Time-Series MR Images Identifying Complete Response to Neoadjuvant Chemotherapy in Breast Cancer Using a Deep Learning Approach.

BACKGROUND: Pathological complete response (pCR) is an essential criterion for adjusting follow-up treatment plans for patients with breast cancer (BC). The value of the visual geometry group and long short-term memory (VGG-LSTM) network using time-series dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) for pCR identification in BC is unclear. PURPOSE: To identify pCR to neoadjuvant chemotherapy (NAC) using deep learning (DL) models based on the VGG-LSTM network. STUDY TYPE: Retrospective. POPULATION: Center A: 235 patients (47.7 ± 10.0 years) were divided 7:3 into training (n = 164) and validation set (n = 71). Center B: 150 patients (48.5 ± 10.4 years) were used as test set. FIELD STRENGTH/SEQUENCE: 3-T, T2-weighted spin-echo sequence imaging, and gradient echo DCE sequence imaging. ASSESSMENT: Patients underwent MRI examinations at three sequential time points: pretreatment, after three cycles of treatment, and prior to surgery, with tumor regions of interest manually delineated. Histopathology was the gold standard. We used VGG-LSTM network to establish seven DL models using time-series DCE-MR images: pre-NAC images (t0 model), early NAC images (t1 model), post-NAC images (t2 model), pre-NAC and early NAC images (t0 + t1 model), pre-NAC and post-NAC images (t0 + t2 model), pre-NAC, early NAC and post-NAC images (t0 + t1 + t2 model), and the optimal model combined with the clinical features and imaging features (combined model). The models were trained and optimized on the training and validation set, and tested on the test set. STATISTICAL TESTS: The DeLong, Student's t-test, Mann-Whitney U, Chi-squared, Fisher's exact, Hosmer-Lemeshow tests, decision curve analysis, and receiver operating characteristics analysis were performed. P < 0.05 was considered significant. RESULTS: Compared with the other six models, the combined model achieved the best performance in the test set yielding an AUC of 0.927. DATA CONCLUSION: The combined model that used time-series DCE-MR images, clinical features and imaging features shows promise for identifying pCR in BC. TECHNICAL EFFICACY: Stage 4.

Endothelial knockdown of the tumor suppressor, WWOX, increases inflammation in ventilator-induced lung injury.

Chronic cigarette smoke exposure decreases lung expression of WWOX which is known to protect the endothelial barrier during infectious models of acute respiratory distress syndrome (ARDS). Proteomic analysis of WWOX-silenced endothelial cells (ECs) was done using tandem mass tag mass spectrometry (TMT-MS). WWOX-silenced ECs as well as those isolated from endothelial cell Wwox knockout (EC Wwox KO) mice were subjected to cyclic stretch (18% elongation, 0.5 Hz, 4 h). Cellular lysates and media supernatant were harvested for assays of cellular signaling, protein expression, and cytokine release. These were repeated with dual silencing of WWOX and zyxin. Control and EC Wwox KO mice were subjected to high tidal volume ventilation. Bronchoalveolar lavage fluid and mouse lung tissue were harvested for cellular signaling, cytokine secretion, and histological assays. TMT-MS revealed upregulation of zyxin expression during WWOX knockdown which predicted a heightened inflammatory response to mechanical stretch. WWOX-silenced ECs and ECs isolated from EC Wwox mice displayed significantly increased cyclic stretch-mediated secretion of various cytokines (IL-6, KC/IL-8, IL-1ß, and MCP-1) relative to controls. This was associated with increased ERK and JNK phosphorylation but decreased p38 mitogen-activated kinases (MAPK) phosphorylation. EC Wwox KO mice subjected to VILI sustained a greater degree of injury than corresponding controls. Silencing of zyxin during WWOX knockdown abrogated stretch-induced increases in IL-8 secretion but not in IL-6. Loss of WWOX function in ECs is associated with a heightened inflammatory response during mechanical stretch that is associated with increased MAPK phosphorylation and appears, in part, to be dependent on the upregulation of zyxin.NEW & NOTEWORTHY Prior tobacco smoke exposure is associated with an increased risk of acute respiratory distress syndrome (ARDS) during critical illness. Our laboratory is investigating one of the gene expression changes that occurs in the lung following smoke exposure: WWOX downregulation. Here we describe changes in protein expression associated with WWOX knockdown and its influence on ventilator-induced ARDS in a mouse model.

