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@#To investigate the influential mechanism of total flavonoids from Abelmoschus Manihot (HKZ) on cytochrome P450 (CYP450) isoforms in human liver microsomes and to verify its effect on the most significantly inhibited subtype CYP2C9 in rats.The inhibitory effects of HKZ on human CYP3A4, CYP2C9, CYP2C19, CYP2E1, CYP1A2 and CYP2D6 were evaluated through the cocktail method using ultra-performance liquid chromatography tandem mass spectrometry, then its inhibitory mechanism was investigated and kinetic parameters of enzyme inhibition were calculated By comparing the pharmacokinetic behaviors of tolbutamide after single or multiple administration of 200 mg/kg HKZ and equal dose of CMC-Na in rats, the effects of HKZ on CYP2C11 enzyme (CYP2C9 isoenzyme) was estimated.The results indicated the significant inhibitory effect of HKZ on CYP2C9 and CYP2E1 with IC50 of 3.22 and 8.64 μg/mL, respectively. Also, it showed certain inhibitory ability on other isoforms with IC50 of 20-30 μg/mL.As demonstrated, HKZ may not be a time-dependent inhibitor which competitively inhibited CYP2E1 and CYP2C9 with Ki of 3.84 and 6.33 μg/mL.In contrast, it showed noncompetitive inhibition on CYP3A4 mediated testosterone-6β-hydroxylation and midazolam-4-hydroxylation reaction with Ki of 7.37 and 3.32 μg/mL.It was also a noncompetitive inhibitor of CYP1A2, CYP2D6 and CYPC219 with Ki values of 8.66, 11.49 and 21.94 μg/mL. HKZ did not change the pharmacokinetic parameters of CYP2C11 probe substrate tolbutamide in rat, but it affected the AUC0-t, cmax of 4-hydroxytolubutamide (P < 0.05). Therefore, drug-drug interaction mediated by CYP450 should be considered in clinical study.
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Writing and publishing biomedical research papers in English for academic purposes (EAP) has become an essential requirement for medical postgraduates in China. To face this challenge, medical postgraduates need adapt themselves to the local environment of English as a second language and the transformation from writing for examinations to writing for application. This change determines the features of biomedical research papers, including being application-oriented, using clear and concise language, organizing the discourse by specific genre rules, and assessing the quality according to the completion of communicative purposes. Based on these features, students can exploit the learning strategies of choosing a word suited for the style, structuring a sentence according to the logic, creating a paragraph of continuity and one main idea, and composing the discourse in line with the genre. These strategies may help medical postgraduates effectively improve their ability to write biomedical research papers in English.
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@#To establish a quantitative LC-MS/MS method for the simultaneous detection of components of Erlong Zuoci Pill in rat plasma: verbascoside, oxypaeoniflorin, echinacoside and benzoylpaeoniflorin, and to evaluate the pharmacokinetic characteristics of Erlong Zuoci Pill in rats, plasma samples were purified by protein precipitation using methanol as a protein precipitant.Methanol was used as the organic phase and aqueous solution containing 0.1% formic acid was used as the water phase.The quantitative analysis method of verbascoside, oxypaeoniflorin, echinacoside and benzoylpaeoniflorin was established in negative ion mode, and the validation of bioanalytical method was carried out.Healthy SD rats were selected, and 20 mL/kg (equivalent to the original drug 10 g/kg dose) of Erlong Zuoci Pill extract was administered by intragastric administration.The plasma concentration of the target compounds at different time intervals after administration was determined using the established method, and the pharmacokinetic parameters was calculated by the Phoenix WinNonlin8.3 software using the non-compartmental model.The method validation results showed that verbascoside (r = 0.993 7) and oxypaeoniflorin (r = 0.994 6) had good linear relationship in the concentration range of 0.5-50 ng/mL, echinacoside (r = 0.993 6) and benzoylpaeoniflorin (r = 0.992 6) had good linear relationship in the concentration range of 1-100 ng/mL.The relative standard deviations of the inter- and intra- batch precision of the four compounds were all less than 15%, and the inter- batch and intra- accuracies were between 85% and 115%.Extraction recovery, matrix effect and stability met the relevant requirements.After a single gavage of Erlong Zuoci Pill extract in rats, all the four compounds were rapidly absorbed and eliminated.Oxypaeoniflorin, echinacoside, and benzoylpaeoniflorin showed two peaks in their drug concentration-time curves.Compared with the other three compounds, oxypaeoniflorin has the highest concentration in rat plasma with cmax1 of (24.40 ± 4.78) ng/mL and cmax2 of (22.50 ± 2.70) ng/mL. The results show that the validation results of this method are in line with the guiding principles of biological sample analysis methods, and it can be used to evaluate the pharmacokinetic characteristics of Erlong Zuoci Pill extract in rats.
