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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.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.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%,In conclusion, preoperative APT may be a risk factor for PICs in ICH patients undergoing surgical treatment significantly.

Simultaneous sensitive and cost-effective detection of multiple tumor markers has shown great potential for cancer diagnostics. Herein, we reported a simple enzyme-free parallel catalytic hairpin assembly (CHA) amplification strategy with

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-1β and IL-1ra levels were detected using a panel, and IL-1 ratio was calculated as the log10(IL-1ra/IL-1β). The predictive accuracy of IL-1 compared with previous clinical morphology (CM) model and other risk factors were evaluated by the c-statistic. 538 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 3.0 (HR, 2.40 [95%CI, 1.34–4.29], P = 0.003), higher serum IL-1β (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 1.6 (0.79), IL-1ra (0.78), IL-1β (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. Unique identifier: ChiCTR1900024406, retrospectively registered.

Shushu Qian,1,* Xuan Han,2,* Xiaocao Sha,1,* Fang Tian,1 Hong Huang,1 Pengjun Jiang,1 Guoshun Huang,1 Bangyun Ma,1 Hong Zhang,1 Yiye Zhu,1 Xuemei Sun1 1Jiangsu Province Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, Jiangsu, People’s Republic of China; 2School of Integrated Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xuemei Sun, Tel +86-25-86617141, Fax +86-25-86518690, Email 13913911666@qq.comPurpose: Cimicifuga dahurica (C. dahurica), which has been used in traditional oriental medicine for a long period, was reported to exert extensive antitumor activity, but the effect and molecular biological mechanism of C. dahurica on multiple myeloma (MM) has not been elaborated. Tumor-associated macrophages (TAMs) exhibit a sustained polarization between tumor killing M1 subtype and tumor supporting M2 subtype. And a lower ratio of M1/M2 is associated with tumor angiogenesis, proliferation and invasion. We explored the inhibitory effect of the aqueous extract of the root of C. dahurica (CRAE) on tumor growth by reprogramming macrophage polarization in the tumor microenvironment.Methods: Mice bearing SP2/0 multiple myeloma were treated with CRAE. Western blotting (WB), immunohistochemistry (IHC) and immunofluorescence staining were utilized to assess tumor growth and TAM populations. Macrophages were depleted by injection of clodronate liposomes to determine and measure the role of CRAE as an anti-tumor agent by targeting macrophages. To simulate tumor microenvironment, MM cells H929 and TAMs were co-cultured using the transwell co-culture system. By using CRAE as an immunoregulator in M2-like macrophages, we analyzed CRAE-treated macrophage-associated surface markers and cytokines by flow cytometry and WB.Results: The results indicated that CRAE treatment could reduce tumor burden of MM mice and a high degree of M1-like macrophages infiltration was detected in tumor tissues. In vitro co-culture system, CRAE significantly promoted the polarization of M2 to M1 phenotype, which led to the increase in apoptosis of myeloma cells. It was found that the M1 polarization induced by CRAE depended on the TLR4-MyD88-TAK1-NF-κB signal transduction.Conclusion: This study elucidated the anticancer mechanism of the aqueous extract of C. dahurica (CRAE) through reprogramming macrophage polarization and highlighted that CRAE could act as a potential novel option for cancer immunotherapy.Keywords: Cimicifuga dahurica, tumor-associated macrophages, macrophage polarization, multiple myeloma, tumor microenvironment

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.

Background Cytokine release syndrome (CRS) is a life-threatening complication of chimeric antigen receptor T cell (CAR-T) therapy. Macrophages/ monocytes are mediators of CRS. Tripterygium glycosides is an immunomodulator which could inhibit macrophages/ monocytes in animal models. Methods Two patients with relapsed and refractory hematological malignancies developed CRS after receiving CAR-T therapy. They received short-term tripterygium glycosides orally. Results Both patients showed rapid mitigation of fever with evidently decrease in elevated inflammatory cytokines within 72 hours. The patients' monocytes diminished remarkably, while CAR-T cells were neglectably affected. Treatment of 30 ng/mL triptolide in ex vivo cultured patients' blood for 24 hours selectively deplete over half of monocytes. Single cell RNA sequencing suggested selective depletion of CD14+CD16+ monocytes with decreased pro-inflammatory cytokines. Conclusions The low-cost and orally available tripterygium glycosides could be a promising alternative for CAR-T induced CRS, as well as other diseases complicated with CRS, e.g., coronavirus disease 2019.

