Platelet indices(PIs)including high mean platelet volume(MPV),plateletcrit(PLC),and platelet distribution width(PLDW)are associated with poor glycemic control.In addition,they can indicate prothrombotic and procoagula...Platelet indices(PIs)including high mean platelet volume(MPV),plateletcrit(PLC),and platelet distribution width(PLDW)are associated with poor glycemic control.In addition,they can indicate prothrombotic and procoagulation risk among patients with diabetes.PI measurement is cheap,quick and fits healthcare system needs in remote outreaching areas in low-income countries.However,a broader insight into their clinical implications in diabetes is lacking.To achieve a wider understanding,we reviewed PubMed/MEDLINE,Google Scholar and Cochrane Library for relevant articles investigating the role of PIs in diabetes mellitus.No limitation to the publication date was applied,which included all articles published up to August 17,2024.The terms used were MPV,PLC,PLDW,platelet large cell ratio,glycated hemoglobin(HbA1c),PIs,platelet activity and diabetes mellitus.Out of the 790 articles retrieved,187 full texts were reviewed,and 44 were included.PIs,when measurements are done promptly and within 2 h,could be short-term pointers to glycemic control in the life span of the platelets(2 wk).PIs are easy to perform,cheap and useful in remote outreaching areas with limited facilities where measurement of HbA1c is not available or cost-effective.However,PIs are not specific and are affected by demographic factors,such as pregnancy,renal failure,medications,hemoglobin and duration of diabetes.PIs could be implemented with daily blood glucose to inform doctors in low-income countries about their patients'glycemic control and cardiovascular risk.An important application might be when blood glucose control is needed quickly(before elective surgery).展开更多
Crimean-Congo hemorrhagic fever(CCHF)is a hemorrhagic fever caused by infection with the CCHF virus(CCHFV)and has a mortality rate of up to 30%.Thrombocytopenia is a hallmark of CCHF;however,the mechanisms underlying ...Crimean-Congo hemorrhagic fever(CCHF)is a hemorrhagic fever caused by infection with the CCHF virus(CCHFV)and has a mortality rate of up to 30%.Thrombocytopenia is a hallmark of CCHF;however,the mechanisms underlying this manifestation remain poorly understood.In addition to hemostasis,platelets play a crucial role in recognizing pathogens and mediating immune responses.We investigated the mechanisms underlying thrombocytopenia associated with CCHFV infection by analyzing the platelet transcriptome in mice.Interferon-induced transmembrane protein 3(IFITM3),a known antiviral factor,was significantly upregulated.The role of IFITM3 in response to CCHFV infection was characterized using the human megakaryoblast cell line MEG-01,considered a parental cell line of platelets.Although the CCHFV infection rate was limited,MEG-01 cells maintained the infection and replication of CCHFV,leading to increased IFITM3 protein expression.We demonstrated that IFITM3 overexpression efficiently inhibited CCHFV infection,whereas IFITM3 knockout promoted viral infection.An interaction between IFITM3 and the CCHFV glycoprotein Gc was identified,which suppressed CCHFV entry into cells.The IFITM3 CIL-TMD domain is critical for this interaction.These results suggest that IFITM3 is a restriction factor and plays an antiviral role during CCHFV infection.Elevated expression of IFITM3 in platelets indicates that this could be a common mechanism by which platelets protect against viruses,including CCHFV,which may reduce platelet consumption and destruction caused by CCHFV infection.These findings provide valuable insights into the pathogenesis of CCHF-associated thrombocytopenia and offer foundational theoretical support for future therapeutic strategies.展开更多
Background:The essential roles of platelets in thrombosis have been well recognized.Unexpectedly,thrombosis is prevalent during thrombocytopenia induced by cytotoxicity of biological,physical and chemical origins,whic...Background:The essential roles of platelets in thrombosis have been well recognized.Unexpectedly,thrombosis is prevalent during thrombocytopenia induced by cytotoxicity of biological,physical and chemical origins,which could be suffered by military personnel and civilians during chemical,biological,radioactive,and nuclear events.Especially,thrombosis is considered a major cause of mortality from radiation injury-induced thrombocytopenia,while the underlying pathogenic mechanism remains elusive.Methods:A mouse model of radiation injury-induced thrombocytopenia was built by exposing mice to a sublethal dose of ionizing radiation(IR).The phenotypic and functional changes of platelets and megakaryocytes(MKs)were determined by a comprehensive set of in vitro and in vivo assays,including flow cytometry,flow chamber,histopathology,Western blotting,and chromatin immunoprecipitation,in combination with transcriptomic analysis.The molecular mechanism was investigated both in vitro and in vivo,and was consolidated using MK-specific knockout mice.The translational potential was evaluated using a human MK cell line and several pharmacological inhibitors.Results:In contrast to primitive MKs,mature MKs(mMKs)are intrinsically programmed to be apoptosis-resistant through reprogramming the Bcl-xL-BAX/BAK axis.Interestingly,mMKs undergo minority mitochondrial outer membrane permeabilization(MOMP)post IR,resulting in the activation of the cyclic GMP-AMP synthase-stimulator of IFN genes(cGAS-STING)pathway via the release of mitochondrial DNA.The subsequent interferon-β(IFN-β)response in mMKs upregulates a GTPase guanylate-binding protein 2(GBP2)to produce large and hyperreactive platelets that favor thrombosis.Further,we unmask that autophagy restrains minority MOMP in mMKs post IR.Conclusions:Our study identifies that megakaryocytic mitochondria-cGAS/STING-IFN-β-GBP2 axis serves as a fundamental checkpoint that instructs the size and function of platelets upon radiation injury and can be harnessed to treat platelet pathologies.展开更多
This letter critically evaluates Jiang et al's article on the differentiation of benign and malignant liver lesions using Emax and platelet count.Despite notable findings,significant methodological and interpretat...This letter critically evaluates Jiang et al's article on the differentiation of benign and malignant liver lesions using Emax and platelet count.Despite notable findings,significant methodological and interpretative limitations are identified.The study lacks detailed assay conditions for Emax measurement,employs inadequate statistical methods without robust multivariate analysis,and does not provide clinically relevant threshold values.The nomogram's reliance on Emax as a major diagnostic contributor is questionable due to attenuation in hepatocellular carcinoma patients with cirrhosis.Moreover,the study's limitations,such as selection bias and confounding factors,are not adequately addressed.Future research should adopt more rigorous methodologies,including prospective studies with larger cohorts and standardized protocols for biomarker measurement,to enhance validity and clinical applicability.展开更多
In this editorial,we discuss the recent article by Regassa et al,published in the World Journal of Diabetes,which highlights the potential role of platelet indices(PI)in predicting poor glucoregulation in patients wit...In this editorial,we discuss the recent article by Regassa et al,published in the World Journal of Diabetes,which highlights the potential role of platelet indices(PI)in predicting poor glucoregulation in patients with type 2 diabetes mellitus(T2DM).Given the high morbidity and mortality associated with T2DM,there is a constant need to find new and accessible methods for predicting and treating individuals with this condition.The pathophysiology of T2DM involves systemic inflammation,metabolic dysfunction,and an increased risk of vascular injury,which are commonly associated with the development of microvascular and macrovascular complications,such as cardiovascular diseases and neuropathies.The link between these complications and T2DM requires further elucidation but may be explained by prolonged exposure to high glycemic levels and increased advanced glycation end products.PI might play an important role in determining whether some individuals are prone to poor glucoregulation.Recent evidence encourages the scientific efforts to demonstrate the consistency of this role and its applicability in monitoring glucoregulation,underscoring the importance of the study by Regassa et al.展开更多
