Dihydromyricetin ameliorates experimental ulcerative colitis by inhibiting neutrophil extracellular traps formation via the HIF-1α/VEGFA signaling pathway.

Dihydromyricetin (DHM), which has various biological functions, possesses therapeutic potential for ulcerative colitis (UC). Neutrophil extracellular traps (NETs) and their components play a crucial role in several pathological processes in UC. However, whether DHM alleviates UC by regulating NETs remains unclear. Mice with dextran sulfate sodium (DSS)-induced acute colitis were treated with DHM at different concentrations, and the severity of colitis was evaluated by assessing body weight, colon length, histological scores, cytokine production, and epithelial barrier integrity. To quantify and visualize NETs, the expression of cell free-DNA (cf-DNA) in serum and Cit-H3 in colonic tissue was analyzed via western blotting and immunofluorescence analysis. HL-60 cells and mouse bone marrow-derived neutrophils (BMDNs) were used to evaluate the effects of DHM on NETs in vitro. NETs were treated with DHM at varying concentrations or DNase I and used to repair the intestinal epithelial barrier in a Caco-2/HIEC-6 cell monolayer model. Furthermore, the genes targeted by DHM through neutrophils for alleviating UC were identified by screening online databases, and the results of network pharmacological analysis were verified via western blotting and quantitative real-time polymerase chain reaction. DHM alleviated DSS-induced colitis in mice by reversing weight loss, increased DAI score, colon length shortening, enhanced spleen index, colonic pathological damage, cytokine production, and epithelial barrier loss in a dose-dependent manner. In addition, it inhibited the formation of NETs both in vivo and in vitro. Based on the results of network pharmacological analysis, DHM may target HIF-1α and VEGFA through neutrophils to alleviate UC. Treatment with PMA increased the expression of HIF-1α and VEGFA in D-HL-60 cells and BMDNs, whereas treatment with DHM or DNase I reversed this effect. Treatment with DMOG, an inhibitor of HIF prolyl hydroxylase (HIF-PH), counteracted the suppressive effects of DHM on NETs formation in D-HL-60 cells and BMDNs. Accordingly, it partially counteracted the protective effects of DHM on the intestinal epithelial barrier in Caco-2 and HIEC-6 cells. These results indicated that DHM alleviated DSS-induced UC by regulating NETs formation via the HIF-1α/VEGFA signaling pathway, suggesting that DHM is a promising therapeutic candidate for UC.

Endoscopic Bilateral Nipple-sparing Mastectomy via a Single Axillary Incision with Immediate Pre-pectoral Implant-based Breast Reconstruction.

Oncoplastic breast surgery, with its focus on improving cosmetic outcomes while maintaining oncological safety, has fundamentally transformed the landscape of breast cancer surgical treatment, giving rise to an array of techniques for breast reconstruction. Nipple-sparing mastectomy (NSM) with immediate implant-based breast reconstruction (IBBR) has emerged as a cornerstone in managing early breast cancer. Aligned with the principles of minimally invasive surgery, recent years have witnessed the widespread integration of endoscopic approaches in breast surgery, encompassing procedures like endoscopic breast-conserving surgery (E-BCS) and endoscopic nipple-sparing mastectomy (E-NSM), among others. Capitalizing on the advantages of inconspicuous and shorter incisions, improved visibility, and the avoidance of radiation therapy, the popularity of E-NSM with IBBR is on the rise. However, conventional E-NSM with IBBR often requires two or more incisions, which can result in suboptimal cosmetic outcomes and even prosthesis loss.This paper presents a comprehensive account of the intricate surgical procedures involved in endoscopic bilateral nipple-sparing mastectomy with immediate pre-pectoral implant-based breast reconstruction. The insights shared are drawn from the collective experience of our institution. Notable benefits associated with the described surgical approach encompass enhanced cosmetic outcomes, improved postoperative quality of life, and enhanced physiological functions attributable to the application of pre-pectoral implant-based breast reconstruction through a single incision.

