Neuroimaging Marker-CT Perfusion of Early Neurological Deterioration in Patients with Minor Stroke and Large Vessel Occlusion after Intravenous Thrombolysis.

OBJECTIVE: Early Neurological Deterioration (END) is one of the complications in Acute ischemic stroke (AIS) and relates to prognosis. However, the reason why it occurs is still unclear. Our study is to investigate if CT perfusion (CTP) can predict END in patients with Minor Stroke and Large Vessel Occlusion after Intravenous Thrombolysis (IVT). METHODS: Patients who underwent IVT with Large Vessel Occlusion were enrolled continuously from January 2021 to August 2023. After evaluating the National Institutes of Health Stroke Scale (NIHSS) score, they were divided into the END group (n=21) and the Non-END group (n=20). Multivariate logistic regression analysis was performed to explore the factors of END. Receiver-operating characteristic (ROC) curve analysis was also used to assess the discriminative ability of CTP in predicting END. RESULTS: A total of 41 patients (mean age, 62.34 ± 10.82 years, 27 male) were finally included in the analysis; 21 patients had END, and 9 patients underwent Endovascular thrombectomy (EVT). Multivariate logistic regression analysis indicated that rCBV (OR=0.081, 95%CI=0.009- 0.721, p = 0.024) and admission-NIHSS (OR=1.990, 95%CI=1.049-3.772, p = 0.035) were significantly associated with END. The area under the curve (AUC) of rCBV and NIHSS to discriminate END were 0.708 and 0.758. We found patients with END had a higher modified Rankin Scale (mRS) in 3 months. CONCLUSIONS: The rCBV and NIHSS were associated with post-thrombolysis END and may become reliable markers to predicate END. END might predict a poor 3-month functional outcome.

An interpretable machine learning model for stroke recurrence in patients with symptomatic intracranial atherosclerotic arterial stenosis.

Background and objective: Symptomatic intracranial atherosclerotic stenosis (SICAS) is the most common etiology of ischemic stroke and one of the main causes of high stroke recurrence. The recurrence of stroke is closely related to the prognosis of ischemic stroke. This study aims to develop a machine learning model based on high-resolution vessel wall imaging (HR-VWI) to predict the risk of stroke recurrence in SICAS. Methods: This study retrospectively collected data from 180 SICAS stroke patients treated at the hospital between 2020.01 and 2022.01. Relevant imaging and clinical data were collected, and follow-up was conducted. The dataset was divided into a training set and a validation set in a ratio of 7:3. We employed the least absolute shrinkage and selection operator (LASSO) regression to perform a selection on the baseline data, laboratory tests, and neuroimaging data generated by HR-VWI scans collected from the training set. Finally, five machine learning techniques, including logistic regression model (LR), support vector machine (SVM), Gaussian naive Bayes (GNB), Complement naive Bayes (CNB), and k-nearest neighbors algorithm (kNN), were employed to develop a predictive model for stroke recurrence. Shapley Additive Explanation (SHAP) was used to provide visualization and interpretation for each patient. The model's effectiveness was evaluated using average accuracy, sensitivity, specificity, precision, f1 score, PR curve, calibration curve, and decision curve analysis. Results: LASSO analysis revealed that "history of hypertension," "homocysteine level," "NWI value," "stenosis rate," "intracranial hemorrhage," "positive remodeling," and "enhancement grade" were independent risk factors for stroke recurrence in SICAS patients. In 10-fold cross-validation, the area under the curve (AUC) ranged from 0.813 to 0.912 in ROC curve analysis. The area under the precision-recall curve (AUPRC) ranged from 0.655 to 0.833, with the Gaussian Naive Bayes (GNB) model exhibiting the best ability to predict stroke recurrence in SICAS. SHAP analysis provided interpretability for the machine learning model and revealed essential factors related to the risk of stroke recurrence in SICAS. Conclusion: A precise machine learning-based prediction model for stroke recurrence in SICAS has been established to assist clinical practitioners in making clinical decisions and implementing personalized treatment measures.

