ObjectiveTo evaluate the antitumor activity of Periplaneta americana extract（PAE） against human-derived lung adenocarcinoma organoids（LUAD-PDOs） and to elucidate its potential mechanism based on transcriptomics. MethodsFresh tumor and adjacent normal tissues from patients with LUAD were collected to construct LUAD-PDOs and normal lung organoid（Nor-PDOs） models using 3D organoid culture technology. The effective intervention concentration of PAE was determined using the cell counting kit-8（CCK-8） assay. Experimental groups included the model group（LUAD-PDOs）， normal group， model administration group（LUAD-PDOs+PAE）， and normal administration group（Nor-PDOs+PAE）. Hematoxylin-eosin（HE） staining was used to observe the pathological structures of PDOs， immunohistochemistry（IHC） was performed to detect the expressions of the proliferation marker Ki-67 and lung adenocarcinoma differentiation markers cytokeratin-7（CK-7） and Napsin A， TUNEL staining was applied to detect cell apoptosis. RNA sequencing（RNA-Seq） was conducted to identify differentially expressed genes（DEGs）， followed by Gene Ontology（GO）， Kyoto Encyclopedia of Genes and Genomes（KEGG）， and Gene Set Enrichment Analysis（GSEA）， alongside protein-protein interaction（PPI） network analysis to screen core mechanisms. Finally， key targets were validated by integrating external database analysis with immunofluorescence（IF）. ResultsNor-PDOs and LUAD-PDOs that highly recapitulated the pathological characteristics of the primary tissues were successfully established. The CCK-8 assay determined that the effective intervention concentration of PAE was 16 g·L^-1. Morphological observation showed that Nor-PDOs exhibited lumen-forming structures， whereas LUAD-PDOs displayed dense， solid structures. CCK-8 and TUNEL assays revealed that， compared with the model group， PAE intervention inhibited the proliferation of LUAD-PDOs and promoted apoptosis in LUAD cells， while showing no significant effect on the viability of Nor-PDOs. Transcriptomic analysis identified 719 DEGs that were significantly reversed after PAE intervention（347 up-regulated and 372 down-regulated）（P<0.05）. GO enrichment analysis indicated that DEGs in the model administration group were significantly enriched in biological processes related to cell cycle regulation compared to the model group. KEGG pathway analysis revealed that PAE affected pathways related to proliferation and metabolism， including pathways in cancer and the p53 signaling pathway. GSEA further confirmed that PAE significantly enhanced the activity of the p53 signaling pathway（P<0.05）. PPI network analysis indicated that breast cancer type 1 susceptibility protein（BRCA1） and checkpoint kinase 1（CHEK1） were the core down-regulated targets in the p53 pathway. IF verified the high expression of BRCA1 and CHEK1 in LUAD-PDOs and their significant downregulation after PAE intervention（P<0.05）. Furthermore， survival analysis based on The Cancer Genome Atlas（TCGA） database indicated that low expression of BRCA1 and CHEK1 was significantly associated with prolonged overall survival in patients with LUAD（P<0.05）. ConclusionPAE effectively inhibits proliferation of LUAD-PDOs and promotes their apoptosis， its anti-tumor mechanism is potentially associated with the activation of the p53 signaling pathway， with BRCA1 and CHEK1 genes likely serving as key downstream targets for the effects of PAE.

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.

OBJECTIVE To quantitatively assess the compatibility risk of commonly used intravenous drugs in intensive care unit （ICU） patients with severe pneumonia， and provide a reference for reducing the incidence of adverse events caused by incompatibility. METHODS The PASS clinical pharmacy management system was used to retrospectively collect the data of patients diagnosed with “severe pneumonia” in the ICU of Hebei General Hospital from January 2023 to June 2025， and the commonly used intravenous drugs and medication frequency were extracted. Based on authoritative databases such as Micromedex and Stabilis as well as relevant literature， the compatibility data of commonly used intravenous drugs with 0.9% Sodium chloride injection and 5% Glucose injection were summarized. The theoretical and actual compatibility risk values were calculated using formulas， and high-risk drugs were screened and the compatibility query table was drawn. RESULTS A total of 158 ICU patients with severe pneumonia were treated with 89 intravenous drugs， and 24 drugs with high compatibility risk were identified. The drug with the highest theoretical compatibility risk value was Amphotericin B for injection （risk value 146）， and the drug with the highest actual compatibility risk value was Propofol medium and long chain fat emulsion injection （risk value 8 740）. Among the 24 high-risk drugs， six drugs， namely Esomeprazole sodium for injection， Ambroxol hydrochloride injection， Midazolam injection， Methylprednisolone sodium succinate for injection， Furosemide injection， and Cefoperazone sodium and sulbactam sodium for injection， simultaneously ranked among the top 15 in both theoretical and actual compatibility risk rankings. Among 650 pairwise compatibility combinations of the 24 drugs， 24.62% were compatible， 11.23% were incompatible， 6.77% had conflicting evidence， and 57.38% had missing evidence. CONCLUSIONS This study quantitatively analyzed the medication safety of commonly used intravenous drugs in ICU patients with severe pneumonia， identified 24 drugs with high compatibility risk， and established a compatibility query table for high-risk drugs， which helps reduce the risk of ICU compatibility adverse events.

