Inter-ictal assay of peripheral circulating inflammatory mediators in migraine patients under adjunctive cervical non-invasive vagus nerve stimulation (nVNS): A proof-of-concept study

Objective

To assay peripheral inter-ictal cytokine serum levels and possible relations with non-invasive vagus nerve stimulation (nVNS) responsiveness in migraineurs.

HBV-ACLF患者血清miR-122和 HMGB1水平及其与病情、预后的关系

[摘要]　目的　探究HBV相关慢加急性肝衰竭（HBV-related acute-on-chronic liver failure, HBV-ACLF）患者血清中微小核糖核酸（microRNA, miR）-122和高迁移率族蛋白1（high-mobility group box-B1, HMGB1）水平及其与病情、预后的关系。方法　回顾性分析2016年1月—2018年1月我院收治的120例HBV-ACLF患者的一般及临床资料。根据临床结局，将患者分为存活组（53例）和死亡组（67例）。比较2组患者的一般资料、实验室检查指标及血清miR-122、HMGB1水平。多因素Logistic回归分析影响患者预后的因素。Pearson检验分析miR-122、HMGB1水平分别与TBIL、PA、终末期肝病评分模型（the model of end-stage liver disease score, MELD）评分的相关性。ROC曲线分析miR-122和HMGB1水平对患者的死亡预测价值，获得最佳临界值。根据临界值将患者分为A组、B组和C组，用Kaplan-Meier法绘制生存曲线，比较3组患者在3年随访期间的生存率。结果　存活组和死亡组患者的年龄、身体质量指数、并发症、病情分期、MELD评分、ALB、球蛋白、TBIL、ALT、AST、LDH、PT、PTA、HBV DNA、miR-122、HMGB1相比，差异均具有统计学意义（P均＜0.05）。年龄、并发症、病情分期、MELD评分、TBIL、PT、PTA、miR-122、HMGB1均是影响患者预后的危险因素（P均＜0.05）。miR-122、HMGB1水平分别与TBIL、MELD评分呈显著正相关，与PTA呈显著负相关（P均＜0.05）。miR-122和HMGB1预测患者死亡的最佳临界值分别为31.42和14.56 μg/L。A组患者预后3年内生存率显著高于B组和C组（P均＜0.05）。结论　miR-122和HMGB1水平与HBV-ACLF患者的病情和死亡预后密切相关，可间接反映患者的病情严重程度，在HBV-ACLF的诊断及预后中具有重要价值。     

枸橼酸咖啡因与氨茶碱对早产儿不同时相血糖值的影响比较

目的观察并比较枸橼酸咖啡因及氨茶碱对早产儿不同时相血糖的影响程度。方法选择新生儿监护室诊断为原发性呼吸暂停的出生胎龄＜34周的早产儿172例，采用随机数字表法分为咖啡因组与氨茶碱组各86例。比较两组早产儿用药前及用药后15、30min、1、1.5、2、4、6、12、12.5、24.5、36.5和48h血糖的变化。结果两组早产儿用药后除6、12和48h血糖值比较差异均无统计学意义（均P＞0.05），其他用药后时相比较差异均有统计学意义（均P＜0.05）。咖啡因组早产儿用药后30min血糖值上升，至1h达峰值，后逐渐回落；用药后30min、1、1.5、2及24.5h血糖值与用药前比较差异均有统计学意义（均P＜0.05）。氨茶碱组早产儿用药后血糖值上升，30min达峰值，后逐渐回落；用药后15、30min、1、1.5、2、4、6、12.5、24.5、36.5h血糖值与用药前比较差异均有统计学意义（均P＜0.05）。结论枸橼酸咖啡因可引起早产儿血糖升高，但升高幅度较氨茶碱小、持续时间也较短。     

Maximizing Breast Cancer Therapy with Awareness of Potential Treatment-Related Blood Disorders

