A deep learning model based on MRI for prediction of vessels encapsulating tumour clusters and prognosis in hepatocellular carcinoma.

PURPOSE: This study aimed to build and evaluate a deep learning (DL) model to predict vessels encapsulating tumor clusters (VETC) and prognosis preoperatively in patients with hepatocellular carcinoma (HCC). METHODS: 320 pathologically confirmed HCC patients (58 women and 262 men) from two hospitals were included in this retrospective study. Institution 1 (n = 219) and Institution 2 (n = 101) served as the training and external test cohorts, respectively. Tumors were evaluated three-dimensionally and regions of interest were segmented manually in the arterial, portal venous, and delayed phases (AP, PP, and DP). Three ResNet-34 DL models were developed, consisting of three models based on a single sequence. The fusion model was developed by inputting the prediction probability of the output from the three single-sequence models into logistic regression. The area under the receiver operating characteristic curve (AUC) was used to compare performance, and the Delong test was used to compare AUCs. Early recurrence (ER) was defined as recurrence within two years of surgery and early recurrence-free survival (ERFS) rate was evaluated by Kaplan-Meier survival analysis. RESULTS: Among the 320 HCC patients, 227 were VETC- and 93 were VETC+ . In the external test cohort, the fusion model showed an AUC of 0.772, a sensitivity of 0.80, and a specificity of 0.61. The fusion model-based prediction of VETC high-risk and low-risk categories exhibits a significant difference in ERFS rates, akin to the outcomes observed in VETC + and VETC- confirmed through pathological analyses (p < 0.05). CONCLUSIONS: A DL framework based on ResNet-34 has demonstrated potential in facilitating non-invasive prediction of VETC as well as patient prognosis.

A Comprehensive Model Based on Dynamic Contrast-Enhanced Magnetic Resonance Imaging Can Better Predict the Preoperative Histological Grade of Breast Cancer Than a Radiomics Model.

Background: Histological grade is an important prognostic factor for patients with breast cancer and can affect clinical decision-making. From a clinical perspective, developing an efficient and non-invasive method for evaluating histological grading is desirable, facilitating improved clinical decision-making by physicians. This study aimed to develop an integrated model based on radiomics and clinical imaging features for preoperative prediction of histological grade invasive breast cancer. Methods: In this retrospective study, we recruited 211 patients with invasive breast cancer and randomly assigned them to either a training group (n=147) or a validation group (n=64) with a 7:3 ratio. Patients were classified as having low-grade tumors, which included grade I and II tumors, or high-grade tumors, which included grade III tumors. Three models were constructed based on basic clinical features, radiomics features, and the sum of the two. To assess diagnostic performance of the radiomics models, we employed measures such as receiver operating characteristic (ROC) curve, decision curve analysis (DCA), accuracy, sensitivity, and specificity, and the predictive performance of the three models was compared using the DeLong test and net reclassification improvement (NRI). Results: The area under the curve (AUC) of the clinical model, radiomics model, and comprehensive model was 0.682, 0.833, and 0.882 in the training set and 0.741, 0.751, and 0.836 in the validation set, respectively. NRI analysis confirmed that the combined model was better than the other two models in predicting the histological grade of breast cancer (NRI=21.4% in the testing cohort). Conclusion: Compared with the other models, the comprehensive model based on the combination of basic clinical features and radiomics features exhibits more significant potential for predicting histological grade and can better assist clinicians in optimal decision-making.

Effective TME-related signature to predict prognosis of patients with head and neck squamous cell carcinoma.

Introduction: The tumor microenvironment (TME) is crucial for the development of head and neck squamous cell carcinoma (HNSCC). However, the correlation of the characteristics of the TME and the prognosis of patients with HNSCC remains less known. Methods: In this study, we calculated the immune and stromal cell scores using the "estimate" R package. Kaplan-Meier survival and CIBERSORT algorithm analyses were applied in this study. Results: We identified seven new markers: FCGR3B, IGHV3-64, AC023449.2, IGKV1D-8, FCGR2A, WDFY4, and HBQ1. Subsequently, a risk model was constructed and all HNSCC samples were grouped into low- and high-risk groups. The results of both the Kaplan-Meier survival and receiver operating characteristic curve (ROC) analyses showed that the prognosis indicated by the model was accurate (0.758, 0.756, and 0.666 for 1-, 3- and 5-year survival rates). In addition, we applied the CIBERSORT algorithm to reveal the significant differences in the infiltration levels of immune cells between the two risk groups. Discussion: Our study elucidated the roles of the TME and identified new prognostic biomarkers for patients with HNSCC.

