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A variety of state-of-the-art nanovaccines (NVs) combined with immunotherapies have recently been developed to treat malignant tumors, showing promising results. However, immunosuppression in the tumor microenvironment (TME) restrains cytotoxic T cells infiltration and limits the efficacy of immunotherapies in solid tumors. Therefore, tactics for enhancing antigen cross-presentation and reshaping the TME need to be explored to enhance the activity of NV. Here, we developed a photo-enhanceable inflammasome-activating NV (PIN) to achieve precise in situ delivery of a tumor antigen and a hydrophobic small molecule activating the NLRP3-inflammasome pathway. Near-infrared light irradiation promoted PIN accumulation in tumor sites through photo-triggered charge reversal of the nanocarrier. Systematic PIN administration facilitated intratumoral NLRP3 inflammasome activation and antigen cross-presentation in antigen-presenting cells upon light irradiation at tumor sites. Furthermore, PIN treatment triggered immune responses by promoting the production of proinflammatory cytokines and activated of anti-tumor immunity without significant systematic toxicity. Importantly, the PIN enhanced the efficacy of immune checkpoint blockade and supported the establishment of long-term immune memory in mouse models of melanoma and hepatocellular carcinoma. Collectively, this study reports a safe and efficient photoresponsive system for co-delivery of antigens and immune modulators into tumor tissues with promising therapeutic potential.

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Conventional photodynamic therapy (PDT) in cancer treatment needs to utilize oxygen to produce reactive oxygen species to eliminate malignant tissues. However, oxygen consumption in tumor microenvironment exacerbates cancer cell hypoxia and may promote vasculature angiogenesis. Since the mammalian target of rapamycin (mTOR) signaling pathway plays a vital role in endothelial cell proliferation and fibrosis, mTOR inhibitor drugs hold the potential to reverse hypoxia-evoked angiogenesis for improved PDT effect. In this study, a carrier-free nanodrug formulation composed of Torin 1 as mTORC1/C2 dual inhibitor and Verteporfin as a photosensitizer and Yes-associated protein inhibitor is developed. These two drug molecules can self-assemble into stable nanoparticles through π-π stacking and hydrophobic interactions with good long-term stability. The nanodrugs can prompt synergistic apoptosis, combinational anti-angiogenesis, and strong immunogenic cell death effects upon near-infrared light irradiation in vitro. Furthermore, the nanosystem also exhibits improved antitumor effect, anti-cancer immune response, and distant tumor inhibition through tumor microenvironment remodeling in vivo. In this way, the nanodrugs can reverse PDT-elicited angiogenesis and promote cancer immunotherapy to eliminate tumor tissues and prevent metastasis. This nanosystem provides insights into integrating mTOR inhibitors and photosensitizers for safe and effective breast cancer treatment in clinical settings.

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Protein-based drugs have shown unique advantages to treat various diseases in recent years. However, most protein therapeutics in clinical use are limited to extracellular targets with low delivery efficiency. To realize targeted protein delivery, a series of stimuli-triggered nanoparticle formulations have been developed to improve delivery efficiency and reduce off-target release. These smart nanoparticles are designed to release cargo proteins in response to either internal or external stimuli at pathological tissues. In this way, varieties of protein-based drugs including antibodies, enzymes, and pro-apoptotic proteins can be effectively delivered to desired sites for the treatment of cancer, inflammation, metabolic diseases, and so on with minimal side effects. In this review, recent advances in the design of stimuli-triggered nanomedicine for targeted protein delivery in different biomedical applications will be discussed. A deeper understanding of these emerging strategies helps develop more efficient protein delivery systems for clinical use in the future.

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The direct hydrogenation of greenhouse gas CO2 to higher alcohols (C2+OH) provides a new route for the production of high-value chemicals. Due to the difficulty of C-C coupling, the formation of higher alcohols is more difficult compared to that of other compounds. In this review, we summarize recent advances in the development of multifunctional catalysts, including noble metal catalysts, Co-based catalysts, Cu-based catalysts, Fe-based catalysts, and tandem catalysts for the direct hydrogenation of CO2 to higher alcohols. Possible reaction mechanisms are discussed based on the structure-activity relationship of the catalysts. The reaction-coupling strategy holds great potential to regulate the reaction network. The effects of the reaction conditions on CO2 hydrogenation are also analyzed. Finally, we discuss the challenges and potential opportunities for the further development of direct CO2 hydrogenation to higher alcohols.

