Deep vein thrombosis (DVT) is a common complication after orthopedic surgery. This prospective observational study evaluated whether a single preoperative baseline measurement of the venous circumference-squared-to-area ratio (C2/A), alone and with D-dimer, was associated with DVT detected during the first 7 postoperative days. One hundred fifty adults undergoing orthopedic surgery were enrolled; 37 developed DVT and 113 did not. Preoperative circumference (C) and area (A) were measured separately at end-expiration with the ultrasound system's built-in measurement package during the same acquisition cycle. Investigators calculated C2/A as C2 divided by A. To apply this rule consistently to the retained participant-level dataset, all revision analyses used C2/A recalculated from the retained C and A fields. Postoperative ultrasound was performed at 12-h intervals for 7 days under a prespecified intensified study-surveillance schedule used only for outcome ascertainment. The areas under the receiver operating characteristic curves were 0.893 for common femoral vein C2/A, 0.817 for superficial femoral vein C2/A, 0.906 for popliteal vein C2/A, and 0.834 for D-dimer. The originally specified superficial femoral vein C2/A plus D-dimer model had an apparent area under the curve of 0.887 and a stratified 5-fold cross-validated out-of-fold area under the curve of 0.877. A 5-variable exploratory model had an out-of-fold area under the curve of 0.938. Using cohort-derived thresholds of 16.26 for superficial femoral vein C2/A and 2.15 mg/L FEU for D-dimer, DVT occurred in 0 of 78 patients with neither marker elevated, 15 of 50 with one elevated, and 22 of 22 with both elevated. Preoperative venous C2/A and D-dimer were associated with early postoperative DVT, but the thresholds and models are exploratory and require external validation.

Background:Although successful recanalization of the occluded artery is achieved, no-reflow phenomenon (NRP) becomes a main contributor to poor prognosis in patients with acute ischemic stroke. There are some laboratory results to represent biomarkers of the no-reflow phenomenon. However, few studies have characterized the metabolomic signature of NRP. Using high-performance liquid chromatography-tandem mass spectrometry (LC-MS)-based method, this study aims to characterize the plasma metabolites associated with NRP. Methods:A total of 34 patients with acute large vessel occlusion in anterior circulation who underwent successful thrombectomy with final angiographic expanded Treatment in Cerebral Infarction score of 2c-3 score were enrolled (19 without NRP and 15 with NRP). Fasting venous blood collected 24 h after the procedure was centrifuged and subjected to metabolomic analysis. Results:We identified 29 differentially expressed plasma metabolites, the majority of which were phosphatidylcholine (PC) species. Among them, PC(20:4(5Z,8Z,11Z,14Z)/P-16:0) showed the most significant alteration and exhibited robust predictive performance (AUC = 0.846). The most prominently disrupted metabolic pathway was glycerophospholipid metabolism, particularly PC-mediated pathways, which appeared to play a central role in the association with of NRP. Conclusion:This study depict the plasma metabolic profile of NRP patients following stroke thrombectomy, and discover that phosphatidylcholine-dominated metabolites and related pathways may play a potential role in the occurrence of NRP. These metabolic biomarkers demonstrate promising discriminative ability and may help identify high-risk patients at an early stage, providing new targets for mechanism research and therapeutic intervention.

Among patients with acute ischemic stroke (AIS) secondary to large vessel occlusion (LVO) who undergo successful reperfusion following endovascular thrombectomy (EVT), only one-third are disability-free at 90 days, which may be related to persistent microvascular hypoperfusion after thrombectomy known as the “no-reflow phenomenon”. Adenosine is administered to prevent percutaneous coronary intervention (PCI)-related no-reflow through microvasculature dilation and neutrophil-mediated inflammation modulation. However, its role in in the setting of AIS has not been clearly elucidated. To evaluate the safety and efficacy of adjunctive intra-arterial adenosine following successful EVT in LVO patients. In this multicenter, open-label, randomized, phase 2 trial, we evaluated the safety and efficacy of adjunctive intra-arterial adenosine following successful EVT in AIS patients. Up to 160 eligible stroke patients with anterior intracranial large vessel occlusion presenting within 24 hours from symptom onset (time last known well) are planned to be consecutively randomized. The primary outcome was the shift in the distribution of mRS scores at 90 days. Safety outcomes included symptomatic intracranial hemorrhage (sICH) within 48 hours and mortality at 90 days. This pivotal trial will provide first-hand data on the efficacy and safety of adjunctive intra-arterial adenosine following successful EVT in patients with acute ischemic stroke due to LVO. ChiCTR2400092051 ( www.chictr.org.cn ).

