Radiation-induced pulmonary fibrosis (RIPF) is a chronic fibrotic lung disease triggered by ionizing radiation exposure and is characterized by abnormal epithelial-mesenchymal transition (EMT), fibroblast proliferation and activation, and excessive extracellular matrix (ECM) deposition. As a late-stage pulmonary complication of radiation exposure, RIPF lacks effective clinical interventions. Although nintedanib and pirfenidone are approved antifibrotic drugs for idiopathic pulmonary fibrosis (IPF), their efficacy against RIPF remains insufficiently validated. The precise pathogenesis of RIPF remains incompletely understood; however, accumulating evidence highlights the critical regulatory role of epigenetic modifications, particularly microRNAs (miRNAs), in the development and progression of RIPF. Here, we summarize the regulatory mechanisms of miRNAs in RIPF, and highlight their clinical potential and current research challenges, aiming to advance miRNA-related research in RIPF.

RATIONALE AND OBJECTIVES:The clinical feature and long-term prognosis of unilateral moyamoya disease (MMD) have not been fully described and studied. The study aimed to investigate independent risk factors for stroke in unilateral MMD patients during a long-term follow-up. MATERIALS AND METHODS:A total of 393 unilateral MMD patients (median age, 40 years) were assessed at baseline and followed for an average time of 68.9 months. Ischemic and hemorrhagic stroke incidence rates were determined. Multiple demographic, clinical and neuroimaging factors at baseline were considered as potential predictors of stroke during the follow-up period. Hazard ratios (HR) and corresponding 95% confidence interval (CI) for stroke were calculated by univariable and multivariable Cox proportional hazards models. Cumulative risk of stroke was estimated by the Kaplan-Meier product-limit method. RESULTS:During the follow-up period, 43 patients experienced stroke events (10.9%). 5 children experienced stroke events (5/46, 10.9%) and 38 adults experienced stroke events (38/347, 11.0%) (P>0.05). 21 patients with encephaloduroarteriosynangiosis (EDAS) experienced stroke events (21/254, 8.3%) and 22 patients with conservative treatment experienced stroke events (22/139, 15.8%) (P<0.05). After adjustment for clinical characteristics, multivariable analysis showed that involvement of posterior cerebral artery (HR, 2.199; 95% CI, 1.100-4.398), decreased cerebral blood flow (CBF) (HR, 2.292; 95% CI, 1.182-4.446) and concentric enhancement of the arterial wall (HR, 3.093; 95% CI, 1.617-5.915) were significantly associated with stroke, and EDAS (HR, 0.385; 95% CI, 0.203-0.730) and compensatory blood supply by anterior communicating artery (HR, 0.413; 95% CI, 0.206-0.830) were protective factors for stroke. CONCLUSION:Involvement of posterior cerebral artery, decreased CBF, concentric enhancement of the arterial wall, EDAS and compensatory blood supply by anterior communicating artery may help stratify the risk of stroke and improve therapeutic decisions in unilateral MMD. Unilateral MMD could benefit from EDAS and have a lower risk of future stroke.

To evaluate the role of vessel wall enhancement in the efficacy of antiplatelet therapy (APT) on reducing the stroke risk in patients with Moyamoya disease (MMD) based on postcontrast MR vessel wall imaging. Consecutive patients with MMD underwent postcontrast MR vessel wall imaging and were divided into APT and non-APT groups according to the prescribed antiplatelet agents. Kaplan−Meier survival and Cox regression analyses were performed to determine the association between APT and stroke risk of patients with MMD, and subgroup analysis was performed to determine the role of vessel wall enhancement in reducing stroke risk after APT. A total of 1262 patients (mean age: 42.6 ± 11.1 years) were finally included for analysis. Compared with patients without APT, those with APT were older (p = 0.023) and had a higher incidence of hypertension (p = 0.015), and with advanced Suzuki stage (≥ IV) (p < 0.001). During an average follow-up of 37.9 months, patients without APT had a marginally greater incidence of cerebrovascular events (12.9

