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Objective:To investigate the incidences of metachronous advanced adenoma (MAA) in patients with simultaneous multiple primary colorectal cancer (CRC) and patients with sporadic CRC.Methods:From January 1, 2008 to September 30, 2022, at Beijing Shijitan Hospital, Capital Medical University, CRC patients who underwent surgery and 3 years follow-up with endoscopy were enrolled. The patients completed colonoscopy at least 2 times during follow-up in 6 to 36 months after surgery, and the interval between the 2 times colonoscopies was over 6 months. Clinical data including age, gender, and tumor location, stage, pathological features, combined underlying diseases, preoperative carcinoembryonic antigen, hemoglobin and other laboratory results, baseline colonoscopy results, and detection of MAA were collected. According to age (±2 years old), gender, location of primary lesion and stage of tumor, patients with simultaneous CRC or sporadic CRC were matched at 1∶1 ratio by propensity score matching. The cumulative risks of MAA in patients with simultaneous multiple primary CRC and patients with sporadic CRC were calculated. Cox proportional hazard regression was used to analyze the influencing factors in the occurrence of MAA.Results:A total of 814 CRC patients were enrolled and matched. After paired matching, there were 36 cases of simultaneous multiple primary CRC (78 lesions) and 78 cases of sporadic CRC (78 lesions). The cumulative incidences of MAA at 1, 2 and 3 years of simultaneous CRC group were 11.1%(4/36), 22.2%(8/36) and 33.3%(12/36), respectively. The cumulative incidences of MAA at 1-, 2- and 3-year of sporadic CRC group were 3.8%(3/78), 12.8%(10/78) and 20.5%(16/78), respectively.Simultaneous CRC was correlated with an increase in the 3-year cumulative incidence of MAA ( HR=4.163, 95% confidence interval(95% CI) 1.032 to 4.721, P=0.047). Especially in left-sided CRC, the risk of MAA in simultaneous CRC increased ( HR=7.186, 95% CI 1.602 to 20.787, P=0.010). The results of multivariate cox-regression analysis indicated that detection of simultaneous advanced adenoma at baseline endoscopy was an independent risk factor of MAA ( HR=3.175, 95% CI 1.411 to 7.142, P=0.005). Conclusion:Colouoscopy follow-up should be strengthened in patients with simultaneous multiple primary CRC and simultaneous advanced adenomas.
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Objective To investigate the value of Baveno Ⅶ criteria versus Expanded Baveno Ⅶ criteria in screening for high-risk varices (HRV) in patients with compensated advanced chronic liver disease (cACLD). Methods A total of 146 patients with cACLD who were admitted to Beijing Shijitan Hospital, Capital Medical University, from January 2016 to December 2018 were enrolled, and according to the absence or presence of HRV based on gastroscopy, they were divided into HRV group with 68 patients and control group with 78 patients. Clinical data, liver stiffness measurement (LSM), and gastroscopy findings were analyzed, and different Baveno Ⅶ criteria were analyzed in terms of their sensitivity and specificity in the diagnosis of HRV. The Mann-Whitney U test and the McNemar test were used for comparison of continuous data between groups, and the chi-square test was used for comparison of categorical data between groups. A univariate logistic regression analysis was performed for the variables used to predict HRV, and a multivariate analysis was performed for the variables with P 20 kPa or PLT 25 kPa or PLT < 110×10 9 /L was associated with HRV (both P < 0.05). LSM and PLT had an area under the ROC curve of 0.797 (95% confidence interval [ CI ]: 0.723-0.859) and 0.789 (95% CI : 0.714-0.852), respectively, in the diagnosis of HRV. There were significant differences in the prevalence rates of esophageal and gastric varices and HRV between the patients who met Baveno Ⅶ criteria and those who did not meet such criteria ( χ 2 =23.14 and 23.14, both P < 0.001), as well as between the patients who met Expanded Baveno Ⅶ criteria and those who did not meet such criteria ( χ 2 =43.51 and 25.71, both P < 0.001). Although a higher proportion of patients were exempted from gastroscopy based on Expanded Baveno Ⅶ criteria (32.9% vs 13.7%), Baveno Ⅶ criteria had higher sensitivity (0.98 vs 0.88) and negative predictive value (0.95 vs 0.83) and could better avoid the missed diagnosis of HRV (1.0% vs 9.3%). Conclusion Baveno Ⅶ criteria are more suitable for the screening for HRV in cACLD patients in China.
