Objective To evaluate magnetic resonance imaging (MRI) for breast-conserving surgery. Methods In this study, 52 cases of breast cancer eligible for breast-conserving surgery judged by traditional screening methods from May 2004 to December 2007 were inspected preoperatively with MRI in order to detect the cases of muhicentric breast cancer. At the same time, tumor size and invasive extent was measured accurately with enhanced magnetic resonance sequence combined with fat-suppression to determine the minimally extent of the surgical excision required. Results In the 52 cases of breast cancer patients, 3 cases of multicentric breast cancer and 49 cases of single breast cancer were diagnosed by MRI ,there were 3 cases with extensive intraductal carcinoma in the cases of single breast cancer. The primary negative margin rate was 93.6% (44/47) in the 47 cases with breast-conserving surgery. Conclusions MRI has thesuperiority to detect the muhicentric disease and the extensive intraductal carcinoma of breast cancer.Therefore MRI is useful in determining the indication and the extent of surgical excision of breast-conservingsurgery.

Objective To evaluate the application of totally implantable central venous access ports. Methods A retrospective a-nalysis of 217 cases was made on the application and complication of totally implantable central venous access ports from October 2003 to May 2008. Results Venous access ports, which were connected to central venous system via subclavian vein in 199 cases and jugularis interna vein in 17 cases, were implanted into subcutaneous of chest wall. The success rate of implantation was 99.6% (216/217). The ports worked well in 207 cases (95.8%), and 9 ports (4.2%) were removed due to complications. Associated complications included subclavi-ana arterial puncture in 3 cases (1.4%) and local hematoma in one patient. Ventricular tachycardia occurred in one patient due to catheter was inserted into the right ventricle (0.4%). Five patients had soft tissue infections around ports (2.3%) and the ports were removed in 2 eases due to anti-infections therapy failure. Catheter dislocation happened in 2 cases (0.9%). The catheter obstruction was observed as a complication, which comprised three instances of catheter distortion and three of catheter-associated venous thrombosis, the ports in these six patients were removed (2.8%). The overall complication was 7.8%. Conclusions Totally implantable central venous access ports can provide a long-term and safe intravenous access to patients who need long-term intravenous infusion, especially for cancer patients received chemotherapy. Although the operation is simple, there are some complications and need to be carefully monitored.

BACKGROUND:Mechanical strain certainly has an effect on physiological activities of osteoblasts. Runx-2 is a target of bone morphogenic protein signal and is an important factor for regulation of osteoblastic differentiation. Bone morphogenic protein signal transduction pathway is involved in physiological response of osteoblast to stimulation of mechanical centrifugal force.
OBJECTIVE:To observe the effect of mechanical centrifugal force on bone morphogenetic protein signal pathway under different time period and speed.
METHODS:MC3T1-E1 cells were pre-treated in DMEM medium containing 10%fetal bovine serum for 24 hours, and then divided into control group, 90 r/min group, 180 r/min group and 250 r/min group. Each group was then subdivided into 6 hours, 12 hours and 24 hours centrifugation subgroups. Experiments were repeated for three times for different centrifugal speed and different time period. Except centrifugation, the control group was under the same environment. Total RNA was extracted and reversely transcribed into cDNA. Runx-2 gene expression was determined by real time fluorescent quantitative PCR.
RESULTS AND CONCLUSION:The expression of Runx-2 mRNA was increased with extension of time, showing a positive correlation between the two. The mRNA expression at 180 r/min was significantly higher than that at 90 r/min and 250 r/min (P<0.01);at 90 r/min and 180 r/min, the Runx-2 mRNA expression was higher than that in the control group (P=0.039), both of them showed significant difference along with the time. The difference of centrifugal force speed and duration is associated with different physiological response of osteoblasts in bone morphogenic protein signal pathway, which plays an important role in mechanical signal transmission and cascade reaction.

To synthesize the folic acid-alliinase conjugate(FA-Alliinase), and to study its targeting and antitumor activity on cervical cancer HeLa cells. FA-Alliinase I and FA-Alliinase II were synthesized by two methods. The couping ratios of two conjugates measured were 12 and 31, respectively. The FA-Alliinase II with high coupling ratio was selected and its structure was characterized preliminarily. The activity of alliinase retained about 50% in FA-Alliinase II determined by HPLC. The specific effect of FA-Alliinase II on HeLa cells was observed by confocal laser and flow cytometry. The antitumor activity of conjugate combined with alliin was determined by MTT, and IC50 of alliin was(127. 6±2. 3)μmol/L. This study provides a direct evaluation method for the synthesis and optimization of FA-Alliinase.

