Objective To explore the relationship between blood pressure at baseline and significant decline in cognitive function after 4 years in middle-aged and elderly people in rural Xi'an,and the potential effect of age on the relationship.Methods Data were collected from a cohort of middle-aged and elderly people with cognitive impairment in rural Xi'an,Shaanxi Province.The cohort consisted of people aged≥40 years from a village in Huyi District,Xi'an.The baseline survey was completed between October 2014 and March 2015,and two follow-up visits were conducted in 2016 and 2018.Blood pressure parameters studied included hypertension and high systolic blood pressure(≥140 mmHg vs.＜140 mmHg),and high diastolic blood pressure(≥90 mmHg vs.＜90 mmHg).The Mini-Mental State Examination(MMSE)was used to assess the whole cognitive function,and the decline of MMSE score ≥4 points in 4 years was defined as significant decline of cognitive function.Multivariate Logistic regression was used to analyze the relationship between blood pressure and cognitive function at baseline.Subgroup analysis was used to study the effect of age(＜65 vs.≥65 years)on the relationship.Results We recruited a total of 1 350 subjects in the analysis,including 235 subjects(17.4％)with baseline age ≥65 years and 533 male subjects(39.5％);671 subjects(49.7％)had hypertension,with systolic blood pressure of(131.71±17.79)mmHg;840 subjects(62.2％)had high systolic blood pressure,with diastolic blood pressure of(82.18±10.56)mmHg;395(29.3％)had high diastolic blood pressure.During the 4-year follow-up,56 cases(4.2％)met the criteria for significant decline of cognitive function.We did not find significant association of hypertension and high systolic blood pressure with cognitive decline in the general population,＜65-year-old subgroup,or ≥ 65-year-old subgroup.The incidence of significant cognitive decline was not statistically significant in the total population(3.6％vs.5.6％,P=0.092),the ≥65-year-old subgroup(7.5％vs.8.2％,P=0.855),the normal diastolic blood pressure group,or the high diastolic blood pressure group.However,in the subgroup＜65 years,the incidence of cognitive decline was higher in the high diastolic blood pressure group than in the normal diastolic blood pressure group(2.7％vs.5.1％,P=0.043).Multivariate analysis showed that high diastolic blood pressure was not found to be associated with significant cognitive decline in the total population(OR=1.744,95％CI:0.953-3.192,P=0.071),the subgroup of ≥65 years old(OR=0.858,95％CI:0.221-3.338,P=0.825),or the subgroup of ≥65 years old.In the＜65 age group,high diastolic blood pressure was significantly associated with cognitive decline(OR=2.051,95％CI:1.005-4.186,P=0.048).Conclusion High diastolic blood pressure is associated with 4-year cognitive decline in people aged 40-65 years,but not in those aged ≥65.No association is found between hypertension or high systolic blood pressure and significant cognitive decline.

Objective By comparing the prevalence and mortality of dementia among rural people in Xi'an in 1997 and 2014 to clarify the epidemiological changes of dementia among rural people in the city over 17 years.Methods In 1997 and 2014,people aged 55 and above in villages in Xi'an were selected by random cluster sampling method,and face-to-face questionnaire survey was conducted by combining centralized and home visits.Dementia and its subtypes were diagnosed by"the three-step method";the changes of dementia prevalence and mortality were compared between the two surveys.Results The prevalence of dementia among rural residents aged 55 and above in Xi'an was 3.49％in 1997,with age-gender standardized prevalence of 2.08％.In 2014,the prevalence of dementia was 4.25％,with age-gender standardized prevalence of 2.78％.Over the 17 years,the prevalence of dementia increased by 1.79 times(OR=1.79,95％CI:1.20-2.65,P=0.004),with a 1.9-fold increase in females and a 1.67-fold increase in males.The mortality of dementia patients was 61.76‰ and age-gender standardized mortality was 60.20‰ in 1997,while the mortality was 35.71‰ and age-gender standardized mortality was 34.18‰ in 2014.The mortality of dementia decreased by 33％over the 17 years(HR=0.33,95％CI:0.15-0.74,P=0.007).Conclusion The prevalence of dementia in rural areas of Xi'an increased significantly over the 17 years,but the mortality rate decreased,and this trend was more obvious in women.

