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.

Aim To study the therapeutic effect of al-licin on senna-induced diarrhea in mice and to explore the underlying mechanism.Methods Forty-eight C57BL/6J mice were randomly divided into six groups:control,model,loperamide positive control group(2 mg·kg-1),allicin low-dose group(6 mg·kg-1),allicin medium-dose group(12 mg·kg-1)and allicin high-dose group(18 mg·kg-1).Except for the con-trol group,the diarrhea model was induced in the other groups by intragastric administration of senna leaf ex-tract.After drug administration,several diarrhea indi-ces were measured:the rate of loose stools,diarrhea index,accumulated frequency of loose stools at differ-ent time points within 5 hours,and small intestine pro-pelling rate.Serum levels of TNF-α and IL-6 were de-tected by ELISA.Serum NO content was determined u-sing the Griess method.The activities of SOD and CAT,as well as MDA content in the ileum and colon,were measured.The pathological changes and the ex-pression of mRNA related to intestinal barrier proteins in the ileum and colon were evaluated using HE stai-ning and RT-qPCR.Results Allicin improved diar-rhea symptoms in mice induced by senna leaf.It re-duced the rate of loose stools,diarrhea index,cumula-tive number of loose stools in five hours,and the intes-tinal propulsion rate.Allicin also protected the intesti-nal mucosa,decreased serum TNF-α and IL-6 levels,and lowered MDA content in the intestines.It in-creased serum NO levels and enhanced SOD and CAT activities in the intestines.Additionally,allicin upreg-ulated the mRNA expression of AQP1,AQP4,and ZO-1 in intestinal tissues.Conclusions Allicin has a significant therapeutic effect on senna-induced diarrhea in mice.The underlying molecular mechanisms may involve anti-inflammatory and antioxidant effects,in-creased NO content,and upregulation of mRNA ex-pression of aquaporins and tight-junction proteins.

Objective To verify the applicability of a pig STR multiplex amplification system for detecting processed foods containing pork and their digestive samples,and to evaluate its potential in food safety and forensic biological evidence analysis.Methods DNA profiles were obtained using the pig STR amplification system from food samples with different levels of processing(raw pork,boiled pork,fried pork,and sausage)and from digestive samples(rat gastric contents).The influence of processing methods on DNA integrity was assessed.The uniformity of large-scale processed ham products,the consistency of DNA profiles from different parts of the same sample,and the DNA degradation patterns after rat digestion were examined.Results STR profiling of pig DNA was successful in all tested samples.Short fragments showed high amplification stability,while long fragment signals weakened with increasing processing complexity.In processed ham products,DNA profiles were consistent across all sampled parts,with fragment drift within±0.5 bp.Analysis of rat gastric contents showed slight DNA degradation within 2 hours;after 3 hours,long fragment signals weakened,and after 4 hours,some loci signals were lost.Conclusion The pig STR multiplex amplification system exhibits excellent performance in detecting processed pork products and their digestive samples.It can meet the requirements of food traceability and forensic biological evidence analysis for processed pork,providing new insights for the advancement of forensic testing techniques in this field.

This study was aimed at investigating the effects and mechanisms of Toxoplasma gondii type Ⅰ(RH strain)ROP16 protein on proliferation and the cell cycle in mouse alveolar macrophage MH-S cells.We constructed a Toxoplasma gondii type Ⅰ(RH)ROP16 overexpression lentivirus,transduced MH-S cells,and then screened cells with puromycin to obtain a cell line stably overexpressing ROP16Ⅰ.RT-qPCR and western blotting were used to verify expression effects,CCK-8 assays were used to detect cell proliferation activity,and flow cytometry was used to detect cell cycle changes.Western blotting and RT-qPCR were used to detect the expression levels of p53,p21,CDK6,Cyclin D1,STAT3,p-STAT3(Y705),and JAK1 proteins or genes,and immunofluorescence was used to detect the expression levels of ROP16Ⅰ and p-STAT3(Y705)and their subcellular co-localization in MH-S cells.ROP16Ⅰ protein and gene expression were detected in MH-S cells transduced with lentivirus for ROP16Ⅰ overexpression.CCK-8 assays revealed that ROP16Ⅰ promoted the proliferation of MH-S cells(P＜0.01)and enhanced cell viability.Flow cytometry revealed that ROP16Ⅰ overexpression decreased the G0/G1 phase and elevated the G2 and S phases of the cell cycle in MH-S cells(P＜0.01 or P＜0.05).Compared with the MH-S cell group and MH-S-empty vector group,the MH-S-ROP16 cell group showed lower expression of p53 and p21 proteins;higher expression of CDK6,Cyclin D1,p-STAT3(Y705),and JAK1 proteins;lower expression of p53 and p21 mRNAs;and higher expression of CDK6 and Cyclin D1 mRNAs(all P＜0.01).Immunofluorescence revealed that ROP16Ⅰ co-localized with p-STAT3(Y705)in the nucleus and surrounding cytoplasm.Therefore,Toxoplasma gondii type Ⅰ(RH)ROP16Ⅰ protein activates the JAK-STAT3 pathway;shortens the G0/G1 phase and lengthens the G2/S phase of the cell cycle;and promotes cell proliferation.These findings provide a theoretical basis for revealing the mechanism of immune evasion of Toxoplasma gondii,and lay a foundation for research on the prevention and treatment of Toxoplasma gondii pneumonia.

