Effect and mechanism of C-terminal cysteine on the properties of HEV p222 protein.

Preliminary investigations have demonstrated that the cysteines located at the C-terminus of HEV ORF2 protein exhibits disulfide bonding capability during virus-like particles (VLPs) assembly. However, the effect and mechanism underlying the pairing of disulfide bonds formed by C627, C630, and C638 remains unclear. The p222 protein encompasses C-terminus and serves as a representative of HEV ORF2 to investigate the specific impacts of C627, C630, and C638. The three cysteines were subjected to site-directed mutagenesis and expressed in prokaryotes; Both the mutated proteins and p222 underwent polymerization except for p222A; Surprisingly, only p222 was observed as abundant spherical particles under transmission electron microscope (TEM); Stability and immunogenicity of the p222 exhibited higher than other mutated proteins; LC/MS/MS analysis identified four disulfide bonds in the p222. The novel findings suggest that the three cysteines contribute to structural and functional properties of ORF2 protein, highlighting the indispensability of each cysteine.

Misdiagnosis of lymphoma as vasculitis: A case report.

NK/T-cell lymphoma (NKTCL) is a highly aggressive malignant tumour with a very poor prognosis, which often poses diagnostic difficulties due to the non-specificity of its clinical presentation. NK/T-cell lymphoma with eosinophilic hyperplasia syndrome is extremely rare. This article describes a patient with NKTCL misdiagnosed as vasculitis who presented with sinusitis, abdominal pain, anorexia, and lung shadows. Additionally, the patient exhibited extremely high eosinophilia levels, which led to a further misdiagnosis of eosinophilic granuloma. We describe the clinical features, diagnostic methods and differential diagnosis of lymphoma and highlights the importance of a multidisciplinary approach in accurate diagnosis and treatment.

Spatial transcriptomics reveals prognosis-associated cellular heterogeneity in the papillary thyroid carcinoma microenvironment.

BACKGROUND: Papillary thyroid carcinoma (PTC) is the most common malignant endocrine tumour, and its incidence and prevalence are increasing considerably. Cellular heterogeneity in the tumour microenvironment is important for PTC prognosis. Spatial transcriptomics is a powerful technique for cellular heterogeneity study. METHODS: In conjunction with a clinical pathologist identification method, spatial transcriptomics was employed to characterise the spatial location and RNA profiles of PTC-associated cells within the tissue sections. The spatial RNA-clinical signature genes for each cell type were extracted and applied to outlining the distribution regions of specific cells on the entire section. The cellular heterogeneity of each cell type was further revealed by ContourPlot analysis, monocle analysis, trajectory analysis, ligand-receptor analysis and Gene Ontology enrichment analysis. RESULTS: The spatial distribution region of tumour cells, typical and atypical follicular cells (FCs and AFCs) and immune cells were accurately and comprehensively identified in all five PTC tissue sections. AFCs were identified as a transitional state between FCs and tumour cells, exhibiting a higher resemblance to the latter. Three tumour foci were shared among all patients out of the 13 observed. Notably, tumour foci No. 2 displayed elevated expression levels of genes associated with lower relapse-free survival in PTC patients. We discovered key ligand-receptor interactions, including LAMB3-ITGA2, FN1-ITGA3 and FN1-SDC4, involved in the transition of PTC cells from FCs to AFCs and eventually to tumour cells. High expression of these patterns correlated with reduced relapse-free survival. In the tumour immune microenvironment, reduced interaction between myeloid-derived TGFB1 and TGFBR1 in tumour focus No. 2 contributed to tumourigenesis and increased heterogeneity. The spatial RNA-clinical analysis method developed here revealed prognosis-associated cellular heterogeneity in the PTC microenvironment. CONCLUSIONS: The occurrence of tumour foci No. 2 and three enhanced ligand-receptor interactions in the AFC area/tumour foci reduced the relapse-free survival of PTC patients, potentially leading to improved prognostic strategies and targeted therapies for PTC patients.

CircTBC1D22A inhibits the progression of colorectal cancer through autophagy regulated via miR-1825/ATG14 axis.

