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1.
Zhongguo fei'ai zazhi (Online) ; Zhongguo fei'ai zazhi (Online);(12): 881-888, 2024.
Article in Chinese | WPRIM | ID: wpr-1010097

ABSTRACT

BACKGROUND@#Drug resistance is the main cause of high mortality of lung cancer. This study was conducted to investigate the effect of folic acid (FA) on the resistance of non-small cell lung cancer (NSCLC) cells to Osimertinib (OSM) by regulating the methylation of dual specificity phosphatase 1 (DUSP1).@*METHODS@#The OSM resistant NSCLC cell line PC9R was establishd by gradually escalation of OSM concentration in PC9 cells. PC9R cells were randomly grouped into Control group, OSM group (5 μmol/L OSM), FA group (600 nmol/L FA), methylation inhibitor decitabine (DAC) group (10 μmol/L DAC), FA+OSM group (600 nmol/L FA+5 μmol/L OSM), and FA+OSM+DAC group (600 nmol/L FA+5 μmol/L OSM+10 μmol/L DAC). CCK-8 method was applied to detect cell proliferation ability. Scratch test was applied to test the ability of cell migration. Transwell assay was applied to detect cell invasion ability. Flow cytometry was applied to measure and analyze the apoptosis rate of cells in each group. Real-time fluorescence quantitative polymerase chain reaction (RT-qPCR) method was applied to detect the expression level of DUSP1 mRNA in cells. Methylation specific PCR (MSP) was applied to detect the methylation status of the DUSP1 promoter region in each group. Western blot was applied to analyze the expression levels of DUSP1 protein and key proteins in the DUSP1 downstream mitogen-activated protein kinase (MAPK) signaling pathway in each group.@*RESULTS@#Compared with the Control group, the cell OD450 values (48 h, 72 h), scratch healing rate, number of cell invasions, and expression of DUSP1 in the OSM group were obviously decreased (P<0.05); the apoptosis rate, the methylation level of DUSP1, the expression of p38 MAPK protein, and the phosphorylation level of extracellular regulated protein kinases (ERK) were obviously increased (P<0.05); the cell OD450 values (48, 72 h), scratch healing rate, number of cell invasions, and expression of DUSP1 in the DAC group were obviously increased (P<0.05); the apoptosis rate, the expression of p38 MAPK protein, the phosphorylation level of ERK, and the methylation level of DUSP1 were obviously reduced (P<0.05). Compared with the OSM group, the cell OD450 values (48, 72 h), scratch healing rate, number of cell invasions, and expression of DUSP1 in the FA+OSM group were obviously decreased (P<0.05); the apoptosis rate, the methylation level of DUSP1, the expression of p38 MAPK protein, and the phosphorylation level of ERK were obviously increased (P<0.05). Compared with the FA+OSM group, the cell OD450 values (48, 72 h), scratch healing rate, number of cell invasions, and expression of DUSP1 in the FA+OSM+DAC group were obviously increased; the apoptosis rate, the methylation level of DUSP1, the expression of p38 MAPK protein, and the phosphorylation level of ERK were obviously reduced (P<0.05).@*CONCLUSIONS@#FA may inhibit DUSP1 expression by enhancing DUSP1 methylation, regulate downstream MAPK signal pathway, then promote apoptosis, inhibit cell invasion and metastasis, and ultimately reduce OSM resistance in NSCLC cells.


Subject(s)
Humans , Carcinoma, Non-Small-Cell Lung/genetics , Lung Neoplasms/genetics , Dual Specificity Phosphatase 1/pharmacology , Cell Proliferation , p38 Mitogen-Activated Protein Kinases/pharmacology , Methylation , Apoptosis , Cell Line, Tumor
2.
Article in Chinese | WPRIM | ID: wpr-992157

