Kemin capsule ameliorates post-infectious cough by modulating the PI3K/AKT signaling pathway and TRPA1/TRPV1 channels.

ETHNOPHARMACOLOGICAL RELEVANCE: Kemin capsule (KMC), as an innovative traditional Chinese medicine (TCM), has shown excellent efficacy in treating PIC in China. The post-infectious cough (PIC) is a common condition in pediatrics, and the inflammatory responses to PIC are intricately linked to the immune mechanisms of the host. However, the precise mechanisms involved remain uncertain. AIM OF STUDY: The objective of this research is to investigate the mechanisms by which KMC treats PIC using a combination of UPLC-MS, bioinformatics, network pharmacology, and molecular docking. The study's findings will be corroborated through in vitro and in vivo experiments. MATERIALS AND METHODS: This study identified the main components of KMC using UPLC-MS. The mechanism by which these capsules treat PIC was explored through transcriptomics, network pharmacology, and molecular docking. PIC model in Balb/c mice was induced with respiratory syncytial virus (RSV) at a titer of 10^5.5 TCID50/mL. From day 14 post-infection, the mice were orally administered the capsules at doses of 0.3, 0.6, and 1.2 g/kg for two weeks. Cough was stimulated with capsaicin at 10^-4 mol/mL, and the effects on PIC mice were measured by cough frequency, latency, ELISA, and H&E staining. Expression levels of transient receptor potential (TRP) channel proteins and the PI3K/AKT signaling pathway were analyzed using RT-qPCR, immunohistochemistry (IHC), and western blot (WB). The effect of KMC on A549 cells proliferation in vitro was also assessed. RESULTS: The therapeutic efficacy of KMC is potentially exerted through its inherent bioactive constituents, including deoxyandrographolide, quercetin, and chryseriol. These compounds are hypothesized to modulate the PI3K/AKT signaling pathway and influence the function of TRP channel proteins, consequently mitigating the pathological state associated with PIC. In vivo experiments have demonstrated that KMC significantly reduces the frequency of coughs and extends the cough latency period in mice with PIC. KMC mitigates airway inflammation by suppressing the production of pro-inflammatory cytokines, including TNF-α, IL-1ß, and IL-6. The expression or phosphorylation levels of key regulators in the PI3K/AKT/TRP axis in mouse lung tissue, including PI3K, AKT, NF-κB p65, TLR4, STAT3, TRPV1, TRPA1 were significantly reduced. CONCLUSION: KMC exerts its therapeutic effect on PIC by dampening the activation of the PI3K/AKT signaling pathway and the activity of TRPA1 and TRPV1 ion channels.

Optimizing coronary CT angiography quality with motion-compensated reconstruction for second-generation dual-layer spectral detector CT.

OBJECTIVES: To investigate the effect of motion-compensated reconstruction (MCR) algorithm on improving the image quality of coronary computed tomography angiography (CCTA) using second-generation dual-layer spectral detector computed tomography (DLCT), and to evaluate the influence of heart rate (HR) on the motion-correction efficacy of this algorithm. MATERIALS AND METHODS: We retrospectively enrolled 127 patients who underwent CCTA for suspected coronary artery disease using second-generation DLCT. We divided the patients into two subgroups according to their average HR during scanning: the "HR < 75 bpm" group and the "HR ≥ 75 bpm" group. All images were reconstructed by the standard (STD) algorithm and MCR algorithm. Subjective image quality (4-point Likert scale), interpretability, and objective image quality between the STD and MCR in the whole population and within each subgroup were compared. RESULTS: MCR showed significantly higher Likert scores and interpretability than STD on the per-segment (3.58 ± 0.69 vs. 2.82 ± 0.93, 98.4% vs. 91.9%), per-vessel (3.12 ± 0.81 vs. 2.12 ± 0.74, 96.3% vs. 78.7%) and per-patient (2.57 ± 0.76 vs. 1.62 ± 0.55, 90.6% vs. 59.1%) levels (all p < 0.001). In the analysis of HR subgroups on a per-vessel basis of interpretability, significant differences were observed only in the right coronary artery in the low HR group, whereas significant differences were noted in three major coronary arteries in the high HR group. For objective image quality assessment, MCR significantly improved the SNR (13.22 ± 4.06 vs. 12.72 ± 4.06) and the contrast-to-noise ratio (15.84 ± 4.82 vs. 15.39 ± 4.38) compared to STD (both p < 0.001). CONCLUSION: MCR significantly improves the subjective image quality, interpretability, and objective image quality of CCTA, especially in patients with higher HRs. CLINICAL RELEVANCE STATEMENT: The motion-compensated reconstruction algorithm of the second-generation dual-layer spectral detector computed tomography is helpful in improving the image quality of coronary computed tomography angiography in clinical practice, especially in patients with higher heart rates. KEY POINTS: Motion artifacts from cardiac movement affect the quality and interpretability of coronary computed tomography angiography (CCTA). This motion-compensated reconstruction (MCR) algorithm significantly improves the image quality of CCTA in clinical practice. Image quality improvement by using MCR was more significant in the high heart rate group.

