A nomogram based on nutritional and inflammatory parameters to predict DMFS and identify beneficiaries of adjuvant chemotherapy in IVA-stage nasopharyngeal carcinoma.

OBJECTIVE: This study aims to develop a nomogram integrating inflammation (NLR), Prognostic Nutritional Index (PNI), and EBV DNA (tumor burden) to achieve personalized treatment and prediction for stage IVA NPC. Furthermore, it endeavors to pinpoint specific subgroups that may derive significant benefits from S-1 adjuvant chemotherapy. METHODS: A total of 834 patients diagnosed with stage IVA NPC were enrolled in this study and randomly allocated into training and validation cohorts. Multivariate Cox analyses were conducted to identify independent prognostic factors for constructing the nomogram. The predictive and clinical utility of the nomogram was assessed through measures including the AUC, calibration curve, DCA, and C-indexes. IPTW was employed to balance baseline characteristics across the population. Kaplan-Meier analysis and log-rank tests were utilized to evaluate the prognostic value. RESULTS: In our study, we examined the clinical features of 557 individuals from the training cohort and 277 from the validation cohort. The median follow-up period was 50.1 and 49.7 months, respectively. For the overall cohort, the median follow-up duration was 53.8 months. The training and validation sets showed 3-year OS rates of 87.7% and 82.5%, respectively. Meanwhile, the 3-year DMFS rates were 95.9% and 84.3%, respectively. We created a nomogram that combined PNI, NRI, and EBV DNA, resulting in high prediction accuracy. Risk stratification demonstrated substantial variations in DMFS and OS between the high and low risk groups. Patients in the high-risk group benefited significantly from the IC + CCRT + S-1 treatment. In contrast, IC + CCRT demonstrated non-inferior 3-year DMFS and OS compared to IC + CCRT + S-1 in the low-risk population, indicating the possibility of reducing treatment intensity. CONCLUSIONS: In conclusion, our nomogram integrating NLR, PNI, and EBV DNA offers precise prognostication for stage IVA NPC. S-1 adjuvant chemotherapy provides notable benefits for high-risk patients, while treatment intensity reduction may be feasible for low-risk individuals.

Comorbidity profiling identifies potential subtype of elderly patients with nasopharyngeal carcinoma.

BACKGROUND: Few studies have assessed the comprehensive associations among comorbid diseases in elderly patients with nasopharyngeal carcinoma (NPC). This study sought to identify potential comorbidity patterns and explore the relationship of comorbidity patterns with the mortality risk in elderly patients with NPC. METHODS: A total of 452 elderly patients with NPC were enrolled in the study. The network analysis and latent class analysis were applied to mine comorbidity patterns. Propensity score matching was used for adjusting confounders. A restricted cubic spline model was used to analyze the nonlinear association between age and the risk of all-cause mortality. RESULTS: We identified 2 comorbidity patterns, metabolic disease-related comorbidity (MDRC) and organ disease-related comorbidity (ODRC) in elderly patients with NPC. Patients in MDRC showed a significantly higher risk of all-cause mortality (71.41% vs 87.97%, HR 1.819 [95% CI, 1.106-2.994], P = .031) and locoregional relapse (68.73% vs 80.88%, HR 1.689 [95% CI, 1.055-2.704], P = .042). Moreover, in patients with MDRC pattern, we observed an intriguing inverted S-shaped relationship between age and all-cause mortality among patients aged 68 years and older. The risk of mortality up perpetually with age increasing in ODRC group, specifically within the age range of 68-77 years (HR 4.371, 1.958-9.757). CONCLUSION: Our study shed light on the potential comorbidity patterns in elderly patients with NPC, thereby providing valuable insights into the development of comprehensive health management strategies for this specific population.

Extracorporeal Versus Conventional Cardiopulmonary Resuscitation for In-Hospital Cardiac Arrest: A Propensity Score Matching Cohort Study.