In this review we summarize the impact of the various modalities of breast cancer therapy coupled with intrinsic patient factors on incidence of subsequent treatment-induced myelodysplasia and acute myelogenous leukemia (t-MDS/AML). It is clear that risk is increased for patients treated with radiation and chemotherapy at younger ages. Radiation is associated with modest risk, whereas chemotherapy, particularly the combination of an alkylating agent and an anthracycline, carries higher risk and radiation and chemotherapy combined increase the risk markedly. Recently, treatment with granulocyte colony-stimulating factor (G-CSF), but not pegylated G-CSF, has been identified as a factor associated with increased t-MDS/AML risk. Two newly identified associations may link homologous DNA repair gene deficiency and poly (ADP-ribose) polymerase inhibitor treatment to increased t-MDS/AML risk. When predisposing factors, such as young age, are combined with an increasing number of potentially leukemogenic treatments that may not confer large risk singly, the risk of t-MDS/AML appears to increase. Patient and treatment factors combine to form a biological cascade that can trigger a myelodysplastic event. Patients with breast cancer are often exposed to many of these risk factors in the course of their treatment, and triple-negative patients, who are often younger and/or BRCA positive, are often exposed to all of them. It is important going forward to identify effective therapies without these adverse associated effects and choose existing therapies that minimize the risk of t-MDS/AML without sacrificing therapeutic gain.

Implications for Practice

Breast cancer is far more curable than in the past but requires multimodality treatment. Great care must be taken to use the least leukemogenic treatment programs that do not sacrifice efficacy. Elimination of radiation and anthracycline/alkylating agent regimens will be helpful where possible, particularly in younger patients and possibly those with homologous repair deficiency (HRD). Use of colony-stimulating factors should be limited to those who truly require them for safe chemotherapy administration. Further study of a possible leukemogenic association with HRD and the various forms of colony-stimulating factors is badly needed.

     

鼻塞式同步间歇正压通气(NIPPV)联合布地奈德雾化治疗新生儿急性呼吸窘迫综合征疾病的临床应用研究

目的:分析鼻塞式同步间歇正压通气(NIPPV)联合布地奈德雾化治疗ARDS(新生儿急性呼吸窘迫综合征)疾病的临床应用效果。方法:纳入病例是2017年5月—2019年11月收治的104例ARDS新生儿,随机平均分为两组。参照组52例采纳CPAP(持续气道正压通气通气)治疗,实验组52例采纳NIPPV+布地奈德雾化治疗,对比两组呼吸机通气时间、用氧时间、住院时间、血气指标以及并发症发生情况。结果:实验组呼吸机通气时间、用氧时间、住院时间均明显短于参照组,差异有统计学意义P<0.05;实验组治疗3 d后PaCO2明显低于参照组,实验组治疗3 d后PH以及PaO2明显高于参照组,差异有统计学意义P<0.05;实验组并发症发生率(3.85%,2/52)明显低于参照组(21.15%,11/52),差异有统计学意义P<0.05。结论:NIPPV+布地奈德雾化可有效缩短ARDS患者机械通气时间,改善血气指标,降低并发症发生率,值得借鉴。     

Evodiamine-inspired dual inhibitors of histone deacetylase 1 (HDAC1) and topoisomerase 2 (TOP2) with potent antitumor activity

A great challenge in multi-targeting drug discovery is to identify drug-like lead compounds with therapeutic advantages over single target inhibitors and drug combinations. Inspired by our previous efforts in designing antitumor evodiamine derivatives, herein selective histone deacetylase 1 (HDAC1) and topoisomerase 2 (TOP2) dual inhibitors were successfully identified, which showed potent in vitro and in vivo antitumor potency. Particularly, compound 30a was orally active and possessed excellent in vivo antitumor activity in the HCT116 xenograft model (TGI = 75.2%, 150 mg/kg, p.o.) without significant toxicity, which was more potent than HDAC inhibitor vorinostat, TOP inhibitor evodiamine and their combination. Taken together, this study highlights the therapeutic advantages of evodiamine-based HDAC1/TOP2 dual inhibitors and provides valuable leads for the development of novel multi-targeting antitumor agents.     