BACKGROUND: Moyamoya disease (MMD) is a cerebrovascular disorder characterized by the progressive stenosis of the intracranial internal carotid artery and the development of a collateral network in the brain. As medical imaging technology and artificial intelligence have advanced, various imaging methods have been widely used in the clinical diagnosis of MMD. In this study, we conducted bibliometric visualization of research papers about MMD and radiological features between 2000 and 2024, intending to explore the development status quo, hotspots, and future developments and contributing to studies on imaging in diagnosis of cerebrovascular diseases. METHODS: The Web of Science Core Collection was chosen as the source of publications for this study. By using VOSviewer and CiteSpace, articles were analyzed in terms of authors, countries, institutions, references, keywords, cited literatures, and so on. RESULTS: We retrieved a collection of 1003 articles that substantiate a progressively ascendant trend in articles over the past 24 years. Japan, South Korea, and China were 3 major countries in this field. China's Capital Medical University was the leader in publication output, followed by Hokkaido University from Japan and Seoul National University from South Korea. The 3 authors with the most publications were Miki Fujimura, Teiji Tominaga, and Dong Zhang. World Neurosurgery was the journal with the most publications (85), while Stroke was the journal with the most cocitations (3305) in this field. Excluding MMD, the top 3 most frequently occurring keywords were "revascularization", "stroke", and "magnetic resonance imaging (MRI)". "High-resolution magnetic resonance imaging (HRMRI)", "digital subtraction angiography (DSA)", and "vessel wall imaging" were the top 3 keywords of recent interest in the field of radiological features. CONCLUSIONS: This article provides a scientific perspective from which researchers, especially doctors in neurosurgery and radiodiagnosis departments can visually find out about important trends and new areas of research directions in the field of MMD and radiological features.

Autophagy is an evolutionarily conserved process of cell self-catabolism that provides a minimum level of energy for cellular homeostasis during metabolic stress. In radiotherapy (RT), it has been explicitly explained that autophagy plays a dual role in tumour control by tuning cellular radiosensitivity. However, the underlying molecular mechanism remains a conundrum. Therefore, it is of utmost importance to gain insight into the molecular mechanisms elaborating the autophagy-mediated radiosensitivity and craft refined RT strategies for different tumours. Distinguishing it from previous reviews in the field, here we discuss the mechanisms of autophagy, especially its pro-survival and growth-suppressing mechanisms via regulation of radiosensitivity. We further outline some frontier RT adjuvant therapies targeting autophagy, in an endeavour to shed some light on the autophagy-mediated pathways to harness radiosensitivity.

To evaluate the predictive performance of a clinical-CT-radiomics nomogram based on radiomics signature and independent clinical-CT predictors for predicting endoscopic red color sign (RC) in cirrhotic patients with esophageal varices (EV). We retrospectively evaluated 215 cirrhotic patients. Among them, 108 and 107 cases were positive and negative for endoscopic RC, respectively. Patients were assigned to a training cohort (n = 150) and a validation cohort (n = 65) at a 7:3 ratio. In the training cohort, univariate and multivariate logistic regression analyses were performed on clinical and CT features to develop a clinical-CT model. Radiomic features were extracted from portal venous phase CT images to generate a Radiomic score (Rad-score) and to construct five machine learning models. A combined model was built using clinical-CT predictors and Rad-score through logistic regression. The performance of different models was evaluated using the receiver operating characteristic (ROC) curves and the area under the curve (AUC). The spleen-to-platelet ratio, liver volume, splenic vein diameter, and superior mesenteric vein diameter were independent predictors. Six radiomics features were selected to construct five machine learning models. The adaptive boosting model showed excellent predictive performance, achieving an AUC of 0.964 in the validation cohort, while the combined model achieved the highest predictive accuracy with an AUC of 0.985 in the validation cohort. The clinical-CT-radiomics nomogram demonstrates high predictive accuracy for endoscopic RC in cirrhotic patients with EV, which provides a novel tool for non-invasive prediction of esophageal varices bleeding.

