Hypidone hydrochloride(YL-0919)ameliorates functional deficits after traumatic brain injury in mice by activating the sigma-1 receptor for antioxidation

Traumatic brain injury involves complex pathophysiological mechanisms,among which oxidative stress significantly contributes to the occurrence of secondary injury.In this study,we evaluated hypidone hydrochloride(YL-0919),a self-developed antidepressant with selective sigma-1 receptor agonist properties,and its associated mechanisms and targets in traumatic brain injury.Behavioral experiments to assess functional deficits were followed by assessment of neuronal damage through histological analyses and examination of blood-brain barrier permeability and brain edema.Next,we investigated the antioxidative effects of YL-0919 by assessing the levels of traditional markers of oxidative stress in vivo in mice and in vitro in HT22 cells.Finally,the targeted action of YL-0919 was verified by employing a sigma-1 receptor antagonist(BD-1047).Our findings demonstrated that YL-0919 markedly improved deficits in motor function and spatial cognition on day 3 post traumatic brain injury,while also decreasing neuronal mortality and reversing blood-brain barrier disruption and brain edema.Furthermore,YL-0919 effectively combated oxidative stress both in vivo and in vitro.The protective effects of YL-0919 were partially inhibited by BD-1047.These results indicated that YL-0919 relieved impairments in motor and spatial cognition by restraining oxidative stress,a neuroprotective effect that was partially reversed by the sigma-1 receptor antagonist BD-1047.YL-0919 may have potential as a new treatment for traumatic brain injury.

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.

Emerging insights into the function of very long chain fatty acids at cerebellar synapses

Very long chain-saturated and-polyunsaturated fatty acids(VLC-SFA and VLC-PUFA, respectively) are a functionally important class of fatty acids containing 28 carbons or more in their acyl chain. They are synthesized by the elongation of very long fatty acids-4(ELOVL4) enzyme, expressed mainly in the brain, retina, skin, testes, and meibomian gland, where these fatty acids are found(Agbaga et al., 2008). Further, these organs exhibit tissuespecific VLC-PUFA and VLC-SFA biosynthesis and incorporation into complex lipids for specific functions. In the brain, skin, and Meibomian glands, the ELOVL4 mainly makes VLC-SFA, which are incorporated into complex sphingolipids. In the retina, the ELOVL4 makes VLC-PUFA that are incorporated into phosphatidylcholine, that are critical for visual function, while in testes and sperm, the VLC-PUFA are incorporated into sphingolipids that are critical for fertility(Yeboah et al., 2021).

The complex role of protocadherin-19 in brain function:a focus on the oxytocin system

Mutations in the protocadherin-19(PCDH19)gene(Xq22.1)cause the X-linked syndrome known as developmental and epileptic encephalopathy 9(DEE9,OMIM#300088)(Dibbens et al.,2008).DEE9 is characterized by early-onset clustering epilepsy associated with intellectual disability ranging from mild to profound,autism spectrum disorder,and other neuropsychiatric features including schizophrenia,anxiety,attentiondeficit/hyperactivity,and obsessive or aggressive behaviors.While seizures may become less frequent in adolescence,psychiatric comorbidities persist and often worsen with age(Dibbens et al.,2008;Kolc et al.,2020).

Neuropeptide cholecystokinin:a key neuromodulator for hippocampal functions

Spatial memory is crucial for survival within external surroundings and wild environments.The hippocampus,a critical hub for spatial learning and memory formation,has received extensive investigations on how neuromodulators shape its functions(Teixeira et al.,2018;Zhang et al.,2024).However,the landscape of neuromodulations in the hippocampal system remains poorly understood because most studies focus on classical monoamine neuromodulators,such as acetylcholine,serotonin,dopamine,and noradrenaline.The neuropeptides,comprising the most abundant neuromodulators in the central nervous system,play a pivotal role in neural information processing in the hippocampal system.Cholecystokinin(CCK),one of the most abundant neuropeptides,has been implicated in regulating various physiological and neurobiological statuses(Chen et al.,2019).CCK-A receptor(CCK-AR)and CCK-B receptors(CCK-BR)are two key receptors mediating the biological functions of CCK,both of which belong to class-A sevenfold transmembrane G protein-coupled receptors(Nishimura et al.,2015).CCK-AR preferentially reacts to sulfated CCK,whereas CCK-BR binds both CCK and gastrin with similar affinities(Ding et al.,2022).The expression patterns of CCK-AR and CCK-BR are distinct,implying that CCK has various functions in target regions.For instance,CCK-AR is widely expressed in the GI and brain subregions and is hence implicated in the control of digestive function and satiety regulation.Conversely,CCK-BR is abundantly and widely distributed in the central nervous system,which majorly regulates anxiety,learning,and memory(Ding et al.,2022).However,the roles of endogenous CCK and CCK receptors in regulating hippocampal function at electrophysiological and behavioral levels have received less attention.

