AIM:To investigate the impact of Kir2.1 channels on abnormal spontaneous pacemaker activities induced by hypokalemia and to elucidate the underlying mechanisms.METHODS:Human induced pluripotent stem cell-derived cardiomyocytes(hiPSC-CMs)were transfected with lentiviral particles containing sequences for human Kir2.1,the Kir2.1-E224G mutant,or Kir4.1.Patch clamp techniques were employed to examine the effects of low extracellular potassium concentration([K+]e)of 1 mmol/L on the resting membrane potentials and whole-cell currents of the cells in each group,assessed via both current and voltage clamp modes.RESULTS:Under conditions of 1 mmol/L[K+]e,cur-rent clamp data revealed that hiPSC-CMs overexpressing Kir2.1 channels exhibited both hyperpolarized and depolarized resting membrane potentials,with the depolarized state triggering abnormal pacemaker activities.In contrast,cells overex-pressing the Kir2.1-E224G mutant or Kir4.1 channels displayed only hyperpolarized resting membrane potentials.Voltage clamp analysis indicated that hiPSC-CMs overexpressing Kir2.1 channels produced"N"-shaped whole-cell currents,whereas cells expressing the Kir2.1-E224G mutant or Kir4.1 exhibited typical K+currents.CONCLUSION:Kir2.1 channels play a crucial role in mediating hypokalemia-induced abnormal spontaneous pacemaker activities in human car-diomyocytes through their inward rectification properties.

AIM:To investigate the impact of Kir2.1 channels on abnormal spontaneous pacemaker activities induced by hypokalemia and to elucidate the underlying mechanisms.METHODS:Human induced pluripotent stem cell-derived cardiomyocytes(hiPSC-CMs)were transfected with lentiviral particles containing sequences for human Kir2.1,the Kir2.1-E224G mutant,or Kir4.1.Patch clamp techniques were employed to examine the effects of low extracellular potassium concentration([K+]e)of 1 mmol/L on the resting membrane potentials and whole-cell currents of the cells in each group,assessed via both current and voltage clamp modes.RESULTS:Under conditions of 1 mmol/L[K+]e,cur-rent clamp data revealed that hiPSC-CMs overexpressing Kir2.1 channels exhibited both hyperpolarized and depolarized resting membrane potentials,with the depolarized state triggering abnormal pacemaker activities.In contrast,cells overex-pressing the Kir2.1-E224G mutant or Kir4.1 channels displayed only hyperpolarized resting membrane potentials.Voltage clamp analysis indicated that hiPSC-CMs overexpressing Kir2.1 channels produced"N"-shaped whole-cell currents,whereas cells expressing the Kir2.1-E224G mutant or Kir4.1 exhibited typical K+currents.CONCLUSION:Kir2.1 channels play a crucial role in mediating hypokalemia-induced abnormal spontaneous pacemaker activities in human car-diomyocytes through their inward rectification properties.

Objective To explore the differential expression of the key microfilament cytoskeleton-binding proteins in immature dendritic cells(imDCs)during antigen phagocytosis.Methods Monocytes(MOs)were isolated from peripheral blood of healthy individuals and cultured with recombinant human granulocyte-macrophage colony stimulating factor(rhGM-CSF)and recombinant human interleukin-4(rhIL-4)for 6 days to obtain imDCs.ImDCs were co-cultured with low molecular weight(40 kDa)and high molecular weight(150 kDa)dextrans for 1,3 and 6 hours,respectively.Flow cytometry was used to detect the percentage of imDCs phagocytosing dextran and the expression of immunophenotype molecules.The localization of filamentous actin(F-actin),PFN1,WASP,and α-actinin in cells were observed by immunofluorescence imaging.The differential expression of MCBPs at the mRNA and protein levels were respectively detected by q-PCR and Western blotting.Finally,the MCBPs with the highest component coefficients were identified based on the stepwise regression and principal component analysis method in systems biology algorithms.Results During the process of antigen phagocytosis,imDCs phagocytized low molecular weight antigens at a faster rate,with a phagocytic duration of approximately three hours.Their cell phenotypes and morphology gradually differentiated into mDCs,and F-actin remodeling was occurred significantly.The expression of MCBPs such as PFN1,CDM,WASP,CAPZB,Filamin A,α-actinin were downregulated,while the expression of WAVE1,Arp2/3 complex,and Fascin were upregulated.The mRNA expression of signaling protein Rac1 was upregulated,while the mRNA expressions of CDC42 and RhoA were downregulated.The immunofluorescence results showed that PFN1,WASP,and α-actinin were transposed during the antigen phagocytosis process of imDCs.The results of stepwise regression and principal component analysis showed that PFN1 had the highest component coefficient.Conclusions PFN1 may be a key MCBPs involved in the process of antigen phagocytosis of imDCs,which is of great significance for further understanding the relationship between changes in the cytoskeleton structure of imDCs and their immunological functions.

