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1. chinaXiv:202107.00013 [pdf]

On the origin of SARS-CoV-2–The blind watchmaker argument

Chung-I Wu; Haijun Wen; Jian Lu; Xiao-dong Su; Alice C. Hughes; Weiwei Zhai; Chen Chen; Hua Chen; Mingkun Li; Shuhui Song; Zhaohui Qian; Qihui Wang; Bingjie Chen; Zixiao Guo; Yongsen Ruan; Xuemei Lu; Fuwen Wei; Li Jin; Le Kang; Yongbiao Xue
Subjects: Biology >> Virology

In the comparison with SARS-CoV of 2003, SARS-CoV-2 is extremely well adapted to the human populations and its adaptive shift from the animal host to humans must have been even more extensive. By the blind watchmaker argument, such an adaptive shift can only happen prior to the onset of the current pandemic and with the aid of step-by-step selection. In this view, SARS-CoV-2 could not have possibly evolved in an animal market in a big city and even less likely in a laboratory. Discussions of the origin of SARS-CoV-2 need to factor in the long process of adaptive shift and some models have indeed advanced in that direction.

submitted time 2021-07-17 Hits482Downloads165 Comment 0

2. chinaXiv:202107.00008 [pdf]

GT198蛋白是抗癌化药和抗癌草药的靶点

庞峻峰; 高洁; 张立勇; Nahid F. Mivechi ; 柯蓝
Subjects: Medicine, Pharmacy >> Pharmacology

肿瘤血管生成是癌症的一个特征。一些抗血管生成的抗癌药物已被证明临床有疗效。我们之前的研究显示,在包括口腔癌在内的人类实体瘤中,GT198 蛋白(基因符号PSMC3IP,又称为Hop2)是一个诱导血管生成的癌蛋白。本研究结果表明,十几种临床抗癌化疗药物,和几种临床成功的抗癌草药,都能直接抑制GT198蛋白靶点。GT198是一个能与DNA结合的DNA修复蛋白。利用体外DNA结合法检测GT198活性,我们测试了129个美国NCI收集的临床抗癌化疗药物。发现体外直接抑制GT198的化药包括但不限于米托蒽醌、多柔比星(阿霉素)、紫杉醇、依托泊苷、放线菌素D和伊马替尼(格列卫)。紫杉醇和依托泊苷具有较高的结合亲和力,而多柔比星由于竞争性抑制GT198,具有较高的结合效力。由于GT198与DNA拓扑异构酶有蛋白序列同源性,而DNA拓扑异构酶是过去认为的药物靶点,因此,GT198蛋白很可能是个以前未被认知的药物新靶点。为了寻求更高效的GT198抑制剂,我们进一步测试了几种抗癌草药的提取物。发现具有高亲和力和高效力的阳性抑制草药都是临床上已经有成功历史的抗癌草药,包括牙买加的多香果(Allspice)、中国的皂角刺(Gleditsia sinensis L.),和厄瓜多尔的BIRM。我们使用有机化学方法对多香果进行了部分纯化,证明用GT198为靶标,以体外DNA结合法追踪测活,可以高效快速纯化天然产物。综上表明,此项研究揭示了GT198是多种抗癌化药的新靶点。这项研究还提供了一个鉴定化合物与纯化天然产物的优异药物靶标。特别关键的是,这项研究为快速分离高效低毒的抗癌中草药提供了绝佳机会。

submitted time 2021-07-12 Hits3252Downloads113 Comment 0

3. chinaXiv:202106.00110 [pdf]

利用一对多尿液蛋白质组比较为发热待查提供线索

赵晨阳; 魏利龙; 魏静; 高友鹤
Subjects: Biology >> Biochemistry

发热待查是指不明原因的发热,尽管医疗诊断技术在不断发展,但是发热待查仍旧是亟待解决的难题。尿液是机体排泄代谢废物的一种途径,由于不受到稳态调节机制的影响,尿液能反映机体产生的微小变化,比血液更早期、更敏感。在本研究中,我们对收集的尿液样本采用一对多的尿液蛋白质组比较方法,即一个病人和一组健康人样本对比分析的方法,旨在通过差异蛋白来寻找与疾病相关的生物学通路,为发热待查的临床诊断提供线索和依据。分析结果表明,差异蛋白富集到的生物学通路与发热有关,尿蛋白质组能够提供病人和健康人的区别;同时一对多的研究方法能为发热待查患者提供个性化的线索,也是未来探索病人未知疾病的一个方法。

submitted time 2021-06-25 Hits3226Downloads165 Comment 0

4. chinaXiv:202105.00077 [pdf]

