肠道微生态影响动脉粥样硬化发生发展的机制

动脉粥样硬化(AS)不仅是一种炎症性疾病,而且属于一种代谢性疾病。肠道微生态的改变可对AS的发生发展产生双面影响。一方面,肠道菌群紊乱可以通过影响机体的胆碱代谢、氧化应激、炎症反应等机制直接促进AS产生发展,此外,可通过导致AS危险因素肥胖、高脂血症、糖尿病等的产生这些间接机制促AS的进展。另一方面,益生菌及益生元的增加则可有效地降低肠道微生物内毒素产生、增强肠道屏障、减轻机体质量、缓解炎症反应、改善胰岛素抵抗,进而在AS的进展方面发挥重要作用。因此,合理调控机体肠道微生态环境成为AS防治的新型重要手段。     

PNPLA3 I148M polymorphism and progressive liver disease

The 148 Isoleucine to Methionine protein variant(I148M)of patatin-like phospholipase domain-containing 3(PNPLA3),a protein is expressed in the liver and is involved in lipid metabolism,has recently been identified as a major determinant of liver fat content.Several studies confirmed that the I148M variant predisposes towards the full spectrum of liver damage associated with fatty liver:from simple steatosis to steatohepatitis and progressive fibrosis.Furthermore,the I148M variant represents a major determinant of progression of alcohol related steatohepatitis to cirrhosis,and to influence fibrogenesis and related clinical outcomes in chronic hepatitis C virus hepatitis,and possibly chronic hepatitis B virus hepatitis,hereditary hemochromatosis and primary sclerosing cholangitis.All in all,studies suggest that the I148M polymorphism may represent a general modifier of fibrogenesis in liver diseases.Remarkably,the effect of the I148M variant on fibrosis was independent of that on hepatic steatosis and inflammation,suggesting that it may affect both the quantity and quality of hepatic lipids and the biology of non-parenchymal liver cells besides hepatocytes,directly promoting fibrogenesis.Therefore,PNPLA3 is a key player in liver disease progression.Assessment of the I148M polymorphism will possibly inform clinical practice in the future,whereas the determination of the effect of the 148M variant will reveal mechanisms involved in hepatic fibrogenesis.     

瓣膜性房颤定义及抗凝治疗研究进展

现阶段对于"瓣膜病变型"房颤(AF)与"非瓣膜病变型"AF的定义尚未达成共识,不仅如此,各指南在表述这些概念时也存在差异。临床试验对于"瓣膜病变型"AF与"非瓣膜病变型"AF定义的阐述不甚理想。两类AF血栓栓塞风险差异较大,抗凝治疗策略也有所不同。本文将对瓣膜性AF定义及抗凝治疗的研究进展予以综述。     

Endoscopic resection techniques for colorectal neoplasia:Current developments

Endoscopic polypectomy and endoscopic mucosal resection(EMR) are the established treatment standards for colorectal polyps. Current research aims at the reduction of both complication and recurrence rates as well as on shortening procedure times. Cold snare resection is the emerging standard for the treatment of smaller(< 5 mm) polyps and is possibly also suitable for the removal of noncancerous polyps up to 9 mm. The method avoids thermal damage, has reduced procedure times and probably also a lower risk for delayed bleeding. On the other end of the treatment spectrum, endoscopic submucosal dissection(ESD)offers en bloc resection of larger flat or sessile lesions. The technique has obvious advantages in the treatment of high-grade dysplasia and early cancer. Due to its minimal recurrence rate, it may also be an alternative to fractionated EMR of larger flat or sessile lesions. However, ESD is technically demanding and burdened by longer procedure times and higher costs. It should therefore be restricted to lesions suspicious for high-grade dysplasia or early invasive cancer.The latest addition to endoscopic resection techniques is endoscopic fullthickness resection with specifically developed devices for flexible endoscopy.This method is very useful for the treatment of smaller difficult-to-resect lesions,e.g., recurrence with scar formation after previous endoscopic resections.     

