Objective:To compare the antiplatelet effects of vicagrel and clopidogrel in patients with different cytochrome P450 (CYP) 2C19 genotypes.Methods:This is a post-hoc analysis of a phase Ⅱ clinical trial of vicagrel, which included patients with coronary heart disease who underwent percutaneous coronary intervention from August 2018 to June 2019 in 18 centers. Patients were categorized based on the presence of CYP 2C19 *2 or *3 loss-of-function (LOF) alleles into LOF carrier group ( n=111) and non-LOF carrier group ( n=90). Each group included patients received vicagrel 5 mg, 6 mg, 7.5 mg, or clopidogrel 75 mg for 28 days per study protocol. P2Y 12 reaction units (PRU) were measured using VerifyNow at baseline, 6 to 8 hours after loading dose, 7 to 10 days after randomization, and 28 days after randomization and the percentage inhibition of platelet aggregation (%IPA) was calculated. The primary endpoint was %IPA on day 28. Within the patients from the General Hospital of Northern Theater Command, 8 to 12 patients in each study arms were enrolled in a prespecified pharmacokinetic sub-study, measuring the time to reach maximum plasma concentration (T max), peak plasma concentration (C max), and area under the plasma concentration-time curve (AUC). Results:Among 201 patients, the age was (58.8±8.5) years, and 139 (69.2%) were male. In non-LOF carriers, there was no significant differences in PRU values and %IPA between the vicagrel 5 mg, 6 mg, 7 mg, and clopidogrel groups at all time points (all P>0.05). In LOF carriers, %IPA was significantly higher in the vicagrel-treated groups than in the clopidogrel group at 6-8 hours after loading dose (22.9 (14.2, 31.5)% vs. 19.8 (11.0, 28.6)% vs. 29.5 (20.9, 38.0)% vs. 12.9 (3.9, 21.9)%, P=0.038) and 7-10 days after randomization (22.4 (14.2, 30.5)% vs. 34.4 (26.1, 42.6)% vs. 39.8 (31.8, 47.9)% vs. 24.7 (16.3, 33.2)%, P=0.001), with a trend towards higher %IPA in the vicagrel-treated groups at day 28 (30.4 (21.3, 39.6)% vs. 36.5 (27.2, 45.7)% vs. 40.8 (31.8, 49.8)% vs. 30.7(21.2, 40.2)%, P=0.056). Pharmacokinetic results of 35 patients showed that the C max and AUC of the active metabolite M15-2 of vicagrel was similar to that of clopidogrel in non-LOF carriers, but AUC between vicagrel 5 mg, 6 mg, 7 mg and clopidogrel were significantly different in LOF carriers ((5.6±0.6) h·μg -1·L -1 vs. (6.8±2.7) h·μg -1·L -1 vs. (9.2±3.3) h·μg -1·L -1 vs. (4.2±1.9) h·μg -1·ml -1, P=0.020). Conclusion:Vicagrel and clopidogrel have similar antiplatelet effects in non-LOF carriers, but vicagrel exhibits superior antiplatelet effects in LOF carriers.

Background: Twenty-four-hour urinary free cortisol (UFC) measurement is the initial diagnostic test for Cushing’s syndrome (CS). We compared UFC determination by both direct and extraction immunoassays using Abbott Architect, Siemens Atellica Solution, and Beckman DxI800 with liquid chromatography-tandem mass spectrometry (LC-MS/MS). In addition, we evaluated the value of 24-hr UFC measured by six methods for diagnosing CS. Methods: Residual 24-hr urine samples of 94 CS and 246 non-CS patients were collected.A laboratory-developed LC-MS/MS method was used as reference. UFC was measured by direct assays (D) using Abbott, Siemens, and Beckman platforms and by extraction assays (E) using Siemens and Beckman platforms. Method was compared using Passing–Bablok regression and Bland–Altman plot analyses. Cut-off values for the six assays and corresponding sensitivities and specificities were calculated by ROC analysis. Results: Abbott-D, Beckman-E, Siemens-E, and Siemens-D showed strong correlations with LC-MS/MS (Spearman coefficient r = 0.965, 0.922, 0.922, and 0.897, respectively), while Beckman-D showed weaker correlation (r = 0.755). All immunoassays showed proportionally positive bias. The areas under the curve were 0.975 for Abbott-D, 0.972 for LCMS/MS, 0.966 for Siemens-E, 0.948 for Siemens-D, 0.955 for Beckman-E, and 0.877 for Beckman-D. The cut-off values varied significantly (154.8–1,321.5 nmol/24 hrs). Assay sensitivity and specificity ranged from 76.1% to 93.2% and from 93.0% to 97.1%, respectively. Conclusions Commercially available immunoassays for measuring UFC show different levels of analytical consistency compared to LC-MS/MS. Abbott-D, Siemens-E, and Beckman-E have high diagnostic accuracy for CS.

