棘突间动态稳定装置Coflex治疗退行性腰椎疾病的临床疗效分析

目的 探讨棘突间动态稳定装置Coflex治疗退行性腰椎疾病的临床疗效.方法 回顾性研究我院2009年1月至2013年12月采用Coflex治疗的173例退行性腰椎疾病患者.单纯Coflex治疗104例,男47例,女57例;年龄27～84岁,平均57.8岁;Topping-off治疗69例,男37例,女32例,年龄39～78岁,平均59.4岁.记录手术时间、术中出血量及术后并发症.选用Oswestry功能障碍指数(oswestry disability index,ODI)、视觉模拟评分(visual analoguescale,VAS)评价临床疗效.拍摄腰椎站立位的正侧位X片,测量并记录Coflex节段的术前、术后3个月、术后1年、终末随访时的椎间角度和椎体后缘高度.结果 本组随访12～64个月,平均(28.1±12.2)个月.单纯Coflex的平均手术时间(92.2±24.6)min,平均出血量(195.5±62.2) ml;Topping-off的平均手术时间(173.7±28.7)min,平均出血量(415.5±80.7)ml.单纯Coflex术后伤口感染2例,术后5年翻修1例;Topping-off术后伤口感染2例,椎管内血肿2例,术后3年Coflex置入节段翻修1例,术后3年融合节段下位椎间盘突出行二次手术l例.术后1年随访的腰痛及腿痛VAS评分、ODI评分与术前比较,差异有统计学意义(P＜0.05).Coflex置入节段术后3个月椎间角度均小于术前,差异均有统计学意义(P＜0.05),术后1年、终末椎间角度与术前比较差异均无统计学意义(P＞0.05);术后3个月椎体后缘高度均大于术前,差异有统计学意义(P＜0.05),术后1年、终末椎体后缘高度与术前比较差异无统计学意义(P＞0.05).结论 棘突间动态稳定装置Coflex治疗退行性腰椎疾病的中短期随访临床疗效满意,Coflex节段的椎间角度及椎体后缘高度术后短期内可获得明显的改善.     

The Effects of a Ketogenic Diet on Patients with Dihydrolipoamide Dehydrogenase Deficiency

Background: Dihydrolipoamide dehydrogenase (DLD lipoamide dehydrogenase, the E3 subunit of the pyruvate dehydrogenase complex (PDHC)) is the third catalytic enzyme of the PDHC, which converts pyruvate to acetyl-CoA catalyzed with the introduction of acetyl-CoA to the tricyclic acid (TCA) cycle. In humans, PDHC plays an important role in maintaining glycose homeostasis in an aerobic, energy-generating process. Inherited DLD-E3 deficiency, caused by the pathogenic variants in DLD, leads to variable presentations and courses of illness, ranging from myopathy, recurrent episodes of liver disease and vomiting, to Leigh disease and early death. Currently, there is no consensus on treatment guidelines, although one suggested solution is a ketogenic diet (KD). Objective: To describe the use and effects of KD in patients with DLD-E3 deficiency, compared to the standard treatment. Results: Sixteen patients were included. Of these, eight were from a historical cohort, and of the other eight, four were on a partial KD. All patients were homozygous for the D479V (or D444V, which corresponds to the mutated mature protein without the mitochondrial targeting sequence) pathogenic variant in DLD. The treatment with partial KD was found to improve patient survival. However, compared to a historical cohort, the patients’ quality of life (QOL) was not significantly improved. Conclusions: The use of KD offers an advantage regarding survival; however, there is no significant improvement in QOL.     

