High expression of CETN2 is associated with platinum resistance and poor prognosis in epithelial ovarian cancer

Purpose The poor prognosis of ovarian cancer is largely due to platinum resistance. It has been demonstrated that nucleotide excision repair (NER) involving centrin-2(CETN2) is connected to platinum resistance in ovarian cancer. The molecular mechanism of CETN2 in ovarian cancer and the mechanism affecting the outcome of chemotherapy are unknown. Methods The protein–protein interaction (PPI) network was mapped after obtaining the interacting proteins of CETN2, and the interacting genes were subjected to enrichment analysis. To examine the relationship between CETN2 and platinum resistance, gene microarray data and clinical data related to platinum resistance in ovarian cancer were downloaded. The possible signaling pathway of CETN2 was investigated by Gene set enrichment analysis (GSEA). Immune infiltration analysis was performed. Immunohistochemistry (IHC) and quantitative real-time PCR (QRT-PCR) were used to examine the expression of CETN2 in clinical samples in relation to the effectiveness of chemotherapy. The capacity of CETN2 to predict chemotherapy results was proven by receiver operating characteristic (ROC) curves after the construction of two prediction models, the logistic regression model and the decision tree model. The impact of CETN2 on prognosis was examined using the Kaplan–Meier technique. Result CETN2 was associated with NER, oxidative phosphorylation (OXPHOS) and cell cycle pathways in ovarian cancer drug-resistant samples. In clinical samples, CETN2 showed its possible correlation with immune infiltration. The protein expression level of CETN2 was significantly higher in platinum-resistant patients than that in platinum-sensitive patients, and the expression level had some predictive value for chemotherapy outcome, and high CETN2 protein expression was associated with poorer progression-free survival (AU)

High expression of CETN2 is associated with platinum resistance and poor prognosis in epithelial ovarian cancer.

PURPOSE: The poor prognosis of ovarian cancer is largely due to platinum resistance. It has been demonstrated that nucleotide excision repair (NER) involving centrin-2(CETN2) is connected to platinum resistance in ovarian cancer. The molecular mechanism of CETN2 in ovarian cancer and the mechanism affecting the outcome of chemotherapy are unknown. METHODS: The protein-protein interaction (PPI) network was mapped after obtaining the interacting proteins of CETN2, and the interacting genes were subjected to enrichment analysis. To examine the relationship between CETN2 and platinum resistance, gene microarray data and clinical data related to platinum resistance in ovarian cancer were downloaded. The possible signaling pathway of CETN2 was investigated by Gene set enrichment analysis (GSEA). Immune infiltration analysis was performed. Immunohistochemistry (IHC) and quantitative real-time PCR (QRT-PCR) were used to examine the expression of CETN2 in clinical samples in relation to the effectiveness of chemotherapy. The capacity of CETN2 to predict chemotherapy results was proven by receiver operating characteristic (ROC) curves after the construction of two prediction models, the logistic regression model and the decision tree model. The impact of CETN2 on prognosis was examined using the Kaplan-Meier technique. RESULTS: CETN2 was associated with NER, oxidative phosphorylation (OXPHOS) and cell cycle pathways in ovarian cancer drug-resistant samples. In clinical samples, CETN2 showed its possible correlation with immune infiltration. The protein expression level of CETN2 was significantly higher in platinum-resistant patients than that in platinum-sensitive patients, and the expression level had some predictive value for chemotherapy outcome, and high CETN2 protein expression was associated with poorer progression-free survival. CONCLUSIONS: CETN2 protein had a significant effect on ovarian cancer platinum sensitivity and prognosis, which may be related to the activation of NER, OXPHOS and cell cycle pathways upon CETN2 upregulation. Further research is necessary to determine the therapeutic application value of CETN2, which may be a new biomarker of chemoresponsiveness.

[5-Year Readmission Status and Risk Factors for Senile Dementia Patients: A Study Based on Chengdu Municipal Medical Insurance Database].

