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With rapid development of organ transplantation, the issue of global organ shortage has become increasingly prominent. At present, liver transplantation is the most effective treatment for end-stage liver disease. Nevertheless, the shortage of donors has been a key problem restricting the development of liver transplantation. China is a country with a larger number of hepatitis B, and the shortage of donor liver is particularly significant. Many critically ill patients often lose the best opportunity or even die because they cannot obtain a matched donor liver in time. As a strategy to expand the donor pool, ABO-incompatible (ABOi) liver transplantation offers new options for patients who are waiting for matched donors. However, ABOi liver transplantation is highly controversial due to higher risk of complications, such as severe infection, antibody-mediated rejection (AMR), biliary complications, thrombotic microangiopathy, and acute kidney injury, etc. In this article, research progress in preoperative, intraoperative and postoperative strategies of ABOi liver transplantation was reviewed, aiming to provide reference for clinical application and research of ABOi liver transplantation.
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Therapeutic drug monitoring(TDM)has played an important role in clinical medicine for precise dosing.Currently,chromatographic technology and immunoassay detection are widely used in TDM and have met most of the needs of clinical drug therapy.However,some problems still exist in practical appli-cations,such as complicated operation and the influence of endogenous substances.Surface plasmon resonance(SPR)has been applied to detect the concentrations of small molecules,including pesticide residues in crops and antibiotics in milk,which indicates its potential for in vivo drug detection.In this study,a new SPR-based biosensor for detecting chloramphenicol(CAP)in blood samples was developed and validated using methodological verification,including precision,accuracy,matrix effect,and extraction recovery rate,and compared with the classic ultra-performance liquid chromatography-ultraviolet(UPLC-UV)method.The detection range of SPR was 0.1-50 ng/mL and the limit of detec-tion was 0.099±0.023 ng/mL,which was lower than that of UPLC-UV.The intra-day and inter-day ac-curacies of SPR were 98％-114％and 110％-122％,which met the analysis requirement.The results show that the SPR biosensor is identical to UPLC-UV in the detection of CAP in rat blood samples;moreover,the SPR biosensor has better sensitivity.Therefore,the present study shows that SPR technology can be used for the detection of small molecules in the blood samples and has the potential to become a method for therapeutic drug monitoring.
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Astragali Radix(AR)is a clinically used herbal medicine with multiple immunomodulatory activities that can strengthen the activity and cytotoxicity of natural killer(NK)cells.However,owing to the complexity of its composition,the specific active ingredients in AR that act on NK cells are not clear yet.Cell membrane chromatography(CMC)is mainly used to screen the active ingredients in a complex system of herbal medicines.In this study,a new comprehensive two-dimensional(2D)NK-92MI CMC/C18 column/time-of-flight mass spectrometry(TOFMS)system was established to screen for potential NK cell acti-vators.To obtain a higher column efficiency,3-mercaptopropyltrimethoxysilane-modified silica was synthesized to prepare the NK-92MI CMC column.In total,nine components in AR were screened from this system,which could be washed out from the NK-92MI/CMC column after 10 min,and they showed good affinity for NK-92MI/CMC column.Two representative active compounds of AR,isoastragaloside Ⅰ and astragaloside Ⅳ,promoted the killing effect of NK cells on K562 cells in a dose-dependent manner.It can thus suggest that isoastragaloside Ⅰ and astragaloside Ⅳ are the main immunomodulatory compo-nents of AR.This comprehensive 2D NK-92MI CMC analytical system is a practical method for screening immune cell activators from other herbal medicines with immunomodulatory effects.
