AIM　To investigate the transdermal delivery effects of cyclosporine A solubilized in mixed micelles composed of phospholipid and different surfactants. METHODS　When applied onto the excised abdominal skin of the mice occlusively, the enhancing effects of various mixed micelles on the penetration of cyclosporin A were assessed by an in vitro permeation technique. In vivo study was carried out by topical application of sodium cholate-phospholipid mixed micelles onto the mice skin and drug blood concentration was detected. RESULTS　In vitro, mixed micelles containing different surfactants displayed distinct permeability and corresponded to the following order: sodium cholate > sodium deoxycholate > Trition X-100 > Tween-20. In vivo, peak drug concentration was detected at 5 h and after that the concentration fell down slowly. CONCLUSION　Mixed micelles were shown to be efficient carrier for the transdermal delivery of the lipophilic polypeptide when kept in solution during the application process.

Objective:To investigate the effects of CCR3 on Muc5ac in the airway of asthmatic mice.Methods: Fifty clean BALB/c mice were randomly divided into control group,asthmatic group,dexamethasone treatment group,SB328437 treatment group, vehicle-control group.Total cells and differential inflammatory cells were counted in BALF, the levels of IL-4 and TNF-αwere determined by ELISA,lung tissue HE staining the expressions of Mucin5ac(Muc5ac) and CCR3 in lung tissue were detected by immu-neohistochemical staining and RT-PCR.Results:The total cells,eosinophil,monocytes and lymphocyte cells in BALF,the levels of IL-4,TNF-αin BALF ,the goblet cell of airway wall,the expression of Muc5ac and CCR3 positive staining IOD in the airway and the expression of Muc5ac and CCR3 mRNA lung tissue obviously decreased in SB328437 treatment group and DEX treatment group which compared with asthmatic mice model group ( P<0.05 ) .Conclusion: SB328437 can inhibit the expression of CCR3 in pulmonary tissue,furtherly inhibit the expression and secretion of Muc5ac and control the airway inflammation.

For effective inhalable dry-powder drug delivery, tetrandrine-PLGA (polylactic-co-glycolic acid) nanocomposite particles have been developed to overcome the disadvantages of nanoparticles and microparticles. The primary nanoparticles were prepared by using premix membrane emulsification method. To prepare second particles, they were spray dried. The final particles were characterized by scanning electron microscopy (SEM), dry laser particle size analysis, high performance liquid chromatography (HPLC), X-ray diffraction (XRD), differential scanning calorimetry (DSC), infrared analysis (IR) and confocal laser scanning microscope (CLSM). The average size of the primary particles was (337.5 ± 6.2) nm, while that second particles was (3.675 ± 0.16) μm which can be decomposed into primary nanoparticles in water. And the second particles were solid sphere-like with the drug dispersed as armorphous form in them. It is a reference for components delivery to lung in a new form.

An ordered mesoporous silica ( OMS ) was synthesized through hydrothermal process. The synthesized material was characterized by different techniques such as X-ray diffraction, nitrogen adsorption-desorption and transmission electron microscope. The electrochemical characteristics of the OMS modified carbon paste electrode ( OMS/CPE ) were investigated by using cyclic voltammetry and electrochemical impedance spectroscopy. Compared with bare carbon paste electrode ( CPE ) , the OMS/CPE exhibited a larger electrode surface and a faster electron-transfer rate. Electrochemical behaviors and kinetic properties of L-tryptophan ( L-Trp) at the OMS/CPE in the presence of sodium dodecylsulphate ( SDS) were studied. The results showed that the voltammetric response of L-Trp at OMS/CPE was improved due to the synergistic effect of OMS and SDS. The electrochemical oxidation of L-Trp at OMS/CPE in the presence of SDS was an irreversible process involved two electrons and two protons, and the electrode process was controlled by the adsorption step. Some parameters such as SDS concentration, accumulation time, accumulation potential and pH were optimized. Under optimal conditions, the oxidation peak current was linearly proportional to L-Trp concentration in the range of 8. 0×10-8 to 4. 0×10-6 mol/L, with a detection limit of 7. 0×10-8 mol/L (S/N=3 ) . The proposed method was applied for the determination of L-Trp in oral liquid with the recoveries of 99 . 6%-102 . 6%.