Objective: To discuss the surgical treatment and efficacy of endoscopic nipple-sparing mastectomy with skin lifting system (ENSMSLS) followed by immediate breast reconstruction. Methods: ENSMSLS was conducted on 21 patients followed by immediate breast reconstruction with implant via axillary incision from August 2014 to January 2016 in Oncology Center, Beijing Tongren Hospital, Capital Medical University. These 21 patients were frequency matched with 21 patients, who received nipple-sparing mastectomy via loop periareolar incision from November 2012 to May 2015 in the same center. These 21 patients formed the control group. The operation data of two groups were compared by t test and Fisher′s exact test. Results: Differences in operation time ((185±43) minutes vs. (165±33) minutes, t=1.778, P=0.101), amount of bleeding ((60±48) ml vs. (75±57) ml, t=-0.535, P=0.329), and drainage ((240±112) ml vs. (201±91) ml, t=1.238, P=0.233) between these two groups of patients were not statistically significant. There was no nipple necrosis recorded in the ENSMSLS group, while there were three cases (14.3%) recorded in the control group. Two cases (9.5%) of nipple transposition were recorded in the ENSMSLS group, while five cases (23.8%) were recorded in the control group. Differences in nipple necrosis and nipple transposition were statistically significant (0 vs. 5, P=0.001). There were 16 cases (76.2%) of excellent appearance recorded in the ENSMSLS group, while there were 11 cases (52.4%) recorded in the control group. There were 5 cases (23.8%) of good appearance recorded in the ENSMSLS group, while there were 9 cases (42.9%) recorded in the control group. There was no case of fair appearance in the ENSMSLS group, while there was 1 case (4.8%) recorded in the control group. Difference in postoperative appearance was statistically significant (P=0.001). Conclusions ENSMSLS significantly decreases the possibility of nipple necrosis and nipple transposition. This technique avoids visible incisions of breast. It also enhances the aesthetic appeal of reconstructed breasts.

It has been demonstrated that APPL1 (adaptor protein, phosphotyrosine interacting with PH domain and leucine zipper 1) is involved in the regulation of several growth-related signaling pathways and thus closely associated with the development and progression of some cancers. Diallyl trisulfide (DAT), a garlic-derived bioactive compound, exerts selective cytotoxicity to various human cancer cells through interfering with pro-survival signaling pathways. However, whether and how DAT affects survival of human hepatocellular carcinoma (HCC) cells remain unclear. Herein, we tested the hypothesis of the involvement of APPL1 in DAT-induced cytotoxicity in HCC HepG2 cells. We found that Lys 63 (K63)-linked polyubiquitination of APPL1 was significantly decreased whereas phosphorylation of APPL1 at serine residues remained unchanged in DAT-treated HepG2 cells. Compared with wild-type APPL1, overexpression of APPL1 K63R mutant dramatically increased cell apoptosis and mitigated cell survival, along with a reduction of phosphorylation of STAT3, Akt, and Erk1/2. In addition, DAT administration markedly reduced protein levels of intracellular TNF receptor-associated factor 6 (TRAF6). Genetic inhibition of TRAF6 decreased K63-linked polyubiquitination of APPL1. Moreover, the cytotoxicity impacts of DAT on HepG2 cells were greatly attenuated by overexpression of wild-type APPL1. Taken together, these results suggest that APPL1 polyubiquitination probably mediates the inhibitory effects of DAT on survival of HepG2 cells by modulating STAT3, Akt, and Erk1/2 pathways.

Objective The objective of this study was to investigate the proliferation,autophagy and the potential mechanism of Ubiquitin-like with PHD and ring finger domains 1(UHRF1)in lung adenocarcinoma cells. Methods The expression of UHRF1 in lung adenocarcinoma tissues was determined by the bioinformatics website(TCGA). The expression of UHRF1 in lung adenocarci-noma cell lines(PC-9,A549 and H1299)and human bronchial epithelial cells(16HBE)was detected by qRT-PCR and Western blot. After transfection of UHRF1-shRNA,CCK-8,clone formation and ki67 were performed to detect the changes in the prolifera-tive capacity of lung adenocarcinoma A549 cells. Western blot was used to detect the changes of autophagy-associated proteins(LC3-I/II and Beclin-1)and proliferation-related proteins(CDK6,Rb and PCNA). Transmission electron microscopy was used to ob-serve the effect of UHRF1 on autophagosomes in A549 cells. Results The expression of UHRF1 in lung adenocarcinoma tissues was significantly higher than that in adjacent tissues. Compared with normal bronchial epithelial 16HBE cells,the mRNA and protein levels of UHRF1 in lung adenocarcinoma A549 and H1299 cells were significantly increased. In addition,CCK-8 assay and colony forma-tion experiments showed that silencing UHRF1 reduced the growth of A549 cells. Ki-67 immunofluorescence staining showed that the proliferation ability of A549 cells after knocking out UHRF1 was significantly lower than that in the normal control group. Further-more,knockdown of UHRF1 resulted in an increased expression of CKD6 and PCNA proteins in comparison with the control-siRNA group. The expression of Rb protein was down-regulated in the UHRF1-siRNA group. Silencing UHRF1 increased the ratio of LC3-II/LC3-I, induced up -regulation of Beclin -1 expression and promoted the formation of autophagic bodies in A549 cells. Conclusion UHRF1 is highly expressed in lung adenocarcinoma,and silencing UHRF1 can inhibit proliferation. This effect may be regulated by promoting autophagy.

