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Background and Purpose: Spontaneous intracranial hemorrhage (ICH) patients are still at risk of postoperative ischemic complications (PICs) after surgery. In addition, the proportion of patients receiving antiplatelet therapy (APT) in ICH patients increased significantly with age. This study aims to evaluate the impact of preoperative antiplatelet therapy on PICs in ICH patients., Methods: This is a cohort study that retrospectively analyzed the data of ICH patients who underwent surgical treatment. PICs rate was compared between patients with preoperative ATP and those without preoperative ATP. Univariate and multivariate analyses were conducted to evaluate the impact of preoperative APT on PICs. In addition, Kaplan-Meier method was used for survival analysis and the impact of PICs on patients' postoperative outcomes was evaluated., Results: A total of 216 patients were included in this study. There were 47 patients (21.76%) with preoperative APT; 169 patients (78.24%) without preoperative APT. The incidence of PICs in the APT group was significantly higher when compared with that in the nAPT group (36.17% vs. 20.71%, p  = 0.028＜0.05). Furthermore, significant differences were both observed in multivariate analysis ( p  = 0.035＜0.05) and survival analysis (log rank χ2 = 5.415, p  = 0.020＜0.05). However, there was no significant difference between the outcomes of patients suffering from PICs and that of patients not suffering from PICs ( p  = 0.377 > 0.05)., Conclusions: In conclusion, preoperative APT may be a risk factor for PICs in ICH patients undergoing surgical treatment significantly.

Background: Gastric cancer (GC) is the fifth most common malignant tumor, and it is usually fatal. Adenocarcinoma of the esophagogastric junction (AEG) accounts for about 50% of all GC cases. However, the systematic co-expression analysis of this tumor does not fully explain its pathogenesis. This study aimed to identify hub genes based on weighted gene co-expression networks and immunohistochemistry analyses., Methods: The RNA-seq data of 22 AEG patients were processed using weighted gene co-expression network analysis. We differentiated the modules with clinical tumor markers and performed Gene Ontology and pathway enrichment analysis. We identified the hub genes related to the biological processes of tumorigenesis based on weighted gene co-expression network analysis and immunohistochemistry analysis., Results: Twenty-five distinct co-expression gene modules were identified; the tumorigenic genes CD93, TRIM28, SLC3A2, CBX4, PATL1, and ZNF473 had high intramodular connectivity. Immunohistochemistry confirmed that these hub genes are upregulated in AEG. Statistical analysis indicated that the expression of CD93 was correlated with the T stage and maximum tumor diameter., Conclusion: Weighted gene co-expression network analysis and immunohistochemistry identified CD93 as a hub gene that might be critical for AEG biology., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Inc.)

Objective: Existing evidence suggests that chronic inflammation promotes the progression of human intracranial aneurysm (IA) and many cytokines have been detected to participate in the process of inflammation. However, rare cytokines in plasma have been used as proxies for progression of IA. This study aimed to identify novel cytokines as biomarkers to predict the development of IA., Methods: Patients with unruptured intracranial aneurysms (UIAs) undergoing microsurgical clipping were prospectively recruited from January 2017 to June 2020 and were separated into two groups based on their ELAPSS score (low risk group < 10, intermediate-high risk group ≥ 10). Propensity score matching (PSM) was used to reduce imbalances in the baseline characteristics between groups. All blood samples were collected before surgery. A human serum 48-cytokines examination was performed to analyze the concentrations of serological cytokines. Clinical data and cytokines were compared between groups., Results: A total of 184 patients were enrolled in this study. The low risk group contained 77 patients and 107 patients were included in the intermediate-high risk group. Finally, there were 69 patients in each group after PSM with a matching rate of 1:1. The concentrations of 3 serum cytokines were significantly increased in intermediate-high risk patients, namely, interleukin-15 (IL-15), monocyte chemoattractant protein-1 (MCP-1), and tumor necrosis factor-β (TNF-β) ( P < 0.05, |log 2 fold change| > 2). The result of receiver operator characteristic (ROC)curve revealed that TNF-β had the highest predictive accuracy, with an area under the curve (AUC) value of 0.725 [95% confidence interval (CI) 0.639-0.811, P < 0.001] followed by IL-15 (AUC = 0.691, 95% CI 0.602-0.781, P < 0.001) and MCP-1 (AUC = 0.661, 95% CI 0.569-0.753, P = 0.001). Multivariate logistic analysis demonstrated high IL-15 [odds ratio (OR), 3.23; 95% CI, 1.47-7.12; P = 0.004] and high TNF-β (OR, 8.30; 95% CI, 3.25-21.25; P < 0.001) as the risk factors that correlated with intermediate-high risk of IA progression., Conclusion: UIA patients with intermediate-high growth risk exhibited increased serum levels of IL-15, MCP-1, and TNF-β. Serum IL-15, and TNF-β could serve as biomarkers to predict the progression of UIAs., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer YW declared a shared parent affiliation with the authors to the handling editor at the time of review., (Copyright © 2022 Yang, Liu, Yang, Wu and Wang.)

