Aim To investigate the effect of simvastatin on the FKN expression in human umbilical vascular endothelial cells(HUVEC)up-regulated by interleukine-18(IL-18),and the effect on adhesion of FKN to monocyte THP-1.Methods FKN expression in HUVEC was determined by reverse transcription-polymerase chain reaction (RT-PCR), and the adhesion was checked by in vitro Flow chamber.Results Incubation of HUVECs with IL-18 upregulated FKN mRNA expression(P

Objective To observe polyclonal antibodies immobilized on magnetic submicron particles (MSP) as affinity adsorbents and test the reliability of predicted maximum adsorption activity of an enzyme/mutant from a cell lysate (Vs) in recognizing positive mutants.Methods Escherichia coli alkaline phosphatase (ECAP) and Pseudomonas Aeruginosa arylsulfatase (PAAS) were purified by affinity chromatography to serve as immunogens for the preparation of their antisera, which after fractionation by 33％ ammonium sulfate and DEAE-cellulose chromatography yielded the respective polyclonal antibodies.After activation of COOH on MSP, polyclonal antibodies of each enzyme were immobilized to give MSP-polyAb.Activities of an adsorbed enzyme were measured with a chromogenic substrate of 4-nitrphenol by determining absorbance at 405nm after the termination of reaction by alkali.Based on the response curve of activities of the adsorbed enzyme to protein quantities of a lysate, Vs was predicted for comparison.Results The maximum adsorption quantity of ECAP or PAAS on the respective MSP-polyAb was about 2.0mg/g.Specific activity of ECAP after affinity purification was about 70-fold of that of PAAS.ECAP mutant R168K showing about 50％ activity improvement versus ECAP was recognized by comparison of Vs predicted with only 2.5μg of MSP-polyAb;with PAAS mutant G138S as the starting one, the use of 10.0μg of MSP-polyAb to predict Vs recognized the mutants bearing more than 20％ activity improvement.Conclusion With an optimized quantity of MSP-polyAb to predict Vs, weak positive mutants of an enzyme of low activity can be recognized when activities of the adsorbed enzyme/mutant are reliably measured.

An auxiliary training system was explored for the development of creativity of long-termsystem medical undergraduates through scientific researches in spare time.In practice,professionals from research groups of different disciplines were recruited for developing wide-scope theoretical and technical bases of the undergraduates through training among these research groups followed by focused researches on topics of the running projects of these professionals.The undergraduates were engaged in a serial of research activities,including the discovery of problems for reasoning out scientific research projects,the writing of their project proposals,the summary of their data and the writing of reports,to develop their creativity and their qualification for scientific researches.

Objective To explore the effects of trimetazidine (TMZ) on newly onset of type 2 diabetes mellitus(T2DM) in coronary artery disease patients. Methods Using nested-case-control study and a total of 639 coronary artery patients but without T2DM were enrolled. All the patients were followed-up until March, 2015. T2DM was diagnosed with OGTT. The effects of TMZ on T2DM onset, serum levels of fatty acid, HbA1c and insulin were analyzed. Results At the end of the followed-up, a total of 103 T2DM patients were identified. TMZ is still an independent risk factor of newly onset of T2DM after confounding factors were adjusted. TMZ therapy reduced serum HbA1c, FFA and insulin levels. Besides, TMZ treatment was related to proper time to reach the peak of insulin secretion. Conclusion TMZ therapy can reduce newly onset of T2DM in coronary artery disease patients. The affects of lowering serum FFA, which caused insulin resistance, may be its underlying mechanism.

Objective To explore the causes of twisted or tailed DNA bands in agarose gels after electro-phoresis .Methods Prestained and poststained methods were employed to exam 3 kinds of DNA marker bands in agarose gel with GeneGreen and Ethidium Bromide ,respectively .Results Three kinds of DNA marker bands in agarose gel with 1:10000 and 1:5000 concentration of GeneGreen showed obvious distortions and trailing phenomena compared with the same concentration of Ethidium Bromide w hen the prestained method was used for electrophoresis ,which were improved when the poststained method was used in agarose gel with GeneGreen and Ethidium Bromide ,respectively .Conclusion Nucleic acid dye GeneGreen can affect the quali-ty of DNA bands in agarose gel electrophoresis .When the quality of DNA itself ,agarose gel quality ,electro-phoretic fluid quality and voltage are excluded ,the quality of nucleic acid dye should be taken into considera-tion if the bands twisting or tailing occurs when the DNA nucleic acid electrophoresis is carried out by pres-tained method .The quality of DNA electrophoresis bands can be improved by using poststained method or re-placing nucleic acid dye .

