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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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Cited: Crossref(240) WebOfScience(208)
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
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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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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
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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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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
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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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Protecting healthcare personnel from 2019-nCoV infection risks: lessons and suggestions
Zhiruo Zhang, Shelan Liu, Mi Xiang, Shijian Li, Dahai Zhao, Chaolin Huang, Saijuan Chen
Front. Med.    2020, 14 (2): 229-231.   https://doi.org/10.1007/s11684-020-0765-x
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The outbreak of a novel coronavirus disease (COVID-19, caused by the 2019-nCoV infection) in December 2019 is one of the most severe public health emergencies since the founding of People’s Republic of China in 1949. Healthcare personnel (HCP) nationwide are facing heavy workloads and high risk of infection, especially those who care for patients in Hubei Province. Sadly, as of February 20, 2020, over two thousand COVID-19 cases are confirmed among HCP from 476 hospitals nationwide, with nearly 90% of them from Hubei Province. Based on literature search and interviews with some HCP working at Wuhan, capital city of Hubei, we have summarized some of the effective measures taken to reduce infection among HCP, and also made suggestions for improving occupational safety during an infectious disease outbreak. The experience and lessons learned should be a valuable asset for international health community to contain the ongoing COVID-19 epidemic around the world.

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iTRAQ-based quantitative proteomic analysis on differentially expressed proteins of rat mandibular condylar cartilage induced by reducing dietary loading
Liting Jiang,Yinyin Xie,Li Wei,Qi Zhou,Ning Li,Xinquan Jiang,Yiming Gao
Front. Med.    2017, 11 (1): 97-109.   https://doi.org/10.1007/s11684-016-0496-1
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As muscle activity during growth is considerably important for mandible quality and morphology, reducing dietary loading directly influences the development and metabolic activity of mandibular condylar cartilage (MCC). However, an overall investigation of changes in the protein composition of MCC has not been fully described in literature. To study the protein expression and putative signaling in vivo, we evaluated the structural changes of MCC and differentially expressed proteins induced by reducing functional loading in rat MCC at developmental stages. Isobaric tag for relative and absolute quantitation-based 2D nano-high performance liquid chromatography (HPLC) and matrix-assisted laser desorption/ionization time-of-flight/ time-of-flight (MALDI-TOF/TOF) technologies were used. Global protein profiling, KEGG and PANTHER pathways, and functional categories were analyzed. Consequently, histological and tartrate-resistant acid phosphatase staining indicated the altered histological structure of condylar cartilage and increased bone remodeling activity in hard-diet group. A total of 805 differentially expressed proteins were then identified. GO analysis revealed a significant number of proteins involved in the metabolic process, cellular process, biological regulation, localization, developmental process, and response to stimulus. KEGG pathway analysis also suggested that these proteins participated in various signaling pathways, including calcium signaling pathway, gap junction, ErbB signaling pathway, and mitogen-activated protein kinase signaling pathway. Collagen types I and II were further validated by immunohistochemical staining and Western blot analysis. Taken together, the present study provides an insight into the molecular mechanism of regulating condylar growth and remodeling induced by reducing dietary loading at the protein level.

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2019 novel coronavirus outbreak: a quiz or final exam?
Jiuyang Xu, Yijun Chen, Hao Chen, Bin Cao
Front. Med.    2020, 14 (2): 225-228.   https://doi.org/10.1007/s11684-020-0753-1
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The 2019 novel coronavirus (2019-nCoV) is an emerging pathogen and is threatening the global health. Strikingly, more than 28 000 cases and 550 deaths have been reported within two months from disease emergence. Armed with experience from previous epidemics in the last two decades, clinicians, scientists, officials, and citizens in China are all contributing to the prevention of further 2019-nCoV transmission. Efficient preliminary work has enabled us to understand the basic characteristics of 2019-nCoV, but there are still many unanswered questions. It is too early now to judge our performance in this outbreak. Continuous and strengthened efforts should be made not only during the epidemic, but also afterwards in order to prepare for any incoming challenges.

