Event-related prefrontal activations during online video game playing are modulated by game mechanics, physiological arousal and the amount of daily playing.

There is a trend to study human brain functions in ecological contexts and in relation to human factors. In this study, functional near-infrared spectroscopy (fNIRS) was used to record real-time prefrontal activities in 42 male university student habitual video game players when they played a round of multiplayer online battle arena game, League of Legends. A content-based event coding approach was used to analyze regional activations in relation to event type, physiological arousal indexed by heart rate (HR) change, and individual characteristics of the player. Game events Slay and Slain were found to be associated with similar HR and prefrontal responses before the event onset, but differential responses after the event onset. Ventrolateral prefrontal cortex (VLPFC) activation preceding the Slay onset correlated positively with HR change, whereas activations in dorsolateral prefrontal cortex (DLPFC) and rostral frontal pole area (FPAr) preceding the Slain onset were predicted by self-reported hours of weekly playing (HoWP). Together, these results provide empirical evidence to support the notion that event-related regional prefrontal activations during online video game playing are shaped by game mechanics, in-game dynamics of physiological arousal and individual characteristics the players.

Anion-Cation Competition Chemistry for Comprehensive High-Performance Prussian Blue Analogs Cathodes.

The extensively studied Prussian blue analogs (PBAs) in various batteries are limited by their low discharge capacity, or subpar rate etc., which are solely reliant on the cation (de)intercalation mechanism. In contrast to the currently predominant focus on cations, we report the overlooked anion-cation competition chemistry (Cl-, K+, Zn2+) stimulated by high-voltage scanning. With our designed anion-cation combinations, the KFeMnHCF cathode battery delivers comprehensively superior discharge performance, including voltage plateau >2.0 V (vs. Zn/Zn2+), capacity >150 mAh g-1, rate capability with capacity maintenance above 96 % from 0.6 to 5 A g-1, and cyclic stability exceeding 3000 cycles. We further verify that such comprehensive improvement of electrochemical performance utilizing anion-cation competition chemistry is universal for different types of PBAs. Our work would pave a new and efficient road towards the next-generation high-performance PBAs cathode batteries.

Direct visualization of intraparotid facial nerve assisting in parotid tumor resection.

Precise recognition of the intraparotid facial nerve (IFN) is crucial during parotid tumor resection. We aimed to explore the application effect of direct visualization of the IFN in parotid tumor resection. Fifteen patients with parotid tumors were enrolled in this study and underwent specific radiological scanning in which the IFNs were displayed as high-intensity images. After image segmentation, IFN could be preoperatively directly visualized. Mixed reality combined with surgical navigation were applied to intraoperatively directly visualize the segmentation results as real-time three-dimensional holograms, guiding the surgeons in IFN dissection and tumor resection. Radiological visibility of the IFN, accuracy of image segmentation and postoperative facial nerve function were analyzed. The trunks of IFN were directly visible in radiological images for all patients. Of 37 landmark points on the IFN, 36 were accurately segmented. Four patients were classified as House-Brackmann Grade I postoperatively. Two patients with malignancies had postoperative long-standing facial paralysis. Direct visualization of IFN was a feasible novel method with high accuracy that could assist in recognition of IFN and therefore potentially improve the treatment outcome of parotid tumor resection.

Exploration of the causality of frailty index on psoriasis: A Mendelian randomization study.

