MRI-based pedicle bone quality score: correlation to quantitative computed tomography bone mineral density and its role in quantitative assessment of osteoporosis.

BACKGROUND CONTEXT: Bone quality in the pedicle region generally determines screw pullout strength, insertion torque, and vertebral body loading characteristics. Dual-energy X-ray absorptiometry (DEXA), as the gold standard for evaluating bone mineral density (BMD), cannot measure the BMD of specific parts, such as pedicle, and DEXA is limited in many ways. Recent studies have shown a correlation between the magnetic resonance imaging (MRI)-based vertebral bone quality (VBQ) score and BMD measured using DEXA or quantitative computed tomography (QCT). However, no studies have been reported on the MRI-based pedicle bone quality (PBQ) score. Moreover, few studies have investigated the relationship between MRI-based PBQ and osteoporosis. PURPOSE: To create a new site-specific MRI-based PBQ assessment method and assess its diagnostic capacity in patients with normal BMD and osteopenia/osteoporosis. STUDY DESIGN/SETTING: A retrospective study. PATIENT SAMPLE: A total of 156 patients underwent lumbar fusion surgery for chronic low back pain at our hospital between 2021 and 2022, with lumbar QCT and T1-weighted MRI performed before surgery. OUTCOME MEASURES: Correlation of the PBQ score with QCT BMD, and the association between the PBQ score and presence of osteopenia/osteoporosis. METHODS: BMD of the lumbar was calculated as the mean BMD of the L1 and L2 vertebral bodies on the basis of asynchronous QCT measurements. The PBQ score, which is the average of the bone quality values of both pedicles on the basis of site-specific T1-weighted sagittal MRI images, was calculated by dividing the median signal intensity of the L1-L4 pedicles by the signal intensity of the cerebrospinal fluid at the L3 level. The interobserver reliability of the PBQ score was assessed using the intraclass correlation coefficient (ICC). A receiver operating characteristic curve was drawn, and the area under the curve (AUC) was calculated to assess the predictive performance of PBQ for osteoporosis. The PBQ score was compared with QCT BMD, as the gold standard, using Pearson correlation analysis. RESULTS: In total, 156 patients participated in this study, including 51 in the Normal BMD group and 105 in the osteopenia/osteoporosis group. The PBQ score in the osteopenia/osteoporosis group was significantly higher than that in the normal BMD group (3.19±0.55 vs. 2.84±0.51, p<.001). The VBQ and PBQ scores were calculated by 2 authors and were in good agreement (intraclass correlation coefficient=0.949 and 0.929, respectively). Pearson's test showed a significant negative correlation between PBQ and QCT BMD (r=-0.4887, p<.001). The optimal cutoff PBQ score to differentiate patients with osteopenia/osteoporosis from those with normal BMD was 3.160, with a sensitivity of 66.7%, specificity of 72.5%, and AUC of 0.776. The PBQ score correlated more strongly with QCT BMD (r=-0.4887) than VBQ (r=-0.4078). CONCLUSIONS: In this study, we propose a novel, MRI-based pedicle-specific bone quality score. This is the first study to investigate the relationship between the PBQ score and QCT BMD. The PBQ score showed diagnostic utility, differentiating between patients with osteopenia/osteoporosis and those with normal BMD (AUC=0.776), and the PBQ score correlated more strongly with QCT BMD than VBQ.

Pediatric incarcerated inguinal hernia: Traditional open or laparoscopic-assisted approach?

The objective of this study was to compare the safety and efficacy of laparoscopic-assisted surgery and traditional open surgery for pediatric incarcerated inguinal hernia. A total of 58 pediatric patients with indirect incarcerated inguinal hernia between January 2014 and January 2020 were included in this study. The patients were divided into 2 groups; observational group who underwent laparoscopic-assisted surgery (n = 36), and a control group who underwent traditional open surgery (n = 22). The overall operation time, intraoperative blood loss, postoperative recovery time, length of hospital stay, occurrence of postoperative scrotal or vulvar hematomas, incidence of postoperative surgical site infection, and hernia recurrence were analyzed and compared between the 2 groups. Compared with the control group, the operation time (38.28 ±â€…5.90) minutes, intraoperative blood loss (1.15 ±â€…0.54 mL), postoperative recovery time (8.39 ±â€…1.42 h), and length of hospital stay (1.64 ±â€…0.59) were significantly lower in the observational group (P < .05). There was no incidence of scrotal or vulvar hematoma or surgical site infection in the observation group, which was significantly lower than that in the control group (P < .05). However, no statistically significant difference was found in the rate of postoperative hernia recurrence between the 2 groups (P > .05). In conclusion, laparoscopic-assisted surgery appears to be a safe and effective alternative approach to traditional open surgery for the treatment of pediatric incarcerated inguinal hernia. Its advantages include reduced trauma, faster recovery, shorter hospital stays, and fewer complications.

