Clinical and molecular insights into Glanzmann's thrombasthenia in China

Glanzmann's thrombasthenia (GT) is a rare bleeding disorder characterized by spontaneous mucocutaneous bleeding. The disorder is caused by quantitative or qualitative defects in integrin αIIbβ3 (encoded by ITGA2B and ITGB3) on the platelet and is more common in consanguineous populations. However, the prevalence rate and clinical characteristics of GT in non‐consanguineous populations have been unclear. We analyzed 97 patients from 93 families with GT in the Han population in China. This analysis showed lower consanguinity (18.3%) in Han patients than other ethnic populations in GT‐prone countries. Compared with other ethnic populations, there was no significant difference in the distribution of GT types. Han females suffered more severe bleeding and had a poorer prognosis. We identified a total of 43 different ITGA2B and ITGB3 variants, including 25 previously unidentified, in 45 patients. These variants included 14 missense, 4 nonsense, 4 frameshift, and 3 splicing site variants. Patients with the same genotype generally manifested the same GT type but presented with different bleeding severities. This suggests that GT clinical phenotype does not solely depend on genotype. Our study provides an initial, yet important, clinical and molecular characterization of GT heterogeneity in China.     

Novel recessive PDZD7 biallelic mutations in two Chinese families with non‐syndromic hearing loss

Autosomal recessive non‐syndromic hearing loss (ARNSHL) is a highly heterogeneous genetic condition. PDZD7 has emerged as a new genetic etiology of ARNSHL. Biallelic mutations in the PDZD7 gene have been reported in two German families, four Iranian families, and a Pakistani family with ARNSHL. The effect of PDZD7 on ARNSHL in other population has yet to be elucidated. Two Chinese ARNSHL families, each of which had two affected siblings, were included in this study. The families underwent target region capture and high‐throughput sequencing to analyze the exonic, splice‐site, and intronic sequences of 128 genes. Furthermore, 1751 normal Chinese individuals served as controls, and 122 Chinese families segregating with apparent ARNSHL, who had been previously excluded for variants in the common deafness genes GJB2 and SLC26A4, were subjected to screening for candidate mutations. We identified a novel homozygous missense mutation (p.Arg66Leu) and novel compound heterozygous frameshift mutations (p.Arg56fsTer24 and p.His403fsTer36) in Chinese families with ARNSHL. This is the first report to identify PDZD7 as an ARNSHL‐associated gene in the Chinese population. Our finding could expand the pathogenic spectrum and strengthens the clinical diagnostic role of the PDZD7 gene in ARNSHL patients.     

Functional independence of Taiwanese children with Prader–Willi syndrome

Prader–Willi syndrome (PWS) is a genetic disorder with obesity, developmental delay, short stature, and behavioral abnormalities. The study aimed to assess the functional independence in children with PWS. The Functional Independence Measure for Children (WeeFIM) was used to evaluate 81 children with PWS (44 boys and 37 girls) with a median age of 11 years 1 month (range 2 years 8 months to 20 years 2 months) were recruited between January 2013 and December 2016. The mean total WeeFIM score was 103.8 (maximum 126). Sixty‐five patients (80%) had deletion type PWS, 16 (20.0%) had nondeletion type. The scores were 103.6 ± 18.5 for deletion and 104.8 ± 18.3 for nondeletion type (p = .405), 104.8 ± 19.3 in boys and 102.6 ± 17.3 in girls (p = .293). The mean self‐care, mobility, and cognition scores were 47 (maximum 56), 33 (maximum 35), and 24 (maximum 35), respectively. All total scores and 18 subscores in the three functional domains were positively correlated with age (p < .05). Most children required assistance in problem‐solving, comprehension, and expression. The WeeFIM identified the strengths and limitations of children with PWS and confirmed that support and supervision were needed in cognitive and self‐care tasks.     

大豆异黄酮抑制大鼠前列腺增生及其作用机制

目的观察大豆异黄酮(SI)对良性前列腺增生(BPH)大鼠体内性激素、生长因子及细胞凋亡相关基因的影响,探讨SI对BPH的防治及作用机制。方法选择SPF级健康成年雄性SD大鼠100只,随机分为正常对照(NC)组、BPH模型组、低剂量[6 mg/(kg·d)]SI组、中剂量[12 mg/(kg·d)]SI组及高剂量[24 mg/(kg·d)]SI组,每组各20只。灌胃给药4周后麻醉处理大鼠,腹主动脉取血,制备血清;完整摘取大鼠前列腺组织。称重测定前列腺组织湿质量,计算前列腺指数(PI);酶联免疫吸附法(ELISA)测定大鼠血清雌二醇(E2)、睾酮(T)水平;免疫质印迹法(Western blotting)检测前列腺组织Fas、Fas L、Bax、Bcl-2、表皮生长因子(EGF)及其受体EGFR的表达。结果与NC组比,BPH组前列腺组织湿质量及PI均较明显增加(P<0.05);血清E2及T水平均显著升高(P<0.05);前列腺组织中Fas L、Bcl-2、EGF及EGFR表达水平均显著升高(P<0.05),而Fas和Bax表达水平均显著降低(P<0.05)。与BPH组比,中、高剂量SI组前列腺组织湿质量及PI均明显减少(P<0.05);血清E2及T水平均显著下降(P<0.05);前列腺组织中Fas L、Bcl-2、EGF及EGFR表达水平均显著降低(P<0.05),而Fas和Bax表达水平显著升高(P<0.05);其中,中剂量SI组各指标变化较低、高剂量组更显著(P<0.05)。结论 SI对BPH具有较好的抑制作用,其中中剂量SI作用效果更佳,其作用机制可能与调节机体性激素水平,下调生长因子及其受体表达以及调控细胞凋亡基因表达有关。     

