Detection of Endoleak after Endovascular Aortic Repair through Deep Learning Based on Non-contrast CT.

OBJECTIVES: To develop and validate a deep learning model for detecting post-endovascular aortic repair (EVAR) endoleak from non-contrast CT. METHODS: This retrospective study involved 245 patients who underwent EVAR between September 2016 and December 2022. All patients underwent both non-enhanced and enhanced follow-up CT. The presence of endoleak was evaluated based on computed tomography angiography (CTA) and radiology reports. First, the aneurysm sac was segmented, and radiomic features were extracted on non-contrast CT. Statistical analysis was conducted to investigate differences in shape and density characteristics between aneurysm sacs with and without endoleak. Subsequently, a deep learning model was trained to generate predicted segmentation of the endoleak. A binary decision was made based on whether the model produced a segmentation to detect the presence of endoleak. The absence of a predicted segmentation indicated no endoleak, while the presence of a predicted segmentation indicated endoleak. Finally, the performance of the model was evaluated by comparing the predicted segmentation with the reference segmentation obtained from CTA. Model performance was assessed using metrics such as dice similarity coefficient, sensitivity, specificity, and the area under the curve (AUC). RESULTS: This study finally included 85 patients with endoleak and 82 patients without endoleak. Compared to patients without endoleak, patients with endoleak had higher CT values and greater dispersion. The AUC in validation group was 0.951, dice similarity coefficient was 0.814, sensitivity was 0.877, and specificity was 0.884. CONCLUSION: This deep learning model based on non-contrast CT can detect endoleak after EVAR with high sensitivity.

Revealing PPP1R12B and COL1A1 as piRNA pathway genes contributing to abdominal aortic aneurysm through integrated analysis and experimental validation.

BACKGROUND: Abdominal aortic aneurysm (AAA) is a permanent dilation of the abdominal aorta, with a high mortality rate when rupturing. Although lots of piRNA pathway genes (piRPGs) have recently been linked to both neoplastic and non-neoplastic illnesses, their role in AAA is still unknown. Utilizing integrative bioinformatics methods, this research discovered piRPGs as biomarkers for AAA and explore possible molecular mechanisms. METHODS: The datasets were obtained from the Gene Expression Omnibus and piRPGs were identified from the Genecards database. The "limma" and "clusterProfiler" R-packages were used to discover differentially expressed genes and perform enrichment analysis, respectively. Hub piRPGs were further filtered using least absolute shrinkage and selection operator regression, random forests, as well as receiver operating characteristic curve. Additionally, multi-factor logistic regression (MLR), extreme gradient boosting (XGboost), and artificial neural network (ANN) were employed to construct prediction models. The relationship between hub piRPGs and immune infiltrating cells and sgGSEA were further studied. The expression of hub piRPGs was verified by qRT-PCR, immunohistochemistry, and western blotting in AAA and normal vascular tissues and analyzed by scRNA-seq in mouse AAA model. SRAMP and cMAP database were utilized for the prediction of N6-methyladenosine (m6A) targets therapeutic drug. RESULTS: 34 differentially expressed piRPGs were identified in AAA and enriched in pathways of immune regulation and gene silence. Three piRPGs (PPP1R12B, LRP10, and COL1A1) were further screened as diagnostic genes and used to construct prediction model. Compared with MLR and ANN, Xgboost showed better predictive ability, and PPP1R12B might have the ability to distinguish small and large AAA. Furthermore, the expression levels of PPP1R12B and COL1A1 were consistent with the results of bioinformatics analysis, and PPP1R12B showed a downward trend that may be related to m6A. CONCLUSION: The results suggest that piRPGs might serve a significant role in AAA. PPP1R12B, COL1A1, and LRP10 had potential as diagnostic-specific biomarkers for AAA and performed better in XGboost model. The expression and localization of PPP1R12B and COL1A1 were experimentally verified. Besides, downregulation of PPP1R12B caused by m6A might contribute to the formation of AAA.

A Comparison of Clinical Characteristics in Overweight/Obese and Normal Weight Patients with Psoriasis Vulgaris: A Bicentric Retrospective Observational Study.

