Synergism through combination of chemotherapy and oxidative stress-induced autophagy in A549 lung cancer cells using redox-responsive nanohybrids: A new strategy for cancer therapy

A combination of various therapeutic approaches has emerged as a promising strategy for cancer treatment. A safe and competent nano-delivery system is thus in urgent demand to facilitate the simultaneous transport of various therapeutic agents to cancer cells and a tumor region to achieve synergistic effect. Gold nanoparticles (GNPs) and mesoporous silica nanoparticle (MSNs) were fabricated herein as potential candidates for drug delivery. Serving as gatekeepers, GNPs (5 nm in diameter) were attached onto the amino-functionalized MSNs (denoted as NMSNs) via a relatively weak gold–nitrogen bonding. The resulting nanohybrids (denoted as GCMSNs) were uptaken by cells, and the detachment of GNPs and subsequent intracellular drug release from NMSNs were achieved by competitive binding of intracellular glutathione to GNPs. In addition to the function of gatekeeping, GNPs also play another role as the oxidative stress elicitor. Our in vitro studies revealed that GCMSNs induced higher oxidative stress in lung cancer cells (A549) than in normal cells (3T3-L1). This growth inhibitory effect found in the cancer cells was likely induced by mitochondria dysfunction originated from the GCMSN-induced, oxidative stress-triggered mitochondria-mediated autophagy. The redox-responsive nanohybrids were further loaded with camptothecin and the intensified synergistic therapeutic effects were observed associated with combined chemotherapy and oxidative stress strategy. The results clearly demonstrate that such unique nanohybrids hold great promise for selective and effective cancer treatments.     

Marr and Reductionism

David Marr's three-level method for completely understanding a cognitive system and the importance he attaches to the computational level are so familiar as to scarcely need repeating. Fewer seem to recognize that Marr defends his famous method by criticizing the “reductionistic approach.” This sets up a more interesting relationship between Marr and reductionism than is usually acknowledged. I argue that Marr was correct in his criticism of the reductionists of his time—they were only describing (cellular activity), not explaining (cognitive functions). But a careful metascientific account of reductionistic neuroscience over the past two decades reveals that Marr's criticisms no longer have force. Contemporary neuroscience now explains cognition directly, although in a fashion—causal-mechanistically—quite different than Marr recommended. So while Marr was correct to reject the reductionism of his day and offer an alternative method for genuinely explaining cognition, contemporary cognitive scientists now owe us a new defense of Marr's famous method and the advantages of its explanations over the type now pursued successfully in current reductionist neuroscience. There are familiar reasons for thinking that this debt will not be paid easily.     

The role of National Immunization Technical Advisory Groups (NITAG) in strengthening health system governance: Lessons from three middle-income countries—Argentina,Jordan, and South Africa (2017–2018)

IntroductionToward the Global Vaccine Action Plan 2020 goal, almost 90% of countries have established a National Immunization Technical Advisory Group (NITAG). However, little is known about NITAG's contributions to governance.MethodsIn 2017–2018, a two-step, qualitative retrospective study was conducted. Jordan (JO), Argentina (AR), and South Africa (SA) were selected owing to government-financed NITAGs from middle-income countries (MICs), geographic diversity, and a vaccine introduction with NITAG support. Country case studies were developed, collecting data through desk review and face-to-face key informant interviews (KIIs) from Ministry of Health (MoH) and NITAG. Case studies were analyzed together, to assess governance applying the European Observatory on Health Systems and Policies framework focusing on transparency, accountability, participation, integrity, and policy capacity (TAPIC).ResultsDocument review and 53 KII (22 AR, 20 SA, 11 JO) showed NITAGs played a pivotal role as advisors promoting a culture of evidence-informed policies. NITAGs strengthened governance, although practices varied among countries. Meetings were conducted behind-closed-doors, participation restricted to members, only in one country agendas, and recommendations were public (AR). To increase participation, policy capacity, and transparency, countries considered adding experts in communications, advocacy, and economics. AR and SA contemplated including community members. NITAGs functioned autonomously from the government, with no established internal or external monitoring or supervision. NITAG meeting minutes allowed the review of integrity, adherence to terms of reference, standard operating procedures, and conflict of interest (CoI). For the most part, NITAGs abided by their mandates. Significant issues were related to the level of MoH support and oversight of CoI declaration and documentation.ConclusionsSystematically implementing governance approaches could improve processes, better tailor policies, and implementation. The long-term survival and resilience of NITAGs in these countries showed they play a significant role in strengthening governance. Lessons learned could be useful to those promoting country-driven evidence-informed decision-making.     

