Inhibitory effect of resveratrol on the pharmacokinetic of ibrutinib by UPLC-MS/MS.

OBJECTIVE: To investigate the impact of resveratrol on the metabolism of ibrutinib in vitro and in vivo. METHODS: In vitro, rat liver microsomes (RLM) and human liver microsomes (HLM) were used to study. In vivo, 18 male SD rats were randomly divided into three groups (n = 6): ibrutinib and the multiple dose of 100 mg/kg resveratrol for consecutive 7 days (Group A), ibrutinib and the single dose of 100 mg/kg resveratrol (Group B), ibrutinib (Group C). Processed samples were analyzed by UPLC-MS/MS. RESULTS: Resveratrol showed inhibition on RLM and HLM in vitro. The IC50 of resveratrol was 8.745 µM in RLM and 7.789 µM in HLM. Furthermore, Groups A and B both increased the AUC and reduced the CLz/F. The Cmax of Group A and the MRT(0-t) of Group B were significantly improved. CONCLUSIONS: Resveratrol inhibits the pharmacokinetic of ibrutinib in vitro and in vivo. It is necessary to pay more attention to adjust the dose of the drug when resveratrol is used in combination with ibrutinib.

Effects of ketoconazole, voriconazole, and itraconazole on the pharmacokinetics of apatinib in rats.

We investigated the effect of azole antifungal drugs (ketoconazole, voriconazole, and itraconazole) on the pharmacokinetics of apatinib in rats. The rats in ketoconazole, voriconazole, and itraconazole groups received single-dose apatinib 30 mg/kg after the oral administration of ketoconazole, voriconazole, and itraconazole, respectively. Co-administration of ketoconazole or voriconazole significantly increased the apatinib Cmax and AUC(0-t) and decreased the clearance. Co-administration of itraconazole did not significantly affect the pharmacokinetics parameters of apatinib. It could be concluded that both ketoconazole and voriconazole significantly increase the exposure of apatinib, and affect the pharmacokinetics of apatinib in rat. Apatinib can be co-administered with itraconazole, but ketoconazole and voriconazole should be avoided if possible or be underwent therapeutic drug monitoring of apatinib. A further clinical study should be conducted to investigate the inhibitory effect of azole antifungal drugs on the apatinib plasma concentration.

Enhanced red emission from BaMoO4 : Eu3+ by Bi3+ co-doping.

A series of Bi3+ ,Eu3+ -doped BaMoO4 phosphors was synthesized using a hydrothermal method. The crystal structure, morphology and optical properties of the phosphors were studied using X-ray diffraction (XRD), scanning electron microscope (SEM) and photoluminescence (PL) measurements. Three different particle morphologies were detected in the SEM observation. The energy dispersive spectroscopy (EDS) results indicated that the solubility of Bi3+ in spherical or rugby-like BaMoO4 particles was very low and the excess Bi3+ element was cumulated in the irregular particles. Characteristic emissions of Eu3+ ions (5 D0  â†’ 7 FJ ; J = 0, 1, 2, 3, 4) were observed under excitation in ultraviolet (UV) light, with the most intense transition being the 5 D0  â†’ 7 F2 transition. Energy transfer from MoO42- and Bi3+ to Eu3+ can be readily achieved. Red emission intensity of Eu3+ was enhanced by a factor of two by co-doping with a small amount of Bi3+ . Optical properties as a function of Bi3+ content were studied and the optimum Bi3+ content in BaMoO4 nanocrystals was determined to be 0.4 mol%.

Function of 38 variants CYP2C9 polymorphism on ketamine metabolism in vitro.

BACKGROUND: Cytochrome P450 proteins (CYP 450) is the most important enzyme system of drug phase I metabolism in liver. In previous reports, reduced efficiency or increased risk of adverse events can be affected by primary sequence mutation in CYP450. AIM: To investigate the effect of gene polymorphism on the metabolism of ketamine in vitro, including the new alleles: 2C9*58, *59 and *60. METHOD: Incubation system which was contained insect microsome, b5, NADPH and 1M PBS incubated 10 µM-1000 µM ketamine in 37 °C for 40 min concentration of norketamine was analyzed by ultra-performance liquid chromatography-tandem mass spectrometry system (UPLC-MS/MS). RESULT: Catalytic activity of thirty-eight CYP2C9 alleles on ketamine metabolism to norketamine was surveyed. Compared with 2C9*1, three alleles (2C9*40, *49 and *51) was demonstrated dramatically increased intrinsic clearance (1.2-fold-3.75-fold); four subtypes (2C9*27, *31, *41 and *56) exhibited no significantly change on enzyme activity. The resting 31 alleles expressed different degrees of reduction compared with wild type. CONCLUSION: The result of research warns that attention should be more paid on individual who carry on the special 2C9 alleles under the situation of administrating ketamine.

