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Journal of International Translational Medicine
Journal of International Translational Medicine
JITM, ISSN 2227-6394
founded in 2012
Editor-in-chief:Feng Jifeng, China
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2016 Vol. 4, No. 4
Published: 30 December 2016

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Endoplasmic reticulum stress and apoptosis of tumor cells

LIU Kang-sheng, Liping, PENG Zheng-hang, SUN Er-hu, CHEN Ya-jun
Journal of International Translational Medicine, 2016, 4(4): 215-222 | doi:10.11910/2227-6394.2016.04.04.01
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Endoplasmic reticulum (ER) is the largest membrane-enclosed organelle in a cell, which is responsible for the synthesis, processing and modification of protein. ER is an important place of protein modifying, folding and assembling after protein translation of eukaryocyte. Some studies have shown that endoplasmic reticulum stress signaling pathways involve in death process of some kinds of cells. The ER environment about oxidation and high calcium concentration is destroyed, which will lead to the accumulation and aggregation of unfolded proteins and cause severe endoplasmic reticulum stress (ERS). ER transmembrane receptors detect the onset of ERS and initiate the unfolded protein response (UPR) to restore the normal ER function. The literatures on “endoplasmic reticulum stress/unfolded protein response/tumor cell apoptosis” as key words were retrieved in the full text database of PubMed and Web of Science from 1998 to 2016., Then 58 were selected in analysis at last. ERS triggers apoptosis through a variety of signaling pathways (the activation of Chop, Ire1-1-Jnk, and Caspase pathway). There is growing evidence that ER plays an important role in tumor cell diseases. The present reviews were focused on the discussion on the molecular mechanisms underlying UPR and the role of ERS in tumor cells.

Advances of Liver X Receptor Signaling Pathways in Prostate Cancer

LIU Yun, FENG Ji-feng
Journal of International Translational Medicine, 2016, 4(4): 223-228 | doi:10.11910/2227-6394.2016.04.04.02
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Liver X receptors (LXRs), a kind of ligand-activated transcription factors, belong to the nuclear receptor superfamily (NRS), and function as central transcriptional regulators for lipid homeostasis, for which agonists have been developed as potential drugs for cardiovascular diseases and metabolic syndromes. In sex hormone-dependent cancers, dysregulation of lipid metabolism has been manifested. Prostate cancer is the most frequent cancer in males in Europe and a leading cause of cancer deaths, with similar proportion in other developed countries. A lot of studies have confirmed that both LXR and its agonists may play some roles in the progression of prostate cancer, and LXR signaling pathways may have a close association with the development and progression of prostate cancer. Hence, to investigate the signaling pathways mediated by LXR and its agonists and their effects in prostate cancer is favorable to optimization of new treatment methods.

Developmental Status of Translational Medicine on Cerebral Stroke Hot!

WU Yun-chuan, GU Yi-huang, QIU Ya-lan, LI Xiao-yu, LIN Fa-cai
Journal of International Translational Medicine, 2016, 4(4): 229-234 | doi:10.11910/2227-6394.2016.04.04.03
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Translational medicine, as a new research theory and disciplinary branch, aims at the translation from bench to bedside. It can shorten the gap between basic scientific research and clinical treatment, and promote the highly efficient application of basic research results in clinical practice through bidirectional connection and feedback process between them. Cerebral stroke, as a common cerebrovascular circulatory disorder in clinic, is characterized by high morbidity, high disability rate and high mortality. After disease onset, patients are frequently complicated with severe functional disorders and sequelae, such as aphasia, paralysis, and partial or complete loss of self-care capacity, thus bringing about great burdens to the patients’ families and to the society. In China, there are more than 2 000 000 new cases with cerebral stroke annually, > 50% of whom are complicated with different-degree neurological functional decrease or deletion, and more than 1 000 000 die of cerebral stroke annually. Therefore, cerebral stroke is also an important concern in translational medicine study. In recent years, International Stroke Conference has emphasized the necessity of translational medicine research, and the bidirectional translation of bench to bedside (B2B) is of great significance in guiding the development of depth and width of translational medicine on stroke. This study mainly reviewed the advances of translational medicine at home and abroad and its significance in guiding the clinical treatment of cerebral stroke. 

