Multimodal cell atlas of the ageing human skeletal muscle.

Muscle atrophy and functional decline (sarcopenia) are common manifestations of frailty and are critical contributors to morbidity and mortality in older people1. Deciphering the molecular mechanisms underlying sarcopenia has major implications for understanding human ageing2. Yet, progress has been slow, partly due to the difficulties of characterizing skeletal muscle niche heterogeneity (whereby myofibres are the most abundant) and obtaining well-characterized human samples3,4. Here we generate a single-cell/single-nucleus transcriptomic and chromatin accessibility map of human limb skeletal muscles encompassing over 387,000 cells/nuclei from individuals aged 15 to 99 years with distinct fitness and frailty levels. We describe how cell populations change during ageing, including the emergence of new populations in older people, and the cell-specific and multicellular network features (at the transcriptomic and epigenetic levels) associated with these changes. On the basis of cross-comparison with genetic data, we also identify key elements of chromatin architecture that mark susceptibility to sarcopenia. Our study provides a basis for identifying targets in the skeletal muscle that are amenable to medical, pharmacological and lifestyle interventions in late life.

Designing a structure-function alphabet of helix based on reduced amino acid clusters.

Several simple secondary structures could form complex and diverse functional proteins, meaning that secondary structures may contain a lot of hidden information and are arranged according to certain principles, to carry enough information of functional specificity and diversity. However, these inner information and principles have not been understood systematically. In our study, we designed a structure-function alphabet of helix based on reduced amino acid clusters to describe the typical features of helices and delve into the information. Firstly, we selected 480 typical helices from membrane proteins, zymoproteins, transcription factors, and other proteins to define and calculate the interval range, and the helices are classified in terms of hydrophilicity, charge and length: (1) hydrophobic helix (≤43%), amphiphilic helix (43%∼71%), and hydrophilic helix (≥71%). (2) positive helix, negative helix, electrically neutral helix and uncharged helix. (3) short helix (≤8 aa), medium-length helix (9-28 aa), and long helix (≥29 aa). Then, we designed an alphabet containing 36 triplet codes according to the above classification, so that the main features of each helix can be represented by only three letters. This alphabet not only preliminarily defined the helix characteristics, but also greatly reduced the informational dimension of protein structure. Finally, we present an application example to demonstrate the value of the structure-function alphabet in protein functional determination and differentiation.

Identification of differentially expressed autophagy-related genes in cases of intracranial aneurysm: Bioinformatics analysis.

OBJECTIVE: Recent research indicates that autophagy is essential for the rupture of intracranial aneurysm (IA). This study aimed to examine and validate potential autophagy-related genes (ARGs) in cases of IA using bioinformatics analysis. METHODS: Two expression profiles (GSE54083 and GSE75436) were obtained from the Gene Expression Omnibus database. Differentially expressed ARGs (DEARGs) in cases of IA were screened using GSE75436, and enrichment analysis and Protein-Protein Interaction (PPI) networks were used to identify the hub genes and related pathways. Furthermore, a novel predictive diagnostic signature for IA based on the hub genes was constructed. The area under the Receiver Operating Characteristic curve (AUC) was used to evaluate the signature performance in GSE75436. RESULTS: In total, 75 co-expressed DEARGs were identified in the GSE75436 and GSE54083 dataset (28 upregulated and 47 downregulated genes). Enrichment analysis of DEARGs revealed several enriched terms associated with proteoglycans in cancer and human immunodeficiency virus 1 infection. PPI analysis revealed interactions between these genes. Hub DEARGs included insulin-like growth factor 1, clusters of differentiation 4, cysteine-aspartic acid protease 8, Bcl-2-like protein 11, mouse double mutant 2 homolog, toll-like receptor 4, growth factor receptor-bound protein 2, Jun proto-oncogene, AP-1 transcription factor subunit, hypoxia inducible factor 1 alpha, and erythroblastic oncogene B-2. Notably, the signature showed good performance in distinguishing IA (AUC = 0.87). The sig calibration curves showed good calibration. CONCLUSION: Bioinformatic analysis identified 75 potential DEARGs in cases of IA. This study revealed that IA is affected by autophagy, which could explain the pathogenesis of IA and aid in its diagnosis and treatment. However, future research with experimental validation is necessary to identify potential DEARGs in cases of IA.

