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Advances in the understanding of the intestinal micro-environment and inflammatory bowel disease

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Chinese Medical Journal 2020年第7期133卷 834-841页

作者： Peng-Guang Yan jing-nan li Department of Gastroenterology Peking Union Medical College HospitalBeijing 100730China Key Laboratory of Gut Microbiota Translational Medicine Research Chinese Academy of Medical SciencesBeijing 100730China

The human gastrointestinal tract accommodates an entire micro-environment for divergent physiologic processes,the dysbiosis of this micro-ecology has a strong inter-action with the pathogenesis of inflammatory bowel disease(IBD).In the past few years,with the advances in the understanding of microbiome,its metabolites and further application of next generation sequencing,analysis of dynamic alteration of gut micro-environment was realized,which provides numerous information beyond simple microbiota structure or metabolites differences under chronic colitis *** subsequent intervention strategies targeting the modulation of intestinal micro-environment have been explored as a potential *** this review,we will summarize the recent knowledge about multi-dimensional dysbiosis,the inter-action between fungus and bacteria under inflamed mucosa,and the clinical application of probiotics and fecal microbiota transplantation as a promising therapeutic approach in IBD.

关键词： Intestinal micro-environment dysbiosis Inflammatory bowel disease Multi-omics Probiotics Fecal microbiota transplantation

Association between CYP24A1 polymorphisms and the risk of colonic polyps and colon cancer in a Chinese population

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World Journal of Gastroenterology 2017年第28期23卷 5179-5186页

作者： Xue-Qi Chen Jia-Yu Mao Wen-Bin li Jian li Hong Yang Jia-Ming Qian jing-nan li Department of Gastroenterology Peking Union Medical College Hospital Department of General Surgery Henan Cancer Hospital

AIM To determine the pathogenesis and potential single nucleotide polymorphisms(SNPs) as screening sites for colonic polyps,colon cancer and ulcerative colitis,and to analyze the possible association between these genetic polymorphisms and the three diseases. METHODS We evaluated genetic polymorphisms in 144 newly diagnosed colonic polyp patients,96 colon cancer patients and 44 ulcerative colitis patients. The four SNPs genotyped were rs4809957,rs6068816,rs6091822 and rs8124792. The control group consisted of 504 East Asians enrolled in the 1000 Genomes Project. Correlations between CYP24A1 SNPs and the diseases were analyzed by Fisher's exact probability *** CYP24A1 polymorphisms rs4809957 A/G and rs6068816 C/T showed a statistically significant association with risk of the three diseases,when both the genotypes and allele frequencies were considered. With regard to rs6091822 G/T,all three diseases were related to risk allele carriers(GT + TT) vs wild-type(GG),but the associations between the allele frequencies and the diseases were not significant. The risk of colonic polyps and colon cancer was related to the allele frequencies of rs8124792 G/A,and this association remained for genotype frequencies of this SNP. CONCLUSION Four SNPs are related to the risk of colonic polyps and colon cancer. G allele in rs6091822 G/T may play an anti-cancer role only if it is homozygous. The A allele,which is a minor component of rs8124792,may be indicated in the diagnosis of colonic polyps or colon cancer rather than ulcerative colitis.

关键词： CYP24A1 Single nucleotide polymorphisms Colonic polyps Colon cancer

Relationship between clinical features and intestinal microbiota in Chinese patients with ulcerative colitis

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World Journal of Gastroenterology 2021年第28期27卷 4722-4737页

作者： Xu-Xia He Ying-He li Peng-Guang Yan Xiang-Chen Meng Chu-Yan Chen Ke-Min li jing-nan li Department of Gastroenterology Peking Union Medical College HospitalPeking Union Medical College and Chinese Academy of Medical ScienceBeijing 100730China