Hematoma growth (HG) affects the prognosis of patients with spontaneous intracranial hematoma (ICH), but there is still a lack of evidence about the effects of aspirin (acetylsalicylic acid, ASA) on HG in patients with severe ICH. This study retrospectively analyzed patients with severe ICH who met the inclusion and exclusion criteria in Beijing Tiantan Hospital, Capital Medical University, between January 1, 2015, and July 31, 2019. Severe ICH patients were divided into ASA group and nASA groups according to ASA usage, and the incidence of HG between the groups was compared. Univariate analysis was performed by the Mann-Whitney U test, chi-square test, or Fisher exact test. Multivariate logistic regression analysis was used to analyze the impact of ASA on HG and to screen for risk factors of HG. In total, 221 patients with severe ICH were consecutively enrolled in this study. There were 72 (32.6%) patients in the ASA group and 149 patients in the nASA group. Although the incidence of HG in the nASA group was higher than that in the ASA group (34.9% VS 22.2%, p = 0.056), ASA did not significantly affect the occurrence of HG (p = 0.285) after adjusting for initial hematoma volume, high blood pressure at admission, coronary heart disease, and GCS at admission. In addition, we found that high blood pressure at admission was a risk factor for HG. Prior ASA does not increase the incidence of HG in severe ICH patients, and high blood pressure at admission is a risk factor for HG., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The 30-day mortality rate of spontaneous cerebral hemorrhage (ICH) is approximately 30-50%. Surgery may improve the prognosis of patients with severe ICH. However, ICH survivors after surgery still face the risks of postoperative intracranial rebleeding (PIB), and clinical tools that accurately predict the risk of PIB occurrence are not available. Therefore, a retrospective study was performed. The population was divided into two groups according to the occurrence of PIB. Univariate and multivariate logistic regression analyses were performed to screen risk factors for PIB. Next, an early PIB risk nomogram prediction model was constructed. In addition, the impact of PIB on the prognosis of ICH was evaluated. In total, 150 ICH patients were continuously enrolled in this study; 21 patients suffered from PIB, and the overall incidence of PIB was 14.0% (21/150). Coronary heart disease history, a lower GCS score, and subarachnoid hemorrhage absence were screened as risk factors for early PIB. The early PIB risk nomogram showed good calibration and discrimination with a concordance index of 0.807 (95% confidence interval (CI), 0.715-0.899), which was confirmed to be 0.788 through bootstrapping validation. In addition, a significant difference in discharged GOS scores (P = 0.043) was observed between the PIB group and the n-PIB group. These results showed that a history of coronary heart disease, a lower GCS score, and absence of subarachnoid hemorrhage were risk factors for early PIB. In addition, the early PIB risk nomogram prediction model exhibits good discrimination and calibration. The occurrence of PIB could reduce the prognosis of ICH patients., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: The probable stability of the lesion is critical in guiding treatment decisions in unruptured intracranial aneurysms (IAs). The authors aimed to develop multidimensional predictive models for the stability of unruptured IAs., Methods: Patients with unruptured IAs in the anterior circulation were prospectively enrolled and regularly followed up. Clinical data were collected, IA morphological features were assessed, and adjacent hemodynamic features were quantified with patient-specific computational fluid dynamics modeling. Based on multivariate logistic regression analyses, nomograms incorporating these factors were developed in a primary cohort (patients enrolled between January 2017 and February 2018) to predict aneurysm rupture or growth within 2 years. The predictive accuracies of the nomograms were compared with the population, hypertension, age, size, earlier rupture, and site (PHASES) and earlier subarachnoid hemorrhage, location, age, population, size, and shape (ELAPSS) scores and validated in the validation cohort (patients enrolled between March and October 2018)., Results: Among 231 patients with 272 unruptured IAs in the primary cohort, hypertension, aneurysm location, irregular shape, size ratio, normalized wall shear stress average, and relative resident time were independently related to the 2-year stability of unruptured IAs. The nomogram including clinical, morphological, and hemodynamic features (C+M+H nomogram) had the highest predictive accuracy (c-statistic 0.94), followed by the nomogram including clinical and morphological features (C+M nomogram; c-statistic 0.89), PHASES score (c-statistic 0.68), and ELAPSS score (c-statistic 0.58). Similarly, the C+M+H nomogram had the highest predictive accuracy (c-statistic 0.94) in the validation cohort (85 patients with 97 unruptured IAs)., Conclusions: Hemodynamics have predictive values for 2-year stability of unruptured IAs treated conservatively. Multidimensional nomograms have significantly higher predictive accuracies than conventional risk prediction scores.

