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1.
Mol Med Rep ; 22(1): 474-482, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32377742

RESUMO

Periodontal accelerate osteogenesis orthodontics (PAOO) is an extension of described techniques that surgically alter the alveolar bone; however, the specific mechanism underlying the technique is not completely understood. The aim of the present study was to evaluate the roles of microRNA (miR)­21 during PAOO. Sprague­Dawley rats were divided into the following four groups: i) Group tooth movement (TM), underwent TM and were administered normal saline (NS); ii) Group PAOO, underwent PAOO + TM and were administered NS; iii) Group agomiR­21, underwent PAOO + TM and were administered agomiR­21; and iv) Group antagomiR­21, underwent PAOO + TM and were administered antagomiR­21. To validate the rat model of PAOO, morphological analyses were performed and measurements were collected. Reverse transcription­quantitative PCR, western blotting and immunohistochemical staining were performed to examine the expression levels of programmed cell death 4 (PDCD4), activin A receptor type 2B (ACVR2b), receptor activator of NF­κΒ ligand (RANKL) and C­Fos. Dual­luciferase reporter assays were performed to validate PDCD4 as a target of miR­21 in vitro. Following 7 days of treatment, the TM distance of group PAOO was longer compared with groups TM and antagomiR­21 (P<0.05), but shorter compared with group agomiR­21 (P<0.05). Tartrate­resistant acid phosphatase staining indicated that following treatment with agomiR­21, osteoclast activity was notably increased, whereas the mRNA and protein expression levels of PDCD4 were notably decreased compared with group PAOO. The mRNA and protein expression levels of RANKL and C­Fos in group agomiR­21 were notably increased compared with group PAOO, whereas group antagomiR­21 displayed the opposite pattern (P<0.05). With regard to ACVR2b, no significant differences were observed among the group agomiR­21 and antagomiR­21 compared with group PAOO. Bioinformatics analysis predicted that PDCD4 was a potential target gene of miR­21, and dual­luciferase reporter assays demonstrated that miR­21 directly targeted PDCD4. In conclusion, the present study demonstrated that miR­21 serves an important role during PAOO­mediated orthodontic TM.

2.
Talanta ; 216: 120965, 2020 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-32456924

RESUMO

The development of fluorescent probes for the sensitive and selective determination of highly toxic thiophenols is considerably important in the fields of biological and environmental sciences. Herein, a turn-on fluorescent probe for thiophenol, named MCSH, was constructed based on a pKa shift mechanism, employing merocyanine dye as the fluorophore and 2,-4-dinitrobenzenesulfonamide (DNBS) group as the recognition unit. The imine nitrogen of MCSH has a pKa value of 4.12, which renders its non-fluorescent Schiff base form exclusively under neutral conditions. However, after reacting with thiophenols, its DNBS group was removed to afford a merocyanine dye as the final product, whose pKa value upshifts to 8.11, and was present mainly as the fluorescent protonated Schiff base form under neutral media. Such drastic change in pKa values leads to a significant fluorescence enhancement and can be utilized for the detection of thiophenols. The fluorescence intensity at 627 nm increases linearly with thiophenol concentration in the range of 0.2-3 µM with a detection limit of 15 nM (S/N = 3). MCSH displays high selectivity for the detection of thiophenols over a wide range of other analytes, including aliphatic thiols. Furthermore, the preliminary applications of MCSH for monitoring thiophenols in living cells and environmental have been carried out.

3.
Arterioscler Thromb Vasc Biol ; 40(6): e138-e152, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32459541

RESUMO

In addition to the roles of endothelial cells (ECs) in physiological processes, ECs actively participate in both innate and adaptive immune responses. We previously reported that, in comparison to macrophages, a prototypic innate immune cell type, ECs have many innate immune functions that macrophages carry out, including cytokine secretion, phagocytic function, antigen presentation, pathogen-associated molecular patterns-, and danger-associated molecular patterns-sensing, proinflammatory, immune-enhancing, anti-inflammatory, immunosuppression, migration, heterogeneity, and plasticity. In this highlight, we introduce recent advances published in both ATVB and many other journals: (1) several significant characters classify ECs as novel immune cells not only in infections and allograft transplantation but also in metabolic diseases; (2) several new receptor systems including conditional danger-associated molecular pattern receptors, nonpattern receptors, and homeostasis associated molecular patterns receptors contribute to innate immune functions of ECs; (3) immunometabolism and innate immune memory determine the innate immune functions of ECs; (4) a great induction of the immune checkpoint receptors in ECs during inflammations suggests the immune tolerogenic functions of ECs; and (5) association of immune checkpoint inhibitors with cardiovascular adverse events and cardio-oncology indicates the potential contributions of ECs as innate immune cells.

