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Objective:To investigate the clinical characteristics, treatment and prognosis of newly-treated patients with primary central nervous system lymphoma (PCNSL).Methods:Clinical data of 117 newly-treated PCNSL patients who were admitted to the First Hospital of Jilin University, the Fifth Medical Center of Chinese PLA General Hospital, Harbin Medical University Cancer Hospital, and Cancer Hospital of Chinese Academy of Medical Sciences & Peking Union Medical College from August 2009 to February 2018 were retrospectively analyzed. The patients' age, sex, Eastern Cooperative Oncology Group (ECOG) physical status (PS) score, pathological type, involvement of deep brain tissue, number of lesions, cerebrospinal fluid protein concentration, International Extranodal Lymphoma Study Group (IELSG) score, Memorial Sloan Kettering Cancer Center (MSKCC) score, treatment strategy, and response after the first-line therapy were analyzed using univariate and multivariate Cox proportional hazards models to identify the independent influencing factors for progression-free survival (PFS) and overall survival (OS) of PCNSL patients. Kaplan-Meier method was used for survival analysis.Results:In 117 newly-treated PCNSL patients, 59 cases (50.4%) presented with increased intracranial pressure or focal neurological symptoms at diagnosis; there were 65 cases (55.6%) with single lesions and 52 cases (44.4%) with multiple lesions; 1 patient (0.9%) had lymphoma of T-cell origin, and 116 cases (99.1%) had diffuse large B-cell lymphoma (DLBCL). Among 95 evaluable patients, 41 patients (43.2%) achieved complete remission (CR), 20 patients (21.1%) achieved partial remission (PR), 16 patients (16.8%) achieved stable disease (SD), and 18 patients (18.9%) had progressive disease (PD). In 117 patients with median follow-up of 66.0 months (95% CI 57.9-74.1 months), the median PFS and OS were 17.4 months (95% CI 11.5-23.3 months) and 45.6 months (95% CI 20.1-71.1 months), respectively. The 2-, 3- and 5-year PFS rates were 41.2%, 28.6% and 19.3%, and OS rates were 63.7%, 52.4% and 46.3%, respectively. Univariate Cox regression analysis showed that baseline high-risk MSKCC score group was an adverse prognostic factor for PFS ( P = 0.037), and the first-line chemotherapy with ≥4 cycles of high-dose methotrexate (HDMTX), HDMTX in combination with rituximab, ≥4 cycles of rituximab in combination with HDMTX, and achieving CR or ≥PR after the first-line treatment reduced the risk of disease progression and prolonged the PFS time (all P <0.01); age >60 years old, ECOG-PS score of 2-4 points, elevated cerebrospinal fluid protein concentration, high-risk IELSG score, and high-risk MSKCC score were adverse prognostic factors for OS, and ≥4 cycles of HDMTX and achieving CR or ≥PR after the first-line treatment were favorable factors for OS. Multivariate Cox regression analysis verified that rituximab in combination with HDMTX (yes vs. no: HR = 0.349, 95% CI 0.133-0.912, P = 0.032) and achieving ≥PR after the first-line chemotherapy (yes vs. no: HR = 0.028, 95% CI 0.004-0.195, P < 0.001) were independent favorable factors for PFS; age >60 years old (>60 years old vs. ≤60 years old: HR = 10.878, 95% CI 1.807-65.488, P = 0.009) was independent unfavorable factor for OS, while ≥4 cycles of HDMTX treatment (≥4 cycles vs. <4 cycles: HR = 0.225, 95% CI 0.053-0.947, P = 0.042) was independent favorable factor for OS. Conclusions:The older the PCNSL patients at initial treatment, the worse the prognosis. Intensive and continuous treatment for achieving deeper remission may be the key for improving the outcome of PCNSL patients.
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To investigate the effect of INF-γ on the expression of programmed death ligand 1 (PD-L1), epithelial-mesenchymal transition (EMT) and the potential mechanism in breast cancer cell line MDA-MB-231, the cells were treated with different concentrations of INF-γ. The expressions of proteins, including PD-L1, cell-migration-related proteins (E-cadherin, N-cadherin and vimentin), ERK, p-ERK, Jak2, and p-Jak2 were detected by Western blotting analysis and immunofluorescent staining assay. Cell migration was studied through cell wound healing assay and transwell assay. IFN-γ could up-regulate the expressions of PD-L1 in MDA-MB-231 cells. The cell migration rate was significantly increased after adding IFN-γ. The expression levels of vimentin and N-cadherin were increased whereas the expression of E-cadherin was decreased after adding IFN-γ. The expression levels of ERK, p-ERK, Jak2 and p-Jak2 were significantly increased and this phenomenon was inhibited when adding ERK inhibitor U0126 or Jak2 inhibitor AG490. These results demonstrate that IFN-γ could up-regulate the expression of PD-L1, promote cell migration and transmission, and facilitate epithelial-mesenchymal transformation of breast cancer cells and this process may be related with ERK and Jak2-STAT signaling pathways.
