Prediction of lymphovascular invasion of gastric cancer based on contrast-enhanced computed tomography radiomics.

Background: Lymphovascular invasion (LVI) is a significant risk factor for lymph node metastasis in gastric cancer (GC) and is closely related to the prognosis and recurrence of GC. This study aimed to establish clinical models, radiomics models and combination models for the diagnosis of GC vascular invasion. Methods: This study enrolled 146 patients with GC proved by pathology and who underwent radical resection of GC. The patients were assigned to the training and validation cohorts. A total of 1,702 radiomic features were extracted from contrast-enhanced computed tomography images of GC. Logistic regression analyses were performed to establish a clinical model, a radiomics model and a combined model. The performance of the predictive models was measured by the receiver operating characteristic (ROC) curve. Results: In the training cohort, the age of LVI negative (-) patients and LVI positive (+) patients were 62.41 ± 8.41 and 63.76 ± 10.08 years, respectively, and there were more male (n = 63) than female (n = 19) patients in the LVI (+) group. Diameter and differentiation were the independent risk factors for determining LVI (-) and (+). A combined model was found to be relatively highly discriminative based on the area under the ROC curve for both the training (0.853, 95% CI: 0.784-0.920, sensitivity: 0.650 and specificity: 0.907) and the validation cohorts (0.742, 95% CI: 0.559-0.925, sensitivity: 0.736 and specificity: 0.700). Conclusions: The combined model had the highest diagnostic effectiveness, and the nomogram established by this model had good performance. It can provide a reliable prediction method for individual treatment of LVI in GC before surgery.

Comparative Efficacy of Novel Biologics, Antitumour Necrosis Factor Agents, and Immunomodulators to Prevent Postoperative Recurrence in Crohn's Disease: A Systematic Review and Network Meta-analysis.

BACKGROUND AND AIMS: Our objective was to compare the efficacy of novel biologics (like vedolizumab and ustekinumab), anti-tumour necrosis factor agents (anti-TNFs), and immunomodulators (IMMs) in preventing postoperative recurrence (POR) of Crohn's disease (CD). METHODS: We searched PubMed, Embase, and the Cochrane Library databases up to December 2023 to identify placebo-controlled, no-treatment-comparison, or positive-controlled studies for the prevention of POR in CD. Endoscopic and clinical recurrence were the primary and secondary endpoint for the efficacy assessment. We conducted traditional direct and Bayesian network meta-analyses to evaluate the preventive effects of selected drugs. Additionally, we ranked interventions based on their scores under the Surface Under the Cumulative Ranking curve (SUCRA). RESULTS: A total of 17 studies involving 2786 patients were included. In the direct meta-analysis, anti-TNFs, vedolizumab, and IMMs showed greater efficacy in preventing endoscopic POR, compared to controls (placebo or no treatment). When it came to preventing clinical POR, anti-TNFs and IMMs outperformed controls. The network meta-analysis revealed that the risk of endoscopic POR was considerably lower in patients receiving anti-TNFs, vedolizumab, and ustekinumab compared to controls. Regarding the reduction of clinical POR, only anti-TNFs showed significant efficacy compared to controls. Vedolizumab and anti-TNFs were ranked as the most effective strategies in preventing endoscopic and clinical recurrence, respectively. CONCLUSIONS: According to direct and network meta-analysis, in CD patients after surgical resection, novel biologics, especially vedolizumab, were quite effective in decreasing the risk of endoscopic POR, whereas anti-TNFs appeared to perform best in reducing the risk of clinical POR.

Effectiveness and safety of brucea javanica oil assisted TACE versus TACE in the treatment of liver cancer: a systematic review and meta-analysis of randomized controlled trials.

