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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
Abstract   HTML   PDF (1610KB)

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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Cited: Crossref(377) WebOfScience(365)
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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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
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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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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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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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Association of novel mutations and heplotypes in the preS region of hepatitis B virus with hepatocellular carcinoma
Jia-Xin XIE, Jian-Hua YIN, Qi ZHANG, Rui PU, Wen-Ying LU, Hong-Wei ZHANG, Guang-Wen CAO, Jun ZHAO, Hong-Yang WANG,
Front. Med..  2010, 4 (4): 419-429.   https://doi.org/10.1007/s11684-010-0160-0
Abstract   PDF (139KB)
The association of viral mutations and haplotypic carriages with mutations in the preS region of hepatitis B virus (HBV) genotypes B and C with hepatocellular carcinoma (HCC) is of great significance for the prediction of this malignancy, but it remains obscure. We analyzed the preS sequences of HBV genotypes B and C from 1172 HBV-infected subjects including 231 patients with HCC. As compared with the HBV-infected subjects without HCC, C2875T, G2946C, A3054C, C3060A, T3066C, C3116T, A3120C, G3191A, A1C, C7A, C10A, A31C, C76T, G105C, and G147C in both genotypes were significantly associated with increased risks of HCC. C2875A, G2950A, G2951A, A3054T, C3060T, T3066A, T3069G, A3120T, and G3191C were significantly associated with increased risks of HCC in genotype C, whereas these mutations were inversely associated with HCC in genotype B. Multivariate regression analyses showed that C76A/T was a novel factor independently associated with an increased risk of HCC, as compared with those without HCC. The frequencies of haplotypes 2964A-3116T-preS2 start codon wild-type-7C, 2964C-3116T-7A-76C, and 2964A-3116T-7C-76A/T were significantly higher in the patients with HCC (P<0.001), whereas a haplotypic carriage with a single mutation and another three wild-types were inversely associated with HCC. Conclusively, the association of HBV mutations in the preS region with HCC depends on HBV genotype and haplotypic carriage with two or more mutations that are each associated with an increased risk of HCC independently.
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Top-geoherbs of traditional Chinese medicine: common trait, quality characteristics and formation
Luqi Huang, Lanping Guo, Chaoyi Ma, Wei Gao, Qingjun Yuan
Front Med.  2011, 5 (2): 185-194.   https://doi.org/10.1007/s11684-011-0141-y
Abstract   HTML   PDF (306KB)

Top-geoherbs used in China are always featured with high qualities, and they grow in specified areas with specific environment. Recently, researches on top-geoherbs have attracted increasing attention in China and other countries. In order to have a thorough knowledge of top-geoherbs, this article reviews the concept, historical evolution, common trait and quality characteristics of top-geoherbs, and explains the forming mechanism including genetic mechanism and environmental mechanism. In addition, it introduces the influence of human factors on the quality of top-geoherbs. Finally, it proposes some problems that should be paid attention to in the researches on top-geoherbs.

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Clinical study using mesenchymal stem cells for the treatment of patients with severe COVID-19
Lingling Tang, Yingan Jiang, Mengfei Zhu, Lijun Chen, Xiaoyang Zhou, Chenliang Zhou, Peng Ye, Xiaobei Chen, Baohong Wang, Zhenyu Xu, Qiang Zhang, Xiaowei Xu, Hainv Gao, Xiaojun Wu, Dong Li, Wanli Jiang, Jingjing Qu, Charlie Xiang, Lanjuan Li
Front. Med..  2020, 14 (5): 664-673.   https://doi.org/10.1007/s11684-020-0810-9
Abstract   HTML   PDF (301KB)

The coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 was identified in December 2019. The symptoms include fever, cough, dyspnea, early symptom of sputum, and acute respiratory distress syndrome (ARDS). Mesenchymal stem cell (MSC) therapy is the immediate treatment used for patients with severe cases of COVID-19. Herein, we describe two confirmed cases of COVID-19 in Wuhan to explore the role of MSC in the treatment of COVID-19. MSC transplantation increases the immune indicators (including CD4 and lymphocytes) and decreases the inflammation indicators (interleukin-6 and C-reactive protein). High-flow nasal cannula can be used as an initial support strategy for patients with ARDS. With MSC transplantation, the fraction of inspired O2 (FiO2) of the two patients gradually decreased while the oxygen saturation (SaO2) and partial pressure of oxygen (PO2) improved. Additionally, the patients’ chest computed tomography showed that bilateral lung exudate lesions were adsorbed after MSC infusion. Results indicated that MSC transplantation provides clinical data on the treatment of COVID-19 and may serve as an alternative method for treating COVID-19, particularly in patients with ARDS.

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Behavioral methods for the functional assessment of hair cells in zebrafish
Qin Yang, Peng Sun, Shi Chen, Hongzhe Li, Fangyi Chen
Front. Med..  2017, 11 (2): 178-190.   https://doi.org/10.1007/s11684-017-0507-x
Abstract   HTML   PDF (338KB)

Zebrafish is an emerging animal model for studies on auditory system. This model presents high comparability with humans, good accessibility to the hearing organ, and high throughput capacity. To better utilize this animal model, methodologies need to be used to quantify the hearing function of the zebrafish. Zebrafish displays a series of innate and robust behavior related to its auditory function. Here, we reviewed the advantage of using zebrafish in auditory research and then introduced three behavioral tests, as follows: the startle response, the vestibular-ocular reflex, and rheotaxis. These tests are discussed in terms of their physiological characteristics, up-to-date technical development, and apparatus description. Test limitation and areas to improve are also introduced. Finally, we revealed the feasibility of these applications in zebrafish behavioral assessment and their potential in the high-throughput screening on hearing-related genes and drugs.

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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
Abstract   HTML   PDF (423KB)

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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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
Abstract   HTML   PDF (776KB)

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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Metabolomics in human type 2 diabetes research
Jingyi Lu, Guoxiang Xie, Weiping Jia, Wei Jia
Front Med.  2013, 7 (1): 4-13.   https://doi.org/10.1007/s11684-013-0248-4
Abstract   HTML   PDF (181KB)

The high prevalence of diabetes and diabetic complications has caused a huge burden on the modern society. Although scientific advances have led to effective strategies for preventing and treating diabetes over the past several decades, little progress has been made toward curing the disease or even getting it under control, from a public health and overall societal standpoint. There is still a lack of reliable biomarkers indicative of metabolic alterations associated with diabetes and different drug responses, highlighting the need for the development of early diagnostic and prognostic markers for diabetes and diabetic complications. The emergence of metabolomics has allowed researchers to systemically measure the small molecule metabolites, which are sensitive to the changes of both environmental and genetic factors and therefore, could be regarded as the link between genotypes and phenotypes. During the last decade, the progression made in metabolomics has provided insightful information on disease development and disease onset prediction. Recent studies using metabolomics approach coupled with statistical tools to predict incident diabetes revealed a number of metabolites that are significantly altered, including branched-chain and aromatic amino acids, such as isoleucine, leucine, valine, tyrosine and phenylalanine, as diagnostic or highly-significant predictors of future diabetes. This review summarizes the current findings of metabolomic studies in human investigations with the most common form of diabetes, type 2 diabetes.