BACKGROUND While acute exposure to high-altitude hypoxic environments can lead to increased thrombosis risk,preventive measures are currently limited.Recently,human umbilical cord mesenchymal stem cell(hUC-MSC)transpl...BACKGROUND While acute exposure to high-altitude hypoxic environments can lead to increased thrombosis risk,preventive measures are currently limited.Recently,human umbilical cord mesenchymal stem cell(hUC-MSC)transplantation has been found effective in preventing and treating various clinical conditions,including thro-mbotic diseases.Platelets are crucial for thrombus formation,and theirα-granules are key determinants of platelet function.However,little is known about the influence of hUC-MSCs on plateletα-granules.METHODS Rats were assigned to three groups,namely,low-altitude,high-altitude,and hUC-MSC-treated groups.The low-altitude group was pretreated with normal saline and housed at an altitude of 1500 m.Rats in the high-altitude group received similar pretreatment and were housed in a simulated hypobaric hypoxia chamber with an altitude of 6500 m and oxygen partial pressure of 7.7 kPa.hUC-MSC-treated rats were pretreated with hUC-MSCs and exposed to hypoxic conditions.Aortic blood was collected after three days to assess platelet counts and mor-phology andα-granule release.RESULTS Compared to the low-altitude group,the high-altitude group exhibited significantly higher platelet counts,plasma levels of von Willebrand factor,platelet factor 4,beta-thromboglobulin,as well as surface P-selectin(CD62p)and p-protein kinase B,p-mitogen-activated protein kinase,and p-extracellular-signal regulated kinase expression in platelets.Platelet morphology in the high-altitude group was irregular,with extended pseudopodia and increasedα-granule densities.However,these changes were not apparent in the hUC-MSC-treated group.CONCLUSION Acute exposure to high-altitude hypoxia increased platelet counts,altered platelet morphology,and increasedα-granule density and release.These effects were mitigated by hUC-MSC treatment,mediated by the protein kinase B/mitogen-activated protein kinase/extracellular-signal regulated kinase pathway.The results indicate that hUC-MSCs may represent a promising and effective approach for the prevention and treatment of acute high-altitude-associated thrombosis,providing an experimental foundation for the development of clinical applications.展开更多
Objective This study aimed to evaluate the relationships of white blood cell(WBC)count,platelet(PLT)count,and PLT-to-WBC ratio(PWR)with muscle mass in Chinese older adults.Methods This cross-sectional analysis involve...Objective This study aimed to evaluate the relationships of white blood cell(WBC)count,platelet(PLT)count,and PLT-to-WBC ratio(PWR)with muscle mass in Chinese older adults.Methods This cross-sectional analysis involved 4,033 Chinese older adults aged≥65 years from the Healthy Ageing and Biomarkers Cohort Study.Muscle mass and total skeletal muscle mass index(TSMI)were measured by bioelectric impedance analysis.WBC,PLT,and PWR were measured using standard methods.Multivariate linear regression was used to examine the associations of WBC count,PLT count,and PWR with TSMI.Results High WBC count,PLT count,and PWR were associated with low TSMI,with coefficients of-0.0091(95%confidence interval[CI]:-0.0142 to-0.0041),-0.0119(95%CI:-0.0170 to-0.0068),and-0.0051(95%CI:-0.0102 to-0.0001).The associations between the three inflammatory indices and TSMI were linear.Stratified analyses indicated that the relationship between inflammatory markers and TSMI was more evident in male participants and in individuals aged<80 years than in their counterparts.Conclusion Elevated WBC count,PLT count,and PWR correlated with muscle mass loss.This study highlights the importance of regular monitoring of inflammatory markers as a potential strategy for the screening and management of sarcopenia in older adults.展开更多
Hypoxemia is a common pathological state characterized by low oxygen saturation in the blood.This condition compromises mucosal barrier integrity particularly in the gut and oral cavity.However,the mechanisms underlyi...Hypoxemia is a common pathological state characterized by low oxygen saturation in the blood.This condition compromises mucosal barrier integrity particularly in the gut and oral cavity.However,the mechanisms underlying this association remain unclear.This study used periodontitis as a model to investigate the role of platelet activation in oral mucosal immunopathology under hypoxic conditions.Hypoxia upregulated methyltransferase-like protein 4(METTL4)expression in platelets,resulting in N6-methyladenine modification of mitochondrial DNA(mtDNA).This modification impaired mitochondrial transcriptional factor A-dependent cytosolic mtDNA degradation,leading to cytosolic mtDNA accumulation.Excess cytosolic mt-DNA aberrantly activated the cGAS-STING pathway in platelets.This resulted in excessive platelet activation and neutrophil extracellular trap formation that ultimately exacerbated periodontitis.Targeting platelet METTL4 and its downstream pathways offers a potential strategy for managing oral mucosa immunopathology.Further research is needed to examine its broader implications for mucosal inflammation under hypoxic conditions.展开更多
BACKGROUND Liver cirrhosis and portal hypertension(PHT)can lead to lymphatic abnormalities and coagulation dysfunction.Because lymphangiogenesis may relieve liver cirrhosis and PHT,the present study investigated the g...BACKGROUND Liver cirrhosis and portal hypertension(PHT)can lead to lymphatic abnormalities and coagulation dysfunction.Because lymphangiogenesis may relieve liver cirrhosis and PHT,the present study investigated the gene expression alterations in the lymphatic system and the effectiveness of platelet-mediated lymphangiogenesis in improving liver cirrhosis and PHT.AIM To investigate the role of lymphangiogenesis in preclinical PHT models.METHODS Immunohistochemistry and transcriptome sequencing of bile duct ligation(BDL)and control lymphatic samples were conducted to reveal the indicated signaling pathways.Functional enrichment analyses were performed on the differentially expressed genes and hub genes.Adenoviral infection of vascular endothelial growth factor C(VEGF-C),plateletrich plasma(PRP),and VEGF3 receptor(VEGFR)inhibitor MAZ-51 was used as an intervention for the lymphatic system in PHT models.Histology,hemodynamic tests and western blot analyses were performed to demonstrate the effects of lymphatic intervention in PHT patients.RESULTS Lymphangiogenesis was increased in the BDL rat model.Transcriptome sequencing analysis of the extrahepatic lymphatic system revealed its close association with platelet adherence,aggregation,and activation.The role of PHT in the rat model was investigated by activating(PRP)and inhibiting(MAZ-51)the lymphatic system.PRP promoted lymphangiogenesis,which increased lymphatic drainage,alleviated portal pressure,reduced liver fibrosis,inhibited inflammation,inhibited angiogenesis,and suppressed mesenteric artery remodeling.MAZ-51 reversed the above improvements.CONCLUSION Via VEGF-C/VEGFR-3,platelets impede fibrosis,angiogenesis,and mesenteric artery remodeling,ultimately alleviating PHT.Thus,platelet intervention is a therapeutic approach for cirrhosis and PHT.展开更多
OBJECTIVE:To investigate the effects of gut microbes regulation of the trimethylamine(TMA)/flavin containing monooxygenase 3(FMO3)/trimethylamine N-oxide(TMAO)pathway on platelet aggregation in acute coronary syndrome...OBJECTIVE:To investigate the effects of gut microbes regulation of the trimethylamine(TMA)/flavin containing monooxygenase 3(FMO3)/trimethylamine N-oxide(TMAO)pathway on platelet aggregation in acute coronary syndrome(ACS)rats and the intervention of Huayu Qutan formula(化瘀祛痰方).METHODS:The ACS rats with syndrome of phlegm and blood stasis rats were established.Platelet,platelet aggregation,platelet activation markers and TMA/FMO3/TMAO pathway were detected.Metagenomics technology was employed to analyze the characteristics of the gut microbiota.RESULTS:Huayu Qutan formula and gut microbes could inhibit high platelet reactivity and regulate the TMA/FMO3/TMAO pathway.The dominant bacteria in ACS rats including but not limited to the major phyla,Firmicutes,Bacteroidetes,Actinobacteria,and Proteobacteria,also including some low abundance phyla,Fusobacteria,Verrucomicrobia,Spirochaetes,and Deferribacteres.The dominant bacteria in the Huayu Qutan formula group were Synergistetes,Deferribacteres,Deferribacteraceae,Faecalibacterium and Mucispirillum.In the Huayu Qutan formula combined with fecal bacteria enema group,the dominant bacteria were Verrucomicrobia,Verrucomicrobiae,Akkermansia and Verrucomicrobium.These gut microbiota were correlated with pathways such as Riboflavin metabolism and Arachidonic acid metabolism.CONCLUSION:Huayu Qutan formula may prevent ACS by modulating gut microbes Synergistetes,Faecalibacterium and Allobaculum,regulating the iron metabolism of Deferribacteres,and driving the TMA/FMO3/TMAO pathway to regulate gut microbiota function,and improving platelet aggregation.Akkermansia may serve as a promising probiotic,which could drive TMA/FMO3/TMAO pathway to regulate Arachidonic acid metabolism to improve platelet aggregation.The findings of this study provide a theoretical basis for the theory of"the heart is connected with the small intestine".展开更多
This letter comments on the recently published article in the World Journal of Gastroenterology,in which the authors demonstrated a strong link between lymphangiogenesis and the process of platelet adherence,aggregati...This letter comments on the recently published article in the World Journal of Gastroenterology,in which the authors demonstrated a strong link between lymphangiogenesis and the process of platelet adherence,aggregation,and activation by employing a rat model of liver cirrhosis caused by bile duct ligation(BDL).The authors applied both gain and loss of function approach by using platelet-rich plasma and vascular endothelial growth factor 3 receptor inhibitor MAZ-51 to activate and inhibit angiogenetic signaling in BDL rat model,respectively,to verify the crucial function of lymphangiogenesis in the development of liver cirrhosis and portal hypertension(PHT).In clinical practice,platelet transfusion has been applied to improve liver function in patients suffering from chronic liver disease and cirrhosis.Therefore,this study provides support for the application of platelet transfusion or pharmacological intervention of lymphangiogenesis as novel therapeutic approaches for liver cirrhosis and PHT.展开更多
