慢性乙型肝炎患者HBVDNA载量与肝组织炎症及纤维化程度的相关性分析

目的研究慢性乙型肝炎(CHB)患者血清HBV DNA载量与肝组织炎症及纤维化程度间的相关性。方法将169例CHB患者根据血清HBeAg分为HBeAg阳性组(110例)和HBeAg阴性组(59例),回顾性分析血清HBV DNA载量与肝组织病理炎症分级、纤维化分期之间关系。结果 HBeAg阳性组与HBeAg阴性组血清HBV DNA载量分别为(6.9±1.3)log10拷贝/ml和(4.7±1.8)log10拷贝/ml,两组比较差异有统计学意义(P=0.024)。HBeAg阳性组患者肝组织炎症活动度G1组为9例、G2组为80例、G3~4组为21例,其血清HBV DNA载量分别为(5.7±1.4)log10拷贝/ml、(6.4±1.8)log10拷贝/ml、(7.2±1.1)log10拷贝/ml,3组患者血清HBV DNA载量比较,差异无统计学意义(P=0.069)。肝组织纤维化程度S1组为28例、S2组为50例、S3~4组为32例,其血清HBV DNA载量分别为(6.9±1.1)log10拷贝/ml、(6.9±1.4)log10拷贝/ml、(6.8±4.2)log10拷贝/ml,3组患者血清HBV DNA载量比较,差异无统计学意义(P=0.079)。HBeAg阴性组患者肝组织炎症活动度G1组为6例、G2组为19例、G3~4组为34例,其血清HBV DNA载量分别为(2.2±1.9)log10拷贝/ml、(4.9±1.5)log10拷贝/ml、(5.4±1.8)log10拷贝/ml,3组患者血清HBV DNA载量比较,差异有统计学意义(P=0.014);肝组织纤维化程度S1组为12例、S2组为30例、S3~4组为17例,其血清HBV DNA载量分别为(2.6±4.1)log10拷贝/ml、(5.3±1.3)log10拷贝/ml、(5.6±1.7)log10拷贝/ml,3组血清HBV DNA载量比较,差异有统计学意义(P=0.026)。结论 HBeAg阳性CHB患者血清HBV DNA载量与肝组织炎症及纤维化程度无显著相关。HBeAg阴性CHB患者血清HBV DNA载量较高者,其肝组织炎症及纤维化程度较高。     

HBeAg阴性慢性乙型肝炎病毒感染者肝组织病理改变的相关因素分析

目的 分析HBeAg阴性慢性HBV感染者肝组织病理改变的相关因素.方法 对288例不同年龄、性别、ALT水平、肝组织HBsAg和HBcAg免疫组织化学结果的HBeAg阴性HBV感染者的HBV DNA载量、肝组织病理变化进行相关分析,采用Bivariate Pearson法.结果 男性组肝组织炎症分级和纤维化分期分别为1.721.23和1.71±1.24,女性组分别为1.25±1.39和1.21±1.40,两组差异有统计学意义(t=2.398,t=2.551;均P＜0.05)}男性HBV DNA载量高于女性,但差异无统计学意义.40岁以上HBeAg阴性HBV感染者HBV DNA载量、肝组织炎症分级和纤维化分期显著高于40岁以下者(t=2.060,t=2.536,t=2.808;均P＜0.05).ALT正常的HBeAg阴性乙型肝炎患者中,75例(52.03%)血清HBVDNA≤1×103拷贝/mL,肝组织炎症活动度≥G2的56例,占38.89%,血清ALT水平与肝组织炎症活动度相关(r=0.244,P=0.004).ALT异常的慢性HBV感染者中,42例(31.57%)血清HBV DNA≤1×103拷贝/mL,肝组织炎症活动度≥G2的89例,占66.92%.血清ALT水平与肝组织炎症程度无相关(r=0.007,P=0.939).肝组织免疫组织化学HBsAg及HBcAg双阳性组肝组织炎症/纤维化、HBV DNA滴度显著高于HBsAg、HBcAg双阴性组和HBsAg阳性、HBcAg阴性组,差异有统计学意义.血清HBV DNA与肝组织炎症程度相关(r=0.349,P＜0.05).结论 性别、年龄、血清HBV DNA水平及HBsAg、HBcAg免疫组织化学结果可作为判断HBeAg阴性慢性乙型肝炎患者肝组织炎症损伤程度的相关指标,男性、年龄越大、血清HBV DNA水平越高、肝组织免疫组织化学HBsAg及HBcAg双阳性,肝组织炎性反应损伤越严重.HBeAg阴性慢性乙型肝炎患者即使ALT正常、血清HBV DNA≤1×100拷贝/mL,仍约1/3患者的肝组织存在明显的炎性反应损伤,需定期追踪,最好行肝组织活检,以早期发现适宜治疗者而避免延误病情.     