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P-glycoprotein (P-gp) highly expressed in cancer cells can lead to multidrug resistance (MDR) and the combination of anti-cancer drugs with P-gp inhibitor has been a promising strategy to reverse MDR in cancer treatment. In this study, we established a label-free and detergent-free system combining surface plasmon resonance (SPR) biosensor with styrene maleic acid (SMA) polymer membrane proteins (MPs) stabilization technology to screen potential P-gp inhibitors. First, P-gp was extracted from MCF-7/ADR cells using SMA polymer to form SMA liposomes (SMALPs). Following that, SMALPs were immobilized on an SPR biosensor chip to establish a P-gp inhibitor screening system, and the affinity between P-gp and small molecule ligand was determined. The methodological investigation proved that the screening system had good specificity and stability. Nine P-gp ligands were screened out from 50 natural products, and their affinity constants with P-gp were also determined. The in vitro cell verification experiments demonstrated that tetrandrine, fangchinoline, praeruptorin B, neobaicalein, and icariin could significantly increase the sensitivity of MCF-7/ADR cells to Adriamycin (Adr). Moreover, tetrandrine, praeruptorin B, and neobaicalein could reverse MDR in MCF-7/ADR cells by inhibiting the function of P-gp. This is the first time that SMALPs-based stabilization strategy was applied to SPR analysis system. SMA polymer can retain P-gp in the environment of natural lipid bilayer and thus maintain the correct conformation and physiological functions of P-gp. The developed system can quickly and accurately screen small molecule ligands of complex MPs and obtain affinity between complex MPs and small molecule ligands without protein purification.
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Objective To evaluate therapeutic effects of dihydrotanshinone Ⅰ on hepatic fibrosis based on liver metabolomics method. Methods 28 rats were randomly divided into four groups including control group, hepatic fibrosis model group and dihydrotanshinone Ⅰ low dose group and dihydrotanshinone Ⅰ high dose group. The dihydrotanshinone Ⅰ treated groups received dihydrotanshinone Ⅰ for 28 days. The rat liver samples were collected and analyzed by liquid chromatography-mass spectrometer (LC-MS). The OPLS-DA pattern recognition analysis of metabolomics differences among the groups and therapeutic effects of dihydrotanshinone Ⅰ on hepatic fibrosis were evaluated. Results 38 metabolites were identified through liver metabolomics analysis. The possible mechanism of hepatic fibrosis was mainly involved glutathione metabolism, melatonin metabolism, amino acid metabolism, lipid metabolism and TCA cycle. The hepatic fibrosis induced by TAA was reversed by dihydrotanshinone Ⅰ. Conclusion Dihydrotanshinone Ⅰ provided satisfactory therapeutical effects on hepatic fibrosis through partially regulating the perturbed glutathione metabolism, melatonin metabolism, amino acid metabolism, lipid metabolism, TCA cycle.
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De novo malignancy after liver transplantation is an important factor that affecting the long-term survival of recipient. The main risk factors for de novo malignancy include immunosuppression and many factors of recipients, such as age, gender, race, primary disease, preoperative tumor history and precancerous lesion, carcinogenic virus infection, smoking and drinking, etc. Currently, there is no standardized monitoring scheme after liver transplantation, but planned monitoring is required for high-risk recipients, thus to achieve early diagnosis and improve the survival rate. This article summarized the incidence, prognosis and related risk factors of de novo malignancy after liver transplantation, which provided reference for improving long-term survival rate of recipients after liver transplantation.
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Objective To identify the blood components of Fuzheng Huayu capsule by ultra performance liquid chromatography-high resolution time-of-flight mass spectrometry (UHPLC-Q-TOF/MS). Methods ACQUITY UPLCHSS T3 (2.1 mm × 100 mm, 1.8 μm) was used to chromatographic separation; mobile phase was 0.1% formic acid aqueous solution (A) −0.1% formic acid acetonitrile solution (B). The gradient elution conditions included: 0−3 min, 2% B; 3−18 min, 2%−50% B; 18−22 min, 50%−95% B; 22−25 min, 95% B. The equilibration time was 10 min, the flow rate was 0.40 ml/min, and the analysis time was 25 min. The mass spectrometry was characterized by electrospray ionization by a positive-negative ion mode scan with a range of 100-1 100 m/z. Results 49 components were identified in the serum samples at one time, of which 4 were positive and negative ion modes. Conclusion The blood components of Fuzheng Huayu capsule were clarified by this method, which enriched the scientific connotation of Fuzheng Huayu capsule, and laid the foundation for the in-depth study of the compound.
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A multi-label based level set model for multiple sclerosis lesion segmentation is proposed based on the shape, position and other information of lesions from magnetic resonance image. First, fuzzy c-means model is applied to extract the initial lesion region. Second, an intensity prior information term and a label fusion term are constructed using intensity information of the initial lesion region, the above two terms are integrated into a region-based level set model. The final lesion segmentation is achieved by evolving the level set contour. The experimental results show that the proposed method can accurately and robustly extract brain lesions from magnetic resonance images. The proposed method helps to reduce the work of radiologists significantly, which is useful in clinical application.
