Establishment of an Evaluation Method for Gene Silencing by Serial Pulmonary Administration of siRNA and pDNA Powders: Naked siRNA Inhalation Powder Suppresses Luciferase Gene Expression in the Lung

In order to evaluate the in vivo effect of inhaled formulations, it is a gold standard to create a lung metastasis model by intravenously injecting cancer cells into an animal. Because the cancer grows from the blood vessel side, there is a possibility of underestimating the effect of an inhaled formulation administered to the lung epithelium side. In addition, the metastasis model has disadvantages in terms of preparation time and expense. The present study aimed to establish a new method to evaluate the effect of an inhaled small interfering RNA (siRNA) formulation that is more correct, more rapid, and less expensive. We investigated whether siRNA can suppress gene expression of plasmid DNA (pDNA) by serial pulmonary administration of siRNA and pDNA powders prepared by spray-freeze-drying. We revealed that formulations of dry siRNA powder significantly suppressed gene expression of pDNA powder compared with a control group with no siRNA. Naked siRNA inhalation powder with no vector showed the suppression of gene expression equivalent to that of an siRNA-polyethyleneimine complex without damaging tissues. These results show that the present method is suitable for evaluating the gene-silencing effect of inhaled siRNA powders.     

宫腔内灌注粒细胞集落刺激因子联合低分子肝素在薄型子宫内膜患者冻融胚胎移植周期中的研究

目的:探讨宫腔内灌注粒细胞集落刺激因子(G-CSF)联合低分子肝素(LMWH)对薄型子宫内膜患者冻融胚胎移植(FET)周期中的临床疗效。方法:选取2018年6月-2019年10月于山西医科大学第一医院进行FET助孕治疗的薄型子宫内膜患者175例,根据患者自身意愿分为3组,A组:63例患者仅接受激素替代治疗;B组:52例患者接受激素替代治疗+宫腔内G-CSF灌注;C组:60例患者接受激素替代治疗+宫腔内G-CSF灌注+皮下注射LMWH。对3组患者的子宫内膜厚度、子宫内膜血流阻力指数(RI)、搏动指数(PI)、周期取消率、胚胎种植率、临床妊娠率、早期流产率、异位妊娠率等指标进行比较。结果:在内膜转化日,与A组相比,B、C组子宫内膜厚度、Ⅱ+Ⅲ型血流比例均增加,RI、PI均降低(P<0.05)。治疗结局方面,与A组相比,B、C组胚胎种植率、临床妊娠率增加,周期取消率降低,差异有统计学意义(P<0.05);B、C组间比较差异无统计学意义(P>0.05);C组早期流产率较B组降低,差异有统计学意义(P<0.05)。结论:在FET周期中宫腔内灌注G-CSF可提高薄型子宫内膜患者的子宫内膜厚度,改善子宫内膜的血流情况,提高胚胎种植率及临床妊娠率,注射LMWH可降低早期流产率。     

Comparison of fondaparinux sodium and low molecular weight heparin in the treatment of hypercoagulability secondary to traumatic infection

Purpose: To compare the effects and side-effects of fondaparinux sodium and low molecular weight heparin in patients with hypercoagulability accompanied with traumatic infection. Methods: Thirty-six patients with post-traumatic infections in our hospital intensive care center were diagnosed with hypercoagulability from February 2012 to February 2013. These patients were randomly divided into 2 groups. In group F (18 patients), the patients were treated with fondaparinux sodium, 2.5 mg, 1/d for 11 d. In group L (18 patients), the patients were treated with low molecular weight heparin, 4100 U, 1/12 h for 11 d. The incidence of deep vein thrombosis, bleeding events and multiple organ dysfunction syndrome (MODS) and mortality of two groups after anticoagulation therapy were analyzed. Fibrinogen, D-dimer level and activity of antithrombin III were measured by the coagulation analyzer. Results: The incidence of deep vein thrombosis, MODS incidence and mortality were not significantly different between the two groups. The rate of bleeding evens in group F was lower than group L (p < 0.05). Antithrombin III got an upward trend after anticoagulant therapy, in which it was higher in group F than in group L on the 5th d and 11th d (p<0.05). Fibrinogen levels were gradually increased, and there was no significant difference between two groups (p>0.05). D-dimer was significantly decreased after anticoagulant therapy for 5 d (p<0.01), and there were significant differences between two groups on the 5th d and 7th d (p < 0.05). It showed no significant difference on the 11th d (p>0.05). Conclusion: Fondaparinux sodium and low molecular weight heparin can effectively improve coagulopathy in patients with traumatic infection. Compared with low molecular weight heparin, fondaparinux sodium may reduce the risk of bleeding events in patients with hypercoagulability accompanied by traumatic infection.     