Background: The effectiveness and safety of using Brucea javanica oil (BJO) in combination with Transarterial Chemoembolization (TACE) for liver cancer treatment are subjects of debate. This study aims to assess the comparative effectiveness and safety of BJO-assisted TACE versus TACE alone and quantifies the differences between these two treatment methods. Methods: A systematic search was conducted in multiple databases including PubMed, Cochrane, CNKI, and Wanfang, until 1 July 2023. Meta-analysis was conducted, and the results were presented as mean difference (MD), risk ratio (RR), and 95% confidence intervals (CI). Results: The search yielded 11 RCTs, with a combined sample size of 1054 patients. Meta-analysis revealed that BJO-assisted TACE exhibited superior outcomes compared to standalone TACE. Specific data revealed that BJO-assisted TACE improves clinical benefit rate by 22% [RR = 1.22, 95% CI (1.15, 1.30)], increases the number of people with improved quality of life by 32%, resulting in an average score improvement of 9.53 points [RR = 1.32, 95% CI (1.22, 1.43); MD = 9.53, 95% CI (6.95, 12.10)]. Furthermore, AFP improvement rate improved significantly by approximately 134% [RR = 2.34, 95% CI (1.58, 3.46)], accompanied by notable improvements in liver function indicators, with an average reduction of 27.19 U/L in AST [MD = -27.19, 95% CI (-40.36, -14.02)], 20.77 U/L in ALT [MD = -20.77, 95% CI (-39.46, -2.08)], 12.17 µmol/L in TBIL [MD = -12.17, 95% CI (-19.38, -4.97)], and a decrease of 43.72 pg/mL in VEGF [MD = -43.72, 95% CI (-63.29, -24.15)]. Most importantly, there was a 29% reduction in the occurrence of adverse reactions [RR = 0.71, 95% CI (0.60, 0.84)]. Conclusion: These findings indicate that BJO-assisted TACE may be considered as a potentially beneficial treatment option for liver cancer patients when compared to standalone TACE. It appears to contribute to improved treatment outcomes, enhanced quality of life, and potentially reduced adverse reactions, suggesting it warrants further investigation as a promising approach for liver cancer treatment. Systematic Review Registration: identifier CRD42023428948.

Bridging the gap in managing dry eye disease: a consensus report by the Taiwan society of cataract and refractive surgeons.

BACKGROUND: An impaired ocular surface presents substantial challenges in terms of planning for cataract surgery. As a multifactorial ocular disorder, dry eye disease (DED) is common in the general population and prevalent in patients scheduled for lens replacement surgery. Cataract surgery can exacerbate DED and worsen several ocular parameters. Timely diagnosis and appropriate treatment of DED are vital to ensuring positive ophthalmic surgical outcomes. This consensus report of the Taiwan Society of Cataract and Refractive Surgeons (TSCRS) regarding the management of DED before, during, and after cataract surgery highlights the gaps between clinical guidelines and several aspects of DED, including diagnostic testing, diagnostic criteria, and clinical practice treatment. METHODS: An expert panel of five specialists in the field of ophthalmology was recruited to develop consensus statements regarding the management of DED in both the general population and in patients undergoing cataract surgery in Taiwan. Two separate meetings of the five specialists, who were endorsed by the TSCRS, were convened for this purpose. A survey questionnaire consisting of binary or multiple-choice questions was developed through a consensus-driven formulation process. A percentage value was calculated for each statement, and a minimum of 60% agreement (equivalent to three out of five members) was required to achieve consensus. The second discussion meeting involved the presentation of the finalized consensus statements and concluded the consensus development process. Lastly, the finalized consensus statements were approved by all the experts, and the formulated recommendations for DED in the general population and prospective cataract surgery patients were accordingly presented. RESULTS: The optimal algorithm for managing DED in the general population and in patients scheduled for cataract surgery was developed to address the unmet needs of this cohort in Taiwan. CONCLUSION: This report provides recommendations for managing dry eye disease. It is essential to screen and confirm DED through endorsed questionnaires and tests and then diagnose it. Treatment and management of DED should follow a stepwise approach. Screening and diagnosing DED is also recommended before cataract surgery. After cataract surgery, relatively aggressive treatment strategies are recommended to manage DED effectively.

Biomechanical Analysis of Adjacent Segments after Spinal Fusion Surgery Using a Geometrically Parametric Patient-Specific Finite Element Model.

This study aimed to perform a mechanical analysis of adjacent segments after spinal fusion surgery using a geometrically parametric patient-specific finite element model to elucidate the mechanism of adjacent segment degeneration (ASD), thereby providing theoretical evidence for early disease prevention. Fourteen parameters based on patient-specific spinal geometry were extracted from a patient's preoperative computed tomography (CT) scan, and the relative positions of each spinal segment were determined using the image match method. A preoperative patient-specific model of the spine was established through the above method. The postoperative model after L4-L5 posterior lumbar interbody fusion (PLIF) surgery was constructed using the same method except that the lamina and intervertebral disc were removed, and a cage, 4 pedicle screws, and 2 connecting rods were inserted. Range of motion (ROM) and stress changes were determined by comparing the values of each anatomical structure between the preoperative and postoperative models. The overall ROM of the lumbar spine decreased after fusion, while the ROM, stress in the facet joints, and stress in the intervertebral disc of adjacent segments all increased. An analysis of the stress distribution in the annulus fibrosus, nucleus pulposus, and facet joints also showed that not only was the maximum stress in these tissues elevated, but the areas of moderate-to-high stress were also expanded. During torsion, the stress in the facet joints and annulus fibrosus of the proximal adjacent segment (L3-L4) increased to a larger extent than that in the distal adjacent segment (L5-S1). While fusion surgery causes an overall restriction of motion in the lumbar spine, it also causes more load sharing by the adjacent segments to compensate for the fused segment, thus increasing the risk of ASD. The proximal adjacent segment is more prone to degeneration than the distal adjacent segment after spinal fusion due to the significant increase in stress.