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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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Development of an artificial intelligence diagnostic model based on dynamic uncertain causality graph for the differential diagnosis of dyspnea
Yang Jiao, Zhan Zhang, Ting Zhang, Wen Shi, Yan Zhu, Jie Hu, Qin Zhang
Front. Med.    2020, 14 (4): 488-497.   https://doi.org/10.1007/s11684-020-0762-0
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Dyspnea is one of the most common manifestations of patients with pulmonary disease, myocardial dysfunction, and neuromuscular disorder, among other conditions. Identifying the causes of dyspnea in clinical practice, especially for the general practitioner, remains a challenge. This pilot study aimed to develop a computer-aided tool for improving the efficiency of differential diagnosis. The disease set with dyspnea as the chief complaint was established on the basis of clinical experience and epidemiological data. Differential diagnosis approaches were established and optimized by clinical experts. The artificial intelligence (AI) diagnosis model was constructed according to the dynamic uncertain causality graph knowledge-based editor. Twenty-eight diseases and syndromes were included in the disease set. The model contained 132 variables of symptoms, signs, and serological and imaging parameters. Medical records from the electronic hospital records of Suining Central Hospital were randomly selected. A total of 202 discharged patients with dyspnea as the chief complaint were included for verification, in which the diagnoses of 195 cases were coincident with the record certified as correct. The overall diagnostic accuracy rate of the model was 96.5%. In conclusion, the diagnostic accuracy of the AI model is promising and may compensate for the limitation of medical experience.

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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&lt;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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Advances in COVID-19: the virus, the pathogenesis, and evidence-based control and therapeutic strategies
Guangbiao Zhou, Saijuan Chen, Zhu Chen
Front. Med.    2020, 14 (2): 117-125.   https://doi.org/10.1007/s11684-020-0773-x
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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.

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Combination of western medicine and Chinese traditional patent medicine in treating a family case of COVID-19
Li Ni, Ling Zhou, Min Zhou, Jianping Zhao, Dao Wen Wang
Front. Med.    2020, 14 (2): 210-214.   https://doi.org/10.1007/s11684-020-0757-x
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In December 2019, an outbreak of novel coronavirus (2019-nCoV) occurred in Wuhan, Hubei Province, China. By February 14, 2020, it has led to 66 492 confirmed patients in China and high mortality up to ~2.96% (1123/37 914) in Wuhan. Here we report the first family case of coronavirus disease 2019 (COVID-19) confirmed in Wuhan and treated using the combination of western medicine and Chinese traditional patent medicine Shuanghuanglian oral liquid (SHL). This report describes the identification, diagnosis, clinical course, and management of three cases from a family, suggests the expected therapeutic effects of SHL on COVID-19, and warrants further clinical trials.

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Clinical characteristics of 19 neonates born to mothers with COVID-19
Wei Liu, Jing Wang, Wenbin Li, Zhaoxian Zhou, Siying Liu, Zhihui Rong
Front. Med.    2020, 14 (2): 193-198.   https://doi.org/10.1007/s11684-020-0772-y
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The aim of this study was to investigate the clinical characteristics of neonates born to SARS-CoV-2 infected mothers and increase the current knowledge on the perinatal consequences of COVID-19. Nineteen neonates were admitted to Tongji Hospital from January 31 to February 29, 2020. Their mothers were clinically diagnosed or laboratory-confirmed with COVID-19. We prospectively collected and analyzed data of mothers and infants. There are 19 neonates included in the research. Among them, 10 mothers were confirmed COVID-19 by positive SARS-CoV-2 RT-PCR in throat swab, and 9 mothers were clinically diagnosed with COVID-19. Delivery occurred in an isolation room and neonates were immediately separated from the mothers and isolated for at least 14 days. No fetal distress was found. Gestational age of the neonates was 38.6±1.5 weeks, and average birth weight was 3293±425 g. SARS-CoV-2 RT-PCR in throat swab, urine, and feces of all neonates were negative. SARS-CoV-2 RT-PCR in breast milk and amniotic fluid was negative too. None of the neonates developed clinical, radiologic, hematologic, or biochemical evidence of COVID-19. No vertical transmission of SARS-CoV-2 and no perinatal complications in the third trimester were found in our study. The delivery should occur in isolation and neonates should be separated from the infected mothers and care givers.