Spontaneous intracranial hematoma (ICH) is the second leading cause of stroke and has a high risk of postoperative ischemic events (PIEs). But, the evidence on PIEs in ICH patients still lacks. Therefore, a retrospective study was carried out to screen the risk factors for PIEs and construct a visual predictive model. This was a retrospective study whose population were divided into two groups based on the occurrence of PIEs. Univariate logistic regression analysis was used to determine factors associated with PIEs. Multifactorial logistic regression analysis was used to screen risk factors and construct the early PIEs risk nomogram. In addition, impact of PIEs on patient prognosis and surgery related costs was assessed. Out of 122 ICH patients, 24 (19.7%) were diagnosed with PIEs. Coronary heart disease history, ischemic stroke history, regular shaped hematoma and platelet number were identified as risk factors for early PIEs. Early PIEs risk nomogram showed good calibration and discrimination of the data with concordance index of 0.846 (95% confidence interval, 0.747-0.945) which was confirmed to be 0.827 through bootstrapping validation. In addition, there was statistical difference in discharged Glasgow Coma Scale score (P = 0.046) and surgery related costs (p = 0.031) between PIEs group and nPIEs group. These results showed the early PIEs risk nomogram was accurate for prediction risks of PIEs and the occurrence of PIEs affects prognosis of patients, and increases surgery related costs., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: In order to fight against coronavirus disease 2019 (COVID-19) better and to share our experience as a reference for clinical laboratory departments., Methods: This was a retrospective study conducted in the clinical laboratory department of Chengdu Women's and Children's Central Hospital in Chengdu, China, from April 2020 to January 2021. The number of nucleic acid and antibody testing specimens of suspected COVID-19 cases was analyzed. The key points of suspected-case sample processing and detection in the clinical laboratory department were summarized. The laboratory was directly involved in the sample processing and testing of suspected cases, the release of reports, and the transfer of specimens to the fever clinic., Results: The number of COVID-19 nucleic acid test specimens in our laboratory ranged from 102 to 2170 per day, and the number of antibody test specimens ranged from 24 to 391 per day. There were four main considerations in the treatment and detection of suspected-case specimens in the clinical laboratory: biosafety management in clinical laboratory departments, measures to ensure the health of the staff, the eight time points for processing suspected-case samples (turn-around time), and key points for the detection of suspected case specimens., Conclusion: The laboratory developed a protective process for COVID-19 antibody and nucleic acid detection during the pandemic. At present, the detection of COVID-19 antibodies and nucleic acids in the clinical laboratory department is orderly, and there have been no cases of laboratory infection., Competing Interests: The authors of this manuscript have no conflicts of interest to disclose., (© 2021 Wang et al.)

Objective: To investigate the value of high-sensitivity C-reactive protein (hs-CRP) in evaluating the myocardial damage and prognosis in children with mycoplasmal pneumonia., Materials: A total of 150 children with mycoplasmal pneumonia were selected. According to their serum creatine kinase isoenzyme (CK-MB) level, they were divided into 72 cases of the myocardial damage group and 78 cases of the non-myocardial damage group. Eighty healthy children undergoing physical examination were selected as the control group. The electrocardiography results and serum CK-MB and hs-CRP levels were compared among the subjects. The correlations among the above indexes were analyzed., Results: The levels of hs-CRP and CK-MB in the myocardial damage group were significantly higher than those in the nonmyocardial damage group and control group, respectively ( P <0.05). The rates of abnormal hs-CRP and abnormal electrocardiogram in the myocardial damage group were significantly higher than those in the non-myocardial damage group, respectively ( P <0.05). In the 150 children with mycoplasmal pneumonia, the serum hs-CRP and CK-MB levels were positively correlated ( P <0.001), and the abnormal hs-CRP rate was positively correlated with the abnormal electrocardiogram rate ( P <0.001). In the myocardial damage group, the serum levels of hs-CRP and CK-MB after treatment were significantly lower than those before treatment, respectively ( P <0.05). After treatment, each index in the myocardial damage group had no significant difference with those in the control group ( P >0.05)., Conclusion: hs-CRP may be an important index for evaluating the myocardial damage and prognosis in children with mycoplasmal pneumonia. The combination of hs-CRP and CK-MB detection has obvious guiding significance for the monitoring and treatment of mycoplasmal pneumonia complicated by myocardial damage., (© 2021 by the Association of Clinical Scientists, Inc.)

Objective: Rebleeding is recognized as the main cause of mortality after intracranial aneurysm rupture. Though timely intervention can prevent poor prognosis, there is no agreement on the surgical priority and choosing medical treatment for a short period after rupture. The aim of this study was to investigate the risk factors related to the rebleeding after admission and establish predicting models for better clinical decision-making., Methods: The patients with ruptured intracranial aneurysms (RIAs) between January 2018 and September 2020 were reviewed. All patients fell to the primary and the validation cohort by January 2020. The hemodynamic parameters were determined through the computational fluid dynamics simulation. Cox regression analysis was conducted to identify the risk factors of rebleeding. Based on the independent risk factors, nomogram models were built, and their predicting accuracy was assessed by using the area under the curves (AUCs)., Result: A total of 577 patients with RIAs were enrolled in this present study, 86 patients of them were identified as undergoing rebleeding after admission. Thirteen parameters were identified as significantly different between stable and rebleeding aneurysms in the primary cohort. Cox regression analysis demonstrated that six parameters, including hypertension [hazard ratio (HR), 2.54; P = 0.044], bifurcation site (HR, 1.95; P = 0.013), irregular shape (HR, 4.22; P = 0.002), aspect ratio (HR, 12.91; P < 0.001), normalized wall shear stress average (HR, 0.16; P = 0.002), and oscillatory stress index (HR, 1.14; P < 0.001) were independent risk factors related to the rebleeding after admission. Two nomograms were established, the nomogram including clinical, morphological, and hemodynamic features (CMH nomogram) had the highest predicting accuracy (AUC, 0.92), followed by the nomogram including clinical and morphological features (CM nomogram; AUC, 0.83), ELAPSS score (AUC, 0.61), and PHASES score (AUC, 0.54). The calibration curve for the probability of rebleeding showed good agreement between prediction by nomograms and actual observation. In the validation cohort, the discrimination of the CMH nomogram was superior to the other models (AUC, 0.93 vs. 0.86, 0.71 and 0.48)., Conclusion: We presented two nomogram models, named CMH nomogram and CM nomogram, which could assist in identifying the RIAs with high risk of rebleeding., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer XY declared a shared affiliation, with no collaboration with the authors to the handling editor at the time of the review., (Copyright © 2021 Liu, Yang, Yang, Li, Yang, Wang, Wu, Jiang and Wang.)