Aneurysm wall remodeling (AWR) is an important pathological characteristic in aneurysm wall, which was characterized by abnormal histological structure and inflammation infiltration. In the present study, the aim is to determine the relationships of morphological-hemodynamic characteristics, inflammation, and AWR in intracranial aneurysms (IAs), as well as the pathological basis of morphological-hemodynamic predictors to achieve IA development. For this end, 113 unruptured IAs were prospectively collected from 110 cases. In addition, patient-specific computational fluid dynamics and geometry were adopted to determine hemodynamic and morphological parameters. Moreover, Hematoxylin-Eosin staining was performed to identify the AWR. By performing immunofluorescence, the inflammatory markers were detected. Masson staining was conducted to characterize the characteristics of atherosclerosis in aneurysm wall. To demonstrate the parameters regarding the AWR, a multivariate logistic analysis was conducted. Besides, correlation analyses were conducted to verify the relationship between morphological-hemodynamic and pathological characteristics. For 113 unruptured IAs, no difference was identified in baseline information. AWR was demonstrated in 92 (81.4%) IAs. To be specific, the aneurysm size (odds ratio (OR), 2.63; confidence interval (CI), 1.04-6.67; P = 0.041), size ratio (SR; OR, 1.95; CI, 1.38-2.76; P < 0.001), normalized wall shear stress average (NWSSA; OR, 0.05; CI, 0.01-0.15; P = 0.007), and relative resident time (RRT; OR, 1.28; CI, 1.07-1.53; P = 0.007) were proved as the factors of AWR. As revealed from the results of immunofluorescence, aneurysm size, SR, NWSSA, and RRT were significantly correlated with the level of inflammation in IA tissues. Furthermore, Masson staining revealed that atherosclerosis area in IA tissues and NWSSA was correlated with RRT. In this study, SR, NWSSA, and RRT were demonstrated as the risk factors of AWR. The mentioned parameters could also reflect the characteristics of inflammation and atherosclerosis in aneurysm wall as well. This study revealed that biomechanical stress and inflammation in aneurysm wall are correlated, which might suggest the pathological evidence of morphological-hemodynamic predictors for IA development.

Background: Natural killer/T-cell lymphoma(NKTCL) is a highly aggressive non-Hodgkin's lymphoma that is prevalent in Asia and South America. However, given the high malignancy grade, rapid clinical progress and poor long‐term prognosis of NKTCL, exploring the potential mechanism of NKTCL is of great significance for the development of drugs for NKTCL. Case presentation: We presented a case of a woman who was admitted to hospital with multiple enlarged lymph nodes and high white blood cells ,and flow cytometry examination revealed CD56 bright, CD16 dim, surface CD3-, cytoplasmic CD3+, CD2+, CD7-, HLA-DR+, CD57-, TCRβ and TCRγ genes rearrangement. No further pathological diagnosis was made because the patient's condition did not meet the need for biopsy, deteriorated rapidly and died within three days after admission; NKTCL was diagnosed based on clinical manifestations. Whole exome sequencing revealed that the NOTCH4, KMT2D, and S100A16 mutations were closely related to the occurrence and progression of NKTCL. In addition, this patient was EBV-negative. Conclusions: We mainly diagnosed NKTCL by exclusion, and the pathogenesis is complex or not limited to EBV. The discovery of new mutant genes will provide potential impact on clinical diagnosis and research guidance for its pathogenesis, prognosis, drug resistance and targeted therapy.

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.

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

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.

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.

The prevalence of allergic rhinitis has exhibited an upward trend, and diabetes is a common endocrine metabolic disorder. Treatment of allergic rhinitis complicated with diabetes has been marginally explored. This study aimed to observe the effect of rupatadine fumarate combined with acupoint application in the treatment of allergic rhinitis complicated with diabetes and its effect on serum IgE levels. Totally 80 patients with allergic rhinitis complicated with diabetes admitted to our hospital from December 2019 to December 2020 were recruited and assigned to receive either rupatadine fumarate (control group) or rupatadine fumarate plus acupoint application (research group). The clinical observation indexes of the two groups of patients before and after treatment were analyzed, and the clinical efficacy of the two groups was evaluated. Rupatadine fumarate plus acupoint application was associated with a significantly higher efficacy (23 cases of markedly effective, 14 cases of effective, and 3 cases of ineffective) versus rupatadine fumarate alone (14 cases of markedly effective, 16 cases of effective, and 10 cases of ineffective) (χ2 = 4.501, p = 0.034). The immunoglobulin E (IgE) and nasal mucosal eosinophils (EOS) levels of the two groups of patients after treatment decreased significantly, and the research group had lower results ( p p p p > 0.05). Rupatadine fumarate plus acupoint application may offer a viable alternative for the treatment of allergic rhinitis as it alleviates the clinical symptoms, improves the treatment efficiency, and enhances the anti-allergic effect of the drug, with a high safety profile.

