Competing risk nomogram and risk classification system for evaluating overall and cancer-specific survival in neuroendocrine carcinoma of the cervix: a population-based retrospective study.

OBJECTIVE: Neuroendocrine carcinoma of the cervix (NECC) is a rare malignancy with poor clinical prognosis due to limited therapeutic options. This study aimed to establish a risk-stratification score and nomogram models to predict prognosis in NECC patients. METHODS: Data on individuals diagnosed with NECC between 2000 and 2019 were retrieved from the Surveillance Epidemiology and End Results (SEER) database and then randomly classified into training and validation cohorts (7:3). Univariate and multivariate Cox regression analyses evaluated independent indicators of prognosis. Least absolute shrinkage and selection operator (LASSO) regression analysis further assisted in confirming candidate variables. Based on these factors, cancer-specific survival (CSS) and overall survival (OS) nomograms that predict survival over 1, 3, and 5 years were constructed. The receiver operating characteristic (ROC) curve, the concordance index (C-index), and the calibration curve estimated the precision and discriminability of the competing risk nomogram for both cohorts. Finally, we assessed the clinical value of the nomograms using decision curve analysis (DCA). RESULTS: Data from 2348 patients were obtained from the SEER database. Age, tumor stage, T stage, N stage, chemotherapy, radiotherapy, and surgery predicted OS. Additionally, histological type was another standalone indicator of CSS prognosis. For predicting CSS, the C-index was 0.751 (95% CI 0.731 ~ 0.770) and 0.740 (95% CI 0.710 ~ 0.770) for the training and validation cohorts, respectively. Furthermore, the C-index in OS prediction was 0.757 (95% CI 0.738 ~ 0.776) and 0.747 (95% CI 0.718 ~ 0.776) for both cohorts. The proposed model had an excellent discriminative ability. Good accuracy and discriminability were also demonstrated using the AUC and calibration curves. Additionally, DCA demonstrated the high clinical potential of the nomograms for CSS and OS prediction. We constructed a corresponding risk classification system using nomogram scores. For the whole cohort, the median CSS times for the low-, moderate-, and high-risk groups were 59.3, 19.5, and 7.4 months, respectively. CONCLUSION: New competing risk nomograms and a risk classification system were successfully developed to predict the 1-, 3-, and 5-year CSS and OS of NECC patients. The models are internally accurate and reliable and may guide clinicians toward better clinical decisions and the development of personalized treatment plans.

UPDATED UNDERSTANDING OF THE MOLECULAR TARGETS OF RADIOIODINE IN DIFFERENTIATED THYROID CANCER.

Radioactive iodine (RAI) therapy is a mainstay adjuvant treatment for thyroid cancer. Administration of RAI therapy after total or near-total thyroidectomy has shown a survival advantage in numerous properly selected patients. However, the role of RAI therapy after reoperation for persistent or recurrent differentiated thyroid carcinomas (DTCs) is unclear. One reason may be the possible downregulation of the I- transport system after primary surgery. RAI is transported by the sodium iodide symporter (NIS), PENDRIN, anoctamin 1 (ANO1) and cystic fibrosis transmembrane conductance regulator (CFTR) and emits ß particles that destroy follicular cells. The identification of pathways of iodide (I-) transport has allowed use of the transport system to render tumours susceptible to RAI treatment via gene therapy. This review focuses on the effect of RAI therapy in follicular cell-derived thyroid cancers and offers potential novel targets that enable improved radioiodine uptake and thus an improved prognosis of thyroid cancer.

[Efficacy and safety of autologous hematopoietic stem cell transplantation in elderly multiple myeloma patients: a single center retrospective study].

