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片仔癀通过调节小鼠的肠道菌群和代谢物抑制非酒精性脂肪性肝炎

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Engineering 2024年第4期35卷 257-269页

作者： Xianyi Zeng Xiang Zhang Hao Su Hongyan Gou harry cheuk-Hay lau Xiaoxu Hu Ziheng Huang Yan Li Jun Yu Shenzhen Research Institute The Chinese University of Hong KongShenzhen 518057China Department of Medicine and Therapeutics Institute of Digestive DiseaseState Key Laboratory of Digestive DiseaseLi Ka Shing Institute of Health SciencesThe Chinese University of Hong KongHong Kong 999077China

Non-alcoholic steatohepatitis(NASH)is a severe form of non-alcoholic fatty liver disease without effective *** traditional chinese medicine formulation Pien Tze Huang(PTH)can suppress inflammatory ***,we evaluate the effects of PTH on the evolution of NASH and its underlying *** found that PTH prevented the development of steatohepatitis induced by various dietary models,including a high-fat high-cholesterol(HFHC)diet,choline-deficient high-fat diet(CD-HFD),and methionine-and choline-deficient(MCD)diet,along with significant suppression of liver injury,hepatic triglyceride,and lipid ***,ten days of PTH treatment after the onset of NASH significantly ameliorated MCD diet-induced steatosis and liver injury in *** the metagenomic sequencing of stool samples,we found that PTH administration restored the gut microbiota with enrichment of probiotics including Lactobacillus acidophilus(***),Lactobacillus plantarum,Lactococcus lactis,and Bacillus *** enriched *** prevented MCD diet-induced *** addition,PTH restored the gut barrier function in mice with steatohepatitis,as evidenced by reduced intestinal permeability,decreased serum lipopolysaccharides(LPS)level,and increased epithelial tightjunction protein E-cadherin *** metabolomic analysis via liquid chromatography-mass spectrometry profiling identified the alteration in the metabolism of bile acids in the portal vein of PTHtreated *** further confirmed that an intact gut microbiota is necessary for PTH to exhibit antisteatohepatitis *** conclusion,PTH protects against steatohepatitis development by modulating the gut microbiota and *** is a potential promising prophylactic and therapeutic option for patients with NASH.

关键词： Pien Tze Huang Non-alcoholic steatohepatitis Gut barrier function Gut microbiota

Associating liver partition and portal vein ligation for staged hepatectomy： the current role and development

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Hepatobiliary & Pancreatic Diseases International 2017年第1期16卷 17-26页

作者： Wan Yee lau Eric ch Lai Stephanie HY lau Faculty of Medicine The Chinese University of Hong Kong Shatin New Territories Department of Surgery Pamela Youde Nethersole Eastern Hospital Department of Surgery Queen Elizabeth Hospital Hong Kong China

BACKGROUND： Associating liver partition and portal vein ligation for staged hepatectomy （ALPPS） has recently been developed to induce rapid liver hypertrophy and reduce posthepatectomy liver failure in patients with insufficient future liver remnant （FLR）. ALPPS is still considered to be in an early developmental phase because surgical indications and techniques have not been standardized. This article aimed to review the current role and future developments of ALPPS. DATA SOURCES： Studies were identified by searching MED- LINE and PubMed for articles from January 2007 to October 2016 using the keywords ＂associating liver partition and portal vein ligation for staged hepatectomy＂ and ＂ALPPS＂ Addi- tional papers were identified by a manual search of references from key articles. RESULTS： ALPPS induces more hypertrophy of the FLR in less time than portal vein embolization or portal vein ligation. The benefits of ALPPS include rapid hypertrophy 47%-110% of the liver over a median of 6-16.4 days, and 95%-100% com- pletion rate of the second stage of ALPPS. The main criticisms of ALPPS are centered on its high morbidity and mortality rates. Morbidity rates after ALPPS have been reported to be 15.3%-100%, with ≥ the Clavien-Dindo grade III morbidity of 13.6%-44%. Mortality rates have been reported to be 0%-29%. The important questions to ask even if oncologic long-term results are acceptable are： whether the gain in quality and quantity of life can be off balance by the substantial risks of morbidity and mortality, and whether stimulation of rapid liver hypertrophy also accelerates rapid tumor progression and spread. Up till now, the documentations of the ALPPS procedure come mainly from case series, and most of these series include heterogeneous groups of malignancies. The numbers are also too small to separately evaluate survival for different tumor etiologies. CONCLUSIONS： Currently, knowledge on ALPPS is limited, and prospective randomized studies are lacking. From th

