Objective:To explore the expressions of calcium-activated chloride channel protein 1(ANO1)and E-cadherin in colorectal cancer(CRC)tissue and their relationships with the clinicopathological characteristics of the CRC patients,and to clarify their clinical significances.Methods:The surgical tissue specimens from 77 patients with primary CRC were collected.Immunohistochemistry(IHC)method was used to detect the protein expressions of ANO1 and E-cadherin in CRC tissue;Spearman correlation analysis method was used to analyze the correlation between their expressions;PCR fluorescence probe method was used to detect the KRAS/NRAS mutations in CRC tissue;chi-square test or Fisher's exact probability method was used to analyze the relationships between the expressions of ANO1 and E-cadherin and clinicopathological characteristics of the CRC patients.Results:The IHC results showed that the positive expression rate of ANO1 in CRC tissue was 24.7％,and the positive expression rate of E-cadherin was 63.6％.The Spearman analysis results showed that the expressions of ANO1 and E-cadherin in CRC tissue were positively correlated(r=0.458,P<0.05).Compared with the patients with tumor located in rectum,the positive expression rate of ANO1 in cancer tissue of the CRC patients with tumor located in colon was significantly increased(χ2=5.499,P=0.019);compared with the patients with TNM stageⅢ-Ⅳ,the positive expression rate of ANO1 in cancer tissue of the CRC patients with TNM stageⅠ-Ⅱ was significantly increased(χ2=4.774,P=0.029);compared with the patients with lymphnode metastasis,the positive expression rate of ANO1 in the CRC patients without lymphnode metastasis was significantly increased(P=0.034).Compared with the CRC patients with T4 stage,the positive expression rate of E-cadherin in the CRC patients with T1-T3 stage was significantly increased(P=0.024).Compared with the CRC patients with p53 positive,Ki-67≥90％,PMS2 positive and KRAS wild-type,the positive expression rate of ANO1 in cancer tissue of the CRC patients with p53 negative,Ki-67<90％,PMS2 negative and KRAS mutant was significantly increased(P=0.031,P=0.036,P=0.048,P=0.028).Conclusion:The expressions of ANO1 and E-cadherin in primary CRC tissue of the patients are positively correlated;ANO1 and E-cadherin are associated with multiple clinicopathological characteristics of the patients;ANO1 and E-cadherin may be involved in the occurrence and progression of CRC.

Objective To explore the value of KRAS mutation predicting prognosis of patients with colorectal liver-only metastasis after hepatectomy.Methods The retrospective case-control study was conducted.The clinicopathological data of 79 patients with colorectal liver-only metastasis who underwent hepatectomy in the Sun Yat-sen University Cancer Center between October 2010 and October 2016 were collected.KRAS mutation in colorectal cancer tissue was detected by fluorescent quantitative polymerase chain reaction (PCR) and laser flight mass spectrometer.Observation indicators:(1) KRAS mutation;(2) relationship between KRAS mutation and clinicopathological factors of patients with colorectal liver-only metastasis;(3) follow-up and survival situations.Follow-up using outpatient examination and telephone interview was performed to detect recurrence-free survival and overall survival up to June 30,2017.The relationship between KRAS mutation and clinicopathological factors of patients with colorectal liver-only metastasis was analyzed by the chi-square test or Fisher exact probability.The survival curve and time were respectively drawn and calculated by the Kaplan-Meier method,and COX regression model was used for survival analysis.Results (1) KRAS mutation:79 patients received KRAS gene detection of surgical tumor tissues,including 54 in wide-type mutation and 25 in mutant-type mutation.Of 25 patients in mutant-type mutation,mutation at codon 12 of KRAS exon 2 was in 21 patients,and GGT＞GAT (G12D),GGT＞GTT (G12V),GGT＞TGT (G12C),GGT＞GCT (G12A) and GGT＞CGT (G12R) of mutation types were respectively detected in 13,4,2,1 and 1 patients;mutation at codon 13 of KRAS exon 2 was in 3 patients,with a mutation type of GGC＞GAC (G13D);mutation at codon 61 of KRAS exon 3 was in 1 patient,with a mutation type of CAA＞CAT (Q61H).(2) Relationship between KRAS mutation and clinicopathological factors of patients with colorectal liver-only metastasis:primary tumor located in right and left hemicolon were detected in 11,14 patients with mutant-type mutation and 7,47 patients with wide-type mutation,respectively,with a statistically significant difference (x2=9.357,P＜0.05).(3) Follow-up and survival situations:79 patients were followed up for 2.0-71.0 months,with a median time of 29.0 months.Median recurrence-free survival time and median overall survival time were respectively 11.3 months,43.5 months in patients with mutant-type mutation and 9.9 months,44.3 months in patients with wide-type mutation,respectively,with no statistically significant difference in recurrence-free and overall survivals [hazard ratio (HR)=1.255,1.108,95％ confidence interval (CI):0.741-2.126,0.521-2.355,P＞0.05].Further analysis:of patients with low clinical risk score (CRS) of Memorial Sloan Caitlin Cancer Center (MSKCC),median recurrence-free survival time was 11.3 months in 17 patients with mutant-type mutation and 23.5 months in 26 patients with wide-type mutation,with a statistically significant difference in recurrence-free survival of patients (HR=2.082,95％CI:1.006-4.307,P＜0.05).The median overall survival time was 44.6 months in 17 patients with mutant-type mutation and 49.0 months in 26 patients with wide-type mutation,with no statistically significant difference in overall survival of patients (HR =1.165,95％CI:0.413-3.282,P＞0.05).Of patients with high CRS of MSKCC,median recurrence-free survival time and median overall survival time were respectively 5.6 months,28.7 months in 7 patients with mutant-type mutation and 4.5 months,36.7 months in 24 patients with wide-type mutation,with no statistically significant difference in recurrence-free and overall survivals (HR=0.402,1.197,95％CI:0.284-1.656,0.371-3.866,P＞0.05).Conclusions KRAS mutation is often detected in patients with right colon cancer.Recurrence-free survival time is obviously reduced in patients with KRAS mutation and low CRS of MSKCC.

