Low-molecular-weight heparin and preeclampsia—does the sword cut both ways?Three case reports and review of literature

BACKGROUND Low-molecular-weight heparins(LMWH)are the most commonly used anticoagulants during pregnancy.It is considered to be the drug of choice due to its safety in not crossing placenta.Considering the beneficial effect in the improvement of microcirculation,prophylactic application of LMWH in patients with preeclampsia became a trend.However,the bleeding risk related with LMWH in preeclampsia patients has seldomly been evaluated.This current study aimed to identify the potential risks regarding LMWH application in patients with preeclampsia.CASE SUMMARY Herein we present a case series of three pregnant women diagnosed with preeclampsia on LMWH therapy during pregnancy.All the cases experienced catastrophic hemorrhagic events.After reviewing the twenty-one meta-analyses,the bleeding risk related with LMWH seems ignorable.Only one study analyzed the bleeding risk of LMWH and found a significantly higher risk of developing PPH in women receiving LMWH.Other studies reported minor bleeding risks,none of these were serious enough to stop LMWH treatment.Possibilities of bleeding either from uterus or from intrabdominal organs in preeclampsia patients on LMWH therapy should not be ignored.Intensive management of blood pressure even after delivery and homeostasis suture in surgery are crucial.CONCLUSION Consideration should be given to the balance between benefits and risks of LMWH in patients with preeclampsia.

Heparin is an effective treatment for preventing liver failure after hepatectomy

BACKGROUND Posthepatectomy liver failure(PHLF)is one of the most important causes of death following liver resection.Heparin,an established anticoagulant,can protect liver function through a number of mechanisms,and thus,prevent liver failure.AIM To look at the safety and efficacy of heparin in preventing hepatic dysfunction after hepatectomy.METHODS The data was extracted from Multiparameter Intelligent Monitoring in Intensive Care III(MIMIC-III)v1.4 pinpointed patients who had undergone hepatectomy for liver cancer,subdividing them into two cohorts:Those who were injected with heparin and those who were not.The statistical evaluations used were unpaired ttests,Mann-Whitney U tests,chi-square tests,and Fisher’s exact tests to assess the effect of heparin administration on PHLF,duration of intensive care unit(ICU)stay,need for mechanical ventilation,use of continuous renal replacement therapy(CRRT),incidence of hypoxemia,development of acute kidney injury,and ICU mortality.Logistic regression was utilized to analyze the factors related to PHLF,with propensity score matching(PSM)aiming to balance the preoperative disparities between the two groups.RESULTS In this study,1388 patients who underwent liver cancer hepatectomy were analyzed.PSM yielded 213 matched pairs from the heparin-treated and control groups.Initial univariate analyses indicated that heparin potentially reduces the risk of PHLF in both matched and unmatched samples.Further analysis in the matched cohorts confirmed a significant association,with heparin reducing the risk of PHLF(odds ratio:0.518;95%confidence interval:0.295-0.910;P=0.022).Additionally,heparin treatment correlated with improved short-term postoperative outcomes such as reduced ICU stay durations,diminished requirements for respiratory support and CRRT,and lower incidences of hypoxemia and ICU mortality.CONCLUSION Liver failure is an important hazard following hepatic surgery.During ICU care heparin administration has been proved to decrease the occurrence of hepatectomy induced liver failure.This indicates that heparin may provide a hopeful option for controlling PHLF.

