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Objective:To investigate the efficacy of venetoclax-based combined regimen in treatment of adult patients with acute myeloid leukemia (AML).Methods:The data of 50 adult AML (non-acute promyelocytic leukemia) who received venetoclax-based combined regimen in the First Affiliated Hospital of Xiamen University, Dongguan People's Hospital, the First Hospital of Longyan City, Jieyang People's Hospital from December 2018 to May 2021 were retrospectively analyzed. Different doses venetoclax combined with demethylation drugs or low-dose chemotherapy regimen were used to analyze the therapeutic efficacy. The related factors influencing efficacy were analyzed by using logistic regression.Results:The composite complete remission (CR) rate of 50 AML patients was 62.0% (31/50), the overall response rate (ORR) was 76.0% (38/50); 28 patients achieved effectiveness [CR and partial remission (PR)] after the first cycle and could achieve effectiveness by 3 courses of treatment at the latest. Among 50 patients, 28 cases were newly diagnosed AML, the composite CR rate was 60.8% (17/28), ORR was 78.6% (22/28); 22 cases were recurrent and relapsed, the composite CR rate was 63.6% (14/22), ORR was 72.7% (16/22); and there was no statistically significant difference of ORR between the both groups ( χ2 = 0.23, P = 0.743). Logistic regression multivariate analysis showed age was the only independent influencing factor for the treatment effectiveness ( OR = 8.451, 95% CI 1.306-54.697, P = 0.025). The median duration time of patients receiving venetoclax treatment regimen was 4.5 months (1.1-15.0 months); 16 cases who had treatment effectiveness finally relapsed, the median time of maintaining effectiveness was 5 months (1.1-11.0 months). Additionally, the common treatment-related adverse reactions included bone marrow suppression after treatment, followed by some gastrointestinal reactions like nausea, vomiting and stomachache. In addition, no patient stopped medication for more than 1 week due to bone marrow suppression related complications. Conclusion:Venetoclax-based combined regimen shows a good short-term efficacy in treatment of AML. It is also effective and tolerable for elderly patients receiving reduced dose therapy.
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Objective:The purpose of this study was to investigate the evaluating value of modified critical care ultrasonic examination(M-CCUE) scheme for the etiological diagnosis of shock in ICU patients.Methods:The prospective study collected relevant clinical data of various shock patients admitted to the Department of Intensive Care Medicine, Henan Provincial People's Hospital from May 2020 to July 2021, including hemodynamic、blood indicators、organ/tissue perfusion and prognostic evaluation indicators.All selected patients completed the initial M-CCUE assessment within 30 minutes, were scored according to the M-CCUE score system and related data results were analyzed.Results:Ninety-three patients were included in this study,Two of them were not completed the M-CCUE assessment due to emergency treatment immediately after entering our department, and five were excluded due to inconsistent ultrasound judgments by the two physicians. In the end, a total of 86 patients were enrolled in the group. In patients applied with M-CCUE scheme,time to preliminary diagnosis and final diagnosis were (13.02±3.15)min and (67.70±20.20)min respectively, the accuracy of diagnosis was 83.7%. Among them, distributed shock accounted for 60.4%, hypovolemic shock accounted for 25.6%, cardiogenic shock and obstructive shock accounted for 3.5%, and mixed shock accounted for 7%; MCS is (13.27±4.91), M-CCUE scheme had the high sensitivity and specificity for the diagnosis of distributed shock (sensitivity 91.2%, specificity 93.9%), hypovolemic shock (sensitivity 96.0%, specificity 96.7%), cardiogenic shock (sensitivity 85.7%, specificity 98.7%) and obstructive shock (sensitivity 60.0%, specificity 100%); MCS has a good positive correlation with APACHEⅡ score ( r=0.861, P<0.001), and has no correlation with ICU cost ( r=0.012, P=0.915). There is no significant difference in MCS between the 28d death group and the recovery group ( P=0.391). Conclusions:For shock patients admitted to ICU with unknown etiology, the initial diagnosis of the cause of the M-CCUE program takes less time, has a higher correct diagnosis rate, sensitivity and specificity, and its quantitative evaluation results can predict the patient's criticality.
