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关键词： 卵巢癌   初始细胞减灭术   术后并发症   辅助化疗开始延迟  

摘要： 目的探讨血小板-淋巴细胞比值(PLR)、中性粒细胞-淋巴细胞比值(NLR)与卵巢癌(OC)初始细胞减灭术(pCRS)术后并发症及辅助化疗开始延迟的相关性。方法选择2020年2月至2022年6月在我院肿瘤科接受pCRS的160例OC患者作为研究对象。术前24 h内使用全自动血液分析仪检测OC患者血细胞计数,计算PLR和NLR。主要研究终点为术后30天内严重并发症,根据pCRS后30天内有无并发症发生分为术后并发症组和无并发症组。次要研究终点为辅助化疗启动延迟的发生率,pCRS至开始化疗之间的时间间隔>1周归为延迟组,其余为未延迟组。结果术后并发症组年龄、国际妇产科联盟(FIGO)分期IV期患者比例、PLR和NLR均显著高于无并发症组(P<0.05)。多元Logistic回归分析显示,年龄≥65岁、FIGO分期IV期、高PLR和NLR是术后并发症发生的独立危险因素(P<0.05)。年龄+FIGO分期+PLR+NLR联合模型预测术后并发症的AUC为0.880,与仅包括年龄和FIGO分期的模型的AUC值比较差异有统计学意义(P<0.001)。辅助化疗开始延迟组年龄、FIGO分期IV期患者比例、PLR和NLR均显著高于未延迟组,体重指数(BMI)显著低于未延迟组(P<0.05)。Logistic回归结果表明PLR和NLR是辅助化疗开始延迟的独立危险因素(P<0.05)。年龄+FIGO分期+BMI+PLR+NLR联合模型预测化疗延迟的AUC为0.845,与仅包括年龄、BMI和FIGO分期的模型的AUC值比较差异有统计学意义(P<0.001)。结论术前高PLR和NLR与OC患者pCRS后并发症和辅助化疗开始延迟高风险有关。

关键词： atopic dermatitis   chronic pruritus   Cnidium monnieri(L.)Cusson   IL-31   NF-κB   osthole   PPAR  

摘要： Objective This study aims to elucidate the therapeutic potential of osthole for the treatment of atopic dermatitis(AD),focusing on its ability to alleviate chronic pruritus(CP)and the underlying molecular *** In this study,we investigated the anti-inflammatory effects of osthole in both a 2,4-dichloronitrobenzene(DNCB)-induced AD mouse model and tumor necrosis factor-α(TNF-α)and interferon-γ(IFN-γ)stimulated huma immortalized epidermal(HaCaT)*** anti-itch effect of osthole was specifically assessed in the AD mouse *** methods such as hematoxylin and eosin(HE)staining,enzyme-linked immunosorbent assay(ELISA),western blot(WB),quantitative real-time PCR(qRT-PCR),and immunofluorescence *** Osthole improved skin damage and clinical dermatitis scores,reduced scratching bouts,and decreased epidermal thickness AD-like *** also reduced the levels of interleukin(IL)-31 and IL-31 receptor A(IL-31 RA)in both skin tissues and HaCaT ***,Osthole suppressed the protein expression levels of phosphor-p65(p-p65)and phosphor-inhibitor of nuclear factor kappa-Bα(p-IκBα).Meanwhile,it increased the protein expression levels of peroxisome proliferator-activated receptorα(PPARα)and PPARγin HaCaT *** These findings indicated that osthole effectively inhibited CP in AD by activating PPARα,PPARγ,repressing the NF-κB signaling pathway,as well as the expression of IL-31 and IL-31 RA.

