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The critical importance of epigenetics in autoimmune-related skin diseases

《医学前沿（英文）》 2023年第17卷第1期页码 43-57 doi: 10.1007/s11684-022-0980-8

摘要： Autoimmune-related skin diseases are a group of disorders with diverse etiology and pathophysiology involved in autoimmunity. Genetics and environmental factors may contribute to the development of these autoimmune disorders. Although the etiology and pathogenesis of these disorders are poorly understood, environmental variables that induce aberrant epigenetic regulations may provide some insights. Epigenetics is the study of heritable mechanisms that regulate gene expression without changing DNA sequences. The most important epigenetic mechanisms are DNA methylation, histone modification, and noncoding RNAs. In this review, we discuss the most recent findings regarding the function of epigenetic mechanisms in autoimmune-related skin disorders, including systemic lupus erythematosus, bullous skin diseases, psoriasis, and systemic sclerosis. These findings will expand our understanding and highlight the possible clinical applications of precision epigenetics approaches.

关键词： epigenetics autoimmune-related skin diseases DNA methylation histone modifications noncoding RNAs

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Autoimmune hepatitis

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《医学前沿（英文）》 2015年第9卷第2期页码 187-219 doi: 10.1007/s11684-015-0386-y

摘要：

Autoimmune hepatitis is a chronic liver disease putatively caused by loss of tolerance to hepatocyte-specific autoantigens. It is characterized by female predilection, elevated aminotransferase levels, autoantibodies, increased γ-globulin or IgG levels and biopsy evidence of interface hepatitis. It is currently divided into types 1 and 2, based on expression of autoantibodies. Autoantigenic epitopes have been identified only for the less frequent type 2. Although autoimmune hepatitis occurs in childhood, this review focuses on disease in adults. In the absence of pathognomonic biomarkers, diagnosis requires consideration of clinical, biochemical, serological and histological features, which have been codified into validated diagnostic scoring systems. Since many features also occur in other chronic liver diseases, these scoring systems aid evaluation of the differential diagnosis. New practice guidelines have redefined criteria for remission to include complete biochemical and histological normalization on immunosuppressive therapy. Immunosuppression is most often successful using prednisone or prednisolone and azathioprine; however, the combination of budesonide and azathioprine for non-cirrhotic patients offers distinct advantages. Patients failing standard immunosuppression are candidates for alternative immunosuppressive regimens, yet none of the options has been studied in a randomized, controlled trial. Overlap syndromes with either primary sclerosing cholangitis or primary biliary cirrhosis occur in a minority. Liver transplantation represents a life-saving option for patients presenting with acute liver failure, severely decompensated cirrhosis or hepatocellular carcinoma. Transplant recipients are at risk for recurrent autoimmune hepatitis in the allograft, and de novo disease may occur in patients transplanted for other indications. Patients transplanted for AIH are also at risk for recurrent or de novo inflammatory bowel disease. Progress in our understanding of the immunopathogenesis should lead to identification of specific diagnostic and prognostic biomarkers and new therapeutic strategies.

关键词： autoimmune hepatitis autoantibodies diagnosis immunological diseases drug-induced liver injury therapy immunosuppression outcomes hepatocellular carcinoma liver transplantation

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Th17 Cells in autoimmune diseases

null

《医学前沿（英文）》 2015年第9卷第1期页码 10-19 doi: 10.1007/s11684-015-0388-9

摘要：

Th17 cells are a new subset of CD4⁺ T cells involved in the clearance of extracellular pathogens and fungi. Accumulating evidence suggests that Th17 cells and their signature cytokines have a pivotal role in the pathogenesis of multiple autoimmune-mediated inflammatory diseases. Here, we summarize recent research progress on Th17 function in the development and pathogenesis of autoimmune diseases. We also propose to identify new small molecule compounds to manipulate Th17 function for potential therapeutic application to treat human autoimmune diseases, including rheumatoid arthritis, systemic lupus erythematosus, Sj?gren’s syndrome, inflammatory bowel disease, and multiple sclerosis.

关键词： IL-17 Th17 cells RORγt autoimmune diseases posttranslational modification inhibitors

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γδ T cells in liver diseases

null

《医学前沿（英文）》 2018年第12卷第3期页码 262-268 doi: 10.1007/s11684-017-0584-x

摘要：

γδ T cells display unique developmental, distributional, and functional patterns and can rapidly respond to various insults and contribute to diverse diseases. Different subtypes of γδ T cells are produced in the thymus prior to their migration to peripheral tissues. γδ T cells are enriched in the liver and exhibit liver-specific features. Accumulating evidence reveals that γδ T cells play important roles in liver infection, non-alcoholic fatty liver disease, autoimmune hepatitis, liver fibrosis and cirrhosis, and liver cancer and regeneration. In this study, we review the properties of hepatic γδ T cells and summarize the roles of γδ T cells in liver diseases. We believe that determining the properties and functions of γδ T cells in liver diseases enhances our understanding of the pathogenesis of liver diseases and is useful for the design of novel γδ T cell-based therapeutic regimens for liver diseases.

