ObjectiveTo explore the mechanism of herbal cake-separated moxibustion using the classical formula Xiaoyaosan in alleviating neuroimmune inflammatory responses in chronic fatigue syndrome （CFS） rats， based on the regulation of the toll-like receptor 4 （TLR4）/myeloid differentiation factor 88 （MyD88）/nuclear transcription factor-κB （NF-κB） signaling pathway. MethodsFifty SPF-grade SD rats aged 6-8 weeks were randomly divided into five groups： Normal group， model group， sham herbal cake moxibustion group， Chinese medicine intragastric administration group， and herbal cake-separated moxibustion group， with 10 rats in each group. Except for the normal group， all other groups underwent a 21-day modeling process， followed by behavioral testing. The herbal cake-separated moxibustion and sham herbal cake moxibustion groups received interventions at the Shenque （CV8）， Guanyuan （CV4）， Zusanli （ST36）， and Qimen （LR14） acupoints. The Chinese medicine intragastric administration group was treated with a Xiaoyaosan suspension via gavage. Behavioral tests were conducted after 10 days of continuous intervention. Serum levels of interleukin （IL）-1β， IL-6， and tumor necrosis factor-α （TNF-α）， as well as hippocampal levels of IL-1β， IL-6， TNF-α， and NF-κB， were detected by enzyme-linked immunosorbent assay （ELISA）. Morphological changes in the hippocampus were observed using hematoxylin-eosin （HE） staining. Real-time quantitative polymerase chain reaction （Real-time PCR） was used to detect mRNA expression levels of TLR4， MyD88， and NF-κB in the hippocampus. Western blot analysis was performed to detect the relative expression levels of TLR4， MyD88， NF-κB， and p65 proteins in the hippocampus. ResultsCompared with the normal group， the model group showed a significant decrease in upright times during the open field test （P<0.01）， as well as significant reductions in total movement distance， resting time， and center region duration （P<0.01）. In the tail suspension test， immobility time increased （P<0.01）， and struggle times decreased （P<0.01）. Serum and hippocampal levels of IL-1β， IL-6， and TNF-α， as well as hippocampal NF-κB levels and TLR4， MyD88， and NF-κB mRNA expression， were significantly elevated （P<0.01）. After treatment， compared with the model group， the total movement distance and upright times in the open field test were significantly increased in all treatment groups （P<0.01）， while resting time and center region duration were notably prolonged （P<0.05， P<0.01）. Immobility time in the tail suspension test was significantly shortened （P<0.01）， and struggle times significantly increased （P<0.05）. Serum and hippocampal levels of IL-1β， IL-6， TNF-α， hippocampal NF-κB levels， and TLR4 and NF-κB mRNA expression were significantly reduced （P<0.05， P<0.01）. Compared with the sham herbal cake moxibustion group， the herbal cake-separated moxibustion group showed a significant extension in center region duration during the open field test （P<0.05） and a significant increase in upright times （P<0.01）. In the tail suspension test， immobility time was reduced （P<0.01）， and struggle times increased （P<0.01）. Serum TNF-α levels in the Chinese medicine intragastric administration group were significantly reduced （P<0.01）， while serum IL-6 levels， as well as hippocampal levels of IL-1β， TNF-α， NF-κB， and TLR4， MyD88， and NF-κB mRNA expression， were significantly decreased in both the Chinese medicine intragastric administration group and the herbal cake-separated moxibustion group （P<0.05， P<0.01）. Compared with the Chinese medicine intragastric administration group， the herbal cake-separated moxibustion group exhibited significantly increased upright times in the open field test （P<0.01）. In the tail suspension test， immobility time was reduced （P<0.01）， and struggle times increased （P<0.01）. Serum IL-1β， hippocampal TNF-α levels， and TLR4， MyD88， and NF-κB mRNA expression were significantly decreased （P<0.05， P<0.01）. ConclusionHerbal cake-separated moxibustion effectively improves fatigue and memory function in CFS rats， regulates neuroimmune inflammatory responses， and its mechanism may be related to the modulation of the TLR4/MyD88/NF-κB signaling pathway.