4.
Nat Commun ; 11(1): 2280, 2020 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-32385245

RESUMO

Renal macrophages (RMs) participate in tissue homeostasis, inflammation and repair. RMs consist of embryo-derived (EMRMs) and bone marrow-derived RMs (BMRMs), but the fate, dynamics, replenishment, functions and metabolic states of these two RM populations remain unclear. Here we investigate and characterize RMs at different ages by conditionally labeling and ablating RMs populations in several transgenic lines. We find that RMs expand and mature in parallel with renal growth after birth, and are mainly derived from fetal liver monocytes before birth, but self-maintain through adulthood with contribution from peripheral monocytes. Moreover, after the RMs niche is emptied, peripheral monocytes rapidly differentiate into BMRMs, with the CX3CR1/CX3CL1 signaling axis being essential for the maintenance and regeneration of both EMRMs and BMRMs. Lastly, we show that EMRMs have a higher capacity for scavenging immune complex, and are more sensitive to immune challenge than BMRMs, with this difference associated with their distinct glycolytic capacities.

5.
Artigo em Inglês | MEDLINE | ID: mdl-32448507

RESUMO

A common, yet often neglectable, feature of neonatal hypoxic-ischemic brain damage (HIBD) is circadian rhythm disorders resulted from pineal gland dysfunction. Our previous work demonstrated that miRNAs play an important role in regulating key circadian genes in the pineal gland post HIBD [5,21]. In current study, we sought out to extend our investigation by profiling expression changes of pineal long non-coding RNAs (lncRNAs) upon neonatal HIBD using RNA-Seq. After validating lncRNA changes, we showed that one lncRNA: TCONS_00044595 is highly enriched in the pineal gland and exhibits a circadian expression pattern. Next, we performed bioinformatic analysis to predict the lncRNA-miRNA regulatory network and identified 168 miRNAs that potentially targetlncRNA TCONS_00044595. We further validated the bona fide interaction between one candidate miRNA: miR-182, a known factor to regulate pineal Clock expression, and lncRNA TCONS_00044595. Finally, we showed that suppression of lncRNA TCONS_00044595 alleviated the CLOCK activation both in the cultured pinealocytes under OGD conditions and in the pineal gland post HIBD in vivo. Our study thus shed light into novel mechanisms of pathophysiology of pineal dysfunction post neonatal HIBD.

6.
BMC Infect Dis ; 20(1): 341, 2020 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-32404057

RESUMO

BACKGROUND: The aim of this study was to evaluate the influence of patient body mass index (BMI) and estimated creatinine clearance (CrCl) on serum vancomycin concentrations to define a possible optimal dosage regimen in overweight patients based on data obtained during therapeutic drug monitoring. METHODS: This retrospective study used data collected from January 2017 to January 2019. Adult patients (n = 204) received vancomycin treatment at a dose of 1000 mg every 12 h and underwent serum monitoring. Data collected included patient disease category, sex, age, height, weight, vancomycin concentrations, and serum creatinine. The CrCl values were estimated using the Cockcroft-Gault formula. In this study, statistical comparisons were performed on the results of patients according to serum vancomycin concentration. RESULTS: Serum vancomycin concentration was significantly related to BMI (P <  0.001) and CrCl (P <  0.05) in adult patients. Furthermore, the trough serum vancomycin concentration showed a logarithmic correlation with BMI (R = - 0.5108, 95% CI: - 0.6082 to - 0.3982, P <  0.001) and CrCl (R = - 0.5739, 95% CI: - 0.6616 to - 0.4707, P <  0.001). The multivariate analysis showed that BMI and CrCl are independent contributors to the trough vancomycin concentration. Moreover, some of the patients with higher BMI (≥ 24 kg/m2) met the goal trough concentration after an adjustment from 1000 mg every 12 h to 1000 mg every 8 h. CONCLUSIONS: Serum vancomycin concentration decreases progressively with increasing BMI and the augmentation in CrCl in adult patients. The trough concentration of vancomycin should be continuously monitored for patients with a BMI ≥ 24 kg/m2, and the dosage regimen should be adjusted to reach the target trough concentration in these patients to reduce the impact of BMI.