关键词： 糖尿病肾脏病   NF-κB信号通路   益气活血方   炎症  

摘要： [目的]观察益气活血方干预糖尿病肾脏病(DKD)大鼠后肿瘤坏死因子-α(TNF-α)/核转录因子-κB(NF-κB)信号通路的表达变化探讨益气活血方对DKD大鼠肾脏的保护作用。[方法]雄性SD大鼠通过腹腔注射链脲菌素(STZ)并联合高糖高脂饲养建立DKD模型,剔除死亡及未成模大鼠,设置模型组、厄贝沙坦组、益气活血方高、中、低剂量组及对照组。各组大鼠按对应药物/纯水连续灌胃干预8周。干预阶段,持续观察记录一般状态、随机血糖(RBG)、体质量、日摄食量、日饮水量及24 h尿微量白蛋白(MAU)含量。干预结束后,检测血清中的尿素氮(BUN)、空腹血糖(FBG)、血肌酐(SCr)、总胆固醇(TC)及三酰甘油(TG)含量,并计算肾脏肥大指数(RHI);采用苏木精-伊红(HE)染色观察肾脏病理变化,免疫组化和蛋白免疫印(Western blot)法检测NF-κB p65、TNF-α及细胞间黏附分子-1(ICAM-1)蛋白在肾组织的表达。[结果]与对照组相比,模型组RBG显著升高(P<0.001)并出现体质量减少、多饮、多食及多尿等典型症状;其次,FBG、TG、TC、SCr、BUN、24 h MAU及RHI明显升高(P<0.01或P<0.001);肾脏病理观察显示,肾小球肥大、肾小囊腔狭窄或固缩坏死,肾小管上皮细胞肿胀,部分呈空泡样变性,管腔显著变窄,并伴有大量炎性细胞浸润肾间质;肾脏组织中NF-κB p65、TNF-α及ICAM-1的蛋白表达均明显上调(P<0.001)。与模型组相比,益气活血方高剂量组显著降低DKD大鼠的RBG、FBG、24 h MAU、BUN及RHI(P<0.05或P<0.01);减轻肾脏病理损伤,并抑制肾脏组织中NF-κB p65、TNF-α及ICAM-1的蛋白表达(P<0.05或P<0.001)。[结论]益气活血方通过抑制TNF-α/NF-κB信号通路的表达,减轻肾脏的炎症反应,有效缓解肾脏病理损伤,发挥显著的肾保护作用。

摘要： OBJECTIVE:The human leukocyte antigen B27 (HLA-B27) allele is strongly associated with spondyloarthritis (SpA). HLA-B27 is included in SpA classification criteria and referral strategies for axial SpA. Investigations of HLA-B27 testing in usual clinical practice are limited. METHODS:We identified all adult patients tested for HLA-B27 from 1/1/2022 to 12/31/2022 in the Mass General Brigham healthcare system. We examined patient demographics, ordering provider specialty, testing indication, concurrent testing with antinuclear antibodies, rheumatoid factor, or anti-cyclic citrullinated peptide autoantibodies, and rheumatology referral. We compared the rate of rheumatology referral between HLA-B27 positive and negative patients. RESULTS:HLA-B27 tests were ordered for 1960 patients (62.4% female, average age 47.4 years). The most common specialties testing HLA-B27 were rheumatology (39.7%) and ophthalmology (21.4%). The most common indications for HLA-B27 testing were peripheral arthritis (33.0%), uveitis (22.0%), and back pain (16.7%). The majority of HLA-B27 tests (69.3%) were ordered concurrently with other autoantibody tests. A total of 10.9% of HLA-B27 tests were positive. Ophthalmology had the highest positive rate (15.4%) while reactive arthritis was the indication with the highest positive test rate (50%). A greater proportion of HLA-B27 positive patients were referred to rheumatology (53% vs 32%, p=0.002). CONCLUSION:HLA-B27 testing was frequently performed by rheumatologists and nonrheumatologists for a broad spectrum of indications. Co-testing HLA-B27 with ANA and rheumatoid arthritis autoantibodies was common. Nearly half of HLA-B27 positive patients were not referred to rheumatology. Further efforts are needed to promote judicious use of HLA-B27 testing and optimize referral pathways to rheumatology.

摘要： Glioblastoma (GBM) is the most common primary brain cancer in adults and carries a median overall survival (OS) of 12-15 months. Effective therapy for recurrent GBM (rGBM) following frontline chemoradiation is a major unmet medical need. Here we report the dose escalation and exploration phases of a phase 1 trial investigating intracerebroventricular delivery of bivalent chimeric antigen receptor (CAR) T cells targeting epidermal growth factor receptor (EGFR) epitope 806 and interleukin-13 receptor alpha 2 (IL-13R alpha 2), or CART-EGFR-IL13R alpha 2 cells, in patients with EGFR-amplified rGBM. Primary endpoints included dose-limiting toxicity, determination of the maximum tolerated dose and recommended dose for expansion, and occurrence of adverse events. Secondary endpoints included objective radiographic response, duration of response, progression-free survival and OS. A total of 18 patients received CART-EGFR-IL13R alpha 2 cells. The maximum tolerated dose was determined to be 2.5 x 107 cells. Of the 18 patients, 10 (56%) experienced grade 3 neurotoxicity;none had grade 4-5 neurotoxicity. Of 13 patients, 8 (62%) with measurable disease at the time of CAR T cell infusion experienced tumor regression, with one confirmed partial response by Modified Response Assessment in Neuro-Oncology criteria (objective radiographic response, 8%;90% confidence interval, 0-32%) and one patient with ongoing durable stable disease lasting over 16 months. Median progression-free survival was 1.9 months (90% confidence interval, 1.1-3.4 months), and median OS was not yet reached at the time of data cut-off (median follow-up time, 8.1 months). These findings indicate that intracerebroventricular delivery of bivalent CART-EGFR-IL13R alpha 2 is feasible and appears safe. CART-EGFR-IL13R alpha 2 cells are bioactive and exhibit a signal of antitumor effect in rGBM. *** registration: NCT05168423.

