While current treatments for multiple sclerosis (MS) targeting T or B cells have shown clinical benefit, they remain insufficient due to the multifactorial and dynamic nature of MS pathogenesis. A key obstacle to restoring immune homeostasis lies in the reciprocal reinforcement between endothelial-to-mesenchymal transition (EndMT) and sustained immune infiltration, which collectively exacerbate blood-brain barrier (BBB) disruption and neuroinflammation. We identified IL7R as a shared target on endothelial cells and pathogenic T cells via scRNA-seq and developed a multifunctional nanodelivery platform-ETS1 pDNA/PBAE@ITP-MM (IMNP)-comprising ETS1 plasmid DNA complexed with poly(β-amino ester) (PBAE), an interleukin-7 receptor (IL7R)-targeting peptide (ITP), and a macrophage membrane (MM) coating. IMNP concurrently modulates endothelial cells and T lymphocytes for synergistic efficacy. Exploiting the intrinsic inflammation-targeting capacity of activated macrophage membranes and ITP conjugation, IMNPs preferentially accumulate at the vascular endothelium, where they inhibit EndMT and preserve BBB integrity. Subsequently, IMNPs attenuate differentiation of CD4+ T cells into proinflammatory Th1/Th17 subsets, thereby reducing CNS infiltration and re-establishing immune microenvironmental balance in both relapsing-remitting MS (RRMS) and secondary progressive MS (SPMS) models. Our findings provide proof-of-concept for a biomimetic nanoplatform that achieves dual vascular-immune modulation, significantly alleviating neuroinflammation, reducing demyelination, and improving motor performance in both RRMS and SPMS models.
To develop and validate a CT radiomics model for predicting microsatellite instability (MSI) status in preoperative gastric cancer (GC) patients and to explore the underlying immune infiltration pattern of the radiomics model. This study used three retrospective datasets from Tongji Hospital (n = 304, training set), Xiangyang Central Hospital (n = 48, external testing set 1) and public datasets from The Cancer Imaging Archive (TCIA) (n = 43, external testing set 2). The preoperative contrast-enhanced CT images of GC were evaluated. Radiomics features were extracted and selected to construct the radiomics model in the training set, and further validated in the other two external testing sets. The outcome cohort, including 68 advanced unresectable GC patients receiving immunotherapy, was used to assess the predictive value of the radiomics model for treatment response and outcomes. We analyzed RNA-sequencing data from TCIA to investigate the underlying genomics characterization and immune infiltration spectrum of the radiomics model. Four radiomic features were ultimately selected to develop the radiomics model. The model demonstrated good predictive performance for MSI status, achieving AUCs of 0.952, 0.835, and 0.879 in the training set and the two external testing sets, respectively. Radiomics scores (Radscores) was an independent predictor for PFS in the outcome cohort (HR: 0.145; 95
Despite substantial evidence highlighting molecular communication within the components of neurovascular units (NVU), the interactions at the organelle level have been insufficiently explored in recent decades. Mitochondria, for instance, beyond their traditional role as energy supply for intracellular metabolism and survival, provide a novel perspective on intercellular connections through mitochondrial transfer. These transferred mitochondria not only carry bioactive molecules but also signal to mitigate risks in both healthy and pathological conditions. In this review, we summarized mitochondrial transfer events, relevant routes, and underlying molecular mechanisms originating from diverse cell populations within NVU. We particularly focus on the therapeutic potential of this mechanism in treating central nervous system disorders, notably neurodegenerative diseases marked by mitochondrial dysfunction and then highlight the promising prospects of exogenous mitochondrial supplementation as a treatment target.
