Objective:To investigate the relationship between lifestyle factors and stroke in the elderly.Methods:Data were obtained from a natural cohort of the Multimodal Intervention to Delay Dementia and Disability in Rural China(MIND-China)study.A total of 5 009 participants aged 60 years and above were enrolled, of whom 954(19.05%)had experienced a stroke.Logistic regression analyses were conducted to assess the association between five lifestyle factors(smoking, drinking, physical exercise, social activity and sleep quality)and the incidence of stroke.Results:In model 1, after adjusting for age, sex and education, only social activity( OR=0.783, 95% CI: 0.668-0.917)and good sleep quality( OR=0.731, 95% CI: 0.621-0.860)emerged as protective factors against stroke(both P<0.05).No statistically significant associations were found between other lifestyle factors and stroke.Analysis of a variety of healthy lifestyle practice combinations showed that having 3( OR=0.639, 95% CI: 0.433-0.944), 4( OR=0.620, 95% CI: 0.409-0.941)and 5( OR=0.397, 95% CI: 0.197-0.799)healthy lifestyle practices were protective factors against stroke(all P<0.05).In model 2, after adjusting for age, sex, education, body mass index, diabetes, hyperlipidemia, hypertension, and the APOE genotype, the results were consistent with those of Model 1. Conclusions:Lifestyle factors are significantly associated with the risk of stroke in the elderly population.The healthier lifestyle practices are adopted, the lower the risk of stroke will be.

Alzheimer disease(AD)is a common neurodegenerative disease characterized by cognitive decline and is the most common cause of dementia in the elderly.At present,the pathogenesis of AD remains unclear,and there is still a lack of effective treatment methods for etiologies.Apolipoprotein E(APOE)is currently the only risk gene recog-nized for AD,and the ApoE protein encoded by ApoE plays an important role in the pathological processes of AD,such as amyloid β-protein deposition,excessive phosphorylation of tau protein,and neuroinflammatory reaction.This article re-views the structure and function of ApoE and its role in the pathological processes of AD,in order to provide ideas and di-rections for finding new intervention targets for AD.

Objectives:To analyze and compare the disease burden of ischemic stroke due to tobacco exposure (including active and passive smoking) and its changing trends in China from 1990 to 2019,and to provide a reference for precise prevention and control of ischemic stroke. Methods:Based on the Global Burden of Disease Study 2019 database,we analyzed the burden of ischemic stroke disease attributable to tobacco exposure and its trends in different age and sex populations in China from 1990 to 2019,and compared the epidemiological differences in the burden of ischemic stroke disease attributable to active versus passive smoking. Results:Between 1990 and 2019,the disease burden of ischemic stroke attributable to tobacco exposure showed a decreasing trend in China and globally,but the decrease was relatively small in China.In 2019,the age-standardized mortality rate (ASMR) and age-standardized disability-adjusted life-year rate (ASDR) of ischemic stroke attributable to tobacco exposure in China were 10.64/100000 and 239.39/100000,both higher than the global average levels (5.85/100000 and 140.23/100000 respectively).The actual mortality and disability-adjusted life year (DALY) rates for ischemic stroke due to tobacco exposure in 2019 increased by 103.79％ and 90.48％,respectively,compared with 1990.There was a sex difference in the disease burden of ischemic stroke due to active and passive smoking,with the number of deaths,mortality,DALY,and DALY rates for ischemic stroke due to active smoking being significantly higher in men than in women.Conversely,the burden of ischemic stroke due to passive smoking was higher in women.At the age level,ischemic stroke attributable to both active and passive smoking presented the highest number of deaths,mortality,and DALY rates among those ≥70 years of age.Whereas DALY for ischemic stroke attributable to active smoking was mainly concentrated in those aged 50-69 years,DALY for ischemic stroke attributable to passive smoking was mainly concentrated in those aged ≥70 years. Conclusions:The disease burden of ischemic stroke attributable to tobacco exposure is higher in China than the global average level.The burden of ischemic stroke disease attributable to active and passive smoking varies significantly by sex and age,and more targeted tobacco control policies should be developed in China.

