高渗盐水和甘露醇在动脉瘤性蛛网膜下腔出血患者降低颅内压中的应用

目的比较3%高渗盐水和20%甘露醇治疗重症动脉瘤性蛛网膜下腔出血所致颅内压增高的疗效.方法25例动脉瘤性蛛网膜下腔出血患者出现颅内压增高事件时, 随机交替接受等渗透剂量的160 mL 3%高渗盐水与150 mL 20%甘露醇进行降低颅内压治疗, 连续监测患者颅内压、平均动脉压、脑灌注压及中心静脉压.记录有效降低颅内压持续时间、颅内压最大降幅及其时间, 用药前及用药后1 h、3 h血钠水平及血浆渗透压.结果3%高渗盐水和20%甘露醇均可降低颅内压(均 P < 0.01), 两者的降低颅内压作用持续时间及颅内压降幅差异均无统计学意义(均 P >0.05).患者脑灌注压较用药前均上升(均 P < 0.01), 平均动脉压先上升后下降, 但差异无统计学意义( P >0.05).患者中心静脉压稍有波动, 但差异均无统计学意义(均 P >0.05).20%甘露醇治疗后患者血钠下降, 3%高渗盐水治疗后患者血钠值上升, 变化均有统计学意义(均 P < 0.05).20%甘露醇及3%高渗盐水治疗后患者血浆渗透压均先上升后下降, 变化均有统计学意义(均 P < 0.01). 结论3%高渗盐水可作为治疗动脉瘤性蛛网膜下腔出血所致颅内压增高患者的一线治疗药物.     

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

     

CD44基因多态性与宫颈癌及非小细胞肺癌的相关性

背景与目的：CD44分子是众多肿瘤细胞的标志分子，其表达水平与肿瘤细胞的恶性程度有关。该研究探讨CD44基因中的单核苷酸多态性（single nucleotide polymorphism，SNP）位点与云南汉族人群宫颈癌和非小细胞肺癌（nonsmall cell lung cancer，NSCLC）易感性的相关性。方法：选取了CD44基因中的两个SNP位点rs13347和rs8193，采用TagMan基因分型的方法，分析这两个多态性位点在497例宫颈癌患者和500例健康对照个体以及483例NSCLC患者和471例健康对照个体中的分布特征，并分析CD44基因中的多态性位点与云南汉族人群宫颈癌和NSCLC的相关性。结果：rs13347和rs8193位点等位基因和基因型在宫颈癌组和对照组中的分布频率的差异无统计学意义（P>0.05）。而在NSCLC组和对照组的比较中：rs13347和rs8193位点等位基因在NSCLC组和对照组中的分布频率的差异有统计学意义（P=0.020和P=0.004）；这两个位点基因型在NSCLC组和对照组中分布频率的差异有统计学意义（P=0.027和P=0.020）；其中rs13347位点等位基因C在NSCLC组中的分布频率显著高于对照组，可能是NSCLC发生的风险因素（OR=1.250，95% CI：1.035～1.509），rs8193位点等位基因C在对照组中的分布频率显著高于NSCLC组，可能是NSCLC发生的保护性因素（OR=0.768，95%CI：0.641～0.921）。单倍型分析结果显示，rs13347C-rs8193T和rs13347T-rs8193C在NSCLC组和对照组中的分布频率差异有统计学意义（P=0.003和0.022）；该结果说明单倍型rs13347C-rs8193T可能是云南汉族人群NSCLC发生的风险性因素（OR=1.316，95%CI：1.096～1.579）。结论：CD44基因中的两个SNP位点rs13347和rs8193可能与云南汉族人群宫颈癌发病风险无关，而可能与云南汉族人群NSCLC具有相关性。     