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Humans , Algorithms , Magnetic Resonance Imaging , Multiple Sclerosis , Diagnostic ImagingABSTRACT
Objective To optimize a method for extracting traditional Chinese medicine composition with insomnia,and to prepare the insomnia granules for quality control.Methods The optimal extraction process was screened by orthogonal test using high-performance liquid chromatography with geniposide as the evaluation index.The particle size,bulk density,angle of repose,moisture,solubility,hygroscopicity and loading difference of the insomnia granule were evaluated,and the difference between the trial test and the pilot test were analyzed to comprehensively monitor the quality of the insomnia granule.Results The best extraction process was to add 10 times of water and cooked it three times for 1.5 hours each time.The average yield rate of dry extract of the pilot test and trial test was 22.10％,15.52％,and the average yield of powder was 84.96％ and 93.12％,respectively.The conversion rate from the pilot test to the trial test is 76.97％.Both the trial test and the pilot test particles met the quality requirements of the 2015 edition of the pharmacopoeia.Conclusions The preparation method of the insomnia granules is simple and the quality is uniform.The results of the pilot scale showed that the conversion rate is high,the quality is controllable,and the technical feasibility of industrial production is obtained.
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Network pharmacology is the basis of system biology,systematically expounded the interaction of the princi-ple and regulation between body and the drug,representing the idea of the modern biomedical philosophy and researching mod-el.It could be more easily understand the mechanism of action of Traditional Chinese Medicine treatment of diseases by the net-work pharmacology-related technical means.Network pharmacology is widely used in Traditional Chinese Medicine research in the current.The application and development of network pharmacology in the field of Traditional Chinese Medicine research in recent years were introduced in this paper from the aspects of Traditional Chinese Medicine concept,network pharmacology and network pharmacology application.
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Surface plasmon resonance(SPR) is an optical phenomenon arises from mass changes on sensors based on in-teraction between substances ,which could monitor the interaction between biomolecules quickly and accurately .It has the ad-vantage of label-free ,high specificity ,high accuracy ,real-time and on-line monitoring ,which has attracted comprehensive at-tention in recent years .SPR biosensors could be applied in drug discovery ,clinical diagnosis ,food safety ,environment monito-ring and proteomics .In this manuscript ,the application of SPR biosensors in food safety ,environment monitor and biomedical analysis have been reviewed ,which could provide reference to related research .
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In recent years ,pharmacokinetics of traditional Chinese medicine has become essential for the modernization of traditional Chinese medicine .Pharmacokinetics is an important means for connecting traditional Chinese medicine with west-ern medicine .Medications exert efficacy only when there is sufficient concentration at the target sites .The drug concentration is not only related to the dosage ,but is also closely correlated to the metabolic processes in human body .Most pharmacokinetic studies of traditional Chinese medicine are based on healthy animals ,which ignore significant changes of pharmacokinetic pa-rameters in the diseased state .In this paper ,the comparative pharmacokinetics of the traditional Chinese medicine based on ani-mal models in their diseased states was reviewed .Developmental trends of pharmacokinetics of traditional Chinese medicine with different animal models were also discussed .
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According to the Chinese Pharmacopoeia 2015, only processed Aconitum tubers can be clinically applied, and the effect of processing is unclear. This research aimed to explore the effect of processing on cardiac efficacy of alkaloids in Aconitum tubers. First, the chemical ingredients in unprocessed and processed Aconitum tubers were identified and compared by using high performance liquid chromatography time-of-flight mass spectrometry (HPLC-TOF/MS) and multivariate pattern recognition methods. Then the representative alkaloids in Aconitum tubers, aconitine, benzoylaconine, and aconine, which belong to diester-diterpenoid alkaloids, monoester-diterpenoid alkaloids, and amine-diterpenoid alkaloids, respectively, were selected for further validation of attenuated mechanism. Subsequent pharmacological experiments with aconitine, benzoylaconine, and aconine in SD rats were used to validate the effect of processing on cardiac functions. After processing the Aconitum tubers, it was found that the contents of diester-diterpenoid alkaloids were reduced, and those of monoester-diterpenoid alkaloids and amine-diterpenoid alkaloids were increased, suggesting that diesterditerpenoid alkaloids were transformed into monoester-diterpenoid alkaloids and amine-diterpenoid alkaloids. Through further decocting the aconitine in boiling water, it was confirmed that the three alkaloids could be progressively transformed. Pharmacological experiments with aconitine, benzoylaconine, and aconine in SD rats showed that aconitine at a dose of 0.01 mg/kg and aconine at a dose of 10 mg/kg enhanced the cardiac function, while benzoylaconine at a dose of 2 mg/kg weakened the cardiac function. The effect of processing is attributed to the transformation of the most toxic diester-diterpenoid alkaloids into less toxic monoesterditerpenoid alkaloids and amine-diterpenoid alkaloids.