Background: Psoriasis is a chronic, inflammatory skin disease that is often accompanied by multiple comorbidities. Obesity is considered an independent risk factor for the development of psoriasis. However, most of the related data are derived from epidemiological studies conducted in the United States of America and Europe. This study aimed to compare the clinical characteristics of patients with psoriasis who are overweight/obese and patients with psoriasis with normal weight in China. Methods: We reviewed the medical records of 208 patients with psoriasis. Based on their body mass index (BMI), the patients were divided into two groups: patients with psoriasis who were overweight/obese and patients with psoriasis with normal weight. Results: The most patients enrolled in this study were men (77.40%). Patients with psoriasis who were overweight/obese had a higher mean age, longer disease duration, and significantly higher Psoriasis Area and Severity Index (PASI) values (P=0.032). Additionally, the incidence of fatty liver, hyperlipidemia, hyperuricemia, and abnormal liver function was higher among patients with psoriasis who were overweight/obese (P<0.05). Linear regression analysis revealed a linear relationship between PASI values and BMI (P=0.016). Moreover, patients with psoriasis who were overweight/obese had significantly higher levels of serum alanine transaminase (ALT), aspartate transaminase (AST), uric acid (UC), total cholesterol (TC), low-density lipoprotein (LDL), and fasting plasma glucose (FPG) (P<0.05) and lower serum high-density lipoprotein (HDL) levels and absolute lymphocyte count (ALC) (P<0.05). Conclusion: Patients with psoriasis who are overweight/obese have more severe psoriatic lesions and metabolic comorbidities. Detailed assessment of the BMI of patients with psoriasis revealed that weight loss may be necessary for patients who are overweight/obese to reduce the risk of metabolic disorders.

The fabrication and evaluation of silver nanoparticle-based keratin scaffolds.

The biotoxicity caused by focus releasing of Ag, which associated with the Ag loading mode, is a problematic issue that need to be solved for practical utilization of the keratin based wound dressing. In this study, keratin/AgNPs blend scaffolds (Ker/Ag) and keratin scaffolds with AgNPs attached on the scaffold's wall surface (Ag@Ker) were prepared. Structure and physical properties of the scaffolds were tested and investigated. In comparison to the Ag@Ker scaffolds, the Ker/Ag scaffolds with uniform dispersion of AgNPs have larger tensile strength and slower degradation rate. Both kind of scaffolds present excellent antibacterial property with 10 µg mL-1 AgNPs addition, while the Ker/Ag displayed a linear Ag releasing ratio in the first 5-7 days, which is beneficial for obtaining a continuous antibacterial property and avoiding the biotoxicity caused by focus release of Ag. Correspondingly, cytotoxicity assay further reveals that the continuously slow release of Ag of the Ker/Ag scaffolds accelerated the proliferation of cell. Infectious animal models and histological studies showed that the Ker/Ag scaffolds can effectively inhibit the inflammatory response and accelerate epithelialization. Thus, it can be concluded that the Ker/Ag scaffolds with uniform dispersion of AgNPs are more attractive as wound repair materials.

Art Therapy Alleviates the Levels of Depression and Blood Glucose in Diabetic Patients: A Systematic Review and Meta-Analysis.

Objective: To systematically analyze the effects of art therapy on the levels of depression, anxiety, blood glucose, and glycated hemoglobin in diabetic patients. Methods: We searched Cochrane Library, PubMed, Embase, and ClinicalTrials.gov databases from inception to January 24, 2021. The language of publication was limited to English. Randomized controlled trials (RCTs) that used art therapy to improve mental disorders in diabetic patients were involved. After selection of eligible studies, data were extracted, including the first author's full-name, year of publication, the first author's country of residence, number of intervention and control groups, the mean age of participants, method of intervention, duration of follow-up, and outcome measures. Assessment of quality of the included studies and data extraction were independently carried out by two researchers. RevMan 5.3 software was used to perform statistical analysis. Results: A total of 396 samples from five studies were included, and the eligible studies were RCTs with a parallel design. Methods of art therapy included music therapy and painting therapy. The results showed that compared with the control group, art therapy could positively affect the levels of depression [standardized mean difference (SMD), -1.36; 95% confidence interval (CI), (-1.63, -1.09); P < 0.00001] and blood glucose in diabetic patients [mean difference (MD), -0.90; 95% CI, (-1.03, -0.77); P < 0.0001], while it had no influence on the levels of anxiety [SMD, -0.31; 95% CI, (-0.93, 0.31); P = 0.32] and glycated hemoglobin [MD, 0.22; 95% CI, (-0.02, 0.46); P = 0.07]. Conclusion: Art therapy may have significant effects on the levels of depression and blood glucose for diabetic patients.

Photodynamic therapy in the treatment of xeroderma pigmentosum: A case report.

Xeroderma pigmentosum (XP) is a rare autosomal recessive dermatosis that is often complicated by multiple skin tumours at exposed locations, which are difficult to treat. We report a case of a 12-year-old girl with XP treated with oral retinoic acid and photodynamic therapy (PDT) with good clinical results. She had an 8-year history of multiple skin lesions that first appeared on her nasal dorsum, but gradually increased in size and spread to her entire face, neck, and upper limbs. Notably, the lesions became evidently aggravated after sun exposure. When she was 6 years old, sesame-seed-sized papules and plaques appeared, which were fragile and irregular in shape and would self-rupture, accompanied with slight itchiness and bloody exudate. Examination revealed multiple basal cell carcinomas. The tumours were treated with local carbon dioxide laser therapy combined with PDT. On the follow-up visit 2 months after the surgery, most of the skin lesions on her face had subsided. In cases of multiple tumours, PDT can be the treatment method of choice because it is less invasive, has less side effects, and does not damage the surrounding normal tissues.