An integrative analysis of single-cell and bulk transcriptome and bidirectional mendelian randomization analysis identified C1Q as a novel stimulated risk gene for Atherosclerosis.

Background: The role of complement component 1q (C1Q) related genes on human atherosclerotic plaques (HAP) is less known. Our aim is to establish C1Q associated hub genes using single-cell RNA sequencing (scRNA-seq) and bulk RNA analysis to diagnose and predict HAP patients more effectively and investigate the association between C1Q and HAP (ischemic stroke) using bidirectional Mendelian randomization (MR) analysis. Methods: HAP scRNA-seq and bulk-RNA data were download from the Gene Expression Omnibus (GEO) database. The C1Q-related hub genes was screened using the GBM, LASSO and XGBoost algorithms. We built machine learning models to diagnose and distinguish between types of atherosclerosis using generalized linear models and receiver operating characteristics (ROC) analyses. Further, we scored the HALLMARK_COMPLEMENT signaling pathway using ssGSEA and confirmed hub gene expression through qRT-PCR in RAW264.7 macrophages and apoE-/- mice. Furthermore, the risk association between C1Q and HAP was assessed through bidirectional MR analysis, with C1Q as exposure and ischemic stroke (IS, large artery atherosclerosis) as outcomes. Inverse variance weighting (IVW) was used as the main method. Results: We utilized scRNA-seq dataset (GSE159677) to identify 24 cell clusters and 12 cell types, and revealed seven C1Q associated DEGs in both the scRNA-seq and GEO datasets. We then used GBM, LASSO and XGBoost to select C1QA and C1QC from the seven DEGs. Our findings indicated that both training and validation cohorts had satisfactory diagnostic accuracy for identifying patients with HPAs. Additionally, we confirmed SPI1 as a potential TF responsible for regulating the two hub genes in HAP. Our analysis further revealed that the HALLMARK_COMPLEMENT signaling pathway was correlated and activated with C1QA and C1QC. We confirmed high expression levels of C1QA, C1QC and SPI1 in ox-LDL-treated RAW264.7 macrophages and apoE-/- mice using qPCR. The results of MR indicated that there was a positive association between the genetic risk of C1Q and IS, as evidenced by an odds ratio (OR) of 1.118 (95%CI: 1.013-1.234, P = 0.027). Conclusion: The authors have effectively developed and validated a novel diagnostic signature comprising two genes for HAP, while MR analysis has provided evidence supporting a favorable association of C1Q on IS.

Comparative analysis of 3D time-resolved contrast-enhanced magnetic resonance angiography, color Doppler ultrasound and digital subtraction angiography in symptomatic carotid stenosis.

The present study aimed to compare the diagnostic value of contrast-enhanced magnetic resonance angiography (CE MRA) with 3D time-resolved imaging of contrast kinetics, color Doppler ultrasound (CDUS) and digital subtraction angiography (DSA) in extracranial carotid stenosis (CS). A total of 54 patients with symptomatic CS were subjected to CDUS, CE MRA and DSA examination. Results of DSA were defined as the standard, and a total of 216 vessels were examined. In each patient four vessels were examined, namely the bilateral common carotid arteries and the bilateral internal carotid arteries. The sensitivities and specificities of CE MRA and CDUS for various degrees of CS were also determined. It was observed that the sensitivities to mild-level (1-49%), moderate-level (50-69%) and severe-level (70-99%) CS were 85.45, 100 and 100% for CE MRA, and 78.18, 50 and 100% for CDUS, respectively. The corresponding specificities were 95.27, 98.58 and 99.53% for CE MRA, and 79.05, 93.36 and 98.10% for CDUS, respectively. In addition, the carotid sinus plaque detection rate for CDUS was significantly higher than that of DSA and CE MRA (both P<0.001). Detection rates for common carotid artery plaques and internal carotid artery plaques did not significantly differ among the three examination methods (all P>0.05). These data demonstrate that CE MRA has higher sensitivity and specificity than CDUS for the diagnosis of CS, and that CDUS has a higher carotid sinus plaque detection rate than DSA and CE MRA. Therefore, the combination of MRI and CDUS may be a 'gold standard' diagnostic method for the detection of moderate and severe CS.