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The paper described the role of big data for health economy development and the present data mining and integration of health economy management.It pointed out the importance of overall data criteria management,IT system integration management,healthcare data collection,and normalization of data mining and integration process.The authors also recommended new concepts,technology reserve and institutional development,to provide powerful technical support for the macro decision making,budget allocation,performance analysis,and performance appraisal of the health economy.
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Objective To explore specific variables related to cisplatin induced acute kidney injury ,serum metabonomics techniques were applied and simultaneously the value of intervention effects of L-carnitine were appraised .Methods 19 mice were divided into the normal control group ,model group ,and intervention group ,After a three day accommodation period ,the intervention group was given L-carnitine (400 mg/kg ,ip) .Two days later ,cisplatin (20 mg/kg ,ip) was given to the model and intervention groups .The body weight of every mouse in each group was measured daily .Two days after the serum sample of each mice was collected and analyzed by LC-MS ,pattern recognition analysis of metabolomics differences among the groups , and the effectiveness of L-carnitine intervention were evaluated .Results A total of 28 metabolites were identified through ser-um metabolomics analysis .Our data shows that there is a possible mechanism that cisplatin induced AKI was mainly involved in changing phospholipids ,amino acid and fatty acid metabolic pathways and L-carnitine mitigates the damage of acute kidney in-jury induced by cisplatin .Conclusion L-carnitinecan alleviates cisplatin induced acute kidney injury by regulating tryptophan metabolism ,glutamate metabolism ,and energy metabolism .
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Objective To analyze the different metabolites of the classical activated (M1) ,alternatively activated (M2) and resting BV2 cells by metabolomics method .Methods The mRNAs of several potential biomarkers were determined by real-time PCR analyses to confirm the state of BV2 cells .Static GC-MS combined with metabolomics technology was used to analyze the metabolic changes .Results There were 15 biomarkers identified between the M1 group and the resting group ,and 15 biomarkers were found in the M2 group and the resting group .Conclusion The present study provides an effective way to reveal the mechanism of the polarization of BV 2 cell ,and it might provide a theoretical basis to prevent or treat the neurodegen-erative diseases .
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Objective To investigate the metabolism in miconazole-treated Candida albicans ,search for possible biomar-kers and discuss the mechanism of miconazole .Methods GC-MS was employed to determine the metabolic fingerprint of Can-dida albicans before and after treatment with miconazole ,and the difference based on multivariate was compared by statistical analysis ,the potential biomarkers were screened out and the mechanism of miconazole was discussed .Results Twenty three metabolites was screened out as potential biomarkers ,and they were primarily involved in amino acid metabolism ,citrate cycle , glycolysis and lipid metabolism .Conclusion The antifungal activity of miconazole was played by affecting a variety of metabolic pathways .
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Objective To study the clinical features and prognostic risk factors of patients with autoimmune hepatitis-related hepatocellular carcinoma (AIH-HCC).Methods We reviewed the clinical data of 40 patients with AIH-HCC who were treated at the 302 Hospital between May 1,2008 and April 30,2013,and analyzed the clinical characteristics and prognostic risk factors of these patients.Results These patients were diagnosed to have HCC at a mean ± SD of 55.1 ± 13.5 years (range 28-76 years).The median duration from the time of confirmed cirrhosis to a diagnosis of HCC was 49.2 ± 44.5 months (range 3-194 months).The median survival of the AIH-HCC patients was 16.0 ±4.0 months (range 1-44 months),and the 1-year survival rate was 54.0％.Univariate analysis showed AFP,tumor size,tumor number were related to prognosis (P ＜ 0.05) ; while gender,age,IAIHG score,category,history of blood transfusion,alcohol-drinking and smoking did not significantly affect the patients' survival (P ＞ 0.05).Multivariate regression analysis showed AFP and tumor number were independent prognostic factors.Most of these patients received transcatheter arterial chemoembolization(TACE),however the survival rate of those patients who received hepatectomy was significantly higher than those who received TACE or accepted conservative treatment.Conclusion Liver cirrhosis in AIH is the sine qua non for HCC development,which subsequently occurs at a rate of 1.65％ per year.Patients who had AFP-negativity or a single tumor had a better prognosis.Surgical treatment prolonged survival.