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Track smoothness has become an important factor in the safe operation of high-speed trains. In order to ensure the safety of high-speed operations, studies on track smoothness detection methods are constantly improving. This paper presents a track irregularity identification method based on CNN-Bi-LSTM and predicts track irregularity through car body acceleration detection, which is easy to collect and can be obtained by passenger trains, so the model proposed in this paper provides an idea for the development of track irregularity identification method based on conventional vehicles. The first step is construction of the data set required for model training. The model input is the car body acceleration detection sequence, and the output is the irregularity sequence of the same length. The fluctuation trend of the irregularity data is extracted by the HP filtering (Hodrick Prescott Filter) algorithm as the prediction target. The second is a prediction model based on the CNN-Bi-LSTM network, extracting features from the car body acceleration data and realizing the point-by-point prediction of irregularities. Meanwhile, this paper proposes an exponential weighted mean square error with priority inner fitting (EIF-MSE) as the loss function, improving the accuracy of big value data prediction, and reducing the risk of false alarms. In conclusion, the model is verified based on the simulation data and the real data measured by the high-speed railway comprehensive inspection train.

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Streaming potential is a type of stress-generated potential in bone that affects the electrical environment of osteocytes and may play a role in bone remodeling. Because the electrical environment around osteocytes has been difficult to measure experimentally until now, a numerical solid-liquid-streaming potential coupling method was proposed to analyze the streaming potential generated by bone deformation in the lacunae and canaliculus network (LCN) of the bone. Using this method, the cellular shear stress caused by liquid flow on the osteocyte surface was first calculated, and the results were consistent with those reported in the literature. Subsequently, the streaming potentials in the LCN caused by bone matrix deformation under an external gait load were calculated numerically. The results showed that the streaming potential increased slowly in the lacuna and relatively rapidly in the canaliculus and that the streaming potential increased with a decrease in the radius or an increase in the length of the canaliculus. The results also showed that relatively large gaps between the lacunae and osteocytes could induce higher streaming potentials under the same loading.

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Purpose: The promotion of angiogenesis is an effective strategy for skin wound repair. While the transplantation of endothelial cells has shown promise in vascularization, the underlying mechanism remains unclear. Recent studies have suggested that transplanted cells undergo apoptosis in a short period and release apoptotic extracellular vesicles (ApoEVs) that may have therapeutic potential. Methods: In this study, we isolated ApoEVs from human umbilical vein endothelial cells (HUVECs) and characterized their properties. In vitro, we assessed the effects of ApoEVs on the proliferation, migration, and differentiation of endothelial cells and fibroblasts. In vivo, we investigated the therapeutic role of ApoEVs-AT in full-thickness skin wounds, evaluating wound closure rate, re-epithelialization, granulation tissue formation, vascularization, scar area, and collagen 3(Col3)/collagen 1(Col 1) ratio. Results: ApoEVs derived from HUVECs displayed typical characteristics. In vitro, ApoEVs significantly enhanced the proliferation, migration, tube formation, and expression of angiogenic-related genes in endothelial cells and slightly promoted the proliferation and migration of fibroblasts. In vivo, ApoEVs improved the wound closure rate, re-epithelialization, the formation of granulation tissue, and vascularization. Besides, ApoEVs reduced scar formation, accompanied by an increase in the Col 3/ Col 1 ratio. Conclusion: Given their abundant source and effectiveness, this study provided a novel approach for angiogenesis in tissue regeneration and deepened the understanding of from death to regeneration.

