Recently,targeted therapy plays an important role in the treatment of non-small cell lung cancer.Crizotinib,the first generation of anaplastic lymphoma kinase( ALK) tyrosine kinase inhibitor,has been ap-proved for the treatment of ALK-rearranged NSCLC in the US since 2011.However,the crizotinib therapy is ef-fective only in the early stage of treatment.After a long time treatment,therapy resistance will follow because of the emerging second mutation of the tumor cell.In recent years,as the second generation of anaplastic lymphoma kinase tyrosine kinase inhibitor, alectinib has been approved in Japan for the treatment of ALK -rearranged NSCLC patients.Thus,research progress of Alectinib for NSCLC therapy is summarized in this article.

The DNA copy-number variant (CNV) is a kind of segments of DNA ranging from 1 kb to 3 Mb that is present in a variable number of copies.CNVs widely distribute across the human genome,and dramatically increases genetic diversity.In recent years,researches have found that most CNVs are closely related to complex diseases.If a cancer gene is directly encompassed or overlapped by a CNV,it may lead to activation of oncogenes or inactivation of tumor suppressor genes,and finally results in tumorigenesis.CNVs can affect gene expression,phenotype differences and phenotypic adaptations by changing gene dosages and gene activities,and then sequentially lead to tumor or any other genetic dieases.Investigating CNVs is apparently helpful for studing chromosome recombination,genomic evolution,gene expression and the pathogenesis of multiple complex diseases especially tumor.

OBJECTIVE To explore the risk factors and protective measures on ICU attendants.METHODS According to the risk factors of ICU occupational exposure,we developed and standardized the implementation of the protective measures.RESULTS The occupational exposure protection awareness,prevention methods,and self-protection were improved.CONCLUSIONS The education about occupational of exposure can improve the management of occupational safety and ensure the protection of physical and mental health of attendants,and to prevent the occurrence of hospital infection.

Objective To introduce three-dimensional management mode to manage the devices in the operating room so as to reduce the risks.Methods A three-dimensional quality control group was established to strengthen the devices management.From three dimensions of thinking,communication and action some measures were proposed including training for standardized operation and incident treatment,improving guidance,sticking warning signs,advocating active report of adverse events,preventive maintenance and etc.Efficacy inspection and continuous improvement were carried out.Results The examination scores,inspection results and active reports of adverse events were significantly different before and after the introduction of three-dimensional management mode.Conclusion Three-dimensional management mode,in which the three dimensions connect to and cycle through each other,makes nursing staffs progressively develop the habit of safe operation in an environment of safety culture.Three-dimensional management mode is a scientific and applicable management method to reduce risks in using the devices in the operating room.

Objective To observe the characteristics of coronary hemodynamics in acute hibernating myocardium (AHM) model by intracoronary doppler guidewire. Methods 13 little domestic Chinese swine were established to the model of AHM by interventional method (closed chest),intracoronary Doppler guidewire were used to measure average peak velocity (APV),diastolic systolic velocity ratio (DSVR) and coronary flow velocity reserve (CFVR) distal to the stenosis in the period of pre model,post model and reperfusion.Then animals were executed,the histomography changes of AHM cells were observed.Results 10 animals (76 92%) were established to the model of AHM successfully,myocardium necrosis were not found under microscopical examination.APV and CFVR distal to the stenosis decreased significantly in AHM model ( P

Objective To study the preventive role of lysine, proline and calcium ascorbate on experimental osteoporosis in ovariectomized rats. Methods Ninety 6-9-month-old female rats were divided randomly into 9 groups: lysine hydrochloride low dose (LL) and high dose(LH) groups, proline low dose(PL) and high dose(PH) groups, calcium ascorbate low dose(CL) and high dose(CH) groups, calcium gluconate(CG) group, model(MOD) and SHAM groups. All groups except SHAM group were bilaterally ovariectomiged. At the 4 th, 8 th, and 12 th week, blood samples were collected for biochemical examination including the levels of ACP, ALP, Ca and P. Results Compared with SHAM and MOD groups, body weight of LL group increased most. Additionally, LL and LH promoted the activity of ACP and ALP〔(2.250?1.297)U/L and (300.3?136.9)U/L,P

Objective To investigate the effect of Mlot-4 cells onset with Roscovitine (ROSC)as some Cyclin-dependent kinases(CDK),inhibitor.Methods The logarithmic growth phase Molt-4 cells treated with ROSC at a final concentration ranging between 1～20 μmol/L and harvested in different time point,DNA assay of single cells by flow cytometry was used to detect the effect of cell cycle arrest and Annexin-V/FITC assay was used to detect the effect of cell apoptosis. Results It showed that ROSC exerted strong inhibitory effect on proliferation and cell cycle progression of Molt-4 Accumulation of G2/M arrested cells starting 6 h after onset of 10 μmol/L and 20 μmol/L ROSC;at the same time,the cell apoptosis of Molt-4 would be detected,According with the time and concentration changing,the cell apoptosis rate would rise.Conclusion It is concluded that Roscovitine(ROSC)as some Cyclin-dependent kinases(CDK),inhibitor,It has dual effects to Molt-4 cells,not only the effect of cell cycle arrest but also the effect of cell apoptosis.

