Objective To investigate the expression profile, prognostic value, gene co-expression network, and immunomodulatory role of BRF1 in a pan-cancer context, and to explore its biological functions and molecular regulatory mechanisms in esophageal squamous cell carcinoma (ESCC). Methods The pan-cancer dataset from The Cancer Genome Atlas (TCGA) was utilized to analyze the differential expression of BRF1 in tumor versus normal tissues, its association with patient survival, pathway enrichment for co-expressed genes, and immune features (including immune checkpoints, cytokines, and immune cell infiltration). The expression profile of BRF1 in ESCC was validated using the Gene Expression Omnibus (GEO) database. In vitro, BRF1 was knocked down in ESCC cells using siRNA. Cell proliferation and migration were assessed by MTT and Transwell assays, respectively. The expression levels of proliferation- and migration-related proteins were detected by Western blotting. The correlation between BRF1 and ferroptosis was analyzed using TCGA data. Results BRF1 was significantly upregulated in over 20 types of cancer, and its high expression was associated with poor prognosis in patients with adrenocortical carcinoma and prostate adenocarcinoma. BRF1 was found to positively regulate the T-cell-mediated cell death pathway in esophageal adenocarcinoma and was associated with the circadian rhythm regulation pathway in pancreatic adenocarcinoma. The correlation of BRF1 with immune checkpoints, cytokine networks, and immune cell infiltration was found to be cancer type-specific. In vitro experiments demonstrated that knocking down BRF1 significantly inhibited the proliferation of ESCC cells, accompanied by the downregulation of the proliferation marker PCNA. Cell migration was also significantly impaired, with decreased expression of Vimentin and MMPs and increased expression of E-cadherin. Furthermore, the expression of BRF1 was positively correlated with that of ferroptosis-antagonizing genes, such as GPX4, HSPA5, and SLC7A11. Conclusion BRF1 plays complex roles in pan-cancer, participating in the regulation of tumorigenesis, progression, and immune infiltration. BRF1 promotes the proliferation and migration of ESCC cells, a mechanism potentially associated with the regulation of ferroptosis resistance. These findings suggest that BRF1 could be a potential therapeutic target for ESCC.

ObjectiveTo investigate the effect and mechanism of modified Sini San in ameliorating intestinal mucosal barrier by observing its effects on short chain fatty acids （SCFAs） and high mobility group protein B1 （HMGB1）/receptor of advanced glycation end products （RAGE） signaling pathways in chronic stress rats. MethodsThe 50 male SD rats were randomly divided into control group，model group，low-dose modified Sini San group （7.34 g·kg^-1·d^-1），high-dose modified Sini San group （14.68 g·kg^-1·d^-1），and Fructo-oligosaccharides group （3.15 g·kg^-1·d^-1），with 10 rats in each group. Except for the control group，all other groups were subjected to chronic unpredictable stress/social isolation to create a chronic stress model for 6 weeks. After 4 weeks of modeling，each treatment group was given corresponding drugs by gavage for 2 weeks while modeling. The control group and model group were given the same volume of physiological saline. The effects of Modified Sini San on behaviors，body weight，Bristol score in feces and fecal moisture content in chronic stress rats were observed. Hematoxylin and eosin （HE） staining was used to observe the pathological changes in the cecum. The content of SCFAs in the cecal contents of rats were detected by Gas chromatography-mass spectrometry （GC-MS）. Immunohistochemistry and Western blot were used to detect the expression of HMGB1/RAGE pathway related proteins in cecal tissue. The levels of ZO-1，Occludin，and Claudin-1 in the cecal tissue were detected by enzyme linked immunosorbent assay （ELISA）. ResultsCompared with the model group，the sucrose preference rate，total distance traveled and the number of grid crossings in the open field test of rats in the low-dose modified Sini San group were obviously increased （P<0.05， P<0.01），and the immobility time in the open field test and the immobility time in the forced swimming test of rats in the low-dose and high-dose modified Sini San groups were obviously reduced （P<0.05， P<0.01）. Meanwhile，the Bristol score and fecal moisture content of rats in the low and high dose groups of modified Sini San were obviously increased （P<0.05）. The low-dose group of modified Sini San had intact mucosal layer structure in the cecal tissue and reduced infiltration of inflammatory cells. The content of SCFAs in the cecal contents increased，with a obviously increase in the content of acetic acid，propionic acid，butyric acid，and isovaleric acid （P<0.05， P<0.01） and the expression levels of HMGB1，RAGE，Toll-like receptor 2（TLR2），Toll-like receptor 4（TLR4），tumor necrosis factor-α（TNF-α），and nuclear factor kappa-B p65（NF-κB p65） proteins in cecal tissue were significantly decreased （P<0.05， P<0.01） in low-dose group of modified Sini San. Meanwhile，the contents of ZO-1，Occludin，and Claudin-1 in the cecal tissue were obviously increased （P<0.01） in low-dose group of modified Sini San. ConclusionModified Sini San can improve the function of intestinal mucosal barrier in chronic stress rats by increasing the content of SCFAs in the intestine and inhibiting the HMGB1/RAGE pathway.

