Abstract Organophosphorus compounds are known to cause toxicity, typically within a few hours following oral exposure, by inhibiting acetylcholinesterase. We report a case in which there was an initial absence of typical muscarinic symptoms, but the patient developed severe typical muscarinic symptoms more than 78 hours after oral ingestion of organophosphate. A 56-year-old male was brought to our hospital complaining of dizziness and nausea 13 hours after ingesting 250ml of 50% fenitrothion. Upon arrival, he exhibited nicotinic symptoms: fasciculations of his tongue and bilateral upper and lower extremities, without any signs of muscarinic symptoms. Because of sudden respiratory depression, he was intubated on the day of admission and received pralidoxime and activated charcoal. Forty-nine hours after admission, he was extubated, as his respiratory function had improved. However, he subsequently developed muscarinic symptoms, including diarrhea, miosis, and bronchorrhea and was therefore intubated again five days after the ingestion. Serum fenitrothion concentrations showed minimal decline between four and five days post-ingestion. Despite resolution of the initial nicotinic symptoms, this patient later developed severe muscarinic symptoms with minimal decrease in the serum fenitrothion concentration during the period. The redistribution from adipose tissue may contribute to the recurrence of the symptoms and delayed drug excretion in organophosphate poisoning.

Aim – GLP-1 and glucagon dual receptor agonists are in clinical development for a range of metabolic conditions including type 2 diabetes and obesity. The cardiovascular actions at these receptors are well studied, however less is known about their combination. The aim was to explore the acute haemodynamic effects of dual agonism at the GLP-1 and glucagon receptor. Methods – Healthy male participants attended randomised, saline-controlled intravenous infusion studies using glucagon [low] (25 ng/kg/min), glucagon [high] (50 ng/kg/min), exenatide (loading dose 50 ng/min for 30 minutes then 25 ng/min) and exenatide:glucagon co-infusion for 120 minutes in Part A (glucagon dose-comparison study) and 60 minutes in Part B (dual-agonism study). Results – In Part A (n=7, median age 21 (IQR 21-32) years), glucagon [high] increased heart rate by 11 bpm (95% CI 4-17 bpm, p<0.01). In Part B (n=12, 24 (22-26) years), exenatide increased heart rate by 4 bpm (95% CI 2-6 bpm, p<0.001). Glucagon [low] increased heart rate by 4 bpm (95% CI 1-7 bpm, p<0.001). Co-infusion of glucagon [low] and exenatide increased heart rate by 7 bpm (95% CI 4-9 bpm, p<0.001) and the rate pressure product by 793 mmHg*bpm (95% CI 460-1127 mmHg*bpm, p<0.001). There were no differences in cardiac output, blood pressure, or heart rate variability. Conclusion – In healthy males, exenatide and glucagon co-infusion acutely increases the rate pressure product, an indirect measure of cardiac work. This increase is driven by an increase in heart rate, rather than any change in systolic blood pressure.

Background: Pulsed electromagnetic field (PEMF) therapy, an often-used supplementary treatment in the horse industry, shows promise in enhancing circulation, reducing inflammation, and supporting cellular repair, however, its effects on equine physiology remain unclear. Limited research, inconsistent protocols, and anecdotal evidence create uncertainty about its efficacy and safety in horses. Given its growing use in equine sports medicine, further studies are needed to standardize its application. Objective: This study evaluates the short-term in vivo effects of PEMF on haematological and biochemical parameters in sport horses. Findings aim to bridge knowledge gaps and guide the safe, effective use of PEMF therapy in equine care. Study design: in vivo experiment, pilot study Methods: Five active sport horses underwent PEMF therapy (Equi Terra, model EMC-230928/1) for five consecutive days using a full-body blanket. The device was set to 1-70 Hz for 20 min., followed by 8 Hz for 15 min. Horses maintained regular training (30-40 min. daily), had ad libitum water access, and a three-meal daily routine. Blood samples were collected pre- and post-treatment to assess 72 haematological, biochemical, and endocrine parameters. Results: Pre- and post-treatment data for each parameter were analysed and compared. While most haematological parameters remained stable, significant alterations were observed in reticulocyte and platelet parameters and haemoglobin levels. Blood biochemistry exhibited greater variability, with notable changes in plasma proteins, bilirubin, uric acid, creatine kinase, creatinine, liver enzymes, and iron-binding capacity. No significant changes were observed in cortisol or thyroxine levels. Conclusion: Whole-body PEMF therapy showed no adverse effects on health or stress response. While most parameters remained unchanged, significant biochemical and haematological changes indicated enhanced physical condition, particularly in muscle function, circulation, and metabolism. These findings suggest that PEMF may support training and warrant further research on its mechanisms and applications.

