Hyperglycemia-induced oxidative stress exacerbates mitochondrial apoptosis damage to cochlear stria vascularis pericytes via the ROS-mediated Bcl-2/CytC/AIF pathway.

OBJECTIVES: Diabetes is closely linked to hearing loss, yet the exact mechanisms remain unclear. Cochlear stria vascularis and pericytes (PCs) are crucial for hearing. This study investigates whether high glucose induces apoptosis in the cochlear stria vascularis and pericytes via elevated ROS levels due to oxidative stress, impacting hearing loss. METHODS: We established a type II diabetes model in C57BL/6J mice and used auditory brainstem response (ABR), Evans blue staining, HE staining, immunohistochemistry, and immunofluorescence to observe changes in hearing, blood-labyrinth barrier (BLB) permeability, stria vascularis morphology, and apoptosis protein expression. Primary cultured stria vascularis pericytes were subjected to high glucose, and apoptosis levels were assessed using flow cytometry, Annexin V-FITC, Hoechst 33342 staining, Western blot, Mitosox, and JC-1 probes. RESULTS: Diabetic mice showed decreased hearing thresholds, reduced stria vascularis density, increased oxidative stress, cell apoptosis, and decreased antioxidant levels. High glucose exposure increased apoptosis and ROS content in pericytes, while mitochondrial membrane potential decreased, with AIF and cytochrome C (CytC) released from mitochondria to the cytoplasm. Adding oxidative scavengers reduced AIF and CytC release, decreasing pericyte apoptosis. DISCUSSION: Hyperglycemia may induce mitochondrial apoptosis of cochlear stria vascularis pericytes through oxidative stress.

Se-methylselenocysteine inhibits the progression of non-small cell lung cancer via ROS-mediated NF-κB signaling pathway.

Se-methylselenocysteine (MSC) is recognized for its potential in cancer prevention, yet the specific effects and underlying processes it initiates within non-small cell lung cancer (NSCLC) remain to be fully delineated. Employing a comprehensive array of assays, including CCK-8, colony formation, flow cytometry, MitoSOX Red staining, wound healing, transwell, and TUNEL staining, we evaluated MSC's effects on A549 and 95D cell lines. Our investigation extended to the ROS-mediated NF-κB signaling pathway, utilizing Western blot analysis, P65 overexpression, and the application of IκB-α inhibitor (BAY11-7082) or N-acetyl-cysteine (NAC) to elucidate MSC's mechanism of action. In vivo studies involving subcutaneous xenografts in mice further confirmed MSC's inhibitory effect on tumor growth. Our findings indicated that MSC inhibited the proliferation of A549 and 95D cells, arresting cell cycle G0/G1 phase and reducing migration and invasion, while also inducing apoptosis and increasing intracellular ROS levels. This was accompanied by modulation of key proteins, including the upregulation of p21, p53, E-cadherin, Bax, cleaved caspase-3, cleaved-PARP, and downregulation of CDK4, SOD2, GPX-1. MSC was found to inhibit the NF-κB pathway, as evidenced by decreased levels of P-P65 and P-IκBα. Notably, overexpression of P65 and modulation of ROS levels with NAC could attenuate MSC's effects on cellular proliferation and metastasis. Moreover, MSC significantly curtailed tumor growth in vivo and disrupted the NF-κB signaling pathway. In conclusion, our research demonstrates that MSC exhibits anticancer effects against NSCLC by modulating the ROS/NF-κB signaling pathway, suggesting its potential as a therapeutic agent in NSCLC treatment.

Insight into the research history and trends of total anomalous pulmonary venous connection: a bibliometric analysis.

