Associations between coagulation factorⅫ,coagulation factorⅪ,and stability of venous thromboembolism:A case-control study

BACKGROUND Pulmonary embolism(PE)is a fatal clinical syndrome that is generally caused by an embolus from unstable deep venous thrombosis(DVT).However,clinical and biochemical factors that are related to the stability of DVT are not fully understood.AIM To evaluate the relationships between plasma antigen levels of factor XII(FXII:Ag)and factor XI(FXI:Ag)with the stability of DVT.METHODS Patients with DVT and no PE,DVT and PE,and controls with no DVT or PE that matched for age,gender,and comorbidities were included in this study.FXII:Ag and FXI:Ag in peripheral venous blood were measured using enzyme-linked immunosorbent assays.RESULTS Using the 95th percentile of FXI:Ag in patients with DVT and PE as the cut-off,a higher FXI:Ag was associated with a higher risk of unstable DVT(odds ratio:3.15,95%confidence interval:1.18-8.43,P=0.019).Stratified analyses showed consistent results in patients≤60 years(P=0.020),but not in those>60 years(P=0.346).CONCLUSION Higher plasma FXI:Ag might be a marker for unstable DVT,which might be associated with PE in these patients.

Prevention of thromboembolic events after radical prostatectomy in patients with hereditary thrombophilia due to a factor V Leiden mutation by multidisciplinary coagulation management

Objective:To examine the perioperative impact of factor V Leiden mutation on thromboembolic events'risk in radical prostatectomy(RP)patients.With an incidence of about 5%,factor V Leiden mutation is the most common hereditary hypercoagulability among Caucasians and rarer in Asia.The increased risk of thromboembolic events is three-to seven-fold in heterozygous and to 80-fold in homozygous patients.Methods:Within our prospectively collected database,we analysed 33006 prostate cancer patients treated with RP between December 2001 and December 2020.Of those,patients with factor V Leiden mutation were identified.All patients received individualised recommendation of haemostaseologists for perioperative anticoagulation.Thromboembolic complications(deep vein thrombosis and pulmonary embolism)were assessed during hospital stay,as well as according to patient reported outcomes within the first 3 months after RP.Results:Overall,85(0.3%)patients with known factor V Leiden mutation were identified.Median age was 65(interquartile range:61-68)years.There was at least one thrombosis in 53(62.4%)patients and 31(36.5%)patients had at least one embolic event in their medical history before RP.Within all 85 patients with factor V Leiden mutation,we experienced no thromboembolic complications within the first 3 months after surgery.Conclusion:In our cohort of patients with factor V Leiden mutation,no thromboembolic events were observed after RP with an individualised perioperative coagulation management concept.This may reassure patients with this hereditary condition who are counselled for RP.

Anti-vascular endothelial growth factor drugs combined with laser photocoagulation maintain retinal ganglion cell integrity in patients with diabetic macular edema: study protocol for a prospective, non-randomized, controlled clinical trial

The integrity of retinal ganglion cells is tightly associated with diabetic macular degeneration that leads to damage and death of retinal ganglion cells,affecting vision.The major clinical treatments for diabetic macular edema are anti-vascular endothelial growth factor drugs and laser photocoagulation.However,although the macular thickness can be normalized with each of these two therapies used alone,the vision does not improve in many patients.This might result from the incomplete recovery of retinal ganglion cell injury.Therefore,a prospective,non-randomized,controlled clinical trial was designed to investigate the effect of anti-vascular endothelial growth factor drugs combined with laser photocoagulation on the integrity of retinal ganglion cells in patients with diabetic macular edema and its relationship with vision recovery.In this trial,150 patients with diabetic macular edema will be equally divided into three groups according to therapeutic methods,followed by treatment with anti-vascular endothelial growth factor drugs,laser photocoagulation therapy,and their combination.All patients will be followed up for 12 months.The primary outcome measure is retinal ganglion cell-inner plexiform layer thickness at 12 months after treatment.The secondary outcome measures include retinal ganglion cell-inner plexiform layer thickness before and 1,3,6,and 9 months after treatment,retinal nerve fiber layer thickness,best-corrected visual acuity,macular area thickness,and choroidal thickness before and 1,3,6,9,and 12 months after treatment.Safety measure is the incidence of adverse events at 1,3,6,9,and 12 months after treatment.The study protocol hopes to validate the better efficacy and safety of the combined treatment in patients with diabetic macula compared with the other two monotherapies alone during the 12-month follow-up period.The trial is designed to focus on clarifying the time-effect relationship between imaging measures related to the integrity of retinal ganglion cells and best-corrected visual acuity.The trial protocol was approved by the Medical Ethics Committee of the Affiliated Hospital of Beihua University with approval No.(2023)(26)on April 25,2023,and was registered with the Chinese Clinical Trial Registry(registration number:ChiCTR2300072478,June 14,2023,protocol version:2.0).

