PET/CT Manifestations of a Case of Cavernous Hemangioma Misdiagnosed as Reproductive Tumor.

ABSTRACT: Cavernous hemangioma of mediastinum is a rare, benign tumor originating from vascular endothelial cells. It typically arises in the anterior mediastinum but has also been reported in the posterior mediastinum or the middle mediastinum, and occasionally involves both the anterior and middle compartments. We present the case of a 20-year-old man with a cavernous hemangioma of mediastinum initially misdiagnosed as a reproductive tumor by 18F-FDG PET/CT.

Adrenaline in pulp capping treatment of reversible pulpitis.

BACKGROUND: The role of epinephrine in the treatment of pulp capping in patients with reversible pulpitis is not clear. AIM: To explore the role of epinephrine in the treatment of pulp capping in patients with reversible pulpitis. METHODS: A total of 100 patients with reversible pulpitis who were treated in Anhui Jieshou People's Hospital from January 2020 to December 2021 were included in the study. They were categorized into an observation group (n = 50; treatment with adrenaline) and a control group (n = 50; treatment with zinc oxide eugenol paste). The 24-h postoperative pain, regression time of gingival congestion and redness, clinical efficacy, and incidence of adverse reactions were compared between the groups. Patients were further categorized into the ineffective and effective treatment groups based on clinical efficacy. Logistic multiple regression analysis explored factors affecting the efficacy of pulp capping treatment. RESULTS: A significant difference in 24-h postoperative pain was observed between the groups (P < 0.05), with a higher proportion of grade I pain noted in the observation group than in the control group (P < 0.01). The regression time of gingival congestion and swelling was lower in the observation group (2.61 ± 1.44 d and 2.73 ± 1.36 d, respectively) than in the control group (3.85 ± 1.47 d and 4.28 ± 1.61 d, respectively) (P < 0.05). The 2-wk postoperative total effective rate was lower in the control group (80.00%) than in the observation group (94.00%) (P < 0.05). The incidence of adverse reactions was not significantly different between the control (14.00%) and observation (12.00%) groups (P > 0.05). The proportion of adrenaline usage was lower (P < 0.05) and that of anaerobic digestion by Streptococcus and Fusobacterium nucleatum was higher in the ineffective treatment group than in the effective treatment group (P < 0.05). Logistic multiple regression analysis revealed adrenaline as a protective factor (P < 0.05) and anaerobic digestion by Streptococcus and F. nucleatum as risk factors for pulp capping in reversible pulpitis (P < 0.05). CONCLUSION: Adrenaline demonstrated therapeutic efficacy in pulp capping treatment for reversible pulpitis, reducing pain and improving clinical symptoms safely. It is a protective factor for pulp capping, whereas Streptococcus and F. nucleatum are risk factors. Targeted measures can be implemented to improve clinical efficacy.

18 F-FDG PET/CT of Benign Tracheal Schwannoma.

ABSTRACT: Schwannoma is a benign tumor originating from Schwann cells. It commonly occurs in the head, neck, and extremities, but rarely occurs in the trachea. Tracheal schwannoma is usually asymptomatic. We reported the 18 F-FDG PET/CT findings of a 61-year-old man with bronchoscopically biopsy-proven schwannoma, which presented challenges in differentiation from certain benign tumors and low-grade malignancies in the trachea.

Urinary Endometriosis Misdiagnosed as Ureteral Malignant Tumor by PET/CT: A Case Study.

ABSTRACT: Endometriosis is a chronic inflammatory estrogen-dependent benign disease. It is defined as the endometrium growing outside the uterine cavity and the myometrium. It usually has low FDG uptake but rarely occurs in the ureters. We reported a case of a 47-year-old woman's left ureteral nodule originally misdiagnosed as a ureteral malignant tumor by PET/CT and finally pathologically confirmed as endometriosis.

Cross-sectional imaging: current status and future potential in adult celiac disease.