Oncogenic BRAF noncanonically promotes tumor metastasis by mediating VASP phosphorylation and filopodia formation.

BRAF is frequently mutated in various cancer types and contributes to tumorigenesis and metastasis. As an important switch in RAS signaling pathway, BRAF typically enables the activation of MEK and ERK, and its mutation significantly promotes metastasis. However, whether BRAF could stimulate metastasis via a distinct manner is still unknown. Herein, we found that a portion of the BRAF protein localized at the plasma membrane and that the BRAFV600E mutation led to abundant formation of filopodia, which is a hallmark of invasive cancer cells. Mechanistically, BRAF physically interacts with the pseudopod formation-related protein Vasodilator-stimulated phosphoprotein (VASP), and BRAF specifically catalyzes VASP phosphorylation at Ser157. VASP depletion or disruption of Ser157 phosphorylation preferentially reduced the motility, invasion and metastasis of tumor cells harboring oncogenic BRAF or KRAS. Moreover, in clinical cancer tissues, BRAFV600E was positively correlated with the extent of invasion, and tissues with BRAFV600E expression exhibited elevated levels of VASP Ser157 phosphorylation. Our study therefor reveals a noncanonical mechanism by which oncogenic BRAF or KRAS promotes metastasis, suggests that VASP Ser157 phosphorylation might serve as a valuable therapeutic target in BRAF or KRAS mutant cancers.

Potential Oral Health Benefits of Ginseng and Its Extracts.

This review discusses the effects of ginseng and its extracts in the treatment of dental caries, periodontal diseases, endodontic diseases, oral cancers, oral mucosal diseases, and some other dental associations. In the meantime, bioavailability and safety application of ginseng products are discussed. All of the articles reviewed were from PubMed, Embase, Cochrane Library, Web of Science, China National Knowledge Infrastructure, Wanfang Data, and VIP Chinese Science and Technology Periodicals Full-Text Database through November 2022, including full-text English or non-English publications. Ginseng and its extracts were shown to have beneficial effects on oral diseases, and further studies are needed to understand the mechanisms and confirm the effects in humans.

The characteristics of HIV-1 subtype B on phylogenetic dynamic and molecular transmission network in Fuyang City, China, 2011 to 2019.

Introduction: HIV-1 subtype B, as once one of the earliest strains introduced into mainland China rapidly spread in commercial plasma donors and heterosexuals in 1990s. Here, we aim to investigate the origin and evolutionary history of HIV-1 subtype B in Fuyang city, China. Methods: We collected sequences tested from Fuyang in the east of China where higher prevalence of HIV-1 among commercial plasma donors and heterosexuals to construct a phylogenetic tree using the Markov chain Monte Carlo (MCMC) algorithm, infer molecular transmission network using TN93 model and visualize it with Cytoscape software. Results and discussion: Our results showed that >99% of subtype B sequences belonged to Thai B. The sequences from Fuyang often cluster closer to those from other its adjacent cities, which clustered together and formed a monophyletic cluster. HIV-1 B circulating in Fuyang dates back to approximately 1990. Among the 1,437 sequences, 166 clustered at a genetic distance of ≤1.2%, resulting in 73 clusters. The degree of clustering with at least one other person was 11.55%. Among the transmission clusters, 50 (80.65%) comprised two individuals. Most clusters consisted of both heterosexual transmission routes and men who have sex with men. Phylogenetic and molecular network analyses revealed a common origin with neighboring regions in mainland China, local onwards transmission after its introduction, and a limited clustering degree. However, at least two co-existing transmission routes in most transmission clusters imply a greater challenge in controlling the spread of HIV-1. Our findings highlight the value on tailoring prevention interventions by combination of molecular surveillance and epidemiology.

Association of diet quality during pregnancy with maternal glucose metabolism in Chinese women.