ObjectiveTo explore the mechanism of moxibustion with the classical prescription Xiaoyaosan as the herbal cake in improving cognitive function in the rat model of chronic fatigue syndrome （CFS） by regulating autophagy via phosphatidylinosiol 3-kinase （PI3K）/autophagy key molecule yeast Atg6 homologue 1 （Beclin1） signaling pathway. MethodsFifty SPF-grade SD rats aged 6-8 weeks were randomly grouped as follows： control， model， sham cake-separated moxibustion， intragastric administration with Chinese herbs， and herbal cake-separated moxibustion， each with 10 rats. The other groups except the control group were subjected to modeling by exhaustive swimming and chronic restraint stress for 21 days， and the behavioral test was performed after modeling. Herbal cake-separated moxibustion and sham cake-separated moxibustion were carried out at Shenque （CV8）， Guanyuan （CV4）， Zusanli （ST36）， and Qimen （LR14）. The rats in the intragastric administration with Chinese herbs group were treated with Xiaoyaosan suspension by gavage. After continuous intervention for 10 days， rat behaviors were observed and the levels of interleukin （IL）-4， IL-10， blood urine nitrogen （BUN）， and malondiadehyde （MDA） in the serum and hippocampal tissue of rats in each group were determined by enzyme-linked immunosorbent assay. The morphological changes of the hippocampal tissue were observed by hematoxylin-eosin staining. The relative mRNA and protein levels of PI3K and Beclin1 in the hippocampal tissue were determined by Real-time quantitative polymerase chain reaction （Real-time PCR） and Western blot， respectively. ResultsCompared with the normal group， the model group showed reduced crossings， shortened residence time in the target quadrant， and prolonged average escape latency on days 1， 2， 3， and 4 （P<0.01） in the Morris water maze test. In the new object recognition test， the model group showed decreased recognition index of exploration time and recognition index of exploration times （P<0.01）， lowered levels of IL-4 and IL-10 and elevated levels of BUN and MDA in the serum and hippocampus （P<0.01）， and down-regulated mRNA and protein levels of PI3K and Beclin1 （P<0.01）. After treatment， compared with the model group， each treatment group showed increased crossings， prolonged residence time in the target quadrant， and shortened average escape latency on days 1， 2， 3， and 4 （P<0.05， P<0.01）. In addition， the treatment elevated the levels of IL-4 and IL-10 and lowered the levels of BUN and MDA in the serum and hippocampus （P<0.05， P<0.01）， and up-regulated the mRNA and protein levels of PI3K and Beclin1 （P<0.05， P<0.01）. Compared with the sham cake-separated moxibustion group， the herbal cake-separated moxibustion group and the intragastric administration with Chinese herbs group showed increased crossings， prolonged residence time in the target quadrant （P<0.05）， elevated level of IL-4， lowered level of MDA， and up-regulated relative mRNA and protein levels of PI3K and Beclin1 in the hippocampus （P<0.05， P<0.01）. The serum levels of MDA and BUN in the intragastric administration with Chinese herbs group were significantly decreased. The average escape latency of the herbal cake-separated moxibustion group was significantly shortened on days 2 and 3 （P<0.05， P<0.01）. In addition， this group showed elevated serum level of IL-4， lowered serum level of MDA， and declined BUN level in the hippocampus （P<0.05， P<0.01）. Compared with the intragastric administration with Chinese herbs group， the herbal cake-separated moxibustion group presented risen serum level of IL-4 and up-regulated mRNA level of Beclin1 （P<0.05） and relative protein levels of PI3K and Beclin1 （P<0.05， P<0.01）. ConclusionHerbal cake-separated moxibustion can effectively alleviate fatigue and improve the memory， reduce inflammatory response and oxidative stress， and decrease autophagy of hippocampal neurons in CFS rats by regulating the PI3K/Beclin1 signaling pathway.

