脉血康胶囊联合瑞舒伐他汀对冠脉临界病变患者冠脉病变程度的影响

目的研究脉血康胶囊联合瑞舒伐他汀对冠脉临界病变患者钙库操纵性钙通道蛋白(SOCC)基质交联分子1(STIM1)、钙释放激活钙通道蛋白Orai1及瞬时受体电位通道1(TRPC1)蛋白水平和冠脉病变严重程度的影响。方法将2015年1月—2016年12月北京安贞医院经定量冠脉造影检查确诊冠脉临界病变(BCL)住院患者160例设为临界病变组(BCL组),150例无冠脉病变的受试者为对照组(简称CTR组)。BCL组随机分为常规治疗组(简称RTT组,80例)和联合治疗组(简称CBT组,80例)。RTT组给予生活方式改善、阿司匹林、AECI、β受体阻滞剂及瑞舒伐他汀10 mg等药物。CBT组在常规药物治疗基础上,每日加用瑞舒伐他汀15 mg和脉血康胶囊3.0 g,连续治疗12个月。检测血小板STIM1、Orai1、TRPC1、高敏C-反应蛋白(hs-CRP)水平及TC、LDL-C、HDL-C、TG浓度。评价BCL组平均狭窄程度(MPS)。结果BCL组130例受试者复查冠脉造影。与本组治疗前比较,治疗后CBT组和RTT组血小板STIM1、Orai1、TRPC1水平均降低(P<0.05);CBT组冠脉临界病变的MPS明显减低(59.74±9.72vs.38.92±13.84,P<0.05),RTT组MPS有所下降(58.96±8.67vs.55.43±10.03),但差异无统计学意义(P>0.05)。与RTT组比较,治疗后CBT组血小板STIM1、Orai1、TRPC1、TC、LDL-C、TG、和hs-CRP明显降低(P<0.05,P<0.01),且CBT组MPS差值大于RTT组(P<0.01)。结论脉血康胶囊3.0 g和瑞舒伐他汀15 mg每日联合应用可降低SOCC水平,其可能是冠脉临界病变治疗的优化选择。     

真菌性、细菌性和病毒性肺炎的若干凝血指标变化分析

探讨真菌性、细菌性和病毒性肺炎的若干凝血指标差异性研究。方法 回顾性分析2017 年7 月～2019 年11 月本院肺炎患者128 例与同期门诊健康体检者50 例，分析患者血浆纤维蛋白原（FIB）、凝血酶原时间（PT）和活化部分凝血酶时间（APTT）的水平。结果 三类肺炎组与对照组在FIB、PT 和APTT 水平比较，差异均有统计学意义（P＜0.01）；FIB、PT 水平与病原感染呈正相关，APTT 与病原感染呈负相关。结论FIB、PT、APTT 可以间接提示肺炎感染病原体类型，具有临床意义。     

Successful treatment of linezolid-induced severe lactic acidosis with continuous venovenous hemodiafiltration: A case report

Linezolid is an oxazolidinone antibiotic. Linezolid-associated lactic acidosis has been reported in 6.8% of linezolid-treated patients. Lactic acidosis is associated with poor clinical outcomes, with high blood lactate levels resulting in organ dysfunction and mortality. This case report describes the development of lactic acidosis in a 64-year-old Chinese woman who had received 33 days of treatment with antituberculosis drugs and 28 days of treatment with oral linezolid for tuberculous meningitis. Severe lactic acidosis was reversed by withdrawing antituberculosis drugs and using continuous venovenous hemodiafiltration (CVVH). When the patient's condition was stable, she was transferred to the infectious disease department, and antituberculosis drugs, with the exception of linezolid, were reintroduced. This did not result in recurrence of lactic acidosis. The causal relationship between lactic acidosis and linezolid was categorized as ‘probable’ on the Adverse Drug Reaction Probability Scale. This case demonstrates that CVVH has potential as an alternative to discontinuation of linezolid alone for rapid reversal of linezolid-associated severe lactic acidosis.     

