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 explore the network structure of anxiety and depressive symptoms, and psychotic like experiences in junior and senior high school students with different sleep qualities, and to provide a reference for improving sleep quality in the population. Methods: A cross sectional online survey was conducted among 22 997 junior and senior high school students from seven junior and senior high schools in Luzhou City, Sichuan Province, using convenience sampling. The Pittsburgh Sleep Quality Index (PSQI), Generalized Anxiety Disorder-7 (GAD-7), Patient Health Questionnaire-9 (PHQ-9), and the 16item Prodromal Questionnaire (PQ-16) were administered. Independent sample t-test was used to compare mental health status between adolescents with and without sleep problems. Network analysis was applied to examine the symptom association patterns across gender and school stage subgroups. Results: The prevalence of sleep problems among junior and senior high school students was 22.58%. The total anxiety symptom score (8.92± 4.02 ), total depressive symptom score (13.35±5.66), and scores for each factor of PQ-16 (perceptual and sensory abnormalities, thinking abnormalities, negative symptoms, and specific perceptual and sensory abnormalities) (3.32±3.32, 2.08±2.36, 3.36± 2.74 , 1.44±1.86) in the group with sleep problems were all significantly higher than those in the group without sleep problems ( 3.43 ±3.33, 5.03±4.73; 0.63±1.52, 0.47±1.11, 0.77±1.48, 0.25±0.79), with statistically significant differences ( t =99.60, 106.54, 82.49, 68.51, 89.09, 67.30, all P <0.01). In females with sleep problems, the anxiety-depressive symptoms edge weight was the highest (0.44). In males with sleep problems, the "sleep latency-sleep efficiency" edge weight was the highest (0.43), and the strength centrality values of "perceptual abnormalities" "medication factor" and "sleep latency" ranked the higher (1.32, 1.31 and 1.25). The network connectivity strength of the sleep problem group was higher in senior high school students than in junior high school students, and the strength centrality (1.12) and betweenness centrality (0.12) of negative symptoms were higher than those in junior high school students (1.02 and 0.11). Conclusions The network associations between sleep problems and psychological symptoms in junior and senior high school students exhibit gender and school stage specific characteristics. Differentiated intervention strategies should be tailored to specific subgroups.

In modern society, sugary foods have become an integral part of many people′s lives. However, excessive sugar consumption has adverse effects on both overall health and oral health, serving as a contributing factor to the global increasing incidence in oral diseases, cardiovascular diseases, cancers, obesity, and diabetes. In response to the health risks related to high-sugar diets, the World Health Organization (WHO) and World Dental Federation (FDI) have proposed initiatives and recommendations, with various governments implementing different policies and strategies to reduce sugar intake. Chinese government has also taken proactive measures. The "Healthy China Action (2019-2030)" initiative introduced by the State Council in 2019 established a crucial benchmark in limiting the average daily intake of added sugar to 25 g per person forward to 2030. Experts from Chinese Center for Disease Control and Prevention and the field of oral health have meticulously examined the impacts of sugar reduction on oral health, as well as strategies, methods, and practical considerations related to reducing sugar intake through several meeting and wrote the "Expert consensus: reducing free-sugar for caries prevention", which was subsequently reviewed and revised based on the feedback from multiple stakeholders. They have conducted thorough analyses of global trends in sugar reduction and best practices to provide valuable insights to China for crafting effective policies and strategies on sugar reduction. This consensus mainly includes the classification of free sugars, the latest scientific evidence on dental caries, recommendations from WHO on sugar-sweetened beverage taxes, nutrition labeling, advertising, food reform, adjusting supply systems, education, and promotion strategies, as well as sugar reduction actions taken by various governments around the world. Combining the actual situation in China, policy recommendations and authoritative popular science knowledge on sugar reduction for caries prevention to public are proposed to advocate for experts in multiple fields to focus on sugar reduction for caries prevention, promote the work process, and provide the scientific basis for oral health educators.