7.
Artigo em Inglês | MEDLINE | ID: mdl-32352893

RESUMO

Background: Ventriculostomy-related infection (VRI) is one of the most severe and common complications of external ventricular drains (EVD). Ward environment is closely related to hospital-acquired infection, but its role in EVD infection is unclear. For some other recognized risk factors, clinical evidence also remains complicated and undetermined. We aimed to evaluate ward environment including multi-bed accommodation and intensive care unit (ICU) stay as potential risk factors for VRI, as well as to confirm those already known factors. Methods: We reviewed EVDs retrospectively in our center between January 2012 and January 2017. Univariable and logistic regression analysis were performed to identify risk factors for EVD-related infection. Results: A total of 284 patients who underwent EVD procedure were included. Thirty-six (12.7%) developed EVD-related infection. Univariable analysis revealed that the infection group had longer intensive care unit (ICU) stay (6.81 vs. 3.65 days, p = 0.045) but multi-bed accommodation showed no statistical difference between the two groups (p = 0.404). Univariable analysis also showed VRI patients had lower pre-operational Glasgow Coma Scale (6.89 vs. 9.32, p = 0.001), longer drainage placement duration (11.4 vs. 8.30 days, p < 0.001), greater numbers of cerebrospinal fluid (CSF) sampling (3.89 vs. 1.73, p < 0.001), higher percentage of pre-operational artificial airway status (50.0% vs. 18.1%, p < 0.001), and higher percentage of intracranial hemorrhage diagnosis (88.9% vs. 73.8%, p = 0.048). Logistic regression analysis demonstrated longer post-operational ICU stay (>5 days, odds ratio [OR] = 3.21, p = 0.026) as independent risk factor for EVD-related infection. Other independent risk factors included CSF sampling counts (>3, OR = 5.14, p <0.001), EVD duration (>7 days, OR = 3.85, p = 0.028), and pre-operational artificial airway status (OR = 2.85, p = 0.038). Conclusions: Longer post-operational ICU stay, frequent CSF sampling, longer duration of EVD placement, and pre-operational intubation are independent risk factors for EVD infection. Multi-bed accommodation and bilateral EVD placement have no substantial influence on VRI risk.

8.
Phys Med Biol ; 2020 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-32330922

RESUMO

PURPOSE: Registration and fusion of magnetic resonance imaging (MRI) and transrectal ultrasound (TRUS) of prostate can provide guidance for prostate brachytherapy. However, accurate registration remains a challenging task due to the lack of ground-truth regarding voxel-level spatial correspondence, limited field of view, low contrast-to-noise ratio in TRUS. In this study, we proposed a weakly supervised deep learning approach to address these issues. METHODS: We employed deep learning techniques to combine image segmentation, affine and non-rigid registration to perform a deformable MRI-TRUS registration. First, we trained two separate fully convolutional neural networks to perform MRI and TRUS prostate segmentation. Then, a convolutional neural network was used to rigidly register MRI-TRUS images via affine registration. Third, a UNET-like network was applied for non-rigid registration. For both affine and non-rigid registration. Due to the unavailability of ground truth correspondences and the lack of accurate intensity-based image similarity measures, we propose to use prostate label-derived volume overlaps and surface agreements as an optimization objective function for weakly supervised network training. We proposed a hybrid loss function that integrated Dice and surface-based loss, and a bending energy regularization for the non-rigid registration. RESULTS: 36 sets of patient data were used to test our registration method. Image registration results showed that the deformed MR image aligned well with the TRUS image, as judged by corresponding cysts and calcifications in prostate. Our method produced a mean target registration error (TRE) of 2.53 ±1.39 mm and a mean Dice of 0.91±0.02. The mean surface distance (MSD) and Hausdorff distance (HD) between the registered MR prostate shape and TRUS prostate shape were 0.88 mm and 4.41 mm, respectively. CONCLUSION: This work presents a deep learning-based, weakly supervised network for accurate MRI-TURS image registration. Our proposed method has achieved promising registration performance in terms of Dice, TRE, MSD and HD.

