Objective To investigate the efficacy and safety of crizotinib in patients with advanced anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC),and focuse on analysis of its prognostic factors.Methods Fifty patients with advanced (stage m B-Ⅳ) ALK-positive NSCLC confirmed by cytology or histology in Peking Union Medical Collage Hospital from January 2013 to September 2016 were collected.The relevant clinical imformation and treatment protocols were recorded.The efficacy and safety of crizotinib were followed up,and its prognostic factors were analyzed.Results At the end of follow-up,the median progression free survival (PFS) of progressed patients (n =24) was 9.6 months (95％ CI:8.3-10.9 months),of which five patients died.The median follow-up time of non-progressed patients (n =26) was 10.7 months.The most common adverse event was abnormal liver function (48.0％,24/50).In the single factor analysis of Kaplan-Meier,younger or equal to 40 years old patients had a longer PFS (P =0.017),and the COX regression analysis (Enter method) also had statistical significance differences (HR =6.1,95％ CI:1.4-27.5,P =0.018).However,gender (HR =0.8,95％ CI:0.2-2.6,P =0.697),smoking history (HR =1.5,95％ CI:0.4-5.6,P =0.524),pathology (HR =1.1,95％ CI:0.3-4.2,P =0.922),tumor stage (HR =1.7,95％ CI:0.4-8.4,P =0.502),epidermal growth factor receptor (EGFR) mutant type (HR =0.4,95％ CI:0.4-4.3,P =0.461),EGFR unknown (HR =1.3,95％ CI:0.3-6.1,P =0.727),Eastern Cooperative Oncology Group Performance Status (ECOG) PS score (HR =2.0,95％ CI:0.6-6.8,P =0.290),the status of previous treatment (HR =0.6,95％ CI:0.2-1.8,P =0.385) and brain metastasis (HR=0.7,95％CI:0.1-3.2,P=0.628) were not associated with disease progression Conclusion Crizotinib has good efficacy and is safe and well-tolerated to advanced ALK-positive NSCLC patients,and age is the independent prognostic factor.

Objective To detect the modification levels of H2AKll9 ubiquitination (H2AK119ub) and H2BK120ub,and to analyze the relationship between the levels of H2AK119ub,H2BK120ub and arsenic exposure.Methods A cross-sectional study was conducted in typical areas of drinking water type of endemic arsenicosis in Shanxi and Jilin provinces.Totally 281 residents who had drank local water for more 10 years were enrolled in this study,these participants were divided into control group (water arsenic content ＜ 0.01 mg/L),low arsenic exposure group (water arsenic content ranged 0.01-0.05 mg/L),medium arsenic exposure group (water arsenic content ranged ＞ 0.05-0.10 mg/L) and high arsenic exposure group (water arsenic content ＞ 0.10 mg/L).Among them,including 60 subjects in control group (20 males and 40 females),61 subjects in low arsenic exposure group (27 males and 34 females),50 subjects in medium arsenic exposure group (17 males and 33 females),and 110 subjects in high arsenic exposure group (40 males and 70 females).Drinking water and urine samples were collected and the arsenic content was detected by the method of atomic fluorescence spectrometry.After extracting leukocytes histone from the peripheral venous blood that collected from the subjects,the levels of H2AK119ub and H2BK120ub were detected by dot blotting.The levels of water arsenic,urinary arsenic,water arsenic accumulative intake,H2AK119ub and H2BK120ub were expressed as medium and quartile [M (P25,P75)].Results Age,body mass index (BMI),gender,smoking and alcohol drinking between control group and water arsenic exposure groups had no statistical differences (x2 =3.780,3.572,1.938,4.937,6.025,all P ＞ 0.05).Compared the contents of water arsenic [0.005 (0.003,0.006),0.024 (0.017,0.037),0.076 (0.057,0.084),0.150 (0.124,0.185) mg/L],the contents of urinary arsenic [0.011 (0.006,0.017),0.018 (0.004,0.072),0.061 (0.032,0.124),0.134 (0.069,0.223) mg/L],the water arsenic accumulative intake [0.342 (0.248,0.477),1.641 (1.012,2.324),5.273 (3.690,7.036),7.716 (5.608,12.053) mg] among the control,low,medium and high arsenic exposure groups,the differences were statistically significant (Hc =256.041,88.615,218.610,all P ＜ 0.01).Compared the levels of H2AK119ub [1.231 (0.856,1.817),1.244 (0.792,1.884),1.376 (0.743,1.981),1.390 (0.906,2.045)],H2BK120ub [0.350 (0.186,0.589),0.363 (0.152,0.678),0.428 (0.134,0.788),0.276 (0.146,0.453)] in human peripheral blood leukocytes among control,low,medium and high arsenic exposuregroups,the differences were not statistically significant (Hc =2.130,4.330,all P ＞ 0.05).There were no correlations between H2AK119ub and water arsenic content,water arsenic accumulative intake (r =0.104,-0.008,all P ＞ 0.05);there was a positive correlation between H2AK119ub and urinary arsenic content (r =0.166,P ＜ 0.05).There were negative correlations between H2BK120ub and water arsenic content,water arsenic accumulative intake (r =-0.183,-0.159,all P ＜ 0.05);there was no correlation between H2BK120ub and urinary arsenic content (r =-0.101,P ＞ 0.05).There was a negative correlation between H2AK119ub and H2BK120ub (r =-0.127,P ＜ 0.05).Conclusion External exposure to arsenic may change the levels of H2BK120ub in human peripheral blood leukocytes.

