Nomogram to Predict 90-Day All-Cause Mortality in Acute Ischemic Stroke Patients after Endovascular Thrombectomy.

OBJECTIVE: Although Endovascular Thrombectomy (EVT) significantly improves the prognosis of Acute Ischemic Stroke (AIS) patients with large vessel occlusion, the mortality rate remains higher. This study aimed to construct and validate a nomogram for predicting 90-day all-cause mortality in AIS patients with large vessel occlusion and who have undergone EVT. METHODS: AIS patients with large vessel occlusion in the anterior circulation who underwent EVT from May 2017 to December 2022 were included. 430 patients were randomly split into a training group (N=302) and a test group (N=128) for the construction and validation of our nomogram. In the training group, multivariate logistic regression analysis was performed to determine the predictors of 90-day all-cause mortality. The C-index, calibration plots, and decision curve analysis were applied to evaluate the nomogram performance. RESULTS: Multivariate logistic regression analysis revealed neurological deterioration during hospitalization, age, baseline National Institutes of Health Stroke Scale (NIHSS) score, occlusive vessel location, malignant brain edema, and Neutrophil-to-lymphocyte Ratio (NLR) as the independent predictors of 90-day all-cause mortality (all p ≤ 0.039). The C-index of the training and test groups was 0.891 (95%CI 0.848-0.934) and 0.916 (95% CI: 0.865-0.937), respectively, showing the nomogram to be well distinguished. The Hosmer-Lemeshow goodness-of-fit test revealed the p-values for both the internal and external verification datasets to be greater than 0.5. CONCLUSION: Our nomogram has incorporated relevant clinical and imaging features, including neurological deterioration, age, baseline NIHSS score, occlusive vessel location, malignant brain edema, and NLR ratio, to provide an accurate and reliable prediction of 90-day all-cause mortality in AIS patients undergoing EVT.

STUB1 exacerbates calcium oxalate-induced kidney injury by modulating reactive oxygen species-mediated cellular autophagy via regulating CFTR ubiquitination.

The formation of calcium oxalate (CaOx) crystals in the kidneys leads to renal epithelial damage and the progression of crystalline nephropathy. This study investigated the role of STIP1 homology and U-box protein 1 (STUB1), an E3 ubiquitin ligase, and cystic fibrosis transmembrane conductance regulator (CFTR), a chloride channel, in CaOx-related renal damage and autophagy regulation. HK-2 cells were treated with various doses of CaOx monohydrate (COM) to simulate kidney injury in vitro. Cell viability, reactive oxygen species (ROS) production, and apoptosis were assessed. The regulation of CFTR ubiquitination by STUB1 was confirmed by immunoprecipitation. An in vivo model was established by injecting mice with glyoxylate. COM treatment dose-dependently decreased cell viability, increased TNF-α and ROS production, and induced apoptotic cell death in HK-2 cells. COM-treated cells also showed decreased CFTR protein expression. CFTR overexpression improved cell viability and reduced ROS production in COM-stimulated HK-2 cells. Bioinformatics analysis predicted CFTR's ubiquitination binding site for STUB1. Further analysis confirmed the role of STUB1 as a ubiquitin ligase in CFTR degradation. Knockdown of STUB1 upregulated CFTR expression, while STUB1 overexpression had the opposite effect. Knockdown of CFTR reversed the impact of STUB1 deficiency on autophagy. The in vivo experiments showed that CFTR overexpression attenuated kidney tissue damage and CaOx deposition in mice. STUB1-mediated CFTR ubiquitination plays a crucial role in mitigating calcium oxalate-related renal damage by regulating autophagy. Targeting the STUB1/CFTR axis may hold therapeutic potential for treating kidney injury associated with calcium oxalate deposition.

Steering Electron-Induced Surface Reaction via a Molecular Assembly Approach.

