ObjectiveHepatocellular carcinoma (HCC) represents 90% of all primary liver cancers. The main risk factors associated with HCC include viral hepatitis (B and/or C), alcohol abuse, and metabolic dysfunction-associated steatotic liver disease (MASLD), which progressively advance to liver fibrosis, cirrhosis, and ultimately evolve into HCC. Surgical resection represents the most effective treatment for HCC, while recent advances in immunotherapy, including immune checkpoint inhibitors and adoptive cell therapies, have provided improved treatment prospects for patients with unresectable HCC. However, the complex metabolic heterogeneity of HCC limits the therapeutic efficacy. Metabolic intermediates acyl-CoA not only provide energy and substrates for numerous biochemical reactions but also serve as donors for protein lysine acylation, a major class of post-translational modification (PTM). Therefore, a deeper understanding of the molecular mechanisms underlying protein lysine acylation and hepatocarcinogenesis is urgently needed. MethodsThe levels of protein lysine acylation and silence information regulator 5 (SIRT5) expression levels in clinical HCC samples were analyzed by Western blot. Quantitative malonylome and succinylome of HCC samples were analyzed by antibody-based affinity enrichment coupled with tandem mass spectrometry. The proliferation of HCC cells was analyzed with Cell Counting Kit-8 (CCK-8) assays, the apoptosis was quantified by Annexin V-FITC/propidium iodide (PI) staining coupled with flow cytometry, and the ability of cells to migrate was assayed by Transwell assays. The enzymatic activity of glutathione S-transferase Mu 1 (GSTM1) was quantified. Transgenic mice with hepatic overexpression of SIRT5 were constructed using CRISPR-Cas9, and primary hepatocarcinogenesis was induced by administration of diethylnitrosamine. ResultsWestern blot analysis indicated that the expression level of SIRT5 was elevated in clinical samples from HCC patients, and the levels of lysine malonylation, glutarylation, and succinylation were significantly reduced in HCC tissues. Knockout of SIRT5 in MHCC-97H and MHCC-97L hepatoma cells suppressed cell proliferation, and increased the percentage of apoptotic cells significantly. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses of the differentially malonylome and succinylome of HCC samples revealed significant enrichment in two major classes of biological processes: core energy metabolism (e.g., glycolysis/gluconeogenesis, tricarboxylic acid metabolic process, fatty acid beta oxidation) and detoxification and oxidative stress response (e.g., response to toxic substance, chemical carcinogenesis, reactive oxygen species (ROS)). SIRT5 removes malonylation from lysine residues in GSTM1 and restores its detoxification activity, which is crucial for the survival of hepatocytes under stressed conditions. More importantly, in vivo experiment indicated that hepatic-specific overexpression of SIRT5 in mice accelerated diethylnitrosamine-induced liver fibrosis and hepatocarcinogenesis, indicating the critical role of SIRT5 in HCC progression. ConclusionThis study highlights the previously unrecognized SIRT5-GSTM1 axis as a key regulator in hepatocarcinogenesis, and suggests a potential target for the treatment of patients with HCC.