Objective To observe the effects of DanShen on the growth of hepatocellular carcinoma in malignant obstructive jaundice in the SD rat model. Methods The model was established by vaccination of transplanting tumour in the porta hepatis with the walker-256 hepatocarcine line, and then obstruction was caused by the infiltration and metastasis of hepatocellular carcinoma. ② The SD rats were divided into four groups: the rats treated by 0.9% NS (n=12), the rats treated by Inosine + Vitamin C (n=20), the rats treated by DanShen (n=20) and the rats treated by 5-FU(n=20). ③ The liver function, morphological changes and the expression of PCNA VEGF and ICAM-1 in carcinoma and peri-carcinoma tissues, adjacent lobe (left-internal lobe) as well as lung tissues were observed after four experimental groups were successively treated by four medicines. ④ Statistical analysis was done to the experimental results. Results ① The growth of rats treated by DanShen injection showed that liver injury caused by malignant obstructive jaundice was significantly relieved compared with liver function and pathological morphological changes in other groups(P0.05); ③ The expression of PCNA VEGF and ICAM-1 in carcinoma, peri-carcinoma adjacent lobe (left-internal lobe) tissues as well as lung tissues were significantly downgraded in groups treated by DanShen injection compared with those in groups treated with 0.9%NS and Inosine combined with Vitamine C (P0.05). Conclusion DanShen injection not only has protective effects on liver injury caused by obstructive jaundice, but the medicine can inhibit the proliferation and growth of hepatocarcinoma, interfere with the vascularization of tumors, and prevent recurrence and metastasis of hepatocarcinoma.

Objective To investigate the role of estrogen in spontaneous repair of osteochondral defect,so as to provide guidance for the application of estrogen in tissue engineering.Methods Seventytwo healthy adult female SD rats (4-month-old) were assigned to negative control group (group A,n =24),ovariectomized group (group B,n =24) and ovariectomized + estrogen treatment group (group C,n =24) according to the random number table.Rats in group C were intraperitoneally injected 0.1 mg/kg estradiol benzoate once per week after operation.An osteochondral defect model (diameter:2 mm,height:1.5 mm) was established in femoral trochlea of rats 4 weeks after operation.At 2,10 and 20 weeks after the modeling,8 rats from each group were sacrificed.Femoral condyles were collected to measure bone volume fraction (BVF),number of bone trabeculae (Tb.N),trabecular thickness (Tb.Th) and trabecular spacing (Tb.Sp) in the osteochondral defect area by micro-CT scanning.Morphological changes were observed by HE staining,histomorphological changes and cartilage regeneration by safranine O-fast green staining,osteoclast count by tartrate-resistant acid phosphatase (TRAP) staining,distribution of matrix metalloproteinase-9 (MMP-9) by immunohistochemistry and expressions of osteoprotegerin (OPG),receptor activator of nuclear factor-κB ligand (RANKL) and MMP-9 by real-time-PCR.Results Compared to group B,increased BVF and Tb.N and decreased Tb.Sp were observed in groups A and C at each time point.More bone matrix formations were observed in groups A and C than in group B at 2 weeks,cysts (also known as cystic cavities) in regenerated subchondral bone and cracks in subchondral bone plate were observed in group B at 10 and 20 weeks,and proliferation of osteoclasts was active within lesions in group B at 10 and 20 weeks.Compared to group B,lowered levels of RANKL and MMP-9 (P ＜ 0.05) and significantly increased level of OPG (P ＜ 0.01) were observed in groups A and C at each time point,and osteoclast count in groups A and C was lowered at 10 and 20 weeks (P＜0.05).No regeneration of cartilage layer was observed in all groups.Conclusions Excessive proliferation of osteoclasts results in formation of cystic cavities and cracks.Estrogen improves the speed and quality of bone repair by regulating activities of osteoblasts and osteoclasts,so it can be used to treat osteochondral defect in tissue engineering.