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Middle East respiratory syndrome coronavirus in pediatrics: a report of seven cases from Saudi Arabia
Sarah H. Alfaraj, Jaffar A. Al-Tawfiq, Talal A. Altuwaijri, Ziad A. Memish
Front. Med..  2019, 13 (1): 126-130.   https://doi.org/10.1007/s11684-017-0603-y
Abstract   HTML   PDF (189KB)

Infection with Middle East respiratory syndrome coronavirus (MERS-CoV) emerged in 2012 as an important respiratory disease with high fatality rates of 40%–60%. Despite the increased number of cases over subsequent years, the number of pediatric cases remained low. A review of studies conducted from June 2012 to April 19, 2016 reported 31 pediatric MERS-CoV cases. In this paper, we present the clinical and laboratory features of seven patients with pediatric MERS. Five patients had no underlying medical illnesses, and three patients were asymptomatic. Of the seven cases, four (57%) patients sought medical advice within 1–7 days from the onset of symptoms. The three other patients (43%) were asymptomatic and were in contact with patients with confirmed diagnosis of MERS-CoV. The most common presenting symptoms were fever (57%), cough (14%), shortness of breath (14%), vomiting (28%), and diarrhea (28%). Two (28.6%) patients had platelet counts of<150 × 109/L, and one patient had an underlying end-stage renal disease. The remaining patients presented with normal blood count, liver function, and urea and creatinine levels. The documented MERS-CoV Ct values were 32–38 for four of the seven cases. Two patients (28.6%) had abnormal chest radiographic findings of bilateral infiltration. One patient (14.3%) required ventilator support, and two patients (28.6%) required oxygen supplementation. All the seven patients were discharged without complications.

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Natural killer cell lines in tumor immunotherapy
Min Cheng, Jian Zhang, Wen Jiang, Yongyan Chen, Zhigang Tian
Front Med.  2012, 6 (1): 56-66.   https://doi.org/10.1007/s11684-012-0177-7
Abstract   HTML   PDF (187KB)

Natural killer (NK) cells are considered to be critical players in anticancer immunity. However, cancers are able to develop mechanisms to escape NK cell attack or to induce defective NK cells. Current NK cell-based cancer immunotherapy is aimed at overcoming NK cell paralysis through several potential approaches, including activating autologous NK cells, expanding allogeneic NK cells, usage of stable allogeneic NK cell lines and genetically modifying fresh NK cells or NK cell lines. The stable allogeneic NK cell line approach is more practical for quality-control and large-scale production. Additionally, genetically modifying NK cell lines by increasing their expression of cytokines and engineering chimeric tumor antigen receptors could improve their specificity and cytotoxicity. In this review, NK cells in tumor immunotherapy are discussed, and a list of therapeutic NK cell lines currently undergoing preclinical and clinical trials of several kinds of tumors are reviewed.

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Personalized medicine of type 2 diabetes
Weiping Jia
Front Med.  2013, 7 (1): 1-3.   https://doi.org/10.1007/s11684-013-0241-y
Abstract   HTML   PDF (78KB)
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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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Coronavirus disease 2019 (COVID-19): a clinical update
Min Zhou, Xinxin Zhang, Jieming Qu
Front. Med..  2020, 14 (2): 126-135.   https://doi.org/10.1007/s11684-020-0767-8
Abstract   HTML   PDF (299KB)

Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has posed a significant threat to global health. It caused a total of 80 868 confirmed cases and 3101 deaths in Chinese mainland until March 8, 2020. This novel virus spread mainly through respiratory droplets and close contact. As disease progressed, a series of complications tend to develop, especially in critically ill patients. Pathological findings showed representative features of acute respiratory distress syndrome and involvement of multiple organs. Apart from supportive care, no specific treatment has been established for COVID-19. The efficacy of some promising antivirals, convalescent plasma transfusion, and tocilizumab needs to be investigated by ongoing clinical trials.

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Exploring the cancer genome in the era of next-generation sequencing
Hui Dong, Shengyue Wang
Front Med.  2012, 6 (1): 48-55.   https://doi.org/10.1007/s11684-012-0182-x
Abstract   HTML   PDF (154KB)

The emergence of next-generation sequencing technologies has led to dramatic advances in cancer genome studies. The increased efficiency and resolution of next-generation sequencing greatly facilitate the detection of genetic, genomic, and epigenomic alterations, such as single nucleotide mutations, small insertions and deletions, chromosomal rearrangements, copy number variations, and DNA methylation. Comprehensive analysis of cancer genomes through approaches of whole genome, exome, and transcriptome sequencing has significantly improved the understanding of cancer biology, diagnosis, and therapy. The present study briefly reviews the recent pioneering studies on cancer genome sequencing and provides an unprecedented insight into the landscape of genomic alterations in human sporadic cancers.