To formulate an expert consensus on the principles of preoperative hair removal and provide scientific guidance for standardized removal of hair before surgical procedures so as to reduce the incidence of surgical site infections.METHODS Led by the Hospital Management Institute of National Health Commission of the People's Republic of China,this consensus was reached with the joint efforts from the expects of relevant fields such as surgeries,interventional therapies,nursing,and infection prevention and control.The consensus facilitates the classification and evaluation of literatures by following the evidence grade formulated by Oxford Evidence-based Medicine Center and focuses on the association of preoperative hair removal with surgical site infection,it reaches the evidence grade of expert consensus and recommendation intensity by integrating with discussions on meetings and clinical experience of the expects from relevant fields.RESULTS A total of 6 items of consensus were reached by summarizing the latest evidence on the aspects including the indications for preoperative hair removal,tools,range,timing and places.CONCLUSION The consensus,to some extent,make supplements to and complete the exiting regulations and standards.It provides guidance for the medical institutions to carry out the preoperative hair removal.

Bovine rotavirus(BRV)is an important pathogen causing diarrhea in calves.To understand the genomic charac-teristics and genetic variations in bovine rotavirus,and to further enrich data on the biological characteristics of rotavirus,we aimed to amplify 11 gene segments of the isolated and cultured G6P[1]bovine rotavirus BLL strain,perform whole genome se-quencing,and analyze the molecular characteristics.MEGA7.0 and DNAMAN software were used for homology and typing a-nalysis,and the whole genome phylogenetic tree was constructed to analyze genetic evolution relationships.The complete geno-type of the BLL strain was G6-P[1]-I2-R2-C2-M2-A3-N2-T6-E2-H3.Phylogenetic analysis of the VP7 and VP4 genes of the BLL strain showed that the VP7 gene had the highest homology with RVA/Cow-wt/HB01/China/2021,and the VP4 gene of the BLL strain was in the same branch as RVA/Human-tc/ISR/Ro8059/1995.From the sequence alignment of VP8*amino acids,the sialic acid domain of the BLL strain was found to be similar to that in other P[1]strains,but different from those in other types of strains,except for residue 189,which was the same as that in Ro8059 but different from that in other strains.The results suggested that the BLL strain might potentially infect humans.Therefore,continued monitoring and study of the biological characteristics of this strain are necessary to provide more information and evidence supporting further research on the cross-species transmission of group A rotavirus in China.

Objective:To assess the safety,efficacy and potential impact of stem cell therapy(SCT)in improving erectile dys-function(ED).Methods:A comprehensive search strategy was used to search the literatures on safety and efficacy evaluation of stem cell(SC)in the treatment of ED by human clinical trials from PubMed,Embase and Web of science databases with a search time frame from database creation to July 4,2024.The exclusion criteria were as follows:reviews,conference abstracts,animal experi-ments,and duplicate sample literature.Results:The study initially screened 1 773 papers,and 17 were included in the final analy-sis.These studies involved a total of 269 ED patients,and a variety of sources of stem cells had been used in the treatment of ED,in-cluding adipose-derived stem cells,bone marrow-derived stem cells,placental stroma-derived stem cells,umbilical cord-derived stem cells,dental pulp-derived stem cells,and oral mucosa-derived stem cells.All studies were conducted by injecting stem cells into the cavernous body of the penis,but there is no fixed standard for the amount of injection,injection site and number of injections.The op-timal treatment mode was still being explored.Patients' International Index of Erectile Function(IIEF)scores and Erection Hardness Score(EHS),peak systolic velocity(PSV),and end diastolic velocity(EDV)improved after treatment.But some studies showed that the efficacy of the treatment diminished with increasing time.No serious adverse effects were reported in any of the studies and none of the adverse effects persisted for a long period of time.The most common adverse effects included injection site reactions,and SCT showed a good safety and tolerability profile.Conclusion:SCT has the potential to be a promising and innovative regenerative therapy option for ED patients.In the future,with the advancement of stem cell technology,larger randomized controlled studies should continue to be conducted to explore standardized treatments,so as to further evaluate the long-term efficacy and safety of SCT for ED.

