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Observation on therapeutic efficacy of ursodeoxycholic acid in Chinese patients with primary biliary

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《医学前沿（英文）》 2013年 第7卷 第2期   页码 255-263 doi: 10.1007/s11684-012-0227-1

摘要：

The efficacy of ursodeoxycholic acid (UDCA) on long-term outcome of primary biliary cirrhosis (PBC) has been less documented in Chinese cohort. We aimed to assess the therapeutic effect of UDCA on Chinese patients with PBC. In the present study, 67 patients with PBC were treated with UDCA (13–15 mg?kg-1?day-1) and followed up for 2 years to evaluate the changes of symptoms, laboratory values and histological features. As the results indicated, fatigue and pruritus were obviously improved by UDCA, particularly in patients with mild or moderate symptoms. The alkaline phosphatase and γ-glutamyl transpetidase levels significantly declined at year 2 comparing to baseline values, with the most profound effects achieved in patients at stage 2. The levels of alanine aminotransferase and aspartate aminotransferase significantly decreased whereas serum bilirubin and immunoglobulin M levels exhibited no significant change. Histological feature was stable in patients at stages 1–2 but still progressed in patients at stages 3–4. The biochemical response of patients at stage 2 was much better than that of patients at stages 3–4. These data suggest that, when treated in earlier stage, patients in long-term administration of UDCA can gain favorable results not only on symptoms and biochemical responses but also on histology. It is also indicated that later histological stage, bad biochemical response and severe symptom may be indicators of poor prognosis for UDCA therapy.

关键词： primary biliary cirrhosis     ursodeoxycholic acid     Chinese     biochemical response     therapeutic efficacy    

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提升疗效的修饰型治疗性抗体国内外研究进展 Review

戴济民, 张雪芹, 戴竞耀, 杨向民, 陈志南

《工程（英文）》 2021年 第7卷 第11期   页码 1529-1540 doi: 10.1016/j.eng.2020.06.030

摘要：

生物治疗药物市场的繁荣反映了治疗性抗体药物用于治疗癌症、炎性疾病和难治性感染的可行性和有效性。随着抗体药物临床试验和转化研究中出现的结合效率不高、效应功能降低和不良反应频发等问题的解决，治疗性抗体的修饰在抗体药物的研发进程中得到了前所未有的蓬勃发展。为了提升抗体的结合活性、循环中的半衰期、靶细胞的有效性，并最终实现改善抗体药物的疗效，抗体可主要通过以下途径修饰：①糖基化修饰；②抗体恒定区（Fc）改造；③抗体亚类重构；④构建抗体-药物偶联物（ADC）；⑤基于单链可变区片段（scFv）的嵌合抗原受体T细胞（CAR-T）；⑥双特异性抗体（bsAb）。过去几十年来全球在修饰型治疗性抗体的领域取得了许多成就，中国作为对于生物治疗药物需求巨大并且拥有巨大研发潜力的国家在该领域亦发挥了积极作用。本文概括了修饰型治疗性抗体在当前国际研究中取得的进展，并在单独的章节中重点介绍了中国在该领域取得的成果。

关键词： 治疗性抗体     抗体修饰     疗效     抗原     抗体-药物偶联物     双特异性抗体    

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A review of the safety and efficacy of current COVID-19 vaccines

《医学前沿（英文）》 2022年 第16卷 第1期   页码 39-55 doi: 10.1007/s11684-021-0893-y

摘要： Vaccination is the most effective and feasible way to contain the coronavirus disease 2019 (COVID-19) pandemic. The rapid development of effective COVID-19 vaccines is an extraordinary achievement. This study reviewed the efficacy/effectiveness, immunogenicity, and safety profile of the 12 most progressed COVID-19 vaccines and discussed the challenges and prospects of the vaccine-based approaches in a global crisis. Overall, most of the current vaccines have shown safety and efficacy/effectiveness during actual clinical trials or in the real-world studies, indicating a development of pandemic control. However, many challenges are faced by pandemic control in terms of maximizing the effect of vaccines, such as rapid vaccine coverage, strategies to address variants with immune escape capability, and surveillance of vaccine safety in the medium- and long-terms.