Lymph node staging in colorectal cancer:Old controversies and recent advances

Outcome prediction based on tumor stage reflected by the American Joint Committee on Cancer(AJCC)/Union for International Cancer Control(UICC)tumor node metastasis(TNM)system is currently regarded as the strongest prognostic parameter for patients with colorectal cancer.For affected patients,the indication for adjuvant therapy is mainly guided by the presence of regional lymph node metastasis.In addition to the extent of surgical lymph node removal and the thoroughness of the pathologist in dissecting the resection specimen,several parameters that are related to the pathological work-up of the dissected nodes may affect the clinical significance of lymph node staging.These include changing definitions of lymph nodes,involved lymph nodes,and tumor deposits in different editions of the AJCC/UICC TNM system as well as the minimum number of nodes to be dissected.Methods to increase the lymph node yield in the fatty tissue include methylene blue injection and acetone compression.Outcome prediction based on the lymph node ratio,defined as the number of positive lymph nodes divided by the total number of retrieved nodes,may be superior to the absolute numbers of involved nodes.Extracapsular invasion has been identified as additional prognostic factor.Adding step sectioning and immunohistochemistry to the pathological work-up may result in higher accuracy of histological diagnosis.The clinical value of more recent technical advances,such as sentinel lymph node biopsy and molecular analysis of lymph nodes tissue still remains to be defined.     

Acute kidney injury spectrum in patients with chronic liver disease:Where do we stand?

Acute kidney injury (AKI) is a common complication of liver cirrhosis and is of the utmost clinical and prognostic relevance. Patients with cirrhosis, especially decompensated cirrhosis, are more prone to develop AKI than those without cirrhosis. The hepatorenal syndrome type of AKI (HRS–AKI), a spectrum of disorders in prerenal chronic liver disease, and acute tubular necrosis (ATN) are the two most common causes of AKI in patients with chronic liver disease and cirrhosis. Differentiating these conditions is essential due to the differences in treatment. Prerenal AKI, a more benign disorder, responds well to plasma volume expansion, while ATN requires more specific renal support and is associated with substantial mortality. HRS–AKI is a facet of these two conditions, which are characterized by a dysregulation of the immune response. Recently, there has been progress in better defining this clinical entity, and studies have begun to address optimal care. The present review synopsizes the current diagnostic criteria, pathophysiology, and treatment modalities of HRS–AKI and as well as AKI in other chronic liver diseases (non-HRS–AKI) so that early recognition of HRS–AKI and the appropriate management can be established.     

Prophecy about post-endoscopic retrograde cholangiopancreatography pancreatitis:From divination to science

One unresolved issue of endoscopic retrograde cholangiopancreatography(ERCP)is post-ERCP pancreatitis (PEP),which occurs in up to 40%of patients.Identification of risk factors for PEP is especially important in the field of ERCP practice because it may assist physicians in taking protective measures in situations with high risk.A decade ago,Freeman et al meticulously evaluated a large number of potentially relevant risk factors for PEP,which can be divided into patient-relat-ed and procedure-related issues.In this commentary, we summarize this classic article and reevaluate the risk factors for PEP from the current point of view.This is followed by assessment of strategies for prevention of PEP that can be divided into mechanical and pharmacologic methods.     

Role of endoscopic ultrasound in the screening and follow-up of high-risk individuals for familial pancreatic cancer