Effective load balancing and resource distribution strategies are essential for optimizing performance and resource usage in cloud computing. Cloud computing necessitates flexible, dynamic load balancing and resource allocation among multiple goals. Load balancing and resource allocation in cloud computing are complex tasks. The primary goal of dynamic load balancing in cloud computing systems is to enhance resource usage and improve the efficiency of task allocation. The HHO algorithm is accountable for the dynamic allocation of tasks to virtual machines (VMs) according to the distribution of workload and usage of resources. Multiple experimental evaluations and comparisons with alternative load-balancing approaches have proved that the HHO algorithm successfully and efficiently manages dynamic load-balancing. These technological advancements have led to improved reaction times and enhanced resource efficiency. This approach offers a viable and efficient alternative for tackling load-balancing challenges in dynamic scenarios using the cooperative foraging behavior observed in hawks. The proposed approach accounts for the ever-changing demands of cloud applications and dynamically modifies the resource allocation technique. To accomplish this, a multiobjective fitness function is used to cut down on response time and overuse of resources while simultaneously improving resource efficiency. These findings suggest it may help make cloud-based services more efficient and sustainable. The Harris Hawks perform an extensive review of the solution space, wherein they identify the optimal approach for task allocation and adapt to the dynamic workload conditions by employing a process characterized by iterative interactions and positional updates. This approach uses hawks’ collaborative search behavior to dynamically assign tasks to VMs while accounting for load balancing and resource utilization. The proposed methodology can adapt to ever-changing workload demand situations. It employs a multiobjective fitness function to effectively improve key performance indicators such as response time, resource utilization, and efficiency. This work demonstrates how the HHO algorithm could improve the effectiveness and longevity of cloud-based services under changing conditions.

Fresh upper gastrointestinal bleeding (hematemesis),a rare manifestation of retrograde intussusception following classic gastric bypass surgeryNader Moeinvaziri,*1 NaserAfshin1, Nazanin Setayeshpour1,Mohammad Ebrahimi1Laparoscopy research center, Shiraz University of Medical Sciences, Shiraz, Iran*Correspondence to: Nader MoeinvaziriAddress: Department of surgery, Shiraz University of Medical Sciences, Shiraz, IranEmail: nmv1986@yahoo.com Tel: +989177046901

Case Report

Background Hypersensitivity reactions to radiocontrast media (RCM) are rare, but can be life-threatening. The aim of this study was to evaluate the frequency, clinical features and diagnostic test results of radiocontrast media-related hypersensitivity reactions in children. Method Patients aged 0-18 years who underwent computed tomography (CT) and magnetic resonance imaging (MRI) with RCM between 2021-2022 in the Department of Pediatric Radiology at Ankara Bilkent City Hospital were included. The characteristics of the reactions, diagnostic test results, and clinical findings of the patients who required reapplication of radiocontrast media were recorded. Results During the study period, 2336 CT scans were performed with RCM within one year. Immediate reactions developed in 8 patients (0.34%). Iohexol was used in all patients. Skin prick test (SPT) and intradermal test (IDT) performed with suspected RCM were negative in these patients. One patient with urticaria was able to take the same RCM without reaction. Iodine-based RCM was not required in other patients. MRI was performed with gadoteric acid in 1848 patients. Immediate reactions developed in 4 patients (0.22%). No positive results were found in SPT and IDT. One patient with pruritus was able to use the same RCM without reaction. Other patients were not exposed to RCM thereafter. Conclusion In our study, the frequency of immediate reaction with RCM application in paediatric patients was found to be 0.25%. No sensitisation was detected in any of the patients in diagnostic tests.

