胃食管反流病患者食管上皮Occludin的表达及细胞间隙的改变

目的:研究胃食管反流病(GERD)患者食管上皮细胞紧密连接蛋白Occludin表达的变化及食管上皮细胞间隙的改变.方法:采用免疫组织化学法检测62例GERD患者[其中反流性食管炎(RE组)患者30例,非糜烂性反流病(NERD组)患者32例]及10例正常对照食管下段上皮的紧密连接蛋白Occludin表达,并在光镜下观察切片并采集图像,采用图像分析系统对每例切片测量100个细胞间隙,进行统计学分析.结果:10例正常对照组Occludin呈正常连续的细胞膜表达,NERD组4例正常表达,28例不同程度异常表达,为细胞膜不完整表达、细胞质表达及表达缺失,30例RE均表达异常;RE组和NERD组Occludin阳性率与正常对照组比较,差异均有显著性(p<0.01),而RE组与NERD组间比较,无显著差异.RE组和NERD组平均细胞间隙与正常对照组比较,均有显著性差异(1.51±0.31μm,1.38±0.26μm vs 0.77±0.12 μm,均P<0.01),而RE组和NERD组间无显著差异.结论:胃食管反流病患者食管上皮Occludin数量减少、分布异常,导致细胞间隙增宽,影响黏膜上皮屏障的完整性,可能是胃食管反流病的发病机制之一.     

非糜烂性反流病与反流性食管炎酸袋情况比较及相关性探讨

目的通过对非糜烂性反流病(NERD)与反流性食管炎(RE)酸袋情况的研究比较,探讨NERD及RE相关性。方法 15名健康志愿者和59例胃食管反流病(GERD)患者参与本研究。根据胃镜下食管黏膜是否损伤将GERD患者分为NERD组及RE组。对所有受试者进行食管测压、酸袋检测及食管24 h动态pH监测。根据是否存在食管异常酸反流进一步分为食管异常酸反流阴性NERD(n-NERD)组、食管异常酸反流阳性NERD(p-NERD)组、食管异常酸反流阴性RE(n-RE)组及食管异常酸反流阳性RE(p-RE)组。比较各组间酸袋情况。结果各组间酸袋发生率无统计学意义。n-NERD组酸袋持续时间最短,与n-RE组及p-RE组比较有统计学意义(P<0.05)。p-RE组酸袋平均pH值最低,与健康组、n-NERD组及p-NERD组比较有统计学意义(P<0.05)。进一步比较发现n-NERD组较RE组酸袋出现时间晚,持续时间短,平均pH值高(P<0.05)。p-NERD组仅酸袋平均pH值较RE组高(P<0.05)。结论 n-NERD与p-NERD并非单纯为NERD的两种异常酸反流不同的情况。p-NERD与RE有更多相似性,似乎为RE黏膜损伤前状态。     

胃食管反流病患者食管动力及酸暴露特点分析

目的通过对胃食管反流病(gastroesophageal reflux disease,GERD)患者食管高分辨率测压及24 h食管p H-阻抗联合监测结果分析,以探讨GERD患者食管动力及酸暴露特点.方法选取2017-07/2018-07就诊于石河子大学第一附属医院消化内科门诊及住院部具有典型症状(反酸、烧心)、根据蒙特利尔共识意见可诊断为GERD的患者59例,行胃镜、食管高分辨率测压及24 h食管p H-阻抗联合监测等检查;根据胃镜是否诊断反流性食管炎(reflux esophagitis, RE)组(27例,男/女:12/15)和非糜烂性反流病(nonerosive reflux disease, NERD)组(32例,男/女:14/18),比较两组患者食管高分辨测压及24 h食管pH-阻抗监测结果的差异.结果食管高分辨率测压结果中, RE组患者下食管括约肌静息压明显低于NERD组(P0.05),上食管括约肌静息压及上下食管括约肌残余压比较差异无统计学意义(P0.05), RE组患者远端波波幅低于NERD组(P 0.05),蠕动波持续时间、起始速度、远端收缩延迟时间两组间差异无统计学意义(P0.05);分析24 h食管pH-Z监测结果, RE组DeMeester评分明显高于NERD组(P0.05),总计酸反流时间低于NERD组(P 0.05),立卧位反流次数、总计反流次数、不同物理性质之间差异无统计学意义(P0.05).结论不同GERD患者食管动力及酸反流存在一定的差异,RE患者食管动力障碍及酸反流较NERD更明显.     

