Crizotinib is a tyrosine kinase inhibitor (TKI),which is a target for echinoderm microtubule associated protein like 4-anaplastic lymphoma kinase (EML4-ALK).It can prolong the progression free survival (PFS)of ALK positive patients with advanced non-small cell lung cancer (NSCLC).The median PFS in the first-line and second-line mPFS is 10.9 months and 7.7 months.However,despite an initial benefit,patients inevitably experience tumor progression,due to the ALK fusion gene amplification and secondary mutations of ALK kinase domain.Clinical trials show the promising efficacy like next generation ALK inhibitors and heat shock protein 90 (HSP90)can overcome acquired resistance.

Objective To observe EML4-ALK fusion gene mutation expression rate in serum and cancer tissue of patients with non-small cell lung cancer (NSCLC) in Chinese populations,and the consistency of mutation in serum and cancer tissues,and the feasibility of real-time,dynamic detection of EML4-ALK fusion gene therapy by using FQ-PCR.Methods 123 cases of serum and 98 cases of tissue of NSCLC patients were detected by fluorescence quantitative polymerase chain reaction,and 77 cases of which were matched.The clinical curative effects of ALK inhibitor (crizotinib) were analyzed.Results 13 rearrangement in 123 (10.6％) of the patients'serum samples and 11 rearrangement in 98 (11.2％) tumor tissue.EML4-ALK rearrangement were mainly discovered in adenocarcinoma (x2 =4.083,P =0.036),and non-smokers in NSCLC (x2 =5.326,P =0.019).The consistency of patients with EML4-ALK matched tumor tissue and serum reached 66.7％ (6/9,κ =0.779).The EML4-ALK fusion gene rearrangement in patients receiving ALK inhibitor (crizotinib) treatment achieved significant benefit.Conclusion The EML4-ALK rearrangement mainly exists in the serum and tumor tissue of adenocarcinoma and non-smokers in NSCLC.When tumor tissue samples are unable to be obtained,FQ-PCR can be used to detect serum EML4-ALK fusion gene mutation for selecting NSCLC patients suitable for crizotinib therapy instead of tumor tissue.

Objective To examine the positive rate of c-MET gene amplification in primary and lymph node-metastatic non-small cell lung cancer( NSCLC),and to explore their relationships. Methods From November 2011 to November 2013,147 cases of primary NSCLC consisting of 71 cases of paired lymph node-metastatic tumors and 47 cases of normal lung specimens as the control group were collected in General Hospital of Beijing Military Region. The c-MET gene copy number was examined by RT-PCR and the positive rate of c-MET gene amplification among NSCLC population was figured out,thus the consistency of c-MET gene ampli-fication in advanced primary NSCLC and associated lymph node-metastases and the relationship between c-MET gene amplification and clinical data were analyzed. Results The positive rate of c-MET gene amplification on primary tumor was 8. 84% (13 / 147). For those 71 paired cases,the positive rate on primary tumor was 8. 45%(6 / 71),with that of lymph node-metastases 18. 31%(13 / 71). Among the 71 cases,there were 8 cases whose metastases were positive but primary tumors negative and 1 case whose primary tumor was positive but metastases negative. It was of statistical significance between the two groups(McNemar test,χ2 = 4. 274, P = 0. 039). The positive rate of primary tumors could be predicted by lymph node-metastases(κ = 0. 464, P ﹤ 0. 001). The sensitivity was 83. 3% and the specificity was 87. 7% . Positive rate of c-MET amplification was higher in male and smoking patients with lymph node-metastases above N2 . Conclusion c-MET amplifica-tion test should be one of the routine genetic testing projects. The amplification on primary tumors is higher than that on lymph node-metastases,implying that metastases test can pick out more patients with indication. Metas-tases test can predict the amplification on primary focus,and it is an alternative way to guide the treatment of c-MET target medicine. Moreover,the clinical characteristic can be served as an indicator of positive c-MET am-plification.

Objective To investigate the expression and significance of intermedin (IMD) and its.receptors CRLR,RAMP1,RAMP2 and RAMP3 in cancer tissues of patients with non-small cell lung cancer.Methods The mRNA gene expressions of IMD,CRLR,RAMP1,RAMP2 and RAMP3 were detected by realtime quantitative RT-PCR in cancerous and para-cancerous tissues from 27 patients with lung cancer.Results Real-time quantitative PCR detection results showed that the expression of IMD,CRLR,RAMP1,RAMP2 and RAMP3 in cancer tissues were [(59±7.9)×10-8,(96±2.7)×10-6,(29±3.9)×10-9,(14±2.6)×10-6,(65±1.1)×10-6]which were higher than those in adjacent tissues[(40±4.7)×10-10,(21 ±3.9)×10-6,(53±7.8)×10-10,(64±1.9)×10-8,(36±1.3)×10-9] to some extent (all P ＜ 0.05); the higher expression of RAMP3 was found is higher expressions than RAMP1 and RAMP2 in cancer tissues (all P ＜ 0.05).Conclusion The expressions of IMD and its receptors in cancer tissues are higher than those in paracancerous tissues.IMD may play an important role in the development of cancer by activate RAMP3 which is the most high expressed receptor in cancer tissues.Therefore,it might be helpful for the investigation of new gene thereapy in non-small cell lung cancer.