二维光学刺激下的视觉感知定律

祝锐; 刘玉红; 王体春; 陈龙聪; 谢正祥
Subjects: Computer Science >> Computer Application Technology
Subjects: Engineering and technical science >> Optical Engineering

人类对刺激量的感知分为数量感知和质量感知。无论是韦伯-费克纳(Weber-Fechner)的对数感觉定律还是史蒂文斯(Stevens)的幂函数感觉定律,都是关于感觉量与一维亮度刺激之间定量关系的定律。图像属于具有二维亮度分布特征的刺激量。本文研究的是二维亮度刺激的质量的感知,即二维亮度刺激质量好坏程度的感知。好坏程度是一个模糊的心理学概念,因此我们需要用模糊数学的方法来量化图像视觉感知质量的好坏程度,即建立一个模糊隶属函数PQ来定量表示图像视觉质量的好与坏的程度。

submitted time 2021-05-24 Hits2877Downloads292 Comment 0

5. chinaXiv:202105.00003 [pdf]

Sepsis prediction via the clinical data integration system in the ICU

Chen, Qiyu; Li, Ranran; Lin, Zhizhe; Lai, Zhiming; Xue, Peijiao; Jiang, Jingfeng; Lu, Wenlian; Li, Lei; Tang, Yaoqing
Subjects: Medicine, Pharmacy >> Clinical Medicine

Sepsis is an essential issue in critical care medicine, and early detection and intervention are key for survival. We established the sepsis early warning system based on a data integration platform that can be implemented in ICU. The sepsis early warning module can detect the onset of sepsis 5 hours proceeding, and the data integration platform integrates, standardizes, and stores information from different medical devices, making the inference of the early warning module possible. Our best early warning model got an AUC of 0.9833 in the task of detect sepsis in 4 hours proceeding on the open-source database. Our data integration platform has already been operational in a hospital for months.

submitted time 2021-05-07 Hits5919Downloads274 Comment 0

6. chinaXiv:202104.00020 [pdf]

Bacterial and viral therapies of cancer background, mechanism and perspective

Qinglin Dong, Xiangying Xing
Subjects: Medicine, Pharmacy >> Preclinical Medicine

Bacterial and viral therapies of cancer are highly promising, yet their mechanisms are incompletely understood, hindering their improvement and application. In this paper, We (1) review briefly the genesis and progress of bacterial and viral therapies of cancer, (2) compare and evaluate the proposed mechanisms of bacterial and viral therapies of cancer and present the unifying mechanism that bacteria/viruses stimulate cancer cells to produce antibacterial/antiviral proteins, which also serve as the responsive cancer antigens triggering host anticancer immune response, and (3) provide a perspective on the exploitation of non-human and non-animal bacteria and viruses, particularly protist-infecting bacteria and viruses and bacterial virus (bacteriophage/phage), for cancer treatment and prevention.

submitted time 2021-04-29 Hits5069Downloads412 Comment 0

7. chinaXiv:202103.00122 [pdf]

应用改良No-touch技术建立兔颈总动脉-颈外静脉内瘘模型

刘振; 王晓禾; 王加英; 张元元; 侯国存
Subjects: Medicine, Pharmacy >> Preclinical Medicine

目的 探索应用改良No-touch技术建立兔颈总动脉-颈外静脉内瘘模型的可能性。 方法 2021年02月08日至2021年02月22日,将10只雄性新西兰兔随机等分为实验组与假手术组。实验组在内瘘手术时不剥离静脉周围组织,即改良No-touch技术处理颈外静脉,建立颈总动脉-颈外静脉内瘘。假手术组探查到血管后不吻合血管。术后14 d使用CDU评估内瘘血管内径及血流频谱变化、苏木精 - 伊红(H-E)染色观察动静脉内瘘建立后内膜增生情况,并取兔颈外静脉血行血气分析。 结果 实验组兔均顺利成功完成动静脉内瘘手术,成功率100%。术后14 d CDU评估结果显示实验组兔颈外静脉较假手术组明显扩张(P=0.016)、收缩期峰值流速(PSV)明显增加(P=0.015)。在实验组兔内瘘动脉及流出道静脉观察到“双向血流”频谱,提示血流为螺旋层流。H-E染色结果显示,实验组兔颈外静脉内弹力膜破坏、内膜厚度较假手术组明显增加(P<0.001)。实验组兔颈外静脉血PO2较假手术组明显升高(P=0.006)。结论 应用改良No-touch技术可成功建立兔颈总动脉-颈外静脉内瘘,成功率高,重复性好,为进一步研究改良No-touch技术在动静脉内瘘手术中的应用提供理想的动物模型。

submitted time 2021-03-09 Hits3649Downloads521 Comment 0

9. chinaXiv:202101.00036 [pdf]