3D Reconstruction Aids Surgery For Complicated Hepatolithiasis.

BACKGROUND/AIMS: Three-dimensional (3D) imaging may improve surgical interventions for complicated hepatolithiasis. METHODOLOGY: Between July 2008 and December 2012 a total of 131 patients with complicated hepatolithiasis underwent surgical therapy in the Department of Hepatobiliary Surgery Zhujiang Hospital, Southern Medical University. 77 patients received preoperative planning using a computed tomography (CT)-based 3D reconstruction technique, and 54 received treatment based on preoperative planning with traditional imaging (CT, ultrasonography, magnetic resonance imaging/magnetic resonance cholangiography). Perioperative and long-term outcomes were analyzed. RESULTS: 3D reconstruction facilitated significantly more accurate diagnosis of pathological morphology than conventional imaging methods, as confirmed during surgery. Patients that received 3D reconstruction preoperative planning had significantly better clinical outcomes. The immediate stone clearance rates were 92.2% and 61.1%, respectively. Additional postoperative choledochoscopic lithotripsy raised the clearance rates to 94.8% and 81.5%, respectively. The hospital mortality rates were 0% and 1.9%, respectively, and the complication rates were 33.8% and 44.4%, respectively. With a median follow-up of 28 months (5-38 months), the long-term overall asymptomatic survival rates were 80.5% and 46.3%, respectively. 3D reconstruction preoperative planning was a significant prognostic protective factor of long-term asymptomatic survival for the patients with complicated hepatolithiasis (Cox regression analysis, RR = 0.348, 95% confidence interval 0.185-0.657, p = 0.001). CONCLUSION: Surgical therapy conducted following preoperative planning using 3D reconstruction achieved better clinical outcomes than conventional imaging techniques. Whilst conventional imaging techniques accurately identify intrahepatic stones, they are less capable of identifying bile duct stricture.

Management complicated hepatolithiasis with operative rigid choledochoscope guided by computed tomography (CT)-based 3D reconstruction technique.

BACKGROUND: Treatment of complicated hepatolithiasis is complex and difficult. In this report, we present a novel approach to manage complicated hepatolithiasis using the rigid choledochoscope guided by CT-based 3D reconstruction technique with or without hepatectomy. METHODS: Between February 2012 to December 2013, 25 patients with complicated hepatolithiasis underwent rigid choledochoscope guided by CT-based 3D reconstruction technique combined with or without hepatectomy. 27 patients with complicated hepatolithiasis underwent a traditional operation (traditional method group) from June 2011 to January 2012. All operations were performed by the authors. RESULTS: The final stone clearance rate of the rigid choledochoscope group was 96%, whereas that of the traditional method group was 74.1% (P=0.032). There was no patient died of postoperative mortality in two groups. Moreover, the operative time in the traditional method group was significantly longer than that in the rigid choledochoscope group (P=0.010). Recurrent intrahepatic bile duct stones were not found during the follow-up period in the two groups. CONCLUSIONS: Operative rigid choledochoscope guided by CT-based 3D reconstruction technique combined with or without hepatectomy may be an effective and safe treatment for complicated hepatolithiasis.

[Application of three-dimensional visualization technology in pancreaticoduodenctomy for patients with variant hepatic artery].

