Research on Laser Cleaning Technology for Aircraft Skin Surface Paint Layer.

In this study, a pulsed laser operating at a wavelength of 1064 nm and with a pulse width of 100 ns was utilized for the removal of paint from the surface of a 2024 aluminum alloy. The experimental investigation was conducted to analyze the influence of laser parameters on the efficacy of paint layer removal from the aircraft skin's surface and the subsequent evolution in the microstructure of the laser-treated aluminum alloy substrate. The mechanism underlying laser cleaning was explored through simulation. The findings revealed that power density and scanning speed significantly affected the quality of cleaning. Notably, there were discernible damage thresholds and optimal cleaning parameters in repetitive frequency, with a power density of 178.25 MW/cm2, scanning speed of 500 mm/s, and repetitive frequency of 40 kHz identified as the primary optimal settings for achieving the desired cleaning effect. Thermal ablation and thermal vibration were identified as the principal mechanisms of cleaning. Moreover, laser processing induced surface dislocations and concentrated stress, accompanied by grain refinement, on the aluminum substrate.

Hepatic arterial infusion chemotherapy with implantable arterial access port for advanced-stage hepatocellular carcinoma: a case report.

Background: Hepatocellular carcinoma (HCC) is a common gastrointestinal malignancy characterized by high incidence rates and a poor prognosis. Common treatment modalities include surgery, ablation, and transarterial chemoembolization (TACE). Hepatic arterial infusion chemotherapy (HAIC) has long been used in the treatment of unresectable liver cancer. In recent years, the combination of anti-angiogenesis therapy and immune checkpoint inhibitors has shown significant advances in the treatment of middle- and advanced-stage liver cancer. This report presents a case of HCC in which sustained benefits are achieved through a combination of HAIC of infusional oxaliplatin, leucovorin, and fluorouracil (FOLFOX), targeted therapy, and immunotherapy. Main body: A 64-year-old male patient was diagnosed with a parenchymal mass in the liver by a three-dimensional color ultrasound one month before admission, prompting consideration of liver cancer. Subsequently, computed tomography (CT) imaging performed at our hospital identified mass shadows in the right lobe of the liver and diffuse nodules throughout the liver, suggesting malignant lesions. Upon admission, the patient presented poor general health and baseline indicators. Following symptomatic treatment, the patient underwent a therapeutic regimen that combined transarterial infusion port FOLFOX-HAIC with Lenvatinib and Sintilimab. This combined treatment resulted in significant liver tumor necrosis and effectively managed the patient's condition. Conclusion: The combined approach of using FOLFO-HAIC transarterial infusion alongside anti-angiogenesis therapy and immune checkpoint inhibitors has shown promising results that provide substantial benefits. This combined regimen has demonstrated the potential to improve treatment compliance among certain patients. Given these encouraging outcomes, further investigation into this combination therapy regimen is warranted to understand better its efficacy and potential broader applications in clinical settings.

Heart and great vessels segmentation in congenital heart disease via CNN and conditioned energy function postprocessing.

PURPOSE: The segmentation of the heart and great vessels in CT images of congenital heart disease (CHD) is critical for the clinical assessment of cardiac anomalies and the diagnosis of CHD. However, the diverse types and abnormalities inherent in CHD present significant challenges to comprehensive heart segmentation. METHODS: We proposed a novel two-stage segmentation approach, integrating a Convolutional Neural Network (CNN) with a postprocessing method with conditioned energy function for pulmonary and aorta. The initial stage employs a CNN enhanced by a gated self-attention mechanism for the segmentation of five primary heart structures and two major vessels. Subsequently, the second stage utilizes a conditioned energy function specifically tailored to refine the segmentation of the pulmonary artery and aorta, ensuring vascular continuity. RESULTS: Our method was evaluated on a public dataset including 110 3D CT volumes, encompassing 16 CHD variants. Compared to prevailing segmentation techniques (U-Net, V-Net, Unetr, dynUnet), our approach demonstrated improvements of 1.02, 1.04, and 1.41% in Dice Coefficient (DSC), Intersection over Union (IOU), and the 95th percentile Hausdorff Distance (HD95), respectively, for heart structure segmentation. For the two great vessels, the enhancements were 1.05, 1.07, and 1.42% in these metrics. CONCLUSION: The outcomes on the public dataset affirm the efficacy of our proposed segmentation method. Precise segmentation of the entire heart and great vessels can significantly aid in the diagnosis and treatment of CHD, underscoring the clinical relevance of our findings.