关键词： associating liver partition and portal vein ligation for staged hepatectomy portal vein embolization laparoscopy colorectal liver metastases hepatocellular carcinoma

Gut microbiome alters functions of mutant p53 to promote tumorigenesis

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Signal Transduction and Targeted Therapy 2020年第1期5卷 491-492页

作者： harry cheuk Hay lau Jun Yu Institute of Digestive Disease Department of Medicine and TherapeuticsState Key Laboratory of Digestive DiseaseLi Ka Shing Institute of Health SciencesCUHK Shenzhen Research InstituteThe Chinese University of Hong KongSha TinN.T.Hong Kong

In a recent study in Nature,Kadosh et al.1 established a landmark relationship between the gut microbiome and host epigenetics in intestinal *** demonstrated the substantial plasticity of mutant p53 in WNT-driven tumo... 详细信息

关键词： tumorigenesis involvement al

Modifications of ALPPS–from complex to more complex or from complex to less complex operations

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Hepatobiliary & Pancreatic Diseases International 2017年第4期16卷 346-352页

作者： Wan Yee lau Eric ch Lai Faculty of Medicine The Chinese University of Hong KongShatinNew TerritoriesHong Kong SARChina Department of Surgery Pamela Youde Nethersole Eastern HospitalHong Kong SARChina

BACKGROUND: Associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) has recently been developed to induce rapid liver hypertrophy to reduce the chance of post-hepatectomy liver failure in patients with borderline or insufficient future liver remnant. ALPPS is still in an early developmental stage and its techniques have not been standardized. This study aimed to review the technical modifications of the conventional ALPPS procedure. DATA SOURCES: Studies were identified by searching MEDLINE and PubMed for articles published from January 2007 to December 2016 using the keywords 'associating liver partition and portal vein ligation for staged hepatectomy' and 'ALPPS'. Additional articles were identified by a manual search of references from key articles. RESULTS: There have been a lot of modifications of the conventional ALPPS. These are classified as: (1) modifications aiming to improve surgical results; (2) modifications aiming to expand surgical indications; (3) salvage ALPPS; (4) ALPPS using the minimally invasive approach. Some of these modifications have made the conventional ALPPS procedure to become even more complex, although there have also been other attempts to make the procedure less complex. The results of most of these modifications have been reported in small case series or case reports. We need better well-designed studies to establish the true roles of these modifications. However, it is interesting to see how this conventional ALPPS procedure has evolved since its introduction. CONCLUSIONS: There is a trend for the use of minimally invasive procedure in the phase 1 or 2 of the conventional ALPPS procedure. Some of these modifications have expanded the use of ALPPS in patients who have been considered to have unresectable liver tumors. The long-term oncological outcomes of these modifications are still unknown.