血清HBsAg和HBV DNA预测慢性乙型肝炎肝组织病理状态的评价

目的 探讨血清乙型肝炎表面抗原（HBsAg）水平和乙型肝炎病毒DNA（HBV DNA）载量预测慢性乙型肝炎（CHB）肝组织炎症活动度和纤维化程度的效能.方法 472例经肝组织活检的CHB患者入选本研究,其中HBeAg阳性279例,HBeAg阴性193例.肝组织病理学分级≥G2、≥G3、≥G4分别被定义为显著炎症、严重炎症和进展期炎症,病理学分期≥S2、≥S3和≥S4分别被定义为显著纤维化、严重纤维化和进展期纤维化.结果 HBeAg阳性患者血清HBsAg在G1与G3、G2与G3、S1与S4、S2与S4、S3与S4之间的差异均有统计学意义（P均＜0.05）,血清HBV DNA载量在S1与S4、S2与S4、S3与S4之间的差异均有统计学意义（P均＜0.05）;HBeAg阴性患者血清HBsAg在肝组织不同病理学分级和分期之间的差异无统计学意义（P＞0.05）,血清HBV DNA载量在G1与G3、S1与S2、S1与S3、S1与S4之间的差异均有统计学意义（P均＜0.05）.HBeAg阳性患者血清HBsAg诊断严重炎症和进展期纤维化的ROC曲线下面积分别为0.711 （95％ CI：0.647～0.775）和0.765（95％ CI：0.707～0.823）,血清HBV DNA诊断严重炎症和进展期纤维化的ROC曲线下面积分别为0.589（95％ CI：0.519 ～0.659）和0.700（95％ CI：0.632 ～0.769）;HBeAg阴性患者血清HBV DNA诊断非显著炎症和非显著纤维化的ROC曲线下面积分别为0.644（95％ CI：0.565 ～0.723）和0.684（95％ CI：0.606～0.761）.结论 血清HBsAg对HBeAg阳性患者肝组织严重炎症和进展期纤维化有一定的预测价值;血清HBV DNA对HBeAg阳性患者肝组织严重炎症和进展期纤维化和对HBeAg阴性患者肝组织非显著炎症和非显著纤维化有一定的预测价值.     

172例慢性乙型肝炎患者肝脏病理与血清HBV DNA水平的关系

目的:探讨慢性乙型肝炎(CHB)肝脏病理与血清HBV DNA水平的关系.方法:172例慢性乙型肝炎患者根据血清免疫学指标分为HBeAg阳性组和HBeAg阴性组,均进行肝穿刺组织学检查及采用实时荧光定量PCR法检测HBV DNA.结果:不论HBeAg阳性还是HBeAg阴性CHB患者炎症分级从G0到G4分为5级,结果显示各级患者HBV DNA含量比较差异无显著性意义(P＞0.05).CHB患者纤维化分期从S0到S4分为5期,结果显示各期之间HBV DNA含量比较差异无显著性意义(P＞0.05).结论:不论HBeAg阳性还是HBeAg阴性CHB患者,肝脏病理分级分期与血清HBV DNA水平无明显相关性.     