PurposeTo assess the utility of fat fraction quantification using quantitative multi-echo Dixon for evaluating tumor proliferation and microvascular invasion (MVI) in hepatocellular carcinoma (HCC).MethodsA total of 66 patients with resection and histopathologic confirmed HCC were enrolled. Preoperative MRI with proton density fat fraction and R2* mapping was analyzed. Intratumoral and peritumoral regions were delineated with manually placed regions of interest at the maximum level of intratumoral fat. Correlation analysis explored the relationship between fat fraction and Ki67. The fat fraction and R2* were compared between high Ki67(>30%) and low Ki67 nodules, and between MVI negative and positive groups. Receiver operating characteristic (ROC) analysis was used for further analysis if statistically different.ResultsThe median fat fraction of tumor (tFF) was higher than peritumor liver (5.24% vs 3.51%, P=0.012). The tFF was negatively correlated with Ki67 (r=-0.306, P=0.012), and tFF of high Ki67 nodules was lower than that of low Ki67 nodules (2.10% vs 4.90%, P=0.001). The tFF was a good estimator for low proliferation nodules (AUC 0.747, cut-off 3.39%, sensitivity 0.778, specificity 0.692). There was no significant difference in tFF and R2* between MVI positive and negative nodules (3.00% vs 2.90%, P=0.784; 55.80s-1 vs 49.15s-1, P=0.227).ConclusionWe infer that intratumor fat can be identified in HCC and fat fraction quantification using quantitative multi-echo Dixon can distinguish low proliferative HCCs.
Introduction Sarcopenia is associated with adverse outcomes in patients with malignancies, it remains unclear whether the sex discrepancy of sarcopenia or muscle loss leads to different prognoses in patients with mass-forming intrahepatic cholangiocarcinoma (MICC). Material and methods Patients who were pathologically diagnosed with MICC and underwent partial hepatectomy between 2012 and 2019 were recruited. Fat-free muscle areas (FFMA) were defined as areas of bilateral erector spinae muscles on dual-echo T1-weighted gradient-recalled-echo images at the level of radix of the superior mesenteric artery. FFMI (fat-free skeletal muscle index) was calculated by dividing FFMA by individual’s height squared. The prognostic value of FFMI was investigated using Kaplan-Meier method and multivariable Cox regressions in both the entire cohort and sex-specific subgroups. Results A total of 157 patients were finally included. Cutoff values for the definition of low FFMI were 14.19 cm2/m2 in males and 11.07 cm2/m2 in females. Patients with low FFMI had significantly shorter overall survival (OS) than those with high FFMI in the entire cohort (19.42 vs 35.29 months, p=0.0067) and male patients (17.25 vs 37.19 months, p=0.006), but not females. Multivariate analyses showed that low FFMI was a significant predictor of OS in the entire cohort (HR 1.725, 95%CI 1.054-2.821, p=0.03) and male patients (HR 2.145, 95%CI 1.113-4.133, p=0.023). No association between FFMI and disease-free survival was found in both the entire cohort and sex-specific subgroups. Conclusions Preoperative FFMI measured by MRI is a prognostic biomarker for OS in MICC patients, and it is more sensitive in males than in females.
ObjectivesTo develop and validate a contrast-enhanced CT-based radiomics nomogram for the diagnosis of neuroendocrine carcinoma of the digestive system. MethodsThe clinical data and contrast-enhanced CT images of 60 patients with pathologically confirmed neuroendocrine carcinoma of the digestive system and 60 patients with non-neuroendocrine carcinoma of the digestive system were retrospectively collected from August 2015 to December 2021 at Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, and randomly divided into a training cohort (n=84) and a validation cohort (n=36). Clinical characteristics were analyzed by logistic regression and a clinical diagnosis model was developed. Radiomics signature were established by extracting radiomic features from contrast-enhanced CT images. Based on the radiomic signature and clinical characteristics, radiomic nomogram was developed. ROC curves and Delong's test were used to evaluate the diagnostic efficacy of the three models, calibration curves and application decision curves were used to analyze the accuracy and clinical application value of nomogram. ResultsLogistic regression results showed that TNM stage (stage IV) (OR 6.8, 95% CI 1.320-43.164, p=0. 028) was an independent factor affecting the diagnosis for NECs of the digestive system, and a clinical model was constructed based on TNM stage (stage IV). The AUCs of the clinical model, radiomics signature, and radiomics nomogram for the diagnosis of NECs of the digestive system in the training, validation cohorts and pooled patients were 0.643, 0.893, 0.913; 0.722, 0.867, 0.932 and 0.667, 0.887, 0.917 respectively. The AUCs of radiomics signature and radiomics nomogram were higher than clinical model, with statistically significant difference (Z=4.46, 6.85, both p < 0.001); the AUC difference between radiomics signature and radiomics nomogram was not statistically significant (Z=1.63, p = 0.104). The results of the calibration curve showed favorable agreement between the predicted values of the nomogram and the pathological results, and the decision curve analysis indicated that the nomogram had favorable application in clinical practice. ConclusionsThe nomogram constructed based on contrast-enhanced CT radiomics and clinical characteristics was able to effectively diagnose neuroendocrine carcinoma of the digestive system.