Minimally-Invasive Precision Treatment of Tumors: Current Status and Future Prospects

LI Wei, LIU Jing-xing
Journal of International Translational Medicine, 2016, 4(4): 235-241 | doi:10.11910/2227-6394.2016.04.04.04
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Malignant tumors are common diseases that severely threaten people’s health, and also major diseases that lead to disability and early death. The treatment methods for malignant tumors worldwide mainly include surgery, radiotherapy, chemotherapy, etc., but the function of important organs may be damaged when the efficacy is obtained after application of extended radical resection, extended field irradiation and large-dose impact chemotherapy. With medical development, minimally-invasive techniques have been widely used in the treatment of tumors, and their application provides a new direction for tumor treatment. At present, the treatment mode of tumors has gradually entered into an era of pursuing minimal invasion and precision. The minimal invasion, precision and high efficacy are always proposed in the treatment of tumors, so open surgeries or some therapies that result in severe adverse reactions will be replaced gradually, or could be used as the alternatives. In this article, the characteristics and the latest research results of some major techniques were briefly reviewed in the minimally-invasive field.

Advance of Artificial Liver Support System in Hepatic Failure

Journal of International Translational Medicine, 2016, 4(4): 242-247 | doi:10.11910/2227-6394.2016.04.04.05
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The liver, as a complex organ in human body, has the functions of synthesis, detoxification, metabolism, secretion, biotransformation and immune defense. Hepatic failure has become a life-threatening disease, with a high morbidity and mortality. As a bridge of liver transplantation, artificial liver support system (ALSS) which is regarded as one of effective treatment for liver failure has already been widely applied in the clinical treatment to promote the survival and recovery of patients with hepatic failure. According to the properties of ALSS, ALSS is classified into non-bioartificial liver support system (NBALSS), bioartificial liver support system (BALSS) and hybrid artificial liver support system (HALSS). This paper aimed to review the functions, clinical application status, existing problems, and development of ALSS.

Preparation and Characterization of Nano-Sized TiO2@Chitosan for Bone Tissue Engineering Hot!

JIANG Lei, ZHOU Jie,ZHAO Yun-fu, WEI Chang-zhen, HUANG Jian-tao
Journal of International Translational Medicine, 2016, 4(4): 248-257 | doi:10.11910/2227-6394.2016.04.04.06
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Background: With the development of genetic engineering, it is urgent to find a vector with high transfection efficiency and good biocompatibility for genes. We considered combining nano-TiO2 with chitosan (CTS) in order to tap their respective advantages to make a better new nanoparticle as gene vector.
Methods: TiO2@CTS was prepared using microemulsion method. The physicochemical property of TiO2@CTS was measured by transmission electron microscopy (TEM) and zeta potential. The safety and influence on MC3T3-E1 cells were detected by methyl thiazolyl tetrazolium (MTT), blood compatibility assay and flow cytometry.
Results: TiO2@CTS was well prepared and it was safe to cells under concentration tests. TiO2@CTS particles had a fuzzy boundary with a particle size remaining in 20-30 nm. Besides, the results also showed that TiO2@CTS did better in cellular uptake than TiO2 at 2 h and 24 h, and had good biocompatibility. MTT assay proved that the MC3T3 cells remained good growth when treated with different concentrations of TiO2@CTS (2.5, 5, 10, 20, 40 and 80 μg/mL). Moreover, transfection assay in vitro and electrophoretic mobility shift assay illustrated the high transfection efficiency of TiO2@CTS.
Conclusion: TiO2@CTS is a good choice to gene transfection, with good biocompatibility, and it also provides a new thought for the application of nanotechnology in the field of aveolar bone graft material.

Safety of Regional 8-MHz Radiofrequency Capacitive Hyperthermia Combined with Magnetic Cationic Liposomes in Patients with Castration-Resistant Prostate Cancer: A Phase I Clinical Study Hot!