Objective To study the probability distribution of Mosquito ovitrap Index(MOI)risk of dengue Aedes vector,so as to provide a new method for more scientific and accurate MOI risk assessment.Methods Cubic spline function,cumulative probability distribution and python language programming were used to fit and analyze the MOI surveillance data of Guangzhou from 2016 to 2019 years.Results The probability distribution table and distribution figure of MOI risk assessment in Guangzhou from January to December were developed.From January to December,the MOI critical values were 7.54～60.12 and 5.05～34.10 with a cumulative probability less than 0.01 or 0.05 respectively.The critical value was the lowest in January,followed by December and February.The highest was in June,followed by May and July.From January to December,the probabilities of MOI risk grade of transmission,outbreak and epidemic were 5.07%～66.60%,0.25%～36.19%and 0.00%～16.80%respectively.The lowest risk probability of transmission,outbreak and epidemic occurred in January,followed by February respectively.The highest risk probability values appeared in July,July and June,followed by June,June and May respectively.Conclusion The probability distribution of MOI risk in each month in Guangzhou had significant seasonal growth and decline laws and characteristics,which were worthy of attention in the monitoring,evaluation and control of dengue Aedes vector.It provided a new analysis method for MOI risk assessment fitting based on cubic spline functions and cumulative probability distribution.

Objective To investigate the value of the quantitative analysis of digital subtraction angiography(DSA)and dynamic contrast-enhanced CT in evaluating the efficacy of hepatic artery infusion chemotherapy(HAIC)for liver cancer.Methods Fifty patients who were clinically diagnosed with primary liver cancer and treated with HAIC at least 3 times were enrolled in the study.Based on the enhanced CT scans taken within 1 week before the 1st and 3rd HAIC,patients were divided into good response group(CR+PR)and poor response group(SD+PD)according to the modified response evaluation criteria in solid tumor.The hemodynamic parameters[time to peak(TP),peak density(PV),and slope of the rising edge of the time-density curve(SU)]of liver cancer on DSA before treatment and after two HAIC,as well as the changes in the CT values of liver cancer in each phase of CT enhancement were compared,and then sensitivity analysis was conducted.Significant indicators were further analyzed with Logistic regression and ROC curve to assess their efficacies in evaluating HAIC response in liver cancer.Results The differences in pre-treatment CT values and DSA indicators between two groups were trivial(P>0.05).All patients successfully completed HAIC twice.The enhanced CT taken 1 week before the 3rd HAIC showed reductions in the arterial-and venous-phase CT values in good response group(P<0.05),while no significant difference was found in the delayed-phase CT value(P>0.05).At the 3rd HAIC,DSA angiography demonstrated significant reductions in PV and SU,and a significant prolongation of TP in good response group(P<0.05);while there were no significant differences in various indicators in poor response group.Regression analysis showed that arterial-phase CT values and DSA angiography SU were significantly correlated with therapeutic efficacy.ROC curve results indicated that arterial-phase CT values and SU were effective indicators for evaluating therapeutic efficacy.Conclusion The SU from DSA angiography and the CT values from dynamic contrast-enhanced CT which can objectively reflect the changes in blood supply of liver cancer after HAIC and are associated with HAIC efficacy can serve as radiological evidence for evaluating HAIC response.

OBJECTIVE To establish the drug use evaluation(DUE) standard of ticagrelor, and to provide a reference for the rational clinical application of ticagrelor. METHODS Based on the ticagrelor drug label, related guidelines and literature, combined with clinical expert consultation results, DUE standard from three levels (indications, medications and medication results) was established. A retrospective survey was conducted to evaluate the inpatients using ticagrelor from January 2021 to December 2021 in the Second Affiliated Hospital of Fujian University of Traditional Chinese Medicine. RESULTS The DUE of ticagrelor was divided into three levels, including 3 first-level indexes, 14 second-level indexes and 60 third-level indexes. A total of 263 cases of using ticagrelor were included, of which the irrational rate was 72.62%. The irrational cases were mainly off-label use (60.08%), inappropriate drug conversion(14.83%) and unreasonable usage and dosage(5.70%), etc. CONCLUSION The established DUE standard of ticagrelor is scientific, practical and feasible, which can provide reference for clinical rational drug use and prescription evaluation.

