Development and Validation of a Deep Learning Model to Reduce the Interference of Rectal Artifacts in MRI-based Prostate Cancer Diagnosis.

Purpose To develop an MRI-based model for clinically significant prostate cancer (csPCa) diagnosis that can resist rectal artifact interference. Materials and Methods This retrospective study included 2203 male patients with prostate lesions who underwent biparametric MRI and biopsy between January 2019 and June 2023. Targeted adversarial training with proprietary adversarial samples (TPAS) strategy was proposed to enhance model resistance against rectal artifacts. The automated csPCa diagnostic models trained with and without TPAS were compared using multicenter validation datasets. The impact of rectal artifacts on the diagnostic performance of each model at the patient and lesion levels was compared using the area under the receiver operating characteristic curve (AUC) and the area under the precision-recall curve (AUPRC). The AUC between models was compared using the DeLong test, and the AUPRC was compared using the bootstrap method. Results The TPAS model exhibited diagnostic performance improvements of 6% at the patient level (AUC: 0.87 vs 0.81, P < .001) and 7% at the lesion level (AUPRC: 0.84 vs 0.77, P = .007) compared with the control model. The TPAS model demonstrated less performance decline in the presence of rectal artifact-pattern adversarial noise than the control model (ΔAUC: -17% vs -19%, ΔAUPRC: -18% vs -21%). The TPAS model performed better than the control model in patients with moderate (AUC: 0.79 vs 0.73, AUPRC: 0.68 vs 0.61) and severe (AUC: 0.75 vs 0.57, AUPRC: 0.69 vs 0.59) artifacts. Conclusion This study demonstrates that the TPAS model can reduce rectal artifact interference in MRI-based csPCa diagnosis, thereby improving its performance in clinical applications. Keywords: MR-Diffusion-weighted Imaging, Urinary, Prostate, Comparative Studies, Diagnosis, Transfer Learning Clinical trial registration no. ChiCTR23000069832 Supplemental material is available for this article. Published under a CC BY 4.0 license.

Iron homeostasis imbalance and ferroptosis in brain diseases.

Brain iron homeostasis is maintained through the normal function of blood-brain barrier and iron regulation at the systemic and cellular levels, which is fundamental to normal brain function. Excess iron can catalyze the generation of free radicals through Fenton reactions due to its dual redox state, thus causing oxidative stress. Numerous evidence has indicated brain diseases, especially stroke and neurodegenerative diseases, are closely related to the mechanism of iron homeostasis imbalance in the brain. For one thing, brain diseases promote brain iron accumulation. For another, iron accumulation amplifies damage to the nervous system and exacerbates patients' outcomes. In addition, iron accumulation triggers ferroptosis, a newly discovered iron-dependent type of programmed cell death, which is closely related to neurodegeneration and has received wide attention in recent years. In this context, we outline the mechanism of a normal brain iron metabolism and focus on the current mechanism of the iron homeostasis imbalance in stroke, Alzheimer's disease, and Parkinson's disease. Meanwhile, we also discuss the mechanism of ferroptosis and simultaneously enumerate the newly discovered drugs for iron chelators and ferroptosis inhibitors.

Automated deep-learning system in the assessment of MRI-visible prostate cancer: comparison of advanced zoomed diffusion-weighted imaging and conventional technique.

BACKGROUND: Deep-learning-based computer-aided diagnosis (DL-CAD) systems using MRI for prostate cancer (PCa) detection have demonstrated good performance. Nevertheless, DL-CAD systems are vulnerable to high heterogeneities in DWI, which can interfere with DL-CAD assessments and impair performance. This study aims to compare PCa detection of DL-CAD between zoomed-field-of-view echo-planar DWI (z-DWI) and full-field-of-view DWI (f-DWI) and find the risk factors affecting DL-CAD diagnostic efficiency. METHODS: This retrospective study enrolled 354 consecutive participants who underwent MRI including T2WI, f-DWI, and z-DWI because of clinically suspected PCa. A DL-CAD was used to compare the performance of f-DWI and z-DWI both on a patient level and lesion level. We used the area under the curve (AUC) of receiver operating characteristics analysis and alternative free-response receiver operating characteristics analysis to compare the performances of DL-CAD using f- DWI and z-DWI. The risk factors affecting the DL-CAD were analyzed using logistic regression analyses. P values less than 0.05 were considered statistically significant. RESULTS: DL-CAD with z-DWI had a significantly better overall accuracy than that with f-DWI both on patient level and lesion level (AUCpatient: 0.89 vs. 0.86; AUClesion: 0.86 vs. 0.76; P < .001). The contrast-to-noise ratio (CNR) of lesions in DWI was an independent risk factor of false positives (odds ratio [OR] = 1.12; P < .001). Rectal susceptibility artifacts, lesion diameter, and apparent diffusion coefficients (ADC) were independent risk factors of both false positives (ORrectal susceptibility artifact = 5.46; ORdiameter, = 1.12; ORADC = 0.998; all P < .001) and false negatives (ORrectal susceptibility artifact = 3.31; ORdiameter = 0.82; ORADC = 1.007; all P ≤ .03) of DL-CAD. CONCLUSIONS: Z-DWI has potential to improve the detection performance of a prostate MRI based DL-CAD. TRIAL REGISTRATION: ChiCTR, NO. ChiCTR2100041834 . Registered 7 January 2021.