老年人高龋患者牙菌斑中变形链球菌临床分离株合成胞外多糖能力的研究

目的；探讨老年人高龋患者牙菌斑中变形链球菌（血清C型）临床分离株合成胞外多糖能力。方法：收集老年人高龋患者、无龋者牙菌斑中变形链球菌（血清C型），检测合成胞外多糖能力，并与国际参考菌株比较。结果：老年人高龋患者牙菌斑中分离出的变形链球菌临床分离株合成胞外多糖能力明显高于无龋组。同时研究发现，在老年人高龋患者同一个体牙菌斑中，不同基因型变形链球菌临床分离株合成胞外多糖的能力仔任差异，在无龋者牙菌斑中发现没有这一现象。结论：老年人高龋患者牙菌斑中变形链球菌（血清C型）临床分离株合成胞外多糖能力强的菌株与龋病的发生密切有关。     

Low Rate of Intrahospital Deep Venous Thrombosis in Acutely Ill Medical Patients: Results From the AURELIO Study

Objective

To evaluate the effect of hospitalization on deep venous thrombosis (DVT) rate by the cumulative incidence of DVT in the proximal venous tract of the lower limbs at admission and discharge.

A pilot study of central venous catheter survival in cancer patients using low-molecular-weight heparin (dalteparin) and warfarin without catheter removal for the treatment of upper extremity deep vein thrombosis (The Catheter Study)

BACKGROUND: Central venous catheters in patients with cancer are associated with development of deep vein thrombosis (DVT); however, there is no accepted standard treatment. OBJECTIVES: To assess the safety and effectiveness of a management strategy for central venous catheter-related DVT in cancer patients consisting of dalteparin and warfarin without the need for line removal. PATIENTS/METHODS: Patients older than 18 years of age with an active malignancy and who had symptomatic, acute, objectively documented UEDVT were eligible. Patients were treated with dalteparin 200 IU kg(-1) per day for 5-7 days and warfarin with a target International Normalized Ratio of 2.0-3.0. Patients were followed for 3 months for recurrent venous thromboembolism, major hemorrhage and survival of the central venous catheter. RESULTS: There were 74 patients (48 males). The average age was 58 years. There were no episodes of recurrent venous thromboembolism and three (4%) major bleeds. No lines were removed because of infusion failure or recurrence/extension of DVT. CONCLUSION: Treatment of UEDVTs secondary to central catheters in cancer patients with standard dalteparin/warfarin can allow the central line to remain in situ with little risk of line failure or recurrence/extension of the DVT.     

Regional anaesthesia in patients taking anticoagulant drugs

Many surgical patients are taking drugs that impair normal coagulation, and this causes concern about the risk of perioperative bleeding events. The anaesthetist is particularly concerned about compressive vertebral canal haematomas, which may occur after spinal or epidural anaesthetic techniques. Fortunately, the risk of this complication is very low. The major risk factors are coagulopathy or technical difficulties with the block. There is also concern about perineural haematomas, which may be associated with peripheral nerve blocks. This article attempts to put the risks of these complications into context, with reference to different classes of anticoagulant drugs.     

