Heparin has been considered to be a potentially useful ligand for low-density lipoprotein（LDL） detection and analysis in a clinical context.In order to construct an affinity surface for preferential adsorption of LD...Heparin has been considered to be a potentially useful ligand for low-density lipoprotein（LDL） detection and analysis in a clinical context.In order to construct an affinity surface for preferential adsorption of LDL,heparin-modified gold surface（GS-Hep） was fabricated by a self-assembling method and hydrophobic-modified gold surfaces（GS-Hydro） was used as a control.The morphologies of the modified gold surfaces were investigated by atomic force microscopy（AFM） and the quantity of heparin bound to gold surface was assayed by the toluidine blue（TB） colorimetric method.Water contact angles were determined to investigate wettability on GS-Hep and GS-Hydro.Surface plasmon resonance（SPR） technique was used subsequently to detect the selective binding of LDL with heparin.And the investigation on the effect of pH on LDL adsorption suggests that lower pH lead to higher quantities of LDL adsorption on GS-Hep.Compared with GS-Hydro,GS-Hep is selective for LDL from both single and binary protein solutions.Moreover,adsorbed LDL on GS-Hep could be washed off by injecting elution solution,such as NaCl solution,for the purpose of the regeneration of GS-Hep for further LDL adsorption.展开更多
Objective： To investigate binding and release of vascular endothelial growth factor （VEGF） and its effect on adhesion and proliferation of endothelial cells （ECs） in acellular fresh specimens of bovine pericardiu...Objective： To investigate binding and release of vascular endothelial growth factor （VEGF） and its effect on adhesion and proliferation of endothelial cells （ECs） in acellular fresh specimens of bovine pericardiums, which were modified by heparinization. Methods： Cross-linked aeellular fresh specimens of bovine perieardiums were heparinized by three methods： （1） heparinizcd N-（3-diinethylaminopropyl）-N＇-ethylcarbodiimide hydrochloride （EDC） treated acellular tissue samples; （2） heparinized poly（ethyleneimine） （PEI） treated acellular tissue samples; （3） heparinized EDC-PEI treated aeellular tissue samples. Controlled release of VEGF and its effect on adhesion and proliferation of ECs was evaluated. Results： In the present study, binding and release of VEGF had better performance in heparinized EDC-PEI treated group, compared with heparinized EDC-alone treated group and heparinized PEI -alone group. We could observe enhanced ability to adhesion and proliferation via modest moisture and effective controlled binding and release of VEGF. Conclusion： Binding of VEGF in heparinized EDC treated group was stable, while reiease of VEGF in heparinized treated group was adjusted freely. Interestingly, controlled binding and release of VEGF could exert beneficial effect on adhesion and proliferation of ECs in heparinized EDC-PEI treated group.展开更多
In both Traditional Chinese Medicine(TCM)and modern medicine,they agree that the integrity and healthy structure of the vascular endothelium are essential for normal hemodynamics.Damage to the vascular endothelium can...In both Traditional Chinese Medicine(TCM)and modern medicine,they agree that the integrity and healthy structure of the vascular endothelium are essential for normal hemodynamics.Damage to the vascular endothelium can quickly activate the extrinsic coagulation pathway by triggering the tissue factor(TF)and lead to coagulation.This damage,along with a loss of anticoagulant properties through antithrombinⅢ(ATⅢ),TF pathway inhibitors,and the protein C system,can result in a hypercoagulable state and even thrombosis.Hypercoagulability is not only a common feature of many cancers but also an important factor promoting tumor development and metastasis,which corresponds to the TCM theory of“blood stasis leading to tumors.”The pharmacological effects of heparin and aspirin have similarities with TCM's“activating blood circulation and removing blood stasis”theory in improving blood circulation,treating related diseases,and their anti-inflammatory effects.展开更多
Heparin,a glycosaminoglycan,is a stable source of carbon that supports the growth of microorganisms in the human intestine.It is also a commonly used anticoagulant drug in clinical practice,with significant therapeuti...Heparin,a glycosaminoglycan,is a stable source of carbon that supports the growth of microorganisms in the human intestine.It is also a commonly used anticoagulant drug in clinical practice,with significant therapeutic effects.Low molecular weight heparin(LMWH)is a highly active low molecular weight fragment obtained via enzymatic reaction or the chemical degradation of heparin.LMWH has been applied globally in the prevention and treatment of venous thromboembolism in thrombosis patients.Simultaneously,as a potential prebiotic,because of its low molecular weight,LMWH can be well degraded by the gut microbiota to maintain intestinal balance.Enzymatic