SMYD5 is a ribosomal methyltransferase with SET and MYND structural domains， which is a member of the SMYD family and is expressed in a variety of tissues， including ovary and testis. This enzyme participates in biological processes such as gene expression regulation， cell development and differentiation， and maintenance of genomic stability through ribosomal protein methylation modification. In recent years， research on SMYD5 has increased in cancers including hepatocellular carcinoma， gastric adenocarcinoma， and lung cancer. Studies have revealed that SMYD5 exhibits high expression levels in various diseases including hepatocellular carcinoma， gastric adenocarcinoma， lung cancer， and inflammatory bowel disease， influencing the progression of these conditions. This review summarizes the role of SMYD5 in hepatocellular carcinoma， inflammatory bowel disease， and other biological functions， aiming to provide a reference for related disease research.

In-depth study of the components of polymyxins is the key to controlling the quality of this class of antibiotics.Similarities and variations of components present significant analytical challenges.A two-dimensional(2D)liquid chromatography-mass spectrometry(LC-MS)method was established for screening and comprehensive profiling of compositions of the antibiotic colistimethate sodium(CMS).A high concentration of phosphate buffer mobile phase was used in the first-dimensional LC system to get the components well separated.For efficient and high-accuracy screening of CMS,a targeted method based on a self-constructed high resolution(HR)mass spectrum database of CMS components was established.The database was built based on the commercial MassHunter Personal Compound Database and Library(PCDL)software and its accuracy of the compound matching result was verified with six known components before being applied to genuine sample screening.On this basis,the unknown peaks in the CMS chromatograms were deduced and assigned.The molecular formula,group composition,and origins of a total of 99 compounds,of which the combined area percentage accounted for more than 95％of CMS components,were deduced by this 2D-LC-MS method combined with the MassHunter PCDL.This profiling method was highly efficient and could distinguish hundreds of components within 3 h,providing reliable results for quality control of this kind of complex drugs.

Objective To draw the genome-wide distribution and remodeling characteristics of H3K27me3 silencers in signet-ring cell carcinoma of the stomach(SRCC)through epigenetic sequencing technology,and to investigate their roles in transcriptional regulation in order to elucidate the regulatory mechanism of SRCC malignant progression.Methods The study was conducted on 35 gastric samples obtained by gastroendoscopic biopsy(15 normal and 20 SRCC tissues)from Department of Gastroenterology of Army Medical Center of PLA between January 2021 and December 2023.Multi-omics analyses,including assay for transposase-accessible chromatin with high-throughput sequencing(ATAC-seq),cleavage under targets and tagmentation(CUT&Tag)and transcriptome sequencing(RNA-seq),were performed to identify chromatin accessibility,H3K27me3 silencer regions,and transcriptional changes,with aid of Illumina NovaSeq 6000.H3K27me3 related differentially expressed genes(|Log2FC|>1,FDR<0.05)were screened using DESeq2.Gene Ontology(GO)analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)analysis were employed to analyze the enrichment function,and Homer was employed to identify transcription factor motifs.A regulatory network was constructed using Cytoscape,and then validated using immunohistochemistry to explore its regulatory mechanism.Results H3K27me3 silencers were primarily located in distal intergenic regions(37.06%)in SRCC.Compared with the normal tissues,SRCC showed a significant reduction in H3K27me3 silencer signals(95%CI:1.34～2.30,P=0.007)with 6 257 lost sites(FDR<0.01).Integrating CUT&Tag and RNA-seq revealed 380 up-regulated immune-related genes,particularly in T cell receptor signaling(OR=4.2,95%CI:2.8～6.3,P=0.002).Immunohistochemistry confirmed elevated expression of transcription factor EHF(P<0.05).Conclusion There is the remodeling of H3K27me3 silencers in SRCC,and EHF may potentially play a crucial role in the SRCC malignant progression.

