Gut Liver
Gut-Liver Axis and Sensing Microbes
Normal
Alcohol acetaldehyde
Intestinal dysbiosis
M ce ll
Inflammatory responses in the body to gut-derived and blood-borne pathogens occur in the liver and spleen, the major organs that remove bacteria and their lipopolysaccharide (LPS) from the bloodstream. Several mechanisms have been identified and proposed in this process that relies on a balance between the barrier functions of the gut and the ‘detoxifying’ capacity of the liver [1, 2]. The role of gut-derived LPS has been identified in various liver diseases [6, 7]. The liver has different mechanisms to ‘detoxify’ gut-derived LPS including host lipases [8] and the lack of this protective mechanism was shown to increase inflammatory responses [9]. There is a positive correlation between liver dysfunction and bacterial translocation [10, 11]. Increased gut permeability and/or LPS levels were also noted in liver disease associated with HIV and HCV infection, cirrhosis and cholestasis of pregnancy [6, 12, 13].
骨骼绑定的命名
骨骼绑定的命名骨骼绑定的命名骨骼绑定的制作心得骨骼绑定的命名：首先确定好骨骼是否使用IK_FK转换，如果有转换的话需要命名成为IK,SK,FK三种骨骼形式。
那么命名遵循以下的命名方式：角色名称_角色骨骼类别_角色骨骼名称_角色骨骼编号角色骨骼绑定名称：模型整体名称：Modeling骨骼名称：Joint控制器名称：Control角色名称_角色骨骼类别_角色骨骼名称_角色骨骼编号_控制器_组编号骨骼或者控制器的组用：角色名称_骨骼名称_骨骼编号_Group编号骨骼IK控制的设置：角色名称_IK_IK部位_控制器_组编号Breastbone 胸骨Tail 尾巴腰部SK：根关节####_Sk_Root脊柱####_SK_Back _A1脊柱####_SK_Back _A2脊柱####_SK_Back _A3脊柱####_SK_Back _A4颈椎####_SK_Chest腰部FK：根关节####_Fk_Root脊柱####_FK_Back _A1脊柱####_FK_Back _A2脊柱####_FK_Back _A3脊柱####_FK_Back _A4颈椎####_FK_Chest腰部IK：根关节####_Ik_Root脊柱####_IK_Back _A1脊柱####_IK_Back _A2脊柱####_IK_Back _A3脊柱####_IK_Back _A4颈椎####_IK_Chest腿部骨骼装配的命名：腿部是左右对称的所以需要以Left和Right来区分Left左Right 右腿部极向量约束Polevector腿部分为:大腿Hip小腿Knee脚踝Ankle脚掌Ball脚趾ToeTipHeel 脚后跟Foot脚Leg总的腿手臂和手指命名：手臂是左右对称的所以需要以Left和Right来区分Left左Right 右palm 手掌Specular锁骨Shoulder大臂ShoulderAdded与大臂从和的骨骼Elbow小臂Wrist手腕WristAdded与手腕从和的骨骼。
gut的用法
1. 取出…的内脏(或肠子)2. 把(城市、房屋等)抢劫一空，(从内部)劫掠(或破坏)：例句: Invaders gutted the city.
侵略者把城中的财物洗劫一空。3. (如用火等)毁坏…的内部；破坏…的主要力量；抽去(书籍等的)主要内容：例句: Fire gutted the building and left only the brick wall standing.
- 基于3个网页
hind gut..后食道
hind gut..后食道
hind gut
后食道
推荐文章 ...
hind 后
hind gut; hind intestine 后肠；后食道
hind leg 后腿 ...
- 基于2个网页
- 基于1个网页
3. 肠疝气
词博科技英语主科技词汇[220501-220600] ...
guttering 开沟法
gut-tie 肠绞窄; 肠疝气
Guttiferae 藤黄科 ...
- 基于6个网页
gut tie..肠扭转
bung hole (酒桶的)封塞孔 ...
- 基于4个网页
gut wire..钢丝切丸
gut wire..钢丝切丸
gut wire
钢丝切丸
集装箱相关 ...
grit 棱角砂
gut wire 钢丝切丸
degreasing 去油脂 ...