Aims To study the effects of diterpenoid pekinenal of Euphorbia pekinensis Rupr. on cell prolif-eration, cell cycle phase and apoptosis of hepatoma SMMC-7721 cells and to probe into its anti-cancer mechanisms. Methods MTT assay was used to inves-tigate the effect of pekinenal on proliferation of SMMC-7721 cells; TUNEL method, Annexin V/PI staining and electron microscopy were employed to observe the cell apoptosis; Flow cytometry was applied to analyze the distribution of cell cycle. Results Proliferation of SMMC-7721 cells was markedly inhibited by pekinenal in a dose-dependent manner; Annexin V/PI staining showed that with the increase of pekinenal concentra-tion, apoptotic rate of SMMC-7721 cells increased sig-nificantly, compared with control group, the difference has significant statistical significance ( P < 0. 01 ) . TUNEL method test results showed that different con-centrations of pekinenal in SMMC-7721 cells could in-duce liver cancer cell apoptotic and apoptotic index ( AI) increased significantly ( P <0. 01 ) with the in-crease of drug concentration. Compared with control group, electron microscope found that after the treat-ment, hepatocyte mitochondrial swelling, endoplasmic reticulum expansion, cytoplasm inclusion body forma-tion, part of the nucleus apoptosis, and the more obvi-ous apoptosis appeared with the increase of drug con-centration. Flow cytometry analysis showed that differ-ent concentrations of pekinenal could all make the cell block in S phase. Conclusion Pekinenal has an obvi-ously inhibitory effect on the human liver cancer cells, and there is significant concentration dependence; Pe-kinenal probably inhibits cancer cell DNA synthesis for the human liver cell cycle arrest in S phase and inhibits the proliferation . It plays a role in liver cancer inhibi-tion by inducing liver cancer cells apoptosis, etc.

OBJECTIVE: To analyze the prenatal diagnosis procedure for a 45,X male fetus. METHODS: A 31-year-old women underwent amniocentesis due to a moderate risk of trisomy 21. The fetal cells were subjected to chromosomal karyotyping, BACs-on-Beads (BoBs) assay, chromosomal microarray analysis and fluorescence in situ hybridization. RESULTS: Combined analyses revealed that the whole of Yp has translocated to 21p, which yielded a fetal karyotype of 45,X,dic(Y;21)(q11;p11).ishdic(Y;21)(SRY+,CEPY+;CEP21+). CONCLUSION BoBs and modified N-banding method are helpful for the diagnosis of 45,X male fetus with Yp translocation.

OBJECTIVE: To explore the value of BACs-on-Beads (BoBs) for the practice of prenatal diagnosis. METHODS: The results of chromosomal karyotyping and BoBs of 1773 prenatal samples were compared. Microdeletions and microduplications detected by BoBs were subjected to chromosome microarray analysis (CMA) with informed consent from patients. RESULTS: BoBs has detected 46 cases of common aneuploidies involving chromosomes 13, 18, and 21, and 16 cases involving X and Y chromosomes. For 4 fetuses with normal results by BoBs, karyotyping analysis of amniotic fluid sample suggested low percentage mosaicisms (< 20%). BoBs has detected none of the 9 common microdeletions, but 14 male fetuses with Xp22 microdeletions and 5 with other microdeletions/microduplications. In 10 cases, the couples had chosen CMA verification, and the results were all consistent. CONCLUSION As a rapid diagnostic technique, BoBs has a high accuracy for common aneuploidies, and is capable of discovering certain chromosome microdeletions and microduplications. The difficulty lies in the inability to detect low proportion mosaicisms and the consultation following detection for male fetuses carrying Xp22 microdeletions.