Nets in fibrosis: Bridging innate immunity and tissue remodeling.

Fibrosis, a complex pathological process characterized by excessive deposition of extracellular matrix components, leads to tissue scarring and dysfunction. Emerging evidence suggests that neutrophil extracellular traps (NETs), composed of DNA, histones, and antimicrobial proteins, significantly contribute to fibrotic diseases pathogenesis. This review summarizes the process of NETs production, molecular mechanisms, and related diseases, and outlines the cellular and molecular mechanisms associated with fibrosis. Subsequently, this review comprehensively summarizes the current understanding of the intricate interplay between NETs and fibrosis across various organs, including the lung, liver, kidney, skin, and heart. The mechanisms by which NETs contribute to fibrogenesis, including their ability to promote inflammation, induce epithelial-mesenchymal transition (EMT), activate fibroblasts, deposit extracellular matrix (ECM) components, and trigger TLR4 signaling were explored. This review aimed to provide insights into the complex relationship between NETs and fibrosis via a comprehensive analysis of existing reports, offering novel perspectives for future research and therapeutic interventions.

Identification of a Rye Spring Mutant Derived from a Winter Rye Variety by High-Altitude Environment Screening Using RNA Sequencing Technology.

Wintergrazer-70 and Ganyin No1 are high-yield forage varieties suitable for cultivation in high-altitude areas of Tibet (4300 m above sea level). Ganyin No1 was developed from Wintergrazer-70, with the latter serving as its parent variety. Ganyin No1 was identified as a spring variety, and subsequent RNA sequencing was conducted. RNA sequencing analysis identified 4 differentially expressed genes related to vernalization and 28 genes related to photoperiod regulation. The Sc7296g5-i1G3 gene is related to the flowering inhibition of rye, which may be related to the phenotypic difference in the Ganyin No1 variety in winter and spring. This finding provides valuable insights for future research on Ganyin No1, especially in addressing feed shortages in Tibet during winter and spring.

Mechanistic insights into targeting caspase-3 activation and alveolar macrophage pyroptosis by Ephedra and bitter almond compounds for treating pediatric pneumonia via network pharmacology and bioinformatics.

This study investigates the molecular mechanism of Ma Huang-Ku Xing Ren, a traditional Chinese medicine formula, in treating pediatric pneumonia. The focus is on the regulation of caspase-3 activation and reduction of alveolar macrophage necrosis through network pharmacology and bioinformatics analyses of Ephedra and bitter almond components. Active compounds and targets from ephedrine and bitter almond were obtained using TCMSP, TCMID, and GeneCards databases, identifying pediatric pneumonia-related genes. A protein-protein interaction (PPI) network was constructed, and core targets were screened. GO and KEGG pathway enrichment analyses identified relevant genes and pathways. An acute pneumonia mouse model was created using the lipopolysaccharide (LPS) inhalation method, with caspase-3 overexpression induced by a lentivirus. The mice were treated with Ephedra and bitter almond through gastric lavage. Lung tissue damage, inflammatory markers (IL-18 and IL-1ß), and cell death-related gene activation were assessed through H&E staining, ELISA, western blot, flow cytometry, and immunofluorescence. The study identified 128 active compounds and 121 gene targets from Ephedra and bitter almond. The PPI network revealed 13 core proteins, and pathway analysis indicated involvement in inflammation, apoptosis, and cell necrosis, particularly the caspase-3 pathway. In vivo results showed that Ephedra and bitter almond treatment significantly mitigated LPS-induced lung injury in mice, reducing lung injury scores and inflammatory marker levels. It also decreased caspase-3 activity and cell death in alveolar macrophages. In conclusion, the active ingredients of Ma Huang-Ku Xing Ren, particularly targeting caspase-3, may effectively treat pediatric pneumonia by reducing apoptosis in alveolar macrophages, as demonstrated by both network pharmacology, bioinformatics analyses, and experimental data.