Synergy of Subgroup J Avian Leukosis Virus and Chicken Infectious Anemia Virus Enhances the Pathogenicity in Chickens.

Subgroup J avian leukemia virus (ALV-J) and chicken infectious anemia virus (CIAV) are widely acknowledged as significant immunosuppressive pathogens that commonly co-infect chickens, causing substantial economic losses in the poultry industry. However, whether co-infection of ALV-J and CIAV have synergistic pathogenicity remains uncertain. To explore their synergistic pathogenesis, we established a co-infection model of ALV-J and CIAV in HD11 cells and specific-pathogen-free (SPF) chickens. We discovered that ALV-J and CIAV can synergistically promote the secretion of IL-6, IL-10, IFN-α, and IFN-γ and apoptosis in HD11 cells. In vivo, compared to the ALV-J and CIAV mono-infected group, the mortality increased significantly by 27% (20 to 47%) and 14% (33 to 47%) in the co-infected group, respectively. We also discovered that ALV-J and CIAV synergistically inhibited weight gain and exhibited more severe organ damage in co-infected chickens. Furthermore, we found that CIAV can promote the replication of ALV-J in HD11 cells and significantly enhance ALV-J viral load in blood and tissues of co-infected chickens, but ALV-J cannot promote the replication of CIAV. Moreover, by measuring the immune organ indexes and proportions of blood CD3+CD4+ and CD3+CD8+ lymphocytes, more serious instances of immunosuppression were observed in ALV-J and CIAV co-infected chickens than in mono-infected chickens. Taken together, our findings demonstrate that ALV-J and CIAV synergistically enhance pathogenicity and immunosuppression.

Impact of coexisting type 2 diabetes mellitus on the urinary microbiota of kidney stone patients.

Objectives: Type 2 diabetes mellitus (T2DM) commonly complicates kidney stone disease (KSD). Our objective is to investigate the variations in the urinary microbiota between individuals with KSD alone and those with KSD plus T2DM. This exploration could have implications for disease diagnosis and treatment strategies. Methods: During lithotripsy, a ureterscope was employed, and 1 mL of urine was collected from the renal pelvis after bladder disinfection. Sequencing targeting the V3-V4 hypervariable region was performed using the 16S rRNA and Illumina Novaseq platform. Results: The Shannon index showed a significant decrease in the KSD plus T2DM group compared to the KSD-only group (false discovery rate = 0.041). Principal Coordinate Analysis (PCoA) demonstrated a distinct bacterial community in the KSD plus T2DM group compared to the KSD-only group (false discovery rate = 0.027). The abundance of Sphingomonas, Corynebacterium, and Lactobacillus was significantly higher in the KSD plus T2DM group than in the KSD-only group (false discovery rate < 0.05). Furthermore, Enhydrobacter, Chryseobacterium, and Allobaculum were positively correlated with fasting blood glucose and HbA1c values (P < 0.05). Conclusions: The urinary microbiota in the renal pelvis exhibits differences between patients with KSD plus T2DM and those with KSD alone. Further studies employing animal models are necessary to validate these distinctions, potentially paving the way for therapeutic developments based on the urinary microbiota.

A multifunctional CaCO3 bioreactor coated with coordination polymers enhances cancer immunotherapy.

