Bax、Bcl—xL、Bcl-2蛋白表达与慢性丙型肝炎炎症纤维化分级分期的关系

采用免疫组化法评估了89例慢性丙型肝炎病人肝组织活检标本中Bax、Bcl—xL、Bcl-2蛋白的表达水平。结果，参照Scheuer评分标准，肝细胞Bax蛋白的表达水平与炎症分级（P〈0．001）和纤维化分期（P=0．011）呈显著负相关。虽然肝细胞Bcl—xL蛋白的表达水平在G3和S4时最高，但与炎症分级（P=0．106）和纤维化分期（P=0．078）无显著相关性。[第一段]     

慢性乙肝患者肝细胞胞浆和胞核的HBcAg表达强度与肝脏炎症纤维化、乙肝病毒复制的关系

目的 分别评定慢性乙型肝炎(Chronic hepatitis B,CHB)患者肝细胞胞浆和胞核的HBcAg表达强度,分析与临床的关系,研究肝细胞胞浆和胞核内HBcAg的作用。方法 对CHB患者肝活检标本317例行免疫组化染色,显示HBc Ag在肝细胞胞浆和胞核的表达强度,同时记录患者的多种临床指标。分别分析肝细胞胞浆和胞核的HBcAg表达强度相互关系以及与各临床指标的关系。结果 HBcAg胞浆和胞核表达强度无相关关系(r=0. 104,P=0. 064)。HBcAg表达胞核阴性组比阳性组呈现年龄更大,ALT、肝组织炎症活动度分级(G)及纤维化分期(S)更高,但血清HBeAg阳性率更低的特点; HBcAg表达胞浆阴性和阳性组两组的上述指标差异均无统计学意义(P>0. 05)。HBcAg胞核和胞浆表达阴性组均比阳性组血清HBVDNA载量更低,差异有统计学意义(P=0. 025,P=0. 00)。结论 肝细胞胞核的HBcAg表达强度与肝脏炎症和纤维化联系的紧密性远高于肝细胞胞浆内HBcAg。肝细胞胞核内HBc Ag表达强度可能才是肝脏炎症活跃和纤维化进展的关键,且CHB患者肝细胞胞浆、胞核的HBcAg表达强度均与HBV复制呈正相关。     

慢性乙型肝炎免疫耐受期患者肝穿组织的临床病理学特征

目的：总结慢性乙型肝炎免疫耐受期患者的临床病理学特征。方法：收集符合慢性乙型肝炎免疫耐受期临床诊断并行肝组织穿刺活检的病例共84例,血清学检测其乙肝病毒（HBV）标志物、HBVDNA病毒载量及丙氨酸氨基转移酶（ALT）、天冬氨酸氨基转移酶（AST）水平。所有标本均行HE染色、Masson、网状纤维、D—PAS特殊染色以及乙型肝炎表面抗原（HBsAg）、乙型肝炎核心抗原（HBcAg）免疫组化染色,观察并评价肝组织的炎症活动度、纤维化程度及HBsAg和HBcAg分布及表达模式。结果：84例患者中男：女=2：1,发病年龄0～35（19．01±7．54）岁;57．14％的患者有明确家族史;HBVDNA载量10^7～10^10copies／ml;炎症活动度及纤维化分期处于G抵者最多（51／84,60．71％）,最少的为G1/S2和G2/S2,分别各占2．38％（2／84）;不同炎症活动度及不同纤维化程度之间HBVDNA载量无明显差异（P〉0．05）;毛玻璃样肝细胞量与HBsAg表达量呈明显正相关（r=0．472,P=0．001）,与HBcAg表达量无相关性（r=-0．005,P=0．973）;肝组织内HBcAg的表达量较HBsAg多,且差异有高度统计学意义（P〈0．01）,HBcAg的表达以核型为主。结论：慢性乙型肝炎免疫耐受期患者病毒复制力强。虽然炎症及纤维化均呈静止状态,但仍有轻度的炎症及纤维化存在,应密切随访。警惕其进展。     

