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.

ObjectiveUltra performance liquid chromatography-quadrupole-time of flight tandem mass spectrometry （UPLC-Q-TOF-MS/MS） coupled with network pharmacology and molecular docking was utilized to explore the efficacy and mechanism of action of Ermiao Situ decoction on rats with damp-heat eczema. MethodsA rat model of damp-heat eczema was established by artificial climate chamber intervention combined with sensitization induction by dinitrochlorobenzene （DNCB）， and it was randomly divided into the normal group， the model group， the medium- and high-dose groups of Ermiao Situ decoction （3.40 g·kg^-1 and 6.80 g·kg^-1）， and the prednisone acetate group （2.51 mg·kg^-1）， with eight rats in each group， totalling 46 rats， of which six rats were tested with the drug-containing serum. The chemical analysis of drug-containing serum from rats was carried out by UPLC-Q-TOF-MS/MS， combined with network pharmacology for the prediction of key components， core targets， and signaling pathways， and molecular docking experiments were performed by CB-Dock2 online website. The pharmacological effects of Ermiao Situ decoction in the treatment of damp-heat eczema were investigated by epitaxial indexes combined with the pathologic tissue staining method. The serum levels of gastrin （GAS）， interleukin-4 （IL-4）， and interleukin-13 （IL-13） were measured by enzyme-linked immunosorbent assay （ELISA）. Interleukin-6 （IL-6）， Janus kinase 1 （JAK1）， phosphorylated （p）-JAK1， signal transduction and activation of transcription factor 3 （STAT3）， and p-STAT3 protein expression level was determined by Western bolt. ResultsA total of 19 active ingredients were detected in drug-containing serum samples of rats， which were predicted to act on 198 targets for the treatment of damp-heat eczema， among which the key ingredients included rhodopsin， huangpai alkaloids， and quercetin， and the main core targets included STAT3， tumor necrosis factor （TNF）， and IL-6， which were mainly involved in the cancer signaling pathway， phosphatidylinositol 3-kinase （PI3K）/protein kinase （Akt） signaling pathway， T helper 17 （Th17） cell differentiation signaling pathway， and JAK/STAT signaling pathway. The molecular docking results suggested that the key components had strong binding activities with the core targets IL-6， JAK1， and STAT3 in the JAK/STAT signaling pathway. The results of animal experiments showed that compared with those in the normal group， rats in the model group were depressed. They had loose hair， loose stools， epidermal oozing， vesiculation， and generation of thick scabs in the form of scales， decreased body weight， increased anus temperature and water intake， and increased indexes of the spleen， thymus gland， and stomach （P<0.05， P<0.01）， and the lesion tissue could be seen to be hyperkeratotic， with the aggregation of inflammatory cells and nonsignificant separation of epidermis and dermis. The gastric mucosa was thinned， deficient， and structurally disorganized， and obvious inflammatory cell aggregation was seen. The levels of GAS， IL-4， and IL-13 in serum were significantly reduced （P<0.05， P<0.01）， and the protein expression levels of IL-6， JAK1， p-JAK1， and p-STAT3 in the lesion tissue were significantly increased （P<0.05， P<0.01）. Compared with those in the model group， rats in each administration group had stable mental states， formed feces， a clean perianal area， and basically normal epidermis. Only a small amount of scaly scabs existed， and the rats had body weight increased， with decreased anal temperature and water intake， as well as decreased spleen， thymus， and gastric indexes （P<0.05， P<0.01）. Epidermal thickness was decreased， and epidermal and dermal separation boundaries were obvious， but hyperkeratotic and accumulation of inflammatory cells could still be seen. The thickness of gastric mucosa increased， and the structure was restored to varying degrees. The levels of GAS， IL-4， and IL-13 content in the serum of rats were increased to varying degrees， and the protein expression levels of IL-6， JAK1， p-JAK1， and p-STAT3 in the dermal lesion tissue were significantly decreased （P<0.05， P<0.01）. ConclusionErmiao Situ decoction may exert therapeutic effects on rats with damp-heat eczema by modulating the JAK/STAT signaling pathway.