Ionizing radiation (IR) induced damages are common complications of radiotherapy for tumors, severely limiting the intensity and therapeutic efficacy of the radiotherapy program. Emerging data indicated that the cGAS-STING pathway has paradoxical effects on IR-induced damage. SR-717, as a non-nucleotide, small-molecule stimulator of interferon genes (STING) agonist, has been proven that it could activate the STING signaling pathway. In this work, we try to explore the radioprotection of the STING signaling pathway and figure out whether SR-717 could be a potential intestinal radioprotective agent. C57BL/6 mice were intraperitoneally treated with SR-717 or normal saline (NS). By analyzing the survival rate, body weight, and the number of peripheral blood cells after IR exposure, we found that SR-717 improved the survival rate and body weight of mice, protected the intestine from IR-induced damage as well as hematopoietic damage, and promoted the regeneration of intestinal stem cells (ISCs). Cell viability and apoptosis after irradiation were detected after stimulation of MODE-K cells with SR-717 or PBS. We found that SR-717 increased cell viability and inhibited apoptosis in vitro. The mechanism of SR-717 in intestinal radiation protection was investigated by RNA-seq. The results of RNA-seq and qRT-PCR suggested that SR-717 significantly activated the immune system via the STING-IL-6 signaling pathway. In addition, we discussed the role of TLR2 in SR-717-mediated anti-radiation activity, and TLR2 deletion significantly reversed the radioprotective effects of SR717. In conclusion, we proved STING signaling activation displayed anti-radiation activity and found SR-717 displayed anti-radiation activity via the STING-IL-6 signaling pathway, suggesting SR-717 could be a potential intestinal radioprotective agent.

The long-term effects and outcomes of human mesenchymal stem cell (MSC) therapy in patients with severe coronavirus disease 2019 (COVID-19) remain poorly understood. This study aimed to evaluate the extended safety and efficacy of MSC treatment in severe patients with COVID-19 who participated in our earlier randomized, double-blind, placebo-controlled clinical trial, with follow-up conducted over 3 years. One hundred patients with severe COVID-19 were randomized to receive either an MSC infusion (n = 65, 4 × 107 cells/dose, on days 0, 3, and 6) or a placebo, with both groups receiving the standard of care. At 36 months post-MSC therapy, patients were followed up to long-term safety and efficacy, particularly the effects of MSC therapy on persistent COVID-19 symptoms. Evaluated outcomes included lung imaging results, 6-min walking distance (6-MWD), pulmonary function test results, quality of life scores based on the Short Form-36 (SF-36) health survey, Long COVID symptoms, new-onset comorbidities, tumor marker levels, and rates of COVID-19 reinfection. Three years post-treatment, 46.94 https://clinicaltrials.gov/study/NCT04288102 .

Chronic kidney disease (CKD) poses a major global public health challenge. The World Health Organization's data shows that CKD affects about 10% of the world's population, particularly in low- and middle-income countries. Due to limited access to diagnosis and treatment, CKD has become the 12th leading cause of death worldwide. The advanced stage of CKD can lead to kidney failure, which is clinically referred to as end-stage renal disease (ESRD). In such cases, patients can only sustain life through dialysis or kidney transplantation. However, the long-term affordability of these treatments remains low. Moreover, the effectiveness of kidney transplantation is modest, posing a significant treatment barrier in resource-limited settings, and significantly impacting patient survival. To address this issue, we suggest using dietary supplementation of the trace element zinc to impede CKD development and prolong patient survival.

