There is a broad and urgent need for the clinical application of anticancer nanomedicine in tumor therapy, but the complex biological barrier in solid tumors has always been the main obstacle to infiltrating nanomedicine into the tumor. The traditional design of nanomedicine based on enhanced permeability and retention (EPR) effect still has some limitations in tumor permeability, it is urgent to find other design theories. Therefore, this review summarizes two novel strategies, active transcytosis and immune cell-mediated tumor penetration, for promoting tumor penetration of anticancer nanomedicine.

Objective To establish an UPLC method for determination of Triptolide in serum and explore its pharmacokinetics in patients with rheumatoid arthritis after oral administration of tripterygium glycosides tablet. Methods Three patients with rheumatoid arthritis were enrolled. Using Estazolam as internal standard, serum was extracted with acetic ether, and determination was performed on column of Waters Acquity C18 (2.1 mm×100 mm, 1.7 μm) with mobile phase consisted of acetonitrile-0.1% glacial acetic acid (30∶70) at the flow rate of 0.2 mL/min. The column temperature was 30 ℃, and the detection wavelength was set at 220 nm. The serum concentration of Triptolide was processed by DAS 2.1.1 computer program. Results Triptolide was well-separated from internal standard, and the retention time were about 4.9 min and 8.9 min, respectively. Linear range of Triptolide was 13.13-840.00 ng/mL. RSD of intra-day and inter-day were lower than 15%and the recoveries were 88.25%-99.33%. Pharmacokinetic parameters were as follows:Cmax was (159.97±42.43) ng/mL, Tmax was (1.33±0.58) h, T1/2βwas (7.51±2.26) h, and AUC0-12 h was (1131.12±89.20) mg?h/L, respectively. Conclusion Pharmacokinetics of Triptolide conformed to two compartment model. Triptolide can be quickly absorbed, and exists differences among individuals.

Objective To study the applications and outcomes of using autogeneic cartilage in hearing recon-struction surgery in patients with chronic otitis media or cholesteatoma .Methods A total of 165 patients (173 ears) in whom autogeneic cartilage was used were analyzed retrospectively .Forty -three patients (48 ears) had simple tympanic membrane perforations ,61 patients (61 ears) had cholesteatomas including 12 retraction pockets ,23 pa-tients (23 ears) had tympanoscleroses and 38 patients (41 ears) had otitis media with granulations .The cartilage grafts were used for tympanic perforation reparing in 133 patients (139 ears) ,for ossiculoplasty in 102 patients (104 ears) ,for attic reconstruction in 31 patients (31 ears) and for canal wall reconstruction of external auditory canal in 3 patients (3 ears) .The auditory outcome (0 .5 ,1 ,2 ,and 4 kHz pure tone average hearing threshold ,the average air-bone gap) and local architecture status were followed up for 1 year after surgery .Results In 133 patients (139 ears) with tympanic perforation ,the rate of successful repair of a tympanic membrame perforation in one -stage was 97 .84% with perforation repair in 136 ears and postoperative perforation in 3 ears .In 102 patients (104 ears) of os-siculoplasty ,there was no ossicular prostheses prolapse .In 31 patients (31 ears) of attic reconstruction ,no local graft shift or collapse was found .In 3 patients (3 ears) of external auditory canal repair ,no canal wall collapse occurred . In myringoplasty group (43 patients ,48 ears) ,preoperative and postoperative air -bone gap (ABG) was 23 .8 ± 3 .1 dB and 11 .6 ± 8 .7 dB ,respectively .In cholesteatoma group (61 patients ,61 ears ) ,preoperative and postoperative ABG were 39 .2 ± 24 .7 dB and 19 .0 ± 12 .1 dB ,respectively .In tympanosclerosis group (23 patients ,23 ears) ,pre-operative and postoperative ABG were 31 .2 ± 12 .4 dB and 19 .8 ± 11 .2 dB ,respectively .In otitis media with granu-lation group (38 patients ,41 ears) ,preoperative and postoperative ABG were 41 .6 ± 9 .9 dB and 15 .3 ± 13 .4 dB ,re-spectively .Conclusion Autogeneic cartilage is very valuable in hearing reconstruction surgery ,especially in compli-cated tympanic perforation ,combination with ossiculoplasty prostheses ,or reconstruction of mastoid cavity or exter-nal call wall defect .