Gut's
网球魔童
《网球魔童》（Gut's）[第13集]（推荐！！
- 基于4个网页
gut-tie..肠绞窄 | 肠绞窄 肠疝气 | 肠疝气
EASL Clinical Practice Guidelines on Alcoholic Liver Disease
EASL Clinical Practical Guidelines:Management of AlcoholicLiver DiseaseEuropean Association for the Study of the Liver⇑,IntroductionAlcoholic liver disease(ALD)is the most prevalent cause of advanced liver disease in Europe.However,there has been lim-ited research investment into ALD despite its significant burden on the health of Europeans.This disparity is reflected by the ETOh score–the ratio of the estimated population mortality rate to the number of trials focused on a particular disease.The ETOh score for ALD is358,compared with1.4for hepatitis B,4.9for hepatitis C,and15.2for primary biliary cirrhosis[1].In recent years however,the mechanisms driving disease pro-gression and the natural history of ALD have been better defined and novel targets for therapy have been identified[2].In addition, significant clinical research has produced a clear framework for the evaluation of new therapies in particular in patients with alcoholic steatohepatitis(ASH).ALD is a complex disease,the successful management of which hinges on the integration of all the competences in public health,epidemiology,addiction behavior and alcohol-induced organ injury.Both primary intervention to reduce alcohol abuse and secondary intervention to prevent alcohol-associated mor-bidity and mortality rely on the coordinated action of multidisci-plinary teams established at local,national,and international levels.These guidelines are largely based on the issues raised during the EASL monothematic conference on ALD held in Athens in 2010.The guidelines have three main aims:(1)to provide physi-cians with clinical recommendations;(2)to emphasize the fact that alcohol can cause several liver diseases(steatosis,steatohep-atitis,cirrhosis),all of which may coexist in the same patient;(3) to identify areas of interest for future research,including clinical trials.The evidence and recommendations in these guidelines have been graded according to the Grading of Recommendations Assessment Development and Evaluation(GRADE)system[3]. The strength of recommendations thus reflects the quality of underlying evidence.The principles of the GRADE system have been enunciated.The quality of the evidence in these clinical practical guidelines(CPGs)has been classified into one of three levels:high(A),moderate(B)or low(C).The GRADE system offers two grades of recommendation:strong(1)or weak(2) (Table1).The CPGs thus consider the quality of evidence:the higher the quality of evidence,the more likely a strong recom-mendation is warranted;the greater the variability in values and preferences,or the greater the uncertainty,the more likely a weaker recommendation is warranted.Burden of ALDBurden of alcohol-related disease and injuryAlcohol consumption is responsible for3.8%of global mortality and4.6%of disability-adjusted life-years(DALYs)lost due to pre-mature death[4].The attributable burden in Europe,with6.5%of all deaths and11.6%of DALYs attributable to alcohol,is the high-est proportion of total ill health and premature deaths due to alcohol of all WHO regions[4,5].Europe shows particularly large sex differences in burden:the deaths attributable to alcohol being11.0%and 1.8%for men and women,respectively.The young account for a disproportionate amount of this disease bur-den,with an alcohol-associated mortality over10%and25%of female and male youth,respectively[6].Burden of ALD in EuropeThe burden of compensated alcohol cirrhosis among the general population and heavy drinkers is not well known.The develop-ment of non-invasive methods to detect significant liverfibrosis (e.g.,elastography,serum markers)should help in elucidating this issue.A recent study in France indicates that alcohol abuse accounts for up to one third of liverfibrosis cases[7].The best comparative proxy for the burden of ALD is mortality from liver cirrhosis as a whole,although as discussed later this has its lim-itations.Mortality rates from liver cirrhosis vary considerably between European countries[8]with a15-fold variation between the highest and lowest national rates[9].However,Europe is essentially divided into two,with Eastern European states tend-ing to have higher rates than the others[8].Time trends in liver cirrhosis mortality over the past30years show very heterogeneous patterns between countries.AbouthalfJournal of Hepatology2012vol.xxx jxxx–xxxKeywords:Alcoholic liver disease;EASL guidelines;Pathogenesis;Diagnosis;Treatment.Received4April2012;accepted4April2012⇑Correspondence:EASL Office,7rue des Battoirs,CH1205Geneva,Switzerland.Tel.:+41228070360;fax:+41223280724.E-mail address:easloffice@easloffice.eu.Contributors:Chairmen:Philippe Mathurin;Antoine Hadengue;RamonBataller.Clinical Practice Guidelines Members:Giovanni Addolorato;PatriziaBurra;Alastair Burt;Juan Caballeria;Helena Cortez-Pinto;Chris P.Day;Ewan H.Forrest;Antoni Gual;David A.Leon;Anna Lligoña;Peter Jepsen;Sebastian Mueller;Georges-Philippe Pageaux;Tania Roskams;Helmut K.Seitz;Felix Stickel.EASLGoverning Board Representative:Mark Thursz.Reviewers:Sylvie Naveau;TimMorgan;Frederik Nevens.the countries of Europe,including Austria,France,Germany,Italy,Portugal,and Spain as well as two Eastern European countries (Hungary and Romania)have experienced sharp