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Objectives: Thrombomodulin (TM) is closely related to the pathogenesis of autoimmune diseases, including systemic lupus erythematosus (SLE). However, current evidence on circulating TM levels in SLE patients is contradictory. We conducted this meta-analysis to more accurately assess circulating TM levels in patients with SLE and lupus nephritis (LN) and to analyze related influencing factors. Methods: Systematic search of relevant documents was conducted in PubMed, Embase, and The Cochrane Library databases (up to 28 February 2021). Studies on the comparison of circulating TM between SLE patients and controls were screened and evaluated for inclusion. Random-effects model analysis was applied to calculate the combined standardized mean difference (SMD) with a 95% confidence interval (CI). Heterogeneity was estimated by Q statistics and I2. Results: A total of 353 articles were identified, 14 provided adequate information for this study finally. The results illustrated that SLE patients had higher TM levels than healthy controls (SMD=0.38, 95% CI: 0.02 to 0.74, p=0.04). Circulating TM levels were increased in patients with active SLE compared to inactive SLE patients (SMD=1.12, 95% CI: 0.03 to 2.20, p=0.04). In addition, circulating TM levels of SLE patients with LN were higher than those without LN (SMD=4.55, 95% CI: 1.97 to 7.12, p=0.001). Conclusions: The circulating TM levels in SLE patients are enhanced. In addition, circulating TM levels may be practical in reflecting the disease activity and nephritis involvement of SLE patients.

Clinical evaluations of long-term outcomes in the early-stage spinal cord injury (SCI) focus on macroscopic motor performance and are limited in their prognostic precision. This study was designed to investigate the sensitivity of the magnetic resonance imaging (MRI) indexes to the data-driven gait process after SCI. Ten adult female rhesus monkeys were subjected to thoracic SCI. Kinematics-based gait examinations were performed at 1 (early stage) and 12 (chronic stage) months post-SCI. The proportion of stepping (PS) and gait stability (GS) were calculated as the outcome measures. MRI metrics, which were derived from structural imaging (spinal cord cross-sectional area, SCA) and diffusion tensor imaging (fractional anisotropy, FA; axial diffusivity, λ//), were acquired in the early stage and compared with functional outcomes by using correlation analysis and stepwise multivariable linear regression. Residual tissue SCA at the injury epicenter and residual tissue FA/remote normal-like tissue FA were correlated with the early-stage PS and GS. The extent of lesion site λ///residual tissue λ// in the early stage after SCI was correlated with the chronic-stage GS. The ratios of lesion site λ// to residual tissue λ// and early-stage GS were predictive of the improvement in the PS at follow-up. Similarly, the ratios of lesion site λ// to residual tissue λ// and early-stage PS best predicted chronic GS recovery. Our findings demonstrate the predictive power of MRI combined with the early data-driven gait indexes for long-term outcomes. Such an approach may help clinicians to predict functional recovery accurately.

Advanced Non-alcoholic fatty liver disease (NAFLD) is associated with increased risk of cardiovascular disease (CVD).We determine whether combinations of ultrasound graphic steatosis grades, fibrosis scores and apolipoprotein levels add value to CVD risk prediction in NAFLD patients.The retrospective cohort study enrolled 10,453 individuals (3519 NAFLD; 6934 non NAFLD) from 2004 to 2018. Hepatic ultrasound measurements, lipid and apolipoprotein profiles, Fibrosis-4 and the NAFLD fibrosis scores (NFS) were assessed. The primary outcome included both clinical and subclinical CVD.During 116-month follow-up period, there were 957 clinical and 752 subclinical CVD events. NAFLD patients had a higher incidence of CVD than non NAFLD patients as the steatosis degree, NFS, and FIB4 scores increased (25.1% vs 11.9%, Log Rank: p 0.001). For the lipid and apolipoprotein profiles excluding triglyceride or ApoE, subjects with varied steatosis severity in the upper two tertiles had different risk of CVD (p for interaction 0.001). A nomogram model combination of Framingham Risk Score (FRS), NFS and apolipoprotein profiles presented a higher AUC than FRS in a time-dependent ROC curve (0.816 vs 0.752, p 0.001).The novel risk score considering ultrasonography-defined steatosis grades, non-invasive liver fibrosis scores and apolipoprotein profiles accurately predicted the 10-year risk of CVD.

Zhi Dong,1,* Yingyu Lin,1,* Fangzeng Lin,2,* Xuyi Luo,3 Zhi Lin,1 Yinhong Zhang,1 Lujie Li,1 Zi-Ping Li,1 Shi-Ting Feng,1 Huasong Cai,1 Zhenpeng Peng1 1Department of Radiology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, 510080, People’s Republic of China; 2Department of Interventional Radiology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, 510080, People’s Republic of China; 3Department of Emergency, Guangzhou First People’s Hospital, Guangzhou, Guangdong, 510180, People’s Republic of China*These authors contributed equally to this workCorrespondence: Huasong Cai; Zhenpeng PengDepartment of Radiology, The First Affiliated Hospital, Sun Yat-Sen University, 58th, The Second Zhongshan Road, Guangzhou, Guangdong, People’s Republic of ChinaTel +86 20-87755766, extension 8471Fax +86 20-87615805Email caihuas@mail.sysu.edu.cn; pengzhp@mail.sysu.edu.cnPurpose: The treatment response to initial conventional transarterial chemoembolization (cTACE) is essential for the prognosis of patients with hepatocellular carcinoma (HCC). This study explored and verified the feasibility of machine-learning models based on clinical data and contrast-enhanced computed tomography (CT) image findings to predict early responses of HCC patients after initial cTACE treatment.Patients and Methods: Overall, 110 consecutive unresectable HCC patients who were treated with cTACE for the first time were retrospectively enrolled. Clinical data and imaging features based on contrast-enhanced CT were collected for the selection of characteristics. Treatment responses were evaluated based on the modified Response Evaluation Criteria in Solid Tumors (mRECIST) by postoperative CT examination within 2 months after the procedure. Python (version 3.70) was used to develop machine learning models. Least absolute shrinkage and selection operator (LASSO) algorithm was applied to select features with the impact on predicting treatment response after the first TACE procedure. Six machine learning algorithms were used to build predictive models, including XGBoost, decision tree, support vector machine, random forest, k-nearest neighbor, and fully convolutional networks, and their performances were compared using receiver operator characteristic (ROC) curves to determine the best performing model.Results: Following TACE, 31 patients (28.2%) were described as responsive to TACE, while 72 patients (71.8%) were nonresponsive to TACE. Portal vein tumor thrombosis type, albumin level, and distribution of tumors within the liver were selected for predictive model building. Among the models, the RF model showed the best performance, with area under the curve (AUC), accuracy, sensitivity, and specificity of 0.802, 0.784, 0.904, and 0.480, respectively.Conclusion: Machine learning models can provide an accurate prediction of the early response of initial TACE treatment for HCC, which can help in individualizing clinical decision-making and modification of further treatment strategies for patients with unresectable HCC.Keywords: hepatocellular carcinoma, transarterial chemoembolization, machine learning, prediction model, treatment response

Objectives To develop and validate a radiomics model for evaluating treatment response to immune-checkpoint inhibitor plus chemotherapy (ICI + CT) in patients with advanced esophageal squamous cell carcinoma (ESCC). Methods A total of 64 patients with advance ESCC receiving first-line ICI + CT at two centers between January 2019 and June 2020 were enrolled in this study. Both 2D ROIs and 3D ROIs were segmented. ComBat correction was applied to minimize the potential bias on the results due to different scan protocols. A total of 788 features were extracted and radiomics models were built on corrected/uncorrected 2D and 3D features by using 5-fold cross-validation. The performance of the radiomics models was assessed by its discrimination, calibration and clinical usefulness with independent validation. Results Five features and support vector machine algorithm were selected to build the 2D uncorrected, 2D corrected, 3D uncorrected and 3D corrected radiomics models. The 2D radiomics models significantly outperformed the 3D radiomics models in both primary and validation cohorts. When ComBat correction was used, the performance of 2D models was better (p = 0.0059) in the training cohort, and significantly better (p Conclusions The easy-to-use 2D corrected radiomics model could facilitate noninvasive preselection of ESCC patients who would benefit from ICI + CT.

BACKGROUND: Among patients with stable coronary disease and moderate or severe ischemia, whether clinical outcomes are better in those who receive an invasive intervention plus medical therapy than in those who receive medical therapy alone is uncertain. METHODS: We randomly assigned 5179 patients with moderate or severe ischemia to an initial invasive strategy (angiography and revascularization when feasible) and medical therapy or to an initial conservative strategy of medical therapy alone and angiography if medical therapy failed. The primary outcome was a composite of death from cardiovascular causes, myocardial infarction, or hospitalization for unstable angina, heart failure, or resuscitated cardiac arrest. A key secondary outcome was death from cardiovascular causes or myocardial infarction. RESULTS: Over a median of 3.2 years, 318 primary outcome events occurred in the invasive-strategy group and 352 occurred in the conservative-strategy group. At 6 months, the cumulative event rate was 5.3% in the invasive-strategy group and 3.4% in the conservative-strategy group (difference, 1.9 percentage points; 95% confidence interval [CI], 0.8 to 3.0); at 5 years, the cumulative event rate was 16.4% and 18.2%, respectively (difference, -1.8 percentage points; 95% CI, -4.7 to 1.0). Results were similar with respect to the key secondary outcome. The incidence of the primary outcome was sensitive to the definition of myocardial infarction; a secondary analysis yielded more procedural myocardial infarctions of uncertain clinical importance. There were 145 deaths in the invasive-strategy group and 144 deaths in the conservative-strategy group (hazard ratio, 1.05; 95% CI, 0.83 to 1.32). CONCLUSIONS: Among patients with stable coronary disease and moderate or severe ischemia, we did not find evidence that an initial invasive strategy, as compared with an initial conservative strategy, reduced the risk of ischemic cardiovascular events or death from any cause over a median of 3.2 years. The trial findings were sensitive to the definition of myocardial infarction that was used. (Funded by the National Heart, Lung, and Blood Institute and others; ISCHEMIA ClinicalTrials.gov number, NCT01471522.).

