Objective:To investigate the effects of infrared lamp irradiation therapy on the risk of arteriovenous fistula thrombosis in patients undergoing heparin-free dialysis and those receiving appropriate reductions in hepa...Objective:To investigate the effects of infrared lamp irradiation therapy on the risk of arteriovenous fistula thrombosis in patients undergoing heparin-free dialysis and those receiving appropriate reductions in heparin anticoagulation dosage during dialysis.Methods:This study was conducted from January 1,2021,to December 31,2021,involving 19 patients who regularly underwent heparin-free dialysis for more than three months at our hospital,totaling 70 patient encounters.Each patient underwent heparin-free dialysis for more than two cycles during the experimental period.The study employed a self-control design.Prior to the experiment,an experienced medical team established an emergency management group and formulated relevant emergency measures,ensuring the long-term stability of patients’vital signs before enrollment.Patients requiring heparin-free dialysis as per medical advice underwent the procedure according to the treatment manual without additional interventions.During the second heparin-free dialysis session within the experimental period,patients received 40 minutes of infrared lamp irradiation as an adjunctive therapy during the dialysis process.The study observed coagulation in the dialyzer,blood biochemical indicators,the occurrence of adverse reactions,and patient satisfaction during treatment.Results:The use of heparin-free dialysis combined with infrared irradiation therapy resulted in better coagulation outcomes compared to heparin-free dialysis alone(p<0.05).There was no statistically significant difference in blood biochemical indicators between patients receiving heparin-free dialysis combined with infrared irradiation therapy and those receiving heparin-free dialysis alone(p>0.05).There was no statistically significant difference in the number of patients experiencing adverse clinical symptoms such as angina,dizziness,and lower limb cramps,leading to treatment interruption,between those receiving heparin-free dialysis combined with infrared therapy and those receiving heparin-free dialysis alone(p>0.05).Patient satisfaction was higher among those receiving heparin-free dialysis combined with infrared therapy compared to those receiving heparin-free dialysis alone(p<0.05).Conclusion:The use of infrared lamp irradiation therapy as an adjunct to heparin-free dialysis can reduce the risk of coagulation to a certain extent without affecting the stability of core blood biochemical indicators in patients.It also reduces the incidence of clinical adverse reactions caused by coagulation,demonstrating good safety and improving patient satisfaction.展开更多
Two supramolecular organic frameworks(SOFs)have been constructed from the co-assembly of biimidazolium-derived octacationic components and cucurbit[8]uril in water.Dynamic light scattering and ^(1)H NMR experiments re...Two supramolecular organic frameworks(SOFs)have been constructed from the co-assembly of biimidazolium-derived octacationic components and cucurbit[8]uril in water.Dynamic light scattering and ^(1)H NMR experiments reveal that both SOFs can undergo reversible assembly and disassembly at room temperature.One of the SOFs displays unprecedently high maximum tolerated dose of 120 mg/kg with mice,which improves by 40%compared with the highest value of the reported SOFs.In vitro and in vivo tests show that the SOF can adsorb doxorubicin and overcome the resistance of multidrugresistant MDR A549/ADR tumor cells to realize intracellular delivery,leading to enhanced antitumor efficacy.Moreover,it can also completely inhibit the posttreatment phototoxicity of photofrin and fully neutralize the anticoagulation of both unfractionated heparin and low molecular weight heparins through efficient inclusion and elimination or sequestration mechanism.As the first examples that undergo roomtemperature reversible assembly and disassembly,the new SOFs in principle allow for quantitative analysis of the molecular components in the body that is prerequisite for preclinical evaluation in the future.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
Corresponding author’s name was incorrectly written as“Dadang Guo”instead of“Dagang Guo”.The correct author name should be“Dagang Guo”.The authors would like to apologise for any inconvenience caused.