Mice bearing SP2/0 multiple myeloma were treated with CRAE. Western blotting (WB), immunohistochemistry (IHC) and immunofluorescence staining were utilized to assess tumor growth and TAM populations. Macrophages were depleted by injection of clodronate liposomes to determine and measure the role of CRAE as an anti-tumor agent by targeting macrophages. To simulate tumor microenvironment, MM cells H929 and TAMs were co-cultured using the transwell co-culture system. By using CRAE as an immunoregulator in M2-like macrophages, we analyzed CRAE-treated macrophage-associated surface markers and cytokines by flow cytometry and WB.The results indicated that CRAE treatment could reduce tumor burden of MM mice and a high degree of M1-like macrophages infiltration was detected in tumor tissues. In vitro co-culture system, CRAE significantly promoted the polarization of M2 to M1 phenotype, which led to the increase in apoptosis of myeloma cells. It was found that the M1 polarization induced by CRAE depended on the TLR4-MyD88-TAK1-NF-κB signal transduction.This study elucidated the anticancer mechanism of the aqueous extract of

Background Rebleeding can cause a catastrophic outcome after aneurysmal subarachnoid hemorrhage. A clinical + morphology nomogram was promoted in our previous study to assist in discriminating the rupture intracranial aneurysms (RIAs) with a high risk of rebleeding. The aim of this study was to validate the predictive accuracy of this nomogram model. Method The patients with RIAs in two medical centers from December 2020 to September 2021 were retrospectively reviewed, whose clinical and morphological parameters were collected. The Cox regression model was employed to identify the risk factors related to rebleeding after their admission. The predicting accuracy of clinical + morphological nomogram, ELAPSS score and PHASES score was compared based on the area under the curves (AUCs). Results One hundred thirty-eight patients with RIAs were finally included in this study, 20 of whom suffering from rebleeding after admission. Hypertension (hazard ratio (HR), 2.54; a confidence interval of 95% (CI), 1.01–6.40; P = 0.047), bifurcation (HR, 3.88; 95% CI, 1.29–11.66; P = 0.016), and AR (HR, 2.68; 95% CI, 1.63–4.41; P < 0.001) were demonstrated through Cox regression analysis as the independent risk factors for rebleeding after admission. The clinical + morphological nomogram had the highest predicting accuracy (AUC, 0.939, P < 0.01), followed by the bifurcation (AUC, 0.735, P = 0.001), AR (AUC, 0.666, P = 0.018), and ELAPSS score (AUC, 0.682, P = 0.009). Hypertension (AUC, 0.693, P = 0.080) or PHASES score (AUC, 0.577, P = 0.244) could not be used to predict the risk of rebleeding after admission. The calibration curve for the probability of rebleeding showed a good agreement between the prediction through clinical + morphological nomogram and actual observation. Conclusion Hypertension, bifurcation site, and AR were independent risk factors related to the rebleeding of RIAs after admission. The clinical + morphological nomogram could help doctors to identify the high-risk RIAs with a high predictive accuracy.

Microsurgical treatment of unruptured giant intracranial aneurysms (GIAs) is challenging. Although previous studies regarded clipping as the first option to repair GIAs, quite a number of GIAs are not clippable. We conducted this study to evaluate the postoperative complications and long-term outcome of patients with unruptured GIAs treated by different microsurgical modalities. We retrospectively reviewed 505 consecutive patients with unruptured intracranial aneurysms (UIAs) who were surgically treated in our department from 2012 to 2015. Patients with UIAs of which diameter ≥2.5 cm were studied. We reported the characteristics of patients and GIAs. Postoperative major complications were observed, and patient functional status were assessed with the modified Rankin Scale (mRS) at discharge and at the last follow-up. Twenty-one patients with unruptured GIAs were analysed, of whom 12 patients were treated by clipping, whereas 9 patients with unclippable aneurysms were treated by trapping or parent vessel occlusion. Fourteen aneurysms were saccular, and 7 were fusiform or serpentine. The mean aneurysm size was 3.7 ± 1.5 cm. After surgery, major complications were observed in 13 of the 21 (61.9%) patients. One (4.8%) patient died during hospital. After a mean 5.2-year follow-up, 9 (75.0%) patients treated by clipping and 7 (77.8%) treated by non-clipping experienced a good outcome (mRS ≤2). We found no significant difference in both postoperative complications and long-term outcome between clipping and non-clipping group. Favorable prognosis can be obtained in most patients with unruptured GIAs treated by appropriate microsurgical modality.

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

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.

Adipocyte fatty acid–binding protein (FABP4) played critical roles in metabolic syndrome, inflammatory responses and cardiovascular diseases. It aimed to investigate the associations of serum FABP4 levels with early stroke recurrence. This study included the 206 acute ischemic stroke patients hospitalized in our institution. Stroke recurrence events were assessed at the 3-month follow-up. The median of FABP level was 22.6 (IQR, 17.9-31.6) ng/mL in patients with stroke recurrence (N=36), which was higher than in patients without stroke recurrence [16.9 (IQR, 11.8-21.4) ng/mL] (P

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.