八段锦治疗神经根型颈椎病的系统评价与Meta分析

[目的] 系统评价八段锦治疗神经根型颈椎病的临床疗效。[方法] 计算机检索中国知网数据库（CNKI）、维普资讯中文科技期刊数据库（VIP）、万方数据库（Wan-fang）、中国生物医学文献数据库（SinoMed）、Web of science、Clinical Trials gov、Pubmed、EMBASE、CENTRAL、Cochrane Library，查找出八段锦治疗神经根型颈椎病的随机对照试验（RCT），检索时限均从建库至2019年7月1日。两名研究者按照纳入与排除标准独立进行文献筛选、资料提取和偏倚风险评估，应用RevMan 5.3软件对最后纳入的研究进行Meta分析。[结果] 最终纳入10个RCT，共843例患者。Meta分析结果显示：八段锦+常规治疗与常规治疗比较，其临床疗效的总有效率差异具有统计学意义[OR=4.19，95% CI（2.42，7.26），P<0.000 01]；八段锦+常规治疗与常规治疗+颈部“米”字操比较，其临床疗效的总有效率差异具有统计学意义[OR=3.41，95% CI（1.56，7.46），P=0.002]；八段锦+常规治疗与常规治疗比较，其疼痛视觉模拟评分法（VAS）评分差异具有统计学意义[MD=-1.90，95% CI（-1.97，-1.83），P<0.000 01]。[结论] 基于现有的研究，该系统评价显示，与常规治疗相比，八段锦+常规治疗在临床疗效总有效率、VAS评分方面有一定的治疗优势。与常规治疗+颈部“米”字操比较，八段锦+常规治疗在临床疗效的总有效率方面有一定的治疗优势。但由于纳入研究的质量不高，仍需要大样本、多中心、随机、双盲试验及试验参照CONSORT标准和STRICTA声明进行RCT研究。     

Biodegradable versus titanium osteosynthesis in maxillofacial traumatology: a systematic review with meta-analysis and trial sequential analysis

Titanium osteosynthesis is currently the fixation system of choice in maxillofacial traumatology. Biodegradable osteosynthesis systems have the ability to degrade in the human body. The aim of this study was to conduct a systematic review, with meta- and trial sequential analyses, to assess the efficacy and morbidity of biodegradable versus titanium osteosynthesis after maxillofacial trauma. MEDLINE, Embase, and CENTRAL were searched for randomized controlled trials and prospective and retrospective controlled studies. Five time periods were studied: perioperative, short-term (0–4 weeks), intermediate (6–12 weeks), long-term (>12 weeks), and overall follow-up. After screening 3542 records, 24 were included. All had a high risk of performance and detection bias due to the nature of the interventions. Meta-analysis showed no differences in efficacy or morbidity between biodegradable and titanium osteosynthesis. The risk of perioperative screw breakage was significantly higher (risk ratio 17.13, 95% confidence interval 2.19–34.18) and the symptomatic plate removal rate lower in the biodegradable group (risk ratio 0.11, 95% confidence interval 0.02–0.57), which was confirmed by the trial sequential analysis. The quality of evidence ranged from very low to moderate. Based on the narrative review and meta-analyses, current evidence shows that biodegradable osteosynthesis is a viable alternative to titanium osteosynthesis when applied in the treatment of maxillofacial trauma, with similar efficacy but significantly lower symptomatic plate removal rates. Perioperative screw breakage occurred significantly more often in the biodegradable group compared to the titanium group.     

颞下颌关节强直动物模型中最大张口度与强直严重程度关系研究

目的　研究主、被动最大张口度（AMMO、PMMO）与颞下颌关节强直严重程度的关系。方法　选取28只健康雄性绵羊随机分为实验组和对照组，每组各14只。实验组绵羊双侧颞下颌关节模拟髁突矢状骨折，其中左侧翼外肌被切断以阻断其功能；对照组绵羊未进行手术。于术前及术后12、24周对所有绵羊体重、AMMO、PMMO、颞下颌关节形态学特点进行测量评估。结果　实验组只有右侧保留翼外肌功能的颞下颌关节发生了骨强直。术后12、24周，实验组绵羊AMMO、PMMO、极限距离均显著低于对照组，差异均有统计学意义（均P < 0.05）。实验组绵羊AMMO和PMMO与骨融合区宽度、长度、面积及钙化程度均呈负相关（均P < 0.05），其中骨融合区面积为主要影响因素（术后12、24周相关系数r分别为-0.94、-0.95）。结论　颞下颌关节强直动物模型中阻断翼外肌功能可阻止骨强直的发生；对于早期髁突矢状骨折，可通过牙合垫或牙合板进行张口训练，进而阻断翼外肌功能。当颞下颌关节发生骨强直时，骨融合区面积越大，张口受限越明显。     

