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Xiao Shen,1 Jin-Xing Zhang,1 Jin Liu,2 Sheng Liu,1 Hai-Bin Shi,1 Yuan Cheng,3 Qing-Qiao Zhang,4 Guo-Wen Yin,5 Qing-Quan Zu1 1Department of Interventional Radiology, The First Affiliated Hospital with Nanjing Medical University, Nanjing, 210029, People’s Republic of China; 2Department of Clinical Medicine Research Institution, The First Affiliated Hospital with Nanjing Medical University, Nanjing, 210029, People’s Republic of China; 3Department of Medical Oncology, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, 210002, People’s Republic of China; 4Department of Interventional Radiology and Vascular Surgery, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, 221006, People’s Republic of China; 5Department of Interventional Radiology, The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, 210009, People’s Republic of ChinaCorrespondence: Qing-Quan Zu, Department of Interventional Radiology, The First Affiliated Hospital with Nanjing Medical University, No. 300, Guangzhou Road, Nanjing, 210029, People’s Republic of China, Tel +86-13913807470, Fax +86-25-83724440, Email zuqingquan@njmu.edu.cnPurpose: Transarterial chemoembolization (TACE), when used in combination with immunotherapy and antiangiogenic therapy, has been shown to have synergistic anticancer effects. The aim of this study was to further assess the efficacy and safety of TACE combined with atezolizumab and bevacizumab in the treatment of unresectable hepatocellular carcinoma (HCC) in the real world.Methods: Between August 2021 and September 2023, clinical information was collected from consecutive HCC patients who received treatment via TACE-Atezo/Bev at four tertiary institutions. This study evaluated the objective response rate (ORR), overall survival (OS), and progression-free survival (PFS) as outcomes. Predictors for OS and PFS were also analyzed. Treatment-related adverse events (TRAEs) were recorded and assessed.Results: Ninety-two patients were enrolled in this study, with a median follow-up duration of 14.1 months. The ORRs based on the modified Response Evaluation Criteria in Solid Tumors (RECIST) and RECIST 1.1 criteria were 54.3% and 41.3%, respectively. The median OS and PFS of the patients were 15.9 months [95% confidence interval (CI), 14.5– 17.2 months] and 9.1 months (95% CI, 7.4– 10.8 months), respectively. Multivariate analyses revealed that the Eastern Cooperative Oncology Group score and neutrophil‒lymphocyte ratio were independent risk factors for OS, whereas tumor size and extrahepatic metastasis were independent risk factors for PFS. Grade 3/4 TRAEs occurred in 16.3% (15/92) of the patients and were controlled conservatively.Conclusion: The combination of Atezo/Bev with TACE demonstrated acceptable synergistic therapeutic effects and manageable safety profiles in patients with unresectable HCC.Keywords: atezolizumab, bevacizumab, efficacy, hepatocellular carcinoma, transarterial chemoembolization

Shang-Yu Lu,1,* Han-Yao Sun,1,* Yan Zhou,2 Xi Luo,3 Sheng Liu,1 Wei-Zhong Zhou,1 Hai-Bin Shi,1 Wei Yang,1 Wei Tian1 1Department of Interventional Radiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, People’s Republic of China; 2Department of Radiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, People’s Republic of China; 3The First Affiliated Hospital of Soochow University, Suzhou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Wei Yang; Wei Tian, The First Affiliated Hospital of Nanjing Medical University, No. 300, Guangzhou Road, Nanjing, 210029, People’s Republic of China, Tel +86-18705164897 ; +86-13770615508, Email youngwei1988@163.com; tianwei@jsph.org.cnPurpose: Hepatocellular carcinoma (HCC) represents a significant global health problem, requiring precise prognostic tools for optimal treatment stratification. This study aimed to develop a new risk prediction score, called AD score, based on the serum markers alpha-fetoprotein (AFP) and des-γ-carboxy prothrombin (DCP), to offer an objective and accurate preoperative assessment of HCC in patients undergoing transarterial chemoembolization (TACE).Patients and Methods: This was a retrospective study that included 295 HCC patients who were subjected to TACE (training set, n=147; testing set, n=148). Serum AFP and DCP levels were log-transformed to construct the AD score. Multivariate Cox regression analysis on cirrhosis subgroups validated the objectivity of the model. Performance comparison of established models (Child Pugh, BCLC, ALBI, Up-to-seven, Six-and-twelve, Four and seven, HAP score, mHAP-II, FAIL-T score), was assessed through time-dependent receiver operating characteristic (ROC) curves and risk stratification.Results: The AD score, incorporating lgAFP and lgDCP, demonstrated superior predictive accuracy than the existing models. Time-dependent ROC curve revealed the consistent superiority of the AD score over a 5-year period. The risk stratification into low, intermediate, and high group based on the AD score showed a significant survival difference in both training and testing set.Conclusion: For HCC patients undergoing TACE, the AD score serves as an objective and straightforward prognostic tool, enhancing predictive accuracy and showcasing its clinical utility. It demonstrates potential significance as a crucial addition to preoperative risk assessment for TACE.Keywords: hepatocellular carcinoma, transarterial chemoembolization, prognostic model, risk assessment, AD score

Yu-Xing Chen,1,* Jin-Xing Zhang,1,* Chun-Gao Zhou,1 Jin Liu,2 Sheng Liu,1 Hai-Bin Shi,1 Qing-Quan Zu1 1Department of Interventional Radiology, The First Affiliated Hospital with Nanjing Medical University, Nanjing, 210029, People’s Republic of China; 2Department of Clinical Medicine Research Institution, The First Affiliated Hospital with Nanjing Medical University, Nanjing, 210029, People’s Republic of China*These authors contributed equally to this workCorrespondence: Qing-Quan Zu, Department of Interventional Radiology, The First Affiliated Hospital with Nanjing Medical University, No. 300 Guangzhou Road, Nanjing, 210029, People’s Republic of China, Tel +86-25-68306316 ; +86-13913807470, Fax +86-25-83724440, Email zuqingquan@njmu.edu.cnBackground: Combination of angiogenesis inhibitor may achieve better therapeutic synergistic efficacy, considering of tumor hypoxia and promoted angiogenesis after transarterial chemoembolization (TACE). This study aimed to compare the safety and efficacy of TACE plus lenvatinib (TACE-lenvatinib) with TACE alone for patients with unresectable hepatocellular carcinoma (HCC).Methods: Between June 2019 and September 2021, a total of 215 patients diagnosed with unresectable HCC were retrospectively reviewed, including 53 patients who received TACE-lenvatinib and 162 patients who received TACE alone. The patient selection bias between the TACE-lenvatinib group and the TACE group was balanced by propensity score matching analysis at a 1:2 ratio. Progression-free survival (PFS), overall survival (OS) and tumor response were evaluated in the two groups.Results: After propensity score matching analysis, 34 patients receiving TACE-lenvatinib and 68 patients receiving TACE alone were enrolled. The median PFS and OS times in the TACE-lenvatinib group were significantly greater than those in the TACE group (PFS: 8.3 months vs 4.6 months, P = 0.008; OS: 27.7 months vs 18.4 months, P = 0.043). The objective response rate (ORR) in the TACE-lenvatinib group was higher than that in the TACE alone group (64.1% vs 36.5%, P = 0.002). Univariate and multivariate analyses revealed that TACE-lenvatinib treatment was an independent favorable prognostic factor for both PFS and OS.Conclusion: For unresectable HCC patients, the TACE-lenvatinib appeared superior to TACE alone regarding tumor control, PFS, and OS. However, considering the limitations of this study, these results should be interpreted as preliminary and warrant further confirmation.Keywords: carcinoma, hepatocellular, chemoembolization, therapeutic, lenvatinib, survival analysis, propensity score

Jin-Xing Zhang,1,* Pei Chen,2,* Sheng Liu,1 Qing-Quan Zu,1 Hai-Bin Shi,1 Chun-Gao Zhou1 1Department of Interventional Radiology, The First Affiliated Hospital with Nanjing Medical University, Nanjing, 210029, People’s Republic of China; 2Department of Basic Medicine, Jiangsu College of Nursing, Huai’an, 223005, People’s Republic of China*These authors contributed equally to this workCorrespondence: Hai-Bin Shi; Chun-Gao Zhou, Department of Interventional Radiology, The First Affiliated Hospital with Nanjing Medical University, No. 300 Guangzhou Road, Nanjing, 210029, People’s Republic of China, Tel +86-25-68306316 ; +86-13770598792, Fax +86-25-83724440, Email shihb@njmu.edu.cn; 1062874094@qq.comBackground: The clinical outcomes of hepatocellular carcinoma (HCC) patients who receive transarterial chemoembolization (TACE) and immunotherapy are not well characterized. The present study evaluates the safety and efficacy of TACE in combination with immune checkpoint inhibitor treatment for unresectable HCC.Methods: A retrospective analysis of 34 HCC patients who received TACE and treatment with the immune checkpoint inhibitor (ICI), Camrelizumab, between July 2019 and May 2021, was performed. This included 21 patients who developed progressive disease and eight who remained stable after several sessions of TACE, along with five patients who were initially diagnosed with advanced HCC. Adverse events (AEs), objective response rate (ORR) according to modified response evaluation criteria in solid tumors, progression-free survival (PFS), and overall survival (OS) were evaluated.Results: The median follow-up from ICI initiation was 10.6 months (range: 2.4– 25.0 months). Grade I/II and grade III/IV AEs from ICI treatment occurred in 20 (58.8%) and 2 patients (5.9%), respectively. Two to three months after ICI therapy, the ORR was 35.3% (12/34) and the median PFS and OS was 6.1 months (range: 1.1– 19.3 months) and 13.3 months (range: 2.4– 25.0 months), respectively.Conclusion: TACE in combination with ICI could be a promising treatment approach for unresectable HCC patients.Keywords: efficacy, hepatocellular carcinoma, immune checkpoint inhibition, safety, transarterial chemoembolization

