Per- and polyfluoroalkyl substances and bone mineral content in early adolescence: Modification by diet and physical activity.

BACKGROUND: Per- and polyfluoroalkyl substance (PFAS) exposures may negatively impact bone mineral accrual, but little is known about potential mitigators of this relation. We assessed whether associations of PFAS and their mixture with bone mineral content (BMC) in adolescence were modified by diet and physical activity. METHODS: We included 197 adolescents enrolled in a prospective pregnancy and birth cohort in Cincinnati, Ohio (2003-2006). At age 12 years, we collected serum for PFAS measurements and used dual-energy x-ray absorptiometry to measure BMC. We calculated dietary calcium intake and Health Eating Index (HEI) scores from repeated 24-h dietary recalls, physical activity scores using the Physical Activity Questionnaire for Older Children (PAQ-C), and average moderate to vigorous physical activity (MVPA) based on accelerometry. We estimated covariate-adjusted differences in BMC z-scores per interquartile range (IQR) increase of individual PFAS concentrations using linear regression and per simultaneous IQR increase in all four PFAS using g-computation. We evaluated effect measure modification (EMM) using interaction terms between each modifier and PFAS. RESULTS: Higher serum perfluorooctanoic acid, perfluorooctanesulfonic acid, and perfluorononanoic acid concentrations and the PFAS mixture were associated with lower BMC z-scores. An IQR increase in all PFAS was associated with a 0.27 (-0.54, 0.01) lower distal radius BMC z-score. Associations with lower BMC were generally stronger among adolescents classified as < median for calcium intake, HEI scores, or MVPA compared to those ≥ median. The difference in distal radius BMC z-score per IQR increase in all PFAS was -0.38 (-0.72, -0.04) for those with

Development of a disease-based hospital-level diagnostic intensity index.

OBJECTIVES: Low-value care is associated with increased healthcare costs and direct harm to patients. We sought to develop and validate a simple diagnostic intensity index (DII) to quantify hospital-level diagnostic intensity, defined by the prevalence of advanced imaging among patients with selected clinical diagnoses that may not require imaging, and to describe hospital characteristics associated with high diagnostic intensity. METHODS: We utilized State Inpatient Database data for inpatient hospitalizations with one or more pre-defined discharge diagnoses at acute care hospitals. We measured receipt of advanced imaging for an associated diagnosis. Candidate metrics were defined by the proportion of inpatients at a hospital with a given diagnosis who underwent associated imaging. Candidate metrics exhibiting temporal stability and internal consistency were included in the final DII. Hospitals were stratified according to the DII, and the relationship between hospital characteristics and DII score was described. Multilevel regression was used to externally validate the index using pre-specified Medicare county-level cost measures, a Dartmouth Atlas measure, and a previously developed hospital-level utilization index. RESULTS: This novel DII, comprised of eight metrics, correlated in a dose-dependent fashion with four of these five measures. The strongest relationship was with imaging costs (odds ratio of 3.41 of being in a higher DII tertile when comparing tertiles three and one of imaging costs (95 % CI 2.02-5.75)). CONCLUSIONS: A small set of medical conditions and related imaging can be used to draw meaningful inferences more broadly on hospital diagnostic intensity. This could be used to better understand hospital characteristics associated with low-value care.

Role of Helicobacter pylori virulence factors and alteration of the Tumor Immune Microenvironment: challenges and opportunities for Cancer Immunotherapy.

Various forms of malignancies have been linked to Helicobacter pylori. Despite advancements in chemotherapeutic and surgical approaches, the management of cancer, particularly at advanced stages, increasingly relies on the integration of immunotherapy. As a novel, safe therapeutic modality, immunotherapy harnesses the immune system of the patient to treat cancer, thereby broadening treatment options. However, there is evidence that H. pylori infection may influence the effectiveness of immunotherapy in various types of cancer. This association is related to H. pylori virulence factors and the tumor microenvironment. This review discusses the influence of H. pylori infection on immunotherapy in non-gastrointestinal and gastrointestinal tumors, the mechanisms underlying this relationship, and directions for the development of improved immunotherapy strategies.

Multifunctional chitosan-based gel sponge with efficient antibacterial, hemostasis and strong adhesion.