declines in liver cirrhosis mortality [9],whereas the Western countries of Finland,Ireland,and the United Kingdom [10],as well as a larger number of Eastern European countries including Estonia [11],Lithuania,Poland,and Russia have increasing rates.In terms of alcohol-related hospital admissions,for example,parallel to the upward trend in liver cirrhosis mortality,general hospital admissions [12],and admissions to intensive care units with ALD have risen sharply in the United Kingdom [13].Limitations to estimate the burden of ALDThe extent of international variation and trends in ALD is difficult to determine.Mortality data from liver disease is available for most countries,and to this extent liver cirrhosis mortality is fre-quently used as the indicator of choice.However,it is not possi-ble to reliably separate out alcoholic from non-alcoholic cirrhosis mortality.In an undetermined proportion of deaths in which alcohol is the key factor,the certifying doctor may choose not to explicitly mention alcohol on the death certificate [14].The extent of this bias is unknown,but it is likely to vary by country,sex,age,and era.For this reason,emphasis is usually given to analyzing mortality from liver cirrhosis regardless of whether it is specified as alcoholic or not [15].These factors,taken together,mean that at the present time our best estimates about the inter-national variation in the burden of ALD,based on mortality from liver cirrhosis as a whole,need to be interpreted with caution.There is a clear need to perform large-scale epidemiological stud-ies to determine the prevalence of compensated ALD in the gen-eral population and the weight of ALD as a cause of cirrhosis.Types of alcohol and patterns of consumptionEuropean countries vary considerably in terms of per capita alco-hol consumption,predominant beverage type,and the extent to which drinkers imbibe substantial quantities on single occasions (binge drinking)[6].In order to propose a consensual definition,the National Institute of Alcohol Abuse and Alcoholism defines binge drinking episodes as consumption of five or more drinks (male)or four or more drinks (female)in the space of about 2h [16].These differences in type and pattern of consumption tendto fall along an East–West divide [17].While per capita alcohol consumption is strongly correlated with liver cirrhosis mortality rates across countries [18],there remains uncertainty about whether these other dimensions of drinking behavior in a popu-lation are related to risk [19,20].There are several aspects to this.Firstly,does beverage type matter above and beyond volume of ethanol consumed [21]?Secondly,does drinking to intoxication (sometimes referred to as binge drinking)confer a particular risk?Thirdly,what is the contribution to the burden of ALD induced by the consumption of substances that may contain hep-atotoxic substances in addition to ethanol [20,22,23]?This latter class of drink includes fruit brandies,which are frequently con-sumed in Hungary,for example [24]as well as home brewed alcohols that are drunk in Russia [25]and other parts of the for-mer Soviet Union [26].Risk threshold of alcohol consumption for liver cirrhosisAn important aspect of public health policy concerning alcohol has been the attempt to establish a safe threshold for consump-tion.This revolves primarily around the extent to which moder-ate alcohol consumption is cardioprotective [27,28].This positive effect of alcohol,if real,can then offset the large array of negative health consequences of even moderate alcohol consumption.For many individual diseases such as liver cirrhosis;however,there is no a priori reason to believe a threshold effect exists,as risk appears to increase steeply with the amount of alcohol con-sumed.In a meta-analysis of daily consumption levels in relation to cirrhosis,patients taking 25g of ethanol a day were at higher risk of cirrhosis than non-drinkers [29].A more recent meta-analysis found increased risks of mortality from liver cirrhosis among men and women drinking 12–24g of ethanol per day [30].Indeed,among women,a significant increase was also seen for those drinking up to 12g/day.These levels of consumption (<25g/day)are appreciably lower than most public health rec-ommendations for overall safe levels of consumption.The human evidence to date therefore suggests that if a threshold exists,it is very low,and may in fact be difficult to detect because of limitations in measuring consumption below 10–12g per day.It should be noted that neither meta-analysis was able to dis-tinguish between the effects of daily consumption from the effects of ‘‘binge’’drinking.To this extent little is known aboutTable 1.Grading of evidence and recommendations (adapted from the GRADEsystem).Clinical practical guidelines2Journal of Hepatology 2012vol.xxx jxxx–xxxthresholds as applied to ‘‘binge’’drinking.Further clinical and experimental studies are required to define the role of ‘‘binge’’in the pathogenesis of ALD and the underlying mechanisms.Finally,risk of cirrhosis is almost certainly related to the length of time over which an individual has drunk regularly and not simply to the usual amount consumed.Conversely,there is some clinical evidence that cessation of drinking at any point in the natural history of the disease reduces the risks of disease progression and occurrence of