Managing familial pancreatic cancer(FPC)is challenging for gastroenterologists,surgeons and oncologists.High-risk individuals(HRI)for pancreatic cancer(PC)(FPC or with germline mutations)are a heterogeneous group of subjects with a theoretical lifetime cumulative risk of PC over 5%.Screening is mainly based on annual magnetic resonance imaging(MRI)and endoscopic ultrasound(EUS).The goal of screening is to identify early-stage operable cancers or high-risk precancerous lesions(pancreatic intraepithelial neoplasia or intraductal papillary mucinous neoplasms with high-grade dysplasia).In the literature,target lesions are identified in 2%-5%of HRI who undergo screening.EUS appears to provide better identification of small solid lesions(0%-46%of HRI)and chronicpancreatitis-like parenchymal changes(14%-77%of HRI),while MRI is probably the best modality to identify small cystic lesions(13%-49%of HRI).There are no specific studies in HRI on the use of contrast-enhanced harmonic EUS.EUS can also be used to obtain tissue samples.Nevertheless,there is still limited evidence on the accuracy of imaging procedures used for screening or agreement on which patients to treat.The cost-effectiveness of screening is also unclear.Certain new EUS-related techniques,such as searching for DNA abnormalities or protein markers in pancreatic fluid,appear to be promising.     

Issues and controversies in esophageal inlet patch

The proximal esophagus is rarely examined,and its inspection is often inadequate.Optical chromoendoscopy techniques such as narrow band imaging improve the detection rate of inlet patches in the proximal esophagus,a region in which their prevalence is likely underestimated.Various studies have reported correlations between these esophageal marks with different issues such as Barrett’s esophagus,but these findings remain controversial.Conflicting reports complicate the process of interpreting the clinical features of esophageal inlet patches and underestimate their importance.Unfortunately,the limited clinical data and statistical analyses make reaching any conclusions difficult.It is hypothesized that inlet patches are correlated with various esophageal and extraesophageal symptoms,diagnoses and the personalized therapeutic management of patients with inlet patches as well as the differential diagnosis for premalignant lesions or early cancers.Due to its potential underdiagnosis,there are no consensus guidelines for the management and follow up of inlet patches.This review focuses on questions that were raised from published literature on esophageal inlet patches in adults.     

Sleep,immunity and inflammation in gastrointestinal disorders

Sleep disorders have become a global issue,and discovering their causes and consequences are the focus of many research endeavors.An estimated 70 million Americans suffer from some form of sleep disorder.Certain sleep disorders have been shown to cause neurocognitive impairment such as decreased cognitive ability,slower response times and performance detriments.Recent research suggests that individuals with sleep abnormalities are also at greater risk of serious adverse health,economic consequences,and most importantly increased all-cause mortality.Several research studies support the associations among sleep,immune function and inflammation.Here,we review the current research linking sleep,immune function,and gastrointestinal diseases and discuss the interdependent relationship between sleep and these gastrointestinal disorders.Different physiologic processes including immune system and inflammatory cytokines help regulate the sleep.The inflammatory cytokines such as tumor necrosis factor,interleukin-1(IL-1),and IL-6 have been shown to be a significant contributor of sleep disturbances.On the other hand,sleep disturbances such as sleep deprivation have been shown to up regulate these inflammatory cytokines.Alterations in these cytokine levels have been demonstrated in certain gastrointestinal diseases such as inflammatory bowel disease,gastro-esophageal reflux,liver disorders and colorectal cancer.In turn,abnormal sleep brought on by these diseases is shown to contribute to the severity of these same gastrointestinal diseases.Knowledge of these relationships will allow gastroenterologists a great opportunity to enhance the care of their patients.     

功能性消化不良患者胃感觉运动功能的研究

目的 探讨胃感觉运动功能障碍在功能性消化不良(FD)患者中的表现和相互关系。方法 用单光子放射计算机断层成像(SPECT)和内脏刺激器／电子气压泵检测22例FD患者和20例健康对照者的胃固体排空、胃敏感性、胃顺应性和近端胃容受性。结果 22例FD患者胃排空延迟、胃敏感性增高和近端胃容受性障碍的发生率分别为31．8％，68．2％和45．5％，其中45.5％的患者出现了两种以上的胃感觉运动功能障碍。三种胃感觉运动功能障碍间无相关关系(P＞0．05)。结论 胃排空延迟、胃敏感性增高及近端胃容受性障碍是FD发病中三种相互独立的重要因素，不同的病理生理异常可在同一FD患者中共存。     

