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Bile acids,gut microbiota,and therapeutic insights in hepatocellular carcinoma

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Cancer Biology & Medicine 2024年第2期21卷 144-162页

作者： Yang Song Harry CH Lau Xiang Zhang Jun Yu Institute of digestive Disease and department of Medicine and Therapeutics State Key Laboratory of Digestive DiseaseLi Ka Shing Institute of Health SciencesCUHK Shenzhen Research InstituteThe Chinese University of Hong KongHong KongChina department of Gastroenterology Zhongshan Hospital Xiamen UniversityXiamen 361004China

Hepatocellular carcinoma(HCC)is a prevalent and aggressive liver malignancy.The interplay between bile acids(BAs)and the gut microbiota has emerged as a critical factor in HCC development and progression.Under normal conditions,BA metabolism is tightly regulated through a bidirectional interplay between gut microorganisms and BAs.The gut microbiota plays a critical role in BA metabolism,and BAs are endogenous signaling molecules that help maintain liver and intestinal homeostasis.Of note,dysbiotic changes in the gut microbiota during pathogenesis and cancer development can disrupt BA homeostasis,thereby leading to liver inflammation and fibrosis,and ultimately contributing to HCC development.Therefore,understanding the intricate interplay between BAs and the gut microbiota is crucial for elucidating the mechanisms underlying hepatocarcinogenesis.In this review,we comprehensively explore the roles and functions of BA metabolism,with a focus on the interactions between BAs and gut microorganisms in HCC.Additionally,therapeutic strategies targeting BA metabolism and the gut microbiota are discussed,including the use of BA agonists/antagonists,probiotic/prebiotic and dietary interventions,fecal microbiota transplantation,and engineered bacteria.In summary,understanding the complex BA-microbiota crosstalk can provide valuable insights into HCC development and facilitate the development of innovative therapeutic approaches for liver malignancy.

关键词： Bile acid gut microbiota hepatocellular carcinoma therapeutics microbiota modulation

Alpha5 nicotine acetylcholine receptor subunit promotes intrahepatic cholangiocarcinoma metastasis

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Signal Transduction and Targeted Therapy 2024年第4期9卷 1690-1705页

作者： Yan Fu Keyu Shen Hao Wang Shun Wang Xufeng Wang Le Zhu Yan Zheng Tiantian Zou Hongfei Ci Qiongzhu Dong Lun-Xiu Qin Hepatobiliary surgery Department of General SurgeryHuashan Hospital&Cancer Metastasis InstituteFudan University200040 ShanghaiChina Center of Interventional Radiology and Vascular surgery Department of RadiologyZhongda HospitalMedical SchoolSoutheast University87 Dingjiaqiao Road210009 NanjingChina institutes of Biomedical Sciences Fudan University200032 ShanghaiChina Key Laboratory of Whole-period Monitoring and Precise Intervention of digestive Cancer Shanghai Municipal Health CommissionMinhang HospitalFudan UniversityShanghaiChina

Neurotransmitter-initiated signaling pathway were reported to play an important role in regulating the malignant phenotype of tumor cells.Cancer cells could exhibit a"neural addiction"property and build up local nerve networks to achieve an enhanced neurotransmitter-initiated signaling through nerve growth factor-mediated axonogenesis.Targeting the dysregulated nervous systems might represent a novel strategy for cancer treatment.However,whether intrahepatic cholangiocarcinoma(ICC)could build its own nerve networks and the role of neurotransmitters in the progression ICC remains largely unknown.Immunofluorescence staining and Enzyme-linked immunosorbent assay suggested that IcC cells and the infiltrated nerves could generate a tumor microenvironment rich in acetylcholine that promotes IcC metastasis by inducing epithelial-mesenchymal transition(EMT).Acetylcholine promoted iCC metastasis through interacting with its receptor,alpha 5 nicotine acetylcholine receptor subunits(CHRNA5).Furthermore,acetylcholine/CHRNA5 axis activated GSK3β/β-catenin signaling pathway partially through the influx of Ca^(2+)-mediated activation of Ca/calmodulin-dependent protein kinases(CAMKll).In addition,acetylcholine signaling activation also expanded nerve infiltration through increasing the expression of Brain-Derived Neurotrophic Factor(BDNF),which formed a feedforward acetylcholine-BDNF axis to promote ICC progression.KN93,a small-molecule inhibitor of CAMKIll,significantly inhibited the migration and enhanced the sensitivity to gemcitabine of ICC cells.Above all,Acetylcholine/CHRNA5 axis increased the expression ofβ-catenin to promote the metastasis and resistance to gemcitabine of ICC via CAMKIl/GSK3βsignaling,and the CAMKIl inhibitor KN93 may be an effective therapeutic strategy for combating ICC metastasis.

