2型糖尿病患者血清SUA和CysC水平与糖尿病视网膜病变的关系

目的：探讨血清尿酸(SUA)、胱抑素C(CysC)水平与糖尿病视网膜病变(DR)的关系。

方法：前瞻性研究。选取2019-05/2021-05本院收治无DR的2型糖尿病(T2DM)患者53例和DR患者83例，DR患者中包括非增殖型糖尿病视网膜病变(NPDR)47例、增殖型糖尿病视网膜病变(PDR)36例。另选取同期体检中心体检健康者48人作为对照组。比较受试者血清学指标，尿酸氧化酶法检测SUA水平，免疫比浊法检测血清CysC含量，Spearman相关性分析血清SUA、CysC与其他血清学指标的相关性，多因素线性逐步回归法分析血清SUA、CysC的影响因素，使用受试者工作特征曲线(ROC)分析血清SUA、CysC对DR预测效能。

结果：T2DM组、NPDR组和PDR组的体质量指数(BMI)、收缩压(SBP)均明显高于对照组(均P<0.05)，PDR组的SBP均明显高于T2DM组和NPDR组(均P<0.05)，NPDR组和PDR组糖尿病病程均明显高于T2DM组(均P<0.05)，PDR组糖尿病病程明显高于NPDR组(P<0.05)。对照组、T2DM组、NPDR组、PDR组纳入对象中空腹血糖(FPG)、糖化血红蛋白(HbA1c)、SUA、CysC水平呈逐渐明显升高趋势(均P<0.001)，PDR组的低密度脂蛋白胆固醇(LDL-C)、甘油三酯(TG)水平明显高于对照组(均P<0.05)，而高密度脂蛋白胆固醇(HDL-C)水平明显低于对照组(P<0.05)。血清SUA水平与FPG、HbA1c、TC、TG水平呈正相关(r_s=0.564、0.631、0.513、0.408，P<0.001)，与HDL-C、LDL-C无相关性(r_s=-0.061、0.035，P>0.05)； 血清 CysC水平与FPG、HbA1c、TC、TG水平呈正相关(r_s=0.524、0.692、0.395、0.435，P<0.001)，与HDL-C、LDL-C无相关性(r_s=-0.012、0.049，P>0.05)，FPG、HbA1c、TC、TG是血清SUA、CysC水平影响因素(P<0.001)。SUA、CysC联合检测时曲线下面积(AUC)(0.892，95%CI：0.840～0.944，敏感性71.1%，特异性94.3%)显著高于其单独检测AUC\〖SUA(0.807，95%CI：0.735～0.879，敏感性69.9%，特异性75.5%)、CysC(0.763，95%CI：0.684～0.841，敏感性69.9%，特异性75.5%)\〗(均P<0.05)。

结论：随着DR病情严重程度加重而血清SUA、CysC水平逐渐升高。血清SUA、CysC联合检测可提高DR诊断预测效能。     

Cyanidin-3-glucoside protects against high glucose-induced injury in human nucleus pulposus cells by regulating the Nrf2/HO-1 signaling

Cyanidin-3-glucoside (C3G) is a well-known natural anthocyanin with antioxidant and anti-inflammatory properties. In this study, we explored the role and action mechanism of C3G in high glucose (HG)-induced damage of human nucleus pulposus cells (HNPCs). Cell viability was assessed by CCK-8 assay. TUNEL assay was performed for detecting apoptotic rate. Western blot was performed to determine the expression levels of cl-caspase-3, caspase-3, Bax, Bim, collagen II, aggrecan, MMP-3, MMP-13, and ADAMTS5. Reactive oxygen species (ROS) generation was analyzed using DCFH-DA staining. The Nrf2 was knocked down or overexpressed in HNPCs through transfection with si-Nrf2 or pcDNA3.0-Nrf2. C3G treatment (12.5, 25, and 50 μM) improved cell viability of HNPCs under HG condition. HG-induced cell apoptosis of HNPCs was attenuated by C3G with decreased apoptotic rate and relative levels of cl-caspase-3/caspase-3, Bax, and Bim. C3G treatment caused significant increase in expression levels of collagen II and aggrecan and decrease in the relative levels of MMP-3, MMP-13, and ADAMTS5. After treatment with C3G, ROS generation in HNPCs was markedly reduced. Treatment with N-acetylcysteine (NAC) reversed HG-induced cell apoptosis and extracellular matrix (ECM) degradation. C3G treatment induced the expression of Nrf2 and HO-1 in HG-induced HNPCs. Moreover, knockdown of Nrf2 reversed the inhibitory effect of C3G on ROS production. Summarily, C3G exerted a protective effect on ROS-mediated cellular damage in HNPCs under HG condition, which was attributed to the induction of the Nrf2/HO-1 signaling pathway.     

