Identification of miRNA expression profile in middle ear cholesteatoma using small RNA-sequencing.

BACKGROUND: The present study aims to identify the differential miRNA expression profile in middle ear cholesteatoma and explore their potential roles in its pathogenesis. METHODS: Cholesteatoma and matched normal retroauricular skin tissue samples were collected from patients diagnosed with acquired middle ear cholesteatoma. The miRNA expression profiling was performed using small RNA sequencing, which further validated by quantitative real-time PCR (qRT-PCR). Target genes of differentially expressed miRNAs in cholesteatoma were predicted. The interaction network of 5 most significantly differentially expressed miRNAs was visualized using Cytoscape. Further Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genome (KEGG) pathway enrichment analyses were processed to investigate the biological functions of miRNAs in cholesteatoma. RESULTS: The miRNA expression profile revealed 121 significantly differentially expressed miRNAs in cholesteatoma compared to normal skin tissues, with 56 upregulated and 65 downregulated. GO and KEGG pathway enrichment analyses suggested their significant roles in the pathogenesis of cholesteatoma. The interaction network of the the 2 most upregulated (hsa-miR-21-5p and hsa-miR-142-5p) and 3 most downregulated (hsa-miR-508-3p, hsa-miR-509-3p and hsa-miR-211-5p) miRNAs identified TGFBR2, MBNL1, and NFAT5 as potential key target genes in middle ear cholesteatoma. CONCLUSIONS: This study provides a comprehensive miRNA expression profile in middle ear cholesteatoma, which may aid in identifying therapeutic targets for its management.

LAYN Serves as a Prognostic Biomarker and Downregulates Tumor-Infiltrating CD8+ T Cell Function in Hepatocellular Carcinoma.

Background: Layilin (LAYN) represents a valuable prognostic biomarker across various tumor types, while also serving as an innovative indicator of dysfunctional or exhausted CD8+ T cells and exhibiting correlation with immune context. However, the immune function and prognostic significance of LAYN in hepatocellular carcinoma (HCC) remain unexplored. Therefore, our objective is to investigate the role of LAYN in CD8+ T cell exhaustion, clinical prognosis, and the tumor microenvironment within HCC. Methods: TIMER or GEPIA databases were used to analyze LAYN expression level and its correlation with immune infiltration in HCC. Bioinformatics analysis was conducted on TCGA and scRNA-seq cohorts. The evaluation of LAYN expression level in fresh specimens was performed through IF, IHC, and ELISA assays. Flow cytometry and mRNA-seq were employed to investigate co-expressed genes of LAYN, the LAYN+CD8+ T cell exhaustion signature and immune function. Cell proliferation ability and killing activity were assessed using CCK8 and CFSE/PI. Results: The expression level of LAYN in HCC tumors was significantly higher compared to peri-tumors. Patients with high levels of LAYN exhibited poorer OS. GO or KEGG analysis confirmed that LAYN was involved in immune response and was positively associated with CD8+ T cell immune infiltration levels. Furthermore, LAYN negatively regulated the immune function of CD8+ T cells, leading to dysfunctional phenotypes characterized by elevated levels of CD39, TIM3 and reduced levels of perforin, TNF-α, Ki-67. CFSE/PI assays demonstrated that LAYN+CD8+ T cells displayed decreased cytotoxic activity. Additionally, there was a positive correlation between LAYN and CD146 levels, which are involved in adhesion and localization processes of CD8+ T cells. Interestingly, blocking LAYN partially restored the exhaustion properties of CD8+ T cells. Conclusion: LAYN exhibits a strong correlation with immune infiltration in the TME and represents a novel biomarker for predicting clinical prognosis in HCC. Moreover, targeting LAYN may hold promise as an effective strategy for HCC immunotherapy.

Association between the atherogenic index of plasma and hearing loss based on a nationwide cross-sectional study.

