With the development of information technology, the massive growth of pharmaceutical electronic data and the significant increase in the reports of drug adverse event reports have brought great challenges to pharmacovigilance research. Data mining techniques can automatically extract the risk signals of adverse drug reaction from real-world data. Therefore, efficient data mining of massive adverse event reporting is a necessary measure to realize the automatic detection of adverse drug reactions. By introducing the current major large-scale adverse drug event reporting databases and related data mining methods, this study reviews the application and limitations of adverse drug reaction data mining technology in pharmacovigilance, which provides reference for pharmacovigilance-related institutions and researchers.

Objective:To evaluate whether index of microcirculatory resistance(IMR)is associated with left ventricular(LV)remodeling in acute anterior ST elevation myocardial infarction(STEMI)pa-tients undergoing primary percutaneous coronary intervention(PPCI).Methods:This was a single-center retrospective cohort study.The patients with first anterior STEMI who received PPCI from January 2014 to August 2017 in Peking University Third Hospital was enrolled.After PPCI,IMR was measured immediately by using pressure/temperature guidewire.The success rate of IMR measurement was 100％.Also we collected some related clinical data from the medical records and laboratory results.Infarct size[assessed as creatine kinase(CK)peak],echocardiography at baseline and 1 year follow-up were as-sessed.LV adverse remodeling(LVAR)was defined as ≥20％increase in LV end-diastolic volume(LVEDV).Results:A total of forty-three patients were enrolled,with an average age of(58.7±12.4)years.The patients were divided into two groups as IMR ≤25 and IMR＞25 by normal values recommen-ded by previous literature.Compared with IMR ≤25 group,IMR＞25 group had a higher percentage of initial thrombolysis in myocardial infraction(TIMI)grade 0(95.7％vs.65.0％,P=0.029),higher serum CK peak value[4 090(383,15 833)vs.1 580(396,5 583),P=0.004].The IMR＞25 group suffered higher rates of ventricular aneurysm(30.4％vs.5.0％,P=0.021).There was no difference in LVEDV[(111.0±18.8)mL vs.(115.0±23.6)mL,P=0.503]between the two groups 1 day after MI,but after 1 year,LVEDV in IMR＞25 group was significantly higher than in IMR≤25 group[(141.5± 33.7)mLvs.(115.9±27.9)mL,P=0.018].The incidence of LVAR was more significant in IMR＞25 group(47.4％vs.11.8％,P=0.024).Binary Logistics regression showed that IMR[B=0.079,exp(B)(95％CI)=1.082(1.018-1.149),P=0.011]and serum triglyceride level[B=1.610,exp(B)(95％CI)=5.005(1.380-18.152),P=0.014]were the predictors of LVAR 1 year after MI.IMR had a good predictive value for LVAR 1 year after MI[area under the curve(AUC)=0.749,P=0.019],IMR＞29 was a good cutoff value with sensitivity 81.8％and specificity 68.0％.Conclusion:Our study elaborates that immediate measurement of IMR after PPCI in patients with STEMI can reflect the microvas-cular function.And IMR could be used as a quantitative biomarker to predict LVAR after STEMI.

