ObjectiveTo explore the possible mechanisms by which ligustilide （LIG） exerts neuroprotective effects on ischemic stroke （IS） by inhibiting the release of neutrophil extracellular traps （NETs）， promoting blood-brain barrier repair， and alleviating post-ischemic neuroinflammation， thereby providing a new direction for IS treatment. MethodsA middle cerebral artery occlusion （MCAO） model was established in rats. The rats were divided into the sham operation （Sham） group， model （Model） group， low- and high-dose LIG groups （20， 40 mg·kg^-1）， and the NET inhibitor CI-amidine group （CI-amidine， 10 mg·kg^-1）. Drug treatments were administered for 3 days. Neurological injury after ischemia was evaluated by 2，3，5-triphenyltetrazolium chloride （TTC） staining， neurological deficit scoring， and brain index measurement. Flow cytometry and Western blot were used to analyze changes in neutrophil expression. Immunofluorescence was used to observe the fluorescence intensity of the NET marker citrullinated histone H3 （H3Cit）. Western blot was performed to detect the expression of blood-brain barrier tight junction-related proteins and inflammatory factors， including interleukin-18 （IL-18） and interleukin-1β （IL-1β）. ResultsCompared with the Sham group， the Model group exhibited significant brain tissue injury （P<0.05）， significantly increased neutrophil numbers and NET expression （P<0.05）， significantly impaired blood-brain barrier permeability （P<0.05）， and significantly increased expression of inflammatory factors （P<0.05）. Compared with the Model group， both low- and high-dose LIG significantly alleviated brain tissue injury in rats （P<0.01）， inhibited neutrophil numbers and NET expression （P<0.01）， reduced blood-brain barrier damage （P<0.01）， and suppressed the expression of inflammatory factors IL-18 and IL-1β （P<0.01）， thereby ultimately exerting a neuroprotective effect. ConclusionThe neuroprotective effect of LIG in rats with cerebral ischemia-reperfusion injury may be related to inhibition of neutrophils and the NETs induced by them.

ObjectiveTo explore the possible mechanisms by which ligustilide （LIG） exerts neuroprotective effects on ischemic stroke （IS） by inhibiting the release of neutrophil extracellular traps （NETs）， promoting blood-brain barrier repair， and alleviating post-ischemic neuroinflammation， thereby providing a new direction for IS treatment. MethodsA middle cerebral artery occlusion （MCAO） model was established in rats. The rats were divided into the sham operation （Sham） group， model （Model） group， low- and high-dose LIG groups （20， 40 mg·kg^-1）， and the NET inhibitor CI-amidine group （CI-amidine， 10 mg·kg^-1）. Drug treatments were administered for 3 days. Neurological injury after ischemia was evaluated by 2，3，5-triphenyltetrazolium chloride （TTC） staining， neurological deficit scoring， and brain index measurement. Flow cytometry and Western blot were used to analyze changes in neutrophil expression. Immunofluorescence was used to observe the fluorescence intensity of the NET marker citrullinated histone H3 （H3Cit）. Western blot was performed to detect the expression of blood-brain barrier tight junction-related proteins and inflammatory factors， including interleukin-18 （IL-18） and interleukin-1β （IL-1β）. ResultsCompared with the Sham group， the Model group exhibited significant brain tissue injury （P<0.05）， significantly increased neutrophil numbers and NET expression （P<0.05）， significantly impaired blood-brain barrier permeability （P<0.05）， and significantly increased expression of inflammatory factors （P<0.05）. Compared with the Model group， both low- and high-dose LIG significantly alleviated brain tissue injury in rats （P<0.01）， inhibited neutrophil numbers and NET expression （P<0.01）， reduced blood-brain barrier damage （P<0.01）， and suppressed the expression of inflammatory factors IL-18 and IL-1β （P<0.01）， thereby ultimately exerting a neuroprotective effect. ConclusionThe neuroprotective effect of LIG in rats with cerebral ischemia-reperfusion injury may be related to inhibition of neutrophils and the NETs induced by them.

