核苷(酸)类似物联合干扰素治疗HBeAg阳性慢性乙型肝炎120周的疗效随访

目的 观察核苷(酸)类似物联合干扰素延长疗程至96周治疗HBeAg阳性慢性乙型肝炎,随访24周的疗效. 方法 135例HBeAg阳性慢性乙型肝炎患者,90例接受核苷(酸)类似物联合干扰素治疗(联合治疗组),45例接受单一核苷(酸)类似物治疗(对照组).分别在治疗12、24、48、72、96周及随访24周时进行生物化学、病毒学、血清学评估.应答疗效比较采用x2检验. 结果 135例患者纳入分析.联合治疗组90例完成96周疗程后,17例(占18.9％)患者发生HBsAg血清学转换,37例(占41.1％)患者发生HBeAg血清学转换;对照组无患者发生HBsAg血清学转换,15例(占33.3％)患者发生HBeAg血清学转换,联合治疗组HBsAg血清学转换明显高于对照组,x2=8.08,P＜ 0.01,差异有统计学意义.两组患者HBeAg血清学转换差异无统计学意义.出现HBsAg血清转换＜ 30岁为64.7％ (11/17),30 ～ 40岁为9.7％(6/62),＞40岁11例中无一例出现HBsAg血清转换,＜ 30岁患者HBsAg血清转换率明显高于其他年龄组,x2值分别是12.62和4.24,P值均＜0.05,差异有统计学意义. 结论 核苷(酸)类似物联合干扰素延长疗程治疗HBeAg阳性慢性乙型肝炎能提高HBsAg血清学转换,年龄＜30岁者出现HBsAg血清学转换比例最高.     

慢性乙型肝炎患者拉米夫定治疗后血清HBsAg阴转2例

我们使用拉米夫定抗病毒治疗的慢性乙型肝炎患者中,有1例患者血清HBsAg阴转,1例患者HBsAg血清转换,出现抗-HBs阳性,现报道如下.     

慢性乙型肝炎抗病毒治疗HBVDNA阴转后HBeAg血清学转换的分析

目的探讨使用核苷(酸)类似物(NAs)对慢性乙型肝炎HBeAg阳性患者抗病毒治疗HBV DNA阴转后,根据HBeAg变化情况,指导后期的治疗用药,预测停药的时间及可能性。方法选取2000年1月至2016年1月期间门诊及住院口服NAs 6年以上且资料完整的慢性乙型肝炎HBeAg阳性患者63例作为研究对象,分析HBV DNA阴转6年后,HBeAg转阴例数及HBeAg血清学转换率;出现耐药与未出现耐药组、肝硬化与慢性乙型肝炎组的HBeAg转阴及HBeAg血清学转换例数。并按初治单用拉米夫定者、阿德福韦酯者、恩替卡韦者分为3组,了解在HBV DNA阴转6年后,HBeAg转阴及血清学转换例数。结果 (1)63例患者在HBV DNA阴转6年后,HBeAg转阴例数为23例,阴转率36.5%,血清学转换率11.1%;初治单用恩替卡韦组HBeAg转阴例数最多,但差异无统计学意义(P0.05);初治单用恩替卡韦组HBeAg血清学转换例数最多,3组在HBeAg血清学转换上差异有显著统计学意义(P0.01)。(2)出现耐药与未出现耐药组患者HBeAg转阴及血清学转换差异有显著统计学意义(P0.01),提示未出现耐药的患者HBeAg转阴及血清学转换明显高于出现耐药的患者。(3)治疗前肝硬化与慢性乙型肝炎组患者HBeAg转阴及血清学转换例数差异无统计学意义(P0.05)。结论 HBeAg阳性的慢性乙型肝炎患者服用NAs抗病毒治疗,在HBV DNA阴转后,通常需要4至6年的继续抗病毒治疗,才能达到HBeAg血清学转换,才有停药的可能。     