Predicting Left Ventricular Adverse Remodeling After Transcatheter Aortic Valve Replacement: A Radiomics Approach.

RATIONALE AND OBJECTIVES: To develop a radiomics model based on cardiac computed tomography (CT) for predicting left ventricular adverse remodeling (LVAR) in patients with severe aortic stenosis (AS) who underwent transcatheter aortic valve replacement (TAVR). MATERIALS AND METHODS: Patients with severe AS who underwent TAVR from January 2019 to December 2022 were recruited. The cohort was divided into adverse remodeling group and non-adverse remodeling group based on LVAR occurrence, and further randomly divided into a training set and a validation set at an 8:2 ratio. Left ventricular radiomics features were extracted from cardiac CT. The least absolute shrinkage and selection operator regression was utilized to select the most relevant radiomics features and clinical features. The radiomics features were used to construct the Radscore, which was then combined with the selected clinical features to build a nomogram. The predictive performance of the models was evaluated using the area under the curve (AUC), while the clinical value of the models was assessed using calibration curves and decision curve analysis. RESULTS: A total of 273 patients were finally enrolled, including 71 with adverse remodeling and 202 with non-adverse remodeling. 12 radiomics features and five clinical features were extracted to construct the radiomics model, clinical model, and nomogram, respectively. The radiomics model outperformed the clinical model (training AUC: 0.799 vs. 0.760; validation AUC: 0.766 vs. 0.755). The nomogram showed highest accuracy (training AUC: 0.859, validation AUC: 0.837) and was deemed most clinically valuable by decision curve analysis. CONCLUSION: The cardiac CT-based radiomics features could predict LVAR after TAVR in patients with severe AS.

Swollen Right Upper Limb in a Man in His 60s Undergoing Hemodialysis.

This case report discusses a diagnosis of in-stent thrombus using dual-layer spectral computed tomography with Z-effective images.

Predicting tumor deposits in rectal cancer: a combined deep learning model using T2-MR imaging and clinical features.

BACKGROUND: Tumor deposits (TDs) are associated with poor prognosis in rectal cancer (RC). This study aims to develop and validate a deep learning (DL) model incorporating T2-MR image and clinical factors for the preoperative prediction of TDs in RC patients. METHODS AND METHODS: A total of 327 RC patients with pathologically confirmed TDs status from January 2016 to December 2019 were retrospectively recruited, and the T2-MR images and clinical variables were collected. Patients were randomly split into a development dataset (n = 246) and an independent testing dataset (n = 81). A single-channel DL model, a multi-channel DL model, a hybrid DL model, and a clinical model were constructed. The performance of these predictive models was assessed by using receiver operating characteristics (ROC) analysis and decision curve analysis (DCA). RESULTS: The areas under the curves (AUCs) of the clinical, single-DL, multi-DL, and hybrid-DL models were 0.734 (95% CI, 0.674-0.788), 0.710 (95% CI, 0.649-0.766), 0.767 (95% CI, 0.710-0.819), and 0.857 (95% CI, 0.807-0.898) in the development dataset. The AUC of the hybrid-DL model was significantly higher than the single-DL and multi-DL models (both p < 0.001) in the development dataset, and the single-DL model (p = 0.028) in the testing dataset. Decision curve analysis demonstrated the hybrid-DL model had higher net benefit than other models across the majority range of threshold probabilities. CONCLUSIONS: The proposed hybrid-DL model achieved good predictive efficacy and could be used to predict tumor deposits in rectal cancer. CRITICAL RELEVANCE STATEMENT: The proposed hybrid-DL model achieved good predictive efficacy and could be used to predict tumor deposits in rectal cancer. KEY POINTS: • Preoperative non-invasive identification of TDs is of great clinical significance. • The combined hybrid-DL model achieved good predictive efficacy and could be used to predict tumor deposits in rectal cancer. • A preoperative nomogram provides gastroenterologist with an accurate and effective tool.