Nowadays, lung cancer is the malignant tumor of the highest morbidity and mortality over the world, and non-small cell lung cancer (NSCLC) makes up about 80%. hTere is a great many NSCLC patients have been in advanced stage when diagnosed. As a result, people pay more attention to curing advanced NSCLC. hTe standard treatment to advanced NSCLC is platinum-based combined chemotherapy. However, chemotherapy drugs usually have limited effects on improving the survival of the patients. hTen exploring new therapies is extremely urgent to us. Now, molecular targeted therapy has been the most promising research area for the treatment of NSCLC with researches going deep into pathogenesis and biological behavior of lung cancer. Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) have achieved a great suc-cess in the treatment of advanced NSCLC. hTeir representatives are erlotinib and geiftinib. hTe two drugs have been widely used to treat advanced NSCLCs worldwide, especially for the patients with EGFR activating mutations. However, atfer a period of treatment (median time is 6 to 12 months), most patients will develop drug resistance to EGFR-TKIs. Intense research in these NSCLCs has identiifed two major mechanisms of resistance to TKIs:primary and acquired resistances. hTe research about resistance mechanism of NSCLC to EGFR-TKIs is a hot one because of their excellent effects on improving overall and progression-free survival. hTe aim of this article was to summarize the development of the resistance mechanisms.

Background and objective Small cell lung cancer (SCLC) is the most malignant neuroendocrine tu-mor and sensitive to chemotherapy and radiotherapy. However, most patients who receive ifrst-line chemotherapy will relapse within one to two years. Once recurrent, it indicates poor prognosis. Currently, the standard ifrst-line chemotherapy regimen of extensive-stage SCLC is platinum combined etoposide regimen while the standard second-line chemotherapy regimen is open to debate. hTe aim of this study is to analysis the prognostic factors of second-line chemotherapy in extensive-stage SCLC and to compare the differences of objective response rate, side effects and survival among different second-line chemotherapy regimens. Methods 181 patients who were diagnosed as extensive-stage SCLC and received second-line chemotherapy were collected.χ2 test was used to analysis the differences of enumeration data and between different groups. Kaplan-Meier method was used to calculate the overall survival (OS) and progression-free survival (PFS). Univariate analysis and Cox regression analysis were used to detect the prognostic factors. Objective response rate was evaluated by RECIST criteria and side effects were evaluated by WHO criteria. Results hTe patients who received second-line chemotherapy can be divided into 6 groups, namly group A (CE/EP regimen) 27 cases, group B (regimens containing TPT) 44 cases, group C (regimens containing CPT-11) 33 cases, group D (regimens containing TAX/DXL) 20 cases, group E (regimens containing IFO) 28 cases and group F (other regimens) 29 cases. hTe median OS in second-line chemotherapy as 7.0 months and was relevant with smoking his-tory (P=0.004), ECOG PS (P<0.001), liver metastasis (P=0.019) and bone metastasis (P=0.028) independently. hTe median PFS in second-line chemotherapy as 3.0 months and was relevant with smoking history (P=0.034), ECOG PS (P=0.011) and bone metastasis (P=0.005). hTe response rate among six regimens was signiifcantly different (P=0.017);hTere was not statistical signiifcance between each group. As to side effects, the incidence of gastrointestinal reaction in group C was higher than any other group. hTe differences of OS and PFS between six regimens in second-line therapy were not statistically differ-ent (P=0.914, P=0.293). Conclusion hTe most signiifcant prognostic factor of extensive-stage small cell lung cancer patients who received second-line chemotherapy was ECOG PS. hTe most optimal second-line chemotherapy regimen with deifnite curatice effect was controversial.

