ObjectiveTraditional Chinese medicine (TCM) constitutes a valuable cultural heritage and an important source of antitumor compounds. Poria (Poria cocos (Schw.) Wolf), the dried sclerotium of a polyporaceae fungus, was first documented in Shennong’s Classic of Materia Medica and has been used therapeutically and dietarily in China for millennia. Traditionally recognized for its diuretic, spleen-tonifying, and sedative properties, modern pharmacological studies confirm that Poria exhibits antioxidant, anti-inflammatory, antibacterial, and antitumor activities. Pachymic acid (PA; a triterpenoid with the chemical structure 3β-acetyloxy-16α-hydroxy-lanosta-8,24(31)-dien-21-oic acid), isolated from Poria, is a principal bioactive constituent. Emerging evidence indicates PA exerts antitumor effects through multiple mechanisms, though these remain incompletely characterized. Neuroblastoma (NB), a highly malignant pediatric extracranial solid tumor accounting for 15% of childhood cancer deaths, urgently requires safer therapeutics due to the limitations of current treatments. Although PA shows multi-mechanistic antitumor potential, its efficacy against NB remains uncharacterized. This study systematically investigated the potential molecular targets and mechanisms underlying the anti-NB effects of PA by integrating network pharmacology-based target prediction with experimental validation of multi-target interactions through molecular docking, dynamic simulations, and in vitro assays, aimed to establish a novel perspective on PA’s antitumor activity and explore its potential clinical implications for NB treatment by integrating computational predictions with biological assays. MethodsThis study employed network pharmacology to identify potential targets of PA in NB, followed by validation using molecular docking, molecular dynamics (MD) simulations, MM/PBSA free energy analysis, RT-qPCR and Western blot experiments. Network pharmacology analysis included target screening via TCMSP, GeneCards, DisGeNET, SwissTargetPrediction, SuperPred, and PharmMapper. Subsequently, potential targets were predicted by intersecting the results from these databases via Venn analysis. Following target prediction, topological analysis was performed to identify key targets using Cytoscape software. Molecular docking was conducted using AutoDock Vina, with the binding pocket defined based on crystal structures. MD simulations were performed for 100 ns using GROMACS, and RMSD, RMSF, SASA, and hydrogen bonding dynamics were analyzed. MM/PBSA calculations were carried out to estimate the binding free energy of each protein-ligand complex. In vitro validation included RT-qPCR and Western blot, with GAPDH used as an internal control. ResultsThe CCK-8 assay demonstrated a concentration-dependent inhibitory effect of PA on NB cell viability. GO analysis suggested that the anti-NB activity of PA might involve cellular response to chemical stress, vesicle lumen, and protein tyrosine kinase activity. KEGG pathway enrichment analysis suggested that the anti-NB activity of PA might involve the PI3K/AKT, MAPK, and Ras signaling pathways. Molecular docking and MD simulations revealed stable binding interactions between PA and the core target proteins AKT1, EGFR, SRC, and HSP90AA1. RT-qPCR and Western blot analyses further confirmed that PA treatment significantly decreased the mRNA and protein expression of AKT1, EGFR, and SRC while increasing the HSP90AA1 mRNA and protein levels. ConclusionIt was suggested that PA may exert its anti-NB effects by inhibiting AKT1, EGFR, and SRC expression, potentially modulating the PI3K/AKT signaling pathway. These findings provide crucial evidence supporting PA’s development as a therapeutic candidate for NB.

OBJECTIVE: To investigate the effect of zedoarondiol on neovascularization of atherosclerotic (AS) plaque by exosomes experiment. METHODS: ApoE^-/- mice were fed with high-fat diet to establish AS model and treated with high- and low-dose (10, 5 mg/kg daily) of zedoarondiol, respectively. After 14 weeks, the expressions of anti-angiogenic protein thrombospondin 1 (THBS-1) and its receptor CD36 in plaques, as well as platelet activation rate and exosome-derived miR-let-7a were detected. Then, zedoarondiol was used to intervene in platelets in vitro, and miR-let-7a was detected in platelet-derived exosomes (Pexo). Finally, human umbilical vein endothelial cells (HUVECs) were transfected with miR-let-7a mimics and treated with Pexo to observe the effect of miR-let-7a in Pexo on tube formation. RESULTS: Animal experiments showed that after treating with zedoarondiol, the neovascularization density in plaques of AS mice was significantly reduced, THBS-1 and CD36 increased, the platelet activation rate was markedly reduced, and the miR-let-7a level in Pexo was reduced (P<0.01). In vitro experiments, the platelet activation rate and miR-let-7a levels in Pexo were significantly reduced after zedoarondiol's intervention. Cell experiments showed that after Pexo's intervention, the tube length increased, and the transfection of miR-let-7a minics further increased the tube length of cells, while reducing the expressions of THBS-1 and CD36. CONCLUSION Zedoarondiol has the effect of inhibiting neovascularization within plaque in AS mice, and its mechanism may be potentially related to inhibiting platelet activation and reducing the Pexo-derived miRNA-let-7a level.
Animals ; MicroRNAs/genetics* ; Exosomes/drug effects* ; Plaque, Atherosclerotic/genetics* ; Neovascularization, Pathologic/genetics* ; Human Umbilical Vein Endothelial Cells/metabolism* ; Humans ; Blood Platelets/drug effects* ; Apolipoproteins E/deficiency* ; Thrombospondin 1/metabolism* ; CD36 Antigens/metabolism* ; Platelet Activation/drug effects* ; Male ; Mice ; Mice, Inbred C57BL