Celiac disease (CD), triggered by exposure to gluten in genetically susceptible individuals, is an immune-mediated small bowel disease affecting about 1% of the population worldwide. But the prevalence of CD varies with age, sex, and location. A strict gluten-free diet remains the primary treatment for CD, currently. Most of patients with CD respond well to gluten-free diet with good prognosis, while some patients fail to get symptomatic relief or histological remission (e.g., nonresponsive or refractory CD). Because of heterogeneous clinical appearance, the diagnosis of CD is difficult. Moreover, malignant complications and poor outcomes accompanied with refractory CD present great challenges in disease management. Over the past three decades, cross-sectional imaging techniques (computed tomography [CT] and magnetic resonance imaging [MRI]) play an important role in small bowel inflammatory and neoplastic diseases. Compared with endoscopic techniques, cross-sectional imaging permits clearly presentation of both intraluminal and extraluminal abnormalities. It provides vascular and functional information, thus improving the possibility as diagnostic and follow-up tool. The value of cross-sectional imaging for patients with suspected or confirmed CD has been gradually demonstrated. Studies revealed that certain features suggested by cross-sectional imaging could help to establish the early diagnosis of CD. Besides, the potential contributions of cross-sectional imaging may lie in the evaluation of disease activity and severity, which helps guiding management strategies. The purpose of this review is to provide current overviews and future directions of cross-sectional imaging in adult CD, thus facilitating the understanding and application in clinical practice. CLINICAL RELEVANCE STATEMENT: In this review, we systematically summarized the existing knowledge of cross-sectional imaging in adult CD and analyzed their possible roles in clinical practice, including disease diagnosis, complication identification, treatment evaluation, and prognostic prediction. KEY POINTS: • Regarding a condition described as "celiac iceberg", celiac disease remains underdiagnosed and undertreated. • Cross-sectional imaging is helpful in clinical management of celiac disease, including disease diagnosis, complication identification, treatment evaluation, and prognostic prediction. • Cross-sectional imaging should be considered as the valuable examination in patients suspected from celiac disease.

Pharmacokinetics and safety evaluation of intravenously administered Pseudomonas phage PA_LZ7 in a mouse model.

IMPORTANCE: Phage therapy is gaining traction as an alternative to antibiotics due to the rise of multi-drug-resistant (MDR) bacteria. This study assessed the pharmacokinetics and safety of PA_LZ7, a phage targeting MDR Pseudomonas aeruginosa, in mice. After intravenous administration, the phage showed an exponential decay in plasma and its concentration dropped significantly within 24 h for all dosage groups. Although there was a temporary increase in certain plasma cytokines and spleen weight at higher dosages, no significant toxicity was observed. Therefore, PA_LZ7 shows potential as an effective and safe candidate for future phage therapy against MDR P. aeruginosa infections.

Current perspectives on resistance to chimeric antigen receptor T-cell therapy and strategies to improve efficacy in B-cell lymphoma.

Although chimeric antigen receptor (CAR) T-cell therapy has demonstrated remarkable efficacy in patients with chemo-refractory B-cell lymphoma, a significant portion is refractory or relapse. Resistance is a major barrier to improving treatment efficacy and long-term survival in CAR T-cell therapy, and clinicians have very limited tools to discriminate a priori patients who will or will not respond to treatment. While CD19-negative relapses due to loss of target antigen is well described, it accounts for only about 30% of cases with treatment failure. Recent efforts have shed light on mechanisms of CD19-positive relapse due to tumor intrinsic resistance, T-cell quality/manufacturing, or CAR T-cell exhaustion mediated by hostile tumor microenvironment. Here, we review the latest updates of preclinical and clinical trials to investigate the mechanisms of resistance and relapse post CAR T-cell therapy in B cell lymphoma and discuss novel treatment strategies to overcome resistance as well as advances that are useful for a CAR T therapist to optimize and personalize CAR T-cell therapy.

Factors Affecting Patient and Caregiver Preferences for Treatment of Myeloma and Indolent Lymphoma.

