Background: s/Aims: Non-invasive models stratifying clinically significant portal hypertension (CSPH) are limited. Herein, we developed a new non-invasive model for predicting CSPH in patients with compensated cirrhosis and investigated whether carvedilol can prevent hepatic decompensation in patients with high-risk CSPH stratified using the new model. Methods: Non-invasive risk factors of CSPH were identified via systematic review and meta-analysis of studies involving patients with hepatic venous pressure gradient (HVPG). A new non-invasive model was validated for various performance aspects in three cohorts, i.e., a multicenter HVPG cohort, a follow-up cohort, and a carvediloltreating cohort. Results: In the meta-analysis with six studies (n=819), liver stiffness measurement and platelet count were identified as independent risk factors for CSPH and were used to develop the new “CSPH risk” model. In the HVPG cohort (n=151), the new model accurately predicted CSPH with cutoff values of 0 and –0.68 for ruling in and out CSPH, respectively. In the follow-up cohort (n=1,102), the cumulative incidences of decompensation events significantly differed using the cutoff values of <–0.68 (low-risk), –0.68 to 0 (medium-risk), and >0 (high-risk). In the carvediloltreated cohort, patients with high-risk CSPH treated with carvedilol (n=81) had lower rates of decompensation events than non-selective beta-blockers untreated patients with high-risk CSPH (n=613 before propensity score matching [PSM], n=162 after PSM). Conclusions Treatment with carvedilol significantly reduces the risk of hepatic decompensation in patients with high-risk CSPH stratified by the new model.

Background: s/Aims: Non-invasive models stratifying clinically significant portal hypertension (CSPH) are limited. Herein, we developed a new non-invasive model for predicting CSPH in patients with compensated cirrhosis and investigated whether carvedilol can prevent hepatic decompensation in patients with high-risk CSPH stratified using the new model. Methods: Non-invasive risk factors of CSPH were identified via systematic review and meta-analysis of studies involving patients with hepatic venous pressure gradient (HVPG). A new non-invasive model was validated for various performance aspects in three cohorts, i.e., a multicenter HVPG cohort, a follow-up cohort, and a carvediloltreating cohort. Results: In the meta-analysis with six studies (n=819), liver stiffness measurement and platelet count were identified as independent risk factors for CSPH and were used to develop the new “CSPH risk” model. In the HVPG cohort (n=151), the new model accurately predicted CSPH with cutoff values of 0 and –0.68 for ruling in and out CSPH, respectively. In the follow-up cohort (n=1,102), the cumulative incidences of decompensation events significantly differed using the cutoff values of <–0.68 (low-risk), –0.68 to 0 (medium-risk), and >0 (high-risk). In the carvediloltreated cohort, patients with high-risk CSPH treated with carvedilol (n=81) had lower rates of decompensation events than non-selective beta-blockers untreated patients with high-risk CSPH (n=613 before propensity score matching [PSM], n=162 after PSM). Conclusions Treatment with carvedilol significantly reduces the risk of hepatic decompensation in patients with high-risk CSPH stratified by the new model.

Background: s/Aims: Non-invasive models stratifying clinically significant portal hypertension (CSPH) are limited. Herein, we developed a new non-invasive model for predicting CSPH in patients with compensated cirrhosis and investigated whether carvedilol can prevent hepatic decompensation in patients with high-risk CSPH stratified using the new model. Methods: Non-invasive risk factors of CSPH were identified via systematic review and meta-analysis of studies involving patients with hepatic venous pressure gradient (HVPG). A new non-invasive model was validated for various performance aspects in three cohorts, i.e., a multicenter HVPG cohort, a follow-up cohort, and a carvediloltreating cohort. Results: In the meta-analysis with six studies (n=819), liver stiffness measurement and platelet count were identified as independent risk factors for CSPH and were used to develop the new “CSPH risk” model. In the HVPG cohort (n=151), the new model accurately predicted CSPH with cutoff values of 0 and –0.68 for ruling in and out CSPH, respectively. In the follow-up cohort (n=1,102), the cumulative incidences of decompensation events significantly differed using the cutoff values of <–0.68 (low-risk), –0.68 to 0 (medium-risk), and >0 (high-risk). In the carvediloltreated cohort, patients with high-risk CSPH treated with carvedilol (n=81) had lower rates of decompensation events than non-selective beta-blockers untreated patients with high-risk CSPH (n=613 before propensity score matching [PSM], n=162 after PSM). Conclusions Treatment with carvedilol significantly reduces the risk of hepatic decompensation in patients with high-risk CSPH stratified by the new model.

