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Managing type 2 diabetes:targeting a microbial enzyme as a novel treatment option

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Signal Transduction and Targeted Therapy 2024年第1期9卷 3-5页

作者： Anikó Keller-Pintér Tamás Korcsmáros Tibor Vellai department of Biochemistry Albert Szent-Györgyi Medical SchoolUniversity of SzegedSzeged6720Hungary department of Metabolism Digestion and ReproductionImperial College LondonLondonW120NNUK Quadram Institute Bioscience Norwich Research ParkNorwichNR47UQUK department of Genetics Eötvös Loránd University(ELTE)Budapest1117Hungary Hungarian Research Network HUN-REN-ELTE Genetics Research Group Budapest1117Hungary

In a recent Science article,Wang and colleagues showed that the dipeptidyl peptidase 4(DPP4)enzyme produced by the gut microbiota can interfere with the effect of host glucagon-like peptide-1(GLP-1)involved in stimulating insulin secretion,and the specific inhibitor of microbial DPP4(mDPP4),combined with clinical inhibitors of host DPP4 isoenzymes,further promotes blood glucose homeostasis.1 These results point out why certain patients respond inadequately to an antidiabetic medication.

关键词： homeostasis stimulating clinical

Antimicrobial stewardship and targeted therapies in the changing landscape of maternal sepsis

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Journal of Intensive Medicine 2024年第1期4卷 46-61页

作者： Nishel M Shah Esmita Charani Damien Ming Fook-Choe Cheah Mark R Johnson department of Metabolism Digestion and ReproductionImperial College LondonChelsea and Westminster HospitalLondonUK Health Protection Research Unit in Healthcare Associated Infection and Antimicrobial Resistance Imperial College LondonLondonUK Division of Infectious Diseases and HIV Medicine Department of MedicineGroote Schuur HospitalUniversity of Cape TownCape TownSouth Africa department of Infectious Diseases Imperial College LondonChelsea and Westminster HospitalLondonUK department of Paediatrics Faculty of MedicineUniversiti Kebangsaan Malaysia Medical CentreKuala LumpurMalaysia

Pregnant and postnatal women are a high-risk population particularly prone to rapid progression to sepsis with significant morbidity and mortality worldwide.Moreover,severe maternal infections can have a serious detrimental impact on neonates with almost 1 million neonatal deaths annually attributed to maternal infection or sepsis.In this review we discuss the susceptibility of pregnant women and their specific physiological and immunological adaptations that contribute to their vulnerability to sepsis,the implications for the neonate,as well as the issues with antimicrobial stewardship and the challenges this poses when attempting to reach a balance between clinical care and urgent treatment.Finally,we review advancements in the development of pregnancy-specific diagnostic and therapeutic approaches and how these can be used to optimize the care of pregnant women and neonates.

关键词： Sepsis Pregnancy Immunology Cardiovascular Personalised medicine Antibiotic stewardship

Uridine diphosphate glucuronosyltransferase 1A1 prevents the progression of liver injury

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World Journal of Gastroenterology 2024年第9期30卷 1189-1212页

作者： Jin-Lian Jiang Yi-Yang Zhou Wei-Wei Zhong Lin-Yan Luo Si-Ying Liu Xiao-Yu Xie Mao-Yuan Mu Zhi-Gang Jiang Yuan Xue Jian Zhang Yi-Huai He department of Infectious Diseases Affiliated Hospital of Zunyi Medical UniversityZunyi 563000Guizhou ProvinceChina department of Infectious Diseases Jingmen Central HospitalJingmen 448000Hubei ProvinceChina department of Respiratory Medicine Anshun People’s HospitalAnshun 561099Guizhou ProvinceChina department of General Practice Affiliated Hospital of Zunyi Medical UniversityZunyi 563000Guizhou ProvinceChina department of Intervention Radiology Affiliated Hospital of Zunyi Medical UniversityZunyi 563000Guizhou ProvinceChina School of Public Health Zunyi Medical UniversityZunyi 563099Guizhou ProvinceChina department of Liver Diseases Third People’s Hospital of ChangzhouChangzhou 213000Jiangsu ProvinceChina department of digestion Dafang County People’s HospitalBijie 551600Guizhou ProvinceChina