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
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
Exposure to heparin is associated with a high incidence of immunization against platelet factor 4(PF4)/heparin complexes. A subgroup of immunized patients is at risk of developing heparin-induced thrombocytopenia(HIT)...Exposure to heparin is associated with a high incidence of immunization against platelet factor 4(PF4)/heparin complexes. A subgroup of immunized patients is at risk of developing heparin-induced thrombocytopenia(HIT), an immune mediated prothrombotic adverse drug effect. Transplant recipients are frequently exposed to heparin either due to the underlying end-stage disease, which leads to listing and transplantation or during the transplant procedure and the perioperative period. To review the current scientific knowledge on antiheparin/PF4 antibodies and HIT in transplant recipients a systematic Pub Med literature search on articles in English language was performed. The definition of HIT is inconsistent amongst the publications. Overall, six studies and 15 case reports have been published on HIT before or after heart, liver, kidney, and lung transplantation, respectively. The frequency of seroconversion for anti-PF4/heparin antibodies ranged between 1.9% and 57.9%. However, different methods to detect anti-PF4/heparin antibodies were applied. In none of the studies HIT-associated thromboembolic events or fatalities were observed. More importantly, in patients with a history of HIT, reexposure to heparin during transplantation was not associated with thrombotic complications. Taken together, the overall incidence of HIT after solid organ transplantation seems to be very low. However, according to the current knowledge, cardiac transplant recipients may have the highest risk to develop HIT. Different alternative suggestions for heparin-free anticoagulation have been reported for recipients with suspected HIT albeit no official recommendations on management have been published for this special collective so far.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
Heparin-induced thrombocytopenia(HIT) is a relatively infrequent complication of heparin administration. HIT can cause devastating thrombosis, making it one of the most serious adverse drug reactions encountered in cl...Heparin-induced thrombocytopenia(HIT) is a relatively infrequent complication of heparin administration. HIT can cause devastating thrombosis, making it one of the most serious adverse drug reactions encountered in clinical practice. We successfully treated a case of severe HIT presenting with thrombosis and life-threatening bleeding complications with intravenous immunoglobulin(IVIG), platelet transfusion and oral anticoagulant Rivaroxaban. In this case, we considered that IVIG played the most important role by preventing further thrombosis, increasing the platelet count, and ensuring the efficacy of Rivaroxaban. We therefore suggest that IVIG might be the optimal treatment for patients with this urgent condition.展开更多
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 pe...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.展开更多
Objective: Acute pulmonary thromboembolism (PTE) is a serious high mortality pulmonary vascular disease whose effective treatment decreases morbidity and mortality. To determine if low-molecular-weight-heparin (LMWH) ...Objective: Acute pulmonary thromboembolism (PTE) is a serious high mortality pulmonary vascular disease whose effective treatment decreases morbidity and mortality. To determine if low-molecular-weight-heparin (LMWH) is clinically as efficient and safe as unfractionated heparin (UH) in patients with diagnosis of acute non-massive PTE, our study compares the efficacy, adverse effects and costs of LMWH and UH. Methods: One hundred and fourteen patients with non-massive acute PTE were randomly divided into LMWH (nadroparin calcium) and UH groups. Oxygenation index, D-dimer, fibrinogen (FG), lung ventilation/perfusion (V/Q) scan and computed tomography pulmonary angiography (CTPA) were observed before anticoagula-tion and on day 14 after anticoagulation. Results: In both groups, the ABG (arterial blood gas) analysis showed PaO2 and PaCO2 were elevated, P(A-a)O2 was decreased and oxygenation index (PaO2/FIO2) was elevated, D-dimer and fibrinogen were decreased, lung V/Q and CTPA showed embolized segments reduced (P<0.05). Hemorrhage and thrombocytopenia occurred in 3.5% of the LMWH group. Hemorrhage occurred in 5.3% and thrombocytopenia occurred in 7.0% of the UH group. The average cost in the LMWH group was RMB 1218.60 Yuan and RMB 1541.40 Yuan in the UH group. Conclusion: LMWH and UH are equally effective for treatment of non-massive acute PTE, but LMWH may have a lower prevalence of complications and is less expen-sive.展开更多
