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Objective: Recent studies have suggested that high levels of β2-microglobulin are linked to cognitive deterioration; however, it is unclear how this connects to spinal cord injury (SCI). This study sought to determine whether there was any association between cognitive decline and serum β2-microglobulin levels in patients with SCI., Methods: A total of 96 patients with SCI and 56 healthy volunteers were enrolled as study participants. At the time of enrollment, specific baseline data including age, gender, triglycerides (TG), low-density lipoprotein (LDL), systolic blood pressure (SBP), diastolic blood pressure (DBP), fasting blood glucose (FBG), smoking, and alcohol use were recorded. Each participant was assessed by a qualified physician using the Montreal cognitive assessment (MoCA) scale. Serum β2-microglobulin levels were measured using an enzyme-linked immunosorbent assay (ELISA) reagent for β2-microglobulin., Results: A total of 152 participants were enrolled, with 56 in the control group and 96 in the SCI group. There were no significant baseline data differences between the two groups ( p > 0.05). The control group had a MoCA score of 27.4 ± 1.1 and the SCI group had a score of 24.3 ± 1.5, with the difference being significant ( p < 0.05). The serum ELISA results revealed that the levels of β2-microglobulin in the SCI group were considerably higher ( p < 0.05) than those in the control group (2.08 ± 0.17 g/mL compared to 1.57 ± 0.11 g/mL). The serum β2-microglobulin level was used to categorize the patients with SCI into four groups. As serum β2-microglobulin levels increased, the MoCA score reduced ( p < 0.05). After adjustment of baseline data, further regression analysis showed that serum β2-microglobulin level remained an independent risk factor for post-SCI cognitive impairment., Conclusions: Patients with SCI had higher serum levels of β2-microglobulin, which may be a biomarker for cognitive decline following SCI., Competing Interests: The authors declare that they have no competing interests., (© 2023 Cui et al.)

Background: Astragalus membranaceus (Huang-qi, AM) and Angelica sinensis (Dang-gui, AS) are common Chinese herbal medicines and have historically been used in spinal cord injury (SCI) therapies. However, the underlying molecular mechanisms of AM&AS remain little understood. The purpose of this research was to explore the bioactive components and the mechanisms of AM&AS in treating SCI according to network pharmacology and the molecular docking approach., Methods: AM&AS active ingredients were first searched from Traditional Chinese Medicine Systems Pharmacology (TCMSP) and Traditional Chinese Medicine Information Database (TCM-ID). Meanwhile, we collected relevant target genes of SCI through the GeneCards database, OMIM database, PharmGkb database, DurgBank database, and TDD database. By utilizing the STRING database, we constructed a network of protein-protein interactions (PPIs). In addition, we used R and STRING to perform GO and KEGG function enrichment analyses. Subsequently, AutoDock Vina was employed for a molecular docking study on the most active ingredients and most targeted molecules to validate the results of the network pharmacology analysis mentioned above., Result: The overall number of AM&AS active compounds identified was 22, while the number of SCI-related targets identified was 159. Then, the 4 key active ingredients were MOL000098 quercetin, MOL000422 kaempferol, MOL000354 isorhamnetin, and MOL000392 formononetin. A total of fourteen core targets were TP53, ESR1, MAPK1, MTC, HIF1A, HSP90AA1, FOS, MAPK14, STAT1, AKT1, EGFR, RELA, CCND1, and RB1. The KEGG enrichment analysis results indicated that lipid and atherosclerosis, PI3K-Akt signaling pathway, human cytomegalovirus infection, fluid shear stress, and atherosclerosis, etc., were enhanced with SCI development. Based on the analyses of docked molecules, four main active compounds had high affinity for the key targets., Conclusions: Altogether, it identified the mechanisms by which AM&AS was used for SCI treatment, namely, active ingredients, targets and signaling pathways. Consequently, further research into AM&AS treating SCI can be conducted on this scientific basis., Competing Interests: No other competing interests are declared by any of the authors., (Copyright © 2022 Shengnan Cao et al.)

Objective: Spinal cord injury (SCI) has become prevalent worldwide in recent years, and its prognosis is poor and the pathological mechanism has not been fully elucidated. Nogo-A is one of the isoforms of the neurite outgrowth inhibitory protein reticulon 4. The purpose of this study was to determine whether Nogo-A could be used as a marker for predicting the prognosis of SCI., Methods: We screened eligible SCI patients and controls based on inclusion and exclusion criteria. We also collected baseline clinical information and peripheral venous blood of the enrolled population. Participants' baseline serum Nogo-A levels were measured by enzyme-linked immunosorbent assay (ELISA). The American Spinal Injury Association (ASIA) scale was used to evaluate the prognosis of SCI patients after 3 months., Results: Baseline clinical information (age; gender; smoking; drinking; SBP, systolic blood pressure; DBP, diastolic blood pressure; fasting blood glucose; WBC, white blood cells; CRP, C-reactive protein) of SCI patients and controls were not statistically significant academic differences ( p > 0.05). The baseline serum Nogo-A levels of SCI patients and controls were 192.7 ± 13.9 ng/ml and 263.1 ± 22.4 ng/ml, respectively, and there was a statistically significant difference between the two groups ( p < 0.05). We divided SCI patients into 4 groups according to their baseline serum Nogo-A quartile levels and analyzed their relationship with ASIA scores. The trend test results showed that with the increase of Nogo-A level, the ASIA sensation score and ASIA motor score were significantly decreased ( p < 0.001). Multivariate regression analysis showed that serum Nogo-A levels remained a potential cause affecting the prognosis of SCI after adjusting for confounding factors in multiple models., Conclusions: Serum Nogo-A levels were significantly elevated in SCI patients. Moreover, elevated Nogo-A levels often indicate poor prognosis and can be used as a marker to predict the prognosis of SCI., Competing Interests: The authors report no conflict of interest., (Copyright © 2022 Haojun Shi et al.)