BACKGROUND Dysbacteriosis may be a crucial environmental factor for ulcerative colitis(UC).Further study is required on microbiota alterations in the gastrointestinal tract of patients with UC for better clinical management and *** To analyze the relationship between different clinical features and the intestinal microbiota,including bacteria and fungi,in Chinese patients with *** Eligible inpatients were enrolled from January 1,2018 to June 30,2019,and stool and mucosa samples were *** was diagnosed by endoscopy,pathology,Mayo Score,and Montreal *** amplicon sequencing of 16S rRNA gene and fungal internal transcribed spacer gene was used to detect the intestinal microbiota *** diversity,principal component analysis,similarity analysis,and Metastats analysis were employed to evaluate differences among *** A total of 89 patients with UC and 33 non-inflammatory bowel disease(IBD)controls were *** bacterial analysis,72 stool and 48 mucosa samples were obtained from patients with UC and 21 stool and 12 mucosa samples were obtained from the *** fungal analysis,stool samples were obtained from 43 patients with UC and 15 controls.A significant difference existed between the fecal and mucosal bacteria of patients with ***α-diversity of intestinal bacteria and the relative abundance of some families,such as Lachnospiraceae and Ruminococcaceae,decreased with the increasing severity of bowel inflammation,while Escherichia-Shigella showed the opposite *** intermicrobial correlations in UC in remission than in active patients were *** bacteriafungi correlations became single and uneven in patients with *** The intestinal bacteria flora of patients with UC differs significantly in terms of various sample types and disease *** intermicrobial correlations change in patients with UC compared with non-IBD controls.

关键词： Ulcerative colitis Intestinal microbiota Intermicrobial correlation Bacteria Fungi Chinese

CYP24A1 Involvement in Inflammatory Factor Regulation Occurs via the Wnt Signaling Pathway

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Current Medical Science 2022年第5期42卷 1022-1032页

作者： Xue-qi CHEN Jia-yu MAO Chun-saier WANG Wen-bin li Tao-tao HAN Ke LV jing-nan li Department of Medical Ultrasound Peking Union Medical College HospitalPeking Union Medical College and Chinese Academy of Medical ScienceBeijing100730China Department of Critical Care Medicine Peking Union Medical College HospitalPeking Union Medical College and Chinese Academy of Medical ScienceBeijing100730China Department of Gastroenterology Beijing Friendship HospitalCapital Medical UniversityBeijing100050China Department of Gastroenterology Beijing HospitalNational Center of GerontologyInstitute of Geriatrics MedicineChinese Academy of Medical SciencesBeijing100730China Department of Gastroenterology Peking Union Medical College HospitalPeking Union Medical College and Chinese Academy of Medical Science Key Laboratory of Gut Microbiota Translational Medicine Research Chinese Academy of Medical ScienceBeijing100730China

Objective While the upregulation of cytochrome P450 family 24 subfamily A member 1(CYP24A1)gene expression has been reported in colon cancer,its role in tumorigenesis remains largely *** this study,we aimed to investigate the involvement of CYP24A1 in Wnt pathway regulation via the nuclear factor kappa B(NF-κB)*** The human colon cancer cell lines HCT-116 and Caco-2 were subjected to stimulation with interleukin-6(IL-6)as well as tumor necrosis factor alpha(TNF-α),with subsequent treatment using the NF-κB pathway-specific inhibitor ammonium pyrrolidinedithiocarbamate(PDTC).Furthermore,CYP24A1 expression was subjected to knockdown via the use of small interfering RNA(siRNA).Subsequently,NF-κB pathway activation was determined by an electrophoretic mobility shift assay,and the transcriptional activity ofβ-catenin was determined by a dual-luciferase reporter assay.A mouse ulcerative colitis(UC)-associated carcinogenesis model was established,wherein TNF-αand the NF-κB pathway were blocked by anti-TNF-αmonoclonal antibody and NF-κB antisense oligonucleotides,*** the tumor size and protein level of CYP24A1 were *** IL-6 and TNF-αupregulated CYP24A1 expression and activated the NF-κB pathway in colon cancer *** significantly inhibited this increase in CYP24A1 ***,knockdown of CYP24A1 expression by siRNA could partially antagonize Wnt pathway *** CYP24A1 expression was observed in the colonic epithelial cells of UC-associated carcinoma mouse ***-TNF-αmonoclonal antibody and NF-κB antisense oligonucleotides decreased the tumor size and suppressed CYP24A1 *** Taken together,this study suggests that inflammatory factors may increase CYP24A1 expression via NF-κB pathway activation,which in turn stimulates Wnt signaling.

