先天性巨结肠肌间神经丛形态学观察及其意义

目的观察先天性巨结肠肌间神经丛形态学并分析其意义。方法对8例先天性巨结肠患者手术标本过行苏木素伊红(HE)染色和免疫组织化学S100蛋白染色,进行形态学观察。结果先天性巨结肠狭窄部肠壁肌间神经无神经细胞,可见增多的直径增粗无髓鞘纤维,呈波浪状弯曲。雪旺氏细胞增多,结肠扩张段肌间神经丛可见神经节细胞,神经纤维无明显增粗,数量无明显增多。结论先天性巨结肠肌间神经丛形态学明显异常改变,与无神经节细胞病变肠段结肠发育障碍有关。     

神经生长相关蛋白-43基因及其蛋白在先天性巨结肠肠组织中的表达

目的探索神经生长相关蛋白-43(GAP-43)在先天性巨结肠痉挛段和扩张段肠组织中的表达情况,进一步探索先天性巨结肠的发病机理。方法收集2012年1月至2013年6月期间因先天性巨结肠于深圳市儿童医院行巨结肠根治术的30例患儿的活体肠组织标本,行免疫组化染色及荧光定量聚合酶链反应(RT-PCR)以检测扩张段和狭窄段肠组织中GAP-43 m RNA及其蛋白的表达,并比较扩张段和狭窄段肠组织中两者表达的差异。结果RT-PCR结果显示,痉挛组肠组织中GAP-43 m RNA的表达水平的中位数为0.052 8,低于扩张组的0.119 0(P<0.05)。免疫组化染色结果显示:30例患儿的狭窄段肠组织和扩张段肠组织的肌间神经丛及黏膜下神经丛中GAP-43蛋白均呈阳性表达,但痉挛段黏膜下神经丛和肌间神经丛的染色均较扩张段相应部位浅;与扩张组的黏膜下神经丛和肌间神经丛比较,痉挛组相应部位的GAP-43蛋白的平均光密度值均较低(P<0.05)。结论先天性巨结肠狭窄段肠组织中GAP-43蛋白的表达较扩张段肠组织下调,提示GAP-43蛋白可能是先天性巨结肠发病的危险因素之一。     

Cajal间质细胞在先天性巨结肠分布的研究

目的：通过观察cajal间质细胞（interstitial cells of cajal，ICC）在正常结肠及先天性巨结肠先天性巨结肠（hirschsprung’s disease，HD）患者痉挛段、移行段、扩张段的分布，探讨HD的发病机制。方法：收集25例HD患儿标本，于术中分别选取扩张段、移行段、痉挛段肠壁的全层组织，另取6例手术患儿的正常结肠全层组织标本，常规固定石蜡包埋组织切片备用。对标本行c-Kit免疫组织化学染色。光镜观察ICC的分布，计数并进行统计学分析。结果：正常结肠ICC主要分布在环肌内侧面与黏膜下层之间即黏膜下ICC（submucosal ICC．ICC—SM）、环肌与纵肌之间的肌间神经从周围即肌间ICC（myenteric ICC，ICC—MY）以及环肌与纵肌内。HD患儿痉挛段ICC—SM、ICC—IM细胞数较扩张段和正常对照组明显减少（P〈0．01），且ICC的细胞突起的分支亦减少，彼此之间不能形成完整的细胞网络。而扩张段ICC与正常对照组比较无明显差异（P〉0．05）。结论：HD患儿结肠ICC的异常分布，可能是HD发病、肠管蠕动障碍以及排便异常的原因之一。     

层粘连蛋白在先天性巨结肠的表达及意义

目的：观察先天性巨结肠（HD）不同节段肠壁层粘连蛋白（LN）的表达，探讨LN与HD发病的关系。 方法：收集30例手术切除HD标本，分别行LN免疫组化研究和实时荧光定量PCR，观察其分布情况，并行统计学处理。 结果：LN染色面积及染色强度从狭窄段到正常段依次减弱，差异有统计学意义（P<0.05）；LN基因在狭窄段的表达是正常段的2.15倍，其表达水平狭窄段>移行段>正常段。 结论：HD中LN的分布出现异常，是HD发病的重要原因。     