Distant metastasis is the main cause of death in patients with colorectal cancer (CRC). A better understanding of the mechanisms of metastasis can greatly improve the outcome of patients with CRC. Accumulating evidence suggests that circRNA plays pivotal roles in cancer progression and metastasis, especially acting as a miRNA sponge to regulate the expression of the target gene. A public database bioinformatics analysis found that miR-1825 was highly expressed in CRC tissues. In this study, miR-1825 was highly expressed in CRC tissues, which was positively correlated with lymph node metastasis and distant metastasis. In vitro and in vivo experiments confirmed that miR-1825 was positively correlated with the proliferation and migration of CRC cells. This event can be inhibited by circTBC1D22A. CircTBC1D22A can directly interact with miR-1825 and subsequently act as a miRNA sponge to regulate the expression of the target gene ATG14, which collectively advances the autophagy-mediated progression and metastasis of CRC.

Study on the cut-off point and the influencing factors of distress in newly diagnosed breast cancer patients.

Objective: Our aim is to investigate the cut-off point of distress and the influencing factors associated with distress in patients with newly diagnosed breast cancer. Methods: A cross-sectional survey of distress was conducted in 167 patients with newly diagnosed breast cancer admitted to the Department of General Surgery of a tertiary care hospital from July 2020 to March 2022. Patients completed the Hospital Anxiety and Depression Scale (HADS) and the Distress Thermometer (DT) questionnaire within 3 days of admission. The HADS ≥15 was used as the gold standard, and the cut-off point of the DT measure was analyzed using the Receiver Operating Characteristic (ROC) curve. The cut-off point obtained by ROC curve analysis was used to analyze the influencing factors of distress in breast cancer patients by univariate and multivariate regression analysis. Results: A total of 167 patients completed the survey, with an average HADS score of 8.43 ± 5.84 and a total HADS score of ≥15 in 37 (22.16%) patients, the mean DT score was 2.96 ± 1.85. ROC curve analysis showed an area under the curve of 0.885, with a maximum Jorden index (0.723) at a DT score of 4, the sensitivity was 100.0% and specificity was 72.3%. There were 73 (43.71%) patients with DT score ≥ 4. Regression analysis showed that insurance/financial problems, dealing with partner problems, tension, bathing/dressing problems, pain, and sleep problems were independent risk factors for l distress in newly diagnosed breast cancer patients. Conclusion: A DT score 4 is the cut-off point for distress in patients with newly diagnosed breast cancer. In clinical practice, target intervention should be carried out according to the risk factors of distress of patients.

Conserved transcription factors NRZ1 and NRM1 regulate NLR receptor-mediated immunity.

Plant innate immunity mediated by the nucleotide-binding leucine-rich repeat (NLR) class of immune receptors plays an important role in defense against various pathogens. Although key biochemical events involving NLR activation and signaling have been recently uncovered, we know very little about the transcriptional regulation of NLRs and their downstream signaling components. Here, we show that the Toll-Interleukin 1 receptor homology domain containing NLR (TNL) gene N (Necrosis), which confers resistance to Tobacco mosaic virus, is transcriptionally induced upon immune activation. We identified two conserved transcription factors, N required C3H zinc finger 1 (NRZ1) and N required MYB-like transcription factor 1 (NRM1), that activate N in an immune responsive manner. Genetic analyses indicated that NRZ1 and NRM1 positively regulate coiled-coil domain-containing NLR- and TNL-mediated immunity and function independently of the signaling component Enhanced Disease Susceptibility 1. Furthermore, NRZ1 functions upstream of NRM1 in cell death signaling, and their gene overexpression induces ectopic cell death and expression of NLR signaling components. Our findings uncovered a conserved transcriptional regulatory network that is central to NLR-mediated cell death and immune signaling in plants.

High-quality assembled and annotated genomes of Nicotiana tabacum and Nicotiana benthamiana reveal chromosome evolution and changes in defense arsenals.

Nicotiana tabacum and Nicotiana benthamiana are widely used models in plant biology research. However, genomic studies of these species have lagged. Here we report the chromosome-level reference genome assemblies for N. benthamiana and N. tabacum with an estimated 99.5% and 99.8% completeness, respectively. Sensitive transcription start and termination site sequencing methods were developed and used for accurate gene annotation in N. tabacum. Comparative analyses revealed evidence for the parental origins and chromosome structural changes, leading to hybrid genome formation of each species. Interestingly, the antiviral silencing genes RDR1, RDR6, DCL2, DCL3, and AGO2 were lost from one or both subgenomes in N. benthamiana, while both homeologs were kept in N. tabacum. Furthermore, the N. benthamiana genome encodes fewer immune receptors and signaling components than that of N. tabacum. These findings uncover possible reasons underlying the hypersusceptible nature of N. benthamiana. We developed the user-friendly Nicomics (http://lifenglab.hzau.edu.cn/Nicomics/) web server to facilitate better use of Nicotiana genomic resources as well as gene structure and expression analyses.