complications from cirrhosis.Public health implicationsEven though there remain uncertainties about the precise burden of and trends in ALD in Europe,there is no doubt that in many countries it is very substantial and or increasing.While improve-ments in treatment are essential,developing population-based policies to reduce levels of harmful and hazardous consumption are a priority.More broadly,there is increasing recognition of the heavy social,health,and economic burdens imposed by heavy alcohol drinking and the policies to reduce harm caused by alco-hol,need to be urgently implemented [31].Several meta-analyses have evaluated the efficacy and cost efficacy of different policy targeted areas [32].The most cost-effective policies are those that reduce availability of alcohol,either through the pricing policies or the hours and places of sale,as well as implementation of min-imum age purchase laws.Statements(1)Alcohol abuse is a major cause of preventable liver diseaseworldwide.(2)Per capita alcohol consumption is strongly correlated withliver cirrhosis mortality rates across countries.Any evi-dence based policy in Europe need to implement preven-tive measures aimed at reducing alcohol consumption at the population level.(3)The binge drinking pattern is becoming increasingly preva-lent,mainly among young individuals,but its impact on liver disease is unknown.RecommendationsSuggestions for future studies(1)Large epidemiological studies using non-invasive methodsshould establish the prevalence of all forms of alcoholic liver disease in the general population.(2)Studies evaluating the short and long-term impact of bingedrinking in the development and severity of ALD are par-ticularly needed.Management of alcohol abuse and alcohol dependenceA large number of European citizens drink alcohol.Europe has the highest per capita alcohol consumption (11L of pure alcohol per year in population P 15years old).Fifteen percent of Europe-ans (58million citizens)drink excessively (>40g per day in men,and >20g per day in women),with a higher proportion among males and young people.Alcohol abuse and alcohol dependence must be seen as differ-ent forms of the same disorder,as it is recognized in the new DSM-V draft.Alcohol abuse is not recognized as a disorder in the ICD-10,and in fact the WHO uses the terms hazardous and harmful alcohol use instead of alcohol abuse.The term ‘risky drinker’is commonly used to define people who drink excessively.Drinking habits of patients need to be routinely screened in patients with liver diseases,and this must be done with tools that have proven its reliability [16].There is a common trend to measure alcohol intake in grams per day or grams per week.Calculations are usually made counting standard drink units [33].The content of a standard drink may differ from country to country,but in Europe most of the countries have fixed their standard drink unit to an ethanol content of 8–10g.Even though measurements in standard drinks may lose accuracy,they are reliable,save time,and are particularly useful in busy clinical settings.Screening tools to detect alcohol abuse and dependenceQuantity-frequency questionnaires and retrospective diaries (time-line follow back)can be used to calculate patients’drinking habits.The former are usually preferred for their simplicity,but they must include data on both working and weekend days.A good alternative to quantity frequency questionnaires is the use of screening instruments to screen risky drinking and alcohol dependence.There are many tools that have been validated and translated into many languages,but the AUDIT (Alcohol Use Dis-orders Inventory Test)remains the ‘gold standard’.Developed by the WHO in 1982,it has proven to have good sensitivity and specificity in clinical settings across different countries [34].The AUDIT has 10questions that explore consumption (1–3),dependence (4–6),and alcohol related problems (7–10)(Table 2).There are two cut-off points,one for dependence and one for risky drinking.Shorter versions have been developed.The AUDIT C includes just the first three questions of the AUDIT and is reliable for the screening of ‘risky drinking’[35,36].The NIAAA (National Institute of Alcohol Abuse and Alcoholism)rec-ommends using the third question of the AUDIT (How often do you have six or more drinks in one occasion?)as a single screen-ing question,which should be followed by the whole AUDIT in case the answer is rated positive [16].JOURNAL OF HEPATOLOGYJournal of Hepatology 2012vol.xxx j xxx–xxx3Screening of patients with psychiatric disordersAlcoholics have a high psychiatric co-morbidity.In general,pop-ulation surveys of alcoholics show high prevalence of anxiety dis-orders,affective disorders,and schizophrenia [37].Anxiety and affective disorders may be independent or concurrent with alco-hol dependence.Independent disorders will need specific treat-ment,while concurrent disorders may disappear once the patient is weaned off alcohol.Alcoholics have a higher risk of developing other addictions,including nicotine.Alcoholics tend to be heavier smokers and the treatment of nicotine dependence requires more intensive support [38].Alcoholics who are polydrug users are difficult to manage and should be systematically referred to specialized treatment.Data suggest that alcohol dependence appears within 5years before the