BACKGROUND: Hearing loss (HL) is a worldwide public health issue for which the role of dyslipidemia has not been fully elucidated. This study aimed to use the atherogenic index of plasma (AIP), a well-established serum lipid marker, to investigate the association of dyslipidemia with HL among the general population. METHODS: Participants (n = 3267) from the National Health and Nutrition Examination Survey database (2005-2012, 2015-2018) were included in the present study. The AIP was calculated based on the following formula: log10 (triglycerides/high-density lipoprotein cholesterol). HL was defined as a pure-tone average of at least 20 dBHL in the better ear. Weighted multivariable logistic regression, subgroup analysis, generalized additive model, and threshold analysis were adopted to reveal the association between the AIP and HL. RESULTS: In this study of US adults, a positive association was found between the AIP and high-frequency HL. However, the association between the AIP and low-frequency HL was not as strong. In addition, a reverse L-shaped curve with an inflection point located at -0.27 was detected between the AIP and high-frequency HL, followed by a significant positive association after the inflection point. CONCLUSIONS: The potential of the AIP as a bioindicator for high-frequency HL is noteworthy, and maintaining an AIP value below a certain threshold might provide beneficial outcomes in the management of high-frequency HL.

Tumor-associated macrophage-induced circMRCKα encodes a peptide to promote glycolysis and progression in hepatocellular carcinoma.

The tumor-associated macrophages (TAMs) play multifaceted roles in the progression of hepatocellular carcinoma (HCC). However, the involvement of circular RNAs in the interplay between TAMs and HCC remains unclear. Based on Transwell co-culturing and circular RNA sequencing, this study revealed that TAMs enhanced tumor glycolysis and progression by upregulating circMRCKα in HCC cells. Patients with HCC who exhibited elevated circMRCKα levels presented significantly reduced overall survival and greater cumulative recurrence. Notably, we identified a novel functional peptide of 227 amino acids named circMRCKα-227aa, encoded by circMRCKα. Mechanistically, circMRCKα-227aa bound to USP22 and enhanced its protein level to obstruct HIF-1α degradation via the ubiquitin-proteasome pathway, thereby augmenting HCC glycolysis and progression. In clinical HCC samples, a positive correlation was observed between the expression of circMRCKα and the number of infiltrating CD68+ TAMs and expression of USP22. Furthermore, circMRCKα emerged as an independent prognostic risk factor both individually and in conjunction with CD68+ TAMs and USP22. This study illustrated that circMRCKα-227aa, a novel TAM-induced peptide, promotes tumor glycolysis and progression via USP22 binding and HIF-1α upregulation, suggesting that circMRCKα and TAMs could be combined as therapeutic targets in HCC.

Neutrophil extracellular traps in central nervous system (CNS) diseases.

Excessive induction of inflammatory and immune responses is widely considered as one of vital factors contributing to the pathogenesis and progression of central nervous system (CNS) diseases. Neutrophils are well-studied members of inflammatory and immune cell family, contributing to the innate and adaptive immunity. Neutrophil-released neutrophil extracellular traps (NETs) play an important role in the regulation of various kinds of diseases, including CNS diseases. In this review, current knowledge on the biological features of NETs will be introduced. In addition, the role of NETs in several popular and well-studied CNS diseases including cerebral stroke, Alzheimer's disease, multiple sclerosis, amyotrophic lateral sclerosis (ALS), and neurological cancers will be described and discussed through the reviewing of previous related studies.

Recent Advances in the Preparation of Protein/peptide Microspheres by Solvent Evaporation Method.

Protein/peptide drugs are extensively used to treat various chronic and serious diseases. The short half-life in vivo of protein and peptide as therapeutics drug limit the realization of complete effects. Encapsulating drugs in microspheres can slow the speed of drug release and prolong the efficacy of drugs. The solvent evaporation method is widely used to prepare protein/peptide microspheres because of its facile operation and minimal equipment requirements. This method has several challenges in the lower encapsulation efficiency, fluctuant release profiles and the stabilization of protein/peptides, which researchers believe may be solved by adjusting the preparation parameter or formulation of microspheres. The article discusses the formulation parameters that govern the preparation of protein/peptide-loaded microspheres by the solvent evaporation method, which provides an overview of the current promising strategies for solvent evaporation for protein/peptide microspheres. The article takes parameter evaluation as the framework, facilitating subsequent researchers to quickly find possible solutions when encountering problems.

A retrospective cohort study to examine factors affecting live birth after hysteroscopic treatment of intrauterine adhesions.

