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.

Purpose: We aimed to compare broad-spectrum antibiotic use between hospice and nonhospice patients with cancer at the end of life using nationwide data from Korea. Methods: In this retrospective cohort study, we analyzed the Korean National Health Insurance Service data of adult patients with cancer who died between 2018 and 2021. Hospice users were defined as patients who received inpatient, home-based, or consultation-based hospice care before death. We applied propensity score matching (1:2) to balance the baseline characteristics of the hospice and non-hospice groups. Broad-spectrum antibiotic use, including anti-pseudomonal penicillins, anti-pseudomonal cephalosporins, carbapenems, and glycopeptides, was assessed during the last 3 months of life using prescription proportions and days of therapy per 1,000 patient-days. Results: After matching, 38,102 hospice and 75,736 non-hospice users were analyzed. During the last 3 months of life, 74.6% of hospiceand 79.0% of non-hospice users received at least one broad-spectrum antibiotic (P＜0.001).The proportion of patients receiving broad-spectrum antibiotics was generally lower amonghospice users across all time intervals (P＜0.001), and the number of days of therapy wasalso lower, with the largest differences observed during the final week and last 3 days of life.Subgroup analyses showed the highest antibiotic exposure among patients with hematologic and pancreatobiliary cancers, particularly in the non-hospice group. Conclusion Hospice involvement was associated with lower use and reduced exposure to broad-spectrum antibiotics among patients with cancer near the end of life. These findings support the alignment of end-of-life treatment decisions with the comfort-oriented goals of hospice care.

Purpose: This study aimed to explore the practices, perceptions, and barriers related to specialty palliative care (SPC) referrals among oncologists in Korea, highlighting the clinical implications of early integration. Materials and Methods: A cross-sectional online survey targeting board-certified hemato-oncology specialists was conducted between August 1-25, 2024. The survey assessed referral practices, attitudes toward early SPC integration, referral criteria, barriers, and institutional characteristics. Results: A total of 227 oncologists participated (response rate, 36.7%). Among them, 68.7% reported frequent SPC referrals, with higher referral rates observed among younger physicians, those in tertiary hospitals, and institutions with in-house SPC teams (p < 0.001). Although 74.9% supported early SPC integration, referrals were often inconsistently timed, frequently occurring after disease progression or at the discontinuation of chemotherapy. For time-based referrals, the most commonly endorsed triggers were disease progression despite palliative second-line treatment and a prognosis of expected mortality within 6-12 months. Need-based referral triggers such as patient or family requests (96.5%), psychological distress (89.9%), or uncontrolled symptoms (83.3%), were also widely endorsed. The major barriers to early SPC integration included patient and family resistance (70.0%) and limited availability of SPC teams (34.4%). Conclusion This study emphasizes the importance of systematic efforts to promote timely SPC integration in Korea, including education to raise patient awareness, improved referral systems, and enhanced infrastructure. The positive attitudes toward early SPC among oncologists reflect a growing recognition of its value, highlighting the need for strategies that align with international standards.

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.