Neuropathic pain, a debilitating condition caused by dysfunction of the somatosensory nervous system, remains difficult to treat due to limited understanding of its molecular mechanisms. Bioinformatics analysis identified cerebellin 2 (CBLN2) as highly enriched in human and murine proprioceptive and nociceptive neurons. We found that CBLN2 expression is persistently upregulated in dorsal root ganglia (DRG) following spinal nerve ligation (SNL) in mice. In addition, transcription factor SOX11 binds to 12 cis-regulatory elements within the Cbln2 promoter to enhance its transcription. SNL also induced SOX11 upregulation, with SOX11 and CBLN2 co-localized in nociceptive neurons. The siRNA-mediated knockdown of Sox11 or Cbln2 attenuated SNL-induced mechanical allodynia and thermal hyperalgesia. High-throughput sequencing of DRG following intrathecal injection of CBLN2 revealed widespread gene expression changes, including upregulation of numerous NF-κB downstream targets. Consistently, CBLN2 activated NF-κB signaling, and inhibition with pyrrolidine dithiocarbamate reduced CBLN2-induced pain hypersensitivity, proinflammatory cytokines and chemokines production, and neuronal hyperexcitability. Together, these findings identified the SOX11/CBLN2/NF-κB axis as a critical mediator of neuropathic pain and a promising target for therapeutic intervention.
Animals ; Neuralgia/metabolism* ; Ganglia, Spinal/metabolism* ; Up-Regulation ; Mice ; NF-kappa B/metabolism* ; SOXC Transcription Factors/genetics* ; Male ; Neuroinflammatory Diseases/metabolism* ; Mice, Inbred C57BL ; Nerve Tissue Proteins/genetics* ; Hyperalgesia/metabolism* ; Signal Transduction ; Spinal Nerves

Objective:To explore the role of combined detection of cell free BMPR1A and PLAC8 gene methylation in plasma in predicting postoperative recurrence of hepatocellular carcinoma.Methods:Case series study. Patients with stage Ⅰ-Ⅳ hepatocellular carcinoma who were treated at the Third Affiliated Hospital of Sun-Yat-sen University from January 2022 to July 2023 were selected. All enrolled patients underwent alpha fetoprotein (AFP) and imaging assessments 1 month, 3 months, 6 months, 9 months, and 12 months after treatment. Simultaneously, peripheral blood of patients was extracted for plasma circulating tumor DNA (ctDNA) methylation detection, and the results of free BMPR1A and PLAC8 gene methylation detection in patients′ plasma after treatment were compared with the positive rate of traditional tumor marker AFP detection. Draw the receiver operating characteristic curve (ROC) of the subjects to demonstrate the effectiveness of this method in predicting the recurrence of hepatocellular carcinoma. Based on the results of cell free DNA methylation and whether AFP is more than 7 μg/L, hepatocellular carcinoma patients were divided into high-risk methylation group (12 cases), low-risk methylation group (21 cases), high-risk AFP group (15 cases), and Kaplan Meier survival analysis was performed on them.Results:The sensitivity and specificity of combined detection of free BMPR1A PLAC8 gene methylation in plasma for predicting liver cancer recurrence were 66.7% and 88.9%, respectively. The area under curve (AUC) of BMPR1A PLAC8 gene methylation detection for liver cancer recurrence were 0.770 and 0.778, and the AFP was 0.522 in ROC curve analysis. Compared to imaging examinations, cell free DNA methylation detection can detect the recurrence of hepatocellular carcinoma on average by 58.3 days in advance(53.8 days vs 112.1 days). The progression free survival rate of the high-risk group based on free DNA methylation prediction at 400 days was 22.2%, significantly lower than the low-risk group (76.2%, P<0.001). Conclusion:Compared to AFP, detecting the methylation of BMPR1A and PLAC8 genes can predict the recurrence of hepatocellular carcinoma more accurately, making it a practical method for monitoring liver cancer recurrence.