关键词： CYP24A1 Wnt/β-catenin signaling pathway colorectal neoplasms

Gut hormones in microbiota-gut-brain cross-talk

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Chinese Medical Journal 2020年第7期133卷 826-833页

作者： li-Juan Sun jing-nan li Yong-Zhan Nie State Key Laboratory of Cancer Biology National Clinical Research Center for Digestive Diseases and Xijing Hospital of Digestive DiseasesThe Fourth Military Medical UniversityXi’anShaanxi 710032China Department of Clinical Nutrition Xijing HospitalThe Fourth Military Medical UniversityXi’anShaanxi 710032China Department of Gastroenterology Chinese Academy of Medical SciencesPeking Union Medical College HospitalBeijing 100730China

The homeostasis of the gut-brain axis has been shown to exert several effects on physiological and psychological *** gut hormones released by enteroendocrine cells scattered throughout the gastrointestinal tract are important signaling molecules within the gut-brain *** interaction between gut microbiota and gut hormones has been greatly appreciated in gut-brain *** microbiota plays an essential role in modulating many gut-brain axis-related diseases,ranging from gastrointestinal disorders to psychiatric ***,gut hormones also play pleiotropic and important roles in maintaining health,and are key signals involved in gut-brain *** importantly,gut microbiota can affect the release and functions of gut *** review highlights the role of gut microbiota in the gut-brain axis and focuses on how microbiota-related gut hormones modulate various physiological *** studies could target the microbiota-hormones-gut brain axis to develop novel therapeutics for different psychiatric and gastrointestinal disorders,such as obesity,anxiety,and depression.

关键词： Microbiota Gut hormones Gut-brain axis Appetite Anxiety Depression

Postoperative radiotherapy for thymus salivary gland carcinoma:A case report

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World Journal of Clinical Cases 2022年第26期10卷 9484-9492页

作者： Rui Deng nan-jing li liang-liang Bai Shi-Hong Nie Xiao-Wen Sun Yong-Sheng Wang Clinical Trial Center National Medical Products Administration Key Laboratory for Clinical Research and Evaluation of Innovative DrugsDepartment of Thoracic OncologyWest China HospitalSichuan UniversityCheng Du 610041Sichuan ProvinceChina Department of Radiation Oncology Cancer CenterWest China HospitalSichuan UniversityCheng Du 610041Sichuan ProvinceChina

BACKGROUND Salivary gland cancer is a rare disease in which cancer cells form in the tissues of the salivary *** mostly occurs in the glands that have secretion functions,such as the parotid gland,sublingual gland and submandibular *** is very rare when it occurs in other nonsecreting ***,we report one case of salivary gland carcinoma occurring in the thymus and discuss related diagnoses and treatment *** SUMMARY One 33-year-old middle-aged man presented with a thymus mass without any clinical symptoms when he underwent regular physical ***,the patient was admitted to the hospital for further *** tomography(CT)showed that there was a mass of 3 cm×2.8 cm×1.5 cm in the thymus *** patient had no symptom of discomfort or tumor-related medical history *** completing the preoperative examinations,it was confirmed that the patient had indications for *** surgeon performed a transthoracoscope"thymectomy+pleural mucostomy"for *** the operation,the tumor tissue was quickly frozen,and the symptomatic section showed a malignant *** final pathological result suggested thymus salivary gland carcinoma-mucoepidermoid carcinoma(MEC).In the second month after surgery,we performed local area radiotherapy for the patient,with a total radiation dose of 50.4 Gy/*** 12 mo of surgery,the patient underwent positron emission tomography-CT examination,which indicated that there was no sign of tumor recurrence or *** 16 mo of operation,CT scan re-examination showed that there was no sign of tumor recurrence or *** of the time of publication,the patient was followed up for one and a half *** had no sign of tumor recurrence and continued to *** The incidence of MEC in the thymus is low,and its diagnosis needs to be combined with clinical features and imaging *** analysis plays a key role in the diagnosis of the *** w

关键词： Thymic tumor Salivary gland carcinoma Mucoepidermoid carcinoma Postoperative Radiotherapy Case report

Insufficient awareness of celiac disease in China: population-based screening is needed

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Chinese Medical Journal 2019年第13期132卷 1513-1515页

作者： Chu-Yan Chen jing-nan li Department of Gastroenterology Key Laboratory of Gut Microbiota Translational Medicine ResearchPeking Union Medical College HospitalPeking Union Medical College Chinese Academy of Medical SciencesBeijing 100730China

Celiac disease (CD),once considered a gastrointestinal condition,is now known as a systemic autoimmune disease initiated by exposure to dietary gluten mainly in human leukocyte antigen DQ2 (HLA-DQ2) or HLA-DQ8 *** classic presentations of CD include intestinal manifestations such as chronic diarrhea,bloating,abdominal pain,constipation,weight loss,or poor growth in ***-deficiency,osteoporosis,and neuropathy attributable to vitamin B12 deficiency is also frequently seen in celiac *** responses spreading to tissues apart from the intestine cause dermatologic conditions such as dermatitis herpetiformis,and even increased risk of miscarriage in women.

