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.

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 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.

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.

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.

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 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 study the characteristics of a rat model of migraine with hyperactivity of liver-yang and blood stagnation,which was established by Fuzi Decoction combined with electrical stimulation of the trigeminal ganglion.Methods The 30 SD rats were divided into normal group,model group,and Zhengtian pill group(1.6 g·kg-1),with 10 rats in each group.Rats in the model group and Zhengtian pill group were fed with aconite decoction(2.00 g·kg-1)once a day for 28 day to establish the hyperthermia model;On the 15 day of intragastric administration,rats in the Zhengtai pill group were simultaneously given Zhengtai pill solution once a day for 14 day;At 29 day,the trigeminal ganglion was stimulated to create the migraine model of hyperliver and stasis.After 30 min of the last dose,the macroscopic signs and behaviors were observed,and the blood rheology was detected by blood visticometer.Positive substance P(SP)expression,mRNA and relative protein expression in the trigeminal cervical pulp complex(TCC)in rat mice by immunohistochemistry,RT-qPCR and Western blot analysis.Results Compared with the normal group,the model group has macro signs such as red eyes,irritability,cage fighting,dark tongue and stasis points;regular head positioning and frequent hair management;increased distance in the central area(P<0.05).The relative viscosity of whole blood,plasma viscosity,red blood cell aggregation index all increased(P<0.05),and the red blood cell variant index decreased(P<0.05);SP positive expression,mRNA and the relative protein expression increased in TCC(P<0.05).Compared with model group,Zhengtian pill group can improve macro representation and behavior significantly;can significantly reduce central distance(P<0.05);can reduce plasma viscosity,high-shear relative viscosity of whole blood,and red blood cell aggregation index(P<0.05);increase the Red blood cell variant index significantly(P<0.05);down-regulate SP positive expression,mRNA and relative protein expression in TCC(P<0.05,P<0.01).Conclusion SD rats were used for 4 weeks to construct a migraine model of hyperhepatic hyperactivity and stasis,which was basically consistent with the clinical manifestations.