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Objective:To explore whether the regular feedback system in opportunistic screening of colorectal cancer can improve the adenoma detection rate (ADR) of endoscopists.Methods:This study was an observational study, divided into three stages: the baseline stage before intervention (the pre-intervention period), the regular feedback stage (the intervention period) and the post-intervention stage (the post-intervention period). In the pre-intervention period, all patients who underwent opportunistic screening of colorectal cancer in Department of Gastroenterology in Beijing Shijitan Hospital Affiliated to Capital Medical University from June 2017 to May 2018 were reviewed, and the ADR of each endoscopist was calculated. In the intervention period from June 2018 to November 2018, colonoscopies were performed on patients for opportunistic screening of colorectal cancer by endoscopists who participated in the feedback. The ADR of each endoscopist during the previous month was calculated at the beginning of each month and feedback was provided in the form of a report. In the post-intervention period from December 2018 to January 2019, colonoscopies were performed on patients for opportunistic screening of colorectal cancer by endoscopists who participated in the feedback. The ADR of each endoscopist was calculated after the feedback stopped. ADR and polyp detection rate (PDR) of three stages were compared.Results:A total of 1 768, 1 308 and 344 patients were enrolled for opportunistic screening of colorectal cancer during the pre-intervention, the intervention and the post-intervention period respectively. Eight endoscopists participated in the whole process of this study. The total ADR increased from 23.70% (419/1 768) in the pre-intervention period to 33.72% (441/1 308) in the intervention period ( χ2=37.449, P<0.05). Two months after intervention, ADR decreased slightly to 33.14% (114/344), but was still higher compared with before ( χ2=13.602, P<0.05). The total PDR increased from 47.17% (834/1 768) in the pre-intervention period to 52.68% (689/1 308) in the intervention period ( χ2=9.111, P<0.05). Two months after the intervention, PDR increased slightly to 53.78% (185/344), and still higher compared with before ( χ2=5.035, P<0.05). Conclusion:Regular feedback to endoscopists can improve ADR in opportunistic screening of colorectal cancer.
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Objective@#To investigate clinicopathological characteristics, diagnosis and treatment of multiple primary colorectal carcinoma (MPCC).@*Methods@#From January 2008 to March 2017, 42 patients diagnosed with MPCC underwent surgery at Beijing Shijitan Hospital, Capital Medical University. Their clinicopathological features, diagnosis and treatment were analyzed.@*Results@#These 42 MPCC patients accounted for 7.1% (42/592) colorectal cancer patients in the same period. There were 64 intestinal cancer lesions in 32 patients (76.2%) with synchronous carcinoma (SC), and 20 intestinal cancer lesions in 10 patients (23.8%) with metachronous carcinoma(MC), where the interval between the first and the recurrent was 18-105 months. The proportion of patients in the SC group with highly to moderately differentiated adenocarcinoma was significantly higher compared with that of the MC group (P<0.05), while the incidence of mucinous carcinoma was lower than that of the MC group(P<0.05). No significant differences were found with regard to tumor size, location, complications with adenoma, TNM stages, lymph nodes metastases or DNA mismatch repair between the SC group and the MC group(all P>0.05). Among 42 patients undergoing radical operation, 6 received colonic metallic stent implantation as a bridge to elective resection in 10 patients with colonic obstruction.@*Conclusion@#MPCC, mainly two-lesion cancer, is most commonly found in sigmoid colon and rectum. Those with poorly differentiated cancer, mucinous carcinoma and those complicated with adenoma should be closely followed up with colonoscopy. Colonic metallic stent implantation as a bridge to elective resection may improve the detection rate of SC.
