Objective:To explore the association between cardiometabolic multimorbidity(CMM), the number of cardiometabolic diseases(CMD)and mild cognitive impairment(MCI)among the older adults in urban communities.Methods:Based on the baseline data of the Hubei Memory and Aging Cohort Study(HMACS)from 2018 to 2023, CMM was defined as the coexistence of two or more CMDs(Type 2 diabetes, stroke and ischemic heart disease). Multivariate logistic regression was employed to examine the association between CMM, the number of CMDs and the prevalence of MCI, as well as subgroup heterogeneity.Results:This study included 6 113 urban participants aged ≥65 years(55.6% were female; mean age 71.9±5.7 years). The prevalence of MCI was 19.3%, with an increasing trend observed as the number of CMD increased(17.7%, 20.5%, 24.6%, 28.3%). After adjusting for all variables, a significant association was observed between CMM group and the prevalence of MCI( OR: 1.24, 95% CI: 1.01-1.52)compared with the non-CMM group.As the number of CMD increased, the prevalence of MCI increased( Ptrend=0.011), but the association was only significant in the group with two CMDs.Subgroup analyses revealed that in males( OR: 1.48, 95% CI: 1.10-2.00), those with more than 9 years of education( OR: 1.52, 95% CI: 1.15-2.02), and those with hypertension( OR: 1.33, 95% CI: 1.05-1.67), CMM was significantly associated with MCI, and the association with MCI increased significantly with the increase in the number of CMDs(all Pfor trend <0.05). Conclusions:Among urban community-dwelling older adults aged ≥65 years in China, CMM and the cumulative number of CMDs are significantly associated with an increase of MCI, particularly in males, those with higher education levels, and those with hypertension.In the future, the need for enhanced MCI screening for CMM patients should be strengthened, and targeted prevention and control of cognitive impairment should be implemented for high-risk populations.

Drug-induced liver injury(DILI)is one of the major challenges in drug development and clinical practice,and effective prevention and con-trol measures remain lacking.Research has shown that DILI is primarily mediated by immune respons-es.Human leukocyte antigen(HLA)alleles are cur-rently the strongest genetic factors reported to be associated with DILI.Due to the low positive predic-tive value of HLA alleles,preemptive HLA genetic screening has limited clinical utility in preventing DILI.However,its high negative predictive value makes it valuable for DILI diagnosis and causality assessment.In recent years,polymorphisms in im-mune-related genes-such as those involved in anti-gen processing and presentation pathways,T-cell receptors,immunostimulatory molecules,and cyto-kines-have been found to be associated with DILI.Future studies combining these genes with HLA analysis may provide deeper mechanistic insights into DILI and facilitate their translational applica-tion in clinical practice,ultimately improving drug safety.

Lysine lactylation is a type of histone post-translational modification that is mainly regulated by fac-tors such as lactate level,glycolysis level,and vario us enzymes and proteins.Lysine lactylation involves several physio-pathological activities,including macrophage inflammatory response,somatic cell reprogramming,neuronal activity,and embryonic development,etc.Changes in the level of lactfication modification are involved in the development of neuropsy-chiatric disorders such as Alzheimer disease(AD),schizophrenia(SCZ)and depression.Inflammatory response and ab-normal neuronal activity are one of the important causes of neuropsychiatric diseases.The change of lactfication modifica-tion level participates in the development of AD,SCZ,depression and other neuropsychiatric diseases,which specifically regulate neuronal apoptosis,neuronal excitation,and microglial inflammatory response.

Lysine lactylation is a type of histone post-translational modification that is mainly regulated by fac-tors such as lactate level,glycolysis level,and vario us enzymes and proteins.Lysine lactylation involves several physio-pathological activities,including macrophage inflammatory response,somatic cell reprogramming,neuronal activity,and embryonic development,etc.Changes in the level of lactfication modification are involved in the development of neuropsy-chiatric disorders such as Alzheimer disease(AD),schizophrenia(SCZ)and depression.Inflammatory response and ab-normal neuronal activity are one of the important causes of neuropsychiatric diseases.The change of lactfication modifica-tion level participates in the development of AD,SCZ,depression and other neuropsychiatric diseases,which specifically regulate neuronal apoptosis,neuronal excitation,and microglial inflammatory response.