Comparison between sepsis-induced coagulopathy and sepsis-associated coagulopathy criteria in identifying sepsis-associated disseminated intravascular coagulation

BACKGROUND:Disseminated intravascular coagulation(DIC)is associated with increased mortality in sepsis patients.In this study,we aimed to assess the clinical ability of sepsis-induced coagulopathy(SIC)and sepsis-associated coagulopathy(SAC)criteria in identifying overt-DIC and preDIC status in sepsis patients.METHODS:Data from 419 sepsis patients were retrospectively collected from July 2018 to December 2022.The performances of the SIC and SAC were assessed to identify overt-DIC on days 1,3,7,or 14.The SIC status or SIC score on day 1,the SAC status or SAC score on day 1,and the sum of the SIC or SAC scores on days 1 and 3 were compared in terms of their ability to identify pre-DIC.The SIC or SAC status on day 1 was evaluated as a pre-DIC indicator for anticoagulant initiation.RESULTS:On day 1,the incidences of coagulopathy according to overt-DIC,SIC and SAC criteria were 11.7%,22.0%and 31.5%,respectively.The specificity of SIC for identifying overt-DIC was significantly higher than that of the SAC criteria from day 1 to day 14(P<0.05).On day 1,the SIC score with a cut-off value>3 had a significantly higher sensitivity(72.00%)and area under the curve(AUC)(0.69)in identifying pre-DIC than did the SIC or SAC status(sensitivity:SIC status 44.00%,SAC status 52.00%;AUC:SIC status 0.62,SAC status 0.61).The sum of the SIC scores on days 1 and 3 had a higher AUC value for identifying the pre-DIC state than that of SAC(0.79 vs.0.69,P<0.001).Favorable effects of anticoagulant therapy were observed in SIC(adjusted hazard ratio[HR]=0.216,95%confidence interval[95%CI]:0.060–0.783,P=0.018)and SAC(adjusted HR=0.146,95%CI:0.041–0.513,P=0.003).CONCLUSION:The SIC and SAC seem to be valuable for predicting overt-DIC.The sum of SIC scores on days 1 and 3 has the potential to help identify pre-DIC.

Effects of Coagulation and Ozonation Pretreatments on Biochemical Treatment of Fluid Catalytic Cracking Wastewater

Fluid catalytic cracking (FCC) salty wastewaters, containing quaternary ammonium compounds (QACs), are very difficult to treat by biochemical process. Anoxic/oxic (A/O) biochemical system, based on nitrification and denitrification reactions, was used to assess their possible biodegradation. Because of the negative effects of high salt concentration (3%), heavy metals and toxic organic matter on microorganisms’ activities, some techniques consisting of dilution, coagulation and flocculation, and ozonation pretreatments, were gradually tested to evaluate chemical oxygen demand (COD), ammonia-nitrogen (ammonia-N) and total nitrogen (TN) removal rates. In this process of FCC wastewater, starting with university-domesticated sludge, the ammonia-N and TN removal rates were worst. However, when using domesticated SBR’s sludge and operating with five-fold daily diluted influent (thus reducing salt concentration), the ammonia-N removal reached about 57% while the TN removal rate was less than 37% meaning an amelioration of the nitrification process. However, by reducing the dilution factors, these results were inflected after some days of operation, with ammonia-N removal decreasing and TN barely removed meaning a poor nitrification. Even by reducing heavy metals concentration with coagulation/flocculation process, the results never changed. Thereafter, by using ozonation pre-treatment to degrade the detected organic matter of di-tert-butylphenol and certain isoparaffins, COD, ammonia-N and TN removal rates reached 92%, 62% and 61%, respectively. These results showed that the activities of the microorganisms were increased, thus indicating a net denitrification and nitrification reactions improvement.

