ObjectiveTo observe and assess the efficacy and safety of different dosages of apatinib mesylate on advanced hepatocellular carcinoma（HCC）. 
MethodsIt was a prospective， randomised， openlabeled， two dosages， national multicentre， and phase Ⅱ clinical trial. From June 2010 to July 2013， a total of 121 advanced HCC patients who had not received any systemic treatment（including molecular targeted therapy and systemic chemotherapy） were enrolled from 16 centers in China. First， 104 patients were randomly allocated in a 1：1 ratio to two cohorts to receive oral apatinib at an initial dosage of 750 mg qd（n=51） or 850 mg qd（n=53）. To further explore the safety of high dosage（850 mg qd）， 17 patients were recruited to receive apatinib 850 mg qd， thus the sample of 850 mg cohort was expanded to 70 cases. The primary endpoint was median time to progression（TTP）， and the secondary endpoints included overall survival（OS）， objective response rate（ORR）， disease control rate（DCR） and adverse events（AEs）. Tumor response and AEs were evaluated according to RECIST 11 criteria and NCI CTC 40 criteria respectively. 
ResultsThe TTP of patients treated with 750 mg and 850 mg apatinib were 332 months（95％CI：2045.86 months） and 421 months（95％CI：2.14-5.86 months）， and the median OS were 9.82 months（95％CI：5.71-12.07 months） and 971 months（95％CI：6.61-12.04 months）， respectively. ORR was 2.0％ and 10.0％， and DCR were 647％ and 58.6％， respectively. No statistical differences in the above efficacy indexes were found between the two dosages（P＞0.05）. The drugrelated AEs of grade≥3 occurred in 58.8％ and 586％ patients receiving 750 mg and 850 mg apatinib（P＞005）， respectively. No unexpected AEs occurred. 
ConclusionApatinib can be used for advanced HCC. Apatinib at an initial dosage of 750 mg or 850 mg qd orally has equal efficacy and safety in advanced HCC patients with good tolerance. Hence，oral administration ofapatinib 750 mg qd is recommended for the further phase Ⅲ clinical trial.

ObjectiveTo observe and analyze the appearance of cutaneous capillary endothelial proliferation（CCEP） in clinical trials of primary hepatic carcinoma treated with domestic antiPD-1 monoclonal antibody SHR-1210. 
MethodsFrom Nov 1, 2016 to Sep 30, 2017， SHR-1210 was used to treat primary hepatic carcinoma in our hospital. Among them， single drug group： SHR-1210 3 mg／kg iv q2W or 3 mg／kg iv q3W. The combined group A： SHR-1210 3 mg／kg iv q2W； apatinib starting dose 125 mg po qd. The combined group B： SHR1210 3 mg／kg iv q2W； FOLFOX 4 regimen（oxaliplatin 85 mg／m2 iv d1； leucovorin 200 mg／m2 iv d1， d2； fluorouracil 400 mg／m2 iv d1，d2； fluorouracil 600 mg／m2 CIV d1，d2， q2W）. The incidence of CCEP was observed during SHR-1210 treatment and classified according to the shape. Pathological examinations were performed in some patients and 2 typical cases were shared. 
ResultsThirtyeight patients received SHR1210 monotherapy， including 2 weeks group（n=16） and 3 weeks group（n=22）， all of which were hepatocellular carcinoma. There were 6 cases in SHR1210 combined with apatinib group， including 2 cases of hepatocellular carcinoma， and 4 cases of cholangiocarcinoma. There were 18 cases in SHR1210 combined with FOLFOX 4 regimen group， including 8 cases of hepatocellular carcinoma and 10 cases of cholangiocarcinoma. CCEP can be observed in 59 patients treated with SHR1210 at least 2 times. CCEP were divided into “rednevus”， “pearl”， “mulberry”， “patch” and “tumor type” according to morphological features. The total incidence rate of CCEP of SHR1210 monotherapy was 77.1％（27／35）. The incidence of CCEP in the combined A group and the combined B group was 33.3％（2／6） and 611％（11／18）， respectively. Among the 45 patients could be evaluated, CCEP was found in 35 cases. Patients with CCEP achieved PR 31.4％（11／35）， SD 14.3％（5／35） and PD 543％（19／35）， while those without CCEP got SD 40％ and PD 60％. The response rate of patients with CCEP was significantly higher than those without CCEP， but there was no statistical difference（P=0.105）， which may be related to the small sample size. 
ConclusionCCEP is the most common and drugrelated adverse event in clinical trials of SHR1210 for primary hepatic carcinoma. Its pathogenesis is still unclear and maybe related to the immune response caused by SHR1210. CCEP often take place on the skin of face and body surface, never on the mucosa of respiratory tract and digestive tract. It is preliminarily observed that patients with CCEP tend to have higher response rate during SHR1210 monotherapy. SHR1210 combined with apatinib or FOLFOX 4 regimen can reduce the incidence of CCEP， and the specific mechanism of it needs further study.