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After in-depth needs analysis, we combined our previously written textbook with digitalized platform by information technology, and proposed construction principles guided by English for academic purposes (EAP) theories. Through scientific design and ongoing modification, we finally developed an open online digital course with academic and practical properties. The course received positive feedback after release online. It may become an effective way to improve research paper writing skills for medical postgraduates and provide references for medical colleges to develop other EAP digital courses.
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@#The effect of sodium salicylate on the endogenous metabolism of hair cell-like cells (HEI-OC1).of mice was analyzed based on liquid chromatography-quadrupole time of flight mass spectrometry (LC-Q-TOF/MS).Firstly, HEI-OC1 cells were treated with different concentrations of sodium salicylate, and cell survival was examined by the CCK-8 method. Next, sodium salicylate was administered for different duration to observe the changes in cell morphology. Inter-group differential metabolites were screened out, and the associated metabolic pathways were analyzed based on metabonomic technology.Results showed that sodium salicylate could significantly inhibit the survival rate of HEI-OC1 cells, and that, as the concentration increased, the inhibitory effect became stronger. Also, the cell morphology could be elongated after administration and return to normal after withdrawal.Eighteen differential metabolites such as orotic acid, uridine and aspartic acid were screened out after treatment of sodium salicylate, which mainly involving two possible metabolic pathways, namely the metabolism of alanine, aspartic acid and glutamic acid, and that of pyrimidine.In summary, the application of metabolomics technology to evaluate the effect of sodium salicylate on hair cells from the microscopic perspective can provide new ideas for the study of sodium salicylate ototoxicity and development of tinnitus.
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Anaplastic lymphoma kinase (ALK) fusion gene, as a tumor driver gene, was crucial for the occurrence and development of non-small cell lung cancer (NSCLC). Recently, targeted ALK fusion gene has become the main treatment method for ALK-positive NSCLC. The first and second generation ALK inhibitors (ALKi), such as crizotinib, ceritinib, alectinib and ensartinib have been approved in China. However, there was no guidance for the management of ALKi adverse reactions. Therefore, this "Recommendations from experts in the management of adverse reactions to ALK inhibitors (2021 version)" has been summarized, led by Lung Cancer Professional Committee of Sichuan Cancer Society and Sichuan Medical Quality Control Center for Tumor Diseases, to provide practical and feasible strategies for clinical ALKi management specification of adverse reactions. .
