BACKGROUND:Hydroxy safflower yellow A has anti-ischemia,anti-oxidation,anti-thrombotic and anti-inflammatory effects.Whether it affects neuronal pyroptosis after glucose-oxygen deprivation/reglucose-reoxygenation is still unclear. OBJECTIVE:To investigate the protective effect of hydroxy safflower yellow A on neuronal pyroptosis and its mechanism. METHODS:HT22 cells in logarithmic growth phase were randomly divided into five groups:normal group,model group,hydroxy safflower yellow A group,colivelin group,and colivelin+hydroxy safflower yellow A group.HT22 cells were treated with glucose-oxygen deprivation/reglucose-reoxygenation to establish neuronal pyroptosis model,and then treated with STAT3 agonist Colivelin and hydroxy safflower yellow A.JC-1 probe was employed to assess changes in mitochondrial membrane potential.Reactive oxygen species kit was used to determine the content of reactive oxygen species in cells.GSDMD/TUNEL staining was conducted to observe cell pyroptosis.Immunofluorescence analysis was performed to detect STAT3 and GSDMD protein expression.RT-PCR was utilized for assessing mRNA expression levels of STAT3,NLRP3,and Caspase-1.Western blot assay was utilized to measure the protein expression levels of p-STAT3,NLRP3,GSDMD,Cleaved-caspase-1,and interleukin-1β. RESULTS AND CONCLUSION:(1)Compared with the normal group,the number of pyroptotic cells increased in HT22 cells in the model group along with a significant increase in protein expression levels of p-STAT3,NLRP3,Cleaved-caspase-1,GSDMD,and interleukin-1β.Compared with the model group,the number of pyroptotic cells reduced,and the expression of pyroptosis-related proteins significantly decreased in the hydroxy safflower yellow A group.(2)In comparison with the model group,pyroptosis worsened in the colivelin group where mitochondrial membrane potential decreased along with elevated reactive oxygen species content and increased mRNA expression levels of STAT3,NLRP3,and Caspase-1,as well as increased protein expression levels of p-STAT3,NLRP3,GSDMD,Cleaved-caspase-1,and interleukin-1β.Compared with the Colivelin group,above indexes were improved in the colivelin+hydroxy safflower yellow A group.These results suggest that hydroxy safflower yellow A plays a neuroprotective role through STAT3 signaling pathway to inhibit HT22 pyroptosis after glucose-oxygen deprivation/reglucose-reoxygenation treatment.