Protective Effects of Danmu Extract Syrup on Acute Lung Injury Induced by Lipopolysaccharide in Mice through Endothelial Barrier Repair.

OBJECTIVE: To investigate the effects of Danmu Extract Syrup (DMS) on lipopolysaccharide (LPS)-induced acute lung injury (ALI) in mice and explore the mechanism. METHODS: Seventy-two male Balb/C mice were randomly divided into 6 groups according to a random number table (n=12), including control (normal saline), LPS (5 mg/kg), LPS+DMS 2.5 mL/kg, LPS+DMS 5 mL/kg, LPS+DMS 10 mL/kg, and LPS+Dexamethasone (DXM, 5 mg/kg) groups. After pretreatment with DMS and DXM, the ALI mice model was induced by LPS, and the bronchoalveolar lavage fluid (BALF) were collected to determine protein concentration, cell counts and inflammatory cytokines. The lung tissues of mice were stained with hematoxylin-eosin, and the wet/dry weight ratio (W/D) of lung tissue was calculated. The levels of tumor necrosis factor-α (TNF-α), interleukin (IL)-6 and IL-1 ß in BALF of mice were detected by enzyme linked immunosorbent assay. The expression levels of Claudin-5, vascular endothelial (VE)-cadherin, vascular endothelial growth factor (VEGF), phospho-protein kinase B (p-Akt) and Akt were detected by Western blot analysis. RESULTS: DMS pre-treatment significantly ameliorated lung histopathological changes. Compared with the LPS group, the W/D ratio and protein contents in BALF were obviously reduced after DMS pretreatment (P<0.05 or P<0.01). The number of cells in BALF and myeloperoxidase (MPO) activity decreased significantly after DMS pretreatment (P<0.05 or P<0.01). DMS pre-treatment decreased the levels of TNF-α, IL-6 and IL-1 ß (P<0.01). Meanwhile, DMS activated the phosphoinositide 3-kinase/protein kinase B (PI3K/Akt) pathway and reversed the expressions of Claudin-5, VE-cadherin and VEGF (P<0.01). CONCLUSIONS: DMS attenuated LPS-induced ALI in mice through repairing endothelial barrier. It might be a potential therapeutic drug for LPS-induced lung injury.

Decoding tumor stage by peritumoral and intratumoral radiomics in resectable esophageal squamous cell carcinoma.

PURPOSE: To evaluate the potential application of radiomics in predicting Tumor-Node-Metastasis (TNM) stage in patients with resectable esophageal squamous cell carcinoma (ESCC). METHODS: This retrospective study included 122 consecutive patients (mean age, 57 years; 27 women). Corresponding tumor of interest was identified on axial arterial-phase CT images with manual annotation. Radiomics features were extracted from intra- and peritumoral regions. Features were pruned to train LASSO regression model with 93 patients to construct a radiomics signature, whose performance was validated in a test set of 29 patients. Prognostic value of radiomics-predicted TNM stage was estimated by survival analysis in the entire cohort. RESULTS: The radiomics signature incorporating one intratumoral and four peritumoral features was significantly associated with TNM stage. This signature discriminated tumor stage with an area under curve (AUC) of 0.823 in the training set, with similar performance in the test set (AUC 0.813). Recurrence-free survival (RFS) was significantly different between different radiomics-predicted TNM stage groups (Low-risk vs high-risk, log-rank P = 0.004). Univariate and multivariate Cox regression analyses revealed that radiomics-predicted TNM stage was an independent preoperative factor for RFS. CONCLUSIONS: The proposed radiomics signature combing intratumoral and peritumoral features was predictive of TNM stage and associated with prognostication in ESCC.

Investigation of corneal epithelial thickness and irregularity by optical coherence tomography after transepithelial photorefractive keratectomy.