This study was designed to evaluate the efficacy and safety of percutaneous mechanical thrombectomy (PMT) for acute massive pulmonary embolism (PE). Fourteen patients (8 men, 6 women) with a mean age of 55.4 (range, 38-71) years with acute massive PE were initially diagnosed by computed tomography (CT) and confirmed by pulmonary angiography. All patients presented with acute PE symptoms and hemodynamic compromise. Each patient was treated with Straub Rotarex thrombectomy device and five patients received additional thrombolysis. Technique success and clinical improvement were achieved in all patients without major complications. The mean pulmonary artery pressure (PAP) decreased from 37.6 ± 6.6 to 29 ± 6.4 mmHg (P < 0.01) after PMT. Partial arterial pressures of O(2) (PaO(2)) increased from 61.1 ± 9.2 to 88 ± 5.1 mmHg (P < 0.01). The Miller index was 0.67 ± 0.11 and 0.37 ± 0.13 (P < 0.01), respectively, before and after PMT (P < 0.01). Eleven patients had no recurrence of PE on a mean follow-up of 28.3 months, whereas the other three patients were lost to follow-up. The preliminary experience in our series suggests that the Straub Rotarex thrombectomy device, which has been utilized in peripheral arteries, also is useful for the treatment of acute massive PE. [ABSTRACT FROM AUTHOR]

Rationale and Objectives: Endovascular recanalization has been attempted in patients with symptomatic chronic intracranial large artery occlusion (CILAO), however, the heterogeneity of recanalization outcomes present challenges for the clinical application., Objective: To determine the radiological features on high-resolution MR imaging (HR-MRI) for predicting successful recanalization of symptomatic CILAO., Methods: Seventy-three patients with symptomatic CILAO who underwent endovascular recanalization at our center were retrospectively analyzed. Patients' clinical information, HR-MRI characteristics, procedural results, and outcomes were recorded. Factors related to successful recanalization were analyzed by univariate and multivariate analyses., Results: Technical success was achieved in 61 (83.6%) patients, with a complication rate of 13.7% (10/73). Based on multivariate analysis, responsible occluded artery (middle cerebral artery (MCA) trunk versus intracranial internal carotid artery (ICA), P = 0.004; MCA trunk versus intracranial vertebrobasilar artery (VBA), P = 0.010), occlusion with residual lumen (P = 0.036), occlusion with marked plaque enhancement (P = 0.011), and shorter occlusion length (≤10.2 mm versus >10.2 mm, P = 0.008) were identified as independent positive predictors of successful recanalization. Patients were assigned score points according to the coefficients of the prediction model, and the technical success rates were 50.0%, 83.3%, 95.5%, and 100% in patients with score ≤ 2, 3, 4, and ≥ 5 points, respectively., Conclusions: The HR-MRI modality may be valuable in identifying candidates for endovascular recanalization of symptomatic CILAO. MCA trunk occlusion, occlusion with residual lumen, occlusion with marked plaque enhancement and shorter occlusion length on HR-MRI appear to be significantly associated with the success of recanalization., 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 © 2024 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.)

Background: Accurately forecasting early neurological deterioration of ischemic origin (END i ) following medical management may aid in identifying candidates for thrombectomy. We aimed to develop and validate a nomogram to predict END i in patients with mild large and medium vessel occlusion stroke intended for medical management., Methods: Two hundred and forty-eight patients were enrolled (173 and 75 randomised into training and validation cohorts). The risk factors were identified using logistic regression analyses. A nomogram was constructed based on the risk factors identified. The discrimination, calibration, and clinical practicability of the nomogram were assessed using receiver operating characteristic curve (ROC) analysis, the Hosmer-Lemeshow test, and decision curve analysis (DCA), respectively., Results: END i was detected in 44 (17.7%) patients. Four predictors were identified in the training cohort and entered into the nomogram including age, symptom fluctuation characteristics, presence of core infarct, and occlusion site. ROC analysis showed that the area under the curve was 0.930 (95% CI 0.884 to 0.976) and 0.889 (95% CI 0.808 to 0.970) in the training and validation cohorts, respectively. The Hosmer-Lemeshow test yielded a mean absolute error of 0.025 and 0.038, respectively, for the two cohorts. The DCA showed that the nomogram model had superior practicality and accuracy across the majority of the threshold probabilities., Conclusion: The proposed nomogram showed a favourable predictive performance for END i in patients with mild large and medium vessel occlusion stroke intended for medical management. For such patients, immediate thrombectomy or at least intensive medical monitoring may be reasonable to avoid delays in rescue thrombectomy., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: This study aimed to compare the survival outcomes of transarterial chemoembolization (TACE) between patients with early recurrent hepatocellular carcinoma (rHCC) after hepatic resection, stratified by cytokeratin (CK) 19 expression., Methods: A retrospective analysis was conducted on 63 patients with early rHCC after hepatic resection who underwent TACE between January 2017 and December 2021. Patients were divided into two groups based on CK19 expression: CK19-negative (n=31) and CK19-positive (n=32). Overall survival (OS) and progression-free survival (PFS) were compared between the two groups using the Kaplan-Meier method and log-rank test. Cox regression analysis was performed to identify independent risk factors for OS and PFS., Results: The CK19-negative group demonstrated a significantly longer median OS compared to the CK19-positive group (635 days vs. 432 days, p=0.013). Similarly, the CK19-negative group had a longer median PFS than the CK19-positive group (291 days vs. 117 days, p=0.014). Multivariate Cox analysis identified Child-Pugh A grade, CK19-negative expression, and increased TACE sessions as protective factors for OS. No severe TACE-related adverse events were observed., Conclusion: In patients with early rHCC after hepatic resection, those with CK19-positive expression had poorer survival outcomes following TACE compared to CK19-negative patients. These findings suggest the need for additional therapies to improve survival in CK19-positive individuals., (© 2024. The Author(s).)

Background and Purpose: It remains unclear whether the combination of endovascular treatment (EVT) with intravenous thrombolysis (IVT) results in a more favorable functional outcome than EVT alone in managing cases of acute ischemic stroke (AIS) caused by basilar artery occlusion (BAO). Thus, this study aimed to compare the outcomes of two approaches-direct EVT (DEVT) and bridging therapy (IVT plus EVT)-in acute BAO patients presenting within 4.5 hours of stroke onset., Materials and Methods: This multicenter retrospective cohort study included 153 acute BAO patients presenting within 4.5 hours of stroke onset. Of these patients, 65 (42.5%) and 88 (57.5%) underwent DEVT and bridging therapy, respectively. The primary outcome was defined as good functional outcome (modified Rankin Scale, 0-3) at 90 days. Additionally, pre-operative clinical features, thrombectomy attempts, successful reperfusion rates, incidences of symptomatic intracranial hemorrhage (sICH), and mortality were compared between the two groups., Results: At 90 days, the rate of good functional outcome was comparable between the DEVT (44.6%) and bridging-therapy (39.8%) groups (adjusted odds ratio [aOR], 1.12; 95% confidence interval [CI], 0.55-2.31; p = 0.753). The bridging-therapy group exhibited a lower percentage of patients requiring ≥ 3 attempts of stent retrieval (aOR, 0.39; 95% CI, 0.16-0.93; p = 0.034). Pre-operative clinical features, rate of successful reperfusion, sICH, and mortality were similar between the two groups., Conclusions: In patients with BAO-induced AIS, DEVT demonstrates a comparable functional outcome to bridging therapy within 4.5 hours of symptom onset, but IVT reduces the number of thrombectomy attempts., Abbreviations: AIS, acute ischemic stroke; LVO, large-vessel occlusion; EVT, endovascular treatment; IVT, intravenous thrombolysis; BAO, basilar artery occlusion; DEVT, direct endovascular treatment; sICH, symptomatic intracranial hemorrhage; RCT, randomized controlled trial; IRIS, Improving Reperfusion Strategies in Ischemic Stroke; TOAST, Trial of ORG 10172 in Acute Stroke Treatment; mTICI, modified thrombolysis in cerebral infarction; SD, standard deviation; IQR, interquartile range; ICAS, intracranial atherosclerotic stenosis., Competing Interests: The authors declare no conflicts of interest related to the content of this article, (© 2024 by American Journal of Neuroradiology.)

Hyperbilirubinemia (HB) is a key risk factor for hearing loss in neonates, particularly premature infants. Here we report that bilirubin (BIL)-dependent cell death in auditory brainstem of neonatal mice of both sexes is significantly attenuated by ZD7288, a blocker for hyperpolarization-activated cyclic nucleotide-gated (HCN) channel mediated current (I h ), or by genetic deletion of HCN1. GABAergic inhibitory interneurons predominantly express HCN1, on which BIL selectively acts to increase their intrinsic excitability and mortality by enhancing HCN1 activity and Ca 2+ -dependent membrane targeting. Chronic BIL elevation in neonatal mice in vivo increases the fraction of spontaneously active interneurons and their firing frequency, I h and death, compromising audition at young adult stage in HCN1 +/+ , but not in HCN1 -/- genotype. We conclude that HB preferentially targets HCN1 to injure inhibitory interneurons, fueling a feedforward loop in which lessening inhibition cascades hyperexcitability, Ca 2+ overload, neuronal death and auditory impairments. These findings rationalize HCN1 as a potential target for managing HB encephalopathy. Significance Statement This study demonstrated that bilirubin preferentially targets GABAergic interneurons where it facilitates not only gating of HCN1 channels but also targeting of intracellular HCN1 to plasma membrane in calcium-dependent manner, resulting in neuronal hyperexcitability, injury and sensory dysfunction. These findings implicate HCN1 channel not only as a potential driver for auditory abnormalities in neonatal patients with bilirubin encephalopathy, but also potential intervention target for clinical management of neurological impairments associated with severe jaundice. Selective vulnerability of interneurons to neurotoxicity may be of general significance for understanding other forms of brain injury., (Copyright © 2024 the authors.)

