低分子肝素治疗脓毒症的前瞻性临床研究

目的 探讨低分子肝素对脓毒症的治疗作用。方法 40例脓毒症患者随机分为常规治疗组和 低分子肝素治疗组。观察两组患者治疗前后急性生理学与慢性健康状况Ⅱ(APACHEⅡ)评分、住重症监护治 疗病房(ICU)时间和28 d病死率差异,以及治疗前后白细胞介素-6(IL-6)、丙二醛(MDA)、超氧化物歧化酶 (SOD)、凝血功能和血小板计数(PLT)变化。结果 低分子肝素治疗组随治疗时间的延长,APACHEⅡ评分 和IL-6水平均下降,治疗后7 d与治疗前比较差异均有显著性(P均<0．05);而常规治疗组呈现先降后升 的趋势;治疗后7 d低分子肝素治疗组APACHE Ⅱ评分和IL-6水平均明显低于常规治疗组(P均<0．05)。 低分子肝素治疗组住ICU时间为(9．92±6．81)d,28 d病死率为40．9％,均低于常规治疗组(12．85±9．14)d 和50．0％,但差异无显著性。低分子肝素治疗组治疗后SOD明显升高[(159．13±99．31)kU／L比(318．38± 254．29)kU／L],MDA明显下降[(17．72±14．89)μmol／L比(6．62±5．53)μmol／L];常规治疗组则均呈相反 的变化趋势[SOD(180．99±169．40)kU／L比(135．16±107．73)kU／L;MDA(17．25±15．74)μmol／L比 (20．77±16．87)μmol／L];治疗后两组比较差异均有显著性(P均<0．05)。两组患者凝血酶原时间(PT)、白陶 土部分凝血酶原时间(KPTT)、纤维蛋白原(FIB)、PLT水平治疗前后差异均无显著性。结论 低分子肝素治 疗脓毒症可抑制炎性介质和氧自由基的释放,临床应用安全,无严重并发症。     

低分子肝素治疗脓毒症的临床研究

目的 探讨低分子肝素(low molecular weight heparin,LMWH)对脓毒症的治疗作用.方法 将北京大学人民医院急诊重症监护病房2006年1月至2007年6月收治的74例脓毒症患者分为低分子肝素(LMWH)治疗组49例及对照组(常规治疗组)25例.对照组早期用广谱抗生素,补充循环血容量,抑酸保护胃黏膜,纠正水、电解质及酸碱紊乱,营养支持及对症治疗.LMWH治疗组入院后给予低分子肝素钠0.4～0.6 ml(4000～6000 IU)皮下注射,每日2次,疗程一般为14 d(或用至患者出院或死亡,或有明显低凝状态或出血倾向);其他治疗同对照组.比较两组患者治疗前后急性生理学与慢性健康状况(acute physiology and chronic health evaluation,APACHE)Ⅱ评分、凝血指标、血小板计数的变化;比较两组出血并发症等情况;比较两组28 d转归及最终转归,并对两组患者进行生存分析.统计分析采用t检验、配对t检验、χ2检验,P＜0.05为差异有统计学意义.结果 LMWH治疗组住院28 d生存率为87.75%(43/49),对照组住院28 d生存率为64.00%(16/25),两组间比较χ2=5.780,治疗组明显高于对照组(P＜0.05),Kaplan-Meier生存分析也显示LMWH治疗组其生存率高于对照组(P＜0.05);治疗后7 dLMWH治疗组APACHE Ⅱ评分为(17.65±4.38)分,而对照组为(19.58±3.95)分,P=0.105,两组差异无统计学意义,但可看出LMWH治疗组的评分有所改善,其绝对值低于对照组,而LMWH治疗组治疗前与治疗后7 d比较(配对t检验),其P值为0.001,差异具有统计学意义.两组凝血指标(PT、PT活动度、APTT、FIB)及血小板水平治疗前后差异均无统计学意义(P＞0.05);与对照组相比,LMWH治疗组并未增加出血并发症的发生率(P＞0.05).结论 低分子肝素(LMWH)治疗可显著改善脓毒症患者的生存率,且无严重副作用,临床应用安全有效.     

