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Objective:To explore the prediction model of tissue chip technology for the chemotherapy response of patients with colorectal cancer.Methods:217 patients with colorectal cancer who had received standardized chemotherapy in the Affiliated People’s Hospital of Ningbo University from Jan. 2017 to Dec. 2019 were prospectively selected. The patients were randomly divided into training set (152 cases) and test set (65 cases) according to the ratio of 7:3, and were followed up for 6 months. The clinical data of the patients in the training set were compared, the expression levels of Ang-2, caspase-3 and CD147 in the patients were analyzed by tissue microarray technology, and the related factors affecting the responsiveness of colorectal cancer chemotherapy were analyzed by the Logistic regression model. R software was used based on the training set. A nomogram prediction model was built and model performance on the test set was evaluated.Results:One case was excluded from the training center, and 151 cases were finally included, including 93 cases in the chemotherapy response group and 58 cases in the chemotherapy response group. The tumor diameter, serum carcinoembryonic antigen, caspase3, Ang2 expression level, and the proportion of clinical stage IV in the poor chemotherapy group were significantly higher than those in the good chemotherapy group (all P<0.05) ; Logistic regression showed tumor diameter ( OR=2.394), serum carcinoembryonic antigen ( OR=1.878), caspase-3 ( OR=4.261), Ang-2 expression level ( OR=5.457), and clinical stage IV ( OR=5.954) were independent risk factors for adverse drug reactions in patients with colorectal cancer (all P<0.05). The consistency index (C-index) for predicting the factors related to adverse chemotherapy reactions in patients with colorectal cancer was 0.915. External verification showed that the sensitivity was 86.96%, the specificity was 92.50%, and the accuracy was 90.48% (42/65) . Conclusion:The expression levels of Ang-2 and caspase-3 are correlated with the responsiveness of colorectal cancer to chemotherapy, and can be used as predictive indicators to evaluate the responsiveness of colorectal cancer to chemotherapy.
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Aim To develop an in vitro high throughput drug screening system based on reporter gene assay for identification of novel compounds with PXR, FXR and LXRα agonist activity. Methods The expressions of exogenous PXR, FXR and LXRαgene in HEK293, HepG2 and LS174T cells were examined by Real-Time quantity PCR. pSG5-hPXR and pGL3-XREM-CYP3A4, pEGFP-N3-hFXR and EcRE-TK-Luc, pCMX-FLAG-hLXRα and pGL3-XREM-CYP3A4 were cotransfected into cells and the optimal ratio of three plasmids was determined. The dose-response relationship between the positive drug and the fold induction was determined. The specificity of the model was ex-amined, and the repeatability was also determined by Z′ value. Results ① The PXR, FXR and LXRα mRNA expression in HEK293 cell is low among three different cells. ②reporter gene vector and expression plasmid ratio of 1∶ 1, 2∶ 1 and 2∶ 1 were proved to be suitable for highest relative luciferase activity for PXR, FXR or LXRα agonist screening model. ③ The relative luciferase activity was induced by Rif, CDCA or T0901317 in a dose-dependent manner. ④Only Rif, CDCA or T0901317 could significantly increase the relative luciferase activity in PXR,FXR or LXRα agonist screening model, no effect of other nuclear re-ceptors agonist was observed, and the values of Z′-factor for PXR, FXR and LXRαagonist screening model were 0. 58, 0. 66 and 0. 63, respectively. Conclusion An in vitro PXR, FXR and LXRα agonist high-throughput screening models are devel-oped with acceptable specificity and repeatability, and the mod-els can be used to screen PXR, FXR and LXRα agonist.
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ObjectiveTo investigate the expression of miR-21 in diffuse large B cell lymphoma (DLBCL)and normal lymph tissues and its potential relevance with clinicopathological characteristics.MethodsThe expression levels of miR-21 in 50 primary DLBCL and 12 normal lymph node tissue specimens were examined by TaqMan real-time polymerase chain reaction.The expression of bcl-2 and p53 was detected by immunohistochemistry staining. ResultsThe expression of miR-21 was significantly higher in tumor tissues than that in normal tissues, in GCB subtypes higher than in non-GCB subtypes. And it was negatively correlated with bcl-2(P=0.020),while positively correlated with p53(P=0.022). Up-regulated miR-21 expression was low in three years of survival rate. ConclusionMiR-21 may indicate a more aggressive phenotype and serve as a molecular prognostic marker in DLBCL. High-expression of miR-21 is a key feature that is correlated with cell proliferation in DLBCL.miR-21 may have some guiding significance in prognosis.bcl-2,p53 is possibly one of the targets of miR-21 in DLBCL.