Expression and Purification of Human Coagulation Factor X in Mammalian CHO-DG44 Cells

[Objectives]This study was conducted to obtain a Chinese hamster ovary cell line that stably expresses recombinant human coagulation factor X(rhFX),and to induce efficient expression of the target gene with different concentrations of methotrexate(MTX).[Methods]PCR was performed to obtain the rhFX gene,and a recombinant expression plasmid pOptiVEC-rhFX was constructed and subjected to double restriction endonuclease digestion and sequencing identification.CHO-DG44(DHFR-)cells were transfected by the liposome method,and the target protein was purified by affinity chromatography and detected by SDS-PAGE electrophoresis and Western blot.A cell line with efficient and stable expression of the target gene was obtained by increasing the concentration of MTX to select positive clones.[Results]PCR yielded a 1509 bp rhFX sequence,and the results of double digestion and sequencing showed that the constructed pOptiVEC-rhFX plasmid was correct.After transfection of cells,MTX significantly increased protein expression.When MTX reached 1.0μmol/L,the expression efficiency of the target protein was(9±0.27)μg/ml.The purity of the target protein purified by affinity chromatography was 93%,which could be used for subsequent experiments.The expression efficiency of rhFX in eukaryotic mammalian cells was improved by increasing MTX concentration,and an affinity chromatography purification process for the target protein was preliminarily established.[Conclusions]The results of this study provide data support for the expression and purification of rhFX,and will lay a solid foundation for the development of drugs related to rhFX.

Coagulation abnormalities and their relationship with bleeding manifestations in patients with dengue-A single center observational study

Objective:To evaluate coagulation abnormalities and their relationship with bleeding manifestations among patients with dengue.Methods:This observational study was conducted on 292 adult dengue patients who were admitted to a tertiary care hospital of Western India from July 2021 to June 2022.Coagulation tests including prothrombin time(PT),international normalized ratio(INR),activated partial thromboplastin time(aPTT),fibrinogen,and D-dimer were performed.Patients were monitored for bleeding manifestations.Results:Coagulation abnormalities were reported in 42.8%of the patients.Overall,prolonged aPTT was the most common coagulation abnormality(40.8%),followed by low fibrinogen(38.7%),raised D-dimer(31.2%),raised INR(26.0%)and prolonged PT(19.2%).Bleeding manifestations were present in 19.9%patients.PT,INR,aPTT and D-dimer levels were significantly higher(P<0.01)and fibrinogen level was significantly lower(P<0.001)in patients with bleeding compared to patients without bleeding.Patients with bleeding had a significantly higher rate of all coagulation abnormalities than patients without bleeding(P<0.01).Conclusions:Patients with bleeding showed a significantly higher frequency of coagulation abnormalities compared to patients without bleeding.Patients with dengue should be assessed for coagulation abnormalities.

Binding of EGF1 Domain Peptide in Coagulation Factor Ⅶ with Tissue Factor and Its Implications for the Triggering of Coagulation

The binding function of EGF1 domain peptide with tissue factor(TF)and its ability of triggering coagulation were explored.The TF expression model in vitro was established by lipopolysaccha-ride induction.The affinity of EGFP-EGF1 and TF expressing cells was analyzed by fluorescence microscopy and flow cytometry(FCM).The affinity of EGFP-EGF1 and rat soluble TF was quantitated by surface plasmon resonance(SPR).The ability of EGFP-EGF1 in triggering coagulation was tested by prothrombin time assay.The FCM res...

Preparation and Structure of a New Coagulation Factor XI Catalytic Domain for Drug Discovery

Human blood coagulation factor XI （FXI） is a key enzyme in the amplification phase of blood coagulation cascade, and is recognized as an important target for anti-coagulant development in recent years. We designed a new mutant form of FXIa catalytic domain rhFXI370-607 （N73Q-N113Q-C123S）, and report here the facile preparation, protein crystallization, and crystal structure of this protein. We highlight a few unique structural features of FXIa after comparison with the trypsin family serine proteases at sequence and structural levels. This work provides a foundation to develop new small molecular FXIa inhibitors with increased potency and specificity.