Background/Aims: There may be many predictors of anticoagulation-related gastrointestinal bleeding (GIB), but until now, systematic reviews and assessments of the certainty of the evidence have not been published. We conducted a systematic review to identify all risk factors for anticoagulant-associated GIB to inform risk prediction in the management of anticoagulation- related GIB. Methods: A systematic review and meta-analysis were conducted to search PubMed, EMBASE, Web of Science, and Cochrane Library databases (from inception through January 21, 2022) using the following search terms: anticoagulants, heparin, warfarin, dabigatran, rivaroxaban, apixaban, DOACs, gastrointestinal hemorrhage, risk factors. According to inclusion and exclusion criteria, studies of risk factors for anticoagulation-related GIB were identified. Risk factors for anticoagulant-associated GIB were used as the outcome index of this review. Results: We included 34 studies in our analysis. For anticoagulant-associated GIB, moderate-certainty evidence showed a probable association with older age, kidney disease, concomitant use of aspirin, concomitant use of the antiplatelet agent, heart failure, myocardial infarction, hematochezia, renal failure, coronary artery disease, helicobacter pylori infection, social risk factors, alcohol use, smoking, anemia, history of sleep apnea, chronic obstructive pulmonary disease, international normalized ratio (INR), obesity et al. Some of these factors are not included in current GIB risk prediction models. such as anemia, co-administration of gemfibrozil, co-administration of verapamil or diltiazem, INR, heart failure, myocardial infarction, etc. Conclusions The study found that anemia, co-administration of gemfibrozil, co-administration of verapamil or diltiazem, INR, heart failure, myocardial infarction et al. were associated with anticoagulation-related GIB, and these factors were not in the existing prediction models. This study informs risk prediction for anticoagulant-associated GIB, it also informs guidelines for GIB prevention and future research.

Objective To monitor the susceptibility of clinical isolates to antimicrobial agents in healthcare facilities in major regions of China in 2023.Methods Clinical isolates collected from 73 hospitals across China were tested for antimicrobial susceptibility using a unified protocol based on disc diffusion method or automated testing systems.Results were interpreted using the 2023 Clinical & Laboratory Standards Institute (CLSI) breakpoints.Results A total of 445199 clinical isolates were collected in 2023,of which 29.0％ were gram-positive and 71.0％ were gram-negative.The prevalence of methicillin-resistant strains in Staphylococcus aureus,Staphylococcus epidermidis and other coagulase-negative Staphylococcus species (excluding Staphylococcus pseudintermedius and Staphylococcus schleiferi) (MRSA,MRSE and MRCNS) was 29.6％,81.9％ and 78.5％,respectively.Methicillin-resistant strains showed significantly higher resistance rates to most antimicrobial agents than methicillin-susceptible strains (MSSA,MSSE and MSCNS).Overall,92.9％ of MRSA strains were susceptible to trimethoprim-sulfamethoxazole and 91.4％ of MRSE strains were susceptible to rifampicin.No vancomycin-resistant strains were found.Enterococcus faecalis had significantly lower resistance rates to most antimicrobial agents tested than Enterococcus faecium.A few vancomycin-resistant strains were identified in both E.faecalis and E.faecium.The prevalence of penicillin-susceptible Streptococcus pneumoniae was 93.1％ in the isolates from children and and 95.9％ in the isolates from adults.The resistance rate to carbapenems was lower than 15.0％ for most Enterobacterales species except for Klebsiella,22.5％ and 23.6％ of which were resistant to imipenem and meropenem,respectively .Most Enterobacterales isolates were highly susceptible to tigecycline,colistin and polymyxin B,with resistance rates ranging from 0.6％ to 10.0％.The resistance rate to imipenem and meropenem was 21.9％ and 17.4％ for Pseudomonas aeruginosa,respectively,and 67.5％ and 68.1％ for Acinetobacter baumannii,respectively.Conclusions Increasing resistance to the commonly used antimicrobial agents is still observed in clinical bacterial isolates.However,the prevalence of important crabapenem-resistant organisms such as crabapenem-resistant K.pneumoniae,P.aeruginosa,and A.baumannii showed a slightly decreasing trend.This finding suggests that strengthening bacterial resistance surveillance and multidisciplinary linkage are important for preventing the occurrence and development of bacterial resistance.

