Steric Hindrance-Mediated Enzymatic Reaction Enable Homogeneous Dual Fluorescence Indicators Aptasensing of Hepatocellular Carcinoma CTCs.

Circulating tumor cells (CTCs) serve as important biomarkers in the liquid biopsy of hepatocellular carcinoma (HCC). Herein, a homogeneous dual fluorescence indicators aptasensing strategy is described for CTCs in HCC, with the core assistance of a steric hindrance-mediated enzymatic reaction. CTCs in the sample could specifically bind to a 5'-biotin-modified glypican-3 (GPC3) aptamer and remove the steric hindrance formed by the biotin-streptavidin system. This influences the efficiency of the terminal deoxynucleotidyl transferase enzymatic reaction. Then, methylene blue (MB) was introduced to react with the main product poly cytosine (polyC) chain, and trivalent cerium ion (Ce3+) was added to react with the byproduct pyrophosphate to form fluorescent pyrophosphate cerium coordination polymeric nanoparticles. Finally, the CTCs were quantified by dual fluorescence indicators analysis. Under optimized conditions, the linear range was 5 to 104 cells/mL, and the limits of detection reached 2 cells/mL. Then, 40 clinical samples (15 healthy and 25 HCC patients) were analyzed. The receiver operating characteristic curve analysis revealed an area under the curve of 0.96, a sensitivity of 92%, and a specificity of 100%. Therefore, this study established a sensitive and accurate CTCs sensing system for clinical HCC patients, promoting early tumor diagnosis.

Nanoarchitectonics-Assisted Simultaneous Fluorescence Detection of Urinary Dual miRNAs for Noninvasive Diagnosis of Prostate Cancer.

Herein, we report a fluorescence strategy for the homogeneous and simultaneous analysis of urine miRNA-375 and miRNA-148a. The target miRNAs in urine bonded the devised dumbbell-shaped "C-Ag+-C" and "T-Hg2+-T" hairpin structures that could trigger cascade enzyme-free amplification. Then, the fluorescent CdTe quantum dots (QDs) and carbon dots (CDs) could selectively recognize Ag+ and Hg2+, to quantify the dual miRNAs concurrently. Under optimized conditions, the linear range was from 0.1 to 1000 fM and the limits of detection (LOD) for dual miRNAs reached 30 and 25 aM, respectively. The practicality was further evaluated with 45 clinical urine samples including prostate cancer (PC) and other patients, and the results were consistent with the clinical polymerase chain reaction (PCR) kit and ultrasonic and pathological findings. The receiver operating characteristic (ROC) curve analysis showed that the estimates of the area under the curve (AUC) were 0.739 for the serum prostate-specific antigen (PSA) and 0.941 for miRNA-375 and 0.946 for miRNA-148a. The sensitivity and specificity reached 75 and 100% for miRNA-375 and 71 and 94% for miRNA-148a, respectively, which was better than serum PSA. This strategy constructed a reliable system for dual miRNA detection in urine samples and proposed new insights into the rapid and noninvasive diagnosis of PC.

Serum interleukin-1 is a new biomarker to predict the risk of rebleeding of ruptured intracranial aneurysm after admission.

Interleukin-1 (IL-1) could induce inflammation of the aneurysm wall, which might be related to intracranial aneurysm rupture. The aim of this study was to investigate whether IL-1 could serve as a biomarker to predict the risk of rebleeding after admission. Data between January 2018 and September 2020 were collected from patients with ruptured intracranial aneurysms (RIAs) and were retrospectively reviewed. The serum IL-1ß and IL-1ra levels were detected using a panel, and IL-1 ratio was calculated as the log10 (IL-1ra/IL-1ß). The predictive accuracy of IL-1 compared with previous clinical morphology (CM) model and other risk factors were evaluated by the c-statistic. Five hundred thirty-eight patients were finally included in the study, with 86 rebleeding RIAs. The multivariate Cox analysis confirmed aspect ratio (AR) > 1.6 (hazard ratio (HR), 4.89 [95%CI, 2.76-8.64], P < 0.001), size ratio (SR) > 3.0 (HR, 2.40 [95%CI, 1.34-4.29], P = 0.003), higher serum IL-1ß (HR, 1.88 [95%CI, 1.27-2.78], P = 0.002), and lower serum IL-1ra (HR, 0.67 [95%CI, 0.56-0.79], P < 0.001) as the independent risk factors for rebleeding after admission. According to the c-statistics, the IL-1 ratio had the highest predictive accuracy (0.82), followed by IL-1ra and IL-1ß (0.80), AR > 1.6 (0.79), IL-1ra (0.78), IL-1ß (0.74), and SR > 3.0 (0.56), respectively. Subgroup analysis based on AR and SR presented similar results. The model combining IL-1 ratio and CM model showed higher predictive accuracy for the rebleeding after admission (c-statistic, 0.90). Serum IL-1, especially IL-1 ratio, could serve as a biomarker to predict the risk of rebleeding after admission.

