The mammalian target of rapamycin (mTOR) signaling pathway plays an important role in tumorigenesis, development of tumor and tumor therapy. Previous studies have reported on the abnormalities of mTOR signaling pathway leading to the development of a variety of malignant tumors and the antitumor efficacy of various mTOR inhibitors. However, multiple studies in recent years on the mechanisms of drug resistance in tumor therapy with chemotherapy or programmed death receptor 1 inhibitors have focused on the possibility that inhibition of mTOR signaling may be associated with tumor resistance to therapy. This article summarizes the physiological functions of mTOR signaling pathway and its regulatory mechanisms in tumorigenesis, and provides a review for its mechanism of action in tumor therapy sensitivity.

Objective:To explore the causal relationship between social activity and depressive symptoms in the elderly, and to provide a reference for preventing and interventing depressive symptoms in the elderly.Methods:Data were sourced from the China Health and Retirement Longitudinal Study (CHARLS) program, involving 3 164 elderly individuals aged≥60 years with data collected in two measurements, in 2015 (T1) and 2018 (T2). The sample included 1 240 males and 1 924 females aged (71±7) years. Social activities were assessed by constructing a social activity index from the 11 social activities included in the CHARLS questionnaire and the frequency of their activities. The depressive symptoms were assessed using the short version of the Center for Epidemiological Studies Depression Scale (the 10-item Center for Epidemiological Studies Depression Scale, CESD-10). A mixed-design ANOVA was used to explore the trends in social activity and depressive symptoms over time and across genders in the elderly adults. Pearson correlation analysis was used to investigate whether social activity and depressive symptoms in the elderly met the criteria for simultaneous and sequential correlations, followed by a cross-lagged model to analyze the causal temporal or mutual prediction between social activeness and depressive symptoms over a 3-year intervals.Results:The social activity of elderly men at T2 was significantly lower than at T1 ( F=21.00, P<0.001), while no significant difference observed in elderly women ( F=0.31, P<0.001). At both T1 and T2, elderly men scored higher in social activity than elderly women [T1: 2.93±2.98 vs 2.55±2.65,T2: 2.28±2.49 vs 2.24±2.43); F=43.60, 11.24, both P<0.01]. Depressive symptoms at T2 were higher than at T1 for both elderly men and elderly women ((male: 1.90±6.10 vs 21.52±6.08, female: 23.84±6.54 vs 23.07±6.44); F=5.20, 32.77, both P<0.05). Elderly men scored lower than elderly women on depression symptoms at both T1 and T2 (T1: F=45.74, P<0.001; T2: F=69.96, P<0.001). Pearson correlation analysis showed a negative correlation between social activity and depressive symptoms at both measurement points (T1: r=-0.329, P<0.01; T2: r=-0.343, P<0.01), and a positive correlation across T1 and T2 ( r=0.391, 0.573; both P<0.01), meeting the criteria for simultaneous and sequential correlations, and supporting the basic assumptions of cross-lagged design. Cross-lagged analysis revealed that T1 social activity negatively predicted T2 depressive symptoms (β=-0.128, P<0.001), and T1 depressive symptoms negatively predicted T2 social activity (β=-0.202, P<0.001). Conclusion:There is a bidirectional predictive relationship between social activity and depression symptoms in the elderly. Depression symptoms lead to a decrease in social activity, and a decrease in social activity predicts an exacerbation of depression in the elderly.

