Abstract: Objective To investigate the neuroprotective effect of remote ischemic preconditioning (RIPC) against hypoxic ischemia through decreased neuronal DNA methyltransferase (DNMT) levels via plasma exosomes. Methods C57BL / 6J mice were subjected to RIPC with the simultaneous tail vein injection of the exosome inhibitor GW4869; after 1 hour, middle cerebral artery occlusion (MCAO) was performed. Mice were randomized into four groups. Bederson scores and cornering tests were used to assess the degree of neurologic impairment. Expression levels of DNA methyltransferases ( DNMTs) and nerve damage-related genes in the mouse cerebral cortex were evaluated using RT-qPCR and Western blot. Plasma exosomes were extracted from mice before and after RIPC and cocultured with mouse neuronal cells (HT22) for oxygen glucose deprivation (OGD). Cell viability was assessed using CCK8 assays. The cell morphology and fluorescence intensity of the anti-apoptotic protein Bcl-2 were observed through immunofluorescence, and the mRNA and protein expression levels of DNMTs and apoptotic genes (Caspase3, BAX,and Bcl-2) were detected. Results Bederson scores and cornering experiments showed that RIPC intervention improved neurological deficits significantly after MCAO in mice, and its neuroprotective effect was significantly attenuated after the administration of GW4869(P<0. 05). RIPC treatment down-regulated DNMTs, Caspase3, and BAX and up-regulated Bcl-2 in the cerebral cortex of MCAO mice(P<0. 05). In vitro assays showed that RIPCderived exosomes reduce DNMT expression, increase the fluorescence intensity of Bcl-2, and improve cell morphology in HT22 cells under OGD conditions, while down-regulating Caspase3 and BAX and increasing cell viability ( P<0. 05). Conclusions RIPC may exert a neuroprotective effect by downregulating DNMTs in a plasma exosomemediated manner, inhibiting Caspase3 and BAX expression, increasing Bcl-2 expression, inhibiting neuronal apoptosis, and increasing the tolerance of neuronal cells to the hypoxic-ischemic environment.

Abstract: Objective To investigate the beneficial effects of catalpol-paeoniflorin ( CTP-PNF ) on perimenopausal depression (PMD) and to explore its underlying mechanism, specifically focusing on its ability to inhibit miR-124-to promote the proliferation and migration of neural stem cells. Methods A PMD mouse model was established, combined with intracerebral stereotaxic microinjection of miR-124 inhibitor and in vitro neural stem cell experiments. Depressive-like behaviors were evaluated using the sucrose preference test (SPT), tail suspension test (TST), and novelty-suppressed feeding test (NSFT). Relative expression levels of miR-124 in the prefrontal cortex of mice were detected by quantitative reverse transcription-polymerase chain reaction and levels of the neurotransmitters norepinephrine, dopamine, serotonin, and gamma-aminobutyric acid were measured by enzyme-linked immunosorbent assay. Neuronal pathological changes were observed by Nissl staining. The viability and migration ability of neural stem cells were detected by MTT and Transwell assays, respectively. The core targets and pathways involved in miR-124-mediated intervention of PMD by CTP-PNF were analyzed by network pharmacology. Results Compared with the model group, CTP-PNF significantly improved depressive-like behaviors in PMD mice and downregulated the expression of miR-124 in the prefrontal cortex (P<0. 001). Inhibition of miR-124 reduced depressive-like behaviors, increased neurotransmitter levels ( P< 0. 05 ), ameliorated the pathological status of the prefrontal cortex and hippocampus, and synergistically enhanced the viability and migration of neural stem cells with CTP-PNF-containing serum, thereby promoting neural stem cell repair. Comprehensive bioinformatics analysis based on network pharmacology revealed that miR-124-mediated treatment of PMD by CTP-PNF mainly involved 56 core therapeutic targets, including the hypoxia-inducible factor 1 signaling pathway, 5-HT signaling pathway, and cAMP signaling pathway related to mitogen-activated protein kinase 1, signal transducer and activator of transcription 3, TP53, and vascular endothelial growth factor A. Conclusions CTP-PNF significantly ameliorates depressive-like behaviors and neuropathological damage in PMD mice by downregulating miR-124 to promote the proliferation and migration of neural stem cells and regulate neurotransmitter networks. Its mechanism involves multiple signaling pathways, including hypoxia-inducible factor 1 and 5-HT. CTP-PNF may thus provide a new traditional Chinese medicine intervention strategy and molecular target for the treatment of PMD.

