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 ...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.展开更多
Purpose:The aim of the current study was to investigate the association of accelerometer-measured sleep duration and different intensities of physical activity(PA)with the risk of incident type 2 diabetes in a populat...Purpose:The aim of the current study was to investigate the association of accelerometer-measured sleep duration and different intensities of physical activity(PA)with the risk of incident type 2 diabetes in a population-based prospective cohort study.Methods:Altogether,88,000 participants(mean age=62.2±7.9 years,mean±SD)were included from the UK Biobank.Sleep duration(short:<6 h/day;normal:6-8 h/day;long:>8 h/day)and PA of different intensities were measured using a wrist-won accelerometer over a 7-day period between 2013 and 2015.PA was classified according to the median or World Health Organization-recommendation:total volume of PA(high,low),moderate-to-vigorous PA(MVPA)(recommended,not recommended),and light-intensity PA(high,low).Incidence of type 2diabetes was ascertained using hospital records or death registries.Results:During a median follow-up of 7.0 years,1615 incident type 2 diabetes cases were documented.Compared with normal sleep duration,short(hazard ratio(HR)=1.21,95%confidence interval(95%CI):1.03-1.41)but not long sleep duration(HR=1.01,95%CI:0.89-1.15)was associated with excessive type 2 diabetes risk.This increased risk among short sleepers seems to be protected against by PA.Compared with normal sleepers with high or recommended PA,short sleepers with low volume of PA(HR=1.81,95%CI:1.46-2.25),not recommended(below the World Health Organization-recommended level of)MVPA(HR=1.92,95%CI:1.55-2.36),or low light-intensity PA(HR=1.49,95%CI:1.13-1.90)had a higher risk of type 2 diabetes,while short sleepers with a high volume of PA(HR=1.14,95%CI:0.88-1.49),recommended MVPA(HR=1.02,95%CI:0.71-1.48),or high light-intensity PA(HR=1.14,95%CI:0.92-1.41)did not.Conclusion:Accelerometer-measured short but not long sleep duration was associated with a higher risk of incident type 2 diabetes.A higher level of PA,regardless of intensity,potentially ameliorates this excessive risk.展开更多
Background:Nonalcoholic fatty liver disease(NAFLD)is associated with impaired renal function,and both diseases often occur alongside other metabolic disorders.However,the prevalence and risk factors for impaired renal...Background:Nonalcoholic fatty liver disease(NAFLD)is associated with impaired renal function,and both diseases often occur alongside other metabolic disorders.However,the prevalence and risk factors for impaired renal function in patients with NAFLD remain unclear.The objective of this study was to identify the prevalence and risk factors for renal impairment in NAFLD patients.Methods:All adults aged 18-70 years with ultrasound-diagnosed NAFLD and transient elastography examination from eight Asian centers were enrolled in this prospective study.Liver fibrosis and cirrhosis were assessed by FibroScan-aspartate aminotransferase(FAST),Agile 3+and Agile 4 scores.Impaired renal function and chronic kidney disease(CKD)were defined by an estimated glomerular filtration rate(eGFR)with value of<90 mL/min/1.73 m^(2) and<60 mL/min/1.73 m^(2),respectively,as estimated by the CKD-Epidemiology Collaboration(CKD-EPI)equation.Results:Among 529 included NAFLD patients,the prevalence rates of impaired renal function and CKD were 37.4%and 4.9%,respectively.In multivariate analysis,a moderate-high risk of advanced liver fibrosis and cirrhosis according to Agile 3+and Agile 4 scores were independent risk factors for CKD(P<0.05).Furthermore,increased fasting plasma glucose(FPG)and blood pressure were significantly associated with impaired renal function after controlling for the other components of metabolic syndrome(P<0.05).Compared with patients with normoglycemia,those with prediabetes[FPG≥5.6 mmol/L or hemoglobin A1c(HbA1c)≥5.7%]were more likely to have impaired renal function(P<0.05).Conclusions:Agile 3+and Agile 4 are reliable for identifying NAFLD patients with high risk of CKD.Early glycemic control in the prediabetic stage might have a potential renoprotective role in these patients.展开更多
Hepatitis due to hepatitis B virus(HBV)reactivation can be serious and potentially fatal,but is preventable.HBV reactivation is most commonly reported in patients receiving chemotherapy,especially rituximab-containing...Hepatitis due to hepatitis B virus(HBV)reactivation can be serious and potentially fatal,but is preventable.HBV reactivation is most commonly reported in patients receiving chemotherapy,especially rituximab-containing therapy for hematological malignancies and those receiving stem cell transplantation.Patients with inactive and even resolved HBV infection still have persistence of HBV genomes in the liver.The expression of these silent genomes is controlled by the immune system.Suppression or ablation of immune cells,most importantly B cells,may lead to reactivation of seemingly resolved HBV infection.Thus,all patients with hematological malignancies receiving anticancer therapy should be screened for active or resolved HBV infection by blood tests for hepatitis B surface antigen(HBsAg)and antibody to hepatitis B core antigen.Patients found to be positive for HBsAg should be given prophylactic antiviral therapy.For patients with resolved HBV infection,there are two approaches.The first is pre-emptive therapy guided by serial HBV DNA monitoring,and treatment with antiviral therapy as soon as HBV DNA becomes detectable.The second approach is prophy-lactic antiviral therapy,particularly for patients receiving high-risk therapy,especially anti-CD20 monoclonal antibody or hematopoietic stem cell transplantation.Entecavir and tenofovir are the preferred antiviral choices.Many new effective therapies for hematological malignancies have been introduced in the past decade,for example,chimeric antigen receptor(CAR)-T cell therapy,novel monoclonal antibodies,bispecific antibody drug conjugates,and small molecule inhibitors,which may be associated with HBV reactivation.Although there is limited evidence to guide the optimal preventive measures,we recommend antivi-ral prophylaxis in HBsAg-positive patients receiving novel treatments,including Bruton’s tyrosine kinase inhibitors,B-cell lymphoma 2 inhibitors,and CAR-T cell therapy.Further studies are needed to determine the risk of HBV reactivation with these agents and the best prophylactic strategy.展开更多
With advances in targeted and personalized treatment for lung cancer, molecular analysis of tumors is routinely performed for sequencing of treatment options in patients with advanced non-small-cell lung cancer (NSCLC...With advances in targeted and personalized treatment for lung cancer, molecular analysis of tumors is routinely performed for sequencing of treatment options in patients with advanced non-small-cell lung cancer (NSCLC). Oncogene addiction due to driver mutations includes EGFR exon 20 insertion mutations, MET amplification, EML4-AL, KRAS G12C point mutations, RET rearrangements, HER2 amplification and mutations, and FGFR amplification and translocations. A re-biopsy at the time of tumor recurrence or progression after first-line treatment failure is important for further molecular assessment and personalized therapy. However, repeat tumor biopsies are fraught with challenges including access to the tumor, sample inadequacy, patient consent, patient performance status, safety, or physician’s choice or assessment. Cytological specimens are gaining importance but are limited due to validation difficulties. Liquid biopsies, which are minimally invasive have shown promise to assess dynamic biomarkers using ctDNA analysis and are thus frequently considered in routine clinical practice in advanced NSCLC patients to guide further targeted treatment. Here we present a comprehensive review that emphasizes the significance of performing tumor re-biopsy in advanced stage NSCLC patients following resistance to first-line treatment and simultaneously highlights the current challenges in performing the same and the current status and future perspectives of liquid biopsy in NSCLC.展开更多