Metabolic dysfunction-associated fatty liver disease （MAFLD） has become the most common chronic liver disease worldwide. Its pathological process is centered on the “two-hit” theory， with gut-liver axis dysregulation running through the entire disease course from steatosis to liver cirrhosis and even hepatocellular carcinoma， and it forms an extensive cross-system regulatory mechanism with the metabolic， cardiovascular， renal， and psychological and nervous systems through multi-dimensional pathways such as the “gut-liver-brain axis”， the “liver-kidney axis”， and the “liver-heart axis”. Disease progression is not limited to the liver itself， and it also involves functional imbalance of multiple organ systems throughout the body. This article systematically elaborates on the association mechanism of “liver pathological progression-multi-axis regulation-comorbidity occurrence” in MAFLD， proposes synergistic management strategies integrating early screening based on risk stratification， targeted intervention， and multidisciplinary diagnosis and treatment， and analyzes the limitations of current research and future development directions， in order to provide a theoretical basis and practical guidance for precise diagnosis and treatment and individualized management of MAFLD.

In recent years,significant breakthroughs have been achieved in the immunotherapy for Alzheimer's disease.In line with global advancements,two anti-amyloid-β monoclonal antibodies have been approved and successfully launched in China for clinical use.Lecanemab and Donanemab were officially used in June 2024 and April 2025 in China,respectively.In order to standardize the rational and safe application of anti-amyloid-β monoclonal antibodies for Alzheimer's disease in China,this article integrates recom-mendations from the clinical trials and real-world experience from the author's team and domestic peers to further update the recom-mendations for the clinical use of anti-amyloid-β monoclonal antibody based on the 2024 version.It includes indications for therapy,pre-treatment evaluation and preparation,administration protocols and safety measures during treatment,and post-treatment monitor-ing strategies.

As a new generation of time-of-flight mass spectrometry,multiple-reflection time-of-flight mass spectrometry(MR-TOF-MS)has been increasingly applied in the fields such as nuclear physics,chemistry,and biology due to its ultra-high resolution and rapid analysis capabilities.However,the analytical performance of MR-TOF-MS largely depends on the ion bunch state entering the mass analyzer.In this study,a rectangular ion trap(RIT)was developed,designed and processed using printed circuit board technology,as an ion accumulating and focusing device for MR-TOF mass analyzer.Compared to traditional ion traps composed of two sets of planar electrodes,this RIT had higher voltage utilization efficiency,resulting in more efficient ion collection and focusing.The ions were cooled to a sufficiently small bunch for precise mass measurement with MR-TOF-MS mass spectrometry in only 1 ms of cooling time in the RIT,then orthogonally ejected to the MR-TOF mass spectrometer for mass analysis.Experimental results indicated that the working cycle,ion flux,and ion focusing state of the RIT fully met the requirements of the MR-TOF mass analyzer.When coupled with the MR-TOF mass analyzer,the RIT enabled MR-TOF-MS to achieve a mass resolution of 1.5×105.

Background and aims:Studies indicate that the gut microbiota and its metabolites are involved in the progression of cardiovascular diseases,and enterohepatic circulation plays an important role in this progression.This study aims to identify potential probiotics for the treatment of unstable angina(UA)and elucidate their mechanisms of action.Methods:Initially,the gut microbiota from patients with UA and control was analyzed.To directly assess the effects of Bifidobacterium supplementation,10 patients with UA were enrolled and administered Bifidobacterium(630 mg per intake twice a day for 1 month).The fecal metagenome,serum trimethyl-amine N-oxide(TMAO)levels,and other laboratory parameters were evaluated before and after Bifido-bacterium supplementation.Results:After supplementing with Bifidobacterium for 1 month,there were statistically significant dif-ferences(P＜0.05)in TMAO,aspartate aminotransferase,total cholesterol,and low-density lipoprotein compared to before.Additionally,the abundance of Bifidobacterium longum increased significantly,although the overall abundance of Bifidobacterium did not reach statistical significance.The gut micro-biota,metabolites,and gut-liver axis are involved in the progression of UA,and potential mechanisms should be further studied.Conclusions:Metagenomic analysis demonstrated a reduced abundance of Bifidobacterium in patients with UA.Supplementation with Bifidobacterium restored gut dysbiosis and decreased circulating TMAO levels in patients with UA.This study provides evidence that Bifidobacterium may exert cardiovascular-protective effects through the gut-liver-heart axis.