BACKGROUND: Total anomalous pulmonary venous connection (TAPVC) is a rare congenital heart disease characterized by the inability of all pulmonary veins to connect to the left atrium. Our previous bibliometric article summarized the characteristics of only the 100 most cited papers in TAPVC research. The purpose of this study was to use comprehensive bibliometric analysis to examine the development history, current status, and future trends in the field of TAPVC. METHODS: All publications on TAPVC published between 2000 and 2023 were collected from the Web of Science Core Collection. The publication and citation data were quantitatively analyzed by publication year, country, institution, author, and journal. Co-authorship and co-occurrence analyses were performed using VOSviewer, and keyword and reference bursts were identified using CiteSpace. Pearson's test was used to examine the correlations between two continuous variables. RESULTS: As of July 20, 2023, we identified 368 publications with 3320 citations. These publications were published in 132 journals and authored by 1835 researchers from 457 institutions in 47 countries. For the number of publications, the top country, top institution, top author, and top journals were the United States (n = 82), Shanghai Jiao Tong University (n = 13), Huiwen Chen (n = 9), and Annals of Thoracic Surgery and Pediatric Cardiology (n = 29 each), respectively. For the number of citations, the top country, top affiliation, top author, and top journal were the United States (n = 1348), University of Toronto (n = 250), Christopher A. Caldarone (n = 315), and Annals of Thoracic Surgery (n = 746), respectively. The number of national publications significantly correlated with GDP (R = 0.887, P < 0.001), research & development (R&D) expenditure (R = 0.375, P = 0.013), population (R = 0.694, P < 0.001), and journals (R = 0.751, P < 0.001). The number of national citations significantly correlated with GDP (R = 0.881, P < 0.001), R&D expenditure (R = 0.446, P = 0.003), population (R = 0.305, P = 0.037), and journals (R = 0.917, P < 0.001). International collaboration in the field of TAPVC was not well developed. The most commonly cited publication discussed era changes in mortality and reoperation rate in TAPVC patients. The most common keywords were "total anomalous pulmonary venous connection" and "congenital heart disease". The keyword "case report" appeared most recently, with an average occurrence year of 2021.8. The co-occurrence analysis grouped 26 keywords into six themes: surgical repair of TAPVC, postoperative pulmonary vein stenosis, surgical repair of TAPVC patients with heterotaxy, application of echocardiography in diagnosing TAPVC, application of echocardiography in the prenatal diagnosis of TAPVC, and application of the sutureless technique in the surgical repair of TAPVC patients with right atrial isomerism or a single ventricle. Citation burst detection identified 32 references with citation bursts, seven of which had ongoing citation bursts until 2023. CONCLUSIONS: This study conducted a bibliometric analysis to provide a comprehensive overview of TAPVC research. We hope to offer new ideas for promoting development in the field of TAPVC.

Continuous Kalman Estimation Method for Finger Kinematics Tracking from Surface Electromyography.

Deciphering hand motion intention from surface electromyography (sEMG) encounters challenges posed by the requisites of multiple degrees of freedom (DOFs) and adaptability. Unlike discrete action classification grounded in pattern recognition, the pursuit of continuous kinematics estimation is appreciated for its inherent naturalness and intuitiveness. However, prevailing estimation techniques contend with accuracy limitations and substantial computational demands. Kalman estimation technology, celebrated for its ease of implementation and real-time adaptability, finds extensive application across diverse domains. This study introduces a continuous Kalman estimation method, leveraging a system model with sEMG and joint angles as inputs and outputs. Facilitated by model parameter training methods, the approach deduces multiple DOF finger kinematics simultaneously. The method's efficacy is validated using a publicly accessible database, yielding a correlation coefficient (CC) of 0.73. With over 45,000 windows for training Kalman model parameters, the average computation time remains under 0.01 s. This pilot study amplifies its potential for further exploration and application within the realm of continuous finger motion estimation technology.

Precise and automated lung cancer cell classification using deep neural network with multiscale features and model distillation.