Background: Spinal cord injury (SCI) has high incidence globally and is frequently accompanied by subsequent cognitive decline. Accurate early risk-categorization of SCI patients for cognitive decline using biomarkers can enable the timely application of appropriate neuroprotective measures and the development of new agents for the management of SCI-associated cognitive decline. Neuropeptide FF is an endogenous neuropeptide with a multitude of functions and is associated with neuroinflammatory processes. This prospective study investigated the predictive value of serum neuropeptide FF levels measured after acute SCI for subsequent cognitive decline., Methods: 88 patients presenting with acute SCI without preexisting neurological injury, brain trauma, or severe systemic illness and 60 healthy controls were recruited. Serum neuropeptide FF levels, clinical, and routine laboratory variables including low-density lipoprotein, high-density lipoprotein, fasting blood glucose, total triiodothyronine (TT3), total thyroxine (TT4), and thyroid-stimulating hormone (TSH) levels collected from all subjects were assessed. Montreal cognitive assessment (MoCA) was performed 3 months after enrollment. SCI patients were grouped according to quartile of serum neuropeptide FF level and MoCA scores were compared using ANOVA. Additionally, multivariate linear regression with clinical and laboratory variables was performed to predict MoCA scores., Results: SCI patients displayed significantly higher baseline serum neuropeptide FF levels than healthy controls (38.5 ± 4.1 versus 23.4 ± 2.0 pg/ml, p < 0.001 ∗∗ ). SCI patients in higher quartiles of baseline serum neuropeptide FF displayed significantly lower MoCA scores at 3 months. Linear regression analysis indicated serum neuropeptide FF levels as a significant independent predictor of worse MoCA scores after SCI ( r = 0.331, p = 0.034 ∗ )., Conclusion: Early serum neuropeptide FF levels significantly and independently predicted cognitive decline after acute SCI among patients without preexisting neurological disorders., Competing Interests: The authors report no conflict of interest., (Copyright © 2021 Shifei Sun et al.)

Objective: Leucine-rich α 2 glycoprotein 1 (LRG1) is a novel cytokine, which is believed to be involved in the inflammatory process of a series of diseases. However, the relationship between LRG1 and spinal cord injury (SCI) has not been reported. The purpose of our study is to determine the predictive value of LRG1 for the prognosis of pediatric SCI (PSCI)., Methods: This study recruited 64 patients with confirmed PSCI and 40 healthy controls at Foshan Traditional Chinese Medicine Hospital from January 2016 to December 2020. The clinical information of all participants at the time of admission was recorded. Peripheral blood was collected, and commercial reagents were used to detect the level of serum LRG1. At the same time, the International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI) was used to assess the severity of PSCI., Results: All participants were divided into PSCI group ( n = 64) and NC group ( n = 40). There was no significant difference in clinical information (age, gender, heart rate, systolic blood pressure, diastolic blood pressure, sampling time from injury, white blood cells, and C-reactive protein) between the two groups ( p > 0.05). According to the interquartile range of serum LRG1, we compared the motor and sensory scores of ISNCSCI and found that serum LRG1 levels were negatively correlated with the prognosis of PSCI patients ( p < 0.001). The results of receiver operating curve (ROC) showed that the sensitivity, specificity, and AUC (Area Under the Curve) of serum LRG1 level in predicting the prognosis of PSCI were 68.4%, 69.1%, and 0.705, respectively. The cut-off value of serum LRG1 level predicting the prognosis of PSCI is 21.1  μ g/ml., Conclusions: Serum LRG1 level is significantly increased in PSCI patients, and the elevated LRG1 level is negatively correlated with the prognosis of PSCI patients. Serum LRG1 may be a potentially useful biomarker for predicting PSCI., Competing Interests: All the authors declare no conflict of interests., (Copyright © 2021 Hong Ma et al.)

