Frontiers of Medicine

ISSN 2095-0217

ISSN 2095-0225(Online)

CN 11-5983/R

Postal Subscription Code 80-967

2018 Impact Factor: 1.847

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EDITORIAL
MINI-REVIEW
Understanding channel tropism in traditional Chinese medicine in the context of systems biology
Ping Liu, Songlin Liu, Gang Chen, Ping Wang
Front Med. 2013, 7 (3): 277-279.  
https://doi.org/10.1007/s11684-013-0273-3

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Channel tropism is investigated and developed through long-term clinical practice. In recent years, the development of channel tropism theory has attracted increasing attention. This study analyzed channel tropism theory and the problems associated with it. Results showed that this theory and systems biology have a similar holistic viewpoint. Systems biology could provide novel insights and platform in the study of channel tropism. Some problems in channel tropism theory, including pharmacology and action mechanism, were investigated.

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REVIEW
Identification of cancer gene fusions based on advanced analysis of the human genome or transcriptome
Lu Wang
Front Med. 2013, 7 (3): 280-289.  
https://doi.org/10.1007/s11684-013-0265-3

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Many gene fusions have been recognized as important diagnostic and/or prognostic markers in human malignancies. In recent years, novel gene fusions have been identified in cases without prior knowledge of the genetic background. Accompanied by a powerful computational data analysis method, new genome-wide screening approaches were used to detect cryptic genomic aberrations. This review focused on advanced genome-wide screening approaches in fusion gene identification, such as microarray-based approaches, next-generation sequencing, and NanoString nCounter gene expression system. The fundamental rationale and strategy for fusion gene identification using each biotech platform are also discussed.

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Therapeutic effects of thalidomide in hematologic disorders: a review
Miao Xu, Yu Hou, Lei Sheng, Jun Peng
Front Med. 2013, 7 (3): 290-300.  
https://doi.org/10.1007/s11684-013-0277-z

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

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Adiponectin: mechanisms and new therapeutic approaches for restoring diabetic heart sensitivity to ischemic post-conditioning
Tingting Wang, Shanglong Yao, Zhengyuan Xia, Michael G. Irwin
Front Med. 2013, 7 (3): 301-305.  
https://doi.org/10.1007/s11684-013-0283-1

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Systemic inflammatory response following myocardial ischemia-reperfusion injury (IRI) to a specific organ may cause injuries. Ischemic post-conditioning (IPostC) has emerged as a promising method for myocardial protection against IRI both in experimental and in clinical settings. Enhancement of endogenous nitric oxide (NO) is one of the major mechanisms by which IPostC confers cardioprotection. However, the sensitivity of the diabetic heart to IPostC is impaired and the underlying mechanism is unknown. Adiponectin (APN) is an adipocyte-derived plasma protein with anti-diabetic and anti-inflammatory properties. Plasma levels of APN are decreased in obese subjects and in patients with type 2 diabetes. APN supplementation has been shown to increase NO production and attenuate myocardial IRI in normal (non-diabetic) animals. However, the effect of APN on myocardial injury in diabetic subjects, especially its potential in restoring the sensitivity of the diabetic heart to IPostC has not been investigated. In the current paper, we discussed the possible reasons why the myocardium of diabetic subjects loses sensitivity to IPostC and also highlighted the potential effectiveness and mechanism of APN in restoring IPostC cardioprotection in diabetes. This review proposes to conduct studies that may facilitate the development of novel and optimal therapies to enhance cardioprotection in patients with severe diseases such as diabetes.

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Advancement of human leukocyte antigen-partially matched related hematopoietic stem cell transplantation
Xiaodong Mo, Xiaojun Huang
Front Med. 2013, 7 (3): 306-315.  
https://doi.org/10.1007/s11684-013-0279-x

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Allogeneic hematopoietic stem cell transplantation (HSCT) is one of the most effective options for hematological malignancies, and human leukocyte antigen-partially matched related donors (PMRDs) are a valuable option for HSCT. Several protocols (with or without ex vivo T-cell depletion (TCD)) have been established worldwide. TCD including CD34+ positive selection and CD3/CD19 depletion has successfully overcome the human leukocyte antigen disparity. However, TCD is associated with prolonged immune deficiencies, increased risks of infectious complications, and high transplantation-related mortality. PMRD HSCT without ex vivo TCD is well developed, and numerous patients have benefitted from it. Here, we review the literature on PMRD HSCT.

