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Enzymes are widely used in chemical and pharmaceutical industries because of their advantages of high efficiency and specificity. However， the shortcomings of the free enzymes， such as poor stability and difficulty in recycling， limit their application. Therefore， the immobilization and application of enzymes have become one of the research hotspots. The selection of the immobilization carriers is a critical step in the process of enzyme immobilization. Metal-organic frameworks（MOFs）， a kind of porous materials， are formed by the coordination of metal ions or metal clusters with organic ligands. As an emerging immobilization carrier， its advantages such as high porosity， strong stability， and surface modifiability make it ideal for immobilized enzyme carriers. By immobilizing the free enzyme on MOFs， the above mentioned deficiencies of the free enzymes can be effectively solved， which greatly broaden the applicable condition. Ligand fishing is a method to find receptor-specific ligands from complex components， which has the advantages of high efficiency， simple sample pretreatment and high specificity. The MOF-enzyme complex formed by enzyme immobilization can act as a "fishing rod" for ligand fishing， which can screen out the targets from the complex system of components. The complex chemical composition and various active ingredients of traditional Chinese medicine（TCM） make the ligand fishing technology to play a big role in the screening of enzyme inhibitors from TCM. And the screened enzyme inhibitors are expected to be further developed into the lead compounds with good efficacy and low adverse effects， so the immobilized enzymes of MOFs have a wide application in the screening of active ingredients from TCM. Based on this， this paper summarized the methods of immobilized enzymes of MOFs in recent years， analyzed the characteristics， advantages and disadvantages of each method， and summarized the laws of preparation conditions and mechanisms. Meanwhile， the application and future development of immobilized enzymes of MOFs in the field of enzyme inhibitor screening from TCM were also summarized and prospected， with a view to providing a reference for the development of natural ingredients and the modernization of TCM.
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OBJECTIVE：To establish the metho d for the content determination of 8 nucleosides in wild and cultivated Pinellia ternate，and to conduct the difference analysis. METHODS ：The contents of uracil ，uridine，inosine，xanthine，adenine， guanosine，β-thymidine and adenosine in 20 batches of P. ternate （wild product YS 1-YS8，cultivated product ZP 1-ZP12）were determined by HPLC method. Based on the contents of the above 8 nucleosides，cluster analysis ，principal component analysis （PCA），partial least squares analysis （OPLS-DA）were used to comprehensively evaluate the wild and cultivated P. ternata . RESULTS：The contents of uracil ，uridine，inosine，xanthine，adenine，guanosine，β-thymidine and adenosine in 20 batches of P. ternate were 0.02-0.24，0.01-0.24，0.06-0.37，0.02-0.14，0.04-0.22，0.14-0.42，0.01-0.09，0-0.32 mg/g，respectively. Cluster analysis，PCA and OPLS-DA showed that 8 batches of wild P. ternate （YS1-YS8）were clustered into one category ，and 12 batches of cultivated P. ternate （ZP1-ZP12）were clustered into one category. Main characteristic markers of wild P. ternate were guanosine，uridine，adenosine and adenine ，while the main characteristic markers of cultivated P. ternate were urinine ，xanthine， inosine，and β-thymidine. CONCLUSIONS：The method for the content determination of 8 nucleosides in P. ternate is established. Nucleosides as quality markers can effectively distinguish wild and cultivated P. ternata ，and the quality of the wild P. ternate was better than that of cultivated P. ternate .