Corrigendum: MicroRNA-502-3p regulates GABAergic synapse function in hippocampal neurons

There is an error in the name of the cell line in the abstract of the published paper“MicroRNA-502-3p regulates GABAergic synapse function in hippocampal neurons”published on pages 2698-2707,Issue 12,Volume 19 of Neural Regeneration Research(Sharma et al.,2024),because of oversight during final proof checking.The correct description should be“human-GABA receptor A-α1/β2/γ2L human embryonic kidney(HEK)recombinant cell line.”The authors apologize for any inconvenience this correction may cause for readers and editors of Neural Regeneration Research.

Chondroitinase ABC combined with Schwann cell transplantation enhances restoration of neural connection and functional recovery following acute and chronic spinal cord injury

Schwann cell transplantation is considered one of the most promising cell-based therapy to repair injured spinal cord due to its unique growth-promoting and myelin-forming properties.A the Food and Drug Administration-approved Phase I clinical trial has been conducted to evaluate the safety of transplanted human autologous Schwann cells to treat patients with spinal cord injury.A major challenge for Schwann cell transplantation is that grafted Schwann cells are confined within the lesion cavity,and they do not migrate into the host environment due to the inhibitory barrier formed by injury-induced glial scar,thus limiting axonal reentry into the host spinal cord.Here we introduce a combinatorial strategy by suppressing the inhibitory extracellular environment with injection of lentivirus-mediated transfection of chondroitinase ABC gene at the rostral and caudal borders of the lesion site and simultaneously leveraging the repair capacity of transplanted Schwann cells in adult rats following a mid-thoracic contusive spinal cord injury.We report that when the glial scar was degraded by chondroitinase ABC at the rostral and caudal lesion borders,Schwann cells migrated for considerable distances in both rostral and caudal directions.Such Schwann cell migration led to enhanced axonal regrowth,including the serotonergic and dopaminergic axons originating from supraspinal regions,and promoted recovery of locomotor and urinary bladder functions.Importantly,the Schwann cell survival and axonal regrowth persisted up to 6 months after the injury,even when treatment was delayed for 3 months to mimic chronic spinal cord injury.These findings collectively show promising evidence for a combinatorial strategy with chondroitinase ABC and Schwann cells in promoting remodeling and recovery of function following spinal cord injury.

Emerging role of A-kinase anchoring protein 5 signaling in reward circuit function

There is a strong evidence supporting the hypothesis of synaptic dysfunction as a major contributor to neural circuit and network disruption underlying emotional and mood dysregulation in psychiatric disorders(Simmons et al.,2024).Diverse sets of distinct molecular signaling pathways converge on the synapse to regulate synaptogenesis,synaptic function,and synaptic plasticity in brain regions and circuits through complex interactions organized by numerous multivalent protein scaffolds,including the family of proteins known as A-kinase anchoring proteins(AKAPs).

Resting-state brain network remodeling after different nerve reconstruction surgeries:a functional magnetic resonance imaging study in brachial plexus injury rats

Distinct brain remodeling has been found after different nerve reconstruction strategies,including motor representation of the affected limb.However,differences among reconstruction strategies at the brain network level have not been elucidated.This study aimed to explore intranetwork changes related to altered peripheral neural pathways after different nerve reconstruction surgeries,including nerve repair,endto-end nerve transfer,and end-to-side nerve transfer.Sprague–Dawley rats underwent complete left brachial plexus transection and were divided into four equal groups of eight:no nerve repair,grafted nerve repair,phrenic nerve end-to-end transfer,and end-to-side transfer with a graft sutured to the anterior upper trunk.Resting-state brain functional magnetic resonance imaging was obtained 7 months after surgery.The independent component analysis algorithm was utilized to identify group-level network components of interest and extract resting-state functional connectivity values of each voxel within the component.Alterations in intra-network resting-state functional connectivity were compared among the groups.Target muscle reinnervation was assessed by behavioral observation(elbow flexion)and electromyography.The results showed that alterations in the sensorimotor and interoception networks were mostly related to changes in the peripheral neural pathway.Nerve repair was related to enhanced connectivity within the sensorimotor network,while end-to-side nerve transfer might be more beneficial for restoring control over the affected limb by the original motor representation.The thalamic-cortical pathway was enhanced within the interoception network after nerve repair and end-to-end nerve transfer.Brain areas related to cognition and emotion were enhanced after end-to-side nerve transfer.Our study revealed important brain networks related to different nerve reconstructions.These networks may be potential targets for enhancing motor recovery.

