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Combination therapy with oncolytic virus and t cells or mRNA vaccine amplifies antitumor effects

Signal transduction and targeted therapy 2024年第6期9卷 2655-2668页

作者： rao Fu Ruoyao Qi Hualong Xiong Xing Lei Yao Jiang Jinhang He Feng Chen Liang Zhang Dekui Qiu Yiyi Chen Meifeng Nie Xueran Guo Yuhe Zhu Jinlei Zhang Mingxi Yue Jiali Cao Guosong Wang Yuqiong Que Mujing Fang Yingbin Wang Yixin Chen tong Cheng Shengxiang Ge Jun Zhang Quan Yuan tianying Zhang Ningshao Xia State Key Laboratory of Vaccines for Infectious Diseases Xiang An Biomedicine LaboratoryDepartment of Laboratory MedicineSchool of Public Health&School of Life SciencesXiamen UniversityXiamen 361102 FujianChina National Institute of Diagnostics and Vaccine Development in Infectious Diseases Xiamen 361102 FujianChina

Antitumor therapies based on adoptively transferred t cells or oncolytic viruses have made significant progress in recent years,but the limited efficiency of their infiltration into solid tumors makes it difficult to achieve desired antitumor effects when used *** this study,an oncolytic virus(rVSV-LCMVG)that is not prone to induce virus-neutralizing antibodies was designed and combined with adoptively transferred t *** transforming the immunosuppressive tumor microenvironment into an immunosensitive one,in B16 tumor-bearing mice,combination therapy showed superior antitumor effects than *** occurred whether the OV was administered intratumorally or *** therapy significantly increased cytokine and chemokine levels within tumors and recruited CD8^(+)t cells to the tME to trigger antitumor immune *** with adoptively transferred t cells and subsequent oncolytic virotherapy sensitizes refractory tumors by boosting t-cell recruitment,downregulating the expression of PD-1,and restoring effector t-cell *** offer a combination therapy with greater translational value,mRNA vaccines were introduced to induce tumor-specific t cells instead of adoptively transferred t *** combination of OVs and mRNA vaccine also displays a significant reduction in tumor burden and prolonged *** study proposed a rational combination therapy of OVs with adoptive t-cell transfer or mRNA vaccines encoding tumor-associated antigens,in terms of synergistic efficacy and mechanism.

关键词： transferred rational boosting

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二甲双胍胃肠道不良反应及其新型缓释制剂的临床应用

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中华糖尿病杂志 2024年第7期16卷 827-831页

作者：饶翀崔丽梅肖新华清华大学附属垂杨柳医院内分泌科北京100022 中国医学科学院、北京协和医院内分泌科、国家卫生健康委员会内分泌重点实验室北京100730

二甲双胍广泛应用于2型糖尿病(t2DM)的治疗。二甲双胍的胃肠道反应较为常见,其确切机制尚不明确,可能与其转运蛋白、增加肠道内葡萄糖摄取及乳酸水平、增加肠内胆汁酸池、肠道菌群等相关。二甲双胍缓释片与二甲双胍速释片降糖疗效类似,... 详细信息

二甲双胍广泛应用于2型糖尿病(t2DM)的治疗。二甲双胍的胃肠道反应较为常见,其确切机制尚不明确,可能与其转运蛋白、增加肠道内葡萄糖摄取及乳酸水平、增加肠内胆汁酸池、肠道菌群等相关。二甲双胍缓释片与二甲双胍速释片降糖疗效类似,同时能有效减少胃肠道反应的发生。二甲双胍缓释片的制作工艺主要包括羟丙基甲基纤维素(HPMC)凝胶骨架结构、微孔或单孔渗透泵技术及胃漂浮技术。该文就二甲双胍胃肠道反应及相关机制研究、二甲双胍缓释片的种类、二甲双胍缓释片与二甲双胍速释片疗效对比等进行阐述。

关键词：糖尿病,2型二甲双胍缓释片不良反应

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Influence of local stiffeners and cutout shapes on the vibration and stability characteristics of quasi-isotropic laminates under hygro-thermo-mechanical loadings

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Defence technology（防务技术） 2022年第12期18卷 2107-2124页