The overall incidence and burden caused by breast cancer is increasing,affecting the global socio-economic development and life expectancy[1].According to“WHO Global Breast Cancer Initiative(GBCI)reports”,if the mor...The overall incidence and burden caused by breast cancer is increasing,affecting the global socio-economic development and life expectancy[1].According to“WHO Global Breast Cancer Initiative(GBCI)reports”,if the mortality rate due to breast cancer can be reduced by 2.4%annually,we may prevent 2.5 million breast cancer deaths between2020-2040.展开更多
Emerging evidence suggests that microbial dysbiosis plays vital roles in many human cancers.However,knowledge of whether the microbial community in thyroid tumor is related to tumorigenesis remains elusive.In this stu...Emerging evidence suggests that microbial dysbiosis plays vital roles in many human cancers.However,knowledge of whether the microbial community in thyroid tumor is related to tumorigenesis remains elusive.In this study,we aimed to explore the microbial community in thyroid tissues and its contribution to papillary thyroid cancer(PTC).In parallel,we performed microbial profiling and transcriptome sequencing in the tumor and adjacent normal tissues of a large cohort of 340 PTC and benign thyroid nodule(BTN)patients.Distinct microbial signatures were identified in PTC,BTN,and their adjacent nontumor tissues.Intra-thyroid tissue bacteria were verified by means of bacteria staining,fluorescence in situ hybridization,and immunoelectron microscopy.We found that 17 bacterial taxa were differentially abundant in PTC compared with BTN,which included enrichment in PTC of the pathobionts Rhodococcus,Neisseria,Streptococcus,Halomonas,and Devosia,and depletion of the beneficial bacteria Amycolatopsis.These differentially abundant bacteria could differentiate PTC tumor tissues(PTC-T)from BTN tissues(BTN-T)with an area under the curve(AUC)of 81.66%.Microbial network analysis showed increased correlation strengths among the bacterial taxa in PTC-T in comparison with BTN-T.Immunefunction-corresponding bacteria(i.e.,Erwinia,Bacillus,and Acinetobacter)were found to be enriched in PTC with Hashimoto’s thyroiditis.Moreover,our integrative analysis revealed that the PTC-enriched bacteria had a positive association with key PTC-oncogenic pathway-related genes,including BRAF,KRAS,IRAK4,CTNNB1,PIK3CA,MAP3K7,and EGFR.In conclusion,our results suggest that intratumor bacteria dysbiosis is associated with the thyroid tumorigenesis and oncogenic signaling pathways of PTC.展开更多
Non-alcoholic steatohepatitis(NASH)is a severe form of non-alcoholic fatty liver disease without effective treatment.The traditional Chinese medicine formulation Pien Tze Huang(PTH)can suppress inflammatory diseases.H...Non-alcoholic steatohepatitis(NASH)is a severe form of non-alcoholic fatty liver disease without effective treatment.The traditional Chinese medicine formulation Pien Tze Huang(PTH)can suppress inflammatory diseases.Here,we evaluate the effects of PTH on the evolution of NASH and its underlying mechanisms.We 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 peroxidation.Moreover,ten days of PTH treatment after the onset of NASH significantly ameliorated MCD diet-induced steatosis and liver injury in mice.Through the metagenomic sequencing of stool samples,we found that PTH administration restored the gut microbiota with enrichment of probiotics including Lactobacillus acidophilus(L.acidophilus),Lactobacillus plantarum,Lactococcus lactis,and Bacillus subtilis.The enriched L.acidophilus prevented MCD diet-induced steatohepatitis.In 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 expression.Our metabolomic analysis via liquid chromatography-mass spectrometry profiling identified the alteration in the metabolism of bile acids in the portal vein of PTHtreated mice.We further confirmed that an intact gut microbiota is necessary for PTH to exhibit antisteatohepatitis effects.In conclusion,PTH protects against steatohepatitis development by modulating the gut microbiota and metabolites.PTH is a potential promising prophylactic and therapeutic option for patients with NASH.展开更多
Precise chemical cue presentation alongside advanced brainwide imaging techniques is important to the study of chemosensory processing in animals.Nevertheless,the dynamic nature of chemical-carrying media,such as wate...Precise chemical cue presentation alongside advanced brainwide imaging techniques is important to the study of chemosensory processing in animals.Nevertheless,the dynamic nature of chemical-carrying media,such as water or air,poses a significant challenge for delivering highly-controlled chemical flow to an animal subject.Moreover,contact-based cue manipulation and delivery easily shift the position of the animal subject,which is often undesirable for high-quality brain imaging.Additionally,more advanced interfacing tools that align with the diverse range of body part sizes of an animal,ranging from micrometer-scale neurons to meter-long limbs,are much needed.This is particularly crucial when dealing with dimensions that are beyond the reach of conventional experimental tools.展开更多
The complement system plays a crucial role in the innate defense against common pathogens. Activation of complement leads to robust and efficient proteolytic cascades, which terminate in opsonization and lysis of the ...The complement system plays a crucial role in the innate defense against common pathogens. Activation of complement leads to robust and efficient proteolytic cascades, which terminate in opsonization and lysis of the pathogen as well as in the generation of the classical inflammatory response through the production of potent proinflammatory molecules. More recently, however, the role of complement in the immune response has been expanded due to observations that link complement activation to adaptive immune responses. It is now appreciated that complement is a functional bridge between innate and adaptive immune responses that allows an integrated host defense to pathogenic challenges. As such, a study of its functions allows insight into the molecular underpinnings of host-pathogen interactions as well as the organization and orchestration of the host immune response. This review attempts to summarize the roles that complement plays in both innate and adaptive immune responses and the consequences of these interactions on host defense.展开更多
Gastric cancer remains a global killer with a shifting burden from the developed to the developing world. The cancer develops along a multistage process that is defined by distinct histological and pathophysiological ...Gastric cancer remains a global killer with a shifting burden from the developed to the developing world. The cancer develops along a multistage process that is defined by distinct histological and pathophysiological phases. Several genetic and epigenetic alterations mediate the transition from one stage to another and these include mutations in oncogenes, tumour suppressor genes and cell cycle and mismatch repair genes. The most significant advance in the fight against gastric caner came with the recognition of the role of Helicobacter pylori （H pylori） as the most important acquired aetiological agent for this cancer. Recent work has focussed on elucidating the complex host/microbial interactions that underlie the neoplastic process. There is now considerable insight into the pathogenesis of this cancer and the prospect of preventing and eradicating the disease has become a reality. Perhaps more importantly, the study of H pylori-induced gastric carcinogenesis offers a paradigm for understanding more complex human cancers. In this review, we examine the molecular and cellular events that underlie Hpyloriinduced gastric cancer.展开更多
