Vascular endothelial growth factor receptors ( VEGFR ) belong to the receptor-type tyrosine kinase ( RTK ) super family and play important roles in tumor angiogenesis.Abnormal activation of VEGFR results in several disorders including cancer.VEGFR-2 is the major signal transducer for angiogenesis, and therefore, it becomes a good target for the inhibition of tumor development and metastasis.Nowadays, the VEGFR-based antiangiogenic therapy becomes one of the most powerful clinical strategies for cancer treatment.In this review, small molecular VEGFR-2 inhibitors are classified according to their structural features, their biological activities and current statue are briefly introduced.

Each WHO CC forms part of an inter-institutional collaborative network set up by WHO in support of its pro-gramme at the country,inter-country,regional,interregional and global levels.WHO Collaborating Centre for Diagnostics and Laboratory Support provide quality assurance programs for diagnostic technologies and diagnostic products on infectious disease for WHO and other international organization and act as a source of technical information for WHO,staff of national regulatory authorities and manufacturers.To promote the development of global health.It is very important for our country to establish the cooperation center of this function,to enhance the ability of our country’s in vitro diagnostic products in-spection,and to promote the development of the in vitro diagnostics industry.

Objective To develop a new system of computer-aided design(CAD) for individual metacarpophalangeal joint prosthesis based on rapid prototyping technique. Methods A hand of cadaver was scanned with PLUS-4 spiral computed tomography (CT).Then the transaxial 2D image data of digitus metacarpophalangeal joint were reconstructed into 3D digitized contour data by 3DMSR that was designed by ourselves. Then,the intramedullary stem was designed in software of Surface 9.0. Results The 3D contour image of metacarpophalangeal joint presented was reconstructed by 3DMSR and edited by Surface 9.0 easily for CAD of individual metacarpophalangeal joint.The intramedullary cavity was like choanoid. The intramedullary stem longitude of articular head and fossa were 47.31 and 35.20 mm.The intramedullary stem fit cavity.The model fit anatomical shape. Conclusion The 3D contour image of metacarpophalangeal joint can be obtained by spiral CT scanning,and the digitized data can be applied directly to CAD of individual artificial joint and subsequently rapid prototyping fabricating.In addition,the reconstruction method is simple and can be applied widely to clinical implant fabricating practice of orthopaedics.

Objective To develop an efficient recombinant expression system of alanine aminotransferase ( ALT ) in order to build the foundation for the preparation of feedstock related ALT reference materials.Methods A new human ALT gene was synthesized by optimizing the codons of the nucleic acid sequence encoding human ALT using bioinformatic tools, and then it was cloned into pRSF-Duet expression vector.The recombinant plasmid pRSF-Duet-ALT was transformed into E.coli BL21 and the target protein expression was induced by 2 mmol/L isopropyl β-D-1-thiogalactopyranoside ( IPTG ) .The expression condition for soluble protein was optimized by changing the inducer concentration, shaking speed and induction temperature. The soluble protein was purified by nickel ion affinity chromatography and dextran molecular sieve chromatography, and identified by sodium dodecyl sulfate-polyacrylamide gelelectrophoresis( SDS-PAGE) and Western blot analysis.The activity and stability of recombinant proteins in serum matrix under different storage conditions were detected.Results The usage frequency in E.coli of ALT codons was more than 10%after codon optimization.The expressions of soluble proteins were increased by optimizing the induced expression conditions, including a final concentration of 2 mmol/L of IPTG, and continued incubation with shaking at 150 rpm for 8 h at 25℃.The purified protein was identified as ALT by SDS-PAGE and Western blot with ALT activities of up to 80 000 U/L.Recombinant ALT could be stable for 2-8 d at 2-8 ℃or 25 ℃with a relative standard deviation of less than 5%.Conclusions An efficient recombinant expression system of ALT was developed successfully by codons optimization.The obtained recombinant protein could achieve the requirements of reference material feedstock.

