Blood platelet and monocyte activations and relation to stages of liver cirrhosis

AIM: Blood platelets (pIt) and monocytes are the cells that play a crucial role in the pathogenesis of liver damage and liver cirrhosis (LC). In this paper, the analysis of mutual relationship between platelets and monocytes activation in LC was conducted. METHODS: Immunofluorescent flow cytometry was used to measure the percentage of activated platelet populations (CD62P, CD63), the percentage of plt-monocyte aggregates (pma) (CD41/CD45), and activated monocytes (CD11b, CD14, CD16) in the blood of 20 volunteers and 40 patients with LC. Platelet activation markers: sP-selectin, platelet factor 4 (PF4), beta-thromboglobulin (PTG) and monocyte chemotactic peptide-1 (MCP-1) were measured and compared in different stages of LC. RESULTS: Platelet activation with the increase in both βTG serum concentration and elevation of pIt population (CD62P and CD63 as well as MIF CD62P and CD63) is elevated as LC develops and thrombocytopenia rises. There is a positive correlation between medial intensity of fluorescence (MIF) CD62P and MIF CD63 in LC. We did not show any relationship between monocyte activation and pma level. SP-selectin concentration correlates positively with pIt count and pma, and negatively with stage of pIt activation and MIF CD62P and MIF CD63. There was no correlation between MCP-1 concentration and pIt, monocyte activation as well as pma level in LC. CD16 monocytes and MIF CD16 populations are significantly higher in the end stage of LC. A positive correlation occurs between the value of CDllb monocyte population and MIF CD14 and MIF CD16 on monocytes in LC. CONCLUSION: Platelet and monocyte activation plays an important role in LC. Platelet activation stage does not influence monocyte activation and production of pIt aggregates with monocytes in LC. With LC development, thrombocytopenia may be the result of pIt consumption in platelet-monocyte aggregates.

Red cell distribution width/platelet ratio estimates the 3-year risk of decompensation in Metabolic Dysfunction-Associated Steatotic Liver Disease-induced cirrhosis

BACKGROUND For compensated advanced chronic liver disease(cACLD)patients,the first decompensation represents a dramatically worsening prognostic event.Based on the first decompensation event(DE),the transition to decompensated advanced chronic liver disease(dACLD)can occur through two modalities referred to as acute decompensation(AD)and non-AD(NAD),respectively.Clinically Significant Portal Hypertension(CSPH)is considered the strongest predictor of decompensation in these patients.However,due to its invasiveness and costs,CSPH is almost never evaluated in clinical practice.Therefore,recognizing noninvasively predicting tools still have more appeal across healthcare systems.The red cell distribution width to platelet ratio(RPR)has been reported to be an indicator of hepatic fibrosis in Metabolic Dysfunction-Associated Steatotic Liver Disease(MASLD).However,its predictive role for the decompensation has never been explored.AIM In this observational study,we investigated the clinical usage of RPR in predicting DEs in MASLD-related cACLD patients.METHODS Fourty controls and 150 MASLD-cACLD patients were consecutively enrolled and followed up(FUP)semiannually for 3 years.At baseline,biochemical,clinical,and Liver Stiffness Measurement(LSM),Child-Pugh(CP),Model for End-Stage Liver Disease(MELD),aspartate aminotransferase/platelet count ratio index(APRI),Fibrosis-4(FIB-4),Albumin-Bilirubin(ALBI),ALBI-FIB-4,and RPR were collected.During FUP,DEs(timing and modaities)were recorded.CSPH was assessed at the baseline and on DE occurrence according to the available Clinical Practice Guidelines.RESULTS Of 150 MASLD-related cACLD patients,43(28.6%)progressed to dACLD at a median time of 28.9 months(29 NAD and 14 AD).Baseline RPR values were significantly higher in cACLD in comparison to controls,as well as MELD,CP,APRI,FIB-4,ALBI,ALBI-FIB-4,and LSM in dACLD-progressing compared to cACLD individuals[all P<0.0001,except for FIB-4(P:0.007)and ALBI(P:0.011)].Receiving operator curve analysis revealed RPR>0.472 and>0.894 as the best cut-offs in the prediction respectively of 3-year first DE,as well as its superiority compared to the other non-invasive tools examined.RPR(P:0.02)and the presence of baseline-CSPH(P:0.04)were significantly and independently associated with the DE.Patients presenting baseline-CSPH and RPR>0.472 showed higher risk of decompensation(P:0.0023).CONCLUSION Altogether these findings suggest the RPR as a valid and potentially applicable non-invasive tool in the prediction of timing and modalities of decompensation in MASLD-related cACLD patients.

