血清FABP4、OPG、CysC、AngⅡ用于诊断妊娠期糖尿病合并妊娠期高血压的临床价值分析

目的:探讨血清脂肪酸结合蛋白4(FABP4)、护骨素(OPG)、胱抑素C(CysC)、血管紧张素(AngⅡ)用于诊断妊娠期糖尿病合并妊娠期高血压疾病患者的临床价值。方法:选择2016年4月～2018年4月于华北理工大学附属医院产科门诊建档并定期规律产检的妊娠期糖尿病300例,其中104例并发妊娠期高血压疾病患者设为观察组,196例设为对照组。分析妊娠期糖尿病合并妊娠期高血压疾病患者血清FABP4、OPG、CysC、AngⅡ的表达及其与空腹血糖的相关性,并分析以上指标对妊娠期糖尿病合并妊娠期高血压的诊断价值。结果:观察组患者血清FABP4、OPG、CysC、AngⅡ、空腹血糖水平均显著高于对照组(P0.05)。妊娠期糖尿病合并妊娠期高血压患者血清FABP4、OPG、CysC、AngⅡ、空腹血糖水平显著低于轻度子痫前期、重度子痫前期患者;轻度子痫前期患者以上指标水平显著低于重度子痫前期患者(P0.05)。血清FABP4、OPG、CysC、AngⅡ和空腹血糖之间均呈显著正相关(P0.05)。FABP4、OPG、CysC、AngⅡ诊断妊娠期糖尿病合并妊娠期高血压疾病的AUC分别为0.648、0.654、0.898、0.913,95%CI分别为0.576～0.719、0.586～0.722、0.854～0.943、0.886～0.941,以上指标联合检测诊断妊娠期糖尿病合并妊娠期高血压疾病的AUC为0.996,95%CI为0.992～1.000,单独检测分别和联合检测曲线下面积比较均具有显著差异(Z=9.569、9.669、4.115、6.310,P0.05);联合检测诊断妊娠期糖尿病合并妊娠期高血压疾病的特异度、准确度分别为94.17%、94.28%。结论:妊娠期糖尿病合并妊娠期高血压疾病患者血清FABP4、OPG、CysC、AngⅡ的表达均与空腹血糖存在显著正相关,以上四者联合检测诊断妊娠期糖尿病合并妊娠期高血压疾病时具有较高的临床价值。     

孕期营养与早发型子痫前期的关系

目的:探讨早发型子痫前期与孕期营养的关系,为早发型子痫前期的预防提供参考依据。方法:选择2011年10月~2013年10月我院收治的早发型子痫前期患者(发病孕周34周)60例为A组,晚发型子痫前期患者(发病孕周≥34周)58例为B组,以及同时期门诊产检孕周34周的正常孕妇40例为C组,产检孕周≥34周的正常孕妇40例为D组,检测和比较各组孕妇的血清总蛋白、血红蛋白含量、血细胞压积水平。结果:A组血清总蛋白、血红蛋白含量、血细胞压积均显著低于B和C组,差异均有统计学意义(P0.05);而C组血清总蛋白、血红蛋白含量、血细胞压积与D组比较无明显统计学差异(P0.05)。结论:早发型子痫前期的发生可能与孕期低蛋白血症、贫血相关,加强孕妇孕期的营养可能有助于预防早发型子痫前期的发生。     

Cyclin B1和p21在妊娠期高血压产妇胎盘组织中的表达及其临床意义

目的:观察CyclinB1和p21在妊娠期高血压产妇胎盘组织中的表达并探讨其临床意义.方法:采用免疫组化MaxVision法检测正常胎盘组织(20例)、妊娠期高血压胎盘组织(30例)、轻度子痫前期胎盘组织(30例)和重度子痫前期(30例)产妇胎盘组织中的cyclin B1和p21蛋白表达,并分析其与妊娠期高血压病情严重程度的相关性.结果:妊娠期高血压、轻度子痈前期、重度子痈前期胎盘组织中cyclinB1蛋白的表达均显著低于正常胎盘组织,差异均有统计学意义(P＜0.05),妊娠期高血压、轻度子痈前期、重度子痈前期胎盘组织中p21蛋白表达均显著高于正常胎盘组织,差异有统计学意义(P＜0.05).妊娠期高血压患者病情的严重程度与其胎盘组织中cyclinB1的蛋白表达呈显著负相关(r=0.641,P=0.000);而与其胎盘组织中p21蛋白的表达呈显著正相关(r=0.635,P=0.000).结论:Cyclin B1蛋白的表达下调和p21蛋白的表达上调可能参与了妊娠期高血压的发生发展,且二者在胎盘组织中的表达水平与妊娠期高血压病情的严重程度显著相关.     