Application of aspirin and low molecular weight heparin in major orthopedic surgery:Meta analysis of a randomized controlled trial

Objective:The perioperative period of major orthopedic surgery is associated with a high risk of thrombosis,but the best chemopreventive agent for thrombosis prophylaxis is still inconclusive.For this reason,this paper evaluated the efficacy and safety of aspirin versus low-molecular heparin using a Meta-analysis.Methods:Ten randomized controlled studies on the application of aspirin and low-molecular heparin for the prevention of deep vein thrombosis in orthopedic major surgery were retrieved by computer searches of PubMed,CochraneLibrary,WebofScience,China Knowledge Network,Wanfang,and Vipul databases according to inclusion and exclusion criteria,and the literature was managed using Endnote software,and the data were analyzed using Revman 5.3 software was used to perform Meta-analysis of the extracted data,focusing on the effects of these two drugs on pulmonary embolism,deep vein thrombosis,major bleeding events,minor bleeding events,wound complications,mortality and blood loss within 90 days after major orthopedic surgery.Results:(1)Ten randomized controlled trials of high quality were included,with a total of 12,974 patients,7,026 in the aspirin group and 5,948 in the low-molecular heparin group;(2)Meta-analysis showed that aspirin had a higher incidence of pulmonary embolism(OR=1.59,95%CI:1.02 to 2.49,P=0.04)and deep vein thrombosis(OR=1.60,95%CI:1.26 to 2.02,P=0.0001)than low molecular heparin;(3)The incidence of major bleeding events(OR=0.85,95%CI:0.47 to 1.55,P=0.60),minor bleeding events(OR=0.79,95%CI:0.55 to 1.12,P=0.18),adverse wound reactions(OR=0.79,95%CI:0.48 to 1.31,P=0.36),mortality within 90 days(OR=0.69,95%CI:0.20 to 2.31,P=0.55)and perioperative blood loss(MD=0.69,95%CI:0.20 to 2.31,P=0.55)in both drug groups,mortality within 90 days(OR=0.69,95%CI:0.20 to 2.31,P=0.55)and perioperative blood loss(MD=0.69,95%CI:0.20 to 2.31,P=0.55)were not statistically significant.Conclusion:Low-molecular heparin was superior to aspirin in the prevention of pulmonary embolism and lower extremity deep vein thrombosis after major orthopedic surgery,but the safety and adverse drug reactions of both groups were basically similar.Based on this,the authors recommend that low-molecular heparin should be preferred for the prevention of deep vein thrombosis in major orthopaedic surgery;however,the inclusion of randomized controlled trials remains limited,necessitating high-quality,large-sample,long-term follow-up clinical studies.

甘草甜素对喉癌Hep-2细胞侵袭和迁移的影响及机制研究

目的:探究甘草甜素(Gly)对喉癌Hep-2细胞侵袭和迁移的影响及作用机制。方法:体外培养正常人喉黏膜上皮细胞和喉癌Hep-2细胞,实时荧光定量PCR(RT-qPCR)法和蛋白印迹实验检测微小RNA-205-5p(miR-205-5p)、沉默信息调节因子2相关酶3(SIRT3)mRNA和蛋白表达水平。将喉癌Hep-2细胞分为对照组、Gly低浓度组、Gly中浓度组、Gly高浓度组、Gly高浓度+空载质粒组、Gly高浓度+miR-205-5p抑制剂组。各组给予相应浓度的Gly干预或转染对应质粒培养48 h。Transwell实验和划痕实验分别检测各组Hep-2细胞侵袭和迁移能力。RT-qPCR法和蛋白印迹实验检测各组Hep-2细胞miR-205-5p、SIRT3 mRNA和蛋白表达水平。双荧光素酶报告基因实验分析miR-205-5p与SIRT3的靶向关系。结果:与人喉黏膜上皮细胞比较,喉癌Hep-2细胞miR-205-5p水平降低,SIRT3 mRNA和蛋白水平升高(均P<0.05)。与对照组比较,Gly低、中、高浓度组穿膜细胞数和划痕愈合率、SIRT3 mRNA和蛋白水平依次降低,miR-205-5p水平依次升高(均P<0.05)。与Gly高浓度组和Gly高浓度+空载质粒组比较,Gly高浓度+miR-205-5p抑制剂组穿膜细胞数和划痕愈合率、SIRT3 mRNA和蛋白水平升高,miR-205-5p水平降低(均P<0.05)。miR-205-5p可靶向调控SIRT3表达。结论:Gly能够抑制Hep-2细胞侵袭和迁移,其机制可能与上调miR-205-5p表达,进而靶向下调SIRT3表达有关。