抗凝血因子X a活性测定对低相对分子质量肝素治疗监测的观察

目的观察抗凝血因子(F)Xa活性测定,作为低相对分子质量肝素(LMWH)治疗的监测。方法用heptest试制盒对LMWH治疗的30例不稳定型心绞痛及30例用普通肝素(UFH)和30例用LMWH预防肾病综合征血栓形成倾向患者进行抗凝血因子(F)Xa活性、活化的部分凝血活酶时间(APTT)测定和血小板计数(Plt)。结果用LMWH治疗不稳定型心绞痛组,抗FXa测定在治疗第2天为(0.18±0.13),第10天为(0.30±0.19)u/ml。肾病组在治疗第2天为(0.21±0.15),第15天为(0.31±0.19),第30天为(0.37±0.14)u/ml。两组在治疗开始和结束检测抗FXa、APTT和Plt均无统计学的差异。LMWH抗FXa测定为(0.28±0.14)u/ml。结论虽然,抗FX     

Effects of macrophage polarization on gold nanoparticle-assisted plasmonic photothermal therapy

Tumor associated macrophages (TAM) are key pathogenic factors in neoplastic diseases. They are known to have plasticity and can polarize into two opposing phenotypes, including the tumoricidal M1 and the protumoral M2 phenotypes with high prevalence of M2-phentoypes in patients with poor prognosis. Strategies for targeting M2-TAM may consequently increase the efficacy of therapeutic strategies for cancer treatment. Gold nanorod-assisted plasmonic photothermal therapy (PPTT) has emerged as a promising treatment for cancer but the effects of macrophage polarization parameters in the performance of this new treatment modality is still unknown. Herein, human monocytic THP-1 cells were polarized into two opposite phenotypic macrophages (M1-TAM and M2-TAM) and their response to PPTT was examined. M2-TAM exhibits a three-fold increase in AuNP uptake compared to M1-TAM. Laser irradiation results in selective killing of pro-tumoral M2-TAM after treatment with AuNPs with limited effects on anti-tumoral M1-TAM. A positive correlation between the expression of CD206 marker and the AuNP uptake may indicate the role of CD206 in facilitating AuNP uptake. Our findings also suggest that the differences in AuNP avidity and uptake between the M1-TAM and M2-TAM phenotypes may be the rationale behind the effectiveness of PPTT in the treatment of solid tumors.

A preferential uptake of gold nanoparticles by macrophages with a protumoral M2 phenotype result in efficient killing upon laser irradiation while keeping M1 phenotypes relatively undamaged.     

Diagnosis and therapy of thrombophlebitis with special consideration of low molecular weight heparin

The clinical diagnosis of superficial thrombophlebitis is characterized by the occurrence of painful and inflamed cords along superficial veins and varices. Duplex sonography is recommended to rule out asymptomatic deep vein thrombosis which may be present in about 20% and to check potential sources of entrance of the thrombotic process into deep veins, like the junctions of great and small saphenous veins. Classic therapy is based on firm compression therapy and walking exercises. Incisions with expression of clots and anti-inflammatory drugs may reduce pain and inflammation. When phlebitis involves also the thigh and especially the proximal part of the great saphenous vein surgical ligation of the junction and local thrombectomy can be considered, preferably on an outpatient basis. Recent data from one randomised controlled trial demonstrate the efficacy of unfractionated heparin in a dose of 12,500 I.U. s. c. twice a day in this indication. According to another randomised controlled trial low molecular weight heparin (LMWH) may reduce the development of thromboembolic complications and also the relatively frequent extension of the thrombi in the superficial veins. Therapeutic doses seem to be more effective than prophylactic doses. While conventional therapy with compression and walking is sufficient for the majority of cases, the additional use of low molecular heparin is recommended in increased thromboembolic risk and when the thigh is involved. In the few studies available treatment time of 6-12 days is reported. More studies with special focus on indication, dosage and duration of therapy with LMWH are needed for the recommendation of clear therapeutic guidelines.     

A feasible strategy for self-assembly of gold nanoparticles via dithiol-PEG for photothermal therapy of cancers

We designed and explored self-assembled gold nanoparticles (SAGNPs) by introducing dithiol modified polyethylene glycol (PEG) for internanoparticle cross-linking. SAGNPs could enhance uptake into cancer cells and be disintegrated by glutathione (GSH) to achieve tumor microenvironment-activated biodegradation. This assembled structure improved the photothermal effect compared to single gold nanospheres.

We designed and explored self-assembled gold nanoparticles (SAGNPs) by introducing dithiol modified polyethylene glycol (PEG) for internanoparticle cross-linking.     

