1.Synthesis and identification of RGD-modified tumstatin peptide 19 and its inhibitory effect on proliferation, migration, and invasion of liver cancer SK-Hep-1 cells
WANG Shun1a,2 ; YU Jiaqi1b ; HU Yue1a ; ZHAO Zhenglin1a ; NIU Shudong1c ; JIA Di1a ; YANG Chao1a ; YI Tonghui1d ; LI Shuyan1a
Chinese Journal of Cancer Biotherapy 2024;31(9):849-856
		                        		
		                        			
		                        			[摘  要]  目的:探讨精氨酸-甘氨酸-天冬氨酸(RGD)修饰对肿瘤抑素19肽(T-19)抗肝癌活性的影响,比较分析T-19及RGD修饰的T-19(RGD-T-19)对肝癌SK-Hep-1细胞增殖、侵袭和迁移能力的影响。方法:用Fmoc固相法合成T-19及RGD-T-19,用高效液相色谱仪和质谱进行分离、鉴定。常规培养SK-Hep-1细胞,用0、50、100、150、200、250 mg/mL的T-19及RGD-T-19分别处理细胞,分为0 mg/mL(对照)组、50 mg/mL组、100 mg/mL组、150 mg/mL组、200 mg/mL组、250 mg/mL组。CCK-8法、克隆形成实验、划痕愈合实验和Tanswell小室实验、WB法和qPCR法分别检测SK-Hep-1细胞的增殖、迁移、侵袭能力,以及环氧合酶-2(COX-2)、基质金属蛋白酶-2(MMP-2)、MMP-9、组织基质金属蛋白酶抑制剂-1(TIMP-1)、TIMP-2蛋白和MMP-1、MMP-2 mRNA的表达。结果:经质谱鉴定,用Fmoc固相法合成的T-19及RGD-T-19纯度高。T-19和RGD-T-19均能显著抑制SK-Hep-1细胞的增殖、迁移、侵袭能力,抑制COX-2蛋白、MMP-2和MMP-9蛋白及mRNA的表达、促进TIMP-1、TIMP-2蛋白的表达(P < 0.05, P < 0.01, P < 0.001),RGD-T-19的抑制或促进效应均明显强于T-19(均P < 0.05)。结论:利用Fmoc固相法合成了纯度高、活性好的T-19及RGD-T-19,两种肽均能抑制SK-Hep-1细胞增殖、侵袭和迁移能力,RGD-T-19作用明显强于T-19。
		                        		
		                        		
		                        		
		                        	
2.Nodal T-follicular helper cell lymphoma, angioimmunoblastic-type associated with diffuse large B-cell lymphoma: a clinicopathological study.
G N WANG ; W G ZHAO ; D D ZHANG ; Y P ZHANG ; E J LIU ; S S LU ; W C LI
Chinese Journal of Pathology 2023;52(9):918-923
		                        		
		                        			
		                        			Objective: To investigate the clinicopathological features and molecular genetics of diffuse large B-cell lymphomas (DLBCL) with concurrent or secondary to nodal T-follicular helper cell lymphoma, angioimmunoblastic-type (nTFHL-AI). Methods: The clinicopathological features and molecular genetics of DLBCL associated with nTFHL-AI diagnosed between January 2015 and October 2022 at the First Affiliated Hospital of Zhengzhou University were analyzed using histology, immunohistochemistry, PCR, EBV-encoded RNA in situ hybridization and fluorescence in situ hybridization (FISH). Clinical information was collected and analyzed. Results: A total of 6 cases including 3 nTFHL-AI with secondary DLBCL and 3 composite lymphomas were reviewed. There were 4 male and 2 female patients, whose ages ranged from 40 to 74 years (median 57 years). All patients presented with nodal lesions at an advanced Ann Arbor stage Ⅲ/Ⅳ (6/6). Bone marrow involvement was detected in 4 patients. All cases showed typical histologic and immunophenotypic characteristics of nTFHL-AI. Among them, 5 cases of DLBCL with concurrent nTFHL-AI exhibited numerous large atypical lymphoid cells and the tumor cells were CD20 and CD79α positive. The only case of DLBCL secondary to nTFHL-AI showed plasma cell differentiation and reduced expression of CD20. All of cases were activated B-cell (ABC)/non-germinal center B-cell (non-GCB) subtype. Three of the 6 cases were EBV positive with>100 positive cells/high power field, meeting the diagnostic criteria of EBV+DLBCL. The expression of MYC and CD30 protein in the DLBCL region was higher than that in the nTFHL-AI region (n=5). C-MYC, bcl-6 and bcl-2 translocations were not detected in the 4 cases that were subject to FISH. Four of the 6 patients received chemotherapy after diagnosis. For the DLBCL cases of nTFHL-AI with secondary DLBCL, the interval was between 2-20 months. During the follow-up period ranging from 3-29 months, 3 of the 6 patients died of the disease. Conclusions: DLBCL associated with nTFHL-AI is very rare. The expansion of EBV-infected B cells in nTFHL-AI may progress to secondary EBV+DLBCL. However, EBV-negative cases have also been reported, suggesting possible other mechanisms. The up-regulation of MYC expression in these cases suggests a possible role in B-cell lymphomagenesis. Clinicians should be aware that another biopsy is still necessary to rule out concurrent or secondary DLBCL when nodal and extranodal lesions are noted after nTFHL-AI treatment.
		                        		