The phenomenon of antimicrobial resistance (AMR) has reached a critical point, threatening to render traditional antibiotics ineffective and jeopardizing decades of medical progress. At the same time, in the context of the novel coronavirus pneumonia (COVID-19) pandemic, the majority of patients receive antimicrobial treatments that may not be indicated, which may also exacerbate drug-resistant infections globally. Antimicrobial peptides (AMPs) have emerged as a promising alternative, heralding a new era in the fight against drug-resistant infections. This review provides a comprehensive overview of AMPs, demonstrating their potential to revolutionize antimicrobial therapies through unique mechanisms of action that are quite different from those of conventional antibiotics. This review provides insights into the mechanism of action of AMPs and briefly enumerates the clinical applications of AMPs. It focuses on the advances made in peptide engineering to enhance AMPs efficacy, stability and delivery. It also discusses the efficacy of AMPs against pathogens such as methicillin-resistant Staphylococcus aureus (MRSA), mucin-resistant Escherichia coli and multidrug-resistant tuberculosis (MDR-TB). This reveals their potential to overcome current antimicrobial therapy. Furthermore, this review examines the challenges associated with the development of AMPs for clinical use, including issues related to toxicity, stability, and drug resistance. It also outlines strategies to reduce these barriers. Finally, it emphasizes the importance of innovation, interdisciplinary research, and global collaboration to advance AMPs development. Through research, AMPs will be the cornerstone of the ongoing development of antimicrobial therapies, offering hope for addressing the looming threat of drug-resistant infections.

Moisture enabled electric generation generation(MEG) is an innovative green energy technology that converts the chemical potential energy of atmospheric water vapor into electricity. Here, we report a novel zero-dimensional (0D) perovskite-based ionovoltaic device that efficiently harvests ambient moisture to generate electric power, which makes peorvskite be a new kinds of potential MEG. The 0D perovskite, DAP 2PbI 6, (where DAP is 1,3‐bis(ammonium)‐2‐hydroxypropane diiodide.) features a unique hydrogen-bonding network formed between its ammonium (–NH 3 +) and hydroxyl (–OH) group, yielding water stability and remarkable hydrophilicity. Such robust interactions facilitate water adsorption and the subsequent release of hydrogen ions under humid conditions. These protonic species establish an ion gradient, driving a directional current via the ionovoltaic effect. We demonstrated a maximum volumetric power density of 45 mW cm -3—substantially exceeding previously reported values for protein- or carbon-based MEG. Additionally, SEM and AFM analyses confirm the stable of DAP 2PbI 6 upon moisture exposure, while temperature-dependent impedance spectroscopy and theoretical calculations reveal that proton diffusion is the primary mechanism for the observed moisture-driven electricity. These findings underscore the promise of hydrophilic 0D perovskite materials for high-efficiency MEG and pave the way for next-generation sustainable power applications.

Trees in temperate and boreal latitudes synchronize their growth-dormancy cycles with seasonal environmental variations to ensure their survival over the years. Dormancy control is crucial during winter when plants cease growth and establish buds to protect their apical meristems from cold temperatures. To overcome endormancy, initiate bud break, and restore growth, plants must be exposed to a specific duration of chilling, referred to as the chilling requirement, which is species- and ecotype-dependent. In this work, we study the novel roles of two TEMPRANILLO-like genes ( TEML1 and TEML2) in the annual cycle of poplar. We demonstrated that Populus TEML genes are regulated by photoperiod, cold temperatures and the circadian clock, and they play a role in the control of endodormancy. Notably, their function diverges from the role of its Arabidopsis ortholog AtTEM, which regulates FLOWERING LOCUS T (FT) transcription and the photoperiodic flowering transcription. Transcriptomic analysis of endodormant buds during winter revealed that the activation of TEML1 and TEML2 promotes endodormancy release by modulating the expression of endodormancy regulators and growth-promoting genes.

