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Cross-sectional network analysis of plasma proteins/metabolites correlated with pathogenesis and therapeutic

《医学前沿（英文）》 doi: 10.1007/s11684-023-1022-x

摘要： The treatment of PML/RARA+ acute promyelocytic leukemia (APL) with all-trans-retinoic acid and arsenic trioxide (ATRA/ATO) has been recognized as a model for translational medicine research. Though an altered microenvironment is a general cancer hallmark, how APL blasts shape their plasma composition is poorly understood. Here, we reported a cross-sectional correlation network to interpret multilayered datasets on clinical parameters, proteomes, and metabolomes of paired plasma samples from patients with APL before or after ATRA/ATO induction therapy. Our study revealed the two prominent features of the APL plasma, suggesting a possible involvement of APL blasts in modulating plasma composition. One was characterized by altered secretory protein and metabolite profiles correlating with heightened proliferation and energy consumption in APL blasts, and the other featured APL plasma-enriched proteins or enzymes catalyzing plasma-altered metabolites that were potential trans-regulatory targets of PML/RARA. Furthermore, results indicated heightened interferon-gamma signaling characterizing a tumor-suppressing function of the immune system at the first hematological complete remission stage, which likely resulted from therapy-induced cell death or senescence and ensuing supraphysiological levels of intracellular proteins. Overall, our work sheds new light on the pathophysiology and treatment of APL and provides an information-rich reference data cohort for the exploratory and translational study of leukemia microenvironment.

关键词： acute promyelocytic leukemia     plasma proteomics     plasma metabolomics     cross-sectional correlation network     pathogenesis     treatment    

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Obesity-related glomerulopathy: pathogenesis, pathologic, clinical characteristics and treatment

null

《医学前沿（英文）》 2017年 第11卷 第3期   页码 340-348 doi: 10.1007/s11684-017-0570-3

摘要：

In light of the rapid increase in the number of obesity incidences worldwide, obesity has become an independent risk factor for chronic kidney disease. Obesity-related glomerulopathy (ORG) is characterized by glomerulomegaly in the presence or absence of focal and segmental glomerulosclerosis lesions. IgM and complement 3 (C3) nonspecifically deposit in lesions without immune-complex-type deposits during ORG immunofluorescence. ORG-associated glomerulomegaly and focal and segmental glomerulosclerosis can superimpose on other renal pathologies. The mechanisms under ORG are complex, especially hemodynamic changes, inflammation, oxidative stress, apoptosis, and reduced functioning nephrons. These mechanisms synergize with obesity to induce end-stage renal disease. A slow increase of subnephrotic proteinuria (<3.5 g/d) is the most common clinical manifestation of ORG. Several treatment methods for ORG have been developed. Of these methods, renin–angiotensin–aldosterone system blockade and weight loss are proven effective. Targeting mitochondria may offer a novel strategy for ORG therapy. Nevertheless, more research is needed to further understand ORG.

关键词： obesity-related glomerulopathy     pathogenesis     pathologic     clinical characteristics    

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Epidemiology, pathogenesis, and management of coronavirus disease 2019-associated stroke

《医学前沿（英文）》 doi: 10.1007/s11684-023-1041-7

摘要： The coronavirus disease 2019 (COVID-19) epidemic has triggered a huge impact on healthcare, socioeconomics, and other aspects of the world over the past three years. An increasing number of studies have identified a complex relationship between COVID-19 and stroke, although active measures are being implemented to prevent disease transmission. Severe COVID-19 may be associated with an increased risk of stroke and increase the rates of disability and mortality, posing a serious challenge to acute stroke diagnosis, treatment, and care. This review aims to provide an update on the influence of COVID-19 itself or vaccines on stroke, including arterial stroke (ischemic stroke and hemorrhagic stroke) and venous stroke (cerebral venous thrombosis). Additionally, the neurovascular mechanisms involved in SARS-CoV-2 infection and the clinical characteristics of stroke in the COVID-19 setting are presented. Evidence on vaccinations, potential therapeutic approaches, and effective strategies for stroke management has been highlighted.

