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.

Objective To investigate the effect of irisin regulating early B cytokine 3(EBF3)/arachidonic acid-15-lipoxygenase(ALOX15)pathway on the proliferation and migration of lung adenocarcinoma cells.Methods A549 cells were assigned into the irisin solvent group,the irisin group,the sh-NC group,the EBF3 inhibitor(sh-EBF3)group,the irisin+sh-NC group and the irisin+sh-EBF3 group randomly.5-bromo-2-deoxyuracil(EdU)staining and CCK-8 method were applied to detect cell proliferation.5-Scratch experiment was applied to detect the scratch healing rate.2',7'-dichlorofluorescein diacetate(DCFH-DA)staining was applied to detect the level of reactive oxygen species(ROS)in cells.The reagent kit was used to detect glutathione(GSH),malondialdehyde(MDA)and ferrous ion(Fe2+)in cells.Transmission electron microscopy was applied to observe mitochondrial morphology in A549 cells.QRT-PCR was applied to detect mRNA levels of proliferating cell nuclear antigen(PCNA),matrix metalloproteinase 2(MMP-2)and glutathione peroxidase 4(GPX4)in A549 cells.Western blot assay was applied to detect EBF3 and ALOX15 proteins in cells.Results Compared with the irisin solvent group,the mitochondria of A549 cells in the irisin group showed ferroptosis characteristics,the positive rate of EdU,OD450 value,scratch healing rate,GSH level,PCNA,MMP-2 and GPX4 mRNA levels decreased,and the ROS relative fluorescence intensity,MDA,Fe2+level,and EBF3 and ALOX15 protein levels increased(P＜0.05).Compared with the sh-NC group,the mitochondrial ferroptosis phenomenon of A549 cells was reduced in the sh-EBF3 group,the positive rate of EdU,OD450 value,scratch healing rate,GSH level,PCNA,MMP-2 and GPX4 mRNA levels increased,and the ROS relative fluorescence intensity,MDA,Fe2+levels and EBF3 and ALOX15 protein levels reduced(P＜0.05).Sh-EBF3 reversed the effect of irisin on ferroptosis,proliferation and migration of A549 cells.Conclusion Irisin may induce ferroptosis in A549 cells and inhibit cell proliferation and migration by activating the EBF3/ALOX15 pathway.

Objective To investigate the effect of irisin regulating early B cytokine 3(EBF3)/arachidonic acid-15-lipoxygenase(ALOX15)pathway on the proliferation and migration of lung adenocarcinoma cells.Methods A549 cells were assigned into the irisin solvent group,the irisin group,the sh-NC group,the EBF3 inhibitor(sh-EBF3)group,the irisin+sh-NC group and the irisin+sh-EBF3 group randomly.5-bromo-2-deoxyuracil(EdU)staining and CCK-8 method were applied to detect cell proliferation.5-Scratch experiment was applied to detect the scratch healing rate.2',7'-dichlorofluorescein diacetate(DCFH-DA)staining was applied to detect the level of reactive oxygen species(ROS)in cells.The reagent kit was used to detect glutathione(GSH),malondialdehyde(MDA)and ferrous ion(Fe2+)in cells.Transmission electron microscopy was applied to observe mitochondrial morphology in A549 cells.QRT-PCR was applied to detect mRNA levels of proliferating cell nuclear antigen(PCNA),matrix metalloproteinase 2(MMP-2)and glutathione peroxidase 4(GPX4)in A549 cells.Western blot assay was applied to detect EBF3 and ALOX15 proteins in cells.Results Compared with the irisin solvent group,the mitochondria of A549 cells in the irisin group showed ferroptosis characteristics,the positive rate of EdU,OD450 value,scratch healing rate,GSH level,PCNA,MMP-2 and GPX4 mRNA levels decreased,and the ROS relative fluorescence intensity,MDA,Fe2+level,and EBF3 and ALOX15 protein levels increased(P＜0.05).Compared with the sh-NC group,the mitochondrial ferroptosis phenomenon of A549 cells was reduced in the sh-EBF3 group,the positive rate of EdU,OD450 value,scratch healing rate,GSH level,PCNA,MMP-2 and GPX4 mRNA levels increased,and the ROS relative fluorescence intensity,MDA,Fe2+levels and EBF3 and ALOX15 protein levels reduced(P＜0.05).Sh-EBF3 reversed the effect of irisin on ferroptosis,proliferation and migration of A549 cells.Conclusion Irisin may induce ferroptosis in A549 cells and inhibit cell proliferation and migration by activating the EBF3/ALOX15 pathway.