Objective: To evaluate the efficacy and safety of autologous hematopoietic stem cell transplantation (auto-HSCT) in elderly patients (≥65 years old) with multiple myeloma (MM) . Methods: From June 1, 2006 to July 31, 2020, 22 MM patients (≥65 years old) who were diagnosed in the First Affiliated Hospital, Sun Yat-sen University and received novel drug induction followed by auto-HSCT were analyzed retrospectively. These patients were evaluated for important organ functions before transplantation, and the International Myeloma Working Group frail score was used in 2016 to screen out transplant-eligible patients. Results: The median (interquartile range, IQR) age at the time of transplantation of the 22 patients was 66.75 (IQR 4.50) years. A total of 20 patients received stem cell mobilization. The median number of mononuclear cells collected was 4.53×10(8)/kg, that of CD34(+) cells was 3.37×10(6)/kg, and the median number of apheresis procedures performed was 2. After stem cell transfusion, the median time of neutrophil implantation was 11 days, that of platelet implantation was 13 days, and the treatment-related mortality was 0 at 100 days after transplantation. The median follow-up was 48.7 months. The median time to progression time was not reached, and the median overall survival time was 111.8 months. Conclusion: Auto-HSCT is a safe and effective treatment for selected elderly patients of 65 years or older with MM.

[New agents-based induction chemotherapy followed by autologous stem cell transplantation and maintenance treatment strategy for multiple myeloma: a single center retrospective study of 300 cases].

Objective: To examine the survival and influential factors of an integrated approach of novel agents, autologous hematopoietic stem cell (auto-HSCT) , and maintenance therapy in patients with multiple myeloma (MM) patients from a single center over the past 15 years. Methods: In our center, 300 MM patients who received an integrated strategy of new agents, auto-HSCT, and maintenance therapy over 15 years were retrospectively and prospectively analyzed. Results: The complete remission rates (CR) and ≥very good partial remission rates (VGPR) following induction therapy, transplantation, and maintenance therapy were respectively 35.3% and 55.2% , 72.4% and 80.0% , 89.2% , and 93.4% . When compared to patients receiving double-drug induction, the ≥VGPR and ORR of patients receiving triple-drug induction were improved. No difference existed in CR, ≥VGPR, and ORR between the PAD (bortezomib + liposome doxorubicin+ dexamethasone) and RAD (lenalidomide + liposome doxorubicin + dexamethasone) regimens, but the benefits speed differed. The negative rate of flow minimal residual disease following induction, transplantation, and maintenance was 18.8% (54 cases) , 41.4% (109 cases) , and 58.7% (142 cases) , respectively. The median time to progress (TTP) was 78.7 months and the median overall survival (OS) was 109 months. The median TTP for RISS-Ⅰ-Ⅲ patients were 111.8 months, 77.4 months, and 30.6 months, and the median OS was 118.8 months, 91.4 months, and 48.5 months, respectively. At various points during treatment, the TTP and OS of patients obtaining CR and MRD negative were longer than those of patients who did not obtain CR and MRD negative. TTP was noticeably shorter in high-risk cytogenetic patients compared to standard-risk patients even when CR was acquired during induction. There was no difference in TTP between patients with high-risk cytogenetics and those with standard-risk cytogenetics if MRD negative was acquired during induction. According to a multivariate analysis, the R-ISS stage was a poor predictor of TTP and OS at various treatment intervals. Therapeutic effectiveness was a newly independent prognostic factor following treatment. Conclusion: A median survival of almost 10 years is possible for MM patients who receive an integrated strategy of induction regimens followed by auto-HSCT and maintenance therapy, which significantly improves prognosis. However, this approach did not significantly benefit high-risk cytogenetic MM patients.

Cell-free DNA from bile outperformed plasma as a potential alternative to tissue biopsy in biliary tract cancer.