Objective To investigate the relationship between type 2 diabetes mellitus(T2DM)and cognitive decline.Methods Data were obtained from the cognitive impairment cohort of middle-aged and elderly population in rural areas of Xi'an City.The cohort consisted of residents aged 40 years and older in two villages of Huyi District,Xi'an.The baseline survey was completed between October 2014 and March 2015,with two follow-up visits in 2016 and 2018.The present study was conducted on cognitively normal people at baseline.Individual characteristics,lifestyle,and medical history were collected;physical and biochemical examinations were completed.According to medical history of T2DM and fasting blood glucose,the study population was divided into non-T2DM group,pre-existing T2DM group,and new-onset T2DM group.The Mini-Mental State Examination(MMSE)was used to assess global cognitive function.Participants with a drop of≥2 points in MMSE score from baseline after 4 years were defined as having cognitive decline.Chi-square test and multivariate Logistic regression analysis were employed to analyze the effect of T2DM status on the risk of cognitive decline.Results A total of 1 350 subjects completed the follow-up.In the follow-up population,1 096(81.2％)were free of T2DM,158(11.7％)already had T2DM at baseline,and 96(7.1％)developed new-onset T2DM during the follow-up.Cognitive decline was observed in 230 individuals after 4 years,representing 17.0％of the study population.The new-onset T2DM group had the highest 4-year incidence of cognitive decline(non-T2DM group vs.pre-existing T2DM group vs.new-onset T2DM group:15.7％vs.20.9％vs.26.0％,P=0.014),and the incidence of cognitive decline in the newly-onset T2DM group was significantly higher than that in the non-T2DM group(P=0.009).Multivariate Logistic regression analysis showed that the new-onset T2DM group had an increased risk of cognitive decline compared with the non-T2DM group within 4 years(OR=1.726,95％CI:1.029-2.896,P=0.039).However,no significant difference in 4-year risk of cognitive decline in the pre-existing T2DM group was observed(OR=1.402,95％CI:0.890-2.210,P=0.145).Conclusion Through the 4-year follow-up study of cognitively normal adults aged 40 and above in rural Xi'an,it was found that new-onset T2DM patients face a significantly elevated risk of cognitive decline,suggesting that cognitive decline may occur in the early stage of T2DM.

Objective To explore the relationship between plasma amyloid-β(Aβ)and cognitive impairment.Methods A total of all villagers(aged 40 years and above)from two villages of Xi'an,China,were enrolled.A validated Chinese version of the Mini-Mental State Examination and neuropsychological battery were used to assess cognition.Levels of fasting plasma Aβ1-42 and Aβ1-40 were tested using commercial enzyme-linked immunosorbent assay(ELISA).Relationship between plasma Aβ and cognitive impairment was analyzed using Logistic regression analysis.Results Of the 1 314 enrolled subjects,1 180(89.80％)had normal cognition,85(6.47％)had suspected cognitive impairment,and 49(3.73％)had probable cognitive impairment.Univariate analysis showed that plasma Aβ1-42/Aβ1-40 ratio was higher in the suspected cognitive impairment group than in the probable cognitive impairment group(P＜0.05)and normal cognitive group(P＜0.05);plasma Aβ1-42 level in the suspected cognitive impairment group was higher than that in normal cognitive group(P＜0.05).The level of Aβ1-40 did not differ between the three groups.After correcting for confounding factors(including age,gender,degree of education,cognitive impairment risk factors,habits of living)in the multivariate Logistic regression analysis,the results were consistent with those in the univariate analysis.Conclusion Levels of plasma Aβ1-42 and Aβ1-42/Aβ1-40 ratio were elevated in patients with suspected cognitive impairment,indicating that elevated plasma Aβ1-42 and Aβ1-42/Aβ1-40 ratio may be more pronounced in early stage of cognitive impairment.They may be early biomarkers for cognitive impairment,which can help identify and intervene the disease earlier.