BACKGROUND: Frailty is associated with a variety of diseases, but the relationship between frailty and psoriasis remains unclear. METHODS: First, we conducted a two-sample Mendelian randomization based on genome-wide association studies (GWAS) to investigate genetic causality between frailty index and common diseases in dermatology. Inverse variance weighted was used to estimate causality. Second, expression quantitative trait locus (eQTLs) analysis was conducted to identify the genes affected by Single nucleotide polymorphisms (SNPs). Third, we performed function and pathway enrichment, transcriptome-wide association studies (TWAS) analysis based on eQTLs. RESULTS: It was shown that the rise of frailty index could increase the risk of psoriasis (IVW, beta = 0.916, OR = 2.500, 95%CI:1.418-4.408, p = 0.002) through Mendelian randomization (MR), and there was no heterogeneity and pleiotropy. There was no causality between the frailty index and other common diseases in dermatology. We found 31 eQTLs based on strongly correlated SNPs in the causality. TWAS analysis found that the expressions of four genes were closely related to psoriasis, including HLA-DQA1, HLA-DQA2, HLA-DRB1 and HLA-DQB1. CONCLUSION: It suggested that the frailty index had a significant positive causality on the risk of psoriasis, which was well documented by combined genomic, transcriptome, and proteome analyses.

Exploring the Effect of Xiao-Chai-Hu Decoction on Treating Psoriasis Based on Network Pharmacology and Experiment Validation.

BACKGROUND: Psoriasis is a chronic, inflammatory and recurrent skin disease. Xiao-Chai-Hu Decoction (XCHD) has shown good effects against some inflammatory diseases and cancers. However, the pharmacological effect and mechanisms of XCHD on psoriasis are not yet clear. OBJECTIVE: To uncover the effect and mechanisms of XCHD on psoriasis by integrating network pharmacology, molecular docking, and in vivo experiments. METHODS: The active ingredients and corresponding targets of XCHD were screened through Traditional Chinese Medicine Systems Pharmacology Database and Analysis (TCMSP) and Traditional Chinese Medicine Integrated Database (TCMID). Differentially expressed genes (DEGs) of psoriasis were obtained from the gene expression omnibus (GEO) database. The XCHD-psoriasis intersection targets were obtained by intersecting XCHD targets, and DEGs were used to establish the "herb-active ingredient-target" network and Protein-Protein Interaction (PPI) Network. The hub targets were identified based on the PPI network by Cytoscape software. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were performed next. Molecular docking was executed via AutoDockTools-1.5.6. Finally, in vivo experiments were carried out further to validate the therapeutic effects of XCHD on psoriasis. RESULTS: 58 active components and 219 targets of XCHD were screened. 4 top-active components (quercetin, baicalein, wogonin and kaempferol) and 7 hub targets (IL1B, CXCL8, CCND1, FOS, MMP9, STAT1 and CCL2) were identified. GO and KEGG pathway enrichment analyses indicated that the TNF signaling pathway, IL-17 signaling pathway and several pathways were involved. Molecular docking results indicated that hub genes had a good affinity to the corresponding key compounds. In imiquimod (IMQ)-induced psoriasis mouse models, XCHD could significantly improve psoriasis-like skin lesions, downregulate KRT17 and Ki67, and inhibit inflammation cytokines and VEGF. CONCLUSION: XCHD showed the therapeutic effect on psoriasis by regulating keratinocyte differentiation, and suppressing inflammation and angiogenesis, which provided a theoretical basis for further experiments and clinical research.

Discovery of novel pyrrolo[2,3-d]pyrimidines as potent menin-mixed lineage leukemia interaction inhibitors.

To interfere the Menin-MLL interaction using small molecular inhibitors has been shown as new treatment of several special hematological malignancies. Herein, a series of Menin-MLL interaction inhibitors with pyrrolo[2,3-d]pyrimidine scaffold were designed, synthesized and evaluated. Among them, compound A6 exhibited potent binding affinity with an IC50 value of 0.38 µM, and strong anti-proliferative activity against MV4-11 cells with an IC50 value of 1.07 µM. Further study showed A6 reduced the transcriptional levels of HOXA9 and MEIS1 genes. Moreover, A6 induced cellular apoptosis, arrested the cell cycle in G0/G1 phase, and reversed the differentiation arrest in a concentration-dependent manner. This study suggested compound A6 was as a novel potent Menin-MLL interaction inhibitor, and it proved that introduction of 4-amino pyrrolo[2,3-d]pyrimidine to occupy the P10 hydrophobic pocket was new idea for design of novel Menin-MLL interaction inhibitors.