BackgroundCombination of antipsychotic drugs and modified electroconvulsive therapy （MECT） is currently a commonly used method for treating schizophrenia， but its efficacy varies among different patient groups. ObjectiveTo explore the therapeutic effects of MECT on schizophrenia patients living in different urban versus rural environments， so as to provide references for the selection of treatment plans based on patients' residence. MethodsA total of 587 patients hospitalized at Luzhou Mental Health Center， Zigong Mental Health Center and Yibin Fourth People's Hospital from May 2018 to August 2022， who met the diagnostic criteria for schizophrenia in the Diagnostic and Statistical Manual of Mental Disorders， fifth edition （DSM-5） ，were included in the study. Patients were divided into two groups： medication-only group （n=106） and MECT combined with medication group （n=481）. In MECT combined with medication group， 24 rural patients residing in urban areas were excluded， leaving the remaining patients divided into urban group （n=103） and rural group （n=354） based on their place of residence. Positive and Negative Syndrome Scale （PANSS） was used to assess the severity of symptoms. Clinical efficacy was evaluated using PANSS score reduction rate， and covariance analysis was used to compare the therapeutic effects of different patients. ResultsThe differences of reduction rate of PANSS total score， positive symptom scale score and negative symptom scale score as well as treatment effectiveness rate between MECT combined with medication group and medication-only group were statistically significant （F=11.149， 12.111， 31.725， χ²=14.010， P<0.01）. Statistically significant differences were also observed in reduction rate of PANSS total score and positive symptom subscale score as well as treatment effectiveness rate between urban and rural patients in MECT combined with medication group （F=3.946， 4.523， χ²=4.033， P<0.05）. ConclusionThe efficacy of MECT combined with medication may be superior to medication alone in the treatment of schizophrenia， and the combined therapy may be more effective in urban patients than that in rural patients， with potentially more pronounced improvements in positive symptoms.

Objective:To evaluate the efficacy and safety of antaitasvir phosphate 100 mg or 200 mg combined with yiqibuvir for 12 weeks in patients with various genotypes of chronic hepatitis C, without cirrhosis or compensated stage cirrhosis.Methods:Patients with chronic hepatitis C (without cirrhosis or compensated stage cirrhosis) were randomly assigned to the antaitasvir phosphate 100 mg+yiqibuvir 600 mg group (100 mg group) or the antaitasvir phosphate 200 mg+yiqibuvir 600 mg group (200 mg group) in a 1∶1 ratio. The drugs were continuously administered once a day for 12 weeks and observed for 24 weeks after drug withdrawal. The drug safety profile was assessed concurrently with the observation of the sustained virological response (SVR12) in the two patient groups 12 weeks following the drug cessation. The intention-to-treat concept was used to define as closely as possible a full analysis set, including all randomized cases who received the experimental drug at least once. The safety set was collected from all subjects who received the experimental drug at least once (regardless of whether they participated in the randomization group) in this study. All efficacy endpoints and safety profile data were summarized using descriptive statistics. The primary efficacy endpoint was SVR12. The primary analysis was performed on a full analysis set. The frequency and proportion of cases were calculated in the experimental drug group (antaitasvir phosphate capsules combined with yiqibuvir tablets) that achieved "HCV RNA

Objective To investigate the incidence rate,clinical characteristics,and prognosis of neonatal stroke in Shenzhen,China.Methods Led by Shenzhen Children's Hospital,the Shenzhen Neonatal Data Collaboration Network organized 21 institutions to collect 36 cases of neonatal stroke from January 2020 to December 2022.The incidence,clinical characteristics,treatment,and prognosis of neonatal stroke in Shenzhen were analyzed.Results The incidence rate of neonatal stroke in 21 hospitals from 2020 to 2022 was 1/15 137,1/6 060,and 1/7 704,respectively.Ischemic stroke accounted for 75％(27/36);boys accounted for 64％(23/36).Among the 36 neonates,31(86％)had disease onset within 3 days after birth,and 19(53％)had convulsion as the initial presentation.Cerebral MRI showed that 22 neonates(61％)had left cerebral infarction and 13(36％)had basal ganglia infarction.Magnetic resonance angiography was performed for 12 neonates,among whom 9(75％)had involvement of the middle cerebral artery.Electroencephalography was performed for 29 neonates,with sharp waves in 21 neonates(72％)and seizures in 10 neonates(34％).Symptomatic/supportive treatment varied across different hospitals.Neonatal Behavioral Neurological Assessment was performed for 12 neonates(33％,12/36),with a mean score of(32±4)points.The prognosis of 27 neonates was followed up to around 12 months of age,with 44％(12/27)of the neonates having a good prognosis.Conclusions Ischemic stroke is the main type of neonatal stroke,often with convulsions as the initial presentation,involvement of the middle cerebral artery,sharp waves on electroencephalography,and a relatively low neurodevelopment score.Symptomatic/supportive treatment is the main treatment method,and some neonates tend to have a poor prognosis.

