ObjectiveMagnetoencephalography (MEG), a non-invasive neuroimaging technique, meticulously captures the magnetic fields emanating from brain electrical activity. Compared with MEG based on superconducting quantum interference devices (SQUID), MEG based on optically pump magnetometer (OPM) has the advantages of higher sensitivity, better spatial resolution and lower cost. However, most of the current studies are clinical studies, and there is a lack of animal studies on MEG based on OPM technology. Pain, a multifaceted sensory and emotional phenomenon, induces intricate alterations in brain activity, exhibiting notable sex differences. Despite clinical revelations of pain-related neuronal activity through MEG, specific properties remain elusive, and comprehensive laboratory studies on pain-associated brain activity alterations are lacking. The aim of this study was to investigate the effects of inflammatory pain (induced by Complete Freund’s Adjuvant (CFA)) on brain activity in a rat model using the MEG technique, to analysis changes in brain activity during pain perception, and to explore sex differences in pain-related MEG signaling. MethodsThis study utilized adult male and female Sprague-Dawley rats. Inflammatory pain was induced via intraplantar injection of CFA (100 μl, 50% in saline) in the left hind paw, with control groups receiving saline. Pain behavior was assessed using von Frey filaments at baseline and 1 h post-injection. For MEG recording, anesthetized rats had an OPM positioned on their head within a magnetic shield, undergoing two 15-minute sessions: a 5-minute baseline followed by a 10-minute mechanical stimulation phase. Data analysis included artifact removal and time-frequency analysis of spontaneous brain activity using accumulated spectrograms, generating spectrograms focused on the 4-30 Hz frequency range. ResultsMEG recordings in anesthetized rats during resting states and hind paw mechanical stimulation were compared, before and after saline/CFA injections. Mechanical stimulation elevated alpha activity in both male and female rats pre- and post-saline/CFA injections. Saline/CFA injections augmented average power in both sexes compared to pre-injection states. Remarkably, female rats exhibited higher average spectral power 1 h after CFA injection than after saline injection during resting states. Furthermore, despite comparable pain thresholds measured by classical pain behavioral tests post-CFA treatment, female rats displayed higher average power than males in the resting state after CFA injection. ConclusionThese results imply an enhanced perception of inflammatory pain in female rats compared to their male counterparts. Our study exhibits sex differences in alpha activities following CFA injection, highlighting heightened brain alpha activity in female rats during acute inflammatory pain in the resting state. Our study provides a method for OPM-based MEG recordings to be used to study brain activity in anaesthetized animals. In addition, the findings of this study contribute to a deeper understanding of pain-related neural activity and pain sex differences.

OBJECTIVE To investigate the potential mechanism of Sanqi danshen tablets in the treatment of non-alcoholic fatty liver disease （NAFLD）. METHODS Core targets of Sanqi danshen tablets in the treatment of NAFLD were explored by network pharmacological methods. Gene ontology （GO） functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analysis were also performed. Based on the results obtained from network pharmacological studies， using SD rats as subjects， the NAFLD model was induced by feeding them high-fat diet. The effects of Sanqi danshen tablets on pathological changes such as lipid droplet vacuoles and lipid accumulation in the liver tissue of NAFLD rats， as well as its impact on relative indicators of lipid metabolism， inflammatory responses and oxidative stress， were investigated. RESULTS A total of 20 core targets for the treatment of NAFLD with Sanqi danshen tablets were screened， primarily involved in GO functions such as biological regulation， cellular membrane and binding， and enriched in signaling pathways related to inflammatory responses， oxidative stress and lipid metabolism. Compared with the model group， lipid droplet vacuoles were reduced significantly in low-dose， medium-dose， high-dose groups of Sanqi danshen tablets and positive control （simvastatin） group， the number of lipid droplets decreased significantly and the color became lighter. The contents of total cholesterol， triglyceride （except for medium- dose group of Sanqi danshen tablets）， aspartate transaminase， alanine transaminase， tumor necrosis factor-α （except for low-dose group of Sanqi danshen tablets）， interleukin-17 （except for Sanqi danshen tablets groups） and malondialdehyde （except for low- dose group of Sanqi danshen tablets） in liver tissue were significantly decreased， while the content of superoxide dismutase was significantly increased （P＜0.01 or P＜0.05）. CONCLUSIONS Sanqi danshen tablets exert anti-inflammatory， antioxidant and lipid metabolism regulating effects by influencing the levels of inflammation， oxidative stress and lipids metabolism-related indicators， thereby improving NAFLD in rats.