Resveratrol activation of SIRT1/MFN2 can improve mitochondria function, alleviating doxorubicin-induced myocardial injury.

Background: Doxorubicin is a widely used cytotoxic chemotherapy agent for treating different malignancies. However, its use is associated with dose-dependent cardiotoxicity, causing irreversible myocardial damage and significantly reducing the patient's quality of life and survival. In this study, an animal model of doxorubicin-induced cardiomyopathy was used to investigate the pathogenesis of doxorubicin-induced myocardial injury. This study also investigated a possible treatment strategy for alleviating myocardial injury through resveratrol therapy in vitro. Methods: Adult male C57BL/6J mice were randomly divided into a control group and a doxorubicin group. Body weight, echocardiography, surface electrocardiogram, and myocardial histomorphology were measured. The mechanisms of doxorubicin cardiotoxicity in H9c2 cell lines were explored by comparing three groups (phosphate-buffered saline, doxorubicin, and doxorubicin with resveratrol). Results: Compared to the control group, the doxorubicin group showed a lower body weight and higher systolic arterial pressure, associated with reduced left ventricular ejection fraction and left ventricular fractional shortening, prolonged PR interval, and QT interval. These abnormalities were associated with vacuolation and increased disorder in the mitochondria of cardiomyocytes, increased protein expression levels of α-smooth muscle actin and caspase 3, and reduced protein expression levels of Mitofusin2 (MFN2) and Sirtuin1 (SIRT1). Compared to the doxorubicin group, doxorubicin + resveratrol treatment reduced caspase 3 and manganese superoxide dismutase, and increased MFN2 and SIRT1 expression levels. Conclusion: Doxorubicin toxicity leads to abnormal mitochondrial morphology and dysfunction in cardiomyocytes and induces apoptosis by interfering with mitochondrial fusion. Resveratrol ameliorates doxorubicin-induced cardiotoxicity by activating SIRT1/MFN2 to improve mitochondria function.

Tumor Regression upon Intratumoral and Subcutaneous Dosing of the STING Agonist ALG-031048 in Mouse Efficacy Models.

Stimulator of interferon genes (STING) agonists have shown potent anti-tumor efficacy in various mouse tumor models and have the potential to overcome resistance to immune checkpoint inhibitors (ICI) by linking the innate and acquired immune systems. First-generation STING agonists are administered intratumorally; however, a systemic delivery route would greatly expand the clinical use of STING agonists. Biochemical and cell-based experiments, as well as syngeneic mouse efficacy models, were used to demonstrate the anti-tumoral activity of ALG-031048, a novel STING agonist. In vitro, ALG-031048 is highly stable in plasma and liver microsomes and is resistant to degradation via phosphodiesterases. The high stability in biological matrices translated to good cellular potency in a HEK 293 STING R232 reporter assay, efficient activation and maturation of primary human dendritic cells and monocytes, as well as long-lasting, antigen-specific anti-tumor activity in up to 90% of animals in the CT26 mouse colon carcinoma model. Significant reductions in tumor growth were observed in two syngeneic mouse tumor models following subcutaneous administration. Combinations of ALG-031048 and ICIs further enhanced the in vivo anti-tumor activity. This initial demonstration of anti-tumor activity after systemic administration of ALG-031048 warrants further investigation, while the combination of systemically administered ALG-031048 with ICIs offers an attractive approach to overcome key limitations of ICIs in the clinic.

Cardio-oncology in China.

OPINION STATEMENT: Cardio-oncology is going under rapid development in various areas across an increasing number of provinces in China. However there are still a myriad of challenges that need to be overcome in order to ensure its gradual and consistent expansion. The Cardio-Oncology Knowledge Transfer Model (KTM) forms the basis to allow exponential development of effective cardio-oncology services. This would ensure the implementation of precision-based practice while dynamically evolving cardio-oncology to integrate both Western and Chinese medical practices to become an official clinical sub-speciality in its own right in China, for the ultimate benefit of the patient.

The Effects of Angiosome Morphology on Choke Vessels and Flap Necrosis in a Rat Multiterritory Perforator Flap.

