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关键词： B activation   Brazilein   Constitutive NFκ   IKK activation   RIPK1 ubiquitination   TNF  

摘要： Ubiquitination of RIPK1 serves as a critical regulatory switch in determining the outcome of prosurvival NF-κB signaling by linking the TNFR1 signaling complex to upstream IKK activation. Therefore, identifying bioactive compounds that modulate RIPK1 ubiquitination has emerged as a promising strategy to enhance the therapeutic efficacy of TNF, particularly in cancers with constitutively active NF-κB signaling. In our previous phytochemical study, we demonstrated that brazilin, isolated from L., inhibits the catalytic activity of the IKK complex during TNF-mediated NF-κB activation without affecting RIPK1 ubiquitination at high concentrations (~50 μM), raising concerns about off-target effects. In this study, we now report that brazilein, an oxidized derivative of brazilin, acts as a potent inhibitor of RIPK1-dependent NF-κB activation upon TNFR1 engagement. Our findings reveal that brazilein markedly suppresses upstream IKK signaling events, including TNFR1-associated RIPK1 polyubiquitination and its interaction with IKKβ. In contrast, brazilein does not affect NIK/IKKκ-mediated non-canonical NF-κB activation induced by LIGHT, indicating its specificity for the canonical NF-κB pathway. Moreover, brazilein not only sensitizes cells to TNF-induced apoptosis but also induces apoptosis in A20-deficient and oncogenically transformed cells with constitutive NF-κB activity. Taken together, these results suggest a novel mechanism by which brazilein exerts anti-IKK activity through inhibition of RIPK1 ubiquitination, highlighting its potential as a candidate for NF-κB-targeted cancer therapy.

关键词： Co γ射线   微核率   剂量率   剂量-效应曲线   胞质分裂阻断微核法  

摘要： 建立并比较两种剂量率60Co γ射线诱导人淋巴细胞微核的剂量-效应曲线。采用剂量率0.318 9 Gy/min和0.635 0 Gy/min60Co γ射线照射离体血样，吸收剂量分别为0 Gy、0.25 Gy、0.50 Gy、0.75 Gy、1 Gy、2 Gy、3 Gy、4 Gy、5 Gy，胞质分裂阻断微核法进行淋巴细胞培养，分析并计算微核率及微核细胞率，拟合剂量-效应曲线。结果表明，两种剂量率下微核率均随吸收剂量而增加，拟合的剂量-效应曲线均符合二次多项式模型；剂量率0.635 0 Gy/min下微核率随吸收剂量而增加的幅度大于剂量率0.318 9 Gy/min。以上研究结果说明，成功建立两种剂量率下微核剂量-效应曲线，为更准确进行生物剂量估算和辐射生物效应研究提供技术支撑和理论依据。

关键词： 3D co-cultures   immunomodulation   immunotherapy   cytotoxicity   adoptive T cell therapy   breast cancer   cytotoxic T lymphocytes  

摘要： T cell-based therapies, involving ex vivo expansion of patients' T lymphocytes, hold significant promise for chemotherapy resistant cases of breast cancer (BC), although their effectiveness remains challenging. Building on our previous findings that the expression of the antigen presenting molecule, HLA-DR, is crucial on tumor-infiltrating cytotoxic T lymphocytes (CTLs) for a favorable response to neoadjuvant chemotherapy, we further investigated the role of HLA-DR-expressing CTLs in anti-tumor responses and evaluated strategies to amplify these cells. Through in vitro and in vivo experiments, we demonstrated that HLA-DR expression on CTLs is important for effective tumor cell elimination. Notably, blocking HLA-DR or depleting CD4+ T cells impaired CTLs activation, suggesting a critical role for antigen presentation by CTLs to CD4+ T cells through HLA-DR in promoting robust anti-tumor responses. Based on these findings we optimized an ex vivo stimulation protocol that increases the proportion of HLA-DR+CTLs with improved cytotoxicity, prioritizing cell quality over yield. Moreover, we showed that adding anti-PD-1 to the stimulation, further upregulated HLA-DR expression, and intensified CTLs' cytotoxic ability. This aligns with our in silico analysis suggesting a potential regulatory link between PD-1 and HLA-DR via non-coding RNAs. Overall, our findings open new avenues for advancing T cell-based therapies and improve the outcomes of chemotherapy-resistant-BC.