Delta-sigma modulation supporting the 4194304QAM dual polarization signal at the W-band transmission over a 4.6†km wireless distance.

In this Letter, we propose a dual-polarized coherent millimeter-wave system based on differential delta-sigma modulation (D-DSM) intended for long-distance wireless transmission in the W-band. The proposed system can transmit polarization-division-multiplexed (PDM) D-DSM signals with modulation orders up to 4194304QAM over a wireless channel for 4.6 km at a signal baud rate of 20 G. After 4.6 km of wireless transmission, we successfully achieve a bit error rate (BER) lower than the hard-decision forward error correction (HD-FEC) of 3.8 × 10-3 for 34.51 Gbit/s PDM-524288QAM and a BER lower than the soft-decision forward error correction (SD-FEC) of 4.2 × 10-2 for 32.23 Gbit/s PDM-4194304QAM.

Strategies for the Construction of Benzobicyclo[3.2.1]octane in Natural Product Synthesis.

Benzobicyclo[3.2.1]octane is a cage-like unique motif containing a bicyclo[3.2.1]octane structure fused with at least one benzene ring. It is found in various natural products that exhibit structural complexities and important biological activities. The total synthesis of natural products possessing this challenging structure has received considerable attention, and great advances have been made in this field during the past 15 years. This review summarizes thus far achieved chemical syntheses and synthetic studies of natural compounds featuring the benzobicyclo[3.2.1]octane core. It focuses on strategic approaches constructing the bridged structure, aiming to provide a useful reference for inspiring further advancements in strategies and total syntheses of natural products with such a framework.

The anti-PD-L1/CTLA-4 bispecific antibody KN046 in combination with nab-paclitaxel in first-line treatment of metastatic triple-negative breast cancer: a multicenter phase II trial.

This multicenter, phase II study (NCT03872791) aims to evaluate the efficacy and safety of the anti-PD-L1/CTLA-4 bispecific antibody KN046 combined with nab-paclitaxel in the first-line treatment of patients with metastatic triple-negative breast cancer (TNBC). The primary endpoints included objective response rate (ORR) and duration of response (DoR), and secondary endpoints included progression-free survival (PFS), overall survival (OS) rate, safety, and the correlation of PD-L1 status with clinical efficacy. This trial met pre-specified endpoints. 27 female patients were enrolled sequentially to receive KN046 in two dose levels (3 mg/kg or 5 mg/kg). Among the 25 evaluable patients, the ORR achieved 44.0% (95% CI, 24.4% - 65.1%), and the median DoR was not mature. The median PFS reached 7.33 months (95%CI, 3.68 - 11.07 months), and the median OS was 30.92 months (95%CI, 14.75 - NE months). In PD-L1 positive patients, PFS was 8.61 months (versus 4.73 months) and the 2-year OS rate was 62.5% (versus 57.1%) compared to PD-L1 negative patients. Patients tolerated well the combination therapy. In general, KN046 combined with nab-paclitaxel showed favorable efficacy and survival benefits with tolerable toxicity in the first-line treatment of metastatic TNBC, especially PD-L1 positive, which is worth further investigation.

Polyfluorene Conjugated Polyelectrolytes-Covalently Modified Black Phosphorus Nanosheets for Bioinspired Electronics.

As some of the most promising candidates for constituting bioinspired electronics, polymer memristors with analog-type switching behavior exhibit great potential for synaptic mimicking and neuromorphic computing systems. By using highly soluble conjugated polyelectrolyte poly[9,9-bis(6-(3-methyl-1-imidazolium-yl)hexyl)fluorene]-covalently modified black phosphorus (BP) nanomaterial (BP-PF-NMI+Br-) as the active layer, an electronic device with the BP-PF-NMI+Br- film sandwiched between the aluminum and indium tin oxide electrodes is successfully fabricated. This device exhibits an excellent amount of electricity-dependent memristive performance at a small sweep voltage range of ±1 V. With increasing amount of electricity flowing through the device, the device resistance gradually decreased in a linear pattern. The changes in frequency, amplitude, and duration of voltage pulses do not affect the linear relationship between the amount of electricity passing through the device and the resistance value achieved after each state reached equilibrium at different numbers of the same voltage pulse stimulations. Both the synaptic potentiation/depression and learning/memorizing/forgetting functions of biological systems have been emulated. In contrast to BP-PF-NMI+Br-, the pure PF-NMI+Br--based device shows a write-once-read-many-times effect at the same scanning voltage range, while the BP:PF-NMI+Br- blends exhibit very unstable memristive performances.