Biomedical molecule has received extensive application in surface modification coating.In this paper,polyethyleneimine （PEI）/heparin coating and chitosan/heparin coating on NiTi alloy substrates were prepared by lay...Biomedical molecule has received extensive application in surface modification coating.In this paper,polyethyleneimine （PEI）/heparin coating and chitosan/heparin coating on NiTi alloy substrates were prepared by layer-by-layer method,and differences of corrosion behavior and biocompatibility of the coatings were studied.Static contact angles and Fourier transform infrared （FT-IR） test were used to analysis the surface morphology and structure character of the materials,and atomic absorption spectrum was used to verify the corrosion behavior of the materials.Furthermore,hemolysis,dynamic clotting time and platelet binding test were utilized to investigate the biocompatibility of the materials.The results revealed that the blood compatibility of PEI/heparin coating is better than that of the chitosan/heparin coating as well as the substrate.展开更多
Objective: To survey the effects of inhaled heparin on airway inflammation inguinea pigs with asthma and investigate the possible mechanism of inhaled heparin in the treatmentof asthma. Methods: The asthma in guinea p...Objective: To survey the effects of inhaled heparin on airway inflammation inguinea pigs with asthma and investigate the possible mechanism of inhaled heparin in the treatmentof asthma. Methods: The asthma in guinea pigs induced by ovalbumin was treated with inhaled heparin.The changes of cellularities in bronchoalveolar lavage (BAL) fluid and the airway walls wereexamined. Histologic examinations were also done in the guinea pig controls. Results: The number ofeosinophils, lymphocytes, and ciliated epithelial cells in the BAL fluid from the group treated withheparin was significantly lower than that of the group of asthma controls (P<0.01). Within theairway watts of the heparin treated group, the eosinophil infiltration was less prominent than thatof the group of asthma controls (P<0.001) and the number of mast cell was significantly higher thanthat of the group of asthma controls (P<0.01). Histologic examination showed that airway damages inthe heparin treated group were mild. Conclusion: Heparin can inhibit airway inflammation andalleviate airway damage in guinea pigs with asthma.展开更多
Aim: The objective of this study is to review all the reported outcomes of heparin application in amniotic fluid embolism (AFE) so far and to find out why, when and how heparin or other anticoagulants should be used i...Aim: The objective of this study is to review all the reported outcomes of heparin application in amniotic fluid embolism (AFE) so far and to find out why, when and how heparin or other anticoagulants should be used in AFE. Material and methods: We searched Medline (from 1969 to 2011), using two key words: 1) amniotic fluid embolism;2) amniotic fluid embolism and heparin. The search for the former produced 1127 replies, of which 208 were case reports of AFE. In response to the other key word, there were 94 articles. We looked through all the articles, selecting those relevant for our study. Results: In the years 1969-2011, 208 AFE cases were reported. Heparin (unfractionated heparin) or low molecular weight heparin (LMWH) was applied in 20 cases (9.6%), being the main drug in 11 cases (5.3%) and in 6 cases as a component of spectacular treatment of AFE (surgical treatment and extracorporal membrane oxygenation). In one of these cases anithrombin (AT) with LMWH was used. In one patient heparin therapy was considered to be unsuccessful and hence recombinant plasminogen activator (rt-PA) was instituted. All the patients survived. Conclusions: 1) The attempts to use heparin in AFE could be defined as promising, although the number of treated patients is too small for conclusion;2) The postulate to use heparin at the very onset of AFE (a bolus of 10,000 U followed by monitored intravenous infusion) has serious justification: one of the pathways of AFE is the target for heparin (coagulation pathway).展开更多
Objective Heparin-induced thrombocytopenia(HIT)is a complication characterized by thrombocytopenia,hemorrhage and/or thrombosis,which is caused by initial or repeated application of unfractionated heparin(UFH)and low-...Objective Heparin-induced thrombocytopenia(HIT)is a complication characterized by thrombocytopenia,hemorrhage and/or thrombosis,which is caused by initial or repeated application of unfractionated heparin(UFH)and low-molecular-weight heparin(LMWH).This study aims to summarize the clinical features of HIT in patients undergoing cardiac surgery.展开更多
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 u...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.展开更多
Heparin-induced thrombocytopenia (HIT) is a clinicopathologic syndrome because diagnosis is based on both clinical symptoms and laboratory data. We report a patient with multiple thromboembolic complications after dai...Heparin-induced thrombocytopenia (HIT) is a clinicopathologic syndrome because diagnosis is based on both clinical symptoms and laboratory data. We report a patient with multiple thromboembolic complications after daily flushing of intravenous line with small amounts of unfractionated heparin (UFH). At day 7 bilateral hemorrhagic infarction of the adrenal glands was misdiagnosed as adrenal adenoma. On day 10 thrombocytopenia was noted and the next day a myocardial infarction complicated by a left ventricular thrombus was diagnosed. On day 12, HIT was suspected. The pre-test probability for HIT according to the 4T-score was high (8/8 points) and detection of antibodies directed against the PF4/heparin-complex by particle gel immunoassay (Titer 1:1024) and ELISA (O.D. 2.784) was strongly positive. HIT can be induced by iv-line flushes with UFH. Arterial and venous thrombotic complications can be present before a clear platelet drop can be recognised.展开更多