OGG1 contributes to hepatocellular carcinoma by promoting cell cycle-related protein expression and enhancing DNA oxidative damage repair in tumor cells.

BACKGROUND: This study aimed to analyze the expression of 8-oxoguanine DNA glycosylase (OGG1) in patients with hepatocellular carcinoma (HCC) and its effect on prognosis by bioinformatics techniques and to determine its possible carcinogenic mechanism through data mining. METHODS: The difference in OGG1 expression between healthy people and HCC patients was searched and analyzed by TCGA and GEO databases, and the effect of OGG1 on prognosis was judged by survival analysis. Meanwhile, the possible molecular mechanism of OGG1 in the tumorigenesis and development of HCC was explored by GO analysis, KEGG analysis, immune infiltration analysis, protein-protein interaction network, promoter methylation analysis, and so forth. Quantitative polymerase chain reaction (qPCR) was used to examine the gene expression in 36 pairs of HCC tissues and adjacent tissues. RESULTS: The expression of OGG1 in HCC patients was higher than that in healthy people, and the overexpression of OGG1 might stimulate cell proliferation by increasing the activity of cell cycle-related proteins. CONCLUSION: The alteration of OGG1 was significantly correlated with the tumorigenesis and development of HCC. OGG1 is expected to be a new biomarker for evaluating the prognosis of HCC and a new target for the treatment of HCC.

Aspirin does not affect hematoma growth in severe spontaneous intracranial hematoma.

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.

A nomogram to predict the risk of postoperative intracranial rebleeding in patients with spontaneous intracranial hematoma.

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.

Preoperative antiplatelet therapy may be a risk factor for postoperative ischemic complications in intracranial hemorrhage patients.

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.

Perinidal Angiogenesis Is a Predictor for Neurovascular Uncoupling in the Periphery of Brain Arteriovenous Malformations: A Task-Based and Resting-State fMRI Study.

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.

Altered expression profile of BAFF receptors on peripheral blood B lymphocytes in Graves' disease.

BACKGROUND: B lymphocyte activating factor (BAFF) is a growth factor regulating B lymphocytes survival and maturation. Serum BAFF levels were elevated in patients affected with autoimmune thyroid diseases (AITD), including Graves' disease (GD) and Hashimoto's thyroiditis (HT). The aim of this study is to explore the association of expression levels of BAFF and its receptors with AITD. METHODS: Fifty-two GD patients, 39 Hashimoto's thyroiditis (HT) patients and 23 healthy controls (HC) were recruited in this study. Serum BAFF levels were measured by ELISA. Expression of BAFF receptors, including BAFF receptor 3 (BR3) and transmembrane activator and calcium-modulating and cyclophilin ligand interactor (TACI), on B lymphocytes were analyzed by flowcytometry. Effects of steroids on serum BAFF levels and expression of BR3 and TACI were also observed in 10 patients with Graves' orbitopathy (GO) receiving steroids therapy. RESULTS: Serum BAFF levels were significantly elevated from 0.93 ± 0.24 ng/ml in HC to 1.18 ± 0.33 ng/ml in GD (P = 0.0027) and 1.02 ± 0.24 ng/ml in HT (P = 0.0331). BR3 expression on peripheral B lymphocytes were elevated in GD (mean MFI: 4.52 ± 2.06 in GD vs. 3.00 ± 0.87 in HC, P = 0.0015), while TACI expression on peripheral B lymphocytes were decreased in GD without significance (mean MFI: 7.96 ± 4.06 in GD vs. 9.10 ± 3.37 in HC, P = 0.1285). Expression of BR3 and TACI was not changed significantly in HT patients. Steroids significantly suppressed serum BAFF concentrations (from 1.18 ± 0.27 ng/ml to 0.97 ± 0.10 ng/ml, P = 0.0364) and BR3 expression in GO patients (mean MFI from 6.26 ± 4.91 to 4.05 ± 1.58, P = 0.0083). CONCLUSIONS: Altered expression of BAFF and its receptor may mediate the autoimmunity in GD. Restoring the normal expression profile of receptors for BAFF could be a new strategy to treat GD.

