ObjectiveTo decipher the mechanism by which Zuoguiwan （ZGW） treat hyperthyroidism in rats with kidney-Yin deficiency based on the dopamine receptor D4 （DRD4）/nicotinamide adenine dinucleotide phosphate （NADPH） oxidase 4 （NOX4） signaling pathway. MethodsThe rat model of kidney-Yin deficiency was induced by unilateral intramuscular injection of dexamethasone （0.35 mg·kg^-1）. After successful modeling， the rats were randomized into model， methimazole （positive control， 5 mg·kg^-1）， low-， medium-， and high-dose （1.85， 3.70， 7.40 g·kg^-1， respectively） ZGW， and normal control groups. After 21 days of continuous gavage， the behavioral indexes and body weight changes of rats were evaluated. The pathological changes of the renal tissue were observed by hematoxylin-eosin staining. The serum levels of thyroid hormones ［triiodothyronine （T₃）， thyroxine （T₄）， thyroid-stimulating hormone （TSH）］， renal function indexes ［serum creatine （Scr） and blood urea nitrogen （BUN）］， energy metabolism markers ［cyclic adenosine monophosphate （cAMP） and cyclic guanosine monophosphate （cGMP）］， and oxidative stress-related factors ［superoxide dismutase （SOD）， malondialdehyde （MDA）， and NADPH）］ were measured by enzyme-linked immunosorbent assay （ELISA）. Western blot was employed to analyze the expression of DRD4， NOX4， mitochondrial respiratory chain complex proteins ［NADH：ubiquinone oxidoreductase subunit S4 （NDUFS4） and cytochrome C oxidase subunit 4 （COX4）］， and inflammation-related protein ［tumor necrosis factor-alpha （TNF-α）， interleukin-6 （IL-6）， p38 mitogen-activated protein kinase （MAPK）］ pathway in the renal tissue. ResultsCompared with the normal group， the model group showed mental malaise， body weight decreases （P<0.01）， inflammatory cell infiltration in the renal tissue， a few residual parotid glands in the thyroid， elevations in serum levels of T₃， T₄， Scr， BUN， cAMP， cAMP/cGMP， MDA， and NADPH （P<0.01）， down-regulation in protein levels of TSH， SOD， and DRD4 （P<0.05， P<0.01）， and up-regulation in expression of NOX4， p-p38 MAPK/p38 MAPK， and inflammatory factors （P<0.01）. Compared with the model group， ZGW increased the body weight （P<0.05， P<0.01）， reduced the infiltration of renal interstitial inflammatory cells， restored the thyroid structure and follicle size， lowered the serum levels of T₃， T₄， Scr， BUN， cAMP， cAMP/cGMP， MDA and NADPH （P<0.05， P<0.01）， up-regulated the expression of TSH， SOD and DRD4 （P<0.05， P<0.01）， and down-regulated the expression of NOX4， p-p38 MAPK/p38 MAPK， and inflammatory factors （P<0.05， P<0.01）. Moreover， high-dose ZGW outperformed methimazole （P<0.05）. ConclusionBy activating DRD4， ZGW can inhibit the expression of NOX4 mediated by the p38 MAPK pathway， reduce oxidative stress and inflammatory response， thereby ameliorating the pathological state of hyperthyroidism due to kidney-Yin deficiency. This study provides new molecular mechanism support for the clinical application of ZGW.

