慢性乙型肝炎合并非酒精性脂肪性肝病患者抗病毒治疗的疗效探讨

目的对慢性乙型肝炎（CHB）合并非酒精性脂肪性肝病（NAFLD）患者抗病毒治疗疗效进行回顾性分析,探讨肝细胞脂肪变是否影响CHB患者抗病毒的疗效。方法收集2004年1月至2011年12月在本院进行抗病毒治疗的110例CHB患者,CHB合并NAFLD患者99例,采用荧光定量PCR法检测血清HBV DNA水平,用化学发光法检测血清乙型肝炎两对半定量,采用全自动生物化学分析仪检测肝功能。计数资料采用χ2检验,计量资料采用t检验。结果 （1）干扰素抗病毒治疗时,24周单纯CHB患者较合并脂肪肝患者生化学应答率更高（χ2=4.069,P=0.044）;48周HBV DNA阴转率明显优于后者（χ2=17.327,P=0.000）。对于HBeAg阳性患者,单纯CHB患者在24周的生化学应答率、24和48周时的HBV DNA阴转率、HBeAg阴转率均显著优于合并脂肪肝患者,两者比较差异具有统计学意义（P〈0.05）,48周时两组的生化学应答差异无统计学意义（P〉0.05）。（2）核苷和核苷酸类药物抗病毒治疗时,48周单纯CHB患者的生化学应答率较高（χ2=7.620,P=0.006）,24和48周的HBV DNA阴转率差异无统计学意义。对于HBeAg阳性患者,24周时合并脂肪肝组患者的HBeAg转阴率高于单纯CHB患者,48周时ALT/AST复常率低于单纯CHB患者,差异均具有统计学意义（P〈0.05）,24周ALT/AST复常率、HBV DNA转阴率、48周HBV DNA转阴率、HBeAg转阴率差异均无统计学意义（P〉0.05）。结论肝细胞脂肪变对CHB患者的抗病毒治疗效果存在一定的影响。     

慢性乙型肝炎患者干扰素治疗前后血清IL-7及调节性T细胞的变化

目的研究慢性乙型肝炎患者干扰素治疗前后血清IL-7及调节性T细胞的变化。方法本研究共有慢性乙型肝炎(CHB)患者67例,慢性乙型肝炎病毒(HBV)携带者18例,健康对照者14例。CHB组患者予以派罗欣(聚乙二醇干扰素α-2a注射液180μg,1次/周)抗病毒治疗24周,治疗结束后,按HBV-DNA定量不同再分为完全应答组(16例)、部分应答组(15例)和无应答组(36例);HBV携带组和健康组不做任何治疗。分别于0周、24周检测外周血IL-7、CD4+CD25+调节性T细胞百分比。结果在0周时,外周血IL-7含量和CD4+CD25+调节性T细胞在完全应答组、部分应答组及无应答组比较,差异均无统计学意义(P0.05);24周时,完全应答组与部分应答组、无应答组间比较,差异均有统计学意义(P0.05);完全应答组治疗前后比较,差异也有统计学意义(P0.05)。结论慢性乙型肝炎患者干扰素治疗后血清IL-7升高,调节性T细胞降低,可能与病毒应答有关。     

聚乙二醇干扰素α-2α联合胸腺肽 α1治疗对慢性乙型肝炎患者生存质量的影响

目的 探讨聚乙二醇干扰素（PEG-IFN）α-2a联合胸腺肽α1（Tα1）治疗对慢性乙型肝炎（CHB）患者生存质量（QOL）的影响.方法 选择2008年10月至2012年10月本科收治的CHB患者148例,随机分为观察组和对照组各组74例,对照组采用PEG-IFNα-2a治疗;观察组采用PEG-IFNα-2a联合Tα1治疗,比较分析两组患者治疗3、6、12个月时HBV DNA载量的变化情况,QOL及慢性肝病问卷（CLDQ）评分和不良反应.组间比较采用独立样本t检验,治疗前后比较采用配对t检验,计数资料比较采用χ2检验.结果 观察组治疗3、6、12个月时HBV DNA载量下降值和病毒学应答率均明显高于对照组（t=2.281,P=0.02;χ2=3.950,P=0 04;t=3 237,P=0.00;χ2=4.022,P=0.04;t=3.197,P=0.00; χ2=4.028,P=0.04）;观察组治疗6个月时总的QOL、生理、社会关系评分及乏力、焦虑评分明显高于对照组（t=2.039~3.472,P＜0.05）;观察组治疗12个月总的QOL、总的健康状况、生理、心理、社会关系评分及乏力、全身症状、活动、焦虑、环境评分明显高于对照组（t=2.020～3.201,P＜0.05）.结论 PEG-IFNα-2a联合Tα1治疗CHB可增强患者机体免疫力及抗病毒能力,提高机体清除HBV的能力,从而提高患者生存质量,值得临床推广.     