Anti-infection effects of heparin on SARS-CoV-2 in a diabetic mouse model

Severe acute respiratory syndrome coronavirus 2(SARSCo V-2)infection can result in more severe syndromes and poorer outcomes in patients with diabetes and obesity.However,the precise mechanisms responsible for the combined impact of coronavirus disease 2019(COVID-19)and diabetes have not yet been elucidated,and effective treatment options for SARS-Co V-2-infected diabetic patients remain limited.To investigate the disease pathogenesis,K18-h ACE2 transgenic(h ACE2^(Tg))mice with a leptin receptor deficiency(h ACE2-Lepr^(-/-))and high-fat diet(h ACE2-HFD)background were generated.The two mouse models were intranasally infected with a 5×10^(5) median tissue culture infectious dose(TCID_(50))of SARSCo V-2,with serum and lung tissue samples collected at 3days post-infection.The h ACE2-Lepr^(-/-)mice were then administered a combination of low-molecular-weight heparin(LMWH)(1 mg/kg or 5 mg/kg)and insulin via subcutaneous injection prior to intranasal infection with1×10^(4) TCID_(50)of SARS-Co V-2.Daily drug administration continued until the euthanasia of the mice.Analyses of viral RNA loads,histopathological changes in lung tissue,and inflammation factors were conducted.Results demonstrated similar SARS-Co V-2 susceptibility in h ACE2^(Tg)mice under both lean(chow diet)and obese(HFD)conditions.However,compared to the h ACE2-Lepr^(+/+)mice,h ACE2-Lepr^(-/-)mice exhibited more severe lung injury,enhanced expression of inflammatory cytokines and hypoxia-inducible factor-1α(HIF-1α),and increased apoptosis.Moreover,combined LMWH and insulin treatment effectively reduced disease progression and severity,attenuated lung pathological changes,and mitigated inflammatory responses.In conclusion,preexisting diabetes can lead to more severe lung damage upon SARS-Co V-2 infection,and LMWH may be a valuable therapeutic approach for managing COVID-19patients with diabetes.

HEPS增强器凸轨磁铁脉冲电源的设计与实现

高能同步辐射光源(HEPS)是国内首台第四代同步辐射光源,包括一个储存环、一个增强器以及一个直线加速器。作为典型的低发射度储存环(LER),其动力学孔径远小于物理孔径,对此选择了一种新颖的在轴置换注入方案。其中,增强器负责实现束流从500 MeV到6 GeV的升能。为了降低增强器引出冲击磁铁的冲击强度,在引出环节之前使用4台凸轨磁铁来辅助冲击磁铁完成这一动作。凸轨磁铁磁场波形要求底宽小于1 ms的半正弦波。根据仿真以及测试结果,采用绝缘栅双极型晶体管(IGBT)串联快恢复二极管的经典LC谐振电路拓扑。此外,设计了能量回收支路,来降低电容在充电过程中功率损耗以及对输出脉冲电流波形的影响。目前,已完成脉冲电源样机的研制与测试,各项结果表明,该脉冲电源能够满足高能光源增强器高能引出系统的各项要求。

Delayed Onset Low Molecular Weight Heparin Induced Skin Necrosis on a Hemodialysis Patient

Delayed onset low molecular weight heparin induced skin necrosis is a rare adverse event. It usually occurs at the site of injection, and typically develops within 2 weeks of starting therapy. However, in our case, we presented a 62-year-old woman who is on Hemodialysis twice a week. Her hemodialysis prescription included Enoxaparine 0.2 cc IV as anticoagulant. On her third month of regular hemodialysis, she developed skin necrosis on her right leg and left hand. The diagnosis was made clinically and by exclusion of other possible causes of skin necrosis in a chronic kidney disease patient, such as calciphylaxis. The most important aspect of management, in this case, is early recognition and withdrawal of its use, which were done in our patient.

