Objective: The aim of this paper is to identify the basic organizational structure and the key elements of integrated healthcare model of patients with Chronic Obstructive Pulmonary Disease (COPD) and propose an appropriate development strategy.Methods: Based on the literature review of research articles about integrated care on patients with COPD, an analysis was conducted with the help of the Chronic Care Model (CCM) which is a chronic disease management model.Results: From of a total 16 articles about 13 case studies were found.An integrated healthcare of COPD was carried out in 10 hospital-based or community-based care programs.Most of the patients were the elderly and health status were moderately severe or more severe.The components of healthcare programs varied from 4 to 12 included at least two CCM dimension.A coordinator or a case manager was appointed in all healthcare programs and a follow-up plan was made as well.Decision making was supported by clinic guideline and specialist resource in 9 integrated healthcare programs which community facilities involved.All programs included self-management with health education and individualized behavioral support was in 10 programs.The action plan was applied in 8 studies.8 studies using a clinical information system connected health care provider and patients.Conclusions: COPD integrated care program can be constructed according to the management model of chronic disease, and it is suggested that we can organize the COPD integrated care program based on CCM and the program comprises 4 organizational components of at least two CCM dimensions.The key elements of COPD integrated healthcare are to appoint a coordinator, to make a follow-up plan, and the necessity of community participation to support decision making, support self-management by education and individualized behavioral management with an action plan.

Objective:To investigate the effects of different doses of sodium arsenic (NaAsO 2) on mRNA transcription levels of nucleotide excision repair (NER) related genes in normal hepatocytes (L-02 cells) and the modification levels of histone H3 ninth lysine dimethylization (H3K9me2) in the promoter region. Methods:L-02 cells were treated with 0 (the control group) , 5, 10 and 20 μmol/L NaAsO 2 for 24 h ( n = 3). Single cell gel electrophoresis (SCGE) was used to detect DNA damage [Olive tail distance (OTM) and Tail DNA percentage (Tail DNA%)] in L-02 cells. The mRNA expression levels of Xeroderma pigmentosum (XP) gene A (XPA), XP gene D (XPD) and XP gene F (XPF) were detected by real-time fluorescence quantitative PCR. The modification levels of H3K9me2 in XPA, XPD and XPF gene promoter regions (CHIP1 and CHIP2) were detected by quantitative chromatin immunoprecipitation. Results:OTM and Tail DNA% were positively correlated with arsenic doses (in the control and 5, 10 and 20 μmol/L arsenic exposure groups, the values were 0.35 ± 0.09, 0.56 ± 0.18, 3.18 ± 0.31, 4.52 ± 0.55, 0.72 ± 0.05, 1.34 ± 0.26, 3.93 ± 0.43, 5.47 ± 0.65, respectively, r = 0.927, 0.948, P < 0.05). Compared with the control group, the mRNA expression levels of XPA, XPD and XPF in L-02 cells of 10 and 20 μmol/L arsenic exposure groups were significantly lower ( P < 0.05). Compared with the control group, the enrichment levels of H3K9me2 in XPA, XPD and XPF gene promoter regions (CHIP1 and CHIP2) in L-02 cells of 20 μmol/L arsenic exposure group were significantly higher ( P < 0.05). Conclusion:Arsenic may inhibit the transcription of NER related genes by increasing the enrichment level of H3K9me2 in the promoter regions (CHIP1 and CHIP2) of NER related genes, thereby reduce the DNA damage repair ability of L-02 cells, resulting in the aggravation of DNA damage.