人食管上皮酸反流损伤的早期超微结构改变

学改变.本研究的目的是确定此种改变是否也是人食管酸反流损伤的一种早期表现.方法用透射电镜检查10例正常对照组,12例胃食管反流病(GERD)患者(经24 h pH监测和压力测定诊断为GERD)的内镜活检标本(标本均取自食管下端5 cm内、内镜下无异常的粘膜),用图象分析仪测量每例标本透射电镜照片的细胞间隙.结果胃食管反流病患者组的细胞间隙(1.27±0.77)μm大于正常对照组细胞间隙(0.49±0.08)μm,P＜0.01,前者有9例有细胞间隙≥2.5 μm,而正常对照组无一例有细胞间隙≥2.5μm.结论细胞间隙增大是人食管酸反流损伤的一种早期表现.     

NERD患者症状与食管鳞状上皮细胞间隙关系的研究

背景:通过光学显微镜可发现非糜烂性反流病(NERD)患者存在食管鳞状上皮细胞间隙增宽(DIS),但关于不同症状与DIS的研究少见。目的:研究NERD患者症状与食管鳞状上皮细胞间隙之间的关系。方法:选取40例通过内镜检查和质子泵抑制剂试验诊断为NERD的患者,按照症状分为反流组、烧心组和胸痛组,同时选取10名健康志愿者作为对照。行胃镜检查和HE染色,测量光镜下平均细胞间隙(LMIS)。NERD患者同时行症状评分,并分析与LMIS的关系。结果:NERD组LMIS明显高于健康对照组[(1.38±0.43)μm对(0.45±0.07)μm;t=4.47,P=0.00]。反流组、烧心组和胸痛组之间LMIS差异有统计学意义(F=177.89,P<0.01),烧心组、胸痛组又明显高于反流组[(1.46±0.73)μm、(1.45±0.49)μm对(1.34±0.41)μm;P=0.00,P=0.00]。反流组、烧心组和胸痛组LMIS与症状评分之间均呈正相关(r=0.925,P<0.01;r=0.919,P<0.01;r=0.922,P<0.01)。结论:DIS是NERD对食管上皮组织损伤的一种微观变化,与NERD症状发生相关,烧心和胸痛患者DIS变化更为明显。     

食管远端鳞状上皮细胞间隙增宽对非糜烂性反流病诊断的价值

目的:研究非糜烂性反流病(NERD)食管远端鳞状上皮细胞间隙变化及与食管酸暴露、反流症状严重程度的关系,探讨细胞间隙增宽对NERD诊断的价值.方法:纳入NERD患者(66例)和正常对照者(38例).所有受试者行GerdQ调查、食管24hpH值监测、胃镜检查并在食管齿状线(Z线)和Z上2cm线位置取活检,透射电镜测量鳞状上皮细胞间隙;pH监测阴性NERD患者行质子泵抑制剂诊断试验确诊.结果:(1)NERD组Z线和Z线上2cm的平均细胞间隙分别为(0.90±0.11)μm、(0.92±0.16)μm,正常对照组分别为(0.65±0.08)μm、(0.67±0.08)μm,两组间差异有统计学意义(P<0.05),组内差异无统计学意义(P>0.05);(2)NERD患者Z线和Z线上2cm两部位pH(+)亚组与pH(-)亚组的细胞间隙比较,差异均无统计学意义(P>0.05);GerdQ(+)亚组与GerdQ(-)亚组的细胞间隙比较,差异也均无统计学意义(P>0.05);(3)Z线和Z线上2cm两部位的平均细胞间隙与DeMeester积分均呈正相关性,r分别为0.33(P=0.001)、0.35(P=0.001);与GerdQ评分也均呈正相关性,r分别为0.32(P=0.006)、0.45(P<0.001);(4)Z线平均细胞间隙的cut-off值为0.81μm时,约登指数最大(0.808),诊断的敏感度为80.8%,特异度为100.0%.Z线上2cm平均细胞间隙的cut-off值为0.81μm时,约登指数最大(0.731),诊断的敏感度为75.8%,特异度为97.4%.结论:NERD食管远端鳞状上皮细胞间隙明显增宽,细胞间隙与食管远端胃酸暴露和反流症状的严重程度呈正相关.细胞间隙增宽可作为NERD诊断的一种敏感客观结构指标.     