Developing wound dressings with solid adhesive properties that enable efficient, painless hemostasis and prevent wound infection remain a huge challenge. Herein, the tris(hydroxymethyl) methyl glycine-modified chitosan derivative (CTMG) was prepared and freeze-dried after simply adjusting the concentration of CTMG to obtain the chitosan-based gel sponge with desired multi-hollow structure, special antibacterial and biocompatibility. The adhesion strength on porcine skin was impressive up to 113 KPa, much higher than fibrin glue. It can withstand the pressure that far exceeds blood pressure. CTMG exhibits bacteriostatic abilities as demonstrated in a bacteriostatic assay, and alongside biocompatibility, as shown in cytotoxicity and hemolytic assays. Moreover, CTMG gel sponge showed hemostatic properties in both in vivo and in vitro hemostasis experiments. During an experiment on liver hemorrhage in rats, CTMG gel sponge proved to be more effective in controlling bleeding than other hemostatic sponges available on the market, indicating its promising hemostatic properties. CTMG gel sponge possesses the potential to function as a wound dressing and hemostatic material, making it suitable for various clinical applications.

Emergency Department Length of Stay for Older Adults With Dementia.

STUDY OBJECTIVE: The emergency department (ED) poses unique challenges and risks to persons living with dementia. A longer ED length of stay is associated with the risk of death, delirium, and medication errors. We sought to determine whether ED length of stay differed by dementia status and trends in ED length of stay for persons living with dementia from 2014 to 2018 and whether persons living with dementia were at a higher risk for prolonged ED length of stay (defined as a length of stay > 90th percentile). METHODS: In this observational study, we used data from the Healthcare Cost and Utilization Project State Emergency Department Database from Massachusetts, Arkansas, Arizona, and Florida. We included ED visits resulting in discharge for adults aged ≥65 years from 2014 to 2018. We used inverse probability weighting to create comparable groups of visits on the basis of dementia status. We used generalized linear models to estimate the mean difference in ED length of stay on the basis of dementia status and logistic regression to determine the odds of prolonged ED length of stay. RESULTS: We included 1,039,497 ED visits (mean age: 83.5 years; 64% women; 78% White, 12% Hispanic). Compared with visits by persons without dementia, ED length of stay was 3.1 hours longer (95% confidence interval [CI] 3.0 to 3.3 hours) for persons living with dementia. Among the visits resulting in transfer, ED length of stay was on average 4.1 hours longer (95% CI 3.6 to 4.5 hours) for persons living with dementia. Visits by persons living with dementia were more likely to have a prolonged length of stay (risk difference 4.1%, 95% CI 3.9 to 4.4). CONCLUSION: ED visits were more than 3 hours longer for persons living with versus without dementia. Initiatives focused on optimizing ED care for persons living with dementia are needed.

Treatment of hypertrophic scars with ablative fractional carbon dioxide laser assisted with different topical triamcinolone delivery ways.

Objectives: Ablative fractional carbon dioxide laser has been used with triamcinolone to treat hypertrophic scars, resulting in promising success rates. However, there are different topical triamcinolone delivery methods used in scar treatment. To assess the efficacy among the different triamcinolone delivery methods, this study was designed to compare the efficacy and safety of ablative fractional carbon dioxide laser followed by penetration and injection of topical triamcinolone into thicker hypertrophic scars (height score of VSS ≥2). Study design/materials and methods: We performed a retrospective study of 155 thicker hypertrophic scar patients (height score of VSS ≥2), including 88 patients in the triamcinolone external application group and 67 patients in the triamcinolone intralesional injection group. One month after the patients had 3 treatment sessions at 4-week intervals, the scars were assessed by photography, the Vancouver Scar Scale (VSS), durometry and spectrocolorimetry. Any adverse effects were also evaluated. Results: The VSS scores and the hardness of the scars in both groups improved significantly compared to baseline. Moreover, the patients in the triamcinolone intralesional injection group had higher treatment efficacy (19.77 ± 21.25 %) based on their VSS scores than the patients in the triamcinolone external application group (5.94 ± 24.07 %), especially in the improvement of scar pliability, height and hardness. Meanwhile, in the triamcinolone injection group, more patients had mild and moderate improvement than in the triamcinolone application group. However, there were no differences in the distribution of the adverse effects in either group. Conclusions: This study demonstrated that using the ablative fractional carbon dioxide laser followed by different topical triamcinolone delivery methods is effective and safe for thicker hypertrophic scar improvement. The method of using the ablative fractional carbon dioxide laser assisted with triamcinolone injection had a better therapeutic outcome in thicker hypertrophic scars, as compared with triamcinolone penetration.

Exploration of the Linkages between Lignin and Carbohydrates in Kraft Pulp from Wheat Straw Using a 13C/2H Isotopic Tracer.