Background and purpose:The most clearly recognized benefit of neoadjuvant chemotherapy (NAC) is that it can increase the proportion of patients who can be treated with breast-conserving therapy (BCT). However, the shrinkage modes of the primary breast tumor after NAC have been conifrmed as a predictor of BCT rate and prognosis. This study is to evaluate the accuracy of MRI predicting the shrinkage mode of the primary breast tumor after NAC with three-dimensional reconstruction technique.Methods:Sixty-one women with pathologically proven solitary invasive ductal carcinoma (ⅡA-ⅢC) were recruited. Breast specimens were prepared with PMSS, and residual tumors were microscopically outlined, scanned and registered by PHOTOSHOP software. The 3D model of residual tumors was reconstructed with 3D-DOCTOR software based on pathology and MRI imaging characteristics to evaluate the shrinkage mode. We devided the pathological shrinkage modes into surgical pCR (no residual tumors), solitary lesions without surrounding lesions, multinodular lesions, solitary lesions with adjacent spotty lesions and diffuse lesions. Further, the clinical-pathological shrinkage modes were divided into 2 categories: distinct shrinkage mode (DSM, the longest diameter of the pathological residual tumors was less than 50% and ≤2 cm in comparison with the primary tumor before NAC) and non-distinct shrinkage mode (NDSM, the longest diameter of the pathological residual tumors was more than 50% and/or >2 cm in comparison with the primary tumor before NAC).Results:The surgical pCR, solitary lesions without surrounding lesions, multinodular lesions, solitary lesions with adjacent spotty lesions and diffuse lesions were observed in 23, 17, 5, 9, 7 and 18, 3, 13, 20, 7 patients by MRI and pathology, respectively (P=0.001). The accuracy, sensitivity and speciifcity of MRI for predicting pathological shrinkage modes were 86.2%, 65.6% and 91.4%, respectively. The DSM was observed in 36 (59.0%) patients by pathology, and 38 (62.3%) patients by MRI. Two methods had a high consistency in clinical-pathological shrinkage modes (κ=0.863,P=0.000). The accuracy, sensitivity and speciifcity of MRI for predicting clinical-pathological shrinkage modes were 91.0%, 64.0% and 94.8%, respectively. There was not a statistic difference in prediction between DSM and NDSM by MRI (P>0.05). Receiver operating characteristic (ROC) curve analysis showed an AUC of 0.928 (P=0.000) for MRI to predict the clinical-pathological shrinkage mode.Conclusion:Three-dimensional MRI reconstruction after NAC could simulate and predict spatial location of residual tumors, and can be helpful in selecting patients who received BCT after NAC with tumor downstaging.

Objective To study the relationship between IGF-1, IGFBP-3 and prostatic volume (PV) by examining the levels of insulin and insulin-like growth fator-1 (IGF-1) and insulin-like growth factor binding protein-3 ( IGFBP-3 ) and other indicators in patients with impaired glucose regulation and benign prostate hypertrophy. Methods According to 75 g oral glucose tolerance test (OGTT) results, 109 BPH patients aged over 50 years were divided into three groups: normal glucose tolerance (NGT) group (n = 56), impaired fasting glucose (IFG) group (n = 14), impaired glucose tolerance (IGT group, n = 39). The biochemical indicators and postatic hyperplasia related factors and IGF-1, GFBP-3 were measured. Results There were no statistical differences between the three groups in terms of blood lipids, homocysteine, urinary inhibition C, fasting insulin (FINS), glycosylated hemoglobin, IGF-1 and IGFBP-3 (P > 0.05). There were no significant differences between the groups in terms of PV, prostate specific antigen, the quality of life score and the international prostate symptom score (P > 0.05). Fasting plasma glucose and insulin resistance index (HOMA IR) were higher in IFG group than NGT group (P′ < 0.017) and IGT group (P′ < 0.017). 2-hour plasma glucose and 2-hour insulin were higher in IGT group than NGT group (P′ < 0.017) and IFG group (P′ < 0.017). PV was positively correlated with FINS but not correlated with IGF-1, IGFBP- 3 by multiple multiple step wise regression analysis. Conclusion Oyperinsulinemia is a risk factor in the development of BPH with IGR, and IGF-1 and IGFBP-3 are not associated with BPH risk. Further investigation is needed to elucidate the role of the IGF-1 and IGFBP-3 in BPH.

