OBJECTIVETo select the best preparation method of vincristine transfersomes (VCR-T) and predict its possibility of being a new formulation of VCR.

METHODOrthogonal design was used to optimize the preparation methods on the basis of single factor pretests; and the permeation tests in vitro were performed in modified Franz diffusion cells.

RESULTThe optimum formula was: pH was equal to 7.3, the ratio of lecithin to sodium deoxycholate is 70/20, the weight of VCR is 10 mg, hydrating time is 30 minutes. The optimized solution was light yellow and transparent colloid solution. The VCR-T are spherical and smooth with average diameters of 94 nm and an encapsulation ratio of 90%. The test in vitro showed that VCR-T could permeat through mouse skin at zero rate with the cumulative penetrating quality amounting to 63.8%.

CONCLUSIONTransfersomes may become a promising carrier of VCR for clinic use.

Administration, Cutaneous ; Animals ; Antineoplastic Agents, Phytogenic ; administration & dosage ; pharmacokinetics ; Deoxycholic Acid ; Drug Carriers ; Hydrogen-Ion Concentration ; Mice ; Particle Size ; Phosphatidylcholines ; Skin Absorption ; Technology, Pharmaceutical ; methods ; Vincristine ; administration & dosage ; pharmacokinetics

OBJECTIVETo study the liver targeted drug delivery system of TBMS--the effective anticancer component from Bolbstemma paniculatum, and to discuss the system's function of decreasing toxicity.

METHODBCA was used as carrier material. The preparation through overall feedback dynamic techniques. The properties of preparation and toxicology were also technology of nanoparticles was optimized studied. Thenanoparticles' targeting in mice vivo was observed with transmission electron microscopy. The function of decreasing toxicity was researched by the XXTX-2000 automatic quantitative analysis management system.

RESULTD50 was 0.68 microm. Drug-loading rate and entrapment rate were 37.3% and 88.6% respectively. The release in vitro accorded with Weibull equation. The reaching release balance time and the t 1/2 extended 26 times and 19 times respectively comparing with injection. Nanoparticles mainly distributed in liver tissue. Their toxicity to lung and liver was evidently lower than injection. Nanoparticles' LD50 exceeded injection's by 13.5% and their stimulus was much lower than injection.

CONCLUSIONThe TBMS can be targeted to liver by liver targeted drug delivery system. At the same time, the problem about the toxicity hindering clinical application could be solved, which lays the foundation for the further studies on TBMS.

Animals ; Antineoplastic Agents, Phytogenic ; administration & dosage ; pharmacokinetics ; Cucurbitaceae ; chemistry ; Delayed-Action Preparations ; Drug Compounding ; methods ; Drug Delivery Systems ; Drugs, Chinese Herbal ; administration & dosage ; pharmacokinetics ; Excipients ; Liver ; metabolism ; Mice ; Nanostructures ; Particle Size ; Plants, Medicinal ; chemistry ; Rabbits ; Rhizome ; chemistry ; Tissue Distribution

This study was aimed to investigate the protective effects of dimethylsulfoxide (DMSO) combined with trehalose on the cryopreserved platelets. The platelets were preserved at -80 degrees C. The experiments were divided into 5 groups: blank control group composed of apheresis platelet suspension; trehalose group composed of apheresis platelet suspension and 0.25 mol/L trehalose; DMSO group composed of apheresis platelet suspension and 5% DMSO; 5% combined group composed of apheresis platelet suspension, 5% DMSO and 0.25 mol/L trehalose; 2.5% combined group composed of apheresis platelet suspension, 2.5% DMSO and 0.25 mol/L trehalose. All the groups were thawed at 37 degrees C in a waterbath. The recovery rate of platelets and mean platelet volume (MPV) were assayed by using hemocytometer; the ultrastructural changes were examined by electron microscopy; the expressions of CD41, CD42b, CD61 and CD62p on platelets were detected by flow cytometry. The results indicated that single use of trehalose had no strong effect in increasing the recovery rate of platelets, but the morphology of platelets was close to normal. The DMSO showed significant effect in increasing the recovery rate of platelets and maintaining the intact property of platelets, however, the shape of platelets tended to sealing, and partial platelets still displayed heteromorphic changes. The combination of DMSO and trehalose revealed the protective effect on the external morphology and internal structure of platelets to be close to the normal homeostasis, and ensured an ideal recovery rate of the cryopreserved platelets and higher expression levels of CD41, CD42b, CD61 and CD62p in the same time. It is concluded that the combined use of DMSO and trehalose possesses the synergistic protective effect on the cryopreserved platelets, therefore, the combined use of both as the protective agent is hopeful to further raise the effectiveness of clinical infusion of the cryopreserved platelets.
Blood Platelets ; drug effects ; Blood Preservation ; methods ; Cryopreservation ; methods ; Dimethyl Sulfoxide ; pharmacology ; Humans ; Platelet Count ; Trehalose ; pharmacology

BACKGROUNDThis study was to investigate the relationship among aortic artery calcification (AAC), cardiac valve calcification (CVC), and mortality in maintenance hemodialysis (MHD) patients.