双硫仑联合二价铜离子诱导铜死亡抑制肝癌细胞Hep3B增殖、迁移和侵袭

目的探讨双硫仑(disulfiram,DSF)联合二价铜离子(Cu^(2+))对肝癌细胞增殖、迁移和侵袭的影响及其作用机制。方法体外培养肝癌Hep3B细胞,分别采用DSF(30 nmol/L)溶液、Cu^(2+)(1μmol/L)溶液和铜螯合剂四硫代钼酸铵(ammonium tetrathiomolybdateⅥ,ATTM)(30 nmol/L)溶液单独或联合干预,以二甲基亚砜(dimethyl sulfoxide,DMSO)(30 nmol/L)作用的细胞为对照组。分别采用CCK-8实验、划痕实验和Transwell小室实验检测细胞的增殖能力、迁移能力和侵袭能力;采用免疫荧光实验检测细胞中铜死亡相关蛋白二氢硫辛酰胺-S-乙酰转移酶(dihydrolipoamide S-acetyltransferase,DLAT)和铁氧还蛋白1(ferredoxin 1,FDX1)的表达。结果与对照组相比,DSF、Cu^(2+)单独或联合干预后Hep3B细胞的增殖、迁移和侵袭能力均下降(均P<0.05),其中DSF+Cu^(2+)联合干预的细胞增殖、迁移和侵袭能力下降更加显著(均P<0.0001)。在DSF联合Cu^(2+)的基础上加入ATTM后逆转了DSF联合Cu^(2+)对Hep3B细胞增殖、迁移和侵袭的抑制作用,其增殖、迁移以及侵袭能力较DSF+Cu^(2+)组增强(均P<0.05)。与对照组相比,DSF、Cu^(2+)单独干预后铜死亡相关蛋白DLAT和FDX1的荧光强度改变并不明显,但Cu^(2+)联合DSF后DLAT蛋白的荧光强度增加而FDX1蛋白的荧光强度减弱,加入ATTM后则逆转了DLAT和FDX1蛋白的表达趋势。结论DSF联合Cu^(2+)能抑制肝癌细胞Hep3B增殖、迁移和侵袭能力,其作用机制可能是通过诱导铜死亡的发生实现。

Rivaroxaban for the treatment of heparin-induced thrombocytopenia with thrombosis in a patient undergoing artificial hip arthroplasty:A case report

BACKGROUND Anticoagulation treatment after lower limb surgery is one of the key methods to avoid thrombosis,and low-molecular-weight heparin is the treatment that is most frequently used in clinical practice.But one uncommon side effect of lowmolecular-weight heparin is heparin-induced thrombocytopenia(HIT),which can develop into thrombosis if not caught early or managed incorrectly.CASE SUMMARY We present a case of a patient who underwent hip arthroplasty and experienced thrombocytopenia due to HIT on the 9th d following the application of lowmolecular-weight heparin anticoagulation.We did not diagnose HIT in time and applied 1 unit of platelets to the patient,which led to thrombosis.Luckily,the patient recovered following effective and timely surgery and treatment with rivaroxaban.CONCLUSION Patients using low-molecular-weight heparin after lower limb surgery need to have their platelet counts regularly checked.If HIT develops,platelet treatment should be given with caution.