CLINICAL RELEVANCE: Corneal epithelial healing after refractive surgery is a clinically significant issue, especially for surface ablation procedures, and this can be monitored using optical coherence tomography (OCT). BACKGROUND: The aim of this work is to investigate the corneal epithelial thickness and irregularity by OCT after transepithelial photorefractive keratectomy (t-PRK) and analyse its correlation with visual and refractive outcomes. METHODS: Patients aged ≥18 years with myopia, with or without astigmatism, who underwent t-PRK between May 2020 and August 2021 were included. All participants were subjected to complete ophthalmic examinations and OCT pachymetry at every follow-up visit. Patients were followed up at 1 week and 1, 3, and 6 months postoperatively. RESULTS: A total of 67 patients (126 eyes) were enrolled in this study. One month postoperatively, spherical equivalent refraction and visual acuity achieved preliminary stability. However, central corneal epithelial thickness (CCET) and standard deviation of the corneal epithelial thickness (SDcet) took 3-6 months to progressive recovery. Patients with higher baseline spherical equivalent refraction were associated with slower epithelial recovery. At every follow-up time point, a significant superior-inferior difference in the minimum corneal epithelial thickness area was observed. Higher stromal haze was correlated with higher spherical equivalent refraction (both baseline and residual) but had no relation with visual outcomes. There was a significant correlation between higher CCET with a better uncorrected distance visual acuity and lower corneal epithelial thickness irregularity. CONCLUSIONS: CCET and SDcet measured by OCT seem to be a good auxiliary indicator for reflecting the status of corneal wound recovery after t-PRK surgery. However, a well-designed randomised control study is needed to confirm the study results.

Multimodal Imaging Features and Prognosis of Metaplastic Breast Carcinoma.

RATIONALE AND OBJECTIVES: Metaplastic breast carcinoma (MBC) is an infrequent malignancy with an unfavorable prognosis, and there is a paucity of research on the multimodal imaging features of MBC. This study aimed to provide a comprehensive analysis of the multimodal imaging features, clinicopathological characteristics, and prognosis of MBC. MATERIALS AND METHODS: A total of 36 patients with histologically confirmed MBC from 2012 to 2021 were included in the study. We analyzed the pre-treatment multimodal imaging features, including mammography, ultrasonography (US), and magnetic resonance imaging (MRI), as well as clinicopathology and prognosis of MBC. Follow-up data included local recurrence, distant metastasis, and overall survival (OS) rate. RESULTS: MBC patients had a median age of 51 years at diagnosis. The most common histologic subtype was squamous cell carcinoma, with 86.1% of MBC being histological grade 3 and triple negative. The most common mammographic findings were irregular shape, non-calcification, and high density. The predominant US findings included irregular shape, parallel orientation, posterior acoustic enhancement, and hypoecho. On MRI, most masses exhibited irregular shape, spiculate margin, heterogeneous enhancement, Type II time intensity curve, and diffusion restriction on diffusion weighted images determined by apparent diffusion coefficient. According to breast imaging reporting and data system, mammography suggested malignancy in 50% of cases, US indicated a moderate to high suspicion of malignancy in 77.8% of cases, MRI revealed malignancy in all cases. At a median follow-up time of 48 months (range, 8-122 months) for 35 MBC patients, the local recurrence, distant metastasis, and OS rates were 11.4%, 28.6%, and 67.4%, respectively. CONCLUSION: The benign features of MBC on mammography and US may cause misinterpretation. However, the inclusion of malignant features observed on MRI can improve diagnostic accuracy.

Antiviral, antioxidant, and anti-inflammatory activities of rhein against white spot syndrome virus infection in red swamp crayfish (Procambarus clarkii).

IMPORTANCE: Aquaculture is essential for ensuring global food security by providing a significant source of animal protein. However, the spread of the white spot syndrome virus (WSSV) has resulted in considerable economic losses in crustacean industries. In this study, we evaluated the antiviral activity of rhein, the primary bioactive component of Rheum palmatum L., against WSSV infection, and many pathological aspects of WSSV were also described for the first time. Our mechanistic studies indicated that rhein effectively arrested the replication of WSSV in crayfish by modulating innate immunity to inhibit viral gene transcription. Furthermore, we observed that rhein attenuated WSSV-induced oxidative and inflammatory stresses by regulating the expression of antioxidant and anti-inflammatory-related genes while enhancing innate immunity by reducing total protein levels and increasing phosphatase activity. Our findings suggest that rhein holds great promise as a potent antiviral agent for the prevention and treatment of WSSV in aquaculture.

Prevalence of meibomian gland dysfunction at a tertiary centre in Taiwan.