Angiogenesis is crucial to improving neurovascular remodeling poststroke. Therein, the transformation of endothelial cells (ECs) to tip cells is essential in initiating angiogenesis. Mitochondrial damage in ECs poststroke and associated metabolic disorder are key factors repressing angiogenesis, but the mechanisms are unknown. Here, we designed an Arg-Gly-Asp peptide (RGD)-modified, mitochondria-enriched, and extracellular vesicle mimetics (mitoEVMs) platform for mitochondrial transfer. RGD mediated the mesenchymal stem cell-derived mitochondria transfer to ECs around the lesion targetedly. We found MSC-derived mitochondria promoted tip cell transition and further stimulated angiogenesis after stroke, alleviated brain atrophy, and improved functional rehabilitation. We noticed mitochondrial transfer rescued mitochondrial function in ECs and reprogrammed glutathione metabolism to activate the mTORC1 pathway, upregulated the expression of p4E-BP1 and VEGFR2, and ultimately facilitated tip cell transition. Our work elucidates the mechanism of MSC-derived mitochondrial transfer in poststroke treatment and proposes a potential approach for rehabilitation after stroke.

Acute ischemic stroke remains a significant health concern owing to the limited efficacy of current therapeutic options. In recent years, Neuregulin-1 has exhibited promising neuroprotective effects in cerebral ischemia. However, the sources and functions of Neuregulin-1 have not yet been fully understood, which hinders its translation and broad application. Here, we collected paired clot and peripheral blood samples from patients with acute ischemic stroke to determine the sources of Neuregulin-1. In addition, we established an in vivo transient middle cerebral artery occlusion mouse model to investigate the therapeutic effects of Neuregulin-1 and its underlying molecular biological mechanisms. We observed a significant elevation in serum Neuregulin-1 levels among patients with acute ischemic stroke that correlated with severity of neurological impairment and clinical outcome. Using single-cell sequencing, we identified Neuregulin-1-positive macrophages among peripheral blood mononuclear cells that produced Neuregulin-1 post-ischemia. In addition, Neuregulin-1 promoted repair of the infarcted area, alleviating neuronal and myelin damage and improving overall behavioral recovery in mice. We found that Neuregulin-1 may exert these neuroprotective effects by promoting angiogenesis in the infarct area, and that this effect is mediated by Akt/mTOR/VEGF-dependent signaling. Our findings suggest that peripheral macrophages are a source of Neuregulin-1 post-stroke. Neuregulin-1 exerts its neuroprotective effects by promoting angiogenesis via Akt/mTOR/VEGF-dependent signaling, showing promising clinical translation potential.

The body weight-based thrombolytic medication strategy in clinical trials shows critical defects in recanalization rate and post-thrombolysis hemorrhage. Methods for perceiving thrombi heterogeneity of thrombolysis resistance is urgently needed for precise thrombolysis. Here, we revealed the relationship between the thrombin heterogeneity and the thrombolysis resistance in thrombi and created an artificial biomarker-based nano-patrol system with robotic functional logic to perceive and report the thrombolysis resistance of thrombi. The nano-patrols are contrallable and are able to accomplish thrombolysis resistance-matched personalized and precise therapy according to the feedback signal from artificial biomarkers. This nano-patrol system depicted more enhanced thrombolytic efficiency (elevated by 25%) than alteplase for mini pig model and clinical thrombi and achieved recanalization in thrombotic model where alteplase encountered failure. Moreover, the nano-patrol remarkably reduced the infarct volume and the hemorrhagic transformation risk (0.12-fold of alteplase) of cerebral thrombosis. Therefore, we developed a unique tool for diagnosing thrombolysis resistance and achieving personalized and precise thrombolysis.

