Distinctive aspects of peptic ulcer disease,Dieulafoy'slesion,and Mallory-Weiss syndrome in patients withadvanced alcoholic liver disease or cirrhosis

AIM:To systematically review the data on distinctive aspects of peptic ulcer disease(PUD),Dieulafoy’s lesion(DL),and Mallory-Weiss syndrome(MWS)in patients with advanced alcoholic liver disease(a ALD),including alcoholic hepatitis or alcoholic cirrhosis.METHODS:Computerized literature search performed via Pub Med using the following medical subject heading terms and keywords:"alcoholic liver disease","alcoholic hepatitis","alcoholic cirrhosis","cirrhosis","liver disease","upper gastrointestinal bleeding","nonvariceal upper gastrointestinal bleeding","PUD",‘‘DL’’,‘‘Mallory-Weiss tear",and"MWS’’.RESULTS:While the majority of acute gastrointestinal(GI)bleeding with a ALD is related to portal hypertension,about 30%-40%of acute GI bleeding in patients with a ALD is unrelated to portal hypertension.Such bleeding constitutes an important complication of a ALD because of its frequency,severity,and associated mortality.Patients with cirrhosis have a markedly increased risk of PUD,which further increases with the progression of cirrhosis.Patients with cirrhosis or a ALD and peptic ulcer bleeding(PUB)have worse clinical outcomes than other patients with PUB,including uncontrolled bleeding,rebleeding,and mortality.Alcohol consumption,nonsteroidal anti-inflammatory drug use,and portal hypertension may have a pathogenic role in the development of PUD in patients with a ALD.Limited data suggest that Helicobacter pylori does not play a significant role in the pathogenesis of PUD in most cirrhotic patients.The frequency of bleeding from DL appears to be increased in patients with a ALD.DL may be associated with an especially high mortality in these patients.MWS is strongly associated with heavy alcohol consumption from binge drinking or chronic alcoholism,and is associated with a ALD.Patients with a ALD have more severe MWS bleeding and are more likely to rebleed when compared to non-cirrhotics.Preendoscopic management of acute GI bleeding in patients with a ALD unrelated to portal hypertension is similar to the management of a ALD patients with GI bleeding from portal hypertension,because clinical distinction before endoscopy is difficult.Most patients require intensive care unit admission and attention to avoid over-transfusion,to correct electrolyte abnormalities and coagulopathies,and to administer antibiotic prophylaxis.Alcoholics should receive thiamine and be closely monitored for symptoms of alcohol withdrawal.Prompt endoscopy,after initial resuscitation,is essential to diagnose and appropriately treat these patients.Generally,the same endoscopic hemostatic techniques are used in patients bleeding from PUD,DL,or MWS in patients with a ALD as in the general population.CONCLUSION:Nonvariceal upper GI bleeding in patients with a ALD has clinically important differences from that in the general population without a ALD,including:more frequent and more severe bleeding from PUD,DL,or MWS.

Budd-Chiari syndrome in a patient with ulcerative colitis and no inherited coagulopathy

We report a case of 27 year old female patient who was admitted to the hospital with an acute flare up of ulcerative colitis.The patient presented with complaints of persistent abdominal pain and bloody diarrhea despite aggressive therapy for her ulcerative colitis.A CT scan of the abdomen on admission revealed hepatic vein thrombosis,suggesting a diagnosis of Budd-Chiari syndrome.Significantly,an associated thrombosis of the inferior mesenteric vein was also detected.Based on imaging data and clinical assessment,the patient was started on anticoagulation therapy and an extensive work-up for hypercoagulability was initiated.Up to the time of publication,no significant findings suggesting this patient has an underlying coagulation disorder have been found.Based on our search of PUBMED,this report is one of only five reported adult cases of Budd-Chiari Syndrome associated with ulcerative colitis in the English literature in living patients without evidence of a co-existing coagulation disorder.This case highlights the potential for thrombosis at unusual sites in ulcerative colitis patients even in the absence of classical coagulation abnormalities.In addition to the case presented,we provide a brief review of previously reported cases of Budd-Chiari Syndrome occurring in patients with inflammatory bowel disease.

