Objective: To investigate the association between edentulism and the risk of social isolation in middle-aged and elderly populations, provide empirical evidence for formulating social isolation prevention and intervention policies targeting edentulous middle-aged and elderly populations. Methods: Data were derived from the baseline survey (2011) and three follow-ups (2013, 2015, 2018) of the China Health and Retirement Longitudinal Study (CHARLS). Participants were enrolled in the follow-up from the baseline. Those identified as socially isolated in any of the follow-up surveys conducted in 2013, 2015, or 2018 were considered to have reached the endpoint; otherwise, the follow-up was continued until the end of the 2018 survey; 9 870 individuals were ultimately included. Subjects were grouped by edentulism status. Chi-square test and multivariate Cox regression analysis were performed using Stata 17.0. Results: During a median follow-up of 6.54 years, 1 800 cases of social isolation occurred, with an incidence rate of 18.23%（17.47%~18.99%）. Multivariate Cox regression showed that edentulism was associated with an increased risk of social isolation (HR=1.21, 95% CI: 1.03-1.42) after adjusting for confounders. Subgroup analysis revealed population heterogeneity. Sensitivity analyses confirmed the stability of the results. Conclusion Edentulism is associated with an increased risk of social isolation in middle-aged and elderly adults.

Objective:To evaluate the performance of high risk human papilloma virus (HR-HPV) E6/E7 mRNA in triaging women with atypical squamous cells of undetermined signification (ASCUS).Methods:The ASCUS cohort determined by liquid-based cytology test in the cervical cancer screening queue in Luoshan County, Xinyang City, Henan Province 2017 were selected. The population underwent colposcopy biopsy and pathological tests, combined with HPV16 or 18 (HPV16/18), HR-HPV DNA and HPV E6/E7 mRNA test. By using the pathological result as the gold standard, the sensitivity, specificity, positive predictor (PPV), negative prediction (NPV), referral rate and 95% confident interval ( CI) of HPV E6/E7 mRNA, HR-HPV DNA, HPV16/18 were calculated, respectively. Results:The average age of 312 ASCUS women was 52.6±7.3 years old. Among the 290 women diagnosed as normal by pathology, 64 (22.1%) were HPV E6/E7 mRNA positive, 86 (29.7%) were HR-HPV DNA positive, and 19 (6.6%) were HPV16/18 positive. All of the cervical intraepithelial neoplasia (CIN) cases determined by pathology were both HPV E6/E7 mRNA and HR-HPV DNA positive. The sensitivity, specificity, PPV, NPV and referral rate of HPV E6/E7 mRNA for predicting CIN2+ lesion in women with ASCUS were 100.0% (95% CI: 72.3, 100.0), 77.8% (95% CI: 72.8, 82.1), 13.0% (95% CI: 7.2, 22.3), 100.0% (95% CI: 98.4, 100.0) and 24.7%. Compared with HPV E6/E7 mRNA, the sensitivity of HR-HPV DNA was similar with HPV E6/E7 mRNA, but with a lower specificity [70.2% (95% CI: 64.8, 75.1), P<0.05], a higher referral rate (32.1%, P<0.05); while HPV 16/18 had a high specificity (93.4%, 95% CI: 90.0, 95.7) and a low sensitivity (30.0%, 95% CI: 10.8, 60.3). Based on the age stratification by age 45, the sensitivity of HPV E6/E7 mRNA in both age groups was 100.0%. The specificity of HPV E6/E7 mRNA in group of ≥45 years was a little higher than that in group of <45 years [79.0% (95% CI: 73.7, 83.5) versus 68.3% (95% CI: 53.0, 80.4)], but the difference was not statistically significant ( P>0.05). Conclusions:The ASCUS woman triaging effect of HPV E6/E7 mRNA detection is better than those of HR-HPV and HPV16/18 under certain conditions. The application of HPV E6/E7 mRNA detection to triage ASCUS population can avoid unnecessary colposcopy referral and reduce the missed diagnosis of cervical lesions.