Designing effective nanomedicines to induce durable anti-tumor immunity represents a promising strategy for improving moderate immune stimulation. In this study, we engineered a multifunctional nanoreactor (named SCGFP NPs) for remodeling the tumor microenvironment (TME) to improve the therapeutic efficacy of immunotherapy. The core of SCGFP NPs consists of CaCO3 loaded with SN38, prepared by the gas diffusion method, and coated with a significant amount of gallic acid-Fe3+-PEG coordination polymer on the surface. In the acidic TME, SCGFP NPs explosively release exogenous Ca2+ and SN38. The SN38-induced intracellular Ca2+ accumulation and exogenous Ca2+ synergistically trigger immunogenic cell death (ICD) through sustained Ca2+ overload. The ablation of tumors with high-intensity photothermal therapy (PTT) by near-infrared (NIR) irradiation of GA-Fe3+ induces tumor cell necrosis, further enhancing ICD activation. Additionally, SN38 upregulates PD-L1, amplifying tumor responsiveness to immune checkpoint inhibitors (ICIs). This study indicates that SCGFP NPs, through the integration of a trimodal therapeutic strategy, hold enormous potential for various types of tumor immunotherapy through distinct mechanisms or synergistic effects.

Breast masses with rim enhancement on contrast-enhanced mammography: morphological and enhancement features for diagnosis and differentiation of benign and malignant.

OBJECTIVES: To investigate the imaging characteristics and clinicopathological features of rim enhancement of breast masses demonstrated on contrast-enhanced mammography (CEM). METHODS: 67 cases of breast lesions confirmed by pathology and showing rim enhancement on CEM examinations were analyzed. The lesions were divided into benign and malignant groups, and the morphological and enhanced features were described. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated separately for each morphology descriptor to evaluate the diagnostic ability of each indicator. RESULTS: There were 35 (52.2%) malignant and 32 (47.8%) benign lesions. There are significant differences in the morphological and enhanced features between benign and malignant lesions. 29/35 (82.9%) malignant lesions exhibited irregular shapes, and 31/35 (88.6%) showed indistinct margins. 28/35 (80%) malignant lesions displayed strong enhancement on CEM, while 12/32 (37.5%) benign lesions exhibited weak enhancement (P = 0.001). Malignant lesions showed a higher incidence of unsmooth inner walls than benign lesions (28/35 vs 7/32; P <.001). Lesion margins showed high sensitivity of 88.57% and NPV of 81.8%. The presence of suspicious calcifications had the highest specificity of 100% and PPV of 100%. The diagnostic sensitivity, specificity, PPV, and NPV of the combined parameters were 97.14%, 93.15%, 94.44%, and 96.77%, respectively. CONCLUSIONS: The assessment of morphological and enhanced features of breast lesions exhibiting rim enhancement on CEM can improve the differentiation between benign and malignant breast lesions. ADVANCES IN KNOWLEDGE: This article provides a reference for the differential diagnosis of ring enhanced lesions on CEM.

Association of reduced cerebrospinal fluid NPTX2 levels with postoperative delirium in patients undergoing knee/hip replacement: a prospective cohort study.

BACKGROUND: Postoperative delirium (POD) is a common complication with poor prognosis in the elderly, but its mechanism has not been fully elucidated. There is evidence that the changes in synaptic activity in the brain are closely related to the occurrence of POD. And neuronal pentraxin 2 (NPTX2) can regulate synaptic activity in vivo. AIMS: This study aims to explore whether decreased NPTX2 levels affects POD and whether the cerebrospinal fluid (CSF) biomarkers of POD mediate this association. METHODS: In this prospective cohort study, we interviewed patients with knee/hip replacement 1 day before surgery to collect patient information and assess their cognitive function. CSF was extracted for measuring the CSF levels of NPTX2 and other POD biomarkers on the day of surgery. And postoperative follow-up visits were performed 1-7 days after surgery. RESULTS: Finally, 560 patients were included in the study. The patients were divided into POD group and NPOD (non-POD) group. The POD group had a median age of 80 years, a female proportion of 45%, a median BMI of 24.1 kg/m2, and a median years of education of 9 years. The Mann-Whitney U test showed that CSF NPTX2 levels were significantly lower in POD group, compared with the NPOD group (P < 0.05). Univariate binary logistic regression analysis showed that reduced CSF levels of NPTX2 protected against POD (crude OR = 0.994, 95% CI 0.993-0.995, P < 0.001). The receiver-operating characteristic (ROC) curve indicated that CSF NPTX2 level had high predictive value for POD. Mediation analyses showed that CSF T-tau (mediating proportion = 21%) and P-tau (mediating proportion = 29%) had significant mediating effects on the association between CSF NPTX2 and POD. CONCLUSION: CSF NPTX2 levels were associated with the occurrence of POD. Low CSF NPTX2 levels may be an independent protective factor for POD. CSF T-tau and P-tau could mediate the association between CSF NPTX2 and POD occurrence. CLINICAL TRIAL REGISTRATION: The trial registration number (TRN): ChiCTR2200064740, Date of Registration: 2022-10-15.

