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Objective:To investigate whether radiotherapy should be delivered before the application of immune checkpoint inhibitor PD-1 in patients with advanced non-small cell lung cancer (NSCLC) and evaluate the effect of previous radiotherapy on the efficacy and pulmonary toxicity of PD-1 inhibitor.Methods:Clinical data of patients with stage Ⅳ NSCLC who received immunotherapy in Henan Cancer Hospital from March 2015 to September 2019 were retrospectively analyzed. The baseline data of patients, the status of radiotherapy and immunotherapy and the pulmonary toxicity were collected. According to whether radiotherapy was given before PD-1 inhibitor application, all patients were divided into the previous radiotherapy and non-radiotherapy groups. Survival analysis was performed by Kaplan- Meier method. Results:A total of 90 patients were enrolled including 39 cases in the previous radiotherapy group and 51 cases in the non-radiotherapy group. The median follow-up time was 22.9 months. The median progression-free survival (mPFS) in the previous radiotherapy group was 7.5 months (95% CI 5.4-9.5 months), significantly longer compared with 4.1 months (95% CI 3.1-5.1 months) in the non-radiotherapy group ( P=0.003). The median overall survival (mOS) significantly differed between two groups[15.2 months (95% CI 12.3-18.1 months) vs. 9.3 months (95% CI 6.1-12.5 months)]( P=0.040). The incidence of pulmonary toxicity showed no significant difference between two groups ( P=0.154). Conclusions:Patients with stage Ⅳ NSCLC patients in the previous radiotherapy group obtain significantly better mPFS and mOS and similar pulmonary toxicity compared with their counterparts in the non-radiotherapy group. Nevertheless, the findings remain to be validated by subsequent investigations with larger sample size.
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Objective:To evaluate the value and identify the prognosic factors of postoperative radiotherapy (PORT) in completely resected stage Ⅲ(pN 2) lung adenocarcinoma patients with epidermal growth factor receptor (EGFR) wild-type who received adjuvant chemotherapy. Methods:Clinical data of 172 patients with stage Ⅲ(pN 2) EGFR wild-type lung adenocarcinoma who underwent radical resection and adjuvant chemotherapy from 2009 to 2016 were retrospectively analyzed. All patients received platinum-based adjuvant chemotherapy combining two drugs for>4 cycles, and divided into the PORT group and the non-PORT group. The survival rate was calculated by Kaplan- Meier method and log-rank test, and multivariate prognostic analysis was performed by Cox’s regression model. Results:Among 172 patients, the median overall survival (OS), 3-year and 5-year OS rates were 40 months, 55.9% and 28.3%, respectively. The median disease-free survival (DFS), 3-year and 5-year DFS rates were 17 months, 24.5% and 13.0%, respectively. DFS was significantly improved in the PORT group (29 months vs. 13 months, P=0.001), whereas OS did not significantly differ between two groups (51 months vs. 38 months, P=0.151). In subgroup analysis, DFS of patients with multistation N 2 or the number of N 2 metastases of≥3 or skip N 2 in the PORT group was significantly longer ( P<0.05), whereas PORT exerted no significant effect on OS ( P>0.05). Conclusions:For patients with completely resected stage Ⅲ(N 2) EGFR wild-type lung adenocarcinoma receiving adjuvant chemotherapy, PORT might increase DFS and have a trend toward longer OS. However, these findings remain to be validated by large sample size investigations.
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BACKGROUND: A number of clinical trials addressing olfactory ensheathing cells for the treatment of chronic spinal cord injury have been conducted in the world, but the efficacy and safety are still controversial. OBJECTIVE: To evaluate the safety and efficacy of olfactory ensheathing cell transplantation for chronic spinal cord injury, and to further compare its short-and long-term efficacy. METHODS: PubMed, Cochrane Library, EMBASE, CNKI and WanFang databases were searched at July 23, 2018 for retrieval of clinical trials addressing olfactory ensheathing cells in the treatment of chronic spinal cord injury. Types and cases of adverse events during the safety trial should be recorded in detail. In the enrolled studies, American Spinal Injury Association scale was used to assess the motor, light touch, and pinprick scores of spinal cord injury patients before and after cell transplantation. The follow-up time was recorded. Systematic evaluation of efficacy data was performed using Review Manager 5.3. RESULTS AND CONCLUSION: Both short-and long-term follow-up data showed that the neurological function of patients was significantly improved after olfactory ensheathing cell transplantation (P < 0.05), and the results were homogeneous (I2 < 50% and P> 0.1). However, the long-term efficacy was not as good as the short-term efficacy, which may be related to chronic rejection and olfactory ensheathing cell survival. The overall adverse event rate was 8.99%, and no complications associated with olfactory ensheathing cells occurred. These findings show that olfactory ensheathing cell transplantation is effective and safe in the treatment of chronic spinal cord injury, but it is still necessary to explore more minimally invasive approaches to reduce surgical complications. In addition, a large number of high-quality experiments and clinical trials are warranted to confirm factors affecting the long-term efficacy of olfactory ensheathing cell transplantation.