骨科大手术中的静脉血栓的预防:口服抗凝药的系统回顾和间接比较

目的:基于有效的循证证据,以低分子肝素为对照组,分析达比加群、阿哌沙班和利伐沙班在骨科大手术后预防静脉血栓的有效性与安全性。方法:在Pub Med和Embase中系统地检索随机对照试验以及参考文献中关键的文章,这些文章评价了以低分子肝素为对照组,达比加群、阿哌沙班和利伐沙班在进行了骨科大手术的病人中的作用。结果:评价的结果包括总静脉血栓(total VTE)、深静脉血栓(DVT)、肺栓塞(PE)、死亡和主要出血事件(major bleeding)。笔者独立地评价了每1篇文章的方法质量同时独立地提取了文献数据。在总静脉血栓预防方面,利伐沙班和阿哌沙班优于达比加群,分别为[RR=0.37,95%CI(0.23,0.60)]和[RR=0.58,95%CI(0.35,0.96)]。利伐沙班和阿哌沙班之间没有区别[RR=0.64,95%CI(0.33,1.25)]。利伐沙班与阿哌沙班相比增加了出血风险[RR=1.57,95%CI(1.20,2.07)],利伐沙班与达比加群相比增加了出血风险[RR=1.25,95%CI(0.93,1.70)]。阿哌沙班和达比加群在出血方面没有差别[RR=0.78,95%CI(0.58,1.07)]。结论:在接受骨科大手术病人之中,利伐沙班和阿哌沙班2种药物与达比加群相比,预防静脉血栓的效果更好,出血风险相似。利伐沙班与阿哌沙班相比,预防静脉血栓的效果相似,但是增加了出血的风险。     

Low-Molecular-Weight Heparin or Dual Antiplatelet Therapy Is More Effective Than Aspirin Alone in Preventing Early Neurological Deterioration and Improving the 6-Month Outcome in Ischemic Stroke Patients

Background and Purpose

Dual antiplatelet therapy (DAT) with clopidogrel and aspirin has been shown to confer greater protection against early neurological deterioration (END) and early recurrent ischemic stroke (ERIS) than aspirin alone in patients who have experienced an acute ischemic stroke. However, few studies have compared the effects of anticoagulation therapy with low-molecular-weight heparin (LMWH), DAT, and aspirin.

Methods

Patients with acute ischemic stroke (n=1,467) were randomized to therapy groups receiving aspirin (200 mg daily for 14 days, followed by 100 mg daily for 6 months), DAT (200 mg of aspirin and 75 mg of clopidogrel daily for 14 days, then 100 mg of aspirin daily for 6 months), or LMWH (4,000 antifactor Xa IU of enoxaparin in 0.4 mL subcutaneously twice daily for 14 days, followed by 100 mg of aspirin daily for 6 months). The effects of these treatment strategies on the incidence of END, ERIS, and deep-vein thrombosis (DVT) were observed for 10-14 days after treatment, and their impacts on a good outcome were evaluated at 6 months.

Results

The DAT and LMWH were associated with a more significant reduction of END and ERIS within 14 days compared with aspirin-alone therapy. In addition, LMWH was associated with a significantly lower incidence of DVT within 14 days. At 6 months, DAT or LMWH improved the outcome among patients aged >70 years and those with symptomatic stenosis in the posterior circulation or basilar artery compared with aspirin.

Conclusions

LMWH or DAT may be more effective than aspirin alone for reducing the incidence of END and ERIS within 14 days, and is associated with improved outcomes in elderly patients and those with stenosis in the posterior circulation or basilar artery at 6 months poststroke.     

低分子肝素对慢性阻塞性肺疾病急性加重期疗效初探

目的:分子肝素在慢性阻塞性肺疾病急性加重期(AECOPD)抗凝治疗中的应用价值。方法:将92例AECOPD患者随机分成对照组和治疗组,每组各46例。治疗组患者在对照组常规治疗基础上予低分子肝素4 000 U皮下注射,每天2次,治疗7 d。观察治疗前后患者肺功能指标FEV1及FEV1/FVC%,血气分析指标Pa O2、Pa CO2,血超敏C-反应蛋白(hs-CRP)和血D-二聚体水平的变化情况。结果:两组FEV1、FEV1/FVC%、Pa O2、Pa CO2、hs-CRP和血D-二聚体水平治疗前后比较,治疗组优于对照组(P<0.05)。结论:低分子肝素治疗AECOPD效果明显。