ObjectiveTo explore the mechanism of moxibustion with the classical prescription Xiaoyaosan as the herbal cake in improving cognitive function in the rat model of chronic fatigue syndrome （CFS） by regulating autophagy via phosphatidylinosiol 3-kinase （PI3K）/autophagy key molecule yeast Atg6 homologue 1 （Beclin1） signaling pathway. MethodsFifty SPF-grade SD rats aged 6-8 weeks were randomly grouped as follows： control， model， sham cake-separated moxibustion， intragastric administration with Chinese herbs， and herbal cake-separated moxibustion， each with 10 rats. The other groups except the control group were subjected to modeling by exhaustive swimming and chronic restraint stress for 21 days， and the behavioral test was performed after modeling. Herbal cake-separated moxibustion and sham cake-separated moxibustion were carried out at Shenque （CV8）， Guanyuan （CV4）， Zusanli （ST36）， and Qimen （LR14）. The rats in the intragastric administration with Chinese herbs group were treated with Xiaoyaosan suspension by gavage. After continuous intervention for 10 days， rat behaviors were observed and the levels of interleukin （IL）-4， IL-10， blood urine nitrogen （BUN）， and malondiadehyde （MDA） in the serum and hippocampal tissue of rats in each group were determined by enzyme-linked immunosorbent assay. The morphological changes of the hippocampal tissue were observed by hematoxylin-eosin staining. The relative mRNA and protein levels of PI3K and Beclin1 in the hippocampal tissue were determined by Real-time quantitative polymerase chain reaction （Real-time PCR） and Western blot， respectively. ResultsCompared with the normal group， the model group showed reduced crossings， shortened residence time in the target quadrant， and prolonged average escape latency on days 1， 2， 3， and 4 （P<0.01） in the Morris water maze test. In the new object recognition test， the model group showed decreased recognition index of exploration time and recognition index of exploration times （P<0.01）， lowered levels of IL-4 and IL-10 and elevated levels of BUN and MDA in the serum and hippocampus （P<0.01）， and down-regulated mRNA and protein levels of PI3K and Beclin1 （P<0.01）. After treatment， compared with the model group， each treatment group showed increased crossings， prolonged residence time in the target quadrant， and shortened average escape latency on days 1， 2， 3， and 4 （P<0.05， P<0.01）. In addition， the treatment elevated the levels of IL-4 and IL-10 and lowered the levels of BUN and MDA in the serum and hippocampus （P<0.05， P<0.01）， and up-regulated the mRNA and protein levels of PI3K and Beclin1 （P<0.05， P<0.01）. Compared with the sham cake-separated moxibustion group， the herbal cake-separated moxibustion group and the intragastric administration with Chinese herbs group showed increased crossings， prolonged residence time in the target quadrant （P<0.05）， elevated level of IL-4， lowered level of MDA， and up-regulated relative mRNA and protein levels of PI3K and Beclin1 in the hippocampus （P<0.05， P<0.01）. The serum levels of MDA and BUN in the intragastric administration with Chinese herbs group were significantly decreased. The average escape latency of the herbal cake-separated moxibustion group was significantly shortened on days 2 and 3 （P<0.05， P<0.01）. In addition， this group showed elevated serum level of IL-4， lowered serum level of MDA， and declined BUN level in the hippocampus （P<0.05， P<0.01）. Compared with the intragastric administration with Chinese herbs group， the herbal cake-separated moxibustion group presented risen serum level of IL-4 and up-regulated mRNA level of Beclin1 （P<0.05） and relative protein levels of PI3K and Beclin1 （P<0.05， P<0.01）. ConclusionHerbal cake-separated moxibustion can effectively alleviate fatigue and improve the memory， reduce inflammatory response and oxidative stress， and decrease autophagy of hippocampal neurons in CFS rats by regulating the PI3K/Beclin1 signaling pathway.

