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Efficacy and safety of benralizumab in patients with eosinophilic asthma: a meta-analysis of randomized placebo-controlled trials

null

《医学前沿（英文）》 2018年 第12卷 第3期   页码 340-349 doi: 10.1007/s11684-017-0565-0

摘要：

Benralizumab is a monoclonal antibody that targets interleukin-5 receptor α to deplete blood eosinophils and improve the clinical outcomes of allergic asthma. We conducted a meta-analysis to evaluate the safety and efficacy of different doses of benralizumab in patients with eosinophilic asthma. All randomized controlled trials involving benralizumab treatment for patients with eosinophilic asthma, which were searched in PubMed, Embase, and the Cochrane Library published until January 2017, as well as the rate of asthmatic exacerbation, pulmonary functionality, asthma control, quality of life scores, and adverse events were included. Randomized-effect models were used in the meta-analysis to calculate the pooled mean difference, relative risks, and 95% confidence intervals. Five studies involving 1951 patients were identified. Compared with the placebo, benralizumab treatment demonstrated significant improvements in the forced expiratory volume in 1?s (FEV1), Asthma Quality of Life Questionnaire scores, decreased asthmatic exacerbation and Asthma Control Questionnaire-6 (ACQ-6) scores. Benralizumab treatment was also not associated with increased adverse events. These findings indicated that benralizumab can be safely used to improve FEV1, enhance patient symptom control and quality of life, and reduce the risk of exacerbations and ACQ-6 scores in patients with eosinophilic asthma. Furthermore, our meta-analysis showed that benralizumab with 30 mg (every eight weeks) dosage can improve the health-related quality of life and appear to be more effective than 30 mg (every four weeks) dosage. Overall, data indicated that the optimal dosing regimen for benralizumab was possibly 30 mg (every eight weeks).

关键词： benralizumab     anti-interleukin-5     monoclonal antibody     eosinophilic asthma     meta-analysis    

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murine pancreatic carcinoma by β-elemene combined with dendritic cells modified with genes encoding interleukin

TAN Guang, WANG Zhongyu, CHE Luanqing, YIN Shuo

《医学前沿（英文）》 2007年 第1卷 第1期   页码 41-45 doi: 10.1007/s11684-007-0008-4

摘要： The dendritic cell vaccine is a treatment vaccine with potent clinical applications. Functional cytokines can enhance dendritic cell anti-tumor immune responses. This experiment was conducted to study the effects of bone marrow-deriv

关键词： Functional     experiment     anti-tumor     dendritic     clinical    

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Keratin 5-Cre-driven deletion of

Jun Yang, Lianqing Wang, Yingzhi Huang, Keqiang Liu, Chaoxia Lu, Nuo Si, Rongrong Wang, Yaping Liu, Xue Zhang

《医学前沿（英文）》 2020年 第14卷 第3期   页码 305-317 doi: 10.1007/s11684-019-0722-8

摘要： Familial acne inversa (AI) is an autoinflammatory disorder that affects hair follicles and is caused by loss-of-function mutations in -secretase component genes. We and other researchers showed that ( ) is the most frequently mutated gene in familial AI. In this study, we generated a keratin 5-Cre-driven epidermis-specific conditional knockout mutant in mice. We determined that this mutant recapitulated the major phenotypes of AI, including hyperkeratosis of hair follicles and inflammation. In mice, the IL-36a expression level markedly increased starting from postnatal day 0 (P0), and this increase occurred much earlier than those of TNF- , IL-23A, IL-1 and TLR4. RNA-Seq analysis indicated that Sprr2d, a member of the small proline-rich protein 2 family, in the skin tissues of the mice was also upregulated on P0. Quantitative reverse-transcription polymerase chain reaction showed that other genes had a similar expression pattern. Our findings suggested that IL-36a might be a key inflammatory cytokine in the pathophysiology of AI and involved in the malfunction of the skin barrier in the pathogenesis of AI.

