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.

Mitochondrial biogenesis represents a promising therapeutic target in triple-negative breast cancer (TNBC) due to its essential role in cancer cell metabolism and survival. The natural compound γ-Elemene exhibits potent anti-tumor activity, but its effects on mitochondrial regulation in TNBC remain unclear. In this study, we demonstrate that γ-Elemene induces dose-dependent cytotoxicity in MDA-MB-468 and HCC1806 TNBC cells while significantly impairing mitochondrial function, as shown by reduced membrane potential, oxidative phosphorylation capacity, and ATP production. γ-Elemene treatment markedly suppressed mitochondrial biogenesis, decreasing mitochondrial DNA content and downregulating key mitochondrial genes and proteins. These effects were associated with reduced expression of the master regulators NRF1 and TFAM, but independent of PGC-1α expression levels.Mechanistically, γ-Elemene upregulated the acetyltransferase GCN5, leading to enhanced PGC-1α acetylation. This upregulation occurs primarily through increased GCN5 transcription. Genetic ablation of GCN5 completely reversed γ-Elemene-induced PGC-1α acetylation and restored mitochondrial biogenesis and cell viability, establishing a critical role for GCN5 in mediating these effects. Our findings reveal a novel mechanism whereby γ-Elemene disrupts mitochondrial function in TNBC through GCN5-mediated PGC-1α acetylation, providing new insights into its anti-cancer properties and potential therapeutic applications against TNBC.

Objective:This study aimed to examine the association between malnutrition diagnosed by the Global Leadership Initiative on Malnutrition(GLIM)criteria and clinical outcomes in surgical patients,as well as to assess its prognostic impact on postoperative adverse clinical outcomes.Methods:Electronic databases,including PubMed,Embase,Web of Science,CINAHL,Scopus,The Cochrane Library,Clinical Trials,CNKI,Wanfang Data Knowledge Service Platform,and the Chinese Biomedical Literature Database,were systematically searched.Relevant cohort studies utilizing GLIM criteria to preoperatively diagnose malnutrition in surgical inpatients were included.The exposed group comprised surgical patients diagnosed with preoperative malnutrition using GLIM criteria,while the control group consisted of surgically treated patients without malnutrition as per GLIM criteria.Literature quality was evaluated using the Newcastle-Ottawa Scale(NOS),and meta-analysis was performed using Review Manager 5.4 software.Results:Fourteen literatures were included,with a total sample size of 10,045 patients.Meta-analysis revealed that the malnourished group had a higher incidence of postoperative complications compared to the non-malnourished group[risk ratio(RR)=1.81,95%CI:1.66～1.98),P<0.00001].Additionally,the incidence of severe complications was significantly higher in GLIM-diagnosed malnourished patients.The malnourished group exhibited poorer overall survival[hazard ratio(HR)=1.90,95%CI:1.55～2.34,P<0.00001]and disease-free survival[HR=2.25,95%CI:1.02～4.93,P=0.04]compared to the non-malnourished group.Conclusion:GLIM-diagnosed malnutrition is significantly associated with adverse clinical outcomes in surgical patients,increasing postoperative complication rates and reducing overall and disease-free survival.The GLIM criteria demonstrate value in predicting adverse clinical outcomes in this population.Further high-quality studies are warranted to validate these findings.

With the rapid development of generative artificial intelligence(GAI)technologies,their widespread application in academic research and writing is continuously expanding the boundaries of sci-entific inquiry.However,this trend has also raised a series of ethical and regulatory challenges,inclu-ding issues related to authorship,content authenticity,citation accuracy,and accountability.In light of the growing involvement of AI in generating academic content,establishing an open,controllable,and trustworthy ethical governance framework has become a key task for safeguarding research integrity and maintaining trust within the academic community.This expert consensus outlines ethical requirements across key stages of AI-assisted academic writing-including topic selection,data management,citation practices,and authorship attribution.It aims to clarify the boundaries and ethical obligations surrounding AI use in academic writing,ensuring that technological tools enhance efficiency without compromising in-tegrity.The goal is to provide guidance and institutional support for building a responsible and sustainable research ecosystem.