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Objective:To evaluate the effect of CBL combined with clinical pathway teaching in the teaching of general practitioner job-transfer training of cardiology department.Methods:From May 2018 to March 2019, a total of 63 students taking the general practitioner job-transfer training in our hospital were enrolled in this study, and randomized into control group ( n=30) and test group ( n=33). The control group used traditional teaching mode, the test group adopted CBL combined with clinical pathway teaching method. At the end of the training, the scores of theoretical and operational examination were compared between the two groups, and the satisfaction of the training was evaluated by questionnaire survey. Results:The scores of theory test and practical skills in the test group were all higher than those in the control group [(83.57±4.32) vs. (77.10±4.72), t=-5.678, P<0.001; (78.24±5.28) vs. (70.83±5.86), t=-5.279, P<0.001], and the test group was also better than the control group in the satisfaction survey of standardizing diagnosis and treatment, and improving learning interest, doctor-patient communication and physical examination skills ( P<0.05). Conclusion:In the teaching of general practitioner job-transfer training of cardiology department, CBL combined with clinical pathway teaching has shown better performance than the traditional teaching mode, which is worth promoting in general practitioner job-transfer training.
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Relapse or metastatic esophageal squamous cell carcinoma (ESCC) has poor prognosis and limited treatment options. Chemotherapy based on platinum agents combined with fluorouracil or taxanes is the standard first-line treatment for it. Molecular-targeting agents, mainly epidermal growth factor receptor inhibitors including cetuximab, panitumumab, nimotuzumab and gefitinib, have failed to improve the survival of patients with advanced ESCC. Anlotinib, one of the small molecule multi-target tyrosine kinase inhibitors, can prolong the median progression free survival in patients treated with above the second line. Compared with chemotherapy, immune checkpoint inhibitors (including nivolumab, pembrolizumab and camrelizumab) significant improve overall survival times in patients with ESCC who fail to the first line chemotherapy, and can be selected as the standard second line treatment. Immunotherapy combined with chemotherapy or anti-angiogenic therapy for first-line treatment of advanced ESCC is also being studied.
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Objective:To investigate the willingness of medical students to work in primary health care institutions.Methods:A cross-section survey was conducted to investigate the willingness and the reasons, involving 597 undergraduate medical students and 2088 junior college students.Results:The employment willingness of undergraduate medical students was relatively low (14.9%), while the employment willingness of junior college students was high (56.02%). The top three factors of low employment willingness were: less opportunities for personal development, poor working environments and welfare. Moreover, the most effective method to cultivate medical students was developing a free training project for rural-oriented medical students, and the best method to attract medical students was formulating a more beneficial comprehensive policy.Conclusion:The willingness of clinical medical students to be employed in primary health care institutions is low for the time being. It is suggested to improve their willingness by improving welfare benefits, providing personal development opportunities, and strengthening social security.
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Objective:To explore the effects of apatinib on the proliferation and apoptosis of FLT3-ITD mutant acute myeloid leukemia (AML) cells, and to explore the related mechanisms.Methods:The logarithmic growth phase FLT3-ITD mutant AML cell lines MV4-11 and MOLM-13 were treated with different concentration of apatinib for 48 hours. The cell proliferation was detected by CCK-8 method. Flow cytometry was performed to examine the effect of apatinib on apoptosis. The cell mitochondrial membrane potential changes were detected by JC-1. Then the expression changes of vascular endothelial growth factor receptor 2 (VEGFR2) pathway-related proteins were examined by Western blot.Results:Apatinib had proliferation inhibitory effects on both MV4-11 and MOLM-13 cells, and the half-maximal inhibitory concentration (IC 50) at 48 hours was (2.23±0.42) μmol/L and (4.08±2.62) μmol/L, respectively. After exposure to apatinib with increasing concentrations (10, 20, 30, and 40 μmol/L) for 48 h hours, the percentage of apoptotic cells was significantly increased in MV4-11 cells [(81.95±1.15)%, (88.80±0.23)%, (97.46±0.49)%, and (99.29±0.05)%] and MOLM13 cells [(47.30±0.87)%, (67.00±3.71)%, (82.60±2.89)%, and (98.06±5.34)%] in a dose-dependent manner, and the differences were statistically significant ( F = 6 915.0, P < 0.01; F = 5 385.0, P < 0.01). Detection of mitochondrial membrane potential by JC-1 method showed that after MV4-11 and MOLM-13 cells were treated by 10, 20, 30, and 40 μmol/L apatinib for 24 hours, the JC-1 aggregate/monomer mean fluorescence intensity (MFI) ratios were 0.45±0.06, 0.19±0.07, 0.12±0.03, 0.09±0.01, and 0.84±0.05, 0.66±0.13, 0.35±0.11, 0.27±0.02, which were different from the control group (0.67±0.15 and 0.97±0.42), and the differences were statistically significant ( F = 372.3, P < 0.05; F = 276.4, P < 0.05). Western blot was performed to detect different concentration of apatinib (2.5, 5.0 and 10.0 μmol/L) on the MV4-11 cells for 24 hours, the results showed that apatinib could down-regulate the phosphorylation of VEGFR2, Src and Stat3 in a dose-dependent manner. Conclusions:Apatinib can inhibit cell proliferation and induce apoptosis in AML with FLT3-ITD mutation. The possible mechanism is related to the down-regulation of phosphorylation of VEGFR2 and its downstream targets Src and Stat3.