Using time-series chest radiographs and laboratory data by machine learning for identifying pulmonary infection and colonization of Acinetobacter baumannii.

BACKGROUND: Accurately distinguishing between pulmonary infection and colonization in patients with Acinetobacter baumannii is of utmost importance to optimize treatment and prevent antibiotic abuse or inadequate therapy. An efficient automated sorting tool could prompt individualized interventions and enhance overall patient outcomes. This study aims to develop a robust machine learning classification model using a combination of time-series chest radiographs and laboratory data to accurately classify pulmonary status caused by Acinetobacter baumannii. METHODS: We proposed nested logistic regression models based on different time-series data to automatically classify the pulmonary status of patients with Acinetobacter baumannii. Advanced features were extracted from the time-series data of hospitalized patients, encompassing dynamic pneumonia indicators observed on chest radiographs and laboratory indicator values recorded at three specific time points. RESULTS: Data of 152 patients with Acinetobacter baumannii cultured from sputum or alveolar lavage fluid were retrospectively analyzed. Our model with multiple time-series data demonstrated a higher performance of AUC (0.850, with a 95% confidence interval of [0.638-0.873]), an accuracy of 0.761, a sensitivity of 0.833. The model, which only incorporated a single time point feature, achieved an AUC of 0.741. The influential model variables included difference in the chest radiograph pneumonia score. CONCLUSION: Dynamic assessment of time-series chest radiographs and laboratory data using machine learning allowed for accurate classification of colonization and infection with Acinetobacter baumannii. This demonstrates the potential to help clinicians provide individualized treatment through early detection.

Zeaamine, a new amine from roots of Zea mays and its cytotoxic activity against CT26 and SW480 cell lines.

A new amine, zeaamine (1), along with nine known compounds (2-10), were isolated from the roots of Zea mays. Among these, compound 2 was first isolated from this plant, and compound 3 was first isolated from the roots. In the current investigation, the cytotoxicity against CT26 and SW480 cells of the compounds were evaluated. Zeaamine (1) exhibited moderately affected CT26 and SW480 cells with IC50 values of 17.91 and 10.21 µM.

Safety analysis of immediate breast reconstruction with a deep inferior epigastric perforator (DIEP) flap in the post-COVID-19 era: a comparison between pre- and post-pandemic cohorts.

Background: The demand for immediate breast reconstruction with a deep inferior epigastric perforator (DIEP) flap is recovering as coronavirus disease 2019 (COVID-19) transitions from a pandemic to an endemic. This study sought to evaluate the safety of resuming DIEP flap reconstruction in the post-COVID-19 era. Methods: Consecutive breast cancer patients who underwent immediate breast reconstruction with a DIEP flap at the Comprehensive Breast Health Center, Ruijin Hospital were retrospectively included in the study. The patients were divided into a post-pandemic group (Group A) and a pre-pandemic group (Group B). The clinicopathological factors, surgical procedures, and rates of post-operative complications were compared between the two groups using the Mann-Whitney U test and Chi-squared test. Results: A total of 167 patients were included in the study, of whom 119 (71.3%) were in Group A and 48 (28.7%) were in Group B. The two groups had similar clinicopathological features, including age (P=0.988), body mass index (P=0.504), and tumor, node, metastasis (TNM) stage (P=0.932). The Group A patients were more likely to receive single perforator DIEP flap transplantation than the Group B patients (n=28, 22.8% vs. n=3, 5.8%, P=0.007). There was a numerical decrease in the mean operating time of Group A patients compared to Group B patients (9.82 vs. 10.12 hours, P=0.172). The mean length of stay after the surgery was significantly shorter after the pandemic than before the pandemic (11.2 vs. 14.3 days, P<0.001). The complication rates between the two groups were similar. Conclusions: This study provides evidence that resuming DIEP reconstruction is safe in the post-COVID-19 era.