低分子肝素对子痫前期大鼠炎症反应、肝功能及胎盘组织Bcl-2、Bax蛋白表达的影响

目的:研究低分子肝素对子痫前期大鼠炎症反应、肝功能及胎盘组织Bcl-2、Bax蛋白表达的影响。方法:将90只孕期大鼠以随机数表法分成正常孕组、子痫前期组、治疗组,每组30只。其中子痫前期组和治疗组大鼠于妊娠第13 d开始皮下注射左旋硝基精氨酸甲酯,建立子痫前期大鼠模型,注射剂量为200 mg/(kg·d),正常孕组予以等量生理盐水注射干预。治疗组予以低分子肝素皮下注射干预,注射剂量为40μL/(kg·d),子痫前期组以及正常孕组大鼠予以同等剂量的生理盐水注射处理。比较三组大鼠的血压、24 h蛋白尿,肝功能指标水平,血清炎症因子水平,胎盘组织中Bcl-2及Bax蛋白表达水平。结果:子痫前期组及治疗组大鼠妊娠第15 d、21 d时的血压水平均显著高于正常孕组,且妊娠第21 d时的24 h蛋白尿高于正常孕组,治疗组大鼠妊娠第21 d的血压及24 h蛋白尿均低于子痫前期组(均P<0.05)。妊娠第21 d时子痫前期组、治疗组大鼠的谷丙转氨酶(ALT)、谷草转氨酶(AST)、白细胞介素-2(IL-2)、白细胞介素-6(IL-6)、γ-干扰素(IFN-γ)水平均显著高于正常孕组,且治疗组低于子痫前期组(均P<0.05)。子痫前期组、治疗组大鼠胎盘组织中Bcl-2蛋白表达水平显著低于正常孕组,Bax蛋白表达水平显著高于正常孕组,且治疗组大鼠Bcl-2蛋白表达水平显著高于子痫前期组,Bax蛋白表达水平显著低于子痫前期组(均P<0.05)。结论:低分子肝素对子痫前期大鼠中具有明显的降血压效果,有利于改善大鼠肝功能,其主要作用机制可能与诱导Th1/Th2的平衡朝Th2方向发展,调节Bcl-2/Bax平衡有关。     

血脂代谢指标及血清维生素A、E水平与子痫前期的相关性分析

目的:探讨血脂代谢指标及血清维生素A、E水平与子痫前期的相关性。方法:选取2016年12月至2017年12月期间来我院产检及住院分娩的722例妊娠妇女,选取94例子痫前期的妊娠妇女作为A组,其中轻度子痫前期32例作为A1组,重度子痫前期62例作为A2组,并从剩余的628例正常妊娠者中选取126例自愿参与本研究的妊娠妇女作为B组。收集并记录妊娠妇女的临床指标,包括入院时的孕周、孕次、产次、流产次数、血脂代谢指标、血清维生素A、E水平,分析血脂代谢指标、血清维生素A、E水平与子痫前期的相关性。结果:三组孕妇总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白(LDL)、高密度脂蛋白(HDL)、载脂蛋白A(ApoA)、载脂蛋白B(ApoB)、维生素A、维生素E水平整体比较差异均具有统计学意义(均P0.05);A1组、A2组的TC、TG、LDL、HDL、ApoA、ApoB、维生素A、维生素E水平与B组比较,差异均有统计学意义(均P0.05),A2组TG、LDL高于A1组,而维生素A、维生素E水平低于A1组,差异均有统计学意义(均P0.05),Spearman秩相关分析结果显示,TC、TG、LDL、ApoB水平与子痫前期呈正相关(r=0.214,0.432,0.517,0.226,P=0.012,0.008,0.005,0.012),HDL、ApoA、维生素A、维生素E水平与子痫前期呈负相关(r=-0.282,-0.357,-0.539,-1.217,P=0.010,0.009,0.003,0.000)。结论:血脂代谢指标、维生素A、维生素E水平在子痫前期孕妇中表达异常,且这些指标与子痫前期密切相关,应重视妊娠期孕妇的血脂代谢指标、维生素A、维生素E水平的监测,并控制其水平,从而有效防治子痫前期。     