Abstract: Objective To investigate the protective effects and mechanisms of hawthorn total flavonoids against myocardial ischemia-reperfusion (I/ R) injury in rats via the HIF-1 signaling pathway. Methods An ex vivo rat heart I/ R model was established. Animals were randomized into five groups: Sham, I/ R, low-dose hawthorn total flavonoids (HTF-L), high-dose hawthorn total flavonoids (HTF-H), and HTF-H combined with the PI3K inhibitor LY294002(HTF-H+LY). Cardiac function (LVSP, LVEDP, and ±dp / dt_max), myocardial apoptosis (TUNEL),oxidative stress markers (SOD and MDA), and protein expression of HIF-1α and upstream pathways (PI3K/ Akt and MAPK) were assessed after 60 min of reperfusion. Results Compared with the Sham group, the I/ R group exhibited significantly decreased cardiac function ( LVSP and ± dp / dt _ max, both P<0. 01), and increased apoptosis and oxidative stress levels (both P<0. 01). HTF treatment significantly improved cardiac function (P<0. 05 or P<0. 01),suppressed apoptosis and oxidative stress (P<0. 05 or P<0. 01) in a dose-dependent manner. Western blot showed that HTF significantly upregulated HIF-1α and upstream PI3K/ Akt / MAPK signaling pathway proteins (P<0. 05 or P<0. 01). PI3K inhibition partially reversed the protective effects of HTF (P<0. 05). Conclusions Hawthorn total flavonoids can alleviate myocardial injury induced by ischemia / reperfusion (I/ R) via activation of the HIF-1 signaling pathway; the underlying mechanism involves inhibition of cardiomyocyte apoptosis and oxidative stress. These findings provide experimental evidence for both the application of hawthorn as a food-medicine homologous agent in the prevention and treatment of cardiovascular diseases and for research into its molecular mechanisms.

Abstract: Objective To discuss the effects of geniposide on proliferation, apoptosis, and autophagy in lung cancer cells by regulating the adenosine monophosphate-activated protein kinase (AMPK) / mammalian target of rapamycin (mTOR) / unc-51 like kinase 1 (ULK1) pathway. Methods A549 cells were divided into lung cancer,low-dose geniposide, medium-dose geniposide, high-dose geniposide, AMPK activator (MK8722), and high-dose geniposide+AMPK inhibitor (Compound C) groups. 5-Ethynyl-2’ deoxyuridine (EdU) staining and CCK-8 assays were used to detect cell proliferation. Flow cytometry was used to detect cell apoptosis. Transmission electron microscopy was used to count autophagosomes in A549 cells. RT-qPCR was used to detect the mRNA expression of proliferating cell nuclear antigen ( PCNA), p53, p62, and Bcl-2 homologous domain protein ( Beclin1) in A549 cells. Western blot was used to detect microtubule associated protein 1 light chain 3 (LC3), p-AMPK, p-mTOR, and p-ULK1 in A549 cells. Results Compared with levels in the lung cancer group, the low-, medium-, and high-dose geniposide groups showed decreases in the EdU-positive rate, OD₄₅₀ value, PCNA and p62 mRNA levels, and pmTOR protein expression in A549 cells and increases in the apoptosis rate, autophagosome number, p53 and Beclin1 mRNA levels, and LC3-II/ LC3-I, p-AMPK, and p-ULK1 protein levels; the high-dose geniposide group showed the most prominent differences (P<0. 05). Compared with levels in the lung cancer group, the MK8722 group showed decreases in the EdU-positive rate, OD₄₅₀ value, PCNA and p62 mRNA levels, and p-mTOR protein expression in A549 cells and increases in the apoptosis rate, autophagosome number, p53 and Beclin1 mRNA levels(P<0. 05), and LC3-II/ LC3-I, p-AMPK, and p-ULK1 protein levels ( P< 0. 05). Compared with levels in the high-dose geniposide group, the high-dose geniposide+Compound C group showed increases in the EdU-positive rate, OD₄₅₀ value, PCNA and p62 mRNA levels, and p-mTOR protein levels in A549 cells and decreases in the apoptosis rate,autophagosome number, p53 and Beclin1 mRNA levels ( P< 0. 05), and LC3-II/ LC3-I, p-AMPK, and p-ULK1 protein levels (P<0. 05). Conclusions Geniposide may inhibit A549 cell proliferation and promote autophagy and apoptosis through activating the AMPK/ mTOR/ ULK1 pathway.