不同类型胃食管反流病发病机制的差异

目的:比较不同类型胃食管反流病(GERD),即反流性食管炎(RE)、非糜烂性反流病(NERD)和Barrett食管(BE)发病机制的差异.方法:113例GERD患者,根据内镜下表现及病理情况分为RE、NERD、BE三组,比较三组患者内镜下表现、食管测压和24 h pH监测指标、合并食管裂孔疝(HH)情况的差异.结果:RE组较NERD组与BE组下食管括约肌压力减低,但无统计学差异.食管体部各段的收缩波幅比较,RE组减低最明显,NERD组减低最少,两组比较P<0.05;无效食管运功比较,RE组较另两组明显增多( P<0.05).RE、NERD、BE组24 h食管pH监测的DeMeester计分分别为90.2、55.2、48.8;RE组以重度酸暴露多见(43%),反流总时间阳性率较高;NERD组以轻度酸暴露多见(45.8%),反流频率阳性率较高;BE组以长反流时间阳性率较高.HH在RE、NERD、BE组中的检出率分别为50%、14.6%、25.7%( P = 0.003).结论:下食管括约肌及食管体部运动功能受损程度、酸反流情况的差异可能是造成三种不同类型GERD食管黏膜损伤表现不同的主要原因.     

共聚焦激光显微内镜对非糜烂性反流病微观变化的诊断价值

目的探讨非糜烂性反流病(NERD)患者电镜下微观结构的改变,研究食管下端黏膜的微观变化及其与反流的关系,为NERD的诊断及治疗提供依据。方法选取具有烧心、反酸≥3个月、反流性疾病问卷(RDQ)≥12分的患者纳入本研究。据内镜下表现将无黏膜破损者定为NERD患者组。选择同期的健康志愿者作为对照组。用共聚焦激光显微内镜(CLE)测量上皮乳头内毛细血管襻(IPCLs)数目、直径及鳞状上皮细胞间隙等,并与病理学资料相比较。同时行24 h食管多通道腔内阻抗-pH监测。按照反流物的组成成分(液体、混合及气体反流)及反流物的pH值(酸、弱酸及无酸反流)分别分析。结果共有67例患者纳入CLE检查,其中NERD患者46例[平均年龄(48.9±13.6)岁,男24例,女22例],对照者21例[平均年龄(35.0±12.3)岁,男11例,女9例]。NERD组IPCLs的数目、直径(μm)均大于对照组(8.29±3.52 vs 5.69±2.31,P=0.010)(19.48±3.13 vs 15.87±2.21,P=0.041),对于鳞状上皮细胞间隙,NERD组的平均值(μm)明显大于对照组(3.40±0.82 vs 1.90±0.53,P=0.042);ROC曲线显示两组间IPCLs数目的最佳工作点为6.0/FOV(AUC 0.722,95%CI:0.592~0.853),IPCLs直径的最佳工作点为17.20μm(AUC0.847,95%CI:0.747~0.947),细胞间隙的最佳工作点为2.40μm(AUC 0.935,95%CI:2.895~0.995)。IPCLs数目增多、扩张与存在DIS诊断NERD的敏感性最高,为100%。酸反流与IPCLs数目增多(β=0.059,t=2.017,P=0.030)及IPCLs扩张(β=0.047,t=2.236,P=0.045)有关。按照体位分析,则以卧位下明显,酸反流与IPCLs数目增多和扩张的β值、t值及P值分别为0.063、2.895、0.038和0.156、1.023、0.040。Bland-Altman plot分析结果显示CLE与透射电镜测得的细胞间隙数值有良好的一致性。结论CLE可清晰地观察到食管黏膜IPCLs形态、管径的变化及细胞间隙增宽,CLE在体测得的DIS与透射电镜一致,CLE可以作为快速、方便诊断NERD微观变化的实用工具。     

