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.

Low-molecular-weight fucoidan inhibits the proliferation of melanoma via Bcl-2 phosphorylation and PTEN/AKT pathway

Fucoidan,a sulfate polysaccharide obtained from brown seaweed,has various bioactive properties,including anti-inflammatory,anti-cancer,anti-viral,anti-oxidant,anti-coagulant,anti-thrombotic,anti-angiogenic,and anti-Helicobacter pylori properties.However,the effects of low-molecular-weight fucoidan(LMW-F)on melanoma cell lines and three dimensional(3D)cell culture models are not well understood.This study aimed to investigate the effects of LMW-F on A375 human melanoma cells and cryopreserved biospecimens derived from patients with advanced melanoma.Ultrasonic wave was used to fragment fucoidan derived from Fucus vesiculosus into smaller LMW-F.MTT and live/dead assays showed that LMW-F inhibited cell proliferation in both A375 cells and patientderived melanoma explants in a 3D-printed collagen scaffold.The PTEN/AKT pathway was found to be involved in the anti-melanoma effects of fucoidan.Western blot analysis revealed that LMW-F reduced the phosphorylation of Bcl-2 at Thr 56,which was associated with the prevention of anti-apoptotic activity of cancer cells.Our findings suggested that LMW-F could enhance anti-melanoma chemotherapy and improve the outcomes of patients with melanoma resistance.

双凝胶在食品领域:从组成到应用

双凝胶是油凝胶和水凝胶在一定温度下剪切混合制成的双相体系。作为一种两亲性半固体制剂,双凝胶具有良好的稳定性、包埋特性、加工特性等,引起了人们的广泛关注。双凝胶在替代传统固体脂肪,提高复合食品的营养价值以及递送生物活性物质方面有巨大的潜力。本文综述了双凝胶的组成及合成方法,并梳理了双凝胶的种类,总结了双凝胶在食品领域的主要应用进展,并展望其发展前景,以期为双凝胶在食品领域的进一步研究和应用提供一定的指导。

一种有机凝胶因子对二氧化碳可视化传感的综合实验设计

合成了一种萘酰亚胺衍生的有机凝胶因子,测试了其二甲基亚砜(DMSO)凝胶在氟离子诱导下形成的溶液对气流和空气中二氧化碳可视化传感的能力。实验涉及有机合成、性能测试和仪器分析等基本操作,并利用理论知识对分子传感机理进行分析,可以培养学生多种实验技能的综合运用能力和独立分析能力。

Synthesis and Self-assembling of Coumarin-based Low-molecular Weight Organogelators

Four coumarin derivatives（4a-4d） with different alkoxy chains were synthesized. It was found that compound 4d showed a better gelation ability than the other compounds, for example, it could self-assemble into organogels in various organic fluids via ultrasound treatment or heating-cooling process, whereas compound 4c could only gel in a few mixed solvents and compounds 4a, 4b could not form organogel. The results from fluorescent and FT-IR spectra indicate that π-π interaction had an effect on the formation of the organogels of compound 4d besides H-bonding and van der Waals interaction, which were the driving forces for the self-assembling of compound 4c in gel state. The gel of compound 4d in toluene could emit strong fluorescence under UV irradiation and the [2＋2] cyclo-addition was suggested by ^1H NMR and fluorescence spectroscopy. This light-sensitive organogel might find application in optical materials.

Clinical effectiveness of a pneumatic compression device combined with low-molecular-weight heparin for the prevention of deep vein thrombosis in trauma patients:A single-center retrospective cohort study