Background/Aims: Liver transplantation (LT) following total hepatectomy is a life-saving treatment for hepatocellular carcinoma (HCC). The HCC recurrence after LT hinders the effectiveness of the procedure. The objective of this study is to develop a pre-operative risk stratification model based on a liquid biopsy. Methods: We conducted a comprehensive multi-omics study of 260 HCC patients from three centers, including clinical data, low-coverage whole-genome sequencing of cell-free DNA (cfDNA) from plasma, as well as whole-exome, single-nucleus RNA, and spatial transcriptomics from matched tumor and non-tumor tissues. Results: We identified cfDNA-derived copy number alteration (CNA) signatures associated with post-transplant recurrence. By integrating cfDNA-derived CNA profiles with single-cell transcriptomic data, we traced recurrence-associated cfDNA to a distinct subpopulation of malignant cells within the primary tumor. These cells were embedded in a pro-metastatic microenvironment of specialized endothelial subtypes and cancer-associated fibroblasts. Notably, most recurrence-associated lesions were detectable in cfDNA prior to liver transplantation (LT). Building on these insights, we developed the ZJU Criteria based on CNA fragments and tumor markers, a pre-LT risk prediction tool that integrates conventional clinical factors with cfDNA-derived CNA signatures, and validated it using internal and independent external cohorts. Conclusion Our findings suggest that post-transplant recurrence commonly originates from advanced subclones that emerge late during tumor evolution. The ZJU Criteria provides an accurate, non-invasive strategy that significantly improves pre-LT risk stratification and clinical decision-making for patients with HCC.

Hyperlipidemia is a common metabolic disorder driven by dysregulated lipid metabolism， whose pathological progression involves multifaceted interactions across various signaling pathways， including disrupted cholesterol homeostasis， insulin resistance， chronic inflammation， and oxidative stress. Although existing clinical medications such as statins can effectively reduce low-density lipoprotein cholesterol through single-target inhibition， significant limitations remain in comprehensively improving reverse cholesterol transport， metabolic inflammation， and coordinated regulation of glucose and lipid metabolism. Curcumin， the primary polyphenolic active compound derived from the traditional medicinal herb turmeric， exhibits multi-dimensional pharmacological effects including modulation of lipid metabolism， improvement of insulin sensitivity， suppression of inflammatory responses， and enhancement of antioxidant defense. This review systematically integrates the multi-target regulatory network of curcumin， elucidating its key mechanisms： Balancing the low density lipoprotein receptor/proprotein convertase subtilisin/kexin type 9 （LDLR/PCSK9） signaling pathway to promote reverse cholesterol transport， activating peroxisome proliferator-activated receptor α/γ （PPARα/γ） signaling pathways to coordinate glucolipid metabolic homeostasis， remodeling the gut microbiota-bile acid axis， inhibiting nuclear factor kappa-B （NF-κB）-mediated inflammatory responses， and activating the nuclear factor erythroid 2-related factor 2/antioxidant response element （Nrf2/ARE） antioxidant signaling pathway. Furthermore， supported by clinical research data， the review validates curcumin's therapeutic potential in reducing total cholesterol （TC） and triglyceride （TG） levels， increasing high-density lipoprotein cholesterol （HDL-C）， as well as improving vascular endothelial function and insulin sensitivity. The study highlights the multi-target regulatory properties of curcumin and discusses future clinical applications based on nano-delivery systems and personalized treatment strategies， providing a theoretical basis and novel insights for the prevention and treatment of hyperlipidemia and related metabolic disorders.