ABSTRACT

Objective:To investigate the regulatory role of defferentially expressed LOC107987438 in the pathogenesis of depressive disorder and provide a theoretical basis for its clinical application in depressive disorder.Methods:Differential expression of LOC107987438 was verified by quantitative real-time polymerase chain reaction(qRT-PCR)in peripheral blood monocular cells(PBMCs)of 60 patients with depressive disorder and 60 health controls. In addition, its diagnostic value was assessed by receiver operating characteristic(ROC)curves. Based on the ceRNA mechanism of lncRNA, the miRDB database was applied to predict the target miRNAs of LOC107987438, and the miRNAs with target score ≥ 80 among them were screened out.The screened miRNAs were then used to predict their potential target mRNAs through four databases which were TargetScan 8.0, miRTarBase, mirDIP and miRPathDB. Moreover, the predicted target mRNAs were annotated for gene ontology(GO)function annotation and tokoyo encyclopedia of genes and genomes(KEGG) pathway enrichment analysis via ClusterProfiler 4.0.5 package of R 4.1.1. Finally, a protein-protein interaction network was constructed using the STRING 11.5 platform to retrieve the interacting genes.Results:The qRT-PCR results showed that normalized expression of LOC107987438 in PBMCs of patients with depressive disorder was higher than that in health controls(depressive disorder: 2.084±1.357, health controls: 1.000±0.660, P<0.001). The ROC curve results showed that the area under curves(AUC)of LOC107987438 was 0.759(95% CI: 0.675-0.842, P<0.05), indicating its high potential diagnostic value. Bioinformatics analysis showed that hsa-miR-4670-3p, hsa-miR-619-3p, hsa-miR-6721-5p and hsa-miR-297 were the miRNAs with high bindings to LOC107987438. The results of KEGG signaling pathway enrichment revealed that hypoxia-inducible factor 1(HIF-1)signaling pathway, phosphatidylinositol 3-kinase-AKT(PI3K-Akt) signaling pathway and erythroblastic oncogene B(ErbB) signaling pathway were closely associated with depressive disorder. Among the top ten key genes screened by the protein-protein interaction network, kirsten rats arcomaviral oncogene homolog(KRAS), androgen receptor(AR), cyclic-AMP response binding protein1(CREB1), insulin-like growth factor 1(IGF1), cyclin-dependent kinase inhibitor 1B(CDKN1B) and calcium/calmodulin-dependent protein kinase type Ⅱ alpha(CAMK2A)were strongly associated with depressive disorder. Conclusion:The establishment of ceRNA regulatory network of LOC107987438 provides a theoretical basis for exploring the pathophysiology of depressive disorders.

3.
Chinese Journal of School Health ; (12): 185-189, 2021.
Article in Chinese | WPRIM | ID: wpr-873634

ABSTRACT

Objective@#To analyze myopia related factors among students in Shanghai, to explore associated risky behaviors associated with mild, moderate, high myopia,so as to provide the evidence for the implementation of home and school combination intervention measures.@*Methods@#Six primary and secondary schools (2 primary schools, 2 middle schools and 2 high schools) were selected from each district of Shanghai. The primary schools began to investigate from the fourth grade. All the students in the selected classes participated in the vision test and questionnaire survey. Chi square test was used for categorical data analysis. The relationship between myopia and related behaviors was analyzed by multivariate Logistic analysis.@*Results@#The prevalence of visual-related risky behaviors such as short outdoor time during the day, lack of sleep, long after-school reading and writing time, poor reading and writing posture, and longtime-using mobile electronic screen was higher in girls than in boys (P<0.05), boys were more likely than girls to use computer for long time and read books/electronic screen in sunlight (P<0.05). The group with 3 hours or more than of reading and writing compared with the less than 2 hours, the OR value of mild myopia model was 1.31(1.20-1.44), moderate myopia model was 1.78(1.62-1.96), severe myopia model was 2.37(2.07-2.71). In the model of moderate and high myopia, reading and writing posture, frequency of eye relax, outdoor activity time and watching TV time were also included.@*Conclusion@#The prevalence of myopia related behaviors among primary and secondary school students is high, and there are significant gender differences among different behaviors. Students reading and writing time should be strictly controlled after school. Intervention strategies and measures should be carried out according to the characteristics of different ages and genders.

4.
Article in Chinese | WPRIM | ID: wpr-753399

ABSTRACT

The theories of pathophysiology come from experimental research,and experimental teaching is an important part of pathophysiology course.Experimental teaching can cultivate the abilities of independent thinking and comprehensive analysis in students,improve their practical skills,and enhance their understanding and application of theoretical knowledge.However,teaching reform should be carried out due to the drawbacks of current pathophysiological experimental teaching.With the teaching idea centered on learning,the quality of pathophysiological experimental teaching can be enhanced by rational arrangement of experimental courses,optimization of teaching contents,and comprehensive application of various teaching models,so as to effectively improve the level of theoretical knowledge and comprehensive practical ability among students.

5.
Article in Chinese | WPRIM | ID: wpr-744144

ABSTRACT

Pathophysiology is a subject that studies the occurrence,development and mechanism of diseases.It plays important roles in medical education and is an important and difficult point in medical education.Based on our teaching experience and the characteristics of pathophysiology,this paper puts forward the idea of “Focus on learning”,aiming to resolve the problems of insufficient communication,unsound teaching design and single teaching method,etc.existed in teaching process.The active communication with students,a good job of teaching design and the reasonable application of various teaching methods and techniques should be carried out to improve the teaching effect of pathophysiology.