Low preoperative platelet counts predict a high mortality after partial hepatectomy in patients with hepatocellular carcinoma

AIM： To assess the validity of our selection criteria for hepatectomy procedures based on indocyanine green disappearance rate （KICG）, and to unveil the factors affecting posthepatectomy mortality in patients with hepatocellular carcinoma （HCC）. METHODS： A retrospective analysis of 198 consecutive patients with HCC who underwent partial hepatectomies in the past 14 years was conducted. The selection criteria for hepatectomy procedures during the study period were KICG≥0.12 for hemihepatectomy, KICG≥0.10 for bisegmentectomy, KCG≥0.08 for monosegmentectomy, and KICG≥ 0.06 for nonanatomic hepatectomy. The hepatectomies were categorized into three types： major hepatectomy （hemihepatectomy or a more extensive procedure）, bisegmentectomy, and limited hepatectomy. Univariate （Fishers exact test） and multivariate （the logistic regression model） analyses were used. RESULTS： Postoperative mortality was 5% after major hepatectomy, 3% after bisegmentectomy, and 3% after limited hepatectomy. The bhree percentages were comparable （P = 0.876）. The platelet count of ≤ 10× 10^4/μL was the strongest independent factor for postoperative mortality on univariate （P = 0.001） and multivariate （risk ratio, 12.5; P= 0.029） analyses. No patient with a platelet count of 〉7.3× 10^4/μL died of postoperative morbidity, whereas 25% （6/24 patients） of patients with a platelet count of ≤7.3×10^4/μL died （P〈0.001）. CONCLUSION： The selection criteria for hepatectomy procedures based on KICG are generally considered valid, because of the acceptable morbidity and mortality with these criteria. The preoperative platelet count independently affects morbidity and mortality after hepatectomy, suggesting that a combination of KICG and platelet count would further reduce postoperative mortality.

Screening of active ingredients of Taohong Siwu Decoction on platelet membrane receptor

OBJECTIVE To screen the active ingredients preventing platelet aggregations from Taohong Siwu Decoction. METHODS Fresh blood from healthy adult volunteer was collected with vacuum tube for preparation of platelet suspension. Platelet suspension was incubated with Taohong Siwu Decoction for one hour at 37℃,then centrifuged. The precipitate was washed and desorbed with buffer solutions.The differences of chemical constituents between incubated and unincubated were identified with high performance liquid chromatography-diode array detector. RESULTS According to the chromatograph at 254 nm,at least three kinds of different components were detected in Taohong siwu decoction before and after incubated with platelet. CONCLUSION Platelet suspension can be used for screening active ingredients on platelet membrane receptor from the traditional Chinese medicine.

Clinical Observation on Shu Xin Yi Mai Capsules for Prevention of Recurrent Stricture after Coronary Artery Introducing Treatment

Shu Xin Yi Mai Capsules (舒心益脉胶囊) combined with western medicine was used in the routine treatment of 22 cases who successfully received coronary artery introducing therapy (Chinese-western medicine group),and the results was compared with the 26 cases treated routinely with simple western medicine in the control group (western medicine group).It was found that both the recurrence rate of angina pectoris and the incidence rate of recurrent stricture in the Chinese-western medicine group were significantly lower than that in the control group (both P<0.05).There was no significant difference between the two groups in expression of platelet activating molecules CD62P (a-granular membrane protein),CD63 (lysosome intact membrane protein) and CD41 (glucoprotein IIb) before the treatment,but with a significant difference after the treatment (P<0.05).

