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OBJECTIVE To investigate the effects of Compound troxerutin and poreine cerebroside injection on the activity of cytochrome P450 （CYP450） enzyme in vivo and in vitro. METHODS Human liver microsomes were incubated with Compound troxerutin and poreine cerebroside injection （volume fraction 0.05%-10%） and the specific probe substrates of CYP1A2， CYP2B6， CYP2C8， CYP2C9， CYP2C19， CYP2D6 and CYP3A4 for 30 min. The production of corresponding metabolites was detected by ultra-high performance liquid chromatography-tandem mass spectrometry （UPLC-MS/MS）， and the half inhibitory concentration （IC50） was calculated. The relative mRNA expression （i.e. induction multiple） of CYP450 enzyme was determined by real-time fluorescence quantitative PCR after human primary hepatocytes were incubated with Compound troxerutin and poreine cerebroside injection （volume fraction 0.05%-10%） or 3 positive inducers of CYP1A2， CYP2B6， CYP3A4 for 48 hours. Male SD rats were randomly divided into control group （normal saline+probe substrates of CYP1A2， CYP2B6， CYP2C8， CYP2C9， CYP2C19， CYP2D6， CYP3A4 8， 2， 1， 1， 10， 10， 8 mg/kg） and experimental group （Compound troxerutin and poreine cerebroside injection 0.9 mL/kg+probe substrates of CYP1A2， CYP2B6， CYP2C8， CYP2C9， CYP2C19， CYP2D6， CYP3A4 8， 2， 1， 1， 10，10， 8 mg/kg）， with 6 rats in each group. The pharmacokinetic parameters of probe substrates were detected by UPLC-MS/MS and Cocktail probe drug method. RESULTS After the lzqpharm@126.com treatment of 0.05%-10% Compound troxerutin and poreine cerebroside injection， the activities of CYP2B6， CYP2C8 and CYP2C19 in human liver microsomes had no significant change， and IC50 could not be fitted； IC50 of CYP1A2， CYP2C9， CYP2D6 and CYP3A4 were 419.90%， 97.78%， 176.00%， 19.42%， respectively. After the treatment of 0.05%-10% Compound troxerutin and poreine cerebroside injection， the average induction multiple of CYP3A4 mRNA in human primary hepatocytes （No. MHK） was 4.88 （and the average induction multiples of 2 concentration points were higher than 2）. After the treatment of Compound troxerutin and poreine cerebroside injection， AUC0－t and AUC0－∞ of CYP2C8， CYP2C9 and CYP2C19 substrates were increased significantly， CL of CYP2C8 and CYP2C19 substrates were decreased significantly， while t1/2 of CYP2C9 substrate was prolonged significantly （P＜0.05）. CONCLUSIONS Compound troxerutin and poreine cerebroside injection has no obvious inhibitory effect on CYP1A2， CYP2B6， CYP2C8， CYP2C9， CYP2C19， CYP2D6 and CYP3A4 in human liver microsomes in vitro， but can induce the mRNA expression of CYP3A4 in human primary hepatocytes in vitro， and can inhibit the activities of CYP2C8， CYP2C9 and CYP2C19 in rats in vivo.
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Enzyme-catalyzed CO2 reduction to value-added commodities is important for alleviating the global environmental issues and energy crises due to high selectivity and mild conditions. Owing to high energy density, formic acid or methanol produced from CO2 using formate dehydrogenase (FDH) or multi-enzyme cascades are promising target chemicals for CO2 utilization. However, the low activity, poor stability and low reusability of key enzymes involved in such process hampered its large-scale application. Enzyme immobilization provides an effective solution to these problems and significant progress have been made in immobilization carriers. Moreover, integration of enzyme immobilization with other catalysis techniques have been explored extensively. This review summarized the recent advances in the immobilization of enzymes using membranes, inorganic materials, metal-organic frameworks, covalent organic frameworks and other carriers, and illustrated the characteristics and advantages of different immobilization materials and immobilization methods. The synergistic effects and applications of immobilized enzymes and electrocatalytic or photocatalytic coupling reaction systems for CO2 reduction were further summarized. Finally, the current challenges of enzyme immobilization technology and coupling reaction systems were pointed out and their development prospects were presented.