Background: The corpus callosum (CC) plays a key role in mediating interhemispheric connectivity and developing functional hemispheric asymmetries. The purpose of this study was to investigate the changes in CC microstructure accompanying interhemispheric language reorganization in patients with brain arteriovenous malformations (AVMs). Methods: Forty-one patients with an unruptured AVM located in anatomically defined language areas underwent functional magnetic resonance imaging and diffusion tensor imaging. Hemispheric dominance in Broca's area (BA) and Wernicke's area (WA) was assessed separately. Right-sided or bilateral language dominance was classified as atypical lateralization. The CC was segmented into five subregions, and the mean fractional anisotropy (FA) was extracted. The relationship between callosal FA and language lateralization patterns was statistically analyzed. Results: We observed atypical language lateralization in 16 (39.0%) patients. Patients with atypical lateralization exhibited significantly higher mean FA values in the total CC ( p  = 0.002) and the anterior ( p  = 0.047), midanterior ( p  = 0.001), and midposterior ( p  = 0.043) subregions. Significant interaction effects of BA and WA lateralization were found for FA values in the total CC ( p  = 0.005) and the midanterior subregion ( p  = 0.004). Conclusions: These results indicate that AVM patients with atypical language lateralization exhibit higher callosal FA values, reflecting greater interhemispheric connectivity. Our findings contribute additional insights into the understanding of functional and structural plasticity of the human brain under pathological states. Impact statement Brain arteriovenous malformations (AVMs) are congenital lesions that frequently lead to interhemispheric language reorganization. In this study, by combining diffusion tensor imaging and functional magnetic resonance imaging, we investigated the relationship between callosal fractional anisotropy (FA) and language reorganization in patients with AVMs. We found that callosal FA was significantly higher in patients with atypical language lateralization, especially in those with crossed lateralization of Broca's and Wernicke's areas. This study demonstrated the remodeling of the corpus callosum microstructure accompanying language reorganization in AVM patients, providing insights into the structural and functional plasticity of the human brain associated with congenital cerebrovascular disease.

Objective: Recently, abundant number of studies have revealed many functions of circular RNAs in multiple diseases, however, the role of circular RNA in the rupture of human intracranial aneurysm is still unknown. This study aims to explore the potential functions of circular RNA in the rupture of human intracranial aneurysms. Methods: The differentially expressed circular RNAs between un-ruptured intracranial aneurysms ( n = 5) and ruptured intracranial aneurysms ( n = 5) were analyzed with the Arraystar human circRNAs microarray. Quantitative real-time PCR (qPCR) was used to verify the results of the circRNA microarray. The role of circular RNA in intracranial aneurysm rupture was assessed in vitro . MTT assay, CCK-8 assay, Caspase3/7 assay, assay of cell apoptosis and Celigo wound healing was conducted to evaluate the relationship between circular RNA and the rupture of human intracranial aneurysms. Results: A total of 13,175 circRNA genes were detected. Among them 63 circRNAs upregulated and 54 circRNAs downregulated significantly in ruptured intracranial aneurysms compared with un-ruptured intracranial aneurysms ( p < 0.05 Fold Change > 1.5). Five upregulated circRNAs were selected for further study (hsa&#95;circ&#95;0001947, hsa&#95;circ&#95;0043001, hsa&#95;circ&#95;0064557, hsa&#95;circ&#95;0058514, hsa&#95;circ&#95;0005505). The results of qPCR showed only hsa&#95;circ&#95;0005505 significantly upregulated ( p < 0.05). The expression of hsa&#95;circ&#95;0005505 was higher in ruptured intracranial aneurysm tissues. And our in vitro data showed that hsa&#95;circRNA&#95;005505 promotes the proliferation, migration and suppresses the apoptosis of vascular smooth muscle cell. Conclusion: This study revealed an important role of hsa&#95;circ&#95;0005505 in the proliferation, migration and apoptosis of vascular smooth muscle cell, and indicated that hsa&#95;circ&#95;0005505 may associate with the pathological process of intracranial aneurysms., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Chen, Yang, Yang, Liu, Li, Wu, Wang and Wang.)

Background and Purpose: The effect of antiplatelet therapy (APT) on early postoperative rehemorrhage and outcomes of patients with spontaneous intracerebral hemorrhage (ICH) is still unclear. This study is to evaluate the effect of preoperative APT on early postoperative rehemorrhage and outcomes in ICH patients., Methods: This was a multicenter cohort study. ICH patients undergoing surgery were divided into APT group and no antiplatelet therapy (nAPT) group according to whether patients received APT or not. Chi-square test, t -test, and Mann-Whitney U test were used to compare the differences in variables, postoperative rehematoma, and outcomes between groups. Multivariate logistics regression analysis was used to correct for confounding variables, which were different in group comparison., Results: One hundred fifty ICH patients undergoing surgical treatment were consecutively included in this study. Thirty five (23.33%) people were included in the APT group, while 115 (76.67%) people were included in the nAPT group. The incidence of early postoperative rehemorrhage in the APT group was significantly higher than that in the nAPT group (25.7% VS 10.4%, p = 0.047 < 0.05). After adjustment for age, ischemic stroke history, and ventricular hematoma, preoperative APT had no significant effect on early postoperative rehemorrhage ( p = 0.067). There was no statistical difference between the two groups in early poorer outcomes ( p = 0.222) at 14 days after surgery. After adjustment for age, ischemic stroke history, and ventricular hematoma, preoperative APT also had no significant effect on early poorer modified Rankin Scale (mRS) ( p = 0.072)., Conclusion: In conclusion, preoperative APT appears to be safe and have no significant effect on early postoperative rehematoma and outcomes in ICH patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Yang, Liu, Mo, Wang, Li, Wu, Jiang, Yang, Guo, Yang, Zhang, Liu, Cao and Wang.)