Ionising radiation exposure can lead to acute haematopoietic radiation syndrome. Despite significant advancements in the field of radioprotection, no drugs with high efficacy and low toxicity have yet been approved by the Food and Drug Administration. FG-4592, as a proline hydroxylase inhibitor, may play an important role in radioprotection of the haematopoietic system. Mice were peritoneal injected with FG-4592 or normal saline. After irradiation, the survival time, body weight, peripheral blood cell and bone marrow cell (BMC) count, cell apoptosis, pathology were analysed and RNA-sequence technique (RNA-Seq) was conducted to explore the mechanism of FG-4592 in the haematopoietic system. Our results indicated that FG-4592 improved the survival rate and weight of irradiated mice and protected the spleen, thymus and bone marrow from IR-induced injury. The number of BMCs was increased and protected against IR-induced apoptosis. FG-4592 also promoted the recovery of the blood system and erythroid differentiation. The results of RNA-Seq and Western blot showed that the NF-κB signalling pathway and hypoxia-inducible factor-1 (HIF-1) signalling pathway were upregulated by FG-4592. Meanwhile, RT-PCR results showed that FG-4592 could promote inflammatory response significantly. FG-4592 exhibited radioprotective effects in the haematopoietic system by promoting inflammatory response and targeting the NF-κB, HIF signalling pathway.

There is strong evidence connecting increased serum lipid levels to cardiovascular disorders, including atherosclerosis. Statins is prescribed as the primary medication to decrease lipid levels. Recent research has demonstrated that hydrogen possesses anti-inflammatory and antioxidant properties by modulating the expression of peroxisome proliferator-activated receptor gamma coactivator-1α, ultimately leading to the preservation of lipid homeostasis. Magnesium hydride (MgH 2 ) is a prolonged stable hydrogen storage medium, which can be utilized to investigate its synergistic lipid-lowering effect with statins and its detailed molecular mechanism, both in vivo and in vitro . To ascertain the safety and efficacy of MgH 2 , we executed a comprehensive research of its influence on both physiological and pathological metrics. We noted a substantial diminution in lipid levels when MgH 2 was integrated with atorvastatin, as attested by oil red staining. Furthermore, we scrutinized the regulatory effect of MgH 2 on cytochrome P450 3A, which is a metabolic enzyme of statins, and discovered that it could be reduced by the MgH 2 . Concluding from our results, we propose that MgH 2 inhibits the expression of cytochrome P450 3A in the liver and exerts an auxiliary lipid-lowering effect by increasing the blood concentration of statins. By augmenting our comprehension of MgH 2 's role in ameliorating lipid metabolism, we aspire to develop more promising therapies in the future.

Purpose: This study aimed to evaluate the ability of MRI-based intratumoral and peritumoral radiomics features of liver tumors to differentiate between hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC) and to predict ICC differentiation. Methods: This study retrospectively collected 87 HCC patients and 75 ICC patients who were confirmed pathologically. The standard region of interest (ROI) of the lesion drawn by the radiologist manually shrank inward and expanded outward to form multiple ROI extended regions. A three-step feature selection method was used to select important radiomics features and convolution features from extended regions. The predictive performance of several machine learning classifiers on dominant feature sets was compared. The extended region performance was assessed by area under the curve (AUC), specificity, sensitivity, F1 -score and accuracy. Results: The performance of the model is further improved by incorporating convolution features. Compared with the standard ROI, the extended region obtained better prediction performance, among which 6 mm extended region had the best prediction ability (Classification: AUC = 0.96, F1 -score = 0.94, Accuracy: 0.94; Grading: AUC = 0.94, F1 -score = 0.93, Accuracy = 0.89). Conclusion: Larger extended region and fusion features can improve tumor predictive performance and have potential value in tumor radiology.