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Humans , Carcinoma, Non-Small-Cell Lung , Crizotinib , Lung Neoplasms/genetics , Protein Kinase Inhibitors/adverse effects , Receptor Protein-Tyrosine Kinases/antagonists & inhibitorsABSTRACT
Radiotherapy is the most common treatment for nasopharyngeal carcinoma, and the radiotherapy technique is essential for the prognosis of nasopharyngeal carcinoma. Due to the complexity of the structure of the intensity-modulated device and the accuracy of the clinical requirements of radiotherapy, it is inevitable that higher requirements will be imposed on the process of intensity-modulated radiotherapy. Currently, gaps exist in the radiotherapy equipment and personnel qualification among radiotherapy units, and thus the homogenization in the radiotherapy remains to be strengthened in China. With the application of radiotherapy information management system, digital medicine and artificial intelligence technologies in the field of radiotherapy, the original process fails to meet the application needs of the new precise radiotherapy technology. Therefore, this process is designed based on the existing radiotherapy procedures for nasopharyngeal carcinoma in combination with the latest developments in the field of radiotherapy, aiming to establish a novel standard process recommendation, ensuring the standardization and homogenization of radiotherapy and achieve the individualized intensity-modulated radiotherapy for nasopharyngeal carcinoma patients.
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Writing and publishing biomedical research papers in English for academic purposes (EAP) has become an essential requirement for medical postgraduates in China. To face this challenge, medical postgraduates need adapt themselves to the local environment of English as a second language and the transformation from writing for examinations to writing for application. This change determines the features of biomedical research papers, including being application-oriented, using clear and concise language, organizing the discourse by specific genre rules, and assessing the quality according to the completion of communicative purposes. Based on these features, students can exploit the learning strategies of choosing a word suited for the style, structuring a sentence according to the logic, creating a paragraph of continuity and one main idea, and composing the discourse in line with the genre. These strategies may help medical postgraduates effectively improve their ability to write biomedical research papers in English.
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The purpose of tumor staging is to guide treatment, and the treatment for a certain stage should be adjusted based on the changes in disease condition, in order to facilitate better control of tumor. Therefore, the treatment of liver cancer requires follow-up and re-staging to develop better treatment regimens for patients, especially the opportunity for cure. Surgical resection is not suitable for large hepatocellular carcinoma confined to the liver, and after embolization chemotherapy combined with radiotherapy for tumor regression and downstaging, some patients may undergo surgical resection, and the incurable tumor can thus be cured. For liver cancer patients with portal vein tumor thrombus, surgical resection can be performed after tumor thrombus is reduced by neoadjuvant radiotherapy, and the patients undergoing neoadjuvant radiotherapy have a significant increase in survival time than those not undergoing neoadjuvant radiotherapy. Large hepatocellular carcinoma can be downstaged to small hepatocellular carcinoma after multimodality therapy, and then stereotactic radiotherapy or radiofrequency ablation can help to achieve radical treatment. There is an increasing number of clinical reports of radiotherapy for liver cancer downstaging, with a gradual increase in evidence-based level, and thus it holds promise for clinical application.
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With globalization of biomedicine,Chinese postgraduates in medical colleges are facing increasing challenges.Writing and publishing research papers in English have become an essential requirement for their graduation and career development,but for non-native English speakers,having a good command of English for academic purposes (EAP) is of special difficulty.In China,lack of self-written textbooks is a bottleneck that restricts the teaching of EAP.Therefore,guided by EAP theories,this study carries out in-depth demand analysis for graduate students in medical colleges and universities,and designs a textbook framework with genre analysis theory.Based on self-established corpus finally completed an EAP writing textbook for postgraduates of biomedicine.This textbook and the writing and research process can provide implications for construction of EAP textbooks in other principles,thus promoting the all-round development of postgraduate education in China.
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P-glycoprotein(P-gp)is an important efflux protein of ATP-binding cassette transporter superfamily. Cells could be protected from detrimental xenobiotics by the up-regulation of efflux pumps.In this review, an extensive literature search for P-gp induction research was conducted, and a focus was brought onto the P-gp induction models,experiment methods and its applications in drug discovery.We mainly introduced the in vitro cell-based models and in vivo rodent animal models for induction research, methods that investigate induction potency by detecting the protein,gene expression and efflux function,as well as co-regulation between P-gp and other transporters or drug metabolism enzymes.P-gp induction can serve as a clinical therapeutic strategy by reducing the intracellular concentration of deleterious xenobiotics significantly,and the in silico P-gp induction pharmacophore model was also discussed.This review could be of great importance for pre-clinical drug design, the screening of new synthesized compounds and the prediction of potential clinical drug-drug interactions.