关键词： γδT cells liver infection non-alcoholic fatty liver disease autoimmune hepatitis liver fibrosis and cirrhosis liver cancer liver regeneration

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NKT cells in liver diseases

null

《医学前沿（英文）》 2018年第12卷第3期页码 249-261 doi: 10.1007/s11684-018-0622-3

摘要：

Natural killer T cells are innate-like and tissue-resident lymphocytes, which recognize lipid antigens and are enriched in the liver. Natural killer T cells play important roles in infections, tumors, autoimmune diseases, and metabolic diseases. In this study, we summarize recent findings on biology of natural killer T cells and their roles in hepatitis B virus and hepatitis C virus infection, autoimmune liver diseases, alcoholic liver disease, nonalcoholic fatty liver disease, and hepatocellular carcinoma. Controversial results from previous studies are discussed, and indicate the dynamic alteration in the role of natural killer T cells during the progression of liver diseases, which might be caused by changes in natural killer T subsets, factors skewing cytokine responses, and intercellular crosstalk between natural killer T cells and CD1d-expressing cells or bystander cells.

关键词： natural killer T cells hepatitis B virus and hepatitis C virus infection autoimmune liver diseases alcoholic liver disease nonalcoholic fatty liver disease hepatocellular carcinoma

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Primary cilia in hard tissue development and diseases

《医学前沿（英文）》 2021年第15卷第5期页码 657-678 doi: 10.1007/s11684-021-0829-6

摘要： Bone and teeth are hard tissues. Hard tissue diseases have a serious effect on human survival and quality of life. Primary cilia are protrusions on the surfaces of cells. As antennas, they are distributed on the membrane surfaces of almost all mammalian cell types and participate in the development of organs and the maintenance of homeostasis. Mutations in cilium-related genes result in a variety of developmental and even lethal diseases. Patients with multiple ciliary gene mutations present overt changes in the skeletal system, suggesting that primary cilia are involved in hard tissue development and reconstruction. Furthermore, primary cilia act as sensors of external stimuli and regulate bone homeostasis. Specifically, substances are trafficked through primary cilia by intraflagellar transport, which affects key signaling pathways during hard tissue development. In this review, we summarize the roles of primary cilia in long bone development and remodeling from two perspectives: primary cilia signaling and sensory mechanisms. In addition, the cilium-related diseases of hard tissue and the manifestations of mutant cilia in the skeleton and teeth are described. We believe that all the findings will help with the intervention and treatment of related hard tissue genetic diseases.

关键词： primary cilia bone mechanical sensing hard tissue cilium-related bone disease tooth

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Deformation analysis of shape memory polymer for morphing wing skin under airflow

Weilong YIN, Jingcang LIU, Jinsong LENG,

《机械工程前沿（英文）》 2009年第4卷第4期页码 447-449 doi: 10.1007/s11465-009-0062-5

摘要： The method for analyzing the out-of-plane deformation of a flexible skin under airflow is developed in this paper. The aerodynamic analysis is performed using the CFD software, and the structural analysis is performed using finite element method. The chief aim of the present study is to investigate the out-of-plane deformation of the shape memory polymer (SMP) skin at different temperatures. Numerical results show that the maximum out-of-plane displacement of the SMP skin increases with increasing temperature. When the SMP skin is heated to 53°C, the maximum out-of-plane displacement is about 7 mm. It decreases by 72%, when the SMP skin is applied with a uniform pre-strain of 0.1.

关键词： aircraft morphing skin shape memory polymer (SMP) deformation pre-strain

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一种基于血液检测的诊断和预测HBV相关疾病的弹性方法 Article

侯格格, 陈云茹, 刘小静, 张东, 耿智敏, 司书宾

《工程（英文）》 2024年第32卷第1期页码 174-185 doi: 10.1016/j.eng.2023.06.013

摘要：

乙肝病毒(HBV)感染威胁着全球公共卫生安全，是导致肝脏相关疾病发病率和死亡率的主要原因。HBV持续感染引起的肝脏疾病检查方法包括实验室检测、超声、CT、核磁共振和肝活检等，重复的检查和多次诊断可能导致患者每次就医都面临高额费用。因此，迫切需要建立一种经济有效的诊断方法简化乙肝相关疾病的医疗流程。基于临床血液检测，我们构建复杂网络模型并定义功能恢复力评价指标，可以帮助医生评估患者的肝脏状况。其次，通过结合网络模型和动力学，发现导致患者向肝硬化或肝癌转化的关键血液指标及其相应的阈值，为进一步研究疾病临界状态和预防疾病恶化提供思路。结果表明功能恢复力的诊断宏观平均精度为84.74%，而在没有影像或活检辅助的情况下医生凭经验诊断的宏观平均精度为55.64%。从经济角度，与一般诊断方法相比，功能恢复力可以为大多数中国患者每次就诊节省至少30美元，为大多数美国患者节省至少400美元。在全球范围内，每年将节省至少105亿美元。因此，功能恢复力可以全面评估患者的肝脏状况，减少影像学检查的次数，避免肝病诊断过程中医疗资源的浪费。

