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:A preliminary trial is conducted to explore whether perioperative(preoperative,intraoperative,and postoperative)electroacupuncture is more effective than postoperative electroacupuncture in improving gastrointestinal function for colorectal cancer patients.Methods and analysis:The study proposes a randomized,parallel-controlled,single-center trial involving 30 colorectal cancer patients aged 18-79 requiring elective surgery.Participants are randomly assigned to two groups,with equal allocation,where one group receives perioperative electroacupuncture,and the other group receives postoperative electroacupuncture.The treatment duration spans from preoperative to postoperative 72 h,with a subsequent 28-day follow-up period.The primary outcome is the time of first postoperative defecation.The secondary outcomes include the recovery time of postoperative bowel sounds,time of the first flatus,dietary recovery,postoperative gastrointestinal dysfunction frequency,quality of life scale,postoperative pain degree,time of the first ambulation,length of hospital stay,gastrointestinal hormone indicators,and adverse events.The coagulation function test,liver and renal function,and stool and blood routine serve as security biomarkers.The statistical analysis includes the t-test,rank-sum test,Chi-square test,and analysis of variance.A two-sided significance level is set at 5%.Discussion:This study aims to evaluate the feasibility and preliminary effectiveness of perioperative electroacupuncture for gastrointestinal function recovery following colorectal cancer surgery.The study's strengths include its randomized design,well-defined intervention periods,and multi-dimensional outcome assessment.Nevertheless,limitations,such as the small sample size and single-center setting,may affect external validity.The findings will guide protocol refinement and sample size estimation for future large-scale multi-center randomized controlled trials.

Objective:A preliminary trial is conducted to explore whether perioperative(preoperative,intraoperative,and postoperative)electroacupuncture is more effective than postoperative electroacupuncture in improving gastrointestinal function for colorectal cancer patients.Methods and analysis:The study proposes a randomized,parallel-controlled,single-center trial involving 30 colorectal cancer patients aged 18-79 requiring elective surgery.Participants are randomly assigned to two groups,with equal allocation,where one group receives perioperative electroacupuncture,and the other group receives postoperative electroacupuncture.The treatment duration spans from preoperative to postoperative 72 h,with a subsequent 28-day follow-up period.The primary outcome is the time of first postoperative defecation.The secondary outcomes include the recovery time of postoperative bowel sounds,time of the first flatus,dietary recovery,postoperative gastrointestinal dysfunction frequency,quality of life scale,postoperative pain degree,time of the first ambulation,length of hospital stay,gastrointestinal hormone indicators,and adverse events.The coagulation function test,liver and renal function,and stool and blood routine serve as security biomarkers.The statistical analysis includes the t-test,rank-sum test,Chi-square test,and analysis of variance.A two-sided significance level is set at 5%.Discussion:This study aims to evaluate the feasibility and preliminary effectiveness of perioperative electroacupuncture for gastrointestinal function recovery following colorectal cancer surgery.The study's strengths include its randomized design,well-defined intervention periods,and multi-dimensional outcome assessment.Nevertheless,limitations,such as the small sample size and single-center setting,may affect external validity.The findings will guide protocol refinement and sample size estimation for future large-scale multi-center randomized controlled trials.

This study was aimed at exploring novel auxiliary diagnostic biomarkers for brucellosis and their potential miR-NA-mRNA regulatory networks.High-throughput sequencing was used to compare miRNA expression differences in serum ex-osomes between patients with brucellosis and healthy controls.Subsequently,RT-qPCR was used to validate the expression of significantly upregulated exosomal miRNAs.The diagnostic value of these miRNAs was assessed with ROC curves,and bioin-formatics analyses were performed to investigate the potential roles of the miRNAs in brucellosis infection.The ROC curve a-nalysis indicated that the area under the curve for exosomal hsa-miR-11400(P＜0.05),hsa-miR-199a-5p(P＜0.05),and hsa-miR-148a-5p(P＜0.05)was 0.79,0.81,and 0.74,respectively.A total of 465 differentially expressed miRNAs and their tar-get genes were predicted,including 25 immune-related target genes,most of which were closely associated with cancer-related proteoglycans,NF-kappa B signaling pathways,and IL-17 signaling pathways.The constructed differentially expressed gene network indicated that the immune genes PLXNA2,IL17RA,PRKCA,CD22,ACVR1B,and CBL might be regulated by hsa-miR-199a-5p and hsa-miR-148a-5p.These findings suggest that exosomal miRNAs might serve as auxiliary diagnostic indicators for brucellosis.Our exosomal miRNA-mRNA regulatory network provides new insights into the pathogenesis and treatment of brucellosis.