There is no effective and noninvasive solution for thrombolysis because the mechanism by which certain thrombi become tissue plasminogen activator (tPA)-resistant remains obscure. Endovascular thrombectomy is the last option for these tPA-resistant thrombi, thus a new noninvasive strategy is urgently needed. Through an examination of thrombi retrieved from stroke patients, we found that neutrophil extracellular traps (NETs), ε-(γ-glutamyl) lysine isopeptide bonds and fibrin scaffolds jointly comprise the key chain in tPA resistance. A theranostic platform is designed to combine sonodynamic and mechanical thrombolysis under the guidance of ultrasonic imaging. Breakdown of the key chain leads to a recanalization rate of more than 90% in male rat tPA-resistant occlusion model. Vascular reconstruction is observed one month after recanalization, during which there was no thrombosis recurrence. The system also demonstrates noninvasive theranostic capabilities in managing pigs’ long thrombi (>8 mm) and in revascularizing thrombosis-susceptible tissue-engineered vascular grafts, indicating its potential for clinical application. Overall, this noninvasive theranostic platform provides a new strategy for treating tPA-resistant thrombi. There is no noninvasive solution for tPAresistant thrombi as the mechanism remains obscure. Here, the authors show a constructed ultrasound-responsive theranostic platform for real-time monitoring and efficient thrombolysis by breaking the keychain in tPA-resistant thrombi.

Background Diagnosis of the cause of cerebral thrombi is vital for recurrence prevention but also challenging. The presence of the microbiome has recently been confirmed in thrombus, suggesting a novel approach to distinguish cerebral thrombi of different origins. However, little is known about whether there is heterogeneity in microbiological colonization of cerebral thrombi of different sources. Methods and Results Forty patients experiencing acute ischemic stroke were included and clinical data were collected. Metagenomic next‐generation sequencing was adopted to detect bacterial and genomic signatures of human cerebral thrombi samples. We found similar species diversity between the large‐artery atherosclerosis thrombi and cardioembolic thrombi but different species composition and distribution of cerebral thrombus microbiota. Compared with the group with cardioembolism, the group with large‐artery atherosclerosis showed a significantly higher relative abundance of Ralstonia insidiosa among the top 10 bacterial species in cerebral thrombi. Twenty operational taxonomy units were correlated with 11 clinical indicators of ischemic stroke. The Gene Ontology enrichment analysis revealed 9 different enriched biological processes (translation and carbohydrate metabolic process, etc). The enriched Kyoto Encyclopedia of Genes and Genomes pathways included ribosome, butanoate metabolism, and sulfur metabolism. Conclusions This study, based on the approach of metagenomic next‐generation sequencing, provides a diagnostic microbiological method to discriminate individuals with cardioembolic thrombi from those with large‐artery atherosclerosis thrombi with human cerebral thrombi samples. Our findings provide a fresh perspective on microbial heterogeneity of cerebral thrombi and demonstrate biological processes and pathway features of cerebral thrombi.

OBJECTIVE: This study aimed to evaluate consecutive patients with chronic venous insufficiency (CVI) describing the relationship between Clinical/Etiological/Anatomical/Pathophysiological (CEAP) classification, leg heaviness/ache/swelling/throbbing/itching (HASTI) score, and Venous Clinical Severity Score (VCSS) and assessing the correlation between them. MATERIALS AND METHODS: The CEAP classification, HASTI, and VCSS of consecutive patients were recorded, and their correlations were evaluated. RESULTS: Four hundred eighty-four consecutive patients from March 2018 to March 2019 were studied. Significant correlations were detected between the HASTI and CEAP classification ( F = 16.558, P < 0.001) and between VCSS and CEAP classification ( F = 57.073, P < 0.001). The VCSS correlated more positively with CEAP (Spearman's correlation coefficient r = 0.740, P < 0.001) than HASTI (Spearman's correlation coefficient r = 0.536, P < 0.001). Using CEAP ≥2 as the cutoff, the areas under the receiver operating characteristics curve of the HASTI and VCSS were 0.694 and 0.774, respectively ( P < 0.001 or both). The HASTI and VCSS cutoff values of 6.50 and 4.50, respectively, were identified as indicators of significant CVI with corresponding sensitivities of 63.8% and 78.7% and specificities of 65.6% and 47.0%, respectively. CONCLUSION: Increasing HASTI and VCSS corresponded to increasing CEAP class in patients with CVI. The result may be applicable for early screening of patients with CVI.

