Frontiers of Medicine

ISSN 2095-0217

ISSN 2095-0225(Online)

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Single-cell RNA-seq data analysis on the receptor ACE2 expression reveals the potential risk of different human organs vulnerable to 2019-nCoV infection
Xin Zou, Ke Chen, Jiawei Zou, Peiyi Han, Jie Hao, Zeguang Han
Front. Med.    2020, 14 (2): 185-192.   https://doi.org/10.1007/s11684-020-0754-0
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It has been known that, the novel coronavirus, 2019-nCoV, which is considered similar to SARS-CoV, invades human cells via the receptor angiotensin converting enzyme II (ACE2). Moreover, lung cells that have ACE2 expression may be the main target cells during 2019-nCoV infection. However, some patients also exhibit non-respiratory symptoms, such as kidney failure, implying that 2019-nCoV could also invade other organs. To construct a risk map of different human organs, we analyzed the single-cell RNA sequencing (scRNA-seq) datasets derived from major human physiological systems, including the respiratory, cardiovascular, digestive, and urinary systems. Through scRNA-seq data analyses, we identified the organs at risk, such as lung, heart, esophagus, kidney, bladder, and ileum, and located specific cell types (i.e., type II alveolar cells (AT2), myocardial cells, proximal tubule cells of the kidney, ileum and esophagus epithelial cells, and bladder urothelial cells), which are vulnerable to 2019-nCoV infection. Based on the findings, we constructed a risk map indicating the vulnerability of different organs to 2019-nCoV infection. This study may provide potential clues for further investigation of the pathogenesis and route of 2019-nCoV infection.

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Non-invasive continuous blood pressure monitoring: a review of current applications
Elena Chung, Guo Chen, Brenton Alexander, Maxime Cannesson
Front Med    2013, 7 (1): 91-101.   https://doi.org/10.1007/s11684-013-0239-5
Abstract   HTML   PDF (496KB)

Blood pressure monitoring has come a long way from the initial observations made by Reverend Hales in the 18th century. There are none that deny the importance of monitoring perioperative blood pressure; however, the limited ability of the current prevalent technology (oscillometric blood pressure monitoring) to offer continuous blood pressure measurements leaves room for improvement. Invasive monitoring is able to detect beat-to-beat blood pressure measurement, but the risks inherent to the procedure make it unsuitable for routine use except when this risk is outweighed by the benefits. This review focuses on the discoveries which have led up to the current blood pressure monitoring technologies, and especially the creation of those offering non-invasive but continuous blood pressure monitoring capabilities, including their methods of measurement and limitations.

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Cited: Crossref(73) WebOfScience(65)
Diffuse cystic lung diseases
Jay H. Ryu, Xinlun Tian, Misbah Baqir, Kaifeng Xu
Front Med    2013, 7 (3): 316-327.   https://doi.org/10.1007/s11684-013-0269-z
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Diffuse cystic lung diseases are uncommon but can present a diagnostic challenge because increasing number of diseases have been associated with this presentation. Cyst in the lung is defined as a round parenchymal lucency with a well-defined thin wall (<2 mm thickness). Focal or multifocal cystic lesions include blebs, bullae, pneumatoceles, congenital cystic lesions, traumatic lesions, and several infectious processes such as coccidioidomycosis, Pneumocystis jiroveci pneumonia, and hydatid disease. “Diffuse” distribution in the lung implies involvement of all lobes. Diffuse lung involvement with cystic lesions can be seen in pulmonary lymphangioleiomyomatosis, pulmonary Langerhans’ cell histiocytosis, lymphoid interstitial pneumonia, Birt-Hogg-Dubé syndrome, amyloidosis, light chain deposition disease, honeycomb lung associated with advanced fibrosis, and several other rare causes including metastatic disease. High-resolution computed tomography of the chest helps define morphologic features of the lung lesions as well as their distribution and associated features such as intrathoracic lymphadenopathy. Correlating the tempo of the disease process and clinical context with chest imaging findings serve as important clues to defining the underlying nature of the cystic lung disease and guide diagnostic evaluation as well as management.