关键词： HBV相关疾病功能弹性医疗资源利用率关键状态网络

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Human menstrual blood-derived stem cells alleviate autoimmune hepatitis via JNK/MAPK signaling pathway

《医学前沿（英文）》 2023年第17卷第3期页码 534-548 doi: 10.1007/s11684-022-0953-y

摘要： Autoimmune hepatitis (AIH) is a severe globally distributed liver disease that could occur at any age. Human menstrual blood-derived stem cells (MenSCs) have shown therapeutic effect in acute lung injury and liver failure. However, their role in the curative effect of AIH remains unclear. Here, a classic AIH mouse model was constructed through intravenous injection with concanavalin A (Con A). MenSCs were intravenously injected while Con A injection in the treatment groups. The results showed that the mortality by Con A injection was significantly decreased by MenSCs treatment and liver function tests and histological analysis were also ameliorated. The results of phosphoproteomic analysis and RNA-seq revealed that MenSCs improved AIH, mainly by apoptosis and c-Jun N-terminal kinase/mitogen-activated protein signaling pathways. Apoptosis analysis demonstrated that the protein expression of cleaved caspase 3 was increased by Con A injection and reduced by MenSCs transplantation, consistent with the TUNEL staining results. An AML12 co-culture system and JNK inhibitor (SP600125) were used to verify the JNK/MAPK and apoptosis signaling pathways. These findings suggested that MenSCs could be a promising strategy for AIH.

关键词： autoimmune hepatitis (AIH) concanavalin A (Con A) human menstrual blood-derived stem cells (MenSCs) apoptosis mitogen-activated protein kinase (MAPK)

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Hyperthermia on skin immune system and its application in the treatment of human papillomavirus-infectedskin diseases

null

《医学前沿（英文）》 2014年第8卷第1期页码 1-5 doi: 10.1007/s11684-014-0309-3

摘要：

Hyperthermia is a condition characterized by increased body temperature as a consequence of failed thermoregulation. Hyperthermia occurs when a body produces or absorbs more heat than it dissipates. Hyperthermia also elicits various effects on the physiology of living cells. For instance, fever-range temperature (39β°C to 40β°C) can modulate the activities of immune cells, including antigen-presenting cells, T cells, and natural killer cells. Heat shock temperature (41β°C to 43β°C) can increase the immunogenicity of tumor cells. Cytotoxic temperature (>43β°C) can create an antigen source to induce an anti-tumor immune response. The immunomodulatory effect of hyperthermia has promoted an interest in hyperthermia-aided immunotherapy, particularly against tumors. Hyperthermia has also been used to treat deep fungal, bacterial, and viral skin infections. We conducted a series of open or controlled trials to treat skin human papillomavirus infection by inducing local hyperthermia. More than half of the patients were significantly cured compared with those in the control trial. A series of challenging clinical cases, such as large lesions in pregnant patients or patients with diabetes mellitus, were also successfully and safely managed using the proposed method. However, further studies should be conducted to clarify the underlying mechanisms and promote the clinical applications of hyperthermia.

关键词： hyperthermia HPV immune response virus tumor

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Risk stratification system for skin and soft tissue infections after allogeneic hematopoietic stem cell

《医学前沿（英文）》 2022年第16卷第6期页码 957-968 doi: 10.1007/s11684-021-0910-1

摘要： Skin and soft tissue infections (SSTIs) refer to infections involving the skin, subcutaneous tissue, fascia, and muscle. In transplant populations with hematological malignancies, an immunocompromised status and the routine use of immunosuppressants increase the risk of SSTIs greatly. However, to date, the profiles and clinical outcomes of SSTIs in hematopoietic stem cell transplantation (HSCT) patients remain unclear. This study included 228 patients (3.67%) who developed SSTIs within 180 days after allogeneic HSCT from January 2004 to December 2019 in Peking University People’s Hospital. The overall annual survival rate was 71.5%. We compared the differences between survivors and non-survivors a year after transplant and found that primary platelet graft failure (PPGF), comorbidities of acute kidney injury (AKI), and hospital-acquired pneumonia (HAP) were independent risk factors for death in the study population. A PPGF–AKI–HAP risk stratification system was established with a mortality risk score of 1×PPGF+1×AKI+1×HAP. The areas under the curves of internal and external validation were 0.833 (95% CI 0.760–0.906) and 0.826 (95% CI 0.715–0.937), respectively. The calibration plot revealed the high consistency of the estimated risks, and decision curve analysis showed considerable net benefits for patients.

