Zaozhuang Municipal Hospital

Abstract Aims To characterize the pharmacogenomic landscape in a Chinese Type 2 Diabetes Mellitus (T2DM) cohort and develop a systematic framework to translate raw genotype data into predicted clinical phenotypes. Methods In this retrospective study of 908 Chinese patients, we used a novel 'Interpretation Rulebook' to derive eight predicted phenotypes from seven SNPs. These classifications are genotype-based, not measured clinical outcomes. A weighted polygenic risk score (PRS) for T2DM was constructed and evaluated for its ability to discriminate the genotype-derived risk classification. Results Allele frequencies were consistent with East Asian populations. Predefined genetic variants were the primary drivers of their corresponding phenotype classifications, for instance, IRS1 rs1801278 for insulin resistance risk (Adjusted OR = 6450.06) and SLCO1B1 rs4149056 for predicted repaglinide efficacy (OR = 0.00009). The T2DM PRS demonstrated excellent discriminatory power for the genotype-derived risk classification (AUC = 0.990). Conclusions This study establishes a transparent and validated framework for standardizing real-world pharmacogenomic data. The high-performance PRS confirms its internal logic, providing a robust blueprint for clinical decision support and implementing pre-emptive pharmacogenomic testing. While acknowledging the need for prospective validation against measured outcomes, this work addresses the translational gap in interpreting heterogeneous genetic data.

Rheumatoid arthritis (RA) is a chronic, immune-mediated disease with symmetric polyarticular pain and swelling. It includes seropositive RA, marked by specific antibodies, and seronegative RA, without these antibodies. The relationship between immune cells and both types of RA has not been fully elucidated. Therefore, we conducted a two-sample Mendelian randomization analysis with bidirection to evaluate the causal relationship between immune cells and both seropositive and seronegative RA. We utilized data from various genome-wide association studies and employed multiple analytical methods, including inverse-variance weighted and Wald ratio, as the primary method. Additionally, we employed supplementary approaches such as MR-Egger regression, weighted median, and weighted mode. Various sensitivity analyses were used to ensure the robustness of our results. Furthermore, we utilized the false discovery rate method to mitigate type 1 error. We identified 3 immune cell types linked to higher seropositive RA risk, and 16 immune cell types might be influenced by seronegative RA (4 increased and 12 decreased). Notably, HLA-DR+ monocytes were strongly associated with seropositive RA, while changes in immune cell composition in seronegative RA suggest potential biomarkers for its diagnosis. These findings offer valuable insights into RA pathogenesis and highlight the potential for novel diagnostic and therapeutic strategies, particularly for seronegative RA, which lacks reliable biomarkers. Further research is needed to explore the underlying mechanisms and their clinical applications.

ObjectiveTo assess the clinical efficacy of acupressure application in treating postherpetic neuralgia (PHN) of the qi (vital energy) stagnation and blood stasis type, as well as its impact on blood inflammatory factors, T-cell subpopulations, and neurotransmitter levels.MethodsA total of 134 patients diagnosed with PHN characterized by qi stagnation and blood stasis were randomly assigned to either the treatment group (67 patients, including 10 dropouts) or the control group (67 patients, including 7 dropouts). In addition to standard health education, the treatment group received treatment with anti-swelling and analgesic patches in combination with Chinese medicine fine powder acupoint patches. The control group, on the other hand, received placebo anti-swelling and analgesic patches along with placebo Chinese medicine fine powder acupoint patches. Both groups underwent treatment at specific acupoints including bilateral Sanyinjiao, Shenque, and Ashi points. The Sanyinjiao acupoint was stimulated for 30 min per session, once every 7 days. The Shenque and Ashi acupoints were stimulated for 6–8 h daily for a single session. Patients in both groups were assessed before and after treatment using the Visual Analog Scale (VAS) score, Traditional Chinese Medicine (TCM) syndrome score, Pittsburgh Sleep Quality Index (PSQI) score, 36-item Short Form Health Survey (SF-36) score, inflammatory factors including monocyte chemotactic protein-1 (MCP-1), interleukin 6 (IL-6), tumor necrosis factor alpha (TNF-α), T-cell subpopulations cluster of differentiation 3 (CD3+), cluster of differentiation 4 (CD4+), cluster of Differentiation d (CD8+), as well as neurotransmitters 5-hydroxytryptamine (5-HT), substance P (SP), and β-endorphin (β-EP). Changes in content were observed, and any adverse reactions were monitored. Clinical efficacy was evaluated after a 4-week treatment period.ResultsAfter 4 weeks of treatment, the VAS score, TCM syndrome score, PSQI score, levels of MCP-1, IL-6, TNF-α, CD8+, 5-HT, and SP in both groups significantly decreased compared to pre-treatment levels (P < 0.05). Moreover, these parameters were lower in the treatment group than that in the control group (P < 0.05). Conversely, the SF-36 scores, CD3+, CD4+, and β-EP levels were significantly higher in post-treatment analyses compared to that at the baseline (P < 0.05). In addition, these values were higher in the treatment group than that in the control group (P < 0.05). The total effective rate in the treatment group was 84.21%, significantly surpassing the control group's rate of 61.67% (P < 0.05).ConclusionAcupuncture point paste therapy for PHN of the qi stagnation and blood stasis type has been shown to decrease levels of MCP-1, IL-6, TNF-α, CD8+, 5-HT, and SP in the blood. Simultaneously, it increases levels of CD3+, CD4+, and β-EP. This treatment leads to amelioration of pain symptoms and TCM symptoms and enhancement of sleep quality and overall quality of life. The therapeutic outcomes are both safe and dependable.Clinical Trial RegistrationCONSORT ChiCTR2200056614.

