BACKGROUND:Gut microbiota is closely related to host energy balance and metabolism.The metabolites of intestinal flora can regulate the occurrence and development of obesity and can be a new target for the prevention and treatment of obesity. OBJECTIVE:To summarize the interaction between the intestinal flora and obesity,as well as the specific mechanism underlying regulation of obesity by metabolites of intestinal flora,thereby providing a new reference and basis for the prevention and treatment of obesity. METHODS:"Intestinal microbiota,intestinal bacteria,intestinal microbiota metabolites,short-chain fatty acids,bile acids,ipopolysaccharide,trimethylamine N-oxide,medium-chain fatty acids,tryptophan derivatives,obesity"were used as search terms in Chinese and English.Literature related to obesity from 1990 to 2022 was retrieved in PubMed and CNKI databases.According to inclusion and exclusion criteria,88 articles were finally selected. RESULTS AND CONCLUSION:Intestinal flora is closely related to the occurrence and development of obesity.For example,changes in the Firmicutes to Bacteroidetes ratio can be used as a biomarker for the diagnosis of obesity,and the occurrence of obesity can be delayed by the colonization of probiotics such as Bifidobacterium breve,Lactobacillus and Akkermansia.Intestinal flora is mainly mediated by the metabolites of intestinal flora to participate in the regulation of obesity.For example,short-chain fatty acid can regulate adipogenesis by regulating signaling pathways such as G protein-coupled receptors 41,43 and peroxisome proliferator-activated receptor γ,thus delaying the occurrence and development of obesity.Bile acids can increase insulin sensitivity and body energy expenditure by promoting the activation of G protein-coupled receptor 5 and farnesol X receptor.In addition,lipopolysaccharide,trimethylamine oxide,medium-chain fatty acids and tryptophan derivatives are also widely involved in the occurrence and development of obesity through various signaling pathways.Further studies have found that metabolites of the same bacterial community exert heterogeneous effects in the specific process of regulating obesity via different signaling pathways.For example,under the influence of high-fat diet,acetic acids can activate the parasympathetic nervous system,leading to hyperphagia and liver insulin resistance and thus accelerating the physiological course of obesity.

BACKGROUND:Intestinal flora and its metabolites can participate in the pathological process of osteoporosis and play an important role in the diagnosis and treatment of osteoporosis.In addition,exercise can regulate the intestinal flora and thus affect the occurrence and development of osteoporosis. OBJECTIVE:To summarize the effects and mechanism of intestinal flora on osteoblasts,osteoclasts,and bone marrow mesenchymal stem cells,and the potential role of exercise-mediated intestinal flora in regulating osteoporosis. METHODS:"Intestinal flora,intestinal bacteria,metabolites of intestinal flora,bone metabolism,osteoporosis,exercise"were selected as keywords.Literatures from 1990 to 2023 were retrieved from PubMed and CNKI databases. RESULTS AND CONCLUSION:Changes in the abundance and diversity of intestinal flora and changes in the levels of intestinal flora metabolites such as trimethylamine oxide and bile acid can be used as biomarkers for the diagnosis of osteoporosis.The imbalance of intestinal flora can lead to intestinal barrier dysfunction and excessive production of lipopolysaccharides and trimethylamine oxide,induce the secretion of tumor necrosis factor-α and other inflammatory cytokines,activate the nuclear factor κB signaling pathway and aggravate oxidative stress,thus promoting osteoclast differentiation,inducing osteoblast apoptosis and affecting bone marrow mesenchymal cell migration.Remodeling intestinal flora homeostasis can inhibit inflammatory response,downregulate oxidative stress,inhibit osteoclast differentiation,promote osteoblast differentiation,and regulate the osteogenic migration of bone marrow mesenchymal cells to prevent and treat osteoporosis.Exercise can regulate intestinal flora homeostasis,improve intestinal barrier function,promote the secretion of short-chain fatty acids and bile acids,down-regulate serum lipopolysaccharide level,reduce oxidative stress,and then inhibit osteocyte apoptosis,inhibit osteoclast differentiation,promote osteoblast differentiation,and regulate osteocyte nutrient metabolism to exert the potential of preventing and treating osteoporosis.