A kinetic model for solving a combination optimization problem in ab-initio Cryo-EM 3D reconstruction.

Cryo-Electron Microscopy (cryo-EM) is a widely used and effective method for determining the three-dimensional (3D) structure of biological molecules. For ab-initio Cryo-EM 3D reconstruction using single particle analysis (SPA), estimating the projection direction of the projection image is a crucial step. However, the existing SPA methods based on common lines are sensitive to noise. The error in common line detection will lead to a poor estimation of the projection directions and thus may greatly affect the final reconstruction results. To improve the reconstruction results, multiple candidate common lines are estimated for each pair of projection images. The key problem then becomes a combination optimization problem of selecting consistent common lines from multiple candidates. To solve the problem efficiently, a physics-inspired method based on a kinetic model is proposed in this work. More specifically, hypothetical attractive forces between each pair of candidate common lines are used to calculate a hypothetical torque exerted on each projection image in the 3D reconstruction space, and the rotation under the hypothetical torque is used to optimize the projection direction estimation of the projection image. This way, the consistent common lines along with the projection directions can be found directly without enumeration of all the combinations of the multiple candidate common lines. Compared with the traditional methods, the proposed method is shown to be able to produce more accurate 3D reconstruction results from high noise projection images. Besides the practical value, the proposed method also serves as a good reference for solving similar combinatorial optimization problems.

Dynamic changes of Th1/Th2/Th17 cytokines and hBD-2/3 in erosive oral lichen planus patients saliva before and after prednisone acetate treatment.

Objective: This study aimed to investigate the expression of T helper 1 (Th1)/Th2/Th17- related cytokines and human beta defensins 2 and 3 (hBD-2 and -3) in the saliva of patients with erosive oral lichen planus (EOLP) and to explore their role in the pathogenesis of EOLP and the effects of glucocorticoids on EOLP. Methods: A total of 30 patients with EOLP and 20 age- and sex-matched healthy individuals were included in this study. The patients were treated with prednisone at a dose of 0.4 mg/(kg·d) for 1 week and examined before and after treatment. Unstimulated whole saliva samples were collected to determine the levels of cytokines (interleukin 1 beta [IL-1ß], tumour necrosis factor alpha [TNF]-α, interferon gamma [IFN-γ], IL-4, IL-6, IL-10 and IL-17) by cytometric bead array and those of hBD-2 and -3 b y enzyme-linked immunosorbent assay. In addition, oral rinse samples were collected to detect Candida load. Results: The levels of salivary IL-1ß, IL-6, hBD-2 and hBD-3 were higher and the IFN-γ/IL-4 and IL-1ß/IL-6 ratios were lower in patients with EOLP than in healthy individuals. In patients with EOLP, hBD-2 levels were positively correlated with IFN-γ levels and negatively correlated with IL-17 levels, whereas hBD-3 levels were negatively correlated with IL-17 and IL-10 levels. In addition, the prevalence of EOLP was positively correlated with IL-6 levels and negatively correlated with the IFN-γ/IL-4 ratio. The levels of IL-1ß, TNF-α, IFN-γ, IL-6, hBD-2 and hBD-3 and the IFN-γ/IL-4 ratio decreased after treatment with prednisone for 1 week. The levels of IL-6, hBD-2 and hBD-3 were significantly higher in EOLP patients than in healthy individuals; while TNF-α levels and the IFN-γ/IL-4 ratio were significantly lower in EOLP patients than in healthy individuals. Furthermore, the oral counts of Candida spp. (colony forming unit [CFU]) were negatively correlated with TNF-α levels. Numerical Rating Scale(NRS) and Sign scores decreased in EOLP patients after treatment. Approximately 80 % of patients were effectively treated. Salivary TNF-α levels were significantly higher in the treatment-ineffective group than in the treatment-effective group before treatment with prednisone, and differences in salivary IL-6 levels before and after treatment were significantly higher in the treatment-effective group than in the treatment-ineffective group. Conclusions: High expression of IL-1ß, IL-6, hBD-2 and Th1/Th2 imbalance in saliva may be associated with the pathogenesis of EOLP. IFN-γ/IL-4 balance may serve as a protective factor for EOLP. Glucocorticoids significantly alleviate the symptoms of EOLP and inhibit the expression of Th1/Th2 cytokines.

