HIF-1α和VEGF在胆道闭锁患儿肝组织中的表达及意义

目的研究胆道闭锁(biliary atresia,BA)患儿肝组织中缺氧诱导因子(HIF-1α)和血管内皮细胞生长因子(VEGF)的表达及与血管生成和纤维化的关系,探讨其在BA发病中可能的作用机制。方法选取胆道闭锁患儿(BA组)肝组织15例、胆管扩张症患儿(CBD组)肝组织10例、BA发展为肝硬化接受肝移植患儿(LT组)肝组织10例。HE、Vimentin染色观察各标本的组织学改变并判定纤维化程度,CD34染色标记血管计数微血管密度(MVD),免疫组化法检测HIF-1α和VEGF在各组肝组织中的表达。结果 CBD组、BA组、LT组微血管密度分别为16.8±1.9、23.2±3.8、25.9±2.1。HIF-1α在肝细胞胞浆和部分胞核中表达,BA组HIF1-α的光密度(0.160 7±0.029 7)高于CBD组(0.150 4±0.146 3)和LT组(0.151 3±0.005 9),P0.05。VEGF在肝细胞、胆管、动脉壁的表达,BA组VEGF的光密度(0.162 9±0.012 9)高于CBD组(0.132 2±0.025 7)和LT组(0.146 2±0.015 2),P0.05。结论 HIF-1α、VEGF可能通过参与BA中的血管生成过程,促进肝纤维化。     

肝外胆道闭锁和胆管板畸形

肝外胆道闭锁(extra-hepatic biliary atresia)即胆道闭锁(biliary atresia, BA),是新生儿梗阻性黄疸的主要病因,其组织病理表现为肝门部及肝外胆道的纤维性炎症改变,肝外胆管闭塞或狭窄,肝脏门管区炎症浸润、部分纤维化及小胆管增生改变~([1]).     

CD4+T细胞因子在胆道闭锁患儿肝脏组织中的表达及其意义

目的 检测T淋巴细胞中的11种CD4+T细胞因子在胆道闭锁(biliary atresia,BA)患儿肝脏组织中的表达,以探讨其在胆道闭锁发病机制中的意义.方法 在病理的基础上,采用流式微球技术对29例BA及9例对照组患儿肝脏组织CD4+T细胞表达的11种细胞因子(IL-12p70、IFN-γ、IL-2、IL-10、IL-8、IL-6、IL-4、IL-5、IL-1β、TNF-α和TNF-β)同时进行定量检测,并对其代表因子IFN-γ进行免疫组化定位分析.结果 CD4+T细胞表达的11种细胞因子中,BA组患儿肝脏组织中IL-1β、IL-2、IL-6、IL-8、IFN-γ、TNF-α以及Th1细胞因子总量(IL-1β、IL-2、IL-8、IL-12p70、IFN-γ、TNF-α、TNF-β)与促炎因子总量(IL-1β、IL-2、IL-6、IL-8、IL-12p70、IFN-γ、TNF-α、TNF-β)分别为2920.69、1 106.01、152.22、12 614.22、834.18、161.29、19 504.55、19653.06,数值明显高于对照组的1 096.00、243.68、5.98、965.17、147.28、30.56、2 617.93、2 623.91,差异具有统计学意义(P＜0.05).结论 由CD4+Th1细胞及其细胞因子所介导的针对胆道上皮细胞的免疫炎症性疾病可能是造成胆道闭锁的主要原因之一.     

胆道闭锁患者肝内胆管γδT细胞和调节性T细胞浸润及意义

目的研究胆道闭锁(Biliary atresia,BA)患者肝组织中γδT细胞和调节性T细胞(Foxp3+Treg)的比例变化。方法采用免疫组织化学方法和流式细胞术观察和检测胆道闭锁患儿组(BA组)23例和对照组(CG组)12例肝组织中γδT细胞分布情况以及γδT细胞和Foxp3~+Treg细胞比例关系。结果免疫组织化学染色显示BA组肝脏汇管区胆管周围有大量γδT细胞和一定程度的Foxp3~+Treg细胞浸润。流式细胞术显示胆道闭锁肝组织中γδT细胞与Foxp3~+Treg细胞比例明显高于对照组(P0.05),且γδTT细胞与Foxp3~+Treg细胞比例呈显著负相关(P0.05)。结论胆道闭锁患儿肝组织中γδT细胞增多,或抑制Foxp3~+Treg细胞增值,促进了胆管的进行性炎症损伤。     