		                        		
		                        		
		                        			Female
		                        			;
		                        		
		                        			Male
		                        			;
		                        		
		                        			Humans
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		                        			In Situ Hybridization, Fluorescence
		                        			;
		                        		
		                        			Lymphoma, Large B-Cell, Diffuse
		                        			;
		                        		
		                        			B-Lymphocytes
		                        			;
		                        		
		                        			Biopsy
		                        			;
		                        		
		                        			T-Lymphocytes, Helper-Inducer
		                        			
		                        		
		                        	
4.Development and validation of a prognostic prediction model for patients with stage Ⅰ to Ⅲ colon cancer incorporating high-risk pathological features.
K X LI ; Q B WU ; F Q ZHAO ; J L ZHANG ; S L LUO ; S D HU ; B WU ; H L LI ; G L LIN ; H Z QIU ; J Y LU ; L XU ; Z WANG ; X H DU ; L KANG ; X WANG ; Z Q WANG ; Q LIU ; Y XIAO
Chinese Journal of Surgery 2023;61(9):753-759
		                        		
		                        			
		                        			Objective: To examine a predictive model that incorporating high risk pathological factors for the prognosis of stage Ⅰ to Ⅲ colon cancer. Methods: This study retrospectively collected clinicopathological information and survival outcomes of stage Ⅰ~Ⅲ colon cancer patients who underwent curative surgery in 7 tertiary hospitals in China from January 1, 2016 to December 31, 2017. A total of 1 650 patients were enrolled, aged (M(IQR)) 62 (18) years (range: 14 to 100). There were 963 males and 687 females. The median follow-up period was 51 months. The Cox proportional hazardous regression model was utilized to select high-risk pathological factors, establish the nomogram and scoring system. The Bootstrap resampling method was utilized for internal validation of the model, the concordance index (C-index) was used to assess discrimination and calibration curves were presented to assess model calibration. The Kaplan-Meier method was used to plot survival curves after risk grouping, and Cox regression was used to compare disease-free survival between subgroups. Results: Age (HR=1.020, 95%CI: 1.008 to 1.033, P=0.001), T stage (T3:HR=1.995,95%CI:1.062 to 3.750,P=0.032;T4:HR=4.196, 95%CI: 2.188 to 8.045, P<0.01), N stage (N1: HR=1.834, 95%CI: 1.307 to 2.574, P<0.01; N2: HR=3.970, 95%CI: 2.724 to 5.787, P<0.01) and number of lymph nodes examined (≥36: HR=0.438, 95%CI: 0.242 to 0.790, P=0.006) were independently associated with disease-free survival. The C-index of the scoring model (model 1) based on age, T stage, N stage, and dichotomous variables of the lymph nodes examined (<12 and ≥12) was 0.723, and the C-index of the scoring model (model 2) based on age, T stage, N stage, and multi-categorical variables of the lymph nodes examined (<12, 12 to <24, 24 to <36, and ≥36) was 0.726. A scoring system was established based on age, T stage, N stage, and multi-categorical variables of lymph nodes examined, the 3-year DFS of the low-risk (≤1), middle-risk (2 to 4) and high-risk (≥5) group were 96.3% (n=711), 89.0% (n=626) and 71.4% (n=313), respectively. Statistically significant difference was observed among groups (P<0.01). Conclusions: The number of lymph nodes examined was an independent prognostic factor for disease-free survival after curative surgery in patients with stage Ⅰ to Ⅲ colon cancer. Incorporating the number of lymph nodes examined as a multi-categorical variable into the T and N staging system could improve prognostic predictive validity.
		                        		