Electrons not only serve as a "reactant" in redox reactions but also play a role in "catalyzing" some chemical processes. Despite the significance and ubiquitousness of electron-induced chemistry, many related scientific issues still await further exploration, among which is the impact of molecular assembly. In this work, microscopic insights into the vital role of molecular assembly in tweaking the electron-induced surface chemistry are unfolded by combined scanning tunneling microscopy and density functional theory studies. It is shown that the selective dissociation of a C-Cl bond in 4,4″-dichloro-1,1':3',1''-terphenyl (DCTP) on Cu(111) can be efficiently triggered by an electron injection via the STM tip into the unoccupied molecular orbital. The DCTP molecules are embedded in different assembly structures, including its self-assembly and coassemblies with Br adatoms. The energy threshold for the C-Cl bond cleavage increases as more Br adatoms stay close to the molecule, indicative of the sensitive response of the electron-induced surface reactivity of the C-Cl bond to the subtle change in the molecular assembly. Such a phenomenon is rationalized by the energy shift of the involved unoccupied molecular orbital of DCTP that is embedded in different assemblies. These findings shed new light on the tuning effect of molecular assembly on electron-induced reactions and introduce an efficient approach to precisely steer surface chemistry.

Full-Scale Experimental and Field Investigations into Expansion Mechanism of Foamed Polyurethane and its Lifting Behaviors for Repair and Maintenance of Railway Slab Track Systems.

Excessive settlement of the subgrade seriously reduces the service quality of slab tracks and threatens trains' running safety. While the utilization of foamed polyurethane is recognized as an effective solution, previous research on its expansion mechanism and its impact on track lifting requires further refinement. Accordingly, a series of full-scale tests, including expansion force tests on foamed polyurethane with diverse qualities and lifting tests of polyurethane grouting with varied qualities on the track structure, have been conducted. The expansion development process of foamed polyurethane is meticulously elucidated, and key expansion parameters are analyzed. Simultaneously, this research explores the lifting behavior of foamed polyurethane grouting under the slab tracks, yielding new insights into essential lifting parameters for track formation repair and maintenance. Based on the experimental data, this study proposes new empirical formulas to comprehensively describe both the expansion mechanism of foam polyurethane and its lifting behavior under the slab tracks. The outcomes of this research offer a new breakthrough for the design of lifting mechanism for maintaining slab track structures through the utilization of foam polyurethane slurry grouting, such as determining the optimal grouting quantity. In addition, these results are instrumental to the evaluation of lifting effects and service life, enhancing the circular economy of railway track systems.

High-quality chromosome-level genome assembly of the Northern Pacific sea star Asterias amurensis.

Asterias amurensis, a starfish species that is native to countries such as China and Japan, as well as non-native regions like Australia, has raised serious concerns in terms of its impact on ecology and economy. To gain a better understanding of its population genomics and dynamics, we successfully assembled a high-quality chromosome-level genome of A. amurensis using PacBio and Hi-C sequencing technologies. A total of 87 scaffolds assembly with contig N50 length of 10.85 Mb and scaffold N50 length of 23.34 Mb were obtained, with over 98.80% (0.48 Gb) of them anchored to 22 pseudochromosomes. We predicted 16,673 protein-coding genes, 95.19% of which were functionally annotated. Our phylogenetic analysis revealed that A. amurensis and Asterias rubens formed a clade, and their divergence time was estimated ~ 28 million years ago (Mya). The significantly enriched pathways and Gene Ontology terms related to the amplified gene family were mainly associated with immune response and energy metabolism, suggesting that these factors might have contributed to the adaptability of A. amurensis to its environment. This study provides valuable genomic resources for comprehending the genetics, dynamics, and evolution of A. amurensis, especially when population outbreaks or invasions occur.

A real-time field bus architecture for multi-smart-motor servo system.

The multi-motor servo system (MMSS) is an electro-mechanical system widely used in various fields, including electric vehicles, robotics, and industrial machinery. Depending on the application, the number of motors in the system can range from several dozens to tens of thousands, which imposes additional communication demands. Thus, ensuring synchronization and control precision of the system requires addressing the challenge of guaranteeing the performance and reliability of communication among motors in the MMSS. In this paper, we design a smart servo motor (SSM) to upgrade the system to the multi-smart-motor servo system (MSMSS) based on a distributed real-time field bus architecture, namely, Multi-Motor Bus (MMB) architecture. The proposed MMB architecture is lightweight and stable, providing real-time support for Control Area Network connections to a central user computer and inter-integrated circuit connections to SSM units. This MMB architecture facilitates the synchronization of command transmission across SSMs and ensures the consistency of motors in the MSMSS. Additionally, a serial experiments to examine 3 key system performance and reliability characteristics are conducted, including command transmission time, transmission jitters, and rotation consistency. The analysis of these characteristics demonstrates the system's potential and feasibility to be applicable in industry.