Objective To observe the value of ultrasound microvascular flow imaging(MV-Flow)combined with maternal serum vascular endothelial growth factor(VEGF)expression level for diagnosis of fetal growth restriction(FGR).Methods Totally 87 pregnant women with FGR(FGR group,including 43 cases of gestational week＜28 weeks[＜28 weeks subgroup]and 44 cases of ≥28 weeks[≥28 weeks subgroup])and 112 normal pregnant women with normal fetuses(normal control group,55 with gestational week＜28 weeks[NC 1 subgroup]and 57 with ≥28 weeks[NC 2 subgroup])were prospectively enrolled.MV-Flow technology was used to measure placental microvascular index(MVI),and the placental microvascular circulation was evaluated.The expression level of maternal serum VEGF was detected simultaneously,also of placental maternal surface immediately after delivery.The receiver operating characteristic curves were drawn to explore the value of placental MVI,maternal serum VEGF and the combination of placental MVI,maternal serum VEGF for diagnosing FGR.Results The levels of placental MVI and maternal serum VEGF in 2 subgroups of FGR group were both lower than those in control group(all P＜0.01).Placental VEGF expression level in FGR group was significantly lower than that in control group(P＜0.01).The area under the curve(AUC)of placental MVI,maternal serum VEGF and their combination for diagnosing FGR＜28 weeks was 0.981,0.870 and 0.997,respectively,while for diagnosing FGR≥28 weeks was 0.991,0.867 and 0.993,respectively.AUC of maternal serum VEGF alone for diagnosing in 2 subgroups of FGR were both lower than that of placental MVI and combination of placental MVI and maternal serum VEGF(all P＜0.05),while no significant difference of AUC was found between placental MVI and combination of maternal serum VEGF and placental MVI(both P＞0.05).Conclusion Both placental MVI and maternal serum VEGF level could be used to screen FGR,and the former was more valuable.

BACKGROUND: Syringomyelia is a progressive chronic disease that leads to nerve pain, sensory dissociation, and dyskinesia. Symptoms often do not improve after surgery. Stem cells have been widely explored for the treatment of nervous system diseases due to their immunoregulatory and neural replacement abilities. METHODS: In this study, we used a rat model of syringomyelia characterized by focal dilatation of the central canal to explore an effective transplantation scheme and evaluate the effect of mesenchymal stem cells and induced neural stem cells for the treatment of syringomyelia. RESULTS: The results showed that cell transplantation could not only promote syrinx shrinkage but also stimulate the proliferation of ependymal cells, and the effect of this result was related to the transplantation location. These reactions appeared only when the cells were transplanted into the cavity. Additionally, we discovered that cell transplantation transformed activated microglia into the M2 phenotype. IGF1-expressing M2 microglia may play a significant role in the repair of nerve pain. CONCLUSION Cell transplantation can promote cavity shrinkage and regulate the local inflammatory environment.Moreover, the proliferation of ependymal cells may indicate the activation of endogenous stem cells, which is important for the regeneration and repair of spinal cord injury.

OBJECTIVE To investigate the effect of gene polymorphism on opioid-induced constipation. METHODS The target genes related to opioid-induced constipation were screened out through searching guidelines， databases and evidence-based medical data， and then 100 cancer pain patients who received opioid drugs for analgesia were included as the study subjects. According to whether there were adverse effects of constipation after medication or not， they were divided into test group and control group， with 50 cases in each group. The target gene was detected by PCR or fluorescence in situ hybridization. The SNPStats program was used to carry out Hardy-Weinberg balance test and correlation analysis between gene polymorphism and opioid-induced constipation. The multivariate Logistic regression analysis was used to explore the relevant predictive factors of opioid-induced constipation， and receiver operating characteristic （ROC） curve of subjects was drawn to analyze the effectiveness of each predictive factor in predicting opioid-induced constipation. RESULTS CYP2D6， CYP3A5*3， ABCB1 and OPRM1 were selected as target genes for detection. The results of genotype detection showed that the frequency distribution of CYP2D6 （rs1065852， rs1135822， rs16947， rs28371725， rs28371735）， CYP3A5*3 （058rs776746）， ABCB1 （062rs1045642）， OPRM1 （047rs1799971） alleles were consistent with Hardy-Weinbergbalance test. The correlation analysis results showed that the proportion of genotype GG and AG in CYP3A5*3 （058rs776746， 163.com A＞G） and genotype AA and AG in OPRM1 （047rs1799971， A＞G） of patients was significantly higher in test group than that in the control group （P＜0.05）. Multivariate Logistic regression analysis showed that medication duration， CYP3A5*3 and OPRM1 gene polymorphism could be used as predictors of opioid- induced constipation in patients （P＜0.05）. The ROC curve analysis results showed that the areas under the ROC curves for medication duration and CYP3A5*3， OPRM1 gene polymorphism were 0.648， 0.640 and 0.670， respectively， with the optimal cutoff values of 124.0， 0.5 and 0.5， respectively. CONCLUSIONS Genotype GG and AG in CYP3A5*3 （058rs776746，A＞G） and genotype AA and AG in OPRM1 （047rs1799971，A＞G） are associated with opioid-induced constipation， which are expected to become clinical predictors of opioid-induced constipation， and more attention should be paid to the occurrence of constipation in patients who have been taking opioids for a long time.