Objective: To predict and screen potential biomarkers of systemic lupus eythematosus(SLE) based on machine learning algorithms and structural biology, and to reveal their mechanisms of action and to provide new targets for disease diagnosis and treatment. Methods: Four machine learning algorithms, random forest(RF), eXtreme gradient boosting(XGBoost), support vector machine(SVM), least absolute shrinkage and selection operator(LASSO), were used to analyze the gene expression data of SLE patients in GEO(datasets: GSE121239 and GSE11907) to analyze the gene expression data of SLE patients and screen key markers. Peripheral blood single nucleated cells(PBMCs) from SLE patients were collected and RT-qPCR was used to detect differential gene expression levels. Subsequently, GSEA enrichment analysis was used to identify biomarker-related pathways. CIBERSORT immune infiltration analysis and protein interactions network were applied to calculate the sample immune cell infiltration abundance. Single-cell data were analyzed for gene expression specificity in immune cells. Interaction relationships in combination with AlphaFold3(AF3) were predicted. Results: Multiple algorithms were screened together to identify the unique marker gene HERC5 , and expression analysis of multiple datasets showed that HERC5 was highly expressed in SLE compared to the normal group (P < 0. 05) , and RT⁃qPCR verified the same trend (P = 0. 006 2) . Functional enrichment analysis identified the major pathway promoted by HERC5 in SLE as the interferon receptor signalling pathway (P < 0. 05) . Immune infiltration analysis showed that HERC5 was closely associated with immune cells (Neutrophils : r = 0. 39 , P < 0. 05 ; Memory B cells : r = 0. 33 , P < 0. 05 ; Activated dendritic cell : r = 0. 52 , P < 0. 05) . Most HERC5 ⁃related interacting proteins were associated with SLE ,and potential transcription factors of HERC5 and its related genes were also significantly associated with immune responses. Conclusion The HERC5 gene is an important biomarker for SLE , which upregulates the interferon pathway to promote SLE progression and provides a new target for SLE diagnosis and treatment.

Objective To analyze the current status of occupational health literacy (OHL) among front-line workers in the metal products industry and to explore its influencing factors. Methods A total of 5 193 front-line workers from the metal products industry in 14 prefecture-level cities in Guangdong Province were selected as the research subjects by the stratified cluster random sampling method. The Occupational Health Literacy Questionnaire of National Key Populations was used to assess their OHL levels. To analyze the influencing factors of OHL, binary logistic regression analysis was conducted. Results The overall OHL level among the participants was 40.0% (2 079/5 193). The result of binary logistic regression analysis showed that workers with lower educational level, lower average monthly personal income, and smaller enterprise size had lower OHL levels (all P<0.01). In addition, workers in foreign-funded enterprises had higher OHL levels than those in private enterprises (P<0.01). Conclusion There remains considerable room for improvement in OHL among front-line workers in the metal products industry. Priority focus is to improve OHL among workers with lower education and income levels, as well as those employed in private and micro- or small-sized enterprises.

Glutamine provides carbon and nitrogen to support the proliferation of cancer cells. However, the precise reason why cancer cells are particularly dependent on glutamine remains unclear. In this study, we report that glutamine modulates the tumor suppressor F-box and WD repeat domain-containing 7 (FBW7) to promote cancer cell proliferation and survival. Specifically, lysine 604 (K604) in the sixth of the 7 substrate-recruiting WD repeats of FBW7 undergoes glutaminylation (Gln-K604) by glutaminyl tRNA synthetase. Gln-K604 inhibits SCFFBW7-mediated degradation of c-Myc and Mcl-1, enhances glutamine utilization, and stimulates nucleotide and DNA biosynthesis through the activation of c-Myc. Additionally, Gln-K604 promotes resistance to apoptosis by activating Mcl-1. In contrast, SIRT1 deglutaminylates Gln-K604, thereby reversing its effects. Cancer cells lacking Gln-K604 exhibit overexpression of c-Myc and Mcl-1 and display resistance to chemotherapy-induced apoptosis. Silencing both c-MYC and MCL-1 in these cells sensitizes them to chemotherapy. These findings indicate that the glutamine-mediated signal via Gln-K604 is a key driver of cancer progression and suggest potential strategies for targeted cancer therapies based on varying Gln-K604 status.
Glutamine/metabolism* ; Myeloid Cell Leukemia Sequence 1 Protein/genetics* ; Humans ; Proto-Oncogene Proteins c-myc/genetics* ; Cell Proliferation ; Signal Transduction ; Neoplasms/pathology* ; F-Box-WD Repeat-Containing Protein 7/genetics* ; Cell Survival ; Cell Line, Tumor ; Apoptosis