OBJECTIVE: Comparing the effects of extracorporeal cardiopulmonary resuscitation (ECPR) and conventional cardiopulmonary resuscitation (CCPR) on outcomes in patients with in-hospital cardiac arrest (IHCA) in China. The benefits of ECPR over CCPR in patients with IHCA remain controversial. DESIGN: This article analyzed data from the BASeline Investigation of In-hospital Cardiac Arrest (BASIC-IHCA) study, which consecutively enrolled patients with IHCA from July 1, 2019, to December 31, 2020. Patients who received ECPR were selected as the case group and matched with patients who received CCPR as the control group by propensity score at a ratio of 1:4. A parallel questionnaire survey of participating hospitals was conducted, to collect data on ECPR cases from January 1, 2021 to November 30, 2021. The primary outcome was survival to discharge or 30-day survival. SETTING: We included 39 hospitals across 31 provinces in China. PATIENTS: Patients receiving cardiopulmonary resuscitation and without contraindications to ECPR were selected from the BASIC-IHCA database. Patients older than 75 years, not witnessed, or with cardiopulmonary resuscitation duration less than 10 min were excluded. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A total of 4853 patients met the inclusion criteria before matching, with 34 undergoing ECPR (median age, 56.5 yr; 67.65% male) and 4819 underwent CCPR (median age, 59 yr; 64.52% male). There were 132 patients receiving CCPR and 33 patients receiving ECPR who were eventually matched. The ECPR group had significantly higher survival rates at discharge or 30-day survival (21.21% vs. 7.58%, p = 0.048). The ECPR group had significantly lower mortality rates (hazard ratio 0.57; 95% CI, 0.38-0.91) than the CCPR group at discharge or 30 days. Besides the BASIC-IHCA study, the volume of ECPR implementations and the survival rate of patients with ECPR (29.4% vs. 10.4%. p = 0.004) in participating hospitals significantly improved. CONCLUSIONS: ECPR may be beneficial compared with CCPR for patient survival after IHCA and should be considered for eligible patients with IHCA.

Single Cell Sequencing Technology and Its Application in Alzheimer's Disease.

Alzheimer's disease (AD) involves degeneration of cells in the brain. Due to insidious onset and slow progression, AD is often not diagnosed until it gets progressed to a more severe stage. The diagnosis and treatment of AD has been a challenge. In recent years, high-throughput sequencing technologies have exhibited advantages in exploring the pathogenesis of diseases. However, the types of cells of the central nervous system are complex and traditional bulk sequencing cannot reflect their heterogeneity. Single-cell sequencing technology enables study at the individual cell level and has an irreplaceable advantage in the study of complex diseases. In recent years, this field has expanded rapidly and several types of single-cell sequencing technologies have emerged, including transcriptomics, epigenomics, genomics and proteomics. This review article provides an overview of these single-cell sequencing technologies and their application in AD.

TREATMENT OF COMATOSE SURVIVORS OF IN-HOSPITAL CARDIAC ARREST WITH EXTENDED ENDOVASCULAR COOLING METHOD FOR 72 H: A PROPENSITY SCORE-MATCHED ANALYSIS.

ABSTRACT: Aims: Targeted temperature management is recommended for at least 24 h in comatose survivors of in-hospital cardiac arrest (IHCA) after the return of spontaneous circulation; however, whether an extension for 72 h leads to better neurological outcomes is uncertain. Methods: We included data from the Qilu Hospital of Shandong University between July 20, 2019, and June 30, 2022. Unconscious patients who had return of spontaneous circulation lasting >20 consecutive min and received endovascular cooling (72 h) or normothermia treatment were compared in terms of survival-to-discharge and favorable neurological survival. Propensity score matching was used to formulate balanced 1:3 matched patients. Results: In total, 2,084 patients were included. Sixteen patients received extended endovascular cooling and 48 matched controls received normothermia therapy. Compared with the normothermia group, patients who received prolonged endovascular cooling had a higher survival-to-discharge rate. However, good neurological outcomes did not differ significantly. Before matching, Cox regression analysis, using mortality as the event, showed that extended endovascular cooling independently affected the survival of IHCA patients. Conclusions: Among comatose patients who had been resuscitated from IHCA, the use of endovascular cooling for 72 h might confer a benefit on survival-to-discharge.

Effects of xanthan gum, konjac glucomannan, and arabinogalactan on the in vitro digestion and fermentation characteristics of biscuits.