Procoagulant profile in patients with immune thrombocytopenia

Despite their low platelet count some immune thrombocytopenia (ITP) patients seldom bleed, indicating the presence of factors to compensate thrombocytopenia. Moreover, ITP patients may have an increased risk for thrombosis. These facts suggest the presence of procoagulant mechanisms that have not been clarified yet. The aim of this study was to identify these possible factors. Moreover, the utility of rotational thromboelastometry (ROTEM^®) to test haemostasis in these patients was also evaluated. Patients with ITP presented a procoagulant profile due to an increased amount of platelet‐ and red cell‐microparticles, an increased resistance to protein C and the formation of a clot more resistant to fibrinolysis due to augmented levels of plasminogen activator inhibitor‐1, which might reflect an endothelial damage/activation in ITP patients. Despite increased maximum clot firmness and reduced lysis, ROTEM^® profiles showed a prolonged clotting time that might rely on the presence of anti‐platelet antibodies as suggested by the increased lagtime in thrombin generation test caused by plasma from ITP patients on platelets from healthy controls. These results indicate the need to individualize therapeutic treatment for ITP patients, considering their procoagulant profile and the presence of concomitant risk factors. Moreover, ROTEM^® appeared to be useful for evaluating haemostasis in ITP patients.     

The role of extracellular histones in haematological disorders

Over the past decades, chromosomal alterations have been extensively investigated for their pathophysiological relevance in haematological malignancies. In particular, epigenetic modifications of intra‐nuclear histones are now known as key regulators of healthy cell cycles that have also evolved into novel therapeutic targets for certain blood cancers. Thus, for most haematologists, histones are DNA‐chained proteins that are buried deep within chromatin. However, the plot has deepened with recent revelations on the function of histones when unchained and released extracellularly upon cell death or from activated neutrophils as part of neutrophil extracellular traps (NETs). Extracellular histones and NETs are increasingly recognized for profound cytotoxicity and pro‐coagulant effects. This article highlights the importance of recognizing this new paradigm of extracellular histones as a key player in host defence through its damage‐associated molecular patterns, which could translate into novel diagnostic and therapeutic biomarkers in various haematological and critical disorders.     

Expression and activity of thrombomodulin in human gingival epithelium: in vivo and in vitro studies

Epidermal keratinocytes thrombomodulin (TM) has been shown to regulate thrombin at sites of cutaneous injury in addition to a role for epidermal differentiation. TM, a major anticoagulant proteoglycan of the endothelial cell membrane, is a thrombin receptor that acts as a co‐factor for protein C activation. Thrombin has pro‐inflammatory effects for periodontitis. However, little is known about TM in gingival tissue with periodontitis. We used immunohistochemistry to examine expression of TM in gingival epithelium from patients with periodontitis. In vitro , we observed TM expression at varying Ca²⁺ concentrations by confocal laser scanning microscopy, examined the expression of TM mRNA and tested TM co‐factor activity. Furthermore, we measured TM concentration in gingival crevicular fluid (GCF) from 11 severe adult cases of periodontitis using enzyme‐linked immunosorbent assay. Immunoreactive TM was present in gingival epithelium and junctional epithelium, and was reduced in inflamed gingival epithelium compared to healthy gingival epithelium. Ultrastructurally, TM, including microvilli, was observed on the cell membrane. TM localization in cells cultured in 0.09 m m Ca²⁺ differed from that in cells exposed to 1.2 m m Ca²⁺. Northern analysis demonstrated TM mRNA in gingival keratinocytes more than in human umbilical vein endothelial cells (HUVEC). Gingival keratinocytes also facilitated protein C activation by thrombin, although less strongly than HUVEC. TM in GCF at sites with bleeding on probing in patients was significantly elevated ( p <0.001, Student's t ‐test). TM in gingival epithelium may regulate thrombin activity at sites of coagulation and inflammation with periodontal disease, although inflammation may impair this regulation of thrombin.