Drug-induced liver injury(DILI)is one of the major challenges in drug development and clinical practice,and effective prevention and con-trol measures remain lacking.Research has shown that DILI is primarily mediated by immune respons-es.Human leukocyte antigen(HLA)alleles are cur-rently the strongest genetic factors reported to be associated with DILI.Due to the low positive predic-tive value of HLA alleles,preemptive HLA genetic screening has limited clinical utility in preventing DILI.However,its high negative predictive value makes it valuable for DILI diagnosis and causality assessment.In recent years,polymorphisms in im-mune-related genes-such as those involved in anti-gen processing and presentation pathways,T-cell receptors,immunostimulatory molecules,and cyto-kines-have been found to be associated with DILI.Future studies combining these genes with HLA analysis may provide deeper mechanistic insights into DILI and facilitate their translational applica-tion in clinical practice,ultimately improving drug safety.

Objective To investigate the association between dietary behavior and mild cognitive impairment(MCI)in older adults,and to further analyze the role of cardiometabolic comorbidities in this relationship.Methods A total of 6599 older adults were recruited from 3 communities and 48 villages in Dawu County between 2018 and 2023 as part of the Hubei Elderly Memory Cohort Study.Dietary behaviors were assessed using a food frequency questionnaire and a dietary behavior questionnaire.Latent class analysis was performed to categorize the participants into healthy eat-ing behavior(HEB),sub-healthy eating behavior(SHEB),and unhealthy eating behavior(UEB).Cardiovascular-metabolic diseases were diabetes,hypertension,coronary heart disease,and cere-brovascular disease,which all diagnosed by physicians.MCI was diagnosed by a team of clinical experts according to Peterson's criteria.Multivariable logistic regression model was used to ana-lyze the impact of cardiometabolic comorbidities on the association between dietary behavior and MCI.Results The morbidity rate of MCI was 24.3％,and that of HEB,SHEB and UEB was 16.6％,24.3％and 31.3％,respectively.The incidence of MCI was higher in the participants who were female,over ≥75 years old,unmarried,and lack physical exercise,SHEB and UEB groups,had low educational level,lived in rural areas,had no stable income,had abnormal BMI,and more types of cardiometabolic diseases(P＜0.05,P＜0.01).After adjusting for confounders,multivari-able logistic regression analysis indicated that both UEB(OR=1.220,95％CI:1.004-1.418,P=0.045)and SHEB(OR=1.592,95％CI:1.345-1.883,P=0.001)were positively correlated with MCI risk in older adults.Further stratified analysis by cardiometabolic comorbidities revealed that for the patients in the HEB group,those suffering from hypertension+diabetes+coronary heart disease had the highest risk for MCI(OR=4.220,95％CI:1.913-9.309,P=0.001),while for the SHEB group,the following comorbidities were significantly associated with increased MCI risk:hypertension+diabetes(OR=1.640,95％CI:1.157-2.322,P=0.005),hypertension+cerebro-vascular disease(OR=1.454,95％CI:1.041-2.031,P=0.028),hypertension+diabetes+cere-brovascular disease(OR=2.064,95％CI:1.246-3.419,P=0.005),and hypertension+diabetes+coronary heart disease+cerebrovascular disease(OR=1.974,95％CI:1.036-3.760,P=0.039).Conclusion Older adults with SHEB or UEB have a higher risk of developing MCI,and the pres-ence of cardiometabolic comorbidities further exacerbates this risk.