Hyperlipidemia is a risk factor for clinically significant thrombotic events in cardiovascular diseases.Platelet reactivity in hyperlipidemic conditions is enhanced when platelet scavenger receptor CD36 recognizes oxi...Hyperlipidemia is a risk factor for clinically significant thrombotic events in cardiovascular diseases.Platelet reactivity in hyperlipidemic conditions is enhanced when platelet scavenger receptor CD36 recognizes oxidized lipids in oxidized low-density lipoprotein(ox-LDL)particles,a process that induces atherothrombosis.Sulforaphane(SFN)is a dietary isothiocyanate enriched in cruciferous vegetables and exerts multiple biological activities.The current study sought to investigate the efficacy of SFN on platelet hyperreactivity under hyperlipidemic conditions in vitro and in vivo.Using a series of platelet functional assays in human platelets in vitro,we demonstrated that SFN attenuated ox-LDL-increased platelet aggregation and activation(surface CD62P expression).Mechanistically,studies using pharmacological inhibitors clarified that these inhibitory effects of SFN were mainly modulated by down-regulating CD36-mediated activation of Src kinases,leading to enhanced activation of cyclic adenosine monophosphate/protein kinase A(cAMP/PKA)signaling,and resultant inhibition of NADPH oxidase 2(NOX2)-dependent generation of reactive oxygen species(ROS).Moreover,12-week supplementation of SFN-enriched broccoli sprout extract(BSE,0.06%diet)in hyperlipidemic C57BL/6J mice also decreased platelet hyperreactivity.Studies using pharmacological inhibitors of CD36,protein kinase A(PKA)and NOX2 showed that the efficacy of BSE supplementation was mainly through modulating CD36-mediated the cAMP/PKA/NOX2 signaling.Thus,through modulating the cAMP/PKA/NOX2 pathway and attenuating CD36-mediated platelet hyperreactivity,SFN may play important protective roles in atherothrombosis under hyperlipidemic conditions.展开更多
Objective:Xuebijing injection has been recommended as a therapeutic approach for individuals with severe and critical COVID-19.This study aims to explore the correlation of neutrophil to lymphocyte platelet ratio(NLPR...Objective:Xuebijing injection has been recommended as a therapeutic approach for individuals with severe and critical COVID-19.This study aims to explore the correlation of neutrophil to lymphocyte platelet ratio(NLPR)with the severity and prognosis of COVID-19,and the effect of XBJ on the prognosis of patients with COVID-19 in different inflammatory states.Methods:This was a retrospective study conducted at Wuhan Union Hospital in China.COVID-19patients admitted between November 1,2022 and February 1,2023 were included.In predicting prognosis for individuals with COVID-19,new inflammatory indicators were used,and their prognostic value was assessed by using Cox regression models and receiver operating characteristic curves.Furthermore,a calculation was made to determine the cutoff value for NLPR.Relative risk and Cox regression models were used to examine the effects of Xuebijing injection on prognosis in patient cohorts that had been stratified by the NLPR cutoff.Results:This research included 455 participants with COVID-19,with a mean age of 72 years.Several inflammatory indicators were found to be strongly correlated with prognosis,and NLPR shows the greatest predictive power.Patients with NLPR>3.29 exhibited a mortality rate of 17.3%,which was 6.2 times higher than in patients with NLPR≤3.29.Importantly,providing Xuebijing injection to patients with NLPR>3.29 was associated with a lower risk of 60-day all-cause mortality.However,there was no discernible improvement in survival among patients with NLPR≤3.29 who received Xuebijing injection.Conclusion:NLPR is the most reliable inflammatory marker for predicting prognosis among individuals with COVID-19,and can accurately identify individuals who may benefit from Xuebijing injection.展开更多
Platelet rich plasma(PRP)is an autologous blood product rich in platelets,showing promise in reducing inflammation and accelerating healing.While extensively utilized in plastic surgery,dermatology,and osteoarthritis ...Platelet rich plasma(PRP)is an autologous blood product rich in platelets,showing promise in reducing inflammation and accelerating healing.While extensively utilized in plastic surgery,dermatology,and osteoarthritis treatment,its application in anterior cruciate ligament(ACL)injuries is limited.This article examines PRP's potential in ACL reconstruction(ACLR),exploring its history,current usage,controversies and future directions.PRP has demonstrated significant early benefits in ligamentisation and vascularisation post-ACLR,though its long-term efficacy is inconsistent.Studies suggest that PRP may serve as both an adjunct therapy in ACLR to enhance initial healing and reduce postoperative complications,and as a non-surgical alternative for small ACL tears.Despite these promising findings,outcome variability necessitates further high-quality research to optimize PRP formulations and determine its most effective applications.The exploration of PRP as a treatment modality in ACLR offers promising but varied outcomes.PRP holds considerable promise as both an adjunct and alternative to traditional ACLR.This article underscores the need for targeted research to fully realize PRP's therapeutic potential in ACL treatment,aiming to inform future studies and clinical practices.By understanding PRP's mechanisms of efficacy and identifying the most beneficial patient populations,PRP could significantly impact orthopaedics and sports medicine,improving recovery pathways and patient outcomes.展开更多
BACKGROUND Lower limb atherosclerotic occlusive disease(LAOD)is a common complication in diabetic patients,leading to significant symptoms and reduced quality of life.AIM To investigate the efficacy of autologous plat...BACKGROUND Lower limb atherosclerotic occlusive disease(LAOD)is a common complication in diabetic patients,leading to significant symptoms and reduced quality of life.AIM To investigate the efficacy of autologous platelet-rich gel(APRG)as an innovative treatment for LAOD,focusing on clinical outcomes such as symptom relief,flow values,ankle-brachial index(ABI),walking distance,and claudication severity.METHODS This retrospective study involved an analysis of electronic medical records(EMR)from 150 patients diagnosed with LAOD.Participants were assigned to either a treatment group(n=80)or a control group(n=70).Both groups received standard care and underwent dressing changes.In addition,the treatment group was given APRG.Primary outcomes included changes in pain levels,wound healing rates,flow values assessed by plethysmography,ABI measurements,walking distance,and claudication severity.Statistical analyses were conducted to determine the significance of the results.RESULTS The APRG group showed significant improvements after 12 weeks,including a 70%reduction in pain,a 65%increase in wound healing rates,and an average walking distance increase of 150 meters.Flow values improved by 20%,with significant enhancements in ABI measurements(P<0.01).Additionally,patient satisfaction was higher,and 60%of patients reported improved claudication severity,confirming the efficacy of APRG in enhancing clinical outcomes for lower LAOD.CONCLUSION The APRG demonstrates significant efficacy in managing LAOD in diabetic patients,improving key clinical parameters including flow values,ABI,walking distance,and claudication.These findings support the need for further prospective studies to validate long-term efficacy and optimize treatment strategies.展开更多
AIM To assess the utility of NLR,PLR,IMT and contrast-enhanced ultrasound(CEUS)aspredictive markers for monitoring inflammatory responses and the disease activity in cardiac involvementin Takayasu’s arteritis.METHODS...AIM To assess the utility of NLR,PLR,IMT and contrast-enhanced ultrasound(CEUS)aspredictive markers for monitoring inflammatory responses and the disease activity in cardiac involvementin Takayasu’s arteritis.METHODS A cohort retrospective study encompassing 86 patients(43 withcardiac compromise and 43 without)was conducted.A comparative analysis of NLR,PLR,IMT,andCEUS between TA patients with and without cardiac compromise was undertaken.RESULTS The NLR and PLR of the heart damage group were significantly higher than those of the non heart damagegroup(2.9±1.0 vs.2.1±0.8,P<0.01;166±79 vs.117±51,P<0.01).The IMT and CEUS of the heartdamage group were significantly higher than those of the TA non heart damage group(2.6±0.6 vs.1.5±0.4,P<0.01;2.6±0.5 vs.1.6±0.6,P<0.01).The NLR level of the heart damage group was positivelycorrelated with CRP(r=0.42,P<0.01),and PLR was positively correlated with CRP and CEUS(r=0.34,P<0.05;r=0.35,P<0.05).The results of multiple logistic regression analysis showed that NLR,IMT,andCEUS were independent risk factors for TA and cardiac damage.The area under the ROC curve for NLRto determine cardiac damage is 0.865,with a cut-off value of 2.265,a sensitivity of 69.8%,and aspecificity of 90.7%.The area under the ROC curve for determining cardiac damage using PLR is 0.812,with a cut-off value of 111.275,a sensitivity of 76.7%,and a specificity of 79.1%.CONCLUSION NLR and PLR,in conjunction with contrast-enhanced ultrasound,can be employed to assessinflammatory response and the disease activity in cardiac involvement in Takayasu’s arteritis.展开更多