OBJECTIVE: To explore the application value of the MI-3DVS in patients with hepatic artery variation receiving duodenopancreatectomy. METHODS: A total of 114 patients who had undergone pancreatoduodenectomy were retrospectively summarized and analyzed during January 2010 to July 2012. The clinical data of 64-slice multidetector CT angiography (64-MDCTA) scanning was introduced into MI-3DVS for procedural segmentation, registration and 3-dimensional reconstruction. Based on the reconstructed 3-dimensional model, the origination and bifurcations of variant hepatic artery was observed. And its anatomical relationships with abdominal organs and vessels were also observed. Thereafter, preoperative procedures planning was formulated. The findings were compared to those found during the operation and by postoperative digital subtraction angiography (DSA) of coeliac artery. RESULTS: The abdominal 3D models can clearly display the size and shape of tumor, the origin and course of the blood vessels, as well as the 3D anatomic relationship between tumors and organs, blood vessels. A total of 14 cases (12.3%, 14/114) were found with variant, including 9 cases (7.9%) with replaced right hepatic artery arising from superior mesenteric artery, 3 cases (2.6%) with replaced common hepatic artery arising from superior mesenteric artery, 2 cases (1.8%) with replaced left hepatic artery arising from left gastric artery. The 14 patients all received standard procedures of duodenopancreatectomy. Compared to the intraoperative findings and postoperative DSA examination, the sensitivity, specificity and accuracy of MI-3DVS to variant hepatic artery is 100%. The preoperative planning guided by MI-3DVS is in line with the intraoperative findings.No postoperative complications occurred in all 14 patients, including hepatic abscesses, biliary fistula and liver failure. CONCLUSIONS: MI-3DVS can accurately diagnose hepatic artery variation before duodenopancreatectomy. Therefore, it contributes to the formulation of preoperative surgical plans.It also increases the success rate of the surgical operations and decreases the occurrence of postoperative complications.

The relationship between CYP2C9 gene polymorphisms and azilsartan metabolism in vitro.

BACKGROUND: The gene polymorphisms of the CYP2C9, as well as the substrate specificity of the enzyme, result in different clearances for different substrates by CYP2C9 variants. RESEARCH DESIGNAND METHODS: The CYP2C9 wild type and 38 CYP2C9 variants, expressed in insectmicrosomes, were incubated with azilsartan. The resulting metabolite,O-desethyl azilsartan, was determined by HPLC-MS/MS. The enzyme kineticparameters of the 38 variants were calculated and compared with the wild type.Subsequently, we selected CYP2C9*1, *2, and *3 as target proteins for molecular docking with azilsartan to elucidate the mechanisms underlying changes in enzyme function. RESULTS: Compared with CYP2C9*1, three variants (CYP2C9*29, *39, and *49) exhibited markedlyincreased CLint values (from 170%-275%, *p < 0.05), whereas 28 variants exhibited significantly decreased CLint values (from 3-63%,*p < 0.05). The molecular docking results showed that the binding energy of CYP2C9*2 and *3 was lower than that of the wild type. CONCLUSION: Thisassessment revealed the effect of CYP2C9 gene polymorphisms on azilsartan metabolism, establishing a theoretical basis for further in-vivo studies and clinical applications. This study will help expand the database of CYP2C9 gene-drug pairs and identify appropriate treatment strategies for azilsartan, contributing to the field of precision medicine.

Construction of a three-dimensional model of renal stones: comprehensive planning for percutaneous nephrolithotomy and assistance in surgery.

OBJECTIVES: To construct a three-dimensional (3D) model of renal stones to facilitate comprehensive planning for percutaneous nephrolithotomy (PCNL) and to assist in surgery. METHODS: Fifteen patients with complex renal stones, including one patient with a horseshoe kidney, eight patients with partial/complete staghorn, and six patients with multiple renal stones, participated in our study. Computed tomography images of the unenhanced, arterial, venous, and excretory phases were obtained before surgery. Image segmentation and 3D reconstruction of the renal stones were performed using Mimics 12.1 software. A virtual safe and reliable percutaneous renal access route were established for each patient by comprehensive planning based on the 3D model of renal stones. PCNL was subsequently performed with the assistance of the 3D model. Patient demographics, surgical details, and postoperative treatment parameters were recorded. RESULTS: The 3D models of renal stones accurately represented the interrelationships between the intrarenal arteries and veins, collecting system, stones, and adjacent anatomical structures. PCNL was completed successfully in all 15 patients. The mean operating time was 75.6 ± 13.4 min. The change in hemoglobin concentration was 1.2 ± 0.3 g/l. The one-stage stone-free rate was 93.3%, and the final stone-free rate was 100%. No major postoperative complications were noted, except for postoperative pain in one case. CONCLUSION: Construction of a 3D model of renal stones with the aim of minimizing the risks of percutaneous procedures and achieving higher one-stage stone-free rates is feasible for comprehensive PCNL planning and assistance in patients with complex renal stones.

Combinatorial Structural Engineering of Multichannel Hierarchical Hollow Microspheres Assembled from Centripetal Fe/C Nanosheets to Achieve Effective Integration of Sound Absorption and Microwave Absorption.