ObjectiveTo investigate the effect of regulating glucose metabolism by silent information regulator 6 （SIRT6） on radiosensitivity of nonsmall cell lung cancer A549 cells. MethodsThe adenovirus vector AdSIRT6 expressing SIRT6 was constructed， and mRNA levels of SIRT6 were detected by fluorescence quantitative realtime PCR （QPCR） at 24 h after transfection with different transfection intensities （0， 25， 50， 100， 200 pfu／cell） of AdSIRT6. According to the experimental design， A549 cells were divided into control group， empty load（Adnull） group and overexpression （AdSIRT6） group， and the virus concentration of Adnull group and AdSIRT6 group were 200 pfu／cell. The survival fraction （SF） of 3 groups after 0， 2， 4， 6， 8 and 10 Gy Xray irradiation were detected by colony formation assay， and the cell survival curve was drawn and the sensitivity enhancement ratio （SER） was calculated according to the multitarget model. Flow cytometry was used to detect the cell cycle and apoptosis at 48 h in 3 groups after 4 Gy Xray irradiation. The mRNA levels of pyruvate dehydrogenase 2 （PKM2）， lactate dehydrogenase A （LDHA） and hexokinase （HK） in glycolysis were detected by QPCR after 48 h irradiation with 4 Gy Xray. Glucose levels were measured by glucose kit after transfection for 12， 24， 36 and 48 h. 
ResultsQPCR results showed that in the range of 25200 pfu／cell， the mRNA levels of SIRT6 increased with the increasing intensity of transfection （P＜0001）. The mRNA levels of SIRT6 were 1012±0016， 1356±0185， 2243±0695， 4887±1169 and 7241±1425 for A549 cells transfected with 0， 25， 50， 100， 200 pfu／cell. The mRNA levels of SIRT6 were higher in 50， 100， 200 pfu／cell than in control group （P＜005）， and the followup test selected the strongest expression of 200 pfu／cell. The clone formation experiment showed that there was no significant difference in SF between Adnull group and control group after 0， 2， 4， 6， 8 and 10 Gy Xray irradiation （P＞005）， while the SF in AdSIRT6 group after 410 Gy Xray irradiation was lower than that in Adnull group and control group （P＜005）. The cell survival curve of the multitarget model showed that the SER was 176. Compared with control group and Adnull group， the percentage of G0／G1 phase cells and apoptotic rate in AdSIRT6 group were increased， while the percentage of S phase cells and the mRNA levels of PKM2， LDHA and HK were decreased （P＜005）. The glucose consumption of AdSIRT6 group decreased after 12， 24， 36 and 48 h of transfection， lower than those of control group and Adnull group （P＜005）. 
ConclusionOverexpression of SIRT6 can inhibit the formation of key enzymes during glycolysis in A549 cells to inhibit glycolysis as well as radiosensitivity， and lead to G0／G1 arrest and apoptosis.