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Zinc homeostasis in the metabolic syndrome and diabetes
Xiao Miao, Weixia Sun, Yaowen Fu, Lining Miao, Lu Cai
Front Med    2013, 7 (1): 31-52.   https://doi.org/10.1007/s11684-013-0251-9
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Zinc (Zn) is an essential mineral that is required for various cellular functions. Zn dyshomeostasis always is related to certain disorders such as metabolic syndrome, diabetes and diabetic complications. The associations of Zn with metabolic syndrome, diabetes and diabetic complications, thus, stem from the multiple roles of Zn: (1) a constructive component of many important enzymes or proteins, (2) a requirement for insulin storage and secretion, (3) a direct or indirect antioxidant action, and (4) an insulin-like action. However, whether there is a clear cause-and-effect relationship of Zn with metabolic syndrome, diabetes, or diabetic complications remains unclear. In fact, it is known that Zn deficiency is a common phenomenon in diabetic patients. Chronic low intake of Zn was associated with the increased risk of diabetes and diabetes also impairs Zn metabolism. Theoretically Zn supplementation should prevent the metabolic syndrome, diabetes, and diabetic complications; however, limited available data are not always supportive of the above notion. Therefore, this review has tried to summarize these pieces of available information, possible mechanisms by which Zn prevents the metabolic syndrome, diabetes, and diabetic complications. In the final part, what are the current issues for Zn supplementation were also discussed.

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Leptin signaling and leptin resistance
Yingjiang Zhou, Liangyou Rui
Front Med    2013, 7 (2): 207-222.   https://doi.org/10.1007/s11684-013-0263-5
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Leptin is secreted into the bloodstream by adipocytes and is required for the maintenance of energy homeostasis and body weight. Leptin deficiency or genetic defects in the components of the leptin signaling pathways cause obesity. Leptin controls energy balance and body weight mainly through leptin receptor b (LEPRb)-expressing neurons in the brain, particularly in the hypothalamus. These LEPRb-expressing neurons function as the first-order neurons that project to the second-order neurons located within and outside the hypothalamus, forming a neural network that controls the energy homeostasis and body weight. Multiple factors, including inflammation and endoplasmic reticulum (ER) stress, contribute to leptin resistance. Leptin resistance is the key risk factor for obesity. This review is focused on recent advance about leptin action, leptin signaling, and leptin resistance.

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Cited: Crossref(139) WebOfScience(138)
Talin and kindlin: the one-two punch in integrin activation
Feng Ye, Adam K. Snider, Mark H. Ginsberg
Front Med    2014, 8 (1): 6-16.   https://doi.org/10.1007/s11684-014-0317-3
Abstract   HTML   PDF (333KB)

Proper cell-cell and cell-matrix contacts mediated by integrin adhesion receptors are important for development, immune response, hemostasis and wound healing. Integrins pass trans-membrane signals bidirectionally through their regulated affinities for extracellular ligands and intracellular signaling molecules. Such bidirectional signaling by integrins is enabled by the conformational changes that are often linked among extracellular, transmembrane and cytoplasmic domains. Here, we review how talin-integrin and kindlin-integrin interactions, in cooperation with talin-lipid and kindlin-lipid interactions, regulate integrin affinities and how the progress in these areas helps us understand integrin-related diseases.

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Medical applications of phytoestrogens from the Thai herb Pueraria mirifica
Suchinda Malaivijitnond
Front Med    2012, 6 (1): 8-21.   https://doi.org/10.1007/s11684-012-0184-8
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Pueraria mirifica Airy Shaw et Suvatabandhu is a medicinal plant endemic to Thailand. It has been used in Thai folklore medicine for its rejuvenating qualities in aged women and men for nearly one hundred years. Indeed, it has been claimed that P. mirifica contains active phytoestrogens (plant substances with estrogen-like activity). Using high performance liquid chromatography, at least 17 phytoestrogens, mainly isoflavones, have been isolated. Thus, fairly considerable scientific researches, both in vitro in cell lines and in vivo in various species of animals including humans, have been conducted to date to address its estrogenic activity on the reproductive organs, bones, cardiovascular diseases and other climacteric related symptoms. The antioxidative capacity and antiproliferative effect on tumor cell lines have also been assessed. In general, P. mirifica could be applicable for preventing, or as a therapeutic for, the symptoms related to estrogen deficiency in menopausal women as well as in andropausal men. However, the optimal doses for each desirable effect and the balance to avoid undesired side effects need to be calculated before use.