Diagnostic and Prognostic Value of Plasma Factor V Activity and Parameters in Thrombin Generation for Disseminated Intravascular Coagulation in Patients with Hematological Malignancies

In this study,we used plasma factor V activity and parameters of the thrombin generation test to discuss their diagnostic and prognostic value for disseminated intravascular coagulation (DIC) in patients with hematological malignancies.A total of 164 patients who were diagnosed with hematological malignancies in the Department of Hematology,Union Hospital,between Apr 2014 and Dec.2014 were enrolled in this study.There were 131 patients in the study group and 33 patients in the control group in terms of the laboratory results for DIC.The patients in the study group were divided into a DIC subgroup (n=59) and a non-DIC subgroup (n=72) based on the International Society of Thrombosis and Hemostasis (ISTH) Integral System,and they were divided into four subgroups [score ≤3 (n=35),score=4 (n=37),score=5 (n=47),and score >6 (n=12)] according to ISTH scores.Using 28-day mortality as the endpoint,the patients in the study group were divided into a survival subgroup (n=111) and a non-survival subgroup (n=20).The results showed that the plasma factor V activity was significantly weaker,and lag time and time to peak were significantly shorter in the study group than in the control group (P<0.01).The factor V activity,peak and endogenous thrombin potential (ETP) were significantly decreased in the DIC subgroup as compared with those in the non-DIC subgroup (P<0.01).Among factor V activity,lag time,peak,ETP,and ttPeak,only the factor V activity was significantly decreased in the nonsurvival subgroup compared with the survival subgroup (P<0.01).With the increase in ISTH score,the ETP and peak decreased gradually.The binary logistic regression analysis revealed that PLT,D-dimer,factor V activity and ETP had linear relationship with DIC diagnosed by ISTH Integral System.Using DIC diagnosed by ISTH Integral System as the endpoint,the area under curve (AUC) of factor V activity was found to be similar to that of blood platelet count (PLT) and prothrombin time (PT).In conclusion,factor V activity,ETP and peak had diagnostic value for DIC in patients with hematological malignancies,and only factor V activity had limited prognostic value.

Influences of dexmedetomidine on stress responses and postoperative cognitive and coagulation functions in patients undergoing radical gastrectomy under general anesthesia

BACKGROUND Radical gastrectomy(RG)is commonly used in the treatment of patients with gastric cancer(GC),but this procedure may lead to stress responses,postoperative cognitive dysfunction,and blood coagulation abnormalities in patients.AIM To investigate the influences of dexmedetomidine(DEX)on stress responses and postoperative cognitive and coagulation functions in patients undergoing RG under general anesthesia(GA).METHODS One hundred and two patients undergoing RG for GC under GA from February 2020 to February 2022 were retrospectively reviewed.Of these,50 patients had received conventional anesthesia intervention[control group(CG)]and 52 patients had received DEX in addition to routine anesthesia intervention[observation group(OG)].Inflammatory factor(IFs;tumor necrosis factor-α,TNF-α;interleukin-6,IL-6),stress responses(cortisol,Cor;adrenocorticotropic hormone,ACTH),cognitive function(CF;Mini-Mental State Examination,MMSE),neurological function(neuron-specific enolase,NSE;S100 calciumbinding protein B,S100B),and coagulation function(prothrombin time,PT;thromboxane B2,TXB2;fibrinogen,FIB)were compared between the two groups before surgery(T0),as well as at 6 h(T1)and 24 h(T2)after surgery.RESULTS Compared with T0,TNF-α,IL-6,Cor,ACTH,NSE,S100B,PT,TXB2,and FIB showed a significant increase in both groups at T1 and T2,but with even lower levels in OG vs CG.Both groups showed a significant reduction in the MMSE score at T1 and T2 compared with T0,but the MMSE score was notably higher in OG compared with CG.CONCLUSION In addition to a potent inhibitory effect on postoperative IFs and stress responses in GC patients undergoing RG under GA,DEX may also alleviate the coagulation dysfunction and improve the postoperative CF of these patients.

