1.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.
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.Application of` the variable angle traction method by using clip with dental in super minimally invasive non full thickness resection of early gastric cancer
Qun SHAO ; Xiangdong WANG ; Ke HAN ; Jinping LI ; Zhaobei CAI ; Enqiang LINGHU ; Qianqian CHEN
Chinese Journal of Postgraduates of Medicine 2024;47(3):221-225
Objective:Assisted traction technology is effective in increasing the rate of super minimally invasive surgery (SMIS) in patients with early gastric cancer (EGC), and shortening the operator′s learning curve. We adopt the variable angle traction technique of tissue clamp dental floss as a traction technique in this research.Methods:Patients with early gastric cancer who were treated with SMIS - non full layer resection of EGC were enrolled in the First Medical Center of Chinese PLA General Hospital from January 2022 to June 2023. This research was carried out by experts at the same level. It was divided into two groups: traction and non-traction. Submucosal detachment time (SDT), submucosal detachment rate (SDS), lamina propria exposure, muscularis propria defect (MPD), bleeding during operation, block resection, surgical resection, hand operation expenses, and surgical instruments were recorded.Results:Nine patients adopted variable angle traction, and 9 patients did not. The overall resection rate and curative resection rate of both groups were 100%. The mean SDT time was 28.00 (21.00, 34.00) min in traction group and 56.00 (40.00, 85.00) min in non traction group. And it had statistical significance ( P = 0.005). The SDS was (0.58 ± 0.21) cm 2/min in traction group and (0.23 ± 0.10) cm 2/min in non-traction group. And it had statistical significance ( P<0.05). Exposure of intrinsic muscle layer (IML): 8 cases in the traction group and 6 cases in the non-traction group. Intraoperative IML injury: in the traction group, 8 cases were MPD-0 and 1 case was MPD-Ft; in the non-traction group, 4 cases were MPD-0, 1 case was MPD-Pt, and 4 cases were MPD-Ft. There was no statistical difference between the two groups in terms of intraoperative bleeding, hospitalization expenses, surgical expenses, and the total hospitalization time. There were no serious adverse reactions or outcomes. Conclusions:The variable angle traction method accelerates SDT and SDS for SMIS-non full layer resection of EGC. It has the advantages of the sufficient separation of IML and mucosal layer, the deeper dissection depth, the low injury of IML, low intraoperative bleeding, and no additional medical costs. Therefore, this method can become an auxiliary treatment technology for SMIS.
5.Efficacy evaluation of extending or switching to tenofovir amibufenamide in patients with chronic hepatitis B: a phase Ⅲ randomized controlled study
Zhihong LIU ; Qinglong JIN ; Yuexin ZHANG ; Guozhong GONG ; Guicheng WU ; Lvfeng YAO ; Xiaofeng WEN ; Zhiliang GAO ; Yan HUANG ; Daokun YANG ; Enqiang CHEN ; Qing MAO ; Shide LIN ; Jia SHANG ; Huanyu GONG ; Lihua ZHONG ; Huafa YIN ; Fengmei WANG ; Peng HU ; Xiaoqing ZHANG ; Qunjie GAO ; Chaonan JIN ; Chuan LI ; Junqi NIU ; Jinlin HOU
Chinese Journal of Hepatology 2024;32(10):883-892
Objective:In chronic hepatitis B (CHB) patients with previous 96-week treatment with tenofovir amibufenamide (TMF) or tenofovir disoproxil fumarate (TDF), we investigated the efficacy of sequential TMF treatment from 96 to 144 weeks.Methods:Enrolled subjects who were previously assigned (2:1) to receive either 25 mg TMF or 300 mg TDF with matching placebo for 96 weeks received extended or switched TMF treatment for 48 weeks. Efficacy was evaluated based on virological, serological, biological parameters, and fibrosis staging. Statistical analysis was performed using the McNemar test, t-test, or Log-Rank test according to the data. Results:593 subjects from the initial TMF group and 287 subjects from the TDF group were included at week 144, with the proportions of HBV DNA<20 IU/ml at week 144 being 86.2% and 83.3%, respectively, and 78.1% and 73.8% in patients with baseline HBV DNA levels ≥8 log10 IU/ml. Resistance to tenofovir was not detected in both groups. For HBeAg loss and seroconversion rates, both groups showed a further increase from week 96 to 144 and the 3-year cumulative rates of HBeAg loss were about 35% in each group. However, HBsAg levels were less affected during 96 to 144 weeks. For patients switched from TDF to TMF, a substantial further increase in the alanine aminotransferase (ALT) normalization rate was observed (11.4%), along with improved FIB-4 scores.Conclusion:After 144 weeks of TMF treatment, CHB patients achieved high rates of virological, serological, and biochemical responses, as well as improved liver fibrosis outcomes. Also, switching to TMF resulted in significant benefits in ALT normalization rates (NCT03903796).
