Explore the vast range of titles available.

PCSK9 inhibitors are a novel class of lipid-lowering medications, and numerous clinical studies have confirmed their significant role in improving the progression of chronic kidney disease. However, recent case reports have indicated new evidence regarding their association with acute kidney injury (AKI), with some patients experiencing acute tubular injury after PCSK9 inhibitors use. To clarify the relationship between PCSK9 inhibitors and AKI, we conducted a pharmacovigilance study. Using the Food and Drug Administration Adverse Event Reporting System (FAERS) database from the third quarter of 2015 to the fourth quarter of 2022, a disproportionality analysis was employed to identify adverse events suggestive of AKI after PCSK9 inhibitors use. The drugs of interest included evolocumab and alirocumab. A total of 144,341 adverse event reports related to PCSK9 inhibitors were analyzed, among which 444 cases were suspected of AKI for evolocumab, and 172 cases for alirocumab. Evolocumab had a greater impact on AKI in males (ROR 1.4, 95% CI 1.54-1.69). The ROR and 95% CI for evolocumab and Alirocumab were 0.13 (0.12-0.14) and 0.26 (0.23-0.30) respectively. Further analysis of AKI associated with the concomitant use of PCSK9 inhibitors with cephalosporins, furosemide, torsemide, pantoprazole, omeprazole, and esomeprazole revealed ROR and 95% CI of 0.38 (0.23-0.62), 0.38 (0.31-0.48), 0.18 (0.08-0.38), 0.23 (0.17-0.29), 0.20 (0.16-0.26), and 0.14 (0.10-0.20) respectively. Through the FAERS database, we analyzed the clinical characteristics of AKI associated with PCSK9 inhibitors, exploring its risks. Our findings suggest that PCSK9 inhibitors might have a potential protective effect against AKI and exhibit similar effects when co-administered with other nephrotoxic drugs.

To analyze the clinical characteristics and correlation of Fournier's gangrene induced by sodium-glucose cotransporter protein-2 (SGLT-2) inhibitors, providing references for safe clinical drug use. The CNKI, WanFang, and PubMed databases were searched, and relevant documents were collected and statistically analyzed. The basic information of patients, drug use information, adverse reactions and outcomes were extracted and analyzed. A total of 12 patients (8 males and 4 females) were included, with an average age of 55.6 years (ranging from 34 to 72 years). SGLT-2 inhibitors associated with Fournier's gangrene include empagliflozin (5 cases), dapagliflozin (5 cases), and canagliflozin (2 cases). Among them, 10 cases reported the time of first medication, ranging from 1 month to 6 years for the occurrence of adverse reactions. The most common concomitant drug was metformin (7 cases). Adverse reactions mainly manifested as redness, swelling and pain in the buttocks, perineum, perianal, scrotum and other positions, accompanied by an increased white blood cell count. Following surgery and antibiotic treatment, all patients showed improved. Fournier's gangrene induced by SGLT-2 inhibitors is rare. If patients using SGLT-2 inhibitors are suspected of having Fournier's gangrene, it is recommended to discontinue the drugs immediately and initiate active treatment to ensure clinical safety.

Background N6-methyladenosine (m6A) modification, the most abundant internal methylation of eukaryotic RNA transcripts, is critically implicated in RNA processing. As the largest known component in the m6A methyltransferase complex, KIAA1429 plays a vital role in m6A methylation. However, its function and mechanism in hepatocellular carcinoma (HCC) remain poorly defined. Methods Quantitative PCR, western blot and immunohistochemistry were used to measure the expression of KIAA1429 in HCC. The effects of KIAA1429 on the malignant phenotypes of hepatoma cells were examined in vitro and in vivo. MeRIP-seq, RIP-seq and RNA-seq were performed to identify the target genes of KIAA1429. Results KIAA1429 was considerably upregulated in HCC tissues. High expression of KIAA1429 was associated with poor prognosis among HCC patients. Silencing KIAA1429 suppressed cell proliferation and metastasis in vitro and in vivo. GATA3 was identified as the direct downstream target of KIAA1429-mediated m6A modification. KIAA1429 induced m6A methylation on the 3′ UTR of GATA3 pre-mRNA, leading to the separation of the RNA-binding protein HuR and the degradation of GATA3 pre-mRNA. Strikingly, a long noncoding RNA (lncRNA) GATA3-AS, transcribed from the antisense strand of the GATA3 gene, functioned as a cis -acting element for the preferential interaction of KIAA1429 with GATA3 pre-mRNA. Accordingly, we found that the tumor growth and metastasis driven by KIAA1429 or GATA3-AS were mediated by GATA3. Conclusion Our study proposed a complex KIAA1429-GATA3 regulatory model based on m6A modification and provided insights into the epi-transcriptomic dysregulation in hepatocarcinogenesis and metastasis.