YiQi GuBen capsule alleviates OVA-induced asthma through improving mitochondrial dysfunction.

Objective: This study aims to explore the effect of YiQi GuBen capsule on improving mitochondrial dysfunction in an animal model of asthma.Methods: The mice (n = 8) were divided into four groups including control (NC), ovalbumin (OVA), dexamethasone (OVA + DEX), and YiQi GuBen (OVA + YQGB) groups. Firstly, we established an OVA-induced mouse asthma model except for the NC group, which then were treated with dexamethasone and YiQi GuBen capsule. Subsequently, HE staining and Masson staining were used for pathological analysis of mice lung tissues. Next, we used transmission electron microscopy (TEM) to observe the effect of the Yiqi Guben capsule on the ultrastructure of mitochondria. Flow cytometry was used to analyze the ROS level, membrane potential, and the number of mitochondria in lung tissue. Moreover, we analyzed the copy number of mitochondrial DNA (mtDNA) and the expression levels of activator peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) and mitochondrial transcription factor A (TFAM).Results: The results of the pathological analysis showed that after treatment with the YiQi GuBen capsule, the lung tissue damage was significantly reduced. In addition, we observed that the ultrastructural damage of mitochondria was improved. Flow cytometry proved that after treatment with the YiQi GuBen capsule, the level of ROS in the mitochondria was effectively reduced, while the mitochondrial membrane potential decreased and the number increased significantly. Moreover, we found that the copy number of mtDNA was significantly increased and the expression levels of PGC-1α and TFAM were significantly upgraded.Conclusion: This study suggests YiQi GuBen capsule can effectively improve mitochondrial dysfunction in the OVA-induced mouse model.

A meta-analysis of the effects of vitamin C supplementation for pregnant smokers on the pulmonary function of their offspring.

BACKGROUND: At present, the need for vitamin C supplementation for pregnant smokers has not been fully studied. This study is aimed at investigating whether vitamin C supplementation for pregnant smoking women can improve the pulmonary function of their offspring. METHODS: Four databases were searched from inception to April 1, 2023 for studies on the effect of vitamin C supplementation to pregnant smokers on the pulmonary function of their offspring. Meanwhile, the reference lists of relevant studies were manually searched. The risk of bias in the included studies was assessed using the Cochrane Collaboration tool, and the data was analyzed using STATA/SE 17.0. RESULTS: Four randomized controlled trials (RCTs), all of high quality, were enrolled in this meta-analysis, including 787 pregnant women. The offspring of pregnant smokers who received vitamin C supplementation exhibited improved Forced Expiratory Flow between 25 and 75% (FEF25-75), FEF50, FEF75, and Forced Vital Capacity (FVC) compared to those who did not receive vitamin C supplementation. However, there was no statistically significant difference in Forced Expiratory Volume at 0.5 s (FEV0.5) and the ratio of FEV0.5 to FVC between the offspring of pregnant smokers who received vitamin C and the control group. CONCLUSION: Vitamin C supplementation for smoking pregnant women may enhance the pulmonary function of their offspring, particularly in FEF25-75, FEF50, FEF75, and FVC. Nevertheless, there are no significant differences in FEV0.5 and the FEV0.5/FVC ratio. These findings suggest that vitamin C supplementation has potential benefits for specific pulmonary function. Further studies are needed to comprehensively assess the effects of vitamin C on pulmonary function in the context of maternal smoking during pregnancy.

Assessment of the quality, diagnosis, and therapeutic recommendations of clinical practice guidelines on patients with Helicobacter pylori infection: A systematic review.