Objective:To compare Al 18F-1, 4, 7-trizacyclononane-1, 4, 7-triacetic acid (NOTA)-fibroblast activation protein inhibitor (FAPI)-04 PET/CT with 18F-FDG PET/CT in the evaluation of patients with initial gastric cancer. Methods:Twenty patients (13 males, 7 females, age: 27-77 years) with histologically proven gastric cancer were recruited prospectively between March 2021 and July 2022 in the First Affiliated Hospital of Zhengzhou University. Each patient underwent both 18F-FDG and Al 18F-NOTA-FAPI-04 PET/CT within one week. SUV max, tumor background ratio (TBR) and positive detection rate of the two methods were compared (Wilcoxon signed rank sum test, McNemar χ2 test). Results:Al 18F-NOTA-FAPI-04 showed higher SUV max and TBR than those of 18F-FDG in primary tumors (10.2(8.0, 13.7) vs 5.2(3.3, 7.7), z=-3.47, P=0.001; 7.6(5.6, 10.3) vs 2.4(1.8, 3.0), z=-3.85, P<0.001). For the detection of primary gastric cancer, the positive detection rate of Al 18F-NOTA-FAPI-04 PET/CT showed the trend of being higher than that of 18F-FDG PET/CT (95%(19/20) and 75%(15/20); χ2=2.25, P=0.125). For assessing lymph node metastasis, the detection rate of Al 18F-NOTA-FAPI-04 PET/CT was higher than that of 18F-FDG PET/CT (78.9%(101/128) vs 64.8%(83/128); χ2=13.47, P<0.001). The SUV max and TBR of Al 18F-NOTA-FAPI-04 in lymph node were higher than those of 18F-FDG (5.3(3.5, 9.2) vs 2.8(1.8, 4.7), z=-7.31, P<0.001; 4.6(2.6, 6.5) vs 1.7(1.0, 3.0), z=-8.44, P<0.001). For the detection of peritoneal carcinomatosis, Al 18F-NOTA-FAPI-04 PET/CT showed higher peritoneal cancer index (PCI), SUV max, and TBR compared to 18F-FDG PET/CT (PCI: 12.0(3.0, 29.8) vs 5.5(0.5, 17.5), z=-2.22, P=0.026; SUV max: 8.2(4.4, 12.5) vs 2.7(1.9, 4.0); z=-2.52, P=0.012; TBR: 5.1(2.9, 13.3) vs 1.1(0.9, 2.0); z=-2.52, P=0.012). Conclusion:Al 18F-NOTA-FAPI-04 PET/CT outperforms 18F-FDG PET/CT in primary and metastatic lesions of gastric cancer and might be a potential novel modality for imaging patients with gastric cancer.

Objective To explore the changes and significane of USP20 and HIF-α expression in breast cancer.Methods Following transfection of shRNA-USP20 lentivirus into breast cancer MDA-MB-231 cells,the gene and protein expression levels of USP20 were detected using fluorescence quantitative PCR and Western Blot.Subsequently,the overexpression of USP20 was observed to determine its effect on HIF-α expression.Similarly,siRNA-USP20 was used to knock down USP20 in breast cancer MDA-MB-231 cells,followed by detection of gene and protein expression levels using fluorescence quantitative PCR and Western Blot.The subsequent changes in HIF-α expression were then examined.Rusults The positive expression rates of USP20 and HIF-α in breast cancer tissues were 69.6%and 46.83%,respectively,while they were negatively expressed in the adjacent normal tissues,with statistically significant differences(P＜0.01).The positive expressions of USP20 and HIF-α were predomi-nantly observed in the cytoplasm of breast cancer tissue,with a smaller amount present in the nucleus.There was a significant positive correlation between USP20 and HIF-α in breast cancer.Following transfection of shRNA-USP20 lentivirus into MDA-MB-231 cells,both the protein and gene expression levels of USP20 significantly increased(P＜0.01).Over-expression of USP20 did not affect HIF-α mRNA levels but led to a significant increase in HIF-α protein expression(P＜0.01).Conversely,siRNA-USP20 interference resulted in a significant decrease in both the protein and gene expression levels of USP20(P＜0.01),without affecting HIF-α mRNA levels;however,it caused a notable reduction in HIF-α protein expression(P＜0.01).Conclusion The expression of USP20 exhib-ited a significant positive correlation with HIF-α in breast cancer.Overexpression of USP20 led to a substantial increase in HIF-α protein expression,while knock-down of the USP20 gene resulted in a significant decrease in HIF-α protein levels.Therefore,it can be inferred that USP20 may exert its influence on the development of breast cancer through modulation of HIF-α expression,thereby providing crucial experimental evidence for clinical treat-ment,prognosis,and further investigations.