Background and Purpose: Malnutrition is associated with poor outcomes in different diseases. Our aim was to investigate whether measures of malnutrition could be used to predict 90-day outcomes in patients with vertebrobasilar artery occlusion (VBAO) undergoing endovascular treatment (EVT)., Methods: We retrospectively analyzed patients with VBAO who received EVT at three comprehensive stroke centers. Malnutrition was assessed using the controlling nutritional status (CONUT) score, geriatric nutritional risk index (GNRI), and prognostic nutritional index (PNI). Primary outcome was good functional outcome defined as modified Rankin Scale (mRS) 0-3 measured at 90 days., Results: A total of 285 patients were enrolled, of which 260 (91.22 %) met the requirements. According to the CONUT, GNRI, and PNI scores, the proportions of patients classified as moderately or severely malnourished were 7.3 %, 3.08 %, and 35 %, respectively. In the multivariate regression model after adjusting for potential confounders, malnutrition (severe risk versus normal nutritional status) was significantly associated with an increased risk of poor prognosis for CONUT scores (adjusted odds ratio [OR]14.91, 95 %CI, 1.69 - 131.71; P = 0.015), GNRI scores (adjusted [OR] 10.67, 1.17 - 96.93; P = 0.036) and PNI scores (adjusted [OR] 4.61, 2.28 - 9.31; P < 0.001). Similar results were obtained when malnutrition scores were analyzed as continuous variables. Adding the 3 malnutrition measures to the risk reclassification that included traditional risk factors significantly improved the predictive value of 3-month poor prognosis., Conclusions: Our study showed that malnutrition may be associated with poor prognosis within 3 months of EVT in patients with VBAO., Competing Interests: Declaration of competing interest All authors disclosed no relevant relationships., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: To investigate the association between perfusion deficit, vessel wall characteristics, and risk of recurrent ischemic events in medically treated patients with chronic symptomatic anterior circulation large vessel occlusion., Methods: We retrospectively reviewed chronic symptomatic patients due to anterior circulation large vessel occlusion in our center. All patients received multiparametric magnetic resonance imaging (including perfusion-weighted imaging and high-resolution vessel wall imaging) within 4 weeks to 3 months after symptom onset. The association between baseline clinical or imaging variables and recurrent ischemic events was assessed in bivariate models and multivariable logistic regression to identify independent predictors of recurrence., Results: Among 71 enrolled patients, 21.1% (15/71) patients had recurrent ischemic events (nine ischemic strokes and six transient ischemic attacks) during a 2-year follow-up. In bivariate models, hypertension, occlusion with hyperintense signals, the presence of intraluminal thrombus, Tmax >4 s volume, Tmax >6 s volume, Tmax >8 s volume, and Tmax >10 s volume were associated with recurrence (all p  < 0.05). In multivariate analysis, hypertension ( p  = 0.039, OR 10.057 (95% CI, 1.123-90.048)), higher deficit volume of Tmax >4 s ( p  = 0.011, OR 1.012 (95% CI, 1.003-1.021)) and occlusion with hyperintense signal ( p  = 0.030, OR 6.732 (95% CI, 1.200-37.772)) were still independent predictors of recurrent ischemic events., Conclusions: Besides hypertension history, higher deficit volume of Tmax >4 s and occlusion with hyperintense signal determined using multiparametric MRI are strongly associated with risk for recurrent ischemic events in medically treated patients with chronic symptomatic anterior circulation large vessel occlusion. Future studies are needed to determine the utility of revascularization strategies in such high-risk patients., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Purpose: Not all patients benefit from transarterial chemoembolization (TACE) due to the heterogeneity of the tumour burden in intermediate-stage hepatocellular carcinoma (HCC). To compare the outcomes of transarterial chemoembolization (TACE) combined with molecular-targeted agents plus immune checkpoint inhibitors (TACE-MTAs-ICIs) with those of TACE for patients with unresectable hepatocellular carcinoma (uHCC) that were beyond the up-to-seven criteria., Patients and Methods: Between January 2019 and July 2022, 130 patients diagnosed with uHCC beyond the up-to-seven criteria were retrospectively identified, including 47 patients who received TACE-MTAs-ICIs and 83 patients who received TACE alone. The primary endpoints were overall survival (OS) and progression-free survival (PFS); the secondary endpoints included tumour response and adverse events (AEs)., Results: There were 43 matched patients. The median OS and PFS times in the TACE-MTAs-ICIs group were significantly longer than those in the TACE group (OS: 27.2 vs. 15.9 months, p  = 0.007; PFS: 15.4 months vs. 4.8 months, p  < 0.001). The objective response rate (ORR) in the TACE-MTAs-ICIs group was higher than that in the TACE group (65.1% vs. 37.2%, p  = 0.010). Reversible AEs (grade 3 or 4) occurred differently in TACE-MTAs-ICIs and TACE groups (83.7% vs. 51.2%, p  = 0.001). Univariate and multivariate analyses revealed that TACE-MTAs-ICIs treatment was an independent favourable prognostic factor for both PFS and OS ( p  < 0.001)., Conclusion: For uHCC patients beyond the up-to-seven criteria, TACE-MTAs-ICIs provided superior ORR and OS. Early combined TACE and systemic treatment should shift for patients who are beyond these criteria.

To evaluate the prognostic value of venous outflow (VO) profiles evaluated on multiphase CTA (mCTA) for the patients with acute ischemic stroke (AIS) after endovascular thrombectomy (EVT). We retrospectively collected 150 patients with AIS who underwent pre-treatment CT perfusion (CTP) evaluation and subsequent EVT from April 2018 to April 2022. Three-phases (peak arterial phase, peak venous phase, late venous phase) CTA was reconstructed from CTP raw data, and VO was evaluated on three-phases CTA, respectively. Favorable VO was regarded as a cortical vein opacification score of 3-6, and unfavorable VO as a score of 0-2. Good outcome was defined as modified Rankin Scale score of 0-2 at 90 days after EVT. Multivariate logistic regression analysis was performed to explore the predictors of good outcome. Prognostic value was assessed and compared using receiver operating characteristic (ROC) curves and Delong test. We found that good outcome was achieved in 85 (56.7%) patients. Among the mCTA-derived VO profiles, only favorable peak venous phase VO was found to be independently associated with good outcome (P < 0.001). After integrating favorable peak venous phase VO with lower post-treatment National Institute of Health Stroke Scale score at 24 hours, successful recanalization and favorable hypoperfusion intensity ratio, the predictive ability for a good outcome was significantly improved than before (area under the ROC curve; 0.947 vs 0.881; P = 0.002). This study supports that favorable peak venous VO profiles on mCTA might be a promising biomarker in predicting the good outcome in patients with AIS after EVT., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: To explore the microstate characteristics and underlying brain network activity of Ménière's disease (MD) patients based on high-density electroencephalography (EEG), elucidate the association between microstate dynamics and clinical manifestation, and explore the potential of EEG microstate features as future neurobiomarkers for MD., Methods: Thirty-two patients diagnosed with MD and 29 healthy controls (HC) matched for demographic characteristics were included in the study. Dysfunction and subjective symptom severity were assessed by neuropsychological questionnaires, pure tone audiometry, and vestibular function tests. Resting-state EEG recordings were obtained using a 256-channel EEG system, and the electric field topographies were clustered into four dominant microstate classes (A, B, C, and D). The dynamic parameters of each microstate were analyzed and utilized as input for a support vector machine (SVM) classifier to identify significant microstate signatures associated with MD. The clinical significance was further explored through Spearman correlation analysis., Results: MD patients exhibited an increased presence of microstate class C and a decreased frequency of transitions between microstate class A and B, as well as between class A and D. The transitions from microstate class A to C were also elevated. Further analysis revealed a positive correlation between equilibrium scores and the transitions from microstate class A to C under somatosensory challenging conditions. Conversely, transitions between class A and B were negatively correlated with vertigo symptoms. No significant correlations were detected between these characteristics and auditory test results or emotional scores. Utilizing the microstate features identified via sequential backward selection, the linear SVM classifier achieved a sensitivity of 86.21% and a specificity of 90.61% in distinguishing MD patients from HC., Conclusions: We identified several EEG microstate characteristics in MD patients that facilitate postural control yet exacerbate subjective symptoms, and effectively discriminate MD from HC. The microstate features may offer a new approach for optimizing cognitive compensation strategies and exploring potential neurobiological markers in MD., (© 2024 The Author(s). CNS Neuroscience & Therapeutics published by John Wiley & Sons Ltd.)

Introduction: Lipid metabolism dysfunction is widely involved in the pathological process of acute ischemic stroke (AIS). The coordination of lipid metabolism between neurons and astrocytes is of great significance. However, the full scope of lipid dynamic changes and the function of key lipids during AIS remain unknown. Hence, identifying lipid alterations and characterizing their key roles in AIS is of great importance., Methods: Untargeted and targeted lipidomic analyses were applied to profile lipid changes in the ischemic penumbra and peripheral blood of transient middle cerebral artery occlusion (tMCAO) mice as well as the peripheral blood of AIS patients. Infarct volume and neurological deficits were assessed after tMCAO. The cell viability and dendritic complexity of primary neurons were evaluated by CCK8 assay and Sholl analysis. Seahorse, MitoTracker Green, tetramethyl rhodamine methyl ester (TMRM), 2',7'-dichlorodihydrofluorescein diacetate (DCFH-DA) and MitoSOX were used as markers of mitochondrial health. Fluorescent and isotopic free fatty acid (FFA) pulse-chase assays were used to track FFA flux in astrocytes., Results: Long-chain acylcarnitines (LCACs) were the lipids with the most dramatic changes in the ischemic penumbra and peripheral blood of tMCAO mice. LCACs were significantly elevated on admission in AIS patients and associated with poor outcomes in AIS patients. Increasing LCACs through a bolus administration of palmitoylcarnitine amplified stroke injury, while decreasing LCACs by overexpressing carnitine palmitoyltransferase 2 (CPT2) ameliorated stroke injury. Palmitoylcarnitine aggravated astrocytic mitochondrial damage after OGD/R, while CPT2 overexpression in astrocytes ameliorated cocultured neuron viability. Further study revealed that astrocytes stimulated by OGD/R liberated FFAs from lipid droplets into mitochondria to form LCACs, resulting in mitochondrial damage and lowered astrocytic metabolic support and thereby aggravated neuronal damage., Conclusion: LCACs could accumulate and damage neurons by inducing astrocytic mitochondrial dysfunction in AIS. LCACs play a crucial role in the pathology of AIS and are novel promising diagnostic and prognostic biomarkers for AIS., 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 © 2024. Production and hosting by Elsevier B.V.)