We conducted this study to systematically review and assess the current clinical practice guidelines (CPGs) related to the diagnosis and treatment of Helicobacter pylori (H. pylori) infection. The aim was to evaluate the quality of these included CPGs and provide clinicians with a convenient and comprehensive reference for updating their own CPGs. We searched four databases to identify eligible CPGs focusing on H. pylori diagnosis and treatment recommendations. The results were presented using evidence mappings. Quality and clinical applicability were assessed comprehensively using AGREE-II and AGREE-REX. Statistical tests, specifically Bonferroni tests, were employed to compare the quality between evidence-based guidelines and consensus. A total of 30 eligible CPGs were included, comprising 17 consensuses and 13 guidelines. The quality showed no statistical significance between consensuses and guidelines, mainly within the moderate to low range. Notably, recommendations across CPGs exhibited inconsistency. Nevertheless, concerning diagnosis, the urea breath test emerged as the most frequently recommended method for testing H. pylori. Regarding treatment, bismuth quadruple therapy stood out as the predominantly recommended eradication strategy, with high-dose dual therapy being a newly recommended option. Our findings suggest the need for specific organizations to update their CPGs on H. pylori or refer to recently published CPGs. Specifically, CPGs for pediatric cases require improvement and updating, while a notable absence of CPGs for the elderly was observed. Furthermore, there is a pressing need to improve the overall quality of CPGs related to H. pylori. Regarding recommendations, additional evidence is essential to elucidate the relationship between H. pylori infection and other diseases and refine test indications. Clinicians are encouraged to consider bismuth quadruple or high-dose dual therapy, incorporating locally sensitive antibiotics, as empirical radical therapy. .

Association Between Anti-Müllerian Hormone and Early Spontaneous Abortion in Assisted Reproduction Treatment: A Case-Control Study Integrated with Biological Evidence.

Early spontaneous abortion (ESA) is a common adverse pregnancy outcome mainly attributed to embryo chromosomal abnormalities. However, as a quantitative marker, whether the anti-Müllerian hormone (AMH) can reflect oocyte quality is still controversial. By integrating biological evidence and adjusting many cofounders, this study aimed to clarify the controversies about the association between AMH and ESA caused by embryo aneuploidy during assisted reproductive technology (ART) treatment. We strictly preselected 988 patients receiving first ART treatment for analyzing clinical data, while 55 of them acquired chorionic villi karyotype results. In addition, 373 biopsied embryos from 126 patients receiving preimplantation genetic diagnosis (PGT) were tracked to compare embryo karyotypes. Univariate and multiple factor regressions were applied to analyze the risk factors leading to ESA. As covariates unadjusted, AMH (odds ratio 0.87, 95% CI 0.82-0.93) was the significant variable contributing to ESA. However, AMH played no significant role in the following regression models after age was adjusted. Also, AMH had no significant association with ESA in most age-adjusted subgroups, except in the male factors engaged subgroup. Additionally, compared to the patients with euploid chorionic villi karyotypes, those with aneuploid karyotypes were older and acquired fewer oocytes, yet their AMH levels were not significantly different. Furthermore, the embryo aneuploidy was independent of AMH while associated with maternal age, retrieved oocyte number, and embryo quality. This study suggested that AMH was unassociated with the ESA caused by embryo aneuploidy in ART therapy. As a critical cofounder, age remains the variable closely related to ESA.

Supplemental low-dose esketamine to propofol versus propofol alone on perioperative characteristics in children undergoing surgery: a prospective randomized controlled trial.