Objective:To understand the monkeypox knowledge awareness, risk perception and vaccination intention in men who have sex with men (MSM) in five cities in northeast China.Methods:A cross-sectional study was conducted by using electronic questionnaire in MSM selected by convenience sampling in five cities in northeast China (Shenyang, Panjin, Changchun, Harbin and Jiamusi) from June 28 to July 8, 2023 by local centers for disease control and prevention and MSM communities. The sample size was estimated to be 220. Information about their demographics, monkeypox-related knowledge awareness, perceived concern about epidemic risk perception, and monkeypox vaccination intention were collected. Logistic regression model was used to analyze related factors for MSM's monkeypox vaccination intention.Results:In 355 MSM, 63.9% (227/355) had monkeypox vaccination intentions, and 55.5% (197/355) had high awareness of monkeypox related knowledge with a mean knowledge awareness score of 3.7±1.5. MSM with education level of high-school and above (a OR=1.93, 95% CI:1.01-3.69), higher knowledge awareness score (a OR=1.19, 95% CI:1.02-1.40) and higher risk perception of monkeypox infection (a OR=1.82, 95% CI:1.15-2.88), were more willing to receive monkeypox vaccination. The main reasons for willingness to receive monkeypox vaccine were preventing monkeypox (86.3%, 196/227) and worrying about appearance being affected (62.1%, 141/227). The main reasons for unwillingness for the vaccination included concerns about vaccine safety (53.1%, 68/128), clinical progression of AIDS being affected (46.1%, 59/128) and efficacy of antiretroviral therapy being affected (44.5%, 57/128). Conclusions:The levels of knowledge awareness and vaccine intentions still need to be improved among MSM in five cities of northeast China. It is necessary to improve the awareness of monkeypox and intention of monkeypox vaccination, promote protected sex behavior and self-assessment of infection risk, reduce vaccine hesitancy and increase monkeypox vaccination intention in MSM in 5 cities in northeast China.

Objective To investigate the relationship between the therapeutic effect of anti-vascular endothelial growth factor(VEGF)and cytokines in aqueous humor in patients with diabetic retinopathy(DR).Methods From July 2023 to December 2023,50 DR patients(56 eyes)who were treated with anti-VEGF drugs in the Department of Ophthal-mology,the Third Affiliated Hospital of Xinxiang Medical University were included in this study.The patients were divided into the diabetic macular edema(DME)group(30 patients,36 eyes)and the proliferative DR(PDR)group(20 patients,20 eyes).Patients in the DME group received an intravitreal injection of aflibercept once a month for three consecutive times,with aqueous humor extracted before each injection.Patients in the PDR group received an intravitreal injection of aflibercept one week before vitrectomy,with aqueous humor extracted before injection and during vitrectomy,respective-ly.The concentrations of vascular endothelial growth factor A(VEGF-A),placental growth factor(PLGF),interleukin(IL)-1β,IL-23,IL-17A,and tumor necrosis factor-α(TNF-α)in the aqueous humor were detected using the Luminex as-say.Before injection therapy,all patients underwent best corrected visual acuity(BCVA)and central macular thickness(CMT)examinations,and their correlations with cytokine concentrations in DR patients before injection therapy were ana-lyzed.Results Compared to before injection therapy,the concentrations of VEGF-A,PLGF,and IL-23 in the aqueous humor of patients in the DME group decreased significantly after treatment(all P＜0.05);additionally,the CMT de-creased,and the BCVA increased(both P＜0.05).After injection therapy,the concentrations of VEGF,PLGF,IL-1β,IL-23,IL-17A,and TNF-α in the aqueous humor of patients in the PDR group significantly decreased compared to before injec-tion therapy(all P＜0.05).Before injection therapy,the levels of VEGF-A,PLGF,and IL-23 in the aqueous humor of pa-tients in the DME group were higher than those in the PDR group,and the differences were statistically significant(all P＜0.05).The correlation analysis results showed that before injection therapy,VEGF was negatively correlated with BCVA(r=-0.767,P=0.004)and was positively correlated with CMT(r=0.662,P=0.019)and IL-23(r=0.765,P=0.004)in the DME group.There was no correlation between the cytokines in the aqueous humor of patients in the PDR group be-fore injection therapy(all P＞0.05).Conclusion Changes in the concentration of VEGF-A,PLGF,and IL-23 are closely related to the occurrence and development of DR.Anti-VEGF treatment can improve BCVA and decrease CMT in DME pa-tients.The expression level of IL-23 in aqueous humor can serve as a predictive factor for the anti-VEGF efficacy in DR pa-tients,providing new targets for early diagnosis and treatment of DR.

