阻塞性睡眠呼吸暂停低通气综合征患者CYP3A4基因多态性的检测

目的探讨阻塞性睡眠呼吸暂停低通气综合征(OSAHS)CYP3A4基因的多态性,了解其对芬太尼类药物的敏感性及不同基因型的人群分布特征,指导临床个体化用药。方法对50例OSAHS患者进行CYP3A4基因的多态性检测,采静脉血,通过DNA抽提-PCR扩增-焦磷酸测序方法检测CYP3A4基因。结果野生纯合型型34例(68%),突变杂合型15例(30%),突变纯合型型1例(2%)。结论OSAHS患者中约2%为AA型,该型对芬太尼类药物极其敏感,术后有易发生窒息的风险,应高度警惕芬太尼类药物呼吸抑制的潜在风险。     

经9次核酸检测终确诊的新型冠状病毒肺炎患者1例分析

目前新型冠状病毒肺炎(COVID-19)疫情在全球蔓延,形势严峻,并对全球公共卫生事业构成巨大挑战,快速准确的诊断COVID-19对疫情的防控有重要意义。本文报道1例COVID-19患者的调查和确诊过程,以对COVID-19确诊和疫情防控提供有价值的参考。患者为赴渝务工于2020年1月23日返乡人员,在渝期间,其同工地的一同事确诊为COVID-19,之后该工地接连有另外8位同事被确诊。患者返乡后2月2日被当地疫情防控单位采取医学隔离。患者于隔离后不久出现咳嗽,阵发性,干咳为主,偶可咳出黄色痰液等COVID-19相关临床症状,遂被当地新型冠状病毒肺炎定点医疗单位收治,后经市级新型冠状病毒肺炎诊治专家组远程视频会诊转入四川大学华西医院资阳医院。患者先后经历9次核酸检测,在前8次核酸检测均为阴性的情况下,于第9次核酸检测结果为阳性,2月21日最终确诊为新型冠状病毒肺炎。     

基于灰色关联度分析和聚类分析的3种滇产重楼抗肝癌作用谱效关系探索

目的:研究长柱重楼、滇重楼和南重楼的HPLC指纹图谱与其抗肝癌作用的谱效关系,为明确重楼抗肝癌作用的物质基础提供实验依据。方法:采用HPLC建立3种重楼提取物的指纹图谱,流动相乙腈(A)-水(B)梯度洗脱(0～10 min,20%A; 10～20 min,20%～25%A; 20～30 min,25%～30%A; 30～40 min,30%～35%A; 40～50 min,35%～40%A; 50～60 min,40%A; 60～75 min,40%～45%A; 75～80 min,45%～60%A),流速0. 9 m L·min~(-1),检测波长203 nm;利用噻唑蓝(MTT)比色法测定3种重楼提取物对肝癌HepG2细胞的增殖抑制作用,计算半数抑制浓度(IC_(50));运用聚类分析(HCA)和灰色关联度分析(GRA)研究3种重楼指纹图谱和抗肝癌作用的关系,找出对抗肝癌作用贡献较大的成分。结果:在3种重楼的HPLC指纹图谱中,确定其中11个色谱峰为共有峰。作用时间72 h时长柱重楼、滇重楼、南重楼的IC_(50)分别为148. 33,178. 87,208. 09 mg·L~(-1),其中长柱重楼的抗肝癌活性最强。灰色关联度结果显示,滇重楼共有峰中关联度较高的为1～10号峰,长柱重楼共有峰关联度较高的为1～7号峰,南重楼共有峰中关联度较高的为1～4,6～10,N1号峰,与IC_(50)关联度均0. 7。各重楼变量的聚类分析结果显示,可与IC_(50)聚为一类的色谱峰的关联度均 0. 7。结论:建立了3种重楼的HPLC指纹图谱,重复性良好。3种重楼中的1～4,6和7号色谱峰对抗肝癌药效贡献最大。     