Toll样受体在胆道闭锁肝脏中的表达

目的 检测胆道闭锁(biliary atresia,BA)患儿肝脏组织中Toll样受体(TLRs)的表达情况,探讨其与胆道闭锁发生的关系.方法 应用RT-PCR和Westen blot方法检测13例BA患儿、7例胆总管扩张(CC)患儿和8例正常对照儿童(CO)肝脏组织中TLRs mRNA和蛋白的表达.结果 BA患儿肝脏组织TLR7表达明显高于CC组患儿和CO组患儿(P＜0.05);而TLR3的表达在BA组患儿和CC组患儿之间差异无统计学意义,略高于CO组患儿(P＞0.05).TLR4的表达在BA组患儿和CC组患儿之间差异无统计学意义(P＞0.05),但高于CO组患儿(P＜0.05).结论 胆道闭锁患儿肝组织中TLR3、TLR7、TLR4表达异常,可能在胆道闭锁胆管损伤中发挥作用.     

白细胞衍生趋化因子2在胆道闭锁肝纤维化中的表达及临床意义

目的研究白细胞衍生趋化因子2(leukocyte cell-derived chemotaxin 2,LECT2)在胆道闭锁(biliary atresia,BA)诊断中的价值,探讨其对BA肝纤维化的影响。方法选取2018年1月至2019年1月天津市儿童医院普外科手术患儿20例,其中,男4例,女16例,留取患儿术中组织样本。BA患儿18例,先天性胆管扩张症(congenital biliary dilatation,CBD)患儿2例。将BA患儿的组织样本作为BA组织组,CBD患儿的组织样本作为CBD组织组。两组手术组织样本通过免疫组织化学染色检测LECT2、CD31在肝脏中的表达程度。根据本研究血液样本纳入标准,选取2018年6月至2019年1月天津市儿童医院普外科门诊首诊的黄疸患儿及门诊检查的婴儿共31例,其中,男18例,女13例。经胆管造影确诊为BA的患儿有17例,作为BA组,非BA的黄疸患儿7例,作为非BA组;体检肝功能正常且无感染性疾病的婴儿7例作为对照组。3组中所有患儿均留取3 ml新鲜外周血液,通过ELISA法评估血清LECT2的水平。结果肝组织免疫组织化学检测结果:①与C...     

The expression of interleukin-33 in the serum and liver tissue of the patients with biliary atresia

目的 研究胆道闭锁(BA)血清及肝脏组织中白介素-33(IL-33)的表达及意义.方法 选取18例BA与12例无黄疸症状且肝功能正常的胆总管囊肿(CC)患儿血清和肝脏标本进行对比研究.应用酶联免疫吸附试验检测血清中IL-33的表达水平.荧光定量RT-PCR技术和免疫印迹技术分别检测肝脏组织中IL-33 mRNA及蛋白表达水平.结果 BA组血清中IL-33的表达(791.0±22.22)pg/ml明显高于CC组的(607.1±20.68) pg/ml(P＜0.0001);并与γ-谷氨酰转移酶呈正相关(r=0.629,P=0.005).BA组肝组织中IL-33 mRNA表达0.0420±0.0061明显高于CC组的0.0220±0.0027(P=0.0181).BA组肝组织中IL-33蛋白表达0.4683±0.0188亦明显高于CC组的0.3433±0.0293(P=0.0137).结论 IL-33在BA组血清及肝组织中表达均明显升高,可能在BA炎症发生及发展过程中发挥重要作用,值得进一步研究.     

婴儿阻塞性胆管病肝组织与胆管构形的研究

目的：通过病理学方法，作出肝外胆道闭锁的诊断和预后判定。方法：对２３例婴儿阻塞性胆管病和５例对照的肝组织，按病理诊断和年龄分组，进行肝组织的二维病理学研究和肝内胆管三维构形观察。结果：肝外胆道闭锁与狭窄和新生儿肝炎肝组织的病变相似，仅程度不同。不同年龄组间，胆管增生、汇管区面积和肝纤维化及肝硬化有显著性差异。胆道闭锁的大月龄组中胆道病变和胆栓明显，新生儿肝炎时肝细胞坏死更突出。肝内胆管的三维构形表明，胆道闭锁时增生赫令管多数管腔开放，并互相连接成网络状；少数赫令管形成膨大盲端和局部小叶间胆管形成微囊肿。结论：①阻塞性胆管病时，肝纤维化、胆管增生和汇管区面积与患儿月龄有关；②赫令管形成网络状暗示胆道阻塞，结合胆管的病变和胆栓有助于诊断胆道闭锁；③胆管的微囊肿和赫令管膨大盲端提示胆道闭锁预后差     

