慢性乙型肝炎患者ALT、HBV DNA及血清肝纤维化标志物与肝纤维化程度的关系

目的探讨ALT、HBV DNA以及血清纤维化标志物透明质酸(HA)、层粘连蛋白(LN)、Ⅲ型前胶原肽(PⅢP)、Ⅳ型胶原(CⅣ)与慢性乙型肝炎肝纤维化程度的关系。方法检测281例慢性乙型肝炎患者血清中ALT、HBV DNA和纤维化标志物(HA、LN、PⅢP及CⅣ)的水平,并行肝活检检测肝组织病理纤维化分期。结果 HBeAg阴性慢性乙型肝炎患者HBV DNA水平较低、纤维化程度较高。HBeAg阳性患者纤维化程度与HBV DNA呈负相关(r=-0.251,P<0.001),S≥3组水平最低。慢性乙型肝炎患者纤维化程度与PⅢP水平呈正相关,其水平随着纤维化程度的加重而明显升高。结论 PⅢP水平可能作为评估慢性乙型肝炎患者肝纤维化程度的血清学指标,血清HBV DNA与肝脏纤维化严重程度的关系仍需进一步深入探讨。     

轻度慢性乙型肝炎患者肝组织纤维化与临床的相关性分析

目的探讨轻度慢性乙型肝炎(chronic hepatitis B,CHB)患者肝组织纤维化程度分期与临床的相关性。方法选取59例(HBe Ag阳性45例,HBe Ag阴性14例)轻度CHB患者为研究对象。所有患者均行B超检查,并进行肝穿刺活检,光镜下观察样本,将病理结果与血清ALT、AST、HBV DNA、肝纤维化标志物透明质酸(HA)及B超检查记录的肝脏门静脉(MPV)宽度进行对比分析。结果 HBe Ag阳性的轻度CHB患者HBV DNA中位滴度为8.3×107copies/ml,HBe Ag阴性的轻度CHB患者HBV DNA中位滴度为3.2×105copies/ml,两组比较,差异有统计学意义(P=0.011)。血清ALT、AST、HA值及MPV宽度在HBe Ag阳性和HBe Ag阴性的轻度CHB患者之间比较,差异均无统计学意义(P0.05)。两组患者中,肝组织纤维化分期分别与HA值、MPV宽度呈正相关(HA:r=0.533、P=0.023和r=0.702、P=0.046;MPV:r=0.546、P=0.044和r=0.762、P=0.028);而与血清ALT、AST及HBV DNA水平均无相关性(P0.05)。结论 HBV DNA滴度在HBe Ag阳性的轻度CHB患者中升高;轻度CHB患者的肝组织纤维化程度与HA值及MPV宽度有一定的相关性。     

慢性乙型肝炎患儿HBV DNA载量与肝脏病理、肝功能、肝纤维化血清学指标的相关性分析

目的探讨慢性乙型肝炎(CHB)患儿HBV DNA载量与肝脏病理及肝功能、肝纤维化血清学指标的关系。方法收集2010年7月-2015年6月湖南省儿童医院肝病中心收治的确诊为CHB的患儿79例,根据患儿血清HBV DNA载量分为低载量组(103拷贝/mlHBV DNA载量≤105拷贝/ml,n=8)、中载量组(105拷贝/mlHBV DNA载量≤107拷贝/ml,n=54)和高载量组(107拷贝/mlHBV DNA载量,n=17),比较各组间肝脏病理变化程度及血清ALT、AST、Ⅲ型前胶原(PCⅢ)、层黏连蛋白(LN)、透明质酸(HA)、Ⅳ型胶原CⅣ水平。计量资料组间比较采用Kruskal-Wallis秩和检验,相关性分析采用Kendall's tau-b等级相关检验。结果 3组肝脏病理炎症程度分级均以G1为主,分别占75%、74.1%、64.7%,高载量组G2比例上升(35.5%);3组肝组织纤维化分期均以S1为主,分别占75.0%、72.2%、70.6%,低载量组出现S4(12.5%)。HBV DNA载量与肝组织炎症分级和纤维化分期均无相关性(r值分别为0.069、-0.047,P值均0.05)。随着HBV DNA载量的增高,各组间血清ALT、AST水平逐渐增高,3组间ALT水平比较差异有统计学意义(χ2=5.37,P=0.048)。随着HBV DNA载量的增高,各组间血清HA、LN、PCⅢ和CⅣ水平则逐渐降低,3组间PCⅢ水平比较差异有统计学意义(χ2=6.26,P=0.044)。结论 CHB患儿HBV DNA载量与肝脏病理无显著相关性。临床综合分析HBV DNA载量及肝功能、肝纤维化血清学指标,结合肝活组织病理检查,才能更加客观、准确地评估CHB的病情。     