Thousands of variant gene sequences of SARS-CoV-2 have been emerged since the COVID-19 epidemic broke out in Dec.2019.Alpha(B.1.1.7),Beta(B.1.351),Gamma(P.1),Delta(B.1.617.2)and Omicron(B.1.1.529)were the most representative variants.With the continuous emergence of new variants,the predomi-nant strain in the global pandemic as of Jan.2025 is the Omicron BA.2.86-derived mutant,JN.1.The effectiveness of drugs against Omicron variants remains a key research focus in the treatment of SARS-CoV-2 infections.The infectiousness and pathogenicity of the variants altered remarkably due to mutations in the genome on S protein of the mutant strains,and these emerging variants are more likely to evade immunity and were more infectious than the previous prevalent variants.During the process of combating with the constantly emerging novel variants,drugs showed various effects on treatment of diseases caused by different variants.New drugs and treatment coun-termeasures are constantly updated with the prevalence of various variants.The current status of research on pres-ent drugs for treatment of SARS-CoV-2 and the therapeutic effects on emerging variants are reviewed in the article so as to provide reference for prevention and treatment of the upcoming evolved variants.

Objective To develop and validate a nomogram model for predicting recurrence after radiofre-quency catheter ablation(RFCA)in patients with atrial fibrillation and heart failure using body surface electrocar-diogram indicators and clinical indicators.Methods We retrospectively analyzed 305 patients with atrial fibrilla-tion complicated with heart failure who underwent RFCA from January 2019 to January 2024.Patients were random-ized into training set(213 cases)and validation set(92 cases)at a ratio of 7:3 and followed up for at least 1 year.Based on the recurrence status,the patients were divided into recurrence group and non-recurrence group,with body surface electrocardiogram indicators and clinical indicators collected.Multivariate logistic regression analysis identified for risk factors for post RFCA recurrence,which were used to construct a nomogram.Model performance was assessed using the area under the receiver operating characteristic curve(AUC),Hosmer-Lemeshow test,calibration curves,and decision curve analysis(DCA).Results Among the 305 patients,84(27.54％)experi-enced recurrence after treatment.In the training set,61 patients had recurrence and 152 did not.No statistical differences were observed between the training set and the validation set(all P>0.05).In the training set,the recurrence group exhibited a higher proportion of persistent atrial fibrillation and significantly higher CHA2DS2-VASc scores,larger left atrial diameter,longer PR interval,and higher levels of NLR and NT-proBNP compared to the non-recurrence group(all P<0.05).Multivariate stepwise regression analysis revealed that high CHA2DS2-VASc score,long left atrial diameter,prolonged PR interval,and high NLR were independent risk factors of recurrence after RFCA(P<0.05)A four-factor prediction model was established as:Ln(P/1-P)=-12.87+0.84*CHA2DS2-VASc score+0.11* left atrial diameter+0.03*PR interval+0.31*NLR.The training and validation models showed AUCs of 0.85(95％CI:0.80～0.91)and 0.85(95％CI:0.76～0.94),respectively,suggesting that the model had good predictive efficiency.Hosmer-Lemeshow test results(χ2=2.43,P=0.965 for the training set;χ2=5.30,P=0.725 for the validation set)confirmed model fit,indicating that the fitted probability value was consistent with the actual probability value.Calibration curves after 1 000 times of Bootstrap repeated sampling showed the bias calibration curves of the training set and the validation set had good consistency with the actual curves,both close to the ideal curve.DCA revealed clinical utility across a wide threshold probability range(0.02～1.0 for the training set;0.04～1.0 for the validation set).Conclusion This nomogram,based on body surface electrocardiogram indicators and clinical indicators,effectively predicts post-RFCA recurrence in atrial fibrillation and heart failure patients,offering a useful tool for early assessment of recurrence risk.