Background: Potential neurovascular uncoupling (NVU) related to perinidal angiogenesis (PA) of brain arteriovenous malformations (AVMs) may cause inappropriate presurgical mapping using functional magnetic resonance imaging (fMRI), resulting in overconfident resection and postoperative morbidity., Purpose: To evaluate the potential impact of PA upon fMRI blood oxygen level-dependent signal in the periphery of AVMs., Study Type: Prospective., Population: Twenty-one patients with AVMs located in the primary sensorimotor cortex (SM1) undergoing task-based fMRI (hand motor), and 19 patients with supratentorial AVMs undergoing resting-state fMRI., Field Strength/sequence: 3.0T, echo-planar, time-of-flight, and magnetization-prepared rapid gradient-echo., Assessment: The presence of PA was determined by three observers (Y.C., J.W., and X.C.) according to digital subtraction angiography and MR angiography. Interhemispheric asymmetry of fMRI activations contralateral to hand movements was evaluated with the interhemispheric ratio of the average t-value within ipsilesional SM1 to contralesional SM1. Regional homogeneity (ReHo) and fractional amplitude of low-frequency fluctuations (fALFF) were extracted from ring-shaped perinidal regions and contralateral homologous regions, and the corresponding interhemispheric ratios were calculated. The effect of PA on the interhemispheric asymmetry of motor activations, ReHo, and fALFF was estimated., Statistical Tests: Pearson analysis, paired and independent t-test, multiple linear regression, Friedman test, and factorial analysis of variance were used., Results: Motor activations were significantly reduced in ipsilesional SM1 compared to contralesional SM1 (P < 0.05). The presence of PA was the independent predictor of activation loss in ipsilateral SM1(P < 0.05). Furthermore, perinidal regions exhibited reduced ReHo compared to the homologous regions (P < 0.05). PA was significantly associated with the decline of ReHo and fALFF in perinidal regions (P < 0.05, for both)., Data Conclusion: The presence of PA can predict perinidal NVU that may confound the interpretation of both task-based and resting-state fMRI, highlighting the importance of alternative approaches of brain functional localization in improving treatment of AVMs., Level of Evidence: 2 TECHNICAL EFFICACY STAGE: 2., (© 2020 International Society for Magnetic Resonance in Medicine.)

Background: CircRNAs have been found to play a crucial role in the pathological process of various kinds of diseases. However, the role of circRNAs in the formation and rupture of intracranial aneurysm is still unknown. Methods: Differentially expressed circRNAs profiles between superficial temporal arteries ( n = 5) and intracranial aneurysms ( n = 5) were analyzed using the Arraystar human circRNAs microarray. Quantitative real-time PCR was utilized to validate the differential expression of circDUS2. Fluorescence in situ hybridization (FISH) was meant for the location of circDUS2 in human brain vascular smooth muscle cell (HBVSMC). Structural analysis was used to speculate on the function of circDUS2. Results: Five hundred forty-three upregulated and 397 downregulated significantly in intracranial aneurysm as compared to superficial temporal arteries. Quantitative real-time PCR verified the elevated expression of the upregulated circDUS2. The FISH test revealed that circDUS2 is located in the cytoplasm of brain vascular smooth muscle cells. Conclusion: This study showed differential expression data of circRNAs between superficial temporal artery and intracranial aneurysm and revealed that circDUS2 is a potential molecular marker for intracranial aneurysm., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Chen, Yang, Yang, Liu, Li, Wu, Wang and Wang.)

Background: The reference intervals of thyroid hormone will change at different stages of pregnancy because of physiological alterations. On the other hand, the reference intervals of thyroid hormone will also change in different detection systems due to the manufacturer's methodology as well as a different race. The objective of this study was to establish the assay method- and trimester-specific reference intervals for thyroid-stimulating hormone, free thyroxine and free triiodothyronine for pregnant women in Chengdu., Methods: A prospective, population-based cohort study involved 23,701 reference samples of pregnant women during the three trimesters and 8646 non-pregnant women with pre-pregnancy clinical and laboratory tests. The 2.5th and 97.5th percentiles were calculated as the reference intervals for thyroid-stimulating hormone, free thyroxine and free triiodothyronine at each trimester of pregnant women according to ATA Guidelines., Results: The reference interval of thyroid-stimulating hormone in the 2.5th and 97.5th percentiles has a significant increasing trend from the first trimester, to second trimester and to third trimester, which was 0.08-3.79 mIU/L for the first trimester, and 0.12-3.95 mIU/L for the second trimester and 0.38-4.18 mIU/L for the third trimester, respectively (p < 0.001). However, the reference intervals of free thyroxine and free triiodothyronine in the 2.5th and 97.5th percentiles have significant decreasing trends from the first trimester, to second trimester and to third trimester, which were 11.87-18.83 pmol/L and 3.77-5.50 pmol/L for the first trimester, and 11.22-18.19 pmol/L and 3.60-5.41 pmol/L for the second trimester, and 10.19-17.42 pmol/L and 3.37-4.79 pmol/L for the third trimester, respectively (both p < 0.001)., Conclusion: It is necessary to establish assay method- and trimester-specific reference intervals for thyroid-stimulating hormone, free thyroxine, and free triiodothyronine because the reference intervals of these thyroid hormones are significantly different at different stages of pregnancy., (© 2021 The Authors. Journal of Clinical Laboratory Analysis published by Wiley Periodicals LLC.)