The existence of intratumoral tertiary lymphoid structure (iTLS) has been reported to correlative with favorable clinical outcomes for patients with hepatocellular carcinoma (HCC). However, little is known about the role of peritumoral TLS (pTLS). This study aimed to investigate the prognostic role of pTLS either alone or jointly with iTLS and the potential association with local immune response in HCC. The formation and cellular composition of TLS was evaluated by hematoxylin & eosin and immunohistochemistry. Evaluation of tumor-infiltrating immune cells and formation of germinal center (GC) inside TLS was performed by immunohistochemistry. The gene expression profiles were analyzed by real-time PCR. In a total of 360 patients from two independent cohorts, the pTLS was identified in most, whereas iTLS could be observed in only approximately 30% of HCC specimens. Patients with high pTLS densities were associated with improved outcomes, those present with characteristic morphology of GC, particularly, showing an even better prognosis. The combination of pTLS and iTLS allowed the identification of patients with best prognosis. Tumors with high pTLS density showed significantly increased expression of Th1-, Th17- and immune suppression-related genes, as well as significantly higher infiltration of CD3+, CD8+ and CD20+ cells and lower infiltration of FOXP3+, CD68+ and PD1+ cells. Conclusively, we provide evidence that pTLS is associated with intratumoral immune infiltration, highlighting the dynamic interplay between pTLS and immune cells recruitment. High pTLS density links to a tumor microenvironment with an active immune reaction and improved patient survival and represents a promising prognostic biomarker for HCC.

This study explores how artificial intelligence technologies can enhance the regulatory capacity for legal risks in internet healthcare based on a machine learning (ML) analytical framework and utilizes data from the health insurance portability and accountability act (HIPAA) database. The research methods include data collection and processing, construction and optimization of ML models, and the application of a risk assessment framework. Firstly, the data are sourced from the HIPAA database, encompassing various data types, such as medical records, patient personal information, and treatment costs. Secondly, to address missing values and noise in the data, preprocessing methods such as denoising, normalization, and feature extraction are employed to ensure data quality and model accuracy. Finally, in the selection of ML models, this study experiments with several common algorithms, including extreme gradient boosting (XGBoost), support vector machine (SVM), random forest (RF), and deep neural network (DNN). Each algorithm has its strengths and limitations depending on the specific legal risk assessment task. RF enhances classification performance by integrating multiple decision trees, while SVM achieves efficient classification by identifying the maximum margin hyperplane. DNN demonstrates strong capabilities in handling complex nonlinear relationships, and XGBoost further improves classification accuracy by optimizing decision tree models through gradient boosting. Model performance is evaluated using metrics such as accuracy, recall, precision, F1 score, and area under curve (AUC) value. The experimental results indicate that the DNN model performs excellently in terms of F1 score, accuracy, and recall, showcasing its efficiency and stability in legal risk assessment. The principal component analysis-random forest (PCA+RF) and RF models also exhibit stable performance, making them suitable for various application scenarios. In contrast, the SVM and K-Nearest Neighbor models perform relatively weaker, although they still retain some validity in certain contexts, their overall performance is inferior to deep learning and ensemble learning methods. This study not only provides effective ML tools for legal risk assessment in internet healthcare but also offers theoretical support and practical guidance for future research in this field.

Air pollution caused by particulate matter has significantly improved in China in recent years since the implementation of a series of stringent clean-air regulations. However, surface ozone concentrations have increased, especially in developed city clusters, such as the Beijing-Tianjin-Hebei, Yangtze River Delta, Pearl River Delta, and Sichuan Basin regions. Due to the complexity and nonlinearity of the ozone formation, accurately locating major sources of ozone and its precursors is an important basis for the formulation of cost-effective pollution control strategies. In this paper, the authors systematically summarize the reported results and outcomes of the methods and main conclusions of ozone source apportionment (regions and categories) in China from the published literature, based on observation-based methods and emission-based methods, respectively. The authors aim to provide a comprehensive understanding of ozone pollution and reliable references for the formulation of air pollution prevention policies in China.

With the booming development of electronic information science and 5G communication technology, electromagnetic radiation pollution poses a huge threat and damage to humanity. Developing novel and high-performance electromagnetic wave (EMW) absorbers is an effective method to solve the above issue and has attracted the attention of many researchers. As a typical magnetic material, ferrite plays an important role in the design of high-performance EMW absorbers, and related research focuses on diversified synthesis methods, strong absorption performance, and refined microstructure development. Herein, we focus on the synthesis of ferrites and their composites and introduce recent advances in the high-temperature solid-phase method, sol–gel method, chemical coprecipitation method, and solvent thermal method in the preparation of high-performance EMW absorbers. This review aims to help researchers understand the advantages and disadvantages of ferrite-based EMW absorbers fabricated through these methods. It also provides important guidance and reference for researchers to design high-performance EMW absorption materials based on ferrite.