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The productivity of coal mines is seriously threatened by the combined disasters of gas and coal spontaneous combustion, which have become a common disaster mode. It is unclear how the gas and coal spontaneously combusted in the roof cutting along gob working face. The goal of this study is to identify the distinctive features of combined disasters in gob from two different types of roof cutting along working faces. In these two different types of roof cutting along gob working faces, the paper constructs the permeability model of the gob. The findings demonstrate that the data from the field experiment and the simulation results agree, which validates the simulation's reliability. In contrast to single sided roof cutting along gob working faces, double sided roof cutting along gob working faces clearly has a thinner oxidation zone. Moreover, the oxidation zone of the double side roof cutting along gob working faces is closer to the working face, which is located in the shallow area of the gob 50 m behind the working face. The gas explosion area and the coal spontaneous combustion area are divided by the double side roof cutting along gob working face, which reduces the risk of compound disasters. Important theoretical direction for the prevention and control of gob disasters in the roof cutting along gob working face is provided by the simulation results.

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Background: Invasive micropapillary carcinoma (IMPC) of the breast is a rare subtype of breast cancer with high incidence of aggressive clinical behavior, lymph node metastasis (LNM) and poor prognosis. In the present study, using the Surveillance, Epidemiology, and End Results (SEER) database, we analyzed the clinicopathological characteristics and prognostic factors of IMPC with LNM, and constructed a prognostic nomogram. Methods: We retrospectively analyzed data for 487 breast IMPC patients with LNM in the SEER database from January 2010 to December 2015, and randomly divided these patients into a training cohort (70%) and an internal validation cohort (30%) for the construction and internal validation of the nomogram, respectively. In addition, 248 patients diagnosed with IMPC and LNM at the Fourth Hospital of Hebei Medical University from January 2010 to December 2019 were collected as an external validation cohort. Lasso regression, along with Cox regression, was used to screen risk factors. Further more, the discrimination, calibration, and clinical utility of the nomogram were assessed based on the consistency index (C-index), time-dependent receiver operating characteristic (ROC), calibration curve, and decision curve analysis (DCA). Results: In summary, we identified six variables including molecular subtype of breast cancer, first malignant primary indicator, tumor grade, AJCC stage, radiotherapy and chemotherapy were independent prognostic factors in predicting the prognosis of IMPC patients with LNM (P < 0.05). Based on these factors, a nomogram was constructed for predicting 3- and 5-year overall survival (OS) of patients. The nomogram achieved a C-index of 0.789 (95%CI: 0.759-0.819) in the training cohort, 0.775 (95%CI: 0.731-0.819) in the internal validation cohort, and 0.788 (95%CI: 0.756-0.820) in the external validation cohort. According to the calculated patient risk score, the patients were divided into a high-risk group and a low-risk group, which showed a significant difference in the survival prognosis of the two groups (P<0.0001). The time-dependent ROC curves, calibration curves and DCA curves proved the superiority of the nomogram. Conclusions: We have successfully constructed a nomogram that could predict 3- and 5-year OS of IMPC patients with LNM and may assist clinicians in decision-making and personalized treatment planning.

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Ferroptosis as programmed cell death received considerable attention in cancer research. Recently, studies have associated ferroptosis with photodynamic therapy (PDT) because PDT promotes glutathione (GSH) deletion, glutathione peroxidase 4 (GPX4) degradation, and lipid peroxide accumulation. However, PDT-induced ferroptosis may be potentially prevented by ferroptosis suppressor protein 1 (FSP1). To address this limitation, herein, a novel strategy is developed to trigger ferroptosis by PDT and FSP1 inhibition. For enhancement of this strategy, a photoresponsive nanocomplex, self-assembled by BODIPY-modified poly(amidoamine) (BMP), is utilized to stably encapsulate the inhibitor of FSP1 (iFSP1) and chlorin e6 (Ce6). The nanosystem promotes intracellular delivery, penetration, and accumulation of ferroptosis inducers in tumors with light irradiation. The nanosystem presents high-performance triggering of ferroptosis and immunogenic cell death (ICD) in vitro and in vivo. Importantly, the nanoparticles increase tumor infiltration of CD8+ T cells and further enhance the efficacy of anti-PD-L1 immunotherapy. The study suggests the potential of photo-enhanced synergistic induction of ferroptosis by the photoresponsive nanocomplexes in cancer immunotherapy.