patient is referred to specialist treatment.Special attention should be paid to the coordination between hepatolo-gists and addiction specialists (psychiatrists,psychologists,and social workers)in order to reduce the gap between the signs of alcohol dependence appearing and referral.Because cigarette smoking and alcohol abuse are synergistic in causing cardiovas-cular diseases and cancer,including HCC,hepatologists are encouraged to promote and assist smoking cessation among patients with ALD [39].Management of alcohol withdrawal syndromeAlcohol withdrawal syndrome (AWS)is a severe medical condi-tion affecting alcohol-dependent patients who suddenly discon-tinue or decrease alcohol consumption.Light or moderate AWS usually develops within 6–24h after the last drink and symptoms may include increase in blood pressure and pulse rate,tremors,hyperreflexia,irritability,anxiety,headache,nausea,and vomit-ing.These symptoms may progress to more severe forms of AWS,characterized by delirium tremens,seizures,coma,cardiac arrest,and death [40].Severity scores for AWS are potentially useful in the management of patients.However,these scores are insufficiently validated at this time,especially in the setting of ALD.Benzodiazepines are considered the ‘gold standard’treat-ment for AWS,given their efficacy to reduce both withdrawal symptoms and the risk of seizures and/or delirium tremens [41,42].Long-acting benzodiazepines (e.g.diazepam,chlordiaz-epoxide)provide more protection against seizures and delirium,but short and intermediate-acting benzodiazepines (e.g.loraze-pam,oxazepam)are safer in elderly patients and those with hepatic dysfunction [43].In Europe,clomethiazole is also used to treat AWS [44].Given the side-effects of benzodiazepines in patients with advanced liver disease and potential for abuse,preliminary research has been conducted to identify new medications for AWS,such as clonidine,atenolol,carbamazepine,valproic acid,gamma-hydroxybutyrate,topiramate,baclofen,gabapentin,and pregabalin [45].Whilst sufficient evidence in favor of their use is lacking,topiramate and baclofen have promise given their potential to be used for AWS first [46,47],and then to prevent relapse.Medical therapy of alcohol dependence in patients with ALDAlcohol abstinence represents a critical goal in patients with ALD since abstinence improves the clinical outcomes of all stages of ALD.In the past,disulfiram was the only drug available forTable 2.AUDIT questionnaire [36].To score the AUDIT questionnaire,sum the scores for each of the 10questions.A total P 8for men up to age 60,or P 4for women,adolescents,or men over age 60is considered a positive screeningtest.Clinical practical guidelines4Journal of Hepatology 2012vol.xxx jxxx–xxxalcoholism.Disulfiram represents an effective alcohol pharmaco-therapy [48];however,disulfiram should be avoided in patients with severe ALD because of possible hepatotoxicity [49].More recently,the growing understanding of the neurobiology of alco-holism has led to the development of effective pharmacologic agents that can complement psychosocial treatments,in particu-lar naltrexone [50]and acamprosate [51].Both naltrexone and acamprosate are approved to treat alcoholism;however,these drugs have not been tested in patients with cirrhosis.The opioid antagonist naltrexone has been intensively evaluated,especially the oral formulation [52].A large trial also showed the efficacy of an intramuscular formulation of naltrexone in alcoholism [53].Given the potential for hepatotoxicity,naltrexone has not been tested in patients with ALD,and its use in this population is not recommended.Acamprosate is a modulator of the glutama-tergic receptor system and a meta-analysis of 24randomized controlled trials confirmed its efficacy as an alcohol pharmaco-therapy [54].Based on some clinical trials,gamma-hydroxybu-tyric acid was approved in some European countries (Italy and Austria)to treat alcoholism,but more research is needed,consid-ering the risk of gamma-hydroxybutyric acid abuse [55].Amongst other compounds,topiramate,ondansetron,and baclofen seem the most promising pharmacotherapies for alco-holism [56].Topiramate is an anticonvulsant medication,which has demonstrated safety and efficacy in reducing heavy drinking [57].There was also a decrease in liver enzyme levels in patients treated with topiramate [58];however,topiramate has not been tested in patients with ALD.The 5-HT3antagonist ondansetron has been shown to reduce drinking,but this effect was limited to ‘early onset’alcoholics [59].Some studies suggest that baclo-fen,a GABA B receptor agonist,increases abstinence rate and pre-vents relapse in alcohol-dependent patients [60].Moreover,to date,baclofen represents the only alcohol pharmacotherapy tested in alcoholics with significant liver disease.Baclofen may represent a promising pharmacotherapy for alcohol-dependent patients with ALD.A clinical trial demonstrated the safety and efficacy of baclofen in promoting alcohol abstinence in alcoholic cirrhotics patients [61],but confirmatory studies in cirrhotic patients are warranted.The effect of brief interventionsBrief interventions are often performed through motivational interviewing [62].Motivational interviewing is a technique,which aims to be both non-judgmental and non-confrontational.Its success depends largely on the