A novel methodology of the myeloid-derived suppressor cells (MDSCs) generation with splenic stroma feeder cells.

Myeloid-derived suppressor cells (MDSCs) are a significant obstacle for immunotherapy of cancer. It is of great clinical relevance to study the mechanism of MDSCs accumulation in mouse spleens and establish a stable method to obtain high-purity MDSCs in vitro for further research. Here, we established a new method for amplifying a large number of highly pure MDSCs in vitro. To mimic the microenvironment of MDSCs development in vivo, mouse splenic stroma feeder cells and serum-free medium containing granulocyte-macrophage colony stimulating factor (GM-CSF) were used to induce myeloid precursors in mouse bone marrow cells, which differentiate into MDSCs. Development and immunological functions of the cells were monitored both in vivo and in vitro. A total of 4 × 108 MDSCs could be obtained from the bone marrow from one mouse, the ratio of CD11b+Gr-1+ MDSCs could reach 93.8% ± 3.3% after nine days of culture in vitro. Cultured MDSCs maintained a similar immunophenotype with MDSCs found in tumor-bearing mice. Colony forming assay in vitro and in vivo demonstrated that these were myeloid precursor cells. These cells generated high levels of reactive oxygen species and arginase 1 to prevent proliferation of CD8+ T cells in vitro. These also increased regulatory T (Treg) cells in blood while promoting the growth of lymphoma in vivo. In addition, cultured MDSCs effectively inhibited acute graft-versus-host disease (aGVHD). Our findings suggest that mouse splenic stroma plays an important role in the generation of MDSCs and represent a preliminary mechanism for the accumulation of MDSCs in spleens, and thereby lay the foundation for basic research and the clinical application of MDSCs.

Multidimensional predicting model of intracranial aneurysm stability with backpropagation neural network: a preliminary study.

OBJECTIVES: The stability of intracranial aneurysms (IAs) may involve in multidimensional factors. Backpropagation (BP) neural network could be adopted to support clinical work. This preliminary study aimed to delve into the feasibility of BP neural network in assessing the risk of IA rupture/growth and to prove the advantage of multidimensional model over single/double-dimensional model. METHODS: Thirty-six IA patients were recruited from a prospective registration study (ChiCTR1900024547). All patients were followed up until aneurysm ruptured/grew or 36 months after being diagnosed with the IAs. The multidimensional data regarding clinical, morphological, and hemodynamic characteristics were acquired. Hemodynamic analyses were conducted with patient-specific models. Based on these characteristics, seven models were built with BP neural network (the ratio of training set to validation set as 8:1). The area under curves (AUC) was calculated for subsequent comparison. RESULTS: Forty-five characteristics were determined from 36 patients with 37 IAs. In the models based on the single dimension of IA characteristics, only morphological characteristics exhibited high performance in assessing 3-year IA stability (AUC = 0.703, P = 0.035). Among the models integrating two dimensions of IA characteristics, clinical-morphological (AUC = 0.731, P = 0.016), clinical-hemodynamic (AUC = 0.702, P = 0.036), and morphological-hemodynamic (AUC = 0.785, P = 0.003) models were capable of assessing the risk of 3-year IA rupture/growth. Moreover, the models including all three dimensions exhibited the maximum predicting significance (AUC = 0.811, P = 0.001). CONCLUSION: The present preliminary study reported that BP neural network might support assessing the 3-year stability of IAs. Models based on multidimensional characteristics could improve the assessment accuracy for IA rupture/growth.

Emergency surgery is an effective way to improve the outcome of severe spontaneous intracerebral hemorrhage patients on long-term oral antiplatelet therapy.

