Renal nerve stimulation identifies renal innervation and optimizes the strategy for renal denervation in canine.

BACKGROUND: Renal denervation (RDN) was still performed without any intra-procedural method for nerve mapping. Whether renal nerve stimulation (RNS) is an efficient way to identify renal autonomic innervation and optimize the strategy for RDN remain to be worthy for further exploration. METHODS: The characteristics of renal autonomic innervation at the sites with different blood pressure (BP) responses to RNS were explored. Then, dogs anatomically eligible for RDN were randomly assigned into elevated BP response ablation group, reduced BP response ablation group, and RNS-control group. The postoperative outcomes were measured at baseline and after 4 weeks follow-up. RESULTS: The proportion of afferent sensory nerve was higher at elevated BP response sites (ERS) than reduced BP response sites (RRS) and non-response sites (NRS) (P = 0.012 and P = 0.004). Conversely, the proportion of parasympathetic nerve at RRS was the highest (RRS vs. ERS, P = 0.017; RRS vs. NRS, P = 0.023). More importantly, there was a significant correlation between systolic blood pressure changes and the area ratios of afferent sensory and parasympathetic nerve (R = 0.859; P < 0.001). In addition, ablation at BP-elevation sites can result in a significant decrease in BP and plasma norepinephrine (NE) after 4 weeks (P = 0.002; P = 0.008), while ablation at BP-reduction sites can lead to significant increases in BP and plasma NE (P = 0.016; P = 0.033). CONCLUSIONS: RNS is an effective method to identify renal autonomic innervation. It could not only help to identify optimal target sites, but also avoid ablation of sympathetic-inhibitory areas during RDN.

Enhancement of sonodynamic treatment of ovarian cancer based on Pt-B-P ternary nanoparticles.

Sonodynamic therapy (SDT) can noninvasively focus sound energy to deep tumor tissues and activate sonosensitizer (such as chlorin e6(Ce6)) to produce antitumor effects. However, due to the hypoxic microenvironment of the tumor, the effect of sonodynamic therapy is limited. In this work, we successfully synthesized Platinum-Boron-Phosphorus ternary nanoparticles (Pt-B-P NPs) for the first time to efficiently catalyze the decomposition of hydrogen peroxide (H2O2) in tumor tissues to produce sufficient oxygen (O2) and improve the effect of sonodynamic treatment of ovarian cancer. In vitro studies, we found that compared with Platinum nanoparticles (Pt NPs), Pt-B-P NPs have the significantly increased ability to catalyze the decomposition of H2O2 to produce oxygen and thus the hypoxic environment of tumor cells could be improved efficiently. Meanwhile, the bio-distribution, therapeutic effect and bio-safety of Pt-B-P NPs in vivo were evaluated using BALB/c-nu mouse model of ovarian cancer and the desired result had been achieved.

S14G-humanin confers cardioprotective effects against chronic adrenergic and pressure overload-induced heart failure in mice.

S14G-humanin (HNG), an analog of the mitochondria-derived peptide humanin, has demonstrated protective effects against various cardiovascular diseases. However, the specific pharmacological effects of HNG in heart failure (HF) have not been previously reported. Therefore, in this study, we aimed to investigate the potential protective effect of HNG in HF using a mouse model. HF was induced in mice through intraperitoneal injection of isoproterenol or transverse aortic constriction, followed by separate administration of HNG to assess its therapeutic impact. Our results revealed that HNG treatment significantly delayed the onset of cardiac dysfunction and structural remodeling in the HF mouse model. Furthermore, HNG administration was associated with reduced infiltration of inflammatory cells, improved myocardial fibrosis, and attenuation of cardiomyocyte apoptosis in the treated cardiac tissues. Additionally, we identified the involvement of the transforming growth factor-beta signaling pathway in the beneficial effects of HNG in isoproterenol-induced HF mice. Collectively, these findings underscore the therapeutic potential of HNG in preventing the progression of HF, as demonstrated in two distinct HF mouse models.

A Web-Based Prediction Model for Cancer-Specific Survival of Middle-Aged Patients With Non-metastatic Renal Cell Carcinoma: A Population-Based Study.