Cowden syndrome (CS) is a rare, autosomal dominant, multisystem disease related to the mutation of phosphatase and tensin homolog (PTEN) tumor suppressor gene. It is characterized by the occurrence of multiple hamartomas and mucocutaneous lesions and is associated with a high risk of malignancies. Lhermitte-Duclos disease (LDD), or dysplastic cerebellar gangliocytoma, is a rare hamartomatous lesion of the cerebellar cortex with a unique “tiger stripe” appearance on magnetic resonance imaging (MRI). Since 1991, LDD has been considered pathognomonic and part of CS. In addition, as almost all adult onset LDD cases were associated with PTEN gene mutations, LDD and CS are both included in PTEN hamartoma tumor syndrome (PHTS). In this article, we report a 48-year-old female patient, who presented with a right cerebellar lesion resulting in hydrocephalus. The histology of the cerebellar lesion confirmed the diagnosis of LDD, and her clinical history is highly suggestive of CS. Due to the high incidence of multisystemic malignancies and other diseases, it is important for clinicians to be aware of the association between LDD and CS. Affected patients should be evaluated carefully and screened for cancers accordingly, so as to allow early diagnosis and treatment.

Objective To identify predictor microRNAs (miRNAs) from patients with repeated implantation failure (RIF). Design Systemic analysis of miRNA profiles from the endometrium of patients undergoing in vitro fertilization (IVF). Setting University research institute, private IVF center, and molecular testing laboratory. Patient(s) Twenty five infertile patients in the discovery cohort and 11 patients in the validation cohort. Interventions(s) None. Main Outcome Measure(s) A signature set of miRNA associated with the risk of RIF. Result(s) We designed a reproductive disease-related PanelChip to access endometrium miRNA profiles in patients undergoing IVF. Three major miRNA signatures, including hsa-miR-20b-5p, hsa-miR-155-5p, and hsa-miR-718, were identified using infinite combination signature search algorithm analysis from 25 patients in the discovery cohort undergoing IVF. These miRNAs were used as biomarkers in the validation cohort of 11 patients. Finally, the 3-miRNA signature was capable of predicting patients with RIF with an accuracy >90%. Conclusion(s) Our findings indicated that specific endometrial miRNAs can be applied as diagnostic biomarkers to predict RIF. Such information will definitely help to increase the success rate of implantation practice.

Yuying Chen,1,&ast; Jia Chen,2,&ast; Yu Zhang,3,&ast; Zhi Lin,1 Meng Wang,1 Lifei Huang,2 Mengqi Huang,1 Mimi Tang,1 Xiaoqi Zhou,1 Zhenpeng Peng,1 Bingsheng Huang,2 Shi-Ting Feng1 1Department of Radiology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, People’s Republic of China; 2Medical AI Lab, School of Biomedical Engineering, Health Science Center, Shenzhen University, Shenzhen, Guangdong, People’s Republic of China; 3Department of Pathology, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Bingsheng HuangMedical AI Lab, School of Biomedical Engineering, Health Science Center, Shenzhen University, Shenzhen, Guangdong, People’s Republic of ChinaTel +86 755-86172208Fax +86 755-86171820Email huangb@szu.edu.cnShi-Ting FengDepartment of Radiology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, People’s Republic of ChinaTel +86 20-87755766 Ext 8471Fax +86 20-87615805Email fengsht@mail.sysu.edu.cnPurpose: Cytokeratin 19 (CK19) expression is a proven independent prognostic predictor of hepatocellular carcinoma (HCC). This study aimed to develop and validate the performance of a deep learning radiomics (DLR) model for CK19 identification in HCC based on preoperative gadoxetic acid-enhanced magnetic resonance imaging (MRI).Patients and Methods: A total of 141 surgically confirmed HCCs with preoperative gadoxetic acid-enhanced MRI from two institutions were included. Prediction models were established based on hepatobiliary phase (HBP) images using a training set (n=102) and validated using time-independent (n=19) and external (n=20) test sets. A receiver operating characteristic curve was used to evaluate the performance for CK19 prediction. Recurrence-free survival (RFS) was also analyzed by incorporating the CK19 expression and other factors.Results: For predicting CK19 expression, the area under the curve (AUC) of the DLR model was 0.820 (95% confidence interval [CI]: 0.732– 0.907, P< 0.001) with sensitivity, specificity, accuracy of 0.800, 0.766, and 0.775, respectively, and reached 0.781 in the external test set. Combined with alpha fetoprotein, the AUC increased to 0.833 (95% CI: 0.753– 0.912, P

Background Excessive delivery of free fatty acids (FFAs) to the liver promotes steatosis and insulin resistance (IR), with IR defined as reduced glucose uptake, glycogen synthesis and anti-lipolysis stimulated by normal insulin levels. Whether the associations between FFAs and diabetes development differ between patients with and without nonalcoholic fatty liver disease (NAFLD) remains unclear. Methods Consecutive subjects (2,220 NAFLD subjects and 1,790 non-NAFLD subjects according to ultrasound imaging) were enrolled from the First Affiliated Hospital of Sun Yat-sen University between 2009 and 2019. The homeostasis model assessment of insulin resistance (HOMA-IR) was calculated. Results There was an approximate J-shaped relationship between FFA levels and HOMA-IR in the NAFLD group. Higher FFA concentration quartiles were associated with higher risks of IR (odds ratio [OR], 9.24; 95% confidence interval [CI], 6.43 to 13.36), prediabetes (OR, 10.48; 95% CI, 5.66 to 19.39), and type 2 diabetes mellitus (T2DM; OR, 19.43; 95% CI, 12.75 to 29.81) in the NAFLD group but not in the non-NAFLD group. The cut-off points for the FFA levels increased in a stepwise manner in discriminating IR, prediabetes and T2DM (573, 697, and 715 μmol/L) in the NAFLD group but not in non-NAFLD individuals. Conclusion A distinct dose-dependent relationship of FFA levels was found with IR, prediabetes and T2DM in NAFLD patients. Screening serum FFA levels in NAFLD patients would be valuable in preventing diabetes development.

Mitochondrial reactive oxygen species (mtROS)-induced apoptosis has been suggested to contribute to myocardial ischemia/reperfusion injury. Interleukin 35 (IL-35), a novel anti-inflammatory cytokine, has been shown to protect the myocardium and inhibit mtROS production. However, its effect on cardiomyocytes upon exposure to hypoxia/reoxygenation (H/R) damage has not yet been elucidated. The present study aimed to investigate the potential protective role and underlying mechanisms of IL-35 in H/R-induced mouse neonatal cardiomyocyte injury. Mouse neonatal cardiomyocytes were challenged to H/R in the presence of IL-35, and we found that IL-35 dose dependently promotes cell viability, diminishes mtROS, maintains mitochondrial membrane potential, and decreases the number of apoptotic cardiomyocytes. Meanwhile, IL-35 remarkably activates mitochondrial STAT3 (mitoSTAT3) signaling, inhibits cytochrome c release, and reduces apoptosis signaling. Furthermore, co-treatment of the cardiomyocytes with the STAT3 inhibitor AG490 abrogates the IL-35-induced cardioprotective effects. Our study identified the protective role of IL-35 in cardiomyocytes following H/R damage and revealed that IL-35 protects cardiomyocytes against mtROS-induced apoptosis through the mitoSTAT3 signaling pathway during H/R.

Background and Aims Emerging evidence points to a link between creeping fat and the pathogenesis of Crohn’s disease [CD]. Non-invasive assessment of the severity of creeping fat on cross-sectional imaging modality has seldom been investigated. This study aimed to develop and characterize a novel mesenteric creeping fat index [MCFI] based on computed tomography [CT] in CD patients. Methods MCFI was developed based on vascular findings on CT in a retrospective cohort [n = 91] and validated in a prospective cohort [n = 30]. The severity of creeping fat was graded based on the extent to which mesenteric fat extended around the intestinal circumference using the vessels in the fat as a marker. The accuracy of MCFI was assessed by comparing it with the degree of creeping fat observed in surgical specimens. The relationship between MCFI and fibrostenosis was characterized by determining if these correlated. The accuracy of MCFI was compared with other radiographic indices [i.e. visceral to subcutaneous fat area ratio and fibrofatty proliferation score]. Results In the retrospective cohort, MCFI had moderate accuracy in differentiating moderate–severe from mild fibrostenosis (area under the receiver operating characteristic [ROC] curve [AUC] = 0.799; p = 0.000). ROC analysis in the retrospective cohort identified a threshold MCFI of > 3 which accurately differentiated fibrostenosis severity in the prospective cohort [AUC = 0.756; p = 0.018]. An excellent correlation was shown between MCFI and the extent of fat wrapping in specimens in the prospective cohort [r = 0.840, p = 0.000]. Neither visceral to subcutaneous fat area ratio nor fibrofatty proliferation score correlated well with the degree of intestinal fibrosis. Conclusions MCFI can accurately characterize the extent of mesenteric fat wrapping in surgical specimens. It may become another non-invasive measure of CD fibrostenosis.

