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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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Efficacy of intelligent diagnosis with a dynamic uncertain causality graph model for rare disorders of

Dongping Ning, Zhan Zhang, Kun Qiu, Lin Lu, Qin Zhang, Yan Zhu, Renzhi Wang

《医学前沿（英文）》 2020年第14卷第4期页码 498-505 doi: 10.1007/s11684-020-0791-8

摘要： Disorders of sex development (DSD) are a group of rare complex clinical syndromes with multiple etiologies. Distinguishing the various causes of DSD is quite difficult in clinical practice, even for senior general physicians because of the similar and atypical clinical manifestations of these conditions. In addition, DSD are difficult to diagnose because most primary doctors receive insufficient training for DSD. Delayed diagnoses and misdiagnoses are common for patients with DSD and lead to poor treatment and prognoses. On the basis of the principles and algorithms of dynamic uncertain causality graph (DUCG), a diagnosis model for DSD was jointly constructed by experts on DSD and engineers of artificial intelligence. “Chaining” inference algorithm and weighted logic operation mechanism were applied to guarantee the accuracy and efficiency of diagnostic reasoning under incomplete situations and uncertain information. Verification was performed using 153 selected clinical cases involving nine common DSD-related diseases and three causes other than DSD as the differential diagnosis. The model had an accuracy of 94.1%, which was significantly higher than that of interns and third-year residents. In conclusion, the DUCG model has broad application prospects as a computer-aided diagnostic tool for DSD-related diseases.

关键词： disorders of sex development (DSD) intelligent diagnosis dynamic uncertain causality graph

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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

null

《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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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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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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Therapeutic effects of thalidomide in hematologic disorders: a review

null

《医学前沿（英文）》 2013年第7卷第3期页码 290-300 doi: 10.1007/s11684-013-0277-z

摘要：

The extensive autoimmune, anti-inflammatory, and anticancer applications of thalidomide have inspired a growing number of studies and clinical trials. As an inexpensive agent with relatively low toxicity, thalidomide is regarded as a promising therapeutic candidate, especially for malignant diseases. We review its therapeutic effects in hematology, including those on multiple myeloma, Waldenstroem macroglobulinemia, lymphoma, mantle-cell lymphoma, myelodysplastic syndrome, hereditary hemorrhagic telangiectasia, and graft-versus-host disease. Most studies have shown satisfactory results, although several have reported the opposite. Aside from optimal outcomes, the toxicities and adverse effects of thalidomide should also be examined. The current work includes a discussion of the mechanisms through which the novel biological effects of thalidomide occur, although more studies should be devoted to this aspect. With appropriate safeguards, thalidomide may benefit patients suffering from a broad variety of disorders, particularly refractory and resistant diseases.

关键词： thalidomide multiple myeloma lymphoma

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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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Mesenchymal stem cells and immune disorders: from basic science to clinical transition

Shihua Wang, Rongjia Zhu, Hongling Li, Jing Li, Qin Han, Robert Chunhua Zhao

《医学前沿（英文）》 2019年第13卷第2期页码 138-151 doi: 10.1007/s11684-018-0627-y

摘要： As a promising candidate seed cell type in regenerative medicine, mesenchymal stem cells (MSCs) have attracted considerable attention. The unique capacity of MSCs to exert a regulatory effect on immunity in an autologous/allergenic manner makes them an attractive therapeutic cell type for immune disorders. In this review, we discussed the current knowledge of and advances in MSCs, including its basic biological properties, i.e., multilineage differentiation, secretome, and immunomodulation. Specifically, on the basis of our previous work, we proposed three new concepts of MSCs, i.e., “subtotipotent stem cell” hypothesis, MSC system, and “Yin and Yang” balance of MSC regulation, which may bring new insights into our understanding of MSCs. Furthermore, we analyzed data from the Clinical Trials database (http://clinicaltrials.gov) on registered clinical trials using MSCs to treat a variety of immune diseases, such as graft-versus-host disease, systemic lupus erythematosus, and multiple sclerosis. In addition, we highlighted MSC clinical trials in China and discussed the challenges and future directions in the field of MSC clinical application.

关键词： mesenchymal stem cell clinical transition immune disorders

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Panoramic variation analysis of a family with neurodevelopmental disorders caused by biallelic loss-of-function

《医学前沿（英文）》 doi: 10.1007/s11684-023-1006-x

摘要： Highly clinical and genetic heterogeneity of neurodevelopmental disorders presents a major challenge in clinical genetics and medicine. Panoramic variation analysis is imperative to analyze the disease phenotypes resulting from multilocus genomic variation. Here, a Pakistani family with parental consanguinity was presented, characterized with severe intellectual disability (ID), spastic paraplegia, and deafness. Homozygosity mapping, integrated single nucleotide polymorphism (SNP) array, whole-exome sequencing, and whole-genome sequencing were performed, and homozygous variants in TMEM141 (c.270G>A, p.Trp90*), DDHD2 (c.411+767_c.1249-327del), and LHFPL5 (c.250delC, p.Leu84*) were identified. A Tmem141^{p.Trp90*/p.Trp90*} mouse model was generated. Behavioral studies showed impairments in learning ability and motor coordination. Brain slice electrophysiology and Golgi staining demonstrated deficient synaptic plasticity in hippocampal neurons and abnormal dendritic branching in cerebellar Purkinje cells. Transmission electron microscopy showed abnormal mitochondrial morphology. Furthermore, studies on a human in vitro neuronal model (SH-SY5Y cells) with stable shRNA-mediated knockdown of TMEM141 showed deleterious effect on bioenergetic function, possibly explaining the pathogenesis of replicated phenotypes in the cross-species mouse model. Conclusively, panoramic variation analysis revealed that multilocus genomic variations of TMEM141, DDHD2, and LHFPL5 together caused variable phenotypes in patient. Notably, the biallelic loss-of-function variants of TMEM141 were responsible for syndromic ID.