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Systematic review for geo-authentic Lonicerae Japonicae Flos
Xingyue Yang, Yali Liu, Aijuan Hou, Yang Yang, Xin Tian, Liyun He
Front. Med.    2017, 11 (2): 203-213.   https://doi.org/10.1007/s11684-017-0504-0
Abstract   HTML   PDF (181KB)

In traditional Chinese medicine, Lonicerae Japonicae Flos is commonly used as anti-inflammatory, antiviral, and antipyretic herbal medicine, and geo-authentic herbs are believed to present the highest quality among all samples from different regions. To discuss the current situation and trend of geo-authentic Lonicerae Japonicae Flos, we searched Chinese Biomedicine Literature Database, Chinese Journal Full-text Database, Chinese Scientific Journal Full-text Database, Cochrane Central Register of Controlled Trials, Wanfang, and PubMed. We investigated all studies up to November 2015 pertaining to quality assessment, discrimination, pharmacological effects, planting or processing, or ecological system of geo-authentic Lonicerae Japonicae Flos. Sixty-five studies mainly discussing about chemical fingerprint, component analysis, planting and processing, discrimination between varieties, ecological system, pharmacological effects, and safety were systematically reviewed. By analyzing these studies, we found that the key points of geo-authentic Lonicerae Japonicae Flos research were quality and application. Further studies should focus on improving the quality by selecting the more superior of all varieties and evaluating clinical effectiveness.

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Histone variants: critical determinants in tumour heterogeneity
Tao Wang, Florent Chuffart, Ekaterina Bourova-Flin, Jin Wang, Jianqing Mi, Sophie Rousseaux, Saadi Khochbin
Front. Med.    2019, 13 (3): 289-297.   https://doi.org/10.1007/s11684-018-0667-3
Abstract   HTML   PDF (945KB)

Malignant cell transformation could be considered as a series of cell reprogramming events driven by oncogenic transcription factors and upstream signalling pathways. Chromatin plasticity and dynamics are critical determinants in the control of cell reprograming. An increase in chromatin dynamics could therefore constitute an essential step in driving oncogenesis and in generating tumour cell heterogeneity, which is indispensable for the selection of aggressive properties, including the ability of cells to disseminate and acquire resistance to treatments. Histone supply and dosage, as well as histone variants, are the best-known regulators of chromatin dynamics. By facilitating cell reprogramming, histone under-dosage and histone variants should also be crucial in cell transformation and tumour metastasis. Here we summarize and discuss our knowledge of the role of histone supply and histone variants in chromatin dynamics and their ability to enhance oncogenic cell reprogramming and tumour heterogeneity.

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Advances in immunopathogenesis of adult immune thrombocytopenia
Xinguang Liu, Yu Hou, Jun Peng
Front Med    2013, 7 (4): 418-424.   https://doi.org/10.1007/s11684-013-0297-8
Abstract   HTML   PDF (207KB)

Primary immune thrombocytopenia (ITP) is an autoimmune disorder characterized by immune-mediated accelerated platelet destruction and/or suppressed platelet production. Although the development of autoantibodies against platelet glycoproteins remains central in the pathophysiology of ITP, several abnormalities involving the cellular mechanisms of immune modulation have been identified, and the pathways behind the immune-mediated destruction of platelets have opened new avenues for the design of specific immunotherapies in an attempt to reduce the platelet destruction. This review is primarily focused on the recent literature with respect to immunopathological mechanisms in patients with ITP.

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Insulin resistance and the metabolism of branched-chain amino acids
Jingyi Lu, Guoxiang Xie, Weiping Jia, Wei Jia
Front Med    2013, 7 (1): 53-59.   https://doi.org/10.1007/s11684-013-0255-5
Abstract   HTML   PDF (196KB)

Insulin resistance (IR) is a key pathological feature of metabolic syndrome and subsequently causes serious health problems with an increased risk of several common metabolic disorders. IR related metabolic disturbance is not restricted to carbohydrates but impacts global metabolic network. Branched-chain amino acids (BCAAs), namely valine, leucine and isoleucine, are among the nine essential amino acids, accounting for 35% of the essential amino acids in muscle proteins and 40% of the preformed amino acids required by mammals. The BCAAs are particularly responsive to the inhibitory insulin action on amino acid release by skeletal muscle and their metabolism is profoundly altered in insulin resistant conditions and/or insulin deficiency. Although increased circulating BCAA concentration in insulin resistant conditions has been noted for many years and BCAAs have been reported to be involved in the regulation of glucose homeostasis and body weight, it is only recently that BCAAs are found to be closely associated with IR. This review will focus on the recent findings on BCAAs from both epidemic and mechanistic studies.