BACKGROUND:To investigate the clinical effectiveness of a pneumatic compression device(PCD)combined with low-molecular-weight heparin(LMWH)for the prevention and treatment of deep vein thrombosis(DVT)in trauma patients.METHODS:This study retrospectively analyzed 286 patients with mild craniocerebral injury and clavicular fractures admitted to our department from January 2016 to February 2020.Patients treated with only LMWH served as the control group,and patients treated with a PCD combined with LMWH as the observation group.The incidence of DVT,postoperative changes in the visual analogue scale(VAS)score,and coagulation function were observed and compared between the two groups.Excluding the influence of other single factors,binary logistic regression analysis was used to evaluate the use of a PCD in the patient’s postoperative coagulation function.RESULTS:After excluding 34 patients who did not meet the inclusion criteria,252 patients were were included.The incidence of DVT in the observation group was significantly lower than that in the control group(5.6%vs.15.1%,χ^(2)=4.605,P<0.05).The postoperative VAS scores of the two groups were lower than those before surgery(P<0.05).The coagulation function of the observation group was significantly higher than that of the control group,with a better combined anticoagulant effect(P<0.05).There were no significant differences between the two groups in preoperative or postoperative Glasgow Coma Scale scores,intraoperative blood loss,postoperative infection rate,or length of hospital stay(P>0.05).According to logistic regression analysis,the postoperative risk of DVT in patients who received LMWH alone was 1.764 times that of patients who received LMWH+PCD(P<0.05).The area under the receiver operating characteristic(AUROC)curve of partial thromboplastin time(APTT)and platelet(PLT)were greater than 0.5,indicating that they were the influence indicators of adding PCD to prevent DVT.Excluding the influence of other variables,LMWH+PCD effectively improved the coagulation function of patients.CONCLUSIONS:Compared with LMWH alone,LMWH+PCD could improve blood rheology and coagulation function in patients with traumatic brain injury and clavicular fracture,reduce the incidence of DVT,shorten the length of hospital stay,and improve the clinical effectiveness of treatment.

Organogels, hydrogels and bigels as transdermal delivery systems for diltiazem hydrochloride

In the present study,gel formulations of organogels,hydrogels,and oleo-hydrogel(bigels)were evaluated as transdermal drug delivery systems for diltiazem HCL(DH).Organogels were prepared using soya-bean oil(SO)as a solvent and span 60(Sp 60),cetyl alcohol(CA)or lecithinpluronic(PLO)as organogelators without and with different surfactants(2%w/w)namely span 80(Sp80),tween 20(T20)and tween 80(T80).On the other hand,hydrogels were formulated using Hydroxypropyl-methylcellulose(HPMC)polymer and bigels were prepared by mixing organogels with HPMC hydrogels.The prepared gels were analyzed microscopically,thermally by DTA and for pH,and viscosity.The effect of gelator used,surfactant types and pH of the sink on DH release from cellophane membrane was investigated.In addition,the DH permeability across the rabbit skin was evaluated.Finally,the in vivo performance of various gel formulationswas assessed based on the hypotensive effects of the drug using hypertensive albino male rat models.The microscopical analysis indicated that the solid fibers formed by gelator particles form the backbone of the organogels while bigels appeared as emulsion like.The addition of surfactants showed an increase in organogel viscosity.The thermal analysis of organogels indicated that the drug present in amorphous not in crystalline form.The release studies indicated that DH release from organogels,hydrogels and bigels could be controlled.The included surfactants decreased the DH release and permeation from organogels compared to those without surfactants using either Sp60 or CA.HPMC hydrogel and Bigels showed higher DH release and permeation rates when compared to organogels.The percent DH released in different pH values was in the following descending order:pH5.5>pH1.2>pH6.8>pH7.4.The in vivo antihypertensive activity of DH using different transdermal gels is arranged as following:hydrogels>PLO organogel>bigel>Sp 60 organogel.

Attenuation of corneal neovascularization by topical low-molecular-weight heparin-taurocholate 7 without bleeding complication

AIM：To investigate the antiangiogenic effects and safety of topically administered low-molecular-weight heparintaurocholate 7（LHT7） on corneal neovascularization（CoNV）.METHODS：Twenty-four Sprague-Dawley rats were randomly distributed into four groups of six rats each.The central corneas were cauterized using a silver/potassium nitrate solution.From 2d after cauterization,12.5 mg/mL（low LHT7 group） or 25 mg/mL（high LHT7group） LHT7 was topically administered three times daily;12.5 mg/mL bevacizumab was topically administered as positive control（bevacizumab） group,with normal saline（NS） administered as negative control（NS group）.The corneas were digitally photographed to calculate the CoNV percentage from the neovascularized corneal area at 1 and 2wk.RESULTS：The 4 study groups did not have different CoNV percentages at 1wk after injury（P〉0.05）.However,the low LHT,high LHT,and bevacizumab groups had significantly lower CoNV percentages than the NS group at 2wk（all P〈0.05）.No significant differences in CoNV percentage were found among the low LHT,high LHT,and bevacizumab groups（all P〉0.05）.All groups except the NS group had lower CoNV percentages at 2wk postinjury than the levels observed at 1wk（all P〈0.05）.CONCLUSION：Topically-administered LHT7 inhibited CoNV without complication after chemical cauterization in the rat.