A nomogram for preoperative differentiation of tumor deposits from lymph node metastasis in rectal cancer: A retrospective study.

The objective is to develop and validate a combined model for noninvasive preoperative differentiating tumor deposits (TDs) from lymph node metastasis (LNM) in patients with rectal cancer (RC). A total of 204 patients were enrolled and randomly divided into 2 sets (training and validation set) at a ratio of 8:2. Radiomics features of tumor and peritumor fat were extracted by using Pyradiomics software from the axial T2-weighted imaging of MRI. Rad-score based on extracted Radiomics features were calculated by combination of feature selection and the machine learning method. Factors (Rad-score, laboratory test factor, clinical factor, traditional characters of tumor on MRI) with statistical significance were integrated to build a combined model. The combined model was visualized by a nomogram, and its distinguish ability, diagnostic accuracy, and clinical utility were evaluated by the receiver operating characteristic curve (ROC) analysis, calibration curve, and clinical decision curve, respectively. Carbohydrate antigen (CA) 19-9, MRI reported node stage (MRI-N stage), tumor volume (cm3), and Rad-score were all included in the combined model (odds ratio = 3.881 for Rad-score, 2.859 for CA19-9, 0.411 for MRI-N stage, and 1.055 for tumor volume). The distinguish ability of the combined model in the training and validation cohorts was area under the summary receiver operating characteristic curve (AUC) = 0.863, 95% confidence interval (CI): 0.8-0.911 and 0.815, 95% CI: 0.663-0.919, respectively. And the combined model outperformed the clinical model in both training and validation cohorts (AUC = 0.863 vs 0.749, 0.815 vs 0.627, P = .0022, .0302), outperformed the Rad-score model only in training cohorts (AUC = 0.863 vs 0.819, P = .0283). The combined model had highest net benefit and showed good diagnostic accuracy. The combined model incorporating Rad-score and clinical factors could provide a preoperative differentiation of TD from LNM and guide clinicians in making individualized treatment strategy for patients with RC.

Nomogram including tumor deposition count to noninvasively evaluate the prognosis of rectal cancer patients: A retrospective study.

To build a nomogram model that includes tumor deposition (TDs) count to noninvasively evaluate the prognosis of patients with rectal cancer (RC). A total of 262 patients between January 2013 and December 2018 were recruited and divided into 2 cohorts: training (n = 171) and validation (n = 91). Axial portal venous phase computed tomography images were used to extract radiomic features, and the least absolute shrinkage and selection operator-Cox analysis was applied to develop an optimal radiomics model to derive the Rad-score. A Cox regression model combining clinicopathological factors and Rad-scores was constructed and visualized using a nomogram. And its ability to predict RC patients' survival was tested by Kaplan-Meier survival analysis. The time-dependent concordance index curve was used to demonstrate the differentiation degree of model. Calibration and decision curve analyses were used to evaluate the calibration accuracy and clinical usefulness of the nomogram model, and the prediction performance of the nomogram model was compared with the clinical and radiomics models using the likelihood test. Computed tomography-based Rad-score, pathological tumor (pT) stageT4, and TDs count were independent risk factors affecting the prognosis of RC. The whole concordance index of the nomogram model for predicting the overall survival rates of RC was higher than that of the clinical and radiomics models in the training (0.812 vs 0.59, P = .019; 0.812 vs 0.714, P = .014) and validation groups (0.725 vs 0.585, P = .002; 0.725 vs 0.751, P = .256). The nomogram model could effectively predict patients' overall survival rate (hazard ratio = 9.25, 95% CI = [1.17-72.99], P = .01). The nomogram model also showed a higher clinical net benefit than the clinical and radiomics models in the training and validation groups. The nomogram model developed in this study can be used to noninvasively evaluate the prognosis of RC patients. The TDs count is an independent risk factor for the prognosis of RC.

Metabolomics Provides New Insights into Host Manipulation Strategies by Asobara japonica (Hymenoptera: Braconidae), a Fruit Fly Parasitoid.