To further our understanding of the change in association between lignin and carbohydrates after kraft pulping, isotope-labeled kraft pulp (KP) was prepared using 13C and D double-isotope-labeled wheat straw, and it was subjected to enzymatic hydrolysis and ionic liquid treatment to explore the linkages between lignin and carbohydrate complexes in wheat straw. Isotope abundance determination showed that 13C and D abundances in the experimental groups were substantially higher than those in the control group, indicating that the injected exogenous coniferin-[α-13C], coniferin-[γ-13C], and d-glucose-[6-D2] were effectively absorbed and metabolized during wheat internode growth. Solid-state CP/MAS 13C-NMR spectroscopy showed that lignin was mainly linked to polysaccharides via acetal, benzyl ether, and benzyl ester bonds. Kraft pulp (KP) from the labeled wheat straw was degraded by cellulase. The obtained residue was fractionated using the ionic liquid DMSO/TBAH to separate the cellulose-lignin complex (KP-CLC) and xylan-lignin complex (KP-XLC). X-ray diffractometer determination showed that the KP-CLC regenerated cellulose type II from type I after the ionic liquid conversion. The 13C-NMR spectrum of Ac-En-KP-CLC showed that the cellulose-lignin complex structure was chemically bonded between the lignin and cellulose through acetal and benzyl ether bonds. The 13C-NMR spectrum of En-KP-XLC showed a lignin-hemicellulose complex structure, wherein lignin and xylan were chemically bonded by benzyl ether and acetal bonds. These results indicate that the cross-linking between lignin and carbohydrates exists in lignocellulosic fibers even after kraft pulping.

Indocyanine Green Fluorescence Imaging in the Surgical Management of Skin Squamous Cell Carcinoma.

Introduction: Indocyanine green (ICG) fluorescence imaging has been used in the resection surgery and sentinel lymph node biopsy of many tumors. The aim of the present study is to verify the feasibility and effectiveness of ICG fluorescence imaging used for guiding the biopsy and resection of skin squamous cell carcinoma (SSCC). Methods: Sixty patients were enrolled, including 18 patients of suspected SSCC and 42 patients of diagnosed SSCC on admission. The ICG fluorescence imaging-guided skin biopsy was performed preoperatively in the 18 cases of suspected SSCC. Fifty-three patients underwent ICG fluorescence imaging-guided radical excision. Results: The results showed that 138 skin tissue samples in 60 patients with preoperative or intraoperative ICG fluorescence imaging-guide biopsy were collected. For a total number of 138 biopsies, 122 specimens were squamous cell carcinoma, and the accuracy rate was 88.4%, which was significantly higher than that of the group without preoperative ICG fluorescence imaging (41/62, 66.1%, P < 0.05). Fifty-three patients underwent surgery guided with ICG fluorescence imaging. Residual fluorescent signals in 24 patients were intraoperatively found and the excision was then expanded until the signals disappeared. Follow-up to November 2022, 12 patients died, of which 5 cases died from the tumor recurrence, and the others died due to advanced ages or other reasons. The recurrence rate was 9.4%, which was not significantly different from that of the group received routine radical resection (4/35, 11.4%, P > 0.05). Moreover, sentinel lymph nodes were successfully detected under ICG fluorescence imaging in the 4 patients with suspected lymph node metastases, and the location of lymph nodes can be precisely identified. Conclusion: ICG fluorescence imaging technique can guide the pathology biopsy to improve the accuracy of pathological examination, and help to identify the boundaries of tumor tissues and sentinel lymph nodes to resect tumor radically during operation.

clusterMLD: An Efficient Hierarchical Clustering Method for Multivariate Longitudinal Data.

Longitudinal data clustering is challenging because the grouping has to account for the similarity of individual trajectories in the presence of sparse and irregular times of observation. This paper puts forward a hierarchical agglomerative clustering method based on a dissimilarity metric that quantifies the cost of merging two distinct groups of curves, which are depicted by B-splines for the repeatedly measured data. Extensive simulations show that the proposed method has superior performance in determining the number of clusters, classifying individuals into the correct clusters, and in computational efficiency. Importantly, the method is not only suitable for clustering multivariate longitudinal data with sparse and irregular measurements but also for intensely measured functional data. Towards this end, we provide an R package for the implementation of such analyses. To illustrate the use of the proposed clustering method, two large clinical data sets from real-world clinical studies are analyzed.

