BACKGROUND:Alzheimer's disease has been associated with sarcopenia,but a causal relationship has not been established.Exploring the causal relationship between the two most common disability-burdening diseases in the aging population-Alzheimer's disease and sarcopenia-and their potential mediating factors holds certain implications for further alleviating the healthcare costs and socioeconomic burden for older adults in China.OBJECTIVE:To explore the potential causal relationship between Alzheimer's disease and sarcopenia in the general population using a Mendelian randomization study and to explore the role of body mass index in this context.METHODS:Two-sample Mendelian randomization analysis based on published genome-wide association studies(GWAS)were used to infer causality,and univariate Mendelian randomization and mediation analyses were used in the study design.Through the Integrative Epidemiology Unit(IEU)database,ieu-b-2 was selected as the Alzheimer's disease dataset(sample size:63 926),ieu-b-4816 as the body mass index dataset(99 998),ebi-a-GCST90000027 as the appendicular lean mass dataset(244 730),ukb-b-7478 as the left hand grip strength dataset(461 026),ukb-b-10215 as the right hand grip strength dataset(461 089)and ukb-b-4711 as the walking pace dataset(459 915).Inverse-variance weighting was used as the primary analysis method,and the results were validated by pleiotropy and heterogeneity analysis.The Steiger Directionality Test was performed to validate the reasonableness of the causal direction.RESULTS AND CONCLUSION:(1)The Mendelian randomization analyses provided evidence that Alzheimer's disease predicted the risk of appendicular lean mass[odds ratio(OR)=1.009;95％confidence interval(Cl),1.001-1.017;P=0.023),and walking pace(OR=1.010;95％Cl,1.003-1.017;P=0.008).No correlation with hand grip strength was observed.(2)Alzheimer's disease was negatively correlated with body mass index(OR=0.893;95％Cl,0.811-0.984;P=0.022);body mass index was positively correlated with appendicular lean mass(OR=1.084;95％Cl,1.031-1.141;P=0.002)and negatively correlated with walking pace(OR=0.975;95％Cl,0.969-0.980;P＜0.001).(3)Mediation analyses showed that the causal relationship between Alzheimer's disease and appendicular lean mass and walking pace was partially mediated by body mass index,with the proportion of mediations being 50.25％and 32.11％,respectively.(4)The results of this study suggest that based on large-scale population studies,genetic prediction of Alzheimer's disease is a potential risk factor for sarcopenia,in which body mass index plays an important mediating role.This suggests that in clinical practice,attention should be paid to the muscle condition of patients with Alzheimer's disease,and weight management should be implemented,as maintaining a body mass index within the normal high range may have a preventive effect on the occurrence of sarcopenia in patients with Alzheimer's disease.However,further research is needed to verify the applicability of this conclusion to other ethnic groups.This study utilized an international public database for analysis,providing a reference for research on the correlation between Alzheimer's disease and sarcopenia in the Chinese population.It also highlights the significant mediating role of body mass index,offering insights for further prevention and treatment of sarcopenia among Chinese individuals.

BACKGROUND:Alzheimer's disease has been associated with sarcopenia,but a causal relationship has not been established.Exploring the causal relationship between the two most common disability-burdening diseases in the aging population-Alzheimer's disease and sarcopenia-and their potential mediating factors holds certain implications for further alleviating the healthcare costs and socioeconomic burden for older adults in China.OBJECTIVE:To explore the potential causal relationship between Alzheimer's disease and sarcopenia in the general population using a Mendelian randomization study and to explore the role of body mass index in this context.METHODS:Two-sample Mendelian randomization analysis based on published genome-wide association studies(GWAS)were used to infer causality,and univariate Mendelian randomization and mediation analyses were used in the study design.Through the Integrative Epidemiology Unit(IEU)database,ieu-b-2 was selected as the Alzheimer's disease dataset(sample size:63 926),ieu-b-4816 as the body mass index dataset(99 998),ebi-a-GCST90000027 as the appendicular lean mass dataset(244 730),ukb-b-7478 as the left hand grip strength dataset(461 026),ukb-b-10215 as the right hand grip strength dataset(461 089)and ukb-b-4711 as the walking pace dataset(459 915).Inverse-variance weighting was used as the primary analysis method,and the results were validated by pleiotropy and heterogeneity analysis.The Steiger Directionality Test was performed to validate the reasonableness of the causal direction.RESULTS AND CONCLUSION:(1)The Mendelian randomization analyses provided evidence that Alzheimer's disease predicted the risk of appendicular lean mass[odds ratio(OR)=1.009;95％confidence interval(Cl),1.001-1.017;P=0.023),and walking pace(OR=1.010;95％Cl,1.003-1.017;P=0.008).No correlation with hand grip strength was observed.(2)Alzheimer's disease was negatively correlated with body mass index(OR=0.893;95％Cl,0.811-0.984;P=0.022);body mass index was positively correlated with appendicular lean mass(OR=1.084;95％Cl,1.031-1.141;P=0.002)and negatively correlated with walking pace(OR=0.975;95％Cl,0.969-0.980;P＜0.001).(3)Mediation analyses showed that the causal relationship between Alzheimer's disease and appendicular lean mass and walking pace was partially mediated by body mass index,with the proportion of mediations being 50.25％and 32.11％,respectively.(4)The results of this study suggest that based on large-scale population studies,genetic prediction of Alzheimer's disease is a potential risk factor for sarcopenia,in which body mass index plays an important mediating role.This suggests that in clinical practice,attention should be paid to the muscle condition of patients with Alzheimer's disease,and weight management should be implemented,as maintaining a body mass index within the normal high range may have a preventive effect on the occurrence of sarcopenia in patients with Alzheimer's disease.However,further research is needed to verify the applicability of this conclusion to other ethnic groups.This study utilized an international public database for analysis,providing a reference for research on the correlation between Alzheimer's disease and sarcopenia in the Chinese population.It also highlights the significant mediating role of body mass index,offering insights for further prevention and treatment of sarcopenia among Chinese individuals.