Objective:To analyze the spontaneous reports on adverse drug reaction (ADR) in a hospital and to mine the risk signals of drug that might be associated with cardiac and neurological ADRs in pregnant women.Methods:The ADR reports in the database of China Hospital Pharmacovigilance System reported by Fujian Maternal and Child Health Hospital from January 1st, 2000 to December 31st, 2022 was downloaded. ADR reports about pregnancy women were collected, and the proportions and clinical manifestations of ADRs classified as "cardiac disorders" and "nervous system disorders" according to systems and organs were analyzed by descriptive statistic method. Data mining was conducted on drugs that might be associated with cardiac disorders and nervous system disorders in ADR reports using the reporting odds ratio (ROR) method and Bayesian confidence propagation neural network (BCPNN) method. The definition of risk signals in ROR method was the number of adverse reaction/event reports on the target drug (a) ≥3, and the lower limit of the 95% confidence interval ( CI) of ROR >1. The definition of risk signals in BCPNN method was the information component minus twice the standard deviation ( IC-2 SD) >0. When the calculation results of an adverse reaction/event was in accordance with above-mentioned conditions in both methods, a suspected drug risk signal was determined. Results:A total of 783 ADR reports about pregnancy women were included in the analysis. Ninety-four reports (12.0%) were about cardiac disorders, mainly manifested as palpitations; 121 reports (15.5%) were about nervous system disorders, mainly characterized by trembling and dizziness. These ADRs of cardiac disorders and nervous system disorders often occurred in the third trimester of pregnancy. Through the ROR and BCPNN methods, results showed that ritodrine hydrochloride injection (a=61, ROR=14.64, the lower limit of 95 %CI=9.08; IC-2 SD=1.36) and ritodrine hydrochloride tablets (a=24, ROR=8.34, the lower limit of 95 %CI=4.64; IC-2 SD=1.10) were risk signals of drug leading to cardiac disorders during pregnancy, while magnesium sulfate injection (a=37, ROR=6.66, the lower limit of 95 %CI=4.10; IC-2 SD=0.98) and ritodrine hydrochloride injection (a=45, ROR=3.72, the lower limit of 95 %CI=2.44; IC-2 SD=0.56) were risk signals of drug leading to nervous system disorders during pregnancy. Conclusion:Ritodrine and magnesium sulfate may be associated with cardiac and nervous system ADR in women during pregnancy, which should arouse clinical vigilance.

Objective To monitor the susceptibility of clinical isolates to antimicrobial agents in healthcare facilities in major regions of China in 2023.Methods Clinical isolates collected from 73 hospitals across China were tested for antimicrobial susceptibility using a unified protocol based on disc diffusion method or automated testing systems.Results were interpreted using the 2023 Clinical & Laboratory Standards Institute (CLSI) breakpoints.Results A total of 445199 clinical isolates were collected in 2023,of which 29.0％ were gram-positive and 71.0％ were gram-negative.The prevalence of methicillin-resistant strains in Staphylococcus aureus,Staphylococcus epidermidis and other coagulase-negative Staphylococcus species (excluding Staphylococcus pseudintermedius and Staphylococcus schleiferi) (MRSA,MRSE and MRCNS) was 29.6％,81.9％ and 78.5％,respectively.Methicillin-resistant strains showed significantly higher resistance rates to most antimicrobial agents than methicillin-susceptible strains (MSSA,MSSE and MSCNS).Overall,92.9％ of MRSA strains were susceptible to trimethoprim-sulfamethoxazole and 91.4％ of MRSE strains were susceptible to rifampicin.No vancomycin-resistant strains were found.Enterococcus faecalis had significantly lower resistance rates to most antimicrobial agents tested than Enterococcus faecium.A few vancomycin-resistant strains were identified in both E.faecalis and E.faecium.The prevalence of penicillin-susceptible Streptococcus pneumoniae was 93.1％ in the isolates from children and and 95.9％ in the isolates from adults.The resistance rate to carbapenems was lower than 15.0％ for most Enterobacterales species except for Klebsiella,22.5％ and 23.6％ of which were resistant to imipenem and meropenem,respectively .Most Enterobacterales isolates were highly susceptible to tigecycline,colistin and polymyxin B,with resistance rates ranging from 0.6％ to 10.0％.The resistance rate to imipenem and meropenem was 21.9％ and 17.4％ for Pseudomonas aeruginosa,respectively,and 67.5％ and 68.1％ for Acinetobacter baumannii,respectively.Conclusions Increasing resistance to the commonly used antimicrobial agents is still observed in clinical bacterial isolates.However,the prevalence of important crabapenem-resistant organisms such as crabapenem-resistant K.pneumoniae,P.aeruginosa,and A.baumannii showed a slightly decreasing trend.This finding suggests that strengthening bacterial resistance surveillance and multidisciplinary linkage are important for preventing the occurrence and development of bacterial resistance.