1.Prospective study of association between dietary macronutrients and lung function in school aged children
LI Lu, CHEN Mengxue, LI Ruirui, LIU Xueting, WANG Xiaoyu, XU Yujie, XIONG Jingyuan, CHENG Guo
Chinese Journal of School Health 2025;46(2):200-204
Objective:
To explore the longitudinal associations between dietary macronutrients and lung function in schoolaged children, so as to provide the nutritional research evidence for promoting children s lung health.
Methods:
In November 2021, two primary schools located in Chengdu, Sichuan Province were selected from the Southwest China Childhood Nutrition and Growth (SCCNG) cohort by a stratified cluster random sampling method, enrolling a total of 1 112 school aged children aged 8 to 13 years. At baseline, the dietary and sociodemographic characteristics of the children were assessed. One year later, the forced vital capacity (FVC) of the children was measured and converted into Z scores (FVC- Z ), while the vital capacity index (VCI) was also calculated. Generalized linear regression analysis was employed to examine the associations between dietary macronutrients and lung function, considering interactions with gender and age, followed by stratified analysis.
Results:
After adjusting for confounding factors, the analysis results of the generalized linear regression model showed that the carbohydrate energy ratio was negatively correlated with FVC- Z ( β =-0.02) and VCI ( β =-0.16), while the fat energy ratio showed a positive correlation with FVC- Z ( β =0.03) and VCI ( β =0.23) ( P <0.05). The protein energy ratio was positively correlated with FVC- Z ( β =0.09) and VCI ( β =0.60) specifically in girls ( P <0.05). Additionally, there was an interaction effect of age on the associations between macronutrients and lung function ( P <0.01); in children aged 8-9 and 10-11, the carbohydrate energy supply ratio was negatively correlated with FVC- Z ( β =-0.04, -0.03) and VCI ( β =-0.29, -0.21), and fat energy supply ratio was positively correlated with FVC- Z ( β =0.07, 0.05) and VCI ( β =0.46, 0.32) ( P <0.05).
Conclusions
There are age and sex differences in the association of dietary macronutrients with lung function, with a low carbohydrate, high fat diet promoting lung function in children. Additionally, protein intake appears to have a positive influence on the lung function of girls. The early school age period may represent a critical window for dietary interventions aimed at promoting lung health.
2.Association of Genetically Predicted Obesity and Stool Frequency: Evidence From an Observational and Mendelian Randomization Study
Ke HAN ; Xiangyao WANG ; Shimin CHEN ; Xiaotong NIU ; Yan WANG ; Jingyuan XIANG ; Nan RU ; Miao LIU ; Ningli CHAI ; Enqiang LINGHU
Journal of Neurogastroenterology and Motility 2025;31(2):267-275
Background/Aims:
Obesity is associated with several gastrointestinal (GI) disorders and has been identified as a potential risk factor for various GI symptoms. Bowel frequency is an important indicator of bowel function. However, the causal link between obesity and gastrointestinal motility remains uncertain. This study aims to determine the causal effect of overall and central obesity on stool frequency.
Methods:
Four obesity-related anthropometric indicators–body mass index, body fat percentage, waist circumference (WC), and waist-tohip ratio (WHR)–were investigated. Individual-level baseline information from the UK Biobank was used to explore observational associations between obesity and stool frequency. Additionally, summary-level data from published genome-wide association studies were subjected to two-sample Mendelian randomization (MR) analyses to examine causal associations.
Results:
For all 4 indicators of obesity, higher levels of obesity were associated with more frequent bowel movements after adjusting for demographic characteristics, lifestyle, and dietary factors. After rigorous screening, 482 body mass index single nucleotide polymorphisms (SNPs), 7 body fat percentage SNPs, 48 WC SNPs, and 287 WHR SNPs were identified as instrument variables for MR analysis. The MR results were generally consistent with observational findings, proving that the associations observed in the overall obesity indicators were causal. For central obesity, the association between WHR and stool frequency remained consistent in both analysis phases, whereas WC showed a multidirectional association.
Conclusions
Obesity-related anthropometric indicators were causally associated with increased stool frequency in the overall and central obesity groups. Weight loss could be a potential approach to improve gastrointestinal regularity in individuals with obesity.