HBeAg阳性和阴性慢性乙型肝炎患者肝组织学与血清学关系的比较

目的 研究慢性乙型肝炎(CHB)患者(1×ULN≤ALT≤2×ULN)肝组织学与血清学的关系.方法 对全国多中心516例CHB患者(1×ULN≤ALT≤2×ULN)行血清学及肝穿刺病理检查,依据血清HBeAg表达水平将患者分为HBeAg阳性组和HBeAg阴性组,分析两组肝组织病理学与血清学指标的相关性.结果 HBeAg阳性患者肝组织炎症分级和肝纤维化分期与血清HBsAg和HBeAg表达水平呈负相关(P＜0.01),与血清透明质酸(HA)和α2-巨球蛋白水平呈正相关(P＜0.01),与血清HBVDNA水平无明显相关性;HBeAg阴性患者肝组织炎症分级和肝纤维化分期与血清HBV DNA水平呈正相关(P＜0.01),与HBsAg、HA和α2-巨球蛋白等无明显相关性.结论 血清HBV DNA可做为HBeAg阴性CHB患者肝脏病变程度的有效预测指标,HBsAg、HBeAg、HA和α2-巨球蛋白均可做为HBeAg阳性CHB患者肝组织损伤的预测指标.     

HBeAg阳性和阴性的慢性乙型肝炎患者组织病理学及免疫组化学研究

目的探讨HBeAg阴性和阳性慢性乙型肝炎（CHB）患者组织病理学及免疫组化学的特点。方法对156例HBeAg阴性和阳性CHB患者肝组织炎症分级（G）及纤维化分期（S）的结果进行对比分析,并分别探讨两组CHB患者HBVDNA与ALT、G及S的关系,检测CHB患者肝组织HBsAg和HBcAg阳性表达率。结果HBeAg阴性CHB患者HBVDNA含量明显低于HBeAg阳性者,肝组织炎症程度高于后者,HBVDNA水平与ALT、G和S呈正相关,HBeAg阳性CHB血清HBVDNA与ALT、G无相关性。CHB患者肝组织HBcAg阳性率随炎症程度升高而升高。结论与HBeAg阳性CHB相比,HBeAg阴性者HBVDNA水平低,炎症程度高,HBVDNA水平与ALT、G、S正相关。CHB患者肝组织HBcAg阳性率随炎症程度增高而升高。     

388例慢性HBV感染者血清学与肝组织病理学指标的相关性分析

分析388例慢性HBV感染血清学及肝组织病理学指标的相关性.结果发现,HBeAg阳性者肝组织炎症分级为G2、G3-G4及纤维化分级为S2、S3～s4所占比率较阴性者低;纤维化分级为SO、炎症分级为GO～G1者的HBV-DNA均值显著高于纤维化分级S1～S4、炎症分级G2～G4者(P＜0.05、0.01);肝组织HBsAg表达为"+"者与"++～+++"者的血清HBV-DNA均值无显著差异;肝组织HBcAg阳性者HBV-DNA均值显著高于阴性者(P＜0.01);血清ALT水平正常及轻度升高者肝组织纤维化和(或)明显炎症发生率显著低于ALT中、重度升高者(P＜0.05).认为血清HBV-DNA与肝组织HBcAg表达有一致性,与肝内HbsAg表达无明显相关,HBV.DNA水平低可能提示肝组织炎症活动度和纤维化程度高;对慢性乙肝病毒携带者行肝活检可判断肝组织病变程度并决定是否行抗病毒治疗.     