关键词： celiac disease population-based screening miscarriage

Percutaneous aspiration and sclerotherapy of a giant simple hepatic cyst causing obstructive jaundice:A case report and review of literature

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World Journal of Gastrointestinal Surgery 2022年第7期14卷 706-713页

作者： Xu-Xia He Mei-Xing Sun Ke Lv Jian Cao Sheng-Yu Zhang jing-nan li Department of Gastroenterology Peking Union Medical College HospitalBeijing 10000China Department of Ultrasound Peking Union Medical College HospitalBeijing 10000China Department of Radiology Peking Union Medical College HospitalBeijing 10000China

BACKGROUND Giant simple hepatic cysts causing intrahepatic duct dilatation and obstructive jaundice are uncommon.A variety of measures with different clinical efficacies and invasiveness have been *** management,such as percutaneous aspiration and sclerotherapy,is often *** SUMMARY The case is a 39-year-old female with a 5-mo history of cutaneous and scleral icterus,loss of appetite,and dark *** tests showed jaundice and liver function *** revealed a giant simple hepatic cyst obstructing the intrahepatic bile ducts.A combination of percutaneous catheter aspiration and lauromacrogol sclerotherapy was successfully performed and the effects were satisfactory with the size of cyst decreasing from 13.7 cm×13.1 cm to 3.0 cm×3.0 *** literature review presented the challenges of managing giant simple hepatic cysts that cause obstructive jaundice and compared the safety and efficacy of a combination of percutaneous aspiration and lauromacrogol sclerotherapy with other management *** Giant simple hepatic cysts can cause obstructive jaundice,and a combination of percutaneous catheter aspiration and sclerotherapy with lauromacrogol are suggested to treat such cases.

关键词： Simple hepatic cyst Obstructive jaundice Aspiration Sclerotherapy Lauromacrogol Case report

C-reactive protein decreases interleukin-8 production in human endothelial progenitor cells by inhibition of p38 MAPK pathway

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Chinese Medical Journal 2009年第16期122卷 1922-1928页

作者： nan jing-long li Jian-jun HE Jian-guo Department of Cardiology Fu Wai Hospital Chinese Academy of Medical Sciences Peking Union Medical College Beijing 100037 China

Background C-reactive protein （CRP） has been reported to damage the vascular wall by inducing endothelial dysfunction and inflammation, and it is also speculated to have a role in attenuating angiogenic functions of human endothelial progenitor cells （EPCs）. Interleukin-8 （IL-8） is an important mediator of the paracrine mitogenic effect of EPCs which has direct angiogenic effects on mature endothelial cells. We, herein, investigated the direct effect of CRP on IL-8 production and gene expression in cultured human EPCs. Methods EPCs were isolated from the peripheral venous blood of healthy male volunteers. Cells were cultured in EndoCultTM liquid medium in the absence and presence of CRP at clinically relevant concentrations （5 to 25 μg/ml） for different durations （3 to 48 hours）. IL-8 protein and mRNA of cultured EPCs were evaluated using EliSA and real-time PCR. Results The results showed that CRP at a concentration of 10 μg/ml significantly reduced IL-8 secretion of cultured EPCs with a peak at 25 μg/ml, and also decreased mRNA expression in EPCs with a peak at 12 hours. In addition, preincubation of EPCs with SB203580, an inhibitor of p38 mitogen-activated protein kinase （MAPK） decreased CRP inhibition of IL-8 mRNA expression at 12 hours in EPCs. Conclusions Our study, for the first time, demonstrates that CRP directly inhibits EPCs IL-8 secretion, a key cytokine player of angiogenesis induced by EPCs. Inhibition occurred in part via an effect of CRP to active the p38 MAPK signal transduction pathway in EPC. The ability of CRP to inhibit EPCs IL-8 secretion may represent an important mechanism that further links inflammation to cardiovascular disease.

关键词： C-reactive protein endothelial progenitor cells interleukin-8