胆道闭锁肝内iNOS及其调控因子异常表达与进行性肝损伤的相关性

目的 研究胆道闭锁(BA)患儿肝内诱导型一氧化氮合酶(iNOS)及其上下游调控因子表达情况,并探讨其与BA进行性肝损伤发生的关系.方法 应用免疫组织化学染色法对2002年10月至2007年3月在本院行Kasai手术的38例BA患儿与16例对照儿童肝组织iNOS表达情况进行研究;应用ELASA法对BA患儿和对照组外周血总一氧化氮(NO)代谢产物浓度进行测定;应用TUNEL法对BA患儿和对照组肝内胆管上皮凋亡指数进行测定;应用免疫印记法对BA患儿和对照组肝组织NF-κB表达进行半定量分析.结果 iNOS在BA患儿肝组织异常高表达,强度为0.30±0.08,而在对照组肝组织不表达.BA患儿外周血总NO代谢产物浓度为(90.40±12.46)mol/L,明显高于对照组的(63.67±5.78)μmol/L,且BA组总NO代谢产物浓度与血清ALT水平[(152.76±29.59)U/L]呈强正相关(r=0.97).BA组肝内胆管上皮凋亡指数(54.00±11.67)%远高于正常对照组(20.72±5.63)%,且与肝组织iNOS表达强度呈强正相关(r=0.99).NF-κB出在BA患儿肝组织中的表达(0.74±0.06)明显高于正常对照组(0.22±0.03),且与iNOS表达强度呈强正相关(r=0.97).结论 iNOS异常高表达在BA患儿进行性肝损伤中发挥重要作用,该作用是由iNOS及其上下游调控因子NF-κB、NO共同作用所实现.     

胆道闭锁肝内胆管上皮E-cadherin的表达及其与细胞凋亡相关性研究

目的研究胆道闭锁(biliaryatresia,BA)肝内胆管上皮Ecadherin的表达及胆管上皮细胞凋亡情况,初步探讨其与BA发生的关系。方法应用Ecadherin免疫组化染色方法和末端脱氧苷酸转移酶介导的脱氧三磷酸尿苷(Dutp)缺口末端标记技术(TUNEL法)观察38例胆道闭锁患儿与16例正常对照儿童肝内胆管上皮Ecadherin表达及胆管上皮细胞凋亡情况。结果胆道闭锁患儿肝内胆管上皮Ecadherin表达强度0.33±0.12较正常对照0.62±0.20显著降低(P<0.01),胆管上皮细胞凋亡指数为0.5174±0.1993明显高于正常对照0.1234±0.1932(P<0.01),BA组肝内胆管上皮Ecadherin表达强度与胆管上皮细胞凋亡指数呈显著负相关(r=-0.853)。结论BA发生与肝内胆管上皮Ecadherin异常降低有关,可能是通过异常降低的Ecadherin上调胆管上皮细胞凋亡数量,导致肝内胆管发育障碍,产生“胆管板畸形”的方式来实现的。     

Allergic factors associated with the development of asthma and the influence of cetirizine in a double-blind, randomised, placebo-controlled trial: First results of ETA®

There is a common progression known as the allergic march from atopic dermatitis to allergic asthma. Cetirizine has several antiallergic properties that suggest a potential effect on the development of airway inflammation and asthma in infants with atopic dermatitis. Methods. Over a two year period, 817 infants aged one to two years who suffered from atopic dermatitis and with a history of atopic disease in a parent or sibling were included in the ETAC^® (Early Treatment of the Atopic Child) trial, a multi-country, double-blind, randomised, placebo-controlled trial. The infants were treated for 18 months with either cetirizine (0.25mg/ kg b.i.d.) or placebo. The number of infants who developed asthma was compared between the two groups. Clinical and biological assessments including analysis of total and specific IgE antibodies were performed. Results. In the placebo group, the relative risk (RR) for developing asthma was elevated in patients with a raised level of total IgE (≥ 30 kU/I) or specific IgE (≥ 0.35 kUA/I) for grass pollen, house dust mite or cat dander (RR between 1.4 and 1.7). Compared to placebo, cetirizine significantly reduced the incidence of asthma for patients sensitised to grass pollen (RR = 0.5) or to house dust mite (RR = 0.6). However, in the population that included all infants with normal and elevated total or specific IgE (intention-to-treat - ITT), there was no difference between the numbers of infants developing asthma while receiving cetirizine or placebo. The adverse events profile was similar in the two treatment groups. Discussion. Raised total IgE level and raised specific IgE levels to grass pollen, house dust mite or cat dander were predictive of subsequent asthma. Cetirizine halved the number of patients developing asthma in the subgroups sensitised to grass pollen or house dust mite (i.e. 20% of the study population). In view of the proven safety of the drug, we propose this treatment as a primary pharmacological intervention strategy to prevent the development of asthma in specifically sensitised infants with atopic dermatitis.     