Duplex-Hierarchy Representation Learning for Remote Sensing Image Classification.

Remote sensing image classification (RSIC) is designed to assign specific semantic labels to aerial images, which is significant and fundamental in many applications. In recent years, substantial work has been conducted on RSIC with the help of deep learning models. Even though these models have greatly enhanced the performance of RSIC, the issues of diversity in the same class and similarity between different classes in remote sensing images remain huge challenges for RSIC. To solve these problems, a duplex-hierarchy representation learning (DHRL) method is proposed. The proposed DHRL method aims to explore duplex-hierarchy spaces, including a common space and a label space, to learn discriminative representations for RSIC. The proposed DHRL method consists of three main steps: First, paired images are fed to a pretrained ResNet network for extracting the corresponding features. Second, the extracted features are further explored and mapped into a common space for reducing the intra-class scatter and enlarging the inter-class separation. Third, the obtained representations are used to predict the categories of the input images, and the discrimination loss in the label space is minimized to further promote the learning of discriminative representations. Meanwhile, a confusion score is computed and added to the classification loss for guiding the discriminative representation learning via backpropagation. The comprehensive experimental results show that the proposed method is superior to the existing state-of-the-art methods on two challenging remote sensing image scene datasets, demonstrating that the proposed method is significantly effective.

METTL3-Mediated m6A Modification Regulates the Osteogenic Differentiation through LncRNA CUTALP in Periodontal Mesenchymal Stem Cells of Periodontitis Patients.

Objective: Periodontitis is a chronic inflammatory disease that causes loss of periodontal support tissue. Our objective was to investigate the mechanism by which METTL3-mediated N6-methyladenosine modification regulates the osteogenic differentiation through lncRNA in periodontal mesenchymal stem cells in patients with periodontitis (pPDLSCs). Material and Methods. We carried out a series of experiments, including methylated RNA immunoprecipitation-PCR, quantitative real-time polymerase chain reaction, and western blotting. The expressions of alkaline phosphatase (ALP), Runx2, Col1, Runx2 protein level, ALP staining, and Alizarin red staining were used to demonstrate the degree of osteogenic differentiation. Results: We found that METTL3 was the most significantly differentially expressed methylation-related enzyme in pPDLSCs and promoted osteogenic differentiation of pPDLSCs. METTL3 regulated the stability and expression of lncRNA CUTALP, while lncRNA CUTALP promoted osteogenic differentiation of pPDLSCs by inhibiting miR-30b-3p. At different time points of osteogenic differentiation, lncRNA CUTALP expression was positively correlated with Runx2, while miR-30b-3p showed the opposite pattern. The attenuated osteogenic differentiation induced by METTL3 knockdown was recovered by lncRNA CUTALP overexpression. The attenuated osteogenic differentiation induced by lncRNA CUTALP knockdown could be reversed by the miR-30b-3p inhibitor. Conclusions: In summary, METTL3/lncRNA CUTALP/miR-30b-3p/Runx2 is a regulatory network in the osteogenic differentiation of pPDLSCs.

Sex differences in alterations of brain functional network in tobacco use disorder.