A comparison of contrast-free MRA at 3.0T in cases of intracranial aneurysms with or without subarachnoid hemorrhage.

PURPOSE: To determine the diagnostic accuracy of contrast-free MRA at 3.0T for detection of intracranial aneurysms in patients with subarachnoid hemorrhage. METHODS: 411 patients (183 with SAH and 228 with non-SAH) underwent MRA. Accuracy, sensitivity, specificity, positive predictive values (PPV), and negative predictive values (NPV) were measured and compared with DSA. RESULTS: Except for a slight difference in sensitivity in patient-based and aneurysm-based evaluations (P=0.037), there were no other significant differences in accuracy, specificity, PPV, and NPV. CONCLUSION: VR 3D-TOF-MRA is a non-invasive approach with high accuracy in the diagnosis of intracranial aneurysms.

Intermediate analysis of magnesium alloy covered stent for a lateral aneurysm model in the rabbit common carotid artery.

OBJECTIVE: To analyze the outcomes of a magnesium alloy covered stent (MACS) for a lateral aneurysm model in common carotid artery (CCA). METHODS: In 32 rabbits, a MACS (group A, n = 17) or a Willis covered stent (WCS; group B, n = 15) was inserted and the rabbits were sacrificed 1, 3, 6, or 12 months after stenting. Angiography and intravascular ultrasound (IVUS) were performed at 3, 6, and 12 months. Scanning electron microscopy was performed for six stents in each group at 1, 3, and 6 months, and histopathology and histomorphology were conducted at 3 (n = 4), 6 (n = 4), and 12 (n = 12) months. RESULTS: Final angiography showed complete occlusion of the aneurysms in 12 cases. IVUS at 6 and 12 months revealed a significant increase in mean lumen area of the stented CCA in group A and also showed greater mean lumen area in group A than in group B. The endothelialization process was quicker in group A than in group B. CONCLUSION: MACS is effective for occlusion of lateral aneurysms and is superior to WCS in growth of the stented CCA and endothelialization. Further work is needed to make this device available for human use. KEY POINTS: • The MACS is an effective approach for occlusion of a lateral aneurysm. • IVUS showed that the CCA could grow following degradation of the MACS. • The lumen area of the stented CCA was excellent in MACS. • HE staining displayed the degradation of the magnesium alloy stent. • Combination of IVUS and DSA were applied in this study.

Comparative analysis between 64- and 320-slice spiral computed tomography in the display of coronary artery stents and diagnosis of in-stent restenosis.

The aim of the present study was to compare the accuracy of 64-multi-slice spiral computed tomography (64-MSCT) and 320-MSCT in the display of coronary artery stents and diagnosis of in-stent restenosis. The data collected from the 64- and 320-MSCT coronary angiography of 93 patients following coronary artery stent implantation were retrospectively analyzed. The 64-MSCT group comprised 30 cases with 57 stents and the 320-MSCT group comprised 63 cases with 93 stents. The image quality, heart rate of the patients and the radiation effective dose (ED) they were subjected to, were compared. Furthermore, the diagnostic abilities of 64-and 320-MSCT coronary angiography for in-stent restenosis were evaluated using invasive coronary angiography results as the gold standards. Statistically significant differences were observed in the heart rate and ED of the patients from the two groups (P<0.05), but no significant difference was identified in the accuracy index (P>0.05). The sensitivity, specificity, positive and negative predictive value and accuracy of the 64-MSCT group were found to be 100% (7/7), 93.94% (31/33), 77.78% (7/9), 100% (31/31) and 95% (38/40), respectively, and those in the 320-MSCT group were found to be 100% (16/16), 95.89% (70/73), 84.21% (16/19), 100% (70/70) and 96.63% (86/89), respectively. The present findings suggest that both 64-MSCT and 320-MSCT can be used for follow-up and curative effect evaluation following coronary stent implantation; however, 320-MSCT has fewer requirements of the patients' heart rate and uses a lower radiation dose.