Adversarial training for prostate cancer classification using magnetic resonance imaging.

Background: To use adversarial training to increase the generalizability and diagnostic accuracy of deep learning models for prostate cancer diagnosis. Methods: This multicenter study retrospectively included 396 prostate cancer patients who underwent magnetic resonance imaging (development set, 297 patients from Shanghai Jiao Tong University Affiliated Sixth People's Hospital and Eighth People's Hospital; test set, 99 patients from Renmin Hospital of Wuhan University). Two binary classification deep learning models for clinically significant prostate cancer classification [PM1, pretraining Visual Geometry Group network (VGGNet)-16-based model 1; PM2, pretraining residual network (ResNet)-50-based model 2] and two multiclass classification deep learning models for prostate cancer grading (PM3, pretraining VGGNet-16-based model 3; PM4: pretraining ResNet-50-based model 4) were built using apparent diffusion coefficient and T2-weighted images. These models were then retrained with adversarial examples starting from the initial random model parameters (AM1, adversarial training VGGNet-16 model 1; AM2, adversarial training ResNet-50 model 2; AM3, adversarial training VGGNet-16 model 3; AM4, adversarial training ResNet-50 model 4, respectively). To verify whether adversarial training can improve the diagnostic model's effectiveness, we compared the diagnostic performance of the deep learning methods before and after adversarial training. Receiver operating characteristic curve analysis was performed to evaluate significant prostate cancer classification models. Differences in areas under the curve (AUCs) were compared using Delong's tests. The quadratic weighted kappa score was used to verify the PCa grading models. Results: AM1 and AM2 had significantly higher AUCs than PM1 and PM2 in the internal validation dataset (0.84 vs. 0.89 and 0.83 vs. 0.87) and test dataset (0.73 vs. 0.86 and 0.72 vs. 0.82). AM3 and AM4 showed higher κ values than PM3 and PM4 in the internal validation dataset {0.266 [95% confidence interval (CI): 0.152-0.379] vs. 0.292 (95% CI: 0.178-0.405) and 0.254 (95% CI: 0.159-0.390) vs. 0.279 (95% CI: 0.163-0.396)} and test set [0.196 (95% CI: 0.029-0.362) vs. 0.268 (95% CI: 0.109-0.427) and 0.183 (95% CI: 0.015-0.351) vs. 0.228 (95% CI: 0.068-0.389)]. Conclusions: Using adversarial examples to train prostate cancer classification deep learning models can improve their generalizability and classification abilities.

Thin-slab maximum intensity projection of CT angiography for collateral score and clot burden score evaluation: comparison with conventional CT angiography.

BACKGROUND: This study aimed to exam the effects of thin-slab maximum intensity projection (TS-MIP) of computed tomography angiography (CTA) for collateral score (CS) and clot burden score (CBS) evaluation in patients with large-vessel-occlusion (LVO) stroke in the anterior circulation. METHODS: Of 241 consecutive patients with LVO stroke admitted to our center between August 2015 and June 2020, 187 patients were enrolled. CS and CBS were evaluated on conventional CTA and TS-MIP separately. Outcome at 90 days was classified as good if modified Rankin scale (mRS) was ≤2 and as poor if mRS was >2. The correlations between CS and CBS and clinical outcomes were assessed. Receiver operating characteristic (ROC) curve analysis was used to determine the diagnostic values of CS and CBS. Multivariate logistic regression analysis was performed to identify the independent predictors of 90-day good clinical outcomes. RESULTS: The correlation coefficient for clinical outcomes was significantly better for CS based on TS-MIP than that based on conventional CTA (-0.444 vs. -0.285, P=0.039); no significant difference was found in the CBS evaluation (TS-MIP: -0.356 vs. conventional CTA: -0.320, P=0.348). For predicting good clinical outcomes, TS-MIP-based CS was associated with larger area under the curve (AUC) (0.709 vs. 0.609, P=0.004) and higher sensitivity (69.1% vs. 42.0%, P=0.001) than CS based on CTA. In multivariable logistic regression analysis, the factors independently associated with good outcomes were National Institutes of Health Stroke Scale (NIHSS) score at admission (OR =1.147; P<0.001), TS-MIP-based CS (OR =0.326; P<0.001), final modified treatment in cerebral infarction (mTICI) score of 2b/3 (OR =0.098; P<0.001), and hemorrhagic transformation (OR =3.662; P<0.001). CONCLUSIONS: TS-MIP-CTA is superior to conventional CTA for evaluation CS and CBS, and TS-MIP-based CS may be a useful predictor of clinical outcome.