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Epidemiology of fungal infections in China
Min Chen, Yuan Xu, Nan Hong, Yali Yang, Wenzhi Lei, Lin Du, Jingjun Zhao, Xia Lei, Lin Xiong, Langqi Cai, Hui Xu, Weihua Pan, Wanqing Liao
Front. Med.    2018, 12 (1): 58-75.   https://doi.org/10.1007/s11684-017-0601-0
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With the increasing number of immunocompromised hosts, the epidemiological characteristics of fungal infections have undergone enormous changes worldwide, including in China. In this paper, we reviewed the existing data on mycosis across China to summarize available epidemiological profiles. We found that the general incidence of superficial fungal infections in China has been stable, but the incidence of tinea capitis has decreased and the transmission route has changed. By contrast, the overall incidence of invasive fungal infections has continued to rise. The occurrence of candidemia caused by Candida species other than C. albicans and including some uncommon Candida species has increased recently in China. Infections caused by Aspergillus have also propagated in recent years, particularly with the emergence of azole-resistant Aspergillus fumigatus. An increasing trend of cryptococcosis has been noted in China, with Cryptococcus neoformans var. grubii ST 5 genotype isolates as the predominant pathogen. Retrospective studies have suggested that the epidemiological characteristics of Pneumocystis pneumonia in China may be similar to those in other developing countries. Endemic fungal infections, such as sporotrichosis in Northeastern China, must arouse research, diagnostic, and treatment vigilance. Currently, the epidemiological data on mycosis in China are variable and fragmentary. Thus, a nationwide epidemiological research on fungal infections in China is an important need for improving the country’s health.

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Biosynthetic pathway of terpenoid indole alkaloids in Catharanthus roseus
Xiaoxuan Zhu,Xinyi Zeng,Chao Sun,Shilin Chen
Front. Med.    2014, 8 (3): 285-293.   https://doi.org/10.1007/s11684-014-0350-2
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Catharanthus roseus is one of the most extensively investigated medicinal plants, which can produce more than 130 alkaloids, including the powerful antitumor drugs vinblastine and vincristine. Here we review the recent advances in the biosynthetic pathway of terpenoid indole alkaloids (TIAs) in C. roseus, and the identification and characterization of the corresponding enzymes involved in this pathway. Strictosidine is the central intermediate in the biosynthesis of different TIAs, which is formed by the condensation of secologanin and tryptamine. Secologanin is derived from terpenoid (isoprenoid) biosynthetic pathway, while tryptamine is derived from indole biosynthetic pathway. Then various specific end products are produced by different routes during downstream process. Although many genes and corresponding enzymes have been characterized in this pathway, our knowledge on the whole TIA biosynthetic pathway still remains largely unknown up to date. Full elucidation of TIA biosynthetic pathway is an important prerequisite to understand the regulation of the TIA biosynthesis in the medicinal plant and to produce valuable TIAs by synthetic biological technology.

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Mechanisms of insulin resistance in obesity
Jianping Ye
Front Med    2013, 7 (1): 14-24.   https://doi.org/10.1007/s11684-013-0262-6
Abstract   HTML   PDF (195KB)

Obesity increases the risk for type 2 diabetes through induction of insulin resistance. Treatment of type 2 diabetes has been limited by little translational knowledge of insulin resistance although there have been several well-documented hypotheses for insulin resistance. In those hypotheses, inflammation, mitochondrial dysfunction, hyperinsulinemia and lipotoxicity have been the major concepts and have received a lot of attention. Oxidative stress, endoplasmic reticulum (ER) stress, genetic background, aging, fatty liver, hypoxia and lipodystrophy are active subjects in the study of these concepts. However, none of those concepts or views has led to an effective therapy for type 2 diabetes. The reason is that, there has been no consensus for a unifying mechanism of insulin resistance. In this review article, literature is critically analyzed and reinterpreted for a new energy-based concept of insulin resistance, in which insulin resistance is a result of energy surplus in cells. The energy surplus signal is mediated by ATP and sensed by adenosine monophosphate-activated protein kinase (AMPK) signaling pathway. Decreasing ATP level by suppression of production or stimulation of utilization is a promising approach in the treatment of insulin resistance. In support, many of existing insulin sensitizing medicines inhibit ATP production in mitochondria. The effective therapies such as weight loss, exercise, and caloric restriction all reduce ATP in insulin sensitive cells. This new concept provides a unifying cellular and molecular mechanism of insulin resistance in obesity, which may apply to insulin resistance in aging and lipodystrophy.

