Breast cancer (BC) is the most common type of cancer found in women. ADP-ribosylation factors (ARFs) are a group of small proteins that bind to GTP and are involved in controlling different cellular functions. The function and evolution of multiple ARFs in BC have remained to be fully elucidated, despite existing studies on this protein family in Homo sapiens and other species. In the present study, a systematic analysis of ARF expression levels in BC tissues compared to normal breast tissues was performed using data from The Cancer Genome Atlas database. The analysis revealed significantly higher expression of ARFs in BC tissues. In addition, the prognostic significance of ARF1 and ARF3-6 expression levels was assessed in patients with BC. Of note, elevated ARF1 expression was associated with reduced rates of distant metastasis-free survival (DMFS), overall survival (OS) and recurrence-free survival (RFS) in affected individuals. Similarly, patients with high expression levels of ARF3 had lower post-progression survival (PPS) rates. In addition, patients with higher ARF4 expression had worse PPS and patients with high ARF5 expression exhibited lower DMFS. Patients with high ARF6 expression had worse DMFS, OS, RFS and predictive power score values. Furthermore, the expression of ARF was found to be strongly linked to the infiltration of various immune cell types, namely dendritic cells, macrophages, neutrophils, CD8+ T cells and B cells. These significant associations offer a solid foundation for the potential utilization of new therapeutic targets and predictive markers for the treatment of BC.

Abstract Background and Purpose： The Anterior Communicating Artery (ACom) is one of the common sites of intracranial aneurysms (IA), and its rupture can severely affect the patient’s life and health. This study pays extensive attention to the morphological and hemodynamic characteristics of the anterior communicating artery aneurysm (ACoA) and further evaluates the causes of ACoA rupture by analyzing these factors. Methods： This study included patient data from January 2017 to October 2023 from the Chinese Multi-central Cerebral Aneurysm Database (CMAD), which contained imaging data for 119 cases. The relationship between clinical characteristics, morphological features, hemodynamic features, and the rupture of the ACoA was explored through traditional logistic regression models, personalized analysis of restrictive cubic spline regression (RCS) models for different factors, and correlation analysis. Results： In multivariable logistics regression (MLR), a history of ischemic stroke, smoking history, aneurysm neck width, and the angle between the anterior cerebral artery A1 segment and the anterior communicating artery (A1-ACom angle) are protective factors. In contrast, the diameter of the anterior communicating artery (ACom) and blood flow velocity are independent risk factors. Correlation analysis shows that there is a significant positive correlation between WFNs score and Hunt-Hess grading, and there is also a significant positive correlation between aneurysm height and aneurysm neck width, and aneurysm height and minimum wall shear stress (WSSmin). In the single-variable restricted cubic regression, the nonlinear model of aneurysm neck width shows some significance in the total threshold. There is significance between aneurysm neck width and a single covariate and all covariates. Conclusions： Factors such as aneurysm neck width, A1-ACom angle, the diameter of the ACom, and blood flow velocity affect the risk of rupture of the ACoA. The aneurysm neck width shows specific nonlinear characteristics in ACoA rupture.

This study investigates the influence of aging-related genes on endometrial cancer, a prominent gynecological malignancy with rising incidence and mortality. By analyzing gene expression differences between cancerous and normal endometrial tissues, 42 aging-related genes were identified as differentially expressed. Utilizing the TCGA-UCEC sample, consensus clustering divided the samples into two molecular subgroups, Aging low and Aging high, based on their expression profiles. These subgroups showed distinct prognoses and survival rates, with the Aging high group associated with DNA repair and cell cycle pathways, and the Aging low group showing suppressed metabolic pathways and increased immune cell infiltration, suggesting a potential for better immunotherapy outcomes. Mutation analysis did not find significant differences in mutation frequencies between the groups, but a high Tumor Mutation Burden (TMB) correlated with better prognosis. A risk score model was also developed, showcasing significant prognostic power. Further analysis of the SIX1 gene revealed its overexpression in cancer cells. Drug sensitivity tests indicated that the low-risk group might respond better to chemotherapy. This research underscores the significance of aging-related genes in endometrial cancer, offering insights into their prognostic value and therapeutic potential, which could lead to personalized treatment approaches and enhanced patient management.