Synthesizing High-b-Value Diffusion-weighted Imaging of the Prostate Using Generative Adversarial Networks.

PURPOSE: To develop and evaluate a diffusion-weighted imaging (DWI) deep learning framework based on the generative adversarial network (GAN) to generate synthetic high-b-value (b =1500 sec/mm2) DWI (SYNb1500) sets from acquired standard-b-value (b = 800 sec/mm2) DWI (ACQb800) and acquired standard-b-value (b = 1000 sec/mm2) DWI (ACQb1000) sets. MATERIALS AND METHODS: This retrospective multicenter study included 395 patients who underwent prostate multiparametric MRI. This cohort was split into internal training (96 patients) and external testing (299 patients) datasets. To create SYNb1500 sets from ACQb800 and ACQb1000 sets, a deep learning model based on GAN (M0) was developed by using the internal dataset. M0 was trained and compared with a conventional model based on the cycle GAN (Mcyc). M0 was further optimized by using denoising and edge-enhancement techniques (optimized version of the M0 [Opt-M0]). The SYNb1500 sets were synthesized by using the M0 and the Opt-M0 were synthesized by using ACQb800 and ACQb1000 sets from the external testing dataset. For comparison, traditional calculated (b =1500 sec/mm2) DWI (CALb1500) sets were also obtained. Reader ratings for image quality and prostate cancer detection were performed on the acquired high-b-value (b = 1500 sec/mm2) DWI (ACQb1500), CALb1500, and SYNb1500 sets and the SYNb1500 set generated by the Opt-M0 (Opt-SYNb1500). Wilcoxon signed rank tests were used to compare the readers' scores. A multiple-reader multiple-case receiver operating characteristic curve was used to compare the diagnostic utility of each DWI set. RESULTS: When compared with the Mcyc, the M0 yielded a lower mean squared difference and higher mean scores for the peak signal-to-noise ratio, structural similarity, and feature similarity (P < .001 for all). Opt-SYNb1500 resulted in significantly better image quality (P ≤ .001 for all) and a higher mean area under the curve than ACQb1500 and CALb1500 (P ≤ .042 for all). CONCLUSION: A deep learning framework based on GAN is a promising method to synthesize realistic high-b-value DWI sets with good image quality and accuracy in prostate cancer detection.Keywords: Prostate Cancer, Abdomen/GI, Diffusion-weighted Imaging, Deep Learning Framework, High b Value, Generative Adversarial Networks© RSNA, 2021 Supplemental material is available for this article.

Better lesion conspicuity translates into improved prostate cancer detection: comparison of non-parallel-transmission-zoomed-DWI with conventional-DWI.

PURPOSE: To compare advanced non-parallel transmission zoomed diffusion-weighted imaging (nonPTX zoom-DWI) to conventional DWI (conv-DWI) for the assessment of prostate cancer (PCa). METHODS: This retrospective study included 98 patients who underwent conv-DWI, nonPTX zoom-DWI, and T2-weighted imaging of the prostate. The image qualities of the two DWI sets, including the distortion of the prostate and the existence of artifacts, were evaluated. To compare the overall PCa and clinically important PCa (ciPCa) detection ability between the sets, lesions were scored using the Prostate Imaging Reporting and Data System (PI-RADS) version 2. Apparent diffusion coefficient (ADC) values of the lesions were also measured and compared. The Mann-Whitney U test was used to compare continuous variables, and the χ2 test was used to compare categorical variables. Two-sided P values of < 0.05 were considered significant. RESULTS: Non-PTX zoom-DWI yielded significantly better image quality and image analysis reproducibility than conv-DWI (all P < 0.001). Compared with conv-ADC, nonPTX zoom-ADC showed slightly better detection performance for overall PCa (AUC: 0.827 vs. 0.797; P = 0.55) and ciPCa (AUC: 0.822 vs. 0.749; P = 0.58). At a PI-RADS score of 4 as the cutoff value for PCa prediction, nonPTX zoom-DWI showed significantly higher diagnostic efficiency for overall PCa detection (sensitivity: 87.9% vs. 72.4%; specificity: 87.5% vs. 77.5%; both P < 0.05) and ciPCa detection (sensitivity: 86.3% vs. 74.5%; specificity: 72.3% vs. 63.8%; both P ≤ 0.001). CONCLUSION: Non-PTX zoom-DWI yields better image quality and higher PCa detection performance than Conv-DWI.

Upregulating CXCR7 accelerates endothelial progenitor cell-mediated endothelial repair by activating Akt/Keap-1/Nrf2 signaling in diabetes mellitus.