Objective To investigate the prognostic value of triglyceride-glucose index(TyG index)in non-diabetic patients with acute coronary syndrome(ACS)who underwent percutaneous coronary intervention(PCI).Methods A total of 529 non-diabetic ACS patients who had successfully underwent PCI in our hospital from January 2019 to December 2020 were selected.According to the median TyG index(8.98),the patients were divided into low TyG index group(TyG＜8.98)and high TyG index group(TyG≥8.98).All the patients were followed up for major adverse cardiovascular events(MACE).Results Overall,55(10.4％)endpoint events were documented during a 24-month follow-up.Kaplan-Meier survival curves showed that the cumulative incidence of MACE was significantly higher in patients in the high TyG group than in the low TyG group(Log Rank P=0.001).Multivariate Cox analysis showed that after adjusting other confounding factors,TyG index was an independent predictor of MACE(HR=3.50,95％CI:1.44-8.53,P＜0.01).The risk of MACE in the high TyG group was 1.12-fold increased compared with the low TyG group(95％CI:1.19-3.79,P=0.011).The subgroup analysis results were generally consistent.Conclusion TyG index is an independent predictor of MACE in non-diabetic ACS patients who underwent PCI.

Objective:To evaluate the safety and efficacy of digital technology-assisted debridement and bone and soft tissue reconstruction in the treatment of chronic osteomyelitis of the tibia.Methods:This retrospective study analyzed clinical data from 38 patients (26 males, 12 females; mean age 45.61±18.36 years, range 16-83 years) with chronic post-traumatic osteomyelitis complicated by soft tissue defects in the tibia, treated at the Department of Orthopaedics, Fourth Medical Center of PLA General Hospital between June 2021 and June 2023. There were 18 cases of traffic accidents, 6 cases of high-altitude falls, 6 cases of heavy objects and 6 cases of low-energy falls. Lesion sites: 12 cases in the upper segment of the tibia, 12 cases in the middle segment, and 14 cases in the lower segment. According to the Cierny-Mader classification, there were 24 cases of type III and 14 cases of type IV. Before the operation, the "3D point cloud technology" was used to plan the debridement range of bone and soft tissue. During the operation, the optical navigation system was used to monitor the debridement range in real time. The flap was designed by combining "Reading Tablet Treasure" with CT angiography, and the amount of bone graft was predicted by AI algorithm. The surgical method adopted is the Masquelet technique, namely thorough debridement, bone cement occupation and soft tissue repair in the first stage, and bone reconstruction in the second stage. Comparing the calculated bone defect amount and soft tissue defect area before the operation with the actual measured values after debridement. The cure rate of infection was evaluated by using the McKee bone infection treatment criteria after the operation. The visual analogue scale (VAS) for pain, lower extremity functional scale (LEFS), and self-rating anxiety scale (SAS) were used to evaluate the improvement of the quality of life of postoperative patients.Results:38 patients were followed up with a mean follow-up of 13.53±2.37 months. 37 patients' infections were effectively controlled, and 1 patient had a recurrence of infection, with an effectiveness rate of 97% for the treatment of McKee's infections. The preoperative calculated bone defect amount and soft tissue defect area were 51.05±26.31 cm 3 and 68.42±43.45 cm 2 respectively, and the actual measured values after debridement during the operation were 51.66±26.35 cm 3 and 68.82±43.76 cm 2 respectively. There was no statistically significant difference before and after the operation ( P>0.05). The interval between the first and second stage surgeries was 10.36±1.61 weeks, and all flaps survived after the first stage surgery. Two months after the operation, one case had recurrent osteomyelitis. After palliative treatment, sinus tracts were formed at the infection site. At the 12-month regular dressing change follow-up, there were still purulent secretions in the sinus tracts. There was no recurrence of infection after primary debridement in 37 cases, and the bone grafts healed. The bone healing time was 3.58±0.97 months. The postoperative VAS, LEFS, and SAS scores were 1.00±0.91, 66.68±7.91, and 34.30±4.29, respectively, which were significantly improved compared with the preoperative scores of 7.54±1.52, 21.22±4.29, and 52.70±6.74, respectively, and the difference was statistically significant ( P<0.05). Conclusions:The application of digital technology to precisely design the debridement range of bone and soft tissue, and the real-time holographic visualization monitoring of the debridement range during the operation can achieve precise debridement of bone and soft tissue and personalized and precise repair of soft tissue defects. It is a safe and effective technique for the treatment of chronic osteomyelitis of the tibia.

