Therapeutic mechanism of Cornus Officinalis Fruit Coreon on ALI by AKT/Nrf2 pathway and gut microbiota.

BACKGROUND: Acute liver injury (ALI) often precipitates severe liver function impairment and is associated with high mortality rates. Traditional Chinese Medicine (TCM) has demonstrated efficacy in mitigating hepatic damage by exhibiting anti-inflammatory effects, enhancing antioxidant activity, and modulating gut microbiota (GM). Numerous studies have identified similar or identical bioactive compounds within the Cornus Officinalis Fruit Coreon(COFO) and its flesh. Notably, Cornus Officinalis has been shown to possess potent hepatoprotective properties. However, studies on the pharmacological effects and mechanism of action of COFO for hepatoprotection have received little attention. PURPOSE: To elucidate the mechanisms underlying the COFO effect in ALI by integrating GM gene sequencing, quantifying Short-Chain Fatty Acids (SCFAs), and examining relevant signaling pathways. MATERIALS AND METHODS: A rat model for carbon tetrachloride (CCl4)-induced ALI was established, and the best liver protective components of COFO were selected by pathological observation and biochemical determination. The therapeutic efficacy of COFO in mitigating liver injury was elucidated through an integrated approach that included network pharmacology, biochemical indexes, 16S rDNA sequencing analyses, short-chain fatty acids, Western blotting analysis of protein levels, and immunohistochemical evaluations. RESULTS: Pharmacological evaluation established that the n-butanol fraction (CNBP) provided optimal hepatoprotective effects. Firstly, the chemical constituents of CNBP were characterized, and its principal anti-ALI targets, such as ALI, AKT1, TNF, and IL-6, were identified through network pharmacology analysis. Secondly, experimental validation revealed that CNBP may enhance the genetic diversity of the GM, augmenting the diversity of the microbial community, increasing the levels of three SCFAs, and activating key proteins in the AKT/Nrf2 signaling pathway (AKT1, TNF-α, IL-6, NF-κB p65, Nrf2, and HO-1). Consequently, CNBP exhibited hepatoprotective effects, with antioxidative and anti-inflammatory properties. CONCLUSION: CNBP may mitigate GM-induced disturbances, augment the levels of three SCFAs, activate the AKT/Nrf2 signaling pathway, and exhibit antioxidant and anti-inflammatory effects, thereby conferring hepatoprotective benefits.

Nomogram Incorporating Contrast-Enhanced Ultrasonography Predicting Time to the Development of Castration-Resistant Prostate Cancer.

BACKGROUND: It is valuable to predict the time to the development of castration-resistant prostate cancer (CRPC) in patients with advanced prostate cancer (PCa). This study aimed to build and validate a nomogram incorporating the clinicopathologic characteristics and the parameters of contrast-enhanced ultrasonography (CEUS) to predict the time to CRPC after androgen deprivation therapy (ADT). METHODS: Patients with PCa were divided into the training (n = 183) and validation cohorts (n = 37) for nomogram construction and validation. The clinicopathologic characteristics and CEUS parameters were analyzed to determine the independent prognosis factors and serve as the basis of the nomogram to estimate the risk of 1-, 2-, and 3-year progress to CRPC. RESULTS: T stage, distant metastasis, Gleason score, area under the curve (AUC), prostate-specific antigen (PSA) nadir, and time to PSA nadir were the independent predictors of CRPC (all P < 0.05). Three nomograms were built to predict the time to CRPC. Owing to the inclusion of CEUS parameter, the discrimination of the established nomogram (C-index: 0.825 and 0.797 for training and validation datasets) was improved compared with the traditional prediction model (C-index: 0.825 and 0.797), and when it excluded posttreatment PSA, it still obtained an acceptable discrimination (C-index: 0.825 and 0.797). CONCLUSIONS: The established nomogram including regular prognostic indicators and CEUS obtained an improved accuracy for the prediction of the time to CRPC. It was also applicable for early prediction of CRPC when it excluded posttreatment PSA, which might be helpful for individualized diagnosis and treatment.