关键词： 白介素1β   microRNAs   miRanda   荧光素酶报告基因  

摘要： 为确定oar-miR-103和oar-miR-107靶向IL-1β基因的区域及结合能力,验证绵羊oar-miR-103和oar-miR-107对绵羊IL-1β表达的调控作用,用miRanda软件分析oar-miR-103、oar-miR-107靶向IL-1β基因的具体区域和结合能力;将IL-1β基因插入PGL3-promoter荧光素酶报告基因载体XbaⅠ酶切位点,分别将miR-NC、miR-103和miR-107模拟物与荧光素酶质粒共转染,通过双荧光素酶报告试验分析oar-miR-103和oar-miR-107与IL-1β基因区域靶向关系;分离原代绵羊肺泡巨噬细胞,miR-NC、miR-103和miR-107模拟物分别转染原代肺泡巨噬细胞,转染36 h后,通过实时荧光定量PCR(RT-qPCR)检测各组细胞中IL-1β表达水平。结果显示,oar-miR-103和oar-miR-107分别靶向IL-1β基因2个、3个区域;成功构建了荧光素酶报告载体pGL3-promoter-IL-1β;双荧光素酶试验显示,与miR-NC组相比,oar-miR-103和oar-miR-107两组均使pGL3-promoter-IL-1β活性显著下降(P<0.01);与miR-NC组相比,oar-miR-107显著抑制了巨噬细胞IL-1βmRNA转录表达(P<0.05)。说明oar-miR-103和oar-miR-107可通过靶向IL-1β基因区域调节其表达,为解析IL-1β表达机理积累了资料。

关键词： 桥本甲状腺炎   微小核糖核酸-27a   白细胞介素-27   甲状腺球蛋白抗体   甲状腺过氧化物酶抗体  

摘要： 目的 探讨桥本甲状腺炎(HT)患者外周血微小核糖核酸-27a(mi R-27a)、白细胞介素-27(IL-27)水平及临床意义。方法 选取2022年1月至2024年2月收治的120例HT患者作为HT组,另选同期体检的健康者100例作为对照组。收集两组一般资料及甲状腺功能参数,检测并比较两组外周血mi R-27a、IL-27。采用Pearson相关分析mi R-27a、IL-27与甲状腺功能参数的关系,采用受试者工作特征(ROC)曲线分析mi R-27a、IL-27水平对HT的诊断价值。结果 HT组甲状腺疾病家族史占比、促甲状腺激素(TSH)、甲状腺球蛋白抗体(Tg Ab)、甲状腺过氧化物酶抗体(TPOAb)、mi R-27a、IL-27明显高于对照组,游离三碘甲状腺原氨酸(FT3)、游离甲状腺素(FT4)低于对照组(P<0.05,P<0.01)。miR-27a、IL-27水平与HT患者TSH、TgAb、TPOAb呈正相关(P<0.05,P<0.01),与HT患者FT3、FT4无明显相关性(P>0.05)。多因素logistic回归分析显示,有甲状腺疾病家族史、高水平Tg Ab、高水平TPOAb、高水平mi R-27a、高水平IL-27是导致HT发生的危险因素(P<0.05,P<0.01)。ROC曲线分析显示,mi R-27a、IL-27联合检测诊断HT的曲线下面积显著高于单独诊断(P<0.01)。结论 HT患者外周血mi R-27a、IL-27水平升高,且与患者甲状腺功能和抗体有关,mi R-27a、IL-27水平升高增加HT发生风险,对HT的早期诊断具有一定价值。