322例慢性乙型肝炎患者肝脏病理与病毒学指标的相关性研究

目的 研究慢性乙型肝炎患者肝脏病理与肝组织中及血清病毒标志物等因素的相关性。方法 回顾322例HBsAg阳性超过6个月并行肝穿刺活组织检查患者的临床资料,分析肝脏病理与肝组织中病毒标志物、血清HBeAg状态、血清HBV DNA水平及血清丙氨酸氨基转移酶（alanine aminotransferase,ALT）水平的相关性。结果 322例患者中,肝组织炎症分级（G）＞1且纤维化分期（S）＞1者314例,G≥3者44例,S≥3者40例。G与S呈明显正相关 (r=0.594,P<0.05)。 肝组织HBsAg、HBcAg不同表达状态患者,不同血清HBeAg状态患者,不同血清HBV DNA水平患者的肝脏炎症分级及其肝脏纤维化分期比较,差异均无统计学意义（P>0.05）。不同血清ALT水平患者的肝脏炎症分级比较,差异具有统计学意义（P<0.05）,血清ALT水平与肝脏炎症分级呈正相关（r=0.322,P<0.05）,而与肝脏纤维化分期的相关性无统计学意义(r=0.267,P>0.05)。结论 慢性乙型肝炎患者的肝脏炎症及纤维化程度与肝组织中病毒标志物、血清HBeAg状态、血清HBV DNA水平并无明显相关性,其炎症分级与血清ALT水平呈明显正相关。     

脑星形细胞瘤组织中VEGF、iNOS蛋白的表达及其意义

目的探讨血管内皮生长因子（VEGF）、诱导性一氧化氮合成酶（iNOS）蛋白在脑星形细胞瘤中的表达及其意义。方法采用SP免疫组织化学法，检测VEGF、iNOS蛋白在59例不同病理分级脑星形细胞瘤组织中的表达情况。结果VEGF、iNOS蛋白表达的阳性率分别为76.2％（45／59）、71.2％（42／59），VEGF与病理分级密切相关（P〈0．05）；VEGF、iNOS均与肿瘤单位视野中血管平均值（MVD）密切相关（P〈0．05）。VEGF、iNOS的表达存在相关性。结论VEGF表达与脑星形细胞瘤的发生发展及肿瘤性血管的生成存在密切的相关性；iNOS通过协同和促进VEGF的表达及肿瘤性血管的生成，间接参与肿瘤细胞的恶性演化。     

慢性乙型肝炎肝组织HBsAg和HBcAg的表达

目的探讨慢性乙型肝炎患者肝组织中HBsAg和HBcAg的表达与血清HBV-DNA含量、肝组织中HBV-DNA含量、肝组织病理及临床之间的关系。方法选择慢性乙肝患者83例,检测血清HBV-DNA的含量,并行肝穿刺取肝组织,用免疫组化法检测乙肝患者肝组织中HBsAg和HBcAg的表达并检测肝组织中HBV-DNA的含量,同时行常规肝组织病理染色。结果在慢性乙型肝炎患者肝组织内HBsAg和HBcAg阳性表达率分别为81.9%和53%。HBsAg 98.5%是浆膜型;HBcAg浆膜型占62.8%、胞核型占37.2%,浆膜型的肝组织炎症、纤维化较胞核型明显。HBsAg表达强度与血清HBV-DNA定量、肝组织HBV-DNA定量及肝组织炎症和纤维化之间均无相关性。HBcAg表达强度随着血清HBV-DNA定量的增加而增加,呈正向关联（r=0.291,P=0.008）,与肝组织HBV-DNA定量呈现明显的正向关联（r=0.664,P〈0.001）,与肝组织炎症、纤维化分级也呈正相关（r=0.611,0.841,P〈0.001）。结论慢性乙肝患者肝组织免疫损伤发生的免疫应答的主要抗原是HBcAg。将肝组织中HBcAg的表达结合HBV-DNA载量作为抗病毒治疗指标更可靠。     