关键词： COVID-19     SARS-CoV-2     vaccine     safety     efficacy     effectiveness     immunogenicity    

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Circulating microRNAs in cardiovascular diseases: from biomarkers to therapeutic targets

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《医学前沿（英文）》 2014年 第8卷 第4期   页码 404-418 doi: 10.1007/s11684-014-0379-2

摘要：

microRNAs (miRNAs) are a class of conserved, short, non-coding RNAs that have important and potent capacities to regulate gene expression at the posttranscriptional level. In the past several years, the aberrant expressions of miRNAs in the cardiovascular system have been widely reported, and the crucial roles of some special miRNAs in heart development and pathophysiology of various cardiovascular diseases have been gradually recognized. Recently, it was discovered that miRNAs are presented in peripheral circulation abundantly and stably. This has raised the possibility of using circulating miRNAs as biomarkers for diseases. Furthermore, some studies demonstrated that circulating miRNAs may serve as novel extracellular communicators of cell-cell communication. These discoveries not only reveal the functions of circulating miRNAs in cardiovascular system but also inform the development of miRNAs therapeutic strategies. In this review, we discuss the potential roles of circulating miRNAs in a variety of cardiovascular diseases from biomarkers to therapeutic targets to clearly understand the roles of circulating miRNAs in cardiovascular system.

关键词： microRNA     cardiovascular disease     biomarkers     therapeutic target    

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Brown and beige fat: the metabolic function, induction, and therapeutic potential

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《医学前沿（英文）》 2015年 第9卷 第2期   页码 162-172 doi: 10.1007/s11684-015-0382-2

摘要：

Adipose tissue is an important organ for energy homeostasis. White adipose tissue stores energy in the form of triglycerides, whereas brown adipocytes and recently identified beige adipocytes are specialized in dissipating energy by thermogenesis or contribution to dispose glucose and clear triglycerides in blood. The inverse correlation between the brown adipose tissue activity and body mass suggests its protective role against body fat accumulation. Thus, recruitment and activation of brown or beige adipose tissue become particularly appealing targets for increasing energy expenditure. Angiogenesis and sympathetic nerve signals are the fundamental determinants for brown and beige adipose tissue development, as well as for their metabolic functions. Secretary factors including BMPs can induce the development, the activation of brown or beige adipose tissue, which seem to be promising for therapeutic development.

关键词： brown adipocyte     beige adipocyte     metabolism     obesity    

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基于整合临床和动物实验的小分子筛选平台揭示经典方剂茵陈蒿汤治疗黄疸证显效状态下的活性化合物及潜在作用靶点 Article