Chronic hepatitis B(CHB)virus infection is a global public health problem,affecting more than 400 million people worldwide.The clinical spectrum is wide,ranging from a subclinical inactive carrier state,to progressive...Chronic hepatitis B(CHB)virus infection is a global public health problem,affecting more than 400 million people worldwide.The clinical spectrum is wide,ranging from a subclinical inactive carrier state,to progressive chronic hepatitis,cirrhosis,decompensation,and hepatocellular carcinoma.However,complications of hepatitis B virus(HBV)-related chronic liver disease may be reduced by viral suppression.Current international guidelines recommend first-line treatment of CHB infection with pegylated interferon,entecavir,or tenofovir,but the optimal treatment for an individualpatient is controversial.The indications for treatment are contentious,and increasing evidence suggests that HBV genotyping,as well as serial on-treatment measurements of hepatitis B surface antigen and HBV DNA kinetics should be used to predict antiviral treatment response.The likelihood of achieving a sustained virological response is also increased by extending treatment duration,and using combination therapy.Hence the paradigm for treatment of CHB is constantly evolving.This article summarizes the different indications for treatment,and systematically reviews the evidence for the efficacy of various antiviral agents.It further discusses the shortcomings of current guidelines,use of rescue therapy in drug-resistant strains of HBV,and highlights the promising clinical trials for emerging therapies in the pipeline.This concise overview presents an updated practical approach to guide the clinical management of CHB.展开更多
Hepatitis due to hepatitis B virus(HBV) reactivation can be severe and potentially fatal, but is preventable. HBV reactivation is most commonly reported in patients receiving cancer chemotherapy, especially rituximabc...Hepatitis due to hepatitis B virus(HBV) reactivation can be severe and potentially fatal, but is preventable. HBV reactivation is most commonly reported in patients receiving cancer chemotherapy, especially rituximabcontaining therapy for hematological malignancies and those receiving stem cell transplantation. All patients with hematological malignancies receiving anticancer therapy should be screened for active or resolved HBV infection by blood tests for hepatitis B surface antigen(HBs Ag) and antibody to hepatitis B core antigen(antiHBc). Patients found to be positive for HBs Ag should be given prophylactic antiviral therapy to prevent HBV reactivation. For patients with resolved HBV infection, no standard strategy has yet been established to prevent HBV reactivation. There are usually two options. One is pre-emptive therapy guided by serial HBV DNA monitoring, whereby antiviral therapy is given as soon as HBV DNA becomes detectable. However, there is little evidence regarding the optimal interval and period of monitoring. An alternative approach is prophylactic antiviral therapy, especially for patients receiving highrisk therapy such as rituximab, newer generation of anti-CD20 monoclonal antibody, obinutuzumab or hematopoietic stem cell transplantation. This strategy may effectively prevent HBV reactivation and avoid the inconvenience of repeated HBV DNA monitoring. Entecavir or tenofovir are preferred over lamivudine as prophylactic therapy. Although there is no well-defined guideline on the optimal duration of prophylactic therapy, there is growing evidence to recommend continuing prophylactic antiviral therapy for at least 12 mo after cessation of chemotherapy, and even longer for those who receive rituximab or who had high serum HBV DNA levels before the start of immunosuppressive therapy. Many novel agents have recently become available for the treatment of hematological malignancies, and these agents may be associated with HBV reactivation. Although there is currently limited evidence to guide the optimal preventive measures, we recommend antiviral prophylaxis in HBs Ag-positive patients receiving novel treatments, especially the Bruton tyrosine kinase inhibitors and the phosphatidylinositol 3-kinase inhibitors, which are B-cell receptor signaling modulators and reduce proliferation of malignant B-cells. Further studies are needed to clarify the risk of HBV reactivation with these agents and the best prophylactic strategy in the era of targeted therapy for hematological malignancies.展开更多
AIM:To study serological antibodies in Caucasians and Asians,in health and inflammatory bowel disease(IBD),in Australia and Hong Kong(HK).METHODS:Anti-glycan antibodies[anti-chitobioside(ACCA),anti-laminaribioside(ALC...AIM:To study serological antibodies in Caucasians and Asians,in health and inflammatory bowel disease(IBD),in Australia and Hong Kong(HK).METHODS:Anti-glycan antibodies[anti-chitobioside(ACCA),anti-laminaribioside(ALCA)],and anti-mannobioside(AMCA),anti-Saccharomyces cervisiae(gASCA);and atypical perinuclear anti-neutrophil cytoplasmic antibody(pANCA)were tested in IBD patients,their unaffected relatives,and healthy controls in Australia and HK(China).Antibody status(positive or negative)and titre was compared between subjects of different geography,ethnicity and disease state.RESULTS:Ninety subjects were evaluated:21 Crohn’s disease(CD),32 ulcerative colitis(UC),29 healthy controls,and 8 IBD patient relatives.Forty eight subjects were Australian(29 Caucasian and 19 ethnic Han Chinese)and 42 were from HK(all Han Chinese).Caucasian CD patients had a significantly higher antibody prevalence of gASCA(67%vs 3%,P<0.001),ALCA(44%vs 6%,P=0.005),and AMCA(67%vs 15%,P=0.002),whereas HK CD patients had a higher prevalence of only AMCA(58%vs 25%,P=0.035),when compared with UC and healthy subjects in both countries.Caucasian CD had significantly higher gASCA prevalence(67%vs 0%,P<0.001)and titre(median59 vs 9,P=0.002)than HK CD patients.Prevalence and titres of ALCA,ACCA and AMCA did not differ between CD in the two countries.Presence of at least one antibody was higher in Caucasian than HK CD patients(100%vs 58%,P=0.045).pANCA did not differ between countries or ethnicity.CONCLUSION:Serologic CD responses differ between HK Asian and Australian Caucasian patients.Different genetic,environmental or disease pathogenic factors may account for these differences.展开更多