反流性食管炎及非糜烂性胃食管反流病超微结构比较

目的研究反流性食管炎与非糜烂性胃食管反流病（NERD）超微结构的特点。方法随机选取反流性疾病诊断问卷调查评分（Sc）在12分以上的13例患者，经胃镜检查7例诊断反流性食管炎（A组），6例诊断NERD（B组），两组患者均取食管病理组织行透射电镜检查，其中7例患者行食管测压和24h食管pH监测检查。结果反流性疾病诊断问卷提示A、B两组患者症状评分差别无统计学意义；24h食管pH监测A组患者较B组患者存在较多的病理性酸反流；而A、B两组患者食管鳞状上皮细胞间隙增宽程度接近。结论胃食管反流患者均存在不同程度细胞间隙增宽，细胞间隙增宽可能导致NERD患者对生理性酸反流的高敏感性。     

非糜烂性胃食管反流病患者酸灌注及食管扩张脑诱发电位的研究

目的研究非糜烂性胃食管反流病(NERD)患者和正常人食管扩张刺激(OD)-脑诱发电位(CEP)的特征及食管酸灌注后 CEP 的改变,探讨 NERD 患者食管内脏高敏感性的发生机制。方法10例健康志愿者和21例 NERD 患者参与试验;采用 Synectics 内脏刺激器/电子气压泵和带有低顺应性气囊及多个灌注式压力通道的导管给食管以时相性扩张刺激和酸灌注;利用食管气囊扩张术检测受试者食管最大耐受痛阈,用75%最大疼痛耐受容积作为诱发刺激的强度(刺激频率为12次/min,连续64次);采用 OD-CEP 系列技术记录并分析食管酸灌注前后 NERD 患者和正常人 CEP 的变化。组间比较采用 t 检验,多组间比较采用单因素方差分析。结果食管时相性机械扩张刺激诱发出可识别、可重复、多峰的 CEP 波形,以 NP 型为主。正常对照者 N1、P1、N2波潜伏期分别为(246±77)、(388±84)和(502±78)ms,NERD 患者 CEP 波形变异性大,其 N1、P1、N2波潜伏期分别为(192±46)、(293±76)和(440±79)ms,较对照组明显缩短(P 值均<0.05);P1-N2峰间波幅明显增加[(6.2±1.9)μV 比(7.8±3.2)μV,P<0.05]。食管酸灌注能明显缩短 NERD 患者 N1、P1、N2波潜伏期,与酸灌注前相比差异有统计学意义(P 值均<0.05),且酸灌注后 NERD 患者 P1-N2皮层波幅值较酸灌注前显著增加(p<0.05),健康对照组除 CEP 的 N1波潜伏期较对应基线值显著降低(P=0.05)外,其余 CEP 参数均无明显改变。结论 NERD 患者存在食管对机械和酸刺激的高敏感性及食管-中枢内脏感觉传导通路失凋。     