ObjectiveTo investigate the triglyceride-glucose (TyG) index and the level of serum homocysteine (Hcy) in association with the incidence of stroke in type 2 diabetes mellitus (T2DM) patients. MethodsBased on the chronic disease risk factor surveillance cohort in Pudong New Area, Shanghai, excluding those with stroke in baseline survey, T2DM patients who joined the cohort from January 2016 to October 2020 were selected as the research subjects. During the follow-up period, a total of 318 new-onset ischemic stroke patients were selected as the case group, and a total of 318 individuals matched by gender without stroke were selected as the control group. The Cox proportional hazards regression model was used to adjust for confounding factors and explore the serum TyG index and the Hcy biochemical indicator in association with the risk of stroke. ResultsThe Cox proportional hazards regression results showed that after adjusting for confounding factors, the risk of stroke in T2DM patients with 10 μmol·L⁻¹-¹ and Hcy>15 μmol·L⁻¹ was 1.532 times (95%CI: 1.017‒2.309 times, P=0.041) and 1.738 times (95%CI: 1.119‒2.699 times, P=0.014) higher respectively, compared to T2DM patients with Hcy≤10 μmol·L⁻¹. T2DM patients with TyG>9.074 had 1.396 times higher risk of stroke (95%CI: 1.091‒1.787, P=0.008) compared to those with TyG≤9.074. The study found that urea and α1-antitrypsin (α1-AT) were independent risk factors for the incidence of stroke in T2DM patients. For every unit increase in urea andα1-AT, the risk of stroke in T2DM patients increased by 233.6% (HR=3.336, 95%CI: 1.588‒7.009, P=0.001) and 11.3% (HR=1.113, 95%CI: 1.028‒1.205, P=0.008), respectively. Cumulative risk curves showed that Hcy>10 μmol·L⁻¹ and TyG>9.074 accelerated the time to stroke occurrence in T2DM patients. ConclusionElevated levels of Hcy>10 μmol·L⁻¹ and a higher TyG index are risk factors for stroke in T2DM patients. Effective interventions for Hcy and TyG should be conducted for diabetic patients to reduce the incidence of stroke.

BACKGROUND: Arsenic trioxide (ATO) is indicated as a broad-spectrum medicine for a variety of diseases, including cancer and cardiac disease. While the role of ATO in hepatic ischemia/reperfusion injury (HIRI) has not been reported. Thus, the purpose of this study was to identify the effects of ATO on HIRI. METHODS: In the present study, we established a 70% hepatic warm I/R injury and partial hepatectomy (30% resection) animal models in vivo and hepatocytes anoxia/reoxygenation (A/R) models in vitro with ATO pretreatment and further assessed liver function by histopathologic changes, enzyme-linked immunosorbent assay, cell counting kit-8, and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) assay. Small interfering RNA (siRNA) for extracellular signal-regulated kinase (ERK) 1/2 was transfected to evaluate the role of ERK1/2 pathway during HIRI, followed by ATO pretreatment. The dynamic process of autophagic flux and numbers of autophagosomes were detected by green fluorescent protein-monomeric red fluorescent protein-LC3 (GFP-mRFP-LC3) staining and transmission electron microscopy. RESULTS: A low dose of ATO (0.75 μmol/L in vitro and 1 mg/kg in vivo ) significantly reduced tissue necrosis, inflammatory infiltration, and hepatocyte apoptosis during the process of hepatic I/R. Meanwhile, ATO obviously promoted the ability of cell proliferation and liver regeneration. Mechanistically, in vitro  studies have shown that nontoxic concentrations of ATO can activate both ERK and phosphoinositide 3-kinase-serine/threonine kinase (PI3K-AKT) pathways and further induce autophagy. The hepatoprotective mechanism of ATO, at least in part, relies on the effects of ATO on the activation of autophagy, which is ERK-dependent. CONCLUSION Low, non-toxic doses of ATO can activate ERK/PI3K-AKT pathways and induce ERK-dependent autophagy in hepatocytes, protecting liver against I/R injury and accelerating hepatocyte regeneration after partial hepatectomy.