熊辉, 张爱华, 郭雅静, 周小航, 孙晖, 杨乐, 方衡, 闫广利, 王喜军

《工程（英文）》 2021年 第7卷 第9期   页码 1293-1305 doi: 10.1016/j.eng.2020.12.016

摘要：

中药方剂化学组成高度复杂，其药理作用具有多成分、多靶点的特点，使得阐明其生物活性化合物极具挑战性。茵陈蒿汤被广泛用于治疗黄疸相关疾病。尽管近年来茵陈蒿汤的药效及活性成分被不断证实，但仍然缺乏对其效应成分、效应机制和功能靶点的深入系统分析，尤其是临床研究方面。本研究建立了一个整合临床和动物实验平台用于发现茵陈蒿汤的活性化合物和潜在靶点。首先采用基于超高效液相色谱-四极杆飞行时间质谱（UPLC-Q-ToF-MS）技术的代谢组学方法结合中药血清药物化学方法揭示茵陈蒿汤的血清代谢谱和化学成分谱。此外，通过网络药理学和智能途径分析平台构建化合物-靶标-通路关联网络。最终发现茵陈蒿汤中8 个活性小分子与5 个核心靶点极度相关，并通过酶联免疫吸附测定实验进行生物学验证。结果表明茵陈蒿汤通过靶向胆固醇7α-羟化酶（CYP7A1）、多药耐药相关蛋白2（ABCC2）、多药耐药相关蛋白3（ABCC3）、尿苷二磷酸葡萄糖醛酸基转移酶1A1（UGT1A1）和法尼醇X受体（FXR）来调节包括初级胆汁酸生物合成、卟啉和叶绿素代谢以及胆汁分泌在内的代谢通路，从而发挥利胆退黄的作用。该整合策略可以成功地用于中药方剂活性小分子及其作用靶点的发现。

关键词： 有效性     活性化合物     小分子     靶点     中药     代谢组学    

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Molecular mechanisms and therapeutic strategies of vulnerable atherosclerotic plaques

Wen-Qiang CHEN MD, Yun ZHANG MD, PhD, FACC,

《医学前沿（英文）》 2010年 第4卷 第1期   页码 36-42 doi: 10.1007/s11684-010-0020-y

摘要： Vulnerable atherosclerotic plaque rupture leading to thrombosis is the major cause of acute coronary syndrome (ACS). Studies on the pathophysiologic mechanism of both ACS and plaque stabilizing treatment are driving the development of animal models of vulnerable plaque. In our laboratory, we established animal models of plaque rupture and thrombosis in rabbits and mice that are similar to human plaque rupture. Potential mechanisms involved in plaque vulnerability were studied from the inflammation-immunity, proliferation-apoptosis, oxidative stress and biomechanics aspects. Imaging markers and biomarkers were used to detect vulnerable plaques, including high frequency duplex ultrasound, intravascular ultrasound (IVUS), intravascular ultrasound elastography, magnetic resonance imaging (MRI) and inflammatory markers. Effective gene and drug strategies to treat vulnerable plaques were explored.

关键词： vulnerable plaque     animal models     mechani-sm     detection     treatment    

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Heterogeneous influence of individuals’ behavior on mask efficacy in gathering environments

《工程管理前沿（英文）》   页码 550-562 doi: 10.1007/s42524-022-0193-5

摘要： Wearing masks is an easy way to operate and popular measure for preventing epidemics. Although masks can slow down the spread of viruses, their efficacy in gathering environments involving heterogeneous person-to-person contacts remains unknown. Therefore, we aim to investigate the epidemic prevention effect of masks in different real-life gathering environments. This study uses four real interpersonal contact datasets to construct four empirical networks to represent four gathering environments. The transmission of COVID-19 is simulated using the Monte Carlo simulation method. The heterogeneity of individuals can cause mask efficacy in a specific gathering environment to be different from the baseline efficacy in general society. Furthermore, the heterogeneity of gathering environments causes the epidemic prevention effect of masks to differ. Wearing masks can greatly reduce the probability of clustered epidemics and the infection scale in primary schools, high schools, and hospitals. However, the use of masks alone in primary schools and hospitals cannot control outbreaks. In high schools with social distancing between classes and in workplaces where the interpersonal contact is relatively sparse, masks can meet the need for prevention. Given the heterogeneity of individual behavior, if individuals who are more active in terms of interpersonal contact are prioritized for mask-wearing, the epidemic prevention effect of masks can be improved. Finally, asymptomatic infection has varying effects on the prevention effect of masks in different environments. The effect can be weakened or eliminated by increasing the usage rate of masks in high schools and workplaces. However, the effect on primary schools and hospitals cannot be weakened. This study contributes to the accurate evaluation of mask efficacy in various gathering environments to provide scientific guidance for epidemic prevention.