There is a consensus that both type 1 and type 2 diabetes are associated with a spectrum of cancers but the underlying mechanisms are largely unknown.On the other hand,there are ongoing debates about the risk associat...There is a consensus that both type 1 and type 2 diabetes are associated with a spectrum of cancers but the underlying mechanisms are largely unknown.On the other hand,there are ongoing debates about the risk association of insulin use with cancer.We have briefly reviewed recent related research on exploration of risk factors for cancer and pharmacoepidemiological investigations into drug use in diabetes on the risk of cancer,as well as the current understanding of metabolic pathways implicated in intermediary metabolism and cellular growth.Based on the novel findings from the Hong Kong Diabetes Registry and consistent experimental evidence,we argue that use of insulin to control hyperglycemia is unlikely to contribute to increased cancer risk and that dysregulations in the AMPactivated protein kinase pathway due to reduced insulin action and insulin resistance,the insulin-like growth factor-1(IGF-1)-cholesterol synthesis pathway and renin-angiotensin system,presumably due to reduced insulin secretion and hyperglycemia,may play causal roles in the increased risk of cancer in diabetes.Further exploration into the possible causal relationships between abnormalities of these pathways and the risk of cancer in diabetes is warranted.展开更多
Coronary artery calcification （CAC） is highly prevalent in patients with coronary heart disease （CHD） and is associated with major adverse cardiovascular events. There are two recognized type of CAC--intimal and m...Coronary artery calcification （CAC） is highly prevalent in patients with coronary heart disease （CHD） and is associated with major adverse cardiovascular events. There are two recognized type of CAC--intimal and medial calcification, and each of them have specific risk factors. Several theories about the mechanism of vascular calcification have been put forward, and we currently believe that vascular calcification is an active, regulated process. CAC can usually be found in patients with severe CHD, and this asymptomatic phenomenon make early diagnosis of CAC important. Coronary computed tomographic angiography is the main noninvasive tool to detect calcified lesions. Measurement of coronary artery calcification by scoring is a reasonable metric for cardiovascular risk assessment in asymptomatic adults at intermediate risk. To date, effective medical treatment of CAC has not been identified. Several strategies of percutaneous coronary interven- tion have been applied to CHD patients with CAC, but with unsatisfactory results. Prognosis of CAC is still a major problem of CHD pa- tients. Thus, more details about the mechanisms of CAC need to be elucidated in order to improve the understanding and treatment of CAC.展开更多
Epstein-Barr virus(EBV)-associated gastric carcinoma(EBVaGC)comprises nearly 10%of gastric carcinoma cases worldwide.Recently,it was recognised to have unique clinicopathologic characteristics,including male predomina...Epstein-Barr virus(EBV)-associated gastric carcinoma(EBVaGC)comprises nearly 10%of gastric carcinoma cases worldwide.Recently,it was recognised to have unique clinicopathologic characteristics,including male predominance,lower rates of lymph node involvement,and better prognosis.EBVaGC is further characterised by abnormal hypermethylation of tumour suppressor gene promoter regions,causing down-regulation of their expression.In the present review,we critically discuss the role of EBV in gastric carcinogenesis,summarising the role of viral proteins and microRNAs with respect to aberrant methylation in EBVaGC.Given the role of epigenetic dysregulation in tumourigenesis,epigenetic modifiers may represent a novel therapeutic strategy.展开更多
We present a rare case of invasive liver abscess syndrome due to Klebsiella pneumoniae (K. pneumoniae) with metastatic meningitis and septic shock. A previously healthy, 55-year-old female patient developed fever, liv...We present a rare case of invasive liver abscess syndrome due to Klebsiella pneumoniae (K. pneumoniae) with metastatic meningitis and septic shock. A previously healthy, 55-year-old female patient developed fever, liver abscess, septic shock, purulent meningitis and metastatic hydrocephalus. Upon admission, the clinical manifestations, laboratory and imaging examinations were compatible with a diagnosis of K. pneumoniae primary liver abscess. Her distal metastasis infection involved meningitis and hydrocephalus, which could flare abruptly and be life threatening. Even with early adequate drainage and antibiotic therapy, the patient’s condition deteriorated and she ultimately died. To the best of our knowledge, this is the first case of K. pneumoniae invasive liver abscess syndrome with septic meningitis reported in China's Mainland. Our findings reflect the need for a better understanding of the epidemiology, risk factors, complications, comorbid medical conditions and treatment of this disease.展开更多
Matrix metalloproteinases(MMPs) are a family ofproteases using zinc-dependent catalysis to break down extracellular matrix(ECM) components, allowing cell movement and tissue reorganization. Like many other proteases, ...Matrix metalloproteinases(MMPs) are a family ofproteases using zinc-dependent catalysis to break down extracellular matrix(ECM) components, allowing cell movement and tissue reorganization. Like many other proteases, MMPs are produced as zymogens, an inactive form, which are activated after their release from cells. Hepatic ischemia/reperfusion(I/R) is associated with MMP activation and release, with profound effects on tissue integrity: their inappropriate, prolonged or excessive expression has harmful consequences for the liver. Kupffer cells and hepatic stellate cells can secrete MMPs though sinusoidal endothelial cells are a further source of MMPs. After liver transplantation, biliary complications are mainly attributable to cholangiocytes, which, compared with hepatocytes, are particularly susceptible to injury and ultimately a major cause of increased graft dysfunction and patient morbidity. This paper focuses on liver I/R injury and cholestasis and reviews factors and mechanisms involved in MMP activation together with synthetic compounds used in their regulation. In this respect, recent data have demonstrated that the role of MMPs during I/R may go beyond the mere destruction of the ECM and may be much more complex than previously thought. We thus discuss the role of MMPs as an important factor in cholestasis associated with I/R injury.展开更多
More evidence has underscored the importance of Hippo signaling pathway in gastrointestinal tissue homeostasis, whereas its deregulation induces tumorigenesis. Yes-associated protein 1(YAP1) and its close paralog TAZ,...More evidence has underscored the importance of Hippo signaling pathway in gastrointestinal tissue homeostasis, whereas its deregulation induces tumorigenesis. Yes-associated protein 1(YAP1) and its close paralog TAZ, transcriptional co-activator with a PDZbinding motif, function as key effectors negatively controlled by the Hippo pathway. YAP1/TAZ exerts oncogenic activities by transcriptional regulation via physical interaction with TEAD transcription factors. In various cancers, Hippo pathway cross-talks with pro- or anti-tumorigenic pathways such as GPCR, Wnt/β-catenin, Notch and TGF-β signaling and is deregulated by multiple factors including cell density/junction and micro RNAs. As YAP1 expression is significantly associated with poor prognosis of gastric and other gastrointestinal cancers, detailed delineation of Hippo regulation in tumorigenesis provides novel insight for therapeutic intervention. In current review, we summarized the recent research progresses on the deregulation of Hippo pathway in the gastrointestinal tract including stomach and discuss the molecular consequences leading to tumorigenesis.展开更多
基金supported by Fujian Provincial Natural Science(2020J01122587)National Natural Science Foundation of China(82103355,82102255,and 82222901)+1 种基金RGC Theme-based Research Scheme(T12-703/19-R)Research grants Council-General Research Fund(14117422 and 14117123)。
文摘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.