Electromagnetic radiation and noise pollution are two of the four major environmental pollution sources. Although various materials with excellent microwave absorption performances or sound absorption properties have been manufactured, it is still a great challenge to design materials with both microwave absorption and sound absorption abilities due to different energy consumption mechanisms. Herein, a combination strategy based on structural engineering was proposed to develop bi-functional hierarchical Fe/C hollow microspheres composed of centripetal Fe/C nanosheets. Both of the interconnected channels created by multiple gaps among the adjacent Fe/C nanosheets and the hollow structure have positive effects on the absorbing performances by promoting the penetration of microwaves and acoustic waves and prolonging action time between microwave energy and acoustic energy with materials. In addition, a polymer-protection strategy and a high-temperature reduction process were applied to keep this unique morphology and further improve the performances of the composite. As a result, the optimized hierarchical Fe/C-500 hollow composite exhibits a wide effective absorption bandwidth of 7.52 GHz (10.48-18.00 GHz) at only 1.75 mm. Furthermore, the Fe/C-500 composite can effectively absorb sound wave in the frequency of 1209-3307 Hz, basically including part of the low frequency range (<2000 Hz) and most of the medium frequency range (2000-3500 Hz), and has 90% absorption of sound at 1721-1962 Hz. This work puts new insight into the engineering and development of microwave absorption-sound absorption-integrated functional materials with promising applications.

A novel UHPLC‒MS/MS method for quantitative analysis of zanubrutinib in rat plasma: application to an in vivo interaction study between zanubrutinib and triazole antifungal.

BACKGROUND: This study establishes a UHPLC‒MS/MS method for the detection of zanubrutinib and explores its interaction with fluconazole and isavuconazole in rats. METHODS: A protein precipitation method using acetonitrile was used to prepare plasma samples using ibrutinib as an internal standard. Chromatographic separation and mass spectrometric detection of the analytes and internal standards were performed on a Shimadzu 8040 UHPLC‒MS/MS equipped with a Shim-pack velox C18 column (2.1 × 50 mm, 2.7 µm). Methanol and 0.1% formic acid-water were used as mobile phases. Intraday and interday precision and accuracy, extraction recoveries, and matrix effects of this method were determined. The linearity and sample stability of the method were assessed. Eighteen male Sprague‒Dawley (SD) rats were randomly divided into three groups with zanubrutinib (30 mg/kg) alone, zanubrutinib in combination with fluconazole (20 mg/kg) or zanubrutinib in combination with isavuconazole (20 mg/kg). Blood samples (200 µL) were collected at designated time points (ten evenly distributed time points within 12 h). The concentration of zanubrutinib was determined using the UHPLC‒MS/MS method developed in this study. RESULTS: The typical fragment ions were m/z 472.15 → 290.00 for zanubrutinib and m/z 441.20 → 138.10 for ibrutinib (IS). The range of the standard curve was 1-1000 ng/mL with a regressive coefficient (R2) of 0.999. The recoveries and matrix effects were 91.9-98.2% and 97.5-106.3%, respectively, at different concentration levels. The values for intra- and interday RSD% were lower than 9.8% and 5.8%, respectively. The RSD% value was less than 10.3%, and the RE% value was less than ± 4.0% under different storage conditions. Analysis of pharmacokinetic results suggested that coadministration with isavuconazole or fluconazole significantly increased the area under the curve (1081.67 ± 43.81 vs. 1267.55 ± 79.35 vs. 1721.61 ± 219.36), peak plasma concentration (332.00 ± 52.79 vs. 396.05 ± 37.19 vs. 494.51 ± 130.68), and time to peak (1.83 ± 0.41 vs. 2.00 ± 0.00 vs. 2.17 ± 0.41) compared to zanubrutinib alone. CONCLUSION: This study provides information to understand the metabolism of zanubrutinib with concurrent use with isavuconazole or fluconazole, and further clinical trials are needed to validate the results in animals.

Effect of apatinib on the pharmacokinetics of tramadol and O-desmethyltramadol in rats.