Objective To investigate the antagonistic effect of wogonin in combination with 5-fluorouracil (5-FU) on the proliferation of human Hep-G2 hepatocellular carcinoma cells .Methods Human hepatocellular Hep-G2 cells were divided into experimental group (wogonin group ,5-FU group ,wogonin + 5-FU group) and control group .MTT method was used to eval-uate tumor cell proliferation in vitro ,flow cytometry analysis was used to evaluate tumor cell apoptosis .Results The results showed that the wogonin inhibited the proliferation of tumor cells at the concentrations of 5 ,10 ,20 and 40 μmol/L after 24 h and 48 h treatment respectively (P<0.05);5-FU also inhibited the proliferation of tumor cells at the concentrations of 5 ,10 , 20 and 40 mg/L after 24 h and 48 h treatment respectively (P< 0.05) .However when wogonin was combined with 5-FU (wogonin+5-FU group) ,an antagonistic effect was observed on tumor cell proliferation (P<0.05) .When cells were treated by wogonin+5-FU for 48 h ,the combined index (CI) value slowed a dose-dependent antagonistic effect (P<0.05) .Conclusion Wogonin has anti-tumor effect .However when wogonin was combined with 5-FU ,an obvious antagonistic effect on 5-FU′s anti-tumor action was observed .The underlying mechanism deserves further study .

Objective To evaluate cardiovascular benefits in patients with type 2 diabetes mellitus treated with the marketed 11 sodium-glucose co-transporter-2 (SGLT-2) inhibitors and glucagon-like polypeptide-1 (GLP-1) receptor agonism by Bayesian network meta-analysis system. Methods MEDLINE, Embase and Cochrane Library were searched from the establishment of the database to 18 July 2020. The endpoint of the study was adverse cardiovascular events. The effect measures were hazard ratios (HR) and 95% credible intervals (CI). Results Compared with placebo, empagliflozin, canagliflozin, dapagliflozin, albiglutide, dulaglutide, exenatide, liraglutide, semaglutide reduced the risk of major adverse cardiovascular events in patients with type 2 diabetes with HR and 95% CI ranging between 0.75(0.60-0.95)~0.90(0.82-0.99); The risk of heart failure was reduced by empagliflozin, canagliflozin, dapagliflozin and ertugliflozin, with HR and 95%CI ranging between 0.64(0.49-0.82)~0.74(0.65-0.85); Empagliflozin, canagliflozin, dapagliflozin, exenatide, liraglutide and oral semaglutide reduced the incidence of all-cause mortality with HR and 95%CI ranging between 0.52(0.33-0.84)~0.89(0.80-0.99); Empagliflozin, canagliflozin, liraglutide and oral semaglutide can reduce the risk of cardiovascular death events, with HR and 95% CI ranging between 0.54(0.30-0.95)~0.83(0.71-0.96) . Conclusion The order of the cardiovascular benefits of SGLT-2 inhibitors or GLP-1 receptor agonists in patients with type 2 diabetes mellitus complicated with atherosclerotic cardiovascular disease are canagliflozin (the best), empagliflozin, dulaglutide, liraglutide; for patients with type 2 diabetes and heart failure. The order of the cardiovascular benefits for patients with type 2 diabetes and heart failure are empagliflozin, canagliflozin, ertugliflozin, and dapagliflozin.