Tsunamis generated by submarine landslides have the potential to cause devastating consequences. A comprehensive understanding of the generation processes and characteristics of landslide-generated tsunamis is essential for improving tsunami hazard prediction and assessment. In this study, we investigated the generation and characteristic of landslide tsunami with numerical modelling constrained by geophysical interpretation in the Xisha Islands, South China Sea. The continuous landsliding processes significantly influence the initial characteristics of tsunami waves. The frequencies of landslide-generated tsunamis exhibit considerable variability due to the continuous landsliding deformation, which is also reflected in the variances of energy spectral density with frequencies. A continuous increase in energy spectral density with frequency leads to a delay in the maximum wave height; while a continuous decrease in energy spectral density with frequency results in longer waves, thereby reducing energy dissipation and producing greater wave heights during initial tsunami propagation in the tsunami generation stage. The wave time series reveals variable coherences at different frequencies in gauges exhibiting an increase/decrease in energy spectral density with frequency. Additionally, phase angle analyses indicate distinct lead/lag relationships that may affect the travel time of tsunami wave. This finding further indicates that tsunami warning system relying solely on a single propagation model to predict tsunamis might be less accurate when estimating both magnitude and arrival time for submarine landslide-generated tsunamis, potentially hindering effective evacuation efforts. This study substantially enhances our understanding on submarine landslide-generated tsunami and will contribute positively to hazard assessment and mitigation strategies.

Mafic eclogites of the Tauern Window, Eastern Alps, preserve vein networks associated with eclogite-facies mineral assemblages. The structural diversity of these veins is encapsulated by two endmembers: Type I tensile veins that exhibit sharp contacts, discordant to the eclogite-facies foliation and Type II fluid segregates with non-planar morphologies. Compositional analysis reveals two main types of mafic eclogite: banded, low-silica and metagabbroic, high-silica compositions. Garnet growth occurred along a prograde P-T path between 2.0 ± 0.15 GPa, 585 ± 15°C and 2.5 ± 0.2 GPa, 630 ± 10°C, consistent with conditions on the slab-wedge interface of modern subduction zones. Dehydration of lawsonite and Na-amphibole released ~5 wt.% H₂O over 20-30°C, creating ~13% transient porosity. In-situ oxygen isotope analysis of quartz-rutile pairs constrains formation temperatures to between 460 °C and 610°C for Type I and II vein structures. Individual veins preserve records of protracted crystallization over ~80°C, suggesting that pockets of undrained fluid persisted in the oceanic crust for 105-106 years during subduction to sub-arc depths. A simple petrological-mechanical model for the blueschist-to-eclogite transition shows that under extremely low permeabilities (10-22 to 10-34 m2), Type I veins may form by tensile failure during periods of high pore fluid pressure, whereas Type II fluid segregates represent accumulations of locally derived fluids during periods of lower fluid pressure. The rate of lawsonite breakdown is intimately linked to hydraulic fracturing and embrittlement of the oceanic crust at depths where intermediate-to-deep seismicity occurs in cold subduction zones.

