食管感觉性受体信号通路在食管高敏感发生中的作用

胃食管反流病（GERD）是一种常见的消化道疾病,烧心和反酸是GERD的典型症状。近年诸多研究显示食管高敏感是烧心症状发生、发展的重要病理生理机制,瞬时受体电位香草酸亚型1(TRPV1)、前列腺素E2受体1 (EP1)、蛋白酶活化受体2(PAR2)、瞬时受体电位M8 (TRPM8)在食管高敏感的发生机制中起关键作用。本文就食管感觉性受体信号通路在食管高敏感发生中的作用作一综述。     

非糜烂性胃食管反流病内脏高敏感机制研究

非糜烂性胃食管反流病(NERD)是指有典型胃食管反流症状而无内镜下食管黏膜损伤的疾病，又称“内镜阴性胃食管反流病”，约占胃食管反流病(GERD)的70％。其临床症状的严重程度与GERD相似，抑酸治疗效果不佳，往往对患者的生活质量产生严重的影响。其发病机制复杂，主要包括酸反流，内脏高敏感，非酸相关性刺激，中枢及外周水平调控失衡等机制。     

胃食管反流病反流症状程度及相关因素的临床分析

胃食管反流病（gastroesophageal reflux disease,GERD）是指胃内容物反流人食管引起不适症状和（或）并发症的一种疾病,包括食管症状（反流症状属于食管症状）以及食管外症状两大类。本研究对轻度和重度反流症状的GERD患者的人口学特征、生活质量、精神心理状态等资料进行了调查,旨在为深人了解GERD并能为临床治疗提供一些帮助。     

胃食管反流病合并情绪障碍的研究现状与诊治策略

胃食管反流病(gastroesophageal reflux disease, GERD)是临床常见的消化系统疾病，机制复杂，情绪障碍在GERD的发生、发展及转归中起到了重要作用，其相互影响的可能机制为：应激导致的脑肠互动异常；情绪障碍可引起某些促炎因子释放及5-HT信号通路紊乱，加重食管免疫炎症及动力异常；迷走神经功能紊乱；食管内脏高敏感；食管及肠道菌群异常。情绪障碍可促进GERD与功能性胃肠病症状重叠，影响GERD药物及抗反流手术的治疗效果。其治疗策略包括：建立互信的医患关系、进行必要的心理干预，重症难治者可使用神经递质药。另外，中医药通过辨证论治，对于治疗该类患者显示出明显优势，未来建立GERD中西医结合防治体系意义重大。     

非糜烂性反流病主要症状发生机制研究进展

非糜烂性反流病（NERD）是胃食管反流病（GERD）的一个亚型,其病理生理学机制复杂且目前对其认识存在争议．直接造成了临床上没有清晰的标准可指导医疗实践。本文重点对NERD主要临床症状的病理生理学机制,如胃十二指肠内容物反流、食管上皮细胞间隙增宽、内脏高敏感．炎症因素、心理因素等作一综述。     

老年人胃食管反流病的治疗

胃食管反流病（GERD）患病率随增龄而增加,老年人是GERD的高危高发人群。老年人GERD治疗的目标是：缓解症状（食管症状及食管外症状）、愈合食管破损黏膜、预防和治疗并发症、防止复发。[第一段]     

食管裂孔疝、胃食管阀瓣与胃食管反流病

胃食管反流病（GERD）是指胃内容物反流入食管,引起不适症状和（或）并发症的一种疾病。GERD患病率国内为5．77％,而国外为7％-15％（亦有高达20％以上者）。近年研究显示,食管裂孔疝（HH）及胃食管阀瓣（GEFV）与GERD发生密切相关。现将HH、GEFV与GERD的关系综述如下。     

5-HT通路异常与胃食管反流病

胃食管反流病（GERD）是胃内容物反流入食管,导致黏膜损伤的一种慢性消化系统疾病,以反流、烧心为主要症状,严重影响人们的生活。长期以来,胃酸对食管黏膜的作用一直作为GERD重要的病理基础,在临床实践中质子泵抑制剂（PPI）一直作为一线的治疗药物,但部分患者对其并不敏感。近年来5-羟色胺（5-HT）代谢通路在胃肠道中的作用日益得到重视。5-HT是与胃肠动力及分泌密切相关的重要神经递质,其代谢通路的异常会导致胃肠道动力的变化及消化道高敏状态。此文将探讨GERD的症状及发病机制与5-HT通路的关系。     