Effect of heparin on recurrent IVF-ET failure patients

Objective:To elucidate the possible role of unfractionated heparin in patients with failed repeated in in vitro fertilization and embryo transfer(IVF-ET)and thrombophilia.Methods:This case control study evaluated the efficacy of the unfractionated heparin in increasing the pregnancy and implantation ratio in women with recurrent IVF-ET failures.Eighty-six women received in vitro fertilization/intracytoplasmic sperm injection(IVF/ICSI)with a record of three or more previous IVF-ET failures.Participants were randomly distributed into two groups.Group A(n=43)received unfractionated heparin 5000 IU twice daily,and group B(n=43)did not take any antithrombotic drugs.Coagulation abnormalities such as factor桋Leiden(FVL)mutation,methylene tetra hydro folate reductase(MTHFR)mutation and prothrombin mutation(F栻)were evaluated.Age,body mass index,basal follicular stimulating hormone,basal estradiol,duration of infertility,and number of IVF-ET failures were compared between two groups.Results:45.0%and 17.4%of women were pregnant with and without MTHFR and prothrombin mutation,respectively,when they received unfractionated heparin treatment.The implantation rate was more in group A(12.5%)than group B(4.3%)and differences in the fertilization rate of the two groups were observed(27.7%vs.35.9%).The clinical pregnancy rate per cycle was remarkably more in group A(30.2%)than group B(14.0%).Conclusions:Heparin is a safe and valuable treatment for patients with repeated IVF-ET failures.The clinical pregnancy and implantation rates are higher in the heparin-treated group in contrast with the control group.

Influence of Heparin on Fibrinogen Assay by Clauss Method

Objective:To investigate the effect of heparin on fibrinogen detection by Clauss method.Methods:A normal plasma pool(NPP)of 20 healthy people was prepared with 3.2%sodium citrate anticoagulant.For experimental group 1,samples containing different concentrations of heparin were prepared.For experimental group 2,samples of experimental group 1 were diluted twice.For experimental group 3,samples of experimental group 1 were diluted 4 times.For the control group,samples of normal saline with the same volume as heparin in experimental group 1 were prepared.The fibrinogen contents of experimental group 1,experimental group 2,experimental group 3,and control group were detected by Clauss method and prothrombin time(PT)-derived method,and the fibrinogen detection results of different groups were analyzed.Results:The trend of fibrinogen detected by Clauss method and PT-derived method in experimental group 1 was different;there was significant difference between the results of experimental group 1 and the control group(P<0.05);there was no significant difference between the results of experimental group 2 and the control group(P>0.05);there was no significant difference between the results of experimental group 3 and the control group(P>0.05);there was no significant difference between the results of experimental group 2 and experimental group 3(P>0.05);the relative deviation between experimental group 1 and the control group was higher in high-concentration heparin sample.Conclusion:Heparin affects fibrinogen detection by Clauss method,and the effect can be reduced by sample dilution.

2-(4-甲氧基-苯巯基)-5,8-二甲氧基萘-1,4-二酮诱导Hep3B人肝癌细胞凋亡的机制

近年来,紫草萘醌类衍生物因其临床应用受到副作用的限制。为寻找副作用小疗效高的新型抗肿瘤药物,合成了2-(4-甲氧基-苯巯基)-5,8-二甲氧基萘-1,4-二酮,并对其化学结构进行了鉴定。同时研究了2-(4-甲氧基-苯巯基)-5,8-二甲氧基萘-1,4-二酮对人肝癌细胞活力、凋亡的影响及其潜在机制。研究结果表明,通过MTT检测其细胞活力,发现2-(4-甲氧基-苯巯基)-5,8-二甲氧基萘-1,4-二酮显著降低了人肝癌细胞系的细胞活力。蛋白免疫印迹结果表明,该化合物可通过上调Cle-caspase3、Bad和Bax凋亡相关蛋白表达水平来诱导肝癌细胞Hep3B凋亡。为进一步检测2-(4-甲氧基-苯巯基)-5,8-二甲氧基萘-1,4-二酮诱导Hep3B细胞发生凋亡的原因,使用荧光探针JC-1检测了2-(4-甲氧基-苯巯基)-5,8-二甲氧基萘-1,4-二酮处理后Hep3B细胞内线粒体膜电位的变化。结果发现,与对照组相比,药物处理组线粒体膜电位显著下降,绿色荧光增强,红色荧光减弱,说明2-(4-甲氧基-苯巯基)-5,8-二甲氧基萘-1,4-二酮能通过线粒体损伤来诱导Hep3B细胞凋亡。由于2-(4-甲氧基-苯巯基)-5,8-二甲氧基萘-1,4-二酮显著诱导Hep3B细胞凋亡。因此,2-(4-甲氧基-苯巯基)-5,8-二甲氧基萘-1,4-二酮具有良好的抗肿瘤活性。