T-cell acute lymphoblastic leukemia (T-ALL) is a highly aggressive hematologic malignancy with a poor prognosis, despite advancements in treatment. Many patients struggle with relapse or refractory disease. Investigating the role of the super-enhancer (SE) regulated gene ubiquitin-specific protease 20 (USP20) in T-ALL could enhance targeted therapies and improve clinical outcomes. Analysis of histone H3 lysine 27 acetylation (H3K27ac) chromatin immunoprecipitation sequencing (ChIP-seq) data from six T-ALL cell lines and seven pediatric samples identified USP20 as an SE-regulated driver gene. Utilizing the Cancer Cell Line Encyclopedia (CCLE) and BloodSpot databases, it was found that USP20 is specifically highly expressed in T-ALL. Knocking down USP20 with short hairpin RNA (shRNA) increased apoptosis and inhibited proliferation in T-ALL cells. In vivo studies showed that USP20 knockdown reduced tumor growth and improved survival. The USP20 inhibitor GSK2643943A demonstrated similar anti-tumor effects. Mass spectrometry, RNA-Seq, and immunoprecipitation revealed that USP20 interacted with hypoxia-inducible factor 1 subunit alpha (HIF1A) and stabilized it by deubiquitination. Cleavage under targets and tagmentation (CUT&Tag) results indicated that USP20 co-localized with HIF1A, jointly modulating target genes in T-ALL. This study identifies USP20 as a therapeutic target in T-ALL and suggests GSK2643943A as a potential treatment strategy.

With the establishment of bio-psycho-social medical model,both social and psychological factors play an important role in the occurrence,development and treatment of diseases.Hypertension is a common chronic multiple disease in China,and patients are often complicated with depression and other e-motional disorders.The interaction between hypertension and depression significantly increases the risk of poor prognosis.Current studies have shown a bidirectional promoting relationship between hypertension and depression,and they have some com-mon pathogenesis.However,the specific mechanism of their co-morbidity has not been fully elucidated.Renin-angiotensin sys-tem(RAS)plays an important role in the regulation of hyperten-sion and depression and other emotions.It is composed of two antagonistic pathways.The balance is maintained by angioten-sin-converting enzyme 2(ACE2).Therefore,this article reviews the relationship and mechanism of RAS in hypertension,depres-sion and comorbid states,in order to provide new treatment ide-as for hypertension and depression.