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Epigenetic dysregulation in hepatocellular carcinoma: focus on polycomb group proteins
Sandy Leung-Kuen Au, Irene Oi-Lin Ng, Chun-Ming Wong
Front Med    2013, 7 (2): 231-241.   https://doi.org/10.1007/s11684-013-0253-7
Abstract   HTML   PDF (319KB)

Hepatocellular carcinoma (HCC) development is characterized by the presence of epigenetic alterations, including promoter DNA hypermethylation and post-translational modifications of histone, which profoundly affect expression of a wide repertoire of genes critical for cancer development. Emerging data suggest that deregulation of polycomb group (PcG) proteins, which are key chromatin modifiers repressing gene transcription during developmental stage, plays a causative role in oncogenesis. PcG proteins assemble into polycomb repressive complex 1 (PRC1) and polycomb repressive complex 2 (PRC2) to impose the histone H3 lysine 27 trimethylation (H3K27me3) modification for repression. In this review, we will first recapitulate the mechanisms of two key epigenetic pathways: DNA methylation and histone modifications. Specifically, we will focus our discussion on the molecular roles of PcG proteins. Next, we will highlight recent findings on PcG proteins, their clinicopathological implication and their downstream molecular consequence in hepatocarcinogenesis. Last but not least, we will consider the therapeutic potential of targeting enhancer of zeste homolog 2 (EZH2) as a possible treatment for HCC. Improving our understanding on the roles of PcG proteins in hepatocarcinogenesis can benefit the development of epigenetic-based therapy.

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Triterpenoid inducers of Nrf2 signaling as potential therapeutic agents in sickle cell disease: a review
Amma Owusu-Ansah,Sung Hee Choi,Agne Petrosiute,John J. Letterio,Alex Yee-Chen Huang
Front. Med.    2015, 9 (1): 46-56.   https://doi.org/10.1007/s11684-015-0375-1
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Sickle cell disease (SCD) is an inherited disorder of hemoglobin in which the abnormal hemoglobin S polymerizes when deoxygenated. This polymerization of hemoglobin S not only results in hemolysis and vaso-occlusion but also precipitates inflammation, oxidative stress and chronic organ dysfunction. Oxidative stress is increasingly recognized as an important intermediate in these pathophysiological processes and is therefore an important target for therapeutic intervention. The transcription factor nuclear erythroid derived- 2 related factor 2 (Nrf2) controls the expression of anti-oxidant enzymes and is emerging as a protein whose function can be exploited with therapeutic intent. This review article is focused on triterpenoids that activate Nrf2, and their potential for reducing oxidative stress in SCD as an approach to prevent organ dysfunction associated with this disease. A brief overview of oxidative stress in the clinical context of SCD is accompanied by a discussion of several pathophysiological mechanisms contributing to oxidative stress. Finally, these mechanisms are then related to current management strategies in SCD that are either utilized currently or under evaluation. The article concludes with a perspective on the potential of the various therapeutic interventions to reduce oxidative stress and morbidity associated with SCD.

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A case of thymic Langerhans cell histiocytosis with diabetes insipidus as the first presentation
Xiaoyan Chen, Xiaochun Huang, Yuan Qiu, Hanzhang Chen, Yingyu Fu, Xinchun Li
Front Med    2013, 7 (1): 143-146.   https://doi.org/10.1007/s11684-013-0238-6
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Langerhans cell histiocytosis (LCH) is an idiopathic group of reactive proliferative diseases linked to aberrant immunity, pathologically characterized by clonal proliferation of Langerhans cells. LCH rarely involves the thymus. We report a case of thymic LCH with diabetes insipidus as the first presentation, without evidence of myasthenia gravis and without evidenced involvement of the skin, liver, spleen, bones, lungs and superficial lymph nodes. This present case may have important clinical implications. In screening for LCH lesions, attention should be attached to rarely involved sites in addition to commonly involved organs. Follow-up and imageological examination are very important to a final diagnosis.

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CRISPR-Cas9 mediated LAG-3 disruption in CAR-T cells
Yongping Zhang, Xingying Zhang, Chen Cheng, Wei Mu, Xiaojuan Liu, Na Li, Xiaofei Wei, Xiang Liu, Changqing Xia, Haoyi Wang
Front. Med.    2017, 11 (4): 554-562.   https://doi.org/10.1007/s11684-017-0543-6
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T cells engineered with chimeric antigen receptor (CAR) have been successfully applied to treat advanced refractory B cell malignancy. However, many challenges remain in extending its application toward the treatment of solid tumors. The immunosuppressive nature of tumor microenvironment is considered one of the key factors limiting CAR-T efficacy. One negative regulator of T cell activity is lymphocyte activation gene-3 (LAG-3). We successfully generated LAG-3 knockout T and CAR-T cells with high efficiency using CRISPR-Cas9 mediated gene editing and found that the viability and immune phenotype were not dramatically changed during in vitro culture. LAG-3 knockout CAR-T cells displayed robust antigen-specific antitumor activity in cell culture and in murine xenograft model, which is comparable to standard CAR-T cells. Our study demonstrates an efficient approach to silence immune checkpoint in CAR-T cells via gene editing.