关键词： COVID-19     masks     behavioral heterogeneity     asymptomatic infection    

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Advances in COVID-19: the virus, the pathogenesis, and evidence-based control and therapeutic strategies

Guangbiao Zhou, Saijuan Chen, Zhu Chen

《医学前沿（英文）》 2020年 第14卷 第2期   页码 117-125 doi: 10.1007/s11684-020-0773-x

摘要： Since the outbreak of the COVID-19 pandemic in early December 2019, 81 174 confirmed cases and 3242 deaths have been reported in China as of March 19, 2020. The Chinese people and government have contributed huge efforts to combat this disease, resulting in significant improvement of the situation, with 58 new cases (34 were imported cases) and 11 new deaths reported on March 19, 2020. However, as of March 19, 2020, the COVID-19 pandemic continues to develop in 167 countries/territories outside of China, and 128 665 confirmed cases and 5536 deaths have been reported, with 16 498 new cases and 817 new deaths occurring in last 24 hours. Therefore, the world should work together to fight against this pandemic. Here, we review the recent advances in COVID-19, including the insights in the virus, the responses of the host cells, the cytokine release syndrome, and the therapeutic approaches to inhibit the virus and alleviate the cytokine storm. By sharing knowledge and deepening our understanding of the virus and the disease pathogenesis, we believe that the community can efficiently develop effective vaccines and drugs, and the mankind will eventually win this battle against this pandemic.

关键词： COVID-19     SARS-CoV-2     pathogenesis     evidence-based medicine     control and therapeutic strategies    

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Retrospective study of the efficacy and complication of thoracoabdominal incision for nephrectomy: a

Minggen YANG, Xiaokun ZHAO

《医学前沿（英文）》 2009年 第3卷 第2期   页码 191-196 doi: 10.1007/s11684-009-0026-5

摘要： This retrospective study was performed to compare the outcome of thoracoabdominal incision flank incision for radical nephrectomy in the patients with large renal tumors. A questionnaire assessing postoperative pain, administration of pain medications and the return to activities and work was sent to the patients who undergoing radical nephrectomy through the 11th rib (group 1: underwent flank incision, including 96 patients) or the 9th to 10th rib (group 2: undergoing thoracoabdominal incision, including 98 patients) from 2003 to 2007 in our hospital. A case retrospective analysis assessing operation time, perioperative hemorrhage volume, size of tumor, success in the treatment of tumor thrombus in renal vein or vena cava, time length of presence of drainage tube, postoperative analgesia usage and length of stay was conducted in patients whose questionnaires were returned. A total of 56 patients (58%) in group 1 and 60 (61%) in group 2 responded to the questionnaire. Time lengths of operation and presence of abdominal drainage tube were shorter in group 2 than those in group 1. Perioperative hemorrhage volume in group 2 was obviously less than that in group 1. The mean size of tumors in group 1 was significantly smaller than that in group 2 ( < 0.0005). The success rate of treating thrombus in renal vein or vena cava in group 2 was significantly higher than that in group 1 ( <0.05). Lengths of off-bed time and stay were the same in both groups. There were no differences between groups in terms of pain severity on postoperative day 1, on day of discharge and 1 month postoperatively ( >0.05). There were no significant differences between groups in the time following surgery when pain completely disappeared, when pain medications were discontinued, and when the patient returned to daily activities and work ( >0.05). The thoracoabdominal incision provides excellent exposure and allows for early vascular control. Efficacy and complication was comparable for thoracoabdominal and flank incisions in terms of incisional pain, analgesic requirements after discharge and return to normal activities.

