Association between 25 hydroxyvitamin D and serum uric acid level in the Chinese general population: a cross-sectional study.

BACKGROUD: The relationship between serum uric acid (SUA) and 25-hydroxyvitamin D (25(OH)D) has been variably characterized in existing literature, with inconsistent results regarding its nature and implications in the Chinese population. This study aims to clarify this association, considering the potential impact of vitamin D levels on SUA. METHODS: This cross-sectional study involved 7,086 individuals from the Second Affiliated Hospital of Zhejiang University School of Medicine, screened throughout 2020. We collected data on 25(OH)D, SUA, and other metabolic markers. Logistic regression models adjusted for confounding factors were utilized to analyze the relationships. RESULTS: Our findings illustrate a statistically significant inverted U-shaped relationship between 25(OH)D and SUA. The identified threshold effect at 28.82 ng/ml is pivotal; with 25(OH)D levels below this point associated with an increased risk of hyperuricemia (odds ratio: 1.0146, p = 0.0148), and levels above it offering protective benefits (odds ratio: 0.9616, p = 0.0164). CONCLUSIONS: Our findings confirm a nonlinear, inverted U-shaped correlation between 25(OH)D and SUA, emphasizing the importance of maintaining vitamin D levels within a specific range to effectively manage hyperuricemia. These results support the implementation of personalized vitamin D supplementation strategies to optimize metabolic health outcomes, highlighting the complex interplay between vitamin D status and uric acid levels.

Characteristics of sodium and water retention in rats with nephrotic syndrome induced by puromycin aminonucleoside.

INTRODUCTION: Nephrotic syndrome (NS) is characterized by renal sodium and water retention. The mechanisms are not fully elucidated. METHODS: The NS rat model was established by single intraperitoneal injection of 100 mg/kg puromycin aminonucleoside (PAN). The plasma electrolyte level and urinary sodium excretion were monitored dynamically. The changes of some sodium transporters, including epithelial Na+ channel (ENaC), Na+/H+ exchanger 3 (NHE3), Na+-K+-2Cl- cotransporter 2 (NKCC2) and Na+-Cl- cotransporter (NCC) in renal cortex at different time points and the level of peripheral circulation factors were detected. RESULTS: The urinary sodium excretion of the model group increased significantly on the first day, then decreased compared with the control group, and there was no significant difference between the model group and the control group on the 12th day. The changes of peripheral circulation factors were not obvious. Some sodium transporters in renal cortex increased in varying degrees, while NKCC2 decreased significantly compared with the control group. CONCLUSIONS: The occurrence of NS edema may not be related to the angiotensin system. The decrease of urinary sodium excretion is independent of the development of albuminuria. During the 18 days of observation, it can be divided into three stages: sodium retention, sodium compensation, and simple water retention. The mechanism is related to the increased expression of α-ENaC, γ-ENaC, NHE3 and NCC in a certain period of time, the compensatory decrease of NKCC2 expression and the continuous increase of aquaporin 2 (AQP2) expression.

[A fusion network model based on limited training samples for the automatic segmentation of pelvic endangered organs].

When applying deep learning to the automatic segmentation of organs at risk in medical images, we combine two network models of Dense Net and V-Net to develop a Dense V-network for automatic segmentation of three-dimensional computed tomography (CT) images, in order to solve the problems of degradation and gradient disappearance of three-dimensional convolutional neural networks optimization as training samples are insufficient. This algorithm is applied to the delineation of pelvic endangered organs and we take three representative evaluation parameters to quantitatively evaluate the segmentation effect. The clinical result showed that the Dice similarity coefficient values of the bladder, small intestine, rectum, femoral head and spinal cord were all above 0.87 (average was 0.9); Jaccard distance of these were within 2.3 (average was 0.18). Except for the small intestine, the Hausdorff distance of other organs were less than 0.9 cm (average was 0.62 cm). The Dense V-Network has been proven to achieve the accurate segmentation of pelvic endangered organs.

Dosimetric comparison of three intensity-modulated radiation therapies for left breast cancer after breast-conserving surgery.

