踇甲皮瓣联合腓动脉穿支皮瓣游离移植再造拇指并修复足部供区 15 例

目的总结应用踇甲皮瓣再造拇指及腓动脉穿支皮瓣游离移植修复足部供区的手术方法及临床效果。方法2016 年 6 月—2018 年 5 月，应用踇甲皮瓣联合腓动脉穿支皮瓣游离移植再造拇指并修复足部供区 15 例。男 10 例，女 5 例；年龄 21～48 岁，平均 34.6 岁。致伤原因：重物压砸伤 7 例，机器绞伤 5 例，电锯切割伤 3 例。Ⅰ度缺损 9 例，Ⅱ度缺损 6 例。入院至皮瓣手术时间 4～7 d，平均 5.2 d。结果术后踇甲皮瓣及腓动脉穿支皮瓣全部成活，切口均Ⅰ期愈合。患者均获随访，随访时间 8～24 个月，平均 16.4 个月。末次随访时，再造拇指指甲生长平整，有光泽，指腹饱满；足部皮瓣外形良好，颜色及质地接近受区。根据中华医学会手外科学会拇手指再造功能评定标准，获优 9 例、良 6 例；根据 Maryland 足功能评分标准，获优 10 例、良 5 例。患者行走步态正常，无跛行及疼痛不适。结论踇甲皮瓣修复拇指Ⅰ、Ⅱ度缺损，再造拇指可获得良好外观及功能；腓动脉穿支皮瓣具有血供可靠、血管恒定、易切取等优点，可有效修复足部供区。     

Matrix metalloproteinase 9 (MMP9) level and MMP9 -1562C>T in patients with obstructive sleep apnea: a systematic review and meta-analysis of case-control studies

BackgroundThe peripheral level of matrix metalloproteinase (MMP)-9 and polymorphism of MMP9 -1562C>T in patients with obstructive sleep apnea (OSA) remains controversial. Therefore, the aims of this systemic review and meta-analysis are to assess the MMP9 level in OSA patients and identify the relationship between MMP9 -1562C>T and OSA susceptibility.MethodsThis systematic review was performed following the PRISMA guideline. We searched for studies in major databases, identifying those indexed from inception to July 3, 2019 which related to MMP9 level, MMP9 -1562C>T and OSA. The pooled standardized mean differences (SMDs) and 95% confidence interval (CI) of MMP9 levels were calculated. In addition, the relationship between MMP9 -1562C>T and OSA susceptibility was assessed by three genetic models. The heterogeneity analysis and calculation of the pooled odds ratio (OR) were also performed, followed by quality assessment using the Newcastle-Ottawa Scale (NOS).ResultsIn sum, our review included 15 eligible studies regarding MMP9 level and three regarding MMP9 -1562C>T. The pooled results showed that peripheral level of MMP9 was increased in OSA patients (SMD = 1.37; 95% CI = 1.15–1.59). Furthermore, significant difference of MMP9 level can be found between severe and mild-to-moderate OSA patients (SMD = 28.17; 95% CI = 4.23–52.11) or between moderate-severe and mild OSA (SMD = 36.62; 95% CI = 12.19–61.04). However, no relationship was observed between MMP9 -1562C>T and OSA susceptibility in three genetic models (Homozygote model, OR = 1.37; 95% CI = 0.87–2.18); (Recessive model, OR = 1.42; 95% CI = 0.83–2.42); (Allele model, OR = 1.07; 95% CI = 0.96–1.18).ConclusionsThis systemic review and meta-analysis indicated that the level of MMP9 was increased in patients with OSA and this increase is relevant to OSA severity. Moreover, the relationship between MMP9 -1562 C>T and OSA susceptibility has currently not been proven by current merging values. Further analyses with larger sample size are required to verify these associations.     

