Palliative care is a way to help end-of-life populations improve their quality of life， and its development in practice cannot be separated from the level of education in palliative care. At present， some medical schools in palliative care education compared with western developed countries have problems such as imperfect construction of hospice curriculum system， lack of medical students’ hospice knowledge； insufficient interdisciplinary teaching faculty， weak palliative care awareness of medical students； single teaching evaluation mode； weak palliative care practice teaching links. To this end， it is necessary to improve the palliative care curriculum system， explore rich and diverse teaching methods； strengthen interdisciplinary teaching and faculty development， enhancing the awareness of palliative care among medical students；establish a scientific and effective evaluation method， carry out multi-dimensional dynamic assessment； expand the palliative care practice teaching base， and accurately improve the practical skills of medical students in palliative care， and other countermeasures to improve the level of palliative care education， and to help the strategy of Healthy China.

The influenza A virus (IAV), renowned for its high contagiousness and potential to catalyze global pandemics, poses significant challenges due to the emergence of drug-resistant strains. Given the critical role of RNA polymerase in IAV replication, it stands out as a promising target for anti-IAV therapies. In this study, we identified a novel C-3-substituted oleanolic acid benzyl amide derivative, A5, as a potent inhibitor of the PA_C-PB1_N polymerase subunit interaction, with an IC₅₀ value of 0.96 ± 0.21 μmol/L. A5 specifically targets the highly conserved PA_C domain and demonstrates remarkable efficacy against both laboratory-adapted and clinically isolated IAV strains, including multidrug-resistant strains, with EC₅₀ values ranging from 0.60 to 1.83 μmol/L. Notably, when combined with oseltamivir, A5 exhibits synergistic effects both in vitro and in vivo. In a murine model, dose-dependent administration of A5 leads to a significant reduction in IAV titers, resulting in a high survival rate among treated mice. Additionally, A5 treatment inhibits virus-induced Toll-like receptor 4 activation, attenuates cytokine responses, and protects against IAV-induced inflammatory responses in macrophages. In summary, A5 emerges as a novel inhibitor with high efficiency and broad-spectrum anti-influenza activity.

Background::Programmed death 1 (PD-1) blockade plus chemotherapy has become the new first-line standard of care for patients with advanced non-small-cell lung cancer (NSCLC). Yet not all NSCLC patients benefit from this regimen. This study aimed to investigate the predictors of PD-1 blockade plus chemotherapy in untreated advanced NSCLC.Methods::We integrated clinical, genomic, and survival data from 287 patients with untreated advanced NSCLC who were enrolled in one of five registered phase 3 trials and received PD-1 blockade plus chemotherapy or chemotherapy alone. We randomly assigned these patients into a discovery cohort ( n = 125), a validation cohort ( n = 82), and a control cohort ( n = 80). The candidate genes that could predict the response to PD-1 blockade plus chemotherapy were identified using data from the discovery cohort and their predictive values were then evaluated in the three cohorts. Immune deconvolution was conducted using transcriptome data of 1014 NSCLC patients from The Cancer Genome Atlas dataset. Results::A genomic variation signature, in which one or more of the 15 candidate genes were altered, was correlated with significantly inferior response rates and survival outcomes in patients treated with first-line PD-1 blockade plus chemotherapy in both discovery and validation cohorts. Its predictive value held in multivariate analyses when adjusted for baseline parameters, programmed cell death ligand 1 (PD-L1) expression level, and tumor mutation burden. Moreover, applying both the 15-gene panel and PD-L1 expression level produced better performance than either alone in predicting benefit from this treatment combination. Immune landscape analyses revealed that tumors with one or more variation in the 15-gene panel were associated with few immune infiltrates, indicating an immune-desert tumor microenvironment.Conclusion::These findings indicate that a 15-gene panel can serve as a negative prediction biomarker for first-line PD-1 blockade plus chemotherapy in patients with advanced NSCLC.