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Objective To investigate the different expression of preoperative serum mesothelin level in colon cancer patients.Methods One hundred and twenty five patients who were first diagnosed with colon cancer (a scase group) and 75 healthy subjects (a scontrol group) were enrolled in the Fourth People's Hospital of Yulin from Mar.2014 to Jun.2016.The serum levels of mesothelin both in the preoperative case group and control group were detected by enzyme linked immunosorbent assay.Diagnostic value of mesothelin in colon cancer was evaluated by receiver operating characteristic curve.The survival data of both goups were analyzed by Kaplan-Meier and Logrank test.Results Serum endothelin level in the control group was significantly lower than those in the case group [(0.91 ± 0.80) pg/ml and (7.63 ± 3.25) pg/ml,repectively,t =17.57,P ＜ 0.001].There were significant differences in the serum level of endothelin varied significantly in case group with tumor size,TNM stage,invasion,lymph node metastasis and distal metastasis (P ＜ 0.05).The best preoperative diagnostic value for serum levels of colon cancer was 2.36 pg/ml,and the best preoperative diagnostic value was 8.62 pg/ml for predicting the progression of colon cancer.One hundred and twenty-five cases of colon cancer were divided into low serum mesothelin group (n =56,the level of mesothelin ≤ 8.62 pg/ml) and high serum mesothelin group (n =69,the level of mesothelin ＞ 8.62 pg/ml).The difference of survival between the two groups was statistically significant (t =36.01,P ＜ 0.001).Conclusion Serum mesothelin may serve as a potential biomarker for the diagnosis of colon cancer and its progression.
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Objective To investigate the different expression of preoperative serum mesothelin level in colon cancer patients.Methods One hundred and twenty five patients who were first diagnosed with colon cancer (a scase group) and 75 healthy subjects (a scontrol group) were enrolled in the Fourth People's Hospital of Yulin from Mar.2014 to Jun.2016.The serum levels of mesothelin both in the preoperative case group and control group were detected by enzyme linked immunosorbent assay.Diagnostic value of mesothelin in colon cancer was evaluated by receiver operating characteristic curve.The survival data of both goups were analyzed by Kaplan-Meier and Logrank test.Results Serum endothelin level in the control group was significantly lower than those in the case group [(0.91 ± 0.80) pg/ml and (7.63 ± 3.25) pg/ml,repectively,t =17.57,P ＜ 0.001].There were significant differences in the serum level of endothelin varied significantly in case group with tumor size,TNM stage,invasion,lymph node metastasis and distal metastasis (P ＜ 0.05).The best preoperative diagnostic value for serum levels of colon cancer was 2.36 pg/ml,and the best preoperative diagnostic value was 8.62 pg/ml for predicting the progression of colon cancer.One hundred and twenty-five cases of colon cancer were divided into low serum mesothelin group (n =56,the level of mesothelin ≤ 8.62 pg/ml) and high serum mesothelin group (n =69,the level of mesothelin ＞ 8.62 pg/ml).The difference of survival between the two groups was statistically significant (t =36.01,P ＜ 0.001).Conclusion Serum mesothelin may serve as a potential biomarker for the diagnosis of colon cancer and its progression.
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A qualitative analytical method of liquid chromatography coupled with ion trap time-of-flight mass spectrometry (LC-IT-TOF/MS) was developed for identification of major constituents in propolis from China (Shandong).The LC-IT-TOF-MS was performed on a Shim-pack VP-ODS column (2.0 mm× 150 mm,5 μm) with the mobile phase consisting of acetonitrile and water containing 0.2％ formic acid in gradient mode,and the flow rate was set at 0.3 mL/min.Negative ion mode was used for IT-TOF-MS.According to the accurate molecular weight,MS fragment pathway,comparison with the retention time of reference compounds,total 31 compounds,including twenty-five phenolic acids and six flavonoids were identified.The LC-IT-TOF-MS qualitative analysis method can be used for analyzing major components of propolis quickly and accurately.