Abstract: Objective To investigate and compare the protective effects of three classic Mongolian medicines, Danggong-3 (DG-3), Zandan-3 (ZD-3), and Zadi-5 (ZD-5), on myocardial ischemia-reperfusion injury (MIRI) in mice. Methods Seven-week-old male C57BL / 6 mice were divided randomly into six groups: sham operation, model, compound Danshen dropping pills (positive control), DG-3, ZD-3, and ZD-5 groups. The mice were administered drugs by gavage 14 days before modeling. The model was established using the reversible left anterior descending coronary artery ligation method, and the electrocardiogram ST segment was monitored continuously. Mice in all groups underwent 20 minutes of ischemia, followed by euthanasia at either 24 hours or 7 days post-reperfusion. The MIRI modeling and recovery status were determined by ST segment monitoring. The myocardial infarction area was observed by 2,3,5-triphenyltetrazolium chloride ( TTC) staining, and pathological inflammatory changes in the ischemic area of the mouse heart were observed by hematoxylin / eosin (HE) and Masson staining. Apoptosis was determined by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling, serum creatine kinase isoenzyme ( CK-MB) levels were determined by enzyme-linked immunosorbent assay, and serum levels of lactate dehydrogenase (LDH), superoxide dismutase ( SOD) activity, and malondialdehyde (MDA) were detected using appropriate kits. The effects of the three medicines on the viability of human myocardial cells (AC16) after oxygen-glucose deprivation / reperfusion (OGD/ R) were compared by cell proliferation and cytotoxicity ( Cell Counting Kit-8) assays in vitro. Results Electrocardiogram examination revealed that the average heart rate was higher during reperfusion than during ischemia, indicating MIRI. The myocardial infarction area was reduced in the ZD-3, DG-3, and ZD-5 groups compared with the model group, as shown by TTC staining (P<0. 05), and HE and Masson staining indicated that the three drugs reduced the recruitment of inflammatory cells to varying degrees and inhibited myocardial tissue fibrosis (P<0. 05). Apoptosis and serum CK-MB levels were significantly reduced in the ZD-3 group ( P<0. 001, P < 0. 01, respectively). Detection of the myocardial enzyme LDH and oxidative stress indicators SOD and MDA 24 hours and 7 days after MIRI showed that ZD-3, DG-3, and ZD-5 reduced LDH activity,while ZD-3 and DG-3 also reduced the production of oxidative stress factors (P< 0. 01). ZD-3 also increased the survival of AC16 cells after OGD/ R in vitro (P<0. 05). Conclusions The Mongolian medicines DG-3, ZD-3, and ZD-5 can protect against MIRI in mice, with ZD-3 showing the best cardioprotective effect. Their mechanism involves reducing the infiltration of inflammatory cells and inhibiting cardiac tissue fibrosis. These preliminary result suggest that, under these experimental conditions, ZD-3 is a promising drug that can effectively inhibit the effects of MIRI.

Abstract: Objective To summarize the characteristics of animal models of acute kidney injury (AKI) developed domestically and internationally, providing references for the standardization and normalization of animal model preparation for this disease. Methods We searched and collated relevant literature on AKI animal models reported in CNKI, Wanfang, VIP, SinoMed, and PubMed databases since their establishment. Data for animal strains, modeling method, modeling cycles, modeling criteria, positive drugs, detection indicators, and other parameters were analyzed. Results In total, 266 articles were included (220 in Chinese and 46 in English). The majority of animal strains were male rats, aged 8 to 10 weeks and weighing 180 g to 250 g. There were 22 modeling method; ischemia-reperfusion and intramuscular injection of glycerol were the primary single-factor modeling approaches. The modeling cycle was mostly concentrated within 14 days, with the highest number of articles recording between 6 and 24 h. The criteria for verifying model establishment were not unified; however, most articles used SCr, BUN, and renal pathological changes. Positive drugs mainly included captopril and ginsenoside. Detection indicators mainly involved comprehensive evaluations, such as renal function assessment, histopathological evaluation, and experimental animal observation. Conclusions Well-standardized AKI animal model preparation and modeling criteria with high clinical concordance are still lacking. The comprehensive application of multi-level and multi-angle detection indicators needs improvement. There remains significant research space for establishing a combined model of traditional Chinese medicine syndromes and diseases.