Objective:To investigate the distribution characteristics of cognition-related lifestyles of elderly in communities and explore the integrated effects on early cognitive decline.Methods:The participants were from the Project of Prevention and Intervention of Neurodegenerative Disease for Elderly in China. A total of 2 537 older adults aged ≥60 years without dementia in the 2015 baseline survey and the 2017 follow-up survey were included. The information about their cognition-related lifestyles, including physical exercise, social interaction, leisure activity, sleep quality, smoking status, and alcohol consumption, were collected through questionnaire survey and the integrated scores were calculated. Multivariate logistic regression analysis was used to assess the association between integrated cognition-related lifestyle score and early cognitive decline.Results:In the 2 537 older adults surveyed, 28.7% had score of 5-6, while only 4.8% had high scores for all 6 healthy lifestyles. Significant differences in healthy lifestyle factor distributions were observed between men and women. Multivariate logistic regression model showed that the risks for early cognitive decline in the older adults who had lifestyle score of 4 and 5-6 were lower than that in those with lifestyle score of 0-3 ( OR=0.683, 95% CI: 0.457-1.019; OR=0.623, 95% CI: 0.398-0.976; trend P=0.030). In the women, the risks for early cognitive decline was lower in groups with score of 4 and 5-6 than in group with score of 0-3 ( OR=0.491, 95% CI: 0.297-0.812; OR=0.556, 95% CI: 0.332-0.929; trend P=0.024). Conclusion:Cognition-related healthy lifestyles are associated with significantly lower risk for early cognitive decline in the elderly, especially in women.

Centenarians are known as the "model population" in the study of healthy aging. Understanding their characteristics of health and longevity and its related influencing factors would facilitate the exploration of the possible path to achieve health and longevity under the background of population aging in China. In recent years, the population based observational studies, including China Hainan Centenarian Cohort Study (CHCCS), have found the main health characteristics of centenarians and their relationship with quality of life. This paper summarizes the relevant research results from CHCCS in recent years, and compare them with the results of similar domestic studies. The main health indicators include blood pressure, blood lipid, blood glucose, hemoglobin, body measurement and renal function. The health outcomes including diet, nutrition, health-related quality of life, activities of daily living, geriatric syndrome. The results are expected to provide epidemiological evidence for the development of healthy aging policies.

Objective:To explore the association between parathyroid hormone (PTH) and all-cause death in the centenarians in Hainan Province.Methods:The study was based on China Hainan Centenarian Cohort Study, a total of 1 002 centenarians were included in the baseline survey, the follow up was conducted to collect the information about their death outcome. The association between baseline PTH level and all-cause death was analyzed by Cox proportional risk regression model using continuous variables, dichotomous variables, and quad variables as independent variables of the centenarians.Results:As of May 31 st, 2021, a total of 522 centenarians had died in the follow up period, the median of the follow up time was 4.16 (1.31,5.04) years, and the mortality rate was 52.10%. After fully adjusting the covariates, the multiple Cox proportional hazards regression analyses showed that the risk of all-cause death increased by 3.7% for every 10 pg/ml increase in PTH value, the HR was 1.037 (95% CI: 1.007-1.067) in all the centenarians. The risk of death in the centenarians in the highest PTH group was 1.458 (95% CI: 1.131-1.878) times higher than that in the lowest PTH group. Conclusions:Higher parathyroid hormone level was associated with the elevated risk for all-cause death in the centenarians in Hainan. PTH can be used as a reference index for the prediction of the death risk of long-lived elderly in community.

Objective:To examine the association between depression and all-cause death in centenarians in Hainan Province.Methods:Based on China Hainan Centenarian Cohort Study, 1 002 centenarians with integral data were included in the baseline survey, follow up was conducted to collect the information about their survival status and death outcome. Depression was evaluated by the 15-item Geriatric Depression Scale (GDS-15) and based on the evaluation scores, the mental status of the centenarians was classified as: severe depressive disorder (MDD; score ≥10), minor depressive disorder (MnDD; score 6-9), and normal status (score ≤5). Multivariable-adjusted Cox proportional hazards regression models was used to estimate the hazard ratios ( HRs) and 95% CIs. Results:As of May 31 st, 2021, a total of 522 deaths had been reported, with a mortality density of 152.39/1 000 person-years and a median follow up time M( Q1, Q3) of 4.16 (1.31, 5.04) years, in the centenarians. After adjusting the factors of socio-demographic characteristics and lifestyle, multivariate Cox regression analysis showed that the risk of all-cause mortality increased by 3.1% for every 1-point increase in GDS-15 score ( HR=1.031, 95% CI: 1.002-1.061). Compared with centenarians with normal status, the risk of mortality in the centenarians with MDD increased by 35.9% ( HR=1.359, 95% CI: 1.023-1.806), the centenarians with MDD had an average 1.94 years of life lost. Among the female centenarians, the risk of mortality in MnDD group and MDD group increased by 29.3% ( HR=1.293, 95% CI: 1.053-1.590) and 42.3% ( HR=1.423, 95% CI: 1.047-1.935) compared with normal group, those with MDD had an average 1.71 years of life lost. Conclusions:Depression was related to the increased risk of all-cause death and life lost in the centenarians in Hainan.