OBJECTIVE To investigate the antidepressant mechanism of Shugan hewei tang （SGHWT） based on the metabolomics of prefrontal cortex （PFC）-nucleus accumbens （NAc）-ventral tegmental area （VTA） neural circuit. METHODS Male SD rats were randomly divided into blank group， model group， SGHWT low-， medium- and high-dose groups [3.67， 7.34， 14.68 g/（kg·d）， by raw material]， and fluoxetine group [1.58 mg/（kg·d）， positive control]， with 12 rats in each group. Except for the blank group， the depression model was established by chronic unpredictable mild stress combined with individual cage housing in the remaining groups， and the corresponding drug solution or normal saline was administered via gavage during modeling， once a day， for 6 consecutive weeks. After the last administration， the body weight， sucrose preference rate， total moving distance， frequency into the center and immobility time of rats in each group were detected. Samples of PFC， NAc and VTA areas of rats in the blank group， model group， SGHWT medium-dose group and fluoxetine positive control groups were collected，and their histomorphological features were observed， and non-targeted metabolomics analysis （except for fluoxetine group）were performed and validated. RESULTS Compared with model group， the cytolysis， structural damage and other pathological damages in three brain regions of rats were significantly alleviated in each drug group， while their body weight， sucrose preference rate， total moving distance and frequency into the center were all significantly higher or longer （P＜0.05）， and immobility time was significantly shorter （P＜0.05）. The results of non-targeted metabolomics showed that a total of 78 endogenous differential metabolites were identified， with 40， 35 and 24 in the PFC， NAc and VTA regions respectively， mainly involved in amino acid， lipid and sphingolipid metabolism. The results of metabolic pathway enrichment analysis showed that SGHWT affected the neural circuits of depressed rats by regulating sphingolipid metabolism， alanine， aspartic acid and glutamic acid metabolism， saturated fatty acid biosynthesis， among which alanine， aspartic acid and glutamic acid metabolism was predominantly involved. Validation experiments showed that SGHWT significantly increased the phosphorylation levels of protein kinase B （Akt） and mammalian target of rapamycin （mTOR）， and decreased the protein expression of N-methyl-D-aspartic acid receptor 1 （NMDAR1） in the NAc region of rats. CONCLUSIONS SGHWT significantly improves the depression-like behavior and attenuates pathological damage of PFC-NAc-VTA neural circuit of model rats， the mechanism of which is associated with inhibiting NMDAR1 expression and activating the Akt/mTOR signaling pathway.

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.

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.

Objective:To explore the impacts of acupuncture and moxibustion combined with ABCLOVE voice training on voice function and the levels of inflammatory factors in patients who were diagnosed with vocal cord polyp and received operation. Methods:A total of 96 cases who received operation on vocal cord polyp were randomly assigned into two groups. The control group was given ABCLOVE voice training for rehabilitation after the operation. The study group was given acupuncture and moxibustion combined with ABCLOVE voice training. The voice function and the levels of inflammatory factors of the two groups were compared. Results:The effective rate of the study group was higher than that of the control group（P<0.05）. The scores of main symptoms such as hoarseness, dry mouth, and thirst in the study group were lower than those in the control group（P<0.05）. After 4 weeks of treatment, the voice fundamental frequency（F0） of the study group was higher than that of the control group（P<0.05）, the maximum phonation time（MPT） was longer than that of the control group（P<0.05）, and the voice fundamental frequency perturbation value（Jitter） and voice amplitude perturbation value（Shimmer） were lower than those of the control group（P<0.05）. The levels of serum interleukin-6（IL-6） and tumor necrosis factor-α（TNF-α） were lower than those of the control group（P<0.05）. Conclusion:Acupuncture and moxibustion combined with ABCLOVE voice training can obviously alleviate hoarseness and other symptoms, improve voice function and reduce the level of inflammatory factors, thus is an effective treatment for patients who received operation on vocal cord polyp.
Humans ; Moxibustion ; Polyps/therapy* ; Vocal Cords ; Acupuncture Therapy ; Voice Training ; Female ; Male ; Adult ; Middle Aged ; Interleukin-6/blood* ; Tumor Necrosis Factor-alpha/blood* ; Young Adult ; Laryngeal Diseases/therapy*

The regulatory processes in developmental biology research are significantly influenced by long non-coding RNAs (lncRNAs). However, the dynamics of lncRNA expression during human tooth development remain poorly understood. In this research, we examined the lncRNAs present in the dental epithelium (DE) and dental mesenchyme (DM) at the late bud, cap, and early bell stages of human fetal tooth development through bulk RNA sequencing. Developmental regulators co-expressed with neighboring lncRNAs were significantly enriched in odontogenesis. Specific lncRNAs expressed in the DE and DM, such as PANCR, MIR205HG, DLX6-AS1, and DNM3OS, were identified through a combination of bulk RNA sequencing and single-cell analysis. Further subcluster analysis revealed lncRNAs specifically expressed in important regions of the tooth germ, such as the inner enamel epithelium and coronal dental papilla (CDP). Functionally, we demonstrated that CDP-specific DLX6-AS1 enhanced odontoblastic differentiation in human tooth germ mesenchymal cells and dental pulp stem cells. These findings suggest that lncRNAs could serve as valuable cell markers for tooth development and potential therapeutic targets for tooth regeneration.
Humans ; RNA, Long Noncoding/metabolism* ; Odontogenesis/genetics* ; Tooth Germ/embryology* ; Cell Differentiation ; Gene Expression Regulation, Developmental ; Mesoderm/metabolism* ; Tooth/embryology* ; Gene Expression Profiling ; Sequence Analysis, RNA ; Dental Pulp/cytology*