METHODSAll MHD patients in Shanghai Ruijin Hospital in July 2011 were included. To follow up for 42 months, clinical data, predialysis blood tests, echocardiography, and lateral lumbar X-ray plain radiography results were collected. Plasma FGF23 level was measured using a C-terminal assay.

RESULTSTotally, 110 MHD patients were involved in this study. Of which, 64 (58.2%) patients were male, the mean age was 55.2 ± 1.4 years old, and the median dialysis duration was 29.85 (3.0-225.5) months. About 25.5% of the 110 MHD patients had CVC from echocardiography while 61.8% of the patients had visible calcification of aorta from lateral lumbar X-ray plain radiography. After 42 months follow-up, 25 (22.7%) patients died. Kaplan-Meier analysis showed that patients with AAC or CVC had a significant greater number of all-cause and cardiovascular deaths than those without. In multivariate analyses, the presence of AAC was a significant factor associated with all-cause mortality (hazard ratio [HR]: 3.149, P = 0.025) in addition to lower albumin level and lower 25-hydroxy Vitamin D (25(OH)D) level. The presence of CVC was a significant factor associated with cardiovascular mortality (HR: 3.800, P = 0.029) in addition to lower albumin level and lower 25(OH)D level.

CONCLUSIONLateral lumbar X-ray plain radiography and echocardiography are simple methods to detect AAC and CVC in dialysis patients. The presence of AAC and CVC was independently associated with mortality in MHD patients. Regular follow-up by X-ray and echocardiography could be a useful method to stratify mortality risk in MHD patients.

Aortic Diseases ; blood ; complications ; Calcinosis ; blood ; complications ; China ; Female ; Fibroblast Growth Factors ; blood ; Follow-Up Studies ; Heart Valve Diseases ; blood ; complications ; Heart Valves ; pathology ; Humans ; Male ; Middle Aged ; Proportional Hazards Models ; Renal Dialysis ; mortality

To address the issue of peak loss when applying variational mode decomposition(VMD)to denoise spectra with sharp peaks,in this study,a method for spectral signal denoising of complex samples called peak extraction variational mode decomposition(PE-VMD)was introduced.Firstly,the spectral signal was subjected to a process of denoising utilising the VMD algorithm.Next,the first order derivatives of the spectral signals were calculated to determine the peak center.Subsequently,the second order derivatives of the spectral signal was calculated to extract the sharp peaks with high signal-to-noise ratio(SNR).Finally,the peak intercepted that lose information after VMD denoising were removed,and the remaining spectrum was sequentially connected with the extracted sharp peaks to obtain the final denoised spectrum.The effectiveness of the method was evaluated by one of simulated signals and X-ray diffraction(XRD)spectrum of MnCo-ISAs/CN catalysts.Furthermore,the method was compared with other denoising techniques,including Savitzky-Golay(SG)smoothing,empirical mode decomposition(EMD)and VMD.The efficacy of the denoising process was then assessed by analyzing the spectrograms and signal-to-noise ratio before and after denoising.The results demonstrated that PE-VMD denoising achieved the greatest SNR and effectively preserved the essential information of the spectral signals.Consequently,PE-VMD exhibited superior denoising capability for spectra with sharp peaks.

Aim To investigate the intracellular up-take and target protein binding characteristics of two Bruton's tyrosine kinase inhibitors(BTKi)with differ-ent selectivities to provide further insights into the mechanisms of drug off-target-related bleeding risk.Methods Ibrutinib(non-selective BTKi)and za-nubrutinib(selective BTKi)were used as study drugs.After incubation of MEC-1 cells and human platelets with drugs,the cellular thermal shift assay(CETSA)was combined with Western blot to obtain the melting curve and isothermal curve to analyze the binding char-acteristics of the two drugs with the target protein BTK.After incubation of MEC-1 cells and human platelets with drugs,the concentrations of the two drugs were detected by liquid chromatography-tandem mass spectrometry(LC-MS/MS)to analyze the intracellular uptake of the two drugs.Results CETSA analysis confirmed that zanubrutinib was more selective for the target protein BTK compared to ibrutinib.LC-MS/MS analysis showed that both drugs were uptaken intracel-lularly by MEC-1 cells and platelets in a concentration-dependent manner.Conclusions While BTKi targe-ting BTK to B lymphocytes exerts therapeutic effects,off-target effects on platelets due to differences in their intracellular uptake,and target-binding characteristics may be one of the reasons for the differences in bleed-ing risk across selective BTKi.