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OBJECTIVE@#To evaluate the value of Sequential Organ Failure Assessment (SOFA), Simplified Acute Physiology Score Ⅱ (SAPS-Ⅱ), Oxford Acute Severity of Illness Score (OASIS) and Logistic Organ Dysfunction System (LODS) scoring systems for predicting ICU mortality in patients with sepsis.@*METHODS@#We collected the data of a total of 2470 cases of sepsis recorded in the MIMIC-III database from 2001 to 2012 and retrieved the scores of SOFA, SAPS-Ⅱ, OASIS and LODS of the patients within the first day of ICU admission. We compared with the score between the survivors and the non-survivors and analyzed the differences in the area under the ROC curve (AUC) of the 4 scoring systems. Binomial logistic regression was performed to compare the predictive value of the 4 scoring systems for ICU mortality of the patients.@*RESULTS@#In the 2470 patients with sepsis, 1966 (79.6%) survived and 504 (20.4%) died in the ICU. Compared with the survivors, the non-survivors had a significantly older mean age, higher proportion of patients receiving mechanical ventilation, and higher initial lactate level, creatinine, urea nitrogen, SOFA score, SAPS-Ⅱ score, OASIS score and LODS score ( < 0.05) but with significantly lower body weight and platelet counts ( < 0.05). The AUCs of the SOFA score, SAPS-Ⅱ score, OASIS score, and LODS score were 0.729 ( < 0.001), 0.768 ( < 0.001), 0.757 ( < 0.001), and 0.739 ( < 0.001), respectively. The AUC of SAPS-Ⅱ score was significantly higher than those of SOFA score (=3.679, < 0.001) and LODS score (=3.698, < 0.001) but was comparable with that of OASIS score (=1.102, =0.271); the AUC of OASIS score was significantly higher than that of LODS score (=2.172, =0.030) and comparable with that of SOFA score (=1.709, =0.088). For predicting ICU mortality in patients without septic shock, the AUC of SAPS-Ⅱ score was 0.769 (0.743-0.793), the highest among the 4 scoring systems; in patients with septic shock, the AUCs SAPS-Ⅱ score and OASIS score, 0.768 (0.745-0.791) and 0.762 (0.738-0.785), respectively, were significantly higher than those of the other two scoring systems. Binomial logistic regression showed the corrected SOFA, SAPS-Ⅱ, and OASIS scores, but not LODS scores, were significantly correlated with ICU mortality in patients with sepsis, and their ORs were 1.08 (95% CI: 1.03-1.14, =0.001), 1.04 (95% CI: 1.02-1.05, < 0.001), 1.04 (95% CI: 1.01-1.06, =0.001), 0.96 (95% CI: 0.89-1.04, =0.350), respectively.@*CONCLUSIONS@#The scores of SOFA, SAPS-Ⅱ, OASIS, and LODS can predict ICU mortality in patients with sepsis, but SAPS-Ⅱ and OASIS scores have better predictive value than SOFA and LODS scores.
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Humanos , Unidades de Cuidados Intensivos , Pronóstico , Curva ROC , Estudios Retrospectivos , SepsisRESUMEN
Follicular lymphoma (FL) is the most common indolent B-cell non-Hodgkin lymphoma. The overall survival of FL is near 15 years. However, the survival would be significantly shortened in refractory, early-relapsed or transformed setting. The 60th American Society of Hematology (ASH) Annual Meeting reported several latest and optimal approaches to relapsed/refractory FL, with a focus on immune-based therapies and target agents for FL. This paper reviews and makes comments about these clinical trials.