The present study is to investigate the association between T790M status and clinical characteristics of patients with EGFR-sensitive advanced non-small cell lung cancer (NSCLC) who progressed the initial epidermal growth factor receptor tyrosine kinase inhibitors (EGFRTKIs) administration. A total of 167 patients with EGFR-sensitive mutations advanced NSCLC who had successful genetic tests and progressed the initial EGFR-TKI treatment were included in this study retrospectively. The clinical and demographic characteristics of these patients were collected, which were manifested as pathological type, metastasis location, initial biopsy method, initial genetic test specimens, and baseline gene mutations status. Correlation analysis between T790M status and these characteristics was performed and prognostic analysis regarding the different subgroups was carried out accordingly. The prevalence of secondary T790M after resistance to initial EGFR-TKIs among the 167 patients was 52.7%. Correlation analysis indicated that the median progression-free Survival (PFS) to initial EGFR-TKIs >12 months were more likely to develop secondary T790M in univariate analysis. However, the conclusion failed to show statistically significant in multivariate analysis. Additionally, patients with intracranial progression of initial EGFR-TKIs therapy were associated with secondary EGFR-T790M. However, it should be noted that those whose best overall response was partial response (PR) during the EGFR-TKI therapy were relevant to secondary T790M. Furthermore, The median PFS of the initial EGFR-TKIs administration was longer among patients with T790M positive mutation and patients with PR reaction than those without T790M mutation and patients with stable disease (SD), respectively (median PFS: 13.6 vs. 10.9 months, P=0.023) and (median PFS: 14.0 vs. 10.1 months, P=0.001). This retrospective study highlighted the real-world evidence that the best efficacy and intracranial progression with initial EGFR-TKIs therapy among patients with advanced NSCLC might be the promising indicators to predict the occurrence of EGFR-T790M. Patients with PR reaction and T790M positive mutation conferred longer PFS of the initial EGFR-TKIs administration. Also, the conclusion should be confirmed in more patients with advanced NSCLC subsequently.

Large language models (LLMs) have garnered significant attention in the AI domain owing to their exemplary context recognition and response capabilities. However, the potential of LLMs in specific clinical scenarios, particularly in breast cancer diagnosis, treatment, and care, has not been fully explored. This study aimed to compare the performances of three major LLMs in the clinical context of breast cancer. In this study, clinical scenarios designed specifically for breast cancer were segmented into five pivotal domains (nine cases): assessment and diagnosis, treatment decision-making, postoperative care, psychosocial support, and prognosis and rehabilitation. The LLMs were used to generate feedback for various queries related to these domains. For each scenario, a panel of five breast cancer specialists, each with over a decade of experience, evaluated the feedback from LLMs. They assessed feedback concerning LLMs in terms of their quality, relevance, and applicability. There was a moderate level of agreement among the raters (Fleiss' kappa=0.345, P<0.05). Comparing the performance of different models regarding response length, GPT-4.0 and GPT-3.5 provided relatively longer feedback than Claude2. Furthermore, across the nine case analyses, GPT-4.0 significantly outperformed the other two models in average quality, relevance, and applicability. Within the five clinical areas, GPT-4.0 markedly surpassed GPT-3.5 in the quality of the other four areas and scored higher than Claude2 in tasks related to psychosocial support and treatment decision-making. This study revealed that in the realm of clinical applications for breast cancer, GPT-4.0 showcases not only superiority in terms of quality and relevance but also demonstrates exceptional capability in applicability, especially when compared to GPT-3.5. Relative to Claude2, GPT-4.0 holds advantages in specific domains. With the expanding use of LLMs in the clinical field, ongoing optimization and rigorous accuracy assessments are paramount.