AIM To investigate the promotional effects of esculin combined with bone marrow mesenchymal stem cells(BM-MSCs)transplantation on the repair of spinal cord injury(SCI)in rats.METHODS The rats were randomly divided into the sham operation group,the model group,the esculin group for gavage of 20 mg/kg esculin,the BM-MSCs group for tail vein injection of 1 mL of 1×106/mL BM-MSCs,and the combinaiton treatment group.The SCI rat model was established using Allen's method,followed by the 14 days consecutive corresponding drug administration starting from the 2nd day after modeling.On days 3,7 and 14 of drug administration,the rats had their hind limbs motor function evaluated by the BBB scoring;and their footprint experiment conducted on the 14th day after modeling.After 14 days of administration,the rats had their morphological changes of spinal cord tissue observed with HE staining and Nissl staining;their activities of SOD and GSH,and level of MDA in spinal cord tissue detected by kits;their expressions of MAP2,GAP43 and GFAP in spinal cord tissue detected by immunofluorescence;and their expressions of NQO-1,Nrf-2,Bcl-2 and Bax proteins in spinal cord tissue detected by Western blot.RESULTS Compared with the model group,the groups interved with esculin,or BM-MSCs,or the combination treatment showed improvements in hind limb function and spinal cord tissue morphology(P＜0.05);decreased MDA levels(P＜0.05);increased SOD and GSH activities(P＜0.05);increased MAP2 and GAP43 fluorescence intensity(P＜0.05);decreased GFAP fluorescence intensity(P＜0.05);increased NQO-1,Nrf-2 and Bcl-2 protein expressions(P＜0.05);and decreased Bax protein expression(P＜0.05).And the combination treatment group was observed with an even better effects(P＜0.05).CONCLUSION The combination of esculin and BM-MSCs transplantation can effectively improve the spinal cord tissue damage and hind limb function in SCI rats.This effect may be achieved by activating the Nrf-2/NQO-1 signaling pathway to inhibit oxidative stress response,thereby reducing neuronal apoptosis,blocking glial scar formation,and promoting stem cell differentiation to rebuild neurons.

Objective:To investigate the relationship between serum apolipoprotein A1 (ApoA1), cytotoxic T lymphocyte-associated antigen-4 (CTLA-4), proinflammatory protein S100A9 (S100A9) and prognosis in patients with myelodysplastic syndrome (MDS).Methods:122 MDS patients visited Qinhuangdao First Hospital from January 2020 to January 2021 were selected as the research objects. After three years of follow up, patients were divided into survival group and death group based on survival status. The differences in ApoA1, CTLA-4, and S100A9 between the death group and the survival group were compared. Measurement data with normal distribution was expressed as " xˉ±s", independent sample t-test was used on comparison between groups. Counting data was expressed as rate or composition ratio, χ2 test was used on comparison between groups. Univariate and multivariate Logistic regression analysis were used to analyze factors related to death. Results:There was no lost to follow up patients after three years of follow up. Among those 122 patients, 92 survived and 30 died. The ratio of bone marrow primitive cells>5%, IPSS-R score, serum CTLA-4, and S100A9 levels in the survival group were (2.89±2.15), (3.13±1.95) points, (5.12±1.59) μg/L, (1643.98±429.65)ng/L, respectively, lower than (5.67±3.76), (5.12±2.36) points, (28.67±6.98) μg/L, (2895.64±553.62) ng/L in the death group ( t=5.03, 4.60, 30.27, 12.87, respectively, all P<0.01). The relative high-risk ratio of IPSS-R stratification in the survival group was 63.04%,(58/92) which was lower than the 86.67%(26/30) in the death group ( χ2=5.89, P=0.015). The absolute values of hemoglobin, lymphocytes and neutrophils, and values of platelets and ApoA1 in the survival group were(86.74±12.69)g/L, (1.41±0.23)×10 9/L, (1.42±0.55)×10 9/L, (59.98±21.37)×10 9/L, (1.09±0.40) g/L respectively, which were higher than (65.58±10.89)g/L, (0.68±0.17)×10 9/L, (0.96±0.31)×10 9/L, (42.85±20.95)×10 9/L, (0.91±0.36)g/L in the death group ( t=8.20, 16.00, 4.35, 7.90, 2.19; respectively, P<0.001, <0.001, <0.001, <0.001, =0.030). Multivariate Logistic regression model analysis showed that, bone marrow blasts cells>5% ( OR=1.732, 95% CI: 1.188~2.523, P=0.004), relatively high IPSS-R stratification ( OR=1.815, 95% CI: 1.332~2.474, P<0.001), high IPSS-R score ( OR=1.785, 95% CI: 1.259~2.529, P=0.001), high CTLA-4 level ( OR=2.156, 95% CI: 1.482~3.134, P<0.001) and high S100A9 level ( OR=1.787, 95% CI: 1.218~2.625, P=0.003) were risk factors for poor prognosis in MDS patients, while high ApoA1 level ( OR=0.785, 95% CI: 0.658~0.937, P=0.007) was a protective factor ( P<0.05). Conclusion:The decrease in ApoA1 levels and the increase in CTLA-4 and S100A9 levels in MDS patients are associated with poor prognosis.