Asobara japonica (Hymenoptera: Braconidae) is an endoparasitoid wasp that can successfully parasitize a wide range of host species across the Drosophila genus, including the invasive crop pest Drosophila suzukii. Parasitoids are capable of regulating the host metabolism to produce the nutritional metabolites for the survival of their offspring. Here, we intend to investigate the metabolic changes in D. melanogaster hosts after parasitization by A. japonica, using the non-targeted LC-MS (liquid chromatography-mass spectrometry) metabolomics analysis. In total, 3043 metabolites were identified, most of which were not affected by A. japonica parasitization. About 205 metabolites were significantly affected in parasitized hosts in comparison to non-parasitized hosts. The changed metabolites were divided into 10 distinct biochemical groups. Among them, most of the lipid metabolic substances were significantly decreased in parasitized hosts. On the contrary, most of metabolites associated with the metabolism of amino acids and sugars showed a higher abundance of parasitized hosts, and were enriched for a wide range of pathways. In addition, eight neuromodulatory-related substances were upregulated in hosts post A. japonica parasitization. Our results reveal that the metabolites are greatly changed in parasitized hosts, which might help uncover the underlying mechanisms of host manipulation that will advance our understanding of host-parasitoid coevolution.

Transcriptome Analysis Identifies Key Metabolic Changes in the Brain of Takifugu rubripes in Response to Chronic Hypoxia.

The brain is considered to be an extremely sensitive tissue to hypoxia, and the brain of fish plays an important role in regulating growth and adapting to environmental changes. As an important aquatic organism in northern China, the economic yield of Takifugu rubripes is deeply influenced by the oxygen content of seawater. In this regard, we performed RNA-seq analysis of T. rubripes brains under hypoxia and normoxia to reveal the expression patterns of genes involved in the hypoxic response and their enrichment of metabolic pathways. Studies have shown that carbohydrate, lipid and amino acid metabolism are significant pathways for the enrichment of differentially expressed genes (DEGs) and that DEGs are significantly upregulated in those pathways. In addition, some biological processes such as the immune system and signal transduction, where enrichment is not significant but important, are also discussed. Interestingly, the DEGs associated with those pathways were significantly downregulated or inhibited. The present study reveals the mechanism of hypoxia tolerance in T. rubripes at the transcriptional level and provides a useful resource for studying the energy metabolism mechanism of hypoxia response in this species.

Computed Tomography-Based Radiomics for Differentiation of Thymic Epithelial Tumors and Lymphomas in Anterior Mediastinum.

Objective: To investigate the differential diagnostic performance of computed tomography (CT)-based radiomics in thymic epithelial tumors (TETs) and lymphomas in anterior mediastinum. Methods: There were 149 patients with TETs and 93 patients with lymphomas enrolled. These patients were assigned to a training set (n = 171) and an external validation set (n = 71). Dedicated radiomics prototype software was used to segment lesions on preoperative chest enhanced CT images and extract features. The multivariable logistic regression algorithm was used to construct three models according to clinico-radiologic features, radiomics features, and combined features, respectively. Performance of the three models was compared by using the area under the receiver operating characteristic curves (AUCs). Decision curve analysis was used to evaluate clinical utility of the three models. Results: For clinico-radiologic model, radiomics signature model, and combined model, the AUCs were 0.860, 0.965, 0.975 and 0.843, 0.961, 0.955 in the training cohort and the test cohort, respectively (all P<0.05). The accuracies of each model were 0.836, 0.895, 0.918 and 0.845, 0.901, 0.859 in the two cohorts, respectively (all P<0.05). Compared with the clinico-radiologic model, better diagnostic performances were found in the radiomics signature model and the combined model. Conclusions: Radiomics signature model and combined model exhibit outstanding and comparable differential diagnostic performances between TETs and lymphomas. The CT-based radiomics analysis might serve as an effective tool for accurately differentiating TETs from lymphomas before treatment.

Computed tomography-based radiomics for predicting lymphovascular invasion in rectal cancer.

PURPOSE: To develop and externally validate a computed tomography (CT)-based radiomics model for predicting lymphovascular invasion (LVI) before treatment in patients with rectal cancer (RC). METHOD: This retrospective study enrolled 351 patients with RC from three hospitals between March 2018 and March 2021. These patients were assigned to one of the following three groups: training set (n = 239, from hospital 1), internal validation set (n = 60, from hospital 1), and external validation set (n = 52, from hospitals 2 and 3). Large amounts of radiomics features were extracted from the intratumoral and peritumoral regions in the portal venous phase contrast-enhanced CT images. The score of radiomics features (Rad-score) was calculated by performing logistic regression analysis following the L1-based method. A combined model (Rad-score + clinical factors) was developed in the training cohort and validated internally and externally. The models were compared using the area under the receiver operating characteristic curve (AUC). RESULTS: Of the 351 patients, 106 (30.2%) had an LVI + tumor. Rad-score (comprised of 22 features) was significantly higher in the LVI + group than in the LVI- group (0.60 ± 0.17 vs. 0.42 ± 0.19, P = 0.001). The combined model obtained good predictive performance in the training cohort (AUC = 0.813 [95% CI: 0.758-0.861]), with robust results in internal and external validations (AUC = 0.843 [95% CI: 0.726-0.924] and 0.807 [95% CI: 0.674-0.903]). CONCLUSIONS: The proposed combined model demonstrated the potential to predict LVI preoperatively in patients with RC.