慢性乙型肝炎患者血清HBV DNA载量与肝组织病理学变化关系研究

探讨慢性乙型肝炎轻度患者血清HBV DNA载量与肝组织病理学变化的关系。方法根据血清HBeAg状态将310例慢性乙型肝炎轻度患者分为HBeAg阳性和HBeAg阴性,应用荧光定量PCR技术检测血清HBV DNA水平,常规进行肝活检术和病理学观察,分析血清HBV DNA载量与肝组织病理学变化的关系。结果224例HBeAg阳性患者肝组织炎症程度以G0（42.0%）为主,纤维化程度以S0（58.0%）为主;86例HBeAg阴性患者炎症程度以G0（29.1%）、G1（30.2%）、G2（34.9%）为主,纤维化程度以S0（51.2%）为主;HBeAg阳性患者血清HBV DNA水平与肝组织炎症程度无明显相关（r=-0.098,P＞0.05）,与纤维化分期间存在负相关关系（r=-0.309,P＜0.01）;HBeAg阴性患者血清HBV DNA水平与肝组织炎症程度存在正相关关系（r=0.306,P＜0.01）,与纤维化程度无明显相关（r=0.112,P＞0.05）。结论 HBeAg阳性与HBeAg阴性患者血清HBV DNA载量与肝组织病理学变化的关系存在显著差别,应区别分析其临床意义。     

慢性乙型肝炎患者临床和肝组织病理学特点及影响肝纤维化因素分析*

目的 分析HBeAg阴性与阳性慢性乙型肝炎（CHB）患者临床和肝组织病理学特点,探讨影响CHB患者发生明显肝纤维化的危险因素。方法 回顾性分析250例CHB患者血清HBV DNA水平、Fibroscan检测肝脏硬度（stiffness）值和肝穿刺组织病理学特点,应用多因素Logistic回归模型分析影响CHB患者发生明显肝纤维化的独立危险因素。结果 160例HBeAg阴性患者血清HBV DNA ≥1×10⁵ copies/ml者所占比例显著低于HBeAg阳性组（66.9%对99.4%,P<0.05）;HBeAg阴性组血清ALT和AST水平显著低于HBeAg阳性组（P<0.05）;血清HBeAg阴性组与阳性组肝组织炎症分级和纤维化分期总体分布差异无统计学意义（P>0.05）;多因素Logistic回归分析结果显示年龄≥40岁、HBV DNA水平高、PTA低和Stiffness水平高为CHB患者存在明显肝纤维化的独立危险因素。结论 血清HBeAg阴性与阳性CHB患者存在一些临床和肝组织病理学特征的差异,血清HBeAg阴性患者可能存在更为严重的临床和预后问题,需要给予特别的关注和管理。     

学龄前HBeAg阴性慢性乙型肝炎患儿临床特点分析

目的 探讨学龄前乙型肝炎e抗原(HBeAg)阴性慢性乙型肝炎患儿临床特点。方法 回顾性分析我院2018年5月—2019年5月收治的115例学龄前慢性乙型肝炎患儿的临床资料。依据HBeAg检查结果分为观察组(HBeAg阴性,n=46)与对照组(HBeAg阳性,n=69例)。对比两组基础资料、实验室检查结果[性别、年龄、病程、家族史、谷丙转氨酶(ALT)、谷草转氨酶(AST)、慢性乙型肝炎病毒(HBV DNA)]及肝组织炎症活动分级、肝纤维化分期。结果观察组性别、年龄、家族史、ALT、AST与对照组对比无显著差异(P0.05);观察组病程显著长于对照组,HBV DNA水平显著低于对照组,差异有统计学意义(P0.05)。观察组肝组织炎症活动分级以G3、G4级为主,对照组肝组织炎症活动分级以G1、G2级为主,组间对比差异有统计学意义(P0.05)。观察组肝纤维化分期以S3、S4期为主,对照组肝纤维化分期以S0、S1、S2期为主,组间对比差异有统计学意义(P0.05)。结论 学龄前HBeAg阴性慢性乙型肝炎患儿具有病程长、HBV DNA水平低的特点,且HBeAg阴性患儿更容易出现肝纤维化和病情持续恶化。     

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.     