Since the combination of anticancer drugs and opioids is very common, apatinib and tramadol are likely to be used in combination clinically. This study evaluated the effects of apatinib on the pharmacokinetics of tramadol and its main metabolite O-desmethyltramadol in Sprague-Dawley (SD) rats and the inhibitory effects of apatinib on tramadol in rat liver microsomes (RLMs), human liver microsomes (HLMs) and recombinant human CYP2D6.1. The samples were determined by ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). The in vivo results showed that compared with the control group, apatinib increased the AUC(0-t), AUC(0-∞) and Cmax values of tramadol and O-desmethyltramadol, and decreased the values of VZ/F and CLz/F. In addition, the MRT(0-t), MRT(0-∞) values of O-desmethyltramadol were increased. In vitro, apatinib inhibited the metabolism of tramadol by a mixed way with IC50 of 1.927 µM in RLMs, 2.039 µM in HLMs and 15.32 µM in CYP2D6.1. In summary, according to our findings, apatinib has a strong in vitro inhibitory effect on tramadol, and apatinib can increase the analgesic effect of tramadol and O-desmethyltramadol in rats.

Anatomical variations of hepatic veins: three-dimensional computed tomography scans of 200 subjects.

BACKGROUND: The impact of hepatic venous anatomic variations on hepatic resection and transplantation is the least understood aspect of liver surgery. METHODS: A prospective three-dimensional computed tomography study was undertaken on 200 consecutive subjects with normal livers to determine the prevalence of surgically significant hepatic venous anatomic variations. RESULTS: The prevailing pattern of the three hepatic veins in these subjects was a right hepatic vein (RHV) and a common trunk for the middle (MHV) and left (LHV) hepatic veins (122/200, 61%). The remaining patients had the RHV, MHV, and LHV draining independently into the inferior vena cava (IVC). In 39% of patients, the RHV was small and was compensated by a large right inferior hepatic vein (21.0%), an accessory RHV (8.5%) or a well-developed MHV (6.5%). A segment 4 vein was seen in 51.5% of patients. This segment 4 vein joined the LHV (26%), the MHV (17.5%), or the IVC (8%). An umbilical vein and a segment 4 vein were seen in 3.5% of patients. These two veins joined either the LHV (2.0%) or the MHV (1.5%). CONCLUSIONS: Knowing the variations of hepatic veins before surgery is useful during both partial hepatectomy and donor operations for living related liver transplantation.

Rational design of two-dimensional flaky Fe/void/C composites for enhanced microwave absorption properties.

Owing to their unique electromagnetic properties and structure anisotropy, two-dimensional (2D) magnetic metal flakes are attracting special attention for applications as microwave absorption materials. However, the conductive network formed by the connected metal flakes may lead to impedance mismatching and reduced performance. In this study, a facile and rational strategy was developed to fabricate yolk-shell-structured 2D flaky Fe/void/C composites by using α-Fe2O3 hexagonal flakes as the template, followed by the coating of polydopamine (PDA) on the composite surface and calcination under H2/Ar. The volume shrinkage from Fe2O3 to Fe and PDA to carbon led to the formation of several irregular holes in Fe flakes and void space between the Fe cores and carbon cages. The thickness of carbon cages of the composites can be tailored by the simple modulation of the synthetic parameters. As a result of the synergistic effects of multiple chemical components, the shape anisotropy of iron flakes, and unique yolk-shell structures, the optimized sample exhibited excellent microwave absorption properties. With a matching thickness of only 1.6 mm, the strongest reflection loss (RL) was up to -27.80 dB at 14.72 GHz, and the effective absorption bandwidth (EAB, RL < -10 dB) reached 6.40 GHz (11.60-18.00 GHz), which can cover the whole Ku-band. This study provides a novel approach to adjust and balance the permeability and permittivity of 2D magnetic metal flakes, which may promote the practical applications of flaky magnetic metal materials in microwave absorption.

Development and Validation of a UHPLC-MS/MS Method for Quantitation of Almonertinib in Rat Plasma: Application to an in vivo Interaction Study Between Paxlovid and Almonertinib.