Targeting pan-tumor antigens to activating Fcγ receptors generates a novel dendritic cell tumor vaccine

Sheng, Hui; Wnag, Pan; Zhang, Guoxiu; Zhang, Xiao; Li, Zhongjun; Zhao, Zhihui
Subjects: Medicine, Pharmacy >> Preclinical Medicine

Objective: Therapeutic tumor vaccines are eagerly awaited in clinic by patients with high expectations; however, very few clinically successful tumor vaccine has been developed thus far, and there remains no consensus on the generation of tumor vaccines. We hypothesized that targeted delivery of pan-tumor antigens instead of individual tumor-associated antigen (TAA) to dendritic cells via the activating receptor endocytic pathway (AREP) would provide an alternative avenue to develop potent personalized tumor vaccines. Methods: We first prepared biotin-tagged tumor antigens (B-TAgs) with mouse CT26. WT colorectal cancer cells by exploiting metabolic glycan labeling and bioorthogonal reaction methods; then, we prepared a bifunctional fusion protein containing streptavidin and a mouse IgG2a Fc fragment (SA-Fc), in which streptavidin was used for conjugation with B-TAgs, and Fc for mediating the interaction with the Fcγ receptor. Finally, conjugates (Fc-TAgs) of SA-Fc with B-TAgs were prepared based on affinity-guided noncovalent reaction. The phenotype of Fc-TAgs pulsed bone marrow-derived dendritic cells (BMDCs) was examined by flow cytometry. The therapeutic effects of Fc-TAgs pulsed BMDCs were observed in an established mouse CT26. WT colorectal cancer model. Results: The prepared B-TAgs covers almost all glycosylated tumor antigens. SA-Fc fusion protein exhibits biotin-binding activity as a homodimer. SA-Fc can effectively conjugate with B-TAg at a mixing ratio of 1:96 (w/w). Data of flow cytometry revealed that on Fc-TAgs pulsed BMDCs, the expression levels of surface molecules, such as CD80 and MHC II, were greatly increased. In the established murine colorectal cancer model, combination treatments with Fc-TAgs pulsed BMDCs and PD-1 blockade achieved significant therapeutic effects. Limitations: The strategy we proposed for the preparation of personalized tumor vaccine requires that the tumor be surgically removed from the patient. The rationality and validity of this strategy need to be proven by more preclinical investigations. Conclusions: The novel strategy we proposed circumvents the necessities for neoantigen prediction and provides an alternative pathway to establish a flexible system for the preparation of personalized dendritic cell tumor vaccines. In the setting of checkpoint blockade-based immunotherapy, a novel DCV would improve antitumor immunity and benefit the eradication of tumor residues within the body of the cancer patients.

submitted time 2021-01-07 Hits6652Downloads810 Comment 0

10. chinaXiv:202011.00119 [pdf]

模型引导下免疫检查点抑制剂的研发

郑冠濠; 王琛瑀; 焦正
Subjects: Medicine, Pharmacy >> Pharmacology

免疫检查点抑制剂类药物作为一种新型的抗肿瘤治疗手段,以其对多种肿瘤卓越的疗效及良好的安全性得到广泛认可。基于定量药理学的发展应运而生的模型引导的药物研发(Model-informed Drug Development, MIDD),能加速新药临床试验的进程,提高新药研究过程中决策的正确率,尤其是对研发难度较大而需求甚广的免疫检查点抑制剂类新药取得了成功。本文主要以帕博利珠单抗为例,阐述MIDD方法在免疫检查点抑制剂研发过程中的具体应用,包括研发早期有效给药方案的拟定,研发晚期评估临床疗效和验证给药方案的可行性,再至上市后给药方案的再评估及变更,为MIDD指导抗肿瘤新药的研发提供参考。

submitted time 2020-11-24 Hits5803Downloads747 Comment 0

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