ObjectiveTo investigate the effects and mechanisms of phloretin on the proliferation and apoptosis of human small cell lung cancer H446 cells. 
MethodsH446 cells were treated with 20， 30 or 40 μg／ml phloretin， and cells untreated were set as control. The proliferative rate of H446 cells treated with phloretin for 24， 48 and 72 h was detected by MTT assay； Apoptosis of cells treated with varied doses of phloretin was evaluated by flow cytometry method； The content of cytochrome C in cytosol was assessed by Western blotting method； Besides， mRNA expression of procaspase3， Bax and Bcl2 were examined by realtime PCR（QPCR）. 
ResultsThe dose of 20， 30 or 40 μg／ml phloretin could inhibite the proliferation of H446 cells in a dose and time dependent manner（P＜0.05）. Flow cytometry method showed that the apoptotic ratio of control group was（4.23±0.25）％， much lower than（12.97±0.21）％，（18.48±0.24）％ and（33.61±0.27）％ treated by 20， 30 or 40 μg／ml phloretin. Besides， the protein content of cytochrome C in cytosol was upregulated by phloretin in a dosedependent manner（P＜005）. Phloretin could dosedependently decrease the expression of Bcl2 mRNA（P＜0.05） and increase the mRNA expression of procaspase3 and Bax（P＜005）. 
ConclusionPhloretin can inhibit the proliferation of H446 cells and induce apoptosis by interfering the release of cytochrome C from mitochondria to cytosol and the mRNA expression of procaspase3， Bax and Bcl-2.

ObjectiveTo investigate the effect of naringin on proliferation， apoptosis and migration on ovarian cancer cell line SKOV3. MethodsNaringin of 1， 5， 10， 20 μmol／L was used to treat SKOV3 cells at logarithmic growth phase. SKOV3 cells without naringin treatment were used as control. The proliferation of cells treated with naringin at different concentrations at 48 h and 20 μmol／L naringin for 12， 24， 36 and 48 h were detected by MTT assay. SKOV3 cells treated with different concentrations of naringin for 48 h were collected. AnnexinVFITC／PI double staining and PI single staining flow cytometry were used to detect the apoptosis and cell cycle of SKOV3 cells， respectively. Transwell method was used to evaluate the migration ability by detecting the number of cell penetrating membrane. The relative levels of pAkt and PTEN were detected by Western blotting. 
ResultsMTT detection showed that following treatment with naringin at 1， 5， 10， 20 μmol／L for 48 h， the proliferative rate of SKOV3 cells decreased. In addition to 1 μmol／L， the proliferative rates of SKOV3 cells treated with 520 μmol／L were lower than control group （P＜0.05）. The proliferative rates were （61.95±6.87）％ and （50.58±6.09）％ of 10 and 20 μmol／L at 48 h， and there was no significant difference （P＞0.05）. The proliferative rates were （83.93±5.54）％， （73.10±3.58）％， （61.95±5.01）％ and （53.00±7.67）％ of 20 μmol／L at 12， 24， 36 and 48 h， were lower than those of control group （P＜0.05）. Compared with control group， the proportion of cells at G0／G1 phase and the apoptotic rate increased， while the proportion of cells at S phase decreased in cells exposure to 120 μmol／L naringin at 48 h （P＜0.05）.Following treatment with 1， 5， 10 and 20 μmol／L naringin， the number of cell penetrating membrane was 61.83±6.77， 47.17±5.35， 32.17±5.95 and 2083±306， the relative levels of pAkt were 0545+0050， 0.373+0.035， 0.280+0.054 and 0.173+0.034， and the relative levels of PTEN were 0.357+0.054， 0.468+0.085， 0602+0.063 and 0.728+0.03， better than those of control group （P＜0.05）. 
ConclusionNaringin can significantly inhibit the proliferation of ovarian cancer cell line SKOV3， promote its apoptosis， and reduce its invasive ability， which may be related to the inhibition of PTEN／Akt signaling pathway activation. It provides a possible clue for the clinical treatment of ovarian cancer.

ObjectiveTo investigate the effects of aspirin combined with trastuzumab on proliferation and apoptosis of HER-2positive breast cancer cell line SKBR-3. MethodsThe SKBR-3 cells were divided into four groups： control group， aspirin group （5 mmol／L）， trastuzumab group （30 μg／ml） and combination group （5 mmol／L aspirin+30 μg／ml trastuzumab）. MTT assay and flow cytometry were used to observe the effects of different drug treatment on cell proliferation and apoptosis. 
ResultsMTT assays showed that the relative proliferation rate of SKBR3 cells was （79.6±2.61）％ in aspirin group， （48.2±3.35）％ in trastuzumab group and （21.5±166）％ in combination group. Compared with aspirin group or trastuzumab group， the cell proliferation of combination group was significantly inhibited （P＜0.05）. Two drugs combined effect index was 10 of a superimposition effect. The apoptosis assays showed that the relative apoptotic rate of cells was （27.3±3.47）％ in aspirin group， （35.3±2.80）％ in trastuzumab group and （56.2±3.95）％ in combination group. Compared with aspirin group or trastuzumab group， the cell apoptosis of combination group was significantly increased （P＜0.05）. ConclusionAspirin combined with trastuzumab can effectively inhibit the growth of HER-2positive breast cancer cells， which may be a new model for the clinical treatment of HER-2positive breast cancer.