3.Association of Genetically Predicted Obesity and Stool Frequency: Evidence From an Observational and Mendelian Randomization Study
Ke HAN ; Xiangyao WANG ; Shimin CHEN ; Xiaotong NIU ; Yan WANG ; Jingyuan XIANG ; Nan RU ; Miao LIU ; Ningli CHAI ; Enqiang LINGHU
Journal of Neurogastroenterology and Motility 2025;31(2):267-275
Background/Aims:
Obesity is associated with several gastrointestinal (GI) disorders and has been identified as a potential risk factor for various GI symptoms. Bowel frequency is an important indicator of bowel function. However, the causal link between obesity and gastrointestinal motility remains uncertain. This study aims to determine the causal effect of overall and central obesity on stool frequency.
Methods:
Four obesity-related anthropometric indicators–body mass index, body fat percentage, waist circumference (WC), and waist-tohip ratio (WHR)–were investigated. Individual-level baseline information from the UK Biobank was used to explore observational associations between obesity and stool frequency. Additionally, summary-level data from published genome-wide association studies were subjected to two-sample Mendelian randomization (MR) analyses to examine causal associations.
Results:
For all 4 indicators of obesity, higher levels of obesity were associated with more frequent bowel movements after adjusting for demographic characteristics, lifestyle, and dietary factors. After rigorous screening, 482 body mass index single nucleotide polymorphisms (SNPs), 7 body fat percentage SNPs, 48 WC SNPs, and 287 WHR SNPs were identified as instrument variables for MR analysis. The MR results were generally consistent with observational findings, proving that the associations observed in the overall obesity indicators were causal. For central obesity, the association between WHR and stool frequency remained consistent in both analysis phases, whereas WC showed a multidirectional association.
Conclusions
Obesity-related anthropometric indicators were causally associated with increased stool frequency in the overall and central obesity groups. Weight loss could be a potential approach to improve gastrointestinal regularity in individuals with obesity.
4.Association of Genetically Predicted Obesity and Stool Frequency: Evidence From an Observational and Mendelian Randomization Study
Ke HAN ; Xiangyao WANG ; Shimin CHEN ; Xiaotong NIU ; Yan WANG ; Jingyuan XIANG ; Nan RU ; Miao LIU ; Ningli CHAI ; Enqiang LINGHU
Journal of Neurogastroenterology and Motility 2025;31(2):267-275
Background/Aims:
Obesity is associated with several gastrointestinal (GI) disorders and has been identified as a potential risk factor for various GI symptoms. Bowel frequency is an important indicator of bowel function. However, the causal link between obesity and gastrointestinal motility remains uncertain. This study aims to determine the causal effect of overall and central obesity on stool frequency.
Methods:
Four obesity-related anthropometric indicators–body mass index, body fat percentage, waist circumference (WC), and waist-tohip ratio (WHR)–were investigated. Individual-level baseline information from the UK Biobank was used to explore observational associations between obesity and stool frequency. Additionally, summary-level data from published genome-wide association studies were subjected to two-sample Mendelian randomization (MR) analyses to examine causal associations.
Results:
For all 4 indicators of obesity, higher levels of obesity were associated with more frequent bowel movements after adjusting for demographic characteristics, lifestyle, and dietary factors. After rigorous screening, 482 body mass index single nucleotide polymorphisms (SNPs), 7 body fat percentage SNPs, 48 WC SNPs, and 287 WHR SNPs were identified as instrument variables for MR analysis. The MR results were generally consistent with observational findings, proving that the associations observed in the overall obesity indicators were causal. For central obesity, the association between WHR and stool frequency remained consistent in both analysis phases, whereas WC showed a multidirectional association.
Conclusions
Obesity-related anthropometric indicators were causally associated with increased stool frequency in the overall and central obesity groups. Weight loss could be a potential approach to improve gastrointestinal regularity in individuals with obesity.
