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 investigate the method of anterior transsternal approach for the patients with upper thoracic spine diseases and the clinic results.[Method]Six cases upper thoracic spinal diseases,1 case of C7/T1 grade V dislocation,1 case of T1、2 TB,2 cases of upper thoracic tumor,1 case of T2 fracture and 1 case of T2、3 disc prolapse,were treated with the anterior transsternal approach operation since Oct.2001.The lesions areas were exposed via partial or complete sternotomy.The relative articles were reviewed.[Result]The average follow-up was 12.4 months(range from 6 to 22 months,except the died one).The case of C7/T1 grade V dislocation died of respiratory tract obstruction and one case of malignant schwannoma recurred 6 months post-operation.Good results were obtained in the other 4 cases.No operative complication happened in all cases.[Conclusion]While the transthoracic lateral approach cannot expose the upper thoracic spine clearly,the anterior cervical approach cannot expose the T2、3 clearly also.The anterior transsternal approach can provide a safe access to the lesions located on the upper thoracic spine above T4.

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 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.

Programmed death-ligand 1 (PD-L1 ),which is highly expressed in NSCLC,can be divided into two categories:membrane PD-L1 and soluble PD-L1 .PD-L1 participates in tumor immune escape through combining with its receptor.PD-L1 immune checkpoint inhibitors have entered the phase Ⅰ studies and showed a good application prospect.It is also found that the sensitivity of PD-L1 immune checkpoint inhibitors is strongly associated with the expression of PD-L1 in tumor.Therefore,PD-L1 can be used as a biomarker to pre-dict its curative effect.

Objective To establish a method for the determination of berberine hydrochloride in Huanglian Jiangtang Pill. Methods The sample was extracted with hydrochloric acid-methanol(1 ∶ 100). The chromatographic conditions were as follows:Diamonsil C18 chromatographic column(250 mm? 4.6 mm,5 ? m)with a mobile phase of acetonitrile-0.05 mol/L potassium dihydrogen phosphate(28 ∶ 72),the detection wavelength at 350 nm and the flow rate being 1.0 mL? min-1. Results A good linearity was obtained from 0.244 ? g to 2.928 ? g of berberine hydrochloride in Huanglian Jiangtang Pill(r=0.999 9,n=7).The average recovery was 99.07 % and RSD=1.30 %(n=6). Conclusion This method is simple,sensitive,specific and accurate for determination of berberine hydrochloride in Huanglian Jiangtang Pill.

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 changes of rat brain mitochondrial uncoupling protein (UCP) content and activity, and explore the effect of UCP on mitochondrial energy metabolism during hypoxia exposure. Methods Adult SD rats were set randomly into control and hypoxia group (n=8 in each group). The rats of hypoxia group were put into a hypobaric chamber simulating 5000-meter high altitude for 3 days (23 h/d). The brain mitochondria was isolated by centrifugation. Mitochondrial oxidative respiratory function was measured by Clark oxygen electrode. Mitochondrial membrane potential was detected by Rhodamine123 method. The content of adenine nucleotide pool (ATP, ADP, AMP) in mitochondria was measured by high performance liquid chromatography. UCP content and activity were detected by [~ 3 H]-GTP binding method. Results High altitude hypoxia resulted in significant increase of UCP activity and a 2.9-fold rise of UCP content of rats (P