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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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Application of endoscopic techniques in orbital blowout fractures
Shu Zhang, Yinwei Li, Xianqun Fan
Front Med. 2013, 7 (3): 328-332.  
https://doi.org/10.1007/s11684-013-0271-5

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Minimally invasive surgical techniques, particularly endoscopic techniques, have revolutionized otolaryngeal surgery. Endoscopic techniques have been gradually applied in orbital surgery through the sinus inferomedial to the orbit and the orbital subperiosteal space. Endoscopic techniques help surgeons observe fractures and soft tissue of the posterior orbit to precisely place implants and protect vital structures through accurate, safe, and minimally invasive approaches. We reviewed the development of endoscopic techniques, the composition of endoscopic systems for orbital surgery, and the problems and developmental prospects of endoscopic techniques for simple orbital wall fracture repair.

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RESEARCH ARTICLE
The first avian influenza A (H7N9) viral infection in humans in Zhejiang Province, China: a death report
Enfu Chen, Fenjuan Wang, Huakun Lv, Yanjun Zhang, Hua Ding, Shelan Liu, Jian Cai, Li Xie, Xiaoping Xu, Chengliang Chai, Haiyan Mao, Jimin Sun, Junfen Lin, Zhao Yu, Lianhong Li, Zhiping Chen, Shichang Xia
Front Med. 2013, 7 (3): 333-344.  
https://doi.org/10.1007/s11684-013-0275-1

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This study reports the first death caused by a novel avian influenza A (H7N9) virus in Zhejiang Province, China. The patient had chronic hepatitis B and history of exposure to poultry. The patient initially complained of diarrhea and influenza-like symptoms on March 7 and 14 respectively. The disease progressed to severe pneumonia, sustained hypoxia, and coagulation abnormalities. The patient died on March 27 because of respiratory failure, multiple organ failure, and disseminated intravascular coagulation without oseltamivir treatment. This H7N9 virus from Zhejiang is highly similar to isolates obtained from Shanghai, Jiangsu, Anhui, etc. Analysis of hemagglutinin, neuramidinase, and matrix genes indicated that the isolates share the same avian origin, have low virulence, and are sensitive to oseltamivir, but are resistant to adamantine. Only the isolate that caused the fatality exhibited substitution of Q226I in the HA gene, which indicates a potentially enhanced human affinity. The secondary transmission rate was 1.6% (2/125). Only two health workers presented with influenza-like symptoms, and they subsequently tested negative for H7N9 RNA. In conclusion, underlying disease, late diagnosis, and untimely antiviral treatment are possible high-risk factors for infections and death caused by the low-pathogenicity avian influenza A (H7N9). Person-to-person transmission of the H7N9 virus was not detected among close contacts, but such transmission should be investigated in the future. Expanding and enhancing surveillance will help in the early discovery and diagnosis of suspected cases, which will reduce the number of severe cases and deaths.

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Capacity of human umbilical cord-derived mesenchymal stem cells to differentiate into sweat gland-like cells: a preclinical study
Siming Yang, Kui Ma, Changjiang Feng, Yan Wu, Yao Wang, Sha Huang, Xiaobing Fu
Front Med. 2013, 7 (3): 345-353.  
https://doi.org/10.1007/s11684-013-0282-2

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Human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) possess various advantageous properties, including self-renewal, extended proliferation potential, multi-lineage differentiation potential and capacity for differentiating into sweat gland-like cells in certain conditions. However, little is known about the effect of clinical-grade culture conditions on these properties and on the differentiative potential of hUC-MSCs. In this study, we sought to investigate the properties of hUC-MSCs expanded with animal serum free culture media (ASFCM) in order to determine their potential for differentiation into sweat gland-like cells. We found that primary cultures of hUC-MSCs could be established with ASFCM. Moreover, cells cultured in ASFCM showed vigorous proliferation comparable to those of cells grown in classical culture conditions containing fetal bovine serum (FBS). Morphology of hUC-MSCs cultured in ASFCM was comparable to those of cells grown under classical culture conditions, and hUC-MSCs grown in both of the two culture conditions tested showed the typical antigen profile of MSCs—positive for CD29, CD44, CD90, and CD105, and negative for CD34 and CD45, as expected. Chromosomal aberration assay revealed that the cells were stable after long-term culture under both culture conditions. Like normal cultured MSCs, hUC-MSCs induced under ASFCM conditions exhibited expression of the same markers (CEA, CK14 and CK19) and developmental genes (EDA and EDAR) that are characteristic of normal sweat gland cells. Taken together, our findings indicate that the classical culture medium used to differentiate hUC-MSCs into sweat gland-like cells can be replaced safely by ASFCM for clinical purposes.

