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。     

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。     

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.     

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.     

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.     

外援PCI与转运PCI对于急性心肌梗死救治的影响

目的探讨转运经皮冠状动脉介入(PCI)治疗与外援PCI对急性心肌梗死(AMI)救治的影响。方法收集经外援PCI方式(输送医生)救治的AMI患者50名以及经转运PCI方式(转运患者)救治的AMI患者50名的资料。比较两种救治方式对于决定介入至导管室(determine intervention to catheter room,DI-to-C)时间、决定介入至球囊扩张(determine intervention to balloon dilation,DI-to-B)时间、完全血运重建率、急性期住院病死率及随访6个月主要不良心血管事件(MACE)发生率的影响。结果两组总的转运路程为35~100 km,车程约40~90 min。外援PCI组DI-to-C、DI-to-B时间与转运PCI组无显著差别,但外援PCI组的完全血运重建率、急性期住院并发症率好于转运PCI组(P0.05),两组的随访6个月的MACE发生率也有显著差异(P0.05)。结论跟目前成熟的转运PCI相比,外援PCI无法缩短DI-to-C、DI-to-B时间,但在提高血运重建率、降低急性期住院并发症、改善预后方面有积极的意义。     

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.     

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.     

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.     

Endoscopic management of difficult common bile duct stones

Endoscopy is widely accepted as the first treatment option in the management of bile duct stones.In this review we focus on the alternative endoscopic modalities for the management of difficult common bile duct stones.Most biliary stones can be removed with an extraction balloon,extraction basket or mechanical lithotripsy after endoscopic sphincterotomy.Endoscopic papillary balloon dilation with or without endoscopic sphincterotomy or mechanical lithotripsy has been shown to be effective for management of difficult to remove bile duct stones in selected patients.Ductal clearance can be safely achieved with peroral cholangioscopy guided laser or electrohydraulic lithotripsy in most cases where other endoscopic treatment modalities have failed.Biliary stenting may be an alternative treatment option for frail and elderly patients or those with serious co morbidities.     

Obstructive sleep apnea increases heart rhythm disorders and worsens subsequent outcomes in elderly patients with subacute myocardial infarction

OBJECTIVE Obstructive sleep apnea(OSA)is a potential cardiovascular risk.We aimed to investigate the association of OSA with heart rhythm disorders and prognosis in elderly patients with new-onset acute myocardial infarction(AMI).METHODS We prospectively enrolled 252 AMI elderly patients(mean age,68.5±6.9 years)who were undergoing revascularization and completed a sleep study during their hospitalization.All subjects were categorized into non-OSA(apnea–hypopnea index(AHI)<15,n=130)and OSA(AHI≥15,n=122)groups based on the AHI.The changes in the autonomic nervous system,incidence of arrhythmia during nocturnal sleep,and major adverse cardiovascular and cerebrovascular events(MACCEs)were compared between the groups.RESULTS The mean AHI value in all AMI patients was 22.8±10.9.OSA patients showed higher levels of body mass index and peak high-sensitivity C-reactive protein and lower levels of minimum nocturnal oxygen saturation(Min Sa O2),as well as greater proportion of multivessel coronary artery disease(all P<0.05).The OSA group also showed significant increases in heart rate variability and heart rate turbulence onset(both P<0.05)and higher incidence of arrhythmia(including sinus,atrial,and ventricular in origin).At a median follow-up of 6 months(mean 0.8–1.6 years),OSA(AHI≥15)combined with hypoxia(Min Sa O2≤80%)was independently associated with the incidence of MACCEs(hazard ratio[HR]:4.536;95%confidence interval[CI]:1.461-14.084,P=0.009)after adjusting for traditional risk factors.CONCLUSIONS OSA and OSA-induced hypoxia may correlate with the severity of myocardial infarction,increase the occurrence of heart rhythm disorders in elderly subacute MI patients,and worsen their short-term poor outcomes.     

Endoscopy and polyps-diagnostic and therapeutic advances in management

Despite multiple efforts aimed at early detection through screening, colon cancer remains the third leading cause of cancer-related deaths in the United States, with an estimated 51000 deaths during 2013 alone. The goal remains to identify and remove benign neoplastic polyps prior to becoming invasive cancers. Polypoid lesions of the colon vary widely from hyperplastic, hamartomatous and inflammatory to neoplastic adenomatous growths. Although these lesions are all benign, they are common, with up to one-quarter of patients over 60 years old will develop pre-malignant adenomatous polyps. Colonoscopy is the most effective screening tool to detect polyps and colon cancer, although several studies have demonstrated missed polyp rates from 6%-29%, largely due to variations in polyp size. This number can be as high as 40%, even with advanced (> 1 cm) adenomas. Other factors including sub-optimal bowel preparation, experience of the endoscopist, and patient anatomical variations all affect the detection rate. Additional challenges in decision-making exist when dealing with more advanced, and typically larger, polyps that have traditionally required formal resection. In this brief review, we will explore the recent advances in polyp detection and therapeutic options.     