Overall diet quality during pregnancy has played an important role on maternal glucose metabolism. However, evidence based on the adherence to the dietary guideline is limited, especially for Asian populations. We aimed to examine the association between adherence to the Chinese dietary guideline measured by the Diet Balance Index for Pregnancy (DBI-P) and maternal glucose metabolism, including gestational diabetes mellitus (GDM) status, fasting and 2-h plasma glucose. Data were obtained from the baseline survey of the Yuexiu birth cohort. We recruited 942 pregnant women at 20-28 weeks of gestation in 2017-2018. Dietary intakes during the past month were collected using a validated semi-quantitative FFQ. The scores of DBI-P were calculated to assess dietary quality. Lower absolute values of the scores indicate higher adherence to the Chinese dietary guidelines. All participants underwent a 75 g of oral glucose tolerance test (OGTT). Multiple linear regression and logistic regression were conducted. The Benjamini-Hochberg method was used to adjust multiple comparisons across DBI-P food components. The value of high bound score indicator, reflecting excessive total food intake, was positively associated with OGTT-2h glucose levels (ß = 0·037, P = 0·029). After adjustment for multiple comparisons, the score of animal food intake was positively associated with OGTT-2 h glucose levels (ß = 0·045, P = 0·045) and risk of GDM (OR = 1·105, P = 0·030). In conclusion, excessive total food intake was associated with higher postprandial glucose in pregnant women. Lower compliance with the dietary guideline for animal food was associated with both higher postprandial glucose and increased risk of GDM during pregnancy.

Preoperative MRI features for characterization of vessels encapsulating tumor clusters and microvascular invasion in hepatocellular carcinoma.

PURPOSE: This study aimed to analyze imaging features based on preoperative dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) for the identification of vessels encapsulating tumor clusters (VETC)-microvascular invasion (MVI) in hepatocellular carcinoma (HCC), VM-HCC pattern. METHODS: Patients who underwent hepatectomy and preoperative DCE-MRI between January 2015 and March 2021 were retrospectively analyzed. Clinical and imaging features related to VM-HCC (VETC + /MVI-, VETC-/MVI +, VETC + /MVI +) and Non-VM-HCC (VETC-/MVI-) were determined by multivariable logistic regression analyses. Early and overall recurrence were determined using the Kaplan-Meier survival curve. Indicators of early and overall recurrence were identified using the Cox proportional hazard regression model. RESULTS: In total, 221 patients (177 men, 44 women; median age, 60 years; interquartile range, 52-66 years) were evaluated. The multivariable logistic regression analyses revealed fetoprotein > 400 ng/mL (odds ratio [OR] = 2.17, 95% confidence interval [CI] 1.07, 4.41, p = 0.033), intratumor vascularity (OR 2.15, 95% CI 1.07, 4.31, p = 0.031), and enhancement pattern (OR 2.71, 95% CI 1.17, 6.03, p = 0.019) as independent predictors of VM-HCC. In Kaplan-Meier survival analysis, intratumor vascularity was associated with early and overall recurrence (p < 0.05). CONCLUSION: Based on DCE-MRI, intratumor vascularity can be used to characterize VM-HCC and is of prognostic significance for recurrence in patients with HCC.

Venous gas caused by emphysematous pyelonephritis: a case report and review of literature.

BACKGROUND: Emphysematous pyelonephritis (EPN) is a potentially life-threatening disease caused by a gas-producing necrotizing bacterial infection that involves the renal parenchyma, collecting system, and/or perinephric tissue. EPN is often complicated by a previous diagnosis of diabetes mellitus, and venous air bubbles are an uncommon complication of it. We describe a 52-year-old woman who was admitted in coma, with a history of vomiting, and was found to have EPN with air bubbles in the uterine veins. We discuss the presentation, diagnosis, and pathogenesis of this uncommon but clinically significant event, and briefly review other case reports of venous gas or thrombosis caused by EPN. CASE PRESENTATION: We report the case of a 52-year-old woman with past history of type 2 diabetes mellitus, presenting with loss of consciousness after vomiting for half a day. Abdominal computed tomography scan revealed unilateral EPN with air bubbles in the uterine veins. The blood, pus, and urine cultures were positive for extended-spectrum beta-lactamase-producing Escherichia coli. The patient's condition improved well after conservative management comprising supportive measures, broad-spectrum antibiotics, percutaneous drainage therapy, and an open operation. CONCLUSIONS: Venous air bubbles are rare but fatal complication of EPN. Early diagnosis and treatment are critical to ensure good results.

Transcatheter arterial chemoembolization is safe and effective for patients with late-stage or recurrent oral carcinoma.