�¶�֢��ϵ�ϰ���ע��ȱ�ݶද�ϰ������ڵ�ת��

孤独症谱系障碍(autistic-spectrum disorders,ASDs)近年来患病率逐年攀升至1%左右,其症状往往伴随终生,成为严重威胁儿童健康和发展的神经发育性疾患;注意缺陷多动障碍(attention deficit hyperactivity disorder,ADHD)是儿童期最常见的精神障碍,国内报道患病率为4.13%～5.83%,其症状可延续至青少年期,甚至到成年期[1]。这两类精神障碍在成年期的临床表现、共患病、治疗策略和预后与儿童期有哪些不同呢?本文通过回顾相     

EXCITING NEW TREATMENT APPROACHES FOR PATHYPHYSIOLOGIC MECHANISMS OF SICKLE CELL DISEASE

During the past several decades, our understanding of the complex pathophysiology of vasoocclusion associated with sickle cell disease has improved greatly. Interaction of genes, hemoglobin molecules, red cell membrane and metabolic changes, cell-cell interactions and cell-plasma interactions, red cell adhesion to vascular endothelium, activation of coagulation, and vascular reactivity play a role in vaso occlusion. Penicillin prophylaxis of pneumococcal infections and appropriate use of blood transfusions and other supportive measures improved survival of sickle cell patients. Hydroxyurea made a major impact on sickle cell therapy when it was shown to decrease acute painful episodes, acute chest syndrome, and the need for blood transfusion in adults. Significant experience in the use of hydroxyurea has been accumulated in older children. The benefits and risks of hydroxyurea for younger children and long-term risks in all patients will be evaluated in future investigations. Other promising therapies include butyrate compounds, clotrimazole, magnesium supplementation, poloxamer 188, antiadhesion agents, anticoagulant approaches, and nitric oxide. Hemopoietic transplantation remains the only curative therapy. However, several transgenic mouse models are available for studies of gene therapy or other treatment approaches on biochemical, cellular, and pathologic effects of mutant genes.     

Infiltrations of Epstein-Barr virus-carrying cells in granular lymphocyte-proliferative disorders corresponding to chronic active Epstein-Barr virus infection

A 21-year-old man with granular lymphocyte-proliferative disorders (GLPD) associated with chronic active Epstein-Barr virus (EBV) infection is described. Chromosomal analyses revealed several clonal abnormalities and two of them were mainly repetitious. High copy numbers of monoclonal EBV genome were also detected in the proliferative large granular lymphocytes (LGLs), indicating the monoclonal expansion of EBV-infected LGLs. The patient had an indolent course for several years, and there was no evidence of infiltrations of his bone marrow until the end stage. At autopsy, microscopic studies revealed marked infiltrations of LGL in the liver and spleen, and the infiltrating cells were NK-cell immunophenotype. The infiltrated LGLs showed latency I.     