Objective To compare the application effects of plankton multiplex polymerase chain reac-tion-capillary electrophoresis(PCR-CE),SYBR Green Ⅰ real-time quantitative PCR(qPCR)and microwave digestion-vacuum filtration-automated scanning electron microscopy(MD-VF-Auto SEM)in the diagnosis of drowning.Methods Lung,liver and kidney tissues from 212 drowned corpses and 30 non-drowned corpses were examined respectively by the three drowning-related plankton testing methods,and the detection rates of plankton in each tissue by three methods were compared.Results In drowned corpses,the total detection rates of PCR-CE,qPCR,and MD-VF-Auto SEM were 93.9%,96.2%,and 95.3%,respectively,with no statistically significant difference(P>0.05).The detection rate of lung tissue by MD-VF-Auto SEM(100%)was higher than those of PCR-CE and qPCR(P<0.05),and there was no significant difference in the detection rates of the three methods in liver or kidney tissues(P>0.05).In non-drowning corpses,a small number of diatoms(less than 10 cells/10 g)were detected by MD-VF-Auto SEM method,only in liver and kidney tissues,while the other two methods yielded negative results for all tissues.Conclusion All three methods have good efficacy in the examination of drowned corpses.The MD-VF-Auto SEM method directly observes diatom morpho-logical characteristics through scanning electron microscopy,and the qualitative and quantitative analy-ses are intuitive and accurate.It has great advantages in the examination of difficult degradation samples.The PCR-CE method and qPCR method have a low sample demand(0.5 g),are easy to operate and have short detection time(4-7 h).They are easy to be applied in the grassroots depart-ments and are suitable for the rapid determination of drowned corpses in routin cases.The combina-tion of the two DNA methods with the MD-VF-Auto SEM method can increase the detection rate of plankton,ensuring the reliability of examination results.This combined use is of significant importance in the application of drowning diagnosis.

Objective: To retrospectively compare the safety and efficacy of ultrasound-guided radiofrequency ablation (RFA) with parotidectomy for superficial pleomorphic adenoma (PA). Materials and Methods: From March 2022 to October 2023, 88 patients diagnosed with superficial parotid PA underwent either RFA (n = 12; mean age, 47.1 years) or parotidectomy (n = 76; mean age, 47.8 years). Patients in the RFA group were matched to those in the surgery group in a 1:1 ratio using propensity scores based on age, sex, tumor volume, diameter, location, and comorbidities. Ultrasound characteristics, cosmetic scores (0–4), numerical rating scale scores (0–10), and complications were assessed before the procedures and at 1-, 3-, and 6-month follow-ups. Outcomes were compared between baseline and follow-up in the RFA group and between the RFA and surgery groups. Results: In the RFA group, significant reductions in tumor volume were observed between baseline (median, 2.02 cm 3 ) and the 1-month follow-up (median, 1.21 cm 3 ; P = 0.015), between the 1-month and 3-month follow-ups (median, 0.53 cm 3 ; P= 0.002), and between the 3- and 6-month follow-ups (median, 0.23 cm 3 ; P = 0.003). The volume reduction ratios at 1, 3, and 6 months were 39.7%, 79.9%, and 88.0%, respectively. The cosmetic score was significantly lower at 3- and 6-month followup compared to baseline (median 1 and 1 vs. 4, P = 0.04). The numerical rating scale scores did not differ significantly from baseline throughout follow-up. In the propensity score-matched analysis (12 patients per group), RFA was associated with a shorter median procedure time (61.5 vs. 253.3 minutes; P < 0.001), shorter hospital stay (0 vs. 4 days; P < 0.001), and lower cost (1859.9 vs. 3512.4 USD; P < 0.001) than parotidectomy, with no significant difference in overall complication rates (33.3% [4/12] vs. 41.7% [5/12]; P = 1.000). Conclusion RFA may be a safe and effective alternative to surgery for superficial parotid PA, offering a shorter median procedure time, shorter hospital stay, and lower costs.