作者： t.Rajanna K.S.Subash Chandra K.Venkata rao Department of Civil Engineering B.M.S College of EngineeringBengaluru560019India Research Scholar B.M.S College of EngineeringBengaluru560019India Department of Mechanical Engineering B.M.S Evening College of EngineeringBengaluru560019India Department of Mechanical Engineering Government PolytechnicBagepalli561207India

the perforated stiffened panel is generally found as a sub-component of sophisticated *** fundamental purpose of this panel is to withstand against buckling under complicated loading and environmental ***,an accurate knowledge of critical buckling behaviour of stiffened panels is very much essential for a reliable and lightweight structural *** this paper,the focus is on quasi-laminated panels with different cutout shapes of various sizes and their responses to hygrothermal environments under nonlinearly varying edge loads and is compared with the locally stiffened *** this,the modelling of the panel and stiffener is done by adopting nine-noded heterosis plate elements and three noded beam elements *** stiffener formulation is suitably modified in order to take the torsional effect also into consideration along with the effect of shear ***,the plate and the stiffener elements are treated separately,and then the displacement compatibility is maintained between them by using the transformation *** a given loading and geometric discontinuity,the stress distribution within the perforated panel is highly non-uniform in nature and hence a dynamic approach has been used to calculate buckling loads by adopting two sets of boundary conditions,one set for pre-buckling stress analysis and the second set for buckling *** different quasi-isotropic stacking sequences are deliberated in this work by varying different ply-orientation in each *** study also addresses the effect of various parameters such as nonlinear loads,hygro-thermal loads,cutout size and shapes,position of cutout,stiffener parameters,stacking sequences,thickness of plate and boundary conditions.

关键词： Locally stiffened panels Buckling Vibration Cutouts Heterosis Hygrothermal environment

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Dietary Green tea Extract and Antioxidants Improve Insulin Secretory Functions of Pancreatic β-Cells in Mild and Severe Experimental Rodent Model of Chronic Pancreatitis

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Open Journal of Endocrine and Metabolic Diseases 2024年第2期14卷 53-72页

作者： Galande Sheethal Ranjeet K. tokala Pavan Pondugala Krishna Vemula Vijayalakshmi Venkatesan Pothani Suresh Surya Satyanarayana Singh Guduru Venkat rao Duvvur Nageshwar Reddy Mitnala Sasikala Basic Science and translational Research Division Asian Healthcare Foundation AIG Hospitals Hyderabad India Division of Cell and Molecular Biology National institute of Nutrition Hyderabad India National Animal Resource Facility for Biomedical Research Hyderabad India Department of Biochemistry Osmania University Hyderabad India Department of Surgical Gastroenterology Asian Institute of Gastroenterology Hyderabad India Department of Gastroenterology Asian Institute of Gastroenterology Hyderabad India

Chronic pancreatitis (CP) is a progressive inflammatory disorder of the pancreas. It is predominantly idiopathic (with an unknown cause) in India and mostly due to alcohol in the West. Diabetes that occur secondary to chronic pancreatitis (t3c Diabetes) is often brittle, and is difficult to attain normoglycemia with conventional treatment requiring multiple doses of insulin. Mild and severe model of CP was induced in mice by repeated intraperitoneal injections of cerulein and L-arginine respectively with an intent to study islet dysfunction and develop therapeutic strategy in animal models of CP. Dietary intervention of epigallocatechin-3-gallate (EGCG) was tested in both the models of CP for its beneficial effects on insulin secretory functions. Pancreata collected upon euthanasia were used to study alterations in the morphology of pancreatic parenchyma and inflammation by staining with H&E and fibrotic changes by Masson’s trichrome and picrosirius staining. Insulin secretory functions of islets were evaluated to test the efficacy of the dietary intervention on β-cell functions. Intraperitoneal glucose tolerance test was performed to monitor the glucose homeostasis before and after the dietary intervention. Both the models resulted in CP with dispersed acini, inflammation and fibrosis. the loss of acini and extent of fibrosis was more in L-arginine model. 2-fold improvement in glucose-stimulated insulin secretory functions of islets was observed with 0.5% EGCG dietary intervention in cerulein model of CP and 1.6-fold in L-arginine model of CP. A further improvement in insulin secretion by 3.2-fold was observed with additional dietary supplements like N-acetyl cysteine, curcumin in combination with EGCG. Our results thus demonstrate and highlight the therapeutic potential of dietary green tea (EGCG) supplementation in reversing islet dysfunction and improving glucose homeostasis in experimental chronic pancreatitis in mice.

