Vasculogenic mimicry (VM) is a term that describes a novel form of angiogenesis, channels of which are patterned networks of interconnected loops of periodic acid-Schiff (PAS)-positive extracellular matrix forming by highly aggressive tumor cells instead of endothelial cells. VM is closely correlated with the invasiveness, metastasis and prognosis of related tumors. However, traditional anti-vascular therapies aiming at endothelial cells have no remarkable effects on malignant tumor with VM. Therefore, VM should be an important factor to consider in design of anti-angiogenesis therapies of highly aggressive tumors and it is expected to become a potential target for tumor therapy. Some recent progresses of anti- vasculogenic mimicry therapy are reviewed in this article.

The occurrence rate of colorectal cancer is increasing. Metastasis and recurrence are the leading causes of death in colorec-tal cancer. Tumor cells in the circulation have the ability to proliferate or to migrate, thereby providing a reliable means for neoplasm staging and assessment of recurrence or metastasis, and evaluation of efficacy by detecting circulating tumor cells (CTC). Optimizing the development of detection technology will provide better support for clinical applications. This review mainly discusses CTC detec-tion and advances in colorectal cancer relapse or metastasis.

AIM:Nitroxyl ( HNO) increases myofilament Ca 2+responsiveness relative to increases in intracel-lular Ca2+in cardiac muscle.In this study, we further investigated this effect of HNO on trabecular muscles from phospho-lamban knockout ( PLB-KO) and wide-type ( WT ) mice using a novel HNO donor , 1-nitrosocyclohexyl acetate ( NCA ) . METHODS:Trabecular muscles were dissected from the right ventricles of the rat hearts and mounted between a force transducer and a motor arm.The muscles were superfused with K-H solution (pH 7.4) at room temperature.Fura-2 was loaded into the trabecular muscles via electrophoresis .The length of the sarcomere was set to 2.2~2.3μm.During stead-y-state activations, the maximal Ca2+-activated force and Ca2+required for 50% activation were measured.RESULTS:The intracellular Ca 2+transients and force of the PLB-KO muscles at baseline were higher than those of the WT muscles and exhibited a negative force-frequency relationship (FFR).NCA (2.5μmol/L) increased systolic force in both PLB-KO group and WT group at any given [Ca2+]o.However, there was more dramatic increase in the force development due to moderate increases in the intracellular Ca 2+transients in the WT muscles when external Ca 2+increased from 1.5 to 4.5 mmol/L under NCA.NCA did not affect the negative FFR in PLB-KO muscle.Steady-state force-Ca2+relations obtained from skinned muscles were not different between the 2 groups, while NCA increased Ca2+responsiveness in skinned mus-cles from both PLB-KO and WT mice.CONCLUSION:HNO increases force development in both PLB-KO and WT mus-cles as a result of increases in myofilament Ca 2+responsiveness .The increased intracellular Ca 2+transients are accompa-nied by greater force development in WT mice , suggesting that HNO improves Ca 2+activation and establishes HNO as a positive inotropic agent with novel mechanisms .

Objective To investigate the clinical features,karyotype,and the prenatal diagnosis for his sibling of a Chinese patient with rare ring chromosome 20 syndrome induced intractable epilepsy.Methods The clinical data of the patient diagnosed in Peking University People's Hospital were collected.The clinical manifestations,chromosome karyotype were summarized.Results The proband,a boy,started to show intermittent tonic seizures or atypical absence seizures and psychomotor retardation from the age of 11 months.Several anti-epilepsy drugs and globulin had been tried without effect.Common karyotype analysis and epilepsy-related genes analysis revealed no abnormality.However,abnormal karyotype 46,XY,r(20)(p13q13.3) in his peripheral blood lymphocytes was found by high resolution chromosome karyotype analysis with 550 G-banding,and the diagnosis of ring chromosome 20 syndrome,type Ⅱ was confirmed.The mother of the patient underwent amniocentesis at the midterm of the second pregnancy.The cultured amniocytes karyotypes were normal.The second child(a boy) of the family was 1 year old without epilepsy and the psychomotor development was normal.Conclusions Ring chromosome 20 syndrome is a rare human chromosome abnormality.The syndrome is associated with epileptic seizures,behavior disorders and mental retardation.Since karyotype testing is not a routine investigation for the patient with epilepsy,the diagnosis of ring chromosome 20 syndrome is usually delayed or misdiagnosed.The karyotype analysis should be considered for the etiological study of the patients with intractable epilepsy with unknown origin.