关键词： acne inversa mouse model     interleukin 1 family     member 6     small proline rich protein 2D     key inflammatory cytokine    

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Beneficial metabolic activities of inflammatory cytokine interleukin 15 in obesity and type 2 diabetes

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《医学前沿（英文）》 2015年 第9卷 第2期   页码 139-145 doi: 10.1007/s11684-015-0377-z

摘要：

In obesity, chronic inflammation is believed to induce insulin resistance and impairs adipose tissue function. Although this view is supported by a large body of literature, it has been challenged by growing evidence that pro-inflammatory cytokines may favor insulin sensitivity through induction of energy expenditure. In this review article, interleukin 15 (IL-15) is used as a new example to explain the beneficial effects of the pro-inflammatory cytokines. IL-15 is secreted by multiple types of cells including macrophages, neutrophils and skeletal muscle cells. IL-15 expression is induced in immune cells by endotoxin and in muscle cells by physical exercise. Its transcription is induced by transcription factor NF-κB. IL-15 binds to its receptor that contains three different subunits (α, β and γ) to activate JAK/STAT, PI3K/Akt, IKK/NF-κB and JNK/AP1 pathways in cells. In the regulation of metabolism, IL-15 reduces weight gain without inhibiting food intake in rodents. IL-15 suppresses lipogenesis, stimulates brown fat function, improves insulin sensitivity through weight loss and energy expenditure. In human, circulating IL-15 is negatively associated with body weight. In the immune system, IL-15 stimulates proliferation and differentiation of T cells, NK cells, monocytes and neutrophils. In the anti-obesity effects of IL-15, T cells and NK cells are not required, but leptin receptor is required. In summary, evidence from human and rodents supports that the pro-inflammatory cytokine IL-15 may enhance energy expenditure to protect the body from obesity and type 2 diabetes. The mechanism of IL-15 action remains to be fully uncovered in the regulation of energy expenditure.

关键词： inflammation     obesity     cytokine     energy expenditure     insulin resistance    

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Research on the control systems of a precision linear motor drive device

YAN Han, WANG Xian-kui, DUAN Guang-hong

《机械工程前沿（英文）》 2006年 第1卷 第3期   页码 260-264 doi: 10.1007/s11465-006-0036-9

摘要： The model of a precision linear motor drive device (PLMDD) and its control requirements are analyzed. In order to enhance the tracking and anti-disturbance performance of the system, its third-order model is established, and disturbance-observer based input revising feedforward error compensation robust control algorithm, combined with integral-separated proportional integral derivative (PID) control algorithm is proposed. This includes feedback control algorithm and feedforward control algorithm. The feedback controller improves system tracking performance and suppresses load and mechanical disturbance while the feedforward controller compensates phase hysteresis introduced by feedback control. Theoretical analyses, simulations and experiments show that this control method increases the tracking precision of PLMDD from ±5 μm to ±2 μm and dramatically improves its anti-disturbance ability.

关键词： feedforward     tracking     ±5     anti-disturbance performance     algorithm    

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QUANTITATIVE STUDY ON ANTI-PEST ACTIVITY OF NATURAL PRODUCTS BASED ON VISUALIZATION FRAMEWORK OF KNOWLEDGE

《农业科学与工程前沿（英文）》 2023年 第10卷 第2期   页码 306-332 doi: 10.15302/J-FASE-2023488

摘要：

● Using visual analysis to predict the trend of natural product pest resistance.

关键词： anti-pest activity     crop protection     insect pest     natural product     visual analysis    

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Dihydroartemisinin increased the abundance of by YAP1 depression that sensitizes hepatocellular carcinoma to anti-PD

《医学前沿（英文）》 2023年 第17卷 第4期   页码 729-746 doi: 10.1007/s11684-022-0978-2

摘要： The effect of anti-programmed cell death 1 (anti-PD-1) immunotherapy is limited in patients with hepatocellular carcinoma (HCC). Yes-associated protein 1 (YAP1) expression increased in liver tumor cells in early HCC, and Akkermansia muciniphila abundance decreased in the colon. The response to anti-PD-1 treatment is associated with A. muciniphila abundance in many tumors. However, the interaction between A. muciniphila abundance and YAP1 expression remains unclear in HCC. Here, anti-PD-1 treatment decreased A. muciniphila abundance in the colon, but increased YAP1 expression in the tumor cells by mice with liver tumors in situ. Mechanistically, hepatocyte-specific Yap1 knockout (Yap1LKO) maintained bile acid homeostasis in the liver, resulting in an increased abundance of A. muciniphila in the colon. Yap1 knockout enhanced anti-PD-1 efficacy. Therefore, YAP1 inhibition is a potential target for increasing A. muciniphila abundance to promote anti-PD-1 efficacy in liver tumors. Dihydroartemisinin (DHA), acting as YAP1 inhibitor, increased A. muciniphila abundance to sensitize anti-PD-1 therapy. A. muciniphila by gavage increased the number and activation of CD8+ T cells in liver tumor niches during DHA treatment or combination with anti-PD-1. Our findings suggested that the combination anti-PD-1 with DHA is an effective strategy for liver tumor treatment.