Effect of number density on optimal design of gold nanoshells for plasmonic photothermal therapy

Despite much research efforts being devoted to the design optimization of metallic nanoshells, no account is taken of the fact that the number of the nanoshells that can be delivered to a given cancerous site vary with their size. In this paper, we study the effect of the nanoshell number density on the absorption and scattering properties of a gold-nanoshell ensemble exposed to a broadband near-infrared radiation, and optimize the nanoshells’ dimensions for efficient cancer treatment by analyzing a wide range of human tissues. We first consider the general situation in which the number of the delivered nanoshells decreases with their mean radius R as ∝ R^−β, and demonstrate that the optimal design of nanoshells required to treat cancer most efficiently depends critically on β. In the case of β = 2, the maximal energy absorbed (scattered) by the ensemble is achieved for the same dimensions that maximize the absorption (scattering) efficiency of a single nanoshell. We thoroughly study this special case by the example of gold nanoshells with silica core. To ensure that minimal thermal injury is caused to the healthy tissue surrounding a cancerous site, we estimate the optimal dimensions that minimize scattering by the nanoshells for a desired value of the absorption efficiency. The comparison of gold nanoshells with different cores shows that hollow nanoshells exhibiting relatively low absorption efficiency are less harmful to the healthy tissue and, hence, are preferred over the strongly absorbing nanoshells. For each of the cases analyzed, we provide approximate analytical expressions for the optimal nanoshell dimensions, which may be used as design guidelines by experimentalists, in order to optimize the synthesis of gold nanoshells for treating different types of human cancer at their various growth stages.OCIS codes: (170.0170) Medical optics and biotechnology, (160.4236) Nanomaterials, (250.5403) Plasmonics, (350.5340) Photothermal effects     

低分子肝素对急性胰腺炎患者预后的改善作用

目的 观察低分子肝素抗凝治疗对急性胰腺炎患者预后的影响。方法 将41例急性胰腺炎患者随机分为抗凝治疗组(17例)和常规治疗对照组(24例)。抗凝治疗组给予低分子肝素钠40 mg或低分子肝素钙0.01 ml／kg皮下注射,12 h 1次;其他治疗同常规治疗对照组。观察两组患者的血清酶学及预后。结果低分子肝素抗凝治疗能明显改善急性胰腺炎患者的血象及动脉血氧分压变化,缩短住院时间,并能在一定程度上降低急性水肿型胰腺炎的重症化率,减少其二次手术率,降低病死率。低分子肝素抗凝治疗并没有加重急性胰腺炎的出血倾向或出血并发症。结论 低分子肝素抗凝治疗对急性胰腺炎是安全、有效的,能明显改善急性胰腺炎患者的预后。     

Improved low molecular weight Myc-Max inhibitors

Compounds that selectively prevent or disrupt the association between the c-Myc oncoprotein and its obligate heterodimeric partner Max (Myc-Max compounds) have been identified previously by high-throughput screening of chemical libraries. Although these agents specifically inhibit the growth of c-Myc-expressing cells, their clinical applicability is limited by their low potency. We describe here several chemical modifications of one of these original compounds, 10058-F4, which result in significant improvements in efficacy. Compared with the parent structure, these analogues show enhanced growth inhibition of c-Myc-expressing cells in a manner that generally correlates with their ability to disrupt c-Myc-Max association and DNA binding. Furthermore, we show by use of a sensitive fluorescence polarization assay that both 10058-F4 and its active analogues bind specifically to monomeric c-Myc. These studies show that improved Myc-Max compounds can be generated by a directed approach involving deliberate modification of an index compound. They further show that the compounds specifically target c-Myc, which exists in a dynamic and relatively unstructured state with only partial and transient alpha-helical content.     

Gut microbiota modulation and gold nanoparticle‐mediated photothermal therapy for treatment of recalcitrant acne

Recent studies highlight that gut dysbiosis, an imbalanced state of intestinal microbiota, exacerbates skin inflammation. Here, we showed the presence of gut microbiota alterations in two patients with recalcitrant acne and investigated the impact of its therapeutic modulation together with gold nanoshell‐mediated photothermal therapy (gold PTT).     