Post-traumatic stress disorder symptom remission and cognition in a large cohort of civilian women.

BACKGROUND: Post-traumatic stress disorder (PTSD) is associated with cognitive impairments. It is unclear whether problems persist after PTSD symptoms remit. METHODS: Data came from 12 270 trauma-exposed women in the Nurses' Health Study II. Trauma and PTSD symptoms were assessed using validated scales to determine PTSD status as of 2008 (trauma/no PTSD, remitted PTSD, unresolved PTSD) and symptom severity (lifetime and past-month). Starting in 2014, cognitive function was assessed using the Cogstate Brief Battery every 6 or 12 months for up to 24 months. PTSD associations with baseline cognition and longitudinal cognitive changes were estimated by covariate-adjusted linear regression and linear mixed-effects models, respectively. RESULTS: Compared to women with trauma/no PTSD, women with remitted PTSD symptoms had a similar cognitive function at baseline, while women with unresolved PTSD symptoms had worse psychomotor speed/attention and learning/working memory. In women with unresolved PTSD symptoms, past-month PTSD symptom severity was inversely associated with baseline cognition. Over follow-up, both women with remitted and unresolved PTSD symptoms in 2008, especially those with high levels of symptoms, had a faster decline in learning/working memory than women with trauma/no PTSD. In women with remitted PTSD symptoms, higher lifetime PTSD symptom severity was associated with a faster decline in learning/working memory. Results were robust to the adjustment for sociodemographic, biobehavioral, and health factors and were partially attenuated when adjusted for depression. CONCLUSION: Unresolved but not remitted PTSD was associated with worse cognitive function assessed six years later. Accelerated cognitive decline was observed among women with either unresolved or remitted PTSD symptoms.

Development and validation of a combined nomogram for predicting perineural invasion status in rectal cancer via computed tomography-based radiomics.

AIM: This study aimed to create and validate a clinic-radiomics nomogram based on computed tomography (CT) imaging for predicting preoperative perineural invasion (PNI) of rectal cancer (RC). MATERIAL AND METHODS: This study enrolled 303 patients with RC who were divided into training (n = 242) and test datasets (n = 61) in an 8:2 ratio with all their clinical outcomes. A total of 3,296 radiomic features were extracted from CT images. Five machine learning (ML) models (logistic regression (LR)/K-nearest neighbor (KNN)/multilayer perceptron (MLP)/support vector machine (SVM)/light gradient boosting machine (LightGBM)) were developed using radiomic features derived from the arterial and venous phase images, and the model with the best diagnostic performance was selected. By combining the radiomics and clinical signatures, a fused nomogram model was constructed. RESULTS: After using the Mann-Whitney U-test and least absolute shrinkage and selection operator (LASSO) to remove redundant features, the MLP model proved to be the most efficient among the five ML models. The fusion nomogram based on MLP prediction probability further improves the ability to predict the PNI status. The area under the curve (AUC) of the training and test sets was 0.883 and 0.889, respectively, which were higher than those of the clinical (training set, AUC = 0.710; test set, AUC = 0.762) and radiomic models (training set, AUC = 0.840; test set, AUC = 0.834). CONCLUSIONS: The clinical-radiomics combined nomogram model based on enhanced CT images efficiently predicted the PNI status of patients with RC.

Improved Short-Circuit Current and Fill Factor in PM6:Y6 Organic Solar Cells through D18-Cl Doping.