乳腺癌组织褪黑素受体1和雌激素受体表达的相关性及其临床意义

目的：探讨褪黑素受体1（MT1）和雌激素受体（ER）在乳腺癌组织中表达水平的相关性及其临床意义。方法: 采用免疫组化染色（SP）法检测90例乳腺浸润性导管癌、34例乳腺导管内癌和35例癌旁乳腺组织中MT1和ER的表达水平,并对其表达进行相关性分析。结果: ER、MT1在两组乳腺癌中的阳性表达率均高于其在癌旁乳腺组织中的阳性表达率,差异有统计学意义（P＜0.05）。在124例乳腺癌中,ER与MT1的表达均与组织学分级（P=0.036,P=0.015）、临床分期（P=0.014,P=0.021）及淋巴结转移（P=0.014,P=0.006）有相关性,差异有统计学意义。MT1与ER在乳腺浸润性导管癌、乳腺导管内癌组织中的表达呈负相关（r=-0.411,P=0.000;r=-0.454, P=0.007）。结论： MT1高表达和ER低表达与乳腺癌的发展和转归有关,联合检测MT1、ER的表达可为乳腺癌预后的判断及靶向治疗提供实验依据。     

干细胞表面标志物CD133在肝癌组织中的表达及其临床意义

目的：研究干细胞表面标志物CDl33在肝癌组织中的表达及其与临床特征的关系，并探讨与预后的相关性．方法：用免疫组织化学Envision两步法检测52例肝细胞癌组织中CD133及Ki-67的表达，对照组6例为正常肝组织．对临床病理学指标和术后生存率进行比较分析．结果：52例肝癌组织中CD133表达的平均染色强度为1．07±0．32．按照Edmondson病理分级：Ⅰ-Ⅱ级肝癌组织的CD133平均染色强度为0．67±0．18，Ⅲ～Ⅳ级为1．17±0．24，2组间差异有统计学意义（F=62．96，P〈0．05）．TNM临床Ⅰ～Ⅱ期肝癌组织中CD133的平均染色强度为0．71±0．20，Ⅲ～Ⅳ期为1．19-t-O．29，2组间差异有统计学意义（F=57．13，P〈0．05），但CD133的表达与患者年龄、性别、肿瘤的大小无关．Ki-67在肝癌组织阳性表达率为57．7％，Ki-67的表达与肝癌的分化和临床分期相关（F=8．56，7．45，P〈0．05）；CD133与Ki-67的表达呈正相关（F=18．37，P〈0．05）；CD133阴性患者平均生存率较阳性患者显著延长（P〈0．05）．结论：CD133可能与肝癌的发生、发展相关，有望成为判断患者预后的指标之一．     

膀胱移行细胞癌iNOS的表达及其与MVD关系的研究

目的：探讨膀胱移行细胞癌组织中诱导型一氧化氮合酶（iNOS）的表达及其与肿瘤微血管密度（MVD）的关系。方法：采用iNOS及CD34抗体对35例膀胱移行细胞癌标本，12例癌旁粘膜标本及8例正常膀胱粘膜标本进行免疫组化染色，观察标本中iNOS的表达及与MVD值之间的相关性。结果：35例肿瘤标本中iNOS阳性表达率85．7％，iNOS表达与肿瘤病理分级、分期无关。移行细胞癌MVD值较癌旁粘膜、正常粘膜高，且低分化肿瘤的MVD值较高分化者高，浸润性肿瘤的MVD值较浅表性肿瘤高；iNOS表达与MVD存在正相关性。癌旁粘膜与正常膀胱粘膜比较，iNOS表达与MVD值的差别无 显著性意义。结论：iNOS在膀胱移行细胞癌中的表达增高，可能与肿瘤血管形成有关。     

