Objective To investigate the pharmacological effects of"Yajieshaba"on mice with alcohol-induced liver injury and to investigate the mechanism of the impact of"Yajieshaba"on the regulation of intestinal flora by 16S rDNA technology.Methods Healthy male KM mice were randomly divided into control,model,"Yajieshaba"low,medium,and high dose(0.39,1.17 and 3.51 g·kg-1)groups and Bifendatatum(2.93 mg·kg-1)groups,with eight mice in each group.After one week of pre-administration of"Yajieshaba",a mouse model of acute alcoholic liver injury was established by a single instillation of 56%alcohol,and the levels of AST and ALT in the serum of mice were measured,and the morphological changes of liver histology were observed by HE staining;secondly,faecal DNA was extracted from each group under aseptic operation,and 16S rDNA sequencing and differential analysis by alpha diversity and species composition at the phylum and genus levels were performed.Results The results showed that the biochemical indexes of liver function(ALT and AST)were significantly improved by"Yajieshaba",and the degree of liver damage was significantly reduced by HE staining.At the phylum level,it significantly decreased the abundance of Aspergillus and increased the quantity of Bacteroides;at the genus level,it significantly up-regulated the plenty of Bacteroides and Prevotella and downregulated a lot of Prevotella and Helicobacter.At the genus level,"Yajieshaba"significantly up-regulated the abundance of Bacillus spp.and Prevotella spp.and down-regulated the abundance of Prevotella spp.and Helicobacter spp.Conclusion"Yajieshaba"may play an anti-acute alcoholic liver injury effect by regulating the intestinal flora and metabolites.

Anhedonia is defined as the reduction of pleasure and reward-seeking behavior,and it is prevalent in approximately two-thirds of individuals diagnosed with post-traumatic stress disorder(PTSD).Numerous empirical studies have consistently demonstrated that anhedonia represents an independent symptom dimension of PTSD.Furthermore,additional investigations have revealed that anhedonia plays a crucial role in the psychopathology of PTSD,contributing to the maintenance of post-traumatic stress responses,as well as more severe functional impairment and reduced therapeutic responsiveness.This paper aims to discuss the definition,psychopathology,genetic mechanisms and neurobiological underpinnings of anhedonia in PTSD,thus providing insights for future research on anhedonic symptoms.

The neurotrophin-tyrosine receptor kinase B (TrkB) signaling pathway plays an important role in regulating the balance of excitation and inhibition in the primary visual cortex (V1). Previous studies have revealed its mechanism of regulating the level of cortical excitability by increasing the efficiency of excitatory transmission, but it has not been elucidated how TrkB receptors regulate the balance of excitation and inhibition through the inhibitory system, which in turn affects visual cortex function. Therefore, the objective of this study was to investigate how the TrkB signaling pathway specifically regulates the most important inhibitory neuron-PV neurons affects the visual cortex function of mice. The expression of TrkB receptor on PV neurons in the V1 region was specifically reduced by the virus, the functional changes of inhibitory and excitatory neurons in the primary visual cortex were recorded by multi-channel electrophysiological in vivo. The orientation discrimination ability of mice was tested by behavioral experiments, and altered orientation discrimination ability of mice was tested by behavioral experiments. The results showed that reduced expression of TrkB receptors on PV inhibitory neurons in primary visual cortex significantly increased the response intensity of excitatory neurons, reduced the orientation discrimination ability of inhibitory and excitatory neurons, and increased the signal-to-noise ratio, but the orientation discrimination ability at the individual level in mice showed a decrease. These results suggest that the TrkB signaling pathway does not modulate the function of PV neurons solely by increasing excitatory transmission targeting PV neurons, and its effect on neuronal signal-to-noise ratio is not due to enhancement of the inhibitory system.
Mice ; Animals ; Receptor, trkB/metabolism* ; Neurons/metabolism* ; Signal Transduction

With the improved understanding of driver mutations in non-small cell lung cancer (NSCLC), expanding the targeted therapeutic options improved the survival and safety. However, responses to these agents are commonly temporary and incomplete. Moreover, even patients with the same oncogenic driver gene can respond diversely to the same agent. Furthermore, the therapeutic role of immune-checkpoint inhibitors (ICIs) in oncogene-driven NSCLC remains unclear. Therefore, this review aimed to classify the management of NSCLC with driver mutations based on the gene subtype, concomitant mutation, and dynamic alternation. Then, we provide an overview of the resistant mechanism of target therapy occurring in targeted alternations ("target-dependent resistance") and in the parallel and downstream pathways ("target-independent resistance"). Thirdly, we discuss the effectiveness of ICIs for NSCLC with driver mutations and the combined therapeutic approaches that might reverse the immunosuppressive tumor immune microenvironment. Finally, we listed the emerging treatment strategies for the new oncogenic alternations, and proposed the perspective of NSCLC with driver mutations. This review will guide clinicians to design tailored treatments for NSCLC with driver mutations.
Humans ; Carcinoma, Non-Small-Cell Lung/genetics* ; Lung Neoplasms/genetics* ; Mutation ; Tumor Microenvironment/genetics*