Non-small cell lung cancer(NSCLC) is one of the most life-threatening human malignancies due to its high morbidity and mortality rates.Molecular targeted therapy is promising in treating some patients with NSCLC.However,it is still challenging to select proper candidates.The EML4-ALK fusion oncogene represents a novel molecular target which appears mainly in lung adenocarcinoma,and appears to be a potential biomarker associated with resistance to EGFR tyrosine kinase inhibitors.This review was intended to outline current status of preclinical and clinical research of this molecule.

Objective:To determine the effects of silencing glucose regulated protein ( GRP94 ) on the proliferation and apoptosis of breast carcinoma MCF7 cells. Methods:Chemically synthesized siRNA targeting GRP94 gene and transfected into MCF7 cells used by Liopfectamine RNAIMAX. The mRNA and protein expression levels of GRP94,cyclinD1,Bax and Bcl-2 were detected by Real-time PCR and Western blot. CCK8 assay was used to detect the effect of specific GRP94 siRNA on cell proliferation and the effect on cell cycle and apoptosis were analyzed by flow cytometry and Hoechst 33258 staining. Results:Compared with the siRNA-NC cells, the expression of GRP94 was significantly down-regulated in MCF7 cells. Knockdown of GRP94 in MCF7 cells decreased cell proliferation and promoted cell apoptosis. The expression of cyclinD1and Bcl-2levels were significantly reduced, and Bax level was increased in siRNA-GRP94 MCF7 cells. Conclusion: The siRNA-mediated GRP94 silence significantly inhibits MCF7 cell proliferation,promoted cell apoptosis by down-regulating cyclin D1,Bcl-2 expression and up-regulating the Bax expression in MCF7 cells.

Background and purpose:We investigated whether lfuorine-18 lfuorodeoxyglucose (18F-FDG) maximal standard uptake value (SUVmax) of the primary tumor (SUV-T), SUVmax of the regional lymph nodes (SUV-N) or the overall loco-regional lesion SUVmax (SUV-TOTAL) was related to survival of patients with stage Ⅲ non-small cell lung cancer (NSCLC) who received Cetuximab and combined definitive chemoradiotherpay. Methods:From September 2009 to July 2012, seventeen patients with unresectable stageⅢNSCLC receiving cetuximab with cisplatin/vinorelbine (NP) followed by concomitant NP and intensity-modulated radiotherapy (IMRT) at the Fudan University Shanghai Cancer Center were enrolled onto a prospectively study. All patients received positron emission tomography/computerized tomography (PET/CT) scans within 2 weeks before enrolment. Univariate analysis were used to assess the correlation between SUV-T, SUV-N, SUV-TOTAL, gender, age, histology, tumour-node-metastasis (TNM) stage, performance status (PS) as well as smoking status and survival. The factors which showed statistical signiifcance entered into multivariate Cox-regression model. Survival functions of different populations were estimated by Kaplan-Meier method and compared by Log-rank test. Results:In the univariate analysis, SUV-T, SUV-N, SUV-TOTAL, PS and smoking status were prognostic factors. The best cut-off values for SUV-T, SUV-N and SUV-TOTAL were 11, 11 and 20, respectively. Multivariate analysis revealed that SUV-TOTAL (P=0.012), SUV-T (P=0.025), and SUV-N (P=0.033) were independent predictors of survival with hazard ratio (HR) of 14.7, 11.2, and 6.2, respectively. Conclusion:Local, regional and locoregional maximal SUVs deifned by 18F-FDG PET-CT scanning may have a strong correlation with survival in this patients setting, which merits further study.

Background and purpose:Radiomics is an emerging field that generates large amounts of valuable clinical information through extracting quantitative imaging features. The purpose of this study was to use the radiomics approach to assess the value of features captured from PET and CT in predicting the therapeutic effect in stageⅠ non-small cell lung cancer (NSCLC) after stereotactic ablative radiotherapy (SABR).Methods:Patients with stageⅠ NSCLC conifrmed by pathology and treated with SABR were included retrospectively. The gross tumor volume (GTV) was deifned by two radiologists. PET and CT scan images were collected, and radiomic features were further extracted and analyzed. Non-negative matrix factorization was used to distinguish patients with or without local control.Results:Sixteen patients were eligible for analysis. This study identiifed two PET features (LL_GLCM_Maximal_Correlation_Coeffcient and HL_GLRMS_LRE) captured from PET/CT as having signiifcance in classifying patients with or without disease development. This study not ifnd similar results in CT scans.Conclusion:It seems feasible to use radiomics information effects from PET/CT to predict therapeutic effects of SABR in stageⅠ NSCLC. Further investigation is needed.

