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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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2017 Vol. 5, No. 1
Published: 01 March 2017

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Liquid Biopsy in 2017: Circulating Tumor Cells and Circulating Tumor DNA in Precision Medicine Hot!

CAI Lei, PAN Ming-xin
Journal of International Translational Medicine, 2017, 5(1): 1-7 | doi:10.11910/2227-6394.2017.05.01.01
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With the popularization of molecular targeted drugs, precision medicine is gradually applied in cancer field. It makes cancer diagnosis and treatment more specific and targeted by combining genetic information, diagnosis and treatment of individual disease together. Therefore, to seek markers that can real-timely monitor cancer status is very important. As a key pathway of precision treatment, liquid biopsy is usually defined as the simple tests quickly done in blood samples or other body fluids. In cancer patients, the objective of those tests is to detect samples obtained from the tumors. As a non-invasive diagnostic technique, liquid biopsy takes circulating tumor cells (CTCs), circulating tumor DNA (ctDNA) and exosomes as the biomarkers of cancer diagnosis, which not only avoids surgical biopsy and aspiration biopsy, but also extracts the tumor samples repeatedly, consequently convenient for doctors to establish gene expression profiles. This article mainly reviewed CTCs and ctDNA monitoring technologies as well as their application in precision medicine.


Advances of Single-Cell Sequencing Technique in Tumors Hot!

FENG Ji-feng
Journal of International Translational Medicine, 2017, 5(1): 8-13 | doi:10.11910/2227-6394.2017.05.01.02
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With the completion of human genome project (HGP) and the international HapMap project as well as rapid development of high-throughput biochip technology, whole genomic sequencing-targeted analysis of genomic structures has been primarily finished. Application of single cell for the analysis of the whole genomics is not only economical in material collection, but more importantly, the cell will be more purified, and the laboratory results will be more accurate and reliable. Therefore, exploration and analysis of hereditary information of single tumor cells has become the dream of all researchers in the field of basic research of tumors. At present, single-cell sequencing (SCS) on malignancies has been widely used in the studies of pathogeneses of multiple malignancies, such as glioma, renal cancer and hematologic neoplasms, and in the studies of the metastatic mechanism of breast cancer by some researchers. This study mainly reviewed the SCS, the mechanisms and the methods of SCS in isolating tumor cells, and application of SCS technique in tumor-related basic research and clinical treatment.


Advances of Application of Transgenic Mice in Models with Breast Cancer

LI Ming-juan, JIANG Xiao-hong, GAO Guang-chun, HUANG Xuan
Journal of International Translational Medicine, 2017, 5(1): 14-18 | doi:10.11910/2227-6394.2017.05.01.03
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With the frequent cross fusion of medicine and molecular genetics, study on molecular aspects has become an important step in disclosing the pathogenesis of various diseases. The morbidity of breast cancer ranks the top one in malignancies in women, and is always the hot topic of researches. The establishment of transgenic animals has received more and more attentions because it can provide a more direct and effective platform to understand the pathogenesis of breast cancer as well as development of therapeutic agents. This study mainly emphasized on the application advances of transgenic animal techniques and transgenic mice in models with breast cancer.


Application of Anti-Müllerian Hormone in Diagnosis of Male Infertility

LIU Kang-sheng, YAO Hui, MAO Xiao-dong, TANG Xiao-yong, CHEN Ya-jun
Journal of International Translational Medicine, 2017, 5(1): 19-22 | doi:10.11910/2227-6394.2017.05.01.04
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Background: Early semen detection has become a major concern due to the increasing incidence of male infertility caused by deteriorated reproductive environmental pollution in the modern society. The purpose of this study was to evaluate the value of anti-Müllerian hormone (AMH) level in the diagnosis of male infertility.
Methods: According to fertility, the subjects undergoing health examination in Nanjing Obstetrics and Gynecology Hospital Affiliated to Nanjing Medical University were divided into infertile group (n=61) and fertile group (n=58). The levels of AMH in both seminal plasma and blood in two groups were detected using enzyme-linked immunosorbent assay (ELISA) method. The levels of serum follicle-stimulating hormone (FSH), luteinizing hormone (LH), testosterone (T) and prolactin (PRL) were all measured using electrochemiluminescence. The seminal AHM parameters in two groups were compared. The relationship between seminal AMH and other parameters, and the relationship between seminal AMH and serous AMH were analyzed in infertile group.
Results: In terms of AMH levels, sperm motility, class A sperm rate and sperm vitality, infertile group was markedly inferior to fertile group, and the difference was statistically significant (P<0.01). Pearson correlation results revealed that the level of seminal AMH was positively correlated with sperm motility, class A sperm rate and sperm viability (P<0.05), but had no correlation with the level of sexual hormones (P>0.05). The level of seminal AMH was significantly higher than that of serous AMH (P<0.01). Pearson correlation results revealed that there was no significant correlation between seminal AMH and serous AMH (r=0.026, P>0.05).
Conclusion: Seminal AMH can be an effective marker of insufficient sperms in infertile males, which may bring an optimized strategy to predict infertility when combined with conventional seminal parameters.