BACKGROUND: Although the angiosome concept has been proposed for a long time, very few studies have been done on its morphology. Our study investigated the effects of angiosome morphology on choke vessels and flap necrosis in a rat multiterritory perforator flap. METHODS: Seventy-two male Sprague-Dawley rats were randomly divided into 3 groups (n = 24/group). The flap contained the right iliolumbar, posterior intercostal, and thoracodorsal angiosomes (TDAVs), termed angiosomes I, II, and III, respectively. Only the posterior intercostal artery and iliolumbar vein were preserved in group 1, whereas only the posterior intercostal artery and vein were preserved in group 2, and only the posterior intercostal artery and thoracodorsal vein were preserved in group 3. Distances from angiosome II to angiosome I (II-I), angiosome II to angiosome III (II-III), angiosome I to the caudal side of the flap (I-caudal), and angiosome III to the cranial side of the flap (III-cranial) were measured. Arteriography, flap necrosis, average microvascular density, and vascular endothelial growth factor expression were evaluated. RESULTS: The II-I distance was significantly greater than that of II-III (3.853 ± 0.488 versus 3.274 ± 0.433 cm, P = 0.012), whereas the distance of I-caudal resembled that of III-cranial (1.062 ± 0.237 versus 0.979 ± 0.236 cm, P = 0.442). The iliolumbar and posterior intercostal angiosomes were multidirectional, whereas the TDAV was craniocaudal and unidirectional. Seven days after the operation, the choke arteries had transformed into true anastomotic arteries. Flap necrosis was lowest in group 3, followed by group 2, and highest in group 1 (10.5% ± 2.4% versus 18.3% ± 3.5% versus 25.5% ± 4.6%, P < 0.01), whereas group 3 showed the highest microvascular density and vascular endothelial growth factor expression, in contrast to groups 2 and 1, with the lowest. CONCLUSIONS: The choke vessel adjacent to the craniocaudal and unidirectional TDAV significantly blocked venous return. Increasing venous return may reduce the necrosis.

Psychological outcomes of the systematic interventions based on the stress-induced situation, affective, bodily, and cognitive reactions framework for patients with lung cancer: A randomized clinical trial.

BACKGROUND: Psychological distress is a multi-factorial unpleasant experience of a psychological, social, spiritual, and/or physical nature that may interfere with one's ability to cope effectively with cancer, physical symptoms and treatment. Psychological distress is common and affects the prognosis of cancer patients. Lung cancer accounted for 11.4 % of all new cancer cases and 18 % of all cancer mortality for 36 cancers in 185 countries. The prevalence of distress among Chinese lung cancer patients ranged from 10.1 % to 61.29 %. However, the existing intervention studies on the psychological distress in lung cancer patients are limited and intervention results may be different. OBJECTIVES: To explore the psychological outcomes of a nurse-led systematic intervention program based on the stress-induced situation, affective, bodily, and cognitive reactions framework for patients with lung cancer undergoing operation at anxiety and depression. DESIGN: A randomized clinical trial. SETTING: Thoracic surgery ward in a tertiary hospital in China. PARTICIPANTS: Lung cancer patients undergoing surgery. METHODS: This is a 12-month longitudinal randomized controlled study in a tertiary hospital in China. A total of 240 lung cancer patients were randomly divided into either the control group or the intervention group. The nurse-led systematic intervention contents include psychological education, intervention measures based on the stress-induced situation, affective, bodily, and cognitive reactions framework, issuance of daily lifestyle cards, and regular follow-ups. The Hospital Anxiety and Depression Scale, Functional Assessment of Chronic Illness Therapy-Fatigue Scale, and Satisfaction with Life Scale were used for the baseline assessment within 48 h upon admission. The same assessment was performed respectively at 1, 3, 6 and 12 months after the intervention started. The effects of the systematic interventions on depression, anxiety, fatigue, and life satisfaction were tested by a linear mixed effects model. RESULTS: Overall time-by-group interaction effects were significantly different with regard to anxiety, depression, and fatigue after controlling for the covariates, while a significant time-by-group interaction effect was not found for life satisfaction. Changes for anxiety and depression scores at 6 and 12 months after initiation of the intervention were significantly greater in the intervention group compared with those in the control group (t = 3.046, p = 0.002, t = 3.190, p = 0.001; t = 3.735, p = 0.000, t = 2.979, p = 0.002), whereas scores for fatigue were significantly higher in the intervention group at 6 and 12 months (t = -3.096, p = 0.002, t = -2.784, p = 0.005). CONCLUSION: The systematic intervention program based on the stress-induced situation, affective, bodily, and cognitive reactions framework may effectively relieve anxiety, depression, and fatigue in lung cancer patients undergoing surgery. REGISTRATION: This study was registered on December 22, 2019 with the registration number ChiCTR1900028487, and the date of first recruitment was Jan 5, 2020.