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Objective@#To investigate the factors related to severe acute pancreatitis (SAP) with intestine functional disturbance (IFD) and to establish the multiple predictor models of SAP with IFD.@*Methods@#Clinical data of consecutive SAP patients admitted to department of gastroenterology of Beijing Shijitan Hospital, Capital Medical University from January 2015 to March 2019 were retrospectively collected and analyzed. According to the occurrence of IFD at 48 hours after onset, the patients were divided into IFD group and control group. The clinical indicators within 4 hours after admission were compared between the two groups, and the independent predictive factors for SAP with IFD were screened by single factor analysis and multiple classified Logistic regression analysis. The unweighted predictive score (unwScore) and weighted predictive score (wScore) models were constructed by combining the independent predictors. The receiver operating characteristic (ROC) curves of SAP patients with IFD were plotted by independent predictive factors and predictive models, and the clinical predictive effect of each independent predictive index and predictive models were analyzed.@*Results@#A total of 149 patients with SAP were enrolled, including 87 males and 62 females, with age of (52.8±18.1) years old. There were 45 patients in IFD group and 104 patients in control group.Univariate analysis and multiple classified Logistic regression analysis showed that high sensitive C-reactive protein (hs-CRP), blood urea nitrogen (BUN), serum creatinine (SCr), serum calcium (Ca), procalcitonin (PCT) and neutrophil-lymphocyte ratio (NLR) were independent predictive factors of SAP with IFD. The ROC curve was used to calculate the cut-off value of the above indexes to predict IFD, and unwScore model was established. The cut-off score of IFD prediction by the unwScore model was 3 points, and the probability of IFD increased with the increase of the score. The area under ROC curve (AUC) of unwScore was 0.944, the sensitivity was 95.6%, the specificity was 94.2%, the positive predictive value (PPV) was 87.8%, and the negative predictive value (NPV) was 98.0%. The binary Logistic regression analysis of hs-CRP, BUN, Ca, SCr, PCT and NLR were carried out, and wScore model was established. The AUC of wScore was 0.959, the sensitivity was 95.9%, the specificity was 96.2%, the PPV was 91.5%, and the NPV was 98.1%; predictive value was superior to each independent index and unwScore model.@*Conclusions@#hs-CRP, BUN, SCr, Ca, PCT and NLR were independent predictive factors of SAP with IFD. The multiple predictor models of SAP with IFD have a good predictive efficiency which may provide valuable clinical reference for prediction and treatment.
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Objective To investigate clinicopathological characteristics,diagnosis and treatment of multiple primary colorectal carcinoma (MPCC). Methods From January 2008 to March 2017,42 patients diagnosed with MPCC underwent surgery at Beijing Shijitan Hospital,Capital Medical University. Their clinicopathological features,diagnosis and treatment were analyzed. Results These 42 MPCC patients accounted for 7. 1％ (42/ 592)colorectal cancer patients in the same period. There were 64 intestinal cancer lesions in 32 patients (76. 2％)with synchronous carcinoma (SC),and 20 intestinal cancer lesions in 10 patients (23. 8％)with metachronous carcinoma(MC),where the interval between the first and the recurrent was 18-105 months. The proportion of patients in the SC group with highly to moderately differentiated adenocarcinoma was significantly higher compared with that of the MC group (P<0. 05),while the incidence of mucinous carcinoma was lower than that of the MC group(P<0. 05). No significant differences were found with regard to tumor size,location,complications with adenoma,TNM stages,lymph nodes metastases or DNA mismatch repair between the SC group and the MC group(all P>0. 05). Among 42 patients undergoing radical operation,6 received colonic metallic stent implantation as a bridge to elective resection in 10 patients with colonic obstruction. Conclusion MPCC,mainly two-lesion cancer,is most commonly found in sigmoid colon and rectum. Those with poorly differentiated cancer, mucinous carcinoma and those complicated with adenoma should be closely followed up with colonoscopy. Colonic metallic stent implantation as a bridge to elective resection may improve the detection rate of SC.