Nomogram Prediction of Short-Term Outcome After Intracerebral Hemorrhage.

BACKGROUND: The early symptoms of patients with elevated intracranial pressure (ICP) after intracerebral hemorrhage (ICH) are easily overlooked, which will result in missing the optimal opportunity for clinical intervention. However, it is difficult for ICH patients admitted to the neurology department to receive invasive ICP monitoring, although it is crucial for the early identification of neurologic deterioration (ND). OBJECTIVE: The aim of this study is to investigate the association between the changes of transcranial Doppler (TCD) variables and ND after onset and establish a nomogram for predicting the short-term outcome of ICH. METHODS: A total of 297 patients were recruited and their clinical characteristics and the changes of TCD variables were recorded. The independent prognostic factors for the ND after onset in the ICH patients were screened from multivariate Logistic regression analysis, which were served as inputs for the nomogram construction. Discrimination and calibration validations were performed to assess the performance of the nomogram [concordance index (C-index) for discrimination and Hosmer-Lemeshow (HL) test for calibration] and the decision curve analysis was applied to assess the clinical suitability. RESULTS: ΔaPI [defined as the change of pulsatility index (PI) between the 1st and 3rd day after onset for affected hemisphere] was independently associated with the ND after onset. Moreover, hematoma volume, presence of intraventricular hemorrhage, and Glasgow coma scale were also the independent prognostic factors of ND. The developed nomogram incorporating ΔaPI showed good discrimination (C-index: 0.916 after 1000 bootstrapping) and calibration (P=0.412, HL test) and yielded net benefits. CONCLUSION: The nomogram incorporating ΔaPI might be useful in predicting the risk of ND within 14 days after onset, which might help identify patients in the neurology department in need of further care.

Association of body composition with predicted hip bone strength among Chinese postmenopausal women: a longitudinal study.

Body composition and bone strength are closely associated. How lean mass (LM) and fat mass (FM) contribute to bone strength remains ambiguous. We investigated the associations of total body LM and FM with changes in predicted hip bone strength over a period of 3 years in 1,743 postmenopausal Chinese women from the communities of Guangzhou, China. The body compositions of the women were obtained with dual-energy X-ray absorptiometry. We used the hip structure analysis program to obtain the bone parameters at the femoral neck region, including the bone mineral density (BMD), cross-sectional area (CSA), cortical thickness (CT), section modulus (SM) and buckling ratio (BR). We found the FM and LM were positive predictors for hip bone strength (ß > 0, P < 0.05). The LM had a larger contribution to the BMD, CSA, CT, SM and/or their annual percent changes (ßLM > ßFM), while the contribution of FM to the BR and its annual percent change was higher than LM (|ßFM| > |ßLM|). Further analysis found that the associations of FM and LM with bone parameters were stronger in the underweight and normal weight participants (|ßBMI1| > |ßBMI2|). Overall, FM and LM had positive but differential effects on predicted hip bone strength, with a higher impact in the thinner participants.

Ultrasonography is valuable in evaluation of papillary thyroid microcarcinoma based on 5 mm tumor size.