Objective: We reported the long-term outcomes of transcatheter chemoembolization (TACE) for patients with late-stage or recurrent oral carcinoma. Methods: This retrospective study enrolled 18 patients with late-stage or recurrent oral carcinoma between December 2015 and April 2021. The tumor-feeding artery was catheterized, and cisplatin/oxaliplatin and 5-FU/raltitrexed were infused with embolization using polyvinyl alcohol or gelatin sponge. Computed tomography was performed at about 1, 3, and 6 months after the procedure, and every 6 months after that. During the procedure and follow-up, procedure outcomes, complications, treatment efficacy, and overall survival were analyzed. Results: A total of 31 sessions of TACE were performed, with a technical success rate of 100%. Of 12 patients combined with oral hemorrhage, two patients showed rebleeding 35 and 37 days later, with a clinical efficiency of hemostasis of 88.9%. Mild complications were observed in 11 patients (61.1%). Severe complications or procedure-related deaths were not observed during or after the procedure. The objective response rate and disease control rate were 20.0% and 86.7%, 38.5% and 61.5%, and 25.0% and 50.0% at 1, 3, and 6 months later, respectively. Seventeen patients (94.4%) were followed up, with a median duration of 37.8 months (IQR 22.3-56.8). Nine patients died of tumor progression, one died of massive rebleeding, and one died of severe lung infection. The median overall survival was 23.8 months. Conclusion: TACE is a safe and effective procedure with minimal invasiveness for treating late-stage or recurrent oral carcinoma. TACE can be recommended as a palliative treatment, particularly for patients with oral hemorrhage.

Development and Validation of a Clinical-Image Model for Quantitatively Distinguishing Uncertain Lipid-Poor Adrenal Adenomas From Nonadenomas.

Background: There remains a demand for a practical method of identifying lipid-poor adrenal lesions. Purpose: To explore the predictive value of computed tomography (CT) features combined with demographic characteristics for lipid-poor adrenal adenomas and nonadenomas. Materials and Methods: We retrospectively recruited patients with lipid-poor adrenal lesions between January 2015 and August 2021 from two independent institutions as follows: Institution 1 for the training set and the internal validation set and Institution 2 for the external validation set. Two radiologists reviewed CT images for the three sets. We performed a least absolute shrinkage and selection operator (LASSO) algorithm to select variables; subsequently, multivariate analysis was used to develop a generalized linear model. The probability threshold of the model was set to 0.5 in the external validation set. We calculated the sensitivity, specificity, accuracy, and area under the receiver operating characteristic curve (AUC) for the model and radiologists. The model was validated and tested in the internal validation and external validation sets; moreover, the accuracy between the model and both radiologists were compared using the McNemar test in the external validation set. Results: In total, 253 patients (median age, 55 years [interquartile range, 47-64 years]; 135 men) with 121 lipid-poor adrenal adenomas and 132 nonadenomas were included in Institution 1, whereas another 55 patients were included in Institution 2. The multivariable analysis showed that age, male, lesion size, necrosis, unenhanced attenuation, and portal venous phase attenuation were independently associated with adrenal adenomas. The clinical-image model showed AUCs of 0.96 (95% confidence interval [CI]: 0.91, 0.98), 0.93 (95% CI: 0.84, 0.97), and 0.86 (95% CI: 0.74, 0.94) in the training set, internal validation set, and external validation set, respectively. In the external validation set, the model showed a significantly and non-significantly higher accuracy than reader 1 (84% vs. 65%, P = 0.031) and reader 2 (84% vs. 69%, P = 0.057), respectively. Conclusions: Our clinical-image model displayed good utility in differentiating lipid-poor adrenal adenomas. Further, it showed better diagnostic ability than experienced radiologists in the external validation set.

Diagnostic value of the relative enhancement ratio of the portal venous phase to unenhanced CT in the identification of lipid-poor adrenal tumors.