免疫检查点抑制剂治疗少见突变非小细胞肺癌疗效的研究进展

驱动基因的发现及针对驱动基因的靶向治疗已显著提高了肺癌患者的生存质量和时间，但目前对于BRAF、HER2、MET、RET等少见驱动基因改变肺癌患者的靶向药物的选择仍然较少。近年来免疫检查点抑制剂在肺癌治疗中取得了一定的疗效，但因为少见驱动基因突变的肺癌患者本身样本量少，开展大规模临床随机对照试验尚存在一定的困难，目前此类患者接受免疫检查点抑制剂治疗的疗效情况仍不明确。本文将对目前已掌握的免疫检查点抑制剂治疗BRAF、HER2、MET、RET等少见驱动基因改变肺癌患者的临床研究结果进行综述，以期在一定程度上为临床工作提供一些依据和参考。     

液相色谱-电喷雾串联质谱分析人全血中环孢素的基质效应评估及其机理探究

目的： 评估液相色谱-电喷雾串联质谱（LC-ESI-MS/MS）分析人全血中环孢素的基质效应，并探究其发生机理。方法： 全血裂解物的蛋白沉淀上清液用作全血基质。分别用乙腈水溶液和全血基质配制等浓度环孢素A（CyA）、环孢素C（CyC）的质控样品。分别在添加H⁺、NH₄⁺和Na⁺的流动相中，用LC-ESI-MS/MS的MRM模式检测质控样品中CyA，CyC的[M+H]⁺、[M+NH₄]⁺和[M+Na]⁺（M=CyA，CyC）峰面积，以其计算基质效应因子；用MS Scan模式检查质控样品中CyA、CyC色谱流出峰的质谱离子组成情况，用于判断基质效应原因。结果： 在添加H⁺、NH₄⁺和Na⁺的流动相中，全血基质中CyA、CyC基质效应因子分别为-76.6%~-54.0%、-86.0%~-55.3%和-42.8%~-34.1%。在加H⁺、加NH₄⁺流动相中，标准液加全血基质的CyA、CyC色谱峰的质谱中出现丰度很高的[M+Na]⁺和[M+K]⁺，在加Na⁺流动相中它们出现丰度很高的[M+K]⁺，而对应的定量离子[M+H]⁺、[M+NH₄]⁺或[M+Na]⁺的丰度显著降低。结论： 全血基质对环孢素的LC-ESI-MS/MS分析产生明显的基质效应，其原因与基质中Na⁺、K⁺同添加在流动相中用于辅助电离的H⁺、NH₄⁺或Na⁺竞争与环孢素加合，导致定量目标加合离子丰度显著降低有关。     

Ets-1、MMP-1及TIMP-1在膀胱移行细胞癌中的表达

目的研究Ets-1、基质金属蛋白酶1(MMP-1)及基质金属蛋白酶1抑制物(TIMP-1)在膀胱移行细胞癌(BTCC)中的表达及意义。方法用免疫组化方法检测40例BTCC组织和12例正常膀胱黏膜组织中Ets-1、MMP-1及TIMP-1的表达;分析Ets-1与BTCC临床病理特征间的关系;研究BTCC中MMP-1、TIMP-1表达与Ets-1表达的相关性。结果①Ets-1在BTCC中高度表达,阳性率为82.5%(P<0.01),且随BTCC临床分期和病理分级的升高而增加,肿瘤复发组高于无复发组,肿瘤转移组高于无转移组(P<0.05)。②MMP-1阳性表达率膀胱癌组(85.0%)明显高于对照组(58.3%)(p<0.05);TIMP-1阳性表达率对照组(83.3%)明显高于膀胱癌组(47.5%)(P<0.05)。③MMP-1与Ets-1表达呈正相关(Rs为0.824,P<0.01),而TIMP-1与Ets-1表达呈负相关(Rs为-0.821,P<0.01)。结论①Ets-1在BTCC中高度表达,并随BTCC分期分级升高而增加;Ets-1与BTCC转移及复发密切相关。②BTCC中Ets-1上调MMP-1表达,而下调TIMP-1表达,从而参与BTCC侵袭与转移。