关键词： Dietary Intervention C57BL6/J Mice Epigallocatechin-3-Gallate N-Acetyl Cysteine Curcumin Chronic Pancreatitis Islets Glucose Stimulated Insulin Secretion

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维生素E联合黄体酮注射液治疗先兆流产患者的效果

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中国民康医学 2024年第5期36卷 69-72页

作者：饶卫梅信阳一五四医院妇产科河南信阳464000

目的:分析维生素E联合黄体酮注射液治疗先兆流产患者的效果。方法:回顾性分析2021年3月至2022年3月该院收治的70例先兆流产患者的临床资料,依据治疗方法不同将其分为观察组和对照组,每组35例,对照组给予黄体酮注射液治疗,观察组给予维生... 详细信息

目的:分析维生素E联合黄体酮注射液治疗先兆流产患者的效果。方法:回顾性分析2021年3月至2022年3月该院收治的70例先兆流产患者的临床资料,依据治疗方法不同将其分为观察组和对照组,每组35例,对照组给予黄体酮注射液治疗,观察组给予维生素E联合黄体酮注射液治疗。比较两组临床疗效和保胎成功率,治疗前后子宫胎盘灌注状态及性激素、辅助性t细胞(th)1/th2细胞因子和血清学指标水平。结果:治疗后,观察组治疗总有效率和保胎成功率均高于对照组,人绒毛膜促性腺激素、孕酮、雌二醇、白细胞介素(IL)-4水平高于对照组,血流搏动指数、血流阻力指数及血清γ干扰素、IL-2水平均低于对照组,差异有统计学意义(Pth1/th2细胞因子状态,利于改善妊娠结局,效果优于单纯黄体酮注射液治疗。

关键词：先兆流产维生素E 黄体酮保胎性激素血清学

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rao Algorithms-Based Structure Optimization for Heterogeneous Wireless Sensor Networks

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Computers, Materials & Continua 2024年第1期78卷 873-897页

作者： Shereen K.Refaay Samia A.Ali Moumen t.El-Melegy Louai A.Maghrabi Hamdy H.El-Sayed Faculty of Computers and Artificial Intelligence Sohag UniversitySohag82524Egypt Faculty of Engineering Assiut UniversityAssiut711745Egypt College of Engineering University of Business and TechnologyJeddah23411Saudi Arabia

the structural optimization of wireless sensor networks is a critical issue because it impacts energy consumption and hence the network’s *** studies have been conducted for homogeneous networks,but few have been performed for heterogeneouswireless sensor *** paper utilizes rao algorithms to optimize the structure of heterogeneous wireless sensor networks according to node locations and their initial *** proposed algorithms lack algorithm-specific parameters and metaphorical *** proposed algorithms examine the search space based on the relations of the population with the best,worst,and randomly assigned *** proposed algorithms can be evaluated using any routing protocol,however,we have chosen the well-known routing protocols in the literature:Low Energy Adaptive Clustering Hierarchy(LEACH),Power-Efficient Gathering in Sensor Information Systems(PEAGSIS),Partitioned-based Energy-efficient LEACH(PE-LEACH),and the Power-Efficient Gathering in Sensor Information Systems Neural Network(PEAGSIS-NN)recent routing *** compare our optimized method with the Jaya,the Particle Swarm Optimization-based Energy Efficient Clustering(PSO-EEC)protocol,and the hybrid Harmony Search Algorithm and PSO(HSA-PSO)*** efficiencies of our proposed algorithms are evaluated by conducting experiments in terms of the network lifetime(first dead node,half dead nodes,and last dead node),energy consumption,packets to cluster head,and packets to the base *** experimental results were compared with those obtained using the Jaya optimization *** proposed algorithms exhibited the best *** proposed approach successfully prolongs the network lifetime by 71% for the PEAGSIS protocol,51% for the LEACH protocol,10% for the PE-LEACH protocol,and 73% for the PEGSIS-NN protocol;Moreover,it enhances other criteria such as energy conservation,fitness convergence,packets to cluster head,and packets to the base sta

关键词： Wireless sensor networks rao algorithms optimization LEACH PEAGSIS

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二甲双胍缓释片(Ⅳ)对比其他二甲双胍缓释片治疗2型糖尿病患者疗效与安全性的网状Meta分析

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中华糖尿病杂志 2024年第8期16卷 881-888页