		                        		
		                        		
		                        			Male
		                        			;
		                        		
		                        			Female
		                        			;
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Prognosis
		                        			;
		                        		
		                        			Neoplasm Staging
		                        			;
		                        		
		                        			Retrospective Studies
		                        			;
		                        		
		                        			Nomograms
		                        			;
		                        		
		                        			Lymph Nodes/pathology*
		                        			;
		                        		
		                        			Risk Factors
		                        			;
		                        		
		                        			Colonic Neoplasms/surgery*
		                        			
		                        		
		                        	
5.miR-185 inhibits the proliferation and migration of osteosarcoma MG63 cells via regulating CDC42 gene expression
WANG Leia ; QIU Mingxianb, ; ZHANG Huironga ; ZHANG Jinpingc ; ZHAO Jingd ; KANG Xiaob
Chinese Journal of Cancer Biotherapy 2022;29(2):114-119
		                        		
		                        			
		                        			[Abstract]  Objective: To analyze the expression of miR-185 and cell division cyclin 42 (CDC42) in osteosarcoma tissues and cells, and to preliminarily explore whether miR-185 affects the proliferation and migration of osteosarcoma MG63 cells by regulating CDC42. Methods: The cancer tissues and para-cancerous tissues of 28 patients with osteosarcoma that pathologically confirmed in the Fourth People's Hospital of Hengshui City from January 2020 to January 2021 were collected for this study. Immunohistochemistry was used to detect the expression of CDC42 in osteosarcoma tissues, and qPCR was used to detect the expression of miR-185 in osteosarcoma tissues. Dual-luciferase reporter gene experiment was applied to verify the targeting relationship between CDC42 and miR-185. According to different transfectants, MG63 cells were divided into miR-185 mimic group, miR-NC group, miR-185 inhibitor group, NC-inhibitor group, CDC42 group (transfected with CDC42 over-expression vector), and negative control (NC) group. The effects of miR-185 and CDC42 expression on the migration, proliferation and cell cycle of MG63 cells were detected by scratch healing assay, CCK-8 method and FCM, respectively. A nude mouse xenograft model was constructed by inoculating osteosarcoma MG63 cells. Immunohistochemistry, qPCR and WB methods were used to detect the effects of over-expression or knock-down of miR-185 on the expression of Ki67 and CDC42 in transplanted tumor tissues. Results: Compared with para-cancerous tissues, the expression of miR-185 in osteosarcoma tissues was significantly decreased, while the expression of CDC42 was significantly increased (all P<0.01). CDC42 was verified to be a target gene of miR-185. Compared with the control group, the migration and proliferation of MG63 cells in the miR-185 mimic group were inhibited (all P<0.01), while the migration and proliferation of MG63 cells in the CDC42 group were increased and the cell cycle was arrested in the S phase (all P<0.01). Compared with the miR-185 group, the migration and proliferation abilities of MG63 cells in the miR-185+CDC42 group were promoted, and the proportion of cells in S phase was increased (all P<0.01). Compared with the control group, the expression of Ki67 and CDC42 in the transplanted tumor tissues of miR-185 mimic group was significantly decreased (all P<0.01), while the opposite results were observed in miR-185 inhibitor group (all P<0.01). Conclusion: miR-185 is lowly expressed while CDC42 is highly expressed in osteosarcoma tissues. miR-185 can inhibit the proliferation and migration of osteosarcoma MG63 cells by negatively regulating the expression of CDC42.
		                        		
		                        		
		                        		
		                        	
8.Stratified sampling survey of major human parasitic diseases in Henan province.
B L XU ; H W ZHANG ; Y DENG ; Z L CHEN ; W Q CHEN ; D L LU ; Y L ZHANG ; Y L ZHAO ; X M LIN ; Q HUANG ; C Y YANG ; Y LIU ; R M ZHOU ; P LI ; J S CHEN ; L J HE ; D QIAN
Chinese Journal of Epidemiology 2018;39(3):322-328
		                        		