In vitro Investigation of Cytotoxic and Apoptotic Effects of Cynara L. Species in Colorectal Cancer Cells

Apoptotic and cytotoxic activity of plant extracts obtaining from naturally growing Cynara syriaca in Turkeyand cultivated C cardunculus against DLD1 colorectal cancer cells was determined. Extracts from wild andcultivated Cynara species were obtained from their vegetative parts and receptacles using hexane and applied withfive different dose (0.1-1 mg/ml) as well as apigenin for MTT tests for three time periods (24, 48 and 72 hours).After cells were treated with IC50 doses for each extract total DNA and RNA were isolated for determination ofthe cause of cell death. From isolated RNAs, cDNA were synthesized and amplification of p21, BCL-2 and BAXgene regions was carried out. Consequently, we found that pro-apoptotic (BAX) gene expression and a cell cycleinhibitor (p21) were induced in the presence of our artichoke extracts. In contrast, anti-apoptotic BCL-2 geneexpression was reduced compared to the control group. In addition DNA fragmentation results demonstratedDLD1 cell death via apoptosis.     

靶向铜死亡相关基因治疗类风湿关节炎生物信息学分析及干预中药的预测

目的 探索铜死亡相关基因在类风湿关节炎（rheumatoid arthritis,RA）中的表达及其作用机制,并筛选通过靶向铜死亡基因治疗RA的潜在中药。方法 通过检索GEO数据库获得RA芯片数据,分析铜死亡基因在RA中表达水平;依据铜死亡基因表达情况构建高表达亚型和低表达亚型,并进行差异分析,筛选出与RA相关的铜死亡基因。按不同分组对基因表达矩阵进行免疫浸润分析,并分析免疫浸润细胞与铜死亡基因之间的相关性。利用Kobas在线工具对差异基因进行京都基因与基因组百科全书（Kyoto encyclopedia of genes and genomes,KEGG）通路富集分析。通过Herb数据库检索靶向铜死亡基因治疗RA的潜在中药及其有效成分,使用Autodock vina软件模拟药物与铜死亡靶蛋白结合活性。通过收集临床样本验证铜死亡相关基因在RA中表达水平。结果 FDX1、DLD、DLAT、LIAS、GLS、LIPT1和PDHB 7个铜死亡相关基因在RA中差异表达。免疫浸润分析结果显示,在RA中活化的记忆CD4⁺ T细胞、静息自然杀伤（natural killer,NK）细胞和中性粒细胞与铜死亡相关。富集分析结果显示,铜死亡主要与趋化因子信号通路、Toll样受体信号通路、白细胞介素-17（interleukin-17,IL-17）信号通路、肿瘤坏死因子信号通路、核因子-κB信号通路、p53信号通路和过氧化物酶体增殖物激活受体信号通路相关。虎杖叶可能是靶向铜死亡基因治疗RA的潜在中药。分子对接结果显示,虎杖叶有效成分均有与铜死亡靶蛋白结合的可能。DLD、GLS、FDX1、DLAT在RA患者外周血单个核细胞中mRNA表达水平升高。结论 铜死亡相关基因表达水平与RA病程进展相关,并预测虎杖叶是潜在靶向铜死亡基因治疗RA的药物,为RA的临床诊疗及药物开发提供了新的方向和理论基础。     

A novel mutation in the dihydrolipoamide dehydrogenase E3 subunit gene (DLD) resulting in an atypical form of alpha-ketoglutarate dehydrogenase deficiency

The alpha-ketoglutarate dehydrogenase complex (KGDC) catalyses the decarboxylation of alpha-ketoglutarate into succinyl-coenzyme A in the Krebs cycle. This enzymatic complex is made up of three subunits (E1, encoded by PDHA1; E2, encoded by DLST; and E3, encoded by DLD). The E3 subunit is common to two other enzymatic complexes, namely pyruvate dehydrogenase complex (PDC) and branched-chain ketoacid dehydrogenase complex (BCKDC). KGDC deficiency is a rare autosomal recessive disorder, most often presenting with severe encephalopathy and hyperlactatemia with neonatal onset. We found a KGDC deficiency in cultured skin fibroblasts from three siblings born to consanguinous parents. E3 subunit activity was shown to be deficient (20% of control values), despite the absence of usual clinical clues to E3 deficiency, i.e. accumulation of pyruvate and branched-chain amino acids in plasma and branched-chain alpha-ketoacids in urine. RT-PCR of E3 mRNA from the three patients, followed by sequencing, revealed an homozygous c.1444A>G substitution located in E3 exon 13, predictive of a p.R482G (or R447G in the processed gene product) substitution in a highly conserved domain of the protein. Only eleven E3 mutations have been reported so far. The only other case of E3 deficiency without clinical or biochemical evidences of PDC and BCKDC deficiencies has been ascribed to a c.1436A>T (p.D479V; or D444V in the processed gene product) mutation, very close to the mutation reported herein. Since c.1444A>G (p.R482G; or R447G in the processed gene product) and c.1436A>T (p.D479V; or D444V in the processed gene product) lie within the interface domain of E3 with E2 (KGDC and BCKDC) or the E3-binding protein (PDC), our data suggest that interaction of E3 with these other subunits differs in some extent among KGDC, PDC, and BCKDC.     