ObjectiveTo investigate the effect and mechanism of Bukan Yilidan on perimenopausal psycho-cardiac disease by mitochondrial autophagy mediated by dynamin-related protein 1（Drp1）/phosphatase and tensin homolog（PTEN） induced putative kinase 1（PINK1）/Parkin pathway. MethodsSixty rats were randomly divided into the blank group， model group， western medicine group（isosorbide mononitrate 7.2 mg·kg^-1+sertraline hydrochloride tablets 18 mg·kg^-1）， Bukan Yilidan low， medium and high dose groups（2.59， 5.18， 10.35 g·kg^-1）， with 10 rats in each group. Except for the blank group， the rat model of perimenopausal psycho-cardiac disease was prepared by ovariectomy（OVX） combined with high-fat feeding， chronic unpredictable mild stress（CUMS） and subcutaneous multi-point injection of isoproterenol hydrochloride. After successful modeling， the general state and tongue image of rats were observed. The depression status of rats in vivo was evaluated by open field test， sucrose preference test， forced swimming immobility time and grip strength value， and the cardiac function of rats was evaluated by electrocardiogram and echocardiography. The levels of serum norepinephrine（NE）， dopamine（DA） and 5-hydroxytryptamine（5-HT） were detected by enzyme-linked immunosorbent assay（ELISA）， and biochemical detection was used to assess myocardial injury by measuring serum levels of high-density lipoprotein cholesterol（HDL-C）， low-density lipoprotein cholesterol（LDL-C）， triglyceride（TG）， total cholesterol（TC）， aspartate aminotransferase（AST）， alanine aminotransferase（ALT）， lactate dehydrogenase（LDH） and creatine kinase isoenzyme（CK-MB）. Hematoxylin-eosin（HE） and Nissl staining were used to observe the pathological status of hippocampus and myocardial tissue in rats， the status of mitophagosomes in hippocampus and myocardium was observed by transmission electron microscope（TEM）， and Western blot was used to detect the contents of Drp1， mitochondrial fusion protein 2（Mfn2）， optic atrophy protein 1（OPA1）， PINK1， Parkin， p62 and microtubule-associated protein light chain 3B（LC3B） in hippocampus and myocardium. ResultsCompared with the blank group， the food intake and water intake of rats in the model group decreased， the hair was dark yellow， the gloss and smoothness decreased， the spirit was depressed， the tongue was light purple or dark purple， accompanied by petechiae or ecchymosis， the sublingual collaterals were purple and black， and the tongue coating was white and smooth. The indexes of open field test， grip strength and sucrose preference of rats decreased significantly， and the immobility time of forced swimming increased significantly（P<0.01）. Electrocardiogram and echocardiography showed that ST segment was significantly depressed， and left ventricular fractional shortening（LVFS） and left ventricular ejection fraction（LVEF） were significantly decreased（P<0.05， P<0.01）. Pathological observation showed that the number of hippocampal neurons and myocardial cells decreased， and the structural damage was obvious. The levels of serum TC， TG， LDL-C， CK-MB， LDH， AST and ALT increased， while the levels of HDL-C， 5-HT， DA and NE decreased（P<0.05， P<0.01）. TEM showed obvious mitochondrial damage in hippocampus and myocardial tissue. The protein expressions of Drp1， PINK1， Parkin and p62 in hippocampus and myocardium were increased， while the protein expressions of OPA1， Mfn2 and LC3BⅡ/Ⅰ were decreased（P<0.05， P<0.01）. Compared with the model group， the mental state， body curling up， fear of cold and other symptoms of rats in each administration group were improved， and the degree of pale purple or dark purple tongue was reduced. The scores of open field test， grip strength， sucrose preference， LVFS and LVEF were increased， and the immobility time of forced swimming was shortened（P<0.05， P<0.01）. The ST segment of electrocardiogram had a significant recovery（P<0.01）， pathological observation showed that the damage of nerve cells and myocardial tissue was improved. The levels of serum TC， TG， LDL-C， CK-MB， LDH， AST and ALT decreased， while the levels of HDL-C， 5-HT， DA and NE increased（P<0.05， P<0.01）. TEM showed that mitochondrial damage was reduced in hippocampal neurons and cardiomyocytes with visible mitochondrial autophagosomes. The protein expressions of Drp1， PINK1， Parkin and p62 in hippocampus and myocardium were decreased， while the protein expressions of OPA1， Mfn2 and LC3BⅡ/Ⅰ were increased（P<0.05， P<0.01）. ConclusionBukan Yilidan can alleviate depression， lipid metabolism disorder and myocardial ischemia injury in rats with perimenopausal psycho-cardiac disease， and its mechanism may be related to inhibiting Drp1/PINK1/Parkin signaling pathway and enhancing mitochondrial autophagy.

OBJECTIVE To analyze the components migrating to blood and metabolites of Polygonum cuspidatum in rats with acute gouty arthritis （AGA）. METHODS SD rats were randomly divided into blank group， model group and P. cuspidatum group （10 g/kg， by raw material）， with 6 rats in each group. Except for blank group， AGA model was induced in the remaining groups by injecting potassium oxonate and sodium urate； meanwhile， they were administered corresponding drug solutions or water intragastrically， once a day， for 10 consecutive days. The histopathological morphology of the knee joint tissues in rats was observed；rat serum samples were collected， and the components migrating to blood and metabolites of P. cuspidatum were analyzed by using UPLC-Q-Exactive-Orbitrap-MS. RESULTS Following the intervention with P. cuspidatum， the histopathological morphology of the knee joint synovial tissue in AGA rats showed significant improvement， with reduced inflammatory cell infiltration and hyperplasia， and the preservation of the honeycomb-like structure integrity. In both positive and negative ion modes， a total of 67 chemical components were detected in the serum of rats from P. cuspidatum group， including 25 prototype components and 42 metabolites. The involved compound types encompassed stilbenes， anthraquinones， naphthols， and flavonoids， among others. The metabolic reactions identified included methylation， acetylation， sulfation， and glucuronidation. Notably， compounds such as polydatin， resveratrol and emodin were capable of entering the bloodstream in their prototype forms and undergoing in vivo metabolism. CONCLUSIONS Compounds such as polydatin， resveratrol and emodin are likely to be the active components responsible for the anti-AGA effects of P. cuspidatum.