Background The purpose of this study was to investigate the feasibility of CT parameters to predict the presence of KRAS mutations in rectal cancer patients. The relationship between the presence of a KRAS mutation and pathological findings was evaluated simultaneously. Methods Eighty-nine patients (29 females, 60 males, age 27-90, mean 59.7±12 years) with pathologically proven rectal cancer were enrolled. A KRAS mutation test was completed following surgery. Parameters evaluated on CT included the tumor location, the diameter of the superior rectal vein (SRV) and inferior mesenteric vein (IMV), the presence of calcification, ulceration, lymph node enlargement (LNE), distant metastasis, tumor shape (intraluminal polypoid mass, infiltrative mass, or bulky), circumferential extent (C0-C1/4, C1/4-C1/2, C1/2-C3/4, or C3/4-C1), enhanced pattern (homogeneous or heterogeneous), CT ratio, and the length of the tumor (LOT). Pathological findings included lymphovascular emboli, signet ring cell, peripheral fat interval infiltration, focal ulcer, lymph node metastasis, tumor pathological type, and differentiation extent. The correlations between KRAS status and CT parameters, and KRAS status and pathological findings were investigated. The accuracy of CT characteristics for predicting KRAS mutation was evaluated. Results A KRAS mutation was detected in 42 cases. On CT image, the diameter of the SRV was significantly increased in the KRAS mutation group compared to in the KRAS wild-type group (4.6±0.9 mm vs 4.2±0.9 mm, p=0.02), and LNE was more likely to occur in the KRAS mutation group (73.3% vs 26.7%, p=0.03). There was no significant difference between the KRAS mutation group and the KRAS wild-type group on the other CT parameters (location, IMV, calcification, ulcer, distant metastasis, tumor shape, enhanced pattern, circumferential extent, CT ratio, and LOT). In the pathological findings, a KRAS mutation was more likely to occur in the middle differentiation group (p=0.03). No significant difference was found between the KRAS mutation group and the KRAS wild-type group in the presence of lymphovascular emboli, signet ring cell, peripheral fat interval infiltration, focal ulcer, lymph node metastasis, and tumor pathological type. With the best cut-off value of 4.07 mm, the AUC of the SRV to predict a KRAS mutation was 0.63 with a sensitivity of 76.2% and a specificity of 48.9%. Conclusion It was feasible to use the diameter of the SRV to predict a KRAS mutation in rectal cancer patients, and LNE also can be regarded as an important clue on preoperative CT images.

Periodic water impoundment and seasonal flood events result in a 30 m water level fluctuation zone (WLFZ) in the Three Gorges Reservoir Region (TGRR), China. In order to assess the occurrence, sources and seasonal variation of airborne carbonaceous pollutants, a total of thirty-nine PM2.5 samples, twenty-two from August 2017 (summer: low water level ~135m) and seventeen from January 2018 (winter: high water level ~175m) were collected consecutively at a rural site in WLFZ in the TGRR. The results showed that OC, EC, char, soot, 16 PAHs and n-alkanes were higher in winter (mean: 9.17 μg/m3, 4.69 μg/m3, 4.25 μg/m3, 0.45 μg/m3, 19.8 ng/m3 and 210 ng/m3, respectively) than in summer (mean: 6.55 μg/m3, 1.70 μg/m3, 1.37 μg/m3, 0.32 μg/m3, 6.13 ng/m3 and 79.1 ng/m3, respectively). Compositional differences suggested air-soil/plant exchange as a source for 2-3-rings PAHs in summer and biomass burning for 4-5-rings in winter. Diagnostic ratios and PCA suggested more vehicular emission for PAHs in summer. Plant waxes contributed 18.2% and 26.2% of the n-alkanes in summer and winter, respectively, implying a relatively greater contribution from petroleum residues. The specific ratios and relative abundance of hopanes and steranes indicated mixed sources from both vehicle exhaust and petroleum residue; and petroleum residues contribute more steranes in summer compared with winter. As revealing basic information on the formation mechanism of carbonaceous aerosols, this study could contribute to a further understanding of their environmental geochemical behavior in the WLFZ of TGRR.

TMPRSS2 is an important membrane-anchored serine protease involved in human prostate cancer progression and metastasis. A serine protease physiologically often comes together with a cognate inhibitor for execution of proteolytically biologic function; however, TMPRSS2’s cognate inhibitor is still elusive. To identify the cognate inhibitor of TMPRSS2, in this study, we applied co-immunoprecipitation and LC/MS/MS analysis and isolated hepatocyte growth factor activator inhibitors (HAIs) to be potential inhibitor candidates for TMPRSS2. Moreover, the recombinant HAI-2 proteins exhibited a better inhibitory effect on TMPRSS2 proteolytic activity than HAI-1, and recombinant HAI-2 proteins had a high affinity to form a complex with TMPRSS2. The immunofluorescence images further showed that TMPRSS2 was co-localized to HAI-2. Both KD1 and KD2 domain of HAI-2 showed comparable inhibitory effects on TMPRSS2 proteolytic activity. In addition, HAI-2 overexpression could suppress the induction effect of TMPRSS2 on pro-HGF activation, extracellular matrix degradation and prostate cancer cell invasion. We further determined that the expression levels of TMPRSS2 were inversely correlated with HAI-2 levels during prostate cancer progression. In orthotopic xenograft animal model, TMPRSS2 overexpression promoted prostate cancer metastasis, and HAI-2 overexpression efficiently blocked TMPRSS2-induced metastasis. In summary, the results together indicate that HAI-2 can function as a cognate inhibitor for TMPRSS2 in human prostate cancer cells and may serve as a potential factor to suppress TMPRSS2-mediated malignancy.

Background Leiomyosarcoma of the inferior vena cava (IVC) is a rare malignant tumour with poor prognosis. Surgical resection is the first line of treatment to achieve the best possible outcome. However, precise preoperative evaluation is essential to guide therapeutic decisions. Here, the preoperative evaluation potential of gadobutrol-enhanced magnetic resonance imaging (MRI) was assessed in the management of a 42-year-old patient with a large IVC mass. Methods The patient first underwent enhanced computed tomography (CT), but the relationship between the left renal vein and the mass in the dilated IVC was ambiguous, and it remained unclear whether the right hepatic vein was invaded by the lesion. To make a precise assessment of the tumour, the patient subsequently underwent high-resolution MRI angiography examination combined with high-concentration contrast medium gadobutrol. Results MRI demonstrated the integrity of the right hepatic vein and the left renal vein. Following a multidisciplinary consultation, a complicated surgery including complete resection of the mass, artificial vessel replacement of IVC, total hepatectomy, and bilateral nephrectomy with liver and kidney auto-transplantation was performed successfully. The surgical plan formulated after reviewing the MRI preoperatively was adhered to the course of the surgery. Postoperative CT re-examination showed that the blood flow of the artificial blood vessel and the right hepatic vein was unobstructed. Histopathological examination confirmed the tumour to be a leiomyosarcoma. Conclusion Preoperative imaging diagnosis and assessment have important implications for the surgical planning of IVC leiomyosarcoma. High-resolution MRI angiography examination with high concentration contrast medium gadobutrol may be of particular benefit in IVC tumours.

Purpose: EGFR tyrosine kinase inhibitors (EGFR-TKI) benefit patients with advanced lung adenocarcinoma (ADC) harboring activating EGFR mutations. We aimed to identify biomarkers to monitor and predict the progression of patients receiving EGFR-TKIs via a comprehensive omic analysis. Experimental Design: We applied quantitative proteomics to generate the TKI resistance–associated pleural effusion (PE) proteome from patients with ADC with or without EGFR-TKI resistance. Candidates were selected from integrated genomic and proteomic datasets. The PE (n = 33) and serum (n = 329) levels of potential biomarkers were validated with ELISAs. Western blotting was applied to detect protein expression in tissues, PEs, and a cell line. Gene knockdown, TKI treatment, and proliferation assays were used to determine EGFR-TKI sensitivity. Progression-free survival (PFS) and overall survival (OS) were assessed to evaluate the prognostic values of the potential biomarkers. Results: Fifteen proteins were identified as potential biomarkers of EGFR-TKI resistance. Cadherin-3 (CDH3) was overexpressed in ADC tissues compared with normal tissues. CDH3 knockdown enhanced EGFR-TKI sensitivity in ADC cells. The PE level of soluble CDH3 (sCDH3) was increased in patients with resistance. The altered sCDH3 serum level reflected the efficacy of EGFR-TKI after 1 month of treatment (n = 43). Baseline sCDH3 was significantly associated with PFS and OS in patients with ADC after EGFR-TKI therapy (n = 76). Moreover, sCDH3 was positively associated with tumor stage in non–small cell lung cancer (n = 272). Conclusions: We provide useful marker candidates for drug resistance studies. sCDH3 is a survival predictor and real-time indicator of treatment efficacy in patients with ADC treated with EGFR-TKIs.

BackgroundHepatocellular carcinoma (HCC) with hilar bile duct tumor thrombus (HBDTT) often mimic hilar cholangiocarcinoma (hilar CC). The purpose of this study is to analyze the Computed Tomography (CT) characteristics of HCC with HBDTT and to identify imaging features to aid its differentiation from hilar CC on enhanced CT.MethodsWe retrospectively identified 58 cases with pathologically proved HCC with HBDTT between 2011 and 2018. Seventy-seven cases of pathologically proven hilar CCs were selected during the same period. The clinical features and CT findings of the two groups were reviewed and compared.ResultsHCC with HBDTTs are more commonly found in men (87.9% vs 63.6%,p = 0.001) with lower age of onset (49.84 vs 58.61 years;p p p p p = 0.001), parenchymal lesion with intraductal lesion (100% vs 18.2%;p p p p p ConclusionsHCC with HBDTTs are often distinguishable from hilar CCs based on washout during portal venous phase without thickened bile duct wall. HBV infection and serum AFP level facilitate the differentiation.