PURPOSE: This study aimed to evaluate dosimetric differences of intensity-modulated radiation therapy (IMRT) in target and normal tissues after breast-conserving surgery. METHODS: IMRT five-field plan I, IMRT six-field plan II, and field-in-field-direct machine parameter optimization-IMRT plan III were designed for each of the 50 patients. One-way analysis of variance was performed to compare differences, and P < 0.05 was considered statistically significant. RESULTS: Homogeneity index of plan III is lower than those of plans I and II. No difference was identified in conformity index of targets. Plan I exhibited difference in mean dose (Dmean ) for the heart (P < 0.05). Plan I featured smaller irradiation dose volumes in V5 , V20 (P < 0.05) of the left lung than II. Plan I exhibited significantly higher V5 in the right lung than plans II and III (P < 0.05). Under plan I, irradiation dose at V5 in the right breast is higher than that in plans II and III. Patients in plan III presented less total monitor unit and total treatment time than those in plans I and II (P < 0.05). CONCLUSION: IMRT six-field plans II, and field-in-field-direct machine parameter optimization-IMRT plans III can reduce doses and volumes to the lungs and heart better while maintaining satisfying conformity index and homogeneity index of target. Nevertheless, plan II neglects target movements caused by respiration. In the same manner, plan III can substantially reduce MU and shorten patient treatment time. Therefore, plan III, which considers target movement caused by respiration, is a more practical radiation mode.

[A preliminary study on origin of ligustrazine in Chuanxiong Rhizoma based on endogenetic Bacillus subtilis].

Ligustrazine is an important active ingredient of the traditional Chinese medicine Chuanxiong Rhizoma, but its content is a controversial topic. The endophytes of medicinal plants have the ability to produce the same active substances as the host, so this report focused on the endophytic Bacillus subtilis, to study the origin of ligustrazine in Chuanxiong Rhizoma preliminarily by inoculating the isolated endophytic B. subtilis to the Chuanxiong Rhizoma medium in vitro for solid state fermentation. Tissue grinding method was used to isolate the endogenetic B. subtilis. The morphological features, conventional physiological and biochemical reactions and 16S rRNA molecular techniques were combined to identify the endogenetic strains. Then, the strains that grew well in the medicinal matrix of Chuanxiong Rhizoma were screened out for further fermentation studies. The solid-state fermentation was performed at 37 °C for 30 d using Chuanxiong Rhizoma fermentation medium (40 g Chuanxiong Rhizoma powder, 100 mL sterile water, 121 °C, sterilization for 25 minutes). UPLC was used to detect the contents of ligustrazine, acetoin in the Chuanxiong Rhizoma fermentation medium and Chuanxiong Rhizoma. All the five strains were Gram-positive and had spores. Phylogenetic analysis of the 16S rRNA sequence showed that the endophytes were B. subtilis. The results of UPLC showed that ligustrazine was detected in the Chuanxiong Rhizoma fermentation medium inoculated with endogenetic B. subtilis LB3, LB3-2-1, LB4, LB5 and LB6-2, while not detected neither in blank Chuanxiong Rhizoma fermentation medium nor in Chuanxiong Rhizoma. This study showed that the endogenetic B. subtilis of Ligusticum chuanxiong Hort. can make use of Chuanxiong Rhizoma fermentation medium to produce ligustrazine. Endogenetic B. subtilis has a certain correlation with the accumulation of ligustrazine in Rhizoma Chuanxiong. We speculate that the ligustrazine may be derived from the catabolism of endogenetic B. subtilis in Ligusticum chuanxiong.

The difference between blood-associated and water-associated herbs of Danggui-Shaoyao San in theory of TCM, based on serum pharmacochemistry.