heparin degradation has recently emerged as a viable disposal method for LMWH preparation;however,only very few benchmark enzymes have been thoroughly described and subjected to protein engineering to improve their properties over the past few years.The commercialization of enzymes will require the development of robustly engineered enzymes that meet the demands of industrial processes.Herein,we report a rational protein engineering strategy that includes molecular dynamic simulations of flexible amino acid mutations and disulfide bond screening.Several Bacteroides thetaiotaomicron heparanase I(Bt-HepI)mutants were obtained and screened for high thermal stability.We obtained the Bt-HepI^(D204C/K208C/H189W/Q198R)variant,which features a stabilized protein surface structure,with a 1.3-fold increase in catalytic constant/michaelis-menten constant(k_(cat)/K_(m)),a 2.44-fold increase in thermal stability at 50℃,and a 1.8-fold decrease in the average molecular weight of LMWH produced at 40℃compared with that seen with Bt-HepI^(WT).Our study establishes a strategy to engineer thermostable HepI to underpin its industrial applications.展开更多
Subcutaneous administration of low-molecularweight heparin(LMWH)has been widely accepted as an effective anticoagulation therapy and is frequently used for patients to prevent thromboembolic events.While the usually s...Subcutaneous administration of low-molecularweight heparin(LMWH)has been widely accepted as an effective anticoagulation therapy and is frequently used for patients to prevent thromboembolic events.While the usually seen bruising around the injection site during subcutaneous LMWH treatment,the abdominal wall(AW)hematoma(AWH)was scarcely observed and reported.A previous study demonstrated the usual etiological risk of AWH involved anticoagulation therapy,chronic kidney disease,and trauma.^([1])Most of these cases had a favorable prognosis after conservative treatment.展开更多
BACKGROUND The risk and mortality rate of venous thromboembolism(VTE)following gastrointestinal surgery remain high,and the symptoms are atypical.Therefore,it is necessary to identify the risk factors associated with ...BACKGROUND The risk and mortality rate of venous thromboembolism(VTE)following gastrointestinal surgery remain high,and the symptoms are atypical.Therefore,it is necessary to identify the risk factors associated with the occurrence of VTE following gastrointestinal surgery and to implement appropriate prevention and treatment measures.AIM To assess the efficacy of perioperative anticoagulation for the prevention of postoperative VTE.METHODS This retrospective study enrolled 205 patients who underwent gastrointestinal surgery.In the observation group(n=101),prophylactic anticoagulation was administered via hypodermic injection of low-molecular-weight heparin during the perioperative period,whereas the control group(n=104)only received lowmolecular-weight heparin treatment postoperatively.Blood coagulation parameters and the incidence of VTE of the bilateral lower limbs pre-and post-surgery were compared between groups.Postoperative VTE was transformed into a dichotomous variable,and influencing factors were explored using multivariate logistic regression analyses.RESULTS On the 7th day postoperatively,the incidence of VTE of the bilateral lower limbs was significantly lower in the observation group than in the control group,as were the D-dimer levels(P<0.05).At 1 month postoperatively,the incidence of VTE was significantly lower in the observation group than in the control group(P<0.05).An age≥65 years,a body mass index≥24 kg/m^(2),and malignant diseases of the digestive system were identified as risk factors for the occurrence of postoperative VTE in patients undergoing gastrointestinal surgery.CONCLUSION The incidence of VTE in patients who underwent gastrointestinal surgery peaked within 1 week postoperatively.The findings confirmed perioperative anticoagulation can safely and effectively reduce the incidence of postoperative VTE.展开更多
Objective To analyze the market environment of heparin,and to provide reference for the development of the heparin industry in China.Methods The international market size and competition pattern of heparin was investi...Objective To analyze the market environment of heparin,and to provide reference for the development of the heparin industry in China.Methods The international market size and competition pattern of heparin was investigated first.Then,environmental analysis of it was made based on the PEST model.Results and Conclusion There is room for optimization of the relevant policies for the development of heparin industry in China.The use of heparin drugs and regulation should be further improved.In addition,the research and development ability of pharmaceutical enterprises should be enhanced,and the development strategy of heparin industry needs to be adjusted.展开更多