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Objective@#To explore the clinical characteristics and prognosis of pulmonary tuberculosis in children with human immunodeficiency virus (HIV)/ acquired immunedeficiency syndrome (AIDS).@*Methods@#A retrospective analysis was made on the clinical data of 23 children with HIV/AIDS and tuberculosis who were cultured positive for Mycobacterium tuberculosis, including general data, laboratory examinations, imaging data and disease outcomes.@*Results@#The percentage of CD4+ T lymphocytes<50/mm3 was 43.48% (10≤23) in 23 children. The proportion of appetite loss, fever, cough and fatigue was 86.95%, 82.61%, 82.61% and 78.26% respectively. Atypical symptoms such as rash, joint muscle stiffness and vomiting could be seen. The proportion of multi-site and patchy shadow on chest radiography was 47.83% and 43.48% respectively. There were 1 case of oral mucosal leukoplakia, 1 case of herpes zoster and 1 case of Pneumocystis carinii pneumonia. Nineteen children were followed up regularly after they were discharged from hospital. In 2 cases the treatments were ineffective or the diseases worsened, and two cases died.@*Conclusions@#The clinical manifestations of children with HIV/AIDS complicated with tuberculosis were lack of specificity. The general manifestations and extrapulmonary manifestations were serious. Chest imaging manifestations are mostly multi-site and patchy shadows. Early diagnosis and treatment of HIV/AIDS in children are very important.
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Objective Doppler ultrasonography was used to screen the incidence of central venous catheter (CVC) thrombosis in severe patients to observe the incidences of catheter-related thrombosis (CRT) at subclavian (SC) and internal jugular (IJ) venous insertion sites, and to analyze the factors affecting the thrombosis. Methods One hundred and twenty three adult patients with IJ or SC CVC admitted to the Department of Intensive Care Unit (ICU) of Zhongnan Hospital of Wuhan University from May to December 2015 were enrolled to be the research objects, they were divided into an IJCVC group (35 cases) and a SCCVC group (88 cases) according to different catheterization sites; they were divided into an operation group (85 cases) and a non-operation group (38 cases) according to whether operation was performed or not; and they were also divided into an anticoagulation group (25 cases) and a non-anticoagulation group (98 cases) according to whether anticoagulation therapy was used or not. Doppler ultrasonography was performed every day to observe the incidences of CRT during ICU stay. Results One hundred and twenty-three patients were included in this study. CRT was detected in 11 (8.9%) patients, with an incidence of 22.1 per 1 000 catheter-days. All the 11 cases with CRT were presented within 3 days after the insertion, with 9 cases (81.8%) on the first day and 2 cases (18.2%) on the third day. The incidence of CRT in SCCVC group was significantly lower than that in IJCVC group [5.7% (5/88) vs. 17.1% (6/35), P < 0.05], with the rates of 12.6 and 59.4 per 1 000 catheter-days, respectively. There were no statistical significant differences in the incidences of CRT between operation group and non-operation group [11.8% (10/85) vs. 2.6% (1/38)], and between anticoagulation group and non-anticoagulation group [8.0% (1/25) vs. 9.2% (2/98), both P > 0.05]. Conclusions The incidence of CRT at IJCVC site is estimated to be 3-times higher than that at SCCVC site, anticoagulants or surgical operation may have impacts on the incidence of CRT, although there were no statistically significant differences. The CRT usually occurs within 3 days after the catheter insertion. Frequent bedside ultrasonography in the first 3 days after catheterization can confirm the diagnosis and guide clinical treatment.