Rare cystic liver lesions: A diagnostic and managing challenge

Cystic formations within the liver are a frequent finding among populations.Besides the common cystic lesions,like simple liver cysts,rare cystic liver lesions like cystadenocarcinoma should also be considered in the differential diagnosis.Thorough knowledge of each entity’s nature and course are key elements to successful treatment.Detailed search in PubMed,Cochrane Database,and international published literature regarding rare cystic liver lesions was carried out.In our research are included not only primary rare lesions like cystadenoma,hydatid cyst,and polycystic liver disease,but also secondary ones like metastasis from gastrointestinal stromal tumors lesions.Up-to date knowledge regarding diagnosis and management of rare cystic liver lesions is provided.A diagnostic and therapeutic algorithm is also proposed.The need for a multidisciplinary approach by a team including radiologists and surgeons familiar with liver cystic entities,diagnostic tools,and treatment modalities is stressed.Patients with cystic liver lesions must be carefully evaluated by a multidisciplinary team,in order to receive the most appropriate treatment,since many cystic liver lesions have a malignant potential and evolution.     

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.     

Effects of N-3 Fatty Acids on the Coronary Heart Disease Patients

Objectives To evaluate the effects of n-3 fatty acids on the coronary heart disease patients. Methods From September 2007 to March 2008, 60 patients with coronary heart disease were randomly assigned to n-3 fatty acids group (group N) and control group (group C). Both groups received standard coronary artery disease secondary prevention treatment and group N also received eicosapentaenoic acid (EPA) 1.8 g plus docosahexaenoic acid (DHA) 1.2 g per day for 12 weeks. Plasma triacylglycerols, total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and blood pressure were measured before and after the study. Results Plasma triacylglycerols, blood pressure and LDL-C level were lower in group N after n-3 fatty acids treatment while no change was found in group C (P<0.05). HDL-C level slightly increased and total cholesterol level slightly decreased after n-3 fatty acids but both change were not significant (P>0.05). Conclusions N-3 fatty acids have beneficial effects on the coronary artery disease patients.     

Recent standardization of treatment strategy for pancreatic neuroendocrine tumors

Recent advances in localization techniques,such as the selective arterial secretagogue injection test(SASI test) and somatostatin receptor scintigraphy have promoted curative resection surgery for patients with pancreatic neuroendocrine tumors(PNET).For patients with sporadic functioning PNET,curative resection surgery has been established by localization with the SASI test using secretin or calcium.For curative resection of functioning PNET associated with multiple endocrine neoplasia type 1(MEN 1) which are usually multiple and sometimes numerous,resection surgery of the pancreas and/or the duodenum has to be performed based on localization by the SASI test.As resection surgery of PNET has increased,several important pathological features of PNET have been revealed.For example,in patients with Zollinger-Ellison syndrome(ZES),duodenal gastrinoma has been detected more frequently than pancreatic gastrinoma,and in patients with MEN 1 and ZES,gastrinomas have been located mostly in the duodenum,and pancreatic gastrinoma has been found to co-exist in 13% of patients.Nonfunctioning PNET in patients with MEN 1 becomes metastatic to the liver when it is more than 1 cm in diameter and should be resected after careful observation.The most important prognos-tic factor in patients with PNET is the development of hepatic metastases.The treatment strategy for hepatic metastases of PNET has not been established and aggressive resection with chemotherapy and trans-arterial chemoembolization have been performed with significant benefit.The usefulness of octreotide treatment and other molecular targeting agents are currently being assessed.     

Calculation of left ventricular diastolic time constant(Tau) in dogs with aortic regurgitation using continuous-wave Doppler spectra