The microenvironment of the wound bed is essential in the regulation of wound repair.In this regard,strategies that provide a repairing favorable microenvironment may effectively improve healing outcomes.Herein,we att...The microenvironment of the wound bed is essential in the regulation of wound repair.In this regard,strategies that provide a repairing favorable microenvironment may effectively improve healing outcomes.Herein,we attempted to use electrical stimulation(ES)to boost the paracrine function of adipose-derived stem cells from rats(rASCs).By examining the concentrations of two important growth factors,VEGF and PDGF-AA,in the cell culture supernatant,we found that ES,especially 5𝜇A ES,stimulated rASCs to produce more paracrine factors(5𝜇A-PFs).Further studies showed that ES may modulate the paracrine properties of rASCs by upregulating the levels of TRPV2 and TRPV3,thereby inducing intracellular Ca^(2+) influx.To deliver the PFs to the wound to effectively improve the wound microenvironment,we prepared a heparinized PGA host-vip hydrogel(PGA-Hp hydrogel).Moreover,PGA-Hp hydrogel loaded with 5𝜇A-PFs effectively accelerated the repair process of the full-thickness wound model in rats.Our findings revealed the effects of ES on the paracrine properties of rASCs and highlighted the potential application of heparinized PGA host-vip hydrogels loaded with PFs derived from electrically stimulated rASCs in wound repair.展开更多
In the present study,we aimed to assess the comparative efficacy of low-molecular-weight heparin(LMWH)in combination with low-dose aspirin for the management of recurrent miscarriage and scrutinize alterations in coag...In the present study,we aimed to assess the comparative efficacy of low-molecular-weight heparin(LMWH)in combination with low-dose aspirin for the management of recurrent miscarriage and scrutinize alterations in coagulation function following such treatment.A retrospective analysis was conducted on clinical data obtained from 97 patients with recurrent miscarriage treated at our institution from January 2019 to June 2020.Patients were categorized into either the study or control groups based on the administration of LMWH.The control group comprised 48 patients treated solely with aspirin,while the study group included 49 patients treated with both LMWH and aspirin.Comparative evaluations between the two groups encompassed pregnancy outcomes,coagulation function,adverse reactions,and blood loss during delivery.Results revealed a higher term birth rate in the study group(83.67%)compared to the control group(50%).Post-treatment,the study group exhibited lower prothrombin time,plasminogen activator inhibitor,and D-dimer levels than the control group.Moreover,the study group experienced fewer adverse reactions and reduced blood loss during delivery in comparison to the control group,demonstrating statistical significance(P<0.05).The combination of LMWH and low-dose aspirin exhibited noteworthy application in the management of recurrent miscarriage.This therapeutic approach not only fostered the enhancement of coagulation function conducive to pregnancy but also diminished the incidence of adverse reactions observed with aspirin alone.展开更多
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 t...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.展开更多
BACKGROUND Bivalirudin,a direct thrombin inhibitor,is used in anticoagulation therapies as a substitute for heparin,especially during cardiovascular procedures such as percutaneous coronary intervention.AIM To explore...BACKGROUND Bivalirudin,a direct thrombin inhibitor,is used in anticoagulation therapies as a substitute for heparin,especially during cardiovascular procedures such as percutaneous coronary intervention.AIM To explore the effect of bivalirudin on myocardial microcirculation following an intervention and its influence on adverse cardiac events in elderly patients with acute coronary syndrome(ACS).METHODS In total,165 patients diagnosed with acute myocardial at our hospital between June 2020 and June 2022 were enrolled in this study.From June 2020 to June 2022,elderly patients with ACS with complete data were selected and treated with interventional therapy.The study cohort was randomly divided into a study group(n=80,administered bivalirudin)and a control group(n=85,administered unfractionated heparin).Over a 6-mo follow-up period,differences in emergency processing times,including coronary intervention,cardiac function indicators,occurrence of cardiovascular events,and recurrence rates,were analyzed.RESULTS Significant differences were observed between the study cohorts,with the observation group showing shorter emergency process times across all stages:Emergency classification;diagnostic testing;implementation of coronary intervention;and conclusion of emergency treatment(P<0.05).Furthermore,the left ventricular ejection fraction in the observation group was significantly higher(P<0.05),and the creatine kinase-MB and New York Heart Association scores were CONCLUSION In elderly patients receiving interventional therapy for ACS,bivalirudin administration led to increased activated clotting time achievement rates,enhanced myocardial reperfusion,and reduced incidence of bleeding complications and adverse cardiac events.展开更多