ObjectiveTo investigate the leptin （LEP） level and the association of its single nucleotide polymorphisms （SNPs） with susceptibility to nonsmall cell lung cancer （NSCLC）. MethodsFrom January 2014 to December 2016， peripheral blood samples were collected from 142 cases of NSCLC patients following pathological diagnosis. Using the Sequenom MassARRAY system via matrix assisted laser desorption ionization timeofflight mass spectrometry （MALDITOFMS）， LEP polymorphism of rs4731423， rs10487506， rs2167270， rs17151919， rs1800564 and rs11761556 were genotyped. The peripheral blood samples of 176 healthy controls were selected for comparison. The distribution of SNPs genotypes and alleles in NSCLC patients and healthy controls were compared. The odds ratio （OR） and its 95％ confidence interval （95％CI） were calculated to evaluate the relationship between SNPs and NSCLC susceptibility. The serum LEP levels in patients with NSCLC were measured by radioimmunoassay. The relationship of serum LEP level with clinicopathological parameters， including gender， age， pathological type， tumor size， TNM stage and lymph node metastasis and LEP SNPs were analyzed. 
ResultsThe distribution of rs4731423， rs10487506， rs2167270 and rs11761556 genotypes in 142 NSCLC patients and 176 healthy controls was in accordance with HardyWeinberg balance. There was no significant difference in genotype and allele distribution of rs10487506 and rs11761556 between NSCLC group and control group （P＞0.05）. Regarding rs4731423 distribution， the frequency of GG genotype in NSCLC group was 317％ （45／142）， and the allele frequency of G was 514％ （146／284）， higher than 18.8％ （33／176） and 372％ （131／352） in control group （P＜0.05）. As for the rs2167270 distribution， the frequency of AA genotype in NSCLC group was 155％ （22／142）， higher than 74％ （13／176） of control group， and the difference was statistically significant （P＜0.05）. However， there was no significant difference in the frequency of allele distribution between both groups in term of rs2167270 （P＞0.05）. LEP rs10487506， rs2167270 and rs11761556 were not associated with the risk of NSCLC （P＞0.05）. For rs4731423， as compared to AA genotype， GG and AG+GG genotypes increased the risk of NSCLC to 2594 and 1961 folds （P＜0.05）， but AG did not change the risk of NSCLC （P＞0.05）. When taking A allele as the reference， risk of G allele for NSCLC increased to 1785 folds （P＜0.05）. The level of LEP was independent of gender， age， pathological type， lymph node metastasis， rs10487506， rs2167270 and rs11761556， but related with tumor size， TNM stage and rs4731423 （P＜0.05）. The serum LEP levels of AG， GG and AG+GG were higher than AA， and the difference was statistically significant （P＜0.05）. ConclusionLEP rs4731423 was related to NSCLC susceptibility and LEP level. The risk of NSCLC and LEP level increased for G allele carriers， presenting a certain value in the screening of NSCLC susceptible population.

ObjectiveTo investigate the expression of ULK1 in gastric cancer tissues and its clinical significance. 
MethodsFrom Jan 2013 to Dec 2013， 145 cases of gastric cancer and 50 cases of adjacent tissues were enrolled， and the expression of ULK1 in the above tissues was detected by immunohistochemical SP method. The relationship of its expression and clinicopathological parameters as well as prognosis were analyzed. 
ResultsThe positive expression of ULK1 in gastric cancer and adjacent tissues were 80％ （116／145） and 16％ （8／50）， respectively， with statistical difference （P＜0.05）. The expression of ULK1 was correlated with invasion depth， differentiation degree， lymph node invasion， TNM stage， recurrence and metastasis （P＜0.05）， but not with age， invasion of vascular， expression of HER2 and p53 （P＞005）. The median overall survival of patients with ULK1 negative， weakly positive and positive expression was 448 months （95％CI：40.5-49.2 months） and 427 months （95％CI：39.9-45.6 months） and 377 months （95％CI：33.0-42.4 months）， and the difference was statistically significant （P=0.007）. ConclusionULK1 is highly expressed in gastric cancer tissues， and there is a poor prognosis in patients with ULK1 positive expression. ULK1 may be involved in the occurrence and development of gastric cancer， and is one of the prognostic indicators of gastric cancer.