OBJECTIVE: To evaluate independent factors that affect the chance of live birth (LB) after hysteroscopic adhesiolysis in patients with intrauterine adhesions. DESIGN: Retrospective cohort study. SETTING: Hysteroscopic center of Fuxing Hospital in Beijing, China. PATIENT(S): Patients diagnosed with Asherman syndrome between June 2020, and February 2022. INTERVENTION(S): Hysteroscopic adhesiolysis is followed by a second look hysteroscopy to assess the outcome and follow-up for a year. MAIN OUTCOME MEASURE(S): Live birth rate (LBR) without the use of assisted reproductive technologies at 12-month follow-up. RESULT(S): Of the 544 women included in the cohort, the pregnancy rate at the end of 1 year of follow-up was 47.6% (95% confidence interval [CI] 45.5%-49.7%), and the LBR was 41.0% (95% CI 38.9%-43.1%). Stepwise multiple logistic regression analysis identified three independent predictors of LB in decreasing order of significance: increase in menstrual flow after surgery (odds ratio [OR] 3.69, 95% CI 1.77-8.21), postoperative endometrial thickness in the midluteal phase (OR 1.53, 95% CI 1.31-1.80), and the severity of recurred adhesion at second-look hysteroscopy (OR 0.62, 95% CI 0.50-0.76). Among subjects with good independent prognostic factors, namely, increased menstrual flow after surgery, postoperative endometrial thickness in the midluteal phase >6 mm, and no or minimal recurrence of adhesions at second-look hysteroscopy, the LBR was 69.0% (95% CI 65.4%-72.6%). On the other hand, in women (n = 26) without any of the three good prognostic factors, none had a successful LB (0). CONCLUSION(S): Overall, the LBR after treatment for Asherman syndrome was 41.0%. The prognosis is dependent on three outcome measures after surgery, namely, improvement in menstrual flow, postoperative endometrial thickness, and the minimal degree of recurrent adhesions at second-look hysteroscopy.

Serial circulating tumor DNA profiling predicts tumor recurrence after liver transplantation for liver cancer.

BACKGROUND: Minimal residual disease (MRD) is proposed to be responsible for tumor recurrence. The role of circulating tumor DNA (ctDNA) to detect MRD, monitor recurrence, and predict prognosis in liver cancer patients undergoing liver transplantation (LT) remains unrevealed. METHODS: Serial blood samples were collected to profile ctDNA mutational changes. Baseline ctDNA mutational profiles were compared with those of matched tumor tissues. Correlations between ctDNA status and recurrence rate (RR) and recurrence-free survival (RFS) were analyzed, respectively. Dynamic change of ctDNA was monitored to predict tumor recurrence. RESULTS: Baseline mutational profiles of ctDNA were highly concordant with those of tumor tissues (median, 89.85%; range 46.2-100%) in the 74 patients. Before LT, positive ctDNA status was associated with higher RR (31.7% vs 11.5%; p = 0.001) and shorter RFS than negative ctDNA status (17.8 vs 19.4 months; p = 0.019). After LT, the percentage of ctDNA positivity decreased (17.6% vs 47.0%; p < 0.001) and patients with positive ctDNA status had higher RR (46.2% vs 21.3%; p < 0.001) and shorter RFS (17.2 vs 19.2 months; p = 0.010). Serial ctDNA profiling demonstrated patients with decreased or constant negative ctDNA status had lower RR (33.3% vs 50.0%; p = 0.015) and favorable RFS (18.2 vs 15.0 months, p = 0.003) than those with increased or constant positive ctDNA status. Serial ctDNA profiling predicted recurrence months ahead of imaging evidence and serum tumor biomarkers. CONCLUSIONS: ctDNA could effectively detect MRD and predict tumor recurrence in liver cancer patients undergone LT.

Guidelines for the Diagnosis and Treatment of Primary Liver Cancer (2022 Edition).

Background: Primary liver cancer, of which around 75-85% is hepatocellular carcinoma in China, is the fourth most common malignancy and the second leading cause of tumor-related death, thereby posing a significant threat to the life and health of the Chinese people. Summary: Since the publication of Guidelines for Diagnosis and Treatment of Primary Liver Cancer in China in June 2017, which were updated by the National Health Commission in December 2019, additional high-quality evidence has emerged from researchers worldwide regarding the diagnosis, staging, and treatment of liver cancer, that requires the guidelines to be updated again. The new edition (2022 Edition) was written by more than 100 experts in the field of liver cancer in China, which not only reflects the real-world situation in China but also may reshape the nationwide diagnosis and treatment of liver cancer. Key Messages: The new guideline aims to encourage the implementation of evidence-based practice and improve the national average 5-year survival rate for patients with liver cancer, as proposed in the "Health China 2030 Blueprint."