Objective To observe the clinical efficacy of thumb-tack needling therapy combined with Oxycodone Hydrochloride Sustained-Release Tablets in treating patients with severe cancer pain caused by malignant tumors.Methods A total of 60 patients diagnosed with severe cancer pain who were admitted to the Traditional Chinese Medicine Department of Qingpu Branch,Zhongshan Hospital Affiliated to Fudan University between November 2023 and December 2024 were selected as study subjects.Patients were randomly divided into an observation group and a control group using a random number table,with 30 cases in each group.The control group received conventional western medicine pain management,while the observation group received additional thumb-tack needling therapy based on the control group's treatment.The treatment duration was 2 weeks.After treatment,clinical efficacy was evaluated by observing changes in European Quality of Life-5 Dimensions(EQ-5D)scores,Numerical Rating Scale(NRS)scores,Cancer Pain Self-Efficacy Scale(CPSS)scores,and European Organization for Research and Treatment of Cancer Quality of Life Questionnaire(EORTC QLQ-C30)scores in both groups before and after treatment.Changes in serum levels of prostaglandin E2,endothelin-1,β-endorphin,and substance P were also compared.Safety and adverse reactions were assessed.Results(1)The total analgesic effective rate was 76.67％(23/30)in the observation group and 46.67％(14/30)in the control group.The total effective rate in the observation group was significantly higher than that in the control group,with a statistically significant difference(P＜0.05).(2)After treatment,serum levels of prostaglandin E2,endothelin-1,β-endorphin,and substance P were significantly improved in both groups(P＜0.05),and the improvement in the observation group was significantly greater than that in the control group,with a statistically significant difference(P＜0.05).(3)After treatment,EQ-5D scores,NRS scores,and CPSS scores were significantly improved in both groups(P＜0.05),and the improvement in the observation group was significantly greater than that in the control group,with a statistically significant difference(P＜0.05).(4)After treatment,EORTC QLQ-C30 scores were significantly improved in both groups(P＜0.05),and the improvement in the observation group was significantly greater than that in the control group,with a statistically significant difference(P＜0.05).(5)The incidence of adverse reactions was 53.33％(16/30)in the observation group and 83.33％(25/30)in the control group.The incidence of adverse reactions in the observation group was significantly lower than that in the control group,with a statistically significant difference(P＜0.05).Conclusion Thumb-tack needling therapy combined with Oxycodone Hydrochloride Sustained-Release Tablets significantly alleviates pain symptoms,improves health status and self-efficacy,and enhances the quality of life in patients with severe cancer pain caused by malignant tumors.