Abstract Purpose The purpose of this study was to test the hypothesis that brain white matter hyperintensities (WMH) are more common in patients receiving epidermal growth factor receptor tyrosine kinase inhibitor (EGFR‐TKI) and identify clinical risk factors associated with WMH. Experimental design This multiple‐center, prospective cohort study was conducted from March 2017 to July 2020. Two groups of patients with non‐small cell lung cancer (NSCLC) who received or did not receive EGFR‐TKI were included and followed up for more than 24 months. The progression of WMH was defined as an increase of ≥1 point on the Fazekas visual rating scale between the baseline and at the 2‐year follow‐up. A modified Poisson regression model was performed to evaluate risk factors on increased WMH load. Results Among 286 patients with NSCLC, 194 (68%) patients with NSCLC who received EGFR‐TKI and 92 (32%) patients with NSCLC without EGFR‐TKI treatment were analyzed. Modified Poisson regression analysis showed that EGFR‐TKI treatment was independently associated with the WMH progression (EGFR‐TKI: aRR 2.72, 95% confidence interval [CI] 1.46–5.06, p = .002). Interleukin (IL)‐2, IL‐4, and IL‐10 were associated with increased WMH in the adjusted model (IL‐2: aRR 1.55 [95% CI 1.06–2.25], p = .023; IL‐4: aRR 1.66 [95% CI 1.13–2.43], p = .010; IL‐10: aRR 1.48 [95% CI 1.06–2.06], p = .020). Conclusion Patients with NSCLC who received EGFR‐TKI may be at higher risk of developing WMH or worsening of WMH burden. The impact of increased WMH lesions in these patients is to be further assessed. IL‐2, IL‐4, and IL‐10 may be used as potential biomarkers to monitor the risk of increased WMH burden
The purpose of this study was to test the hypothesis that brain white matter hyperintensities (WMH) are more common in patients receiving epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) and identify clinical risk factors associated with WMH. This multiple-center, prospective cohort study was conducted from March 2017 to July 2020. Two groups of patients with non-small cell lung cancer (NSCLC) who received or did not receive EGFR-TKI were included and followed up for more than 24 months. The progression of WMH was defined as an increase of ≥1 point on the Fazekas visual rating scale between the baseline and at the 2-year follow-up. A modified Poisson regression model was performed to evaluate risk factors on increased WMH load. Among 286 patients with NSCLC, 194 (68%) patients with NSCLC who received EGFR-TKI and 92 (32%) patients with NSCLC without EGFR-TKI treatment were analyzed. Modified Poisson regression analysis showed that EGFR-TKI treatment was independently associated with the WMH progression (EGFR-TKI: aRR 2.72, 95% confidence interval [CI] 1.46–5.06, p = .002). Interleukin (IL)-2, IL-4, and IL-10 were associated with increased WMH in the adjusted model (IL-2: aRR 1.55 [95% CI 1.06–2.25], p = .023; IL-4: aRR 1.66 [95% CI 1.13–2.43], p = .010; IL-10: aRR 1.48 [95% CI 1.06–2.06], p = .020). Patients with NSCLC who received EGFR-TKI may be at higher risk of developing WMH or worsening of WMH burden. The impact of increased WMH lesions in these patients is to be further assessed. IL-2, IL-4, and IL-10 may be used as potential biomarkers to monitor the risk of increased WMH burden
Background Thrombocytopenia is a common adverse event of oxaliplatin-based chemotherapy. Grade 2 or higher oxaliplatin-related thrombocytopenia may result in dose reduction, discontinuation or delay initiation of chemotherapy and may adversely affect the therapeutic efficacy and even overall survival of patients. Early recognition of patients at risk of developing grade 2 or higher thrombocytopenia is critical. However, to date there is no well-established method to early identify patients at high risk. The aims of this study were to develop and validate a contrast-enhanced CT-based whole-spleen radiomics signature for early prediction of grade 2 or higher