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Heading date is a critical agronomic trait that determines crop yield. Although numerous genes associated with heading date have been identified in rice, the mechanisms involving Small Auxin Up RNA (SAUR) family have not been elucidated. In this study, the biological function of several SAUR genes was initially investigated using the CRISPR-Cas9 technology in the Japonica cultivar Zhonghua11 (ZH11) background. Further analysis revealed that the loss-of-function of OsSAUR56 affected heading date in both NLD (natural long-day) and ASD (artificial short-day). OsSAUR56 exhibited predominant expression in the anther, with its protein localized in both the cytoplasm and nucleus. OsSAUR56 regulated flowering time and heading date by modulating the expression of the clock gene OsGI, as well as two repressors Ghd7 and DTH8. Furthermore, haplotype-phenotype association analysis revealed a strong correlation between OsSAUR56 and heading date, suggesting its role in selection during the domestication of rice. In summary, these findings highlights the importance of OsSAUR56 in the regulation of heading date for further potential facilitating genetic engineering for flowering time during rice breeding. Supplementary Information: The online version contains supplementary material available at 10.1007/s11032-023-01409-w.

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Sensitive and high-throughput analysis of trace elements in volume-limited biological samples is highly desirable for clinical research and health risk assessments. However, the conventional pneumatic nebulization (PN) sample introduction is usually inefficient and not well-suited for this requirement. Herein, a novel high-efficiency (nearly 100% sample introduction efficiency) and low-sample-consumption introduction device was developed and successfully coupled with inductively coupled plasma quadrupole mass spectrometry (ICP-QMS). It consists of a micro-ultrasonic nebulization (MUN) component with an adjustable nebulization rate and a no-waste spray chamber designed based on fluid simulation. The proposed MUN-ICP-QMS could achieve sensitive analysis at a low sampling rate of 10 µL min-1 with an extremely low oxide ratio of 0.25% where the sensitivity is even higher comparing to PN (100 µL min-1). The characterization results indicate that the higher sensitivity of MUN is attributed to the smaller aerosol size, higher aerosol transmission efficiency, and improved ion extraction. In addition, it offers a fast washout (20 s) and reduced sample consumption (as low as 7 µL). The absolute LODs of the studied 26 elements by MUN-ICP-QMS are improved by 1-2 orders of magnitude compared with PN-ICP-QMS. The accuracy of the proposed method was validated by the analysis of human serum, urine, and food-related certified reference materials. Furthermore, preliminary results of serum samples from patients with mental illnesses demonstrated its potential in the field of metallomics.

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To analyze the pollution characteristics and source apportionment of heavy metal pollution in soil of farmland surrounding the Gangue Heap of Coal Mine in Nanchuan, Chongqing, the Nemerow pollution index and Muller index were used. Meanwhile, to investigate the sources and contribution rate of heavy metals in the soil, absolute principal component score-multiple linear regression receptor modeling (APCS-MLR) and positive matrix factorization (PMF) were employed. The results showed higher amounts of Cd, Hg, As, Pb, Cr, Cu, Ni, and Zn in the downstream area than those in the upstream area, and only Cu, Ni, and Zn showed significantly higher amounts in the downstream area than those in upstream area (P<0.05). The comprehensive Nemerow pollution index was as follows:downstream area (1.22)>upstream area (0.95), and the degree of heavy metal pollution was:Cd>Cu>Hg, As, Pb, Cr, Ni, and Zn. The Muller pollution index showed:Cd>As>Cu=Hg>Ni>Zn=Cr>Pb. The pollution source analysis showed that Cu, Ni, and Zn were mainly affected by mining activities such as long-term accumulation of the gangue heap of coal mine, with the contribution rates of APCS-MLR being 49.8%, 94.5%, and 73.2%, respectively. Additionally, PMF contribution rates were 62.8%, 62.2%, and 63.1%, respectively. Cd, Hg, and As were mainly affected by agricultural activities and transportation activities, with APCS-MLR contribution rates of 49.8%, 94.5%, and 73.2% and PMF contribution rates of 62.8%, 62.2%, and 63.1%, respectively. Further, Pb and Cr were mainly affected by natural factors, with APCS-MLR contribution rates of 66.4% and 94.7% and PMF contribution rates of 42.7% and 47.7%, respectively. The results of source analysis were basically consistent between the APCS-MLR and PMF receptor models.