INTRODUCTION: Fine-needle aspiration was once done in suspected malignant thyroid nodules more than 5 mm in diameter. Five millimeter has been applied in many studies as the cut off tumor size in recent years. In this study, we would like to analyze the clinicopathological and ultrasonographic features of papillary thyroid microcarcinoma (PTMC) ≤5 mm and >5 mm with the aim of finding out the diagnostic value of ultrasonography. SUBJECTS AND METHODS: A total of 291 patients from January 2012 to October 2014 who underwent an ultrasound examination and were postoperatively diagnosed as PTMC were enrolled in the study. The patients were divided into Group A (≤5 mm) and Group B (>5 mm, ≤10 mm) based on diameter. The clinicopathological and ultrasonographic features of the two groups were statistically analyzed. RESULTS: In total, 291 thyroid tumors were analyzed in 291 patients. In patients who were identified with multiple tumors, the largest nodule in size was used for analysis. PTMC >5 mm in diameter were found with a higher incidence of lymph node metastasis and advanced tumor-node-metastasis (TNM) Stage (III/IV) with a significant difference, also with a larger part of multiple tumors compared to PTMC <5 mm. Of all the ultrasonographic features studied, calcification and peripheral halo were more significantly correlated with PTMC >5 mm. The presence of vascularity and blood supply were both associated with the tumor size. CONCLUSION: Larger tumor size of PTMC is more likely to involve in lymph node metastasis and advanced TNM stage. Correlation of tumor size with calcification, peripheral halo, vascularity, and blood supply do exist in PTMC. Ultrasound is of great value in the evaluation of PTMC.

A Single-Center Retrospective Validation Study of the American College of Radiology Thyroid Imaging Reporting and Data System.

OBJECTIVE: This study aimed to evaluate a new risk stratification system, the American College of Radiology (ACR) Thyroid Imaging Reporting and Data System (TI-RADS), published in 2017. MATERIALS AND METHODS: From January 2015 to December 2016, 1033 thyroid nodules in 1013 patients who had undergone sonography and thyroid surgery or fine-needle aspiration (FNA) in our hospital were included. The sonographic features were described in a standard manner and analyzed according to the white paper of the ACR TI-RADS Committee. Nodules were assigned points for each feature, and the points were totaled to determine the final TI-RADS levels. RESULTS: Of the 1033 nodules, 725 were benign and 308 were malignant proven by operation or FNA. The malignant risk was associated with the composition, echogenicity, shape, margins, and echogenic foci of the nodules (P < 0.001). The calculated risk of malignancy was higher in nodules with macrocalcifications than those with peripheral calcifications, which is different from the ACR TI-RADS. The calculated malignancy rates of nodules with TR5, TR4, TR3, and TR2 were 67.1%, 13.0%, 1.1%, and 0%, respectively, which showed a higher malignant risk than the suggested threshold of TR5 in the ACR TI-RADS. Six nodules with TR4 recommended for no follow-up and 55 nodules with TR5 recommended for follow-up were malignant with cervical lymph node metastasis. CONCLUSIONS: The ACR TI-RADS provides effective malignancy risk stratification for thyroid nodules and was useful for the decision for FNA. However, the points assigned for echogenic foci, the set of the TI-RADS risk thresholds, and FNA thresholds may need more consideration and prospective validation.

Associations of Age, BMI, and Years of Menstruation with Proximal Femur Strength in Chinese Postmenopausal Women: A Cross-Sectional Study.

This study aimed to elucidate the associations of age, BMI, and years of menstruation with proximal femur strength in Chinese postmenopausal women, which may improve the prediction of hip fracture risk. A cross-sectional study was conducted in 1322 Chinese postmenopausal women recruited from communities. DXA images were used to generate bone mineral density (BMD) and geometric parameters, including cross-sectional area (CSA), outer diameter (OD), cortical thickness (CT), section modulus (SM), buckling ratio (BR) at the narrow neck (NN), intertrochanter (IT), and femoral shaft (FS). Relationships of age, BMI, and years of menstruation with bone phenotypes were analyzed with the adjustment of height, age at menarche, total daily physical activity, education, smoking status, calcium tablet intake, etc. Age was associated with lower BMD, CSA, CT, SM, and higher BR (p < 0.05), which indicated a weaker bone strength at the proximal femur. BMI and years of menstruation had the positive relationships with proximal femur strength (p < 0.05). Further analyses showed that the ranges of absolute value of change slope per year, per BMI or per year of menstruation were 0.14%-1.34%, 0.20%-2.70%, and 0.16%-0.98%, respectively. These results supported that bone strength deteriorated with aging and enhanced with higher BMI and longer time of years of menstruation in Chinese postmenopausal women.