黄连素下调NRAV和PI3K/AKT通路减轻RSV感染致HEp-2细胞的损伤

目的探讨长链非编码RNA NRAV(LncRNA NRAV)和PI3K/AKT通路在黄连素(berberine,BE)减轻RSV感染致HEp-2细胞损伤中的机制。方法将HEp-2细胞感染RSV,并用BE、PI3K激活剂740Y-P处理或过表达NRAV。qRT-PCR检测NRAV、RSV-F、NS2表达水平;CCK-8实验检测细胞存活率;流式细胞术检测细胞的凋亡率和线粒体膜电位;ATP检测试剂盒检测ATP水平;Western blot检测细胞PI3K、AKT、PINK1、Parkin、Beclin1、p62、LC3Ⅰ、LC3Ⅱ、BNIP3、NLRP3、ASC、caspase-1蛋白表达;MitoSOX染色检测细胞线粒体ROS(mtROS);ELISA检测细胞IL-1β、IL-6、IL-8、TNF-α分泌水平。结果过表达NARV细胞凋亡率、RSV活性增加,敲低后结果相反;BE能显著抑制NRAV和PI3K/AKT通路(P<0.05),改善线粒体功能、诱导线粒体自噬,提高细胞的活性、降低凋亡率(P<0.05),并降低NLRP3炎性小体活化水平和IL-1β、IL-6、IL-8、TNF-α水平(P<0.05)。过表达NRAV或740Y-P处理可逆转BE对RSV感染HEp-2细胞的改善作用。结论BE能够减轻RSV感染所致HEp-2细胞损伤,其机制可能与BE下调NRAV和PI3K/AKT通路,诱导线粒体自噬,进而减轻线粒体损伤和炎症反应有关。

Heparin和CRS-heparin对小鼠黑色素瘤细胞增殖和黏附的作用研究

本实验以小鼠黑色素瘤细胞为材料,通过细胞增殖和黏附的抑制实验,对比分析了肝素(Hep-arin)和羧基还原后再硫酸化肝素(CRS-heparin)对小鼠黑色素瘤细胞增殖和黏附的影响。体外实验表明,Heparin和CRS-heparin对小鼠黑色素瘤细胞增殖都有抑制作用,并且随浓度增加抑制作用加强,但两者之间的作用差异不大。Heparin和CRS-heparin对小鼠黑色素瘤细胞与血小板之间的黏附均有抑制作用,CRS-heparin的抑制作用要稍好于Heparin,两者的抑制效果都是浓度依赖的。由于CRS-heparin的抗凝血活性明显低于Heparin,本研究结果提示,CRS-heparin可能进一步被用来作为抗肿瘤药物进行研究。

