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 investigate effect of cassava RS3 resistant starch(Ce-RS3)on serum homocysteine(Hcy)level in patients with atherosclerotic cerebral infarction(ACI)during the recovery period.Methods A total of 55 patients with ACI at the First Affiliated Hospital of Guizhou University of Traditional Chinese Medicine from October 2023 to October 2024 were selected as subjects.They were devieded into observation group(n=28)and control group(n=27)using a random number table.The control group received atorvastatin calcium,phospholipids,and aspirin,while the observation group received atorvastatin calcium,phospholipids,aspirin,and Ce-RS3.After 12 weeks of treatment,homocysteine(Hcy)levels,carotid plaque diameter,National Institutes of Health stroke scale(NIHSS)scores,Barthel index(BI)scores,and traditional Chinese medicine(TCM)syndrome scores were compared between two groups.Results After treatment,the serum Hcy levels decreased and carotid plaque size reduced in both groups,with the NIHSS scores and TCM syndrome scores also decreased,and observation group was lower than control group(P＜0.05).After treatment,the BI score increased,with observation group higher than control group(P＜0.05).Conclusion The use of Ce-RS3 in the recovery phase of patients with ACI can effectively improve neurological function and enhance treatment efficacy.

Objective:To investigate the effects of Vibrio vulnificus ( Vv) quorum-sensing protein LuxS on the homeostasis of pulmonary innate immune cells in sepsis-induced acute lung injury. Methods:This study constructed luxS knockout and complemented Vv strains. The time required for wild type, luxS knockout, and complemented Vv strains to grow to an absorbance of 600 nm in liquid medium was measured using a spectrophotometer. Iron-overloaded mice were intraperitoneally infected with 1×10 5 CFU of the above three kinds of Vv strains, respectively. Clinical scoring for sepsis-induced dyspnea was used to evaluate the respiratory quality in mice. At 7 h after infection, the pathological changes in lung tissues were observed by HE staining; the bacterial loads in lung tissues were measured; the single-cell suspension of lung tissues was analyzed by flow cytometry. Uniform manifold approximation and projection (UMAP) was used to reduce the dimension of the distribution of CD45 + immune cells in lung tissues of mice in the PBS control group and infection groups with different strains. The frequency and absolute number of innate immune cells in lung tissues were analyzed by multicolor flow cytometry. One-way analysis of variance and t test were used for statistical analysis. Results:There was no significant difference in the growth rate of wild type, luxS knockout, and complemented Vv strains in liquid medium. Compared with the mice infected with the wild type or complemented strain, the mice infected with the luxS knockout strain exhibited overall alleviated respiratory difficulty, decreased inflammatory cell infiltration in lung tissues, and reduced bacterial load in lung tissues ( P<0.05). Besides, there was no significant difference in clinical respiratory scores, inflammatory cell infiltration, or bacterial loads between the mice infected with the complemented strain and wild type strain. UMAP analysis showed that compared with the mice infected with the luxS knockout strain, the mice infected with the wild type or complemented strain showed increased proportions of neutrophils and eosinophils in lung tissues. Results of multicolor flow cytometry analysis further verified that the proportions of neutrophils and eosinophils were significantly lower in the mice infected with the luxS knockout strain than in the mice infected with wild type or complemented strain ( P<0.01, P<0.000 1), while the proportion of alveolar macrophages was significantly higher as compared with that in the mice infected with wild type or complemented strain ( P<0.01). Conclusion:During Vv infection, LuxS may promote acute lung injury by affecting the homeostasis of neutrophils, eosinophils and resident macrophages in lung tissues.

