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Non-genetic mechanisms of diabetic nephropathy

null

《医学前沿（英文）》 2017年 第11卷 第3期   页码 319-332 doi: 10.1007/s11684-017-0569-9

摘要：

Diabetic nephropathy (DN) is one of the most common microvascular complications in diabetes mellitus patients and is characterized by thickened glomerular basement membrane, increased extracellular matrix formation, and podocyte loss. These phenomena lead to proteinuria and altered glomerular filtration rate, that is, the rate initially increases but progressively decreases. DN has become the leading cause of end-stage renal disease. Its prevalence shows a rapid growth trend and causes heavy social and economic burden in many countries. However, this disease is multifactorial, and its mechanism is poorly understood due to the complex pathogenesis of DN. In this review, we highlight the new molecular insights about the pathogenesis of DN from the aspects of immune inflammation response, epithelial–mesenchymal transition, apoptosis and mitochondrial damage, epigenetics, and podocyte–endothelial communication. This work offers groundwork for understanding the initiation and progression of DN, as well as provides ideas for developing new prevention and treatment measures.

关键词： diabetic nephropathy     immune inflammatory response     epithelial–mesenchymal transition     apoptosis     mitochondrial damage     epigenetics     podocyte–endothelial communication    

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Metformin and metabolic diseases: a focus on hepatic aspects

null

《医学前沿（英文）》 2015年 第9卷 第2期   页码 173-186 doi: 10.1007/s11684-015-0384-0

摘要：

Metformin has been widely used as a first-line anti-diabetic medicine for the treatment of type 2 diabetes (T2D). As a drug that primarily targets the liver, metformin suppresses hepatic glucose production (HGP), serving as the main mechanism by which metformin improves hyperglycemia of T2D. Biochemically, metformin suppresses gluconeogenesis and stimulates glycolysis. Metformin also inhibits glycogenolysis, which is a pathway that critically contributes to elevated HGP. While generating beneficial effects on hyperglycemia, metformin also improves insulin resistance and corrects dyslipidemia in patients with T2D. These beneficial effects of metformin implicate a role for metformin in managing non-alcoholic fatty liver disease. As supported by the results from both human and animal studies, metformin improves hepatic steatosis and suppresses liver inflammation. Mechanistically, the beneficial effects of metformin on hepatic aspects are mediated through both adenosine monophosphate-activated protein kinase (AMPK)-dependent and AMPK-independent pathways. In addition, metformin is generally safe and may also benefit patients with other chronic liver diseases.

关键词： metformin     diabetes     hepatic steatosis     inflammatory response     insulin resistance    

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Improved dissolution and anti-inflammatory effect of ibuprofen by solid dispersion

null

《医学前沿（英文）》 2012年 第6卷 第2期   页码 195-203 doi: 10.1007/s11684-012-0189-3

摘要：

The purpose of this study was to improve the dissolution rate and anti-inflammatory effect of ibuprofen by a solid dispersion (SD) method. Initial screening was developed based on drug solubility in carriers in the liquid state to select a suitable water-soluble carrier system for the preparation of SDs. The dissolution of ibuprofen in urea was higher than in PEG4000 or mannitol. Thus, urea was selected as the carrier for the preparation of SDs. SDs were characterized in terms of dissolution, differential scanning calorimetry (DSC), X-ray diffraction (XRD), scanning electron microscopy (SEM), and Fourier transform infrared (FTIR) spectroscopy. Solid dispersion-based (SDBT) and conventional (CT) tablets were prepared by the wet granulation method. The anti-inflammatory effect of SDBT was evaluated using the mouse ear edema test with xylene. In vitro release results indicated that the ibuprofen dissolution rate was improved by the SD. SD characterization results suggested that ibuprofen partly precipitates in crystalline and amorphous forms after SD preparation and that ibuprofen and urea do not interact. SDBT displayed more significant anti-inflammatory effects than CT. The dissolution rate and anti-inflammatory effect of ibuprofen were significantly enhanced by the ibuprofen-urea SD.

