常占杰教授从痰瘀互结论治非酒精性脂肪性肝病的学术经验

非酒精性脂肪性肝病(NAFLD)是一种以肝脏中过量脂肪堆积、脂肪变性为病理学特征的肝脏疾病,包括单纯性非酒精性脂肪肝、非酒精性脂肪性肝炎(NASH)以及相关的肝硬化和肝癌[1]。目前我国NAFLD发病率居高不下并且逐年上升,已造成严重的社会负担和医疗压力。现代医学在NAFLD发病机制方面研究进展较快,但治疗药物和干预手段方面进展缓慢,而传统中医药治疗肝脏疾病历史悠久,对NAFLD的治疗也具有明显特点。吾师常占杰教授为陕西省名中医,从事中医药防治肝胆疾病的30余年,形成了自己独特的见解和诊疗思路。本文主要介绍常占杰教授从痰瘀互结论治NAFLD的学术经验,以飨同道。     

非酒精性脂肪性肝病的同质性和异质性

非酒精性脂肪性肝病(NAFLD)已经成为世界和我国流行最高的肝脏疾病。NAFLD在发病机制、病理学、临床表型等方面具有异质性。在发病机制方面,至少包括代谢/肥胖因素和基因多态性的因素;在病理学方面,成人NAFLD的肝纤维化表现为非典型的纤维化和窦纤维化,而儿童的NAFLD患者的肝纤维化在早期主要表现为汇管区纤维化,部分表现为小叶纤维化;在临床表型方面,NAFLD又可以表现为伴或不伴有糖尿病、伴或不伴有肥胖。这些异质性提示临床诊断、治疗和治疗效果评价的策略与方法不同。     

非酒精性脂肪性肝病治疗方法的评估

非酒精性脂肪性肝病(NAFLD)是遗传环境一代谢应激相关性肝脏疾病，病理上包括单纯性脂肪肝(nonalcoholicfatty liver,NAFL)及由其演变的脂肪性肝炎(NASH)和脂肪性肝硬化等类型。NAFLD治疗方法很多，但其临床疗效的评估标准尚在探讨过程中。目前，一般认为NAFLD的治疗重点在于去除病因，治疗原发疾病；调整饮食，纠正不良生活习惯，合理运动以及辅以一定的药物治疗。     

肝穿刺活组织检查及病理学诊断中的相关技术及应用

肝脏病理学检查在指导临床治疗和评估疾病预后方面具有重要的地位和作用,特别是对疑难肝脏疾病的确诊至关重要。通过开展肝穿刺活组织检查,选用合理的病理学技术方法,有助于病理医生观察肝脏组织的形态学改变,为疾病的诊断、鉴别诊断以及明确病因提供重要参考。介绍了肝活组织病理学诊断的常用技术,以提高临床医师对肝脏病理学改变的认识水平,加强临床与病理联系,为肝脏疾病、特别是疑难肝病的确诊提供有力的帮助。     

非酒精性脂肪性肝病治疗的研究进展

非酒精性脂肪性肝病（non-alcoholic fatty liver disease, NAFLD）是以肝脏脂肪堆积和炎症为表现的代谢性疾病，可进展为肝硬化和肝癌等。随着人们生活方式的转变，NAFLD的发病率越来越高。近期研究增强了对其流行病学、诊断和治疗的认识。目前对NAFLD的治疗主要使用非药物干预手段，如运动、饮食控制和减肥手术等，但仍缺乏特效治疗药物，一些药物正在研发，但尚未获批。本文就NAFLD治疗的研究进展进行综述。     

酸性鞘磷脂酶在非酒精性脂肪性肝病中的作用及应用前景

酸性鞘磷脂酶(ASMase)与多种肝脏疾病的发病机制相关。近年来研究发现,ASMase在非酒精性脂肪性肝病(NAFLD)患者及动物肝脏中表达增加,且可导致氧化应激、脂质沉积、脂毒性、炎性反应、纤维化等改变。此文综述了ASMase在NAFLD发病机制中的作用,并评价其在NAFLD的预测、诊断、靶向治疗以及预后判断方面的潜在应用价值。     

非酒精性脂肪性肝病的药物治疗研究进展

非酒精性脂肪性肝病(NAFLD)是常见的肝脏疾病,目前NAFLD的治疗仍主要依靠对患者生活方式的调整,至今药物治疗的效果不理想。随着近年来学者们对其发病机制的深入研究,NAFLD药物治疗方面取得了重大研究进展。由于患者对药物治疗的依从性较好,因此对药物在临床应用中的筛选将为NAFLD的治疗提供新的选择。该文结合近年来国内外学者对NAFLD的研究进展及临床治疗经验,综述一些有望用于NAFLD治疗的药物,包括药物作用的理论依据、作用机制、研究进展等。     

非酒精性脂肪性肝病药物研发失败的原因

1980年,美国梅奥诊断Ludwig等将无过量饮酒史患者的脂肪性肝病定义为非酒精性脂肪性肝病(NAFLD)。尽管学术界对此存有争议,但是至今国际上仍在沿用当初的疾病命名和诊断标准。随着肥胖在全球的流行,NAFLD现已累及全球四分之一的人口并且起病渐趋低龄化。NAFLD与肝硬化、糖尿病、心血管疾病以及多种恶性肿瘤的高发密切相关,给个人和家庭以及医疗卫生系统造成巨大的疾病负担。当前英国、法国、德国和意大利等欧洲四国由NAFLD直接导致的年医疗费用高达350亿欧元,而美国则可能超过1000亿美元。至今仍缺乏治疗NAFLD的有效药物,大多数治疗药物的2b期和3期临床试验未达到或仅勉强达到要求的肝脏组织学终点,主要原因包括当前对NAFLD的异质性缺乏理性认识,以及所研发的新药的治疗靶点仍不够精确。     

非酒精性脂肪性肝病在研新药的进展

非酒精性脂肪性肝病(NAFLD)是全世界最常见的肝脏疾病,与肥胖、胰岛素抵抗和其他代谢性疾病密切相关。目前尚无批准用于治疗的药物,常规的生活方式管理也难以对疾病产生积极的影响。对目前在研的代谢调节剂、抗炎抗氧化剂及抗纤维化剂等NAFLD治疗药物进行了综述,归纳总结了其临床研究结果,为NAFLD的临床治疗及药物研发提供新思路。     

我国非酒精性脂肪性肝病的研究现状

随着非酒精性脂肪性肝病(NAFLD)患病率的不断增加,公众的重视程度得到提高,相关研究逐渐增多,也取得了一些重要的进展。介绍了近5年来,我国在NAFLD的流行病学、危险因素、发病机制、无创性诊断、治疗及相关肝硬化和肝癌等方面重要的研究成果,了解我国的研究现状。指出与国际相比,我国相关临床和基础研究还存在一定的差距,尤其在公众的认知及医务工作者的重视度等方面;未来还应加强在流行病学、发病机制、患者的管理及药物治疗等方面的研究。     

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.