6.
Zhongguo zhenjiu ; (12): 25-30, 2017.
Article in Chinese | WPRIM | ID: wpr-323717

ABSTRACT

<p><b>OBJECTIVE</b>To observe the improvement of acupuncture and moxibustion on symptoms of-deficiency syndrome as well as their differences on the parameters of heart rate variability (HRV).</p><p><b>METHODS</b>Thirty patients with-deficiency syndrome and 15 healthy volunteers were recruited. Thirty patients with-deficiency syndrome were randomly assigned into an acupuncture group and a moxibustion group, 15 cases in each one. Fifteen healthy volunteers were allocated as a healthy control group. Patients in the acupuncture group and healthy control group were treated with acupuncture while patients in the moxibustion group were treated with moxibustion. Guanyuan (CV 4) and Zusanli (ST 36) were chosen for treatment, once every other day, for totally 10 times. All the patients were evaluated with-deficiency assessment scale (QDAS) and HRV parameters before treatment, after 4th treatment and after all treatment. The correlation was analyzed between QDAS and HRV parameters, and HRV parameters were compared among the three groups before treatment, after 4th treatment and after all treatment.</p><p><b>RESULTS</b>Compared before treatment, the scores of QDAS were decreased in the acupuncture group and the moxibustion group after 4th treatment and after all treatment (all<0.05); after all treatment the score of QDAS in the moxibustion group was lower than that in the acupuncture group (<0.05). The HRV parameters of-deficiency syndrome were significantly lower than those of healthy volunteers with higher correlation with QDAS. Compared before treatment, the mean heart rate was decreased after treatment (<0.05), while total HRV and low frequency were increased in the moxibustion group (both<0.05). The mean heart rate in the healthy control group was increased after treatment (<0.05). The differences of HRV parameters before and after treatment were not significant in the acupuncture group (all>0.05).</p><p><b>CONCLUSIONS</b>Total HRV can reflect the severity of-deficiency syndrome. Both acupuncture and moxibustion can improve symptoms of-deficiency patients, which is superior in moxibustion. The possible mechanism is likely to be related with improved sustainable activation of autonomic nervous system.</p>

7.
Chinese Journal of Hematology ; (12): 379-383, 2017.
Article in Chinese | WPRIM | ID: wpr-808743

ABSTRACT

Objective@#To evaluate the efficacy and safety of maintenance therapy with reduced dose of rhTPO in the patients with primary immune thrombocytopenia (ITP) who attained stable platelet (PLT) counts after daily administration of rhTPO.@*Methods@#Treatment was started with a daily administration of rhTPO (300 U/kg) for 2 consecutive weeks. Patients who attained stable PLT≥50×109/L were enrolled to maintenance therapy starting with every other day administration of rhTPO, then adjusted dose interval to maintain platelet count (30-100) ×109/L.@*Results@#A total of 91 eligible patients were enrolled. Fourteen patients discontinued the study due to noncompliance (12/14) and investigator decision (2/14) . Among 77 patients who completed the study, 38 patients with the administration of rhTPO at every other day or less could maintain PLT≥30×109/L for 12 weeks. The percentage of patients with a platelet response (PLT≥30×109/L) at 4th week, 8th week and 12th week of maintain therapy was 92.6% (63/68) , 82.7% (43/52) and 85.0% (34/40) , respectively. Median platelet counts remained in the range of (70-124) ×109/L. The overall incidence of rhTPO-related adverse events was 7.7%. All the adverse events were generally mild.@*Conclusion@#Extending the dose interval of rhTPO is feasible to maintain stable platelet count in the patients with ITP, but the optimal dose interval is uncertain and might vary with individuals.

8.
China Pharmacy ; (12): 4268-4271, 2017.
Article in Chinese | WPRIM | ID: wpr-704424

ABSTRACT

OBJECTIVE:To establish a method for simultaneous determination of eugenol and thymol in mummification pastes.METHODS:HPLC method was adopted.The determination was performed on Wonda Cract C18 column with mobile phase consisted of methanol-0.2% phosphoric acid (gradient elution) at the flow rate of 1.0 mL/min.The detection wavelength was 274 nm,and column temperature was set at 25 ℃.The sample size was 10 μL.RESULTS:The linear ranges of eugenol and thymol were 0.02-0.19 mg/mL (r=0.999 7) and 0.03-0.30 mg/mL (r=0.999 6).RSDs of precision,stability and reproducibility tests were all lower than 2.0%.The recoveries were 95.85%-99.84%(RSD=1.11%,n=9) and 95.81%-100.91%(RSD=1.59%,n=9).CONCLUSIONS:The method is simple and accurate,and can be applied to simultaneous determination of eugenol and thymol in mummification pastes.