石斛合剂对高脂高糖糖尿病大鼠心肌细胞Ca^2+代谢的影响

目的以糖尿病心肌病大鼠为研究对象,探讨石斛合剂对糖尿病心肌病心肌细胞Ca^2+代谢的影响。方法 Wistar大鼠24只,取5只作为正常组,余19只采用高脂高糖饮食联合链脲佐菌素腹腔注射进行糖尿病心肌病造模。成模后,随机分为模型组、二甲双胍组、石斛合剂组。二甲双胍组、石斛合剂组分别予二甲双胍、石斛合剂灌胃,正常组、模型组予生理盐水灌胃。4周后,测空腹血糖,取左心室心肌组织进行组织病理学观察和心肌细胞内游离钙(MyoCa^2+)浓度测定,Western blot法检测肌浆网Ca^2+-ATP酶(SERCA2a)、L型钙通道α1C亚单位蛋白(CACNA1C)蛋白表达,RT-PCR法测定SERCA2a mRNA表达。结果石斛合剂组心肌纤维较模型组、二甲双胍组排列整齐,断裂较少。与正常组比较,模型组血糖、心肌细胞MyoCa^2+含量和CACNA1C蛋白表达明显升高(P<0.01,P<0.05),SERCA2a mRNA和蛋白表达明显降低(P<0.01)。与模型组比较,石斛合剂组血糖、心肌细胞MyoCa^2+含量和CACNA1C蛋白表达明显降低(P<0.01,P<0.05),SERCA2a mRNA和蛋白表达明显升高(P<0.01,P<0.05);二甲双胍组血糖明显降低(P<0.01)。与二甲双胍组比较,石斛合剂组心肌细胞MyoCa^2+含量明显降低(P<0.01,P<0.05),血糖、SERCA2a mRNA和蛋白表达明显升高(P<0.05)。结论石斛合剂通过提高SERCA2a mRNA和蛋白表达,加快摄取Ca^2+的速率,降低细胞质Ca^2+负荷,缓解钙超载,最终达到维持糖尿病心肌病钙稳态的作用,有效维持心肌细胞的正常收缩舒张功能;其降糖作用不是预防糖尿病心肌病的主要机理,而在于抑制CACNA1C蛋白表达,抑制钙诱导钙释放过程。     

Hailey–Hailey disease improved by fractional CO2 laser

Hailey–Hailey disease (HHD), also known as benign familial pemphigus, is an autosomal dominant skin condition that affects the adhesion of epidermal keratinocytes. Although the initial manifestation of flaccid vesicles on erythematous or normal skin in flexure sites frequently goes unnoticed, large, macerated, exudative plaques of superficial erosions with crusting are observed at the time of diagnosis. There is no specific treatment for HHD, and most cases are symptomatically supported. However, infrared laser ablation has been somewhat helpful. We present a case successfully treated with fractional CO₂ laser showing a long-term favourable outcome and no adverse effects. Thus, this modality could be an alternative to full ablation for this condition.     

Reading the unique DNA methylation landscape of the brain: Non-CpG methylation,hydroxymethylation, and MeCP2

DNA methylation at CpG dinucleotides is an important epigenetic regulator common to virtually all mammalian cell types, but recent evidence indicates that during early postnatal development neuronal genomes also accumulate uniquely high levels of two alternative forms of methylation, non-CpG methylation and hydroxymethylation. Here we discuss the distinct landscape of DNA methylation in neurons, how it is established, and how it might affect the binding and function of protein readers of DNA methylation. We review studies of one critical reader of DNA methylation in the brain, the Rett syndrome protein methyl CpG-binding protein 2 (MeCP2), and discuss how differential binding affinity of MeCP2 for non-CpG and hydroxymethylation may affect the function of this methyl-binding protein in the nervous system.     