Endodontic diseases are a kind of chronic infectious oral disease.Common endodontic treatment concepts are based on the removal of inflamed or necrotic pulp tissue and the replacement by gutta-percha.However,it is very essential for endodontic treatment to debride the root canal system and prevent the root canal system from bacterial reinfection after root canal therapy(RCT).Recent research,encompassing bacterial etiology and advanced imaging techniques,contributes to our understanding of the root canal system's anatomy intricacies and the technique sensitivity of RCT.Success in RCT hinges on factors like patients,infection severity,root canal anatomy,and treatment techniques.Therefore,improving disease management is a key issue to combat endodontic diseases and cure periapical lesions.The clinical difficulty assessment system of RCT is established based on patient conditions,tooth conditions,root canal configuration,and root canal needing retreatment,and emphasizes pre-treatment risk assessment for optimal outcomes.The findings suggest that the presence of risk factors may correlate with the challenge of achieving the high standard required for RCT.These insights contribute not only to improve education but also aid practitioners in treatment planning and referral decision-making within the field of endodontics.

Objective To investigate the potential risk factors for immune checkpoint-related pneumonia(CIP)in non-small cell lung cancer(NSCLC)patients treated with immune checkpoint inhibitors(ICIs),to identify high-risk patients with CIP at an early stage.Methods A total of 728 NSCLC patients treated with ICIs at the First Affiliated Hospital of Zhengzhou University from January 2020 to June 2023 were retrospectively selected,including 47 cases with CIP(CIP group),and 141 matched NSCLC patients without CIP(control group).Clinical data,laboratory tests,and CT images before the first immunotherapy were collected for all patients in two groups.The FACT medical imaging software was utilized for quantitative emphysema assessment in patients'CT scans.Univariate and multivariate logistic regression analyses were conducted to identify the risk factors associated with CIP.Receiver operating characteristic(ROC)curves were plotted to evaluate the predictive value of these factors for CIP occurrence in NSCLC patients.Results Among the 47 CIP patients,40(85.1%)were male,with 25(53.0%)aged between 41 and 65 years.Grade 3 pneumonia according to the Common Terminology Criteria for Adverse Events(CTCAE)was found in 28(59.6%)cases,characterized by a predominant reticular radiographic pattern.Multivariate logistic regression analysis showed that a low albumin level(OR=0.889,95%CI 0.808-0.979,P=0.017),targeted therapy(OR=9.204,95%CI 1.678-50.486,P=0.011),anti-angiogenic therapy(OR=0.056,95%CI 0.020-0.161,P<0.001),and a high percentage of low attenuation area(LAA%)(OR=1.227,95%CI 1.053-1.430,P=0.009)were significant factors influencing CIP occurrence.The combined predictive model using these four factors showed an area under the ROC curve of 0.888(95%CI 0.838-0.939),with a sensitivity of 0.894 and a specificity of 0.801 for predicting CIP in NSCLC patients.Conclusions Low serum albumin,first-line targeted therapy,and high LAA%are identified as risk factors for CIP occurrence,while anti-angiogenic therapy is a protective factor.The predictive model based on these four variables effectively predicts the risk of CIP in NSCLC patients.

This study was aimed at investigating the antimicrobial susceptibility and genomic characteristics of multidrug resistant diarrheagenic Escherichia coli isolated from human and food samples in Henan Province from 2017 to 2022.A total of 101 strains of multidrug resistant diarrheagenic E.coli were subjected to antimicrobial susceptibility testing with the broth di-lution method.Whole genome sequencing was performed to analyze the antimicrobial resistance genes,multilocus sequence typ-ing,and plasmid types.The sequencing data were used to construct a phylogenetic tree based on core genome single-nucleotide polymorphisms(cgSNPs).The isolates showed the highest resistance to ampicillin(87.1％),followed by tetracycline(79.2％)and nalidixic acid(64.4％).The resistance rate to cefotaxime was 38.6％.All 101 strains were classified into 60 STs,among which ST10,ST1491,and ST38 were dominant.Moreover,23 distinct plasmid replicons were identified,among which IncFIB was dominant.Diverse antimicrobial resistance genes(including quinolone,aminoglycoside,β-lactamase,and tetracycline)were identified.Insertion sequences(IS26,IS903B,and ISECP 1)were identified in upstream and downstream analysis of the gene context of the extended-spectrum β-lactamase bla CTX-M-14 and bla CTX-M-55 genes.In conclusion,multidrug resistant diarrhea-genic Escherichia coli isolated from clinical and food samples in Henan Province showed high genetic diversity and high antimi-crobial resistance.The dissemination of blaCTX-M carried by the strains was shown to be associated with the insertion sequence(IS).

