Background: High-mobility group box protein 1 (HMGB1) is a chromatin-binding protein involved in arthritis, ischemia, sepsis, atherosclerosis, neurodegenerative disorders, meningitis, and cancer. HMGB1 exhibits dual roles in cancer, acting as either a tumor suppressor or oncoprotein depending on context. Objective: This research aimed to elucidate HMGB1’s functional significance in cutaneous squamous cell carcinoma (cSCC). Methods: We overexpressed HMGB1 in cSCC cell lines using recombinant adenovirus and examined its effects on cell proliferation, colony formation, and cell migration. Results: Immunohistochemical analysis revealed elevated HMGB1 expression levels in cSCC tissue relative to normal epidermis. To assess the influence of HMGB1, we employed recombinant adenoviruses expressing HMGB1 to transduce SCC cell lines (SCC12 and SCC13). Enhanced HMGB1 expression significantly promoted cellular proliferation and colony formation capacity.Notably, HMGB1 overexpression elevated the levels of proliferation regulators, including P63, SOX2, CDK4 and CDK6. Furthermore, HMGB1 overexpression substantially enhanced tumor invasiveness, accompanied by upregulation of epithelial-mesenchymal transition (EMT) biomarkers. Mechanistically, overexpression of HMGB1 enhanced transforming growth factor-β signaling by increasing phosphorylation of SMAD2/3, the key mediators of EMT. Conclusion These data imply that HMGB1 acts as a tumor-promoting factor in cSCC.

Objective: To compare the effects of eccentric cycling (ECC), concentric cycling (CON), and standard care (CTL) on cardiopulmonary capacity, respiratory health, and quality of life (QoL) in patients with chronic kidney disease (CKD). Methods: Thirty-one CKD patients were divided into the CTL, CON, and ECC groups. The CON and ECC groups participated in 8-week, 24-session cycling programs. Outcomes were assessed through cardiopulmonary exercise tests, respiratory function tests, and the 36-Item Short Form Survey Instrument questionnaire. Results: The ECC group achieved significant improvements in maximal oxygen uptake, while the CTL group showed a decline. For oxygen uptake efficiency slope, significant changes were observed only in the ECC group, with a group-by-time interaction effect compared to CTL. Furthermore, the ECC group demonstrated the most significant increase in diaphragm movement and a significant increase in diaphragm thickness, with comparisons indicating that ECC outperformed both CTL and CON. Regarding QoL, the ECC group exhibited significantly greater improvements in Physical Component Summary and Mental Component Summary, with statistically significant differences compared with the CTL and CON groups. Conclusion ECC is a low-effort, high-benefit exercise modality that significantly enhances cardiopulmonary fitness, respiratory function, and QoL in patients with CKD.

ObjectiveAs a common lifestyle habit, alcohol consumption has a controversial association with the onset of Parkinson’s disease (PD). To demonstrate the correlation between alcohol consumption and PD and to identify associated genes, we integrated findings from clinical surveys, genomics, transcriptomics, and animal experiments. MethodsWe investigated the alcohol consumption rates (including both before and after disease onset) among 244 PD patients in China and 177 PD patients from the U.S. NHANES database. Mendelian randomization (MR) analysis was performed using genome-wide association study (GWAS) data for three alcohol-related traits and seven PD-related datasets from the MRC IEU OpenGWAS database. Transcriptomic data from the substantia nigra of PD patients were obtained from three GEO datasets (GSE7621, GSE20141, and GSE49036) to analyze RIT2 gene transcription. Finally, three groups of animal experiments (water/20% ethanol/20% liquor, with 4 C57BL/6J mice per group) were conducted to examine changes in brain RIT2 gene expression and transcriptomic profiles following alcohol consumption. ResultsThe alcohol consumption rates among PD patients in China and the U.S. (9%-18.87%) were significantly lower than the general population rates of 15%-45% in their respective regions (P<0.001), suggesting a possible negative association between alcohol consumption and PD. Subsequently, in 21 bidirectional MR analyses using 3 alcohol-related GWAS datasets and 7 PD-related GWAS datasets, the forward MR analyses (alcohol intake as exposure, PD as outcome) yielded 12 negative associations (OR_IVW<1) and 