Objective To identify the enhancer profile marked by histone H3K27ac modification in high-grade intraepithelial neoplasia(HGIN)in order to reveal the novel regulatory mechanism of HGIN pathogensis.Methods Gastric tissue samples were collected from Department of Gastroenterology of Army Medical Center of PLA between June 2022 and June 2023,including 14 normal gastric tissues(Nor group),31 HGIN tissues(HGIN group)and 17 gastric cancer tissues(GC group).Cleavage under targets and tagmentation(CUT&Tag)technique was employed to capture enhancer regions modified by histone H3K27ac.Multi-omics analysis was performed to identify HGIN-specific active enhancers and their potentially regulated genes.Immunohistochemical profiling was performed to assess differential expression of the gene of interest across clinically stratified specimens,combined with CRISPR-dCas9-mediated ablation of active enhancers to monitor the gene of interest transcriptional dynamics and validate enhancer-mediated regulatory mechanisms.Results Epigenomic sequencing obtained the data with excellent quality,and indicated that obvious remodeling was observed in H3K27ac enhancers in HGIN and GC groups(P<0.05),though no significant difference in the genome-wide distribution of H3K27ac modification among the 3 groups.Combining transcriptome data revealed that enhancer remodeling may up-regulate the expression of the proliferation-related target gene,CD24,in the HGIN tissue;while,inhibiting enhancer activity can notably reduce CD24 expression level(P<0.05).Immunohistochemical assay displayed a positive correlation between the expression levels of CD24 and Ki-67(P<0.001).Conclusion The remodeling of H3K27ac enhancer represents a significant epigenetic feature of the transformation from normal condition to HGIN.Remodeling of H3K27ac enhancer up-regulates CD24,which may facilitate the abnormal proliferation of gastric epithelial cells.

Objective To analyze clinical characteristics of mesenchymal-subtype gastric cancer(Mes-GC)by integrating multi-omics data and explore the characteristics of tumor cells and microenvironment associated with the risk for recurrence.Methods Gastric tumor tissue samples were collected from the patients who visited Department of Gastroenterology of Army Medical Center of PLA from January 2022 to December 2023.Transcriptome and genome sequencing were applied for these tissue samples,including 19 cases of diffuse-type gastric cancer,22 cases of intestinal-type gastric cancer,and 23 cases of mixed-type gastric cancer patients.Bioinformatics analysis was employed to investigate the differences in clinical characteristics and tumor microenvironment between Mes-GC and non-mesenchymal-subtype gastric cancer(non-Mes-GC)by integrating data resources including The Cancer Genome Atlas(TCGA),Gene Expression Omnibus(GEO),and National Genomics Data Center(NGDC).Results Compared to non-Mes-GC patients,Mes-GC ones were characterized by later clinical stages,deeper tumor infiltration,and higher rates of lymph node metastasis.Kaplan-Meier survival analysis confirmed that Mes-GC patients were associated with shorter survival time,poor prognosis as well as increased risk of cancer recurrence(P<0.05).Single-cell RNA sequencing data revealed that tumor cells in Mes-GC showed higher expression levels of the genes related to stemness,metastasis(P<0.05),and epithelial-mesenchymal transition(EMT).And in the tumor microenvironment,there were significant more myeloid cells,smooth muscle cells,endothelial cells and fibroblasts,with the most pronounced elevation in the proportion of fibroblasts(P<0.05).Moreover,the patients with larger proportion of fibroblasts were associated with poorer prognosis.Conclusion Mes-GC tumor cells exhibit higher stemness and EMT characteristics,and stromal cells such as myeloid cells,endothelial cells,and fibroblasts are enriched in the tumor microenvironment.These features may be key factors contributing to poor prognosis and high recurrence rate of Mes-GC.

Objective To develop a machine learning-based risk prediction model for postoperative acute kidney injury(AKI)and a model for mortality in obese patients admitted to intensive care unit(ICU)in order to improve early warning and prognostic evaluation to support clinical decision-making.Methods Data of obese postoperative ICU patients were retrospectively retrieved from the MIMIC-Ⅳ and eICU databases for statistical analysis.Ultimately,2 520 patients(670 from MIMIC-Ⅳ and 1 850 from eICU databases)were included to build the risk prediction models for AKI and mortality.The data included demographic information,vital signs,laboratory findings,surgical types,comorbidities,and medication use.After data cleaning and preprocessing,Boruta feature selection was applied,followed by the construction of prediction models using 7 machine learning algorithms,that is,Gradient Boosting Machine(GBM),Generalized Linear Model(GLM),k-Nearest Neighbors(KNN),Na?ve Bayes(NB),Neural Network(NNET),Support Vector Machine(SVM),and XGBoost.Model performance was evaluated through cross-validation and external validation.Results In the risk prediction models of AKI,the SVM model achieved the highest AUC value of 0.80 in the testing set and 0.71 in the external validation test.For the risk prediction models of mortality,the GBM model outperformed others in the prediction,attaining an AUC value of 0.91 in the testing set.Conclusion Risk predictive models for postoperative AKI and mortality in obese ICU patients are successfully constructed,and are valuable tools for clinicians to optimize early intervention and improve clinical outcomes for the patients.

