Background: High-mobility group box protein 1 (HMGB1) is a chromatin-binding protein involved in arthritis, ischemia, sepsis, atherosclerosis, neurodegenerative disorders, meningitis, and cancer. HMGB1 exhibits dual roles in cancer, acting as either a tumor suppressor or oncoprotein depending on context. Objective: This research aimed to elucidate HMGB1’s functional significance in cutaneous squamous cell carcinoma (cSCC). Methods: We overexpressed HMGB1 in cSCC cell lines using recombinant adenovirus and examined its effects on cell proliferation, colony formation, and cell migration. Results: Immunohistochemical analysis revealed elevated HMGB1 expression levels in cSCC tissue relative to normal epidermis. To assess the influence of HMGB1, we employed recombinant adenoviruses expressing HMGB1 to transduce SCC cell lines (SCC12 and SCC13). Enhanced HMGB1 expression significantly promoted cellular proliferation and colony formation capacity.Notably, HMGB1 overexpression elevated the levels of proliferation regulators, including P63, SOX2, CDK4 and CDK6. Furthermore, HMGB1 overexpression substantially enhanced tumor invasiveness, accompanied by upregulation of epithelial-mesenchymal transition (EMT) biomarkers. Mechanistically, overexpression of HMGB1 enhanced transforming growth factor-β signaling by increasing phosphorylation of SMAD2/3, the key mediators of EMT. Conclusion These data imply that HMGB1 acts as a tumor-promoting factor in cSCC.

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 investigate the role and signaling pathway mechanism of Orosomucoid-1（ORM1）in hepatocyte proliferation. Methods The expression data of ORM1 after liver resection from the GEO database were analyzed. The effects of ORM1 on hepatocyte proliferation were assessed after overexpressing ORM1 or supplementing exogenous ORM1 in liver cells. Cell proliferation was evaluated by the CCK8 assay. RNA sequencing （RNA-seq） was performed on liver tissues from ORM1 knockout mice and wildtype littermates to analyze gene expression, and KEGG enrichment analysis was employed to explore the molecular mechanisms by which ORM1 regulates hepatocyte proliferation. Results After partial liver resection in mice, ORM1 expression increased during the liver regeneration process. In vitro, ORM1 promoted the proliferation of murine Hepa1-6 hepatocytes and human HepG2 hepatocellular carcinoma cells. RNA-seq analysis of liver tissues from ORM1 knockout mice indicated that ORM1 influenced several proliferation-related pathways, including the PI3K-Akt, MAPK, Hippo, and Jak-Stat pathways. Upon ORM1 knockout, the expression of pro-proliferative genes such as Ctgf, Tcf7, Tead1, Il6ra, and Lepr decreased, while the expression of anti-proliferative genes such as Cish and Gadd45a increased. Conclusion ORM1 may promote hepatocyte proliferation by regulating key genes in cell proliferation-related pathways, including the PI3K-Akt, MAPK, Hippo and Jak-Stat pathways.

Objective:To evaluate the efficacy of multimodal prehabilitation in patients with refractory functional constipation undergoing Jinling procedure(modified Duhamel surgery).Methods:In this prospective randomized controlled trial,80 patients with refractory functional constipation scheduled for Jinling procedure at the Department of General Surgery,the General Hospital of Eastern Theater Command between January 2020 and December 2021 were enrolled.Participants were randomly assigned to either the observation group(n=40,multimodal prehabilitation)or control group(n=40,routine nursing care).Outcome measures included:time to first flatus,time to first ambulation,defecation volume on postoperative day 5,length of hospitalization,nutritional markers(hemoglobin,albumin,total protein at postoperative day 7),anxiety/depression scores(Hospital Anxiety and Depression Scale,HADS),and total complication rates.Results:Compared to controls,the first ventilation time(48.02±6.15)h,first ambulation time(49.92±5.58)h,defecation volume on the fifth day(234.50±51.03)mL,hospital stay(13.15±2.64)d,anxiety score(43.68±3.45)points,depression score(43.81±1.58)points,and the total incidence of postoperative complications(15%)were significantly lower in the observation group(all p values<0.05).By contrast,the serum levels of hemoglobin(115.60±11.60)g/l,albumin(41.19±5.79)g/L and total protein(61.64±4.94)g/L on day 7 post-operatively were significantly higher in the observation group than those in the control group(P<0.05).Conclusions:Multimodal prehabilitation enhances postoperative intestinal recovery,reduces complications,improves nutritional status,and shortens hospital stays in refractory functional constipation patients undergoing Jinling procedure,supporting its clinical adoption.