Background: Despite the capability of emergency surgery to reduce the mortality of severe spontaneous intracranial hemorrhage (SSICH) patients, the effect and safety of surgical treatment for severe spontaneous intracranial hemorrhage (SSICH) patients receiving long-term oral antiplatelet treatment (LOAPT) remains unclear. In consideration of this, the cohort study is aimed at figuring out the effect and safety of emergency surgery for SSICH patients on LOAPT., Methods: As a multicenter and prospective cohort study, it will be conducted across 7 representative clinical centers. Starting in September 2019, the observation is scheduled to be completed by December 2022, with a total of 450 SSICH patients recruited. The information on clinical, radiological, and laboratory practices will be recorded objectively. All of the patients will be monitored until death or 6 months after the occurrence of primary hemorrhage., Results: In this study, two comparative cohorts and an observational cohort will be set up. The primary outcome is the effect of emergency surgery, which is subject to assessment using the total mortality and comparison in the survival rate of SSICH patients on LOAPT between surgical treatment and conservative treatment. The second outcome is the safety of surgery, with the postoperative hemorrhagic complication which is compared between the operated SSICH patients on and not on LOAPT. Based on the observation of the characteristics and outcome of SSICH patients on LOAPT, the ischemic events after discontinuing LOAPT will be further addressed, and the coagulation function assessment system for operated SSICH patients on LOAPT will be established., Conclusions: In this study, we will investigate the effect and safety of emergency surgery for SSICH patients on LOAPT, which will provide an evidence for management in the future., Ethics and Dissemination: The research protocol and informed consent in this study were approved by the Institutional Review Board of Beijing Tiantan Hospital (KY2019-096-02). The results of this study are expected to be disseminated in peer-reviewed journals in 2023., Trial Registration: Name: Effect and safety of surgical intervention for severe spontaneous intracerebral hemorrhage patients on long-term oral antiplatelet treatment. ChiCTR1900024406 . Date of registration is July 10, 2019.

Objective: Intraoperative aneurysm rupture (IAR) could cause a poor outcome. This study aimed to investigate the relationship between IARs and postoperative cerebral infarctions (CIs)., Method: We retrospectively reviewed patients with asymptomatic unruptured intracranial aneurysms (UIAs) who received microsurgical clipping in two neurosurgical centers from January 2016 to June 2019. A propensity score matching was done to constitute a cohort. The data were collected regarding the clinical and radiological characteristics. The CI at 1-2 weeks and the functional outcome at two weeks after clipping were recorded. Differences between IAR patients with CIs and without CIs were compared. The relationship between the IARs and postoperative CIs was investigated by using logistic regression analysis., Results: This study yielded 96 UIAs patients, including 48 patients undergoing IARs and 48 patients not. Twenty patients with CIs at 1-2 weeks after clipping were identified. The rate of CIs in patients undergoing IARs was higher than that in patients not undergoing IARs (OR, 2.88; p = 0.038); moreover, the mRS was also worse in patients undergoing IARs (OR, 1.58; p = 0.015). For patients undergoing IARs, the significance was found in ischemic cerebrovascular disease (OR, 6.40; p = 0.048), Essen stroke risk score (OR, 2.14; p = 0.026), and severity of intraoperative rupture (OR, 5.63; p = 0.023). The multivariate logistic analysis demonstrated the major IARs (OR, 6.09; CI, 1.18-31.53; p = 0.031) as the independent risk factor related to postoperative CI., Conclusion: IARs could increase the risk of postoperative CIs and worsen the functional outcome, and major IAR was the independent risk factor related to the postoperative CIs., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: Early microsurgical clipping is recommended for ruptured intracranial aneurysms to prevent rebleeding. However, dilemma frequently occurs when managing patients with current acetylsalicylic acid (aspirin) use. This study aimed to examine whether aspirin use was associated with worse outcomes after early surgery for aneurysmal subarachnoid hemorrhage (aSAH)., Methods: We retrieved a consecutive series of 215 patients undergoing early microsurgical clipping within 72 h after aneurysmal rupture from 2012 to 2018 in the neurosurgery department of Beijing Tiantan Hospital. The medical records of each case were reviewed. Twenty-one patients had a history of long-term aspirin use before the onset of aSAH, and 194 patients did not. To reduce confounding bias, propensity score matching (PSM) was performed to balance some characteristics of the two groups. The intraoperative blood loss, postoperative hemorrhagic events, postoperative hospital stay, and functional outcome at discharge were compared between aspirin and non-aspirin group., Results: We matched all the 21 patients in aspirin group with 42 patients in non-aspirin group (1:2). Potential confounding factors were corrected between the two groups by PSM. No hospital mortality occurred after surgery. No significant differences were found in intraoperative blood loss (P = 0.540), postoperative hemorrhagic events (P > 0.999), postoperative hospital stay (P = 0.715), as well as functional outcome at discharge (P = 0.332) between the two groups., Conclusions: Our preliminary results showed that long-term low-dose aspirin use was not associated with worse outcomes. Early surgery can be safe for ruptured intracranial aneurysms in patients with long-term aspirin use.