Hydroxychloroquine protects melanocytes from autoantibody-induced injury by reducing the binding of antigen-antibody complexes.

Vitiligo is a polygenic autoimmune disorder characterized by loss of pigmentation due to melanocyte destruction. Hydroxychloroquine (HCQ) is an effective immunosuppressant widely used in the treatment of autoimmune disorders. As generalized vitiligo (GV) is commonly considered to be a T cell and autoantibody-induced immune disorder, the present study aimed to determine whether HCQ protects melanocytes from autoantibody­induced disruption. Anti­melanocyte antibodies were obtained from the serum of patients with progressive GV and the effects of HCQ on prevent the autoantibody­induced disruption of melanocytes was observed. Cell­based ELISA, indirect immunofluorescence and western blotting were used to analyze the autoantibody content of sera samples obtained from 32 patients with progressive GV. The cytotoxicity of HCQ was detected by MTT assay, and 1 µg/ml HCQ was applied to human primary melanocytes (HMCs) to examine whether it could exert protective effects against autoantibody­induced immune injury. Flow cytometry was used to measure autoantibody binding to the surface of HMCs. Complement­dependent cytotoxicity (CDC) and antibody­dependent cell­mediated cytotoxicity (ADCC) were monitored by MTT and lactate dehydrogenase­releasing assays. The concentration of autoantibodies in sera samples taken from GV patients was significantly higher than in controls, particularly in patients who had >10% of their body surface affected by vitiligo. The majority of the autoantibodies presented in the HMCs and human keratinocytes (HKCs) and were predominantly localized to the cell surface and cytoplasm. The molecular weights of the autoantigens were identified as 30, 37­39, 42, 53, 60­75, 90, 100, 110, and 126 kDa; the 30 kDa protein was observed only in HMCs. The addition of HCQ at a concentration of 1 µg/ml produced no significant cytotoxicity in HMCs and was demonstrated to reduce the binding of GV immunoglobulin G (IgG) to the surface of HMCs. HCQ also significantly decreased the effects of ADCC and CDC that were mediated by GV IgG. The present study provides evidence that HCQ dissociates autoantibody-antigen complexes on the surface of HMCs and reverses ADCC and CDC activity in vitro. Thus, in addition to its effectiveness as an antimalarial therapeutic agent, HCQ may also be a promising potential treatment for patients with vitiligo.

Efficacy and safety of fluocinolone acetonide, hydroquinone, and tretinoin cream in chinese patients with melasma: a randomized, double-blind, placebo-controlled, multicenter, parallel-group study.

BACKGROUND AND OBJECTIVES: This study aimed to determine the efficacy and safety of fluocinolone acetonide, hydroquinone, and tretinoin (FAHT) cream for the treatment of moderate and severe facial melasma. The primary objective was assessment of clinical efficacy, instrumental measured efficacy, and integral therapeutic efficacy at the end of weeks 4 and 8. METHODS: A total of 233 subjects were randomly allocated (1:1 ratio) to receive topically administered FAHT cream (n = 117) or placebo (n = 116) once nightly for 8 weeks. Observed side effects were documented throughout. RESULTS: In the per protocol set (PPS; those subjects who met all requirements of the protocol), the integral therapeutic efficacy rate of FAHT cream on moderate and severe melasma was 68.57% (vs. placebo, 0.94%), the clinical effective rate of FAHT cream was 74.29 % (vs. placebo, 0.94%), and the instrumental measure efficacy of FAHT cream was 71.43% (vs. placebo, 6.60%). The difference in efficacy between the two groups was statistically significant (p < 0.001). In the full analysis set (FAS; the PPS and those subjects who were lost to follow-up but received at least one study treatment), the integral therapeutic efficacy rate of FAHT cream was 64.60% (vs. placebo, 0.88%), the clinical effective rate of FAHT cream was 69.91% (vs. placebo, 0.88%), and the instrumental measure efficacy of FAHT cream was 69.03 % (vs. placebo, 7.08%). The difference in efficacy between the two groups was statistically significant (p < 0.001). Of 113 subjects in the FAHT group, 34 (30.1%) reported adverse effects. Most of the pathological adverse effects were mild and resolved with either continuous treatment or discontinuation. Of 113 subjects in the placebo group, three (2.6%) reported mild adverse effects. No severe adverse effects or other abnormal clinical results were associated with the study treatment. CONCLUSION: FAHT cream is efficacious, well tolerated, and has a high margin of safety for the treatment of moderate and severe melasma in the Chinese population.