Animals ; Arsenic Trioxide ; Autophagy/physiology* ; Reperfusion Injury/prevention & control* ; Mice ; Male ; Proto-Oncogene Proteins c-akt/physiology* ; Arsenicals/therapeutic use* ; Oxides/therapeutic use* ; Liver/metabolism* ; Extracellular Signal-Regulated MAP Kinases/metabolism* ; Mice, Inbred C57BL

Objective To explore the association of the magnitude of systolic blood pressure reduction(SBPr)with post-procedure 24 h symptomatic intracranial hemorrhage(sICH)and 90-day clinical outcomes in patients with successful endovascular thrombectomy(EVT).Methods Consecutively registered patients with EVT caused by anterior circulation large vessel occlusion stroke(LVOS)in the First Affiliated Hospital of Wannan Medical College(Yijishan Hospital)between July 2015 and April 2023 and patients with successful reperfusion were analyzed.Demographic data,medical history(hypertension,diabetes),the trial of Org 10172 in acute stroke treatment(TOAST)classification,the baseline National Institutes of Health Stroke Scale(NIHSS)score and the baseline Alberta stroke early CT(ASPECT)score of patients were collected.And procedure related parameters(including time from onset to puncture,time from onset to reperfusion,occluded site[internal carotid artery,M1 segment of middle cerebral artery,M2 segment of middle cerebral artery],collateral circulation status[determined based on preoperative occluded angiography showing the range of collateral circulation in the occluded vessel area,defined as good collateral circulation with a reflux range of ≥ 50％and poor collateral circulation with a reflux range of＜50％]),immediate postoperative reperfusion status(evaluated using the modified thrombolysis for cerebral infarction[mTICI]grading,successful reperfusion defined as mTICI grading of 2b-3),24 hours sICH,and 90 days clinical outcomes(evaluated using the modified Rankin scale score at 90days after EVT,with a score ≤ 2indicating a good prognosis and a score＞2indicating a poor prognosis).SBPr was defined as(baseline SBP-mean SBP)/baseline SBP x 100％.According to the the magnitude of SBPr,SBPr is divided into 5 categories(＜-10％,-10％-10％,＞10％-20％,＞20％-30％and＞30％).Based on the clinical outcomes at 90 days and the occurrence of sICH at 24 hours after EVT,patients were divided into a good prognosis group and a poor prognosis group,as well as an sICH group and a non-sICH group.The relationship between SBPr and postoperative 90 days clinical prognosis or sICH was analyzed using a binary Logistic regression model.Subgroup analysis was conducted based on a history of hypertension(yes and no),continuous intravenous hypotensive therapy(yes and no),baseline ASPECT scores(3-5 and 6-10),and collateral circulation status(good and bad).Using a restricted cubic plot to depict the relationship between SBPr and sICH and clinical prognosis at 90days.Results(1)In total,731 patients were included.The median age was 71(62,77)years and 424(58.0％)were men.The median baseline NIHSS score was 14(12,18),the median baseline ASPECT was 9(7,10),405(55.4％)patients achieved 90-day modified Rankin scale score 0-2,and 35 patients(4.8％)developed sICH.(2)Multivariate analysis showed that the older age(OR,1.036,95％CI 1.017-1.056),the higher baseline NIHSS score(OR,1.095,95％CI1.049-1.144),the lower baseline ASPECT score(OR,0.704,95％CI 0.636-0.780),diabetes(OR,1.729,95％CI 1.084-2.758),bad collateral circulation(good collateral circulation vs.bad collateral circulation,OR,0.481,95％CI 0.332-0.696)and SBPr＞30％(SBPr-10％-10％as a reference,OR,2.238,95％CI 1.230-4.071),the higher the risk of poor clinical outcomes at 90 days(all P＜0.05).Continuous intravenous hypotensive therapy is a risk factor for postoperative 24 h sICH(OR,2.278,95％CI 1.047-4.953;P=0.038),while SBPr 20％-30％is associated with a lower risk of postoperative 24 h sICH(SBPr-10％-10％as a reference,OR,0.362,95％CI0.131-0.998;P=0.049).(3)The restrictive cube plot shows that there is a U-shaped relationship between SBPr after EVT and poor clinical outcomes at 90 days,while there is a nearly linear relationship with the occurrence of sICH.The more SBP reduction,the lower the incidence of sICH.(4)In the subgroup analyses,in the non-hypertension history and the good collateral circulation group,SBPr＞30％has a higher risk of poor clinical outcomes compared to SBPr-10％-10％(OR and 95％CI were 2.921[1.000-8.528]and 2.363[1.078-5.183],respectively,with P=0.05 or P＜0.05);After EVT,the group receiving continuous intravenous hypotensive therapy and the baseline ASPECT score 6-10 groups showed a significant correlation between SBPr＞30％and poor clinical outcomes at 90 days(SBPr-10％-10％as a reference,OR and 95％CI were 2.646[1.168-5.993]and 2.481[1.360-4.527],respectively,with P＜0.05).The correlation between SBPr and lower incidence of sICH was only found in the subgroup of poor collateral circulation(SBPr-10％-10％as a reference,SBPr＞20％-30％:OR,0.133,95％CI 0.027-0.652;SBPr＞30％:OR,0.104,95％CI 0.013-0.864;all P＜0.05).Conclusions Among patients who achieved successful reperfusion with EVT,SBPr might be related to a worse functional outcome at 90 days and sICH 24 h after operation.However,the relationship may exhibit significant heterogeneity across different subgroups.Baseline ASPECT score,history of hypertension,collateral circulation,and the use of continuous venous hypertension after EVT have been highlighted in individualized blood pressure management after EVT.