关键词： associating liver partition and portal vein ligation for stage hepatectomy hepatocellular carcinoma hepatectomy liver metastasis portal vein embolization

Hemodynamics and oxygen transport dynamics during hepatic resection at different central venous pressures in a pig model

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Hepatobiliary & Pancreatic Diseases International 2011年第5期10卷 516-520页

作者： Wan-Yee lau Eric ch Lai Department of Hepatic and Biliary Surgery First Affiliated Hospital Guangxi Medical University Faculty of Medicine the Chinese University of Hong Kong Shatin New Territories Hongkong SAR China

BACKGROUND: Although low central venous pressure (CVP) has been used to minimize blood loss during hepatectomy the impact of variations of CVP on the rate of blood loss and on the perfusion of end-organs has not been evaluated This animal study aimed to evaluate the hemodynamics and oxygen transport changes during hepatic resection at different CVP levels. METHODS: Forty-eight anesthetized Bama miniature pigs were divided into 8 groups with CVP during hepatic resection controlled at 0 to <1, 1 to <2, 2 to <3, 3 to <4, 4 to <5, 5 to <6, 6 to <7, and 7 to <8 cmH 2 O. Intergroup comparisons were made for hemodynamic parameters, oxygen transport dynamics, and the rate of blood loss. RESULTS: The rate of blood loss and the hepatic venous pressure during hepatic resection were almost linearly related to the CVP. A significant drop in the mean arterial pressure cardiac output, and cardiac index occurred between CVP ≥2 and <2 cmH 2 O. Oxygen delivery (DO 2 ), oxygen consumption (VO 2 ) and oxygen extraction ratio (ERO 2 ) remained relatively constant between CVPs of 2 to <8 cmH 2 O. There was a significant drop in DO 2 when the CVP was <2 cmH 2 O. There was also a significant drop in VO 2 and ExO 2 when the CVP was <1 cmH 2 ***: The optimal CVP for hepatic resection is 2to 3 cmH2O.

关键词： hepatectomy hemorrhage central venous pressure tissue oxygenation hemodynamics

Microbiota-mediated phytate metabolism activates HDAC3 to contribute intestinal homeostasis

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Signal Transduction and Targeted Therapy 2020年第1期5卷 747-748页

作者： Xiaoxing Li harry cheuk Hay lau Jun Yu Institute of Precision Medicine First Affiliated HospitalSun Yat-Sen UniversityGuangzhouChina Institute of Digestive Disease Department of Medicine and TherapeuticsState Key Laboratory of Digestive DiseaseLi Ka Shing Institute of Health SciencesCUHK Shenzhen Research InstituteThe Chinese University of Hong KongSha TinNewTerritoriesHong Kong

In a recent study in Nature,Wu et *** a fundamental host–microbe interaction that is crucially involved in responding to dietary change thereby maintaining healthy intestinal dynamics.1 They demonstrated that HDAC3 a... 详细信息

关键词： metabolism HDAC3 homeostasis

Gut Microbiome in Colorectal Cancer:Clinical Diagnosis and Treatment

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Genomics, Proteomics & Bioinformatics 2023年第1期21卷 84-96页

作者： Yali Liu harry cheuk-Hay lau Wing Yin cheng Jun Yu Institute of Digestive Disease and The 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 Kong Special Administrative Region 999077China

Colorectal cancer(CRC)is one of the most frequently diagnosed cancers and the leading cause of cancer-associated *** studies have shown that both genetic and environmental risk factors contribute to the development of *** metagenomic studies of CRC have identified gut dysbiosis as a fundamental risk factor in the evolution of colorectal *** enormous efforts and substantial progresses have been made in understanding the relationship between human gut microbiome and CRC,the precise mechanisms involved remain *** data have shown a direct causative role of the gut microbiome in DNA damage,inflammation,and drug resistance in CRC,suggesting that modulation of gut microbiome could act as a powerful tool in CRC prevention and ***,we provide an overview of the relationship between gut microbiome and CRC,and explore relevant mechanisms of colorectal *** next highlight the potential of bacterial species as clinical biomarkers,as well as their roles in therapeutic *** limiting the clinical translation of gut microbiome and strategies for resolving current challenges are further discussed.