MITF-siRNA formulation is a safe and effective therapy for human melasma.

It is unclear whether siRNA-based agents can be a safe and effective therapy for diseases. In this study, we demonstrate that microphthalmia-associated transcription factor-siRNA (MITF-siR)-silenced MITF gene expression effectively induced a significant reduction in tyrosinase (TYR), tyrosinase-related protein 1, and melanocortin 1 receptor (MC1R) levels. The siRNAs caused obvious inhibition of melanin synthesis and melanoma cell apoptosis. Using a novel type of transdermal peptide, we developed the formulation of an MITF-siR cream. Results demonstrated that hyperpigmented facial lesions of siRNA-treated subjects were significantly lighter after 12 weeks of therapy than before treatment (P < 0.001); overall improvement was first noted after 4 weeks of siRNA treatment. At the end of treatment, clinical and colorimetric evaluations demonstrated a 90.4% lightening of the siRNA-treated lesions toward normal skin color. The relative melanin contents in the lesions and adjacent normal skin were decreased by 26% and 7.4%, respectively, after treatment with the MITF-siR formulation. Topical application of siRNA formulation significantly lightens brown facial hypermelanosis and lightens normal skin in Asian individuals. This treatment represents a safe and effective therapy for melasma, suggesting that siRNA-based agents could be developed for treating other diseases such as melanoma.

Efficacy of quantifying melanosome transfer with flow cytometry in a human melanocyte-HaCaT keratinocyte co-culture system in vitro.

In this study, we describe a simple, specific, reproducible and quantitative assay system to assess melanosome transfer. We first established a co-culture model of normal human epidermal melanocytes and HaCaT keratinocytes. The cells were co-cultured for 72 h in a serum-free keratinocyte growth media and double labelled with Fluorescein isothiocyanate (FITC)-conjugated antibody against the melanosome-specific protein gp100, and with Phycoerythrin (PE)-conjugated antibody against the keratinocyte-specific marker cytokeratin. Then, the cells were examined using co-focal microscope and flow cytometry. The increased melanosome transfer from melanocytes to HaCaT keratinocytes was observed in a time-dependent manner. To verify the accessibility of this method, two known melanosome transfer inhibitors and two known melanosome transfer stimulators were applied. Consistent with previous investigation, soybean trypsin inhibitor (STI), niacinamide inhibited melanosome transfer, alpha-melanocyte stimulating hormone (alpha-MSH) and keratinocyte growth factor (KGF) increased melanosome transfer, respectively, in a dose-dependent manner. The model used in this study could thus represent a rapid and reliable tool to identify modulators of human melanosome transfer.

Oligomeric proanthocyanidins from grape seeds effectively inhibit ultraviolet-induced melanogenesis of human melanocytes in vitro.

The oligomeric proanthocyanidins (OPCs) from grape seeds are expected to be novel and potent anti-oxidants that more effectively protect skin cells against oxidative stress. UV-induced oxidative stress is considered to promote melanogenesis and serious skin damage. However, the effect of OPCs on UV-induced melanogenesis is still unknown. To investigate the role of OPCs on melanogenesis of human melanocytes with UV exposure, we evaluated the effects of melanogenesis, cellular cycle, intracellular reactive oxidative species (ROS) level and protein level of melanogenic enzyme in cultured human melanocytes following UV-irradiation by OPCs. After treatment with different doses of OPCs or L-ascorbic acid, normal human melanocytes (NHM) were irradiated by 15 mJ/cm2 UV light. Then, cellular melanin content, activity of tyrosinase were examined. Moreover, the protein analysis of tyrosinase, tyrosinase related protein 1 (TRP1), and tyrosinase related protein 2 (TRP2) were observed by Western blotting. Levels of UV-induced ROS in melanocytes and the responses of cell cycle were also examined by immunofluorescence techniques. This study demonstrated that OPCs, significantly inhibited the cell dead induced by UV irradiation in a dose-dependent manner and OPCs alone, has no effects on melanogenesis of NHM, however, it significantly inhibited UV-induced melanogenesis in a dose-dependent manner. The UV-induced intracellular ROS enhancement was also prevented by addition of OPCs in a dose-dependent manner. Meanwhile, OPCs also inhibited the extent of G1 arrest that was induced by UV exposure. OPCs can decrease the protein level of tyrosinase, TRP1 and TRP2 in UV-irradiated NHM. Thus, OPCs have potential effects of photoprotection on human melanocytes by improving cell viability, scavenging intracellular ROS, adjusting cell cycle and inhibiting protein expression of melanogenic enzymes.