Under the background of the Healthy China strategy， the integration of traditional Chinese medicine （TCM） into the public health emergency response system has become an important measure to enhance the capacity for coping with public health emergencies. In recent years， the role of TCM in responding to such emergencies has become increasingly prominent. Taking major emerging epidemics as an example， TCM has developed a rich theoretical system and practical experience in epidemic prevention and treatment over thousands of years， and has played a significant role in successive outbreaks with its unique advantages. Based on the concept of ''preventing disease before its onset'' and the theoretical framework of treatment based on syndrome differentiation， TCM has achieved remarkable results through early intervention and full participation in the integrated model of TCM and Western medicine， from severe acute respiratory syndrome （SARS） to corona virus disease-2019 （COVID-19）， in improving clinical symptoms and outcomes， reducing adverse reactions， and promoting recovery. From the perspective of the Healthy China strategy， this paper systematically reviews the historical development of TCM in epidemic prevention and treatment， with particular attention to recent epidemics such as SARS， influenza A （H1N1）， and COVID-19. It further examines the similarities and differences between TCM and Western medicine in responding to major emerging epidemics， as well as relevant policies related to TCM in epidemic prevention and control. In addition， it summarizes the existing problems in TCM's role in the prevention and treatment of major emerging epidemics， and explores measures to improve its rapid response capacity under the Healthy China strategy. This study not only provides a ''Chinese solution'' for the prevention and control of newly emerging infectious diseases worldwide， but also offers theoretical and practical references for strengthening the public health emergency response system， carrying strategic significance for promoting the modernization and internationalization of TCM.

Autophagy is a fundamental biological metabolic process involved in immune defense, material metabolism, and homeostasis and closely linked to immune regulation. Systemic lupus erythematosus (SLE) is a widespread connective tissue disorder primarily resulting from immune system imbalance. Due to the immune system's failure to recognize its own substances, it generates autoantibodies that can affect various tissues and organs, leading to diverse clinical manifestations. The pathogenesis and treatment of SLE are currently under extensive investigation. In normal metabolic processes, autophagy engages in both innate and adaptive immunity, regulates the immune response, and is crucial for maintaining normal immune function and the body's internal homeostasis. Research has indicated that SLE patients exhibit immune dysfunction and altered autophagy levels. Modulating autophagy expression can influence immune system functionality and alleviate SLE symptoms. Additionally, autophagy aids in the innate immune response and adaptive immunity by clearing metabolites and regulating the life cycle of immune cells. Studies suggest that drugs targeting autophagy can positively influence the progression of SLE. This article reviews advancements in research regarding the impact of autophagy on the pathogenesis of SLE through the regulation of immune system functions.
Lupus Erythematosus, Systemic/pathology* ; Autophagy/immunology* ; Humans ; Animals ; Immunity, Innate ; Adaptive Immunity ; Disease Progression ; Immune System/immunology*