葡萄籽提取物原花青素通过LncRNA NBR2/miR-650调节EMT抑制肝癌细胞Hep3B增殖、迁移和侵袭的分子机制

目的探讨葡萄籽提取物原花青素是否通过长链非编码RNA(LncRNA)NBR2/微小RNA(miR)-650并调节上皮间充质转化(EMT)来影响肝癌细胞Hep3B的增殖、迁移和侵袭。方法将肝癌细胞Hep3B分为NC组(未处理),低、中、高剂量组(给予25、50、100μg/ml葡萄籽提取物原花青素),si-NC组,si-LncRNA NBR2组,si-NC+高剂量组、si-LncRNA NBR2+高剂量组,anti-miR-NC+si-LncRNA NBR2+高剂量组,anti-miR-650+si-LncRNA NBR2+高剂量组。采用Western印迹检测细胞周期蛋白(Cyclin)D1、基质金属蛋白酶(MMP)2、MMP9、EMT过程E-钙黏蛋白(E-cadherin)、N-钙黏蛋白(N-cadherin)、波形蛋白(Vimentin)蛋白表达,细胞计数试剂盒(CCK)-8、Transwell法和定量RT-PCR(qRT-PCR)分析细胞增殖、迁移、侵袭与LncRNA NBR2、miR-650的表达。双荧光素酶活性检测LncRNA NBR2和miR-650的靶向结合。结果低、中、高剂量组葡萄籽提取物原花青素作用的肝癌细胞Hep3B CyclinD1、MMP2、MMP9蛋白表达量、增殖能力、迁移数量、侵袭数量、miR-650表达量均低于NC组,LncRNA NBR2表达量高于NC组,差异有统计学意义(P<0.05)。高剂量组葡萄籽提取物原花青素作用的肝癌细胞Hep3B细胞中E-Cadherin蛋白表达量高于NC组,N-Cadherin、Vimentin蛋白表达量低于NC组,差异有统计学意义(P<0.05)。si-LncRNA NBR2组的肝癌细胞Hep3B细胞中CyclinD1、MMP2、MMP9蛋白表达量、增殖能力、迁移和侵袭数量均比si-NC组高,差异有统计学意义(P<0.05)。si-LncRNA NBR2+高剂量组肝癌细胞Hep3B细胞中CyclinD1、MMP2、MMP9、N-Cadherin、Vimentin蛋白表达量、增殖能力、迁移和侵袭数量均高于si-NC+高剂量组,E-Cadherin蛋白表达量低于si-NC+高剂量组,差异有统计学意义(P<0.05)。LncRNA NBR2靶向调控miR-650的表达。anti-miR-650+si-LncRNA NBR2+高剂量组肝癌细胞Hep3B CyclinD1、MMP2、MMP9、N-Cadherin、Vimentin蛋白、LncRNA NBR2表达量及增殖能力、迁移和侵袭数量均低于anti-miR-NC+si-LncRNA NBR2+高剂量组,E-Cadherin蛋白表达量高于anti-miR-NC+si-LncRNA NBR2+高剂量组,差异有统计学意义(P<0.05)。结论葡萄籽提取物原花青素通过上调LncRNANBR2靶向下调miR-650并调节EMT,来抑制肝癌细胞Hep3B的增殖、迁移和侵袭。

Meta-analysis of aspirin-heparin therapy for un-explained recurrent miscarriage

Objective This study was designed to evaluate the efficacy and safety of aspirin-heparin treatment for un-explained recurrent spontaneous abortion(URSA). Methods Literatures reporting the studies on the aspirin-heparin treatment of un-explained recurrent miscarriage with randomized controlled trials(RCTs) were collected from the major publication databases. The live birth rate was used as primary indicator, preterm delivery, preeclampsia, intrauterine growth restriction, and adverse reactions(thrombocytopenia) were used as the secondary indicators. The quality of the included studies was evaluated using RCT bias risk assessment tool in the Cochrane Handbook(v5.1.0). Meta-analysis was conducted using RevM an(v5.3) software. Subgroup analyses were conducted with an appropriately combined model according to the type of the treatments if heterogeneity among the selected studies was detected. Results Six publications of RCTs were included in this study. There were a total of 907 pregnant women with diagnosis of URSA, 367 of them were pooled in the study group with aspirin-heparin therapy and 540 women in the control group with placebo, aspirin or progesterone therapy. Meta-analysis showed that the live birth rate in the study group was significantly different from that in the control group [RR = 1.18, 95% CI(1.00-1.39), P=0.04]. Considering the clinical heterogeneity among the six studies, subgroup analysis were performed. Live birth rates in the aspirin-heparin treated groups and placebo groups were compared and no significant difference was found. There were no significant differences found between the two groups in the incidence of preterm delivery [RR=1.22, 95% CI(0.54-2.76), P=0.64], preeclampsia [RR=0.52, 95% CI(0.25-1.07), P=0.08], intrauterine growth restriction [RR=1.19, 95% CI(0.56-2.52), P=0.45] and thrombocytopenia [RR=1.17, 95% CI(0.09-14.42), P=0.90]. Conclusion This meta-analysis did not provide evidence that aspirin-heparin therapy had beneficial effect on un-explained recurrent miscarriage in terms of live birth rate, but it was relatively safe for it did not increase incidence of adverse pregnancy and adverse events. More well-designed and stratified double-blind RCT, individual-based meta-analysis regarding aspirin-heparin therapy are needed in future.