Danggui-Shaoyao San (DSS) is a famous Chinese formula for activating blood circulation and promoting urination. This study was to investigate the difference of material basis between a blood-associated herbs group and a water-associated herbs group. According to the theory of traditional Chinese medicine, the formula can be divided into a blood-associated herbs group (Angelica sinensis, Paeonia lactiflora and Ligusticum chuanxiong) and a water-associated herbs group (Atractylodes macrocephala, Alisma orientale and Poria cocos). The HPLC fingerprint of the formula was established for quality control. Serum samples from rats, orally administrated DSS, and the decomposed recipes of DSS, were analyzed by HPLC-DAD and the transitional blood components of DSS were identified. Twenty-one common peaks were identified in the fingerprint of DSS. Contents of paeoniflorin, albiflorin, ferulic acid and alisol B 23-acetate in co-decoction were significantly higher than those in individual decoction. Eleven peaks belonged to the blood-associated herbs group (four metabolites and seven prototype components; paeoniflorin and ferulic acid appeared in prototype components), whereas six peaks belonged to the water-associated herbs group (three metabolites and three prototype components). It was concluded that the serum pharmacochemistry is a meaningful approach for clarifying the difference between blood-associated and water-associated herbs in chemical composition.

[Mechanism Study on Danggui Shaoyao San and Guizhi Fuling Wan For Treating Primary Dysmenorrheal Based on Biological Network].

OBJECTIVE: To investigate the molecular mechanisms of Danggui Shaoyao San and Guizhi Fuling Wan for treating primary dysmenorrhea of liver depression and blood stasis syndrome by biological network method. METHODS: Targets of the formula were collected from. PubMed database, and targets of primary dysmenorrhea were searched from Gene Card database. Then, the "formula-syndromes-disease" network was constructed and analyzed with Cytoscape software. Molecular docking approach was used to verify estrogen-like effect of ingredients. RESULTS: The "formula-syndromes-disease" shared multiple targets, which involves a variety of important nodes, such as IL and PGF2α, and played the effects of anti-inflammatory and analgesic. Danggui Shaoyao San could influence the function of hormones, such as corticotropin releasing hormone, and inhibit hyperactivity of adrenal axis. Guizhi Fuling Wan mainly affected a series of inflammation caused by cyclooxygenase and had the effects of blood coagulation. Estrogen-like effect of Danggui Shaoyao Sanwas stronger than that of Guizhi Fuling Wan. CONCLUSION: The novel approach will present an effective strategy for theory study of Danggui Shaoyao San and Guizhi Fuling Wan for treating primary dysmenorrhea.

[The Dose Effect of Isocenter Selection during IMRT Dose Verification with the 2D Chamber Array].

To investigate the dose effect of isocenter difference during IMRT dose verification with the 2D chamber array. The samples collected from 10 patients were respectively designed for IMRT plans, the isocenter of which was independently defined as P(o), P(x) and P(y). P(o) was fixed on the target center and the other points shifted 8cm from the target center in the orientation of x/y. The PTW729 was used for 2D dose verification in the 3 groups which beams of plans were set to 0 degrees. The γ-analysis passing rates for the whole plan and each beam were gotten using the different standards in the 3 groups, The results showed the mean passing rate of γ-analysis was highest in the P(o) group, and the mean passing rate of the whole plan was better than that of each beam. In addition, it became worse with the increase of dose leakage between the leaves in P(y) group. Therefore, the determination of isocenter has a visible effect for IMRT dose verification of the 2D chamber array, The isocenter of the planning design should be close to the geometric center of target.

Enhancement of radiosensitivity by 5-Aza-CdR through activation of G2/M checkpoint response and apoptosis in osteosarcoma cells.