BACKGROUND: Biliary tract cancers (BTCs) are rare and highly heterogenous malignant neoplasms. Because obtaining BTC tissues is challenging, the purpose of this study was to explore the potential roles of bile as a liquid biopsy medium in patients with BTC. PATIENTS AND METHODS: Sixty-nine consecutive patients with suspected BTC were prospectively enrolled in this study. Capture-based targeted sequencing was performed on tumor tissues, whole blood cells, plasma, and bile samples using a large panel consisting of 520 cancer-related genes. RESULTS: Of the 28 patients enrolled in this cohort, tumor tissues were available in eight patients, and plasma and bile were available in 28 patients. Somatic mutations were detected in 100% (8/8), 71.4% (20/28), and 53.6% (15/28) of samples comprising tumor tissue DNA, bile cell-free DNA (cfDNA), and plasma cfDNA, respectively. Bile cfDNA showed a significantly higher maximum allele frequency than plasma cfDNA (P = 0.0032). There were 56.2% of somatic single-nucleotide variant (SNVs)/insertions and deletions (indels) shared between bile and plasma cfDNA. When considering the genetic profiles of tumor tissues as the gold standard, the by-variant sensitivity and positive predictive value for SNVs/indels in bile cfDNA positive for somatic mutations were both 95.5%. The overall concordance for SNVs/indels in bile was significantly higher than that in plasma (99.1% versus 78.3%, P < 0.0001). Moreover, the sensitivity of CA 19-9 combined with bile cfDNA achieved 96.4% in BTC diagnosis. CONCLUSION: We demonstrated that bile cfDNA was superior to plasma cfDNA in the detection of tumor-related genomic alterations. Bile cfDNA as a minimally invasive liquid biopsy medium might be a supplemental approach to confirm BTC diagnosis.

[Balectin-3 affects the stability of vulnerable coronary atherosclerosis plaques by targeted modulation of lncARSR].

OBJECTIVE: To investigate the mechanism by which galectin-3 (Gal-3) affects the stability of vulnerable coronary atherosclerosis plaques through long non-coding RNA ARSR (lncARSR). METHOD: Male BALB/c mice were randomly divided into normal diet group, high-fat diet group, high-fat diet+lncARSR inhibitor group (n=20). The high-fat diet contained 15% fat and 0.25% cholesterol, and lncARSR inhibitor was injected intravenously at 50 nmol/L every other day. After 12 weeks of high-fat diet feeding and treatment, the mice were euthanized for analyzing coronary atherosclerosis and plaque damage using Sudan IV and oil red O staining. The protein expressions of Gal-3 and ARSR in the coronary artery of the mice were analyzed with Western blotting, and the expressions of PI3K and Akt were detected with immunohistochemistry. The coronary artery tissues were harvested from normal mice for cell culture, and the isolated cells were transfected with a Gal-3 mimic or a Gal-3 inhibitor. At 24 h after the transfection, dual luciferase reporter gene assay was performed to determine the target relationship between Gal-3 and lncARSR; the mRNA expressions of tumor necrosis factor (TNF-α), interleukin-ß (IL-ß) and IL-6 in the transfected cells were detected with RT-qPCR. RESULTS: The positively stained areas by Sudan IV and red oil O and the protein expression of lncARSR were the lowest in normal diet group and the highest in high-fat diet group (P < 0.05). The protein expression of PI3K and Akt and the mRNA expression of TNF-α, IL-ß and IL-6 in high-fat diet group were higher than those in normal diet group. The protein expression of PI3K and Akt and the mRNA expression of TNF-α, IL-ß and IL-6 in high-fat diet+ lncARSR inhibitor group were significantly lower than those in high-fat diet group (P < 0.05). In the cell experiment, the activity of WT-lncARSR was significantly higher in Gal-3 mimic transfection group than in the control group and Gal-3 inhibition group (P=0.026), and was the lower in Gal-3 inhibition group than in the control group (P=0.017). CONCLUSION: Gal-3 and lncARSR are overexpressed in coronary atherosclerosis. Through a mechanism for targeted inhibition of lncARSR, Gal-3 regulates the PI3K/ Akt signaling pathway to suppress inflammation and thus regulate the stability of vulnerable coronary atherosclerosis plaques.

Platelet PD-L1 suppresses anti-cancer immune cell activity in PD-L1 negative tumors.

Strategies that interfere with the binding of the receptor programmed cell death protein-1 (PD-1) to programmed death ligand-1 (PD-L1) have shown marked efficacy against many advanced cancers, including those that are negative for PD-L1. Precisely why patients with PD-L1 negative tumors respond to PD-1/PD-L1 checkpoint inhibition remains unclear. Here, we show that platelet-derived PD-L1 regulates the growth of PD-L1 negative tumors and that interference with platelet binding to PD-L1 negative cancer cells promotes T cell-induced cancer cytotoxicity. These results suggest that the successful outcomes of PD-L1 based therapies in patients with PD-L1 negative tumors may be explained, in part, by the presence of intra-tumoral platelets. Altogether, our findings demonstrate the impact of non-cancer/non-immune cell sources of PD-L1 in the tumor microenvironment in the promotion of cancer cell immune evasion. Our study also provides a compelling rationale for future testing of PD-L1 checkpoint inhibitor therapies in combination with antiplatelet agents, in patients with PD-L1 negative tumors.