碱性成纤维细胞生长因子与慢性乙型肝炎及肝纤维化临床检测指标的关系

目的观察碱性成纤维细胞生长因子(b-FGF)在不同肝纤维化分期(S)肝组织中表达的差异性及其与临床检测常用的肝功能指标、肝纤维化指标、HBV DNA复制水平以及肝硬化Child-Pugh分级之间的关系。方法选取122例HBV引起的慢性肝炎及肝硬化患者,空腹静脉血检测:(1)肝功能指标:ALT、TBil、Alb;(2)肝纤维化指标:透明质酸(HA)、Ⅲ型前胶原(PCⅢ)、层粘连蛋白(LN)、Ⅳ型胶原(CⅣ);(3)HBV DNA复制水平;(4)对临床诊断肝硬化患者计算其Child-Pugh评分。行肝脏穿刺活检术后,经病理作纤维化分期(S1～S4)。免疫组织化学法测定肝组织中b-FGF在不同病理分期的表达及定位特点,半定量分析法计算b-FGF值,观察b-FGF与肝功能指标、肝纤维化指标、HBV DNA水平以及肝硬化Child-Pugh分级之间的关系。结果 (1)肝纤维化S1～S4期肝组织中b-FGF的表达部位及水平不同;(2)肝纤维化S1～S4期肝细胞中b-FGF的表达与肝纤维化分期(S1～S4)呈显著正相关(r=0.542,P<0.01);(3)不同肝纤维化分期中b-FGF的表达差异与患者ALT、TBil及Alb进行比较,其差异无统计学意义(P>0.05),不同肝纤维化分期患者,进行HBV DNA检测,其差异无统计学意义(P>0.05);(4)不同肝纤维化分期中,b-FGF与血清纤维化指标HA、PCⅢ、LN、CⅣ之间呈正相关;(5)b-FGF的表达与临床Child-Pugh分级无明显相关性。结论 b-FGF的表达与肝脏纤维化程度、肝纤维化指标有正相关关系,与患者ALT、TBil、Alb、Child-Pugh评分、及HBV DNA水平无关。     

ALT正常和轻度升高慢性HBV感染者的年龄与肝组织病理及HBVDNA定量的相关分析

目的探讨不同年龄的ALT正常和轻度升高慢性HBV感染者的肝组织病理及HBV DNA定量的特点。方法对2005年1月至2013年12月石家庄市第五医院收治的1123例ALT正常和轻度升高且行肝穿刺活组织检查的慢性HBV感染者进行回顾性分析,依据年龄分为40岁和≥40岁两组,分析两组中HBe Ag阳性与阴性及ALT正常与轻度升高患者的肝组织病理炎症分级(G)和纤维化分期(S)分布特点,并进行年龄与炎症分级、纤维化分期、HBV DNA定量的相关性分析。计量资料组间比较采用t检验,计数资料组间比较采用χ2检验,采用Spearman进行等级相关分析。结果与40岁组相比,≥40岁组患者肝组织炎症分级≥G2的比例明显增高,差异均有统计学意义(P值均0.001);无论是HBe Ag阳性还是HBe Ag阴性,ALT水平正常或轻度升高的患者均随着年龄增大其肝纤维化分期在≥S2所占比例明显增多,差异均有统计学意义(P值均0.001);年龄与炎性分级、纤维化分期均呈正相关(r值分别0.219、0.293,P值均0.001);≥40岁组中HBe Ag阴性、ALT轻度升高的患者其HBV DNA定量与40岁组患者相比,差异具有统计学意义(P0.05)。结论 ALT正常和轻度升高慢性HBV感染者肝组织炎症分级、纤维化分期均随年龄的增加有所增加,可考虑将年龄作为病情进展的因素之一。     