Collagen is an important biomarker of osteoporosis progression. Noninvasive, multispectral, photoacoustic (PA) techniques use pulsed laser light to induce PA signals to facilitate the visualization of chemical components that are strongly related to tissue health. In this study, the feasibility of multi-wavelength PA (MWPA) measurement of the collagen in bone, using the wavelength range of 1300–1800 nm, was investigated. First, the feasibility of this approach for detecting the collagen content of bone was demonstrated by means of numerical simulation. Then, ex vivo experiments were conducted on both animal and human bone specimens with different bone densities using the MWPA method. The relative collagen content was extracted and compared with the results of micro-computed tomography (micro-CT) and histology. The results showed that the “relative collagen content” parameter obtained using the MWPA approach correlated well with the bone volume ratio obtained from micro-CT images and histological analysis results. This study highlights the potential of the proposed PA technique for determining the collagen content of bones as a biomarker for bone health assessment.

BackgroundProgressive overloads of intrahepatic triglycerides are related to metabolic dysregulation of multiple lipid and lipoprotein profiles, but whether similar dose effects are found in each subtype of metabolic associated fatty liver disease (MAFLD) remains unclear. We aimed to characterize the lipid profiles associated with liver fat content (LFC) in MAFLD patients who were overweight, lean/normal weight, or had diabetes.MethodsWe conducted a cross-sectional study enrolling 1,182 consecutive participants (144 non-MAFLD and 1,038 MAFLD) who underwent MRI proton density fat fraction measurement (MRI-PDFF) from 2011 to 2020. Lipid and apolipoprotein profiles, free fatty acid (FFA), liver and metabolism parameters, and anthropometric measurements were also assessed.ResultsMAFLD patients with type 2 diabetes or overweight/obesity had a higher proportion of abnormal lipid and lipoprotein profiles than those who were lean/normal weight. The degree of LFC had a positive correlation with total cholesterol, triglyceride, ApoB, and ApoE in patients with overweight/obesity and type 2 diabetes. In those with overweight/obesity, there were dose–response relationships between moderate-to-severe steatosis and total cholesterol, triglyceride, HDL-c, LDL-c, ApoB, ApoE, and Lp(a). A similar trend was observed for triglyceride in those with type 2 diabetes and for HDL-c in patients who were lean/normal weight (all p for trend ConclusionLFC was associated with lipid profiles, including triglyceride, LDL-c, ApoB, ApoE, and FFA. These relationships were varied by the phenotype of MAFLD according to its diagnostic flow.

Fibrostenosis is a serious complication of Crohn’s disease (CD), affecting approximately one-half of all patients. Surgical resection is the typical clinical end due to ineffective antifibrotic therapy mainly through anti-inflammatory treatment and fibrosis can be reverted only at early stages. Mover, human fibrotic disorders is known to be associated with aging process. Thus, accurate monitoring of the progression of fibrosis is crucial for CD management as well as can be benefit to aging related fibrosis. The excessive deposition of type I collagen (ColI) is the core point in major complications of fibrosis, including that in patients with CD and aging related fibrosis. Therefore, a MR imaging probe (EP-3533) targeted ColI was employed to stage bowel fibrosis in CD using a rat model and to compare its efficiency with the common MR imaging contrast medium gadopentetatedimeglumine (Gd-DTPA). The bowel fibrotic rat model was established with different degrees of bowel fibrosis, were scanned using a 3.0-T MRI scanner with a specialized animal coil. MRI sequence including T1 mapping and T1-weighed imaging were performed before and after injecting the MRI probe (EP-3533 or Gd-DTPA). The T1 relaxation time (T1 value) and change in the contrast-to-noise ratio (ΔCNR) were measured to evaluate bowel fibrosis. Masson’s trichrome staining was performed to determine the severity of fibrosis. EP-3533 offered a better longitudinal relaxivity (r1) with 67.537 L/mmol·s, which was approximately 13 times that of Gd-DTPA. The T1 value on bowel segments was reduced in the images from EP-3533 compared to that from Gd-DTPA (F = 16.478; p < 0.001). Additionally, a better correlation between ΔCNR calculated from EP-3533 imaging and bowel fibrosis (AUC = 0.846) was determined 10 min after enhanced media administration than with Gd-DTPA (AUC = 0.532). The 10th-minute ΔCNR performed using the ColI probe showed the best correlation with the severity of bowel fibrosis (r = 0.538; p = 0.021). Our results demonstrates that targeted MRI probe (EP-3533) supplies a better enhanced effect compared to Gd-DTPA and could be a promising method to evaluate the progression and monitor the therapeutic response of bowel fibrosis.

Background Interleukin (IL)-38, a novel member of the IL-1 family, has been reported to be involved in several diseases associated with viral infection. However, the expression and functional role of IL-38 in acute viral myocarditis (AVMC) have not been investigated. Methods Male BALB/c mice were treated with intraperitoneal (i.p.) injection of coxsackievirus B3 (CVB3) for establishing AVMC models. On day 7 post-injection, the expression of IL-38 and IL-36R (IL-36 receptor) were measured. Mice were then treated with i.p. injection of mouse Anti-IL-38 Antibodies (Abs) for neutralization of IL-38. The survival, bodyweight loss, cardiac function, and myocarditis severity of mice were recorded. The percentages of splenic Th1 and Th17 cells, the expression levels of Th1/Th17-related master transcription factors (T-bet and RORγt) and cytokines were determined by flow cytometry, RT-qPCR, and ELISA, respectively. Cardiac viral replication was further detected. Results The mRNA and protein expression levels of IL-38 in myocardium and serum, as well as cardiac IL-36R mRNA levels were significantly elevated in mice with AVMC. Increased IL-38 levels were negatively correlated with the severity of AVMC. Neutralization of IL-38 exacerbated CVB3-induced AVMC, as verified by the lower survival rate, impaired cardiac function, continuous bodyweight loss, and higher values of HW/BW and cardiac pathological scores. In addition, neutralization of IL-38 suppressed Th1 cells differentiation while promoted Th17 cells differentiation, accompanied by decreased T-bet mRNA expression and increased RORγt expression. Down-regulation of IFN-γ and up-regulation of IL-17, TNF-α, and IL-6 mRNA and protein expression levels in myocardium and serum were also observed in the IL-38 neutralization group. Furthermore, neutralization of IL-38 markedly promoted cardiac viral replication. Conclusions Neutralization of IL-38 exacerbates CVB3-induced AVMC in mice, which may be attributable to the imbalance of Th1/Th17 cells and increased CVB3 replication. Thus, IL-38 can be considered as a potential therapeutic target for AVMC.

ObjectiveAccurate prediction of postoperative recurrence risk of gastric cancer (GC) is critical for individualized precision therapy. We aimed to investigate whether a computed tomography (CT)-based radiomics nomogram can be used as a tool for predicting the local recurrence (LR) of GC after radical resection.Materials and Methods342 patients (194 in the training cohort, 78 in the internal validation cohort, and 70 in the external validation cohort) with pathologically proven GC from two centers were included. Radiomics features were extracted from the preoperative CT imaging. The clinical model, radiomics signature, and radiomics nomogram, which incorporated the radiomics signature and independent clinical risk factors, were developed and verified. Furthermore, the performance of these three models was assessed by using the area under the curve (AUC) of receiver operating characteristic (ROC) curve analysis and decision curve analysis (DCA).ResultsThe radiomics signature, which was comprised of two selected radiomics features, namely, contrast_GLCM and dissimilarity_GLCM, showed better performance than the clinical model in predicting the LR of GC, with AUC values of 0.83 in the training cohort, 0.84 in the internal validation cohort, and 0.73 in the external cohort, respectively. By integrating the independent clinical risk factors (N stage, bile acid duodenogastric reflux and nodular or irregular outer layer of the gastric wall) into the radiomics signature, the radiomics nomogram achieved the highest accuracy in predicting LR, with AUC values of 0.89, 0.89 and 0.80 in the three cohorts, respectively. DCA in the validation cohort showed that radiomics nomogram added more net benefit than the clinical model within the range of 0.01-0.98.ConclusionThe CT-based radiomics nomogram has the potential to predict the LR of GC after radical resection.

The photoacoustic (PA) technique is uniquely positioned for biomedical applications primarily due to its ability to visualize optical absorption contrast in deep tissue at ultrasound resolution. In this work, via both three-dimensional (3D) numerical simulations and in vivo experiments on human subjects, we investigated the possibility of PA measurement of human calcaneus bones in vivo in a non-invasive manner, as well as its feasibility to differentiate osteoporosis patients from normal subjects. The results from the simulations and the experiments both demonstrated that, when one side of the heel is illuminated by laser with light fluence under the ANSI safety limit, the PA signal generated in the human calcaneus bone can be detected by an ultrasonic transducer at the other side of the heel (i.e. transmission mode). Quantitative power spectral analyses of the calcaneus bone PA signals were also conducted, demonstrating that the microarchitectural changes in calcaneus bone due to osteoporosis can be detected, as reflected by enhanced high frequency components in detected PA bone signal. Further statistical analysis of the experimental results from 10 osteoporosis patients and 10 healthy volunteers showed that the weighted frequency as a quantified PA spectral parameter can differentiate the two subject groups with statistical significance.

