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.     

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.     

1-磷酸鞘胺醇受体3参与巨噬细胞迁移及脓毒症诱导的心肌损伤

目的探讨巨噬细胞中1-磷酸鞘胺醇受体(sphingosine 1-phosphate receptor,S1PR)的表达及其作用,观察干预S1PR3(S1P3)对脂多糖诱导的心肌损伤的影响。方法传代培养小鼠Ana-1巨噬细胞,给予脂多糖(lipopolysaccharide,LPS,100 ng/ml)刺激或S1P3特异性抑制剂CAY-10444(10μmol/L)干预,细胞随机分为对照组、LPS组、CAY-10444组、CAY-10444预处理2h+LPS组,Transwell小室观测巨噬细胞迁移,蛋白免疫印迹检测巨噬细胞S1PR的表达,并检测p-Akt/Akt蛋白水平。在体实验,6~8周龄雄性C57/B6小鼠,随机分为对照组、LPS组、CAY-10444组、CAY-10444干预+LPS组,每组12只,LPS(10 mg/kg)腹腔注射,或CAY-10444 1 mg/kg于LPS诱导后30 min腹腔注射干预,24 h后取心脏组织HE染色观察病理改变,免疫组化染色观察巨噬细胞浸润程度以及炎症因子的表达情况,实时荧光定量PCR检测心肌损伤标记分子BNP、巨噬细胞表面分子F4/80、炎症因子TNF-α、IL-1β、IL-6的mRNA水平。结果与对照组比较,LPS诱导巨噬细胞大量迁移S1P3蛋白表达增加(P0.01),p-Akt Ser473/Akt表达上调(P0.01);与LPS组相比,S1P3抑制剂CAY-10444干预后再给予LPS刺激,巨噬细胞迁移被抑制(P0.01),p-Akt Ser473/Akt表达也降低(P0.01);在体实验,LPS诱导小鼠后BNP mRNA水平明显上调(P0.01),同时F4/80以及炎症因子TNF-α、IL-1β、IL-6的mRNA水平上调(P0.01),HE染色可见心肌损伤及炎细胞浸润,免疫组化染色法显示F4/80及炎症因子的大量阳性表达(P0.01);使用S1P3抑制剂后,与LPS组比较,心肌损伤减轻免疫组化中巨噬细胞减少(P0.01),炎症因子表达降低(P0.01),BNP mRNA水平降低(P0.01),F4/80以及TNF-α、IL-1β、IL-6的mRNA水平也明显降低(P0.01)。结论抑制巨噬细胞S1P3表达可抑制巨噬细胞的迁移并提示p-Akt/Akt与了这一过程,此外,S1P3抑制剂的干预可有效减轻LPS诱导的心肌损伤。     

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.     

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.     

游离神经移植修复周围神经缺损100例

目的 探讨自体腓肠神经等感觉神经游离移植修复四肢神经缺损。方法 对100例外伤所致四肢神经缺损者根据神经缺损部位及游离移植神经长度。分别用带血管的神经游离移植和单纯的神经游离移植。神经供区：腓肠神经(87例)、臂内侧皮神经(6例)、前臂内侧皮神经(1例)、前臂外侧皮神经(2例)、腓浅神经(2例)、隐神经(2例)。结果术后随访71例(85条神经)。随访时间18～60个月，其中优(M4S3 )13例(14条)．良(M3S3)22例(26条)。可(M2S2)32例(40条)，差(M1S1以下)4例(1条)。结论 用自体神经移植修复四肢神经缺损，可有效恢复损伤神经．对肢体的功能恢复仍有较为满意的效果。     

自主神经系统在心房颤动中的作用和联系

心房颤动（房颤）在临床上极为常见,目前心房颤动的机制尚未阐明,其中自主神经系统在房颤的发生、维持、终止和决定室性心律上是一个潜在的强大的调节因素。存在于中枢、神经节、外周组织、细胞和亚细胞水平的交感和副交感系统的复杂相互作用都能够改变心脏的传导性和不应期,较为重要的是分布于心脏的自主神经的调节作用能引起心房节律的改变以及影响触发活动的产生和类型,所有这些变化都能引发和维持房颤。本文就心脏自主神经系统在房颤发生发展过程中的可能的作用机制及相互联系作一综述,为基础研究和临床实践中对房颤的机制研究和治疗提供参考依据和理论基础。     