Subject(s)
Enzymes, Immobilized , Carbon Dioxide , Catalysis , Formate Dehydrogenases , Metal-Organic FrameworksABSTRACT
The report elaborated a case of a 52-year-old female patients with over 10 years of schizophrenia complicating 12 months of stupor. After a course of modified electroconvulsive therapy（MECT） combined with risperidone oral solution， the patient gradually became active and functionally recovered， and remained stable. This case suggests that MECT combined with risperidone may allow schizophrenia patients in a state of prolonged stupor to obtain clinical rehabilitation and effectively stabilize psychotic symptoms. The discussion is based on this case with a view to providing references for clinical treatment.
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The role of malate dehydrogenase 2 (MDH2) in tumors is double-sided,it has a cancerpromoting effect in some tumors and an inhibitory effect in other tumors.The function of MDH2 is related to energy metabolism,tumor resistance and its pseudo hypoxia.MDH2 plays an important role in the occurrence,development,invasion and metastasis of tumors.An in-depth understanding of the functional mechanism of MDH2 in tumors can provide new molecular targets for tumor intervention in the clinic.
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The safety of TCM injection triggered attentions and hotspots in recent years in China.The centralized monitoring of TCM injection provided important evidence for analyzing the safety risk of TCM injections,recognizing adverse reactions and contraindications and perfecting the instructions.This study aimed at exploring the ethical problems on centralized monitoring.In this paper,we retrieved and screened the ethical issues of TCM injections over hospital centralized monitoring in China National Knowledge Infrastructure (CNKI,1979-Ju1.,2016).Issues over it were put forward and addressed.It is found that the current ethical issues related to hospital centralized monitoring lacks sufficient attentions,corresponding norms and requirements.Based on the ethical issues reflected from the literatures,suggestions should be pressed ahead with the ethical review of centralized surveillance,signing of informed consents,registration of research programs,data statistics and reporting stages,for the better protection of the rights and interests of subjects and improvement of research quality.
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OBJECTIVE:To investigate the regularity and characteristics of adverse drug reactions (ADR) induced by Xianling gubao capsule,and to provide reference for rational drug use in the clinic.METHODS:ADR induced by Xianling gubao capsule were retrieved from CJFD,CBM,Wanfang database,VIP during Jan.2007-Oct.2016.The related information of 185 ADR cases were statistically analyzed.RESULTS:Among 185 patients,primary disease was mainly osteoporosis (63 cases,34.05％).The incidence of ADR induced by drug combination (70.81％) was higher than single drug (29.19％).ADR mostly occurred within 90 d after medication (67.03％).Main clinical manifestation was digestive system damage (82.68％).Most patients (61.62％) did not need treatment,symptomatic treatment or drug withdrawal to relieve ADR symptoms.CONCLUSIONS:The monitoring for ADR induced by Xianling gubao capsule should be strengthened in clinic,especially for ADR of liver fuction,soas to promote rational drug use.
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OBJECTIVE:To investigate the regularity and characteristics of adverse drug reactions (ADR) induced by Xianling gubao capsule,and to provide reference for rational drug use in the clinic.METHODS:ADR induced by Xianling gubao capsule were retrieved from CJFD,CBM,Wanfang database,VIP during Jan.2007-Oct.2016.The related information of 185 ADR cases were statistically analyzed.RESULTS:Among 185 patients,primary disease was mainly osteoporosis (63 cases,34.05％).The incidence of ADR induced by drug combination (70.81％) was higher than single drug (29.19％).ADR mostly occurred within 90 d after medication (67.03％).Main clinical manifestation was digestive system damage (82.68％).Most patients (61.62％) did not need treatment,symptomatic treatment or drug withdrawal to relieve ADR symptoms.CONCLUSIONS:The monitoring for ADR induced by Xianling gubao capsule should be strengthened in clinic,especially for ADR of liver fuction,soas to promote rational drug use.
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At present,the various levels of safety evaluations of traditional Chinese medical (TCM) injections were in force in post-marketing clinical researches,while the process quality is guaranteed with difficulty.Therefore,it is requisite to call for technical guidance.By drawing lessons from the international experience of drug marketing safety evaluation and the related methods,we proposed the key techniques of quality control for clinical safety evaluation of TCM injections from the three aspects:preparation,implementation and summarization of researches,combining with the characteristics of TCM injections.The key techniques contained some scientific problems,ethics,publicity,data management,statistical analysis,specification report,etc.This paper comprehensively introduced the requisite technologies and methods over research quality,laying a foundation for the studies of post-marketing clinical safety evaluation of TCM injections.