Twelve flavonoids were isolated and purified from the ethyl acetate fraction of 95% ethanol extract of Dalbergia odorifera by heat reflux extraction, solvent extraction, recrystallization, normal phase silica gel, Sephadex LH-20, MCI gel and HPLC methods. The structures were identified with multiple spectroscopic methods, including 1 D-NMR, 2 D-NMR and MS. The compounds were identified as 6,7,8-trimethoxy-5,4'-dihydroxy isoflavone(1), medicarpin(2), 7,2'-dihydroxy-4'-methoxy-isoflavanol(3), biochanin A(4), prunetin(5), genistein(6), pratensein(7), 3-(4-hydroxyphenyl)-6-isopentenyl-7-methoxy-4H-chromen-4-one(8), tectorigenin(9), irisolidone(10), vestitol(11), and formononetin(12). Compound 1 was a new isoflavone, and compound 8 was isolated from D. odorifera for the first time. The results showed that compounds 1-3 had inhibitory effects on tyrosinase, with inhibition rates of 35.58%, 38.63% and 51.34% at the concentration of 1.0 mmol·L~(-1), respectively.
Dalbergia/chemistry* ; Ethanol ; Flavonoids/chemistry* ; Genistein ; Isoflavones/pharmacology* ; Monophenol Monooxygenase ; Plant Extracts/pharmacology* ; Silica Gel ; Solvents

OBJECTIVEThe effects of primary percutaneous coronary intervention (PCI) in patients with acute myocardial infarction (AMI) induced by left main (LM) artery occlusion were analyzed retrospectively in this study.

METHODSA total of 1343 consecutive AMI patients who underwent primary PCI between January 1995 and December 2004 were retrospectively studied.

RESULTSLM occlusion or severe stenosis were found in 11 patients [all male, mean age (56.4 +/- 9.2) years (range 43-70 years)], cardiogenic shock was overt in 6 patients. Primary PCI were performed under the assistance of intra-aortic balloon pump (IABP) in these patients [8 stent implantation, 3 balloon dilation and 2 necessitating emergency CABG after balloon dilation]. In-hospital mortality was 45.5% (5/11). Three-month follow-up were made in all survivals (6/11). Analysis showed good collateral circulation flow from right coronary artery to left coronary artery was existed in all survival cases before PCI.

CONCLUSIONPrognosis of AMI patients with LM artery obstruction or severe stenosis was poor. Patients with pre-existed collateral circulation before primary PCI and IABP had a better clinical outcomes.

Adult ; Aged ; Angioplasty, Balloon, Coronary ; Arterial Occlusive Diseases ; complications ; Coronary Stenosis ; complications ; Emergency Treatment ; Follow-Up Studies ; Humans ; Male ; Middle Aged ; Myocardial Infarction ; etiology ; therapy ; Prognosis ; Retrospective Studies

Anticoagulants ; Female ; Heparin ; Humans ; Pregnancy ; Pulmonary Embolism/diagnostic imaging* ; Thrombocytopenia

Objective To investigate the effect of nobiletin on platelet-activating factor(PAF)metabolism in diabetic rats with renal injury.Methods Totally 72 rats were randomly divided into control group(n=10)and modeling group(n=62).The modeling group rats were induced to develop a diabetic rat model with renal injury and then further divided into the model group,aspirin group(20 mg/kg),and nobiletin low(50 mg/kg),medium(100 mg/kg),and high-dose(200 mg/kg)groups,each with 10 rats.After continuous oral administration for 6 weeks,rat body weight,kidney weight,and kidney index were measured.Histopathological assessments were conducted by using HE,periodic acid-Schiff staining(PAS),Masson staining,and transmission electron microscopy.Blood glucose levels,renal function,inflammatory factors,PAF and its regulatory factors were detected.Expression levels of PAF metabolism-related proteins,PAF-acetylhydrolase(PAFAH),PAF receptor(PAFR),and cholinephosphotransferase 1(CHPT1)in kidney tissues were assessed using Western blotting and immunohistochemistry.Results Following nobiletin intervention,rat body weight increased while kidney weight and kidney index decreased.Improvement in renal tissue pathology was observed,with reduced interstitial fibrosis and thinner basement membrane.Fasting blood glucose and glycated hemoglobin decreased,while fasting insulin showed no significant improvement.Urea nitrogen,blood creatinine,cystatin C,and 24-hour urinary protein excretion were reduced.Levels of interleukin(IL)-1α,IL-6,IL-8,and tumor necrosis factor(TNF-α)were lowered.PAF and its regulatory factors decreased.PAFR and CHPT1 expression decreased,while PAFAH increased.Conclusion Nobiletin can alleviate renal injury in diabetic rats with renal injury,improve kidney function,regulate blood glucose,and mitigate inflammatory response.Its mechanism may be associated with the modulation of platelet-activating factor metabolism.