Objectives: Hemodynamic changes in C-0 to C-2 according to the clinical/etiological/anatomical/pathophysiological classification have not been analyzed extensively. We intend to investigate the characteristics of early stage venous disease using venous clinical severity score (VCSS), heaviness/ache/swelling/throbbing/itching (HASTI) score and duplex ultrasound (DUS) derived parameters. Methods: From Aug. 2020 to Jul. 2021, consecutive patients were categorized according to the clinical/etiological/anatomical/pathophysiological 2020 classification. The vein diameter (mm), reflux time (s), cross-sectional area (cm 2 ), peak and mean reflux velocity (cm/s), and total reflux volume (mL) were documented in the superficial system and deep system. VCSS and HASTI scores were assessed and DUS parameters were analyzed. A P value of less than .05 was considered statistically significant. Results: We studied 257 consecutive patients (142 female) with 371 limbs. The mean age was 50.96 +/- 13.27 years (range, 20-81 years; median, 53 years) with an average body mass index of 24.03 +/- 2.96 kg/m(2) (range, 17.00-33.06 kg/m(2); median, 23.67 kg/m(2)). The proportion of clinical (C) category was as followed: 47 C-0s (12.67%), 45 C-1 (12.13%), and 279 C-2 (75.20%). There were 42.6% of C-0 and 62.2% of C-1 associated with some form of venous reflux, Pr (pathology [P]-reflux). Reflux of the great saphenous vein above the knee (GSVa) was the most commonly affected vein segment from C0-2. C-1 differed from C o only by age and severity scores with a cut-off value of 1 for both VCSS and HASTI. Larger saphenous veins diameter (GSV and small saphenous vein) were seen in Pr (P-reflux) than Pn (P-none) of C-0 cases. Larger deep vein diameters (common femoral vein, femoral vein, and popliteal vein) were evident in Pr versus Pn of C-1 cases. In C-2, the popliteal vein, saphenofemoral junction, and GSVa were dilated in Pr cases. Conclusions: Both HASTI and VCSS were discriminative from C-0 to C-2. C-0 differed from C-1 by age and severity scores as DUS characteristics were not significantly different between the two groups. Vessel diameter played a discriminative role in distinguishing Pn versus Pr cases in each C(0-2 )category. GSVa was the most frequent reflux segment irrespective of reflux types.

In clinical applications, the classification of ultrasound images needs to be processed as an aid to diagnosis. Based on this, a hybrid model of cascaded deep convolutional neural network consisting of two different CNNs and a new classification method are designed and evaluated for its feasibility and effectiveness in ultrasound image classification. A total of 1000 pathological slides of patients with thyroid nodular lesions kept in the Department of Pathology of the First Affiliated Hospital of Lanzhou University, China, were retrospectively collected. After image acquisition, the images were randomly divided into training set, validation set, and test set in the ratio of 4 : 3 : 3. Three convolutional neural network models (VGG 19 model, Inception V3 model, and DenseNet 161 model) with pretraining parameters acquired on the training set were trained, and the models were combined to construct an integrated learning model, and the performance of the models in recognizing pathological images was evaluated based on the test set data. The experimental results show that the VGG 19 model is less effective in classification, with a correct rate of 88.20%, which is lower than that of Inception V3 and DenseNet161 models (92.87% and 92.95%). InceptionV3 and DenseNet161 models have significant advantages in terms of accuracy, number of parameters, and training efficiency, where the DenseNet161 model has faster convergence and better generalization performance, but occupies more video memory in the operation; moreover, the DenseNet161 operation time (1986.48 s) and response time (16 s) are better than the other two models. In addition, the integrated learning of InceptionV3 and DenseNet161 can improve the recognition of pathological images by a single model. Compared with other methods, the performance of the cascaded CNNs proposed in this study is significantly improved, and the multiview strategy can improve the performance of cascaded CNNs. The experimental results demonstrate the potential clinical application of cascaded CNNs, which can provide physicians with an objective second opinion and reduce their heavy workload, in addition to making the diagnosis of thyroid nodules easy and reproducible for people without medical expertise.