Noriyasu Kawai, Takeshi Kobayashi, Daichi Kobayashi, Kaname Tsutsumiuchi, Keitaro Iida, Toshiki Etani, Taku Naiki, Ryosuke Ando, Kentaro Mizuno, Atsushi Okada, Keiichi Tozawa, Takahiro Yasui
Journal of International Translational Medicine, 2016, 4(4): 258-267 | doi:10.11910/2227-6394.2016.04.04.07
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Background: Magnetites (iron oxide nanoparticles in Fe3O4) coated with positively charged liposomes are called as magnetic cationic liposomes (MCLs). MCLs used in an 8-MHz radiofrequency (RF) capacitive heating device can increase the temperature of a specific site to up to 45℃. The aim of this study was to evaluate the safety of regional 8-MHz RF capacitive hyperthermia combined with MCL in patients with castration-resistant prostate cancer (CRPC). 
Materials and methods: Three CRPC patients resistant to standard cancer therapy were enrolled in this study. The patients were injected with 0.5 mL MCL containing Fe (30 mg/mL) into the prostate, followed by application of the heat using an 8-MHz RF capacitive heating device. The primary end point was to evaluate the presence, or absence, as well as the degree of adverse events. The secondary end point was to obtain preliminary efficacy data. 
Results: The temperature of the tumor was increased by more than 2℃ following MCL injection when compared with the 8-MHz RF treatment alone. No severe adverse events were noted in the prostate, rectum, or the bladder. After treatment, both levels of prostate-specific antigen (PSA) and interleukin-6 (IL-6) in the tissue were increased in three patients by varying degrees. 
Conclusion: The present study confirms the safety of regional 8-MHz RF capacitive hyperthermia combined with MCL.

Relationship Between Cervical Disc Herniation and Posterior Longitudinal Ligament in Intra-operative Microscope-Guided 468 ACDF Hot!

LI Ze-qing, TAN Jun, LI Li-jun, YANG Ming-jie, PAN Jie
Journal of International Translational Medicine, 2016, 4(4): 268-273 | doi:10.11910/2227-6394.2016.04.04.08
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Objective: To observe the relationship between cervical disc herniation (CDH) and posterior longitudinal ligament (PLL) under microscope-guided anterior cervical decompression and fusion (ACFD), with intention to provide the basis for PLL surgery resection.
Methods: Totally 325 patients with CDH (468 levels) were performed with microscope-guided ACFD. During the procedure, integrity of annulus, PLL, and dural sac were observed. Meanwhile, the position of the protruded mass was recorded. The actual exploratory results under microscope were documented and compared with preoperative magnetic resonance imaging (MRI) presentation.
Results: According to disc-posterior anatomic layers and findings under the intraoperative microscope, 468 levels of CDH were classified into five sites. Site I: disc with tearing annulus but intact outmost layer (in 47 levels); Site Ⅱ: ruptured annulus with intact PLL (in 202 levels);Site Ⅲ: herniated mass within or through PLL (in 107 levels); Site Ⅳ: free and sequestered mass posterior to PLL (in 105 levels); Site V: intradural CDH (in 7 levels).
Conclusion: This observation of CDH reveals the chronic and dynamic progress of the disease. Though MRI is considered a powerful and sensitive technique for the assessment of CDH, it may not provide the proof for the relationship between CDH and PLL. To ensure the complete anterior decompression, the PLL should be resected routinely to explore if there is free disc mass under PLL.

Translational Research on Traditional Chinese Medicine in Patients with Hepatitis B Virus-Related Liver Cirrhosis via Treatment with Nucleotide Analogues Hot!

