钙离子通道蛋白TRPV6及其相关疾病的研究进展

瞬时受体电位亚家族V成员6 (Transient Receptor Potential Channel Subfamily V Member 6, TRPV6) 是一种钙离子高度选择性离子通道，在多种组织中均有表达，控制细胞顶端钙离子的进入，在维持钙稳态中发挥重要作用。TRPV6功能异常会影响体内钙稳态，进而引发新生儿骨骼发育异常、甲状旁腺功能亢进、骨与软骨代谢异常、肾结石和高尿钙症、 以及炎症性肠病和慢性胰腺炎等多种疾病。近年来研究也表明，TRPV6的上调与多种肿瘤的侵袭性增加有关，具有作为肿瘤检测的标志物以及治疗靶点的潜力。本综述将聚焦于TRPV6与其在相关疾病中发挥的作用，旨在为TRPV6作为药物靶点实现临床转化提供理论依据。     

动物瘢痕模型的相关研究进展

皮肤损伤后的异常愈合会导致病理性瘢痕的产生。病理性瘢痕的出现不仅影响美观,严重时还会造成心理和生理功能障碍。病理性瘢痕的机制研究对于瘢痕治疗有极为重要的意义。其中,动物瘢痕模型是目前研究病理性瘢痕的重要模型手段之一。理想的动物瘢痕模型应该在组织学、细胞学等层面尽可能接近于人类的病理性瘢痕。该文分别从传统技术动物瘢痕中的啮齿类动物模型、兔耳模型和猪模型,以及新技术动物瘢痕模型这两个方面,结合近年来在瘢痕领域应用较多的研究,进行了相应系统的阐述。     

同型半胱氨酸对高血压患者脑卒中复发风险的影响

目的探讨高血压合并脑卒中患者的血浆同型半胱氨酸（Hcy）水平与其他危险因素对于脑卒中复发的影响。 方法分析徐州市中心医院心内科和徐州医科大学附属医院神经外科自2012年5月至2013年12月收治的1623例高血压脑卒中患者的基线资料，中位随访4.9年，根据随访事件中是否发生脑卒中分为复发组（312例）与未复发组（1311例）。Kaplan-Meier生存分析比较不同危险因素脑卒中复发率的差异，单因素与多因素Cox回归模型分析影响脑卒中复发的独立危险因素，以及危险因素之间的交互作用。 结果复发组年龄、空腹血糖、Lg Hcy的水平，以及糖尿病、房颤的患病率均高于未复发组（P<0.05）。Kaplan-Meier生存分析显示，糖尿病、房颤、年龄≥60岁、空腹血糖≥7.0 mmol/L、Hcy≥15 μmol/L的脑卒中复发率明显升高（Log-rank检验，P<0.05）。多因素Cox回归模型分析显示，高龄、Lg Hcy水平升高，以及房颤、糖尿病是脑卒中复发的独立危险因素。Lg Hcy分别与糖尿病、空腹血糖、年龄存在交互作用。 结论血浆Hcy水平升高既是高血压合并脑卒中患者卒中复发的独立危险因素，又通过与糖尿病、高龄、空腹血糖水平升高的交互作用显著增加脑卒中复发风险。     