AIM:This study aimed to utilize network pharmacology and an anxiety rat model to investigate the intervention targets and underlying mechanisms of Baixiangdan capsule(BXD)in the treatment of anxiety-like behavior.METHODS:We screened the action targets of BXD on the anxiety model using network pharmacology,followed by Gene Ontology(GO)enrichment and the Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analysis of the identified targets.Additionally,we evaluated the effects of BXD on rat anxiety behaviors induced by foot shock,with measurement of serum level of c-Jun N-terminal kinase inhibitor(JIK),and the protein levels of c-Jun N-terminal kinase(JNK),phos-phorylated JNK(p-JNK)and JIK in the left hippocampus and hypothalamus.RESULTS:A total of 97 targets,including the dopamine D1/D3 receptors,were identified as intersection targets.GO enrichment analysis indicated that target pro-teins were significantly involved in molecular functions such as catecholamine binding,receptor activation,and signal transduction.KEGG pathway analysis revealed that neural receptor-ligand pathways,including dopaminergic synapses(15%)and neuroactive ligand-receptor interaction(18%),were notably represented.In behavioral experiments,BXD and diazepam treatments significantly reduced total path in the open-field test(P＜0.01),while the number of entries into the central region increased(P＜0.05).Additionally,the percentage of entry times of the open arm and the percentage of time spent in the open arm were also increased(P＜0.01).Furthermore,BXD treatment led to decreased ratio of p-JNK/JNK and increased level of JIK(P＜0.05).CONCLUSION:The traditional Chinese medicine BXD demonstrates a promising efficacy in alleviating anxiety-like behaviors in model rats.It operates through a multi-component,multi-target,and multi-pathway approach,primarily by modulating the JIK/JNK signaling pathway.

BACKGROUND:The incidence of inflammatory bowel disease has been steadily rising,accompanied by a lack of definitive therapeutic strategies.Recent research endeavors have illuminated the promising potential of mesenchymal stem cells in mitigating the symptoms of inflammatory bowel disease,offering a glimmer of hope for afflicted patients.OBJECTIVE:To review the mechanisms of action of mesenchymal stem cells derived from various sources in the management of inflammatory bowel disease,aiming to provide insights for future research endeavors.METHODS:Utilizing the keywords"mesenchymal stem cells,MSCs,exosomes,extracellular vesicles,EVs,inflammatory bowel disease,IBD,ulcerative colitis,UC,Crohn's disease,CD"in English and their Chinese equivalents in CNKI and PubMed databases,a total of 89 eligible articles were selected for this review.RESULTS AND CONCLUSION:Currently,six types of mesenchymal stem cells are being explored for inflammatory bowel disease therapy:bone marrow-derived mesenchymal stem cells,adipose tissue-derived mesenchymal stem cells,perinatal tissue-derived mesenchymal stem cells,induced pluripotent stem cell-derived mesenchymal stem cells,embryonic stem cell-derived mesenchymal stem cells,and gingival mesenchymal stem cells.Five administration routes have been adopted,with intravenous and intraperitoneal injections being the most prevalent,followed by local,mesenteric,and intra rectal injections.Their therapeutic mechanisms encompass differentiation,regeneration,anti-inflammatory effects,immune modulation,neuroprotection,antioxidant stress response,homing,modulation of gut microbiota,autophagy,ferroptosis,and endoplasmic reticulum stress.While sharing functional similarities,mesenchymal stem cells from different sources exhibit unique characteristics that confer them with distinct advantages and therapeutic potentials.Nevertheless,research into the specific properties of these mesenchymal stem cells remains limited,necessitating deeper exploration of their nuanced differences to optimize their therapeutic efficacy in inflammatory bowel disease.Additionally,the clinical safety of mesenchymal stem cells-based therapies warrants further observation and evaluation.