Platelets have long been recognized as key players in hemostasis and thrombosis; however, there is growing evidence that they are also involved in cancer. Preclinical and clinical studies have shown that platelets can promote tumorigenesis and metastasis through various crosstalks between platelets and cancer cells. Platelets play an active role in all stages of tumorigenesis, including tumor growth, tumor cell extravasation, and metastasis. In addition, thrombocytosis in cancer patients is associated with poor patient survival. Platelets are also well-placed to coordinate local and distant tumor-host interactions due to the a- bundance of microparticles and exosomes. Therefore, antitumor drugs targeting platelets have great development and application prospects. The following will review the research progress of anti-tumor drugs targeting platelets.

Objective To investigate the influencing factors for acute multiple vessels occlusion(MVO)and its impact on the prognosis of patients with anterior circulation acute large vessel occlusion stroke(ALVOS)who achieved successful recanalization after endovascular treatment(EVT).Methods Patients with anterior circulation ALVOS who received successful EVT at the Yijishan Hospital of Wannan Medical College between July 2015 and April 2023 were retrospectively analyzed.Baseline data,including age,sex,onset-to-puncture time(OTP),onset-to-recanalization time(OTR),medical history(including atrial fibrillation,diabetes,hypertension),alcohol and smoking history,admission blood pressure(systolic and diastolic),Alberta stroke program early CT score(ASPECTS),National Institutes of Health stroke scale(NIHSS)score,trial of Org 10172 in acute stroke treatment(TOAST)classification(atherosclerotic type,cardioembolic type,and other etiology types),and 90-day modified Rankin scale(mRS)score were collected.Collateral circulation was assessed based on the degree of contrast agent reflux observed in the occluded arterial supply area during delayed DSA,and patients were classified into poor and good collateral circulation groups.Malignant cerebral edema was defined as a midline shift of ≥5 mm on the follow-up CT scan performed on day 3 post-surgery.The primary endpoint(efficacy indicator)was the 90-day mRS score,with mRS score≤ 2 considered as a good prognosis and mRS score＞2 considered as a poor prognosis.The secondary endpoint(safety indicator)was the 90-day mortality rate.All patients were divided into MVO and non-MVO groups based on whether they had single or multiple intracranial vessel occlusions.Acute MVO was defined as the detection of acute occlusion of other large or medium vessels,in addition to the main vessels(internal carotid artery or M1/M2 segments of the middle crebral artery[MCA]),in CT angiography,MR angiography,or DSA,resulting in ischemia in brain regions distinct from the main occlusion area.Factors that showed statistically significant differences in univariate analysis were further analyzed using multivariate Logistic regression to identify the risk factors for the occurrence of acute MVO and the factors associated with the prognosis of ALVOS patients.Results A total of 846 patients with ALVOS were included,with ages ranging from 26 to 94 years(mean age[69±11]years).The proportion of male patients was 57.2％(484/846).The median admission ASPECTS was 8(7,9)and the median admission NIHSS score was 14(12,18).The incidence of malignant cerebral edema at 3 days post-surgery was 13.4％(112/835),and the 90-day mortality rate was 19.1％(162/846).(1)Among the 846 ALVOS patients,810(95.7％)were in the non-MVO group and 36(4.3％)were in the MVO group.Univariate analysis showed significant differences between the MVO and non-MVO groups in terms of atrial fibrillation,malignant cerebral edema,admission ASPECTS,admission NIHSS scores,TOAST classification,collateral circulation,rate of complete recanalization,and 90-day poor prognosis rate(all P＜0.05).However,there was no statistically significant difference in 90-day mortality between the two groups(P=0.193).Multivariate Logistic regression analysis showed that TOAST classification of cardioembolic type(OR,16.089,95％CI 1.835-141.061,P=0.012)and other etiology types(OR,9.768,95％CI 1.078-88.540,P=0.043)were associated with the occurrence of MVO.