Objective To investigate the differential expression genes(DEGs)related to angiogenesis in rosacea(RA)by utilizing bioinformatics analysis in order to screen the key genes and verify their mRNA expression levels.Methods The gene microarray dataset GSE65914 was retrieved from the Gene Expression Omnibus(GEO)repository.Analyzed by R programming,the dataset was refined to identify DEGs related to RA,and then cross-referenced with angiogenesis-related genes from the GeneCards database to get a subset specific to RA angiogenesis.The process of identifying key genes was augmented by employing protein-protein interaction(PPI)network analysis and Cytoscape-based computational algorithms.The mRNA expression levels of the aforementioned pivotal genes were detected by real-time fluorescent quantitative reverse transcription PCR(RT-qPCR).Results A total of 947 RA-associated DEGs were identified from GEO dataset,and then 202 genes related to RA angiogenesis were further delineated.PPI network analysis and Cytoscape algorithm finally identified 3 key genes,that is,CXCL8,IL-1B,and STAT1.The results of RT-qPCR showed that the mRNA expression levels of MIP-2,GCP-2,IL-1B and STAT1 in RA lesions were significantly higher than those in normal controls(P<0.05).Conclusion With aid of bioinformatics analysis,our study has screened and validated key genes associated with angiogenesis in RA,namely CXCL8,IL-1B,and STAT1,which providing a theoretical basis for elucidating the potential mechanisms underlying RA-induced angiogenesis and developing targeted therapeutic strategies.

Forensic medicine has been designated as a first-level discipline,presenting new opportunities and challenges for the development of forensic medicine.Since the 1980s,the establishment of foren-sic medicine discipline and the cultivation of high-level forensic talents have become hot topics in the development of forensic medicine in China.Since the 13th Five-Year Plan,the forensic team of Shanxi Medical University has been aiming at the forefront,proposing the development goals of"Five First-class"and the discipline development path"Six Major Achievements".It has selected benchmark disci-plines,identified gaps in disciplinary development,unified thoughts,formulated completion timelines,concentrated superior resources,assigned tasks to individuals,and created an"Organized Fill-in-the-Blank Format"forensic medicine discipline construction model with the characteristics of the new era.The construction model of forensic medicine has achieved good results in the goals,discipline frame-work,scientific research,talent cultivation,discipline team and platform construction,forming a rela-tively complete discipline construction and management system,and accumulating valuable experience for the construction of first-level discipline and high-level talent cultivation of forensic medicine.