Her-2( human epidermal growth fact or receptor 2) is a type of 185 kD across the membrane glycoprotein with tyrosine kinase activity,play an important function in the cell divisions across a cell membrane proliferation signal transduction,and finally affect biological activities of tumor cells from multiple ways,such as a tumor cell proliferation and adhesion,transfer and differentiation and other related gene regulation.Recent studies show that Her-2 overexpression rate of gastric cancer patients is about 12％ ～ 35％,and Her-2 is a gastric cancer poor-prognostic factors,while Her-2 monoclonal antibody-Trastuzumab is expected to become a new standard gastric cancer treatment for the patients with Her-2 overexpressed.

Objective To investigate the expression of intermedin (IMD) in plasma and tissues of lung cancer patients compared with control group and to explore the relationship of IMD with the stage and pathological type of lung cancer. Methods The content of IMD in plasma of 88 lung cancer patients measured using ELISA, 36 lung cancer tissue using immunohistochemistry, compared with control groups. Results Healthy control group IMD level [(38.68±12.65) pg/ml] was lower than lung cancer group [(81.61 ± 30.78) pg/ml] (t =-5.818, P <0.05); There was no significant difference of IMD between small cell [(68.61 ± 30.01) pg/ml] and non-small cell lung cancer [(75.51 ±32.74) pg/ml] (t =-0.680, P >0.05); IMD in stage Ⅳ is higher than stage Ⅰ - Ⅲ (t =-3.444, -3.093, -3.955, P <0.05); IMD with distant metastasis is significantly higher than that without distant metastasis (t =8.052, P =0.000). IMD expression in lung cancer tissues [23/36 (63.9 %)] is significantly higher than adjacent tumor tissues [5/21 (23.8 %)] (x2= 8.525, P <0.05). IMD in Stage Ⅲ[14/17(82.4 %)] is significantly higher than in stage Ⅰ [1/5 (20.0 %)] (x2 = 6.924, P =0.009). Conclusion The expression of IMD in lung cancer patients is significantly higher than control groups. Expression has correlation with stage and metastasis, which might play a vital role in the pathogenesis of lung cancer.

Objective To study the correlated mechanisms and clinical effect of hidden hemorrhage after total hip arthroplasty (THA) and total knee arthroplasty(TKA). Methods From March 2001 to May 2005, 61 patients were treated with THA and 73 patients were treated with TKA. The patients treated with THA involved 22 males and 39 females with an average age of 68 years(range 61-79 years). The patients treated with TKA involved 23 males and 50 females with an average age of 73 years(range 65-77 years). All arthroplasties were primary and unilateral, and the 24 h fluid resuscitation was not more than 2000 ml. Using Gross formula, the true total blood loss was calculated depending on height, weight and pre- and post-operation Hct, and the hidden hemorrhage was got by subtracting the visible blood loss from total loss. Results Following THA, the mean total loss was 1520 ml and the hidden hemorrhage 482 ml(32%). Following TKA, the mean total loss was 1508 ml and the hidden hemorrhage was 776 ml(52%). The difference of hidden hemorrhage between THA and TKA was significan different(P

Objective To study the release of synthetic gene expression induced by vasopressin Ⅱ (U Ⅱ ) in hypoxic pulmonary hypertension. Methods Rat model of HPH was establish. RIA was used to observe the different time points of hypoxia in plasma and the dynamic changes of U Ⅱ , ADM content in bronchoalveolar lavage fluid (BALF). The impact of the release of U Ⅱ , as well as the relation-ship among U Ⅱ , ADM and HPH were explored to reveal the role of U Ⅱ in the pathophysiology of HPH. Results Rat HPH model was successfully established. Hypoxia promoted the expression, synthesis and release of U Ⅱ in lung tissue. U Ⅱ involved in the pathogenesis of HPH. HPH took place in the development of U Ⅱand was positive correlated with ADM. Conclusion The two peptides have opposite physiological effects on blood vessel, which suggest that these two peptides play an important role in maintaining the balance between the pul-monary circulation and lung ventilation as well as the stability of pulmonary artery pressure.

A model of hypoxic pulmonary hypertension (HPH) was reproduced in rats by exposing them to chronic hypoxia environment corresponding to 5km level. At 10d,20d, 30d after hypoxia in hypoxia groups and control group, the pulmonary vascular structural changes were observed with optical microscope, histochemistry and electronic microscope. The changes in hypoxia groups were as follows: ①the wall of small pulmonary arteries of every calibre showed marked thickening compared with that in control group, and the main changes involved smooth muscle cells(SMC)proliferation and collagen deposition in the vessels wall; ② SMC proliferation, muscularization of non myocytic arteries and partial myocytic arteries were observed in intra acinar pulmonary arteries, so the counts of muscular arteries significantly increased compared with control group( P

Objective To observe the dynamic changes of urotensionⅡ (U Ⅱ) content in plasma and bronchoalveolar lavage fluid (BALF) of rats with chronic hypoxic pulmonary hypertension and to investigate the effects of hypoxia on the synthesis and secretion of U Ⅱ and the correlation of U Ⅱ with the mean pulmonary artery pressure (mPAP) and the partial pressure of arterial oxygen (PaO 2). Methods Male Wistar rats were randomly divided into control group and hypoxic groups. Model of chronic hypoxic pulmonary hypertension was established by normal barometric and discontinuous hypoxia. mPAP and RVdp/dt max of each rat were measured using right cardiac catheterization. PaO 2 was detected by blood gas analysis. U Ⅱcontents in plasma and BALF were detected by radioimmunoassay. Results During hypoxia, mPAP, RVdp/dt max , U Ⅱ content in plasma, and BALF increased in rats (P