Intracranial aneurysms can be classified into thick-walled aneurysms and thin-walled aneurysms according to their intraoperative appearances; previous publications have revealed that different kinds of intraoperative appearances were associated with intraoperative rupture and postoperative complications. Here, we tried to evaluate the association between hemodynamic features and aneurysm wall appearance using computational fluid dynamics (CFD) method. Forty-one consecutive patients with unruptured middle cerebral artery (MCA) bifurcation aneurysms were included in our study. Based on the appearances observed under the microscope, aneurysms were classified into two different types: thick-walled and thin-walled aneurysms. Preoperative computed tomographic angiography (CTA) was used for geometry reconstruction and CFD analysis. Morphological and hemodynamic parameters were compared between the two groups. Eighteen aneurysms were classified as thick-walled atherosclerotic ones according to their intraoperative appearances. Compared with thin-walled aneurysms, aneurysms with atherosclerotic changes had larger geometry parameters (aneurysm depth, maximum height, diameter, aspect ratio, size ratio), lower wall shear stress (WSS), and larger low WSS area ratio (LSAR). Thick-walled aneurysms characterized by atherosclerotic changes are associated with low WSS and larger LSAR. CFD may be a useful tool for discriminating the intraoperative appearance of cerebral aneurysms.

Aneurysm wall thickness is an important determinant of aneurysm progression and intra-procedural rupture. Several previous studies have evaluated the association between hemodynamic stress and aneurysm wall thickness, but conflicting results were obtained and no consensus has been achieved. According to the intraoperative findings, twenty-eight unruptured middle cerebral artery (MCA) aneurysms presented with thin-walled regions were enrolled in our study. Patient-specific 3D aneurysm models were constructed from preoperative computed tomography angiography (CTA) data and computational fluid dynamics (CFD) analyses were performed under pulsatile-flow conditions. Thin-walled regions of aneurysm dome were recognized by two experienced reviewers based on the intraoperative microscopy findings. Hemodynamic parameters derived from CFD analysis, including normalized wall shear stress (NWSS), normalized pressure (NP), the oscillatory shear index (OSI) and relative residence time (RRT), were compared between thin-walled regions and surrounding normal-thickness areas. Of the included aneurysms, twenty-eight pairs of thin-walled and normal surrounding regions were determined. Compared with surrounding tissues, thin-walled regions of aneurysm wall tended to present with higher pressure (1.232 vs 1.043, p < 0.05) and lower wall shear stress (0.693 vs 0.868, p < 0.05). Multivariate analysis revealed that elevated NP was significantly associated with thinning of the local aneurysm wall. Higher pressure and lower WSS were characteristic hemodynamic features associated with thinner regions of the aneurysm wall, elevated NP was an independent risk factor for local aneurysm wall thinning. CFD seems to be a useful method to estimate the location of thin-walled region, which will be helpful in reducing the risk of intraoperative rupture., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background: Surgical decision-making for brain arteriovenous malformations (AVMs) close to the corticospinal tract (CST) is always challenging. The purpose of this study was to develop a tractography-based grading scale to improve preoperative risk prediction and patient selection. Methods: We analyzed a consecutive, surgically treated series of 90 patients with AVMs within a 10-mm range from the CST demonstrated by preoperative diffusion tensor tractography. Poor motor outcome was defined as persistent postoperative limb weakness. We examined the predictive ability of nidus-to-CST distance (NCD), the closest CST level (CCL), deep perforating artery supply, as well as variables of the supplemented Spetzler-Martin grading system. Three logistic models were derived from different multivariable logistic regression analyses, of which the most predictive model was selected to construct a prediction grading scale. Receiver operating characteristic analysis was conducted to test the predictive accuracy of the grading scale. Results: Twenty-one (23.3%) patients experienced persistent postoperative limb weakness after a mean 2.7-year follow-up. The most predictive logistic model showed NCD ( P = 0.001), CCL ( P = 0.017), patient age ( P = 0.004), and AVM diffuseness ( P = 0.021) were independent predictors for poor motor outcome. We constructed the CLAD grading scale incorporating these predictors. The predictive accuracy of the CLAD grade was better compared with the supplemented Spetzler-Martin grade (area under curve = 0.84 vs. 0.68, P = 0.023). Conclusions: Both NCD and CCL predict motor outcome after resection of AVMs close to the CST. We propose the CLAD grading scale as an effective risk-prediction tool in surgical decision-making. Clinical Trial Registration: www.ClinicalTrials.gov, identifier: NCT01758211 and NCT02868008.