CLINICAL RELEVANCE: Meibomian gland dysfunction and dry eye disease are closely related conditions that often coexist and can contribute to the development of each other. Understanding the similarities and differences between these diseases can assist clinicians in implementing effective treatments for both conditions in a clinical setting. BACKGROUND: Dry eye disease is a multifactorial disease of the tears and ocular surface. This study aimed to evaluate the demographic characteristics of patients with meibomian gland dysfunction in Taiwan, investigate the association between meibomian gland dysfunction and dry eye parameters, and estimate the prevalence of meibomian gland dysfunction among patients with dry eye symptoms at a tertiary referral centre. METHODS: This cross-sectional study enrolled patients aged ≥20 years who complained of dry eye symptoms and visited a tertiary centre between September 2019 and March 2020. The patients completed the Ocular Surface Disease Index and Standard Patient Evaluation of Eye Dryness questionnaires before undergoing ocular examination. The lipid layer thickness and meiboscale scores were recorded. In addition, the study measured tear film break-up time, examined corneal staining, and evaluated the number of meibomian glands yielding liquid secretions using a slit lamp. RESULTS: The study evaluated 202 eyes of 202 patients with a mean age of 58.05 ± 13.34 years. The prevalence of meibomian gland dysfunction was 93%. Mean meiboscale score and age were negatively associated, and tear film break-up time was positively associated with the mean number of meibomian glands yielding liquid secretions. Hyperlipidaemia and smoking were the main risk factors for Meibomian gland dysfunction. CONCLUSIONS: The prevalence of meibomian gland dysfunction among patients with dry eye symptoms was extremely high at the tertiary centre, highlighting the strong relationship between Meibomian gland dysfunction and dry eye disease. Clinicians should consider meibomian gland dysfunction as a possible cause of dry eye.

Symptoms of anxiety and depression associated with steroid efficacy and clinical outcomes in patients with inflammatory bowel disease.

Background: Anxiety and depression symptoms are very common in patients with inflammatory bowel disease (IBD). We aimed to explore the impact of anxiety and depression on the efficacy of medications, as well as IBD-related poor outcomes. Method: This was a prospective longitudinal observational study. Hospital Anxiety and Depression Scale was used to assess anxiety and depression symptoms. Logistic regression analyses were used to assess the association between anxiety/depression and the response to different medications. Kaplan-Meier survival analysis and Cox regression model were applied to analyze the relationship between anxiety/depression and IBD-related poor outcomes, which were defined as urgent IBD-related hospitalization, IBD-related surgery, or death. Results: A total of 325 IBD patients were enrolled, 118 of whom were treated with corticosteroids, 88 with azathioprine/6-mercaptopurine (AZA/6-MP), and 147 with anti-TNF agents. Anxiety/depression symptoms were found to be significantly related to steroid resistance, but independent of AZA/6-MP and anti-TNF agents nonresponse. There was a significant association between anxiety/depression symptoms and IBD-related poor outcomes. Coexisting with anxiety/depression symptoms was an independent influencing factor of steroid resistance and IBD-related poor outcomes. Conclusion: IBD patients with anxiety/depression symptoms were at a higher risk of developing steroid resistance and IBD-related poor outcomes. Future studies are needed to explore whether interventions for anxiety and depression will improve their response to medications and change their prognosis.

Anesthesia management in a pediatric patient with complicatedly difficult airway: A case report.

BACKGROUND: Reports on perioperative anesthesia management in pediatric patients with difficult airways are scarce. In addition to relatively more difficulties in the technique of endotracheal intubation, the time for manipulation is restricted compared to adults. Securing the airways safely and avoiding the occurrence of hypoxemia in these patients are of significance. CASE SUMMARY: A 9-year-old boy with spastic cerebral palsy, severe malnutrition, thoracic scoliosis, thoracic and airway malformation, laryngomalacia, pneumonia, and epilepsy faced the risk of anesthesia during palliative surgery. After a thorough preoperative evaluation, a detailed scheme for anesthesia and a series of intubation tools were prepared by a team of anesthesiologists. Awake fiberoptic intubation is the widely accepted strategy for patients with anticipated difficult airways. Given the age and medical condition of the patient, we kept him sedated with spontaneous breathing during endotracheal intubation. The endotracheal intubation was completed on the second attempt after the failure of the first effort. Fortunately, the surgery was successful without postoperative complications. CONCLUSION: Dealing with difficult airways in the pediatric population, proper sedation allows time to intubate without interrupting spontaneous breathing. The appropriate endotracheal intubation method based on the patient's unique characteristics is the key factor in successful management of these rare cases.

Changes in dynamic and static brain fluctuation distinguish minimal hepatic encephalopathy and cirrhosis patients and predict the severity of liver damage.

