Frontiers of Medicine

ISSN 2095-0217

ISSN 2095-0225(Online)

CN 11-5983/R

Postal Subscription Code 80-967

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REVIEW
Partial liver transplantation
Nianqiao GONG, Xiaoping CHEN
Front Med. 2011, 5 (1): 1-7.  
https://doi.org/10.1007/s11684-010-0105-7

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Partial liver transplantation, including reduced-size liver transplantation, split liver transplantation, and living donor liver transplantation, has been developed with several innovative techniques because of donor shortage. Reduced-size liver transplantation is based on Couinaud’s anatomical classification, benefiting children and small adult recipients but failing to relieve the overall donor shortage. Split liver transplantation provides chances to two or even more recipients when only one liver graft is available. The splitting technique must follow stricter anatomical and physiological criteria either ex situ or in situ to ensure long-term quality. The first and most important issue involving living donor liver transplantation is donor safety. Before surgery, a series of donor evaluations—including anatomical, liver volume, and liver function evaluations—is indispensable, followed by ethnic agreement. At different recipient conditions, auxiliary liver transplantation and auxiliary partial orthotopic liver transplantation, which employ piggyback techniques, are good alternatives. Partial liver transplantation enriches the practice and knowledge of the transplant society.

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The influence of brain death on donor liver and the potential mechanisms of protective intervention
Shui-Jun ZHANG, Tao WANG
Front Med. 2011, 5 (1): 8-14.  
https://doi.org/10.1007/s11684-011-0109-y

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Brain-dead donors have become one of the main sources of organs for transplantation in Western countries. The quality of donor organs is closely related to the outcome of the transplantation. Experimental studies have confirmed the inferior graft survival of livers from brain-dead donors compared with those from living donors. Studies conducted in the past 10 years have shown that brain death is associated with effects on the decreased donor organ quality. However, whether the decrease in the viability of donor organs is caused by brain death or by the events before and after brain death remains uncertain. The purpose of this review is to introduce the advances and controversies regarding the influence of brain death on the viability of donor livers and to summarize the mechanisms of the different protective interventions for donor livers.

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Bioartificial liver devices: Perspectives on the state of the art
Yi-Tao DING, MM, Xiao-Lei SHI, MD
Front Med. 2011, 5 (1): 15-19.  
https://doi.org/10.1007/s11684-010-0110-x

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Acute liver failure remains a significant cause of morbidity and mortality. Bioartificial liver (BAL) devices have been in development for more than 20 years. Such devices aim to temporarily take over the metabolic and excretory functions of the liver until the patients’ own liver has recovered or a donor liver becomes available for transplant. The important issues include the choice of cell materials and the design of the bioreactor. Ideal BAL cell materials should be of good viability and functionality, easy to access, and exclude immunoreactive and tumorigenic cell materials. Unfortunately, the current cells in use in BAL do not meet these requirements. One of the challenges in BAL development is the improvement of current materials; another key point concerning cell materials is the coculture of different cells. The bioreactor is an important component of BAL, because it determines the viability and function of the hepatocytes within it. From the perspective of bioengineering, a successful and clinically effective bioreactor should mimic the structure of the liver and provide an in vivo-like microenvironment for the growth of hepatocytes, thereby maintaining the cells’ viability and function to the maximum extent. One future trend in the development of the bioreactor is to improve the oxygen supply system. Another direction for future research on bioreactors is the application of biomedical materials. In conclusion, BAL is, in principle, an important therapeutic strategy for patients with acute liver failure, and may also be a bridge to liver transplantation. It requires further research and development, however, before it can enter clinical practice.

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Integrated management of cardiac failure: the cardiac failure clinic
Daniel LOISANCE
Front Med. 2011, 5 (1): 20-25.  
https://doi.org/10.1007/s11684-011-0106-1

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The prevalence of the risk factors and the risk of cardiac failure are both increasing in China. This might be the consequence of the changes of the life conditions (emigration to the urban areas, changes in the diet and life style, lack of physical exercise, etc.). The wide range of clinical presentations of cardiac failure (acute or chronic) and of therapeutic approaches (medical or surgical) makes necessary the integration within the same structure of the various experts involved in the diagnosis and the treatment of cardiac diseases. Technologic and human resources required to offer all the options represent a multifaceted commitment which should be focused optimally in dedicated centers. In these centers, collaboration should replace competition between the medical and the surgical cardiac specialists. Development of team work should permit to optimize the cost efficacy of the treatments. Most of all, such a structure will facilitate the translation of innovative therapies between the research centers and clinical facilities.

