This study assessed the clinical application of transvaginal three-dimensional ultrasound (3D TVUS) in the diagnosis of congenital uterine malformation. A retrospective study was performed on 62 patients with congenital uterine malformation confirmed hysteroscopically and/or laparoscopically. The patients were subjected to transvaginal two-dimensional ultrasound (2D TVUS) and 3D TVUS. The accuracy rate was compared between the two methods. The accuracy rate of 3D TVUS was (98.38%, 61/62), higher than that of 2D TVUS (80.65%, 50/62). 3D TVUS coronal plane imaging could demonstrate the internal shape of the endometrial cavity and the external contour of the uterine fundus. It allowed accurate measurement on the coronary plane, and could three-dimensionally show the image of cervical tube, thereby providing information for the diagnosis of some complex uterine malformation. 3D TVUS imaging can obtain comprehensive information of the uterus malformation, and it is superior to 2D TVUS for the diagnosis of congenital uterine malformations, especially complex uterine anomaly.

A series of novel sorafenib analogues were designed and synthesized. The cytotoxic activities of these compounds were tested in four tumor cell lines. Some of the compounds showed potent antiproliferative activity against the tested cell lines with IC50 = 4-20 micromol x L(-1). Some compounds demonstrated competitive antiproliferative activities to sorafenib against tested cancer cell lines. Among them, compound 7c demonstrated significant inhibitory activities on ACHN, HCT116 and MDA-MB-231 cell lines with IC50 values of 9.01, 4.97, 6.61 micromol x L(-1), respectively.
Antineoplastic Agents ; chemical synthesis ; chemistry ; pharmacology ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Humans ; Inhibitory Concentration 50 ; Molecular Structure ; Niacinamide ; analogs & derivatives ; chemical synthesis ; chemistry ; pharmacology ; Phenylurea Compounds ; chemical synthesis ; chemistry ; pharmacology ; Structure-Activity Relationship

The aim of this study is to evaluate anti-tumor activities and mechanism of a novel kinase inhibitor ZLJ213 which targeted Aurora A and vascular endothelial growth factor receptor (VEGFR) in vitro and in vivo against human colon cancer. Results showed that ZLJ213 inhibited cell proliferation and induced cell cycle arrest and apoptosis of HCT1 16 and SW48 cell lines. In HCT116-derived xenograft, ZLJ213 dosed at 100 mg · kg(-1) inhibited tumor growth by 73.24%. The IC50 of ZLJ213 on the expression of p-Aurora A was 0.258 µmol · L(-1) analyzed by ELISA. Under the concentration of 0.08 µmol · L(-1), ZLJ213 could inhibit the activities of Aurora A, Histone H3 and VEGFR of HCT116 and SW48 cell lines. Simultaneously, ZLJ213 induced activation of Caspase 3 and PARP cleavage. Above data suggested that ZLJ213 had the ability to inhibit cell proliferation and induce cell apoptosis both in vitro and in vivo in colon cancer, and down-regulate the expression of p-Aurora A and p-VEGFR. ZLJ213 might be a potential therapeutic agent against colon cancer.
Animals ; Apoptosis ; Aurora Kinase A ; antagonists & inhibitors ; Cell Cycle Checkpoints ; Cell Line, Tumor ; drug effects ; Cell Proliferation ; Colonic Neoplasms ; pathology ; Humans ; Protein Kinase Inhibitors ; pharmacology ; Receptors, Vascular Endothelial Growth Factor ; metabolism ; Xenograft Model Antitumor Assays

Objective To investigate the inhibitory effect of testosterone on oxidized low-density lipoproteins ( ox-LDL)-stimulated phenotypic transition and proliferation of vascular smooth muscle cells ( VSMCs) in vitro, and to explore its possible mechanisms. Methods Rat VSMCs cultured in vitro were divided into control group, ox-LDL group(50μg/mlox-LDL),fetalbovineserum(FBS)group(10% FBS),andtestosteronegroups(5×10-8 or5×10-7 mol/L testosterone plus 50μg/ml ox-LDL) . The effect of testosterone on ox-LDL-induced proliferation of VSMCs was explored by WST-1 assay. The cell cycle distribution was determined using flow cytometry. Western blotting was used todetecttheexpressionsofmitofusin2(Mfn2),phosphorylatedextracellularsignal-regulatedkinases1/2(p-ERK1/2) , proliferating cell nuclear antigen ( PCNA) ,α-smooth muscle actin (α-SMA) ,and osteopontin ( OPN) . Results Compared with control group, the proliferation of VSMCs was promoted by ox-LDL, the number of VSMCs decreased in G0/G1 phase and increased in S phase significantly, the expression levels of Mfn2 and α-SMA were significantly reduced, and the expression levels of p-ERK1/2, PCNA, and OPN were significantly raised in ox-LDL group. Compared with ox-LDL group, the proliferation of VSMCs was inhibited, the number of VSMCs increased in G0/G1 phase and decreased in S phase in two testosterone groups, along with the increased expressions of Mfn2 andα-SMA, and the descended expressions of p-ERK1/2, PCNA, and OPN. Conclusions Testosterone inhibits phenotypic transition and proliferation of VSMCs induced by ox-LDL in vitro, which may be related to the up-regulated expression of Mfn 2 and the suppression of ERK1/2 pathway.