胃食管阀瓣在胃食管反流病中的分布及其与症状的相关性

背景：近年我国胃食管反流病（GERD）的发生率不断升高,胃食管阎瓣（GEFV）分级对评估GERD有重要作用。目的：探讨GEFV在GERD中的分布特征及其与患者症状的关系。方法：选取2010年1～12月聊城市人民医院行胃镜检查发现的343例糜烂性食管炎（EE）、483例非糜烂性反流病（NERD）和99例Barrett食管（BE）患者,记录GEFV的Hill分级,采用GERD症状评定量表（GSAS）记录症状频率、严重度评分。比较GERD各型中GEFV的分布及其与症状频率、严重度评分的关系。结果：异常GEV多见于男性、高龄、超重和食管裂孔疝患者。随着EE的Los Angeles分级增加,异常GEV的发生率增加（P=0.002）;GEFV分级在EE、NERD和BE组间的分布无明显差异（P=0.612）：与正常GEFV组相比,异常GEFV组GERD的症状频率评分明显增高（P〈0.05）,而症状严重度评分无明显差异（P〉0.05）。多重线性回归分析显示症状频率评分与年龄、GEFV分级和GERD类型相关（P〈0.05）,症状严重度评分与年龄、GERD类型相关（P〈0.05）。结论：GEFV分级在GERD各亚型中的分布无明显差异,而与GERD症状频率相关。     

消化内科门诊胃食管反流病诊断问卷诊断胃食管反流病的状况及症状特征分析

目的利用胃食管反流病诊断问卷（Reflux disease questionnaire,RDQ）分析消化专家门诊胃食管反流病（GERD）患病情况及患者症状特征。方法对就诊于我院消化专家门诊的1636例患者进行RDQ问卷调查,得分≥12分者诊断为GERD。根据RDQ内容对GERD患者症状特点进行分析。结果1636例消化专家门诊的患者中,GERD的发生率为10．8％。男女发病无差异（11．0％VS10．5％,P〉0．05）。60岁以上年龄组GERD的患病率最高（14．6％）,而15～30岁年龄组患病率最低（7．7％）。各年龄组内患病率性别间比较差异无显著性。GERD症状中,烧心与反酸为最常见的症状。症状频率积分比严重程度积分更重要（P〈0．05）。结论消化门诊就诊患者GERD患病率较高。GERD患病无性别差异。老年人的GERD患病率高于其他年龄组。烧心和反酸为GERD最常见的症状。症状发生频率比严重程度对GERD的诊断更有意义。     

Esophageal Mast Cell Infiltration in a 32-Year-Old Woman with Noncardiac Chest Pain

Noncardiac chest pain (NCCP) is one of the most common esophageal symptoms and lacks a clearly defined mechanism. The most common cause of NCCP is gastroesophageal reflux disease (GERD). One of the accepted mechanisms of NCCP in a patient without GERD has been altered visceral sensitivity. Mast cells may play a role in visceral hypersensitivity in irritable bowel syndrome. In this case, a patient with NCCP and dysphagia who was unresponsive to proton pump inhibitor treatment had an increased esophageal mast cell infiltration and responded to 14 days of antihistamine and antileukotriene treatment. We suggest that there may be a relationship between esophageal symptoms such as NCCP and esophageal mast cell infiltration.     

Management of the patient with incomplete response to PPI therapy

Proton pump inhibitors (PPIs) remove most of the acid from the gastroesophageal refluxate. However, PPIs do not eliminate reflux and the response of specific GERD symptoms to PPI therapy depends on the degree to which acid drives those symptoms. PPIs are progressively less effective for heartburn, regurgitation, chest pain and extra-oesophageal symptoms. Hence, with an incomplete PPI response, obtaining an accurate history, detailing which symptoms are ‘refractory’ and exactly what evidence exists linking these symptoms to GERD is paramount. Reflux can continue to cause symptoms despite PPI therapy because of persistent acid reflux or weakly acidic reflux. Given these possibilities, diagnostic testing (pH or pH-impedance monitoring) becomes essential. Antireflux surgery is an alternative in patients if a clear relationship is established between persistent symptoms, particularly regurgitation, and reflux. Treating visceral hypersensitivity may also benefit the subset of GERD patients whose symptoms are driven by this mechanism.     