BACKGROUND Incisional hernias are a common complication of previous surgeries and remain a persistent issue in clinical practice,posing a significant burden on healthcare systems despite advances in education and tech...BACKGROUND Incisional hernias are a common complication of previous surgeries and remain a persistent issue in clinical practice,posing a significant burden on healthcare systems despite advances in education and technology.Surgical techniques,primarily involving the use of mesh to cover the abdominal wall gap,are widely used as a standard intervention strategy.AIM To examine the regeneration of the aponeurosis defect in the anterior abdominal wall in rats using regenerative mimetic factors of the extracellular matrix[ReGeneraTing Agent(RGTA)],adipose tissue micrografts(ATM),and platelet rich plasma(PRP)as regenerative agents.METHODS Regenerative agents such as RGTA,ATM,and PRP are gaining popularity.ATM involves autologous adipose tissue cells with mesenchymal stem cell markers and a high percentage of stromal vascular fraction cells.RGTAs are heparan sulfate(HS)mimetics that replace degraded HSs in damaged tissue,enhancing the quality and speed of repair.PRP is a concentrated plasma preparation containing seven fundamental proteins responsible for tissue production.An acellular dermal matrix is a biological implant free of cellular or antigenic components,making it an excellent material for reconstructive surgery.Polyglactin is a synthetic,absorbable mesh that loses 50%of its strength after fourteen days,providing initial support for new tissue regeneration before being completely absorbed.RESULTS Rats will undergo a laparotomy with a precise 2 cm by 2 cm excision of the anterior abdominal wall fascia below the umbilicus.They will be divided into sixteen groups,each receiving different combinations of regenerative factor injections into the denervated area in both non-contaminated and contaminated environments.A collagenelastin matrix will be used to join the aponeurosis edges,with an absorbable polyglactin mesh anchored over it.Samples will be taken for macroscopic,histological,and immunohistochemical evaluation of tissue regeneration.CONCLUSION Our study aims to demonstrate how these factors promote cell proliferation and healing of the denervated anterior abdominal wall,potentially reducing the frequency and complications of incisional hernias.This approach could offer a more economical and efficient treatment option compared to current costly methods.展开更多
Platelets are small anucleate cells generated from megakaryocytes in the bone marrow. Although platelet genera- tion, maturation, and clearance are still not fully understood, significant progress has been made in the...Platelets are small anucleate cells generated from megakaryocytes in the bone marrow. Although platelet genera- tion, maturation, and clearance are still not fully understood, significant progress has been made in the last 1-2 dec- ades. In blood circulation, platelets can quickly adhere and aggregate at sites of vascular injury, forming the platelet plug （i.e. the first wave of hemostasis）. Activated platelets can also provide negatively charged phosphatidylserine- rich membrane surface that enhances cell-based thrombin generation, which facilitates blood coagulation （i.e. the second wave of hemostasis）. Platelets therefore play central roles in hemostasis. However, the same process of hemostasis may also cause thrombosis and vessel occlusion, which are the most common mechanisms leading to heart attack and stroke following ruptured atherosclerotic lesions. In this review, we will introduce the classical mechanisms and newly discovered pathways of platelets in hemostasis and thrombosis, including fibrinogen-inde- pendent platelet aggregation and thrombosis, and the plasma fibronectin-mediated ＂protein wave＂ of hemostasis that precedes the classical first wave of hemostasis. Furthermore, we briefly discuss the roles of platelets in inflam- marion and atherosclerosis and the potential strategies to control atherothrombosis.展开更多
AIM:To investigate the role of human platelets in liver fibrosis.METHODS:Severe combined immunodeficiency(SCID)mice were administered CCl4and either phosphate-buffered saline(PBS group)or human platelet transfusions(h...AIM:To investigate the role of human platelets in liver fibrosis.METHODS:Severe combined immunodeficiency(SCID)mice were administered CCl4and either phosphate-buffered saline(PBS group)or human platelet transfusions(hPLT group).Concentrations of hepatocyte growth factor(HGF),matrix metallopeptidases(MMP)-9,and transforming growth factor-β(TGF-β)in the liver tissue were compared between the PBS and the hPLT groups by enzyme-linked immunosorbent assay(ELISA)and Western blotting.The effects of a human platelet transfusion on liver fibrosis included the fibrotic area,hydroxyproline content,and-smooth muscle actin(α-SMA)expression,which were evaluated by picrosirius red staining,ELISA,and immunohistochemical staining using an anti-mouse-SMA antibody,respectively.Phosphorylations of mesenchymal-epithelial transition factor(Met)and SMAD3,downstream signals of HGF and TGF-β,were compared between the two groups by Western blotting and were quantified using densitometry.Hepatocyte apoptosis was evaluated by terminal deoxynucleotidyl transferase dUTP nick end labeling.Furthermore,the accumulation of human platelets in the liver 2 h after platelet transfusion was compared between normal and fibrotic livers by immunohistochemical staining using an anti-human CD41 antibody.RESULTS:The fibrotic area and hydroxyproline content in the liver were both significantly lower in the hPLT group when compared to the PBS group(fibrotic area,1.7%±0.6%vs 2.5%±0.6%,P=0.03;hydroxyproline content,121±26 ng/g liver vs 156±47 ng/g liver,P=0.04).There was less α-smooth muscle actin staining in the hPLT group than in the PBS group(0.5%±0.1%vs 0.8%±0.3%,P=0.02).Hepatic expression levels of mouse HGF and MMP-9were significantly higher in the hPLT group than in the PBS group(HGF,109±13 ng/g liver vs 88±22 ng/g liver,P=0.03;MMP-9,113%±7%/GAPDH vs 92%±11%/GAPDH,P=0.04).In contrast,the concentration of mouse TGF-β in the liver tissue was significantly lower in the hPLT group than in the PBS group(22±5ng/g liver vs 39±6 ng/g liver,P=0.02).Phosphorylation of Met was more prevalent in the hPLT group than in the PBS group(37%±4%/GAPDH vs 20%±8%/GAPDH,P=0.03).Phosphorylation of SMAD3was weaker in the hPLT group than in the PBS group(60%±12%/GAPDH vs 84%±12%/GAPDH,P=0.1),although this difference was not significant.Furthermore,a lower rate of hepatocyte apoptosis was observed in the hPLT group than in the PBS group(5.9%±1.7%vs 2.9%±2.1%,P=0.02).Significant human platelet accumulation was observed in the fibrotic liver tissues,whereas few platelets accumulated in the normal liver.CONCLUSION:Human platelets inhibit liver fibrosis in SCID mice.Increased concentration of HGF in the liver suppresses hepatic stellate cell activation,induces MMPs,and inhibits hepatocyte apoptosis.展开更多
There is evidence that inflammatory bowel diseases (IBD) combine both inflammation and coagulation in their pathogenesis and clinical manifestations. Although platelets (PLT) are well known for their role in hemostasi...There is evidence that inflammatory bowel diseases (IBD) combine both inflammation and coagulation in their pathogenesis and clinical manifestations. Although platelets (PLT) are well known for their role in hemostasis, there are a rising number of studies supporting their considerable role as inflammatory amplifiers in chronic inflammatory conditions. IBD are associated with several alterations of PLT, including number, shape, and function, and these abnormalities are mainly attributed to the highly activated state of circulating PLT in IBD patients. When PLT activate, they increase in size, release a great variety of bio-active inflammatory and procoagulant molecules/particles, and express a variety of inflammatory receptors. These inflammatory products may represent a part of the missing link between coagulation and inflammation, and can be considered as possible IBD pathogenesis instigators. In clinical practice, thrombocytosis is associated both with disease activity and iron deficiency anemia. Controlling inflammation and iron replacement in anemic patients usually leads to a normalization of PLT count. The aim of this review is to update the role of PLT in IBD and present recent data revealing the possible therapeutic implications of anti-PLT agents in future IBD remedies.展开更多
文摘Platelet indices(PIs)including high mean platelet volume(MPV),plateletcrit(PLC),and platelet distribution width(PLDW)are associated with poor glycemic control.In addition,they can indicate prothrombotic and procoagulation risk among patients with diabetes.PI measurement is cheap,quick and fits healthcare system needs in remote outreaching areas in low-income countries.However,a broader insight into their clinical implications in diabetes is lacking.To achieve a wider understanding,we reviewed PubMed/MEDLINE,Google Scholar and Cochrane Library for relevant articles investigating the role of PIs in diabetes mellitus.No limitation to the publication date was applied,which included all articles published up to August 17,2024.The terms used were MPV,PLC,PLDW,platelet large cell ratio,glycated hemoglobin(HbA1c),PIs,platelet activity and diabetes mellitus.Out of the 790 articles retrieved,187 full texts were reviewed,and 44 were included.PIs,when measurements are done promptly and within 2 h,could be short-term pointers to glycemic control in the life span of the platelets(2 wk).PIs are easy to perform,cheap and useful in remote outreaching areas with limited facilities where measurement of HbA1c is not available or cost-effective.However,PIs are not specific and are affected by demographic factors,such as pregnancy,renal failure,medications,hemoglobin and duration of diabetes.PIs could be implemented with daily blood glucose to inform doctors in low-income countries about their patients'glycemic control and cardiovascular risk.An important application might be when blood glucose control is needed quickly(before elective surgery).