OBJECTIVEWuji pill is a prescription of traditional Chinese medicine(TCM) and was composed of Rhizoma Coptidis, Fructus Evodiae Rutaecarpae and Radix Paeoniae Alba. The aim of this research is to investigate the effects of Wuji pill compound with different compatibility on the levels of enzymic activity of cytochrome P450 CYP3A1/3A2 in rat liver microsomes in vitro, and to confirm the compatibility mechanism of Wuji pill from the point of relationships between compound prescription of TCM and metabolism.

METHODWith testosterone being a probe, the levels of enzymic activity of CYP3A1/3A2 were detected by HPLC, which were suppressed by Wuji pill with different compatibility in vitro.

RESULTThe IC50 of Rhizoma Coptidis, Fructus Evodiae Rutaecarpae, Radix Paeoniae Alba and 1"-9" of different level Wuji pill is: 38.96, 871.96, 15 519.17, 43.17, 60. 47, 276.12, 133.40, 118.08, 88. 47, 64. 36, 35. 13 and 39. 91 mg x L -', respectively. Rhizoma Coptidis and 1-9" of Wuji pill can suppress the enzymic activity of CYP3A1/3A2 significantly, and the capability of Rhizoma Coptidis in Wuji pill of action on CYP3A1/3A2 can be modified by different composition of Fructus Evodiae Rutaecarpae and Radix Paeoniae in Wuji pill, and there are statistical differences among the IC50 of 1#-9# of Wuji pill. While the ratio of Rhizoma Coptidis raises up in Wuji pill, Wuji pill may suppress the enzymic activity of CYP1A2 largely.

CONCLUSIONThe reason why Wuji pill with different compatibility has different pharmacodynamics and pharmacokinetics characteristics is likely to lie in the difference of the capability of Wuji pill with different compatibility on CYP3A1/3A2. [Key words] Wuji pill; CYP3A1/3A2; testosterone; HPLC; different compatibility prescription of traditional Chinese medi-cine

Animals ; Aryl Hydrocarbon Hydroxylases ; antagonists & inhibitors ; metabolism ; Coptis ; chemistry ; Cytochrome P-450 CYP3A ; Drug Compounding ; Drugs, Chinese Herbal ; adverse effects ; pharmacology ; Enzyme Inhibitors ; adverse effects ; pharmacology ; Evodia ; chemistry ; Inhibitory Concentration 50 ; Male ; Membrane Proteins ; antagonists & inhibitors ; metabolism ; Microsomes, Liver ; drug effects ; enzymology ; Paeonia ; chemistry ; Rats ; Rats, Wistar

The content of zinc and copper in the hair of 321 persons was detected by an atomic absorption spectropolarimeter. The subjects included young healthy group (35 men, 30 women), middle aged healthy group (72 men, 18 women), arteriosclerosis group (81 men, 20 women), cerebral embolism group (23 men, 8 women) and its control group (23 men, 8 women). The ratio of zinc to copper in the hair of the persons suffered from cerebral embolism was obviously higher than that of healthy controls. By comparing the function of the susceptible factors in cerebral embolism with Feisher's determination analysis method, diastolic pressure was found to be 75.02 percent, the ratio of zinc to copper 16.32 percent. The diagnostic coincidence was found to be above 82 percent.