先天性肠闭锁病理组织学研究

目的；分析先天性肠闭锁的病理组织学改变及其对肠道的影响。以探讨肠闭锁手术的切除范围。方法；对１６例行天性肠闭锁手术切除之远近端肠管地ＨＥ染色，光镜下观察肠壁各层工及神经组织蝗改变及其范围。结果：在各型肠闭锁中，远近端肠管除肠壁厚度有改变外，各层神经丛及神经节细胞数均较正常明显减少，近端改变范围大于１０ｃｍ，远端改变局限于２ｃｍ内，在此范围内，随着远离闭锁盲端，上述指标均有逐渐增加的趋势。结论本组结     

儿童肠神经节发育异常症临床病理分析

目的探讨儿童先天性巨结肠(HD)、肠神经元性发育异常症(IND)和肠神经节减少症(IH)的临床和病理特征。方法回顾性分析238例肠神经节发育异常症患儿的临床资料和病理切片,比较其发病年龄、性别、病变累及肠段和预后等的差异。结果 238例患儿中,138例(58.0%)由直肠黏膜活检明确诊断。其中单纯HD122例,中位确诊年龄9个月,男女比为4.3︰1,均未累及全结肠;单纯IND 45例,中位确诊年龄14个月,男女比为1.05︰1,33.3%累及全结肠;单纯IH 2例,分别为12、18岁的男性,全部累及全结肠;HD合并IND 59例,中位年龄13个月,男女比5.56︰1,16.9%累及全结肠;HD合并IH 10例,中位年龄为11.5个月,全部为男性,80.0%累及全结肠。五组患儿诊断时年龄、男女性别比、累及全结肠比例以及患儿治愈率差异有统计学意义(P均0.01)。结论直肠黏膜活检是诊断儿童肠神经节发育异常症的主要方法。HD发生率较高,病情较轻,预后好;单纯IH和HD合并IH发生率最低,病情最重,预后最差;单纯IND和HD合并IND居于前两组之间。     

先天性肠闭锁肠神经节细胞NT-3蛋白表达研究

目的了解神经节细胞在先天性小肠闭锁中的分布情况,并探讨其临床意义。方法应用免疫组化技术检测15例先天性小肠闭锁患儿肠壁内NT-3的表达情况,并以正常小肠标本作为对照。结果肠闭锁组肠壁肌间神经丛中神经节细胞NT-3蛋白表达明显低于对照组(t'=9.90,P<0.05)。结论小肠闭锁近端肠壁内神经节细胞减少和神经干的变细可以影响闭锁区域肠道的功能,是病人术后肠道功能不良的原因所在。     

神经干细胞移植治疗肠无神经节细胞症的研究进展

先天性巨结肠（Hirschsprung’s disease,HSCR）也称结肠无神经节细胞症,其在欧洲、亚洲以及北美洲的发病率在1／5000左右,而在具有相应同种基因背景的人群中可能会有更高的发病率。HSCR的主要发病机制是远端结肠神经节细胞缺失或减少,造成病变肠段蠕动功能障碍,     

小儿神经节细胞减少症肠壁肌间神经丛形态定量研究

目的研究神经节细胞减少症的形态定量特征。方法对15例小儿节细胞减少症、14例无神经节细胞症及14例正常神经分布的肠壁组织进行常规石蜡切片,并作HE染色、NSE及S-100免疫组织化学染色,在光学显微镜图像分析系统下对三组标本的肠壁肌间神经丛组织进行形态定量测定并对各组测量参数进行统计学的分析比较。结果节细胞减少症肠肌神经丛中每毫米肠壁的平均神经节细胞数是1.52个(仅为正常组的24.3%),其每毫米肠壁的平均神经丛面积是(5.61×103)μm2(为正常组的17.3%),无神经节细胞症神经丛面积亦有明显减少,数量更少,NSE、S-100免疫组织化学染色可帮助正确辨别神经节细胞。结论肠壁肌间神经丛中神经节细胞数量减少的同时伴有神经丛面积的减小是节细胞减少症的特征性改变,肠肌神经丛的形态定量测定可作为神经节细胞减少症的客观诊断依据,彻底切除节细胞减少的肠段对于根治此症具有重要意义。     