miRNA Therapy in Laboratory Models of Acute Spinal Cord Injury in Rodents: A Meta-analysis.

miRNA therapy is popularly investigated in treating acute spinal cord injury (SCI) and offers a significant prospect for the treatment of acute SCI. We aimed to provide pre-clinical validations of miRNA in the treatment of SCI. A systematic search of EMBASE, PubMed, Web of Science, the Cochrane Library, and Scopus databases was performed. Rats, which were the most used animals (70%, n = 46 articles), receiving miRNA therapy got prominent recovery in SCI models [BBB score, SMD 3.90, 95% CI 3.08-4.73, p < 0.01]. Locomotor function of fore and hind limbs in SCI mice receiving miRNA therapy (30%, n = 19 articles) [grip strength, SMD 3.22, 95% CI 2.14-4.26; p < 0.01; BBB score, SMD 3.47, 95% CI 2.38-4.56, p < 0.01; BMS, SMD 2.27, 95% CI 1.34-3.20, p < 0.01] also recovered better than mice in control group. Then, we conducted the subgroup analysis and did find that high-quality articles trended to report non-therapeutic effect of miRNA. Furtherly, we analyzed 46 miRNAs, including 9 miRNA families (miR-21-5p/34a-3p/124-3p/126-3p/223-3p/543-3p/30-3p/136-3p/15-5p), among which miR-30-3p/136-3p/15-5p family were not effective in recovering locomotor function of rats. Conclusively, miRNAs are curative drugs for SCI, however, appropriate miRNA carrier and which miRNA is the most efficacious for SCI should be furtherly investigated.

Effects of Transcranial Direct Current Stimulation on Graph Naming Function and Brain Connectivity in Post-Infarction Aphasia Patients: An fMRI Study.

OBJECTIVE: The study aimed to investigate the mechanisms of impairment and recovery in graph naming functions among patients with aphasia due to cerebral infarction. Specifically, the study compared immediate effects of transcranial Direct Current Stimulation (tDCS) treatment in patients at different stages post-infarction: the acute phase and the recovery period. METHODS: Twenty-eight patients were selected, consisting of 16 in the acute phase (AP) and 12 in the recovery period (RP), along with 18 healthy controls. Both patient groups underwent two weeks of tDCS treatment. Post-treatment changes in functional connectivity (FC) within language-related brain regions, as well as in graph naming abilities, were assessed in both patient groups. RESULTS: Both AP and RP groups exhibited significant improvements in graph naming ability following tDCS treatment. Compared to healthy controls, patients showed decreased functional connectivity in multiple brain regions of both hemispheres, particularly in the dominant hemisphere. Post-treatment assessments revealed significant increases in functional connectivity within the bilateral frontotemporal lobes for both AP and RP groups, and within the bilateral temporo-occipital regions for the AP group. Moreover, the RP group demonstrated decreased functional connectivity in the left temporal lobe post-treatment, which had shown increased functional connectivity pre-treatment. CONCLUSIONS: This study suggests that tDCS can effectively enhance graph naming functions in patients with post-infarction aphasia. The therapeutic effects appear to be mediated by enhancing functional connectivity within bilateral frontotemporal lobes.

Heparin-induced persistent hyperthermia with recurrent hyponatremia in hip fracture: Case report and review of literature.