Lysine 2-hydroxyisobutyrylation proteomics analyses reveal the regulatory mechanism of CaMYB61-CaAFR1 module in regulating stem development in Capsicum annuum L.

Plant stems constitute the most abundant renewable resource on earth. The function of lysine (K)-2-hydroxyisobutyrylation (Khib), a novel post-translational modification (PTM), has not yet been elucidated in plant stem development. Here, by assessing typical pepper genotypes with straight stem (SS) and prostrate stem (PS), we report the first large-scale proteomics analysis for protein Khib to date. Khib-modifications influenced central metabolic processes involved in stem development, such as glycolysis/gluconeogenesis and protein translation. The high Khib level regulated gene expression and protein accumulation associated with cell wall formation in the pepper stem. Specially, we found that CaMYB61 knockdown lines that exhibited prostrate stem phenotypes had high Khib levels. Most histone deacetylases (HDACs, e.g., switch-independent 3 associated polypeptide function related 1, AFR1) potentially function as the "erasing enzymes" involved in reversing Khib level. CaMYB61 positively regulated CaAFR1 expression to erase Khib and promote cellulose and hemicellulose accumulation in the stem. Therefore, we propose a bidirectional regulation hypothesis of "Khib modifications" and "Khib erasing" in stem development, and reveal a novel epigenetic regulatory network in which the CaMYB61-CaAFR1 molecular module participating in the regulation of Khib levels and biosynthesis of cellulose and hemicellulose for the first time.

Integrative analyses of genetic characteristics associated with skeletal endothelial cells

Abstract The osseous vascular endothelium encompasses a vast intricate framework that regulates bone remodeling. Osteoporosis, an age-associated systemic bone disease, is characterized by the degeneration of the vascular architecture. Nevertheless, the precise mechanisms underpinning the metamorphosis of endothelial cells (ECs) with advancing age remain predominantly enigmatic. In this study, we conducted a systematic analysis of differentially expressed genes (DEGs) and the associated pathways in juvenile and mature femoral ECs, utilizing data sourced from the Gene Expression Omnibus (GEO) repositories (GSE148804) and employing bioinformatics tools. Through this approach, we successfully discerned six pivotal genes, namely Adamts1, Adamts2, Adamts4, Adamts14, Col5a1, and Col5a2. Subsequently, we constructed a miRNA-mRNA network based on miRNAs displaying differential expression between CD31hiEMCNhi and CD31lowEMCNlow ECs, utilizing online repositories for prediction. The expression of miR-466i-3p and miR-466i-5p in bone marrow ECs exhibited an inverse correlation with age. Our in vivo experiments additionally unveiled miR-466i-5p as a pivotal regulator in osseous ECs and a promising therapeutic target for age-related osteoporosis.

Comprehensive analysis of single cell and bulk data develops a promising prognostic signature for improving immunotherapy responses in ovarian cancer.

The tumor heterogeneity is an important cause of clinical therapy failure and yields distinct prognosis in ovarian cancer (OV). Using the advantages of integrated single cell RNA sequencing (scRNA-seq) and bulk data to decode tumor heterogeneity remains largely unexplored. Four public datasets were enrolled in this study, including E-MTAB-8107, TCGA-OV, GSE63885, and GSE26193 cohorts. Random forest algorithm was employed to construct a multi-gene prognostic panel and further evaluated by receiver operator characteristic (ROC), calibration curve, and Cox regression. Subsequently, molecular characteristics were deciphered, and treatments strategies were explored to deliver precise therapy. The landscape of cell subpopulations and functional characteristics, as well as the dynamic of macrophage cells were detailly depicted at single cell level, and then screened prognostic candidate genes. Based on the expression of candidate genes, a stable and robust cell characterized gene associated prognosis signature (CCIS) was developed, which harbored excellent performance at prognosis assessment and patient stratification. The ROC and calibration curves, and Cox regression analysis elucidated CCIS could serve as serve as an independent factor for predicting prognosis. Moreover, a promising clinical tool nomogram was also constructed according to stage and CCIS. Through comprehensive investigations, patients in low-risk group were charactered by favorable prognosis, elevated genomic variations, higher immune cell infiltrations, and superior antigen presentation. For individualized treatment, patients in low-risk group were inclined to better immunotherapy responses. This study dissected tumor heterogeneity and afforded a promising prognostic signature, which was conducive to facilitating clinical outcomes for patients with OV.