9 positive associations (OR_IVW>1). Among these, only two negative associations reached statistical significance: alcohol intake frequency (OR_IVW=0.75, 95% CI: 0.60-0.93, P=0.010) and alcohol consumption (OR_IVW=0.20, 95% CI: 0.05-0.83, P=0.026). The forward MR analysis (alcohol intake→PD) identified 235 SNPs, annotated to 316 genes, while the reverse MR analyses (PD→alcohol intake) identified 37 SNPs, annotated to 53 genes. Notably, only the RIT2 gene appeared in both the forward and reverse MR analyses (alcohol intake→PD: rs28597806, rs8083110; PD→alcohol intake: rs4588066). RIT2 is selectively expressed in the human brain (FPKM: 5.259±2.103), with low or no expression in peripheral tissues (FPKM: <1). Analysis of three human substantia nigra transcriptomic datasets revealed a decreasing trend in RIT2 gene expression in PD patients (GSE20141 array signal: 3.49±1.23 vs. 2.33±0.87, P=0.044). Animal experiments demonstrated that administration of 20% ethanol or 20% liquor (approximately 8% ethanol) stimulated a >2-fold upregulation of RIT2 gene expression in the mouse brain. Furthermore, transcriptomic sequencing revealed that the two alcohol-treated groups exhibited 96 (20% ethanol vs. water control) and 4 (20% liquor vs. water control) differentially expressed genes, respectively, indicating that low-dose alcohol consumption can achieve RIT2 upregulation while minimizing impact on other brain genes. In addition to its anti-infective effects, low-dose alcohol consumption primarily influences signaling pathways related to neurodegenerative diseases such as PD and Prion diseases. ConclusionAlcohol consumption is generally considered as a harmful lifestyle habit. However, some studies have also shown a lower risk of mortality among individuals who consume low doses of alcohol (100 g/week of ethanol) or drink occasionally. Currently, one of the research focuses on alcohol consumption is whether the human body can benefit from low-dose alcohol intake. This study provides new evidence supporting a negative association between alcohol consumption and PD, and for the first time, through MR analysis, identifies the RIT2 gene as a potential mediator of the effect of alcohol consumption on PD. RIT2 is selectively expressed in the human brain. Building upon existing evidence indicating downregulated RIT2 gene expression in PD pathogenesis, our experiments confirm that low-dose alcohol consumption can upregulate RIT2 expression in the brain. In brief, alcohol consumption may suppress the pathogenesis of PD by upregulating RIT2 expression in the substantia nigra. China is facing a serious problem of population aging. This study offers important insights for long-term PD prevention and treatment strategies, with the aim of benefiting more potential PD patients through lifestyle modifications, thereby improving the quality of life of the aging population and reducing the economic burden on healthcare.

Objective To analyze the incidence rate and risk factors of atrial fibrillation (AF) in elderly patients with chronic obstructive pulmonary disease (COPD). Methods A total of 392 patients with COPD in the hospital were selected from December 2020 to December 2024. Patients' data (medical history, echocardiographic data, etc.) were recorded. The incidence rate of AF in patients was recorded and the patients were grouped according to whether or not they developed AF. The differences were compared between the two groups, and the risk factors of AF occurrence in elderly patients with COPD were analyzed. Results Among the 392 patients with COPD, 127 cases (32.40%) met the diagnostic criteria of AF. There were statistically significant differences in age, pulmonary infection, heart failure, diabetes, smoking history, disease duration, LAD, severe renal insufficiency and coronary heart disease between the AF group and the non-AF group (P<0.05). Multivariate logistic regression analysis suggested that age, pulmonary infection, heart failure, diabetes mellitus, smoking history, disease course, LAD, severe renal insufficiency and coronary heart disease were all risk factors for elderly patients with COPD (OR=1.129, 4.246, 3.955, 4.125, 2.038, 1.112, 1.102, 4.397, and 3.865, P<0.05). Conclusion The incidence rate of AF is high in elderly patients with COPD. Age, pulmonary infection, heart failure, diabetes mellitus, smoking history, course of disease, LAD, severe renal insufficiency, and coronary heart disease are all risk factors for AF.