[Thyroid disruptor p, p'-DDE inhibited the expression of LHX4 and DIS3L protein in Nthy-ori-3-1 cells].

Objective: To observe the changes of LHX4 and DIS3L mRNA and protein expression in Nthy-ori-3-1 cells after the treatment of thyroid disruptor p, p'-DDE. Methods: Nthy-ori-3-1 cells in logarithmic growth phase were treated with 0, 0.5, 1.0, 2.0 and 5.0 µg/ml p, p'-DDE solution. The growth state and morphology of the cells were observed by microscope. The mRNA levels of LHX4 and DIS3L were detected by real-time fluorescent quantitative PCR, and the protein expression levels of LHX4 and DIS3L were detected by Western blot. Results: when the concentrations of p, p'-DDE were 0, 0.5, 1.0 and 2.0 µg/ml, Nthy-ori-3-1 cells grew normally. There were 33 differential genes in 2.0 µg/ml group, among which 13 genes were down regulated and 20 genes were up-regulated. Compared with the control group, the protein expression levels of LHX4 and DIS3L in 1.0 and 2.0 µg/ml groups were significantly decreased (P<0.05) , and the relative expression levels of LHX4 and DIS3L protein mRNA in 1.0 µg/ml group were significantly decreased (P<0.05) . Conclusion: p, p'-DDE can affect the protein expression of LHX4 and dis3l in nthy-ori-3-1 cells.

[High dose melphalan (HDM) is superior to cyclophosphamide plus etoposide and busulfan (CVB) as the conditioning regimen in autologous stem cell transplantation for multiple myeloma].

Objective: To compare the efficacy, response and survival between high-dose melphalan (HDM) and cyclophosphamide+ etoposide+ busulfan (CVB) as the conditioning regimen in autologous stem cell transplantation (ASCT) for newly diagnosed multiple myeloma (NDMM) . Methods: Retrospectively enrolled 123 consecutive NDMM patients who had received PAD induction with subsequent ASCT from Jan 2011 to Aug 2017. The CVB group and HDM group had 82 and 41 patients respectively. Results: ①No differences existed between these 2 groups in non-hematological side effects. ②Patients of CVB group had faster neutrophil and platelet engraftment time, with the median neutrophil engraftment time of 10 (9-35) day vs 11 (9-12) day for patients of HDM group (z=-3.433, P=0.001) , and with median platelet engraftment time of 11 (7-55) day vs 13 (10-35) day for patients of HDM group (z=-3.506, P<0.001) . CVB group entered neutropenia and severe thrombocytopenia more earlier than the HDM group, resulting similar neutropenia duration and severe thrombocytopenia duration between the CVB group and HDM group. However, patients of CVB group had significantly longer fever persistent time and antibiotic administration time. ③The response rate was significantly lower in patients of CVB group vs. patients of HDM group (9/46 vs 14/28, P=0.021) . Further, the minimal residual disease (MRD) negative rate at 3(rd) month post-transplantation seemed to be lower in CVB group than that in HDM group (31.7%vs 48.8%, P=0.065) . ④Both the univariate and multivariate analysis showed that HDM and CVB groups had similar duration to progression (TTP) (P=0.619) and overall survival (OS) (P=0.295) . Conclusion: HDM conditioning regimen is superior to CVB regimen in hematological side effects, tumor burden reduction and administration convenience. However, these two regimen had similar TTP and OS in MM patients receiving ASCT.

[Bortezomib-based induction chemotherapy followed by autologous hematopoietic stem cell transplantation and maintenance in 200 patients with multiple myeloma: long-term follow-up results from single center].