High-yield expression of recombinant mouse coagulation factor Ⅶ in methylotrophic yeast Pichia pastoris

Objective: To explore high-yield secretory expression of recombinant mouse coagulation factor Ⅶ (rmF Ⅶ ) protein in Pichia pastoris (P. pastoris). Methods: The fragment of mF Ⅶ cDNA was amplified by PCR from a pcDNA3-mFⅦ plasmid. Then the cDNA fragment was subcloned into α-factor secretion signal open reading frame of pPIC9K secretory expression vector. The mutagenesis of mF Ⅶ was performed by Site-Direct Mutation and then verified by DNA sequencing. The yeast expression vector of rmF Ⅶ, named as pPIC9K-rmFⅦ, was linearized with Sac I and transferred into GS115 strains(his-Mut+)by electroporation. The recombinants were identified by direct PCR and selection on MM and MD plates. rmF Ⅶ was expressed in recombinant strains (his+Mut+) for 4 d. The expression level and activation of rmF Ⅶ in the BMMY medium were detected by SDS-PAGE and Western blot respectively. Results:pPIC9K-rmFⅦ was constructed and transferred to GS115 strains successfully. 48-hour post induction by methanol rmFⅦ protein was secreted into the culture supernatant. The molecular weight of the expressed products was shown to be about 46 kD by SDS-PAGE analysis. Western blot showed that the expressed rmF Ⅶ exhibited specificity and antigenicity. Conclusion: Since mFⅦ is considered as a tumor-targeting molecule , this study may provide a basis for further anti-tumor strategy on rmFⅦ.

Clinical association between coagulation indicators and bone metastasis in patients with gastric cancer

BACKGROUND Bones are one of the most common target organs for cancer metastasis.Early evaluation of bone metastasis(BM)status is clinically significant.Cancer patients often experience a hypercoagulable state.AIM To evaluate the correlation between coagulation indicators and the burden of BM in gastric cancer(GC).METHODS We conducted a single-center retrospective study and enrolled 454 patients.Clinical information including routine blood examination and coagulation markers were collected before any treatment.Patients were grouped according to the status of BM.Receiver operating characteristic curves were used to assess diagnostic performance and determine the optimal cutoff values of the above indicators.Cutoff values,sensitivity and specificity were based on the maximum Youden index.Univariate and multivariate logistic regression analyses were used to evaluate the relationships between biomarkers and BM.RESULTS Of the 454 enrolled patients,191 patients were diagnosed with BM.The receiver operating characteristic curve analysis suggested that prothrombin time(PT)Wang X et al.Coagulation indicators predict bone metastasis WJGO https://www.wjgnet.com 1254 July 15,2023 Volume 15 Issue 7[cutoff:13.25;sensitivity:0.651;specificity:0.709;area under receiver operating characteristic curve(AUC)=0.738],activated partial thromboplastin time(aPTT)(cutoff:35.15;sensitivity:0.640;specificity:0.640;AUC=0.678)and fibrin degradation products(FDP)(cutoff:2.75;sensitivity:0.668;specificity:0.801;AUC=0.768)act as novel predictors for BM.Based on multivariate logistic regression analysis,the results showed the independent correlation between PT[odds ratio(OR):3.16;95%confidence interval(CI):1.612-6.194;P=0.001],aPTT(OR:2.234;95%CI:1.157-4.313;P=0.017)and FDP(OR:3.17;95%CI:1.637-6.139;P=0.001)and BM in patients with GC.Moreover,age,carcinoembryonic antigen,erythrocyte and globulin were found to be significantly associated with BM.CONCLUSION Coagulation markers,namely PT,aPTT and FDP,might be potential predictors for screening BM in patients with GC.

Investigating the Performance of the Coagulation Process When Using a Combination of Zinc Oxide Nanoparticles and Ferric Polysulfate

In this article, a new type of coagulant material has been investigated and the performance of the coagulation process using this type of coagulant was evaluated. This new type is a combination of zinc oxide nanoparticles and polyferric sulfate (ZnOPFS). The structure of zinc oxide nanoparticles was determined by spectroscopic, X-ray and electron microscopy methods, and based on this, it was determined that ZnOPFS is a complex and mixed compound that is mainly composed of zinc oxide nanoparticles and ferric sulfate. The effects of Zn/Fe (Zn/Fe) molar ratio and aging (time) on acidity and zeta potential were also evaluated using a specific method. The obtained results showed that in the simultaneous deposition process, zinc ions can prevent the formation of polyferric acid coagulation and subsequently improve the stability of ZnOPFS.