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DraIII is a type IIP restriction endonucleases (REases) that recognizes and creates a double strand break within the gapped palindromic sequence CAC↑NNN↓GTG of double-stranded DNA (↑ indicates nicking on the bottom strand; ↓ indicates nicking on the top strand). However, wild type DraIII shows significant star activity. In this study, it was found that the prominent star site is CAT↑GTT↓GTG, consisting of a star 5' half (CAT) and a canonical 3' half (GTG). DraIII nicks the 3' canonical half site at a faster rate than the 5' star half site, in contrast to the similar rate with the canonical full site. The crystal structure of the DraIII protein was solved. It indicated, as supported by mutagenesis, that DraIII possesses a ββα-metal HNH active site. The structure revealed extensive intra-molecular interactions between the N-terminal domain and the C-terminal domain containing the HNH active site. Disruptions of these interactions through site-directed mutagenesis drastically increased cleavage fidelity. The understanding of fidelity mechanisms will enable generation of high fidelity REases.
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Amino Acid Sequence , Base Sequence , Calorimetry, Differential Scanning , Catalytic Domain , Crystallography, X-Ray , DNA , Metabolism , DNA Cleavage , Deoxyribonucleases, Type II Site-Specific , Chemistry , Genetics , Metabolism , Escherichia coli , Metabolism , Molecular Sequence Data , Mutagenesis, Site-Directed , Recombinant Proteins , Chemistry , Genetics , Metabolism , Sequence Alignment , Substrate SpecificityABSTRACT
<p><b>OBJECTIVE</b>To investigate the role of apoptosis stimulating protein 2 of p53 (ASPP2) phosphorylation status in the regulation of ASPP2-p53 apoptotic pathway activity.</p><p><b>METHODS</b>Cells were individually transfected with green fluorescent protein (GFP)-encoding vector, constitutively non-phosphorylatable ASPP2 mutant-ASPP2 (Am)-encoding vector, and wild type ASPP2 (Aw)-encoding vector) plasmids, respectively, to make them overexpressing phosphorylated and non-phosphorylated ASPP2 proteins, respectively. Cell apoptosis was induced by oxaliplatin. The apoptosis rate of cells was determined by flow cytometry after staining with FITC-conjugated annexin V and PI. ASPP2 protein level and its phosphorylation status were observed by Western blot. The interaction between ASPP2 and p53 was observed by immunoprecipitation assay.</p><p><b>RESULTS</b>Oxaliplatin induced cell apoptosis and caused phosphorylation of ASPP2 at ser92/ser361 in the HCT116 cells. The apoptosis rate of Aw and Am plasmids-transfected cells were (3.8 ± 1.0)% and (3.9 ± 1.2)% respectively, statistically with a non-significant difference (P > 0.05) in comparison with that of the GFP plasmid-transfected cells [(4.0 ± 0.8)%]. After oxaliplatin treatment, the apoptosis rate of Aw plasmid-transfected cells was (46.7 ± 3.9)%, significantly higher than that of the Am and GFP plasmid-transfected cells [(40.1 ± 10.2)% and (37.1 ± 6.9)%, respectively, P < 0.05], however, there was no statistically significant difference (P > 0.05) between Am and GFP plasmid-transfected cells. These results indicate that phosphorylated ASPP2 promoted the oxaliplatin-induced apoptosis of HCT116 cells through a p53-dependent pathway. Phosphorylation status of ASPP2 influenced its binding activity to p53.</p><p><b>CONCLUSION</b>Phosphorylation status of ASPP2 modulates p53 apoptotic function in oxaliplatin-induced apoptosis of colorectal cancer HCT116 cells.</p>