6.Safety profile of tenofovir amibufenamide therapy extension or switching in patients with chronic hepatitis B: a phase Ⅲ multicenter, randomized controlled trial
Zhihong LIU ; Qinglong JIN ; Yuexin ZHANG ; Guozhong GONG ; Guicheng WU ; Lvfeng YAO ; Xiaofeng WEN ; Zhiliang GAO ; Yan HUANG ; Daokun YANG ; Enqiang CHEN ; Qing MAO ; Shide LIN ; Jia SHANG ; Huanyu GONG ; Lihua ZHONG ; Huafa YIN ; Fengmei WANG ; Peng HU ; Xiaoqing ZHANG ; Qunjie GAO ; Peng XIA ; Chuan LI ; Junqi NIU ; Jinlin HOU
Chinese Journal of Hepatology 2024;32(10):893-903
Objective:In chronic hepatitis B (CHB) patients with previous 96-week treatment with tenofovir amibufenamide (TMF) or tenofovir disoproxil fumarate (TDF), we investigated the safety profile of sequential TMF treatment from 96 to 144 weeks.Methods:Enrolled subjects that previously assigned (2:1) to receive either 25 mg TMF or 300 mg TDF with matching placebo for 96 weeks received extending or switching TMF treatment for 48 weeks. Safety profiles of kidney, bone, metabolism, body weight, and others were evaluated.Results:666 subjects from the initial TMF group and 336 subjects from TDF group with at least one dose of assigned treatment were included at week 144. The overall safety profile was favorable in each group and generally similar between extended or switched TMF treatments from week 96 to 144. In subjects switching from TDF to TMF, the non-indexed estimated glomerular filtration rate (by non-indexed CKD-EPI formula) and creatinine clearance (by Cockcroft-Gault formula) were both increased, which were (2.31±8.33) ml/min and (4.24±13.94) ml/min, respectively. These changes were also higher than those in subjects with extending TMF treatment [(0.91±8.06) ml/min and (1.30±13.94) ml/min]. Meanwhile, switching to TMF also led to an increase of the bone mineral density (BMD) by 0.75% in hip and 1.41% in spine. On the other side, a slight change in TC/HDL ratio by 0.16 (IQR: 0.00, 0.43) and an increase in body mass index (BMI) by (0.54±0.98) kg/m 2 were oberved with patients switched to TMF, which were significantly higher than that in TMF group. Conclusion:CHB patients receiving 144 weeks of TMF treatment showed favorable safety profile. After switching to TMF, the bone and renal safety was significantly improved in TDF group, though experienceing change in metabolic parameters and weight gain (NCT03903796).
7.Effect of tail suspension simulated weightlessness on DNA methylation profiles in liver and colon of mice
Yan LU ; Mingzhou GUO ; Huikai LI ; Qianqian CHEN ; Xiaofeng QIU ; Enqiang LINGHU
Space Medicine & Medical Engineering 2024;35(1):47-51
Objective This study uses whole-genome methylation capture sequencing technology to screen differential sites and regions of gene methylation in mouse liver and colon under simulated weightlessness conditions to reveal the specific impact of weightlessness on gene methylation.Methods Six 8-week-old male C57BL/6J mice were randomized into the tail suspension group and the control group,with 3 in each.The 3 mice in the tail suspension group recieved tail suspension for simulated weightlessness for 42 days.After the experiment,DNA was extracted from liver and colon tissue and analyzed using genome-wide methylation capture sequencing technology.Results DNA analysis of liver tissue showed that a total of 7 517 differentially methylated sites and 997 differentially methylated regions were found,involving 4 892 genes.DNA analysis of colon tissue revealed 70 340 differentially methylated sites and 12 004 differentially methylated regions,affecting 12 877 genes.GO and KEGG path analysis revealed that these differentially methylated genes were mainly involved in protein binding,cell adhesion,cell activation,and various metabolic pathways.Conclusion This study successfully identified differential methylation sites and regions in mouse liver and colon under simulated weightlessness conditions through high-throughput sequencing technology.These findings help to further understand the impact of long-term space residence on biological gene methylation.It provides new research ideas for the prevention and early treatment of space flight-related diseases.
8.Research progress of microgravity effect on liver and colon
Yan LU ; Mingzhou GUO ; Huikai LI ; Qianqian CHEN ; Xiaofeng QIU ; Enqiang LINGHU
Space Medicine & Medical Engineering 2024;35(4):268-272
With the increasing maturity and progress of China's space technology,astronauts can stay longer in the space station and complete more complex space experiments and tasks.In the Microgravity(MG)environment of space,the digestive system of astronauts is inevitably affected,especially the liver and colon,and there are many physiological and pathological changes.MG can affect liver metabolic function,cell proliferation and differentiation,oxidative stress response and inflammatory factor levels.MG can disrupt the intestinal barrier of the colon,intestinal flora and microecology,intestinal immunity,and the gut-liver axis.However,the existing studies on the effects of MG on liver and colon are not completely clear,and there is a lack of reliable diagnostic indicators for the pathological changes of both.Therefore,in order to explore the damage mechanism of MG on liver and colon and ensure the digestive system health of astronauts,this paper reviews the research progress on the effects of MG on liver and colon.