Glutamate is traditionally viewed as the first messenger to activate NMDAR (N-methyl-D-aspartate receptor)-dependent cell death pathways in stroke 1,2 , but unsuccessful clinical trials with NMDAR antagonists implicate the engagement of other mechanisms 3-7 . Here we show that glutamate and its structural analogues, including NMDAR antagonist L-AP5 (also known as APV), robustly potentiate currents mediated by acid-sensing ion channels (ASICs) associated with acidosis-induced neurotoxicity in stroke 4 . Glutamate increases the affinity of ASICs for protons and their open probability, aggravating ischaemic neurotoxicity in both in vitro and in vivo models. Site-directed mutagenesis, structure-based modelling and functional assays reveal a bona fide glutamate-binding cavity in the extracellular domain of ASIC1a. Computational drug screening identified a small molecule, LK-2, that binds to this cavity and abolishes glutamate-dependent potentiation of ASIC currents but spares NMDARs. LK-2 reduces the infarct volume and improves sensorimotor recovery in a mouse model of ischaemic stroke, reminiscent of that seen in mice with Asic1a knockout or knockout of other cation channels 4-7 . We conclude that glutamate functions as a positive allosteric modulator for ASICs to exacerbate neurotoxicity, and preferential targeting of the glutamate-binding site on ASICs over that on NMDARs may be strategized for developing stroke therapeutics lacking the psychotic side effects of NMDAR antagonists., (© 2024. The Author(s).)

Microwave ablation (MWA) is recognized as a novel treatment modality that can kill tumor cells by heating the ions and polar molecules in these cells through high-speed rotation and friction. However, the size and location of the tumor affect the effective ablation range of microwave hyperthermia, resulting in residual tumor tissue and a high recurrence rate. Due to their tunable porous structure and high specific surface area, metal-organic frameworks (MOFs) can serve as microwave sensitizers, promoting microwave energy conversion owing to ion collisions in the porous structure of the MOFs. Moreover, iron-based compounds are known to possess peroxidase-like catalytic activity. Therefore, Fe-doped Cu bimetallic MOFs (FCMs) were prepared through a hydrothermal process. These FCM nanoparticles not only increased the efficiency of microwave-thermal energy conversion as microwave sensitizers but also promoted the generation of reactive oxygen species (ROS) by consuming glutathione (GSH) and promoted the Fenton reaction to enhance microwave dynamic therapy (MDT). The in vitro and in vivo results showed that the combination of MWA and MDT treatment effectively destroyed tumor tissues via microwave irradiation without inducing significant side effects on normal tissues. This study provides a new approach for the combined application of MOFs and microwave ablation, demonstrating excellent potential for future applications.

Purpose: To compare the efficacy of transarterial chemoembolization (TACE) combined with tyrosine kinase inhibitors (TKIs) plus immune checkpoint inhibitors (ICIs) (TACE-TKI-ICI) versus TKIs plus ICIs (TKI-ICI) for unresectable hepatocellular carcinoma (HCC) with first- or lower-order portal vein tumor thrombosis (PVTT)., Materials and Methods: A retrospective study was performed in HCC patients with first- or lower-order PVTT receiving TKIs (Lenvatinib or sorafenib) plus ICIs (camrelizumab, sintilimab, or atezolizumab) with or without TACE from four institutions between January 2019 and January 2022. Propensity score-based method was performed to minimize bias by confounding factors. Tumor response, progression-free survival (PFS), overall survival (OS), and adverse events (AEs) were evaluated and compared between the two groups., Results: After inverse probability of treatment weighting, two balanced pseudopopulations were created: 106 patients in the TACE-TKI-ICI group and 109 patients in the TKI-ICI group. The objective response rate was higher in the TACE-TKI-ICI group (50.9% vs. 28.4%, P < 0.001). The median PFS and OS were significantly longer in the TACE-TKI-ICI group than in the TKI-ICI group (PFS: 9.1 vs. 5.0 months, P = 0.005; OS: 19.1 vs. 12.7 months, P = 0.002). In Cox regression, TACE-TKI-ICI treatment was an independent predictor of favorable OS. Treatment-related grade 3/4 AEs were comparable between the two groups (22.6% vs. 17.9%, P = 0.437)., Conclusion: TACE-TKI-ICI therapy contributed to better tumor control, PFS and OS than TKI-ICI therapy in unresectable HCC patients with first- or lower-order PVTT., (© 2024. Springer Science+Business Media, LLC, part of Springer Nature and the Cardiovascular and Interventional Radiological Society of Europe (CIRSE).)

Purpose: Combining angiogenesis inhibitors may enhance therapeutic efficacy synergistically after TACE refractoriness. The purpose of this study was to compare the outcomes of transarterial chemoembolization (TACE) plus a tyrosine kinase inhibitor (TACE-TKI) with TKI only for patients with TACE-refractory hepatocellular carcinoma (HCC)., Methods: From January 2019 to March 2022, 101 HCC patients confirmed with TACE-refractory were retrospectively reviewed in the study. Progression-free survival (PFS), overall survival (OS), tumor response, and adverse events (AEs) were evaluated between groups., Results: Fifty-two patients undergoing TACE-TKI, while 32 patients receiving TKI alone were included. The objective response rate (ORR) was higher in the TACE-TKI group compared with the TKI group (55.8% vs. 25.0%, P = 0.006). The median PFS in the TACE-TKI group was significantly longer than that in the TKI group (7.6 months vs. 4.9 months, P = 0.018). The median OS was non reach to statistical longer than that in the TKI alone group (19.5 months vs. 17.7 months, P = 0.055). Subgroup analysis showed that TACE-TKI treatment resulted in a significantly longer median PFS and OS for Barcelona Clinic Liver Cancer (BCLC) stage B patients (PFS 11.8 months vs. 5.1 months, P = 0.017; OS 30.3 months vs. 19.4 months, P = 0.022)., Conclusion: For patients with TACE-refractory HCC, TACE-TKI appeared to be superior to TKI monotherapy with regard to tumor control and PFS. Furthermore, for the BCLC stage B subgroup, TACE-TKI therapy was superior to TKI monotherapy in both OS and PFS., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: The role of transarterial chemoembolization (TACE) in the treatment of advanced hepatocellular carcinoma (HCC) is unconfirmed. This study aimed to assess the efficacy and safety of immune checkpoint inhibitors (ICIs) plus anti-vascular endothelial growth factor (anti-VEGF) antibody/tyrosine kinase inhibitors (TKIs) with or without TACE as first-line treatment for advanced HCC., Methods: This nationwide, multicenter, retrospective cohort study included advanced HCC patients receiving either TACE with ICIs plus anti-VEGF antibody/TKIs (TACE-ICI-VEGF) or only ICIs plus anti-VEGF antibody/TKIs (ICI-VEGF) from January 2018 to December 2022. The study design followed the target trial emulation framework with stabilized inverse probability of treatment weighting (sIPTW) to minimize biases. The primary outcome was overall survival (OS). Secondary outcomes included progression-free survival (PFS), objective response rate (ORR), and safety. The study is registered with ClinicalTrials.gov, NCT05332821., Findings: Among 1244 patients included in the analysis, 802 (64.5%) patients received TACE-ICI-VEGF treatment, and 442 (35.5%) patients received ICI-VEGF treatment. The median follow-up time was 21.1 months and 20.6 months, respectively. Post-application of sIPTW, baseline characteristics were well-balanced between the two groups. TACE-ICI-VEGF group exhibited a significantly improved median OS (22.6 months [95% CI: 21.2-23.9] vs 15.9 months [14.9-17.8]; P < 0.0001; adjusted hazard ratio [aHR] 0.63 [95% CI: 0.53-0.75]). Median PFS was also longer in TACE-ICI-VEGF group (9.9 months [9.1-10.6] vs 7.4 months [6.7-8.5]; P < 0.0001; aHR 0.74 [0.65-0.85]) per Response Evaluation Criteria in Solid Tumours (RECIST) version 1.1. A higher ORR was observed in TACE-ICI-VEGF group, by either RECIST v1.1 or modified RECIST (41.2% vs 22.9%, P < 0.0001; 47.3% vs 29.7%, P < 0.0001). Grade ≥3 adverse events occurred in 178 patients (22.2%) in TACE-ICI-VEGF group and 80 patients (18.1%) in ICI-VEGF group., Interpretation: This multicenter study supports the use of TACE combined with ICIs and anti-VEGF antibody/TKIs as first-line treatment for advanced HCC, demonstrating an acceptable safety profile., Funding: National Natural Science Foundation of China, National Key Research and Development Program of China, Jiangsu Provincial Medical Innovation Center, Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, and Nanjing Life Health Science and Technology Project., Competing Interests: We declare no competing interests., (© 2024 Published by Elsevier Ltd.)

Background: Gadolinium (Gd)-based contrast agents (GBCAs) have been widely used for acute ischemic stroke (AIS) patients. GBCAs or AIS alone may cause the adverse effects on kidney tissue, respectively. However, whether GBCAs and AIS would generate a synergistic negative effect remains undefined., Purpose: To evaluate synergistic negative effects of AIS and GBCAs on renal tissues in a mouse model of AIS, and to compare the differences of these negative effects between linear and macrocyclic GBCAs., Study Type: Animal study., Animal Model: Seventy-two healthy mice underwent transient middle cerebral artery occlusion (tMCAO) and sham operation to establish AIS and sham model (N = 36/model). 5.0 mmol/kg GBCAs (gadopentetate or gadobutrol) or 250 μL saline were performed at 4.5 hours and 1 day after model establishing (N = 12/group)., Assessment: Inductively coupled plasma mass spectrometry (ICP-MS) was performed to detect Gd concentrations. Serum biochemical analyzer was performed to measure the serum creatinine (Scr), uric acid (UA), and blood urea nitrogen (BUN). Pathological staining was performed to observe tubular injury, cell apoptosis, mesangial hyperplasia, and interstitial fibrosis., Statistical Tests: Two-way analysis of variances with post hoc Sidak's tests and independent-samples t-tests were performed. A P-value <0.05 was considered statistically significant., Results: AIS groups showed higher Gd concentration than sham group on day 1 p.i. regardless of gadopentetate or gadobutrol used. Increased total Gd concentration was also found in AIS + gadopentetate group compared with the sham group on day 28 p.i. Significantly higher rates for renal dysfunction, higher tubular injury scores, and higher numbers of apoptotic cells on days 1 or 28 p.i. were found for AIS mice injected with GBCA. AIS + gadopentetate group displayed more severe renal damage than the AIS + gadobutrol group., Data Conclusion: AIS and GBCAs may cause increased total Gd accumulation and nephrotoxicity in a mouse, especially linear GBCAs were used., Level of Evidence: 1 TECHNICAL EFFICACY: Stage 4., (© 2023 International Society for Magnetic Resonance in Medicine.)