9.
Med Phys ; 2020 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-32323330

RESUMO

BACKGROUND AND PURPOSE: The purpose of this study is to develop a deep learning-based approach to simultaneously segment five pelvic organs including prostate, bladder, rectum, left and right femoral heads on cone-beam CT (CBCT), as required elements for prostate adaptive radiotherapy planning. MATERIALS AND METHODS: We propose to utilize both CBCT and CBCT-based synthetic MRI (sMRI) for the segmentation of soft tissue and bony structures, as they provide complementary information for pelvic organ segmentation. CBCT images have superior bony structure contrast and sMRIs have superior soft tissue contrast. Prior to segmentation, sMRI was generated using a cycle-consistent adversarial networks (CycleGAN), which was trained using paired CBCT-MR images. To combine the advantages of both CBCT and sMRI, we developed a cross-modality attention pyramid network with late feature fusion. Our method processes CBCT and sMRI inputs separately to extract CBCT-specific and sMRI-specific features prior to combining them in a late-fusion network for final segmentation. The network was trained and tested using 100 patients' datasets, with each dataset including the CBCT and manual physician contours. For comparison, we trained another two networks with different network inputs and architectures. The segmentation results were compared to manual contours for evaluations. RESULTS: For the proposed method, dice similarity coefficients and mean surface distances between the segmentation results and the ground truth were 0.96 ± 0.03, 0.65 ± 0.67 mm; 0.91 ± 0.08, 0.93 ± 0.96 mm; 0.93 ± 0.04, 0.72 ± 0.61 mm; 0.95 ± 0.05, 1.05 ± 1.40 mm; and 0.95 ± 0.05, 1.08 ± 1.48 mm for bladder, prostate, rectum, left and right femoral heads, respectively. As compared to the other two competing methods, our method has shown superior performance in terms of the segmentation accuracy. CONCLUSION: We developed a deep learning-based segmentation method to rapidly and accurately segment five pelvic organs simultaneously from daily CBCTs. The proposed method could be used in the clinic to support rapid target and organs-at-risk contouring for prostate adaptive radiation therapy.

10.
BMC Pregnancy Childbirth ; 20(1): 190, 2020 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-32228498

RESUMO

BACKGROUND: Blood flow in the corpus luteum is associated with luteal function. However, the impact of luteal blood flow on methotrexate (MTX) treatment in women with unruptured tubal pregnancy has not been reported. The aim of the present study was to observe the impact of luteal blood flow on the therapeutic effect of MTX in women with unruptured tubal pregnancy. METHODS: A prospective observational study recruited 129 women with unruptured tubal pregnancy in the First Affiliated Hospital of Xi'an Jiaotong University from September 2016 to June 2018. One hundred and fifteen women were treated successfully with MTX, and women were divided into 2 groups according to luteal blood flow: the poor luteal blood flow group and the abundant luteal blood flow group. The therapeutic effects were compared between the two groups. RESULTS: Women in the abundant luteal blood flow group had a significantly higher serum ß-human chorionic gonadotropin (ß-hCG) level 4 days, 1 week and 2 weeks after MTX treatment compared with women in the poor luteal blood flow group (P < 0.05). The average diameter of the ectopic mass 1 week, 2 weeks and 3 weeks after MTX treatment in women with abundant luteal blood flow was significantly larger (P < 0.05), and the time of serum ß-hCG clearance and ectopic mass disappearance were significantly longer compared with those in women in the poor luteal blood flow group (P < 0.05). CONCLUSIONS: Luteal blood flow might be a predictive factor for MTX treatment outcomes in women with unruptured tubal pregnancy, and those with abundant luteal blood flow need a longer recovery time.