INTRODUCTION: Many studies have found sex differences in alterations of brain function in cigarette smoking adults from the perspective of functional activity or connectivity. However, no studies have systematically found different alteration patterns in brain functional topology of cigarette smoking men and women from three perspectives: nodal and network efficiency, and modular connections. METHODS: Fifty-six tobacco use disorder (TUD) participants (25 women) and 66 non-TUD participants (28 women) underwent a resting-state functional magnetic resonance imaging scan. The whole-brain functional networks were constructed and a two-way analysis of covariance with false discovery rate correction (q < 0.05) were performed to investigate whether men and women TUD participants had different alterations in the topological features at global, modular and nodal levels. RESULTS: Compared to non-TUD participants, men but not women TUD participants showed significantly lower global efficiency (lower inter-modular connections between the visual and executive control, between the visual and subcortical modules did not pass the correction) and significantly lower nodal global efficiency in the right superior occipital gyrus, bilateral fusiform gyrus, the right pallidum, right putamen, the bilateral paracentral lobule, the postcentral gyrus, and lower nodal local efficiency in the left paracentral lobule. CONCLUSIONS: Men and women TUD participants have different topological properties of brain functional network, which may contribute to our understanding of neural mechanisms underlying sex differences in TUD. IMPLICATIONS: Compared to non-TUD participants, we found men but not women TUD participants with significantly lower network metrics at global, modular and nodal level, which could improve our understanding of neural mechanisms underlying sex differences in TUD and lay a solid foundation for future sex-based TUD prevention and treatment.

Redox-active phytic acid-based self-assembled hybrid material for enhanced uranium adsorption from highly acidic solution.

Achieving efficient uranium adsorption from highly acidic wastewater is still considered challenging. Here, an inorganic-organic hybridized self-assembly material (rPFE-10) with redox activity was constructed by phytic acid (PA), ethylenediamine (EDA), and Fe(II) via a facile one-pot route, and further applied for U(VI) removal. In the static adsorption experiment, rPFE-10 achieved the maximum U(VI) adsorption capacity of 717.1 mg/g at the optimal pH of 3.5. It also performed preeminently in a highly acidic condition of pH = 1.0, with the highest adsorption capacity of 551.2 mg/g and an equilibrium time of 30 min. Moreover, rPFE-10 exhibited a pH-responsive adsorption selectivity for U(VI) and An-Ln (S(U(VI)) and S(An-Ln)), which increased to 69 % and 94 % respectively as pH decreased from 3.0 to 1.0. Additionally, the spectral analysis revealed a reconstruction mechanism induced by multiple synergistic adsorption, in which U(VI) exchange with EDA+/2+ and Fe2+/3+ and earned suitable coordination geometry and ligand environment to coordinate with PA (mainly P-OH), while partial U(VI) is reduced by Fe(II) in framework. This work not only highlights the facile strategy for enhanced U(VI) retention in highly acidic solution, but expands the potential application of supramolecular self-assembly material in treatment of nuclear wastewater.

Investigation of GPR143 as a promising novel marker for the progression of skin cutaneous melanoma through bioinformatic analyses and cell experiments.

BACKGROUND: Skin cutaneous melanoma (SKCM) is an aggressive and life-threatening skin cancer. G-protein coupled receptor 143 (GPR143) belongs to the superfamily of G protein-coupled receptors. METHODS: We used the TCGA, GTEx, CCLE, and the Human Protein Atlas databases to examine the mRNA and protein expression of GPR143. In addition, we performed a survival analysis and evaluated the diagnostic efficacy using the Receiver-Operating Characteristic (ROC) curve. Through CIBERSORT, R programming, TIMER, Gene Expression Profiling Interactive Analysis, Sangerbox, and Kaplan-Meier plotter database analyses, we explored the relationships between GPR143, immune infiltration, and gene marker expression of immune infiltrated cells. Furthermore, we investigated the proteins that potentially interact with GPR143 and their functions using R programming and databases including STRING, GeneMANIA, and GSEA. Meanwhile, the cBioPortal, UALCNA, and the MethSurv databases were used to examine the genomic alteration and methylation of GPR143 in SKCM. The Connectivity Map database was used to discover potentially effective therapeutic molecules against SKCM. Finally, we conducted cell experiments to investigate the potential role of GPR143 in SKCM. RESULTS: We demonstrated a significantly high expression level of GPR143 in SKCM compared with normal tissues. High GPR143 expression and hypomethylation status of GPR143 were associated with a poorer prognosis. ROC analysis showed that the diagnostic efficacy of the GPR143 was 0.900. Furthermore, GPR143 expression was significantly correlated with immune infiltration in SKCM. We identified 20 neighbor genes and the pathways they enriched were anabolic process of pigmentation, immune regulation, and so on. Genomic alteration analysis revealed significantly different copy number variations related to GPR143 expression in SKCM, and shallow deletion could lead to high expression of GPR143. Ten potential therapeutic drugs against SKCM were identified. GPR143 knockdown inhibited melanoma cell proliferation, migration, and colony formation while promoting apoptosis. CONCLUSIONS: Our findings suggest that GPR143 serves as a novel diagnostic and prognostic biomarker and is associated with the progression of SKCM.