关键词： Gut microbiome Colorectal cancer Diagnostic biomarker Immunotherapy chemotherapy

Uncovering novel human gut virome using ultra-deep metagenomic sequencing

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chinese Medical Journal 2022年第20期135卷 2395-2397页

作者： harry cheuk Hay lau Jun Yu Institute of Digestive Disease and Department of Medicine and Therapeutics State Key Laboratory of Digestive DiseaseLi Ka Shing Institute of Health Sciencesthe Chinese University of Hong KongHong Kong SARChina

Human gastrointestinal tract harbors trillions of commensal microbes including bacteria,viruses,and fungi to form an ecological community,commonly known as the gut *** the second most dominant taxonomic kingdom in the gut(5.8%of total microbiome DNA),enteric viruses are increasingly acknowledged for their roles in shaping the overall composition of the gut microbiome and maintaining human health.[1,2]Recent advancements in metagenomic sequencing have brought breakthrough in deciphering the features and functions of the gut virome.

关键词： breakthrough harbor gut

Identification of optimal contemporary antiemetic prophylaxis for doxorubicin-cyclophosphamide chemotherapy in chinese cancer patients: post-hoc analysis of 3 prospective studies

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Cancer Biology & Medicine 2021年第3期18卷 825-832页

作者： Winnie Yeo Leung Li Thomas KH lau Kwai T Lai Vicky,TC chan Kwan H Wong christopher ch Yip Elizabeth Pang Maggie cheung Vivian chan Carol ch Kwok Joyce JS Suen Frankie KF Mo Department of Clinical Oncology Prince of Wales HospitalFaculty of MedicineHong Kong Cancer InstituteHong KongChina State Key Laboratory of Translational Oncology The Chinese University of Hong KongHong KongChina Department of Clinical Oncology Princess Margaret HospitalHong KongChina

Objective:chemotherapy-induced nausea and vomiting(CINV)are common with doxorubicin-cyclophosphamide(AC)*** antiemetic regimens incorporate neurokinin-1 receptor antagonist(NK1 RA),5-hydroxytryptamine type-3 receptor antagonist(5 HT3 RA),corticosteroid,and dopamine *** post-hoc analysis compared results of 3 prospective antiemetic studies conducted among chinese breast cancer patients who received(neo)adjuvant AC,in order to identify optimal antiemetic ***:A total of 304 patients were included:Group 1,ondansetron/dexamethasone(D1);Group 2,aprepitant/ondansetron/dexamethasone(D1);Group 3,aprepitant/ondansetron/dexamethasone(D1–3);Group 4,aprepitant/ondansetron/dexamethasone(D1–3)/olanzapine;and Group 5,netupitant/palonosetron/dexamethasone(D1–3).Antiemetic efficacies of Groups 3,4,and 5 during cycle 1 of AC were individually compared with Group *** addition,emesis outcomes of patients in Groups 3 and 5,and those of Groups 2 and 3,were ***:When comparing efficacies of a historical doublet(5 HT3 RA/dexamethasone)with triplet antiemetic regimens(NK1 RA/5 HT3 RA/dexamethasone)with/without olanzapine,complete response(CR)percentages and quality of life(QOL)in overall phase of cycle 1 AC were compared between Group 1 and the other groups:Group 1 vs.3,41.9%vs.38.3%(P=0.6849);Group 1 vs.4,41.9%vs.65.0%(P=0.0107);and Group 1 vs.5,41.9%vs.60.0%(P=0.0460).Groups 4 and 5 achieved a better *** comparing netupitant-based(Group 3)with aprepitant-based(Group 5)triplet antiemetics,CR percentages were 38.3%vs.60.0%,respectively(P=0.0176);Group 5 achieved a better *** comparing 1 day(Group 2)vs.3 day(Group 3)dexamethasone,CR percentages were 46.8%and 38.3%,respectively(P=0.3459);Group 3 had a worse ***:Aprepitant-containing triplets were non-superior to doublet ***-containing triplets and adding olanzapine to aprepitant-containing triplets were superior to ***/palono

关键词： Netupitant palonosetron aprepitant olanzapine NEPA Asians