Objective To identify the enhancer landscape marked by histone H3K27ac modifications in diffuse-type gastric cancer(DGC)tissues,and to elucidate the epigenetic remodeling mechanisms by which active enhancers regulate cachexia-related genes.Methods Gastric mucosal tissue samples were collected from Department of Gastroenterology of Army Medical Center of PLA during January 2022 to March 2023,including 10 normal gastric mucosa tissues(Normal group),10 DGC tissues diagnosed with cachexia(DGC group),and 10 organoids derived from DGC tissues(Organoid group).Using H3K27ac chromatin targeting cleavage and tagmentation(CUT&Tag)technology,genomic modification regions were captured to screen specific active enhancers and their potential target genes in DGC tissues.CRISPR-dCas9 gene editing technology was used to intervene with the enhancers,and the expression of target genes was detected with Western blotting and qRT-PCR.Sixteen female SPF-grade BALB/c Nude mice(6～8 weeks old,weighing 18～21 g)were utilized to establish an orthotopic xenograft tumor model using the human diffuse-type gastric cancer cell line MKN45.Cachexia-related phenotypes were evaluated in 3 groups:normal group(n=4),silencing group(n=6),and control group(n=6).Results Significant differential enhancer regions were identified between DGC and normal gastric mucosa tissues.DGC tissues exhibited a marked increase in enhancer abundance(P<0.05)and signal intensity when compared with the normal counterparts.Integrated analysis of transcriptome data revealed that some of these active enhancers up-regulated the expression of GDF15,a cachexia-associated target gene in DGC.Targeted silencing of the active enhancer of GDF15 using CRISPR/dCas9-KRAB plasmid technology resulted in a significant reduction in GDF15 expression at both mRNA levels(P<0.05)and protein.Results from orthotopic transplantation experiments of DGC demonstrated that silencing of active enhancers alleviated the cachexia phenotype in nude mice(P<0.05).Conclusion DGC exhibits enhancer remodeling,which regulates the expression of the cachexia-associated gene GDF15,and thereby contributes to the pathogenesis and progression of cancer cachexia.

Bongkrekic acid(BA)is a toxin with stable properties and no distinctive smell.It exists in common foods such as fermented edible grain products,potato products,spoiled tremella fuciformis and auricularia polytricha,as well as auricularia polytricha that has been soaked too long.It can easily cause food poisoning.At present,there is still a lack of complete method to detect BA,and no spe-cific antidote of BA has been found.Therefore,BA poisoning is easy to be misdiagnosed or missed diagnosed,and its mortality rate remains high.In recent years,studies have revealed the toxic mecha-nism of BA and found that BA can inactivate some enzymes containing thiol groups(-SH)and in-hibit the synthesis and transport of adenosine triphosphate(ATP),causing damage to liver,kidney,brain and other parenchymal organs.This article reviews the autopsy cases and literature of deaths caused by BA poisoning at home and abroad,systematically summarizes the epidemiology,clinical manifestations,pathological changes,toxicological mechanisms,detection methods,forensic diagnostic key points and challenges of BA in forensic medicine,with the aim of providing a reference for foren-sic identification of related cases.