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Treatment outcomes of pulmonary tuberculosis in the past decade in the mainland of China: a meta-analysis
Xiangwei Li, Yu Yang, Jianmin Liu, Feng Zhou, Wei Cui, Ling Guan, Fei Shen, Cong Gao, Mufei Li, Qi Jin, Lei Gao
Front Med. 2013, 7 (3): 354-366.  
https://doi.org/10.1007/s11684-013-0257-3

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Due to the implementation of directly observed treatment strategy (DOTS), China has made a significant achievement in tackling the tuberculosis (TB) epidemic in the 1990s. However, only half of regions in China met or exceeded the 85% rate of treatment success target. The aim of the present study is to summarize the treatment outcomes of smear-positive pulmonary TB in the mainland of China in the past decade using meta-analysis based on systematic review of published observational studies. A total of 50 eligible articles (58 studies) were identified and included in this study. The summarized treatment success rates were 93.9% (95% CI, 92.8%–94.7%) for new cases and 85.4% (95% CI, 83.0%–87.6%) for previously treated cases, and the summarized cured rate were 92.2% (95% CI, 90.9%–93.3%) and 81.2% (95% CI, 79.1%–83.1%), respectively. A remarkable increase of rates for treatment success and cure was observed in the 1990s. After 2000, the summarized treatment outcomes were tending towards stability. In addition, geographic areas, type of the data and administrative level of the hospital were also found to influence the estimates of the treatment outcomes. Results of the present study clearly show, in general, that the pulmonary TB treatment achieved significant success in the past decade in the mainland of China. However, it needs to be further strengthened in the central and west areas.

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A modified chronic ocular hypertension rat model for retinal ganglion cell neuroprotection
Lichun Zhong
Front Med. 2013, 7 (3): 367-377.  
https://doi.org/10.1007/s11684-013-0266-2

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This study aimed to modify a chronic ocular hypertension (OHT) rat model to screen for potential compounds to protect retinal ganglion cells (RGCs) from responding to increased intraocular pressure (IOP). A total of 266 rats were prepared and randomly grouped according to different time-points, namely, weeks 3, 8, 16, and 24. Rats were sedated and eye examination was performed to score as the corneal damage on a scale of 1 to 4. The OHT rat model was created via the injection of a hypertonic saline solution into the episcleral veins once weekly for two weeks. OHT was identified when the IOP at week 0 was≥6 mmHg than that at week -2 for the same eye. Viable RGCs were labeled by injecting 4% FluoroGold. Rats were sacrificed, and the eyes were enucleated and fixed. The fixed retinas were dissected to prepare flat whole-mounts. The viable RGCs were visualized and imaged. The IOP (meanβ±βSD) was calculated, and data were analyzed by the paired t-test and one-way ANOVA. The OHT model was created in 234 of 266 rats (87.97%), whereas 32 rats (12.03%) were removed from the study because of the absence of IOP elevation (11.28%) and/or corneal damage scores over 4 (0.75%). IOP was elevated by as much as 81.35% for 24 weeks. The average IOP was (16.68β±β0.98)βmmHg in non-OHT eyes (n = 234), but was (27.95±0.97)βmmHg in OHT eyes (n = 234). Viable RGCs in the OHT eyes were significantly decreased in a time-dependent manner by 29.41%, 38.24%, 55.32%, and 59.30% at weeks 3, 8, 16, and 24, respectively, as compared to viable RGCs in the non-OHT eyes (P<β0.05). The OHT model was successfully created in 88% of the rats. The IOP in the OHT eyes was elevated by approximately 81% for 24 weeks. The number of viable RGCs was decreased by 59% of the rats in a time-dependent manner. The modified OHT model may provide an effective and reliable method for screening drugs to protect RGCs from glaucoma.