PURPOSE: Adrenal incidentalomas are common lesions found on abdominal imaging, most of which are lipid-rich adrenal adenomas. Imaging diagnoses differentiating lipid-poor adrenal adenomas (LPA) from non-adenomas (NA) are presently challenging to perform. The aim of the study was to investigate the diagnostic performance of the relative enhancement ratio parameter in identifying LPA from NA. METHODS: We retrospectively evaluated consecutively presenting patients with lipid-poor adrenal lesions (January 2015 to August 2021). Lesions were divided into LPA and NA (including hyperenhancing and hypoenhancing NA). Kruskal-Wallis and Bonferroni tests were used to determine the differences in feature parameters between these three groups. Receiver operating characteristic curve analysis was performed to determine the sensitivity for diagnosing LPA and NA at 95% specificity; the parameters were compared using the McNemar test. RESULTS: A total of 253 patients (mean age, 55 ± 12 years; 135 men), 121 with LPA and 132 with NA, were analyzed herein. The sensitivity (achieved at 95% specificity) of the relative enhancement ratio was higher than that of unenhanced attenuation in differentiating LPA from NA (60% vs. 52%, p = 0.064). The relative enhancement ratio yielded a higher sensitivity than unenhanced attenuation (79% vs. 59%, p < 0.001) in differentiating LPA from hypoenhancing NA, and a lower sensitivity (26% vs. 69%, p < 0.001) in differentiating LPA from hyperenhancing NA. CONCLUSION: The relative enhancement ratio showed better diagnostic performance than unenhanced attenuation in differentiating LPA from hypoenhancing NA, while simultaneously showing poor diagnostic performance in identifying LPA from all NA.

Can Radiomics Provide Additional Diagnostic Value for Identifying Adrenal Lipid-Poor Adenomas From Non-Adenomas on Unenhanced CT?

Background: It is difficult for radiologists to differentiate adrenal lipid-poor adenomas from non-adenomas; nevertheless, this differentiation is important as the clinical interventions required are different for adrenal lipid-poor adenomas and non-adenomas. Purpose: To develop an unenhanced computed tomography (CT)-based radiomics model for identifying adrenal lipid-poor adenomas to assist in clinical decision-making. Materials and methods: Patients with adrenal lesions who underwent CT between January 2015 and August 2021 were retrospectively recruited from two independent institutions. Patients from institution 1 were randomly divided into training and test sets, while those from institution 2 were used as the external validation set. The unenhanced attenuation and tumor diameter were measured to build a conventional model. Radiomics features were extracted from unenhanced CT images, and selected features were used to build a radiomics model. A nomogram model combining the conventional and radiomic features was also constructed. All the models were developed in the training set and validated in the test and external validation sets. The diagnostic performance of the models for identifying adrenal lipid-poor adenomas was compared. Results: A total of 292 patients with 141 adrenal lipid-poor adenomas and 151 non-adenomas were analyzed. Patients with adrenal lipid-poor adenomas tend to have lower unenhanced attenuation and smoother image textures. In the training set, the areas under the curve of the conventional, radiomic, and nomogram models were 0.94, 0.93, and 0.96, respectively. There was no difference in diagnostic performance between the conventional and nomogram models in all datasets (all p < 0.05). Conclusions: Our unenhanced CT-based nomogram model could effectively distinguish adrenal lipid-poor adenomas. The diagnostic power of conventional unenhanced CT imaging features may be underestimated, and further exploration is worthy.

Strategies for developing PD-1 inhibitors and future directions.

PD-L1/PD-1 signaling pathway is unarguably the hottest target for developing therapeutics against various types of cancers. With elucidation of crystal structure of PD-1/PD-L1, inhibitors targeting PD-1, PD-L1 or protein-protein interaction between them have been reported. Identification of transcription factors responsible for transcription of mRNA encoding PD-1 and PD-L1 promoted developing inhibitors to downregulate expression of either gene. Elucidation of PD-1 signaling pathway broadened strategies for drug design, for example to interfere recruitment of SHP2 by PD-1. Post-transcription modification (PTM) of phosphorylation, glycosylation, ubiquination and palmitoylation have been reported to modulate the function or homeostasis of proteins of PD-1 or PD-L1. Drugs targeting elements responsible for these PTM have been reported to enhance T cell mediated immunity. Moreover, cleverly designed protein-degrading reagents, either macromolecules or small chemicals (PROTACs) have been tried against PD-1 or PD-L1. In this review we will talk about crystal structure of PD-1/PD-L1, PD-1 signaling pathway, and physiological and pathological roles played by PD-1. Particular attention is paid on strategies for developing drugs targeting PD-1 pathways. For future directions of strategies for developing PD-1/PD-L1 inhibitors, we suggest two realistic fields: bi-functional or multi-functional small molecules; nano-material to deliver siRNAs. With recent identification of many more checkpoints in T cells through genome-wide screening and harnessing the power of nano-materials to pack multiple siRNAs, tumor microenvironment T cell specific mano-materials containing siRNAs against PD-1 and other checkpoints simultaneously could be of particular interest to industry.