Downregulating osteopontin reduces angiotensin II-induced inflammatory activation in vascular smooth muscle cells

Objective:  Atherosclerosis is considered as a chronic inflammatory response in arterial blood vessels. The function of osteopontin (OPN), a proinflammatory cytokine, in the Ang II-induced inflammatory activation in vascular smooth muscle cells (VSMCs) remains poorly understood. Methods:  In the present study, the role of OPN was investigated by knocking down OPN using small interfering RNA (siRNA). VSMCs from human saphenous vein were divided into three groups according to RNAi treatment: OPN siRNA group, sham (un-transfected) treated group, and control siRNA group. RNAi effect was investigated by real time PCR, western blotting analysis and ELISA. Then all groups were stimulated with Ang II. The inflammatory activation was assessed by determining the activation of NFκB and activator protein-1 (AP-1), and the release of interleukin-6 (IL-6) and IL-1β. Results:  OPN was knocked down effectively in OPN RNAi group. Inflammatory activations, such as NFκB and AP-1 activation and IL-6 accumulation, were induced by Ang II in sham treated group and control siRNA group. However, it was abolished in OPN siRNA group by the downregulation of OPN compared to sham treated group and control siRNA group. Conclusions:  This result suggested that OPN plays an important role in Ang II-induced inflammatory activation in VSMCs. The finding further supports OPN as a potential target for atherosclerotic therapy. Received 21 February 2008; returned for revision 6 May 2008; received from final revision 16 May 2008; accepted by S. Stimpson 21 August 2008 The first three authors contributed equally to this work.     

Sectional anatomy of the fetal brain in uterus at term on the sagittal plane

ObjectiveTo provide sectional anatomic data for the precise localization of developmental malformation of fetal brain in sagittal magnetic resonance imaging (MRI).MethodAfter abdominal and pelvic MRI scanning, the gravid specimen was cut into serial sagittal slices in correspondence with MRI in a low temperature laboratory to demonstrate the structures of fetal brain.Result(1) Directional determination of the sloping and rotating fetal head. From the serial sagittal sections of pregnant cadaver at term, we concluded that, the longitudinal lying and cephalic presentation fetal had run into maternal pelvis, and rotated and sloped to right. Anteroposterior position and median sagittal plane of the fetal was in correspondence with his mother’s. (2) Seven serial sagittal sections of the fetal brain were obtained through lateral surface of the right cerebral hemisphere, lateral sulcus, internal capsule, median sagittal plane, middle cerebellar peduncle, brainstem, and lateral surface of the left cerebral hemisphere.ConclusionThrough the comparison study between sagittal sections and corresponding MRI of fetal brain at term, we could obtain morphological anatomic structures and MRI of fetal brain, providing morphological demonstration of the intrauterine development of fetal brain and auxiliary diagnosis of ultrasound and MRI in pregnant woman.     

Increased expression of tuberin in human uterine leiomyoma

Female Eker rats harboring an insertional deletion in one copy of the tuberous sclerosis complex 2 (Tsc2) gene develop uterine leiomyoma, but the underlying mechanism of human uterine leiomyoma is not completely understood. To examine whether down-regulation of tuberin, a TSC2 gene product, is present in human uterine leiomyoma, we analyzed leiomyoma and matched myometrium tissues from 22 Chinese patients with Western blotting and real-time polymerase chain reaction analyses, and found that the expression of tuberin was significantly increased in leiomyoma tissues compared with matched myometrium tissues with inhibition of both the mammalian target of rapacmycin pathway and mitogen-activated protein kinase pathways.     

CA1 9-9、CA242和CA50联检对胰腺癌诊断的价值

目的：探讨联检肿瘤标志物CA19-9、CA242和CA50在胰腺癌诊断中的应用价值。方法：选择2007年1月～2008年10月湖南省人民医院门诊及住院患者共250人进行了CA19-9、CA242和CA50联检,其中120例为临床明确诊断的胰腺癌患者。结果：胰腺癌患者血清中的CA19-9、CA242和CA50水平明显高于对照组。CA19-9敏感性和特异性分别为82.0%和79.6%;CA242敏感性和特异性分别为78.5%和81.6%;CA50敏感性和特异性分别为52.7%和74.6%;联检CA19-9、CA242和CA50其敏感性和特异性提高为96.82%和98.75%。结论：采用CA19-9、CA242和CA50联检的方法,对胰腺癌的早期诊断具有一定的临床意义。     

左颞骨岩部囊实性占位

1.临床资料:患者男,25岁.因头晕、耳鸣、左耳听力下降5年于2005年9月8日入院手术.否认有头痛、发热、意识丧失、肢体抽搐等症状,无头颅外伤史.既往史、家族史无特殊.入院一般检查良好.神经系统检查:神志清,言语流畅,左耳传导性耳聋,四肢肌力、肌张力正常,未引出病理反射,感觉无异常.共济运动稳,Romberg征阴性.