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Objective To investigate the effects of gemcitabine and ABT-199 on proliferation inhibition and apoptosis induction of Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL) cell line SUP-B15, and to explore its synergistic mechanism. Methods SUP-B15 cells in logarithmic growth phase were treated with gemcitabine (0.025 and 0.050 μmol/L), ABT-199 (0, 0.5, 1.0, 2.0, 4.0, 8.0 μmol/L) or two drugs for 24 h. Cell proliferation was detected by CCK-8 method, apoptosis was detected by flow cytometry (FCM), mitochondrial membrane potential was detected by JC-1 method, and expression of mitochondrial apoptosis pathway-related protein was analyzed by Western blot. Results The 50 ％ inhibitory concentration (IC50) of SBT-B15 cells treated with ABT-199 for 24 h was (4.13±0.89) μmol/L. However, gemcitabine (0.025, 0.050 μmol/L) significantly enhanced the inhibitory effect of ABT-199 on proliferation of SUP-B15 cells, the IC50 values were (2.23 ±0.73) and (1.15 ±0.45) μmol/L, respectively. The results of FCM assay showed that compared with the monotherapy group [(7.33±1.54)％], 0.025 umol/L gemcitabine combined with ABT-199 (1.0 and 2.0 μmol/L) acted on SUP-B15 cells for 24 h, the proportions of apoptotic cells were (32.42±1.45) ％and (44.33±1.86) ％, the difference was statistically significant (F=70.78, P<0.001);compared with the monotherapy group [(9.60 ±2.76) ％], 0.05 μmol/L gemcitabine combined with ABT-199 (1.0 and 2.0 μmol/L) acted on SUP-B15 cells for 24 h, the proportion of apoptotic cells increased to (47.63 ± 3.81) ％ and (58.73 ±4.33) ％, respectively, and the difference was statistically significant (F= 79.21, P<0.001). The JC-1 experiment showed that treated with ABT-199 and gemcitabine for 12 h, the percentage of depolarizing cell was significantly higher than that in single agent group, and the difference was statistical significant (P<0.001). Western blot showed that the anti-apoptotic proteins bcl-2, bcl-xL and Mcl-1 decreased after treated by gemcitabine combined with ABT-199 for 12 h. Conclusion Gemcitabine could enhance the proliferation inhibition and induce apoptosis of Ph+ALL cells by ABT-199, and its mechanism may be related to down-regulation of anti-apoptosis-related proteins.
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BACKGROUND: Actinic keratosis (AK) was an intraepidermal tumor which caused by ultraviolet irradiation-induced skin damage. OBJECTIVE: The aim was to screen biomarkers for development of skin disease by comparing the gene expression profiles between cutaneous squamous cell carcinoma (CSCC) and AK. METHODS: GSE45216 with 30 cutaneous squamous cell carcinoma patients and 10 actinic keratosis patients were downloaded and significance analysis of microarrays was processed to screen differently expressed genes (DEGs). Fisher's exact test was processed for DEGs enrichment. Pathway relationship network systematically reflected the signal conduction and synergism between enriched pathways based on Kyoto Encyclopedia of Genes and Genomes database. Gene co-expression network was constructed according to gene expression data. Quantitative real-time-PCR was used to verify screened biomarkers. RESULTS: Total 410 DEGs were screened and enriched into various functions, such as signal transduction and negative regulation of apoptotic process. They also participated into cytokine-cytokine receptor interaction and focal adhesion. The pathway relationship network was constructed with 27 nodes. Hub nodes with higher degree of this network were mitogen-activated protein kinase signaling pathway and apoptosis. The gene co-expression network was constructed with 39 nodes. Thereinto, hub node was ELOVL fatty acid elongase. The expression levels of ELOVL4 and HPGD were significantly higher in CSCC samples than that in AK samples, while the expression levels of INHBA and LAMC2 in CSCC samples were significantly lower than that in AK samples. CONCLUSION: These screened genes, including ELOVL4, HPGD, INHBA and LAMC2, played important roles in transformation from AK to CSCC.
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Humanos , Actinas , Apoptosis , Biomarcadores , Carcinoma de Células Escamosas , Diagnóstico , Células Epiteliales , Adhesiones Focales , Expresión Génica , Genoma , Queratosis Actínica , Tamizaje Masivo , Proteínas Quinasas , Transducción de Señal , Enfermedades de la Piel , Piel , TranscriptomaRESUMEN
Objective To evaluate effects of targeted silencing of growth arrest and DNA damage inducible gene 45α (Gadd45α) by small interference RNA (siRNA) on the invasion and migration of a cutaneous squamous cell carcinoma cell line A431.Methods Real-time fluorescence-based quantitative PCR and Western blot analysis were performed to detect the mRNA and protein expression of A431 and Colon16 cells respectively,and then A431 cells with highly expressed Gadd45α served as a research object.Cultured A431 cells were divided into 3 groups:experimental group transfected with Gadd45α-siRNA-1,negative control group transfected with negative control siRNA,and blank control group receiving no treatment.After the RNA interference,the mRNA and protein expression of Gadd45α in the above 3 groups were measured by real-time fluorescence-based quantitative PCR and Western blot analysis,respectively,and the effect of the RNA interference on the invasion and migration abilities of A431 cells was evaluated by Transwell and wound scratch assays.Results Gadd45α mRNA and protein were highly expressed in the A431 cells.After the RNA interference,the experimental group showed markedly lower mRNA and protein expressions of Gadd45 in the A431 cells (0.286 ± 0.013,0.33 ± 0.007,respectively) compared with the negative control group (1.028 ± 0.183,0.87 ± 0.002,respectively)and blank control group (1.001 ± 0.057,0.86 ± 0.004,respectively),and there were significant differences in the mRNA and protein expressions of Gadd45 among the 3 groups (F =5 893.857,2 763.000,both P ＜ 0.001).The number of A431 cells crossing the polycarbonate membrane was higher in the experimental group (66.33 ± 3.79) than in the negative control group (26.00 ± 4.36) and the blank control group (28.33 ± 4.16),and there was a significant difference among the 3 groups (F =20.084,P =0.002).Moreover,the wound scratch assay showed that the number of migrating A431 cells per high-power field was significantly higher in the experimental group than in the negative control group and the blank control group (315.33 ± 6.66,154.67 ± 2.08,130.67 ± 3.51 respectively;F =1 676.255,P ＜ 0.001).Conclusion Gadd45α is highly expressed in the cutaneous squamous cell carcinoma cell line A431,and targeted silencing of Gadd45α gene can enhance the in vitro invasion and migration abilities of A431 cells.
