Background: Upper limb dystonia is a frequent complication of Wilson's disease (WD). It can lead to poor quality of life and disability. Currently, no effective treatment for it exists. Therefore, we carried out a clinical trial to determine whether high frequency repetitive transcranial magnetic stimulation (rTMS) on the primary motor cortex alleviates upper limb dystonia in WD patients.Methods: This study was a single-center, double-blind, randomized clinical study, included 60 WD patients with upper limb dystonia from a research base of WD in Hefei, China. Participants were randomly divided into a treatment group (TG) and a control group (CG). The TG received rTMS at 10 Hz, while the CG received sham stimulation for 7 consecutive days. Participants were assessed at baseline, after the seventh treatment session, and at 2 and 4 weeks after the seventh treatment session. The primary outcomes included patients' objective muscle tension and stiffness as measured with the MyotonPRO device. The secondary results were scores on clinical scales assessing muscle spasm and motor symptoms, which included the Modified Ashworth Scale (MAS), Unified Wilson's Disease Rating Scale (UWDRS), Burke Fahn Marsden Scale (BFM), and the Activities of Daily Living (ADL) scale.Results: The analysis revealed that after 10 Hz rTMS, muscle tension (P < 0.01) and stiffness (P < 0.01) as measured by the MyotonPRO device decreased significantly in the TG compared to the CG. Moreover, clinically relevant scale scores, including the MAS (P < 0.01), UWDRS (P < 0.01), BFM (P < 0.01), and ADL (P < 0.01) were also significantly reduced.Conclusion: High-frequency rTMS over the primary motor cortex may be an effective complementary and alternative therapy to alleviating upper limb dystonia in WD patients.Clinical Trial Registration:http://www.chictr.org.cn/, identifier: ChiCTR2100046258.

Tongyan spray was an effective and safe method for post-stroke dysphagia patients.

Disposable paper cups are widely used in daily life and most of them are landfilled or incinerated after use, resulting in a serious ecological hazard and significant waste of resources due to the usage of thin polyethylene (PE) as their inner coating. Hence, converting these common solid domestic wastes into high-value added materials is attractive and meaningful. In this study, transparent cellulose-based films were achieved from old bamboo-based disposable paper cups after pretreatment through using the room ionic liquid 1-allyl-3-methylimidazolium chloride (AmimCl) as solvent. The cellulose-based film with a dense texture demonstrated a relatively nice mechanical and UV-shielding performances, and its tensile strength was as high as 48 MPa, much higher than that of commercial polyethylene (PE, 12 MPa) film. Thus, the resultant cellulose-based film showed a great potential in the packaging field. Besides, the flexible paper plastic composites (PPC) were also fabricated from the rest thin PE coating with the stuck fibers, and it was found that PPC showed excellent mechanical property and hydrophobicity. Consequently, a feasible and eco-friendly process of recycling and reusing waste disposable paper cups was developed to achieve a complete utilization and valorization of waste disposable paper cups.

No abstract

Background: Gan–Dou–Fu–Mu decoction (GDFMD) improves liver fibrosis in experimental and clinical studies including those on toxic mouse model of Wilson disease (Model). However, the mechanisms underlying the effect of GDFMD have not been characterized. Herein, we deciphered the potential therapeutic targets of GDFMD using transcriptome analysis.Methods: We constructed a tx-j Wilson disease (WD) mouse model, and assessed the effect of GDFMD on the liver of model mice by hematoxylin and eosin, Masson, and immunohistochemical staining. Subsequently, we identified differentially expressed genes (DEGs) that were upregulated in the Model (Model vs. control) and those that were downregulated upon GDFMD treatment (compared to the Model) using RNA-sequencing (RNA-Seq). Biological functions and signaling pathways in which the DEGs were involved were determined by gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) pathway analyses. A protein–protein interaction (PPI) network was constructed using the STRING database, and the modules were identified using MCODE plugin with the Cytoscape software. Several genes identified in the RNA-Seq analysis were validated by real-time quantitative PCR.Results: Total of 2124 DEGs were screened through the Model vs. control and Model vs. GDFMD comparisons, and dozens of GO and KEGG pathway terms modulated by GDFMD were identified. Dozens of pathways involved in metabolism (including metabolic processes for organic acids, carboxylic acids, monocarboxylic acids, lipids, fatty acids, cellular lipids, steroids, alcohols, eicosanoids, long-chain fatty acids), immune and inflammatory response (such as complement and coagulation cascades, cytokine–cytokine receptor interaction, inflammatory mediator regulation of TRP channels, antigen processing and presentation, T-cell receptor signaling pathway), liver fibrosis (such as ECM-receptor interactions), and cell death (PI3K-Akt signaling pathway, apoptosis, TGF-beta signaling pathway, etc.) were identified as potential targets of GDFMD in the Model. Some hub genes and four modules were identified in the PPI network. The results of real-time quantitative PCR analysis were consistent with those of RNA-Seq analysis.Conclusions: We performed gene expression profiling of GDFMD-treated WD model mice using RNA-Seq analysis and found the genes, pathways, and processes effected by the treatment. Our study provides a theoretical basis to prevent liver fibrosis resulting from WD using GDFMD.

Background: Mitochondrial membrane protein–associated neurodegeneration (MPAN) mostly arises as an autosomal recessive disease and is caused by variants in the chromosome 19 open reading frame 12 (C19orf12) gene. However, a few C19orf12 monoallelic truncating de novo variants have been reported and segregated as autosomal dominant traits in some cases.Methods: We performed whole-exome sequencing and analyzed genes related to neurodegeneration associated with brain iron accumulation for pathogenic variants. The identified variants were confirmed by Sanger sequencing and tested using in silico tools.Results: The patient had an onset of depression at the age of 22 years, which rapidly progressed to severe dystonia, dementia, and bladder and bowel incontinence. Neuroimaging showed hypointensity in the substantia nigra and the globus pallidum, with additional frontotemporal atrophy. Genetic analysis revealed a single complex de novo variant [c.336_338delinsCACA (p.Trp112CysfsTer40)] in the C19orf12 gene.Conclusion: This study enriches the genetic spectrum and clinical features of C19orf12 variants and provides additional evidence of the variable inheritance pattern of MPAN.

No abstract

Objective: Observational epidemiological studies have shown a link between obesity and sepsis, but any causal relationship is not clear. Our study aimed to explore the correlation and causal relationship between body mass index and sepsis by a two-sample Mendelian randomization (MR).Methods: In large sample genome-wide association studies, single-nucleotide polymorphisms related to body mass index were screened as instrumental variables. Three MR methods, MR-Egger regression, weighted median estimator, and inverse variance-weighted, were used to evaluate the causal relationship between body mass index and sepsis. Odds ratio (OR) and 95% confidence interval (CI) were used as the evaluation index of causality, and sensitivity analyses were conducted to assess pleiotropy and instrument validity.Results: By two-sample MR, the inverse variance weighting method results suggested that increased body mass index was associated with an increased risk of sepsis (odds ratio 1.32; 95% CI 1.21–1.44; p = 1.37 × 10−9) and streptococcal septicemia (OR 1.46; 95% CI 1.11–1.91; p = 0.007), but there was no causal relationship with puerperal sepsis (OR, 1.06; 95% CI, 0.87–1.28; p = 0.577). Sensitivity analysis was consistent with the results, and there was no heterogeneity and level of pleiotropy.Conclusion: Our study supports a causal relationship between body mass index and sepsis. Proper control of body mass index may prevent sepsis.