拉米夫定治疗慢性乙型肝炎90例

目的:观察拉米夫定对血清HBsAg、HBeAg、HBV DNA阳性的慢性乙型肝炎患者的疗效。方法:180例HBsAg、HBeAg、HBV DNA阳性的慢性乙型肝炎患者随机分成对照组(90例)和治疗组(90例)。对照组采用一般保肝、降酶综合治疗;治疗组在对照组综合治疗基础上每日口服拉米夫定100mg,疗程1年。结果:对照组、治疗组患者ALT复常率分别为77例(85.6％)、79例(87.8％),两组差异无显著性意义(P>0.05)。对照组7例(7.8％)血清HBV DNA阴转,5例(5.6％)血清HBeAg阴转,2例(2.2％)出现HBeAg/抗-HBe血清转换;治疗组78例(86.7％)血清HBV DNA阴转,64例(71.1％)血清HBeAg阴转,44例(48.9％)出现HBeAg/抗-HBe血清转换;两组差异有非常显著性意义(P<0.005～P<0.001)。结论:拉米夫定能有效抑制HBV DNA复制,促使患者HBeAg转阴、HBBeAg/抗-HBe血清转换;但也有部分病例治疗无效和出现YMDD病毒变异。     

免疫耐受期慢性乙型肝炎儿童抗病毒治疗临床随访

目的评估免疫耐受期慢性乙型肝炎儿童抗病毒治疗的长期临床获益。方法对前期随机对照临床试验纳入的46例治疗组免疫耐受期慢性乙型肝炎儿童进行长期随访,在临床试验开始后的第108、120、132、144、168、192周分别对患者进行临床评估。结果 46例患者均完成随访。随访结束(第192周)与临床试验完成时(临床试验开始后第96周)相比较,血清HBV DNA阴转增加3例,血清HBeAg阴转增加7例,HBeAg抗体转换增加6例,血清HBsAg阴转例数无变化,HBsAg抗体转换例数增加3例,总计分别为37例(80.4%)、22例(47.8%)、21例(45.7%)、10例(21.7%)、10例(21.7%)。9例(19.6%)未达到HBV DNA阴转,停药后均出现病毒学突破。结论免疫耐受期慢性乙型肝炎儿童抗病毒治疗需要更大样本量的研究深入论证。     

提高HBeAg阳性慢性乙型肝炎患者的HBeAg血清学转换率的治疗对策

乙型肝炎病毒e抗原(HBeAg)阳性的慢性乙型肝炎患者自发地或治疗后出现HBeAg血清学转换,伴有血中HBVDNA的下降、丙氨酸转氨酶(ALT)恢复正常、临床病情的缓解、肝脏组织炎症活动度减轻,部分患者在HBeAg血清学转换后可出现乙肝肝炎病毒表面抗原(HBsAg)的血清学转换,是HBeAg阳性慢性乙型肝炎的治疗目标[1].     

替比夫定治疗高ALT水平HBeAg阳性慢性乙型肝炎的临床观察

目的观察替比夫定治疗高ALT水平HBeAg阳性慢性乙型肝炎（CHB）患者的疗效。方法 60例HBeAg阳性的CHB患者以ALT为依据分为低ALT组（ALT在2倍ULN与10倍之间）和高ALT组（ALT在10倍ULN与20倍之间）,给予替比夫定600 mg/d,观察治疗52周时的应答情况。结果治疗52周时,高ALT组HBV DNA降低比例明显高于低ALT组,差异有统计学意义;低ALT组HBeAg阴转率及血清学转换率、HBsAg阴转率低于高ALT组,差异有统计学意义;高ALT组中有4例出现HBsAg阴转,3例出现了HBsAb;低ALT组中没有出现HBsAg阴转及血清学转换。52周时两组患者ALT复常率、病毒学反弹、对替比夫定耐药及肌酸激酶升高水平相似。结论高水平ALT是替比夫定治疗应答较好的预测因子     