presentation of objective feed-back based on information provided by the physician.The tech-nique involves acknowledgement that individuals who attend a counseling session,assessment or prevention program may be at different levels of readiness to change their alcohol consump-tion patterns.The technique attempts to increase a patient’s awareness of the potential problems caused,consequences expe-rienced,and risks faced as a result of patterns of alcohol consump-tion.A meta-analysis found evidence for the positive impact of brief interventions on alcohol consumption and alcohol related morbidity and mortality [62].The most recent Cochrane review shows that brief interventions are effective to reduce drinking by an average of 57g per week in men [63].Evidence is less con-clusive in women and populations under 16years of age.A brief intervention should at least have the components defined in the five As’model:Ask about use,Advice to quit or reduce,Assess willingness,Assist to quit or reduce and Arrange follow-up.When a motivational component is added to brief interven-tions its efficacy improves [64].Essential components of a moti-vational approach are an empathic attitude and a collaborative approach that respects the patients’autonomy and evoques from them ways to reach the goals agreed.RecommendationsSuggestions for futures studies(1)Collaborative studies by multidisciplinary teams com-posed of epidemiologists,addiction specialists,and hepa-tologists are strongly encouraged.(2)The impact of brief interventions on the prognosis ofadvanced ALD should be evaluated.(3)More studies testing anti-craving drugs in the setting ofadvanced ALD are required.Pathogenesis of ALDThe spectrum of ALD includes simple steatosis,alcoholic steato-hepatitis (ASH),progressive fibrosis,cirrhosis,and the develop-ment of hepatocellular cancer (HCC).Although many individuals consuming more than 60g of alcohol per day (e.g.1/2a bottle of wine or more than 1L of beer)developsteatosis,JOURNAL OF HEPATOLOGYJournal of Hepatology 2012vol.xxx j xxx–xxx5only a minority of the patients with steatosis progress to ASH and 10–20%eventually develop cirrhosis [65].Genetic and non-genetic factors modify both the individual susceptibility and the clinical course of ALD [2].The mechanisms of ALD are not completely understood.Most studies have been performed in rodents with chronic alcohol intake (e.g.Tsukamoto-French model or Lieber–DiCarli diet).However,these models basically induce moderate liver disease and non-severe fibrosis or liver damage develops.Few studies have been performed so far in liv-ers from patients with ALD.These translational studies are needed to develop novel targeted therapies for these patients [2].The pathogenesis varies in different stages of the disease.Alcoholic fatty liverThere are four main pathogenic factors:(1)Increased generation of NADH caused by alcohol oxidation,favouring fatty acid and tri-glyceride synthesis,and inhibiting mitochondrial b -oxidation of fatty acids [66].(2)Enhanced hepatic influx of free fatty acids from adipose tissue and of chylomicrons from the intestinal mucosa [66].(3)Ethanol-mediated inhibition of adenosine monophosphate activated kinase (AMPK)activity [67]resulting in increased lipogenesis and decreased lipolysis by inhibiting per-oxisome proliferating-activated receptor a (PPARa)[68]and stimulating sterol regulatory element binding protein 1c (SREBP1c)[69].(4)Damage to mitochondria and microtubules by acetaldehyde,results in a reduction of NADH oxidation and the accumulation of VLDL,respectively [66].Alcoholic steatohepatitisAlcoholic fatty livers can develop parenchymal inflammation (mainly by PMN cells)and hepatocellular damage,a prerequisite for progress to fibrosis and cirrhosis.In cases of severe ASH epi-sodes in patients with an advanced disease,ASH may cause pro-found liver damage,increased resistance to blood flow and it is also associated with a poor prognosis [70].Various factors may contribute to the development of ASH (1)Acetaldehyde-induced toxic effects.It binds to proteins [71]and to DNA [72]resulting in functional alterations and protein adducts,which activate the immune system by forming autoantigens.It also induces mito-chondria damage and impairs glutathione function,leading to oxi-dative stress and apoptosis [73].(2)Reactive oxygen species (ROS)generation and the resulting lipid peroxidation with DNA adduct formation [74].Main sources of ROS include CYP2E1-dependent MEOS,mitochondrial electron transport system of the respiratory chain,NADH-dependent cytochrome reductase,and xanthine oxi-dase [75,76].Moreover,chronic alcohol intake markedly up-regu-lates CYP2E1,which metabolizes ethanol to acetaldehyde and parallels the generation of ROS and hydroxyl–ethyl radicals [77].(3)Pro-inflammatory cytokines.Alcohol metabolites and ROS stimulate signaling pathways such as NF j B,STAT-JAK,and JNK in hepatic resident cells,leading to the local synthesis of inflam-matory mediators such as TNF a and CXC chemokines (e.g.inter-leukin-8),as well as osteopontin [78].Alcohol abuse also results in changes in the colonic microbiota and increased intestinal per-meability,leading to elevated serum levels of lipopolysaccharides [79]that induce inflammatory actions in Kupffer cells via CD14/TLR4[80].The resulting inflammatory milieu in the alcoholic liver leads to PMN infiltration,ROS formation and hepatocellular damage.