Carcinogenic Action of 2,7-Diacetylaminofluorene on the Stomach of Rats with Experimental Gastric Ulcer

Penetrating ulcers of gastric glandular mucosa were produced in male Buffalo rats by thermocautery. These rats, and uninjured control animals, were fed with a diet containing a known carcinogen, 2,7 diacetylaminofluorene (2,7-DAAF). The purpose of this study was to find whether the presence of gastric ulcer will enhance the incidence of gastric carcinoma. In 14% of rats in which gastric ulcers were associated with the exposure to oral carcinogen, gastric adenocarcinomas were found. No gastric tumors were diagnosed in rats having uninjured gastric mucosas prior to the ingestion of carcinogen. It is concluded that the contact of chemical carcinogen 2,7-DAAF with injured, healing gastric mucosa, enhanced the malignant transformation of gastric cellular elements. Under the conditions of this experiment, the presence of gastric ulcer contributed to the appearance of gastric adenocarcinoma.     

The electrophoretic pattern of normal human gastric juice and of the gastric juice of patients with gastric ulcer and gastric cancer

This study reports the electrophoretic pattern of the proteins in human gastric juice of control patients and patients with gastric ulcer and gastric carcinoma. Autodigestion was prevented by intragastric neutralization. The statistical limits of normal are defined and the changes found in the gastric juice of gastric ulcer and gastric patients with gastric carcinoma described.     

Comprehensive Gastric Emptying Study for Type-II Diabetes Mellitus Dyspeptic Patients

Background: Gastrointestinal symptoms without demonstrable lesions in the upper gastrointestinal tract are common in diabetic patients. Scintigraphic liquid- and solid-phase gastric emptying studies and gastric emptying of indigestible particles were performed to determine the gastric emptying function in type-II diabetes mellitus patients with dyspepsia. Methods: Twenty type-II diabetic patients with symptoms suggestive of delayed gastric emptying were included. A gelatin capsule containing 10 rod-shaped radiopaque markers was ingested, along with the solid-phase test meal, to assess the emptying of indigestible particles. Scintigraphic liquid-phase gastric emptying studies were performed on a separate day. Results: There were 7 patients (35%) with delayed liquid-phase gastric emptying, 14 patients (70%) with delayed solid-phase gastric emptying, and 14 patients (70%) with abnormal gastric emptying of indigestible particles. There were only three patients (15%) with normal gastric emptying of both the liquid and solid phase. Furthermore, only one patient showed normal results in all three gastric emptying studies. Conclusions: For determining abnormalities in gastric emptying function for type-II diabetic dyspepsia patients, comprehensive gastric emptying studies, including scintigraphic liquid- and solid-phase gastric emptying studies and gastric emptying of indigestible particles, are most helpful.     

Gastric juice nitrite and vitamin C in patients with gastric cancer and atrophic gastritis: is low acidity solely responsible for cancer risk?

BACKGROUND: N-nitroso compounds are carcinogens formed from nitrite, a process that is inhibited by vitamin C in gastric juice. Helicobacter pylori infection has been reported to increase nitrite and decrease vitamin C in gastric juice. Therefore, susceptibility to gastric cancer in H. pylori-infected patients may be derived from increased N-nitroso compounds in gastric juice. However, most H. pylori-infected patients do not develop gastric cancer. OBJECTIVE: To investigate additional factors that may affect susceptibility to gastric cancer, we compared nitrite and vitamin C levels in gastric juice from H. pylori-infected patients with and without gastric cancer. METHODS: Serum and gastric juice were obtained from 95 patients undergoing diagnostic endoscopy, including those with normal findings, duodenal ulcer, gastric ulcer, atrophic gastritis and gastric cancer. Serum was analysed for H. pylori antibody, nitrate and nitrite, gastrin and pepsinogens; gastric juice was analysed for pH, nitrite and vitamin C. RESULTS: pH and nitrite levels were increased and vitamin C levels decreased in the gastric juice of patients with atrophic gastritis and gastric cancer compared with other patients. However, in patients with a similar gastric acidity (pH 5-8), nitrite concentrations in the gastric juice were significantly higher and vitamin C levels significantly lower in patients with gastric cancer than in those with atrophic gastritis. CONCLUSION: Although hypochlorhydria increases intraluminal nitrite and decreases intraluminal vitamin C, which increases the intraluminal formation of N-nitroso compounds, our results indicate that patients with gastric cancer may have additional factors that emphasize these changes.     