Association between platelet­to­lymphocyte ratio and serum prostate specific antigen.

There is evidence that the systemic inflammatory response may have an impact on prostate-specific antigen (PSA) levels. However, the relationship between the platelet-to-lymphocyte ratio (PLR) and PSA remains unclear. As a result, the relationship between PLR and PSA using the National Health and Nutrition Examination Survey (NHANES) database was examined. After the screening, 6,638 participants out of 52,186 in the NHANES survey conducted between 2001 to 2010 were suitable for the present study. The PLR was the independent variable in the present study, and PSA was the dependent variable. The selected subjects in the present study had an average age of 58.563±11.848 years. After controlling for covariates, the results showed that with every increase in PLR, the PSA concentration increased by 0.004 ng/ml (0.001, 0.007). This difference was statistically significant. Furthermore, a smoothing curve based on a fully adjusted model was created to investigate the possibility of a linear relationship between PLR and PSA concentration in men from USA. In men from USA, an independent and positive correlation between PLR and PSA was identified, which could potentially result in overdiagnosis of asymptomatic prostate cancer in populations with higher PLR levels.

AARS2 as a novel biomarker for prognosis and its molecular characterization in pan-cancer.

INTRODUCTION: The mitochondrial alanyl-tRNA synthetase 2 (AARS2) as one of aminoacyl-tRNA synthases (ARSs) performs amino acid transportation and involves protein synthesis. However, its role in cancer remains largely unexplored. METHODS: In this study, more than 10,000 samples were enrolled to explore genomic alterations, biological function, prognosis, and clinical treatment based on AARS2 across pan-cancer. The molecular characterization of AARS2 was confirmed in hepatocellular carcinoma (HCC) using proteomics analysis, quantitative real-time PCR, western blotting, immunohistochemical staining, and cell experiments. RESULTS: For genomic landscape, the AARS2 was dramatically upregulated in multiple cancers, which might be mainly caused by copy number alteration rather than mutation and methylation. The abnormal expression of AARS2 was prominently associated with activity of cancer pathways and performed oncogenic roles in most cancers. Systematic experiments in vitro substantiated the elevated expression of AARS2, and the deficiency of it inhibited cell proliferation and cell migration in HCC. Meanwhile, our findings suggested that AARS2 could serve as a novel promising and stable biomarker for assessing prognosis and immunotherapy. Moreover, a variety of therapeutic drugs and targeted pathways were proposed for cancer treatment, which might enhance clinical efficacy. CONCLUSION: The AARS2 could serve as a new oncogenic gene that promotes cell proliferation and migration in HCC. The comprehensive investigations increased the understanding of AARS2 across human cancers and generated beginning insights of AARS2 in genomic landscape, molecular biological function, prognosis, and clinical treatment.

A Comparison of Corpectomy ACDF Hybrid Procedures with Nano-Hydroxyapatite/Polyamide 66 Cage and Titanium Mesh Cage for Multi-level Degenerative Cervical Myelopathy: A Stepwise Propensity Score Matching Analysis.