The triceps surae muscle-tendon unit(MTU)is the key for effective force generation,transmission,and energy storage and release in human movement,with great influences on sports efficiency,but its injury rate remains high.This review summarizes MTU function and its biomechanical adaptations during running,aiming to deepen the understanding of MTU's role in movement and explore how external factors influence its biomechanical properties,offering scientific insights for improving running performance and preventing injuries.During running,under forefoot striking and wearing shoes with greater stiffness,such as shoes with carbon plate,the energy contraction or return could be achieved through a more economical MTU behavior,namely reducing energy consumption by more economically muscle contraction and more energy storage of elastic elements,and the muscle contraction was exerted at a length closer to the optimal muscle fascicle length and reduced energy consumption caused by muscle contraction.However,adopting forefoot striking,barefoot running,or wearing minimalist shoes during running could increase the mechanical loads on the MTU.After gait retraining,the MTU could contract or return energy more efficiently during running,while the impact of other training methods on MTU was relatively poor,and the research in this area is still not sufficient.Therefore,future research should focus on optimizing the biomechanical properties of the MTU,MTU interaction and balanced development through changes in movement patterns,equipment,and training methods to enhance performance and reduce injuries.

Objective The aim of this study was to investigate the expression of nuclear pore membrane protein 121(POM121)in head and neck mucosal melanoma(HNMM)and its effect on the migration and invasion of HNMM cells.Methods The cancer tissues from 63 patients with HNMM and 20 adjacent normal oral epithelial tissues who were treated in the Harbin Cancer Hos-pital of Harbin Medical University from March 1,2011 to March 30,2015 were collected,and the expression of POM121 was detected by immunohistochemistry.The relationship between the expression of POM121 and the clinicopathological features of HNMM patients and its effect on the prognosis of patients were analyzed.Western blot was used to detect the expression of POM121 in HNMM cells(MM9H-1 cells)and human oral epithelial cells(human oral keratinocytes,HOK cells).After knocking down POM121 with small in-terfering RNA(siRNA),the effects on the migration and invasion of HNMM cells were detected by Scratch assay and Transwell assay.Results Immunohistochemistry showed that expression of POM121 was significantly higher in HNMM tissues than that in adjacent tissues(P<0.001).The expression of POM121 was associated with tumor size and stage(P<0.05).Kaplan-Meier analysis showed that the disease-free survival(DFS)and overall survival(OS)of patients with low expression of POM121 were significantly longer than those with high expression of POM121.Cox regression analysis showed that POM121 expression,AJCC stage and lymph node metasta-sis were influencing factors for OS and DFS of HNMM patients(P<0.05).Western blot results showed that the expression of POM121 protein in MM9H-1 cells was significantly higher than that in HOK cells(P<0.05).After knocking down POM121,the cell migration rate and cell invasion ability were significantly reduced(P<0.001).Conclusion POM121 is highly expressed in HNMM tissues and cells,and down-regulation of POM121 significantly inhibits the migration and invasion of HNMM cells.

Objective To explore the effect of exercise-induced fatigue on intra-and interhemispher-ic functional connectivity of the primary motor cortex during unilateral ankle plantar-dorsiflexion.Meth-ods Twenty-four healthy adult males(age:21.6±2.2 years;all right-side dominant)were selected as participants for the study.They ran on a treadmill at an individualized constant speed until fatigue.Fatigue was determined when all the following criteria were met:(1)participants failing to maintain the individualized constant speed despite the strong verbal encouragement from the experimenters;(2)reaching a rating of perceived exertion(RPE)score of at least 19;and(3)their heart rate reaching 90%of their age-predicted maximal heart rate(220-age).Moreover,EEG signals from four channels(C1,C2,C3,and C4)of the primary motor cortex were collected during unilateral ankle dorsi-plan-tarflexion movements before and after fatigue,followed by EEG coherence analyses on the collected da-ta.Results Compared to the pre-fatigue state,the coherence values of the intra-hemispheric primary motor cortex electrode pairs C1-C3 and C2-C4 during unilateral ankle plantar-dorsiflexion decreased significantly in the alpha and gamma bands after fatigue(both P<0.05).Conversely,the value of the interhemispheric primary motor cortex electrode pair C1-C2 increased significantly in the beta band(P<0.05).Conclusion Exercise-induced fatigue significantly weakens the intra-hemispheric functional con-nectivity of the primary motor cortex during unilateral ankle plantar-dorsiflexion.However,it may en-hance the interhemispheric functional connectivity and potentially collaborate to strengthen the regula-tion of fatigued muscles.