OBJECTIVE To investigate a new noninvasive method for calculating left ventricular diastolic time constant(Tau) through a continuous-wave aortic regurgitation Doppler spectrum.METHODS According to ultrasound guidance, twenty-four animal models(beagles) of aortic regurgitation and acute ischemic left ventricular diastolic dysfunction were created. The left ventricular diastolic function was manipulated with dobutamine or esmolol and fifty-nine hemodynamic stages were achieved. Raw audio signals of the continuous-wave Doppler spectra were collected, and new aortic regurgitation Doppler spectra were built after reprocessing by a personal computer. The updating time of the spectral line was 0.3 ms. The new Doppler spectra contour line was automated using MATLAB(MATrix LABoratory, MathWorks, Natick, MA, USA), and two time intervals,(t2–t1) and(t3–t1) were measured on the ascending branch of the aortic regurgitation Doppler spectrum. Then, the two time intervals were substituted into Bai's equations, and Doppler-derived Tau(Tau-D)was resolved and compared with catheter-derived Tau(Tau-c).RESULTS There is no significant difference between Tau-D and Tau-c(45.95 ± 16.90 ms and 46.81 ± 17.31 ms, respectively;P >0.05). Correlation analysis between Tau-c and Tau-D suggested a strong positive relationship(r = 0.97, P = 0.000). A Bland-Altman plot of Tau-c and Tau-D revealed fair agreement.CONCLUSIONS This new calculation method is simple, convenient, and shows a strong positive relationship and fair agreement with the catheter method.     

Outcomes of cardiac surgery in senior aged patients with ventricular dysfunction:analysis of a large national database

OBJECTIVE In patients undergoing cardiac surgery,reduced preoperative ejection fraction(EF)and senior age are associated with a worse outcome.As most outcome data available for these patients are mainly from Western surgical populations involving specific surgery types,our aim is to evaluate the real-world characteristics and perioperative outcomes of surgery in senior-aged heart failure patients with reduced EF across a broad range cardiac surgeries.METHODS Data were obtained from the China Heart Failure Surgery Registry(China-HFSR)database,a nationwide multicenter registry study in China's Mainland.Multiple variable regression analysis was performed in patients over 75 years old to identify risk factors associated with mortality.RESULTS From 2012 to 2017,578 senior-aged(>75 years)patients were enrolled in China HFSR,21.1%of whom were female.Isolated coronary bypass grafting(CABG)were performed in 71.6%of patients,10.1%of patients underwent isolated valve surgery and 8.7%received CABG combined with valve surgery.In-hospital mortality was 10.6%,and the major complication rate was 17.3%.Multivariate analysis identified diabetes mellitus(odds ratio(OR)=1.985),increased creatinine(OR=1.007),New York Heart Association(NYHA)Class III(OR=1.408),NYHA class IV(OR=1.955),cardiogenic shock(OR,6.271),and preoperative intra-aortic balloon pump insertion(OR=3.426)as independent predictors of in-hospital mortality.CONCLUSIONS In senior-aged patients,preoperative evaluation should be carefully performed,and strict management of reversible factors needs more attention.Senior-aged patients commonly have a more severe disease status combined with more frequent comorbidities,which may lead to a high risk in mortality.     

No evidence of HPV DNA in esophageal squamous cell carcinoma in a population of Southern Brazil

AIM:To investigate the association between human papillomavirus(HPV)and esophageal squamous cell carcinoma(ESCC)in southern Brazil.METHODS:We studied 189 esophageal samples from125 patients from three different groups:(1)102 biopsies from 51 patients with ESCC,with one sample from the tumor and another from normal esophageal mucosa distant from the tumor;(2)50 esophageal biopsies from 37 patients with a previous diagnosis of head and neck squamous cell carcinoma(HNSCC);and(3)37 biopsies from esophageal mucosa with normal appearance from 37 dyspeptic patients,not exposed to smoking or alcohol consumption.Nested-polymerase chain reaction(PCR)with the MY09/11 and GP5/6 L1primers was used to detect HPV L1 in samples fixed in formalin and stored in paraffin blocks.All PCR reactions were performed with a positive control(cervicovaginal samples),with a negative control(Human Genomic DNA)and with a blank reaction containing all reagents except DNA.We took extreme care to prevent DNA contamination in sample collection,processing,and testing.RESULTS:The histological biopsies confirmed the diagnosis of ESCC in 52 samples(51 from ESCC group and 1 from the HNSCC group)and classified as well differentiated(12/52,23.1%),moderately differentiated(27/52,51.9%)or poorly differentiated(7/52,13.5%).One hundred twenty-eight esophageal biopsies were considered normal(51 from the ESCC group,42 from the HNSCC group and 35 from dyspeptic patients).Nine had esophagitis(7 from the HNSCC and 2 from dyspeptic patients).Of a total of 189 samples,only 6 samples had insufficient material for PCR analysis:1 from mucosa distant from the tumor in a patient with ESCC,3from patients with HNSCC and 2 from patients without cancer.In 183 samples(96.8%)GAPDH,G3PDH and/orβ-globin were amplified,thus indicating the adequacy of the DNA in those samples.HPV DNA was negative in all the 183 samples tested:52 with ESCC,9 with esophagitis and 122 with normal esophageal mucosa.CONCLUSION:There was no evidence of HPV infection in different ESCC from southern Br