Objective: Interleukin-37 (IL-37) is a new cytokine that naturally inhibits inflammation. Inflammation plays an important role in acute spinal cord injury (SCI). The purpose of this study is to check whether serum IL-37 can be used as a clinical predictor of SCI., Methods: All subjects underwent venipuncture within 24 hours of enrollment to obtain peripheral blood and then centrifuged to obtain serum. The concentration of serum IL-37 was determined by enzyme-linked immunosorbent assay (ELISA). One month after the injury, the American Spinal Cord Injury Association (ASIA) impairment scale was used for neurological examination., Results: A total of 148 people were included in the study, including 52 normal controls (NC) and 96 patients with acute SCI within 24 hours of onset. The comparison of clinical baseline data (age, gender, BMI: body mass index, smoking, alcohol drinking, CHD: coronary heart disease, HBP: high blood pressure, and DM: diabetes mellitus) between the two groups was not statistically significant ( p > 0.05). However, the serum IL-37 concentration of SCI patients was significantly higher than that of the NC group, and the difference was statistically significant ( p < 0.001). And with the aggravation of SCI grade, the level of IL-37 increased significantly ( p < 0.05). Pearson correlation analysis further showed that serum IL-37 concentration is negatively correlated with AISA motor score ( r = -0.327, p < 0.05)., Conclusion: The serum IL-37 concentration of SCI patients is significantly increased, and it is closely related to the recovery of motor function. We proved for the first time that serum IL-37 has prognostic value in patients with SCI. In addition, serum IL-37 may be used as a prognostic biomarker for SCI., Competing Interests: All the authors declare no conflict of interests., (Copyright © 2020 Yuanzhen Chen et al.)

Objective: Cognitive impairment is considered to be an important complication of spinal cord injury (SCI), but its underlying mechanism remains unclear. The purpose of this study is to explore whether serum CCL21 can be used as a potential biomarker of cognitive impairment in SCI., Methods: In Neck-Shoulder and Lumbocrural Pain Hospital, Shandong First Medical University & Shandong Academy of Medical Sciences, hospitalized or treated acute SCI patients were included in the study as the SCI group (SCI). At the same time, a normal control group (NC) matching the age and sex of the SCI group was recruited in the outpatient clinic. Once the two groups were enrolled, their demographics and clinical characteristics were collected immediately. Enzyme-linked immunosorbent assay (ELISA) was used to detect serum CCL21 levels within 24 hours of admission. Three months later, the Montreal Cognitive Assessment (MoCA) was used to test the cognitive function of the population., Results: A total of 84 SCI patients and 49 NC populations were eligible for inclusion in the study. There was no significant statistical difference in the demographics and clinical characteristics (age, gender, BMI, TG, LDL-C, FBG, SBP, and DBP) between the two groups ( p > 0.05). Compared with the NC group, the SCI group had a higher serum CCL21 level ( p < 0.001) and a lower MoCA score ( p < 0.001). Serum CCL21 level in SCI was negatively correlated with MoCA score ( p = 0.023). Multivariable analyses showed that serum CCL21 level is an independent prognostic factor of cognitive impairment in SCI., Conclusions: MoCA score has a linear relationship with serum CCL21 quartile, and SCI cognitive function has a negative correlation with serum CCL21. Serum CCL21 is an independent risk factor for cognitive impairment after SCI., Competing Interests: All the authors declare no conflict of interests., (Copyright © 2020 Yuanzhen Chen et al.)

Objective. Leucine-rich α2 glycoprotein 1 (LRG1) is a novel cytokine, which is believed to be involved in the inflammatory process of a series of diseases. However, the relationship between LRG1 and spinal cord injury (SCI) has not been reported. The purpose of our study is to determine the predictive value of LRG1 for the prognosis of pediatric SCI (PSCI). Methods. This study recruited 64 patients with confirmed PSCI and 40 healthy controls at Foshan Traditional Chinese Medicine Hospital from January 2016 to December 2020. The clinical information of all participants at the time of admission was recorded. Peripheral blood was collected, and commercial reagents were used to detect the level of serum LRG1. At the same time, the International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI) was used to assess the severity of PSCI. Results. All participants were divided into PSCI group (n = 64) and NC group (n = 40). There was no significant difference in clinical information (age, gender, heart rate, systolic blood pressure, diastolic blood pressure, sampling time from injury, white blood cells, and C-reactive protein) between the two groups (p > 0.05). According to the interquartile range of serum LRG1, we compared the motor and sensory scores of ISNCSCI and found that serum LRG1 levels were negatively correlated with the prognosis of PSCI patients (p < 0.001). The results of receiver operating curve (ROC) showed that the sensitivity, specificity, and AUC (Area Under the Curve) of serum LRG1 level in predicting the prognosis of PSCI were 68.4%, 69.1%, and 0.705, respectively. The cut-off value of serum LRG1 level predicting the prognosis of PSCI is 21.1 μg/ml. Conclusions. Serum LRG1 level is significantly increased in PSCI patients, and the elevated LRG1 level is negatively correlated with the prognosis of PSCI patients. Serum LRG1 may be a potentially useful biomarker for predicting PSCI. [ABSTRACT FROM AUTHOR]