Computed Tomography-Based Radiomics for Preoperative Prediction of Tumor Deposits in Rectal Cancer.

OBJECTIVE: To develop and validate a computed tomography (CT)-based radiomics model for predicting tumor deposits (TDs) preoperatively in patients with rectal cancer (RC). METHODS: This retrospective study enrolled 254 patients with pathologically confirmed RC between December 2017 and December 2019. Patients were divided into a training set (n = 203) and a validation set (n = 51). A large number of radiomics features were extracted from the portal venous phase images of CT. After selecting features with L1-based method, we established Rad-score by using the logistic regression analysis. Furthermore, a combined model incorporating Rad-score and clinical factors was developed and visualized as the nomogram. The models were evaluated by the receiver operating characteristic curve (ROC) analysis and area under the ROC curve (AUC). RESULTS: One hundred and seventeen of 254 patients were eventually found to be TDs+. Rad-score and clinical factors including carbohydrate antigen (CA) 19-9, CT-reported T stage (cT), and CT-reported peritumoral nodules (+/-) were significantly different between the TDs+ and TDs- groups (all P < 0.001). These factors were all included in the combined model by the logistic regression analysis (odds ratio = 2.378 for Rad-score, 2.253 for CA19-9, 2.281 for cT, and 4.485 for peritumoral nodules). This model showed good performance to predict TDs in the training and validation cohorts (AUC = 0.830 and 0.832, respectively). Furthermore, the combined model outperformed the clinical model incorporating CA19-9, cT, and peritumoral nodules (+/-) in both training and validation cohorts for predicting TDs preoperatively (AUC = 0.773 and 0.718, P = 0.008 and 0.039). CONCLUSIONS: The combined model incorporating Rad-score and clinical factors could provide a preoperative prediction of TDs and help clinicians guide individualized treatment for RC patients.

Radiomics for predicting perineural invasion status in rectal cancer.

BACKGROUND: Perineural invasion (PNI), as a key pathological feature of tumor spread, has emerged as an independent prognostic factor in patients with rectal cancer (RC). The preoperative stratification of RC patients according to PNI status is beneficial for individualized treatment and improved prognosis. However, the preoperative evaluation of PNI status is still challenging. AIM: To establish a radiomics model for evaluating PNI status preoperatively in RC patients. METHODS: This retrospective study enrolled 303 RC patients in a single institution from March 2018 to October 2019. These patients were classified as the training cohort (n = 242) and validation cohort (n = 61) at a ratio of 8:2. A large number of intra- and peritumoral radiomics features were extracted from portal venous phase images of computed tomography (CT). After deleting redundant features, we tested different feature selection (n = 6) and machine-learning (n = 14) methods to form 84 classifiers. The best performing classifier was then selected to establish Rad-score. Finally, the clinicoradiological model (combined model) was developed by combining Rad-score with clinical factors. These models for predicting PNI were compared using receiver operating characteristic curve (ROC) analysis and area under the ROC curve (AUC). RESULTS: One hundred and forty-four of the 303 patients were eventually found to be PNI-positive. Clinical factors including CT-reported T stage (cT), N stage (cN), and carcinoembryonic antigen (CEA) level were independent risk factors for predicting PNI preoperatively. We established Rad-score by logistic regression analysis after selecting features with the L1-based method. The combined model was developed by combining Rad-score with cT, cN, and CEA. The combined model showed good performance to predict PNI status, with an AUC of 0.828 [95% confidence interval (CI): 0.774-0.873] in the training cohort and 0.801 (95%CI: 0.679-0.892) in the validation cohort. For comparison of the models, the combined model achieved a higher AUC than the clinical model (cT + cN + CEA) achieved (P < 0.001 in the training cohort, and P = 0.045 in the validation cohort). CONCLUSION: The combined model incorporating Rad-score and clinical factors can provide an individualized evaluation of PNI status and help clinicians guide individualized treatment of RC patients.