Down-regulation of Rab17 promotes tumourigenic properties of hepatocellular carcinoma cells via Erk pathway.

The small GTPase, Ras-related protein 17 (Rab17), a member of the Rab family, plays a critical role in the regulation of membrane traffic in polarized eukaryotic cells. However, the role of Rab17 in hepatocellular carcinoma (HCC) is not clear. Clinical speciments reveal that Rab17 was present in 15 of 20 (75.0%) paraneoplastic tissues and 7 of 20 (35.0%) HCC samples (P=0.0248). To elucidate the tumourigenic role of Rab17 in HCC, we generated two Rab17 low-expressing HCC cell lines (Hep3B and Huh-7). The results showed that Rab17 down-regulation significantly promoted the tumourigenic properties of HCC cells in vitro and in vivo, as demonstrated by enhanced cell proliferation, colony formation, invasion and migration, decreased G1 arrest, and increased tumour xenograft growth and angiogenesis. However, the enhanced tumourigenic properties of HCC cells by Rab17 down-regulation was significantly inhibited by PD980592, the inhibitor of the Erk pathway, indicating that the Erk pathway plays a critical role in Rab17 down-regulation-induced enhanced tumourigenic properties of HCC cells. Our data provide a new insight into the essential role of Rab17 in HCC carcinogenesis and suggest that Rab17 expression might be tumor suppressor gene and might provide a new interventional therapeutic target for this common malignancy.

MicroRNA-194 acts as a prognostic marker and inhibits proliferation in hepatocellular carcinoma by targeting MAP4K4.

MicroRNAs (miRNAs) play a crucial role in cancer development and progression of hepatocellular carcinoma (HCC). In this study, we aimed to analyze the role of microRNA-194 (miR-194) in HCC. We found that miR-194 expression was significantly reduced in HCC and its expression was an independent poor prognostic factor for HCC patient overall and disease-free survival rate. A significant correlation was observed between miR-194 reduction and unfavourable variables including tumor size (P = 0.0315), histologic grade (P = 0.0038), TNM stage (P = 0.0083), intrahepatic metastasis (P = 0.0184). Overexpression of miR-194 in HCC cell lines HepG2 and Hep3B inhibited cell proliferation by blocking G1-S transition and inducing apoptosis. Mitogen-activated protein kinase 4 (MAP4K4), a potential target gene of miR-194, was inversely correlated with miR-194 expression in HCC tissues and cell lines. Further studies demonstrated that miR-194 regulated the progression of HCC through directly inhibiting the expression of MAP4K4 and the restoration of MAP4K4 expression reversed the inhibitory effects of miR-194 on HCC cell proliferation. Together, our findings indicate that miR-194 may serve as a valuable prognostic marker and promising interventional therapeutic target for HCC.

Platelet-derived growth factor-ß expression in rabbit models of cerebral vasospasm following subarachnoid hemorrhage.