Objective To investigate the overall incidence and risk of hypertension in the treatment of cancer patients who receive anlotinib and compare the differences between anlotinib and other VEGFR inhibitors. Methods Pubmed, Embase, Cochrane Library, ASCO, CNKI, Wangfang, VIP and CBM databases were searched. Eligible studies were phase II and III prospective clinical trials on cancer patients who received anlotinib and had the hypertension data available. Meta-analysis for the incidence and risk of anlotinib was performed by using R software (version 3.6.0). SPSS software (version 26.0) was used to compare the difference between anlotinib and other VEGFR inhibitors. Results A total of 1387 cancer patients from 13 clinical trials were included in the Meta-analysis. The overall incidences of all grade and high grade hypertension in cancer patients who received anlotinib were about 47.1% (95%CI: 37.7%−56.6%) and 10.6% (95%CI: 7.4%−14.2%). The use of anlotinib was associated with significantly increased risk of all grade (RR=5.58, 95%CI: 2.29−13.60, P<0.01) and high grade hypertension (RR=27.78, 95%CI: 3.56−216.86, P<0.01). In addition, the incidence of high grade hypertension associated with anlotinib was similar to axitinib (RR=0.79, 95%CI: 0.61−1.02, P=0.066) and cabozantinib (RR=0.87, 95%CI: 0.67−1.13, P=0.290). The incidences of rest of other VEGFR inhibitors were lower than that of anlotinib. Conclusions There is a high incidence and significant risk of developing hypertension in cancer patients receiving anlotinib. Adequate monitoring and timely treatment of hypertension is recommended.

Objective To review and analysis the clinical manifestations, occurrence rules, treatment and outcomes of adverse drug reactions caused by anlotinib in order to provide reference for safety and reasonable use of anlotinib in clinical practice. Methods The cases reports of anlotinib were searched in Web of Science, Pubmed, Wiley Online Library, CNKI, Wanfang and VIP. The basic patient information, adverse reaction time, characters, treatment, outcomes and involved systems or organs were collected and analyzed. Results A total of 20 cases were collected, 10 females and 10 males, with a median age of 63.5(36～76 years old). Adverse drug reactions mostly occurred within 2 months after the medication. 52 cases occurred in total, involving 9 systems/organs, of which blood and lymphatic system disorders (all were hypertension) were the most common (21.2%). Conclusion After the administration of anlotinib, the incidence rate of adverse reactions in the cardiovascular system is relatively high. The medication process should be closely monitored, and attention should be paid to monitoring the potential adverse reactions mentioned in the instructions.

OBJECTIVE: To develop a fast, sensitive and cost-effective method based on resonance light scattering (RLS) for characterization of protein solubility to facilitate detection of changes in solubility of mutant proteins. METHODS: We examined the response curve of RLS intensities to the protein concentrations in synchronous scanning mode. The curve intersection points were searched to predict the maximal concentrations of the protein in dispersion state, which defined the solubility of the protein in this given state. Bovine serum albumin (BSA, 0-50 g/L) was used as the model to investigate the influences of pH values (6.5, 7.0, and 7.4) and salt concentrations (0.05, 0.10, 0.15, and 0.20 mol/L) on the determined solubility. The solubility of glutathione S-transferase isoenzymes alpha (GSTA, 0-27.0 g/L) and Mμ (GSTM, 0-20.0 g/L) were estimated for comparison. The RLS-based method was used to determine the solubility of uricase (MGU, 0-0.4 g/L) to provide assistance in improving the solubility of its mutants. RESULTS: We identified two intersection points in the RLS response curves of the tested proteins, among which the lower one represented an approximation of the maximal concentration (or the solubility of the protein) in single molecular dispersion, and the higher one the saturated concentration of the protein in multiple molecular aggregation. In HEPES buffer, the two intersection points of BSA (isoelectric point 4.6) both increased with the increase of pH (6.5-7.4), and their values were ~1.2 g/L and ~33 g/L at pH 7.4, respectively; the latter concentration approached the solubility of commercial BSA in the same buffer at the same pH. The addition of NaCl reduced the values of the two intersection points, and increasing salt ion concentration decreased the values of the lower intersection points. Further characterizations of GSTA and GSTM showed that the low concentration intersection points of the two proteins were ~0.7 g/L and ~0.8 g/L, and their high concentration intersection points were ~10 g/L and ~11 g/L, respectively, both lower than those of BSA, indicating the feasibility of the direct characterization of protein solubility by RLS. The two concentration intersection points of MGU were 0.24 g/L and 0.30 g/L, respectively, and the low concentration intersection point of its selected mutant was increased by 2 times. CONCLUSIONS RLS allows direct characterization of the solubility of macromolecular proteins. This method, which is simple and sensitive and needs only a small amount of proteins, has a unique advantage for rapid comparison of solubility of low-abundance protein mutants.
Hydrogen-Ion Concentration ; Light ; Scattering, Radiation ; Solubility ; Spectrum Analysis