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Objective To explore the effect of Yes-associated protein 1 (YAP1) and potential mechanism on erlotinib ( ER) resistance in lung adenocarcinoma.Methods In PC-9 cells and acquired ER resistant PC-9 ( PC-9/ER) cells, the expression changes in YAP1 gene were measured by quantitative real-time PCR( RT-qPCR) and Western blot.Indirect immunofluorescence was adopted to observe the location of YAP1.PC-9/ER cells were treated with the verteporfin ( VP, YAP1 inhibitor) for 24 h and 48 h, respectively.Expression changes in mRNA and proteins of YAP1, AKT and p-AKT were detected in the presence or absence of VP.The effect of VP was analyzed by drug resistance index using Cell Counting Kit 8(CCK-8) assay.Results The resistance index of PC-9/ER cells was (99.80 ±25.81).Compared with PC-9 cells, the expression levels of YAP1 mRNA and protein were increased in PC-9/ER.The inhibitory efficiency of VP was (50.96 ±5.86)%, and the levels of AKT and p-AKT proteins were down-regulated by the inhibition of YAP1 simultaneously.The half maximal inhibitory concentration (IC50) of PC-9/ER decreased from (11.10 ±2.72) to (1.47 ± 0.32)μmol/L (P =0.024).Resistance index was reduced to one eighth of the original.Conclusion These results indicate that the YAP1 mediates ER resistance in lung adenocarcinoma.Suppression of YAP1 can reduce the resistance through PI3K/AKT signaling pathway.Therefore, YAP1 may be a potential target for lung cancer gene therapy.
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@#To investigate the stereoselective pharmacokinetics of itraconazole enantiomers in rats, four cis-ITR stereoisomers at the dose of 15 mg/kg were administered orally to rats. Blood was collected and single stereoisomer of ITZ and hydroxy-itraconazole(OH-ITZ)were determinated simultaneously by LC-MS/MS. Samples were extracted by protein precipitation with acetonitrile. Durashell HILIC column(100 mm×2. 1 mm, 5. 0 m)was used as the analytical column, while a mixture of solvent A(0. 02% acetic acid and 5 mmol/L ammonium acetate in water)and B(50% acetonitrile and 50% methyl alcohol)was used as the mobile phase. A 5. 5 min binary gradient elution(delivered at 0. 5 mL/min)was performed for the separation. LC-MS/MS was performed in positive ion mode with multiple reactions monitoring(MRM). The pharmacokinetic parameters of itraconazole enantiomers after the administration were estimated as follows: the plasma levels and AUC0-∞ of OH-(2S, 4R, 2R)-ITZ and OH-(2S, 4R, 2S)-ITZ were higher than those of OH-(2R, 4S, 2R)-ITZ and OH-(2R, 4S, 2S)-ITZ(P< 0. 001). At the same time, female rats exhibited greater cmax, t1/2, AUC0-∞ than male rats, and the absorption of male rats was more rapid than those of females. The findings indicate significant stereoselective differences in the pharmacokinetic parameters of itraconazole enantiomers and gender difference in rats.