Subarachnoid hemorrhage (SAH), one of the serious types of stroke incurred by bleeding into the space surrounding the brain, occurs when brains are deprived of oxygen by various factors, particularly an interruption to the blood supply or a ruptured aneurysm. Cerebral vasospasm (CVS) is one of the most common complications of SAH. It has been proposed that platelet­derived growth factor (PDGF) is involved in CVS. The aim of the present study was to analyze expression of PDGF in rabbit models of CVS. Post-SAH CVS rabbit models were created using endovascular puncture and employed to analyze the expression patterns of PDGF by enzyme-linked immunosorbent assay and immunohistochemistry. The results indicated that the creation of the rabbit model of CVS induced using endovascular puncture was successful and demonstrated the double phase changes observed in human CVS. The acute stage started at 12 h post-SAH with narrowing of the vascular lumen diameter. This narrowing appeared again on the seventh day in delayed CVS alongside increased thickness of vessel walls. PDGF-ß expression was observed in vascular smooth muscle cells of the rabbit models. PDGF-ß was expressed as early as 3 h post-SAH, it was evident after 1 day and reached a peak in 7 days, suggesting that PDGF-ß is involved in the early stages of CVS. In the current study, it was confirmed that PDGF-ß expression was present in the rabbit models of CVS, which may aid the elucidation of the pathogenesis of CVS, and also provide useful information for diagnosis and treatment of CVS.

Clinical features and magnetic resonance image analysis of 15 cases of demyelinating leukoencephalopathy induced by levamisole.

The aim of this study was to explore the diagnostic value of magnetic resonance imaging (MRI) for levamisole-induced demyelinating leukoencephalopathy. The clinical features and MRI findings of 15 patients with levamisole-induced demyelinating leukoencephalopathy were retrospectively analyzed. The abnormality rate of the patients was demonstrated to be 100% by MRI, and scattered multiple cerebral foci were observed in all of the patients. The majority of the foci were located at the centrum ovale, peri-lateral cerebral ventricles and basal ganglia, while the remainder were located in the brain stem and cerebellum, as well as in the white matter regions of the temporal, frontal, apical and occipital lobes. In addition, mottling and ring-shaped enhancements were observed. The study demonstrated that MRI effectively displays demyelinating leukoencephalopathy, and that the combination of MRI with the medical history of the patient is of significance for the early diagnosis, differentiation and treatment of demyelinating leukoencephalopathy.

Synergistic antitumor activity of reversine combined with aspirin in cervical carcinoma in vitro and in vivo.

A recent report showed that reversine treatment could induce murine myoblasts dedifferentiation into multipotent progenitor cells and inhibit proliferation of some tumors, and other reports showed that apoptosis of lung adenocarcinoma cells could be induced by aspirin. The aim of the present study was to evaluate the synergistic antitumor effects of reversine and aspirin on cervical cancer. The inhibition rate of reversine and aspirin on cervical cancer cell lines' (HeLa and U14) was determined by MTT method, cell cycle of HeLa and U14 cells was analyzed by FACS, mitochondrial membrane potential of HeLa and U14 was detected using a JC-1 kit. HeLa and U14 colony formation was analyzed by soft agar colony formation assay. The expression of caspase-3, Bcl-2/Bax, cyclin D1 and p21 was detected by qRT-PCR and Western Blotting. Moreover, tumor weight and tumor volume was assessed using a murine model of cervical cancer with U14 cells subcutaneously (s.c.) administered into the neck, separately or combined with drug administration via the intraperitoneal (i.p.) route. The inhibition rate of cells in the combination group (10 µmol/L reversine, 10 mmol/L aspirin) increased significantly in comparison to that when the drugs were used alone (P < 0.05); moreover, this combination could synergistically inhibit the proliferation of five cervical cancer cell lines (HeLa, U14, Siha, Caski and C33A). In the therapeutic mouse model, tumor weight and tumor volume of cervical cancer bearing mice was more reduced when compared with the control agents (P < 0.05) in tumor-bearing mice. The combination of reversine and aspirin exerts synergistic growth inhibition and apoptosis induction on cervical cancers cells.

Measurement of normal patellar ligament and anterior cruciate ligament by MRI and data analysis.