Background and objective At present, surgery is advocated for stage IIIa non-small cell lung cancer (NSCLC), and the survival of them is determined by many factors. hTe aim of this study is to analyze the inlfuencing factors of prognosis for stage IIIa surgical patients. Methods Between March 2002 and October 2012, 151 surgical cases that have postoperative pathological ifnding of stage IIIa NSCLC with completed followed-up data were received in the Peking Union Medical College Hospital. According to different N stages, 151 patients were divided into T4N0/T3-4N1M0 and T1-3N2M0 stages. Kaplan-Meier survival method was used to calculate the overall survival (OS) and progression-free survival (PFS), and to proceed univariate analysis of survival. Cox regression analysis was used to conduct multivariate analysis. A p-value less than 0.05 was evaluated as statistically signiifcant. Results 151 stage IIIa NSCLC patients had 43 stage T4N0/T3-4N1M0 cases and 108 stage T1-3N2M0 cases. hTe median OS and PFS of the whole group were 38.9 and 12.9 months respectively. hTe median OS of stage T4N0/T3-4N1M0 and T1-3N2M0 were 48.7 and 38.9 months. hTe median PFS of them were 14.9 and 19.8 months respectively. hTere were no signiifcant differences of OS and PFS between two groups. Univariate and multivari-ate analysis indicated that postoperative chemotherapy had a signiifcant inlfuence on OS of the surgical patients with stage IIIa NSCLC (P=0.001), and family history of tumor had a signiifcant inlfuence on PFS (P<0.05). hTe maximum diameter of tumor had a signiifcant inlfuence on PFS only in univariate analysis. Conclusion For stage IIIa NSCLC, postoperative chemotherapy can increase OS and PFS, but postoperative radiotherapy have no beneift on them.

Background and objective Nowadays, comprehensive treatment, including surgery, chemotherapy and radiotherapy is advocated for stage III non-small cell lung cancer (NSCLC). However, many researchers have questioned the effectiveness of surgery. The aim of this study is to evaluate the effect of surgery for stage III NSCLC. Methods Between March 2002 and October 2012, 310 cases that have completed followed-up data with stage III NSCLC were received in the Peking Union Medical College Hospital. They were divided into surgical and non-surgical groups according to whether received surgery when diagnosed. In TNM staging, stage III NSCLC includes stage IIIa and IIIb, and stage IIIa NSCLC can be grouped into stage T4N0/T3-4N1M0 and T1-3N2M0 according to different N stages. Analyzed the enumeration data by Chi-Square test. Kaplan-Meier survival method was used to calculate the overall survival (OS) and progression-free survival (PFS), and to draw the survival curves. AP value less than 0.05 was evaluated as statistically significant. Results Three hundred and ten stage III NSCLC patients include surgical group 189 cases and non-surgical group 121 cases. One hundred and eighty-eight stage IIIa NSCLC patients include surgical group 152 cases and non-surgical group 36 cases. In stage IIIa, stage T4N0/T3-4N1M0 had 57 patients with 44 surgical and 13 non-surgical patients, and stage T1-3N2M0 had 131 patients with 108 surgical and 23 non-surgical patients. Thirty-seven out of 121 stage IIIb NSCLC patients received surgery. They had 22 stage T4N2M0 cases and 15 stage T1-4N3M0 cases. The patient whose performance status was 0 and staging was stage IIIa was more inclined to undergo surgery. For stage IIIa NSCLC patients, the median OS of surgical and non-surgical groups were 38.9 and 21.8 months, and the median PFS of them were 19.2 and 11.9 months respectively. The difference of OS between the two groups was significant (P=0.041), but the PFS of them had no significant difference (P=0.209). For stage T4N0/T3-4N1M0 which belongs to stage IIIa, the median OS of surgical and non-surgical groups were 48.7 and 20.1 months, and the median PFS of them were 14.6 and 10.5 months respectively. There were no significant differences of OS and PFS between the two groups (P>0.05). For stage T1-3N2M0 which also belongs to stage IIIa, the median OS of surgical and non-surgical groups were 38.9 and 30.8 months, and the median PFS of them were 19.8 and 12.7 months respectively. There were also no significant differences of OS and PFS between the two groups (P>0.05). The maximum diameter of tumor and auxillary chemotherapy had significant influences on OS and PFS of stage IIIa-N2 NSCLC patients, while the histology of tumor only influenced the OS of them (P<0.05). Conclusion The patient whose performance status is 0 and staging is stage IIIa is more inclined to undergo surgery. Surgery can prolong OS of patients with stage IIIa, especially for stage T4N0/T3-4N1M0. However, it has no benefit on PFS. The maximum diameter of tumor and auxillary chemotherapy have significant influences on OS and PFS of stage IIIa-N2 NSCLC patients, while the histology of tumor only influence the OS of them.