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 ...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.展开更多
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 pape...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.展开更多
The haemocompatibility of Ti-3Zr-2Sn-3Mo-25Nb biomedical alloy was studied after surface heparinization. A layer of sol-gel TiO2 films was applied on the alloy samples followed by active treatment in the bio-functiona...The haemocompatibility of Ti-3Zr-2Sn-3Mo-25Nb biomedical alloy was studied after surface heparinization. A layer of sol-gel TiO2 films was applied on the alloy samples followed by active treatment in the bio-functionalized solution for introducing the OH- and groups, and then the heparin was immobilized on the active TiO2 films through the electrostatic self assembly technology. It is shown that the heparinized films are mainly composed of anatase and rutile with smooth and dense surface. In vitro blood compatibility was evaluated by haemolysis test, clotting time and platelet adhesion behavior tests. The results show that the haemocompatibility of the alloy could be significantly improved by surface heparinization.展开更多
The synthesis and characterization of amphiphilic copolymers of poly（dimethyl siloxane）(PDMS),poly（ethylene oxide）(PEO), and heparin（Hep） were investigated. These multiblock copolymers wereidentified using;H-NMR...The synthesis and characterization of amphiphilic copolymers of poly（dimethyl siloxane）(PDMS),poly（ethylene oxide）(PEO), and heparin（Hep） were investigated. These multiblock copolymers wereidentified using;H-NMR, FTIR, end group analysis, and sulfur elemental analysis. The multiblockcopolymers were characterized by using DSC and X-ray diffractometry. The glass transition temperature,crystalline melting characteristics, annealing effect, and cold crystallization of the block copolymers weredetermined by DSC. The crystallinity of the block copolymers was also determined by X-ray diffractionmethod.展开更多
基金Supported by the Natural Science Foundation of Zhejiang Province of China(Nos.Y4110606 and Y1090649)the Opening Foundation of Zhejing Provincial Top Key Discipline,China(No.20110915)+1 种基金the Zhejiang Provincial Innovative Research Team,China(No.2009R50004)the Fresenius Medical Care of Deutschland GmbH’s Nephrocore Program,Germany
文摘Heparin has been considered to be a potentially useful ligand for low-density lipoprotein（LDL） detection and analysis in a clinical context.In order to construct an affinity surface for preferential adsorption of LDL,heparin-modified gold surface（GS-Hep） was fabricated by a self-assembling method and hydrophobic-modified gold surfaces（GS-Hydro） was used as a control.The morphologies of the modified gold surfaces were investigated by atomic force microscopy（AFM） and the quantity of heparin bound to gold surface was assayed by the toluidine blue（TB） colorimetric method.Water contact angles were determined to investigate wettability on GS-Hep and GS-Hydro.Surface plasmon resonance（SPR） technique was used subsequently to detect the selective binding of LDL with heparin.And the investigation on the effect of pH on LDL adsorption suggests that lower pH lead to higher quantities of LDL adsorption on GS-Hep.Compared with GS-Hydro,GS-Hep is selective for LDL from both single and binary protein solutions.Moreover,adsorbed LDL on GS-Hep could be washed off by injecting elution solution,such as NaCl solution,for the purpose of the regeneration of GS-Hep for further LDL adsorption.
文摘Objective： To investigate binding and release of vascular endothelial growth factor （VEGF） and its effect on adhesion and proliferation of endothelial cells （ECs） in acellular fresh specimens of bovine pericardiums, which were modified by heparinization. Methods： Cross-linked aeellular fresh specimens of bovine perieardiums were heparinized by three methods： （1） heparinizcd N-（3-diinethylaminopropyl）-N＇-ethylcarbodiimide hydrochloride （EDC） treated acellular tissue samples; （2） heparinized poly（ethyleneimine） （PEI） treated acellular tissue samples; （3） heparinized EDC-PEI treated aeellular tissue samples. Controlled release of VEGF and its effect on adhesion and proliferation of ECs was evaluated. Results： In the present study, binding and release of VEGF had better performance in heparinized EDC-PEI treated group, compared with heparinized EDC-alone treated group and heparinized PEI -alone group. We could observe enhanced ability to adhesion and proliferation via modest moisture and effective controlled binding and release of VEGF. Conclusion： Binding of VEGF in heparinized EDC treated group was stable, while reiease of VEGF in heparinized treated group was adjusted freely. Interestingly, controlled binding and release of VEGF could exert beneficial effect on adhesion and proliferation of ECs in heparinized EDC-PEI treated group.
