近15年我国炎症性肠病文献分析

背景：过去认为我国炎症性肠病（IBD）较少见，但研究显示近年我国IBD患者和相关文献逐渐增多。目的：了解我国IBD病例数和研究现状，为今后IBD的研究和诊治提供借鉴。方法：通过中国生物医学文献数据库（CBMDisc）和维普中文科技期刊全文数据库（VIP）检索1989年1月-2003年12月有关IBD文献，逐篇查阅全文并分析IBD病例数和研究现状。结果：共3384篇IBD文献入选，其中基础性文献12．8％，诊断性文献6．3％，治疗性文献61．6％，综述15．8％，其他3．5％。共报道了143511例IBD患者，其中溃疡性结肠炎（UC）患者140114例，克罗恩病（CD）患者3397例。UC和CD病例数均呈上升趋势。UC临床症状以腹泻最为常见（83．2％），CD以腹痛最为常见（86．6％）。UC的发病部位以全结肠最为常见（42．0％），CD以小肠型最为常见（40．2％）。UC的发病类型以慢性复发型最为常见（57．6％）。仅40．6％的诊断性文献使用了诊断标准。UC和CD的漏诊率分别为32．1％和60．9％。在2084篇IBD治疗性文献中，1533篇（73．6％）为临床药物治疗性文献，仅598篇（28．7％）文献可根据循证医学标准分类。在1533篇临床药物治疗性文献中，1376篇（89．8％）为中医治疗和中西医结合治疗文献；仅675篇（44．0％）为对照试验，12篇（0．8％）为随机对照试验。结论：近15年我国IBD相关文献及其报道的病例数不断增多，但IBD的基础研究比例较低，临床诊断和药物试验设计欠规范，论证强度不高。     

炎症性肠病合并神经内分泌肿瘤的临床特征分析

报道1例炎症性肠病（inflammatory bowel disease,IBD）合并神经内分泌肿瘤（neuroendocrine neoplasms,NENs）病例,结合文献报道的69例病例,总结分析IBD合并NENs的临床特征,探索两者之间的关系。69例IBD合并NENs患者中包括32例克罗恩病（Crohn disease,CD）及37例溃疡性结肠炎（ulcerative colitis,UC）,男女发病率相当（P=0.151）。NENs多形成于IBD之后。CD患者发生NENs的中位病程为4.5年,小于UC患者的17年（P=0.002）。33例患者为术后或随访时发现NENs,有症状者中11例表现为肠梗阻。NENs好发部位与IBD相似,CD患者好发于回肠和阑尾（27例）,而UC患者好发于结直肠（31例）（P<0.001）。CD患者中神经内分泌瘤更常见（26例）,神经内分泌癌则在UC患者中更普遍（22例）（P<0.001）。IBD可合并或并发NENs,临床表现无特异性,病因尚不明确,有待进一步探索。     

HMGCS2、PPARγ在炎症性肠病患者肠黏膜的表达活性及临床意义

目的观察HMGCS2、PPARγ在溃疡性结肠炎（uc）及克隆恩病（CD）中的表达情况,通过对UC、CD及健康对照组比较,分析其在IBD发生发展的分子学基础。方法收集南方医院消化科病房及门诊2010年2月-2011年1月间所行常规全结肠镜检查后内镜下活检的73例UC、42例CD、89例健康对照者的肠黏膜。比较UC组和CD组之间一般临床特点和检查资料的差异。结果73例UC中发生在直肠的28例（38．4％）,发生在直乙状结肠9例（12．3％）,发生在左半结肠的11例（15．1％）,发生在全结肠的25例（34．2％）;42例CD患者有29例发生在回末和小肠（69．0％）。HMGCS2、PPARγ在73例UC患者肠黏膜中阳性表达分别为48例（65．8％）和36例（49．3％）;在42例CD患者肠黏膜中阳性表达分别为37例（88．1％）和30例（71．4％）;在89例正常对照组肠黏膜阳性表达占82例（92．1％）和66例（74．2％）。结论HMGCS2、PPARγ在UC、CD、健康对照组均有表达,在UC患者肠黏膜明显下调,而在CD和健康者无明显变化。     

炎症性肠病患者肠黏膜组织中miR-129与PDCD4表达的关系及意义

目的 探究炎症性肠病（IBD）患者肠黏膜组织中miR-129与程序性细胞死亡因子4(PDCD4)的表达关系及临床意义。方法 选择2017年7月至2020年1月万宁市人民医院收治的176例活动期IBD患者设为IBD组,其中94例为溃疡性结肠炎（UC）患者（设为UC组）,82例为克罗恩病（CD）患者（设为CD组）;另选择同期在该院就诊的100例结肠息肉患者设为对照组。在IBD组患者行肠镜检查时取肠黏膜病变组织,在对照组患者行肠镜下息肉切除术时取距息肉>5 cm的回肠或结肠黏膜活体组织。采用实时荧光定量PCR法检测肠黏膜组织中miR-129和PDCD4的表达水平,并分析两者的相关性,以及其与患者疾病活动度的关系。采用ROC曲线评估肠黏膜组织中mi R-129和PDCD4诊断IBD的效能。结果 IBD组肠黏膜组织中miR-129、PDCD4的相对表达量分别为0.82±0.23、0.67±0.19,均低于对照组（1.36±0.35、1.02±0.27）,2组的差异均有统计学意义（P均<0.05）。轻度UC组、中度UC组、重度UC组的miR-129和PDCD4表达水平依次降低,轻度CD...     