恩替卡韦治疗高ALT水平HBeAg阳性慢性乙型肝炎疗效观察

目的观察恩替卡韦治疗高ALT水平HBeAg阳性慢性乙型肝炎（CHB）患者的疗效。方法 60例HBeAg阳性的CHB患者以ALT为依据分为低ALT组（ALT在2倍ULN与10倍之间）和高ALT组（ALT在10倍ULN与20倍之间）,给予恩替卡韦0.5mg/d,观者治疗48周时的应答情况（HBV DNA阴转率,HBeAg/抗-HBe血清转换率,HBsAg/抗-HBs血清转换率和ALT复常率）。结果治疗48周时,高ALT组HBV DNA阴转率为95.0%,低ALT组为75.0%,差异有统计学意义（P=0.0225）;低ALT组HBeAg阴转率、HBeAg血清学转换率、HBsAg阴转率、HBsAg血清学转换率依次为25.0%、25.0%、0.0%、0.0%,均明显低于高ALT组的55.0%、45.0%、15.0%、15.0%,差异有统计学意义（P=0.0184,0.0302,0.0015,0.0012）;高ALT组中有3例出现HBsAg阴转,3例出现了HBsAb;低ALT组中没有出现HBsAg阴转及血清学转换。48周时两组患者ALT复常率、病毒学反弹、对恩替卡韦耐药及药物不良反应水平相似。结论高水平ALT是恩替卡韦治疗应答较好的预测因子。     

慢性乙型肝炎免疫耐受期的抗病毒治疗:系统综述

目的系统评价抗病毒治疗在免疫耐受期慢性乙型肝炎(CHB)患者中的有效性和安全性。方法检索PubMed、EMBASE、Cochrane library、中国知网、万方数据库自数据库建立至2020年9月抗病毒药物治疗免疫耐受期CHB的临床试验,进行质量评价后提取相关效应量并进行系统评价。主要结局指标为HBV DNA阴转率。结果共纳入9项研究821例患者。8项研究报道了治疗组中HBV DNA阴转率,6项研究中治疗组HBV DNA阴转率均超过60%,明显高于未治疗患者(0～29.1%),且联合治疗组优于单药治疗组。但在长期观察中,病毒学复发较常见。8项研究报告了HBeAg血清学转换,仅2项IFNα治疗儿童的研究中治疗组血清学转换率超过20%,高于未治疗组。HBsAg阴转出现在2项使用IFNα治疗的研究中,无研究观察到HBsAg血清学转换。1项研究报告了肝硬化和肝细胞癌(HCC)的风险,显示抗病毒治疗可降低患者肝硬化和HCC的风险。不良反应发生率在核苷(酸)类似物治疗中为4.1%～13.0%,在IFNα治疗中达到了100%,严重不良反应少见。结论免疫耐受期CHB患者给予抗病毒后绝大多数可出现满意的病毒学应答,但停药后易复发,且血清学转换率低。抗病毒治疗安全性良好。目前证据表明,对于该类患者如无明确疾病进展可动态观察。     

拉米夫定与乙肝特异性主动免疫联合疗法治疗慢性乙型肝炎病毒携带者的前瞻性临床研究

目的　对拉米夫定与乙肝特异性主动免疫联合疗法治疗慢性乙型肝炎病毒携带者的临床效果。方法 10 0例慢性乙型肝炎病毒携带者 ,随机分为联合治疗组 ( 5 0例 )用拉米夫定 10 0mg/日 ,加用乙肝特异性主动免疫联合疗法每 4周 1次 ,疗程为 48周 ;对照组为拉米夫定单一治疗 ( 5 0例 ) ,用拉米夫定 10 0mg/日 ,口服。结果　联合治疗组HBsAg阴转率 ( 18%) ,抗 HBs阳转率为 6%,而拉米夫定单一治疗组分别为 4%和 0 %,P <0 .0 0 1;联合治疗组HBeAg阴转率 40 %以及HBeAg血清学转换 (HBeAg消失、抗 HBe阳转 )率为 3 0 %,均高于拉米夫定单一治疗组 ,P <0 .0 5。结论　拉米夫定与乙肝特异性主动免疫联合疗法的疗效优于单一口服拉米夫定疗法     

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.