关键词： SARS-CoV-2     ischemic stroke     stroke     hemorrhagic stroke     cerebral venous thrombosis     vaccination    

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Various brain-eating amoebae: the protozoa, the pathogenesis, and the disease

《医学前沿（英文）》 2021年 第15卷 第6期   页码 842-866 doi: 10.1007/s11684-021-0865-2

摘要： Among various genera of free-living amoebae prevalent in nature, some members are identified as causative agents of human encephalitis, in which Naegleria fowleri followed by Acanthamoeba spp. and Balamuthia mandrillaris have been successively discovered. As the three dominant genera responsible for infections, Acanthamoeba and Balamuthia work as opportunistic pathogens of granulomatous amoebic encephalitis in immunocompetent and immunocompromised individuals, whereas Naegleria induces primary amoebic meningoencephalitis mostly in healthy children and young adults as a more violent and deadly disease. Due to the lack of typical symptoms and laboratory findings, all these amoebic encephalitic diseases are difficult to diagnose. Considering that subsequent therapies are also affected, all these brain infections cause significant mortality worldwide, with more than 90% of the cases being fatal. Along with global warming and population explosion, expanding areas of human and amoebae activity in some regions lead to increased contact, resulting in more serious infections and drawing increased public attention. In this review, we summarize the present information of these pathogenic free-living amoebae, including their phylogeny, classification, biology, and ecology. The mechanisms of pathogenesis, immunology, pathophysiology, clinical manifestations, epidemiology, diagnosis, and therapies are also discussed.

关键词： free-living amoebae     central nervous system infection     primary amoebic meningoencephalitis     granulomatous amoebic encephalitis    

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MicroRNAs and lung cancers: from pathogenesis to clinical implications

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《医学前沿（英文）》 2012年 第6卷 第2期   页码 134-155 doi: 10.1007/s11684-012-0188-4

摘要：

Lung cancer is the leading cause of cancer-related deaths in the US and worldwide. Better understanding of the disease is warranted for improvement in clinical management. Here we summarize the functions of small-RNA-based, posttranscriptional gene regulators, i.e. microRNAs, in the pathogenesis of lung cancers. We discuss the microRNAs that play oncogenic as well as tumor suppressive roles. We also touch on the value of microRNAs as markers for diagnosis, prognosis and the promising field of microRNA-based novel therapies for lung cancers.

关键词： lung biology     lung cancer     microRNA    

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Advances in COVID-19: the virus, the pathogenesis, and evidence-based control and therapeutic strategies

Guangbiao Zhou, Saijuan Chen, Zhu Chen

《医学前沿（英文）》 2020年 第14卷 第2期   页码 117-125 doi: 10.1007/s11684-020-0773-x

摘要： Since the outbreak of the COVID-19 pandemic in early December 2019, 81 174 confirmed cases and 3242 deaths have been reported in China as of March 19, 2020. The Chinese people and government have contributed huge efforts to combat this disease, resulting in significant improvement of the situation, with 58 new cases (34 were imported cases) and 11 new deaths reported on March 19, 2020. However, as of March 19, 2020, the COVID-19 pandemic continues to develop in 167 countries/territories outside of China, and 128 665 confirmed cases and 5536 deaths have been reported, with 16 498 new cases and 817 new deaths occurring in last 24 hours. Therefore, the world should work together to fight against this pandemic. Here, we review the recent advances in COVID-19, including the insights in the virus, the responses of the host cells, the cytokine release syndrome, and the therapeutic approaches to inhibit the virus and alleviate the cytokine storm. By sharing knowledge and deepening our understanding of the virus and the disease pathogenesis, we believe that the community can efficiently develop effective vaccines and drugs, and the mankind will eventually win this battle against this pandemic.

关键词： COVID-19     SARS-CoV-2     pathogenesis     evidence-based medicine     control and therapeutic strategies    

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Molecular pathogenesis of acute myeloid leukemia: A diverse disease with new perspectives