As a prescription for tonifying kidney yang， Youguiwan accords with the pathogenesis of osteoarthritis. Professor LIU Yuan-lu from the Affiliated Hospital of Liaoning University of Traditional Chinese Medicine found that modified Youguiwan had a significant effect on the clinical conservative treatment of osteoarthritis pain with Chinese medicine. There are teams studying the mechanism of Youguiwan in the treatment of osteoarthritis in China， but the profound study of the compound needs the mechanism of each component as support. Youguiwan contains 10 kinds of Chinese medicine， including Rehmanniae Radix Praeparata， Aconiti Lateralis Radix Praeparata， Cinnamomi Cortex， Dioscoreae Rhizoma， Corni Fructus， Cuscutae Semen， Angelicae Sinensis Radix， Eucommiae Cortex， Cervi Cornus Colla， and Lycii Fructus. With more and more attention to the study of Chinese medicine monomer， the amount of related research in this field is increasing. Therefore， it is of great significance to summarize the mechanism of Youguiwan in the treatment of osteoarthritis. Based on the sovereign， minister， assistant， and guide of Chinese medicine in Youguiwan， this paper used China National Knowledge Infrastructure （CNKI）， Pharmacopoeia of the People's Republic of China （2020 edition Vol. 1）， and ChemicalBook platform to understand the active components of each kind of Chinese medicine， and used PubMed to search. The latest research progress of effective monomers that had an intersection with the mechanism of osteoarthritis was summarized， and there were five pharmacological effects including anti-inflammation， pain inhibition， chondrocyte apoptosis， oxidative stress， and extracellular matrix degradation， involving several signaling pathways. The theory of sovereign， minister， assistant， and guide and the molecular mechanism were integrated and discussed， respectively， and finally， they were combined with traditional Chinese medicine theory， providing theoretical references for further study in this direction.

Objective:To explore the relationship between constitutional types of Chinese medicine and Alzheimer's disease (AD) and to construct an early warning model for AD risk.Methods:In the established multimodal interventions to delay dementia and disability in rural China (MIND-China) study, 4 033 elderly subjects aged ≥60 years old were included. The data including demographic, underlying disease and neuropsychological data were collected.The Chinese medicine service record form for the elderly was used to assess constitutional types of Chinese medicine and to apply the NIA-AA diagnostic criteria published by the National Institute on Aging and the Alzheimer's Association in 2011 for the diagnosis of clinically likely AD. Logistic regression analysis and AD risk prediction models were constructed using R statistical software, and the final prediction results were presented using columnar plots.Results:The MIND-China cohort was dominated by the abnormal constitution (69.28%), of which Phlegm-wetness type was the most common (58.05%), followed by Yang-deficiency type (23.85%). The most constitutional type of Chinese medicine among AD patients was Phlegm-wetness type (54.35%), followed by Qi-depression type (38.04%). Multi-factorial logistic regression analysis suggested that increasing age ( β=0.101, P<0.001, OR=1.107, 95% CI=1.069-1.146) and Qi-depression type ( β=0.622, P=0.016, OR=1.862, 95% CI=1.116-3.076) were able to increase the risk of developing AD, while education ( β=-1.047, P<0.001, OR=0.351, 95% CI=0.205-0.584) was able to reduce the risk of developing AD. By using the risk score model to calculate the total risk score for each subject and plotting the receiver operating characteristic curve (ROC), the area under the ROC was 0.769 and the calibration curve showed excellent consistency between prediction and reality. Conclusion:Older adults with Qi-depression type are significantly associated with an increased likelihood of AD.

OBJECTIVETo evaluate the role of germline mutations of TP53 gene among a Chinese population with high risk for breast cancer.

METHODSA total of 81 BRCA-negative breast cancer probands from cancer families were analyzed using targeted capture and next-generation sequencing. Candidate mutations were verified with Sanger sequencing. Co-segregation analyses were carried out to explore the likely pathogenicity of the mutation.

RESULTSOf the 81 BRCA-negative patients, 3 exonic mutations in the TP53 gene were identified in 3 breast cancer patients. Of these, 2 mutations were previously reported and 1 was novel. One family with TP53 mutation has met the criteria for Li-Fraumeni syndrome (LFS) and accounted for 9.1% of all families who fulfilled the diagnostic criteria for LFS. Two of the carriers were diagnosed with breast cancer under the age of 30, and have accounted for 11.8% (2/17) of all very young (≤30 years) breast cancer patients in our study.

CONCLUSIONThe TP53 germline mutation is more common in Chinese population with a high risk for breast cancer than previously thought. TP53 gene mutation screening should be considered particularly for patients with a family history of LFS and very young age of onset.

