BACKGROUND:Stapokibart is a novel anti-interleukin-4 receptor α (IL-4Rα) monoclonal antibody approved for the treatment of adults with moderate-to-severe atopic dermatitis (AD). OBJECTIVES:To assess the safety, efficacy, pharmacokinetics, pharmacodynamics and immunogenicity of stapokibart in children with moderate-to-severe AD. METHODS:This was a multicentre open-label single-arm phase Ib/IIa trial (NCT06162507) involving 8 weeks of treatment and 8 weeks of follow-up. Children aged 6-11 years received subcutaneous stapokibart based on a bodyweight-tiered regimen (30-60 kg: 300 mg every 3 weeks for a total of three doses, including a 600-mg loading dose; 15-30 kg: 150 mg every 2 weeks for a total of four doses, including a 300-mg loading dose). RESULTS:Twenty-five patients (13 weighing 30-60 kg; 12 weighing 15-30 kg) received stapokibart; 68% reported mild or moderate adverse events. At week 8, 54% (n = 7/13) of those weighing 30-60 kg and 75% (n = 9/12) of those weighing 15-30 kg achieved a ≥ 75% improvement from baseline in Eczema Area and Severity Index. Stapokibart concentrations increased rapidly following the first dose, climbed further with repeated dosing and gradually declined after treatment discontinuation. Stapokibart reduced inflammatory biomarkers in both groups. No treatment-related antidrug antibodies were detected. No new safety signals emerged. CONCLUSIONS:Stapokibart shows potential in improving disease outcomes and appears to be well tolerated in children aged 6-11 years with moderate-to-severe AD. Larger controlled studies are needed to confirm long-term benefits.
To explore the efficacy and safety of remimazolam besylate in short-term sedation in the ICU in comparison with propofol. A multicenter, randomized, single-blind, non-inferiority trial was conducted in mechanically ventilated patients, who needed light sedation, defined as Richmond Agitation–Sedation Scale (RASS) scores between −2 and + 1. The primary outcome was successful sedation, which was defined as no rescue sedative administered during the study drug infusion period while maintaining RASS scores between –2 and + 1 for at least 70
Background and Objective: Coronary endothelial dysfunction is considered one of the key pathological components in acute myocardial infarction (AMI). This study aimed to explore the expression patterns and potential significance of the differentially expressed genes SULF1 and EPB41L3 in AMI by integrating bioinformatics analysis and clinical validation. Methods: Differentially expressed genes (DEGs) were screened from two public microarray datasets (GSE66360 and GSE132651). Their functional profiles were summarized via Gene Ontology and pathway analysis. In parallel, whole-blood samples from 29 patients with coronary artery disease were collected, and gene expression was measured using quantitative real-time PCR (qPCR). Multivariate logistic regression was adjusted, and bootstrap resampling was applied to assess robustness. Exploratory single-cell expression analysis and drug-gene interaction prediction were also performed. Results: Bioinformatics analysis identified SULF1 and EPB41L3 as consistently upregulated in AMI. In clinical samples, both genes showed significantly higher expression in AMI patients compared with non-obstructive coronary artery disease controls (P=0.036 and 0.021), and this association remained significant after multivariate adjustment (P=0.039 and 0.034). Single-cell data indicated expression in endothelial cells and fibroblasts. Drug prediction suggested metoprolol and paclitaxel as potential modulators of SULF1. Conclusion: This study, through integrated analysis, first validated the upregulated expression of candidate biomarkers SULF1 and EPB41L3 in the peripheral blood of AMI patients within a clinical cohort. Combined with their baseline expression profiles in cell types associated with vascular inflammation such as endothelial cells, these findings suggest that these two genes may be involved in the pathological process of AMI. This research provides new candidate targets and clues for exploring the molecular mechanisms of AMI.