INTRODUCTION: The goal of this study was to characterize consecutive patients in Northwest China treated with endovenous radiofrequency ablation (RFA) and foam sclerotherapy over a 10-month period in 2020. METHODS: A total of 55 (31 men) patients were analyzed. An ultrasound examination was performed preprocedure and at set intervals up to 6 months postprocedure. The clinical-etiological-anatomical-pathophysiological classification, Venous Clinical Severity Score (VCSS), and heaviness, achiness, swelling, throbbing, and itching (HASTI) score were used. RESULTS: Ultrasound confirmed 23 (41.8%) patients had unilateral disease and 32 (58.2%) had bilateral disease. Of the total 87 limbs, C2 predominated (42;48.3%). At 6 months postprocedure, VCSS improved in the C2, C4, C5, and C6 classes ( P < 0.001); HASTI improved in the C2, C3, C4, and C5 classes ( P < 0.001). CONCLUSION: This is one of the few clinical characterizations of patients who had RFA and foam sclerotherapy in Northwest China. Overall, both the VCSS and the HASTI score demonstrated improvement postintervention.

Thrombus components are dynamically influenced by local blood flow and blood immune cells. After a large-vessel occlusion stroke, changes in the cerebral thrombus are unclear. Here we assessed a total of 206 cerebral thrombi from patients with ischemic stroke undergoing endovascular thrombectomy. The thrombi were categorized by time to reperfusion of <4 h (T4), 4–8 h (T4–8), and >8 h (T8). The cellular compositions in thrombus were analyzed, and relevant clinical features were compared. Both white blood cells and neutrophils were increased and then decreased in thrombus with time to reperfusion, which were positively correlated with those in peripheral blood. The neutrophil extracellular trap (NET) content in thrombus was correlated with the degree of neurological impairment of patients. Moreover, with prolonged time to reperfusion, the patients showed a trend of better collateral grade, which was associated with a lower NET content in the thrombus. In conclusion, the present results reveal the relationship between time-related endovascular immune response and clinical symptoms post-stroke from the perspective of thrombus and peripheral blood. The time-related pathological changes of cerebral thrombus may not be the direct cause for the difficulty in thrombolysis and thrombectomy. A low NET content in thrombi indicates excellent collateral flow, which suggests that treatments targeting NETs in thrombi might be beneficial for early neurological protection.

Objective: Our goal was to summarize the relationship between vein diameters, reflux characteristics, and clinical severity in consecutive patients with chronic venous insufficiency (CVI) in Northwest China. Methods: We evaluated 531 consecutive patients with CVI (249 women) who presented to the Department of Ultrasound of Xijing Hospital from September 2017 to July 2019. Reflux times and the mean diameters of the great saphenous, the small saphenous, and the calf perforator veins based on duplex ultrasound scans obtained in the standing position were recorded. Venous-specific assessment tools-the Heaviness, Achiness, Swelling, Throbbing, Itching (HASTI) score, the Venous Clinical Severity Score (VCSS), and the Clinical, Etiological, Anatomical, Pathophysiological (CEAP) class-were analyzed. Regression analysis was used to investigate the relationship between the clinical scores, vein diameters, and reflux times. A P value of less than.05 was considered statistically significant. Results: We analyzed 531 consecutive patients with 728 limbs. The mean age was 55.24 +/- 11.38 years; the mean body mass index (BMI) was 24.75 +/- 3.49 kg/m(2). Three hundred thirty-four patients (62.9%) presented with unilateral limb findings and 197 (37.1%), with bilateral limb involvement. No significant changes were noted in age and BMI across CEAP classes (F = 2.322 and F = 3.917, respectively; P >.05 for both). Both the HASTI score (r(2) = 0.8741; P <.001) and the VCSS (r(2) = 0.9257; P <.001) correlated with the CEAP class. The HASTI score strongly correlated with the mean diameters of the great saphenous and small saphenous veins (r(2) = 0.9252, r(2) = 0.6304, respectively; P <.001 for both) similarly to VCSS (r(2) = 0.9396, r(2) = 0.7195, respectively; P <.001 for both). The HASTI score and VCSS correlated equally with the mean diameters of the calf perforator veins (r = 0.7773 and r = 0.7781, respectively; P <.001 for both). In those with C6, both great saphenous vein (F = 4.608; P <.001) and small saphenous vein reflux times (F = 14.97; P <.001) were significantly higher than those in C1. Both the HASTI score and VCSS strongly associated with the reflux times of the great saphenous (r(2) = 0.7706 and r(2) = 0.8181, respectively; P <.001 for both) and small saphenous veins (r(2) = 0.6470 and r(2) = 0.7865, respectively; P <.001 for both). Conclusions: This analysis is one of the few epidemiologic studies of patients with CVI in Northwest China. Age and BMI did not correlate with CEAP class. Both the HASTI score and VCSS correlated strongly with the CEAP classification; vein diameters and reflux time in both the great saphenous vein and the small saphenous vein, indicating the validity of these outcome tools to venous hemodynamics and to CVI in general.