This study was aimed at exploring novel auxiliary diagnostic biomarkers for brucellosis and their potential miR-NA-mRNA regulatory networks.High-throughput sequencing was used to compare miRNA expression differences in serum ex-osomes between patients with brucellosis and healthy controls.Subsequently,RT-qPCR was used to validate the expression of significantly upregulated exosomal miRNAs.The diagnostic value of these miRNAs was assessed with ROC curves,and bioin-formatics analyses were performed to investigate the potential roles of the miRNAs in brucellosis infection.The ROC curve a-nalysis indicated that the area under the curve for exosomal hsa-miR-11400(P＜0.05),hsa-miR-199a-5p(P＜0.05),and hsa-miR-148a-5p(P＜0.05)was 0.79,0.81,and 0.74,respectively.A total of 465 differentially expressed miRNAs and their tar-get genes were predicted,including 25 immune-related target genes,most of which were closely associated with cancer-related proteoglycans,NF-kappa B signaling pathways,and IL-17 signaling pathways.The constructed differentially expressed gene network indicated that the immune genes PLXNA2,IL17RA,PRKCA,CD22,ACVR1B,and CBL might be regulated by hsa-miR-199a-5p and hsa-miR-148a-5p.These findings suggest that exosomal miRNAs might serve as auxiliary diagnostic indicators for brucellosis.Our exosomal miRNA-mRNA regulatory network provides new insights into the pathogenesis and treatment of brucellosis.

Aim To systematically investigate the ac-tive components,targets,and regulatory pathways of Po-lygonum capitatum in intervening atherosclerosis(AS)through network pharmacology,molecular docking and animal experiments.Methods Active components of Polygonum capitatum and AS-related targets were screened and identified through database searches.Protein-protein interaction(PPI)network analysis was performed using the STRING database,followed by GO and KEGG enrichment analyses via the David plat-form.Molecular docking validation was conducted with AutoDock.An AS model was established in Syrian golden hamsters fed a high-fat diet.Predicted pathways and targets were validated using qPCR,ELISA,and histopathological assessment of aortic and hepatic tis-sues via HE staining.Results Network pharmacology identified 27 potential active components of Polygonum capitatum(primarily flavonoids such as quercetin and luteolin)and 110 drug-disease intersection targets,in-cluding core targets MMP-9,ALB,and AKT1.GO and KEGG analyses enriched 593 and 125 pathways,re-spectively,with the NF-κB inflammatory pathway,TNF signaling pathway and lipid metabolism/atherosclerosis pathways highlighted as key mechanisms.Animal ex-periments demonstrated that Polygonum capitatum im-proved serum lipid profiles(reduced TC,TG,LDL-C)in AS hamsters,suppressed the MMP-9/NF-κB signa-ling pathway(downregulated MMP-9,p65 phosphoryla-tion,TNF-α,and IL-6),and inhibited VSMC synthetic phenotypic transformation(upregulated α-SMA and myocardin)by downregulating MCPIP1.Additionally,Polygonum capitatum ameliorated aortic lesions and he-patic lipid deposition in AS hamsters.Conclusions Polygonum capitatum alleviates AS by synergistically regulating the MMP-9/NF-κB/MCPIP1 axis through flavonoid components,suppressing vascular inflammato-ry cascades and maintaining VSMC contractile pheno-types.This reflects Polygonum capitatum's multi-com-ponent,multi-pathway,and multi-target characteristics in combating AS.

Objective To explore the feasibility and corresponding implementation methods of constructing a sample resource bank based on individual-level data of completed clinical trials and using it to construct external controls for drug/device clinical trials.Methods Taking the pre-marketing clinical trial of transcatheter active valve replacement(TAVR)for the treatment of aortic valve stenosis as an example,the individual-level databases of multiple trials were standardized to form a sample bank.The original data of any trial in the sample bank were selected as the experimental group,and the remaining samples were selected as the control group.The potential confounding was handled by using the propensity score matching and stratification methods to clarify the process of constructing external controls based on the sample bank of individual-level data of clinical trials.Results This study included individual-level data of single-group trials of 4 TAVR devices,with a total of 569 subjects(59.2%male).The number of subjects in Trials 1 to 4 was 120,120,163,and 166,respectively.Propensity score matching enabled the matching of 113,117,125,and 147 subjects with comparable or similar characteristics from individual-level data from other trials,respectively,demonstrating a high matching success rate.The PS score distribution plot after stratification showed that the proportions of subjects in the experimental and control groups in strata 1 to 5 in scheme 1 were 4/103,11/103,22/92,32/87,and 51/64,respectively.For all constructed external controlled trials,a certain number of control samples with similar baseline characteristics to the experimental groups were distributed within each propensity score stratum.The results of the simulation test also reflected the potential differences between different devices in the 12-month all-cause mortality rate.Conclusions The sample bank constructed with individual-level data from clinical trials,as a high-quality data source,can serve as a source of external control for single-arm trials in the same field,and as a useful supplement to the external control scenario of real-world evidence to support drug and device development.At the same time,targeted research on research methods and bias control measures in related fields is also needed.