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Purpose To study the expression of Ech1 in hepatocarcinoma and its clinical significance, and to explore the relationship between subcellular location of Ech1 and malignant biologic behaviour of hepatocarcinoma. Methods Immunohistochemical analysis was used to detect Ech1 expression in the 20 cases of normal liver tissue and the 30 cases of hepatocarcinoma. Subcellular location of Ech1 in Hca-F and FEch1-down cell was observed with subcellular protein extraction. Results The expression of Ech1 in primary hepa-tocarcinoma was increased compared to that of normal liver tissues ( P0. 05). Ech1 was found expressed almost at the same location although the expression level one is normal and the other is downregulation. Ech1 expres-sion was found in cytosol, membrane fraction, and its expression was higher in cytosol than other fractions both in Hca-F cell and Ech1 downregulated Hca-F cell. Conclusions The expression of Ech1 in primary hepatocarcinoma was increased, which may indicate that Ech1 is a critical factor in the development of primary hepatocarcinoma, but the subcellular location of Ech1 has not much contribution to that.
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This study was aimed to compare the function of dendritic cells (DCs) in patients of Y in-Huang syn-drome and Y ang-Huang syndrome from the peripheral blood of HBV related hepatic failure. Jaundice patients of HBV related hepatic failure were divided into two groups, which were the Y ang-Huang syndrome group and Y in-Huang syndrome group. And a healthy control group was also established. The DCs were separated and cultured in vitro from PBMCs in the peripheral blood. Surface molecules such as HLA-DR, CD80, CD86, CD83 and CD1αwere detected by the flow cytometry. And the level of IFN- α and IL-4 in the supernatant of DCs were also de-tected. The expression difference of inflammatory cytokines and immune cells between Y in-Huang and Y ang-Huang syndrome in patients of HBV related hepatic failure were compared. The results showed that compared with healthy people, the expression rate of DCs phenotype such as HLA-DR, CD1α, CD83, CD80, CD86 in patients of HBV related hepatic failure was significantly decreased (P < 0.01); the excreted factor IFN-α had a significant rising (P < 0.01). Compared to Y ang-Huang syndrome group, the expression rate of CD83 and CD86 in the Y in-Huang syndrome group of HBV related hepatic failure patients was significantly reduced (P < 0.01). And the ex-creted factor of IL-4 had a significant rising in Y in-Huang syndrome group (P < 0.01). Compared to the Y in-Huang syndrome group, the excreted factor IFN-α in the Yang-Huang syndrome group had a significant rising (P< 0.01). It was concluded that DCs function of patients with HBV related hepatic failure in both Y in-Huang syn-drome and Y ang-Huang syndrome group showed low immune function. And the immune function of the Y in-Huang syndrome group was lower. There was excessive releasing of inflammatory factors in the Y ang-Huang syn-drome group. And there was enhanced anti-inflammatory cytokine expression in the Y in-Huang group.
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Objective Study on the clinic value of the application of two-dimensional and three-dimensional sonography on observing the fetal facial structure. Methods Applying Voluson 730 three-dimensional probe surface imaging mode and two-dimensional probe to make sonography on 16～48 weeks fetus in 1805 cases, emphasized on observing the fetal facial structure, saving the image information, making three-dimensional reconstruction and comparing the result of post partum and the result after induction of labor. Results In 1805 cases, applying two-dimensional and three-dimensional sonography to observe the facial structure of the fetus of 23～35 weeks, the display rate is 93.1% and 95.1% respectively, and there is no obvious difference between the two modes. The three-dimensional is higher than two-dimensional for the fetus less than 23 weeks, with the display rate 69.6% and 84.8% respectively, and the two-dimensional is a bit higher than three-dimensional for the fetus more than 35 weeks, with the display rate 90.4% and 88.7% respectively. One cleft lip case is excluded. Conclusion As long as mastering the optimum examination time and operation skill, there is no obvious difference between the display rate of two-dimensional and three-dimensional sonography on observing the fetal facial structure, the two modes can be complementary in the work to improve the accuracy of the diagnosis and be favorable for the prepotency.
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This paper introduces the international experiments of risk management in clinical trails, responsibility of sponsor, responsibility of investigator and responsibility of other participators and to help to improve our management level of clinical trails.