Objective:To investigate the role of autophagy in the regulatory of phagocytosis in Vibrio vulnificus ( V. vulnificus)-infected murine macrophages. Methods:The expression of cellular autophagy-related proteins in PBS-treated and V. vulnificus-infected RAW264.7 and BMMφ cells was detected by Western blot. The co-localization of V. vulnificus-GFP and LC3Ⅱ protein in V. vulnificus-GFP-infected RAW264.7 and BMMφ cells were detected using confocal microscopy. The phagocytosis of V. vulnificus in V. vulnificus-GFP-infected RAW264.7 and BMMφ cells with or without autophagy inhibition using Bafilomycin A1 was detected by flow cytometry. Results:The up-regulated levels of Atg7, Atg12 and Atg16L1 proteins, increased LC3Ⅱ/actin ratio, as well as down-regulated p62 protein levels were significantly detected in V. vulnificus-infected RAW264.7 and BMMφ cells. The co-localization of V. vulnificus-GFP and LC3Ⅱ protein was clearly observed in V. vulnificus-GFP-infected RAW264.7 and BMMφ cells. Enhanced phagocytosis of V. vulnificus and increased autophagy were exhibited in V. vulnificus-GFP-infected RAW264.7 and BMMφ cells, while weakened phagocytosis, accumulation of Atg7, Atg12, Atg16L1, LC3Ⅱ and p62 protein levels, as well as blocking autophagy flux were detected in those cells within autophagy inhibition using Bafilomycin A1. Conclusion:Autophagy induced by V. vulnificus infection could promote phagocytosis of V. vulnificus in macrophages.

Objective To investigate effect of cassava RS3 resistant starch(Ce-RS3)on serum homocysteine(Hcy)level in patients with atherosclerotic cerebral infarction(ACI)during the recovery period.Methods A total of 55 patients with ACI at the First Affiliated Hospital of Guizhou University of Traditional Chinese Medicine from October 2023 to October 2024 were selected as subjects.They were devieded into observation group(n=28)and control group(n=27)using a random number table.The control group received atorvastatin calcium,phospholipids,and aspirin,while the observation group received atorvastatin calcium,phospholipids,aspirin,and Ce-RS3.After 12 weeks of treatment,homocysteine(Hcy)levels,carotid plaque diameter,National Institutes of Health stroke scale(NIHSS)scores,Barthel index(BI)scores,and traditional Chinese medicine(TCM)syndrome scores were compared between two groups.Results After treatment,the serum Hcy levels decreased and carotid plaque size reduced in both groups,with the NIHSS scores and TCM syndrome scores also decreased,and observation group was lower than control group(P＜0.05).After treatment,the BI score increased,with observation group higher than control group(P＜0.05).Conclusion The use of Ce-RS3 in the recovery phase of patients with ACI can effectively improve neurological function and enhance treatment efficacy.

Objective:To investigate the effects of Vibrio vulnificus ( Vv) quorum-sensing protein LuxS on the homeostasis of pulmonary innate immune cells in sepsis-induced acute lung injury. Methods:This study constructed luxS knockout and complemented Vv strains. The time required for wild type, luxS knockout, and complemented Vv strains to grow to an absorbance of 600 nm in liquid medium was measured using a spectrophotometer. Iron-overloaded mice were intraperitoneally infected with 1×10 5 CFU of the above three kinds of Vv strains, respectively. Clinical scoring for sepsis-induced dyspnea was used to evaluate the respiratory quality in mice. At 7 h after infection, the pathological changes in lung tissues were observed by HE staining; the bacterial loads in lung tissues were measured; the single-cell suspension of lung tissues was analyzed by flow cytometry. Uniform manifold approximation and projection (UMAP) was used to reduce the dimension of the distribution of CD45 + immune cells in lung tissues of mice in the PBS control group and infection groups with different strains. The frequency and absolute number of innate immune cells in lung tissues were analyzed by multicolor flow cytometry. One-way analysis of variance and t test were used for statistical analysis. Results:There was no significant difference in the growth rate of wild type, luxS knockout, and complemented Vv strains in liquid medium. Compared with the mice infected with the wild type or complemented strain, the mice infected with the luxS knockout strain exhibited overall alleviated respiratory difficulty, decreased inflammatory cell infiltration in lung tissues, and reduced bacterial load in lung tissues ( P<0.05). Besides, there was no significant difference in clinical respiratory scores, inflammatory cell infiltration, or bacterial loads between the mice infected with the complemented strain and wild type strain. UMAP analysis showed that compared with the mice infected with the luxS knockout strain, the mice infected with the wild type or complemented strain showed increased proportions of neutrophils and eosinophils in lung tissues. Results of multicolor flow cytometry analysis further verified that the proportions of neutrophils and eosinophils were significantly lower in the mice infected with the luxS knockout strain than in the mice infected with wild type or complemented strain ( P<0.01, P<0.000 1), while the proportion of alveolar macrophages was significantly higher as compared with that in the mice infected with wild type or complemented strain ( P<0.01). Conclusion:During Vv infection, LuxS may promote acute lung injury by affecting the homeostasis of neutrophils, eosinophils and resident macrophages in lung tissues.