WHAT IS KNOWN AND OBJECTIVE: Heparin is a commonly used anticoagulant in clinic. Persistent hyperthermia with recurrent hyponatremia caused by heparin is an extremely rare drug fever, which is difficult to judge in the early stage and is often misdiagnosed. CASE SUMMARY: A 74-year-old elderly woman was admitted to our hospital due to left hip pain with limited mobility for 9 h. She was diagnosed with a femoral neck fracture, and continuous heparin anticoagulation was initiated. On the night of surgery, the patient developed high fever with a drop in the serum sodium concentration. Based on the patient's symptoms, signs, and results of the laboratory tests, postoperative absorptive heat and infectious fever were ruled out. After heparin discontinuation, her temperature and serum sodium concentration returned to the baseline levels. WHAT IS NEW AND CONCLUSION: Heparin can cause persistent or recurrent hyponatremia and should be considered in the identification of the aetiology this condition.

Opioid doses required for pain management in lung cancer patients with different cholesterol levels: negative correlation between opioid doses and cholesterol levels.

BACKGROUND: Pain management has been considered as significant contributor to broad quality-of-life improvement for cancer patients. Modulating serum cholesterol levels affects analgesia abilities of opioids, important pain killer for cancer patients, in mice system. Thus the correlation between opioids usages and cholesterol levels were investigated in human patients with lung cancer. METHODS: Medical records of 282 patients were selected with following criteria, 1) signed inform consent, 2) full medical records on total serum cholesterol levels and opioid administration, 3) opioid-naïve, 4) not received/receiving cancer-related or cholesterol lowering treatment, 5) pain level at level 5-8. The patients were divided into different groups basing on their gender and cholesterol levels. Since different opioids, morphine, oxycodone, and fentanyl, were all administrated at fixed low dose initially and increased gradually only if pain was not controlled, the percentages of patients in each group who did not respond to the initial doses of opioids and required higher doses for pain management were determined and compared. RESULTS: Patients with relative low cholesterol levels have larger percentage (11 out of 28 in female and 31 out of 71 in male) to not respond to the initial dose of opioids than those with high cholesterol levels (0 out of 258 in female and 8 out of 74 in male). Similar differences were obtained when patients with different opioids were analyzed separately. After converting the doses of different opioids to equivalent doses of oxycodone, significant correlation between opioid usages and cholesterol levels was also observed. CONCLUSIONS: Therefore, more attention should be taken to those cancer patients with low cholesterol levels because they may require higher doses of opioids as pain killer.

Allograft ligament transplantation in anterior cruciate ligament reconstruction patients with meniscal tears.

BACKGROUND: It currently remains unclear whether the meniscal repair clinical results were affected by the graft used in anterior cruciate ligament (ACL) reconstruction. This retrospective study designed to evaluate the difference in clinical outcomes of meniscal repair using autograft and allograft for the ACL reconstruction. METHODS: The injury of the ACL and meniscus was evaluated with MRI and treated simultaneously. One hundred and eighty-nine cases were initially fulfilled the study criteria, and had the surgery in the period June 2007 and July 2010. Thirty-four patients were lost to follow-up. Seventy-five patients underwent meniscus repair with autograft reconstruction of the ACL (autograft group) and 80 patients underwent meniscus repair with allograft reconstruction of the ACL (allograft group). RESULTS: The meniscus healing rate based on the clinical examination of Barrett's criteria was 81.3 % (61/75) in the autograft group and 80.0 % (64/80) in the allograft (P > 0.05). There was no significant difference in the Lysholm scores in the allograft group compared to the allograft group (89.1 ± 10.6 versus 88.7 ± 11.2, P > 0.05). The values of immunoglobulin's and complements (IgG, IgA, IgM, C3 and C4) were not significantly different between the two groups (P > 0.05). CONCLUSION: The data support our assumption that patients undergoing meniscal repair associated with ACL reconstruction with allograft had good clinical outcomes. Although allograft implantation induces an immunological response on a subclinical level, there were no signs of allograft affecting the nature of meniscus healing.

Probiotic consumption and hepatic steatosis: results from the NHANES 2011-2016 and Mendelian randomization study.