Objective To investigate the neurovascular coupling(NVC)status in the acute phase of patients with minor ischemic stroke(MIS)or transient ischemic attack(TIA)due to intracranial large artery moderate-to-severe stenosis or occlusion using multimodal MRI techniques and to explore its correlation with quality of life(QoL).Methods This prospective,consecutive study enrolled patients with MIS or TIA due to intracranial large artery moderate-to-severe stenosis or occlusion form the Department of Neurology,the First Affiliated Hospital of Xi'an Jiaotong University,between June 2022 and October 2023.Recruit healthy subjects with matched age,sex,and handedness form the community during the same period.Patients were divided into left-sided involvement and right-sided involvement groups based on the affected side of the responsible vessel,while the healthy subjects were set as the healthy control group.Post-hoc power analysis was performed using G*Power 3.1 software.General characteristics(age,gender,body mass index,education level)were collected and compared across all three groups.Clinical data and QoL assessment were collected and compared between the two patient groups.Collected clinical data including type of cerebrovascular events(TIA,MIS),the National Institutes of Health stroke scale(NIHSS)score at admission,the responsible vessel(internal carotid artery,middle cerebral artery)and its side location,the degree of responsibility artery stenosis(moderate-severe stenosis[50%-99%stenosis rate],occlusion[100%stenosis rate]),the intracranial collateral circulation status(American Society of Interventional and Therapeutic Neuroradiology/Society of Interventional Radiology[ASITN/SIR]collateral circulation grading),cerebrovascular risk factors(hypertension,diabetes,hyperlipidemia,smoking history),and the laboratory test indicators at admission(glycated hemoglobin,triglycerides,total cholesterol,high-density lipoprotein cholesterol,low-density lipoprotein cholesterol,blood uric acid,blood homocysteine).QoL was assessed using the stroke impact scale(SIS),covering eight functional domains and a patient-reported overall recovery item.Multimodal MR data were acquired for all subjects.Whole-brain cerebral blood flow(CBF)images were generated using statistics parameter mapping 12(SPM 12)software,while regional homogeneity(ReHo)images were generated using DPABI software.The voxel-wise ratio of CBF to ReHo(CBF/ReHo)was calculated as the regional NVC parameter.Differences in regional NVC characteristics were compared between patient groups and the healthy control group.Correlations between NVC parameters and SIS scores within patient groups were explored.Results(1)A total of 38 patients with MIS or TIA due to intracranial large artery moderate-to-severe stenosis or occlusion were included(26 males,12 females,aged 36-69 years,with mean age of[52±11]years),with 23 in the left-sided involvement group and 15 in the right-sided involvement group.Nineteen healthy subjects were included(10 males,9 females,aged 37-67 years,with mean age of[53±10]years).Post-hoc power analysis showed statistical power of 0.808 for comparing the left-sided involvement group with the healthy control group and 0.762 for comparing the right-sided involvement group with control group.(2)No statistically significant differences were found on gender,age,education level,or body mass index across the three groups(all P＞0.05).No statistically significant differences were observed on the type of cerebrovascular event,cerebrovascular risk factors,distribution of the responsible vessel,degree of stenosis in the responsible vessel,admission NIHSS score,or laboratory test results between the two patient groups(all P＞0.05).There were no statistically significant differences in the total SIS score and the scores of subscales between the two patient groups(all P＞0.05).(3)Compared with the healthy control group,the left-sided involvement group exhibited reduced CBF/ReHo values in the left superior and middle temporal gyri,supramarginal gyrus,middle and inferior frontal gyri,precentral gyrus,angular gyrus,postcentral gyrus,insula,and posterior cerebellar lobe(FDR-corrected,all P＜0.05).In the right-sided involvement group,reduced CBF/ReHo values were observed in the right supramarginal gyrus,right postcentral gyrus,inferior temporal gyrus,and insula(FDR-corrected,all P＜0.05).(4)Correlation analysis revealed that the SIS total score in the left-sided involvement group negatively correlated with CBF/ReHo values in the right inferior frontal gyrus(T=-5.91)and the right middle temporal gyrus(T=-6.65,FDR-corrected,both P＜0.05).The SIS subscale score for activities of daily living in the left-sided involvement group showed negative correlations with CBF/ReHo values in the right angular gyrus(T=-7.36),right medial superior frontal gyrus(T=-6.97),right orbitofrontal cortex(T=-8.99),and left thalamus(T=-7.51,FDR-corrected,all P＜0.05).No significant correlation was observed between the SIS total score and CBF/ReHo values in patients with right-sided involvement group.The SIS subscale for communication score in the right-sided involvement group correlated with CBF/ReHo in the left lingual gyrus(T=-12.15),left olfactory cortex(T=-7.68),and right anterior cingulate and paracingulate cortex(T=-9.46,FDR-corrected,all P＜0.05).Conclusions Patients with MIS or TIA due to intracranial large artery moderate-to-severe stenosis or occlusion show abnormal NVC in the acute phase,especially those with left hemisphere involvement,who exhibit more extensive impairments.QoL in left-sided involvement patients is strongly linked to NVC in the right orbitofrontal cortex and right middle temporal gyrus.These findings require further validation in larger-scale studies.