Objective: To study the status quo of the readmission of senile dementia patients in Chengdu, and to analyze the primary diagnosis, the economic burden and the influencing factors of readmission. Methods: Dementia inpatients aged 60 and above in Chengdu were the subjects of this study. The subjects were diagnosed with dementia between 2013 and 2017. Their heath insurance coverage was either the basic medical insurance for urban employees in Chengdu or the basic medical insurance for urban and rural residents of Chengdu. The rank sum test and the chi-square test were conducted to analyze the differences in readmission rate and the economic burden of hospitalization among subjects with different characteristics. Logistic regression was done to analyze the factors affecting readmission. Results: The total number of dementia inpatients over the 5-year period was 27881 patients (78820 admissions). The 30-day readmission rate was 25.14% (7011/27881) and the 5-year readmission rate was 45.79% (12767/27881). The primary diagnoses of 12767 readmitted patients mainly included dementia (28.57%), circulatory system diseases (24.26%), and respiratory system diseases (23.71%). The economic burden of hospitalization was higher for readmitted patients than that of patients who were not readmitted ( Z=33.777, P<0.001). The occurrence of readmission was correlated to the following factors, advanced age (compared to that of the 60-65 yr. group, the 70-75 yr. group: odds ratio [ OR]=1.123, 95% confidence interval [ CI]: 1.019-1.237, and the 75-80 yr. group: OR=1.123, 95% CI: 1.108-1.218), participation in the basic medical insurance for urban employees ( OR=1.674, 95% CI: 1.578-1.775), types of dementia (compared to unspecified dementia, Alzheimer's dementia group: OR=1.256, 95% CI: 1.163-1.357, Parkinson's disease dementia group: OR=1.774, 95% CI: 1.658-1.898, and mixed-type dementia group: OR=1.750, 95% CI: 1.457-2.103), disease condition (compared with patients with only dementia, those who have other diseases: OR=0.536，95% CI ：0.493-0.583), length of hospital stay ( OR=1.593, 95% CI: 1.552-1.635), and staying at a lower level hospital (compared to that of tertiary hospitals, secondary hospitals: OR=1.319, 95% CI: 1.248-1.395, primary hospitals: OR=1.744, 95% CI: 1.608-1.891, and other hospitals: OR=1.465, 95% CI: 1.311-1.537). Conclusion: Senile dementia patients have a high 30-day readmission rate, and the readmission entails heavy economic burdens on the patients. For the populations covered by medical insurance, the following features are correlated to the occurrence of readmission: advanced age, coverage by the basic medical insurance for urban employees, Alzheimer's dementia, Parkinson's disease dementia, mixed-type dementia, dementia patients without other comorbidities, extended length of stay, and hospitalization at a lower level hospital. However, further research is needed for better understanding of the specific mechanisms so that readmission of senile dementia patients can be reduced and the economic burden of the disease can be minimized.

[Cognitive Impairments and Associated Factors in Community-dwelling Elderly in Chengdu, Sichuan].

OBJECTIVE: To determine the prevalence and associated factors of cognitive impairments in the community-dwelling elderly aged 60 years or older in Chengdu of Sichuan province. METHODS: A random cluster sampling strategy was adopted to select 621 community-dwelling elderly. Face-to-face interviews were conducted to assess the cognitive status of the participants. 2 tests and logistic regression analyses were performed to identify factors associated with cognitive impairments. RESULTS: About 40.9% of the participants had cognitive impairments. Those attended primary schools had a lower risk of cognitive impairments [odds ratio OR)=0.369, P<0.001] compared with the illiterate ones. Older age OR=1.505 for 70-79 years, P=0.042; OR=3.069 for ≥80 years, P<0.001), cerebrovascular disease OR=2.159, P=0.003) and smoking OR=2.388, P<0.001) were risk factors of cognitive impairments. Men had lower risk OR=0.489, P=0.005) of cognitive impairments than women. CONCLUSION: The prevalence of cognitive impairments in community-dwelling elderly in Chengdu is high in comparison with those in other cities. Illiteracy, older age (over 70 years), women, smoking, and cerebrovascular disease are risk factors of cognitive impairments.

Pregnancy Outcomes in Women of Advanced Maternal Age: a Retrospective Cohort Study from China.

This retrospective cohort study attempts to investigate pregnancy complications and adverse pregnancy outcomes in women of advanced maternal age (AMA). Data were extracted from electronic medical records system at West China Second University Hospital of Sichuan University from January 2013 to July 2016. The study cohort consisted 8 subgroups of women on 4 different age levels (20-29 years, 30-34 years, 35-39 years and ≥40 years) and 2 different parities (primiparity and multiparity). In the study period, 38811 women gave birth at our hospital, a randomized block was used to include 2800 women of singleton pregnancy >28 gestational weeks, with 350 patients in each subgroup. Maternal complications and fetal outcomes were collected and defined according to relevant guidelines. Confounding factors representing maternal demographic characteristics were identified from previous studies and analysed in multivariate analysis. There was an increasing trend for the risks of adverse pregnancy outcomes with increasing age, especially in AMA groups. Our study showed that AMA, primiparity, maternal overweight or obesity, lower educational level and residence in rural area increased pregnancy complications and adverse fetal outcomes. Increased professional care as well as public concern is warranted.

[Prevalence of Cognitive Impairments and Its Determinants in Rural Elderly in Sichuan Province].

OBJECTIVE: To determine the prevalence of cognitive impairment and its influencing factors in rural elderly in Sichuan Province. METHODS: A multi-stage random sampling method was adopted to select participants in six towns and eighteen administrative villages in Fushun and Lizhou. The cognitive functions of 1 065 rural elderly were assessed. Factors associated with cognitive impairments of the rural elderly were identified. RESULTS: About 39. 9% of the rural elderly had cognitive impairments. Gender, age, marital status, educational attainment, regular physical activities, quality of life and social support were associated with cognitive impairments. CONCLUSION: The prevalence of cognitive impairments in rural elderly in Sichuan is high in comparison with national and international averages. Targeted interventions are needed based on the identified influencing factors.

[Catastrophic Health Expenditure before and after Compensations from the New Rural Cooperative Medical Scheme in Rural Zigong of Sichuan Province].