先天性巨结肠不同节段肠壁神经、平滑肌的分布及临床意义

目的 观察先天性巨结肠(HD)不同节段肠壁神经和平滑肌的病变范围,探讨先天性巨结肠根治术后肠动力功能紊乱原因及手术切除结肠范围.方法 用免疫组织化学和苏木素-伊红(HE)染色法,检测20例先天性巨结肠肠壁神经节细胞、神经纤维和平滑肌细胞病理组织学改变及分布范围.结果 巨结肠不同节段肠壁神经节细胞、神经纤维数量及突触素(Syn)、神经节细胞黏附分子(NCAM)的阳性表达,在距扩张远端8 cm虽未达到正常,但与对照组差异减小(P＞0.05).环肌层和纵肌层出现不同程度增厚,在距扩张远端8 cm仍未正常(P＜0.01).肌层出现空泡样变,与对照组比较差异无统计学意义(P＞0.05).结论 先天性巨结肠切除段肠壁神经、平滑肌层均存在病变,在距扩张段的远端8 cm处,两者病变总体缓解.在允许情况下,手术切除结肠的范围应达到或超过此范围.     

慢传输型便秘结肠神经丝蛋白和S—100蛋白的表达及意义

目的：探索结肠慢传输型便秘的发病机制。方法：采用免疫组织化学方法研究３３例慢性传输型便秘的病人（ＳＴＣ组）和２５例非便秘性结肠（对照组）升、横、降及乙状结肠肌间神经丛内神经丝蛋白和Ｓ－１００蛋白的表达。并利用图像分析系统作定量分析。结果：ＳＴＣ组结肠ＨＥ染色显示肌间神经丛未见明显异常,免疫组织化学染色示,对照组各段肠壁肌间神经丛内神经丝蛋白和Ｓ－１００蛋白的含量较恒定（Ｐ〉０．０５）。ＳＴＣ组结肠各段与对照比较。神经丝蛋白的含量无明显减少（Ｐ〉０．０５）,但出现堆积聚集现象,平均光密度明显高于对照组（Ｐ〈０．０１）;Ｓ－１００蛋白的含量及平均光密度明显高于对照组（Ｐ〈０．０１）。且随着病程的延长而增加,二者呈直线相关（Ｐ〈０．０２）。结论：ＳＴＣ结肠肌间神经丛的病理改变是全结肠性改变。神经丝蛋白的堆积聚集和神经     

先天性巨结肠的外科治疗

先天性巨结肠（Hirschsprungdisease，HD）是以便秘为主要临床表现的一种常见的消化道畸形．病因为外胚层神经嵴细胞迁移发育过程停顿．病变肠壁肌间神经丛和黏膜下神经丛的神经节细胞缺如。使肠段失去正常蠕动（即间歇性收缩和松弛的推进式运动）而处于经常的痉挛状态，造成粪便排出障碍．近端肠管则被动继发扩张，异常扩大、肥厚，形成所谓的巨结肠。     

Cajal间质细胞在先天性巨结肠和巨结肠同源病结肠中的分布研究

目的研究先天性巨结肠（Hirschsprung’s disease，HD）和巨结肠同源病（allied Hirschsprung’s disease，AHD）肠壁内Cajal间质细胞（interstitial cells of Cajal，ICCs）的分布状态，探讨HD和AHD的发病机制。方法选择确诊为HD和AHD的患者各20例，取巨结肠根治术吻合口远端的全层肠壁作为实验组，另取16例正常结肠标本作为对照组。用鼠抗人c—kit单克隆抗体（CD117）标记ICCs，Image Pro-Plus图像分析系统检测ICCs。结果对照组中大量ICCs分布在肌间神经丛周围和环纵肌层内，ICCs包绕神经丛周围，肌层间ICCs连续分布；HD组远端肠管中肌层间和各肌层内ICCs明显减少甚至缺如，与对照组比较差异有统计学意义，P〈0．01；AHD组远端肠管中神经丛大小不一，ICCs分布差异大，大多数神经丛区ICCs减少，环肌层内ICCs明显减少，与AHD组和对照组比较差异有统计学意义，P〈0.01。HD组远端结肠中ICCs减少比AHD组显著，差异有统计学意义，P〈0．01。结论HD、AHD病变肠管中除了神经节细胞的异常外，同时存在ICCs异常；ICCs在HD和AHD的分布不同可能与两者临床症状差异有关；肠管中ICCs数量可能与临床症状及预后有一定关系。     

