Association between circulating cell-free mitochondrial DNA and inflammation factors in noninfectious diseases: A systematic review.

OBJECTIVE: This study aimed to assess the correlation between the circulating cell-free mitochondria DNA and inflammation factors in noninfectious disease by meta-analysis of data from eligible studies. MATERIALS AND METHODS: Through a comprehensive searching of pubmed, embase, web of science, cochrane from establishment of the database to October 31, 2022, studies were selected that investigated the association of circulating cell free mitochondria DNA with inflammatory factors in non-infectious diseases. Studies that met the inclusion criteria and were published in English or Chinese were included. Data of each correlation coefficients were extracted from the paper and 95% confidence intervals were calculated. Sensitivity and heterogeneity tests were carried out for each data. RESULTS: A total of 660 articles were retrieved and 22 were included in this meta-analysis, including 2600 patients. A fixed effects model was employed to examine ISS and IL-8, others were analyzed using random effects models. The correlation coefficient between mtDNA and ISS score was 0.37 (95%CI = [0.232;0.494]), p<0.0001, heterogeneity I2 = 46%, p = 0.11). The correlation coefficients between mtDNA and inflammatory factors are as follows: TNFα, 0.405 [(95%CI = [0.253;0.538], p<0.0001, heterogeneity I2 = 77%, p = 0.0001]. IL-6, 0.469 [(95%CI = [0.296;0.612]), p = 0.0001, heterogeneity I2 = 93%, p<0.0001]. CRP, 0.333[(95%CI = [0.149;0.494]), p = 0.005, heterogeneity I2 = 85%, p<0.0001]. IL-8, 0.343[(95%CI = [0.233;0.524]), p = 0.001, heterogeneity I2 = 50%, p = 0.09]. PCT, 0.333 [(95%CI = [0.06;0.64]), p = 0.09,heterogeneity I2 = 64%,p = 0.06]. There were no significant publication bias for TNFα, IL-6 and CRP. CONSLUSION: Circulating cell free mtDNA was moderate positively correlated with the expression of inflammatory factors and the degree of trauma.

Comparing two surgical approaches for treating multilevel cervical spondylotic myelopathy: A meta-analysis.

PURPOSE: This meta-analysis aims to evaluate the therapeutic efficacy of anterior versus posterior surgical approaches for multisegment cervical spondylotic myelopathy (MCSM). METHODS: Eligible studies published between the period of January 2001 and April 2022 and comparing the anterior and posterior surgical approaches for treating cervical spondylotic myelopathy were retrieved from the PubMed, Web of Science, Embase, and Cochrane databases. RESULTS: A total of 17 articles were selected based on the inclusion and exclusion criteria. This meta-analysis failed to show any significant difference in the duration of surgery, the hospitalization time, or the improvement in the Japanese Orthopedic Association score between the anterior and posterior approaches. The anterior approach, however, exhibited increased efficacy in the improvement of the neck disability index, reduction in the visual analog scale for cervical pain, and improvement in the cervical curvature compared with the posterior approach. CONCLUSION: Bleeding was also less with the anterior surgical approach. The posterior approach provided a significantly higher range of motion of the cervical spine and showed fewer postoperative complications compared with the anterior approach. While both the surgical approaches have good clinical outcomes and show postoperative neurological function improvement, the meta-analysis shows that both anterior and posterior approaches have certain merits and shortcomings. A meta-analysis of a larger number of randomized controlled trials with longer follow-up can conclusively determine which of the surgical approaches is more beneficial in the treatment of MCSM.

Adiponectin protects skeletal muscle from ischaemia-reperfusion injury in mice through miR-21/PI3K/Akt signalling pathway.