Based on the PM6:Y6 binary system, a novel non-fullerene acceptor material, D18-Cl, was doped into the PM6:Y6 blend to fabricate the active layer. The effects of different doping ratios of D18-Cl on organic solar cells were investigated. The best-performing organic solar cell was achieved when the doping ratio of D18-Cl reached 20 wt%. It exhibited a short-circuit current of 28.13 mA/cm2, a fill factor of 70.25%, an open-circuit voltage (Voc) of 0.81 V, and a power conversion efficiency of 16.08%. The introduction of an appropriate amount of D18-Cl expanded the absorption spectrum of the active layer, improved the morphology of the active layer, reduced large molecular aggregation and defects, minimized bimolecular recombination, and optimized the collection efficiency of charge carriers. These results indicate the critical importance of selecting an appropriate third component in binary systems and optimizing the doping ratio to enhance the performance of ternary organic solar cells.

Combined RNAi of CTTN and FGF2 Modulates Cell Migration, Invasion and G1/S Transition of Hepatocellular Carcinoma through Ras/ERK Signaling Pathway.

BACKGROUND: Most patients with hepatocellular carcinoma (HCC) die of rapid progression and distant metastasis. Gene therapy represents a promising choice for HCC treatment, but the effective targeted methods are still limited. OBJECTIVE: CTTN/cortactin plays a key role in actin polymerization and regulates cytoskeleton remodeling. However, the interaction network of CTTN in HCC is not well understood. METHODS: siRNA was designed for CTTN silencing and Affymetrix GeneChip sequencing was used to obtain the gene profile after CTTN knockdown in the HCC cell line SMMC-7721. Potential interacting genes of CTTN were identified using qRT-PCR. The inhibition on HCC by combined RNA interference (RNAi) of CTTN and fibroblast growth factor 2 (FGF2) was detected. RESULTS: A total of 1,717 significantly altered genes were screened out and 12 potential interacting genes of CTTN were identified. The interaction of CTTN and FGF2 was validated and combined RNAi of CTTN and FGF2 achieved a synergistic effect, leading to better inhibition of HCC cell migration, invasion and G1/S transition than single knockdown of CTTN or FGF2. Mechanistically, combined RNAi of CTTN and FGF2 modulated the Ras/ERK signaling pathway. In addition, the EMT epithelial marker E-cadherin was upregulated while the mesenchymal marker Vimentin and cell cycle protein Cyclin D1 were downregulated after combined RNAi of CTTN and FGF2. Additionally, qRT-PCR and immunohistochemical staining showed that both CTTN and FGF2 were highly expressed in metastatic HCC tissues. CONCLUSION: Combined RNAi of CTTN and FGF2 may be a novel and promising intervention strategy for HCC invasion and metastasis.

Eribulin combined with antiangiogenic agents in women with HER2-negative metastatic breast cancer: a retrospective multicenter study.

Background: The relative lack of specifically targeted agents for HER2-negative metastatic breast cancer (MBC) makes the need for new agents or combination therapies to maximize clinical benefit while reducing toxicity critical. Objectives: To retrospectively analyze the efficacy and safety of eribulin combined with antiangiogenic drugs in the treatment of Chinese women with HER2-negative MBC. Methods: A total of 85 consecutive MBC patients with HER2-negative who were treated with eribulin + antiangiogenic agents between October 2020 and April 2023 in four institutions were retrospectively included in this study. Patients received eribulin 1.4 mg/m2 (day 1 and 8) plus bevacizumab 7.5 mg/kg (day 1, 64 patients) or anlotinib 10 mg daily (day 1-14, 16 patients) or apatinib 250 mg daily (5 patients) on a 21-day cycle until progression or unacceptable toxicity. The primary end-point was progression-free survival (PFS), according to Response Evaluation Criteria in Solid tumors (RECIST) 1.1. Secondary end-points included toxicities, objective response rate (ORR), disease control rate (DCR), and overall survival (OS). Adverse events (AEs) were graded according to Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. Results: The study included 85 HER2-negative MBC patients, with 41 patients (48.2%) in the first to second line group and 44 patients (51.8%) in the greater than or equal to third line group. The median age was 54.0 years. Thirty patients in the first to second line group and 14 patients in the greater than or equal to third line group had triple-negative breast cancer (TNBC). The ORR and DCR were 34.1% (29/85) and 75.3% (64/85). The median PFS (mPFS) of total population was 6.0 months (95% CI: 4.3-7.7), and median OS (mOS) was immature. The mPFS was 7.7 and 4.3 months in the first to second and greater than or equal to third line treatment (p = 0.003), respectively. TNBC patients in first to second line therapy showed a significantly longer PFS (6.5 months versus 2.0 months, p = 0.021) compared to greater than or equal to third line. The incidences of cardiovascular toxicity were 29.4% in grades 1-2 and no grades 3-4. Hematologic toxicity (leukopenia and neutropenia) was the most common grade ⩾3 AEs, and AEs were more common in patients in greater than or equal to third line. Conclusion: The results suggest that eribulin combined with antiangiogenic therapy has a meaningful clinical activity and an acceptable safety profile in HER2-negative MBC.