(2)Among the 846 ALVOS patients,445 had a good prognosis at 90days,and 401 had a poor prognosis.Univariate analysis showed that,compared to the good prognosis group,the poor prognosis group had a lower proportion of males and smokers,and a higher proportion of patients with older age,higher baseline systolic blood pressure,hypertension,diabetes,and atrial fibrillation(all P＜0.01).Additionally,the poor prognosis group had higher admission NIHSS scores(P＜0.01),lower admission ASPECTS,lower rates of good collateral circulation and complete recanalization,higher rates of malignant cerebral edema and MVO,and statistically significant differences in TOAST classification distribution(all P＜0.01).Multivariate Logistic regression analysis showed that MVO was associated with poor 90-day prognosis in ALVOS patients after EVT(OR,3.368,95％CI 1.149-9.878,P=0.027).Furthermore,older age(OR,1.045,95％CI 1.025-1.066),diabetes(OR,1.719,95％CI 1.080-2.734),higher baseline systolic blood pressure(OR,1.012,95％CI 1.004-1.019),lower admission ASPECTS(OR,0.746,95％CI 0.674-0.826),higher admission NIHSS score(OR,1.115,95％CI 1.070-1.162),without immediate postoperative complete recanalization(OR,0.413,95％CI 0.290-0.592),poor collateral circulation(OR,0.594,95％CI 0.415-0.851),and malignant cerebral edema(OR,6.191,95％CI 3.026-12.670)were all associated with poor 90-day prognosis after EVT in ALVOS patients(all P＜0.05).Conclusions The TOAST classification of cardioembolic type and other etiology types is associated with MVO.MVO is a risk factor for poor outcomes after successful EVT in ALVOS patients.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

OBJECTIVES: Venous thromboembolism is a highly prevalent condition after polytrauma, and recognized as an important factor contributing to poor prognosis. The aim of this study was to investigate the risk factors for lower extremity deep venous thrombosis (LEDVT) in a severely traumatized population and to evaluate their predictive value for LEDVT. METHODS: This was a retrospective, single-center observational study. All subjects were severely traumatized patients who were admitted to the Traumatic Intensive Care Unit from January 2021 to May 2024. Based on Doppler ultrasound findings of both lower extremities from the time of injury to 30 days post-injury, patients who developed LEDVT were enrolled in the LEDVT group, and those who did not develop LEDVT were enrolled in the NLEDVT group. Demographic, clinical, and laboratory data were collected upon admission. Multivariable logistic regression analysis was performed to identify risk factors for LEDVT. Receiver operating characteristic (ROC) curve was used to evaluate the overall fit of the final model. RESULTS: There were 56 patients enrolled in the LEDVT group and 81 patients in the NLEDVT group.Age, Aggregate Index of Systemic Inflammation (AISI), Systemic Inflammation Response Index (SIRI), ICU length of stay, and albumin were identified as independent risk factors for LEDVT (all P < 0.05). The area under their ROC curves were 0.604, 0.657, 0.694, 0.668, and 0.405, respectively. Combined model for early clinical prediction of LEDVT in severely traumatized patients by age, SIRI, AISI, and albumin resulted in an area under the ROC curve of 0.805 (95%CI: 0.73-0.88, SE = 0.037). CONCLUSIONS The combination of age, SIRI, AISI, and albumin has a predictive value for LEDVT in severely traumatized patients.
Humans ; Venous Thrombosis/blood* ; Male ; Female ; Retrospective Studies ; Adult ; Lower Extremity/blood supply* ; Middle Aged ; Inflammation ; Wounds and Injuries/blood* ; Risk Factors ; Predictive Value of Tests ; ROC Curve

Objective:To summarize the clinical features of out-of-hospital extracorporeal cardiopulmonary resuscitation(ECPR) patients and analyze the factors associated with discharge survival.Methods:The data of 54 patients with ECPR in the Emergency Center of the Second Hospital Affiliated to Zhejiang University School of Medicine from January 2020 to December 2023 were analyzed. Patients were divided into the survival group and death group based on their survival status within 30 days of discharge. Kaplan Meier method was used to draw the survival curve, and COX regression analysis was used to analyze the relevant factors of survival.Results:(1) A total of 54 patients with ECPR were included in this study. 17 (31.5%) cases were discharged alive, of which 10 (58.8%) had a good neurological prognosis, while 37 case (68.5%) died.(2) Kaplan-Meier survival analysis showed that patients who received first-witness CPR, had a lower-extremity perfusion line established, underwent IABP, achieved ROSC, had normal pH, and had an initial pupillary light reflex had a longer median survival time ( P < 0.05). (3) Univariate COX regression analysis showed that statistically differences in survival time among patients with ECMO times, hypoperfusion times, initial pupil sizes, and APACHEⅡ scores ( P < 0.05); (4) Multivariate COX regression analysis showed that APACHEⅡ score, initial pupil size, and IABP were independent predictors of survival of patients discharged from the hospital with emergency ECPR; (5) The concordance index of the COX regression model was 0.921. Conclusions:The survival model demonstrates good predictive accuracy. Healthcare professionals can use the APACHEⅡscore and initial pupil size on admission as important reference indicators to assist in determining patient prognosis, and to timely initiate IABP treatment, in conjunction with the patient’s condition, to improve the survival rate of patients discharged from the hospital.