肝内血管病变及血管内皮生长因子与乙型炎关系的病理学研究

目的：研究肝内血管病变及血管内皮生长因子（VEGF）与乙型肝炎（乙肝）的关系。方法：选取300例乙肝患者（急性乙肝，慢性乙肝G1－G4及肝硬变患者各50例）肝活检组织及52只SD大鼠（CCl4诱导模型组40只及正常对照组12只）不同时间（2，5，8，12周）肝组织，采用：（1）动物实验；（2）肝活检随访观察及体视学分析技术；（3）组织化学（组化）染色：对肝组织中胶原，网状及弹力纤维进行染色；（4）免疫组织化学（免疫组化）染色；用纤维连接蛋白（FN），层连蛋白（LN），IV－型胶原（Ⅳ－Co)，平滑肌肌动蛋白（α－SMA）及VEGF等单克隆抗体对肝组织进行染色；（5）酶联免疫吸附法（ELISA）定量检测：定量检测75例乙肝患者血清中VEGF含量。结果：（1）CCl4大鼠实验中，在实验不同时间内，其组织肝内血管病变，肝组织病变及VEGF的表达各不相同，早，中期（2－5周），肝组织炎症反应显著，中央静脉周围肝细胞脂肪变，VEGF阳性肝细胞主要分布在脂肪变区域；晚期（8－12周）则肝组织炎症反应轻微，但肝细胞病变显著，血管破坏，血管及成肌纤维细胞增生更趋明显，并见有局部纤维瘢痕形成，假小叶内肝组织肝窦扩张或毛细血管化，其VEGF示阳性；（2）乙肝肝细胞的变性坏死等与肝内血管病变导致的肝血供障碍密切相关，肝内血管病变主要有血管炎症，血管塞，血管破坏，血管增生及肝窦狭窄，阻塞，扩张和肝窦毛细血管化，其贯穿于乙肝的整个病程中并发挥着非常重要的作用。（3）乙肝肝组织中VEGF的表达及血清中VEGF含量变化与其肝炎分级（G），分期（S）及血管病变关系密切，在急性乙肝，VEGF呈弥漫性强阳性表达，血清VEGF含量显著升高（P＜0．001），在慢性乙肝及肝硬变（LC），其血清VEGF含量并无升高，到LC反而下降（P＜0．01），肝组织中VEGF散在表达，以扩张肝窦的内皮细胞及周围肝细胞较显著，其表达在血管形成前期最明显，而在肝血管生成期则逐渐降低。结论。肝内血管病变在乙肝的整个病程中发挥着非常重要的作用；VEGF与乙肝肝细胞的再生及肝病主的程度有关，在肝内血管增生及改建中担当一最重要的角色，其在肝组织中内增强表达发生于乙肝病变的始发阶段。     

Value of D-Dimers in patients with acute aortic dissection

Objective: To evaluatel the value of D-dimers in patients with acute aortic dissection (AAD). Methods: This study consisted of 16 patients with AAD and 27 non-AAD patients. Serum D-dimets were measured by Sta-Liatest D-DI immunoturbidimetric assay. Results: D-dimer level was higher (P ＜ 0.001) in patients with AAD(7.91 ± 5.52 μg/ml) than that in non- AAD group(1.57±1.24 μg/ml). D-dimer was positive (＞0.4 μg/ml) in all patients with AAD and in 10 control group patients (37%). Among patients with acute AAD, D-dimers tended to be higher in Stanford A than in Stanford B (8.67 ± 4.31 μg/ml vs. 3.24±1.27 μg/ml, P ＜0.01). D-dimer values tended to be higher in more extended disease(3.84 ± 1.65 μg/ml, 8.57 ± 3.58 μg/ml and 11.87 ± 5.69 μg/ml in thoracic aorta, thoracic and abdominal aorta, thoracic and abdominal aorta and iliacal arteries, respectively, P ＜ 0.05 for both 8.57 ± 3.58 and 11.87 ± 5.69 vs. 3.84 ± 1.65 ). Including the control group into the analysis, we found a sensitivity of 100%, a negative predictive value of 100%, and a specificity of 66% and a positive predictive value of 64% for D-dimer in diagnosis of AAD in our patients with suspected AAD. Conclusion: D-dimer was elevated in patients with AAD. A negative D-dimer test result could be useful in excluding AAD.     

Research of combined liver-kidney transplantation model in rats

Objective： To set up a simple and reliable rat model of combined liver-kidney transplantation. Methods： SD rats served as both donors and recipients. 4℃ sodium lactate Ringer＇s was infused from portal veins to donated livers,and from abdominal aorta to donated kidneys, respectively. Anastomosis of the portal vein and the inferior vena cava （IVC） inferior to the right kidney between the graft and the recipient was performed by a double cuff method, then the superior hepatic vena cava with suture. A patch of donated renal artery was anastomosed to the recipient abdominal aorta. The urethra and bile duct were reconstructed with a simple inside bracket. Results： Among 65 cases of combined liver-kidney transplantation, the success rate in the late 40 cases was 77.5%. The function of the grafted liver and kidney remained normal. Conclusion： This rat model of combined liver-kidney transplantation can be established in common laboratory conditions with high success rate and meet the needs of renal transplantation experiment.     