斯氏狸殖吸虫体壁神经细胞与神经纤维的观察

目的　探讨斯氏狸殖吸虫的体壁神经细胞和神经纤维的分布特点和相互间关系。方法　采用乙酰胆碱酯酶定位技术对斯氏狸殖吸虫的神经细胞和神经纤维进行显示。结果　斯氏狸殖吸虫前部体壁内神经纤维密集 ,以纵行神经纤维为主 ,虫体中部以相互交叉的斜行神经纤维为主。斯氏狸殖吸虫有两类神经细胞 ,即双极和多极神经细胞 ;虫体前部的纵行神经纤维上以多极神经细胞分布较多 ,中部较少 ,后部最少。双级神经细胞分布于神经节内、神经干内过神经干旁。在虫体的横截面上 ,神经细胞位于神经纤维下。结论　斯氏狸殖吸虫的前部体壁神经纤维密集 ,多极神经细胞较多 ,可能与虫体前部肌活动能力强有密切关系。     

美托洛尔对急性心肌梗死大鼠心肌神经生长因子表达和神经重构的影响

目的 探讨β受体阻滞剂美托洛尔对大鼠急性心肌梗死(AMI)后心肌神经生长因子(NGF)表达和交感神经再生的影响.方法 结扎大鼠左前降支,建立AMI模型,存活者随机分为美托洛尔治疗组(MI-B组,n=10)和梗死对照组(MI-C组,n=10),另设假手术组(S组,n=8).MI-B组给予4周美托洛尔治疗,MI-C组和S组给予同体积生理盐水静脉注射和灌胃,4周后检测梗死周边区和梗死远端心脏神经纤维分布和密度以及心肌NGF基因和蛋白表达的变化.结果 与S组相比,MI-C组梗死周边和梗死远端心肌组织中NGF基因和蛋白表达明显升高(P＜0.05),梗死周边和梗死远端神经支配密度增高(P＜0.01).与MI-C组比较,MI-B组心肌细胞内NGF表达明显下降(P＜0.05),神经支配密度亦明显下降(P＜0.01).结论 早期美托洛尔治疗AMI可以改善心肌NGF表达和交感神经再生.美托洛尔改善交感神经再生的作用机制至少部分与其降低神经生长因子的表达和释放作用有关.     

神经生长因子及其受体在人胰腺导管癌组织中的表达

目的 探讨β神经生长因子(β-NGF)及其受体[酪氨酸激酶A(tyrosine kinase A,TrKA)和P75NGFR]在人胰腺导管癌组织中的表达及意义.方法 选择胰腺导管癌组织标本80例和正常胰腺组织20例,采用免疫组化、荧光定量PCR等方法,定量检测β-NGF及其受体表达,分析β-NGF)及其受体与临床病理学特征,尤其与神经侵袭的关系.结果 随着癌细胞分化程度降低和肿瘤TNM分期增加,β-NGF、TrKA蛋白表达水平增加,且低分化与高分化、中分化组相比显著增加(P<0.01),Ⅲ～Ⅳ期较Ⅰ～Ⅱ期显著增加(P<0.05);β-NGF、TrKA蛋白表达水平在有神经浸润组明显高于无神经浸润组(P<0.01),有淋巴结转移组明显高于无淋巴结转移组(P<0.01),且邻近神经组织的肿瘤细胞β-NGF、TrKA阳性程度高于远离神经组织的癌细胞.P75NGFR表达与肿瘤细胞分化程度关系密切.β-NGF和TrKA表达呈正相关.β-NGF、TrKA和P75NGFR mRNA表达水平在胰腺癌组织中明显高于正常胰腺组织,分别增加3.84、4.23和2.41倍.结论 β-NGF及其受体参与介导胰腺癌的发生,与胰腺癌临床病理学特征关系密切,β-NGF、TrKA高表达和胰腺癌嗜神经性关系密切.     