Enhancement of motor functional recovery in thoracic spinal cord injury: voluntary wheel running versus forced treadmill exercise

Spinal cord injury necessitates effective rehabilitation strategies, with exercise therapies showing promise in promoting recovery. This study investigated the impact of rehabilitation exercise on functional recovery and morphological changes following thoracic contusive spinal cord injury. After a 7-day recovery period after spinal cord injury, mice were assigned to either a trained group(10 weeks of voluntary running wheel or forced treadmill exercise) or an untrained group. Bi-weekly assessments revealed that the exercise-trained group, particularly the voluntary wheel exercise subgroup, displayed significantly improved locomotor recovery, more plasticity of dopaminergic and serotonin modulation compared with the untrained group. Additionally, exercise interventions led to gait pattern restoration and enhanced transcranial magnetic motor-evoked potentials. Despite consistent injury areas across groups, exercise training promoted terminal innervation of descending axons. In summary, voluntary wheel exercise shows promise for enhancing outcomes after thoracic contusive spinal cord injury, emphasizing the role of exercise modality in promoting recovery and morphological changes in spinal cord injuries. Our findings will influence future strategies for rehabilitation exercises, restoring functional movement after spinal cord injury.

Pharmacological targeting cGAS/STING/NF-κB axis by tryptanthrin induces microglia polarization toward M2 phenotype and promotes functional recovery in a mouse model of spinal cord injury

The M1/M2 phenotypic shift of microglia after spinal cord injury plays an important role in the regulation of neuroinflammation during the secondary injury phase of spinal cord injury.Regulation of shifting microglia polarization from M1(neurotoxic and proinflammatory type)to M2(neuroprotective and anti-inflammatory type)after spinal cord injury appears to be crucial.Tryptanthrin possesses an anti-inflammatory biological function.However,its roles and the underlying molecular mechanisms in spinal cord injury remain unknown.In this study,we found that tryptanthrin inhibited microglia-derived inflammation by promoting polarization to the M2 phenotype in vitro.Tryptanthrin promoted M2 polarization through inactivating the cGAS/STING/NF-κB pathway.Additionally,we found that targeting the cGAS/STING/NF-κB pathway with tryptanthrin shifted microglia from the M1 to M2 phenotype after spinal cord injury,inhibited neuronal loss,and promoted tissue repair and functional recovery in a mouse model of spinal cord injury.Finally,using a conditional co-culture system,we found that microglia treated with tryptanthrin suppressed endoplasmic reticulum stress-related neuronal apoptosis.Taken together,these results suggest that by targeting the cGAS/STING/NF-κB axis,tryptanthrin attenuates microglia-derived neuroinflammation and promotes functional recovery after spinal cord injury through shifting microglia polarization to the M2 phenotype.

Activation of adult endogenous neurogenesis by a hyaluronic acid collagen gel containing basic fibroblast growth factor promotes remodeling and functional recovery of the injured cerebral cortex

The presence of endogenous neural stem/progenitor cells in the adult mammalian brain suggests that the central nervous system can be repaired and regenerated after injury.However,whether it is possible to stimulate neurogenesis and reconstruct cortical layers II to VI in non-neurogenic regions,such as the cortex,remains unknown.In this study,we implanted a hyaluronic acid collagen gel loaded with basic fibroblast growth factor into the motor cortex immediately following traumatic injury.Our findings reveal that this gel effectively stimulated the proliferation and migration of endogenous neural stem/progenitor cells,as well as their differentiation into mature and functionally integrated neurons.Importantly,these new neurons reconstructed the architecture of cortical layers II to VI,integrated into the existing neural circuitry,and ultimately led to improved brain function.These findings offer novel insight into potential clinical treatments for traumatic cerebral cortex injuries.