Lung diseases globally impose a significant pathological burden and mortality rate, particularly the differential diagnosis between adenocarcinoma, squamous cell carcinoma, and small cell lung carcinoma, which is paramount in determining optimal treatment strategies and improving clinical prognoses. Faced with the challenge of improving diagnostic precision and stability, this study has developed an innovative deep learning-based model. This model employs a Feature Pyramid Network (FPN) and Squeeze-and-Excitation (SE) modules combined with a Residual Network (ResNet18), to enhance the processing capabilities for complex images and conduct multi-scale analysis of each channel's importance in classifying lung cancer. Moreover, the performance of the model is further enhanced by employing knowledge distillation from larger teacher models to more compact student models. Subjected to rigorous five-fold cross-validation, our model outperforms existing models on all performance metrics, exhibiting exceptional diagnostic accuracy. Ablation studies on various model components have verified that each addition effectively improves model performance, achieving an average accuracy of 98.84% and a Matthews Correlation Coefficient (MCC) of 98.83%. Collectively, the results indicate that our model significantly improves the accuracy of disease diagnosis, providing physicians with more precise clinical decision-making support.

Alfalfa xeno-miR159a regulates bovine mammary epithelial cell proliferation and milk protein synthesis by targeting PTPRF.

Milk protein content is an important index to evaluate the quality and nutrition of milk. Accumulating evidence suggests that microRNAs (miRNAs) play important roles in bovine lactation, but little is known regarding the cross-kingdom regulatory roles of plant-derived exogenous miRNAs (xeno-miRNAs) in milk protein synthesis, particularly the underlying molecular mechanisms. The purpose of this study was to explore the regulatory mechanism of alfalfa-derived xeno-miRNAs on proliferation and milk protein synthesis in bovine mammary epithelial cells (BMECs). Our previous study showed that alfalfa miR159a (mtr-miR159a, xeno-miR159a) was highly expressed in alfalfa, and the abundance of mtr-miR159a was significantly lower in serum and whey from high-protein-milk dairy cows compared with low-protein-milk dairy cows. In this study, mRNA expression was detected by real-time quantitative PCR (qRT-PCR), and casein content was evaluated by enzyme-linked immunosorbent assay (ELISA). Cell proliferation and apoptosis were detected using the cell counting kit 8 (CCK-8) assay, 5-ethynyl-2'-deoxyuridine (EdU) staining, western blot, and flow cytometry. A dual-luciferase reporter assay was used to determine the regulation of Protein Tyrosine Phosphatase Receptor Type F (PTPRF) by xeno-miR159a. We found that xeno-miR159a overexpression inhibited proliferation of BMEC and promoted cell apoptosis. Besides, xeno-miR159a overexpression decreased ß-casein abundance, and increased α-casein and κ-casein abundance in BMECs. Dual-luciferase reporter assay result confirmed that PTPRF is a target gene of xeno-miR159a. These results provide new insights into the mechanism by which alfalfa-derived miRNAs regulate BMECs proliferation and milk protein synthesis.

Cosine convolutional neural network and its application for seizure detection.

Traditional convolutional neural networks (CNNs) often suffer from high memory consumption and redundancy in their kernel representations, leading to overfitting problems and limiting their application in real-time, low-power scenarios such as seizure detection systems. In this work, a novel cosine convolutional neural network (CosCNN), which replaces traditional kernels with the robust cosine kernel modulated by only two learnable factors, is presented, and its effectiveness is validated on the tasks of seizure detection. Meanwhile, based on the cosine lookup table and KL-divergence, an effective post-training quantization algorithm is proposed for CosCNN hardware implementation. With quantization, CosCNN can achieve a nearly 75% reduction in the memory cost with almost no accuracy loss. Moreover, we design a configurable cosine convolution accelerator on Field Programmable Gate Array (FPGA) and deploy the quantized CosCNN on Zedboard, proving the proposed seizure detection system can operate in real-time and low-power scenarios. Extensive experiments and comparisons were conducted using two publicly available epileptic EEG databases, the Bonn database and the CHB-MIT database. The results highlight the performance superiority of the CosCNN over traditional CNNs as well as other seizure detection methods.