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Objective To evaluate the effect of electric stimulation of vagus nerves on the expression of aquaporin-4 (AQP-4) in brain tissues of rats with endotoxemia.Methods Forty-eight adult male Sprague-Dawley rats,aged 2 months,weighing 200-250 g,were divided into 4 groups (n=12 each) using a random number table:sham operation group (S group),endotoxemia group (E group),vagus nerve transection group (VNT group) and vagus nerve transection plus vagus nerve stimulation group (VNT+VNS group).The model of endoxemia was established by injection of lipopolysaccharide 10 mg/kg via the femoral vein of anesthetized rats.Left cervical vagotomy was performed at 30 min before injection of lipopolysaccharide in VNT and VNT+VNS groups.In VNT+VNS group,electric stimulation of the distal end of the left vagus nerve was performed immediately after the end of surgery.Stimulation parameters were as follows:current intensity 0.5 mA,pulse width 0.5 ms,frequency 20 Hz,once every 5 min,30 s per time,lasting for 1 h.Blood samples were collected from the abdominal aorta at 6 h after establishment of the model,and then the rats were sacrificed and brains were removed.The level of IL-1β in plasma and brain tissues and content of AQP-4 in brain tissues were measured by enzyme-linked immunosorbent assay.The Evans blue (EB) content in brain tissues and brain water content were determined.Results Compared with S group,the levels of IL-1β in plasma were significantly increased,and the contents of IL-1β,AQP-4 and EB in brain tissues and brain water content were increased in E,VNT and VNT+VNS groups (P＜0.01).Compared with E group,the levels of IL-1β in plasma were significantly decreased,and the contents of IL-1β,AQP-4 and EB in brain tissues and brain water content were decreased in VNT+VNS group (P＜0.01),and no significant change was found in the indexes mentioned above in VNT group (P＞ 0.05).Conclusion The mechanism by which electric stimulation of vagus nerves reduces brain injury may be related to decreased content of AQP-4 in brain tissues of rats with endotoxemia.