低分子肝素治疗脓毒症中P-选择素的变化及临床意义研究

目的 研究低分子肝素治疗脓毒症过程中P-选择素(CD62p)表达的动态变化及其临床意义.方法 20例健康体检者为正常组.将40例脓毒症患者随机分为对照组和抗凝组,在诊断脓毒症第1、3、5、7天,采用ELISA法检测CD62p表达,同时观察急性生理和慢性健康状况评分Ⅱ(APACHEⅡ)及血浆凝血酶原时间(PT)、活化部分凝血活酶时间(APTT)、纤维蛋白原(FIB)、血小板(PLT)和D-二聚体(D-D)的变化,并统计多器官功能障碍综合征(MODS)发生率及28 d病死率.结果 与正常组比较,对照组CD62p表达显著增加(P均<0.05).随着时间的延长,抗凝组CD62p表达及APACHEⅡ评分均下降,治疗第5、7天与治疗第1天比较差异有统计学意义(P均<0.05);而对照组两指标是先下降后升高.治疗第7天抗凝组CD62p表达及APACHEⅡ评分均低于对照组(P均<0.05).抗凝组MODS发生率(20%)较对照组降低(50%,P<0.05);28 d病死率(20%)也较对照组(35%)降低,但差异无统计学意义(P>0.05).对照组和抗凝组治疗前后PT、APTT、FIB、PLT和D-D水平比较差异均无统计学意义(P均>0.05).抗凝组CD62p表达与APACHEⅡ评分呈正相关(r=0.989,P=0.011).结论 脓毒症早期血小板就处于高激活状态,且活化程度与疾病严重程度呈正相关;早期应用低分子肝素治疗脓毒症,可显著抑制CD62p表达,降低MODS发生率,改善预后,且临床应用安全.     

Folate receptor-targeting mesoporous silica-coated gold nanorod nanoparticles for the synergistic photothermal therapy and chemotherapy of rheumatoid arthritis

The synergy of photothermal therapy (PTT) and chemotherapy is widely regarded as an effective treatment for complex diseases, such as cancer and inflammation. In this paper, we report the synthesis of a nanoscaled drug delivery system, which was composed of a gold nanorod (GNR) as the photothermal agent and a mesoporous silica shell as the methotrexate (MTX) reservoir, named FAGMs. Due to folate modification on the surface, FAGMs targeted specifically activated macrophages in rheumatoid arthritis (RA). Under 808 nm laser irradiation, FAGMs could kill macrophages by reaching sufficient local hyperthermia with excellent efficiency in the photothermal conversion of GNRs. Meanwhile, internal heating caused hydrogen bond fracture; thus, MTX released rapidly from FAGMs for localized synergistic PTT and chemotherapy. The FAGMs had a mean particle size of about 180 nm and a zeta potential of 14.36 mV. The release rate of MTX from FAGMs in vitro increased markedly under 808 nm laser irradiation. In a cellular uptake study, stronger fluorescence signals were observed in activated macrophages when treated with FAGMs, suggesting that folic acid molecules enabled the enhancement of endocytosis into activated macrophages. In rats with adjuvant-induced arthritis, synergistic treatment excellently inhibited the progression of RA. These results demonstrated that FAGMs could be promising for the treatment of RA.

The use of targeted nanoparticles MTX-FAGMs in combined NIR-induced PTT and traditional chemotherapy has potential as a desirable nanopharmaceuticals platform for the treatment of RA.     

Pharmacology of low molecular weight heparins.

Although intravenous heparin has been the treatment of choice for acute VTE disease, LMWHs are gaining wider recognition and support as not only a new option but also as the standard of care. Each LMWH is viewed as a unique drug by regulatory agencies because of their differing physical and pharmacokinetic attributes. LMWHs have high absorption, high bioavailability, and long half-lives enabling once- or twice-daily dosing with predictable dose-response relationships. These factors enable the LMWHs to be used without laboratory monitoring and at home for acute DVT management. Studies continue to show that LMWH preparations are as at least as effective as heparin in a variety of settings, including VTE disease prophylaxis, management of acute VTE disease, unstable angina, and NSTEMI. They are at least as safe as heparin relative to hemorrhagic complications. Heparin-induced thrombocytopenia is less of a problem with LMWHs. Use of LMWHs has resulted in cost benefits in the treatment of acute DVT, unstable angina, and NSTEMI as well as in prophylaxis against venous thromboembolism. Emergency physicians, because of their unique position at the forefront of acute care, will soon regularly use LMWHs.     

低分子肝素皮下注射操作的最佳证据总结

目的 检索、评价和整合低分子肝素皮下注射操作的相关证据。方法 计算机检索国内外数据库、相关专业网站中关于低分子肝素皮下注射操作的临床决策、推荐实践、证据总结、技术报告、指南、专家共识、系统评价,文献检索时限为建库至2021年11月,由2名研究者独立进行文献质量评价后,根据主题对证据进行提取与汇总。结果 根据纳入标准,共筛选出9篇文献,包括2篇证据总结、2篇专家共识、5篇系统评价。通过文献阅读、证据提取和归类,从注射前准备、注射中规范、注射后处置3个方面总结出12条证据。结论 该研究总结了低分子肝素皮下注射操作的最佳证据,可为护理人员开展临床实践提供参考。护理人员应结合临床情境、患者意愿,审慎地选择并应用证据,从而保障注射安全,降低相关并发症的发生率。