Objective: To study the efficacy, safety and long-term outcomes of integrated strategy of bortezomib-based induction regimens followed by autologous hematopoietic stem cell (ASCT) and maintenance therapy in Chinese multiple myeloma (MM) patients. Methods: 200 MM patients receiving integrated strategy of bortezomib--based induction regimens followed by ASCT and maintenance therapy were retrospectively and prospectively analyzed from December 1. 2006 to April 30. 2018. Results: The complete remission rates (CR) and better than very good partial remission rates (VGPR) after induction therapy, transplantation and maintenance therapy were respectively 31% and 75.5%, 51.8% and 87.7%,73.6% and 93.4%. There was no difference between 4 cycles and more than 5 cycles induction chemotherapy. The negative rate of MRD detection by flow cytometry was 17.6% and 38.2% respectively after induction and 3 months after transplantation. The negative rate of MRD gradually increased during the maintenance therapy. The success rate of high dose CTX combined with G-CSF mobilization was 95.5% and transplantation related mortality (TRM) was zero. The median time to progress (TTP) was 75.3 months and the median overall survival (OS) was 99.5 months. TTP of patients obtaining CR and negative MRD after induction were longer that those of no CR and positive MRD. TTP and OS of patients receiving triple-drug induction and ASCT in early stage were longer than those of double-drug induction and ASCT in late stage. LDH≥240 U/L, high risk cytogenetics, ISS II+III stage and HBsAg positive were prognostic factors at diagnosis. However, only MRD and high risk cytogenetics were independent prognostic factors after transplantation and maintenance therapy. The clinical characteristics of patients of TTP ≥6 years were listed below: light-chain type M protein, ISS I stage, normal level of hemoglobin and platelet, normal LDH, HBsAg negative, chromosome 17p-negative, good response and sustained good response. Conclusions: Integrated strategy of bortezomib-based induction regimens followed by ASCT and maintenance therapy can significantly improve the short-term and long-term efficacy. The prognostic factors of TTP in different disease stages were different. Response to treatment, especially MRD, played a more important role in prognostic factors.

[Determination of methyl ethyl ketone in urine by headspace gas chromatography].

Objective: To establish a method for determination of methyl ethyl ketone in urine by headspace gas chromatography. Methods: In the urine sample(hereinafter referred to as urine sample), methyl ethyl ketone is pretreated by headspace technology, and a certain amount of head air is injected into the gas chromatograph, separated by capillary column, detected by hydrogen flame ionization detector, and the retention time is qualitative and the peak height is high. Peak area. Results: Good linearity was in the range of 0.01 to 6.0 µg/ml with a regression equation of y=13.316x+0.8497 and γ=0.9997.The minimum detectable concentration of methyl ethyl ketone was 0.01 µg/ml. The range intra-day RSD and inter-day RSD were 2.2%-5.5% and 2.5%-6.1% respectively. Urine samples can be stored for 20 days in the refrigerator at 4 ℃. Conclusion: The method has a high advantage of sensitivity and accuracy, and also easy to operate. Therefore, it is suitable for the determination of methyl ethyl ketone in urine.

Citrobacter rodentium Induces Tissue-Resident Memory CD4+ T Cells.

Tissue-resident memory T cells (TRM cells) are a novel population of tissue-restricted antigen-specific T cells. TRM cells are induced by pathogens and promote host defense against secondary infections. Although TRM cells cannot be detected in circulation, they are the major memory CD4+ and CD8+ T-cell population in tissues in mice and humans. Murine models of CD8+ TRM cells have shown that CD8+ TRM cells maintain tissue residency via CD69 and though tumor growth factor ß-dependent induction of CD103. In contrast to CD8+ TRM cells, there are few models of CD4+ TRM cells. Thus, much less is known about the factors regulating the induction, maintenance, and host defense functions of CD4+ TRM cells. Citrobacter rodentium is known to induce IL-17+ and IL-22+ CD4+ T cells (Th17 and Th22 cells, respectively). Moreover, data from IL-22 reporter mice show that most IL-22+ cells in the colon 3 months after C. rodentium infection are CD4+ T cells. This collectively suggests that C. rodentium may induce CD4+ TRM cells. Here, we demonstrate that C. rodentium induces a population of IL-17A+ CD4+ T cells that are tissue restricted and antigen specific, thus meeting the criteria of CD4+ TRM cells. These cells expand and are a major source of IL-22 during secondary C. rodentium infection, even before the T-cell phase of the host response in primary infection. Finally, using FTY 720, which depletes circulating naive and effector T cells but not tissue-restricted T cells, we show that these CD4+ TRM cells can promote host defense.