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Therapeutic potential of stem cell in liver regeneration
Jinzheng LI, Min LI, Bolin NIU, Jianping GONG
Front Med. 2011, 5 (1): 26-32.  
https://doi.org/10.1007/s11684-011-0107-0

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Liver transplantation is the only life-saving procedure for patients with end-stage liver disease. However, its potential benefits are hampered by many disadvantages, such as the relative shortage of donors, operative risks, and high costs. These issues have prompted the search for new alternative therapies for irreversible liver disease. Stem cell therapy, with the ability for self-renewal and potential for multilineage differentiation, is a promising alternative approach. Several studies have demonstrated that transplantation of hepatic stem/progenitor cells or hepatocyte-like cells derived from multipotent stem cells leads to donor cell-mediated repopulation of the liver and improved survival rates in experimental models of liver disease. However, a registered clinical application based on stem cell technology will take at least an additional 5 to 10 years because of some limitations; e.g. the lack of suitable cell sources and risk of teratoma formation. This review summarizes the general understanding of the therapeutic potentials of stem cells in liver disease, including the sources, mechanisms, and delivery methods of hepatic stem cells in liver regeneration, and discusses some challenges for their therapeutic application.

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Regulatory factors of mesenchymal stem cell migration into injured tissues and their signal transduction mechanisms
Li LI, Jianxin JIANG
Front Med. 2011, 5 (1): 33-39.  
https://doi.org/10.1007/s11684-011-0114-1

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Adult stem cells hold great promise for wound healing and tissue regeneration. Mesenchymal stem cells (MSCs), for example, have been shown to play a role in tissue repair. Research has shown that endogenous bone marrow MSCs or exogenously delivered MSCs migrate to the sites of injury and participate in the repair process. The precise mechanisms underlying migration of MSCs into the injured tissue are still not fully understood, although multiple signaling pathways and molecules were reported, including both chemoattractive factors and endogenous electric fields at wounds. This review will briefly summarize the regulatory facors and signaling transduction pathways involved in migration of MSCs. A better understanding of the molecular mechanisms involved in the migration of MSCs will help us to develop new stem cell-based therapeutic strategies in regenerative medicine.

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Stem cell niches and endogenous electric fields in tissue repair
Li LI, Jianxin JIANG
Front Med. 2011, 5 (1): 40-44.  
https://doi.org/10.1007/s11684-011-0108-z

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Adult stem cells are responsible for homeostasis and repair of many tissues. Endogenous adult stem cells reside in certain regions of organs, known as the stem cell niche, which is recognized to have an important role in regulating tissue maintenance and repair. In wound healing and tissue repair, stem cells are mobilized and recruited to the site of wound, and participate in the repair process. Many regulatory factors are involved in the stem cell-based repair process, including stem cell niches and endogenous wound electric fields, which are present at wound tissues and proved to be important in guiding wound healing. Here we briefly review the role of stem cell niches and endogenous electric fields in tissue repair, and hypothesize that endogenous electric fields become part of stem cell niche in the wound site.

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Arsenic in the treatment of newly diagnosed acute promyelocytic leukemia: current status and future research direction
Jiong HU
Front Med. 2011, 5 (1): 45-52.  
https://doi.org/10.1007/s11684-011-0117-y

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Acute promyelocytic leukemia (APL) is a subtype of acute myeloid leukemia. In past decades, intensive studies on the biology and treatment of this disease have resulted in a remarkably thorough understanding of its pathogenesis and improvement of treatment outcomes. In particular, the introduction of all-trans retinoic acid to conventional chemotherapy improved dramatically the remission and survival rates of APL patients and consequently became the major treatment modality for it. In the last decade, the groundbreaking development of arsenic further improved the survival rate of APL patients. As the most active agent in APL, arsenic directly degrades the PML-RARα fusion transcript, leading to the differentiation and apoptosis of leukemia cells and the potential eradication of APL leukemia-initiating cells (LICs), thus making the disease a potentially curable type of leukemia. More notably, the recent development of oral arsenic compounds may further enhance not only clinical outcomes but also the convenience of patients, which may dramatically change the APL clinical scenario in the near future.