Schizonepeta tenuifolia inhibits collagen stimulated platelet function via suppressing MAPK and Akt signaling

The prevalence of cardiovascular diseases(CVDs)is increasing at a rapid pace in developed countries,and CVDs are the leading cause of morbidity and mortality.Natural products and ethnomedicine have been shown to reduce the risk of CVDs.Schizonepeta(S.)tenuifolia is a medicinal plant widely used in China,Korea,and Japan and is known to exhibit anti-inflammatory,antioxidant,and immunomodulatory activities.We hypothesized that given herbal plant exhibit pharmacological activities against CVDs,we specifically explored its effects on platelet function.Platelet aggregation was evaluated using standard light transmission aggregometry.Intracellular calcium mobilization was assessed using Fura-2/AM,and granule secretion(ATP release)was measured in a luminometer.Fibrinogen binding to integrin a_(Ⅱb)β_3,was assessed using flow cytometry.Phosphorylation of mitogen-activated protein kinase(MAPK)signaling molecules and activation of the protein kinase B(Akt)was assessed using Western blot assays.S.tenuifolia,extract potently and significantly inhibited platelet aggregation,calcium mobilization,granule secretion,and fibrinogen binding to integrin a_(Ⅱb)β_3.Moreover,all extracts significantly inhibited MAPK and Akt phosphorylation.S.tenuifolia extract inhibited platelet aggregation and granule secretion,and attenuated collagen mediated GPVI downstream signaling,indicating the potential therapeutic effects of these plant extracts on the cardiovascular system and platelet function.We suggest that S.tenuifolia extract may be a potent candidate to treat platelet-related CVDs and to be used as an antiplatelet and antithrombotic agent.

Thermal vibration of functionally graded porous nanocomposite beams reinforced by graphene platelets

The thermal vibration of functionally graded(FG)porous nanocomposite beams reinforced by graphene platelets(GPLs)is studied.The beams are exposed to the thermal gradient with a multilayer structure.The temperature varies linearly across the thickness direction.Three different types of dispersion patterns of GPLs as well as porosity distributions are presented.The material properties vary along the thickness direction.By using the mechanical parameters of closed-cell cellular solid,the variation of Poisson’s ratio and the relation between the porosity coefficient and the mass density under the Gaussian random field(GRF)model are obtained.By using the Halpin-Tsai micromechanics model,the elastic modulus of the nanocomposite is achieved.The equations of motion based on the Timoshenko beam theory are obtained by using Hamilton’s principle.These equations are discretized and solved by using the generalized differential quadrature method(GDQM)to obtain the fundamental frequencies.The effects of the weight fraction,the dispersion model,the geometry,and the size of GPLs,as well as the porosity distribution,the porosity coefficient,the boundary condition,the metal matrix,the slenderness ratio,and the thermal gradient are presented.

Plasma brain natriuretic peptide, platelet parameters, and cardiopulmonary function in chronic obstructive pulmonary disease

BACKGROUND Chronic obstructive pulmonary disease(COPD)is a chronic respiratory disease with worldwide occurrence and high disability and mortality rate.It occurs mostly in the elderly population with pulmonary heart disease,type II respiratory failure,and other serious complications.AIM To investigate the correlation of plasma brain natriuretic peptide(BNP)and platelet parameters with cardiac function and pulmonary hypertension in patients with COPD and pulmonary heart disease.METHODS From June 2016 to June 2019,52 patients with COPD-pulmonary heart disease(pulmonary heart disease group),30 patients with COPD(COPD group),and 30 healthy individuals(control group)in our hospital were enrolled in the study.The pulmonary heart disease group was further divided into subgroups according to cardiac function classification and pulmonary artery pressure.Plasma BNP and platelet parameters were estimated and compared among each group and subgroup.The correlation of plasma BNP and platelet parameters with cardiac function classification and pulmonary artery pressure was then analyzed.RESULTS In the pulmonary heart disease group,the COPD group,and the control group,the levels of plasma BNP,platelet distribution width(PDW),and mean platelet volume(MPV)showed a decreasing trend(P<0.05),while an increasing trend was found in platelet count(PLT)and plateletcrit(PCT)levels among the three groups(P<0.05).In the pulmonary hypertension mild,moderate,and severe subgroups,the levels of plasma BNP,PDW,and MPV showed an increasing trend(P<0.05),while a decreasing trend was observed in PLT levels(P<0.05);however,PCT levels showed no significant difference among the three subgroups(P>0.05).In the cardiac function grade I,II,III,and IV subgroups,the levels of plasma BNP,PDW,and MPV showed an increasing trend(P<0.05),while a decreasing trend was noted in PLT and PCT levels among the four subgroups(P<0.05).Correlation analysis showed that the levels of plasma BNP,PDW,and MPV in patients with pulmonary heart disease were positively correlated with their pulmonary artery pressure(P<0.05),while PLT was negatively correlated with their pulmonary artery pressure(P<0.05).Moreover,plasma BNP,PDW,and MPV levels were positively correlated with cardiac function grade(P<0.05)of these patients,while PLT and PCT levels were negatively correlated with their cardiac function grade(P<0.05).CONCLUSION Plasma BNP and PLT parameters are significantly correlated with the cardiac function and pulmonary hypertension in patients with COPD and pulmonary heart disease,indicating that these parameters have high clinical relevance in reflecting the health condition of these patients and for guiding their treatment.

