Decellularized Pig Kidney with a Micro-Nano Secondary Structure Contributes to Tumor Progression in 3D Tumor Model

In spite of many anti-cancer drugs utilized in clinical treatment, cancer is still one of the diseases with the highest morbidity and mortality worldwide, owing to the complexity and heterogeneity of the tumor microenvironment. Compared with conventional 2D tumor models, 3D scaffolds could provide structures and a microenvironment which stimulate native tumor tissues more accurately. The extracellular matrix (ECM) is the main component of the cell in the microenvironment that is mainly composed of three-dimensional nanofibers, which can form nanoscale fiber networks, while the decellularized extracellular matrix (dECM) has been widely applied to engineered scaffolds. In this study, pig kidney was used as the source material to prepare dECM scaffolds. A chemical crosslinking method was used to improve the mechanical properties and other physical characteristics of the decellularized pig kidney-derived scaffold. Furthermore, a human breast cancer cell line (MCF-7) was used to further investigate the biocompatibility of the scaffold to fabricate a tumor model. The results showed that the existence of nanostructures in the scaffold plays an important role in cell adhesion, proliferation, and differentiation. Therefore, the pig kidney-derived matrix scaffold prepared by decellularization could provide more cell attachment sites, which is conducive to cell adhesion and proliferation, physiological activities, and tumor model construction.     

伏立康唑血药浓度监测及其在血液系统肿瘤患者用药指导中的应用

目的:建立一种快速、灵敏、准确、稳定的测定人血清中伏立康唑药物浓度的方法,用于伏立康唑的治疗药物监测.方法:采用RP-HPLC法,色谱柱为Inertsil ODS-3,流动相为乙腈:冰醋酸-三乙胺缓冲液(pH=6,45:55,v/v),流速为1 mL·min-1,检测波长255 nm.结果:伏立康唑在0.097～23....     

Systemic Therapy and Its Surgical Implications in Patients with Resectable Liver Colorectal Cancer Metastases. A Report from the Western Canadian Gastrointestinal Cancer Consensus Conference

The Western Canadian Gastrointestinal Cancer Consensus Conference (WCGCCC) convened virtually on 4 November 2021. The WCGCCC is an interactive multi-disciplinary conference attended by health care professionals, including surgical, medical, and radiation oncologists; pathologists; radiologists; and allied health care professionals from across four Western Canadian provinces, British Columbia, Alberta, Saskatchewan, and Manitoba, who are involved in the care of patients with gastrointestinal cancer. They participated in presentation and discussion sessions for the purpose of developing recommendations on the role of systemic therapy and its optimal sequence in patients with resectable metastatic colorectal cancer.     

复方小柴胡汤对荷瘤小鼠NK细胞功能的影响

目的 探讨复方小柴胡汤(XCHT)对EAC荷瘤小鼠的免疫功能的影响.方法 用3种不同浓度的复方小柴胡汤对EAC荷瘤小鼠灌胃10 d,观察其肿瘤生长情况以及用乳酸脱氢酶释放法检测NK细胞的活性.结果 高、中和低浓度组NK细胞活性分别为(44.21±3.10)%,(51.09±4.94)%和(37.30±2.02)%,与空白对照组(31.26±2.79)%比较,NK细胞活性升高(P＜0.05),而阴性对照组(26.90±1.84)%NK细胞活性显著降低(P＜0.05);高、中和低浓度组的肿瘤质量为(300.6±48.9)mg,(226.5±36.4)mg和(445.9±60.2)mg,与阴性对照组(661.5±102.8)mg比较,均能抑制肿瘤的生长(P＜0.05),其中以中浓度组效果最为明显.结论 经过复方小柴胡汤灌胃的EAC荷瘤小鼠NK细胞活性均升高,3种不同浓度的复方小柴胡汤均使肿瘤生长减慢.     

Opposing Effects of Prior Infection versus Prior Vaccination on Vaccine Immunogenicity against Influenza A(H3N2) Viruses

Prior vaccination can alternately enhance or attenuate influenza vaccine immunogenicity and effectiveness. Analogously, we found that vaccine immunogenicity was enhanced by prior A(H3N2) virus infection among participants of the Ha Nam Cohort, Viet Nam, but was attenuated by prior vaccination among Australian Health Care Workers (HCWs) vaccinated in the same year. Here, we combined these studies to directly compare antibody titers against 35 A(H3N2) viruses spanning 1968–2018. Participants received licensed inactivated vaccines containing A/HongKong/4801/2014 (H3N2). The analysis was limited to participants aged 18–65 Y, and compared those exposed to A(H3N2) viruses circulating since 2009 by infection (Ha Nam) or vaccination (HCWs) to a reference group who had no recent A(H3N2) infection or vaccination (Ha Nam). Antibody responses were compared by fitting titer/titer-rise landscapes across strains, and by estimating titer ratios to the reference group of 2009–2018 viruses. Pre-vaccination, titers were lowest against 2009–2014 viruses among the reference (no recent exposure) group. Post-vaccination, titers were, on average, two-fold higher among participants with prior infection and two-fold lower among participants with 3–5 prior vaccinations compared to the reference group. Titer rise was negligible among participants with 3–5 prior vaccinations, poor among participants with 1–2 prior vaccinations, and equivalent or better among those with prior infection compared to the reference group. The enhancing effect of prior infection versus the incrementally attenuating effect of prior vaccinations suggests that these exposures may alternately promote and constrain the generation of memory that can be recalled by a new vaccine strain.     