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A new minimally invasive treatment for anal fistula
Rui Zhu,Lin Shen,Caoyuan Wang,Yanping Yang,Rui Chen,Hen Fang,Xiaojuan Xu
Front. Med.    2015, 9 (1): 77-81.   https://doi.org/10.1007/s11684-014-0352-0
Abstract   HTML   PDF (708KB)

In colorectal surgery, eradicating the fistula and maintaining continence are still complex challenges for a colorectal surgeon. A minimally invasive method using a novel device was performed to consecutively treat 14 patients with anal fistula from August 2008 to November 2009. After a follow-up period of 36 months, 13 patients achieved successful closure of their fistula tracts, and recurrence occurred only in one patient. Recurrence was due to the delay of dressing change. No patient had interference with continence, and no major intra- and post-operative complications were identified. Using the novel device with invasive methods can be a promising alternative for managing anal fistulas.

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Molecular mechanisms of fatty liver in obesity
Lixia Gan,Wei Xiang,Bin Xie,Liqing Yu
Front. Med.    2015, 9 (3): 275-287.   https://doi.org/10.1007/s11684-015-0410-2
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Nonalcoholic fatty liver disease (NAFLD) covers a spectrum of liver disorders ranging from simple steatosis to advanced pathologies, including nonalcoholic steatohepatitis and cirrhosis. NAFLD significantly contributes to morbidity and mortality in developed societies. Insulin resistance associated with central obesity is the major cause of hepatic steatosis, which is characterized by excessive accumulation of triglyceride-rich lipid droplets in the liver. Accumulating evidence supports that dysregulation of adipose lipolysis and liver de novo lipogenesis (DNL) plays a key role in driving hepatic steatosis. In this work, we reviewed the molecular mechanisms responsible for enhanced adipose lipolysis and increased hepatic DNL that lead to hepatic lipid accumulation in the context of obesity. Delineation of these mechanisms holds promise for developing novel avenues against NAFLD.

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Landscape of emerging and re-emerging infectious diseases in China: impact of ecology, climate, and behavior
Qiyong Liu, Wenbo Xu, Shan Lu, Jiafu Jiang, Jieping Zhou, Zhujun Shao, Xiaobo Liu, Lei Xu, Yanwen Xiong, Han Zheng, Sun Jin, Hai Jiang, Wuchun Cao, Jianguo Xu
Front. Med.    2018, 12 (1): 3-22.   https://doi.org/10.1007/s11684-017-0605-9
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For the past several decades, the infectious disease profile in China has been shifting with rapid developments in social and economic aspects, environment, quality of food, water, housing, and public health infrastructure. Notably, 5 notifiable infectious diseases have been almost eradicated, and the incidence of 18 additional notifiable infectious diseases has been significantly reduced. Unexpectedly, the incidence of over 10 notifiable infectious diseases, including HIV, brucellosis, syphilis, and dengue fever, has been increasing. Nevertheless, frequent infectious disease outbreaks/events have been reported almost every year, and imported infectious diseases have increased since 2015. New pathogens and over 100 new genotypes or serotypes of known pathogens have been identified. Some infectious diseases seem to be exacerbated by various factors, including rapid urbanization, large numbers of migrant workers, changes in climate, ecology, and policies, such as returning farmland to forests. This review summarizes the current experiences and lessons from China in managing emerging and re-emerging infectious diseases, especially the effects of ecology, climate, and behavior, which should have merits in helping other countries to control and prevent infectious diseases.