Objective:To evaluate the clinical effectiveness of high tibial osteotomy (HTO) assisted by digital orthopedic techniques in the treatment of varus knee osteoarthritis secondary to tibial fracture malunion.Methods:The clinical data were retrospectively analyzed of the 16 patients who had been admitted to Clinical Application Center of Digital Orthopedic Technology, Tianjin Hospital for varus knee osteoarthritis secondary to tibial fracture malunion from April 2022 to October 2023. There were 6 men and 10 women, with an age of (56.3±1.6) years and a mean body mass index of (23.8±0.9) kg/m 2. HTO was performed for all the patients using patient-specific instrumentation integrated osteotomy and orthopedic guide which was designed and printed with digital orthopedic techniques. If preoperative imaging indicated symptomatic meniscus injury (tear), intraarticular free body, or intercondylar fossa stenosis in a patient, arthroscopic clearance was first conducted before subsequent performance of HTO at one stage. Clinical effectiveness was evaluated by measuring and comparing hip-knee-ankle angle (HKA), medial proximal tibial angle (MPTA), posterior tibial slope (PTS), lower limb weight-bearing line (WBL) ratio, Western Ontario and McMaster University (WOMAC) osteoarthritis index, visual analogue scale (VAS) pain score and knee range of motion (ROM) before surgery and 12 months after surgery. Results:The operative time was (41.3±2.1) min and intraoperative fluoroscopy was performed only once in all the patients. All the wounds healed by the first stage with no such complications as hinge point fracture, wound infection, vascular injury, nerve injury, delayed union or nonunion of fracture, lower limb deep venous thrombosis, loosening of internal fixation, or plate rupture. The follow-up time for the 16 patients was (16.3±0.7) months. At 12 months after surgery, the HKA (179.5°±0.5°), MPTA (91.7°±0.5°), WBL ratio (61.2%±0.4%), WOMAC osteoarthritis index [(12.8±0.8) points], VAS pain score [(1.8±0.3) points] and knee ROM (121.8°±1.8°) were significantly better than those before surgery [166.6°±1.3°, 81.8°±0.4°, 29.6%±1.0%, (38.4±2.1) points, (4.8±0.3) points, and 110.5°±2.1°] ( P < 0.05). There was no significant difference in PTS between pre-surgery and 12 months after surgery ( P > 0.05). Conclusions:When HTO is used to treat varus knee osteoarthritis secondary to tibial fracture malunion, assistance of digital orthopedic techniques can improve HKA, MPTA, lower limb alignment, and knee ROM to reduce and recover knee function for the patients.

Objective:To evaluate the clinical effect of derotational distal femoral osteotomy (DDFO) combined with medial patellofemoral ligament (MPFL) reconstruction assisted by digital orthopedic technique in the treatment of recurrent patellar dislocation with enlarged femoral anteversion angle (FAA).Methods:TThe clinical data of 18 patients (4 men and 14 women; mean age 22.1±0.7 years; range, 18-26 years) with recurrent patellar dislocation (FAA≥30°) admitted to Digital Orthopedic Technology Clinical Application Center in Tianjin hospital from May 2022 to December 2023 were retrospectively analyzed. The average number of patella dislocations were 3.6±0.4 (range, 2-8 times), with a mean symptom duration of 4.3±0.4 years (range, 2-7 years). According to Dejour classification of femoral trochlea dysplasia, there were 5 cases of type A, 3 cases of type B, 6 cases of type C and 4 cases of type D. All patients underwent 3D CT scanning and digital modeling before operation. Based on the modeling results, personalized osteotomy and orthopedic integration guide were designed and printed to direct intraoperative DDFO and MPFL reconstruction. Radiological parameters, knee function and complications were assessed during follow-up. Knee function assessments included visual analogue scale (VAS), Intemational Knee Documentation Committee Knee Form (IKDC), Kujala, Lysholm and Tegner score. The radiological parameters included FAA, patellar tilt angle (PTA), tibial tuberosity-trochlear groove distance (TT-TG) and caton-deschamps index (CDI).Results:All patients underwent surgery and were followed up for 15.4±2.8 months (range, 12-20 months). Complications occurred in 3 patients, including deep venous thrombosis in 2 cases and wound effusion in 1 case. No other complications such as wound infection, nerve injury, vascular injury, fracture nonunion or patella dislocation were recorded. The VAS score improved from 5.4±0.3 preoperatively to 2.1±0.2 at one year postoperatively. The IKDC score improved from 44.4±2.7 to 79.2±1.9 points. The Kujala score improved from 51.8±2.6 to 86.1±1.6, the Lysholm from 49.8±2.5 to 84.9±1.5, and the Tegner score from 2.2±0.2 to 4.1±0.2. The FAA decreased from 39.7°±1.2° to 14.9°±0.2°, the PTA from 33.1°±2.6° to 12.6°±1.4°, and the TT-TG from 20.2±0.6 to 13.9±0.4 mm. The differences between time of all the above-mentioned parameters were statistically significant ( P<0.05). The CDI remained stable, which changed from 1.03±0.02 preoperatively to 1.07±0.01 one year after operation ( P>0.05). Conclusions:After the application of DDFO combined with MPFL reconstruction assist by personalized osteotomy and orthopedic integrated guide, the patient's knee function and imaging parameters were significantly improved at one-year follow-up. In the treatment of recurrent patellar dislocation with enlarged FAA, good early clinical efficacy could be achieved with this operation.