The interaction between aging oceanic plates and their underlying mantle is a crucial component of the plate tectonic cycle. Sub-lithospheric small-scale convection explains why plates appear not to thicken after a certain age. Yet, many open questions still surround this process. Here, we link grain-scale processes, dynamic models of asthenospheric flow, and seismic observations to gain new insights into the mechanisms of small-scale convection. We present high-resolution 3D geodynamic models of oceanic plate evolution using the community modeling software ASPECT. These simulations use an Earth-like rheology including coupled diffusion and dislocation creep as well as their interplay with evolving olivine grain size. Our models quantify how the balance between diffusion and dislocation creep affects the morphology and temporal stability of small-scale sub-lithospheric convection, including its onset age, the average depth and wavelength of the small-scale convection rolls, and the amplitude of the temperature and grain size anomalies within the rolls. We directly relate these quantities predicted by the dynamic models to geophysical observables through laboratory-derived constitutive relations, converting variations in temperature, pressure, grain size, water content and stable melt fraction to seismic velocity and attenuation. By creating synthetic seismic tomography models of different dynamic scenarios and comparing them to observations from the Pacific OBS Research into Convecting Asthenosphere (ORCA) experiment, we determine the parameter range in which geodynamic models fit these seismic observations. This provides new constraints on oceanic asthenosphere rheology beneath this part of the Pacific Plate, with potentially broad implications for Earth dynamics.

ABSTRACT Pakistan is known to provide shelter and breeding grounds to more than 700 speices of bird belonging to different order of avifauna. The avian diversity is due to a blending in habitats and types of ecozones. These habitations are responsible for the livelihood of species in the ecosystem that not only support a variety of birds but also maintain the overall biodiversity of the country. The current study was conducted in Chitral Gol National Park. A total of 41 Monal Pheasant have been documented from 25 different sites of Chitral Gol National Park through point observation, direct and indirect observation. It was concluded after analyzed data, the Monal Pheasant were more associated to Alpine forest then Mix forest,bare lands, cliffs and rocky edges and showed altitudinal migration with the study area.

A document by Iliana De los Reyes. Click on the document to view its contents.

Polymer insulation is subject to various operating conditions leading to water and electrical tree damage and insulation failure. To address this problem, a dual-responsive LDPE self-healing functional material was prepared by melting grafting in this study. The material system successfully realizes the self-triggered collaborative repair of micro-defects in the electric water tree by precisely manipulating the self-assembly behavior of the grafted monomers under light-water stimulation; meanwhile, the introduction of modified SiO 2 nanoparticles as the matrix filler medium enhances the insulating and thermal conductivity of the composite material. The results show that: the graft modification and nanoparticle filling slightly improve the mechanical properties of LDPE matrix, the breakdown field strength is improved by 15.31%; the filler generated by the graft monomer can effectively fill the micropores, and realize the directional and autonomous repair of micropores damage of the electric water mixing branch; the composite material is capable of self-triggered collaborative repair of the damage of the electric water mixing branch, and the comprehensive performance can be restored to about 95% of the performance of the LDPE.

Medium-entropy alloys (MEAs) are a class of alloys composed of a small number (typically three to four) of principal elements in near-equiatomic ratios. They exhibit a balance between the structural stability of high-entropy alloys (HEAs) and the controllability of conventional alloys, demonstrating excellent mechanical properties, thermal stability, and corrosion resistance. However, the design of MEAs still relies primarily on empirical and trial-and-error methods, making it challenging to accurately predict their phase structures and properties. This study proposes a machine learning-based regression and classification framework to predict the phase structures of quaternary equiatomic MEAs. A dataset of 731 alloy samples was compiled from the literature and categorized into three phase structures: face-centered cubic (FCC, 158 samples), body-centered cubic (BCC, 151 samples), and mixed or amorphous-like structures (none, 422 samples). Seven key features including valence electron concentration (VEC), mixing enthalpy (ΔH mix), atomic size difference (δ), electronegativity difference (Δχ), and maximum, minimum, and average densities—were selected to establish a mathematical model describing the relationship between alloy composition and structure. Three machine learning algorithms—random forest (RFC), support vector machine (SVC), and extreme gradient boosting (XGBoost)—were employed, with hyperparameter optimization conducted using grid search and ten-fold cross-validation. The results indicate that XGBoost is the best-performing model, achieving an accuracy of 0.939 on the test set, outperforming RFC (0.932) and SVC (0.721). Additionally, XGBoost demonstrated superior F1-scores, with 0.947 for the FCC class, 0.923 for BCC, and 0.943 for none, surpassing the other models. These findings confirm that XGBoost effectively identifies key factors influencing phase stability and serves as a reliable predictive tool for the composition optimization of MEAs.

