Objective: To investigate the effect of heterogeneous nuclear ribonucleoprotein K (hnRNP K) and its interaction with human papillomavirus 16 (HPV16) on cervical intraepithelial neoplasia (CIN). Methods: The participants included 67 women with normal cervix (NC), 69 women with CINⅠ and 68 women with CINⅡ/Ⅲ in a community cohort of pathologically diagnosed women established in Jiexiu of Shanxi province, from June 2014 to June 2015. A structured questionnaire was used to collect the demographic data of the subjects and the related factors of cervical lesions. Cervical exfoliated cells and cervical tissues from biopsy or surgery were selected. The infection status of HPV16 was detected by flow-through hybridization. The protein expression levels of hnRNP K were evaluated by Western blot. SPSS 23.0 software was used to collate and analyze the data. To study the differences in demographic characteristics, related factors, hnRNP K protein and HPV16 infection among NC, CINⅠand CINⅡ/Ⅲgroups, χ(2) test, trend χ(2) test, and Kruskal-Wallis H test were conducted. Multiple comparisons of hnRNP K protein in three groups were completed by using the Bonferroni method. The OR and its 95%CI of hnRNP K, HPV16 and CIN were calculated by using the unconditional logistic regression models. Two-way interactions between hnRNP K protein and HPV16 infection on CIN were analyzed by using additive model and related indicators. Results: HPV16 infection rates were 10.4% in women with normal cervix, 14.5% in women with CINⅠ and 41.2% in women with CINⅡ/Ⅲ, respectively. The differences among three groups were significant (P<0.001). Moreover, the infection rates of HPV16 gradually increased with the increasing severity of CIN (trend χ(2)=18.512, P<0.001). The differences in protein expression of hnRNP K among three groups were significant (H=48.138, P<0.001) and the expressionincreased with the development of cervical lesionss (trend χ(2)=21.765, P<0.001). Results from the interaction analysis indicated that there were additive effects between high expression of hnRNP K protein and HPV16 in CINⅡ/Ⅲ group compared with normal group (API=0.639, 95%CI: 0.083-1.196). In contrast, no such additive effect was found in CINⅠ group. Conclusions: HPV16 infection and over-expression of hnRNP K protein were associated with the increased risk of cervical intraepithelial neoplasia. There might be interaction between hnRNP K protein overexpression and HPV16 infection existed on the progress of CINⅡ/Ⅲ.
Case-Control Studies ; Disease Progression ; Female ; Gene Expression Regulation, Neoplastic ; Heterogeneous-Nuclear Ribonucleoprotein K/metabolism* ; Human papillomavirus 16 ; Humans ; Papillomavirus Infections ; Uterine Cervical Neoplasms/virology* ; Uterine Cervical Dysplasia/virology*

Objective: To explore the relationship between abnormal expression of fragile histidine triad (FHIT) gene and methyl-CpG-binding protein 2 (MeCP2) as well as their interaction on cervical cancerization. Methods: A total of 73 patients with cervical squamous cell carcinoma (SCC), 113 patients with cervical intraepithelial neoplasia (CIN Ⅰ, n=45; CINⅡ/Ⅲ, n=68) and 60 women with normal cervix (NC) were included in the study. Real time PCR and Western blot were performed to detect the expression levels of mRNA and protein about FHIT and MeCP2, respectively. The methylation status of FHIT gene CpG island was tested by methylation-specifc PCR (MSP). Kruskal-Wallis H test, χ(2) test, trend χ(2) test and Spearman correlation analysis were conducted with software SPSS 20.0. The interaction was evaluated by generalized multifactor dimensionality reduction (GMDR) model. Results: With the deterioration of cervical lesion, the methylation rates of FHIT gene CpG island (χ(2)=18.64, P<0.001; trend χ(2)=18.08, P<0.001) increased gradually, while the expression levels of FHIT mRNA (H=27.32, P<0.001; trend χ(2)=12.65, P<0.001) and protein (H=47.10, P<0.001; trend χ(2)=29.79, P<0.001) decreased gradually. There was a negative correlation between the methylation rates of FHIT gene CpG island and the expression level of FHIT protein (r=-0.226, P<0.001). The levels of MeCP2 mRNA (H=26.19, P<0.001; trend χ(2)=11.81, P=0.001) and protein (H=69.02, P<0.001; trend χ(2)=47.44, P<0.001) increased gradually with the aggravation of cervical lesions. There was a positive correlation between the expression level of MeCP2 protein and the FHIT mRNA Ct ratio (r=0.254, P<0.001). Expression of proteins were negatively correlated between MeCP2 and FHIT (r=-0.213, P=0.001). The results analyzed by GMDR model showed that there were interactions among high MeCP2 protein expression, the CpG island methylation of FHIT and mRNA and protein expression in CINⅡ/Ⅲ group, and among high MeCP2 mRNA and protein expression, the CpG island methylation of FHIT and low mRNA and protein expression in SCC group. Conclusion: High expression of MeCP2 mRNA and protein, the CpG island methylation and low mRNA and protein expression of FHIT could increase the risk of cervical carcinogenesis, and there might be a synergistic effect on cervical carcinogenesis.
Acid Anhydride Hydrolases/metabolism* ; Carcinoma, Squamous Cell/pathology* ; DNA Methylation ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Methyl-CpG-Binding Protein 2/metabolism* ; Neoplasm Proteins/metabolism* ; Polymerase Chain Reaction/methods* ; RNA, Messenger ; Uterine Cervical Neoplasms/pathology* ; Uterine Cervical Dysplasia/pathology*