恩替卡韦治疗慢性乙型肝炎患者血清IL-4和IL-10水平变化

目的：探讨恩替卡韦（ETV）对慢性乙型肝炎（CHB）患者血清白细胞介素4（IL-4）和白细胞介素-10 （IL-10）水平的影响及其临床意义.方法：检测健康对照人群及CHB患者恩替卡韦抗病毒治疗24周前后血清ALT、HBV DNA、IL-4及IL-10的浓度,分析治疗前后4种指标的变化情况.结果：CHB患者血清中IL-4和IL-10水平高于健康对照组,差异有统计学意义（P均＜0.05）;CHB患者血清中ALT、HBV DNA、IL-4及IL-10水平在恩替卡韦抗病毒治疗后较治疗前均下降,差异有统计学意义（P均＜0.05）.结论：恩替卡韦能有效抑制HBV复制,降低CHB患者血清IL-4和IL-10的水平,并减轻肝脏炎症,改善CHB患者的免疫功能.     

慢性乙型肝炎患者干扰素应答与外周血单核细胞IFN—α和IL-18表达的关系

目的分析慢性乙型肝炎（CHB）患者外周血单核细胞（PBMC）干扰素-α（IFN—α）及白细胞介素18（IL-18）mRNA的诱导表达差异，评价慢性乙型肝炎患者PBMC细胞免疫功能。方法对2004年6月至2005年5月华中科技大学同济医学院附属协和医院52例门诊和住院CHB患者，聚肌胞苷酸（PolyIC）体外刺激正常对照组和CHB组患者PBMC，取培养上清利用病毒保护试验测定IFN—α2b治疗前后PBMC表达的干扰素抗病毒生物学活性。同时用脂多糖（LPS）体外刺激不同组PBMC，RT—PCR检测PBMCIL-18 mRNA水平的变化。结果治疗前干扰素治疗应答组（n=13）和无应答组（n=27）PBMC分泌的干扰素生物学活性均显著低于对照组（n=20）（均P〈0．01）。应答组干扰素活性随治疗时间延长而增加，1个月时已显著高于无应答组（P〈0．01）；无应答组干扰素活性始终处于低下水平。治疗前，应答组和无应答组PBMC IL-18 mRNA水平也显著低于对照组（均P〈0．01）；治疗后，应答组IL-18 mRNA水平随治疗时间延长而升高，1个月时也著显高于无应答组（P〈0．01），无应答组IL-18 mRNA水平始终较低。PBMC IFN—α活性和IL-18 mRNA水平有良好的正相关性（r=0．922，P〈0．01）。结论慢性HBV感染患者的细胞免疫功能受损，不能正常表达IFN—α和IL-18，但应答组患者经干扰素治疗后表达能力逐渐恢复。     

慢性乙型肝炎患者外周血单个核细胞穿孔素表达与干扰素抗病毒疗效的关系

目的研究慢性乙型肝炎(CHB)患者干扰素(IFN)治疗前、后外周血单个核细胞(PBMC)中穿孔素表达情况,探讨其对IFN抗病毒疗效的影响。方法采用免疫细胞化学技术检测35例CHB患者IFNα-2b治疗前、后PBMC中穿孔索的表达。结果IFNα～2b治疗前、后PBMC穿孔素的表达分别为7．9%±4．6%和15．3%±6．4%,较治疗前明显上升,t=6．53,P＜0．01,差异有统计学意义。IFNα-2b治疗后完全应答者有12例、部分应答者14例、无应答者9例。IFN治疗后完全应答组穿孔索的表达为19．2%±5．2%,部分应答组为14．2%±5．5%,无应答组为11．7%±6．7%,完全应答组与部分应答组比较,t=2．33,P＜0．05；完全应答组与无应答组比较,t=2．89,P＜0．01,差异有统计学意义。结论CHB患者IFN治疗可以使PBMC中穿孔素的表达升高,PBMC中穿孔素的表达可能与IFN抗病毒疗效有密切的关系。     

慢性乙型肝炎：抗病毒治疗应答若干定义之比较及评价

在应用干扰素（IFN）或核苷／核苷酸类似物（NUC）对慢性乙型肝炎（CHB）进行抗病毒治疗时,需密切观察和评价患者的抗病毒治疗应答,以判断疗效和调整治疗方案。目前,对CHB抗病毒治疗应答的分类及相关定义存在较大混乱,甚至对同一术语的定义也存在明显差异,给临床带来了很大困惑。为此,本文特对2007年美国肝病学会（AASLD）指南、2008年美国部分肝病专家制订的CHB处理流程（以下简称keeffe流程）、2008年欧洲肝病学会（EASL）指南、2009年亚太地区肝病研究协会（APASL）共识及2005年中华医学会（CMA）肝病学分会和感染病学分会联合制订的CHB防治指南（以下泛称指南）中有关抗病毒治疗应答的定义进行了汇总、比较和评论,以期进一步提升对抗病毒治疗应答的思考和认识。     