The immunoneuroendocrine role of melatonin

Abstract: A tight, physiological link between the pineal gland and the immune system is emerging from a series of experimental studies. This link might reflect the evolutionary connection between self-recognition and reproduction. Pinealectomy or other experimental methods which inhibit melatonin synthesis and secretion induce a state of immunodepression which is counteracted by melatonin. In general, melatonin seems to have an immunoenhancing effect that is particularly apparent in immunodepressive states. The negative effect of acute stress or immunosuppressive pharmacological treatments on various immune parameters are counteracted by melatonin. It seems important to note that one of the main targets of melatonin is the thymus, i.e., the central organ of the immune system. The clinical use of melatonin as an immunotherapeutic agent seems promising in primary and secondary immunodeficiencies as well as in cancer immunotherapy. The immunoenhancing action of melatonin seems to be mediated by T-helper cell-derived opioid peptides as well as by lymphokines and, perhaps, by pituitary hormones. Melatonin-induced-immuno-opioids (MHO) and lymphokines imply the presence of specific binding sites or melatonin receptors on cells of the immune system. On the other hand, lymphokines such as -γ-interferon and interleukin-2 as well as thymic hormones can modulate the synthesis of melatonin in the pineal gland. The pineal gland might thus be viewed as the crux of a sophisticated immunoneuroendocrine network which functions as an unconscious, diffuse sensory organ.     

Response of rat pineal melatonin to calcium, magnesium, and lithium is circadian stage dependent

Abstract: Herein we documented the response of pineal melatonin production to electrolytes known to be effective on pineal function in view of a possible circadian stage dependence. We studied the release of melatonin by perifused rat pineal glands at 2 different circadian stages corresponding to the middle of the light and dark periods, i.e., respectively, 7 and 19 HALO (Hours After Light Onset, L:D = 12:12). The initial efflux rates were, as expected, much higher in the perifusates of glands removed from rats sacrificed during the dark phase than of those removed during the light phase. After 3 hr of perifusion, melatonin release reached similar levels which were found constant up to the 8th hr of perifusion, whatever the circadian stage. Perifusion of the glands with physiological concentrations for the rat of calcium (5.2 mmol/1) and magnesium (1.34 mmol/1) resulted in a stimulatory effect on the pineal glands removed from rats sacrificed in the middle of the dark period (19 HALO), whereas no effects were observed on the pineal glands removed from rats sacrificed during the light (7 HALO). Lithium (0.28 and 0.55 mmol/1) was ineffective on melatonin release in pineal glands removed 7 and 19 HALO. Our results show differences in the initial efflux rates of melatonin and in the response of perifused pineal glands to calcium and magnesium according to the circadian stage.     

Changes in connexin43, the gap junction protein of astrocytes, during development of the rat pineal gland

Abstract: The abundance of gap junctions between rat pineal astrocytes formed by connexin43 (Cx43) was studied during development. Levels and distribution of Cx43 were measured by immunoblotting and indirect immunofluorescence, respectively. The amount of Cx43 in cells located within the gland was low until about the 7th postnatal day and increased to adult values between the 14th and 21st days postpartum. Although astrocytes, recognized by their vimentin immunoreactivity, were scarce before birth, they were abundant by the 7th postnatal day suggesting that the low levels of Cx43 found at this age corresponded to a low expression of this protein. Localization of the immunoreactivity to Cx43 and vimentin showed a close correlation, indicating that mature or immature pineal astrocytes form gap junctions made of Cx43. Since Cx43 levels attained their adult values at about the time the innervation and the functional state of the gland reached maturity (2–3 weeks after birth), it is proposed that astrocyte gap junctions are involved in the function of the adult rat pineal gland.     

Conservative management of perforated duodenal diverticulum： A case report and review of the literature

Duodenal diverticula are a relatively common condition. They are asymptomatic, unless they become complicated, with perforation being the rarest but most severe complication. Surgical treatment is the most frequently performed approach. We report the case of a patient with a perforated duodenal diverticulum, which was diagnosed early and treated conservatively with antibiotics and percutaneous drainage of secondary retroperitoneal abscesses. We suggest this method could be an acceptable option for the management of similar cases, provided that the patient is in good general condition and without septic signs.     