脑震宁颗粒对三重脑震荡模型大鼠额颞叶皮质区线粒体生物合成的影响

目的 基于线粒体能量代谢,从生物合成角度探究脑震宁颗粒对脑震荡后综合征模型大鼠的记忆功能和神经元的影响。方法 SPF级Wistar大鼠,采用自由落体撞击法构建三重脑震荡模型（MCC）,依据模型评价标准将造模成功大鼠分为模型组,吡拉西坦组（0.324 g·kg^-1）,脑震宁低、中、高剂量组（2.25、4.5、9 g·kg^-1）,另设正常组,按剂量进行灌胃治疗,正常组和模型组给予等体积生理盐水,每天1次,连续14 d。观察大鼠给药前后的一般状态;采用旷场实验和新物体识别实验检测大鼠的运动和记忆能力;采用苏木素-伊红（HE）染色观察大鼠皮层组织神经元的病理改变;采用蛋白免疫印迹法（Western blot）和实时荧光定量聚合酶链式反应（Real-time PCR）检测大鼠组织过氧化物酶体增殖物激活受体γ-共激活因子-1α（PGC-1α）、核呼吸因子1（NRF-1）、线粒体转录因子（TFAM）的蛋白和mRNA表达。结果 与正常组比较,模型组大鼠精神焦虑狂躁,被毛萎黄脏乱,摄食量减少;旷场实验中模型大鼠的运动总路程、中央格进入次数和直立次数显著降低（P<0.01）,静止时间显著升高（P<0.01）;新物体识别指数显著下降（P<0.01）;皮层组织神经元数量减少,分布稀疏,核仁畸形、破裂,形态不规则;皮层组织PGC-1α、NRF-1、TFAM的蛋白表达水平均显著降低（P<0.01）;皮层组织PGC-1α、NRF-1、TFAM的mRNA表达水平均显著降低（P<0.01）。与模型组比较,吡拉西坦组和脑震宁各剂量组大鼠精神状态和被毛颜色改善,食欲增加,活动逐渐正常;旷场实验中大鼠的运动总路程、中央格进入次数和直立次数明显增高（P<0.05,P<0.01）,静止时间明显降低（P<0.05,P<0.01）;新物体识别指数明显上升（P<0.05,P<0.01）;皮层组织神经元数量增多,排列较为紧密,核大而圆,部分细胞形态不规则,胞浆浑浊;吡拉西坦组和脑震宁中剂量组皮层组织PGC-1α、NRF-1和TFAM蛋白表达显著升高（P<0.01）,脑震宁低剂量组大鼠皮层组织NRF-1和TFAM蛋白表达显著升高（P<0.01）,脑震宁高剂量组大鼠皮层组织PGC-1α和TFAM蛋白表达显著升高（P<0.01）;吡拉西坦组和脑震宁各剂量组皮层组织PGC-1α、NRF-1、TFAM mRNA表达水平明显升高（P<0.05,P<0.01）。结论 脑震宁颗粒可以改善MCC大鼠的运动探索和记忆学习状况,修复神经元损伤,保护神经功能,其作用机制可能与促进大脑皮层神经元的线粒体生物合成有关。     

What are the visuo-motor tendencies of omnidirectional scene free-viewing in virtual reality?

Central and peripheral vision during visual tasks have been extensively studied on two-dimensional screens, highlighting their perceptual and functional disparities. This study has two objectives: replicating on-screen gaze-contingent experiments removing central or peripheral field of view in virtual reality, and identifying visuo-motor biases specific to the exploration of 360 scenes with a wide field of view. Our results are useful for vision modelling, with applications in gaze position prediction (e.g., content compression and streaming). We ask how previous on-screen findings translate to conditions where observers can use their head to explore stimuli. We implemented a gaze-contingent paradigm to simulate loss of vision in virtual reality, participants could freely view omnidirectional natural scenes. This protocol allows the simulation of vision loss with an extended field of view (>80°) and studying the head''s contributions to visual attention. The time-course of visuo-motor variables in our pure free-viewing task reveals long fixations and short saccades during first seconds of exploration, contrary to literature in visual tasks guided by instructions. We show that the effect of vision loss is reflected primarily on eye movements, in a manner consistent with two-dimensional screens literature. We hypothesize that head movements mainly serve to explore the scenes during free-viewing, the presence of masks did not significantly impact head scanning behaviours. We present new fixational and saccadic visuo-motor tendencies in a 360° context that we hope will help in the creation of gaze prediction models dedicated to virtual reality.     