No staghorn calculi and none/mild hydronephrosis may be risk factors for severe bleeding complications after percutaneous nephrolithotomy.

BACKGROUND: To explore the risk factors for severe bleeding complications after percutaneous nephrolithotomy (PCNL) according to the modified Clavien scoring system. METHODS: We retrospectively analysed 2981 patients who received percutaneous nephrolithotomies from January 2014 to December 2020. Study inclusion criteria were PCNL and postoperative mild or severe renal haemorrhage in accordance with the modified Clavien scoring system. Mild bleeding complications included Clavien 2, while severe bleeding complications were greater than Clavien 3a. It has a good prognosis and is more likely to be underestimated and ignored in retrospective studies in bleeding complications classified by Clavien 1, so no analysis about these was conducted in this study. Clinical features, medical comorbidities and perioperative characteristics were analysed. Chi-square, independent t tests, Pearson's correlation, Fisher exact tests, Mann-Whitney and multivariate logistic regression were used as appropriate. RESULTS: Of the 2981 patients 70 (2.3%), met study inclusion criteria, consisting of 51 men and 19 women, 48 patients had severe bleeding complications. The remaining 22 patients had mild bleeding. Patients with postoperative severe bleeding complications were more likely to have no or slight degree of hydronephrosis and have no staghorn calculi on univariate analysis (p < 0.05). Staghorn calculi (OR, 95% CI, p value 0.218, 0.068-0.700, 0.010) and hydronephrosis (OR, 95% CI, p value 0.271, 0.083-0.887, 0.031) were independent predictors for severe bleeding via multivariate logistic regression analysis. Other factors, such as history of PCNL, multiple kidney stones, site of puncture calyx and mean corrected intraoperative haemoglobin drop were not related to postoperative severe bleedings. CONCLUSIONS: The absence of staghorn calculi and a no or mild hydronephrosis were related to an increased risk of post-percutaneous nephrolithotomy severe bleeding complications.

Integrative molecular characterization of sarcomatoid and rhabdoid renal cell carcinoma.

Sarcomatoid and rhabdoid (S/R) renal cell carcinoma (RCC) are highly aggressive tumors with limited molecular and clinical characterization. Emerging evidence suggests immune checkpoint inhibitors (ICI) are particularly effective for these tumors, although the biological basis for this property is largely unknown. Here, we evaluate multiple clinical trial and real-world cohorts of S/R RCC to characterize their molecular features, clinical outcomes, and immunologic characteristics. We find that S/R RCC tumors harbor distinctive molecular features that may account for their aggressive behavior, including BAP1 mutations, CDKN2A deletions, and increased expression of MYC transcriptional programs. We show that these tumors are highly responsive to ICI and that they exhibit an immune-inflamed phenotype characterized by immune activation, increased cytotoxic immune infiltration, upregulation of antigen presentation machinery genes, and PD-L1 expression. Our findings build on prior work and shed light on the molecular drivers of aggressivity and responsiveness to ICI of S/R RCC.

Association between plasma irisin in pregnancy and postpartum glucose levels among Chinese women: A cohort study.

AIMS/INTRODUCTION: The association between plasma irisin and glucose levels in the general population is controversial, and few studies have longitudinally detected this correlation. We aimed to examine whether irisin in pregnancy was associated with postpartum glucose levels among Chinese women and explore the modifiable factors. MATERIALS AND METHODS: We carried out a prospective cohort study in Guangzhou, China, during 2017 and 2018, and 453 pregnant women (20-28 weeks) were enrolled. Plasma irisin levels in pregnancy were tested. At 6-8 weeks after delivery, 93 women with gestational diabetes mellitus (GDM) underwent a 75-g oral glucose tolerance test, and the other 360 women had a fasting blood glucose (FBG) test. Multivariable linear, quantile and logistic regressions were carried out. RESULTS: The mean plasma irisin in mid-pregnancy was 13.73 ng/mL. We observed a significantly negative association between mid-pregnancy irisin and postpartum FBG (ß: -0.056 ± 0.024). However, quantile regression showed the association was only significant in high percentiles of FBG levels (P50 to P95 ), and the magnitude showed an increasing trend. Higher baseline irisin was also associated with a lower risk of postpartum impaired fasting glucose (relative risk 0.563, 95% confidence interval 0.384-0.825). Furthermore, we found significant interactions between irisin and predominant breast-feeding on FBG and impaired fasting glucose (both Pinteraction  < 0.05). In women with GDM, baseline irisin was non-significantly associated with postpartum postprandial 2-h glucose levels (ß: -0.305 ± 0.160, P = 0.061). CONCLUSIONS: Plasma irisin levels in mid-pregnancy were negatively associated with FBG levels and impaired fasting glucose at 6-8 weeks postpartum among Chinese women, and stronger associations were observed in women with higher FBG values. Furthermore, breast-feeding might modify this relationship.