Aim To explore the differences in sedative and hypnotic effects of Semen Ziziphi Spinosae(SZS)before and after processing based on network pharma-cology and animal experiments.Methods The chemi-cal components and corresponding targets of SZS were collected through relevant platforms and databases,the insomnia and sleep disorder targets were retrieved,and the intersection targets of drugs and diseases were ob-tained.The protein interaction relationships were con-structed,and the Chinese medicinal herb-component-target-pathway network was drawn.Then database was used to analyze pathway enrichment.Based on the pre-dicted results,the effects of different SZS products on Kunming mice were evaluated through pentobarbital in-duced sleep test,behavioral analysis,brain tissue relat-ed gene mRNA levels,and plasma neurotransmitters.Results The target genes related to SZS and insomnia were acetylcholinesterase(ACHE),alpha-1B adrener-gic receptor(ADRA1B),solute carrier family 6(neu-rotransmitter transporter,serotonin),member 4(SLC6 A4),which might play a role through 9 related pathways and 69 biological processes such as calcium signaling pathway,salivary secretion,and so on.In vi-vo experiments found that SZS could reduce mouse ac-tivity,enhance the hypnotic effect of pentobarbital sodi-um,lower the levels of ACEE,ADRA1B,and SLC6A4 mRNA in cortex and hippocampus,and regulate the levels of acetylcholine,adrenaline,and other substances in plasma,all of which could be used in combination with raw and fried methods.The effect was proportion-al to the dosage of the drug.Conclusions SZS has sedative and hypnotic effects,and high doses of crude and parched SZS combined decoction have better effects.This effect may be caused by affecting the lev-els of neurotransmitters and their related receptors,me-diating the central nervous system.

Immunotherapy has become a mainstream treatment for cancer.However,the immunosuppressive tumor microenvironment hinders the antigen extraction and presentation by immune cells,resulting in insufficient infiltration and activation of cytotoxic T cells.Moreover,patient variability and the systemic distribution of immunotherapeutic agents can cause toxic side effects,such as excessive activ-ation or immunosuppression.The extratumoral toxicity and challenges in penetrating the tumor microenvironment hinder the effectiveness of immunotherapy on solid tumors.Recently,researchers have developed immunotherapy platforms using polymers,nucleic acids,and cells capable of logical processing based on signal inputs.These platforms can target tumors and perform logical processing based on various in-puts from the tumor microenvironment or external signals.This review briefly introduces logic-gated platforms designed using synthetic nanocarriers,nucleic acids,and chimeric antigen receptor T-cells(CAR-T)and discusses research progress in immunotherapy,aiming to provide foresight by comparing the advantages and disadvantages of each platform.

As artificial intelligence technology rapidly advances, its deployment within the medical sector presents substantial ethical challenges. Consequently, it becomes crucial to create a standardized, transparent, and secure framework for processing medical data. This includes setting the ethical boundaries for medical artificial intelligence and safeguarding both patient rights and data integrity. This consensus governs every facet of medical data handling through artificial intelligence, encompassing data gathering, processing, storage, transmission, utilization, and sharing. Its purpose is to ensure the management of medical data adheres to ethical standards and legal requirements, while safeguarding patient privacy and data security. Concurrently, the principles of compliance with the law, patient privacy respect, patient interest protection, and safety and reliability are underscored. Key issues such as informed consent, data usage, intellectual property protection, conflict of interest, and benefit sharing are examined in depth. The enactment of this expert consensus is intended to foster the profound integration and sustainable advancement of artificial intelligence within the medical domain, while simultaneously ensuring that artificial intelligence adheres strictly to the relevant ethical norms and legal frameworks during the processing of medical data.
Artificial Intelligence/legislation & jurisprudence* ; Humans ; Consensus ; Computer Security/standards* ; Confidentiality/ethics* ; Informed Consent/ethics*