5.Mechanism of Xiezhuo Jiedu Formula in Treating Ulcerative Colitis Through Pyroptosis Regulation Based on Bioinformatics and Animal Experiments
Qiang CHUAI ; Wenjing ZHAI ; Shijie REN ; Xiaomeng LANG ; Xin KANG ; Wenli WEI ; Jingyuan LIU ; Jianping LIU ; Jie REN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(16):105-113
ObjectiveThis study aims to explore the potential mechanism of the Xiezhuo Jiedu formula in regulating pyroptosis for the treatment of ulcerative colitis (UC) using bioinformatics and in vivo animal experiments. MethodsDifferentially expressed genes (DEGs) in colon tissues of UC patients were retrieved from the Gene Expression Omnibus (GEO) database. Pyroptosis-related genes were obtained from the GEO and GeneCards databases. The intersection of these datasets yielded pyroptosis-related DEGs (Pyro-DEGs). Pyro-DEGs were subjected to Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis using the Metascape database. A protein-protein interaction (PPI) network was constructed using the STRING database. Least absolute shrinkage and selection operator (LASSO) prediction model and receiver operating characteristic (ROC) analysis were conducted to identify core Pyro-DEGs with diagnostic and therapeutic potential. Immune infiltration analysis of the UC datasets was performed using the deconvolution method (CIBERSORT), along with correlation analysis with core Pyro-DEGs. Sixty male Sprague-Dawley (SD) rats were randomly divided into a control group, a model group, high-, medium-, and low-dose groups of Xiezhuo Jiedu formula (26.64, 13.32, 6.66 g·kg-1), and a mesalazine group (0.27 g·kg-1), with 10 rats in each group. UC was established by intrarectal administration of 3,5-trinitrobenzenesulfonic acid (TNBS) dissolved in ethanol. The control and model groups were given distilled water by gavage, while the treatment groups were administered the corresponding drugs for 7 consecutive days. Hematoxylin-eosin (HE) staining was used to observe the colon histopathology. Enzyme-linked immunosorbent assay (ELISA) was used to detect the levels of inflammatory factors such as interleukin-1β (IL-1β), IL-10, IL-18, and transforming growth factor-β (TGF-β). Immunohistochemistry (IHC) and Western blot were applied to detect the expression of Caspase-1, gap junction alpha-1 protein (GJA1), peroxisome proliferator-activated receptor gamma (PPARG), and S100 calcium-binding protein A8 (S100A8). Real-time quantitative polymerase chain reaction (Real-time PCR) was utilized to measure mRNA expression of Caspase-1, GJA1, PPARG, and S100A8. Western blot was performed to assess protein expression levels of Caspase-1, GJA1, PPARG, and S100A8. ResultsGEO datasets GSE87466 and GSE87473 yielded 64 Pyro-DEGs. KEGG analysis indicated that these genes were enriched in the NOD-like receptor signaling pathway, tumor necrosis factor (TNF) signaling pathway, and hypoxia-inducible factor 1 (HIF-1) signaling pathway. Four core Pyro-DEGs (Caspase-1, GJA1, PPARG, and S100A8) were identified. Immune infiltration analysis showed that expression of these genes was positively correlated with mast cells, neutrophils, M0 macrophages, M1 macrophages, and dendritic cells. Animal experimental results indicated that compared with the control group, the model group had significantly increased levels of IL-1β and IL-18, significantly decreased levels of IL-10 and TGF-β. The model group showed enhanced Caspase-1, GJA1, and S100A8 staining, and significantly increased mRNA and protein expression of Caspase-1, GJA1, and S100A8 (P<0.01). In contrast, the expression of PPARG was reduced in the model group (P<0.01). After treatment, all dosage groups showed varying degrees of improvement (P<0.05, P<0.01), with the high-dose group showing the most significant improvement (P<0.01). ConclusionCaspase-1, GJA1, PPARG, and S100A8 are core Pyro-DEGs closely associated with the pathogenesis of UC. These genes may collaborate with immune cells such as mast cells, neutrophils, and M0 macrophages to mediate disease development. The Xiezhuo Jiedu formula may regulate the expression of core Pyro-DEGs through the NOD-like receptor, TNF, and HIF-1 core signaling pathways, thereby modulating immune homeostasis in UC rats and effectively alleviating UC.
6.Characteristics of individuals attending HIV voluntary counseling and testing clinics in Inner Mongolia Autonomous Region
LI Yao ; YANG Jingyuan ; YANG Hong ; LI Xiangchun ; KONG Ruiqin ; LIU Jing ; BAI Baobao ; ZHANG Yanping ; LI Hui
Journal of Preventive Medicine 2025;37(4):356-360
Objective:
To investigate the characteristics and HIV confirmed positive status among individuals attending HIV voluntary counseling and testing (VCT) clinics in Inner Mongolia Autonomous Region, so as to provide the basis for enhancing interventions targeting high-risk populations for AIDS.