Objective To explore the relationship between carotid atherosclerosis(CAS)and cognitive impairment in the stroke high-risk population aged 40 years and above in the rural area of Xi'an City and determine whether CAS is a risk factor for cognitive impairment.Methods In this study,stroke high-risk population found in the Community and Rural Population Stroke High-risk Group Screening and Intervention Project carried out in Huyi District,Xi'an City,from October 2014 to March 2015 were selected as the research subjects.Color Doppler ultrasound was used to evaluate CAS,and CAS was defined as:carotid intima-media thickness(CIMT)≥1.0 mm,or carotid arteries(including common carotid artery,carotid sinus,internal carotid artery,and external carotid artery)have atherosclerotic plaques,or carotid stenosis.Mini-Mental State Examination(MMSE)was used to assess cognitive function.The MMSE score lower than the cut-off value(illiteracy ≤17,primary school ≤ 20 points,and junior high school and above education level ≤24 points)is defined as cognitive impairment.The study population was grouped according to the presence of CAS or cognitive impairment;univariate difference test and bivariate logistic regression were used to analyze the relationship between CAS and cognitive impairment.Results A total of 451 subjects were included in the analysis.The average age of the subjects was(58.7±9.83)years old,and 44.3％were female.Among them,329 cases(72.9％)had CAS and 57 cases(12.6％)met the diagnostic criteria for cognitive impairment.The prevalence of cognitive impairment in CAS group was significantly higher than that in non-CAS group(14.6％vs.7.4％,P=0.041).Multivariate logistic regression analysis showed that cognitive impairment was significantly correlated with age(OR=1.121,95％CI:1.056-1.189,P＜0.001),but not with CAS(OR=1.008,95％CI:0.202-5.170,P=0.992).Conclusion No significant association between CAS and cognitive impairment was found in high stroke risk group aged 40 and above in rural areas of Xi'an.

Objective To investigate the correlation between coronary heart disease(CHD)and cognitive impairment in rural populations aged 40 and above.Methods From October 2014 to March 2015,all residents aged 40 and above from two villages in Huyi District,Xi'an,were selected as study subjects.Information regarding their demographics,lifestyle habits,medical history,family history,physical examinations,and biochemical tests was collected.The participants were categorized into those with and without the history of CHD.Cognitive function was assessed using the Mini-Mental State Examination(MMSE),with scores below the cutoff(illiteracy≤17;primary school≤20;junior high school and above≤24)defined as cognitive impairment.Chi-square test was used to compare the prevalence of cognitive impairment between the CHD and non-CHD groups.Multivariate Logistic regression was employed to adjust for confounding factors in analyzing the relationship between CHD and cognitive impairment.Results A total of 1 833 subjects were included in the analysis,comprising 735 males(40.1％)and 57 individuals with CHD(3.1％).Among them,234 participants(13.3％)met the criteria for cognitive impairment.Univariate analysis showed a higher prevalence of cognitive impairment in the CHD group compared to the non-CHD group(24.6％vs.12.9％,P=0.016).Unadjusted binary Logistic regression analysis indicated a positive correlation between CHD and cognitive impairment(OR=2.199,95％CI:1.185-4.084,P=0.013).However,after adjusting for confounding factors such as gender,age,education level,hypertension,diabetes,dyslipidemia,stroke history and BMI,the association between CHD and cognitive impairment was not statistically significant(OR=1.265,95％CI:0.656-2.441,P=0.483).In the stratified analysis,among diabetic patients,CHD was significantly associated with a high risk of cognitive impairment(OR=4.191,95％CI:1.464-12.000,P=0.008).The prevalence of cognitive impairment significantly increased in patients with CHD combined with diabetes(OR=4.712,95％CI:1.651-13.449,P=0.004).Conclusion This study did not establish a direct association between CHD and cognitive impairment.However,this study suggests that the presence of CHD and diabetes mellitus is significantly associated with an increased risk of cognitive impairment.Future prospective studies with larger sample sizes should be conducted to further confirm the relationship between the two.