作者：饶翀余洁崔丽梅肖新华清华大学附属垂杨柳医院内分泌科北京100022 中国医学科学院北京协和医院内分泌科国家卫生健康委员会内分泌重点实验室北京100730

目的基于网状Meta分析(NMA)方法,系统评价二甲双胍缓释片(Ⅳ)治疗2型糖尿病(t2DM)的相对疗效与安全性。方法检索美国国立医学图书馆数据库(PubMed)、荷兰医学文摘数据库(Embase)、循证医学数据库(the Cochrane Library)、中国期刊全文... 详细信息

目的基于网状Meta分析(NMA)方法,系统评价二甲双胍缓释片(Ⅳ)治疗2型糖尿病(t2DM)的相对疗效与安全性。方法检索美国国立医学图书馆数据库(PubMed)、荷兰医学文摘数据库(Embase)、循证医学数据库(the Cochrane Library)、中国期刊全文数据库(CNKI)、万方数据库、美国食品药品监督管理局评审报告,收集比较二甲双胍缓释片(Ⅳ)和其他二甲双胍缓释片治疗t2DM患者疗效及安全性的随机对照试验(RCt),检索时限均为建库至2023年6月30日。按照纳排标准进行文献筛选,并从文献中提取资料和评价被纳入研究的偏倚风险后,采用WinBUGS 14.0软件进行NMA。结果共纳入7项RCt,3769例患者。NMA分析结果显示,二甲双胍缓释片(Ⅳ)相比于另外3种二甲双胍缓释片及二甲双胍速释片在降低糖化血红蛋白(HbA 1c)更具优势[二甲双胍缓释片(Ⅳ)相比于二甲双胍缓释片(Ⅲ)组MD=-0.62%,95%CI-0.88%~-0.36%,P0.05)。结论二甲双胍缓释片(Ⅳ)相对于前三代二甲双胍缓释片及二甲双胍速释片对t2DM具有更好的降糖作用,WADE无明显差异,二甲双胍缓释片(Ⅳ)有较为优异的降糖疗效和安全性。

关键词：糖尿病,2型二甲双胍缓释片网状Meta分析疗效安全性

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负载姜黄素的工程化细胞膜纳米颗粒的制备及其用于小鼠乳腺癌治疗的研究

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中国病理生理杂志 2024年第7期40卷 1173-1181页

作者：廖谊芳饶浪张云娇华南理工大学医学院广东广州510006 深圳湾实验室医药健康技术与工程研究所广东深圳518132

目的:制备负载姜黄素(Cur)的工程化细胞膜仿生纳米颗粒(PD1-Cur@PLGA NPs),探讨其对小鼠乳腺癌的治疗效果及潜在的肿瘤免疫调控作用。方法:构建过表达程序性死亡受体1(PD1)的工程化小鼠乳腺癌4t1-PD1细胞,并通过流式细胞术分析PD1表达... 详细信息

目的:制备负载姜黄素(Cur)的工程化细胞膜仿生纳米颗粒(PD1-Cur@PLGA NPs),探讨其对小鼠乳腺癌的治疗效果及潜在的肿瘤免疫调控作用。方法:构建过表达程序性死亡受体1(PD1)的工程化小鼠乳腺癌4t1-PD1细胞,并通过流式细胞术分析PD1表达率。提取4t1-PD1细胞膜,通过冰浴超声将其涂覆在负载Cur的聚乳酸-羟基乙酸共聚物(PLGA)纳米颗粒(Cur@PLGA NPs)表面以制备PD1-Cur@PLGA NPs;紫外可见分光光度计检测各纳米制剂的Cur负载;动态光散射和透射电镜分析各纳米制剂的粒径和形貌。将4t1细胞分为阴性对照(PLGA NPs和PD1-NVs)组、实验组(PD1-Cur@PLGA NPs组)、平行对照(Cur@PLGA NPs)组及阳性对照(Cur)组;CCK-8法检测各组细胞活力;流式细胞术分析各组细胞凋亡水平。将4t1细胞移植瘤小鼠随机分为PBS组、PD1-NVs组及PD1-Cur@PLGA NPs组,进行体内治疗实验;治疗结束后,组织染色观察主要器官的病理变化,检测肿瘤增殖(Ki67)、凋亡(tUNEL)、CD4^(+)和CD8^(+)t细胞的浸润和活性指标。结果:(1)4t1-PD1细胞系PD1表达率高达78%;(2)PD1-Cur@PLGA NPs呈类细胞壳核结构且粒径为100~200 nm;(3)PD1-Cur@PLGA NPs提高了Cur的生物相容性,且能有效诱导4t1细胞凋亡;(4)与对照组相比,PD1-Cur@PLGA NPs显著抑制了4t1乳腺癌的进展(Pt细胞的浸润和活性增强。结论:PD1-Cur@PLGA NPs提高了Cur的生物相容性,并对小鼠乳腺癌细胞具有杀伤作用。该组合制剂在体内展现出良好的治疗效果、安全性和潜在的抗肿瘤免疫调控作用。