基金supported by the National Key R&D Program of China(2021YFC2501500)National Natural Science Foundation of China(82171476)。
文摘Purpose:The aim of the current study was to investigate the association of accelerometer-measured sleep duration and different intensities of physical activity(PA)with the risk of incident type 2 diabetes in a population-based prospective cohort study.Methods:Altogether,88,000 participants(mean age=62.2±7.9 years,mean±SD)were included from the UK Biobank.Sleep duration(short:<6 h/day;normal:6-8 h/day;long:>8 h/day)and PA of different intensities were measured using a wrist-won accelerometer over a 7-day period between 2013 and 2015.PA was classified according to the median or World Health Organization-recommendation:total volume of PA(high,low),moderate-to-vigorous PA(MVPA)(recommended,not recommended),and light-intensity PA(high,low).Incidence of type 2diabetes was ascertained using hospital records or death registries.Results:During a median follow-up of 7.0 years,1615 incident type 2 diabetes cases were documented.Compared with normal sleep duration,short(hazard ratio(HR)=1.21,95%confidence interval(95%CI):1.03-1.41)but not long sleep duration(HR=1.01,95%CI:0.89-1.15)was associated with excessive type 2 diabetes risk.This increased risk among short sleepers seems to be protected against by PA.Compared with normal sleepers with high or recommended PA,short sleepers with low volume of PA(HR=1.81,95%CI:1.46-2.25),not recommended(below the World Health Organization-recommended level of)MVPA(HR=1.92,95%CI:1.55-2.36),or low light-intensity PA(HR=1.49,95%CI:1.13-1.90)had a higher risk of type 2 diabetes,while short sleepers with a high volume of PA(HR=1.14,95%CI:0.88-1.49),recommended MVPA(HR=1.02,95%CI:0.71-1.48),or high light-intensity PA(HR=1.14,95%CI:0.92-1.41)did not.Conclusion:Accelerometer-measured short but not long sleep duration was associated with a higher risk of incident type 2 diabetes.A higher level of PA,regardless of intensity,potentially ameliorates this excessive risk.
基金This study was partially supported by an unrestricted grant from Gilead Sciences(CAP-Asia Study-IN-US-989-5334).
文摘Background:Nonalcoholic fatty liver disease(NAFLD)is associated with impaired renal function,and both diseases often occur alongside other metabolic disorders.However,the prevalence and risk factors for impaired renal function in patients with NAFLD remain unclear.The objective of this study was to identify the prevalence and risk factors for renal impairment in NAFLD patients.Methods:All adults aged 18-70 years with ultrasound-diagnosed NAFLD and transient elastography examination from eight Asian centers were enrolled in this prospective study.Liver fibrosis and cirrhosis were assessed by FibroScan-aspartate aminotransferase(FAST),Agile 3+and Agile 4 scores.Impaired renal function and chronic kidney disease(CKD)were defined by an estimated glomerular filtration rate(eGFR)with value of<90 mL/min/1.73 m^(2) and<60 mL/min/1.73 m^(2),respectively,as estimated by the CKD-Epidemiology Collaboration(CKD-EPI)equation.Results:Among 529 included NAFLD patients,the prevalence rates of impaired renal function and CKD were 37.4%and 4.9%,respectively.In multivariate analysis,a moderate-high risk of advanced liver fibrosis and cirrhosis according to Agile 3+and Agile 4 scores were independent risk factors for CKD(P<0.05).Furthermore,increased fasting plasma glucose(FPG)and blood pressure were significantly associated with impaired renal function after controlling for the other components of metabolic syndrome(P<0.05).Compared with patients with normoglycemia,those with prediabetes[FPG≥5.6 mmol/L or hemoglobin A1c(HbA1c)≥5.7%]were more likely to have impaired renal function(P<0.05).Conclusions:Agile 3+and Agile 4 are reliable for identifying NAFLD patients with high risk of CKD.Early glycemic control in the prediabetic stage might have a potential renoprotective role in these patients.
文摘Hepatitis due to hepatitis B virus(HBV)reactivation can be serious and potentially fatal,but is preventable.HBV reactivation is most commonly reported in patients receiving chemotherapy,especially rituximab-containing therapy for hematological malignancies and those receiving stem cell transplantation.Patients with inactive and even resolved HBV infection still have persistence of HBV genomes in the liver.The expression of these silent genomes is controlled by the immune system.Suppression or ablation of immune cells,most importantly B cells,may lead to reactivation of seemingly resolved HBV infection.Thus,all patients with hematological malignancies receiving anticancer therapy should be screened for active or resolved HBV infection by blood tests for hepatitis B surface antigen(HBsAg)and antibody to hepatitis B core antigen.Patients found to be positive for HBsAg should be given prophylactic antiviral therapy.For patients with resolved HBV infection,there are two approaches.The first is pre-emptive therapy guided by serial HBV DNA monitoring,and treatment with antiviral therapy as soon as HBV DNA becomes detectable.The second approach is prophy-lactic antiviral therapy,particularly for patients receiving high-risk therapy,especially anti-CD20 monoclonal antibody or hematopoietic stem cell transplantation.Entecavir and tenofovir are the preferred antiviral choices.Many new effective therapies for hematological malignancies have been introduced in the past decade,for example,chimeric antigen receptor(CAR)-T cell therapy,novel monoclonal antibodies,bispecific antibody drug conjugates,and small molecule inhibitors,which may be associated with HBV reactivation.Although there is limited evidence to guide the optimal preventive measures,we recommend antivi-ral prophylaxis in HBsAg-positive patients receiving novel treatments,including Bruton’s tyrosine kinase inhibitors,B-cell lymphoma 2 inhibitors,and CAR-T cell therapy.Further studies are needed to determine the risk of HBV reactivation with these agents and the best prophylactic strategy.