The value of CT shape quantification in predicting pathological classification of lung adenocarcinoma.

OBJECTIVE: To evaluate whether quantification of lung GGN shape is useful in predicting pathological categorization of lung adenocarcinoma and guiding the clinic. METHODS: 98 patients with primary lung adenocarcinoma were pathologically confirmed and CT was performed preoperatively, and all lesions were pathologically ≤ 30 mm in size. On CT images, we measured the maximum area of the lesion's cross-section (MA). The longest diameter of the tumor (LD) was marked with points A and B, and the perpendicular diameter (PD) was marked with points C and D, which was the longest diameter perpendicular to AB. and D, which was the longest diameter perpendicular to AB. We took angles A and B as big angle A (BiA) and small angle A (SmA). We measured the MA, LD, and PD, and for analysis we derived the LD/PD ratio and the BiA/SmA ratio. The data were analysed using the chi-square test, t-test, ROC analysis, and binary logistic regression analysis. RESULTS: Precursor glandular lesions (PGL) and microinvasive adenocarcinoma (MIA) were distinguished from invasive adenocarcinoma (IAC) by the BiA/SmA ratio and LD, two independent factors (p = 0.007, p = 0.018). Lung adenocarcinoma pathological categorization was indicated by the BiA/SmA ratio of 1.35 and the LD of 11.56 mm with sensitivity of 81.36% and 71.79%, respectively; specificity of 71.79% and 74.36%, respectively; and AUC of 0.8357 (95% CI: 0.7558-0.9157, p < 0.001), 0.8666 (95% CI: 0.7866-0.9465, p < 0.001), respectively. In predicting the pathological categorization of lung adenocarcinoma, the area under the ROC curve of the BiA/SmA ratio combined with LD was 0.9231 (95% CI: 0.8700-0.9762, p < 0.001), with a sensitivity of 81.36% and a specificity of 89.74%. CONCLUSIONS: Quantification of lung GGN morphology by the BiA/SmA ratio combined with LD could be helpful in predicting pathological classification of lung adenocarcinoma.

Finite Element Analysis of the Effect for Different Thicknesses and Stitching Densities under the Low-Velocity Impact of Stitched Composite Laminates.

In this study, a progressive damage model was developed for the mechanical response and damage evolution of carbon fiber stitched composite laminates under low-velocity impact (LVI). The three-dimensional Hashin and Hou failure criteria were used to identify fiber and matrix damage. The cohesive zone model was adopted to simulate the delamination damage, combined with the linear degradation discounting of the equivalent displacement method to characterize the stiffness degradation of the material, and the corresponding user material subroutine VUMAT was coded. The finite element analysis of the LVI of stitched composite laminates under different energies was finished in Abaqus/Explicit. Furthermore, the simulation predictions matched well with the results of the experimental tests. Based on this, composite laminates' mechanical response and damage forms with different thicknesses and stitch densities were analyzed. The findings show that the main damages of composite laminates were matrix tensile damage and delamination. The stitching process could improve the impact tolerance of composite laminates, inhibiting delamination and reducing the area of the delamination damage. The higher the density of the stitching, the more noticeable its inhibition would be. The thickness of the laminate also had a more significant effect on the damage to the laminate. Thin plates were more prone to matrix tensile damage due to their lower flexural rigidity, whereas thick plates were more susceptible to delamination because of their higher flexural rigidity.

Fast Adversarial Training With Adaptive Step Size.