Chronic ulcerative gastroduodenitis as a first gastrointestinal manifestation of Hermansky-Pudlak syndrome in a 10-year-old child

A 10-year-old Chinese boy who had a history of congenital thrombocytopathy presented with severe iron deficiency anemia secondary to chronic gastric inflammation and duodenal ulcerations. Subtle oculocutaneous albinism led to the finding of diminished dense bodies in the platelets under electron microscopy, hence the diagnosis of Hermansky-Pudlak syndrome (HPS). Biopsies from the stomach and duodenum revealed a lymphocytic infiltration in the submucosa, but H pylori infection was absent. The gastroduodenitis responded to the treatment with omeprazole while iron deficiency anemia was corrected by oral iron therapy. HPS is a rare cause of congenital bleeding disorder with multisystemic manifestations. Upper gastrointestinal involvement is rare and should be distinguished from a mere manifestation of the bleeding diathesis.

Acute respiratory distress syndrome associated with severe ulcerative colitis

Various extraintestinal manifestations including pulmonary abnormalities have been reported in patients with ulcerative colitis. Acute respiratory distress syndrome (ARDS) is a serious and fatal pulmonary manifestation. We have experienced a 67-year-old male patient with ARDS associated with a severe type of ulcerative colitis (UC). Severe dyspnea symptoms occurred during the treatment of UC in a previous hospital and the patient was transferred to our hospital on June 27, 2007. Both blood and sputa cultures for bacteria and fungi were negative. Cytomega-lovirus antigenemia was also not detected. From the clinical and radiological [Chest X-ray, computed tomography (CT)] findings, the patient was diagnosed with ARDS on the basis of the def inition of ARDS developed by the European-American Consensus Conference on ARDS. Both colonic inflammations and ARDS symptoms of the patient were resistant to any medical treatment includingcorticosteroids and antibiotics. However, ARDS symptoms were dramatically improved after surgical colectomy. We believe that severe colonic inflammation from UC was closely associated with the onset of ARDS of the patient. Our case report suggests that a severe type of ulcerative colitis might be taken into consideration as one of the predisposing factors of ARDS.

Epstein–Barr virus-associated hemophagocytic syndrome in a patient with ulcerative colitis during treatment with azathioprine: A case report and review of literature

A 19-year-old female was diagnosed with ulcerative colitis when she presented with persistent melena, and has been treated with 5-aminosalicylic acid for 4 years, with additional azathioprine for 2 years at our hospital. The patient experienced high-grade fevers, chills, and cough fve d prior to presenting to the outpatient unit. At frst, the patient was suspected to have developed neutropenic fever; however, she was diagnosed with Epstein-Barr virus-associated hemophagocytic syndr-ome （EB-VAHS） upon fulfilling the diagnostic criteria after bone marrow aspiration. When patients withinflammatory bowel disease treated with immunomo-dulators, such as thiopurine preparations, develop fever, EB-VAHS should be considered in the differential diagnosis.

Large-vessel thrombosis in intestinal Behet's disease complicated with myelodysplastic syndrome and trisomy 8

Behet's disease is characterized by recurrent oral ulcers, genital ulcers, uveitis and skin lesions. Myelodysplastic syndrome (MDS) is characterized by problems due to ineffective hematopoiesis. Several studies have identified a relationship between MDS and Behet's disease, especially intestinal Behet's disease. Trisomy 8 seems to play an important role in these disorders as well. The present case was a 24-year-old woman who had a huge tonsil ulcer with initial symptoms of odynophagia and intermittent fever. We also noted folliculitis on her upper back. Five days later, she began to experience diarrhea and abdominal pain. Abdominal computed tomography and subsequent surgery revealed ileum perforation and enterocolitis with multiple ulcers. Later, she was admitted again for a vulvar suppurative ulcer and suspicious Bartholin's cyst infection. The patient's clinical presentations met the criteria for Behet's disease. Six months after the bowel perforation event, we noted the development of pancytopenia in a routine laboratory examination. All the examinations led to the diagnosis of MDS with trisomy 8. The most unusual finding was that multiple large vessel thrombi developed during follow-up. Previous studies have suggested that trisomy 8 in MDS leads to concurrent intestinal Behet's disease. Moreover, the inflammatory and immune genes related to thrombus formation are overexpressed in cases of MDS with trisomy 8. Trisomy 8 must play a role in thrombosis. Further studies are needed to help clarify the pathophysiology and pathogenesis of these disorders.