Abiraterone Acetate Induces CREB1 Phosphorylation and Enhances the Function of the CBP-p300 Complex, Leading to Resistance in Prostate Cancer Cells.

PURPOSE: Abiraterone acetate (AA), an inhibitor of cytochrome P450 17alpha-hydroxylase/17, 20 lyase, is an FDA-approved drug for advanced prostate cancer. However, not all patients respond to AA, and AA resistance ultimately develops in patients who initially respond. We aimed to identify AA resistance mechanisms in prostate cancer cells. EXPERIMENTAL DESIGN: We established several AA-resistant cell lines and performed a comprehensive study on mechanisms involved in AA resistance development. RNA sequencing and phospho-kinase array screenings were performed to discover that the cAMP-response element CRE binding protein 1 (CREB1) was a critical molecule in AA resistance development. RESULTS: The drug-resistant cell lines are phenotypically stable without drug selection, and exhibit permanent global gene expression changes. The phosphorylated CREB1 (pCREB1) is increased in AA-resistant cell lines and is critical in controlling global gene expression. Upregulation of pCREB1 desensitized prostate cancer cells to AA, while blocking CREB1 phosphorylation resensitized AA-resistant cells to AA. AA treatment increases intracellular cyclic AMP (cAMP) levels, induces kinases activity, and leads to the phosphorylation of CREB1, which may subsequently augment the essential role of the CBP/p300 complex in AA-resistant cells because AA-resistant cells exhibit a relatively higher sensitivity to CBP/p300 inhibitors. Further pharmacokinetics studies demonstrated that AA significantly synergizes with CBP/p300 inhibitors in limiting the growth of prostate cancer cells. CONCLUSIONS: Our studies suggest that AA treatment upregulates pCREB1, which enhances CBP/p300 activity, leading to global gene expression alterations, subsequently resulting in drug resistance development. Combining AA with therapies targeting resistance mechanisms may provide a more effective treatment strategy.

Association of Allergic Symptoms in the First 2 Years of Life With Sleep Outcomes Among Chinese Toddlers.

Background: Previous studies have linked allergic symptoms to sleep in children, but the associations might be different when considering different types of allergic symptoms or sleep outcomes. Moreover, the combined effects of multiple allergic symptoms remain unclear in early life. This study aimed to investigate the associations between multiple allergic symptoms and sleep outcomes in early life. Methods: We included 673 toddlers aged 2 years from a birth cohort in Guangzhou, China. We identified allergic symptoms (skin, eyes and nose, gastrointestinal tract, mouth and lips, and wheeze) within 2 years via standard questionnaires. Sleep outcomes including sleep duration and quality over the past month were assessed based on the Chinese version of the Brief Infant Sleep Questionnaire. Associations between allergic symptoms and sleep outcomes were examined using multivariable linear regression and logistic regression. Results: Compared to children without allergic symptoms, children with allergic nasal and ocular symptoms had higher odds of frequent nighttime awakenings (OR = 1.41; 95% CI: 1.03, 1.93) and irregular sleep (OR = 1.45, 95% CI: 1.05, 2.00); children with allergic gastrointestinal symptoms slept 0.28 h less during nighttime (95% CI: -0.48, -0.07) and 0.25 h less per day (95% CI: -0.43, -0.08), and had 59% higher odds of irregular sleep (95% CI: 1.24, 2.04). We also found significant association of multiple allergic symptoms with shortened nighttime sleep duration and increased irregular sleep. Whereas, allergic skin, mouth and lips, and wheeze symptoms were not significantly associated with sleep outcomes. Conclusion: Allergic symptoms within 2 years of age were adversely associated with sleep outcomes, which highlight the importance of early screening of allergic symptoms in toddlers in order to improve their sleep outcomes.