Objective:To explore the causal relationship between social activity and depressive symptoms in the elderly, and to provide a reference for preventing and interventing depressive symptoms in the elderly.Methods:Data were sourced from the China Health and Retirement Longitudinal Study (CHARLS) program, involving 3 164 elderly individuals aged≥60 years with data collected in two measurements, in 2015 (T1) and 2018 (T2). The sample included 1 240 males and 1 924 females aged (71±7) years. Social activities were assessed by constructing a social activity index from the 11 social activities included in the CHARLS questionnaire and the frequency of their activities. The depressive symptoms were assessed using the short version of the Center for Epidemiological Studies Depression Scale (the 10-item Center for Epidemiological Studies Depression Scale, CESD-10). A mixed-design ANOVA was used to explore the trends in social activity and depressive symptoms over time and across genders in the elderly adults. Pearson correlation analysis was used to investigate whether social activity and depressive symptoms in the elderly met the criteria for simultaneous and sequential correlations, followed by a cross-lagged model to analyze the causal temporal or mutual prediction between social activeness and depressive symptoms over a 3-year intervals.Results:The social activity of elderly men at T2 was significantly lower than at T1 ( F=21.00, P<0.001), while no significant difference observed in elderly women ( F=0.31, P<0.001). At both T1 and T2, elderly men scored higher in social activity than elderly women [T1: 2.93±2.98 vs 2.55±2.65,T2: 2.28±2.49 vs 2.24±2.43); F=43.60, 11.24, both P<0.01]. Depressive symptoms at T2 were higher than at T1 for both elderly men and elderly women ((male: 1.90±6.10 vs 21.52±6.08, female: 23.84±6.54 vs 23.07±6.44); F=5.20, 32.77, both P<0.05). Elderly men scored lower than elderly women on depression symptoms at both T1 and T2 (T1: F=45.74, P<0.001; T2: F=69.96, P<0.001). Pearson correlation analysis showed a negative correlation between social activity and depressive symptoms at both measurement points (T1: r=-0.329, P<0.01; T2: r=-0.343, P<0.01), and a positive correlation across T1 and T2 ( r=0.391, 0.573; both P<0.01), meeting the criteria for simultaneous and sequential correlations, and supporting the basic assumptions of cross-lagged design. Cross-lagged analysis revealed that T1 social activity negatively predicted T2 depressive symptoms (β=-0.128, P<0.001), and T1 depressive symptoms negatively predicted T2 social activity (β=-0.202, P<0.001). Conclusion:There is a bidirectional predictive relationship between social activity and depression symptoms in the elderly. Depression symptoms lead to a decrease in social activity, and a decrease in social activity predicts an exacerbation of depression in the elderly.

Objective:To explore the blood pressure levels and the influencing factors of hypertension among Hainan centenarians, and provide basic data for the further blood pressure related studies of the centenarian population.Methods:The baseline data were from China Hainan Centenarian Cohort Study (CHCCS). This cross-sectional data, based on the community population, was a complete sample study of centenarians, including questionnaire survey, physical examination and physiological index detection. A total of 1 002 centenarians were recruited to describe the blood pressure level. According to the guidelines for the prevention and treatment of hypertension in Chinese adults in 2018, the prevalence of hypertension was analyzed.Results:The median levels of systolic blood pressure, diastolic pressure and pulse pressure were 152.0, 76.0 and 76.5 mmHg, respectively. Blood pressure level was higher in females than in males. The prevalence of hypertension was 71.9%, mainly in isolated systolic hypertension with the prevalence of 60.1%. The results of multivariate analysis showed that the risk of hypertension in women was higher than that in men ( OR=1.624, 95% CI: 1.155-2.283), and the risk of hypertension in the northern ( OR=0.625, 95% CI: 0.434-0.901) and central areas ( OR=0.586, 95% CI: 0.346-0.993) was lower than that of the Eastern. Conclusion:The prevalence of hypertension, mainly in isolated systolic hypertension, showing gender and regional distribution differences.