ObjectiveTo understand the distribution of interleukin(IL)-28B gene polymorphisms in human immunodeficiency virus (HIV)/hepatitis C virus (HCV) coinfected Han patients in Hubei Province.MethodsOne hundred Han patients with anti-HIV and anti-HCV double positive in Hubei Province were enrolled.HCV RNA level was detected by fluorescence quantitative polymerase chain reaction (PCR) and genotyping of IL-28B gene was pcrformed by sequencing.The data were analyzed by chi square test.ResultsThe proportion of IL-28B C/C genotype was 95.0 ％ in target population,arnong which 21.1％ (20/95) were HCV RNA negative.While there were no HCV RNA negative cases in C/T and T/T genotypes (0/5;x2 =1.043,P=0.588).ConclusionAmong HIV/HCV coinfccted Han patients in Hubei Province,the proportion of IL-28B C/C genotype is high.

Objective To explore the effect of dendritic cells (DC) primed by total RNA extracted from human colon cancer Lovo cell on specific cytotoxicity of cytokine-induced killer cells (CIK) in vitro.Methods Cord blood mononuclear cells extracted by Ficoll density gradient centrifuge were induced into CIK and DC cells separately, and their Immunophenotype was detected by Flow cytometer. Trizol harvested total RNA from colon cancer cell Lovo and the RNAs were loaded to DCs obtained from cord blood as tumor anti gens. Effectors were grouped accordingly as CIK cells co-cultured with DCs transfected with Lovo RNA, CIK cells co- cultured with unloaded DCs and CIK cells. Targets was Lovo cells. In vitro cytotoxicity of CHK cells was extured with DCs loaded with Lovo RNA(76.49%±4.21%), DC + CIK group was lower(53.84% ± 2.15%),and CIK cells group possessed the lowest cytotoxicity(32.20% ± 3.07%), showing statistic significance( P ＜0.05). Conclusion Extraction of total RNA from tumor cells is simple and easy for clinical implementation.Total RNAs acted as antigen to pulse DCs can strengthen the specific cytotoxicity of CIK cells, which will have good prospects for clinical application.

Objective To evaluated the efficacy of biomarker?guided concurrent chemoradiotherapy in unrescetable esophageal squamous cell carcinoma patients. Methods 54 cases of unrescetable esophageal squamous cell carcinoma were enrolled in the prospective non?randomized clinical study and divided into study group and control group. All cases were treated with concurrent chemoraditherapy. Intensity?modulated radiation therapy was used with a dose of 60?66 Gy. Chemotherapy was perfromed on day 1 and d29. In the study group the selection of the chemotherapy drug was based on the excision repair cross?complementation 1 ( ERCC1) ,thymidylate synthetase ( TYMS) ,ribonucleotide reductase M1( RRM1) ,and theβ?tubulin isotypeⅢ( TUBB3) mRNA expression levels. In the control group,the regiment for chemotherapy was Cisplatin plus Fluorouracil. The objective response rate and overall survival ( OS ) were calculated using Kaplan?meier method and log?rank test was used for between?group comparison. The survival rate was calculated using Kaplan?Meier method and analyzed using log?rank method, other comparison was performed by χ2 test. Results The follow?up rate was 100% in the study group and 96% in the controll group. The objective response rate of the study group and the control group were 85% and 86 ( P=0. 483 ) , respectively. The median survival time ( MST) in the study group was 35. 5 months and that in the control group was 25. 8 months. The 1?,2?,and 3?year OS rates of the study group and the control group were 84%,68%,46% and 71%,59%,28% respectively (P=0. 047).No significant differences were observed in the incidence of side?effects in the two groups. Conclusions Selecting the chemotherapy drug according to biomarker,combined with radiation therapy,could improve survival.in unrescetable esophageal squamous cell carcinoma. The value needs further investigation.