Objective:To explore the challenges in the implementation of drug centralized volume-based procurement policies in hospitals and propose corresponding optimization suggestions.Methods:From August to December 2023, a purposive sampling was conducted to select 11 pharmaceutical experts from tertiary hospitals in China for Delphi method. The survey content included " policy recommendations for promoting the acceleration and expansion of national drug centralized procurement and retaining surplus medical insurance funds for centralized procurement" .Results:Survey participants gave feedback on a set of existing problems found in the implementation of drug centralized procurement policies and proposed corresponding optimization methods. Kendall′s W coefficient of the specialist consultation was 0.332( P<0.05), demonstrating good consistency and concentration of the expert opinions. Among the problems, the score of drug supply guarantee was the highest(mean value of importance was 4.45). At the same time, the recommendation of strengthening monitoring and early warning, coordination and dispatch, and effectively ensuring the supply of centralized drug procurement had the highest score and concentration(mean value of importance was 4.91, coefficient of variation was 0.06). Conclusions:Through Delphi method, this study revealed issues and optimization methods in the implementation of drug centralized procurement policies in hospitals. The findings could provide valuable insights for improvements in the pharmaceutical sector and future policy adjustments.

Purpose: This study evaluated the value of contrast-enhanced ultrasonography (CEUS) in the ultrasound-guided microwave ablation (MWA) treatment of symptomatic focal uterine adenomyosis. Methods: This retrospective study was conducted between March 2020 and January 2023, enrolling 52 patients with symptomatic focal uterine adenomyosis who had undergone MWA. All patients were examined with CEUS before and after MWA. The non-perfused volume (NPV) was compared between CEUS and dynamic contrast-enhanced magnetic resonance imaging (DCEMRI) following ablation. Therapeutic efficacy and safety were evaluated at 3-, 6-, and 12-month follow-ups. Additionally, this study explored the correlations between pre-treatment CEUS features and a volume reduction ratio indicating sufficient ablation, defined as 50% or more at the 3-month follow-up. Results: No significant differences in NPV were noted between CEUS and DCE-MRI immediately after MWA and during follow-up (all P>0.05). At the 3-month follow-up, the median VRRs for the uterus and adenomyosis were 33.2% and 63.9%, respectively. Sufficient ablation was achieved in 69.2% (36/52) of adenomyosis cases, while partial ablation was observed in the remaining 30.8% (16/52). The identification of non-enhancing areas on pre-treatment CEUS was associated with sufficient ablation (P=0.016). At the 12-month follow-up, significant decreases were observed in both the uterine and adenomyosis volumes (all P<0.001). Dysmenorrhea and menorrhagia were significantly alleviated at 12 months, and no major complications were encountered. Conclusion CEUS can be used to evaluate the ablation zone of focal adenomyosis that has been treated with MWA, similarly to DCE-MRI. The identification of non-enhancing areas on pretreatment CEUS indicates satisfactory treatment outcomes.

