Background: and Purpose In patients with large vessel occlusion (LVO), intravenous thrombolysis (IVT) frequently alters thrombus location; however, the clinical impact of this phenomenon remains unclear. We aimed to compare post-IVT thrombus dynamics between tenecteplase and alteplase and to evaluate the association between thrombus dynamics and 3-month outcomes. Methods: This retrospective study analyzed prospectively collected, multicenter data from consecutive patients with LVO who underwent bridging therapy between January 2022 and December 2024. Thrombus dynamics were classified as resolution, migration, or stability. Analyses incorporated propensity score matching with weighting to balance baseline characteristics. Results: Of the 806 initially included patients, 746 were included after matching (373 treated with tenecteplase and 373 treated with alteplase). The incidence of thrombus migration was significantly higher in the tenecteplase group than in the alteplase group (19.3% vs. 11.3%; odds ratio [OR]: 1.92; 95% confidence interval [CI] 1.27–2.91). The advantage of tenecteplase over alteplase was restricted to patients with an IVT-to-puncture time of <60 minutes (18.6% vs. 6.2%; p=0.001) and was no longer significant when the interval ≥60 minutes (19.7% vs. 15.0%; p=0.204; pinteraction=0.043). Additionally, thrombus migration was associated with a better functional outcome (OR: 1.62; 95% CI 1.04–2.53). Finally, tenecteplase was associated with improved functional independence compared with alteplase (OR: 1.43; 95% CI 1.04–1.95). Conclusions Tenecteplase demonstrated superior efficacy in inducing thrombus migration compared with alteplase, particularly within 60 minutes of IVT administration. Thrombus migration independently predicted improved functional independence. These findings support the preferential use of tenecteplase for bridging therapy in patients with LVO.

To investigate whether Tasquinimod can influence cisplatin resistance in drug-resistant ovarian cancer (OC) cell lines by regulating histone deacetylase 4 (HDAC4) or p21, we explored its effects on the cell cycle, and associated mechanisms.RT-PCR and Western blot analyses, flow cytometry, CCK8 assay, and immunofluorescence were utilized to investigate the effects of Tasquinimod on gene expression, cell cycle, apoptosis, viability, and protein levels in OC cells. The results showed that Tasquinimod inhibited cell viability and promoted apoptosis in SKOV3/DDP (cisplatin) and A2780/DDP cells more effectively than DDP alone. In combination with cisplatin, Tasquinimod further enhanced cell apoptosis and reduced cell viability in these cell lines, an effect that could be reversed following HDAC4 overexpression. Tasquinimod treatment down-regulated HDAC4, Bcl-2, and cyclin D1, and CDK4 expression and up-regulated the cleaved-Caspase-3, and p21 expression in SKOV3/DDP and A2780/ DDP cells. Additionally, Tasquinimod inhibited DDP resistance in OC/DDP cells. These effects were similarly observed in OC mouse models treated with Tasquinimod. In conclusion, Tasquinimod can improve OC cells' sensitivity to DDP by down-regulating the HDAC4/p21 axis, offering insights into potential strategies for overcoming cisplatin resistance in OC.

Aim To investigate the effect of dihydro-myricetin(DMY)on Ang Ⅱ-induced cardiac hypertro-phy in mice and the underlying mechanisms.Methods Fifty mice were randomly divided into control group,Ang Ⅱ group,Ang Ⅱ+catopril 12.0 mg·kg-1·d-1 group,AngⅡ+DMY 100 mg·kg-1·d-1 group,and Ang Ⅱ+DMY 200 mg·kg-1·d-1 group,with 10 mice in each group.The control mice were given saline by gavage,the drug intervention group was given DMY,and the positive drug group was given captopril;the mice in all groups except the control group were in-jected subcutaneously with Ang Ⅱ 1.0mg·kg-1·d-1.After four weeks,heart weight/body weight(HW/BW)and left ventricular weight/body weight(LVW/BW)ratios were calculated.The mRNA ex-pression of the fetal genes atrial natriuretic factor(ANF),brain natriuretic peptide(BNP),β-myosin heavy chain(β-MHC),adenosine triphosphate 5β-subunit(ATP 5β)and uncoupling protein 2(UCP2)were monitored,and the morphological changes of car-diac tissue were observed.Secondly,the creatine ki-nase isoenzyme(CK-MB),lactate dehydrogenase(LDH),free fatty acids(FFA)and lactic acid in ser-um were investigated.Lastly,the expression of AMP-activated proteinkinase(AMPK),peroxisome prolifer-ator-activated receptor alpha(PPAR-α)and T-cell nu-clear factor cytoplasmic 4(NFATc4)protein expres-sion were also detected.The Ang Ⅱ-induced H9C2 cardiomyocyte hypertrophy model was established and treated with the AMPK inhibitor compound C.The mRNA of ANF,BNP,β-MHC and the protein expres-sion of AMPK/PPAR-α were analyzed.Results DMY intervention significantly reduced HW/BW and LVW/BW in mice,fetal genes ANF,BNP,β-MHC and UCP2 mRNA expression decreased,whereas ATP 5 β mRNA increased,and the degree of hypertrophy of cardiomyocytes was alleviated.In addition,the serum levels of CK-MB,LDH,FFA and lactic acid were re-duced in DMY treated groups.Finally,DMY upregu-lated the protein expression of P-AMPK,AMPK and PPAR-α,and downregulated protein expression of NFATc4.In the Ang Ⅱ-induced cardiomyocyte hyper-trophy model,DMY pretreatment reduced the mRNA expression of fetal genes(ANF,BNP,β-MHC).However,when AMPK was inhibited by compound C,the expression of these fetal genes rebounded,accom-panied by decreased protein levels of AMPK and PPAR-α.Conclusions DMY can improve Ang Ⅱ-in-duced myocardial hypertrophy in mice by ameliorating disorders of glycolipid metabolism and increasing ener-gy supply to cardiomyocytes,and its mechanism is re-lated to the activation of the AMPK/PPAR-α pathway and the inhibition of NFATc4 expression.