HIFα Regulates Developmental Myelination Independent of Autocrine Wnt Signaling

The developing CNS is exposed to physiological hypoxia, under which hypoxia-inducible factor α (HIFα) is stabilized and plays a crucial role in regulating neural development. The cellular and molecular mechanisms of HIFα in developmental myelination remain incompletely understood. A previous concept proposes that HIFα regulates CNS developmental myelination by activating the autocrine Wnt/β-catenin signaling in oligodendrocyte progenitor cells (OPCs). Here, by analyzing a battery of genetic mice of both sexes, we presented in vivo evidence supporting an alternative understanding of oligodendroglial HIFα-regulated developmental myelination. At the cellular level, we found that HIFα was required for developmental myelination by transiently controlling upstream OPC differentiation but not downstream oligodendrocyte maturation and that HIFα dysregulation in OPCs but not oligodendrocytes disturbed normal developmental myelination. We demonstrated that HIFα played a minor, if any, role in regulating canonical Wnt signaling in the oligodendroglial lineage or in the CNS. At the molecular level, blocking autocrine Wnt signaling did not affect HIFα-regulated OPC differentiation and myelination. We further identified HIFα–Sox9 regulatory axis as an underlying molecular mechanism in HIFα-regulated OPC differentiation. Our findings support a concept shift in our mechanistic understanding of HIFα-regulated CNS myelination from the previous Wnt-dependent view to a Wnt-independent one and unveil a previously unappreciated HIFα–Sox9 pathway in regulating OPC differentiation.SIGNIFICANCE STATEMENT Promoting disturbed developmental myelination is a promising option in treating diffuse white matter injury, previously called periventricular leukomalacia, a major form of brain injury affecting premature infants. In the developing CNS, hypoxia-inducible factor α (HIFα) is a key regulator that adapts neural cells to physiological and pathologic hypoxic cues. The role and mechanism of HIFα in oligodendroglial myelination, which is severely disturbed in preterm infants affected with diffuse white matter injury, is incompletely understood. Our findings presented here represent a concept shift in our mechanistic understanding of HIFα-regulated developmental myelination and suggest the potential of intervening with an oligodendroglial HIFα-mediated signaling pathway to mitigate disturbed myelination in premature white matter injury.     

儿童慢性乙型肝炎细胞免疫功能及胸腺素疗效

目的　探讨慢性乙型肝炎(CHB)患儿细胞免疫功能及胸腺素疗效。方法　6 0例CHB患儿随机分为常规组(予常规治疗)和胸腺素组(在常规治疗基础上+胸腺素) ,并以6 0例健康儿童作为正常对照组。于治疗前、疗程结束后1mo检测T细胞亚群(CD+ 3 、CD+ 4 、CD+ 8)、血清白细胞介素2 (IL 2 )及可溶性白细胞介素2受体(sIL 2R)水平;定期复查肝功能、乙肝标志物和HBV DNA。结果　与正常对照组比较,CHB组CD+ 3 与CD+ 4 的百分率、CD+ 4 /CD+ 8及血清IL 2水平明显降低(P均<0 0 1) ,CD+ 8百分率及血清sIL 2R水平明显升高(P均<0 0 1) ;与常规组比较,胸腺素组血清ALT明显下降(P <0 0 1) ,ALT复常时间明显缩短(P <0 0 1) ,HBeAg转阴率明显上升(P <0 0 5 ) ,各免疫学指标明显恢复,差异均有统计学意义(P <0 0 1或P <0 0 5 )。结论　CHB患儿细胞免疫功能低下,胸腺素能增强细胞免疫功能,有利于病毒清除和肝功能的恢复     

联合应用经腹腹膜前腹腔镜疝修补术和腹腔内网片植入术治疗成人腹股沟疝

目的联合应用经腹腹膜前腹腔镜疝修补术(transabdominal preperitoneal prosthetic,TAPP)和腹腔内网片植入术(intraperitoneal onlay mesh,IPOM),探讨理想的腹腔镜下腹股沟疝修补的方法。方法2006年1月~12月,对30例成人腹股沟疝行腹腔镜下修补。以腹壁下血管内侧缘为界,把疝薄弱区纵行分成内侧和外侧,内侧采用改进的TAPP方法,外侧仍用IPOM方法。沿腹壁下血管内侧缘纵行剪开腹膜后向内侧游离的区域内基本上是无血管区,亦无重要的神经,组织疏松极易游离,数分钟内即可分离出所需要的面积(7.5 cm×6.5 cm)。补片的材料亦分为内侧和外侧,内侧是聚丙烯材料,外侧应用Proceed补片。结果30例均在硬膜外麻醉下完成,手术时间单侧30~40 min,平均35 min,双侧50~60 min,平均55min,术中出血1~5 ml,术后第2天可离床活动,术后3~4天出院,术后2周均恢复工作。术后随访2~12个月,平均9个月,无粘连性肠梗阻,腹股沟部和全身无不良反应。结论联合应用TAPP和IPOM后,能体现微创的原则,易掌握,损伤少,手术时间短,恢复快,手术效果确切。     

