Transforming growth factor-beta induces the expression of ANF and hypertrophic growth in cultured cardiomyoblast cells through ZAK

Transforming growth factor-beta (TGF-beta) has been associated with the onset of cardiac cell hypertrophy, but the mechanisms underlying this dissociation are not completely understood. By a previous study, we investigated the involvement of a MAP3K, ZAK, which in cultured H9c2 cardiac cells is a positive mediator of cell hypertrophy. Our results showed that expression of a dominant-negative form of ZAK inhibited the characteristic TGF-beta-induced features of cardiac hypertrophy, including increased cell size, elevated expression of atrial natriuretic factor (ANF), and increased organization of actin fibers. Furthermore, dominant-negative MKK7 effectively blocked both TGF-beta-and ZAK-induced ANF expression. In contrast, a JNK/SAPK specific inhibitor, sp600125, had little effect on TGF-beta- or ZAK-induced ANF expression. Our findings suggest that a ZAK mediates TGF-beta-induced cardiac hypertrophic growth via a novel TGF-beta signaling pathway that can be summarized as TGF-beta>ZAK>MKK7>ANF.     

595nm 激光对兔耳瘢痕成纤维细胞增殖活性的影响

目的：探讨兔耳增生性瘢痕动物模型形成过程中成纤维细胞增殖活性的动态变化及595nm Vbeam激光照射的影响。方法：利用兔耳腹侧面建立增生性瘢痕模型,按不同时间段取材,采用免疫组织化学方法观察瘢痕形成不同时期增殖细胞核抗原（PCNA）蛋白的表达,对比研究在兔耳增生性瘢痕形成过程中595nm Vbeam激光照射对成纤维细胞增殖活性的影响。结果：上皮化后增殖细胞核抗原阳性细胞反应率随时间推移逐渐增高,至上皮化后4周达高峰。从上皮化后1周开始即可见到595nm Vbeam激光照射后增殖细胞核抗原蛋白表达较对照组明显减弱,成纤维细胞增殖活性受到明显抑制,两组差异具有极显著性（P〈0．01）。结论：595nm Vbeam激光照射可明显抑制兔耳增生性瘢痕成纤维细胞的增殖活性,对兔耳腹侧面增生性瘢痕有明显的防治作用。     

关节镜清理术治疗前踝撞击征的疗效

目的:探讨踝关节镜对前踝撞击征的诊疗价值。方法:采用关节镜清理术治疗前踝撞击综合征33例,其中男23例,女10例。年龄平均39岁(18～72岁)。左踝16例,右踝17例。病史6个月至20年,有运动损伤史13例,踝关节扭伤病史17例,踝关节骨折史3例。临床表现为踝关节肿胀、疼痛和下蹲活动受限。X线片显示胫骨前唇和距骨骨质增生,MRI显示距骨软骨损伤,踝关节腔内积液。采用局麻关节镜下骨赘磨削,滑膜切除,踝关节清理术。结果:随访33例,平均时间35个月(4个月-6年)。术后踝关节背伸活动功能正常,按照McGuire踝关节评分系统对术前、术后踝关节功能进行评估,术前平均55分,术后平均80分,术后提高了25分。优13例,良15例,可3例,差2例,优良率84.8%。结论:局麻下踝关节镜骨赘切除、滑膜刨削和软骨修整可有效解除踝关节撞击症状,手术创伤小、功能恢复快,效果满意。     

家族性肥厚型心肌病一家系的调查分析

目的:分析一家族性肥厚型心肌病的特点。方法:对我院就诊的一肥厚型心肌病大家系进行临床调查研究,分析其临床特点,绘制家系图谱。结果:该家系为连续四代遗传,家系成员共35例,患者11例,猝死3例,死亡2例。有1例患者房颤及脑梗塞,2例患者行永久性起搏器植入术,猝死年龄最小3岁,符合肥厚型心肌病高发病率、高猝死率、发病年龄早等特点。结论:家族性肥厚型心肌病详细的家系调查有助于了解疾病全貌,更好地揭示其遗传规律。     