Foot-and-mouth disease (FMD) is one of the major animal infectious diseases in the world. All cloven-hoofed animals are susceptible to FMD. Vaccination is still the first choice for the prevention and control of FMD. mRNA vaccines can be rapidly designed, synthesized, and produced on a large scale in vitro, and they can induce effective protective immune responses, demonstrating the advantages of rapid development, easy preparation, and low biosafety risks. The design of untranslated regions is a key to enhancing the expression and efficacy of mRNA vaccines. In order to generate an efficient FMD mRNA vaccine, we designed three FMD P12A3C expression vectors with different untranslated regions and synthesized corresponding mRNAs. By comparing expression efficiency of these vectors and their mRNAs at different time points and in different cell lines, we found that the mRNA P12A3C-UTR3 had the best expression and universality. This study laid a foundation for the development of mRNA vaccines against FMD and provided a theoretical basis for the optimal sequence design of efficient mRNA.
Foot-and-Mouth Disease Virus/genetics* ; Animals ; RNA, Messenger/biosynthesis* ; Foot-and-Mouth Disease/immunology* ; Antigens, Viral/biosynthesis* ; Viral Vaccines/biosynthesis* ; Genetic Vectors/genetics* ; Cell Line ; Vaccines, DNA/immunology*

Genetically modified (GM) crops, as a pivotal innovation in modern agriculture, exhibit significant advantages such as pest and disease resistance, herbicide tolerance, stress tolerance, and yield enhancement. However, their widespread adoption has been associated with potential ecological risks, including weediness of transgenic plants, gene flow, emergence of novel viral strains in virus-resistant crops, impacts on non-target organisms and soil ecosystems, and evolution of target pest resistance. This review focuses on the dual characteristics of GM crops, systematically examining their agronomic benefits and the underlying mechanisms of ecological risks. This review provides a theoretical foundation for optimizing the development of GM crops and ecological risk management, facilitating sustainable agricultural practices.
Plants, Genetically Modified/growth & development* ; Crops, Agricultural/growth & development* ; Ecosystem ; Ecology

Objective:To analyze the clinicopathological features and differential diagnosis of large B-cell lymphoma with IRF4 rearrangement, aiming enhance its recognition and prevent misdiagnosis.Methods:The clinicopathological features, immunophenotype, and fluorescence in situ hybridization (FISH) results of six cases diagnosed with IRF4 rearrangement-positive B-cell lymphoma at the Affiliated Hospital of Xuzhou Medical University from 2015 to 2023 were retrospectively analyzed. Additionally, a comprehensive review of the literature was conducted.Results:Six patients with IRF4 rearrangement-positive large B-cell lymphoma were included. Patients 1 to 5 included three males and two females with a median age of 19 years ranging from 11 to 34 years. Four patients presented with head and neck lesions, while the other one had a breast nodule; all were in clinical Ann Arbor stages I to Ⅱ. Morphologically, entirely diffuse pattern was present in two cases, purely follicular pattern in one case, and diffuse and follicular patterns in other two cases. The tumor cells, predominantly centroblasts mixed with some irregular centrocytes, were of medium to large size, with a starry sky appearance observed in two cases. Immunophenotyping revealed all cases were positive for bcl-6 and MUM1, with a Ki-67 index ranging from 70% to 90%, and CD10 was positive in two cases. IRF4 rearrangement was confirmed in all cases by FISH analysis, with dual IRF4/bcl-6 rearrangements identified in two cases, leading to a diagnosis of LBCL-IRF4. Case 6, a 39-year-old female with a tonsillar mass and classified as clinical Ann Arbor stage Ⅳ, displayed predominantly diffuse large B-cell lymphoma (DLBCL) morphology with 20% high-grade follicular lymphoma characteristics. Immunohistochemistry showed negative CD10 and positive bcl-6/MUM1, with a Ki-67 index of approximately 80%. Triple rearrangements of IRF4/bcl-2/bcl-6 were identified by FISH, leading to a diagnosis of DLBCL with 20% follicular lymphoma (FL). All six patients achieved complete remission after treatment, with no progression or relapse during a follow-up period of 31-100 months.Conclusions:Large B-cell lymphoma with IRF4 rearrangement is a rare entity with pathological features that overlap with those of FL and DLBCL. While IRF4 rearrangement is necessary for diagnosing LBCL-IRF4, it is not specific and requires differentiation from other aggressive B-cell lymphomas with IRF4 rearrangement.