Effect of Azithromycin on Function of Peripheral Blood Dendritic Cells in Children with Bronchial Asthma

WANG Xuan, ZHANG Xi-rong, LI Gang
Journal of International Translational Medicine, 2017, 5(1): 23-28 | doi:10.11910/2227-6394.2017.05.01.05
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Objective: To observe the effect of azithromycin on the function of dendritic cells (DCs) originated from peripheral blood mononuclear cells (PBMCs) in children with bronchial asthma so as to explore the action mechanism of azithromycin in immunoregulation.
Methods: Totally 32 children with bronchial asthma were selected as observation group, and 30 healthy children through physical examination as control group. Under sterile condition, PBMCs were prepared using density gradient centrifugation, and DCs were induced by recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) and recombinant human interleukin-4 (rhIL-4) in vitro. Observation group was intervened by different concentrations of azithromycin (0.0, 0.1 and 10.0 mg/L), while control group didn’t receive any intervention. The expression rates of CD80, CD83 and CD86 on the surface of DCs were detected using flow cytometry, and the levels of IL-10 and IL-12 in the cultured supernate were measured by double antibody sandwich enzyme-linked immunosorbent assay (ELISA).
Results: The expression rate of CD86 was significantly higher, whereas the levels of IL-10 and IL-12 were markedly lower in observation group than in control group, and the differences were statistically significant (P<0.05 or P<0.01). In observation group, the level of IL12 was positively correlated with that of IL-10 (r=0.736, P<0.01), but no correlation was shown between the levels of IL-10 and IL-12 in control group (r=0.228, P>0.05). Significant difference was not shown by comparison to the expression rates of CD83, CD80 and CD86 on the surface of DCs intervened by azithromycin at 0.0, 0.1 and 10.0 mg/L (P>0.05). The levels of IL-10 at 0.1 and 10.0 mg/L were dramatically lower than that at 0.0 mg/L (P<0.01), and the level of IL-12 at 0.1 mg/L was notably lower than those at 0.0 and 10.0 mg/L (P<0.01).
Conclusion: DCs in children with bronchial asthma are imperfect, and are mainly marked by increase of CD86 expression and decrease of IL-10 and IL-12. Azithromycin does not impact the expression of CD80, CD86 and CD83 on the surface of DCs obviously, but can inhibit IL-10 and IL-12 secreted by DCs in children with bronchial asthma.


Clinical Outcomes of Percutaneous Transforaminal Endoscopic Discectomy Versus Fenestration Discectomy in Patients with Lumbar Disc Herniation

DING Zheng-mei, TAO Yong-qing
Journal of International Translational Medicine, 2017, 5(1): 29-33 | doi:10.11910/2227-6394.2017.05.01.06
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Background: Fenestration discectomy (FD) is a common treatment method for lumber disc herniation (LDH), with good effects obtained. Nevertheless, it also causes many complications, such as lumbar instability, lumbago and back pain. Percutaneous endoscopic lumbar discectomy (PTED) is a new minimally invasive treatment available for LDH with conservative therapy failure. At present, this technique has been carried out in China. The purpose of this study was to conduct a randomized prospective trial to compare the surgical outcomes of PTED and FD, explore the clinical application value of PTED, and discuss the operative manipulated skills of PTED.
Methods: Totally 100 patients with LDH were enrolled from March 2014 to December 2015 and randomly divided into PTED group and FD group, 50 cases in each group. FD group received FD including epidural anesthesia, unilateral fenestration decompression, removal of nucleus pulposus, and nerve root decompression and release, while FTED group received PTED including local anesthesia, endoscopic removal of herniated nucleus pulposus and nerve root decompression and release. Both groups were followed up postoperatively. The duration of operation, incision length, postoperative bed-rest and hospital stay were compared between two groups, and the visual analogue scale (VAS), Oswestry disability index (ODI), and therapeutic effects at the final follow-up time were recorded and compared between 2 groups.
Results: All patients completed the operation successfully. The surgical duration was similar between two groups (P>0.05). PTED group showed a less incision length and shorter postoperative bed-rest time and hospital stay than FD group (P<0.01). The VAS and ODI scores showed a significant decrease in both groups postoperatively when compared with operation before (P<0.05), but with no significant difference between two groups (P>0.05). Moreover, the excellent and good rate was higher in PTED group thanin FD group, with no statistical difference between them ((90.0% vs. 90.0%, Z=-1.113, P=0.266)).
Conclusion: Both FD and PTED are effective in the treatment of LDH. However, PTED is superior to FD due to smaller incision, shorter postoperative hospital stay, less affect on spinal instability and faster recovery, thus the long-term outcomes deserve to be further studied.