Radiation resistance is a major problem preventing successful treatment. Therefore, identifying sensitizers is vitally important for radiotherapy success. Epigenetic events such as DNA methylation have been proposed to mediate the sensitivity of tumor therapy. In this study, we investigated the influence of demethylating agent 5-Aza-2'-deoxycytidine (5-Aza-CdR) on the radiosensitivity of human osteosarcoma cell lines. 5-Aza-CdR was capable of sensitizing three osteosarcoma cells to irradiation in a time-dependent manner, with the maximum effect attained by 48 h. Pretreatment with 5-Aza-CdR synchronized cells in G2/M phase of the cell cycle and enhanced irradiation-induced apoptosis compared with irradiation alone in SaOS2, HOS, and U2OS cells. Moreover, 5-Aza-CdR restored mRNA expressions of 14-3-3σ, CHK2, and DAPK-1 in the three cells, accompanied with demethylation of their promoters. These findings demonstrate that demethylation with 5-Aza-CdR increases radiosensitivity in some osteosarcoma cells through arresting cells at G2/M phase and increasing apoptosis, which is partly mediated by upregulation of 14-3-3σ, CHK2, and DAPK-1 genes, suggesting that 5-Aza-CdR may be a potential radiosensitizer to improve the therapy effect in osteosarcoma.

[Dosimetric calibration of CT pencil chamber in cobalt beams].

OBJECTIVE: To explore the dose-length product calibration method for pencil ionization chamber in cobalt beams. METHODS: The PTW TM30009 ionization chamber was placed into the central hole of T40017 head phantom and irradiated 60 s in 20 cm x 20 cm cobalt beam. The charge was collected with UNIDOS electrometer. Absorbed doses were measured with TM30013 0.6 mL farmer-type chamber under the same condition. The CT chamber calibration factor was expressed in dose-length product. Dose linearity and spatial response were also investigated. RESULTS: The calibration factor in dose-length product was derived from measured data. Dose linearity and spatial response were good in cobalt beams. CONCLUSION: It is feasible to calibrate the CT chamber in cobalt beams for patient dose evaluation in MVCT.

[Use of megavoltage CT(MVCT) in helical tomotherapy for head and neck dose calculation].

OBJECTIVE: To evaluate the feasibility and accuracy of using Megavoltage CT(MVCT) for head and neck dose calculation. METHODS: The cheese Phantom was imaged using MVCT scanner, and the MVCT value density calibration curve was established. Conventional CT and MVCT image of nasopharyngeal carcinoma was acquired respectively, and IMRT plan was designed on conventional CT image of NPC patient. The conventional CT plan was copied to MVCT image. The dose distribution was calculated for tumor and normal tissue using the MVCT value density calibration curve, and compared with that of conventional CT. Ten NPC patients were collected for dose verification of IMRT plan on MVCT images. RESULTS: The MVCT numbers depended linearly on the electron density of the sample, and the stability of the MVCT numbers to electron density was good.The error between the measured dose and calculated dose in measured point was less than 3%.The isodose distribution was well agreement with that calculated by planning system. CONCLUSIONS: Performing dose recalculation using MVCT of Tomotherapy in head and neck region was feasible.and the dose distributions on kVCT and MVCT were in excellent agreement.

Combined analysis of bulk RNA and single-cell RNA sequencing to identify pyroptosis-related markers and the role of dendritic cells in chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease (COPD) is characterized by dyspnea caused by airflow limitation. Further development may lead to decreased lung function and other lung diseases. Pyroptosis is a type of programmed cell death that involves multiple pathways. For example, the pathway induced by the NLR family pyrin domain containing 3 (NLRP3) inflammasome is closely associated with COPD exacerbation. Therefore, in this study, various machine learning algorithms were applied to screen for diagnostically relevant pyroptosis-related genes from the GEO dataset, and the results were verified using external datasets. The results showed that deep neural networks and logistic regression algorithms had the highest AUC of 0.91 and 0.74 in the internal and external test sets, respectively. Here, we explored the immune landscape of COPD using diagnosis-related genes. We found that the infiltrating abundance of dendritic cells significantly differed between the COPD and control groups. Finally, the communication patterns of each cell type were explored based on scRNA-seq data. The critical role of significant pathways involved in communication between DCS and other cell populations in the occurrence and progression of COPD was identified.

Network pharmacology mechanisms and experimental verification of licorice in the treatment of ulcerative colitis.

