异补骨脂素促进大鼠骨髓间充质干细胞向成骨细胞分化并抑制其向脂肪细胞分化

目的:研究异补骨脂素是否影响骨髓间充质干细胞向成骨细胞和脂肪细胞分化的能力.方法:不同浓度异补骨脂素分别处理在成骨或成脂诱导培养液中培养的大鼠骨髓问充质干细胞(bone marrow mesenchymal stem cells,BM-MSCs),培养14天,分别行哑甲基蓝、碱性磷酸酶(alkaline phospha...     

单侧椎弓根螺钉联合对侧经椎板关节突螺钉内固定与双侧椎弓根螺钉内固定治疗腰椎退行性疾病疗效的Meta分析

目的 :通过Meta分析评价后路减压融合单侧椎弓根螺钉联合对侧经椎板关节突螺钉(unilateral pedicle screws plus contralateral translaminar facet screws,UPSFS)内固定与双侧椎弓根螺钉(bilateral pedicle screws,BPS)内固定治疗腰椎退行性疾病的疗效。方法:检索PubMed、Cochrane、Embase、CNKI、万方、维普数据库自建库至2021年1月发表的关于后路减压融合UPSFS内固定与BPS内固定治疗腰椎退行性疾病的病例对照研究,按照纳入排除标准进行文献筛选,采用纽卡斯尔-渥太华量表(Newcastle-Ottawa scale,NOS)对纳入研究进行质量评价,提取纳入研究结局指标数据,包括术前与末次随访腰痛和腿痛视觉模拟评分(visual analogue scale,VAS)、日本骨科协会(JOA)评分、Owestry功能障碍指数(ODI)、手术节段椎间隙高度的改变值,手术切口长度、手术时间、术中出血量、术后引流量、住院费用,末次随访时手术节段融合率以及并发症发生率,提取数据后通过Review Manager 5.3软件进行Meta分析。结果:共纳入10篇文献,所有研究NOS评价均符合要求。总计有588例患者接受了内固定手术,其中UPSFS固定291例,BPS固定297例,随访时间12～60个月。Meta分析结果显示,术前与末次随访时腿痛VAS评分改变值[加权均数差(weighted mean difference,WMD)=-0.30,95%置信区间(confidence interval,CI)(-0.57,-0.03)]、切口长度[WMD=-4.49,95%CI(-6.64,2.55)]、手术时间[WMD=-32.61,95%CI (-45.23,19.99)]、术中出血量[WMD=-152.63,95%CI (-208.91,-96.35)]、术后引流量[WMD=著性差异,UPSFS组优于BPS组(P0.05);而术前与末次随访腰痛VAS评分[WMD=-0.00,95%CI(-0.26,0.27)]、JOA评分[WMD=0.26,95%CI(-1.59,2.11)]、ODI[WMD=0.26,95%CI(-1.59,2.11)]、手术节段椎间隙高度[WMD=0.01,95%CI(-0.61,0.63)]的改变值,末次随访时的融合率[OR=0.31,95%CI(0.10,1.03)]以及并发症发生率[OR=1.43,95%CI(0.60,3.40)],两组之间均无显著性差异(P0.05)。结论:在后路减压融合手术治疗腰椎退行性疾病时,UPSFS固定具有和BPS固定相当的临床疗效和安全性,且前者对患者腿痛程度的改善更加显著,同时可以缩小手术切口,减少手术时间、术中出血量、术后引流量以及住院费用。     

The ClinGen Brain Malformation Variant Curation Expert Panel: Rules for somatic variants in AKT3, MTOR,PIK3CA,and PIK3R2

PurposePostzygotic (somatic) variants in the mTOR pathway genes cause a spectrum of distinct developmental abnormalities. Accurate classification of somatic variants in this group of disorders is crucial for affected individuals and their families.MethodsThe ClinGen Brain Malformation Variant Curation Expert Panel was formed to curate somatic variants associated with developmental brain malformations. We selected the genes AKT3, MTOR, PIK3CA, and PIK3R2 as the first set of genes to provide additional specifications to the 2015 American College of Medical Genetics and Genomics/Association for Molecular Pathology (ACMG/AMP) sequence variant interpretation guidelines, which currently focus solely on germline variants.ResultsA total of 24 of the original 28 ACMG/AMP criteria required modification. Several modifications used could be applied to other genes and disorders in which somatic variants play a role: 1) using variant allele fraction differences as evidence that somatic mutagenesis occurred as a proxy for de novo variation, 2) incorporating both somatic and germline evidence, and 3) delineating phenotype on the basis of variable tissue expression.ConclusionWe have established a framework for rigorous interpretation of somatic mosaic variants, addressing issues unique to somatic variants that will be applicable to many genes and conditions.