Objective:This study aims to investigate the anxiety-like behavior induced by cystitis and its neurobio-logical mechanisms in the anterior cingulate cortex(ACC)by constructing a mouse model of cystitis.Methods:A cys-titis model was established using lipopolysaccharide(LPS).Anxiety-like behavior in mice was explored through the open field test,and single-nucleus RNA sequencing was used to analyze changes in gene expression of neurons in the ACC.Results:HE staining results indicated significant inflammatory responses in the bladders of LPS-treated mice,including extensive infiltration of inflammatory cells,tissue edema,and bladder epithelial shedding.The open field test showed that the time and distance of mice moving in the central area of the open field were significantly reduced,indica-ting obvious anxiety-like behavior.Quality control of single-nucleus sequencing data suggested good data quality.Di-mensionality reduction clustering of the top 2000 highly variable genes revealed seven different cell subpopulations in the ACC.Five major cell types were identified in the ACC,and neurons were further clustered into five different subpopula-tions,identifying two main cell types.Differential gene analysis indicated significant changes in gene expression in neu-rons,with functional enrichment in pathways related to synaptic dysfunction.Conclusion:Cystitis can induce changes in gene expression in specific cell subpopulations in the ACC,suggesting that neurons may play an important role in the anxiety-like behavior induced by cystitis.This provides a new perspective for understanding the relationship between cystitis and anxiety behavior and offers important experimental evidence for future exploration of the brain regions and molecular mechanisms underlying cystitis-induced anxiety behavior.

Objective:To investigate the relationship between different obesity metabolic phenotypes and the incidence of new carotid artery plaque.Methods:The present study is a retrospective cohort study, collecting individuals from the Health Management Center of the Second Affiliated Hospital of Dalian Medical University who had two or more cervical vascular color ultrasound examinations and met the inclusion criteria from 2014 to 2022, and collected their baseline clinical data. According to whether the subjects were obese and had metabolic syndrome, they were divided into metabolically healthy non-obese group, metabolically unhealthy non-obese group, metabolically healthy obese group, and metabolically unhealthy obese group. The first physical examination time of the subjects was taken as the starting point of follow-up, and cervical vascular color ultrasound was performed during the follow-up physical examination, with the outcome event being carotid artery plaque. Kaplan-Meier survival curve analysis was used to analyze the cumulative incidence of carotid artery plaques in the four groups and log-rank test was performed, and a multifactorial Cox proportional hazards model was used to analyze the relationship between different obesity metabolic phenotypes and the risk of carotid artery plaque incidence.Results:A total of 4 890 subjects were enrolled, aged (45.4±9.6) years, and 2 754 (56.3%) males. The follow-up time was 1.14(0.93, 2.20) years. Compared with the other 3 obesity metabolic phenotypes, the incidence of carotid plaques in the metabolically unhealthy obesity group was the highest (15.4% (286/1 861)). Kaplan-Meier survival curve analysis showed that the cumulative incidence of carotid plaques in metabolically unhealthy obese subjects was about 2.962 times that of metabolically healthy non-obese subjects (log-rank P<0.001). Multivariate Cox regression results showed that the risk of carotid plaque in metabolically unhealthy obese subjects was 1.650 times that of metabolically healthy non-obese subjects (95% CI: 1.203-2.264, P=0.002). Conclusion:Metabolically unhealthy obesity phenotype is an independent risk factor for carotid plaque.

Objective:The primary goal of this study is to explore the safety and effectiveness of a new modified eversion carotid endarterectomy (MECEA).Methods:This is a retrospective case series study. One hundred patients were consecutively treated with MECEA by the same operator at Department of Vascular Surgery,Peking Union Medical College Hospital from January 2019 to December 2023. There were 77 males and 23 females. The age was (66.0±8.6)years (range: 39 to 85 years). Twenty-four (24.0%) patients were symptomatic with the degree of carotid stenosis over 50%,76 patients (76.0%) were asymptomatic with the degree of stenosis over 70%. All these patients meet the indication of carotid endarterectomy. The main difference between MECEA and traditional eversion carotid endarterectomy was the anterior,lateral,and posterior walls of the internal carotid artery were incised obliquely from the origin of the internal carotid artery toward the common carotid artery,leaving the wall of internal carotid artery intact at the bifurcation. The surgical process,cardiovascular and cerebrovascular complications and other surgical complications were recorded. The incidences of complications,restenosis of intraoperative target lesions and re-intervention were collected during follow-up.Results:All procedures were performed successfully under general anesthesia. The total operation time was (36.5±10.1)minutes (range: 22 to 65 minutes),and carotid clamping time was (15.0±6.3)minutes (range: 7 to 31 minutes). One patient (1.0%) occurred postoperative cerebrovascular accident,1 patient (1.0%) developed cerebral hyperperfusion syndrome (CHS),and another 1 patient (1.0%) suffered myocardial infarction. All these patients were recovered after medical treatment within a week. The follow-up time( M(IQR)) was 24 (28) months (range: 6 to 62 months). Two patients (2.0%) were reported to have hemodynamically significant restenosis within 2 years,with one patient requiring intervention. No patient suffered from ipsilateral ischemic stroke. Conclusions:MECEA is a safe and effective surgical method of treating carotid artery stenosis. This method can reduce carotid clamping time and lowers the risk of ischemic stroke. Meantime,it preserves the integrity of the adventitia at the bifurcation of carotid artery,reduces the chance of restenosis. Moreover,it might be helpful to prevent postoperative CHS due to reducing damage to the carotid body and carotid sinus nerve.

