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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

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《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

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《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

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《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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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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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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Autoimmune regulator regulates autophagy in THP-1 human monocytes

Liang SHI, Li-Hua HU, Yi-Rong LI

《医学前沿（英文）》 2010年第4卷第3期页码 336-341 doi: 10.1007/s11684-010-0096-4

摘要： The autoimmune regulator (AIRE) is a crucial factor for the induction of central tolerance, and mutations in this gene lead to abnormal immune responses. However, the role of AIRE in autophagy in immune cells, especially in monocytes, is obscure. In the present study, we found that overexpression of AIRE in THP-1 human monocytes resulted in increased endogenous light chain 3 (LC3)-II level and elevated LC3 positive vesicles. Moreover, an autophagy inhibitor or knockdown of AIRE by small interference RNA attenuated these effects. In contrast, the expression of p62/SQSTM1 remained unchanged in THP-1 cells after the corresponding treatment. Our findings indicate that AIRE plays a role in the regulation of autophagy in THP-1 human monocytes.

关键词： autoimmune regulator autophagy monocytes light chain 3 (LC3)

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Laparoscopic treatment of liver diseases in children

Jia Wei, Jiexiong Feng

《医学前沿（英文）》 2011年第5卷第4期页码 388-394 doi: 10.1007/s11684-011-0165-3

摘要： Laparoscopic liver surgery has been increasingly used for the treatment of pediatric liver diseases over the past decade due to the development of special laparoscopic instruments and improvements in the technique. A number of factors are considered when electing to undergo the surgical process, including age, type of liver disease, and so on. Especially in children with liver masses, the number of trocars used and the position of their placement must be carefully designed to achieve successful outcomes. In the current review, the application of various laparoscopic instruments and the methods used for the laparoscopic treatment of liver diseases in children over the past decade are summarized.

关键词： laparoscopic surgery liver mass pediatric

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Prevalence of cardiovascular diseases in China

Jun-Jie XIAO MD, Yi-Han CHEN MD, PhD,

《医学前沿（英文）》 2010年第4卷第1期页码 16-20 doi: 10.1007/s11684-010-0007-8

摘要： Cardiovascular diseases (CVD) cause one third of all deaths in China, and the number is anticipated to double by 2020. They also greatly result in disability and adjusted life year loss. The prevalence of CVD has become a new burden for China, due to an aging population, smoking, and changes in dietary habits and lifestyles. As the largest developing country, China needs to tailor her own national policies for managing CVD with full consideration of epidemiology, local needs, and affordability. Smoking cessation, increased physical activity, control of hypertension and hypercholesterolemia, and maintenance of a “traditional Chinese” diet should be important strategies for reducing the burden of CVD in China. Health officials in China should take their responsibilities to implement educational and preventive measures seriously.

关键词： cardiovascular diseases prevalence China risk factors prevention

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Cultural differences define diagnosis and genomic medicine practice: implications for undiagnosed diseases

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《医学前沿（英文）》 2013年第7卷第3期页码 389-394 doi: 10.1007/s11684-013-0281-3

摘要：

Despite the current acceleration and increasing leadership of Chinese genetics research, genetics and its clinical application have largely been imported to China from the Occident. Neither genetics nor the scientific reductionism underpinning its clinical application is integral to the traditional Chinese worldview. Given that disease concepts and their incumbent diagnoses are historically derived and culturally meaningful, we hypothesize that the cultural expectations of genetic diagnoses and medical genetics practice differ between the Occident and China. Specifically, we suggest that an undiagnosed diseases program in China will differ from the recently established Undiagnosed Diseases Program at the United States National Institutes of Health; a culturally sensitive concept will integrate traditional Chinese understanding of disease with the scientific reductionism of Occidental medicine.

关键词： genetics cultural differences undiagnosed diseases program

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Diagnosis and therapy of lacrimal system diseases by micro lacrimal endoscope

Nan XIANG, Weikun HU, Jing YUAN, Guigang LI, Haixia LIU

《医学前沿（英文）》 2009年第3卷第1期页码 113-117 doi: 10.1007/s11684-009-0001-1

摘要： The lacrimal endoscope is applied to the diagnosis and therapy of the disorders of the lacrimal system in combination with laser or micro drills under orthophoria. The changes of mucous membranes, the characteristics of pathological changes and the predilection sites of lacrimal system diseases were initially approached. One hundred and forty six pairs of eyes of 128 patients with lacrimal system disease were observed by the lacrimal endoscope in the Ophthalmology Department of Tongji Hospital from June 2006 to March 2007. The dynamic changes in mucous membranes, lesion sites, secreted substances and formation of membrane could be observed under orthophoria. Combined with laser or micro drill, the endoscope was applied to the therapy of lacrimal system disorders and the difference before and after the treatment was observed. Results are as follows: (1) The examination and therapy using the lacrimal endoscope were completed under topical anesthesia in 122 patients, and 6 patients of neonatorum dacryocystitis were examined and treated under general anaesthesia. All patients reported painless. (2) Sharp images of the lacrimal system were obtained by the endoscope. Normal lacrimal mucosal membrane was smooth and light pink, expanded and unobstructed during irrigation. In chronic dacryocystitis patients, the inhomogeneous colour of mucosal membranes was red and white, with different degrees of fibrotic membranes at the superior, middle and inferior parts of the nasolacrimal canals and secreted substances at sac could be observed. The lacrimal ducts could not be expanded and obstructed during irrigation. The patients with lacrimal system obstruction had different extents of membrane formation, and stenosis or complete obstruction of the lacrimal duct could be observed, and the corresponding mucosal membrane was not smooth which could not be expanded and obstructed during irrigation. (3) After the treatment by the endoscope combined with laser or micro drill, the major proliferation of the membrane disappeared and the lacrimal duct was unobstructed during irrigation. The cure rate and effective rate were 80.1% and 93.1%, respectively. The lacrimal endoscope is a new method in the diagnosis of lacrimal system diseases. Through a combination with laser or micro drill to carry out the therapy under orthophoria, it will bring a great change to the diagnosis and therapy of lacrimal system diseases.

关键词： lacrimal apparatus diseases endoscopes

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Responses to emerging and re-emerging infectious diseases: One world, One health

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《医学前沿（英文）》 2018年第12卷第1期页码 1-2 doi: 10.1007/s11684-018-0619-y

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国外重大慢性非传染性疾病防治对策研究

张祝琴,刘德培

《中国工程科学》 2017年第19卷第2期页码 112-116 doi: 10.15302/J-SSCAE-2017.02.019

摘要：

重大慢性非传染性疾病包括心脑血管疾病、癌症、呼吸系统疾病、糖尿病等，其流行给全球居民健康造成了重大威胁。为进一步对慢性病进行有效预防控制，促进健康、推动经济和社会发展，2014年中国工程院立项并开展了“重大慢性非传染性疾病防治的国际对比研究”项目，对国内外慢性病预防控制情况以及可供我们借鉴的经验进行了详细分析。本文从慢性病发病概况入手，分析了各种疾病的预防控制措施，并对不同国家的慢性病预防控制体系进行比较，凝练有益经验和方法，提出了增强我国慢性病预防控制的措施和建议。

关键词：慢性病心脑血管疾病癌症呼吸系统疾病糖尿病疾病预防控制体系

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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