Objective:To evaluate the efficacy and safety of oral semaglutide versus sitagliptin in Chinese patients with type 2 diabetes mellitus(T2DM) inadequately controlled with metformin. Methods:The PIONEER 12 study was a phase Ⅲ clinical trial. Chinese patients were prospectively randomized to oral semaglutide(3mg, 7 mg, and 14 mg) or sitagliptin 100 mg. The primary endpoint was the change in HbA 1C from baseline to week 26, and the confirmatory secondary efficacy endpoint was the change in body weight from baseline to week 26. Results:Totally 1 084 Chinese participants(mean age 53 years, male 62.2%, mean duration of diabetes 5.5 years, HbA 1C 8.2%, and body weight 74.3 kg) were enrolled. The changes in HbA 1C at week 26 from baseline were -0.9%, -1.4%, and -1.6% for oral semaglutide 3 mg, 7 mg, and 14 mg, respectively, and -0.7% for sitagliptin. Compared to sitagliptin, oral semaglutide 3 mg, 7 mg, and 14 mg significantly reduced HbA 1C [estimated treatment difference(ETD), -0.2%(95% CI -0.4--0.0), -0.8%(95% CI -0.9--0.6), and -0.9%(95% CI -1.1--0.8), respectively; 3 mg, P=0.011, 7 mg and 14mg, P<0.001]. The estimated mean changes in body weight at week 26 from baseline were -1.1 kg, -2.5 kg, and -3.4 kg for oral semaglutide 3 mg, 7 mg, and 14 mg, respectively, and -0.4 kg for sitagliptin 100 mg. Compared with sitagliptin, oral semaglutide 3 mg, 7 mg, and 14 mg significantly reduced body weight [ETD, -0.8 kg(95% CI -1.3--0.2), -2.1 kg(95% CI -2.6--1.6), and -3.0 kg(95% CI -3.5--2.5), respectively; 3 mg, P=0.004, 7 mg and 14 mg, P<0.001]. The overall incidence of adverse events was similar across all treatment groups. The most common adverse events were gastrointestinal disorders, mostly mild or moderate in severity and transient in duration. Conclusions:Oral semaglutide resulted in significantly greater reduction in HbA 1C and body weight versus sitagliptin at week 26, with a favorable safety and tolerability profile in Chinese T2DM patients inadequately controlled with metformin.

Humans ; Hydrocarbons, Brominated ; toxicity ; Occupational Exposure ; standards

OBJECTIVETo study the effects of 1-bromopropane (1-BP) on liver and kidney functions of exposed workers.

METHODSOccupational health situation in three 1-BP plants was investigated. Fifty-four workers from the 1-BP manufacturing line were chose to be contact group, while 42 workers from non-1-BP manufacturing line as control group. All workers underwent questionnaire survey, liver function test as well as kidney function test.

RESULTWorking years has no impact on liver and kidney functions of workers from contact group. Compared with the control, liver and kidney functions test of the two groups showed no statistical difference either.

CONCLUSIONThe present investigation doesn't prove any impact of occupational 1-BP exposure on worker's liver and kidney functions.

Humans ; Hydrocarbons, Brominated ; toxicity ; Kidney ; drug effects ; Liver ; drug effects ; Occupational Exposure ; adverse effects

OBJECTIVETo investigate the clinical features of familial papillary thyroid carcinoma (FPTC) and the criteria for its diagnosis and surgical treatment.

METHODSOne hundred and forty-five patients with PTC were investigated randomly between January 1999 and November 2001, and 17 of them were from 7 families. Of the 17 patients, 14 were operated on at this hospital, and 3 were operated elsewhere. The specimens from the 17 patients were confirmed pathologically. They accounted for 9.3% (14/145) of all PTC patients.

RESULTSThe patients were aged from 30 to 74 years (mean 45 years). The diameter of original focuses ranged from 0.8 to 2.8 cm (mean diameter 1.7 cm). Of the 17 patients with PTC, 8 (47.5%) had bilateral carcinoma. In 3 families, 3 patients suffered from PTC (42.8%). In 4 families, other members suffered from benign thyroid tumor or non-tumorous thyroid disease. Among the 17 patients, 10 had nodular goiters. Thyroidectomy, unilateral thyroidectomy plus isthmusectomy, and combined radical operation were performed in 8, 9, 14 patients, respectively. Early metastatic spread to local regional lymph nodes was noted in 14 patients (82.3% or 14/17).

CONCLUSIONSIn this study, a FPTC rate of 10% was found. Almost 50% of FPTC patients had bilateral carcinoma. The frequency of metastatic spread to local-regional lymph nodes was high. Follow-up survey of family members should be performed in a long period of time.

Adult ; Aged ; Carcinoma, Papillary ; genetics ; pathology ; surgery ; Female ; Humans ; Lymphatic Metastasis ; Male ; Middle Aged ; Thyroid Neoplasms ; genetics ; pathology ; surgery ; Thyroidectomy