While adversarial training and its variants have shown to be the most effective algorithms to defend against adversarial attacks, their extremely slow training process makes it hard to scale to large datasets like ImageNet. The key idea of recent works to accelerate adversarial training is to substitute multi-step attacks (e.g., PGD) with single-step attacks (e.g., FGSM). However, these single-step methods suffer from catastrophic overfitting, where the accuracy against PGD attack suddenly drops to nearly 0% during training, and the network totally loses its robustness. In this work, we study the phenomenon from the perspective of training instances. We show that catastrophic overfitting is instance-dependent, and fitting instances with larger input gradient norm is more likely to cause catastrophic overfitting. Based on our findings, we propose a simple but effective method, Adversarial Training with Adaptive Step size (ATAS). ATAS learns an instance-wise adaptive step size that is inversely proportional to its gradient norm. Our theoretical analysis shows that ATAS converges faster than the commonly adopted non-adaptive counterparts. Empirically, ATAS consistently mitigates catastrophic overfitting and achieves higher robust accuracy on CIFAR10, CIFAR100, and ImageNet when evaluated on various adversarial budgets. Our code is released at https://github.com/HuangZhiChao95/ATAS.

Visual analysis of lung neuroendocrine tumors based on CiteSpace knowledge graph.

Objective: The relevant literatures in the field of pulmonary neuroendocrine tumor were analyzed to understand the lineage, hot spots and development trends of research in this tumor. Method: The Web of Science core collection was searched for English-language literature about neuroendocrine tumors of the lung published between 2000 and 2022. CiteSpace software was imported for visualization analysis of countries, institutions, co-cited authors and co-cited journals and sorting of high-frequency keywords, as well as co-cited references and keyword co-occurrence, clustering and bursting display. Results: A total of 594 publications on neuroendocrine tumours of the lung were available, from 2000 to 2022, with an overall upward trend of annual publications in the literature. Authors or institutions from the United States, Italy, Japan and China were more active in this field, but there was little cooperation among the major countries. Co-cited references and keyword co-occurrence and cluster analysis showed that research on diagnostic instruments, pathogenesis, ectopic ACTH signs, staging and prognosis and treatment was a current research hotspot. The keyword bursts suggested that therapeutic approaches might be a key focus of future research into the field for pulmonary neuroendocrine tumors. Conclusion: Over these 20 years, research related to neuroendocrine tumors of the lung has increased in fervour, with research on diagnostic instruments, pathogenesis, ectopic ACTH signs, staging and prognosis, and treatment being the main focus of research. Therapeutic treatments may be the future research trend in this field.

M1 linear ubiquitination of LKB1 inhibits vascular endothelial cell injury in atherosclerosis through activation of AMPK.

Endothelial cell injury is confirmed to be the initial step in the atherosclerosis (AS) process. Here, we tried to elucidate the role of liver kinase B1 (LKB1) and adenosine phosphate protein kinase (AMPK) in modulating vascular endothelial cells (VECs) in AS. High-fat feed (HFD)-induced AS rat models were prepared and treated with AMPK activator A-769662 alone or combined with chloroquine. An analysis of VEC injury, inflammation response, and autophagy followed it. The M1 linear ubiquitination of LKB1 was assessed by co-immunoprecipitation. The interaction between LKB1 and AMPK was analyzed. Primary aortic VECs were isolated and induced by LPS to verify the effects of LKB1 and AMPK on VEC injury in AS. Activation of AMPK reduced the VEC injury and inflammatory response of VECs and promoted autophagy caused by AS. LKB1 could regulate the activation of AMPK in AS. M1 linear ubiquitination enhanced LKB1 activity and increased AMPK activation to protect against VEC injury in AS, which was validated by in vitro experiments. Our current study highlighted that M1 linear ubiquitination of LKB1 may induce the activation of LKB1 to activate AMPK, which inhibited VEC injury in AS.

Engineered lytic phage of Bacillus cereus and its application in milk.

Phages have been approved for use in the food industry to control bacterial contamination in some countries. However, their broader adoption is hindered by some limitations. For instance, the persistence of infectious phages in the food industry can lead to the emergence of resistant bacteria, which negatively impacts the long-term effectiveness of phages. Additionally, the narrow host range of phages limits their effectiveness against various strains. To address these deficiencies, phage engineering has been proposed as a rational approach for modifying phages. In this study, we developed a simple and efficient engineering method for Bacillus cereus phage, using DK1 as an example, to reduce the number of residual phages and expand its range of hosts. Specifically, we knocked out the appendage gene, which codes for the receptor-binding protein, to produce phage progeny with structural defects in their appendages, resulting in the loss of infectivity after host elimination. Furthermore, we used plasmid-mediated means to express different appendage proteins during phage preparation, which allowed altering the host spectrum of the engineered phages without gene insertion. In practical applications, our engineered phages effectively reduced the number of B. cereus in milk and prevented the amplification of active progeny. Our strategy transformed phages from active viruses into more controllable antibacterial agents, making them safer and more efficient for the prevention and control of B. cereus. Moreover, we believe this strategy will help drive the use of engineered phages in the food industry.