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Epidemiological study of a von Hippel-Lindau family in northwest China
Jingyao Zhang, Dapeng Wu, Hong Ai, Jigang Bai, Shunbin Dong, Qinling Yang, Kai Qu, Lei Zhou, Xinsen Xu, Chang Liu
Front Med. 2013, 7 (3): 378-385.  
https://doi.org/10.1007/s11684-013-0276-0

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von Hippel-Lindau (VHL) disease is a rare, inherited neoplastic disease characterized by hemangioblastomas (HBL) of the central nervous system (CNS), retinal angiomas, renal cell carcinomas (RCC), pancreatic endocrine tumors (PETs), pheochromocytomas, paragangliomas, and visceral cysts. We encountered a large VHL family in northwest China and conducted a systematic screening of the family members based on their epidemiological and clinical characteristics. A self-designed questionnaire was used to collect the general sociodemographic and health information of the family members. For the preliminary family screening, physical examination and abdomen B ultrasonography were performed. The suspected patients were subjected to cranial computerized tomography and fundus examination. The clinical data of the patients with confirmed VHL disease were collected from hospital records. A total of 63 lineal descendants in six generations were observed in the family (generations O, A, B, C, D, E), including 9 dead suspected cases (6 males, 3 females) and 10 living cases (2 males, 8 females). Among the 10 living cases, 4, 2, 1, 3, 4, 8, and 2 manifested HBLs of the CNS, PETs, RCC, pancreatic cysts, renal cysts, pheochromocytomas (4 hemi and 4 bilateral), and paragangliomas, respectively. Data showed that the morbidity of VHL disease in generation C was lower than that in generation B, but the age of onset was younger. This study is the first to report VHL disease in northwest China and VHL-associated PET cases in Chinese. Therefore, follow-up checkups of the family should be focused on younger generations. Proper family screening protocols should be followed for the treatment of patients with VHL disease.

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CASE REPORT
Trauma-induced “Macklin effect” with pneumothorax and large pneumomediastinum, disguised by allergy
Salomone Di Saverio, Kenji Kawamukai, Andrea Biscardi, Silvia Villani, Luca Zucchini, Gregorio Tugnoli
Front Med. 2013, 7 (3): 386-388.  
https://doi.org/10.1007/s11684-013-0278-y

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A 56-year-old man presented spontaneously to the Emergency Department complaining of facial and neck oedema after assumption of nonsteroidal anti-inflammatory drugs (NSAIDS). The triage nurse assigned the patient to Accident & Emergency (A&E) doctor as probable allergic reaction to NSAIDS. Chest X-ray (CXR), ordered after 24 hours, revealed a huge subcutaneous chest and neck emphysema without clearly visible pneumothorax. Subsequent chest CT scan showed a small left pneumothorax and a large amount of air in the mediastinum. The patient was conservatively treated since he was eupnoeic and hemodynamically stable. The pathophysiology of pneumomediastinum was first described by Macklin in 1939. The Macklin effect involves alveolar ruptures with air dissection along bronchovascular sheaths to the mediastinum. In this case the patient did not report in his history a recent blunt thoracic trauma and the initial suspicion of an allergic reaction has prevented physicians to immediately achieve the correct diagnosis.

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COMMENTARY
Cultural differences define diagnosis and genomic medicine practice: implications for undiagnosed diseases program in China
Xiaohong Duan, Thomas Markello, David Adams, Camilo Toro, Cynthia Tifft, William A. Gahl, Cornelius F. Boerkoel
Front Med. 2013, 7 (3): 389-394.  
https://doi.org/10.1007/s11684-013-0281-3

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Despite the current acceleration and increasing leadership of Chinese genetics research, genetics and its clinical application have largely been imported to China from the Occident. Neither genetics nor the scientific reductionism underpinning its clinical application is integral to the traditional Chinese worldview. Given that disease concepts and their incumbent diagnoses are historically derived and culturally meaningful, we hypothesize that the cultural expectations of genetic diagnoses and medical genetics practice differ between the Occident and China. Specifically, we suggest that an undiagnosed diseases program in China will differ from the recently established Undiagnosed Diseases Program at the United States National Institutes of Health; a culturally sensitive concept will integrate traditional Chinese understanding of disease with the scientific reductionism of Occidental medicine.

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ERRATUM
16 articles