OBJECTIVE:To study the effects of paclitaxel combined with cisplatin on the proliferation,migration and invasion of thyroid cancer cells SW579 and its mechanism. METHODS:Cells were divided into blank control group,paclitaxel group (3μmol/L),cisplatin group(30 μmol/L),drug combination group(paclitaxel 3 μmol/L+cisplatin 30 μmol/L). 48 h after culture,the relative cell activity was measured by MTT assay. Cell cycle was detected by flow cytometry. Migration and invasion of cell was tested by Transwell assay. The expression of phosphatase and tensin homolog deleted on chromosome ten(PTEN),protein kinase B(AKT),Cyclin D1,p27,matrix metalloproteinase(MMP)-2 and MMP-9 were detected by Western blot. RESULTS:Compared with blank control group,relative cell activity of all treatment groups were decreased;paclitaxel or plus cisplatin also made cell cy-cle arrest in G1 phase,and migration and invasion ability of cell were decreased;the expression of PTEN and p27 remarkably in-creased,while the expression of Cyclin D1,MMP-2,MMP-9 and phosphorylation of AKT were obviously reduced,with statisti-cal significance (P<0.05). Compared with single drug group,the effect of drug combination group strengthened,with statistical significance in above indicators(P<0.05). CONCLUSIONS:The inhibition effect of paclitaxel combined with cisplatin on the pro-liferation,migration and invasion of thyroid cancer cells SW579 cell will be strengthened,by a mechanism of up-regulating the ex-pression of PTEN and p27,down-regulating the expression of Cyclin D1,MMP-2 and MMP-9,inhibiting phosphorylation of AKT.

The association rate constant and dissociation rate constant are important parameters of the drug-cyclodextrin supermolecule systems, which determine the dissociation of drugs from the complex and the further in vivo absorption of drugs. However, the current studies of drug-cyclodextrin interactions mostly focus on the thermodynamic parameter of equilibrium constants (K). In this paper, a method based on quantitative high performance affinity chromatography coupled with mass spectrometry was developed to determine the apparent dissociation rate constant (k(off,app)) of drug-cyclodextrin supermolecule systems. This method was employed to measure the k(off,app) of meloxicam and acetaminophen. Firstly, chromatographic peaks of drugs and non-retained solute (uracil) on β-cyclodextrin column at different flow rates were acquired, and the retention time and variance values were obtained via the fitting the peaks. Then, the plate heights of drugs (H(R)) and uracil (H(M,C)) were calculated. The plate height of theoretical non-retained solute (H(M,T)) was calculated based on the differences of diffusion coefficient and the stagnant mobile phase mass transfer between drugs and uracil. Finally, the k(off,app) was calculated from the slope of the regression equation between (H(R)-H(M,T)) and uk/(1+k)2, (0.13 ± 0.00) s(-1) and (4.83 ± 0.10) s(-1) for meloxicam and acetaminophen (control drug), respectively. In addition, the apparent association rate constant (k(on,app)) was also calculated through the product of K (12.53 L x mol(-1)) and k(off,app). In summary, it has been proved that the method established in our study was simple, efficiently fast and reproducible for investigation on the kinetics of drug-cyclodextrin interactions.

The release behavior of single pellet was investigated by LC/MS/MS method with tamsulosin hydrochloride (TSH) as the model drug of the research and then the pellets were divided into four groups according to the drug loading. Comparison of dissolution profiles of each group and capsule were performed using f1 and f2 factor methods to study the difference and similarity. The release profiles of single pellet, each group and capsule were analyzed using principle component analysis (PCA). The particle system was built through Matlab to get the target release profile. The result of this research demonstrated the release behavior of single pellet correlated well with the drug loading. While the dissolution profile of capsule as a reference, the similarity factor of dissolution profiles of the lower drug loading groups were 62.2, 67.1, 53.9, respectively and, 43.3 for highest drug loading group. The particle systems with different pellet distribution and same release profiles were built through release behavior of single pellet. It is of significance to investigate the release behavior of single pellets for studying the release regularity of multiple-unit drug delivery system.