Objective:To analyze the reoperation rate and causes during the early adoption phase of unilateral biportal endoscopy (UBE).Methods:The clinical data of 180 patients who underwent UBE performed by a single surgeon at Beijing Friendship Hospital, Capital Medical University from October 2021 to June 2023 were retrospectively analyzed. Clinical and imaging data of patients who underwent reoperation were collected to analyze the causes of reoperation, and the clinical efficacy of the reoperations was also followed up. Measurement data were expressed as mean ± standard deviation ( ± s), and t-test was used before and after treatment. Results:A total of 180 patients who underwent UBE were included in this study, of which 6 patients underwent reoperation, and the reoperation rate was 3.33%. Among them, 3 cases occurred in the first 90 surgeries and the other 3 occurred in the subsequent 90 surgeries. The causes of reoperation were as follows: recurrent lumbar disc herniation at the same segment postoperatively in 2 cases, insufficient decompression in 2 cases, disc herniation following isolated decompression in 1 case, and immediate postoperative perianal numbness in 1 case. The time between the initial surgery and reoperation ranged from 0 to 187 days, with an average of 63.3 days. The average follow-up time after reoperation was 18.3 months. The visual analogue scale (VAS) and Oswestry disability index (ODI) scores of the patients at the last follow-up were significantly improved compared with those before operation (VAS score of low back pain: 5.2 ± 1.7 before operation, 1.2 ± 0.8 at the last follow-up, P<0.001; VAS score of leg pain: 7.2 ± 1.5 before operation, 1.2 ± 1.2 at the last follow-up, P<0.001; ODI score: 67.3 ± 5.7 before operation, 20.2 ± 8.2 at the last follow-up, P<0.001). The postoperative modified MacNab scores were generally satisfactory (4 cases were rated as excellent, accounting for 66.7%; 2 cases were rated as good, accounting for 33.3%). Except for one patient who experienced dural injury during open revision surgery, there were no serious complications such as nerve damage. Conclusions:In the early stages of UBE surgery, recurrent lumbar disc herniation and inadequate decompression are the primary reasons for reoperation, typically occurring within the first three months postoperatively. Reoperation does not significantly increase the risk of nerve injury. Enhanced early postoperative follow-up is recommended. For symptomatic patients, a second surgery with thorough decompression can yield satisfactory treatment outcomes.

Objective:To apply bioinformatics methods to screen and analyze differentially expressed genes and biological processes specific to peripheral blood mononuclear cells in postmenopausal women with osteoporosis.Methods:From the Gene Expression Omnibus database, GSE56814, GSE56815, and GSE2208 datasets were screened as the research objects. The limma package in R language was used to screen differentially expressed genes, and the multigene Meta-analysis function in Metascape platform was utilized to perform enrichment analysis of gene ontology and pathway. Protein-protein interaction network construction, module analysis, core gene, and enrichment analysis will be carried out.Results:In the GSE56814 dataset, there were 84 significantly up-regulated genes and 73 significantly down-regulated genes. In the GSE56815 dataset, there were 8 significantly up-regulated genes and 33 significantly down-regulated genes. In the GSE2208 dataset, there were 21 significantly up-regulated genes and 10 significantly down-regulated genes. The multigene Meta-analysis identified 3 modules and 19 core genes in the Metascape platform. The core genes of MCODE1 included STXBP2, EIF2S2, EIF3J, PTPN6, FLNA, HLA- DQA1, CTSD, HSPA6, HLA- DPB1, EIF3E, PLEC. They mainly enriched formation of cytoplasmic translation initiation complex, antigen processing and presentation of exogenous peptide antigen via major histocompatibility complex Ⅱ, cytoplasmic translational initiation, nsp1 from SARS-CoV-2 inhibits translation initiation in the host cell, programmed cell death 1 signaling pathway, allograft rejection reaction. The core genes of MCODE2 included FOS, FOSB, EGR1, EGR2, JUNB. They mainly enriched RNA polymerase Ⅱ-specific, DNA-binding transcription activator activity, cellular response to salt, nerve growth factor-stimulated transcriptional pathways, nuclear kinase and transcription factor activation activation pathways, neurotrophic receptor tyrosine kinase 1 signaling pathway. The core genes of MCODE3 included CEBPA, H2AC6, SPI1. They mainly enriched transcriptional regulation of granulopoiesis. Conclusion:This study obtained a total of 3 modules, 19 core genes, and enriched them in the biological processes related to postmenopausal osteoporosis, providing new ideas and biological targets for exploring its occurrence pathogenesis and drug treatment.

