基于iTRAQ技术探讨人胃癌细胞乙酰肝素酶调控的信号通路北大核心

目的:探讨人胃癌细胞中乙酰肝素酶(HPSE)调控的差异蛋白和信号通路,为以HPSE为靶点防治胃癌提供依据。方法:利用siRNA干扰技术,在乙酰肝素酶(HPSE)基因高表达的SGC7901细胞中转入干扰HPSE的慢病毒载体(LV-HPSE-RNAi),通过嘌呤霉素筛选出稳定株,利用qPCR和Western blot分别检测HPSE mRNA和蛋白表达;利用细胞划痕实验和Transwell侵袭实验测定细胞的迁移和侵袭能力;利用同位素标记的相对和绝对定量(iTRAQ)联合二维液相色谱串联质谱(2DLC-MS/MS)技术筛查差异蛋白,并进行生物信息学分析,对差异蛋白PKCa应用Western blot进一步验证。结果:人胃癌SGC7901细胞和沉默HPSE表达的ZSGC7901细胞对比检测出98个差异蛋白,并且富集在157条信号通路上。与肿瘤发生发展关系密切的有6条:细胞外基质和受体相互作用、局灶性黏附、PI3K-Akt信号通路、癌途径、癌中microRNAs、Wnt信号通路。且上调的FAK、ITGA、PKCa等蛋白和下调的PKA、CDK6等蛋白在通路中处于重要的位置。Western blot结果证明PKCa在沉默HPSE的ZSGC7901细胞中表现为上调,差异具有统计学意义(P<0.05),与蛋白质组学筛选结果一致。结论:HPSE在人胃癌细胞中调控的蛋白,参与细胞重要生物学过程、参与重要分子功能及重要信号途径,有望可以成为防治胃癌的新靶点。     

Involvement of Patients and Medical Professionals in the Assessment of Relative Effectiveness: A Need for Closer Cooperation

ObjectivesInvolvement of patients and medical professionals in assessment of relative effectiveness (relative effectiveness assessment) contributes to an efficient and effective health technology assessment (HTA) process and supports acceptance and implementation of the outcome. This study aimed to analyze stakeholder involvement in assessing relative effectiveness and how the parties involved value this collaboration.MethodsThis is a document analysis of all drug assessments completed in 2019 (20) by the public HTA agency of The Netherlands, enriched with semistructured interviews with employees of the HTA agency (18) and representatives of patient (5) and medical (11) associations involved in these assessments. Data were analyzed, coded, and categorized.ResultsIn almost half of the assessments, there was no coordination with the medical associations at the start of the relative effectiveness assessment and no patient associations involved in this phase. During the assessment procedure, patient and medical associations were always asked to comment on the draft report. Nevertheless, the strict 5-day deadline that the HTA agency uses as a response period often hampered a proper response and involvement. According to interviewees of the HTA agency, this leads to a great diversity in the substantive quality of their input. Patient and medical associations indicated that the HTA agency relies too much on “paper knowledge,” which leads to a (perceived) lack of alignment with clinical practice.ConclusionsThe limited involvement results in a lack of coordination and mutual trust. Optimizing involvement of patients and medical professionals in HTA practice requires effort from all parties involved. Procedural adjustments and better coordination, especially at the start of the assessment, would probably improve cooperation.     

青年人群近距离工作后眼部参数的变化及恢复时间

目的：观察青年人群近距离用眼后眼部生理及功能性参数的变化及恢复时间。

方法：前瞻性研究。随机选取2019-12/2020-06在我院进行医学验光的患者69例138眼，根据主觉验光结果分为正视组(+0.75D≤等效球镜度≤-0.50D，18例36眼)、低度近视组(-0.75D≤等效球镜度≤-3.00D，25例50眼)和中度近视组(-3.25D≤等效球镜度≤-6.00D，26例52眼)。所有受试者近距离阅读20min后远眺放松20min，分别于近距离用眼前、近距离用眼20min后、远眺5、10、15、20min时测量受试者眼部生理性参数\〖前房深度(ACD)、眼轴长度(AL)\〗和功能性参数\〖正相对调节(PRA)、调节反应(BCC)\〗，分析各参数的达极时间和恢复时间。

结果：近距离用眼后眼轴变长，前房变浅，PRA绝对值变大，BCC无明显变化，75%(52/69)的受试者AL在近距离用眼20min后达极，87%(60/69)的受试者ACD在远眺5min时达极，96%(66/69)的受试者PRA在近距离用眼20min后达极，且以上参数均在远眺10min后逐渐恢复至初始状态。

结论：近距离用眼后眼部参数发生改变，眼轴变长，前房变浅，PRA绝对值增大，但均在远眺放松过程中逐渐回退，且均需要10min以上才能恢复至初始状态。     

Changes in the National Endovascular Management of Femoropopliteal Arterial Disease: An Analysis of the 2011–2019 Medicare Data