Background: Renal cell carcinoma (RCC) is one of the most common cancers in middle-aged patients. We aimed to establish a new nomogram for predicting cancer-specific survival (CSS) in middle-aged patients with non-metastatic renal cell carcinoma (nmRCC). Methods: The clinicopathological information of all patients from 2010 to 2018 was downloaded from the SEER database. These patients were randomly assigned to the training set (70%) and validation set (30%). Univariate and multivariate COX regression analyses were used to identify independent risk factors for CSS in middle-aged patients with nmRCC in the training set. Based on these independent risk factors, a new nomogram was constructed to predict 1-, 3-, and 5-year CSS in middle-aged patients with nmRCC. Then, we used the consistency index (C-index), calibration curve, and area under receiver operating curve (AUC) to validate the accuracy and discrimination of the model. Decision curve analysis (DCA) was used to validate the clinical application value of the model. Results: A total of 27,073 patients were included in the study. These patients were randomly divided into a training set (N = 18,990) and a validation set (N = 8,083). In the training set, univariate and multivariate Cox regression analysis indicated that age, sex, histological tumor grade, T stage, tumor size, and surgical method are independent risk factors for CSS of patients. A new nomogram was constructed to predict patients' 1-, 3-, and 5-year CSS. The C-index of the training set and validation set were 0.818 (95% CI: 0.802-0.834) and 0.802 (95% CI: 0.777-0.827), respectively. The 1 -, 3 -, and 5-year AUC for the training and validation set ranged from 77.7 to 80.0. The calibration curves of the training set and the validation set indicated that the predicted value is highly consistent with the actual observation value, indicating that the model has good accuracy. DCA also suggested that the model has potential clinical application value. Conclusion: We found that independent risk factors for CSS in middle-aged patients with nmRCC were age, sex, histological tumor grade, T stage, tumor size, and surgery. We have constructed a new nomogram to predict the CSS of middle-aged patients with nmRCC. This model has good accuracy and reliability and can assist doctors and patients in clinical decision making.

Ultrasound Radiomics Nomogram Integrating Three-Dimensional Features Based on Carotid Plaques to Evaluate Coronary Artery Disease.

This study aimed to explore the feasibility of ultrasound radiomics analysis before invasive coronary angiography (ICA) for evaluating the severity of coronary artery disease (CAD) quantified by the SYNTAX score (SS). This study included 105 carotid plaques from 105 patients (64 low-SS patients, 41 intermediate-high-SS patients). The clinical characteristics and three-dimensional ultrasound (3D-US) features before ICA were assessed. Ultrasound images of carotid plaques were used for radiomics analysis. Least absolute shrinkage and selection operator (LASSO) regression, which generated several nonzero coefficients, was used to select features that could predict intermediate-high SS. Based on those coefficients, the radiomics score (Rad-score) was calculated. The selected clinical characteristics, 3D-US features, and Rad-score were finally integrated into a radiomics nomogram. Among the clinical characteristics and 3D-US features, high-density lipoprotein (HDL), apolipoprotein B (Apo B), and plaque volume were identified as predictors for distinguishing between low SS and intermediate-high SS. During the radiomics process, 8 optimal radiomics features most capable of identifying intermediate-high SS were selected from 851 candidate radiomics features. The differences in Rad-score between the training and the validation set were significant (p = 0.016 and 0.006). The radiomics nomogram integrating HDL, Apo B, plaque volume, and Rad-score showed excellent results in the training set (AUC, 0.741 (95% confidence interval (CI): 0.646-0.835)) and validation set (AUC, 0.939 (95% CI: 0.860-1.000)), with good calibration (mean absolute errors of 0.028 and 0.059 in training and validation sets, respectively). Decision curve analysis showed that the radiomics nomogram could identify patients who could obtain the most benefit. We concluded that the radiomics nomogram based on carotid plaque ultrasound has favorable value for the noninvasive prediction of intermediate-high SS. This radiomics nomogram has potential value for the risk stratification of CAD before ICA and provides clinicians with a noninvasive diagnostic tool.

Explainable machine learning models for predicting 30-day readmission in pediatric pulmonary hypertension: A multicenter, retrospective study.

Background: Short-term readmission for pediatric pulmonary hypertension (PH) is associated with a substantial social and personal burden. However, tools to predict individualized readmission risk are lacking. This study aimed to develop machine learning models to predict 30-day unplanned readmission in children with PH. Methods: This study collected data on pediatric inpatients with PH from the Chongqing Medical University Medical Data Platform from January 2012 to January 2019. Key clinical variables were selected by the least absolute shrinkage and the selection operator. Prediction models were selected from 15 machine learning algorithms with excellent performance, which was evaluated by area under the operating characteristic curve (AUC). The outcome of the predictive model was interpreted by SHapley Additive exPlanations (SHAP). Results: A total of 5,913 pediatric patients with PH were included in the final cohort. The CatBoost model was selected as the predictive model with the greatest AUC for 0.81 (95% CI: 0.77-0.86), high accuracy for 0.74 (95% CI: 0.72-0.76), sensitivity 0.78 (95% CI: 0.69-0.87), and specificity 0.74 (95% CI: 0.72-0.76). Age, length of stay (LOS), congenital heart surgery, and nonmedical order discharge showed the greatest impact on 30-day readmission in pediatric PH, according to SHAP results. Conclusions: This study developed a CatBoost model to predict the risk of unplanned 30-day readmission in pediatric patients with PH, which showed more significant performance compared with traditional logistic regression. We found that age, LOS, congenital heart surgery, and nonmedical order discharge were important factors for 30-day readmission in pediatric PH.