Methods:
Demographic information, reasons for consultation, consulting institutions, and HIV antibody testing data of individuals attending VCT clinics in Inner Mongolia Autonomous Region from 2019 to 2023 were collected through the VCT database of the Chinese Center for Disease Control and Prevention. The characteristics of individuals attending VCT were described. Factors affecting HIV confirmed positive among VCT clinic attendees were analyzed using a multivariable logistic regression model.
Results:
A total of 249 919 individuals attended VCT clinics in Inner Mongolia Autonomous Region from 2019 to 2023, including 128 069 males (51.24%) and 121 850 females (48.76%). The majority of attendees were aged 25-<35 years, accounting for 92 445 cases (36.99%). Among them, 785 cases were confirmed as HIV positive, with a positivity rate of 0.31%. Multivariable logistic regression analysis revealed that males (OR=4.787, 95%CI: 3.562-6.434), 45-<65 years of age (45-<55 years, OR=7.723, 95%CI: 1.786-33.406; 55-<65 years, OR=7.689, 95%CI: 1.757-33.653), being unmarried (OR=2.143, 95%CI: 1.580-2.906), junior high school education or below (OR=1.147, 95%CI: 1.042-2.430), having the history of high-risk behaviors or exposure risks (commercial heterosexual behaviors, OR=2.717, 95%CI: 1.707-4.324; non-commercial non-fixed heterosexual behaviors, OR=5.421, 95%CI: 3.763-7.809; homosexual behaviors, OR=70.774, 95%CI: 48.409-103.473; having an HIV-positive spouse/fixed partner/mother, OR=100.024, 95%CI: 62.490-160.100; drug injection, OR=5.366, 95%CI: 2.213-13.014), and seeking general hospitals or traditional Chinese medicine hospitals (OR=1.973, 95%CI: 1.650-2.360) were associated with a higher risk of HIV confirmed positive.
Conclusions
HIV confirmed positive among individuals attending VCT clinics in Inner Mongolia Autonomous Region is associated with gender, age, marital status, educational level, reasons for consultation, and consulting institutions. It is recommended to strengthen health education and targeted interventions for high-risk populations to reduce the risk of HIV infection.
7.Mechanism of Modified Guizhi Fulingwan in Regulating Mitochondrial Apoptosis Pathway Through PTEN/PI3K/Akt Pathway to Prevent Colorectal Adenoma in Mice
Sujie JIA ; Longhui LIU ; Yifan ZHANG ; Xiaomeng LANG ; Jianping LIU ; Xin KANG ; Chaodi SUN ; Jingyuan LIU
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(19):10-20
ObjectiveTo investigate the effect and mechanism of modified Guizhi Fulingwan in preventing colorectal adenoma (CRA) in mice by regulating mitochondrial apoptosis pathway through the regulation of the phosphatase and tensin homolog (PTEN)/phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) pathway. MethodSixty SPF-grade male C57BL/6 mice were randomly divided into six groups: Normal group, model group, low, medium, and high dose groups of modified Guizhi Fulingwan (13, 26, 52 g·kg-1·d-1), and positive control aspirin group (0.015 g·kg-1·d-1). A mouse model of CRA was chemically induced using azoxymethane (AOM) and dextran sulfate sodium (DSS). During the modeling process, mice received modified Guizhi Fulingwan or aspirin. Body weight of mice was measured weekly during the treatment. After 9 weeks, the number of adenomas formed was observed. Serum levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β) were determined by enzyme-linked immunosorbent assay (ELISA). Hematoxylin-eosin (HE) staining was used to observe the histopathologic changes in adenoma tissues. The expression of Cyclin D1 and proliferative nuclear antigen (Ki67) was detected by immunohistochemistry (IHC). Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) was used to assess the apoptosis in adenoma tissues. Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) and Western blot were used to observe the mRNA and protein expression levels of PTEN, PI3K, Akt, phosphorylated PI3K (p-PI3K), phosphorylated Akt (p-Akt), B-cell lymphoma-2 (Bcl-2), Bcl-2 associated X protein (Bax), cytochrome C (Cyt C), Caspase-9, and caspase-3. ResultCompared with the normal group, the model group showed no significant change in body weight from week 1 to week 2, but a significant decrease from week 3 to week 9 (P<0.05,P<0.01). The colorectal length was significantly shortened, and the colorectal weight increased with visible varying sized tumor-like protrusions on the mucosal surface (P<0.01). Serum levels of TNF-α, IL-6, and IL-1β were elevated (P<0.01). Histopathology showed disordered epithelial gland structure, elongated nuclei with pathological mitosis, and numerous lymphocytic infiltrations in the lamina propria. The