Objective:To construct a clinical decision-making ability indicator system based on evidence-based practice for pediatric nursing interns, and to provide a scientific basis for clinical teaching and evaluation.Methods:A method combining literature analysis, Delphi expert consultation, and empirical research was used. Firstly, a systematic search of Chinese and English databases (2018-2023) was conducted. Literature was screened based on the PICO framework and evidence-based data were extracted, resulting in a preliminary system consisting of 4 primary indicators, 12 secondary indicators, and 39 tertiary indicators. Subsequently, the indicators were revised through two rounds of Delphi expert consultation (25 experts with 19-27 years of work experience). The expert authority coefficients (Cr) were 0.898-0.907 and the Kendall's concordance coefficients were 0.351-0.420 ( P<0.001). Finally, the analytic hierarchy process was used to determine the weights, and the reliability and validity were verified through a questionnaire survey (sample size: 30 participants in preliminary survey and 58 participants in formal survey). Results:The constructed indicator system included 4 primary indicators (weights), 13 secondary indicators, and 42 tertiary indicators. The weights of the primary indicators were as follows: knowledge integration ability (0.300), evidence-based practice ability (0.250), clinical judgment ability (0.280), and ethical decision-making ability (0.170). The importance scores of all items exceeded 4.0 points (out of 5 points), and the coefficients of variation were less than 0.20. The reliability and validity tests showed that the Cronbach's α of the overall scale was 0.89, and the intraclass correlation coefficient was 0.88. The cumulative variance contribution rate of exploratory factor analysis was 69.30%. The confirmatory factor analysis demonstrated a good model fit with a comparative fit index of 0.93 and a root mean square error of approximation of 0.05. Conclusions:This indicator system has high scientificity and practicality, and can provide a reference for the standardized cultivation and evaluation of clinical decision-making ability of pediatric nursing interns. In the future, it is necessary to strengthen advanced evidence-based skills training and long-term application effectiveness tracking.

AIM:To explore the therapeutic effect of Tongfeng-Qingli mixture(TFQLM)and its mechanism in hyperuricemic(HUA)rats based on uric acid(UA)transporter and Janus kinase 2(JAK2)/signal transducer and acti-vator of transcription 3(STAT3)signaling pathway.METHODS:(1)In vivo experiment:36 male SD rats were random-ly divided into control(CON)group,model(MOD)group,benzbromarone(BEN)group,low-dose TFQLM(TFQLM-L)group,medium-dose TFQLM(TFQLM-M)group,and high-dose TFQLM(TFQLM-H)group,with 6 rats in each group.In all groups except CON group,HUA was induced in rats by giving hypoxanthine(HP)combined with potassium oxybate(OP)for 35 consecutive days.The rats in CON group were given sodium carboxymethyl cellulose solution by gavage.A fully automatic biochemistry analyzer was used to detecte serum UA,serum creatinine(SCr)and blood urea nitrogen(BUN)levels.The xanthine oxidase(XOD)and adenosine deaminase(ADA)levels in the liver were detected by ELISA kits.The histopathological changes of kidneys were observed by HE staining.Immunohistochemistry was performed to de-tect urate transporter 1(URAT1)and glucose transporter 9(GLUT9),organic anion transporter 1(OAT1)and OAT3 ex-pression in the kidney.Western blot was used to measure the protein levels of URAT1,GLUT9,OAT1,OAT3,interleu-kin-6(IL-6),tumor necrosis factor-α(TNF-α),JAK2,p-JAK2,STAT3,p-STAT3 and repressor of cytokine signaling 3(SOCS3)in the kidney.(2)In vitro experiments:HUA cellular model was established by UA stimulation in HK2 cells,and the protein levels of URAT1,GLUT9,OAT1,OAT3,IL-6,TNF-α,JAK2,p-JAK2,STAT3,p-STAT3,and SOCS3 were detected by Western blot.RESULTS:Compared with MOD group,serum UA,SCr and BUN levels of the rats in all TFQLM groups were reduced(P<0.05).The XOD and ADA levels in liver tissues were significantly reduced(P<0.05).The protein levels of URAT1,GLUT9,IL-6,TNF-α,JAK2,p-JAK2,STAT3,p-STAT3 and SOCS3 were decreased(P<0.05),and OAT1 and OAT3 protein expression was increased(P<0.05)in kidneys and HK2 cells.CONCLUSION:By establishing rat and HK2 cell HUA models,it is hypothesized that TFQLM may reduce UA levels and attenuate renal inflammation in HUA rats,and its mechanism may be related to the regulation of UA transport proteins and inhibition of the JAK2/STAT3 signaling pathway.