NLRP3炎症小体表达与慢性阻塞性肺疾病合并肺癌的相关性研究

目的:分析核苷酸结合寡聚化结构域样受体蛋白3(NLRP3)炎症小体表达与慢性阻塞性肺疾病(COPD)合并肺癌的相关性。方法:选取2015年1月-2018年2月我院收治的COPD合并肺癌患者62例作为实验组及同期88例COPD患者作为对照组。酶联免疫吸附法(ELISA)检测两组患者外周血IL-1β、IL-18浓度,免疫组化法检测两组患者术后肺病理组织中Caspase-1、ASC、NLRP3、IL-1β、IL-18蛋白相对表达量,并比较不同病理特征下患者术后肺病理组织中NLRP3、ASC、Caspase-1、IL-1β、IL-18蛋白相对表达量的差异,并分析其与COPD合并肺癌的相关性。结果:实验组患者外周血IL-1β、IL-18水平均明显高于对照组,差异具有统计学意义(P0.05);实验组患者术后肺病理组织中NLRP3、ASC、Caspase-1、IL-1β、IL-18蛋白相对表达量均明显高于对照组,差异均具有统计学意义(P0.05);中低分化、临床分期Ⅲ期、淋巴结有转移的急性加重期COPD合并肺癌患者术后肺病理组织中NLRP3、ASC、Caspase-1、IL-1β、IL-18蛋白相对表达量高于高分化、临床分期Ⅰ-Ⅱ期、淋巴结无转移的稳定期COPD合并肺癌患者,差异具有统计学意义(P0.05)。经Spearman秩相关性分析发现,患者术后肺病理组织中NLRP3、ASC、Caspase-1、IL-1β、IL-18蛋白相对表达量与COPD合并肺癌患者病情严重程度、淋巴结转移情况、分化程度以及病情所处时期均呈正相关(r0,P0.05)。结论:NLRP3炎症小体通路可能参与了COPD合并肺癌的发展过程,其释放的细胞因子IL-1β、IL-18水平升高可能与患者持续炎症有关,并进一步导致机体免疫病理损伤,促进疾病进展。     

妊娠高血压综合征患者血清瘦素水平变化及意义

目的探讨妊娠高血压综合征(妊高征)患者血清瘦素含量的变化及其在妊高征发病中的意义。方法采用放射免疫分析法(R IA)测定50例妊高征患者(HDP组,其中妊娠期高血压组12例,轻度子痫前期组20例,重度子痫前期组18例)、50例正常晚孕妇女(对照组)患者血清瘦素。结果 HDP组的血清瘦素值(24.23±7.94)μg/L显著高于对照组(10.12±3.15)μg/L(P<0.001),以子痫前期组增高明显。结论血清瘦素水平与妊高征的发生和病情程度有关。     

脐动脉血流对预测子痫前期新生儿和产妇结局的价值分析

目的:探讨应用脐动脉血流用于预测子痫前期新生儿和产妇结局的临床价值。方法:选择在我院产科建档分娩的120例孕产妇作为研究对象,根据子痫前期发病情况分为子痫前期组60例与对照组60例,记录和比较两组孕产妇的一般资料、血脂、血糖水平、分娩前脐动脉血流与新生儿体重、胎盘的重量及Apgar评分,并进行相关性与危险因素分析。结果:两组孕产妇的年龄、孕次、产次、流产次数、孕周等对比差异均无统计学意义(P0.05)。子痫前期组的血清HDL-C水平低于对照组(P0.05),血清TC、TG、LDL-C、FBG水平高于对照组(P0.05)。与对照组比较,子痫前期组脐动脉S/D、RI与PI值显著升高(P0.05)。所有孕产妇都顺利完成分娩,孕产妇与新生儿都存活,子痫前期组的新生儿出生体重及Apgar评分和胎盘的重量均显著低于对照组(P0.05)。在子痫前期组中,脐动脉S/D、RI、PI值与新生儿出生体重呈现显著负相关性(P0.05)。多重线性回归分析显示子痫前期孕产妇的脐动脉S/D、RI、PI值为影响新生儿出生体重的独立危险因素(P0.05)。结论:脐动脉血流与子痫前期新生儿出生体重显著相关,脐动脉S/D、RI、PI值为影响新生儿出生体重的独立危险因素,子痫前期脐动脉血流监测可为预测新生儿和产妇结局以及预后提供参考。     