关键词： ibuprofen     solid dispersion     physical mixture     dissolution     anti-inflammatory effect    

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

null

《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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Bioactive hyaluronic acid fragments inhibit lipopolysaccharide-induced inflammatory responses via the

Na You, Sasa Chu, Binggang Cai, Youfang Gao, Mizhou Hui, Jin Zhu, Maorong Wang

《医学前沿（英文）》 2021年 第15卷 第2期   页码 292-301 doi: 10.1007/s11684-020-0806-5

摘要： The high- and the low-molecular weight hyaluronic acids (HMW-HA and LMW-HA, respectively) showed different biological activities in inflammation. However, the role of LMW-HA in inflammatory response is controversial. In this study, we aimed to investigate the effect of bioactive hyaluronan (B-HA) on lipopolysaccharide (LPS)-induced inflammatory responses in human macrophages and mice. B-HA was produced from HA treated with glycosylated recombinant human hyaluronidase PH20. Human THP-1 cells were induced to differentiate into macrophages. THP-1-derived macrophages were treated with B-HA, LPS, or B-HA+LPS. The mRNA expression and the production of inflammatory cytokines were determined using quantitative real-time PCR and enzyme-linked immunosorbent assay. The phosphorylation levels of proteins in the nuclear factor- B (NF- B), mitogen-activated protein kinase (MAPK), and IRF-3 signaling pathways were measured using Western blot. The efficacy of B-HA was assessed in a mouse model of LPS-induced inflammation. Results showed that B-HA inhibited the expression of TNF-α, IL-6, IL-1, and IFN-β, and enhanced the expression of the anti-inflammatory cytokine IL-10 in LPS-induced inflammatory responses in THP-1-derived macrophages and . B-HA significantly suppressed the phosphorylation of the TLR4 signaling pathway proteins p65, IKKα/β, I Bα, JNK1/2, ERK1/2, p38, and IRF-3. In conclusion, our results demonstrated that the B-HA attenuated the LPS-stimulated inflammatory response by inhibiting the activation of the TLR4 signaling pathway. B-HA could be a potential anti-inflammatory drug in the treatment of inflammatory disease.

关键词： bioactive hyaluronan     lipopolysaccharide     inflammatory cytokines     TLR4     human macrophages    

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左炔诺孕酮宫内释放系统对胰岛素样生长因子-1的影响与预防盆腔炎的相关性研究

吴晓杰,刘霞,陶跃平,王洁

《中国工程科学》 2015年 第17卷 第6期   页码 4-7

摘要：

目的：研究左炔诺孕酮宫内释放系统对子宫内膜组织胰岛素样生长因子-1（IGF-1）的影响及预防盆腔炎疗效分析。方法：选取2010―2013年在嘉兴市妇幼保健院行宫腔镜下子宫内膜息肉切除术患者450例进行随机分组，研究组术后子宫内即时放置左炔诺孕酮宫内释放系统，而对照组不予放置。分别对术前及术后6个月子宫内膜组织IGF-1的表达情况进行对比，且随访2年，了解患者盆腔炎发生情况。结果：所有手术均成功，研究组子宫内膜组织IGF-1表达术后明显低于术前，对照组术前及术后子宫内膜组织IGF-1表达变化无差异，二组相比，术后IGF-1表达差异有显著性。随访2年对照组224例患者中39例发生盆腔炎，复发率为10.89 %，而研究组184例发生盆腔炎12例，差异有显著性；研究组子宫内膜厚度术后明显小于术前，差异有显著性，对照组子宫内膜厚度术后与术前变化无差异性。结论：左炔诺孕酮宫内释放系统对子宫内膜的IGF-1表达存在抑制作用，可能是其抑制子宫内膜增生并减少盆腔炎发生的机制之一。

关键词： 左炔诺孕酮宫内系统；胰岛素样生长因子；盆腔炎    

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Development of a seismic design method based on response spectra for building structures

ZHOU Xiyuan, YU Ruifang

《结构与土木工程前沿（英文）》 2007年 第1卷 第2期   页码 129-141 doi: 10.1007/s11709-007-0014-2

摘要： The assumption and problem of the mode-superposition response spectrum method in seismic design code is discussed based on a brief review of the development of the seismic design method for building structures. The scope of application for the classical damping theory is analyzed and the necessity of the research on mode-superposition method for non-classical damping is presented. The progresses on the mode superposition response spectrum theory are discussed. This includes: 1) the complex mode superposition method (in real form) for the non-classically damped linear system and the general calculation formula for the application of code; 2) the complex complete quadratic combination (CCQC) method for the non-classically damped linear system, which is based on the same assumptions as in deducing the complete quadratic combination (CQC) method which is popularly used in seismic design codes of many countries; 3) the complex complete quadratic combination with three components (CCQC3) method, which is a generalization of the CCQC method to the case of multi-components and multiple-support seismic excitations and deducing corresponding method; 4) the approach for calculation of seismic response of the non-classically damped system with overcritical damping and the calculation method of seismic response for the linear system with multiple eigenvalues; 5) the time-dependent CCQC (t) algorithm considering nonstationary earthquake ground motion; 6) an applied and effective method to solve the low order complex vector basis for the large linear non-classically damped system, which can be expediently used in practice to avoid the unknown errors coming from the forced uncoupling method; 7) bringing forward the concept of partial quadratic combination in order to reduce the calculation amount of CQC and CCQC methods, and studying the primary estimation-criterion. The reasonability and applicable scope of these methods are also briefly discussed in this paper.