神经节细胞减少症的诊断与手术治疗

目的了解神经节细胞减少症的诊断与手术治疗效果。方法对17例该病患儿进行回顾性分析及随访。结果本组17例单纯性神经节细胞减少症全部行钡灌肠X线检查,共有9例可见狭窄段、扩张段,其中2例可见明显移行段。15例行直肠肛管测压有5例未出现直肠肛管抑制反射。16例行乙酰胆碱酯酶测定仅3例阳性。多处全层活检可准确诊断该病。术后2例发生小肠结肠炎,经保守治疗痊愈。其他患儿均未出现切口裂开、肠瘘、污粪、便秘复发。结论全层活检是诊断该病的可靠方法,病变肠段切除、结肠直肠吻合术治疗本病可获满意的疗效。     

细胞焦亡参与肺动脉高压病理生理的研究进展

<正>细胞死亡是机体生长发育的重要过程,分为被动死亡和主动死亡,即细胞坏死和细胞程序性死亡。细胞焦亡（pyroptosis）是细胞程序性死亡的一种重要类型,于2000年由Brennan等首次命名[1]。肺动脉高压（pulmonary arterial hypertension,PAH）全球人口患病率约为的1%,其中80%的患者生活在发展中国家[2]。PAH早期不易被发现,目前尚无根治的方法,患者出现右心功能衰竭甚至死亡,预后极差。多项研究表明细胞焦亡参与肺动脉细胞的死亡过程,从而引发或加剧PAH[3-6]。这对于了解PAH的发病机制,     

组织蛋白酶D和S-100蛋白在先天性巨结肠症中的表达

先天性巨结肠症（Hirschsprung’s disease，HD）是小儿科常见的消化道畸形，以远端病变段肠管神经节细胞缺如、肠道神经支配发生紊乱以及此节段的持续性收缩为特征。在HD的病理诊断中，有部分病例尤其是新生儿病例，南于肠壁神经系统发育不完全，神经节细胞欠成熟，形态不典型，与神经丛中施万细胞（Schwann cell，SCs）及周围细胞难以鉴别，光镜下不易明确诊断。     

先天性巨结肠症术后小肠结肠炎发生与合并神经节细胞减少症的相关性分析

目的探讨先天性巨结肠症（HD）合并神经节细胞减少（HYP）与术后肠炎发生的相关性。方法对97例在我院行巨结肠根治术的患儿进行随访，随访时间1．5～8年，平均3．4年。分为两组：A组70例，为HD；B组27例，为HD合并HYP。对其排便功能与术后小肠结肠炎（EC）的发生情况进行分析比较。结果A组术后发生肠炎有8例（11．4%），B组发生肠炎有11例（40．7％），两组相比较差异有统计学意义（P〈0．005）。按照李正的评分系统，A组排便功能评分为优者比率为85．7％，明显高于B组的62．9％（P〈0．05）。A组便秘复发率为2．9％（2／70），B组为14．8％（4／27），但两者之间差异无统计学意义（P〉0．05）。结论HD合并HYP患儿术后较HD更易发生小肠结肠炎，完全切除HYP肠管可降低EC的发生率，减轻肠炎发生的程度。     

The evaluation of meconium disease by distribution of cathepsin D in intestinal ganglion cells

Meconium disease (MD) results in intestinal obstruction in the neonate where tenacious meconium is found in the distal ileum and proximal colon. The obstructive symptoms improve at several days of age after some of the meconium is passed. We observed premature infants with MD who underwent ileostomy for intestinal obstruction due to tenacious meconium. Afterward, meconium was passed well and the clinical symptoms improved. After closing the ileostomy, growth and defecation became normal. The MD in our cases was documented by histologic changes in the maturation of ganglion cells observed at the time of ileostomy creation and closure. For an objective evaluation of the maturation of intestinal ganglion cells (IGC), we attempted to distinguish immature from mature cells by the expression of cathepsin D. We examined the distribution of cathepsin D in IGC in patients with MD to test the hypothesis that ganglion-cell immaturity might be related to MD. In ganglion cells at the time of ileostomy, cathepsin D was detected in the perinuclear cytoplasm (immature staining pattern), while at the time of ileostomy closure it was detected in intense granules throughout the cytoplasm (mature staining pattern). We propose that it would be possible to evaluate the maturation of IGC by the intracellular distribution of cathepsin D in MD and suggest that immaturity of IGC might be the cause of MD. Accepted: 28 June 1999     

Plasma levels of the von Willebrand factor-cleaving protease in physiological and pathological conditions in children