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Fibroblast growth factor 21: a novel metabolic regulator from pharmacology to physiology
Huating Li, Jing Zhang, Weiping Jia
Front Med.  2013, 7 (1): 25-30.   https://doi.org/10.1007/s11684-013-0244-8
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Fibroblast growth factor 21 (FGF21) is a member of the fibroblast growth factor family. It actually functions as endocrine hormones but does not regulate cell growth and differentiation. It is demonstrated that FGF21 acts on multiple tissue to coordinate carbohydrate and lipid metabolism, including enhancing insulin sensitivity, decreasing triglyceride concentrations, causing weight loss, ameliorating obesity-associated hyperglycemia and hyperlipidemia. Moreover, FGF21 also plays important roles in some physiological processes, such as fasting and feeding, growth hormone axis and thermogenic function of brown adipose tissue. Clinical relevance of FGF21 in humans is still unclear, and the basis and consequences of increased FGF21 in metabolic disease remain to be determined. Both the pharmacological actions and physiological roles make FGF21 attractive drug candidates for treating metabolic disease, but some questions remain to be answered. This article concentrates on recent advances in our understanding of FGF21.

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Developing effective tumor vaccines: basis, challenges and perspectives
XU Qingwen, CHEN Weifeng
Front. Med..  2007, 1 (1): 11-19.   https://doi.org/10.1007/s11684-007-0003-9
Abstract   PDF (291KB)
A remarkable advance in tumor immunology during the last decade is the elucidation of the antigenic basis of tumor recognition and destruction. A variety of tumor antigens have been identified using several strategies including conventional experiments and newly developed bioinformatics. Among these antigens, cancer/testis antigen (CT antigen) is considered to be the most promising target for immunotherapy by vaccination. Successful immunotherapy of tumors requires understanding of the natural relationship between the immune system and tumor in the status of differentiation, invasion and maturation. Continued progress in development of effective cancer vaccines depends on the identification of appropriate target antigens, the establishment of optimal immunization strategies without harmful autoimmune responses and the ability of manipulating tumor microenvironment to circumvent immune suppression and to augment the anti-tumor immune response.
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Progress in tumor vascular normalization for anticancer therapy: challenges and perspectives
Bingxue Shang, Zhifei Cao, Quansheng Zhou
Front Med.  2012, 6 (1): 67-78.   https://doi.org/10.1007/s11684-012-0176-8
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Antitumor angiogenic therapy has been shown promising in the treatment of several advanced cancers since the approval of the first antiangiogenic drug Avastin in 2004. Although the current antiangiogenic drugs reduce the density of tumor blood vessels and result in tumor shrinkage at the early stage of treatment, recent studies have shown that antiangiogenic therapy has transient and insufficient efficacy, resulting in tumor recurrence in patients after several months of treatment. Blockage of blood and oxygen supplies creates a hypoxic and acidic microenvironment in the tumor tissues, which fosters tumor cells to become more aggressive and metastatic. In 2001, Jain proposed tumor vascular normalization as an alternative approach to treating cancers based on the pioneering work on tumor blood vessels by several other researchers. At present, normalizing the disorganized tumor vasculature, rather than disrupting or blocking them, has emerged as a new option for anticancer therapy. Preclinical and clinical data have shown that tumor vascular normalization using monoclonal antibodies, proteins, peptides, small molecules, and pericytes resulted in decreased tumor size and reduced metastasis. However, current tumor vascular normalizing drugs display moderate anticancer efficacy. Accumulated data have shown that a variety of vasculogenic/angiogenic tumor cells and genes play important roles in tumor neovascularization, growth, and metastasis. Therefore, multiple-targeting of vasculogenic tumor cells and genes may improve the efficacy of tumor vascular normalization. To this end, the combination of antiangiogenic drugs with tumor vascular normalizing therapeutics, as well as the integration of Western medicine with traditional Chinese medicine, may provide a good opportunity for discovering novel tumor vascular normalizing drugs for an effective anticancer therapy.