Atypical architectural distortion detection in digital breast tomosynthesis: a multi-view computer-aided detection model with ipsilateral learning.

Objective.Breast architectural distortion (AD), a common imaging symptom of breast cancer, is associated with a particularly high rate of missed clinical detection. In clinical practice, atypical ADs that lack an obvious radiating appearance constitute most cases, and detection models based on single-view images often exhibit poor performance in detecting such ADs. Existing multi-view deep learning methods have overlooked the correspondence between anatomical structures across different views.Approach.To develop a computer-aided detection (CADe) model for AD detection that effectively utilizes the craniocaudal (CC) and mediolateral oblique (MLO) views of digital breast tomosynthesis (DBT) images, we proposed an anatomic-structure-based multi-view information fusion approach by leveraging the related anatomical structure information between these ipsilateral views. To obtain a representation that can effectively capture the similarity between ADs in images from ipsilateral views, our approach utilizes a Siamese network architecture to extract and compare information from both views. Additionally, we employed a triplet module that utilizes the anatomical structural relationship between the ipsilateral views as supervision information.Main results.Our method achieved a mean true positive fraction (MTPF) of 0.05-2.0, false positives (FPs) per volume of 64.40%, and a number of FPs at 80% sensitivity (FPs@0.8) of 3.5754; this indicates a 6% improvement in MPTF and 16% reduction in FPs@0.8 compared to the state-of-the-art baseline model.Significance.From our experimental results, it can be observed that the anatomic-structure-based fusion of ipsilateral view information contributes significantly to the improvement of CADe model performance for atypical AD detection based on DBT. The proposed approach has the potential to lead to earlier diagnosis and better patient outcomes.

Targeting cancer-associated adipocyte-derived CXCL8 inhibits triple-negative breast cancer progression and enhances the efficacy of anti-PD-1 immunotherapy.

Cancer-associated adipocytes (CAAs), one of the primary stromal components, exhibit intimate crosstalk and release multiple cell factors mediating local and systemic biological effects. However, the role of CAAs in the regulation of systemic immune responses and their potential value in the clinical treatment of triple-negative breast cancer (TNBC) are not well described. Transcriptome sequencing was performed on CAA and normal adipocyte (NA) tissues isolated from surgically resected samples from TNBC patients and healthy controls. Cytokines, including C-X-C motif chemokine ligand 8 (CXCL8, also known as IL-8), secreted from NAs and CAAs were compared by transcriptome sequencing and enzyme-linked immunosorbent assay (ELISA). Proliferation, migration and invasion assays were employed to analyze the role of CAAs and CAA-derived CXCL8 (macrophage inflammatory protein-2 (MIP2) as a functional surrogate in mice). TNBC syngraft models were established to evaluate the curative effect of targeting CXCL8 in combination with anti-PD-1 therapies. Real-time quantitative polymerase chain reaction (RT-qPCR), western blotting (WB), polymerase chain reaction (PCR) array, flow cytometry, immunohistochemistry (IHC), and immunofluorescence (IF) were applied to analyze immune cell infiltration and epithelial-mesenchymal transition (EMT) markers. Specifically, we demonstrated that CAAs and CAA-derived CXCL8 played important roles in tumor growth, EMT, metastasis and tumor immunity suppression. CAA-derived CXCL8 remodeled the tumor immune microenvironment not only by suppressing CD4+ T and CD8+ T immune cell infiltration but also by upregulating CD274 expression in TNBC. The combination of targeting the CXCL8 pathway and blocking the PD-1 pathway synergistically increased the tumor immune response and inhibited tumor progression. Thus, our results highlight the molecular mechanisms and translational significance of CAAs in tumor progression and immune ecosystem regulatory effects and provide a better understanding of the potential clinical benefit of targeting CAA-derived CXCL8 in antitumor immunity and as a new therapeutic moiety in TNBC.

Effect of the index of cardiac electrophysiological balance on major adverse cardiovascular events in patients with diabetes complicated with coronary heart disease.