Objective To evaluate the expression of RAR-? gene in cervical carcinoma cell lines SiHa,HeLa,C33A and Caski and to analyze the relation between their gene expression and the promoter methylation of RAR-? DNA.Methods The expression of mRNA and protein of RAR-? gene in the four cell lines were analyzed by RT-PCR,western blot and immunofluoreseence,respectively.Methylation specific PCR(MSP)was used to check whether there was methylation in the promoter of RAR-? gene.The demethylating agent 5-aza-2'-deoxycytidine(5-Aza-cdR)was used to treat methylated cell lines and the change of RAR-? gene methylation and RAR-? gene expression defects were observed.The cell proliferation was assayed with 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide method.Results The mRNA and protein expression levels of RAR-? in cell lines SiHa,HeLa,Caski and C33A were 0.25 ?0.08,0,0.60?0.19,3.12?0.92 and 0.23?0.07,0,0.14?0.05,0.68?0.21,respectively.The mRNA and protein expression of RAR-? in SiHa,HeLa and Caski cell lines were decreased or silenced, whereas its expression increased in C33A cell line.MSP method showed that there were RAR-? gene methylation in SiHa,HeLa and Caski cell lines,while there was no RAR-? gene methylation in C33A cell line.After treated with 5-Aza-cdR,the mRNA and protein expression levels of RAR-? in SiHa,HeLa, Caski and C33A cell lines were 1.82?0.59,2.13?0.62,1.67?0.43,2.95?0.89 and 0.69?0.21, 0.83?0.29,0.56?0.16,0.64?0.20 respectively.The mRNA and protein levels of RAR-? had a significant difference between before and after interference with 5-Aza-cdR in SiHa,Helm,and Caski cell lines(P0.05).The 5-Aza-cdR treatment could suppress cell proliferation.Conclusions The RAR-? gene expression defects play an important role in the carcinogenesis of cervical cancer.Aberrant methylation in promotor region of RAR-? gene may be an important mechanism for the loss of expression of RAR-? gene.

Permeability is a key factor in the bioavailability of oral drugs. Therefore, in the early stage of drug discovery, accurate and efficient evaluation of drug permeability is essential. The parallel artificial membrane permeability assay (PAMPA) with Caco-2 cells model was used by the industry as early evaluation methods. At present, the Ussing chamber rat model is also widely used. This review summarizes the human data for the in vivo single-pass perfusion technique (Loc-I-Gut) – the gold standard, and then focuses on the basic principles, experimental operation, and efficiency of the three in vitro methods, with correlation to the effective permeability coefficient (P_eff) and fractional absorbed (Fa) in man. We provide recommendations for the use of proper permeability methods at different stages in drug discovery and development.

ObjectiveTo investigate the effects of fluid percussion injury(FPI) on survival and differentiation of transplanted human embryonic neural stem cells (HNSCs) in rats. MethodsThe HNSCs were separated from the cerebral cortex of the 8-week-old fetal and were cultured in DMEM/F12 combinated with EGF, bFGF and LIF. The rat models of FPI were made with fluid percussion system. The HNSCs labeled with BrdU were transplanted into the injured zone 24 hours after brain injury, then the rats were killed at the 1st and 4th week post-transplanted stages, and the brain slices were stained with immunocytochemistry. The GFAP, MAP-2, and BrdU positive cells were investigated.ResultsThe transplanted HNSCs migrated to the whole brain, and differentiated into GFAP and MAP-2 positive cells. MAP-2 positive cells were observed at 1 week post-transplanted stage, on the contrary, more GFAP positive cells were discovered 4 weeks after transplantation. Part of the HNSCs migrated to the choroids plexus of the lateral ventricle and microvessels. ConclusionThe transplanted HNSCs survive in the injured zone, and differentiate into astrocytes gradually during the recovery. The host devours part of the HNSCs.