Objective:To evaluate the performance of high risk human papilloma virus (HR-HPV) E6/E7 mRNA in triaging women with atypical squamous cells of undetermined signification (ASCUS).Methods:The ASCUS cohort determined by liquid-based cytology test in the cervical cancer screening queue in Luoshan County, Xinyang City, Henan Province 2017 were selected. The population underwent colposcopy biopsy and pathological tests, combined with HPV16 or 18 (HPV16/18), HR-HPV DNA and HPV E6/E7 mRNA test. By using the pathological result as the gold standard, the sensitivity, specificity, positive predictor (PPV), negative prediction (NPV), referral rate and 95% confident interval ( CI) of HPV E6/E7 mRNA, HR-HPV DNA, HPV16/18 were calculated, respectively. Results:The average age of 312 ASCUS women was 52.6±7.3 years old. Among the 290 women diagnosed as normal by pathology, 64 (22.1%) were HPV E6/E7 mRNA positive, 86 (29.7%) were HR-HPV DNA positive, and 19 (6.6%) were HPV16/18 positive. All of the cervical intraepithelial neoplasia (CIN) cases determined by pathology were both HPV E6/E7 mRNA and HR-HPV DNA positive. The sensitivity, specificity, PPV, NPV and referral rate of HPV E6/E7 mRNA for predicting CIN2+ lesion in women with ASCUS were 100.0% (95% CI: 72.3, 100.0), 77.8% (95% CI: 72.8, 82.1), 13.0% (95% CI: 7.2, 22.3), 100.0% (95% CI: 98.4, 100.0) and 24.7%. Compared with HPV E6/E7 mRNA, the sensitivity of HR-HPV DNA was similar with HPV E6/E7 mRNA, but with a lower specificity [70.2% (95% CI: 64.8, 75.1), P<0.05], a higher referral rate (32.1%, P<0.05); while HPV 16/18 had a high specificity (93.4%, 95% CI: 90.0, 95.7) and a low sensitivity (30.0%, 95% CI: 10.8, 60.3). Based on the age stratification by age 45, the sensitivity of HPV E6/E7 mRNA in both age groups was 100.0%. The specificity of HPV E6/E7 mRNA in group of ≥45 years was a little higher than that in group of <45 years [79.0% (95% CI: 73.7, 83.5) versus 68.3% (95% CI: 53.0, 80.4)], but the difference was not statistically significant ( P>0.05). Conclusions:The ASCUS woman triaging effect of HPV E6/E7 mRNA detection is better than those of HR-HPV and HPV16/18 under certain conditions. The application of HPV E6/E7 mRNA detection to triage ASCUS population can avoid unnecessary colposcopy referral and reduce the missed diagnosis of cervical lesions.

Objective: This study aimed to evaluate the clinical performance of p16/Ki-67 dual staining for triage high risk HPV (HR-HPV) infected women. Method: Target objects were women who infected HR-HPV and received colposcopy examination between April and December of 2016 at the Second Affiliated Hospital of Zhengzhou University. Gynecologists collected the cervical exfoliated cells from eligible women for p16/Ki-67 dual staining, LBC testing and HPV DNA testing. Histology diagnosis were used as gold standard. Sensitivities, specificities, positive predictive values (PPVs), negative predictive values (NPVs) of p16/Ki-67 dual staining, LBC testing and HPV16/18 testing for triage of HR-HPV positive population were calculated and compared. Results: A total of 295 HR-HPV infected women were selected, and the mean age was (44.29±11.48) years old. Positive rates of p16/Ki-67 dual staining, HPV16/18 testing and LBC testing were 70.17% (207), 56.95% (168) and 85.76% (253), respectively. When CIN2+as the endpoint, among the three triage methods, sensitivity of p16/Ki-67 dual staining was 90.00% (95%CI: 85.06%-93.43%), higher than the value of HPV 16/18 testing, but lower than the value of LBC testing. Specificity, PPV and NPV of p16/Ki-67 dual staining were the highest [71.58% (95%CI: 61.81%-79.67%), 86.96% (95%CI:81.69%-90.88%) and 77.27% (95%CI: 67.49%-84.78%)]. When detection for CIN3+, sensitivity of p16/Ki-67 dual staining was 92.90% (95%CI: 87.74%-95.99%), lower than the value of LBC testing, but higher than the value of HPV16/18 testing. Specificity of p16/Ki-67 dual staining was 55.00% (95%CI: 46.74%-63.00%), lower than the value of HPV16/18 testing, but higher than the value of LBC testing. PPV of p16/Ki-67 dual staining was 69.57% (95%CI: 62.99%-75.43%), lower than the value of HPV 16/18 testing, but higher than the value of LBC testing. NPV of p16/Ki-67 dual staining was 87.50% (95%CI: 78.99%-92.87%), higher than value of HPV 16/18 testing, but lower than the value of LBC testing. Conclusion p16/Ki-67 dual staining has better clinical effects than HPV 16/18 testing and LBC testing for triage women with HR-HPV infection.