胰高血糖素样肽1受体激动剂类降糖药致2型糖尿病患者头疼和眩晕的网状Meta分析

摘 要 目的：使用网状Meta分析系统评价胰高血糖素样肽1受体激动剂（GLP-1 RAs）类降糖药对2型糖尿病（T2DM）患者头疼和眩晕的影响。方法：系统检索Medline、Embase、Clinical trials和Cochrane数据库中（截止2017年6月23日）比较GLP-1 RAs与传统降糖药或安慰剂对头疼和眩晕发生风险影响的随机对照试验（RCT）,采用贝叶斯网状Meta分析对纳入的研究进行分析。结果：共纳入100项RCTs,包括15种干预措施：8种GLP-1 RAs类降糖药（艾塞那肽、艾塞那肽缓释剂、利拉鲁肽、利西拉来、他司鲁肽、阿必鲁肽、杜拉鲁肽、索玛鲁肽）、安慰剂、2种二肽基肽酶-4（DPP-4）抑制剂（西格列汀和维格列汀）和4种传统降糖药（胰岛素、二甲双胍、磺脲类、噻唑烷二酮类）。网状Meta分析结果显示：与胰岛素相比,艾塞那肽（OR=1.35,95%CI：1.13~1.60）、利拉鲁肽（OR=1.35,95%CI：1.12~1.62）、利西拉来（OR=1.59,95%CI：1.22~2.06）和他司鲁肽（OR=1.78,95%CI：1.33~2.37）致T2DM患者发生头疼的风险增加;与安慰剂、胰岛素及噻唑烷二酮相比,艾塞那肽和利拉鲁肽显著增加了眩晕发生的风险（OR的取值范围为1.56~2.56）。此外,后验概率显示,致T2DM患者发生头疼风险最高的前三位为艾塞那肽缓释剂、二甲双胍、他司鲁肽;致T2DM患者发生眩晕风险最高的前三位为利拉鲁肽、利西拉来和艾塞那肽。结论：艾塞那肽缓释剂和他司鲁肽显著增加了头疼的发生风险,利拉鲁肽显著增加了眩晕的发生风险,但仍建议开展相应的大型前瞻性研究加以验证。     

高密度脂蛋白与载脂蛋白A1、低密度脂蛋白与载脂蛋白B的相关性分析

目的对高密度脂蛋白与载脂蛋白A1、低密度脂蛋白与载脂蛋白B之间的相关性进行分析探讨。方法随机抽取在2010年1月～2012年5月间在本院进行体检的500名受检者,对其进行血清高密度脂蛋白(HDL-C)、低密度脂蛋白(LDL-C)、载脂蛋白A1(apoA1)、载脂蛋白B(apoB)测定,并按照三酰甘油(TG)水平的不同进行分组,分析HDL-C与apoA1、LDL-C与apoB之间的相关性。结果在TG水平小于10.00mmol/L时,HDL-C与apoA1、LDL-C与apoB之间存在明显的相关性,在TG水平大于10.00mmol/L时,HDL-C与apoA1、LDL-C与apoB不具有明显的相关性。结论在一定条件下,HDL-C与apoA1、LDL-C与apoB存在比较明显的相关性,这将对临床诊断与治疗评价产生重要意义,值得关注。     

Doxorubicin-Bound Albumin Nanoparticles Containing a TRAIL Protein for Targeted Treatment of Colon Cancer

Purpose

We developed a new nanoparticle formulation comprised of human serum albumin (HSA) for co-delivery of doxorubicin (Dox) and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) with the goal of apoptotic synergy in the treatment of colon cancer.

Methods

TRAIL (0.2, 0.4, 1.0%)- and Dox-loaded HSA nanoparticles (TRAIL/Dox HSA NPs) were prepared by using the nab^TM technology. Morphological and physicochemical characterizations were investigated by dynamic light scattering and transmission electron microscopy. Synergistic cytotoxicity, apoptotic activity, and potential penetration into mass tumor were determined in HCT116 cell-based systems. Furthermore, antitumor efficacy and tumor targeting were also investigated.

Results

TRAIL/Dox HSA NPs were uniformly spherical with sizes of 60?~?120 nm. The encapsulation efficacy of Dox and TRAIL was 68.9–77.2% and 80.4–86.0%, respectively. TRAIL 1.0%/Dox HSA NPs displayed the best inhibition of HCT116 colon cancer cells; inhibition was 6 times higher than achieved with Dox HSA NPs. The TRAIL 1.0%/Dox HSA NPs formulation was studied further. Flow cytometry analysis and TUNEL assay revealed that TRAIL 1.0%/Dox HSA NPs had markedly greater apoptotic activity than Dox HSA NPs. In HCT116 tumor-bearing BALB/c nu/nu mice, TRAIL 1.0%/Dox HSA NPs had significantly higher antitumor efficacy than Dox HSA NPs (tumor volume; 933.4 mm³ vs. 3183.7 mm³, respectively). TRAIL 1.0%/Dox HSA NPs penetrated deeply into tumor masses in a HCT116 spheroid model and localized in tumor sites after tail vein injection.

Conclusions

Data indicate that TRAIL 1.0%/Dox HSA NPs offer advantages of co-delivery of Dox and TRAIL in tumors, with potential synergistic apoptosis-based anticancer therapy.