[Establishment and evaluation of rabbit model of closed tibial fracture].

OBJECTIVE: To explore the effect of a modified three-point bending fracture device for establishing a rabbit model of closed tibial fracture. METHODS: The model of closed tibial fracture was established in 40 6-month-old male New Zealand white rabbits with a body weight of 2.5 to 3.0 kg, and the model was verified at 6 weeks after operation. Five rabbits underwent pre modeling without temporary external fixation before modeling, and then were fractured with a modified three-point bending fracture device;35 rabbits underwent formal modeling. Before modeling, needles were inserted, and splints were fixed externally, and then the fracture was performed with a modified three-point bending fracture device. The fracture model and healing process were evaluated by imaging and histopathology at 2 hours, 4 weeks, and 6 weeks after operation. RESULTS: Two hours after modeling, the prefabricated module showed oblique fracture in varying degrees and the broken end shifted significantly;Except for 1 comminuted fracture, 2 curved butterfly fractures and 2 without obvious fracture line, the rest were simple transverse and oblique fractures without obvious displacement in formal modeling group. According to the judgment criteria, the success rate of the model was 85.71%. Four weeks after modeling, the fixed needle and splint of the experimental rabbits were in good position, the fracture alignment was good, the fracture line was blurred, many continuous callus growths could be seen around the fracture end, and the callus density was high. Six weeks after modeling, many thick new bone trabeculae at the fracture, marginal osteoblasts attached, and a small number of macrophages were seen under the microscope. The intramembrane osteogenesis area was in the preparation bone stage, the medullary cavity at the fracture had been partially reopened, the callus was in the absorption plastic stage, and many osteoclasts were visible. The X-ray showed that the fracture line almost disappeared, part of the medullary cavity had been opened, the external callus was reduced around, the callus was in the plastic stage, and the bone cortex was continuous. It suggests that the fracture model showed secondary healing. CONCLUSION: The improved three-point bending fracture device can establish a stable rabbit model of closed tibial fracture, and the operation is simple, which meets the requirements of closed fracture model in basic research related to fracture healing.

Experimental and Numerical Analysis of Stitched Composite Laminates Subjected to Low-Velocity Edge-on Impact and Compression after Edge-on Impact.

Composite laminates are susceptible to impact events during use and maintenance, affecting their safety performance. Edge-on impact is a more significant threat to laminates than central impact. In this work, the edge-on impact damage mechanism and residual strength in compression were investigated using experimental and simulation methods by considering variations in impact energy, stitching, and stitching density. The damage to the composite laminate after edge-on impact was detected in the test by visual inspection, electron microscopic observation, and X-ray computed tomography techniques. The fiber and matrix damage were determined according to the Hashin stress criterion, while the cohesive element was used to simulate the interlaminar damage. An improved Camanho nonlinear stiffness discount was proposed to describe the stiffness degradation of the material. The numerical prediction results matched well with the experimental values. The findings show that the stitching technique could improve the damage tolerance and residual strength of the laminate. It can also effectively inhibit crack expansion, and the effect increases with increasing suture density.

Controlled self-cleaning aluminum surfaces mediated by anodic aluminum oxide.

Special porous anodic aluminum oxide (AAO) membranes are created on Al in a phosphonic acid electrolyte solution through one-step anodic oxidation and modified with polydimethysiloxane using a vapor deposition technique. In this context, the anodic oxidation time is tuned during its process. As such, the Al surface's wettability, and self-cleaning property are controlled by the tunable anodic oxidation time, for the anodic oxidation, time can regulate the structure of the AAO and the proportion of the air-liquid interface.

Recent advances in phage defense systems and potential overcoming strategies.