ObjectiveMigraine is a leading neurological disorder and the fourth most common cause of years lived with disability worldwide, affecting nearly 116 million individuals. Although pharmacological treatments are available, their efficacy is often limited by side effects and variable response rates. Repetitive transcranial magnetic stimulation (rTMS) over the dorsolateral prefrontal cortex (DLPFC) offers a safe, non-invasive alternative for migraine management. However, the neurophysiological mechanisms, particularly how rTMS modulates local cortical excitability and distributed pain-related circuits, remain poorly understood. Elucidating these mechanisms is essential for optimizing treatment protocols and improving clinical outcomes. MethodsThis study employed concurrent transcranial magnetic stimulation and electroencephalography (TMS-EEG) to investigate neuroplastic and neurocircuitry mechanisms of DLPFC-rTMS in migraine. Study 1 compared 30 migraineurs and 28 healthy controls to identify abnormalities in TMS-evoked potentials (TEPs) and significant current density (SCD) within sensory-discriminative regions including the primary somatosensory cortex (S1) and posterior insula (pINS), cognitive-affective regions including the anterior insula (aINS) and midcingulate cortex (MCC), and a descending modulatory region, the periaqueductal gray (PAG). Study 2 used a single-blind, crossover, sham-controlled design in 34 healthy participants. Each participant received both active (10 Hz, 80% RMT, 1 500 pulses) and sham DLPFC-rTMS in counterbalanced order. TMS-EEG and cold pain tolerance were assessed before and after each session. ResultsIn Study 1, migraineurs showed a significantly less negative N120 amplitude compared to healthy controls (P=0.027, Cohen’s d=0.60), indicating local intracortical disinhibition. No group differences were observed for N40, P60, or P180 components. At the source level, migraineurs exhibited significantly higher SCD in the S1, pINS, aINS, and MCC (allQ<0.05), but not in the ventroposterior thalamus (vpTHAL), mediodorsal thalamus (mdTHAL), or PAG. In Study 2, active rTMS significantly reduced SCD from pre- to post-stimulation in the S1, aINS, and MCC (all Q<0.05). Sham stimulation also reduced SCD in the S1 (Q<0.05) but not in the aINS or MCC. Although no significant group-level analgesic effect was observed between active and sham conditions (P=0.107), correlation analyses revealed that greater SCD reductions in the S1 and MCC were significantly associated with higher post-rTMS pain tolerance (R=-0.487 and -0.495, both Q<0.01) and larger improvements in pain tolerance(R=-0.487 and -0.451, both Q<0.05). No such correlations were found following sham stimulation, suggesting that the behavioural relevance of neural changes is specific to active rTMS. ConclusionThis study provides novel evidence that migraineurs exhibit both local neuroplastic abnormalities (reduced N120 amplitude) and hyperactivity in key pain-processing regions (S1, pINS, aINS, MCC). A single session of DLPFC-rTMS reduced hyperactivity in the aINS, MCC, and S1. Notably, greater reductions in the S1 and MCC were associated with improved pain tolerance. These findings identify distinct cortical circuitries, particularly within the cognitive-affective pain network, that may serve as potential biomarkers for optimizing rTMS treatment in migraine and other chronic pain conditions. Future studies should validate these results in patient populations experiencing spontaneous migraine attacks and explore multi-session or accelerated rTMS protocols.

Objective To investigate the population composition,seasonal dynamics,and infestation levels of cockroaches in Lanzhou,China,and to provide information for the scientific development of cockroach control strategies.Methods Monitoring was conducted at three locations using the sticky trap method.Habitats included farm product markets,catering establishments,hotels,hospitals,and residential areas.Results From 2016 to 2023,the average cockroach density was 0.77 insects per board,with an average infestation rate of 10.84%.Blattella germanica was the dominant species.Seasonal density of cockroaches showed an approximately unimodal distribution,peaking in September.The highest average density and infestation rates were observed in farm product markets.Conclusions Cockroach density and infestation levels in Lanzhou remained relatively low.A comprehensive prevention and control strategy focusing on environmental management in key areas should be implemented according to the seasonal fluctuations.