BACKGROUND: Limited data exist regarding the use of the esketamine-propofol combination (esketofol) in pediatric surgery. This study aimed to investigate the effect of esketofol versus propofol alone on the perioperative characteristics of children undergoing minor surgery. METHODS: Eighty-four children aged two to six years were randomly assigned to either the propofol group or the esketofol group. Intraoperative outcomes included bispectral index, dosage of anesthetics, and extubation time. Postoperative outcomes comprised oropharyngeal airway usage, time to orientation, time to eye-opening, length of stay in the post-anesthesia care unit, the need for rescue opioids, pain rating using the Face, Legs, Activity, Cry, Consolability (FLACC) Scale, Pediatric Anesthesia Emergence Delirium Score, nausea and vomiting, and psychotomimetic symptoms. The FLACC pain score was the primary outcome, and the remaining parameters were considered secondary outcomes. RESULTS: The FLACC Score (2 [1, 3.3] vs. 4 [3, 5.3], P<0.001) and frequency of rescue opioids (14.3% vs. 33.3%, P=0.040) were significantly lower, while Bispectral Index (BIS) was higher (P<0.001) in the esketofol group compared with the propofol group. Moreover, the time to orientation and length of stay in the post-anesthesia care unit (PACU) were significantly longer in the esketofol group compared with the propofol group (P=0.029 and P=0.025, respectively). The other outcomes were similar between the two groups. CONCLUSIONS: Esketofol reduces postoperative pain and the need for rescue opioids, but it extends recovery time in the PACU and increases BIS without affecting other outcomes.

Value of Image Biomarkers Based on Dual-Energy Computed Tomography Angiography Material Separation Technique in Predicting Early Hematoma Expansion in Spontaneous Intracerebral Hemorrhage.

OBJECTIVE: This study aims to investigate the connection between the leakage sign (LS) and hematoma expansion (HE) in cases of spontaneous intracerebral hemorrhage. The investigation employs dual-energy computed tomography angiography (DECTA). METHODS: A prospective cohort study was conducted, in which clinical and DECTA imaging data were collected from intracerebral hemorrhage patients within 6 hours of onset between January 2021 and June 2023. Exposure factors included DE-LS and traditional imaging biomarkers. The occurrence of HE on computed tomography rescanned within 24 hours was the observed outcome. Exposed and confounding factors were considered in both univariate and multivariate regression analyses based on the results. Logistic and adjusted Poisson regressions were employed, and odds ratios (ORs) and relative risks (RRs) were calculated with 95% confidence intervals. RESULTS: The study enrolled a total of 90 patients, of whom 32 cases manifested HE, while 58 cases did not exhibit HE. Univariate analysis revealed statistically significant differences in parameters such as admission diastolic blood pressure, C-reactive protein, Glasgow Coma Scale, baseline hematoma volume, and imaging biomarkers like DE-spot sign and DE-LS. The OR value of DE-LS was determined as 48.21, with an RR value of 7.51. Multivariate adjusted Poisson regression analysis demonstrated that DE-LS was a robust independent predictor (RR = 4.11, 95% confidence interval: 1.49-11.35; P < 0.001). CONCLUSIONS: DECTA-based DE-LS stands out as an independent predictor of HE. The utilization of RR values over OR values is endorsed when assessing the risk of HE prediction.

D-Mannose promotes recovery from experimental colitis by inducing AMPK phosphorylation to stimulate epithelial repair.

Delayed mucosal healing and impaired intestinal epithelial barrier function have been implicated in the pathogenesis of ulcerative colitis (UC). Accordingly, restoration of epithelial barrier function as a means to reshape mucosal homeostasis represents an important strategy for use in the treatment of UC. In this study, we examined the role and mechanisms of D-mannose in the recovery of colitis as assessed in both animal and cell models. We found that D-mannose ameliorated inflammation, promoted mucosal healing in the colon and therefore was able to induce the recovery of UC. Furthermore, D-mannose increased the expression of tight junction (TJ) proteins and reduced the intestinal permeability during the recovery of colitis. Moreover, D-mannose inhibited M1 macrophage polarization and promoted M2 macrophage polarization via inducing AMPK phosphorylation while reducing mTOR phosphorylation in both models. In addition, increased TJ protein expression and decreased paracellular permeability were observed in NCM460 cells when incubated with the supernatants of D-mannose-treated RAW264.7 cells, suggesting that M1/M2 polarization induced by D-mannose modulates the expression of TJ proteins. Further study showed that D-mannose significantly upregulated the expression of TJ proteins in DSS-treated NCM460 cells by inducing AMPK phosphorylation, indicating a direct protective effect on epithelial cells. Finally, the protective effects of D-mannose were significantly abrogated by the presence of compound C, an AMPK inhibitor. Taken together, our data indicate that D-mannose can alleviate inflammation and foster epithelial restitution in UC recovery by inducing the TJ protein expression, which are achieved by inducing AMPK phosphorylation in the epithelium and/or macrophages.