Expression of tissue factor in pancreatic adenocarcinoma is associated with activation of coagulation

瞄准：在 thromboembolism 的开发在胰腺的癌症和它的角色学习织物因素(TF ) 的表示。方法：TF 表示被北污点和间接免疫荧光在八根人的胰腺的癌房间线学习。或者拼接的 TF (asTF ) 的表示被 RT-PCR 估计。另外， TF 表示被免疫荧光与胰腺的腺癌(PCa ) 在 19 个病人的胰腺的纸巾决定，有慢性胰炎(CP ) 的 9 个病人和 20 正常控制。血浆样品(30 PCa 病人， 13 CP 病人和 20 控制) 为可溶的 TF 层次和凝结激活标记被调查[thrombin-antithrombin III 建筑群(梭织) ，凝血素碎片 1 + 2 (F1 + 2 )] 。结果：所有胰腺的癌房间线表示了 TF (8/8 ) ，他们中的大多数表示了 asTF (6/8 ) 。在蛋白质水平的 TF 表示没与癌房间线的区别相关。几乎，二件胰腺的癌症组织样品染色了为 TF (17/19 ) 积极。在 CP 的所有样品，弱染色被限制为胰腺的管房间，而一些仅仅内皮下房间在正常控制的 9/20 是积极的。TF 并且在 PCa 病人梭织层次而 2 铺平的提高的 F1 + 没与控制相比到达统计意义，显著地与控制相比被提高。在病人们梭织的 CP 和 F1 + ， 2 个层次证明了显著地与控制相比被提高，尽管梭织举起少些比在 PCa 病人被读。结论：我们结束那除了起来房间膜上的 TF 的调整表示，可溶的 TF 可能在胰腺的癌症贡献凝结系统的激活。

In silico evidence of Remdesivir action in blood coagulation cascade modulation in COVID-19 treatment

BACKGROUND Coronavirus disease 2019(COVID-19)has demonstrated several clinical manifestations which include not only respiratory system issues but also liver,kidney,and other organ injuries.One of these abnormalities is coagulopathies,including thrombosis and disseminated intravascular coagulation.Because of this,the administration of low molecular weight heparin is required for patients that need to be hospitalized.In addition,Remdesivir is an antiviral that was used against Middle East Acute Respiratory Syndrome,Ebola,Acute Respiratory Syndrome,and other diseases,showing satisfactory results on recovery.Besides,there is evidence suggesting that this medication can provide a better prognosis for patients with COVID-19.AIM To investigate in silico the interaction between Remdesivir and clotting factors,pursuing a possibility of using it as medicine.METHODS In this in silico study,the 3D structures of angiotensin-converting enzyme 2(ACE2),Factor I(fibrinogen),Factor II(prothrombin),Factor III(thromboplastin),Factor V(proaccelerin),Factor VII(proconvertin),Factor VIII(antihemophilic factor A),Factor IX(antihemophilic factor B),Factor X(Stuart-Prower factor),and Factor XI(precursor of thromboplastin(these structures are technically called receptors)were selected from the Protein Data Bank.The structures of the antivirals Remdesivir and Osetalmivir(these structures are called ligands)were selected from the PubChem database,while the structure of Atazanavir was selected from the ZINC database.The software AutoDock Tools(ADT)was used to prepare the receptors for molecular docking.Ions,peptides,water molecules,and other ones were removed from each ligand,and then,hydrogen atoms were added to the structures.The grid box was delimited and calculated using the same software ADT.A physiological environment with pH 7.4 is needed to make the ligands interact with the receptors,and still the software Marvin sketch®(ChemAxon®)was used to forecast the protonation state.To perform molecular docking,ADT and Vina software was connected.Using PyMol®software and Discovery studio®software from BIOVIA,it was possible to analyze the amino acid residues from receptors that were involved in the interactions with the ligands.Ligand tortions,atoms that participated in the interactions,and the type,strength,and duration of the interactions were also analyzed using those software.RESULTS Molecular docking analysis showed that Remdesivir and ACE2 had an affinity energy of-8.8 kcal/moL,forming a complex with eight hydrogen bonds involving seven atoms of Remdesivir and five amino acid residues of ACE2.Remdesivir and prothrombin had an interaction with six hydrogen bonds involving atoms of the drug and five amino acid residues of the clotting factor.Similar to that,Remdesivir and thromboplastin presented interactions via seven hydrogen bonds involving five atoms of the drug and four residues of the clotting factor.While Remdesivir and Factor V established a complex with seven hydrogen bonds between six antiviral atoms and six amino acid residues from the factor,and Factor VII connected with the drug by four hydrogen bonds,which involved three atoms of the drug and three residues of amino acids of the factor.The complex between Remdesivir and Factor IX formed an interaction via 11 hydrophilic bonds with seven atoms of the drug and seven residues of the clotting factor,plus one electrostatic bond and three hydrophobic interactions.Factor X and Remdesivir had an affinity energy of-9.6 kcal/moL,and the complex presented 10 hydrogen bonds and 14 different hydrophobic interactions which involved nine atoms of the drug and 16 amino acid residues of the clotting factor.The interaction between Remdesivir and Factor XI formed five hydrogen bonds involving five amino acid residues of the clotting factor and five of the antiviral atoms.CONCLUSION Because of the in silico significant affinity,Remdesivir possibly could act in the severe acute respiratory syndrome coronavirus 2 infection blockade by interacting with ACE2 and concomitantly act in the modulation of the coagulation cascade preventing the hypercoagulable state.