LUTEINIZING HORMONE RECEPTOR MUTATIONS IN DISORDERS OF SEXUAL DEVELOPMENT AND CANCER

Human male sexual development is regulated by chorionic gonadotropin (CG) and luteinizing hormone (LH). Aberrant sexual development caused by both activating and inactivating mutations of the human luteinizing hormone receptor (LHR) have been described. All known activating mutations of the LHR are missense mutations caused by single base substitution. The most common activating mutation is the replacement of Asp-578 by Gly due to the substitution of A by G at nucleotide position 1733. All activating mutations are present in exon 11 which encodes the transmembrane domain of the receptor. Constitutive activity of the LHR causes LH releasing hormone-independent precocious puberty in boys and the autosomal dominant disorder familial male-limited precocious puberty (FMPP). Both germline and somatic activating mutations of the LHR have been found in patients with testicular tumors. Activating mutations have no effect on females. The molecular genetics of the inactivating mutations of the LHR are more variable and include single base substitution, partial gene deletion, and insertion. These mutations are not localized and are present in both the extracellular and transmembrane domain of the receptor. Inactivation of the LHR gives rise to the autosomal recessive disorder Leydig cell hypoplasia (LCH) and male hypogonadism or male pseudohermaphroditism. Severity of the clinical phenotype in LCH patients correlates with the amount of residual activity of the mutated receptor. Females are less affected by inactivating mutation of the LHR. Symptoms caused by homozygous inactivating mutation of the LHR include polycystic ovaries and primary amenorrhea.     

Resurgence of measles in Singapore: profile of hospital cases

OBJECTIVE: To ascertain the profile of cases of measles seen at a general hospital during a recent outbreak that occurred despite a measles vaccination program. METHODOLOGY: A retrospective study from January 1991 to March 1998. All patients with measles (ICD code 055. 9) seen at the emergency unit or as inpatients were included. RESULTS: There were 87 cases identified. The diagnosis was clinical in all and proven serologically in 71%. Eighty-five per cent of the cases occurred between January 1997 and March 1998. There was a bi-modal age distribution with peaks in the very young (相似文献   

Personality profiles and heart rate variability (vagal tone) in children with recurrent abdominal pain

The aim of the study was to explore psychological factors and autonomic activity in children with recurrent abdominal pain and to compare them with those in a control group of healthy children. The Personality Inventory for Children was used for assessment of developmental, emotional and psychosocial factors in 25 children with recurrent abdominal pain (age, 7-15 y). Parasympathetic and sympathetic functions in these children and in 23 healthy control subjects (age, 7-13 y) were also investigated, non-invasively using a computerized polygraph. Vagal tone (parasympathetic function) was indexed by calculation of respiratory sinus arrhythmia in beats/min. Skin conductance (sympathetic function) was recorded by the constant current method. On the Personality Inventory for Children, 16 patients had high scores on somatic concern. Several patients had scores in the clinical range for depression, withdrawal and anxiety, but the mean scores for these personality profile scales were well within the normal range of healthy children. Interestingly, there was a spike on the L (Lie)-scale for most of the patients and 15 patients had scores above or close to the clinical cut-off value. As compared with the scores in healthy children, vagal tone and sympathetic tone were normal. Conclusion: Many children with recurrent abdominal pain have scores in the clinical range for depression, withdrawal, anxiety and L-scale indicating coping problems, denial and a trend towards somatic concern that may contribute to the evolution of abdominal pain. Autonomic nerve activity was not disturbed in these children.     

Overcoming surfactant inhibition with polymers

Inhibition of the function of pulmonary surfactant in the alveolar space is an important element of the pathophysiology of many lung diseases, including meconium aspiration syndrome, pneumonia and acute respiratory distress syndrome. The known mechanisms by which surfactant dysfunction occurs are (a) competitive inhibition of phospholipid entry into the surface monolayer (e.g. by plasma proteins), and (b) infiltration and destabilization of the surface film by extraneous lipids (e.g. meconium-derived free fatty acids). Recent data suggest that addition of non-ionic polymers such as dextran and polyethylene glycol to surfactant mixtures may significantly improve resistance to inhibition. Polymers have been found to neutralize the effects of several different inhibitors, and can produce near-complete restoration of surfactant function. The anti-inhibitory properties of polymers, and their possible role as an adjunct to surfactant therapy, deserve further exploration.     

Understanding infant formula

The World Health organisation recommends breast feeding infants for the first six months of life. When this breast feeding does not occur either through parental choice or medical need, infant formulas will be required. There is a bewildering array of formulas on the UK market for many different requirements. When faced with an unsettled infant many parents (and healthcare professionals) will experiment with the infant formula available and then attend the paediatric clinic looking for help and advice. It is therefore essential that paediatricians understand what milks are available and what the key differences between different products are. This review attempts to provide a simple guide through many of the formulations currently available in the UK; and offers advice for the dietary management of the child with extra calorie requirements, infants with cow's milk protein allergy, gastro oesophageal reflux disease, apparent unresolved hunger and infantile colic. Whatever the underlying condition, there is likely to be an infant formula that is suitable in this generation of ever expanding formulations.