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BACKGROUND: A number of clinical trials addressing olfactory ensheathing cells for the treatment of chronic spinal cord injury have been conducted in the world, but the efficacy and safety are still controversial. OBJECTIVE: To evaluate the safety and efficacy of olfactory ensheathing cell transplantation for chronic spinal cord injury, and to further compare its short-and long-term efficacy. METHODS: PubMed, Cochrane Library, EMBASE, CNKI and WanFang databases were searched at July 23, 2018 for retrieval of clinical trials addressing olfactory ensheathing cells in the treatment of chronic spinal cord injury. Types and cases of adverse events during the safety trial should be recorded in detail. In the enrolled studies, American Spinal Injury Association scale was used to assess the motor, light touch, and pinprick scores of spinal cord injury patients before and after cell transplantation. The follow-up time was recorded. Systematic evaluation of efficacy data was performed using Review Manager 5.3. RESULTS AND CONCLUSION: Both short-and long-term follow-up data showed that the neurological function of patients was significantly improved after olfactory ensheathing cell transplantation (P < 0.05) , and the results were homogeneous (I2 < 50% and P> 0.1). However, the long-term efficacy was not as good as the short-term efficacy, which may be related to chronic rejection and olfactory ensheathing cell survival. The overall adverse event rate was 8.99%, and no complications associated with olfactory ensheathing cells occurred. These findings show that olfactory ensheathing cell transplantation is effective and safe in the treatment of chronic spinal cord injury, but it is still necessary to explore more minimally invasive approaches to reduce surgical complications. In addition, a large number of high-quality experiments and clinical trials are warranted to confirm factors affecting the long-term efficacy of olfactory ensheathing cell transplantation.
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Objective:To explore characteristics of family function in patients with major depressive disorder (MDD),and to evaluate relationships between family function and prognosis of major depressive episode (MDE).Methods:Forty-six patients with MDD were recruited in the outpatient or inpatient departments of Wuhan Mental Health Center from September 1,2014 to August 31,2015.At the baseline,the patients and their co-resident family members were interviewed for psychiatric screening and diagnosis,and the family function of each patient's family was assessed by Family Assessment Device (FAD).After clinic service or hospitalization,the patients were followed up by telephone until they recovered from the MDE (within 12 months since the follow-up) or for 12 months if they had not achieved remission.Forty-two mentally healthy subjects,with no family members diagnosis for psychiatric diseases,and matched with MDD patients for age,sex,number of children,family roleand socioeconomic status,were recruited from a community.The family function of the MDD families and the controls were compared by independent sample-T test,and the relationship between family function and duration of the MDE was analyzed by Pearson's correlation.Results:MDD families exhibited higher FAD scores in 5 dimensions than control families except for affective involvement and behavior control (P<0.01).Patients with relatively good family function showed significantly shorter duration of MDE and higher proportion of remission within 6 months since the follow-up (P<0.01 and P<0.05).All the dimensions of FAD demonstrated significant positive correlation with the duration of MDE except for the behavior control.Conclusion:Families with MDD patients show impairments in multiple dimensions of family function,and the family functions of MDD patients are correlated with the prognosis of MDE.Improvement of family function may contribute to better prognosis of MDD.
