摘要：肿瘤微环境中的血管生成是肿瘤细胞对放化疗不敏感的主要原因.在本项研究中,我们设计了一种微环境响应型的纳米颗粒,利用ZrMOF的分解产物抑制肿瘤细胞中的PI3K/AKT/mTOR/VEGF通路,从而克服A549R细胞对顺铂的耐药性.我们将顺铂包裹在Zr-MOF中,并在表面修饰BSA,形成了CDDP@Zr-MOF-BSA纳米复合体,该复合体在肿瘤微环境中有良好的响应性,有助于在肿瘤区域蓄积,展现出卓越的血管生成抑制能力,并能明显降低药物的外排.此外,CDDP@Zr-MOFBSA能显著抑制多药耐药相关蛋白1(MRP1)的表达,从而逆转A549R细胞的耐药性.总体而言,CDDP@Zr-MOF-BSA对A549R有细胞毒性,能抑制肿瘤微环境中的血管生成,最终有效提高顺铂耐药肿瘤的治疗效果.CDDP@Zr-MOF-BSA为放化疗治疗耐药肿瘤提供了一种多功能协同的方法.

摘要：目的验证盐酸阿比朵尔在中国自然获得流行性感冒受试者中的临床疗效并观察其安全性和耐受性。方法采用随机、双盲和安慰剂对照的多中心临床试验设计。共入组232人,入组条件为年龄≥18岁,≤65岁;发热≥37.8℃;符合流感疑似病例诊断标准;出现症状后不超过36h。合格的受试者随机接受盐酸阿比朵尔200mg或安慰剂治疗,每日3次,共5d。结果疗效分析总体为PPi,即指按规定服用药物并完成所有随访且实验室检查证明为流感病毒感染的病例,试验组59例,对照组66例。两组疾病缓解率经生存分析Logrank检验,试验组缓解率高于对照组。试验组疾病持续时间中位数为72.00h(95%可信区间为66.00～78.00h),对照组疾病持续时间中位数为96.00h(95%可信区间为87.46～104.54h),两组比较差异有显著性(P=0.0083)。试验组症状总分下降值的曲线下面积中位数为780.00(95%可信区间为700.77～859.23),对照组中位数为684.00(95%可信区间为559.81～808.19),两组经Wilcoxon检验差异有显著性(P=0.005)。共有232例可用于安全性分析熏试验组113例,对照组119例。共有20例不良事件可能与研究药物有关,其中试验组7例(6.19%),对照组13例(10.9%),两组间差异无显著性(P=0.245)。不良反应主要为消化系统症状和血清转氨酶升高。结论盐酸阿比朵尔在流感发病?

摘要：Background Chronic kidney disease （CKD） is a common disorder associated with multiple adverse clinical consequences,especially cardiovascular risk and end-stage renal disease.A recent national survey demonstrated that CKD has become a leading health problem in *** is an urgent need to implement an in-depth investigation of the CKD burden and also to explore underlying mechanisms of CKD progression and it association with adverse *** The Chinese Cohort Study of Chronic Kidney Disease （C-STRIDE） is the first national CKD cohort in *** will enroll approximately 3 000 pre-dialysis CKD patients aged between 18 and 74 years and follow-up for at least 5 ***,anthropometric measures,laboratory tests,and biomaterials will be collected at baseline and *** principal clinical outcomes of the C-STRIDE consist of renal disease events,cardiovascular events,and *** on the longitudinal clinical data and biomaterials,the risk factors with CKD progression and other outcomes will be analyzed,and candidate markers and predicted models will be *** The C-STRIDE would provide important evidence for underlying mechanisms of CKD progression,valuable information for clinical guidelines,and healthcare policies in China.