Felicitas THOL, Arnold GANSER

《医学前沿（英文）》 2010年 第4卷 第4期   页码 356-362 doi: 10.1007/s11684-010-0220-5

摘要： Acute myeloid leukemia (AML) is a very heterogeneous neoplasm of the hematopoietic stem cell. Despite important achievements in the treatment of AML, the long term survival of patients with the disease remains poor. Understanding the pathogenesis of AML better is crucial for finding new treatment approaches. During AML development hematopoietic precursor cells undergo clonal transformation in a multistep process through acquisition of chromosomal rearrangements and/or different gene mutations. Over recent years, novel gene mutations have been found in patients with AML. These mutations can be divided into two important categories, class I mutations that confer a proliferation advantage and class II mutations that inhibit myeloid differentiation. Screening for some of these mutations is now part of the initial diagnostic work-up in newly diagnosed AML patients. Information about the mutation status of specific genes is useful for risk-stratification, minimal residual disease (MRD) monitoring and increasingly also for targeted therapy, especially for patients with cytogenetically normal AML (CN-AML). Besides chromosomal rearrangements and gene mutations, epigenetic regulation of genes – meaning changes in gene expression by mechanisms other than changes in the underlying DNA sequence – also represents an important mechanism of leukemogenesis. This article reviews some of the most common mutations in CN-AML and gives a perspective of the translation of these discoveries from bench to bedside.

关键词： acute myeloid leukemia     mutations     risk stratification    

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Pathogenesis, diagnosis, and treatment of recurrent spontaneous abortion with immune type

Qi-De LIN, Li-Hua QIU

《医学前沿（英文）》 2010年 第4卷 第3期   页码 275-279 doi: 10.1007/s11684-010-0101-y

摘要： Recurrent spontaneous abortion (RSA), defined as three or more consecutive pregnancy losses before 20 weeks of gestation, is difficult to treat in the clinical setting. It affects 1%–5% of women of reproductive age. In the investigations of immunopathogenesis, diagnosis, and treatment of RSA since the late 1980s, it was found that RSA was associated with abnormal maternal local or systemic immune response. The pathogenesis of autoimmune RSA was mainly associated with antiphospholipid antibody (APA), while that of alloimmune RSA was due to the disturbance of maternofetal immunological tolerance. Systemic etiological screening process and diagnosis systems of RSA with immune type were developed, and anticardiolipin (ACL or ACA) + anti-β2-GP1 antibody combining multiple assays for effective diagnosis of RSA with autoimmune type was first established. According to the dynamic monitoring of clinical parameters before and during gestation, low-dose, short-course, and individual immunosuppressive therapy and lymphocyte immunotherapy for RSA with immune type were carried out. The outcomes of the offsprings of patients with RSA were followed up, and the safety and validity of the therapies were confirmed. The research achievement leads to great progress in the diagnosis and treatment of RSA in China.

关键词： spontaneous abortion     recurrent     autoimmune     alloimmune     pathogenesis     diagnosis     immunotherapy    

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Toll-like receptor signaling in hematopoietic homeostasis and the pathogenesis of hematologic diseases

null

《医学前沿（英文）》 2015年 第9卷 第3期   页码 288-303 doi: 10.1007/s11684-015-0412-0

摘要：

Toll-like receptors (TLRs), which are found in innate immune cells, are essential mediators of rapid inflammatory responses and appropriate T-cell activation in response to infection and tissue damage. Accumulating evidence suggests that TLR signaling is involved in normal hematopoiesis and specific hematologic pathologies. Particular TLRs and their downstream signaling mediators are expressed not only in terminally differentiated innate immune cells but also in early hematopoietic progenitors. Sterile activation of TLR signaling is required to generate early embryonic hematopoietic progenitor cells. In adult animals, TLR signaling directly or indirectly promotes differentiation of myeloid cells at the expense of that of lymphoid cells and the self-renewal of hematopoietic stem cells during infection and tissue damage. Activating mutations of the MyD88 gene, which codes for a key adaptor involved in TLR signaling, are commonly detected in B-cell lymphomas and other B-cell hematopathologies. Dysregulated TLR signaling contributes to the pathogenesis of many hematopoietic disorders, including bone marrow failure, myelodysplastic syndrome, and acute myeloid leukemia. Complete elucidation of the molecular mechanisms by which TLR signaling mediates the regulation of both normal and pathogenic hematopoiesis will prove valuable to the development of targeted therapies and strategies for improved treatment of hematopoietic disorders.