[Determination of diethyl phthalate in the air of workplace by gas chromatography].

Objective: To establish a method for the determination of diethyl phthalate by gas chromatography in the air of workplaces. Methods: Diethyl phthalate in the air of workplace was collected throµgh glass fiber filter, eluted with methylbenzene, and detected by gas chromatography coupled with FID detectors. Results: The linear range of diethyl phthalate determined by this method was 14.0~1 400 µg/ml, y=2.09801x-3.66229, and the coefficient correlation was 0.999 99. The detection limit was 1.10 µg/ml, and the minimum detection concentration was 0.18mg/m(3) (collected sample volume was 30 L) . The within-run precisions were 1.04%~2.75%, and the between-run precisions were 0.34%~1.30%. The recovery rates were 98.72%~103.21%, and sampling efficiency was 97.2%~100.0%. The elution efficiencies were 97.25%~98.68%. The samples could be stored at room temperature for 15 days. Conclusion: The indicators established in this study were conformed with the requirements of GBZ/T210.4-2008, "The Guidelines for the Development of Occupational Hygiene Standards Methods Part 4: Determination of Chemical Substances in the Air of Workplaces" . Diethyl phthalate in the workplace air could be rapidly collected, accurate separated and determinated. This method is applicable to the determination of diethyl phthalate in the workplace air.

[Determination of tributyl phosphate in the air of workplace by gas chromatography].

Objective: To establish a practical method forsampling and detectingtributyl phosphate intheworkplace. Methods: The samples were extracted by glass fiber membrane, eluted with ether, separated by gas chromatography, and detected by flame photometric detector. Results: There were good linear relationship in the minimum detection concentration was 7.2-720.0 µg/ml, and the correlation coefficient was 0.999 92. The detection limit was 0.86 µg/ml, and the minimum detection concentration was 0.14 mg/m(3) (sample volume was 30 L) . Recovery rates were 99.8%-100.2%. The with-in relative standard deviations were 4.0%-5.4% and the between relative standard deviations were 2.0%-5.5%, and average samplingefficiency was about 99.1%-100.0%. Conclusion: This method conforms with the requirements of "Standardization of Methods for Determination of Toxic Substance in Workplace" . Tributyl phosphate in air could be determined accurately using this method.

[Correlation between social support and quality of life in patients with breast cancer at different periods of treatment].

Objective: To analyze the differences between the social support for breast cancer patients and healthy female, and to explore the correlation between social support and quality of life (QOL) in the patients. Methods: From January 2013 to December 2014, 101 patients with operable breast cancer treated at Xinyu City People's Hospital were recruited as the experimental group. They completed questionnaires in the preoperative, postoperative chemoradiotherapy and rehabilitation periods, respectively.101 healthy female volunteers recruited from the community were included as control group, whose age and level of education were matched with those of the experimental group.The general questionnaire including basic information, disease conditions and other projects, perceived social support scale (PSSS), quality of life of breast cancer patients (FACT-B) were applied to evaluate the general situation, social support and QOL of the subjects. The differences in PSSS scores between the experimental and control groups were compared. The correlation between PSSS score and FACT-B score in the experimental group was analyzed. SPSS 18.0 software was used for statistical analysis. Results: The general situations of the experimental and control groups were comparable (all P>0.05). The rates of the total social support score ≥50 in the experimental and control groups were not significantly different (93.6% vs. 94.7%, P=0.067). Compared with that of the control group (23.2±4.8), the scores of family support in the experimental group in preoperative, postoperative chemoradiotherapy and rehabilitation periods were statistically higher (25.6±3.2, 24.2±4.2 and 24.0±3.4, respectively, P=0.034). The social support scores of patients with different demographic characteristics were different. Among the demographic characteristics, years of education and place of residence had the largest impact. The scores of social support in patients with longer education years and living in the urban area were higher than those with shorter education years and living in the rural areas (P<0.001). The scores of QOL among preoperative, postoperative chemoradiotherapy and rehabilitation periods in the experimental group were significantly different (all P<0.05). The patients gained the highest score of QOL in the preoperative period (110.7±5.1) and the lowest in the postoperative chemoradiotherapy period (95.3±18.1). The QOL of patients in the experimental group in preoperative, postoperative chemoradiotherapy and rehabilitation periods were all positively correlated with the overall social support (all P<0.01). Conclusions: The QOL of breast cancer patients at different periods of treatment is positively correlated with the social support. The quality of life can be enhanced by improving the social support for the patients.

