乙型肝炎病毒和丙型肝炎病毒相关性肝癌的研究进展

乙型肝炎病毒(HBV)和丙型肝炎病毒(HCV)相关的原发性肝细胞癌(HCC)发生机制复杂,其可通过介导机体免疫功能紊乱诱导慢性炎症和产生炎性因子,调控多种癌症信号通路诱导HCC的发生和进展.HBV可通过病毒基因整合、病毒蛋白(主要是HBx、PreS)变异诱导宿主基因不稳定发生插入、缺失等突变诱导HCC的发生和进展.HC...     

免疫检查点对慢性HBV感染者自然杀伤细胞功能的影响

慢性HBV感染的机制尚未完全阐明，HBV可诱发宿主免疫细胞功能障碍，引起免疫失衡和功能缺陷，这可能是HBV感染慢性化的机制之一。在慢性HBV感染中，自然杀伤(NK)细胞的功能是衰竭的，可能与其细胞表面免疫检查点分子的表达上调相关，阻断免疫检查点可以恢复NK细胞的功能。本文将从HBV病原学、慢性HBV感染机制以及常见免疫检查点在慢性乙型肝炎中对NK细胞功能的影响等方面进行系统综述，旨在为慢性HBV感染的治疗提供新的思路。     

从慢性乙型肝炎免疫和病原学特点探讨临床治疗策略

HBV严重威胁人类健康。目前全球约有4亿慢性HBV携带者，每年约有100万人死于HBV感染相关性肝脏疾病。HBV是嗜肝的非细胞毒性DNA病毒，无细胞毒效应，其导致肝损害的机制是免疫介导，即机体免疫系统活化产生病毒特异性细胞毒T细胞，并释放细胞因子等，在清除病毒感染肝细胞的同时导致局部炎性反应，损伤肝细胞。HBV感染的自然过程和结局与感染者的年龄、病毒载量以及机体的免疫状态等有关，而机体抗病毒的免疫应答是决定疾病转归以及治疗效果的关键因素。     

乙型肝炎病毒反转录酶mRNA表达与乙型肝炎病毒相关肝细胞癌的关系

HBV持续感染不仅能引起慢性乙型肝炎(乙肝),最终还可导致肝硬化、肝细胞癌(HCC).近年来发现,肝外细胞,尤其是外周血单个核细胞(PBMC)中,HBV的存在和复制是导致机体HBV长期感染的重要原因[1-2].目前,虽然针对HBV的研究已经非常深入,但HBV相关HCC的发病机制和早期预警仍有待进一步探索.以往研究认为,HBV相关HCC的发生主要是HBV基因片段整合后,X基因过度表达;而HCC与肝外组织,尤其是PBMC中HBV的研究较少,且多停留在基础研究阶段,以PBMC中HBV DNA检测为主,然而,PBMC中HBV DNA的检测不能准确区分HBV是在PBMC中存在还是在其细胞内复制.     

慢性乙型肝炎患者血清HBV DNA量与淋巴细胞亚群变化的关系

乙型肝炎是一种免疫相关性疾病,机体感染HBV后并不直接对肝细胞造成损伤,而是通过诱发机体免疫间接损伤肝细胞,同时机体产生免疫反应以清除病毒,这种免疫反应主要通过淋巴细胞亚群的改变来实现。本研究探讨慢性乙型肝炎患者HBV DNA定量与淋巴细胞亚群变化的关系。     

乙型及丙型肝炎患者发生肝细胞癌的风险预测：REVEAL-HBV/HCV研究的回顾

乙型肝炎病毒（HBV）及丙型肝炎病毒（HCV）的慢性感染是肝细胞癌（HCC）的主要致病原因。全球约有3亿5千万人为HBV的慢性感染者;HCV慢性感染者则有2亿人。全球每年约有50万人死于乙型肝炎引起的HCC,另有25万人死于丙型肝炎引起的HCC。乙型肝炎慢性感染者,其血中HBV DNA及ALT持续处于高水平是HCC最重要的预测因子。其他的危险因子还包括HBV C基因型、HBV基础核心促进子A1762T/G1764A双突变、男性、老年、肝癌家族史、酗酒习惯、以及与HCV或人类免疫不全病毒的合并感染等。根据REVEAL-HBV研究的资料,我们发展出简单易用的列线图,可利用非侵入性的临床特征准确地预测慢性乙型肝炎患者发生HCC的风险。丙型肝炎慢性感染患者发生HCC最重要的预测因子包括高血中HCV RNA水平、高ALT水平、HCV基因型以及老年等。REVEAL-HCV研究案例中,与HCV RNA水平低于检测范围且低ALT水平者相比,HCV RNA可测得、高ALT水平且感染第一型病毒的案例具有最高的HCC发生风险,其多变项调整后的风险比值（95%CI）为21.87（5.09～93.95）,这些发现对于慢性丙型肝炎的临床处置具有重要的意义。     

乙型肝炎病毒X蛋白通过氧化应激引起Raf-1线粒体转位

HBV慢性感染是诱发肝细胞癌(HCC)的首要因素之一,在HBV DNA的开放读码区S、C、P、X中,HBx基因及其所编码蛋白与HCC的关系最为密切[1],但它在转录活化中的具体机制和对病毒生命周期的影响的确切机制仍未明了,有待更深入的研究.而Raf-1作为原癌基因,对肿瘤的形成和发展起着重要作用,在促进肿瘤细胞增殖的同时,作为抗凋亡基因,阻止细胞凋亡的发生[2].本研究试图探讨HBx诱导Raf-1线粒体转位的现象及其机制.     

干扰素治疗慢性乙型肝炎的分子机制研究进展

IFN-α治疗慢性乙型肝炎的反应不仅与治疗前HBV DNA载量、HBV基因型、HBV基因组的点突变以及宿主Ⅱ类HLA基因的多态性等因素有关, 而且也与患者免疫状况有关, 病毒突变株及基因表型日益受到关注. IFN抗HBV的作用机制及HBV逃逸IFN治疗的机制尚未完全明确. 本文从基因、蛋白质和细胞等方面对相关影响因素及机制进行综述.     

乙型肝炎病毒X蛋白与原发性肝癌

原发性肝癌(HCC)是目前世界上十大恶性肿瘤之一, 而慢性乙型肝炎病毒(HBV)感染是导致HCC最主要的原因之一. 由HBV X基因编码的X蛋白(HBx)是一种重要的调节蛋白, 在HBV诱发HCC过程中扮演重要角色, 因此一直是研究的热点. 本文就近年有关HBx在HCC发生中的作用及作用机制作一综述.     

云南地区慢性乙型肝炎病毒感染者病毒基因型、变异与肝细胞癌的关系

大量研究表明,HBV感染所致的肝细胞癌(hepatocellutar carcinoma,HCC)占全球HCC的75％～85％,但HBV导致HCC的具体发生机制尚未完全阐明[1].目前普遍认为HBVC基因型引起的炎性坏死及纤维化程度比B型更严重,且C型与肝硬化和HCC有关;B基因型的累积生存率要明显高于C型.近年来国内外学者对HBV基因型、变异位点与HCC关系进行了大量研究,云南地区近年也有关于HBV基因型分布的研究报道,但是关于HBV基因型、变异与HCC关系的研究尚鲜见报道.本研究旨在了解云南地区慢性HBV感染者病毒基因型及变异情况,探讨慢性HBV感染者病毒基因型、常见位点变异与HCC的关系.     

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.