Background and objective Lung cancer is a common malignancy and is the major determinant of overall cancer mortality worldwidely. Approximately 70％ of lung cancer patients will die from metastatic diseases. The aim of this study is to establish a Chinese lung adenocarcinoma cell line with high metastasis potency for exploring the mechanism of occurrence and development in lung cancer. Methods The cell came from the pericardial effusion of a fifty-year old male patient with lung adenocarcinoma and the cells in primary culture were obtained successfully. Immunodeficient mice tumorigenidty was assayed. The cell growth curve was mappinged Analysis of chromosome karyotype was tested. Tumor marker was detected by radioim-munoassay.The gene expression was measured by real-time quantitative PCR. Results The first passage cells were planted in im-munodeficiant mice subcutaneously and the tumorigenesis rate was 100％ as well as later passages. Under the microscope, the cell showed larger and semi-suspension, semi-adherence. Approximately 0.8x 106 cancerous ceils were injected into left cardiac ventri-cle or tail vein of immunodeficient mice resulted start to appear lower limb paralysis and spine swelling deformation in the mice after inoculation two-three weeks. The bone metastasis rate was 90％ in the tumor bearing mice by bone acintigraphy and pathol-ogy and only pulmonary metastasis 10％ at the same time. The chromosome karyotype analysis of the cells was sub-triploid. The tumor marker CEA was detected in higher secretion by radioimmunoassay in the cell culture suspension. Quantitative real-time PCK was used to examined and compared SPC-A-1 lung adenocarcinoma, VEGF-C, IL-6,IL,-8, genes were overexpressed. The novel cell line was named CPA-Yang1. Conclusion Tne novel strain CPA-Yang1 is an parental cell with characteristics of bone metastasis of Chinese lung adenocarcinoma. It has stable traits, highly metastatic ability and a good experimental modal for lungcancer research.

Background and objective Lung cancer is the leading cause of cancer-related death in men and wom-en. It is also the most common cause of brain metastases. A brain metastasis model is diffcult to be established because of the presence of the blood-brain barrier (BBB) and the lack of optimal methods for detecting brain metastasis in nude mice. hTus, the establishment of a Chinese lung adenocarcinoma cell line and its animal model with brain metastasis potency and in vivo research is of great signiifcance. Methods CPA-Yang1 cells were obtained from a patient with human lung adeno-carcinoma by lentiviral vector-mediated transfection of green lfuorescence protein. Intracardiac inoculation of the cells was performed in nude mice, and brain metastatic lesions were detected using micro 18F FDG-PET/CT scanners, small animal in vivo imaging system for lfuorescence, radionuclide and X ray fused imaging, magnetic resonance imaging (MRI) with sense body detection, and resection. hTe samples were divided into two parts for cell culture and histological diagnosis. hTe process was repeated in vivo and in vitro for four cycles to obtain a novel cell clone, CPA-Yang1-BR. Results A novel cell clone, CPA-Yang1-BR, was obtained with a brain metastatic rate of 50%. hTe use of MRI for the detection of brain metasta-ses has obvious advantages. Conclusion An experimental Chinese lung adenocarcinoma cell clone (CPA-Yang1-BR) and its animal model with brain metastasis potency in nude mice were established. MRI with sense body or micro MRI may be used as a sensitive, accurate, and noninvasive method to detect experimental brain metastases in intact live immunodeifcient mice. hTe results of this study may serve as a technical platform for brain metastases from lung adenocarcinoma.