关键词： TLR     MyD88     hematopoiesis     bone marrow failure     leukemia     myelodysplastic syndrome    

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AML1-ETO driven acute leukemia: insights into pathogenesis and potential therapeutic approaches

null

《医学前沿（英文）》 2012年 第6卷 第3期   页码 248-262 doi: 10.1007/s11684-012-0206-6

摘要：

The AML1-ETO fusion transcription factor is generated by the t(8;21) translocation, which is present in approximately 4%–12% of adult and 12%–30% of pediatric acute myeloid leukemia (AML) patients. Both human and mouse models of AML have demonstrated that AML1-ETO is insufficient for leukemogenesis in the absence of secondary events. In this review, we discuss the pathogenetic insights that have been gained from identifying the various events that can cooperate with AML1-ETO to induce AML in vivo. We also discuss potential therapeutic strategies for t(8;21) positive AML that involve targeting the fusion protein itself, the proteins that bind to it, or the genes that it regulates. Recently published studies suggest that a targeted therapy for t(8;21) positive AML is feasible and may be coming sometime soon.

关键词： AML1-ETO     mouse model     leukemia     t(8     21)     pathway hits     mutation     hematopoiesis     Kasumi-1     CD34+    

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Increased expression of coronin-1a in amyotrophic lateral sclerosis: a potential diagnostic biomarker and therapeutic target

《医学前沿（英文）》 2022年 第16卷 第5期   页码 723-735 doi: 10.1007/s11684-021-0905-y

摘要： Amyotrophic lateral sclerosis (ALS) is the most common motor neuron disease. At present, no definite ALS biomarkers are available. In this study, exosomes from the plasma of patients with ALS and healthy controls were extracted, and differentially expressed exosomal proteins were compared. Among them, the expression of exosomal coronin-1a (CORO1A) was 5.3-fold higher than that in the controls. CORO1A increased with disease progression at a certain proportion in the plasma of patients with ALS and in the spinal cord of ALS mice. CORO1A was also overexpressed in NSC-34 motor neuron-like cells, and apoptosis, oxidative stress, and autophagic protein expression were evaluated. CORO1A overexpression resulted in increased apoptosis and oxidative stress, overactivated autophagy, and hindered the formation of autolysosomes. Moreover, CORO1A activated Ca2+-dependent phosphatase calcineurin, thereby blocking the fusion of autophagosomes and lysosomes. The inhibition of calcineurin activation by cyclosporin A reversed the damaged autolysosomes. In conclusion, the role of CORO1A in ALS pathogenesis was discovered, potentially affecting the disease onset and progression by blocking autophagic flux. Therefore, CORO1A might be a potential biomarker and therapeutic target for ALS.

关键词： amyotrophic lateral sclerosis     coronin-1a     autophagy     pathogenesis    

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Review of hand, foot and mouth disease

Lan-Juan LI MD,

《医学前沿（英文）》 2010年 第4卷 第2期   页码 139-146 doi: 10.1007/s11684-010-0033-6

摘要： Hand, foot and mouth disease (HFMD) is an acute viral illness that primarily affects infants and young children, and often occurs in clusters or outbreaks. The major causative agents of HFMD are coxsackievirus A16 (CVA16), human enterovirus 71 (HEV71) and coxsackievirus A10 (CVA10), of the genus in the family Picornaviridae. HFMD caused by EV71 is associated with severe neurological complications and death. Since the late 1990s, several major epidemics of EV71 HFMD have swept through the Asia-Pacific region, associated with a rapid fulminant course, severe neurological complications, and a large number of fatalities. Until now, little has been known about the genetics and transmission trends of the fast-mutation virus, and there is no effective and specific antiviral therapy or vaccine for HFMD. It is time to step up efforts to understand the molecular epidemics and pathogenesis so that we can develop effective management strategies and surveillance programs.

关键词： hand     foot and mouth disease     epidemiology     pathogenesis     management     surveillance    

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关于子宫内膜异位症的再认识及其意义

郎景和

《中国工程科学》 2009年 第11卷 第10期   页码 137-142

摘要：

子宫内膜异位症是严重影响育龄妇女健康及生育的常见病、多发病。课题组在该病的基础与临床研究过程中，形成了独到的病因学观点。即认为，内异症是由异常的子宫在位内膜组织随经血逆流至盆腹腔，在异地完成粘附、侵袭、血管形成之病理过程，而形成病灶。致病的关键系子宫在位内膜本身，而在位内膜干/祖细胞或其微环境的改变可能是根本原因。此外，内异症还表现出类肿瘤特质。上述病因学研究结果推进了临床诊疗技术和水平。近年来在位内膜标志物的检测和局部治疗更反映了“源头”诊疗的新观念。对内异症发病机制的再认识和新观念，直接影响了临床问题解决的新方向。