文摘With advances in targeted and personalized treatment for lung cancer, molecular analysis of tumors is routinely performed for sequencing of treatment options in patients with advanced non-small-cell lung cancer (NSCLC). Oncogene addiction due to driver mutations includes EGFR exon 20 insertion mutations, MET amplification, EML4-AL, KRAS G12C point mutations, RET rearrangements, HER2 amplification and mutations, and FGFR amplification and translocations. A re-biopsy at the time of tumor recurrence or progression after first-line treatment failure is important for further molecular assessment and personalized therapy. However, repeat tumor biopsies are fraught with challenges including access to the tumor, sample inadequacy, patient consent, patient performance status, safety, or physician’s choice or assessment. Cytological specimens are gaining importance but are limited due to validation difficulties. Liquid biopsies, which are minimally invasive have shown promise to assess dynamic biomarkers using ctDNA analysis and are thus frequently considered in routine clinical practice in advanced NSCLC patients to guide further targeted treatment. Here we present a comprehensive review that emphasizes the significance of performing tumor re-biopsy in advanced stage NSCLC patients following resistance to first-line treatment and simultaneously highlights the current challenges in performing the same and the current status and future perspectives of liquid biopsy in NSCLC.
基金Department of science and Technology/Technology Development Program/Biomedical Device and Technology Development,Govt.Of India for the grant allocated for this project。
文摘The overall incidence and burden caused by breast cancer is increasing,affecting the global socio-economic development and life expectancy[1].According to“WHO Global Breast Cancer Initiative(GBCI)reports”,if the mortality rate due to breast cancer can be reduced by 2.4%annually,we may prevent 2.5 million breast cancer deaths between2020-2040.
基金supported by the National Natural Science Foundation of China(81772850 and 82273300)。
文摘Emerging evidence suggests that microbial dysbiosis plays vital roles in many human cancers.However,knowledge of whether the microbial community in thyroid tumor is related to tumorigenesis remains elusive.In this study,we aimed to explore the microbial community in thyroid tissues and its contribution to papillary thyroid cancer(PTC).In parallel,we performed microbial profiling and transcriptome sequencing in the tumor and adjacent normal tissues of a large cohort of 340 PTC and benign thyroid nodule(BTN)patients.Distinct microbial signatures were identified in PTC,BTN,and their adjacent nontumor tissues.Intra-thyroid tissue bacteria were verified by means of bacteria staining,fluorescence in situ hybridization,and immunoelectron microscopy.We found that 17 bacterial taxa were differentially abundant in PTC compared with BTN,which included enrichment in PTC of the pathobionts Rhodococcus,Neisseria,Streptococcus,Halomonas,and Devosia,and depletion of the beneficial bacteria Amycolatopsis.These differentially abundant bacteria could differentiate PTC tumor tissues(PTC-T)from BTN tissues(BTN-T)with an area under the curve(AUC)of 81.66%.Microbial network analysis showed increased correlation strengths among the bacterial taxa in PTC-T in comparison with BTN-T.Immunefunction-corresponding bacteria(i.e.,Erwinia,Bacillus,and Acinetobacter)were found to be enriched in PTC with Hashimoto’s thyroiditis.Moreover,our integrative analysis revealed that the PTC-enriched bacteria had a positive association with key PTC-oncogenic pathway-related genes,including BRAF,KRAS,IRAK4,CTNNB1,PIK3CA,MAP3K7,and EGFR.In conclusion,our results suggest that intratumor bacteria dysbiosis is associated with the thyroid tumorigenesis and oncogenic signaling pathways of PTC.
基金supported by the National Natural Science Foundation of China(82103355 and 82222901)Research Grants Council-General Research Fund(RGC-GRF+2 种基金14117422)Health and Medical Research Fund,Hong Kong(08191336)Vice-Chancellor’s Discretionary Fund CUHK.
文摘Non-alcoholic steatohepatitis(NASH)is a severe form of non-alcoholic fatty liver disease without effective treatment.The traditional Chinese medicine formulation Pien Tze Huang(PTH)can suppress inflammatory diseases.Here,we evaluate the effects of PTH on the evolution of NASH and its underlying mechanisms.We 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 peroxidation.Moreover,ten days of PTH treatment after the onset of NASH significantly ameliorated MCD diet-induced steatosis and liver injury in mice.Through the metagenomic sequencing of stool samples,we found that PTH administration restored the gut microbiota with enrichment of probiotics including Lactobacillus acidophilus(L.acidophilus),Lactobacillus plantarum,Lactococcus lactis,and Bacillus subtilis.The enriched L.acidophilus prevented MCD diet-induced steatohepatitis.In 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 expression.Our metabolomic analysis via liquid chromatography-mass spectrometry profiling identified the alteration in the metabolism of bile acids in the portal vein of PTHtreated mice.We further confirmed that an intact gut microbiota is necessary for PTH to exhibit antisteatohepatitis effects.In conclusion,PTH protects against steatohepatitis development by modulating the gut microbiota and metabolites.PTH is a potential promising prophylactic and therapeutic option for patients with NASH.
基金funded by a Croucher Innovation Award(CIA20CU01)from the Croucher Foundationthe General Research Fund(14100122)+4 种基金the Collaborative Research Fund(C6027-19GF&C7074-21GF)the Area of Excellence Scheme(AoE/M-604/16)of the Research Grants Councilthe University Grants Committee of Hong Kong,Chinathe Excellent Young Scientists Fund(Hong Kong and Macao,China)(82122001)from the National Natural Science Foundation of Chinathe Lo’s Family Charity Fund Limited(all to HK).
文摘Precise chemical cue presentation alongside advanced brainwide imaging techniques is important to the study of chemosensory processing in animals.Nevertheless,the dynamic nature of chemical-carrying media,such as water or air,poses a significant challenge for delivering highly-controlled chemical flow to an animal subject.Moreover,contact-based cue manipulation and delivery easily shift the position of the animal subject,which is often undesirable for high-quality brain imaging.Additionally,more advanced interfacing tools that align with the diverse range of body part sizes of an animal,ranging from micrometer-scale neurons to meter-long limbs,are much needed.This is particularly crucial when dealing with dimensions that are beyond the reach of conventional experimental tools.
文摘The complement system plays a crucial role in the innate defense against common pathogens. Activation of complement leads to robust and efficient proteolytic cascades, which terminate in opsonization and lysis of the pathogen as well as in the generation of the classical inflammatory response through the production of potent proinflammatory molecules. More recently, however, the role of complement in the immune response has been expanded due to observations that link complement activation to adaptive immune responses. It is now appreciated that complement is a functional bridge between innate and adaptive immune responses that allows an integrated host defense to pathogenic challenges. As such, a study of its functions allows insight into the molecular underpinnings of host-pathogen interactions as well as the organization and orchestration of the host immune response. This review attempts to summarize the roles that complement plays in both innate and adaptive immune responses and the consequences of these interactions on host defense.