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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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Hyperthermia on skin immune system and its application in the treatment of human papillomavirus-infected skin diseases
Xinghua Gao, Hongduo Chen
Front. Med..  2014, 8 (1): 1-5.   https://doi.org/10.1007/s11684-014-0309-3
Abstract   HTML   PDF (96KB)

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

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AML1-ETO driven acute leukemia: insights into pathogenesis and potential therapeutic approaches
Megan A. Hatlen, Lan Wang, Stephen D. Nimer
Front Med.  2012, 6 (3): 248-262.   https://doi.org/10.1007/s11684-012-0206-6
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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.

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Primary hypertrophic osteoarthropathy: an update
Zeng Zhang, Changqing Zhang, Zhenlin Zhang
Front Med.  2013, 7 (1): 60-64.   https://doi.org/10.1007/s11684-013-0246-6
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Digital clubbing, which has been recognized as a sign of systemic disease, is one of the most ancient diseases. However, the pathogenesis of clubbing and hypertrophic osteoarthropathy has hitherto been poorly understood. The study of a clinically indistinguishable idiopathic form (primary hypertrophic osteoarthropathy, PHO) provides an opportunity to understand the pathogenesis of hypertrophic osteoarthropathy. Current advances in the study of PHO are discussed. The impaired metabolism of prostaglandin E2 (PGE2) plays a central role in its pathogenesis.

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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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Dual faces of SH2-containing protein-tyrosine phosphatase Shp2/PTPN11 in tumorigenesis
Shuangwei Li, Diane DiFang Hsu, Hongyang Wang, Gen-Sheng Feng
Front Med.  2012, 6 (3): 275-279.   https://doi.org/10.1007/s11684-012-0216-4
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PTPN11, which encodes tyrosine phosphatase Shp2, is a critical gene mediating cellular responses to hormones and cytokines. Against original prediction as tumor suppressor for tyrosine phosphatases, PTPN11 was first identified as a proto-oncogene because activating mutations of this gene are associated with leukemogenesis. However, most recent experimental data suggest PTPN11/Shp2 acting as a tumor suppressor in hepatocarcinogenesis. This review focuses on the tumor-promoting or suppressing roles of the gene PTPN11/Shp2 in different cell types.

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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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Relationship of adrenomedullin expression and microvessel density and prognosis in smooth muscle tumor of uterus
JIANG Yuan, TIAN Xuehong, YUAN Jie, JIN Yuemei, TAN Yusong
Front. Med..  2007, 1 (4): 398-400.   https://doi.org/10.1007/s11684-007-0077-4
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The aim of this paper was to investigate the relationship between the expression of adrenomedullin (ADM) and microvessel density (MVD) and prognosis in smooth muscle tumor of uterus. The expression of ADM was detected using immunohistochemical staining in specimens from 15 normal controls, 28 cases of uterine leiomyoma (LE) and 19 cases of uterine leiomyosarcoma (LES). The MVD was assayed by immunostainting with CD34. There was a positive correlation between the ADM expression and MVD in LE and LES respectively (rs = 0.823, P<0.01; rs = 0.793, P<0.01). The expression of ADM in LE was statistically lower than that in LES (P<0.05). There was a positive correlation between the ADM expression and mitotic figures in LES (P<0.05): the more mitotic figures, the higher levels of the ADM expression and poor prognosis. The ADM is an important angiogenic factor in smooth muscle tumor of uterus. The ADM can be used as an accessory marker in estimating the malignant potency of LE and judging the pro gnosis of LES, and as a novel molecular target of anti-angiogenic and anticarcinogenic strategies.
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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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