[This corrects the article DOI: 10.1016/j.apsb.2019.01.013.].

AIM:This study aims to investigate the impact of TWIK-1 channels on abnormal pacemaker activi-ties induced by hypokalemia and to elucidate the underlying mechanisms.METHODS:The gene sequences encoding hu-man TWIK-1,specific TWIK-1 shRNA and TWIK-1-T118i mutant were synthesized and subsequently subcloned into lenti-viral vectors.To knock down the TWIK-1 gene in human induced pluripotent stem cell-derived cardiomyocytes(hiPSC-CMs),the cells were transduced with lentivirus carrying the specific TWIK-1 shRNA sequences.For the overexpression of TWIK-1 or the TWIK-1-T118i mutant in HL-1 mouse cardiomyocytes,the cells received lentiviral transduction containing the respective gene sequences.Patch-clamp techniques were employed to assess the effects of 1 mmol/L extracellular K+on the membrane potentials and whole-cell currents of the cardiomyocytes.RESULTS:Under conditions of 1 mmol/L extra-cellular K+,depolarization of membrane potentials was observed in the hiPSC-CMs and the HL-1 mouse cardiomyocytes ex-pressing human TWIK-1 channel,leading to the induction of abnormal pacemaker activities.This phenomenon could be reversibly abolished by the removal of extracellular Na+or inhibited through TWIK-1 knockdown.In contrast,the mem-brane potentials of HL-1 mouse cardiomyocytes expressing human TWIK-1-T118i mutant hyperpolarized,with no occur-rence of abnormal pacemaker activities.The hiPSC-CMs exhibiting abnormal pacemaker activities at 1 mmol/L extracellu-lar K+demonstrated TWIK-1-like Na+leak currents,which were blocked by quinine,a non-selective blocker of TWIK-1.CONCLUSION:The TWIK-1 channels play a critical role in the development of hypokalemia-induced abnormal pace-maker activities in human cardiomyocytes by facilitating Na+leak currents.

AIM:This study aims to investigate the impact of TWIK-1 channels on abnormal pacemaker activi-ties induced by hypokalemia and to elucidate the underlying mechanisms.METHODS:The gene sequences encoding hu-man TWIK-1,specific TWIK-1 shRNA and TWIK-1-T118i mutant were synthesized and subsequently subcloned into lenti-viral vectors.To knock down the TWIK-1 gene in human induced pluripotent stem cell-derived cardiomyocytes(hiPSC-CMs),the cells were transduced with lentivirus carrying the specific TWIK-1 shRNA sequences.For the overexpression of TWIK-1 or the TWIK-1-T118i mutant in HL-1 mouse cardiomyocytes,the cells received lentiviral transduction containing the respective gene sequences.Patch-clamp techniques were employed to assess the effects of 1 mmol/L extracellular K+on the membrane potentials and whole-cell currents of the cardiomyocytes.RESULTS:Under conditions of 1 mmol/L extra-cellular K+,depolarization of membrane potentials was observed in the hiPSC-CMs and the HL-1 mouse cardiomyocytes ex-pressing human TWIK-1 channel,leading to the induction of abnormal pacemaker activities.This phenomenon could be reversibly abolished by the removal of extracellular Na+or inhibited through TWIK-1 knockdown.In contrast,the mem-brane potentials of HL-1 mouse cardiomyocytes expressing human TWIK-1-T118i mutant hyperpolarized,with no occur-rence of abnormal pacemaker activities.The hiPSC-CMs exhibiting abnormal pacemaker activities at 1 mmol/L extracellu-lar K+demonstrated TWIK-1-like Na+leak currents,which were blocked by quinine,a non-selective blocker of TWIK-1.CONCLUSION:The TWIK-1 channels play a critical role in the development of hypokalemia-induced abnormal pace-maker activities in human cardiomyocytes by facilitating Na+leak currents.

[This corrects the article DOI: 10.1016/j.apsb.2019.01.013.].

Bicyclol is a synthetic drug for hepatoprotection in clinic since 2004. Preliminary clinical observations suggest that bicyclol might be active against hepatitis C virus (HCV) with unknown mechanism. Here, we showed that bicyclol significantly inhibited HCV replication and in hepatitis C patients. Using bicyclol as a probe, we identified glycolipid transfer protein (GLTP) to be a novel restrictive factor for HCV replication. The GLTP preferentially bound host vesicle-associated membrane protein-associated protein-A (VAP-A) in competition with the HCV NS5A, causing an interruption of the complex formation between VAP-A and HCV NS5A. As the formation of VAP-A/NS5A complex is essential for viral RNA replication, up-regulation of GLTP by bicyclol reduced the level of VAP-A/NS5A complex and thus inhibited HCV replication. Bicyclol also exhibited an inhibition on HCV variants resistant to direct-acting antiviral agents (DAAs) with an efficacy identical to that on wild type HCV. In combination with bicyclol, DAAs inhibited HCV replication in a synergistic fashion. GLTP appears to be a newly discovered host restrictive factor for HCV replication, Up-regulation of GLTP causes spontaneous restriction of HCV replication.