ObjectiveMigraine is a leading neurological disorder and the fourth most common cause of years lived with disability worldwide, affecting nearly 116 million individuals. Although pharmacological treatments are available, their efficacy is often limited by side effects and variable response rates. Repetitive transcranial magnetic stimulation (rTMS) over the dorsolateral prefrontal cortex (DLPFC) offers a safe, non-invasive alternative for migraine management. However, the neurophysiological mechanisms, particularly how rTMS modulates local cortical excitability and distributed pain-related circuits, remain poorly understood. Elucidating these mechanisms is essential for optimizing treatment protocols and improving clinical outcomes. MethodsThis study employed concurrent transcranial magnetic stimulation and electroencephalography (TMS-EEG) to investigate neuroplastic and neurocircuitry mechanisms of DLPFC-rTMS in migraine. Study 1 compared 30 migraineurs and 28 healthy controls to identify abnormalities in TMS-evoked potentials (TEPs) and significant current density (SCD) within sensory-discriminative regions including the primary somatosensory cortex (S1) and posterior insula (pINS), cognitive-affective regions including the anterior insula (aINS) and midcingulate cortex (MCC), and a descending modulatory region, the periaqueductal gray (PAG). Study 2 used a single-blind, crossover, sham-controlled design in 34 healthy participants. Each participant received both active (10 Hz, 80% RMT, 1 500 pulses) and sham DLPFC-rTMS in counterbalanced order. TMS-EEG and cold pain tolerance were assessed before and after each session. ResultsIn Study 1, migraineurs showed a significantly less negative N120 amplitude compared to healthy controls (P=0.027, Cohen’s d=0.60), indicating local intracortical disinhibition. No group differences were observed for N40, P60, or P180 components. At the source level, migraineurs exhibited significantly higher SCD in the S1, pINS, aINS, and MCC (allQ<0.05), but not in the ventroposterior thalamus (vpTHAL), mediodorsal thalamus (mdTHAL), or PAG. In Study 2, active rTMS significantly reduced SCD from pre- to post-stimulation in the S1, aINS, and MCC (all Q<0.05). Sham stimulation also reduced SCD in the S1 (Q<0.05) but not in the aINS or MCC. Although no significant group-level analgesic effect was observed between active and sham conditions (P=0.107), correlation analyses revealed that greater SCD reductions in the S1 and MCC were significantly associated with higher post-rTMS pain tolerance (R=-0.487 and -0.495, both Q<0.01) and larger improvements in pain tolerance(R=-0.487 and -0.451, both Q<0.05). No such correlations were found following sham stimulation, suggesting that the behavioural relevance of neural changes is specific to active rTMS. ConclusionThis study provides novel evidence that migraineurs exhibit both local neuroplastic abnormalities (reduced N120 amplitude) and hyperactivity in key pain-processing regions (S1, pINS, aINS, MCC). A single session of DLPFC-rTMS reduced hyperactivity in the aINS, MCC, and S1. Notably, greater reductions in the S1 and MCC were associated with improved pain tolerance. These findings identify distinct cortical circuitries, particularly within the cognitive-affective pain network, that may serve as potential biomarkers for optimizing rTMS treatment in migraine and other chronic pain conditions. Future studies should validate these results in patient populations experiencing spontaneous migraine attacks and explore multi-session or accelerated rTMS protocols.

To formulate an expert consensus on the principles of preoperative hair removal and provide scientific guidance for standardized removal of hair before surgical procedures so as to reduce the incidence of surgical site infections.METHODS Led by the Hospital Management Institute of National Health Commission of the People's Republic of China,this consensus was reached with the joint efforts from the expects of relevant fields such as surgeries,interventional therapies,nursing,and infection prevention and control.The consensus facilitates the classification and evaluation of literatures by following the evidence grade formulated by Oxford Evidence-based Medicine Center and focuses on the association of preoperative hair removal with surgical site infection,it reaches the evidence grade of expert consensus and recommendation intensity by integrating with discussions on meetings and clinical experience of the expects from relevant fields.RESULTS A total of 6 items of consensus were reached by summarizing the latest evidence on the aspects including the indications for preoperative hair removal,tools,range,timing and places.CONCLUSION The consensus,to some extent,make supplements to and complete the exiting regulations and standards.It provides guidance for the medical institutions to carry out the preoperative hair removal.