9.The occurrence and progress of immune inflammatory response involved in gastroesophageal reflux disease
Qianqian CHEN ; Yi LI ; Enqiang Hu LING
Chinese Journal of Postgraduates of Medicine 2023;46(4):311-316
Objective:To investigate the role of immune and inflammatory responses in the pathogenesis of gastroesophageal reflux disease (GERD).Methods:Fifteen patients with GERD who underwent biopsy and histopathology during painless gastroscopy in the digestive endoscopy center of the General Hospital of the PLA from December 2018 to September 2019 were analyzed retrospectively. They were divided into three groups: 6 cases of non erosive reflux disease (NERD), 8 cases of reflux esophagitis (RE) and 1 case of RE with high-grade intraepithelial neoplasia (RE-HIN). HE staining was used to analyze the inflammatory reaction of each group. The expression of cyclooxygenase-2(COX-2), inducible nitric oxide synthase (iNOS), interleukin (IL)-1β, myeloperoxidase (MPO), IL-4, nuclear factor kappa-B(NF-κB), IL-8, reactive oxygen species (ROS-1) were monitored by immunohistochemistry. Chi square test was used to analyze the positive rate of immune and inflammatory indexes in each group.Results:The three groups showed mild and moderate inflammatory cell infiltration, mostly lymphocyte infiltration, and basal cell hyperplasia in 3 cases. There was no significant difference between inflammatory cell infiltration, basal hyperplasia and inflammatory grade in NERD and RE( P>0.05). Immune and inflammatory factors COX-2(positive rate:NERD 4/6, RE4/8, RE-HIN 1/1), iNOS(positive rate:NERD 4/6, RE 3/8, RE-HIN 0), IL-1β(positive rate:NERD 6/6, RE 7/8, RE-HIN 1/1), MPO(positive rate:NERD 4/6, RE 7/8, RE-HIN 1/1), IL-4(positive rate:NERD 3/6, RE 4/8, RE-HIN 0), IL-8(positive rate:NERD 2/6, RE 6/8, RE-HIN 1/1), ROS-1(positive rate:NERD 3/6, RE 1/8, RE-HIN 0) and signal pathway NF- κ B (positive rate:NERD 4/6, RE 8/8, RE-HIN 1/1) were positive in three groups. The expressions of IL-1β, MPO and NF-κB were statistically significant among the three groups ( P<0.05). Conclusions:There is an inflammatory cascade mediated by immune inflammatory factors and mediators in GERD patients, and NF-κB signaling pathway is involved. It provides a basis for finding targets to block immune and inflammatory responses in the later stage to treat GERD.
10.Endoscopic super minimally invasive surgery for superficial neoplasia associated with submucosal tumor at the same position of upper digestive tract
Baojie ZHU ; Ningli CHAI ; Shengzhen LIU ; Qianqian CHEN ; Enqiang LINGHU
Chinese Journal of Digestive Endoscopy 2023;40(8):610-615
Objective:To explore the clinical characteristics of superficial neoplasia associated with submucosal tumor (SMT) located at the same position and the efficacy of endoscopic super minimally invasive surgery (SMIS).Methods:Data of 9 patients who were diagnosed as having superficial neoplasia associated with SMT at the same position in the upper digestive tract and treated with digestive endoscopic SMIS at the First Medical Center of PLA General Hospital from January 2011 to December 2021 were retrospectively analyzed. Data including basic information, endoscopic diagnosis and treatment, pathological results and follow-up of these patients were collected to analyze their clinicopathological characteristics. The postoperative pathology and incidence of complications were used as the gold standard to assess the effectiveness and safety of SMIS.Results:In the 9 patients, there were 8 males and 1 female with mean age of 61.6±11.7 years. The main symptoms were abdominal pain in 3 cases, abdominal discomfort in 2 cases, and dysphagia in 1 case. Seven patients were diagnosed as having superficial neoplasia before surgery, while SMT was found during surgery. One patient with superficial neoplasia associated with SMT and 1 with SMT were diagnosed before the surgery. The common sites of the lesion were esophagus (3 cases), gastric antrum (3 cases), cardia (2 cases) and fundus (1 case). The Paris classification of all lesions was type Ⅰ, Ⅱa or combinations. The most common pathological type was early cancer with leiomyoma in 5 cases. All lesions met the criteria of en bloc resection. One lesion had positive lateral margin with low-grade intraepithelial neoplasia, four were all completely resected. No complications such as bleeding, perforation or infection occurred in this study. Follow-up date were available in all cases with a mean period of 19-81 months and no recurrence or metastasis was discovered.Conclusion:The symptoms of patients with superficial neoplasia associated with SMT located at the same position are often atypical. The endoscopic type of lesions is usually protrusion or partial protrusion. Most are diagnosed as having superficial neoplasia before the surgery, and SMT are usually found coincidentally. The most common pathological type is early cancer with leiomyoma. SMIS is safe and effective for the complex lesion.

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