BACKGROUND: Endothelial progenitor cell (EPC) dysfunction contributes to vascular disease in diabetes mellitus. However, the molecular mechanism underlying EPC dysfunction and its contribution to delayed reendothelialization in diabetes mellitus remain unclear. Our study aimed to illustrate the potential molecular mechanism underlying diabetic EPC dysfunction in vivo and in vitro. Furthermore, we assessed the effect of EPC transplantation on endothelial regeneration in diabetic rats. METHODS: Late outgrowth EPCs were isolated from the bone marrow of rats for in vivo and in vitro studies. In vitro functional assays and Western blotting were conducted to reveal the association between C-X-C chemokine receptor type 7 (CXCR7) expression and diabetic EPC dysfunction. To confirm the association between cellular CXCR7 levels and EPC function, CXCR7 expression in EPCs was upregulated and downregulated via lentiviral transduction and RNA interference, respectively. Western blotting was used to reveal the potential molecular mechanism by which the Stromal-Derived Factor-1 (SDF-1)/CXCR7 axis regulates EPC function. To elucidate the role of the SDF-1/CXCR7 axis in EPC-mediated endothelial regeneration, a carotid artery injury model was established in diabetic rats. After the model was established, saline-treated, diabetic, normal, or CXCR7-primed EPCs were injected via the tail vein. RESULTS: Diabetic EPC dysfunction was associated with decreased CXCR7 expression. Furthermore, EPC dysfunction was mimicked by knockdown of CXCR7 in normal EPCs. However, upregulating CXCR7 expression reversed the dysfunction of diabetic EPCs. The SDF-1/CXCR7 axis positively regulated EPC function by activating the AKT-associated Kelch-like ECH-associated protein 1 (keap-1)/nuclear factor erythroid 2-related factor 2 (Nrf2) axis, which was reversed by blockade of AKT and Nrf2. Transplantation of CXCR7-EPCs accelerated endothelial repair and attenuated neointimal hyperplasia in diabetes mellitus more significantly than transplantation of diabetic or normal EPCs. However, the therapeutic effect of CXCR7-EPC transplantation on endothelial regeneration was reversed by knockdown of Nrf2 expression. CONCLUSIONS: Dysfunction of diabetic EPCs is associated with decreased CXCR7 expression. Furthermore, the SDF-1/CXCR7 axis positively regulates EPC function by activating the AKT/keap-1/Nrf2 axis. CXCR7-primed EPCs might be useful for endothelial regeneration in diabetes-associated vascular disease.

Comparative Study on Iron Content Detection by Energy Spectral CT and MRI in MDS Patients.

Objective: The purpose of this study was to identify the difference between dual energy spectral computed tomography (DECT) and magnetic resonance imaging (MRI) used to detect liver/cardiac iron content in Myelodysplastic syndrome (MDS) patients with differently adjusted serum ferritin (ASF) levels. Method: Liver and cardiac iron content were detected by DECT and MRI. Patients were divided into different subgroups according to the level of ASF. The receiver operating characteristic curve (ROC) analysis was applied in each subgroup. The correlation between iron content detected by DECT/MRI and ASF was analyzed in each subgroup. Result: ROC curves showed that liver virtual iron content (LVIC) Az was significantly less than liver iron concentration (LIC) Az in the subgroup with ASF < 1,000 ng/ml. There was no significant difference between LVIC Az and LIC Az in the subgroup with 1,000 ≤ ASF < 2,500 ng/ml and 2,500 ≤ ASF < 5,000 ng/ml. LVIC Az was significantly higher than LIC Az in the subgroup with ASF <5,000 and 5,000 ≤ ASF ng/ml. In patients undergoing DECT and MRI examination on the same day, ASF was significantly correlated with LVIC, whereas no significant correlation was observed between ASF and LIC. After removing the data of ASF > 5,000 mg/L in LIC, LIC became correlated with ASF. There was no significant difference between the subgroup with 2,500 ≤ ASF < 5,000 ng/ml and 5,000 ng/ml ≤ ASF in LIC expression. Furthermore, both LIC and liver VIC had significant correlations with ASF in patients with ASF < 2,500 ng/ml, while LVIC was still correlated with ASF, LIC was not correlated with ASF in patients with 2,500 ng/ml ≤ ASF. Moreover, neither cardiac VIC nor myocardial iron content (MIC) were correlated with ASF in these subgroups. Conclusion: MRI and DECT were complementary to each other in liver iron detection. In MDS patients with high iron content, such as ASF ≥ 5,000 ng/ml, DECT was more reliable than the MRI in the assessment of iron content. But in patients with low iron content, such as ASF < 1,000 ng/ml, MRI is more reliable than DECT. Therefore, for the sake of more accurately evaluating the iron content, the appropriate detection method can be selected according to ASF.

CGM for insulinoma screening: a prospective and observational case-control study.