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Objective To develop a simple method of determination of sorafenib in serum by reversed-phase high performance liquid chromatography (RP-HPLC) and to explore its application in sorafenib therapeutic drug monitoring (TDM).Methods Sorafenib extracted by ethyl ether-petroleum (9∶1) with internal standard of erlotinib from serum was wiped off in 60 ℃ water bath.Sorafenib was redissolved by mobile buffer and analyzed by 40 μl.Chromatographic column was Symmetry Rp18 (5 μm,4.6 mm×250 mm,waters) column in normal temperature.The mobile buffer was 28 mmol/L acetate buffer (pH 5.8)-acetonitrile (37∶63).Sorafenib and erlotinib were detected in 249 nm and 335 nm,respectively.Results The concentration range of sorafenib was 0.50-20.00 μg/ml (r =0.9999).The within-day and between-day accuracies of sorafenib were less than 4.77 % and 8.79 %,respectively.The average recovery rate was 98.48 %.Sorafenib was stable in serum or after extraction.The concentrations of sorafenib in two patients were detected.Conclusion Detection of sorafenib in serum by RP-HPLC is simple and accurate,which is available to determine sorafenib in serum.The TDM of sorafenib has clinical significance.
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Objective To analyze the influence of peptidimer-c on the gene expression profiling of K562 cells and investigate the mechanism of peptidimer-c inducing the apoptosis and inhibiting proliferation of K562cells.Methods Trypan blue staining technique was performed for counting the number of living K562 cells treated with peptidimer-c.The ultrastructure changes of K562 cells treated with peptidimer-c was observed under transmission electron microscope.The Human U133 Plus 3.0 gene chips were used to detect the differentially expressed genes of K562 cells treated with peptidimer-c.Reverse transcription PCR was conducted to confirm some genes identified by gene chips.Results Peptidimer-c could induce the apoptosis and inhibit the proliferation of K562 cells.Peptidimer-c caused widely changes of the gene expression profiles of K562 cells.The chip data suggested that there were 529 differentially expressed genes,of which 455 genes were up-regulated and 74 genes were down-regulated.The relevant apoptotic genes were down-regulated markedly,including JUN,AXUD1,TNFRSF10B,etc.Fifteen of the differentially expressed genes were detected by RT-PCR,which was consistent with the chip data.Conclusion Peptidimer-c may induce aooptosis of K562 cells by activating the TNF/TNFR family and the JUN family.
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Objective To analyze the characteristic of serum proteins in non-small cell lung cancer (NSCLC) patients, establish serum markers pattern for the diagnosis of NSCLC. Methods Surface enhanced laser desorption ionization time of flight mass spectormetry ( SELDI-TOF-MS) technology was used to analyze serum samples. Bio-marker Pattern Software (BPS) was used to detect the protein peaks. Results Sixteen significantly different pro-tein peaks were found in serum samples in NSCLC patients and healthy controls. Eight up-regulated protein peaks and eight down-regulated protein peaks ( P < 0. 001 ) were identified in serum samples of NSCLC patients. Three up-regulated protein peaks(P <0. 05) were identified in serum samples of patients of NSCLC with smoking history. Two up-regulated protein peaks(P <0. 01) were identified in serum samples of patients of squamous carcinoma comparing with adenocarcinoma. No significantly different protein peak was found in serum samples of NSCLC patients at different clinical stages . Conclusion SELDI - TOF - MS technology can identify different protein peaks and so function as a diagnostic tool with high sensitivity and specificity.
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Objective To screen serum biomarkers in patients with hepatocelhlar carcinoma by using surface-enhanced laser desorption and ionization time-of-flight mass spectrometry(SELDI-TOF-MS)technique and to evaluate its clinical implication in the patients whose alpha-fetoprotein were negative in the sera. Methods Proteomic spectra were generated by mass spectroscopy in 112 cases, including 57 cases AFP-negative hepatocellular carcinoma,and 55 cases of healthy control. The consequence was analyzed and the characteristic preteomic peaks was selected by using Biomarker Wizard. Results Seven low expressed potential biomarker were indentified with the mass-to-charge ratio of 4.2×103, 4.1×103, 6.7×103, 5.7×103, 6.5×103, 6.9×103, 5.8×103. The sensitivity for diagnosing hepatic cancer were 88.23 % and specificity was 92.31%. These peaks were not correlated with age, sex, tumor mass size, pathology grading and cirrhosis in hepatocellular carcinoma. Conclusion SELDI-TOF-MS offers a unique platform for the proteomic detection of hepatocellular carcinoma.It also offers an auxiliary diagnosis method to the patients whose alpha-fetoprotein are negative in the serum.