To investigate the characteristics of dendritic cells (DC) and natural killer cells (NK) in umbilical cord blood of pregnant patients diagnosed with idiopathic fetal growth restriction (IFGR).A prospective study cohort of IFGR patients was established who were in the third trimester (28-36 weeks), with a healthy, pregnant woman cohort selected as controls. Umbilical cord blood was collected.The study included 50 pregnant women in the IFGR group and 50 pregnant women in the healthy, control group. The incidence of SGA in the IFGR group was 52.0%, and the incidence of preterm birth was 18.0%. The incidence of neonatal complications in neonates with live birth in the IFGR group was 12.0%. The birth weight, body length and placental weight of the newborns in the IFGR group were significantly lower than those in the control group (The number and proportion of DC cells in cord blood may not be the key factors affecting the outcomes observed during FGR pregnancies. However, we found the proportion of NK cells in cord blood to be significantly increased, as well as the ratio of CD56dimCD16 + NK to CD56highCD16-NK to be imbalanced, which may be one of the pathogenesis of the pathological pregnancy leading to IFGR.

Background: The consistency in steatosis grading between magnetic resonance imaging-based proton density fat fraction (MRI-PDFF) and controlled attenuation parameter (CAP) before and after treatment remains unclear. This study aimed to compare the diagnostic accuracy of steatosis grading between MRI-PDFF and CAP using liver biopsy as standard and to evaluate the value of monitoring changes in steatosis grading with CAP during follow-up utilizing MRI-PDFF as a reference. Methods: Consecutive patients from a biopsy cohort and a randomized controlled trial were included in this study and classified into 3 groups (the biopsy, orlistat treatment, and routine treatment subgroups). Hepatic steatosis was measured via MRI-PDFF and CAP at baseline and at the 6th month; the accuracy and cutoffs were assessed in the liver biopsy cohort at baseline. Results: A total of 209 consecutive patients were enrolled. MRI-PDFF and CAP showed comparable diagnostic accuracy for detecting pathological steatosis [⩾S1, area under the receiver operating characteristic curve (AUC) = 0.984 and 0.972, respectively]; in contrast, CAP presented significantly lower AUCs in grades S2–3 and S3 (0.820 and 0.815, respectively). The CAP values correlated well with the MRI-PDFF values at baseline and at the 6th month ( r = 0.809 and 0.762, respectively, both p Conclusions: CAP has decreased value for the initial screening of moderate-severe steatosis and is limited in monitoring changes in steatosis during treatment. The confirmation of steatosis grading with MRI-PDFF remains necessary.

In this study, we investigated the utility of native T1 mapping in differentiating between various grades of fibrosis and compared its diagnostic accuracy to magnetization transfer imaging (MTI) in a rat model of CD. Bowel specimens (64) from 46 CD model rats undergoing native T1 mapping and MTI were enrolled. The longitudinal relaxation time (T1 value) and normalized magnetization transfer ratio (MTR) were compared between none-to-mild and moderate-to-severe fibrotic bowel walls confirmed by pathological assessments. The results showed that the correlation between the T1 value and fibrosis (r = 0.438, p &lt, 0.001) was lower than that between the normalized MTR and fibrosis (r = 0.623, p &lt, 0.001). Overall, the T1 values (t = −3.066, p = 0.004) and normalized MTRs (z = 0.081, p &lt, 0.001) in none-to-mild fibrotic bowel walls were lower than those in moderate-to-severe fibrotic bowel walls. The area under the curve (AUC) of the T1 value (AUC = 0.716, p = 0.004) was significantly lower than that of the normalized MTR (AUC = 0.881, p &lt, 0.001) in differentiating moderate-to-severe fibrosis from none-to-mild fibrosis (z = −2.037, p = 0.042). Our results support the view that the T1 value could be a promising imaging biomarker in grading the fibrosis severity of CD. However, the diagnostic performance of native T1 mapping was not superior to MTI.

Cowden syndrome (CS) is a rare, autosomal dominant, multisystem disease related to the mutation of Phosphatase and tensin homolog (PTEN) tumour suppressor gene. It is characterized by the occurrence of multiple hamartomas, mucocutaneous lesions, and is associated with a high risk of malignancies. Lhermitte–Duclos Disease (LDD), or dysplastic cerebellar gangliocytoma, is a rare hamartomatous lesion of the cerebellar cortex with a unique “Tiger Stripe” appearance on Magnetic Resonance Imaging (MRI). Since 1991, LDD has been considered pathognomonic and part of CS. In addition, as almost all adult onset LDD cases were associated with PTEN gene mutations, LDD and CS are both included in PTEN Harmartoma Tumour Syndrome (PHTS). In this article, we report a 48-year-old female patient, who presented with a right cerebellar lesion resulting in hydrocephalus. The histology of the cerebellar lesion confirmed the diagnosis of LDD, and her clinical history is highly suggestive of CS. Due to the high incidence of multisystemic malignancies and other disease, it is important for clinicians to be aware of the association between LDD and CS. Affected patients should be evaluated carefully and screened for cancers accordingly, so as to allow early diagnosis and treatment.

Adaptive immunity and innate immunity have been implicated in the pathogenesis of abdominal aortic aneurysm (AAA), and damage and remodelling in the tunica media are a focus of the aneurysm development. Thus, identification of key immune cells or molecules that might be targets for the treatment of AAA is critical. We characterized the innate immune cells in human AAA tissue specimens by flow cytometry and found that apart from other lymphocytes, many invariant natural killer T (iNKT) cells marked as CD3 and Va24Ja18 had invaded the aortic tissues and were numerous, especially in the tunica media. These infiltrating iNKT cells have a high expression of CD69, indicating a highly active function. We were interested in whether iNKT cells could be the drivers of media damage in AAA. To answer this question, we used an AAA mouse model induced by angiotensin II (Ang II) infusion, which can reproduce the inflammatory response of AAA in mouse, which was confirmed by RNAseq. The results showed that the incidence of AAA was significantly higher after administration of α-galactosylceramide (α-GalCer), a synthetic glycolipid that activates iNKT cells via CD1d, compared with the Ang II-induced AAA alone (61·54% vs 31·82%) in mice. Histopathological and immunofluorescent staining results showed significantly more severe inflammatory infiltration and pathological lesions in the Ang II+α-GalCer treatment group. These results are highly suggestive that activated iNKT cells greatly contribute to AAA development and that the control of the activation state in iNKT cells may represent an important therapeutic strategy for AAA.

Background N6-Methyladenosine (m6A) is the most common RNA modification and regulates RNA splicing, translation, translocation, and stability. Aberrant expression of m6A has been reported in various types of human cancers. m6A RNA modification is dynamically and reversibly mediated by different regulators, including methyltransferase, demethylases, and m6A binding proteins. However, the role of m6A RNA methylation regulators in thyroid cancer remains unknown. The aim of this study is to investigate the effect of the 13 main m6A RNA modification regulators in thyroid carcinoma. Methods We obtained clinical data and RNA sequencing data of 13 m6A RNA methylation regulators from The Cancer Genome Atlas (TCGA) THCA database. We performed consensus clustering to identify the clinical relevance of m6A RNA methylation regulators in thyroid carcinoma. Then we used LASSO Cox regression analysis to generate a prognostic signature based on m6A RNA modification regulator expression. Kyoto Encyclopedia of Genes and Genomes, Gene Ontology and Gene Set Enrichment Analyses were performed to explore differential cellular processes and signaling pathways between the two groups based on risk signature. Results We found that most of the m6A RNA modification regulators are down-regulated in 450 patients with thyroid carcinoma. We derived a three m6A RNA modification regulator genes-based risk signature (FTO, RBM15 and KIAA1429), that is an independent prognostic biomarker in patients with thyroid carcinoma. Moreover, we found that this risk signature could better predict outcome in male than female. Functional research in vitro demonstrated that the m6A RNA methylation regulators involved in the model acted significant role in the proliferation and migration of thyroid cancer cells. Conclusions Our study revealed the influence of m6A RNA methylation regulators on thyroid carcinoma through biological experiments and three-gene prognostic model.

Objective: To investigate the relationship between Dental Porphyromonas Concentration and Esophageal Cancer in Guangdong, China. Methods: A total of 2031 research objects were included from 2016 and follow-up for 6 years, greater than 65 years old, all are from outpatient department with esophageal foreign body sense. Data are retrospectively analyzing in year 2021. There were 43 cases found to developed esophageal cancer, 7 of them are from exposure group, (high dental porphyromonas group) and 36 from control. Two groups of individuals were retrieved from the Guangdong Provincial Hospital database between year 2016 June to 2021 June. Age, gender, race and region are strictly matched. Both of case and the controls are processing through: a. Specimen collection, b. DNA extraction, c. High-throughput sequencing (screening stage), d. Quantitative determination of target bacteria in the samples of the experimental group by Q-PCR, e. Statistical analysis of experimental data. Two sample t-test are using to detect whether have difference on concentration of Dental Porphyromonas between cases and control group. SAS 15 windows version is used as analytic tools. Results: We found that the odds on having Esophageal Cancer from high dental porphyromonas group is 1.23 times greater than controls (OR=1.23). Also, mean of concentration on Dental Porphyromonas in Esophageal Cancer Group (Cases) are statistically higher than Healthy controls, with a mean of 0.0157 in cases versus 0.0025 in controls, which is 6.54 times higher in Esophageal Group, compare with control group, with P

Background: Cutis Verticis Gyrata (CVG) is a rare skin disease caused by overgrowth of the scalp, presenting as cerebriform folds and wrinkles. CVG can be classified into two forms: primary (essential and non-essential) and secondary. The primary non-essential form is often associated with neurological and ophthalmological abnormalities, while the primary essential form occurs without associated comorbidities. Discussion: We report on a rare case of primary essential CVG with a 4-year history of normal-colored scalp skin mass in the parietal-occipital region without symptom in a 34-year-old male patient, retrospectively summarizing his pathological and Computer Tomography (CT) and magnetic resonance imaging (MRI) findings. The major clinical observations on the CT and MR sectional images include a thickened dermis and excessive growth of the scalp, forming the characteristic scalp folds. With the help of CT and MRI Three-dimensional (3D) reconstruction techniques, the characteristic skin changes could be displayed intuitively, providing more evidence for a diagnosis of CVG. At the 5-year followup, there were no obvious changes in the lesion. Conclusion: Based on our observations, we propose that not all patients with primary essential CVG need surgical intervention, and continuous clinical observation should be an appropriate therapy for those in stable condition.