基金supported by the the National Key R&D Program of China(2024YFC2310000)the Key Project of Key Laboratory of VirologyBiosafety in the Wuhan Institute of Virology,Chinese Academy of Sciences(2024JZZD-02),the Youth Project of the Wuhan Institute of Virology,Chinese Academy of Sciences(2023QNTJ-03)+2 种基金the"Open Competition for Selecting the Best Candidates"Project of the Wuhan East Lake New Technology Development Zone(2022KJB117)the Natural Science Foundation of Hubei Province(2024AFB986)the Medical Science Research Project of Wuhan Health Commission(WX23B09).
文摘Crimean-Congo hemorrhagic fever(CCHF)is a hemorrhagic fever caused by infection with the CCHF virus(CCHFV)and has a mortality rate of up to 30%.Thrombocytopenia is a hallmark of CCHF;however,the mechanisms underlying this manifestation remain poorly understood.In addition to hemostasis,platelets play a crucial role in recognizing pathogens and mediating immune responses.We investigated the mechanisms underlying thrombocytopenia associated with CCHFV infection by analyzing the platelet transcriptome in mice.Interferon-induced transmembrane protein 3(IFITM3),a known antiviral factor,was significantly upregulated.The role of IFITM3 in response to CCHFV infection was characterized using the human megakaryoblast cell line MEG-01,considered a parental cell line of platelets.Although the CCHFV infection rate was limited,MEG-01 cells maintained the infection and replication of CCHFV,leading to increased IFITM3 protein expression.We demonstrated that IFITM3 overexpression efficiently inhibited CCHFV infection,whereas IFITM3 knockout promoted viral infection.An interaction between IFITM3 and the CCHFV glycoprotein Gc was identified,which suppressed CCHFV entry into cells.The IFITM3 CIL-TMD domain is critical for this interaction.These results suggest that IFITM3 is a restriction factor and plays an antiviral role during CCHFV infection.Elevated expression of IFITM3 in platelets indicates that this could be a common mechanism by which platelets protect against viruses,including CCHFV,which may reduce platelet consumption and destruction caused by CCHFV infection.These findings provide valuable insights into the pathogenesis of CCHF-associated thrombocytopenia and offer foundational theoretical support for future therapeutic strategies.
基金supported by the Key Program of the National Natural Science Foundation of China(81930090)the National Science Foundation for Distinguished Young Scholars of China(81725019)+2 种基金the National Natural Science Foundation of China(32171104,82273571,and 81874256)the Chongqing Natural Science Foundation(2023NSCQ-MSX0687,CSTB2023NSCQ-JQX0015,and cstc2015jcyjys10001)the Chongqing Talent Program(CQYC20220511002).
文摘Background:The essential roles of platelets in thrombosis have been well recognized.Unexpectedly,thrombosis is prevalent during thrombocytopenia induced by cytotoxicity of biological,physical and chemical origins,which could be suffered by military personnel and civilians during chemical,biological,radioactive,and nuclear events.Especially,thrombosis is considered a major cause of mortality from radiation injury-induced thrombocytopenia,while the underlying pathogenic mechanism remains elusive.Methods:A mouse model of radiation injury-induced thrombocytopenia was built by exposing mice to a sublethal dose of ionizing radiation(IR).The phenotypic and functional changes of platelets and megakaryocytes(MKs)were determined by a comprehensive set of in vitro and in vivo assays,including flow cytometry,flow chamber,histopathology,Western blotting,and chromatin immunoprecipitation,in combination with transcriptomic analysis.The molecular mechanism was investigated both in vitro and in vivo,and was consolidated using MK-specific knockout mice.The translational potential was evaluated using a human MK cell line and several pharmacological inhibitors.Results:In contrast to primitive MKs,mature MKs(mMKs)are intrinsically programmed to be apoptosis-resistant through reprogramming the Bcl-xL-BAX/BAK axis.Interestingly,mMKs undergo minority mitochondrial outer membrane permeabilization(MOMP)post IR,resulting in the activation of the cyclic GMP-AMP synthase-stimulator of IFN genes(cGAS-STING)pathway via the release of mitochondrial DNA.The subsequent interferon-β(IFN-β)response in mMKs upregulates a GTPase guanylate-binding protein 2(GBP2)to produce large and hyperreactive platelets that favor thrombosis.Further,we unmask that autophagy restrains minority MOMP in mMKs post IR.Conclusions:Our study identifies that megakaryocytic mitochondria-cGAS/STING-IFN-β-GBP2 axis serves as a fundamental checkpoint that instructs the size and function of platelets upon radiation injury and can be harnessed to treat platelet pathologies.
文摘This letter critically evaluates Jiang et al's article on the differentiation of benign and malignant liver lesions using Emax and platelet count.Despite notable findings,significant methodological and interpretative limitations are identified.The study lacks detailed assay conditions for Emax measurement,employs inadequate statistical methods without robust multivariate analysis,and does not provide clinically relevant threshold values.The nomogram's reliance on Emax as a major diagnostic contributor is questionable due to attenuation in hepatocellular carcinoma patients with cirrhosis.Moreover,the study's limitations,such as selection bias and confounding factors,are not adequately addressed.Future research should adopt more rigorous methodologies,including prospective studies with larger cohorts and standardized protocols for biomarker measurement,to enhance validity and clinical applicability.
文摘In this editorial,we discuss the recent article by Regassa et al,published in the World Journal of Diabetes,which highlights the potential role of platelet indices(PI)in predicting poor glucoregulation in patients with type 2 diabetes mellitus(T2DM).Given the high morbidity and mortality associated with T2DM,there is a constant need to find new and accessible methods for predicting and treating individuals with this condition.The pathophysiology of T2DM involves systemic inflammation,metabolic dysfunction,and an increased risk of vascular injury,which are commonly associated with the development of microvascular and macrovascular complications,such as cardiovascular diseases and neuropathies.The link between these complications and T2DM requires further elucidation but may be explained by prolonged exposure to high glycemic levels and increased advanced glycation end products.PI might play an important role in determining whether some individuals are prone to poor glucoregulation.Recent evidence encourages the scientific efforts to demonstrate the consistency of this role and its applicability in monitoring glucoregulation,underscoring the importance of the study by Regassa et al.
基金Supported by the Major Science and Technology Project of Gansu Province-Social Development Field,No.25ZDFA007Health Industry Research Funding Project of Gansu Province,No.GSWSKY2024-54+3 种基金Youth Science and Technology Fund Program of Gansu Province,No.21JR11RA014National Natural Science Foundation of China,No.81273568Health Industry Research Funding Project of Gansu Province,No.GSWSKY2022-03Logistics Scientific Research Independent Project of the PLA.