Objective: Previous studies have indicated a convergent and bidirectional relationship between metabolic syndrome (MetS) and bipolar disorder (BD). As most of these studies focused mainly on adults diagnosed with BD, our study aims to investigate and characterize metabolic disturbances in child-adolescents diagnosed with BD. Methods: We retrospectively examined the medical records of psychiatric hospitalizations with admitting diagnosis of BD in child-adolescents (age ＜ 18 years). Body mass index (BMI), lipid profile, fasting blood glucose, and blood pressure were primary variables. National Cholesterol Education Program criteria were used to define MetS. Reference group data was obtained from the National Health and Nutrition Examination Survey study. Statistical analyses included t tests, chi-square tests, and Fisher’s exact tests. Results: We identified 140 child-adolescent patients with BD (mean age = 15.12 ± 1.70 years, 53% male). MetS was significantly more common in BD compared to the reference group: 14% (95% confidence interval [95% CI] 8−20) vs. 6.7% (95% CI 4.1−9.2), p = 0.001 with no significant difference by sex. MetS components were higher in the BD group, particularly BMI ≥ 95% (25% vs. 11.8%, p ＜ 0.001) and high blood pressure (17% vs. 8%, p = 0.05). Moreover, female patients had lower odds of high blood pressure (odds ratio = 0.24 [95% CI 0.08−0.69], p = 0.005). Conclusion Compared with the general child-adolescent population, the prevalence of MetS was significantly higher in patients with BD of same age. This reiterates the notion of an increased risk of MetS in patients diagnosed with BD; and thus, further exploration is warranted.

Objective: To investigate the human papillomavirus (HPV) positive rate and its usefulness in predicting CIN2+ in women with atypical squamous cells of undetermined significance (ASC-US) cervical cytology. Methods: A pooled analysis was conducted using published data of hospital classification, HPV positive rate and histopathologic diagnosis in ASC-US population during 2005 to 2017 from 104 studies which enrolled 28 923 ASC-US samples. Results: The overall HPV positive rate was 52.09% (range from 12.06% to 88.68%). The HPV positive rate in 79 tertiary hospitals of 21 244 cases was 52.46%, slightly higher than the 50.87% in 22 second-class hospitals of 6 925 cases. There was no significant difference between specialized hospitals and general hospitals. In addition, the positive rate of HC2 conducted in 66 hospitals with 19 791 cases was 53.13%, which was slightly higher than 51.10% of reverse hybridization from 24 hospitals with 6 338 cases. In 73 studies of 18 163 cases with histological diagnosis, the sensitivity of HPV for detecting CIN2+ was 90.16% (95%CI: 88.91% to 91.28%), specificity was 53.08% (95%CI: 53.02% to 54.57%), positive predictive value was 23.24% and negative predictive value was 97.24%. Conclusion HPV detection is clinically validated for ASC-US triage, but there is a wide variation of HPV positive rate in population of cervical cytological diagnosis as ASC-US in China, suggesting different diagnostic level between regions and hospitals and further improvement is needed.

Objective: To evaluate the feasibility and effectiveness of isothermal human papillomavirus (HPV) DNA amplification test as a primary screening test in the early detection of cervical cancer. Methods: From June to August 2016, 2, 774 women aged 30-64 years old from Inner Mongolia were recruited for cervical cancer screening. HPV DNA was detected by Isomega and cobas4800. INNO-LiPA HPV Genotyping Extra was served as a reference method for the cases whose results were inconsistent by using these two methods. Histological diagnosis was considered as a gold standard to estimate the effectiveness and accuracy of Isomega and cobas4800 for detecting CIN2 or greater. Results: The concordance of Isomega and cobas4800 was 94.84% (Kappa=0.82) for high risk HPV (HR-HPV), 99.68% (Kappa=0.95) for HPV16, 99.78% (Kappa=0.91) for HPV18 and 94.34% (Kappa=0.76) for other HR-HPV types. The concordances of Isomega and the reference were 99.71% (Kappa=0.96), 99.86% (Kappa=0.94) and 96.76% (Kappa=0.87) for HPV16, 18 and other HR-HPV, respectively, while the concordances of cobas4800 and the reference were 99.82% (Kappa=0.97), 99.86% (Kappa=0.94) and 97.51% (Kappa=0.90), respectively. The sensitivity and specificity of Isomega for detecting CIN2+ (including CIN2, CIN3 and squamous cell carcinoma) were 87.76% and 82.94%, respectively, while those of cobas4800 were 89.80% and 85.06%, respectively. Conclusions The concordances of Isomega and cobas4800 is confident. These two methods can accurately detect the HPV16 and 18 genotyping, and have good sensitivity and specificity for clinical diagnosis and population screening of cervical cancer.