Acupuncture for functional gastrointestinal disorders

Functional gastrointestinal (GI) symptoms are common in the general population. Especially, motor dysfunction of the GI tract and visceral hypersensitivity are important. Acupuncture has been used to treat GI symptoms in China for thousands of years. It is conceivable that acupuncture may be effective in patients with functional GI disorders because it has been shown to alter acid secretion, GI motility, and visceral pain. Acupuncture at the lower limbs (ST-36) causes muscle contractions via the somatoparasympathetic pathway, while at the upper abdomen (CV-12) it causes muscle relaxation via the somatosympathetic pathway. In some patients with gastroesophageal reflux disease (GERD) and functional dyspepsia (FD), peristalsis and gastric motility are impaired. The stimulatory effects of acupuncture at ST-36 on GI motility may be beneficial to patients with GERD or FD, as well as to those with constipation-predominant irritable bowel syndrome (IBS), who show delayed colonic transit. In contrast, the inhibitory effects of acupuncture at CV-12 on GI motility may be beneficial to patients with diarrhea-predominant IBS, because enhanced colonic motility and accelerated colonic transit are reported in such patients. Acupuncture at CV-12 may inhibit gastric acid secretion via the somatosympathetic pathway. Thus, acupuncture may be beneficial to GERD patients. The antiemetic effects of acupuncture at PC-6 (wrist) may be beneficial to patients with FD, whereas the antinociceptive effects of acupuncture at PC-6 and ST-36 may be beneficial to patients with visceral hypersensitivity. In the future, it is expected that acupuncture will be used in the treatment of patients with functional GI disorders.     

Noncardiac chest pain

Noncardiac chest pain (NCCP) affects approximately 1 quarter of the adult population in the United States. The pathophysiology of the disorder remains to be fully elucidated. Identified underlying mechanisms for esophageal pain include gastroesophageal reflux disease (GERD), esophageal dysmotility, and visceral hypersensitivity. Aggressive antireflux treatment has been the main therapeutic strategy for GERD-related NCCP. NCCP patients with or without spastic esophageal motor disorders are responsive to pain modulators. The value of botulinum toxin injection, endoscopic treatment for GERD, and antireflux surgery in alleviating NCCP symptoms is limited.     

食管内脏高敏感及其相关研究进展

胃食管反流疾病(gastroesophageal reflux disease,GERD)是一种较普遍的疾病,经常伴随各种不适症状,需要利用健康护理资源.在动物实验与人类实验研究中均表明,各种传入神经的受体在暴露于酸的情况下均可以敏感化,以至于使更多的感觉刺激通过传入神经输入到脊髓背角神经元,导致了这些神经元的阈值降低,使得他们的感受范围增大.这种敏感性增高的初级传入神经被形容为外周敏感化,而随之增加敏感性的脊髓背角神经元被描述为中央敏感化.一旦这些机制建立起来,可以使组织对以前原本无害的刺激发生敏感,并且会保持一个长期的过程.此外,心理压力和机械刺激都已经被证实可以使细胞间隙增宽,因此可能促进外围敏感化.目前,外围与中枢敏感化被认为是食管疼痛和高敏感的重要机制,甚至生理量的酸亦可以导致症状的发生.对于这些患者的治疗目的主要是降低神经的敏感性.本文主要围绕食管内脏感觉高敏感作一简要综述.     

Refractory GERD: What is it?

Refractory gastroesophageal reflux disease (GERD) is very common and may affect up to 40% of patients who use a proton pump inhibitor (PPI) once daily. Refractory GERD can present as incomplete or lack of response to PPI therapy. The disorder is clearly driven by patients, who present with a wide range of symptom severity and frequency while on PPI treatment. Poor compliance and improper timing of PPI consumption should always be excluded before further evaluation of this patient population. The putative mechanisms for refractory GERD include weakly acidic reflux, duodenogastroesophageal/bile reflux, visceral hypersensitivity, delayed gastric emptying, psychological comorbidity, and concomitant functional bowel disorders. Reduced PPI bioavailability, rapid PPI metabolism, PPI resistance, nocturnal reflux, and Helicobacter pylori infection status have very limited roles in refractory GERD. The contribution of eosinophilic esophagitis to refractory GERD is still unknown. Pill-induced esophagitis, Zollinger-Ellison syndrome, achalasia, and other disorders are rarely responsible for PPI failure and usually are not confused with GERD.     