关键词： 子宫内膜异位症     发病机制     诊断     治疗    

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Pathogenesis of pandemic H1N1 2009 influenza virus infection and the implication on management

Kelvin Kai-Wang TO FRCPath, Iris Wai-Sum LI FRCP, Ivan Fan-Ngai HUNG FRCP, Vincent Chi-Chung CHENG FRCPath, Kwok-Yung YUEN MD,

《医学前沿（英文）》 2010年 第4卷 第2期   页码 147-156 doi: 10.1007/s11684-010-0030-9

摘要： The pandemic H1N1 2009 influenza virus has caused the first influenza pandemic of the 21st century, leading to disproportionate fatalities in the low-risk population despite the generally mild nature of the illness. Advances in sci

关键词： influenza A virus     H1N1 subtype     pandemic     pathogenesis     virulence factors     immunity     management     antiviral    

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Pathogenesis sequences in Gejiu miners with lung cancer: an introduction

null

《医学前沿（英文）》 2015年 第9卷 第3期   页码 344-349 doi: 10.1007/s11684-015-0399-6

摘要：

Tin miners in Gejiu, Yunnan Province, China are at high risk of developing lung cancer with significant occupational characteristics. Tissue samples from these miners presented pathological characteristics, such as fibroplasia in carcinomas, peri-cancerous tissue in lung cancers, and hyperplasia and dysplasia of epithelial cells in peri-cancerous tissue. Carcinomas induced by Yunnan tin mine dust in the animal experiment underwent inflammation, fibroplasia, hyperplasia, dysplasia, and carcinogenesis of epithelial cells. A correlated and synergistic relationship was observed between bronchial epithelial cell transformation and fibroblast activation in vitro induced by mine dust. Fibroblast hyperplasia and activation are important factors that promote the transformation and carcinogenesis of epithelial cells. Our findings suggested that pulmonary fibrosis may increase the risk and promote the occurrence of lung cancer, which can lead to lung fiber hyperplasia.

关键词： Yunnan tin mine     miners     lung cancer    

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标题 作者 时间 类型 操作

Cross-sectional network analysis of plasma proteins/metabolites correlated with pathogenesis and therapeutic

期刊论文

Obesity-related glomerulopathy: pathogenesis, pathologic, clinical characteristics and treatment

null

期刊论文

Epidemiology, pathogenesis, and management of coronavirus disease 2019-associated stroke

期刊论文

Various brain-eating amoebae: the protozoa, the pathogenesis, and the disease

期刊论文

MicroRNAs and lung cancers: from pathogenesis to clinical implications

null

期刊论文

Advances in COVID-19: the virus, the pathogenesis, and evidence-based control and therapeutic strategies

Guangbiao Zhou, Saijuan Chen, Zhu Chen

期刊论文

Molecular pathogenesis of acute myeloid leukemia: A diverse disease with new perspectives

Felicitas THOL, Arnold GANSER

期刊论文

Pathogenesis, diagnosis, and treatment of recurrent spontaneous abortion with immune type

Qi-De LIN, Li-Hua QIU

期刊论文

Toll-like receptor signaling in hematopoietic homeostasis and the pathogenesis of hematologic diseases

null

期刊论文

AML1-ETO driven acute leukemia: insights into pathogenesis and potential therapeutic approaches

null

期刊论文

Increased expression of coronin-1a in amyotrophic lateral sclerosis: a potential diagnostic biomarker and therapeutic target

期刊论文

Review of hand, foot and mouth disease

Lan-Juan LI MD,

期刊论文

关于子宫内膜异位症的再认识及其意义

郎景和

期刊论文

Pathogenesis of pandemic H1N1 2009 influenza virus infection and the implication on management

Kelvin Kai-Wang TO FRCPath, Iris Wai-Sum LI FRCP, Ivan Fan-Ngai HUNG FRCP, Vincent Chi-Chung CHENG FRCPath, Kwok-Yung YUEN MD,

期刊论文

Pathogenesis sequences in Gejiu miners with lung cancer: an introduction

null

期刊论文