Objective To monitor the susceptibility of clinical isolates to antimicrobial agents in tertiary hospitals in major regions of China in 2022.Methods Clinical isolates from 58 hospitals in China were tested for antimicrobial susceptibility using a unified protocol based on disc diffusion method or automated testing systems.Results were interpreted using the 2022 Clinical &Laboratory Standards Institute(CLSI)breakpoints.Results A total of 318 013 clinical isolates were collected from January 1,2022 to December 31,2022,of which 29.5％were gram-positive and 70.5％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)was 28.3％,76.7％and 77.9％,respectively.Overall,94.0％of MRSA strains were susceptible to trimethoprim-sulfamethoxazole and 90.8％of MRSE strains were susceptible to rifampicin.No vancomycin-resistant strains were found.Enterococcus faecalis showed 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 94.2％in the isolates from children and 95.7％in the isolates from adults.The resistance rate to carbapenems was lower than 13.1％in most Enterobacterales species except for Klebsiella,21.7％-23.1％of which were resistant to carbapenems.Most Enterobacterales isolates were highly susceptible to tigecycline,colistin and polymyxin B,with resistance rates ranging from 0.1％to 13.3％.The prevalence of meropenem-resistant strains decreased from 23.5％in 2019 to 18.0％in 2022 in Pseudomonas aeruginosa,and decreased from 79.0％in 2019 to 72.5％in 2022 in Acinetobacter baumannii.Conclusions The resistance of clinical isolates to the commonly used antimicrobial agents is still increasing in tertiary hospitals.However,the prevalence of important carbapenem-resistant organisms such as carbapenem-resistant K.pneumoniae,P.aeruginosa,and A.baumannii showed a downward trend in recent years.This finding suggests that the strategy of combining antimicrobial resistance surveillance with multidisciplinary concerted action works well in curbing the spread of resistant bacteria.

Objective To investigate the distribution and antimicrobial resistance profiles of the common pathogens isolated from urine from 2015 to 2021 in the CHINET Antimicrobial Resistance Surveillance Program.Methods The bacterial strains were isolated from urine and identified routinely in 51 hospitals across China in the CHINET Antimicrobial Resistance Surveillance Program from 2015 to 2021.Antimicrobial susceptibility was determined by Kirby-Bauer method,automatic microbiological analysis system and E-test according to the unified protocol.Results A total of 261 893 nonduplicate strains were isolated from urine specimen from 2015 to 2021,of which gram-positive bacteria accounted for 23.8％(62 219/261 893),and gram-negative bacteria 76.2％(199 674/261 893).The most common species were E.coli(46.7％),E.faecium(10.4％),K.pneumoniae(9.8％),E.faecalis(8.7％),P.mirabilis(3.5％),P.aeruginosa(3.4％),SS.agalactiae(2.6％),and E.cloacae(2.1％).The strains were more frequently isolated from inpatients versus outpatients and emergency patients,from females versus males,and from adults versus children.The prevalence of ESBLs-producing strains in E.coli,K.pneumoniae and P.mirabilis was 53.2％,52.8％and 37.0％,respectively.The prevalence of carbapenem-resistant strains in E.coli,K.pneumoniae,P.aeruginosa and A.baumannii was 1.7％,18.5％,16.4％,and 40.3％,respectively.Lower than 10％of the E.faecalis isolates were resistant to ampicillin,nitrofurantoin,linezolid,vancomycin,teicoplanin and fosfomycin.More than 90％of the E.faecium isolates were ressitant to ampicillin,levofloxacin and erythromycin.The percentage of strains resistant to vancomycin,linezolid or teicoplanin was＜2％.The E.coli,K.pneumoniae,P.aeruginosa and A.baumannii strains isolated from ICU inpatients showed significantly higher resistance rates than the corresponding strains isolated from outpatients and non-ICU inpatients.Conclusions E.coli,Enterococcus and K.pneumoniae are the most common pathogens in urinary tract infection.The bacterial species and antimicrobial resistance of urinary isolates vary with different populations.More attention should be paid to antimicrobial resistance surveillance and reduce the irrational use of antimicrobial agents.