Purpose: To investigate the prognostic value of the index of cardio-electrophysiological balance (ICEB) and its association with major adverse cardiac events (MACE) and cardiovascular death in diabetic patients complicated with coronary heart disease. Methods: A total of 920 diabetic patients were enrolled in this longitudinal study. Participants were categorized into three groups based on their ICEB levels: normal ICEB, low ICEB, and high ICEB. The primary outcome was the occurrence of MACE, and secondary outcomes included cardiovascular death, coronary heart disease (CHD), heart failure (HF), and sudden cardiac arrest (SCA). Patients were followed for a median period of 3.26 years, and the associations between ICEB levels and various outcomes were evaluated. Results: Over the follow-up period, 46 (5.0%) MACE were observed in the normal ICEB group, 57 (6.2%) in the low ICEB group, and 62 (6.8%) in the high ICEB group. Elevated ICEB levels were found to be associated with a higher risk of MACE and cardiovascular death. A significant relationship between ICEB levels and the risk of MACE was observed for both genders. The risk of MACE increased with each unit increment in the ICEB index. However, the two-stage linear regression model did not outperform the single-line linear regression models in determining the threshold effect. Conclusion: This study demonstrates the potential utility of ICEB, derived from a standard non-invasive ECG, as a prognostic tool for predicting MACE and cardiovascular death in diabetic patients complicated with CVD. The associations between ICEB levels and the risk of MACE highlight the importance of understanding cardiac electrophysiological imbalances and their implications in CVD.

UCHL1 Regulates Radiation Lung Injury via Sphingosine Kinase-1.

GADD45a is a gene we previously reported as a mediator of responses to acute lung injury. GADD45a-/- mice express decreased Akt and increased Akt ubiquitination due to the reduced expression of UCHL1 (ubiquitin c-terminal hydrolase L1), a deubiquitinating enzyme, while GADD45a-/- mice have increased their susceptibility to radiation-induced lung injury (RILI). Separately, we have reported a role for sphingolipids in RILI, evidenced by the increased RILI susceptibility of SphK1-/- (sphingosine kinase 1) mice. A mechanistic link between UCHL1 and sphingolipid signaling in RILI is suggested by the known polyubiquitination of SphK1. Thus, we hypothesized that the regulation of SphK1 ubiquitination by UCHL1 mediates RILI. Initially, human lung endothelial cells (EC) subjected to radiation demonstrated a significant upregulation of UCHL1 and SphK1. The ubiquitination of EC SphK1 after radiation was confirmed via the immunoprecipitation of SphK1 and Western blotting for ubiquitin. Further, EC transfected with siRNA specifically for UCHL1 or pretreated with LDN-5744, as a UCHL1 inhibitor, prior to radiation were noted to have decreased ubiquitinated SphK1 in both conditions. Further, the inhibition of UCHL1 attenuated sphingolipid-mediated EC barrier enhancement was measured by transendothelial electrical resistance. Finally, LDN pretreatment significantly augmented murine RILI severity. Our data support the fact that the regulation of SphK1 expression after radiation is mediated by UCHL1. The modulation of UCHL1 affecting sphingolipid signaling may represent a novel RILI therapeutic strategy.

Exploring the role of miRNAs in early chicken embryonic development and their significance.