关键词： generalization     classical damping     mode-superposition response     calculation formula     damping theory    

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Confining pressure effect on dynamic response of high rockfill dam

Xuexing CAO, Yunlong HE, Kun XIONG,

《结构与土木工程前沿（英文）》 2010年 第4卷 第1期   页码 116-126 doi: 10.1007/s11709-010-0014-5

摘要： Studies show that the dynamic properties of rockfill are strongly dependent on the confining pressure. Therefore, confining pressure effect has become a very important factor in the seismic analysis of high rockfill dam. The relationships of dynamic shear modulus versus dynamic shear strain and damping ratio versus dynamic shear strain had been improved to a certain degree on the basic of widely used Hardin-Drnevich constitutive model in this paper. Then a new model that could consider confining pressure effect has been established. Regression analysis was carried out of the dynamic triaxial experimental data of the damming materials in the Changheba hydropower station of Sichun Province, China. The results show that, the new model can fit the test data well under various confining pressures. A corresponding computational procedure was compiled and applied in the dynamic response analysis of the Changheba Dam. Comparing the calculation results between the new constitutive model and the ordinary Hardin-Drnevich model, it can be seen that the result is conservative to some extent without considering confining pressure effect.

关键词： confining pressure effect     high rockfill dam     dynamic response     Hardin-Drnevich constitutive model    

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Topology optimization of transient problem with maximum dynamic response constraint using SOAR scheme

《机械工程前沿（英文）》 2021年 第16卷 第3期   页码 593-606 doi: 10.1007/s11465-021-0636-4

摘要： This paper proposes a novel method for the continuum topology optimization of transient vibration problem with maximum dynamic response constraint. An aggregated index in the form of an integral function is presented to cope with the maximum response constraint in the time domain. The density filter solid isotropic material with penalization method combined with threshold projection is developed. The sensitivities of the proposed index with respect to design variables are conducted. To reduce computational cost, the second-order Arnoldi reduction (SOAR) scheme is employed in transient analysis. Influences of aggregate parameter, duration of loading period, interval time, and number of basis vectors in the SOAR scheme on the final designs are discussed through typical examples while unambiguous configuration can be achieved. Through comparison with the corresponding static response from the final designs, the optimized results clearly demonstrate that the transient effects cannot be ignored in structural topology optimization.

关键词： topology optimization     solid isotropic material with penalization     transient response     aggregation function     second-order Arnoldi reduction    

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Intestinal Epithelial Axin1 Deficiency Protects Against Colitis via Altered Gut Microbiota

Shari Garrett,Yongguo Zhang,Yinglin Xia,Jun Sun,

《工程（英文）》 doi: 10.1016/j.eng.2023.06.007

摘要： Intestinal homeostasis is maintained by specialized host cells and the gut microbiota. Wnt/β-catenin signaling is essential for gastrointestinal development and homeostasis, and its dysregulation has been implicated in inflammation and colorectal cancer. Axin1 negatively regulates activated Wnt/β-catenin signaling, but little is known regarding its role in regulating host–microbial interactions in health and disease. Here, we aim to demonstrate that intestinal Axin1 determines gut homeostasis and host response to inflammation. Axin1 expression was analyzed in human inflammatory bowel disease datasets. To explore the effects and mechanism of intestinal Axin1 in regulating intestinal homeostasis and colitis, we generated new mouse models with Axin1 conditional knockout in intestinal epithelial cell (IEC; Axin1ΔIEC) and Paneth cell (PC; Axin1ΔPC) to compare with control (Axin1LoxP; LoxP: locus of X-over, P1) mice. We found increased Axin1 expression in the colonic epithelium of human inflammatory bowel disease (IBD). Axin1ΔIEC mice exhibited altered goblet cell spatial distribution, PC morphology, reduced lysozyme expression, and enriched Akkermansia muciniphila (A. muciniphila). The absence of intestinal epithelial and PC Axin1 decreased susceptibility to dextran sulfate sodium-induced colitis in vivo. Axin1ΔIEC and Axin1ΔPC mice became more susceptible to dextran sulfate sodium (DSS)-colitis after cohousing with control mice. Treatment with A. muciniphila reduced DSS-colitis severity. Antibiotic treatment did not change the IEC proliferation in the Axin1Loxp mice. However, the intestinal proliferative cells in Axin1ΔIEC mice with antibiotic treatment were reduced compared with those in Axin1ΔIEC mice without treatment. These data suggest non-colitogenic effects driven by the gut microbiome. In conclusion, we found that the loss of intestinal Axin1 protects against colitis, likely driven by epithelial Axin1 and Axin1-associated A. muciniphila. Our study demonstrates a novel role of Axin1 in mediating intestinal homeostasis and the microbiota. Further mechanistic studies using specific Axin1 mutations elucidating how Axin1 modulates the microbiome and host inflammatory response will provide new therapeutic strategies for human IBD.