		                        			
		                        			Objective: To understand the prevalence of major human parasitic diseases and related factors in Henan province. Methods: This stratified sampling survey was carried out according to the requirement of national survey protocol of major human parasitic diseases, 2014-2015. The prevalence of soil-transmitted helminths infection, taeniasis and intestinal protozoiasis were surveyed in 104 sites selected from 35 counties (districts) and the prevalence of clonorchiasis was surveyed in 62 sites selected from 37 townships. In each survey spot, 250 persons were surveyed. A total of 26 866 persons and 15 893 persons were surveyed. Modified Kato-Katz thick smear was used to detect the eggs of intestinal helminthes. Tube fecal culture was used to identify the species of hookworm. The Enterobius eggs were detected in children aged 3 to 6 years by using adhesive tape. The cyst and trophozoite of intestinal protozoa were examined with physiological saline direct smear method and iodine stain method. Results: The overall infestation rate of intestinal parasites was2.02% in Henan, and the worm infection rate was higher than protozoa infection rate. Fourteen kinds of intestinal parasites were found, including nematode (5 species), trematode (2 species), and protozoan (7 species). The infection rate of Enterobius vermicularis was highest, and Qinba Mountain ecological area had the highest infestation rate of intestinal parasites in 4 ecological areas of Henan. There was no significant difference in intestinal parasite infection rate between males and females (χ(2)=3.630, P=0.057), and the differences in intestinal parasite infection rate among different age groups had significance (χ(2)=124.783, P=0.000 1). The infection rate reached the peak in age group ≤9 years and the major parasite was Enterobius vermicularis. Furthermore the overall human infection rate of parasite showed a downward trend with the increase of educational level of the people (χ(2)=70.969, P=0.000 1), the differences had significance (χ(2)=120.118, P=0.000 1). For different populations, the infection rate of intestinal parasites was highest among preschool children. The infection of intestinal helminth was mainly mild, only 2 severe cases were detected. The infection rate of Clonorchis sinensis in urban residents was only 0.006%. Logistic regression analysis showed that being preschool children (χ(2)=15.765, P=0.000 1) and drinking well water (χ(2)=45.589, P=0.000 1) were the risk factors for intestinal parasite infection, and annual income per capita of farmers was the protective factor against intestinal parasite infection. The infection rates of protozoa and intestinal parasites decreased sharply compared with the results of previous two surveys, and the rate of intestinal helminth infection also dropped sharply compared with the second survey. The numbers of protozoa, helminth and intestinal parasites detected in this survey were all less than the numbers found in the previous two surveys. Conclusions: Compared the results of three surveys in Henan, the infection rate of protozoa and intestinal parasites showed a downward trend. The prevention and treatment of Enterobius vermicularis infection in children should be the key point of parasitic disease control in the future.
		                        		
		                        		
		                        		
		                        			Animals
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		                        			Child
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		                        			Child, Preschool
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		                        			Clonorchiasis/epidemiology*
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		                        			Farmers
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		                        			Feces/parasitology*
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		                        			Female
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		                        			Helminthiasis/epidemiology*
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		                        			Helminths
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		                        			Humans
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		                        			Intestinal Diseases, Parasitic/parasitology*
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		                        			Male
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		                        			Prevalence
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		                        			Protective Factors
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		                        			Risk Factors
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		                        			Rural Population
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		                        			Soil Microbiology
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		                        			Surveys and Questionnaires
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		                        			Taeniasis/epidemiology*
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		                        			Trematode Infections/parasitology*
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		                        			Urban Population
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		                        			Water Wells
		                        			
		                        		
		                        	
9.Trends in 30-day case fatality rate in patients hospitalized due to acute myocardial infarction in Beijing, 2007-2012.
J Y SUN ; Q ZHANG ; D ZHAO ; M WANG ; S GAO ; X Y HAN ; J LIU
Chinese Journal of Epidemiology 2018;39(3):363-367
		                        		