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Back to the spring of 2020: facts and hope of COVID-19 outbreak
Guangbiao Zhou, Saijuan Chen, Zhu Chen
Front. Med.    2020, 14 (2): 113-116.   https://doi.org/10.1007/s11684-020-0758-9
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Adoptive cell transfer therapy for hepatocellular carcinoma
Renyu Zhang, Zhao Zhang, Zekun Liu, Ding Wei, Xiaodong Wu, Huijie Bian, Zhinan Chen
Front. Med.    2019, 13 (1): 3-11.   https://doi.org/10.1007/s11684-019-0684-x
Abstract   HTML   PDF (141KB)

Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide. This malignancy is associated with poor prognosis and high mortality. Novel approaches for prolonging the overall survival of patients with advanced HCC are urgently needed. The antitumor activities of adoptive cell transfer therapy (ACT), such as strategies based on tumor-infiltrating lymphocytes and cytokine-induced killer cells, are more effective than those of traditional strategies. Currently, chimeric antigen receptor T-cell (CAR-T) immunotherapy has achieved numerous breakthroughs in the treatment of hematological malignancies, including relapsed or refractory lymphoblastic leukemia and refractory large B-cell lymphoma. Nevertheless, this approach only provides a modest benefit in the treatment of solid tumors. The clinical results of CAR-T immunotherapy for HCC that could be obtained at present are limited. Some published studies have demonstrated that CAR-T could inhibit tumor growth and cause severe side effects. In this review, we summarized the current application of ACT, the challenges encountered by CAR-T technology in HCC treatment, and some possible strategies for the future direction of immunotherapeutic research.

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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
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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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COVID-19 containment: China provides important lessons for global response
Shuxian Zhang, Zezhou Wang, Ruijie Chang, Huwen Wang, Chen Xu, Xiaoyue Yu, Lhakpa Tsamlag, Yinqiao Dong, Hui Wang, Yong Cai
Front. Med.    2020, 14 (2): 215-219.   https://doi.org/10.1007/s11684-020-0766-9
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The world must act fast to contain wider international spread of the epidemic of COVID-19 now. The unprecedented public health efforts in China have contained the spread of this new virus. Measures taken in China are currently proven to reduce human-to-human transmission successfully. We summarized the effective intervention and prevention measures in the fields of public health response, clinical management, and research development in China, which may provide vital lessons for the global response. It is really important to take collaborative actions now to save more lives from the pandemic of COVID-19.

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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
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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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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
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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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Mesenchymal stem cells and immune disorders: from basic science to clinical transition
Shihua Wang, Rongjia Zhu, Hongling Li, Jing Li, Qin Han, Robert Chunhua Zhao
Front. Med.    2019, 13 (2): 138-151.   https://doi.org/10.1007/s11684-018-0627-y
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As a promising candidate seed cell type in regenerative medicine, mesenchymal stem cells (MSCs) have attracted considerable attention. The unique capacity of MSCs to exert a regulatory effect on immunity in an autologous/allergenic manner makes them an attractive therapeutic cell type for immune disorders. In this review, we discussed the current knowledge of and advances in MSCs, including its basic biological properties, i.e., multilineage differentiation, secretome, and immunomodulation. Specifically, on the basis of our previous work, we proposed three new concepts of MSCs, i.e., “subtotipotent stem cell” hypothesis, MSC system, and “Yin and Yang” balance of MSC regulation, which may bring new insights into our understanding of MSCs. Furthermore, we analyzed data from the Clinical Trials database (http://clinicaltrials.gov) on registered clinical trials using MSCs to treat a variety of immune diseases, such as graft-versus-host disease, systemic lupus erythematosus, and multiple sclerosis. In addition, we highlighted MSC clinical trials in China and discussed the challenges and future directions in the field of MSC clinical application.

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Dental stem cell and dental tissue regeneration
Qiming Zhai, Zhiwei Dong, Wei Wang, Bei Li, Yan Jin
Front. Med.    2019, 13 (2): 152-159.   https://doi.org/10.1007/s11684-018-0628-x
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The teeth are highly differentiated chewing organs formed by the development of tooth germ tissue located in the jaw and consist of the enamel, dentin, cementum, pulp, and periodontal tissue. Moreover, the teeth have a complicated regulatory mechanism, special histologic origin, diverse structure, and important function in mastication,, articulation,, and aesthetics. These characteristics, to a certain extent, greatly complicate the research in tooth regeneration. Recently, new ideas for tooth and tissue regeneration have begun to appear with rapid developments in the theories and technologies in tissue engineering. Numerous types of stem cells have been isolated from dental tissue, such as dental pulp stem cells (DPSCs), stem cells isolated from human pulp of exfoliated deciduous teeth (SHED), periodontal ligament stem cells (PDLSCs), stem cells from apical papilla (SCAPs), and dental follicle cells (DFCs). All these cells can regenerate the tissue of tooth. This review outlines the cell types and strategies of stem cell therapy applied in tooth regeneration, in order to provide theoretical basis for clinical treatments.

