ABSTRACT
Background: Cognitive decline is a growing public health concern. However, presently, only a few large-scale studies are available on the prevalence of cognitive decline worldwide, and the relationship between nutrition and cognitive decline remains unclear and requires further investigation, especially among Chinese centenarians and oldest-old adults. This study aimed to assess the prevalence of cognitive decline among Chinese centenarians and oldest-old adults, its associated factors, and explore a possible connection with nutrition, to provide new directions for the prevention of cognitive decline in Chinese centenarians and oldest-old adults. Methods: Based on the China Hainan Centenarian Cohort Study (CHCCS), a household survey was conducted among all the centenarians and oldest-old adults residing in 16 cities and counties of Hainan province from June 2014 to June 2016. This study included 946 centenarians and oldest-old adults (412 and 534, respectively). Cognitive function was measured using the mini-mental state examination (MMSE). Findings: The total prevalence of cognitive decline was 76·6% (725 participants). Centenarians had a significantly higher prevalence of cognitive decline compared to oldest-old adults [359 centenarians (87·1%) vs. 366 oldest-old adults (68·5%)]. Centenarians and oldest-old adults with cognitive decline had significantly lower prognostic nutritional index (PNI) and mini nutrition assessment-short form (MNA-SF) than those without cognitive decline (P < 0·05). Multivariate logistic regression analyses showed that participants with higher PNI and MNA-SF were less likely to have cognitive decline. Multivariate linear regression analyses showed that PNI and MNA-SF were positively associated with MMSE (P < 0·05). Interpretation: Malnutrition was positively associated with cognitive decline among Chinese centenarians and oldest-old adults. It is therefore important for clinicians and community health workers to pay attention to malnutrition in these populations and provide supplemental nutrients to prevent cognitive decline. Funding: This work was supported by grants from the National Natural Science Foundation of China (81900357, 81903392, 81941021, 81901252, 82001476, 81802804, 81801251), the Military Medical Science and Technology Youth Incubation Program (20QNPY110, 19QNP060), the Excellent Youth Incubation Program of Chinese People's Liberation Army General Hospital (2020-YQPY-007), the Military Medicine Youth Program of Chinese People's Liberation Army General Hospital (QNF19069, QNF19068), the National Key R&D Program of China (2018YFC2000400), the National S&D Resource Sharing Service Platform Project of China (YCZYPT[2018]07), the Innovation Platform for Academinicians of Hainan Province, the Hainan Major Scientific and Technological Cooperation Project (2016KJHZ0039), the China Postdoctoral Science Foundation funded project (2019M650359, 2020M682816, 2021T140298), the Medical Big Data R&D Project of Chinese People's Liberation Army General Hospital (MBD2018030), the National Geriatric Disease Clinical Medicine Research centre Project (NCRCG-PLAGH-2017-014), the Central Health Care Scientific Research Project (W2017BJ12), the Hainan Medical and Health Research Project (16A200057), the Sanya Medical and Health Science and Technology Innovation Project (2016YW21, 2017YW22, 2018YW11), and the Clinical Scientific Research Supporting Fund of Chinese People's Liberation Army General Hospital (2017FC-CXYY-3009).
ABSTRACT
In this study, the relationship between CpG island methylation and smoking and DNA methyltransferase in the occurrence and development of lung adenocarcinoma was explored by detecting p16 promoter methylation status. Protein and mRNA levels of p16 were detected by immunohistochemistry and in situ hybridization assays. p16 gene promoter and exon 1 CpG island locus Hap II sites methylation status was analyzed with the methylation-specific PCR. Only 4 of 40 p16-positive cases were detected to methylate on CpG islands with 10% methylating rate whereas 18 of p16-negative cases were methylated up to 36.73% of methylating rate. The methylating rates of both p16-positive and p16-negative groups were significantly different. 17 of 50 cases with smoking from total 89 lung adenocarcinoma cases were detected to methylate on CpG islands while only 5 of the remaining 39 non-smokers to methylate. The difference of the methylating rates in both smokers and non-smokers was significant to suggest the closely association of CpG island methylation of p16 with smoking. Furthermore, p16 promoter CpG islands were detected to methylate in 15 of 35 cases with higher DNA methyltransferase activity whereas only 7 detected to methylate in the remaining 54 cases with lower DNA methyltransferase activity. p16 promoter CpG island methylation likely made p16 expressing silence thus contributed to the tumorigenesis of lung adenocarcinoma. Smoking is likely to promote p16 CpG island methylation or by its effect of the activity and metabolism of DNA methyltransferase 1 (DNMT) on CpG island methylation status.