OBJECTIVE: Previous studies have found satisfactory clinical results with the nano-hydroxyapatite/polyamide 66 (n-HA/PA66) cage to reconstruct the stability of anterior cervical column. However, studies evaluating the long-term outcomes of the n-HA/PA66 cage in multi-level degenerative cervical myelopathy (MDCM) have not been reported. This study aims to compare the outcomes of corpectomy anterior cervical discectomy and fusion (ACDF) hybrid procedures between the n-HA/PA66 cage and titanium mesh cage (TMC) to treat MDCM. METHODS: After the screening for eligibility, this retrospective study involved 90 patients who underwent corpectomy ACDF hybrid (CACDFH) procedure from June 2013 to June 2018. The CACDFH procedure is the combination of ACDF and anterior cervical corpectomy and fusion (ACCF). According to the cage utilized, we categorized patients into a n-HA/PA66 cage group and a TMC group. Then, stepwise propensity score matching (PSM) was performed to maintain comparable clinical data between groups. All the patients were followed up ≥4 years and the longest follow-up time was 65.43 (±11.49) months. Cage subsidence, adjacent segment degeneration (ASD), segmental height (SH), segmental angle (SA), cervical lordosis (CL), and clinical data (visual analogue scale [VAS] and Japanese Orthopaedic Association [JOA] score) was evaluated preoperatively, at 1 week, and at the final surgery follow-up. The independent student's t test and chi-square test were applied to compare the differences between groups. RESULTS: Through PSM analysis, 25 patients from the n-HA/PA66 group were matched to 25 patients in the TMC group. The occurrence of ASD was 16.0% (4/25) in the n-HA/PA 66 group, which was significantly less than in the TMC group at 44.0% (11/25) (p = 0.031). Moreover, the cage subsidence rate was significantly higher in the TMC group as compared to the n-HA/PA 66 group (40.0% vs. 12.0%, p = 0.024). But there was no significant difference in SH, SA, and CL at any time after surgery as determined through follow-up. The VAS and JOA scores significantly improved in both groups at 3 months postoperative and at final follow-up. However, there were no significant differences in the VAS and JOA score at any time between the two groups in preoperative (p > 0.05). CONCLUSION: The n-HA/PA66 cage is associated with lower rate of cage subsidence and ASD than the TMC in the treatment of MDCM. The n-HA/PA66 cage could be superior to the TMC in corpectomy ACDF hybrid procedures.

Expression of TXLNA in brain gliomas and its clinical significance: a bioinformatics analysis.

BACKGROUND: To analyze the expression of TXLNA in brain gliomas and its clinical significance. METHODS: Gene Expression Profiling Interactive Analysis（GEPIA）and Chinese Glioma Genome Atlas（CGGA）databases were retrieved as the methods. To assess the disparity between TXLNA expression in glioma and normal brain tissue. The Kaplan-Meier survival curve was employed to preliminarily evaluate the survival curves of the high and low expression groups, this was done for investigate the correlation between TXLNA expression level and the survival and prognosis of glioma. A Cox proportional regression risk model of multivariate nature was employed to evaluate the elements impacting the survival and prognosis of glioma. Gene pool enrichment analysis（GSEA）was used to investigate the related function of TXLNA in glioma. A Pearson correlation test and co-expression analysis were employed to identify the genes most associated with TXLNA expression. RESULT: The enrichment analysis results were observably enriched in signal pathways for instance the cell cycle and completion and coordination cascade pathways, and it is evident that high expression of TXLNA in gliomas is related to a poor survival and a bad patient prognosis, thus making it an independent prognostic factor for gliomas. Genes such as STK40 and R1MS1 are significantly correlated with TXLNA, playing a synergistic or antagonistic role. CONCLUSIONS: The prognosis of GBM patients is strongly linked to the high expression of TXLNA, which may be a viable therapeutic target for curbing cancer progression and creating new immunotherapies for GBM.

Clinical Outcomes of Isobar TTL System with Isthmic Bone Grafting and Pedicle Screw-Vertebral Plate Hook with Direct Repair of Defect for Lumbar Spondylolysis: A Matched-Pair Case Control Study.

OBJECTIVE: Although direct isthmic repair, such as PSVPH, did not affect the mobility of the fixed segment and adjacent segment, it has a relatively low rate of isthmic fusion compared with conventional fusion. The Isobar TTL dynamic internal fixation system has been widely used in clinical practice and has achieved satisfactory clinical results. However, the use of the Isobar TTL system in combination with direct isthmic repair for lumbar spondylolysis has rarely been reported. The aim of this study was to compare the clinical and radiologic outcomes between patients who underwent Isobar TTL system and PSVPH with direct repair of defect for lumbar spondylolysis. METHODS: Stepwise propensity score matching (PSM) for age and sex were performed to keep comparable clinical data between groups in this retrospective and matched-pair case control study. A total of 50 patients diagnosed with lumbar spondylolysis underwent surgical implantation of the Isobar TTL group (n = 25) or PSVPH group (n = 25) from June 2009 to June 2016. Clinical outcomes were assessed using the Oswestry disability index (ODI), and visual analog score (VAS). Radiographic evaluations included range of motion (ROM) and the disc heights of stabilized segment and adjacent segment, adjacent segment degeneration (ASD) and bony fusion. Three-dimensional reconstruction of lumbar CT scan was obtained to evaluate bone fusion of the isthmic at final follow-up. The independent Student's t test and chi-square test were applied to compare the differences between groups. RESULTS: A total of 25 patients from TTL group were matched to 25 patients in PSVPH group for age, sex, body mass index (BMI), defect side, spondylolisthesis meyerding, and follow-up duration. The intervertebral space height (IH) of stabilized segment at postoperative 1 week and final follow-up in the TTL group was higher than those in the PSVPH group, respectively (P = 0.030; P = 0.013). The ROM of stabilized segment at final follow-up in the TTL group was significantly lower than that in the PSVPH group (P < 0.001). The bony fusion rate at the final follow-up was 88.0% (22/25 cages) in the TTL group and 80.0% (20/25 cages) in the PSVPH group. The ODI score at final follow-up in the TTL group was significantly lower than that in the PSVPH group (P = 0.007). CONCLUSION: Overall, our data suggest that the Isobar TTL system outcomes are comparable to those in the PSVPH, with a similar high bony fusion rate as PSVPH, especially its wider indications as a new surgery.