The hemolytic uremic syndrome (HUS) and thrombotic thrombocytopenic purpura (TTP) are rare disorders characterized by thrombocytopenia, hemolytic anemia, and ischemic organ failure due to thrombotic occlusions in arterioles. The recent observation that a von Willebrand factor-cleaving protease (VWF-CP) is low in the plasma of patients with TTP but normal in those with HUS has potentially offered a new specific tool for differential diagnosis. In this study, the authors evaluated the plasma levels of the VWF-CP during the neonatal state and healthy childhood and in some pathological pediatric conditions. The protease was measured in 16 healthy newborns, 20 healthy children aged 5-18 years, patients with diabetes mellitus type1 ( n = 7), acute viral hepatitis ( n = 10), chronic viral hepatitis ( n = 10), transfusion-dependent β-thalassemia major ( n = 10), acute varicella infection ( n = 11), the nephrotic syndrome ( n = 11), and familial Mediterranean fever ( n = 10). Mean protease levels were significantly lower in newborns than in healthy children (50.5 ±16.1% vs. 83.3 ±16.3%)( p = .0001). In patients with acute viral hepatitis, protease levels were also significantly reduced (40.2 ±27% v s. 83.3 ±16.3% in healthy children)( p = .0001). Other patient groups had normal protease levels. In conclusion, low protease levels are far from being a specific beacon for TTP. The current paradigm that a single laboratory test may enable physicians to distinguish TTP from HUS seems to be challenged by these and other findings.     

A case of immature teratoma originating in intra-abdominal undescended testis in a 3-month-old infant

Teratomas in an undescended testis are rare in infants. This report was the youngest case of immature teratoma originating in intra-abdominal undescended testis. A 3-month-old infant with cryptorchism was seen because of an asymptomatic palpable mass in the right abdomen. Ultrasonography and computed tomography revealed a multicystic large tumor with focal calcifications in the right side and serum tumor markers within normal limits. Complete resection of the tumor was performed and the histopathological diagnosis was made as immature teratoma of the right testis. Because retroperitoneal lymph nodes metastasis was observed in 3-month follow-up postoperatively, retroperitoneal lymphadenectomy and chemotherapy including bleomycin, etoposide, and cisplatin were performed. Presently, the infant has been free of recurrence for 3 years. We suggest that nonpalpable testis should undergo a careful evaluation and prompt resolution and that the subsequent finding of an intra-abdominal mass should make us think on the possibility of intra-abdominal testicular germ cell tumor. Postoperative adjuvant chemotherapy in combination with complete resection of the tumor is necessary for pediatric immature teratomas originating in intra-abdominal undescended testis.     

外周蛋白和组织蛋白酶D在先天性巨结肠症中的表达

目的:观察外周蛋白(peripherin，PR)和组织蛋白酶D(cathepsin D，CD)在Hirschsprung症(HD)肠壁中的表达并探讨其诊断价值。方法：应用免疫组织化学染色观察9例HD及5例对照组患儿结肠。结果：在正常结肠肠壁内有CD或PR阳性神经节细胞，肠壁各层均有PR阳性神经纤维，但无CD阳性神经纤维染色。在无神经节细胞肠段的肠壁内缺乏CD或PR阳性神经元，亦无CD阳性神经纤维染色，肌层和黏膜下层内PR阳性神经纤维明显减少或缺如。结论：CD和PR是肠神经节细胞特异性较高的标志物，二者的免疫组织化学染色将有助于HD及其同源病的诊断。     

围产期反复感染对未成熟鼠脑发育的影响

目的 探讨围产期反复感染对未成熟脑发育的影响及相关机制.方法 将6只C57BL6 孕小鼠随机分为宫内感染组、反复感染组与正常对照组.母鼠于妊娠第18天单次腹腔注射LPS(0.5 mg/kg)制成宫内感染脑损伤模型;反复感染组取宫内感染母鼠所生仔鼠,于生后3~12 d每日腹腔注射单剂LPS(0.5 mg/kg)制成围产期反复感染脑损伤模型;对照组用等量生理盐水替代LPS在上述相同时间点给予母鼠和仔鼠腹腔注射.各组仔鼠于生后13 d分别评估早期神经行为改变.评估完成后处死取脑组织检测脑重变化;焦油紫染色进行神经病理学评估;Western blot检测肿瘤坏死因子-α(TNF-α)、半胱氨酸蛋白酶-3(Caspase-3)和髓鞘碱性蛋白(MBP)的表达变化.结果 与对照组和宫内感染组相比,围产期反复感染组仔鼠脑重下降(P<0.05),且表现出较为明显的神经病理学改变.Western blot结果显示反复感染组TNF-α和Caspase-3的表达水平均高于宫内感染组与正常对照组(均P<0.01);而MBP表达量却低于宫内感染组与正常对照组(P<0.01).神经行为学检测结果显示,生后13 d时反复感染组小鼠步态反射、翻正反射与负向趋地反射完成时间均长于宫内感染组与正常对照组(均P<0.05).结论 围产期反复感染加重未成熟脑组织内的炎症反应与神经细胞凋亡,是导致未成熟脑白质损伤的重要危险因素.     