[Purpose]To analyze the compliance and its influencing factors of lung cancer screening using low-dose computed tomography(LDCT)among high-risk population in urban districts of Chongqing from 2013 to 2021.[Methods]The lung cancer screeing of Cancer Early Diagnosis and Treatment Project was conducted among permanent residents aged 40～69 years old from 14 urban districts of Chongqing selected by cluster sampling method from 2013 to 2021.The questionnaire survey was performed to assess the risk level of lung cancer,and individuals with high risk were advised to have LDCT examination.The compliance rate of LDCT examination among high-risk populations was calculated and compared using Chi-square test among residents with different de-mographic features;the influencing factors of compliance was analyzed with generalized linear mixed models.[Results]A total of 316 066 residents completed the risk assessment questionnaire survey,52 858 people were assessed as high-risk(17.17％).Among the high-risk population,20 398 completed LDCT screening,with an overall compliance rate of 38.59％.The generalized linear mixed model showed that male participants(OR=0.871,95％CI:0.823～0.922)and smokers(light smokers:OR=0.829,95％CI:0.775～0.886;heavy smokers:OR=0.842,95％CI:0.792～0.896)had lower compliance rates;while people with higher education level(OR=1.347,95％CI:1.265～1.435),occupational exposure to harmful substances(OR=1.400,95％CI:1.340～1.463),passive smoking for 20 years or more(OR=1.472,95％CI:1.376～1.576),infrequent physical exercise(OR=1.203,95％CI:1.152～1.256),family history of lung cancer(OR=2.312,95％CI:2.201～2.429),and those having media promotion by community staff(OR=1.365,95％CI:1.223～1.524),and trained community staff(OR=1.343,95％CI:1.227～1.470)had higher compliance rates.Comorbidities were also factors influencing compliance,and there was an increasing trend of compliance rate with the increase of comorbidity numbers(P＜0.001).[Conclusion]The compli-ance rate of LDCT examination for lung cancer screening in Chongqing needs to be improved,and more precise health education should be implemented for groups with different characteristics to improve the compliance among high-risk population.

Aim To study the role and mechanism of ML210 in glioma.Methods The cell viability was detected by CCK8 assay.The percentage of dead cells was detected by SYTOXstaining.The role of ferroptosis-signaling pathway in gliomas was detected bygenomics.Cell proliferation was observed by EdU staining and clone formation assay.Cell migration ability was detec-ted by scratch healing assay.The apoptosis was detec-ted by flow cytometry.Cell mitochondrial function was assesses by JC-1 staining.The mechanism of action of ML210 was detected by molecular docking coupled with immunoblotting assay(Western blot).The levels of ROS,MDA were observed by ELISA.Results Compared with the control group,ML210 treatment dose-dependently decreased glioma cell viability,in-hibited cell proliferation,migration,and increased cell apoptosis and mitochondrial dysfunction,which were reversed by ferroptosis antagonists.Gene microarray screening showed that 688 genes of the ferroptosissig-naling pathway were aberrant and 10 signaling path-ways were altered in gliomas.Molecular docking re-sults showed that ML210 binding to GPX4 significantly inhibited the protein expression level of GPX4 and pro-moted the elevation of ROS and MDA levels.Conclu-sions ML210 produces anti-glioma cells via GPX4-mediated ferroptosis pathway.