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Objective To investigate the factors related to severe acute pancreatitis (SAP) with intestine functional disturbance (IFD) and to establish the multiple predictor models of SAP with IFD. Methods Clinical data of consecutive SAP patients admitted to department of gastroenterology of Beijing Shijitan Hospital, Capital Medical University from January 2015 to March 2019 were retrospectively collected and analyzed. According to the occurrence of IFD at 48 hours after onset, the patients were divided into IFD group and control group. The clinical indicators within 4 hours after admission were compared between the two groups, and the independent predictive factors for SAP with IFD were screened by single factor analysis and multiple classified Logistic regression analysis. The unweighted predictive score (unwScore) and weighted predictive score (wScore) models were constructed by combining the independent predictors. The receiver operating characteristic (ROC) curves of SAP patients with IFD were plotted by independent predictive factors and predictive models, and the clinical predictive effect of each independent predictive index and predictive models were analyzed. Results A total of 149 patients with SAP were enrolled, including 87 males and 62 females, with age of (52.8±18.1) years old. There were 45 patients in IFD group and 104 patients in control group. Univariate analysis and multiple classified Logistic regression analysis showed that high sensitive C-reactive protein (hs-CRP), blood urea nitrogen (BUN), serum creatinine (SCr), serum calcium (Ca), procalcitonin (PCT) and neutrophil-lymphocyte ratio (NLR) were independent predictive factors of SAP with IFD. The ROC curve was used to calculate the cut-off value of the above indexes to predict IFD, and unwScore model was established. The cut-off score of IFD prediction by the unwScore model was 3 points, and the probability of IFD increased with the increase of the score. The area under ROC curve (AUC) of unwScore was 0.944, the sensitivity was 95.6%, the specificity was 94.2%, the positive predictive value (PPV) was 87.8%, and the negative predictive value (NPV) was 98.0%. The binary Logistic regression analysis of hs-CRP, BUN, Ca, SCr, PCT and NLR were carried out, and wScore model was established. The AUC of wScore was 0.959, the sensitivity was 95.9%, the specificity was 96.2%, the PPV was 91.5%, and the NPV was 98.1%;predictive value was superior to each independent index and unwScore model. Conclusions hs-CRP, BUN, SCr, Ca, PCT and NLR were independent predictive factors of SAP with IFD. The multiple predictor models of SAP with IFD have a good predictive efficiency which may provide valuable clinical reference for prediction and treatment.
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Objective To investigate the factors related to severe acute pancreatitis (SAP) with intestine functional disturbance (IFD) and to establish the multiple predictor models of SAP with IFD. Methods Clinical data of consecutive SAP patients admitted to department of gastroenterology of Beijing Shijitan Hospital, Capital Medical University from January 2015 to March 2019 were retrospectively collected and analyzed. According to the occurrence of IFD at 48 hours after onset, the patients were divided into IFD group and control group. The clinical indicators within 4 hours after admission were compared between the two groups, and the independent predictive factors for SAP with IFD were screened by single factor analysis and multiple classified Logistic regression analysis. The unweighted predictive score (unwScore) and weighted predictive score (wScore) models were constructed by combining the independent predictors. The receiver operating characteristic (ROC) curves of SAP patients with IFD were plotted by independent predictive factors and predictive models, and the clinical predictive effect of each independent predictive index and predictive models were analyzed. Results A total of 149 patients with SAP were enrolled, including 87 males and 62 females, with age of (52.8±18.1) years old. There were 45 patients in IFD group and 104 patients in control group. Univariate analysis and multiple classified Logistic regression analysis showed that high sensitive C-reactive protein (hs-CRP), blood urea nitrogen (BUN), serum creatinine (SCr), serum calcium (Ca), procalcitonin (PCT) and neutrophil-lymphocyte ratio (NLR) were independent predictive factors of SAP with IFD. The ROC curve was used to calculate the cut-off value of the above indexes to predict IFD, and unwScore model was established. The cut-off score of IFD prediction by the unwScore model was 3 points, and the probability of IFD increased with the increase of the score. The area under ROC curve (AUC) of unwScore was 0.944, the sensitivity was 95.6%, the specificity was 94.2%, the positive predictive value (PPV) was 87.8%, and the negative predictive value (NPV) was 98.0%. The binary Logistic regression analysis of hs-CRP, BUN, Ca, SCr, PCT and NLR were carried out, and wScore model was established. The AUC of wScore was 0.959, the sensitivity was 95.9%, the specificity was 96.2%, the PPV was 91.5%, and the NPV was 98.1%;predictive value was superior to each independent index and unwScore model. Conclusions hs-CRP, BUN, SCr, Ca, PCT and NLR were independent predictive factors of SAP with IFD. The multiple predictor models of SAP with IFD have a good predictive efficiency which may provide valuable clinical reference for prediction and treatment.