Background and Study Aims: Esophageal restenosis is a serious complication after esophageal stent placement, which influences the clinical prognosis of stent implantation and the patient's quality of life. TGF-β1/Smads signaling pathway plays an important role in the development of the eosinophilic esophagitis and scar repair after skin trauma. However, the role of TGF-β1/Smads in the development of esophageal restenosis after esophageal stent placement remains unknown. Our study aimed to investigate whether TGF-β1/Smads plays an important role in the development of esophageal restenosis after esophageal stent, and whether the exogenous TGF-β1 inhibitor supplement could ameliorate the esophageal restenosis after esophageal stent., Material and Methods: We established the model of esophageal restenosis after esophageal stenting in rats, and determined the expression levels of TGF-β1/Smads signaling pathway and the relevant markers of fibroblast activation by immunochemistry (IHC), Western Blot and real time qPCR. Those all the indicators were also determined in esophageal fibroblast when exposed to rhTGF-β1 with or without TGF-β1 inhibitor P144., Results: The serum level of IL-1β and TNFα were significantly increased in stent implantation group compared to blank control group, and obviously ameliorated when treated with P144. The TGF-β1/Smads signaling pathway and the relevant markers of fibroblast activation were significantly increased in stent implantation group compared to blank control group, and obviously ameliorated when treated with P144. Those all the indicators were significantly increased when exposed to rhTGF-β1, and obviously decreased when treated with P144., Conclusions: TGF-β1 Inhibitor P144 could protect against benign restenosis after esophageal stenting by down-regulating the expression levels of relevant markers of fibroblast activation through TGF-β1/Smads signaling pathway inhibition, and may be used as a novel therapy for benign restenosis after esophageal stenting., Competing Interests: Declaration of competing interests 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 © 2024 Pan-Arab Association of Gastroenterology. Published by Elsevier B.V. All rights reserved.)

RATIONALE AND OBJECTIVES: As an effective locoregional therapy, transarterial chemoembolization (TACE) can induce vascular endothelial growth factor and PD-1/PDL-1 upregulation, accompanied by a reduction in tumor burden. The present study aimed to compare the efficacy of TACE combined with tyrosine kinase inhibitors (TKIs) plus immune checkpoint inhibitors (ICIs) (TACE-TKI-ICIs) versus TKIs plus ICIs (TKI-ICIs) in patients with unresectable hepatocellular carcinoma (HCC)., Materials and Methods: The clinical data of 198 patients diagnosed with unresectable HCC who received a TKI (lenvatinib or sorafenib) plus an ICI (sintilimab or camrelizumab) with or without TACE were retrospectively reviewed between October 2019 and April 2022. Baseline characteristics of the TACE-TKI-ICI group and the TKI-ICI group were matched by propensity score matching in a 1:1 ratio. The tumor response, progression-free survival (PFS), and overall survival (OS) were evaluated and compared between the two groups., Results: After matching, 54 patients were enrolled in each group. The objective response rate (ORR) and disease control rate (DCR) were higher in the TACE-TKI-ICI group (ORR: 63.0% vs. 29.6%, P < 0.001; DCR: 85.2% vs. 53.7%, P < 0.001). The median PFS was significantly longer in the TACE-TKI-ICI group (9.9 vs. 5.8 months; P = 0.026). The median OS between the two groups also reached a significant difference (not reached vs. 18.5 months; P = 0.003)., Conclusion: In this retrospective study, the results indicated that the addition of TACE to TKI-ICI therapy could contribute to better tumor control, PFS, and OS benefits in patients with unresectable HCC., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflict of interest., (Copyright © 2024 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.)

Objective: This study aimed to evaluate the clinical safety and efficacy of stent-assisted coil embolization of unruptured wide-necked paraclinoid aneurysms based on the projection distribution., Methods: Between November 2015 and September 2020, 267 unruptured paraclinod aneurysms in 236 patients were identified with a wide neck or unfavorable dome-to-neck ratio and treated with stent-assisted coiling technique. The classification of this segment aneurysms was simplified to the dorsal group (located on the anterior wall) and ventral group (Non-dorsal). Following propensity score matching analysis, the clinical and radiographic data were compared between the two groups., Results: Among 267 aneurysms, 186 were located on the ventral wall and 81 were on the dorsal wall. Dorsal wall aneurysms had a larger size ( p  < .001), wider neck ( p  = .001), and higher dome-to-neck ratio ( p  = .023) compared with ventral wall aneurysms. Propensity score-matched analysis found that dorsal group had a significantly higher likelihood of unfavorable results in immediate (residual sac, 39.4% vs. 18.2%, p  = .007) and follow-up angiography (residual sac, 14.8% vs. 1.9%, p  = .037) compared with ventral group, with significant difference in recurrence rates (9.3% vs. 0%, p  = .028). The rates of procedure-related complications were not significantly different, but one thromboembolic event occurred in the dorsal group with clinical deterioration., Conclusions: Traditional stent-assisted coiling can be given preference in paraclinoid aneurysms located on the ventral wall. The relatively high rate of recurrence in dorsal wall aneurysms with stent assistance may require other treatment options., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Prehospital stroke severity scales have been widely used to identify whether community stroke patients presented with large vessel occlusion (LVO) or not. However, whether these scales are also applicable to in-hospital stroke patients remains unknown., Purpose: We aim to validate and compare the predictive capability of these scales for these patients., Material and Methods: From January 2016 to October 2020, a total of 243 patients who activated in-hospital stroke alerts, were included in this study. The area under the curve (AUC) was used to assess the predictive ability of five scales (Field Assessment Stroke Triage for Emergency Destination [FAST-ED], Rapid Arterial Occlusion Evaluation [RACE], Los Angeles Motor Scale [LAMS], Cincinnati Prehospital Stroke Severity Scale [CPSSS], and Prehospital Acute Stroke Severity scale [PASS]) for LVO. In addition, multivariable logistic analysis was adopted to determine the predictors of LVO in our patients cohort., Results: Finally, 94 (38.7%) patients were confirmed presence of persistent LVO. The AUC for the FAST-ED, RACE, LAMS, CPSSS, and PASS scales to predict the presence of LVO in patients activating in-hospital stroke alerts were 0.82, 0.89, 0.86, 0.81, and 0.79, respectively. After multivariable analysis, baseline NIHSS (adjusted odds ratio [OR] = 1.160, 95% confidence interval [CI] = 1.110-1.212; P < 0.001) atrial fibrillation (adjusted OR = 2.940, 95% CI = 1.387-6.230; P = 0.005) and cardiac/pulmonary procedure (adjusted OR = 6.861, 95% CI = 2.437-19.315; P < 0.001) remained independent predictors of LVO., Conclusion: The prehospital stroke scales also showed good predictive capabilities in discriminating LVO among inpatients who activated stroke alerts. However, given that inpatients' history is more readily available, a specifically designed in-hospital stroke scale that combines stroke severity and history is warranted., (© 2023. The Author(s) under exclusive licence to Belgian Neurological Society.)

Objective: To explore potential predictors of refractory Mycoplasma pneumoniae pneumonia (RMPP) in early stage. Methods: The prospective multicenter study was conducted in Zhejiang, China from May 1 st , 2019 to January 31 st , 2020. A total of 1 428 patients with fever >48 hours to <120 hours were studied. Their clinical data and oral pharyngeal swab samples were collected; Mycoplasma pneumoniae DNA in pharyngeal swab specimens was detected. Patients with positive Mycoplasma pneumoniae DNA results underwent a series of tests, including chest X-ray, complete blood count, C-reactive protein, lactate dehydrogenase (LDH), and procalcitonin. According to the occurrence of RMPP, the patients were divided into two groups, RMPP group and general Mycoplasma pneumoniae pneumonia (GMPP) group. Measurement data between the 2 groups were compared using Mann-Whitney U test. Logistic regression analyses were used to examine the associations between clinical data and RMPP. Receiver operating characteristic (ROC) curves were used to analyse the power of the markers for predicting RMPP. Results: A total of 1 428 patients finished the study, with 801 boys and 627 girls, aged 4.3 (2.7, 6.3) years. Mycoplasma pneumoniae DNA was positive in 534 cases (37.4%), of whom 446 cases (83.5%) were diagnosed with Mycoplasma pneumoniae pneumonia, including 251 boys and 195 girls, aged 5.2 (3.3, 6.9) years. Macrolides-resistant variation was positive in 410 cases (91.9%). Fifty-five cases were with RMPP, 391 cases with GMPP. The peak body temperature before the first visit and LDH levels in RMPP patients were higher than that in GMPP patients (39.6 (39.1, 40.0) vs. 39.2 (38.9, 39.7) ℃, 333 (279, 392) vs. 311 (259, 359) U/L, both P <0.05). Logistic regression showed the prediction probability π=exp (-29.7+0.667×Peak body temperature (℃)+0.004×LDH (U/L))/(1+exp (-29.7+0.667×Peak body temperature (℃)+0.004 × LDH (U/L))), the cut-off value to predict RMPP was 0.12, with a consensus of probability forecast of 0.89, sensitivity of 0.89, and specificity of 0.67; and the area under ROC curve was 0.682 (95% CI 0.593-0.771, P <0.01). Conclusion: In MPP patients with fever over 48 to <120 hours, a prediction probability π of RMPP can be calculated based on the peak body temperature and LDH level before the first visit, which can facilitate early identification of RMPP.