Objective: To investigate the positioning based on the relative retention time of fingerprinting and to establish a new quality evaluation method for traditional Chinese medicine preparations, using one chemical reference substance to calcutate multi- components simultaneously. Methods: Employed icariin as the maker component, icariin relative correction factors (RCF) of epimedin C to icariin, asperosaponin VI to icariin, psoralen to icariin and angelicin to icariin were ealeatated in the chromatographic conditions for determination of the four components in Xianling Gubao Capsule (XGC). The contents of icariin were determined by external standard method, and those of epimedin C, asperosaponin VI, psoralen and angelicin were calculated by icariin and their RCF. The accuracy of the new method was evaluated by comparing the relative retention times and calculating the content which using different brands columns for determination. Results: The analysis methods were established,the linearity was good when sample volume was in the range of at 8.2—328.0 ng for icariine(r = 0.999 5), 0.055 6—2.224 μg for epimedin C (r = 0.999 6), 0.144 1—5.764 μg for asperosaponin VI (r = 0.999 6), 5.4—215.2 ng (r = 0.998 0) for psoralen, 6.6—265.6 ng (r = 0.998 5) for angelicin. The average recoveries of asperosaponin VI, psoralen and psoralen were 97.59%, 98.58%, 98.11%, 97.86%, 98.22%, respectively. The RSDs of recovery were all less than 2.0%; There has been no significant difference between the calculated contents and the determined contents, according to the angle cosine value. Conclusion: The method can control the components without providing epimedin C, asperosaponin VI, psoralen, and angelicin reference. The method is not only save reference substance and medicine resources, but also suitable quality evaluation pattern for TCM preparation. This new method made fingerprinting more meaningful in TCM quality control.

We have achieved good effects in realizing the dynamic management of probity -risk, positively preventing the unhealthy tendencies in the medicine purchases and sales and medical services from the sources , and promoting implementation of combating corruption and upholding integrity by exploring the prevention and control mechanism including prevention , monitoring and disposition and strengthening the education , institution, supervi-sion, accountability and so on .

Background Angle Kappa is the angle between the pupillary axis and visual axis,and it is a major consideration in corneal refractive surgery and strabismic surgery.Researches showed that age and refractive status affect angle Kappa value,and additionally,the measuring results of angle Kappa are associated with instruments.Objective This study was to investigate and weight the influences of axial length,anterior chamber depth and corneal curvature to angle Kappa.Methods A cross-sectional study was designed.Fifty health volunteers were included from Dec 2009 to Aug 2010,with the age of 18-38 years and average diopter of-1.0 D and best corrected visual acuity of 1.0.The horizontal and vertical angle Kappa was binocular measured with a testing machine designed by laboratory of School of Optometry & Ophthalmology Wenzhou Medical University.IOLMaster was employed to measure the ocular axial length,anterior chamber depth and corneal curvature radius.A multiple linear regression model was established to analyze the influences of axial length,anterior chamber depth and corneal curvature radius to angle Kappa.Results An efficacious regression equation was established as Y =15.554-0.587X1+0.724X2+ 0.232X3 with the independent variables as axial length(X1),anterior chamber depth (X2),corneal curvature (X3) and dependent variable as horizontal angle Kappa (Y) (R =0.788,R2 =0.621,P =0.000).Horizontal angle Kappa showed a negative correlation with axial length (b1 =-0.587,β1 =-1.002,P =0.000) and a positive correlation with anterior chamber depth (b2 =0.724,β32 =0.296,P =0.030).No significant correlation was found between corneal curvature radius and horizontal angle Kappa (b3 =-0.232,β3 =-0.068,P=0.338).A new regression equation was Y =14.235-0.622X1 + 0.824X2 after removed the corneal curvature variable (R =0.786,R2=0.618,P =0.000),with a negative correlation between horizontal angle Kappa and axial length (b1 =-0.622,β1 =-1.062,P＜0.05) or positive correlation between horizontal angle Kappa and the anterior chamber depth (b2 =0.824,β2 =0.337,P＜0.05).In addition,a multiple linear regression equation among 3 independent variables and dependent variable of vertical angle Kappa was Y =0.492-0.020X1 +0.038X2 +0.089X3 (R =0.436,R2 =0.191,P =0.000).However,no significant correlations were seen between vertical angle Kappa and axial length,anterior chamber depth or corneal curvature radius (all at P ＞ 0.05).Conclusions Ocular axial length and anterior chamber depth have an obvious influence to horizontal but not vertical angle Kappa.Axial length appears to have more influence to horizontal angle Kappa than anterior chamber depth.