Objective:The primary goal of this study is to explore the safety and effectiveness of a new modified eversion carotid endarterectomy (MECEA).Methods:This is a retrospective case series study. One hundred patients were consecutively treated with MECEA by the same operator at Department of Vascular Surgery,Peking Union Medical College Hospital from January 2019 to December 2023. There were 77 males and 23 females. The age was (66.0±8.6)years (range: 39 to 85 years). Twenty-four (24.0%) patients were symptomatic with the degree of carotid stenosis over 50%,76 patients (76.0%) were asymptomatic with the degree of stenosis over 70%. All these patients meet the indication of carotid endarterectomy. The main difference between MECEA and traditional eversion carotid endarterectomy was the anterior,lateral,and posterior walls of the internal carotid artery were incised obliquely from the origin of the internal carotid artery toward the common carotid artery,leaving the wall of internal carotid artery intact at the bifurcation. The surgical process,cardiovascular and cerebrovascular complications and other surgical complications were recorded. The incidences of complications,restenosis of intraoperative target lesions and re-intervention were collected during follow-up.Results:All procedures were performed successfully under general anesthesia. The total operation time was (36.5±10.1)minutes (range: 22 to 65 minutes),and carotid clamping time was (15.0±6.3)minutes (range: 7 to 31 minutes). One patient (1.0%) occurred postoperative cerebrovascular accident,1 patient (1.0%) developed cerebral hyperperfusion syndrome (CHS),and another 1 patient (1.0%) suffered myocardial infarction. All these patients were recovered after medical treatment within a week. The follow-up time( M(IQR)) was 24 (28) months (range: 6 to 62 months). Two patients (2.0%) were reported to have hemodynamically significant restenosis within 2 years,with one patient requiring intervention. No patient suffered from ipsilateral ischemic stroke. Conclusions:MECEA is a safe and effective surgical method of treating carotid artery stenosis. This method can reduce carotid clamping time and lowers the risk of ischemic stroke. Meantime,it preserves the integrity of the adventitia at the bifurcation of carotid artery,reduces the chance of restenosis. Moreover,it might be helpful to prevent postoperative CHS due to reducing damage to the carotid body and carotid sinus nerve.

Objective:To study the correlation between different body weight metabolic phenotypes and their changes and new-onset hyperuricemia in physical examination population.Methods:This study was a retrospective cohort study. A total of 31 956 people who underwent routine physical examination and met the inclusion and exclusion criteria at the Health Management Center of the Second Affiliated Hospital of Dalian Medical University from January 1, 2014 to August 31, 2022 were selected as the study subjects to establish a dynamic physical examination cohort. The end point of follow-up was new-onset hyperuricemia or the end of follow-up period. Cox regression stepwise fitting model was used to analyze the risk of different body weight metabolic phenotypes and hyperuricemia, and stratified analysis was performed for gender. According to body weight metabolic phenotype, the subjects were divided into normal metabolism and normal weight(NMNW) group, normal metabolism and obesity (NMO) group, abnormal metabolism and normal weight (AMNW) group and abnormal metabolism and obesity (AMO) group. The risk of hyperuricemia was calculated according to the changes of body weight metabolic phenotype during the follow-up period. In the sensitivity analysis, the robustness of the results was verified by changing the diagnostic criteria for hyperuricemia, removing patients with hyperuricemia at the first year of follow-up, and removing subjects aged ≥65 years.Results:Compared with the NMNW group, the risk of hyperuricemia in the NMO group, AMNW group and AMO group increased by 78.9%, 61.3%, 115.4%, respectively ( χ2=272.88, 128.15, 496.12, all P<0.001). Patients who were initially classified as NMNW at baseline, if transitioned to NMO or AMO by the follow-up endpoint, their risk of hyperuricemia increased by 122.5% ( χ2=8.01, P<0.05) and 137.4% ( χ2=15.99, P<0.001), respectively. When the baseline AMNW group changed to AMO, the risk of hyperuricemia was increased by 119.2% ( χ2=6.63, P<0.05). For patients with AMO as baseline, if they turned into NMNW and AMNW at the end of follow-up, their risk of hyperuricemia would decrease by 58.3% ( χ2=43.67, P<0.001) and 27.2% ( χ2=16.07, P<0.001). Patients with a baseline of NMO who transitioned to NMNW and AMNW at the follow-up endpoint had their risk of developing hyperuricemia decreased by 36.7% ( χ2=25.35, P<0.001) and 30.9% ( χ2=9.70, P<0.05), respectively. Conclusions:The transition from metabolic health and non-overweight obesity to metabolic abnormalities and overweight obesity is associated with an increased risk of hyperuricemia, and improvements in metabolic health or weight are associated with a decreased risk of hyperuricemia.