核周型抗中性粒细胞胞质抗体和抗酿酒酵母抗体在炎症性肠病中的临床意义

核周型抗中性粒细胞胞质抗体（pANCA）和抗酿酒酵母抗体（ASCA）是一组与炎症性肠病（IBD）密切相关的免疫球蛋白,但对溃疡性结肠炎（UC）、克罗恩病（CD）的诊断和鉴别诊断的价值仍有待进一步验证。目的：探讨pANCA和ASCA在UC与CD诊断和鉴别诊断中的意义。方法：以酶联免疫吸附测定（ELISA）检测64例UC、62例CD和56例健康对照者的血清pANCA、ASCA水平和阳性率,分析pANCA、ASCA及其组合的诊断敏感性、特异性、阳性预测值（PPV）和阴性预测值（NPV）。结果：UC组血清pANCA水平[（584．22±347．70）pg/ml对（304．99±211．10）pg／ml和（390．92±82．82）pg/ml,P〈0．01]和阳性率（50．0％对14．5％和14.3％,P〈0．01）显著高于CD组和健康对照组,三组间血清ASCA水平和阳性率无明显差异。pANCA^＋和pANCA^＋/ASCA-诊断UC的敏感性、特异性、PPV和NPV分别为50．0％、85．7％、80．0％、60．0％和42．2％、89.3％、81．8％、57．5％,ASCA^＋和ASCA^＋／pANCA^-诊断CD的敏感性、特异性、PPV和NPV分别为8．1％、87．5％、41．7％、46.2％和3.2％、91．1％、28．6％、45．9％。结论：pANCA阳性有利于UC的诊断。pANCA／ASCA联合检测有助于鉴别UC,但对CD诊断价值不高。     

骨桥蛋白在炎症性肠病患者结肠组织中的表达

背景：骨桥蛋白（OPN）是一种分泌型磷酸化糖蛋白,参与细胞信号转导,促进细胞黏附和迁移。近年研究发现炎症性肠病（IBD）患者血浆OPN水平升高,患者结肠黏膜中可检出OPN表达。目的：了解OPN在IBD患者结肠黏膜组织中的表达情况,探讨其在IBD发病机制中的作用。方法：以免疫组化半定量方法检测53例溃疡性结肠炎（UC）、62例克罗恩病（CD）和15例源自结肠腺瘤患者的正常结肠组织标本中OPN的表达。结果：OPN广泛表达于结肠黏膜上皮细胞和固有层渗出细胞。UC组和CD组结肠上皮细胞的OPN平均光密度值显著低于对照组（11．84±0．98和10．04±1．37对12．64±1．45,P〈0．05）,结肠黏膜固有层渗出细胞的OPN阳性细胞百分率则显著高于对照组（20．31％±4．50％和12．69％±3．06％对3．85％±0．66％,P〈0．001）。UC和CD患者的病情严重程度与结肠上皮细胞和固有层渗出细胞中的OPN表达量均无相关性。结论：OPN在IBD患者结肠黏膜上皮和同有层中的表达不一致,结肠上皮细胞中OPN表达下调可能与肠黏膜屏障功能受损有关,而黏膜固有层渗出细胞中OPN表达上调可能与免疫反应有关。     

炎症性肠病858例临床分析

目的总结分析炎症性肠病（IBD）的临床特点,探讨诊治策略。方法对1998年1月至2009年7月354例炎症性肠病住院患者和2003年1月至2009年7月504例炎症性肠病门诊患者资料进行回顾性分析。结果本组资料显示我院近12年来IBD发病呈逐年上升趋势,溃疡性结肠炎（UC）明显多于克罗恩病（CD）。本组IBD患者中男女之比为1.28∶1。IBD平均发病年龄（41.07±16.07）岁。UC发病高峰年龄为30～49岁,CD发病高峰年龄为20～39岁。本组住院患者中UC和CD两组民族构成比较无统计学差异。肠镜检查中UC以直肠和乙状结肠病变为主,CD以回盲部及回肠末端病变为主。本组患者IBD病理组织学检出率为41.5%,UC误诊率为17.0%,CD误诊率为25.0%。治疗以氨基水杨酸类及类固醇激素为主。结论炎症性肠发病数呈逐年上升趋势;IBD诊断主要依靠内镜及病理。IBD呈慢性复发性发作过程,应长期维持治疗。     