Endoscopic transforaminal lumbar interbody fusion (TLIF) offers substantial advantages in the management of degenerative spinal diseases, including accelerated postoperative recovery. However, its technical complexity and steep learning curve pose risks for nerve root injury. Optimizing nerve root protection in full-endoscopic facet-sparing TLIF (FE fs-TLIF) and full-endoscopic facet-resecting TLIF (FE fr-TLIF) is essential for enhancing surgical safety. This study aimed to improve the nerve root protection in FE fs-TLIF and FE fr-TLIF by optimizing cage glider selection and insertion techniques based on the specific cage shape—banana-shaped or bullet-shaped. The goal was to ensure safe cage positioning and mitigate nerve root injury during discectomy, endplate preparation, and cage insertion. These strategies were validated through cadaveric simulations and clinical implementation. In FE fr-TLIF utilizing bullet-shaped (straight) cages, one-tip and two-tip cage gliders effectively protected the traversing nerve root by facilitating medial cage entry, thereby minimizing irritation of the exiting nerve root. Conversely, in FE fr-TLIF with banana-shaped cages, the lateral tilt of the cage holder during implantation required the use of a two-tip cage glider to protect the traversing and exiting nerve roots, thereby mitigating the potential risk of nerve irritation. In FE fs-TLIF, a one-tip cage glider is preferred for safeguarding the exiting nerve root, while the traversing root is inherently protected by the medial wall of the facet joint. The use of a two-tip cage glider in FE fs-TLIF can cause injury to the nerve root during glider insertion. In addition to the selection of cage gliders, improper cage insertion steps can also contribute to postoperative neurapraxia. The appropriate selection of cage gliders with corresponding insertion techniques is critical for nerve root protection in endoscopic TLIF. Tailoring these choices to the specific approach (FE fs-TLIF or FE fr-TLIF) and cage type (banana or bullet) enhances surgical safety and clinical outcomes.

ObjectiveTo investigate the mechanism of action of Kaixinsan in the treatment of Alzheimer's disease （AD） based on network pharmacology， molecular docking， and animal experimental validation. MethodsThe Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform（TCMSP） and the Encyclopedia of Traditional Chinese Medicine（ETCM） databases were used to obtain the active ingredients and targets of Kaixinsan. GeneCards， Online Mendelian Inheritance in Man（OMIM）， TTD， PharmGKB， and DrugBank databases were used to obtain the relevant targets of AD. The intersection （common targets） of the active ingredient targets of Kaixinsan and the relevant targets of AD was taken， and the network interaction analysis of the common targets was carried out in the STRING database to construct a protein-protein interaction（PPI） network. The CytoNCA plugin within Cytoscape was used to screen out the core targets， and the Metascape platform was used to perform gene ontology（GO） functional enrichment analysis and Kyoto encyclopedia of genes and genomes（KEGG） pathway enrichment analysis. The “drug-active ingredient-target” interaction network was constructed with the help of Cytoscape 3.8.2， and AutoDock Vina was used for molecular docking. Scopolamine （SCOP） was utilized for modeling and injected intraperitoneally once daily. Thirty-two male C57/BL6 mice were randomly divided into blank control （CON） group （0.9% NaCl， n=8）， model （SCOP） group （3 mg·kg^-1·d^-1， n=8）， positive control group （3 mg·kg^-1·d^-1 of SCOP+3 mg·kg^-1·d^-1 of Donepezil， n=8）， and Kaixinsan group （3 mg·kg^-1·d^-1 of SCOP+6.5 g·kg^-1·d^-1 of Kaixinsan， n=8）. Mice in each group were administered with 0.9% NaCl， Kaixinsan， or Donepezil by gavage twice a day for 14 days. Morris water maze experiment was used to observe the learning memory ability of mice. Hematoxylin-eosin （HE） staining method was used to observe the pathological changes in the CA1 area of the mouse hippocampus. Enzyme linked immunosorbent assay（ELISA） was used to determine the serum acetylcholine （ACh） and acetylcholinesterase （AChE） contents of mice. Western blot method was used to detect the protein expression levels of signal transducer and activator of transcription 3（STAT3） and nuclear transcription factor（NF）-κB p65 in the hippocampus of mice. ResultsA total of 73 active ingredients of Kaixinsan were obtained， and 578 potential targets （common targets） of Kaixinsan for the treatment of AD were screened out. Key active ingredients included kaempferol， gijugliflozin， etc.. Potential core targets were STAT3， NF-κB p65， et al. GO functional enrichment analysis obtained 3 124 biological functions， 254 cellular building blocks， and 461 molecular functions. KEGG pathway enrichment obtained 248 pathways， mainly involving cancer-related pathways， TRP pathway， cyclic adenosine monophosphate（cAMP） pathway， and NF-κB pathway. Molecular docking showed that the binding of the key active ingredients to the target targets was more stable. Morris water maze experiment indicated that Kaixinsan could improve the learning memory ability of SCOP-induced mice. HE staining and ELISA results showed that Kaixinsan had an ameliorating effect on central nerve injury in mice. Western blot test indicated that Kaixinsan had a down-regulating effect on the levels of NF-κB p65 phosphorylation and STAT3 phosphorylation in the hippocampal tissue of mice in the SCOP model. ConclusionKaixinsan can improve the cognitive impairment function in SCOP model mice and may reduce hippocampal neuronal damage and thus play a therapeutic role in the treatment of AD by regulating NF-κB p65， STAT3， and other targets involved in the NF-κB signaling pathway.