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BACKGROUND: Hematopoietic stem cells have an ability of multi-directional differentiation and can be differentiated into megakayocytes in the presence of suitable hematopoietic growth factors and lineage special growth factors.Inducing of CD34+ stem cells to megakaryocytes in vitro involves many changes in gene expression, especially the signal transduction genes.OBJECTIVE: To study the expression of signal transduction genes after differentiation from stem cells into megakaryocytes.DESIGN: Open experiment.SETTING: Department of Tumor Immunology, Fujian Provincial Tumor Hospital.MATERIALS: 60-145 mL of cord blood was collected from normal labor fetuses under sterile conditions by using the blood-bag collective method. Patients and their relatives provided the confirmed consent. Reagents and equipments were detailed as follows: VarioMACS segregation apparatus, CD34+ Isolation Kit, SCGM serum-free medium, CD monoclonal antibodies, cytokines, human genome Oligo Set Version 2.1 from the CapitalBio Corporation, and LuxScan 10K/A bi-passage laser scanning apparatus. The researchers obtained consent from the local ethic committee.METHODS: This experiment was carried out in the Department of Tumor Immuonlogy, Fujian Provincial Tumor Hospital and the CaptialBio Corporation. from July 2005 to June 2006. RNA was extracted separately from CD34+ cells purified from cord blood and CD41+ cells induced from the same cord blood. The cDNA probes were synthesized by reverse transcription and purified. CD34+ cells before culturing and CD41+ cells after culturing were labeled with Cy3-dCTP and Cy5-dCTP respectively. Labeled DNA was dissolved in 30 μL hybridization fluid and hybridized at 42 ℃ over night MAIN OUTCOME MEASURES: The differential gene expression between haematopoietic stem cells and megakaryocytes involving cell signal transduction were detected by using DNA microarray analysis. According to the gene chip results,17 differentially expressed genes were selected for further analysis by RT-PCR.RESULTS: In this experiment, 3 522 differentially expressed genes were screened, including 1705 up-regulated genes and 1 817 down-regulated genes. In the 3 522 differentially expressed genes, there were 343 genes involved in cell signaling, 150 genes involved in transcription regulation, 21 genes involved in cell differentiation. The expression of the CD61 gene increased 369.83 fold, the expression of the CD41 gene increased 27.38 fold, and the expression of PF4 gene increased 24.06 folds; The expression of mitogen-activated protein kinases (MAPKs), G protein-coupled receptors (GPCRs) and members of RAS oncogene family increased mostly. The expression of the genes involved in STAT pathways, both SOCS1 and JAK2 were up-regulated, but STAT5A was down-regulated. As determined by the gene chip results, 17 differentially expressed genes were selected for further analysis by RT-PCR. GAPDH was used as the internal control, and RT-PCR results were in agreement and confirmed the finding from the gene chip expression results.CONCLUSION: Thrombopoeitin (TPO) and other hematopoietic growth factors may enhance the proliferation and differentiation of megakaryocytes derived from cord blood stem cells by GPCRs-Ras-MAPK pathway.
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Objective To analyze the characteristic of serum proteins in non-small cell lung cancer (NSCLC) patients,establish serum markers pattern for the diagnosis of NSCLC. Methods Surface enhanced laser desorption ionization time of flight mass spectormetry(SELDI-TOF-MS) technology was used to analyze serum samples. Biomarker Pattern Software (BPS) was used to detect the protein peaks. Results Sixteen significantly different protein peaks were found in serum samples in NSCLC patients and healthy controls. Eight up-regulated protein peaks and eight down-regulated protein peaks (P
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Objective To construct the tranfected cell expressing the human CXCR4 gene and to identify the effect on its immigration. Methods Total RNA was isolated from peripheral blood monouclear cell (PBMC),the full-length CXCR4 gene was amplified by RT-PCR and was inserted into plasmids PBudCE4.1 which have two promtors, after the identification by digestion and sequencing,the recombinant was transfected into K562 cell by lipofectamineTM2000. After screening culture by zeocin, stable transfected K562 cell line was established, and transcription and exression of CXCR4 were checked by flow cytometry; the chemotactic activity of K562 cell transfected and untrandfected CXCR4 was analyzed by Transell plate. Results The eukaryotic expression plasmid PBudCE4.1/ CXCR4 was constructed successfully. The stable trasfected K562/CXCR4 cell lines which highly express CXCR4 was established,the chemotactic activity of K562/CXCR4 was increased significiantly than K562. ConclusionCXCR4 transfected K562 cell line was successfully established, and it can make the basis for the further research on mechanism of extramedullary infiltration in leukemia.