慢性高血压合并妊娠发生子痫前期的危险因素分析

目的:探讨慢性高血压合并妊娠发生子痫前期的危险因素,为筛查慢性高血压孕妇合并子痫前期提供参考依据。方法:选取2009年3月~2013年7月我院收治的慢性高血压妊娠患者116例,根据是否合并子痫前期分为慢性高血压合并妊娠组(NHDP组)和慢性高血压合并子痫前期组(HDP组),比较两组患者不同孕期的血压、尿蛋白水平以及血液生化检测指标间的差异。结果:两组间年龄、孕次、孕前尿蛋白水平、孕早期及孕中期的平均动脉压、尿蛋白水平间差异均无统计学意义(P0.05)。HDP组孕前体质指数、孕晚期的平均动脉压、尿蛋白水平、Hb、UA、LDH、FDP均较NHPD组显著升高(P0.05),两组间Plt水平差异无统计学意义(P0.05)。logistic回归分析发现Hb、UA及FDP是慢性高血压妊娠患者并发子痫前期的危险因素。结论:凝血状况、血清尿酸水平及肾功能变化是慢性高血压合并妊娠者发生子痫前期的危险因素。     

NLRP3炎症小体的负向调控机制

NLRP3炎症小体是由NOD样受体(NOD-like receptor, NLR) NLRP3、接头蛋白ASC和胱冬肽酶-1(Caspase-1)所形成的多聚蛋白复合体,能够感受来自病原微生物的病原相关分子模式(pathogen-associated molecular patterns, PAMPs)和胞内自身危险信号-危险相关分子模式(danger-associated molecular patterns, DAMPs),促进细胞因子IL-1β和IL-18的成熟和分泌、引起细胞焦亡,从而在多种生理、病理过程中发挥重要作用. NLRP3炎症小体是目前研究最深入的炎症小体,其表达水平和活化强度与多种疾病的发生、发展密切相关,如感染性疾病、痛风、Ⅱ型糖尿病、动脉粥样硬化、阿尔兹海默症及癌症等.因此,阐明NLRP3炎症小体活化的调控机制,对于揭示这些疾病发生、发展的机理,寻找免疫调节治疗的新途径具有重要意义.本文详细介绍了NLRP3炎症小体的负向调控机制.     

Endogenous and Uric Acid-Induced Activation of NLRP3 Inflammasome in Pregnant Women with Preeclampsia

Preeclampsia (PE) is a specific syndrome of pregnancy, characterized by hypertension and proteinuria. This pathology is associated with hyperuricemia and elevated serum levels of inflammatory cytokines. Uric acid crystals may activate an intracellular complex called inflammasome, which is important for processing and release of inflammatory cytokines. This study investigated the state of monocyte activation, both endogenous and stimulated with monosodium urate (MSU), by gene expression of NLRP1 and NLRP3 receptors as well as their association with inflammatory cytokines expression. Monocytes were obtained from peripheral blood of 23 preeclamptic pregnant women, 23 normotensive pregnant women (NT) and 23 healthy non-pregnant women (NP). Inflammasome activation was evaluated by the gene expression of NLRP1, NLRP3, caspase-1, IL-1β, IL-18 and TNF-α by RT-qPCR in unstimulated monocytes (endogenous expression), or after cell stimulation with MSU (stimulated expression). The concentration of cytokines was assessed by ELISA. In preeclamptic pregnant women, gene expression of NLRP1, NLRP3, caspase-1, IL-1β and TNF-α by monocytes stimulated or not with MSU was significantly higher than in NT and NP groups. Stimulation of monocytes from preeclamptic and non-pregnant women with MSU induced increased gene expression of NLRP3, caspase-1 and TNF-α in relation to the endogenous expression in these groups, while this was not observed in the NT group. The cytokine determination showed that monocytes from women with PE produced higher endogenous levels of IL-1β, IL-18 and TNF-α compared to the other groups, while the stimulus with MSU led to higher production of these cytokines in preeclamptic group than in the NT group. In conclusion, the results showed increased basal gene expression of NLRP1 and NLRP3 receptors in monocytes from PE group. These cells stimulation with MSU demonstrates that uric acid plays a role in NLRP3 inflammasome activation, suggesting the participation of this inflammatory complex in the pathogenesis of preeclampsia.     