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@#This study aimed at evaluating the antioxidant effects of Guanfu base A(GFA)on acetylcholine(Ach)/CaCl2(CaCl2 10 mg/mL, Ach 66 μg/mL)-induced atrial fibrillation(AF)in rats. SD rats were rando-mized into normal group, model group, GFA treatment groups(6 mg/kg, 12 mg/kg), Amiodarone(Ami)treatment group(50 mg/kg)and Lovastatin(Lov)treatment group(10 mg/kg). The AF durations were measured by electrocardiogram(ECG). The effective refractory periods(AERP)were measured in the left atrial appendage. Oxidative stress-related gene and protein expression was evaluated by RT-PCR and Western blot. The activity of antioxidant enzymes was measured by enzymatic assay. Results indicated that, in comparison with that in the vehicle-treated AF rats, treatment with GFA(6 mg/kg, 12 mg/kg, po), significantly shortened the AF duration and prolonged the AERP in rats. In addition, treatment with GFA reduced the levels of plasma and myocardium malondialdehyde, increased the activity of plasma superoxide dismutase in a dose-dependent manner. Moreover, treatment with GFA mitigated AF-up-regulated p22phox, p47phox, gp91phox, and p67phox NADPH oxidase expression, and AF-increased ratios of membrane to cytosolic Rac-1 in the atrium. It also significantly prevented AF-down-regulated atrial connexin40 expression in rats. Data suggested that GFA(6 mg/kg, 12 mg/kg)has potent anti-oxidant activity and inhibits oxidative-stress-related AF in rats.
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Objective To compare the effect and safety of rituximab plus CHOP (R-CHOP) and CHOP regimens for the treatment of newly diagnosed patients with early-stage primary gastric diffuse large B-cell lymphoma (PG-DLBCL). Methods A total of 65 patients with PG-DLBCL were retrospectively divided into two groups: 35 patients were treated with R-CHOP regimen, the others with CHOP regimen. NHL international efficacy assessment and WHO criteria were used to assess the therapeutic and the adverse reactions respectively. Results The complete remission (CR) rate of R-CHOP group was 74.3 % (26/35), which was significantly higher than that of CHOP group [50.0 % (15/30), P0.05). The Kaplan-Meier survival analysis showed that the five-year survival rates of two groups had no significant difference (88.6%vs 75.0%, P>0.05). The PFS of R-CHOP group was better than that of CHOP group (94.4 months vs 74.9 months, P< 0.05). Conclusion Compared with CHOP regimen , R-CHOP regimen increases the therapeutic efficacy in patients with PG-DLBCL, and dose not increase the adverse reactions.
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As a new interdisciplinary course, the current paper writing course for medical postgraduates exhibits certaln disadvantages. For example, the course does not well target the learners' needs because of the absence of the needs analysis before class;English or biomedical teachers fall to combine English with medicine, thus unable to provide ideal courses. As textbooks are an important means to improve the quality of the course, one way to reform the course is to compile high-quality textbooks by interdisciplinary talents. Meanwhile, the compiling process should be guided by needs analysis as well as the teaching and editing experiences. In addition, the textbooks need to be con-tinuously improved in teaching practice.
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Objective To compare the therapeutic effects of three therapeutics to earlier primary gastric diffuse large B cell lymphoma(PG-DLBCL).Methods By reviewing a data-base of 66 patients with earlier PG-DLBCL from Aug 2000 to Oct 2011 were enrolled,patients were divided into chemotherapy alone(21 cases),radiotherapy combined with chemotherapy(22 cases) and surgery followed chemotherapy group(23 cases),and to comparing the prognosis of the three therapeutics.Results The complete remission rates(CR) of the three groups was 47.6％,77.3％,65.2％ (P ＞ 0.05).The median progression-free survival(PFS)of the three groups in 66 patients was 61.5,90.4 and 79.1 months,the radiotherapy combined group was proven to be significantly better than chemotherapy alone group and surgery followed chemotherapy group(x2 =6.726,P ＜0.05).The 3-year survival rate of the three groups was 81.6％,90.5％ and 82.6％.The five year survival rate was 72.5％,90.5％,82.6％.There was no significant difference (P ＞ 0.05) in 3-year survival rate and 5-year survival rate.Conclusions Radiotherapy combined with chemotherapy can significantly improve the PFS without increasing the risk of other adverse outcomes,and could be the first treatment way for the earlier PG-DLBCL.