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Lobectomy by video-assisted thoracoscopic surgery (VATS) for early stage of non-small cell lung cancer
Min ZHU, Xiang-Ning FU, Xiao-Ping CHEN
Front Med. 2011, 5 (1): 53-60.  
https://doi.org/10.1007/s11684-011-0121-2

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Video-assisted thoracoscopic surgery (VATS) provides a new approach for treating early-stage lung cancer. Lobectomy by VATS has many advantages over conventional thoracotomy, such as shorter recovery time, less postoperative pain, and faster resumption of a normal lifestyle. However, there is still much debate on the role of VATS in lobectomy for the treatment of lung cancer. Concerns regarding safety, the extent of mediastinal lymph node dissection, and long-term survival have made some surgeons apprehensive of its validity for lung cancer. In this paper, we review the development of thoracoscopy, the present status of VATS for early stage of non-small cell lung cancer (NSCLC), and comparison between VATS and open thoracotomy in the management of NSCLC.

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Tissue engineering of cartilage, tendon and bone
Hengyun SUN, Wei LIU, Guangdong ZHOU, Wenjie ZHANG, Lei CUI, Yilin CAO
Front Med. 2011, 5 (1): 61-69.  
https://doi.org/10.1007/s11684-011-0122-1

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Tissue engineering aims to produce a functional tissue replacement to repair defects. Tissue reconstruction is an essential step toward the clinical application of engineered tissues. Significant progress has recently been achieved in this field. In our laboratory, we focus on construction of cartilage, tendon and bone. The purpose of this review was to summarize the advances in the engineering of these three tissues, particularly focusing on tissue regeneration and defect repair in our laboratory. In cartilage engineering, articular cartilage was reconstructed and defects were repaired in animal models. More sophisticated tissues, such as cartilage in the ear and trachea, were reconstructed both in vitro and in vivo with specific shapes and sizes. Engineered tendon was generated in vitro and in vivo in many animal models with tenocytes or dermal fibroblasts in combination with appropriate mechanical loading. Cranial and limb bone defects were also successfully regenerated and repaired in large animals. Based on sophisticated animal studies, several clinical trials of engineered bone have been launched with promising preliminary results, displaying the high potential for clinical application.

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The role of protein kinase C epsilon in neural signal transduction and neurogenic diseases
Yuan CHEN, Qi TIAN
Front Med. 2011, 5 (1): 70-76.  
https://doi.org/10.1007/s11684-011-0119-9

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Protein kinase C epsilon (PKC ?) is one of major isoforms in novel PKC family. Although it has been extensively characterized in the past decade, the role of PKC ? in neuron is still not well understood. Advances in molecular biology have now removed significant barriers to the direct investigation of PKC ? functions in vivo, and PKC ? has been increasingly implicated in the neural biological functions and associated neurogenic diseases. Recent studies have provided important insights into the influence of PKC ? on cortical processing at both the single cell level and network level. These studies provide compelling evidence that PKC ? could regulate distinct aspects of neural signal transduction and suggest that the coordinated actions of a number of molecular signals contribute to the specification and differentiation of PKC ? signal pathway in the developing brain.

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MINI-REVIEW
Self-etching adhesives: possible new pulp capping agents to vital pulp therapy
Chun CUI, Xiu-Neng ZHOU, Wei-Min CHEN
Front Med. 2011, 5 (1): 77-79.  
https://doi.org/10.1007/s11684-010-0104-8

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Pulp capping is one of the solving for keeping vital pulp in the case of dentin caries, reversible pulpitis or traumatic pulp exposure. The presence of bacteria on the cavity walls or in the pulp was the major factor that leads to the failure of pulp capping. Traditional pulp capping agent, calcium hydroxide, may not prevent microleakage. Self-etching system is a newly developed adhesive system, which could provide less microleakage and would not break down or dissolve, preventing the oral fluids and bacteria from the pulp along the cavity wall. This may reduce such clinical problems as postoperative sensitivity, secondary caries and marginal discoloration. Researches showed that some kinds of self-etching adhesives induced the mild to moderate inflammatory pulp response, with negative bacterial staining. Inclusion of antibacterial components into self-etching system, such as 12- methacryloyloxydodecylpyridinium bromide (MDPB) may inhibit bacteria and provide better clinical effects. It is speculated that using the self-etching adhesive system containing the antibacterial agent, such as MDPB, to the dental pulp directly or indirectly, may inhibit bacteria after the placement of restoration as well as residual bacteria in the cavity.