ABSTRACT
The aim of this study was to explore the association of CpG islands methylation of liver kinase B1 (LKB1) with primary lung cancer and smoking, providing a theoretical basis for the demethylating drug to treat lung cancer by detecting the LKB1 promoter CpG methylation. mRNA expression of LKB1 were detected by in situ hybridization and methylation status on Hap II locus of the promoter of LKB1 was analyzed by methylation-specific polymerase chain reaction (PCR). 7 of 80 LKB1 positive cases had methylation on CpG islands while 18 of 44 LKB1 negative cases had methylation on CpG islands. The difference was significant between CpG island methylation and LKB1 expression. 8 of 54 cases of early and middle lung cancer were detected LKB1 promoter CpG island methylation while 30 controls were not detected, the difference was significant. 5 of 64 more-than-5-year cases had methylation on CpG islands while 20 of 60 less-than-5-year cases had methylation. The difference was significant between of 5-year survival and CpG island methylation of LKB1. 22 of 74 smoking cases of lung cancer had methylation on CpG islands of LKB1 while only 3 of 50 non-smoking cases had methylation. The difference of smoking and CpG island methylation of LKB1 was significant. LKB1 promoter CpG islands aberrant methylation is closely associated with the occurrence, development and prognosis of lung cancer, especially with smoking history including clinical early diagnosis and prognosis. CpG islands methylation in the promoter of LKB1 is likely important one of the mechanism of smoking-associated lung cancer.
ABSTRACT
OBJECTIVE: To investigate the values of factors based on PIRO conception in predicting the prognosis of critical patients. METHODS: The clinical data of critical patients admitted to Hainan Branch of PLA General Hospital from December 2011 to August 2013 were retrospectively analyzed. The patients were randomly divided into non-survivors and survivors groups according to 28-day outcome. Predisposition (P), injury (I), response (R) and organ dysfunction induced by injury (O) were compared between two groups. The indexes with statistical significance (P<0.2) by univariate analysis were included in multivariate logistic regression analysis, and the receiver operating characteristic curve (ROC curve) was plotted to evaluate the values of factors based on PIRO conception in predicting the prognosis of critical patients. RESULTS: One hundred and eighty-seven critical patients were enrolled, and among them 75 (40.1%) patients died. Univariate analysis showed that the age, underlying disease scores, history of cardiovascular disease, diabetes mellitus, and cerebrovascular disease, positive blood culture, whether or not complicated with acute respiratory distress syndrome (ARDS) or severe sepsis/septic shock, procalcitonin (PCT), acute physiology and chronic health evaluation II (APACHE II), acute pathophysiology score (APS) and sequential organ failure assessment (SOFA) were found to be the factors related with the prognosis (all P<0.2). Multivariate logistic regression analysis showed that the underlying disease scores [odds ratio (OR)=1.874, 95% confidence interval (95%CI) 1.138-3.084, P=0.014], whether patients occurrence of severe sepsis/septic shock (OR=0.167, 95%CI 0.064-0.435, P=0.000) and SOFA scores (OR=1.498, 95%CI 1.283-1.750, P=0.000) were independent factors for predicting 28-day mortality. The new model combined with above factors had more prognostic value in predicting the mortality than a single variable. The area under ROC curve (AUC) for PIRO model based on indexes with statistical significance by univariate analysis was 0.877 (0.821-0.934), P=0.000. AUC for PIRO model based on underlying disease scores, severe sepsis/septic shock, SOFA scores was 0.871 (0.814-0.928), P=0.000. AUC for SOFA was 0.762 (0.687-0.837), P=0.000. AUC for APS was 0.726 (0.647-0.805), P=0.000. AUC for underlying disease scores was 0.678 (0.593-0.763), P=0.000. AUC for PCT was 0.636 (0.548-0.724), P=0.004. AUC for age was 0.618 (0.532-0.705), P=0.013]. CONCLUSIONS: The multivariate regression analysis based on PIRO system may help to predict 28 days mortality in critical patients.