Quercetin attenuates cisplatin-induced mitochondrial apoptosis via PI3K/Akt mediated inhibition of oxidative stress in pericytes and improves the blood labyrinth barrier permeability.

Cisplatin (CDDP) is broadly employed to treat different cancers, whereas there are no drugs approved by the Food and Drug Administration (FDA) for preventing its side effects, including ototoxicity. Quercetin (QU) is a widely available natural flavonoid compound with anti-tumor and antioxidant properties. The research was designed to explore the protective effects of QU on CDDP-induced ototoxicity and its underlying mechanisms in male C57BL/6 J mice and primary cultured pericytes (PCs). Hearing changes, morphological changes of stria vascularis, blood labyrinth barrier (BLB) permeability and expression of apoptotic proteins were observed in vivo by using the auditory brainstem response (ABR) test, HE staining, Evans blue staining, immunohistochemistry, western blotting, etc. Oxidative stress levels, mitochondrial function and endothelial barrier changes were observed in vitro by using DCFH-DA probe detection, flow cytometry, JC-1 probe, immunofluorescence and the establishment in vitro BLB models, etc. QU pretreatment activates the PI3K/AKT signaling pathway, inhibits CDDP-induced oxidative stress, protects mitochondrial function, and reduces mitochondrial apoptosis in PCs. However, PI3K/AKT specific inhibitor (LY294002) partially reverses the protective effects of QU. In addition, in vitro BLB models were established by coculturing PCs and endothelial cells (ECs), which suggests that QU both reduces the CDDP-induced apoptosis in PCs and improves the endothelial barrier permeability. On the whole, the research findings suggest that QU can be used as a novel treatment to reduce CDDP-induced ototoxicity.

Hypofractionated radiotherapy for refractory or relapsed aggressive B-cell lymphoma in the rituximab era.

BACKGROUND: Radiotherapy (RT) is an effective and available local treatment for patients with refractory or relapsed (R/R) aggressive B-cell lymphomas. However, the value of hypofractionated RT in this setting has not been confirmed. METHODS: We retrospectively analyzed patients with R/R aggressive B-cell lymphoma who received hypofractionated RT between January 2020 and August 2022 at a single institution. The objective response rate (ORR), overall survival (OS), progression-free survival (PFS) and acute side effects were analyzed. RESULTS: A total of 30 patients were included. The median dose for residual disease was 36 Gy, at a dose per fraction of 2.3-5 Gy. After RT, the ORR and complete response (CR) rates were 90% and 80%, respectively. With a median follow-up of 10 months (range, 2-27 months), 10 patients (33.3%) experienced disease progression and three died. The 1-year OS and PFS rates for all patients were 81.8% and 66.3%, respectively. The majority (8/10) of post-RT progressions involved out-of-field relapses. Patients with relapsed diseases, no response to systemic therapy, multiple lesions at the time of RT, and no response to RT were associated with out-of-field relapses. PFS was associated with response to RT (P = 0.001) and numbers of residual sites (P < 0.001). No serious non-hematological adverse effects (≥ grade 3) associated with RT were reported. CONCLUSION: These data suggest that hypofractionated RT was effective and tolerable for patients with R/R aggressive B-cell lymphoma, especially for those that exhibited localized residual disease.

Comparing the efficacy and safety of low, medium, and high dosages of selexipag for treating pulmonary hypertension: A systematic review and meta-analysis.