ETHNOPHARMACOLOGICAL RELEVANCE: Licorice is widely used in the treatment of ulcerative colitis (UC) and has good antioxidant and anti-inflammatory effects, but its specific active ingredients and mechanisms of action are still unknown. THE PURPOSE OF THE STUDY: To elucidate the specific molecular mechanisms of licorice in the treatment of UC and to experimentally verify its activity. METHODS: Through network pharmacology, the active ingredients of licorice and the molecular targets of UC were identified. A traditional Chinese medicine (TCM)-components-target-disease network diagram was established, and the binding energies of the active ingredient and targets of licorice were verified by molecular docking. A BALB/c mice model of UC was established by treatment with 3% dextran sulfate sodium (DSS). The effect of licorice on colon tissue injury was histologically assessed. The expression of IL-6 and IL-17 in colon tissue was detected by immunohistochemistry (IHC). Transmission electron microscopy (TEM) was used to observe morphological changes in mitochondria in the colon. Caco2 cells were treated with lipopolysaccharide (LPS) for 24 h to establish the cell inflammatory damage model, and cells were exposed to different concentrations of drug-containing serum of Licorice (DCSL) for 24 h. In cells treated with the drug, the contents of oxidation markers were measured and ELISA was used to determine the levels of inflammatory factors in the cells. TEM was used to observe morphological changes in mitochondria. ZO-1 and occludin were detected by Western blotting. DCSL effects on autophagy were evaluated by treating cells with DCSL and autophagy inhibitor for 24 h after LPS injection. Small interfering ribonucleic acid (si-RNA) was used to silence Nrf2 gene expression in Caco2 cells to observe the effects of DCSL on autophagy through the Nrf2/PINK1 pathway. Nrf2, PINK1, HO-1, Parkin, P62, and LC3 were detected by Western blotting. RESULTS: Ninety-one active ingredients and 339 action targets and 792 UC disease targets were identified, 99 of which were overlapping targets. Molecular docking was used to analyze the binding energies of liquiritin, liquiritigenin, glycyrrhizic acid, and glycyrrhetinic acid to the targets, with glycyrrhetinic acid having the strongest binding energy. In the UC mouse model, licorice improved colon histopathological changes, reduced levels of IL-6 and IL-17 and repaired mitochondrial damage. In the LPS-induced inflammation model of Caco2 cells, DCSL decreased MDA, IL-1ß, Il-6, and TNF-α levels and increased those of Superoxide Dismutase (SOD), glutathione peroxidase (GSH-PX), and IL-10, and improved the morphological changes of mitochondria. Increased expression of Nrf2, PINK1, Parkin, HO-1, ZO-1, occludin, P62, and LC3 promoted autophagy and reduced inflammation levels. CONCLUSION: Licorice improves UC, which may be related to the activation of the Nrf2/PINK1 signaling pathway that regulates autophagy.

Human-like acceleration and deceleration control of a robot astronaut floating in a space station.

The acceleration and deceleration (AD) motions are the basic motion modes of robot astronauts moving in a space station. Controlling the locomotion of the robot astronaut is very challenging due to the strong nonlinearity of its complex multi-body dynamics in a gravity-free environment. However, after training, humans can move well in space stations by pushing the bulkhead, and the motion mechanism of humans is a good reference for robot astronauts. The contribution of this study is modeling the human AD motion in a microgravity environment and proposing a human-like control method for robot astronauts moving in space stations. Specifically, the movement and contact force data of the human body during AD motion were collected on an air-floating platform. Through human AD modeling analysis, the mechanism of human motion is discovered, and semi-sinusoidal primitives of contact forces are proposed for AD motion. Then, a dynamic guidance model of human AD motion is built to complete motion planning under contact constraints, which is used as the expected model for the AD control of robot astronauts. Benefiting from the force primitives, accurate and safe planning of human-like AD motion can be completed. The characteristics and mechanism of human AD motion have been analyzed from the perspective of optimization. Lastly, based on the proposed dynamic guidance model, the AD motion policy is mapped to the robot astronaut system via a system control method based on the equivalent mapping of dynamic responses (force, velocity and pose). Through comparative analysis with real human motion data and simulation results under different conditions, the proposed AD control method can achieve human-like motion efficiently and stably. Even when confronted with errors in the robot's contact velocities and inertia parameters, the method can significantly reduce the motion errors while ensuring stability.