Introduction Thallium poisoning is a rare occurrence. Therefore, thallium poisoning is easily misdiagnosed and is often accompanied by a series of serious sequelae and can even result in death in severe cases. Here, we report long‐term follow‐up of a case of a patient who was poisoned with thallium on two separate occasions. Methods A 43‐year‐old man was initially misdiagnosed as gastroenteritis, diabetic peripheral neuropathy, and Guillain–Barré Syndrome (GBS) within 21 months. The correct diagnosis was confirmed by blood and urine thallium assays. After Prussian blue treatment, thallium was undetectable in the blood by day 60. Following this investigation, a criminal suspect confessed to two instances of adulterating thallium sulfate in the patient's beverage. A 6‐year follow‐up was performed after discharge, and a comprehensive literature was review. Results We found that the original gastrointestinal symptoms, skin lesions, and hair loss were reversed and had recovered, except for residual neurologic damage, even with long‐term rehabilitation. Discussion Thallium intoxication may have been initially identified if neurologic symptoms had occurred concurrently with gastrointestinal and cutaneous symptoms. Neurologic damage represented the main sequelae of thallium poisoning in our present case report. Thallium poisoning; neurologic outcome; neuroelectrophysiology

The Mesozoic subduction history of the Paleo‐Pacific plate below the East Asian margin remains contentious, in part because the southern part is poorly understood. To address this, we conducted a sediment provenance study to constrain Mesozoic subduction history below West Sarawak, Borneo. A combination of detrital zircon U‐Pb geochronology, heavy minerals, trace element, and bulk rock Nd isotope data were used to identify the tectonic events. The overall maturity of mineral assemblages, dominantly felsic sources, abundant Precambrian‐aged zircons, and low εNd(0) values (average −13.07) seen in Late Triassic sedimentary rocks suggest a period of inactive subduction near Borneo. Slab shallowing subduction occurred between 200 and 170 Ma based on subdued magmatism and tectonic compression across West Sarawak. From c. 170 to 70 Ma there was widespread magmatism and we interpret the Paleo‐Pacific slab steepened. Collectively, we show the Paleo‐Pacific plate subduction had variable slab dip histories in Borneo. Plain Language Summary Modeling studies have shown that the ocean slab underwent periodic shallowing and steepening in the long‐term subduction system. To know the Mesozoic Paleo‐Pacific subduction history of the southern section, we established the subduction process of West Sarawak by studying the provenance of Mesozoic sedimentary rocks. Based on it, we subsequently deduce that west dipping subduction of the Paleo‐Pacific slab underwent periodic shallowing and steepening of slab dip from north to south. Key Points Triassic sediments in West Sarawak were mainly sourced from the craton erosion Paleo‐Pacific slab underwent the Early Jurassic shallowing subduction, followed by slab steepening after the Middle Jurassic in West Borneo The subduction of Paleo‐Pacific plate had variable slab dip histories from West Borneo to northeast China during the Mesozoic

As a novel multiple myeloma (MM) specific antigen, rare is known about the underlying molecular mechanism of MMSA-1 gene in the progression of myeloma. T ranscription factor 4 (TCF4) and MMSA-1 over/down expressed stable U266 cell lines was constructed using lentivirus transfection technique. TCF4 ’s impact on MMSA-1 expression was explored. Overexpressed of MMSA-1’s interaction with RAS protein and its downstream signaling pathways was investigated. Moreover, the interaction changes between overexpressed MMSA-1 protein and bone marrow microenvironment were also detected by examing adhesion molecules and angiogenesis promoting factors using Western Blot. We successfully constructed transcription factor 4 (TCF4) and MMSA-1 over/down expressed stable U266 cell lines (termed TCF4−/+ U266 and MMSA−1−/+ U266). Our result showed that TCF4 could bind with MMSA-1 promoter sequence, greatly up regulate its promotor activity and then improve MMSA-1 expression. Overexpressed MMSA-1 also made a series of changes in U266 cells, including promoting RAS protein expression in cytoplasm, enhancing the interaction between MMSA-1 and RAS , which resulted in hyperactivation of RAS and its downstream signaling pathways including RAF/MEK/ERK and RAF/PI3K/AKT, improving U266 cells’ clonogenicity capacity, changing apoptosis related proteins, reducing the interaction between myeloma cell and bone marrow microenvironment by reducing adhesion molecules expression including HIF-1α, E-cadherin, CXCR4 expression and elevating angiogenesis promoting factors including VEGF, Ang-2 and reducing Ang-1 at the same time. These results suggested MMSA-1 was over expressed in MM cells being regulated by Wnt/β-catenin/TCF4 signaling pathway, which resulted in hyperactivation of downstream RAS/RAF signaling pathway and eventually promote myeloma cells survival and invasion.