降浊四妙散通过降低血尿酸水平及抑制NLRP3炎症小体对大鼠高尿酸血症及其肾损伤的改善作用研究

摘要 目的：探究降浊四妙散通过降低血尿酸水平及抑制NLRP3炎症小体对大鼠高尿酸血症及其肾损伤的改善作用。方法：将28只SD大鼠随机分为对照组、氧酸钾（OA）模型组、OA+SMS组、OA+别嘌醇组,其中,SMS的剂量基于实验动物物质管理标准（每公斤体重成人剂量的10倍）;别嘌醇溶解在OA+别嘌醇组的饮用水中（浓度,150 mg/L）;对照组和OA组给予等量的蒸馏水（胃内容量控制在2 mL/d）,持续7周。探讨SMS对肾线粒体活性氧(ROS)和氧化应激(OS)产物、NLRP3-ASC-caspase-1轴的蛋白表达。结果：（1）对照组、OA模型和治疗组的数据存在显著差异（P<0.05）。在第7周结束时,模型组总尿酸排泄量显著高于对照组（P<0.05）,SZF组和别嘌醇组显著高于OA组（P<0.05）。（2）与对照组相比,OA组的BUN和Scr水平显著升高（P<0.05）,而接受SMS和别嘌醇治疗大鼠的BUN和Scr水平下降（P<0.05）。（3）肾组织结构中,对于OA+SZF和OA+别嘌呤醇组,肾近端肾小管上皮细胞肿胀、空泡变性和炎性细胞浸润减少。（4）OA诱导的高尿酸血症大鼠肾组织中氧化应激指标均升高（P＜0.05）;即超氧化物歧化酶（SOD）、过氧化氢酶（CAT）和谷胱甘肽过氧化物酶之间存在显著的不平衡,而SMS和别嘌醇干预可显著回复以上氧化应激反应指标的动态平衡（P＜0.05）。（5）OA组大鼠肾组织中TXNIP mRNA和蛋白表达显著高于其他组（P<0.05）,而SMS和别嘌醇有效抑制TXNIP mRNA 和蛋白表达（P<0.05）;高尿酸血症大鼠NLRP3-ASC-caspase-1 轴中的mRNA和蛋白质表达升高（P<0.05）。SMS干预后组NLRP3-ASC-caspase-1轴的激活显著被抑制（P<0.05）。结论：SMS通过降低高尿酸血症实验大鼠肾脏中血尿酸水平,进而减轻肾损害,同时其可抑制线粒体ROS触发的NLRP3炎性体激活来减轻肾小管损伤和炎症浸润。     

Sarsasapogenin alleviates diabetic nephropathy through suppression of chronic inflammation by down-regulating PAR-1: In vivo and in vitro study

BackgroundSarsasapogenin (Sar) shows good effects on diabetic nephropathy (DN) through inhibition of the NLRP3 inflammasome, yet the potential mechanism is not well known.PurposeThis study was designed to explore the regulation of thrombin and/or its receptor protease-activated receptor 1 (PAR-1) on the NLRP3 inflammasome and NF-κB signaling in DN condition, and further expounded the molecular mechanism of Sar on DN.MethodsStreptozotocin-induced diabetic rats were treated by gavage with Sar (0, 20 and 60 mg/kg) for consecutive 10 weeks. Then urine and serum were collected for protein excretion, creatinine, urea nitrogen, and uric acid assay reflecting renal functions, renal tissue sections for periodic acid-Schiff staining and ki67 expression reflecting cell proliferation, and renal cortex for the NLRP3 inflammasome and NF-κB signaling as well as thrombin/PAR-1 signaling. High glucose-cultured human mesangial cells (HMCs) were used to further investigate the effects and mechanisms of Sar.ResultsSar markedly ameliorated the renal functions and mesangial cell proliferation in diabetic rats, and suppressed activation of the NLRP3 inflammasome and NF-κB in renal cortex. Moreover, Sar remarkably down-regulated PAR-1 in protein and mRNA levels but didn't affect thrombin activity in kidney, although thrombin activity was significantly decreased in the renal cortex of diabetic rats. Meanwhile, high glucose induced activation of the NLRP3 inflammasome and NF-κB, and increased PAR-1 expression while didn't change thrombin activity in HMCs; however, Sar co-treatment ameliorated all the above indices. Further studies demonstrated that PAR-1 knockdown attenuated activation of the NLRP3 inflammasome and NF-κB, and Sar addition strengthened these effects in high glucose-cultured HMCs.ConclusionSar relieved DN in rat through inhibition of the NLRP3 inflammasome and NF-κB by down-regulating PAR-1 in kidney.     