Fluoride-Responsive Organogel Based on Hydrazide Derivatives

An organogelator named N-[3-(hydroxy)-4-(dodecyloxy)-benzoyl]-N’ (4’-nitro-benzoyl) hydrazide (D12) was synthesized. It could form stable gels in some of the tested organic solvent. SEM images revealed that the molecules self- assembled into fibrous aggregates in the xerogels. The X-ray diffraction analysis showed that the xerogel exhibited a layered structure. FT-IR studies confirmed that intermolecular hydrogen bonding between C=O and N-H groups was the major driving force for gelation of organic solvents. The gel exhibited gel-sol transition and color change upon addition of F- . An extended conjugated system formed through the phenyl group and a five-membered ring based on intramolecular hydro-gen bonding between the oxygen atom near the deprotonation nitrogen atom and the other NH, which is responsible for the dramatic color change upon addition of F- .

Combined effect of Traditional Chinese Medicine decoction and low-molecular-weight heparin calcium on the postoperative deep venous thrombosis in patients with lower limb fracture

OBJECTIVE: To investigate the combined effect of Traditional Chinese Medicine(TCM) decoction and low-molecular-weight heparin calcium on deep vein thrombosis(DVT) induced by surgery in patients with lower limb fracture.METHODS: Totally 86 hospitalized patients with DVT after surgery of lower limb fracture between September 2012 and January 2015 were recruited and randomly divided into control group and observation group, 43 cases in each group. The patients in the control group were treated with subcutaneous injection of low-molecular-weight heparin calcium, and those in the observation group were additionally given Danshen Injection and TCM decoction. The differences between two groups in occurrence rate, medication time, therapeutic effects,recurrence rate of thrombosis, activated partial thromboplastin time(APTT), and prothrombin time(PT) were compared.RESULTS: The occurrence rate of DVT in observation group(4.65%, 2/43) was lower than that in control group(27.91%,12/43)(P<0.05). The medication time of observation group was(6.15±2.94) d, shorter than(9.76±3.12) d in the control group(P<0.05). In observation group, 2 cases of DVT were cured(2/2); in the control group, 9 cases presented therapeutic effects and the total effective rate was 75.00%(9/12). The improvement of APTT and PT in the observation group was better than that in the control group(P<0.05).CONCLUSION: Integrative TCM decoction plus low-molecularweight heparin calcium is superior to applicaton of low-molecularweight heparin calcium alone in reducing and treating DVT in the postoperative patients with lower limb fracture.

The Safety and Feasibility of Low-Molecular-Weight He-parin Prophylaxis in Major Abdominal Surgery Combined with Neuraxial Anesthesia

Background: Global guidelines for venous thromboembolism (VTE) prophylaxis of patients undergoing major surgery are well established. However, their applicability and safety in patients receiving neuraxial anesthesia is unproven. We sought to evaluate the safety and feasibility of chemical VTE prophylaxis in a prospective group of patients undergoing major foregut procedures under a combination of epidural and general anesthesia. Methods: A prospective database of all patients undergoing major foregut surgery from 2004-2009 was maintained and analyzed. Epidural catheters were placed pre-operatively and used for post-operative analgesia for three days in all patients. Factors evaluated included age, ethnicity, sex, length of stay, duration of epidural placement, complications of epidural placement and post-operative management, and VTE events. A uniform protocol was followed regarding the timing of low-molecular-weight heparin (LMWH) administration with epidural catheter insertion/removal. Results: A total of 237 patients formed the study group. The mean age was 57 years (range, 19 - 88) among 121 (51.1%) women and 65 years (range, 20 - 95) among 116 (48.9%) men. One hundred and sixty-six patients were Caucasian (70%), 37 Black (15.6%), 15 Hispanic (6.3%), 12 Asian/Pacific (5.1%), and 7 other (3%). All epidural catheters were removed on the third post-operative day. There were a total of five VTE (2.1%) events postoperatively. No peri-operative or post-operative epidural catheter associated complications occurred. Conclusions: Concomitant epidural catheterization and LMWH anticoagulation is safe and feasible in major abdominal surgery patients, including those undergoing major hepatic resection. Guidelines for VTE prophylaxis and LMWH administration in the setting of neuraxial anesthesia are well established and applicable to this unique patient population.