ObjectiveTo investigate the protein expression of cell divison cycle 6（CDC6） and minichromosome maintennance 7（MCM7） in early gastric cardia cancer tissues and its clinical significance. MethodsFrom Mar 2009 to Dec 2014, 57 cases of early gastric cardia cancer tissues and paired adjacent normal tissues were collected. The expression of CDC6 and MCM7 in the above tissues were detected by immunohistochemistry.Furthermore， the relationships between protein levels of CDC6 and MCM7 with clinical features as well as prognosis were analyzed. ResultsThe positive rate of CDC6 expression in early gastric cardia cancer tissues was 33.3％， higher than that in adjacent tissues（14.0％）， and the difference was statistically significant（P＜0.05）.The positive rate of MCM7 expression in early cardia cancer tissues was 66.7％， higher than that in adjacent tissues （19.3％）， and the difference was statistically significant （P＜0.01）.The expression of CDC6 and MCM7 in early gastric cardia cancer tissues was both correlated with tumor differentiation（P＜0.05）， but not with age， gender and tumor volume（P＞0.05）. There was no significant correlation between CDC6 and MCM7（r=0.105， P＞0.05）. The overall survival of patients with different expression of CDC6 and MCM7 were not achieved. Patients with positive expression of CDC6 had better overall survival than those with negative expression， but the difference was not statistically significant （P=0.149）. Patients with positive expression of MCM7 had worse overall survival than those with negative expression， but the difference was not statistically significant （P=0.710）. ConclusionDysregulation of CDC6 and MCM7 expression occurs in early stage during the development of cardia cancer， and they are correlated with tumor differentiation， and may be related to the occurrence and development of cardia cancer.

ObjectiveTo explore the expression of receptor tyrosine kinase EphB6 in gastric cancer tissues and its relationship with clinicopathological characteristics. 
MethodsThe expression of EphB6 in 152 gastric cancer and paired adjacent normal tissues was detected by immunohistochemistry. The relationship between the expression of EphB6 and clinicopathological parameters was analyzed. ResultsIn 152 cases of gastric cancer, the low expression of EphB6 was found in 66 cases （43.4%）， moderate expression in 54 cases（35.5％）， and high expression in 32 cases （21.1％）. The expression of EphB6 was high expressed in adjacent normal tissues. The expression of EphB6 was associated with differentiation， lymph node metastasis and TNM stage （P＜0.05）， but not related to age， gender， tumor location and depth of tumor invasion （P＞0.05）. ConclusionThe expression of EphB6 protein was decreased in gastric cancer and related to lymph node metastasis. It may be a potential marker to predict the metastasis of gastric cancer.

ObjectiveTo detect the expression of long noncoding RNAs （lncRNAs） in gastric cancer and analyze its function. MethodsRNASeq data of 34 paired gastric cancer and normal adjacent tissues were downloaded from the website of the Cancer Genome Atlas （TCGA）. Subread and featureCounts were used to analyze the data. The expression of mRNAs and lncRNAs was obtained. EdgeR was utilized to identify the differentially expressed lncRNAs between gastric cancer and normal adjacent tissues. The mRNAs coexpressed with the differentially expressed lncRNAs were identified and subjected to Gene Ontology （GO） and Kyoto Encyclopedia of Genes and Genomes （KEGG） analysis. ResultsOne thousand three hundred and fortyfive lncRNAs were differentially expressed between gastric cancer and normal adjacent tissues. Among these lncRNAs， 758 lncRNAs were upregulated and 587 lncRNAs were downregulated in gastric cancer. Coexpression analysis showed that 1045 coding genes were correlated with lncRNAs. The GO biological process terms associated with coexpressed mRNAs included mitotic nuclear division， cell division， DNA replication， etc. The KEGG pathways involved cell cycle， cell adhesion molecules， etc. ConclusionThe expression of lncRNAs in gastric cancer changes significantly compared with normal adjacent tissues， suggesting lncRNAs may play important roles in development and progression of gastric cancer.