Molecular basis for cellular retinoic acid-binding protein 1 in modulating CaMKII activation.

Introduction: Cellular retinoic acid (RA)-binding protein 1 (CRABP1) is a highly conserved protein comprised of an anti-parallel, beta-barrel, and a helix-turn-helix segment outside this barrel. Functionally, CRABP1 is thought to bind and sequester cytosolic RA. Recently, CRABP1 has been established as a major mediator of rapid, non-genomic activity of RA in the cytosol, referred to as "non-canonical" activity. Previously, we have reported that CRABP1 interacts with and dampens the activation of calcium-calmodulin (Ca2+-CaM)-dependent kinase 2 (CaMKII), a major effector of Ca2+ signaling. Through biophysical, molecular, and cellular assays, we, herein, elucidate the molecular and structural mechanisms underlying the action of CRABP1 in dampening CaMKII activation. Results: We identify an interaction surface on CRABP1 for CaMKII binding, located on the beta-sheet surface of the barrel, and an allosteric region within the helix segment outside the barrel, where both are important for interacting with CaMKII. Molecular studies reveal that CRABP1 preferentially associates with the inactive form of CaMKII, thereby dampening CaMKII activation. Alanine mutagenesis of residues implicated in the CaMKII interaction results in either a loss of this preference or a shift of CRABP1 from associating with the inactive CaMKII to associating with the active CaMKII, which corresponds to changes in CRABP1's effect in modulating CaMKII activation. Conclusions: This is the first study to elucidate the molecular and structural basis for CRABP1's function in modulating CaMKII activation. These results further shed insights into CRABP1's functional involvement in multiple signaling pathways, as well as its extremely high sequence conservation across species and over evolution.

A novel 3D bilayer hydrogel tri-culture system for studying functional motor units.

BACKGROUND: A motor unit (MU) is formed by a single alpha motor neuron (MN) and the muscle fibers it innervates. The MU is essential for all voluntary movements. Functional deficits in the MU result in neuromuscular disorders (NMDs). The pathological mechanisms underlying most NMDs remain poorly understood, in part due to the lack of in vitro models that can comprehensively recapitulate multistage intercellular interactions and physiological function of the MU. RESULTS: We have designed a novel three-dimensional (3D) bilayer hydrogel tri-culture system where architecturally organized MUs can form in vitro. A sequential co-culture procedure using the three cell types of a MU, MN, myoblast, and Schwann cell was designed to construct a co-differentiating tri-culture on a bilayer hydrogel matrix. We utilized a µ-molded hydrogel with an additional Matrigel layer to form the bilayer hydrogel device. The µ-molded hydrogel layer provides the topological cues for myoblast differentiation. The Matrigel layer, with embedded Schwann cells, not only separates the MNs from myoblasts but also provides a proper micro-environment for MU development. The completed model shows key MU features including an organized MU structure, myelinated nerves, aligned myotubes innervated on clustered neuromuscular junctions (NMJs), MN-driven myotube contractions, and increases in cytosolic Ca2+ upon stimulation. CONCLUSIONS: This organized and functional in vitro MU model provides an opportunity to study pathological events involved in NMDs and peripheral neuropathies, and can serve as a platform for physiological and pharmacological studies such as modeling and drug screening. Technically, the rational of this 3D bilayer hydrogel co-culture system exploits multiple distinct properties of hydrogels, facilitating effective and efficient co-culturing of diverse cell types for tissue engineering.

Quality evaluation index development for nutritional management in patients with nasopharyngeal carcinoma during peri-radiotherapy.