关键词： GSK3β metastasis Alpha

Human pangenome:far-reaching implications in precision medicine

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Frontiers of Medicine 2024年第2期18卷 403-409页

作者： Yingyan Yu Hongzhuan Chen department of General surgery of Ruijin Hospital Shanghai Institute of Digestive Surgeryand Shanghai Key Laboratory for Gastric NeoplasmsShanghai Jiao Tong University School of MedicineShanghai200025China Shuguang Lab for Future Health Shanghai Frontier Science Center of TCM Chemical BiologyShanghai University of Traditional Chinese MedicineShanghai201203China

Introduction.On May 11,2023,the internationally renowned journal Nature announced that a first draft of the human pangenome reference has been constructed[1].This research was carried out by the Human Pangenome Reference Consortium(HPRC).One month later,on June 14,2023,a pangenome reference of 36 Chinese populations was published on journal Nature[2],which was performed by Chinese Pangenome Consortium(CPC).As the scientists pointed out that since the Human Genome Project(HGP)published the human reference genome,it provided a reference blueprint for genomic research.However,the limitations of the human reference genome have gradually emerged,and it is difficult to reflect the genome diversity of the"human"species.

关键词： Human journal limitations

Bowel function and inflammation: Is motility the other side of the coin?

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World Journal of Gastroenterology 2024年第14期30卷 1963-1967页

作者： Alba Panarese Division of Gastroenterology and digestive Endoscopy Department of Medical SciencesCentral Hospital-Azienda OspedalieraTaranto 74123Italy

Digestion and intestinal absorption allow the body to sustain itself and are the emblematic functions of the bowel.On the flip side,functions also arise from its role as an interface with the environment.Indeed,the gut houses microorganisms,collectively known as the gut microbiota,which interact with the host,and is the site of complex immune activities.Its role in human pathology is complex and scientific evidence is progressively elucidating the functions of the gut,especially regarding the pathogenesis of chronic intestinal diseases and inflammatory conditions affecting various organs and systems.This editorial aims to highlight and relate the factors involved in the pathogenesis of intestinal and systemic inflammation.

关键词： Motility Inflammation Pathogenesis Vitamin D Microbiota Gut Chronic intestinal pseudo-obstruction

Close relationship between mediators of inflammation and pancreatic cancer:Our experience

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World Journal of Gastroenterology 2024年第23期30卷 2927-2930页

作者： Francesca Vescio Michele Ammendola Giuseppe Currò Silvia Curcio department General Surgery UnitUniversity“Magna Graecia”Medical SchoolUniversity Hospital“R.Dulbecco”Catanzaro 88100Italy Science of Health department Digestive Surgery UnitUniversity“Magna Graecia”Medical SchoolUniversity Hospital“R.Dulbecco”Catanzaro 88100Italy

In this editorial,we focus specifically on the mechanisms by which pancreatic inflammation affects pancreatic cancer.Cancer of the pancreas remains one of the deadliest cancer types.The highest incidence and mortality rates of pancreatic cancer are found in developed countries.Trends of pancreatic cancer incidence and mortality vary considerably worldwide.A better understanding of the etiology and identification of the risk factors is essential for the primary prevention of this disease.Pancreatic tumors are characterized by a complex microenvironment that orchestrates metabolic alterations and supports a milieu of interactions among various cell types within this niche.In this editorial,we highlight the foundational studies that have driven our understanding of these processes.In our experimental center,we have carefully studied the mechanisms of that link pancreatic inflammation and pancreatic cancer.We focused on the role of mast cells(MCs).MCs contain pro-angiogenic factors,including tryptase,that are associated with increased angiogenesis in various tumors.In this editorial,we address the role of MCs in angiogenesis in both pancreatic ductal adenocarcinoma tissue and adjacent normal tissue.The assessment includes the density of c-Kit receptor-positive MCs,the density of tryptase-positive MCs,the area of tryptasepositive MCs,and angiogenesis in terms of microvascularization density.

关键词： Mast cells C-Kit receptor Tryptase Angiogenesis Microvascular density Endothelial area Pancreatic tumor tissue Adjacent normal tissue

Radiation injury and gut microbiota-based treatment

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Protein & Cell 2024年第2期15卷 83-97页

作者： Weihong Wang Bota Cui Yongzhan Nie Lijuan Sun Faming Zhang department of Microbiota Medicine and Medical Center for digestive Diseases The Second Affiliated Hospital of Nanjing Medical UniversityNanjing210011China department of Microbiotherapy Sir Run Run HospitalNanjing Medical UniversityNanjing 211166China State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers and National Clinical Research Center for digestive Diseases Xijing Hospital of Digestive DiseasesFourth Military Medical UniversityXi'an 710032China National Clinical Research Center for digestive Diseases Xi'an 710032China Key Laboratory of Resource Biology and Biotechnology in Western China Ministry of EducationSchool of MedicineNorthwest UniversityXi'an 710069China

The exposure to either medical sources or accidental radiation can cause varying degrees of radiation injury(RI).RI is a common disease involving multiple human body parts and organs,yet effective treatments are currently limited.Accumulating evidence suggests gut microbiota are closely associated with the development and prevention of various RI.This article summarizes 10 common types of RI and their possible mechanisms.It also highlights the changes and potential microbiota-based treatments for RI,including probiotics,metabolites,and microbiota transplantation.Additionally,a 5P-Framework is proposed to provide a comprehensive strategy for managing RI.