Baseline hematoma volume (HV) and hematoma growth (HG) affect the prognosis of spontaneous intracranial hematoma (ICH), but there is still a lack of evidence on the effects of aspirin (acetylsalicylic acid, ASA) on HV and HG in patients with severe ICH. This study retrospectively analyzed patients with severe ICH who met the inclusion and exclusion criterias 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 group according to ASA usage, and the effects of prior ASA on HV and HG were evaluated respectively. And possible risk factors for HG were screened. Totally, 221 patients with severe ICH were consecutively enrolled into this study. There were 72 (32.58%) patients in ASA group and 149 patients (67.42%) in nASA group. Although the baseline HV of the nASA group was significantly higher than that of the ASA group (45.51±29.76 VS 32.67±25.85, p=0.001), after adjusting for confounding factors, the prior ASA did not significantly affect the baseline HV (p = 0.057). Similarly, although the incidence of HG in nASA group was higher than that in ASA group (36.2% VS 25.0%, p = 0.095), ASA did not significantly affect the occurrence of HG (p =0.057). In addition, we found that admission high blood pressure and GCS were risk factors for HG. Prior ASA does not increase the baseline HV and the incidence of HG in severe ICH patients. In addition, admission high blood pressure and GCS were risk factors for HG.

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.

Subarachnoid hemorrhage (SAH) is a life-threatening neurological disease. Recently, inflammatory factors have been confirmed to be responsible for the brain damage associated with SAH. Therefore, studying the post-SAH inflammatory reaction may clarify the mechanism of SAH. Mitogen and stress-activated protein kinase 1 (MSK1) causes the phosphorylation of NF-κB and regulates the activity of pro-inflammatory transcription factors. The present study aimed to identify the potential role of MSK1 in inflammation and brain damage development following SAH. A cisterna magna blood injection model was established in Sprague-Dawley rats. Hematoxylin and eosin staining, reverse transcription-quantitative polymerase chain reaction assays and double immunofluorescence staining were used to analyze the role of MSK1, IL-1β and TNF-α in the inflammatory process after SAH. In a model of lipopolysaccharide-induced astrocyte inflammation, the effect of overexpressing MSK1 overexpression was analyzed by western blot analysis. The results demonstrated that MSK1 expression were negatively correlated with TNF-α and IL-1β expression levels, and reached peak levels 2 days after TNF-α and IL-1β. The double immunofluorescence staining results showed that the expression of MSK1 was in the same plane of view as TNF-α and IL-1β in the brain cortex. Furthermore, the in vitro studies indicated that the overexpression of MSK1 inhibited the expression of TNF-α and IL-1β following LPS challenge. These results imply that MSK1 may be involved in the inflammatory reaction following SAH, and may potentially serve as a negative regulator of inflammation.

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 ...

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. 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. 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). 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.

Oncology detection technology is significant for the early detection of tumors. The current study reports a new method that uses folate receptor (FR) as circulating tumor cells (CTCs) marker and only folate modified T30 as a probe. This method also uses dual-enzyme assisted amplification strategy for homogeneous fluorescence as well as two-dimensional visual (color and distance) detection of SMMC-7721 liver cancer cells from clinical blood samples. This work was based on the steric hindrance caused by binding between FR and folate to regulate cleavage of folate-T30 by exonuclease I (Exo I) and to inhibit subsequent polymerization and extension reaction of the cleavage product by terminal deoxynucleotidyl transferase (TdT). It explores the use of CdTe QDs to selectively identify Cu

Aim Luciferase immunoprecipitation (LIPS) assays show good sensitivity and specificity in testing islet specific autoantibodies for diagnosis of type 1 diabetes (T1D). However, there are currently no LIPS assays available for detecting proinsulin/insulin autoantibody (IAA) previously. We here developed a LIPS assay to measure IAA using nano luciferase (NanoLuc)-proinsulin fusion protein. Methods The NanoLuc-proinsulin fusion protein expression plasmid was constructed and transfected to COS1 cells. Expression and binding specificity to IAA of the fusion protein were validated. A LIPS assay using the NL-proinsulin fusion protein was developed and compared to radioimmunoassay (RIPA) in testing sera from 50 healthy controls and 34 T1D patients. Results The fusion protein was correctly expressed in transfected COS1 cells. Both NANOLUC activity and proinsulin were detected in the medium of transfected COS1 cells. Fusion protein bound to monoclonal anti insulin antibody and sera from T1D patients or NOD mice, these bindings were inhibited by recombinant human insulin. The LIPS assay using the fusion protein showed sensitivity of 47.1% and specificity of 98.0%. Further analysis supported correlation between the IAA indexes of all the T1D samples detected by LIPS assay and radioimmunoassay (RIPA, R2 = 0.6132, p Conclusions The NanoLuc-proinsulin fusion protein based LIPS has the potential to detect IAA for diagnosis of T1D.