OBJECTIVES: It is necessary to construct an evaluation index for patients with nasopharyngeal carcinoma during peri-radiotherapy to provide a reference for the evaluation of the quality of nutritional management of patients with nasopharyngeal carcinoma during peri-radiotherapy. The aim of this study was to construct a set of scientific, comprehensive, and feasible indicators for evaluating the quality of nutrition management in patients with nasopharyngeal carcinoma during peri-radiotherapy to provide a unified reference basis for objective nutritional evaluation of these patients during the peri-radiotherapy period and to provide insights to the clinical treatment and care of these patients. METHODS: A multidisciplinary research team was set up from December 2021 to April 2022. We took the three-dimensional quality structure model as the theoretical framework; based on the literature review, the first draft of the nutrition management quality evaluation index for patients with nasopharyngeal carcinoma during peri-radiotherapy was formed by a semi-structured interview. The Delphi correspondence method was used to survey 18 experts from 12 cities in China. The multidimensional analytical hierarchy process was used to determine the evaluation index and weight of nutrition management quality of patients with nasopharyngeal carcinoma during peri-radiotherapy. RESULTS: The effective questionnaire recovery rates of the two rounds of letters were 90.005% and 100%, respectively, and the expert authority coefficients were 0.906 and 0.918, respectively. The Kendall harmony coefficients of the two rounds of letters were 0.271 to 0.313 and 0.309 to 0.349, respectively. The nutrition management quality evaluation index of patients with nasopharyngeal carcinoma during peri-radiotherapy was constructed and included 3 first-level indexes, 10 second-level indexes, and 71 third-level indexes. CONCLUSION: The evaluation index of the nutrition management quality of patients with nasopharyngeal carcinoma during peri-radiotherapy is scientific and reliable, and it may have a certain guiding significance for nurses to evaluate the quality of nutrition management of these patients during this period.

Giant breast phyllodes tumor with silent thromboembolism: A case report.

BACKGROUND: Phyllodes tumor (PT) is a solid fibroepithelial breast lesion with proliferation of stromal and epithelial elements, usually presents with a rapidly expanding feature. Venous thromboembolism (VTE) have been reported to increase the burden in terms of mortality and morbidity of malignant tumor, and associate with worsened survival. However, benign PTs with silent thromboembolism that have not yet been reported, we report an unusual case of massive benign PT that grew on the left side of the breast in a cauliflower-shaped form and presented severe chronic blood loss and deep VTE. CASE: A 37-year-old woman with uncontrolled pain presented a rapidly enlarging left breast mass, measuring approximately 30 × 20 × 15 cm3 that first started 25 years ago. color Doppler ultrasound showed a large mass lesion on the left breast and deep VTE, several enlarged lymph nodes in the left axilla and mediastinum, which presented a malignant character. However, the biopsies of the mass did not show evidence of malignancy and the pathology result was considered to be benign PT. The patient was treated with an inferior vena cava and anticoagulation, the operation was arranged according to the surgical procedure, the patient recovered very well after mastectomy. CONCLUSION: This case is unique in that the giant breast mass presented with malignant character, was eventually pathologically confirmed to be benign PT, and it's rare that the benign tumor accompanied with silent thromboembolism. This finding describes the atypia features of giant benign PT and reminds the surgeon to consider the factor of VTE and risk when encountering ulcerative benign breast tumor and avoid excessive treatment.

The study of the effectiveness of design-based engineering learning: the mediating role of cognitive engagement and the moderating role of modes of engagement.