OBJECTIVES: As early as the Apollo 11 mission, astronauts experienced ocular, skin, and upper airway irritation after lunar dust (LD) was brought into the return cabin, drawing attention to its potential biological toxicity. However, the biological effects of LD exposure through the digestive system remain poorly understood. This study aimed to evaluate the impact of digestive exposure to lunar dust simulant (LDS) on gut microbiota and on the intestine, liver, kidney, lung, and bone in mice. METHODS: Eight-week-old female C57BL/6J mice were used. LDS was used as a substitute for lunar dust, and Shaanxi loess was used as Earth dust (ED). Mice were randomly divided into a phosphate buffered saline (PBS) group, an ED group (500 mg/kg), and a LDS group (500 mg/kg), with assessments at days 7, 14, and 28. Mice were gavaged once every 3 days, with body weight recorded before each gavage. At sacrifice, fecal samples were analyzed by 16S ribosomal RNA (rRNA) sequencing; inflammatory cytokine expression [interleukin (IL)-1β, IL-6, and tumor necrosis factor alpha (TNF-α)] in intestinal, liver, and lung tissues was measured by real-time reverse transcription PCR (real-time RT-PCR); hematoxylin and eosin (HE) staining was performed on lung, liver, and intestinal tissues; Periodic acid-Schiff (PAS) staining was used to assess the integrity of the intestinal mucus barrier, and immunohistochemical staining was performed to evaluate the expression of mucin-2 (MUC2). Serum biochemical tests assessed hepatic and renal function. Femoral bone mass was analyzed by micro-computed tomography (micro-CT); osteoblasts and osteoclasts were assessed by osteocalcin (OCN) and tartrate-resistant acid phosphatase (TRAP) staining. Bone marrow immune cell subsets were analyzed by flow cytometry. RESULTS: At day 10, weight gain was slowed in ED and LDS groups. At days 22 and 28, body weight in both ED and LDS groups was significantly lower than controls (both P<0.05). LDS exposure increased microbial species richness and diversity at day 7. Compared with the PBS and ED groups, mice in the LDS group showed increased relative abundance of Deferribacterota, Desulfobacterota, and Campylobacterota, and decreased Firmicutes, with increased Helicobacter typhlonius and reduced Lactobacillus johnsonii and Lactobacillusmurinus. HE and PAS staining of the colon showed that mucosal structural disruption and goblet cell loss were more severe in the LDS group. In addition, immunohistochemistry revealed a significant downregulation of MUC2 expression in this group (P<0.05). No obvious pathological alterations were observed in liver HE staining among the 3 groups, and none of the groups exhibited notable hepatic or renal dysfunction. HE staining of the lungs in the ED and LDS groups showed increased perivascular inflammatory cell infiltration (both P<0.05). CONCLUSIONS LDS exposure via the digestive route induces gut dysbiosis, intestinal barrier disruption, pulmonary inflammation, bone loss, and bone marrow immune imbalance. These findings indicate that LD exposure poses potential health risks during future lunar missions. Targeted restoration of beneficial gut microbiota may represent a promising strategy to mitigate LD-related health hazards.
Animals ; Dust ; Mice ; Mice, Inbred C57BL ; Dysbiosis/etiology* ; Female ; Gastrointestinal Microbiome/drug effects* ; Moon ; Liver/metabolism* ; Digestive System/microbiology* ; Lung/metabolism* ; Kidney

OBJECTIVES: Due to prolonged exposure to cosmic radiation and meteorite impacts, lunar surface dust forms nanoscale angular particles with strong electrostatic adsorption properties. These dust particles pose potential inhalation risks, yet their pulmonary toxicological mechanisms remain unclear. Given the need for dust exposure protection in future lunar base construction and resource development, this study established an acute exposure model using lunar soil simulant (LSS) and used Earth soil (ES; Loess from Shaanxi, China) as a comparison to investigate lung injury mechanisms. METHODS: C57BL/6 mice were randomly assigned to 3 groups: Phosphate buffered saline (PBS), LSS, and ES, with 5 to 7 mice per group. Mice in the LSS and ES groups received a single intratracheal instillation to induce acute inhalation exposure. Body weight was monitored for 28 days. Mice were euthanized at days 3, 7, 14, and 28 post-exposure, and peripheral blood, bronchoalveolar lavage fluid (BALF), and lung tissues were collected. Immune cell subsets in BALF were analyzed using flow cytometry. Hematoxylin-eosin (HE) staining assessed lung structure and inflammation; periodic acid-Schiff (PAS) staining evaluated airway mucus secretion; Masson staining examined collagen deposition. Real-time reverse transcription PCR (real-time RT-PCR) was used to measure the mRNA expression of inflammatory cytokines (IL-1β, IL-6, and TNF-α) and epithelial barrier genes (Occludin, Cadherin-1, and Zo-1). Lung tissues at day 7 were subjected to transcriptomic sequencing, followed by immune infiltration and pathway enrichment analyses to determine immunoregulatory mechanisms. RESULTS: Body weight in the ES group progressively declined after day 18 (all P<0.05), while the LSS group showed no significant changes compared with the control group. HE staining showed both LSS and ES induced inflammatory cell infiltration around airways and vasculature, which persisted for 28 days but gradually lessened over time. PAS staining revealed marked mucus hypersecretion in the LSS group at day 3, followed by gradual recovery; no significant mucus changes were observed in the ES group. Masson staining indicated no obvious pulmonary fibrosis in either group within 28 days. Real-time RT-PCR demonstrated significant upregulation of IL-1β and TNF-α in both LSS and ES groups, peaking on day 7, accompanied by downregulation of epithelial barrier genes (Occludin, Cadherin-1, and Zo-1)(all P<0.05). Transcriptomic analysis showed that both LSS and ES activated chemokine-related pathways and enriched leukocyte migration and neutrophil recruitment pathways. Further validation revealed upregulation of CXCL2 and MMP12 in the LSS group, whereas CXCL3 and MMP12 were predominantly elevated in the ES group. CONCLUSIONS Both LSS and ES can induce sustained lung injury and neutrophil infiltration in mice, though the underlying molecular mechanisms differ. Compared with ES, exposure to LSS additionally triggers a transient eosinophilic response, suggesting that lunar dust particles possess stronger immunostimulatory potential and higher biological toxicity.