Background: The prevalence of macrolide-resistant Mycoplasma pneumoniae has increased considerably. Treatment in children has become challenging. This study aimed to evaluate the efficacy of doxycycline therapy for macrolide-resistant Mycoplasma pneumoniae pneumonia in children at different periods., Methods: We retrospectively analyzed the data of patients with macrolide-resistant Mycoplasma pneumoniae pneumonia hospitalized between May 2019 to August 2022. According to treatment, patients were divided into three groups: oral doxycycline treatment alone (DOX group), changed from intravenous azithromycin to oral doxycycline (ATD group), and intravenous azithromycin treatment alone (AZI group). ATD group cases were separated into two sub-groups: intravenous azithromycin treatment<3 days (ATD1 group) and ≥ 3 days (ATD2 group). Clinical symptoms were compared in each group and adjusted by Propensity score matching (PSM) analysis., Results: A total of 106 were recruited in this study. 17 (16%) were in DOX group, 58 (55%) in ATD group, and 31(29%) in AZI group. Compared with ATD group and AZI group, the DOX group showed shorter hospitalization duration and fever duration after treatment, while higher rate of chest radiographic improvement. After using PSM analysis, shorter days to hospitalization duration (P = 0.037) and to fever duration after treatment (P = 0.027) in DOX + ATD1 group than in ATD2 group was observed. A higher number of patients in the DOX + ATD1 group achieved defervescence within 72 h (P = 0.031), and fewer children received glucocorticoid adjuvant therapy (P = 0.002). No adverse reactions associated with doxycycline was observed during treatment., Conclusions: Children receiving early oral doxycycline had a shorter duration of fever and hospitalization in macrolide-resistant Mycoplasma pneumoniae patients., (© 2024. The Author(s).)

Objective: This study aimed to provide an alternative approach for quantifying the volume of the ischemic core (IC) if truncation of computed tomography perfusion (CTP) occurs in clinical practice., Methods: Baseline CTP and follow-up diffusion-weighted imaging (DWI) data from 88 patients with stroke were retrospectively collected. CTP source images (CTPSI) from the unenhanced phase to the peak arterial phase (CTPSI-A) or the peak venous phase (CTPSI-V) were collected to simulate the truncation of CTP in the arterial or venous phases, respectively. The volume of IC on CTPSI-A (V CTPSI-A ) or CTPSI-V (V CTPSI-V ) was defined as the volume of the brain tissue with >65% reduction in attenuation compared with that of the normal tissue. The volume of IC on the baseline CTP (V CTP ) was defined as a relative cerebral blood flow of <30% of that in the normal tissue. The volume of the posttreatment infarct on the follow-up DWI (V DWI ) image was manually delineated and calculated. One-way analysis of variance, Bland-Altman plots, and Spearman correlation analyses were used for the statistical analysis., Results: V CTPSI-A was significantly higher than V DWI ( P < 0.001); however, no significant difference was observed between V CTP and V DWI ( P = 0.073) or between V CTPSI-V and V DWI ( P > 0.999). The mean differences between V DWI and V CTPSI-V , V DWI and V CTP , and V DWI and V CTPSI-A were 1.70 mL (limits of agreement [LoA], -56.40 to 59.70), 8.30 mL (LoA, -40.70 to 57.30), and -68.10 mL (LoA, -180.90 to 44.70), respectively. Significant correlations were observed between V DWI and V CTP ( r = 0.68, P < 0.001) and between V DWI and V CTPSI-V ( r = 0.39, P < 0.001); however, no significant correlation was observed between V DWI and V CTPSI-A ( r = 0.20, P = 0.068)., Conclusions: V CTPSI-V may be a promising method for quantifying the volume of the IC if truncation of CTP occurs., Competing Interests: The authors declare no conflict of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: To analyze the use of medicare antiviral drugs (ART) and related factors among HIV-infected people in Ningbo City. Methods: The retrospective data was collected related to infection and treatment of HIV-infected people in ART in Ningbo up to February 2023 through the National Infectious Disease Surveillance System. Binary logistic regression was used to analyze the factors related to medicare antiviral drug use in HIV-infected people. R 4.2.2 software was used for statistical analysis. Results: A total of 6 433 HIV-infected people with ART records were collected, among which 5 783 were in ART. The prevalence of medicare drugs use among people in ART was 24.8% (1 435/5 783, 95% CI : 23.7%-25.9%). Beilun District (8.7%, 43/497) and Fenghua District (5.7%, 14/247) had the lowest level in medicare drugs use. Among people in ART using medicare or out-of-pocket drugs, the prevalence of those who had at least one viral load test in the last year (84.9%, 1 352/1 593) was significantly lower than that of those using free drugs (91.4%, 3 829/4 190) ( χ 2 =52.50, P <0.001). The results of multivariate logistic analysis showed that the factors influencing medicare drug use included low educational level (junior high school and below: a OR =0.24, 95% CI :0.17-0.34), farmer or worker (farmer: a OR =0.60, 95% CI : 0.39-0.91; worker: a OR =0.42, 95% CI : 0.27-0.64), low monthly income (<3 000 Yuan: a OR =0.29, 95% CI : 0.18-0.45), the longer interval time between diagnosis and treatment (≥21 days: a OR =0.47, 95% CI : 0.30-0.74). Conclusions: Significant regional differences on the prevalence of medicare antiviral drugs use in HIV-infected people exist in Ningbo City. Follow-up management program of patients should be improved to strengthen patient compliance to mobilize medicare drug promotion. Meanwhile, publicity of medicare drugs should be strengthened for farmers or workers with low education level and patients with delayed treatment.

Background: The outcome of diffuse angiogram-negative subarachnoid hemorrhage (dan-SAH) compared with aneurysmal SAH (aSAH) remains unclear. This study aimed to compare outcomes using propensity score matching., Methods and Results: Sixty-five patients with dan-SAH and 857 patients with aSAH admitted between January 2018 and December 2022 were retrospectively reviewed. Propensity score matching resulted in matching 65 patients with dan-SAH to 260 patients with aSAH, and clinical outcomes were compared between the groups. Compared with patients with dan-SAH, patients with aSAH were more likely to experience rehemorrhage (8.8% versus 0%, P =0.027), death (11.2% versus 1.5%; odds ratios [OR] 8.04 [95% CI, 1.07-60.12]; P =0.042), or delayed cerebral ischemia (12.3% versus 3.1%; OR, 4.42 [95% CI, 1.03-18.95]; P =0.045). Multivariate analysis revealed that Hunt-Hess grade 4 to 5 (OR, 3.13 [95% CI, 2.11-4.64]; P <0.001), presence of intraventricular hemorrhage (OR, 3.58 [95% CI, 1.72-7.46]; P =0.001), and smoking (OR, 2.44 [95% CI, 1.12-5.28]; P =0.024) were independently associated with the incidence of unfavorable outcomes (modified Rankin scale score >2 at 3 months), whereas dan-SAH was not (OR, 0.66 [95% CI, 0.25-1.73]; P =0.40)., Conclusions: Compared with patients with dan-SAH, patients with aSAH had higher rehemorrhage rates and in-hospital mortality, as well as a higher incidence of delayed cerebral ischemia. Unfavorable outcomes were associated with admission Hunt-Hess grade, the presence of intravenetricular hemorrhage, and smoking history, but there was no relation with the  pathogenesis of the hemorrhage (dan-SAH versus aSAH).

Background: Symptomatic intracranial hemorrhage (sICH) is a common and severe complication in patients with acute ischemic stroke (AIS) after treatment with thrombectomy., Objective: To explore the ability of admission plasma D-dimer levels to predict sICH after thrombectomy., Methods: Between February 2018 and August 2021, consecutive patients with AIS who underwent thrombectomy at our single comprehensive stroke center were retrospectively enrolled. sICH was defined according to the criterion of the Heidelberg Bleeding Classification. Logistic regression analysis was performed to determine the risk factors of sICH. The overall discriminative ability of D-dimer levels in predicting sICH was evaluated by adopting a receiver operating characteristic (ROC) curve., Results: Of the 395 enrolled patients, 48 (12.2%) had sICH. Patients with sICH were older (72.9 vs 69.3 years, P=0.037), more often female (62.5% vs 45.5%, P=0.027), had higher D-dimer levels (2.70 vs 0.74 mg/L, P<0.001), higher National Institutes of Health Stroke Scale score (20 vs 15, P<0.001), lower Alberta Stroke Program Early CT Score (8 vs 9, P<0.001), a higher proportion of internal carotid artery occlusions (56.2% vs 30.3%, P<0.001), and less commonly had large-artery atherosclerosis stroke etiology (12.5% vs 32.3%, P=0.010) than patients without sICH. After adjustment for potential confounders, D-dimer levels (adjusted OR=2.45, 95% CI 1.75 to 3.43, P<0.001) remained significantly associated with sICH. Based on the ROC, the D-dimer as a predictor for predicting sICH, presented with a specificity of 86.2%, a negative predictive value of 94.6%, and an area under the curve of 0.774., Conclusion: Elevated admission D-dimer levels are an independent predictor of sICH in patients with AIS after thrombectomy., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Many challenges remain for long-term survival of renal allografts. Once-daily sirolimus (SRL) combined with low-dose extended-release tacrolimus (LER-TAC) may improve medication adherence and reduce the potential nephrotoxicity of calcineurin inhibitors (CNI) compared with standard immunosuppression regimens, thus potentially improving long-term graft survival., Methods: This retrospective, observational, single-center, propensity score matching (PSM) study compared conversion to SRL combined with low-dose ER-TAC and mycophenolic acid (MPA) combined with standard-dose TAC in kidney transplant recipients. After PSM, there were 56 patients in each group. Efficacy, safety, and medication adherence were evaluated over 12 months., Results: There was no significant difference between the two groups in terms of graft and recipient survival and incidence of biopsy-proven acute rejection ( p  = 1.000), and none of the recipients developed dnDSA after conversion. The mean eGFR improved in SRL + LER-TAC group after conversion compared to before conversion (51.12 ± 20.1 ml/min/1.73 m 2 vs. 56.97 ± 19.23 ml/min/1.73 m 2 , p  < 0.05). The medication adherence at 12 months after conversion was superior to before conversion ( p  = 0.002)., Discussion: Our findings suggest that an immunosuppressive regimen of SRL combined with low-dose ER-TAC is no less effective and safe than standard immunosuppressive regimens for renal transplant recipients and may improve graft renal function and medication adherence., 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 © 2023 Zou, Dai, Hou, Yu, Chen, Chen, Liu, Shi, Gong, Chen, Chen, Chang and Zhang.)