BLOOD PRESSURE CHANGE WITH AGE IN SALT-SENSITIVE TEENAGERS

Objective To observe blood pressure change with age in salt-sensitive teenagers whose salt sensitivity were determined by repeated testing.Methods Salt sensitivity was determined through intravenous infusion of normal saline combined with volume-depletion by oral diuretic furosemide in 55 teenagers. After five years, salt sensitivity was re-examined and subject blood pressure was followed up. Blood pressure changes in salt-sensitive teenagers were compared to that of non-salt sensitive teenagers over five years.Results After 5 years, the repetition rate of salt sensitivity determined by intravenous saline loading is 92.7%. In teenagers with salt sensitivity on the baseline, both the systolic blood pressure increments and increment rates were much higher than non-salt sensitive teenagers (12.7±12.1 mmHg vs. 2.8±5.2 mmHg, P＜ 0.01; 12.2%± 12.0% vs. 2.5% ±4.4%, P＜ 0.001,respectively). There was a similar trend for diastolic blood pressure (8.4 ± 6.4 mmHg vs. 3.7 ± 6.4 mmHg, P = 0.052; 13.2% ±10.6 % vs. 6.8%± 10.1%, P = 0.053, respectively).Conclusions Salt sensitivity determined by intravenous saline loading showed good reproducibility. Blood pressure increments with age were much higher in salt-sensitive teenagers than non-salt sensitive teenagers, especially in terms of systolic blood pressure.     

安心颗粒对急诊经皮冠状动脉介入术后生活质量影响的研究

目的：评价使用安心颗粒对急诊经皮冠状动脉介入术（PPCI）术后生活质量的影响.方法：将160例接受PPCI的急性ST段抬高型心肌梗死患者随机分为安心颗粒组（术前顿服安心颗粒8.8g,术后安心颗粒4.4 g/次,每日2次）和对照组（仅接受基础药物治疗）.所有患者均服用阿司匹林、氯吡格雷和阿托伐他汀.分别在入院时、出院前1d、出院后180 d时,应用心肌梗死多维度量表（MIDAS）、中文版SF-36评价量表对患者生活质量评分.并观察术后30 d以内的出血并发症、血小板减少症发生情况.结果：入院时和出院前1d,两组患者的心肌梗死MIDAS、SF-36量表评分比较无差异（P＞0.05）;出院后180 d时,与对照组比较,安心颗粒组MIDAS、SF-36评分明显减低（P＜0.05）;组内与入院时比较,两组出院前1d、出院后180 d时,MIDAS、SF-36评分均降低（P＜0.05）.两组患者在随访期间均无大量出血、少量出血、重度和极重度血小板减少症发生,安心颗粒组有4例、对照组有7例发生不明显出血（P＞0.05）.两组发生轻度血小板减少症的患者数比较无差异（P＞0.05）.结论：PPCI使用安心颗粒,能改善急性ST段抬高型心肌梗死患者的生活质量,且不增加出血风险.     

The comparative studies of the influences of Urapidil and Nicardipine on sino-atrial node function, atrio-ventricular node function and hemodynamics

Objective:To investigate the influences of urapidil and nicardipine on rabbit sinus function,atrio-ventricular node function and hemodynamics.Methods:Thirty-two Angora's rabbits were selected and randomly divided into four groups.U1 group:urapidil 0.25 mg/kg;U2 group:urapidil 0.5 mg/kg;N1 group:nicardipine 10 μg/kg;N2 group:nicardipine 20 μg/kg.All these medicine were administrated within 30 seconds.Measurements were taken before and after the administration of urapidil or nicardipine for the following data:mean blood pressure(MAP),heart rate(HR),sino-atrial conduction time(SACT),maximal sinoatrial recovery time(SNRTmax)corrected sinus node recovery time(CSNRT),index of sinus node recovery time(SNRTI),Wenckebach A-V conduction frequency (WB),and P-R interval.Results:Significant MAP and HR changes were identified in all of the four groups before and after administration of both urapidil and nicardipine.No significant changes could be found in the rest of the parameters.Intergroup analysis showed that SACT and CSNRT of N1 and N2 groups were shorter than those of the U2 group(P＜0.01);the MAP decreased(P＜0.01)and the HR increased drastically(P＜0.01).Conclusions:Neither urapidil(0.25 mg/kg,0.5 mg/kg)nor nicardipine(10μg/kg,20μg/kg)has any significant influence on rabbit sinus function or rabbit atrio-ventricular node function.Nicardipine could be a better choice than urapidil for parafunctional sinus node patients.     