Objective To understand the distribution and changing resistance profiles of clinical isolates of Enterococcus in hospitals across China from 2015 to 2021.Methods Antimicrobial susceptibility testing was conducted for the clinical isolates of Enterococcus according to the unified protocol of CHINET program by automated systems,Kirby-Bauer method,or E-test strip.The results were interpreted according to the Clinical & Laboratory Standards Institute(CLSI)breakpoints in 2021.WHONET 5.6 software was used for statistical analysis.Results A total of 124 565 strains of Enterococcus were isolated during the 7-year period,mainly including Enterococcus faecalis(50.7％)and Enterococcus faecalis(41.5％).The strains were mainly isolated from urinary tract specimens(46.9％±2.6％),and primarily from the patients in the department of internal medicine,surgery and ICU.E.faecium and E.faecalis strains showed low level resistance rate to vancomycin,teicoplanin and linezolid(≤3.6％).The prevalence of vancomycin-resistant E.faecalis and E.faecium was 0.1％and 1.3％,respectively.The prevalence of linezolid-resistant E.faecalis increased from 0.7％in 2015 to 3.4％in 2021,while the prevalence of linezolid-resistant E.faecium was 0.3％.Conclusions The clinical isolates of Enterococcus were still highly susceptible to vancomycin,teicoplanin,and linezolid,evidenced by a low resistance rate.However,the prevalence of linezolid-resistant E.faecalis was increasing during the 7-year period.It is necessary to strengthen antimicrobial resistance surveillance to effectively identify the emergence of antibiotic-resistant bacteria and curb the spread of resistant pathogens.

Objective To examine the changing antimicrobial resistance profile of Enterobacter spp.isolates in 53 hospitals across China from 2015 t0 2021.Methods The clinical isolates of Enterobacter spp.were collected from 53 hospitals across China during 2015-2021 and tested for antimicrobial susceptibility using Kirby-Bauer method or automated testing systems according to the CHINET unified protocol.The results were interpreted according to the breakpoints issued by the Clinical & Laboratory Standards Institute(CLSI)in 2021(M100 31st edition)and analyzed with WHONET 5.6 software.Results A total of 37 966 Enterobacter strains were isolated from 2015 to 2021.The proportion of Enterobacter isolates among all clinical isolates showed a fluctuating trend over the 7-year period,overall 2.5％in all clinical isolates amd 5.7％in Enterobacterale strains.The most frequently isolated Enterobacter species was Enterobacter cloacae,accounting for 93.7％(35 571/37 966).The strains were mainly isolated from respiratory specimens(44.4±4.6)％,followed by secretions/pus(16.4±2.3)％and urine(16.0±0.9)％.The strains from respiratory samples decreased slightly,while those from sterile body fluids increased over the 7-year period.The Enterobacter strains were mainly isolated from inpatients(92.9％),and only(7.1±0.8)％of the strains were isolated from outpatients and emergency patients.The patients in surgical wards contributed the highest number of isolates(24.4±2.9)％compared to the inpatients in any other departement.Overall,≤ 7.9％of the E.cloacae strains were resistant to amikacin,tigecycline,polymyxin B,imipenem or meropenem,while ≤5.6％of the Enterobacter asburiae strains were resistant to these antimicrobial agents.E.asburiae showed higher resistance rate to polymyxin B than E.cloacae(19.7％vs 3.9％).Overall,≤8.1％of the Enterobacter gergoviae strains were resistant to tigecycline,amikacin,meropenem,or imipenem,while 10.5％of these strains were resistant to polycolistin B.The overall prevalence of carbapenem-resistant Enterobacter was 10.0％over the 7-year period,but showing an upward trend.The resistance profiles of Enterobacter isolates varied with the department from which they were isolated and whether the patient is an adult or a child.The prevalence of carbapenem-resistant E.cloacae was the highest in the E.cloacae isolates from ICU patients.Conclusions The results of the CHINET Antimicrobial Resistance Surveillance Program indicate that the proportion of Enterobacter strains in all clinical isolates fluctuates slightly over the 7-year period from 2015 to 2021.The Enterobacter strains showed increasing resistance to multiple antimicrobial drugs,especially carbapenems over the 7-year period.