Can the Growth/Differentiation Factor-15 Be a Surrogate Target in Chronic Heart Failure Biomarker-Guided Therapy? Hot!

Alexander E. Berezin
Journal of International Translational Medicine, 2017, 5(1): 34-37 | doi:10.11910/2227-6394.2017.05.01.07
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Heart failure (HF) biomarker-guided therapy is a promising method, which directs to the improvement of clinical status, attenuation of admission/readmission to the hospital and reduction in mortality rate. Many biological markers, like inflammatory cytokines, are under consideration as a surrogate target for HF treatment, while there are known biomarkers with established predictive value, such as natriuretic peptides. However, discovery of new biomarkers reflecting various underlying mechanisms of HF and appearing to be surrogate targets for biomarker-guided therapy is fairly promising. Nowadays, growth/differentiation factor 15 (GDF-15) is suggested a target biomarker for HF treatment. Although elevated level of GDF-15 is associated with HF development, progression, and prognosis, there is no represented evidence regarding the direct comparison of this biomarker with other clinical risk predictors and biomarkers. Moreover, GDF-15 might serve as a contributor to endothelial progenitor cells (EPC) dysfunction by inducing EPC death/autophagy and limiting their response to angiopoetic and reparative effects. The short communication was discussed whether GDF-15 is good molecular target for HF biomarker-guided therapy.


Chemotherapy in Advanced Non-Small Cell Lung Cancer: Present and Future Hot!

Journal of International Translational Medicine, 2017, 5(1): 38-44 | doi:10.11910/2227-6394.2017.05.01.08
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Chemotherapy in the status of treating advanced Non-Small Cell Lung Cancer (NSCLC) was established in 1995. Many researches proved that chemotherapy could significantly improve overall survival (OS) and reduce the risk of death in patients with advanced NSCLC when compared with supportive care. Treatment options for advanced NSCLC are diverse, such as chemotherapy, molecular targeted therapy, immunotherapy, and their combination therapies. Those all bring about different benefits for patients. In this article, chemotherapy was mainly discussed, and it was concluded that pemetrexed continuation maintenance therapy is the preferred option in the treatment of patients advanced non-squamous NSCLC, and has a broader clinical application than bevacizumab. Chemotherapy (gemcitabine) is the main force for the treatment of patients with advanced squamous cell lung cancer. In addition, though chemotherapy combined with other regimens promise better therapeutic effect, there still remain many problems to be resolved. For example, how to select the right patients? What is the best route of drug administration, the optimal chemotherapy regimen, and the optimal chemotherapy dose? Therefore, the era of chemotherapy-free is far from coming, and no matter what treatment regimen is selected, chemotherapy is always an indispensable part of treating advanced NSCLC in the past, present, and future.


Interpretation of China Experts Consensus on the Diagnosis and Treatment of Brain Metastases of Lung Cancer (2017 Version)

HUANG Xin-en
Journal of International Translational Medicine, 2017, 5(1): 45-52 | doi:10.11910/2227-6394.2017.05.01.09
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Primary lung cancer (lung cancer for short) is one of the most common malignancies in China, with brain being one of the most common distant sites it spread to, which is termed brain metastases of lung cancer. The occurrence of brain metastases of lung cancer portends a poor prognosis, with mean survival time of only 1-2 months. However, the rapid development of radiotherapy technology and new therapies, like molecular targeted therapy, provides many therapeutic opportunities for brain metastases of advanced lung cancer. Combined application of surgery, radiotherapy and chemotherapy, to some extent, prolongs the survival and improve the quality of life (QoL) of patients. Now, treatment for brain metastases of lung cancer has become one of the hotspots in clinic. The purpose of this article was to interpret China Experts Consensus on the Diagnosis and Treatment of Brain Metastases of Lung Cancer (2017 Version) from the perspectives of diagnosis and treatment.

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