Objective: To learn the sequence characteristics of C2-V4 of HIV-1 env genes and the epitope variation of representative broadly monoclonal neutralizing antibody in Fuxin, so as to provide evidence for the HIV-1 variation trend and the biological characteristics of V3 loop. Methods : The whole blood samples of 112 HIV-1 cases in Fuxin Health Service Center from 2018 to 2019 were collected and the DNA was extracted. The C2-V4 of env genes were amplified by nested-PCR and the PCR products were subjected to sequencing. The bioinformatics analysis was carried out using MEGA software, and the V3-tip motifs, co-receptors, net charge and characteristic amino acids were analyzed using HIV Database. Results: Totally 101 effective gene sequences were obtained, and 5 types of V3-tip motifs were found. Among them, 77 pieces of GPGQ ( 76.24% ) were found in CRF01_AE, CRF07_BC, CRF65_cpx and G subtypes; 19 pieces of GPGR ( 18.81% ) were found in CRF01_AE, CRF07_BC and B subtypes; 3 pieces of GPGH, 1 piece of GPGK and 1 piece of GPGA were only found in CRF01_ AE subtype. The co-receptor was mainly CCR5 ( 84, 83.17% ) . The net charge numbers of V3 loops in CRF01_ AE, CRF07_ BC, B, CRF65_cpx and G were 3.28±1.17, 3.22±0.92, 4.25±0.83, 2.50±0.50 and 3, respectively. The mutation rates of neutralizing antibodies binding b12 and VRC01 were 0-9.90%. The deletion rates of N-glycosylation sites of 295 and 332 were 18.81% and 14.85%, without the loss of both sites. Conclusions The HIV-1 strains in Fuxin from 2018 to 2019 are macrophage-tropic and non-syncytium-inducing, with GPGQ as the main type of V3-tip motif, CCR5 as the main co-receptor, slow replication and low ability to escape neutralizing antibodies.

Objective:To investigate the prevalence of depression and to analyze its determinants among centenarians in Hainan.Methods:A cross-sectional study on centenarians was conducted in Hainan from June 2014 to December 2016.A total of 910 centenarians, including 166 males and 744 females, were interviewed in their domiciles by trained investigators.A 15-item Geriatric Depression Scale(GDS-15)was used to assess depression for centenarians, and general sociodemographic details, sleep quality, cognitive function, activities of daily living, and lifestyles were recorded.Multivariate logistic regression analysis was used to determine major related factors for depression in centenarians.Results:Of the 910 centenarians, 292 were regarded as depressed and the prevalence was 32.1%.Univariate analysis showed that there were significant differences in gender, education, marital status, self-reported health, incontinence, dietary habits, sleep quality, activities of daily living, cognitive function, outdoor activities, watching TV, and social engagement between subjects with and without depression( P<0.05). Multivariate logistic regression analysis showed that living conditions, self-reported health, activities of daily living, and sleep quality were independent related factors for depression in centenarians( P<0.05). Among the above related factors, living with families( OR=0.50, P=0.026)and good sleep quality( OR=0.67, P=0.010)were protective factors for depression, whereas poor self-reported health( OR=3.34, P<0.001)and disability( OR=2.37, P=0.002)were risk factors for depression in centenarians. Conclusions:Living conditions, self-reported health, activities of daily living, and sleep quality were independently correlated with depression in Hainan centenarians.This study provides empirical evidence for depression interventions and mental health improvement in centenarians.

Objective: To evaluate the health status of Hainan centenarians and compare the gender disparity, and to determine whether the'male-female health-survival paradox’is present among them. Methods: A cross-sectional study was conducted on the health status and gender disparity of individuals aged 100 and over in Hainan province from June 2014 to December 2016.Data of sociodemographics, lifestyles as well as health-related parameters were collected.The multi-dimensional health assessment of centenarians was conducted based on the recognition of standard on Chinese healthy elderly in 2013. Results: A total of 940 centenarians(men 18.6%, women 81.4%)were included.The prevalences of hypertension, diabetes and dyslipidemia were 66.1%, 9.8%, and 21.2%, respectively, while no significant gender difference was found.Male centenarians were more independent in activity of daily living than did female centenarians(41.1% vs.25.9%, P<0.001). The prevalences of dementia(7.7% vs.4.0%)and depression(33.6% vs.18.9%)were more dominant in females than in males.Multivariate logistic regression showed that the proportions of functional disability, depression and sleep disorders were higher in female centenarians than in male centenarians(P<0.05)after adjusting for general demographic characteristics, lifestyle and other health indicators. Conclusions Although the female proportion dominates the centenarian population, female general health states are worse than male centenarians.More attentions on physical and mental health should be paid to the female centenarians.