Purpose: Minimal hepatic encephalopathy (MHE) is characterized by mild neuropsychological and neurophysiological alterations that are not detectable by routine clinical examination. Abnormal brain activity (in terms of the amplitude of low-frequency fluctuation (ALFF) has been observed in MHE patients. However, little is known concerning temporal dynamics of intrinsic brain activity. The present study aimed to investigate the abnormal dynamics of brain activity (dynamic ALFF; dALFF) and static measures [static ALFF; (sALFF)] in MHE patients and to strive for a reliable imaging neuromarkers for distinguishing MHE patients from cirrhosis patients. In addition, the present study also investigated whether intrinsic brain activity predicted the severity of liver damage. Methods: Thirty-four cirrhosis patients with MHE, 28 cirrhosis patients without MHE, and 33 age-, sex-, and education-matched healthy controls (HCs) underwent resting-state magnetic resonance imaging (rs-fMRI). dALFF was estimated by combining the ALFF method with the sliding-window method, in which temporal variability was quantized over the whole-scan timepoints and then compared among the three groups. Additionally, dALFF, sALFF and both two features were utilized as classification features in a support vector machine (SVM) to distinguish MHE patients from cirrhosis patients. The severity of liver damage was reflected by the Child-Pugh score. dALFF, sALFF and both two features were used to predict Child-Pugh scores in MHE patients using a general linear model. Results: Compared with HCs, MHE patients showed significantly increased dALFF in the left inferior occipital gyrus, right middle occipital gyrus, and right insula; increased dALFF was also observed in the right posterior lobe of the cerebellum (CPL) and right thalamus. Compared with HCs, noMHE patients exhibited decreased dALFF in the right precuneus. In contrast, compared with noMHE patients, MHE patients showed increased dALFF in the right precuneus, right superior frontal gyrus, and right superior occipital gyrus. Furthermore, the increased dALFF values in the left precuneus were positively associated with poor digit-symbol test (DST) scores (r = 0.356, p = 0.038); however, dALFF in the right inferior temporal gyrus (ITG) was negatively associated with the number connection test-A (NCT-A) scores (r = -0.784, p = 0.000). A significant positive correlation was found between dALFF in the left inferior occipital gyrus (IOG) and high blood ammonia levels (r = 0.424, p = 0.012). Notably, dALFF values yielded a higher classification accuracy than sALFF values in distinguishing MHE patients from cirrhosis patients. Importantly, the dALFF values predicted the Child-Pugh score (r = 0.140, p = 0.030), whereas sALFF values did not in the current dataset. Combining two features had high accuracy in classification in distinguishing MHE patients from cirrhotic patients and yielded prediction in the severity of liver damage. Conclusion: These findings suggest that combining dALFF and sALFF features is a useful neuromarkers for distinguishing MHE patients from cirrhosis patients and highlights the important role of dALFF feature in predicting the severity of liver damage in MHE.

Cross-attention multi-branch CNN using DCE-MRI to classify breast cancer molecular subtypes.

Purpose: The aim of this study is to improve the accuracy of classifying luminal or non-luminal subtypes of breast cancer by using computer algorithms based on DCE-MRI, and to validate the diagnostic efficacy of the model by considering the patient's age of menarche and nodule size. Methods: DCE-MRI images of patients with non-specific invasive breast cancer admitted to the Second Affiliated Hospital of Dalian Medical University were collected. There were 160 cases in total, with 84 cases of luminal type (luminal A and luminal B and 76 cases of non-luminal type (HER 2 overexpressing and triple negative). Patients were grouped according to thresholds of nodule sizes of 20 mm and age at menarche of 14 years. A cross-attention multi-branch net CAMBNET) was proposed based on the dataset to predict the molecular subtypes of breast cancer. Diagnostic performance was assessed by accuracy, sensitivity, specificity, F1 and area under the ROC curve (AUC). And the model is visualized with Grad-CAM. Results: Several classical deep learning models were included for diagnostic performance comparison. Using 5-fold cross-validation on the test dataset, all the results of CAMBNET are significantly higher than the compared deep learning models. The average prediction recall, accuracy, precision, and AUC for luminal and non-luminal types of the dataset were 89.11%, 88.44%, 88.52%, and 96.10%, respectively. For patients with tumor size <20 mm, the CAMBNET had AUC of 83.45% and ACC of 90.29% for detecting triple-negative breast cancer. When classifying luminal from non-luminal subtypes for patients with age at menarche years, our CAMBNET model achieved an ACC of 92.37%, precision of 92.42%, recall of 93.33%, F1of 92.33%, and AUC of 99.95%. Conclusions: The CAMBNET can be applied in molecular subtype classification of breasts. For patients with menarche at 14 years old, our model can yield more accurate results when classifying luminal and non-luminal subtypes. For patients with tumor sizes ≤20 mm, our model can yield more accurate result in detecting triple-negative breast cancer to improve patient prognosis and survival.

Depression Exacerbates Dextran Sulfate Sodium-Induced Colitis via IRF5-Mediated Macrophage Polarization.