For middle-aged and elderly patients with conditions such as spinal fractures and degenerative spinal diseases, spinal internal fixation is a core surgical procedure for reconstructing spinal stability, heavily relying on the biomechanical stability provided by pedicle screw systems. Whereas, these patients are often complicated by osteoporosis that can significantly compromise the stability of the bone-pedicle screw interface, leading to a marked increase in pedicle screw loosening and surgical failure rates. The bone cement-augmented pedicle screw technique, which involves injecting bone cement into the vertebral body or screw trajectory to optimize the mechanical properties of the bone-pedicle screw composite, has been proven to significantly enhance fixation strength and effectively prevent screw-related failures, thereby reducing the incidence of internal fixation failure in high-risk populations undergoing spinal fusion. However, the widespread clinical application of this technique has faced challenges such as inaccurate clinical decision-making (indication and contraindication selection), non-standardized operative practices, and insufficient awareness of complication prevention, resulting in considerable variability in clinical outcomes and even severe complications. To address this, Prof. Luo Fei from First Affiliated Hospital of Army Medical University initiated the project and the Chinese Association Orthopaedic Surgeons organized relevant experts to develop the Evidence-based clinical practice guideline for bone cement-augmented pedicle screw technique ( version 2025), based on current evidence. The guidelines put forward 8 recommendations regarding the clinical value, scope of application, and operational standards of the technique, aiming to provide evidence-based medical support and technical standardization for clinical decision-making.

This study aims to compare the vaccination rates and incidence of adverse reaction rates following administration of two domestically produced human papillomavirus (HPV) vaccines in individuals aged 9-30 years,investigate the impact of distinct manufacturing processes and vaccination schedules on adverse reaction rates. From November 2023 to June 2024, the Immunization Planning Department of Liuzhou Center for Disease Control and Prevention conducted a single-center, randomized, open-label, parallel-group trial using community-based recruitment of eligible participants aged 9 to 30 years. Participants were randomly assigned to receive either of two domestically produced HPV vaccines (Walrinvax or Cecolin). As specified in the vaccine package inserts, subjects were stratified into a two-dose regimen group (aged 9-14 years) and a three-dose regimen group (aged 15-30 years). Vaccination rates were recorded, and adverse reactions within 0-30 days post-vaccination were monitored. The results showed that a total of 400 participants were enrolled. Both the full vaccination rate and the timely completion rate were significantly higher in the two-dose regimen group compared to the three-dose regimen group (Fisher′s exact test, P<0.01; χ2=7.06, P<0.01). A total of 985 doses were administered. The overall adverse reaction rate was 18.78% (185/985), with local and systemic reactions occurring at 8.02% (79/985) and 10.76% (106/985), respectively. The most frequent adverse reactions were injection site pain (4.97%, 49/985) and fever (4.47%, 44/985). No grade 4 or special-interest adverse events were reported.The incidence of adverse reactions for the two domestic HPV vaccines with different production processes (at 0/6 months) was 13.96% (55/394) and 17.46% (69/395) respectively, with no statistically significant difference (χ2=1.83, P>0.05).The adverse reaction rate was significantly lower in the 9-14 years group (9.77%) compared the 15-30 years group (24.91%)(χ 2=35.67, P<0.01). In conclusion, both domestic HPV vaccines demonstrated a favorable safety profile in the 9-30 years age group, with mostly mild adverse reactions. Compared to the three-dose schedule (15-30 years group), the two-dose HPV vaccination schedule (9-14 years group) significantly reduced the incidence of adverse reactions and improved vaccination compliance.