INTRODUCTION: Trastuzumab deruxtecan (T-DXd) has revolutionised treatment for metastatic breast cancer (MBC). While effective, its high cost and toxicities, such as fatigue and nausea, pose challenges. METHOD: Medical records from the Joint Breast Cancer Registry in Singapore were used to study MBC patients treated with T-DXd (February 2021-June 2024). This study was conducted to address whether reducing dose intensity and density may have an adverse effect on treatment outcomes. RESULTS: Eighty-seven MBC patients were treated with T-DXd, with a median age of 59 years. At the time of data cutoff, 32.1% of patients were still receiving T-DXd. Over half (54%) of the patients received treatment with an initial relative dose intensity (RDI) of <;85%. Overall median real-world progression-free survival (rwPFS) was 8.1 months. rwPFS was similar between RDI groups (<85%: 8.7 months, <85%: 8.1 months, P=0.62). However, human epidermal growth receptor 2 (HER2)-positive patients showed significantly better rwPFS outcomes compared to HER2-low patients (8.8 versus 2.5 months, P<0.001). Only 16% with central nervous system (CNS) involvement had CNS progressive disease on treatment. No significant progression-free survival (PFS) differences were found between patients with or without CNS disease, regardless of RDI groups. Five patients (5.7%) developed interstitial lung disease (ILD), with 3 (3.4%) having grade 3 events. Two required high-dose steroids and none were rechallenged after ILD. There were no fatalities. CONCLUSION Our study demonstrated that reduced dose intensity and density had no significant impact on rwPFS or treatment-related toxicities. Furthermore, only 5.7% of patients developed ILD. T-Dxd provided good control of CNS disease, with 82% of patients achieving CNS disease control.
Humans ; Female ; Breast Neoplasms/mortality* ; Middle Aged ; Trastuzumab/adverse effects* ; Aged ; Adult ; Singapore/epidemiology* ; Antineoplastic Agents, Immunological/adverse effects* ; Camptothecin/adverse effects* ; Immunoconjugates/adverse effects* ; Retrospective Studies ; Progression-Free Survival ; Receptor, ErbB-2/metabolism* ; Neoplasm Metastasis ; Dose-Response Relationship, Drug ; Treatment Outcome ; Registries

A deep learning-based method for recognizing the minutiae in fingerprint,as well as a Python programming-based evaluation system for quantifying the evidence value of fingerprint was proposed.Firstly,latent fingerprints,which were developed using a series of fluorescent nanomaterials synthesized by chemical methods,were used as unknown fingerprint(UKFP),while ink impressed fingerprints were used as known fingerprint(KFP).Then,the bifurcations and terminations in minutiae were recognized using the improved YOLOv8 deep learning model.After that,the similarity index(Sim.)of UKFP vs KFP were calculated by analyzing the angle similarity factor(α)and the curve similarity factor(β)between UKFP and KFP,meanwhile,the sensitivity index(Sen.)were calculated by analyzing the fineness factor(γ)between UKFP and KFP.The evidence value(EV)of fingerprint was thus obtained by the combination of Sim.and Sen..The calculation formulas for above evaluation factors(i.e.α,β and γ),evaluation indexes(i.e.Sim.and Sen.),and EV were also put forward.Finally,the evaluation system for quantifying the evidence value of fingerprint was established,the feasibility and reliability of this system were verified,and the external factors that impacted on Sim.,Sen.,and EV were investigated in detail.The Python-based evaluation system for quantifying the evidence value of fingerprint could achieve the goals objectively,comprehensively,accurately and efficiently,exhibiting easy operability,high efficiency,responsiveness and reliability.This research was expected to provide beneficial references for quantitatively evaluating and thoroughly developing the evidence value.

The anti-counterfeiting application of three-color fluorescent carbon dots(CDs)in high-quality inkjet printing was studied.Blue,green and red fluorescent CDs were synthesized by solvothermal method using three kinds of isomers of phenylenediamine as precursor,and ethanol-glycerol mixture as solvent.The morphology,composition,structure,and optical properties were characterized.Blue,green and red fluorescent inks were then prepared by diluting CDs with water.The dilution ratio,excitation light source and filtering method were also optimized.The optimal dilution ratio of blue,green and red fluorescent ink was 5,5 and 20,respectively.Under 365,415 and 450 nm light excitation,bright blue,green and red fluorescence from above inks could be observed by using a blue,green and red filter,respectively.These fluorescent inks were finally used for high-quality inkjet printing through monochrome printing mode and polychrome printing mode.In addition,the sensitivity and contrast of printing were quantitatively investigated.The series of three-color fluorescent inks possessed great prospects in ordinary and invisible fluorescent anti-counterfeiting application.