Background and objective A great individual differences to chemotherapeutic effects existed in the patient with advanced lung cancer. How to choose the optimum regimens to achieve the individuation and maximum effect of chemotherapy for lung cancer is worth exploring. hTe study was designed to examine the effect of ex vitro chemo-sensitivity assay in xeno-free culture of autologous malignant effusion cells from patients with advanced lung adenocarcinoma.Methods hTe 50 treatment-naive patients with lung adenocarcinoma complicated with malignant pleural or pericardial effusions were enrolled. Effusions of all cases had been controlled by closed drainage and 300 mL-500 mL of which were retained under sterile condition from 25 cases (Chemo-sensitivity group). Primary malignant effusion cells were isolated from autologous effusions of the patients. hTen, xeno-free culture (average 11 days) were intervened with 8 chemotherapeutic drugs commonly used in clinical practice and were determined by CCK-8 assay. Optimum regimens were selected for chemotherapy based on the results of chemosensitivity test. As a contrast, chemotherapy regimens for the other 25 patients (Control group) were on the basis of physician’s clinical experience.Results Atfer four cycles of chemotherapy, in Chemo-sensitivity group, 17 (68.0%) cases were determined for partial response (PR), 5 (20.0%) cases for stable disease (SD), and the objective response rate (ORR) was 68.0%, the disease control rate (DCR) was 88.0%. Meanwhile, in Control group, 9 (36.0%) cases were determined for PR, 7 (28.0%) cases for SD, and, the ORR was 36.0%, the DCR was 64.0%. hTere were signiifcant differences between the two groups in ORR and DCR (P<0.05). To the end of follow-up, there were 21 cases of death in Chemo-sensitivity group as well as 22 cases in Control group. hTe mean progression-free survival (PFS) in Chemo-sensitivity group and Control group respec-tively were 10.0 months and 5.8 months, and the mean overall survival (OS) in the two groups were 30.2 months and 21.2 months respectively. hTere were also signiifcant differences between the two groups in PFS and OS (P<0.05). Furthermore, the adverse reactions in both groups were mild and controllable.Conclusion Xeno-free culture of autologous malignant effu-sion cells from patients with advanced lung adenocarcinoma andex vitro chemo-sensitivity assay are beneifcial to the rational choices of chemotherapeutic agents used in patients with lung adenocarcinoma complicated with malignant effusions, which is a worthy trial in personalized cell culture for individualized cancer therapy and further studies.

Objective:To establish the animal model of subchronic manganism, and to explore the effect of manganese on neurofunction of rats and the protective effect of curcumin on neurotoxicity of manganism rats.Methods:From July to December 2019, 80 SPF male SD rats were divided into 8 groups according to body weight by random number table method, which were blank control group, low, middle and high dose manganese exposure group, low, middle and high dose curcumin antagonistic group and curcumin group, with 10 rats in each group. The low, middle and high dose manganese groups were given intraperitoneal injection of 5 mg/kg, 10 mg/kg and 15 mg/kg MnCl 2·4H 2O respectively. The low, middle and high dose curcumin antagonistic groups were given 100 mg/kg, 200 mg/kg and 400 mg/kg curcumin orally along with 15 mg/kg MnCl 2·4H 2O intraperitoneal injection. Curcumin group was given 400 mg/kg curcumin orally. The rats were exposed to 5 days a week, once a day for 16 weeks. After exposure, neurobehavioral tests (balance beam test, Morris water maze, passive avoidance test) were carried out in each group. Hippocampus tissues were taken for pathological examination and oxidative stress indexes were detected. Results:The balance beam test results showed that, compared with the blank control group, the scores of balance beam of the rats in the middle and high dose manganese exposure groups increased ( P<0.05) . Compared with the high dose manganese exposure group, the balance beam scores of the low, middle and high dose curcumin antagonistic groups were decreased ( P<0.05) .The results of Morris water maze showed that, compared with the blank control group, the escape latency of middle and high dose manganese exposure groups was prolonged from the third day ( P<0.05) , and the average number of crossing the platform area of each manganese exposure group was decreased ( P<0.05) .Compared with the high dose manganese exposure group, the escape latency of the middle and high dose curcumin antagonistic groups was shortened ( P<0.05) , and the average number of crossing the original platform was increased ( P<0.05) . The results of passive avoidance test show that, compared with the blank control group, the number of errors were increased in middle and high dose manganese exposure groups ( P<0.05) . Compared with the high dose manganese exposure group, the number of errors in the passive avoidance test in the middle and high dose curcumin antagonistic groups were decreased ( P<0.05) . Pathological examination showed that the rats treated with manganses had different degrees of degeneration and necrosis of nerve cells, and the structure of nerve cells was blurred and the number of nerve cells decreased. The above phenomena were improved after curcumin antagonism. The results of oxidative stress index showed that, compared with blank control group, the activity of superoxide dismutase (SOD) decreased and the content of malondialdehyde (MDA) increased in the hippocampus of rats exposed to middle and high dose of manganese ( P<0.05) . Compared with the high dose manganese exposure group, the SOD activity increased and the MDA content decreased in the middle and high dose antagonist group ( P<0.05) . Conclusion:Subchronic manganese exposure can reduce the balance function, learning and memory ability of rats, and damage the hippocampal nerve cells in oxidative stress state. Curcumin can improve the balance function and learning and memory ability of rats with manganese poisoning, improve the hippocampal nerve damage caused by manganese exposure, and has a certain protective effect on manganese induced neurotoxicity.