Purposes Radiotherapy can induce tumor cell autophagy, which might impair the antitumoral effect. This study aims to investigate the effect of autophagy inhibition on the targeted radionuclide therapy (TRT) efficacy of 131 I-FAP-2286 in pancreatic cancer. Methods Human pancreatic cancer PANC-1 cells were exposed to 131 I-FAP-2286 radiotherapy alone or with the autophagy inhibitor 3-MA. The autophagy level and proliferative activity of PANC-1 cells were analyzed. The pancreatic cancer xenograft-bearing nude mice were established by the co-injection of PANC-1 cells and pancreatic cancer-associated fibroblasts (CAFs), and then were randomly divided into four groups and treated with saline (control group), 3-MA, 131 I-FAP-2286 and 131 I-FAP-2286 + 3-MA, respectively. SPECT/CT imaging was performed to evaluate the bio-distribution of 131 I-FAP-2286 in pancreatic cancer-bearing mice. The therapeutic effect of tumor was evaluated by 18 F-FDG PET/CT imaging, tumor volume measurements, and the hematoxylin and eosin (H&E) staining, and immunohistochemical staining assay of tumor tissues. Results 131 I-FAP-2286 inhibited proliferation and increased the autophagy level of PANC-1 cells in a dose-dependent manner. 3-MA promoted 131 I-FAP-2286-induced apoptosis of PANC-1 cells via suppressing autophagy. SPECT/CT imaging of pancreatic cancer xenograft-bearing nude mice showed that 131 I-FAP-2286 can target the tumor effectively. According to 18 F-FDG PET/CT imaging, the tumor growth curves and immunohistochemical analysis, 131 I-FAP-2286 TRT was capable of suppressing the growth of pancreatic tumor accompanying with autophagy induction, but the addition of 3-MA enabled 131 I-FAP-2286 to achieve a better therapeutic effect along with the autophagy inhibition. In addition, 3-MA alone did not inhibit tumor growth. Conclusions 131 I-FAP-2286 exposure induces the protective autophagy of pancreatic cancer cells, and the application of autophagy inhibitor is capable of enhancing the TRT therapeutic effect.

Background: Intestinal tissue is extremely sensitive to ionizing radiation (IR), which is easy to cause intestinal radiation sickness, and the mortality rate is very high after exposure. Recent studies have found that intestinal immune cells and intestinal stem cells (ISCs) may play a key role in IR-induced intestinal injury. Methods: C57BL6 mice matched for age, sex and weight were randomly grouped and intraperitoneal injected with PBS, Scleroglucan (125.0 mg/kg) or Anti-mouse IL-17A -InVivo (10 mg/kg), the number of mice in each group was n >= 3.Survival time, body weight, pathology, organoids and immune cell markers of the mice after IR (10.0 Gy) were compared, and the mechanism of action in intestinal tissues was verified by transcriptome sequencing. Results: Scleroglucan has significant radiation protective effects on the intestine, including improving the survival rate of irradiated mice, inhibiting the radiation damage of intestinal tissue, and promoting the proliferation and differentiation of intestinal stem cells (ISCs). The results of RNA sequencing suggested that Scleroglucan could significantly activate the immune system and up-regulate the IL-17 and NF-kappa B signaling pathways. Flow cytometry showed that Scleroglucan could significantly up-regulate the number of Th17 cells and the level of IL17A in the gut. IL-17A provides radiation protection. After intraperitoneal injection of Scleroglucan and Antimouse IL-17A -InVivo, mice can significantly reverse the radiation protection effect of Scleroglucan, downregulate the molecular markers of intestinal stem cells and the associated markers of DC, Th1 and Th17 cells, and up-regulate the associated markers of Treg and Macrophage cells. Conclusion: Scleroglucan may promote the proliferation and regeneration of ISCs by regulating the activation of intestinal immune function mediated by IL-17 signaling pathway and play a protective role in IR-induced injury.