先天性巨结肠突触素免疫组织化学研究

目的:采用突触素免疫组织化学方法,对先天性巨结肠神经肌肉连接进行研究,并探讨其与先天性巨结肠发病的关系。方法:应用免疫组化技术对20例先天性巨结肠病变肠段及10例正常结肠组织标本行突触素神经肌肉连接标记,光镜下观察其免疫反应。结果:对照组的结肠突触素免疫反应呈强阳性表达,先天性巨结肠组扩张肠段突触素免疫反应呈阳性或弱阳性表达,狭窄段肠壁突触素免疫反应呈阴性表达。结论:先天性巨结肠病变肠段同时缺乏内源性神经支配和外源性神经支配,处于完全失神经支配状态,导致原神经节细胞病变肠管功能障碍。     

先天性巨结肠神经营养因子-3、酪氨酸激酶C的表达及其意义

目的　探讨神经营养因子(NT ) 3及其受体酪氨酸激酶(Trk)C在先天性巨结肠(HD)中的表达及其意义。方法　采用免疫组织化学方法检测3 2例HD患者不同节段肠组织中神经节细胞NT 3、TrkC的表达水平。结果　正常肠段肌间和黏膜下神经丛内神经节细胞呈NT 3、TrkC强阳性表达。HD狭窄段未见NT 3、TrkC阳性染色;移行段神经节细胞NT 3、TrkC阳性率(5 3 .1%、2 8.1% )均较扩张段(93 .8%、43 .8% )显著降低(P <0 .0 5 )。结论　NT 3及其受体TrkC在神经节细胞缺乏肠段的异常表达可能与HD的发病机制有关,对HD具有潜在诊断价值     

Glial fibrillary acidic protein and neurofilament protein in medulloblastoma

Medulloblastoma is the most common primitive neuroectodermal tumor (PNET) with the potential to differentiate along glial or neuronal lines. Thirty cases of medulloblastoma were tested by the peroxidase-antiperoxidase (PAP) method with anti-GFAP serum (DAKO) and by the avidin-biotin peroxidase complex (ABC) method with 68kd subunit of anti-NF antibody. All the cases were classified into three subtypes based on these immunohistochemical findings and were analyzed in relation to clinico-pathological features. Fifteen of thirty medulloblastomas contained GFAP positive cells, seventeen showed cells reacting to NF. The reactions for both proteins were present in eight medulloblastomas (PNET-BD, bipotential differentiation). Seventeen medulloblastomas reacted to only one protein (PNET-MD, monopotential differentiation). No reaction for either was found in five cases (PNET-NOS, not otherwise specified). The two year survival rate was 12.5% for PNET-BD compared to 49.2% for PNET-MD and 53.3% for PNET-NOS. Nine variables, i.e. age, tumor stage, metastatic stage, operation, radiotherapy, chemotherapy, histology, GFAP and NF, were analyzed using Cox's proportional hazard model. This revealed that the significant factors were tumor stage (p = 0.0002), GFAP (p = 0.0008) and operation (p less than 0.05). In conclusion, GFAP is the most important histological factor for prognosis and medulloblastoma without glial differentiation has a much better prognosis than one with glial differentiation.     