OBJECTIVE: To investigate the genetic causal relationship of leukocyte telomere length (LTL) with prostatitis, orchitis and epididymitis by two-sample Mendelian randomization (MR). METHODS: Using LTL as the exposure factor and prostatitis, orchitis and epididymitis as outcome factors, we mined the Database of Genome-Wide Association Studies (GWAS). Then, we analyzed the causal relationship of LTL with prostatitis, orchitis and epididymitis by Mendelian randomization using inverse variance weighting (IVW) as the main method and weighted median and MR-Egger regression as auxiliary methods, determined the horizontal multiplicity by MR-Egger intercept test, and conducted sensitivity analysis using the leaving-one-out method. RESULTS: A total of 121 related single nucleotide polymorphisms (SNPs) were identified in this study. IVW showed LTL to be a risk factor for prostatitis (OR = 1.383, 95% CI: 1.044－1.832, P = 0.024), and for orchitis and epididymitis as well (OR = 1.770, 95% CI: 1.275－2.456, P = 0.000 6). CONCLUSION Genetic evidence from Mendelian randomized analysis indicates that shortening of LTL reduces the risk of prostatitis, orchitis and epididymitis.
Humans ; Male ; Mendelian Randomization Analysis ; Epididymitis/genetics* ; Prostatitis/genetics* ; Polymorphism, Single Nucleotide ; Leukocytes ; Orchitis/genetics* ; Genome-Wide Association Study ; Telomere ; Risk Factors

Pyroptosis is an identified programmed cell death that has been highly linked to endoplasmic reticulum (ER) dynamics. However, the crucial proteins for modulating dynamic ER membrane curvature change that trigger pyroptosis are currently not well understood. In this study, a biotin-labeled chemical probe of potent pyroptosis inducer α-mangostin (α-MG) was synthesized. Through protein microarray analysis, reticulon-4 (RTN4/Nogo), a crucial regulator of ER membrane curvature, was identified as a target of α-MG. We observed that chemically induced proteasome degradation of RTN4 by α-MG through recruiting E3 ligase UBR5 significantly enhances the pyroptosis phenotype in cancer cells. Interestingly, the downregulation of RTN4 expression significantly facilitated a dynamic remodeling of ER membrane curvature through a transition from tubules to sheets, consequently leading to rapid fusion of the ER with the cell plasma membrane. In particular, the ER-to-plasma membrane fusion process is supported by the observed translocation of several crucial ER markers to the "bubble" structures of pyroptotic cells. Furthermore, α-MG-induced RTN4 knockdown leads to pyruvate kinase M2 (PKM2)-dependent conventional caspase-3/gasdermin E (GSDME) cleavages for pyroptosis progression. In vivo, we observed that chemical or genetic RTN4 knockdown significantly inhibited cancer cells growth, which further exhibited an antitumor immune response with anti-programmed death-1 (anti-PD-1). In translational research, RTN4 high expression was closely correlated with the tumor metastasis and death of patients. Taken together, RTN4 plays a fundamental role in inducing pyroptosis through the modulation of ER membrane curvature remodeling, thus representing a prospective druggable target for anticancer immunotherapy.
Pyroptosis/immunology* ; Humans ; Endoplasmic Reticulum/immunology* ; Animals ; Nogo Proteins/antagonists & inhibitors* ; Mice ; Cell Line, Tumor ; Xanthones/pharmacology* ; Neoplasms/pathology* ; Mice, Nude

Gastric cancer with peritoneal metastasis (GCPM) is a common and lethal manifestation of advanced gastric cancer, with a median survival of only 5-11 months. This consensus was developed by 30 experts from Asia (China, Japan, Korea, and Singapore) using the Delphi method and the GRADE evidence grading system. A total of 29 statements were formulated, covering the diagnosis and assessment of GCPM, indications for laparoscopic exploration and NIPS (normothermic intraperitoneal and systemic treatment), treatment regimens, prevention and management of complications, criteria for conversion surgery, and postoperative intraperitoneal therapy. The consensus aims to standardize clinical practice and improve the prognosis of patients with GCPM.

