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1. chinaXiv:202104.00020 [pdf]

Bacterial and viral therapies of cancer background, mechanism and perspective

董庆霖
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 and present the unifying mechanism that bacterial and viral therapies of cancer mainly take advantage of the immune response of cancer cells to bacteria and viruses and the ability of host immune system to recognize and eliminate the responsive cancer cells, 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), for cancer therapy.

submitted time 2021-04-06 Hits143Downloads61 Comment 0

2. 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 Hits573Downloads172 Comment 0

3. 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 Hits2778Downloads455 Comment 0

4. chinaXiv:202002.00082 [pdf]

ACE2 shedding and furin abundance in target organs may influence the efficiency of SARS-CoV-2 entry

Yuanchen Ma; Yinong Huang; Tao Wang; Andy Peng Xiang; Weijun Huang
Subjects: Medicine, Pharmacy >> Preclinical Medicine

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a recently identified lineage B coronavirus, causing rapid worldwide outbreak of Corona Virus Disease 2019 (COVID-19). Despite genetically closed to SARS-CoV, SARS-CoV-2 seems to possess enhanced infectivity and subtle different clinical features, which may hamper the early screening of suspected patients as well as the control of virus transmission. Unfortunately, there are few tools to predict the potential target organ damage and possible clinical manifestations caused by such novel coronavirus. To solve this problem, we investigate the potential host cell entry mechanisms of SARS-CoV-2 through bioinformatics. Using the online single-cell sequence datasets, we analyze the expression of major receptor in host cells that mediates the virus entry, including angiotensin converting enzyme 2 (ACE2), and its co-expressed membrane endopeptidases. The results indicated the differential expression of ADAM10 and ADAM17 might contribute to the ACE2 shedding and affect the membrane ACE2 abundance. We further confirm a putative furin-cleavage site reported recently in the spike protein of SARS-CoV-2, which may facilitate the virus-cell fusion. Based on these findings, we develop a novel approach that comprehensively analyzed the virus receptor expression, ACE2 shedding, membrane fusion activity, virus uptake and virus replication to evaluate the infectivity of SARS-CoV-2 to different human organs. Our results indicate that, in addition to airway epithelia, cardiac tissue and enteric canals are susceptible to SARS-CoV-2 as well.

submitted time 2020-02-27 Hits48498Downloads5178 Comment 0

5. chinaXiv:202002.00075 [pdf]

2019年新型冠状病毒导致的致命肺渗漏的病理生理学机制和防治策略

Chen, Sifeng
Subjects: Medicine, Pharmacy >> Preclinical Medicine

自2019年12月爆发以来,2019年新型冠状病毒已在全球造成2596人死亡,并且有超过11,000名患者仍处于严重状况。该病毒和由该病毒引起的医疗状况被命名为SARS-CoV-2和COVID-19。虽然已经广泛应用了抗病毒、对症和功能支持性疗法,每天仍有100多名患者死于该病毒感染。COVID-19最常见的致命并发症是急性呼吸窘迫综合征(ARDS)。SARS-CoV-2在世界范围内的大流行可能仍然存在。其它病毒感染引起的肺炎亦可导致ARDS,出现类似的危重情形,这些病毒包括如非典型的急性呼吸系统综合症(SARS)、中东呼吸综合征(MERS)和流感病毒引起的肺炎。因此,制定更有效的降低病毒所致的ARDS死亡率的策略,不但是当前抗新冠疫情的迫切需要,也是全球范围内降低病毒性肺炎死亡率的长期需要。ARDS曾被称为湿肺,血管泄漏导致的肺水肿是其最重要的病理特征之一,重型COVID-19的临床表现和胸部计算机断层扫描图像特征(白肺)符合ARDS。确定水肿液从何处及如何渗漏到肺部,是制定基于机制的预防和阻止水从肺毛细管向肺间质渗漏的策略,降低湿肺死亡率的关键。对于轻度和中度病例,非类固醇消炎药,如用于风湿性关节炎的药物,可能有助于防止和减少这种漏水。免疫抑制剂(如西罗莫司和巨蜥)可能使病毒感染、免疫反应和非免疫炎症造成的损伤高峰时间错开,从而降低肺漏水程度,防止危及生命情况出现。使用清火中草药可能也有抗炎用。对于严重病例,血液透析可能是消除大多数炎症介质和细胞毒性物质的有效策略。

submitted time 2020-02-25 Hits19575Downloads1867 Comment 0

6. chinaXiv:202002.00027 [pdf]

伊马替尼治疗新型冠状病毒肺炎引起的急性呼吸窘迫综合征

李翀
Subjects: Medicine, Pharmacy >> Preclinical Medicine

伊马替尼(Imatinib),酪氨酸激酶抑制剂,是一种小分子蛋白激酶抑制剂,临床用于治疗慢性髓性白血病和恶性胃肠道间质肿瘤。急性呼吸窘迫综合征(ARDS)是肺部的一种炎症过程,以低氧血症为显著特征的临床综合征。越来越多的证据显示,伊马替尼能有效缓解ARDS。

submitted time 2020-02-17 Hits5790Downloads1000 Comment 0

7. chinaXiv:201806.00136 [pdf]

术前血清白蛋白水平对非肌层浸润性膀胱癌患者行经尿道膀胱肿瘤电切术的预后价值

张玥; 李飞; 杨帆; 曾文利; 林昊; 翟启良; 苏明强; 陈自豪; 谭万龙
Subjects: Medicine, Pharmacy >> Preclinical Medicine