Utilizing Water Treatment Residuals for Phosphorus Removal:Batch Trials,Column Trials and Effects of Three Low-Molecular-Weight Organic Acids

Phosphorus( P) has been recognized as a major limited nutrient responsible for the eutrophication of surface waters. Water treatment residuals( WTRs) are safe by-products of water treatment plants and are cost-efficient adsorbents. In this study, batch experiments and column experiments based on WTRs were employed to study the characteristics of P adsorption and the effects of lowmolecular-weight organic acids( LMWOAs)( citric acid, oxalic acid,and tartaric acid) on P adsorption. Different models of adsorption were used to describe equilibrium and kinetic data. The adsorption data were fitted well by a pseudo-second order kinetic model. The adsorption process was determined to be controlled by three steps of diffusion mechanisms through the intra-particle model.The adsorption equilibrium was well described by the Langmuir,Freundlich,Redlich-Peterson,and Sips isotherm models. Batch and continuous flow experiments indicated that the LMWOAs exhibited inhibitory action,and as pH increased,the inhibitory action became weaker for all the three acids. The effect of LMWOAs concentration was not significant on inhibition. The effects of LMWOAs were closely related to reaction time.

Impact of Pharmaceutical Care on Self-Administration of Outpatient Low-Molecular-Weight Heparin Therapy

Outpatient subcutaneous (s.c.) therapies are becoming more and more common in the treatment of different diseases. The effectiveness of community-pharmacy-based interventions in preventing problems that arise during s.c. self-injections of low-molecular-weight heparins (LMWH) is unknown. Our objective was to provide a standard operating procedure (SOP) for community pharmacists and to compare pharmaceutical vs. standard care in both clinical and daily life settings. We hypothesized that: pharmaceutical care results in improved adherence, safety, and satisfaction, and in fewer complications;the interventions used are feasible in daily life;and the results achieved in clinical and daily life settings are comparable. In the clinical setting (randomized controlled trial), patients were recruited sequentially in hospital wards;in the daily life setting (quasi-experimental design with a comparison group), recruitment took place in community pharmacies by pharmacists and trained master students during their internship. Interventions were offered according to patient needs. Data were collected by means of a monitored self-injection at home and structured questionnaire-based telephone interviews at the beginning and the end of the LMWH treatment. The main outcome measures were: scores to assess patient’s skills;syringe count to assess adherence;and frequency, effectiveness, and patient’s assessment of received interventions. The results show a median age of the 139 patients of 54 years. Interventions resulted in improved application quality (p p = 0.03). Oral instructions were pivotal for improving patients’ application quality. We found no significant score differences between the intervention groups in the clinical and daily life settings. Patients’ baseline skills were high, with the lowest score being 0.86 (score range ?2.00 to +2.00). Adherence rate was high (95.8%). In conclusion, our SOP for pharmacist interventions was of good quality, adequate, appreciated, and feasible in daily life. Patients are capable of managing s.c. injection therapies if adequate assistance is provided.

Evaluation of a Dose-Monitoring Method for Prophylactic Anticoagulant Therapy with Low-Molecular-Weight Heparin

Objective: In the present study, we report on the results of our investigation of optimum dose monitoring using coagulation and fibrinolytic system indicators during obstetric prophylactic anticoagulant therapy with enoxaparin. Study Design: Of 103 cases of cesarean section performed at our hospital, 37 cases were selected for this study after obtain ing their consent for blood collection. Variables of the coagulation and fibrinolytic systems [anti-factor Xa activity, endogenous thrombin potential (ETP), prothrombin time (PT) or international normalized ratio (INR), activated partial thromboplastin time (APTT) and D-dimer levels] were determined. Results: In the 5-day administration group, the anti-factor Xa activitywas 0.0 U/ml on the postoperative day 1, increased to 0.05 U/ml ± 0.04 U/ml on the postoperative day 3, and mildly increased to 0.06 U/ml ± 0.05 U/ml on the postoperative day 5. On the other hand, the anti-factor Xa activity in the 3-day administration group was 0.0 U/ml on the postoperative day 1 (before enoxaparin administration), increased to 0.06 U/ml ± 0.05 U/ml on the postoperative day 3, and significantly decreased to 0.02 U/ml ± 0.03 U/ml on the postoperative day 5 (p = 0.003);thus, the pattern of change was significantly different from that in the 5-day administration group (p = 0.004). Enoxaparin administration did not result in any significant fluctuation of the ETP, and no significant difference was observed between the 5-day and 3-day administration groups. Conclusion: Enoxaparin administration was associated with increase of the anti-factor Xa activity, and prolonged administration led to more sustained increase of the activity.