血清ghrelin、NLRP3对老年抑郁症患者认知功能损害的诊断价值分析

摘要 目的：分析血清胃促生长素（ghrelin）、Nod样受体热蛋白结构域相关蛋白3（NLRP3）对老年抑郁症患者认知功能损害的诊断价值。方法：选择2020年1月至2021年10月在我院接受诊治的老年抑郁症患者90例作为抑郁症组,另选取同期精神健康老年志愿者50例作为对照组。根据抑郁症病情严重程度将老年抑郁症患者分为轻度组（n=32）、中度组（n=30）、重度组（n=28）,比较不同分组研究对象血清ghrelin、NLRP3水平变化。另根据老年抑郁症患者是否发生认知功能损害分为认知功能损害组和认知功能未损害组,收集患者一般人口学及临床资料,分析影响老年抑郁症患者认知功能发生损害的危险因素。采用受试者工作特征（ROC）曲线分析血清ghrelin、NLRP3对老年抑郁症患者认知功能损害的诊断价值。结果：重度组血清NLRP3炎症小体水平明显高于中度组,中度组血清NLRP3炎症小体水平明显高于轻度组,轻度组血清NLRP3炎症小体水平明显高于对照组（P<0.05）;重度组血清ghrelin水平明显低于中度组,中度组血清ghrelin水平明显低于轻度组,轻度组血清ghrelin水平明显低于对照组（P<0.05）。多因素Logistic回归分析结果显示,重大生活事件（意外事故、破产、至亲去世等）、合并糖尿病、血清ghrelin水平、独居、血清NLRP3炎症小体水平以及社会支持是老年抑郁症患者认知功能损害的影响因素（P<0.05）。血清NLRP3炎症小体、ghrelin单独以及联合诊断老年抑郁症患者认知功能损害的曲线下面积AUC（0.95CI）分别为0.723（0.506～0.922）、0.782（0.619～0.917）、0.863（0.721～0.981）。结论：血清NLRP3炎症小体水平在老年抑郁症患者中呈高表达、ghrelin水平呈现低表达,二者均是老年抑郁症患者认知功能损害的影响因素,且联合检测二者水平可辅助诊断老年抑郁症患者认知功能损害。     

慢性牙周炎合并2型糖尿病患者龈沟液Sirtuin-1、Sirtuin-6的变化及临床价值研究

摘要 目的：探讨慢性牙周炎（CP）合并2型糖尿病（T2DM）患者龈沟液沉默信息调节因子-1（Sirtuin-1）、Sirtuin-6的变化和临床价值。方法：选择2020年3月至2023年3月中国人民解放军联勤保障部队第九七〇医院收治的147例CP合并T2DM患者（T2DM组）,128例单纯CP患者（CP组）和121例健康体检者（对照组）。根据牙周检查结果将T2DM组患者分为轻度组（n=49）、中度组（n=67）、重度组（n=31）。检测受试者龈沟液中Sirtuin-1、Sirtuin-6水平以及外周血单核细胞核苷酸结合寡聚化结构域样受体热蛋白结构域亚家族成员3（NLRP3）信使核糖核酸（mRNA）、程序性细胞死亡相关斑点样蛋白（ASC）mRNA、半胱氨酸蛋白酶1（Caspase-1）mRNA表达,并评估牙周临床指标。Pearson分析CP合并T2DM患者龈沟液Sirtuin-1、Sirtuin-6水平与牙周临床指标、外周血单核细胞NLRP3 mRNA、ASC mRNA、Caspase-1 mRNA表达的相关性。受试者工作特征（ROC）曲线分析龈沟液Sirtuin-1、Sirtuin-6诊断CP合并T2DM的价值。结果：T2DM组龈沟液Sirtuin-1、Sirtuin-6水平低于CP组和对照组（P＜0.05）,出血指数（SBI）、牙周袋探诊深度（PD）、牙龈指数（GI）、菌斑指数（PLI）、附着丧失（AL）、外周血单核细胞NLRP3 mRNA、ASC mRNA、Caspase-1 mRNA表达高于CP组和对照组（P＜0.05）。CP组龈沟液Sirtuin-1、Sirtuin-6水平低于和对照组（P＜0.05）,GI、SBI、PLI、PD、AL、外周血单核细胞NLRP3 mRNA、ASC mRNA、Caspase-1 mRNA表达高于对照组（P＜0.05）。重度组龈沟液Sirtuin-1、Sirtuin-6水平低于中度组和轻度组（P＜0.05）,GI、PLI、SBI、AL、PD、外周血单核细胞NLRP3 mRNA、ASC mRNA、Caspase-1 mRNA表达高于中度组和轻度组（P＜0.05）。中度组龈沟液Sirtuin-1、Sirtuin-6水平低于轻度组（P＜0.05）,GI、PLI、SBI、AL、PD、外周血单核细胞NLRP3 mRNA、ASC mRNA、Caspase-1 mRNA表达高于轻度组（P＜0.05）。CP合并T2DM患者龈沟液Sirtuin-1、 Sirtuin-6水平与GI、PLI、SBI、AL、PD、外周血单核细胞NLRP3 mRNA、ASC mRNA、Caspase-1 mRNA表达均呈负相关（P＜0.05）。龈沟液Sirtuin-1、 Sirtuin-6诊断CP合并T2DM的曲线下面积（AUC）为0.787、0.806,联合诊断AUC为0.912,高于单独诊断。结论：CP合并T2DM患者龈沟液中Sirtuin-1、Sirtuin-6水平降低,且与牙周组织破坏程度加重、NLRP3炎症小体激活有关。龈沟液Sirtuin-1联合Sirtuin-6在CP合并T2DM诊断中具有较高价值。     