摘要：An essential step for cancer vaccination is to break the immunosuppression and elicit a tumor-specific immunity.A major hurdle against cancer therapeutic vaccination is the insufficient immune stimulation of the cancer vaccines and lack of a safe and efficient adjuvant for human *** discovered a novel cancer immunostimulant,trichosanthin(TCS),that is a clinically used protein drug in China,and developed a well-adaptable protein-engineering method for making recombinant protein vaccines by fusion of an antigenic peptide,TCS,and a cell-penetrating peptide(CPP),termed an"allin-one"vaccine,for transcutaneous cancer *** TCS adjuvant effect on antigen presentation was investigated and the antitumor immunity of the vaccines was investigated using the different tumor *** vaccines were prepared via a facile recombinant *** vaccines induced the maturation of DCs that subsequently primed CD8^(+)T *** TCS-based immunostimulation was associated with the STING *** general applicability of this genetic engineering strategy was demonstrated with various tumor antigens(i.e.,legumain and TRP2 antigenic peptides)and tumor models(i.e.,colon tumor and melanoma).These findings represent a useful protocol for developing cancer vaccines at low cost and time-saving,and demonstrates the adjuvant application of TCSdan old drug for a new application.

摘要：To get an optimal product of orthopaedic implant or regenerative medicine needs to follow trialand-error analyses to investigate suitable product’s material,structure,mechanical properites *** whole process from in vivo tests to clinical trials is expensive and *** model is seen as a useful analysis tool to make the product development.A series of models for simulating tissue engineering process from cell attachment to tissue regeneration are *** challenging is that models for simulating tissue engineering processes are developed *** cell to tissue regeneration,it would go through blood injection after moving out the defect;to cell disperse and attach on the scaffold;to proliferation,migration and differentiation;and to the final part-becoming mature *** paper reviewed models that related to tissue engineering process,aiming to provide an opportunity for researchers to develop a mature model for whole tissue engineering *** article focuses on the model analysis methods of cell adhesion,nutrient transport and cell proliferation,differentiation and migration in tissue *** cell adhesion model,one of the most accurate method is to use discrete phase model to govern cell movement and use Stanton-Rutland model for simulating cell *** for nutrient transport model,numerical model coupling with volume of fluid model and species transport model together is suitable for predicting nutrient transport *** cell proliferation,differentiation and migration,finite element method with random-walk algorithm is one the most advanced way to simulate these *** of the model analysis methods require further experiments to verify the accuracy and *** to the lack of technology to detect the rate of nutrient diffusion,there are especially few researches on model analysis methods in the area of blood ***,there is still a lot of work to be done in the resea

摘要：Objective： To evaluate the effects of repairing rabbit radial defects with polyester/tricalcium phosphate scaffolds prepared by rapid prototyping technology loaded with bovine bone morphogenetic protein （ bBMP）, and find new carriers for growth factors. Methods： Polyester/tricalcium phosphate scaffolds prepared by rapid prototyping technology loaded with and without bovine BMP were used to repair the 15 mm radial defect in rabbit. Then the results of radiography, histology, scaffolds degrade rates and bone mineral density （BMD） were appraised to examine the effects at the 12th week. Results ： At the 12th week postoperatively, all defects treated with bBMP were radiographically repaired. No radius implanted polyester/tricalcium phosphate scaffolds without bBMP showed radiographic and histological union. At experimental groups, longitudinal alignment of lamellar structure was observed histologically at the 12th week,indicating that remodeling of regenerated bone was complete in different degree. Of the three experimental groups, the bony regeneration and remodeling of callus in poly lactide-co-glycolide/tricalcium phosphate （PLGA/ TCP） group was the best. The BMD values were beyond 70% of normal value at the 12th week while the PLGA/ TCP scaffolds group was the highest, and no abnormalities were observed in the surrounding soft tissue in all groups. Conclusions - Polyester/tricalcium phosphate scaffolds prepared by rapid prototyping technology loaded with bovine BMP can repair a 15 mm radial defect of rabbit. As for the results, the PLGA/TCP scaffold is ideal and better than poly L-lactide-co-D, L-lactide （ PDLLA/TCP ） scaffold, but the ploy L-lactic acid （PLLA/TCP） is not so good for its low degradation rates.

