Objective To investigate the molecular mechanism of aprepitant(Apr)reversing 5-Fluorouracil(5-FU)resistance in colorectal cancer(CRC)mouse model through endoplasmic re-ticulum stress(ERS).Methods Thirty mice were selected as experimental animals.Five mice were randomly assigned to control group,and the remaining 25 mice underwent subcutaneous injection in the back to establish the HCT-116/5-FU CRC mouse model.These mice were then divided into the CRC group,5-FU group,Apr group,Apr+5-FU group and Apr+ERS inhibitor Tauroursodeoxychol-ic acid(TUDCA)group,with five mice in each group.Changes in body weight and tumorigenesis in mice were recorded,and their organ indicators were calculated.Western blotting(WB)was used to detect the protein expression levels of protein kinase R-like ER kinase(PERK),eukaryotic initiation factor 2 subunit α(eIF2α),activating transcription factor 4(ATF4)and C/EBP homologous protein(CHOP)in each group.Results At 5,10,15 and 20 d after medication,there were no statistically significant differences in body weight among CRC,5-FU,Apr,Apr+5-FU and Apr+TUDCA groups,neither in time points nor in interactions(P＞0.05).Two days after the last administration,there was no significant difference in the indexes of thymus,lung,liver,spleen,heart,kidney and other organs among all groups(P＞0.05).Compared with CRC group,the protein expression levels of PERK,P-EIF2α/eIF2α,ATF4 and CHOP in Apr group and Apr+5-FU group were significantly increased,the number of tumors was significantly decreased,the tumor mass was significantly de-creased,and the tumor volume was significantly decreased(P＜0.05),and the improvement of Apr+5-FU group was better than that of other groups(P＜0.05).Conclusion Apr can enhance chemotherapy sensitivity and reverse chemotherapy resistance in CRC mice,which may be mediated by downstream molecules of ERS pathway.

Objective:To analyze the comorbidity patterns between thyroid dysfunction and other common cardiometabolic diseases.Methods:In this cross-sectional study, 93 967 participants aged 18 years or older who underwent thyroid function tests at the Health Checkup Center of China-Japan Friendship Hospital between 2017 and 2024 were included. The comorbidity patterns between thyroid dysfunction and six common cardiometabolic diseases of obesity, diabetes, hypertension, dyslipidemia, hyperuricemia, and non-alcoholic fatty liver disease (NAFLD) were described systematicly. The logistic regression models was used to analyze the association between thyroid dysfunction and these cardiometabolic diseases.Results:The detection rates of subclinical hyperthyroidism, overt hyperthyroidism, subclinical hypothyroidism, and overt hypothyroidism in those participants was 1.9%, 0.9%, 3.7% and 1.1%, respectively. The proportion of the paticipants with subclinical hyperthyroidism, overt hyperthyroidism, subclinical hypothyroidism, and overt hypothyroidism who had at least one comorbid cardiometabolic disease was 67.5%, 64.8%, 73.5%, and 77.6%, respectively; the proportion of those participants with two or more concurrent cardiometabolic diseases was 38.6%, 36.7%, 42.8%, and 47.5%, respectively; and the proportion with three or more concurrent cardiometabolic diseases was 19.0%, 18.1%, 22.9%, and 27.5%, respectively. After adjusting for age and gender, the participants with overt hypothyroidism (≥2 comorbidities: OR=1.7, 95% CI: 1.5-1.9;≥3 comorbidities: OR=1.8, 95% CI: 1.5-2.1) or subclinical hypothyroidism (≥2 comorbidities: OR=1.3, 95% CI: 1.2-1.4;≥3 comorbidities: OR=1.3, 95% CI: 1.2-1.4) had a significantly higher risk of multiple cardiometabolic diseases when compared with euthyroid individuals. Analysis of comorbidity patterns revealed that individuals with overt hyperthyroidism ( OR=1.8, 95% CI: 1.0-3.1) and subclinical hyperthyroidism ( OR=1.5, 95% CI=1.0-2.2) had a significantly higher risk of the “NAFLD+hypertension” comorbidity complex when compared with euthyroid individuals. Similarly, individuals with overt hypothyroidism ( OR=1.7, 95% CI: 1.2-2.3) and subclinical hypothyroidism ( OR=1.3, 95% CI: 1.1-1.5) had a significantly higher risk of the “dyslipidemia+NAFLD+hyperuricemia” comorbidity complex when compared with euthyroid individuals. Conclusion:Individuals with thyroid dysfunction exhibit a high prevalence of comorbid cardiometabolic diseases, highlighting the need for future research on integrated management strategies for multimorbidity in this population.

Objective:To analyze the comorbidity patterns between thyroid dysfunction and other common cardiometabolic diseases.Methods:In this cross-sectional study, 93 967 participants aged 18 years or older who underwent thyroid function tests at the Health Checkup Center of China-Japan Friendship Hospital between 2017 and 2024 were included. The comorbidity patterns between thyroid dysfunction and six common cardiometabolic diseases of obesity, diabetes, hypertension, dyslipidemia, hyperuricemia, and non-alcoholic fatty liver disease (NAFLD) were described systematicly. The logistic regression models was used to analyze the association between thyroid dysfunction and these cardiometabolic diseases.Results:The detection rates of subclinical hyperthyroidism, overt hyperthyroidism, subclinical hypothyroidism, and overt hypothyroidism in those participants was 1.9%, 0.9%, 3.7% and 1.1%, respectively. The proportion of the paticipants with subclinical hyperthyroidism, overt hyperthyroidism, subclinical hypothyroidism, and overt hypothyroidism who had at least one comorbid cardiometabolic disease was 67.5%, 64.8%, 73.5%, and 77.6%, respectively; the proportion of those participants with two or more concurrent cardiometabolic diseases was 38.6%, 36.7%, 42.8%, and 47.5%, respectively; and the proportion with three or more concurrent cardiometabolic diseases was 19.0%, 18.1%, 22.9%, and 27.5%, respectively. After adjusting for age and gender, the participants with overt hypothyroidism (≥2 comorbidities: OR=1.7, 95% CI: 1.5-1.9;≥3 comorbidities: OR=1.8, 95% CI: 1.5-2.1) or subclinical hypothyroidism (≥2 comorbidities: OR=1.3, 95% CI: 1.2-1.4;≥3 comorbidities: OR=1.3, 95% CI: 1.2-1.4) had a significantly higher risk of multiple cardiometabolic diseases when compared with euthyroid individuals. Analysis of comorbidity patterns revealed that individuals with overt hyperthyroidism ( OR=1.8, 95% CI: 1.0-3.1) and subclinical hyperthyroidism ( OR=1.5, 95% CI=1.0-2.2) had a significantly higher risk of the “NAFLD+hypertension” comorbidity complex when compared with euthyroid individuals. Similarly, individuals with overt hypothyroidism ( OR=1.7, 95% CI: 1.2-2.3) and subclinical hypothyroidism ( OR=1.3, 95% CI: 1.1-1.5) had a significantly higher risk of the “dyslipidemia+NAFLD+hyperuricemia” comorbidity complex when compared with euthyroid individuals. Conclusion:Individuals with thyroid dysfunction exhibit a high prevalence of comorbid cardiometabolic diseases, highlighting the need for future research on integrated management strategies for multimorbidity in this population.