Background: Recent research showed that probiotics treatment may reduce insulin resistance, regulate lipid metabolism, raise liver enzyme levels, and ameliorate inflammation in individuals with metabolic associated fatty liver disease (MAFLD). However, the possible effects of probiotic use on the progression of hepatic steatosis (HS) have not been identified. The purpose of this study was to investigate this in a large population database. Methods: The cross-sectional research was conducted among adults with complete data on probiotic yogurt consumption and HS in the 2011-2016 National Health and Nutrition Examination Survey (NHANES). Probiotic yogurt consumption was assessed using a dietary supplement questionnaire, while HS was evaluated with HS index (HSI). To explore their relationship, weighted univariate regression analysis, subgroup analysis, and interaction analysis were conducted. To evaluate the causal association between yogurt consumption and NAFLD, mendelian randomization analysis (MR) were performed. A restricted cubic spline (RCS) was used to analyze the relationship curve between the leves of yogurt consumption and hepatic steatosis. Results: A total of 7,891 participants were included in the study represented 146.7 million non-institutionalized residents of the United States, of whom 4,322 (54.77%) were diagnosed with HS. Multivariable logistic regression showed probiotic yogurt consumption had significantly inverse relationship for HS (OR = 0.84, 95% CI: 0.72-0.97, p = 0.02) after adjusting for all covariates. Once more, the independent relationship between probiotic yogurt consumption and HS was verified by subgroup analysis and interaction analysis. The MR analysis results indicate that there is no causal relationship between yogurt consumption and NAFLD. The RCS model demonstrated a robust J-shaped link between yogurt consumption and HS, revealing a significant decrease in risk within the lower range of yogurt consumption, which attained the lowest risk close to 0.4 cup. Conclusion: According to the NHANES data, the consumption of probiotics and yogurt has a beneficial effect on HS, whereas the MR results indicated it was not related to NAFLD. The RCS analysis indicates a J-shaped relationship between yogurt consumption and HS, which may account for the inconsistency in the results. Based on these findings, we recommend that adults take half a cup of yogurt daily.

Early Surgery (Within 24 Hours) Benefits Patients Suffering from Acute Thoracolumbar Spinal Cord Injury: A Meta-analysis.

STUDY DESIGN: A meta-analysis of early surgery for acute thoracolumbar spinal cord injury. OBJECTIVE: To evaluate whether early surgery increases the American Spinal Injury Association (ASIA) grade of patients confronted with acute thoracolumbar spinal cord injury. SUMMARY OF BACKGROUND DATA: The idea that early surgery aids the recovery of spinal cord function in patients confronted with acute thoracolumbar spinal cord injury is controversial. METHODS: All articles were retrieved from the PubMed, Embase, Web of Science and Scopus databases, which were searched from onset until 1 May 2021. All data are presented as odds ratios (ORs) and mean deviations (MDs) with 95% confidential intervals (CIs). RESULTS: Ten studies, including 6 prospective studies, 3 retrospective studies, and 1 randomized controlled trial, containing 952 patients, were included in the analysis. The results showed that early surgery significantly reduced the number of patients with ASIA grade A (OR 0.27, 95% CI: 0.13-0.58, P <0.01) and B (OR 0.56, 95% CI: 0.39-0.82, P <0.01) status but greatly increased the number of patients with grade E status (OR 1.44, 95% CI: 1.06-1.96, P <0.01). Generally, the patients receiving early surgery achieved >1 ASIA grade improvement (OR 1.70, 95% CI: 1.31-2.21, P <0.01) or >2 ASIA grade (OR 3.55, 95% CI: 2.20-5.70, P <0.01) improvements. Although early surgery did not reduce the incidence of operative complications (OR 0.72, 95% CI: 0.45-1.16, P <0.01), the duration of hospitalization was greatly shortened (MD-3.48, 95% CI: -0.45 to-2.91, P <0.01). CONCLUSIONS: The spinal cord function of acute thoracolumbar spinal cord injury patients can benefit from early decompression. This conclusion should be further verified with randomized controlled trials.