As one of the most commonly used anticoagulants, heparin plays an important role in the prevention and treatment of venous thrombosis. After many studies and demonstrations, we found that heparin mainly shows its biol...As one of the most commonly used anticoagulants, heparin plays an important role in the prevention and treatment of venous thrombosis. After many studies and demonstrations, we found that heparin mainly shows its biological activity by interacting with a variety of proteins. Heparins not only have anticoagulant effects, but also have good pharmacological effects in anti-tumor, anti-inflammatory, anti-virus, wound healing and anti anemia. On this basis, LMWH also has the advantages of good absorption, high bioavailability, long half-life, etc., so the clinical application of LMWH continues to expand. In recent years, there are many reports about low molecular weight heparin in the research work of heparin at home and abroad. This article mainly discusses the mechanism of action and clinical application of the above heparin drugs.展开更多
基金2023 Hospital-Level Scientific Research and New Technology Project Initiation of Wuzhong People’s Hospital(Project No.:2023yjxjs05)。
文摘Objective:To investigate the effects of infrared lamp irradiation therapy on the risk of arteriovenous fistula thrombosis in patients undergoing heparin-free dialysis and those receiving appropriate reductions in heparin anticoagulation dosage during dialysis.Methods:This study was conducted from January 1,2021,to December 31,2021,involving 19 patients who regularly underwent heparin-free dialysis for more than three months at our hospital,totaling 70 patient encounters.Each patient underwent heparin-free dialysis for more than two cycles during the experimental period.The study employed a self-control design.Prior to the experiment,an experienced medical team established an emergency management group and formulated relevant emergency measures,ensuring the long-term stability of patients’vital signs before enrollment.Patients requiring heparin-free dialysis as per medical advice underwent the procedure according to the treatment manual without additional interventions.During the second heparin-free dialysis session within the experimental period,patients received 40 minutes of infrared lamp irradiation as an adjunctive therapy during the dialysis process.The study observed coagulation in the dialyzer,blood biochemical indicators,the occurrence of adverse reactions,and patient satisfaction during treatment.Results:The use of heparin-free dialysis combined with infrared irradiation therapy resulted in better coagulation outcomes compared to heparin-free dialysis alone(p<0.05).There was no statistically significant difference in blood biochemical indicators between patients receiving heparin-free dialysis combined with infrared irradiation therapy and those receiving heparin-free dialysis alone(p>0.05).There was no statistically significant difference in the number of patients experiencing adverse clinical symptoms such as angina,dizziness,and lower limb cramps,leading to treatment interruption,between those receiving heparin-free dialysis combined with infrared therapy and those receiving heparin-free dialysis alone(p>0.05).Patient satisfaction was higher among those receiving heparin-free dialysis combined with infrared therapy compared to those receiving heparin-free dialysis alone(p<0.05).Conclusion:The use of infrared lamp irradiation therapy as an adjunct to heparin-free dialysis can reduce the risk of coagulation to a certain extent without affecting the stability of core blood biochemical indicators in patients.It also reduces the incidence of clinical adverse reactions caused by coagulation,demonstrating good safety and improving patient satisfaction.
基金the National Natural Science Foundation of China(No.21921003 for Z.T.L.and 22201293 for S.B.Y.)Shanghai Sailing Program(No.22YF1458300 for S.B.Y.)for financial support。
文摘Two supramolecular organic frameworks(SOFs)have been constructed from the co-assembly of biimidazolium-derived octacationic components and cucurbit[8]uril in water.Dynamic light scattering and ^(1)H NMR experiments reveal that both SOFs can undergo reversible assembly and disassembly at room temperature.One of the SOFs displays unprecedently high maximum tolerated dose of 120 mg/kg with mice,which improves by 40%compared with the highest value of the reported SOFs.In vitro and in vivo tests show that the SOF can adsorb doxorubicin and overcome the resistance of multidrugresistant MDR A549/ADR tumor cells to realize intracellular delivery,leading to enhanced antitumor efficacy.Moreover,it can also completely inhibit the posttreatment phototoxicity of photofrin and fully neutralize the anticoagulation of both unfractionated heparin and low molecular weight heparins through efficient inclusion and elimination or sequestration mechanism.As the first examples that undergo roomtemperature reversible assembly and disassembly,the new SOFs in principle allow for quantitative analysis of the molecular components in the body that is prerequisite for preclinical evaluation in the future.