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Objective: To examine endoscopic features of early colorectal carcinomas smaller than 2 cm. Methods: A total of 191 pa-tients (201 early colorectal carcinomas) who were definitely diagnosed with early colorectal cancer smaller than 2 cm between Janu-ary 2014 and December 2017 in Beijing Shijitan Hospital, Capital Medical University were enrolled. The patients'clinical characteris-tics, endoscopic and pathological data were retrospectively analyzed. Results: There were more male patients than female patients (1.81:1) in the study population; distribution of lesions was higher in the left colon than in the right colon (141/201). Group 1 had a higher number of IIa lesions (20/67, P=0.037) and a lower number of Ip lesions than Group 2 (52/134, P<0.01). Conclusions: There are special characteristics in distribution and endoscopic manifestations of early colorectal carcinoma. Lesion size was less than 1 cm in 67 (191 cases of early colorectal cancer) early colorectal carcinoma cases; however, a high-risk adenoma is defined as a lesion larger than 1 cm in size. Therefore, regardless of lesion size, if fractionation, echinodermata, congestion, erosion, expansion, and depression are observed, the lesion should be assessed in detail for the sake of carcinogenesis.
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<p><b>OBJECTIVE</b>To investigate the expression of vascular endothelial growth factor (VEGF) of human multiple myeloma (MM) cell line RPMI8226 regulated by brain-derived neurotrophic factor (BDNF), and preliminarily approach the close relationship between BDNF and angiogenesis of MM.</p><p><b>METHODS</b>The recombinant eukaryotic BDNF siRNA expression vector was designed and constructed. The empty vector pGenesil-1, and the recombinant plasmid, pGenesil-shRNA-BDNF were transfected into RPMI8226 cells using Lipofectamine™ 2000 (groups P0 and P1, respectively). BDNF mRNA and protein level in RPMI8226 cells were detected by RT-PCR and Western blotting, respectively; the cellular proliferation activity was determined by MTT assay, while the cell apoptosis was measured by flow cytometry; the variation of VEGF mRNA level in RPMI8226 cells via transfection was determined by RT-PCR, the secretion of VEGF was detected by ELISA.</p><p><b>RESULTS</b>(1)The recombinant eukaryotic BDNF siRNA expression vectors were successfully constructed. BDNF mRNA expression and protein level in P1 group were significantly inhibited compared to those in non-transfected group (Pn) and P0 groups (P<0.05); (2)MTT tests demonstrated that the cellular proliferation activities were obviously decreased in Pn (0.42 ± 0.06) vs P0 (0.56 ± 0.06) and P1 (0.50 ± 0.04) groups (P<0.05); (3)The early cell apoptosis rates were statistically increased in P1 [(53.84 ± 9.95)%] vs Pn [(5.23 ± 2.46)%] and P0 [(9.10 ± 3.46)%] groups (P<0.01); (4)The silence of endogenous BDNF significantly decreased the expression of VEGF in RPMI8226 cells:the relative expression level of VEGF121, VEGF145 and VEGF165 in P1 group were (0.62 ± 0.07), (0.47 ± 0.09) and (0.57 ± 0.02) folds compared to Pn group (P<0.05); (5)ELISA demonstrated that secretion of VEGF in P1 group were (0.36 ± 0.05) and (0.44 ± 0.06) folds compared to Pn and P0 group, respectively (P<0.05).</p><p><b>CONCLUSION</b>BDNF gene silence can obviously increase apoptosis of RPMI8226 cells, inhibit their proliferation and decrease the expression of VEGF. BDNF might mediate the expression of VEGF in MM cells, which may be involved in MM angiogenesis.</p>
Subject(s)
Humans , Apoptosis , Brain-Derived Neurotrophic Factor , Cell Line, Tumor , Gene Silencing , Genetic Vectors , Multiple Myeloma , Neovascularization, Pathologic , RNA, Messenger , RNA, Small Interfering , Transfection , Vascular Endothelial Growth Factor AABSTRACT