Characteristics of the Nonselective Cation Current （NSCCs） in Rabbit Left Ventricular Epicardial, Midmyocardial and Endocardial Myocytes

Objectives Recent studies have described regional differences in the electrophysiology and pharmacology of ventricular myocardium in canine, feline, rat, guinea pig, and human hearts. This has been shown to be due to a smaller IKs and a lager sodium-calcium exchange current (INa-Ca) and late INa in M region (deep subepicardial to midmyocardial). Studies from our laboratory have found a new repolarization current-nonselective cation current (NSCCs) existing in rabbit right ventricular myocytes. Methods We examined the characteristics of NSCCs in epicardial, M region, and endocardial cells isolated from the rabbit left ventricle with standard microelectrode and whole-cell patch-clamp techniques. The permeability to Na , K , Li , Cs but not to Cl- indicating that it was a nonselective cation current. Gd3 (0.1 mmol/l) and La3 (0.1 mmol/l) can block the current markedly. Results Further characterization of NSCCs was significantly smaller in M cells than in epicardial and endocardial cells. NSCCs current density was significantly smaller in M cells than in epicardial and endocardial cells. With repolarization to -80 mV, INs current density was (-0.44±0.05) PA/PF in endocardial cells, (-0.12±0.05) PA/PF in M cells and (-0.28±0.07) PA/PF in epicardial cells; and with repolarization to 30 mV, INs current density was (1.09±0.29) PA/PF in endocardial cells, (0.38±0.09) PA/PF in M cells and (0.91±0.32) PA/PF in epicardial cells. Conclusions Transmural dispersion of repolarization was due to the heterogeneity of NSCCs in rabbit left ventricle epicardial, endocardial myocytes and M cells. These findings may advance our understanding of the ionic basis for our understanding of factors contributing to the development of cardiac arrhythmias.     

内蒙古地区食管癌组织中人乳头瘤病毒的检测

目的:了解内蒙古地区HPV感染与食管癌的关系,探讨HPV在食管癌病因学中的作用.方法:应用通用引物PCR法检测食管癌标本中HPV DNA.结果:在来自内蒙古地区41例食管癌标本中,HPV DNA检出率为零.结论:内蒙古地区食管癌发生可能与HPV感染无关.     

胃癌累及胰腺的外科治疗与预后(附120例报告)

目的探讨胃癌累及胰腺的外科治疗方法与预后的关系。方法回顾性分析我院1984年6月～2003年10月手术治疗累及胰腺的胃癌120例。结果本组120例中,根治切除组41例,姑息切除组23例,未切除组56例。根治组41例中经病理证实胰腺有癌细胞浸润者30例,占73.2%,淋巴结转移率为85.4%。其中No10、11淋巴结转移率为73.1%。术后102例得到随访,随访率为85%,1、3、5年的生存率分别为:根治切除组为73%、37%、17%,姑息切除组为22%、9%、4%,未切除组为9%、2%、0%。根治切除组1,3年生存率明显高于姑息性切除组和未切除组(P<0.05),5年生存率明显高于未切除组(P<0.01),但与姑息性切除组无显著性差异。姑息性切除组和未切除组1、3年生存率无显著性差异,但5年生存率明显高于未切除组(P<0.01)。结论胃癌累及胰腺的根治切除可提高1,3年生存率,选择合适的适应征是关键。姑息切除有助于改善生存质量,对改善预后意义不大。     

膀胱癌组织形态定量分析和病理学研究：附20例报告

对２０例膀胱移行上皮癌大切片ＨＥ染色，观察肿瘤表面、基部，浸润深部的组织形态特征，运用ＡｇＮＯＲ银染技术和图像分析技术进行了ＡｇＮＯＲ颗粒计数和核形态计量研究。结果表明：膀胱移行上皮癌表面组织与基部组织的分级和恶性程度无显著性差异。肿瘤浸润深部的组织分级与恶性程度比肿瘤表面组织的高。