高龄瘢痕子宫再妊娠孕产妇剖宫产术终止妊娠直接病因及预后影响因素分析

摘要 目的：探讨高龄瘢痕子宫再妊娠孕产妇剖宫产术终止妊娠直接病因及预后影响因素分析。方法：回顾性分析2016年1月-2020年10月在我院收治的400例高龄瘢痕子宫再妊娠孕妇。按照是否终止妊娠将400例孕妇分为终止妊娠组（200例）和未终止妊娠组（200例）。并对200例终止妊娠孕妇进行2年随访,按照2年内再妊娠情况分为再妊娠成功组（150例）和再次终止妊娠组（50例）。采用Spearman检验进行相关性分析;采用logistics回归模型进行回归分析。结果：200例终止妊娠孕妇中瘢痕妊娠60（30.00 %）例,死胎13（6.50 %）例,胎儿畸形25（12.50 %）例,子痫前期81（40.50 %）例,胎膜早破11（5.50%）例,妊娠意外事件10（5.00 %）例。高龄瘢痕子宫孕妇终止妊娠后再妊娠与教育水平、是否有固定职业、家庭月收入无关（P＞0.05）;与年龄、孕次、产次、剖宫产手术史、终止妊娠病因有关（P<0.05）;200例终止妊娠孕妇预后再妊娠与年龄、孕次、产次、剖宫产手术史、终止妊娠病因密切相关（P<0.05）;多因素分析结果显示,年龄、孕次、产次、剖宫产手术史、终止妊娠病因是独立危险因素（P<0.05）。结论：高龄瘢痕子宫孕妇终止妊娠的主要病因为瘢痕妊娠,死胎,胎儿畸形例,子痫前期,胎膜早破,妊娠意外事件。年龄、孕次、产次、剖宫产手术史、终止妊娠病因是影响高龄瘢痕子宫孕妇预后再妊娠的独立危险因素。     

Development of novel NLRP3-XOD dual inhibitors for the treatment of gout

Gout is a crystalline-related arthropathy caused by the deposition of monosodium urate (MSU). Acute gouty arthritis is the most common first symptom of gout. Studies have shown that NOD-like receptor protein 3 (NLRP3) inflammasome as pattern recognition receptors can be activated by uric acid crystallization, triggering immune inflammation and causing acute gouty arthritis symptoms. Currently, the treatment of gout mainly includes two basic methods: reducing uric acid and alleviating inflammation. In this paper, 22 novel benzoxazole and benzimidazole derivatives were synthesized from deoxybenzoin oxime derivatives. These compounds have good inhibitory effects on NLRP3 and XOD screened by our research group in the early stage. The inhibitory activities of XOD and NLRP3 and their derivatives were also screened. Notably, compound 9b is a multi-targeting inhibitor of NLRP3 and XOD with excellent potency in treating hyperuricemia and acute gouty arthritis.     

