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.

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.

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.

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.

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.

Objective To investigate the metabolite changes in systemic lupus erythematosus (SLE) patients with and without neuropsychiatric symptoms using magnetic resonance spectroscopy (MRS) and explore the associations between image findings and clinical variables. Methods Twenty-two SLE patients with neuropsychiatric symptoms (NPSLE), twenty-one SLE patients without neuropsychiatric symptoms (non-NPSLE) and twenty healthy controls (HCs) underwent routine MRI scan and multivoxel magnetic reson-ance spectroscopy (MVS). The absolute metabolite concentrations were measured bilaterally in the posterior cingulate gyrus (PCG), dorsal thalamus (DT), lentiform nucleus (LN) and posterior paratrigonal white matter (PWM) using LCModel and SAGE software. The relationships between metabolite con-centrations and cognitive function scores were analyzed by Spearman rank correlation. Single-factor Chi-square analysis and t-test were used for analysis. Results ① Compared to control subjects, NPSLE patients had significantly lower N-acetylaspartate (NAA) values in bilateral PCG and DT, with the mean differences of -1.504 [95% confidence interval ( CI) (-2.335, -0.672), P=0.001], -1.460 [95%CI (-2.349, -0.570), P=0.002], -1.259 [95%CI (-1.894, -0.625), P=0.000] and -1.022[95%CI (-1.688, -0.356), P=0.003] for RPCG, LPCG, RDT and LDT, respectively. The concentration of total creatinine were observed to decline in RPCG and RDT, with the mean differences of-1.094 [95%CI (-1.845, -0.342), P=0.003], -0.955 [95%CI (-1.630, -0.280), P=0.006], -1.259 [95%CI (-1.894,-0.625), P=0.006] respectively. Glutamine and glutamate-values decreased significantly in RDT [mean difference=-2.586, 95%CI (-4.139, -1.033), P=0.002]. ② Compared to non-NPSLE patients, NPSLE patients had a lower NAA level in LPCG [mean difference=-1.256, 95%CI (-2.146, -0.367), P=0.006]. Positive correlations between mini-mental state examination scores [RPCG: rs=0.312, P<0.05; LPCG: rs=0.355, P<0.01], Montreal cognitive assessment scores (RPCG: rs=0.362, P<0.01; LPCG: rs=0.285, P<0.05) and NAA values in bilateral PCG were detected. Conclusion Both NPSLE and non-NPSLE patients may have metabolite dysfun-ctions in different brain regions. The cognitive disorder in SLE patients may be interpreted by neuronic damage of PCG.

The purpose of this study is to explore the feasibility of wheat germ agglutinin (WGA) modified liposome as a vehicle for ophthalmic administration. Liposome loaded with 5-carboxyfluorescein (FAM) was prepared by lipid film hydration method. WGA was thiolated and then conjugated to the surface of the liposome via polyethylene glycol linker to constitute the WGA-modified and FAM-loaded liposome (WGA-LS/FAM). The amount of thiol groups on each WGA molecule was determined, and the bioactivity of WGA was estimated after it was modified to the surface of liposome. The physical and chemical features of the WGA-modified liposome were characterized and the ocular bioadhesive performance was evaluated in rats. The result showed that each thiolated WGA molecule was conjugated with 1.32 thiol groups. WGA-LS/FAM had a mean size of (97.40 +/- 1.39) nm, with a polydispersity index of 0.23 +/- 0.01. The entrapment efficacy of FAM was about (2.95 +/- 0.21)%, and only 4% of FAM leaked out of the liposome in 24 h. Erythrocyte agglutination test indicated that after modification WGA preserved the binding activity to glycoprotein. The in vivo ocular elimination of WGA-LS/FAM fitted first-order kinetics, and the elimination rate was significantly slower than that of the unmodified liposome, demonstrating WGA-modified liposome is bioadhesive and suitable for ophthalmic administration.

To investigate the effects of cembrane-type diterpenes extracted from Sinularia flexibilis on the proliferation of PC12 cells and their protective effects on PC12 cells exposed to glutamate.

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.