文摘BACKGROUND While acute exposure to high-altitude hypoxic environments can lead to increased thrombosis risk,preventive measures are currently limited.Recently,human umbilical cord mesenchymal stem cell(hUC-MSC)transplantation has been found effective in preventing and treating various clinical conditions,including thro-mbotic diseases.Platelets are crucial for thrombus formation,and theirα-granules are key determinants of platelet function.However,little is known about the influence of hUC-MSCs on plateletα-granules.METHODS Rats were assigned to three groups,namely,low-altitude,high-altitude,and hUC-MSC-treated groups.The low-altitude group was pretreated with normal saline and housed at an altitude of 1500 m.Rats in the high-altitude group received similar pretreatment and were housed in a simulated hypobaric hypoxia chamber with an altitude of 6500 m and oxygen partial pressure of 7.7 kPa.hUC-MSC-treated rats were pretreated with hUC-MSCs and exposed to hypoxic conditions.Aortic blood was collected after three days to assess platelet counts and mor-phology andα-granule release.RESULTS Compared to the low-altitude group,the high-altitude group exhibited significantly higher platelet counts,plasma levels of von Willebrand factor,platelet factor 4,beta-thromboglobulin,as well as surface P-selectin(CD62p)and p-protein kinase B,p-mitogen-activated protein kinase,and p-extracellular-signal regulated kinase expression in platelets.Platelet morphology in the high-altitude group was irregular,with extended pseudopodia and increasedα-granule densities.However,these changes were not apparent in the hUC-MSC-treated group.CONCLUSION Acute exposure to high-altitude hypoxia increased platelet counts,altered platelet morphology,and increasedα-granule density and release.These effects were mitigated by hUC-MSC treatment,mediated by the protein kinase B/mitogen-activated protein kinase/extracellular-signal regulated kinase pathway.The results indicate that hUC-MSCs may represent a promising and effective approach for the prevention and treatment of acute high-altitude-associated thrombosis,providing an experimental foundation for the development of clinical applications.
基金supported by the National Natural Science Foundation of China(grant nos.82025030,82222063,and 82388102)the National Key Research and Development Program of China(grant no.2023YFC3603400)。
文摘Objective This study aimed to evaluate the relationships of white blood cell(WBC)count,platelet(PLT)count,and PLT-to-WBC ratio(PWR)with muscle mass in Chinese older adults.Methods This cross-sectional analysis involved 4,033 Chinese older adults aged≥65 years from the Healthy Ageing and Biomarkers Cohort Study.Muscle mass and total skeletal muscle mass index(TSMI)were measured by bioelectric impedance analysis.WBC,PLT,and PWR were measured using standard methods.Multivariate linear regression was used to examine the associations of WBC count,PLT count,and PWR with TSMI.Results High WBC count,PLT count,and PWR were associated with low TSMI,with coefficients of-0.0091(95%confidence interval[CI]:-0.0142 to-0.0041),-0.0119(95%CI:-0.0170 to-0.0068),and-0.0051(95%CI:-0.0102 to-0.0001).The associations between the three inflammatory indices and TSMI were linear.Stratified analyses indicated that the relationship between inflammatory markers and TSMI was more evident in male participants and in individuals aged<80 years than in their counterparts.Conclusion Elevated WBC count,PLT count,and PWR correlated with muscle mass loss.This study highlights the importance of regular monitoring of inflammatory markers as a potential strategy for the screening and management of sarcopenia in older adults.
基金supported by the National Natural Science Foundation of China(82325012)the Youth Fund of the National Natural Science Foundation of China(82301043)+1 种基金the Natural Science Basic Research Program of Shaanxi (Program No.2024JC-YBQN-0980)the Shaanxi Key Scientific and Technological Innovation Team(2020TD-033).
文摘Hypoxemia is a common pathological state characterized by low oxygen saturation in the blood.This condition compromises mucosal barrier integrity particularly in the gut and oral cavity.However,the mechanisms underlying this association remain unclear.This study used periodontitis as a model to investigate the role of platelet activation in oral mucosal immunopathology under hypoxic conditions.Hypoxia upregulated methyltransferase-like protein 4(METTL4)expression in platelets,resulting in N6-methyladenine modification of mitochondrial DNA(mtDNA).This modification impaired mitochondrial transcriptional factor A-dependent cytosolic mtDNA degradation,leading to cytosolic mtDNA accumulation.Excess cytosolic mt-DNA aberrantly activated the cGAS-STING pathway in platelets.This resulted in excessive platelet activation and neutrophil extracellular trap formation that ultimately exacerbated periodontitis.Targeting platelet METTL4 and its downstream pathways offers a potential strategy for managing oral mucosa immunopathology.Further research is needed to examine its broader implications for mucosal inflammation under hypoxic conditions.
基金Supported by the National Natural Science Foundation of China,No.82100639,No.82200630,and No.81970526Postdoctoral Scientific Research Foundation of Shanghai Ninth People’s Hospital,Shanghai Jiao Tong University School of Medicine,No.202401023+3 种基金Clinical Research Program of Ninth People’s Hospital,Shanghai Jiao Tong University School of Medicine,No.JYLJ202124Shanghai Municipal Commission of Health and Family Planning,No.20244Y0195 and No.20234Y0132the Fundamental Research Program Funding of Ninth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine,No.JYZZ162Science Foundation of Xinjiang Uygur Natural Autonomous Region,No.2022D01F17.
文摘BACKGROUND Liver cirrhosis and portal hypertension(PHT)can lead to lymphatic abnormalities and coagulation dysfunction.Because lymphangiogenesis may relieve liver cirrhosis and PHT,the present study investigated the gene expression alterations in the lymphatic system and the effectiveness of platelet-mediated lymphangiogenesis in improving liver cirrhosis and PHT.AIM To investigate the role of lymphangiogenesis in preclinical PHT models.METHODS Immunohistochemistry and transcriptome sequencing of bile duct ligation(BDL)and control lymphatic samples were conducted to reveal the indicated signaling pathways.Functional enrichment analyses were performed on the differentially expressed genes and hub genes.Adenoviral infection of vascular endothelial growth factor C(VEGF-C),plateletrich plasma(PRP),and VEGF3 receptor(VEGFR)inhibitor MAZ-51 was used as an intervention for the lymphatic system in PHT models.Histology,hemodynamic tests and western blot analyses were performed to demonstrate the effects of lymphatic intervention in PHT patients.RESULTS Lymphangiogenesis was increased in the BDL rat model.Transcriptome sequencing analysis of the extrahepatic lymphatic system revealed its close association with platelet adherence,aggregation,and activation.The role of PHT in the rat model was investigated by activating(PRP)and inhibiting(MAZ-51)the lymphatic system.PRP promoted lymphangiogenesis,which increased lymphatic drainage,alleviated portal pressure,reduced liver fibrosis,inhibited inflammation,inhibited angiogenesis,and suppressed mesenteric artery remodeling.MAZ-51 reversed the above improvements.CONCLUSION Via VEGF-C/VEGFR-3,platelets impede fibrosis,angiogenesis,and mesenteric artery remodeling,ultimately alleviating PHT.Thus,platelet intervention is a therapeutic approach for cirrhosis and PHT.
基金Supported by National Natural Science Foundation of China Project:based on the Theory of“the Heart is in Harmony with the Small Intestine”to Explore the Influence and Mechanism of Gut Microbes on High Platelet Reactivity of Acute Coronary Syndrome with Phlegm and Blood Stasis Syndrome(No.82104841)Education Department of Liaoning Province Young Science and Technology Talents"Seedling"Project:to Explore the Effect and Mechanism of Huayu Qutan Formula on Platelet Function in Acute Coronary Syndrome Patients with Phlegm and Blood Stasis Syndrome after Percutaneous Coronary Intervention based on Intestinal Microbiome(No.L202039)。
文摘OBJECTIVE:To investigate the effects of gut microbes regulation of the trimethylamine(TMA)/flavin containing monooxygenase 3(FMO3)/trimethylamine N-oxide(TMAO)pathway on platelet aggregation in acute coronary syndrome(ACS)rats and the intervention of Huayu Qutan formula(化瘀祛痰方).METHODS:The ACS rats with syndrome of phlegm and blood stasis rats were established.Platelet,platelet aggregation,platelet activation markers and TMA/FMO3/TMAO pathway were detected.Metagenomics technology was employed to analyze the characteristics of the gut microbiota.RESULTS:Huayu Qutan formula and gut microbes could inhibit high platelet reactivity and regulate the TMA/FMO3/TMAO pathway.The dominant bacteria in ACS rats including but not limited to the major phyla,Firmicutes,Bacteroidetes,Actinobacteria,and Proteobacteria,also including some low abundance phyla,Fusobacteria,Verrucomicrobia,Spirochaetes,and Deferribacteres.The dominant bacteria in the Huayu Qutan formula group were Synergistetes,Deferribacteres,Deferribacteraceae,Faecalibacterium and Mucispirillum.In the Huayu Qutan formula combined with fecal bacteria enema group,the dominant bacteria were Verrucomicrobia,Verrucomicrobiae,Akkermansia and Verrucomicrobium.These gut microbiota were correlated with pathways such as Riboflavin metabolism and Arachidonic acid metabolism.CONCLUSION:Huayu Qutan formula may prevent ACS by modulating gut microbes Synergistetes,Faecalibacterium and Allobaculum,regulating the iron metabolism of Deferribacteres,and driving the TMA/FMO3/TMAO pathway to regulate gut microbiota function,and improving platelet aggregation.Akkermansia may serve as a promising probiotic,which could drive TMA/FMO3/TMAO pathway to regulate Arachidonic acid metabolism to improve platelet aggregation.The findings of this study provide a theoretical basis for the theory of"the heart is connected with the small intestine".