[Objective] To explore the accuracy and feasibility of non-invasive prenatal diagnosis of fetal RhE genotype using cell-free fetal DNA (cff-DNA) from maternal peripheral blood. [Methods] A total of 134 pregnant women with single fetuses and RhE-negative blood group were selected from our hospital from November 2023 to August 2024. Free DNA extraction kit was used to extract free DNA from peripheral blood of pregnant women, and the RhE blood group genotype of free DNA was detected by real-time fluorescent quantitative PCR (RT-qPCR). If the qPCR amplification signal of the sample was negative, the methylated RASSF1A gene was amplified, and the positive amplification result was used as a sign of successful extraction of cff-DNA. Serological microcolumn gel method was used to detect the phenotype of RhE blood group in neonatal peripheral blood. [Results] Among the 134 maternal peripheral blood samples, the cff-DNA detection of RhE blood group phenotypes was consistent with the RhE blood group genotyping of neonatal peripheral blood in 133 cases, including 90 cases of Rhee genotype and 43 cases of RhE genotype, with diagnostic concordance rate of 99.3%, sensitivity of 97.7%, specificity of 100%, youden index of 0.977, area under ROC curve of 0.995, the Kappa value of 0.983, positive predictive value of 100%, and negative predictive value of 98.9%. The sample of 1 case failed to be detected. After the amplification of methylated RASSFIA gene, it was confirmed that the reason for the failure was that no cff-DNA was extracted from the sample. The diagnostic concordance rates of the first, second and third trimesters were 93.8% (15/16), 100% (51/51) and 100% (67/67), respectively. Fisher's exact test method was used to calculate the P value, which was P>0.05, indicating that there was no statistical significance in the difference of diagnostic concordance rate among the three pregnancy periods, and there was no difference in the detection concordance rate of this method in different pregnancy periods. [Conclusion] The use of cff-DNA in maternal peripheral blood for the detection of fetal RhE blood group genotype is an accurate and highly feasible non-invasive prenatal diagnostic method, which is helpful for the clinical diagnosis of fetal and neonatal hemolytic disease caused by anti-E antibody.

Objective To investigate the expression of ferritinophagy-related gene ELAV-like RNA binding protein 1(ELAVL1)in multiple myeloma(MM)and elucidate its diagnostic and prognostic value for MM.Methods First,we analyzed ELAVL1 expression level in healthy controls and MM patients using data from the GEO and TCGA databases.Subsequently,bone marrow specimens were collected from 28 newly diagnosed MM patients and 20 healthy controls,and qRT-PCR was employed to validate ELAVL1 expression.The diagnostic and prognostic potential of ELAVL1 was assessed using ROC curve analysis and Kaplan-Meier survival curves.Additionally,univariate and multivariate COX regression analyses were performed to identify independent risk factors for MM prognosis.Finally,KEGG and GO enrichment analyses were performed using the DAVID online platform.Results The level of ELAVL1 expression was significantly higher in newly diagnosed MM patients and refractory/relapsed MM patients than in the healthy controls(P＜0.001).Moreover,ELAVL1 expression was positively correlated with the International Staging System(ISS)stage of MM(P＜0.01).Furthermore,qRT-PCR validation confirmed that ELAVL1 expression was elevated in the 28 newly diagnosed MM patients compared to the 20 healthy controls(P＜0.001).ROC curve analysis demonstrated that ELAVL1 could effectively differentiate between newly diagnosed MM patients,healthy controls,and MGUS patients(P＜0.001 and P=0.000 2,respectively).Survival analysis revealed that high ELAVL1 expression was associated with shorter progression-free survival(P=0.0141)and overall survival(P=0.008 0).Univariate and multivariate COX regression analyses identified high ELAVL1 expression as an independent risk factor for poor MM prognosis(P=0.005 0).KEGG analysis suggested that ELAVL1 might be involved in the Hippo and MAPK signaling pathways.Conclusion High ELAVL1 expression in MM may serve as a biomarker for diagnosis and poor prognosis.ELAVL1 may promote MM initiation and progression via the Hippo and MAPK signaling pathways.

This paper uses literature and network data to systematically sort out the theoretical and practical foundations of global public health cooperation,combines expert interviews to conduct empirical analyses,and further explores China's strategies for participating in global public health cooperation through quantitative statistics and text mining of interview data,and proposes a plan for China's participation in global public health cooperation under the current international situation.Under the countercurrents to globalization,China should take its own public health capacity building as the foundation,put global security and health equity at the core,with a philosophy of open cooperation and sustainable development,actively promote bilateral and multilateral cooperation,focus on cultivating global health talents,and enhance the effectiveness of disease prevention and control by making use of existing platforms,international mechanisms and digital health technologies,so as to help build a Global Community of Health for All.