Impact of high dose vitamin C on platelet function

AIM To examine the effect of high doses of vitamin C(VitC) on ex vivo human platelets(PLTs).METHODS Platelet concentrates collected for therapeutic or prophylactic transfusions were exposed to:(1) normal saline(control);(2) 0.3 mmol/L VitC(Lo VitC); or(3) 3 mmol/L VitC(Hi VitC, final concentrations) and stored appropriately. The Vit C additive was preservative-free buffered ascorbic acid in water, pH 5.5 to 7.0, adjusted with sodium bicarbonate and sodium hydroxide. The doses of Vit C used here correspond to plasma Vit C levels reported in recently completed clinical trials. Prior to supplementation, a baseline sample was collected for analysis. PLTs were sampled again on days 2, 5 and 8 and assayed for changes in PLT function by: Thromboelastography(TEG), for changes in viscoelastic properties; aggregometry, for PLT aggregation and adenosine triphosphate(ATP) secretion in response to collagen or adenosine diphosphate(ADP); and flow cytometry, for changes in expression of CD-31, CD41 a, CD62 p and CD63. In addition, PLT intracellular Vit C content was measured using a fluorimetric assay for ascorbic acid and PLT poor plasma was used for plasma coagulation tests [prothrombin time(PT), partial thrombplastin time(PTT), functional fibrinogen] and Lipidomics analysis(UPLC ESI-MS/MS).RESULTS VitC supplementation significantly increased PLTs intracellular ascorbic acid levels from 1.2 mmol/L at baseline to 3.2 mmol/L(Lo VitC) and 15.7 mmol/L(Hi VitC, P < 0.05). VitC supplementation did not significantly change PT and PTT values, or functional fibrinogen levels over the 8 d exposure period(P > 0.05). PLT function assayed by TEG, aggregometry and flow cytometry was not significantly altered by Lo or Hi VitC for up to 5 d. However, PLTs exposed to 3 mmol/L VitC for 8 d demonstrated significantly increased R and K times by TEG and a decrease in the α-angle(P < 0.05). There was also a fall of 20 mm in maximum amplitude associated with the Hi VitC compared to both baseline and day 8 saline controls. Platelet aggregation studies, showed uniform declines in collagen and ADP-induced platelet aggregations over the 8-d study period in all three groups(P > 0.05). Collagen and ADP-induced ATP secretion was also not different between the three groups(P > 0.05). Finally, VitC at the higher dose(3 mmol/L) also induced the release of several eicosanoids including thromboxane B2 and prostaglandin E2, as well as products of arachidonic acid metabolism via the lipoxygenases pathway such as 11-/12-/15-hydroxyicosatetraenoic acid(P < 0.05).CONCLUSION Alterations in PLT function by exposure to 3 mmol/L VitC for 8 d suggest that caution should be exerted with prolonged use of intravenous high dose VitC.

Postbuckling analysis of functionally graded graphene platelet-reinforced polymer composite cylindrical shells using an analytical solution approach

An analytical approach is proposed to study the postbuckling of circular cylindrical shells subject to axial compression and lateral pressure made of functionally graded graphene platelet-reinforced polymer composite (FG-GPL-RPC). The governing equations are obtained in the context of the classical Donnell shell theory by the von K′arm′an nonlinear relations. Then, based on the Ritz energy method, an analytical solution approach is used to trace the nonlinear postbuckling path of the shell. The effects of several parameters such as the weight fraction of the graphene platelet (GPL), the geometrical properties, and distribution patterns of the GPL on the postbuckling characteristics of the FG-GPL-RPC shell are analyzed.