A robust method was developed and validated for determining 107 pesticide residues in livestock and poultry meat. The extraction process utilized acetonitrile in a citric acid buffer environment, followed by clean-up through multi-plug filtration. Separation was achieved using gas chromatography on an HP-5MS capillary column with a programmed temperature gradient, and detection was performed via mass spectrometry in multiple reaction monitoring modes. The results showed that the linear ranges of 107 analytes exhibited strong correlation coefficients, all exceeding 0.9901, with limits of quantification spanning from 1.0 to 15.2 μg/kg. The average recoveries and relative standard deviations for 94 analytes ranging from 70.2% to 120.0% and 4.1% to 15.9%, respectively, at the three different spiked levels. This method was applied to analyze 132 batches of livestock and poultry meat, detecting no pesticides, thereby demonstrating its simplicity, reliability, reproducibility, and suitability for the detection of pesticides in meat samples.

Abstract Introduction : The immune microenvironment is essential in the development of leukoplakia. Which is a potentially precancerous lesion with increased chances of evolving into oral squamous cell carcinoma (OSCC). The immune check point proteins V-domain Ig Suppressor of T-cell Activation (VISTA) and cytotoxic T lymphocyte antigen-4(CTLA-4) are the most important co stimulatory molecule the playa a key role in negative regulation of T cell during process of carcinogenesis. The VISTA and CTLA-4 serves as a emerging new biomarker in early detection and to determine malignant potential of leucoplakia Material and method: Tissue samples from patients with suspected oral malignant lesions were analyzed using immunohistochemistry (IHC). The expression levels of CTLA-4 and VISTA were evaluated using standardized scoring systems. Clinical finding and histopathological grading was established . The correlation between protein expression patterns and clinicopathological parameters was statistically analyzed. Result : VISTA expression varied among the different dysplasia grade with a non-linear relationship observed between VISTA expression and the severity of dysplasia.A distinct progressive rise in CTLA 4 positivity that paralleled the severity of dysplasia, indicating that CTLA 4 expression could serve as a valuable biomarker for evaluating the risk of malignant transformation in oral potentially malignant disorders Keywords: CTLA-4, VISTA, leukoplakia, immune checkpoint proteins, immunohistochemistry, inflammatory check points

Pancreatic Embryonal RhabdomyosarcomaNarendra Pandit1, Durga Neupane2Professor, MS, MCh, FACS, Department of Surgical Gastroenterology, Birat Medical College and Teaching Hospital, Biratnagar, NepalMBBS, Department of Surgery, B.P. Koirala Institute of Health Sciences, Dharan, NepalAuthorsNarendra Pandit (Corresponding author)Email: narendrapandit111@gmail.comDurga NeupaneEmail: neupanedurga26@gmail.comWord count: 500Keywords: pancreas; rhabdomyosarcoma; IHC; embryo

The human-brown bear Ursus arctos conflicts (HBCs) have increased in Hokkaido in recent years. The recent increase in HBCs can be attributed to changes in both the bear and human sides. Brown bears in Hokkaido were added to the list of “Designated Wildlife Species for Control” and the Hokkaido Brown Bear Management Plan (Phase 2) was reviewed in 2024, and the plan includes the concept of active adaptive management, zoning management, and population management when the total population exceeds the region’s acceptable level. HBCs management should be considered as a risk management strategy for natural disasters, consisting of a combination of crisis, exposure, and vulnerability. In an adaptive management scheme, the management policy is determined every few years by each phase based on the annual conflict levels and population levels for each management unit. Zoning management aims for the coexistence of humans and bears through spatial segregation. When implementing management measures, the land is divided into bear habitat as forested areas in the deep mountains, forests around human settlements, human settlements as rural areas, and urban areas. To promote brown bear management in the future, necessary measures and monitoring and its implementation system are discussed based on the concept of risk management and zoning management.