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The FGF metabolic axis
Xiaokun Li
Front. Med.    2019, 13 (5): 511-530.   https://doi.org/10.1007/s11684-019-0711-y
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Members of the fibroblast growth factor (FGF) family play pleiotropic roles in cellular and metabolic homeostasis. During evolution, the ancestor FGF expands into multiple members by acquiring divergent structural elements that enable functional divergence and specification. Heparan sulfate-binding FGFs, which play critical roles in embryonic development and adult tissue remodeling homeostasis, adapt to an autocrine/paracrine mode of action to promote cell proliferation and population growth. By contrast, FGF19, 21, and 23 coevolve through losing binding affinity for extracellular matrix heparan sulfate while acquiring affinity for transmembrane α-Klotho (KL) or β-KL as a coreceptor, thereby adapting to an endocrine mode of action to drive interorgan crosstalk that regulates a broad spectrum of metabolic homeostasis. FGF19 metabolic axis from the ileum to liver negatively controls diurnal bile acid biosynthesis. FGF21 metabolic axes play multifaceted roles in controlling the homeostasis of lipid, glucose, and energy metabolism. FGF23 axes from the bone to kidney and parathyroid regulate metabolic homeostasis of phosphate, calcium, vitamin D, and parathyroid hormone that are important for bone health and systemic mineral balance. The significant divergence in structural elements and multiple functional specifications of FGF19, 21, and 23 in cellular and organismal metabolism instead of cell proliferation and growth sufficiently necessitate a new unified and specific term for these three endocrine FGFs. Thus, the term “FGF Metabolic Axis,” which distinguishes the unique pathways and functions of endocrine FGFs from other autocrine/paracrine mitogenic FGFs, is coined.

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Prevention and treatment of pancreatic fistula after pancreatic body and tail resection: current status and future directions
Li Jiang, Deng Ning, Xiao-ping Chen
Front. Med.    2020, 14 (3): 251-261.   https://doi.org/10.1007/s11684-019-0727-3
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Postoperative pancreatic fistula (POPF) is the most common and critical complication after pancreatic body and tail resection. How to effectively reduce the occurrence of pancreatic fistula and conduct timely treatment thereafter is an urgent clinical issue to be solved. Recent research standardized the definition of pancreatic fistula and stressed the correlation between POPF classification and patient prognosis. According to the literature, identification of the risk factors for pancreatic fistula contributed to lowering the rate of the complication. Appropriate management of the pancreatic stump and perioperative treatment are of great significance to reduce the rate of POPF in clinical practice. After the occurrence of POPF, the treatment of choice should be determined according to the classification of the pancreatic fistula. However, despite the progress and promising treatment approaches, POPF remains to be a clinical issue that warrants further studies in the future.

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Developments in cancer prevention and treatment using traditional Chinese medicine
Hongsheng Lin, Jie Liu, Ying Zhang
Front Med    2011, 5 (2): 127-133.   https://doi.org/10.1007/s11684-011-0137-7
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Through the joint efforts of several generations of practitioners in traditional Chinese medicine (TCM) and integrated medicine of oncology, we have made some achievements in cancer treatment using TCM in over 50 years, including treatment concepts, methods, and basic and clinical research. Currently, TCM plays an indispensable role in cancer prevention and treatment. However, we also clearly recognize that there are some issues that have yet to be resolved. In the future, cancer treated with TCM will face unprecedented opportunities and challenges. This article reviews the developments of TCM in the treatment of cancer.

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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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China’s local governments are combating COVID-19 with unprecedented responses ---- from a Wenzhou governance perspective
Fanghua Gong, Yong Xiong, Jian Xiao, Li Lin, Xiaodong Liu, Dezhong Wang, Xiaokun Li
Front. Med.    2020, 14 (2): 220-224.   https://doi.org/10.1007/s11684-020-0755-z
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The COVID-19 caused by a novel strain of coronavirus has been spreading rapidly since its occurrence in December 2019. It is highly communicable through human-to-human transmission. China has been making unprecedented efforts in treating the confirmed cases, identifying and isolating their close contacts and suspected cases to control the source of infection and cut the route of transmission. China’s devotion in handling this epidemic has effectively and efficiently curbed communication domestically and across the border. Representative measures adopted by Wenzhou, the worst hit city out of Hubei Province, are examined to elucidate those massive undertakings with the aim of enhancing international understanding and building global rapport in fighting this evolving epidemic situation.

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Cited: Crossref(6) WebOfScience(5)
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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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
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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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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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