11.
Artigo em Inglês | MEDLINE | ID: mdl-32296394

RESUMO

Background: Polycystic ovary syndrome (PCOS) is a common endocrine disorder in women at reproductive age, which is characterized by obesity, hyperandrogenemia, and insulin resistance (IR). This study aimed to investigate the vitamin D status, and analyze the relationship between vitamin D deficiency and metabolic risk factors in PCOS women in Shaanxi China. Methods: A cross-sectional study included 169 women diagnosed with PCOS and 114 control women without PCOS. The serum 25(OH)D and metabolic markers were measured. Vitamin D deficiency was defined as serum 25(OH)D concentration less than 20 ng/mL. The primary outcome was the difference in vitamin D status between the PCOS and control groups, the secondary outcomes were correlations between serum 25(OH)D concentration and metabolic risk factors in women with PCOS. Results: The serum 25(OH)D concentration was significantly lower in women with PCOS than in controls (P < 0.05), and the prevalence rates of 25(OH)D deficiency and insufficiency were significantly higher in women with PCOS than in controls (P < 0.05). The serum 25(OH)D concentration was significantly lower in PCOS women with obesity or IR than in women without obesity or IR (P < 0.05), and the prevalence of 25(OH)D deficiency in PCOS women with obesity or IR was significantly higher than in women without obesity or IR (P < 0.05). Serum 25(OH)D concentration was significantly negatively correlated with body mass index (BMI), waist-to-hip ratio (WHR), fasting insulin, homeostasis model assessment of insulin resistance (HOMA-IR), total cholesterol, low-density lipoprotein cholesterol (LDL-C), and high-sensitivity C-reactive protein (hs-CRP) (P < 0.05). In comparison, serum 25(OH)D concentration was significantly positively correlated with high-density lipoprotein cholesterol (HDL-C) (P < 0.05). Increased BMI and WHR, high levels of fasting insulin, HOMA-IR, total cholesterol, LDL-C and hs-CRP were regarded as risk factors, but high level of HDL-C was considered to be protective factor of vitamin D deficiency in PCOS women. Conclusions: Vitamin D deficiency is prevalent in PCOS women in Shaanxi China, especially in those with obesity and IR. The serum 25(OH)D level was correlated with metabolic risk factors in PCOS women. Multi-center randomized controlled trials with large sample sizes are needed to probe the metabolic effect of vitamin D supplementation in PCOS women.

12.
J Integr Neurosci ; 19(1): 31-37, 2020 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-32259884

RESUMO

Post-traumatic hydrocephalus is a common complication secondary to traumatic brain injury. It can cause cerebral metabolic impairment and dysfunction. Therefore, timely treatment with shunt implantation is necessary. However, the outcomes of shunt surgery in patients with post-traumatic hydrocephalus combined with disturbance of consciousness are doubtful. The objective was to develop a predictive model that uses the information available before surgery to predict the outcome of shunt implantation in such patients. Retrospectively collected data were used to develop a clinical prediction model. The model was derived from 59 patients using logistic regression analysis, and then it was evaluated by the area under the receiver operating characteristic curve and Hosmer-Lemshow test. A validation cohort verified the model. Four independent predictors were identified: age < 50 years, mild hydrocephalus, Glasgow Coma Scale scores 9-12 at the time of injury, and time interval from trauma to shunting < 3 months. We calculated the total score and defined the patients into three groups: low-probability (0-10 points), medium-probability (11-16 points), and high-probability (17-30 points). The rates of improved outcomes in the three groups were 14.3%, 52.6%, and 94.7%, respectively (P < 0.0001). The correlative rates of the validation cohort were 21.4%, 54.5%, and 85.7%. The prognostic model showed good discrimination (area under the receiver operating characteristic curve = 0.869) and calibration (Hosmer-Lemshow test, P = 0.391). The developed predictive model can identify patients with post-traumatic hydrocephalus combined with disturbance of consciousness who can benefit from shunt implantation. Therefore, our prognostic model can predict the outcomes of patients with post-traumatic hydrocephalus and disturbance of consciousness after shunt surgery.