Real-Time Characterization of Fibrinogen Interaction with Modified Titanium Dioxide Film by Quartz Crystal Microbalance with Dissipation

The adsorption of fibrinogen can be used as a quick indicator of surface haemocompatibility because of its prominent role in coagulation and platelet adhesion. In this work the molecular interaction between fibrinogen and a modified titanium oxide surface/platelet has been studied by quartz crystal microbalanee with dissipation （QCM-D） in situ. In order to further characterize the conformation of adsorbed fibrinogen, αC and γ-chain antibody were used to check the orientation and denaturation of fibrinogen on solid surface. QCM-D investiga- tions revealed the fibrinogen have the trend to adsorb on hydropllilic surface in a side-on orientation by positively charged αC domains, which would reduce the exposure of platelet bonding site on γ chain and enable less platelet adhesion and be activated. These obser- vations suggest that certain conformations of adsorbed fibrinogen are less platelet adhesive than others, which opens a possibility for creating a non-platelet adhesive substrates.

BLOOD PLATELETS AND OXIDIZED LOW DENSITY LIPOPROTEIN

Functional morphological alterations of human blood platelets induced by oxidatively modified low density lipoprotein (LDL) were studied with an in vitro model by means of electron microscopy, reflection contrast microscopy and quantitative image analysis. The oxidized LDL (50-300 μg/ml) induced the disc-sphere transformation of platelets, the formation of pseudopodia, centralization of granules and degranulation. Platelet plasma membrane was damaged by oxidized LDL leading to a lower electron density of he cytoplasm compared to controls. In an incubation chamber, oxidized LDL-treated platelets sedimented onto the

Mortal condition in an unusual localization,analysis of isolated tongue and tongue base abscesses

BACKGROUND Tongue abscess(TA)is a very rare clinical condition and its treatment is very important.Surgical drainage is at the forefront in the treatment.Our study includes patients with tongue and tongue base abscesses.AIM To discuss the clinical and laboratory findings of these patients emphasizing the underlying causes and treatment options with the largest patient series in the English literature.METHODS We included patients with isolated TA who applied to our clinic between January 1,2020 and January 1,2023.Those who lack the recorded data,those who are not between the ages of 18-66,those who have not undergone surgery-interventional procedure,and those who have infection and/or abscess in another place were excluded from the study.RESULTS There were two female(18%)and nine male(82%)patients in our series consisting of 11 patients.Their ages ranged from 18 to 66,and the mean±SD was 48.63±16.3.Considering the localization of the abscess,three anterior abscesses(27%),two lateral abscesses(18%),and six abscesses at the base of the tongue(54%)were detected.CONCLUSION Tongue abscesses can cause acute upper airway obstruction and respiratory collapse.It may be necessary to act quickly for the tracheotomy procedure and this procedure can usually be performed under local anesthesia as intubation cannot be achieved.When we encounter an abscess in an unexpected organ,difficulties may be encountered in the management of the patient.

Effects of Dan Wei Powder (胆胃散) Tea Bag on Aggregation of Blood Platelet in vivo and in vitro

Objective: To observe effects of Dan Wei Powder (胆胃散 Powder for treating the gall bladder and stomach) Tea Bag (DWSTB) on the aggregation rate of blood platelet in vivo and in vitro. Methods: Increase of the platelet aggregation rate in the rat in vivo was induced by carrageenin, and increase of the rabbit platelet aggregation rate in vitro was induced by adenosine diphosphate (ADP) and collagen, respectively. The effects of DWSTB on the platelet aggregation rate were investigated in vivo and in vitro, respectively. Results: The maximum in vivo platelet aggregation rate in the rat was significantly decreased after administration of 2.0 and 4.0 g·kg-1 DWSTB (P<0.05.P<0.01). The maximum rabbit platelet aggregation rate induced by ADP and collagen in vitro were suppressed significantly by 2.0-16.0 mg·mL-1 and 2.0-8.0 mg·mL-1 DWSTB, respectively (P<0.05.P<0.01). And the effect of DWSTB on platelet aggregation was raised with increase ofits dose. Conclusion: Dan Wei Powder Tea Bag can restrain the aggregation of platelet in vivo and in vitro.