Objective:To establish a quality standard system for Descurainiae Semen under the requirements of German Pharmaceutical Codex (DPC); To compare the similarities and differences between DPC and the Pharmacopoeia of the People's Republic of China regarding the establishment of a quality standard system for TCM medicinal materials. Methods:Based on the requirements of DPC, and referring to the relevant methods of Pharmacopoeia of the People's Republic of China, the quality of 30 batches of Descurainiae Semen samples were assessed by observing the appearance and microscopic characteristics and determining their loss on drying, total ash content, and ash insoluble in hydrochloric acid. A TLC identification method was established based on a silica gel G TLC plate, using a developing agent composed of ethyl acetate, formic acid, and water in the ratio of 7:1.5:2.5 ( V/ V/ V). The method utilized rutin and quercetin as indicators for the System Suitability Test (SST), and took quercetin-3-O-β-D-glucose-7-O-β-D-gentiobioside and isorhamnetin 3-O-β-D-glucose-7-O-β-D-gentiobioside as the index. Based on the content determination method for Descurainiae Semen in the Pharmacopoeia of the People's Republic of China, a content determination method was established with quercetin-3-O-β-D-glucose-7-O-β- D-gentiobioside as the index. Results:The loss on drying for the 30 batches of samples ranged from 6.15% to 12.0%, with the total ash content ranged from 3.17% to 9.44%, and the ash insoluble in hydrochloric acid content ranged from 0.14% to 4.82%. The resolution of rutin and quercetin met the DPC's requirements for the SST criteria in TLC identification, and all batches of samples showed good separation of the index components. This method could effectively distinguish Descurainiae Semen from Lepidii Semen. Using modern chromatographic and spectroscopic techniques, the structure of the chromatographic peak adjacent to the component of the index (quercetin-3-O-β- D-glucoside-7-O-β-D-gentiobioside) was identified as descuraic anhydride B. The resolution between the two components in all batches of samples was greater than 3.1, which met the DPC's requirements for the SST criteria in content determination. The results of the methodological investigations met the requirements for content determination. The content of quercetin-3-O-β- D-glucose-7-O-β-D-gentiobioside in 30 batches of samples ranged from 0.062%-0.125%.Conclusion:The established quality standard system for Descurainiae Semen in this article is comprehensive, and meets the requirements of the DPC, which can be used for the quality control of Descurainiae Semen.

The accumulation of uremic toxins such as urea nitrogen, blood creatinine, and uric acid of patients with renal failure in vivo would lead to aggravated kidney damage. In this study, coated aldehyde oxy-starch (CAO) was used as an adsorbent to investigate its in vitro adsorption performance on renal failure indexes for urea, indoxyl sulfate (INS), monomethylamine (MMA), dimethylamine (DMA), uric acid (UA), and creatinine (Cr). The effects of variables such as pH, temperature, concentration, dosage, and time on the adsorption capacity of CAO were systematically investigated, employing analytical techniques of high-performance liquid chromatography (HPLC) and gas chromatography (GC). The results revealed that CAO exhibited a strong adsorption capacity for urea, INS, and MMA, alongside a moderate adsorption capacity for DMA, UA, and Cr. The adsorption kinetics and thermodynamic studies indicated that the adsorption of urea and UA by CAO were fitted in pseudo-first-order kinetics, and the adsorption isotherm aligned with the Freundlich adsorption model. The enthalpy change ΔH of urea in adsorption was in the range of 40 to 60 kJ·mol^-1, which demonstrated the presence of strong adsorption force due to the interactions of coordinating groups. The ΔH of UA was greater than 80 kJ·mol^-1, indicating the generation of chemical bonds during the adsorption. Both of them, Gibbs free energy ΔG was less than 0, within the range of -20 to 0 kJ·mol^-1, suggested that the adsorption of urea and UA by CAO occurred spontaneously as physical adsorption process. The adsorption entropy ΔS of urea and UA was > 0, which indicated an increase in entropy throughout the adsorption. The infrared spectroscopygram showed the formation of a chemical bond, specifically the imine bond, following the adsorption of urea by CAO, thereby indicating a chemical reaction during the adsorption. This study elucidates the adsorption mechanism of CAO on various indexes of renal failure, providing a scientific basis for its clinical usage.