PURPOSE: Treatment options for myeloma and indolent lymphoma are increasing exponentially, with distinct efficacy, side effects, and cost. We aim to determine the factors influencing patient and caregiver treatment preferences. METHODS: Patients and caregivers of patients with myeloma and indolent lymphoma were recruited from two cancer centers in Singapore. Preferences were elicited using a discrete choice experiment. Attributes and levels were selected based on a previous qualitative study. The relative preference for levels within each attribute (part worth utility values) and the extent to which an attribute would influence decision making (relative importance) were calculated. Patient and caregiver participation in the treatment plan selection process were assessed using the Control Preference Scale. RESULTS: One hundred ninety-nine patients and 169 caregivers were recruited. Patients placed the highest importance on out-of-pocket costs (relative importance = 35%), followed by efficacy (25%), persistent side effects (19%), administration route (8%), treatment duration (7%), and short-term side effects (5%). Caregivers ranked efficacy (27%) as the most important attribute, over out-of-pocket costs (24%). Most patients preferred a collaborative role in the shared decision-making process, while similar proportions of caregivers favored active and collaborative roles. CONCLUSION: Our study demonstrates that both patients and caregivers consider cost seriously when making treatment decisions. Furthermore, as patient and caregiver preferences may differ, there are implications for treatment selection and counseling, especially in cultures where caregivers have more prominent roles in treatment planning.

Aberrant degree centrality profiles during rumination in major depressive disorder.

Rumination is closely linked to the onset and maintenance of major depressive disorder (MDD). Prior neuroimaging studies have identified the association between self-reported rumination trait and the functional coupling among a network of brain regions using resting-state functional magnetic resonance imaging (MRI). However, little is known about the underlying neural circuitry mechanism during active rumination in MDD. Degree centrality (DC) is a simple metric to denote network integration, which is critical for higher-order psychological processes such as rumination. During an MRI scan, individuals with MDD (N = 45) and healthy controls (HC, N = 46) completed a rumination state task. We examined the interaction effect between the group (MDD vs. HC) and condition (rumination vs. distraction) on vertex-wise DC. We further characterized the identified brain region's functional involvement with Neurosynth and BrainMap. Network-wise seed-based functional connectivity (FC) analysis was also conducted for the identified region of interest. Finally, exploratory correlation analysis was conducted between the identified region of interest's network FCs and self-reported in-scanner affect levels. We found that a left superior frontal gyrus (SFG) region, generally overlapped with the frontal eye field, showed a significant interaction effect. Further analysis revealed its involvement with executive functions. FCs between this region, the frontoparietal, and the dorsal attention network (DAN) also showed significant interaction effects. Furthermore, its FC to DAN during distraction showed a marginally significant negative association with in-scanner affect level at the baseline. Our results implicated an essential role of the left SFG in the rumination's underlying neural circuitry mechanism in MDD and provided novel evidence for the conceptualization of rumination in terms of impaired executive control.

Effect of smoking on thrombotic antiphospholipid syndrome: a 10-year prospective cohort study.

OBJECTIVES: Cigarette smoking is an established risk factor for autoimmune diseases. However, whether smoking plays a clear role in thrombotic antiphospholipid syndrome (TAPS) has not been determined. We aimed to investigate the effects of smoking on clinical characteristics and prognosis of TAPS. METHODS: This was a prospective cohort study from 2013 to 2022. During the study period, 297 patients were diagnosed with TAPS, including 82 smokers and 215 non-smokers. After propensity score matching, 57 smokers and 57 non-smokers matched by age and sex were analysed. RESULTS: Overall, smokers with TAPS had more cardiovascular risk factors (CVRFs) than non-smokers, including hypertension (36.59% vs. 14.42%, P<0.001), obesity (15.85% vs. 7.44%, P=0.029), dyslipidaemia (64.63% vs. 48.37%, P=0.012), and hyperhomocysteinaemia (62.20% vs. 36.28%, P<0.001). Arterial thrombotic events were more common in smokers at diagnosis (62.20% vs. 46.05%, P=0.013), especially myocardial infarction, visceral thrombosis, and peripheral vascular thrombosis. After matching, smokers showed balanced CVRFs with non-smokers at baseline, but retained a higher prevalence of arterial thrombosis (59.65% vs. 33.33%, P=0.005), mainly distributed in cerebral vascular, cardiovascular, and retinal vascular territories. During follow-up, smokers presented a tendency for more recurrent arterial thrombosis and less recurrent venous thrombosis. Smokers had significantly poorer outcomes for organ damage with higher DIAPS (median, 2.00 vs. 1.00, P=0.008), especially in the cardiovascular (26.32% vs. 3.51%, P=0.001), gastrointestinal (15.79% vs. 1.75%, P=0.016), and ophthalmologic (10.53% vs. 00.00%, P=0.027) systems. CONCLUSION: Smoking is related to increased arterial events and poor prognosis in TAPS patients. Patients with TAPS should be fully encouraged to avoid smoking.