Objective: To study the correlation of lifestyle characteristics with thyroid nodules in a population-based sample of centenarians in Hainan. Methods: The study was based on China Hainan Centenarian Cohort Study (CHCCS) conducted in 18 cities and counties in Hainan province from 2014 to 2016. A group of multidisciplinary team interviewed and examined local centenarians with structured questionnaires and ultrasonography procedures. A total of 918 centenarians were analyzed after excluding those who refused ultrasonographic examinations or had relevant missing data. Thyroids of centenarians were examined by 3-year experienced sonographer, details on lifestyle characteristics and dietary habits were collected by standard procedure. Results: Of the 918 centenarians, 683 (74.4%) had thyroid nodules under the ultrasonography procedures. The prevalence of thyroid nodules in different group of areca nut consumption varied significantly (P<0.05). In multivariate logistic regression model, the results showed female and areca nut intake were independently associated with thyroid nodules in centenarians (P<0.05). Conclusions The modifiable variables including areca nut intake as well as non-modifiable such as gender are independent determinants of thyroid nodules in centenarians. Further studies are warranted to explore and verify these associations in populations with different ranges of age.

Objective To investigate the health status,functional ability,mental psychology,health care and other longevity-related characteristics of individuals aged ≥ 100 years as well as risk factors in Hainan province,China.Methods China Hainan Centenarian Cohort Study (CHCCS) is a community-based,prospective cohort study to establish multi-dimensional database consisting of questionnaire findings,anthropometric parameters and biological specimens as well as imaging features.With the household registration information provided by the Department of Civil Affairs of Hainan province,a baseline survey was conducted in centenarians in 18 counties in Hainan with the oldest old in 5 counties as controls between 2014 and 2017.The survey included face to face interview,physical examination and biological specimen collection.After the baseline survey,the participants of CHCCS were followed up at an interval of 2 years to collect the information about their living status,disease status or major death causes.Results According to the information provided by the Department of Civil Affairs of Hainan province in 2014,the survey found that 1 473 centenarians were still living.By December 2016,1 002 of them had agreed to be surveyed.The average age of 722 centenarians with complete information in the baseline survey was (102.7± 2.7) years,the majority of them were females (83.0％),widows (88.8％),in Han ethnic group (84.5％),lived with family members (87.8％),illiterates (89.7％) and farmers (81.0％).Conclusion CHCCS has provided longevity-related information of the large longevity population and collected the valuable and rare biological specimens with great urgency to establish an interdisciplinary platform and base for longevity,senility and healthy aging research.

Objective To investigate the Activity of Daily life (ADL) among individuals aged 100 and above,in Hainan.Methods From June 2014 to December 2016,a community-based cross-sectional study was conducted among individuals aged 100 and over in Hainan province.Data regarding basic information,ADL,prevalence of major age-related diseases was collected in this population.Loss of ADL among these centenarians was described and its determinants examined.Results The prevalence of ADL loss in centenarian population was 72.5％,with the top four items of ADL loss as stair-climbing (79.0％),moving (59.1％),walking (44.3％) and using toilet (41.3％).Results showed that tea consumption,good both on vision and audition were possible protective factors for the functions of ADL.Low level of education and vitamin D deficiency seemed as risk factors for the slowing-down of ADL (P＜0.05).Conclusions The prevalence of ADL loss among centenarians appeared relatively high.Years of education,tea consumption,degrees of vision,audition and vitamin D deficiency were possible risk factors responsible for the ADL loss in this centenarian population.