High quality stealth dicing of sapphire with a picosecond Bessel beam by controlling the polarization direction.

Sapphire is an important substrate material in optoelectronic devices, and it is also widely used as a touch screen panel. In order to achieve high quality cutting of sapphire, the stealth dicing of 500 µm thick sapphire by a picosecond Bessel beam is studied in this paper. The influences of laser polarization direction and process parameters on cutting section roughness were studied. By controlling the laser polarization direction, different crack propagation morphologies were obtained. When the polarization direction was vertical to the cutting path, the crack propagation path was straighter, and the sapphire had better cutting quality. The laser processing parameters, including burst mode, hole spacing, and pulse energy, had a significant impact on the cutting section roughness. When the polarization direction was vertical to the cutting path under the optimal process parameters, the cutting section was uniform and flat, with no recondensable particles, no ripples, and no chamfer, and an 89.7 nm average roughness of the cutting section could be obtained.

PDM-OFDM 1-bit DSM 1024QAM/4096QAM signals at W-band transmission over 4.6-km wireless distance.

In this Letter, we propose the application of delta-sigma modulation (DSM) higher-order quadrature amplitude modulation (QAM) technology in long-distance transmission of W-band wireless communication, and demonstrate, for the first time to the best of our knowledge, the wireless transmission of millimeter wave signals in the W-band based on 1-bit DSM quantization using polarization-division-multiplexed orthogonal frequency division multiplexing (PDM-OFDM) 1024QAM/4096QAM for 4.6 km. We successfully achieved a bit error rate (BER) of 40-Gbit/s PDM-OFDM 1024QAM and 48-Gbit/s PDM-OFDM 4096QAM after 4.6-km wireless transmission, both lower than the soft decision forward error correction (SD-FEC) of 4.2 × 10-2. To the best of our knowledge, this is the first time that up to 4096QAM signals have been quantized and transmitted based on 1-bit DSM in a 4.6-km-long distance W-band millimeter wave system.

Safety and efficacy study of oral metronomic capecitabine combined with pyrotinib in HER2-positive metastatic breast cancer: A phase II trial.

PURPOSE: To analyze the safety and efficacy of orally administered metronomic capecitabine plus pyrotinib in HER2 positive metastatic breast cancer (MBC) patients, we conducted a prospective phase II study with a single-arm design. METHODS: HER2 positive patients received oral metronomic capecitabine 500 mg three times a day and pyrotinib 400 mg per day. The primary endpoint was progression-free survival (PFS). Other endpoints included objective response rate (ORR), overall survival (OS), clinical benefit rate (CBR) and safety. RESULTS: The study included 50 patients with MBC that was HER2-positive, while 1 patient was excluded due to nonstandard medication. The median PFS and OS was 11.9 months (95%CI 8.8-14.6) and 29.3 months (95%CI 24.4-34.8) respectively. ORR was 34.7%, and CBR was 81.6% with 2 CR (4.1%), 15 PR (30.6%) and 23 SD (46.9%). The mPFS in first- or second-line treatment was 12.2 months. The most frequent treatment-related adverse events included hand-foot syndrome, diarrhea, vomiting and nausea. Grade 3 adverse events occurred in 15(30.6%) patients, including hand-foot syndrome (12.2%), diarrhea (12.2%), vomiting (4.1%), and nausea (2.0%). 1 grade 4 adverse event of diarrhea (2.0%) was observed. CONCLUSION: The combination of metronomic capecitabine and pyrotinib is a promising regimen with competitive efficacy and improved tolerability in HER2 positive metastatic breast cancer patients.