Objective: To explore the sampling method in China National Human Biomonitoring Program (HBP) and the related errors, so as to calculate and evaluate the study design in sampling. Methods: The sampling method of HBP is of multistage nature. Taking the results of sampling method from Guizhou province as an example, results related to sampling error and variation coefficient were calculated, using the multistage unequal probability sampling error method. Results: The HBP covered 152 monitoring sites in 31 provinces (autonomous regions and municipalities) and with 21 888 residents selected. The replacement rates at various stages were 5.26%, 6.35% and 40.6% respectively. The sampling error in Guizhou province was 3 207 594, and the coefficient of variation was 0.097. Conclusions: According to the multi-stage unequal probability sampling method, the sampling coefficient variability appeared small with high precision, in Guizhou province. However, this method did not consider the weight adjustment of non-sampling errors such as population missing rate and response rate. Methods related to the calculation on multi-stage sampling error among large-scale public health monitoring projects need to be further studied.
China ; Cities ; Environmental Monitoring ; Humans ; Research Design

Objective To assess the feasibility, efficiency and selectivity of adenovirus-mediated gene transfer to local arterial wall by protein-coated metallic stent. Methods A replication-defective recombinant adenovirus carrying the Lac Z reporter gene for nuclear specific β-galactosidase (Ad-βgal) was used in this study. The coating for metallic stent was made by immersing it in a gelatin solution containing crosslinker. The coated stents were mounted on a 4.0 or 3.0 mm percutaneous transluminal coronary angioplasty (PTCA) balloon and submersed into a high-titer Ad-βgal viral stock (2 × 1010 pfu/ml) for 3 min, and then implanted into the carotid artedes in 4 mini-swines and into the left anterior descending branch of the coronary artery in 2 mini-swines via 8F large lumen guiding catheters. The animals were sacrificed 7 (n=4), 14 (n = 1) and 21 (n = 1 ) days after implantation, respectively. The β-galactosidase expression was assessed by X-gal staining. Results The results showed that the expression of transgene was detected in all animal. In 1 of carotid artery with an intact intima, the β-gal expression was limited to endothelial cells. In vessels with denuded endothelium, gene expression was found in the sub-intima, media and adventitia. The transfection efficiency of medial smooth muscle cells was 38.6%. In 2 animals sacrificed 7 days after transfection, a microscopic examination of X-gal-stained samples did not show evidence of transfection in remote organs and arterial segments adjacent to the treated arterial site. Conclusions Adenovirus-mediated arterial gene transfer to endothelial, smooth muscle cells and adventitia by protein-coated metallic stent is feasible. The transfection efficiency is higher. The coated stent may act as a good carrier of adenovirus-mediated gene transfer and have a potential to prevent restenosis following PTCA.

OBJECTIVEFurther studies have been conducted to evaluate the roles of Ngn3 in adult islet maintenance and renewal.

METHODSIslets were isolated from 6 - 8 week old male C57BL/6 mice. After common bile duct cannulation, the pancreas was resected and digested in collagenase V (2.5 mg/ml). Islets were then handpicked and 10 - 12 islets were plated in 60 mm culture dish and cultivated with RPMI-1640, which contained 12.5 mmol/L HEPES, 5.2 mmol/L glucose and 2% fetal bovine serum (FBS). Islet cells were analyzed by immunocytochemistry methods for A6, insulin, glucagon, nestin, Ngn3 and 5-bromo-2'-deoxy-uridine (BrdU).