Subject(s)
Humans , B7-H1 Antigen , Breast Neoplasms , Cell Line, Tumor , Cell Movement , Epithelial-Mesenchymal Transition , Extracellular Signal-Regulated MAP Kinases , Interferon-gamma , Janus Kinase 2 , STAT Transcription Factors , Signal TransductionABSTRACT
Neuropathic pain (NPP) is the main culprit among chronic pains affecting the normal life of patients. Procaine is a frequently-used local anesthesia with multiple efficacies in various diseases. However, its role in modulating NPP has not been reported yet. This study aims at uncovering the role of procaine in NPP. Rats were pretreated with procaine by intrathecal injection. Then NPP rat model was induced by sciatic nerve chronic compression injury (CCI) and behavior tests were performed to analyze the pain behaviors upon mechanical, thermal and cold stimulations. Spinal expression of Janus kinase 2 (JAK2) and signal transducer and activator of transcription 3 (STAT3) was detected by qRT-PCR and western blot. JAK2 was also overexpressed in procaine treated model rats for behavior tests. Results showed that procaine pretreatment improved the pain behaviors of model rats upon mechanical, thermal and cold stimulations, with the best effect occurring on the 15th day post model construction (p<0.05). Procaine also inhibited JAK2 and STAT3 expression in both mRNA (p<0.05) and protein levels. Overexpression of JAK2 increased STAT3 level and reversed the improvement effects of procaine in pain behaviors (p<0.01). These findings indicate that procaine is capable of attenuating NPP, suggesting procaine is a potential therapeutic strategy for treating NPP. Its role may be associated with the inhibition on JAK2/STAT3 signaling.
Subject(s)
Animals , Humans , Rats , Anesthesia, Local , Behavior Rating Scale , Blotting, Western , Chronic Pain , Injections, Spinal , Janus Kinase 2 , Models, Animal , Neuralgia , Procaine , RNA, Messenger , Sciatic Nerve , STAT3 Transcription FactorABSTRACT
Proteomics is an emerging discipline and has been widely used in a variety of fields despite of having very short history in comparison with other disciplines. In Chongqing Medical Univer-sity, the course contents were adjusted to fulfill the most effective integration of proteomics research with postgraduate training program for medical university. Diverse teaching was advocated here and af-ter-school communications were greatly encouraged in teaching. Traditional multimedia teaching plat-form remained the main teaching way and students were organized to visit the research platform as supplementing teaching way. The overall quality and effectiveness of teaching were effectively improved by successful implementation of the above initiatives.
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Teachers introduced the means of the scientific thinking and scientific research prac-tice in the curriculum of proteomics in order to train the postgraduates to joint the theory and the practical research work in the curriculum course. For example, to cultivate students to truly understand the 2-DE protein separation technique, teachers used the various proteomic profile obtained from our research to points out its problems and limitations based on the classical 2-DE, then compared the improved 2-DE protein separation chromatography with the classical 2-DE graphic and analyzed what is the problem and how to solve them in the practical work. To improve the ability of scientific thinking for postgraduates , teachers took the tumor as the teaching cases and asked the postgraduates to search the references of can-cer associated with their professional , to put forward the scientific problems based on carefully reading these references, to design their research project and to seek the answer to their issue. These new teaching methods were found to be beneficial in training scientific talents of medical postgraduates.
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Sample preparation and separation is a very crucial and complicated process in proteomics research.Based on the actual condition of university and students,this article explored the way to improve the teaching quality of sample preparation and separation in proteomics course for medical post-graduates aiming at cultivating and enhancing the students' scientific thought,making them have a better understanding of the rules,technologies,strategies in sample preparation and separation procedure.
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By evaluation of academic designed experiment performance in Bio-Analytic Chemistry from ten different evaluating indicators including literature search, experimental design, and experimental report and so on. The quantitative analysis results indicate the average is 87.8, the standard deviation is 5.0,the difficulty index is 0.88,the dipartite degree is 0.12 and the confidence coefficient of the assess is 0.9423. The designed experimental assessment can inspire the students’experimental goaheadism, cultivate their ability to analyze and solve problems,and promote their innovative consciousness and practice skills.
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The academic teaching quality and experimental teaching quality of sanitary chemistry will be improved,through enriching the teacher with specialized knowledge and cultivating the creative ability of thacher and updating the teaching methods.
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The present situation and problems in experiment teaching of analytical chemistry were explained,and innovation was explored and practiced in the faculty of laboratory medicine,including the opitimization of teaching contents,teaching methods and score system evaluation reformation.
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Beginning with the authors' experience in analytic-chemistry bilingual teaching,this article probes into some problems of analytic-chemistry in undergraduate education.And the authors give some beneficial suggestions in the teaching material construction,teachers training and teaching quality control.
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On the development of Bio-analytic chemistry curricula,to enhance the build- ing of teaching staff,improve the teaching content according to the developmental trend of model chemistry,adopt multiform methods to explore new teaching pattern,improve the teaching quality based on the manage,the course on Bio-analytic chemistry has became more systematized and standardized.