Objective: To explore the relationship between high risk HPV (HR-HPV) DNA load and cervical lesions in HR-HPV single/ multiple infections. Methods: Two thousand six hundred and forty-six women from Shanxi, Henan and Xinjiang were recruited into a cervical cancer screening program. Cervical exfoliated cell specimens collected from all of the participants were detected by hybrid capture Ⅱ (HC2), cytological diagnosis was performed according to the Bethesda System, and pathological diagnosis was interpreted using cervical intraepithelial neoplasia (CIN) terminology.Totally 571 cervical specimens were selected and retested to ascertain the HPV types and single/ multiple infections by liner array, a PCR-based method. Semi-quantitative result of HR-HPV DNA load (pg/ml) was estimated by HR HC2.According to the taxonomy of "International Human Papillomavirus Reference Center" , 13 HR-HPVs, including HPV16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59 and 68, which could be detected by HR HC2 were divided into 4 subgroups. Results: The positive rate of HR-HPV in normal cervix (436 cases), CIN1 (88 cases), CIN2+ (47 cases) group were 29.82%, 85.23% and 100%, respectively. The overall prevalence and median viral load increased coordinating with the pathological degree of cervical lesions (P<0.001). The positive rate and viral load of single infection with HR-HPV belongs to α9 species increased coordinating with the pathological degree of cervical lesions (P<0.05). The viral load of single infection with HR-HPV belongs to α7 species in CIN1 group was higher than those of normal group and CIN2+ group, but without statistical significance (P=0.130). The viral load of multiple infections in CIN1 group was 559.13 pg/ml, significantly higher than 37.73 pg/ml of normal histology (P=0.025), but without significant difference of 332.91 pg/ml of CIN2+ group (P=0.790). The median viral load of HPV single infection in CIN1 group was 167.93 pg/ml, significantly lower than 559.73 pg/ml of multiple infections (P=0.044). The incidence of co-infection with HR-HPVs belong to α9 species was 80.56%, dominated in all patterns of multiple infections and their median viral load increased coordinating with the pathological degree of cervical lesions, but without significant difference (P>0.05). The incidence of co-infection with HR-HPVs belong to α7 species was 66.67%, their median viral load in CIN1 group was higher than that of CIN2+ group, but without statistical significance (P>0.05). Conclusions Viral loads of single/ multiple infections with HR-HPVs belong to different species show different tendencies coordinating with the pathological degree of cervical lesions. Women with high grade of cervical lesion were dominantly infected with high viral load of HR-HPVs belong to α9 species, and the viral load of multiple infections is higher than that of single infection in low grade of cervical lesion.

Objective To investigate the human papillomavirus(HPV)positive rate and its usefulness in predicting CIN2+ in women with atypical squamous cells of undetermined significance(ASC?US)cervical cytology. Methods A pooled analysis was conducted using published data of hospital classification,HPV positive rate and histopathologic diagnosis in ASC?US population during 2005 to 2017 from 104 studies which enrolled 28 923 ASC?US samples. Results The overall HPV positive rate was 52.09%(range from 12.06% to 88.68%). The HPV positive rate in 79 tertiary hospitals of 21 244 cases was 52.46%,slightly higher than the 50.87% in 22 second?class hospitals of 6 925 cases. There was no significant difference between specialized hospitals and general hospitals. In addition, the positive rate of HC2 conducted in 66 hospitals with 19 791 cases was 53.13%, which was slightly higher than 51.10% of reverse hybridization from 24 hospitals with 6 338 cases. In 73 studies of 18 163 cases with histological diagnosis, the sensitivity of HPV for detecting CIN2+ was 90.16%(95%CI:88.91% to 91.28%), specificity was 53.08%(95%CI:53.02% to 54.57%),positive predictive value was 23.24% and negative predictive value was 97.24%. Conclusion HPV detection is clinically validated for ASC?US triage, but there is a wide variation of HPV positive rate in population of cervical cytological diagnosis as ASC?US in China, suggesting different diagnostic level between regions and hospitals and further improvement is needed.

Human papillomavirus ( HPV) infection is the necessary cause of cervical cancer. There is a close relationship between the amount of DNA, mRNA and protein expression in the natural history of virus and the cervical lesion. This article is aimed to elaborate the natural history and genital tract distribution of high risk HPV, and also evaluate the HPV based cervical cancer screening technology from the perspective of the natural history of HPV, which is meaningful for screening and clinical practice in devising and utilizing different detection technology.