The transesterification reaction conditions of lard with methyl acetate with combined use of immobilized lipases as catalysts were conducted. Initially, according to single factorial experiments, the studies on Lipozyme TL IM and Novozym 435 respectively catalyzed transesterification of lard showed that the optimal parameters of transesterification reaction were: the molar ratio of methyl acetate to oil of 14∶1, 40% enzyme added based on oil weight, temperature 50℃. Combined use of Lipozyme TL IM and Novozym 435 was proposed further to improve the catalytic performance by the response surface method (RSM). Herein, a 5-level-3-factor central composite rotated design was employed to evaluate the effects of lipase loading, the proportion of the two lipases and amount of methyl acetate. The optimum conditions were as followings: 40% lipase loading based on oil weight, 50%/50% the proportion of lipases (Novozym 435/Lipozyme TL IM), and the molar ratio of methyl acetate to oil of 14∶1. And under the optimal conditions, the highest biodiesel yield of 97.6% could be attained, which was higher than the biodiesel yield with each single one of the two lipases. The results suggested that the technics of combined use of certain immobilized lipases catalyzed transesterification reaction of lard for biodiesel production with methyl acetate as the acyl acceptor could raise the FAME yield and save the production cost.

Objective To analyze comparatively the outcome of modified Manipal and DeVega tricuspid annuloplaaty.Methods From Oct.2001 to Aug.2004,the consecutive 123 patients operated with modified Manipal tricuspid annuloplasty for tricuspid re- gurgitation at the time of left cardiac valve replacement(group A)were elected in this study.The other 174 patients operated with De Vega tricuspid annuloplasty at the time of left cardiac valve replacement were elected randomly for control(group B).There were no significant differences of the patient data before surgery between two groups.Results There were overall 11 early deaths(4 in group A,7 in group B),The overall in-hospital mortality rate was 3.7 %.215 of the 286 surviving patients were followed;the overall follow up was 75.2 %.Mean follow-up was(28.4?9.1)months(range from 13 to 49 months).There were ten late deaths and the late mortality rate was 4.7%.There was no significant differences in the patients with 3+～4+ tricuspid regurgitation at follow-up 18,30 and 42 months in group A;but there was an increase of the patients with 3+～4+ tricuspid regurgitation with an incremental follow up term in group B(P

Objective The study is to investigate the role of miR-328 in endothelial mesenchymal transition (EMT)induced by high glucose in human umbilical vein endothelial cells (HUVECs)and its signaling mechanism.Methods HUVECs were cultured in high glucose environment to induce EMT;The recombinant lentiviruses were created by miR-328 and antagomiR- 328 transfection of HUVECs.The experiment was divided into seven groups: normal glucose;mannitol group;high glucose;miR-328;miR-328 virus negative control;high glucose + U0126;miR-328 + U0126.Double immunofluorescent staining was used to determine expression of EMT markers;Changes in miR-328 expression is examined by RT-qPCR;The expressions of type Ⅰ/Ⅲ collagen,p-MEK1/2 and p-ERK1/2 are examined by Western blot.Results 1)HUVECs showed positive staining for CD31 and α-SMA in high glucose group.2)The expression of miR-328 was up-regulated(P<0.05)in HUVECs treated by high glucose or miR-328.Compared with high glucose group or miR-328 group,miR-328 expression was less pronounced aftertreatment with U0126.3)The expressions of type Ⅰ/Ⅲ collagen increased in HUVECs treated by high glucose or miR-328(P<0.05) Compared with high glucose group or miR-328 group,typeⅠ/Ⅲ collagen expressions were less pronounced after treatment with U0126.4)The expressions of p-MEK1/2 and p-ERK1/2 were increased in HUVECs treated by high glucose or miR-328 in comparison to the control group (P<0.05);a lower expression of p-MEK1/2 and p-ERK1/2 were observed in U0126 group than in high glucose group or miR-328 group.Conclusions The phenomenon of EMT in HUVECs is induced by high glucose with increased expression of miR-328;overexpression of miR-328 induced EMT in HUVECs;miR-328 induced EMT is related with MEK1/2-ERK1/2 signaling pathway.