positive expression rates of Cyclin D1 and Ki67 were significantly increased (P<0.01), while the apoptosis rate of adenoma cells was significantly decreased (P<0.01). Expression levels of PI3K, Akt, Bcl-2 mRNA and proteins, as well as p-PI3K and p-Akt proteins, were significantly increased (P<0.01), whereas PTEN, Bax, Cyt C, Caspase-9, and Caspase-3 mRNA and protein levels were significantly decreased (P<0.05, P<0.01). Compared with the model group, all drug treatment groups showed an increase in body weight (P<0.01), decreased intestinal weight, increased colorectal length, reduced number of adenomas significantly (P<0.05, P<0.01), and significantly lowered serum levels of TNF-α, IL-6, and IL-1β (P<0.01). Histopathology indicated improved glandular structure and reduced neutrophil infiltration in the mucosal lamina propria. The positive expression rates of Cyclin D1 and Ki67 significantly decreased (P<0.01), while the apoptosis rate of adenoma cells significantly increased (P<0.05, P<0.01). Expression levels of PI3K, Akt, Bcl-2 mRNA and proteins, and p-PI3K and p-Akt proteins were significantly reduced (P<0.05, P<0.01), while PTEN, Bax, Cyt C, Caspase-9, and Caspase-3 mRNA and protein levels significantly increased (P<0.05, P<0.01). The high-dose modified Guizhi Fulingwan group exhibited the most significant intervention effects. ConclusionModified Guizhi Fulingwan may prevent CRA in mice by regulating the PTEN/PI3K/Akt signaling pathway and inducing the mitochondrial apoptosis pathway.
8.Low intramuscular adipose tissue index is a protective factor of all-cause mortality in maintenance dialysis patients
Jing ZHENG ; Shimei HOU ; Keqi LU ; Yu YAN ; Shuyan ZHANG ; Li YUAN ; Min LI ; Jingyuan CAO ; Yao WANG ; Min YANG ; Hong LIU ; Xiaoliang ZHANG ; Bicheng LIU ; Bin WANG
Chinese Journal of Nephrology 2024;40(2):101-110
Objective:To investigate the relationship between intramuscular adipose tissue index (IATI) calculated from computed tomography images at transverse process of the first lumbar and all-cause mortality in maintenance dialysis patients, and to provide a reference for improving the prognosis in these patients.Methods:It was a multicenter retrospective cohort study. The clinical data of patients who received maintenance hemodialysis or peritoneal dialysis treatment from January 1, 2017 to December 31, 2019 in 4 grade Ⅲ hospitals including Zhongda Hospital Affiliated to Southeast University, Taizhou People's Hospital Affiliated to Nanjing Medical University, Affiliated Hospital of Yangzhou University, and the Third Affiliated Hospital of Soochow University were retrospectively collected. IATI was calculated by low attenuation muscle (LAM) density/skeletal muscle density. The receiver-operating characteristic curve was used to determine the optimal cut-off value of IATI, and the patients were divided into high IATI group and low IATI group according to the optimal cut-off value. The differences of baseline clinical data and measurement parameters of the first lumbar level between the two groups were compared. The follow-up ended on December 23, 2022. The endpoint event was defined as all-cause mortality within 3 years. Kaplan-Meier survival curve and log-rank test were used to analyze the survival rates and the differences between the two groups. Multivariate Cox regression analysis models were used to analyze the association between IATI and the risk of all-cause mortality in maintenance dialysis patients. Multivariate logistic regression analysis model was used to analyze the influencing factors of high IATI.Results:A total of 478 patients were eligibly recruited in this study, with age of (53.55±13.19) years old and 319 (66.7%) males, including 365 (76.4%) hemodialysis patients and 113 (23.6%) peritoneal dialysis patients. There were 376 (78.7%) patients in low IATI (<0.42) group and 102 (21.3%) patients in high IATI (≥0.42) group. The proportion of age ≥ 60 years old ( χ2=24.746, P<0.001), proportion of diabetes mellitus ( χ2=5.570, P=0.018), fasting blood glucose ( t=-2.145, P=0.032), LAM density ( t=-3.735, P<0.001), LAM index ( t=-7.072, P<0.001), and LAM area/skeletal muscle area ratio ( Z=-9.630, P<0.001) in high IATI group were all higher than those in low IATI group, while proportion of males ( χ2=11.116, P<0.001), serum albumin ( Z=2.708, P=0.007) and skeletal muscle density ( t=12.380, P<0.001) were lower than those in low IATI group. Kaplan-Meier survival analysis showed that the 3-years overall survival rate of low IATI group was significantly higher than that in high IATI group (Log-rank χ2=19.188, P<0.001). Multivariate Cox regression analysis