(4)Impaired ubiquitin–proteasome pathway leading to hepatocellular injury and hepatic inclusions of aggregated cyto-keratins (i.e.Mallory–Denk bodies)[81].Fibrosis progressionPatients with ASH may develop progressive fibrosis [82].In ALD,the fibrotic tissue is typically located in pericentral and perisinu-soidal areas.In advanced stages,collagen bands are evident and bridging fibrosis develops.This condition precedes the develop-ment of regeneration nodules and liver cirrhosis.The cellular and molecular mechanisms of fibrosis in ALD are not completely understood [83].Alcohol metabolites such as acetaldehyde can directly activate hepatic stellate cells (HSC),the main collagen-producing cells in the injured liver.HSC can also be activated paracrinally by damaged hepatocytes,activated Kupffer cells and infiltrating PMN cells.These cells release fibrogenic media-tors such as growth factors (TGF b 1,PDGF),cytokines (leptin,angiotensin II,interleukin-8,and TNF a ),soluble mediators (nitric oxide),and ROS.Importantly,ROS stimulate pro-fibrogenic intra-cellular signaling pathways in HSC including ERK,PI3K/AKT,and JNK [84].They also up-regulate TIMP-1and decrease the actions of metalloproteinases,thereby promoting collagen accumulation.Cells other than HSC can also synthesize collagen in ALD.They include portal fibroblasts and bone-marrow derived cells.Whether other novel mechanisms such as epithelia-to-mesen-chymal transition of hepatocytes also play a role in liver fibrosis is under investigation [85].Suggestions for futures studies(1)Experimental models of severe ALD with hepatocellulardamage and fibrosis are needed.(2)Translational studies with human samples of patients atdifferent stages of ALD are required to identify new thera-peutic targets.(3)Studies assessing liver regeneration in severe ALD shouldbe performed.Risk factors for disease progression in alcoholic liver disease Risk factors for fibrosis progression in ALD have been evaluated in two types of approaches:(1)comparisons of the prevalence of risk factors in patients with and without fibrotic ALD;(2)lon-gitudinal evaluation using sequential histology.Risk factors for fibrosis progression can be thought of as host and environmental or genetic and non-genetic.Non-genetic or environmental factors that potentially modulate the development of ALD include the amount and type of alcoholic beverage,the duration of abuse and patterns of drinking.Gender,ethnicity,coexisting conditions such as metabolic syndrome,iron overload,and infection with chronic hepatitis viruses are important genetic or host factors,respectively (Fig.1).Increasingly,the contribution of host genetic factors to the risk of ALD is being acknowledged.There is a clear dose-relationship between the amount of alco-hol and the likelihood of developing ALD.Alcoholic steatosis can be found in 60%of individuals who drink >60g of alcohol per day and the risk of developing cirrhosis is highest in those with a daily consumption of above 120g of alcohol per day [86,87].However,lower daily amounts of alcohol may also lead to signif-icant liver injury in some individuals.The consumption of >40gClinical practical guidelines6Journal of Hepatology 2012vol.xxx jxxx–xxx。
肠肝轴定义
肠肝轴定义肠肝轴定义肠肝轴（Gut-liver axis）指的是肠道与肝脏之间相互作用的生理通路。
以下是有关肠肝轴的相关定义及理由，并推荐一本相关书籍：定义一：肠肝轴肠肝轴是指肠道和肝脏之间通过肠道黏膜屏障、肠道微生物群、肠道免疫系统、门静脉系统等多个因素相互作用而形成的一种互动通路。
理由：肠肝轴的研究对于理解肝脏疾病的发生发展机制具有重要意义。
肠道和肝脏密切联系，通过肠道微生物、免疫等途径的调控相互影响，对肝脏健康具有重要的调节作用。
定义二：肠道黏膜屏障肠道黏膜屏障是肠道内部与外界环境之间的一个保护屏障，由黏膜上皮细胞和黏膜下层组织构成。
它起到屏障作用，阻止有害物质的通过，同时保护有益菌群和营养物质的吸收。
理由：肠道黏膜屏障对于肠道和肝脏之间的交流至关重要。
维持肠道黏膜屏障的完整性可以预防肠道内毒素和有害物质的通过，减轻肝脏的负担，并保持肠道内良好的微生物平衡。
定义三：肠道微生物群肠道微生物群是指存在于肠道中的各种微生物的总和。
包括细菌、病毒、真菌和寄生虫等多种微生物。
肠道微生物群对于维持肠道健康、调节免疫功能等具有至关重要的作用。
理由：肠道微生物群与肝脏健康密切相关。
它们通过产生有益代谢产物、调节免疫反应等途径影响肝脏功能。
肠道微生物群失调可能导致肝脏疾病的发生，如脂肪肝、肝纤维化等。
书籍推荐：《肠肝轴：肠道与肝脏的奇妙连接》该书由XXX撰写，系统介绍了肠肝轴的相关概念、研究进展和临床应用。
书中探讨了肠道微生物群、肠道黏膜屏障、免疫系统等因素对肝脏健康的影响，分析了肠肝轴的疾病机制，并提供了相应的治疗策略和预防措施。
本书适合对肠肝轴感兴趣的读者阅读，尤其是医学、生物学和营养学领域的专业人士。
以上是关于肠肝轴定义的列举及相关理由的简要介绍，希望对您有所帮助。
如需了解更多细节，建议阅读上述推荐书籍或参考相关研究文献。
定义四：肠道免疫系统肠道免疫系统是指存在于肠道黏膜屏障中的免疫细胞和免疫分子的集合体。
肠道菌群与酒精性肝病
曼！！里！堡型翌塑！！翌！里！塑型！曼望！璺！鱼！Ｙ型：箜！墅．竺
肠道茵群与酒精性肝病
熊燕鹃，罗和生 武汉大学人民医院消化内科 【摘要】 酒精性肝病（ａｌｃｏｈｏｌｉｃ
消化系统疾病湖北省重点实验室，湖北武汉４３００６０
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ｈｅａｖｙ ｄｒｉｎｋｅｒ，ｆｏｒ ｅｘａｍｐｌｅ，ｔｈｅ ｃｏｍｐｏｓｉｔｉｏｎ ｏｆ ｔｈｅ ｇｕｔ ｍｉｃｒｏｂｉｏｔａ ｉｓ ａｌｔｅｒｅｄ ｗｉｔｈ
ｎｅｇａｔｉｖｅ ｂａｃｔｅｒｉａ ｔｈａｔ ｗｉｌｌ ｌｅａｄ ｔｏ ｅｎｄｏｔｏｘｅｍｉａ ａｎｄ ｏｖｅｒａｃｔｉｖｅ ｉｍｍｕｎｅ
３．１
抗生素饮酒所致的肠道菌群改变主要与胃肠
道细菌大量繁殖有关。 抗生素疗法通过控制大肠细菌过度繁殖来改善 ＡＬＤ的预后。但是，此疗法虽可以改善肝功能，长期
万方数据
宣墅痘堂塑壁痘堂銎查兰Ｑ！垒生竺旦筮兰！鲞筮２塑 使用又会引起肠道菌群再次失衡，引发病原菌的增长。 抗生素的具体选择又需要根据药敏实验的结果，这将 要求过多地使用细胞培养。所以，抗生素疗法应该针 对那些引起ＳＩＢＯ的肠道菌群。 目前认为，利福昔明、羟氨苄青霉素、克拉维酸、甲 硝唑、环丙沙星、诺氟沙星和头孢氨苄这几种抗生素， 在对抗革兰氏阴性需氧菌和产芽孢厌氧菌的过度生长 方面，疗效肯定。近期已有研究‘１引表明，利福昔明在 肝性脑病的治疗中同样有着非常重要的作用，且对于 ＡＬＤ的治疗效果可观。利福昔明最大的优点就是它 不被胃肠道吸收，副作用很少，且耐药发生率 极低‘２０’２ ２Ｉ。
ｉｎｃｒｅａｓｅ ｉｎ ｔｈｅ ｐｒｏｐｏｒｔｉｏｎ ｏｆ Ｇｒａｍ—
肠肝轴ppt课件
3. 抑制肝脏炎症细胞释放的炎症介质，减少肝脏炎症 反应，改善常规肝功能，减少脂质过氧化，保护肝 细胞的功能 。
Carmela Loguercio，et al. Gut-Liver Axis: A New Point of Attack to Treat Chronic Liver Damage? AJG . 2002
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动物实验：VSL#3 probiotics改善非酒精性脂肪肝
control
anti-TNF-a
VSL#3 probiotics
Fig. 1. Effect of anti-TNF antibodies and VSL#3 on hepatic histology of ob/ob mice. (A) ob/ob mice were treated with 4 weeks of control diet (B)control diet plus anti-TNF antibodies,or (C) control diet plus VSL#3 probiotics.