Abstract: Objective To investigate the impacts of microRNA-101-3p ( miR-101-3p) on the vascular endothelial growth factor A (VEGFA) / phosphatidylinositol 3-kinase (PI3K) / serine threonine protein kinase (AKT) pathway, inflammatory response, and pregnancy outcomes in rats with hypertensive disorder of pregnancy (HDP). Methods The expression levels of miR-101-3p, VEGFA, PI3K, and AKT in serum samples of 60 normal pregnant women (control group) and 60 pregnant women with HDP (HDP group) who underwent a regular prenatal check-up at our hospital from March to October 2024 were detected by RT-qPCR. An HDP rat model was constructed, and successfully modeled rats were randomly divided into HDP, NC antagomir (tail vein injection of NC antagomir), and miR-101-3p antagomir groups (tail vein injection of miR-101-3p antagomir). Ten normal pregnant rats were used as the Control group, and equal amounts of physiological saline were injected into the Control and HDP groups. Blood pressure, 24-hour urine protein, and pregnancy outcomes were evaluated in each group. RT-qPCR was used to detect the expression of miR-101-3p,VEGFA,PI3K,and AKT in placental tissues of HDP rats. ELISA was used to detect the expression of inflammatory and vascular injury factors in serum. Western blot was used to detect VEGFA, PI3K, and AKT in placental tissue. A dual-luciferase reporter gene assay verified the interaction between miR-101-3p and VEGFA. Results The expression of miR-101-3p was high, while VEGFA, PI3K, and AKT levels were low in the HDP group (P< 0. 05). The morphology and structure of placental tissue in the control group were normal. The placental tissue structure of the HDP group and NC antagomir group was blurred, with substantial inflammatory cell infiltration. The placental tissue damage and inflammatory cell infiltration of pregnant mice in the miR-101-3p antagomir group were reduced. The blood pressure, 24-hour urinary protein, miR-101-3p, IL-1β, IL-6, TNF-α, sICAM-1, and ET-1 levels in the HDP group were higher than those in the control group, while the embryo survival rate, NO, VEGFA mRNA and protein, PI3K mRNA and protein, and AKT mRNA and protein levels were lower than those in the control group (P<0. 05). The blood pressure, 24-hour urinary protein, miR-101-3p, IL-1β, IL-6, TNF- α, sICAM-1, and ET-1 levels were lower, while the embryo survival rate, NO, VEGFA mRNA and protein, PI3K mRNA and protein, and AKT mRNA and protein levels were higher in the miR-101-3p antagomir group than in the HDP and NC antagomir groups (P<0. 05). miR-101-3p can negatively regulate VEGFA. Conclusions Inhibiting miR-101-3p can activate the VEGFA/ PI3K/ AKT pathway, suppress the inflammatory response and vascular damage,and improve pregnancy outcomes.

Abstract: Objective To summarize and analyze the current status of animal models for Crohn’ s disease (CD) based on literature data mining, providing a basis for optimizing preparation method and evaluation criteria. Methods Literature related to CD animal models was retrieved from the China National Knowledge Infrastructure, Wanfang Data, and PubMed databases. Information on animal species, modeling method, detection indicators, and positive intervention strategies was extracted. A database was established using Excel software for statistical analysis. Results In total, 411 eligible Chinese and English articles were included. The majority of CD animal models used 6-to 8-week-old SD rats, C57BL / 6J mice, or BALB/ c mice, predominantly male. Modeling method could be assigned to six categories: chemical induction (primarily TNBS), genetic engineering ( e. g. , IL-10^{- / -}and TNF ^△ARE mice),spontaneous models, immune-mediated models, microbial colonization, and combination approaches. Detection indicators encompassed general phenotypic characteristics, pathological alterations, inflammatory markers, intestinal permeability, intestinal fibrosis, immunological changes, gut microbiota and metabolite profiles, and signaling pathways. Among positive interventions, Western medicine primarily uses biological agents and traditional Chinese medicine (TCM) primarily uses acupuncture and herbal compounds. These animal models are widely applied in drug efficacy evaluation, mechanistic analyses, and novel model development. Conclusions Diverse method ologies have been used to establish CD animal models, each capable of simulating various facets of CD pathology. However, model construction relies predominantly on Western medical pathogenic factors and lacks the systematic integration of TCM syndrome patterns. Furthermore, model evaluation metrics are heavily skewed towards Western pathological and molecular parameters. Importantly, TCM diagnostic parameters derived from observable animal phenotypes, such as coat condition, mental state, and fecal characteristics, have yet to be incorporated into standardized, quantitative systems. This significant gap result in a lack of “disease-syndrome combination” models that adequately reflect both Western disease pathology and TCM syndrome differentiation. Future research should focus on refining standardized modeling protocols, establishing animal models that comprehensively integrate Western disease characteristics with TCM syndrome patterns, and developing models covering the entire CD disease course. Achieving these goals will improve the reliability of research and accelerate the exploration of pathogenesis and development of novel therapeutic strategies.