Female ; Humans ; Lymphoma, T-Cell ; diagnosis ; Middle Aged ; Multiple Myeloma ; diagnosis

The aim of the study is to investigate the effect of salvianolic acid B (SalB) on blood-brain barrier (BBB) in rats after cerebral ischemia-reperfusion, and to illustrate its possible mechanisms. Cerebral ischemia-reperfusion was induced by middle cerebral artery occlusion in rats. The break-down of BBB was indicated by extravasations of immunoglobulin (IgG) monitored with immunohistochemistry. The expression of MMP-9 and NOS2 in the brain was determined by immunohistochemistry, and the expression of p-p38 and p-ERK1/2 was detected by Western blotting. It was shown that on day 2 after ischemia-reperfusion the IgG accumulated around the vascular boundary zone, suggesting the break-down of BBB, and the expression of MMP-9 and NOS2 up-regulated at the same time. The result of Western blotting suggested that the expression of p-p38 and p-ERK1/2 increased. On day 7 after ischemia-reperfusion the. expression of MMP-9 and NOS2 was about the same level as day 2, the expression of p-p38 was higher than that on day 2 and the expression of p-ERK1/2 was slightly lower than that on day 2. SalB (1 and 10 mg x kg(-1)) significantly alleviated the extravasations of immunoglobulin induced by cerebral ischemia-reperfusion (P < 0.05). On day 2 and day 7 SalB attenuated the expression of MMP-9 and NOS2 (P < 0.05). SalB (10 mg x kg(-1)) reduced the expression of p-p38 and p-ERK1/2 apparently on day 2 and 7 after ischemia-reperfusion (P < 0.05). SalB (1 mg x kg(-1)) inhibited the expression of p-p38 on day 7 after ischemia-reperfusion (P < 0.05). The results indicate that SalB protects blood-brain barrier in rats after cerebral ischemia-reperfusion by inhibiting the MAPK pathway.
Animals ; Benzofurans ; isolation & purification ; pharmacology ; Blood-Brain Barrier ; drug effects ; metabolism ; Brain Ischemia ; etiology ; metabolism ; pathology ; Drugs, Chinese Herbal ; isolation & purification ; pharmacology ; Infarction, Middle Cerebral Artery ; complications ; MAP Kinase Kinase Kinase 1 ; metabolism ; MAP Kinase Signaling System ; drug effects ; Male ; Matrix Metalloproteinase 9 ; metabolism ; Nitric Oxide Synthase Type II ; metabolism ; Phosphorylation ; Plants, Medicinal ; chemistry ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Reperfusion Injury ; metabolism ; pathology ; Salvia miltiorrhiza ; chemistry ; p38 Mitogen-Activated Protein Kinases ; metabolism

Objective To explore the associations between vitamin D receptor ( VDR) Fok- Ⅰ and Apa- Ⅰ polymorphisms and myasthenia gravis (MG) in Chinese Han population.Methods Polymorphisms of VDR Fok- Ⅰ and Apa-Ⅰ were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method.The frequencies of genotypes and hyplotypes were compared among 286 normal controls and 267 MG patients in different subgroups classified by gender,age of onset,presence of thymoma,and Osserman classification sat maximal severity in the follow-up.The association between the genotypes and maximal severity of MG and short-term glucocorticoid treatment were also investigated.Results There were no significant differences in frequencies of genotypes and hyplotypes of both Fok-Ⅰ and Apa-Ⅰ between MG group and control group,and among subgroups of MG.The Fok- Ⅰ showed no statistical difference between the patients with better and less improvement after short-term treatment of glucocorticoid.The frequency of Apa-Ⅰ alleles in the patients with better improvement (55/186,29.6% ) significantly differed from the less improved group ( 7/48,14.6%,OR = 2.46,95% CI 1.04-10.43,x2 = 4.400,P = 0.036).The patients with the genotype A A/Aa were more likely to improve better after the treatment(48/93,51.6%) than in the worse group(7/24,29.2%,OR =2.59,95% CI 0.98-14.60,x2 =3.858,P= 0.049).Conclusions Alleles and genotypes of VDR-Fok- Ⅰ and Apa-Ⅰ were not found to be related with MG onset and severity.MG patients with VDR-Apa-A allele may have better improvement short-term treatment of glucocorticoid.