BACKGROUND: The correlation between visceral adipose tissue volume (VATV), hepatic proton-density fat fraction (PDFF), and pancreatic PDFF has been previously studied to predict the presence of type 2 diabetes mellitus (T2DM). This study investigated VATV quantitation in patients with T2DM, prediabetes, and normal glucose tolerance (NGT) using MRI to assess the roles of VATV, hepatic, and pancreatic PDFF in predicting the presence of T2DM. METHODS: Forty-eight patients with a new clinical diagnosis of T2DM (n=15), prediabetes (n=17), or NGT (n=16) were included and underwent abdominal magnetic resonance imaging (MRI) scanning with the iterative decomposition of water and fat with echo asymmetry and least square estimation image quantification (IDEAL-IQ) sequencing. VATV was obtained at the level of the 2(nd) and 3(rd) lumbar vertebral bodies (VATV L2 and VATV L3) where the sum of VATV L2 and VATV L3 (total VATV) were computed, respectively. Also, pancreatic and hepatic fat content was quantified by measuring the PDFF. The receiver operating characteristic (ROC) curve and binary logistics regression model analysis were employed to evaluate their ability to predict the presence of T2DM. RESULTS: The VATV L2, VATV L3, and total VATV values of the T2DM group were significantly higher than the prediabetes and NGT groups (P0.05). The ROC curve showed the areas under the curve for VATV L2, VATV L3, total VATV, hepatic PDFF, and pancreatic PDFF were 0.76, 0.80, 0.80, 0.79, and 0.75, respectively, in predicting the presence of T2DM (P0.05). The binary logistics regression model analysis revealed that only VATV L3 was independently associated with the incidence of T2DM (P=0.01 and OR =1.01). The sensitivity, specificity, and total accuracy were 80.00%, 88.20%, and 84.40%, respectively. CONCLUSIONS: Compared with hepatic PDFF, pancreatic PDFF, VAVT L2, and total VATV, VAVT L3 was the better predictor of T2DM.

Altered brain volume and metabolic variables have been found in subjects with obesity. However, the role of metabolic parameters in gray matter volume (GMV) has been poorly investigated. This study aimed to investigate the relationship between the metabolic parameters and brain volume in subjects with obesity. Thirty-seven subjects with obesity and 39 age and sex matched normal-weight controls were included in this study. Eighteen of the 37 participants who underwent sleeve gastrectomy were included in the longitudinal analysis. Blood samples and high-resolution 3T T1-weighted magnetic resonance images were collected. Metabolic parameters in plasma and GMV were measured. Multiple linear regression analysis showed that gray matter reduction in several cognition-related cortices including right angular gyrus, superior occipital cortex, superior parietal cortex, and cerebellum was related to decreased creatinine, as well as increased triglyceride, HbA1c, and low-density lipoprotein in plasma in subjects with obesity. Weight loss after the surgery induced significant recovery of altered metabolic parameters and decreased gray matter volume. Furthermore, changes in the four metabolic parameters before and after the surgery were associated with changes in gray matter volume. Our results suggest that the gray matter reduction is related to decreased creatinine as well as increased triglyceride, HbA1c, and low-density lipoprotein in plasma in subjects with obesity.

Background Infliximab levels have been reported to be associated with mucosal healing (MH) in Crohn’s disease (CD). However, whether the association differs between postinduction (week 14) and maintenance (week 30) has seldom been investigated. We aimed to analyze the association between serum infliximab trough levels and MH at the 2 different time points. Methods A retrospective study of CD patients treated with infliximab in a tertiary referral center between January 2012 and May 2018 was conducted. MH was defined as absence of ulceration by endoscopy. Correlations between infliximab level and MH were investigated at 2 specific time points, weeks 14 and 30. Results Median infliximab levels were higher in patients with MH than those without at weeks 14 (7.5 vs 1.5 μg/mL; P < 0.001) and 30 (5.9 vs 0.5 μg/mL; P < 0.001). The median levels in patients with MH at week 14 were higher than at week 30 (7.5 vs 5.9 μg/mL; P < 0.05). Multivariate analysis showed that infliximab level was independently associated with MH (both P < 0.001 at weeks 14 and 30). Infliximab level above 4.85 μg/mL and 2.85 μg/mL identified patients with MH at week 14 (area under the curve [AUC], 0.796; P < 0.001) and week 30 (AUC, 0.780; P < 0.001) with 80% specificity. The rates of MH reached a plateau (>85%) when infliximab levels were above 10 and 6 μg/mL at weeks 14 and 30, respectively. Conclusions Infliximab levels correlated with MH at weeks 14 and 30 in CD patients. Higher levels might be required to achieve MH at postinduction than during maintenance treatment.

Angiogenesis is induced immediately after cerebral ischemia and plays a pivotal role in the strategy against ischemic injury. We hypothesized that the coordinated interaction between microvessels and neurons was altered immediately after stroke, and microvessels and neurons would show the temporal specificity of angiogenic gene profiles after cerebral ischemia. Microvessels and neurons were harvested in the ischemic penumbra of rat brain using the PixCell II laser capture microdissection (LCM) instrument. After RNA isolation, T7 and gene-specific primer RNA linear amplification were performed, and angiogenic functional grouping cDNA profiling was analyzed in LCM samples. cDNA microarray results showed there were 35 (36.46%) and 27 (28.13%) genes expression changes in the microvessels, while 25 (26.04%) and 31 (32.29%) genes were changed in the neurons at 2 h and 24 h after cerebral ischemia. Members of growth factors and receptors, cytokines and chemokines, adhesion molecules, matrix proteins, proteases, and inhibitors showed temporal and spatial differentiation in the microvessels and neurons after cerebral ischemia. This finding will help to understand the coordination and interaction between microvessels and neurons, and to elucidate the molecular mechanisms of angiogenesis after brain ischemic injury.

Metabolic brain network, which is based on functional correlation patterns of 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) images, has been widely applied in both basic and clinical neuroscience. Exploring the properties of the metabolic brain network can provide valuable insight to the physiologic and pathologic processes of the brain. Based on the network theory, modular architecture has the ability to limit the spread of local perturbation impact and therefore modular networks are more robust against external damage. However, whether the metabolic brain network has modular architecture remains unknown. Methods 77 rats performed 18F-FDG PET brain imaging. The metabolic brain network was then constructed by measuring interregional metabolic correlation in inter-subject manner. Afterwards, modular architecture of the network was detected by a greedy algorithm. Further, we perturbed the metabolic brain network by inducing focal photothrombotic ischemia in the bilateral motor cortex and then measured the glucose metabolic change of each brain region using FDG-PET. Results A significant modular architecture was found in the metabolic brain network. The network could be divided into four modules which corresponding approximately to executive, learning/memory, visual/auditory and sensorimotor processing functional domains. After inducing the focal ischemia on the bilateral motor cortex, most of the significantly changed brain regions (13 of 17) belong to the sensorimotor module. Conclusion Our results revealed an inherent modular architecture in the metabolic brain network and gave an experimental evidence that the modularity of the metabolism brain network could limit the spread of local perturbation impact.

Genes in the S100 family are abnormally expressed in a variety of tumor cells and are associated with clinical pathology, but their prognostic value in melanoma patients has not yet been fully elucidated. In this study, we extracted and profiled S100 family mRNA expression data and corresponding clinical data from the Gene Expression Omnibus database to analyze how expression of these genes correlates with clinical pathology. Compared with normal skin, S100A1, S100A13, and S100B were expressed at significantly higher levels in melanoma samples. S100A2, S100A7, S100A8, S100A9, S100A10, S100A11, and S100P were all highly expressed in primary melanoma samples but were expressed at low levels in metastatic melanoma, and all of these genes were strongly correlated with each other (P

Immunoscore evaluates the density of CD3+ and CD8+ T cells in both the tumor core and invasive margin. Pretreatment prediction of immunoscore in hepatocellular cancer (HCC) is important for precision immunotherapy. We aimed to develop a radiomics model based on gadolinium-ethoxybenzyl-diethylenetriamine (Gd-EOB-DTPA)-enhanced MRI for pretreatment prediction of immunoscore (0–2 vs. 3–4) in HCC. The study included 207 (training cohort: n = 150; validation cohort: n = 57) HCC patients with hepatectomy who underwent preoperative Gd-EOB-DTPA-enhanced MRI. The volumes of interest enclosing hepatic lesions including intratumoral and peritumoral regions were manually delineated in the hepatobiliary phase of MRI images, from which 1044 quantitative features were extracted and analyzed. Extremely randomized tree method was used to select radiomics features for building radiomics model. Predicting performance in immunoscore was compared among three models: (1) using only intratumoral radiomics features (intratumoral radiomics model); (2) using combined intratumoral and peritumoral radiomics features (combined radiomics model); (3) using clinical data and selected combined radiomics features (combined radiomics-based clinical model). The combined radiomics model showed a better predicting performance in immunoscore than intratumoral radiomics model (AUC, 0.904 (95% CI 0.855–0.953) vs. 0.823 (95% CI 0.747–0.899)). The combined radiomics-based clinical model showed an improvement over the combined radiomics model in predicting immunoscore (AUC, 0·926 (95% CI 0·884–0·967) vs. 0·904 (95% CI 0·855–0·953)), although differences were not statistically significant. Results were confirmed in validation cohort and calibration curves showed good agreement. The MRI-based combined radiomics nomogram is effective in predicting immunoscore in HCC and may help making treatment decisions. • Radiomics obtained from Gd-EOB-DTPA-enhanced MRI help predicting immunoscore in hepatocellular carcinoma. • Combined intratumoral and peritumoral radiomics are superior to intratumoral radiomics only in predicting immunoscore. • We developed a combined clinical and radiomicsnomogram to predict immunoscore in hepatocellular carcinoma.