Objective To investigate the association between dietary behavior and mild cognitive impairment(MCI)in older adults,and to further analyze the role of cardiometabolic comorbidities in this relationship.Methods A total of 6599 older adults were recruited from 3 communities and 48 villages in Dawu County between 2018 and 2023 as part of the Hubei Elderly Memory Cohort Study.Dietary behaviors were assessed using a food frequency questionnaire and a dietary behavior questionnaire.Latent class analysis was performed to categorize the participants into healthy eat-ing behavior(HEB),sub-healthy eating behavior(SHEB),and unhealthy eating behavior(UEB).Cardiovascular-metabolic diseases were diabetes,hypertension,coronary heart disease,and cere-brovascular disease,which all diagnosed by physicians.MCI was diagnosed by a team of clinical experts according to Peterson's criteria.Multivariable logistic regression model was used to ana-lyze the impact of cardiometabolic comorbidities on the association between dietary behavior and MCI.Results The morbidity rate of MCI was 24.3％,and that of HEB,SHEB and UEB was 16.6％,24.3％and 31.3％,respectively.The incidence of MCI was higher in the participants who were female,over ≥75 years old,unmarried,and lack physical exercise,SHEB and UEB groups,had low educational level,lived in rural areas,had no stable income,had abnormal BMI,and more types of cardiometabolic diseases(P＜0.05,P＜0.01).After adjusting for confounders,multivari-able logistic regression analysis indicated that both UEB(OR=1.220,95％CI:1.004-1.418,P=0.045)and SHEB(OR=1.592,95％CI:1.345-1.883,P=0.001)were positively correlated with MCI risk in older adults.Further stratified analysis by cardiometabolic comorbidities revealed that for the patients in the HEB group,those suffering from hypertension+diabetes+coronary heart disease had the highest risk for MCI(OR=4.220,95％CI:1.913-9.309,P=0.001),while for the SHEB group,the following comorbidities were significantly associated with increased MCI risk:hypertension+diabetes(OR=1.640,95％CI:1.157-2.322,P=0.005),hypertension+cerebro-vascular disease(OR=1.454,95％CI:1.041-2.031,P=0.028),hypertension+diabetes+cere-brovascular disease(OR=2.064,95％CI:1.246-3.419,P=0.005),and hypertension+diabetes+coronary heart disease+cerebrovascular disease(OR=1.974,95％CI:1.036-3.760,P=0.039).Conclusion Older adults with SHEB or UEB have a higher risk of developing MCI,and the pres-ence of cardiometabolic comorbidities further exacerbates this risk.

Objective:To explore the association between cardiometabolic multimorbidity(CMM), the number of cardiometabolic diseases(CMD)and mild cognitive impairment(MCI)among the older adults in urban communities.Methods:Based on the baseline data of the Hubei Memory and Aging Cohort Study(HMACS)from 2018 to 2023, CMM was defined as the coexistence of two or more CMDs(Type 2 diabetes, stroke and ischemic heart disease). Multivariate logistic regression was employed to examine the association between CMM, the number of CMDs and the prevalence of MCI, as well as subgroup heterogeneity.Results:This study included 6 113 urban participants aged ≥65 years(55.6% were female; mean age 71.9±5.7 years). The prevalence of MCI was 19.3%, with an increasing trend observed as the number of CMD increased(17.7%, 20.5%, 24.6%, 28.3%). After adjusting for all variables, a significant association was observed between CMM group and the prevalence of MCI( OR: 1.24, 95% CI: 1.01-1.52)compared with the non-CMM group.As the number of CMD increased, the prevalence of MCI increased( Ptrend=0.011), but the association was only significant in the group with two CMDs.Subgroup analyses revealed that in males( OR: 1.48, 95% CI: 1.10-2.00), those with more than 9 years of education( OR: 1.52, 95% CI: 1.15-2.02), and those with hypertension( OR: 1.33, 95% CI: 1.05-1.67), CMM was significantly associated with MCI, and the association with MCI increased significantly with the increase in the number of CMDs(all Pfor trend <0.05). Conclusions:Among urban community-dwelling older adults aged ≥65 years in China, CMM and the cumulative number of CMDs are significantly associated with an increase of MCI, particularly in males, those with higher education levels, and those with hypertension.In the future, the need for enhanced MCI screening for CMM patients should be strengthened, and targeted prevention and control of cognitive impairment should be implemented for high-risk populations.