Objective:To investigate the application value of spiral CT combined with a disintegrin and metalloproteinase 8 (ADAM8), neuron-specific enolase (NSE) and cytokeratin 19 fragment (CYFRA21-1) measurements in the clinical diagnosis of lung cancer.Methods:Fifty patients with lung cancer who received treatment in Shanxi Rongjun Hospital from February 2018 to December 2019 were included in the lung cancer group. Fifty patients with benign lung disease who concurrently received treatment in Shanxi Rongjun Hospital were included in the benign lung disease group. Fifty 50 healthy controls who concurrently received treatment in Shanxi Rongjun Hospital were included in the control group. Serum levels of ADAM8, NSE and CYFRA211 were compared among the three groups. Three groups received spiral CT scans. ADAM8-, NSE- and CYFRA211-positive detection rates were analyzed. The receiver operating characteristic (ROC) curve was used to analyze the efficacy of different methods in the diagnosis of lung cancer. Serum ADAM8, NSE and CYFRA211 levels in patients with lung cancer at different TNM stages were compared.Results:Serum levels of ADAM8, NSE and CYFRA211 in the lung cancer and benign lung disease groups were (381.69 ± 34.82) ng/L, (255.28 ± 30.48) ng/L, (16.87 ± 3.11) μg/L, (9.27 ± 2.11) μg/L,(13.54 ± 8.10) μg/L, (3.01 ± 1.34) μg/L, respectively, which were significantly higher than those in the control group [(225.83 ± 24.19) ng/L, (7.42 ± 2.35) μg/L, (1.78 ± 1.02) μg/L, t = 5.352, 25.994, 4.142, 17.142, 5.165, 10.186, all P < 0.05]. Serum levels of ADAM8, NSE and CYFRA211 in the lung cancer group were significantly higher than those in the benign lung disease group ( t = 19.316, 14.299, 9.069, all P < 0.05). The positive detection rate of lung cancer by spiral CT combined with ADAM8, NSE and CYFRA211 measurements was 92.00%, which was significantly higher than that by spiral CT combined with a single detection ( χ2 = 7.862, 9.000, 11.422, 9.000, all P < 0.05). The ROC curve analysis revealed that the area under the ROC curve, sensitivity and specificity of the combined method were 0.916, 0.920 and 0.900, respectively, which were significantly higher than those of spiral CT combined with a single detection. Serum ADAM8, NSE and CYFRA211 levels at TNM stages III-IV were (430.18 ± 36.43) ng/L, (20.05 ± 3.49) μg/L, (15.93 ± 8.22) μg/L, respectively, which were significantly higher than those at TNM stages I-II [(314.72 ± 30.85) ng/L, (12.49 ± 2.67) μg/L, (10.25 ± 6.35) μg/L, t = 11.777, 8.312, 2.644, all P < 0.05). Conclusion:Spiral CT combined with serum ADAM8, NSE and CYFRA211 levels can greatly increase the diagnostic sensitivity and specificity of lung cancer, which is worthy of clinical application.

Objective:To assess the changes of myocardial biomechanical parametres of left ventricle of the patients with non-Hodgkin lymphoma (NHL)after anthracycline (ANTH)treatment by using two dimension speckle tracking imaging (2D-STI),and to study the value of 2D-STI in evaluating and monitoring the early cardiac dysfunction of the NHL patients induced by ANTH treatment.Methods:A total of 37 hospital patients who were firstly diagnosed as NHL (ANTH chemotherapy group)and 20 healthy volunteers (normal control group)were selected.The global longitudinal strain (GLS),global radial strain (GRS),global circumferential strain (GCS) and left ventricle twist (LVtw)of the subjects in two groups were detected before chemotherapy and 1,2,3 weeks after chemotherapy with 2D-STI;the GLS×LVtw was calculated.Results:There were no significant differences in the general clinical parameters of the subjects between normal control group and ANTH chemotherapy group before chemotherapy (P >0.05);the values of GLS,GRS and GCS of the patients in ANTH chemotherapy group after ANTH chemotherapy were decreased than those in normal control group and before ANTH chemotherapy (P <0.05),and GLS had the most obvious change.The GLS, GRS, GCS and GLS × LVtw of the patients after 3 cycles of chemotherapy in ANTH chemotherapy group were decreased (P > 0.05 ). Four patients meet the diagnostic criteria of cardiac toxicity in the couse of chemotherapy.The sensitivity was 94%,the specificity was 66.7%,and the maximal Youden index was 0.667 when the △ GLS × LVtw =-64.53% ×°was used as the cut-off point in predicting the occurrence of myocardial toxicity.Conclusion:2D-STI can detect the early changes of biomechanical parameters of left ventricular myocardium with highly sensitive in predicting early myocardial toxicity and early cardiac dysfunction caused by ANTH chemotherapy.It may be an effective way to predict the early myocardial toxicity of ANTH chemotherapy in the future.