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The stress-generated potential (SGP) of bone is one of the mechanisms affecting bone remodeling including piezoelectricity and streaming potential. To explore the interactions between the piezoelectric and streaming potential, an experimental setup was designed that simultaneously applied a concentrated force and liquid pressure to wet bone. Using this device, the stress-generated potential of wet bone under the two types of loads was measured. The experimental results show that under a constant liquid pressure, the measured potential curves increase over time, and its increasing rate decrease as the concentrated force increase. The measured peak amplitudes of potential decrease as the liquid pressure increase under the same concentrated force whether loading or unloading. To explain the coupling mechanism of the found phenomena, an equivalent model with two voltage sources and three equivalent resistances was established, and the equivalent electrical relationship between the piezoelectric and streaming potential was obtained by analyzing the model. The analysis discussion implies that various factors have influence on the coupling relationship between streaming and piezoelectric potentials, and the factors can be summarized as the changes of the three equivalent resistances caused by piezoelectric and streaming potentials.

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Background: As neoadjuvant chemotherapy is widely used in breast cancer patients, the lymph node ratio has not been fully validated as a prognostic indicator of breast cancer received neoadjuvant chemotherapy. This study was conducted to investigate the prognostic value of lymph node ratio in breast cancer patients received neoadjuvant chemotherapy. Methods: Systematic searches were performed in the PubMed, Embase, and Cochrane Library databases until 15 December 2021 for studies on the association between lymph node ratio and the prognosis of breast cancer after neoadjuvant chemotherapy. Overall survival and disease-free survival were used as outcome events, and hazard ratio was chosen as the parameter to evaluate the correlation. The dose-response relationship was assessed by restricted cubic splines. In the subgroup analyses, which were used to explore potential heterogeneity among the included studies according to study region and sample size. Sensitivity analysis was performed to assess the stability of individual studies, and publication bias was determined with funnel plots, Begg's test, and Egger's test. All statistical analyses were performed using Stata 15.1. Results: A total of 12 studies with 4,864 patients were included in this meta-analysis. In this study, high lymph node ratio was significantly associated with decreased overall survival (HR: 4.74; 95%CI: 3.36-6.67; P < 0.001) and disease-free survival (HR: 4.77; 95%CI: 3.69-6.17; P < 0.001). Moreover, the dose-response meta-analysis showed a linear association between higher lymph node ratio and shorter overall survival and disease-free survival in breast cancer patients after neoadjuvant chemotherapy. Conclusions: The meta-analysis suggested that high lymph node ratio was significantly associated with short overall survival and disease-free survival in breast cancer patients after neoadjuvant chemotherapy. Therefore, lymph node ratio is an independent predictive factor for the prognosis of breast cancer patients after neoadjuvant chemotherapy, which may better refine the cancer staging system.

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Background: There are few studies on young patients with metastatic breast cancer (MBC). This study aims to explore the metastasis pattern and prognosis of young patients with MBC. Methods: A total of 6,336 MBC patients diagnosed in the Surveillance, Epidemiology, and End Results (SEER) database from 2010 to 2015 were selected. They were divided into two age groups: the younger group (≤40 years old) and the older group (>40 years old). χ2 test was used to compare clinicopathological characteristics. Survival differences were compared by Kaplan-Meier analysis. Cox regression models were used to determine the prognostic factors affecting survival. Propensity score matching (PSM) was performed to balance the effects of baseline clinicopathological differences. Results: Finally, 494 patients (7.8%) who are ≤40 years old and 5,842 patients (92.2%) who are >40 years old were included. In the younger group, the proportion of liver metastasis was significantly higher than that in the older group; the proportion of lung metastasis was significantly lower than that of the older group. Kaplan-Meier analysis showed that the younger group had the best prognosis and the older group had the worst. Youth is an independent protective factor for overall survival (OS). In the younger group, liver metastasis had the best prognosis among all metastatic sites, and the HER2-enriched subtype had the best prognosis among all subtypes. Conclusions: The disease in young MBC patients is more aggressive but has a better prognosis, especially in liver metastases and the HER2-enriched subtypes.

