Cognition and pain share common neural substrates and interact reciprocally: chronic pain compromises cognitive performance, whereas cognitive processes modulate pain perception. In the present study, we established a non-drug-dependent rat model of context-based analgesia, where two different contexts (dark and bright) were matched with a high (52°C) or low (48°C) temperature in the hot-plate test during training. Before and after training, we set the temperature to the high level in both contexts. Rats showed longer paw licking latencies in trials with the context originally matched to a low temperature than those to a high temperature, indicating successful establishment of a context-based analgesic effect in rats. This effect was blocked by intraperitoneal injection of naloxone (an opioid receptor antagonist) before the probe. The context-based analgesic effect also disappeared after optogenetic activation or inhibition of the bilateral infralimbic or prelimbic sub-region of the prefrontal cortex. In brief, we established a context-based, non-drug dependent, placebo-like analgesia model in the rat. This model provides a new and useful tool for investigating the cognitive modulation of pain.

BackgroundPLA2G6-associated neurodegeneration (PLAN) is a heterogeneous group of neurodegenerative diseases caused by biallelic PLA2G6 mutations, covering diseases such as infantile neuroaxonal dystrophy (INAD), atypical neuroaxonal dystrophy (ANAD), dystonia parkinsonism (DP), and autosomal recessive early-onset parkinsonism (AREP). The study aims to report the clinical and genetic features of a series of PLAN patients.MethodsThe clinical and radiological findings of five Chinese patients from three families were collected. Whole-exome next generation sequencing (NGS) was applied to identify the genetic causes. Co-segregation analysis of the detected candidate variants were performed in their families. The pathogenicity of identified novel variants was predicted by in silico analysis.ResultsNGS revealed compound heterozygous variants of PLA2G6 gene in all five patients. There were six PLA2G6 variants identified, including two known variants (c.116G>A, c.238G>A) and four novel variants (c.2120dupA, c.2071C>G, c.967G>A, c1534T>A). ACMG predicts c.2120dupA to be pathogenic, c.2071C>G and c.1534T>A to be likely pathogenic, and c1534T>A to be of uncertain significance. Clinically, four patients fell into the diagnosis of ANAD, and 1 into the diagnosis of AREP. Brain imaging revealed cerebellar atrophy, iron deposition in bilateral globus pallidus, and substantia nigra in three cases.ConclusionsFour novel pathogenic variants were discovered and the pathogenic variant spectrum of the PLA2G6 gene was expanded.

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Objective: The objective of this research was to study the clinical features, genetic characteristics, muscle imaging, and muscle pathological changes of a cohort of Chinese patients with mutations in the valosin-containing protein (VCP) gene. Methods: Nine patients from seven Chinese pedigrees were recruited. Variants were detected by next-generation sequencing and confirmed by Sanger sequencing. Thigh muscle MRIs were performed in five patients. All the patients received muscle biopsies.Results: Seven variants in VCP were identified, and two were novel. All the patients presented with adult-onset muscle weakness. The appearance of "isolated island sign" or "contra-isolated island sign" was observed in four of the five the patients on muscle MRIs. Muscle biopsies demonstrated the combination of neuropathic and myopathic changes in seven patients and muscle dystrophic changes in two patients. Notably, rimmed vacuoles and cytoplasmic VCP and p62-positive protein aggregates were observed in all the patients. Conclusion:Our finding of novel variants expanded the mutational spectrum of the VCP gene. This cohort of Chinese patients with VCP mutations mainly present with inclusion body myopathy with predominant limb-girdle distribution.The characteristic pattern of fatty infiltration, especially the "isolated island" and "contra-isolated island" on muscle MRI, along with rimmed vacuoles in muscle biopsy, provides valuable clues for guiding genetic diagnostic workup.

As a well-known dairy company in China, Yili officially completed the acquisition of infant formula goat milk powder head company Ausnutria Dairy in 2022. This acquisition has become the largest merger in the dairy industry in recent years. This paper analyzes the motivation and integration process of Yili’s merger and acquisition of Ausnutria Dairy, and uses event research method and accounting research method to measure the market performance and financial performance of the merger and acquisition, and on this basis, the effect of the merger and acquisition is systematically evaluated. The study found that after the merger, the market responded positively, shareholder wealth increased, and mergers and acquisitions had a positive impact on profitability, growth ability and solvency in addition to a slight reduction in Yili’s operating capacity. Finally, the research puts forward the enlightenment of enterprise merger and acquisition, and provides experience for enterprise horizontal merger and acquisition.