Relative Role of Age Groups and Indoor Environments in Influenza Transmission Under Different Urbanization Rates in China.

Exploring the relative role of different indoor environments in respiratory infections transmission remains unclear, which is crucial for developing targeted nonpharmaceutical interventions. In this study, a total of 2,583,441 influenza-like illness cases tested from 2010 to 2017 in China were identified. An agent-based model was built and calibrated with the surveillance data, to assess the roles of 3 age groups (children <19 years, younger adults 19-60 years, older adults >60 years) and 4 types of indoor environments (home, schools, workplaces, and community areas) in influenza transmission by province with varying urbanization rates. When the urbanization rates increased from 35% to 90%, the proportion of children aged <19 years among influenza cases decreased from 76% to 45%. Additionally, we estimated that infections originating from children decreased from 95.1% (95% confidence interval (CI): 92.7, 97.5) to 59.3% (95% CI: 49.8, 68.7). Influenza transmission in schools decreased from 80.4% (95% CI: 76.5, 84.3) to 36.6% (95% CI: 20.6, 52.5), while transmission in the community increased from 2.4% (95% CI: 1.9, 2.8) to 45.4% (95% CI: 35.9, 54.8). With increasing urbanization rates, community areas and younger adults contributed more to infection transmission. These findings could help the development of targeted public health policies. This article is part of a Special Collection on Environmental Epidemiology. This article is part of a Special Collection on Environmental Epidemiology.

Mixed Reality Combined with Surgical Navigation in Resection of Micro- and Mini-Tumors of the Parotid Gland: A Pilot Study.

OBJECTIVE: This study aimed to evaluate the feasibility and outcomes of mixed reality combined with surgical navigation (MRSN) in the resection of parotid micro- and mini-tumors. METHODS: Eighteen patients who underwent parotid tumor resection between December 2020 and November 2022 were included. Six patients were enrolled in MRSN group, and the surgeons performed the surgery with the help of MRSN technology. The surgical procedures include virtual planning, data transfer between mixed reality and surgical navigation, tumor localization and resection assisted by surgical navigation under mixed reality environment. Twelve patients were enrolled in control group, and intraoperative tumor localization and resection were performed according to the experience of the surgeon. Total surgery time and intraoperative bleeding were recorded. Perioperative complications were recorded during follow-up. RESULTS: The mean surgery time of MRSN group (76.7 ± 14.0 min) and control group (65.4 ± 21.3 min) showed no significant difference (p = 0.220), so did the intraoperative bleeding of MRSN group (16.0 ± 8.0 mL) and control group (16.7 ± 6.6 mL) (p = 0.825). None of the patient in MRSN group underwent any complication, although one patient in control group suffered temporary facial paralysis. The mean deviation between the virtually marked and the intraoperative actual outermost point of tumor was 3.03 ± 0.83 mm. CONCLUSION: MRSN technology can realize real-time three-dimensional visualization of the tumor, and it has the potential of enhancing the safety and accuracy of resection of micro- and mini-tumors of parotid gland. LEVEL OF EVIDENCE: 4 Laryngoscope, 134:1670-1678, 2024.

Highly active antiretroviral therapy-related effects on morphological connectivity in HIV.