Objective:To investigate the positive rate,mutation type and distribution characteristics of thalassemia gene detection in children in Nanchong area.Methods:The common α and β-thalassemia gene mutation sites were detected in 1 254 children suspected of thalassemia by hematological screening in our hospital from January 2017 to December 2023,and the genotypes,detection rates and clinical characteristics of thalassemia in local children were statistically analyzed.Results:Among 1 254 children with suspected thalassemia,490 carriers were screened out,with a positive detection rate of 39.07％.Among them,220 cases(17.54％)were α-thalassemia,251 cases(20.02％)wereβ-thalassemia,and 19 cases(1.52％)were αβ compound thalassemia.Among 220 cases of α-thalassemia,the main genotypes were--SEA/αα,-α3.7/αα,-α3.7/--SEA and-α4.2/αα,accounting for 63.64％,18.64％,5.91％,and 5.00％,respectively.Among 251 cases of β-thalassemia,CD17,CD41-42,and IVS-Ⅱ-654 genotypes were the most common,accounting for 40.24％,29.88％,and 17.93％,respectively.In 19 cases of αβ compound thalassemia,the most common genotypes were-α3.7/αα compound CD41-42,--SEA/αα compound CD41-42,--SEA/αα compound CD17,accounting for 26.32％,15.79％,and 15.79％,respectively.In addition,compared with healthy individuals,red blood cell(RBC)in the thalassemia gene carriers was significantly increased,while hemoglobin(Hb),mean corpuscular volume(MCV),mean corpuscular hemoglobin(MCH),mean corpuscular hemoglobin concentration(MCHC)and red blood cell distribution width-standard deviation(RDW-SD)were significantly decreased(all P＜0.01).The ROC curve analysis showed that the area under the curve(AUC)of RDW-SD,MCHC,MCH,MCV,Hb and RBC were 0.827,0.707,0.823,0.863,0.603 and 0.882,respectively.The thalassemia gene carrying rates from 2017 to 2023 in Nanchong were 35.6％(54/154),28.43％(56/197),34.74％(74/213),40.56％(58/143),42.69％(73/171),45.86％(83/181),and 47.18％(92/195),respectively,showing an upward trend year by year.Conclusion:The positive detection rate of children's thalassemia gene in Nanchong is relatively high,and the genetic types are complex,with β-thalassemia as the main type.The genetic pattern shows obvious regional distribution characteristics.The genotypes of thalassemia in children are mainly--SEA/αα,-α3.7/αα,CD17,CD41-42 and IVS-Ⅱ-654,which are consistent with the genotypes of adults in this area,but different from high-risk areas such as Dongguan and Guangxi.

Objectives:To investigate the relationship between locations of ventricular septal perforation and 30-day prognosis in patients with acute myocardial infarction complicated by ventricular septal perforation.Methods:Clinical data of 150 acute myocardial infarction patients with ventricular septal perforation admitted to Fuwai Hospital of Chinese Academy of Medical Sciences and People's Hospital of Xinjiang Uygur Autonomous Region from January 2009 to October 2023 were retrospectively analyzed.Kaplan-Meier method was used to compare the difference in 30-day survival rate among patients with different sites of ventricular septal perforation.The impact of locations of ventricular septal perforation on 30-day prognosis of acute myocardial infarction patients was evaluated by multivariate Cox regression analysis(forward stepwise).Results:In acute myocardial infarction patients,the occurrence of anterior ventricular septal perforation was higher than that of posterior ventricular septal perforation(79.5%vs.20.5%,P<0.001).In the anterior ventricular septal perforation patients,females were more common(50.0%vs.22.6%,P=0.006),the blood glucose level was higher([10.51±5.99]mmol/L vs.[8.02±2.81]mmol/L,P=0.026),the left ventricular end-diastolic diameter was smaller([50.7±6.1]mm vs.[55.1±5.0]mm,P<0.001),the ventricular septal aperture was also smaller([9.8±4.6]mm vs.[12.6±5.4]mm,P=0.004),30-day mortality was higher(55.8%vs.35.5%,P=0.043)compared with posterior ventricular septal perforation patients.Multivariate Cox regression analysis(forward stepwise)showed that no transthoracic surgery or transcatheter closure(HR=26.344,95%CI:8.261-84.009,P<0.001)and anterior ventricular septal perforation(HR=2.432,95%CI:1.281-4.619,P=0.007)were associated with increased risk of 30-day all-cause mortality in patients with acute myocardial infarction complicated by ventricular septal perforation.Conclusions:In patients with acute myocardial infarction complicated by ventricular septal perforation,the incidence of anterior ventricular septal perforation is higher than posterior ventricular septal perforation and the 30-day all-cause mortality of anterior ventricular septal perforation patients is also higher.No transthoracic surgery or transcatheter closure and anterior ventricular septal perforation are the independent influential factors of 30-day all-cause mortality in patients with acute myocardial infarction and ventricular septal perforation.