High Prevalence of Gastroesophageal Reflux Symptoms in Patients with Non-Alcoholic Fatty Liver Disease Associated with Serum Levels of Triglyceride and Cholesterol but Not Simple Visceral Obesity

Background/Aims: Visceral obesity is commonly involved in the pathogenesis of gastroesophageal reflux disease (GERD) and non-alcoholic fatty liver disease (NAFLD). However, other characteristic factors different from visceral obesity are associated with the pathogenesis of NAFLD. We investigated the prevalence of GERD symptoms in patients with NAFLD and its associated risk factors. Methods: NAFLD (n = 96) and controls (n = 139) were enrolled in this study. GERD symptoms were evaluated by using a frequency scale for the symptoms of GERD. Results: GERD symptom score and its prevalence rate were higher in the NAFLD group (7.4 ± 0.7, 37%) than those seen in the control groups (4.5 ± 0.4, 20%), which was independent of sex, age, and body mass index (BMI). GERD symptoms were correlated with insulin resistance (r = 0.167, p = 0.011), total cholesterol (T-CHO) (r = 0.138, p = 0.034), triglyceride (TG) (r = 0.178, p = 0.006), or immunoreactive insulin (r = 0.173, p = 0.008) but not BMI (r = 0.089, p = 0.175). GERD symptoms of the NAFLD group were significantly severer in the higher group of T-CHO and TG levels than those in the lower group. Multivariate analysis proved that risk factors related to GERD symptoms were TG (OR 3.96, 95% CI 1.31-11.9) and T-CHO (OR 3.39, 95% CI 1.11-10.3). Conclusion: The severity and prevalence of GERD symptoms in patients with NAFLD were high, which was associated with serum levels of TG and T-CHO but not BMI.     

Proton pump inhibitor resistance,the real challenge in gastro-esophageal reflux disease

Gastro-esophageal reflux disease(GERD)is one of the most prevalent chronic diseases.Although proton pump inhibitors(PPIs)represent the mainstay of treatment both for healing erosive esophagitis and for symptom relief,several studies have shown that up to 40%of GERD patients reported either partial or complete lack of response of their symptoms to a standard PPI dose once daily.Several mechanisms have been proposed as involved in PPIs resistance,including ineffective control of gastric acid secretion,esophageal hypersensitivity,ultrastructural and functional changes in the esophageal epithelium.The diagnostic evaluation of a refractory GERD patients should include an accurate clinical evaluation,upper endoscopy,esophageal manometry and ambulatory pH-impedance monitoring,which allows to discriminate non-erosive reflux disease patients from those presenting esophageal hypersensitivity or functional heartburn.Treatment has been primarily based on doubling the PPI dose or switching to another PPI.Patients with proven disease,not responding to PPI twice daily,are eligible for anti-reflux surgery.     

Gastroesophageal reflux disease: Update on inflammation and symptom perception

Although gastroesophageal reflux disease(GERD)is a common disorder in Western countries,with a significant impact on quality of life and healthcare costs,the mechanisms involved in the pathogenesis of symptoms remain to be fully elucidated.GERD symptoms and complications may result from a multifactorial mechanism,in which acid and acid-pepsin are the important noxious factors involved.Prolonged contact of the esophageal mucosa with the refluxed content,probably caused by a defective anti-reflux barrier and luminal clearance mechanisms,would appear to be responsible for macroscopically detectable injury to the esophageal squamous epithelium.Receptors on acid-sensitive nerve endings may play a role in nociception and esophageal sensitivity,as suggested in animal models of chronic acid exposure.Meanwhile,specific cytokine and chemokine profiles would appear to underlie the various esophageal phenotypes of GERD,explaining,in part,the genesis of esophagitis in a subset of patients.Despite these findings,which show a significant production of inflammatory mediators and neurotransmitters in the pathogenesis of GERD,the relationship between the hypersensitivity and esophageal inflammation is not clear.Moreover,the large majority of GERD patients(up to 70%)do not develop esophageal erosions,a variant of the condition called non-erosive reflux disease.This summary aims to explore the inflammatory pathway involved in GERD pathogenesis,to better understand the possible distinction between erosive and non-erosive reflux disease patients and to provide new therapeutic approaches.