The detection of an antigen present in gastric carcinoma

Studies to detect antigenic sulfoglycoproteins using indirect immunofluorescence and counterimmunoelectrophoresis were performed on thirty-two gastric biopsies and on thirty-six gastric aspirations, respectively. Patients with gastric carcinoma, lymphoma, benign gastric lesions, and patients without evidence of gastric disease were studied. Specific antisera to sulfoglycoproteins found in aspirates of gastric carcinoma patients were produced in rabbits and later absorbed to increase specificity. Fluorescent staining of the cell membrane was observed in tissues of gastric carcinoma patients. In biopsies from patients with other forms of gastric pathology as well as normal gastric mucosa, a more diffuse fluorescent staining was noted. Counterimmunoelectrophoresis demonstrated a single precipitin band in all aspirates from patients with gastric carcinoma, in one patient with lymphoma, and in one patient with gastric polyps showing atypical hyperplasia. The remaining aspirates produced no precipitin bands. Results of this study suggest that counterimmunoelectrophoresis has greater diagnostic value than the indirect immunofluorescent technique for the detection of gastric sulfoglycoproteins. Thus, counterimmunoelectrophoresis may prove useful in the diagnosis of gastric carcinoma.This study was supported by United States Public Health Service Grant Number HL-5278.     

胃液紫外光吸收光谱对胃癌诊断价值的初步探讨

目的 探讨胃液高效液相紫外光吸收光谱诊断胃癌的价值。方法 以市郊和液相方法分析了１４４例胃内良恶性病变患者的胃液并以紫外光检测器检测，其中进展其胃癌３７例，萎缩性胃炎３０例，消化性溃疡３０例，慢性浅表性胃炎４７例。结果 进展期胃癌与胃内良性病变患者胃液的高效液相紫外光吸收光谱明显不同，胃癌患者峰位数明显多于胃内良性病变患者，这表明进展期胃癌与胃内良性病变患者胃液的成分明显存在差异。经单因素方差分析     

Basal and somatostatin-stimulated gastric intraluminal prostaglandin E2 in patients with gastric ulcer and with gastric adenocarcinoma

The effect of somatostatin-14 (SST), at doses utilized in clinical practice, on gastric intraluminal prostaglandin (PG) E2 release was evaluated in 8 endoscopically normal subjects, in 6 patients with benign gastric ulcer and in 8 patients with gastric adenocarcinoma. In normal subjects, SST induced a significant increase in gastric intraluminal PGE2 concentration and output, whereas it did not augment the concentration and output of PGE2 in patients with gastric ulcer and with gastric cancer. The altered PG response to SST stimulation shown by gastric ulcer and gastric cancer patients may be related to a modified cell population in the gastric mucosa and/or to a defective regulation of this local gastric mucosal mediator.     

Control of gastric emptying by gastric tone

During ingestion of food, the stomach relaxes to accommodate the meal and, subsequently, a progressive gastric contraction parallels gastric emptying. Intestinal nutrients trigger feedback relaxatory mechanisms that regulate gastric tone and, hence, the nutrient load delivered into the small intestine. This regulation of gastric tone is mediated, at least in part, via the vagus. Defective gastric tone is associated with impaired gastric emptying, as seen in patients with postsurgical gastroparesis. However, increased intragastric pressure, corresponding with defective gastric accommodation, induces abdominal symptoms, but does not alter the gastric emptying pattern. These data indicate that gastric emptying is controlled by complementary mechanisms: gastric tone exerts an emptying force, but gastric outlet resistance is also an important regulator.