13.
Phys Med Biol ; 65(9): 095012, 2020 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-32182595

RESUMO

Epicardial adipose tissue (EAT) is a visceral fat deposit, that's known for its association with factors, such as obesity, diabetes mellitus, age, and hypertension. Segmentation of the EAT in a fast and reproducible way is important for the interpretation of its role as an independent risk marker intricate. However, EAT has a variable distribution, and various diseases may affect the volume of the EAT, which can increase the complexity of the already time-consuming manual segmentation work. We propose a 3D deep attention U-Net method to automatically segment the EAT from coronary computed tomography angiography (CCTA). Five-fold cross-validation and hold-out experiments were used to evaluate the proposed method through a retrospective investigation of 200 patients. The automatically segmented EAT volume was compared with physician-approved clinical contours. Quantitative metrics used were the Dice similarity coefficient (DSC), sensitivity, specificity, Jaccard index (JAC), Hausdorff distance (HD), mean surface distance (MSD), residual mean square distance (RMSD), and the center of mass distance (CMD). For cross-validation, the median DSC, sensitivity, and specificity were 92.7%, 91.1%, and 95.1%, respectively, with JAC, HD, CMD, MSD, and RMSD are 82.9% ± 8.8%, 3.77 ± 1.86 mm, 1.98 ± 1.50 mm, 0.37 ± 0.24 mm, and 0.65 ± 0.37 mm, respectively. For the hold-out test, the accuracy of the proposed method remained high. We developed a novel deep learning-based approach for the automated segmentation of the EAT on CCTA images. We demonstrated the high accuracy of the proposed learning-based segmentation method through comparison with ground truth contour of 200 clinical patient cases using 8 quantitative metrics, Pearson correlation, and Bland-Altman analysis. Our automatic EAT segmentation results show the potential of the proposed method to be used in computer-aided diagnosis of coronary artery diseases (CADs) in clinical settings.

14.
World J Urol ; 2020 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-32130476

RESUMO

BACKGROUND: To evaluate the surgical safety of en bloc resection of bladder tumor (ERBT) and the effectiveness of ERBT combined with near-infrared (NIR) imaging technique in the diagnosis and treatment of non-muscle invasive bladder cancer (NMIBC). METHODS: From October 2017 to June 2018, 26 patients newly diagnosed with single NMIBC were included in this retrospectively trial. All patients received ERBT with monopolar current. After surgery, the fresh specimen was incubated with anti-CD47-Alexa Fluor 790, and then imaged under NIR imaging technique. Operative details, intraoperative and postoperative complications of ERBT regarded as safety outcomes, the mean fluorescence intensity (MFI) of tumor tissue and adjacent normal background tissue, and 12 months follow-up data were analyzed. RESULTS: Of 26 collected patients, obturator nerve reflex was occurred in six patients during tumor resection, and only one patient was observed with bladder perforation. In NIR gray image, the gray scale of MFI of tumor tissue were 132.31 ± 6.67 and the adjacent normal background tissue were 52.27 ± 12.09. The result showed a significantly higher MFI signals in tumor tissue compared to adjacent normal background tissue (P < 0.001). The recurrence-free survival rate at 12 month was 96.15%. CONCLUSIONS: ERBT with monopolar current is a safe and feasible technique to treat patients with NMIBC. A integrated bladder tumor tissue-bound anti-CD47-Alexa Fluor 790 was detected under NIR light, and the NIR image indicates that higher MFI signals in surgical margin is a predictive factor for residual tumor in patients with NMIBC after ERBT.

15.
Redox Biol ; : 101460, 2020 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-32179051

RESUMO

BACKGROUND: The molecular mechanisms underlying chronic kidney disease (CKD) transition to end-stage renal disease (ESRD) and CKD acceleration of cardiovascular and other tissue inflammations remain poorly determined. METHODS: We conducted a comprehensive data analyses on 7 microarray datasets in peripheral blood mononuclear cells (PBMCs) from patients with CKD and ESRD from NCBI-GEO databases, where we examined the expressions of 2641 secretome genes (SG). RESULTS: 1) 86.7% middle class (molecular weight >500 Daltons) uremic toxins (UTs) were encoded by SGs; 2) Upregulation of SGs in PBMCs in patients with ESRD (121 SGs) were significantly higher than that of CKD (44 SGs); 3) Transcriptomic analyses of PBMC secretome had advantages to identify more comprehensive secretome than conventional secretomic analyses; 4) ESRD-induced SGs had strong proinflammatory pathways; 5) Proinflammatory cytokines-based UTs such as IL-1ß and IL-18 promoted ESRD modulation of SGs; 6) ESRD-upregulated co-stimulation receptors CD48 and CD58 increased secretomic upregulation in the PBMCs, which were magnified enormously in tissues; 7) M1-, and M2-macrophage polarization signals contributed to ESRD- and CKD-upregulated SGs; 8) ESRD- and CKD-upregulated SGs contained senescence-promoting regulators by upregulating proinflammatory IGFBP7 and downregulating anti-inflammatory TGF-ß1 and telomere stabilizer SERPINE1/PAI-1; 9) ROS pathways played bigger roles in mediating ESRD-upregulated SGs (11.6%) than that in CKD-upregulated SGs (6.8%), and half of ESRD-upregulated SGs were ROS-independent. CONCLUSIONS: Our analysis suggests novel secretomic upregulation in PBMCs of patients with CKD and ESRD, act synergistically with uremic toxins, to promote inflammation and potential disease progression. Our findings have provided novel insights on PBMC secretome upregulation to promote disease progression and may lead to the identification of new therapeutic targets for novel regimens for CKD, ESRD and their accelerated cardiovascular disease, other inflammations and cancers. (Total words: 279).