Adult ; Asian Continental Ancestry Group ; genetics ; Base Sequence ; Breast Neoplasms ; ethnology ; genetics ; China ; DNA Mutational Analysis ; Exons ; Family Health ; Female ; Genetic Predisposition to Disease ; ethnology ; genetics ; Germ-Line Mutation ; Heterozygote ; Humans ; Li-Fraumeni Syndrome ; ethnology ; genetics ; Male ; Middle Aged ; Pedigree ; Risk Factors ; Tumor Suppressor Protein p53 ; genetics ; Young Adult

Objective To study the correlation between structure of b D -glucan derivatives from Poria cocos sclerotiuma and anti gastric cancer activities of elderly rats.Methods A water insoluble (1→3)-β-D-glucan (PCS3-Ⅱ ) isolated from fresh sclerotium of Poria cocos was sulfated,carboxymethylated,methylated,hydroxyethylated and hydroxypropylated,respectively,to prepare five water-soluble derivatives.Their activities of the native β-glucan and five derivatives against gastric cancer cell strains of MKN-45,SGC 7901and MKN-28 were tested in vitro and in vivo.Results The native β-glucan did not show any anti-gastric cancer activity,while the sulfated and carboxymethylated derivatives significantly exhibited the anti gastric cancer activity against MKN-45,SGC-7901 and MKN-28 cells in vitro,and elderly rats with MKN-45 transplanted tumor,especially.The gastric cancer inhibition rates of elderly rats were 32.7％ and 36.4％ for the 100 mg/kg sulfated and carboxymethylated derivatives,respectively.Conclusions The fresh sclerotium of Poria cocos polysaccharides can not show any anti gastric cancer activity in vitro,but the sulfated and carboxymethylated derivatives may increase the inhibition effect.Water-solubility,higher chain stiffness and relatively molecular weight would be benefit to increase anti-elderly gastric cancer activity of polysaccharides from Poria cocos sclerotiuma.

BACKGROUND: There are plenty of studies of estrogen effects on mammalian osteoblast, but the studies of estrogen effects on bird osteoblast cannot be found. There are many reports about the side effects of letrozole on bone metabolism, but there are no reports about the effect of letrozole on osteoblast.OBJECTIVE: The effects of estrogen and letrozole on the proliferation, cell cycle, estrogen receptor mRNA expression and alkaline phosphatase (ALP) activity of chicken osteoblast in vitro were studied in order to illustrate the mechanism of medullary bone osteogenesis.METHODS: The osteoblasts were harvested from the frontal bone of 15-day SPF chicken embryos by the enzyme digestion, and treated with various mass concentrations of estrogen (0, 5, 10, 20, 100. 200, 400,800, 2 000, 20 000 ng/L) and letrozole (0, 5.10, 25, 50, 100, 250, 500, 1 000, 5 000 μg/L). The proliferation rates of the osteoblast treated with estrogen or letrozole were measured through the MTT method, The ALP activities of osteoblast were measured by the pNPP method. The cell cycle was measured by flow cytometry. The expression of estrogen receptor mRNA was detected using real-time fluorescent quantitative polymerase chain reaction (PCR).RESULTS AND CONCLUSION: The estrogen could promote proliferation of osteoblast in concentration- and time-dependent fashion. Estrogen could increase the expression of estrogen receptor mRNA, impulse cell cycle, and elevate ALP activities.Letrozole could increase the cell population, impulse cell cycle, inhibit estrogen receptor mRNA expression, but letrozole has no effects on ALP synthesis and secretion.

Objective To report a familial dentinogenesis imperfecta type Ⅱ (DGI type Ⅱ) with a novel splicing mutation in DSPP (dentin sialophosphoprotein) gene.Methods Based on the result of linkage analysis performed previously to map the candidate gene DSPP in the family, the promoter,the first four exons and exon-intron boundaries of DSPP were directly sequenced for the members of the DGI type Ⅱ family. Denaturing high performance liquid chromatography (DHPLC) analysis was performed to confirm the results of sequencing.Results A novel splicing mutation of 23 bp deletion in intron 2 of DSPP gene was identified by DNA sequence analysis. The mutation changed acceptor site sequence from CAG to AAG, and might result in functional abolition of possible branch point site in intron 2. DHPLC result was consistent with that of sequencing. The mutation may be identified in all affected individuals, but not found in normal members of the family and 50 controls.Conclusion These results suggest the deleted mutation of DSPP gene causes DGI type Ⅱ in the family. The mutation has not been reported before.

The abilities of self-study,thinking and communication are much more emphasized in the problem based learning(PBL)than in the conventional curriculum.From the view of the inherent relationship between the ability training and PBL,this paper probes into the characteristics of PBL to find the way of fitting the situation of our country.It is essential to the successful teaching and training more high quality students.