Correlation study between pre-operative platelet aggregation rate and peri-operative blood product application in patients with off-pump coronary artery bypass grafting

Objective To explore the impact of pre-operative platelet aggregation rate(PAR)on off-pump coronary artery bypass grafting(OPCABG),meanwhile to study the relationship between platelet function and blood product application during peri-operative period in relevant patients.Methods A total of 172 patients receiving OPCABG in our hospita from 2014-01 to 2015-09 were en-

Platelet Distribution Width on Admission Predicts In-Stent Restenosis in Patients with Coronary Artery Disease and Type 2 Diabetes Mellitus Treated with Percutaneous Coronary Intervention

Background： It is known that there is a definite association between platelet distribution width （PDW） and poor prognosis in patients with coronary artery disease （CAD） and type 2 diabetes mellitus （T2DM）. However, there are no data available regarding the prognostic significance of PDW for in-stent restenosis （ISR） in patients with CAD and T2DM. We aimed to determine the value of PDW on admission that predicted ISR in patients with CAD and T2DM. Methods： Between January 2012 and December 2013, a total of 5232 consecutive patients diagnosed with CAD and T2DM undergoing percutaneous coronary intervention were admitted. Three years of retrospective tbllow-up was undertaken. A total of 438 patients with second angiography operations were included. ISR was defined as ≥50% luminal stenosis of the stent or peri-stent segments. Continuous data were presented as the mean ± standard deviation or median （P25, P75） and were compared by one-way analysis of variance or Kruskal-Wallis H-test. Categorical variables were presented as percentages and were compared by Chi-square test or Fisher＇s exact test. The association between PDW and ISR was calculated by logistic regression analysis. A two-sided value of P 〈 0.05 was considered statistically significant. Statistical analyses were pertbrmed by SPSS version 22.0 for windows. Results： Fifty-nine patients with ISR, accounting for 13.5% of the total, were included. ISR was significantly more frequent in patients with higher PDW quartiles compared with lower quartiles. We observed that PDW had a strong relationship with mean platelet volume （r=0.6474 95% confidence interval [CI]： 0.535-0.750, P 〈 0.0001 ）. The receiver-operating characteristic curves showed that the PDW cutoffvalue for predicting ISR rate was 13.65 fl with sensitivity of 59.3% and specificity of 72.4% （area under curve [AUC] = 0.701,95% CI： 0.625-0.777, P 〈 0.001 ）. Multivariate analysis showed that the risk of ISR increased approximately 30% when PDW increased one unit （odds ratio [OR]： 1.289, 95% （7： I. 110 1.498, P = 0.001 ）. Patients with higher PDW, defined as more than 13.65 fl, had a 4-fold higher risk oflSR compared with lower PDW （OR： 4.241,95% CI： 1.879 9.572, P = 0.001 ）. Furthemlore, when patients were divided by PDW quartiles values, PDW was able to predict ISR （Q2： OR = 0.762, 95% CI： 0.189-3.062, P= 0.762; Q3： OR = 2.782, 95% CI：0.865 8.954, P = 0.086; and Q4： OR = 3.849, 95% CI： 1.225 12.097, P - 0.021, respectively; P for trend 〈0.0001 ）. Conclusion： PDW is an independent predictor of ISR in patients with CAD and T2DM.