Aim To investigate ALEX1 gene expres-sion in cervical cancer tissues and adjacent non-can-cerous tissues, and to explore the ALEX1 genetic influ-ence on cell proliferation,cycle and apoptosis of human cervical cancer cell line HeLa. Methods ALEX1 protein expression in cervical cancers and in non-can-cerous cervical tissues was evaluated using immunohis-tochemical method. A small interference RNA targeting ALEX1 gene was transfected into HeLa cells′, and the effect of ALEX1 interference on HeLa cells′ cycle and apoptosis was analysed by flow cytometry. The effect of ALEX1 interference on HeLa cells′ proliferation and sensitivity to resveratrol was analysed by CCK-8 assay. Results ALEX1 protein expression was significantly increased in cervical cancer tissues compared with non-cancerous tissues. HeLa cells′proliferation was inhibi-ted compared with control group and blank group. He-La cells′ sensitivity to resveratrol was enhanced com-pared with control group blank group. Conclution SiRNA silencing of ALEX1 gene could significantly in-hibit HeLa cells′ proliferation and enhance resveratrol ability of inhibiting HeLa cells′proliferation.

Background and purpose:Clinical data show that Endostar, a recombinant human endostatin, has the therapeutic beneift for patients with non-small cell lung cancer (NSCLC) while combined with chemotherapy or ra-diotherapy. However, the microenvironment changes induced by Endostar monotherapy in NSCLC is not yet clear. The purpose of this study was to prospectively study tumor vascular effects of Endostar monotherapy in patients with locally advanced or advanced NSCLC by dynamic contrast-enhanced perfusion computed tomography (CT perfusion, CT-p). Methods:Previously untreated patients with histologically or cytologically conifrmed locally advanced or advanced NSCLC were eligible. All patients received daily Endostar (7.5 mg?m2) for 14 days. CT-p scans were acquired at the baseline and post-treatment. CT-p parameters, such as blood lfow (BF), blood volume (BV) and permeability surface PS (area product), were measured in all patients.Results:Of all 7 patients enrolled, four were staged asⅢB and three as stageⅣ (2 with malignant pleural effusion, 1 with brain metastasis). The median BF, BV and PS values of baseline and post-treatment were 27.1/48.9 mL/100 mL/min, 86.8/84.8 mL/100 mL and 45.0/54.0 mL/100 mL/min, respectively. After administration of Endostar for 14 days , BF showed a signiifcant increase compared with that at baseline (P=0.028), whereas no signiifcant changes were found in BV (P=0.398) and PS (P=0.237) values.Conclusion:Our results suggest that Endostar monotherapy induces a signiifcant increase in BF whereas no signiifcant difference in BV and PS.

Objective:To investigate the effects of ALEX1 overexpression on cell proliferation and apoptosis of human breast cancer cell line MCF-7.Methods: MCF-7 cells were infected recombinant lentivirus LV5-ALEX1 and the negative control lentivirus LV5-NC,respectively.After 72 h, the expression of ALEX1 was detected by Real-Time PCR and Western blot.CCK8 assay were performed to observe the proliferation ability after 24 h, 48 h, 72 h, 96 h.The effect of overexpression ALEX1 on apoptosis was determined by flow cytometry.The level of Bax,BCL-2 and active caspase3 was detected by Western blot.Results:The mRNA level of ALEX1 markedly increased after 72 h(165.81±12.14 vs 52.29±2.32,P<0.01).In CCK8 assay,the results revealed that the cell pro-liferation was inhibited compared with control group in 48 h,72 h,96 h( P<0.05).The results revealed that overexpression of ALEX1 enhanced MCF-7 apoptosis(20.55%±2.50 % vs 3.60%±1.614%,P<0.05).The results by Western blot showed that the protein levels of Bax and active caspase were increased in LV5-ALEX1 group compared with LV5-NC group.However,the protein levels of BCL-2 was decreased in LV5-ALEX1 group compared with LV5-NC group.Conclusion:Overexpression of ALEX1 significantly reduced MCF-7 cancer cells proliferation and induced MCF-7 cells apoptosis.