Extracorporeal blood purification treatment options for COVID-19: The role of immunoadsorption

The activation of the innate and adaptive immune systems by SARS-CoV-2 causes the release of several inflammatory cytokines, including IL-6. The inflammatory hypercytokinemia causes immunopathological changes in the lungs including vascular leakage, and alveolar edema. As a result of these changes in the lungs, hypoxia and acute respiratory distress syndrome occur in patients with COVID-19. Even though there are clinical trials on the development of therapeutics and vaccines, there are currently no licensed vaccines or therapeutics for COVID-19. Pharmacological approaches have shown poor results in sepsis-like syndromes caused by the hypercytokinemia. Suppressing the cytokine storm is an important way to prevent the organ damage in patients with COVID-19. Extracorporeal blood purification could be proposed as an adjunctive therapy for sepsis, aiming to control the associated dysregulation of the immune system, which is known to protect organ functions. Several extracorporeal blood purification therapies are now available, and most of them target endotoxins and/or the cytokines and aim improving the immune response. For this purpose, plasmapheresis and immunoadsorption may be an important adjunctive treatment option to manage the complications caused by cytokine storm in critically ill patients with COVID-19.     

Ensayo clínico para determinar si el momento de administración del ácido tranexámico en la cirugía de prótesis total de rodilla con torniquete influye en el sangrado perioperatorio

Background and objectivesThe ideal timing of tranexamic acid administration in total knee arthroplasty with tourniquet remains unclear. Our primary objective was to prove if administering it before surgical incision, instead of before releasing the tourniquet, reduces postoperative bleeding. A second objective was to determine whether a second dose reduces post-operative bleeding.Material and methodsA prospective, double-blind clinical trial was performed on 212 patients scheduled for total knee arthroplasty. They were randomised into 4 groups. Tranexamic acid was administered before the surgical incision in “pre-induction groups” (1 and 2), and just before the tourniquet release in “pre-release groups” (3 and 4). Groups 2 and 4 received a second dose 3 hours post-surgery. Main outcome was postoperative bleeding (visible blood loss and calculated total bleeding). Secondary outcomes were haemoglobin variations, complications and transfusion rate.ResultsThe mean calculated total bleeding was 1563 ml (95%CI: 1445 to 1681) in preinduction groups versus 1576 ml (95%CI: 1439 to 1713) in pre-release groups (P = .9); 1579 ml (95%CI: 1452 to 1706) in single-dose groups versus 1559 ml (95%CI: 1431 to 1686) in double-dose groups (P = .82). One patient was transfused. The mean haemoglobin at discharge was 10.4 g/dl (95%CI: 10.2 to 10.7) in singledose groups versus 10.8 (95%CI: 10.6 to 11.1) in double-dose groups (P = .06).ConclusionsThere were no differences in bleeding or transfusion regarding the time of tranexamic acid administration. The second dose had not impact on outcomes.Trial registration: EudraCT 2016-000071-24.     

糖尿病患者腹部手术围手术期的处理

糖尿病已成为全球威胁人类健康的三大慢性非传染性疾病之一。需要外科手术的患者占所有糖尿病患者的25%,其围手术期病死率、并发症以及住院时间较正常人明显增加,因此对于糖尿病患者围手术期的处理方案显得尤为重要。但目前对于围手术期血糖控制范围仍众说纷纭,综合各研究结论,笔者认为将血糖控制在7.8~10 mmol/L是一个较为理想的范围。在患者术前、术中及术后应联合多学科制定各项相应的治疗方案,围手术期尤为注意避免患者发生低血糖和电解质紊乱的发生。也亟待后续大规模的随机对照试验进一步确定有效的血糖控制目标。