Aim To explore the mechanism of luteolin in alleviating hepatic fibrosis.Methods C57BL/6 mice were randomly divided into the control group,CCl4 group,silybin group(100 mg·kg-1)and luteo-lin group(100 mg·kg-1).After 10-week modeling and 2-week treatment,the serum levels of aminotrans-ferase and liver histopathology were examined.Hepatic fibrosis and autophagy-related gene expression were as-sessed using immunohistochemistry and immunofluores-cence.Human hepatic stellate cell line(LX2)was cultured and divided into control,TGF-β1(10 mg·L-1),TGF-β1+silybin(40 μmol·L-1),TGF-β1+luteolin(40 μmol·L-1).Fibrotic and autophagy-re-lated markers were analyzed using quantitative real-time PCR,Western blot,immunofluorescence and MDC staining.Results Compared with the CCl4 group,the treatment groups showed significantly improved liver function and reduced hepatic fibrosis,with markedly downregulated COL1A1 and α-SMA expression,and luteolin demonstrated superior efficacy.Compared with TGF-β1 group,luteolin treatment significantly de-creased mRNA levels of COL1A1,ACTA2 and MAP1LC3B,while increasing the mRNA level of SQSTM1,the protein levels of COL1A1 and α-SMA de-creased,p62 was enhanced,the LC3Ⅱ/Ⅰ ratio was downregulated,and autophagy was reduced.These effects of luteolin were reversed by autophagy inducer rapamycin.Conclusion Luteolin alleviates liver fi-brosis by decreasing the autophagy of hepatic stellate cells.

To formulate an expert consensus on the principles of preoperative hair removal and provide scientific guidance for standardized removal of hair before surgical procedures so as to reduce the incidence of surgical site infections.METHODS Led by the Hospital Management Institute of National Health Commission of the People's Republic of China,this consensus was reached with the joint efforts from the expects of relevant fields such as surgeries,interventional therapies,nursing,and infection prevention and control.The consensus facilitates the classification and evaluation of literatures by following the evidence grade formulated by Oxford Evidence-based Medicine Center and focuses on the association of preoperative hair removal with surgical site infection,it reaches the evidence grade of expert consensus and recommendation intensity by integrating with discussions on meetings and clinical experience of the expects from relevant fields.RESULTS A total of 6 items of consensus were reached by summarizing the latest evidence on the aspects including the indications for preoperative hair removal,tools,range,timing and places.CONCLUSION The consensus,to some extent,make supplements to and complete the exiting regulations and standards.It provides guidance for the medical institutions to carry out the preoperative hair removal.

Aim To investigate the effect of oroxylin A(OA)on apoptosis in Ishikawa cell line of endometrial cancer and the underlying mechanism through the phosphatidylinositol-3 kinase/protein kinase B(PI3K/AKT)signaling pathway.Methods Ishikawa cells were treated with different concentrations of OA(0,4,8,10,12,and 20 μmol·L-1)for 24 h-72 h,the cell viability was detected by CCK-8 assay,apoptosis was detected by flow cytometry,and the protein ex-pression levels of B-cell lymphoma-2(Bcl-2),Bcl-2-associated X protein(Bax),PI3K/AKT,recombinant cytochrome P450 1B1(CYP1B1),and catechol-O-methyltransferase(COMT)were detected by Western blot technique.Results OA inhibited the prolifera-tion of Ishikawa cells in a concentration-and time-de-pendent manner.Compared with the blank control group,the expression of Bax protein increased signifi-cantly,while the expression of Bcl-2 protein decreased significantly with the increase of OA concentration.The expression of COMT protein increased significant-ly,while the expression of CYP1B1 protein decreased significantly.PI3K/AKT:IGF-1(PI3 K agonist)sup-plementation reversed the effect,the expression of COMT protein significantly decreased,and the expres-sion of CYP1B1 protein significantly increased.Con-clusions OA exerts anti-tumor effects in Ishikawa cells of endometrial cancer,which may be related to cell apoptosis mediated by the inhibition of the PI3K/AKT signaling pathway.