慢性乙型肝炎患者肝组织学纤维化分期与血清肝纤维化相关指标的关系

目的 探讨慢性乙型肝炎(CHB)肝组织学纤维化程度与临床血清肝纤维化相关指标之间的关系.方法 对189例人院诊断为CHB的患者行肝穿刺.同时检测血清HA、LN、PCⅢ、ⅣC、肝功能和血常规,并按组织学的不同纤维化分期(S)进行比较和相关性回归分析.结果 从肝纤维化So至S4期,PC Ⅲ、γ-GT、TBil、γ-球蛋白和PT渐增,差异有统计学意义(F值分别为3.325、6.218、2.958、10.160和7.028,P＜0.05);胆碱酯酶(CHE)、总蛋白(TP)、Alb、PLT值渐减,差异有统计学意义(F值分别为15.984、3.786、14.919和4.737,P＜0.01);LN、ⅣC、ALT和AST值在S各期比较差异有统计学意义(F值分别为4.618、2.795、2.649和3.199,P＜0.05).S分期与LN、PCⅢ、ALT、AST、TBil、γ-GT、γ-球蛋白、PT呈正相关(rs值为0.200、0.306、0.1 72、0.273、0.153、0.402、0.415、0.269),与CHE、TP、Alb、PLT呈负相关(rs值为-0.502、-0.208、-0.413、-0.390);LN、ALT、CHE、PLT、γ-球蛋白为肝纤维化分期的独立影响因素(P＜0.05).结论 肝组织学纤维化分期与血清肝纤维化、肝功能、血常规指标有不同程度相关.综合多项临床资料可早期无创性诊断肝纤维化.     

血清肝纤维化指标与肝脏病理学对照观察

目的评价血清肝纤维化指标对于诊断肝脏纤维化的临床价值。方法84例肝穿确诊的慢性乙型肝炎患者,检测透明质酸(HA)、Ⅳ型胶原(Ⅳ-C)、Ⅲ型前胶原肽(PⅢP)、层黏连蛋白(LN)水平。对肝组织纤维化病理分期与血清纤维化指标进行对比分析。结果Ⅳ-C、HA、PⅢP、LN与肝组织纤维化病理分期的相关系数分别为0.672(P<0.01)、0.316(P<0.01)、0.374(P<0.05)、0.066(P>0.05)。除LN外,其余指标水平均随着肝组织纤维化程度的加重而逐渐上升,且Ⅳ-C、HA、PⅢP的S3、S4期水平与S1、S2期比较有统计学差异(P<0.01)。S4期作为早期肝硬化诊断标准,通过ROC曲线分析Ⅳ-C、HA、PⅢP、LN的曲线下面积分别为0.901、0.764、0.756、0.434。敏感度:Ⅳ-C>PⅢP>HA>LN;特异度:HA>Ⅳ-C>PⅢP>LN。结论血清肝纤维化指标对肝组织病理纤维化程度的判断有指导意义。     