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Objective To investigate in vitro effects of tanshinoneⅡA on the autophagy of A375 melanoma cells and related signaling pathway. Methods Some cultured A375 cells were divided into 5 groups to be treated with tanshinoneⅡA at concentrations of 0.5, 1, 2 and 4 mg/L, and DMEM containing 0.1% dimethyl sulfoxide (DMSO), respectively, for 24, 48, 72 hours. Methyl thiazol tetrazolium (MTT) assay was performed to estimate the proliferative activity of A375 cells. Some cultured A375 cells were divided into 4 groups to be treated with 1, 2 and 4 mg/L tanshinone ⅡA(1?, 2?and 4?mg/L tanshinone group), and DMEM containing 0.1% DMSO (control group), respectively, for 48 hours. Then, flow cytometry was conducted to count autophagosome?positive cells, and Western blot analysis to determine protein expression of autophagy?associated proteins Beclin?1, microtubule?associated protein 1 light chain 3 (LC3)?Ⅱ, phosphatidylinositol 3?kinase(PI3K), protein kinase B(Akt), mammalian target of rapamycin (mTOR)and p70 ribosomal protein S6 kinase 1(p70S6K1). Results MTT assay showed that 24?, 48?, 72?hour treatments with tanshinone ⅡA at concentrations of 0.5, 1, 2 and 4 mg/L all could inhibit the proliferative activity of A375 cells, and the inhibitory effects increased in a dose? and time?dependent manner(F = 2 564.12, 1 235.25, both P < 0.05). The percentage of autophagosome?positive cells and protein expression of Beclin?1 and LC3?Ⅱincreased gradually and significantly in the 1?, 2?and 4?mg/L tanshinone groups(autophagosome?positive cells: 6.91% ± 0.35%, 13.11% ± 0.73%, 25.51% ± 0.83%, respectively; Beclin?1: 0.33 ± 0.01, 0.53 ± 0.04, 0.63 ± 0.02, respectively; LC3?Ⅱ: 0.41 ± 0.01, 0.52 ± 0.02, 0.64 ± 0.02, respectively), after 48?hour treatment, which were significantly different between the tanshinone groups(all P<0.05), and higher in the tanshinone groups than in the control group(0.41%±0.02%;0.09 ± 0.02;0.21 ± 0.01, all P<0.05). However, the protein expression of PI3K, phosphorylated Akt(p?Akt), p?mTOR and p?p70S6K1 in the PI3K?Akt?mTOR?p70S6K1 signaling pathway decreased gradually and significantly with the increase in tanshinone concentrations after 48?hour treatment, and were significantly lower in all the tanshinone groups than in the control group (all P < 0.05). Conclusion Tanshinone ⅡA can promote the auophagy of A375 cells, likely by blocking the PI3K?Akt?mtTOR?p70S6K1 signaling pathway.
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Objective To evaluate effects of tanshinone ⅡAon the invasion and migration of melanoma A375 cells,as well as on the mRNA and protein expression of CXC chemokine receptor type 7 (CXCR7).Methods In vitro cultured A375 cells were divided into 4 groups to be treated with tanshinone ⅡA at different concentrations of 1,2 and 4 mg/L,and 0.1％ dimethyl sulfoxide (DMSO) (control group) for 48 hours,respectively.Wound scratch assay and Transwell invasion assay were conducted to estimate the migratory and invasive abilities of A375 cells,respectively,and real-time fluorescence-based quantitative PCR (qRT-PCR) and Western blot analysis to determine the mRNA and protein expression of CXCR7 in A375 cells,respectively.Results After 48-hour treatment,the 1-,2-and 4-mg/L tanshinone ⅡA groups showed significantly decreased number of A375 cells crossing the polycarbonate membrane per high-power field (× 200) (71.00 ± 4.00,51.00-± 2.00 and 37.00 ± 3.61,respectively) in Transwell invasion assay,as well as decreased number of A375 cells migrating to the scratch zone (301 ± 3.00,253.00 ± 3.61 and 126.00 ± 7.00,respectively) in wound scratch assay,compared with the control group (105.33 ± 6.51,332.00 ± 6.24,respectively,all P ＜ 0.05).Additionally,qRT-PCR and Western blot analysis revealed that the mRNA and protein expression of CXCR7 was significantly lower in the 1-,2-and 4-mg/L tanshinone ⅡA groups than in the control groups (CXCR7 mRNA:0.63-± 0.04,0.44 ± 0.02 and 0.31 ± 0.01 vs.1.00 ± 0.02;CXCR7 protein:0.573 ± 0.015,0.416 ± 0.011 and 0.260-± 0.055 vs.0.9000 ± 0.010;all P ＜ 0.05).Moreover,inhibitory effects of tanshinone ⅡA on the migration and invasion of A375 cells,as well as on the mRNA and protein expression of CXCR7,were significantly enhanced with the increase of tanshinone ⅡA concentrations (all P ＜ 0.05).Conclusion Tanshinone ⅡA can inhibit the migratory and invasive abilities of melanoma A375 cells by down-regulating CXCR7 expression.