The use of intrauterine balloon therapy in reproductive medicine and surgery: a guidance for practice.

The use of balloon therapy in obstetric practice especially in postpartum haemorrhage (PPH) is well established and has recently been reviewed. However, little attention has been drawn regarding the use of intrauterine balloon (IUB) in gynaecological practice. This study focuses on the various usage of IUB in gynaecological practice. An electronic literature search through Medline, EMBASE and Clinicaltrial.gov from inception to August 2022 was conducted. The study focuses on the three following areas: (1) Indications: prevention and removal of intrauterine adhesions, management of ectopic pregnancy, facilitation of endoscopic surgery and other clinical usages; (2) Practical aspects of balloon therapy including ultrasound guidance, choice of balloon, inflation volume, duration of balloon therapy; and (3) Potential complications including pain, infection, uterine rupture and how they can be avoided. IUB therapy is a simple, inexpensive and effective method that can be applied in various gynaecological conditions ranging from IUA to intrauterine haemorrhage. Complications are rare, but in most cases can be avoided with correct use.

Does non-cavity distorting intramural fibroid affect endometrium around the time of embryo implantation?

The effect of the intramural fibroids not distorting the cavity remains controversial on implantation and pregnancy. The aim of this study was to examine the impact of non-cavity distorting intramural fibroids on endometrium. Fifty-six women with non-cavity distorting intramural fibroid were recruited in this study. Paired endometrial specimens, one from beneath the fibroid (ipsilateral endometrium) and the other from the opposite side of uterine cavity, away from the fibroid (contralateral endometrium) were obtained 7-9 days after the luteinizing hormone surge in a natural cycle. Histological dating, Mucin1 and Glycodelin expression and uterine natural killer (uNK) cell density were compared between the paired samples. The median (IQR) H-score of Mucin1 staining in the ipsilateral luminal epithelium was 210% (142-230%), which was significantly (p < 0.05) higher than that of the contralateral luminal endometrium (157%, IQR 114-176%). There was no significant difference in Mucin1 expression in the glandular epithelium. There was no significant difference in Glycodelin expression in luminal and glandular epithelium, uNK cells density or histological dating results between the paired endometrial samples. In conclusion, it is uncertain whether the altered expression of Mucin1 in luminal epithelium alone may have impact on implantation when other markers are not changed.

ZNT1 and Zn 2+ control TLR4 and PD-L1 endocytosis in macrophages to improve chemotherapy efficacy against liver tumor.

BACKGROUND AND AIMS: HCC is closely associated with inflammation and immune modulation, and combined chemotherapy with other strategies is under extensive investigation to achieve better efficacy. HCC is accompanied by zinc (Zn) deficiency. This study aims to understand how Zn could affect macrophage function and its application for HCC therapy. APPROACH AND RESULTS: Zn 2+ and the Zn transporter 1 (ZNT1, solute carrier family 30 member 1) were markedly reduced in intrahepatic macrophages from patients with HCC and from mouse liver tumors. Lower ZNT1 expression was associated with higher IL-6 production and shorter survival time in patients with HCC. Critically, ZNT1 regulated endosomal Zn 2+ levels for endocytosis of toll-like receptor 4 and programmed cell death ligand 1, thereby decreasing macrophage-induced inflammation and immunosuppression to protect from liver tumors. Myeloid-specific deletion of ZNT1 in mice increased chronic inflammation, liver fibrosis, tumor numbers, and size. Notably, Zn supplementation could reduce inflammation and surface programmed cell death ligand 1 expression in macrophages with the increased CD8 + T cell cytotoxicity, which synergized the antitumor efficacy of Sorafenib/Lenvatinib. CONCLUSIONS: Our study proposes a new concept that ZNT1 and Zn regulate endosome endocytosis to maintain surface receptors, and Zn supplements might be synergized with chemotherapy to treat inflammation-associated tumors, especially those containing programmed cell death ligand 1 + myeloid cells.

Testing and Analysis of Ultra-High Toughness Cementitious Composite-Confined Recycled Aggregate Concrete under Axial Compression Loading.