Upregulation of NLRP3 Inflammasome in the Tears and Ocular Surface of Dry Eye Patients

PurposeTo evaluate the mRNA and protein expressions of NLRP3 inflammasome and its downstream inflammatory factors in human dry eye.MethodsWe recruited 54 patients with Sjögren’s syndrome dry eye (SSDE), 50 patients with non-Sjögren’s syndrome dry eye (NSSDE), and 46 healthy controls. Tear film breakup time (TBUT), Schirmer I test, and fluorescein staining (FL) were performed on all subjects. Tear samples were obtained to analyze the inflammatory cytokine levels of IL-1β and IL-18 via enzyme-linked immunosorbent (ELISA). Conjunctival impression cytology (CIC) specimens were collected to detect the mRNA expression of NLRP3, caspase-1, IL-1β, and IL-18 using quantitative RT-PCR, and the protein expression of NLRP3 and caspase-1 by Western blotting.ResultsNLRP3 mRNA expression showed higher levels in both dry eye groups compared with controls, with a comparably significant elevation in the SSDE group (relative 2.47-fold upregulation, p<0.05). NLRP3 protein expression was also increased in SSDE group (relative1.94-fold upregulation) compared with the controls. mRNA expression of caspase-1 was significantly upregulated in both SSDE (relative 1.44-fold upregulation, p<0.05) and NSSDE (relative 1.32-fold upregulation, p<0.05). Procaspase-1 protein level was increased in SSDE (relative 1.84-fold upregulation) and NSSDE (relative 1.12-fold upregulation) versus controls; and caspase-1 protein expression was also increased in SSDE (relative 1.49-fold upregulation) and NSSDE (relative 1.17-fold upregulation) compared with the controls. The patients with SSDE and NSSDE had higher IL-1β and IL-18 mRNA values and protein expressions than the controls did. The relative mRNA expression of IL-1β upregulated 3.59-fold (p<0.001) in SSDE and 2.13-fold (p<0.01) in NSSDE compared with the controls. IL-1β protein level also showed significant upregulation in SSDE (p=0.01; vs. controls groups). IL-18 mRNA expression levels were significantly upregulated in the SSDE (relative 2.97-fold upregulation, p=0.001) and NSSDE (relative 2.05-fold upregulation, p=0.001) groups compared with the controls; tear IL-18 concentrations were also significantly increased in the SSDE (p<0.001) and NSSDE (p<0.05) groups.ConclusionsIn the current study, we found that mRNA and protein expressions of NLRP3 inflammasome were upregulated in human dry eyes, especially in SSDE; the downstream inflammatory factors caspase-1, IL-1β, and IL-18 were also elevated in dry eye patients. These observations suggest the involvement of NLRP3 inflammasome in the onset and development of the inflammation in dry eye.     

Acid‐sensing ion channels regulate nucleus pulposus cell inflammation and pyroptosis via the NLRP3 inflammasome in intervertebral disc degeneration

ObjectiveLactate accumulation is an important factor in the intervertebral disc degeneration (IVDD). Currently, the effect and underlying mechanism of action of lactate on nucleus pulposus (NP) cell inflammation during IVDD are unclear. Previous studies have found that the NLRP3 inflammasome plays an important role in the regulation of NP inflammation. This study focused on the regulation of acid‐sensitive ion channels (ASICs) in relation to inflammation and the effect of NLRP3 on pyroptosis levels in NP cells under acidic conditions.DesignFor the in vitro experiments, human NP cells were exposed to 6 mM lactate solution; different groups were either treated with NLRP3 inhibitor or transfected with siRNA against NLRP3, siRNA against ASC or a mix of these, and mRNA and protein expression levels were then assessed. For the in vivo experiment, varying concentrations of lactate were injected into rat intervertebral discs and examined via magnetic resonance imaging (MRI) and histological staining.ResultsExtracellular lactate promoted NLRP3 inflammasome activation and degeneration of the NP extracellular matrix; furthermore, it increased the levels of inflammation and pyroptosis in the NP. Lactate‐induced NLRP3 inflammasome activation was blocked by ASIC inhibitors and NLRP3 siRNA.ConclusionsExtracellular lactate regulates levels of intercellular reactive oxygen species (ROS) through ASIC1 and ASIC3. ROS activate the NF‐κB signalling pathway, thus promoting NLRP3 inflammasome activation and IL‐1β release, both of which promote NP degeneration.