Improved survival in patients with isolated liver metastasis at initial diagnosis with surgery at primary and metastatic sites: A population-based study in patients with breast cancer.

BACKGROUND: The aim of this study was to investigate epidemiological characteristics, risk factors, optimal treatment options, and survival outcomes of breast cancer patients with isolated liver metastasis (BCILM). METHODS: Patients with breast cancer (BC) were selected from Incidence-Surveillance, Epidemiology, and End Results (SEER) Research Plus Data, 17 registries between 2010 and 2019. The Kaplan-Meier method and log-rank test were used to compare survival rates between patients who received or did not receive surgery for the primary and liver metastatic sites. Univariate and multivariate analyses were conducted using Cox regression analysis. RESULTS: This study included 17 743 stage IV BC patients, with 3604 (20.3%) patients experiencing liver metastasis at initial diagnosis. Of 3604 liver metastasis patients, 951 were diagnosed with BCILM. The median survival time of patients with BCILM who underwent surgery at the primary site (52.0 months) or distant sites (85.0 months) was significantly longer than that of patients who did not undergo surgery at the primary site (23.0 months) or distant sites (32.0 months). Univariate analysis indicated that age, race, histological grade, molecular subtype, T stage, N stage, surgery of the primary site, surgery to other regional/distant sites, radiotherapy, and chemotherapy were prognostic factors affecting the overall survival (OS) and cancer-specific survival (CSS) of patients with BCILM (p < 0.05). Multivariate analysis suggested that age, race, molecular subtype, T stage, surgery of the primary site, radiotherapy, and chemotherapy were independent prognostic factors. In the BCILM cohort, HR+ /HER2+ patients exhibited the best OS and CSS, followed by HR- /HER2+ , HR+ /HER2- , and HR- /HER2- patients (p < 0.0001; p < 0.0001). CONCLUSION: Surgery at the primary and metastatic sites was associated with better survival in patients with BCILM. HER2+ patients with BCILM had a significantly better prognosis than HER2- patients.

CircEpha5 regulates the synthesis and secretion of androgen in mouse preantral follicles by targeting miR-758-5p.

Circular RNAs are involved in the pathogenesis of various diseases, although its expression pattern and role in polycystic ovary syndrome (PCOS), characterised by hyperandrogenism, are not very clear. This article assessed the circRNAs expression profile in the ovaries of PCOS mice by circRNAs high-throughput sequencing and explored the role of circEpha5 in hyperandrogenism. The results showed that the overexpression of circEpha5 in mouse preantral follicles could increase the expression of Cyp17a1, an androgen synthesis-related gene, which resulted in a higher serum level of testosterone. Dual-luciferase reporter gene studies identified miR-758-5p as a direct target of circEpha5. Consequently, miR-758-5p expression was downregulated upon circEpha5 overexpression. Ectopically expressed miR-758-5p reversed the stimulation effects of circEpha5 on steroidogenesis-related gene expression and testosterone release. Therefore, circEpha5 could sponge miR-758-5p to regulate the expression of Cyp17a1, thereby promoting the synthesis and secretion of androgen in the preantral follicles. This work is contributed to the understanding of the pathogenesis of hyperandrogenemia and lays the foundation for the development of therapeutic targets of PCOS hyperandrogenism.

IMPACT STATEMENTWhat is already known on this subject? PCOS is a complex endocrine and metabolic disorders with hyperandrogenism as the main clinical manifestation. There are a variety of abnormal expression circRNAs in PCOS, however, the relationship between circEpha5 and hyperandrogenism has yet to be fully elucidated.What do the results of this study add? We first found that expression levels of serum circEpha5 were significantly higher in PCOS than in a normal group. Using mouse preantral follicle culture model and the letrozole-induced PCOS mouse model, the mechanism of CircEpha5 regulating androgen secretion was studied.What the implications are of these findings for clinical practice and/or further research? It was revealed that CircEpha5 can absorb miR-758-5p in the sponge to regulate the expression of Cyp17a1, thereby promoting the synthesis and secretion of androgen in preantral follicles, which may become a key target for the screening and treatment of PCOS hyperandrogenism.