Background and objective Small cell lung cancer (SCLC) is the most malignant neuroendocrine tumor but highly sensitive to chemotherapy and radiotherapy. At present, the standard ifrst-line chemotherapy regimen of extensive-stage SCLC is platinum combined etoposide regimen. However, most patients who receive ifrst-line chemotherapy will relapse within one to two years. Once recurrent, it indicates poor prognosis. In this study, we analyzed the survival among all extensive-stage SCLC and patients who received ifrst-line chemotherapy and determined prognostic factors. Methods Total of 394 patients who were diagnosed as extensive-stage small cell lung cancer from February 2001to December 2011hospitalized in Peking Union Medical College Hospital were collected. Kaplan-Meier method was used to calculate the overall survival (OS) and progression-free survival (PFS). Univariate analysis and Cox regression analysis were used to detect the inlfuence factors of survival. Results hTe median OS of all extensive-stage small cell lung cancer was14.8 months;1-year, 2-year and 5-year survival rates were 58.9%, 27.2%and 7.8%, respectively. According to the results of univariate and Cox multivariate analysis, OS of extensive-stage SCLC was closely associated with age (P=0.006), ECOG PS (P=0.021), liver metastasis (P<0.001), bone metastasis (P<0.001) and chemotherapy (P<0.001). hTe mortality risk of patients who didn’t receive chemotherapy was 4.919 times higher than that who received;the mortality risk of patients without liver, bone metastasis was reduced by approximately 50 percent. hTe ifrst-line chemotherapy was mainly EP (DDP+VP-16) or CE (CBP+VP-16) regimens (accounting for 82.8%) with 4-6 cycles. hTe median OS and PFS in ifrst-line chemotherapy were15.1months and 7.5 months, respectively. hTe result of Cox regression analysis indicated that OS in ifrst-line chemotherapy was remarkably related to smoking history (P=0.041), liver metastasis (P<0.001), bone metastasis (P<0.001), chemotherapy cycle number (P<0.001);PFS was relevant with smoking history (P=0.003), liver metastasis (P=0.001), bone metastasis (P<0.001), chemotherapy cycle number (P<0.001). hToracic radiotherapy was not an independent inlfuence factor of OS and PFS in extensive-stage small cell lung cancer. Con-clusion hTe patients who were younger than 60-year old, with good KPS, absence of liver and bone metastasis had better prognosis. Patients should receive chemotherapy with ifrst-line standard regimen (CE/EP regimen). It was beneifcial to sur-vival if the effect of ifrst-line chemotherapy was SD or PR-CR and the proper chemotherapy cycle number was 4-6 cycles. hTe role of thoracic radiotherapy in extensive-stage small cell lung cancer needed to be investigated further.

Objective To discuss the correlation between the nurse′s humanistic care quality and the core competence of the low seniority nurses.Methods A total of 262 low seniority (work ≤3 years)registered nurses were selected from our hospital and completed the general information scale,nurse′s humanistic care quality scale and nurse′s core competence scale.Results The total score of humanistic caring quality of nurses was (1 1 0.41 ±1 1 .1 1 ).The total score of nurse′s core ability was (1 49.1 6 ±31 .08).Their total score and attributes were in the positive correlation (r =0.1 22-0.393,P <0.05).Conclusions Nurse′s humanistic care quality has the obvious correlation with the nurse′s core competence.When the hospital managers build up the humanistic care quality in the low seniority of nurses,it should carry on the care education,clear the care practicing and the standard of manage,improve the total level of the nurse′s humanistic care quality,training and develop the nurse′s core competence constantly in order to promote the total level nursing work.