AIM:To investigate the effects of cannabinoid receptor agonist WIN55212-2(WIN)on acute lung injury(ALI)in septic mice,and to explore its potential mechanisms through glycolysis.METHODS:A mouse model of septic ALI was established by intraperitoneal injections of lipopolysaccharide(LPS).Male C57BL/6J mice were randomly divided into 4 groups(n=6):(1)control group;(2)LPS group,receiving intraperitoneal injections of LPS at 10 mg/kg;(3)LPS+WIN group,receiving 1 mg/kg WIN intraperitoneally 30 min prior to LPS injection;(4)LPS+WIN+MHY1485[mammalian target of rapamycin(mTOR)activator]group,receiving 10 mg/kg MHY1485 intraperitoneally 1 d before LPS injection and 1 mg/kg WIN plus 10 mg/kg MHY1485 30 min before LPS injection.Tissues were collected 24 h after modeling for analysis.Lung indexes were calculated,and histopathological changes of lung tissues were observed via he-matoxylin-eosin(HE)staining.Inflammatory cytokines interleukin-1β(IL-1β)and IL-10 in lung tissues,and lactic acid and lactate dehydrogenase A(LDHA)in serum were quantified using ELISA.The levels of mTOR/hypoxia-inducible fac-tor-1α(HIF-1α)/6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3(PFKFB3)signaling pathway-related proteins were assessed by Western blot.RESULTS:Compared with control group,the LPS group exhibited an increased lung in-dex,significant lung tissue damage,an increase in IL-1β levels(P＜0.05),a decrease in IL-10 levels(P＜0.05),and el-evated expressions of lactate and LDHA(P＜0.05),along with increased levels of phosphorylated mTOR(p-mTOR),HIF-1α and PFKFB3 proteins(P＜0.05).The LPS+WIN group showed improvements with a reduced lung index(P＜0.05),lessened lung injury,decreased IL-1β levels(P＜0.05),increased IL-10 levels(P＜0.05),and lower levels of lactic acid,LDHA,p-mTOR,HIF-1α,and PFKFB3(P＜0.05).Conversely,the LPS+WIN+MHY1485 group displayed increased lung indexes and lung tissue damage,elevated IL-1β levels(P＜0.05),reduced IL-10 levels(P＜0.05),and higher expressions of lactic acid,LDHA,p-mTOR,HIF-1α and PFKFB3(P＜0.05)compared to the LPS+WIN group.CONCLUSION:WIN55212-2 mitigates sepsis-induced ALI,potentially by modulating the mTOR/HIF-1α/PFKFB3 sig-naling pathway,thereby inhibiting glycolysis and alleviating inflammatory responses.

Objective To observe the value of augmented reality(AR)navigation system for assisting CT-guided puncture of pulmonary nodules in dog models.Methods Five healthy dogs were selected,and 4 target lung rings were implanted in each dog to build pulmonary nodule models.Deferring to crossover design,CT-guided punctures were performed with or without AR navigation 2 and 4 weeks after successful modeling,respectively,while punctures with AR navigation were regarded as AR group and the others as conventional group,respectively.The time duration of puncturing,the times of CT scanning,of needle adjustment,and the deviation distance between needle pinpoint to the center of pulmonary nodule shown on three-dimensional reconstruction were compared between groups.Results The duration time of puncture in AR group and conventional group was(13.62±5.11)min and(20.16±4.76)min,respectively.In AR group,the times of CT scanning,of needle adjustment,and the deviation distance was 2.40±0.50,2.75±0.44 and(2.94±1.92)mm,respectively,while in conventional group was 3.10±0.64,3.70±0.57 and(4.90±3.38)mm,respectively.The introduction of AR navigation was helpful to shortening the duration of puncture,reducing times of CT scanning and needle adjustment,also decreasing positioning error of needle pinpoint(all P＜0.05).In contrast,the variance of puncture sequences and dogs had no obvious effect on the results(both P＞0.05).Conclusion AR navigation system could improve accuracy and efficiency in CT-guided puncture of pulmonary nodules in dog models.