9.
Article in Chinese | WPRIM | ID: wpr-668131

ABSTRACT

Objective:To investigate the efficacy and safety of SIMI mouthguard paint(test group) in the treatment of enamel demineralization during orthodontic therapy with fixed applince.Methods:152 cases underwent orthodontic therapy with fixed applince were included in a randomized,open,positive control trial,and were treated by SIMI and Duraphant fluoride toothpast (control group) respectively(n =76).The enamel opaque spot was observed before and 3 months after using the products.The oral mucosa reactions,asthma attacks or stomach nausea and other adverse events were recorded.Results:150 cases (n =75) completed the trial.The results showed that the test group was non-inferior compared with the control group.No adverse event was found in both groups.Conclusion:SIMI mouthguard paint is effective in control of enamel demineralization during orthodontic therapy with fixed applince.

10.
Article in Chinese | WPRIM | ID: wpr-478801

ABSTRACT

ObjectiveTo compare the therapeutic efficacy between warm needling and Western medication in treating chronic atrophic gastritis.MethodSixty patients were randomized into an observation group and a control group, 30 cases in each group. The observation group was intervened by warm needling, selecting Guanyuan (CV4), Qihai (CV6), Zusanli (ST36), Xuehai (SP10), and Geshu (BL17); The control group was by Western medication, including Omeprazole, Amoxillin, Metronidazole, etc. The clinical efficacies were compared after 8-week treatment. Besides, gastroscopewas ordered at outset and after 8-week treatment to compare the therapeutic efficacies.ResultIn comparing the clinical symptoms, the total effective rate was 93.3% in the observation group versus 70.0% in the control group (P<0.05); the gastroscope scores dropped significantly in both groups after 8-week treatment (P<0.05), and the score of the observation group was significantly lower than that of the control group (P<0.05). ConclusionAcupuncture-moxibustion can significantly improve the clinical symptoms and gastroscopic results in patients with chronic gastritis, and its therapeutic efficacy is superior to that of Western medication.

11.
Article in Chinese | WPRIM | ID: wpr-597520

ABSTRACT

Purpose To observe the effect of Rongban Tongmai Granules on thrombosis and blood viscosity of in vitro rat model of blood stasis, and to study the activating blood circulation effect of the drug.Methods To observe the effect of the Rongban Tongmai Granules on thrombosis and blood viscosity of in vitro rat model of stasis, subcutaneous inject rat with epinephrine hydrochloride, and then copy "blood stasis" model by ice water stimulation in rats.Results According to a continuous 7 days′intragastric administration of Rongban Tongmai Granules, thrombus length of blood stasis model rats in vitro reduced significantly (P<0.05-0.01),wet and dry weight of thrombus reduced significantly (P<0.05), the shear rate of the whole blood viscosity under 100 S~(-1), 30 S~(-1), 5 S~(-1) decreased significantly as well (P<0.05-0.01), and the shear rate of whole blood viscosity had decreasing tendency under 200 S~(-1).Conclusion Rongban Tongmai Granules can inhibit thrombosis and lower blood viscosity.

12.
J. huazhong univ. sci. tech. med. sci ; (6): 192-193,198, 2006.
Article in Chinese | WPRIM | ID: wpr-266417

ABSTRACT

The effects of fenofibrate on plasminogen activator inhibitor-1 (PAI-1) expression in human umbilical endothelial cell-derived transformed cell line-ECV 304 cells were investigated. ECV 304 cells were incubated with different concentrations of fenofibrate (0, 10, 50, 100 μmol/L) for 24 h. PAI-1 mRNA and protein was detected by reverse transcription-polymerase chain reaction (RT-PCR) and Westernblot respectively. PAI-1 antigenic content of endothelial cells was measured by using ELISA. Fenofibrate could inhibit the PAI-1 mRNA and protein expression and reduce PAI-1 antigenic content dependently. After treatment with fenofibrate (10 μmol/L), the expression levels of PAI-1 mRNA and protein were 0.65±0.05 and 0.96±0.11 respectively, significantly lower than in the control group (0.78±0.03 and 1.21±0.15, respectively, P<0.05). PAI-1 antigenie contents (24.52±8.39) in ECV304 cells treated with 10 μmol/L fenofibrate were significantly lower than those in the control group (6.98±5.12, P<0.05). It was concluded that fenofibrate inhibited the expression of PAI-1 mRNA in ECV304 cells, and reduce the protein expression and the antigenic content of PAI-1, suggesting that fenofibrate may have an antiatherosclerotic effect on endothelial cells by PAI-1 pathway.