In the early stages of embryonic development, a precise and strictly controlled hierarchy of gene expression is essential to ensure proper development of all cell types and organs. To better understand this gene control process, we constructed a small RNA library from 1- to 5-day-old chick embryos, and identified 2,459 miRNAs including 827 existing, 695 known, and 937 novel miRNAs with bioinformatic analysis. There was absolute high expression of a number of miRNAs in each stage, including gga-miR-363-3p (Em1d), gga-miR-26a-5p (Em2d and Em3d), gga-miR-10a-5p (Em4d), and gga-miR-199-5p (Em5d). We evaluated enriched miRNA profiles, identifying VEGF, Insulin, ErbB, MAPK, Hedgehog, TLR and Hippo signaling pathways as primary regulatory mechanisms enabling complex morphogenetic transformations within tight temporal constraints. Pathway analysis revealed miRNAs as pivotal nodes of interaction, coordinating cascades of gene expression critical for cell fate determination, proliferation, migration, and differentiation across germ layers and developing organ systems. Weighted Gene Co-Expression Network Analysis (WGCNA) generated hub miRNAs whose modular connections spanned regulatory networks, including: gga-miR-181a-3p (blue module), coordinating immunegenesis and myogenesis; gga-miR-126-3p (brown module), regulating vasculogenesis and angiogenesis; gga-miR-302c-5p (turquoise module), enabling pluripotency and self-renew; and gga-miR-429-3p (yellow module), modulating neurogenesis and osteogenesis. The findings of this study extend the knowledge of miRNA expression in early embryonic development of chickens, providing insights into the intricate gene control process that helps ensure proper development.

Targeting glutamine metabolic reprogramming of SLC7A5 enhances the efficacy of anti-PD-1 in triple-negative breast cancer.

Background: Triple-negative breast cancer (TNBC) is a heterogeneous disease that is characterized by metabolic disruption. Metabolic reprogramming and tumor cell immune escape play indispensable roles in the tumorigenesis that leads to TNBC. Methods: In this study, we constructed and validated two prognostic glutamine metabolic gene models, Clusters A and B, to better discriminate between groups of TNBC patients based on risk. Compared with the risk Cluster A patients, the Cluster B patients tended to exhibit better survival outcomes and higher immune cell infiltration. In addition, we established a scoring system, the glutamine metabolism score (GMS), to assess the pattern of glutamine metabolic modification. Results: We found that solute carrier family 7 member 5 (SLC7A5), an amino acid transporter, was the most important gene and plays a vital role in glutamine metabolism reprogramming in TNBC cells. Knocking down SLC7A5 significantly inhibited human and mouse TNBC cell proliferation, migration, and invasion. In addition, downregulation of SLC7A5 increased CD8+ T-cell infiltration. The combination of a SLC7A5 blockade mediated via JPH203 treatment and an anti-programmed cell death 1 (PD-1) antibody synergistically increased the immune cell infiltration rate and inhibited tumor progression. Conclusions: Hence, our results highlight the molecular mechanisms underlying SLC7A5 effects and lead to a better understanding of the potential benefit of targeting glutamine metabolism in combination with immunotherapy as a new therapy for TNBC.

Proteomic profiling of purified avian leukosis virus subgroup J particles.

While the presence of host cell proteins in virions and their role in viral life cycles have been demonstrated in various viruses, such characteristics have remained largely unknown in avian leukosis virus (ALV). To investigate whether this is the case in ALV, we purified high-integrity and high-purity virions from the avian leukosis virus subgroup J (ALV-J) and subjected them to proteome analysis using nano LC-MS/MS. This analysis identified 53 cellular proteins that are incorporated into mature ALV-J virions, and we verified the reliability of the packaged cellular proteins through subtilisin digestion and immunoblot analysis. Functional annotation revealed the potential functions of these proteins in the viral life cycle and tumorigenesis. Overall, our findings have important implications for understanding the interaction between ALV-J and its host, and provide new insights into the cellular requirements that define ALV-J infection.

Effect of Dapagliflozin on Clinical Outcome after Drug-Eluting Stent Implantation in Elderly T2DM Patients: A Real-World Study.

Objective: To investigate the effect of dapagliflozin therapy on the clinical outcome of drug-eluting stent (DES) implantation in elderly patients with type 2 diabetes mellitus (T2DM). Methods: We retrospectively studied the real-world data of patients with coronary heart disease who received DES implantation in our hospital from May 2019 to May 2021. Baseline general data and laboratory results of patients were collected. All patients were followed up for two years after PCI, and the follow-up endpoints included in-stent restenosis, major adverse cardiovascular events (MACE), revascularization, rehospitalization, and all-cause mortality. Results: Compared with those before treatment, body mass index, systolic blood pressure, diastolic blood pressure, TG, TC, LDL-C, FBG, and HbA1c were decreased in both groups after treatment, while HDL-C was increased after treatment (P < 0.05). There were significant differences in BMI, systolic blood pressure, diastolic blood pressure, FBG, and HbA1c between the two groups before and after treatment. At the end of follow-up, the incidence of in-stent restenosis and MACE in the dapagliflozin group was lower than that in the nondapagliflozin group. K-M curve analysis showed a significant difference in in-stent restenosis and MACE after DES implantation between the dapagliflozin group and the nondapagliflozin group (logrankχ2 = 5.093, 4.524; P = 0.024, 0.033). Conclusion: In accurate clinical data, dapagliflozin could significantly improve the postoperative BMI, blood pressure, and blood glucose outcome of patients with T2DM complicated with coronary heart disease and positively impact in-stent restenosis and MACE.