In an answer to the challenge of enzymatic instability and low oral bioavailability of proteins/peptides, a new type of drug-delivery vesicle has been developed. The preparation, based on sodium dodecyl sulfate (SDS) and β-cyclodextrin (β-CD) embedded in chitosan gel, was used to successfully deliver the model drug-insulin. The self-assembled SDS/β-CD vesicles were prepared and characterized by particle size, zeta potential, appearance, microscopic morphology and entrapment efficiency. In addition, both the interaction of insulin with vesicles and the stability of insulin loaded in vesicles in the presence of pepsin were investigated. The vesicles were crosslinked into thermo-sensitive chitosan/β-glycerol phosphate solution for an in-situ gel to enhance the dilution stability. The in vitro release characteristics of insulin from gels in media at different pH values were investigated. The insulin loaded vesicles-chitosan hydrogel (IVG) improved the dilution stability of the vesicles and provided pH-selective sustained release compared with insulin solution-chitosan hydrogel (ISG). In vitro, IVG exhibited slow release in acidic solution and relatively quick release in neutral solutions to provide drug efficacy. In simulated digestive fluid, IVG showed better sustained release and insulin protection properties compared with ISG. Thus IVG might improve the stability of insulin during its transport in vivo and contribute to the bioavailability and therapeutic effect of insulin.

syndrome is classified into five categories. Based on the syndrome differentiation of meridians and collaterals andtheories, Professorproposed the fire needling therapy at the lower-sea points for five types ofsyndromes. Professorstresses on the flexible application of fire needling therapy forsyndrome at the lower-sea points and innovated the unique five techniques of fire needling therapy, named lifting and threating needle of small amplitude at the lower-sea points, the stimulation along the relevant meri-dians before fire needling, detecting the sensitive sites by gentle pressing the relevant lower-sea points, combining the movement of affected upper limb or joint during fire needling, or combining with contralateral needling technique, and controlling the depth of fire needling based on the duration of sickness and depth of affected site. He pointed out that Shangjuxu (ST 37) is for skinsyndrome, Zusanli (ST 36) for musclesyndrome, Yanglingquan (GB 34) for tendonsyndrome, Weizhong (BL 40) for bonesyndrome and Xiajuxu (ST 39) for vesselsyndrome.

Tremendous efforts have been devoted to the enhancement of drug solubility using nanotechnologies, but few of them are capable to produce drug particles with sizes less than a few nanometers. This challenge has been addressed here by using biocompatible versatile -cyclodextrin (-CD) metal-organic framework (CD-MOF) large molecular cages in which azilsartan (AZL) was successfully confined producing clusters in the nanometer range. This strategy allowed to improve the bioavailability of AZL in Sprague-Dawley rats by 9.7-fold after loading into CD-MOF. The apparent solubility of AZL/CD-MOF was enhanced by 340-fold when compared to the pure drug. Based on molecular modeling, a dual molecular mechanism of nanoclusterization and complexation of AZL inside the CD-MOF cages was proposed, which was confirmed by small angle X-ray scattering (SAXS) and synchrotron radiation-Fourier transform infrared spectroscopy (SR-FTIR) techniques. In a typical cage-like unit of CD-MOF, three molecules of AZL were included by the -CD pairs, whilst other three AZL molecules formed a nanocluster inside the 1.7 nm sized cavity surrounded by six -CDs. This research demonstrates a dual molecular mechanism of complexation and nanoclusterization in CD-MOF leading to significant improvement in the bioavailability of insoluble drugs.

Cyclodextrin metal-organic framework (CD-MOF) as a highly porous supramolecular carrier could be one of the solutions to the insolubility of isosteviol (STV). The solubility of STV was lower than 20.00 ng/mL at pH 1.0 and pH 4.5, whilst its solubility increased to 20,074.30 ng/mL at pH 6.8 and 129.58 ng/mL in water with a significant pH-dependence. The

Nasal drug delivery efficiency is highly dependent on the position in which the drug is deposited in the nasal cavity. However, no reliable method is currently available to assess its impact on delivery performance. In this study, a biomimetic nasal model based on three-dimensional (3D) reconstruction and three-dimensional printing (3DP) technology was developed for visualizing the deposition of drug powders in the nasal cavity. The results showed significant differences in cavity area and volume and powder distribution in the anterior part of the biomimetic nasal model of Chinese males and females. The nasal cavity model was modified with dimethicone and validated to be suitable for the deposition test. The experimental device produced the most satisfactory results with five spray times. Furthermore, particle sizes and spray angles were found to significantly affect the experimental device's performance and alter drug distribution, respectively. Additionally, mometasone furoate (MF) nasal spray (NS) distribution patterns were investigated in a goat nasal cavity model and three male goat noses, confirming the in vitro and in vivo correlation. In conclusion, the developed human nasal structure biomimetic device has the potential to be a valuable tool for assessing nasal drug delivery system deposition and distribution.