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Mechanisms of resistance to third-generation EGFR tyrosine kinase inhibitors
Shuhang Wang,Yongping Song,Feifei Yan,Delong Liu
Front. Med.    2016, 10 (4): 383-388.   https://doi.org/10.1007/s11684-016-0488-1
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The tyrosine kinase inhibitors (TKI) of the epidermal growth factor receptor (EGFR) are becoming the first line of therapy for advanced non-small cell lung cancer (NSCLC). Acquired mutations in EGFR account for one of the major mechanisms of resistance to the TKIs. Three generations of EGFR TKIs have been used in clinical applications. AZD9291 (osimertinib; Tagrisso) is the first and only FDA approved third-generation EGFR TKI for T790M-positive advanced NSCLC patients. However, resistance to AZD9291 arises after 9–13 months of therapy. The mechanisms of resistance to third-generation inhibitors reported to date include the EGFR C797S mutation, EGFR L718Q mutation, and amplifications of HER-2, MET, or ERBB2. To overcome the acquired resistance to AZD9291, EAI045 was discovered and recently reported to be an allosteric EGFR inhibitor that overcomes T790M- and C797S-mediated resistance. This review summarizes recent investigations on the mechanisms of resistance to the EGFR TKIs, as well as the latest development of EAI045 as a fourth-generation EGFR inhibitor.

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FGF23 associated bone diseases
Eryuan Liao
Front Med    2013, 7 (1): 65-80.   https://doi.org/10.1007/s11684-013-0254-6
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Recently, fibroblast growth factor 23 (FGF23) has sparked widespread interest because of its potential role in regulating phosphate and vitamin D metabolism. In this review, we summarized the FGF superfamily, the mechanism of FGF23 on phosphate and vitamin D metabolism, and the FGF23 related bone disease.

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Chronic hepatitis B virus infection: epidemiology, prevention, and treatment in China
Rui Yu,Rong Fan,Jinlin Hou
Front. Med.    2014, 8 (2): 135-144.   https://doi.org/10.1007/s11684-014-0331-5
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Chronic hepatitis B is a major health problem in China. The universal vaccination program since 1992 has changed the epidemiology of hepatitis B virus infection in China from highly to moderately endemic. The most prevalent hepatitis B virus strains in China are genotypes B and C, whereas those in western provinces are genotypes D and C/D hybrid. Chronic hepatitis B poses a heavy burden to the society in China. Different treatment strategies have been explored to improve patient outcomes in a cost-effective manner. However, antiviral drugs with a low genetic barrier to resistance are still extensively used because of the generally low income and limited resources in China. Individualized antiviral therapy is closely associated with translational medicine, which utilizes information from studies on genomics, immune biomarkers, and fibrosis. The results of these studies are crucial in further improving treatment outcomes.

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Fibrous dysplasia involving the calvarium in children?
Chunquan CAI, Qian LI, Qingjiang ZHANG, Changhong SHEN
Front Med Chin    2009, 3 (2): 211-215.   https://doi.org/10.1007/s11684-009-0024-7
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To gain a broader appreciation of the clinical presentation, operative treatment, and outcome of fibrous dysplasia involving the calvarium in children, we retrospectively reviewed a series of cases of fibrous dysplasia involving the calvarium (4 males and 2 females) with patients’ age ranging from 5 to 12 years old. The clinical manifestation, radiographic findings, surgical treatment, outcome and follow-up were evaluated on the basis of medical records. Fibrous dysplasia in the series was monostotic, involving frontal bone (2 cases), temporal bone (1 case), parietal bone (2 cases) and occipital bone (1 case). The patients most commonly presented with enlarging mass and cosmetic complaints. The treatment given, depending on clinical presentation, was simple biopsy with conservative follow-up (2 cases) to cranial resection (4 cases). All the cases were histopathologically confirmed as fibrous dysplasia. It was demonstrated thatfibrous dysplasia involving the calvarium is a typically benign but slowly progressive disorder of bone. Modern imaging modalities and histopathologic analysis have made diagnosis relatively straightforward. Surgery should be reserved for patients with functional impairment or cosmetic deformity. Because of the benign nature of the condition, the surgery itself should be contemplated with great caution in children.

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Middle East respiratory syndrome coronavirus: a comprehensive review
Mahmoud M. Shehata,Mokhtar R. Gomaa,Mohamed A. Ali,Ghazi Kayali
Front. Med.    2016, 10 (2): 120-136.   https://doi.org/10.1007/s11684-016-0430-6
Abstract   HTML   PDF (532KB)

The Middle East respiratory syndrome coronavirus was first identified in 2012 and has since then remained uncontrolled. Cases have been mostly reported in the Middle East, however travel-associated cases and outbreaks have also occurred. Nosocomial and zoonotic transmission of the virus appear to be the most important routes. The infection is severe and highly fatal thus necessitating rapid and efficacious interventions. Here, we performed a comprehensive review of published literature and summarized the epidemiology of the virus. In addition, we summarized the virological aspects of the infection and reviewed the animal models used as well as vaccination and antiviral tested against it.

