induced by rhTRAIL. rhTRAIL is expected to be an efficient biologic drug for treatment of lung cancer resistant to chemotherapy.</p>

Expression of COX-2 and its prognostic significance in non-small cell lung cancer / 中国肺癌杂志

<p><b>BACKGROUND</b>To investigate the expression of COX-2 and its relation to clinical pathophysiological features and prognosis in non-small cell lung cancer (NSCLC).</p><p><b>METHODS</b>The expression of COX-2 protein was detected in 52 NSCLC tissues by immunohistochemical (S-P) method.</p><p><b>RESULTS</b>The positive COX-2 expression was observed in 25 (48.1%) cases of NSCLC tissues. The positive rate of COX-2 expression was 76.5% and 34.3% in adenocarcinoma and squamous cell carcinoma respectively (P < 0.01). The positive rate of COX-2 expression in T3+T4 disease (92.3%) was remarkably higher than that in stage T1+T2 (33.3%) (P < 0.01). There was a remarkable difference in COX-2 expression rate between clinical stage I+II (28.1%) and clinical stage III+IV (80.0%) groups (P < 0.01). The positive rate of COX-2 expression was 83.3% in those with lymph node metastasis, but only 17.9% in those without lymph node metastasis (P < 0.01). In addition, there were significant differences in positive rate of COX-2 expression among patients with ≤2, > 2 but < 5, ≥5 years of survival span respectively (P < 0.01).</p><p><b>CONCLUSIONS</b>Overexpression of COX-2 in NSCLC, especially in adenocarcinoma, is closely related to invasion, lymph node metastasis and clinical stage of lung cancer. It may play a role in development of NSCLC, and also may be a prognostic marker.</p>

The expression and its clinical significance of MMP-2 and MMP-9 in non-small cell lung cancer / 中国肺癌杂志

<p><b>BACKGROUND</b>To investigate the expression and its clinical significance of MMP-2 and MMP-9 in non-small cell lung cancer (NSCLC), so as to provide reference in diagnosis, treatment and determining prognosis of NSCLC.</p><p><b>METHODS</b>MMP-2 and MMP-9 expression was detected in 32 lung cancer tissues, 32 paracancerous lung tissues and 10 benign pulmonary lesion tissues by immunohistochemical method with anti-MMP-2 and anti-MMP-9 antibody.</p><p><b>RESULTS</b>(1)Expression of MMP-2 (90%, 36/40) and MMP-9 (83%, 33/40) in cancer tissues was significantly higher than that in paracancerous tissues (22% and 13%) and benign pulmonary disease tissues (0) (P < 0.01). (2)Expression level of MMP-2 and MMP-9 was significantly related to lymph node metastasis and TNM staging, and histologic classification and differentiation (P < 0.05).</p><p><b>CONCLUSIONS</b>MMP-2 and MMP-9 expression in NSCLC tissue is remarkably higher than that in paracancerous tissues and benign pulmonary tissues. Detaction of MMP-2 and MMP-9 expression in lung cancer tissue might be helpful to determine metastasis, staging of the cancer, and predict the prognosis of patients with NSCLC.</p>

Research of nutritional support in COPD patients / 中国临床营养杂志

This stued examined the effects of nutritional support in 56 patients suffer from COPD. The influence of nutritional support on lung function and arteny blood gases after infusion of an amino acid solution (7% Fan Ming) were observed. The results suggested theft PaO2, FEV1. FVC levels were increased significantry compared to the control group. PaOz decreased significantly in Fan Ming infusion group compared 100 control group.