RESULTSThe results of these studies indicated that less than 15 percent of proliferated islet cells were Ngn3 expressing cells, in which about one third of the Ngn3 positive cells co-expressed A6. The existence of Ngn3 in cultured islet cells is consistent with the results from other's findings both in embryogenesis and adult islet studies. A significant finding of our study is that the existence of A6 and Ngn3 co-expressing cells in the cultured islet. A6 is a marker for identifying bile duct epithelial cell oriented hepatic progenitor cells. Islet-derived A6 cells are possibly born in the adult pancreatic duct and migrate into islets. A6 cells co-express Ngn3 when these cells commit to endocrine lineage within the islets. More interestingly, islet-derived A6 positive cells have the potential to transdifferentiate into hepatic cells.

CONCLUSIONThe presence of Ngn3(+) and A6(+) cells in the cultured islets suggests that the four established islet cell types arise from a common endocrine lineage residing within the adult islets. A6 and Ngn3 are useful markers for understanding intra-islet adult stem cell lineages in our future studies. This approach may allow for significant advances in understanding the IPC proliferation and differentiation, and open the possibility of using intra-islet adult stem cells for diabetes treatment.

Animals ; Basic Helix-Loop-Helix Transcription Factors ; Cell Differentiation ; Cell Lineage ; Cells, Cultured ; Islets of Langerhans ; cytology ; Male ; Mice ; Mice, Inbred C57BL ; Microfilament Proteins ; Nerve Tissue Proteins ; biosynthesis ; Protein-Tyrosine Kinases ; biosynthesis ; Stem Cells ; cytology ; metabolism

Background: Both intra-abdominal fat (IAF) and high-density lipoprotein cholesterol (HDL-C) are known to be associated with cardiometabolic health. We evaluated whether the accumulation of computed tomography (CT)-measured IAF over 5 years was related to baseline HDL-C concentration in a prospective cohort study. Methods: All participants were Japanese-Americans between the ages of 34 and 74 years. Plasma HDL-C concentration and CT measurements of IAF, abdominal subcutaneous fat (SCF), and thigh SCF cross-sectional areas were assessed at baseline and at 5-year follow-up visits. Results: A total of 397 subjects without diabetes were included. The mean±standard deviation HDL-C concentration was 51.6±13.0 mg/dL in men and 66.0±17.0 mg/dL in women, and the IAF was 91.9±48.4 cm2 in men and 63.1±39.5 cm2 in women. The baseline plasma concentration of HDL-C was inversely associated with the change in IAF over 5 years using multivariable regression analysis with adjustment for age, sex, family history of diabetes, weight change over 5 years, and baseline measurements of body mass index, IAF, abdominal SCF, abdominal circumference, thigh SCF, and homeostatic model assessment for insulin resistance. Conclusion These results demonstrate that HDL-C concentration significantly predicts future accumulation of IAF over 5 years independent of age, sex, insulin sensitivity, and body composition in Japanese-American men and women without diabetes.

Background: Both intra-abdominal fat (IAF) and high-density lipoprotein cholesterol (HDL-C) are known to be associated with cardiometabolic health. We evaluated whether the accumulation of computed tomography (CT)-measured IAF over 5 years was related to baseline HDL-C concentration in a prospective cohort study. Methods: All participants were Japanese-Americans between the ages of 34 and 74 years. Plasma HDL-C concentration and CT measurements of IAF, abdominal subcutaneous fat (SCF), and thigh SCF cross-sectional areas were assessed at baseline and at 5-year follow-up visits. Results: A total of 397 subjects without diabetes were included. The mean±standard deviation HDL-C concentration was 51.6±13.0 mg/dL in men and 66.0±17.0 mg/dL in women, and the IAF was 91.9±48.4 cm2 in men and 63.1±39.5 cm2 in women. The baseline plasma concentration of HDL-C was inversely associated with the change in IAF over 5 years using multivariable regression analysis with adjustment for age, sex, family history of diabetes, weight change over 5 years, and baseline measurements of body mass index, IAF, abdominal SCF, abdominal circumference, thigh SCF, and homeostatic model assessment for insulin resistance. Conclusion These results demonstrate that HDL-C concentration significantly predicts future accumulation of IAF over 5 years independent of age, sex, insulin sensitivity, and body composition in Japanese-American men and women without diabetes.