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Corresponding author’s name was incorrectly written as“Dadang Guo”instead of“Dagang Guo”.The correct author name should be“Dagang Guo”.The authors would like to apologise for any inconvenience caused.
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.
文摘Exposure to heparin is associated with a high incidence of immunization against platelet factor 4(PF4)/heparin complexes. A subgroup of immunized patients is at risk of developing heparin-induced thrombocytopenia(HIT), an immune mediated prothrombotic adverse drug effect. Transplant recipients are frequently exposed to heparin either due to the underlying end-stage disease, which leads to listing and transplantation or during the transplant procedure and the perioperative period. To review the current scientific knowledge on antiheparin/PF4 antibodies and HIT in transplant recipients a systematic Pub Med literature search on articles in English language was performed. The definition of HIT is inconsistent amongst the publications. Overall, six studies and 15 case reports have been published on HIT before or after heart, liver, kidney, and lung transplantation, respectively. The frequency of seroconversion for anti-PF4/heparin antibodies ranged between 1.9% and 57.9%. However, different methods to detect anti-PF4/heparin antibodies were applied. In none of the studies HIT-associated thromboembolic events or fatalities were observed. More importantly, in patients with a history of HIT, reexposure to heparin during transplantation was not associated with thrombotic complications. Taken together, the overall incidence of HIT after solid organ transplantation seems to be very low. However, according to the current knowledge, cardiac transplant recipients may have the highest risk to develop HIT. Different alternative suggestions for heparin-free anticoagulation have been reported for recipients with suspected HIT albeit no official recommendations on management have been published for this special collective so far.
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Heparin-induced thrombocytopenia(HIT) is a relatively infrequent complication of heparin administration. HIT can cause devastating thrombosis, making it one of the most serious adverse drug reactions encountered in clinical practice. We successfully treated a case of severe HIT presenting with thrombosis and life-threatening bleeding complications with intravenous immunoglobulin(IVIG), platelet transfusion and oral anticoagulant Rivaroxaban. In this case, we considered that IVIG played the most important role by preventing further thrombosis, increasing the platelet count, and ensuring the efficacy of Rivaroxaban. We therefore suggest that IVIG might be the optimal treatment for patients with this urgent condition.
基金supported by grant from the Ministry of Education of China(grant No.20110001120088)
文摘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.
文摘Objective: Acute pulmonary thromboembolism (PTE) is a serious high mortality pulmonary vascular disease whose effective treatment decreases morbidity and mortality. To determine if low-molecular-weight-heparin (LMWH) is clinically as efficient and safe as unfractionated heparin (UH) in patients with diagnosis of acute non-massive PTE, our study compares the efficacy, adverse effects and costs of LMWH and UH. Methods: One hundred and fourteen patients with non-massive acute PTE were randomly divided into LMWH (nadroparin calcium) and UH groups. Oxygenation index, D-dimer, fibrinogen (FG), lung ventilation/perfusion (V/Q) scan and computed tomography pulmonary angiography (CTPA) were observed before anticoagula-tion and on day 14 after anticoagulation. Results: In both groups, the ABG (arterial blood gas) analysis showed PaO2 and PaCO2 were elevated, P(A-a)O2 was decreased and oxygenation index (PaO2/FIO2) was elevated, D-dimer and fibrinogen were decreased, lung V/Q and CTPA showed embolized segments reduced (P<0.05). Hemorrhage and thrombocytopenia occurred in 3.5% of the LMWH group. Hemorrhage occurred in 5.3% and thrombocytopenia occurred in 7.0% of the UH group. The average cost in the LMWH group was RMB 1218.60 Yuan and RMB 1541.40 Yuan in the UH group. Conclusion: LMWH and UH are equally effective for treatment of non-massive acute PTE, but LMWH may have a lower prevalence of complications and is less expen-sive.
基金supported by the National Natural Science Foundation of China (Grant No.50732004)
文摘Biomedical molecule has received extensive application in surface modification coating.In this paper,polyethyleneimine （PEI）/heparin coating and chitosan/heparin coating on NiTi alloy substrates were prepared by layer-by-layer method,and differences of corrosion behavior and biocompatibility of the coatings were studied.Static contact angles and Fourier transform infrared （FT-IR） test were used to analysis the surface morphology and structure character of the materials,and atomic absorption spectrum was used to verify the corrosion behavior of the materials.Furthermore,hemolysis,dynamic clotting time and platelet binding test were utilized to investigate the biocompatibility of the materials.The results revealed that the blood compatibility of PEI/heparin coating is better than that of the chitosan/heparin coating as well as the substrate.