BACKGROUND AND AIMS: Patients with inflammatory bowel disease (IBD) and concurrent depression are predisposed to severer disease activity and a worse prognosis. Macrophage polarization toward the M1 phenotype may contribute to the exacerbation of IBD with comorbid depression. Moreover, interferon regulatory factor 5 (IRF5) is involved in the pathogenesis of IBD. The aim of this study was to explore the role of IRF5 in macrophage polarization in the impact of depression upon colitis. METHODS: Depressive-like behavior was induced by repeated forced swim stress. Colon length, disease activity index (DAI), colon morphology, histology, ultrastructure of epithelial barrier, lamina propria macrophage polarization, and expression of IRF5 were compared between DSS colitis rats with and without depressive-like behavior. IRF5 shRNA was constructed to affect the rat peritoneal macrophages polarization in vitro. After IRF5 shRNA lentivirus was introduced into colon by enema, the colitis severity, lamina propria macrophage polarization, and TNF-α, IL-1ß, and IL-10 of colon tissues were measured. RESULTS: The study found severer colonic inflammation in depressed versus non-depressed DSS-colitis rats. Depressed DSS-colitis rats exhibited smaller subepithelial macrophages size and reduced intracellular granule diversity compared with nondepressed DSS-colitis rats. Increased polarization toward the M1 phenotype, elevated expression of IRF5, and co-expression of IRF5 with CD86 were found in depressed versus nondepressed DSS-colitis rats. Lentivirus-mediated shRNA interference with IRF5 expression switched rat peritoneal macrophage polarization from the M1 to the M2 phenotype, downregulated TNF-α, IL-1ß expression to a greater extent in depressed versus nondepressed colitis rats. CONCLUSIONS: IRF5-mediated macrophage polarization may likely underlie the deterioration of DSS-induced colitis caused by depression.

KAP1 phosphorylation promotes the survival of neural stem cells after ischemia/reperfusion by maintaining the stability of PCNA.

AIMS: To explore the function of phosphorylation of KAP1 (p-KAP1) at the serine-824 site (S824) in the proliferation and apoptosis of endogenous neural stem cells (NSCs) after cerebral ischemic/reperfusion (I/R). METHODS: The apoptosis and proliferation of C17.2 cells transfected with the p-KAP1-expression plasmids and the expression of proliferation cell nuclear antigen (PCNA) and p-KAP1 were detected by immunofluorescence and Western blotting after the Oxygen Glucose deprivation/reperfusion model (OGD/R). The interaction of p-KAP1 and CUL4A with PCNA was analyzed by immunoprecipitation. In the rats MCAO model, we performed the adeno-associated virus (AAV) 2/9 gene delivery of p-KAP1 mutants to verify the proliferation of endogenous NSCs and the colocalization of PCNA and CUL4A by immunofluorescence. RESULTS: The level of p-KAP1 was significantly down-regulated in the stroke model in vivo and in vitro. Simulated p-KAP1(S824) significantly increased the proliferation of C17.2 cells and the expression of PCNA after OGD/R. Simulated p-KAP1(S824) enhanced the binding of p-KAP1 and PCNA and decreased the interaction between PCNA and CUL4A in C17.2 cells subjected to OGD/R. The AAV2/9-mediated p-KAP1(S824) increased endogenous NSCs proliferation, PCNA expression, p-KAP1 binding to PCNA, and improved neurological function in the rat MCAO model. CONCLUSIONS: Our findings confirmed that simulated p-KAP1(S824) improved the survival and proliferation of endogenous NSCs. The underlying mechanism is that highly expressed p-KAP1(S824) promotes binding to PCNA, and inhibits the binding of CUL4A to PCNA. This reduced CUL4A-mediated ubiquitination degradation to increase the stability of PCNA and promote the survival and proliferation of NSCs.

Venlafaxine as an Adjuvant Therapy for Inflammatory Bowel Disease Patients With Anxious and Depressive Symptoms: A Randomized Controlled Trial.

Background and Aims: The effect of antidepressant therapy on Inflammatory Bowel Disease (IBD) remains controversial. This trial aimed to assess whether adding venlafaxine to standard therapy for IBD improved the quality of life (QoL), mental health, and disease activity of patients with IBD with anxious and depressive symptoms. Methods: A prospective, randomized, double-blind, and placebo-controlled clinical trial was conducted. Participants diagnosed with IBD with symptoms of anxiety or depression were randomly assigned to receive either venlafaxine 150 mg daily or equivalent placebo and followed for 6 months. Inflammatory Bowel Disease Questionnaire (IBDQ), Mayo score, Crohn's disease activity index (CDAI), Hospital Anxiety and Depression Scale (HADS), and blood examination were completed before the enrollment, during, and after the follow-up. Mixed linear models and univariate analyses were used to compare groups. Results: Forty-five patients with IBD were included, of whom 25 were randomized to receive venlafaxine. The mean age was 40.00 (SD = 13.12) years old and 25 (55.6%) were male. Venlafaxine showed a significant improvement on QoL (p < 0.001) and disease course (p = 0.035), a greater reduction in HADS (anxiety: p < 0.001, depression: p < 0.001), Mayo scores (p < 0.001), and CDAI (p = 0.006) after 6 months. Venlafaxine had no effect on IL-10 expression, endoscopic scores, relapse rate, and use rate of biologics and corticosteroids, but did reduce serum level of erythrocyte estimation rate (ESR; p = 0.003), C-reactive protein (CRP; p < 0.001) and tumor necrosis factor-α (TNF-α; p = 0.009). Conclusions: Venlafaxine has a significantly beneficial effect on QoL, IBD activity, and mental health in patients with IBD with comorbid anxious or depressive symptoms. (Chinese Clinical Trial Registry, ID: ChiCTR1900021496).