关键词：细胞膜生物材料药物递送姜黄素乳腺癌

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基于头峰的多步分解反应过程热失控特征参数计算方法研究

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含能材料 2024年第3期32卷 280-288页

作者：乔德乾翁仕春郭子超饶国宁南京理工大学化学与化工学院江苏南京210094

目前微通道反应器在含能材料合成领域广泛应用,极大提高了合成过程的安全性,但是仍然需要关注物料的热稳定性。绝热条件下最大反应速率到达时间(tMR_(ad))与tMR_(ad)为24 h所对应的引发温度(t_(D24))是两个表征危险化学品及含能材料热... 详细信息

目前微通道反应器在含能材料合成领域广泛应用,极大提高了合成过程的安全性,但是仍然需要关注物料的热稳定性。绝热条件下最大反应速率到达时间(tMR_(ad))与tMR_(ad)为24 h所对应的引发温度(t_(D24))是两个表征危险化学品及含能材料热分解危险性的重要特征参数,这两个参数的传统计算方法为单步N级法和数值计算法,存在分析过程费时费力的缺点。为此,根据差示扫描量热仪动态升温测试曲线,提出了基于头峰(即多峰曲线分峰后的第一个峰)的热分解失控特征参数计算方法,采用穷举法比较了该方法与模型计算法的t_(D24)偏差,进行了数值模拟验证,并基于文献实验计算了1,8-二硝基蒽醌、改性硝基胍(M-NQ)、1,5-二硝基蒽醌和3,4-二硝基呋咱基氧化呋咱(DNtF)4种物质的热失控特征参数。数值模拟结果表明,对于两步和三步连续反应,t_(D24)的最大偏差百分比分别为2.88%和6.9%,最大偏差为6.41℃;对于三步连续反应,t_(D24)最大偏差为5.39℃。结果表明,4种含能材料的t_(D24)计算偏差分别为-4.55,0.71,3.16℃和-0.84℃,与模型计算法得到的t_(D24)相比,偏差百分比的绝对值均小于2%,证实了t_(D24)计算方法的有效性,计算t_(D24)时偏差较小,计算简便,能够较为准确地获得其热分解失控特征参数。

关键词：微通道多步分解反应最大反应速率到达时间头峰热分析动力学数值模拟

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Wind energy conversion system using perturb&observe-based maximum power point approach interfaced with t-type three-level inverter connected to grid

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Clean Energy 2022年第4期6卷 534-549页

作者： Pranupa S A.t.Sriram S.Nagaraja rao M S Ramaiah University of Applied Sciences BangaloreIndia

In this paper,the performance of a permanent magnet synchronous generator(PMSG)-based wind energy conversion system(WECS)supplied to an uncontrolled rectifier-fed boost converter(BC)interfaced with a three-phase t-type three-level inverter(tLI)has been *** proposed WECS involves three converters,namely an uncontrolled rectifier that is used for conversion from AC to DC;a BC supplied by a PMSG-fed rectifier used to enhance the voltage gain;and a grid-connected three-phase t-type tLI is proposed to eliminate power-quality issues with synchronization of grid voltage and *** main goal of this research is to model and control the grid-connected t-type tLI using a d-q synchronous frame for wind energy for regulating the DC-link voltage and transferring the generated wind power from the BC to the ***,the perturb&observe(P&O)-based maximum power point(MPP)approach is recommended to keep track of the MPP for a BC that is supplied from a PMSG-based WECS under constant and variable wind *** proposed PMSG-based WECS interfaced with grid-connected t-type tLI using d-q control has been computationally modelled,simulated and validated with constant and variable speeds using MAtLAB®and Simulink®.It is confirmed that the P&O-based MPP approach ensures maximum power for varying wind speeds,and the total harmonic distortion of the t-type tLI grid current value is 3.18%,which is within IEEE-519 ***,with grid synchronization,the power factor of the t-type tLI is maintained at unity to avoid power-quality issues.

关键词： boost converter grid synchronization perturb&observe t-type three-level inverter wind turbine

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