Objective To analyze the relationship between apolipoprotein E(APOE)genotype and cognitive impairment among individuals aged 40 and above in rural Xi'an and to explore the potential influence of education on this relationship.Methods All permanent residents aged 40 and above from two villages in Huyi District,Xi'an City,were selected as research subjects,employing a cross-sectional survey approach.The Mini-Mental State Examination(MMSE)was utilized to assess overall cognitive function,with MMSE scores below the threshold values(illiterate ≤17,primary school ≤20,junior high and above ≤24)considered as cognitive impairment.Fasting elbow venous blood was drawn in the morning,and the APOE genotype was determined.The population was divided into low-education(LE,≤9 years)and high-education(HE,＞9 years)groups based on educational level.Univariate and multivariate analyses were applied to explore the association between APOE genotype and cognitive impairment,as well as MMSE scores in both the total and stratified populations.Results Out of the 1 692 participants,there were 263 APOE ε4 allele carriers(E2/4,E3/4,E4/4)(15.3％),and 205 individuals met the criteria for cognitive impairment(12.1％).Multivariate Logistic regression and linear regression analyses revealed that in both the total population and the LE population,compared to APOE ε4 allele non-carriers(E2/2,E2/3,E3/3),APOE ε4 allele carriers exhibited a higher risk of cognitive impairments(total population:OR=1.509,95％CI:1.030-2.211,P=0.035;LE:OR=1.604,95％CI:1.080-2.381,P=0.019),and their MMSE scores were lower(total population:β=-0.053,95％CI:-0.983--0.162,P=0.006;LE:β=-0.052,95％CI:-1.052--0.124,P=0.013).However,in the HE population,there was no statistically significant difference in the prevalence of cognitive impairment(OR=1.883,95％CI:0.254-13.980,P=0.536)and MMSE scores(β=0.001,95％CI:-0.635-0.642,P=0.992)between APOE ε4 allele carriers and non-carriers.Conclusion The APOE ε4 allele was associated with an increased risk of cognitive impairment in individuals aged 40 and above in rural areas of Xi'an,while HE attainment may offer protective effects against cognitive impairment in APOE ε4 allele carriers.

Objective To develop a risk predictive model of cognitive decline in a prospective cohort study in rural area of Xi'an and compare the predictive performance with that of the classical CAIDE model.Methods The cohort was established between October 2014 and March 2015 in two selected villages in rural Xi'an.Mini-Mental State Examination(MMSE)was applied to assess global cognition at baseline and 4-year follow-up,and cognitive decline was defined as a drop of ≥4 points in MMSE after 4-year follow-up.Participants were randomly split into training set and validation set in a ratio of 7∶3.The Logistic regression analysis was used to develop the predictive model,and the area under the receiver operating characteristic(ROC)curve was applied to assess the performance of the risk model.Results Occurrence of cognitive decline after 4-year follow-up was 4.15％.Future cognitive decline was significantly predicted by age,low education and stroke(AUC in training set=0.73,95％CI:0.63-0.79;AUC in valid data=0.77,95％CI:0.67-0.87),while the classical CAIDE model did not predict the risk of cognitive decline well(AUC=0.68,95％CI:0.61-0.75).The results differed after stratification by APOE genotype,and showed a better predictive value of both our model(AUC=0.87,95％CI:0.78-0.96)and CAIDE model(AUC=0.89,95％CI:0.81-0.98)in APOE ε4 carriers.Conclusion The predictive model was developed based on age,educational level and stroke,and it predicted relatively well 4-year cognitive decline as compared with traditional CAIDE model,especially in APOE ε4 carriers.However,the model should be validated after longer follow-up and further improved to increase its predictive value.