Objective To evaluate the efficacy and safety of Qixian Tongluo Formula in the treatment of post-cerebral infarction paralysis with kidney deficiency and blood stasis syndrome,and to preliminarily explore the molecular mechanism of Qixian Tongluo Formula in improving impaired motor function from the perspective of cross-kingdom regulation of Chinese medicine microRNA(miRNA).Methods A pragmatic randomized controlled trial was conducted with 102 patients in the recovery period of post-cerebral infarction paralysis with kidney deficiency and blood stasis syndrome in our hospital.Patients were randomly divided into trial group and control group,with 51 cases in each group.The control group received standard Western medicine standard treatment,while the trial group received Qixian Tongluo Formula in addition to the standard treatment,with one dose per day,boiled in water,and taken warm after breakfast and dinner for a course of 2 months.The disability rate was used as the main efficacy indicator,and the incidence of adverse reactions was used as a safety indicator.miRNA from patient serum and Qixian Tongluo decoction were extracted respectively,and high-throughput sequencing was performed.The two sequences were compared to screen out the cross-kingdom gene transfer of Chinese medicine miRNA.Finally,its target genes of miRNA were predicted,and GO function and KEGG pathway enrichment analysis were carried out.Results A total of 67 patients completed the clinical trial,including 36 cases in the trial group and 31 cases in the control group;The disability rate in the trial group(13.9%)was lower than that in the control group(35.5%)(P<0.05);The incidence of adverse reactions was similar between the trial group(7.69%)and the control group(6.06%)(P>0.05);A total of 9530 Qixian Tongluo decoction miRNA sequences were screened,with 150 potentially involved in cross-kingdom gene transfer,including families such as miR-15 and miR-17;According to the target gene prediction of the top 10 miRNAs in cross-kingdom gene transfer of Chinese medicine,345 overlapping target genes were obtained;GO functional enrichment analysis revealed 16 biological processes,7 cellular components,and 2 molecular functions among the top 25 enriched functions,while KEGG pathway analysis mainly focused on the transforming growth factor-βsignaling pathway,neurotrophin signaling pathway,which are closely related to neural repair and functional recovery processes such as glial scar formation and synaptic plasticity after cerebral ischemia.Conclusion Qixian Tongluo Formula can significantly improve the functional independence level of patients with kidney deficiency and blood stasis syndrome in the recovery period of paralysis after cerebral infarction,offering a safe and effective treatment option for these patients;There were a large number of miRNAs in Qixian Tongluo decoction,some of which could cross-kingdom transferred into the human blood circulation,and promote the recovery of motor function in patients with cerebral infarction through multi-target,multi link and multi pathway gene network regulation.This study provides a new idea for subsequent clinical and basic research.

Aim To explore the mechanism of Jiawei Shaofu Zhuyu decoction in antagonizing endometriosis fibrosis by regulating mitophagy.Methods After the animal model was constructed,the syndrome was evalu-ated by general condition,organ water content and ther-mal imaging.The curative effect was evaluated by the weight of ectopic focus and the degree of adhesion.The pathological changes were compared using HE stai-ning,transmission electron microscopy,Masson and Sir-ius red staining.The expression of PINK1 and Parkin was detected by immunohistochemistry.The expression of mRNA and protein was determined by qPCR and Western blot,and the level of serum ROS was detected by ELISA.Results The autonomic activity of model mice was weakened,the water content of organs rose,and the temperature of limbs and lower abdomen was reduced by thermal imaging.HE staining showed obvi-ous hyperplasia of ectopic epithelium and glands.Transmission electron microscopy showed mitochondrial and endoplasmic reticulum structure damage,and nor-mal autophagy structure disappeared.Masson and Siri-us red staining showed increased collagen deposition;immunohistochemistry showed decreased expression of PINK1 and Parkin in ectopic foci.qPCR and Western blot showed that the expression of PINK1,Parkin,Bec-lin1,LC3 mRNA and protein in ectopic foci of model mice decreased,the expression of p62 mRNA and pro-tein increased,and serum ROS increased.The syn-drome performance of model mice was improved after the intervention of Jiawei Shaofu Zhuyu decoction;the inflammatory infiltration of ectopic foci was relieved,the morphology of mitochondria and endoplasmic retic-ulum was restored,and normal autophagy structure ap-peared.The degree of collagen deposition and fibrosis was reduced;the mRNA and protein expression of PINK1,Parkin,Beclin1 and LC3 increased.The ex-pression of p62 mRNA and protein decreased,and the level of ROS decreased.Conclusions Jiawei Shaofu Zhuyu decoction can improve the fibrosis of ectopic le-sions in mice with endometriosis of cold-dampness sta-sis syndrome,which may be related to the regulation of mitophagy.