Animals ; Mice ; Mice, Inbred C57BL ; Soil ; Lung Injury/etiology* ; Dust ; Bronchoalveolar Lavage Fluid ; Moon ; Lung/pathology* ; Inhalation Exposure/adverse effects* ; Male

Regulated cell death (RCD) is a critical physiological process essential in maintaining skin homeostasis. Among the various forms of RCD, ferroptosis stands out due to its distinct features of iron accumulation, lipid peroxidation, and involvement of various inhibitory antioxidant systems. In recent years, an expanding body of research has solidly linked ferroptosis to the emergence of skin disorders. Therefore, understanding the mechanisms underlying ferroptosis in skin diseases is crucial for advancing therapy and prevention strategies. This review commences with a succinct elucidation of the mechanisms that underpin ferroptosis, embarks on a thorough exploration of ferroptosis’s role across a spectrum of skin conditions, encompassing melanoma, psoriasis, systemic lupus erythematosus (SLE), vitiligo, and dermatological ailments precipitated by ultraviolet (UV) exposure, and scrutinizes the potential therapeutic benefits of pharmacological interventions aimed at modulating ferroptosis for the amelioration of skin diseases.

Objective To investigate the genetic causal relationship between rheumatoid arthritis (RA) and its serological antibody levels with pre-eclampsia (PE) based on Mendelian randomization (MR). Methods Single nucleotide polymorphism (SNP) with significant differences were screened as instrumental variables,and the five MR analytic method with the inverse variance weighting (IVW) as the main analytical method were applied to comprehensively assess the causal cc relationship between OA,serum antibody levels PE.The MR-Egger intercept method,MR pleiotropy residual and outlier (MR-PRESSO) method,Cochrane's Q-test were applied to explore the horizontal pleiotropy and heterogeneity of SNP,and the leave-one-out meth-od was used to explore the effect of individual SNPs on MR results.Results The IVW result indicated that RA (OR=1.098,95％CI:1.036-1.164,P=0.002) and seropositive RA (OR=1.088,95％CI:1.026-1.153,P=0.005) were the PE risk factors,whereas seronegative RA (OR=1.036,95％CI:0.971-1.104, P=0.282) did not have a significant causal relationship with PE.No significant level pleiotropy or heteroge-neity was found in the SNPs used in MR analyses of the 3 exposure factors.rs34434863 played a decisive role in the causal relationship of RA and seropositive RA with PE.Conclusion Based on MR analysis,there is a significant positive causal relationship between RA and seropositive RA with PE,whereas there was no signifi-cant causal relationship between seronegative RA and PE.