This study is to investigate the inhibitory effect of kaempferol on inflammatory response of lipopolysaccharide(LPS)-stimulated HMC-1 mast cells. The cytotoxicity of kaempferol to HMC-1 mast cells were analyzed by using MTT assay and then the administration concentrations of kaempferol were established. Histamine, IL-6, IL-8, IL-1β and TNF-α were measured using ELISA assay in activated HMC-1 mast cells after incubation with various concentrations of kaempferol (10, 20 and 40 µmol.L-1). Western blot was used to test the protein expression of p-IKKβ, IκBα, p-IκBα and nucleus NF-κB of LPS-induced HMC-1 mast cells after incubation with different concentrations of kaempferol. The optimal concentrations of kaempferol were defined as the range from 5 µmol.L-1 to 40 µmol.L-1. Kaempferol significantly decreased the release of histamine, IL-6, IL-8, IL-1β and TNF-α of activated HMC-1 mast cells (P<0.01). After incubation with kaempferol, the protein expression of p-IKKβ, p-IKBa and nucleus NF-κB (p65) markedly reduced in LPS-stimulated HMC-1 mast cells (P<0.01). Taken together, we concluded that kaempferol markedly inhibit mast cell-mediated inflammatory response. At the same time, kaempferol can inhibit the activation of IKKβ, block the phosphorylation of IκBα, prevent NF-KB entering into the nucleus, and then decrease the release of inflammatory mediators.
Cells, Cultured ; Histamine ; metabolism ; Humans ; I-kappa B Kinase ; metabolism ; I-kappa B Proteins ; metabolism ; Inflammation ; metabolism ; Interleukin-1beta ; metabolism ; Interleukin-6 ; metabolism ; Interleukin-8 ; metabolism ; Kaempferols ; pharmacology ; Lipopolysaccharides ; Mast Cells ; drug effects ; NF-KappaB Inhibitor alpha ; NF-kappa B ; metabolism ; Tumor Necrosis Factor-alpha ; metabolism

Objective:To evaluate the clinical advantage and disadvantage of anatomical landmark registration(ALR) and surface registration(SR) in computer-assisted endoscopic sinus surgery(CAESS).Method:Twenty-six patients were selected for the CAESS, the preparatory times and mean target registration errors (TRE) were recorded in order to compare the difference between them two, their convenience and their value were also analyzed.Result:CAESSs were successfully used in 26 cases without complications. The average preparation time of SR was(8.5±1.9)minutes, that of ALR was(6.5±1.7)minutes. In the SR group, the TRE of naso-labial angle was(1.43±0.26)mm, that of front end of middle turbinate was(1.92±0.47)mm, that of front end of inferior turbinate was (1.82±0.49)mm, and that of back end of inferior turbinate was (2.03±0.42)mm. Them in ALR group were (1.58±0.35)mm,(2.05±0.37)mm,(1.92±0.31)mm and (2.48±0.64)mm ,respectively.24 cases (92.2%) were not affected or were slightly affected by the navigation system. The value of navigation was affirmative in 22 cases (84.6%), and its value was mainly related to TRE.Conclusion:The accuracy of surface registration was superior to that of anatomical landmark registration, but the anatomical landmark registration was more convenient and need less preparation time. The value of navigation system is its accuracy, convenience and no disturbance to surgery. The navigation system is more valuable in the complex cases than that in the general case.

By summarizing the state of application of "syndrome differentiation through formula effect assessment", it was pointed out that several problems exist in this kind of study, mainly the irrational setting of experimental control group, over simplified pharmacodynamic indexes, and negligence of study on "correspondence between drug and disease", etc. The authors proposed accordingly the thinking methods and strategy in the study on "syndrome differentiation through formula effect assessment" should be setting control properly, taken "correspondence between disease and syndrome" as the key point, and to define clearly the criteria for evaluating the efficacy of formula as the premise.
Diagnosis, Differential ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Humans ; Male ; Medicine, Chinese Traditional ; methods ; Phytotherapy ; Research Design ; Syndrome

Aim To investigate the protective effect of Glucogon like pep tide-1 (GLP-1 )on H9C2 cardio-myocytes against AGEs-induced apoptosis and the po-tential molecular mechanisms.Methods H9 C2 car-diomyocytes cells cultured in vitro were divided into the following groups:normal control group ,1 0 0 mg · L-1 AGEs group,100 mg·L-1 AGEs+10 nmol·L-1 GLP-1 group,100 mg·L-1 AGEs+5 mmol·L-1 N-acetyl-cysteine (NAC)group.Cell viabillity rate was meas-ured by CCK-8 assay,ROS production was measured by DCFH-DA fluorescent probe;Cells in different groups were stained with Annexin V-FITC/PI and then apoptotic rate was detected by flow cytometry;Nucleus morphology was observed under fluorescence micro-scope after being incubated with Honchest 33258;Bax, Bcl-2 mRNA gene expression was measured using RT-PCR;Western blot was applied to assess the apoptotic components expression including Bax and Bcl-2.Re-sult Compared with control group,cell viability rate in AGEs group was decreased in a dose-dependent manner;cell apoptosis and ROS production in H9 C2 cells were remarkably increased in AGEs group.How-ever,compared with AGEs group,GLP-1 reduced ROS production and ameliorated cell apoptosis caused by AGEs;the expression of pro-apototic proteins Bax was decreased,the expression of anti-apoptotic proteins like Bcl-2 was increased. Conclusion GLP-1 protects H9 C2 cardiomyocytes against AGEs-induced apoptosis, which may be related to the reduction of the active oxy-gen (ROS).