[Verification of the couch automatic movement accuracy for Hi-ART tomotherapy].

The QUASAR Penta-guide Phantom with fiducial markers was scanned, and the CT images were transferred to Pinnacle workstation. Skin and target volumes were contoured and transferred to TomoPlan treatment planning system. The phantom was scanned with Megavoltage CT (MVCT). MVCT images were matched to the planning CT. Automatic adjustment of treatment couch was completed. It was found that the green laser coincided with the etched center crosshairs in lateral and longitudinal directions with an error less than 2 mm. However 2 mm vertical tabletop lag was found, but could be eventually corrected. Verifications for specific patients with head and pelvic tumors were also completed, the residual setup error were analyzed. The automatic movement of tabletop after image match is satisfactory.

Licorice protects against ulcerative colitis via the Nrf2/PINK1-mediated mitochondrial autophagy.

PURPOSE: Study of the effects and mechanisms of licorice in the treatment of ulcerative colitis (UC) from the perspective of mitochondrial autophagy. METHODS: BALB/C mice were induced with 3% dextran sodium sulfate to build an animal model of UC. After 7 days of modeling, different doses of licorice were administered for 7 days. Hematoxylin and eosin staining is used to detect pathological changes in the colon. Mitochondrial membrane potentials and reactive oxygen species (ROS) contents were detected by flow cytometry, and autophagy of mitochondria was observed by transmission electron microscopy. Determination of inflammatory cytokines by enzyme-linked immunosorbent assay. The oxidizing factors are detected by the kits. Western blot analysis was used to detect expressions for nuclear factor called erythropoietin (Nrf2), pten-induced protein kinase 1 (PINK1), Parkin, HO-1, P62, and LC3. RESULTS: Licorice improved the pathological condition of UC mice, increasing the mitochondrial membrane potential and decreasing the ROS content. Promotes the emergence of autophagosomes and autophagosomes. The contents of interleukin (IL)-1ß, IL-6, IL-17, and tumor necrosis factor-alpha were downregulated, the contents of superoxide dismutase and glutathione peroxidase were upregulated and the contents of malondialdehyde were downregulated. In addition, licorice promotes the expression of Nrf2, PINK1, Parkin, HO-1, P62, and LC3. CONCLUSION: Licorice was shown to reduce levels of inflammatory factors and oxidative stress in mice with UC, possibly by promoting mitochondrial autophagy through the activation of the Nrf2/PINK1 pathway.

Sini San ameliorates CCl4-induced liver fibrosis in mice by inhibiting AKT-mediated hepatocyte apoptosis.

ETHNOPHARMACOLOGICAL RELEVANCE: Sini San (SNS) is recorded in Zhang Zhongjing's "Treatise on Typhoids" and is used in the treatment of non-alcoholic fatty liver disease, hepatitis, and other liver diseases, with good efficacy in liver fibrosis. However, its anti-liver fibrosis mechanism remains unclear. AIM OF THE STUDY: This study aimed to evaluate the ameliorative effect of SNS on carbon tetrachloride (CCl4)-induced liver fibrosis in mice and the underlying mechanisms. MATERIALS AND METHODS: The active ingredients in the water extract of SNS were determined using high-performance liquid chromatography (HPLC). CCl4-induced liver fibrosis mice were subsequently treated with different doses of SNS for 3 weeks, and AST, ALT, and T-BIL were detected in the serum. The pathological characteristics of the liver were observed using hematoxylin and eosin (H&E) and Masson's staining. Hepatocyte apoptosis was assessed using terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining. The proteins expression of PI3K, p-PI3K, AKT, p-AKT, FXR, caspase-8, Bax, and Bcl-2 was analyzed using western blotting and immunofluorescence. FXR mRNA expression was measured using quantitative real-time reverse transcription-polymerase chain reaction (RT-qPCR). Using network pharmacology and bioinformatics to search for active ingredients that regulate PI3K/AKT signaling in the SNS. The material basis for regulating PI3K/AKT signaling in SNS was searched using network pharmacology and bioinformatics. Based on the network pharmacology results, isorhamnetin or SNS-containing serum was added to HepG2 cells stimulated with TNF-α. The Cell Counting Kit (CCK)-8 assay was used to analyze cell viability and apoptosis of HepG2 cells was detected using flow cytometry. RESULTS: SNS reduced serum levels of AST, ALT and T-BIL, down-regulated caspase-8 protein expression and the ratio of Bcl-2/Bax protein expression, and improved apoptosis in liver fibrosis mice. In addition, SNS downregulated the ratio of p-PI3K/PI3K and p-AKT/AKT protein expression and increased FXR expression. Network pharmacology studies showed that quercetin, kaempferol and isorhamnetin in SNS can bind to AKT. In vitro experiments showed that isorhamnetin inhibited HepG2 cell apoptosis, upregulated FXR expression and suppressed AKT activity, whereas AKT inhibitors blocked the effects of isorhamnetin. The effect of the SNS-containing serum was similar to that of isorhamnetin. CONCLUSION: SNS ameliorated the progression of fibrosis and improved hepatocyte apoptosis in liver fibrosis mice. The anti-apoptotic mechanism was related to the inhibition of AKT-mediated down-regulation of FXR expression by its active ingredient, isorhamnetin.