文摘Objective: To survey the effects of inhaled heparin on airway inflammation inguinea pigs with asthma and investigate the possible mechanism of inhaled heparin in the treatmentof asthma. Methods: The asthma in guinea pigs induced by ovalbumin was treated with inhaled heparin.The changes of cellularities in bronchoalveolar lavage (BAL) fluid and the airway walls wereexamined. Histologic examinations were also done in the guinea pig controls. Results: The number ofeosinophils, lymphocytes, and ciliated epithelial cells in the BAL fluid from the group treated withheparin was significantly lower than that of the group of asthma controls (P<0.01). Within theairway watts of the heparin treated group, the eosinophil infiltration was less prominent than thatof the group of asthma controls (P<0.001) and the number of mast cell was significantly higher thanthat of the group of asthma controls (P<0.01). Histologic examination showed that airway damages inthe heparin treated group were mild. Conclusion: Heparin can inhibit airway inflammation andalleviate airway damage in guinea pigs with asthma.
文摘Aim: The objective of this study is to review all the reported outcomes of heparin application in amniotic fluid embolism (AFE) so far and to find out why, when and how heparin or other anticoagulants should be used in AFE. Material and methods: We searched Medline (from 1969 to 2011), using two key words: 1) amniotic fluid embolism;2) amniotic fluid embolism and heparin. The search for the former produced 1127 replies, of which 208 were case reports of AFE. In response to the other key word, there were 94 articles. We looked through all the articles, selecting those relevant for our study. Results: In the years 1969-2011, 208 AFE cases were reported. Heparin (unfractionated heparin) or low molecular weight heparin (LMWH) was applied in 20 cases (9.6%), being the main drug in 11 cases (5.3%) and in 6 cases as a component of spectacular treatment of AFE (surgical treatment and extracorporal membrane oxygenation). In one of these cases anithrombin (AT) with LMWH was used. In one patient heparin therapy was considered to be unsuccessful and hence recombinant plasminogen activator (rt-PA) was instituted. All the patients survived. Conclusions: 1) The attempts to use heparin in AFE could be defined as promising, although the number of treated patients is too small for conclusion;2) The postulate to use heparin at the very onset of AFE (a bolus of 10,000 U followed by monitored intravenous infusion) has serious justification: one of the pathways of AFE is the target for heparin (coagulation pathway).
文摘Objective Heparin-induced thrombocytopenia(HIT)is a complication characterized by thrombocytopenia,hemorrhage and/or thrombosis,which is caused by initial or repeated application of unfractionated heparin(UFH)and low-molecular-weight heparin(LMWH).This study aims to summarize the clinical features of HIT in patients undergoing cardiac surgery.
文摘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.
文摘Heparin-induced thrombocytopenia (HIT) is a clinicopathologic syndrome because diagnosis is based on both clinical symptoms and laboratory data. We report a patient with multiple thromboembolic complications after daily flushing of intravenous line with small amounts of unfractionated heparin (UFH). At day 7 bilateral hemorrhagic infarction of the adrenal glands was misdiagnosed as adrenal adenoma. On day 10 thrombocytopenia was noted and the next day a myocardial infarction complicated by a left ventricular thrombus was diagnosed. On day 12, HIT was suspected. The pre-test probability for HIT according to the 4T-score was high (8/8 points) and detection of antibodies directed against the PF4/heparin-complex by particle gel immunoassay (Titer 1:1024) and ELISA (O.D. 2.784) was strongly positive. HIT can be induced by iv-line flushes with UFH. Arterial and venous thrombotic complications can be present before a clear platelet drop can be recognised.
文摘As one of the most commonly used anticoagulants, heparin plays an important role in the prevention and treatment of venous thrombosis. After many studies and demonstrations, we found that heparin mainly shows its biological activity by interacting with a variety of proteins. Heparins not only have anticoagulant effects, but also have good pharmacological effects in anti-tumor, anti-inflammatory, anti-virus, wound healing and anti anemia. On this basis, LMWH also has the advantages of good absorption, high bioavailability, long half-life, etc., so the clinical application of LMWH continues to expand. In recent years, there are many reports about low molecular weight heparin in the research work of heparin at home and abroad. This article mainly discusses the mechanism of action and clinical application of the above heparin drugs.