Identification of prognosis-related risk factors and accurate assessment of risk stratification in patients with gastrointestinal stromal tumor (GIST) is of great significance not only for establishing a reliable prognostic model and developing a follow-up plan but also for selecting potential populations benefiting from neoadjuvant therapies. Although several risk stratification models have been established, it is still challenging to accurately assess patients' risk of recurrence, and the performance of these prediction models still needs to be improved. This review focused on the latest studies in recurrence risk assessment for GIST patients, and summarized potential predictive markers and recurrence risk models related to tumor-related characteristic parameters, novel laboratory examinations, radiological imaging signatures and molecular pathological features, which could provide a reference for accurate risk stratification and individualized targeted therapies for GIST patients.
Humans ; Gastrointestinal Stromal Tumors/surgery* ; Risk Assessment ; Prognosis ; Risk Factors ; Neoplasm Recurrence, Local ; Retrospective Studies

Background: We describe the association between high density lipoprotein cholesterol (HDL-C) concentration and computed tomography (CT)-measured fat depots. Methods: We examined the cross-sectional associations between HDL-C concentration and intra-abdominal (IAF), abdominal subcutaneous (SCF), and thigh fat (TF) areas in 641 Japanese-American men and women. IAF, SCF, and TF were measured by CT at the level of the umbilicus and mid-thigh. The associations between fat area measurements and HDL-C were examined using multivariate linear regression analysis adjusting for age, sex, diabetes family history, homeostasis model assessment of insulin resistance (HOMA-IR), and body mass index (BMI). Non-linearity was assessed using fractional polynomials. Results: Mean±standard deviation of HDL-C concentration and IAF in men and women were 1.30±0.34 mg/dL, 105±55.3 cm2, and 1.67±0.43 mg/dL, 74.4±46.6 cm2 and differed significantly by gender for both comparisons (P<0.001). In univariate analysis, HDL-C concentration was significantly associated with CT-measured fat depots. In multivariate analysis, IAF was significantly and non-linearly associated with HDL-C concentration adjusted for age, sex, BMI, HOMA-IR, SCF, and TF (IAF: β=–0.1012, P <0.001; IAF2: β=0.0008, P<0.001). SCF was also negatively and linearly associated with HDL-C (β=–0.4919, P=0.001). Conclusion HDL-C does not linearly decline with increasing IAF in Japanese-Americans. A more complex pattern better fits this association.

Objective: To understand the related risk behaviors, knowledge and status of HIV/AIDS infection among rural adults of Derung minority, to provide relevant messages for the development of HIV/AIDS intervention strategy in this minority group. Methods: We used system sampling method to conduct a cross-sectional survey in 6 administration villages of Derung Township, Gongshan Derung and Nu Autonomous County in Nujiang Lisu Autonomous Prefecture of Yunnan Province, with a sample size estimated as 383. Adult residents with Derung minority in six villages of Gongshan County were involved, with relevant information collected through door-to-door visit. HIV antibody was tested and SPSS 17.0 was used for statistical analysis. Results: Information on 394 valid respondents was collected, with age as between 18 and 65 (34.39±9.74), 80.7% (318/394) as married, 54.0% (213/394) having had primary school education, 13.2% (52/394) as migrant workers. In this population, the overall HIV infection rate appeared as 0.5% (2/400), mainly through sexually transmission. The rate of awareness on HIV/AIDS was 69.8% (275/394), mainly through free publicized materials 50.0% (197/394). Rates on premarital sexual behavior on multiple sexual partners in the past year, on temporary sexual partners in the past year, having commercial sexual experiences in the past year and ever used condoms when engaging in casual sex, were 6.4% (60/366), 18.0%(66/366), 5.7%(21/366), 1.9%(7/366) and 8.0%(25/311), respectively. Conclusions: Few numbers of HIV infections were identified among the migrating workers with Derung minority, with sexual transmission as the major route, along with the increased number of rural migrant workers and the low rates both on AIDS knowledge and condom use, accompanied by the high risk sexual behavior appeared in this rural adult residents of Derung minority. Relative strategies on HIV/AIDS intervention and control should be developed.
Acquired Immunodeficiency Syndrome ; Adult ; China/epidemiology* ; Condoms ; Cross-Sectional Studies ; HIV Infections/epidemiology* ; Health Knowledge, Attitudes, Practice ; Humans ; Infections ; Risk-Taking ; Rural Population/statistics & numerical data* ; Sexual Behavior ; Sexual Partners ; Surveys and Questionnaires ; Transients and Migrants