13.
Article in English | WPRIM | ID: wpr-641021

ABSTRACT

The effects of fenofibrate on plasminogen activator inhibitor-1 (PAI-1) expression in human umbilical endothelial cell-derived transformed cell line--ECV 304 cells were investigated. ECV 304 cells were incubated with different concentrations of fenofibrate (0, 10, 50, 100 micromol/L) for 24 h. PAI-1 mRNA and protein was detected by reverse transcription-polymerase chain reaction (RT-PCR) and Western blot respectively. PAI-1 antigenic content of endothelial cells was measured by using ELISA. Fenofibrate could inhibit the PAI-1 mRNA and protein expression and reduce PAI-1 antigenic content dependently. After treatment with fenofibrate (10 micromol/L), the expression levels of PAI-1 mRNA and protein were 0.65 +/- 0.05 and 0.96 +/- 0.11 respectively, significantly lower than in the control group (0.78 +/- 0.03 and 1.21 +/- 0.15, respectively, P<0.05). PAI-1 antigenic contents (24.52 +/- 8.39) in ECV304 cells treated with 10 micromol/L fenofibrate were significantly lower than those in the control group (6.98 +/- 5.12, P<0.05). It was concluded that fenofibrate inhibited the expression of PAI-1 mRNA in ECV304 cells, and reduce the protein expression and the antigenic content of PAI-1, suggesting that fenofibrate may have an antiatherosclerotic effect on endothelial cells by PAI-1 pathway.

14.
Article in Chinese | WPRIM | ID: wpr-234510

ABSTRACT

In order to explore the molecular mechanism of arsenic trioxide treating multiple myeloma (MM) via inhibition of angiogenesis, the expression of brain derived neurotrophic factor (BD-NF) and its specific receptor TrkB in human MM cell line KM3 and endothelial cell line ECV304 was detected by Western blotting. The angiogenic activity was evaluated by wound migration assay and tubule formation assay in vitro. The results showed that BDNF was detected in the MM cells and TrkB in the endothelial cells. Furthermore, 100 ng/mL BDNF could significantly induced endo thelial cell tubule formation and wound migration. As2 O3 depressed the expression of BDNF and TrkB in the dose- and time-dependent manner. As2O3 inhibited BDNF-induced wound migration and capillary tube formation. It was concluded that BDNF is a novel angiogenic protein as well as VEGF and has a relation with the pathogenesis of MM. As2O3 interrupts a paracrine loop between MM cells and endothelial cells by down-regulating the TrkB expression in endothelial cells and inhibiting BDNF production in MM cells, finally resulting in inhibition of MM angiogenesis. This is probably one part of the mechanisms of the As2O3 treating MM via the inhibition of angiogenesis.

15.
Article in Chinese | WPRIM | ID: wpr-528860

ABSTRACT

AIM:To investigate the effects of brain-derived neurotrophic factor(BDNF)on extracellular proteolytic enzymes including matrix metalloproteinases(MMPs)and serine proteases,in particular,the urokinase-type plasminogen activator(uPA)-plasmin system in a human umbilical vein endothelial cell(HUVEC)model.METHODS:The HUVEC was activated with different doses of BDNF(25-200 ?g/L)for different time period(6-48 h).Reverse transcriptase-polymerase chain reaction(RT-PCR)was used to assay MMP-2,MMP-9,TIMP-1,and TIMP-2 mRNA in HUVEC.The cultured conditioned medium was analyzed for MMP and uPA activity by gelatin zymography and fibrin zymography,respectively.uPA,PAI-1,TIMP-1,and TIMP-2 were quantified by Western blotting analysis.RESULTS:The stimulation of serum-starved HUVECs with BDNF caused marked increase in MMP-2 and MMP-9 mRNA expression and induced the pro-MMP-2 and pro-MMP-9 activation without significant differences in proliferation.However,BDNF had no effect on TIMP-1 and TIMP-2 production.BDNF increased uPA and PAI-1 production in a dose dependent manner up to 100 ?g/L,while effects of 200 ?g/L were approximately equal to those of 100 ?g/L.BDNF stimulated uPA and PAI-1 production beyond that in control cultures from 12 h until 48 h after BDNF addition.Protease activity for uPA was also increased by BDNF in a dose dependent manner.CONCLUSION:BDNF activates MMP and uPA/PAI-1 proteolytic network in HUVEC.

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