Abstract Background Pyrazinamide (PZA) is essential for the treatment of drug-susceptible and drug-resistant tuberculosis (TB), especially multidrug-resistant (MDR) TB, but the condition of PZA resistance (PZA-R) across China is unknown. Our aim is to clarify the genetic mutations of PZA-R and the relationship between PZA-R and MDR-TB in China, from 2007 to 2019. Methods A total of 3202 TB strains with gene sequences results in China were included, among which 1447 strains were sequenced and 1775 were download from the European Nucleic Acid Sequence Database. Drug resistance was investigated by detecting resistance-conferring mutations. A phylogenetic tree was constructed to illustrate the genetic structure of the TB strains. Fisher's exact or Pearson's chi-square tests, as well as logistic regression analysis were used for correlation analysis. Those were calculated by SPSS software. Results All the 3202 strains were divided into four lineages (L1, L2, L3, L4), most belonged to L2 (2745, 85.7%), followed by L4 (443, 13.8%), the rest L1 plus L3 (14, 0.4%). About 45.6% (n = 1459) strains referred to isoniazid resistance (INH-R), 43.4% (n = 1389) rifampicin resistance (RIF-R), and 40.5% (n = 1296) MDR. There were 591 isolates resistant to PZA, among which 96.1% (n = 568) were also MDR. The rate of PZA-R was 43.8% (568/1296) among MDR isolates. The trends of PZA-R fluctuated in accordance with the trends of MDR, INH-R, RIF-R during 2007–2019. Up to 254 kinds of mutations associated with PZA-R were found, with 16.5% (n = 42) isolates harboring ≥ 2 PZA-R associated mutations. Codons 11 (encoding pncA_c.011A &gt; G, n = 30, 11.8%), 76 (encoding pncA_p.Thr76Pro, n = 13, 5.1%), and 139 (encoding pncA_p.Val139Leu, n = 13, 5.1%) were the top three PZA-R associated mutation sites. All PZA-R mutation sites accounting at least 1% were included to analyse the influence of PZA-R on other drug resistance (MDR, INH-R, RIF-R). Finally, three PZA-R related mutations (pncA_p.Val139Ala, pncA_p.Thr47Ala, pncA_p.Leu85Pro) were associated with MDR, four were associate with (pncA_p.Thr76Pro, pncA_p.Val139Ala, pncA_p.Thr47Ala, pncA_p.Leu85Pro) INH-R and none was associated with RIF-R. Conclusion PZA-R especially gene mutation referred to pncA region may promote MDR, this phenomenon mainly associated with the function of PZA-R on INH-R. It is important to consider PZA-R particularly the three associated mutations (pncA region associated mutations) into consideration in treating MDR-TB and explore its mechanism.

The clinical profile of cluster headache may differ among different regions of the world, warranting interest in the data obtained from the initial Chinese Cluster Headache Register Individual Study (CHRIS) for better understanding. We conducted a multicenter, prospective, longitudinal cohort study on cluster headache across all 31 provinces of China, aiming to gather clinical characteristics, treatment approaches, imaging, electrophysiological and biological samples. In total 816 patients were enrolled with a male-to-female ratio of 4.33:1. The mean age at consultation was 34.98 ± 9.91 years, and 24.89 ± 9.77 years at onset. Only 2.33% were diagnosed with chronic cluster headache, and 6.99% had a family history of the condition. The most common bout was one to two times per year (45.96%), lasting two weeks to one month (44.00%), and occurring frequently in spring (76.23%) and winter (73.04%). Of these, 68.50% experienced one to two attacks per day, with the majority lasting one to two hours (45.59%). The most common time for attacks was between 9 am and 12 pm (75.86%), followed by 1 am and 3 am (43.48%). Lacrimation (78.80%) was the most predominant autonomic symptom reported. Furthermore, 39.22% of patients experienced a delay of 10 years or more in receiving a correct diagnosis. Only 35.67% and 24.26% of patients received common acute and preventive treatments, respectively. Due to differences in ethnicity, genetics and lifestyle conditions, CHRIS has provided valuable baseline data from China. By establishing a dynamic cohort with comprehensive multidimensional data, it aims to advance the management system for cluster headache in China.