In order to analyze the axial compressive properties of ultra-high-toughness cementitious composite (UHTCC)-confined recycled aggregate concrete (RAC), a batch of UHTCC-confined RAC components was designed and manufactured according to the requirements of GB/T50081-2002 specifications. After analyzing the surface failure phenomenon, load-displacement curves, scanning electron microscope (SEM), and parameter analysis of the specimen, the result shows that UHTCC-confined RAC is an effective confinement method, which can effectively improve the mechanical properties and control the degree of surface failure of RAC structures. Compared with the unconfined specimen, the maximum peak load of the UHTCC confinement layer with a thickness of 10 mm and 20 mm increased by 44.61% and 79.27%, respectively, meeting the requirements of engineering practice. Different fiber mixing amounts have different effects on improving the mechanical performance of RAC structural. The specific rule was steel fiber (SF) > polyvinyl alcohol fiber (PVAF) > polyvinyl alcohol fiber (PEF) > no fiber mixture, and the SF improves the axial compression properties of UHTCC most significantly. When there are strict requirements for improving the mechanical properties of the structure, SF should be added to UHTCC. On the contrary, PVAF should be added to UHTCC.

Blockade of TGF-ß signalling alleviates human adipose stem cell senescence induced by native ECM in obesity visceral white adipose tissue.

BACKGROUND: Abdominal obesity is appreciated as a major player in insulin resistance and metabolically dysfunctional adipose tissue. Inappropriate extracellular matrix (ECM) remodelling and functional alterations in human adipose stromal/stem cells (hASCs) have been linked with visceral white adipose tissue (vWAT) dysfunction in obesity. Understanding the interactions between hASCs and the native ECM environment in obese vWAT is required for the development of future therapeutic approaches for obesity-associated metabolic complications. METHODS: The phenotypes and transcriptome properties of hASCs from the vWAT of obese patients and lean donors were assessed. The hASC-derived matrix from vWAT of obese or lean patients was generated in vitro using a decellularized method. The topography and the major components of the hASC-derived matrix were determined. The effects of the obese hASC-derived matrix on cell senescence and mitochondrial function were further determined. RESULTS: We showed that hASCs derived from the vWAT of obese patients exhibited senescence and were accompanied by the increased production of ECM. The matrix secreted by obese hASCs formed a fibrillar suprastructure with an abundance of fibronectin, type I collagen, and transforming growth factor beta 1 (TGF-ß1), which resembles the native matrix microenvironment of hASCs in vWAT derived from obese patients. Furthermore, the obese hASC-derived matrix promoted lean hASC ageing and induced mitochondrial dysfunction compared to the lean hASC-derived matrix. Blockade of TGF-ß1 signalling using an anti-TGF-ß1 neutralizing antibody alleviated the lean hASC senescence and mitochondrial dysfunction induced by the obese hASC-derived matrix. CONCLUSIONS: Native ECM in obesity vWAT initiates hASC senescence through TGF-ß1-mediated mitochondrial dysfunction. These data provide a key mechanism for understanding the importance of cell-ECM interactions in hASCs senescence in obesity.

Monitoring and Analysis of the Collapse Process in Blasting Demolition of Tall Reinforced Concrete Chimneys.

Aiming at the problem of displacement of collapse direction caused by the impact of the high-rise reinforced concrete chimney in the process of blasting demolition, combined with the monitoring methods such as high-speed photography observation, piezoelectric ceramic sensor, and blasting vibration monitor, the impact process of the 180 m high chimney was comprehensively analyzed. The results show that the chimney will experience multiple 'weight loss' and 'overweight' effects during the sit-down process, inducing compressive stress waves in the chimney. When the sit-down displacement is large, the broken reinforced concrete at the bottom can play a significant buffering effect, and the 'overweight' effect gradually weakens until the sit-down stops. The stress of the inner and outer sides of the chimney wall is obviously different in the process of collapsing and touching the ground. The waveform of the monitoring point of the piezoelectric ceramic sensor is divided into three stages, which specifically characterizes the evolution process of the explosion load and the impact of the chimney. The vibration induced by explosive explosion is mainly high-frequency vibration above 50 Hz, the vibration induced by chimney collapse is mainly low-frequency vibration below 10 Hz, and the vibration characteristics are obviously different. In the process of blasting demolition and collapse of high-rise reinforced concrete chimney, due to the impact of sitting down, the wall of the support tube is subjected to uneven force, resulting in the deviation of the collapse direction. In practical engineering, the control measures of chimney impact, blasting vibration, and collapse touchdown vibration should be fully strengthened to ensure the safety of the protection target around the blasting demolition object.