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The discovery of long noncoding RNAs (lncRNAs) has filled a great gap in our understanding of posttranscriptional gene regulation in a variety of biological processes related to plant stress responses. However, systematic analyses of the lncRNAs expressed in rice seeds that germinate under cold stress have been elusive. In this study, we performed strand-specific whole transcriptome sequencing in germinated rice seeds under cold stress and normal temperature. A total of 6258 putative lncRNAs were identified and expressed in a stage-specific manner compared to mRNA. By investigating the targets of differentially expressed (DE) lncRNAs of LT-I (phase I of low temperature)/NT-I (phase I of normal temperature), it was shown that the auxin-activated signaling pathway was significantly enriched, and twenty-three protein-coding genes with most of the members of the SAUR family located in chromosome 9 were identified as the candidate target genes that may interact with five lncRNAs. A seed vigor-related lncRNA, SVR, which interplays with the members of the SAUR gene family in cis was eventually identified. The CRISPR/Cas 9 engineered mutations in SVR cause delay of germination. The findings provided new insights into the connection between lncRNAs and the auxin-activated signaling pathway in the regulation of rice seed vigor.

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Autoclaved aerated concrete wallboard (AACW) has been widely used as a building envelope component in the infill walls of frame structures, which has broad prospects for development and utilization. However, the cracking of AACW has become a pressing problem, and this problem needs be solved or relieved effectively. We need an effective control method to reduce the cracking problem of AACW. It is necessary to study the interrelationship between the moisture content and the dry shrinkage of AACW. In this paper, a moisture content test and a drying shrinkage test of AACW were conducted, to understand the effect of the moisture content on the drying shrinkage performance of AACW. In addition, the moisture content of AACW with time was explored, and changes in the dry shrinkage value of AACW with the moisture content of AACW were obtained. According to the results and the conditions and the hypothesis of the test, the drying shrinkage value of AACW increases with time, and the drying shrinkage speed was fast in the early stage and tended to be stable in the later stage. In AACW, the drying shrinkage value and the relative humidity have a notable negative correlation. In addition, there was a positive correlation between the drying shrinkage value and the initial moisture content and the ambient temperature. When the AACW lost water from its initial moisture content to the equilibrium moisture content, the accumulated dry shrinkage value of AACW increased with the water loss. Moreover, a time-varying model of the moisture content and a prediction model of the equilibrium moisture content of AACW were established, and time-varying models of the drying shrinkage value of AACW with different initial moisture contents were proposed. The results provide a scientific basis for the reasonable maintenance and profitable control of drying shrinkage cracking of AACW.

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This study was conducted to investigate the clinicopathological characteristics and prognosis of breast cancer and lung cancer (BC-LC) and provide a theoretical basis for the diagnosis and treatment of BC-LC in clinical work. A retrospective study was conducted on breast cancer (BC) patients in our center from September 2009 to November 2020. The patients were divided into the BC-LC group and the control group. The control group was matched with both, the age at diagnosis and the time of surgery (±1 year). The clinicopathological factors, overall survival (OS), and hazard ratios (HRs) were evaluated by SPSS. A total of 19,807 BC patients were identified, among whom 124 (0.6%) had lung cancer (LC). Larger BC tumor was the only independent risk factor (OR=2.454, p<0.001) for development of LC in BC patients. We found inferior survival in patients with synchronous versus metachronous BC-LC (p=0.008). We also identified combined with hypertension (HR=3.917, p=0.003) was an independent prognostic factor for inferior OS. Therefore, BC patients with larger tumors need close follow-up. Effective prevention and active treatment of hypertension can improve the OS of BC-LC patients.

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