Identification of triple-negative breast cancer and androgen receptor expression based on histogram and texture analysis of dynamic contrast-enhanced MRI.

BACKGROUND: Triple-negative breast cancer (TNBC) is highly malignant and has a poor prognosis due to the lack of effective therapeutic targets. Androgen receptor (AR) has been investigated as a possible therapeutic target. This study quantitatively assessed intratumor heterogeneity by histogram analysis of pharmacokinetic parameters and texture analysis on dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) to discriminate TNBC from non-triple-negative breast cancer (non-TNBC) and to identify AR expression in TNBC. METHODS: This retrospective study included 99 patients with histopathologically proven breast cancer (TNBC: 36, non-TNBC: 63) who underwent breast DCE-MRI before surgery. The pharmacokinetic parameters of DCE-MRI (Ktrans, Kep and Ve) and their corresponding texture parameters were calculated. The independent t-test, or Mann-Whitney U-test was used to compare quantitative parameters between TNBC and non-TNBC groups, and AR-positive (AR+) and AR-negative (AR-) TNBC groups. The parameters with significant difference between two groups were further involved in logistic regression analysis to build a prediction model for TNBC. The ROC analysis was conducted on each independent parameter and the TNBC predicting model for evaluating the discrimination performance. The area under the ROC curve (AUC), sensitivity and specificity were derived. RESULTS: The binary logistic regression analysis revealed that Kep_Range (p = 0.032) and Ve_SumVariance (p = 0.005) were significantly higher in TNBC than in non-TNBC. The AUC of the combined model for identifying TNBC was 0.735 (p < 0.001) with a cut-off value of 0.268, and its sensitivity and specificity were 88.89% and 52.38%, respectively. The value of Kep_Compactness2 (p = 0.049), Kep_SphericalDisproportion (p = 0.049), and Ve_GlcmEntropy (p = 0.008) were higher in AR + TNBC group than in AR-TNBC group. CONCLUSION: Histogram and texture analysis of breast lesions on DCE-MRI showed potential to identify TNBC, and the specific features can be possible predictors of AR expression, enhancing the ability to individualize the treatment of patients with TNBC.

ATM Inhibition-Induced ISG15/IFI27/OASL Is Correlated with Immunotherapy Response and Inflamed Immunophenotype.

Immune checkpoint blockade (ICB) therapy can improve the survival of cancer patients with a high tumor mutation burden (TMB-H) or deficiency in DNA mismatch repair (dMMR) in their tumors. However, most cancer patients without TMB-H and dMMR do not benefit from ICB therapy. The inhibition of ATM can increase DNA damage and activate the interferon response, thus modulating the tumor immune microenvironment (TIME) and the efficacy of ICB therapy. In this study, we showed that ATM inhibition activated interferon signaling and induced interferon-stimulated genes (ISGs) in cisplatin-resistant and parent cancer cells. The ISGs induced by ATM inhibition were correlated with survival in cancer patients who received ICB therapy. In oral cancer, high expressions of ISG15, IFI27, and OASL were associated with low expressions of ATM, the activation of inflamed immune pathways, and increased tumor-infiltrating scores of CD8+ T, natural killer, and dendritic cells. The high expressions of ISG15, IFI27, and OASL were also correlated with complete remission in patients with cervical cancer treated with cisplatin. These results suggest that ATM inhibition can induce the interferon response and inflamed TIME, which may benefit ICB therapy.

Clinical outcome is distinct between radiological stricture and endoscopic stricture in ileal Crohn's disease.