Abstract: Objective To explore the method of establishing and evaluating a rat model of liver depression syndrome, and provide a reference for the standardized development of this model. Methods We conducted computer searches of the China National Knowledge Infrastructure, Wanfang, VIP, PubMed, and Web of Science databases to identify experimental studies related to rat models of liver depression syndrome from November 14, 2019,to November 14, 2024. The literature was screened according to defined inclusion and exclusion criteria. Information on publication time, animal conditions, related diseases, modeling method, modeling time, evaluation indicators, and intervention method was extracted. Data collation, frequency analysis, and association rule analysis were conducted using Excel 2021 and IBM SPSS Modeler 18. 0, and the result were displayed visually in the form of charts. Results A total of 192 eligible studies were finally included. Sprague-Dawley rats were the most commonly used rat models of liver depression syndrome ( 76. 05%), and most rats were male ( 62. 50%) and most were specific pathogen-free grade (82. 82%). The main related diseases were digestive system diseases (57. 90%). Among the syndrome types, liver depression and spleen deficiency syndrome was the most common ( 62. 68%). Multifactor modeling was used for most models ( 55. 96%), and the modeling time was concentrated within 15 ~ 21 days.Potential combinations of macroscopic syndrome evaluation indicators were also obtained, with the main intervention method including Chinese medicine compound prescriptions ( 86. 82%). Conclusions Although the rat model of liver depression syndrome is widely used, it currently has problems such as non-standard names for syndrome types, a lack of standardized modeling method, and imperfect evaluation systems. This study provides ideas and references for standardizing syndrome types, optimizing the model, and improving the evaluation system for rat models of liver depression.

Abstract: Objective To investigate the effects of Yiqi Huoxue Lishui formula ( YQHXLSF ) on mitochondrial morphology and function in heart failure (HF) model rats, via activation of the AMP-activated protein kinase ( AMPK) / peroxisome proliferator-activated receptor gamma coactivator ( PGC ) 1α signaling pathway. Methods The HF model was surgically induced in rats via ligation of the left anterior descending coronary artery, followed by a regimen of food restriction and forced exhaustive swimming. Postoperatively, rats were divided randomly into sham, model, trimetazidine (TMZ), YQHXLSF medium-dose, and YQHXLSF high-dose groups. After 4 weeks of treatment, cardiac function was assessed using echocardiography, hematoxylin-eosin and Masson staining. Reactive oxygen species (ROS) levels, mitochondrial ultrastructure, and functional changes were detected. Expression levels of AMPK/ PGC-1α pathway proteins were measured by Western blot, and mRNA expression and mitochondrial DNA (mtDNA) replication levels were evaluated by real-time polymerase chain reaction. Results YQHXLSF significantly improved cardiac function parameters (P<0. 05), attenuated myocardial fibrosis, and reduced ROS levels (P< 0.01). It also enhanced mitochondrial respiratory chain enzyme activity ( P< 0. 01) and membrane potential, and increased ATP content (P<0. 01). Western blot and RT-PCR Results showed that YQHXLSF upregulated the protein and mRNA expression levels of p-AMPK, PGC-1α, NRF-1, and TFAM, and promoted mtDNA replication ( P<0. 01). Conclusions YQHXLSF improves cardiac function and myocardial fibrosis, reduces ROS levels, augments ATP synthesis in rodent models of heart failure through preserving mitochondrial structural integrity and functional homeostasis, stimulating mitochondrial biogenesis, and fine-tuning energetic metabolism within mitochondria. The activation of the AMPK/ PGC-1α signaling axis appears to serve as a fundamental mechanism underlying these observed effects.

Abstract:We aimed to establish a scientific regulatory system to improve the supervision of laboratory animal welfare and ethics. The system included 12 regulatory indexes, and targeted evaluation criteria were formulated based on the characteristics of the indexes. The regulatory indexes were supervised by inspecting the sites and using specialized techniques such as small-animal micro-computed tomography and magnetic resonance imaging. The system established a dynamic regulatory mechanism combining project approval review, process supervision, and final review. The system also implemented a regulatory process including both online and offline method. This system will help to prevent the occurrence of incidents that violate technological ethics, standardize regulatory procedures, and provide a reference for the supervision of welfare and ethics in the production and use of laboratory animals.