Background: Diabetes and its complications have a significant economic impact on individuals and their families. A diet with a low glycemic index (GI) and high fiber content is considered to be associated with the control of blood glucose. Scope and approach: This study explored the effect of polysaccharides, i.e., xanthan gum (BXG), konjac glucomannan (BKG), and arabinogalactan (BAG), on the digestive and prebiotic characteristics of biscuits using a simulated digestion and fermentation model in vitro. Also, the rheological property and structural properties of the polysaccharides were measured to clarify their structure-activity relationships. Key findings and conclusions: During simulated gastrointestinal digestion, the results showed that three types of biscuits containing polysaccharides were low GI foods (estimated GI < 55), in which BAG had the lowest estimated GI value. During in vitro fermentation with diabetic or healthy subjects' fecal microbiota, the three types of biscuits containing polysaccharides (after digestion) decreased the fermentation pH, increased the level of short-chain fatty acids, and modulated the microbiota composition over time. Among the three types of biscuits, BAG increased the abundance of Bifidobacterium and Lactobacillus during fermentation in diabetic and healthy subjects' fecal microbiota. These results showed that the addition of a lower-viscosity polysaccharide (arabinogalactan) may be more beneficial for the blood glucose control of biscuits.

Prognostic model on overall survival in elderly nasopharyngeal carcinoma patients: a recursive partitioning analysis identifying pre-treatment risk stratification.

BACKGROUND: We aimed to evaluate the optimal management for elderly patients with nasopharyngeal carcinoma (NPC) with intensity-modulated radiotherapy (IMRT). METHODS: A total of 283 elderly patients with NPC diagnosed from 2015 to 2019 were enrolled in the study. Overall survival (OS) was the primary endpoint. Univariate and multivariate Cox regression analyses were preformed to identify potential prognostic factors. The recursive partitioning analysis (RPA) was used for risk stratification. Kaplan-Meier survival curves were applied to evaluate the survival endpoints, and log-rank test was utilized to assess differences between groups. The prognostic index (PI) was constructed to further predict patients' prognosis displayed by nomogram model. The area under the receiver operating characteristic (ROC) curves (AUC) and the calibration curves were applied to assess the effectiveness of the model. RESULTS: Based on RPA-based risk stratification, we demonstrated that elderly NPC patients who were treated with IC followed by RT had similar OS as those with induction chemotherapy (IC) combined with concurrent chemoradiotherapy (CCRT) in the middle- (stage I-III and pre-treatment EBV > 1840 copies/ml) and high-risk groups (stage IVA). IMRT alone may be the optimal treatment option for the low-risk group (stage I-III with pre-treatment EBV ≤ 1840 copies/ml). We established an integrated PI which was indicted with stronger prognostic power than each of the factors alone for elderly NPC patients (The AUC of PI was 0.75, 0.80, and 0.82 for 1-, 3-, 5-year prediction of OS, respectively). CONCLUSION: We present a robust model for clinical stratification which could guide individual therapy for elderly NPC patients.

Synchronous Medical Image Augmentation framework for deep learning-based image segmentation.

Various deep learning (DL) models are widely applied in medical image analysis, and their performance depends on the scale and diversity of available training data. However, medical images often suffer from difficulty in data acquisition, imbalance in sample categories, and high cost of labeling. In addition, most image augmentation approaches mainly focus on image synthesis only for classification tasks, and rarely consider the synthetic image-label pairs for image segmentation tasks. In this paper, we focus on the medical image augmentation for DL-based image segmentation and the synchronization between augmented image samples and their labels. We design a Synchronous Medical Image Augmentation (SMIA) framework, which includes two modules based on stochastic transformation and synthesis, and provides diverse and annotated training sets for DL models. In the transform-based SMIA module, for each medical image sample and its tissue segments, a subset of SMIA factors with a random number of factors and stochastic parameter values are selected to simultaneously generate augmented samples and the paired tissue segments. In the synthesis-based SMIA module, we randomly replace the original tissues with the augmented tissues using an equivalent replacement method to synthesize new medical images, which can well maintain the original medical implications. DL-based image segmentation experiments on bone marrow smear and dermoscopic images demonstrate that the proposed SMIA framework can generate category-balanced and diverse training data, and have a positive impact on the performance of the models.

Upregulation of PNCK Promotes Metastasis and Angiogenesis via Activating NF-κB/VEGF Pathway in Nasopharyngeal Carcinoma.