thrombocytopenia in patients with gastrointestinal malignancies treated with oxaliplatin-based chemotherapy and to explore the incremental value of combining the radiomics signature and conventional clinical factors for risk prediction. Methods A total of 119 patients with gastrointestinal malignancies receiving oxaliplatin-based chemotherapy from March 2017 to December 2020 were retrospectively included and randomly divided into a training cohort (n = 85) and a validation cohort (n = 34). Grade 2 or higher thrombocytopenia occurred in 26.1% of patients (22 and nine patients in the training and validation cohort, respectively) with a median time interval of 101 days from the start of chemotherapy. The whole-spleen radiomics features were extracted on the portal venous phase of the first follow-up CT images. The least absolute shrinkage and selection operator (LASSO) algorithm was applied to select radiomics features and to build the radiomics signature for the prediction of grade 2 or higher thrombocytopenia. A clinical model that included clinical factors only and a clinical-radiomics model that incorporated clinical factors and radiomics signature were constructed. The performances of both models were evaluated and compared in the training, validation and the whole cohorts. Results The radiomics signature yielded favorable performance in predicting grade 2 or higher thrombocytopenia, with the area under the curve (AUC), sensitivity and specificity being 0.865, 81.8% and 84.1% in the training cohort and 0.747, 77.8% and 80.0% in the validation cohort. The AUCs of the clinical-radiomics model in the training and validation cohorts reached 0.913 (95% CI [0.720–0.935]) and 0.867 (95% CI [0.727–1.000]), greater than the AUCs of the clinical model. Integrated discrimination improvement (IDI) index showed that incorporating radiomic signature into conventional clinical factors significantly improved the predictive accuracy by 17.0% (95% CI [4.9%–29.1%], p = 0.006) in the whole cohort. Conclusions Contrast-enhanced CT-based whole-spleen radiomics signature might serve as an early predictor for grade 2 or higher thrombocytopenia during oxaliplatin-based chemotherapy in patients with gastrointestinal malignancies and provide incremental value over conventional clinical factors.
The aim of this study was to elucidate the application of ultrasound examination of umbilical artery (UA) hemodynamics with urine microalbumin (UmA) determination in evaluating the outcomes of sPE patients. Altogether 80 sPE patients and 75 healthy pregnant women were recruited. UmA, RI (resistance index) and PI (pulsatility index) were separately measured by ELISA and the ultrasonic Doppler flow detector. The correlation between parameters was analysed using Pearson's coefficient method. The independent risk factors of sPE were identified using the Logistic regression model. sPE patients had increased UmA, RI and PI (all p < 0.05). UmA level was positively correlated with RI and PI in sPE patients. RI, PI and UmA were independent risk factors of sPE (all p < 0.05). sPE can predict adverse pregnancy outcomes. High UmA levels may increase the risk of poor prognosis. Overall, ultrasound examination of UA hemodynamics with UmA determination can predict the adverse pregnancy outcomes of sPE patients. IMPACT STATEMENT What is already known on this subject? Doppler ultrasound and urine microalbumin (UmA) measurement are important tools in assessing the clinical severity of severe preeclampsia (sPE). What do the results of this study add? This study aims to unravel the application of ultrasound examination of hemodynamics in the umbilical artery (UA) combined with the determination of UmA in evaluating the outcomes of sPE patients. What are the implications of these findings for clinical practice and/or further research? Ultrasound examination of hemodynamics in UA combined with the determination of UmA can predict the adverse pregnancy outcomes of sPE patients.