Insulin release index (IRI) based on 72-h fasting test has been used for the definitive diagnosis of insulinoma; however, hospitalization and subsequent costs contribute to the disadvantage of IRI. Therefore, a simple and cost-effective screening procedure for the diagnosis of insulinoma for outpatients are crucially needed. Continuous glucose monitoring (CGM) has been widely used for monitoring high level of glucose in diabetic patients. The aim of the study is to determine the potential contribution or implementation of CGM in the screening of the insulinoma. We performed a single-center prospective study with the demographics and laboratory data including 28 patients with the pathological diagnosis of insulinoma and 25 patients with functional hypoglycemia as control group. The analysis showed that areas under the receiver operating characteristic (ROC) curve of coefficient of variation (CV) was 0.914. The CV cutoff point was 19% with the Youden 62.1%, the corresponding sensitivity and specificity were 82.1 and 80%, respectively. In patients with CV greater than the median, more than 60% of insulinomas were located in the head of the pancreas; most Ki-67 values were more than 2% and when compared with the group with CV smaller than the median, the average tumor size was 2.7 times larger. In conclusion, CGM can be used as a valuable tool in not only monitoring high glucose levels in diabetic patients but also identifying the etiology of insulinoma. CV greater than 19% can be highly effective for the screening of insulinoma in outpatients.

Analysis of the influencing factors related to liver and cardiac iron overload in MDS patients detected by MRI in the real world.

OBJECTIVES: We aim to explore and analyze the related influencing factors of liver and cardiac iron overload in MDS patients detected by magnetic resonance imaging (MRI). METHODS: We have detected cardiac T2* and liver T2* by MRI in 105 MDS patients. Among them, 20 patients accepted MRI examination before and after iron chelation therapy (ICT). Results: We found that adjusted ferritin (ASF) was significantly correlated with liver T2* and cardiac T2*. RBC transfusion volume, brain natriuretic peptide (BNP) and age were the related factors of cardiac T2*, while RBC transfusion volume and erythropoietin (EPO) were related factors of liver T2*. After ICT, the changes of ASF and liver T2* were earlier than cardiac T2*. Chronic hepatitis but virus copy normal's has no significant effect on liver iron deposition. CONCLUSION: These results showed special attention should be paid to these related influencing factors of liver and cardiac T2* expression when we evaluated iron overload and detected the efficacy of ICT in MDS patients.

AMD3100 and SDF­1 regulate cellular functions of endothelial progenitor cells and accelerate endothelial regeneration in a rat carotid artery injury model.

The present study was conducted to assess the effects of AMD3100 and stromal cell-derived factor 1 (SDF-1) on cellular functions and endothelial regeneration of endothelial progenitor cells (EPCs). The cell proliferation and adhesion capacity of EPCs were evaluated in vitro following treatment with AMD3100 and SDF­1 using a Cell Counting Kit­8 assay. Furthermore, the expression levels of C­X­C motif chemokine receptor 4 (CXCR4) and C­X­C motif chemokine receptor 7 (CXCR7) were detected before and after treatment with AMD3100 and SDF­1 to elucidate their possible role in regulating the cellular function of EPCs. A rat carotid artery injury model was established to assess the influences of AMD3100 and SDF­1 on endothelial regeneration. AMD3100 reduced the proliferation and adhesion capacity of EPCs to fibronectin (FN), whereas it increased the adhesion capacity of EPCs to human umbilical vein endothelial cells (HUVECs). However, SDF­1 stimulated the proliferation and cell adhesion capacity of EPCs to HUVECs and FN. Additionally, the expression levels of CXCR7 but not CXCR4 were upregulated following AMD3100 treatment, whereas the expression levels of both CXCR4 and CXCR7 were upregulated after SDF­1 treatment. In vivo results demonstrated that AMD3100 increased the number of EPCs in the peripheral blood and facilitated endothelial repair at 7 days after treatment. However, local administration of SDF­1 alone did not enhance reendothelialization 7 and 14 days after treatment. Importantly, the combination of AMD3100 with SDF­1 exhibited superior therapeutic effects compared with AMD3100 treatment alone, accelerated reendothelialization 7 days after treatment, and attenuated neointimal hyperplasia at day 7 and 14 by recruiting more EPCs to the injury site. In conclusion, AMD3100 could positively regulate the adhesion capacity of EPCs to HUVECs via elevation of the expression levels of CXCR7 but not CXCR4, whereas SDF­1 could stimulate the proliferation and adhesion capacity of EPCs to FN and HUVECs by elevating the expression levels of CXCR4 and CXCR7. AMD3100 combined with SDF­1 outperformed AMD3100 alone, promoted early reendothelialization and inhibited neointimal hyperplasia, indicating that early reendothelialization attenuated neointimal hypoplasia following endothelial injury.

Plerixafor stimulates adhesive activity and endothelial regeneration of endothelial progenitor cells via elevating CXCR7 expression.