Objective: The aim of the present study is to investigate the potential morphological and hemodynamic risk factors related to intracranial aneurysms (IAs) rupture and establish a system to stratify the risk of IAs rupture to help the clinical decision-making. Methods: Patients admitted to our hospital for single-IAs were selected from January 2012 and January 2018. A propensity score matching was conducted to match patients. The morphological parameters were obtained from high solution CTA images, and the hemodynamic parameters were obtained in accordance with the outcomes of computational fluid dynamics (CFDs) simulation. Differences in the morphologic and hemodynamic parameters were compared. The significant parameters were selected to establish a novel scoring system (Intracranial Aneurysm Rupture Score, IARS). The comparison was drawn between the discriminating accuracy of IARS and the Rupture Resemblance Score (RRS) system to verify the value of IARS. Then, a group of patients with unruptured IAs was stratified into the high risk and low risk groups by IARS and RRS system separately and was followed up for 18-27 months to verify the value of IARS. The outcome of different stratifications was compared. Results: The matching process yielded 167 patients in each group. Differences of statistical significance were found in aneurysm length ( p = 0.001), perpendicular height (H) ( p < 0.001), aspect ratio (AR) ( p < 0.001), size ratio (SR) ( p < 0.001), deviated angle (DA) ( p < 0.001), normalized average wall shear stress (NWSSa) ( p < 0.001), wall shear stress gradient (WSSG) ( p < 0.001), low shear area ratio (LSAR) ( p = 0.01), and oscillatory shear index (OSI) ( p = 0.01). Logistic regression analysis further demonstrated that SR, DA, NWSSa, LSAR, and OSI were the independent risk factors of IAs rupture. SR, DA, LSAR, and OSI were finally selected to establish the IARS. Our present IARS showed a higher discriminating value (AUC 0.81 vs. 0.77) in comparison with the RRS (SR, NWSSa, and OSI). After follow-up, seven patients were subject to IAs rupture. 5/26 in high risk group stratified by IARS, yet 7/57 in high risk group stratified by RRS. The accuracy of IARS was further verified (19.2% vs. 12.3%, AUC for the IARS and the RRS was 0.723 and 0.673, respectively). Conclusion: SR, DA, NWSSa, LSAR, and OSI were considered the independent risk factors of IAs rupture. Our novel IARS showed higher accuracy in discriminating IA rupture in comparison with RRS.

Purpose: Investigate the expression of hepatocyte cell adhesion molecule (hepaCAM) and vascular endothelial growth factor (VEGF) mRNA in 55 cases of urothelial carcinoma to examine the potential relationship between hepaCAM and VEGF in urothelial carcinoma., Methods: Expression of hepaCAM and VEGF gene was determined by semiquantitative reverse transcriptase polymerase chain reaction (RT-PCR) in 55 paired urothelial carcinoma specimens. T24 cells stably expressing hepaCAM gene were established by Lipofectamine 2000. RT-PCR and western blot analysis were used to detect gene and protein expression of hepaCAM and VEGF before and after transfection. MTT test was used to detect the effect of hepaCAM gene on the cell proliferation., Results: RT-PCR showed that hepaCAM expression level was significantly lower, and VEGF was significantly higher in urothelial carcinoma tissues than in adjacent tissues (P < 0.05, P < 0.05). hepaCAM and VEGF were strongly correlated with tumor stage (P < 0.05, P < 0.05). Spearman correlation analysis showed lower hepaCAM level was associated with higher VEGF level (r = -0.277 P = 0.041). Experiments with T24 cells in vitro demonstrated the expression of VEGF mRNA and protein were significantly decreased after transfection of hepaCAM gene (P < 0.05, P < 0.05). Expression of hepaCAM resulted in a significant inhibition of T24 cells proliferation (P < 0.05)., Conclusion: There is a close relationship between hepaCAM and VEGF in urothelial carcinoma. hepaCAM may be defined as a new target for diagnosis and anticancer therapy.

Aim: We aimed to investigate the mechanisms of hepaCAM inactivation in transitional cell carcinoma of the bladder through the analysis of hepaCAM exon 2 methylation., Methods: The methylation of hepaCAM exon 2 and the expression of hepaCAM were determined by methylation-specific restriction PCR assay and RT-PCR in bladder cancer cells (T24, BIU-87) as well as in 55 paired bladder cancer specimens. The methylated bladder cancer cells were treated with 5-Aza- 2'-deoxycytidine (5-Aza-CdR), a demethylating agent. MTT was used to detect the proliferation of T24 and BIU-87 cells., Results: The proliferation of T24 and BIU-87 cells was suppressed by treatment with different concentrations of 5-Aza-CdR; the expression of hepaCAM was absent in T24 and BIU-87 cells, and we found that exon 2 of hepaCAM was methylated in the 2 cells. hepaCAM mRNA was re-expressed and the methylation status of hepaCAM exon 2 was reversed after treatment with 5-Aza-CdR. The expression of hepaCAM mRNA in bladder cancer tissues was significantly lower than that in adjacent tissues. The methylation rate of hepaCAM exon 2 was significantly higher in bladder cancer tissues than in adjacent tissues. The methylation of hepaCAM exon 2 was related to hepaCAM expression in bladder cancer tissues., Conclusions: Downregulation of hepaCAM expression plays an important role in the tumorigenesis and development of bladder cancer. DNA methylation may be important for downregulation of hepaCAM expression in bladder cancer., (Copyright © 2010 S. Karger AG, Basel.)