Therapeutic angiogenesis based on injectable hydrogel for protein delivery in ischemic heart disease.

Ischemic heart disease (IHD) remains the leading cause of death and disability worldwide and leads to myocardial necrosis and negative myocardial remodeling, ultimately leading to heart failure. Current treatments include drug therapy, interventional therapy, and surgery. However, some patients with severe diffuse coronary artery disease, complex coronary artery anatomy, and other reasons are unsuitable for these treatments. Therapeutic angiogenesis stimulates the growth of the original blood vessels by using exogenous growth factors to generate more new blood vessels, which provides a new treatment for IHD. However, direct injection of these growth factors can cause a short half-life and serious side effects owing to systemic spread. Therefore, to overcome this problem, hydrogels have been developed for temporally and spatially controlled delivery of single or multiple growth factors to mimic the process of angiogenesis in vivo. This paper reviews the mechanism of angiogenesis, some important bioactive molecules, and natural and synthetic hydrogels currently being applied for bioactive molecule delivery to treat IHD. Furthermore, the current challenges of therapeutic angiogenesis in IHD and its potential solutions are discussed to facilitate real translation into clinical applications in the future.

What is the optimal dose of adipose-derived mesenchymal stem cells treatment for knee osteoarthritis? A conventional and network meta-analysis of randomized controlled trials.

BACKGROUND: Despite increasing clinical investigations underscoring the efficacy and safety of adipose-derived mesenchymal stem cells (AD-MSCs) therapy in knee osteoarthritis (KOA), no article has recently reviewed the cell dosage. This study aimed to evaluate the efficacy and safety of varying doses of AD-MSCs in treating KOA using conventional and network meta-analysis. METHODS: A search of databases in in Chinese and English was performed to identify randomized controlled trials (RCT) on MSCs for knee osteoarthritis from the inception date to May 1, 2022. This study mainly analyzed the efficacy of AD-MSCs in the treatment of KOA, and subgroup analysis was performed on the therapeutic effects of MSCs from different tissues at the same dose. We divided the different cell doses into low, moderate, and high groups, with the corresponding cell doses: (0-25)*10^6, (25-50)*10^6, and > 50*10^6 cells, respectively. We further analyzed the improvement of improvement of the Visual Analog Scale (VAS) and the Western Ontario and McMaster Universities Arthritis Index (WOMAC) scores and the incidence of adverse events (AEs) after varied dosage injection. RESULTS: A total of 16 literatures were included in this study, of which 8 literatures were about AD-MSCs. Conventional meta-analysis suggests that AD-MSCs can reduce pain and improve function in KOA patients, regardless of the cell doses, up to 12 months of follow-up. The network meta-analysis showed that intra-articular injection of AD-MSCs significantly improved pain and knee function scores in KOA patients compared with the control group at 3, 6, and 12 months. Among the three groups, the high-dose group had the best treatment effect, and the degree of joint pain and dysfunction indicators improved more significantly in the early stage. For adverse events, there was a dose-response trend that increased with increasing doses. CONCLUSIONS: Both cell doses reduced pain and improved knee function in KOA patients. The effect surpassed in the high-dose group than in the moderate-dose, low-dose and control groups. However, adverse events also increase with the increase in dose, which should be carefully considered in clinical application, and the side effects still need to be paid attention to. Considering the limitations of this meta-analysis, future studies need to further explore the efficacy and safety of different doses of treatment, and carry out large sample, multi-center, randomized controlled trials to ensure the reliability and promotion value of the research results.

Deep learning signature based on multiphase enhanced CT for bladder cancer recurrence prediction: a multi-center study.