Long-term outcomes of the nano-hydroxyapatite/polyamide-66 cage versus the titanium mesh cage for anterior reconstruction of thoracic and lumbar corpectomy: a retrospective study with at least 7 years of follow-up.

BACKGROUND: The nano-hydroxyapatite/polyamide-66 (n-HA/PA66) cage is a biomimetic cage with a lower elastic modulus than the titanium mesh cage (TMC). This study aimed to compare the long-term outcomes of the n-HA/PA66 cage and TMC in the anterior reconstruction of thoracic and lumbar fractures. METHODS: We retrospectively studied 113 patients with acute traumatic thoracic or lumbar burst fractures, comprising 60 patients treated with the TMC and 53 treated with the n-HA/PA66 cage for anterior reconstruction following single-level corpectomy. The radiographic data (cage subsidence, fusion status, segmental sagittal alignment) and clinical data (visual analogue scale (VAS) for pain and Oswestry Disability Index (ODI) for function) were evaluated preoperatively, postoperatively, and at final follow-up after a minimum 7-year period. RESULTS: The n-HA/PA66 and TMC groups had similar final fusion rates (96.2% vs. 95.0%). The cage subsidence at final follow-up was 2.3 ± 1.6 mm with subsidence of more than 3 mm occurring in 24.5% in the n-HA/PA66 group, which was significantly lower than the respective values of 3.9 ± 2.5 mm and 58.3% in the TMC group. The n-HA/PA66 group also had better correction of the bisegmental kyphotic angle than the TMC group (7.1° ± 7.5° vs 1.9° ± 8.6°, p < 0.01), with lower loss of correction (2.9° ± 2.5° vs 5.2° ± 4.1°, p < 0.01). The mean ODI steadily decreased after surgery in both groups. At final follow-up, the ODI and VAS were similar in the TMC and n-HA/PA66 groups. CONCLUSIONS: The n-HA/PA66 cage is associated with excellent radiographic fusion, better maintenance of the height of the fused segment, and better correction of kyphosis than the TMC during 7 years of follow-up after one-level anterior corpectomy. With the added benefit of radiolucency, the n-HA/PA66 cage may be superior to the TMC in anterior reconstruction of thoracic or lumbar fractures.

m6 A reader YTHDF3 triggers the progression of hepatocellular carcinoma through the YTHDF3/m6 A-EGFR/STAT3 axis and EMT.

Hepatocellular carcinoma (HCC) is the sixth most common cancer and the fourth leading cause of tumor-related deaths worldwide. N6-methyladenosine (m6 A) mediates RNA metabolism in tumor biology. However, the regulatory role of YTHDF3, an m6 A reader, in HCC progression and its underlying mechanisms remains unclear. Therefore, this study aims to investigate the oncogenic effect of YTHDF3 on HCC progression via the epigenetic regulation of m6 A-modified mRNAs. The expression levels of YTHDF3 in HCC tissues and matched adjacent liver tissues were detected using western blot analysis, immunohistochemistry, and quantitative real-time polymerase chain reaction. The function of YTHDF3 in HCC progression and its underlying mechanisms have been studied both in vitro and in vivo. YTHDF3 expression was significantly higher in HCC tissues than in paracancerous liver tissues. YTHDF3 was also significantly upregulated in HCC with microvascular invasion (MVI) compared to that in HCC without MVI. YTHDF3 overexpression facilitated the proliferation, invasion, and migration of HCC cells both in vitro and in vivo. However, the YTHDF3 knockdown resulted in an inverse trend. Mechanistically, YTHDF3 enhanced the translation and stability of the m6 A-modified epidermal growth factor receptor (EGFR) mRNA, which activated the downstream EGFR/signal transducer and activator of transcription 3 (STAT3) and epithelial-mesenchymal transition (EMT) oncogenic pathways. YTHDF3 enhanced the stability and translation of m6 A-modified EGFR mRNA and stimulated HCC progression via the YTHDF3/m6 A-EGFR/STAT3 and EMT pathways. These findings reveal that YTHDF3 plays a significant role in regulating HCC progression, suggesting a promising and novel target for HCC treatment.