Objective:The therapeutic effect of less polar ginsenosides on rats with rheumatoid arthritis was studied, and the metabolic pathway that produce anti-inflammatory effect of less polar ginsenosides was identified.Methods:Rats were randomly divided into the control group, the model group, methotrexate treatment group, and high dose, medium dose, and low dose less polar ginsenosides groups. After 30 days of oral administration, less polar ginsenosides reduced the disease activity significantly in rats with rheumatoid arthritis. Blood and ankle synovial tissue metabolisms were measured by ultra performance liquid chromatography (UPLC) tandem mass spectrometry (MS) to explore the mechanism of less polar ginsenosides.The resulting data were subjected to principal component analysis and orthogonal partial least squares discriminant analysis(OPLS-DA).Results:Compared with the model group, erythrocyte sedimentation rate and RF decreased significantly in the high dose of less polar ginsenosides ( P<0.01). Metabolomics showed that R2X and R2Y of serum OPLS-DA were 0.626 and 0.904 respectively. The R2X and R2Y of synovial OPLS-DA were 0.429 and 0.689 respectively. Major differential metabolites were identified in the model group of rats, including arachidonic acid, valine, linoleic acid, and guanine nucleoside, etc. The main differential metabolites were identified in rats in the high dose group of less polar ginsenosides, including linoleic acid, betaine, eicosapentaenoic acid, alanine, methionine sulfoxide, isoleucine, etc. Conclusion:The metabolic spectrum has shown that inflammation is associated with linoleic acid metabolism, valine, leucine and isoleucine degradation, arachidonic acid metabolism. Less polar ginsenosides regulatethe linolenic acid metabolism, methionine metabolism and glucose alanine cycle.

We report a case of cushing's syndrome caused by ectopic adreocortical adenoma. The patient is a 37 years old woman, she was admitted to our hospital for " 2 years history of hypertension and weakness in both lower extremities for 2 months". Physical examination revealed: blood pressure 160/116 mmHg(1 mmHg＝0.133 kPa), body mass index 27.47 kg/m2, moon-face, increased fat in the neck and back, purple marks on abdominal skin, withⅡdegree edema of both lower extremities. Laboratory examination revealed that serum cortisol levels were elevated, loss of normal circadian rhythm, and serum adrenocorticotropic hormone (ACTH) was suppressed, the level of cortisol could not be suppressed in low dose desamethasone suppression test. Adrenal computed tomography ( CT) revealed a nodule in the right retroperitoneum, compression of the renal hilum, no bilateral adrenal adenoma and hyperplasia were found. This patient was diagnosed as corticotropin-independent Cushing's syndrome unequivocally. The clinical symptoms were relieved after successful laparoscopic retroperitoneum resection of the nodule. Pathological exam confirmed adrenocortical adenoma in ectopic adrenal tissue. Thus, we should consider the ectopic corticosteroid-secreting tumor in the context of corticotropin-independent Cushing's syndrome, especially when the imaging studies of adrenal revealed bilateral adrenal glands were normal or atrophic, which helped to make an appropriate strategy treatment.

Objective:To develop a self-made plasma quality control material for non-invasive prenatal testing (NIPT) and evaluate its performance.Methods:139 NIPT-negative maternal plasmas stored in the genetic department of Shaoxing maternal and child health hospital from January 1, 2019 to June 30, 2021 were divided into male groups (19 cases) and female groups (120 cases) according to the neonatal gender. 9360 cases from September 2020 to September 2021 were enrolled as clinical validation cases.First step, 200 μl plasma from a 47 years-old non-pregnant healthy women was used as a matrix. Different amounts (0.1, 0.2, 0.5, 2.5, and 5 μl) of positive DNA from fetal chromosome aneuploidy (T21, T18, T13) detection kit were added. The appropriate volume of positive DNA was 0.5 μl according to the test results. Second step,Plasma in male and female group was treated as matrix. 0.5 μl positive DNA was added per 205 μl. Plasma matrix from female group showed good repeatability and the sensitivity was 100%.Third step, evaluate the self-made plasma quality control material, including storage stability, matrix uniformity and repeatability, and the effect of different batch numbers of positive DNA, by calculating Z score and the CV of fetal DNA concentration (FF).Results:Plasma matrix from female group showed good repeatability and the sensitivity was 100%, while the sensitivity of male group was only 84%. The CV of FF in female matrix was 3.9% in the repetitive experiments. After adding 0.5 μl positive DNA, the mean FF of self-made positive plasma quality control was 5.63%±0.42%, Z values>6, and the CV was 7% after storage of three months. Considering the concentration variation of positive DNA in different lots, 1 μl of positive DNA should be added when the FF of positive DNA is lower than 10%.Used in 9360 clinical cases from September 2020 to September 2021, all positive plasma quality control materials showed positive results, and the positive predictive value of trisomy 21 was 100%.Conclusions:The NIPT self-made positive plasma quality control material has been successfully developed in this study. The preliminary experimental results show that it has good repeatability and stability, which is suitable for clinical application.