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Role of Wnt and Notch signaling in regulating hair cell regeneration in the cochlea
Muhammad Waqas,Shasha Zhang,Zuhong He,Mingliang Tang,Renjie Chai
Front. Med.    2016, 10 (3): 237-249.   https://doi.org/10.1007/s11684-016-0464-9
Abstract   HTML   PDF (400KB)

Sensory hair cells in the inner ear are responsible for sound recognition. Damage to hair cells in adult mammals causes permanent hearing impairment because these cells cannot regenerate. By contrast, newborn mammals possess limited regenerative capacity because of the active participation of various signaling pathways, including Wnt and Notch signaling. The Wnt and Notch pathways are highly sophisticated and conserved signaling pathways that control multiple cellular events necessary for the formation of sensory hair cells. Both signaling pathways allow resident supporting cells to regenerate hair cells in the neonatal cochlea. In this regard, Wnt and Notch signaling has gained increased research attention in hair cell regeneration. This review presents the current understanding of the Wnt and Notch signaling pathways in the auditory portion of the inner ear and discusses the possibilities of controlling these pathways with the hair cell fate determiner Atoh1 to regulate hair cell regeneration in the mammalian cochlea.

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Transforming bacterial disease surveillance and investigation using whole-genome sequence to probe the trace
Biao Kan, Haijian Zhou, Pengcheng Du, Wen Zhang, Xin Lu, Tian Qin, Jianguo Xu
Front. Med.    2018, 12 (1): 23-33.   https://doi.org/10.1007/s11684-017-0607-7
Abstract   HTML   PDF (348KB)

Two decades have passed since the first bacterial whole-genome sequencing, which provides new opportunity for microbial genome. Consequently, considerable genetic diversity encoded by bacterial genomes and among the strains in the same species has been revealed. In recent years, genome sequencing techniques and bioinformatics have developed rapidly, which has resulted in transformation and expedited the application of strategy and methodology for bacterial genome comparison used in dissection of infectious disease epidemics. Bacterial whole-genome sequencing and bioinformatic computing allow genotyping to satisfy the requirements of epidemiological study in disease control. In this review, we outline the significance and summarize the roles of bacterial genome sequencing in the context of bacterial disease control and prevention. We discuss the applications of bacterial genome sequencing in outbreak detection, source tracing, transmission mode discovery, and new epidemic clone identification. Wide applications of genome sequencing and data sharing in infectious disease surveillance networks will considerably promote outbreak detection and early warning to prevent the dissemination of bacterial diseases.

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Progress on the research and development of human enterovirus 71 (EV71) vaccines
Zhenglun Liang, Qunying Mao, Fan Gao, Junzhi Wang
Front Med    2013, 7 (1): 111-121.   https://doi.org/10.1007/s11684-012-0237-z
Abstract   HTML   PDF (219KB)

Enterovirus 71 (EV71) infections, which can cause severe complications, have become one of the serious public health issues in the Western Pacific region and China. To date, a number of pharmaceutical companies and institutes have initiated the research and development of EV71 vaccines as a countermeasure. As is the case with innovative vaccine development, there are several critical bottlenecks in EV71 vaccine development that must be overcome before the clinical trials, including the selection of vaccine strain, standardization of the procedure for quantifying neutralizing antibody (NTAb) and antigen, establishment and application of a reference standard and biological standards, development of animal models for the evaluation of protective efficacy, and identification of the target patient population. To tackle these technical obstacles, researchers in Mainland of China have conducted a series of studies concerning the screening of vaccine strains and the establishment of criteria, biological standards and detection methods, thereby advancing EV71 vaccine development. This review summarizes recent worldwide progress on the quality control and evaluation of EV71 vaccines.

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Therapeutic application of hydrogen sulfide donors: the potential and challenges
Dan Wu,Qingxun Hu,Yizhun Zhu
Front. Med.    2016, 10 (1): 18-27.   https://doi.org/10.1007/s11684-015-0427-6
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Hydrogen sulfide (H2S), a colorless gas smelling of rotten egg, has long been considered a toxic gas and environment hazard. However, evidences show that H2S plays a great role in many physiological and pathological activities, and it exhibits different effects when applied at various doses. In this review, we summarize the chemistry and biomedical applications of H2S-releasing compounds, including inorganic salts, phosphorodithioate derivatives, derivatives of Allium sativum extracts, derivatives of thioaminoacids, and derivatives of anti-inflammatory drugs.

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