PurposeTo describe national trends in the utilization of endovascular approaches (including balloon angioplasty, atherectomy, and stent placement) for the management of femoropopliteal peripheral arterial disease (PAD).Materials and MethodsThe Medicare Physician/Supplier Procedure Summary dataset containing 100% of Part B claims was interrogated for years 2011–2019. The Current Procedural Terminology codes specific for femoropopliteal angioplasty, stent placement, and atherectomy were used to create summary statistics for utilization by year, place of service (hospital inpatient, hospital outpatient, and office-based laboratory), and provider specialty (cardiology, radiology, and surgery).ResultsThe use of atherectomy increased from 34,732 (33%) procedures in 2011 to 75,435 (53%) procedures in 2019, and atherectomy became the dominant treatment strategy for femoropopliteal PAD. The relative utilization of stent placement (36,793 [35%] to 28,899 [20%]) and angioplasty only (34,398 [32%] to 38,228 [27%]) decreased concomitantly from 2011 to 2019. By 2019, the use of atherectomy was twofold higher in office-based laboratories than in the outpatient hospital setting (44,767 and 20,901, respectively). Treatment strategy varied by provider specialty in 2011 when cardiologists used atherectomy most frequently (17,925 [43%]), whereas radiologists used angioplasty alone (5,928 [6%]) and surgeons stented (18,009 [37%]) most frequently. By 2019, all specialties utilized atherectomy most frequently (29,564 [59%] for cardiology, 10,912 [58%] radiology, and 33,649 [47%] surgery).ConclusionsThe national approach to endovascular management of femoropopliteal PAD has changed since 2011 toward an implant-free strategy, including a multifold increase in the use of atherectomy. Discordant rates of atherectomy use between the ambulatory hospital and office-based settings highlight the need for comparative effectiveness studies to guide management.     

不同介入方案治疗急性下肢静脉血栓的临床效果与安全性比较

目的 探讨不同介入方案治疗急性下肢静脉血栓(DVT)的临床效果与安全性。方法 选取我院2015年1月～2019年12月介入科收治的急性DVT患者54例作为研究对象,按照治疗方式的不同分为研究组27例和对照组27例。研究组采用血管腔内综合治疗,对照组采用导管介导溶栓治疗,比较两组患者疗效评价、治疗前后膝上、下15 cm与患肢周径差、治疗前后皮肤肿胀张力、静脉通畅率、住院时间和并发症发生情况。结果 经治疗后研究组患者膝上、下15 cm与患肢周径差均短于对照组(P0.05);经治疗后研究组患者皮肤肿胀张力恢复程度显著优于对照组(P0.05);经治疗后研究组患者静脉通畅率显著高于对照组(P0.05);研究组治疗有效率显著高于对照组(P0.05);研究组患者住院时间明显少于对照组,且其并发症发生率显著低于对照组(P0.05)。结论 血管腔内综合介入治疗能够有效改善患者下肢症状,提高DVT恢复情况,降低并发症的发生,从而有效提高患者生活质量,为临床治疗DVT提供重要参考。     

苓桂术甘汤中多糖结构组成及其抗氧化活性考察

目的:研究苓桂术甘汤中多糖的结构,包括单糖组成以及官能团检测,并对其抗氧化能力进行评估,为体外生物测定法运用于苓桂术甘汤的质量评价提供基础。方法:利用高效凝胶色谱对全方多糖分子量进行研究;进一步采用气相色谱-质谱(GC-MS)柱前衍生化法及红外光谱扫描分析全方多糖结构组成;采用1,1-二苯基-2-三硝基苯肼(DPPH)及羟基自由基测定全方粗多糖及精多糖的抗氧化能力。结果:全方多糖由单一峰组成,且相对分子质量为3 689 Da,主要由阿拉伯糖、甘露糖、葡萄糖、半乳糖、果糖组成,摩尔比为6. 85∶1. 00∶109. 21∶1. 04∶21. 82,其中葡萄糖和果糖为主要组成成分;红外结果显示聚糖结构中存在吡喃糖及糖醛酸,并且糖苷键存在2种立体异构(α-糖苷键及β-糖苷键);抗氧化研究发现全方多糖有一定清除DPPH自由基及羟基自由基的能力,粗多糖的活性优于精多糖。进一步采用LC-Q-TOF-MS对粗多糖中的其他成分进行定性分析,提示这与甘草中五环三萜类成分的吸附有关。结论:苓桂术甘汤中多糖及五环三萜类物质均是苓桂术甘汤抗氧化作用的物质基础,利用体外生物测定法测定抗氧化活性可作为全面控制苓桂术甘汤质量的评价指标。     

Characteristics and risk factors of bortezomib induced peripheral neuropathy: A systematic review of phase III trials

Bortezomib-induced peripheral neuropathy (BIPN) is a common toxicity associated with the treatment of multiple myeloma (MM), typically requiring dose reduction, delay, or cessation of treatment protocol. This systematic review aimed to investigate risk factors, trends, and variability associated with the development of BIPN. Searches were undertaken using Medline, PubMed, Cochrane Central Register of Controlled Trials, Embase, Scopus, and Web of Science. Additional studies were identified by investigating authors' bibliographic references cited by original and review articles. Articles that reported on neuropathy in phase III randomised control trials involving bortezomib in any treatment arm for the treatment of MM were included in this review. A total of 43 full text articles met criteria, which examined 23 phase III trials (N = 8218). Overall incidence of neuropathy ranged from 8.4% to 80.5% (median = 37.8%) and severe neuropathy (grade 3-4) ranged from 1% to 33.2% (median = 8%). Similar reports of neuropathy of any grade and severe neuropathy were observed between the newly diagnosed and relapsed cohort. Bortezomib regimens with reduced dose intensity were associated with reduced neuropathy incidence. Increased cumulative dosing levels, intravenous compared with subcutaneous administration and combination therapy with thalidomide were associated with higher rates of BIPN. This analysis revealed that BIPN is a significant toxicity. More sensitive measures are required to capture the incidence and severity of BIPN. Better understanding of risk factors and reversibility profiles will minimise the number of cancer survivors living with residual treatment side effects.