AIMS: To assess the effects of plerixafor on function and endothelial regeneration of endothelial progenitor cells (EPCs). METHODS: The proliferation and adhesion capacity of EPCs were evaluated in vitro. Furthermore, the expression levels of CXC chemokine receptor-7 (CXCR7) were detected before and after treatment with plerixafor. The CXCR7 expression of EPCs was knocked-down by RNA interference to evaluate the role of CXCR7 in regulating function of EPCs. A rat carotid artery injury model was established to assess the influences of plerixafor on endothelial regeneration. RESULTS: Plerixafor stimulated adhesion capacity of EPCs, associating with upregulation of CXCR7 and activation of LFA-1 and VLA-4 molecules. Knockdown of CXCR7 slightly impaired proliferation capacity but significantly attenuated adhesion capacity of EPCs. Plerixafor facilitated endothelial repair at 7 days, while reduced neointimal hyperplasia at 7 and 14 days via recruiting more EPCs participating in endothelial reparation. CONCLUSIONS: Plerixafor can positively regulate adhesion capacity of EPCs to HUVECs via elevating the expression level of CXCR7 and stimulating LFA-1 and VLA-4 molecules activation. Treatment with plerixafor accelerated re-endothelialization and inhibited neointimal hyperplasia after endoth elial injury, indicating that it can to be used for endothelial regeneration.

Index of Plantar Pressure Alters with Prolonged Diabetes Duration.

INTRODUCTION: Diabetic foot ulcers develop with deviations in the distribution of plantar pressure. It is difficult to interpret any alteration in plantar pressure under different conditions of type 2 diabetes mellitus (T2DM). The aim of this study was to gain a better insight into the variations in plantar pressure with increased duration of diabetes. METHODS: Plantar pressure was examined in 1196 participants with or without T2DM. Subjects with normal glucose tolerance (NGT) and impaired glucose tolerance (IGT) were assigned to control groups, and those with T2DM were divided into five groups according to diabetes duration (< 2 years, 2-5 years, 5-10 years, 10-15 years, and > 15 years). The clinical characteristics, plantar peak pressure, and pressure-time integral (PTI) were compared among the seven study groups, and factors associated with peak pressure and the PTI were analyzed. RESULTS: At the hallux, peak pressure exhibited an upward trend in patients with T2DM within 5 years of diabetes duration, followed by a distinct downward slope with further progression of the disease (trend analysis, p < 0.05). An uneven distribution of peak pressure was found at other locations, but this unevenness was ultimately lower than that in the two control groups (p < 0.05). No obvious trend was noted for PTI among patients with different diabetes duration; however, those with diabetes for > 10 years manifested a significantly sharper increase in the PTI at the metatarsus (11.63 Ns/cm2, p < 0.05) and heel (14.12 Ns/cm2, p < 0.05) than at the hallux (8.76 Ns/cm2). A fluctuation in the PTI was also detected at the hallux and midfoot of diabetes patients, which was broadly flat when compared with that of the two control groups. The stepwise multiple regression analysis revealed that the variation in plantar pressure was independently associated with age, body mass index, and vibration perception threshold (VPT) (p < 0.05). CONCLUSIONS: There would appear to be an association between longer diabetes duration and decreased peak pressure for the hallux, suggesting that individuals with diabetes for > 10 years will have an increased PTI for the metatarsus and heel. The reduced pressure on the hallux is believed to be transferred to the metatarsus. Age, BMI, and VPT are distinct risk factors of abnormal plantar pressure.

Atherosclerosis in intracranial or extracranial vessels in diabetic patients and the association with stroke subtype.

BACKGROUND: Diabetes mellitus (DM) is associated with increased prevalence and severity of atherosclerosis. This study aimed to assess the prevalence and location of atherosclerosis in intracranial and extracranial vessels in diabetic patients and to investigate their association with ischemic stroke subtype. METHODS: Diabetes patients (n=128) and nondiabetic patients (n=195) were enrolled. Brain MRI, MR angiography, and digital subtraction angiography (DSA) imaging findings in the two groups were retrospectively compared. The characteristics of atherosclerosis (prevalence, location, severity) and collateral flow in diabetic and nondiabetic patients and their association with stroke subtype were analyzed. RESULTS: Atherosclerosis in extracranial vessels was more common in diabetes patients than in nondiabetic patients (43.8% vs. 23.1%; P<0.001). Symptomatic stenoses were commonly in the proximal internal carotid artery (ICA) and proximal vertebral artery (pVA). Diabetes patients were more likely to have lacunar infarction (49.2% vs. 32.3%; P=0.002) and less likely to have large artery infarct (36.7% vs. 48.2%; P=0.042). DM (OR, 2.03; 95% CI, 1.96-4.30; P=0.006) and age >65 years (OR, 2.55; 95% CI, 1.24-5.22; P=0.011) were independent risk factors for lacunar infarct. Diabetes patients with symptomatic extracranial stenosis or occlusion, combined with good collateral circulation, had significantly higher risk of lacunar infarction than nondiabetic patients (47.8% vs. 30.5%; P=0.045). CONCLUSIONS: DM aggravates the severity of extracranial atherosclerosis. Lacunar stroke is relatively common in diabetic patients and could even be due to large artery disease (LAD).