BackgroundXeligekimab is a novel immunoglobulin G4 (IgG4) monoclonal antibody targeting interleukin-17A (IL-17A). In a phase III trial in patients with plaque psoriasis, xeligekimab showed efficacy and safety consistent with other IL-17A inhibitors, supporting its potential application in the treatment of spondyloarthritis.ObjectiveThis phase III trial aimed to investigate the efficacy and safety of xeligekimab in patients with radiographic axial spondyloarthritis (r-axSpA).MethodsThis was a phase III study conducted at multiple centers in China. Eligible patients were randomly assigned (1:1:1) to receive xeligekimab 100 mg, xeligekimab 200 mg, or placebo. Randomization was stratified by medication history (biologic-experienced vs. biologic-naïve) and weight (≥ 70 kg vs. < 70 kg). The primary endpoint was the proportion of patients achieving an Assessment of SpondyloArthritis International Society 20 (ASAS20) response at week 16. A key secondary endpoint was the ASAS40 response rate at the same time point.ResultsA total of 465 patients were recruited. A significantly higher proportion of patients receiving xeligekimab 200 mg (n = 114 (74.0%); p < 0.001, 95% confidence interval (CI) 28.5–48.4) and xeligekimab 100 mg (n = 102 (65.8%); p < 0.001, 95% CI 19.4–41.0) achieved an ASAS20 response compared to the placebo group (n = 56 (35.9%)) at week 16. Similarly, a significantly higher ASAS40 response rate was observed in the xeligekimab 100 mg group (n = 62 (40.0%); p < 0.001) and the xeligekimab 200 mg group (n = 64 (41.6%); p < 0.001) compared to placebo. Adverse events were similar across all groups, with serious adverse events occurring in 1.6% of the treatment group during the core treatment period. No unexpected safety signals were reported through week 48.ConclusionXeligekimab demonstrated significant efficacy in improving the signs and symptoms of active r-axSpA in Chinese patients at week 16, with sustained effects observed through week 48 and no new safety signals identified.Trial RegistrationClinicalTrials.gov identifier: NCT05881785 (Date: 21 May 2023).Supplementary InformationThe online version contains supplementary material available at 10.1007/s40259-025-00750-0.

This randomized, double-blind, adaptive phase 2/3 trial aimed to evaluate the efficacy and safety of ivarmacitinib, a novel selective JAK1 inhibitor, in patients with active ankylosing spondylitis (AS). In phase 2, patients were randomized (1:1:1:1) to receive ivarmacitinib at a dose of 2, 4, or 8 mg or placebo once daily for 12 weeks. Based on interim analysis, ivarmacitinib 4 mg was selected as the recommended dose. In phase 3, patients were randomized (1:1) to receive ivarmacitinib 4 mg or placebo for 12 weeks; from week 12 onward, all patients received ivarmacitinib 4 mg once daily through week 24. The primary end point was the proportion of patients achieving a ≥20% improvement in the Assessment of SpondyloArthritis international Society (ASAS20) response criteria at week 12. During the entire study, 504 patients were randomized (ivarmacitinib 4 mg, n = 187; placebo, n = 186). At week 12, the ASAS20 response rate was significantly higher in the ivarmacitinib 4 mg group compared to the placebo group (48.7% vs 29.0%; one-sided P = 0.0001). The ASAS40 response rate (32.1% vs 18.3%) and all other secondary end points also favored ivarmacitinib 4 mg. Efficacy was sustained through 24 weeks. During the placebo-controlled period, treatment-emergent adverse events occurred in 79.7% of the ivarmacitinib group and 65.6% of the placebo group. Ivarmacitinib 4 mg significantly improved the signs and symptoms of AS at week 12 compared to placebo, with sustained efficacy through 24 weeks and a tolerable safety profile. These findings support ivarmacitinib 4 mg as a new treatment option for active AS.

NPS-2143, as a CaSR allosteric antagonist, performs an important role in diverse cancers. However, the function and mechanism of NPS-2143 in human retinoblastoma have not been reported. Cell viability was evaluated by using cell counting kit-8, flow cytometry was used for apoptosis detection and western blotting was carried out to detect the expression of target genes. Small interference RNA (siRNA) was used to reduce CaSR expression. Bortezomib was used to suppress the NF-κB pathway. NPS-2143 (16.5 µM) suppressed the proliferation of Y-79 cells, and increased the apoptosis of Y-79 cells. NPS-2143 treatment inhibited the protein patterns of p-P65 NF-κB and p-IκBα. Additionally, si-CaSR transfection obviously decreased the proliferation of Y-79 cells, and increased the apoptosis of Y-79 cells. Moreover, the protein patterns of p-P65 NF-κB and p-IκBα were obviously decreased after si-CaSR transfection. Bortezomib treatment increased the apoptosis of Y-79 cells, and CaSR overexpression suppressed the apoptosis of Y-79 cells. The whole data indicated that NPS-2143 inhibited the viability of Y-79 cells, and induced apoptosis by modulating the NF-κB signaling pathways. Therefore, NPS-2143 has potential anti-retinoblastoma effect.