Nonobstructive azoospermia (NOA), one of the most severe types of male infertility, etiology often remains unclear in most cases. Therefore, this study aimed to detect four biallelic detrimental variants (0.5%) in the minichromosome maintenance domain containing 2 ( MCMDC2 ) genes in 768 NOA patients by whole-exome sequencing (WES). Hematoxylin and eosin (H&E) demonstrated that MCMDC2 deleterious variants caused meiotic arrest in three patients (c.1360G>T, c.1956G>T, and c.685C>T) and hypospermatogenesis in one patient (c.94G>T), as further confirmed through immunofluorescence (IF) staining. The single-cell RNA sequencing data indicated that MCMDC2 was substantially expressed during spermatogenesis. The variants were confirmed as deleterious and responsible for patient infertility through bioinformatics and in vitro experimental analyses. The results revealed four MCMDC2 variants related to NOA, which contributes to the current perception of the function of MCMDC2 in male fertility and presents new perspectives on the genetic etiology of NOA.
Humans ; Male ; Azoospermia/genetics* ; Meiosis/genetics* ; Spermatogenesis/genetics* ; Adult ; Exome Sequencing ; Microtubule-Associated Proteins/genetics* ; Alleles ; Infertility, Male/genetics*

Objective To study the pharmacokinetic(PK)characteristics,bioequivalence and safety of two kinds of vildagliptin tablets in Chinese healthy subjects in postprandial state.Methods A single-center,open,balanced,randomized,single-dose,two-period,two-sequence,crossover design was adopted.Each period,subjects orally took 50 mg of the test formulation or reference formulation after a high-fat meal.Blood samples were collected at preset time points and the plasma concentration of vildagliptin was measured by liquid chromatography/mass spectrometry(LC-MS/MS).The PK parameters were calculated using Phoenix WinNonlin 8.2 software;and the bioequivalence of the two formulations was evaluated.Demographic and baseline characteristics,as well as safety analysis of the subjects,were performed using SAS 9.4 software.Results Out of 24 subjects,one subject withdrew from the trial before administration in the first period,and another withdrew before administration in the second period.Under postprandial conditions,the main pharmacokinetic parameters of vildagliptin tablets for the test and reference formulations were Cmax were(230±73.9)and(203±44.0)ng·mL-1,AUC0-t were(1 065.93±215.46)and(1 029.30±185.78)ng·h·mL-1,AUC0-∞ were(1 078.74±217.93)and(1 041.59±190.66)ng·h·mL-1.The 90％confidence intervals for the geometric mean ratios of Cmax,AUC0-t and AUC0-∞ were within the requirements of the equivalent range of bioequivalence(80.00％-125.00％).During the trial,five subjects experienced mild adverse events,with no serious adverse events occurring.Conclusion Two kinds of vildagliptin tablets have bioequivalence in postprandial state,and have good safety and tolerability in healthy subjects.

Objective To study the pharmacokinetic(PK)characteristics,bioequivalence and safety of two kinds of vildagliptin tablets in Chinese healthy subjects in postprandial state.Methods A single-center,open,balanced,randomized,single-dose,two-period,two-sequence,crossover design was adopted.Each period,subjects orally took 50 mg of the test formulation or reference formulation after a high-fat meal.Blood samples were collected at preset time points and the plasma concentration of vildagliptin was measured by liquid chromatography/mass spectrometry(LC-MS/MS).The PK parameters were calculated using Phoenix WinNonlin 8.2 software;and the bioequivalence of the two formulations was evaluated.Demographic and baseline characteristics,as well as safety analysis of the subjects,were performed using SAS 9.4 software.Results Out of 24 subjects,one subject withdrew from the trial before administration in the first period,and another withdrew before administration in the second period.Under postprandial conditions,the main pharmacokinetic parameters of vildagliptin tablets for the test and reference formulations were Cmax were(230±73.9)and(203±44.0)ng·mL-1,AUC0-t were(1 065.93±215.46)and(1 029.30±185.78)ng·h·mL-1,AUC0-∞ were(1 078.74±217.93)and(1 041.59±190.66)ng·h·mL-1.The 90％confidence intervals for the geometric mean ratios of Cmax,AUC0-t and AUC0-∞ were within the requirements of the equivalent range of bioequivalence(80.00％-125.00％).During the trial,five subjects experienced mild adverse events,with no serious adverse events occurring.Conclusion Two kinds of vildagliptin tablets have bioequivalence in postprandial state,and have good safety and tolerability in healthy subjects.