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Objective To explore the association between toll-like receptor 7 (TLR7) single nucleotide polymorphisms (SNP) and susceptibility of hand, foot and mouth disease caused by enterovirus (EV)71 infection.Methods The genotype of SNP (rs179019 and rs3853839) was determined in 775 EV7l-infected cases (including 439 mild cases and 336 severe cases) and 748 healthy control cases with TaqMan assay.The difference of allele frequencies was compared.The difference of TLR7 mRNA expression in peripheral blood mononuclear cells (PBMCs) derived from different SNP genotype carriers was detected.PBMCs derived from different SNP genotype carriers were stimulated by imiquimod and the TLR7-specific interferon-α(IFN-α) and interleukin-6 (IL-6) secretions were detected.Logistic regression was used to analyze for genotype frequency.Results The frequencies of rs3853839 genotype CC and CG in female patients of severe group were significantly higher than mild group (rs3853839 GC: OR=0.36,95%CI:0.14-0.82, P=0.01;rs3853839 CC: OR=0.19,95%CI:0.11-0.69,P=0.01).In addition, the frequency of rs3853839 genotype C in severe male group was significantly higher compared with that in mild group (OR=0.35,95%CI:0.19-0.63, P=0.01).Female carriers with rs3853839 genotype CC had significantly lower TLR7 mRNA expression than genotype GC and GG (CC vs GG: P=0.005;CC vs GC: P=0.016).Male carriers with rs3853839 genotype C also had significantly lower TLR7 mRNA expression than genotype G (C vs G: P=0.004).After stimulation of imiquimod, the expression of IFN-α (CC vs GG, P=0.001;CC vs GC: P=0.026) and IL-6 productions (CC vs GG: P=0.001;CC vs GC: P=0.011) were significantly lower in female carriers with rs3853839 genotype CC.The same patterns were observed in male carriers with rs3853839 genotype CC (IFN-α: P=0.003;IL-6: P=0.018).Conclusions The rs3853839C allele is the risk factor of severe infection of EV71, which may be due to specific cytokine profiles in rs3853839C allele carriers in children.
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Objective To explore the expression and significance of COX-2 ,MMP-9 and PTEN in colonic adenocarcinoma tissues .Methods Seventy-two cases of pathologically archived paraffin specimens after colonic adenocarcinoma radical operation in the hospital from March 2014 to May 2016 were collected ,30 cases of colonic adenoma tissues and 30 cases of normal mucosal mem-brane tissues served as the controls .The expressions of COX-2 ,MMP-9 and PTEN were detected by adopting the immunohisto-chemical SP method .Then the correlation between COX-2 ,MMP-9 and PTEN with clinicopathological features of colonic adenocar-cinoma was analyzed .Results The positive expression rate of COX-2 and MMP-9 in colonic adenocarcinoma tissues was significant-ly higher than that in colonic adenoma tissues and normal colon mucosal membrane tissues (P<0 .05);the positive expression rate of PTEN was significantly lower than that in colonic adenoma tissues and normal colon mucosal membrane tissues (P<0 .05) .The expression of COX-2 ,MMP-9 and PTEN in colonic adenocarcinoma was correlated with the tumor invasive depth ,lymph node me-tastasis and TNM staging(P<0 .05) ,while had no correlation with sex ,age ,tumor morphology ,tumor size and differentiation de-gree(P>0 .05) .COX-2 ,MMP-9 and PTEN expressions showed negative correlation (r= -0 .260 ,-0 .282 ,P<0 .05) ,COX-2 and MMP-9 expression showed a positive correlation (r=0 .335 ,P=0 .004) .Conclusion The abnormal expression and interaction of COX-2 ,MMP-9 and PTEN are closely correlated with the occurrence ,invasion and metastasis of colonic adenocarcinoma .Their combined detection has an important significance for early diagnosis and prognosis assessment of colonic adenocarcinoma .
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Aimed at the current plight of medical students' professionalism education,such as ignoring the top -level design and the overall plan but emphasizing practice,ignoring the permeability of professional spirit but emphasizing the impartation of professional knowledge,ignoring humanities but emphasizing professional issues in curriculum setting,Capital Medical University advocated the all-dimensional education philosophy implenented by all staff through the whole process,made top-level design scientifically for medical students' professionalism education.The university strengthened professionalism through teaching,permeated professionalism through a series of educational activities,consolidated professionalism through clinical practice,and thus to strengthen the cultivation of medical students' professionalism and realize scientific education by all staff and throughout the whole process.
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Human trials are necessary to medical development,but the experiments need to be reviewed under the condition of informed consent.The current ethical review of informed consent in China exist some limits.For example,the corresponding normative legal status is low,the tracing review of informed consent becomes a mere formality,and the ethical review mechanism is not perfect,and so on.We should strengthen the examination of the ethical examination of human trials,increase the tracking and examination of informed consent of human trials,and improve the supporting mechanism of ethical review,and thus to safeguard the life and health rights and interests and personality dignity.