Development and Validation of an Ultrasound-Based Radiomics Nomogram for Identifying HER2 Status in Patients with Breast Carcinoma.

(1) Objective: To evaluate the performance of ultrasound-based radiomics in the preoperative prediction of human epidermal growth factor receptor 2-positive (HER2+) and HER2- breast carcinoma. (2) Methods: Ultrasound images from 309 patients (86 HER2+ cases and 223 HER2- cases) were retrospectively analyzed, of which 216 patients belonged to the training set and 93 patients assigned to the time-independent validation set. The region of interest of the tumors was delineated, and the radiomics features were extracted. Radiomics features underwent dimensionality reduction analyses using the intra-class correlation coefficient (ICC), Mann-Whitney U test, and the least absolute shrinkage and selection operator (LASSO) algorithm. The radiomics score (Rad-score) for each patient was calculated through a linear combination of the nonzero coefficient features. The support vector machine (SVM), K nearest neighbors (KNN), logistic regression (LR), decision tree (DT), random forest (RF), naive Bayes (NB) and XGBoost (XGB) machine learning classifiers were trained to establish prediction models based on the Rad-score. A clinical model based on significant clinical features was also established. In addition, the logistic regression method was used to integrate Rad-score and clinical features to generate the nomogram model. The leave-one-out cross validation (LOOCV) method was used to validate the reliability and stability of the model. (3) Results: Among the seven classifier models, the LR achieved the best performance in the validation set, with an area under the receiver operating characteristic curve (AUC) of 0.786, and was obtained as the Rad-score model, while the RF performed the worst. Tumor size showed a statistical difference between the HER2+ and HER2- groups (p = 0.028). The nomogram model had a slightly higher AUC than the Rad-score model (AUC, 0.788 vs. 0.786), but no statistical difference (Delong test, p = 0.919). The LOOCV method yielded a high median AUC of 0.790 in the validation set. (4) Conclusion: The Rad-score model performs best among the seven classifiers. The nomogram model based on Rad-score and tumor size has slightly better predictive performance than the Rad-score model, and it has the potential to be utilized as a routine modality for preoperatively determining HER2 status in BC patients non-invasively.

Glycyrrhiza uralensis Fisch. alleviates dextran sulfate sodium-induced colitis in mice through inhibiting of NF-κB signaling pathways and modulating intestinal microbiota.