Objective To study the effect of hearing loss on language function and the mediating effect of de-pression on hearing loss and language function,to provide a reference for the intervention of language function im-pairment in the elderly.Methods Data of 6 002 older adults ≥65 years old from the Hubei Aging and Memory Co-hort Study(HAMCS)were collected from 2018 to 2022.A multivariate logistic regression model was used to ana-lyze the effect of hearing loss on language function,and a Bootstrap method was used to analyze the mediating effect of depression score on hearing loss on language function.Results Among 6 002 older adults ≥65 years old,1 137(18.94％)had mild hearing loss,264(4.40％)had moderate and severe hearing loss,and 2 611(43.50％)had language function impairment.After controlling for related factors such as age,years of education,marital status,place of residence,physical exercise,intellectual activity,hypertension,coronary heart disease and cerebrovascular disease,multivariate logistic regression analysis showed that the risk of speech function impairment in the elderly with mild hearing loss and moderate to severe hearing loss was 1.33 times(95％CI:1.13～1.56,P=0.001)and 1.77 times(95％CI:1.29～2.42,P＜0.001)respectively.The mediating effect showed that depression played a partial mediating role between hearing loss and language function,and the mediating effect was-0.021(95％CI:-0.027～-0.015,P＜0.001),accounting for 12.96％of the total effects.Conclusion Hearing loss increases the risk of language impairment,and depression playing a partial mediating role between hearing loss and language func-tion in the elderly.

Objective: To explore the therapeutic effects of ginseng total saponins (GTSs) on cognitive impairments in astronauts caused by prolonged exposure to microgravity environment. Methods: Fifty specific pathogen-free (SPF) male Wistar rats were randomized into control, hindlimb suspension (HLS), Huperzine A (HLS-Hup A 0.1 mg/kg), low-dose GTSs (HLS-GTSs 100 mg/kg), and high-dose GTSs (HLS-GTSs 200 mg/kg) groups, based on the completion time of reward-directed conditioning tasks. Except for rats in the control group, the others were subjected to HLS and treated with drugs (day 20 – 58), received reflex test under the condition of rewarding, and underwent Nissl body staining and Western blot detection on hippocampal. Results: After modeling, rats in HLS group exhibited a reduction in the number of lever presses and an increase in the completion time of the reward-directed operant conditioning task Ⅰ (P < 0.05) when compared with the control group, which were not substantially altered in the HLS-GTSs 100 and 200 mg/kg groups (P > 0.05). In the reward-directed operant conditioning task Ⅱ, the HLS group rats demonstrated a marked decrease in the number of lever presses (P < 0.05) and nose pokes (P < 0.01) when compared with the control group rats; the HLS-GTSs 100 mg/kg showed a significant increase in the number of lever presses and nose pokes (P < 0.05), while the HLS-GTSs 200 mg/kg demonstrated a significant reduction in completion time and an elevation in the number of lever presses (P < 0.05) when compared with the HLS group rats. In visual signal discrimination task, compared with the control group rats, the HLS group rats showed decrease in the indexes of the visual signal discrimination(P < 0.01), while HLS-GTSs 100 and 200 mg/kg groups exhibited manifest increase in it (P < 0.01). In reward extinction experiment, the number of lever presses in HLS rats significantly increased when compared with the control group (P < 0.01); compared with the HLS group, HLS-GTSs 100 and 200 mg/kg groups demonstrated a marked descrease (P < 0.05). The expressions of N-methyl-D-aspartic acid receptor 1 (NR1) and phosophorylated N-methyl-Daspartic acid receptor 2B (p-NR2B) proteins were markedly decreased in rats in the HLS group (P < 0.05 and P < 0.01, respectively), while that of NR2B protein maintained the same (P > 0.05). GTSs increased the expression levels of p-NR2B (P < 0.01). Conclusion GTSs improved the learning and memory ability of complex operations by regulating the NR1/NR2B phosphorylation pathways in rats.