单核样髓源性抑制细胞在炎症性肠病中的表达及其临床意义

背景：近年来炎症性肠病（IBD）发病率呈上升趋势,其病理生理学机制复杂且仍未明确。目的：研究单核样髓源性抑制细胞（MDSCs）在IBD患者外周血单核细胞中的比例,分析单核样MDSCs与IBD活动性的关系,从而初步探讨单核样MDSCs在IBD中的作用机制。方法：纳入IBD患者60例,分为克罗恩病（CD）组（n=33）和溃疡性结肠炎（UC）组（n=27）,选取30名同期健康体检者作为正常对照组,采用流式细胞仪检测CD组、UC组、正常对照组患者外周血单核样MDSCs／单核细胞比例,分析单核样MDSCs与IBD患者WBC、PLT、ESR、CRP的相关性。结果：CD组和UC组外周血单核样MDSCs／单核细胞比例较正常对照组相比显著升高[（43．7±23．0）％、（49．1±27．2）％对（10．7±7．4）％]（P〈0．01）,CD组与UC组相比差异无统计学意义（P〉0．05）。活动期CD和UC组外周血单核样MDSCs／单核细胞比例均较缓解期组显著升高[（60．3±16．8）％、（66．3±17．6）％对（28．1±16．2）％、（19．9±9．0）％]（P〈0．01）。IBD患者外周血单核样MDSCs／单核细胞比例与WBC计数、PLT计数呈正相关（r=0．44,P=0．02;r=0．43,P=0．02）,与ESR、CRP不相关（r=0．33,P=0．08;r=0．30,P=0．12）。结论：IBD患者外周血单核样MDSCs比例明显升高,与IBD活动性密切相关。单核样MDSCs在IBD发病中具有重要作用。     

炎症性肠病患者血清纤维化指标的变化

背景：炎症性肠病（IBD）具有慢性和反复发作的特点，肠壁组织反复损伤和修复可致局部纤维化和瘢痕形成。目的：观察IBD患者常用血清纤维化指标层黏蛋白（LN）、Ⅳ型胶原（C-Ⅳ）、透明质酸（HA）和Ⅲ型前胶原氨基端肽（PmNP）的变化，评价其与疾病活动度的关系。方法：收集经结肠镜和活检病理检查确诊的48例溃疡性结肠炎（UC）患者、50例克罗恩病（CD）患者和50例对照者，以放射免疫测定检测血清LN、C-1V、HA和PmNP水平，以酶联免疫吸附测定（ELISA）检测血清高敏C反应蛋白（hs-CRP）水平。结果：与对照组相比，UC和CD患者血清LN水平显著增高，C-Ⅳ和PⅢNP水平显著降低（P〈0．05），UC和CD两组间则无明显差异；三组间血清HA水平均无明显差异。血清hs-CRP水平可反映IBD疾病活动度，活动期患者hs-CRP水平均高于200mg／L。IBD患者的LN水平与hs-CRP呈正相关（UC：r=0．33，CD：r=0．53，P〈0．05），C-Ⅳ和PmNP水平与hs-CRP无明显关联。LN水平与CD病变部位无明显关联。结论：IBD患者血清LN水平增高，C-Ⅳ和PmNP水平降低．可能成为肠壁组织炎症和修复的间接标志物：血清LN水平可间接反映IBD疾病活动度。     

合并肠外表现的炎症性肠病患者英夫利西单抗治疗效果分析

背景：炎症性肠病（IBD）发病率呈逐年升高的趋势,部分IBD患者合并肠外表现（EIM）,且EIM对IBD治疗产生一定的影响。目的：总结合并EIM的IBD患者临床特征,并评价英夫利西单抗（IFX）的治疗效果。方法：回顾性分析2010年1月—2020年12月于大连医科大学附属第一医院诊断为IBD且同时合并EIM患者的临床资料,探讨IFX的治疗效果。结果：811例IBD患者中,50例（6.17%）合并EIM。EIM以关节炎（78.00%）、结节性红斑（26.00%）最为常见。52.00%的IBD患者合并1种EIM。合并EIM的UC患者中病变范围累及以E3最常见（68.42%）,CD患者以L3最常见（50.00%）。共21例患者接受IFX治疗,用药后第2周HB、ALB明显上升,ESR、CRP、PLT明显下降;第22周83.33%的UC患者转为轻度,70.00%的CD患者进入缓解期。应用IFX后关节炎首次消失时间明显短于未应用IFX组（2.50 d对10.50 d,P<0.05）。CRP升高者关节炎首次消失中位时间亦明显短于CRP正常者（3.00 d对9.00 d,P<0.05）。结...     

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.     

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.     

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.     

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.