关键词： hepatocellular carcinoma     YAP1     Akkermansia muciniphila     anti-PD-1     dihydroartemisinin     bile acid    

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Association of miRNA-122-binding site polymorphism at the interleukin-1 α gene and its interaction with

null

《医学前沿（英文）》 2014年 第8卷 第2期   页码 217-226 doi: 10.1007/s11684-014-0326-2

摘要：

This study was designed to investigate the contribution of miRNA-122-binding site polymorphism at the IL-1A gene and its multiplicative interactions with hepatitis B virus (HBV) mutations in the risk of hepatocellular carcinoma (HCC). A total of 1021 healthy controls, 302 HBV surface antigen (HBsAg) seroclearance subjects, and 2011 HBsAg-positive subjects (including 1021 HCC patients) were enrolled in this study. Quantitative PCR was used to genotype rs3783553. HBV mutations were determined by direct sequencing. Multivariate logistic regression analyses were performed to test the associations of rs3783553, mutations, and their interactions with the risk of HCC. No significant association was found between rs3783553 and the risk of HCC among healthy controls, HBsAg seroclearance subjects, HBsAg-positive subjects without HCC, and all controls. Additionally, rs3783553 was not significantly associated with chronic HBV infection, liver cirrhosis, HBV e antigen seroconversion, abnormal alanine aminotransferase, and high viral load (>104 copies/ml). However, the TTCA insertion allele of rs3783553 was significantly associated with an increased frequency of HBV C7A mutation compared with homozygous TTCA deletion carriers [(del/ins+ ins/ins) vs. del/del, adjusted odds ratio (OR)=1.48, 95% confidence interval (CI)=1.09-2.02, P=0.013]. Multiplicative interaction of rs3783553 with HBV preS deletion significantly reduced the risk of HCC in males, with an adjusted OR of 0.64 (95% CI=0.42-0.98; P=0.041) after age and HBV genotype were adjusted. Although rs3783553 did not significantly affect genetic susceptibility to HBV-related HCC, its variant allele may predispose the host to selecting HBV C7A mutation during evolution and significantly reduce the risk of HCC caused by HBV preS deletion. This study provides an insight into the complex host-virus interaction in HBV-induced hepatocarcinogenesis and is helpful in determining HBsAg-positive subjects who are likely to develop HCC.

关键词： hepatocellular carcinoma (HCC)     interaction     miRNA-122-binding site     IL-1A     rs3783553     hepatitis B virus (HBV) mutations    

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Cytokine storm and translating IL-6 biology into effective treatments for COVID-19

《医学前沿（英文）》 doi: 10.1007/s11684-023-1044-4

摘要： As of May 3, 2023, the coronavirus disease 2019 (COVID-19) pandemic has resulted in more than 760 million confirmed cases and over 6.9 million deaths. Several patients have developed pneumonia, which can deteriorate into acute respiratory distress syndrome. The primary etiology may be attributed to cytokine storm, which is triggered by the excessive release of proinflammatory cytokines and subsequently leads to immune dysregulation. Considering that high levels of interleukin-6 (IL-6) have been detected in several highly pathogenic coronavirus-infected diseases, such as severe acute respiratory syndrome in 2002, the Middle East respiratory syndrome in 2012, and COVID-19, the IL-6 pathway has emerged as a key in the pathogenesis of this hyperinflammatory state. Thus, we review the history of cytokine storm and the process of targeting IL-6 signaling to elucidate the pivotal role played by tocilizumab in combating COVID-19.

关键词： SARS-CoV-2     COVID-19     cytokine storm     interleukin-6     tocilizumab    

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A modular cable-driven humanoid arm with anti-parallelogram mechanisms and Bowden cables

《机械工程前沿（英文）》 2023年 第18卷 第1期 doi: 10.1007/s11465-022-0722-2

摘要： This paper proposes a novel modular cable-driven humanoid arm with anti-parallelogram mechanisms (APMs) and Bowden cables. The lightweight arm realizes the advantage of joint independence and the rational layout of the driving units on the base. First, this paper analyzes the kinematic performance of the APM and uses the rolling motion between two ellipses to approximate a pure-circular-rolling motion. Then, a novel type of one-degree-of-freedom (1-DOF) elbow joint is proposed based on this principle, which is also applied to design the 3-DOF wrist and shoulder joints. Next, Bowden cables are used to connect the joints and their driving units to obtain a modular cable-driven arm with excellent joint independence. After that, both the forward and inverse kinematics of the entire arm are analyzed. Last, a humanoid arm prototype was developed, and the assembly velocity, joint motion performance, joint stiffness, load carrying, typical humanoid arm movements, and repeatability were tested to verify the arm performance.