血清肝纤维化标志物水平与肝组织炎症活动度纤维化程度的相关性分析

研究血清纤维化指标透明质酸(HA)、层粘连蛋白(LN)、Ⅲ型前胶原(PCⅢ)及Ⅳ型胶原(Ⅳ-C)水平与肝组织病理分级、分期的相关性。用放射免疫法(RIA)检测600例乙型肝炎和肝炎肝硬化患者血清HA、LN、CⅣ、PCⅢ水平,同时进行肝组织活检,对肝组织进行炎症分级和纤维化分期检测。血清学指标水平与慢性肝炎发展阶段性一致,与肝组织炎症活动度及纤维化程度呈正相关。其中HA、CⅣ在病理分期中,从S1～S4期均依次大幅度升高,与S0相比(P<0.01),对早期肝纤维化诊断优于LN。而PCⅢ在反映肝纤维化时与S2期呈依次明显升高,可作为肝纤维化中、晚期辅助诊断。血清纤维化指标HA、LN、CⅣ、PCⅢ水平,对肝纤维化不同阶段做出相对准确的诊断,是目前了解肝纤维化程度检测指标之一。     

血清纤维化指标对肝纤维化诊断价值的研究

目的评价血清纤维化指标透明质酸（HA）、Ⅳ型胶原（CⅣ）、Ⅲ型前胶原肽（PⅢP）、层黏连蛋白（LN）对肝纤维化诊断的价值.方法对确诊的慢性乙型肝炎患者50例和健康人18例,测定血清纤维化指标水平,并进行肝组织纤维化分期.根据受试者工作特征曲线判别4项指标对于肝纤维化分期的诊断价值.结果血清HA、CⅣ、PⅢP和肝脏组织炎症分级呈较弱正相关（r分别为0.430、0.382和0.300,P＜0.05）.血清HA、CⅣ与肝脏组织纤维化分期呈中度正相关（r分别为0.614、0.708,P＜0.05）.血清HA、CⅣ水平随肝纤维化的进展程度而升高.血清HA诊断早期肝硬化（S4）的受试者工作特征曲线下面积（AUC）大于血清CⅣ、PⅢP和LN（AUC=0.967比0.932、0.659、0.403）.血清CⅣ诊断肝纤维化（S1～S4）的AUC大于血清HA、PⅢP和LN（AUC=0.853比0.680、0.536、0.487）.血清LN对于肝组织分级或分期均无统计学意义.联合HA＋CⅣ检测比单一指标有更高的特异度.结论血清纤维化指标对肝纤维化进程有一定的预测意义,但不能对肝纤维化精确分期,因此不能取代肝组织病理活检.联合多项指标检测可在一定程度上提高检测效率.寻找新的血清标志物和联合其他标志物是肝纤维化无创性研究的趋势所在.     

血清肝纤维化指标与肝脏病理学对照观察

目的评价血清肝纤维化指标诊断肝纤维化病理分期的临床价值。方法73例肝穿刺确诊的慢性乙型病毒性肝炎患者，同时进行血清HA、Ⅳ—C、PⅢP、LN的检测。以肝活检组织纤维化病理分期为金标准对以上血清学指标的诊断价值进行分析。结果HA、Ⅳ—C、PⅢP、LN与纤维化分期的相关系数分别为0.302（P〈0.01）、0．663（P〈0.01）、0.346（P〈0.05）、0.056（P〉0.05）。除LN外，其余指标血清水平均随着肝纤维化程度的加重而逐渐上升，其中HA、Ⅳ—C、PⅢPS3、S4期血清水平与S1期比较差异有非常显著性（P〈0.01）。S4期作为早期肝硬化诊断标准时，通过ROC曲线分析HA、Ⅳ—C、PⅢP、LN的曲线下面积分别为0.745、0．909、0.732、0.425。敏感度Ⅳ—C〉PⅢP〉HA〉LN；特异度HA〉Ⅳ—C〉PⅢP〉LN。结论可以认为血清肝纤维化指标对肝脏纤维化程度的判断有一定的指导意义。     

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.