OBJECTIVES: Differences in clinical adverse outcomes (CAO) based on different intestinal stricturing definitions in Crohn's disease (CD) are poorly documented. This study aims to compare CAO between radiological strictures (RS) and endoscopic strictures (ES) in ileal CD and explore the significance of upstream dilatation in RS. METHODS: This retrospective double-center study included 199 patients (derivation cohort, n = 157; validation cohort, n = 42) with bowel strictures who simultaneously underwent endoscopic and radiologic examinations. RS was defined as a luminal narrowing with wall thickening relative to the normal gut on cross-sectional imaging (group 1 (G1)), which further divided into G1a (without upstream dilatation) and G1b (with upstream dilatation). ES was defined as an endoscopic non-passable stricture (group 2 (G2)). Strictures met the definitions of RS (with or without upstream dilatation) and ES were categorized as group 3 (G3). CAO referred to stricture-related surgery or penetrating disease. RESULTS: In the derivation cohort, G1b (93.3%) had the highest CAO occurrence rate, followed by G3 (32.6%), G1a (3.2%), and G2 (0%) (p < 0.0001); the same order was found in the validation cohort. The CAO-free survival time was significantly different among the four groups (p < 0.0001). Upstream dilatation (hazard ratio, 1.126) was a risk factor for predicting CAO in RS. Furthermore, when upstream dilatation was added to diagnose RS, 17.6% of high-risk strictures were neglected. CONCLUSIONS: CAO differs significantly between RS and ES, and clinicians should pay more attention to strictures in G1b and G3. Upstream dilatation has an important impact on the clinical outcome of RS but may not be an essential factor for RS diagnosis. CLINICAL RELEVANCE STATEMENT: This study explored the definition of intestinal stricture with the greatest significance for the clinical diagnosis and prognosis of patients with CD, and consequently provided effective auxiliary information for clinicians to formulate strategies for the treatment of CD intestinal strictures. KEY POINTS: • The retrospective double-center study showed that clinical adverse outcome is different between radiological strictures and endoscopic strictures in CD. • Upstream dilatation has an important impact on the clinical outcome of radiological strictures but may not be an essential factor for diagnosis of radiological strictures. • Radiological stricture with upstream dilatation and simultaneous radiological and endoscopic stricture were at increased risk for clinical adverse outcomes; thus, closer monitoring should be considered.

Effects of Therapist Intervention during Upper-Extremity Robotic Rehabilitation in Patients with Stroke.

This study aimed to determine whether the treatment effect differs for patients with stroke who perform robot-assisted upper-extremity rehabilitation by themselves compared to those whose rehabilitation is actively assisted by a therapist. Stroke patients with hemiplegia were randomly divided into two groups and received robot-assisted upper-limb rehabilitation for four weeks. In the experimental group, a therapist actively intervened in the treatment, while in the control group, the therapist only observed. After four weeks of rehabilitation, the manual muscle strength, Brunnstrom stage, Fugl-Meyer assessment of the upper-extremity (FMA-UE), box and block test, and functional independence measure (FIM) showed significant improvement in both groups compared to that before treatment; however, no interval change in spasticity was noted. The post-treatment values showed that the FMA-UE and box and block tests were significantly improved in the experimental group compared to those in the control group. Comparing the changes in the pre- and post-treatment values, the FMA-UE, box and block test, and FIM of the experimental group were significantly improved compared to those in the control group. Our results suggest that active intervention by therapists during robot-assisted upper-limb rehabilitation positively impacts upper-extremity function outcomes in patients with stroke.

Preoperative computed tomography enterography-based radiomics signature: A potential predictor of postoperative anastomotic recurrence in patients with Crohn's disease.