基金Supported by National Natural Science Foundation of China,No.82460461Medical Subject Leader of Yunnan Province(General Surgery),No.D-2024029+2 种基金Yunnan Fundamental Research Project for Excellent Young Scholars,No.202401AW070003The Young and Mid-aged Academic and Technical Leader Reserve Talent Program of Yunnan Province,No.202205AC160063Beijing Bethune Charitable Foundation,No.STLKY0089.
文摘This letter comments on the recently published article in the World Journal of Gastroenterology,in which the authors demonstrated a strong link between lymphangiogenesis and the process of platelet adherence,aggregation,and activation by employing a rat model of liver cirrhosis caused by bile duct ligation(BDL).The authors applied both gain and loss of function approach by using platelet-rich plasma and vascular endothelial growth factor 3 receptor inhibitor MAZ-51 to activate and inhibit angiogenetic signaling in BDL rat model,respectively,to verify the crucial function of lymphangiogenesis in the development of liver cirrhosis and portal hypertension(PHT).In clinical practice,platelet transfusion has been applied to improve liver function in patients suffering from chronic liver disease and cirrhosis.Therefore,this study provides support for the application of platelet transfusion or pharmacological intervention of lymphangiogenesis as novel therapeutic approaches for liver cirrhosis and PHT.
基金supported by the National Natural Science Foundation of China(82003451 and 82003455)Yunnan Fundamental Research Projects(202101AT070033)the Start-Up Fund for Introduction of High-level Talents to Dali University(YBS2021015).
文摘Hyperlipidemia is a risk factor for clinically significant thrombotic events in cardiovascular diseases.Platelet reactivity in hyperlipidemic conditions is enhanced when platelet scavenger receptor CD36 recognizes oxidized lipids in oxidized low-density lipoprotein(ox-LDL)particles,a process that induces atherothrombosis.Sulforaphane(SFN)is a dietary isothiocyanate enriched in cruciferous vegetables and exerts multiple biological activities.The current study sought to investigate the efficacy of SFN on platelet hyperreactivity under hyperlipidemic conditions in vitro and in vivo.Using a series of platelet functional assays in human platelets in vitro,we demonstrated that SFN attenuated ox-LDL-increased platelet aggregation and activation(surface CD62P expression).Mechanistically,studies using pharmacological inhibitors clarified that these inhibitory effects of SFN were mainly modulated by down-regulating CD36-mediated activation of Src kinases,leading to enhanced activation of cyclic adenosine monophosphate/protein kinase A(cAMP/PKA)signaling,and resultant inhibition of NADPH oxidase 2(NOX2)-dependent generation of reactive oxygen species(ROS).Moreover,12-week supplementation of SFN-enriched broccoli sprout extract(BSE,0.06%diet)in hyperlipidemic C57BL/6J mice also decreased platelet hyperreactivity.Studies using pharmacological inhibitors of CD36,protein kinase A(PKA)and NOX2 showed that the efficacy of BSE supplementation was mainly through modulating CD36-mediated the cAMP/PKA/NOX2 signaling.Thus,through modulating the cAMP/PKA/NOX2 pathway and attenuating CD36-mediated platelet hyperreactivity,SFN may play important protective roles in atherothrombosis under hyperlipidemic conditions.
基金supported by the National Natural Science Foundation of China(No.81571373,No.81601217 and No.82001491)Natural Science Foundation of Hubei Province of China(No.2017CFB627)+1 种基金Health Commission of Hubei Province Scientific Research Project(No.WJ2021M247)Scientific Research Fund of Wuhan Union Hospital(No.2019)。
文摘Objective:Xuebijing injection has been recommended as a therapeutic approach for individuals with severe and critical COVID-19.This study aims to explore the correlation of neutrophil to lymphocyte platelet ratio(NLPR)with the severity and prognosis of COVID-19,and the effect of XBJ on the prognosis of patients with COVID-19 in different inflammatory states.Methods:This was a retrospective study conducted at Wuhan Union Hospital in China.COVID-19patients admitted between November 1,2022 and February 1,2023 were included.In predicting prognosis for individuals with COVID-19,new inflammatory indicators were used,and their prognostic value was assessed by using Cox regression models and receiver operating characteristic curves.Furthermore,a calculation was made to determine the cutoff value for NLPR.Relative risk and Cox regression models were used to examine the effects of Xuebijing injection on prognosis in patient cohorts that had been stratified by the NLPR cutoff.Results:This research included 455 participants with COVID-19,with a mean age of 72 years.Several inflammatory indicators were found to be strongly correlated with prognosis,and NLPR shows the greatest predictive power.Patients with NLPR>3.29 exhibited a mortality rate of 17.3%,which was 6.2 times higher than in patients with NLPR≤3.29.Importantly,providing Xuebijing injection to patients with NLPR>3.29 was associated with a lower risk of 60-day all-cause mortality.However,there was no discernible improvement in survival among patients with NLPR≤3.29 who received Xuebijing injection.Conclusion:NLPR is the most reliable inflammatory marker for predicting prognosis among individuals with COVID-19,and can accurately identify individuals who may benefit from Xuebijing injection.
文摘Platelet rich plasma(PRP)is an autologous blood product rich in platelets,showing promise in reducing inflammation and accelerating healing.While extensively utilized in plastic surgery,dermatology,and osteoarthritis treatment,its application in anterior cruciate ligament(ACL)injuries is limited.This article examines PRP's potential in ACL reconstruction(ACLR),exploring its history,current usage,controversies and future directions.PRP has demonstrated significant early benefits in ligamentisation and vascularisation post-ACLR,though its long-term efficacy is inconsistent.Studies suggest that PRP may serve as both an adjunct therapy in ACLR to enhance initial healing and reduce postoperative complications,and as a non-surgical alternative for small ACL tears.Despite these promising findings,outcome variability necessitates further high-quality research to optimize PRP formulations and determine its most effective applications.The exploration of PRP as a treatment modality in ACLR offers promising but varied outcomes.PRP holds considerable promise as both an adjunct and alternative to traditional ACLR.This article underscores the need for targeted research to fully realize PRP's therapeutic potential in ACL treatment,aiming to inform future studies and clinical practices.By understanding PRP's mechanisms of efficacy and identifying the most beneficial patient populations,PRP could significantly impact orthopaedics and sports medicine,improving recovery pathways and patient outcomes.
文摘BACKGROUND Lower limb atherosclerotic occlusive disease(LAOD)is a common complication in diabetic patients,leading to significant symptoms and reduced quality of life.AIM To investigate the efficacy of autologous platelet-rich gel(APRG)as an innovative treatment for LAOD,focusing on clinical outcomes such as symptom relief,flow values,ankle-brachial index(ABI),walking distance,and claudication severity.METHODS This retrospective study involved an analysis of electronic medical records(EMR)from 150 patients diagnosed with LAOD.Participants were assigned to either a treatment group(n=80)or a control group(n=70).Both groups received standard care and underwent dressing changes.In addition,the treatment group was given APRG.Primary outcomes included changes in pain levels,wound healing rates,flow values assessed by plethysmography,ABI measurements,walking distance,and claudication severity.Statistical analyses were conducted to determine the significance of the results.RESULTS The APRG group showed significant improvements after 12 weeks,including a 70%reduction in pain,a 65%increase in wound healing rates,and an average walking distance increase of 150 meters.Flow values improved by 20%,with significant enhancements in ABI measurements(P<0.01).Additionally,patient satisfaction was higher,and 60%of patients reported improved claudication severity,confirming the efficacy of APRG in enhancing clinical outcomes for lower LAOD.CONCLUSION The APRG demonstrates significant efficacy in managing LAOD in diabetic patients,improving key clinical parameters including flow values,ABI,walking distance,and claudication.These findings support the need for further prospective studies to validate long-term efficacy and optimize treatment strategies.