Background: Accurate stratification of recurrence risk for bladder cancer (BCa) is essential for precise individualized therapy. This study aimed to develop and validate a model for predicting the risk of recurrence in BCa patients postoperatively using 3-phase enhanced CT images. Methods: We retrospectively enrolled 874 BCa patients across four centers between January 2006 and December 2021. Patients from one center were used as training set, while the remaining patients went into the validation set. We trained a deep learning (DL) model based on convolutional neural networks using 3-phase enhanced CT images. The resulting prediction scores were entered into Cox regression analysis to obtain DL scores and construct a DL signature. DL scores and clinical features were then used as deep learning radioclinical signature. The predictive performance of DL signature was assessed according to concordance index and area under curve compared with deep learning radioclinical signature, clinical model and a widely accepted staging grading system. Recurrence-free survival (RFS) and overall survival (OS) were also predicted in order to further assess survival benefits. Findings: DL signature showed strong power for predicting recurrence (concordance index, 0.869; area under curve, 0.889) in validation set, outperforming other models and system. In addition, we divided RFS and OS into high and low risk groups by selecting appropriate cutoff values for DL signature, and calculated cumulative recurrence risk rates for both groups. Interpretation: Our proposed DL signature shows promising potential as clinical aid for predicting postoperative recurrence risk in BCa and for stratifying the risk of RFS and OS, which can be applied to guide personalized precision therapy. Funding: There are no sources of funding for this manuscript.

Identification and experimental validation of autophagy-related genes in abdominal aortic aneurysm.

AIM: Autophagy plays essential roles in abdominal aortic aneurysm (AAA) development and progression. The objective of this study was to verify the autophagy-related genes (ARGs) underlying AAA empirically and using bioinformatics analysis. METHODS: Two gene expression profile datasets GSE98278 and GSE57691 were downloaded from the Gene Expression Omnibus (GEO) database, and principal component analysis was performed. Following, the R software (version 4.0.0) was employed to analyze potentially differentially expressed genes related with AAA and autophagy. Subsequently, the candidate genes were screened using protein-protein interaction (PPI), gene ontology (GO) enrichment analysis, and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. Finally, quantitative real-time polymerase chain reaction (RT-qPCR) was performed to detect the RNA expression levels of the top five selected abnormal ARGs in clinical samples obtained from the normal and AAA patients. RESULTS: According to the information contained (97 AAA patients and 10 healthy controls) in the two datasets, a total of 44 differentially expressed autophagy-related genes (6 up-regulated genes and 38 down-regulated genes) were screened. GO enrichment analysis of differentially expressed autophagy-related genes (DEARGs) demonstrated that some enrichment items were associated with inflammation, and PPI analysis indicated interaction between these genes. RT-qPCR results presented that the expression levels of IL6, PPARG, SOD1, and MAP1LC3B were in accordance with the bioinformatics prediction results acquired from the mRNA chip. CONCLUSION: Bioinformatics analysis identified 44 potential autophagy-related differentially expressed genes in AAA. Further verification by RT- qPCR presented that IL6, PPARG, SOD1, and MAP1LC3B may affect the development of AAA by regulating autophagy. These findings might help explain the pathogenesis of AAA and be helpful in its diagnosis and treatment.

Advanced MRI to assess hippocampal injury after incomplete cerebral ischemia-reperfusion in rats.