Bacteriophages are effective in the prevention and control of bacteria, and many phage products have been permitted and applied in the field. Because bacteriophages are expected to replace other antimicrobial agents like antibiotics, the antibacterial effect of bacteriophage has attracted widespread attention. Recently, the diversified defense systems discovered in the target host have become potential threats to the continued effective application of phages. Therefore, a systematic summary and in-depth illustration of the interaction between phages and bacteria is conducive to the development of this biological control approach. In this review, we introduce different defense systems in bacteria against phages and emphasize newly discovered defense mechanisms in recent years. Additionally, we draw attention to the striking resemblance between defense system genes and antibiotic resistance genes, which raises concerns about the potential transfer of phage defense systems within bacterial populations and its future impact on phage efficacy. Thus, attention should be given to the effects of phage defense genes in practical applications. This article is not exhaustive, but strategies to overcome phage defense systems are also discussed to further promote more efficient use of phages.

Eosinophil: A New Circulating Biomarker for Risk of Poor Outcome in Stroke Patients Undergoing Mechanical Thrombectomy.

Objective: Acute ischemic stroke (AIS), caused by occlusion of large vessel, is a serious life-threatening disease. This study aimed to comprehensively investigate the association of 14 common and readily available circulating biomarkers with the 90-day modified Rankin Scale (mRS) score in patients undergoing mechanical thrombectomy (MT). Methods: This study included patients with anterior circulation large vessel occlusive stroke treated with MT from 05/2017 to 12/2021. Baseline comparisons of poor outcome were performed among enrolled patients. Factors that may be associated with the mRS score were assessed using correlation analysis. Univariate and multivariate logistic regression analyses were used to evaluate the predictive value of circulating biomarkers and poor outcome. Results: The mRS score has a strong correlation with neutrophil to lymphocyte ratio (NLR) and eosinophil levels (all rs>0.4 in absolute value and all P<0.001) in addition to a high correlation with National Institute of Health Stroke Scale (NIHSS) score (rs=0.40, P<0.001). There was also a high correlation between NLR and eosinophil (rs=-0.58, P<0.001). In the multivariate regression analysis, only neutrophil (adjusted OR=1.301, 95% CI: 1.155-1.465, P<0.001), eosinophil (adjusted OR<0.001, 95% CI: <0.001-0.016, P<0.001), and NLR (adjusted OR=1.158, 95% CI: 1.082-1.241, P<0.001) were independently associated with poor outcome. Conclusion: This study evaluated a series of circulating biomarkers and found that neutrophil, eosinophil, and NLR independently predicted poor outcome after MT in AIS patients. There was a significant negative correlation between eosinophil and NLR levels.

Euchromatic histone lysine methyltransferase 2 facilitates radioresistance in prostate cancer by repressing endoplasmic reticulum protein 29 transcription.

Prostate cancer is one of the most common cancers in men. This study was conducted to investigate the role of euchromatic histone lysine methyltransferase 2 (EHMT2) and endoplasmic reticulum protein 29 (ERP29) in the progression of radioresistance in prostate cancer. The expression of EHMT2 and ERP29 in prostate cancer cells and during the progression of radioresistance was detected using quantitative reverse transcription-polymerase chain reaction and western blotting, and the interaction between EHMT2 and ERP29 was investigated. The proliferation of transfected cells under x-ray irradiation was determined using the methyl thiazolyl tetrazolium and colony formation assays. Flow cytometry was used to analyze the apoptosis of the transfected cells under x-ray irradiation. Nude mice were subcutaneously injected with prostate cancer (DU145) cells stably transfected with sh-ERP29 or sh-NC. The effect of ERP29 expression on radioresistance in nude mice was assessed by x-ray irradiation. The expression of EHMT2 was upregulated and that of ERP29 was downregulated in prostate cancer cells during radioresistance progression. EHMT2 downregulation suppressed radioresistance in DU145 and androgen-sensitive prostate cancer (LNCaP) cells. In irradiated DU145 cells, EHMT2 inhibition decreased the number of colonies and accelerated apoptosis. The transcription of ERP29 was suppressed by EHMT2 by upregulating H3K9me2 and downregulating H3K4me3, thereby regulating radioresistance in prostate cancer cells. In addition, the downregulation of ERP29 promoted the progression of radioresistance in prostate cancer cells in nude mice. EHMT2 promotes radioresistance in prostate cancer cells by repressing ERP29 transcription.