Objective:To investigate the co-occurrence patterns of psychosocial and behavioral problems among children and to identify associated influencing factors.Methods:A multicenter cross-sectional survey was conducted in 2023. A cluster random sample of 19 176 children aged 6-16 years was recruited from middle-income areas across 10 provincial capitals and municipalities in China. Psychological and behavioral problems, including anxiety, compulsive behavior, social withdrawal, depression, somatic complaints, social problems, schizoid, delinquent behaviors, hyperactivity, sexual issues, and aggression, were assessed using the Achenbach Child Behavior Checklist parent version. Co-occurrence was defined as ≥2 concurrent problems. Children were divided into 4 groups by gender and age: boys aged 6-11 years, girls aged 6-11 years, boys aged 12-16 years, and girls aged 12-16 years. Those children who had psychosocial and behavioral problems were further categorized into the single-problem group, and the co-occurrence group based on assessment results. High-frequency co-occurrence phenotypes of children′s psychosocial and behavioral problems were identified. Demographic factors, such as parental employment, education, as well as psychosocial factors like parent-child relationship, screen time and outdoor activity, were investigated. χ 2 test was used to analyze differences between groups. Multivariate Logistic regression modeling was conducted to identify potential factors. Results:Among 14 711 children (7 501 boys, 7 210 girls) who provided effective questionnaires, the detection rates of single problem in the boys aged 6-11 years, girls aged 6-11 years, boys aged 12-16 years, and girls aged 12-16 years groups were 4.9% (171/3 461), 6.2% (193/3 120), 3.9% (158/4 040), and 5.1% (208/4 090), respectively; the detection rates of co-occurrence were 7.6% (262/3 461), 7.7% (241/3 120), 4.9% (199/4 040), and 5.7% (234/4 090), respectively. The overall detection rates of co-occurrence was higher than that of single problem ( χ2=25.47, P<0.001). Among children with co-occurrence, there were varied manifestations: in the boys aged 6-11 years group, the detection rates of social withdrawal (69.8% (183/262)), schizoid-like behavior (68.3% (179/262)), and compulsive behavior (67.6% (177/262)) were relatively high; in the girls aged 6-11 years group, the detection rates of schizoid-compulsive behavior (69.3% (167/241)), delinquent behavior (65.6% (158/241)), and hyperactivity (58.9% (142/241)) were relatively high; in the boys aged 12-16 years group, the detection rates of hyperactivity (78.9% (157/199)), compulsive behavior (67.3% (134/199)), and immature behavior (57.3% (114/199)) were relatively high; in the girls aged 12-16 years group, the detection rates of schizoid-like behavior (89.7% (210/234)), immature behavior (59.0% (138/234)), and cruelty (57.7% (135/234)) were relatively high. Maternal bachelor′s degree or higher ( OR=0.78, 95% CI 0.61-0.99, P=0.038) served as co-occurrence protective factors, whereas having 1 or more siblings, increased parent-child conflict and decreased parent-child interaction time ( OR=1.24, 1.41, 1.36; 95% CI 1.02-1.52, 1.15-1.73, 1.02-1.82, all P<0.05) were co-occurrence risk factors. Conclusions:Children exhibit strong co-occurrence tendencies in psychosocial and behavioral problems. Compulsive and schizoid traits are the predominant co-occurring phenotypes for childhood and girls respectively. ?Familial environment plays a critical role, necessitating ?multidimensional clinical assessments and ?family-centered interventions.

Objective:The aim of this study is to investigate the main active substances of Qilin pills by high performance liq-uid chromatogre-electrostatic field orbitrap mass spectrometry(HPLC-Q-Orbitrap/MS),and explore the mechanism of its action in the treatment of asthenozoospermia by combining network pharmacology and molecular docking.Methods:(1)Qilin pills were quantita-tively and qualitatively analyzed by HPLC-Q-Orbitrap/MS.(2)The top 100 compounds in Qilin pills were screened by content analy-sis and SwissADME,and their targets were predicted.The asthenozoospermia targets were searched through the database.And a"pro-tein-protein interaction"(PPI)network was constructed.KEGG and GO analysis was performed using the DAVID database.And a"drug-target-pathway"network was constructed.(3)SailVina was used for molecular docking.Results:(1)A total of 1 275 known components were found and ranked in Qilin pills by HPLC-Q-Orbitrap/MS analysis.(2)The top 100 compounds in Qilin pills predicted a total of 1 053 targets and 184 potential therapeutic targets for asthenozoospermia.KEGG pathway analysis and GO analysis showed that the treatment of asthenozoospermia by Qilin pills may be related to the steroid hormone synthesis pathway,the response to steroid hormones,the chromosomal region of cells and the activity of steroid hydroxylase.The mechanism of Qilin pills in treating as-thenozoospermia may be related to regulating the synthesis,metabolism and reaction process of sex hormone in the body.(3)The mo-lecular docking results of its key targets(CYP19A1,ESR1,HSP90AA1,p53,HIF1α and BCL2)showed that the key active ingredi-ents M030,M039,M043,M050,M055 and M073 of Qilin pills had spontaneous binding.It had a binding energy of less than-5 kJ/mol.Conclusion:The material basis of Qilin pills has been explored by this study.And the mechanism of action of Qilin pills in the treatment of asthenozoospermia is highly bound to the expression and response process of steroid hormones,which provides a theoretical basis for the clinical application of Qilin pills.

Excessive fat accumulation,viral infections and sustained inflammatory responses caused by non-alcoholic and alcoholic factors can contribute to liver inflammation,fibrosis and carcinogenesis,promoting the development of chronic liver disease.Gaining an in-depth understanding of the etiologic factors and underlying mechanisms that lead to chronic liver disease can help identify potential therapeutic targets for targeted therapy.Lactate,as an important substance in hepatic metabolism,has been found to be involved in the process of chronic liver disease through various pathways,and this review will provide a useful reference for the prevention and treatment of chronic liver disease.