BACKGROUND Uridine diphosphate glucuronosyltransferase 1A1(UGT1A1)plays a crucial role in metabolizing and detoxifying endogenous and exogenous substances.However,its contribution to the progression of liver damage remains unclear.AIM To determine the role and mechanism of UGT1A1 in liver damage progression.METHODS We investigated the relationship between UGT1A1 expression and liver injury through clinical research.Additionally,the impact and mechanism of UGT1A1 on the progression of liver injury was analyzed through a mouse model study.RESULTS Patients with UGT1A1 gene mutations showed varying degrees of liver damage,while patients with acute-onchronic liver failure(ACLF)exhibited relatively reduced levels of UGT1A1 protein in the liver as compared to patients with chronic hepatitis.This suggests that low UGT1A1 levels may be associated with the progression of liver damage.In mouse models of liver injury induced by carbon tetrachloride(CCl_(4))and concanavalin A(ConA),the hepatic levels of UGT1A1 protein were found to be increased.In mice with lipopolysaccharide or liver steatosis-mediated liver-injury progression,the hepatic protein levels of UGT1A1 were decreased,which is consistent with the observations in patients with ACLF.UGT1A1 knockout exacerbated CCl_(4)-and ConA-induced liver injury,hepatocyte apoptosis and necroptosis in mice,intensified hepatocyte endoplasmic reticulum(ER)stress and oxidative stress,and disrupted lipid metabolism.CONCLUSION UGT1A1 is upregulated as a compensatory response during liver injury,and interference with this upregulation process may worsen liver injury.UGT1A1 reduces ER stress,oxidative stress,and lipid metabolism disorder,thereby mitigating hepatocyte apoptosis and necroptosis.

关键词： Uridine diphosphate glucuronosyltransferase 1A1 Liver injury progression Endoplasmic reticulum stress Oxidative stress Lipid metabolism disorders

Transcriptome analysis suggests broad jejunal alterations in Linghu’s obesity-diarrhea syndrome:A pilot study

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World Journal of Gastroenterology 2024年第21期30卷 2777-2792页

作者： Xiao-Tong Niu Xiang-Yao Wang Yan Wang Ke Han Nan Ru Jing-Yuan Xiang En-Qiang Linghu Medical School of Chinese PLA Chinese PLA General HospitalBeijing 100853China department of Gastroenterology The First Medical Center of Chinese PLA General HospitalBeijing 100853China School of Medicine Nankai UniversityTianjin 300071China

BACKGROUND Obesity is associated with a significantly increased risk for chronic diarrhea,which has been proposed as Linghu’s obesity-diarrhea syndrome(ODS);however,its molecular mechanisms are largely unknown.AIM To reveal the transcriptomic changes in the jejunum involved in ODS.METHODS In a cohort of 6 ODS patients(JOD group),6 obese people without diarrhea(JO group),and 6 healthy controls(JC group),high-throughput sequencing and bioinformatics analyses were performed to identify jejunal mucosal mRNA expression alterations and dysfunctional biological processes.In another cohort of 16 ODS patients(SOD group),16 obese people without diarrhea(SO group),and 16 healthy controls(SC group),serum diamine oxidase(DAO)and D-lactate(DLA)concentrations were detected to assess changes in intestinal barrier function.RESULTS The gene expression profiles of jejunal mucosa in the JO and JC groups were similar,with only 1 differentially expressed gene(DEG).The gene expression profile of the JOD group was significantly changed,with 411 DEGs compared with the JO group and 211 DEGs compared with the JC group,129 of which overlapped.The enrichment analysis of these DEGs showed that the biological processes such as digestion,absorption,and transport of nutrients(especially lipids)tended to be up-regulated in the JOD group,while the biological processes such as rRNA processing,mitochondrial translation,antimicrobial humoral response,DNA replication,and DNA repair tended to be down-regulated in the JOD group.Eight DEGs(CDT1,NHP2,EXOSC5,EPN3,NME1,REG3A,PLA2G2A,and PRSS2)may play a key regulatory role in the pathological process of ODS,and their expression levels were significantly decreased in ODS patients(P<0.001).In the second cohort,compared with healthy controls,the levels of serum intestinal barrier function markers(DAO and D-LA)were significantly increased in all obese individuals(P<0.01),but were higher in the SOD group than in the SO group(P<0.001).CONCLUSION Compared with healthy controls and obese individuals without diarrhe