Effect of mindfulness-based mind-body therapies in patients with non-specific low back pain-A network meta-analysis of randomized controlled trials.

Background/objectives: Although mindfulness-based mind-body therapy (MBMBT) is an effective non-surgical treatment for patients with non-specific low back pain (NLBP), the best MBMBT mode of treatment for NLBP patients has not been identified. Therefore, a network meta-analysis (NMA) was conducted to compare the effects of different MBMBTs in the treatment of NLBP patients. Methods: PubMed, EMBASE, Cochrane Central Register of Controlled Trials, and Web of Science databases were searched for randomized controlled trials (RCTs) applying MBMBT for the treatment of NLBP patients, with all of the searches ranging from the time of database creation to January 2023. After 2 researchers independently screened the literature, extracted information, and evaluated the risks of biases in the included studies, the data were analyzed by using Stata 16.0 software. Results: A total of 46 RCTs were included, including 3,886 NLBP patients and 9 MBMBT (Yoga, Ayurvedic Massage, Pilates, Craniosacral Therapy, Meditation, Meditation + Yoga, Qigong, Tai Chi, and Dance). The results of the NMA showed that Craniosacral Therapy [surface under the cumulative ranking (SUCRA): 99.2 and 99.5%] ranked the highest in terms of improving pain and disability, followed by Other Manipulations (SUCRA: 80.6 and 90.8%) and Pilates (SUCRA: 54.5 and 71.2%). In terms of improving physical health, Craniosacral Therapy (SUCRA: 100%) ranked the highest, followed by Pilates (SUCRA: 72.3%) and Meditation (SUCRA: 55.9%). In terms of improving mental health, Craniosacral Therapy (SUCRA: 100%) ranked the highest, followed by Meditation (SUCRA: 70.7%) and Pilates (SUCRA: 63.2%). However, in terms of improving pain, physical health, and mental health, Usual Care (SUCRA: 7.0, 14.2, and 11.8%, respectively) ranked lowest. Moreover, in terms of improving disability, Dance (SUCRA: 11.3%) ranked lowest. Conclusion: This NMA shows that Craniosacral Therapy may be the most effective MBMBT in treating NLBP patients and deserves to be promoted for clinical use. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/, PROSPERO [CRD42023389369].

Primary prostate Burkitt's lymphoma resected with holmium laser enucleation of the prostate: A rare case report.

BACKGROUND: Primary prostate Burkitt's lymphoma is a rare and aggressive condition with a poor prognosis. Its clinical presentation can be challenging to differentiate from benign prostatic hyperplasia. Given the rarity of primary prostate Burkitt's lymphoma, its diagnosis and treatment remain unclear. CASE SUMMARY: This report presents a case of a 57-year-old male with primary prostate Burkitt's lymphoma, initially misdiagnosed as prostatic hyperplasia. This case's operative process, intraoperative findings and postoperative management are discussed in detail. CONCLUSION: Primary prostate lymphoma is difficult to distinguish from other prostate diseases. Holmium laser enucleation of the prostate (HoLEP), a minimally invasive procedure, is crucial in diagnosing and treating this rare disease. Clinicians should remain vigilant and thoroughly combine physical examination, imaging and test results when encountering patients of younger age with small prostate size but a rapid progression of lower urinary tract symptoms. HoLEP is an essential diagnostic and therapeutic tool in managing primary prostate Burkitt's lymphoma.