Activation of TRPV4 by lactate as a critical mediator of renal fibrosis in spontaneously hypertensive rats after moderate- and high-intensity exercise.

Moderate-intensity exercise training has been regarded a healthy way to alleviate kidney fibrosis by the transforming growth factor-beta (TGFß) signaling pathway. However, the impact of different intensity exercise training on renal function is unknown, and the underlying mechanism is also unclear. The purpose of this study is to explore the effect of lactic acid in different intensity exercise training on renal fibrosis in spontaneous hypertension. Masson's trichrome staining, immunohistochemistry, lactic acid kit, and Western blotting were applied on the excised renal tissue from six male Wistar-Kyoto rats (WKY) and 18 male spontaneously hypertensive rats (SHR), which were randomly divided into a sedentary hypertensive group (SHR), moderate-intensity exercise hypertensive group (SHR-M), and high-intensity exercise hypertensive group (SHR-H). The results revealed that renal and blood lactic acid, as well as the key fibrotic protein levels of transient receptor potential vanilloid 4 (TRPV4), TGFß-1, phospho-Smad2/3 (p-Smad2/3), and connective tissue growth factor (CTGF), were significantly decreased in the SHR-M group when compared with the SHR and SHR-H groups. In further in vitro experiments, we selected normal rat kidney interstitial fibroblast (NRK-49F) cells. By immunofluorescence and Western blotting techniques, we found that TRPV4 antagonists (RN-1734) markedly inhibited lactate-induced fibrosis. In conclusion, compared with previous studies, high-intensity exercise training (HIET) can cause adverse effects (renal damage and fibrosis). High concentrations of lactic acid can aggravate renal fibrosis conditions via activating TRPV4-TGFß1-SMAD2/3-CTGF-mediated renal fibrotic pathways in spontaneous hypertension. This finding might provide new ideas for treating hypertensive nephropathy with different intensity exercise in the future.

Risk Stratification Model for Predicting the Overall Survival of Elderly Triple-Negative Breast Cancer Patients: A Population-Based Study.

Background: The objective of this study was to evaluate the prognostic value of clinical characteristics in elderly patients with triple-negative breast cancer (TNBC). Methods: The cohort was selected from the Surveillance, Epidemiology, and End Results (SEER) program dating from 2010 to 2015. Univariate and multivariate analyses were performed using a Cox proportional risk regression model, and a nomogram was constructed to predict the 1-, 3-, and 5-year prognoses of elderly patients with TNBC. A concordance index (C-index), calibration curve, and decision curve analysis (DCA) were used to verify the nomogram. Results: The results of the study identified a total of 5,677 patients who were randomly divided 6:4 into a training set (n = 3,422) and a validation set (n = 2,255). The multivariate analysis showed that age, race, grade, TN stage, chemotherapy status, radiotherapy status, and tumor size at diagnosis were independent factors affecting the prognosis of elderly patients with TNBC. Together, the 1 -, 3 -, and 5-year nomograms were made up of 8 variables. For the verification of these results, the C-index of the training set and validation set were 0.757 (95% CI 0.743-0.772) and 0.750 (95% CI 0.742-0.768), respectively. The calibration curve also showed that the actual observation of overall survival (OS) was in good agreement with the prediction of the nomograms. Additionally, the DCA showed that the nomogram had good clinical application value. According to the score of each patient, the risk stratification system of elderly patients with TNBC was further established by perfectly dividing these patients into three groups, namely, low risk, medium risk, and high risk, in all queues. In addition, the results showed that radiotherapy could improve prognosis in the low-risk group (P = 0.00056), but had no significant effect in the medium-risk (P < 0.4) and high-risk groups (P < 0.71). An online web app was built based on the proposed nomogram for convenient clinical use. Conclusion: This study was the first to construct a nomogram and risk stratification system for elderly patients with TNBC. The well-established nomogram and the important findings from our study could guide follow-up management strategies for elderly patients with TNBC and help clinicians improve individual treatment.