关键词： Obesity Chronic diarrhea Jejunum Transcriptome Intestinal barrier

Analysis of quality of life in patients after transgastric natural orifice transluminal endoscopic gallbladder-preserving surgery

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World Journal of Gastrointestinal Endoscopy 2024年第6期16卷 318-325页

作者： Min-Yu Zhang Sen-Yuan Zheng Zheng-Yu Ru Zhi-Qiang Zhang department of Gastroenterology The First Affiliated Hospital of Xinjiang Medical UniversityUrimuqi 830011Xinjiang Uygur Autonomous RegionChina

BACKGROUND At present,laparoscopic cholecystectomy(LC)is the main surgical treatment for gallstones.But,after gallbladder removal,there are many complications.Therefore,it is hoped to remove stones while preserving the function of the gallbladder,and with the development of endoscopic technology,natural orifice transluminal endoscopic surgery came into being.AIM To compare the quality of life,perioperative indicators,adverse events after LC and transgastric natural orifice transluminal endoscopic gallbladder-preserving surgery(EGPS)in patients with gallstones.METHODS Patients who were admitted to The first Affiliated Hospital of Xinjiang Medical University from 2020 to 2022 were retrospectively collected.We adopted propen-sity score matching(1:1)to compare EGPS and LC patients.RESULTS A total of 662 cases were collected,of which 589 cases underwent LC,and 73 cases underwent EGPS.Propensity score matching was performed,and 40 patients were included in each of the groups.In the EGPS group,except the gastr-ointestinal defecation(P=0.603),the total score,physical well-being,mental well-being,and gastrointestinal digestion were statistically significant compared with the preoperative score after surgery(Pdigestion,the gastrointestinal defecation was statistically significant compared with the preoperative score after surgery(P<0.05).When comparing between groups,gastrointestinal defecation had significantly difference(P=0.002)between the two groups,there was no statistically significant difference in the total postoperative score and the other three subscales.In the surgery duration,hospital stay and cost,LC group were lower than EGPS group.The recurrence factors of gallstones after EGPS were analyzed:and recurrence was not correlated with gender,age,body mass index,number of stones,and preoperative score.CONCLUSION Whether EGPS or LC,it can improve the patient’s symptoms,and the EGPS has less impact on the patient

关键词： Gallstones Natural orifice transluminal endoscopic surgery Gallbladder preservation Cholecystolithotomy Laparoscopic cholecystectomy Gastrointestinal quality of life index

COMPARISON OF SHAMS' TEST FOR RECTAL MUCUS TO AN IMMUNOLOGICAL TEST FOR FECAL OCCULT BLOOD IN LARGE INTESTINAL CARCINOMA SCREENING ANALYSIS OF A CHECK-UP OF 6480 ASYMPTOMATIC SUBJECTS

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中华医学杂志(英文版) 1993年第10期106卷 739-742页

作者：周殿元冯福才张亚历赖卓胜张万岱李立波许国良万田漠潘德寿周丹张月彩李树彬 department of digestion Nanfang HospitalThe First Military Medical University