The necessity of emergency surgery for severe spontaneous intracerebral hemorrhage (SSICH) patients on long-term oral antiplatelet therapy (LOAPT) remains unclear. The aim of this study was to investigate the effect and safety of emergency surgery for SSICH patients on LOAPT (SSICH-LOAPT patients). In this study, a retrospective review of patients admitted to our institution for SSICH from January 2012 to December 2018 was conducted. The collected data included demographic, clinical, and surgical information. The outcome was recorded at 3 months after primary hemorrhage. The outcome of SSICH-LOAPT patients receiving emergency surgery and conservative treatment were compared. The risk of postoperative intracranial bleeding (PIB) in operated SSICH-LOAPT patients was further investigated. A total of 522 SSICH patients were retrospectively reviewed, including 181 SSICH-LOAPT patients and 269 operated patients. The total mortality and in-hospital mortality were 40.6% and 19.3%, respectively. As compared with SSICH-LOAPT patients receiving conservative treatment, the operated SSICH-LOAPT patients showed a lower total (p = 0.043) and in-hospital mortality (p = 0.024). When compared with operated patients not on LOAPT, the operated patients on LOAPT exhibited a higher rate of PIB (OR, 2.34; 95% CI 1.14-4.79; p = 0.018). As demonstrated by the multivariate logistic analysis, dual antiplatelet therapy were independent risk factors associated with PIB in operated SSICH-LOAPT patients (OR, 3.42; CI, 1.01-11.51; p = 0.047). Despite of increasing risk of PIB, emergency surgery could improve the outcome of SSICH-LOAPT patients as it could be effective in reducing mortality. Dual antiplatelet therapy was the independent risk factor related to the PIB in operated SSICH-LOAPT patients.

A scoring system to discriminate blood blister-like aneurysms: a multidimensional study using patient-specific model.

Presurgical discrimination of blood blister-like aneurysms (BBAs) can assist neurosurgeons in clinical decision-making. The aim of this study was to investigate the characteristics of BBAs and construct a useful tool to distinguish BBAs. This study reviewed patients with small/median, hemispherical, and wide-necked aneurysms of the internal carotid artery in our institution. BBAs were identified via their intraoperative findings. A hemodynamic analysis was performed using a patient-specific model. The independent risk factors of BBAs were investigated using a logistic analysis. A scoring system was then established to discriminate BBAs, in which its predicting value was analyzed using receiver operating characteristic (ROC) analysis. A total of 67 aneurysms comprising 21 BBAs were enrolled. Comparing features between BBAs and non-BBAs, statistical significances were found in the aspect ratio (AR), height-to-width ratio, aneurysm angle (AA), wall shear stress gradient (WSSG), and normalized wall shear stress average. A multivariate logistic analysis identified AR (OR = 0.29, p = 0.021), WSSG (OR = 1.54, p = 0.017) and AA (OR = 2.49, p = 0.039) as independent risk factors for BBAs. A scoring system was constructed using these parameters, effectively distinguishing BBAs (AUC = 0.931, p < 0.01). Our multidimensional scoring system may effectively assist in the discrimination of BBAs from wide-necked non-BBAs.

Hemodynamic findings associated with intraoperative appearances of intracranial aneurysms.

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.

Altered Brain Structural Networks in Patients with Brain Arteriovenous Malformations Located in Broca's Area.

Focal brain lesions, such as stroke and tumors, can lead to remote structural alterations across the whole-brain networks. Brain arteriovenous malformations (AVMs), usually presumed to be congenital, often result in tissue degeneration and functional displacement of the perifocal areas, but it remains unclear whether AVMs may produce long-range effects upon the whole-brain white matter organization. In this study, we used diffusion tensor imaging and graph theory methods to investigate the alterations of brain structural networks in 14 patients with AVMs in the presumed Broca's area, compared to 27 normal controls. Weighted brain structural networks were constructed based on deterministic tractography. We compared the topological properties and network connectivity between patients and normal controls. Functional magnetic resonance imaging revealed contralateral reorganization of Broca's area in five (35.7%) patients. Compared to normal controls, the patients exhibited preserved small-worldness of brain structural networks. However, AVM patients exhibited significantly decreased global efficiency (p = 0.004) and clustering coefficient (p = 0.014), along with decreased corresponding nodal properties in some remote brain regions (p < 0.05, family-wise error corrected). Furthermore, structural connectivity was reduced in the right perisylvian regions but enhanced in the perifocal areas (p < 0.05). The vulnerability of the left supramarginal gyrus was significantly increased (p = 0.039, corrected), and the bilateral putamina were added as hubs in the AVM patients. These alterations provide evidence for the long-range effects of AVMs on brain white matter networks. Our preliminary findings contribute extra insights into the understanding of brain plasticity and pathological state in patients with AVMs.

Intracranial aneurysm rupture score may correlate to the risk of rebleeding before treatment of ruptured intracranial aneurysms.