关键词： modular robotic arm     anti-parallelogram mechanism     Bowden cable     humanoid arm     lightweight joint design    

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Anti-biofouling strategies for implantable biosensors of continuous glucose monitoring systems

《化学科学与工程前沿（英文）》 2023年 第17卷 第12期   页码 1866-1878 doi: 10.1007/s11705-023-2340-x

摘要： Continuous glucose monitoring (CGM) systems play an increasingly vital role in the glycemic control of patients with diabetes mellitus. However, the immune responses triggered by the implantation of poorly biocompatible sensors have a significant impact on the accuracy and lifetime of CGM systems. In this review, research efforts over the past few years to mitigate the immune responses by enhancing the anti-biofouling ability of sensors are summarized. This review divided these works into active immune engaging strategy and passive immune escape strategy based on their respective mechanisms. In each strategy, the various biocompatible layers on the biosensor surface, such as drug-releasing membranes, hydrogels, hydrophilic membranes, anti-biofouling membranes based on zwitterionic polymers, and bio-mimicking membranes, are described in detail. This review, therefore, provides researchers working on implantable biosensors for CGM systems with vital information, which is likely to aid in the research and development of novel CGM systems with profound anti-biofouling properties.

关键词： implantable glucose biosensor     anti-biofouling     continuous glucose monitoring     immune responses    

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Lignin-derived dual-function red light carbon dots for hypochlorite detection and anti-counterfeiting

《化学科学与工程前沿（英文）》 2023年 第17卷 第7期   页码 966-975 doi: 10.1007/s11705-022-2244-1

摘要： The efficient utilization of natural lignin, which is the main by-product of the cellulose industry, is crucial for enhancing its economic value, alleviating the environmental burden, and improving ecological security. By taking advantage of the large sp2 hybrid domain of lignin and introducing amino functional groups, new lignin-derived carbon dots (SPN-CDs) with red fluorescence were successfully synthesized. Compared with green and blue fluorescent materials, red SPN-CDs have desirable anti-interference properties of short-wave background and exhibit superior luminescence stability. The SPN-CDs obtained exhibited sensitive and distinctive visible color with fluorescence-dual responses toward hypochlorite. Considering this feature, a portable, low-cost, and sensitive fluorescence sensing paper with a low limit of detection of 0.249 μmol∙L–1 was fabricated using the SPN-CDs for hypochlorite detection. Furthermore, a new type of visible-light and fluorescence dual-channel information encryption platform was constructed. Low-concentration hypochlorite can be employed as an accessible and efficient information encryption/decryption stimulus, as well as an information “eraser”, facilitating a safe and diversified transmission and convenient decryption of information. This work opens new avenues for high-value-added applications of lignin-based fluorescent materials.

关键词： alkali lignin     red light carbon dots     hypochlorite     encryption and anti-counterfeiting    

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Modulatory effect on dyslipidemia and anti-atherosclerotic function of in newly diagnosed type 2 diabetes

SUN Mingxiao, WANG Yao, CHI Jiamin

《医学前沿（英文）》 2008年 第2卷 第2期   页码 174-177 doi: 10.1007/s11684-008-0032-z

摘要： The modulatory effect of on dyslipidemia and the preventive effect on atherosclerosis in newly diagnosed type 2 diabetic patients were studied. A prospective clinical trial was conducted to test the effectiveness of in selected 201 newly diagnosed type 2 diabetic patients. All patients were randomly divided into two groups: 108 with therapy and 93 without therapy. The mean follow-up period was 22 months. The blood glucose and blood pressure of all patients were under control. Serum levels of total cholesterol (TC), triglyceride (TG), and low density lipoprotein cholesterol (LDL-C) were significantly lowered and their decreased percentages were significantly higher in therapy group ( < 0.05). The number of patients with arteria iliaca intima thickening was significantly lower in group of therapy ( = 0.024). With stepwise multivariate logistic regression analysis, the decreased percentage of TG was significantly and independently related with the decreased number of patients with arteria iliaca intima thickening ( = 0.005). The study demonstrates that therapy is effective on modulating dyslipidemia in newly diagnosed type 2 diabetes patients, and may be related with the improvement of early atherosclerosis.
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Preparation of reverse osmosis membrane with high permselectivity and anti-biofouling properties for

《环境科学与工程前沿（英文）》 2022年 第16卷 第7期 doi: 10.1007/s11783-021-1497-0

摘要：

• Nanoparticle incorporation and anti-biofouling grafting were integrated.