Almonertinib was approved for the first-line treatment of advanced NSCLC patients with EGFR-TKI-sensitive genetic mutations by National Medical Products Administration (NMPA) in 2021.The purpose of this study was to establish and validate a fast, accurate, stable and facile ultra-performance liquid chromatography-tandem mass spectrometry method for the quantification of almonertinib in rat plasma, it was employed to explore the effect of Paxlovid on the pharmacokinetics of almonertinib in rats. Zanubrutinib was used as an internal standard (IS), and the plasma samples were prepared by the protein precipitation method using acetonitrile. Chromatographic separation was carried out on a Shimadzu LC-20AT ultra-performance liquid chromatography system using a Shim-pack velox C18 (2.1× 50 mm, 2.7 µM) column. The mobile phase consisted of methanol and 0.1% formic acid-water. Mass spectrum analysis was executed using Shimadzu 8040 Triple quadrupole mass spectrometry. The precursor and product ions of the analyte and internal standard were detected in multiple reaction monitoring (MRM) mode. The typical fragment ions were m/z 526.20 → 72.10 for almonertinib and m/z 472.15 → 290.00 for zanubrutinib (IS). The method was validated to have good linearity for quantifying almonertinib in rat plasma from 0.1-1000 ng/ml (R2 = 0.999), and the LLOQ was 0.1 ng/ml. The validity of this method was sufficiently verified for selectivity, specificity, extraction recovery, matrix effect, accuracy, precision and stability. The validated UHPLC-MS/MS method was successfully applied to the drug interaction study of almonertinib with Paxlovid in rats. Paxlovid significantly inhibits the metabolism of almonertinib and increased the exposure of almonertinib. This study can help us to understand the metabolic profile of almonertinib better, and further human trials should be conducted to validate the results.

[Application of the medical image three-dimensional visualization system of abdomen in diagnosis and evaluating resectability of pancreatic tumors].

OBJECTIVE: To study the value and the clinical application of the Medical Image three-dimensional Visualization System of Abdomen (MI-3DVS) in diagnosis and evaluating resectability of pancreatic tumor. METHODS: Twelve patients with pancreatic tumor were tested with 64-slice helical CT (64-MSCT) angiography, and the CT data was reconstructed with MI-3DVS from November 2008 to August 2009. The 3D findings were adopted in diagnosis and evaluating resectability, and the results were compared with surgical operation and the pathological finding. There were 7 male and 5 female, aged from 14 to 83 years. Within the 12 cases, there were 4 cases with pancreatic carcinoma, 5 cases with pancreatic solid pseudopapillary tumor, 2 cases with pancreatic serous cystadenoma, 1 case with pancreatic cyst (ductal epithelial papillary hyperplasia). RESULTS: Nine tumors which had been regarded as removable pre-operatively with MI-3DVS were removed successfully. Three patients who were considered unresectable by other hospitals with CT were operated successfully with MI-3DVS. The other 3 patients' tumors were actually not able to be removed as pre-operative evaluation. CONCLUSION: MI-3DVS plays an important role in diagnosis and assessment of resectability of pancreatic tumor.

Synthesis of sandwich-like Co15Fe85@C/RGO multicomponent composites with tunable electromagnetic parameters and microwave absorption performance.

Magnetic particle/carbon hybrid structures are promising candidates for high performance microwave absorbing materials with light weight and strong absorption. However, it remains a great challenge to balance the permittivity and permeability to realize impedance matching and further improve their absorption bandwidth. Herein, an effective strategy is designed to fabricate sandwich-like Co15Fe85@C/RGO composites. By introducing RGO sheets in the hybrid structures, the electromagnetic parameters, impedance matching and microwave absorption properties of the final materials can be well controlled. The optimized Co15Fe85@C/RGO composite shows an excellent microwave absorption performance, the strongest reflection loss (RL) of the sample is up to -33.38 dB at 10.72 GHz with a matching thickness of 2.5 mm, and the effective bandwidth (RL < -10 dB) can reach 9.2 GHz (8.64-17.84 GHz). With a single thickness, such a wide absorption band is rarely reported. Their excellent performance can be ascribed to the synergetic effect of the chemical composition and unique sandwich-like structures, which will improve impendence matching and strong microwave attenuation constants of the composites. Our results provide a facile strategy for tuning the electromagnetic parameters and microwave absorption properties of magnetic metal/carbon hybrid structures.

[Study on visualized virtual surgery of living-related donor liver transplantation].