Abstract:Premature ovarian insufficiency ( POI) is a clinical syndrome of premature ovarian failure in women of childbearing age, characterized by menstrual disorder, fertility decline, and perimenopausal symptoms before 40 years of age. Recent studies showed that extracellular vesicles (EVs), as a natural carrier of bioactive molecules, could effectively transport nucleic acids, proteins, and other functional substances, and showed significant therapeutic potential for improving ovarian tissue damage, promoting granular cell proliferation, and inhibiting apoptosis. Although EVs have broad clinical application prospects in the field of regenerative medicine, they still face technical bottlenecks in terms of their targeted delivery efficiency, biological stability, and large-scale preparation.Innovative modification strategies based on bioengineering technologies, including membrane surface functionalization,precise content loading, and microenvironment pretreatment, provide effective solutions to overcome existing technical barriers. This review considers the biological characteristics of EVs and their mechanism of action in the treatment of POI, with an emphasis on the key technological breakthroughs of engineering modification strategies for improving the therapeutic efficacy of EVs, and the prospects for their future translational application in the field of reproductive medicine.

Abstract:Methamphetamine use disorder (MUD) is a refractory disorder with limited treatment options.There are evidences that neuropeptides might be a new target for the treatment of MUD. Studying the regulatory mechanism of neuropeptides in MUD may provide new options for treatment. However, there are many kinds of neuropeptides, the mechanism of action is complex, and clinical drug references are limited. This review focuses on orexin (OX), oxytocin (OT), vasopressin (VP), neurotensin (NT), neuropeptide S (NPS), neuropeptide Y (NPY), somatostatin (SST), pituitary adenylate cyclase-activating peptide (PACAP), vasoactive intestinal peptide (VIP), glucagon-like peptide-1 (GLP-1), and other neuropeptides as well. The regulatory role and mechanism of peptides in MUD are summarized, providing new directions for research and supporting the application of neuropeptides in the treatment of MUD.

Abstract:Major depressive disorder is a mental disorder characterized by persistent low mood, loss of interest, loss of appetite, and sleep disorders. At present, monoamines are the main drugs for the treatment of this disease; however, the clinical application of these drugs is limited. The multi-target, multi-link, and holistic regulation of traditional Chinese medicine (TCM) makes it a promising treatment option. In recent years, the role of the GR/ NF-κB/ NLRP3 signaling pathway in the pathogenesis and treatment of depression has attracted attention.Studies have shown that this signaling pathway is closely related to the hypothalamic-pituitary-adrenal axis, the inhibition of neuroinflammation, and the regulation of nerve cell pyroptosis. This article reviews the mechanism underlying the antidepressant effect of TCM via the regulation of the GR/ NF-κB/ NLRP3 signaling pathway, providing a theoretical basis for treatment and further research on depression.

Abstract:Sj?gren’ s syndrome ( SS) is a chronic autoimmune disease with a complex pathogenesis. In addition to lymphocyte infiltration and inflammatory damage of the glands, it often involves multiple systems.However, treatment options are limited. Studies have found that mitochondrial quality control dysfunction is closely related to inflammation in autoimmune diseases. This article evaluates the correlation between mitochondrial quality control dysfunction and glandular damage in SS, aimed at broadening the horizons for the treatment of SS.

Abstract:Neuroblastoma (NB) is the most common extracranial solid tumor in children, characterized by high mortality and poor prognosis. With advances in molecular biology and genomics research, it has become increasingly clear that the development and progression of NB are driven by the dysregulation of complex molecular networks. To develop safer and more efficient precision diagnostic and therapeutic strategies, it is particularly important to gain a deeper understanding of the molecular mechanisms underlying the pathogenesis of NB. This article systematically reviews research progress on key regulatory factors from three dimensions: tumor development (including abnormal proliferation, migration, invasion, and EMT), inflammatory responses, and apoptosis. We examined the effects of various genes, including MYCN, ALK, BDNF, and PHOX2B, on malignant behaviors of NB cells, analyzed the tumor-promoting effects of inflammatory signals, including NF-κB, COX-2/ PGE2, MyD88, and HMGB1, and illustrated the mechanisms of apoptosis-related factors, including the Bcl-2 family, p53-MDM2 axis,and TRAIL. These findings deepen our understanding of the molecular pathological mechanisms of NB, and more importantly, reveal multiple therapeutic targets with translational potential, providing systematic theoretical references for basic research and clinical treatment. More broadly, this review is expected to promote further research from molecular mechanisms to clinical translation, ultimately aiming to improve the prognosis of pediatric patients.