BACKGROUND AND PURPOSE: The purpose of this study was to evaluate advanced MRI findings in the bilateral hippocampus CA1 region of rats with hemorrhagic shock reperfusion (HSR) and their correlation with histopathological results. Additionally, this study aimed to identify effective MRI examination methods and detection indexes for assessing HSR. METHODS: Rats were randomized into the HSR and the Sham groups with 24 rats in each group. MRI examination included diffusion kurtosis imaging (DKI) and 3-dimensional arterial spin labeling (3D-ASL). Apoptosis and pyroptosis were evaluated directly from tissue. RESULTS: In the HSR group, cerebral blood flow (CBF) was significantly lower than that of the Sham group, while radial kurtosis (Kr), axial kurtosis (Ka), and mean kurtosis (MK) were all higher. In the HSR group, fractional anisotropy (FA) at 12 and 24 hours and radial diffusivity, axial diffusivity (Da), and mean diffusivity (MD) at 3 and 6 hours were lower than in the Sham group. MD and Da at 24 hours in the HSR group were significantly higher. The apoptosis rate and pyroptosis rate were also enhanced in the HSR group. CBF, FA, MK, Ka, and Kr values in the early stage were strongly correlated with apoptosis rate and pyroptosis rate. The metrics were obtained from DKI and 3D-ASL. CONCLUSIONS: Advanced MRI metrics from DKI and 3D-ASL, including CBF, FA, Ka, Kr, and MK values, are useful to evaluate abnormal blood perfusion and microstructural changes in the hippocampus CA1 area in the setting of incomplete cerebral ischemia-reperfusion in rats induced by HSR.

Human fetal mesenchymal stem cells secretome promotes scarless diabetic wound healing through heat-shock protein family.

The high mortality rate of patients with diabetic foot ulcers is urging the appearance of an effective biomedical drug. Senescence is one of the major reasons of aging-induced decline in the diabetic wound. Our previous studies have demonstrated the anti-senescence effect of secretomes derived from human fetal mesenchymal stem cells (hfMSC). The present study tends to explore the potential role of hfMSC secretome (HFS) in wound healing through anti-aging. Meanwhile, we try to overcome several obstacles in the clinical application of stem cell secretome. A verticle bioreactor and microcarriers are employed to expand hfMSC and produce the HFS on a large scale. The HFS was then subjected to lyophilization (L-HFS). The PLGA (poly lactic-co-glycolic acid) particles were used to encapsulate and protect L-HFS from degradation in the streptozotocin (STZ)-induced diabetic rat model. Results showed that HFS-PLGA significantly enhanced wound healing by promoting vascularization and inhibiting inflammation in the skin wound bed. We further analyzed the contents of HFS. Isobaric tag for relative and absolute quantitation (ITRAQ) and label-free methods were used to identify peptides in the secretome. Bioinformatics analysis indicated that exosome production-related singling pathways and heat-shock protein family could be used as bio-functional markers and quality control for stem cell secretome production.

Extracellular Vesicles in the Pathogenesis, Treatment, and Diagnosis of Spinal Cord Injury: A Mini-Review.

BACKGROUND: Benefiting from in-depth research into stem cells, extracellular vesicles (EVs), which are byproducts of cells and membrane-wrapped microvesicles (30-120 nm) containing lipids, proteins, and nucleic acids, may cast light on the research and development of therapeutics capable of improving the neurological recovery of spinal cord injury (SCI) animals. However, the mechanistic modes of action for EVs in alleviating the lesion size of SCI remain to be solved, thus presenting a tremendous gap existing in translation from the laboratory to the clinic. OBJECTIVE: The purpose of this minireview was to cover a wide range of basic views on EVs involved in SCI treatment, including the effects of EVs on the pathogenesis, treatment, and diagnosis of spinal cord injury. METHODS: We searched databases (i.e., PubMed, Web of Science, Scopus, Medline, and EMBASE) and acquired all accessible articles published in the English language within five years. Studies reporting laboratory applications of EVs in the treatment of SCI were included and screened to include studies presenting relevant molecular mechanisms. RESULTS: This review first summarized the basic role of EVs in cell communication, cell death, inflammatory cascades, scar formation, neuronal regrowth, and angiogenesis after SCI, thereby providing insights into neuroprotection and consolidated theories for future clinical application of EVs. CONCLUSION: EVs participate in an extremely wide range of cell activities, play a critical role in cell communication centring neurons, and are considered potential therapies and biomarkers for SCI. miRNAs are the most abundant nucleic acids shipped by EVs and effluent cytokines, and they may represent important messengers of EVs and important factors in SCI treatment.