关键词： microbiome ionizing radiation radiation-induced injury short-chain fatty acids fecal microbiota transplant washed microbiota transplantation war nuclear microbiota medicine

A comparative study of acupuncture combined with rehabilitation gymnastics on postoperative anal function of lower rectal cancer

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World Journal of Clinical Cases 2024年第18期12卷 3491-3496页

作者： Zhan-Lun Liu Yi-Wei He Yan-Feng Liu Ni Wang Wei Li Li-Zhong Shen department of digestive surgery Hebei Provincial Hospital of Traditional Chinese MedicineShijiazhuang 050000Hebei ProvinceChina

BACKGROUND From the anal function,inflammatory response and other indicators,acupuncture combined with rehabilitation gymnastics was applied to patients with cancer undergoing low resection,aiming to improve the prognosis of patients.AIM To explore the effects of acupuncture combined with rehabilitation gymnastics on anal function after lower rectal cancer surgery.METHODS From January 2020 to December 2022,128 patients who underwent rectal cancer surgery in the department of Oncology of Hebei Provincial Hospital of Traditional Chinese Medicine Hospital were selected and divided into two groups using the random number table method,with 64 patients in each group.Patients in the control group were not treated with acupuncture or rehabilitation gymnastics and served as blank controls.Patients in the study group were treated with acupuncture and rehabilitation gymnastics from the 7th postoperative day.The anal incontinence scores,changes in serum interleukin-4,interleukin-6,and interleukin-10 Levels,and serum motilin,5-hydroxytryptamine,and vasoactive intestinal peptide levels were compared.RESULTS There were no significant differences in serum interleukin-4,interleukin-6,and interleukin-10 Levels between the groups before treatment(P>0.05).After treatment,these levels were better than those of the control group(Psurgery(P>0.05).Anal incontinence scores in the study group were lower than those in the control group at 14 d,21 d,and 28 d postoperatively(P0.05).After treatment,these levels were higher in the study group than in the control group,and vasoactive intestinal peptide level was lower in the study group than in the control group(P<0.05).CONCLUSION Acupuncture combined with rehabilitation gymnastics can promote the recovery of anal function a

关键词： Low rectal cancer Anal function Acupuncture Rehabilitation gymnastics

Evaluating the clinical application and effect of acupuncture therapy in anal function rehabilitation after low-tension rectal cancer surgery

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World Journal of Clinical Cases 2024年第18期12卷 3476-3481页

作者： Li-Zhong Shen Wei Li Zhan-Lun Liu Ni Wang Yan-Feng Liu Ling-Ling Miao department of digestive surgery Hebei Province Hospital of Traditional Chinese MedicineShijiazhuang 050000Hebei ProvinceChina

BACKGROUND According to the indexes of serum and anal function,acupuncture therapy was applied to patients with low rectal cancer in order to avoid the occurrence of anal incontinence and reduce complications.AIM To explore the clinical application and evaluate the effect of acupuncture therapy for anal function rehabilitation after low-tension rectal cancer surgery.METHODS From the anorectal surgery cases,we selected 120 patients who underwent colorectal cancer surgery between January 2020 and December 2022 and randomly divided them into a control group(n=60),observation group(n=60),and control group after surgery for lifestyle intervention(including smoking cessation and exercise),dietary factor adjustment,anal movement,and oral loperamide treatment.The serum levels of motilin,5-hydroxytryptamine,and vasoactive intestinal peptide(VIP),Wexner score for anal incontinence,and incidence of complications were compared between groups.RESULTS After treatment,the VIP and 5-hydroxytryptamine levels in the observation group were lower than those in the control group(Psurgery;it can effectively help to improve the serum indices of patients,avoid the occurrence of anal incontinence,and reduce the incidence of complications.Popularizing and applying it will be valuable.

关键词： Acupuncture therapy Low pull rectal cancer Anal function rehabilitation Serum indicator Wexner score

Circ_0003855 involvement of esophageal cancer progression through miR-622/FLOT1

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Oncology Research 2024年第5期32卷 925-931页

作者： JINGJING TIAN XIBAO HU XINRONG ZHANG department of Gastroenterology Tianjin Nankai HospitalTianjin300100China department of digestive Medicine First Teaching Hospital of Tianjin University of Traditional Chinese MedicineTianjin300100China

To confirm the relationship between Circ_0003855 and EC,we purchased the Human esophageal carcinoma cell line Eca109 and normal human esophageal epithelial cells HEEC,and the expression levels of Circ_0003855,miR-622,and FLOT1 were detected.The results show that Circ_0003855 and FLOT1 were highly expressed in Eca109 cells,while miR-622 was lowly expressed(p0.05).Synthesizing the results of these experiments above,we believe that interfering with the expression of Circ_0003855 can inhibit the activity of EC cells,and its mechanism is related to miR-622 and FLOT1.

关键词： Circ_0003855 miR-622 FLOT1 Esophageal cancer Cell proliferation