Objective:To compare the efficacy of different doses of tranexamic acid (TXA) for traumatic hemorrhagic shock (THS) in the early phase of trauma following acute exposure to high altitude in rabbits.Methods:Twenty-five healthy male New Zealand rabbits were randomly divided into plain control group ( n=5) and acute high-altitude THS group ( n=20) according to the random number table method. The plain control group did not undergo THS modeling throughout the experiment while the acute high-altitude THS group was raised in a hypoxia simulation chamber with a volume fraction of 10% for 3 days to establish the THS model. Based on the different doses of TXA administered intravenously at 30 minutes after THS modeling, the acute high-altitude THS group was further divided into four subgroups: acute high-altitude THS+0 mg/kg TXA subgroup, acute high-altitude THS+45 mg/kg TXA subgroup, acute high-altitude THS+90 mg/kg TXA subgroup and acute high-altitude THS+135 mg/kg TXA subgroup, with 5 rabbits in each. The vital signs [mean arterial pressure (MAP), heart rate, rectal temperature] and blood cell counts [red blood cell count (RBC), platelet count (PLT)], 4 coagulation parameters [fibrinogen (FIB), D-dimer, activated partial thromboplastin time (APTT), prothrombin time (PT)], thromboelastography [clotting reaction time (R value), clot formation time (K value), maximum amplitude (MA value)], syndecan-1, inflammatory factors [interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α)], and plasminogen activator inhibitor-1 (PAI-1) were recorded before blood loss, at 30 minutes and 120 minutes after blood loss. At 6 hours after THS, the lungs, terminal ileum, and kidneys of the rabbits were collected to observe tissue damage, and the wet/dry weight ratio (W/D) and total water content (TLW) of the lung tissue were measured. Results:(1) Vital signs: Before blood loss, there were no significant differences in MAP, heart rate, or rectal temperature between the acute high-altitude THS subgroups and the plain control group ( P>0.05). At 30 minutes and 120 minutes after blood loss, the acute high-altitude THS subgroups exhibited significantly lower MAP, heart rate, and rectal temperature compared to those in the plain control group ( P<0.05). No significant differences were observed in MAP, heart rate or rectal temperature among the acute high-altitude THS subgroups at any time point ( P>0.05). In the acute high-altitude THS subgroups, MAP, heart rate and rectal temperature were significantly decreased at 30 minutes and 120 minutes after blood loss compared to those before blood loss ( P<0.05); At 120 minutes after blood loss, these parameters were further significantly decreased compared to those at 30 minutes after blood loss ( P<0.05). (2) Blood cell counts: Before blood loss, the RBC count was significantly higher in the acute high-altitude THS subgroups compared to that in the plain control group ( P<0.05), while the PLT was significantly lower ( P<0.05). At 30 minutes after blood loss, there was no significant difference in RBC count between the acute high-altitude THS subgroups and the plain control group ( P>0.05), but the PLT remained significantly lower in the acute high-altitude THS subgroups ( P<0.05). At 120 minutes after blood loss, the RBC count was significantly lower in the acute high-altitude THS subgroups compared to that in the plain control group ( P<0.05), with no significant differences among the acute high-altitude THS subgroups ( P>0.05). The PLT count was significantly lower in the acute high-altitude THS+0 mg/kg TXA subgroup compared to the other subgroups ( P<0.05). The PLT count in the acute high-altitude THS+45 mg/kg TXA subgroup was significantly lower than those in the acute high-altitude THS+90 mg/kg TXA and acute high-altitude THS+135 mg/kg TXA subgroups ( P<0.05), with no significant differences between the latter two subgroups ( P>0.05). (3) Four Coagulation parameters: Before blood loss, D-dimer level was significantly higher in the acute high-altitude THS subgroups compared to that in the plain control group ( P<0.05), while no significant difference was observed in FIB ( P>0.05). APTT and PT were significantly shortened in the acute high-altitude THS subgroups ( P<0.05). At 30 minutes after blood loss, D-dimer level remained significantly higher in the acute high-altitude THS subgroups compared to that in the plain control group ( P<0.05), while FIB was significantly lower ( P<0.05), with significant increase of APTT and PT compared to those before blood loss ( P<0.05). At 120 minutes after blood loss, the acute high-altitude THS+0 mg/kg TXA subgroup exhibited significantly higher D-dimer level compared to the other subgroups ( P<0.05), with significantly lower FIB and higher APTT and PT ( P<0.05). The acute high-altitude THS+45 mg/kg TXA subgroup also showed significantly higher D-dimer level compared to those in the acute high-altitude THS+90 mg/kg TXA and acute high-altitude THS+135 mg/kg TXA subgroups ( P<0.05), with significantly lower FIB and increased APTT and PT ( P<0.05). No significant differences were observed in D-dimer, FIB, APTT or PT between the acute high-altitude THS+90 mg/kg TXA and acute high-altitude THS+135 mg/kg TXA subgroups ( P>0.05). (4) Thromboelastography parameters: Before blood loss, the R value was significantly shorter in the acute high-altitude THS subgroups compared to that in the plain control group ( P<0.05), while no significant differences were observed in K value or MA value ( P>0.05). At 30 minutes after blood loss, both R value and K value were significantly shorter in the acute high-altitude THS subgroups compared to those in the plain control group ( P<0.05), with no significant differences in MA value ( P>0.05). At 120 minutes after blood loss, the acute high-altitude THS+0 mg/kg TXA subgroup exhibited significantly increased R value and K value compared to those in the other subgroups ( P<0.05), while MA value was significantly decreased ( P<0.05). The remaining acute high-altitude THS subgroups showed significant decrease of R value and K value compared to those in the plain control group ( P<0.05), while MA value was significantly lower ( P<0.05). The acute high-altitude THS+45 mg/kg TXA subgroup exhibited significantly lower R value and K value compared to those in the acute high-altitude THS+90 mg/kg TXA and acute high-altitude THS+135 mg/kg TXA subgroups ( P<0.05), with no significant differences in R value, K value and MA value between the later two groups ( P<0.05). (5) Changes in Syndecan-1, inflammatory factors and PAI-1: Before blood loss, syndecan-1 was significantly higher in the acute high-altitude THS subgroups compared to that in the plain control group ( P<0.05), while no significant differences were observed in IL-6, TNF-α, or PAI-1 ( P>0.05). At 30 minutes after blood loss, syndecan-1, IL-6, TNF-α, and PAI-1 were significantly higher in the acute high-altitude THS subgroups compared to those in the plain control group ( P<0.05). At 120 minutes after blood loss, syndecan-1, IL-6, TNF-α, and PAI-1 were significantly higher in the acute high-altitude THS subgroups compared to those in the plain control group ( P<0.05). Among them, the acute high-altitude THS+0 mg/kg TXA group exhibited significantly higher levels of syndecan-1, IL-6, TNF-α, and PAI-1 compared to the other acute high-altitude THS subgroups ( P<0.05). The acute high-altitude THS+45 mg/kg TXA subgroup had significantly higher syndecan-1, IL-6, and TNF-α compared to those in the acute high-altitude THS+90 mg/kg TXA and acute high-altitude THS+135 mg/kg TXA subgroups ( P<0.05), with no significant difference in PAI-1 ( P>0.05). No significant differences were observed in syndecan-1, IL-6, TNF-α or PAI-1 between the acute high-altitude THS+90 mg/kg TXA and acute high-altitude THS+135 mg/kg TXA subgroups ( P>0.05). (6) Tissue injury: At 6 hours after THS, acute high-altitude THS+0 mg/kg TXA group exhibited significant interstitial thickening of the lung with extensive inflammatory cell infiltration, localized loss of intestinal brush border accompanied by cellular disruption, and marked structural disruption of renal corpuscles with focal cellular injury and necrosis. At 6 hours after THS, the acute high-altitude THS+0 mg/kg TXA subgroup exhibited significantly higher lung injury scores, Chiu′s intestinal injury scores, and kidney injury scores compared to those of the other subgroups ( P<0.05). No significant differences were observed in the tissue injury scores of the lungs, intestines and kidneys among the other subgroups ( P>0.05). The acute high-altitude THS+0 mg/kg TXA subgroup also had significantly higher lung W/D and TLW compared to those in the other subgroups ( P<0.05). At 6 hours after THS, the acute high-altitude THS+45 mg/kg TXA group exhibited significantly higher W/D and TLW of the lung tissues compared to those in the acute high-altitude THS+90 mg/kg TXA and acute high-altitude THS+135 mg/kg TXA groups ( P<0.05), with no significant differences between the latter two subgroups ( P>0.05). Conclusions:At 3 days after acute exposure to high altitude, rabbits show a hypercoagulable state of the blood, accompanied by endothelial barrier dysfunction. At 30 minutes after the induction of acute high-altitude THS, a single slow intravenous bolus injection of TXA at doses of 90 mg/kg and 135 mg/kg is more effective in improving coagulation and fibrinolysis function, inflammatory response, endothelial injury, and reduced the risk of pulmonary edema than that at a dose of 45 mg/kg.