Objective To develop and validate a nomogram model for predicting recurrence after radiofre-quency catheter ablation(RFCA)in patients with atrial fibrillation and heart failure using body surface electrocar-diogram indicators and clinical indicators.Methods We retrospectively analyzed 305 patients with atrial fibrilla-tion complicated with heart failure who underwent RFCA from January 2019 to January 2024.Patients were random-ized into training set(213 cases)and validation set(92 cases)at a ratio of 7:3 and followed up for at least 1 year.Based on the recurrence status,the patients were divided into recurrence group and non-recurrence group,with body surface electrocardiogram indicators and clinical indicators collected.Multivariate logistic regression analysis identified for risk factors for post RFCA recurrence,which were used to construct a nomogram.Model performance was assessed using the area under the receiver operating characteristic curve(AUC),Hosmer-Lemeshow test,calibration curves,and decision curve analysis(DCA).Results Among the 305 patients,84(27.54％)experi-enced recurrence after treatment.In the training set,61 patients had recurrence and 152 did not.No statistical differences were observed between the training set and the validation set(all P>0.05).In the training set,the recurrence group exhibited a higher proportion of persistent atrial fibrillation and significantly higher CHA2DS2-VASc scores,larger left atrial diameter,longer PR interval,and higher levels of NLR and NT-proBNP compared to the non-recurrence group(all P<0.05).Multivariate stepwise regression analysis revealed that high CHA2DS2-VASc score,long left atrial diameter,prolonged PR interval,and high NLR were independent risk factors of recurrence after RFCA(P<0.05)A four-factor prediction model was established as:Ln(P/1-P)=-12.87+0.84*CHA2DS2-VASc score+0.11* left atrial diameter+0.03*PR interval+0.31*NLR.The training and validation models showed AUCs of 0.85(95％CI:0.80～0.91)and 0.85(95％CI:0.76～0.94),respectively,suggesting that the model had good predictive efficiency.Hosmer-Lemeshow test results(χ2=2.43,P=0.965 for the training set;χ2=5.30,P=0.725 for the validation set)confirmed model fit,indicating that the fitted probability value was consistent with the actual probability value.Calibration curves after 1 000 times of Bootstrap repeated sampling showed the bias calibration curves of the training set and the validation set had good consistency with the actual curves,both close to the ideal curve.DCA revealed clinical utility across a wide threshold probability range(0.02～1.0 for the training set;0.04～1.0 for the validation set).Conclusion This nomogram,based on body surface electrocardiogram indicators and clinical indicators,effectively predicts post-RFCA recurrence in atrial fibrillation and heart failure patients,offering a useful tool for early assessment of recurrence risk.

ObjectiveTo investigate whether the effect of Taohong Siwutang on cerebral ischemia-reperfusion （CIRI） injury in rats is related to the regulation of astrocyte polarization and explore the related mechanism. MethodsEighty-four male SD rats were randomly assigned to the following groups： A sham operation group， a model group， Taohong Siwutang treatment groups （low dose， medium dose， and high dose）， ligustrazine phosphate tablet （LPT） group， and AG490 group. All groups， except for the sham operation group， underwent middle cerebral artery occlusion/reperfusion （MCAO/R） modeling and were treated for seven days. The neurological impairment was evaluated using the Longa score. The volume of cerebral infarction was assessed through 2，3，5-triphenyltetrazolium chloride （TTC） staining. Real-time fluorescent quantitative polymerase chain reaction （Real-time PCR） and Western blot analyses were performed to analyze the mRNA and protein expression levels of cortical complement 3 （C3）， S100 calcium-binding protein A10 （S100A10）， Janus kinase 2 （JAK2）， and signal transducer and activator of transcription 3 （STAT3）. Additionally， protein expression levels of vascular endothelial growth factor-A （VEGF-A） were assessed， and the mRNA expression levels of inflammatory factors， including interleukin-6 （IL-6）， interleukin-1β （IL-1β）， and tumor necrosis factor-α （TNF-α）， were evaluated. Glial fibrillary acidic protein （GFAP） and C3， S100A10 and Co-localization was detected via immunofluorescence double staining. Lastly， VEGF expression levels were measured using enzyme-linked immunosorbent assay （ELISA）. ResultsCompared with the sham operation group， the model group showed a significant increase in cerebral infarction volume and neurological impairment （P<0.01）. C3 protein levels were elevated， while S100A10 levels were decreased. Pathway-related markers were significantly upregulated （P<0.05， P<0.01）， and VEGF-A protein levels were significantly reduced （P<0.01）. The mRNA expression of inflammatory factors was significantly upregulated （P<0.01）. Co-localization analysis showed significantly increased GFAP and C3 fluorescence intensity （P<0.01） and greatly decreased GFAP and S100A10 fluorescence intensity （P<0.01）. Additionally， VEGF content was significantly elevated （P<0.01）. Compared with the model group， medium- and high-dose Taohong Siwutang and LPT groups exhibited a significant reduction in cerebral infarction volume and neurological impairment （P<0.01）. Groups treated with low， medium， and high doses of Taohong Siwutang and LPT group exhibited a decrease in C3 protein expression levels and an increase in S100A10 expression levels （P<0.01）. In the high-dose Taohong Siwutang and AG490 groups， both protein and mRNA expression of C3 and pathway-related markers were significantly downregulated （P<0.05， P<0.01）， while S100A10 expression and VEGF-A protein levels were significantly increased （P<0.01）. Additionally， the mRNA expression levels of inflammatory factors were significantly reduced （P<0.01）. The co-localization fluorescence intensity of GFAP and C3 significantly decreased （P<0.01）， while that of GFAP and S100A10 greatly increased （P<0.01）. Furthermore， VEGF content exhibited a marked elevation （P<0.01）. ConclusionTaohong Siwutang exerts a protective effect in rats with cerebral CIRI injury. The underlying mechanism is associated with the downregulation of the JAK2/STAT3 signaling pathway， promotion of A2-type astrocyte polarization， reduction of inflammatory factor release， and enhancement of VEGF production.