Efects of heparin on hepatic regeneration and function after partial hepatectomy in rats

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Antifibrotic effect of heparin on liver fibrosis model in rats

AIM: To evaluate the effect of chronic thrombin inhibition by heparin on experimentally induced chronic liver injury (liver fibrosis) in rats. METHODS: Chronic liver injury (liver fibrosis) was induced in Wistar rats by oral administration of carbon tetrachloride (CCl 4 ) for 7 wk, an animal model with persistent severe hepatic fibrosis. Intravenous administration of the thrombin antagonist (heparin) started 1 wk after the start of CCl 4 intoxication for 6 wk. After completion of treatment (7 wk), markers of hepatic dysfunction were measured and changes evaluated histopathologically. RESULTS: Higher serum glutamate oxaloacetate transaminase (SGOT), serum glutamate pyruvate transaminase (SGPT), alkaline phosphatase (ALP), total, direct and indirect bilirubin levels, as well as lower fibrinogen levels, were found in CCl 4 intoxicated rats. Heparin, silymarin and combination of drug (heparin and silymarin) treatment for 6 wk prevented a rise in SGOT, SGPT, ALP, total, direct and indirect bilirubin levels and improved fibrinogen levels. Deterioration in hepatic function determined by the fibrosis area was retarded, as evident from hepatic histopathology. Total protein levels were not changed in all groups.CONCLUSION: Heparin, a thrombin antagonist, preserved hepatic function and reduced severity of hepatic dysfunction/fibrogenesis. Combination of heparin and silymarin produced additional benefits on liver fibrosis.

Thrombin Generation Increasing with Age and Decreasing with Use of Heparin Indicated by Calibrated Automated Thrombogram Conducted in Chinese

Objective Calibrated Automated Thrombogram（CAT） is a test to monitor the generation of thrombin. It can be described by four parameters： lag time, peak thrombin, endogenous thrombin potential （ETP） and time to peak （ttPeak）. This study aims to determine the normal ranges of CAT parameters in Chinese, and evaluate whether thrombin generation is correlated with the concentration of heparin/Iow molecular weight heparin. Methods Plasma from 120 healthy subjects were collected to determine the normal rangea of CAT parameters in Chinese. Normal plasma pool （NPP, n=25） spiked with different concentrations of heparin or enoxaparin were used to detecte CAT parameters. The overall and age specific normal ranges of CAT parameters were calculated using descriptive statistics method with mean＋-2SD. The correlation between CAT parameters and age or concentrations of heparin, enoxaparin were analyzed with linear regression model. Results The normal ranges for lag time, peak thrombin, ETP, ttPeak in the subjects were 3.648＋2.465 min, 367.39＋151.93 nmol/L, 2277＋_1030 nmol/L.min and 6.372＋_4.280 min respectively. Age was linearly correlated with lag time （r=-0.6583, P〈0.0002）, peak thrombin （r=0.4863, P〈0.0002）, ETP （r=0.3608, P〈0.0014） and ttPeak （r=-0.6323, P〈0.0002）. The values of ETP/peak ratio were linearly correlated with concentrations of heparin. Conclusion The normal ranges of four CAT parameters for Chinese were determined. CAT parameters are associated with age. ETP/peak ratio could be used to monitor the process of anticoagulation therapy.