showed that IATI<0.42 [<0.42/≥0.42, HR(95% CI): 0.50 (0.31-0.83), P=0.007] was an independent protective factor of all-cause mortality, and age ≥60 years old [ HR (95% CI): 2.61 (1.60-4.23), P<0.001], diabetes mellitus [ HR (95% CI): 1.71 (1.06-2.78), P=0.029] and high blood neutrophil/lymphocyte ratio [ HR (95% CI): 1.04 (1.00-1.07), P=0.049] were the independent risk factors of all-cause mortality in maintenance dialysis patients. Stepwise Cox regression analysis showed that IATI<0.42 was still an independent protective factor of all-cause mortality in maintenance dialysis patients [<0.42/≥0.42, HR (95% CI): 0.45 (0.27-0.76), P=0.003]. Multivariate logistic regression analysis showed that low skeletal muscle density [ OR (95% CI): 0.84 (0.81-0.88), P<0.001] and high serum triglyceride [ OR (95% CI): 1.39 (1.07-1.82), P=0.015] were the independent influencing factors of IATI≥0.42. Conclusion:IATI<0.42 of the first lumbar level is an independent protective factor of all-cause mortality in maintenance dialysis patients. Localized myosteatosis within high-quality skeletal muscle may reduce the risk of all-cause mortality in these patients.
9.Effect of Jiuxin Pill (救心丸)on Exercise Tolerance and Quality of Life in Patients of Stable Angina Pectoris:A Randomized,Double-Blind,Placebo-Controlled,Multi-Center Clinical Trial
Xianliang WANG ; Mingjun ZHU ; Daimei NI ; Jianguang WU ; Yitao XUE ; Chenglong WANG ; Xiaohua DAI ; Qian LIN ; Jun LI ; Zhiqiang ZHAO ; Shuai WANG ; Yingfei BI ; Tongzuo LIU ; Zhou ZHOU ; Jingyuan MAO
Journal of Traditional Chinese Medicine 2024;65(24):2549-2557
ObjectiveTo evaluate the effect and safety of Jiuxin Pill (救心丸) on exercise tolerance and quality of life in patients with stable angina pectoris (SAP). MethodsA randomised, double-blind, placebo-controlled, multicentre study design was used to enroll 170 patients of SAP from nine centres, which were divided into 85 patients each in the trial group and control group with 1∶1 ratio. Both groups maintained the original western medicine treatment plan, and added Jiuxin Pill or placebo respectively, 2 pills (0.05 g) each time twicely for 28 days. The main outcomes were total exercise time (TED) in the exercise treadmill test and Seattle Angina Questionnaire (SAQ) scores including physical limitation (PL), angina stability (AS), angina frequency (AF), treatment satisfaction (TS), and disease perception (DP). The secondary outcomes were exercise treadmill test indicators including heart rate recovery in 1 min (HRR1), metabolic equivalents (METs), maximum magnitude of ST-segment depression, and the Borg rating of perceived exertion scale, the average number of angina attacks per week, withdrawal and reduction rate of nitroglycerin, traditional Chinese medicine syndrome scores, incidence of major adverse cardiovascular events. Safety indicators were evaluated and the occurrence of adverse events during the trial was recorded. Data was collected before treatment, day 28±2 in treatment period, and follow-up at day 56 which is 28±2 days after treatment period finished. ResultsEighty-four and eighty-five patients respectively from trial group and control group were included to the full analysis set (FAS) and safety analysis set (SS). Compared with the group before treatment and with the control group after treatment, the trial group had higher TED, HRR1, and METs, and lower maximum magnitude of ST-segment depression and Borg rating of perceived exertion scores after treatment (P<0.01). Compared with the group before treatment and with the control group after treatment and at follow-up, the total SAQ score and scores of AS, AF, TS and DP of the trial group after treatment and at follow-up elevated, while the average number of angina attacks per week and traditional Chinese medicine syndrome scores reduced (P<0.01). There was no statistically significant difference in the withdrawal and reduction rate of nitroglycerin between groups (P>0.05). Major adverse cardiovascular events occurred in 1 case (1/84, 1.19%) in the trial group and 1 case (1/85, 1.18%) in the control group, and the difference between groups was not statistically significant (P>0.05). A total of 3 cases of adverse events occurred in the trial group (3/84, 3.57%), and a total of 6 cases of adverse events occurred in the control group (6/85, 7.06%), and there was no statistically significant difference in the incidence of adverse events between groups (P>0.05). ConclusionIn the treatment of SAP, Jiuxin Pill combined with conventional western medicine can further enhance exercise tolerance, improve quality of life, and demonstrate great safety.