《针灸大成》关于气海穴临床应用的文献研究

目的:通过检索《针灸大成》中与气海穴治疗作用相关的文献条文,总结气海穴在治疗各系统疾病中运用频次较高的疾病及其配穴规律,为临床针灸对气海穴的使用提供理论支持。方法:以《中华医典》(第五版)中《针灸大成》作为文献检索来源,将气海穴及气海穴的别称“脖胦”“下肓”“丹田”“肓之原”“肓原”“下言”和“气泽”为检索词,用计算机检索工具及人工检索相结合的方法检索符合要求的文献条文,通过建立本研究的数据库,频次分析、条形统计图比较分析等方法,总结出气海穴在治疗各系统疾病中的运用频次及其配穴规律。结果:在《针灸大成》所涉及的条文中,气海穴尤善治疗内科疾病,在治疗内科疾病中排名前3位的是脾胃系病症、气血津液疾病、肾系病症和妇科疾病,气海穴配穴习惯为上下配穴法,同名经配穴法,以及前后配穴法,其中主要为前后配穴法和同名经配穴法。结论:气海穴《针灸大成》中单穴应用占比最高,而在气海穴众多配穴中,运用了本经配穴法、上下配穴法、前后配穴法,配穴归经主要来自任脉和足太阳膀胱经。同名经配穴法,同气相求,可增加疗效;与气海穴配伍较多的足太阳膀胱经以背腧穴为主,此为前后配穴法,亦称腹背阴阳配穴法,腹部为阴,腰背为阳,前后配穴法可起到“从阳引阴”亦可“从阴引阳”的作用,以达到调节阴阳,调和脏法,调畅经络的目的。     

New era for myelofibrosis treatment with novel agents beyond Janus kinase-inhibitor monotherapy: Focus on clinical development of BCL-XL/BCL-2 inhibition with navitoclax

Myelofibrosis is a heterogeneous myeloproliferative neoplasm characterized by chronic inflammation, progressive bone marrow failure, and hepatosplenic extramedullary hematopoiesis. Treatments like Janus kinase inhibitor monotherapy (e.g., ruxolitinib) provide significant spleen and symptom relief but demonstrate limited ability to lead to a durable disease modification. There is an urgent unmet medical need for treatments with a novel mechanism of action that can modify the underlying pathophysiology and affect the disease course of myelofibrosis. This review highlights the role of B-cell lymphoma (BCL) protein BCL-extra large (BCL-X_L) in disease pathogenesis and the potential role that navitoclax, a BCL-extra large/BCL-2 inhibitor, may have in myelofibrosis treatment.     

A multidisciplinary approach for prenatal diagnosis of FRASER SYNDROME-report of a novel variant in FRAS1

ObjectiveWith this case report, we would like to highlight the importance of a multidisciplinary approach and atypical findings of congenital high airway obstruction sequence (CHAOS), anhydramnios, and renal dysgenesis in the prenatal diagnosis of Fraser syndrome (FS).Case reportA 25-year-old primigravida at 19 weeks of routine anomaly scan revealed abnormal sonographic findings such as fetal bilateral dysplastic small kidneys and gross oligohydramnios. The further detailed evaluation revealed that both fetal lungs were hyperechogenic with prominent (dilated) trachea and bronchi suggestive of CHAOS. Based on these findings, a diagnosis of FS was suspected. The couple was counseled and the pregnancy was terminated. The postmortem evaluation and novel homozygous variant in the FRAS1 gene confirmed the diagnosis of FS.ConclusionThe diagnosis and counseling of the patient were supported by a well-coordinated, multidisciplinary approach involving an obstetrician, a fetal medicine specialist, a medical geneticist, and a fetal pathologist.     

Dual-target inhibitors of bromodomain-containing protein 4 (BRD4) in cancer therapy: Current situation and future directions

Bromodomain-containing protein 4 (BRD4) is emerging as a therapeutic target that acts synergistically with other targets of small-molecule drugs in cancer. Therefore, the discovery of potential new dual-target inhibitors of BRD4 may be a promising strategy for cancer therapy. In this review, we highlight a series of strategies to design therapeutic dual-target inhibitors of BRD4 that focus on the synergistic functions of this protein. Drug combinations that exploit synthetic lethality, protein–protein interactions, functional complementarity, and blocking of resistance mechanisms could ultimately overcome the barriers inherent to the development of BRD4 inhibitors as future cancer drugs.     

日本汉方药企业近十年申请专利的分析及思考——以津村制药和Kracie为例＊

目的 对日本医疗用汉方医药品和一般用汉方医药品市场占有率最大的企业日本津村制药公司和Kracie制药公司2008-2020年间申请的专利内容进行综述，为国内中药经典名方和保健食品研发、知识产权保护提供参考。方法 通过日本专利局的官方检索渠道J-PlatPat平台，检索日本津村制药公司和Kracie制药公司在2008年至2020年间申请的专利，并进行专利布局和技术内容分析。结果 共收集43项日本津村制药公司特许和实用新案专利，其围绕汉方制剂产品全过程质量控制构建了坚实的专利技术体系；共收集52项Kracie制药公司特许和实用新案专利，其致力于功能性制剂和组合物的开发，重点在生活改善、老龄化和癌症等领域进行专利布局，还创建了多种产品功效和功能的客观评价方法。结论 津村制药近十年专利布局提示在中药现代化制造和走向国际的过程中，应把提高品质作为主攻方向，树立持续质量改进理念，完善产品有效性证据链。Kracie制药公司践行的以人为中心的汉方药设计理念，以及精准满足消费者健康需求的研发模式值得借鉴。