Contra-Directional Expression of Serum Homocysteine and Uric Acid as Important Biomarkers of Multiple System Atrophy Severity: A Cross-Sectional Study

Aims. There is evidence suggesting that inflammatory responses play a critical role in the pathogenesis of multiple system atrophy (MSA). Whether inflammatory mediators can be used as reliable biomarkers to detect the severity and progression of MSA remains largely unknown. Methods. We performed a cross-sectional study that included 47 patients with MSA and 50 healthy age-matched controls. Serum levels of homocysteine (Hcy), uric acid (UA) and C-reactive protein (CRP) were measured. These levels positively correlated with the severity of MSA, based on both motor and non-motor symptoms (NMS). Several scales were used to rate the severity of MSA, including the Unified multiple system atrophy rating scale (UMSARS), Parkinson’s disease sleep scale (PDSS), Non-motor Symptoms Scale (NMSS), the Schwab & England Activities of Daily Living Scale (ADL), Webster Scale, modified Hoehn and Yahr staging scale (H&Y), and the Mini-Mental State Examination (MMSE). Receiver Operating Characteristic (ROC) curves was applied to map the diagnostic accuracy of MSA against healthy subjects. Results. Compared with healthy subjects, we found that serum Hcy was higher, UA was lower, and CRP levels were unchanged in MSA patients. These findings were especially prominent in male patients. No significant differences of serum Hcy and UA were observed between patients of MSA and PD. Interestingly, there was a significant correlation between Hcy levels and MSA severity such as movement dysfunction, declined cognition, and cardiovascular symptoms. Additionally, the ROC curve for the combination of Hcy and UA (AUC 0.736) showed potential diagnostic value in discriminating MSA from healthy subjects. Conclusions. Our findings suggest that the inflammatory mediators Hcy and UA may play important roles in the pathogenesis of MSA. The measurement of serum Hcy and UA levels could then be a useful tool to accurately distinguish MSA from healthy subjects

Elevation of YKL-40 in the CSF of Anti-NMDAR Encephalitis Patients Is Associated With Poor Prognosis

Objective: Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis predominantly affects children and young women; the disease can have a multistage presentation and exhibit a wide variety of neuropsychiatric features. This study aimed to investigate the profile of YKL-40 (Chitinase 3-like 1) in anti-NMDAR encephalitis patients and evaluate its association with modified Rankin Scale (mRS) scores and expression of inflammatory cytokines.Methods: A total of 66 patients were enrolled in this study, 33 with anti-NMDAR encephalitis, 13 with viral meningitis and 20 with non-inflammatory neurological disease. Patients were evaluated to determine mRS scores at disease onset and at the 3 month follow-up; cerebrospinal fluid (CSF) samples were collected in the meantime. CSF levels of YKL-40 and cytokines (TNF-α, IL-6, IL-10) were measured by enzyme-linked immunosorbent assay.Results: CSF levels of YKL-40 and inflammatory cytokines (TNF-α, IL-6, IL-10) were all more highly elevated in patients with anti-NMDAR encephalitis at the acute stage of disease compared with the controls. Levels of CSF YKL-40 were correlated with levels of IL-6 both at disease onset and at the 3 month follow-up. Changes in YKL-40 levels were significantly correlated with improved mRS scores in patients with anti-NMDAR encephalitis.Conclusion: Our study suggests that CSF levels of YKL-40 in patients with anti-NMDAR encephalitis were increased and correlated with clinical mRS scores. This may be reflective of the underlying neuroinflammatory process. YKL-40 demonstrates potential as a possible biomarker for the prognosis of anti-NMDAR encephalitis

Higher CSF Levels of NLRP3 Inflammasome Is Associated With Poor Prognosis of Anti-N-methyl-D-Aspartate Receptor Encephalitis

Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is accepted as an autoimmune disorder of the central nervous system (CNS). NLR family pyrin domain containing 3 (NLRP3) inflammasome, a potent innate inflammatory mediator, can activate IL-1β and induce the migration of T helper cell into CNS. However, the possible role of NLRP3 inflammasome in the pathogenesis of anti-NMDAR encephalitis remains unclear. This study aims to determine the levels of NLRP3 and related cytokines (IL-1β, IL-6, and IL-17) in the cerebrospinal fluid (CSF) of anti-NMDAR encephalitis patients and to assess whether NLRP3 influences the clinical outcomes of this disease. Twenty-five patients with anti-NMDAR encephalitis, 12 viral meningoencephalitis patients and 26 controls with non-inflammatory neurological diseases were recruited. CSF NLRP3 inflammasome, IL-1β, IL-6, and IL-17 were measured by enzyme-linked immunosorbent assay. Thirteen out of 25 patients were re-examed for the concentrations of NLRP3 and cytokines 6 months later. Our results showed significant increases of CSF NLRP3 inflammasome, IL-1β, IL-6, and IL-17 in anti-NMDAR encephalitis patients. There were positive correlations between CSF NLRP3 inflammasome and cytokines in anti-NMDAR encephalitis patients. There was also a positive correlation between maximum modified Rankin Scale (mRS) scores and CSF NLRP3 inflammasome in anti-NMDAR encephalitis patients. During follow-up, the decrease of mRS was positively correlated with the decrease of CSF NLRP3 inflammasomes. These results suggested that the level of CSF NLRP3 inflammasome could represent the severity of anti-NMDAR encephalitis and the reduction of CSF NLRP3 inflammasome could act as an indicator for the prognosis of this disease

Theoretical Study on the Potential Existing Forms and Microwave Rotational Spectrum of Short-Chain Fatty Acids in Interstellar Space

Several short-chain fatty acids and their corresponding potential existing hydrated forms are important molecules in interstellar space. Their structures were optimized with twelve different computational methods. The dipole moments and the spectral constants, including rotational constants and centrifugal distortion constants were obtained. According to the benchmark study, revDSD-PBEP86-D3(BJ) is the most suitable method that was selected for rotational calculation. Symmetry-adapted perturbation theory was used to study the strength and composition of the interaction between acids and water in clusters. The possibility of its existing under the low-temperature and low-pressure conditions was confirmed by calculating of binding free energy. Furthermore, ab initio molecular dynamics simulations were used to investigate whether the internal rotations of acids could be observed. The 3-fold splitting from the predicted high-resolution microwave rotational spectra of the acetic acid monohydrate at different temperatures perfectly proved the accuracy of the simulations

Predictive value of the systemic immune inflammation (SII) index for stroke‐associated pneumonia

Abstract Objective To investigate the predictive value of the systemic immune inflammation (SII) index on the occurrence of stroke‐associated pneumonia (SAP) in patients with acute stroke. Methods Data of patients with or without a previous history of pulmonary who visited the First Affiliated Hospital of Kunming Medical University within 24 h of the onset of stroke were collected between January 2017 and December 2019. Patient's demographic data, stroke type, past medical history, National Institutes of Health Stroke Scale score, Glasgow Coma score, and laboratory tests were collected. Logistic regression models and receiver‐operating characteristic (ROC) curves were used to investigate the predictive value of SII for the development of SAP in patients with stroke. Results We included 395 patients with acute stroke, with a mean age of 63.89 ± 13.42 years, of whom 340 (86.1%) had ischemic stroke, and 55 (13.9%) had hemorrhagic stroke. Out of 395, 113 (28.6%) had SAP and 282 (71.4%) did not, and the SII level in the SAP group was higher than that of the non‐SAP group (p < .05). Logistic regression analysis of patients with stroke showed that higher SII was a risk factor for SAP in patients with stroke (per 100 units, HR = 1.081, 95% CI: 1.035–1.130, p < .001), and tertile grouping of SII showed that the risk of SAP was 5.059 times higher in the SIIQ3 group than in the SIIQ1 group (95% CI: 2.061–12.418, p < .001). ROC curve analysis indicated that the SII index had predictive value for the occurrence of SAP in patients with stroke, with an area under the curve of 0.752 (95% CI: 0.698–0.806). When the cutoff value was 861.01, the SII predicted SAP in patients with stroke with a sensitivity of 61.9% and a specificity of 76.2%. Conclusion Higher SII is an independent risk factor for the development of SAP in patients with stroke and has some predictive value for the development of SAP