Aim: Design-based engineering learning (DBEL) offers a potentially valuable approach to engineering education, but its mechanism of action has yet to be verified by empirical studies. Accordingly, the present study aimed to establish whether DBEL produces better learning outcomes, thereby building a strong, empirically grounded case for further research into engineering education. Methods: To build a more comprehensive model of design-based engineering learning, the variables of cognitive engagement (the mediator) and modes of engagement (the moderator) were introduced to build a theoretical process model. Questionnaires and multiple linear regression analysis were used to verify the model. Results and discussion: All four features of DBEL (design practice, interactive reflection, knowledge integration, and circular iteration) were found to exert significant and positive effects on learning outcomes. Moreover, cognitive engagement was found to both fully and partially mediate the relationships between these features and the outcomes of engineering learning; under two different modes of engagement, the positive effects of the learning features on cognitive engagement differed significantly. Conclusion: The paper concluded the following: (1) a design-based learning approach can enhance engineering students' learning outcomes, (2) cognitive engagement mediates between design-based engineering learning and learning outcomes (3) a systematic mode of engagement produces better learning outcomes than a staged modes of engagement.

Novel insights into tumorigenesis and prognosis of endometrial cancer through systematic investigation and validation on mitophagy-related signature.

In-depth studies on the pathogenesis of endometrial cancer (EC) are critical because of the increasing global incidence of EC. Mitophagy, a mitochondrial quality control process, plays an important role in carcinogenesis and tumor progression. This study aimed to develop a novel mitophagy-based signature to predict the tumorigenesis and prognosis of EC. Data was downloaded from The Cancer Genome Atlas and Gene Expression Omnibus databases, and 29 mitophagy-related genes were downloaded from the Pathway Unification Database. EC patients were classified into two risk groups based on the two-key- gene signature, TOMM40 and MFN1, which were constructed using Cox regression analysis. A better prognosis was noted in the low-risk group. The model was validated for four aspects: clinical features, mutation status, clinical therapeutic response, and immune cell infiltration status. Moreover, according to the contribution to the risk model, TOMM40 was selected for further in vitro experiments. The silencing of TOMM40 inhibited mitochondrial degradation; suppressed cell proliferation; induced cell apoptosis and G1 phase cell cycle arrest; inhibited migration, invasion, and epithelial-mesenchymal transition; and suppressed cell stemness. In conclusion, the mitophagy-related risk score provides a novel perspective for survival and drug selection during the individual treatment of EC patients. TOMM40 serves as an oncogene in EC and promotes tumor progression via a mitophagy-related pathway. Thus, TOMM40 is a potential therapeutic target in EC.

Shortwave infrared diffuse optical wearable probe for quantification of water and lipid content in emulsion phantoms using deep learning.

Significance: The shortwave infrared (SWIR, ∼900 to 2000 nm) holds promise for label-free measurements of water and lipid content in thick tissue, owed to the chromophore-specific absorption features and low scattering in this range. In vivo water and lipid estimations have potential applications including the monitoring of hydration, volume status, edema, body composition, weight loss, and cancer. To the best of our knowledge, there are currently no point-of-care or wearable devices available that exploit the SWIR wavelength range, limiting clinical and at-home translation of this technology. Aim: To design and fabricate a diffuse optical wearable SWIR probe for water and lipid quantification in tissue. Approach: Simulations were first performed to confirm the theoretical advantage of SWIR wavelengths over near infrared (NIR). The probe was then fabricated, consisting of light emitting diodes at three wavelengths (980, 1200, 1300 nm) and four source-detector (S-D) separations (7, 10, 13, 16 mm). In vitro validation was then performed on emulsion phantoms containing varying concentrations of water, lipid, and deuterium oxide (D2O). A deep neural network was developed as the inverse model for quantity estimation. Results: Simulations indicated that SWIR wavelengths could reduce theoretical water and lipid extraction errors from ∼6% to ∼1% when compared to NIR wavelengths. The SWIR probe had good signal-to-noise ratio (>32 dB up to 10 mm S-D) and low drift (<1.1% up to 10 mm S-D). Quantification error in emulsion phantoms was 2.1±1.1% for water and -1.2±1.5% for lipid. Water estimation during a D2O dilution experiment had an error of 3.1±3.7%. Conclusions: This diffuse optical SWIR probe was able to quantify water and lipid contents in vitro with good accuracy, opening the door to human investigations.