Objective:To establish the animal model of subchronic manganism, and to explore the effect of manganese on neurofunction of rats and the protective effect of curcumin on neurotoxicity of manganism rats.Methods:From July to December 2019, 80 SPF male SD rats were divided into 8 groups according to body weight by random number table method, which were blank control group, low, middle and high dose manganese exposure group, low, middle and high dose curcumin antagonistic group and curcumin group, with 10 rats in each group. The low, middle and high dose manganese groups were given intraperitoneal injection of 5 mg/kg, 10 mg/kg and 15 mg/kg MnCl 2·4H 2O respectively. The low, middle and high dose curcumin antagonistic groups were given 100 mg/kg, 200 mg/kg and 400 mg/kg curcumin orally along with 15 mg/kg MnCl 2·4H 2O intraperitoneal injection. Curcumin group was given 400 mg/kg curcumin orally. The rats were exposed to 5 days a week, once a day for 16 weeks. After exposure, neurobehavioral tests (balance beam test, Morris water maze, passive avoidance test) were carried out in each group. Hippocampus tissues were taken for pathological examination and oxidative stress indexes were detected. Results:The balance beam test results showed that, compared with the blank control group, the scores of balance beam of the rats in the middle and high dose manganese exposure groups increased ( P<0.05) . Compared with the high dose manganese exposure group, the balance beam scores of the low, middle and high dose curcumin antagonistic groups were decreased ( P<0.05) .The results of Morris water maze showed that, compared with the blank control group, the escape latency of middle and high dose manganese exposure groups was prolonged from the third day ( P<0.05) , and the average number of crossing the platform area of each manganese exposure group was decreased ( P<0.05) .Compared with the high dose manganese exposure group, the escape latency of the middle and high dose curcumin antagonistic groups was shortened ( P<0.05) , and the average number of crossing the original platform was increased ( P<0.05) . The results of passive avoidance test show that, compared with the blank control group, the number of errors were increased in middle and high dose manganese exposure groups ( P<0.05) . Compared with the high dose manganese exposure group, the number of errors in the passive avoidance test in the middle and high dose curcumin antagonistic groups were decreased ( P<0.05) . Pathological examination showed that the rats treated with manganses had different degrees of degeneration and necrosis of nerve cells, and the structure of nerve cells was blurred and the number of nerve cells decreased. The above phenomena were improved after curcumin antagonism. The results of oxidative stress index showed that, compared with blank control group, the activity of superoxide dismutase (SOD) decreased and the content of malondialdehyde (MDA) increased in the hippocampus of rats exposed to middle and high dose of manganese ( P<0.05) . Compared with the high dose manganese exposure group, the SOD activity increased and the MDA content decreased in the middle and high dose antagonist group ( P<0.05) . Conclusion:Subchronic manganese exposure can reduce the balance function, learning and memory ability of rats, and damage the hippocampal nerve cells in oxidative stress state. Curcumin can improve the balance function and learning and memory ability of rats with manganese poisoning, improve the hippocampal nerve damage caused by manganese exposure, and has a certain protective effect on manganese induced neurotoxicity.