Objective: To compare the prognostic value of net water uptake (NWU) and target mismatch (TM) on CT perfusion (CTP) in acute ischemic stroke (AIS) patients with late time window., Methods: One hundred and nine consecutive AIS patients with anterior-circulation large vessel occlusion presenting within 6-24 h from onset/last seen well were enrolled. Automated Alberta Stroke Program Early CT Score-based NWU (ASPECTS-NWU) was calculated from admission CT. The correlation between ASPECTS-NWU and CTP parameters was assessed. Predictors for favorable outcome (modified Rankin Scale score ≤ 2) at 90 days were assessed using logistic regression analysis. The ability of outcome prediction between ASPECTS-NWU and TM (an ischemic core < 70 mL, a mismatch ratio ≥ 1.8, and an absolute difference ≥ 15 mL) was compared using receiver operating characteristic (ROC) curve., Results: A higher level of ASPECTS-NWU was associated with a larger ischemic core (r = 0.66, p < 0.001) and a larger hypoperfusion volume (r = 0.38, p < 0.001). ASPECTS-NWU performed better than TM for outcome stratification (area under the curve [AUC], 0.738 vs 0.583, p = 0.004) and was the only independent neuroimaging marker associated with favorable outcomes compared with CTP parameters (odds ratio, 0.73; 95% confidence interval [CI] 0.62-0.87, p < 0.001). An outcome prediction model including ASPECTS-NWU and clinical variables (National Institutes of Health Stroke Scale scores and age) yielded an AUC of 0.828 (95% CI 0.744-0.893; sensitivity 65.4%; specificity 87.7%)., Conclusion: ASPECTS-NWU performed better than TM for outcome prediction in AIS patients with late time window and might be an alternative imaging biomarker to CTP for patient selection., Clinical Relevance Statement: Automated Alberta Stroke Program Early CT Score-based net water uptake outperforms target mismatch on CT perfusion for the outcome prediction in patients with acute ischemic stroke and can be an alternative imaging biomarker for patient selection in late therapeutic window., Key Points: • A higher ASPECTS-based net water uptake was associated with larger ischemic cores and hypoperfusion volumes on CT perfusion. • ASPECTS-based net water uptake outperformed target mismatch for outcome prediction in acute ischemic stroke with extended therapeutic window. • ASPECTS-based net water uptake can be an alternative biomarker to target mismatch for selecting acute ischemic stroke patients with late therapeutic window., (© 2023. The Author(s), under exclusive licence to European Society of Radiology.)

Background: Bacterial wilt induced by Ralstonia solanacearum is regarded as one of the most devastating diseases. However, excessive and repeated use of the same bactericides has resulted in development of bacterial resistance. Targeting bacterial virulence factors, such as type III secretion system (T3SS), without inhibiting bacterial growth is a possible assay to discover new antimicrobial agents., Results: In this work, identifying new T3SS inhibitors, a series of mandelic acid derivatives with 2-mercapto-1,3,4-thiazole moiety was synthesized. One of them, F-24, inhibited the transcription of hrpY gene significantly. The presence of this compound obviously attenuated hypersensitive response (HR) without inhibiting bacterial growth of R. solanacearum. The transcription levels of those typical T3SS genes were reduced to various degrees. The test of the ability of F-24 in protecting plants demonstrated that F-24 protected tomato plants against bacterial wilt without restricting the multiplication of R. solanacearum. The mechanism of this T3SS inhibition is through the PhcR-PhcA-PrhG-HrpB pathway., Conculsion: The screened F-24 could inhibit R. solanacearum T3SS and showed better inhibitory activity than previously reported inhibitors without affecting the growth of the strain, and F-24 is a compound with good potential in the control of R. solanacearum. © 2023 Society of Chemical Industry., (© 2023 Society of Chemical Industry.)

Background and Purpose: Recent studies reported the feasibility of quantifying a reliable infarct core (IC) volume using multiphase computed tomography (mCTA) based on deep learning, however its prognostic value was not fully clarified. Therefore, we aimed to evaluate the prognostic value of mCTA-estimated IC volume in patients with acute ischemic stroke (AIS) after mechanical thrombectomy (MT)., Materials and Methods: We retrospectively reviewed patients who underwent mCTA and MT for large vessel occlusion in middle cerebral artery and (or) internal carotid artery within 6 hours after symptom onset between January 2018 and November 2019. Patients were dichotomized into good (modified Rankin Scale [mRS] score, 0-2) and poor (mRS, 3-6) outcome groups. mCTA-estimated IC volume were generated based on a multi-scale three-dimensional convolutional neural network. Univariate, multivariate logistic regression and receiver operating characteristic (ROC) curve analyses were used to identify the independent variables, and evaluate their performances in predicting the clinical outcome., Results: Of 44 included patients, 27 (61.4%) patients achieved good outcome. National Institutes of Health Stroke Scale scores at admission [NIHSSpre] (odds ratio [OR], 1.191; 95%confidence interval [CI], 1.028-1.379; P=0.020) and mCTA-estimated IC volume (OR, 1.076; 95%CI, 1.016-1.140; P=0.013) were found to be independently associated with functional outcome in patients with AIS after MT. After integrating NIHSSpre and mCTA-estimated IC volume, optimal performance (area under the ROC curve, 0.874; 95%CI, 0.739-0.954) could be obtained in predicting the clinical outcome., Conclusions: mCTA-estimated IC volume might be promising for predicting the prognosis, and assisting in making individualized treatment decision in patients with AIS., (Copyright © 2023. Published by Elsevier Ltd.)

Objective: To explore the effect of calcium-independent phospholipase A2 (iPLA2) on the expression of mitochondrial glycerol 3-phosphate dehydrogenase (mGPDH) in human non-alcoholic fatty liver disease cells. Methods: Oleic acid was used to construct a non-alcoholic fatty liver disease cell model by inducing lipid deposition in THLE-2 cells in vitro. Simultaneously, intracellular triglyceride content, iPLA2 expression levels, and mGPDH levels were determined at various induction times (0, 24, 48, and 72 h) using a triglyceride assay kit, quantitative RT-PCR, and western blotting. The model cells were treated with bromelenol lactone, an iPLA2 inhibitor, and N-acetylcysteine, a ROS inhibitor, respectively. Following continuous culture for 24 and 48 hours, the cells were harvested, and the mRNA and protein expression levels of mGPDH were measured. Statistical analysis was performed using the t-test, one-way analysis of variance, and linear correlation. Results: The intracellular triglyceride content gradually increased ( P < 0.01), the mGPDH mRNA and protein expression decreased ( P < 0.01), and the iPLA2 mRNA and protein expression increased ( P < 0.01) in THLE-2 cells with the prolonging time effect of oleic acid therapy. In addition, the mGPDH mRNA expression level was negatively correlated with the iPLA2 mRNA level ( r = -0.878, P = 0.002). The expression levels of mGPDH mRNA and protein in the iPLA2 inhibitor group and ROS inhibitor group were increased compared with the model control group ( P < 0.01). The expression of mGPDH mRNA was increased at 24 h compared with 48 h in the iPLA2 inhibitor group ( P < 0.01). The expression of mGPDH mRNA was gradually increased in the ROS inhibitor group with the prolongation of inhibitor action time ( P < 0.01). Compared with the two inhibitor groups, the increase in mGPDH mRNA was significantly higher in the ROS inhibitor group than that in the iPLA2 inhibitor group, and the difference was statistically significant ( P < 0.01). Conclusion: iPLA2 can inhibit the expression of mGPDH in non-alcoholic fatty liver cells to a certain extent.

Background: Drug resistance is a major obstacle causing chemotherapy failure, and enabling cancer progression. Exosome excreted by cancer cells is participated in cancer progression and chemoresistance, and can be used as an prognostic biomarker. Previous studies have revealed that serum exosomal hsa-circ-0004771 is over-expressed in colorectal cancer (CRC) sufferers and suggested it as a predictive biomarker for early diagnosis and prognosis of CRC. This work will to investigate the role and mechanism of serum exosomal hsa-circ-0004771 in mediating resistance to 5-fluorouracil (5-FU) in CRC., Methods: Serum and tissue samples were collected from 60 patients with CRC/ benign intestinal disease, and 60 healthy control. Exosomes were isolated and identified from serum samples and cell cultured media with TEM, WB, NTA, and flow cytometry. qRT-PCR and WB were performed to evaluate mRNA expressions of exosomal has-circ-0004771 and miR-653, and ZEB2 protein expression, respectively. Cell proliferation, migration, invasion, and apoptosis abilities were assessed with BrdU and colony formation assay, wound-healing assay, and flow cytometry, respectively., Results: Exosomal hsa-circ-0004771 was over-expressed in CRC serum and cell cultured media, while miR-653 was lower-expressed in CRC tissues and cells. Negative correlations existed between exosomal hsa-circ-0004771 in the patients ' serum/cell culture media and miR-653 in CRC tissues/cells, and between miR-653 and ZEB2 in CRC cells. Exosomal hsa-circ-0004771 in CRC cell cultured media was positively related to ZEB2 in CRC cells. MiR-653 was associated with poor prognosis of CRC patients, and its upregulation restrained CRC cell proliferation, migration and invasion, and stimulated apoptosis. Exosomal hsa-circ-0004771 was higher-expressed in 5-FU-resistant CRC serum and cell cultured media, miR-653 was downregulated and ZEB2 was overexpressed in 5-FU-resistant CRC cells. In vitro, exosomal hsa-circ-0004771 in cell cultured media may be involved in 5-FU-resistance by modulating miR-653/ZEB2 pathway., Conclusions: miR-653 plays as a tumour suppressor in CRC progression, and serum exosomal hsa-circ-0004771 may be a predictive biomarker for 5-FU-resistance in CRC patients, potentially through miR-653/ZEB2 axis., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Objective: To evaluate the ability of diffusion-relaxation correlation spectrum imaging (DR-CSI) to predict the consistency and extent of resection (EOR) of pituitary adenomas (PAs)., Methods: Forty-four patients with PAs were prospectively enrolled. Tumor consistency was evaluated at surgery as either soft or hard, followed by histological assessment. In vivo DR-CSI was performed and spectra were segmented following to a peak-based strategy into four compartments, designated A (low ADC), B (mediate ADC, short T2), C (mediate ADC, long T2), and D (high ADC). The corresponding volume fractions ([Formula: see text], [Formula: see text], [Formula: see text], [Formula: see text]) along with the ADC and T2 values were calculated and assessed using univariable analysis for discrimination between hard and soft PAs. Predictors of EOR > 95% were analyzed using logistic regression model and receiver-operating-characteristic analysis., Results: Tumor consistency was classified as soft (n = 28) or hard (n = 16). Hard PAs presented higher [Formula: see text] (p = 0.001) and lower [Formula: see text] (p = 0.013) than soft PAs, while no significant difference was found in other parameters. [Formula: see text] significantly correlated with the level of collagen content (r = 0.448, p = 0.002). Knosp grade (odds ratio [OR], 0.299; 95% confidence interval [CI], 0.124-0.716; p = 0.007) and [Formula: see text] (OR, 0.834, per 1% increase; 95% CI, 0.731-0.951; p = 0.007) were independently associated with EOR > 95%. A prediction model based on these variables yielded an AUC of 0.934 (sensitivity, 90.9%; specificity, 90.9%), outperforming the Knosp grade alone (AUC, 0.785; p < 0.05)., Conclusion: DR-CSI may serve as a promising tool to predict the consistency and EOR of PAs., Clinical Relevance Statement: DR-CSI provides an imaging dimension for characterizing tissue microstructure of PAs and may serve as a promising tool to predict the tumor consistency and extent of resection in patients with PAs., Key Points: • DR-CSI provides an imaging dimension for characterizing tissue microstructure of PAs by visualizing the volume fraction and corresponding spatial distribution of four compartments ([Formula: see text], [Formula: see text], [Formula: see text], [Formula: see text]). • [Formula: see text] correlated with the level of collagen content and may be the best DR-CSI parameter for discrimination between hard and soft PAs. • The combination of Knosp grade and [Formula: see text] achieved an AUC of 0.934 for predicting the total or near-total resection, outperforming the Knosp grade alone (AUC, 0.785)., (© 2023. The Author(s), under exclusive licence to European Society of Radiology.)