Objective To explore the effect and safety of enhanced recovery after surgery (ERAS) in the surgical treatment of common bile duct stones.Methods According to random number table,48 patients with common bile duct stones were randomly divided into the ERAS group and the control group.The patients of the control group received the traditional perioperative management and laparotomy exploration of common bile duct.The patients of the ERAS group received the ERAS perioperative management and laparoscopic exploration of common bile duct.The preoperative and postoperative level of C reactive protein (CRP),time to out-of-bed activity,time to food taking,time to anal exsufflation,postoperative hospital stay,hospitalization cost and postoperative complications between the two groups were compared.Results Compared with the control group,the ERAS group had lower levels of CRP on the postoperative 1 day and 3 days[d1:(102.6±13.5) mg/L vs.(81.3±17.3)mg/L;d3:(71.8±15.3)mg/L vs.(41.2±11.2)mg/L,t=2.553,3.287,all P<0.05],had shorter time to out-of-bed activity[(3.2±1.8)d vs.(0.9±0.4)d],time to food taking[(4.3±1.9)d vs.(1.8±1.2)d] and time to anal exsufflation[(2.5±0.7)d vs.(1.2±0.3)d],and had shorter operative hospital stay[(7.3±3.2)d vs.(3.8±1.4)d]and less hospitalization cost[(7 200±800)RMB vs.(5 900±700)RMB] (t=5.561,4.319,3.765,2.351,1.671,all P<0.05).The incidence rate of postoperative complications of the ERAS group decreased markedly (61.91% vs.18.52%,x2=25.82,P<0.05).Conclusion ERAS management in the surgical treatment of common bile duct stones is safe and effective,which can enhance the recovery of the patients.

Objective To investigate the effects of mTOR/S6K1 signaling pathway on the development of insulin resistantce. Methods 20 male C57BL/6 mice were divided into normal diet group (NC) and high fat diet group (HF).HF mice were fed with high fat diet for 14 weeks and insulin resistance was confirmed in all mice. We observed the morphology of pancreatic islet by HE staining. Serum insulin concentration was also evaluated by ELISA. Northern blot, Western blot and immunofluorescence were performed to detect mTOR and S6K1 mRNA and protein expression in skeletal muscle. Results As compared with NC group,HF group showed that the body weight and fasting serum insulin level were increased by 21.99%(P＜0.05) and 181.82%(P＜0.01) respectively;the area of pancreatic islet was significantly increased;glucose tolerance was impaired;expressions of mTOR mRNA (125.61±10.43 vs 100.00, P＜0.05) and protein (137.41±7.86 vs 100.00, P＜0.01) were significantly increased. And we also found an significant increase in total S6K1 mRNA (154.98±16.26 vs 100.00, P＜0.01) and protein (137.36±3.08 vs 100.00,P＜0.01) as well as pS6K1 protein (390.15±69.62 vs 50.59±16.65,P＜0.01)expression in HF group as compared with NC group.Conclusions mTOR/S6K1 signaling pathway plays an important role in the development of higt fat diet induced insulin resistance.

This paper briefly introduces the working procedure of in vitro diagnostic products (IVD) industrial standards, and elaborates the importance of professional standards for production and supervision. Based on the analysis of working progress during the past 10 years, some problems and countermeasures on project setting, participation, standard material, personnel training, work cycle are put forward, which are helpful for the future development of the IVD.
Diagnostic Techniques and Procedures ; standards ; Humans ; Reference Standards

Objective:This study was conducted to evaluate the roles of internal mammary sentinel lymph node biopsy (IM-SL-NB) in the treatment of breast cancer patients with clinically positive axillary lymph nodes. Methods:This study is a one-armed clini-cal research conducted from June 2013 to October 2014. A total of 64 breast cancer patients from Shandong Cancer Hospital with clini-cally positive axillary lymph nodes were enrolled in the study. All patients underwent axillary lymph node dissection. Meanwhile, IM-SLNB was performed in all patients using the new injection method of radiotracer. Results:Among the 64 enrolled patients, the visual-ization rate of internal mammary lymph node was 59.4%(38/64). For the 38 patients who were subjected to visualization of the internal mammary node, the detection rate was 100%(38/38), and the incidence of complications was 7.9%(3/38). The metastasis rate of inter-nal mammary lymph node was 21.1%(8/38). Patients with upper inner quadrant tumors and metastasis of more axillary lymph nodes had a significantly higher chance of developing sentinel lymph node metastasis (P<0.001 and P=0.017, respectively) than the other pa-tients. The clinical benefit rate of the above mentioned treatment was 59.4%. Among the patients, 12.5%(8/64) received extra internal mammary radiotherapy, whereas 46.9%(30/64) patients avoided the unnecessary internal mammary radiotherapy. Conclusion:IM-SL-NB should be performed in breast cancer patients with clinically positive axillary lymph nodes because IM-SLNB could provide the ac-curate indication of radiation to the internal mammary area, especially for the patients with upper inner quadrant tumors and those with a suspiciously high level of axillary lymph node metastasis.