OBJECTIVES: To estimate catastrophic health expenditure (CHE) of rural families in Zigong, and to determine the main influencing factors of CHE. METHODS: CHE was estimated using indicators such as occurrence and average deviations. The influencing factors of CHE were identified through binary logistic regression. RESULTS: We found 6.37% catastrophic health payment headcount, 1.13% mean catastrophic payment gap, and 17.80% mean positive gap after compensations. Compensations from the new rural cooperative medical scheme (NCMS) led to a reduction of 74.81% catastrophic health payment headcount for hospitalization costs and 48.00% catastrophic health payment headcount for outpatient costs, respectively. The numbers of hospitalizations in a family, presence of patients with chronic diseases, per capita household income, and numbers of family members with a job were found to be predictors of CHE. CONCLUSIONS: Rural families that have patients with chronic diseases are vulnerable to CHE.The government should develop policies to ease the financial burdens of the families with a high accumulated health expenditure over time.

[Factors and validity analysis of Mini-Mental State Examination in Chinese elderly people].

OBJECTIVE: To examine factors that may have impact on the Mini-Mental State Examination (MMSE) screening validity, which could lead to further establishing the general model of the MMSE score in Chinese health elderly and to improve the screening accuracy of the existing MMSE reference. METHODS: Based on the data of the Chinese Longitudinal Healthy Longevity Survey (CLHLS), the MMSE scores of 19,117 normal elderly and 137 dementia patients who met the inclusion criteria were used for the analysis. The area under the curve (AUC) and validity indexes were used to compare the screening accuracy of various criteria. Multiple linear regression was used to identify factors that had impact on the MMSE score for both the normal and dementia elderly. Descriptive analysis was performed for differences in the MMSE scores by age trends and gender between the normal and dementia elderly. RESULTS: The AUC of MMSE was ≥0.75(P<0.05). The MMSE score of the normal elderly declined nonlinearly as the age grew older(male: R2=0.924, P<0.05; female: R2=0.951, P<0.05), and increased nonlinearly as the education level rose(male: R2=0.948, P<0.05; female: R2=0.859, P< 0.05). The females had significantly lower MMSE scores than the males, with a faster decline trend with age than the males (95%CI of female partial regression coefficient was not overlapped with 95%CI of male partial regression coefficient). The dementia elderly showed a much lower MMSE score (male: difference of Z score:-1.573, P<0.05; female: difference of Z score:-1.222, P<0.05) and tended to with a faster decline speed than that of the normal elderly (95%CI of dementia partial regression coefficient included 95%CI of normal partial regression coefficient). CONCLUSION: The screening validity of MMSE in CLHLS is not affected by educational level. The analysis of factors that may impact on the MMSE screening validity are gender, age, vision and residence which with validity identification. These four factors can be used as assist tool of MMSE in the screening of dementia to improve the screening accuracy.

[Reliability and validity of DSSI-23 scale in a rural elderly population].

OBJECTIVE: To determine the reliability and validity of the Duke Social Support Index (DSSI)-23 scale in a rural elderly population. METHODS: A stratified cluster random sampling strategy was adopted to select 702 rural participants aged 60 years or over in Guangyuan. Those with severe hearing disorders or mental problems were excluded. The reliability and validity of DSSI-23 scale were evaluated using internal consistency, split-half reliability,content validity, convergent validity, discriminant validity and structure validity. RESULTS: The DSSI-23 had a Cronbach's alpha efficient of 0.881 and 0.918 split-half reliability. Item-scale correlation coefficients exceed 0.35 (P<0.01), except for item three. Satisfactory (100%) convergent validity and discriminant validity were found. Confirmatory Factor Analysis (CFA) demonstrated unsatisfactory fit with the theoretical model of the scale: chi2/df = 6.884, CFI=0.807, GFI=0.850, RMSEA=0.092. CONCLUSION: DSSI-23 scale has good reliability in the elderly population, but unsatisfactory validity. Further adjustments of the scale are needed.

[Reliability and construct validity of the center for epidemiological studies depression scale in a rural women population].

OBJECTIVE: To test the reliability and construct validity of the Center for Epidemiological Studies Depression Scale (CES-D) in a rural Chinese women population. METHODS: To determine the propriety of positive questions in the CES-D, Cronbach's alpha coefficients were calculated when each of the four positive questions was deleted. Correlations between the positive affection subscale and other subscales were also tested. The four factor structure of the scale was tested using RMESA, NFI, IFI, and CFI in a confirmatory factor analysis. The internal consistency and convergent and discriminant validities of the scale were further assessed based on the four-factor structure. RESULTS: Propriety of the positive affection subscale was evident. The data fit well with the four-factor structure proposed by Radloff. The factor analysis confirmed the theoretical assumption (NFI = 0.895, IFI = 0.908, CFI = 0.908, RMSEA = 0.058). The Cronbach's alpha coefficients of the four-factor scale ranged from 0.687 to 0.735 (0.889 for the entire scale). The subscales had a correlation coefficient of 0.378-0.892 with the total score of the scale. An 85.71%-100% success rate of convergent validity experiment and 100% success rate of discriminant validity experiment was found. CONCLUSION: CES-D is a valid scale with a four-factor structure for depression screening in Chinese rural women.