关键词： 宫颈   人乳头瘤病毒   瑞贝生   干扰素   白细胞介素-6   转化生长因子-β1  

摘要： 目的探讨女性抗毒洁阴复合剂(商品名:瑞贝生)联合干扰素治疗宫颈高危型人乳头瘤病毒(HPV)持续感染的疗效及对患者血清白细胞介素-6(IL-6)、转化生长因子-β1(TGF-β1)水平的影响。方法选取该院2022年3月至2024年3月收治的120例宫颈高危型HPV持续感染患者作为研究对象,按照随机数字表法将其分为2组,对照组(60例)予以干扰素治疗,观察组(60例)在干扰素治疗的基础上联合瑞贝生治疗。比较2组患者的临床疗效、炎症指标水平、病毒载量(HPV16、HPV18)、HPV转阴率以及治疗后不良反应发生情况。结果观察组患者临床总有效率(75.00%)显著高于对照组(45.00%),差异有统计学意义(P<0.05)。治疗后,观察组IL-6、TGF-β1水平,以及病毒载量明显低于对照组(P<0.05)。治疗后观察组高危型HPV转阴率明显高于对照组(P<0.05)。2组的不良反应总发生率比较,差异无统计学意义(P>0.05)。结论瑞贝生联合干扰素治疗宫颈高危型HPV持续感染综合效果较好,在清除高危型HPV,抑制炎症反应和HPV复制等方面优于单独采用干扰素治疗。

关键词： 直肠前切除综合征   补虚健脾通络方   炎症细胞因子   脾气亏虚证  

摘要： 目的:探究补虚健脾通络方对直肠前切除综合征(ARS)患者的疗效以及对炎症细胞因子的影响。方法:选取2020年1月—2023年4月我院收治的脾气亏虚型ARS患者116例,采用随机数字表法分为对照组及观察组,每组各58例。对照组进行基础康复训练,观察组在对照组的基础上同时采用补虚健脾通络方进行治疗。评估并比较治疗前、治疗4周后两组患者的中医证候积分,评估临床疗效,检测两组患者治疗前后炎症细胞因子水平[肿瘤坏死因子α(TNF-α)、白细胞介素6(IL-6)、C反应蛋白(CRP)]及排便相关指标(排便次数及大便失禁频次评分),采用生活质量量表(QLQ-C30)评分评估两组患者治疗前后的生活质量。结果:观察组治疗总有效率为91.38%,高于对照组的75.86%(P<0.05);两组患者治疗后主症、次症及总积分均降低,且观察组各项积分均低于对照组(P<0.05);两组患者治疗后TNF-ɑ、IL-6及CRP水平均降低,且观察组各指标水平更低(P<0.05);两组患者治疗后排便次数、大便失禁频次评分均降低(P<0.05),且观察组低于对照组(P<0.05);两组患者治疗后QLQ-C30评分均升高,且观察组QLQ-C30评分高于对照组(P<0.05)。结论:补虚健脾通络方能够改善ARS患者的临床症状,提高疗效,改善机体炎症水平及排便情况,提高患者生活质量,且安全性较高。

关键词： Tfh   Transplantation   Nano-immunosuppressant   rejection  

摘要： During organ transplantation, immune rejection is a primary cause of graft failure. In the underlying pathophysiology of rejection, T follicular helper (Tfh) cells and interleukin-21 (IL-21) play pivotal roles. Tfh cells exacerbate the humoral immune response by promoting B cell differentiation and antibody production, which leads to damage of the transplanted tissue. IL-21, a key pro-inflammatory cytokine, binds to its receptor (IL-21R) to enhance both the growth and function of Tfh cells, while also further driving B cell activation and differentiation into plasma cells. Building on this knowledge, we have developed a tacrolimus-based nano-inhibitor designed to target Tfh cells. This nano-inhibitor is constructed using a mPEG-PLGA-PLL (PEAL) scaffold, with IL21R monoclonal antibodies conjugated to its surface, and tacrolimus encapsulated within the structure. In vitro experiments demonstrated that this nano-inhibitor effectively targets Tfh cells, inhibiting the differentiation of naive CD4+ T cells into Tfh cells. In co-culture systems of T and B cells, it significantly suppresses the activation of both cell types, leading to a reduction in IgG antibody production. In vivo, the nano-inhibitor selectively targets secondary lymphoid organs, reduces systemic inflammation, minimizes lymphocyte infiltration into the graft, and induces immune tolerance toward the transplanted tissue. In addition, no significant toxicity was observed in vitro or in vivo. As a therapeutic agent that simultaneously modulates both T and B cell responses, we believe it holds significant promise for broader applications in transplantation immunotherapy. Statement of Significance: This study presents a groundbreaking nano-immunosuppressant designed to target both T and B cells, addressing the critical challenge of acute rejection in allogeneic transplantation. By combining tacrolimus nanoparticles with IL-21 receptor antibodies, this immunosuppressant effectively suppresses Tfh cell prolifera