Siglec-9 acts as an immune-checkpoint molecule on macrophages in glioblastoma, restricting T-cell priming and immunotherapy response.

Neoadjuvant immune-checkpoint blockade therapy only benefits a limited fraction of patients with glioblastoma multiforme (GBM). Thus, targeting other immunomodulators on myeloid cells is an attractive therapeutic option. Here, we performed single-cell RNA sequencing and spatial transcriptomics of patients with GBM treated with neoadjuvant anti-PD-1 therapy. We identified unique monocyte-derived tumor-associated macrophage subpopulations with functional plasticity that highly expressed the immunosuppressive SIGLEC9 gene and preferentially accumulated in the nonresponders to anti-PD-1 treatment. Deletion of Siglece (murine homolog) resulted in dramatically restrained tumor development and prolonged survival in mouse models. Mechanistically, targeting Siglece directly activated both CD4+ T cells and CD8+ T cells through antigen presentation, secreted chemokines and co-stimulatory factor interactions. Furthermore, Siglece deletion synergized with anti-PD-1/PD-L1 treatment to improve antitumor efficacy. Our data demonstrated that Siglec-9 is an immune-checkpoint molecule on macrophages that can be targeted to enhance anti-PD-1/PD-L1 therapeutic efficacy for GBM treatment.

Characteristics of patients with incidental eosinophilia admitted to a tertiary hospital in southern China.

Background: The characteristics of patients with eosinophilia are heterogeneous and the outcomes can vary from asymptomatic to severe. Objective: To describe the feature of patients with eosinophilia in a single center. Design: Based on the electronic medical records from Yangjiang People's Hospital in China, the inpatients admitted between June 2018 and February 2021 with measured blood eosinophil counts were evaluated. Methods: Eosinophilia was defined as a peripheral blood eosinophil count of ≥0.5 × 109/L. Differences were compared by eosinophilia severity. The medical records of patients with moderate to severe eosinophilia were reviewed and summarized in terms of examination, diagnoses and management. And these patients were matched with patients without incidental eosinophilia by propensity score and the differences were compared. Results: A total of 7,835 patients with eosinophilia were identified out of 131,566 total inpatients. All types of eosinophilia were most common in males (8.2%; 5,351/65,615), and in patients aged 0-6 years (11.6%; 1,760/15,204), and in the pediatric (10.8%; 1,764/16,336) department, followed by dermatology (10.6%; 123/1,162), Oncology (7.5%; 394/5,239) and Intensive care unit (ICU) (7.4%; 119/1,608). Patients with moderate to severe eosinophilia were more likely to admit to ICU (moderate: 1.3%; severe: 0.50%). In patients with moderate to severe eosinophilia, only 205/621 (33%) had eosinophilia mentioned in their records, and only 63/621 (10.1%) underwent investigations for eosinophilia. The majority of patients with moderate to severe eosinophilia (372/621, 59.9%) had an infectious disease, and little examination (7.4%; 46/621) was taken to identify the cause of eosinophilia, and only 39/621 (6.3%) of patients had a discrete cause of eosinophilia identified. Patients with moderate to severe eosinophilia (24.3%; 151/621) exhibited certain chance to have organ dysfunction. Conclusion: Incidental eosinophilia in inpatients was frequently neglected and less investigated. Multidisciplinary consultation may improve outcomes of inpatients with moderate to severe eosinophilia.

Artificial intelligence-assisted analysis for tumor-immune interaction within the invasive margin of colorectal cancer.