脑胶质瘤中p16蛋白、nm23蛋白及c-erbB-2蛋白的表达及其意义

目的 探讨p16蛋白、nm23蛋白及c-erbB-2蛋白在脑胶质瘤发生、发展中的作用。方法 应用免疫组织化学技术检测60例脑胶质瘤中p16蛋白、nm23蛋白及c-erbB-2蛋白的表达。结果 p16蛋白、nm23蛋白及c-erbB-2蛋白在脑胶质瘤和正常脑组织中的阳性表达率分别为43.3％和90％（P＜0.05）；36.7%和80％（P＜0.05）；41.7%和0（P＜0.05）。脑胶质瘤中p16蛋白及nm23蛋白缺失率在死亡组和生存组分别为73.7%和31.8%（P＜0.05）；84.2%和36.3%（P＜0.05）；c-erbB－2蛋白过度表达率在死亡组和生存组为68.4%和27.2%（P＜0.05）。结论 p16蛋白、nm23蛋白及c-erbB-2蛋白过度表达与脑胶质瘤发生、发展密切相关。     

蛋白质精氨酸甲基转移酶5和细胞分裂周期蛋白42在胃癌组织的表达及其临床意义

目的探讨蛋白质精氨酸甲基转移酶5(PRMT5)和细胞分裂周期蛋白42(Cdc42)在胃癌组织表达及临床意义。方法收集2014年6月至2020年8月山西医科大学第二医院病理学确诊的84例胃癌组织和对应癌旁组织,应用免疫组织化学方法检测PRMT5蛋白和Cdc42在标本中表达,结合临床资料采用χ²检验。结果PRMT5蛋白在胃癌组织中的表达率为73.81%(62/84),明显高于癌旁组织表达率[25.00%(21/84)],两者差异有统计学意义(χ²=40.030,P<0.01);Cdc42蛋白在胃癌组织中的表达率为80.95%(68/84),明显高于癌旁组织表达率[29.76%(25/84)],两者差异有统计学意义(χ²=44.535,P<0.01)。PRMT5表达水平与胃癌TNM分期、淋巴结转移呈明显相关(分别为χ²=6.149、5.497,P<0.05),Cdc42表达水平与胃癌TNM分期、淋巴结转移、组织学分化程度明显相关(分别为χ²=6.421、5.132、4.271,P<0.05)。结论胃癌组织中PRMT5蛋白和Cdc42蛋白表达上调,PRMT5和Cdc42有助于预测胃癌患者病情和预后。     

Comparison of C-reactive protein and high-sensitivity C-reactive protein levels in patients on hemodialysis

Chronic inflammation is highly prevalent in patients on hemodialysis (HD), as evidenced by increased levels of C-reactive protein (CRP). We compared CRP to high-sensitivity C-reactive protein (hs-CRP) to determine whether it has any clinical implications and prognostic significance in terms of mortality. CRP was measured using a standard immunoturbidometric assay on the COBAS? INTEGRA system and hs-CRP was measured using the Dade Behring on the Konelab Nephelometer in 50 patients on HD. CRP (≥6 mg/L) and hs-CRP (≥3 mg/L) levels were elevated in 30% and 54% of the patients, respectively. A significant correlation was noted between hs-CRP and CRP levels (r = 0.98, P <0.001). Deming regression analysis showed that the slope was near one (r = 0.90; 0.83-0.94) and that the intercept was small. Multivariate regression confirmed that age above 40 years (RR = 3.69, P = 0.027) and duration on HD greater than five years (RR = 3.71, P = 0.028) remained significant independent predictors of serum hs-CRP. Thirteen patients died during follow-up (26%). Multivariate Cox regression demonstrated that hs-CRP (RR = 1.062, P = 0.03) and CRP levels (RR = 1.057, P = 0.009) and age (RR = 1.078, P = 0.001) were the most powerful predictors of mortality. The CRP standard assay presents a reasonable alternative to the hs-CRP assay in patients on HD. The advantages of the CRP standard assay are its online and real-time availability as well as lower costs, particularly in developing countries.     