Objective:To describe and analyze the relationship between traditional and new obesity related anthropometric indicators and all-cause death in centenarians in Hainan, the traditional and new obesity related anthropometric indicators included BMI, waist circumference (WC), waist hip ratio (WHR), waist height ratio, calf circumference (CC), waist-calf ratio (WCR), lipid accumulation product (LAP), visceral adiposity index (VAI), Chinese visceral adiposity index (CVAI), a body shape index (ABSI), a body shape index of Chinese (CABSI) and body roundness index.Methods:A total of 1 002 centenarians in Hainan were selected by cluster sampling. The M( Q1,Q3) follow-up time was 4.16 (1.31, 5.04) years and the outcome was all-cause death. Multiple Cox regression model was used to analyze the relationship between the obesity related anthropometric indicators and all-cause death, and the area under receiver operating characteristic curve was used for comparison. Results:In all the centenarians, CC had the strongest power to predict death, with area under curve (AUC) of 0.61 (95% CI:0.57-0.64), the gender specific results were consistent with that in overall population ( P<0.05), followed by WCR with AUC of 0.58, and then BMI, LAP and WC with AUC of 0.55, 0.55 and 0.54 respectively, while CABSI, WHR and VAI had the weaker power to predict death with AUC of 0.51, 0.50 and 0.50 respectively. Conclusions:This was the first study to prospectively compare and analyze the association between 12 obesity related anthropometric indicators and all-cause death in a large sample cohort of centenarians in China. It was found that CC had the best prediction power for death, and the risk for death decreased with the increase of CC value in a dose-response manner. It is suggested that CC can be used as a reference index for death risk monitoring in the elderly.

Objective:To understand the associations of various levels of systolic and diastolic blood pressure levels and related factors with all-cause death in the centenarians in Hainan Province.Methods:The data were obtained from China Hainan Centenarian Cohort Study, a prospective cohort study which included 1 002 centenarians. Cox proportional risk regression models were used to analyze the associations of blood pressure and related factors with all-cause death in the centenarians.Results:As of May 31, 2021, with the median of the follow-up time of 4.16 years, and the mortality density had reach 15.24 per 100 person-years. After grouping by SBP and DBP quartiles, the Q1 of SBP and Q2 of DBP caused the lowest mortality density (12.73 per 100 person-years and 14.10 per 100 person-years relatively). In all the centenarians, compared with the Q1 of SBP (≤137 mmHg, 1 mmHg=0.133 kPa), Q2, Q3 and Q4 were all positively associated with all-cause death. In the female population, the HRs of SBP's Q2, Q3 and Q4 were 1.343, 1.355 and 1.420 respectively ( Q1 as reference), and the HRs of DBP's Q1, Q3 and Q4 were 1.468, 1.800 and 1.504 respectively ( Q2 as reference), showing a roughly U-shaped association. Interactive analysis showed multiplicative interaction between SBP and BMI. Conclusions:In the centenarians in Hainan, different levels of systolic and diastolic blood pressure were associated with all-cause death. In the centenarians, DBP might have a suitable level or range in which the risk of death is relatively low. Different BMI status might affect the associations of blood pressure levels with death outcomes.

Objective:To investigate the distribution characteristics of sex hormones and their relationship with all-cause mortality in Hainan female centenarians.Methods:All the subjects were from China Hainan Centenarian Cohort Study. A total of 717 female centenarians were included in the final analysis. Kaplan-Meier method was used to draw the survival curve, and Cox proportional hazard regression was used to analyze the relationship between sex hormones and survival time.Results:The M( Q1, Q3) of estradiol and progesterone among female centenarians was 32.60 (18.40, 58.70) pmol/L and 0.62 (0.32, 1.01) nmol/L. The estradiol (pmol/L) and progesterone (nmol/L) in the survival and death groups were 26.65 vs.37.80, 0.54 vs.0.69, respectively, with statistical differences ( P<0.05). Cox multivariate analysis showed that estradiol and progesterone were significantly associated with death ( P<0.05), the hazard ratio ( HR) of estradiol Q4 was 1.58 (95% CI: 1.17-2.15), and the HR of progesterone Q3 was 1.53 (95% CI: 1.10-2.12), HR for Q4 was 1.63 (95% CI: 1.15-2.32). Subgroup and cross-analysis showed that estradiol was statistically significant with hypertension, diabetes, and low high-density lipoprotein cholesterol ( P<0.05), and progesterone interacted with diabetes ( P=0.016), while testosterone interacted with low high-density lipoprotein cholesterol ( P=0.034). Conclusion:It is suggested that the estrogen levels of female centenarians in Hainan were associated with a higher mortality risk and an increased risk of cardiovascular metabolic disease (such as diabetes, hypertension, and abnormal lipid metabolism).