Quercetin protects against cisplatin‐induced acute kidney injury by inhibiting Mincle/Syk/NF‐κB signaling maintained macrophage inflammation

Acute kidney injury (AKI) with high incidence and mortality is the main cause of chronic kidney disease. Previous studies have indicated that quercetin, an abundant flavonoid in plants, exhibited renoprotective role in AKI. However, the underlying mechanism is largely unknown. In this study, we try to explore whether quercetin protects against AKI by inhibiting macrophage inflammation via regulation of Mincle/Syk/NF‐κB signaling. The results demonstrated that quercetin can significantly inhibit expression and secretion of IL‐1β, IL‐6, and TNF‐α in LPS‐induced bone marrow‐derived macrophages (BMDMs) and reduce activity of Mincle/Syk/NF‐κB signaling in vitro. We also found that quercetin can strongly reduce the concentration of serum creatinine, BUN, IL‐1β, IL‐6, and TNF‐α in cisplatin‐induced AKI model. Furthermore, quercetin down‐regulated protein levels of Mincle, phosphorylated Syk and NF‐κB in kidney macrophages of AKI, as well as inhibited M1, up‐regulated M2 macrophage activity. Notably, the down‐regulation of LPS‐induced inflammation by quercetin was reversed after adding TDB (an agonist of Mincle) in BMDMs, suggesting that quercetin suppresses macrophage inflammation may mainly through inhibiting Mincle and its downstream signaling. In summary, these findings clarified a new mechanism of quercetin improving AKI‐induced kidney inflammation and injury, which provides a new drug option for the clinical treatment of AKI.     

探讨氨甲环酸在老年股骨转子间骨折围手术期应用安全性及有效性分析

目的探讨氨甲环酸(tranexamic acid,TXA)降低老年股骨转子间骨折围术期失血量的安全性及有效性。方法按照随机数字表法将2016年3月至2018年1月收治的200例老年股骨转子间骨折患者分为A、B、C、D组,每组50例。A组为对照组,共50例,其中男22例,女28例,平均年龄(77.74±6.53)岁,骨折按AO/OTA分型:A型17例,B型19例,C型14例。B组术前30 min静滴TXA 1 g,共50例,其中男27例,女23例,平均年龄(79.25±6.55)岁,骨折按AO/OTA分型:A型19例,B型15例,C型16例。C组术毕在骨折断端筋膜处注射TXA 1 g,共50例,其中男19例,女31例,平均年龄(74.35±5.97)岁,骨折按AO/OTA分型:A型13例,B型22例,C型15例。D组术前30 min静滴TXA 1 g,术毕在骨折断端筋膜处注射TXA 1 g,共50例,其中男24例,女26例,平均年龄(76.62±6.21)岁,骨折按AO/OTA分型:A型21例,B型18例,C型11例。记录各组总失血量、隐形失血量;术后1天和3天血红蛋白、红细胞压积、D-二聚体及纤维蛋白原、并发症发生率及输血率。结果B组(815.33±278.79)ml、C组(935.15±207.54)ml、D组(795.56±243.18)ml的总失血量低于A组(1096.88±223.79)ml,各组相比差异有统计学意义(P=0.024);B组(501.95±260.72)ml、C组(679.22±215.64)ml、D组(456.18±215.64)ml的隐性失血量低于A组(832.60±253.41)ml,各组相比差异有统计学意义(P=0.005);术后1天B组(110.84±11.73)g/L、C组(105.26±13.70)g/L、D组(109.40±13.81)g/L的血红蛋白值均高于A组(103.68±10.85)g/L,各组相比差异有统计学意义(P=0.014)。与C组相比,B组与D组在降低围术期总失血量和隐性失血量更有效果。术后3天四组的血红蛋白、红细胞压积、D-二聚体、纤维蛋白原、术后下肢深静脉血栓发生率及切口并发症发生率相比差异无统计学意义(P>0.05)。所有患者均无肺栓塞发生。结论老年转子间骨折患者围术期使用TXA均可降低围术期总失血量和隐性失血量,对术后康复有一定的积极作用,且不增加深静脉血栓发生率,静脉或联合应用效果更优。     

儿童肺炎金黄色葡萄球菌分离株的分子生物学特征及耐药性研究

目的了解儿童金黄色葡萄球菌(金葡菌)肺炎致病株分子特征及耐药性,供临床诊治参考。方法收集2016年1月至2017年3月首都医科大学附属北京儿童医院确诊为金葡菌肺炎患者分离株,采用头孢西丁纸片法和mecA检测鉴定耐甲氧西林金葡菌(MRSA)或甲氧西林敏感金葡菌(MSSA);对所有菌株进行多位点序列分型(MLST)和葡萄球菌蛋白A(spa)分型,并对MRSA菌株进行葡萄球菌盒氏染色体(SCCmec)分型;采用PCR方法检测21种超抗原(SAgs)基因、杀白细胞素(PVL)基因、黏附基因fnbB、cna;采用琼脂稀释法、E-test检测14种抗生素体外药物敏感性。结果共收集42株金葡菌,其中MRSA、MSSA各21株。MRSA的优势克隆为ST59-SCCmecⅣa-t437(71.4%);MSSA的分型较为分散,以ST25-t078(14.2%)最多见。42株金葡菌中有36株(85.7%)至少携带1种超抗原基因,最常见的超抗原基因型为sek-seq(21.4%);MRSA pvl基因携带率(52.3%)明显高于MSSA(14.2%),而MSSA fnbB及cna基因携带率(42.8%和47.6%)明显高于MRSA(均为9.5%),差异均有统计学意义(均P<0.05)。本组金葡菌多重耐药率达90.4%(38/42株)。结论MRSA在儿童金葡菌肺炎致病株中检出率高,其主要克隆型为ST59-SCCmecⅣa-t437。儿童肺炎金葡菌分离株的超抗原基因携带率和多重耐药率较高,MRSA菌株常携带pvl基因,而MSSA菌株携带fnbB、cna更常见。     