文摘AIM To assess the utility of NLR,PLR,IMT and contrast-enhanced ultrasound(CEUS)aspredictive markers for monitoring inflammatory responses and the disease activity in cardiac involvementin Takayasu’s arteritis.METHODS A cohort retrospective study encompassing 86 patients(43 withcardiac compromise and 43 without)was conducted.A comparative analysis of NLR,PLR,IMT,andCEUS between TA patients with and without cardiac compromise was undertaken.RESULTS The NLR and PLR of the heart damage group were significantly higher than those of the non heart damagegroup(2.9±1.0 vs.2.1±0.8,P<0.01;166±79 vs.117±51,P<0.01).The IMT and CEUS of the heartdamage group were significantly higher than those of the TA non heart damage group(2.6±0.6 vs.1.5±0.4,P<0.01;2.6±0.5 vs.1.6±0.6,P<0.01).The NLR level of the heart damage group was positivelycorrelated with CRP(r=0.42,P<0.01),and PLR was positively correlated with CRP and CEUS(r=0.34,P<0.05;r=0.35,P<0.05).The results of multiple logistic regression analysis showed that NLR,IMT,andCEUS were independent risk factors for TA and cardiac damage.The area under the ROC curve for NLRto determine cardiac damage is 0.865,with a cut-off value of 2.265,a sensitivity of 69.8%,and aspecificity of 90.7%.The area under the ROC curve for determining cardiac damage using PLR is 0.812,with a cut-off value of 111.275,a sensitivity of 76.7%,and a specificity of 79.1%.CONCLUSION NLR and PLR,in conjunction with contrast-enhanced ultrasound,can be employed to assessinflammatory response and the disease activity in cardiac involvement in Takayasu’s arteritis.
文摘BACKGROUND Incisional hernias are a common complication of previous surgeries and remain a persistent issue in clinical practice,posing a significant burden on healthcare systems despite advances in education and technology.Surgical techniques,primarily involving the use of mesh to cover the abdominal wall gap,are widely used as a standard intervention strategy.AIM To examine the regeneration of the aponeurosis defect in the anterior abdominal wall in rats using regenerative mimetic factors of the extracellular matrix[ReGeneraTing Agent(RGTA)],adipose tissue micrografts(ATM),and platelet rich plasma(PRP)as regenerative agents.METHODS Regenerative agents such as RGTA,ATM,and PRP are gaining popularity.ATM involves autologous adipose tissue cells with mesenchymal stem cell markers and a high percentage of stromal vascular fraction cells.RGTAs are heparan sulfate(HS)mimetics that replace degraded HSs in damaged tissue,enhancing the quality and speed of repair.PRP is a concentrated plasma preparation containing seven fundamental proteins responsible for tissue production.An acellular dermal matrix is a biological implant free of cellular or antigenic components,making it an excellent material for reconstructive surgery.Polyglactin is a synthetic,absorbable mesh that loses 50%of its strength after fourteen days,providing initial support for new tissue regeneration before being completely absorbed.RESULTS Rats will undergo a laparotomy with a precise 2 cm by 2 cm excision of the anterior abdominal wall fascia below the umbilicus.They will be divided into sixteen groups,each receiving different combinations of regenerative factor injections into the denervated area in both non-contaminated and contaminated environments.A collagenelastin matrix will be used to join the aponeurosis edges,with an absorbable polyglactin mesh anchored over it.Samples will be taken for macroscopic,histological,and immunohistochemical evaluation of tissue regeneration.CONCLUSION Our study aims to demonstrate how these factors promote cell proliferation and healing of the denervated anterior abdominal wall,potentially reducing the frequency and complications of incisional hernias.This approach could offer a more economical and efficient treatment option compared to current costly methods.
基金supported in part by Canadian Institutes of Health Research(MOP 119540),National Natural Science Foundation of China-Canadian Institutes of Health Research(China-Canada Joint Health Research Initiative Program),Heart and Stroke Foundation of Canada(Ontario)supported by equipment Funds from St.Michael's Hospital,Canadian Blood Services,and Canada Foundation for Innovation
文摘Platelets are small anucleate cells generated from megakaryocytes in the bone marrow. Although platelet genera- tion, maturation, and clearance are still not fully understood, significant progress has been made in the last 1-2 dec- ades. In blood circulation, platelets can quickly adhere and aggregate at sites of vascular injury, forming the platelet plug （i.e. the first wave of hemostasis）. Activated platelets can also provide negatively charged phosphatidylserine- rich membrane surface that enhances cell-based thrombin generation, which facilitates blood coagulation （i.e. the second wave of hemostasis）. Platelets therefore play central roles in hemostasis. However, the same process of hemostasis may also cause thrombosis and vessel occlusion, which are the most common mechanisms leading to heart attack and stroke following ruptured atherosclerotic lesions. In this review, we will introduce the classical mechanisms and newly discovered pathways of platelets in hemostasis and thrombosis, including fibrinogen-inde- pendent platelet aggregation and thrombosis, and the plasma fibronectin-mediated ＂protein wave＂ of hemostasis that precedes the classical first wave of hemostasis. Furthermore, we briefly discuss the roles of platelets in inflam- marion and atherosclerosis and the potential strategies to control atherothrombosis.
基金Supported by Research grants from University of Tsukubathe Basic Research Support Program for Young Researcher
文摘AIM:To investigate the role of human platelets in liver fibrosis.METHODS:Severe combined immunodeficiency(SCID)mice were administered CCl4and either phosphate-buffered saline(PBS group)or human platelet transfusions(hPLT group).Concentrations of hepatocyte growth factor(HGF),matrix metallopeptidases(MMP)-9,and transforming growth factor-β(TGF-β)in the liver tissue were compared between the PBS and the hPLT groups by enzyme-linked immunosorbent assay(ELISA)and Western blotting.The effects of a human platelet transfusion on liver fibrosis included the fibrotic area,hydroxyproline content,and-smooth muscle actin(α-SMA)expression,which were evaluated by picrosirius red staining,ELISA,and immunohistochemical staining using an anti-mouse-SMA antibody,respectively.Phosphorylations of mesenchymal-epithelial transition factor(Met)and SMAD3,downstream signals of HGF and TGF-β,were compared between the two groups by Western blotting and were quantified using densitometry.Hepatocyte apoptosis was evaluated by terminal deoxynucleotidyl transferase dUTP nick end labeling.Furthermore,the accumulation of human platelets in the liver 2 h after platelet transfusion was compared between normal and fibrotic livers by immunohistochemical staining using an anti-human CD41 antibody.RESULTS:The fibrotic area and hydroxyproline content in the liver were both significantly lower in the hPLT group when compared to the PBS group(fibrotic area,1.7%±0.6%vs 2.5%±0.6%,P=0.03;hydroxyproline content,121±26 ng/g liver vs 156±47 ng/g liver,P=0.04).There was less α-smooth muscle actin staining in the hPLT group than in the PBS group(0.5%±0.1%vs 0.8%±0.3%,P=0.02).Hepatic expression levels of mouse HGF and MMP-9were significantly higher in the hPLT group than in the PBS group(HGF,109±13 ng/g liver vs 88±22 ng/g liver,P=0.03;MMP-9,113%±7%/GAPDH vs 92%±11%/GAPDH,P=0.04).In contrast,the concentration of mouse TGF-β in the liver tissue was significantly lower in the hPLT group than in the PBS group(22±5ng/g liver vs 39±6 ng/g liver,P=0.02).Phosphorylation of Met was more prevalent in the hPLT group than in the PBS group(37%±4%/GAPDH vs 20%±8%/GAPDH,P=0.03).Phosphorylation of SMAD3was weaker in the hPLT group than in the PBS group(60%±12%/GAPDH vs 84%±12%/GAPDH,P=0.1),although this difference was not significant.Furthermore,a lower rate of hepatocyte apoptosis was observed in the hPLT group than in the PBS group(5.9%±1.7%vs 2.9%±2.1%,P=0.02).Significant human platelet accumulation was observed in the fibrotic liver tissues,whereas few platelets accumulated in the normal liver.CONCLUSION:Human platelets inhibit liver fibrosis in SCID mice.Increased concentration of HGF in the liver suppresses hepatic stellate cell activation,induces MMPs,and inhibits hepatocyte apoptosis.
文摘There is evidence that inflammatory bowel diseases (IBD) combine both inflammation and coagulation in their pathogenesis and clinical manifestations. Although platelets (PLT) are well known for their role in hemostasis, there are a rising number of studies supporting their considerable role as inflammatory amplifiers in chronic inflammatory conditions. IBD are associated with several alterations of PLT, including number, shape, and function, and these abnormalities are mainly attributed to the highly activated state of circulating PLT in IBD patients. When PLT activate, they increase in size, release a great variety of bio-active inflammatory and procoagulant molecules/particles, and express a variety of inflammatory receptors. These inflammatory products may represent a part of the missing link between coagulation and inflammation, and can be considered as possible IBD pathogenesis instigators. In clinical practice, thrombocytosis is associated both with disease activity and iron deficiency anemia. Controlling inflammation and iron replacement in anemic patients usually leads to a normalization of PLT count. The aim of this review is to update the role of PLT in IBD and present recent data revealing the possible therapeutic implications of anti-PLT agents in future IBD remedies.