Radioresistance of prostate cancer (PCa) is a major factor leading to local failure of radiotherapy. STAT3 is an oncogenic protein that was recently found to be activated in PCa tumors. This study aimed to investigate the radiosensitization effect of targeting STAT3 in PCa tumors. Here, the radiosensitization effect of STAT3 blockade was investigated by clonogenic assay, flow cytometry and western blot analysis in human PCa cells in vitro and in vivo. We demonstrated that STAT3 blockade with a STAT3 inhibitor or siRNA increased the radiosensitivity of PCa cells and that radiation together with STAT3 blockade induced more apoptosis and double-strand breaks (DSBs) than radiation alone in LNCaP cells. In addition, radiation induced STAT3 activation and survivin expression in PCa cells, which was inhibited by STAT3 blockade. Transfection with survivin cDNA attenuated the radiosensitization effect of STAT3 blockade. These effects were further confirmed by in vivo studies, which showed that the STAT3 inhibitor enhanced the treatment efficacy of radiation on LNCaP xenografts with decreased STAT3 activation and survivin expression. These findings suggest that STAT3 blockade radiosensitizes PCa cells through regulation of survivin. Thus, our study has revealed STAT3 as a potential sensitizer for irradiation in PCa cells. Its clinical application as an adjuvant in radiotherapy of PCa should be explored in the future.
目的:探讨血管内皮抑制素联合经动脉导管化疗栓塞术(T ACE)治疗HCC的疗效,及其对肿瘤组织CT纹理特征的影响.方法:搜集89例HCC患者的临床和CT资料.其中37例(观察组)接受血管内皮抑制素联合T ACE治疗,52例(对照组)接受常规T ACE治疗.于治疗前4周内和治疗后4~8周内分别行三期动态增强CT检查.按mRECIST标准评价两组疗效.使用FireVoxel软件在两组患者治疗前、后门静脉期薄层CT图像上人工勾画病灶的全容积感兴趣区(VOI)后进行纹理分析,提取16个灰度直方图参数值.比较两组间疗效和治疗前、后灰度直方图参数值的差异.对于差异有统计学意义的纹理参数,采用ROC曲线分析其诊断效能,计算曲线下面积(A U C).结果:疗效为完全缓解(CR)、部分缓解(PR)和稳定(SD)和进展者,在观察组中分别为6、12和8例,在对照组中分别为4、10和14例,两组疗效的差异有统计学意义(Z=-2.045,P<0.05).治疗后有6个灰度直方图参数值在两组之间的差异有统计学意义(P<0.05),包括标准差、不均一性、峰度、熵、及第90和95百分位数.ROC曲线分析结果显示熵、第95百分位数和标准差的诊断效能较高,AUC分别为0.701、0.677和0.670.结论:与单纯T ACE治疗相比,血管内皮抑制素联合T ACE治疗HCC可明显提高疗效,且肿瘤组织的纹理特征有一定差异.
Angiogenesis, an essential restorative process following ischemia, is a promising therapeutic approach to improve neurological deficits. However, overcoming the blood–brain barrier (BBB) and effective drug enrichment are challenges for conventional drug delivery methods, which has limited the development of treatment strategies. Herein, a dual‐targeted therapeutic strategy is reported to enable pH‐sensitive drug release and allow cerebral ischemia targeting to improve stroke therapeutic efficacy. Targeted delivery is achieved by surface conjugation of Pro‐His‐Ser‐Arg‐Asn (PHSRN) peptides, which binds to integrin α 5 β 1 enriched in the cerebral vasculature of ischemic tissue. Subsequently, smoothened agonist (SAG), an activator of sonic hedgehog (Shh) signaling, is coupled to PHSRN‐HES by pH‐dependent electrostatic adsorption. SAG@PHSRN‐HES nanoparticles can sensitively release more SAG in the acidic environment of ischemic brain tissue. More importantly, SAG@PHSRN‐HES exerts the synergistic mechanisms of PHSRN and SAG to promote angiogenesis and BBB integrity, thus improving neuroplasticity and neurological function recovery. This study proposes a new approach to improve the delivery of medications in the ischemic brain. Dual‐targeted therapeutic strategies have excellent potential to treat patients suffering from cerebral infarction.
探讨基于多模态影像的3D打印教学模具在泌尿系统医学影像学教学中的应用.构建泌尿系统疾病3D打印教学模具.对实验组进行课前及课后问卷调查.比较实验组和对照组泌尿系统医学影像学考试成绩.结果显示基于多模态影像的3D打印教学模具能够激发学生学习泌尿系统医学影像学的兴趣并有助于知识的理解记忆,提高考试成绩.