16.
Med Phys ; 2020 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-32155666

RESUMO

PURPOSE: Ultrasound (US)-guided high dose rate (HDR) prostate brachytherapy requests the clinicians to place HDR needles (catheters) into the prostate gland under transrectal US (TRUS) guidance in the operating room. The quality of the subsequent radiation treatment plan is largely dictated by the needle placements, which varies upon the experience level of the clinicians and the procedure protocols. Real-time plan dose distribution, if available, could be a vital tool to provide more subjective assessment of the needle placements, hence potentially improving the radiation plan quality and the treatment outcome. However, due to low signal-to-noise ratio (SNR) in US imaging, real-time multi-needle segmentation in 3D TRUS, which is the major obstacle for real-time dose mapping, has not been realized to date. In this study, we propose a deep learning-based method that enables accurate and real-time digitization of the multiple needles in the 3D TRUS images of HDR prostate brachytherapy. METHODS: A deep learning model based on the U-Net architecture was developed to segment multiple needles in the 3D TRUS images. Attention gates were considered in our model to improve the prediction on the small needle points. Furthermore, the spatial continuity of needles was encoded into our model with total variation (TV) regularization. The combined network was trained on 3D TRUS patches with the deep supervision strategy, where the binary needle annotation images were provided as ground truth. The trained network was then used to localize and segment the HDR needles for a new patient's TRUS images. We evaluated our proposed method based on the needle shaft and tip errors against manually defined ground truth and compared our method with other state-of-art methods (U-Net and deeply supervised attention U-Net). RESULTS: Our method detected 96% needles of 339 needles from 23 HDR prostate brachytherapy patients with 0.290 ± 0.236 mm at shaft error and 0.442 ± 0.831 mm at tip error. For shaft localization, our method resulted in 96% localizations with less than 0.8 mm error (needle diameter is 1.67 mm), while for tip localization, our method resulted in 75% needles with 0 mm error and 21% needles with 2 mm error (TRUS image slice thickness is 2 mm). No significant difference is observed (P = 0.83) on tip localization between our results with the ground truth. Compared with U-Net and deeply supervised attention U-Net, the proposed method delivers a significant improvement on both shaft error and tip error (P < 0.05). CONCLUSIONS: We proposed a new segmentation method to precisely localize the tips and shafts of multiple needles in 3D TRUS images of HDR prostate brachytherapy. The 3D rendering of the needles could help clinicians to evaluate the needle placements. It paves the way for the development of real-time plan dose assessment tools that can further elevate the quality and outcome of HDR prostate brachytherapy.

17.
Phys Med Biol ; 2020 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-32217829

RESUMO

This paper presents a review of deep learning (DL) based medical image registration methods. We summarized the latest developments and applications of DL-based registration methods in the medical field. These methods were classified into seven categories according to their methods, functions and popularity. A detailed review of each category was presented, highlighting important contributions and identifying specific challenges. A short assessment was presented following the detailed review of each category to summarize its achievements and future potentials. We provided a comprehensive comparison among DL-based methods for lung and brain registration using benchmark datasets. Lastly, we analyzed the statistics of all the cited works from various aspects, revealing the popularity and future trend of DL-based medical image registration.