The sugar moiety detected from rectal mucus by the Galactose oxidase-schiff (Shams’ test) is considered a substitutive test for immunological fecal occult blood test (FOBT) in screening colorectal carcinoma. Two strategies of screening were applied in 6480 subjects over 40 years of age, and 130 cm flexible colonoscope used for sigmoidoscopy or pancolonoscopy. Of them, 3820 were taken for immune FOBT (SPA test) and Shams’ test. Only those who showed positive tests were chosen for 60 cm flexible sigmoidoscopy, while another 2660 subjects for both sigmoidoscopy and tests at the same time. Additionally, 130 cm flexible pancolonoscopy was carried out in 103 individuals with positive Shams’ test for evaluating the false positive rate. Shams’ test showed a sensitivity of 85.7% for colorectal cancer, 47.1% for adenomas in preselected patients, while the positive rate of SPA test were 90.5% and 41.2% respectively. In 3820 asymptomatic subjects undergoing sequential screening (aged 45 years and higher), Shams’ test showed 9.1% positive, SPA showed 11.2% and 620(16.2%) subjects were selected for sigmoidoscopy based on their positive galactose oxidase result or positive FOBT result. Two early stage carcinomas and 33 adenomas (0.32% and 4.2% respectively in sigmoidoscopy) were found. Another 2 660 subjects were taken for sigmoidoscopy screening. Four carcinomas and 78 adenomas were found. Of them, only two carcinoma (50%) and 17(21.8%) or 22(28.2%) adenomas were positive in Shams’ or SPA test. But both tests combined in screening showed a rate of 61.3% in adenomas and 75.0% in cancers. 103 subjects with positive Shams’ test were taken for pancolonoscopy. 82.5% showed no lesions. On these, we conclude that simple Shams’ test can be regarded as a complementary test for immunological FOBT in screening colorectal carcinomas.

关键词： COLORECTAL-CANCER

Treatment of a large area perioral viral herpes infection following noninvasive ventilation:A case report

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World Journal of Clinical Cases 2023年第8期11卷 1857-1861页

作者： A-Mao Tang Jia-Ying Xu Rong Wang Yi-Min Li department of digestion The Affiliated Hangzhou First People's HospitalZhejiang University School of MedicineHangzhou 310000Zhejiang ProvinceChina department of Nursing The Affiliated Hangzhou First People's HospitalZhejiang University School of MedicineHangzhou 310006Zhejiang ProvinceChina

BACKGROUND Alphaherpesvirus belongs to the Herpesviridae family and has large,monopartite double-stranded linear DNA.It mainly infects the skin,mucosa,and nerves,and can affect various hosts,including humans and other animals.Here,we present a case of a patient seen by the gastroenterology department at our hospital who experienced an oral and perioral herpes infection following treatment with a ven-tilator.The patient was treated with oral and topical antiviral drugs,furacilin,oral and topical antibiotics,local epinephrine injection,topical thrombin powder,and nutritional and supportive care.A wet wound healing approach was also implemented with good response.CASE SUMMARY A 73-year-old woman presented to the hospital with a chief complaint of"abdominal pain for 3 d with dizziness for 2 d."She was admitted to the intensive care unit for septic shock and spontaneous peritonitis secondary to cirrhosis and was given antiinflammatory and symptomatic supportive treatment.A ventilator was used to assist breathing for acute respiratory distress syndrome,which developed during her admission.A large area of herpes infection appeared in the perioral region 2 d following noninvasive ventilation.The patient was transferred to the gastroenterology department,at which time she had a body temperature of 37.8 C and a respiratory rate of 18/min.The patient's con-sciousness was intact,and she no longer had abdominal pain or distension,chest tightness,or asthma.At this point,the infected perioral region changed in appearance and was now accompanied by local bleeding with crusting of blood at the wounds.The surface area of the wounds measured approximately 10 cm×10 cm.A cluster blisters appeared on the patient’s right neck,and ulcers developed in her mouth.On a subjective numerical pain scale,the patient reported a pain level of 2.Overall,her diagnoses other than the oral and perioral herpes infection included:(1)Septic shock;(2)spontaneous peritonitis;(3)abdominal infection;(4)decompensated cirrhosis;and(5)hypoproteinemia.Dermatolo

关键词： Ventilator Viral herpes Nursing care Case report

Effects of sulfhydryl compounds on pancreatic cytoprotection in acute necrotic pancreatitis

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Chinese Medical Journal 2003年第1期116卷 57-61页