[Establishment and application effect appraisement of community chronic obstructive pulmonary disease integrated management system].

Objective: To establish the COPD community integrated management system suitable for our national situation and assess its effects in the prevention and treatment for COPD. Methods: The COPD community integrated management system based on the electronic management system was established, including the functional modules of preliminary screening for COPD, electronic health record, grading management and dual referral system, ect. Two townships were randomly selected from the rural areas in north Guangdong as Observational Community and Control Community, respectively. Resident families were randomly selected from the two communities. One resident aged 40 or higher who was selected randomly from each family was enrolled in the trial and followed up for 2 years.Of a total of 460 participants from the Observational Community, 340 participants accomplished the two-years the follow-up, among whom there were 45 COPD patients, 117 high risk population, 178 common population. Of a total of 380 participants from the Control Community, 212 participants accomplished the follow-up, among whom there were 39 COPD patients, 68 high risk population, 105 common population.According to the COPD community integrated management system, the health cares including preliminary screening for COPD, grading management and dual referral, ect. were implemented in the Observational Community. Essential diagnosis and treatment services were performed in the Control Community. The effects of the system were appraised by comparisons of the pulmonary function change, acute exacerbation, quality of life and change of risk factors, ect. between the two communities. Results: After the intervention, the follow-up rate, smoking-quitting rate, the proportions of decline in current smoking, passive smoking and switching to clean energy for cooking in the Observational Community were significantly greater than those in the Control Community(73.9% vs. 55.8%, 70.8% vs. 9.1%, 24.2% vs. 7.1%, 32.6% vs. 3.5%, 67.8% vs. 3.2%, respectively, P<0.05). COPD knowledge rates of residents in the Observational Community, including "knowing about COPD" , "knowing about the symptoms of COPD" , "Whether COPD can be prevented and treated" and "lung function test" were significantly greater than before (84.7% vs.30.0%, 76.4% vs.7.6%, 71.5% vs.6.8%, 72.1% vs.27.4%, respectively, P<0.05) and greater than those in the Control Community(84.7% vs.73.6%, 76.4% vs.9.4%, 71.5% vs.7.1%, 72.1% vs.32.5%, P<0.05). In the Observational Community, FEV(1) and FEV(1) %Pred were significantly greater than before (1.88±0.71 vs. 1.74±0.64, 75.6±25.0 vs. 69.4±20.5, respectively, P<0.05). The values of the difference before and after the experiment in the patients of GOLD 1 grade COPD in the Observational Community were greater than those in the Control Community(P<0.05). In the Control Community, FEV(1)、FEV(1) %Pred had no significant difference before and after experiment(P>0.05). In the Observational Community, 6MWD, standard treatment rate and exercises>3 days per week were significantly greater than before(550.5±76.0 vs. 474.7±75.9, 64.4% vs. 8.9%, 100% vs. 22.2%, respectively, P<0.05) and greater than those in the Control Community(550.5±76.0 vs. 404.5±56.7, 64.4% vs. 10.3%, 100% vs. 30.8%, respectively, P<0.05), acute exacerbation was significantly less than before (4.4% vs. 17.8%, P<0.05). In the Control Unit, 6MWD was significantly less than before (404.5±56.7 vs. 469.8±58.5, P<0.05). Conclusions: The COPD community integrated management system can play a great role in community integrated prevention for COPD.