BACKGROUND: More than half of patients with Crohn's disease (CD) require at least one surgery for symptom management; however, approximately half of the patients may experience postoperative anastomotic recurrence (PAR). OBJECTIVES: This study aims to develop and validate a preoperative computed tomography enterography (CTE)-based radiomics signature to predict early PAR in CD. DESIGN: A total of 186 patients with CD (training cohort, n = 134; test cohort, n = 52) who underwent preoperative CTE and surgery between January 2014 and June 2020 were included in this retrospective multi-centre study. METHODS: 106 radiomic features were initially extracted from intestinal lesions and peri-intestinal mesenteric fat, respectively; significant radiomic features were selected from them and then used to develop intestinal or mesenteric radiomics signatures, using the least absolute shrinkage and selection operator and a Cox regression model. A radiomics-based nomogram incorporating these signatures with clinical-radiological factors was created for comparison with a model based on clinical-radiological features alone. RESULTS: 68 of 134 patients in training cohort and 16 of 52 patients in test cohort suffered from PAR. The intestinal radiomic signature (hazard ratio [HR]: 2.17; 95% confidence interval [CI]: 1.32-3.58; P = 0.002) and mesenteric radiomic signature (HR: 2.19; 95% CI: 1.14-4.19; P = 0.018) were independent risk factors for PAR in the training cohort as per a multivariate analysis. The radiomics-based nomogram (C-index: 0.710; 95% CI: 0.672-0.748) yielded superior predictive performance than the clinical-radiological model (C-index, 0.607; 95% CI: 0.582-0.632) in the test cohort. Decision curve analysis demonstrated that the radiomics-based nomogram outperformed the clinical-radiological model in terms of clinical usefulness. CONCLUSIONS: Preoperative mesenteric and intestinal CTE radiomics signatures are potential non-invasive predictors of PAR in postoperative patients with CD.

Artificial intelligence-based computer-aided diagnosis system supports diagnosis of lymph node metastasis in esophageal squamous cell carcinoma: A multicenter study.

Background: This study aimed to develop an artificial intelligence-based computer-aided diagnosis system (AI-CAD) emulating the diagnostic logic of radiologists for lymph node metastasis (LNM) in esophageal squamous cell carcinoma (ESCC) patients, which contributed to clinical treatment decision-making. Methods: A total of 689 ESCC patients with PET/CT images were enrolled from three hospitals and divided into a training cohort and two external validation cohorts. 452 CT images from three publicly available datasets were also included for pretraining the model. Anatomic information from CT images was first obtained automatically using a U-Net-based multi-organ segmentation model, and metabolic information from PET images was subsequently extracted using a gradient-based approach. AI-CAD was developed in the training cohort and externally validated in two validation cohorts. Results: The AI-CAD achieved an accuracy of 0.744 for predicting pathological LNM in the external cohort and a good agreement with a human expert in two external validation cohorts (kappa = 0.674 and 0.587, p < 0.001). With the aid of AI-CAD, the human expert's diagnostic performance for LNM was significantly improved (accuracy [95% confidence interval]: 0.712 [0.669-0.758] vs. 0.833 [0.797-0.865], specificity [95% confidence interval]: 0.697 [0.636-0.753] vs. 0.891 [0.851-0.928]; p < 0.001) among patients underwent lymphadenectomy in the external validation cohorts. Conclusions: The AI-CAD could aid in preoperative diagnosis of LNM in ESCC patients and thereby support clinical treatment decision-making.

Inhibitory Effect of Resveratrol on LPS-induced Glomerular Mesangial Cells Proliferation and TGF-ß1 Expression via Sphingosine Kinase 1 Pathway.

OBJECTIVE: To elucidate the renoprotective effect of resveratrol (RSV) on sphingosine kinase 1 (SphK1) signaling pathway and expression of its downstream molecules including activator protein 1 (AP-1) and transformation growth factor-ß1 (TGF-ß1) in lipopolysaccharide (LPS)-induced glomerular mesangial cells (GMCs). METHODS: The rat GMCs line (HBZY-1) were cultured and randomly divided into 5 groups, including control, LPS (100 ng/mL), and 5, 10, 20 µmol/L RSV-treated groups. In addition, SphK1 inhibitor (SK-II) was used as positive control. GMCs were pretreated with RSV for 2 h and treated with LPS for another 24 h. GMCs proliferation was determined by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide (MTT) assay. The proteins expression of SphK1, p-c-Jun and TGF-ß1 in GMCs were detected by Western blot, and DNA-binding activity of AP-1 was performed by electrophoretic mobility shift assay (EMSA). The binding activity between RSV and SphK1 protein was detected by AutoDock Vina and visualized by Discovery Studio 2016. RESULTS: LPS could obviously stimulate GMCs proliferation, elevate SphK1, p-c-Jun and TGF-ß1 expression levels and increase the DNA-binding activity of AP-1 (P<0.05 or P<0.01), whereas these effects were significantly blocked by RSV pretreatment. It was also suggested that the effect of RSV was similar to SK-II (P>0.05). Moreover, RSV exhibited good binding affinity towards SphK1, with docking scores of -8.1 kcal/moL and formed hydrogen bonds with ASP-178 and LEU-268 in SphK1. CONCLUSION: RSV inhibited LPS-induced GMCs proliferation and TGF-ß1 expression, which may be independent of its hypoglycemic effect on preventing the development of mesangial cell fibrosis and closely related to the direct inhibition of SphK1 pathway.