Objective:To report the surveillance results of the distribution and antimicrobial resistance profile of clinical isolates in Anhui province.Methods:Surveillance data from 94 members of the Anhui Antimicrobial Resistance Surveillance Network（HuiNet）from October 2023 to September 2024 were collected，the major drug-resistant bacteria and the resistance to commonly used antibiotics were analyzed. WHONET 5.6 and SPSS 25.0 software were used for data analysis.Results:Among 240 339 clinical strains，Gram-negative bacteria accounted for 75.0%（180 153 strains）. The detected bacteria mainly include Escherichia coli（ n=53 587，22.3%）， Klebsiella pneumoniae（ n=39 774，16.5%）， Pseudomonas aeruginosa（ n=25 505，10.6%）， Staphylococus aureus（ n=19 438，8.1%）， Acinetobacter baumannii complex（ n=14 239，5.9%），and so on. The prevalence of methicillin-resistant Staphylococcus aureus（MRSA）and methicillin-resistant coagulase-negative Staphylococcus aureus（MRCNS）were 37.7%（7 112/18 853）and 73.9%（13 221/17 895），respectively. No vancomycin- and teicolanin-resistant Staphylococcus were detected. The prevalence of carbapenem-resistant Escherichia coli（CREC）and Klebsiella pneumoniae（CRKP）were 1.9%（971/51 991）and 12.3%（4 864/39 414），respectively. The resistance rate of CRKP to tigecycline and polycolistin B was 7.7% and 7.9%，respectively. The prevalence of carbapenem-resistant Acinetobacter baumannii（CRAB）complex and Pseudomonas aeruginosa（CRPA）were 57.9%（8 222/14 198）and 18.2%（4 569/25 052），respectively，with low resistance to polycolistin B（2.0% and 7.2%，respectively）. The detection rates of MRSA，MRCNS，CRAB complex，third-generation cephalosporin-resistant Escherichia coli（3GC-R-EC）and quinolone-resistant Escherichia coli（QREC）in northern Anhui were the highest（46.8%，77.1%，65.6%，57.6% and 55.5%，respectively），which were higher than those in central and southern Anhui（ χ2=107.858 and 566.202，5.950 and 142.223，39.254 and 289.137，135.402 and 449.114，39.142 and 185.114， P<0.05 or <0.01），and the detection rates in central Anhui were higher than those in southern Anhui（ χ2=272.031，102.717，162.409，118.891 and 66.889，all P<0.001）. The detection rates of CRKP，CRPA and thirdgeneration cephalosporinresistant Klebsiella pneumoniae（3GC-R-KP）in central Anhui were the highest（16.7%，21.7% and 32.0%，respectively），which were higher than those in northern and southern Anhui（ χ2=229.656 and 439.377，156.599 and 65.818，77.386 and 232.568，all P<0.001）. The detection rates of CREC，3GC-R-EC and QREC were the highest in the elderly（2.2%，54.0% and 56.4%，respectively），which were higher than those in children and adults（ χ2=8.034 and 13.150，17.032 and 103.437，438.353 and 183.099，all P<0.01）. The detection rates of CRKP and 3GC-R-KP in neonates were the highest（20.6% and 56.9%，respectively），which were significantly higher than those in children，adults and the elderly（ χ2=38.869，8.337 and 7.921；65.517，55.525 and 49.214，all P<0.01），and the detection rate of 3GC-R-KP in the elderly was higher than that in children and adults（ χ2=14.122 and 7.501，both P<0.01）. The detection rates of CRAB complex，CRPA，CREC，CRKP and 3GC-R-KP in tertiary hospitals were higher than those in secondary hospitals（ χ2=25.606，16.501，5.820，33.116 and 117.086， P<0.05 or <0.01）. Except for MRSA，vancomycin-resistant Enterococcus faecium and QREC，the detection rates of major drug-resistant bacteria in intensive care unit（ICU）were the highest（all P<0.001）. From 2019 to 2024，the detection rates of MRSA，MRCNS，CRKP，CRAB complex and CRPA all showed a slow decreasing trend（ χ2=42.319，122.779，340.381，83.512 and 81.668，all P<0.001）. Conclusions:The situation of antimicrobial resistance in Anhui province shows a downward trend，but it is still serious，especially in northern and central Anhui. It is necessary to pay attention to the bacterial resistance particularly for the elderly，newborns，children and ICU.

OBJECTIVE To explore the molecular mechanism of Xijiao Dihuang Decoction(XJDHT)in inhibiting inflammatory response in sepsis based on network pharmacology,molecular docking and in vitro and in vivo experiments.METHODS Active com-ponents of XJDHT were screened using the TCMSP and HERB databases.Sepsis-related targets and histone H3K36 trimethylation(H3K36me3)-associated targets were retrieved from GeneCard,OMIM,and DisGeNet databases.A protein-protein interaction(PPI)network was constructed using the STRING database,and core targets were identified via Cytoscape 3.9.1.Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analyses were performed to predict potential mechanisms.Mo-lecular docking validated ligand-receptor binding affinity.A cecal ligation and puncture(CLP)model was established in mice to evalu-ate 24-hour sepsis scores(MSS)and survival rates.Blood routine parameters were analyzed using an automated hematology analyzer.Serum IL-1β and TNF-α levels were measured by ELISA.Liver histopathology was assessed via HE staining,and H3K36me3 expression in Kupffer cells was detected by immunofluorescence.In vitro,LPS-induced THP-1 cells were used as an in-flammatory model.ChIP-qPCR evaluated H3K36me3 enrichment at IL-1β and TNF-α gene loci.Western blot analyzed HIF-1α,EGFR,and AKT1 pathway proteins.RESULTS A total of 28 active components of XJDHT were identified,corresponding to 987 gene targets,with 189 overlapping sepsis-related targets.Core targets included TNF,IL1B,and GAPDH.Enriched pathways includ-ed EGFR tyrosine kinase inhibitor resistance.Molecular docking confirmed strong binding between core components and key targets.In vivo,compared to the sham group,the CLP group exhibited significantly reduced 24-hour survival(P<0.01),elevated MSS(P<0.01),immune imbalance,and increased serum IL-1β and TNF-α levels(P<0.01).High-and low-dose XJDHT intervention im-proved survival(P<0.01),reduced MSS(P<0.01),restored immune homeostasis,and dose-dependently suppressed IL-1β and TNF-α(P<0.01).CLP mice showed elevated H3K36me3 in Kupffer cells and severe hepatic inflammation,while XJDHT dose-de-pendently reduced H3K36me3(P<0.05)and attenuated liver injury.In peritoneal macrophages,CLP upregulated H3K36me3,IL-1β,TNF-α,HIF-1α,p-AKT1/AKT1,and EGFR(P<0.01),which were reversed by XJDHT(P<0.05,P<0.01).In vitro,LPS increased H3K36me3 and IL-1β and TNF-α expression(P<0.01),with ChIP-qPCR confirming H3K36me3 enrichment at IL-1β lo-ci(P<0.01).Treatment with 15%XJDHT-containing serum for 24 h reduced H3K36me3(P<0.01),diminished its recruitment to IL-1β loci(P<0.01),and inhibited LPS-induced activation of EGFR,HIF-1α,and p-AKT1/AKT1(P<0.05,P<0.01).HIF-1α agonist Dimethyloxallyl Glycine(DMOG)further validated that XJDHT suppressed H3K36me3-mediated epigenetic remodeling via HIF-1α-related pathways.CONCLUSION XJDHT inhibits inflammatory responses,regulates immune homeostasis,and improves sepsis prognosis,potentially by modulating H3K36me3 epigenetic modifications at IL-1β loci.

