世界胃肠病学会全球指南:非酒精性脂肪性肝病及非酒精性脂肪性肝炎

<正>1介绍过去数十年中,非酒精性脂肪性肝病(nonalcoholic fatty liver disease,NAFLD)及非酒精性脂肪性肝炎(nonalcoholic steatohepatitis,NASH)是西方国家肝病的首要原因。在过去20年其他慢性肝病发病率保持稳定甚至下降的情况下,NAFLD的发病率却呈现翻番。最近的数据证明,NAFLD及NASH在中东、远东、非洲、加勒     

非酒精性脂肪性肝炎的临床试验设计和治疗终点

非酒精性脂肪性肝病（nonalcoholic fatty liver disease。NAFLD）是慢性肝病的常见病因．非酒精性脂肪性肝炎（nonalcoholic steatohepatitis,NASH）是NAFLD的进展形式,与肝病相关病死率和心血管疾病风险增加相关。当前,肝活检是惟一被临床广泛接受的诊断方法．可评估NASH向肝硬化进展．对NASH患者尚无确证的非创伤性诊断方法和公认的治疗措施。     

非酒精性脂肪性肝病药物研发终点必须为临床获益

<正>非酒精性脂肪性肝病(nonalcoholic fatty liver disease,NAFLD)的疾病谱包括非酒精性单纯性脂肪肝(nonalcoholic fatty liver,NAFL)、非酒精性脂肪性肝炎(nonalcoholic steatohepatitis,NASH)及其相关肝硬化。随着肥胖症、糖尿病和代谢综合征全球化流行趋势,NAFLD现已成为包括我国在内的世界诸多国家和地区慢性肝脏疾病的首要病因。NAFLD不仅增加肝脏疾病残疾和死亡而且增加心血管事件相关死亡     

非酒精性脂肪性肝病与肝移植

随着生活水平的提高,非酒精性脂肪性肝病(nonalcoholic fatty liver disease,NAFLD)在人群中的发病率越来越高.非酒精性脂肪性肝炎(nonalcoholic steatohepatitis,NASH)是NAFLD的最严重类型,在发达国家已成为临床上最常见的慢性肝病类型.     

非酒精性脂肪性肝病诊疗指南

非酒精性脂肪性肝病(nonalcoholic fatty liver disease,NAFLD)是一种与胰岛素抵抗(insulin resistance,IR)和遗传易感密切相关的代谢应激性肝脏损伤,其病理学改变与酒精性肝病(alcoholic liver disease,ALD)相似,但患者无过量饮酒史,疾病谱包括非酒精性单纯性脂肪肝(nonalcoholic simple fatty liver,NAFL)、非酒精性脂肪性肝炎(nonalcoholic steatohepatitis,NASH)及其相关肝硬化和肝细胞癌[1-2].     

蛋白质组学技术在非酒精性脂肪肝研究中的应用

非酒精性脂肪肝（nonalcoholic fatty liver，NAFL），又称非酒精性脂肪性肝病（nonalcoholic fatty liver disease，NAFLD），是一组以肝细胞脂肪变性、坏死、炎性细胞浸润等为主要特征的临床病理综合征，其肝脏组织学病变与酒精性肝病相类似，但无过量饮酒史。根据病理学改变及临床表现，可将NAFLD分为单纯性NAFLD和非酒精性脂肪性肝炎（nonalcoholic steatohepatitis，NASH）。NASH却可逐渐进展为肝硬化、肝癌等终末期肝病，已成为目前仅次于慢性病毒性肝炎和酒精性肝病的重要肝硬化前期病变。     

非酒精性脂肪肝的西医治疗进展

<正>非酒精性脂肪性肝病(nonalcoholic fatty liver disease,NAFLD)是一种与胰岛素抵抗,糖尿病、肥胖等代谢危险因素密切相关的应激性肝脏损伤,其疾病谱包括非酒精性单纯性脂肪肝(nonalcoholic simple fatty liver,NAFL)、非酒精性脂肪性肝炎(nonalcoholic steatohepatitis,NASH)及其相关肝硬化和     

受控衰减参数在脂肪肝诊断中的应用

<正>脂肪性肝病(fatty liver disease,FLD)是以弥漫性肝细胞大泡性脂肪变为主要特征的临床病理综合征,主要包括酒精性肝病(alcoholic liver disease,ALD)和非酒精性脂肪性肝病(nonalcoholic fatty liver disease,NAFLD),疾病谱包括单纯性脂肪肝、脂肪性肝炎及其相关肝硬化[1]。随着肥胖、糖尿病和酒精滥用成为全球化的流行趋势,无论是NAFLD还是ALD都已成为重要的公共健康问题,并且酒精性和非酒精性FLD     

CK18诊断非酒精性脂肪性肝病的价值

非酒精性脂肪性肝病（nonalcoholic fatty liver disease,NAFLD）包括单纯性非酒精性脂肪肝（nonalcoholic fatty liver,NAFL）、非酒精性脂肪性肝炎（nonalcoholic steatohepatitis,NASH）,前者是良性非进展性的,而后者可进展为肝硬化、肝衰竭甚至肝细胞癌。因此,区分NASH和NAFL的意义重大。细胞角蛋白18（cytokeratin18,CK18）是肝脏内主要的中间丝蛋白,多项研究表明,外周血中经凋亡蛋白酶分解后的CK18片段的含量与肝细胞的凋亡水平相关;而在慢性肝病中,凋亡是肝细胞死亡的主要方式,血清中CK18片段水平升高可见于NAFLD、病毒性肝炎、酒精性肝病、药物性肝炎、胆汁淤积性肝病、肝细胞癌等,提示CK18片段可作为无创诊断慢性肝病的生物标志物。本文综述近年关于CK18及其分解片段的临床研究,并对其在NAFLD诊断中的价值加以评价。     

Nrf2在非酒精性脂肪性肝病中的调节作用

正非酒精性脂肪性肝病(nonalcoholic fatty liver disease,NAFLD)是一种普遍存在的疾病,目前被认为是西方最常见的肝病~([1]),近年来在我国的发病率也愈来愈高~([2])。NAFLD是指在没有过量饮酒的情况下,肝脏中过多脂肪的积累。虽然其最初是良性的,但是会从单纯的非酒精性脂肪变性逐渐发展为非酒精性脂肪性肝炎(nonalcoholic steatohepatitis,NASH),随后     

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.