作者：崔培林杨昭徐张磊孙异临 department of digestion

Objective To observe sulfhydryl compound variation in the injury of pancreatic cells and the effects of external sulfhydryl compounds on cytoprotection.Methods Male Wistar mice were divided randomly into three groups: groups A and B served as animal models (retrograde duct infusion with 5% sodium taurocholate), in group A, 45 animals were treated with normal saline therapy, in group B, 45 aminals were treated with Tiopronin therapy; and group C, 15 animals, were designated as normal control. Animals were killed at 2, 4, 6, 12 and 24 h, and pancreatic tissue was analyzed for total sulfhydryl (TSH), nonprotein sulfhydryl (NPSH) and malondialdehyde (MDA). Histopathology, serum amylase (Sam) and C reactive protein (CRP) were assessed as well.Results Levels of Sam and CRP increased in both group A and group B, with corresponding pathological changes of acute nerotic pancreatitis (ANP). Levels of TSH, NPSH and protein sulfhydryl (PSH) in group A decreased markedly during pancreatitis (P<0.01), but MDA increased significantly (P<0.01). The depletion of NPSH in group B was markedly ameliorated at 4 h or 6 h, when Tiopronin was prophylactically administered (P<0.05), after which the level of MDA showed very little increase when compared to group A (P<0.01). Histopathological damage was attenuated to a certain extent, in regards to serum amylase and CRP.Conclusions All sulfhydryl compounds decreased significantly during ANP; external sulfhydryl compound could protect the pancreatic cells most likely as a type of scavengers of oxygen free radicals, which are critically involved in the pathophysiology of ANP. Sulfhydryl plays an important role in the action of pancreatic cytoprotection.

关键词： cytoprotection sulfhydryl compound acute necrotic pancreatitis Tiopronin

Success rate of current human-derived gastric cancer organoids establishment and influencing factors:A systematic review and meta-analysis

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World Journal of Gastrointestinal Oncology 2024年第4期16卷 1626-1646页

作者： Kai-Lin Jiang Xiang-Xiang Wang Xue-Jiao Liu Li-Kun Guo Yong-Qi Chen Qing-Ling Jia Ke-Ming Yang Jiang-Hong Ling department of Gastroenterology Shuguang HospitalShanghai 200021China department of Pathology Shuguang HospitalShanghai 200021China

BACKGROUND Human-derived gastric cancer organoids(GCOs)are widely used in gastric cancer research;however,the culture success rate is generally low.AIM To explore the potential influencing factors,and the literature on successful culture rates of GCOs was reviewed using meta-analysis.METHODS PubMed,Web of Science,and EMBASE were searched for studies.Two trained researchers selected the studies and extracted data.STATA 17.0 software was used for meta-analysis of the incidence of each outcome event.The adjusted Methodological Index for Non-Randomized Studies scale was used to assess the quality of the included studies.Funnel plots and Egger’s test were used to detect publication bias.Subgroup analyses were conducted for sex,tissue source,histo-logical classification,and the pathological tumor-node-metastasis(pTNM)cancer staging system.RESULTS Eight studies with a pooled success rate of 66.6%were included.GCOs derived from women and men had success rates of 67%and 46.7%,respectively.GCOs from surgery or biopsy/endoscopic submucosal dissection showed success rates of 70.9%and 53.7%,respectively.GCOs of poorly-differentiated,moderately-differentiated and signet-ring cell cancer showed success rates of 64.6%,31%,and 32.7%,respectively.GCOs with pTNM stages I-II and III-IV showed success rates of 38.3%and 65.2%,respectively.Y-27632 and non-Y-27632 use showed success rates of 58.2%and 70%,respectively.GCOs generated with collagenase were more successful than those constructed with Liberase TH and TrypLE(72.1%vs 71%,respectively).EDTA digestion showed a 50%lower success rate than other methods(P=0.04).CONCLUSION GCO establishment rate is low and varies by sex,tissue source,histological type,and pTNM stage.Omitting Y-27632,and using Liberase TH,TrypLE,or collagenase yields greater success than EDTA.

关键词： Gastric cancer organoids Human-derived organoids Gastric cancer Cell lines In vitro research models