生物钟基因Clock、Bmal1蛋白在胆管癌组织中的表达及临床意义

目的:探讨人类生物钟基因hClock及hBmal1蛋白在人类胆管癌组织中的表达,并研究其表达与人类胆管癌的关系。方法:采用免疫组织化学法检测60例人类胆管癌组织及癌旁组织中hClock基因、hBmal1基因蛋白产物(Clock蛋白及Bmal1蛋白)的表达。结果:60例人胆管癌组织与相应癌旁组织中,Clock蛋白在胆管组织中阳性率为33.33%(20/60),在癌旁组织中阳性率为81.67%(49/60),两者阳性表达率差异有统计学意义(P0.05);而Bmal1蛋白在胆管癌组织中阳性率为73.33%(44/60),癌旁组织中阳性率为36.67%(22/60),两者阳性表达率差异也有统计学意义(P0.05)。Clock蛋白与Bmal1蛋白表达均与胆管癌TNM分期有关(P0.05)。在胆管癌组织中Clock蛋白与Bmal1蛋白表达呈负相关(r=-0.481,P0.05)。结论:Bmal1蛋白可能与人类胆管癌的发生有关,与侵袭、转移的关系有待深入研究,而Clock蛋白可能为胆管癌发生的抑制因素。     

Increased levels of protein C activity, protein C concentration, total and free protein S in nephrotic syndrome

Plasma protein C (PC) antigen concentration has been shown to be normal or increased in patients with proteinuria. However, the available data concerning PC anticoagulant activity in nephrotic syndrome (NS) are limited. We measured plasma PC antigen concentration. PC anticoagulant activity, total and free protein (PS) concentrations, and antithrombin III (AT-III) antigen concentration in 21 adult patients with NS. The results were compared with those obtained in a control group of normal volunteers. PC antigen concentration and its anticoagulant activity were significantly increased in the NS group when compared with the normal control group. Likewise, plasma total and free PS values were significantly higher in the NS patients than the corresponding values found in the control group. In contrast, plasma AT-III antigen concentration was significantly reduced in patients with NS. A negative correlation was found between plasma PC and AT-III levels. These observations suggest that increased plasma PC concentration and anticoagulant activity in NS may afford some protection against the thrombotic diathesis associated with antithrombin deficiency and other coagulation abnormalities in this otherwise hypercoagulable state.     

Energy and protein metabolism in sepsis and trauma

Energy and protein metabolism in septic and trauma patients has been extensively studied over the past 30 years. Despite this, a number of inconsistencies are present in the literature and it is difficult to formulate a clear global picture of this complex series of metabolic events. Conclusions from human studies have often been hampered by the utilization of small numbers of patients, and data from animal models of sepsis or trauma are often difficult to interpret. Over the past 5 years, the authors have performed a series of isotopic infusions in normal volunteers, and in patients with either sepsis or trauma, in order to gain a clearer understanding of energy and protein metabolism in severely stressed patients. This review summarizes the findings.     

Roles of protein kinase A and protein kinase G in synaptic plasticity in the visual cortex

Monocular deprivation leads to clear physiological and anatomical changes in the visual cortex known as ocular dominance plasticity. Protein kinase A (PKA) is necessary for ocular dominance plasticity, while protein kinase G (PKG) is not. We have now tested the role of PKA and PKG in long-term potentiation (LTP) and long-term depression (LTD). We have shown that PKA inhibitors have a major effect on both LTP and LTD in the visual cortical slices, whereas a PKG inhibitor affects LTP but not LTD. The PKA activator, 8-chloroadenosine-3',5'-monophosphorothioate, Sp-isomer (Sp-8-Cl-cAMPS), by itself induces a slowly rising form of LTP, which is occluded by theta-burst stimulation (TBS)-induced LTP. These results support the point that the PKA signaling pathway is crucial for neuronal plasticity in visual cortex, and the dissociation of the role of PKA and PKG in long-term synaptic plasticity in the visual cortex suggests that LTP alone is not sufficient to support ocular dominance plasticity, or LTD plays a more fundamental role than LTP in ocular dominance plasticity.