BACKGROUND:According to different locations of lumbar disc herniation,it can be classified into many types.Among them,patients with intradural sac type lumbar disc herniation have severe clinical symptoms,which greatly affect their quality of life.Therefore,this article studies the risk factors for its onset,and improving the preoperative diagnostic rate is of great significance for the treatment and prevention of this disease.OBJECTIVE:To explore the risk factors for intradural lumbar disc herniation.METHODS:A retrospective analysis was conducted on 15 patients with intradural lumbar disc herniation(herniation group)admitted to three hospitals in Xuzhou city from May 2014 to November 2022.Propensity score matching was used to match patients with lumbar disc herniation who did not protrude into the dura mater in a ratio of 1:4.A total of 59 patients were selected and included in the non-herniation group.Clinical data were observed in the two groups.Univariate and binary logistic regression analysis,multiple linear regression,and PROBIT regression analysis were utilized to identify the relevant risk factors for intradural lumbar disc herniation.RESULTS AND CONCLUSION:(1)The results of univariate analysis showed that the average disease course,proportion of segments,modified Pfiirmann grading,sacral tilt angle,proportion of previous lumbar spine surgery history,and proportion of heavy manual workers,proportion of lumbar spinal stenosis,redundancy of the cauda equina,and ossification of the posterior longitudinal ligament all showed statistical differences in the herniation and non-herniation groups(P＜0.05).(2)Multivariate regression analysis showed that duration of disease,protruding segment,history of lumbar surgery,modified Pfiirmann grading,cauda equina redundancy,and lumbar spinal stenosis were independent risk factors for intradural lumbar disc herniation.(3)Based on the influencing factors,an receiver operating characteristic curve was constructed,with an area under curve of 0.956(95％CI:0.913-0.998),indicating good discrimination.(4)There was a significant correlation between the duration of the disease,the protruded segment,the history of lumbar spine surgery,the modified Pfirmann classification,cauda equina redundancy,lumbar spinal canal stenosis,and the incidence rate of intradural lumbar disc herniation.

Advances in genomics,biochemistry,and genetics have deepened our understanding of epigenetic mechanisms.These mechanisms play a crucial role in life,heredity,and evo-lution.Their growing significance is driving biomedical research toward personalized and precise medicine.Renal diseases,par-ticularly chronic kidney disease and acute kidney injury,require new treatment strategies.Their subtle clinical symptoms and challenges in early diagnosis limit current therapeutic options.Research on epigenetic modifications in renal diseases is expan-ding rapidly.This field is emerging as a promising approach for kidney disease treatment.The transition from basic mechanistic studies to clinical applications is underway.Epigenetic modifica-tions hold great potential for improving early diagnosis,enabling personalized treatment,and advancing precision medicine in re-nal diseases.

Aim To investigate the effects of rutae-carpine(RUT)on lung inflammation in septic mice and the underlying mechanisms.Methods The sepsis mouse model was generated by intraperitoneal injection of lipopolysaccharide(LPS)at 5 mg·kg-1.The mice were randomly divided into the Control group,Model group,Low-dose,Medium-dose,High-dose RUT(5,10,20 mg·kg-1)treatment group and dexamethasone(DEX,2 mg·kg-1),with 10 mice in each group.The mice were intraperitoneally injected with RUT 30 min before LPS injection.HE staining was used to observe the morphology of lung tissues,and activity of my-eloperoxidase was determined to assess the neutrophil infiltration.Wet/dry weight ratio and Evan's blue ex-travasation of lung tissues were examined to assess lung edema.Survival analysis was performed to determine the in vivo protective effects of RUT.ELISA and quan-titative RT-PCR analysis were employed to determine the contents and gene expression of pro-inflammatory mediators,including tumor necrosis factor-α(TNF-α),interleukin-1 β(IL-1 β),IL-6,and IL-18 in lung tis-sues.Western blot was used to detect the protein levels of p38 MAPK,NF-κB,Caspase-1,NOD-like receptor family pyrin domain containing 3(NLRP3)and IL-18.Results RUT at 10-20 mg·kg-1 could dose-de-pendently inhibit leukocyte infiltration,reduce pro-in-flammatory mediator production,vascular permeability and wet/dry weight ratio in lungs,similar to the effects induced by DEX.The mice treated with RUT exhibited increased survival,down-regulated expressions of p-p38 MAPK,p-NF-κB,Caspase-1,NLRP3,and IL-18 pro-teins in lungs,with decreased IL-18 mRNA level.Conclusions RUT exhibits protective effects on sep-sis-induced lung injury,manifested by reduced inflam-mation and edema,potentially via inhibition of p38 MAPK signaling pathway and inflammasome formation.