Exploration of the anti-hyperuricemia effect of TongFengTangSan (TFTS) by UPLC-Q-TOF/MS-based non-targeted metabonomics.

BACKGROUND: TongFengTangSan (TFTS) is a commonly used Tibetan prescription for gout treatment. Previously, TFTS (CF) was confirmed to have a significant uric acid-lowering effect. However, the anti-hyperuricemia mechanisms and the main active fractions remain unclear. The current study aimed to investigate the anti-hyperuricemia mechanism using metabolomics and confirm the active CF fraction. METHODS: The hyperuricemia model was established through intraperitoneal injection containing 100 mg/kg potassium oxonate and 150 mg/kg hypoxanthine by gavage. We used serum uric acid (sUA), creatinine (CRE), blood urea nitrogen (BUN), xanthine oxidase (XOD) activity, interleukin-6 (IL-6) and interleukin-1ß (IL-1ß) as indicators to evaluate the efficacy of CF and the four fractions (SX, CF30, CF60, and CF90). The anti-hyperuricemia mechanism of CF was considered through non-targeted metabolomics depending on the UPLC-Q-TOF-MS technology. Principle component analysis (PCA) and orthogonal partial least squares-discriminant analysis (OPLS-DA) helped explore the potential biomarkers in hyperuricemia. Moreover, the differential metabolites and metabolic pathways regulated by CF and four fractions were also assessed. RESULTS: CF revealed a significant anti-hyperuricemia effect by down-regulating the level of sUA, sCRE, sIL-1ß, and XOD. SX, CF30, CF60, and CF90 differed in the anti-hyperuricemia effect. Only CF60 significantly lowered the sUA level among the four fractions, and it could be the main efficacy fraction of TFTS. Forty-three differential metabolites were identified in hyperuricemia rats from plasma and kidney. Pathway analysis demonstrated that seven pathways were disrupted among hyperuricemia rats. CF reversed 19 metabolites in hyperuricemia rats and exerted an anti-hyperuricemia effect by regulating purine metabolism. CF60 was the main active fraction of TFTS and exerted a similar effect of CF by regulating purine metabolism. CONCLUSIONS: CF and CF60 could exert an anti-hyperuricemia effect by regulating the abnormal purine metabolism because of hyperuricemia while improving intestinal and renal function. CF60 could be the main active fraction of TFTS.

Effects of Different Etiologies of Anterior Circulation Tandem Lesions on Short-term Prognosis of Acute Ischemic Stroke.

INTRODUCTION: The prognosis of anterior circulation tandem lesions caused by carotid artery dissection (CAD) and large artery atherosclerosis (LAA) after mechanical thrombectomy is controversial. By analyzing the clinical data of different etiologies, we explored the best treatment plan. METHODS: Clinical data of patients with anterior circulation tandem lesions admitted to the Second Affiliated Hospital of Soochow University from April 2018 to October 2021 were retrospectively collected. The Modified Rankin Scale was used as the standard to evaluate the functional prognosis of patients at 3 months. Safety assessment included symptomatic intracranial hemorrhage (sICH) and mortality. The technical evaluation of interventional procedures included operation time, successful recanalization, and times of pass. RESULTS: 74 patients were enrolled, 59 in the LAA group and 15 in the CAD group. The two groups were similar regarding the proportion of successful recanalization, the bridge treatment and the choice of surgical instruments. The puncture to recanalization time and the onset of symptoms to successful recanalization time had no significant difference (p > 0.05). There were no significant differences in hemorrhage transformation (p = 0.26), sICH (p > 0.999), good functional prognosis (p = 0.054), and mortality (p = 0.181) between the two groups. We found a trend toward a better functional outcome at 3 months in the CAD group (p = 0.054). CONCLUSION: The tandem lesions of anterior circulation caused by CAD tend to have a good functional prognosis in 3 months. The proportion of successful recanalization and surgical safety was similar between the two groups.