BackgroundSSGJ-608 is an anti-interleukin-17A monoclonal antibody with high specificity and high affinity and has shown promising efficacy in treatment of moderate-to-severe psoriasis in preliminary trials.ObjectiveThis multicenter, randomized, open-label, phase 3 trial aimed to further evaluate SSGJ-608 at different dosing intervals (80mg every two weeks and 160mg every four weeks) in patients with moderate-to-severe plaque psoriasis.MethodsA total of 770 patients with moderate to severe plaque psoriasis were randomly assigned (1:1) to receive subcutaneous injections of 80mg of SSGJ-608 every two weeks (Q2W) after a starting dose of 160mg at week 0(608A group), or 160mg of SSGJ-608 every four weeks (Q4W) (608 B group) for 12 weeks. Efficacy was assessed by PASI75 and sPGA 0 or 1 response rates at week 12 as co-primary endpoints, and proportion of patients who achieved PASI90, PASI100 or sPGA score of 0 at week 12 as secondary endpoints. The safety profile was also evaluated.ResultsAt week12, the proportions of patients achieving PASI75 (92.7% vs. 95.1%) and sPGA 0/1 (80.3% vs. 79.0%) were comparable between the two SSGJ-608 dose regimens. The PASI90, PASI100 and sPGA 0 response rates were 81.0% vs.82.3%, 49.4% vs. 47.5%, and 49.4% vs.47.3% in the 608A group and the 608B group, respectively. In the subgroup of patients previously treated with anti-IL-17 therapy, SSGJ-608 also achieved high clinical response rates at week12. The most common TEAEs were hypertriglyceridemia, upper respiratory tract infection, hyperuricemia, increased alanine aminotransferase and hypercholesterolemia. Both treatment groups demonstrated a favorable safety profile and no new safety signals were identified.ConclusionsSSGJ-608 was highly effective for treating patients with moderate-to-severe plaque psoriasis at 80mg Q2W and 160mg Q4W in a larger population, especially in patients previously treated with anti-IL-17 therapy, and exhibited a favorable tolerability profile in Chinese patients with moderate-to-severe plaque psoriasis.Clinical trial registrationhttps://clinicaltrials.gov/, identifier NCT06299982.
Gastric dyskinesia, as a functional gastrointestinal disorder characterized by delayed gastric emptying, involves neuro-muscular dysfunction and intestinal flora imbalance. Traditional assessment methods have limitations such as complex operation and low temporal resolution. In recent years, electrochemical sensors have shown significant application value in the field of medical testing due to their high sensitivity, rapid response, miniaturization, and good biocompatibility. This technology converts biological recognition events into quantifiable electrical signals, enabling real-time, label-free detection of key metabolites such as short-chain fatty acids, lipopolysaccharides, and neurotransmitters in feces, breath, or body fluids. It provides a new technical path for the precise classification of gastric dyskinesia, dynamic monitoring of therapeutic effects, and mechanism analysis. The study adopted a prospective cohort design, including patients diagnosed with gastric dyskinesia who received intervention with nano-sustained motility-promoting drugs. 16S rRNA sequencing and metabolomics analysis were used to evaluate changes in intestinal flora structure and metabolites before and after treatment. Although data were not directly obtained using electrochemical sensing equipment, the identified key biomarkers (such as acetic acid, propionic acid, butyric acid, indole, 5-hydroxytryptamine, etc.) are all current key targets for the development of electrochemical sensors. Existing studies have shown that electrochemical platforms based on carbon nanomaterials, molecularly imprinted polymers, or field-effect transistors can achieve nanomolar-level detection of these metabolites, demonstrating good clinical translation potential. The results showed that after intervention, patients' gastric emptying function improved, accompanied by an increase in specific beneficial bacteria abundance and a decrease in pro-inflammatory metabolite levels, suggesting that the drug has a dual effect of regulating the interaction between the microbiota and the host. These metabolic changes provide clear molecular evidence for the application of electrochemical sensors in the management of gastric dyskinesia.