This study was aimed to assess the effect of Shenfu injection on different circulation state. Using a microcirculation microscope system, we observed mice's auricle micro-artery diameter, density of capillary, blood velocity in different circulation state (i.e. normal state, epinephrine or endotoxin induced microcirculation disturbance state) after administering Shenfu injection into their caudal vein, and we compared the Shenfu group with Shenmai group and Dexamethasone group. The results showed that Shenfu injection causes the auricle microartery diameter to enlarge and the density of capillary and blood velocity to increase in different microcirculation state, and such effect is especially notable on the epinephrine induced microcirculation disturbance group and endotoxin induced microcirculation disturbance group; the effect of Shenfu injection is stronger than that of Shenmai injection and similar to Dexamethasone injection. In addition, Shenfu injection was shown to have remarkable effect on resisting the lowering of limb temperature when the mice are attacked by endotoxin.
Animals ; Blood Flow Velocity ; drug effects ; Drugs, Chinese Herbal ; administration & dosage ; pharmacology ; Ear ; blood supply ; Endotoxins ; toxicity ; Epinephrine ; toxicity ; Female ; Injections ; Male ; Mice ; Microcirculation ; drug effects ; physiology

Objective To explore the clinical and genetic features in the pedigree of Cb1X type X-linked methylmalonic aciduria. Methods Clinical data of one child with X-linked methylmalonic aciduria diagnosed by blood and urine analysis were analyzed retrospectively. Targeted next-generation sequencing has been performed to detect the mutation of methylmalonic aciduria-related genes. Results The boy started presenting with seizures and severe mental retardation at 2 months of age. At 5 months of age, he had the manifestations of seizures, severe mental retardation, increased methylmalonic acid in urinary, increased propionylcarnitine in blood and increased plasma homocysteine, and met the requirements for the diagnosis of methylmalonic aciduria complicated with hyperhomocysteinemia. No mutation was detected in his MMA-related autosomal genes. However, a hemizygote mutation c.344C?>?T (p.Ala115Val) was identiifed in exon 3 of HCFC1 in X chromosome, which conifrmed the CblX type methylmalonic aciduria. His parents were healthy. His elder brother also manifested severe psychomotor retardation with intractable epilepsy, and died at 6 months of age with unknown cause. His mother carried the same mutation and had slightly elevated urine methylmalonic acid and plasma total homocysteine. His father did not carry the mutation. Conclusion A pedigree of a rare Cb1X type X-linked methylmalonic acidemia is ifrstly diagnosed in China by the new generation sequencing technology.

Objective To screening optimized ultrasound (US)condition for MCF-7 cells and MCF-7/Tax cells,and to investigate the effect of dual-ligands nanoparticles (NPs ) combined with US on overcoming multidrug resistance (MDR).Methods To obtain optimized US condition,cell viability and cellular uptake of NPs treated with MCF-7 cells and MCF-7/Tax cells were detected under different ultrasonic parameters including ultrasound intensity,exposure duration and microbubble concentration. MTT assay was performed to observe the effect of NPs combined with US on cells.Results The optimal US conditions for MCF-7 cells was irradiation intensity 0.6 W/cm2 ,irradiation time 80 s,and the MBs concentration with volume ratio of microbubbles to medium was 1∶1 0;and for MCF-7/Tax cells,irradiation intensity 0.6 W/cm2 ,irradiation time 80 s,and the MBs concentration with volume ratio of microbubbles to medium was 1∶20.Compared with individual NPs,NPs assisted by US exhibited greater killing ability for MCF-7 (IC50 1 .43 ng/ml)and MCF-7/Tax cells (IC50<800 ng/ml).Conclusions US effect could enhance drug sensitivity of the dual-functionized NPs for MCF-7/Tax cells,indicating that US irradiation had potential assisted modality to reverse tumor MDR.