化痰消脂方对慢性乙型肝炎并发非酒精性脂肪性肝病患者抗病毒治疗疗效的影响

目的观察化痰消脂方对慢性乙型肝炎（CHB）并发非酒精性脂肪性肝病（NAFLD）患者干扰素抗病毒治疗疗效的影响,并探讨其相关机制。方法随机将62例患者分成治疗组和对照组,各31例。治疗组给予化痰消脂方联合干扰素治疗,对照组单用干扰素治疗,观察两组患者治疗前后HOMA-IR、HBVDNA定量、HBV-M的变化及超声显示的脂肪肝改善情况。结果治疗组患者脂肪肝改善率、病毒应答率明显高于对照组（P〈0.01或P〈0.05）,HOMA-IR明显降低（P〈0.01）。结论化痰消脂方能明显提高CHB并发NAFLD患者的抗病毒应答率,其机制可能与改善此类患者脂肪肝及胰岛素抵抗状况有关。     

长效干扰素α-2a治疗慢性乙型肝炎过程中外周血浆样树突状细胞的变化及其与疗效的关系

目的 观察长效干扰素(PEG-IFN α-2a)治疗慢性乙型肝炎过程中外周血浆样树突状细胞(pDC)亚群的变化及其与临床疗效的关系. 方法 41例慢性乙型肝炎患者接受PEG-IFN α-2a(180 μg)每周皮下注射一次,治疗48周;治疗过程中检测肝功能、血清HBV病毒学标志物和HBVDNA,在治疗前及治疗开始后2、12、24、36、48周分别检测外周血pDC数量和功能及Toll样受体(TLR)9的表达水平、血清肿瘤坏死因子(TNF)α及IFN γ水平.对数据进行成组设计t检验、非参数检验、重复测量资料的方差分析. 结果 应答组与无应答组比较,TLR9平均荧光强度、pDC数量及INF α分泌能力在治疗2周时均明显下降,应答组在12周时TLR9平均荧光强度恢复(66.25±13.10),无应答组仍处于低水平(51.47±16.85),差异有统计学意义(t=2.478,P＜0.05);12周时应答组pDC数量恢复(5.24±1.61),无应答组为(3.74±1.25),差异有统计学意义(t=2.644,P＜0.05);12周时应答组IFN α分泌能力明显升高(459.94±200.27) pg/ml,显著高于无应答组[(237.18± 123.57)pg/ml],差异有统计学意义(t=2.942,P＜0.05).治疗24周时,应答组血清IFN γ水平明显升高[(67.81±16.64) pg/ml],显著高于无应答组[(43.73± 15.97) pg/ml],差异有统计学意义(t=3.396,P＜ 0.05);TNFα水平为[(268.94±64.32)pg/ml],也显著高于无应答组[(206.45±78.28) pg/ml],差异有统计学意义(t=2.22,P＜0.05).结论 pDC在PEG-IFNα-2a治疗诱发的早期免疫应答中发挥重要作用,抗病毒治疗过程中pDC数量和功能的恢复可能是机体抗病毒治疗应答的重要因素.     

平均血小板体积在慢性乙型肝炎合并非酒精性脂肪肝中的应用

目的 探讨平均血小板体积（MPV）对慢性乙型肝炎（CHB）合并非酒精性脂肪肝（NAFLD）的预测价值.方法 选择CHB患者77例,其中单纯CHB患者（CHB组）32例、CHB合并NFALD患者（CHB＋ NFALD组）45例、健康体检者33例（对照组）,比较各组BMI、HBV DNA载量、转氨酶、TC及MPV变化,分析MPV与CHB合并NFALD患者的相关性.结果 MCHB＋NAFLD组BMI、TC均高于对照组及CHB组（P＜0.05）,HBV DNA载量低于CHB组（P＜0.05）,ALT、AST水平均低于CHB组及对照组（P均＜0.05）.CHB组MPV高于对照组（P＜0.05）,CHB＋NAFLD组MPV高于CHB组（P＜0.05）.BMI、TC、MVP与CHB合并NFALD均存在正相关（OR值分别为3.714、6.624、8.45,P均＜0.05）.结论 MPV是CHB合并NFALD的独立危险因素之一.监测MPV有助于早期评估CHB患者发生NAFLD的风险.     