Effect of adjuvant low-molecular-weight heparin therapy on placental hypoxia and cell apoptosis in puerperae with severe preeclampsia

Objective:To study the effect of adjuvant low-molecular-weight heparin therapy on placental hypoxia and cell apoptosis in puerperae with severe preeclampsia.Methods:A total of 94 puerperae with severe preeclampsia who received treatment and safely gave birth in our hospital between May 2014 and May 2016 were selected as the research subjects and randomly divided into the LMWH group who received low-molecular-weight heparin combined with conventional symptomatic treatment and the control group who received conventional symptomatic treatment. Before and after treatment, serum was collected respectively to determine the levels of placental hypoxia-related cytokines, and after delivery, the placentas were collected to detect oxidative stress indexes and cell apoptosis indexes.Results: After treatment, serum PLGF and PAPP-A levels of both groups were significantly higher than those before treatment while sFlt-1 and sEng levels were significantly lower than those before treatment, and after treatment, serum PLGF and PAPP-A levels of LMWH group were significantly higher than those of control group while sFlt-1 and sEng levels were significantly lower than those of control group;ROS and RNS levels as well as Fas, FasL, caspase-3 and caspase-8 protein expression in placenta tissue of LMWH group were significantly lower than those of control group while GPx-1, SOD-1 and Trx levels as well as Survivin, XIAP and Bcl-2 protein expression were significantly higher than those of control group.Conclusion:Adjuvant low-molecular-weight heparin therapy can relieve the placental hypoxia, improve oxidative stress reaction and inhibit cell apoptosis in puerperae with severe preeclampsia.

刺激响应性聚集诱导发光凝胶因子的设计、合成及性能

与聚合物凝胶相比,有机小分子凝胶易于化学改性,具有更好的刺激响应,在众多领域显示出巨大的应用潜力。本文以没食子酸、单羧基四苯乙烯为基本原料,合成得到一种兼具聚集诱导发光性质和还原刺激响应性凝胶因子G1。凝胶因子G1能在环己烷和二甲基亚砜(DMSO)中自组装形成凝胶,临界成胶浓度分别为5.6mg/mL和16.7mg/mL。紫外光谱、荧光光谱、红外光谱、变温核磁、X射线衍射(XRD)研究结果表明,π-π堆积和氢键作用是凝胶因子G1形成凝胶的主要驱动力。此外,接触角研究结果表明,凝胶因子G1在DMSO中形成的干凝胶薄膜的接触角高达137°,表明其具有较强的疏水性,在刺激响应性荧光疏水材料领域有着潜在的应用价值。

油凝胶替代固体脂肪在食品中应用研究进展

对油凝胶的特性、形成机理及有机凝胶因子进行了综述,并对油凝胶替代固体脂肪在食品中的应用前景和挑战进行探讨,以期为油凝胶的进一步研究和应用提供参考。

新型乳化体系及其在化妆品中的应用(Ⅱ)——双凝胶体系

双凝胶体系是一种在不添加(或少量添加)表面活性剂的情况下,将一种液体以凝胶的形式(如油凝胶或水凝胶)分散在另一种与其不相容的凝胶(如水凝胶或油凝胶)中的特殊乳化体系。该体系兼具水凝胶和油凝胶的双重优势,不仅能同时递送亲水性和亲油性物质,而且展现出比单一凝胶更优异的性能。加之体系中不含(或含少量)表面活性剂,不会引起对敏感肌肤的刺激和脱水问题,使其在化妆品领域具有广阔的应用前景。本文首先介绍了凝胶及双凝胶体系;总结了影响双凝胶体系性质的因素,包括凝胶剂、油/水凝胶比例、油脂性质以及制备工艺等;归纳了双凝胶产品的皮肤安全性、稳定性、锁水保湿性、缓释性及肤感等。在此基础上,阐述了双凝胶体系在化妆品领域应用的研究进展。最后指出了目前双凝胶体系在化妆品领域应用中所面临的问题,并对后续亟待解决的问题提出了个人看法,旨在为性能优异的双凝胶产品的开发及应用提供基础信息,为双凝胶体系的发展方向提供参考。

胆固醇修饰的氨基酸类有机凝胶因子去除水中亚甲基蓝的研究

设计合成了胆固醇修饰的氨基酸类有机凝胶因子CH-1和CH-2,并对其去除水中的亚甲基蓝进行了系统地研究.结果表明,CH-2粉末能够去除水中的亚甲基蓝,CH-1与低毒的苯甲醇形成的凝胶也可以快速去除水中的亚甲基蓝.

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.