The aim of this study was to obtain geometric data of in vivo patellar ligament (PL) and anterior cruciate ligament (ACL) by MRI and to analyze the correlation of the two with body weight, height and gender. A total of 157 cases with normal sagittal images of bilateral PL and ACL were enrolled. The PL and ACL lengths in the images were measured using the Radworks 5.1 application. The intraclass correlation coefficient for the data measured independently by three doctors was 0.997-1.000. In individuals aged 15-24 years, the values of PL and ACL length and the PL to ACL ratio were 43.95±4.25 mm, 38.45±4.62 mm and 1.15±1.09 in males and 42.03±0.94 mm, 36.00±1.06 mm and 1.18±0.1 in females, respectively. In individuals aged 25-64 years, the values in males were 40.99±4.45 mm, 36.06±3.74 mm and 1.14±0.09 and in females were 39.84±0.64 mm, 36.50±0.81 mm and 1.11±0.02, respectively. In individuals aged ≥65 years, the values in males were 41.43±3.08 mm, 36.62±3.44 mm and 1.15±0.09 and in females were 38.94±0.79 mm, 34.36±0.85 mm and 1.13±0.07, respectively. There was a significant difference between PL and ACL length on the same side (P<0.01). The data obtained was stable and repeatable. The present study established a database of PL and ACL length and the ratio of the two measured by MRI.

HDAC6 siRNA inhibits proliferation and induces apoptosis of HeLa cells and its related molecular mechanism.

OBJECTIVE: To investigate the effects of histone deacetylase 6 (HDAC6) siRNA on cell proliferation and cell apoptosis of the HeLa cervical carcinoma cell line and the molecular mechanisms involved. METHODS: Division was into three groups: A, the untreated group; B, the control siRNA group; and C, the HDAC6 siRNA group. Lipofectamine 2000 was used for siRNA transfection, and Western blot analysis was used to determine the protein levels. Cell proliferation and apoptosis were characterized using a CCK-8 assay and flow cytometry, respectively. RESULTS: HDAC6 protein expression in the HDAC6 siRNA-transfection group was significantly lower (P < 0.05) than in the untreated and control siRNA groups. The CCK-8 kit results demonstrated that the proliferation of HeLa cells was clearly inhibited in the HDAC6 siRNA transfection group (P < 0.05). In addition, flow cytometry revealed that the early apoptotic rate (26.0% ± 0.87%) was significantly elevated (P < 0.05) as compared with the untreated group (10.6% ± 1.19%) and control siRNA group (8.61% ± 0.98%). Furthermore, Western blot analysis indicated that bcl-2 protein expression in the HDAC6 siRNA-transfection group was down-regulated, whereas the expression of p21 and bax was up-regulated. CONCLUSION: HDAC6 plays an essential role in the occurrence and development of cervical carcinoma, and the down-regulation of HDAC6 expression may be useful molecular therapeutic method.

Diagnostic performance of magnetic resonance cholangiopancreatography in malignant obstructive jaundice.

Malignant obstructive jaundice is caused by tumors arising from the head of the pancreas and biliary tree, or seen due to secondary metastases in the porta hepatis lymph nodes. Magnetic resonance cholangiopancreatography (MRCP) is a non-invasive diagnostic technique that can be used for imaging the entire biliary tree and pancreatic duct system. The objective of this study was to evaluate the accuracy of MRCP in the diagnosis of malignant obstructive jaundice. The methods used involved comparative review of the images obtained by using magnetic resonance imaging and MRCP as well as comparison between MRCP- and pathology-based diagnoses. The accuracy of MRCP-based diagnosis of malignant obstructive jaundice was analyzed. Our data show that the positive rate of anatomical diagnosis and the detection rate of bile ducts on the proximal side of obstruction are 100%. The diagnostic accuracy of malignant obstruction was 82.9%. MRCP was found to have high diagnostic specificity for determining the location and extent of obstruction. We, therefore, concluded that MRCP had significance for clinical diagnosis of malignant obstructive jaundice. The positive rate of localization diagnosis was 100%. Distinguishing the quality of obstruction was also important. The diagnostic accuracy of MRCP for malignant obstructive jaundice was remarkably higher.