Objective:To conduct visualization analysis,induction and summary for the study status,focus and trend in the dose measurement field of flash radiotherapy(Flash-RT)through bibliometric methods on the basis of the Web of Science Collection(WOS),and analyze the technical bottleneck of Flash-RT dose measurement.Methods:In the WOS database,the("FLASH radiotherapy"or"ultra high dose rate"or"FLASH irradiation")and TS=("dosimetric system"or"dosimeters"or"dosimetry")were used as the theme terms,and all relevant literatures about the study of Flash-RT dose measurement that were included in the Core Collection of WOS database were retrieved.The citation analysis function of WOS and Citespace software(Version 6.2)were used to conduct visualization analysis for the publication trends,sources and research focus of the included literature of Flash-RT dose measurement,and to draw corresponding visualization knowledge maps.Results:The literatures were mainly published during January 2015 and November 2023,and a total of 86 papers were included in the analysis by screening,which included 78 articles and 8 reviews.The top three countries in terms of publication volume were respectively the United States(38 papers),France(19 papers)and Italy(19 papers).The research focuses were respectively Cherenkov,radiotherapy,passive dosimeter,conventional radiation,laser particle acceleration,ionization chamber and proton therapy as cluster analysis.Currently,the study of Flash-RT dose measurement mainly focused on the relevant fields included Flash-RT radiation source,dose rate,and the equipment and method of dose measurement.Conclusion:Flash-RT is a new technology with a key breakthrough in the basic field of radiotherapy,and this technique faces many difficulties and challenges in the clinical translation process of this technique.With the continuous development of science and technique,and deepeningaccumulation of related researchclinical big data,the method and procedure of accurate and efficient dose measurement dosimetry methods and procedures will promote and realize the update and iteration of Flash-RT experiment research and device technique,which will successfully realize the clinical the broader application prospects of this technology.

Objective:To prevent postoperative myocardial oedema or other causes of acute heart failure in congenital cardiac disease,anticipating delay sternal closure may reduce the number of children requiring cardiopulmonary resuscitation after surgery.The aim of this study was to describe the rate of delay sternal closure after surgery for congenital cardiac disease and to analyse the risk factors that may be associated with it.Methods:We retrospectively reviewed all surgeries with extracorporeal circulation in the cardiothoracic surgery intensive care unit of Shanghai Children's Medical Center in the past five years,from September 2014 to December 2018.The study cohort was divided into the delay sternal closure group (n=418) and the control group (routine chest closure,n=12 188) according to whether a delay sternal closure was applicated.Risk factors associated with delay sternal closure were identified by multivariate Logistic regression analysis.Results:A total of 12 606 cases were eligible,of which 418 (3.32%) were in the delayed sternal closure group.The most common cardiac diagnosis in the delayed sternal group was transposition of the great arteries (26.8%,112/418),whereas the most common cardiac diagnosis in the control group was ventricular septal defect (45.9%,5 599/12 188).All-cause mortality in children in the delayed sternal closure group was 3.3% (14/418) compared with 0.4% (46/12 188) in the control group,with a statistically significant difference ( P<0.05).Multivariate Logistic regression analysis showed that the need for delayed sternal closure were associated with age ( OR 0.164,95% CI 0.079-0.338, P<0.001),positive intropic support before surgery ( OR 0.42,95% CI 0.252-0.699, P=0.001),sex（ OR 0.742，95% CI 0.648-1.098， P<0.05），mean body weight（ OR 1.192，95% CI 1.078-1.318， P<0.001），positive intropic support before surgery（ OR 0.370，95% CI 0.252-0.699， P<0.001），complicated surgery ( OR 0.241,95% CI 0.159-0.367, P<0.001) and extracorporeal circulation diversion time ( OR 6.412,95% CI 4.339-9.475, P<0.001). Conclusion:Delayed sternal closure is an important management strategy for congenital cardiac surgery in infants and children.Delayed sternal closure is associated with age，sex,mean body weight at the time of surgery,positive intropic support before surgery，complicated surgery and extracorporeal circulation diversion time.

Psychotherapy is one of the widely used therapies for depression.Yet there are currently no definitive biological markers as indicators of effectiveness.Using functional magnetic resonance imaging(fMRI)to assess the neuroimaging biomarkers before and after different psychological treatments for depression reveals corresponding changes in brain region activation and functional connectivity.For example,after cognitive-behavioral therapy,the prefrontal cortex of patients may be activated and dynamic functional connectivity variability may change,while mindfulness therapy may show alterations in specific temporal lobe regions.Additionally,studies exploring special populations and internet-based psychological intervention have also found changes in brain region activation and functional connectivity,providing guidance for the efficacy evaluation of corresponding psychotherapies.This article reviews the characteristic brain region or network changes in fMRI activity after different psychotherapies in depressed patients,aiming to discuss future directions for research that integrates neuroimaging with psychological treatment for depression.