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RESEARCH ARTICLE
Successful kidney transplantation in highly sensitized patients
Weijie ZHANG, Dong CHEN, Zhishui CHEN, Fanjun ZENG, Changsheng MING, Zhengbin LIN, Ping ZHOU, Gang CHEN, Xiaoping CHEN
Front Med. 2011, 5 (1): 80-85.  
https://doi.org/10.1007/s11684-011-0115-0

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Highly sensitized patients experience an increased number of rejection episodes and have poorer graft survival rates; hence, sensitization is a significant barrier to both access to and the success of organ transplantation. This study reports our experience in kidney transplantation in highly sensitized patients. Fourteen patients with sensitization or high levels of panel-reactive antibodies (PRA) were studied. All patients were desensitized with pre-transplant intravenous immunoglobulin (IVIG)/plasmapheresis (PP) with or without rituximab and thymoglobulin induction therapy, combined with a Prograf/MMF/Pred immunosuppressive regimen. Of 14 patients, 10 showed good graft functions without acute rejection (AR) episodes. Acute cellular rejection in two patients was reversed by methylprednisolone. Two patients underwent antibody-mediated rejection; one was treated with PP/IVIG successfully, whereas the other lost graft functions due to the de novo production of donor-specific antibodies (DSA). Graft functions were stable, and there were no AR episodes in other patients. Conclusively, desensitization using PP/IVIG with or without rituximab increases the likelihood of successful live-donor kidney transplantation in sensitized recipients.

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Overexpression of netrin-1 improves neurological outcomes in mice following transient middle cerebral artery occlusion
Haiyan LU, Yongting WANG, Falei YUAN, Jianrong LIU, Lili ZENG, Guo-Yuan YANG
Front Med. 2011, 5 (1): 86-93.  
https://doi.org/10.1007/s11684-011-0118-x

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Netrin-1 (NT-1) is one of the axon-guiding molecules that are critical for neuronal development. Because of its structural homology to the endothelial mitogens, NT-1 may have similar effects on vascular network formation. NT-1 was shown to be able to stimulate the proliferation and migration of human cerebral endothelial cells in vitro and also promote focal neovascularization in adult brain in vivo. In the present study, we reported the delivery of NT-1 using an adeno-associated virus (AAV) vector (AAV-NT-1) into mouse brain followed by transient middle cerebral artery occlusion (tMCAO). We found that AAV vectors did not elicit a detectable inflammatory response, cell loss or neuronal damage after brain transduction. The level of NT-1 was increased in the AAV-NT-1-transduced tMCAO mice compared with the control mice. Furthermore, the neurobehavioral outcomes were significantly improved in AAV-NT-1-transduced mice compared with the control animals (P<0.05) 7 days after tMCAO. Our data suggests that NT-1 plays a neuronal function recovery role in ischemic brain and that NT-1 gene transfer might present a valuable approach to treat brain ischemic disorders.

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Transplantation of placenta-derived mesenchymal stem cells in type 2 diabetes: a pilot study
Ranhua JIANG, Zhibo HAN, Guangsheng ZHUO, Xiaodan QU, Xue LI, Xin WANG, Yuankang SHAO, Shimin YANG, Zhong Chao HAN
Front Med. 2011, 5 (1): 94-100.  
https://doi.org/10.1007/s11684-011-0116-z