BACKGROUND: The maintenance dosage of selexipag is categorized as low, medium or high. In order to assess the efficacy and safety of different dosages of selexipag for the risk stratification of pulmonary arterial hypertension (PAH), we performed a systematic review and meta-analysis. METHODS: Studies assessing PAH risk stratification indices, such as the World Health Organization functional class (WHO-FC), six-minute walk distance (6MWD), N-terminal pro-B-type natriuretic peptide (NT-proBNP) level, right atrial pressure (RAP), cardiac index (CI) and mixed venous oxygen saturation (SvO2), were included. RESULTS: Thirteen studies were included. Selexipag led to improvements in the 6MWD (MD: 24.20 m, 95% CI: 10.74-37.67), NT-proBNP (SMD: -0.41, 95% CI: -0.79-0.04), CI (MD: 0.47 L/min/m2, 95% CI: 0.17-0.77) and WHO-FC (OR: 0.564, 95% CI: 0.457-0.697). Subgroup analysis demonstrated that all three dosages improved the 6MWD. A moderate dosage led to improvements in the CI (MD: 0.30 L/min/m2, 95% CI: 0.15-0.46) and WHO-FC (OR: 0.589, 95% CI: 0.376-0.922). Within 6 months of treatment, only the WHO-FC and CI were significantly improved (OR: 0.614, 95% CI: 0.380-0.993; MD: 0.30 L/min/m2, 95% CI: 0.16-0.45, respectively). More than 6 months of treatment significantly improved the 6MWD, WHO-FC and NT-proBNP (MD: 40.87 m, 95% CI: 10.97-70.77; OR: 0.557, 95% CI: 0.440-0.705; SMD: -0.61, 95% CI: -1.17-0.05, respectively). CONCLUSIONS: Low, medium, and high dosages of selexipag all exhibited good effects. When treatment lasted for more than 6 months, selexipag exerted obvious effects, even in the low-dosage group. This finding is important for guiding individualized treatments.

Pseudo-equilibrium equations for calcium phosphate precipitation with multi-unit particles.

The chemistry underlying bone mineral formation in vertebrates is the reaction of calcium phosphate precipitation. In a near-neutral solution, an amorphous phase and hydroxyapatite nanoparticles appear successively, and the reaction system containing either of the two kinds of precipitates is in a non-equilibrium state. Here, we propose a pseudo-equilibrium approach to the solution chemistry of the precipitation reactions. We employed two series of reaction systems, collected samples at various stages, and analyzed the solution chemistry data on the basis of a simplified model of reaction. We derived two types of pseudo-equilibrium equations from the two series, respectively. These equations reveal the existence of multiple structural units in a precipitate particle and correlate the ionic product with the surface proportion per structural unit (m). The surface proportion, in turn, is related to the whole particle through a particle-surface equation. Notably, the two types of pseudo-equilibrium constants have the common expression of "Kd = ionic product" if the number of the structural units (u) is large enough. Together, these findings have revealed some aspects of the non-equilibrium thermodynamics of precipitation reactions, indicating the solution chemistry route to the equilibrium state. The concept of the multi-unit particle may shed new light on the study of precipitation reactions of other slightly soluble electrolytes. And the relationship between the ionic product and the surface proportion of a structural unit is not only fundamental in chemistry, but may also apply to non-equilibrium systems in nature and biology, such as marine sedimentation, human vascular calcification, and bone mineral metabolism.

Palladium-catalyzed decarboxylative α-allylation of thiazolidinones and azlactones with sulfonamido-substituted acyclic allylic carbonates.

A palladium-catalyzed decarboxylative α-allylation of thiazolidinones and azlactones with aza-π-allylpalladium zwitterionic intermediates, in situ generated from sulfonamido-substituted allylic carbonates, is successfully developed. This method allows the formation of a series of structurally diverse 5-alkylated thiazolidinones and 2-piperidones under mild conditions in moderate to high yields (up to 99% yield).

Death education for undergraduate nursing students in the China Midwest region: An exploratory analysis.