Probiotics Alleviate Chemotherapy-Associated Intestinal Mucosal Injury via the TLR4-NFκB Signaling Pathway.

Introduction: Temozolomide (TMZ) induces intestinal mucosa injury that cannot be fully counteracted by supportive treatment. Probiotics regulate gut microbial composition and the host immune system and may alleviate this side effect. We aimed to investigate the potential and mechanism of Lactobacillus rhamnosus GG (LGG) in relieving intestinal mucosal injury induced by TMZ. Methods: Glioblastoma mice were divided into four groups: CON (control), LGG (109 CFU/mL, treated for 7 days), TMZ (50 mg/kg·d, treated for 5 days), LGG+TMZ (LGG for 7 days and TMZ subsequently for 5 days). Body weight, food intake, and fecal pH were recorded. Intestinal tissue samples were collected 1 day after the end of TMZ treatment. Degree of damage to intestine, expression of IL1ß, IL6, TNFα, and IL10 in jejunum were determined. Levels of tight-junction proteins (ZO1, occludin), TLR4, IKKß, IκBα, and P65 with their phosphorylation in jejunum were measured. Results: Decreases in body weight, food intake, spleen index in the TMZ group were mitigated in the LGG+TMZ group, and the degree of intestinal shortening and damage to jejunum villus were also alleviated. The expression of tight-junction proteins in the LGG+TMZ group was significantly greater than that in the TMZ group. IκBα in intestinal tissue significantly decreased in the TMZ group, phos-IKKß and phos-P65 increased compared to the CON group, and LGG reversed such changes in IκBα and phos-P65 in the LGG+TMZ group. Intestinal inflammatory cytokines were significantly increased in the TMZ group, but lower in the LGG+TMZ group. Moreover, expression of TLR4 in LGG group was significantly lower than that in the CON group. LGG inhibited the rise of TLR4 after TMZ in the LGG+TMZ group compared to the TMZ group. Conclusion: LGG inhibits the activation of the TLR4-NFκB pathway and alleviates intestinal mucosal inflammation induced by TMZ, thereby protect the jejunum villi and mucosal physical barrier.

Local GHR roles in regulation of mitochondrial function through mitochondrial biogenesis during myoblast differentiation.

BACKGROUND: Myoblast differentiation requires metabolic reprogramming driven by increased mitochondrial biogenesis and oxidative phosphorylation. The canonical GH-GHR-IGFs axis in liver exhibits a great complexity in response to somatic growth. However, the underlying mechanism of whether local GHR acts as a control valve to regulate mitochondrial function through mitochondrial biogenesis during myoblast differentiation remains unknown. METHODS: We manipulated the GHR expression in chicken primary myoblast to investigate its roles in mitochondrial biogenesis and function during myoblast differentiation. RESULTS: We reported that GHR is induced during myoblast differentiation. Local GHR promoted mitochondrial biogenesis during myoblast differentiation, as determined by the fluorescence intensity of Mito-Tracker Green staining and MitoTimer reporter system, the expression of mitochondrial biogenesis markers (PGC1α, NRF1, TFAM) and mtDNA encoded gene (ND1, CYTB, COX1, ATP6), as well as mtDNA content. Consistently, local GHR enhanced mitochondrial function during myoblast differentiation, as determined by the oxygen consumption rate, mitochondrial membrane potential, ATP level and ROS production. We next revealed that the regulation of mitochondrial biogenesis and function by GHR depends on IGF1. In terms of the underlying mechanism, we demonstrated that IGF1 regulates mitochondrial biogenesis via PI3K/AKT/CREB pathway. Additionally, GHR knockdown repressed myoblast differentiation. CONCLUSIONS: In conclusion, our data corroborate that local GHR acts as a control valve to enhance mitochondrial function by promoting mitochondrial biogenesis via IGF1-PI3K/AKT/CREB pathway during myoblast differentiation. Video Abstract.