The aim of the study was to assess a panel of promising biomarkers for their ability to improve diagnosis of sporadic amyotrophic lateral sclerosis (ALS). Forty patients with sporadic ALS and 40 controls with other neurological diseases were evaluated. Levels of phosphorylated neurofilament heavy chain (pNfH), S100-β, cystatin C, and chitotriosidase (CHIT) in cerebrospinal fluid were assayed using two-site solid-phase sandwich ELISA. Patients with sporadic ALS showed higher levels of pNfH and CHIT than controls, but lower levels of cystatin C. Multivariate logistic regression that adjusted for patient age and sex identified significant associations between sporadic ALS and levels of pNfH, CHIT and cystatin C. Levels of pNfH correlated positively with rate of progression and decline based on the Amyotrophic Lateral Sclerosis Functional Rating Scale - Revised. Based on receiver operating curve analysis, a pNfH cut-off of 437 ng/L discriminated patients from controls with a sensitivity of 97.3 % and specificity of 83.8 %. A CHIT cut-off of 1593.779 ng/L discriminated patients from controls with a sensitivity of 83.8 % and specificity of 81.1 %. Combining the two biomarkers gave a sensitivity of 83.8 % and specificity of 91.9 %. Levels of pNfH in cerebrospinal fluid may be a reliable biomarker for diagnosing ALS, and combining this biomarker with levels of CHIT may improve diagnostic accuracy.

Background: Cystatin C (CysC) levels in amyotrophic lateral sclerosis (ALS) have been found changes, however, the associations between serum CysC levels and the progression and survival of ALS remain largely unknown.Methods: A total of 1,086 ALS patients and 1,026 sex-age matched healthy controls (HCs) were enrolled in this study. Serum CysC, other renal function, and metabolic parameters were measured. Correlation analysis and binary logistic regression were used to explore the factors related to serum CysC. Kaplan–Meier curve and Cox regression model were used for survival analysis.Results: CysC levels were significantly higher in ALS patients compared to HCs (0.94 vs. 0.85 mg/L, p < 0.001). Compared with ALS patients with lower CysC levels, those with higher CysC levels had an older age of onset, significantly lower ALSFRS-R scores (40.1 vs. 41.3, p < 0.001), a faster disease progression rate (0.75 vs. 0.67, p = 0.011), and lower frontal lobe function scores (15.8 vs. 16.1, p = 0.020). In the correlation analysis, CysC levels were significantly negatively correlated with ALSFRS-R scores (r = −0.16, p < 0.001). Additionally, ALS patients with higher CysC levels had significantly shorter survival time (40.0 vs. 51.8, p < 0.001) compared to patients with lower CysC levels. Higher CysC levels were associated with a higher risk of death in Cox analysis (HR: 1.204, 95% CI: 1.012–1.433). However, when treatment was included in the model, the result was no longer significant.Conclusion: CysC levels in ALS patients were higher compared to HCs. Higher CysC levels were associated with greater disease severity, faster progression rate and shorter survival, needing early intervention.

This paper examines how Guo Xiang's view on the virtues of legendary sage-kings such as the Yellow Emperor, Yao, Shun, and Yu differs from their depiction in the Zhuangzi, based on his commentary on the text and with cross-references to his fragmentary commentary to the Analects. Despite the varying virtues of the sage-kings and their criticisms in the Zhuangzi, Guo Xiang reconciled them and argued that not only were they equally praiseworthy, they were indeed no different at all. To him, the criticisms of the sage-kings in the Zhuangzi only targeted at the traces of their sagely virtue rather than the sagely virtue itself. The virtues of the sage-kings, according to the Zhuangzi, caused more harm than good, whereas Guo Xiang argued that a sageless epoch was undesirable. The paper will conclude with Guo Xiang's political insights on the cause of the harmful impact of virtue's degeneration and chaos in the world.

Objectives. Recently, biallelic variants in MED27 have been identified to correlate with complex dystonia. However, no replicative study has been conducted in larger dystonia cohorts. In this study, we aimed to systematically evaluate the genetic associations of MED27 with dystonia in a large dystonia cohort. Materials and Methods. We analyzed rare variants (minor allele ) of MED27 in a large Chinese dystonia cohort with whole exome sequencing. The overrepresentation of rare variants in patients was examined with Fisher’s exact test at allele and gene levels. Results. A total of 688 patients with dystonia were included in the study, including 483 isolated dystonia, 133 combined dystonia, and 72 complex dystonia. The average age at onset (SD) was 34.3 (19.1) years old. After applying filtering criteria, five rare variants, namely, p.R247H, p.P174A, p.P123A, p.L120F, and p.F56C, were identified in six individuals. All of them carried the variant in the heterozygous form, and no patients with compound heterozygous or homozygous alleles were identified. At allele level, no variant was associated with risk of dystonia. Gene-based burden analysis did not detect enrichment of rare variants of MED27 in dystonia either. Conclusion. Variants of MED27 were rare in Chinese dystonia patients, probably because that mutations in MED27 are more associated with more complex neurodevelopmental disorders that can also include dystonia among the various neurological features. Further studies are needed to confirm the role of MED27 in dystonia and other neurological disorders.