Optimizing cell substrates by surface modification of neural stem cells (NSCs), for efficient and oriented neurogenesis, represents a promising strategy for treating neurological diseases. However, developing substrates with the advanced surface functionality, conductivity, and biocompatibility required for practical application is still challenging. Here, Ti 3 C 2 T x MXene is introduced as a coating nanomaterial for aligned poly(l-lactide) (PLLA) nanofibers (M-ANF) to enhance NSC neurogenesis and simultaneously tailor the cell growth direction. Ti 3 C 2 T x MXene treatment provides a superior conductivity substrate with a surface rich in functional groups, hydrophilicity, and roughness, which can provide biochemical and physical cues to support NSC adhesion and proliferation. Moreover, Ti 3 C 2 T x MXene coating significantly promotes NSC differentiation into both neurons and astrocytes. Interestingly, Ti 3 C 2 T x MXene acts synergistically with the alignment of nanofibers to promote the growth of neurites, indicating enhanced maturation of these neurons. RNA sequencing analysis further reveals the molecular mechanism by which Ti 3 C 2 T x MXene modulates the fate of NSCs. Notably, surface modification by Ti 3 C 2 T x MXene mitigates the in vivo foreign body response to implanted PLLA nanofibers. This study confirms that Ti 3 C 2 T x MXene provides multiple advantages for decorating the aligned PLLA nanofibers to cooperatively improve neural regeneration., (© 2023 Wiley-VCH GmbH.)

Roux-en-Y gastric bypass and laparoscopic sleeve gastrectomy characterized by simple operation and few postoperative complications have gradually become the two most commonly used surgical methods in clinical practice.A series of complications often occur after bariatric surgery,including gallstone disease,anemia,malnutrition,gastroesophageal reflux disease,kidney stones,and birth defects in offspring of women of childbearing age.There are controversies regarding the causes and countermeasures of these complications.This article mainly reviews the risk factors and countermeasures for the complications after bariatric surgery.

Purpose: To stratify angiographic images of chronic internal carotid artery occlusion (CICAO) into a newly modified angiographic classification, and identify suitable candidates for endovascular recanalization., Methods: This study included 51 consecutive patients with symptomatic CICAO who underwent endovascular recanalization at our institution. Patients' clinical information, angiographic findings, procedural results, and outcomes were recorded. We attempted to stratify all angiographic images into categories based on morphological occlusive patterns and distal internal carotid artery (ICA) lumen reconstitution on digital subtraction angiography (DSA)., Results: Four types (I-IV) of CICAO were identified based on angiographic characteristics. We defined type I as having a tapered (IA) or blunt stump (IB) and distal ICA lumen reconstitution with collateral filling; type II as having no stump but with distal ICA lumen reconstitution; type III as having a tapered (IIIA) or blunt stump (IIIB) but no distal ICA lumen reconstitution; type IV as having no stump and no distal ICA lumen reconstitution. The rate of successful recanalization was 90.3 % for type I, 60.0 % for type II, 50.0 % for type III, 0 % for type IV, respectively (P = 0.002). The overall intraoperative complication rate was 11.8 %, and none of them led to severe neurological damage or death. The follow-up modified Rankin Scale (mRS) scores were significantly decreased in successfully revascularized patients, whilst there were no significant changes in the other failed patients., Conclusion: For symptomatic CICAO, our newly modified angiographic classification may be comprehensive and useful in selecting suitable patients for recanalization and grading the difficulty of the procedures., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflict of interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Quantitative assessment of endogenously synthesized and released bilirubin from brain tissue remains a challenge. Here, we present a sensitive and reproducible experimental paradigm to quantify, in real time, unconjugated bilirubin (UCB) from isolated murine brain tissue during oxygen-glucose deprivation (OGD). We describe steps for perfusion, brain dissection, brain slice preparation and incubation, glucose depletion, and OGD processing. We then detail procedures for standard calibration plotting and sample UCB measurement. For complete details on the use and execution of this protocol, please refer to Liu et al. 1 ., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background/aims: The current study investigated the incidence, risk factors, and outcomes of acute pancreatitis after percutaneous transhepatic biliary stenting for malignant biliary obstruction., Materials and Methods: From March 2016 to May 2020, a total of 425 patients who underwent percutaneous transhepatic biliary stent- ing for malignant biliary obstruction were included in this 2-center study. After the procedure, we analyzed the incidence, risk factors, and outcomes of acute pancreatitis., Results: On follow-up, 79 (18.6%) patients showed increased serum amylase levels, of whom 41 (9.6%) developed pancreatitis. On binary logistic regression analysis, stent across the duodenal papilla (odds ratio = 8.54; 95% CI = 3.54-20.62; P < .001) and visualization of the pancreatic duct (odds ratio = 9.87; 95% CI = 4.67-20.86; P < .001) were significant risk factors of pancreatitis after the procedure. Using conservative therapy, all patients were successfully managed at a mean of 3.5 days (range 1-6 days), and no severe pancreatitis happened., Conclusion: Acute pancreatitis is a relatively common complication after percutaneous transhepatic biliary stenting. Stent across the duodenal papilla and visualization of the pancreatic duct are independent risk factors.

Background: The Alberta Stroke Program Early CT Score (ASPECTS) and collateral score (CS) are two readily available imaging metrics for the evaluation of acute ischemic stroke (AIS) with large vessel occlusion (LVO)., Objective: To investigate the predictive value of the ASPECTS combined with CS in detecting patients with CT perfusion (CTP) target mismatch in delayed time windows., Methods: One hundred and sixty-four patients with LVO-AIS were included. ASPECTS was assessed on non-contrast CT (NCCT). CS was evaluated on single-phase CT angiography (sCTA). Target mismatch was defined as a CTP core volume ≤70 mL, mismatch ratio ≥1.8, and absolute mismatch volume ≥15 mL. Spearman correlation analysis and receiver operating characteristic curve analyses were performed., Results: The median NCCT ASPECTS of the 164 patients was 8 (IQR 6-9), median sCTA-CS was 2 (IQR 1-2), and median CTP core volume was 8 mL (IQR 0-29.5). There was a strong correlation between NCCT ASPECTS and CTP core volume (r s =-0.756, p<0.0001) and a moderate correlation between the sCTA-CS and CTP core volume (r s =-0.450, p<0.0001). Integrating NCCT ASPECTS and sCTA-CS provided a higher area under the curve (AUC) for predicting target mismatch (AUC=0.882; sensitivity, 89.1%; specificity, 77.8%; p<0.001)., Conclusions: NCCT ASPECTS had a strong correlation with CTP core volumes in patients with LVO-AIS in delayed time windows. Combining NCCT ASPECTS with sCTA-CS resulted in a more accurate prediction of target mismatch. If a CTP scan is not available, NCCT ASPECTS combined with sCTA-CS may guide clinicians in making treatment decisions., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: The effect of pretreatment infarct location on clinical outcome after successful mechanical thrombectomy is not understood. Our aim was to evaluate the association between computed tomography perfusion (CTP)-based ischemic core location and clinical outcome following excellent reperfusion in late time windows., Methods: We retrospectively reviewed patients who underwent thrombectomy for acute anterior circulation large vessel occlusion in late time windows from October 2019 to June 2021 and enrolled 65 patients with visible ischemic core on admission CTP who had received excellent reperfusion (modified thrombolysis in cerebral infarction grade 2c/3). Poor outcome was defined as a modified Rankin scale score of 3-6 at 90 days. The ischemic core infarct territories were classified into the cortical and subcortical areas. Multivariate logistic regression and receiver operating characteristic (ROC) curve analyses were used in this study., Results: Of the 65 patients analyzed, 38 (58.5%) had a poor outcome. Multivariable logistic analysis showed that the subcortical infarcts (OR 11.75; 95% CI 1.79-77.32; P = 0.010) and their volume (OR 1.17; 95% CI 1.04-1.32; P = 0.011) were independently associated with poor outcome. The ROC curve indicated the capacity of the subcortical infarct involvement (areas under the curve (AUC) = 0.65; 95% CI, 0.53-0.77, P < 0.001) and subcortical infarct volume (AUC = 0.72; 95% CI, 0.60-0.83, P < 0.001) in predicting poor outcome accurately., Conclusion: Subcortical infarcts and their volume on admission CTP are associated with poor outcome after excellent reperfusion in late time windows, rather than cortical infarcts., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)