Objective To investigate the efficacy of Xuanbi Decoction as an adjuvant therapy for rheumatoid arthritis(RA)with dampness-heat obstruction syndrome,and its impacts on the interleu-kin-23(IL-23)/helper T cell 17(Th 17)inflammatory axis,as well as the levels of matrix metallo-proteinase-3(MMP-3)and tissue inhibitor of metalloproteinase-1(TIMP-1).Methods A total of 95 RA patients with dampness-heat obstruction syndrome were selected as the study subjects,and randomly divided into control group(48 cases)and observation group(47 cases).The control group received western medicine treatment,while the observation group received Xuanbi Decoction treat-ment based on the control group.The clinical efficacy,traditional Chinese medicine(TCM)syn-drome scores,imaging assessment results,disease activity,indicators of the IL-23/Th17 inflammatory axis,MMP-3,TIMP-1 and adverse reactions were compared between the two groups.Results The total effective rate in the observation group was 95.74％,which was significantly higher than 81.25％in the control group(P＜0.05).After treatment,the TCM syndrome scores(joint pain,joint swell-ing,yellow and greasy tongue coating as well as slippery and rapid pulse)in the observation group were significantly lower than those in the control group(P＜0.05).After treatment,the DAS28 and Sharp scores in the observation group were significantly lower than those in the control group(P＜0.05).After treatment,the levels of IL-23,Th17,IL-17 and MMP-3 in the observation group were significantly lower than those in the control group,while the TIMP-1 level was significantly higher(P＜0.05).There was no statistically significant difference in the incidence of adverse reactions between the two groups(P＞0.05).Conclusion Xuanbi Decoction as an adjuvant therapy for RA patients with dampness-heat obstruction syndrome demonstrates significant efficacy and high safety.

This study was aimed at investigating the effects of demethylase fat mass and obesity-associated protein(FTO)and methyltransferase methyltransferase like protein 3(METTL3),key molecules in N6-methyladenosine(m6A)modification,on the replication and proliferation of Japanese encephalitis virus(JEV).Recombinant lentiviruses were generated by packaging the FTO and green fluorescent protein into lentiviral vectors.Neuro2a cells,a mouse neuroblastoma cell line,were infected with the lentivirus,and stable FTO-expressing cell lines were obtained through puromycin selection.Successful overexpression of FTO was confirmed through fluorescence microscopy,real-time quantitative PCR,and western blot analysis.When Neuro2a cells overexpressing FTO were infected with JEV,the overexpression of FTO decreased JEV replication in the cells,and increased the expression of interferon(IFN)and related molecules.Additionally,treatment of JEV-infected Neuro2a cells with the METTL3-specific inhibitor STM2457 resulted in a dose-dependent decrease in JEV replication and viral protein expression.These findings suggested that lowering m6A methylation levels inhibits JEV replication,thus shedding light on the regulatory role of methylation modification in JEV replication.

In recent years,the global prevalence of myopia has remained high,seriously endangering the eye health of adolescents.A large number of studies have confirmed that orthokeratology lens can control or delay the progression of my-opia and reduce the incidence of fundus lesions in high myopia.Although the efficacy of myopia control with orthokeratolo-gy has been widely recognized,its exact mechanism of action is still unclear,and there are many hypotheses.This paper re-views the role of factors such as accommodation,defocus,choroidal thickness,high-order aberrations and biomechanics in myopia control with orthokeratology,and explores how these factors jointly affect the development of myopia.