Development of Engineered CAR T Cells Targeting Tumor-Associated Glycoforms of MUC1 for the Treatment of Intrahepatic Cholangiocarcinoma.

Intrahepatic cholangiocarcinoma (ICC) is a common malignancy arising from the liver with limited 5-year survival. Thus, there is an urgency to explore new treatment methods. Chimeric antigen receptor T (CAR T) cell therapy is a very promising cancer treatment. Though, several groups have investigated CAR T cells targeting MUC1 in solid cancer models, Tn-MUC1-targeted CAR T cells have not yet to be reported in ICC. In this study, we confirmed Tn-MUC1 as a potential therapeutic target for ICC and demonstrated that its expression level was positively correlated with the poor prognosis of ICC patients. More importantly, we successfully developed effective CAR T cells to target Tn-MUC1-positive ICC tumors and explored their antitumor activities. Our results suggest the CAR T cells could specifically eliminate Tn-MUC1-positive ICC cells, but not Tn-MUC1-negative ICC cells, in vitro and in vivo. Therefore, our study is expected to provide new therapeutic strategies and ideas for the treatment of ICC.

Toripalimab combined with lenvatinib and GEMOX is a promising regimen as first-line treatment for advanced intrahepatic cholangiocarcinoma: a single-center, single-arm, phase 2 study.

Advanced intrahepatic cholangiocarcinoma (ICC) has a dismal prognosis. Here, we report the efficacy and safety of combining toripalimab, lenvatinib, and gemcitabine plus oxaliplatin (GEMOX) as first-line therapy for advanced ICC. Thirty patients with pathologically confirmed advanced ICC received intravenous gemcitabine (1 g/m2) on Days 1 and 8 and oxaliplatin (85 mg/m2) Q3W for six cycles along with intravenous toripalimab (240 mg) Q3W and oral lenvatinib (8 mg) once daily for one year. The expression of programmed death-ligand 1 (PD-L1) and genetic status was investigated in paraffin-embedded tissues using immunohistochemistry and whole-exome sequencing (WES) analysis. The primary endpoint was the objective response rate (ORR). Secondary outcomes included safety, overall survival (OS), progression-free survival (PFS), disease control rate (DCR) and duration of response (DoR). As of July 1, 2022, the median follow-up time was 23.5 months, and the ORR was 80%. Twenty-three patients achieved partial response, and one achieved complete response. Patients (21/30) with DNA damage response (DDR)-related gene mutations showed a higher ORR, while patients (14/30) with tumor area positivity ≥1 (PD-L1 staining) showed a trend of high ORR, but without significant difference. The median OS, PFS, and DoR were 22.5, 10.2, and 11.0 months, respectively. The DCR was 93.3%. Further, 56.7% of patients experienced manageable grade ≥3 adverse events (AEs), commonly neutropenia (40.0%) and leukocytopenia (23.3%). In conclusion, toripalimab plus lenvatinib and GEMOX are promising first-line regimens for the treatment of advanced ICC. A phase-III, multicenter, double-blinded, randomized study to validate our findings was approved by the National Medical Products Administration (NMPA, No. 2021LP01825).Trial registration Clinical trials: NCT03951597.

Nicotine Suppresses Phagocytic Ability of Macrophages by Regulating the miR-296-3p-SIRPα Axis.

Phagocytic ability of macrophage is responsible for tuberculosis infection. Nicotine has been shown to attenuate the phagocytic ability of macrophage; however, the underlying mechanism remains unclear. Here, we demonstrated that nicotine increased the message RNA (mRNA) and protein expression of signal regulatory protein alpha (SIRPα) and enhanced the stability of SIRPα mRNA in macrophage. Nicotine decreased the expression of microRNA (miR)-296-3p, which directly targeted the 3'-untranslated region (3'-UTR) of SIRPα mRNA in macrophage. Furthermore, nicotine inhibited the phagocytic ability of macrophage by regulating the miR-296-3p-SIRPα axis. Moreover, nicotine decreased miR-296-3p expression via increasing c-Myc expression in macrophage. Together, we found that nicotine attenuate the phagocytic ability of macrophage by regulating the c-Myc-miR-296-3p-SIRPα signal.