TGFβ promotes YAP‐dependent AXL induction in mesenchymal‐type lung cancer cells

The acquisition of chemoresistance remains a major cause of cancer mortality due to the limited accessibility of targeted or immune therapies. However, given that severe alterations of molecular features during epithelial‐to‐mesenchymal transition (EMT) lead to acquired chemoresistance, emerging studies have focused on identifying targetable drivers associated with acquired chemoresistance. Particularly, AXL, a key receptor tyrosine kinase that confers resistance against targets and chemotherapeutics, is highly expressed in mesenchymal cancer cells. However, the underlying mechanism of AXL induction in mesenchymal cancer cells is poorly understood. Our study revealed that the YAP signature, which was highly enriched in mesenchymal‐type lung cancer, was closely correlated to AXL expression in 181 lung cancer cell lines. Moreover, using isogenic lung cancer cell pairs, we also found that doxorubicin treatment induced YAP nuclear translocation in mesenchymal‐type lung cancer cells to induce AXL expression. Additionally, the concurrent activation of TGFβ signaling coordinated YAP‐dependent AXL expression through SMAD4. These data suggest that crosstalk between YAP and the TGFβ/SMAD axis upon treatment with chemotherapeutics might be a promising target to improve chemosensitivity in mesenchymal‐type lung cancer.

Abbreviations

AUC

area under the curve

AXL

AXL receptor tyrosine kinase

BCL2

B‐cell lymphoma 2

CTD2

cancer target discovery and development

CTGF

connective tissue growth factor

DEG

differentially expressed genes

DOXO

doxorubicin

EMT

epithelial–mesenchymal transition

Eto

etoposide

FDA

Food and Drug Administration

ITGB3

integrin beta‐3

MAPK

mitogen‐activated protein kinase

MMP2

matrix metalloproteinase‐2

MMP9

matrix metalloproteinase‐9

mRNA

messenger RNA

NF‐κB

nuclear factor kappa‐light‐chain‐enhancer of activated B cells

SBE

SMAD binding element

SERPINE1

serpin family E member 1

siRNA

small interfering RNA

ssGSEA

single‐sample gene set enrichment analysis

TCGA

The Cancer Genome Atlas

TGFβ

transforming growth factor beta

YAP

Yes‐associated protein

YAP8SA

mutants of inhibitory phosphorylation site at eight serine to Alanine of YAP

ZEB1

zinc finger E‐box binding homeobox 1

ZEB2

zinc finger E‐box‐binding homeobox 2

     

CO2点阵激光早期控制唇裂二期整复术后瘢痕的疗效观察

目的观察比较CO₂点阵激光早期控制唇裂术后二期整复术术区瘢痕的临床疗效。方法治疗组为43例接受唇裂术后鼻唇畸形二期整复术的患者，早期采用CO₂点阵激光治疗，对照组为70例曾接受一期唇裂手术的患者，对两组6个月后的瘢痕恢复情况进行比较；分析术后距离激光开始治疗时间的长短，性别两因素对激光治疗瘢痕疗效的差异。结果1）治疗组的疗效优于对照组（P<0.000 1），治疗组中显效和有效所组成的总有效率达90.7%；2）男女疗效差异无统计学意义（P=0.487），手术后1年内的患者，手术后距离开始瘢痕治疗的时间<3个月与≥3个月之间，疗效无明显统计学差异（P=0.055）。结论CO₂点阵激光在唇裂二期整复术术后瘢痕的治疗中具有较为确切的疗效。且与患者的性别无明显相关性。手术后1年内的患者，术后距离开始瘢痕治疗的时间<3个月和≥3个月疗效无差异，因此在唇裂二期手术后的1年内早期对瘢痕进行干预可获得良好的效果。     

Treatment strategies for hypertension in patients with type 1 diabetes

ABSTRACT

Introduction

Type 1 diabetes mellitus (T1DM) is a chronic, autoimmune disease that is characterized by total absence of insulin production. Hypertension is a common comorbidity in T1DM with complex pathophysiology, while it is also a well-recognized risk factor for the development of cardiovascular disease (CVD), as well as other microvascular diabetic complications.