基金supported by the Guizhou Provincial Basic Research Program(Natural Science)Youth Guidance Project{Qian Kehe Foundation-[2024]Youth 307}。
文摘In both Traditional Chinese Medicine(TCM)and modern medicine,they agree that the integrity and healthy structure of the vascular endothelium are essential for normal hemodynamics.Damage to the vascular endothelium can quickly activate the extrinsic coagulation pathway by triggering the tissue factor(TF)and lead to coagulation.This damage,along with a loss of anticoagulant properties through antithrombinⅢ(ATⅢ),TF pathway inhibitors,and the protein C system,can result in a hypercoagulable state and even thrombosis.Hypercoagulability is not only a common feature of many cancers but also an important factor promoting tumor development and metastasis,which corresponds to the TCM theory of“blood stasis leading to tumors.”The pharmacological effects of heparin and aspirin have similarities with TCM's“activating blood circulation and removing blood stasis”theory in improving blood circulation,treating related diseases,and their anti-inflammatory effects.
基金supported by the Natural Science Foundation of Jiangsu Province(BE2021623,BK20220155)Natural Science Foundation of Jiangsu Province(BE2021623)+4 种基金National Natural Science Foundation of China(32001665,U1903205,32021005)the National Key Research and Development Program of China(2017YF0400303)the Key Scientific and Technological Research Projects in the Key Areas of the Xinjiang Production and Construction Corps(2018AB010)the Key Research and Development 303 Program of Ningxia(2020BFG02012)Collaborative Innovation Center of Food Safety and Quality Control in Jiangsu Province。
文摘Heparin,a glycosaminoglycan,is a stable source of carbon that supports the growth of microorganisms in the human intestine.It is also a commonly used anticoagulant drug in clinical practice,with significant therapeutic effects.Low molecular weight heparin(LMWH)is a highly active low molecular weight fragment obtained via enzymatic reaction or the chemical degradation of heparin.LMWH has been applied globally in the prevention and treatment of venous thromboembolism in thrombosis patients.Simultaneously,as a potential prebiotic,because of its low molecular weight,LMWH can be well degraded by the gut microbiota to maintain intestinal balance.Enzymatic heparin degradation has recently emerged as a viable disposal method for LMWH preparation;however,only very few benchmark enzymes have been thoroughly described and subjected to protein engineering to improve their properties over the past few years.The commercialization of enzymes will require the development of robustly engineered enzymes that meet the demands of industrial processes.Herein,we report a rational protein engineering strategy that includes molecular dynamic simulations of flexible amino acid mutations and disulfide bond screening.Several Bacteroides thetaiotaomicron heparanase I(Bt-HepI)mutants were obtained and screened for high thermal stability.We obtained the Bt-HepI^(D204C/K208C/H189W/Q198R)variant,which features a stabilized protein surface structure,with a 1.3-fold increase in catalytic constant/michaelis-menten constant(k_(cat)/K_(m)),a 2.44-fold increase in thermal stability at 50℃,and a 1.8-fold decrease in the average molecular weight of LMWH produced at 40℃compared with that seen with Bt-HepI^(WT).Our study establishes a strategy to engineer thermostable HepI to underpin its industrial applications.
文摘Subcutaneous administration of low-molecularweight heparin(LMWH)has been widely accepted as an effective anticoagulation therapy and is frequently used for patients to prevent thromboembolic events.While the usually seen bruising around the injection site during subcutaneous LMWH treatment,the abdominal wall(AW)hematoma(AWH)was scarcely observed and reported.A previous study demonstrated the usual etiological risk of AWH involved anticoagulation therapy,chronic kidney disease,and trauma.^([1])Most of these cases had a favorable prognosis after conservative treatment.