Head to Head Comparison of Two Point-of-care Platelet Function Tests Used for Assessment of On-clopidogrel Platelet Reactivity in Chinese Acute Myocardial Infarction Patients Undergoing Percutaneous Coronary Intervention

Background：Platelet function tests are widely used in clinical practice to guide personalized antiplatelet therapy.In China,the thromboelastography （TEG） test has been well accepted in clinics,whereas VerifyNow,mainly used for scientific research,has not been used in routine clinical practice.The aim of the current study was to compare these two point-of-care platelet function tests and to analyze the consistency between the two tests for evaluating on-clopidogrel platelet reactivity in Chinese acute myocardial infarction patients undergoing percutaneous coronary intervention （PCI）.Methods：A total of 184 patients admitted to Fuwai Hospital between August 2014 and May 2015 were enrolled in the study.On-clopidogrel platelet reactivity was assessed 3 days after PCI by TEG and VerifyNow using adenosine diphosphate as an agonist.Based on the previous reports,an inhibition of platelet aggregation （IPA） 〈30% for TEG or a P2Y12 reaction unit （PRU） 〉230 for VerifyNow was defined as high on-clopidogrel platelet reactivity （HPR）.An IPA 〉70% or a PRU 〈178 was defined as low on-clopidogrel platelet reactivity （LPR）.Correlation and agreement between the two methods were analyzed using the Spearman correlation coefficient （r） and kappa value （κ）,respectively.Results：Our results showed that VerifyNow and TEG had a moderate but significant correlation in evaluating platelet reactivity （r =-0.511）.A significant although poor agreement （κ =0.225） in identifying HPR and a significantly moderate agreement in identifying LPR （κ =0.412） were observed between TEG and VerifyNow.By using TEG as the reference for comparison,the cutoffvalues of VerifyNow for the Chinese patients in this study were identified as PRU 〉205 for HPR and PRU 〈169 for LPR.Conclusions：By comparing VerifyNow to TEG which has been widely used in clinics,VerifyNow could be an attractive alternative to TEG for monitoring on-clopidogrel platelet reactivity in Chinese patients.

Protectin DX Exhibits Protective Effects in Mouse Model of Lipopolysaccharide-Induced Acute Lung Injury

Background：Acute lung injury （ALI） is a severe disease with high mortality and poor prognosis.Protectin DX （PDX）,a pro-resolving lipid mediator,exhibits protective effects in ALI.Our experiment aimed to explore the effects and related mechanisms of PDX in mice with ALI induced by lipopolysaccharide （LPS）.Methods：BALB/c mice were randomly divided into five groups：sham,LPS,LPS plus 1 ng ofPDX （LPS ＋ PDX-1 ng）,LPS plus 10 ng ofPDX （LPS ＋ PDX-10 ng）,and LPS plus 100 ng ofPDX （LPS ＋ PDX-100 ng）.Bronchoalveolar lavage fluids （BALFs） were collected after 24 h,and total cells,polymorphonuclear leukocytes,monocyte-macrophages,and lymphocytes in BALF were enumerated.The concentration of interleukin （IL）-1 β3,IL-6,IL-10,tumor necrosis factor-alpha （TNF-α）,macrophage inflammatory protein （MIP）-1 cα,and MIP-2 in BALF was determined,and histopathological changes of the lung were observed.The concentration of protein in BALF and lung wet/dry weight ratios were detected to evaluate pulmonary edema.After determining the optimal dose of PDX,neutrophil-platelet interactions in whole blood were evaluated by flow cytometry.Results：The highest dose of PDX （100 ng/mouse） failed to provide pulmonary protective effects,whereas lower doses of PDX （1 ng/mouse and 10 ng/mouse）,especially 1 ng PDX,alleviated pulmonary histopathological changes,mitigated LPS-induced ALI and pulmonary edema,inhibited neutrophil infiltration,and reduced pro-inflammatory mediator （IL-1β,IL-6,TNF-α,and MIP-lα） levels.Meanwhile,1 ng PDX exhibited pro-resolving functions in ALI including upregulation of monocyte-macrophage numbers and anti-inflammatory mediator IL-l 0 levels.The flow cytometry results showed that PDX could inhibit neutrophil-platelet interactions in ALI.Conclusion：PDX exerts protective effects in LPS-inducedALI by mitigating pulmonary inflammation and abrogating neutrophil-platelet interactions.