BACKGROUND AND OBJECTIVE: Aneurysm rebleeding after rupture can result in a catastrophic outcome with high mortality and morbidity. In this study, we evaluated the correlation of IARS (intracranial aneurysm rupture score) and aneurysm rebleeding. The aim of this study was to explore the clinical utility of IARS for better clinical decision-making. METHOD: The patients with ruptured intracranial aneurysms between January 2017 and September 2018 were reviewed. Propensity scoring match was performed to construct a cohort. The morphological and hemodynamic parameters were obtained. The difference between stable aneurysms and rebleeding aneurysms was compared. Subsequently, the correlation of IARS and aneurysm rebleeding was studied. RESULTS: The matching process constructed a cohort, including 5 rebleeding aneurysms and 15 stable aneurysms. By comparing the difference between stable aneurysms and rebleeding aneurysms, the statistical significance was found in diameter of neck (p = 0.036), aspect ratio (p = 0.004) and size ratio (p = 0.029), normalized wall shear stress average (p = 0.026), low shear area ratio (p = 0.028), oscillatory shear index (OSI) (p = 0.031), and deviated angle (p = 0.025). The IARS here had a strong correlation with the aneurysm rebleeding, and the interval from the first bleeding to the rebleeding tended to shorten with the increase of IARS (R = 0.715, p = 0.027). IARS had a good predicting value for the aneurysm rebleeding (area under the curve = 0.756, p < 0.001). CONCLUSION: Based on this preliminary study, intracranial aneurysm rupture score may correlate to the rebleeding in ruptured aneurysms. For ruptured aneurysms with high IARS scores, surgery should be given priority, and medical treatment is not recommended.

Tenacigenin B Has Anti-Tumor Effect in Lymphoma by In Vitro and In Vivo Study.

BACKGROUND The aim of this study was to examine the effects and mechanisms of tenacigenin B in lymphoma treatment by in vitro and in vivo experiment. MATERIAL AND METHODS Raji cells were treated by difference methods. Measuring the cell proliferation of difference groups was done by MTT assay; cell apoptosis and cell cycle of difference groups were evaluated by flow cytometer; relative mRNA expression was evaluated by real-time polymerase chain reaction (RT-PCR), and relative protein expressions were measured by western blot assay in an in vitro study. In an in vivo study, we used a nude mice model to explore the anti-tumor effects and mechanism of tenacigenin B. Cell apoptosis was measured by TUNEL assay; relative protein expressions were evaluated by immunohistochemistry assay, and relative mRNA expression was evaluated by RT-PCR. In addition, the blood components of difference groups were measured. RESULTS Compared with the Normal control group, the cell proliferation rate was significantly downregulated, with cell apoptosis significantly increasing with G1 phase in the Drug group and the si-Aurora-A group (P<0.05, respectively). The PTEN, PI3K, AKT, P53, and P21 mRNA and protein expressions of the Drug group, the si-Aurora-A group, and the si-Aurora-A+Drug group were significantly different (P<0.01, respectively), The tumor volume and weight of the Drug group, the si-Aurora-A group, and the si-Aurora-A+Drug group were significantly suppressed compared with the Normal group (P<0.01, respectively). The positive apoptosis cell number in the Drug group, the si-Aurora-A group, and si-Aurora-A+Drug group were increased compared with that of Normal group (P<0.01, respectively). CONCLUSIONS Tenacigenin B had anti-tumor effects on lymphoma via regulation of Aurora-A in vitro and in vivo.

Symptomatic and silent cerebral infarction following surgical clipping of unruptured intracranial aneurysms: incidence, risk factors, and clinical outcome.

Cerebral infarction (CI) associated with clipping of unruptured intracranial aneurysms (UIAs) has not been completely studied. The role of individual and operative characteristics is not known, and the risk of silent CI has not been well described. To determine the incidence, risk factors, and clinical outcome of postoperative CI, we retrospectively analyzed 388 consecutive patients undergoing clipping of UIAs between January 2012 and December 2015. We reviewed the pre- and postoperative computed tomography (CT) images of each patient. Postoperative CI was defined as a new parenchymal hypodensity in the vascular territory of treated artery. Patient-specific, aneurysm-specific, and operative variables were analyzed as potential risk factors. Functional outcome at discharge was assessed with the modified Rankin Scale (mRS). Postoperative CI was found in 49 (12.6%) patients, 29 of whom manifested neurological deficits. The incidences of symptomatic stroke and silent CI were 7.5 and 5.2%, respectively. Multivariate analysis showed that larger aneurysm size and history of hypertension were significantly associated with CI. Disability (mRS > 2) rate was 42.9% among patients with CI, which was substantially higher than that among patients without (0.9%). In conclusion, the incidence of CI following clipping of UIAs was not low. Larger aneurysm size and history of hypertension were independent risk factors. Postoperative symptomatic stroke correlated with an extremely high risk of disability. Silent CI was seemingly nondisabling, but the possible cognitive consequence is pending.