文摘BACKGROUND The risk and mortality rate of venous thromboembolism(VTE)following gastrointestinal surgery remain high,and the symptoms are atypical.Therefore,it is necessary to identify the risk factors associated with the occurrence of VTE following gastrointestinal surgery and to implement appropriate prevention and treatment measures.AIM To assess the efficacy of perioperative anticoagulation for the prevention of postoperative VTE.METHODS This retrospective study enrolled 205 patients who underwent gastrointestinal surgery.In the observation group(n=101),prophylactic anticoagulation was administered via hypodermic injection of low-molecular-weight heparin during the perioperative period,whereas the control group(n=104)only received lowmolecular-weight heparin treatment postoperatively.Blood coagulation parameters and the incidence of VTE of the bilateral lower limbs pre-and post-surgery were compared between groups.Postoperative VTE was transformed into a dichotomous variable,and influencing factors were explored using multivariate logistic regression analyses.RESULTS On the 7th day postoperatively,the incidence of VTE of the bilateral lower limbs was significantly lower in the observation group than in the control group,as were the D-dimer levels(P<0.05).At 1 month postoperatively,the incidence of VTE was significantly lower in the observation group than in the control group(P<0.05).An age≥65 years,a body mass index≥24 kg/m^(2),and malignant diseases of the digestive system were identified as risk factors for the occurrence of postoperative VTE in patients undergoing gastrointestinal surgery.CONCLUSION The incidence of VTE in patients who underwent gastrointestinal surgery peaked within 1 week postoperatively.The findings confirmed perioperative anticoagulation can safely and effectively reduce the incidence of postoperative VTE.
文摘Objective To analyze the market environment of heparin,and to provide reference for the development of the heparin industry in China.Methods The international market size and competition pattern of heparin was investigated first.Then,environmental analysis of it was made based on the PEST model.Results and Conclusion There is room for optimization of the relevant policies for the development of heparin industry in China.The use of heparin drugs and regulation should be further improved.In addition,the research and development ability of pharmaceutical enterprises should be enhanced,and the development strategy of heparin industry needs to be adjusted.
基金supported by the National Natu-ral Science Foundation of China (T2288101,31971266,82272152,22075087)Guangdong Basic and Applied Basic Research Foundation (2022A1515011925)the Key Research and Development Program of Guangzhou (202007020002).
文摘The microenvironment of the wound bed is essential in the regulation of wound repair.In this regard,strategies that provide a repairing favorable microenvironment may effectively improve healing outcomes.Herein,we attempted to use electrical stimulation(ES)to boost the paracrine function of adipose-derived stem cells from rats(rASCs).By examining the concentrations of two important growth factors,VEGF and PDGF-AA,in the cell culture supernatant,we found that ES,especially 5𝜇A ES,stimulated rASCs to produce more paracrine factors(5𝜇A-PFs).Further studies showed that ES may modulate the paracrine properties of rASCs by upregulating the levels of TRPV2 and TRPV3,thereby inducing intracellular Ca^(2+) influx.To deliver the PFs to the wound to effectively improve the wound microenvironment,we prepared a heparinized PGA host-vip hydrogel(PGA-Hp hydrogel).Moreover,PGA-Hp hydrogel loaded with 5𝜇A-PFs effectively accelerated the repair process of the full-thickness wound model in rats.Our findings revealed the effects of ES on the paracrine properties of rASCs and highlighted the potential application of heparinized PGA host-vip hydrogels loaded with PFs derived from electrically stimulated rASCs in wound repair.
基金Hainan Province Health Industry Research Project(Grant No.20A200520).
文摘In the present study,we aimed to assess the comparative efficacy of low-molecular-weight heparin(LMWH)in combination with low-dose aspirin for the management of recurrent miscarriage and scrutinize alterations in coagulation function following such treatment.A retrospective analysis was conducted on clinical data obtained from 97 patients with recurrent miscarriage treated at our institution from January 2019 to June 2020.Patients were categorized into either the study or control groups based on the administration of LMWH.The control group comprised 48 patients treated solely with aspirin,while the study group included 49 patients treated with both LMWH and aspirin.Comparative evaluations between the two groups encompassed pregnancy outcomes,coagulation function,adverse reactions,and blood loss during delivery.Results revealed a higher term birth rate in the study group(83.67%)compared to the control group(50%).Post-treatment,the study group exhibited lower prothrombin time,plasminogen activator inhibitor,and D-dimer levels than the control group.Moreover,the study group experienced fewer adverse reactions and reduced blood loss during delivery in comparison to the control group,demonstrating statistical significance(P<0.05).The combination of LMWH and low-dose aspirin exhibited noteworthy application in the management of recurrent miscarriage.This therapeutic approach not only fostered the enhancement of coagulation function conducive to pregnancy but also diminished the incidence of adverse reactions observed with aspirin alone.