OBJECTIVE: Suboptimal concentration of the antiretroviral drug is insufficient to inhibit HIV destruction on brain structure and function due to the resistance of blood brain barrier. We aimed to investigate highly active antiretroviral therapy (HAART)-related effects on the morphological connectivity in people with HIV (PWH). DESIGN: Case-control study. METHODS: Fifty-five HAART-treated for more than 3 months and 54 untreated PWH, as well as 66 demographically matched healthy controls underwent a high-resolution 3D T1-weighted MRI. Individual-level morphological brain network based on gray matter volume of 90 brain regions was constructed and network topological properties were analyzed. Network-based statistics (NBS) was performed to identify sub-networks showing significant differences in morphological connectivity. Correlation and mediation analyses were employed to evaluate associations between the morphological properties and clinical variables of PWH. RESULTS: Although PWH exhibited small-world architecture in their morphological brain networks, untreated PWH demonstrated altered network properties while HAART-treated PWH showed relatively similar network properties compared to healthy controls. Furthermore, HAART-related effects were mainly involved the bilateral putamen and left thalamus. The findings of NBS further indicated the cortico-striatum-thalamic-cortical loop was involved in the therapeutic-associated morphological network. The positive correlations between the HAART treatment and nodal degree and efficiency of the putamen were mediated by the number of CD4 + T lymphocytes. CONCLUSIONS: The topological properties are recovered to normal in PWH after HAART and the effects induced by HAART are mostly within the cortical-subcortical circuit.

Chemical constitutes from Tuber indicum with immunosuppressive activity uncovered by transcriptome analysis.

Three previously undescribed compounds including a polyketide (1) and two lactams (2 and 3) were obtained from Tuber indicum. The structures of new findings were elucidated by HRESIMS, NMR as well as NMR and ECD calculations. Transcriptome analysis through RNA-seq revealed that compound 2 exhibits immunosuppressive activity. Lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages were employed as a model to explore the effect of these compounds in immunosuppressive activity. The results showed that 2 could reduce the generation of inflammatory mediators including nitric oxide (NO), reactive oxygen species (ROS), interleukin 6 (IL-6), tumor necrosis factor α (TNF-α), cyclooxygenase 2 (COX-2) and inducible nitric oxide synthase (iNOS). Western blotting analysis demonstrated that 2 could suppressed the PI3K pathway by decreasing the levels of p-PI3K and p-Akt, while increasing the levels of p-PTEN. The anti-inflammatory activity of 2 was further confirmed using a zebrafish in vivo model.

A General Global and Local Pre-Training Framework for 3D Medical Image Segmentation.

Accurate target segmentation from computed tomography (CT) scans is crucial for surgical robots to perform clinical surgeries successfully. However, the lack of medical image data and annotations has been the biggest obstacle to learning robust medical image segmentation models. Self-supervised learning can effectively address this problem by providing a strategy to pre-train a model with unlabeled data, and then fine-tune downstream tasks with limited labeled data. Existing self-supervised methods fail to simultaneously utilize the abundant global anatomical structure information and local feature differences in medical imaging. In this work, we propose a new strategy for the pre-training framework, which uses the three-dimensional anatomical structure of medical images and specific task and background cues to segment volumetric medical images with limited annotations. Specifically, we propose (1) learning intrinsic patterns of volumetric medical image structures through multiple sub-tasks, and (2) designing a multi-level background cube contrastive learning strategy to enhance the target feature representation by exploiting the differences between the specific target and background. We conduct extensive evaluations on two publicly available datasets. Under limited annotation settings, the proposed method yields significant improvements compared to other self-supervised learning techniques. The proposed method achieves within 6% of the baseline performance using only five labeled CT volumes for training. Once the paper is online, the code and dataset will be available at https://github.com/PinkGhost0812/SGL.

In Situ Pt Migration Enabled Resurrection of Electrocatalyst and Fuel Cell Device.