桃红四物汤化学成分、药理作用、临床应用的研究进展及质量标志物的预测分析

桃红四物汤,活血祛瘀之经典名方。该文对近年来桃红四物汤的化学成分、药理作用以及临床应用研究进展进行总结与分析。目前,桃红四物汤不同提取部位化学成分的研究较为系统,其药理作用研究主要集中在活血化瘀、调经镇痛、促进骨折愈合等方面,临床可应用于多系统、多脏腑疾病的治疗,例如妇科疾病、内科疾病、骨伤科疾病、皮肤科疾病等。在此基础上,依照质量标志物(Q-marker)有效、特有、传递与溯源、可测和处方配伍的"五原则"对桃红四物汤Q-marker进行预测分析,提示阿魏酸、芍药苷、苦杏仁苷、芍药内酯苷、梓醇、没食子酸、羟基红花黄色素A可作为该复方的Q-marker,后续可选择这些Q-marker为指标,根据药材、饮片、中间体、对应实物的量值传递进行桃红四物汤全程质量控制并创建其质量可溯源体系。     

Next-generation sequencing through multigene panel testing for the diagnosis of hereditary epidermolysis bullosa in Chinese population

Epidermolysis bullosa (EB) is a heritable blistering disorder. We performed a next-generation sequencing-based multigene panel test and successfully predicted 100% of the EB types, including, 36 EB simplex (EBS), 13 junctional EB (JEB), 86 dystrophic EB (DEB), and 3 Kindler EB. Chinese JEB and recessive DEB (RDEB) patients have relatively mild phenotypes; for severe type separately accounts for 45.5% and 23.8%, respectively. We identified 96 novel and 49 recurrent pathogenic variants in 11 genes, although we failed to detect the second mutation in one JEB and five RDEB patients. We identified one novel p.E475K mosaic mutation in the clinically normal mother of one out of 13 EBS patients with KRT5 mutations, one recurrent p.G2034R mosaic mutation, and one novel p.G2043R mosaic mutation in the clinically normal relatives of two out of 19 dominant DEB patients. This study shows that next-generation technology could be an effective tool in diagnosing EB.     

蒙药朱日亨滴丸源头把控——基于Q-Exactive高分辨质谱结合指纹图谱技术的蒙药广枣药材质量评价研究

目的 运用Q-Exactive高分辨质谱结合指纹图谱评价不同批次广枣药材质量,为朱日亨滴丸源头把控提供参考。方法 采用Agilent ZORBAX ECLIPSE XDB-C18色谱柱,以0.1%甲酸水-甲醇梯度洗脱30min,柱温为30℃,流速为1.0ml.min^-1。采用电喷雾(ESI)质谱离子源,在正离子与负离子模式下采集数据,检测范围为m/z 100-1500。依据精确质量数以及二级碎片离子,结合标准物质及相关数据库信息,对蒙药广枣药材主要化学成分进行定性研究。同时测定10批广枣药材,应用“中药色谱指纹图谱相似度评价系统(2004A)”建立广枣指纹图谱,并对各共有峰进行化学成分归属,对鞣花酸进行定量,评价各批次药材的质量。结果 鉴定出广枣中的37种化合物,并以鞣花酸为参照物,建立广枣药材指纹图谱,10批次广枣药材相似均在0.90以上。不同批次广枣药材鞣花酸含量差异明显。结论 建立基于Q-Exactive高分辨质谱结合指纹图谱技术的蒙药广枣药材质量评价研究方法为广枣药材质量控制提供参考,也为主日亨滴丸源头保证提供科学依据。     

肠愈宁颗粒对溃疡性结肠炎大鼠部分免疫机制的影响

目的:研究不同剂量的肠愈宁颗粒对溃疡性结肠炎(UC)模型大鼠结肠血清白细胞介素-1β(IL-1β)、肿瘤坏死因子-α(TNF-α)和白细胞介素-4(IL-4)表达的影响,阐述其抗UC的免疫机制。方法:48只雄性Wistar大鼠平均随机分成6组:空白对照组、模型组、肠愈宁高剂量组、肠愈宁中剂量组、肠愈宁低剂量组、美沙拉嗪对照组。应用三硝基苯磺酸(TNBS)/乙醇复合灌肠法诱导UC大鼠模型,评估疾病活动指数(DAI),结肠黏膜损伤指数(CMDI)并进行组织损伤指数(TDI)评分,酶联免疫吸附测定法(ELISA)检测大鼠IL-1β、TNF-α、IL-4的变化。结果:注入5% TNBS 50 mg/kg＋50%乙醇0.25 mL连续1周可成功导致大鼠患上溃疡性结肠炎(UC),肠愈宁颗粒可对抗5% TNBS 50 mg/kg＋50%乙醇所致的大鼠UC,与模型组比较,加入肠愈宁高剂量组、肠愈宁中剂量组的DAI、CMDI和TDI评分均降低,IL-1β、TNF-α表达下调,IL-4表达上调。结论:肠愈宁颗粒抵抗溃疡性结肠炎(UC)的作用显著,其机制可能与下调促炎因子TNF-α以及白细胞介素IL-1β的表达,上调促炎因子IL-4的表达有关。