ZHOU Xiao-ling, CHEN Qiao, LI Can, LIU Shan, LI Ze-peng, LIU Ying, YU Jing-fang, QIN Feng-chuan, ZHANG Yue
Journal of International Translational Medicine, 2016, 4(4): 274-280 | doi:10.11910/2227-6394.2016.04.04.09
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Objective: To observe the clinical effects of different courses of HBV Negative Conversion Powder in the treatment of patients with Hepatitis B virus (HBV)-related liver cirrhosis via treatment with nucleotide analogues, as so to provide guidance for standardized use of this drug. 
Methods: A total of 172 patients with HBV-related liver cirrhosis who showed HBV DNA negative conversion via treatment with nucleotide analogues were enrolled and randomly divided into four groups (groups A, B, C and D, 43 cases in each group). Patients in four groups were treated with original nucleotide analogues, based on which, group A was added with HBV Negative Conversion Powder for 12 months, group B with HBV Negative Conversion Powder for 9 months, group C with HBV Negative Conversion Powder for 6 months, but group D without HBV Negative Conversion Powder. The total courses of treatment were 12 months for all groups. 
Results: The liver function, four indexes of liver fibrosis, the condition of abdominal ultrasonogram and liver stiffness in groups A, B and C were significantly improved when compared with group D treated with original nucleoside analog alone (P<0.05), and the therapeutic effect was best in group A (P<0.01). Additionally, the HBeAg negative conversion rates of groups A and B were higher than that of group D, and the difference was significant (P<0.05).   
Conclusion: Chinese herba preparation HBV Negative Conversion Powder, when combined with original nucleoside analogs, can improve the liver function and liver fibrosis, and inhibit the replication of HBV and improve the HBeAg negative conversion rate of patients with HBV-related liver cirrhosis who were treated with nucleotide analogues. Moreover, the use of HBV Negative Conversion Powder for 12 months shows the best clinical therapeutic effects. This study promotes the transformation of scientific research achievements and provides a basis for guiding the standardized use of this preparation.

Study on the Correlation of Fibroblast Growth Factor 21 Level with the Obesity, Lipid Metabolism and Insulin Resistance in Patients with Non-Alcoholic Fatty Liver Disease Hot!

XIAO Jian-xin, CHEN Lei
Journal of International Translational Medicine, 2016, 4(4): 281-286 | doi:10.11910/2227-6394.2016.04.04.10
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Objective: To analyze the correlation of fibroblast growth factor 21 (FGF21) level with the obesity, lipid metabolism and insulin resistance in patients with non-alcoholic fatty liver disease (NAFLD).
Methods: According to the presence of type 2 diabetes mellitus (T2DM), 156 patients with NAFLD were assigned into NAFLD+T2DM group (n=83) and NAFLD group (n=73). Meanwhile, 75 healthy people who had physical examinations were collected as control group. The physiological and biochemical indexes, insulin resistance parameters as well as FGF21 levels were all compared among three groups. The correlation of FGF21 level with each clinical index was analyzed in patients with NAFLD, and multiple linear regression analysis was also conducted for the analysis of influencing factors of FGF21 level.
Results: The proportion of obesity, waist-to-hip ratio (WHR), body mass index (BMI), levels of total cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterol (LDL-C), free fatty acid (FFA), FGF21, fasting insulin (FINS) and homeostasis model assessment-insulin resistance (HAMO-IR) were all significantly higher, while insulin sensitivity index (ISI) and level of high
density lipoprotein cholesterol (HDL-C) was conspicuously lower in NAFLD+T2DM group and NAFLD group than in control group (P<0.01). WHR, BMI and ISI were lower, whereas the levels of TG, FFA, fasting plasma glucose (FPG), FINS and HAMO-IR were higher in NAFLD+T2DM than in NAFLD group, and the significant differences were shown (P<0.05 or P<0.01). In patients with NAFLD, the level of FGF21 was positively correlated with BMI, WHR, HOMA-IR, TG and FFA (r=0.258, 0.336, 0.327, 0.304, 0.312, P all <0.05), but negatively with ISI and HDL-C (r=-
0.224, -0.279, P all <0.05). Multiple linear regression analysis displayed that WHR, HOMA-IR and TG predominantly affected the level of plasma FGF21 in patients with NAFLD, in which the effect of WHR was the most significant.
Conclusion: The level of FGF21 increases dramatically in patients with NAFLD, and is closely associated with the obesity, lipid metabolism and insulin resistance.


Interpretation of NCCN Guideline: Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (Version 1, 2017)

XIA Lei, TANG Yan, XU Xin-yu, ZHU Miao-lin
Journal of International Translational Medicine, 2016, 4(4): 287-292 | doi:10.11910/2227-6394.2016.04.04.11
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Chronic lymphocytic leukemia (CLL) is a kind of chronic lymphocyte proliferative disease with corresponding clinical symptoms caused by the accumulation of mature B lymphocytes in peripheral blood, bone marrow and lymphatic tissues. In recent years, great achievements have been reached on the basic research, new prognostic markers, diagnostic criteria and therapeutic methods in CLL. This study mainly interpreted the corresponding diagnosis and treatment of CLL in NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®): Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (Version 1, 2017).
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