Co-existence of non-alcoholic fatty liver disease and inflammatory bowel disease: a review article

Emerging data have highlighted the co-existence of nonalcoholic fatty liver disease(NAFLD) and inflammatory bowel disease; both of which are increasingly prevalent disorders with significant complications and impact on future health burden. Cross-section observational studies have shown widely variable prevalence rates of co-existing disease,largely due to differences in disease definition and diagnostic tools utilised in the studies. Age,obesity,insulin resistance and other metabolic conditions are common risks factors in observational studies. However,other studies have also suggested a more dominant role of inflammatory bowel disease related factors such as disease activity,duration,steroid use and prior surgical intervention,in the development of NAFLD. This suggests a potentially more complex pathogenesis and relationship between the two diseases which may be contributed by factors including altered intestinal permeability,gut dysbiosis and chronic inflammatory response. Commonly used immunomodulation agents pose potential hepatic toxicity,however no definitive evidence exist linking them to the development of hepatic steatosis,nor are there any data on the impact of therapy and prognosis in patient with co-existent diseases. Further studies are required to assess the impact and establish appropriate screening and management strategies in order to allow early identification,intervention and improve patient outcomes.

Gastrointestinal Behcet's disease:A review

Beh?et's disease(BD) is an idiopathic, chronic, relapsing, multi-systemic vasculitis characterized by recurrent oral and genital aphthous ulcers, ocular disease and skin lesions. Prevalence of BD is highest in countries along the ancient silk road from the Mediterranean basin to East Asia. By comparison, the prevalence in North American and Northern European countries is low. Gastrointestinal manifestations of Beh?et's disease are of particular importance as they are associated with significant morbidity and mortality. Although ileocecal involvement is most commonly described, BD may involve any segment of the intestinal tract as well as the various organs within the gastrointestinal system. Diagnosis is based on clinical criteria- there are no pathognomonic laboratory tests. Methods for monitoring disease activity on therapy are available but imperfect. Evidence-based treatment strategies are lacking. Different classes of medications have been successfully used for the treatment of intestinal BD which include 5-aminosalicylic acid, corticosteroids, immunomodulators, and anti-tumor necrosis factor alpha monoclonal antibody therapy. Like inflammatory bowel disease, surgery is reserved for those who are resistant to medical therapy. A subset of patients have a poor disease course. Accurate methods to detect these patients and the optimal strategy for their treatment are not known at this time.

Gastrointestinal motility and absorptive disorders in patients with inflammatory bowel diseases: Prevalence, diagnosis and treatment

Inflammatory bowel diseases(IBD),Crohns disease and ulcerative colitis,are chronic conditions associated with high morbidity and healthcare costs.The natural history of IBD is variable and marked by alternating periods of flare and remission.Even though the use of newer therapeutic targets has been associated with higher rates of mucosal healing,a great proportion of IBD patients remain symptomatic despite effective control of inflammation.These symptoms may include but not limited to abdominal pain,dyspepsia,diarrhea,urgency,fecal incontinence,constipation or bloating.In this setting,commonly there is an overlap with gastrointestinal(GI)motility and absorptive disorders.Early recognition of these conditions greatly improves patient care and may decrease the risk of mistreatment.Therefore,in this review we describe the prevalence,diagnosis and treatment of GI motility and absorptive disorders that commonly affect patients with IBD.