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Mesenchymal stem cells (MSC) have been used in clinical trials for severe diabetes, a chronic disease with high morbidity and mortality. Bone marrow is the traditional source of human MSC, but human term placenta appears to be an alternative and more readily available source. Here, the therapeutic effect of human placenta-derived MSC (PD-MSC) was studied in type 2 diabetes patients with longer duration, islet cell dysfunction, high insulin doses as well as poor glycemic control in order to evaluate the safety, efficacy and feasibility of PD-MSC treatment in type 2 diabetes (T2D). Ten patients with T2D received three intravenous infusions of PDSC, with one month interval of infusion. The total number of PDSC for each patient was (1.22–1.51) × 106/kg, with an average of 1.35 × 106/kg. All of the patients were followed up after therapy for at least 3 months. A daily mean dose of insulin used in 10 patients was decreased from 63.7?±?18.7 to 34.7?±?13.4 IU (P<0.01), and the C-peptide level was increased from 4.1?±?3.7 ng/mL to 5.6?±?3.8 ng/mL (P<0.05) respectively after therapy. In 4 of 10 responders their insulin doses reduced more than 50% after infusion. The mean levels of insulin and C-peptide at each time point in a total of 10 patients was higher after treatment (P<0.05). No fever, chills, liver damage and other side effects were reported. The renal function and cardiac function were improved after infusion. The results obtained from this pilot clinical trial indicate that transplantation of PD-MSC represents a simple, safe and effective therapeutic approach for T2D patients with islet cell dysfunction. Further large-scale, randomized and well-controlled clinical studies will be required to substantiate these observations.

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Downregulation effects of beta-elemene on the levels of plasma endotoxin, serum TNF-alpha, and hepatic CD14 expression in rats with liver fibrosis
Jianguo LIU, Zhe ZHANG, Jiechang GAO, Jiwen XIE, Lin YANG, Shenjun HU
Front Med. 2011, 5 (1): 101-105.  
https://doi.org/10.1007/s11684-011-0111-4

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It has been demonstrated that β-elemene could protect against carbon tetrachloride (CCl4)-induced liver fibrosis in our laboratory work, and the aim of this paper is to reveal the protective mechanisms of β-elemene. The hepatic fibrosis experimental model was induced by the hypodermical injection of CCl4 in Wistar male rats. β-elemene was intraperitoneally administered into rats for 8 weeks (0.1 mL/100 g bodyweight per day), and plasma endotoxin content was assayed by biochemistry. The serum TNF-α level was detected using radioactive immunity. CD14 expression in rat livers was measured by immunohistochemistry and Western blot. The results showed that β-elemene can downregulate the levels of plasma endotoxins, serum TNF-α, and hepatic CD14 expression in rats with liver fibrosis. β-elemene plays an important role in downregulating the lipopolysaccharide signal transduction pathway, a significant pathway in hepatic fibrosis development.

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A better way to do small-for-size liver transplantation in rats
Jiang LI, Yu HOU, Jing LIU, Bin LIU, Li LI
Front Med. 2011, 5 (1): 106-110.  
https://doi.org/10.1007/s11684-011-0113-2

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Establishing a model for small-for-size liver transplantation is the basis for this study of partial and living donor graft liver transplantation. This study aims to explore a simpler and more effective way of establishing a 30% small-for-size liver transplantation in rats. Sprague-Dawley rats were selected as the donors and recipients. Small-for-size orthotopic liver transplantation was performed using Kamada’s two-cuff method. The donor’s liver was flushed via the abdominal aorta and hepatectomy was performed in situ. The animals were divided into three groups depending on the graft selected, with 40 pairs of rats in each group. In group I, the median lobe of the liver was used as graft; in group II, the right half of the median lobe and the right lobe were used as graft; and in group III, the median and right lobes were used as graft. In groups I and II, the bodyweights of donors were the same as those of recipients; however, in group III the bodyweights of donors were 100–120 g less than those of the recipients. The duration needed for transplantation, the 7-day survival rates, and the technical complication rates were compared among these three groups. The time required for hepatectomy was shorter in group III compared with groups I and II (8.8?±?0.7 min vs. 11.5?±?1.1 min and 10.1?±?1.0 min, P = 0.001). The cold ischemia time for the grafts, the anhepatic times, and the transplantation times for the recipients were not significantly different among the three groups. Compared with groups I and II, the incidence of bleeding, bile leakage, and inferior vena caval strictures were significantly decreased in group III (P<0.05). No significant differences between the three groups were found based on other complications after the operation (P>0.05). Group III had better 7-day survival rates and longer median survival times but the differences were not statistically significant. The method of small for donor bodyweight using the median and right lobes for grafting may be a more effective and simpler way of establishing a 30% small-for-size liver transplantation in rats, as shown by the shorter hepatectomy time and the occurrence of fewer complications after the operation.

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17 articles