基金Supported by the National Natural Science Foundation of China Youth Training Project,No.2021GZR003Medical-engineering Interdisciplinary Research Youth Training Project,No.2022YGJC001.
文摘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.
文摘BACKGROUND Bivalirudin,a direct thrombin inhibitor,is used in anticoagulation therapies as a substitute for heparin,especially during cardiovascular procedures such as percutaneous coronary intervention.AIM To explore the effect of bivalirudin on myocardial microcirculation following an intervention and its influence on adverse cardiac events in elderly patients with acute coronary syndrome(ACS).METHODS In total,165 patients diagnosed with acute myocardial at our hospital between June 2020 and June 2022 were enrolled in this study.From June 2020 to June 2022,elderly patients with ACS with complete data were selected and treated with interventional therapy.The study cohort was randomly divided into a study group(n=80,administered bivalirudin)and a control group(n=85,administered unfractionated heparin).Over a 6-mo follow-up period,differences in emergency processing times,including coronary intervention,cardiac function indicators,occurrence of cardiovascular events,and recurrence rates,were analyzed.RESULTS Significant differences were observed between the study cohorts,with the observation group showing shorter emergency process times across all stages:Emergency classification;diagnostic testing;implementation of coronary intervention;and conclusion of emergency treatment(P<0.05).Furthermore,the left ventricular ejection fraction in the observation group was significantly higher(P<0.05),and the creatine kinase-MB and New York Heart Association scores were CONCLUSION In elderly patients receiving interventional therapy for ACS,bivalirudin administration led to increased activated clotting time achievement rates,enhanced myocardial reperfusion,and reduced incidence of bleeding complications and adverse cardiac events.
基金Supported by National Natural Science Foundation of China,No.82301924.
文摘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.
基金Natural Science Foundation of Xinjiang Uygur Autonomous Region(No.2019D01C244)Special Research Project for Health and Young Medical Science and Technology Talents in Xinjiang Uygur Autonomous Region(No.WJWY-202142)。
文摘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.
基金Project (31100693/C100302) supported by the National Natural Science Foundation of ChinaProject (31011120049) supported by the Australia-China Special Fund, International Science Linkages Program co-supported by the Department of Innovation, Industry, Science and Research of Australia, and the Ministry of Science and Technology and National Science Foundation of China+1 种基金Project(2010ZDKG-96) supported by the Major Subject of "13115" Programs of Shaan’xi Province, ChinaProject (2012CB619102) supported by the National Basic Research Program of China
文摘The haemocompatibility of Ti-3Zr-2Sn-3Mo-25Nb biomedical alloy was studied after surface heparinization. A layer of sol-gel TiO2 films was applied on the alloy samples followed by active treatment in the bio-functionalized solution for introducing the OH- and groups, and then the heparin was immobilized on the active TiO2 films through the electrostatic self assembly technology. It is shown that the heparinized films are mainly composed of anatase and rutile with smooth and dense surface. In vitro blood compatibility was evaluated by haemolysis test, clotting time and platelet adhesion behavior tests. The results show that the haemocompatibility of the alloy could be significantly improved by surface heparinization.
文摘The synthesis and characterization of amphiphilic copolymers of poly（dimethyl siloxane）(PDMS),poly（ethylene oxide）(PEO), and heparin（Hep） were investigated. These multiblock copolymers wereidentified using;H-NMR, FTIR, end group analysis, and sulfur elemental analysis. The multiblockcopolymers were characterized by using DSC and X-ray diffractometry. The glass transition temperature,crystalline melting characteristics, annealing effect, and cold crystallization of the block copolymers weredetermined by DSC. The crystallinity of the block copolymers was also determined by X-ray diffractionmethod.