Although diffusion-weighted imaging (DWI) is reported to be accurate in detecting bowel inflammation in Crohn’s disease (CD), its ability to assess bowel fibrosis remains unclear. This study assessed the role of DWI in the characterization of bowel fibrosis using surgical histopathology as the reference standard. Abdominal DWI was performed before elective surgery in 30 consecutive patients with CD. The apparent diffusion coefficients (ADCs) in pathologic bowel walls were calculated. Region-by-region correlations between DWI and the surgical specimens were performed to determine the histologic degrees of bowel fibrosis and inflammation. ADCs correlated negatively with bowel inflammation (r = − 0.499, p

Ovarian carcinoma is the most lethal type of gynecologic malignancies. Alterations of Notch pathway are prevalent in ovarian carcinogenesis. This study investigated the expression profile and function of delta-like 1 homolog (DLK1), a non-canonical Notch ligand, during ovarian carcinogenesis. Tissue microarray (TMA) consisting of surgically resected samples from 221 patients with ovarian carcinoma was constructed for DLK1 expression. DLK1 overexpression or knockdown was achieved by adenovirus gene delivery to evaluate the effect of DLK1 on the oncogenic behaviors in ovarian cancer cells and in xenografted tumors. TMA analysis revealed that elevated DLK1 expression was correlated with stages, lymph node metastasis and E-cadherin downregulation. Despite no influence on survival among ovarian carcinoma patients, DLK1 overexpression was specially associated with overall survival and progression free survival in high-grade serous carcinoma (HGSC) patients, constituting an independent prognostic factor for these patients. By adenovirus gene delivery, it was found modulation of cellular DLK1 level regulated the tumorigenic behaviors and epithelial-mesenchymal transition (EMT) in vitro and in vivo. Immunohistochemical analysis further showed that DLK1 overexpression resulted in escalated proliferation, angiogenesis, EMT and Notch activities. Application of recombinant DLK1 extracellular domain (rDLK1-EC) recapitulated the tumorigenic behaviors of DLK1 in ovarian cancer cells. By using neutralizing antibody or pharmaceutical inhibitor, blockade of Notch signaling attenuated the tumorigenic behaviors evoked by DLK1 overexpression. The present study indicates that DLK1 overexpression participates in ovarian carcinogenesis through Notch activation and EMT induction. Moreover, DLK1 may constitute a novel diagnostic biomarker and therapeutic target for HGSC.

To date, few studies explore the involvement of endothelial nitric oxide synthase (eNOS) gene variants in uterine cervical cancer. Therefore, we conducted this study to assess the clinical implication of eNOS in cervical carcinogenesis, clinicopathological characteristics and patient survival. One hundred and seventeen patients with cervical invasive cancer and 95 with preinvasive lesions and 330 control women were consecutively enrolled. Real time polymerase chain reaction was used to examine the genotypic distributions of eNOS single nucleotide polymorphisms (SNPs) rs1799983 (894G>T) at the exon 7 region and rs2070744 (-786T>C) at the promoter region. Our results indicated no significant associations among genotypic distributions of eNOS SNPs and patients with cervical invasive cancer and those with preinvasive lesions as well as normal controls. However, cervical cancer patients with genotypes TC/CC in eNOS SNP rs2070744 carried less risk of advanced stage [odds ratios (OR) = 0.30, 95% confidence interval (CI)=0.09-0.97, p=0.036], parametrium invasion (OR=0.16, 95% CI=0.02-0.75, p=0.009) and pelvic lymph node metastasis (OR=0.12, 95% CI=0.01-0.89, p=0.016). In conclusion, although eNOS SNPs rs2070744 and rs1799983 do not display significant associations with cervical carcinogenesis and patient survival, cervical cancer patients with genotypes TC/CC in rs2070744 carry less risk of advanced stage, parametrium invasion and pelvic lymph node metastasis in Taiwan.

Background: Recently, many studies have indicated the potential roles of vitamin D in rheumatoid arthritis (RA). In the present study, the published available GWAS summary data was used to perform two-sample Mendelian randomization (MR) to infer the causal effect between circulating vitamin D levels and RA risk.Methods: Single nucleotide polymorphisms (SNPs) which significantly associated with exposure were selected as instrumental variables from larger-scale genome-wide association study (GWAS). The robust analytical methods including MR Egger, inverse variance weighted (IVW), weighted median and weighted mode were conducted to infer the causal links. Results: The IVW method suggested that there was no causal relationship of genetically predicted circulating vitamin D on RA (Asian: odds ratio (OR)=0.911, 95% confidence interval (CI), 0.542-1.534, P=0.727; European: OR=0.897, 95% CI, 0.633-1.269, P=0.538). MR Egger (Asian: OR=0.937, 95% CI, 0.373-2.352, P=0.895; European: OR=0.853, 95% CI, 0.469-1.553, P=0.639), weighted median (Asian: OR=0.895, 95% CI, 0.499-1.606, P=0.711; European: OR=0.885, 95% CI, 0.620-1.264, P=0.503) and weighted mode (Asian: OR=0.904, 95% CI, 0.515-1.588, P=0.738; European: OR=0.898, 95% CI, 0.618-1.306, P=0.604) demonstrated that vitamin D was not directly related to RA as well. Conclusions: The MR analysis indicates that there is no evidence of causal effect of genetically predicted circulating vitamin D levels on RA risk.

BACKGROUND Hepatocellular carcinoma (HCC) is characterized by dysregulation of the immune microenvironment and the development of chemoresistance. Specifically, expression of the programmed cell death protein 1 (PD-1)/programmed cell death 1 ligand 1 (PD-L1) axis, an immune checkpoint, may lead to tumour immune escape, resulting in disease progression. The latest research shows that tumour immune escape may be caused by the upregulation of PD-L1 mediated by hypoxia-inducible factor-1 alpha (HIF-1α), and simultaneous inhibition of HIF-1α and PD-L1 has the potential to enhance the host’s antitumour immunity. Moreover, inhibition of the PD-1/PD-L1 axis may mitigate tumour chemoresistance. Shuyu pills (SYPs) contain immunity-enhancing and antitumour components, making them a potential HCC treatment. AIM To investigate the efficacy of SYPs for HCC treatment via simultaneous HIF-1α and PD-L1 inhibition and the mechanism involved. METHODS A subcutaneous xenograft tumour model was first established in BALB/c nude mice by the subcutaneous injection of 1 × 107 SMMC-7721 cells. Male mice (male, 5 weeks old; n = 24) were then randomly divided into the following four groups (n = 6): Control (0.9% normal saline), SYP (200 mg/kg), SYP + cisplatin (DDP) (200 mg/kg + 5 mg/kg DDP weekly via intraperitoneal injection), and DDP (5 mg/kg cisplatin weekly via intraperitoneal injection). The dose of saline or SYPs for the indicated mouse groups was 0.2 mL/d via intragastric administration. The tumour volumes and body weights of the mice were measured every 2 d. The mice were euthanized by cervical dislocation after 14 d of continuous treatment, and the xenograft tissues were excised and weighed. Western blot assays were used to measure the protein expression of HIF-1α, PD­1, PD-L1, CD4+ T cells, and CD8+ T cells in HCC tumours from mice. Quantitative reverse transcription polymerase chain reaction was used for real-time quantitative detection of PD-1, PD-L1, and HIF-1α mRNA expression. An immunofluorescence assay was conducted to examine the expression of CD4+ T cells and CD8+ T cells. RESULTS Compared to mice in the control group, those in the SYP and SYP + DDP groups exhibited reduced tumour volumes and tumour weights. Moreover, the protein and mRNA expression levels of the oncogene HIF­1α and that of the negative immunomodulatory factors PD-1 and PD-L1 were decreased in both the SYP and SYP + DDP groups, with the decrease effects being more prominent in the SYP + DDP group than in the SYP group (HIF-1α protein: Control vs SYP, P = 0.0129; control vs SYP + DDP, P = 0.0004; control vs DDP, P = 0.0152, SYP + DDP vs DDP, P = 0.0448; HIF-1α mRNA: control vs SYP, P = 0.0009; control vs SYP + DDP, P < 0.0001; control vs DDP, P = 0.0003, SYP vs SYP + DDP, P = 0.0192. PD-1 protein: Control vs SYP, P = 0.0099; control vs SYP + DDP, P < 0.0001, SPY vs SYP + DDP, P = 0.0009; SYP + DDP vs DDP, P < 0.0001; PD-1 mRNA: control vs SYP, P = 0.0002; control vs SYP + DDP, P < 0.0001; control vs DDP, P = 0.0003, SPY vs SYP + DDP, P = 0.0003; SYP + DDP vs DDP, P = 0.0002. PD-L1 protein: control vs SYP, P < 0.0001; control vs SYP + DDP, P < 0.0001; control vs DDP, P < 0.0001, SPY vs SYP + DDP, P = 0.0040; SYP + DDP vs DDP, P = 0.0010; PD-L1 mRNA: Control vs SYP, P < 0.0001; control vs SYP + DDP, P < 0.0001; control vs DDP, P < 0.0001, SPY vs SYP + DDP, P < 0.0001; SYP + DDP vs DDP, P = 0.0014). Additionally, the quantitative and protein expression levels of CD4+ T cells and CD8+ T cells were simultaneously upregulated in the SYP + DDP group, whereas only the expression of CD4+ T cells was upregulated in the SYP group. (CD4+ T cell quantitative: Control vs SYP + DDP, P < 0.0001, SYP vs SYP + DDP, P = 0.0005; SYP + DDP vs DDP, P = 0.0002. CD4+ T cell protein: Control vs SYP, P = 0.0033; Control vs SYP + DDP, P < 0.0001; Control vs DDP, P = 0.0021, SYP vs SYP + DDP, P = 0.0004; SYP + DDP vs DDP, P = 0.0006. Quantitative CD8+ T cells: Control vs SYP + DDP, P = 0.0013; SYP vs SYP + DDP, P = 0.0347; SYP + DDP vs DDP, P = 0.0043. CD8+ T cell protein: Control vs SYP + DDP, P < 0.0001; SYP vs SYP + DDP, P < 0.0001; SYP + DDP vs DDP, P < 0.0001). Finally, expression of HIF-1α was positively correlated with that of PD-1/PD-L1 and negatively correlated with the expression of CD4+ T cells and CD8+ T cells. CONCLUSION SYPs inhibit immune escape and enhance chemosensitization in HCC via simultaneous inhibition of HIF-1α and PD-L1, thus inhibiting the growth of subcutaneous xenograft HCC tumours.