Background: Distant metastasis is the major cause of treatment failure in patients with nasopharyngeal carcinoma (NPC). Thus, the identification of the molecular mechanisms and the development of novel therapeutic strategies are important. Previous studies suggest that PNCK promotes tumor growth by suppressing PI3K/AKT/mTOR signaling in NPC. However, the underlying regulatory mechanism of PNCK for NPC invasion and metastasis remains unclear. Methods: The PNCK expression level was evaluated in nonmetastatic and metastatic NPC specimens by mRNA sequencing and immunohistochemistry. In vitro migration and invasion and in vivo nude mouse metastasis model and zebrafish model were used to evaluate the effects of PNCK ectopic expression on the metastatic ability of NPC cells. Gene set enrichment and western blot analyses were used to investigate the PNCK downstream signaling pathway. Results: Human metastatic NPC samples showed elevated PNCK expression at both mRNA and protein levels. Upregulated PNCK promoted in vitro NPC cell migration, invasion, and the formation of lung metastases; the vascular-labeled fluorescence signal increased in the in vivo zebrafish model. Mechanistically, pathway analysis showed that the upregulation of PNCK may promote cell metastasis by activating the NF-κB/VEGF signaling pathway. Conclusions: These findings revealed the specific critical role of PNCK in promoting NPC metastasis and angiogenesis, which suggested that PNCK may have implications as a potential therapeutic target for individualized NPC treatment.

Identification of a ferroptosis-associated gene signature and the related therapeutic targets in head and neck squamous carcinoma.

BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) has a poor prognosis due to its high rates of recurrence and metastasis. Herein, we designed and validated an individualized ferroptosis-associated gene signature (FGS) and further probed the potential survival mechanisms along with therapeutic targets for HNSCC. METHODS: The FGS risk score was constructed using stepwise regression analysis and validated in the GSE41613 cohort. Characterization of the tumor microenvironment (TME) in patients with HNSCC, involving immune cells and immunomodulatory genes, was performed to investigate the survival mechanisms and therapeutic targets associated with FGS. To validate the role of FGS in TME, multiplex fluorescent immunohistochemistry (mfIHC) was performed on tissue sections from 55 patients with oral squamous carcinoma. RESULTS: The risk score obtained from FGS showed good predictive power as an independent predictor of overall survival. From the tumor immune dysfunction and exclusion (TIDE) prediction, it was found that patients at low risk may benefit from immunotherapy. Furthermore, FGS was significantly associated with CD276, which was highly expressed in fibroblasts that enriched in angiogenesis and epithelial-mesenchymal transition pathways at a single-cell resolution, suggesting CD276 may play a critical mediator of the immunosuppressive microenvironment. Lastly, we identified ATG5 as a critical gene in FGS. And the immune-bioinformatics analysis combined with experimental validation showed a negative correlation between ATG5 expression and CD8 + T cells. CONCLUSION: The FGS model provides a novel and effective method to predict the prognosis of patients with HNSCC and their survival can be prolonged through TME-related therapeutic targets.

Comparison of Safety and Efficacy Between Clopidogrel and Ticagrelor in Elderly Patients With Acute Coronary Syndrome: A Systematic Review and Meta-Analysis.