[Modified Shengma Biejia Decoction Combined with CAG Program for Elderly Acute Myeloid Leuke- mia Patients with Yin Deficiency Toxin Stasis Syndrome].

OBJECTIVE: To observe the efficacy and safety of modified Shengma Biejia Decoction (MSBD) combined with CAG program in treating elderly acute myeloid leukemia (AML) patients with yin deficiency toxin stasis syndrome (YDTSS). METHODS: Totally 46 elderly AML patients were assigned to the treatment group (24 cases; treated with MSBD + CAG) and the control group (22 cases; treated with CAG + placebos of Chinese medicine) according to random digit table. The therapeutic course of CM placebo or MSBD was 21 days. The clinical efficacy and adverse reactions were observed. Meanwhile, physical state (ECOG Score), transfusion dependency, and TCM syndrome score were compared before and after treatment. RESULTS: (1) The complete remission rate was 54% (13/24) and the objective response rate (ORR) was 71% (17/24) in the treatment group, obviously higher than those of the control group [36% (8/22); 54% (13/24)], with statistical difference (P = 0.036, 0.042). When comparing the efficacy based on risk level, the moderate and poor ORR was 71% (10/14) and 67% (6/9) in the treatment group, and 57% (8/14) and 33% (2/6) in the control group, with statistical difference between the two groups (P = 0.048; P = 0.010). (2) Compared with before treatment in the same group, the ECOG score significantly decreased, the average infusion time of red cells and platelets were markedly prolonged in the treatment group after treatment (P < 0.05). ECOG score, the average infusion time of red cells and platelets were significantly better in the treatment group than in the control group after treatment (P < 0.05). (3) Compared with before treatment in the same group, scores of fever, hemorrhage, and bone pain were markedly reduced in the control group (P < 0.05); scores of fever, fatigue, hemorrhage, dry mouth, and bone pain were markedly reduced in the treatment group (P < 0.05). Better effect in relief of fever, fatigue, hemorrhage, dry mouth, and so on was obtained in the treatment group than in the control group (P < 0.05). (4) In aspect of hematotoxicity, the incidence of neutropenia, anemia, thrombocytopenia was obviously lower in the treatment group than in the control group [29.2% (7/24) vs 54.5% (12/22); 16.7% (4/ 24) vs 45.5% (10/22); 33.3% (8/24) vs 63.6% (14/22); P < 0.05]. The incidence of fatigue and anorexia was obviously lower in the treatment group than in the control group [37.5% (9/24) vs 63.6% (14/22), 37.5% (9/24) vs 81.8% (18/22); P < 0.05]. CONCLUSION: MSBD combined with CAG program in treating elderly AML patients with YDTSS, with efficacy enhancing toxicity reducing effect, had distinct advantages in improving physical condition and clinical symptoms, and reducing transfusion dependency.

Nucleic Acid and Nanomaterial Synergistic Amplification Enables Dual Targets of Ultrasensitive Fluorescence Quantification to Improve the Efficacy of Clinical Tuberculosis Diagnosis.

Interferon-γ (IFN-γ) release assays (IGRAs) are constrained by the limited diagnostic performance of a single indicator and the excessive Mycobacterium tuberculosis (Mtb) antigen stimulation time. This study presents a simultaneous, homogeneous, rapid, and ultrasensitive fluorescence quantification strategy for IFN-γ and IFN-γ-induced protein 10 (IP-10). This method relies on the high-affinity binding of aptamers to IFN-γ and IP-10, the enzyme-free catalytic hairpin assembly reaction, and the heightened sensitivity of CdTe quantum dots to Ag+ and hairpin structure C-Ag+-C and carbon dots to Hg2+ and hairpin structure T-Hg2+-T. Under optimized conditions, the selectivity of IFN-γ and IP-10 was excellent, with a linear range spanning from 1 to 100 ag/mL and low limits of detection of 0.3 and 0.5 ag/mL, respectively. Clinical practicality was confirmed through testing of 57 clinical samples. The dual-indicator combination detection showed 92.8% specificity and 93.1% sensitivity, with an area under the curve of 0.899, representing an improvement over the single-indicator approach. The Mtb antigen stimulation time was reduced to 8 h for 6/7 clinical samples. These findings underscore the potential of our approach to enhance the efficiency and performance of a tuberculosis (TB) clinical diagnosis.