Aim To investigate the effects of sodium lactate(NALA)on right heart failure induced by monocrotaline(MCT)-induced pulmonary arterial hy-pertension in rats and to reveal the underlying mecha-nisms.Methods Forty male Sprague-Dawley(SD)rats were randomly allocated into four groups,with ten rats in each group,namely,MCT group,NALA group,and NALA+MCT group;the MCT and NALA+MCT groups were administered a single intraperito-neal injection of MCT at 60 mg·kg-1 to induce pul-monary hypertension,and one week later,the NALA and NALA+MCT groups received intraperitoneal in-jections of NALA at 0.1 g·kg-1(once a day,for 5 weeks),while the CON and MCT groups received e-qual volumes of physiological saline(once a day,for 5 weeks);right heart function was assessed using echo-cardiography,right ventricular and pulmonary artery remodeling were evaluated via histopathological sec-tions,and the expression levels of ANP,BNP,and in-flammatory factors were measured by ELISA,along with assessments of oxidative stress levels,Western blot detection of the expression levels of proteins in the TLR4/NF-κB signaling pathway.Results Compared to the CON group,the MCT group exhibited increased RVSP and RVHI,decreased right heart function,in-creased collagen fiber deposition,and elevated oxida-tive stress and inflammatory factor expression,and the expression levels of proteins in the TLR4/NF-κB signa-ling pathway increased(P＜0.05);compared to the MCT group,the NALA+MCT group showed reduced RVSP and RVHI,improved right heart function,atten-uated pulmonary vascular remodeling,decreased ex-pression of ANP,BNP,inflammatory factors,and H2O2,along with increased antioxidant enzyme expres-sion,and the expression levels of proteins in the TLR4/NF-κB signaling pathway decreased(P＜0.05).Conclusion NALA can inhibit right ventric-ular remodeling in rats with pulmonary hypertension,and the underlying mechanism may involve the allevia-tion of inflammatory responses and oxidative stress through the inhibition of the TLR4/NF-κB signaling pathway.

Viruses,with high adaptability and immune evasion capabilities,are responsible for a wide spectrum of diseases from lo-calized infections to global pandemics,continuously posing threats to global public health.In recent years,traditional Chinese medi-cine(TCM)has demonstrated significant potential in antiviral therapy.With its multi-component,multi-target synergistic mechanism,TCM offers unique advantages in the intervention of viral diseases.However,progress in elucidating the active antiviral constituents of TCM and identifying their precise molecular targets remains limited,primarily due to the lack of humanized models that can faithfully recapitulate the natural course of viral infection.The emergence of organoid technology has introduced new opportunities for antiviral research in TCM.Human organoids,which recapitulate the three-dimensional architecture and physiological functions of human tis-sues,provide an advanced platform for modeling host-virus interactions in a human-relevant context.This article highlights the latest advances in applications of human tissue organoids,including lung,liver,and brain organoids,in the study of respiratory viruses(SARS-CoV-2,influenza virus,respiratory syncytial virus),hepatitis viruses(HBV,HCV,HEV),and neurotropic viruses(ZIKV,pri-ons,HCMV);illustrates how organoid models have been leveraged to evaluate both the efficacy and safety of TCM-based antiviral inter-ventions.Although human tissue organoids still face technical challenges in insufficient vascularization and incomplete immune micro-environment,they represent a powerful tool for dissecting the mechanism of TCM antiviral action and for guiding the development of personalized antiviral strategies.Looking ahead,human tissue organoid technology is expected to become key enabling platform for pro-moting the clinical transformation of TCM in the field of antiviral medicine.