Background: Dual antiplatelet therapy combining aspirin with a P2Y12 adenosine diphosphate receptor inhibitor is a therapeutic mainstay for acute coronary syndrome (ACS). However, the optimal choice of P2Y12 adenosine diphosphate receptor inhibitor in elderly (aged ≥65 years) patients remains controversial. We conducted a meta-analysis to compare the efficacy and safety of ticagrelor and clopidogrel in elderly patients with ACS. Methods: We comprehensively searched in Web of Science, EMBASE, PubMed, and Cochrane databases through 29th March, 2021 for eligible randomized controlled trials (RCTs) comparing the efficacy and safety of ticagrelor or clopidogrel plus aspirin in elderly patients with ACS. Four studies were included in the final analysis. A fixed effects model or random effects model was applied to analyze risk ratios (RRs) and hazard ratios (HRs) across studies, and I2 to assess heterogeneity. Results: A total number of 4429 elderly patients with ACS were included in this analysis, of whom 2170 (49.0%) patients received aspirin plus ticagrelor and 2259 (51.0%) received aspirin plus clopidogrel. The ticagrelor group showed a significant advantage over the clopidogrel group concerning all-cause mortality (HR 0.78, 95% CI 0.63-0.96, I2 = 0%; RR 0.79, 95% CI 0.66-0.95, I2 = 0%) and cardiovascular death (HR 0.71, 95% CI 0.56-0.91, I2 = 0%; RR 0.76, 95% CI 0.62-0.94, I2 = 5%) but owned a higher risk of PLATO major or minor bleeding (HR 1.46, 95% CI 1.13-1.89, I2 = 0%; RR 1.40, 95% CI 1.11-1.76, I2 = 0%). Both the groups showed no significant difference regarding major adverse cardiovascular events (MACEs) (HR 1.06, 95% CI 0.68-1.65, I2 = 77%; RR 1.04, 95% CI 0.69-1.58, I2 = 77%). Conclusion: For elderly ACS patients, aspirin plus ticagrelor reduces cardiovascular death and all-cause mortality but increases the risk of bleeding. Herein, aspirin plus ticagrelor may extend lifetime for elderly ACS patients compared with aspirin plus clopidogrel. The optimal DAPT for elderly ACS patients may be a valuable direction for future research studies.

A Novel Prognostic Signature Based on Metabolism-Related Genes to Predict Survival and Guide Personalized Treatment for Head and Neck Squamous Carcinoma.

Metabolic reprogramming contributes to patient prognosis. Here, we aimed to reveal the comprehensive landscape in metabolism of head and neck squamous carcinoma (HNSCC), and establish a novel metabolism-related prognostic model to explore the clinical potential and predictive value on therapeutic response. We screened 4752 metabolism-related genes (MRGs) and then identified differentially expressed MRGs in HNSCC. A novel 10-MRGs risk model for prognosis was established by the univariate Cox regression analysis and the least absolute shrinkage and selection operator (Lasso) regression analysis, and then verified in both internal and external validation cohort. Kaplan-Meier analysis was employed to explore its prognostic power on the response of conventional therapy. The immune cell infiltration was also evaluated and we used tumor immune dysfunction and exclusion (TIDE) algorithm to estimate potential response of immunotherapy in different risk groups. Nomogram model was constructed to further predict patients' prognoses. We found the MRGs-related prognostic model showed good prediction performance. Survival analysis indicated that patients suffered obviously poorer survival outcomes in high-risk group (p < 0.001). The metabolism-related signature was further confirmed to be the independent prognostic value of HNSCC (HR = 6.387, 95% CI = 3.281-12.432, p < 0.001), the efficacy of predictive model was also verified by internal and external validation cohorts. We observed that HNSCC patients would benefit from the application of chemotherapy in the low-risk group (p = 0.029). Immunotherapy may be effective for HNSCC patients with high risk score (p < 0.01). Furthermore, we established a predictive nomogram model for clinical application with high performance. Our study constructed and validated a promising 10-MRGs signature for monitoring outcome, which may provide potential indicators for metabolic therapy and therapeutic response prediction in HNSCC.

Effect of baffle structure on flow field characteristics of orbitally shaken bioreactor.

Disposable orbitally shaken bioreactors have been widely used for mammalian cell culture in suspension. Three kinds of baffle structures: vertical baffle, inclined baffle and horizontal baffle were designed in this work. The flow fields of the shaking bioreactor with different baffle structures were simulated, and the turbulence, dissolved oxygen and shear strain rate of the bioreactor were analyzed. The results showed that the quasi-steady-state flow patterns of the unbaffled shaking bioreactors were broken for the bioreactors with the strengthening effects of baffles. The mixing and the oxygen volumetric mass transfer coefficient (kLa) (simulated results) were improved significantly, and the shear strain rates were also increased greatly for the baffle bioreactors. The shear strain rates of the baffle bioreactors were mainly in the range of 0-20 s-1, and they were still low enough for CHO cell cultures.

Characterization of Hypoxia Signature to Evaluate the Tumor Immune Microenvironment and Predict Prognosis in Glioma Groups.