This paper presents a novel cloud-integrated deep learning framework for the real-time core temperature estimation of automotive lithium-ion batteries (LIBs). Accurate core temperature estimation is crucial for rapid thermal management, thermal runaway prediction, and improving battery life and efficiency. The proposed framework integrates physical sensors, a cloud-based data acquisition system, and a Bidirectional Long Short-Term Memory (Bi-LSTM) neural network deployed on both the cloud and a local machine for real-time data collection, core temperature estimation, and visualization. This solution addresses the limitations of traditional temperature monitoring methods, enabling real-time processing and predictive capabilities. The paper discusses the model's architecture, experimental validation, and deployment strategies. The Bi-LSTM network achieves a core temperature estimation accuracy of 0.16°C, even with unknown cell data at varied ambient temperatures and Crates. Unlike existing state-of-the-art studies, this work provides the first demonstration of real-time core temperature estimation with an estimation accuracy of 0.31°C alongside the measurement and visualization for an entire battery module, marking a significant advancement in the field. Additionally, the paper demonstrates real-time decision-making informed by core temperature to prevent overheating and thermal runaway. This is achieved by implementing an automotive-grade CAN communication-based feedback control loop for the charging and discharging of the LIB module. The study also emphasizes the benefits of considering core temperature in improving the response time of thermal management by at least 2 minutes compared to surface temperature-informed control, which is extremely crucial for preventing overheating and protection from thermal runaway. A detailed discussion of computational costs and latency is included, providing a practical reference for realworld applications.

TITLEMedication Use in Medicare Beneficiaries: A Platform for Real-World Pharmacovigilance and Drug Safety Research

Background:Inclisiran, a novel small interfering RNA (siRNA) therapy targeting proprotein convertase subtilisin/kexin type 9 (PCSK9), has demonstrated efficacy in lowering low-density lipoprotein cholesterol (LDL-C). While generally well-tolerated, emerging evidence has highlighted safety concerns, particularly joint-related adverse events (AEs), such as arthralgia. atorvastatin, a commonly prescribed lipid-lowering agent, is also associated with joint-related AEs, leading to concerns about the safety of concomitant use. This study utilized the FDA Adverse Event Reporting System (FAERS) to evaluate inclisiran’s safety profile, with a specific focus on its monotherapy and combination therapy with atorvastatin. Methods :A retrospective pharmacovigilance study was conducted using FAERS data from 2004 to 2024.Advanced signal detection algorithms, including Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Empirical Bayes Geometric Mean (EBGM), and Bayesian Confidence Propagation Neural Network (BCPNN), were employed to detect significant AEs. Data cleaning and standardization were performed using MedDRA terminology. Analyses included signal detection by System Organ Classes (SOCs), Preferred Terms (PTs), drug-drug interaction (DDI) analysis to detect signal. Result:Among 4269 AE reports related to inclisiran, 48.3% were from females, and 31.4% involved individuals ≥65 years. The United States contributed 84.4% of reports, reflecting higher pharmacovigilance reporting in this region.The SOC signal detection indicates that the most frequently reported SOCs included ”general disorders and administration site conditions” (23.78%) and ”musculoskeletal and connective tissue disorders” (16.88%). The PT signal detection indicates Arthralgia was the most reported PT (512 reports; ROR: 5.84, 95% CI: 5.35–6.39), followed by injection site pain and myalgia. The interaction between inclisiran and atorvastatin indicates that Combination therapy was associated with significant signals for musculoskeletal AEs, with synergistic effects noted in joint-related conditions. Conclusion：This comprehensive pharmacovigilance analysis highlights the safety profile of inclisiran, identifying musculoskeletal and injection site-related AEs as primary concerns. The findings emphasize the need for early monitoring during Inclisiran therapy, particularly in at-risk populations such as females, older adults, and those on combination therapy with atorvastatin. Enhanced pharmacovigilance frameworks and real-world evidence are essential to mitigate AE risks and inform clinical practice.