Dynamic Changes in Serum Estradiol and Progesterone levels in Patients of Premenstrual Syndrome with Adverse Flow of Liver-qi

Objective:To probe into the influence of changes of ovarian hormones on the pathogenesis of the specific sub-type premenstrual syndrome(PMS)and reveal partial microcosmic mechanisms of adverse flow of liver-qi.Methods:Estradiol(E2)and progesterone(P)levels in serum were determined at different phases of menstrual cycle by radioimmunoassay.Results:In the group of PMS with adverse flow of liver-qi.the secretive peak value Of E2 and P at the follicular phase significantly decreased,and the secretive peak value at the luteal phase did not come into being.Conclusions:Low E2 and P secretive peak at the follicular phase and absence of secretive peak at the luteal phase is one of the microcosmic mechanisms of PMS with adverse flow of liver-qi.One of the pathophysiologic mechanisms of specific sub-type PMS is probably the continuous low level of E2and P.     

Real-time Three-dimensional Echocardiography in Assessment of Left Ventricular and Right Ventricular Volumes

Real-time three-dimensional echocardiography (RT3DE)is a new ultrasound technique that enables dynamic threedimensional visualization and quantification of the heart in real time. Investigation of feasibility and methodology of RT3DE in determining left ventricular (LV) and right ventricular (RV) volumes, RT3DE was performed in 35 normal adults using Philips SONOS 7500 system with a 2-4 MHz matrix array transducer. The 60°×60° "pyramid" volume database was obtained and analyzed on a TomTec echo workstation. Both LV and RV volumes were calculated with four 3DE methods (i.e. apical 2, 4, 8, and 16-plane) through manually tracing ventricular endocardial borders in end diastole and end systole. Stroke volumes were then calculated. LV volume was also measured by 2DE Simpson's rule using GE VIVID 7 ultrasound machine.     

SCREENING FOR A 21-CHROMOSOME ABNORMALITY IN PREIMPLANTED EMBRYOS OF ELDERLY WOMEN

Increasing maternal age is the only etiological factor unequivocally linked to Down's syndrome in humans. The occurrence rate of newborns with Down's syndrome is about 1/220 in women over 35 years old. However, the occurrence rate in embryos fertilized in vitro, of the elder woman is unclear. Using FISH we screened the number of chromosome 21 in preimplanted embryos of 5 elderly women (average age, 38.4 years) to study the feasibility and necessity of screening trisomy 21 in embryos in patients over 35 years old at the in vitro fertilization (IVF) center.     

Scientific principles and rigorous processes should be followed in developing clinical guidelines for therapeutic interventions of integrative medicine

A clinical guideline for the therapeutic interventions of integrative medicine may be defined as a written document which states a series of recommendations on therapeutic interventions of integrative medicine for a special disease or condition. The guideline may provide assistance to medical professionals in making clinical decisions aimed at improving the clinical outcome of patients and reducing the costs of medical care（~＇4~. Recommendations issued by a guideline should be based on the best available evidence in both Western and Chinese medicine. For fulfilling this purpose, the development of clinical guidelines for therapeutic interventions in the field of integrative medicine should follow scientific principles and undergo a rigorous processes.     

Expression of OPGmRNA and ODFmRNA in the patients of hip fracture due to osteoporosis

Objective：To investigate the gene expression of osteoprotegerin（OPG） and osteoclast differentiation factor（ODF） in the bone tissue of patients with hip fracture due to osteoporosis. Methods：OPGmRNA and ODFmRNA in the bone tissue in 50 cases of osteoporosis sufferers（over 50 years old） with hip fracture（Observer Group） and 30 cases of hip facture sufferers with no osteoporosis（Control group） were analyzed with the Semi-Quantitative RT-PCR method. Results：The mRNA expressed of ODF, OPG were both high in the patients with hip fracture. In the control group, the expression of OPG mRNA was observed, while the expression of ODF mRNA was very slight. Conclusion：Aged patients contained all signals including OPG, ODF that are essential for inducing osteoclastogenesis and promoting bone resorption.