文摘Gastric cancer remains a global killer with a shifting burden from the developed to the developing world. The cancer develops along a multistage process that is defined by distinct histological and pathophysiological phases. Several genetic and epigenetic alterations mediate the transition from one stage to another and these include mutations in oncogenes, tumour suppressor genes and cell cycle and mismatch repair genes. The most significant advance in the fight against gastric caner came with the recognition of the role of Helicobacter pylori （H pylori） as the most important acquired aetiological agent for this cancer. Recent work has focussed on elucidating the complex host/microbial interactions that underlie the neoplastic process. There is now considerable insight into the pathogenesis of this cancer and the prospect of preventing and eradicating the disease has become a reality. Perhaps more importantly, the study of H pylori-induced gastric carcinogenesis offers a paradigm for understanding more complex human cancers. In this review, we examine the molecular and cellular events that underlie Hpyloriinduced gastric cancer.
基金Supported by Collaborative Research Fund(CUHK3/CRF/12RHKU3/CRF11R)of the Research Grant Council Hong Kong+2 种基金National Basic Research Program of China,973 Program,No.2013CB531401CUHK Focused Investments Scheme B to HY LanTheme-based Research Scheme of the Hong Kong Re-search Grants Council,No.T12-403-11
文摘Chronic hepatitis B(CHB)virus infection is a global public health problem,affecting more than 400 million people worldwide.The clinical spectrum is wide,ranging from a subclinical inactive carrier state,to progressive chronic hepatitis,cirrhosis,decompensation,and hepatocellular carcinoma.However,complications of hepatitis B virus(HBV)-related chronic liver disease may be reduced by viral suppression.Current international guidelines recommend first-line treatment of CHB infection with pegylated interferon,entecavir,or tenofovir,but the optimal treatment for an individualpatient is controversial.The indications for treatment are contentious,and increasing evidence suggests that HBV genotyping,as well as serial on-treatment measurements of hepatitis B surface antigen and HBV DNA kinetics should be used to predict antiviral treatment response.The likelihood of achieving a sustained virological response is also increased by extending treatment duration,and using combination therapy.Hence the paradigm for treatment of CHB is constantly evolving.This article summarizes the different indications for treatment,and systematically reviews the evidence for the efficacy of various antiviral agents.It further discusses the shortcomings of current guidelines,use of rescue therapy in drug-resistant strains of HBV,and highlights the promising clinical trials for emerging therapies in the pipeline.This concise overview presents an updated practical approach to guide the clinical management of CHB.
文摘Hepatitis due to hepatitis B virus(HBV) reactivation can be severe and potentially fatal, but is preventable. HBV reactivation is most commonly reported in patients receiving cancer chemotherapy, especially rituximabcontaining therapy for hematological malignancies and those receiving stem cell transplantation. All patients with hematological malignancies receiving anticancer therapy should be screened for active or resolved HBV infection by blood tests for hepatitis B surface antigen(HBs Ag) and antibody to hepatitis B core antigen(antiHBc). Patients found to be positive for HBs Ag should be given prophylactic antiviral therapy to prevent HBV reactivation. For patients with resolved HBV infection, no standard strategy has yet been established to prevent HBV reactivation. There are usually two options. One is pre-emptive therapy guided by serial HBV DNA monitoring, whereby antiviral therapy is given as soon as HBV DNA becomes detectable. However, there is little evidence regarding the optimal interval and period of monitoring. An alternative approach is prophylactic antiviral therapy, especially for patients receiving highrisk therapy such as rituximab, newer generation of anti-CD20 monoclonal antibody, obinutuzumab or hematopoietic stem cell transplantation. This strategy may effectively prevent HBV reactivation and avoid the inconvenience of repeated HBV DNA monitoring. Entecavir or tenofovir are preferred over lamivudine as prophylactic therapy. Although there is no well-defined guideline on the optimal duration of prophylactic therapy, there is growing evidence to recommend continuing prophylactic antiviral therapy for at least 12 mo after cessation of chemotherapy, and even longer for those who receive rituximab or who had high serum HBV DNA levels before the start of immunosuppressive therapy. Many novel agents have recently become available for the treatment of hematological malignancies, and these agents may be associated with HBV reactivation. Although there is currently limited evidence to guide the optimal preventive measures, we recommend antiviral prophylaxis in HBs Ag-positive patients receiving novel treatments, especially the Bruton tyrosine kinase inhibitors and the phosphatidylinositol 3-kinase inhibitors, which are B-cell receptor signaling modulators and reduce proliferation of malignant B-cells. Further studies are needed to clarify the risk of HBV reactivation with these agents and the best prophylactic strategy in the era of targeted therapy for hematological malignancies.
文摘AIM:To study serological antibodies in Caucasians and Asians,in health and inflammatory bowel disease(IBD),in Australia and Hong Kong(HK).METHODS:Anti-glycan antibodies[anti-chitobioside(ACCA),anti-laminaribioside(ALCA)],and anti-mannobioside(AMCA),anti-Saccharomyces cervisiae(gASCA);and atypical perinuclear anti-neutrophil cytoplasmic antibody(pANCA)were tested in IBD patients,their unaffected relatives,and healthy controls in Australia and HK(China).Antibody status(positive or negative)and titre was compared between subjects of different geography,ethnicity and disease state.RESULTS:Ninety subjects were evaluated:21 Crohn’s disease(CD),32 ulcerative colitis(UC),29 healthy controls,and 8 IBD patient relatives.Forty eight subjects were Australian(29 Caucasian and 19 ethnic Han Chinese)and 42 were from HK(all Han Chinese).Caucasian CD patients had a significantly higher antibody prevalence of gASCA(67%vs 3%,P<0.001),ALCA(44%vs 6%,P=0.005),and AMCA(67%vs 15%,P=0.002),whereas HK CD patients had a higher prevalence of only AMCA(58%vs 25%,P=0.035),when compared with UC and healthy subjects in both countries.Caucasian CD had significantly higher gASCA prevalence(67%vs 0%,P<0.001)and titre(median59 vs 9,P=0.002)than HK CD patients.Prevalence and titres of ALCA,ACCA and AMCA did not differ between CD in the two countries.Presence of at least one antibody was higher in Caucasian than HK CD patients(100%vs 58%,P=0.045).pANCA did not differ between countries or ethnicity.CONCLUSION:Serologic CD responses differ between HK Asian and Australian Caucasian patients.Different genetic,environmental or disease pathogenic factors may account for these differences.
