OBJECTIVE To provide a reference for the definition of the legal attributes of the provincial Chinese herbal pieces processing norms and the improvement of legal expression for the drug standards in Drug Administration Law. METHODS Based on the legal evolution of local drug standards in China， the composition of national drug standards for Chinese herbal pieces and the composition of current provincial Chinese herbal pieces processing norms were analyzed； at the same time， based on the method of legal interpretation， the legal connotation of the provincial Chinese herbal medicine processing norms in Drug Administration Law was investigated. RESULTS & CONCLUSIONS In the practice of drug supervision， the provincial Chinese herbal pieces processing norms are essentially local drug standards. The newly revised Drug Administration Law defines the drug standards specifically， but does not stipulate the legal attribute of drug standards for the provincial Chinese herbal pieces processing norms， and there are certain legislative technical defects. It is suggested that when amending the Drug Administration Law， the legal attributes of the drug standards of the provincial Chinese herbal medicine processing norms should be clarified.

Objective To explore the network structure of anxiety,depression and sleep among individuals under long-term high-altitude exposure.Methods A total of 303 subjects who had resided at high altitudes for more than 6 months on end were selected.The insomnia severity index(ISI),patient health questionnaire(PHQ-9),and generalized anxiety disorder scale(GAD-7)were employed to assess insomnia,depression and anxiety before network analysis was conducted to identify the central and bridge nodes in the symptom network.Results The incidence of moderate or severe depression,anxiety and insomnia were 38.9％[95％confidence interval(CI):33.4％-44.5％],23.1％(95％CI:18.3％-27.9％),and 18.5％(95％CI:14.1％-22.9％),respectively."Noticeability of sleep problems by others"had the highest expected influence centrality,followed by"sleep maintenance""uncontrollable worry""restlessness"and"sleep problems".Five bridge symptoms were identified:"sad mood""sleep problems""restlessness""feeling afraid"and"trouble relaxing".Conclusion Sleep-related symptoms play a crucial role in the overall network structure,serving as both central and bridge nodes.Additionally,the"feeling down or depressed"acts as a bridge node and holds importance in the comorbidity network of anxiety and depression.Targeting these key symptoms through intervention and prevention strategies may improve the psychological well-being of individuals with long-term residence in high-altitude regions.

Cognitive dysfunction,predominantly a consequence of neurodegenerative disorders,is a burgeoning health issue.Odor molecules have the unique ability to circumvent the blood-brain barrier through the olfactory pathway,exerting a direct influence on cognitive-related brain regions including the entorhinal cortex,hippocampus,and amygdala,without transiting through the thalamus.These olfactory molecules,mostly sourced from natural plant essential oils,are character-ized by significant volatility,minimal adverse reactions,and abundant availability.Hence,research into and applications of olfactory stimulation in improving cognitive dysfunction have raised widespread concerns.This article reviews the rela-tionship between the olfactory pathway and cognitive brain regions,and explores the mechanism by which natural plant es-sential oils alleviate cognitive dysfunction through olfactory stimulation in order to provide a reference for improving cogni-tive function via olfactory stimulation.

Objective To study the influence of rosemary essential oil inhalation on the memory of mice experiencing sleep deprivation and to delineate the possible mechanisms involved.Methods C57BL/6J mice were randomly divided into four experimental groups in this study:a control group(Con),a control group with rosemary essential oil inhalation(Con+REO),a sleep deprivation group(SD)and a sleep deprivation group with rosemary essential oil inhalation(SD+REO).A 72-hour sleep deprivation model was induced using the multiple platform water environment method,with the Con+REO and SD+REO groups exposed to rosemary essential oil inhalation.Cognitive function was evaluated through Y-maze and novel object recognition tests.The hippocampal tissue was analyzed for superoxide dismutase(SOD)activity and the concentrations of malondialdehyde(MDA)and glutathione(GSH).ELISA was used to determine the levels of norepinephrine(NE),dopamine(DA),and serotonin 5-hydroxytryptamine(5-HT)in the hippocampus.The expression levels of postsynaptic density 95(PSD95)and brain-derived neurotrophic factor(BDNF)in the hippocampus were determined using immunoblotting techniques.Results Compared with the Con and Con+REO groups,the SD group demonstrated a significant reduction in the spontaneous alternation percentage in the Y-maze as well as the novel object recognition index.Additionally,there was a pronounced decrease in hippocampal SOD activity and GSH content,a substantial elevation in MDA levels,and a decrease in the levels of DA,NE,and 5-HT.The expressions of PSD95 and BDNF proteins also decreased.In comparison with the SD group,the SD+REO group exhibited a significant increase in the spontaneous alternation percentage in the Y-maze and the novel object recognition index.There was also a marked increase in hippocampal SOD activity and GSH content,a reduction in MDA levels and elevated levels of NE and DA.Moreover,the expressions of PSD95 and BDNF proteins were upregulated.Conclusion The inhalation of rosemary essential oil enhances the memory of sleep-deprived mice,and the underlying mechanism may involve the mitigation of oxidative stress within the hippocampal tissue,the modulation of neurotransmitter levels,and the facilitation of synaptic plasticity.

Objective:To investigate the role and mechanism of dopamine receptor D2(DRD2)in the immune microenvironment of breast cancer. Methods:The xenograft model of breast cancer is established using female C57BL/6J mice and murine breast cancer EO771 cells.Mice with transplanted tumor were treated by intraperitoneal injection of the specific antagonist of DRD2,thioridazine,while PBS was injected intraperitoneally in the control group.siDRD2 targeting DRD2 gene was intratumorally injected to tumor-bearing mice[negative control siRNA(siNC)was injected to the control group].The percentage of Ki-67 positive cells and CD4+T lymphocytes in tumor tissue was examined by immunohistochemical analysis.The proportion of CD45+CD4+T lymphocytes,CD45+CD4+IFNγ+Th1 cells and CD45+CD4+IL-1 7+Th17 cells was detected by flow cytometry. Results:Compared with the control group,the tumor volume(P＜0.05),tumor mass(P＜0.001)and the proportion of Ki-67 positive cells(P＜0.001)in tumor tissue were decreased in the thioridazine-treated group.The proportion of CD45+immune cells(P＜0.05)and CD4+T lymphocytes(P＜0.001)in thioridazine-treated group was higher than that in the control group.The proportion of Th1 cells(CD45+CD4+IFNγ+)increased(P＜0.001)in thioridazine-treated group.There was no significant changes in the proportion of Th1 7 cells(CD45+CD4+IL-1 7+)(P＞0.05).Compared with the control group(siNC),the tumor volume(P＜0.05),tumor mass(P＜0.001)and the proportion of Ki-67 positive cells(P＜0.001)were decreased in siDRD2 group.The proportion of tumor infiltrating CD4+T lymphocytes(P＜0.001)and Th1 cells(P＜0.001)in the siDRD2 group was higher than that in the siNC group,whereas the change in the proportion of Th1 7 cells was not statistically significant(P＞0.05). Conclusion:Down-regulation of DRD2 could promote the differentiation of Th1 cells and inhibit the proliferation of breast cancer cells in a mouse breast cancer model.

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.