BACKGROUND: The use of inserted sham acupuncture as a placebo in randomized controlled trials (RCTs) is controversial, because it may produce specific effects that cause an underestimation of the effect of acupuncture treatment. OBJECTIVE: This systematic survey investigates the magnitude of insert-specific effects of sham acupuncture and whether they affect the estimation of acupuncture treatment effects. SEARCH STRATEGY: PubMed, Embase and Cochrane Central Register of Controlled Trials were searched to identify acupuncture RCTs from their inception until December 2022. INCLUSION CRITERIA: RCTs that evaluated the effects of acupuncture compared to sham acupuncture and no treatment. DATA EXTRACTION AND ANALYSIS: The total effect measured for an acupuncture treatment group in RCTs were divided into three components, including the natural history and/or regression to the mean effect (controlled for no-treatment group), the placebo effect, and the specific effect of acupuncture. The first two constituted the contextual effect of acupuncture, which is mimicked by a sham acupuncture treatment group. The proportion of acupuncture total effect size was considered to be 1. The proportion of natural history and/or regression to the mean effect (PNE) and proportional contextual effect (PCE) of included RCTs were pooled using meta-analyses with a random-effect model. The proportion of acupuncture placebo effect was the difference between PCE and PNE in RCTs with non-inserted sham acupuncture. The proportion of insert-specific effect of sham acupuncture (PIES) was obtained by subtracting the proportion of acupuncture placebo effect and PNE from PCE in RCTs with inserted sham acupuncture. The impact of PIES on the estimation of acupuncture's treatment effect was evaluated by quantifying the percentage of RCTs that the effect of outcome changed from no statistical difference to statistical difference after removing PIES in the included studies, and the impact of PIES was externally validated in other acupuncture RCTs with an inserted sham acupuncture group that were not used to calculate PIES. RESULTS: This analysis included 32 studies with 5492 patients. The overall PNE was 0.335 (95% confidence interval [CI], 0.255-0.415) and the PCE of acupuncture was 0.639 (95% CI, 0.567-0.710) of acupuncture's total effect. The proportional contribution of the placebo effect to acupuncture's total effect was 0.191, and the PIES was 0.189. When we modeled the exclusion of the insert-specific effect of sham acupuncture, the acupuncture treatment effect changed from no difference to a significant difference in 45.45% of the included RCTs, and in 40.91% of the external validated RCTs. CONCLUSION The insert-specific effect of sham acupuncture in RCTs represents 18.90% of acupuncture's total effect and significantly affects the evaluation of the acupuncture treatment effect. More than 40% of RCTs that used inserted sham acupuncture would draw different conclusions if the PIES had been controlled for. Considering the impact of the insert-specific effect of sham acupuncture, caution should be taken when using inserted sham acupuncture placebos in RCTs. Please cite this article as: Luo XC, Liu JL, Yao MH, Chen YM, Fan AY, Liang FR, Zhao JP, Zhao L, Zhou X, Zhong XY, Yang JH, Li B, Zhang Y, Sun X, Li L. Specific effect of inserted sham acupuncture and its impact on the estimation of acupuncture treatment effect in randomized controlled trials: A systematic survey. J Integr Med. 2025; 23(6):630-640.
Acupuncture Therapy/methods* ; Humans ; Randomized Controlled Trials as Topic ; Placebo Effect ; Placebos ; Treatment Outcome

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.