Objective Melatonin has been shown to have neuroprotective effects.This study is aimed at observing the effects of copper deposition on cognitive function in a toxic milk(TX)mouse model of Wilson disease(WD),and investigating the effects and mechanisms of action of Gandou Bushen Decoction(GDBSD)on melatonin synthesis and pineal function in the WD model mice.Methods A total of 30 homozygous TX mice were randomly assigned to 3 groups(n=10 in each group),including a WD group,a GDBSD group,and a dimercaptosuccinic acid(DMSA)group.A total of 10 DL mice were included in the normal control(NC)group.The structure and copper content of pineal gland tissues,oxidative stress and apoptosis-related markers,and serum melatonin levels were evaluated using hematoxylin-eosin(HE)staining,enzyme-linked immunosorbent assay(ELISA),flow cytometry,and Western blot.Results Compared with the NC group,the WD group exhibited decreased learning and cognitive abilities(P＜0.05),damaged pineal gland structure,increased copper content,reactive oxygen species(ROS)levels,and mitochondrial damage rate in the pineal gland(P＜0.01),altered levels of melatonin and oxidative stress-related markers(P＜0.05),upregulated expression levels of pro-apoptotic proteins Bax and Caspase-3,and decreased expression of the anti-apoptotic protein Bcl-2(P＜0.01).After treatment with GDBSD and DMSA,the SIRT3/FOXO3α signaling pathway was activated,the copper content in the pineal gland was reduced,and oxidative stress and apoptosis-related damages were improved,leading to an improvement in learning and memory abilities(P＜0.05).Conclusion GDBSD can alleviate cognitive impairments in WD mice caused by pineal gland copper deposition by inhibiting oxidative stress and apoptosis in the pineal gland.The underlying molecular mechanism is associated with the regulation of the SIRT3/FOXO3α signaling pathway.

Sorting out and analyzing the current research status of cost management and driver theory in domes-tic public hospitals,exploring new models of cost management in public hospitals,constructing a cost driver library for public hospitals,classifying various types of costs according to different driving factors,and adopting different cost management strategies for costs at different driver levels.To clarify the logical path between cost types,cost drivers,and cost strategies,and based on this,form a logical relationship model for cost management in public hos-pitals based on cost driver theory.Through the practical application of the hospital case,the feasibility and effective-ness have been verified.

Sorting out and analyzing the current research status of cost management and driver theory in domes-tic public hospitals,exploring new models of cost management in public hospitals,constructing a cost driver library for public hospitals,classifying various types of costs according to different driving factors,and adopting different cost management strategies for costs at different driver levels.To clarify the logical path between cost types,cost drivers,and cost strategies,and based on this,form a logical relationship model for cost management in public hos-pitals based on cost driver theory.Through the practical application of the hospital case,the feasibility and effective-ness have been verified.

Sorting out and analyzing the current research status of cost management and driver theory in domes-tic public hospitals,exploring new models of cost management in public hospitals,constructing a cost driver library for public hospitals,classifying various types of costs according to different driving factors,and adopting different cost management strategies for costs at different driver levels.To clarify the logical path between cost types,cost drivers,and cost strategies,and based on this,form a logical relationship model for cost management in public hos-pitals based on cost driver theory.Through the practical application of the hospital case,the feasibility and effective-ness have been verified.

Sorting out and analyzing the current research status of cost management and driver theory in domes-tic public hospitals,exploring new models of cost management in public hospitals,constructing a cost driver library for public hospitals,classifying various types of costs according to different driving factors,and adopting different cost management strategies for costs at different driver levels.To clarify the logical path between cost types,cost drivers,and cost strategies,and based on this,form a logical relationship model for cost management in public hos-pitals based on cost driver theory.Through the practical application of the hospital case,the feasibility and effective-ness have been verified.