In direct methanol fuel cells (DMFCs), the poisoning of noble metals is considered to be a major impediment to their commercial development. Here, it is found that the loss of surface Pt is one main reason for the attenuation of catalyst performance during long-time methanol oxidation reaction (MOR). A strategy to realize in situ resurrection of the deactivated catalyst by migrating Pt atoms inside to the surface is innovatively proposed. A high-activity Pt-SnO2 is designed, whose MOR activity is resurrected to 97.4% of the initial value. Based on this, the multiple resurrection of a DMFC device is also achieved for the first time. This work provides a new approach for the solution of catalyst deactivation and the development of sustainable catalysts as well as fuel cells.

Biomechanical behavior of the three-dimensionally printed surgical plates for mandibular defect reconstruction: a finite element analysis.

The aim of the study was to investigate the biomechanical behavior of three-dimensionally (3D)-printed surgical plates used for mandibular defect reconstruction, compare them with conventional surgical plates, and provide experimental evidence for their clinical application. Three-dimensional models were created for the normal mandible and for mandibular body defects reconstructed using free fibula and deep circumflex iliac artery flaps. Three-dimensional finite element models of reconstructed mandibles fixed using 3D-printed and conventional surgical plates were established. Vertical occlusal forces were applied to the remaining teeth and the displacement and Von Mises stress distributions were studied using finite element analysis. The normal and reconstructed mandibles had similar biomechanical behaviors. The displacement distributions for the surgical plates were similar, and the maximum total deformation occurred at the screw hole of the anterior segment of the surgical plates. However, there were differences in the Von Mises stress distributions for the surgical plates. In reconstructed mandibles fixed using 3D-printed surgical plates, the maximum equivalent Von Mises stress occurred at the screw hole of the posterior segment, while in those fixed using conventional surgical plates, the maximum equivalent Von Mises stress was at the screw hole of the anterior segment. In the mandible models reconstructed with the same free flap but fixed with different surgical plates, the plates had similar biomechanical behaviors. The biomechanical behavior of 3D-printed surgical plates was similar to conventional surgical plates, suggesting that 3D-printed surgical plates used to reconstruct mandibular body defects with vascularized autogenous bone grafts could lead to secure and stable fixation.

The causal relationship between pure hypercholesterolemia and psoriasis: A bidirectional, two-sample Mendelian randomization study.

BACKGROUND: Several studies have reported the association between pure hypercholesterolemia (PH) and psoriasis, but the causal effect remains unclear. METHODS: We explored the causal effect between PH and psoriasis using two-sample bidirectional Mendelian randomization (MR) analysis using data from genome-wide association studies. Single nucleotide polymorphisms related with exposures at the genome-wide significance level (p < 5×10-8 ) and less than the linkage disequilibrium level (r2  < 0.001) were chosen as instrumental variables. Subsequently, we used inverse variance weighting (IVW), MR-Egger and weighted median (WM) methods for causal inference. p < 0.05 was considered statistically significant. Heterogeneity was tested using Cochran's Q-test, and horizontal pleiotropy was examined using the MR-Egger intercept. Leave-one-out analyses were performed to assess the robustness and reliability of the results. RESULTS: MR results showed a positive causal effect of PH on psoriasis [IVW: odds ratios (OR): 1.139, p = 0.032; MR-Egger: OR: 1.434, p = 0.035; WM: OR: 1.170, p = 0.045] and psoriatic arthritis (PsA) (IVW: OR: 1.210, p = 0.049; MR-Egger regression: OR: 1.796, p = 0.033; WM: OR: 1.317, p = 0.028). However, there is no causal relationship between PH and psoriasis vulgaris as well as other unspecified psoriasis. Inverse MR results suggested a negative causal relationship between PsA and PH (IVW: OR: 0.950, p = 0.037). No heterogeneity and horizontal pleiotropy exist, and these results were confirmed to be robust. CONCLUSION: PH has a positive casual effect on psoriasis and PsA, and PsA may reduce the risk of having PH.