关键词： surgery     renal tumors     nephrectomy    

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Resistance to receptor tyrosine kinase inhibition in cancer: molecular mechanisms and therapeutic strategies

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《医学前沿（英文）》 2015年 第9卷 第2期   页码 134-138 doi: 10.1007/s11684-015-0396-9

摘要：

Drug resistance is a major factor that limits the efficacy of targeted cancer therapies. In this review, we discuss the main known mechanisms of resistance to receptor tyrosine kinase inhibitors, which are the most prevalent class of targeted therapeutic agent in current clinical use. Here we focus on bypass track resistance, which involves the activation of alternate signaling molecules by tumor cells to bypass inhibition and maintain signaling output, and consider the problems of signaling pathway redundancy and how the activation of different receptor tyrosine kinases translates into intracellular signal transduction in different cancer types. This information is presented in the context of research strategies for the discovery of new targets for pharmacological intervention, with the goal of overcoming resistance in order to improve patient outcomes.

关键词： targeted therapy     drug resistance     receptor tyrosine kinases     cancer    

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Triterpenoid inducers of Nrf2 signaling as potential therapeutic agents in sickle cell disease: a review

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《医学前沿（英文）》 2015年 第9卷 第1期   页码 46-56 doi: 10.1007/s11684-015-0375-1

摘要：

Sickle cell disease (SCD) is an inherited disorder of hemoglobin in which the abnormal hemoglobin S polymerizes when deoxygenated. This polymerization of hemoglobin S not only results in hemolysis and vaso-occlusion but also precipitates inflammation, oxidative stress and chronic organ dysfunction. Oxidative stress is increasingly recognized as an important intermediate in these pathophysiological processes and is therefore an important target for therapeutic intervention. The transcription factor nuclear erythroid derived- 2 related factor 2 (Nrf2) controls the expression of anti-oxidant enzymes and is emerging as a protein whose function can be exploited with therapeutic intent. This review article is focused on triterpenoids that activate Nrf2, and their potential for reducing oxidative stress in SCD as an approach to prevent organ dysfunction associated with this disease. A brief overview of oxidative stress in the clinical context of SCD is accompanied by a discussion of several pathophysiological mechanisms contributing to oxidative stress. Finally, these mechanisms are then related to current management strategies in SCD that are either utilized currently or under evaluation. The article concludes with a perspective on the potential of the various therapeutic interventions to reduce oxidative stress and morbidity associated with SCD.

关键词： oxidative stress     Nrf2     triterpenoids     sickle cell disease     vaso-occlusion     CDDO-Me    

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Improving the prognosis of pancreatic cancer: insights from epidemiology, genomic alterations, and therapeutic

《医学前沿（英文）》 doi: 10.1007/s11684-023-1050-6

摘要： Pancreatic cancer, notorious for its late diagnosis and aggressive progression, poses a substantial challenge owing to scarce treatment alternatives. This review endeavors to furnish a holistic insight into pancreatic cancer, encompassing its epidemiology, genomic characterization, risk factors, diagnosis, therapeutic strategies, and treatment resistance mechanisms. We delve into identifying risk factors, including genetic predisposition and environmental exposures, and explore recent research advancements in precursor lesions and molecular subtypes of pancreatic cancer. Additionally, we highlight the development and application of multi-omics approaches in pancreatic cancer research and discuss the latest combinations of pancreatic cancer biomarkers and their efficacy. We also dissect the primary mechanisms underlying treatment resistance in this malignancy, illustrating the latest therapeutic options and advancements in the field. Conclusively, we accentuate the urgent demand for more extensive research to enhance the prognosis for pancreatic cancer patients.

关键词： pancreatic cancer     cancer screening     single cell     molecular alterations     precancerous lesion     therapy resistance    

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Base editors: development and applications in biomedicine