关键词： 会阴侧切   自然分娩   初产妇   生产困难   炎性因子   盆底肌功能异常  

摘要： 探讨会阴侧切、自然分娩方式对初产妇伴生产困难者影响。方法 选取2024年1月-2024年12月我院收治的80例生产困难初产妇作为观察对象,均为单胎妊娠,随机数字法均分为2组。对照组40例采取自然分娩,观察组40例进行常规会阴侧切,比较两组产妇产后盆底肌功能异常情况以及相关炎性因子水平变化。结果 生产后,观察组盆底肌功能异常发生情况、血清炎性因子水平、并发症发生率低于对照组(P<0.05)。结论 采取会阴侧切术能够在一定程度上减少产妇盆底肌功能损伤,还能降低相关炎性因子水平,减少并发症发生。

关键词： pharmacogenomics   drug hypersensitivity   psychiatric medications   HLA   CYP450   personalized medicine  

摘要： Drug hypersensitivity reactions (DHRs) to psychiatric medications represent a significant clinical challenge, often resulting in treatment discontinuation, poor adherence, and compromised patient outcomes. Pharmacogenomics has emerged as a promising field for understanding and mitigating these adverse effects by identifying genetic predispositions that affect drug metabolism, immune responses, and individual susceptibility. This narrative review explores the multifaceted mechanisms underlying DHRs, with a focus on immunological pathways, particularly T cell-mediated responses, drug metabolite formation, and genetic risk factors. Among these, human leukocyte antigen (HLA) alleles and polymorphisms in cytochrome P450 (CYP450) enzymes are critical contributors to hypersensitivity development. We provide a comprehensive analysis of pharmacogenomic associations with commonly prescribed psychiatric drugs, including anticonvulsants (e.g., carbamazepine, lamotrigine), selective serotonin reuptake inhibitors (SSRIs), and novel agents such as vortioxetine, psilocybin, and esketamine. Additionally, we examine antipsychotics, including clozapine and newer agents like aripiprazole, brexpiprazole, and cariprazine, highlighting specific gene-drug interactions and known risk alleles such as HLA-B*15:02, HLA-A*31:01, and variants in CYP2D6 and CYP1A2. These findings underscore the value of pharmacogenomic testing in predicting and preventing serious DHRs, such as Stevens-Johnson Syndrome, toxic epidermal necrolysis, agranulocytosis, and hepatotoxicity. The review also addresses clinical implementation, discussing the role of pre-emptive genetic screening, emerging guidelines from international consortia such as CPIC and DPWG, and real-world challenges, including variability in test accessibility, ethical concerns, and a lack of standardized protocols across regions. Recent advances in next-generation sequencing and multiomic approaches offer new opportunities to improve predictive a

关键词： 嵌合抗原受体T细胞疗法   儿童难治急性B淋巴白血病   近期疗效   远期疗效  

摘要： 评价嵌合抗原受体T细胞(CAR-T)疗法对于儿童难治急性B淋巴白血病(B-ALL)的治疗有效性。方法 选择2023年1月至2024年10月间入院治疗的78例B-ALL患儿,随机数字表均分,观察组实行CAR-T疗法,参照组实行常规药物治疗,对比两组的治疗效果。结果 观察组的近期疗效与远期疗效均高于参照组(P<0.05)。治疗后,观察组的炎性因子水平低于参照组(P<0.05)。观察组的不良反应率低于参照组(P<0.05)。结论 为B-ALL患儿实行CAR-T治疗的效果较佳,可获得较佳的近期与远期疗效,且能下调炎症因子水平,其治疗后的不良反应较少。

关键词： Bruton's tyrosine kinase   Monocyte plasticity   Monocyte HLA-DR   X-linked agammaglobulinemia  