Mature and immature teratomas: results of the first paediatric Italian study

Teratoma is the most common germ cell tumour in childhood; mature (MT) and immature teratomas (IT) are benign tumours, but if they recur, they can be in some cases malignant. The aim of this paper is to evaluate Italian patients with MT and IT enrolled from 1991 to 2001, in a prospective multicentric study. One hundred and eighty-three patients, observed in 15 Italian Centers of Paediatric Oncology and three Paediatric Surgical Units were enrolled. Clinical data, treatment and results were all analysed. Initial evaluation and subsequent follow up included clinical examination, tumour markers and imaging procedures. Surgical resection was recommended for all the tumours. Histology was centrally reviewed and IT was classified as grading 1-3. Chemotherapy (CT) with Vinblastine, D: -actinomycin and cyclophosphamide was indicated for extra-testicular IT grade 2 or 3. MT was diagnosed in 127 patients (93 F and 34 M, age 1-192 months, median 24): 58 patients had gonadic tumour (23 testicular, 35 ovaric), 69 extragonadic (45 sacrococcygeal, 11 mediastinic, 7 retroperitoneal, 6 in other sites). A complete resection was performed in 117 patients, a partial resection in eight patients and biopsy in one. IT was diagnosed in 56 patients (34 F, 22 M, age 1-168 months, median 7). The T grading was 1 in 14 cases, 2 in 26, 3 in 16; 28 had gonadic T (17 ovary, 11 testis), 28 extragonadic (sacrococcygeal 19, mediastinic 3, retroperitoneal 2, other sites 4). CT was administered in eight patients; 15/182 patients relapsed (1 in a metastatic site) and in 5/15 the relapse showed malignant histology. Seven MT (5.5%) relapsed (five sacrococcygeal, one retroperitoneal, one mediastinic): surgery at diagnosis had been complete in five and with residual in two; the relapse was malignant in two patients with sacrococcygeal (sc) tumours, who had a complete resection and a partial resection respectively. Eight IT (14.2%) relapsed (four ovary, three sc, one retroperitoneal). The initial surgical resection had been complete in one, with residual in six, and a biopsy had been performed in one. A malignant recurrence occurred in two patients with sc tumours (after partial resection in one and after biopsy + CT in one) and in one patient with ovarian IT after a partial resection. All the patients underwent surgical excision of the recurred mass; CT according to Protocol for Malignant GCT was administered to those who had malignant recurrence; 122/126 patients with MT and 53/56 with IT are alive without disease with a follow up of 8-144 months (median 56). Two patients with malignant relapse (one with sc MT, one with sc IT) died because of the progression of the disease. Another two died due to severe malformations (one MT, one IT) and three were lost to follow up (two MT, one IT). The overall survival (OS) at 10 years is 98% (95% CI 93.9-99.4); the event free survival (EFS) is 90.4% (95 CI 84.8-94.0). At Cox analysis no significant difference in EFS was found regarding age and site of the primary tumour, while females (P = 0.011), patients with grade 1-3 histology (P = 0.025) and patients with incomplete resection appeared at higher risk of death or relapse (P < 0.001), with a seven, three and eightfold increase in risk, respectively. Our data showed that incomplete resection and female gender are important risk factors for relapse or death, more so than IT histology. The number of patients treated with CT is not sufficient to evaluate the efficacy of CT in avoiding malignant relapse.     

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??Proteinuria??as an important clinical manifestation of kidney disease??is also an independent risk factor for the progression of renal disease. So the control of proteinuria has become an important target for diagnosis and treatment of kidney disease. Physiological proteinuria??which in the past is different from the pathological proteinuria??is considered to be a benign change. But in clinical practice??there is increasing evidence that some of the physiological proteinuria also has a poor prognosis. In this paper??we put forward the definition criterion of physiological proteinuria??and give the corresponding follow-up advice??in order to avoid the judgment of the simple benign change of physiological proteinuria.