Objective:To construct a prognostic model related to cellular senescence in gastric adenocarcinoma by bioinforma-tics tools and analyze the immune microenvironment.Methods:Gene expression data and corresponding clinical information of gastric adenocarcinoma patients were downloaded from TCGA database.Cellular senescence-related genes(CSRGs)were downloaded from CellAge database.The limma package was used to screen for differentially expressed CSRGs in gastric adenocarcinoma tissues and the survival package was used to screen for CSRGs affecting the prognosis of gastric adenocarcinoma patients in R software.The LASSO regression analysis was used to construct a risk model for gastric adenocarcinoma and calculate the risk score for each patient.The Kaplan-Meier survival analysis was used to compare the overall survival(OS)of patients in high and low risk groups and the validity of prognostic models to predict 5-year survival of patients was analyzed by receiver operator characteristic curve(ROC).Univariate and multivariate Cox regression analyses were used to screen for independent prognostic factors in patients with gastric adenocarcinoma.Gene set enrichment analysis(GSEA)was used to predict potential signaling pathways in patients of high and low risk groups.Based on ESTIMATE and single sample gene set enrichment analysis(ssGSEA)algorithms to analyze the differences in tumor immune micro-environment between high and low risk groups of patients.Results:Sixteen prognostically relevant differentially expressed CSRGs were screened.The prognosis model of the genes containing AGT,EZH2,NOX4 and ZFP36 were constructed by LASSO regression analy-sis,and the patients were divided into two groups of high and low risk according to the median risk score.Survival analysis showed that patients in the high-risk group had significantly lower OS than those in the low-risk group.ROC curve analysis proved the accuracy of the prognostic model to predict the 5-year survival of patients(AUC=0.703).Then multifactorial Cox regression analysis suggested that age and risk score were independent prognostic factors for patients with gastric adenocarcinoma.GSEA enrichment analysis demonstrated that the high-risk group was associated with signaling pathways such as epithelial mesenchymal transition,hypoxia,and angiogenesis,while the low-risk group was associated with signaling pathways such as G2M checkpoint,DNA repair,and peroxisome.Further analy-sis showed that patients in the high-risk group had a higher abundance of immune cell infiltration and higher levels of immune check-point-related gene expression.Conclusion:In this study,a new prognostic model related to cellular senescence in gastric adenocarci-noma was constructed,in which patients in the high-risk group had higher immunoreactivity.

Aim To investigate the role and underlying mechanisms of transient receptor potential cation chan-nel 6(TRPC6)in epileptogenesis using a kainic acid(KA)-induced mouse model.Methods C57BL/6 and TRPC6-KO(KO)mice were divided into two groups and implanted with cannulas for microinjection of KA(0.03 g·L-1,5 μL)into the lateral ventricle to establish the acute epilepsy model group,with saline injection serving as the control group.The Racine score was used to record the uninterrupted seizure grade of mice within two hours after KA administration.Immunohistochemistry was used to detect neuronal loss and tissue damage in the hippocampus brain region of mice.Immunofluorescence staining,Western blot and qPCR were used to detect the expressions of TRPC6,NLRP3,ASC,Caspase-1,p62,Atg7,Atg5,Beclin-1,LC3b-Ⅱ/LC3b-Ⅰ.in the hippocampus.Results KA induced significant neuronal loss and tissue damage in the hippocampal CA3 brain region of epilep-sy mice,while the expression levels of TRPC6,NL-RP3,ASC and Caspase-1 and other proteins in the hippocampus brain area of epilepsy mice increased,and the protein expression of autophagy-related proteins Atg7,Atg5,Beclin-1,LC3b-Ⅱ/LC3b-Ⅰ increased,while the expression of p62 protein decreased.TRPC6 knockout exacerbated KA-induced epileptogenesis,neuronal injury,inflammatory response and autophagy activation.Conclusion TRPC6 is involved in KA-in-duced epileptigenesis,and the mechanism may be re-lated to the activation of NLRP3 inflammasome-autoph-agy signaling caused by TRPC6 deletion.