ABSTRACT Doxorubicin (DOX) is one of the most effective and widely used chemotherapeutic drugs. However, DOX resistance is a critical risk problem for breast cancer treatment. Previous studies have demonstrated that metadherin (MTDH) involves in DOX resistance in breast cancer, but the exact mechanism remains unclear. In this study, we found that glutaminyl-peptide cyclotransferase (QPCT) was a MTDH DOX resistance-related downstream gene in breast cancer. Elevated expression of QPCT was found in the GEPIA database, breast cancer tissue, and breast cancer cells. Clinical data showed that QPCT expression was positively associated with poor prognosis in DOX-treated patients. Overexpression of QPCT could promote the proliferation, invasion and migration, and reduce DOX sensitivity in MCF-7 and MDA-MB-231 cells. Mechanistically, MTDH positively regulates the expressions of NF-κB (p65) and QPCT, and NF-κB (p65) directly regulates the expression of QPCT. Therefore, MTDH/NF-κB (p65)/QPCT signal axis was proposed. Collectively, our findings delineate the mechanism by which the MTDH/NF-κB (p65) axis regulate QPCT signaling and suggest that this complex may play an essential role in breast cancer progression and affect DOX sensitivity.

ABSTRACT Background This study aimed to elucidate the clinical significance and regulatory mechanism of the long non-coding RNA OIP5-AS1 in severe community-acquired pneumonia (SCAP) among paediatric patients. Methods qRT-PCR was used to assess the mRNA levels of OIP5-AS1. ROC curve analysis was used to assess the diagnostic significance of OIP5-AS1. Short-term prognostic significance was evaluated through Kaplan-Meier survival. An in vitro cell model was developed using LPS-induced MRC-5 cells. CCK-8, flow cytometry, and ELISA were conducted to measure cell viability, apoptosis, and inflammatory factor levels. The association between miR-150-5p and PDCD4 was confirmed through DLR assays. Results Elevated OIP5-AS1 were observed in paediatric patients with SCAP, which enabled effective differentiation from healthy individuals. High expression of OIP5-AS1 correlated with reduced survival rates. OIP5-AS1 knockdown attenuated cell viability suppression and the promotion of apoptosis and inflammatory factors induced by LPS. However, this attenuation was reversed by reduced levels of miR-150-5p. miR-150-5p was identified as a target of PDCD4 and OIP5-AS1. Conclusion Increased OIP5-AS1 levels show potential as a valuable diagnostic and prognostic biomarker for paediatric patients with SCAP. This study illustrates its role in regulating cell viability, apoptosis, and the inflammatory response via the miR-150-5p/PDCD4 axis, acting as a ceRNA.

BackgroundPosterior cerebral artery (PCA) aneurysms, though rare, pose treatment challenges. Endovascular therapy is the preferred option, but microsurgery becomes necessary in certain cases. Various microsurgical approaches have been suggested for PCA aneurysms, particularly those at the P2–P3 junction. This study highlights the trans-lateral ventricular approach (TVA) for addressing these complex aneurysms. This study aims to assess the feasibility and safety of the trans-lateral ventricular approach (TVA) for treating high-located complex PCA aneurysms at the P2–P3 junction. The study evaluates both clinical outcomes and anatomical considerations.MethodsTwo cases of PCA aneurysms at the P2–P3 junction were treated using TVA in 2019. Navigation-guided entry via the interparietal sulcus was planned. Ventriculostomy was performed from the cortex to the lateral ventricle’s atrium. Medial atrial floor dissection exposed PCA’s P2–P3 segments. Neuronavigation and ultrasound-aided guidance was used. Anatomical studies on fixed and contrast-perfused specimens refined the approach.ResultsBoth cases saw successful aneurysm clipping. The unruptured aneurysm patient was discharged in 6 days. The poor-grade SAH patient required extended ICU care, moving to rehabilitation with mRS = 4. The unruptured complex aneurysm case exhibited no deficits, returning to work in 3 months. Anatomical dissections validated TVA for high-located P2–P3 junction PCA aneurysms.ConclusionWhile endovascular therapy remains primary, this study demonstrates the viability of navigation-guided TVA for select high-located P2–P3 junction PCA aneurysms. Successes and challenges underscore the importance of patient selection and anatomical awareness.