速度向量成像技术对肥厚型心肌病左心室扭转功能和收缩功能的影响

摘要 目的：研究速度向量成像技术对肥厚型心肌病（HCM）左心室扭转功能和收缩功能的影响。方法：纳入我院从2018年1月～2019年1月收治的HCM患者30例进行研究,记作病变组,另取同期于我院进行体检的健康志愿者30例作为对照组。比较两组常规左心功能超声心动图指标、左室整体扭转和解旋运动指标、左室局部扭转和解旋运动指标、圆周应变以及应变率。结果：病变组舒张末期容积（EDV）、收缩末期容积（ESV）、每搏量（SV）均较对照组更低（P＜0.05）,而两组左室射血分数（LVEF）比较差异不显著（P＞0.05）。病变组心内膜的左心室扭转角度（LVtw）以及左心室扭矩（LVtor）均显著高于对照组,而心内膜及心外膜解扭转率（UntwR）显著低于对照组（P＜0.05）。病变组基底部心内膜旋转速率、心尖部心外膜旋转速率均显著低于对照组,心尖部心内膜旋转速率显著高于对照组,心尖部心外膜解旋速率显著高于对照组（P＜0.05）。病变组基底部心内膜圆周应变低于对照组,基底部、心尖部心外膜圆周应变高于对照组（P＜0.05）;病变组基底部、心尖部心外膜应变率均高于对照组（P＜0.05）。结论：HCM患者收缩功能降低,且局部心肌圆周方向的形变能力明显下降。     

Aggrecan modulation of growth plate morphogenesis

Chick and mouse embryos with heritable deficiencies of aggrecan exhibit severe dwarfism and premature death, demonstrating the essential involvement of aggrecan in development. The aggrecan-deficient nanomelic (nm) chick mutant E12 fully formed growth plate (GP) is devoid of matrix and exhibits markedly altered cytoarchitecture, proliferative capacity, and degree of cell death. While differentiation of chondroblasts to pre-hypertrophic chondrocytes (IHH expression) is normal up to E6, the extended periosteum expression pattern of PTCH (a downstream effector of IHH) indicates altered propagation of IHH signaling, as well as accelerated down-regulation of FGFR3 expression, decreased BrdU incorporation and higher levels of ERK phosphorylation, all indicating early effects on FGF signaling. By E7 reduced IHH expression and premature expression of COL10A1 foreshadow the acceleration of hypertrophy observed at E12. By E8, exacerbated co-expression of IHH and COL10A1 lead to delayed separation and establishment of the two GPs in each element. By E9, increased numbers of cells express P-SMAD1/5/8, indicating altered BMP signaling. These results indicate that the IHH, FGF and BMP signaling pathways are altered from the very beginning of GP formation in the absence of aggrecan, thereby inducing premature hypertrophic chondrocyte maturation, leading to the nanomelic long bone growth disorder.     

Termination of Ventricular Tachycardia with Antitachycardia Pacing after Ineffective Shock Therapy in an ICD Recipient with Hypertrophic Cardiomyopathy

Implantable Cardioverter Defibrillator (ICD) implantation is the only established therapy for primary or secondary prevention of sudden cardiac death in patients with Hypertrophic Cardiomyopathy (HCM). Ineffectiveness of shock therapy for the termination of potentially fatal ventricular arrhythmias in ICD recipients is rare in the presence of appropriate arrhythmia detection by the device. We report the case of a 48-year-old woman with HCM and a single chamber ICD, who received five inefficient high-energy (35 Joules) shocks for the termination of an appropriately detected episode of Ventricular Tachycardia (VT). The episode was safely terminated with a subsequent application of Antitachycardia Pacing (ATP) by the device. At the following ICD control, an acceptable defibrillation threshold was detected.     

Molecular differentiation in epiphyseal and physeal cartilage. Prominent role for gremlin in maintaining hypertrophic chondrocytes in epiphyseal cartilage

We have studied hypertrophic and immediately adjacent pre-hypertrophic chondrocytes at the same stage of histologic development in 7 day old post-natal Balb/C mouse physes and epiphyses. Laser capture microdissection (LCM) and GeneChip microarray analysis compared the molecular composition of the two hypertrophic chondrocyte regions. Molecules upregulated in dramatically higher levels in the epiphysis were gremlin (58-fold), epidermal growth factor-containing fibulin-like extracellular matrix protein 1 (25-fold), and frizzled related protein (6.4-fold and 5.7-fold). Molecules upregulated in higher levels in the physis were proline arginine-rich end leucine-rich repeat protein (PRELP) (15.6-fold), pyrophosphatase (inorganic) 1 (10-fold) and hedgehog-interacting protein (7.3-fold). Immunocytochemistry for gremlin confirmed specific localization patterns. This study indicates a critical site-specific role for hypertrophic chondrocytes with different synthesis patterns in separate regions even though they appear structurally the same and are at the same stage of development.