Chondroitin polymerizing factor predicts a poor prognosis and promotes breast cancer progression via the upstream TGF-ß1/SMAD3 and JNK axis activation.

Aberrant composition of glycans in the tumor microenvironment (TME) contributes to tumor progression and metastasis. Chondroitin polymerizing factor (CHPF) is a glycosyltransferase that catalyzes the biosynthesis of chondroitin sulfate (CS). It is also correlated to transforming growth factor-ß1 (TGF-ß1) expression, a crucial mediator in the interaction of cancer cells with TME. In this study, we investigated the association of CHPF expression with the clinicopathological features of breast cancer (BRCA), as well the oncogenic effect and the underling mechanisms of CHPF upon BRCA cells. We found that CHPF expression is significantly increased in human BRCA tissues, and it is positively associated with TGF-ß expression (r = 0.7125). The high-expression of CHPF predicts a poor prognosis and is positively correlated with tumor mass, lymph node metastasis, clinical staging and HER-2 negative-expression. The mechanistic study revealed that it promotes BRCA cell proliferation, migration and invasion through TGF-ß1-induced SMAD3 and JNK activation in vitro, JNK (SP600125) or SMAD3 (SIS3) inhibitor can remove the promotion of CHPF upon cell proliferation, migration and invasion in MDA-MB-231 cells, which is derived from triple-negative breast cancer (TNBC). Collectively, our finding suggested CHPF may function as an oncogene and is highly expressed in human BRCA tissues. Pharmacological blockade of the upstream of JNK or SMAD3 signaling may provide a novel therapeutic target for refractory TNBC patients with CHPF abnormal high-expression.

Development and validation of prognostic nomogram for malignant pleural mesothelioma / 中华肿瘤杂志

Objective: To development the prognostic nomogram for malignant pleural mesothelioma (MPM). Methods: Two hundred and ten patients pathologically confirmed as MPM were enrolled in this retrospective study from 2007 to 2020 in the People's Hospital of Chuxiong Yi Autonomous Prefecture, the First and Third Affiliated Hospital of Kunming Medical University, and divided into training (n=112) and test (n=98) sets according to the admission time. The observation factors included demography, symptoms, history, clinical score and stage, blood cell and biochemistry, tumor markers, pathology and treatment. The Cox proportional risk model was used to analyze the prognostic factors of 112 patients in the training set. According to the results of multivariate Cox regression analysis, the prognostic prediction nomogram was established. C-Index and calibration curve were used to evaluate the model's discrimination and consistency in raining and test sets, respectively. Patients were stratified according to the median risk score of nomogram in the training set. Log rank test was performed to compare the survival differences between the high and low risk groups in the two sets. Results: The median overall survival (OS) of 210 MPM patients was 384 days (IQR=472 days), and the 6-month, 1-year, 2-year, and 3-year survival rates were 75.7%, 52.6%, 19.7%, and 13.0%, respectively. Cox multivariate regression analysis showed that residence (HR=2.127, 95% CI: 1.154-3.920), serum albumin (HR=1.583, 95% CI: 1.017-2.464), clinical stage (stage Ⅳ: HR=3.073, 95% CI: 1.366-6.910) and the chemotherapy (HR=0.476, 95% CI: 0.292-0.777) were independent prognostic factors for MPM patients. The C-index of the nomogram established based on the results of Cox multivariate regression analysis in the training and test sets were 0.662 and 0.613, respectively. Calibration curves for both the training and test sets showed moderate consistency between the predicted and actual survival probabilities of MPM patients at 6 months, 1 year, and 2 years. The low-risk group had better outcomes than the high-risk group in both training (P=0.001) and test (P=0.003) sets. Conclusion: The survival prediction nomogram established based on routine clinical indicators of MPM patients provides a reliable tool for prognostic prediction and risk stratification.