Objective To investigate the relationship between single nucleotide polymorphism(SNP)of the peroxisome proliferator activated receptor γ (PPARγ) gene Rs1801282 and brick-tea type fluorosis. Methods From 2012 to 2013, this cross-sectional study was performed in 16 endemic fluorosis areas of brick-tea type in Inner Mongolia Autonomous Region,Qinghai and Xinjiang Uygur Autonomous Region of China,to select adults>18 years old as subjects, who were diagnosed as skeletal fluorosis by X-ray. All of the subjects filled in demography survey questionnaire; the survey contents included general characteristic s, and average daily brick tea intake. Drinking tea samples and urine samples of each subject were collected, and fluoride content of urine and brick-tea was determined via the ion selective electrode method (WS/T 89-2006). X-ray scintigraphy was used to diagnose skeletal fluorosis, according to the "Diagnostic Criteria of Endemic Skeletal Fluorosis" (WS/T 192-2007); the subjects were divided into skeletal fluorosis group (case group) and non-skeletal fluorosis group (control group). To collect venous blood 5 ml, whole blood DNA was extracted, and polymorphism at Rs1801282 of PPARγ was detected by MassARRAY time-of-flight mass spectrometry, to calculate odds ratio (OR) and 95% confidence interval (CI). Results There were 1 414 people included in this study,including 347 in case group and 1 067 in control group. By the Hardy-Weinberg balance test, the PPARγ gene Rs1801282 genotype was representative in case group, control group and each nationality (P > 0.05). The difference of PPARγ gene Rs1801282 genotype in case group and control group was not statistically significant (OR was 0.991, 95%CI: 0.704 - 1.395, the adjusted OR was 1.026, 95%CI: 0.707-1.489).The difference of PPARγ gene Rs1801282 genotype(CC,CG+GG)in case group and control group in different nationality was not statistically significant (Tibetan: OR was 1.400, 95%CI: 0.576 - 3.404, the adjusted OR was 1.258, 95%CI: 0.474 - 3.340; Kazak: OR was 0.898, 95%CI:0.516 -1.562,the adjusted OR was 0.936,95%CI:0.532 -1.648;Mongolia: OR was 1.148,95%CI:0.508-2.594, the adjusted OR was 1.644, 95%CI: 0.683 - 3.956; Han: OR was 1.058, 95%CI: 0.451 - 2.482, the adjusted OR was 0.959, 95%CI: 0.388 - 2.371; Russian: OR was 0.000, 95%CI: 0.000 - 0.000, the adjusted OR was 0.000, 95% CI: 0.000 - 0.000) with binary Logistic regression analysis. Conclusion We have found no association between SNP of PPARγ gene Rs1801282 and skeletal fluorosis of brick-tea type fluorosis in China.

Objective To study the urinary arsenic safety guideline value of a population for evaluating the arsenic exposure level in a certain population and providing evidence for the implementation of prevention and control measures in endemic arsenicosis area.Methods According to the data from the national high-arsenic drinking water sources screening in endemic arsenicosis area of drinking water type and quality supervision and inspection for water-improving project to decrease arsenic from 2005 to 2014,census data on arsenic poisoning in endemic arsenicosis area,data on surveillance of endemic arsenicosis,10 722 people with detailed personal information,complete water arsenic exposure data and accurate urinary arsenic detection data were selected to be the research objects.The relationship between urinary arsenic and water arsenic was analyzed based on the surveillance data of 4 501 people from 2013 to 2014.The safety guidance value of urinary arsenic was determined based on the geometric mean value of urinary arsenic in people exposed to water arsenic in the range of (0.050 ± 0.005) mg/L,and verified using the data of 6 221 people from 2005 to 2012.Every time,a random sample of 2 000 people was taken as the verification sample,the sensitivity and specificity of the index for determining whether water arsenic exposure exceeded the standard were determined by area under the ROC curve (AUC),and a total of 10 sample tests was performed.Results When the water arsenic concentration was less than 0.01 mg/L,the correlation coefficient of water arsenic concentration with urinary arsenic concentration was 0.097 (P ＜ 0.01);when the water arsenic concentration was more than 0.01 mg/L and less than 0.05 mg/L,the correlation coefficient of arsenic concentration with water arsenic concentration was 0.456 (P ＜ 0.01);when the water arsenic concentration was more than 0.05 mg/L,the correlation coefficient of water arsenic concentration with urinary arsenic concentration was 0.630 (P ＜ 0.01).With increase of water arsenic concentration,the concentration of urinary arsenic increased significantly,and the difference was statistically significant (x2 =2 337.956,P ＜ 0.01).When water arsenic concentration was in the range of (0.050 ± 0.005) mg/L,the urinary arsenic geometric mean was 0.032 mg/L.AUC analysis of 10 random samples of 2 000 people showed that the geometric mean of urinary arsenic was 0.032 mg/L in the population,which can accurately distinguish whether the water arsenic level exceeded 0.05 mg/L,and the AUC value was higher than 0.94.And the sensitivity and specificity were achieved 0.898 and 0.844.Conclusions The geometric mean of urinary arsenic is 0.032 mg/L,which can be used as a safety guideline value for urinary arsenic in the population.When the geometric mean of urinary arsenic exceeds this value,the population may be exposed to high arsenic.