模拟诊疗在留学生心血管内科实习带教中的应用研究

目的　探讨模拟诊疗在留学生心血管内科实习带教中的应用效果。方法　将35名留学生随机编号，分成试验组和对照组。试验组18名学生分成3组（每组6名）进行模拟诊疗教学，对照组17名学生进行常规实习。通过填写评价单和相关的临床能力测试对两组教学效果进行评价。选用SPSS 19.0软件进行t检验。结果　参与模拟诊疗教学的留学生均希望在各科实习中多采用此方法。在临床能力测试方面，试验组学生在病史采集[（22.16±2.17）vs.（20.33±2.03）]、体格检查[（23.05±1.79）vs.（19.78±2.05）]及回答问题[（23.50±1.47）vs.（19.56±1.92）]方面均优于对照组，差异有统计学意义（P<0.05）。但是在病历书写方面，两组差异无统计学意义（P>0.05）。结论　利用高仿真的模拟诊疗教学手段，弥补了留学生在实习期间不能充分接触患者的缺陷，有助于提高其临床操作技能、增强医患沟通能力等医学职业素养。     

Relationship between EMG-detected and ultrasound-detected fasciculations in amyotrophic lateral sclerosis: A prospective cohort study

ObjectivesFasciculation potentials (FP) are an important consideration in the electrophysiological diagnosis of ALS. Muscle ultrasonography (MUS) has a higher sensitivity in detecting fasciculations than electromyography (EMG), while in some cases, it is unable to detect EMG-detected fasciculations. We aimed to investigate the differences of FP between the muscles with and without MUS-detected fasciculations (MUS-fas).MethodsThirty-one consecutive patients with sporadic ALS were prospectively recruited and in those, both needle EMG and MUS were performed. Analyses of the amplitude, duration, and number of phases of EMG-detected FPs were performed for seven muscles per patient, and results were compared between the muscles with and without MUS-fas in the total cohort.ResultsThe mean amplitude and phase number of FP were significantly lower in patients with EMG-detected FP alone (0.39 ± 0.25 mV and 3.21 ± 0.88, respectively) than in those with both FP and MUS-fas (1.22 ± 0.92 mV and 3.74 ± 1.39, respectively; p < 0.0001 and p = 0.017, Welch’s t-test).ConclusionSmall FP may be undetectable with MUS. MUS cannot replace EMG in the diagnostic approach for ALS.SignificanceClinicians should use a combination of EMG and MUS for the detection and quantitative analysis of fasciculation in ALS.     

新型冠状病毒肺炎疫情下喉镜检查的防护策略

目的探讨新型冠状病毒肺炎（COVID 19）疫情下耳鼻咽喉头颈外科喉镜室如何做好防护工作，在保证临床诊疗工作顺利完成的同时保护好医务人员及患者健康、避免院内交叉感染。方法本研究查阅相关资料并总结医院的疫情防控经验及应对策略，在患者合理分流、喉镜室工作环境的布置及工作人员的个人防护、喉镜检查前的准备工作、检查中的操作流程及注意事项及检查后的清洁消毒工作等方面做好疫情期间周详合理的工作安排。结果疫情期间，耳鼻咽喉头颈外科喉镜室每日临床工作顺利完成，所有医务人员及患者均未感染新型冠状病毒，也未出现其他院内交叉感染。结论耳鼻咽喉头颈外科喉镜室的防护策略合理有效，能够在完成临床诊疗工作的同时有效保护医患的健康。     

甘肃省和政县农村老年性白内障防盲项目的卫生经济学评价研究

目的 对2014-2016年在甘肃省和政县开展的白内障综合防盲干预项目进行卫生经济学评价。设计 横断面调查。 研究对象 甘肃省和政县2014-2016年老年性白内障手术前407例患者及术后半年109例患者。方法 对所有调查对象进行卫生经济学问卷调查。通过净效益法、成本效益分析法和成本效果分析法评价项目产生的经济效益和总成本。主要指标 直接成本、间接成本、直接经济效益、间接经济效益、总成本、总效益、净效益、成本效益比、成本效果比。结果 2014-2016年项目期间甘肃省和政县白内障所致总体疾病经济负担为2142.28万元。白内障手术产生的总效益为3398424.98元，总成本为2939125.20元，净效益为459299.78元，效益成本比为1.16:1。项目每投入1万元可降低50岁以上白内障患者导致的0.027%的致盲率和0.164%致残率；项目每降低1%的50岁以上白内障患者的盲率，需投入36.47万元；每降低1%50岁以上白内障患者的残率，需投入6.11万元。结论 在甘肃省和政县开展的老年性白内障防盲综合干预项目具有较好的产出回报比和较高的防盲技术效率。（眼科，2020，29： 298-303）