关键词： skin and soft tissue infections hematopoietic stem cell transplantation risk stratification system mortality

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Numerical study of thermal characteristics of double skin facade system with middle shade

Shaoning LIU, Xiangfei KONG, Hua YANG, Minchao FAN, Xin ZHAN

《能源前沿（英文）》 2021年第15卷第1期页码 222-234 doi: 10.1007/s11708-017-0480-8

摘要： Architectural shade is an effective method for improving building energy efficiency. A new shade combined with the double skin façade (DSF) system, called middle shade (MS), was introduced and developed for buildings. In this paper, a 3D dynamic simulation was conducted to analyze the influence of MS combined with DSF on the indoor thermal characteristics. The research on MS for DSF involves the temperature, the ventilation rate, the velocity distribution of the air flow duct, and the indoor temperature. The results show that the angle and position of the shade in the three seasons are different, and different conditions effectively enhance the indoor thermal characteristics. In summer, the appearance of MS in DSF makes the indoor temperature significantly lower. The indoor temperature is obviously lower than that of the air flow duct, and the temperature of the air flow duct is less affected by MS. The influence of the position of blinds on indoor temperature and ventilation rate is greater than the influence of the angle of blinds. According to the climate characteristics of winter and transition season, in winter, early spring, and late autumn, the indoor temperature decreases with the increase of the position of blinds at daytime, but the opposite is true at night. The results found in this paper can provide reference for the design and use of MS combined with DSF in hot summer and cold winter zone.

关键词： middle shade position thermal characteristics double skin facade

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Diagnostic criteria of latent autoimmune diabetes in adults (LADA): a review and reflection

Yu Liao, Yufei Xiang, Zhiguang Zhou

《医学前沿（英文）》 2012年第6卷第3期页码 243-247 doi: 10.1007/s11684-012-0201-y

摘要： Diabetes has become a major public health problem in China nowadays. There are almost 97 million diabetic patients nationwide. Latent autoimmune diabetes in adults (LADA) is a subtype of autoimmune diabetes. Although it has been reported for about 20 years, the diagnostic criteria of this disease remain controversial. The discussion mainly focused on serum autoantibodies, period of insulin need and age of diagnosis. Besides, β cell function, metabolic parameters, genetic factors and cell immunity may also contribute to the formulation of the criteria. Here, we aim to review and discuss the diagnostic criteria of latent autoimmune diabetes in adults.

关键词： LADA diagnostic criteria autoantibodies insulin independence age of diagnosis

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Moment-curvature relationship of FRP-concrete-steel double-skin tubular members

Mingxue LIU, Jiaru QIAN

《结构与土木工程前沿（英文）》 2009年第3卷第1期页码 25-31 doi: 10.1007/s11709-009-0012-7

摘要： Tests were conducted on 3 specimens to study the flexural behavior of fiber reinforced polymer (FRP)-concrete-steel double-skin tubular members (DSTMs). The strip method was used to calculate the section moment-curvature curves of the 3 specimens and 12 models. A theoretical formula is presented for the flexural strength of DSTMs. The test results show that the tension zone of the specimen FRP tubes was in hoop compression while the compression zone was in hoop tension. The load-carrying capacity did not decrease even when the mid-span deflection reached about 1/24 of the span length. The tests, simulation and theoretical analysis resulted in a simplified formula for the flexural strength of DSTMs and a tri-linear moment-curvature model was expressed as a function of the section bending stiffness for DSTMs.

关键词： fiber reinforced polymer (FRP) concrete steel double-skin tubular members (DSTMs) moment-curvature curve flexural strength

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Analysis of effect of different construction methods of piles on the end effect on skin friction of piles

ZHOU Hongbo, CHEN Zhuchang

《结构与土木工程前沿（英文）》 2007年第1卷第4期页码 458-463 doi: 10.1007/s11709-007-0062-7

摘要： Based on the comparative analysis of end effect on skin friction of displacement-pile (driven pile), the end effect on skin friction of bored pile is studied. The end effect on skin friction between driven pile and bored pile is different and the end effect on skin friction of bored pile is reduce of skin friction in the soil layer adjacent to the pile end. The degradation degree of skin friction is deduced with the increase of the distance from pile end. The concept of additional mud cake formed by the effect of cushion at the bottom of borehole during pouring concrete is introduced to explain the mechanism of end effect on skin friction of the bored pile. The test results of post-grouting piles indicate that the post-grouting technique is an effective way to improve the end effect on skin friction of bored pile.

关键词： distance different concept additional bottom