Identification of differentially expressed ferroptosis-related genes in abdominal aortic aneurysm: Bioinformatics analysis.

Purpose: Ferroptosis plays a crucial role in the development and progression of abdominal aortic aneurysm (AAA). The aim of this study was to identify differentially expressed genes associated with ferroptosis in AAA through bioinformatics analysis combined with experimental validation. Materials and methods: Firstly, the mRNA expression profile datasets GSE57691 and GSE47472 from Gene Expression Omnibus database were screened, and principal component analysis was carried out. Next, the R software (version 4.0.0) was used to analyze potentially differentially expressed genes associated with AAA and ferroptosis. Subsequently, protein-protein interaction analysis, gene ontology enrichment analysis, and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis were performed on the selected candidate genes. Finally, quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the expression levels of the first five selected abnormal ferroptosis-related genes in clinical samples obtained from patients with AAA and healthy controls. Results: Based on the information contained in the two datasets, a total of 20 differentially expressed ferroptosis-related genes (three upregulated genes and 17 downregulated genes) were selected. Protein-protein interaction analysis demonstrated interaction between these genes, while gene ontology enrichment analysis of ferroptosis genes with differential expression indicated that some enrichment items were associated with oxidative stress. The qRT-PCR results showed that the expression levels of interleukin-6 (IL-6), peroxiredoxin 1 (PRDX1), and stearoyl-CoA desaturase (SCD) were consistent with the bioinformatics prediction results obtained from the mRNA chip. Conclusion: Bioinformatics analysis identified 20 potential ferroptosis-related differentially expressed genes in AAA. Further verification by qRT-PCR showed that IL-6, PRXD1, and SCD might affect the process of AAA by regulating ferroptosis. Our results might assist in further understanding the pathogenesis of AAA and guiding treatment.

Comparison of Outcomes Between Percutaneous Vertebroplasty and Percutaneous Kyphoplasty for the Treatment of Kümmell's Disease: A Meta-Analysis.

STUDY DESIGN: A meta-analysis. OBJECTIVE: The aim is to compare the efficacy of percutaneous vertebroplasty (PVP) and percutaneous kyphoplasty (PKP) in treating Kümmell's disease (KD) without neurological deficits. SUMMARY OF BACKGROUND DATA: PVP and PKP are routine methods for the treatment of KD without neurological deficits; however, whether PVP or PKP is superior is a matter of debate. MATERIALS AND METHODS: According to the Cochrane Handbook for Systematic Reviews of Interventions, PubMed, Embase, the Cochrane Library, and Web of Knowledge were searched for eligible randomized controlled trials or cohort studies. Two authors independently collected data and assessed the methodologic quality of the included studies. Intraoperative and postoperative clinical outcomes, cement leakage, refracture rate, and the costs during hospitalization were evaluated. RESULTS: Five observational studies comparing 119 PVP and 128 PKP patients were included in qualitative and quantitative reviews. All of the included s studies had evidence of good quality, as assessed by the Newcastle-Ottawa scale. On the basis of meta-analysis the operation time [weighted mean difference: -10.65; 95% confidence interval (95% CI): -11.94 to -9.35; P <0.00001] and hospitalization cost (weighted mean difference: -2.38; 95% CI: -2.87 to -1.89; P <0.00001) were less for PVP, while the cement leakage rate was lower for PKP (odds ratio: 3.03; 95% CI: 1.58-5.82; P <0.001). Together, the data indicated that the differences in cement volume, visual analog scale score, Oswestry disability index score, Cobb angle, anterior vertebral height, and refracture rate were not significantly different. CONCLUSION: The findings of this study suggest that PVP and PKP are safe and effective for the treatment of KD. PVP required less operative time and was more affordable, but PKP was superior given the lower cement leakage rate. Additional high-quality randomized controlled trials designed to support these findings are warranted.