Diagnosis and management of functional symptoms in inflammatory bowel disease in remission

Inflammatory bowel disease(IBD) patients in remission may suffer from gastrointestinal symptoms that resemble irritable bowel syndrome(IBS). Knowledge on this issue has increased considerably in the last decade, and it is our intention to review and summarize it in the present work. We describe a problematic that comprises physiopathological uncertainties, diagnostic difficulties, as IBS-like symptoms are very similar to those produced by an inflammatory flare, and the necessity of appropriate management of these patients, who, although in remission, have impaired quality of life. Ultimately, from almost a philosophical point of view, the presence of IBS-like symptoms in IBD patients in remission supposes a challenge to the traditional functional-organic dichotomy, suggesting the need for a change of paradigm.

Segmental colitis associated diverticulosis syndrome

Segmental colitis associated diverticulosis(SCAD) has become increasingly appreciated as a form of inflammatory disease of the colon. Several features suggest that SCAD is a distinct disorder. SCAD tends to develop almost exclusively in older adults, predominately, but not exclusively, males. The inflammatory process occurs mainly in the sigmoid colon, and usually remains localized to this region of the colon alone. SCAD most often presents with rectal bleeding and subsequent endoscopic visualization reveals a well localized process with non-specific histopathologic inflammatory changes. Granulomas are not seen, and if present, may be helpful in definition of other disorders such as Crohn's disease of the colon, an entity often confused with SCAD. Bacteriologic and parasitic studies for an infectious agent are negative. Normal rectal mucosa(i.e., "rectal sparing") is present and can be confirmed with normal rectal biopsies. SCAD often resolves spontaneously without treatment, or completely after a limited course of therapy with only a 5-aminosalicylate. Recurrent episodes may occur, but most often, patients with this disorder have an entirely self-limited clinical course. Occasionally, treatment with other agents, including corticosteroids, or surgical resection has been required.

From bench to bedside: Fecal calprotectin in inflammatory bowel diseases clinical setting

Fecal calprotectin(FC) has emerged as one of the most useful tools for clinical management of inflammatory bowel diseases(IBD). Many different methods of assessment have been developed and different cutoffs have been suggested for different clinical settings. We carried out a comprehensive literature review of the most relevant FC-related topics: the role of FC in discriminating between IBD and irritable bowel syndrome(IBS) and its use in managing IBD patients In patients with intestinal symptoms, due to the high negative predictive value a normal FC level reliably rules out active IBD. In IBD patients a correlation with both mucosal healing and histology was found, and there is increasing evidence that FC assessment can be helpful in monitoring disease activity and response to therapy as well as in predicting relapse, post-operative recurrence or pouchitis. Recently, its use in the context of a treat-to-target approach led to a better outcome than clinically-based therapy adjustment in patients with early Crohn's disease. In conclusion, FC measurement represents a cheap, safe and reliable test, easy to perform and with a good reproducibility. The main concerns are still related to the choice of the optimal cut-off, both for differentiating IBD from IBS, and for the management of IBD patients.

Evaluation of bacterial biomarkers to aid in challenging inflammatory bowel diseases diagnostics and subtype classification