摘要： Bruton's tyrosine kinase (BTK) is expressed by innate immune cells, and it has been suggested that a lack of BTK may affect monocytes, impacting infection susceptibility and inflammatory response in patients with X-linked agammaglobulinemia (XLA). This study aimed to explore the role of monocyte subsets and monocyte human leucocyte antigen DR (mHLA-DR) expression in patients with XLA. Fifty-nine patients diagnosed with XLA and 37 age-matched healthy subjects were enrolled, and their demographic and clinical features were recorded. Three monocyte subsets were identified-classical (CL) (CD14(++)CD16(-)), intermediate (INT) (CD14(++)CD16(+)), and non-classical (NC) (CD14(low)CD16(++))-and their mHLA-DR expressions (mean fluorescence intensity, MFI) were determined by flow cytometry. We evaluated monocyte plasticity as the classical/intermediate monocyte (CMIM) ratio. Patients with XLA comprised 38 children (mean age, 10.46 +/- 4.81 years) and 21 adults (25.09 +/- 6.18 years). Compared to the control group, patients had decreased classical (p = .012) but increased intermediate and non-classical monocytes (p < .001 and p = .048, respectively). They also presented with increased mHLA-DR expression of total monocytes and their subsets compared to the healthy subjects (p < .05). There were 17 patients with bronchiectasis (28.8% of total, three children and 14 adults), and they had decreased mHLA-DR of non-classical monocytes and a low CMIM ratio compared with non-bronchiectasis XLA patients (p < .001). The study findings may indicate that a defect in adaptive immune mechanisms leads to compensatory changes in the innate immune system. Monocyte HLA-DR expression and CMIM ratio can be used as potential biomarkers to predict chronic complications, including bronchiectasis in patients with XLA.

关键词： 腰椎穿刺术   急性淋巴细胞白血病   集束化护理   患儿  

摘要： 腰椎穿刺术对急性淋巴细胞白血病患儿进行诊疗中,分析给予集束化护理的效果。方法 选取广西玉林市红十字会医院34例急性淋巴细胞白血病患儿,其均进行腰椎穿刺术诊疗,护理中参照用常规护理,对比分析集束化护理对腰椎穿刺术患儿的益处。结果 术中配合度、一次穿刺成功率、不同时刻心率和呼吸、疼痛评分,以及护理后医疗恐惧评分,两组各指标差异有意义,(P<0.05)。结论 腰椎穿刺术对急性淋巴细胞白血病患儿进行诊疗中,给予集束化护理效果显著,值得应用。

关键词： 粘连性肠梗阻   开腹肠粘连松解术   腹腔镜肠粘连松解术  

摘要： 研究粘连性肠梗阻(AIO)患者接受腹腔镜与开腹肠粘连松解术疗效。方法 2022年2月-2025年2月就诊30例AIO患者为样本,抽签分组。A组腹腔镜肠粘连松解术,B组开腹肠粘连松解术。结果 A组手术指标、炎症因子、应激因子、并发症指标优于B组,P<0.05。结论 腹腔镜肠粘连松解术治疗AIO,术后炎症反应、应激反应轻微,并发症少,有利于缩短AIO术后住院时间。

关键词： Folate-modified chitosan   Drug repurposing   Ferroptosis   Gene expression   Molecular docking   Targeted nanotherapy   Chemoresistant cancer  

摘要： BackgroundHepatocellular carcinoma (HCC) is a leading cause of cancer mortality, largely due to multidrug resistance (MDR). Pioglitazone (PIO) and simvastatin (STAT), originally used for metabolic disorders, also modulate oncogenic pathways. This study evaluated a nanotechnology-based co-delivery approach to improve their therapeutic efficacy against chemoresistant *** and resultsLipid nanoparticles (LNPs) encapsulating PIO and STAT (PSLNPs) were fabricated and functionalized with chitosan (CPSLNPs) or folate-conjugated chitosan (FCPSLNPs). Physicochemical properties (size, zeta potential, polydispersity) were characterized. Hemolysis and MTT assays assessed safety and cytotoxicity in HepG2 cells. qPCR quantified IL-1 beta, IL-6, BCL2, and BAX expression. Molecular docking examined drug interactions with key proteins involved in proliferation, ferroptosis, inflammation, and MDR. All formulations exhibited nanoscale size and uniform dispersion. Chitosan modification increased zeta potential, and stability studies confirmed consistent physicochemical properties. Hemolysis assays demonstrated biocompatibility. Compared with free drugs, PSLNPs and their functionalized forms significantly enhanced cytotoxicity in HepG2 cells. Gene expression analysis showed downregulation of IL-1 beta, IL-6, and BCL2, with upregulation of BAX, indicating enhanced apoptosis. Docking studies revealed STAT strongly interacted with SDH, GST, HDAC1, and JNK3, while PIO showed higher affinity for COX-2, GPX4, HO-1, and MMP-9, supporting complementary multi-target *** PSLNPs improved the delivery and efficacy of PIO and STAT, overcoming MDR by modulating multiple oncogenic pathways. These results highlight their promise as a multi-targeted nanotherapeutic strategy for HCC treatment.