Biotransformed bear bile powder ameliorates diet-induced nonalcoholic steatohepatitis in mice through modulating arginine biosynthesis via FXR/PXR-PI3K-AKT-NOS3 axis.

NASH is a highly prevalent metabolic syndrome that has no specific approved agents up to now. BBBP, which mainly contains bile acids, possess various pharmacological properties and some bile acids are available for NASH treatment. Herein, the therapeutic effects and underlying mechanisms of BBBP against NASH were systemically evaluated. In this study, mice received an HFHS diet over a 20-week period to induce NASH with or without BBBP intervention were used to evaluate the effect and underlying mechanisms of BBBP against NASH. Our results demonstrated that BBBP attenuated hepatic steatosis, reduced body weight gain and lipid concentrations, and improved sensitivity to insulin and tolerance to glucose in mice fed an HFHS diet. Metabolomics and transcriptomic analysis revealed that BBBP suppressed the arginine biosynthesis by up-regulating NOS3 expression and the PI3K-Akt signaling pathway was also regulated by BBBP, as indicated by 55 DEGs. Bioinformatic analysis predicted the regulatory effect of the FXR/PXR-PI3K-AKT-NOS3 axis on arginine biosynthesis-related metabolites. These results were further confirmed by the significantly increased mRNA and protein levels of NOS3, PI3K (Pik3r2), and AKT1. And the increased levels of arginine biosynthesis related-metabolites, such as urea, aspartic acid, glutamic acid, citrulline, arginine, and ornithine, were confirmed accurately based on targeted metabolomics analysis. Together, our study uncoded the complicated mechanisms of anti-NASH activities of BBBP, and provided critical evidence inspiring the discovery of innovative therapies based on BBBP in the treatment of NASH.

Clustering-Evolved Frontier Orbital for Low-Temperature CO2 Dissociation.

In this study, single Ni2 clusters (two Ni atoms bridged by a lattice oxygen) are successfully synthesized on monolayered CuO. They exhibit a remarkable activity toward low-temperature CO2 thermal dissociation, in contrast to cationic Ni atoms that nondissociatively adsorb CO2 and metallic Ni ones that are chemically inert for CO2 adsorption. Density functional theory calculations reveal that the Ni2 clusters can significantly alter the spatial symmetry of their unoccupied frontier orbitals to match the occupied counterpart of the CO2 molecule and enable its low-temperature dissociation. This study may help advance single-cluster catalysis and exploit the unexcavated mechanism for low-temperature CO2 activation.

PubPredict: Prediction of progression and survival in oncology leveraging publications and early efficacy data.

In oncology/hematology early phase clinical trials, efficacies were often observed in terms of response rate, depth, timing, and duration. However, the true clinical benefits that eventually support registrational purpose are progression-free survival (PFS) and/or overall survival (OS), the follow-up of which are typically not long enough in early phase trials. This gap imposes challenges in strategies for late phase drug development. In this article, we tackle the question by leveraging published study to establish a quantitative link between early efficacy outcomes and late phase efficacy endpoints. We used solid tumor cancer as disease model. We modeled the disease course of a RECISTv1.1 assessed solid tumor with a continuous Markov chain (CMC) model. We parameterize the transition intensity matrix of a CMC model based on published aggregate-level summary statistics, and then simulate subject-level time-to-event data. The simulated data is shown to have good approximation to published studies. PFS and/or OS could be predicted with the transition intensity matrix modified given clinical knowledge to reflect various assumptions on response rate, depth, timing, and duration. The authors have built a R shiny application named PubPredict, the tool implements the algorithm described above and allows customized features including multiple response levels, treatment crossover and varying follow-up duration. This toolset has been applied to advise phase 3 trial design when only early efficacy data are available from phase 1 or 2 studies.

[Effect of MELK Inhibitor OTSSP167 on Diffuse Large B-Cell Lymphoma].