BACKGROUND The challenges for inflammatory bowel disease(IBD)diagnostics are to discriminate it from gut conditions with similar symptoms such as irritable bowel syndrome(IBS),to distinguish IBD subtypes,to predict disease progression,and to establish the risk to develop colorectal cancer(CRC).Alterations in gut microbiota have been proposed as a source of information to assist in IBD diagnostics.Faecalibacterium prausnitzii(F.prausnitzii),its phylogroups,and Escherichia coli(E.coli)have been reported as potential biomarkers,but their performance in challenging IBD diagnostic situations remains elusive.We hypothesize that bacterial biomarkers based in these species may help to discriminate these conditions of complex diagnostics.AIM To evaluate the usefulness of indices calculated from the quantification of these species as biomarkers to aid in IBD diagnostics.METHODS A retrospective study of 131 subjects(31 controls(H);45 Crohn’s disease(CD),25 ulcerative colitis(UC),10 IBS,and 20 CRC patients)was performed to assess the usefulness of bacterial biomarkers in biopsies.Further,the performance of biomarkers in faeces was studied in 29 stool samples(19 CD,10 UC).Relative abundances of total F.prausnitzii(FP),its phylogroups(PHGI and PHGII),and E.coli(E)quantification were determined by qPCR.Loads were combined to calculate the FP-E index,the PHGI–E index and the PHGII-E index.Biomarkers accuracy to discriminate among conditions was measured by the area under the receiver operating characteristic curve(AUC).RESULTS In biopsies,FP-E index was good for discriminating IBS from CD(AUC=0.752)while PHGII-E index was suitable for discriminating IBS from UC(AUC=0.632).The FP-E index would be the choice to discriminate IBD from CRC,especially from all UC subtypes(AUC≥0.875),regardless of the activity status of the patient.Discrimination between UC patients that had the longest disease duration and those with CRC featured slightly lower AUC values.Concerning differentiation in IBD with shared location,PHGI-E index can establish progression from proctitis and left-sided colitis to ulcerative pancolitis(AUC≥0.800).PHG I-E index analysis in tissue would be the choice to discriminate within IBD subtypes of shared location(AUC≥0.712),while in non-invasive faecal samples FP or PHGI could be good indicators(AUC≥0.833).CONCLUSION F.prausnitzii phylogroups combined with E.coli offer potential to discriminate between IBD and CRC patients and can assist in IBD subtypes classification,which may help in solving IBD diagnostics challenges.

基于病证结合特点构建寒热错杂型溃疡性结肠炎大鼠模型的实验研究

目的以中医病证结合特点为依据,建立寒热错杂型溃疡性结肠炎(UC)大鼠模型。方法48只SPF级SD大鼠被随机分为空白组、大承气汤组、模型1~4组,每组8只。空白组大鼠正常饲养;大承气汤组以及各模型组大鼠均给予大承气汤灌胃10 d诱导虚寒证,随后采用不同剂量、浓度的2,4,6-三硝基苯磺酸(TNBS)与乙醇的混合液(1∶1)进行UC造模(模型1~4组),建立寒热错杂型UC大鼠模型。考察模型组大鼠的一般状态、寒热错杂表现[体温、粪便含水量、三碘甲状腺原氨酸(T3)及甲状腺素(T4)水平]和UC模型评价指标[疾病活动指数(DAI)、肠质量指数、结肠损伤程度、白细胞介素(IL)-1β、IL-6、IL-4、IL-10、肿瘤坏死因子-α(TNF-α)、髓过氧化物酶(MPO)、超氧化物歧化酶(SOD)、丙二醛(MDA)水平],评价上述模型的有效性。结果与空白组相比,大承气汤组大鼠灌胃10 d后体温显著下降(P<0.01)、粪便含水量显著升高(P<0.01)、血清中T3和T4水平显著下降(P<0.01),提示虚寒证模型成功建立。再继续采用TNBS/乙醇混合液造模后,与大承气汤组相比,模型1~4组大鼠T_(3)和T_(4)水平显著升高(P<0.01),提示寒热错杂模型成功建立。与空白组相比,各模型组大鼠DAI评分、结肠组织形态损伤评分显著升高(P<0.05、P<0.01);其中,模型1组(TNBS剂量70 mg/kg,乙醇体积分数50%)大鼠促炎症细胞因子(IL-1β、TNF-α、IL-6)水平与MPO水平显著升高(P<0.01),抗炎细胞因子(IL-4、IL-10)水平显著降低(P<0.01),提示寒热错杂型UC模型成功建立,且效果最优。结论采用大承气汤诱导虚寒证后,再以TNBS/乙醇联用诱导UC模型,建立了寒热错杂型UC大鼠模型,该模型可广泛应用于相关疾病或药物的实验研究,对于深入了解UC的病理机制、评估中药及其他干预手段的疗效、提高UC精准化治疗的效果具有重要意义。