燃煤污染型砷中毒患者的神经电生理检测

目的　评价燃煤型慢性砷中毒患者的神经系统损害。方法　随机检测 5 1例患者的肌电图 ,运动神经传导速度 (MCV) ,感觉神经传导速度 (SCV) ,F波 ,H反射 ,体感诱发电位 (SEP)。结果　 12 0块肌肉肌电图6 6 .7%以多相不规则波为主 ;MCV与 SCV均有减慢 ,以 SCV减慢最为显著 ,而 MCV远端动作电位潜伏期明显延长 ,神经传导速度 (NCV )的异常远比纤颤、正尖波检出率高 ,且随病情的加重改变愈加明显 ;F波与 H反射异常率不高 ,提示很少累及神经根 ;SEP的异常率高达 6 0 .8% ,同时说明该组患者伴有中枢神经的损害。结论　神经电生理检测可以用来观察燃煤污染型慢性砷中毒患者的神经系统损害程度、病程、范围 ,亦是该病的早期检查手段之一     

Nerve conduction in diabetic pregnancy. A prospective study

Repeated neurographic examinations were performed during and after the pregnancies of 32 diabetic women who had no signs of neuropathy before pregnancy or at the initial examination during the first trimester. The motor conduction velocity, the sensory conduction velocity and the peak amplitude of the compound action potential of the investigated peripheral nerves were not affected by pregnancy. It is concluded that pregnancy does not impair nerve conduction or induce neuropathy in most diabetic women.     

神经生长因子及其受体在人胰腺导管癌组织中的表达

Objective To investigate nerve growth factor (β-NGF) and its receptors expression in human pancreatic ductal adenocarcinoma. Methods Expression and distribution of β-NGF, tyrosine kinase A (TrKA) and P75NGFR were detected in operation tissue specimens of pancreatic ductal adenocarcinoma with immunohistochemistry and real-time PCR. Relations of β-NGF and its receptors with clinicalpathological characters, especially nerve invasion were analyzed. Results β-NGF and TrKA expression are higher in pancreatic adenocarcinoma than normal pancreas, and the differences are significant (P < 0. 01). Β-NGF and TrKA expression are associated with the differentiation grades(DG), lymphatic node metastasis, nerve invasion and surgical pathological stages. Poorer of DG and later stages, more expression of β-NGF and TrKA. Β-NGF and TrKA expression have positive correlations. Β-NGF, TrKA and P75NGFR mRNA expression have significantly increased 3.84,4. 23 and 2. 41 times than normal tissues by real-time PCR, respectively. Conclusions β-NGF and TrKA might play potential rules in carcinogenesis for pancreatic cancer,have affinity with clinicopathological characters of pancreatic cancer. Β-NGF and TrKA may have mutual effect in signal transduction leading to perineural invasion of pancreatic carcinoma.     

神经生长因子及其受体在人胰腺导管癌组织中的表达

Objective To investigate nerve growth factor (β-NGF) and its receptors expression in human pancreatic ductal adenocarcinoma. Methods Expression and distribution of β-NGF, tyrosine kinase A (TrKA) and P75NGFR were detected in operation tissue specimens of pancreatic ductal adenocarcinoma with immunohistochemistry and real-time PCR. Relations of β-NGF and its receptors with clinicalpathological characters, especially nerve invasion were analyzed. Results β-NGF and TrKA expression are higher in pancreatic adenocarcinoma than normal pancreas, and the differences are significant (P < 0. 01). Β-NGF and TrKA expression are associated with the differentiation grades(DG), lymphatic node metastasis, nerve invasion and surgical pathological stages. Poorer of DG and later stages, more expression of β-NGF and TrKA. Β-NGF and TrKA expression have positive correlations. Β-NGF, TrKA and P75NGFR mRNA expression have significantly increased 3.84,4. 23 and 2. 41 times than normal tissues by real-time PCR, respectively. Conclusions β-NGF and TrKA might play potential rules in carcinogenesis for pancreatic cancer,have affinity with clinicopathological characters of pancreatic cancer. Β-NGF and TrKA may have mutual effect in signal transduction leading to perineural invasion of pancreatic carcinoma.