Preparation of Functionalized Graphene Nano-platelets and Use for Adsorption of Pb2+ from Solution

Functionalized graphene nano-platelets(FGN) were obtained via treating graphene nanoplatelets(GN) with HNO3, and served as adsorbent for the removal of Pb2+from solutions. We investigated the FGN adsorption capacity for Pb2+at different initial concentrations, varying pH, contact time and temperature. The characterization results of scanning electron microscopy(SEM), thermal analysis(TG/DTG), Fourier transform infrared spectroscopy(FT-IR) and Brunauer-Emmett-Teller(BET) method indicated that FGN layers were thin and possess large specific area with oxygen-containing functional groups grafted onto their surface. Meanwhile, the determined equilibrium adsorption capacity of FGN for Pb2+was 57.765 mg/g and adsorption isotherms well confirmed to Langmuir isotherms models. The results reveals that the FGN has better effect of water treatment.

Preservation of platelet function in patients with cirrhosis and thrombocytopenia undergoing esophageal variceal ligation

Background:Thrombocytopenia is a possible risk factor for bleeding after band ligation of esophageal varices.However,elevated von Willebrand factor(VWF)in cirrhosis improves platelet function and could decrease this risk.Our objective was to assess platelet function in patients with cirrhosis undergoing esophageal variceal ligation(EVL).Methods:The assessment consisted of platelet count,antigen and activity of VWF and VWF-cleaving protease ADAMTS-13 activity,and a platelet adhesion and aggregation test simulating vascular flow in vivo(Impact-RR)prior to EVL.Results:Totally 111 patients were divided into three groups according to platelet count:(1)<50×109/L(n=38,34.2%);(2)50×109/L to 100×109/L(n=47,42.3%);and(3)>100×109/L(n=26,23.4%).No statistically significant difference was found in the aggregate size of platelets[group 1:41.0(31.8–67.3)μm 2;group 2:47.0(33.8–71.3)μm 2;and group 3:47.0(34.0–66.0)μm 2;P=0.60]and no significant correlation was found between aggregate size and platelet count(Spearman r=0.07;P=0.47).Surface coverage was 4.1%(2.8%–6.7%),8.5%(4.0%–10.0%),and 9.0%(7.1%–12.0%)(P<0.001)in groups 1,2 and 3,respectively and correlated with platelet count(Spearman r=0.39;P<0.0001).There was no significant difference between groups in VWF or ADAMTS-13.Post-EVL bleeding occurred in six(5.4%)patients(n=2 in group 1,n=1 in group 2,and n=3 in group 3;P=0.32).Patients with bleeding had higher MELD scores[15.0(11.3–20.3)versus 12.0(10.0–15.0);P=0.025],but no difference was demonstrated for platelet function parameters.Conclusion:Platelet function is preserved even in the presence of thrombocytopenia,including in the patients with post-EVL bleeding.

Effects of omeprazole or pantoprazole on platelet function in non-ST-segment elevation acute coronary syndrome patients receiving clopidogrel

Background: This study evaluated the effect of omeprazole or pantoprazole on platelet reactivity in non-STsegment elevation acute coronary syndrome(NSTE-ACS) patients receiving clopidogrel.Methods: Consecutive patients with NSTE-ACS(n =620) from general hospital of Shenyang Military Command were randomized to the omeprazole or pantoprazole(20mg/d) group(1:1), and received routine dual antiplatelet treatment. Patients' reversion rate of adenosine diphosphate-induced platelet aggregation(ADP-PA) was assessed at baseline, 12 to 24 h after administration of medication, and after 72 h of percutaneous coronary intervention(PCI). The primary endpoint of the study was platelet reactivity assessed with ADP-PA at 30 days after PCI. Adverse events(AEs) were recorded for 30-day and 180-day follow-up periods.Results: There were no significant differences between both the groups in platelet response to clopidogrel at 12–24h after drug administration(54.09%±18.90% vs. 51.62%±19.85%, P=0.12), 72 h after PCI(52.15%±19.45% vs. 49.66%±20.05%, P=0.18), and 30 days after PCI(50.44%±14.54% vs. 48.52%±15.08%, P=0.17). The rate of AEs did not differ significantly between groups during the 30-day(15.2% vs. 14.8%, P=0.91) and 180-day(16.5% vs. 14.5%, P=0.50) follow-up periods after PCI.Conclusion: The addition of omeprazole or pantoprazole to clopidogrel did not restrict the effect of platelet aggregation by reducing the conversion of clopidogrel. Compared with clopidogrel alone, pantoprazole-clopidogrel and omeprazoleclopidogrel combinations did not increase the incidence of adverse clinical events during 30-day and 180-day follow-up periods after PCI.