BACKGROUND:Little is known about the association between stroke and imaging and clinical features in conservatively treated patients with moyamoya disease (MMD). PURPOSE:To investigate independent risk factors for stroke in conservatively treated patients with MMD during a long-term follow-up. STUDY TYPE:Prospective study. SUBJECTS:One hundred sixty conservatively managed patients with MMD (median age 46 years, 89 male). FIELD STRENGTH/SEQUENCE:Time of flight, turbo inversion recovery magnitude T1WI, turbo spin echo (TSE) T2WI, echo-planar imaging DWI, T2-fluid attenuated inversion recovery, dynamic susceptibility contrast-magnetic resonance imaging, and pre- and post-contrast 3D TSE T1WI sequences at 3.0 Tesla. ASSESSMENT:Patients were assessed at baseline and followed yearly. Ischemic and hemorrhagic stroke incidence rates were determined. Multiple demographic, clinical (modified Rankin score [mRS]), and cerebral imaging (cerebral blood volume [CBV] and concentric enhancement of arterial wall) factors at baseline were considered as potential predictors of stroke during the follow-up period. STATISTICAL TESTS:Univariable and multivariable Cox proportional hazards models to calculate the hazard ratios (HRs) and corresponding 95% confidence interval (CI) for stroke. Cumulative risk of stroke was estimated by the Kaplan-Meier product-limit method. A P value <0.05 was considered statistically significant. RESULTS:The median follow-up duration was 47 months. During the follow-up period, 18 (11.25%) patients experienced stroke events (13 [8.13%] ischemic, 5 [3.12%] hemorrhagic). Univariable analysis showed that 11 factors were significantly associated with stroke. After adjustment for clinical characteristics, multivariable analysis showed that mRS score ≥3 (HR, 1.99; 95% CI, 1.26-3.14), decreased CBV (HR, 5.31; 95% CI, 2.32-12.13), and concentric enhancement of the arterial wall (HR, 4.16; 95% CI, 1.55-11.15) were significantly associated with stroke. DATA CONCLUSION:Decreased CBV, mRS score ≥ 3, and concentric enhancement of the arterial wall were significantly associated with increased incidence of stroke in conservatively treated MMD. EVIDENCE LEVEL:2 TECHNICAL EFFICACY: Stage 4.

Background This study explores the potential of the deep learning-based convolutional neural network (CNN) to automatically recognize MMD using MRA images from atherosclerotic disease (ASD) and normal control (NC). Methods In this retrospective study in China, 600 participants (200 MMD, 200 ASD and 200 NC) were collected from one institution as an internal dataset for training and 60 from another institution were collected as external testing set for validation. All participants were divided into training (N = 450) and validation sets (N = 90), internal testing set (N = 60), and external testing set (N = 60). The input to the CNN models comprised preprocessed MRA images, while the output was a tripartite classification label that identified the patient's diagnostic group. The performances of 3D CNN models were evaluated using a comprehensive set of metrics such as area under the curve (AUC) and accuracy. Gradient-weighted Class Activation Mapping (Grad-CAM) was used to visualize the CNN's decision-making process in MMD diagnosis by highlighting key areas. Finally, the diagnostic performances of the CNN models were compared with those of two experienced radiologists. Findings DenseNet-121 exhibited superior discrimination capabilities, achieving a macro-average AUC of 0.977 (95% CI, 0.928-0.995) in the internal test sets and 0.880 (95% CI, 0.786-0.937) in the external validation sets, thus exhibiting comparable diagnostic capabilities to those of human radiologists. In the binary classification where ASD and NC were group together, with MMD as the separate group for targeted detection, DenseNet-121 achieved an accuracy of 0.967 (95% CI, 0.886-0.991). Additionally, the Grad-CAM results for the MMD, with areas of intense redness indicating critical areas identified by the model, reflected decision-making similar to human experts. Interpretation This study highlights the efficacy of CNN model in the automated diagnosis of MMD on MRA images, easing the workload on radiologists and promising integration into clinical workflows.

Intracranial vessel wall enhancement (VWE) on high-resolution magnetic resonance imaging (HRMRI) is associated with the progression and poor prognosis of moyamoya disease (MMD). This study assessed potential risk factors for VWE in MMD. We evaluated MMD patients using HRMRI and traditional angiography examinations. The participants were divided into VWE and non-VWE groups based on HRMRI. Logistic regression was performed to compare the risk factors for VWE in MMD. The incidence of cerebrovascular events of the different subgroups according to risk factors was compared using Kaplan–Meier survival and Cox regression. We included 283 MMD patients, 84 of whom had VWE on HRMRI. The VWE group had higher modified Rankin Scale scores at admission (p = 0.014) and a higher incidence of ischaemia and haemorrhage (p = 0.002) than did the non-VWE group. Risk factors for VWE included the ring finger protein 213 (RNF213) p.R4810K variant (odds ratio [OR] 2.01, 95