AIM: The purpose of this study was to comprehend the need for incorporating death education within the curriculum of undergraduate nursing students and to assess the factors that impact the desire for such education. DESIGN: We enlisted undergraduate nursing students from several nursing colleges located in the central and west region of China. Undergraduate students who fulfilled the eligibility criteria between January and February 2021 were chosen to participate. Data were collected via an online platform called Questionnaire Star. The survey encompassed a general information questionnaire and a scale for assessing the need for education on the topic of death. Descriptive statistical analysis was performed using the SPSS 20.0 software, while multivariate stepwise regression was employed for more complex analysis. Statistical significance was indicated when the p-value was below 0.05, and high statistical significance was noted when the p-value fell below 0.01. METHODS: We designed a descriptive quantitative approach to investigate the need for death education and its associated factors. The research involved 907 undergraduate nursing students from the central and west region of China. The data collection was done through the Questionnaire Star platform. RESULTS: Following the collection of completed surveys, individuals displaying contradictory responses were omitted. Out of 911 surveys disseminated, 907 were successfully collected, resulting in a recovery rate of 99.6%. Among the participants, 769 identified as female, constituting 84.8% of the total, while 138 identified as male, making up 15.2%. The survey findings indicated that factors such as residency, parental educational history and exposure to hospice care education significantly impacted the need for death education among undergraduate nurses (p < 0.05). CONCLUSIONS: Among students pursuing a nursing degree at the undergraduate level, there was a pronounced need for education related to the topic of death. Offering such education to these students is essential, as it helps cultivate a proper understanding of death. This, in turn, contributes to enhancing the overall quality of patient care throughout their life journey. PATIENT OR PUBLIC CONTRIBUTION: A total of 907 nursing undergraduates from central and western China participated in the questionnaire.

The Effect of Social Network Use on Chinese College Students' Conspicuous Consumption: A Moderated Mediation Model.

This study explored the effects of social networking site use intensity, upward social comparison, and optimism on college students' conspicuous consumption and their mechanisms of action using a sample of Chinese college students. A total of 717 Chinese college students (M = 20.08, SD = 1.44; 73.9% female) completed the Social Network Use Intensity Scale, the Upward Social Comparison Scale, the Life Orientation Test, and the Conspicuous Consumption Scale. The results indicate that (1) the intensity of use of social networking sites significantly positively predicts the conspicuous consumption behavior of college students; (2) upward social comparison plays a mediating role between the intensity of social networking site usage and conspicuous consumption; and (3) optimism moderates the second half of the mediating path between the intensity of social networking site use, upward social comparison, and conspicuous consumption. Specifically, the relationship between upward social comparison and conspicuous consumption among college students with low optimism levels is stronger than that among college students with high levels of optimism. Intensity has a stronger positive effect on conspicuous consumption through upward social comparison. It is concluded that the intensity of college students' use of social networking sites can affect their conspicuous consumption behavior through upward social comparison, and this relationship is moderated by optimism. The results of the study help to reveal the influence of SNS (social networking site) use behavior on conspicuous consumption and its mechanism of action and have implications for reducing the negative impact of conspicuous consumption on college students.

An Approach for EEG Denoising Based on Wasserstein Generative Adversarial Network.

Electroencephalogram (EEG) recordings often contain artifacts that would lower signal quality. Many efforts have been made to eliminate or at least minimize the artifacts, and most of them rely on visual inspection and manual operations, which is time/labor-consuming, subjective, and incompatible to filter massive EEG data in real-time. In this paper, we proposed a deep learning framework named Artifact Removal Wasserstein Generative Adversarial Network (AR-WGAN), where the well-trained model can decompose input EEG, detect and delete artifacts, and then reconstruct denoised signals within a short time. The proposed approach was systematically compared with commonly used denoising methods including Denoised AutoEncoder, Wiener Filter, and Empirical Mode Decomposition, with both public and self-collected datasets. The experimental results proved the promising performance of AR-WGAN on automatic artifact removal for massive data across subjects, with correlation coefficient up to 0.726±0.033, and temporal and spatial relative root-mean-square error as low as 0.176±0.046 and 0.761±0.046, respectively. This work may demonstrate the proposed AR-WGAN as a high-performance end-to-end method for EEG denoising, with many on-line applications in clinical EEG monitoring and brain-computer interfaces.