Presence of immunoreactive growth hormone and prolactin in the ovine pineal gland

Abstract: The use of antisera raised against bovine growth hormone (GH) and ovine prolactin (PRL) enabled the detection of related immunoreactive (ir) sequences of proteins in ovine pineal tissue. The isolation of PRL-like ir-material was accomplished using a 0.25 M ammonium sulphate (pH 5.5) extraction followed by ethanol precipitation, whereas the resulting 2.0 M ammonium sulphate (pH 7.0) precipitate contained a GH-like immunoreactivity. Gel chromatography of the GH-like immunoreactivity (Sephadex G-100) indicated the presence of several GH-like fragments ranging in the M_r range of 7,000 to 55,000. Analyses of the PRL-like ir-material found in pineal tissue on HPLC using a TSK 545-DEAE column led to the resolution into a single peak of immunoreactivity. A single peak of activity was also observed following chromatofocusing and hydrophobic interaction chromatography of the ir-peak from the TSK 545-DEAE column. The PRL-like ir-material inhibited the binding of [¹²⁵I]ovine PRL-S14 to anti-ovine PRL antibodies without showing an affinity for binding to anti-rat PRL or anti-bovine GH antibodies. Scatchard analysis of the binding of pineal PRL-like ir-material and pituitary ovine PRL-S14 to liver membranes from day-20 pregnant rats revealed similar affinity constants (K_a of 4.7 ± 0.2 × 10⁹ M^-1). In addition, the replication of Nb 2 Node rat lymphoma cells was stimulated by pineal PRL-like ir-material, an effect known to be specific for lactogenic hormones. The pineal PRL-like immunoreactivity appeared on sodium dodecyl sulfate polyacrylamide gels as a single major band of M_r 24,000. The functional status of PRL-and GH-like ir-material in the ovine pineal remains to be determined, but evidence is presented that the overall protein synthesis rate of the rat pineal responded to circulating concentrations of PRL.     

Microbiology of human immunodeficiency virus anorectal disease

PURPOSE: Individuals who are seropositive for the human immunodeficiency virus are at high risk for opportunistic infection and anorectal disorders. Little prospective information is available regarding anorectal pathogens in these patients. METHODS: One hundred sixty-three HIV-seropositive patients presented to the colorectal clinic between 1989 and 1992. Forty-seven (29 percent) patients were thought to have an infectious process and were prospectively studied using a standardized multiculture protocol. RESULTS: Mean age was 33 (range, 19–59) years. All were male; high-risk behavior accounted for 87 percent of HIV transmissions. Presenting complaints included anorectal pain (79 percent), pus per anum (28 percent), and blood per anum (26 percent). Examination revealed perianal tenderness (60 percent), condyloma (38 percent), perianal ulcers (38 percent), and anal fissures (34 percent). Sixty-six sets of cultures were performed; 28 patients had one set, 15 had two sets, and 4 had three sets. Thirty-two of these 47 patients (68 percent) had positive cultures including herpes (50 percent), cytomegalovirus (25 percent),Neisseria gonorrhoeae (16 percent), chlamydia (16 percent), acidfast bacilli (2 percent), and others (9 percent). Six of 32 patients with positive cultures had more than one organism cultured. Sixteen (50 percent) patients with positive cultures were treated medically, 8 (25 percent) were treated surgically and 8 (25 percent) were treated with both modalities. Sixty-one procedures were performed on 17 patients for condylomata. Eighteen patients had 20 procedures for abscesses, 50 percent of whom had positive cultures for other than common bowel flora; all improved. Fourteen patients underwent 33 procedures for perianal fistulas.Mycobacterium fortuitum was cultured from one patient who required 13 procedures for abscesses and fistulas. Forty-five (96 percent) patients were followed for an average of 12.5 months ±2.9 SEM (range, 1–94 months). Symptoms were improved or resolved in 22 of 32 (69 percent) patients with positive cultures and in 11 of 13 (84 percent) with negative cultures. CONCLUSIONS: Specific pathogens may often be identified in human immunodeficiency virus-seropositive patients with anorectal disorders if aggressively sought. Although patients without specific pathogens identified may be expected to improve with planned empiric treatment, positive identification allows more directed therapy.