BACKGROUND: In colorectal cancer (CRC), both tumor invasion and immunological analysis at the tumor invasive margin (IM) are significantly associated with patient prognosis, but have traditionally been reported independently. We propose a new scoring system, the TGP-I score, to assess the association and interactions between tumor growth pattern (TGP) and tumor infiltrating lymphocytes at the IM and to predict its prognostic validity for CRC patient stratification. MATERIALS AND METHODS: The types of TGP were assessed in hematoxylin and eosin-stained whole-slide images. The CD3+ T-cells density at the IM was automatically quantified on immunohistochemical-stained slides using a deep learning method. A discovery (N = 347) and a validation (N = 132) cohorts were used to evaluate the prognostic value of the TGP-I score for overall survival. RESULTS: The TGP-I score3 (trichotomy) was an independent prognostic factor, with higher TGP-I score3 associated with worse prognosis in the discovery (unadjusted hazard ratio [HR] for high vs. low 3.62, 95% confidence interval [CI] 2.22-5.90; p < 0.001) and validation cohort (unadjusted HR for high vs. low 5.79, 95% CI 1.84-18.20; p = 0.003). The relative contribution of each parameter to predicting survival was analyzed. The TGP-I score3 had similar importance compared to tumor-node-metastasis staging (31.2% vs. 32.9%) and was stronger than other clinical parameters. CONCLUSIONS: This automated workflow and the proposed TGP-I score could further provide accurate prognostic stratification and have potential value for supporting the clinical decision-making of stage I-III CRC patients.Key messagesA new scoring system, the TGP-I score, was proposed to assess the association and interactions of TGP and TILs at the tumor invasive margin.TGP-I score could be an independent predictor of prognosis for CRC patients, with higher scores being associated with worse survival.TGP-I score had similar importance compared to tumor-node-metastasis staging and was stronger than other clinical parameters.

Biomimetic Nanozymes Suppressed Ferroptosis to Ameliorate Doxorubicin-Induced Cardiotoxicity via Synergetic Effect of Antioxidant Stress and GPX4 Restoration.

Mitochondria-dependent ferroptosis plays an important role in the pathogenesis of doxorubicin (DOX)-induced cardiotoxicity (DIC), which remains a clinical challenge due to the lack of effective interventions. Cerium oxide (CeO2), a representative nanozyme, has attracted much attention because of its antioxidant properties. This study evaluated CeO2-based nanozymes for the prevention and treatment of DIC in vitro and in vivo by adding nanoparticles (NPs), which were synthesized by biomineralization, to the culture or giving them to the mice, and the ferroptosis-specific inhibitor ferrostatin-1 (Fer-1) was used as control. The prepared NPs exhibited an excellent antioxidant response and glutathione peroxidase 4 (GPX4)-depended bioregulation, with the additional merits of bio-clearance and long retention in the heart. The experiments showed that NP treatment could significantly reverse myocardial structural and electrical remodeling, and reduce myocardial necrosis. These cardioprotective therapeutic effects were associated with their ability to alleviate oxidative stress, mitochondrial lipid peroxidation, and mitochondrial membrane potential damage, with a superior efficiency to the Fer-1. The study also found that the NPs significantly restored the expression of GPX4 and mitochondrial-associated proteins, thereby restoring mitochondria-dependent ferroptosis. Therefore, the study provides some insights into the role of ferroptosis in DIC. It also shows that CeO2-based nanozymes could be a promising prevention and treatment candidate as a novel cardiomyocyte ferroptosis protector to mitigate DIC and improve prognosis and quality of life in cancer patients.

Prognosis prediction and risk factors for triple-negative breast cancer patients with brain metastasis: A population-based study.

BACKGROUND: Brain metastasis (BM) in triple-negative breast cancer (TNBC) patients is associated with significant morbidity and mortality. In this research we aimed to develop a nomogram to predict the prognosis of TNBC patients with BMs (TNBC-BM) and explore the potential risk factors. METHODS: We used data from the Surveillance, Epidemiology, and End Results (SEER) database. A prognostic nomogram was built and validated based on patients with BM at newly diagnosed TNBC (nTNBC-BM). Its effect on TNBC patients with BM was also validated in an extended group. The prognostic effect of treatment and risk factors for nTNBC-BM were further tested. RESULTS: A nomogram was constructed and validated to predict overall survival (OS) in TNBC-BM patients. For patients with BM diagnosed at the initial treatment or later course, the C-index (0.707, 0.801, and 0.685 in the training, validation, and extended groups, respectively) and calibration plots showed the acceptable prognostic accuracy and clinical applicability of the model. Surgery on the primary tumor and chemotherapy were found to confer significantly better OS (11 months vs. 4 months; 5 months vs. 3 months, respectively). In addition, advanced tumor/nodal stage and bilateral cancer were associated with a higher risk of nTNBC-BM. CONCLUSION: We developed a sensitive and discriminative nomogram to predict OS in TNBC-BM patients, both at initial diagnosis and the latter course. nTNBC-BM patients may benefit more from surgery and chemotherapy than from radiotherapy. In addition, in the predictive model, TNBC patients harboring advanced tumor/nodal stages and bilateral tumors were more likely to have BM at initial diagnosis.