Previous studies have confirmed that adiponectin (APN) plays a protective role in myocardial ischaemia-reperfusion (IR) injury, and the aim of this study was to investigate its effect on skeletal muscle. ELISA was used to detect the levels of Creatinine Kinase (CK), LDH, SOD and MDA in the plasma of the lower limbs of mice, and the levels of IL-6, IL-1ß and TNF-α in the gastrocnemius. Quantitative PCR was used to detect the expression level of miR-21. TUNEL staining was used to detect the apoptosis of the gastrocnemius. The expression levels of apoptosis proteins, autophagy marker proteins and downstream target genes of miR-21 in gastrocnemius were detected by Western Blot. The results of this study revealed that APN levels were significantly reduced in gastrocnemius of IR mice. The oxidative stress, inflammatory response, apoptosis and autophagy induced by IR were significantly ameliorated by APN injection. The above effects of APN may be achieved through miR-21/PI3K signalling pathway, as found by interfering gene expression levels with miRNA antagomir and lentiviral injection. Taken together, our study revealed that APN protects skeletal muscle from IR injury through miR-21 /PI3K/Akt signalling pathway through inhibiting inflammatory response, apoptosis and autophagy.

Photoacoustic microscopy: a novel approach for studying perforator skin flap in a mouse model.

BACKGROUND: A comprehensive understanding of cutaneous microvessels is key to the design and use of the perforator skin flap. Compared with the various imaging technologies that have been applied in the clinical practice of the perforator skin flap, photoacoustic microscopy (PAM) is a very promising noninvasive imaging modality with high resolution and deep penetration in biological tissues. METHODS: PAM was employed to explore its multiple applications in a perforator skin flap. The following experiments were then conducted in 3 parts. In part 1, 7 mice were used to obtain the preoperative perforator mapping on the mouse back. In parts 2 and 3, 7 mice were used to design and harvest the multiterritory perforator flap. The status of the flap and the morphological changes of choke vessels were subsequently observed by PAM at several time points. RESULTS: The results showed that PAM could visualize and assess the vascular physiological and pathological conditions of the skin tissue in real time in vivo with high spatial and temporal resolution. It could also provide preoperative perforator mapping, including the total number of perforators, localization, vascular territories, and diameter. Furthermore, it could offer a quantitative, objective method to monitor the status of the perforator skin flap, and was capable of noninvasive characterization of the changes of choke vessels that play an important role in multiterritory perforator skin flap expansion and survival. CONCLUSIONS: PAM has great potential to be an effective and precise quantitative imaging tool for perforator skin flap research, such in as flap design, monitoring, and choke vessel observation.

MiR-144-5p, an exosomal miRNA from bone marrow-derived macrophage in type 2 diabetes, impairs bone fracture healing via targeting Smad1.

BACKGROUND: Patients with diabetes have an increased risk of nonunion and delayed union of fractures. Macrophages have been shown as a key player in diabetic complications. However, it remains obscure how diabetic milieu affects macrophage-derived exosomes and its implications on osteogenic differentiation of BMSCs. In this study, we aim to define the impact of diabetic milieu on macrophage-derived exosomes, role of extracellular vesicles in intercellular communication with BMSCs, and subsequent effects on osteogenic differentiation and fracture repair. RESULTS: The osteogenic potential and the ability of fracture repair of exosomes derived from diabetic bone marrow-derived macrophages (dBMDM-exos) were revealed to be lower, as compared with non-diabetic bone marrow-derived macrophages (nBMDM-exos) in vitro and in vivo. Interestingly, miR-144-5p levels were sharply elevated in dBMDM-exos and it could be transferred into BMSCs to regulate bone regeneration by targeting Smad1. In addition, the adverse effects of dBMDM-exos on the osteogenic potential and the ability of fracture repair were reversed through the suppression of miR-144-5p inhibition in vitro and vivo. CONCLUSIONS: The results demonstrated an important role of exosomal miR-144-5p in bone regeneration, offering insight into developing new strategy for the improvement of fracture healing in patients with diabetes mellitus.

EWS-FLI1-targeting peptide identifies Ewing sarcoma tumor boundaries and lymph node metastasis via near-infrared imaging.

Ewing sarcoma (ES) is one of the most aggressive types of pediatric tumors. The lack of tools for the identification of ES has largely hindered clinical diagnosis and the improvement of treatment. To address this challenge, we synthesized a near-infrared (NIR) fluorescent probe (CS2-N-E9R) that targets the ES-specific fusion protein EWS-FLI1 (E/F). This probe exhibited specific and high binding affinity to E/F. Further studies in animal models showed that CS2-N-E9R can be used to identify the boundaries of ES and lymph node metastases under a complex biological environment. These results demonstrate that CS2-N-E9R is a promising probe for early diagnosis and surgical guidance of ES through molecularly targeted NIR imaging.