ETHNOPHARMACOLOGICAL RELEVANCE: Licorice is widely used in traditional Chinese Medicine (TCM) for compound compatibility, which could reduce toxicity and increase efficacy of certain herbal medicine, and its active components prominently effects of inhibit of inflammation and regulate of immunity. AIM OF THE STUDY: The study probed into the mechanism of the anti-inflammatory and immunomodulatory effects of licorice based on the domination of the T helper type 17/regulatory T cells (Th17/Treg) differentiation balance and the composition and structure of the intestinal flora through the nuclear factor kappa B (NF-κB) signaling pathway. MATERIALS AND METHODS: BALB/c mice were inoculated with dextran sulfate sodium (DSS) to establish animal models of ulcerative colitis (UC). For the pharmacodynamic study, UC mice were observed for the anti-inflammatory effect of licorice water extraction (LWE) in vivo, including clinical observation and measurement of colon length. Hematoxylin-eosin (HE) staining was used to evaluate pathological conditions. Immunohistochemistry (IHC) and transmission electron microscopy (TEM) were performed to observe the intestinal barrier of the colons. Inflammatory cytokine levels were measured using with enzyme-linked immunosorbent assay (ELISA) kits. The proportions of T helper (Th) cells in the colons was assessed using flow cytometry. Gut microbiota diversity was detected using 16S ribosomal (r)DNA sequencing. In addition, Western blot (WB) assays were used to verify ROR-γt, Foxp3, TLR4, MyD88 and NF-κB expression according to a standard protocol. RESULTS: LWE exerted a pharmacological anti-inflammatory effect by attenuating inflammation in the colonic tissues through affecting the protein expression of TLR4/MyD88/NF-κB, and increasing the expression of tight junction (TJ) protein in the colons, improving the integrity of the intestinal mucosal barrier in vivo. Moreover, LWE reversed the imbalance in Th17/Treg cells differentiation and influenced the protein expression of ROR-γt and Foxp3 in UC mouse colons. In particular, LWE significantly affected the diversity of the gut microbiota in UC mice, ameliorated the composition of dominant species, and significantly increased the type and quantity of probiotics. CONCLUSION: Licorice tends to reduce inflammation and enhance the protective action of the intestinal mucosal barrier via the TLR4/MyD88/NF-κB signal transduction pathway and alter the imbalance of Th-cell differentiation. Notably, licorice may affect the diversity of intestinal microbiota and the content of beneficial bacteria in the colon, which is a potential mechanism for understanding anti-inflammatory and immunomodulatory effects in UC mice in vivo.

Development and validation of an ultrasound-based radiomics nomogram for predicting the luminal from non-luminal type in patients with breast carcinoma.

Introduction: The molecular subtype plays a significant role in breast carcinoma (BC), which is the main indicator to guide treatment and is closely associated with prognosis. The aim of this study was to investigate the feasibility and efficacy of an ultrasound-based radiomics nomogram in preoperatively discriminating the luminal from non-luminal type in patients with BC. Methods: A total of 264 BC patients who underwent routine ultrasound examination were enrolled in this study, of which 184 patients belonged to the training set and 80 patients to the test set. Breast tumors were delineated manually on the ultrasound images and then radiomics features were extracted. In the training set, the T test and least absolute shrinkage and selection operator (LASSO) were used for selecting features, and the radiomics score (Rad-score) for each patient was calculated. Based on the clinical risk features, Rad-score, and combined clinical risk features and Rad-score, three models were established, respectively. The performances of the models were validated with receiver operator characteristic (ROC) curve and decision curve analysis. Results: In all, 788 radiomics features per case were obtained from the ultrasound images. Through radiomics feature selection, 11 features were selected to constitute the Rad-score. The area under the ROC curve (AUC) of the Rad-score for predicting the luminal type was 0.828 in the training set and 0.786 in the test set. The nomogram comprising the Rad-score and US-reported tumor size showed AUCs of the training and test sets were 0.832 and 0.767, respectively, which were significantly higher than the AUCs of the clinical model in the training and test sets (0.691 and 0.526, respectively). However, there was no significant difference in predictive performance between the Rad-score and nomogram. Conclusion: Both the Rad-score and nomogram can be applied as useful, noninvasive tools for preoperatively discriminating the luminal from non-luminal type in patients with BC. Furthermore, this study might provide a novel technique to evaluate molecular subtypes of BC.