Endothelial progenitor cell-derived exosomes facilitate vascular endothelial cell repair through shuttling miR-21-5p to modulate Thrombospondin-1 expression.

Background: Our previous studies observed that administration of exosomes from endothelial progenitor cells (EPC) facilitated vascular repair in the rat model of balloon injury. However, the molecular events underlying this process remain elusive. Here, we aim to interrogate the key miRNAs within EPC-derived exosomes (EPC-exosomes) responsible for the activation of endothelial cell (EC) repair. Methods: The efficacy of EPC-exosomes in re-endothelialization was examined by Evans Blue dye and histological examination in the rat model of balloon-induced carotid artery injury. The effects of EPC-exosomes on human vascular EC (HUVEC) were also studied by evaluating the effects on growth, migratory and tube formation. To dissect the underlying mechanism, RNA-sequencing assays were performed to determine miRNA abundance in exosomes and mRNA profiles in exosome-treated HUVECs. Meanwhile, in vitro loss of function assays identified an exosomal miRNA and its target gene in EC, which engaged in EPC-exosomes-induced EC repair. Results: Administration of EPC-exosomes potentiated re-endothelialization in the early phase after endothelial damage in the rat carotid artery. The uptake of exogenous EPC-exosomes intensified HUVEC in proliferation rate, migration and tube-forming ability. Integrative analyses of miRNA-mRNA interactions revealed that miR-21-5p was highly enriched in EPC-exosomes and specifically suppressed the expression of an angiogenesis inhibitor Thrombospondin-1 (THBS1) in the recipient EC. The following functional studies demonstrated a fundamental role of miR-21-5p in the pro-angiogenic activities of EPC-exosomes. Conclusions: The present work highlights a critical event for the regulation of EC behavior by EPC-exosomes, which EPC-exosomes may deliver miR-21-5p and inhibit THBS1 expression to promote EC repair.

Comparison of endothelial cell- and endothelial progenitor cell-derived exosomes in promoting vascular endothelial cell repair.

BACKGROUND: Timely endothelial repair after intervention-associated vascular injury is critical to prevent restenosis and thrombosis. Compared to living cell therapies, exosomes may be a better alternative. Thus, we aimed to compare the role of exosomes derived from human umbilical vein endothelial cells (HUVECs) versus those derived from endothelial progenitor cells (EPCs) in vascular endothelial repair. MATERIAL/METHODS: Exosomes secreted from HUVECs and EPCs were isolated and characterized respectively. In vitro, the effects of the two types of exosomes on migration and proliferation of endothelial cells were studied. In vivo, rats were systemically treated with the two exosome groups respectively after carotid artery endothelial injury induced by a balloon. The efficacy in promoting re-endothelialization was measured by Evans blue dye and histological examination. RESULTS: Both types of exosomes, sized from 30 nm to 100 nm, had sphere-shaped or cupped morphology, and expressed CD63, CD9, and CD81; but the total yield of exosomes (particles/mL) based on number of cells, was 4.2 times higher from EPCs than HUVECs. Compared with control treatment, both exosome treated groups manifested significant enhancement of migration and proliferation in vitro and vascular recovery at an early stage in vivo. The two exosome-treated groups, however, did not statistically significantly differ. CONCLUSION: In conclusion, our results indicated that exosomes derived from HUVECs and EPCs had similar morphology, size distributions and characteristics, but those derived from EPCs were more abundant with comparable biologic activity. Therefore, EPCs may be a robust source of exosomes to promote vascular repair.

The value of ankle-branchial index screening for cardiovascular disease in type 2 diabetes.

OBJECTIVE: To investigate the relationship between ankle-branchial index (ABI) and cardiovascular disease in type 2 diabetes patients. METHODS: A total of 634 inpatients with type 2 diabetes were recruited in this cross-sectional study. All patients were measured with ABI and computed tomography angiography (CTA) scan for coronary artery disease (CAD). According to ABI values, patients were divided into three groups: low-ABI group (ABI < 0.9, n = 259), normal-ABI group (ABI = 0.9-1.3, n = 272), and high-ABI group (ABI > 1.3, n = 103). According to the manifestation of coronary CTA, the patients were divided into CAD group (n = 348) and non-CAD group (n = 286). Their clinical data and biochemical parameters were compared and analysed. RESULTS: The prevalence of CAD in low-ABI group (90%) was significantly higher than that of normal-ABI group (33%) and high-ABI group (25%) (both P < 0.01). Spearman correlation analysis showed that age, sex, duration, spontaneous bacterial peritonitis, total cholesterol (TC), triglyceride, low-density lipoprotein cholesterol (LDL-C), serum creatinine, and glycosylated haemoglobin (HbA1c ) were positively correlated with CAD, and high-density lipoprotein cholesterol (HDL-C), glomerular filtration rate, and ABI were negatively correlated with CAD. Logistic regression analysis further revealed that age, sex, duration, TC, HDL-C, LDL-C, HbA1c , and ABI were independent risk factors of CAD. After all potential confounders is adjusted, the risk of CAD in low-ABI group still increased over four times than the normal-ABI group (odds ratio [OR], 5.32; 95% CI, 1.973-16.5; P < 0.001). In female patients, this risk increased more than nine times (OR, 10.63; 95% CI, 3.416-17.8; P < 0.001). Receiver-operating characteristic analysis indicated that ABI < 1.045 predicted the occurrence of CAD (sensitivity, 79.7%; specificity, 71.5%; P < 0.01). CONCLUSIONS: ABI is an independent risk factor for CAD and may be a potential simple screening instrument for CAD in Chinese type 2 diabetic patients, especially in elder women.