Glioma groups, including lower-grade glioma (LGG) and glioblastoma multiforme (GBM), are the most common primary brain tumor. Malignant gliomas, especially glioblastomas, are associated with a dismal prognosis. Hypoxia is a driver of the malignant phenotype in glioma groups; it triggers a cascade of immunosuppressive processes and malignant cellular responses (tumor progression, anti-apoptosis, and resistance to chemoradiotherapy), which result in disease progression and poor prognosis. However, approaches to determine the extent of hypoxia in the tumor microenvironment are still unclear. Here, we downloaded 575 LGG patients and 354 GBM patients from Chinese Glioma Genome Atlas (GGGA), and 530 LGG patients and 167 GBM patients from The Cancer Genome Atlas (TCGA) with RNA sequence and clinicopathological data. We developed a hypoxia risk model to reflect the immune microenvironment in glioma and predict prognosis. High hypoxia risk score was associated with poor prognosis and indicated an immunosuppressive microenvironment. Hypoxia signature significantly correlated with clinical and molecular features and could serve as an independent prognostic factor for glioma patients. Moreover, Gene Set Enrichment Analysis showed that gene sets associated with the high-risk group were involved in carcinogenesis and immunosuppression signaling. In conclusion, we developed and validated a hypoxia risk model, which served as an independent prognostic indicator and reflected overall immune response intensity in the glioma microenvironment.

Study on the chemodrug-induced effect in nasopharyngeal carcinoma cells using laser tweezer Raman spectroscopy.

To explore the effect in nasopharyngeal carcinoma (NPC) cells after treatment with chemodrugs, Raman profiles were characterized by laser tweezer Raman spectroscopy. Two NPC cell lines (CNE2 and C666-1) were treated with gemcitabine, cisplatin, and paclitaxel, respectively. The high-quality Raman spectra of cells without or with treatments were recorded at the single-cell level with label-free laser tweezers Raman spectroscopy (LTRS) and analyzed for the differences of alterations of Raman profiles. Tentative assignments of Raman peaks indicated that the cellular specific biomolecular changes associated with drug treatment include changes in protein structure (e.g. 1655 cm-1), changes in DNA/RNA content and structure (e.g. 830 cm-1), destruction of DNA/RNA base pairs (e.g. 785 cm-1), and reduction in lipids (e.g. 970 cm-1). Besides, both principal components analysis (PCA) combined with linear discriminant analysis (LDA) and the classification and regression trees (CRT) algorithms were employed to further analyze and classify the spectral data between control group and treated group, with the best discriminant accuracy of 96.7% and 90.0% for CNE2 and C666-1 group treated with paclitaxel, respectively. This exploratory work demonstrated that LTRS technology combined with multivariate statistical analysis has promising potential to be a novel analytical strategy at the single-cell level for the evaluation of NPC-related chemotherapeutic drugs.

Raman profile alterations of irradiated human nasopharyngeal cancer cells detected with laser tweezer Raman spectroscopy.

Radiotherapy has been widely used for nasopharyngeal carcinoma (NPC) treatment, which causes DNA damage and alterations of macromolecules of cancer cells. However, the Raman profile alterations of irradiated NPC cells remain unclear. In the present study, we used laser tweezers Raman spectroscopy (LTRS) to monitor internal structural changes and chemical modifications in NPC cells after exposure at a clinical dose (2.3 Gy) to X-ray irradiation (IR) at a single-cell level. Two types of NPC cell lines, CNE2 (EBV-negative cell line) and C666-1 (EBV-positive cell line), were used. The Raman spectra of cells before and after radiation treatment were recorded by LTRS. The analysis of spectral differences indicated that the IR caused Raman profile alterations of intracellular proteins, DNA base and lipids. Moreover, by using the multivariate statistical analysis including principal component analysis (PCA) and linear discriminant analysis (LDA) algorithm, an accuracy of 90.0% for classification between CNE2 cells before and after IR could be achieved, which was 10% better than that of C666-1 cells. The results demonstrated that CNE2 cells were more sensitive to IR in comparison to C666-1 cells, providing useful information for creating a treatment strategy in clinical practice. This exploratory study suggested that LTRS combined with multivariate statistical analysis would be a novel and effective tool for evaluating the radiotherapeutic effect on tumor cells, and for detection of the corresponding alterations at the molecular level.

Embryonic cholesterol esterification is regulated by a cyclic AMP-dependent pathway in yolk sac membrane-derived endodermal epithelial cells.