Development and validation of a computed tomography-based immune ecosystem diversity index as an imaging biomarker in non-small cell lung cancer.

OBJECTIVES: To date, there are no data on the noninvasive surrogate of intratumoural immune status that could be prognostic of survival outcomes in non-small cell lung cancer (NSCLC). We aimed to develop and validate the immune ecosystem diversity index (iEDI), an imaging biomarker, to indicate the intratumoural immune status in NSCLC. We further investigated the clinical relevance of the biomarker for survival prediction. METHODS: In this retrospective study, two independent NSCLC cohorts (Resec1, n = 149; Resec2, n = 97) were included to develop and validate the iEDI to classify the intratumoural immune status. Paraffin-embedded resected specimens in Resec1 and Resec2 were stained by immunohistochemistry, and the density percentiles of CD3+, CD4+, and CD8+ T cells to all cells were quantified to estimate intratumoural immune status. Then, EDI features were extracted using preoperative computed tomography to develop an imaging biomarker, called iEDI, to determine the immune status. The prognostic value of iEDI was investigated on NSCLC patients receiving surgical resection (Resec1; Resec2; internal cohort Resec3, n = 419; external cohort Resec4, n = 96; and TCIA cohort Resec5, n = 55). RESULTS: iEDI successfully classified immune status in Resec1 (AUC 0.771, 95% confidence interval [CI] 0.759-0.783; and 0.770 through internal validation) and Resec2 (0.669, 0.647-0.691). Patients with higher iEDI-score had longer overall survival (OS) in Resec3 (unadjusted hazard ratio 0.335, 95%CI 0.206-0.546, p < 0.001), Resec4 (0.199, 0.040-1.000, p < 0.001), and TCIA (0.303, 0.098-0.944, p = 0.001). CONCLUSIONS: iEDI is a non-invasive surrogate of intratumoural immune status and prognostic of OS for NSCLC patients receiving surgical resection. KEY POINTS: • Decoding tumour immune microenvironment enables advanced biomarkers identification. • Immune ecosystem diversity index characterises intratumoural immune status noninvasively. • Immune ecosystem diversity index is prognostic for NSCLC patients.

Notch1 signaling contributes to TLR4-triggered NF-κB activation in macrophages.

Macrophages substantially influence the development, progression, and complications of inflammation-driven diseases. Although numerous studies support the critical role of Notch signaling in most inflammatory diseases, there is limited data on the role of Notch signaling in TLR4-induced macrophage activation and interaction of Notch signaling with other signaling pathways in macrophages during inflammation, such as the NF-κB pathway. This study confirmed that stimulation with lipopolysaccharide (LPS), a TLR4 ligand, upregulated Notch1 expression in monocyte/macrophage-like RAW264.7 cells and bone marrow-derived macrophages (BMDMs). LPS also induced increased mRNA expression of Notch target genes Notch1 and Hes1 in macrophages, suggesting that TLR4 signaling enhances activation of the Notch pathway. The upregulation of Notch1, Notch1 intracellular domain (NICD), and Hes1 proteins by LPS treatment was inhibited by DAPT, a Notch1 inhibitor. Additionally, the increased TNF-α, IL-6, and IL-1ß expression induced by LPS was inhibited by DAPT and rescued by jagged1, a Notch1 ligand. Furthermore, suppression of Notch signaling by DAPT upregulated Cylindromatosis (CYLD) expression but downregulated TRAF6 expression, IκB kinase (IKK) α/ß phosphorylation, and subsequently, phosphorylation and degradation of IκB-α, indicating that DAPT inhibited NF-κB activation triggered by TLR-4. Interestingly, DAPT did not inhibit the increased MyD88 expression induced by LPS. Our study findings demonstrate that macrophage stimulation via the TLR4 signaling cascade triggers activation of Notch1 signaling, which regulates the expression patterns of genes involved in pro-inflammatory responses by activating NF-κB. This effect may be dependent on the CYLD-TRAF6-IKK pathway. Thus, Notch1 signaling may provide a therapeutic target against infectious and inflammation-driven diseases.