Purpose: This study evaluated the value of contrast-enhanced ultrasonography (CEUS) in the ultrasound-guided microwave ablation (MWA) treatment of symptomatic focal uterine adenomyosis. Methods: This retrospective study was conducted between March 2020 and January 2023, enrolling 52 patients with symptomatic focal uterine adenomyosis who had undergone MWA. All patients were examined with CEUS before and after MWA. The non-perfused volume (NPV) was compared between CEUS and dynamic contrast-enhanced magnetic resonance imaging (DCEMRI) following ablation. Therapeutic efficacy and safety were evaluated at 3-, 6-, and 12-month follow-ups. Additionally, this study explored the correlations between pre-treatment CEUS features and a volume reduction ratio indicating sufficient ablation, defined as 50% or more at the 3-month follow-up. Results: No significant differences in NPV were noted between CEUS and DCE-MRI immediately after MWA and during follow-up (all P>0.05). At the 3-month follow-up, the median VRRs for the uterus and adenomyosis were 33.2% and 63.9%, respectively. Sufficient ablation was achieved in 69.2% (36/52) of adenomyosis cases, while partial ablation was observed in the remaining 30.8% (16/52). The identification of non-enhancing areas on pre-treatment CEUS was associated with sufficient ablation (P=0.016). At the 12-month follow-up, significant decreases were observed in both the uterine and adenomyosis volumes (all P<0.001). Dysmenorrhea and menorrhagia were significantly alleviated at 12 months, and no major complications were encountered. Conclusion CEUS can be used to evaluate the ablation zone of focal adenomyosis that has been treated with MWA, similarly to DCE-MRI. The identification of non-enhancing areas on pretreatment CEUS indicates satisfactory treatment outcomes.

Purpose: This study evaluated the value of contrast-enhanced ultrasonography (CEUS) in the ultrasound-guided microwave ablation (MWA) treatment of symptomatic focal uterine adenomyosis. Methods: This retrospective study was conducted between March 2020 and January 2023, enrolling 52 patients with symptomatic focal uterine adenomyosis who had undergone MWA. All patients were examined with CEUS before and after MWA. The non-perfused volume (NPV) was compared between CEUS and dynamic contrast-enhanced magnetic resonance imaging (DCEMRI) following ablation. Therapeutic efficacy and safety were evaluated at 3-, 6-, and 12-month follow-ups. Additionally, this study explored the correlations between pre-treatment CEUS features and a volume reduction ratio indicating sufficient ablation, defined as 50% or more at the 3-month follow-up. Results: No significant differences in NPV were noted between CEUS and DCE-MRI immediately after MWA and during follow-up (all P>0.05). At the 3-month follow-up, the median VRRs for the uterus and adenomyosis were 33.2% and 63.9%, respectively. Sufficient ablation was achieved in 69.2% (36/52) of adenomyosis cases, while partial ablation was observed in the remaining 30.8% (16/52). The identification of non-enhancing areas on pre-treatment CEUS was associated with sufficient ablation (P=0.016). At the 12-month follow-up, significant decreases were observed in both the uterine and adenomyosis volumes (all P<0.001). Dysmenorrhea and menorrhagia were significantly alleviated at 12 months, and no major complications were encountered. Conclusion CEUS can be used to evaluate the ablation zone of focal adenomyosis that has been treated with MWA, similarly to DCE-MRI. The identification of non-enhancing areas on pretreatment CEUS indicates satisfactory treatment outcomes.

Purpose: This study evaluated the value of contrast-enhanced ultrasonography (CEUS) in the ultrasound-guided microwave ablation (MWA) treatment of symptomatic focal uterine adenomyosis. Methods: This retrospective study was conducted between March 2020 and January 2023, enrolling 52 patients with symptomatic focal uterine adenomyosis who had undergone MWA. All patients were examined with CEUS before and after MWA. The non-perfused volume (NPV) was compared between CEUS and dynamic contrast-enhanced magnetic resonance imaging (DCEMRI) following ablation. Therapeutic efficacy and safety were evaluated at 3-, 6-, and 12-month follow-ups. Additionally, this study explored the correlations between pre-treatment CEUS features and a volume reduction ratio indicating sufficient ablation, defined as 50% or more at the 3-month follow-up. Results: No significant differences in NPV were noted between CEUS and DCE-MRI immediately after MWA and during follow-up (all P>0.05). At the 3-month follow-up, the median VRRs for the uterus and adenomyosis were 33.2% and 63.9%, respectively. Sufficient ablation was achieved in 69.2% (36/52) of adenomyosis cases, while partial ablation was observed in the remaining 30.8% (16/52). The identification of non-enhancing areas on pre-treatment CEUS was associated with sufficient ablation (P=0.016). At the 12-month follow-up, significant decreases were observed in both the uterine and adenomyosis volumes (all P<0.001). Dysmenorrhea and menorrhagia were significantly alleviated at 12 months, and no major complications were encountered. Conclusion CEUS can be used to evaluate the ablation zone of focal adenomyosis that has been treated with MWA, similarly to DCE-MRI. The identification of non-enhancing areas on pretreatment CEUS indicates satisfactory treatment outcomes.