关键词： Axin1     Bacteria     Microbiome inflammation     Inflammatory bowel disease     Immunity     Microbiome     Paneth cells     Akkermansia muciniphila     Wnt    

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Dynamic response of precast segmental bridge columns under heavy truck impact

《结构与土木工程前沿（英文）》 2023年 第17卷 第3期   页码 327-349 doi: 10.1007/s11709-023-0911-z

摘要： Considering the wide application of precast segmental bridge columns (PSBCs) in engineering practice, impact-resistant performance has gained significant attention. However, few studies have focused on PSBCs subjected to high-energy impacts caused by heavy truck collisions. Therefore, the behavior of PSBCs under a heavy truck impact was investigated in this study using high-fidelity finite element (FE) models. The detailed FE modeling methods of the PSBCs and heavy trucks were validated against experimental tests. The validated modeling methods were employed to simulate collisions between PSBCs and heavy trucks. The simulation results demonstrated that the engine and cargo caused two major peak impact forces during collision. Subsequently, the impact force, failure mode, displacement, and internal force of the PSBCs under heavy truck impacts were scrutinized. An extensive study was performed to assess the influence of the section size, truck weight, impact velocity, and number of precast segments on the impact responses. The truck weight was found to have a minor effect on the engine impact force. Damage was found to be localized at the bottom of the three segments, with the top remaining primarily undamaged. This parametric study demonstrated that larger cross-sections may be a preferred option to protect PSBCs against the impact of heavy trucks.

关键词： precast segmental bridge columns     heavy truck     collision     dynamic response    

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Dynamic response surface methodology using Lasso regression for organic pharmaceutical synthesis

《化学科学与工程前沿（英文）》 2022年 第16卷 第2期   页码 221-236 doi: 10.1007/s11705-021-2061-y

摘要： To study the dynamic behavior of a process, time-resolved data are collected at different time instants during each of a series of experiments, which are usually designed with the design of experiments or the design of dynamic experiments methodologies. For utilizing such time-resolved data to model the dynamic behavior, dynamic response surface methodology (DRSM), a data-driven modeling method, has been proposed. Two approaches can be adopted in the estimation of the model parameters: stepwise regression, used in several of previous publications, and Lasso regression, which is newly incorporated in this paper for the estimation of DRSM models. Here, we show that both approaches yield similarly accurate models, while the computational time of Lasso is on average two magnitude smaller. Two case studies are performed to show the advantages of the proposed method. In the first case study, where the concentrations of different species are modeled directly, DRSM method provides more accurate models compared to the models in the literature. The second case study, where the reaction extents are modeled instead of the species concentrations, illustrates the versatility of the DRSM methodology. Therefore, DRSM with Lasso regression can provide faster and more accurate data-driven models for a variety of organic synthesis datasets.