Virus Removal by Iron Coagulation Processes

Waterborne viruses account for 30% to 40% of infectious diarrhea, and some viruses could persevere for some months in nature and move up to 100 m in groundwater. Using filtration setups, coagulation could lessen virus charges as an efficient pre-treatment for reducing viruses. This work discusses the present-day studies on virus mitigation using coagulation in its three versions i.e., chemical coagulation (CC), enhanced coagulation, and electrocoagulation (EC), and debates the new results of virus demobilization. The complexity of viruses as bioparticles and the process of virus demobilization should be adopted, even if the contribution of permeability in virus sorption and aggregation needs to be clarified. The information about virion permeability has been evaluated by interpreting empirical electrophoretic mobility (EM). No practical measures of virion permeability exist, a clear link between permeability and virion composition and morphology has not been advanced, and the direct influence of inner virion structures on surface charge or sorption has yet to be conclusively demonstrated. CC setups utilizing zero-valent or ferrous iron could be killed by iron oxidation, possibly using EC and electrooxidation (EO) methods. The oxidants evolution in the iron oxidation method has depicted promising findings in demobilizing bacteriophage MS2, even if follow-up investigations employing an elution method are needed to secure that bacteriophage elimination is related to demobilization rather than sorption. As a perspective, we could be apt to anticipate virus conduct and determine new bacteriophage surrogates following subtle aspects such as protein structures or genome size and conformation. The present discussion’s advantages would extend far beyond an application in CC—from filtration setups to demobilization by nanoparticles to modeling virus fate and persistence in nature.