In this study, we administered a modified schedule of weekly intravenous Bortezomib at 1.6 mg/m(2) with dexamethasone (BD) and compared it to the standard 1.3 mg/m(2) twice-weekly BD regimen in Chinese patients with newly diagnosed multiple myeloma (MM). We assessed the difference in efficacy, safety profile and survival between the once-weekly and twice-weekly cohorts (13 vs. 24 patients). The over response rate was similar with both arms of the study, being 77% in the once-weekly schedule and 74.9% in the twice-weekly schedule (P=0.690). The median overall survival was not reached in either schedule. Also, the median progression-free survival and duration of response of the once-weekly schedule did not significantly differ from those of the twice-weekly schedule (8 months vs.10 months, P=0.545 and 6 months vs.7 months, P=0.467 respectively). Peripheral sensory neuropathy and grade 3/4 hematologic toxic effects were more frequently reported in the twice-weekly schedule than the once-weekly schedule, but there was no statistically significant difference. This preliminary experience in Chinese patients with newly diagnosed MM indicated that once-weekly infusion of Bortezomib plus dexamethasone may improve safety without affecting outcome.
Subject(s)
Adult , Aged , Female , Humans , Male , Middle Aged , Boronic Acids , Bortezomib , Dexamethasone , Multiple Myeloma , Drug Therapy , PyrazinesABSTRACT
In this study, we administered a modified schedule of weekly intravenous Bortezomib at 1.6 mg/m(2) with dexamethasone (BD) and compared it to the standard 1.3 mg/m(2) twice-weekly BD regimen in Chinese patients with newly diagnosed multiple myeloma (MM). We assessed the difference in efficacy, safety profile and survival between the once-weekly and twice-weekly cohorts (13 vs. 24 patients). The over response rate was similar with both arms of the study, being 77% in the once-weekly schedule and 74.9% in the twice-weekly schedule (P=0.690). The median overall survival was not reached in either schedule. Also, the median progression-free survival and duration of response of the once-weekly schedule did not significantly differ from those of the twice-weekly schedule (8 months vs.10 months, P=0.545 and 6 months vs.7 months, P=0.467 respectively). Peripheral sensory neuropathy and grade 3/4 hematologic toxic effects were more frequently reported in the twice-weekly schedule than the once-weekly schedule, but there was no statistically significant difference. This preliminary experience in Chinese patients with newly diagnosed MM indicated that once-weekly infusion of Bortezomib plus dexamethasone may improve safety without affecting outcome.
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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.
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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.
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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.
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AIM: To study the expression of tissue factor (TF) in cerebral microvascular thrombosis and its dynamic changes in rats. METHODS: 50 female SD rats were randomized to control group, 2, 4, 6, and 24 hours after thrombosis groups, 10 rats in each group. The model of cerebral microvascular thrombosis was induced by photo-chemical method. ELISA and immunohistochemistry methods were used to observe the changes of TF contents in blood plasma and the expression of TF in cerebral microvascular in each group. RESULTS: Cerebral thrombosis was induced by photo-chemical method successfully. The TF content in plasma was obviously higher in 4 h and 6 h groups than that in control group (P
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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.