目的:明确术前血清白蛋白水平能否作为非肌层浸润性膀胱癌(NMIBC)患者经尿道膀胱肿瘤电切术(TURBT)的生存预后指标。方法纳入2007年1月~2012年4月间在本院初治诊为NMIBC,并行TURBT术治疗,有完整临床资料及随访数据的216名膀胱癌患者。将纳入患者根据术前血清白蛋白水平分为低血清白蛋白组(<40 g/L)和正常血清白蛋白组(≥40 g/L)。应用Kaplan-Meier 模型评估两组患者生存情况,并用Cox比例风险模型对总体生存率(OS)进行单、多因素分析。结果216 例NMIBC患者中,低血清白蛋白组共82(39%)例,正常血清白蛋白组共127(61%)例。Kaplan-Meier分析结果显示低血清白蛋白组的5年OS低于正常血清白蛋白组(P=0.017)。进一步进行Cox多因素分析以排除干扰因素的影响后发现,术前血清白蛋白水平仍可成为NMIBC电切患者5年OS(HR:3.102,95% CI:1.200~8.020,P=0.020)的独立危险因素。结论术前低血清白蛋白水平的NMIBC电切患者拥有更差的5年OS。对于NMIBC电切患者,术前血清白蛋白水平可作为一项廉价易得且简单有效的生存预后指标。

submitted time 2018-06-15 From cooperative journals:《南方医科大学学报》 Hits2565Downloads1389 Comment 0

8. chinaXiv:201806.00137 [pdf]

实验树鼩心肌缺血再灌注离体模型的构建

杨天睿,; 苗云波; 张荣平; 余锦雯
Subjects: Medicine, Pharmacy >> Preclinical Medicine

目的:建立实验树鼩心肌缺血再灌注离体模型。方法采用Langendorff 离体心脏灌流系统建立实验树鼩心肌缺血再灌注模型,依据不同的停灌和再灌注时间实验分为5组;酶标法测丙氨酸氨基转移酶(ALT),天冬氨酸氨基转移酶(AST)和乳酸脱氢酶(LDH),免疫抑制法测定肌酸激酶MB同工酶(CK-MB)2,3,5-氯化三苯基四唑染色法(TTC)测定切片梗死面积。结果心肌酶学指标和梗死面积检测发现,停灌30 min再灌注30 min组和停灌30 min再灌注60 min组灌流液CK-MB,灌流液LDH,组织ALT,组织CK-MB和组织LDH等指标均显著高于其它3组(P<0.05),但两组间差异无统计学意义(P>0.05)。心电分析发现,停灌30 min再灌注60 min组心率显著低于持续灌注组,停灌15 min 再灌注30 min 组和停灌30 min 再灌注30 min 组(P<0.05),而停灌30 min 再灌注30 min 组心率与持续灌注组和停灌15 min再灌注30 min组差异无统计学意义(P>0.05),停灌30 min再灌注30 min组的离体心脏平均心率更接近于实验树鼩的生理指标。结论实验树鼩心肌缺血再灌注离体Langendorff模型构建成功,停灌30 min再灌注30 min模型效果最好。

submitted time 2018-06-15 From cooperative journals:《南方医科大学学报》 Hits2403Downloads1330 Comment 0

9. chinaXiv:201806.00138 [pdf]

Rosai-Dorfman disease in the larynx: report of a case and literature review

XU Xia; DENGWenting; HUANG Chengzhi; WANG Jian
Subjects: Medicine, Pharmacy >> Preclinical Medicine

Rosai-Dorfman病是一种发生在淋巴结或结外组织的良性组织细胞增生性病变,而发生在喉部的结外Rosai-Dorfman病例及其罕见,其病变特征不明显,缺乏典型的发热及淋巴结肿大症状,临床上易误诊为恶性肿瘤,治疗也无标准可循。本文报道1 例喉部Rosai-Dorfman病,应用微创手术加激素治疗,保留了喉功能,取得良好疗效,并结合文献对这一罕见疾病的诊治进行探讨。

submitted time 2018-06-15 From cooperative journals:《南方医科大学学报》 Hits2272Downloads1182 Comment 0

10. chinaXiv:201806.00139 [pdf]

聚乳酸-羟基乙酸共聚物载肝细胞生长因子纳米粒的构建及生物学活性评价

冼文娇; 王雪儿; 张琳
Subjects: Medicine, Pharmacy >> Preclinical Medicine

目的:探究制备聚乳酸-羟基乙酸共聚物(PLGA)纳米粒的优化条件,构建肝细胞生长因子(HGF)纳米粒,评价其包封率、载药量、回收率、释放度和生物学活性。方法采用复乳溶剂挥发法制备牛血清白蛋白(BSA)PLGA纳米粒,通过正交试验设计,以粒径较小,包封率、载药量和回收率较高为考察指标,优化纳米粒的制备条件;选取优化条件制备HGF纳米粒,分别采用BCA试剂盒和HGF-ELISA试剂盒检测BSA纳米粒和HGF纳米粒的包封率、载药量和释放度,通过CCK8增殖实验评价HGF纳米粒的生物活性。结果优化条件下制备的HGF 纳米粒大小均匀,粒径234.4±4.8 nm,包封率(77.75±3.04)%,回收率(49.33±9.34)%,体外释放度曲线表现为先突释,后缓释;HGF纳米粒可以促进角质形成细胞的增殖。结论复乳溶剂挥发法-优化条件下制备的HGF纳米粒具有较高包封率,良好的缓释效果和生物学活性。

submitted time 2018-06-15 From cooperative journals:《南方医科大学学报》 Hits2355Downloads1245 Comment 0

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