In-vitro quantitative measurement and analysis of the photosensitivity of cells to a weak pulse laser.

Light can trigger electrical activity in certain types of cells, and is considered to be a better means of biological regulation than electrical stimulation in the future. Due to the specificity and selectivity of natural cells' photoresponse to optical signals, constructing an applicable method to explore which kinds of cells have photosensitivity and which bands of light could induce its photoresponse most effectively, is of great significance for lights' medical applications. This paper firstly proposed a universal and operable system and corresponding method to quantitatively measure and analyze photosensitivity of cells in vitro to weak pulse laser, which is constructed with Ca2+ imaging module, adjustable laser lights module and laser positioning module. With the measurement system and method, the photosensitive effects of the natural spiral ganglion cells (SGCs) of mice are tested systemantically. Then a new photoresponse band of light (453 nm, 300 µs) is found for SGCs, and its minimum threshold is measured as 5.3 mJ/cm2. The results verify that the proposed method is applicable to screen the cells with photosensitive response, as well as to measure and analyze the working optical parameters, thus is beneficial for the optical biophysics and photobiology.

Prediction of treatment response to antipsychotic drugs for precision medicine approach to schizophrenia: randomized trials and multiomics analysis.

BACKGROUND: Choosing the appropriate antipsychotic drug (APD) treatment for patients with schizophrenia (SCZ) can be challenging, as the treatment response to APD is highly variable and difficult to predict due to the lack of effective biomarkers. Previous studies have indicated the association between treatment response and genetic and epigenetic factors, but no effective biomarkers have been identified. Hence, further research is imperative to enhance precision medicine in SCZ treatment. METHODS: Participants with SCZ were recruited from two randomized trials. The discovery cohort was recruited from the CAPOC trial (n = 2307) involved 6 weeks of treatment and equally randomized the participants to the Olanzapine, Risperidone, Quetiapine, Aripiprazole, Ziprasidone, and Haloperidol/Perphenazine (subsequently equally assigned to one or the other) groups. The external validation cohort was recruited from the CAPEC trial (n = 1379), which involved 8 weeks of treatment and equally randomized the participants to the Olanzapine, Risperidone, and Aripiprazole groups. Additionally, healthy controls (n = 275) from the local community were utilized as a genetic/epigenetic reference. The genetic and epigenetic (DNA methylation) risks of SCZ were assessed using the polygenic risk score (PRS) and polymethylation score, respectively. The study also examined the genetic-epigenetic interactions with treatment response through differential methylation analysis, methylation quantitative trait loci, colocalization, and promoter-anchored chromatin interaction. Machine learning was used to develop a prediction model for treatment response, which was evaluated for accuracy and clinical benefit using the area under curve (AUC) for classification, R2 for regression, and decision curve analysis. RESULTS: Six risk genes for SCZ (LINC01795, DDHD2, SBNO1, KCNG2, SEMA7A, and RUFY1) involved in cortical morphology were identified as having a genetic-epigenetic interaction associated with treatment response. The developed and externally validated prediction model, which incorporated clinical information, PRS, genetic risk score (GRS), and proxy methylation level (proxyDNAm), demonstrated positive benefits for a wide range of patients receiving different APDs, regardless of sex [discovery cohort: AUC = 0.874 (95% CI 0.867-0.881), R2 = 0.478; external validation cohort: AUC = 0.851 (95% CI 0.841-0.861), R2 = 0.507]. CONCLUSIONS: This study presents a promising precision medicine approach to evaluate treatment response, which has the potential to aid clinicians in making informed decisions about APD treatment for patients with SCZ. Trial registration Chinese Clinical Trial Registry ( https://www.chictr.org.cn/ ), 18. Aug 2009 retrospectively registered: CAPOC-ChiCTR-RNC-09000521 ( https://www.chictr.org.cn/showproj.aspx?proj=9014 ), CAPEC-ChiCTR-RNC-09000522 ( https://www.chictr.org.cn/showproj.aspx?proj=9013 ).