Evaluation of Quiescent-Interval Single-Shot Magnetic Resonance Angiography in Diabetic Patients With Critical Limb Ischemia Undergoing Digital Subtraction Angiography: Comparison With Contrast-Enhanced Magnetic Resonance Angiography With Calf Compression at 3.0 Tesla.

PURPOSE: To assess the diagnostic performance of quiescent-interval single-shot magnetic resonance angiography (QISS-MRA) at 3 tesla in diabetic patients with critical limb ischemia (CLI) vs contrast-enhanced MR angiography (CE-MRA) using digital subtraction angiography (DSA) as the standard of reference. METHOD: Thirty-seven consecutive diabetic patients (mean age 71.8±7.2 years; 30 men) with CLI (Fontaine stage III-IV) underwent QISS-MRA and CE-MRA with calf compression; DSA was the standard. Image quality (5-point Likert-type scale) and stenosis severity (5-point grading) for QISS-MRA and CE-MRA were evaluated by 2 blinded readers in 1147 and 654 vessel segments, respectively. Per-segment and per-region (pelvis, thigh, calf) sensitivity, specificity, positive predictive value, and negative predictive value were calculated. RESULTS: Image quality of QISS-MRA was lower compared with CE-MRA in the pelvic region (p<0.001 in both readers) and thigh region (p=0.033 in reader 1 and p=0.018 in reader 2), whereas in the calf region, the image quality of QISS-MRA was better than CE-MRA (p=0.009 in reader 1 and p=0.001 in reader 2). In segment-based analyses, there was no difference between QISS-MRA and CE-MRA in sensitivity [89.5% vs 90.3% in reader 1 (p=0.774) and 87.6% vs 90.6% in reader 2 (p=0.266)] or specificity [94.2% vs 92.9% in reader 1 (p=0.513) and 92.9% vs 92.9% in reader 2 (p>0.999)]. In region-based analyses, QISS-MRA and CE-MRA yielded similar sensitivity and specificity in all areas but the pelvic region for reader 2 (specificity 95.5% vs 84.8%, p=0.041). CONCLUSION: QISS-MRA performed very well in diabetic patients with CLI and was a good alternative for patients with contraindications to CE-MRA.

Integrated application of antegrade and retrograde recanalization for femoral-popliteal artery chronic total occlusions: outcomes compared with antegrade recanalization.

BACKGROUND: To investigate the efficacy of retrograde recanalization for chronic total occlusion (CTO) of femoral-popliteal artery in patients with peripheral arterial disease. METHODS: In this single-center retrospective study, all patients who had undergone endovascular recanalization for femoral-popliteal CTOs at our center from June 2011 to October 2014 were included. Patients' demographics, immediate and follow-up outcomes were analyzed. RESULTS: A total of 205 patients with 238 CTOs were enrolled. In total, successful recanalization was achieved in 228 CTOs (95.8%). The antegrade procedure was successful in 196 CTOs. The retrograde procedure was successfully performed in 32 CTOs after failed antegrade procedure. Ankle-brachial index increased from 0.48±0.18 to 0.79±0.16 in antegrade group vs. 0.41±0.13 to 0.76±0.13 in retrograde group (P=0.438). Pulse score increased from 0.48±0.50 to 2.30±0.76 in antegrade group vs. 0.48±0.51 to 2.30±0.79 in retrograde group (P=0.771). At 12 and 24 months, primary patency rate was 86.2% (169/196) and 51.5% (101/196) in the antegrade group, and 75.0% (24/32) and 43.8% (14/32) in the retrograde group, respectively (P=0.346). Kaplan-Meier analysis showed limb salvage rates of 85.7% in the antegrade group vs. 78.1% in the retrograde group (P=0.198). CONCLUSIONS: Retrograde recanalization is effective for CTO of femoral-popliteal artery after the failure of an antegrade procedure; immediate outcomes and mid-term patency and limb salvage rate are comparable with that of antegrade procedure.