OBJECTIVE: To describe survival trends and global patterns of esophageal cancer (EC) using survival data from population-based cancer registries. METHODS: We systematically searched PubMed, EMBASE, Web of Science, SEER, and SinoMed databases for articles published up to 31 December 2023. Eligible EC survival estimates were evaluated according to country or region, period, sex, age group, pathology, and disease stage. RESULTS: After 2010, Jordan exhibited the highest age-standardized 5-year relative survival rates (RSRs)/net survival rates (NSRs) at 41.1% between 2010 and 2014, while India had the lowest, at 4.1%. Survival rates generally improved with diagnostic age across most countries, with significant increases in South Korea and China, of 12.7% and 10.5% between 2000 and 2017, respectively. Survival was higher among women compared to men, ranging from 0.4%-10.9%. Survival rates for adenocarcinoma and squamous cell carcinoma were similar, differing by about 4%. In China, the highest age-standardized RSRs/NSRs was 33.4% between 2015 and 2017. Meanwhile, the lowest was 5.3%, in Qidong (Jiangsu province) between 1992-1996. CONCLUSION Global EC survival rates have improved significantly in recent decades, but substantial geographical, sex, and age disparities still exist. In Asia, squamous cell carcinoma demonstrated superior survival rates compared to adenocarcinoma, while the opposite trend was observed in Western countries. Future research should clarify the prognostic factors influencing EC survival and tailor prevention and screening strategies to the changing EC survival patterns.
Humans ; Esophageal Neoplasms/mortality* ; Registries ; Male ; Female ; Survival Analysis ; Middle Aged ; Survival Rate ; Aged ; Global Health

Varicocele (VC) is a common cause of male infertility, yet there is a lack of molecular information for VC-associated male infertility. This study investigated alterations in the seminal plasma metabolomic and lipidomic profiles of infertile male VC patients. Twenty infertile males with VC and twenty-three age-matched healthy controls (HCs) were recruited from Peking Union Medical College Hospital (Beijing, China) between October 2019 and April 2021. Untargeted metabolite and lipid profiles from seminal plasma were analyzed using mass spectrometry. Four hundred and seventy-six metabolites and seventeen lipids were significantly different in infertile male VC patients compared to HCs. The top enriched pathways among these significantly different metabolites are protein digestion and absorption, aminoacyl-transfer RNA (tRNA) biosynthesis, and biosynthesis of amino acids. Different key lipid species, including triglyceride (TG), diacylglycerol (DG), ceramides (Cer), and phosphatidylserine (PS), varied between VC and HC groups. The distinct metabolites and lipids were moderately correlated. DL-3-phenyllactic acid is a potential diagnostic biomarker for VC-related male infertility (area under the curve [AUC] = 0.893), positively correlating with sperm count, concentration, and motility. Furthermore, DL-3-phenyllactic acid is the only metabolite shared by all four comparisons (VC vs HC, VC-induced oligoasthenospermia [OAS] vs VC-induced asthenospermia [AS], OAS vs HC, and AS vs HC). DL-3-phenyllactic acid significantly decreased in OAS than AS. Metabolite-targeting gene analysis revealed carbonic anhydrase 9 (CA9) might be the strongest candidate associated with the onset and severity of VC. The seminal plasma metabolite and lipid profiles of infertile males with VC differ significantly from those of HCs. DL-3-phenyllactic acid could be a promising biomarker.
Humans ; Male ; Varicocele/complications* ; Infertility, Male/etiology* ; Semen/metabolism* ; Lipidomics ; Adult ; Metabolomics ; Case-Control Studies ; Biomarkers/metabolism*