Three layer functional model and energy exchange concept of aging process

Relying on a certain degree of abstraction, we can propose that no particular distinction exists between animate or living matter and inanimate matter. While focusing attention on some specifics, the dividing line between the two can be drawn. The most apparent distinction is in the level of structural and functional organization with the dissimilar streams of ‘energy flow’ between the observed entity and the surrounding environment. In essence, living matter is created from inanimate matter which is organized to contain internal intense energy processes and maintain lower intensity energy exchange processes with the environment. Taking internal and external energy processes into account, we contend in this paper that living matter can be referred to as matter of dissipative structure, with this structure assumed to be a common quality of all living creatures and living matter in general. Interruption of internal energy conversion processes and terminating the controlled energy exchange with the environment leads to degeneration of dissipative structure and reduction of the same to inanimate matter, (gas, liquid and/or solid inanimate substances), and ultimately what can be called ‘death.’ This concept of what we call dissipative nature can be extended from living organisms to social groups of animals, to mankind. An analogy based on the organization of matter provides a basis for a functional model of living entities. The models relies on the parallels among the three central structures of any cell (nucleus, cytoplasm and outer membrane) and the human body (central organs, body fluids along with the connective tissues, and external skin integument). This three-part structural organization may be observed almost universally in nature. It can be observed from the atomic structure to the planetary and intergalactic organizations. This similarity is corroborated by the membrane theory applied to living organisms. According to the energy nature of living matter and the proposed functional model, the decreased integrity of a human body's external envelope membrane is a first cause of the structural degradation and aging of the entire organism. The aging process than progresses externally to internally, as in single cell organisms, suggesting that much of the efforts towards the restoration and maintenance of the mechanisms responsible for structural development should be focused accordingly, on the membrane, i.e., the skin. Numerous reports indicate that all parts of the human body, like: bones, blood with blood vessels, muscles, skin, and so on, have some ability for restoration. Therefore, actual revival of not only aging tissue of the human body's membrane, but the entire human body enclosed within, with all internal organs, might be expected. We assess several aging theories within the context of our model and provide suggestions on how to activate the body's own anti-aging mechanisms and increase longevity. This paper presents some analogies and some distinctions that exist between the living dissipative structure matter and inanimate matter, discusses the aging process and proposes certain aging reversal solutions.     

Unusual responses of nocturnal pineal melatonin synthesis and secretion to swimming: Attempts to define mechanisms

Abstract: The effect of swimming at night on rat pineal melatonin synthesis was compared with that of light exposure at night. Rats were forced to swim at 0030 hr (lights out at 2000 hr) and sacrificed by decapitation 15 and 30 min later, immediately after swimming. Other groups of animals were exposed to white light (650μW/cm²) for 15 and 30 min at same time. Swimming caused a rapid and highly significant drop in the melatonin content in the pineal gland; however, the activity of N-acetyltransferase (NAT), the supposed rate limiting enzyme in the melatonin production, was not changed. Despite the drop in pineal melatonin levels, serum concentrations of the indole remained elevated in the rats that swam. In contrast, melatonin levels in the pineal and serum of light exposed rats fell precipitously, accompanied by a significant suppression of NAT activity. Since we anticipated that the strenuous exercise associated with swimming may induce release of artrial natriuretic peptide (ANP) from the heart, which in turn could cause the release of pineal melatonin, in a second study we injected physiological saline intravenously to stretch the cardiac muscle and release ANP. Three milliliters of normal saline was injected during the day into the jugular vein of anesthetized rats that were pretreated with isoproterenol to stimulate pineal melatonin production. Animals were killed 15 min after the saline injection, and pineal NAT activity and pineal melatonin levels were measured. The saline injections caused no alteration in the elevated levels of either NAT or melatonin. These data suggest that the disparity in pineal NAT activity (which was high) and pineal melatonin (which was low), in animals swum at night, may not be caused by ANP which is released during strenuous exercise such as swimming.     

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.     

Melatonin and photoperiodic time measurement: Seasonal breeding in the sheep

Abstract: Well-established circadian physiology supports the view that photoperiodic time measurement utilizes the coincidence between the presence of light and a photosensitive phase of a 'biological clock' to alter reproductive status—the so-called external coincidence model of seasonal breeding. In this review, we examine the mechanism whereby photoperiod interacts with presumed suprachiasmatic nuclei activity to allow endogenous melatonin to normally synchronize reproductive activity to the optimal time of year. The Romney Marsh sheep is particularly explored as an experimental model. It is suggested that the on/off activity of seasonal reproduction may be a robust mechanism able to be predictably manipulated by the judicious use of the light/dark cycle and exogenous melatonin, but firmly based on circadian principles.     

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.