基金Supported by The Hong Kong Foundation for Research and Development in Diabetes,Lioa Wun Yuk Diabetes Memorial Fund,established under the auspices of the Chinese University of Hong Kong
文摘There is a consensus that both type 1 and type 2 diabetes are associated with a spectrum of cancers but the underlying mechanisms are largely unknown.On the other hand,there are ongoing debates about the risk association of insulin use with cancer.We have briefly reviewed recent related research on exploration of risk factors for cancer and pharmacoepidemiological investigations into drug use in diabetes on the risk of cancer,as well as the current understanding of metabolic pathways implicated in intermediary metabolism and cellular growth.Based on the novel findings from the Hong Kong Diabetes Registry and consistent experimental evidence,we argue that use of insulin to control hyperglycemia is unlikely to contribute to increased cancer risk and that dysregulations in the AMPactivated protein kinase pathway due to reduced insulin action and insulin resistance,the insulin-like growth factor-1(IGF-1)-cholesterol synthesis pathway and renin-angiotensin system,presumably due to reduced insulin secretion and hyperglycemia,may play causal roles in the increased risk of cancer in diabetes.Further exploration into the possible causal relationships between abnormalities of these pathways and the risk of cancer in diabetes is warranted.
基金This work were supported by the Beijing Municipal Administration of Hospitals Clinical Medicine Development of Special Funding Support （No. ZYLX201303）, the National Natural Science Foundation of China （No. 81470429, No.81270285）, and The capital health research and development of special （No 2011-2006-14）.
文摘Coronary artery calcification （CAC） is highly prevalent in patients with coronary heart disease （CHD） and is associated with major adverse cardiovascular events. There are two recognized type of CAC--intimal and medial calcification, and each of them have specific risk factors. Several theories about the mechanism of vascular calcification have been put forward, and we currently believe that vascular calcification is an active, regulated process. CAC can usually be found in patients with severe CHD, and this asymptomatic phenomenon make early diagnosis of CAC important. Coronary computed tomographic angiography is the main noninvasive tool to detect calcified lesions. Measurement of coronary artery calcification by scoring is a reasonable metric for cardiovascular risk assessment in asymptomatic adults at intermediate risk. To date, effective medical treatment of CAC has not been identified. Several strategies of percutaneous coronary interven- tion have been applied to CHD patients with CAC, but with unsatisfactory results. Prognosis of CAC is still a major problem of CHD pa- tients. Thus, more details about the mechanisms of CAC need to be elucidated in order to improve the understanding and treatment of CAC.
基金Supported by Research Grants of National Basic Research Program of China (973 Program, 2010CB529305)Innovation and Technology Support Programme, Hong Kong (ITS/214/12)
文摘Epstein-Barr virus(EBV)-associated gastric carcinoma(EBVaGC)comprises nearly 10%of gastric carcinoma cases worldwide.Recently,it was recognised to have unique clinicopathologic characteristics,including male predominance,lower rates of lymph node involvement,and better prognosis.EBVaGC is further characterised by abnormal hypermethylation of tumour suppressor gene promoter regions,causing down-regulation of their expression.In the present review,we critically discuss the role of EBV in gastric carcinogenesis,summarising the role of viral proteins and microRNAs with respect to aberrant methylation in EBVaGC.Given the role of epigenetic dysregulation in tumourigenesis,epigenetic modifiers may represent a novel therapeutic strategy.
基金Supported by the National Natural Science Foundation of China,No.81372623the Zhejiang Province Key Science and Technology Innovation Team,No.2013TD13
文摘We present a rare case of invasive liver abscess syndrome due to Klebsiella pneumoniae (K. pneumoniae) with metastatic meningitis and septic shock. A previously healthy, 55-year-old female patient developed fever, liver abscess, septic shock, purulent meningitis and metastatic hydrocephalus. Upon admission, the clinical manifestations, laboratory and imaging examinations were compatible with a diagnosis of K. pneumoniae primary liver abscess. Her distal metastasis infection involved meningitis and hydrocephalus, which could flare abruptly and be life threatening. Even with early adequate drainage and antibiotic therapy, the patient’s condition deteriorated and she ultimately died. To the best of our knowledge, this is the first case of K. pneumoniae invasive liver abscess syndrome with septic meningitis reported in China's Mainland. Our findings reflect the need for a better understanding of the epidemiology, risk factors, complications, comorbid medical conditions and treatment of this disease.
文摘Matrix metalloproteinases(MMPs) are a family ofproteases using zinc-dependent catalysis to break down extracellular matrix(ECM) components, allowing cell movement and tissue reorganization. Like many other proteases, MMPs are produced as zymogens, an inactive form, which are activated after their release from cells. Hepatic ischemia/reperfusion(I/R) is associated with MMP activation and release, with profound effects on tissue integrity: their inappropriate, prolonged or excessive expression has harmful consequences for the liver. Kupffer cells and hepatic stellate cells can secrete MMPs though sinusoidal endothelial cells are a further source of MMPs. After liver transplantation, biliary complications are mainly attributable to cholangiocytes, which, compared with hepatocytes, are particularly susceptible to injury and ultimately a major cause of increased graft dysfunction and patient morbidity. This paper focuses on liver I/R injury and cholestasis and reviews factors and mechanisms involved in MMP activation together with synthetic compounds used in their regulation. In this respect, recent data have demonstrated that the role of MMPs during I/R may go beyond the mere destruction of the ECM and may be much more complex than previously thought. We thus discuss the role of MMPs as an important factor in cholestasis associated with I/R injury.
基金General Research Fund(No.2140855RGC Reference No.CUHK14114414)from The Research Grants Council of Hong Kong+1 种基金National Natural Science Grant No.81201591 from ChinaDirect Grant for Research No.2014.2.002 from The Chinese University of Hong Kong
文摘More evidence has underscored the importance of Hippo signaling pathway in gastrointestinal tissue homeostasis, whereas its deregulation induces tumorigenesis. Yes-associated protein 1(YAP1) and its close paralog TAZ, transcriptional co-activator with a PDZbinding motif, function as key effectors negatively controlled by the Hippo pathway. YAP1/TAZ exerts oncogenic activities by transcriptional regulation via physical interaction with TEAD transcription factors. In various cancers, Hippo pathway cross-talks with pro- or anti-tumorigenic pathways such as GPCR, Wnt/β-catenin, Notch and TGF-β signaling and is deregulated by multiple factors including cell density/junction and micro RNAs. As YAP1 expression is significantly associated with poor prognosis of gastric and other gastrointestinal cancers, detailed delineation of Hippo regulation in tumorigenesis provides novel insight for therapeutic intervention. In current review, we summarized the recent research progresses on the deregulation of Hippo pathway in the gastrointestinal tract including stomach and discuss the molecular consequences leading to tumorigenesis.