溃疡性结肠炎中医证候要素及其辨证分型评述

溃疡性结肠炎(ulcerative colitis, UC)是一种主要好发于结直肠的粘膜及粘膜下层、病机未明确、病因复杂、癌变率高的慢性炎症性肠病。中医证候要素是辨证的基本要素,其病位及病性证素是证候辨识的病变本质。文章就UC中医证候要素及其辨证分型作一评述,其证候要素以本虚标实为主要特征,病位证素以大肠、脾、胃、肝、肾为主,病性证素以湿、热、毒、瘀、寒、气滞(郁)、阳虚、阴虚、血虚为主,发病特点是以脾虚为本,湿热瘀毒为标。常见中医证型主要有大肠湿热证、热毒炽盛证、寒热错杂证、肝郁脾虚证、脾胃虚弱证、脾肾阳虚证、阴血亏虚证,其中大肠湿热证最多见。

Intermittent fasting and the liver: Focus on the Ramadan model

Intermittent fasting(IF)is an intervention that involves not only dietary modific-ations but also behavioral changes with the main core being a period of fasting alternating with a period of controlled feeding.The duration of fasting differs from one regimen to another.Ramadan fasting(RF)is a religious fasting for Muslims,it lasts for only one month every one lunar year.In this model of fasting,observers abstain from food and water for a period that extends from dawn to sunset.The period of daily fasting is variable(12-18 hours)as Ramadan rotates in all seasons of the year.Consequently,longer duration of daily fasting is observed during the summer.In fact,RF is a peculiar type of IF.It is a dry IF as no water is allowed during the fasting hours,also there are no calorie restrictions during feeding hours,and the mealtime is exclusively nighttime.These three variables of the RF model are believed to have a variable impact on different liver diseases.RF was evaluated by different observational and interventional studies among patients with non-alcoholic fatty liver disease and it was associated with improve-ments in anthropometric measures,metabolic profile,and liver biochemistry regardless of the calorie restriction among lean and obese patients.The situation is rather different for patients with liver cirrhosis.RF was associated with adverse events among patients with liver cirrhosis irrespective of the underlying etiology of cirrhosis.Cirrhotic patients developed new ascites,ascites were increased,had higher serum bilirubin levels after Ramadan,and frequently developed hepatic encephalopathy and acute upper gastrointestinal bleeding.These complications were higher among patients with Child class B and C cirrhosis,and some fatalities occurred due to fasting.Liver transplant recipients as a special group of patients,are vulnerable to dehydration,fluctuation in blood immunosuppressive levels,likelihood of deterioration and hence observing RF without special precautions could represent a real danger for them.Patients with Gilbert syndrome can safely observe RF despite the minor elevations in serum bilirubin reported during the early days of fasting.

急性主动脉综合征22例误诊分析

目的探讨急性主动脉综合征(AAS)临床特点、误诊原因及防范策略。方法回顾性分析2018年1月至2023年12月收治的曾误诊为其他疾病的AAS 22例。结果22例主要临床表现:心前区撕裂样、压榨性、紧缩性疼痛10例;伴后背痛2例;胸闷、气促5例;单独表现为头晕2例;晕厥发作伴腹部隐痛1例;食欲减退伴乏力1例;头痛、呕吐伴发热1例。误诊为急性冠状动脉综合征11例,其中2例心电图提示ST段特异性改变,同时肌钙蛋白升高,初步诊断为急性心肌梗死;误诊为脑梗死1例;头晕2例误诊为短暂性脑缺血发作;误诊为慢性心功能不全2例,糖尿病酮症酸中毒、慢性阻塞性肺疾病急性加重、痛风、急性左侧心力衰竭、先天性心脏病各1例。误诊时间2 h~6 d。22例均按照误诊疾病予以相应治疗症状未见明显缓解,19例行CT血管造影检查确诊为主动脉疾病,2例经数字减影血管造影确诊,1例经开胸探查确诊。确诊后行相应治疗后19例预后良好,3例死亡。结论AAS病情进展快,早期识别和诊断至关重要。加深临床工作者对此类疾病的认识,提高对该病快速诊断率,及早有效治疗,改善患者预后。