摘要：目的构建含人粘附分子-2(ICAM-2)启动子的人补体调节蛋白CD59重组基因,并将其用于异种器官移植转基因。方法利用PCR方法从人血基因组扩增得到ICAM-2启动子、CD59基因的第一内含子片段,经电泳分离、切胶回收纯化得到上述片段,分别双酶、单酶切这两条片段,纯化回收备用;双酶切pcDNA3-CD59真核表达载体,经电泳分离、切胶回收纯化得到不含病毒启动子、含筛选基因Neo的一段pcDNA3-CD59cDNA作为载体序列;ICAM-2启动子片段先与载体进行定向克隆连接反应后转化细菌,阳性转化菌质粒抽提及酶切鉴定,得到pcDNA3-ICAM2-CD59质粒;再单酶切此质粒,纯化该载体与CD59第一内含子片段连接,转化细菌、抽提质粒,用脂质体将该质粒转染猪血管内皮细胞,流式细胞仪检测CD59蛋白表达。结果得到pcDNA3-Enhancer-ICAM2-CD59质粒,以EcoRⅠ消化此重组质粒,产生5.5及0.5kb两片段;以HindⅢ消化重组质粒,得到5.45及0.55kb两片段,以KpnⅠ/HindⅢ双酶切质粒时,出现5.0、0.55、0.4kb3条片段,对插入子分别进行测序,上述结果完全符合设计要求及正确序列。流式细胞仪检测重组基因表达阳性。结论含人ICAM-2启动子的CD59重组基因表达载体获得成功,该重组基因构建成功为转基因应用奠定了基础。

摘要：Tissue engineering is an interdisciplinary field promising new therapeutic means for replacing lost or severely damaged tissues or organs. However, the fabrication of complex engineered tissues has been hampered due to the lack of vascularization to provide sufficient blood supply after implantation. In this article, we propose using rapid prototyping technology to prefabricate a scaffold with an inside hollowed vascular system including an arterial end, a venous end and capillary networks between them. The scaffold will be ''printed'' layer by layer. When printing every layer, a ''low-melting point'' material will be used to form a blood vessel network and a tissue-specific material will be used outside it. Hereafter the ‘low-melting point’ material will be evacuated by vaporization to ensure a hollowed vessel network. Then the inside hollowed capillary network can be endothelialized by using autologous endothelial cells in a cycling bioreactor while the outside material can be embedded with tissue-special cells. In the end, the new vascularized autologous grafts could be transferred to the defect site by using microsurgical techniques to connect the grafts with the host artery and vein. The strategy would facilitate construction of complex tissue engineering if the hypothesis proved to be practical.

摘要：Malaria still threatens global health seriously *** the current discoveries of antimalarials are almost totally focused on single mode-of-action inhibitors,multi-targeting inhibitors are highly desired to overcome the increasingly serious drug ***,we performed a structure-based drug design on mitochondrial respiratory chain of Plasmodium falciparum and identified an extremely potent molecule,RYL-581,which binds to multiple protein binding sites of *** simultaneously(allosteric site of type Ⅱ NADH dehydrogenase,Q_(o) and Q_(i) sites of cytochrome bc_(1)).Antimalarials with such multiple targeting mechanism of action have never been reported ***-581 kills various drug-resistant strains in vitro and shows good solubility as well as in vivo *** structurebased strategy for designing RYL-581 from starting compound may be helpful for other medicinal chemistry projects in the future,especially for drug discovery on membrane-associated targets.

摘要：The repair of osteochondral defects is one of the major clinical challenges in ***-established osteochondral tissue engineering methods have shown promising results for the early treatment of small ***,less success has been achieved for the regeneration of large defects,which is mainly due to the mechanical environment of the joint and the heterogeneous nature of the *** this study,we developed a multi-layered osteochondral scaffold to match the heterogeneous nature of osteochondral tissue by harnessing additive manufacturing technologies and combining the established art laser sintering and material extrusion *** developed scaffold is based on a titanium and polylactic acid matrix-reinforced collagen“sandwich”composite *** microstructure and mechanical properties of the scaffold were examined,and its safety and efficacy in the repair of large osteochondral defects were tested in an ovine condyle *** 12-week in vivo evaluation period revealed extensive and significantly higher bone in-growth in the multi-layered scaffold compared with the collagen–HAp scaffold,and the achieved stable mechanical fixation provided strong support to the healing of the overlying cartilage,as demonstrated by hyaline-like cartilage *** histological examination showed that the regenerated cartilage in the multi-layer scaffold group was superior to that formed in the control *** genes such as aggrecan and collagen-II were upregulated in the scaffold and were higher than those in the control *** findings showed the safety and efficacy of the cell-free“translation-ready”osteochondral scaffold,which has the potential to be used in a one-step surgical procedure for the treatment of large osteochondral defects.