关键词： Anti-biofouling grafting     Nanoparticle incorporation     Sterilization rates     Water flux     Water flux recovery    

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Small-molecule anti-COVID-19 drugs and a focus on China’s homegrown mindeudesivir (VV116)

《医学前沿（英文）》 doi: 10.1007/s11684-023-1037-3

摘要： The coronavirus disease 2019 (COVID-19) pandemic has stimulated tremendous efforts to develop therapeutic agents that target severe acute respiratory syndrome coronavirus 2 to control viral infection. So far, a few small-molecule antiviral drugs, including nirmatrelvir–ritonavir (Paxlovid), remdesivir, and molnupiravir have been marketed for the treatment of COVID-19. Nirmatrelvir–ritonavir has been recommended by the World Health Organization as an early treatment for outpatients with mild-to-moderate COVID-19. However, the existing treatment options have limitations, and effective treatment strategies that are cost-effective and convenient for tackling COVID-19 are still needed. To date, four domestically developed oral anti-COVID-19 drugs have been granted conditional market approval in China. These drugs include azvudine, simnotrelvir–ritonavir (Xiannuoxin), leritrelvir, and mindeudesivir (VV116). Preclinical and clinical studies have explored the efficacy and tolerability of mindeudesivir and supported its early use in mild-to-moderate COVID-19 cases at high risk for progression. In this review, we discuss the most recent findings regarding the pharmacological mechanism and therapeutic effects focusing on mindeudesivir and other small-molecule antiviral agents for COVID-19. These findings will expand our understanding and highlight the potential widespread application of China’s homegrown anti-COVID-19 drugs.

关键词： COVID-19     antiviral drugs     mindeudesivir    

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标题 作者 时间 类型 操作

Efficacy and safety of benralizumab in patients with eosinophilic asthma: a meta-analysis of randomized placebo-controlled trials

null

期刊论文

murine pancreatic carcinoma by β-elemene combined with dendritic cells modified with genes encoding interleukin

TAN Guang, WANG Zhongyu, CHE Luanqing, YIN Shuo

期刊论文

Keratin 5-Cre-driven deletion of

Jun Yang, Lianqing Wang, Yingzhi Huang, Keqiang Liu, Chaoxia Lu, Nuo Si, Rongrong Wang, Yaping Liu, Xue Zhang

期刊论文

Beneficial metabolic activities of inflammatory cytokine interleukin 15 in obesity and type 2 diabetes

null

期刊论文

Research on the control systems of a precision linear motor drive device

YAN Han, WANG Xian-kui, DUAN Guang-hong

期刊论文

QUANTITATIVE STUDY ON ANTI-PEST ACTIVITY OF NATURAL PRODUCTS BASED ON VISUALIZATION FRAMEWORK OF KNOWLEDGE

期刊论文

Dihydroartemisinin increased the abundance of by YAP1 depression that sensitizes hepatocellular carcinoma to anti-PD

期刊论文

Association of miRNA-122-binding site polymorphism at the interleukin-1 α gene and its interaction with

null

期刊论文

Cytokine storm and translating IL-6 biology into effective treatments for COVID-19

期刊论文

A modular cable-driven humanoid arm with anti-parallelogram mechanisms and Bowden cables

期刊论文

Anti-biofouling strategies for implantable biosensors of continuous glucose monitoring systems

期刊论文

Lignin-derived dual-function red light carbon dots for hypochlorite detection and anti-counterfeiting

期刊论文

Modulatory effect on dyslipidemia and anti-atherosclerotic function of in newly diagnosed type 2 diabetes

SUN Mingxiao, WANG Yao, CHI Jiamin

期刊论文

Preparation of reverse osmosis membrane with high permselectivity and anti-biofouling properties for

期刊论文

Small-molecule anti-COVID-19 drugs and a focus on China’s homegrown mindeudesivir (VV116)

期刊论文