关键词： neurodevelopmental disorder autosomal recessive intellectual disability consanguinity spastic paraplegia hearing loss TMEM141

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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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Antibiotics-mediated intestinal microbiome perturbation aggravates tacrolimus-induced glucose disorders

Yuqiu Han, Xiangyang Jiang, Qi Ling, Li Wu, Pin Wu, Ruiqi Tang, Xiaowei Xu, Meifang Yang, Lijiang Zhang, Weiwei Zhu, Baohong Wang, Lanjuan Li

《医学前沿（英文）》 2019年第13卷第4期页码 471-481 doi: 10.1007/s11684-019-0686-8

摘要： Both immunosuppressants and antibiotics (ABX) are indispensable for transplant patients. However, the former increases the risk of new-onset diabetes, whereas the latter impacts intestinal microbiota (IM). It is still unclear whether and how the interaction between immunosuppressants and ABX alters the IM and thus leads to glucose metabolism disorders. This study examined the alterations of glucose and lipid metabolism and IM in mice exposed to tacrolimus (TAC) with or without ABX. We found that ABX further aggravated TAC-induced glucose tolerance and increased insulin secretion. Combined treatment resulted in exacerbated lipid accumulation in the liver. TAC-altered microbial community was further amplified by ABX administration, as characterized by reductions in phylum Firmicutes, family Lachnospiraceae, and genus . Analyses based on the metagenomic profiles revealed that ABX augmented the effect of TAC on microbial metabolic function mostly related to lipid metabolism. The altered components of gut microbiome and predicted microbial functional profiles showed significant correlation with hepatic lipid accumulation and glucose disorders. In conclusion, ABX aggravated the effect of TAC on the microbiome and its metabolic capacities, which might contribute to hepatic lipid accumulation and glucose disorders. These findings suggest that the ABX-altered microbiome can amplify the diabetogenic effect of TAC and could be a novel therapeutic target for patients.

关键词： antibiotics tacrolimus glucose disorders microbiome

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Abnormal glycosylated hemoglobin as a predictive factor for glucose metabolism disorders in antipsychotic

XU Leping, JI Juying, DUAN Yiyang, SHI Hui, ZHANG Bin, SHAO Yaqin, SUN Jian

《医学前沿（英文）》 2007年第1卷第3期页码 316-319 doi: 10.1007/s11684-007-0061-z

摘要： The aim of this study was to observe the changes in glucose metabolism after antipsychotic (APS) therapy, to note the influencing factors, as well as to discuss the relationship between the occurrence of glucose metabolism disorders of APS origin and abnormal glycosylated hemoglobin (HbAc) levels. One hundred and fifty-two patients with schizophrenia, whose fasting plasma glucose (FPG) and 2-h plasma glucose (2hPG) in the oral glucose tolerance test (2HPG) were normal, were grouped according to the HbAc levels, one normal and the other abnormal, and were randomly enrolled into risperidone, clozapine and chlorpromazine treatment for six weeks. The FPG and 2hPG were measured at the baseline and at the end of the study. In the group with abnormal HbA1c and clozapine therapy, 2HPG was higher after the study [(9.5±1.8) mmol/L] than that before the study [(7.2±1.4) mmol/L] and the difference was statistically significant (〈0.01). FPG had no statistically significant difference before and after the study in any group (〉0.05). HbAc levels and drugs contributing to 2HPG at the end of study had statistical cross-action (〈0.01). In the abnormal HbAc group, 2HPG after the study was higher in the clozapine treatment group [(9.5±1.8) mmol/L] than in the risperidone treatment group [(7.4±1.7) mmol/L] and the chlorpromazine treatment group [(7.3±1.6) mmol/L]. The differences were statistically significant (〈0.01). In the normal HbAc group there was no statistically significant difference before and after the study in any group (〉0.05). 2HPG before [(7.1±1.6) mmol/L] and after the study [(8.1±1.9) mmol/L] was higher in the abnormal HbAc group than in the normal HbAc group [(6.2±1.4) mmol/L (6.5±1.4) mmol/L] with the difference being statistically significant (〈0.01 〈0.001). As compared with normal HbAc group, the relative risk (RR) of glucose metabolism disease occurrence was 4.7 in the abnormal HbAc group with the difference being statistically significant (〈0.001). Patients with abnormal HbAc are more likely to have a higher risk of having glucose metabolism disorders after APS treatment.

关键词： significant difference occurrence hemoglobin risperidone treatment abnormal

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人工智能算法在精神疾病中的应用简述 Review

刘光迪, 李雨辰, 张伟, 章乐

《工程（英文）》 2020年第6卷第4期页码 462-467 doi: 10.1016/j.eng.2019.06.008

摘要：

为了研究精神疾病的病因和发病机制，各国开展了大量脑研究计划。尽管精神疾病是脑科学研究的重要部分，但精神疾病的诊断仍然依靠医生的主观经验，而非疾病的病理生理学指标。因此，为了开发有效的治疗方式和干预措施，我们迫切需要对重大精神疾病的病因和致病机制有一个清晰的认识。当前，人工智能（AI）技术在精神疾病的应用研究发展迅速，但缺少对其进行系统化的总结和展望。因此，本研究简要回顾了用于研究精神疾病的三种主要观测技术，即磁共振成像（MRI）、脑电图（EEG）和基于体势学的诊断（与模式识别相关的AI算法）。最后，我们讨论了AI应用面临的挑战、机遇和未来的发展方向。

关键词：人工智能精神疾病神经影像学

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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