Background Acute kidney injury (AKI) in pediatric critical care patients is diagnosed using elevated serum creatinine, which occurs only after kidney impairment. There are no treatments other than supportive care for AKI once it has developed, so it is important to identify patients at risk to prevent injury. This study develops a machine learning model to learn pre-disease patterns of physiological measurements and predict pediatric AKI up to 48 h earlier than the currently established diagnostic guidelines. Methods EHR data from 16,863 pediatric critical care patients between 1 month to 21 years of age from three independent institutions were used to develop a single machine learning model for early prediction of creatinine-based AKI using intelligently engineered predictors, such as creatinine rate of change, to automatically assess real-time AKI risk. The primary outcome is prediction of moderate to severe AKI (Stage 2/3), and secondary outcomes are prediction of any AKI (Stage 1/2/3) and requirement of renal replacement therapy (RRT). Predictions generate alerts allowing fast assessment and reduction of AKI risk, such as: “patient has 90% risk of developing AKI in the next 48 h” along with contextual information and suggested response such as “patient on aminoglycosides, suggest check level and review dose and indication”. Results The model was successful in predicting Stage 2/3 AKI prior to detection by conventional criteria with a median lead-time of 30 h at AUROC of 0.89. The model predicted 70% of subsequent RRT episodes, 58% of Stage 2/3 episodes, and 41% of any AKI episodes. The ratio of false to true alerts of any AKI episodes was approximately one-to-one (PPV 47%). Among patients predicted, 79% received potentially nephrotoxic medication after being identified by the model but before development of AKI. Conclusions As the first multi-center validated AKI prediction model for all pediatric critical care patients, the machine learning model described in this study accurately predicts moderate to severe AKI up to 48 h in advance of AKI onset. The model may improve outcome of pediatric AKI by providing early alerting and actionable feedback, potentially preventing or reducing AKI by implementing early measures such as medication adjustment.

The circadian clock is an endogenous timekeeper system that controls and optimizes biological processes, which are consistent with a master circadian clock and peripheral clocks and are controlled by various genes. Notably, the disruption of circadian clock genes has been identified to affect a wide range of ailments, including cancers. The cancer-immunity cycle is composed of seven major steps, namely cancer cell antigen release and presentation, priming and activation of effector immunity cells, trafficking, and infiltration of immunity to tumors, and elimination of cancer cells. Existing evidence indicates that the circadian clock functions as a gate that govern many aspects of the cancer-immunity cycle. In this review, we highlight the importance of the circadian clock during tumorigenesis, and discuss the potential role of the circadian clock in the cancer-immunity cycle. A comprehensive understanding of the regulatory function of the circadian clock in the cancer-immunity cycle holds promise in developing new strategies for the treatment of cancer. Video Abstract Supplementary Information The online version contains supplementary material available at 10.1186/s12964-021-00721-2.

BackgroundPrevious studies demonstrated a promising prognosis in advanced hepatocellular carcinoma (HCC) patients who underwent surgery, yet a consensus of which population would benefit most from surgery is still unreached.MethodA total of 496 advanced HCC patients who initially underwent liver resection were consecutively collected. Least absolute shrinkage and selection operator (LASSO) regression was performed to select significant pre-operative factors for recurrence-free survival (RFS). A prognostic score constructed from these factors was used to divide patients into different risk groups. Survivals were compared between groups with log-rank test. The area under curves (AUC) of the time-dependent receiver operating characteristics was used to evaluate the predictive accuracy of prognostic score.ResultFor the entire cohort, the median overall survival (OS) was 23.0 months and the median RFS was 12.1 months. Patients were divided into two risk groups according to the prognostic score constructed with ALBI score, tumor size, tumor-invaded liver segments, gamma-glutamyl transpeptidase, alpha fetoprotein, and portal vein tumor thrombus stage. The median RFS of the low-risk group was significantly longer than that of the high-risk group in both the training (10.1 vs 2.9 months, PP=0.002). The AUCs of the prognostic score in predicting survival were 0.70 to 0.71 in the training group and 0.71 to 0.72 in the validation group.ConclusionSurgery could provide promising survival for HCC patients at an advanced stage. Our developed pre-operative prognostic score is effective in identifying advanced-stage HCC patients with better survival benefit for surgery.

BACKGROUND & AIMS: No reliable method for evaluating intestinal fibrosis in Crohn’s disease (CD) exists; therefore, we developed a computed-tomography enterography (CTE)–based radiomic model (RM) for characterizing intestinal fibrosis in CD. METHODS: This retrospective multicenter study included 167 CD patients with 212 bowel lesions (training, 98 lesions; test, 114 lesions) who underwent preoperative CTE and bowel resection at 1 of the 3 tertiary referral centers from January 2014 through June 2020. Bowel fibrosis was histologically classified as none–mild or moderate–severe. In the training cohort, 1454 radiomic features were extracted from venous-phase CTE and a machine learning–based RM was developed based on the reproducible features using logistic regression. The RM was validated in an independent external test cohort recruited from 3 centers. The diagnostic performance of RM was compared with 2 radiologists’ visual interpretation of CTE using receiver operating characteristic (ROC) curve analysis. RESULTS: In the training cohort, the area under the ROC curve (AUC) of RM for distinguishing moderate–severe from none–intestinal fibrosis was 0.888 (95% confidence interval [CI], 0.818–0.957). In the test cohort, the RM showed robust performance across 3 centers with an AUC of 0.816 (95% CI, 0.706–0.926), 0.724 (95% CI, 0.526–0.923), and 0.750 (95% CI, 0.560–0.940), respectively. Moreover, the RM was more accurate than visual interpretations by either radiologist (radiologist 1, AUC = 0.554; radiologist 2, AUC = 0.598; both, P < .001) in the test cohort. Decision curve analysis showed that the RM provided a better net benefit to predicting intestinal fibrosis than the radiologists. CONCLUSIONS: A CTE-based RM allows for accurate characterization of intestinal fibrosis in CD.

Background Transarterial chemoembolization (TACE) is the standard treatment for intermediate-stage hepatocellular carcinoma (HCC). It is unknown whether conventional TACE (cTACE) should be continued or abandoned after initial nonresponse for intermediate-stage HCC. The optimal number of sessions before abandoning cTACE remains debated. Purpose To define the number of sessions that patients who do not respond to treatment (hereafter, nonresponders, with stable disease [SD] or progressive disease [PD]) should undergo before abandoning cTACE. Materials and Methods Patients with intermediate-stage HCC and Child-Pugh A liver function who underwent consecutive cTACE sessions between January 2005 and December 2012 were retrospectively included from three centers. Radiologic response rate to each session and its correlation with overall survival were evaluated. Response was assessed by modified Response Evaluation Criteria in Solid Tumors. A nomogram constructed by using tumor size, tumor capsule, and α-fetoprotein to predict patients who responded to treatment (hereafter, responders) was validated with sensitivity and specificity. Results This study evaluated 4154 patients (mean age, 58 years ± 6 [standard deviation]; 3777 men; primary cohort, 3442 patients [mean age, 58 years ± 6; 3129 men]; validation cohort, 712 patients [mean age, 58 years ± 7; 648 men]). Response rate to first cTACE was 35.6% (1227 of 3442, primary cohort) and 36.7% (261 of 712, validation cohort). For patients with SD who were nonresponders to first cTACE, the response rates after second cTACE were 46.1% (719 of 1560) and 48.4% (147 of 304); for patients with SD who were nonresponders to the second cTACE session, the response rates after the third cTACE session were 58.3% (591 of 1014) and 48.5% (98 of 202). For patients with SD who were nonresponders to third, fourth, and fifth cTACE sessions, response rates after fourth, fifth, and sixth cTACE sessions were less than 10%. All response rates in patients with PD who were nonresponders to the next cTACE were less than 5%. Responders to first, second, and third cTACE had higher 5-year overall survival than nonresponders (all P < .001) but responders to the fourth cTACE did not (P = .21). The sensitivity and specificity of a nomogram predicted responders to third cTACE: 75.0% and 79.4% (internal validation) and 78.6% and 87.0% (external validation), respectively. Conclusion Three sessions were recommended before abandoning conventional transarterial embolization (cTACE) for intermediate-stage hepatocellular carcinoma. The nomogram developed in this study identified responders to third cTACE. © RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Georgiades in this issue.