		                        			
		                        			Objective: To understand the distribution and trends in 30-day coronary heart disease (CHD) case fatality rate in patients hospitalized due to acute myocardial infarction (AMI) in Beijing during 2007-2012. Methods: The clinical data of patients hospitalized due to AMI in Beijing from 1 January 2007 to 31 December 2012 were collected from "The Cardiovascular Disease Surveillance System in Beijing" . A total of 77 943 local patients aged ≥25 years were hospitalized due to AMI in Beijing during the this period. After excluding duplicate records and validation for the completeness and accuracy of the records, the clinical characteristics of the patients and 30-day CHD case fatality rate in the patients were analyzed. Trends in 30-day CHD case fatality rate in the patients were analyzed with Poisson regression models. Results: The age-standardized average 30-day CHD case fatality rate was 9.7% in the 77 943 patients. During this period, a decreasing trend was observed in 30-day CHD case fatality rate after adjusting for age and gender (P<0.001). The age-standardized 30-day CHD case fatality rate decreased by 16.0%, from 10.8% in 2007 to 9.0% in 2012. The decreases of 30-day CHD case fatality rates were noted in both men and women, whereas 30-day CHD case fatality rate was higher in women (14.1%) than in men (7.6%) after adjusting for age. During this period, the proportion of ST-segment elevation myocardial infarction (STEMI) decreased, while the proportion of non-ST-segment elevation myocardial infarction (NSTEMI) increased with year. A significant decline (20.1%) in 30-day case fatality rate of STEMI was found, but no decline was found for 30-day mortality rate of NSTEMI. Conclusion: A decreasing trend in 30-day CHD case fatality rate was observed in the patients aged ≥25 years and hospitalized due to AMI in Beijing during 2007-2012, indicating the improvement in short-term prognosis of patients hospitalized due to AMI. Our findings highlight the urgent need to improve the treatment for woman and NSTEMI patients.
		                        		
		                        		
		                        		
		                        			Acute Disease
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		                        			Adult
		                        			;
		                        		
		                        			Aged
		                        			;
		                        		
		                        			Aged, 80 and over
		                        			;
		                        		
		                        			Beijing/epidemiology*
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		                        			Coronary Disease/mortality*
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		                        			Female
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		                        			Hospital Mortality
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		                        			Hospitalization/trends*
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		                        			Humans
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		                        			Male
		                        			;
		                        		
		                        			Middle Aged
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		                        			Myocardial Infarction/mortality*
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		                        			Prognosis
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		                        			Survival Analysis
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		                        			Time Factors
		                        			
		                        		
		                        	
10.Age-related modification effect on the association between body mass index and the risk of hypertension: A Cohort Study on Chinese people living in the rural areas.
D D ZHANG ; X J LIU ; B Y WANG ; Y C REN ; Y ZHAO ; F Y LIU ; D C LIU ; C CHENG ; X CHEN ; L L LIU ; Q G ZHOU ; Q H XU ; Y H XIONG ; J L LIU ; Z Y YOU ; M ZHANG ; D S HU
Chinese Journal of Epidemiology 2018;39(6):765-769
		                        		
		                        			
		                        			Objective: To study the modification effect of age on the association between body mass index and the risk of hypertension. Methods: People age ≥18 years old were selected by clusters, from a rural area of Henan province. In total, 20 194 people were recruited at baseline during 2007 and 2008, and the follow-up study was completed from 2013 to 2014. Logistic regression model was used to assess the risk of incident hypertension by baseline BMI and age-specific BMI. Results: During the 6-year follow-up period, 1 950 hypertensive persons were detected, including 784 men and 1 166 women, with cumulative incidence rates as 19.96%, 20.51%, and 19.61%, respectively. Compared with those whose BMI<22 kg/m(2), the RRs of hypertension were 1.09 (0.93-1.27), 1.17 (1.01-1.37), 1.34 (1.14-1.58) and 1.31 (1.09-1.56) for participants with BMI as 22-, 24-, 26- and ≥28 kg/m(2), respectively. In young and middle-aged populations, the risk of hypertension gradually increased with the rise of BMI (trend P<0.05). However, in the elderly, the increasing trend on the risk of hypertension risk was not as significantly obvious (trend P>0.05). Conclusion: The effect of BMI on the incidence of hypertension seemed to depend on age. Our findings suggested that a weight reduction program would be more effective on young or middle-aged populations, to prevent the development of hypertension.
		                        		
		                        		
		                        		
		                        			Adolescent
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		                        			Age Factors
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		                        			Aged
		                        			;
		                        		
		                        			Asian People/statistics & numerical data*
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		                        			Body Mass Index
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		                        			Cohort Studies
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		                        			Female
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		                        			Follow-Up Studies
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		                        			Humans
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		                        			Hypertension/ethnology*
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		                        			Incidence
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		                        			Logistic Models
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		                        			Male
		                        			;
		                        		
		                        			Middle Aged
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		                        			Risk Factors
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		                        			Rural Population
		                        			
		                        		
		                        	
            
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