《医学前沿（英文）》 2023年 第17卷 第3期   页码 359-387 doi: 10.1007/s11684-023-1013-y

摘要： Base editor (BE) is a gene-editing tool developed by combining the CRISPR/Cas system with an individual deaminase, enabling precise single-base substitution in DNA or RNA without generating a DNA double-strand break (DSB) or requiring donor DNA templates in living cells. Base editors offer more precise and secure genome-editing effects than other conventional artificial nuclease systems, such as CRISPR/Cas9, as the DSB induced by Cas9 will cause severe damage to the genome. Thus, base editors have important applications in the field of biomedicine, including gene function investigation, directed protein evolution, genetic lineage tracing, disease modeling, and gene therapy. Since the development of the two main base editors, cytosine base editors (CBEs) and adenine base editors (ABEs), scientists have developed more than 100 optimized base editors with improved editing efficiency, precision, specificity, targeting scope, and capacity to be delivered in vivo, greatly enhancing their application potential in biomedicine. Here, we review the recent development of base editors, summarize their applications in the biomedical field, and discuss future perspectives and challenges for therapeutic applications.

关键词： base editing     CBE     ABE     ADAR     DdCBE     disease model     therapeutic application    

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AML1-ETO driven acute leukemia: insights into pathogenesis and potential therapeutic approaches

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《医学前沿（英文）》 2012年 第6卷 第3期   页码 248-262 doi: 10.1007/s11684-012-0206-6

摘要：

The AML1-ETO fusion transcription factor is generated by the t(8;21) translocation, which is present in approximately 4%–12% of adult and 12%–30% of pediatric acute myeloid leukemia (AML) patients. Both human and mouse models of AML have demonstrated that AML1-ETO is insufficient for leukemogenesis in the absence of secondary events. In this review, we discuss the pathogenetic insights that have been gained from identifying the various events that can cooperate with AML1-ETO to induce AML in vivo. We also discuss potential therapeutic strategies for t(8;21) positive AML that involve targeting the fusion protein itself, the proteins that bind to it, or the genes that it regulates. Recently published studies suggest that a targeted therapy for t(8;21) positive AML is feasible and may be coming sometime soon.

关键词： AML1-ETO     mouse model     leukemia     t(8     21)     pathway hits     mutation     hematopoiesis     Kasumi-1     CD34+    

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标题 作者 时间 类型 操作

Observation on therapeutic efficacy of ursodeoxycholic acid in Chinese patients with primary biliary

null

期刊论文

提升疗效的修饰型治疗性抗体国内外研究进展

戴济民, 张雪芹, 戴竞耀, 杨向民, 陈志南

期刊论文

A review of the safety and efficacy of current COVID-19 vaccines

期刊论文

Circulating microRNAs in cardiovascular diseases: from biomarkers to therapeutic targets

null

期刊论文

Brown and beige fat: the metabolic function, induction, and therapeutic potential

null

期刊论文

基于整合临床和动物实验的小分子筛选平台揭示经典方剂茵陈蒿汤治疗黄疸证显效状态下的活性化合物及潜在作用靶点

熊辉, 张爱华, 郭雅静, 周小航, 孙晖, 杨乐, 方衡, 闫广利, 王喜军

期刊论文

Molecular mechanisms and therapeutic strategies of vulnerable atherosclerotic plaques

Wen-Qiang CHEN MD, Yun ZHANG MD, PhD, FACC,

期刊论文

Heterogeneous influence of individuals’ behavior on mask efficacy in gathering environments

期刊论文

Advances in COVID-19: the virus, the pathogenesis, and evidence-based control and therapeutic strategies

Guangbiao Zhou, Saijuan Chen, Zhu Chen

期刊论文

Retrospective study of the efficacy and complication of thoracoabdominal incision for nephrectomy: a

Minggen YANG, Xiaokun ZHAO

期刊论文

Resistance to receptor tyrosine kinase inhibition in cancer: molecular mechanisms and therapeutic strategies

null

期刊论文

Triterpenoid inducers of Nrf2 signaling as potential therapeutic agents in sickle cell disease: a review

null

期刊论文

Improving the prognosis of pancreatic cancer: insights from epidemiology, genomic alterations, and therapeutic

期刊论文

Base editors: development and applications in biomedicine

期刊论文

AML1-ETO driven acute leukemia: insights into pathogenesis and potential therapeutic approaches

null

期刊论文