BACKGROUND AND PURPOSE:Satellite sign is a novel neuroimaging marker for predicting hematoma expansion (HE), which is closely related to unfavorable prognosis in patients with spontaneous intracerebral hemorrhage (ICH). However, the predictive value of satellite sign varied according to previous studies. Thus, we conduct this meta-analysis to systematically review the application value of satellite sign in related studies.METHODS:We searched the literature in PubMed, Embase, and Web of Science from inception to April 10, 2020. Effect values, including sensitivity, specificity, and positive and negative likelihood ratio were pooled to assess the diagnostic value of satellite sign for HE in patients with ICH.RESULTS:The meta-analysis included five studies with a total of 1493 patients. Results showed that the pooled diagnostic sensitivity and specificity were 0.50 (95 % CI, 0.31-0.70) and 0.71 (95 % CI, 0.56-0.83), respectively. In addition, the pooled positive and negative likelihood ratios were 1.7 (95 % CI, 1.5-2.1) and 0.70 (95 % CI, 0.54-0.89), respectively. No significant publication bias was found.CONCLUSION:Satellite sign exhibited moderate sensitivity and specificity for predicting HE in patients with ICH. Further studies are needed to explore its value in clinical application.
文章探讨了影像专业直播教学的必要性和可行性,探讨了如何利用高清视频会议系统在附属医院放射科与课堂之间建立直播教学的技术和应用方法,以及在直播教学中注意事项.直播教学就是运用现代视频技术和网络通信技术,通过现场直播的方式将教学内容实时传输给远端学生进行教学的交互式教学方式.直播教学通过视频会议系统,与医院PACS系统相连,实现相应影像图像的播放,阅片医师及学生可以实时对图像进行诊断.直播教学能够为学生提供丰富多样的影像诊断病例,以及提供理论与实践相结合的机会,在提高学习兴趣,发现问题,弥补缺失方面有积极的作用;除此之外,直播教学有利于病例影像资料收集,对提高老师教学能力、业务素质也有积极促进的作用.
2018年RSNA年会上腹部影像学方面的研究热点主要包括人工智能、影像组学/纹理分析和能谱CT的基础研究和临床应用,为今后的临床和科研工作开拓了新的思路.
目的:回顾性分析小肾嗜酸细胞腺瘤及小肾透明细胞癌的影像表现,总结病灶的增强CT表现及鉴别要点.方法:记录并分析10例小肾嗜酸细胞腺瘤及20例小肾透明细胞癌病灶的部位、边缘、密度、有无钙化、囊变、坏死、与正常肾实质夹角、中心星状瘢痕、节段强化反转征及假包膜测量并分析腹部三期增强CT中病灶与正常肾皮质的CT值.结果:两组间病灶与正常肾实质夹角(P=0.008)、中心星状瘢痕(P=0.030)及节段强化反转征(P=0.002)有统计学差异.将病灶与正常肾实质夹角(角度)、中心星状瘢痕(瘢痕)、节段强化反转征(反转)进行组合,分别进行模型1(角度+瘢痕+反转)、模型2(角度+瘢痕)、模型3(角度+反转)、模型4(瘢痕+反转)预测分析,其中模型1和3的敏感度较高(100%),而模型4特异度较高(100%),AUC值从高到低依次为模型1(0.930)、3(0.912)、2(0.830)、4(0.800).两组间病灶的CT值及与皮质的比值无明显统计学差异(P>0.05).结论:对于无症状偶然发现的小肾皮质肿块,突出于肾轮廓外、与肾实质夹角为钝角,伴中心瘢痕及节段强化反转,可提示倾向于肾嗜酸细胞腺瘤的诊断.
2012年的RSNA胸部研究热点主要集中在COPD肺功能的影像学评估、肺肿瘤的诊断和鉴别诊断、胸部低剂量CT扫描技术及肺栓塞的影像诊断,重点是肺特殊气体应用、PET-CT与MRI-PT的对比研究及肺能谱CT的应用等.