关键词： data-driven modeling     pharmaceutical organic synthesis     Lasso regression     dynamic response surface methodology    

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Recent advances in myeloid-derived suppressor cell biology

Mahmoud Mohammad Yaseen, Nizar Mohammad Abuharfeil, Homa Darmani, Ammar Daoud

《医学前沿（英文）》 2021年 第15卷 第2期   页码 232-251 doi: 10.1007/s11684-020-0797-2

摘要： In recent years, studying the role of myeloid-derived suppressor cells (MDSCs) in many pathological inflammatory conditions has become a very active research area. Although the role of MDSCs in cancer is relatively well established, their role in non-cancerous pathological conditions remains in its infancy resulting in much confusion. Our objectives in this review are to address some recent advances in MDSC research in order to minimize such confusion and to provide an insight into their function in the context of other diseases. The following topics will be specifically focused upon: (1) definition and characterization of MDSCs; (2) whether all MDSC populations consist of immature cells; (3) technical issues in MDSC isolation, estimation and characterization; (4) the origin of MDSCs and their anatomical distribution in health and disease; (5) mediators of MDSC expansion and accumulation; (6) factors that determine the expansion of one MDSC population over the other; (7) the Yin and Yang roles of MDSCs. Moreover, the functions of MDSCs will be addressed throughout the text.

关键词： non-human primates (rhesus macaques)     myeloid-derived pro-inflammatory cells (MDPCs)     autoimmune disorders     alloimmune responses     pregnancy     mature MDSCs     multiple sclerosis     Yin-Yang law of MDSCs    

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Persistence of humoral and cellular immune response after SARS-CoV-2 infection: opportunities and challenges

Tangchun Wu

《医学前沿（英文）》 2020年 第14卷 第6期   页码 816-819 doi: 10.1007/s11684-020-0823-4

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Applications of thermostatically controlled loads for demand response with the proliferation of variable

Meng SONG, Wei SUN

《能源前沿（英文）》 2022年 第16卷 第1期   页码 64-73 doi: 10.1007/s11708-021-0732-5

摘要： More flexibility is desirable with the proliferation of variable renewable resources for balancing supply and demand in power systems. Thermostatically controlled loads (TCLs) attract tremendous attentions because of their specific thermal inertia capability in demand response (DR) programs. To effectively manage numerous and distributed TCLs, intermediate coordinators, e.g., aggregators, as a bridge between end users and dispatch operators are required to model and control TCLs for serving the grid. Specifically, intermediate coordinators get the access to fundamental models and response modes of TCLs, make control strategies, and distribute control signals to TCLs according the requirements of dispatch operators. On the other hand, intermediate coordinators also provide dispatch models that characterize the external characteristics of TCLs to dispatch operators for scheduling different resources. In this paper, the bottom-up key technologies of TCLs in DR programs based on the current research have been reviewed and compared, including fundamental models, response modes, control strategies, dispatch models and dispatch strategies of TCLs, as well as challenges and opportunities in future work.

关键词： thermostatically controlled load     demand response     renewable energy     power system operation    

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标题 作者 时间 类型 操作

Non-genetic mechanisms of diabetic nephropathy

null

期刊论文

Metformin and metabolic diseases: a focus on hepatic aspects

null

期刊论文

Improved dissolution and anti-inflammatory effect of ibuprofen by solid dispersion

null

期刊论文

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

null

期刊论文

Bioactive hyaluronic acid fragments inhibit lipopolysaccharide-induced inflammatory responses via the

Na You, Sasa Chu, Binggang Cai, Youfang Gao, Mizhou Hui, Jin Zhu, Maorong Wang

期刊论文

左炔诺孕酮宫内释放系统对胰岛素样生长因子-1的影响与预防盆腔炎的相关性研究

吴晓杰,刘霞,陶跃平,王洁

期刊论文

Development of a seismic design method based on response spectra for building structures

ZHOU Xiyuan, YU Ruifang

期刊论文

Confining pressure effect on dynamic response of high rockfill dam

Xuexing CAO, Yunlong HE, Kun XIONG,

期刊论文

Topology optimization of transient problem with maximum dynamic response constraint using SOAR scheme

期刊论文

Intestinal Epithelial Axin1 Deficiency Protects Against Colitis via Altered Gut Microbiota

Shari Garrett,Yongguo Zhang,Yinglin Xia,Jun Sun,

期刊论文

Dynamic response of precast segmental bridge columns under heavy truck impact

期刊论文

Dynamic response surface methodology using Lasso regression for organic pharmaceutical synthesis

期刊论文

Recent advances in myeloid-derived suppressor cell biology

Mahmoud Mohammad Yaseen, Nizar Mohammad Abuharfeil, Homa Darmani, Ammar Daoud

期刊论文

Persistence of humoral and cellular immune response after SARS-CoV-2 infection: opportunities and challenges

Tangchun Wu

期刊论文

Applications of thermostatically controlled loads for demand response with the proliferation of variable

Meng SONG, Wei SUN

期刊论文