ObjectiveTo investigate the efficacy and the application value of MosaiQ system in imageguided radiotherapy（IGRT）. MethodsFrom 8 Jan 2014 to 30 May 2017, 510 patients with malignancies receiving IGRT were enrolled. The setup errors required from the first trial and the final trial， and the accelerator treatment bed values before IGRT and after the calibration position were recorded. The tumor setup errors and the treatment accuracy of radiotherapy were analyzed statistically. ResultsThe setup errors of Y direction were the largest compared with X and Z directions（P＜0.05）. Abdominal tumor setup errors were the largest compared with head， head and neck， chest， abdomen and pelvis（P＜0.05）. The difference between the first trial and the final decision had no statistical significance （P＞0.05）， and the mean value of setup errors was less than 2 mm. The treatment accuracy for all parts had no differences （P＞0.05）， and the accuracy was more than 800％. The accuracy of Y direction was 84.7％， lower than X and Z directions （P＜0.05）. ConclusionMosaiQ system can achieve allround monitoring of IGRT， improve the accuracy of treatment， and provide theoretical and data support for quality control and assurance in the department of radiotherapy.

ObjectiveTo evaluate the value of contrastenhanced ultrasound（CEUS） guided biopsy in hepatic lesions. MethodsA total of 33 patients with 35 lesions underwent contrastenhanced ultrasound guided biopsy from Jan 2016 to Jan 2017 were enrolled in this study. Guided by contrastenhanced ultrasound， the puncture site and needle path were selected and guided realtime biopsy was performed. Puncture successful rate and diagnostic accuracy were calculated. ResultsAll the patients were performed successfully， and each lesion was punctured twice. The puncture successful rate was 1000％. Among 33 patients， 28 cases were diagnosed with malignancies （13 cases of hepatocellular carcinoma， 10 cases of cholangio cellular carcinoma， 3 cases of neuroendocrine carcinoma， 1 case of metastatic urothelial carcinoma and 1 case of metastatic squamous cell carcinoma）， and 5 cases were benign（2 cases of inflammatory lesions， hepatocellular adenoma in 1 case and dysplasia nodules in 2 cases）. The diagnostic accuracy was 1000％. Puncture complication was found in 1 case （small amount of bleeding under hepatic capsule）. ConclusionContrastenhanced ultrasound can clearly display intrahepatic lesions， and realtime biopsy can improve the positive rate of puncture diagnosis.

Natural killer T （NKT） cell is a kind of important independent lymphocyte subsets. Studies have shown that it plays an important role in the process of the bodys immune response. Different NKT cells and their functions have been found and the influence of different subsets of tumor immune is not the same. The interaction mechanism between subsets is not very clear and needs further exploration. An indepth understanding of NKT cells in the tumor immune function has important significance for the treatment of tumors.

Thyroid tumor is one of the most common endocrine tumors. Recent epidemiological studies show that the incidence of thyroid carcinoma is increasing rapidly. Erythropoietin producing hepatocyte （Eph） gene as the largest family of tyrosine kinase receptors， is found to be involved in many physiological and pathological processes， and its role in tumorigenesis is attracting more and more attention. Eph receptors are overexpressed in many human malignancies and are associated with tumor growth， invasion， metastasis， and angiogenesis. Research shows that the expression level of Eph receptor in thyroid carcinoma is significantly increased, which plays an important role in the occurrence， development and metastasis of thyroid carcinoma and has broad prospects for early diagnosis and treatment of thyroid carcinoma.

Pulchinenoside D is the most widely and the highest titer monomer of many effective monomer components of Baitouweng in antitumor researches， which is one of the research hotspots of antitumor drugs in recent years. Pulchinenoside D inhibits tumor survival by inhibiting proliferation and promoting apoptosis of tumor cells， inhibiting energy metabolism， regulating autophagy and inhibiting tumor cell migration and metastasis. In this review， we collected related studies on antitumor of pulchinenoside D in recent years， which may provide new ideas for tumor treatment.