Hepatolithiasis is a common and persistent disease in hepatobiliary surgery, which is one of the most important leading causes of death in patients with benign biliary tract diseases. Traditional of diagnosis and treatment options of hepatolithiasis have limitations, recently the rising of three-dimensional visualization technology provides doctors with fresh thinking and approaches. Three-dimensional visualization technology can accurately evaluate the anatomical structure and pathological condition of the liver, at the same time it plays an important role in guiding hepatectomy, choledochoscopic lithotripsy and biliary drainage. Three-dimensional printing and intraoperative navigation, which based on three-dimensional visualization technology, also has good application prospects. This paper summarized the application of three-dimensional visualization technology for the diagnosis and treatment of hepatolithiasis in order to help the future research.

The reversible and precise temporal and spatial regulation of histone lysine methyltransferases(KMTs)is essential for epigenome homeostasis.The dysregulation of KMTs is associated with tumor initiation,metastasis,chemoresistance,invasiveness,and the immune microenvironment.Therapeutically,their promising effects are being evaluated in diversified preclinical and clinical trials,demonstrating encouraging outcomes in multiple malignancies.In this review,we have updated recent understandings of KMTs'functions and the development of their targeted inhibitors.First,we provide an updated overview of the regulatory roles of several KMT activities in oncogenesis,tumor suppression,and im-mune regulation.In addition,we summarize the current targeting strategies in different cancer types and multiple ongoing clinical trials of combination therapies with KMT inhibitors.In summary,we endeavor to depict the regulation of KMT-mediated epigenetic landscape and provide potential epigenetic targets in the treatment of cancers.

Objective:To evaluate the auxiliary diagnosis value of bacterial culture, polymerase chain reaction (PCR) and serum anti-pertussis toxin immunoglobulin G (AntiPT-IgG) level detection in suspected pertussis.Methods:A total of 110 suspected cases of pertussis treated in the Department of Pediatrics of Wuhu No.1 People′s Hospital from June 2018 to May 2019 were recruited for the study.The nasopharyngeal swabs of all cases were collected for Bordetella pertussis culture and specific nucleic acid PCR detection.Serum samples of 78 cases were collected for the detection of AntiPT-IgG level by enzyme linked immunosorbent assays.Results:The positive rates of bacterial culture group and PCR group were 21.8% and 30.0%, respectively, with no statistically significant difference ( χ2=1.198, P>0.05). The culture positive rate of cases with the duration of cough<2 weeks was 32.1%, which was signi-ficantly higher than that of cases with the duration of cough about 2-4 weeks (14.3%) or >4 weeks (9.1%) ( χ2=6.522, P<0.05). The PCR positive rate of cases with the duration of cough <2 weeks was 39.6%, which was also significantly higher than that of cases with the duration of cough about 2-4 weeks (25.7%) or > 4 weeks (13.6%) ( χ2=6.126, P<0.05). The mean value for serum AntiPT-IgG level of 78 cases was (75.727±78.454) IU/mL, the median AntiPT-IgG levels of cases with the duration of cough<2 weeks and about 2-4 weeks were 5.909 IU/mL and 20.948 IU/mL, respectively, and the positive rates were 14.7% and 38.1%, respectively.The AntiPT-IgG level of cases with the duration of cough> 4 weeks and that at convalescent stage were (79.281±68.254) IU/mL and (107.242±75.750) IU/mL, and the positive rates were 39.1% and 57.1%, respectively. Conclusions:In the vaccine era, the results of pathogenic and serological tests should be combined to assist the clinical diagnosis of pertussis.The positive rate of bacterial culture and specific nucleic acid pathogen detection in children with cough duration less than 2 weeks is high, and the serological diagnosis is more effective after the duration of cough is over 4 weeks.