OBJECTIVE: To investigate the effect of MELK inhibitor OTSSP167 against diffuse large B-cell lymphoma (DLBCL). METHODS: The effect of OTSSP167 on activity, proliferation, and apoptosis of DLBCL cell line (SUDHL2 and HBL1) was detected by CCK-8 assay, 5-ethynyl-2'-deoxyuridine (EdU) staining, and Annexin V-FITC/PI double staining, respectively. DLBCL cells were inoculated into nude mice, after 4 weeks of OTSSP167 treatment, the effect of OTSSP167 on DLBCL growth in vivo was detected. Caspase-GloTM 3/7 enzyme activity assay kit was used to detect the effect of OTSSP167 on Caspase 3/7 enzyme activity of DLBCL cells. The expression levels of apoptosis and cycle-related proteins were detected by Western blot. RESULTS: OTSSP167 significantly inhibited the activity of SUDHL2 and HBL1 cells in a dose-dependent manner (r =-0.61, r =-0.52). EdU staining showed that OTSSP167 could significantly inhibit the proliferation of SUDHL2 and HBL1 cells. Annexin V-FITC/PI result showed that OTSSP167 could significantly promote the apoptosis of SUDHL2 and HBL1 cells (P <0.001). The result of in vivo experiment showed that OTSSP167 could inhibit the growth of SUDHL2 cells in nude mice. The result of TUNEL staining of tumor further confirmed that OTSSP167 could promote the apoptosis of SUDHL2 cells. Caspase 3/7 enzyme activity test demonstrated that OTSSP167 could significantly increase caspase activity in SUDHL2 and HBL1 cells (r =0.98, r =0.87). Western blot showed that OTSSP167 could dose-dependently inhibit the expression of PARP, Bcl-xL, and Bcl-2 in apoptosis signaling pathway (r =-0.93, r =-0.66, r =-0.87), while p53 protein was significantly up-regulated (r =0.82). The expression of cell cycle-related proteins cdc2, Cyclin E1, Cyclin A2, and Cyclin B1 also showed a dose-dependent down-regulation (r =-0.89, r =-0.83, r =-0.61, r =-0.93). CONCLUSION: The MELK inhibitor OTSSP167 can inhibit the proliferation and promote the apoptosis of DLBCL cells by inhibiting the expression of cycle-related proteins and anti-apoptosis-related proteins.

Preparation and Anti-Lung Cancer Activity Analysis of Guaiacyl-Type Dehydrogenation Polymer.

In this paper, guaiacyl dehydrogenated lignin polymer (G-DHP) was synthesized using coniferin as a substrate in the presence of ß-glucosidase and laccase. Carbon-13 nuclear magnetic resonance (13C-NMR) determination revealed that the structure of G-DHP was relatively similar to that of ginkgo milled wood lignin (MWL), with both containing ß-O-4, ß-5, ß-1, ß-ß, and 5-5 substructures. G-DHP fractions with different molecular weights were obtained by classification with different polar solvents. The bioactivity assay indicated that the ether-soluble fraction (DC2) showed the strongest inhibition of A549 lung cancer cells, with an IC50 of 181.46 ± 28.01 µg/mL. The DC2 fraction was further purified using medium-pressure liquid chromatography. Anti-cancer analysis revealed that the D4 and D5 compounds from DC2 had better anti-tumor activity, with IC50 values of 61.54 ± 17.10 µg/mL and 28.61 ± 8.52 µg/mL, respectively. Heating electrospray ionization tandem mass spectrometry (HESI-MS) results showed that both the D4 and D5 were ß-5-linked dimers of coniferyl aldehyde, and the 13C-NMR and 1H-NMR analyses confirmed the structure of the D5. Together, these results indicate that the presence of an aldehyde group on the side chain of the phenylpropane unit of G-DHP enhances its anticancer activity.

Brief moderate-intensity aerobic exercise improves the executive function of Chinese undergraduates regardless of mobile phone addiction: Evidence from the antisaccade task.

Introduction: Previous studies have shown that brief moderate-intensity aerobic exercise can improve the executive function of healthy adults. The present study sought to examine and compare the effects of brief moderate-intensity aerobic exercise on the executive functions of undergraduates with and without mobile phone addiction. Method: Thirty-two healthy undergraduates with mobile phone addiction were recruited and randomly assigned to either an exercise or control group. Likewise, 32 healthy undergraduates without mobile phone addiction were recruited and randomly assigned to either an exercise or control group. Participants were asked to perform moderate-intensity aerobic exercise for 15 minutes for the exercise groups. The executive functions of all participants were assessed via the antisaccade task twice (i.e., pre-test and post-test). Results: The results showed that the saccade latency, variability of saccade latency, and error rate decreased significantly from pre-test to post-test for all participants. More importantly, after the 15-min moderate-intensity aerobic exercise intervention, participants in the exercise groups showed significantly shorter saccade latency than their counterparts in the control groups, regardless of whether they are with mobile phone addiction. Discussion: This result is consistent with previous studies demonstrating that brief moderate-intensity aerobic exercise can improve one's executive function. Furthermore, the absence of significant interaction among Time, Group, and Intervention implies that the effects of brief moderate-intensity aerobic exercise on executive function are comparable between participants with and without mobile phone addiction. The present study supports the previous conclusion that brief moderate-intensity aerobic exercise can improve one's executive function effectively, and extends it to the population with mobile phone addiction. In summary, the present study has some implications for understanding of the relationship between exercise, executive function, and mobile phone addiction.