发育性语言障碍儿童的亲子互动特征及影响因素分析

目的 研究发育性语言障碍(DLD)儿童亲子互动的特征以及影响因素,为临床早期发现、早期干预提供依据.方法 选取2018年1月-2020年3月在山东大学齐鲁医院儿童保健门诊就医,经专业医师确诊的DLD儿童30例,另选取同时期在山东大学齐鲁医院儿童保健门诊及山东大学中心校区校医院儿童保健门诊进行健康查体的正常儿童30例为对...     

Thermal and Mechanical Variation Analysis on Multi-Layer Thin Wall during Continuous Laser Deposition,Continuous Pulsed Laser Deposition,and Interval Pulsed Laser Deposition

Direct laser deposition (DLD) is widely used in precision manufacturing, but the process parameters (e.g., laser power, scanning patterns) easily lead to changes in dimensional accuracy and structural properties. Many methods have been proposed to analyze the principle of distortion and residual stress generation, but it is difficult to evaluate the involvement of temperature and stress in the process of rapid melting and solidification. In this paper, a three-dimensional finite element model is established based on thermal–mechanical relationships in multilayer DLD. Differences in temperature and residual stress between continuous laser deposition (CLD) and pulsed laser deposition (PLD) are compared with the numerical model. To validate the relationship, the temperature and residual stress values obtained by numerical simulation are compared with the values obtained by the HIOKI-LR8431 temperature logger and the Pulstec μ-X360s X-ray diffraction (XRD) instrument. The results indicate that the temperature and residual stress of the deposition part can be evaluated by the proposed simulation model. The proposed PLD process, which includes continuous pulsed laser deposition (CPLD) and interval pulsed laser deposition (IPLD), were found more effective to improve the homogeneity of temperature and residual stress than the CLD process. This study is expected to be useful in the distortion control and microstructure consistency of multilayer deposited parts.     

Identification of DLD,by immunoproteomic analysis and evaluation as a potential vaccine antigen against three Vibrio species in Epinephelus coioides

Vibrio spp. represent a serious threat to the culture of Epinephelus coioides (Orange-spotted Grouper) in Southeast Asia. In this study we used two-dimensional electrophoresis (2-DE) and Western blotting to identify common immunogenic proteins of Vibrio alginolyticus, Vibrio harveyi and Vibrio parahaemolyticus. Membranes were probed with orange-spotted grouper anti-V. alginolyticus sera and accordingly 60, 58 and 48 immunogenic protein spots were detected. By matching analysis for the three Western blotting membranes, 6 cross immunogenic spots for the three Vibrio species were identified. They were Outer membrane protein W (OmpW), dihydrolipoamide dehydrogenase (DLD), succinate dehydrogenase flavoprotein subunit(SDHA), elongation factor Ts(Ts), peptide ABC transporter periplasmic peptide-binding protein and phosphoenolpyruvate carboxykinase(PEPCK). One of the proteins, DLD, was used to evaluate the cross protective function for E. coioides with a bacterial immunization and challenge method. The relative percent survival rate of E. coioides against V. alginolyticus, V. harveyi and V. parahaemolyticus was 90%, 86% and 80%, respectively. This work may provide potential cross protective vaccine candidate antigens for three Vibrio species, and DLD may be considered as an effective cross-protective immunogen against three Vibrio species.