Perioperative coagulation activation after permanent pacemaker placement

BACKGROUND Bradyarrhythmias are typically treated with permanent pacemakers(PM). The elimination of bradyarrhythmia by PM implantation improves the patient’s quality of life and prognosis, but it can also result in a number of sequalae. It is still unclear how PM implantation affects the hemostasis system’s parameters and how such parameters relate to different consequences after PM placement.AIM To assess the blood coagulation factor activity in PM patients throughout the perioperative period.METHODS Patients treated in the Department of Surgical Therapy of Cardiac Arrhythmias and Pacing at the Ryazan State "Regional Clinical Cardiology Dispensary" from April 2020 to December 2021 were included in the study. Before surgery, 7 and 30 d after PM placement, peripheral venous blood samples were withdrawn to measure the level of blood coagulation factor Ⅰ(FⅠ) and the activity of blood coagulation factors Ⅱ(FⅡ), Ⅴ(FⅤ), Ⅶ(FⅦ), Ⅷ(FⅧ), ⅸ(Fⅸ), ⅹ(Fⅹ), Ⅺ(FⅪ), Ⅻ(FⅫ). We used an automatic coagulometer Sysmex CA 660(Sysmex Europe, Germany) and reagents from Siemens(Siemens Healthcare Diagnostics Products GmbH, Germany).RESULTS The study included 146 patients. The activity of factors FⅤ [147.7(102.1-247.55)% vs 103.85(60-161.6)% vs 81.8(67.15-130.65)%, P = 0.002], FⅧ [80.4(60.15-106.25)% vs 70.3(48.5-89.1)% vs 63.7(41.6-88.25)%, P = 0.039], Fⅸ [86.2(70.75-102.95)% vs 75.4(59.2-88.3)% vs 73.9(56.45-93.05)%, P = 0.014], Fⅹ [188.9(99.3-308.18)% vs 158.9(83.3-230)% vs 127.2(95.25-209.35)%, P = 0.022], FⅪ [82.6(63.9-103.6)% vs 69.75(53.8-97.6)% vs 67.3(54.25-98.05)%, P = 0.002], FⅫ [87.6(67.15-102.3)% vs 78.9(63.4-97.05)% vs 81.2(62.15-97.4)%, P < 0.001] decreased at 7 and 30 d after surgery;FⅡ activity [157.9(109.7-245.25)% vs 130(86.8-192.5)% vs 144.8(103.31-185.6)%, P = 0.021] decreased at 7 d and increased at 30 d postoperatively. There were no statistically significant changes in the FVII activity within 30 d after PM placement [182.2(85.1-344.8)% vs 157.2(99.1-259)% vs 108.9(74.9-219.8)%, P = 0.128]. Subgroup analysis revealed similar changes only in patients on anticoagulant therapy. FⅫ activity decreased in patients on antiplatelet therapy [82(65.8-101.9)% vs 79.9(63.3-97.1)% vs 89.7(75.7-102.5)%, P = 0.01] 7 d after surgery, returning to baseline values at 30 d postoperatively.CONCLUSION PM placement and anticoagulant therapy were associated with decreased activity of clotting factors FⅤ, FⅧ, Fⅸ, Fⅹ, FⅪ, FⅫ in the postoperative period. FⅧ activity did not decrease within 30 d after PM placement, which may indicate endothelial injury caused by lead placement.

The Effect of Lanthanide and Transition Metal Ions on the Fluorescence Spectra for the Anticoagulation Factor of Snake Venom

The effect of lanthanide and transition metal ions on the fluorescence spectra of the anticoagulation factor(ACF)of snake venom has been studied.It is postulated that the quenching of tryptophan residue fluorescence by lanthanide and transition metal ions is caused by the metal ion-induced conformation change of ACF.

Significant risk factors for intensive care unit-acquired weakness:A processing strategy based on repeated machine learning

BACKGROUND Intensive care unit-acquired weakness(ICU-AW)is a common complication that significantly impacts the patient's recovery process,even leading to adverse outcomes.Currently,there is a lack of effective preventive measures.AIM To identify significant risk factors for ICU-AW through iterative machine learning techniques and offer recommendations for its prevention and treatment.METHODS Patients were categorized into ICU-AW and non-ICU-AW groups on the 14th day post-ICU admission.Relevant data from the initial 14 d of ICU stay,such as age,comorbidities,sedative dosage,vasopressor dosage,duration of mechanical ventilation,length of ICU stay,and rehabilitation therapy,were gathered.The relationships between these variables and ICU-AW were examined.Utilizing iterative machine learning techniques,a multilayer perceptron neural network model was developed,and its predictive performance for ICU-AW was assessed using the receiver operating characteristic curve.RESULTS Within the ICU-AW group,age,duration of mechanical ventilation,lorazepam dosage,adrenaline dosage,and length of ICU stay were significantly higher than in the non-ICU-AW group.Additionally,sepsis,multiple organ dysfunction syndrome,hypoalbuminemia,acute heart failure,respiratory failure,acute kidney injury,anemia,stress-related gastrointestinal bleeding,shock,hypertension,coronary artery disease,malignant tumors,and rehabilitation therapy ratios were significantly higher in the ICU-AW group,demonstrating statistical significance.The most influential factors contributing to ICU-AW were identified as the length of ICU stay(100.0%)and the duration of mechanical ventilation(54.9%).The neural network model predicted ICU-AW with an area under the curve of 0.941,sensitivity of 92.2%,and specificity of 82.7%.CONCLUSION The main factors influencing ICU-AW are the length of ICU stay and the duration of mechanical ventilation.A primary preventive strategy,when feasible,involves minimizing both ICU stay and mechanical ventilation duration.