Exploration of the shared pathways and common biomarker PAN3 in ankylosing spondylitis and ulcerative colitis using integrated bioinformatics analysis.

Background: Ulcerative colitis (UC) is a chronic autoimmune-related disease that causes inflammation of the intestine. Ankylosing spondylitis (AS) is a common extraintestinal complication of UC involving the sacroiliac joint. However, the pathogenesis of AS secondary to UC has not been studied. This study aimed to investigate the shared pathways and potential common biomarkers of UC and AS. Methods: Microarray data downloaded from the Gene Expression Omnibus (GEO) database were used to screen differentially expressed genes (DEGs) in the UC and AS datasets. Weighted gene co-expression network analysis (WGCNA) was performed to identify co-expression modules related to UC and AS. Shared genes were then further analyzed for functional pathway enrichment. Next, the optimal common biomarker was selected using SVM-RFF and further validated using two independent GEO datasets. Finally, immune infiltration analysis was used to investigate the correlation of immune cell infiltration with common biomarkers in UC and AS. Results: A total of 4428 and 2438 DEGs in UC and AS, respectively, were screened. Four modules were identified as significant for UC and AS using WGCNA. A total of 25 genes overlapped with the strongest positive and negative modules of UC and AS. KEGG analysis showed these genes may be involved in the mitogen-activated protein kinase (MAPK) signaling pathway. GO analysis indicated that these genes were significantly enriched for RNA localization. PAN3 was selected as the optimal common biomarker for UC and AS. Immune infiltration analysis showed that the expression of PAN3 was correlated with changes in immune cells. Conclusion: This study first explored the common pathways and genetic diagnostic markers involved in UC and AS using bioinformatic analysis. Results suggest that the MAPK signaling pathway may be associated with both pathogeneses and that PAN3 may be a potential diagnostic marker for patients with UC complicated by AS.

Physically active undergraduates perform better on executive-related oculomotor control: Evidence from the antisaccade task and pupillometry.

Previous studies have shown that exercise can improve executive function in young and older adults. However, it remains controversial whether a sufficient amount of physical activity leads to higher-level executive function. To examine the effect of physical activity on executive function, we used eye-tracking technology and the antisaccade task in 41 young undergraduates with various levels of physical activity. Moreover, we also investigated their differences in cognitive ability by examining their pupil size during the antisaccade task. Eye-tracking results showed that physically active individuals showed shorter saccade latency and higher accuracy in the antisaccade task than their physically inactive counterparts. Furthermore, the former showed larger pupil size during the preparatory period of antisaccade. These findings suggest that individuals with higher-level physical activity have higher-level executive function. The larger pupil sizes of physically active individuals may imply that their locus coeruleus-norepinephrine system and executive-related prefrontal cortex are more active, which contributes to their higher-level cognitive ability.

P311 Promotes IL-4 Receptor‒Mediated M2 Polarization of Macrophages to Enhance Angiogenesis for Efficient Skin Wound Healing.

The transition from the proinflammatory phase to the prohealing phase in wound healing is essential for effective skin wound repair, which involves the balance of M1 and M2 polarization of wound-infiltrating macrophages. P311 plays an essential role in promoting wound closure by enhancing the biological function of epidermal stem cells, endothelial cells, and fibroblasts. Nevertheless, whether and how P311 regulates macrophage polarization remains unclear. In this study, we showed that P311 deficiency reduced the M2 polarization of macrophages, thereby attenuating the secretion of M2-like cytokines. The P311 deficiency prolonged the transition from the proinflammatory phase to the prohealing phase, accompanied by weakened angiogenesis and retarded granulation tissue formation, both of which coordinately hinder the healing of skin wounds. Mechanistically, P311 deficiency downregulated the expression of IL-4 receptor on macrophages, followed by less activation of the IL-4 receptor‒signal transducer and activator of transcription 6 signaling pathway, resulting in impaired M2 macrophage polarization. We further revealed that the mTOR signaling pathway was associated with the regulation of P311 on the expression of IL-4 receptor in macrophages. Thus, our study has highlighted the pivotal role of P311 in promoting the M2 polarization of macrophages for effective skin wound healing.