During avian embryonic development, endodermal epithelial cells (EECs) absorb yolk through the yolk sac membrane. Sterol O-acyltransferase (SOAT) is important for esterification and yolk lipid utilization during development. Because the major enzyme for yolk sac membrane cholesteryl ester synthesis is SOAT1, we cloned the avian SOAT1 promoter and elucidated the cellular functions of SOAT1. Treatments with either glucagon, isobutylmethylxanthine (IBMX), an adenylate cyclase activator (forskolin), a cAMP analog (dibutyryl-cAMP), or a low glucose concentration all increased SOAT1 mRNA accumulation in EECs from Japanese quail, suggesting that SOAT1 is regulated by nutrients and hormones through a cAMP-dependent pathway. Activity of protein kinase A (PKA) was increased by IBMX, whereas co-treatment with the PKA inhibitor, H89 negated the increase in PKA activity. Cyclic AMP-induced EECs had greater cholesterol esterification than untreated EECs. By promoter deletion and point-mutation, the cAMP-response element (-349 to -341 bp) was identified as critical in mediating transcription of SOAT1. In conclusion, expression of SOAT1 was regulated by a cAMP-dependent pathway and factors that increase PKA will increase SOAT1 to improve the utilization of lipids in the EECs and potentially modify embryonic growth.

Unidimensional measurement may be superior to assess primary tumor response after neoadjuvant chemotherapy for nasopharyngeal carcinoma.

Application of current response evaluation criteria in solid tumors (RECIST 1.1) for assessment of irregularly shaped nasopharyngeal carcinoma (NPC) is a gray area with much ambiguity. Our aim was to compare unidimensional measurements (UDM) and bidimensional measurements (BDM) on magnetic resonance images in alternative planes for measurement of tumor response after neoadjuvant chemotherapy (NACT) in patients with locally advanced NPC. 59 patients with untreated non-metastatic NPC were prospectively enrolled. The size or change in size of the primary tumor and retropharyngeal nodes was assessed by UDM and BDM on axial and coronal planes before and after 2 cycles of NACT. Tumor volume was considered as the reference standard. Correlation between volume and diameter was analyzed using a general linear model. The degree of agreement and discordance of response classification based on different measures were evaluated with κ statistic and McNemar's test, respectively. Both axial UDM (RECIST 1.1) and axial BDM (WHO) showed a significant association with volumetric standard. However, the agreement of axial UDM with VM was better than that of axial BDM (κ value: 0.514 to 0.372). In addition, when increasing coronal planes to evaluate tumor response with UDM and BDM, an inferior agreement between coronal BDM and VM was still observed. Notably, coronal UDM showed the best consistency with volume (κ = 0.585). Hence, axial UDM showed better correlation with volumetric measurements than axial BDM. Since coronal UDM showed high correlation to VM, we suggest further research to assess its use for response assessment of NPC after NACT.

Alleviation of Carbon-Tetrachloride-Induced Liver Injury and Fibrosis by Betaine Supplementation in Chickens.

Betaine is a food component with well-reported hepatoprotection effects. However, the effects and mechanisms of betaine on liver fibrosis development are still insufficient. Because metabolic functions of chicken and human liver is similar, we established a chicken model with carbon Tetrachloride- (CCl4-) induced fibrosis for studying antifibrotic effect of betaine in vivo and in vitro. Two-week-old male chicks were supplemented with betaine (1%, w/v) in drinking water for 2 weeks prior to the initiation of CCl4 treatment (i.p.) until sacrifice. Primary chicken hepatocytes were treated with CCl4 and betaine to mimic the in vivo supplementation. The supplementation of betaine significantly alleviated liver fibrosis development along with the inhibition of lipid peroxidation, hepatic inflammation cytokine, and transforming growth factor-ß1 expression levels. These inhibitive effects were also accompanied with the attenuation of hepatic stellate cell activation. Furthermore, our in vitro studies confirmed that betaine provides antioxidant capacity for attenuating the hepatocyte necrosis by CCl4. Altogether, our results highlight the antioxidant ability of betaine, which alleviates CCl4-induced fibrogenesis process along with the suppression of hepatic stellate cells activation. Since betaine is a natural compound without toxicity, we suggest betaine can be used as a potent nutritional or therapeutic factor for reducing liver fibrosis.