Anti-embolic effect of Taorenchengqi Tang in rats with embolic stroke induced by occluding middle cerebral artery

OBJECTIVE: To investigate the anti-embolic effect of Taorenchengqi Tang(TRCQT), a formulas from Traditional Chinese Medicine, plus aspirin in rats with embolic stroke induced by selective occlusion of the middle cerebral artery(MCA). Possible side effects of hemorrhagic incident and other bleeding events and anti-platelet effect were also explored.METHODS: Ninety rats were randomly separatedinto 9 groups(n = 10): group 1 a sham-operated group(n = 10); groups 2 and 3 orally treated with an isovolumetric solvent(distilled water) for 1 and3 months, followed by thromboembolic occlusion(n = 10); groups 4 and 5 orally treated with aspirin(5 mg/kg) alone for 1 and 3 months, followed by thromboembolic occlusion(n = 10); groups 6 and 7orally treated with TRCQT(0.5 g/kg) alone for 1 and3 months, followed by thromboembolic occlusion(n = 10); groups 8 and 9 orally treated with TRCQT plus aspirin for 1 and 3 months, respectively followed by thromboembolic occlusion(n = 10). The ischemic stroke in rats was induced by selective MCA occlusion. One was orally administered. After the treatments, rats' brains were removed, sectioned and stained with triphenyltetrazolium chloride(TTC) for infarct volume measurement. The incidence of subarachnoid hemorrhage(SAH) and intracerebral hemorrhage(ICH) were observed. A potential gastric bleeding side effect was assessed by measuring hemoglobin(Hb), and prothrombin time(PT). Collagen-induced platelet activation and tail vein bleeding time were measured.RESULTS: Treatment with TRCQT alone or in combination with aspirin reduced infarct volume for 1(P < 0.05), and 3(P < 0.01) months without SAH and ICH incidences, and gastric bleeding. TRCQT treatment for 1 month was also not altered PT. Moreover, a concentration dependent inhibition of collagen-induced platelet activation, followed by increasing of tail vein bleeding time was observed after TRCQT treatment.CONCLUSION: Either TRCQT alone or TRCQT plus aspirin exhibits potent neuroprotective effect by reducing infarct volume without changing the status of SAH, ICH and gastric bleeding possibly via inhib-iting the platelet activation and increasing bleeding time.

Hypercoagulability in cancer patients grouped by syndromes differentiated with the theory of abnormal hilit in traditional Uyghur medicine

OBJECTIVE:To investigate the relationship in malignant-neoplasm patients of hypercoagulability between syndromes differentiated with the theory of abnormal hilit in traditional Uyghur medicine(TUM).METHODS:A total of 248 patients with malignant tumors were enrolled.Based on the theory of TUM they were divided into two groups:abnormal Savda and abnormal Non-Savda(including abnormal Khan,abnormal Sepra and abnormal Belghem types);fifty healthy volunteers were selected as controls.Platelet(PLT),prothrombin time(PT),plasma fibrinogen(FIB),thrombin time(TT),activated partial thromboplastin time(aPTT)and D-Dimer(D-D)were measured in both groups.RESULTS:Compared with the control and abnor-mal Non-Savda groups,in the abnormal Savda group the PLT count increased(P<0.05),the PT was lengthened(P<0.01),and the FIB significantly increased(P<0.01).D-Ds in the three groups were significantly different(P<0.05).No significant difference was found inTT and aPTT values(P>0.05).CONCLUSION:Hypercoagulability existed in patients with malignant tumors in the different types of TUM syndromes,especially in the abnormal Savda group;this was characterized by increased blood viscosity,platelet aggregation and thrombosis.D-D appears to be a significant predictor for the therapeutic effect of TUM in relation to malignant tumor therapies.