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.     

N-acetyl-L-cysteine combined with mesalamine in the treatment of ulcerative colitis： Randomized,placebo-controlled pilot study

AIM： To evaluate the effectiveness and safety of oral N-acetyl-L-cysteine （NAC） co-administration with mesalamine in ulcerative colitis （UC） patients.
METHODS： Thirty seven patients with mild to moderate UC were randomized to receive a four-wk course of oral mesalamine （2.4 g/d） plus N-acetyl-L-cysteine （0.8 g/d） （group A） or mesalamine plus placebo （group B）. Patients were monitored using the Modified Truelove-Witts Severity Index （MTWSI）. The primary endpoint was clinical remission （MTWSI ≤ 2） at 4 wk. Secondary endpoints were clinical response （defined as a reduction from baseline in the MTWSI of ≥ 2 points） and drug safety. The serum TNF-α, interleukin-6, interleukin-8 and MCP-1 were evaluated at baseline and at 4 wk of treatment. RESULTS： Analysis per-protocol criteria showed clinical remission rates of 63% and 50% after 4 wk treatment with mesalamine plus N-acetyl-L-cysteine （group A） and mesalamine plus placebo （group B） respectively （OR = 1.71; 95% CI： 0.46 to 6.36; P = 0.19; NNT = 7.7）. Analysis of variance （ANOVA） of data indicated a significant reduction of MTWSI in group A （P = 0.046） with respect to basal condition without significant changes in the group B （P = 0.735） during treatment. Clinical responses were 66% （group A） vs 44% （group B） after 4 wk of treatment （OR = 2.5; 95% CI： 0.64 to 9.65; P = 0.11; NNT = 4.5）. Clinical improvement in group A correlated with a decrease of IL-8 and MCP-1. Rates of adverse events did not differ significantly between both groups.
CONCLUSION： In group A （oral NAC combined with mesalamine） contrarily to group B （mesalamine alone）, the clinical improvement correlates with a decrease of chemokines such as MCP-1 and IL-8. NAC addition not produced any side effects.     

Delorme's transrectal excision for internal rectal prolapse

Surgical therapy of functional outlet obstruction in patients with internal rectal intussusception may include abdominal, perineal, or transrectal procedures. Because abdominal procedures often result in significant physiologic impact but unrelieved constipation, the authors have elected Delorme's transrectal excision for management of these patients. Since a short-term placebo effect attends many therapies, this report describes results of transrectal excision only after a threeyear postoperative period. Delorme's transrectal excision of internal intussusception accomplished sustained symptomatic relief in over 70 percent of otherwise refractory constipated patients. The association of internal intussusception with other abnormalities underscores the importance of defining both anatomic and functional components when selecting patients whose constipation may require surgical therapy. Critical technical elements, surgical pitfalls, and potential complications of the procedure are discussed.Poster presentation at the meeting of The American Society of Colon and Rectal Surgeons, Toronto, Canada, June 11 to 16, 1989.     

The oral glucose tolerance test: A comparison of the time points on the basis of limit values,normal dispersion,and reproducibility

Summary Time points in the glucose tolerance test (GTT) are compared on the basis of limit values, dispersion within a reference population, and reproducibility. We suggest using the distance between a limit value and the median reference value as a measure of the magnitude of abnormality. The distance between 140 mg/100 ml and the median fasting plasma glucose value is chosen as a standard distance and limits for other points in the GTT are calculated to equal this standard distance of abnormality. We suggest that the probability of correctly interpreting an inividual result is directly related to the reproducibility of the test and inversely related to the percentage of the total range of values which is dispersed among the normal population. The ratio of reproducibility to percentage normal dispersion is proposed as an index of the probability of correctly interpreting an individual result. According to this index, the probability of correct interpretation varies in order: fasting plasma glucose concentration>3-h>2-h>0.5-h>1-h plasma glucose concentration.