18.
Med Phys ; 2020 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-32141618

RESUMO

PURPOSE: Current clinical application of cone-beam CT (CBCT) is limited to patient setup. Imaging artifacts and Hounsfield unit (HU) inaccuracy make the process of CBCT-based adaptive planning presently impractical. In this study, we developed a deep-learning-based approach to improve CBCT image quality and HU accuracy for potential extended clinical use in CBCT-guided pancreatic adaptive radiotherapy. METHODS: Thirty patients previously treated with pancreas SBRT were included. The CBCT acquired prior to the first fraction of treatment was registered to the planning CT for training and generation of synthetic CT (sCT). A self-attention cycle generative adversarial network (cycleGAN) was used to generate CBCT-based sCT. For the cohort of 30 patients, the CT-based contours and treatment plans were transferred to the first fraction CBCTs and sCTs for dosimetric comparison. RESULTS: At the site of abdomen, mean absolute error (MAE) between CT and sCT was 56.89 ± 13.84 HU, comparing to 81.06 ± 15.86 HU between CT and the raw CBCT. No significant differences (P > 0.05) were observed in the PTV and OAR dose-volume-histogram (DVH) metrics between the CT- and sCT-based plans, while significant differences (P < 0.05) were found between the CT- and the CBCT-based plans. CONCLUSIONS: The image similarity and dosimetric agreement between the CT and sCT-based plans validated the dose calculation accuracy carried by sCT. The CBCT-based sCT approach can potentially increase treatment precision and thus minimize gastrointestinal toxicity.

19.
Anal Chem ; 92(8): 5733-5740, 2020 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-32193934

RESUMO

Small-molecular fluorescence sensors have become promising detection tools in many fields attributing to their high sensitivity, excellent temporal and spatial resolution, and low cytotoxicity. However, high concentration or aggregation-induced fluorescence quenching effect has usually hindered the development of traditional fluorescence dyes. Herein, a new fluorophore cyanovinylene dye BMZ with excimer emission property has been constructed. It shows an obvious enhanced and red-shift emission upon aggregation in aqueous solution, which overmatches the conventional pyrene with longer absorption and emission wavelengths. Using this unique optical property, a new fluorescence probe BMZ-Gal has been developed for trapping of ß-galactosidase (ß-Gal) activity with high selectivity, low limit of detection of 0.17 U, and rapid recognition, which is based on the ß-Gal-induced formation of red-shift emitting excimer. ß-Gal has a strong affinity for BMZ-Gal, which is verified through the Michaelis-Menten constants (Km, 1.87 µM) and the hydrolysis efficiencies (Kcat/Km, 1.78 × 103 M-1 s-1). Furthermore, the assay system has been successfully used for detecting endogenous ß-Gal in living ovarian cancer cells and can passively targeted to identify ß-Gal in organelle level and determine its subcellular location with satisfactory accuracy. We anticipate that the new fluorophore cyanovinylene dye herein may inaugurate new opportunities for the development of excimer emission sensors.

20.
Front Immunol ; 11: 284, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32153588

RESUMO

Atherosclerosis, a chronic inflammatory disease of the arterial wall, is among the leading causes of morbidity and mortality worldwide. The persistence of low-grade vascular inflammation has been considered to fuel the development of atherosclerosis. However, fundamental mechanistic understanding of the establishment of non-resolving low-grade inflammation is lacking, and a large number of atherosclerosis-related cardiovascular complications cannot be prevented by current therapeutic regimens. Trained immunity is an emerging new concept describing a prolonged hyperactivation of the innate immune system after exposure to certain stimuli, leading to an augmented immune response to a secondary stimulus. While it exerts beneficial effects for host defense against invading pathogens, uncontrolled persistent innate immune activation causes chronic inflammatory diseases. In light of the above, the long-term over-activation of the innate immune system conferred by trained immunity has been recently hypothesized to serve as a link between non-resolving vascular inflammation and atherosclerosis. Here, we provide an overview of current knowledge on trained immunity triggered by various exogenous and endogenous inducers, with particular emphasis on its pro-atherogenic effects and the underlying intracellular mechanisms that act at both the cellular level and systems level. We also discuss how trained immunity could be mechanistically linked to atherosclerosis from both preclinical and clinical perspectives. This review details the mechanisms underlying the induction of trained immunity by different stimuli, and highlights that the intracellular training programs can be different, though partly overlapping, depending on the stimulus and the biological system. Thus, clinical investigation of risk factor specific innate immune memory is necessary for future use of trained immunity-based therapy in atherosclerosis.

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