10.Mechanism of Xiezhuo Jiedu Recipe in Preventing Colorectal Adenoma in Mice Through miRNA-34a-5p/PI3K/Akt Signalling Pathway
Sujie JIA ; Chaodi SUN ; Yifan ZHANG ; Xiaomeng LANG ; Jianping LIU ; Xin KANG ; Shijie REN ; Jingyuan LIU
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(11):156-165
ObjectiveKey microRNAs (miRNAs) of colorectal adenoma (CRA) were identified and analyzed by bioinformatics methods, and differentially expressed genes (DEGs) were screened to construct regulatory relationships. The mechanism of Xiezhuo Jiedu recipe in preventing CRA was speculated and verified by animal experiments. MethodThe miRNAs dataset GSE50194 was obtained from the Gene Expression Omnibus (GEO) database of intestinal mucosal tissue of CRA patients, and the differentially expressed miRNAs were screened by GEO2R and Excel. TargetScan, miRTarbase, and miRDB databases were used to predict the target genes of the differentially expressed miRNAs, and an intersection was obtained. Key DEGs were screened through the STRING database and Cytoscape software, and the TRRUST database was used to predict downstream binding transcription factors (TFs). The mRNA intersection was enriched by gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) in the Metascape database. DIANA TOOLS were applied to perform KEGG enrichment analysis of key miRNAs, and the key signaling pathways were selected for animal experiments. In animal experiments, the CRA mice model was established by using sodium glycan sulfate (DSS) drinking combined with intraperitoneal injection of azomethane oxide (AOM), and Xiezhuo Jiedu recipe and aspirin were given by intragastric administration at the same time. The experiment lasted for nine weeks. The pathological changes in intestinal tissue were observed by hematoxylin-eosin (HE) staining. Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) was used to detect the mRNA expression of miR-34a-5p in adenoma tissue. Protein expression levels of phosphatidylinositol 3-kinase (PI3K), protein kinase B (Akt), phosphoryl-PI3K (p-PI3K), phosphoryl-Akt (p-Akt), and B cell lymphoma (Bcl)-2 were detected by Western blot. The expression of Cyclin D1 (CCND1) was detected by immunohistochemistry (IHC). In situ terminal transferase labeling (TUNEL) was used to detect apoptosis of adenoma tissue cells. ResultThe GEO database screened the GSE50194 dataset, and miR-34a-5p was selected as the research object from CRA and normal tissue. A total of 93 DEGs were selected. Among them, GO and KEGG enrichment analyses were closely related to biological processes such as transcriptional regulatory complex, RNA polymerase Ⅱ transcriptional regulatory complex, enzyme-linked receptor protein signaling pathway, and DNA-binding transcriptional activator activity, cancer pathway, PI3K/Akt pathway, etc. miR-34a-5p is mainly enriched in PI3K/Akt, cell cycle, and colorectal cancer pathways. Five key DEGs were screened out through the Matescape database, among which Bcl-2 and CCND1 were the key DEGs of miR-34a-5p. Further screening of the TFs of key DEGs revealed that E2F transcription factor 1 (E2F1) and tumor protein P53 (TP53) were the main TFs of Bcl-2 and CCND1. Animal experiments showed that Xiezhuo Jiedu recipe could effectively up-regulate mRNA level of miR-34a-5p, down-regulate the expression of PI3K, Akt, Bcl-2, p-PI3K, and p-Akt proteins in the intestinal tissue of CRA mice, down-regulate the positive expression rate of CCND1, and increase the apoptosis rate of intestinal epithelial cells. ConclusionIt is speculated that Xiezhuo Jiedu recipe may inhibit the abnormal proliferation and promote the apoptosis of intestinal epithelial cells in CRA mice by regulating the miR-34a-5p/PI3K/Akt signaling pathway, thus playing a role in the prevention of CRA.


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