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Objective To investigate the expression of carcinoembryonic antigen-related cell adhesion molecule 19 (CEACAM19) in colorectal cancer tissues,and evaluate the clinical pathological characters and prognostic significance.Methods Ninety-eight patients with colorectal cancer in Beijing Huairou Hospital from July 2015 to July 2018 were selected.The expression level of CEACAM 19 protein in primary colorectal cancer and corresponding non-tumor tissues (＞2 cm) was detected by immunohistochemistry.The correlation between clinical pathological characters and CEACAM19 expression level was analyzed.The prognostic influencing factors were analyze by univariate and multivariate Cox regression methods.Survival curve was drawn by Kaplan-Meier method.Results The high expression rate of CEACAM19 in colorectal cancer tissues was significantly higher than that in adjacent non-tumor tissues:69.4％ (68/98) vs.16.3％ (16/98),and there was statistical difference (x2 =45.060;P ＜ 0.01).Expression of CEACAM19 in colorectal cancer tissues was significantly associated with TNM stage (P＜ 0.05),and was not associated with age,gender,tumor diameter,histological differentiation,tumor location,lymph node stage and invasion depth (P ＞ 0.05).Univariate Cox regression analysis result showed that lymph node stage,TNM stage and CEACAM19 expression were influencing factors of overall survival in patients with colorectal cancer (P ＜ 0.05 or ＜ 0.01),and the TNM stage and CEACAM19 expression were influencing factors of disease-free survival in patients with colorectal cancer (P ＜ 0.01).Multivariate Cox regression analysis result showed that TNM stage increased and CEACAM19 high expression were independent risk factors of overall survival (HR =2.628 and 0.199,95％ CI 1.147 to 6.021 and 0.045 to 0.868,P =0.022 and 0.032) and disease-free survival (HR =2.009 and 0.303,95％ CI 0.965 to 4.185 and 0.101 to 0.911,P =0.048 and 0.034) in patients with colorectal cancer.Survival curve analysis result showed that the median overall survival and disease-free survival in CEACAM19 low expression patients were significantly longer than CEACAM19 high expression patients (47.9 months vs.27.8 months and 43.2 months vs.26.3 months,P ＜ 0.01);the median overall survival and disease-free survival in TNM Ⅰ to Ⅱ stage were significantly longer than TNM Ⅲ stage patients (43.9 months vs.24.2 months and 39.3 months vs.23.7 months,P ＜ 0.01).Conclusions The CEACAM19 in colorectal cancer tissues is high expression,and the CEACAM19 expression level can be used as biomarker for prediction the prognosis of colorectal cancer.
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Objective@#To investigate the expression of carcinoembryonic antigen-related cell adhesion molecule 19 (CEACAM19) in colorectal cancer tissues, and evaluate the clinical pathological characters and prognostic significance.@*Methods@#Ninety-eight patients with colorectal cancer in Beijing Huairou Hospital from July 2015 to July 2018 were selected. The expression level of CEACAM19 protein in primary colorectal cancer and corresponding non-tumor tissues (>2 cm) was detected by immunohistochemistry. The correlation between clinical pathological characters and CEACAM19 expression level was analyzed. The prognostic influencing factors were analyze by univariate and multivariate Cox regression methods. Survival curve was drawn by Kaplan-Meier method.@*Results@#The high expression rate of CEACAM19 in colorectal cancer tissues was significantly higher than that in adjacent non-tumor tissues: 69.4% (68/98) vs. 16.3% (16/98), and there was statistical difference (χ2 = 45.060; P<0.01). Expression of CEACAM19 in colorectal cancer tissues was significantly associated with TNM stage (P<0.05), and was not associated with age, gender, tumor diameter, histological differentiation, tumor location, lymph node stage and invasion depth (P>0.05). Univariate Cox regression analysis result showed that lymph node stage, TNM stage and CEACAM19 expression were influencing factors of overall survival in patients with colorectal cancer (P<0.05 or <0.01), and the TNM stage and CEACAM19 expression were influencing factors of disease-free survival in patients with colorectal cancer (P<0.01). Multivariate Cox regression analysis result showed that TNM stage increased and CEACAM19 high expression were independent risk factors of overall survival (HR = 2.628 and 0.199, 95% CI 1.147 to 6.021 and 0.045 to 0.868, P = 0.022 and 0.032) and disease-free survival (HR = 2.009 and 0.303, 95% CI 0.965 to 4.185 and 0.101 to 0.911, P = 0.048 and 0.034) in patients with colorectal cancer. Survival curve analysis result showed that the median overall survival and disease-free survival in CEACAM19 low expression patients were significantly longer than CEACAM19 high expression patients (47.9 months vs. 27.8 months and 43.2 months vs. 26.3 months, P<0.01); the median overall survival and disease-free survival in TNM Ⅰ to Ⅱ stage were significantly longer than TNM Ⅲ stage patients (43.9 months vs. 24.2 months and 39.3 months vs. 23.7 months, P<0.01).@*Conclusions@#The CEACAM19 in colorectal cancer tissues is high expression, and the CEACAM19 expression level can be used as biomarker for prediction the prognosis of colorectal cancer.