OBJECTIVES This study aimed to evaluate the validity of the risk assessment model (RAM) of Caprini and Padua in identifying venous thromboembolism (VTE) among hospitalized medical patients. METHODS This retrospective study reviewed a total of 320 VTE and 320 non-VTE patients. Baseline demographics and clinical data of these patients were all recorded. The Caprini and Padua RAMs were implemented and the individual scores of each risk factor were summed to generate a cumulative risk score. Meanwhile, the sensitivity, specificity, and positive and negative predictive values of these two models were analysed. Receiver operating characteristic (ROC) curve was plotted to calculate the area under the curve (AUC) and the Youden index. RESULTS Significant differences were observed in risk factors between VTE and non-VTE patients. More VTE patients were classified into the high-superhigh risk level by the Caprini RAM than the Padua RAM (70.9 vs 23.4%, P < 0.01). The sensitivity and positive and negative predictive values in the Caprini RAM were higher than those in the Padua RAM (P < 0.05). However, the specificity of the Caprini RAM was lower than that of the Padua RAM (P < 0.01). The AUC and the Youden index were higher in the Caprini RAM than in the Padua RAM (P < 0.01), whereas the Youden index in the Padua RAM at critical point 4 was lower than that at critical point 3 (0.010 vs 0.140, P < 0.05). CONCLUSIONS The Caprini RAM was suggested to be more effective than the Padua RAM for identification of hospitalized medical patients at risk for VTE.

Objective To investigated the current situation and to explore the risk factors of venous thromboembolism ( VTE) among inpatients according to the retrospective analysis. Methods 539 VTE patients who had treated in a grade III class A hospital in Shanghai during September 2011 to September 2014 were chosen as the case group. The control group included patients who had no VTE but treated in the same hospital during that time. The clinical data of the participants were collected and retrospectively analyzed.Results Univariate analysis demonstrated significant differences in age ( t=5.421, P<0.05) , BMI>25 kg/m2 , major surgery, malignancy, VTE history, pneumonia, central venous catheter, stay in bed>72 h, stroke, immobilization, pelvis/lower extremity fractures, and joint arthroplasty between the two groups (χ2=9.868, 29.711, 16.230, 48.050,5. 613, 16.443, 5.735, 20.403, 4.340, 20.646, 10.343; P<0.05). Furthermore, the logistic regression analysis indicated that the risk factors of VTE were related to stroke[OR=6.414 (2.421,16.995)], joint arthroplasty [OR=5.718(1.268,25.777)], pelvic/lowers extremity fractures[OR=4.918 (2.074,11.659)], central venous catheters[OR=3.446 (1.671,7.107)], surgery history[OR=2.245 (1.338,3.767)], major surgery [ OR=2.189 ( 1. 553, 3. 085 ) ] , BMI>25 kg/m2 [ OR=1. 913 ( 1. 450, 2. 523 ) ] , malignancy [ OR=1. 713 (1. 184,2.477)], and age[OR=1.559 (1.343,1.810)].Conclusions More specific preventive strategies should be focused on and implemented to VTE patients as they suffered from various risk factors at the same time.