黄颡鱼“溃疡综合征”春季流行的气候特征及预测探讨

为做好黄颡鱼病害早期预警预报,降低鱼病暴发风险,在对2020、2021年湖北黄颡鱼春季病害调查的基础上,对比分析了黄颡鱼病害暴发前及其发生期间天气气候变化特点,提出了病害发病等级标准及鱼病气候胁迫指数的数学计算方法,并对两者统计相关分析;采用秩和检验法、百分位阈值法等方法推算病害等级预测的气候胁迫指标。结果表明:春季降温降水等天气气候急剧变化,造成鱼塘水体低温低氧环境是黄颡鱼病害暴发的催化剂;黄颡鱼病害发生等级DG与气候胁迫指数CSI之间存在显著的相关性(DG=0.215·e^(0.0251×CSI),P<0.001);综合分析得到“溃疡综合征”轻、中、重级发生对应的气候胁迫指标CSI分别为60、80、100。为黄颡鱼春季病害的气象预测提供了基础。

“五辨”诊断思维在溃疡性结肠炎防治中的应用

溃疡性结肠炎是一种反复发作、迁延难愈的消化系统疾病,已经逐渐影响到患者的正常生活,成为临床上难治性疾病之一。近年来中医药在治疗此疾病时不断发挥其优势,得到较好的临床反馈,有望突破治疗瓶颈。中医诊治疾病的两大特征就是辨证论治和整体观念,其中“辨”是中医诊断的基本过程,也是中医临床思维的灵魂。“五辨”,即包括辨病、辨症、辨证、辨人、辨机。将“五辨”诊断思维灵活运用于溃疡性结肠炎的防治中,有助于溃疡性结肠炎内在机制的掌握、发展趋势的判断、特定阶段病理状态的识别、变化规律的把握和矛盾主次的剖析,进而在传统诊治的基础上提供更加有效的理论基础和思路,最终使临床疗效得到提高。

基于网络药理学探究葛根芩连汤异病同治的机制研究

目的本文通过探究葛根芩连汤“一方治三病”的作用机制,“三病”即溃疡性结肠炎、肠易激综合征和2型糖尿病,从实际范例中寻找中医药异病同治理论的应用证据。方法采用网络药理学方法,通过中药系统药理学数据库(Traditional Chinese medicine systems pharmacology database,TCMSP)获取葛根芩连汤的主要活性成分及作用靶点,利用Gene cards、TTD、OMIM数据库获取溃疡性结肠炎、肠易激综合征和2型糖尿病3种疾病的相关靶点。将以上获得的4组靶点取交集获取共同靶点,利用Cytoscape软件绘制“葛根芩连汤-有效成分-共有靶点”网络图;结合STRING数据库绘制PPI网络图,再导入Cytoscape软件进行拓扑分析及可视化。运用Metascape数据库对共有靶点进行基因本体(Gene Ontology,GO)富集分析和京都基因与基因组百科全书(Kyoto encylopedia of genes and genomes,KEGG)通路富集分析。结果筛选并得到葛根芩连汤异病同治溃疡性结肠炎、肠易激综合征、2型糖尿病的共同作用靶点33个。GO富集分析结果显示涉及生物过程20个,主要包括蛋白质磷酸化、炎症反应、细胞凋亡、细胞迁移等。KEGG通路信号分析以P<0.01为显著性水平,发现最小计数为3且富集因子>1.5的通路有15条,包括癌症通路、脂质和动脉粥样硬化通路、晚期糖基化终末产物-糖基化终末产物受体(AGE-RAGE)等通路。结论葛根芩连汤异病同治溃疡性结肠炎、肠易激综合征和2型糖尿病涉及33个共同靶点、20个生物过程及15种信号通路,且在临床应用中均有较好的疗效,可为进一步的实验验证及临床应用提供参考。