Preoperative contrast-enhanced CT-based radiomics nomogram for differentiating benign and malignant primary retroperitoneal tumors.

OBJECTIVES: This study evaluated the ability of a preoperative contrast-enhanced CT (CECT)-based radiomics nomogram to differentiate benign and malignant primary retroperitoneal tumors (PRT). METHODS: Images and data from 340 patients with pathologically confirmed PRT were randomly placed into training (n = 239) and validation sets (n = 101). Two radiologists independently analyzed all CT images and made measurements. Key characteristics were identified through least absolute shrinkage selection combined with four machine-learning classifiers (support vector machine, generalized linear model, random forest, and artificial neural network back propagation) to create a radiomics signature. Demographic data and CECT characteristics were analyzed to formulate a clinico-radiological model. Independent clinical variables were merged with the best-performing radiomics signature to develop a radiomics nomogram. The discrimination capacity and clinical value of three models were quantified by the area under the receiver operating characteristics (AUC), accuracy, and decision curve analysis. RESULTS: The radiomics nomogram was able to consistently differentiate between benign and malignant PRT in the training and validation datasets, with AUCs of 0.923 and 0.907, respectively. Decision curve analysis manifested that the nomogram achieved higher clinical net benefits than did separate use of the radiomics signature and clinico-radiological model. CONCLUSIONS: The preoperative nomogram is valuable for differentiating between benign and malignant PRT; it can also aid in treatment planning. KEY POINTS: • A noninvasive and accurate preoperative determination of benign and malignant PRT is crucial to identifying suitable treatments and predicting disease prognosis. • Associating the radiomics signature with clinical factors facilitates differentiation of malignant from benign PRT with improved diagnostic efficacy (AUC) and accuracy from 0.772 to 0.907 and from 0.723 to 0.842, respectively, compared with the clinico-radiological model alone. • For some PRT with anatomically special locations and when biopsy is extremely difficult and risky, a radiomics nomogram may provide a promising preoperative alternative for distinguishing benignity and malignancy.

Continuous grip force estimation from surface electromyography using generalized regression neural network.

BACKGROUND: Grip force estimation is highly required in realizing flexible and accurate prosthetic control. OBJECTIVE: This study presents a method to accurately estimate continuous grip force from surface electromyography (sEMG) under three forearm postures for unilateral amputees. METHODS: Ten able-bodied subjects and a transradial amputee were recruited. sEMG signals were recorded from six forearm muscles on the dominant side of each able-bodied subject and the stump of amputee. Meanwhile, grip force was synchronously measured from the ipsilateral hands of able-bodied subjects and contralateral hand of amputee. Three force profiles (triangle, trapezoid, and fast triangle) were tested under three forearm postures (supination, neutral and pronation). Two algorithms (Generalized Regression Neural Network (GRNN) and Multilinear Regression Model (MLR)) were compared using several EMG features. The estimation performance was evaluated by coefficient of determination (R2) and mean absolute error (MAE). RESULTS: The optimal regressor combining TD and GRNN achieved R2= 96.33 ± 1.13% and MAE= 2.11 ± 0.52% for the intact subjects, and R2= 86.86% and MAE= 2.13% for the amputee. The results indicated that multiple grip force curves under three forearm postures could be accurately estimated for unilateral amputees using mirrored bilateral training. CONCLUSIONS: The proposed method has the potential for precise force control of prosthetic hands.

Chinese Traditional Medicine Jiangtang Wan ameliorates kidney injury and fîbrosis in mice with diabetic kidney disease via inhibiting TGF-pj / 中国药理学通报

Aim To investigate the therapeutic effect of Jiangtang Wan (JTW) on mioe with diabetic kidney disease (DKD) and to explore its potential moiecuiar mechanism on ameliorating renal injury and fibrosis. Methods C57BL/6 mice were randomly divided into four groups: the control group, the model group, JTW group (1250 mg • kg