gut microbiota is still a “forgetten organ”, which is remain almost unknown
肠道菌群=“被遗忘的器官”
Sarkis K, et al. Nature. 2008
13
1肠道菌群与肥胖、糖尿病、胰岛素抵 抗
肠道微生物改变胆汁酸结合模式，调节肝 脏和全身脂代谢。分泌肠肽调节游离脂肪 酸形成、吸收和储存。
3
肠道正常菌群
部位
成分
作用
原籍菌 固有的菌群， 厌氧菌：双歧杆菌、类 构成正常菌 杆菌、酪（丁）酸梭菌 群最里层 （科兴 常乐康。。。）
人体器官英语词汇
人体器官英语词汇由多种组织构成的能行使一(特)定功能的结构单位叫做器官。
器官的组织结构特点跟它的功能相适应。
接下来为大家整理了人体器官英语词汇，希望对你有帮助哦!人体器官英语词汇一：head头throat喉咙，咽喉armpit hair腋毛nipple乳头chest胸部pit胸口navel肚脐abdomen腹部private parts阴部thigh大腿neck脖子shoulder肩back背waist腰hip臀部buttock屁股skull颅骨，头盖骨collarbone锁骨rib肋骨backbone脊骨，脊柱shoulder joint肩关节shoulder blade肩胛骨breastbone胸骨elbow joint肘关节pelvis骨盆kneecap膝盖骨bone骨skeleton骨骼sinew腱muscle肌肉joint关节blood vessel血管vein静脉artery动脉capillary毛细血管nerve神经spinal marrow脊髓brain脑人体器官英语词汇二：respiration呼吸windpipe气管lung肺heart心脏diaphragm隔膜exhale呼出inhale呼入internal organs内脏gullet食管stomach胃liver肝脏large intestine大肠blind gut盲肠vermiform appendix阑尾rectum直肠anus肛门bite咬chew咀嚼knead揉捏swallow咽下digest消化absord吸收discharge排泄excrement粪便kidney肾脏bladder膀胱penis阴茎testicles睾丸scroticles阴囊gall bladder胆囊pancreas胰腺spleen脾duodenum12指肠small intestine小肠。
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Gut Liver. 2016 Nov 15;10(6):932-938. doi: 10.5009/gnl15588.
Irritable Bowel Syndrome, Particularly the Constipation-Predominant Form, Involves an Increase in Methanobrevibacter smithii, Which Is Associated with Higher Methane Production.
Ghoshal U1, Shukla R1, Srivastava D2, Ghoshal UC2.
Author information
1
Department of Microbiology, Sanjay Gandhi Postgraduate Institute of Medical
Sciences, Lucknow, India.
2
Department of Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical
Sciences, Lucknow, India.
Abstract
BACKGROUND/AIMS:
Because Methanobrevibacter smithii produces methane, delaying gut transit, we evaluated M. smithii loads in irritable bowel syndrome (IBS) patients and healthy controls (HC).
METHODS:
Quantitative real-time polymerase chain reaction for M. smithii was performed on the feces of 47 IBS patients (Rome III) and 30 HC. On the lactulose hydrogen breath test (LHBT, done for 25 IBS patients), a fasting methane result ≥10 ppm using 10 g of lactulose defined methane-producers.
RESULTS:
Of 47, 20 had constipation (IBS-C), 20 had diarrhea (IBS-D) and seven were not
sub-typed. The M. smithii copy number was higher among IBS patients than HC (Log₁₀5.4, interquartile range [IQR; 3.2 to 6.3] vs 1.9 [0.0 to 3.4], p<0.001), particularly among IBS-C compared to IBS-D patients (Log₁₀6.1 [5.5 to 6.6] vs 3.4 [0.6 to 5.7], p=0.001); the copy number negatively correlated with the stool frequency (R=-0.420, p=0.003). The M. smithii copy number was higher among methane-producers than nonproducers (Log₁₀6.4, IQR [5.7 to 7.4] vs 4.1 [1.8 to 5.8], p=0.001). Using a receiver operating characteristic curve, the best cutoff for M. smithii among methane producers was Log₁₀6.0 (sensitivity, 64%; specificity, 86%; area under curve [AUC], 0.896). The AUC for breath methane correlated with the M. smithii copy number among methane producers (r=0.74, p=0.008). Abdominal bloating was more common among methane producers (n=9/11 [82%] vs 5/14 [36%], p=0.021).
CONCLUSIONS:
Patients with IBS, particularly IBS-C, had higher copy numbers of M. smithii than HC. On LHBT, breath methane levels correlated with M. smithii loads.。