孟鲁司特治疗呼吸道合胞病毒毛细支气管炎症状及反复喘息疗效研究

背景　呼吸道合胞病毒（RSV）毛细支气管炎易出现反复喘息，且下呼吸道分泌物中半胱氨酸白三烯（CysLTs）水平升高。而孟鲁司特是一种白三烯受体拮抗剂，关于其治疗RSV毛细支气管炎症状的研究相对较少。目的　探讨孟鲁司特改善婴幼儿RSV毛细支气管炎后症状及减轻反复喘息发作的有效性和安全性。方法　2015年6月-2017年6月连续纳入在潍坊市妇幼保健院出院的RSV毛细支气管炎患儿，随机分为治疗组、对照组。Ⅰ期，治疗组：口服孟鲁司特颗粒（4 mg）12周，1次/d；对照组：口服安慰剂12周，1次/d。对两组无症状天数、个人日记评分进行评估。随访9个月（Ⅱ期），观察Ⅰ+Ⅱ期反复喘息人数和医疗资源应用情况等。依据意向性分析（ITT）原则，应用全分析集（FAS）分析数据。结果　共纳入研究对象186例，治疗组92例，对照组94例。治疗组完成Ⅰ期研究的患儿为89例，对照组为90例；治疗组完成Ⅰ+Ⅱ期的患儿为84例，对照组为86例。治疗组平均依从性为97.8%（7 560/7 728），对照组平均依从性为97.4%（7 690/7 896），两组患儿平均依从性比较，差异无统计学意义（χ2=3.16，P=0.07）。在Ⅰ期研究期间，两组无症状天数、日间无症状天数、夜间无症状天数、个人日记评分比较，差异均无统计学意义（P>0.05）。在整个研究过程中（Ⅰ+Ⅱ期），治疗组RSV毛细支气管炎喘息复发人数少于对照组（P<0.05），治疗组喘息患儿出现2次及以上喘息比例低于对照组（χ2=5.14，P=0.02）。Ⅰ+Ⅱ期研究期间治疗组医疗资源应用人数、β-受体激动剂应用人数、糖皮质激素应用人数、住院人数低于对照组（P<0.05）。在事后亚组分析中，治疗组有湿疹史与父母哮喘史的患儿中无症状天数〔（49.7±20.2）、（51.3±20.9）d〕多于对照组〔（36.3±20.4）、（37.8±19.3）d〕（t=2.19，P=0.03；t=2.24，P=0.03）。整个研究过程中没有患儿因不良反应退出研究，两组间胃肠道紊乱、皮疹、转氨酶升高发生率比较，差异均无统计学意义（χ2=0.23，P=0.63；χ2=0.03，P=0.86；χ2=0.15，P=0.69）。结论　口服孟鲁司特（4 mg）12周不能改善RSV毛细支气管炎患儿呼吸道症状，但能降低患儿反复喘息发作次数。口服孟鲁司特（4 mg）有一定效果且安全。     

Animal Models of Barrett's Esophagus and Esophageal Adenocarcinoma–Past,Present, and Future

Esophageal adenocarcinoma is the fastest rising cancer in the United States. It develops from long‐standing gastroesophageal reflux disease which affects >20% of the general population. It carries a very poor prognosis with 5‐year survival <20%. The disease is known to sequentially progress from reflux esophagitis to a metaplastic precursor, Barrett''s esophagus and then onto dysplasia and esophageal adenocarcinoma. However, only few patients with reflux develop Barrett''s esophagus and only a minority of these turn malignant. The reason for this heterogeneity in clinical progression is unknown. To improve patient management, molecular changes which facilitate disease progression must be identified. Animal models can provide a comprehensive functional and anatomic platform for such a study. Rats and mice have been the most widely studied but disease homology with humans has been questioned. No animal model naturally simulates the inflammation to adenocarcinoma progression as in humans, with all models requiring surgical bypass or destruction of existing antireflux mechanisms. Valuable properties of individual models could be utilized to holistically evaluate disease progression. In this review paper, we critically examined the current animal models of Barrett''s esophagus, their differences and homologies with human disease and how they have shaped our current understanding of Barrett''s carcinogenesis.