Objective: To establish and validate a whole blood (WB) supply model, thereby providing practical experience for the clinical application of WB in domestic trauma emergency care and informing the development of a wartime blood supply system for the military. Methods: A “10×24” WB supply model was established by formulating blood collection protocols, storage standards, and transfusion criteria. Multiple WB samples were tested under specific storage conditions to assess key indicators at different time points, including red blood cell (RBC), white blood cell (WBC), and platelet counts, hemoglobin concentration, coagulation parameters (PT, APTT, TT, FIB), coagulation factor activity, thromboelastography (TEG) parameters, and electrolyte levels. Additionally, clinical data from hemorrhagic patients who met the criteria for WB transfusion and were admitted between March and July 2024 were analyzed to evaluate WB transfusion volume. Results: RBC counts and hemoglobin levels remained stable in WB stored at 4℃ for up to 10 days. However, platelet counts and coagulation function (PT, APTT) significantly declined with prolonged storage, while potassium levels increased. From March to July 2024, the model was successfully applied to 23 patients with acute hemorrhage, with a median WB transfusion volume of 543 mL. A detailed case study of a severe traumatic hemorrhagic shock patient was reported, who was successfully treated with 5.5 units of refrigerated WB combined with component blood. Conclusion: The “10×24” WB supply model demonstrated acceptable changes in critical quality parameters under strict management and a 10-day rotation cycle. This model effectively supports the treatment of acute hemorrhage and holds promise for integration into the future wartime blood supply system of the military.

Objective:To observe the expression of T cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domain(TIGIT)in tumor tissue and peripheral blood CD8+T cells in patients with triple-negative breast cancer(TNBC),and to explore the ef-fect of tiragolumab on the function of CD8+T cells in the peripheral blood of these patients.Methods:The expression of TIGIT in tumor tissue of patients with TNBC was analyzed using The Cancer Genome Atlas(TCGA)database and immunohistochemical staining.Flow cytometry was employed to assess the co-expression of TIGIT and programmed death-1(PD-1)in peripheral blood CD8+T cells,as well as their cytokine secretion.A co-culture model of CD8+T cells and TNBC cell lines,HCC-1937 and MDA-MB-231,was estab-lished.The effect of tiragolumab on the anti-tumor activity of CD8+T cells in patients with TNBC was investigated using flow cytometry and confocal fluorescence imaging.Results:The expression of TIGIT in tumor tissue and peripheral blood CD8+T cells of patients with TNBC was significantly increased(P<0.05).Compared with the healthy control group,the TNBC group showed a significantly larger number of TIGIT+PD-1+CD8+T cells in the peripheral blood and significantly reduced secretion of interferon gamma(IFN-γ),tumor necrosis factor-α(TNF-α),and ginkgolide B(GB)by CD8+T cells;specifically,TIGIT+CD8+T cells demonstrated significantly re-duced secretion compared with TIGIT-CD8+T cells(P<0.05).Fol-lowing treatment with tiragolumab,TIGIT+CD8+T cells exhibited increased secretion of IFN-γ and TNF-α(P<0.05).In the co-culture model,tiragolumab restored the apoptosis-inducing ability of CD8+T cells in patients with TNBC,and this ability was further enhanced when it was combined with envafolimab.Conclusion:Ti-ragolumab restores the tumor-killing function of CD8+T cells by im-proving their immunosuppression.The combination of tiragolumab with envafolimab can further enhance its anti-tumor effect.

Acupuncture treatment of chronic pain combined with depression (CPDC) is the result of a multi-target, multi-pathway approach. Acupuncture can treat CPDC by inhibiting the activation of glial cells, regulating the release of inflammatory mediators, regulating the expressions of neurotransmitters, changing the plasticity of neural synapses, regulating related epigenetic effects, regulating the microbiota-brain-gut axis, inhibiting nerve cell apoptosis, and antagonizing oxidative stress. The mechanism of its effect mainly involves anti-inflammatory related signaling pathways, regulation of neural synapse-related signaling pathways, and exerts its therapeutic effect through hippocampus, cerebral cortex, and amygdala.