Objective:To explore the relationship between weight change and the development of hyperuricemia (HUA) in adults receiving health checkups.Methods:A retrospective cohort study. A total of 37 722 subjects who underwent two or more health checkups at the Health Management Center of the Second Affiliated Hospital of Dalian Medical University from January 2014 to December 2022 were included, and the general information and laboratory findings at the time of the initial health checkups and follow-up were collected. Weight change was defined as the ratio of difference between the weight at the last follow-up and the baseline weight to baseline weight. The subjects were grouped with weight change: significant weight loss group (weight change ≤-5.0%), mild weight loss group (-5.0%

Objective:To investigate the association between different dietary patterns and subtypes of metabolic associated fatty liver disease(MAFLD).Methods:A total of 6 022 check-ups at the health management center of the Second Hospital of Dalian Medical University from January 2022 to March 2023 were selected as study subjects. MAFLD was categorised into three subtypes: overweight/obese type, metabolic disorder type, and diabetic type. Factor analysis was used to extract dietary patterns. Logistic regression was used to assess the impact of dietary patterns on MAFLD occurrence, constructing interaction models between dietary patterns intake and age, gender, and physical exercise levels. Results:Four dietary patterns were extracted based on feature sorting after factor analysis and were named as the high-quality protein pattern, the fruit-vegetable pattern, egg-aquatic pattern, and the processed meat pattern. Regression analysis of the unadjusted model showed that overweight/obese and diabetic types of MAFLD were negatively associated with the high-quality protein mode, while model-adjusted regression analysis showed that the processed meat pattern was positively associated with the risk of MAFLD, and fruit-vegetable pattern was positively associated with overweight/obese MAFLD( P<0.05). The results of subgroup analyses suggested that female( OR=1.55, 95% CI 1.14-2.15) with a high intake of pickle pattern had a higher risk of overweight/obese MAFLD than male( OR=1.18, 95% CI 1.02-1.49). Conclusion:High-quality protein pattern was negatively correlated with MAFLD, whereas fruit-vegetable pattern and processed meat pattern were positively correlated with MAFLD. Female with high consumption of processed meat pattern are more likely to develop overweight/obesity MAFLD compared with male. It is recommended that people with MAFLD reduce their intake of processed products and high-fructose food, and consume adequate amounts of high-quality protein food to maintain a balanced diet.

Objective:To investigate the relationship between obesity and incident chronic kidney disease(CKD) in a population undergoing health check-ups.Methods:This is a retrospective cohort study. A total of 31 251 participants who had at least 2 health physical examinations in the Health Management Center of the Second Affiliated Hospital of Dalian Medical University from January 2017 to December 2022 and met the inclusion criteria were selected. The participants were divided into normal body weight group, overweight group, and obese group according to baseline body mass index. Cox proportional hazard regression model was used to analyze the relationship between obesity and new-onset CKD, and the dose-response relationship between body mass index and CKD was analyzed with restricted cubic splines.Results:Multivariate Cox regression analysis showed that the risk of developing CKD increased by 13%( HR=1.13, 95% CI 1.01-1.25) and 55%( HR=1.55, 95% CI 1.36-1.76) in the overweight and obese group compared to the normal weight group. Subgroup analysis indicated that obese women had a higher risk of developing CKD compared to men. There was a " U-shaped" correlation between body mass index and CKD in male population, with the lowest risk of CKD occurring at body mass index of 19.6-24.2 kg/m 2. In women, the relationship between body mass index and CKD was approximately linear, with the risk of CKD gradually increasing when body mass index exceeded 22.5 kg/m 2. Conclusions:Obesity is an independent risk factor for new-onset CKD, and obese women have a higher risk of developing CKD than men. Regarding CKD prevention, men are advised to maintain a higher level of body weight within the normal range of body mass index, while women are encouraged to control their weight to a lower level within the normal body mass index range.