Objective To explore the effect of exercise-induced fatigue on intra-and interhemispher-ic functional connectivity of the primary motor cortex during unilateral ankle plantar-dorsiflexion.Meth-ods Twenty-four healthy adult males(age:21.6±2.2 years;all right-side dominant)were selected as participants for the study.They ran on a treadmill at an individualized constant speed until fatigue.Fatigue was determined when all the following criteria were met:(1)participants failing to maintain the individualized constant speed despite the strong verbal encouragement from the experimenters;(2)reaching a rating of perceived exertion(RPE)score of at least 19;and(3)their heart rate reaching 90%of their age-predicted maximal heart rate(220-age).Moreover,EEG signals from four channels(C1,C2,C3,and C4)of the primary motor cortex were collected during unilateral ankle dorsi-plan-tarflexion movements before and after fatigue,followed by EEG coherence analyses on the collected da-ta.Results Compared to the pre-fatigue state,the coherence values of the intra-hemispheric primary motor cortex electrode pairs C1-C3 and C2-C4 during unilateral ankle plantar-dorsiflexion decreased significantly in the alpha and gamma bands after fatigue(both P<0.05).Conversely,the value of the interhemispheric primary motor cortex electrode pair C1-C2 increased significantly in the beta band(P<0.05).Conclusion Exercise-induced fatigue significantly weakens the intra-hemispheric functional con-nectivity of the primary motor cortex during unilateral ankle plantar-dorsiflexion.However,it may en-hance the interhemispheric functional connectivity and potentially collaborate to strengthen the regula-tion of fatigued muscles.

Inguinal hernia is a common general surgical non-oncological condition,with more than 20 million inguinal hernia surgeries performed annually worldwide.Surgery is the only treatment for inguinal hernias in adults due to the lack of spontaneous healing and ineffective pharmacological treatment,as well as the risk of life-threatening intestinal necrosis due to herniorrhaphy.The incidence of inguinal hernia is on the rise,and there may be an association between its pathogenesis and the mechanism of sarcopenia,as well as the adverse effects of sarcopenia on various postoperative conditions.This paper aims to investigate the relationship between the recognition,diagnosis,treatment,pathogenesis,early postoperative clinical recovery and recurrence of sarcopenia in patients with inguinal hernia.

Heart failure （HF）， as the terminal stage of most cardiovascular diseases， manifests with primary symptoms including dyspnea， fatigue， edema， and palpitations. With recurrent episodes and a protracted clinical course， HF imposes a substantial global disease burden. PANoptosis represents a distinctive form of programmed cell death （PCD） that integrates features of pyroptosis， apoptosis， and necroptosis， yet cannot be fully attributed to any single pathway among these three PCD modalities. Recent studies demonstrate significant dysregulation of PANoptosis-related genes during HF progression， positioning PANoptosis as both an emerging mechanism mediating HF pathogenesis and a novel therapeutic target. In recent years， traditional Chinese medicine （TCM） has gained substantial recognition for its therapeutic potential in HF management， offering advantages such as flexible compatibility， multi-target effects， and minimal adverse reactions. Astragali Radix， a representative Qi-invigorating and blood-activating herbal medicine， has demonstrated remarkable clinical efficacy in the treatment for various HF subtypes. Research reveals that its major bioactive components—including astragaloside Ⅳ， polysaccharide， quercetin， and calycosin—exhibit significant associations with the regulation of apoptosis， pyroptosis， and necroptosis pathways. This review systematically explores the therapeutic feasibility of Astragali Radix in the prevention and treatment of HF through the lens of PANoptosis mechanisms. By synthesizing recent advances in the mechanisms of Astragali Radix-derived bioactive compounds and Astragali Radix-containing compound prescriptions in modulating PANoptosis， this paper aim to provide critical insights for advancing the diagnosis and therapeutic strategies of HF.