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Objective To observe the clinical effects of pemetrexed alone or pemetrexed combined with platinum in the treatment of advanced non -squamous non -small cell lung cancer who failed first line therapy. Methods 34 patients with advanced NSCLC who had failed to previous chemotherapy and all of these patients had been confirmed with pathology or cytology.Pemetrexed monotherapy group included 14 cases and pemetrexed plus platinum group included 20 cases.21 days as one cycle.All patients who received 2 or more cycles could be evaluated. Results No complete response (CR)occurred.There were 3 cases of partial response (PR),15 cases of stable disease(SD)and 16 cases of progressive disease(PD)in the 34 patients.The disease control rate was 52.9%(18 /34).The median progressive free survival was 2.7 months.The major toxic reaction included leucopenia,anemia and gastrointestinal response.Conclusion Pemetrexed or pemetrexed combined with platinum can prolong the survival time of some patients of non -squamous non -small cell lung cancer who failed first line therapy.The toxic effects can be tolerated.
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Objective To observe the efficacy and untoward reactions of FOLFOX4 regimen and XELOX regimen in the treatment of patients with advanced colorectal cancer.Methods Fifty four advanced colorectal cancer patients were randomly divided into two groups.Group A (FOLFOX4):28 patients were treated with oxaliplatin 85 mg/m2 on day 1,LV 200 mg/m2 as a 2h infusion followed by bolus 5 -FU 400 mg/m2 and a 24h infusion of 5 -Fu 600 mg/m2 ,repeated for consecutive days every 2 weeks.One cycle was 14 days and efficacy was evaluated after 4 cycles.Group B(XELOX):26 patients were treated with oxaliplation 130mg/m2 on day 1,capecitabine 1 000 mg/m2 orally daily for 14 days.One cycle was 21 or 28 days and efficacy was evaluated after 2 cycles.Efficacy of the two groups was evaluated at 2 cycles.Results All 54 patients were available for evaluating objective response.In A group,the overall response rate was 46.4%,and the overall response rate was 42.3% in B group.The overall response rate of A group was slightly higher than B group,but there was no statistically significant difference(χ2 =0.093,P =0.791 ).Adverse reactions:thrombocytopenia incidence rate and the peripheral nerve toxicity had no significant differences between the two groups(χ2 =0.552,0.108,P =0.550,0.787).The incidence rates of nausea, vomit,diarrhea and leucocytopenia in B group were lower than those in A group(χ2 =9.495,4.862,6.273,P =0.003,0.033,0.108).The incidence rate of hand -foot syndrome was higher in B group than in A group(χ2 =13.389,P =0.000),but the severity was less(grade Ⅰ ~Ⅱ).Conclusion The response rate in the treatment of advanced colorectal cancer was similar between XELOX and FOLFOX4 regiments,but XELOX regiment has the advantages of more convenience,better safety.Thus,XELOX regiment is worth recommending as a first -line therapy for the treatment of patients with advanced colorectal cancer.
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Objective To investigate the association between polymorphism of cytochrome P450 subfamily Ⅺ A polypeptide 1 (CYP11A1) gene and polycystic ovarian syndrome (PCOS) in Chinese population. Methods From May 2005 to Dec.2008,290 PCOS cases treated in the First affiliated hospital of Anhui Medical University matched with 344 reproductive women as controls were enrolled in this study. Genotypes of 7 tagging single nucleotide polymorphisms(tSNP,rs12438594,rs4077582,rs9806234,rsl6968477,rs4887139,rs1843090,rsl 1632698)covering CYP11A1 gene (r~2≥0.8) and 3 microsatellite markers (D15S1547,D16S520,D15S1546) were chosed from the phase II database of Han population in HapMap data.Genotype and frequency of allele were detected by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and haplotype of gene polymorphism were analyzed in 290 PCOS cases and 344 controls.Results Among 7 tSNPs and 3 microsatellite markers,the frequency of rs4077582,D15S1547,D15S1546 and rsl 1632698 between two groups reached statistical difference (P =0.010,0.044,0.018 and 0.026).The allele frequency of rs4O77582,rs4887139,rsl843090,D15S1547 and Dl 6S520 showed significant difference between two groups(P=0.002,0.048,0.030,0.001 and 0.024).Among 5 haplotype of CYP11A1(ACGCA13/6/9AG,ACGTA16/6/11AA,GCACG12/8/8AA,GTACA14/4/7GG,GTGCA13/6/7AG),the frequency of GTACA14/4/7GG and ACGCA13/6/9AG were 7.8% (45/580) and 25.3% (147/580) in PCOS group and 11.9% and 19.6% in control group,which showed statistical difference (P< 0.05 ).There was no significant difference in the level of serum androgen at difference genotype from rs4077582 between two groups (P>0.05).Conclusion The polymorphism of CYP11A1 gene was associated with PCOS,however,the relationship between gene sequence covered by tSNP/microsatellite markers and hyperandrogenism of PCOS should be further investigated.