TRIM28 interacts with EZH2 and SWI/SNF to activate genes that promote mammosphere formation.

Histone methyl transferase EZH2 (Enhancer of Zeste Homolog 2) is generally associated with H3K27 methylation and gene silencing, as a member of the polycomb repressor 2 (PRC2) complex. Immunoprecipitation and mass spectrometry of the EZH2-protein interactome in estrogen receptor positive, breast cancer-derived MCF7 cells revealed EZH2 interactions with subunits of chromatin remodeler SWI/SNF complex and TRIM28, which formed a complex with EZH2 distinct from PRC2. Unexpectedly, transcriptome profiling showed that EZH2 primarily activates, rather than represses, transcription in MCF7 cells and with TRIM28 co-regulates a set of genes associated with stem cell maintenance and poor survival of breast cancer patients. TRIM28 depletion repressed EZH2 recruitment to chromatin and expression of this gene set, in parallel with decreased CD44hi/CD24lo mammosphere formation. Mammosphere formation, inhibited by EZH2 depletion, was rescued by ectopic expression of EZH2 but not by TRIM28 expression or by EZH2 mutated at the region (pre-SET domain) of TRIM28 interaction. These results support PRC2-independent functions of EZH2 and TRIM28 in activation of gene expression that promotes mammary stem cell enrichment and maintenance.

[PM2.5 from traffic-related ambient air and wood smoke induces epithelial-mesenchymal transition in human bronchial epithelial cells].

Objective: To observe if arterial traffic ambient PM2.5 (TAPM2.5) and wood smoke PM2.5(WSPM2.5) exposure can induce epithelial-mesenchymal transition (EMT) in human bronchial cells (HBEC). Methods: PM2.5 was collected from an arterial traffic road and a typical southern kitchen, and then the collections were extracted by DMSO. The viability of HBEC was measured by Cell Counting Kit (CCK-8) after culture with PM2.5-DMSO extracts for 24 hours. The expressions of EMT markers, including E-cadherin, cytokeratin, α-smooth muscle actin (α-SMA), vimentin and collagen typeⅠ (COL-Ⅰ) in HBEC were assayed by cell immunofluorescence and Western blot analysis after exposed to two different sources of PM2.5-DMSO extracts for 14 days. Results: The cell viability of HBEC increased at low concentrations (1, 2, 10 µg/ml and 1, 5, 10 µg/ml, corresponding to [(118.4±13.7)%, (118.2±8.0)%, (123.0±19.6)% and (112.4±4.1)%, (120±5.4)%, (117.8±7.0)%, respectively, all P<0.05], and then declined at high levels [20, 100, 200 µg/ml and 15, 20, 30, 40 µg/ml, corresponding to (100.7±12.1)%, (53.4±15.3)%, (9.4±1.7)% and (106.8±10.0)%, (93.8±7.9)%, (60.9±9.5)%, (46.2±3.6)%, respectively, P values were 0.923, 0.000, 0.000 and 0.231, 0.278, 0.000, 0.000, respectively] in both TAPM2.5-DMSO and WSPM2.5-DMSO incubation. After exposure for 14 days, the cells lost their typical cobblestone-like shape which implied that EMT might occur. The same treatment caused decreased positive signals of E-cadherin and cytokeratin in a small proportion of the cells. The decreased expressions of cytokeratin were verified by Western blot (TAPM2.5 and WSPM2.5 were 0.063±0.109 and 0.039±0.313, P values were 0.033 and 0.030, respectively), while α-SMA was only significantly upregulated in the WSPM2.5-DMSO group (7.853±4.784, P=0.049). The expressions of E-cadherin decreased in both groups but not statistically significant in Western blot (0.862±0.096 and 0.817±0.212, P values were 0.228 and 0.117, respectively). Another marker of EMT, COL-I, markedly increased in both PM2.5 treatment groups (2.549±1.037 and 3.658±1.207, P values were 0.034 and 0.001). Conclusions: Both PM2.5 from arterial traffic ambient air and wood smoke could induce EMT in human bronchial epithelial cells, while WSPM2.5 appeared to have a more significant influence on EMT in HBEC.