OBJECTIVE: To investigate the significance of three dimensional visualization and virtual surgery system in living related donor liver transplantation surgery. METHODS: Two patients suffered biliary calculi were scanned by 64 slice helical computer tomography (CT) on livers and the data were imported into medical image proceeding system (MIPS) for sequence. Man-made segmentation and true-up on the image from the data were carried out. Three dimensional (3D) models of the liver and the intrahepatic vessels were reconstructed by VTK software respectively. The models were exported with format STL from it and then were imported into the FreeForm Modeling System for smoothing and modifying. At last, living related donor liver transplantation were simulated with the force-feedback equipment (PHANToM). RESULTS: It had great verisimilar image for the reconstructed 3D liver models with artery, hepatic vein, portal vein and bile duct. By seeing through liver, it had high fidelity and strong 3D effect for the intrahepatic artery, hepatic vein, portal vein and bile duct, and their spatial disposition and course and co-relationship were shown clearly. In the virtual surgery system, the virtual scalpel could be manipulated on 3D liver model with PHANToM. The simulating effect was the same as the clinic operation for living related donor liver transplantation. CONCLUSIONS: The visualized liver model reconstructed is 3D and verisimilar, and it is helpful to design reasonable scheme for liver transplantation. It can improve the surgical effect, decrease the surgical risk, reduce the complication, enhance the communication between doctor and patient through designing surgical plan and demonstrating visualized operation before surgery.

Inhibitory Mechanisms of Myricetin on Human and Rat Liver Cytochrome P450 Enzymes.

BACKGROUND AND OBJECTIVES: Myricetin is a flavonoid compound that is abundant in teas, red wine, berries, herbs and vegetables with a variety of pharmacological properties such as antioxidant, anti-inflammatory and anti-cancer effects. Although there are in vitro studies showing that myricetin inhibits human cytochrome P450 (CYP) 2D6 and CYP3A, the inhibitory mechanisms of myricetin on CYP enzymes are still unclear. The aim of this study was to evaluate the inhibitory effects of myricetin on human and rat CYPs, including CYP3A2/3A4, CYP2B1/2B6, CYP2C9/2C11 and CYP2D1/2D6. METHODS: This study was performed to investigate the inhibitory effects of myricetin on human CYP3A4, CYP2B6, CYP2C9, CYP2D6 and rat CYP3A2, CYP2B1, CYP2C11, CYP2D1 through the cocktail approach using ultra-performance liquid chromatography tandem mass spectrometry. Typical probe substrates were used as follows-midazolam for CYP3A2/3A4, dextromethorphan for CYP2D1/2D6, tolbutamide for CYP2C9/2C11, and bupropion for CYP2B1/2B6. RESULTS: The results of this study showed that myricetin might not be a time-dependent inhibitor. Moreover, myricetin inhibited CYP3A4 in an uncompetitive way with an inhibition constant (Ki) value of 143.1 µM. It was also a noncompetitive inhibitor of CYP2C9 and CYP2D6 with Ki values of 31.12 and 53.44 µM and a competitive inhibitor of CYP2B1 with a Ki value of 69.70 µM, as well as a mixed inhibitor of CYP3A2, CYP2C11 and CYP2D1with Ki values of 37.57, 14.88 and 17.39 µM, respectively. CONCLUSIONS: In conclusion, this study indicates that myricetin inhibited CYP3A4/3A2, CYP2C9/2C11, CYP2D6/2D1 and CYP2B1 by various mechanisms with different Ki values. Given that our experiments are established in vitro, further in vivo work is needed to confirm the interaction between myricetin and CYP enzymes, thus providing better guidance for the safe clinical use of myricetin.

[Study on the three dimensional hepatic virtual operation based on the data of 64-slice helical CT scanning].

OBJECTIVE: To study the surgery plan and simulation effect of the three dimensional (3D) hepatic virtual operation based on the data of 64-slice helical CT scanning and to probe the feasibility of the virtual operation based on the FreeForm Modeling System. METHODS: The volunteer liver was scanned to collect two dimensional (2D) DICOM data of 64-slice helical CT scanning and the 3D hepatic and intrahepatic vessels model were reconstructed by MIMICS software. The reconstructed liver, the intrahepatic vessels model and the artificial tumor models were output into the FreeForm Modeling System in the STL format. The device PHANTOM with the characterization of dynamo-feedback was applied to make the operation on the 3D hepatic. RESULTS: The spatial relationship between the tumour and the intrahepatic vessels were clearly observed by rotation and enlargement of the target. According to the operation principle, the left lobe of liver resection was simulated by manipulating the device PHANToM. Through the liver transparence surface, the intrahepatic vessels were easily distinguished. The operation procedure was accord with the clinic hepatic surgery. Meanwhile, during the operation, by adjusting the incision objective intensity, the dynamo-feedback intensity was definitely touched. CONCLUSIONS: By using the FreeForm Modeling System,the hepatic operation procedure can be simulated ahead of time. The operation complication in the practical surgery can be anticipated and the individualization operation schema can be reasonable instituted.