Most cancers are currently incurable, partly due to abnormal post-translational modifications (PTMs). In this study, we initially used multiple myeloma (MM) as a working model and found that SUMOylation activating enzyme subunit 1 (SAE1) promotes the malignancy of MM. Through proteome microarray analysis, SAE1 was identified as a potential target for bioactive colcemid or its derivative colchicine. Elevated levels of SAE1 were associated with poor clinical survival and increased MM proliferation in vitro and in vivo. Additionally, SAE1 directly SUMOylated and upregulated the total protein expression of p27, leading to LLPS-mediated nuclear export of p27. Our study also demonstrated the involvement of SAE1 in other types of cancer cells, and provided the first monomer crystal structure of SAE1 and its key binding model with colchicine. Colchicine also showed promising results in the Patient-Derived Tumor Xenograft (PDX) model. Furthermore, a controlled clinical trial with 56 MM patients demonstrated the clinical efficacy of colchicine. Our findings reveal a novel mechanism by which tumor cells evade p27-induced cellular growth arrest through p27 SUMOylation-mediated nuclear export. SAE1 may serve as a promising therapeutic target, and colchicine may be a potential treatment option for multiple types of cancer in clinical settings.

Objective:To research the application of flurbiprofen compound small dose fentanyl with self-control vein analgesia after laparoscopic cholecystectomy and the influence on blood coagulation function.Methods:102 cases with laparoscopic cholecystectomy who were treated in our hospital from November 2015 to November 2016 were selected and divided into the control group and the research group,with 51 cases in each group.The patients in the control group were treated with postoperative intravenous analgesia with low-dose fentanyl,while the patients in the research group were treated with postoperative intravenous analgesia with flurbiprofen ester compound low-dose fentanyl.Then the fibrinogen (Fg),activated partial prothrombin time (APTT),prothrombin time (PT),platelet count (PLT),substance P,5-hydrocarbon serotonin (5-HT),interleukin 6,8 (IL-6,IL-8) and complications between two groups were observed and compared.Results:Before treatment,there was no statistically significant difference about the Fg,APTT,PT,PLT,substance P,5-HT,IL-6 and IL-8 between two groups (P＞0.05);After treatment,the Fg,APTT,PT,PLT,substance P,5-HT,IL-6 and IL-8 increased in the two groups,while the research group was lower than that of the control group,and the differences were statistically significant (P＜0.05).The postoperative complication rate of research group was lower than that of the control group (P＜0.05).Conclusion:Flurbiprofen ester compound small dose fentanyl with self-control vein analgesia can relieve coagulation function,and inhibit the levels of inflammatory factors.

Genetic studies are traditionally based on single-gene analysis. The use of these analyses can pose tremendous challenges for elucidating complicated genetic interplays involved in complex human diseases. Modern pathway-based analysis provides a technique, which allows a comprehen-sive understanding of the molecular mechanisms underlying complex diseases. Extensive studies uti-lizing the methods and applications for pathway-based analysis have significantly advanced our capacity to explore large-scale omics data, which has rapidly accumulated in biomedical fields. This article is a comprehensive review of the pathway-based analysis methods––the powerful methods with the potential to uncover the biological depths of the complex diseases. The general concepts and procedures for the pathway-based analysis methods are introduced and then, a comprehensive review of the major approaches for this analysis is presented. In addition, a list of available path-way-based analysis software and databases is provided. Finally, future directions and challenges for the methodological development and applications of pathway-based analysis techniques are dis-cussed. This review will provide a useful guide to dissect complex diseases.

Objective To analyze the impact of parental Metabolic Syndrome(MS)on adolescents,and to explore the familial aggregation of MS with its components.Methods Using a 1:3 case-control familial study design to choose 26 MS male patients as proband and 78 healthy men as controls.Data regarding phenotype of their adolescence offspring were collected.Height,weight,waist circumference(WC),blood pressure,body mass index(BMI),waist-to-hip ratio(WHR)and waist-to-height ratio(WHtR)were measured or calculated.FPG,TC,TG,HDL-C and LDL-C were detected by automatic biochemical analyzer and hs-CRP was detected.Results WC,WHtR,WHR,DBP and hs-CRP of those adolescents with paternal MS were significantly higher than in controls(P＜0.05).Rates of MS,Obesity depend WC,low level of HDL-C of adolescent with paternal MS were significantly higher than in controls(P＜0.05).The rate of number on MS was significantly higher in case group than in control(r=0.231,P＜0.05).Conclusion The phenotypes of MS were different between adolescents with or without parental MS,indicating that the familial aggregation of MS had been existed in their adolescent offspring,and mainly presented in central obesity,increased blood pressure and inflammation.

OBJECTIVETo establish HPLC fingerprint of HQSM capsules,and a new method for correlativity analysis between fingerprint peaks of HQSM and its relevant herbs based on the fingerprint analysis.

METHODThe chromatographic fingerprints of HQSM and its relevant herbs were analyzed by HPLC configured with DAD. The similarity of the HPLC fingerprints between HQSM and its relevant herbs and the comparison of UV spectra of the main peaks in both of fingerprints were used as indices to evaluate the correlativity.

RESULTThe HPLC fingerprint with 16 common peaks was established and the chromatographic peaks were determined.

CONCLUSIONThe established method effectively controlled the quality of HQSM and establised the correlativity between HQSM and its relevant herbs, which would contribute to deduce the chemical components or sources of traditional Chinese medicine prescription.

Capsules ; chemistry ; Chromatography, High Pressure Liquid ; Drugs, Chinese Herbal ; chemistry ; Plants, Medicinal ; chemistry

Aged ; Anthracosis ; physiopathology ; Humans ; Lung ; physiopathology ; Male ; Middle Aged ; Pulmonary Ventilation ; Respiratory Function Tests