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Objective To establish a high-performance liquid chromatography method for simultaneous determination of mycophenolic acid(MPA) and its 7-O-glucuronide metabolite (MPAG) in human plasma and to study pharmacokinetics of MPA in Chinese renal transplant recipients after administration of mycophenolate mofetil( MMF). Methods Plasma protein was precipitated with metlianol: 5% ZnSO4 ( 70∶30, V∶ V), using naproxen as internal MPA and MPAG after 1.5g/d administration of MMF in 6 early-stage renal transplant recipients were as follows :Tmax was(1.08±0.74)h and(2.58±1.24)h,Cmax was(21.33±8.61)mg/L and(106.98±31.91)mg/L,AUCO-t was (58.73 ±16.26)mg ? L-1 ? h-1 and(833.32±215.03)mg ? L-1 ? h-1,respectively.Conclusion This method was accurate, sensitive and specific and it was successfully applied in therapeutic drug monitoring (TDM) of mycophenolate mofetil in early-stage renal transplant recipients.
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Objectives To explore the expression of HER4 and VEGF in NSCLC and elucidate the relationship between their expression and the characteristic of clinical pathology. Methods 82 cases of paraffin-embedded tissues from informative NSCLC were used to detect the expression of HER4 and VEGF by means of immunohistochemical assay. Results HER4 is overexpressed in 65;9%of NSCLC cases. The overexpression of HER4 is correlated with the lymph node metastasis and TNM staging. VEGF is expressed in 53.7%of NSCLC cases. The expression of VEGF is also correlated with the lymph node metastasis and TNM staging, and the expression of VEGF is correlated with the overexpression of HER4.Conclusions HER4 and VEGF are the protein to regulate the growth of NSCLC and it might be a good way for the treatment of NSCLC by suppressing the overexpression of HER4 and VEGF.
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OBJECTIVE:To study the pharmacokinetics and bioequivalence of both domestic ranitidine hydrochloride capsules and imported ranitidine hydrochloride tablets.METHODS:20healthy volunteers were randomized into groups,whose plasma concentrations of ranitidine were determined at different time after single oral dose of300mg ranitidine hydrochloride capsule or ranitidine hydrochloride tablets300mg by own control by a RP-HPLC method,the pharmacokinetic parameters were computed and which were experienced variance analysis and two-way t-tests and one-way t-tests.RESULTS:The respective pharmacokinetic parameters of ranitidine hydrochloride tablets and ranitidine hydrochloride capsuless were as fol?lows,the C max were(1247.1?547.5)?g/L and(1294.8?613.2)?g/L;t max were(2.98?0.73)h and(2.73?0.80)h;t 1/2 were(3.17?0.36)h and(3.33?0.42)h;AUC 0～t were(5805.9?1403.5)(?g?h)/L and(5941.2?1526.3)(?g?h)/L;AUC 0～∞ were(6163.8?1456.4)(?g?h)/L and(6351.8?1652.7)(?g?h)/L;The relative bioavailability of the ranitidine hydrochloride capsules to ranitidine hydrochloride tablets was(104.3?24.3)%.CONCLUSION:Ranitidine hydrochloride capsules and the ranitidine hydrochloride tablets were bioequivalent.
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When we did compatibility testing, we found a case of leukemia with irregular antibody. The antibody specificity was identified as anti-Ce using panel-cell, and was IgG antibody. The anti-Ce antibody had both anti-C and anti-e activity. It is very difficult to find a Ce antigen negative blood for transfusion. The compatible donors rate is very low, only 2%-3%.
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OBJECTIVE:To study the pharmacokinetics of two kinds of famotidine capsule from different factories in healthy volunteers and to evaluate the bioavailability of them METHODS:A single oral 40 mg dose of famotidine capsule of reference or test preparation was given to healthy male volunteers according to an open randomized crossover study The plasma concentrations of famotidine were determined by a RP-HPLC method The pharmacokinetic parameters and bioavailability of test preparation were compared with reference preparation RESULTS:The main pharmacokinetic parameters of the reference preparation and the test preparation were as follows:Cmax were(189 9?72 1)?g/L and(170 1?59 6)?g/L;Tmax were(2 5?0 8)h and (2 1?0 8)h;T1/2 were(4 1?0 9)h and(3 8?0 8)h;AUC0～t were (1 031 7?316 7)?g/(L?h)and(1 019 4?290 5)?g/(L?h);AUC0→∞ were(1 123 9?346 0)?g/(L?h)and(1 103 4?312 0)?g/(L?h);The relative bioavailability of reference to test preparation was(101 6?22 6)% CONCLUSION:The results showed that the reference preparation and the test preparation were bioequivalent
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Purpose To explore the clinicopathological features of subcutaneous panniculitic T-cell lymphoma(SPTCL) and significances of genetic analysis in the diagnosis. Methods Histopathology, immunohistochemitry and detection of clonal gene rearrangement by PCR were used in 3 cases of subcutaneous panniculitic T-cell lymphoma (SPTCL), which were originally diagnosed as relapsing nodular nonsuppurative panniculitis. Results Three misdiagnostic cases were correctly redefined as subcutaneous panniculitic T-cell lymphoma, with immunophenotype of CD45+,CD45RO+, Mac387－,and clonal TCR-β gene rearrangement. Conclusions Subcutaneous panniculitic T-cell lymphoma has distinctive clinicopathological features. Genetic analysis is an effective method for the diagnosis of SPTCL.