Objective:To investigate the role of autophagy in the regulatory of phagocytosis in Vibrio vulnificus ( V. vulnificus)-infected murine macrophages. Methods:The expression of cellular autophagy-related proteins in PBS-treated and V. vulnificus-infected RAW264.7 and BMMφ cells was detected by Western blot. The co-localization of V. vulnificus-GFP and LC3Ⅱ protein in V. vulnificus-GFP-infected RAW264.7 and BMMφ cells were detected using confocal microscopy. The phagocytosis of V. vulnificus in V. vulnificus-GFP-infected RAW264.7 and BMMφ cells with or without autophagy inhibition using Bafilomycin A1 was detected by flow cytometry. Results:The up-regulated levels of Atg7, Atg12 and Atg16L1 proteins, increased LC3Ⅱ/actin ratio, as well as down-regulated p62 protein levels were significantly detected in V. vulnificus-infected RAW264.7 and BMMφ cells. The co-localization of V. vulnificus-GFP and LC3Ⅱ protein was clearly observed in V. vulnificus-GFP-infected RAW264.7 and BMMφ cells. Enhanced phagocytosis of V. vulnificus and increased autophagy were exhibited in V. vulnificus-GFP-infected RAW264.7 and BMMφ cells, while weakened phagocytosis, accumulation of Atg7, Atg12, Atg16L1, LC3Ⅱ and p62 protein levels, as well as blocking autophagy flux were detected in those cells within autophagy inhibition using Bafilomycin A1. Conclusion:Autophagy induced by V. vulnificus infection could promote phagocytosis of V. vulnificus in macrophages.

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.

This study aims to analyze the differentiating factors between only allergic rhinitis and allergic rhinitis combined with other allergic diseases in pre-school children and to explore the impact of relevant family and maternal factors during pregnancy on pediatric allergic diseases.The study employed an epidemiological cross-sectional survey design, conducted from January to June 2022 at the Helong Street Health Service Center in Baiyun District, Guangzhou City, China. This cross-sectional investigation focused on 15 preschool education centers within the jurisdiction. It encompassed a total of 4 661 pre-school children aged 3-6 years within the district, resulting in the collection of 3 437 valid questionnaires. The study utilized an online survey, covering aspects such as children′s birth conditions, early living environment, maternal lifestyle and emotional state during pregnancy, and paternal information. The questionnaire was designed by an expert team and incorporated advanced logic functions to ensure data accuracy. Diagnosis of allergic diseases included evaluation of symptoms such as rhinitis, asthma, eczema and along with collecting family member′s allergy information. Factors like maternal emotional stress during pregnancy, premature birth, and breastfeeding were also considered. The analysis of frequency differences between groups was conducted using the Chi-square test. The distribution differences between two groups were examined using the t-test or Mann-Whitney U test. Additionally, binary logistic regression analysis was employed to identify risk factors for the occurrence of allergic diseases. To illustrate the distribution and co-occurrence of different allergic diseases in children, upset plots were created. Furthermore, forest plots were utilized to analyze the risk factors. The study included 455 children with only allergic rhinitis and 759 children with rhinitis combined with other allergic diseases. The results showed no significant demographic differences between the two groups. Logistic model results indicated that children with allergic rhinitis who had suffered from severe eczema within the first 12 months had a OR(95% CI):19.818 times (2.670-147.095) higher probability of developing combined allergic diseases than those without eczema, while the probability increased 2.345 times (1.825-3.013) for those with mild to moderate eczema. A higher level of maternal education was also identified as a risk factor, increasing the risk by about 1.5 times. Additionally, the risk of developing combined allergic diseases in children with one allergic parent was OR(95% CI):1.662 times (1.273-2.170) higher than in those with non-allergic parents, and 2.181 times (1.504-3.163) higher if both parents had allergies. Moreover, negative maternal emotional stress during pregnancy was more significant in children with combined allergic diseases. In conclusion, severe eczema in the first 12 months, mild to moderate eczema; allergies in one or both parents; parents′ educational level, household disposable income level; firstborn status; and negative maternal emotions during pregnancy are risk factors for children with allergic rhinitis combined with other allergic diseases.