ObjectiveTo investigate whether the effect of Taohong Siwutang on cerebral ischemia-reperfusion （CIRI） injury in rats is related to the regulation of astrocyte polarization and explore the related mechanism. MethodsEighty-four male SD rats were randomly assigned to the following groups： A sham operation group， a model group， Taohong Siwutang treatment groups （low dose， medium dose， and high dose）， ligustrazine phosphate tablet （LPT） group， and AG490 group. All groups， except for the sham operation group， underwent middle cerebral artery occlusion/reperfusion （MCAO/R） modeling and were treated for seven days. The neurological impairment was evaluated using the Longa score. The volume of cerebral infarction was assessed through 2，3，5-triphenyltetrazolium chloride （TTC） staining. Real-time fluorescent quantitative polymerase chain reaction （Real-time PCR） and Western blot analyses were performed to analyze the mRNA and protein expression levels of cortical complement 3 （C3）， S100 calcium-binding protein A10 （S100A10）， Janus kinase 2 （JAK2）， and signal transducer and activator of transcription 3 （STAT3）. Additionally， protein expression levels of vascular endothelial growth factor-A （VEGF-A） were assessed， and the mRNA expression levels of inflammatory factors， including interleukin-6 （IL-6）， interleukin-1β （IL-1β）， and tumor necrosis factor-α （TNF-α）， were evaluated. Glial fibrillary acidic protein （GFAP） and C3， S100A10 and Co-localization was detected via immunofluorescence double staining. Lastly， VEGF expression levels were measured using enzyme-linked immunosorbent assay （ELISA）. ResultsCompared with the sham operation group， the model group showed a significant increase in cerebral infarction volume and neurological impairment （P<0.01）. C3 protein levels were elevated， while S100A10 levels were decreased. Pathway-related markers were significantly upregulated （P<0.05， P<0.01）， and VEGF-A protein levels were significantly reduced （P<0.01）. The mRNA expression of inflammatory factors was significantly upregulated （P<0.01）. Co-localization analysis showed significantly increased GFAP and C3 fluorescence intensity （P<0.01） and greatly decreased GFAP and S100A10 fluorescence intensity （P<0.01）. Additionally， VEGF content was significantly elevated （P<0.01）. Compared with the model group， medium- and high-dose Taohong Siwutang and LPT groups exhibited a significant reduction in cerebral infarction volume and neurological impairment （P<0.01）. Groups treated with low， medium， and high doses of Taohong Siwutang and LPT group exhibited a decrease in C3 protein expression levels and an increase in S100A10 expression levels （P<0.01）. In the high-dose Taohong Siwutang and AG490 groups， both protein and mRNA expression of C3 and pathway-related markers were significantly downregulated （P<0.05， P<0.01）， while S100A10 expression and VEGF-A protein levels were significantly increased （P<0.01）. Additionally， the mRNA expression levels of inflammatory factors were significantly reduced （P<0.01）. The co-localization fluorescence intensity of GFAP and C3 significantly decreased （P<0.01）， while that of GFAP and S100A10 greatly increased （P<0.01）. Furthermore， VEGF content exhibited a marked elevation （P<0.01）. ConclusionTaohong Siwutang exerts a protective effect in rats with cerebral CIRI injury. The underlying mechanism is associated with the downregulation of the JAK2/STAT3 signaling pathway， promotion of A2-type astrocyte polarization， reduction of inflammatory factor release， and enhancement of VEGF production.