Objective:The genotoxicity risk of graphene artificial nerve sheath conduit was systematically evaluated to provide scientific evidence for their clinical safety and to establish methodological references for the genotoxicity assessment of nanomaterial medical devices.Methods:The potential effects of graphene artificial nerve sheath conduit on genetic and chromosomal endpoints were analyzed by integrating bacterial reverse mutation assays,in vitro chromosome aberration assays,mouse lymphoma cell TK gene mutation tests,and mammalian erythrocyte Pig-a gene mutation assays.Results:In the bacterial reverse mutation assay,all plates showed good background growth.There was no significant difference in the average number of revertant colonies between the test group and the negative control group,with a ratio around 1.0.In the in vitro chromosome aberration assay,the chromosomal aberration rate in the test group was less than 5％,showing no significant increase compared to the negative control group.In the mouse lymphoma cell TK gene mutation assay,the mutation frequency in the test group was less than twice that of the negative control group,with no significant difference.In the mammalian erythrocyte Pig-a gene mutation assay,the mutation frequencies of erythrocytes and reticulocytes in the test group were both less than 3× 10-6,showing no significant difference compared to the negative control group.Conclusions:Graphene artificial nerve sheath conduit exhibited no detectable genotoxicity under the tested conditions,the research results can provide reference and guidance for the genotoxicity evaluation of nanomaterial medical devices.

Objective To explore the debridement effects of 3 types of plasma scalpels for the animal model of explosion injury,and to compare them with the steel scalpel and high-frequency electrosurgical scalpel.Methods Firstly,blast wounds were constructed in the right inguinal regions of 9 Landrace pigs by high-pressure gas impact combined with preset metal shrapnel.Secondly,debridement was carried out in experimental groups with wide-,arrow-or needle-type plasma scalpel and in control groups with steel and high-frequency electrisurgical scalpel,with the operating temperature and debridement time recorded during the procedure and trauma specimens analyzed pathologically after the debridement;comparisons were performed among the five types of scalpels in terms of debridement effect,and among the four ones in terms of maximum operating temperature and depth of tissue thermal damage under electrocutaneous cutting and electrocoagulation modes with the steel scalpel excluded because it did not generate any heat.GraphPad Prism 9.5.1 software was used for statistical analysis.Results There were no significant differences in debridement effect found between the three plasma scalpels and the steel and high-frequency electrosurgical scalpels(P＞0.05).The three types of plasma scalpels had the maximum operating temperature lower significantly than that of the high-frequency electrosurgical scalpel during debridement(P＜0.05).Under electrosection and electrocoagulation modes the three plasma scalpels had the depths of tissue thermal damage statistically less than that by the high-frequency electrosurgical scalpel under electrosection and electrocoagulation modes(P＜0.05).The depths of tissue thermal damage by the four scalpels under electrocoagulation mode were obviously greater than those under electrosection mode(P＜0.05).Conclusion Multi shapes of plasma scalpels behave well in debridement with low operating temperature,little tissue thermal damage and high efficiency for wound protection and the same efficacy with the steel scalpel and high-frequency electrosur-gical scalpel.[Chinese Medical Equipment Journal,2025,46(2):31-38]

Objective:To construct a key item checklist for the Mini-HTA report specification,providing scientific guidance for drafting each section of Mini-HTA research reports,enhancing their standardization,scientific rigor,and completeness,thereby improving the efficiency and quality of health decision-making.Methods:Based on preliminary literature review and qualitative systematic review,a pool of problem items for the Mini-HTA report specification was formed.Delphi questionnaires were distributed,and the Delphi technique was employed through two rounds of expert consultation to optimize and select key items.Results:Through two rounds of Delphi expert consultation,the initial Mini-HTA report specification item checklist was screened,integrated,and supplemented.A finalized key item checklist was constructed,comprising 8 first-level items(Title,Abstract,Introduction,Methods,Results,Discussion,Conclusion,and Other Relevant Information)and 48 second-level items.Conclusion:The constructed key item checklist for the Mini-HTA report specification provides scientific guidance for drafting Mini-HTA research reports.It helps enhance the standardization and transparency of the assessment process and the reliability of results,thereby optimizing the efficiency and quality of health decision-making.