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.

Glycogen synthase 1 (GYS1) is the rate-limiting enzyme responsible for glycogen synthesis in skeletal muscle, heart, brain, and other extrahepatic tissues, playing a central role in systemic energy homeostasis. The human GYS1 gene maps to chromosome 19q13.33, comprises 16 exons, and encodes a 737-amino-acid polypeptide that is highly conserved across mammals. GYS1 activity is subject to multilayered and precisely coordinated regulation. At the transcriptional level, the GYS1 promoter contains a hypoxia response element (HRE) that mediates HIF-1α-dependent induction under low-oxygen conditions, as well as a muscle-specific enhancer harboring MEF2 and MyoD binding sites that confers tissue-restricted expression. At the post-translational level, a hierarchical phosphorylation cascade serves as the primary activity switch: glycogen synthase kinase 3β (GSK3β) sequentially phosphorylates four C-terminal serine residues following casein kinase II priming, while protein kinase A (PKA) and AMP-activated protein kinase (AMPK) provide parallel inhibitory inputs at both N- and C-terminal sites. Dephosphorylation and reactivation are mediated by protein phosphatase 1 (PP1) through tissue-specific glycogen-targeting regulatory subunits such as PPP1R3A and PPP1R3B, which anchor PP1 to glycogen particles and direct its activity toward GYS1. The allosteric activator glucose-6-phosphate (G6P) binds at the dimer interface, simultaneously enhancing catalytic efficiency and promoting dephosphorylation susceptibility, thereby establishing a feed-forward activation loop that couples substrate availability to glycogen synthesis. Beyond phosphorylation, GYS1 is regulated by ubiquitination (mediated by the E3 ligase PJA1), acetylation, O-linked β-N-acetylglucosamine (O-GlcNAc) modification, and SUMOylation, which collectively modulate protein stability, subcellular localization, and protein-protein interactions. Epigenetic mechanisms, including CpG island methylation and histone acetylation dynamics, govern chromatin accessibility at the GYS1 locus, while muscle-specific microRNAs such as miR-1 and miR-206 fine-tune GYS1 expression at the post-transcriptional level. Dysregulation of GYS1 has been identified as a central pathogenic driver in a spectrum of human diseases. In inherited glycogen storage disorders—including Lafora disease, adult polyglucosan body disease (APBD), and Pompe disease—loss of upstream regulatory control leads to GYS1 hyperactivation and the accumulation of structurally abnormal or excessive glycogen, resulting in progressive neurodegeneration, myopathy, and multiorgan dysfunction. In type 2 diabetes mellitus (T2DM), impaired insulin signaling through the PI3K-AKT-GSK3β axis maintains GYS1 in a hyperphosphorylated inactive state in skeletal muscle, compromising postprandial glucose disposal and exacerbating hyperglycemia. In oncology, GYS1 exhibits context-dependent roles across multiple cancer types. In hepatocellular carcinoma, FMO2⁺ cancer-associated fibroblasts stabilize GYS1 by competitively inhibiting PJA1-mediated ubiquitination, and stabilized GYS1 subsequently activates NF‑κB/CCL19 signaling to promote tertiary lymphoid structure formation and enhance anti-PD-1 immunotherapy responsiveness. In clear cell renal cell carcinoma, GYS1 promotes tumor progression through non-canonical NF‑κB pathway activation via the scaffold protein RPS27A. In triple-negative breast cancer, GYS1 has been identified as a trigger of disulfidptosis and an activator of NF-κB signaling through non-enzymatic facilitation of IκBα degradation. In colorectal cancer, mitochondrial fission deficiency drives AMPK-dependent GYS1 upregulation and glycogen accumulation as a compensatory survival mechanism, while in cervical cancer, GYS1-maintained glycogen reserves fuel the pentose phosphate pathway to generate NADPH for ROS clearance, thereby conferring cisplatin resistance in cancer stem cells. Therapeutic strategies targeting GYS1 have gained substantial momentum across these disease contexts. For glycogen storage disorders, antisense oligonucleotides, small interfering RNAs (e.g., ABX1100), and small-molecule inhibitors (e.g., MZ-101) have demonstrated preclinical and early clinical efficacy in reducing pathological glycogen accumulation. For T2DM, pharmacological activation of GYS1 through GSK3β inhibition or enhancement of PP1-mediated dephosphorylation is being explored to restore insulin-stimulated glycogen synthesis. In cancer, GYS1-directed interventions—including targeted silencing to sensitize tumors to chemotherapy and immune microenvironment modulation to enhance immunotherapy—represent emerging precision oncology approaches. This review provides a comprehensive and integrated account of GYS1 gene structure, tissue-specific distribution, regulatory networks, and pathogenic roles in metabolic disorders and malignancies, with the aim of establishing a theoretical framework for the development of GYS1-targeted precision therapies.

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.

Curcumin (Cur), a natural polyphenolic compound extracted from the rhizomes of plants belonging to the Zingiberaceae and Araceae families, has attracted considerable interest for its remarkable antioxidant, anti-inflammatory, antibacterial, and anticancer activities. Extensive studies have focused on its potential in treating various diseases, including cancers, neurodegenerative diseases, inflammation, and autoimmune disorders. However, its clinical application has been hampered by inherent physicochemical challenges, such as poor aqueous solubility, short half-life, and low bioavailability. To address these challenges, nanodrug delivery systems have been developed to improve the pharmacokinetic and pharmacodynamic profiles of curcumin, thereby enhancing its therapeutic efficacy. This review summarizes the pharmacological activities and underlying mechanisms of curcumin, encompassing its antioxidant, anti-inflammatory, anticancer, antiviral, and antibacterial effects. Furthermore, it highlights the significant advancements achieved through the development of curcumin-based nanomedicines. By synthesizing current findings, this review aims to provide insights that may inspire innovative strategies for the future design and broader applications of curcumin nanomedicines.

Objective The aim of the study is to analyze the incidence patterns and epidemiological characteristics of parasitic and vector-borne diseases in the Minhang and Jinshan districts of Shanghai, and provide evidence-based information for optimizing prevention and control measures. Methods We collected information from epidemic reports and epidemiological investigation forms for cases of parasitic and vector-borne diseases from 2005 to 2024 in Shanghai's Minhang and Jinshan districts. Descriptive epidemiological method were adopted to conduct a comparative analysis of incidence trends, epidemic characteristics, and infection sources. Results A total of 229 cases in 7 categories were reported between 2005 and 2024, with an average annual incidence rate of 0.36/100 000. The average annual incidence rate in Minhang District was significantly higher than that in Jinshan District. The most prevalent diseases were malaria and dengue fever, followed by Japanese encephalitis. Monthly case reports were available, predominantly from June to October, with a peak in July-August. A statistically significant difference was observed between the two districts in case distribution during June-October (P＜0.001), whereas no significant difference was found for July-August (P=0.331). The majority of cases were young men (111/229,48.47%), aged 20-39 years. Migrant workers/farmers constituted the largest occupational group (55/229, 24.02%). Registered residents of other provinces and cities (147/229,64.19%), and the main source of infection was overseas importation (112/229,48.91%). There were no statistically significant differences in gender and household-registration composition between the two districts (P＞0.05). Significant differences existed in age, occupation, and source of infection (P＜0.05). The imported diseases were malaria and dengue fever, with Africa and Southeast Asia being the primary source locations. Malaria was the predominant disease imported from other provinces and cities, with cases having been imported from abroad since 2012. Local infections were mainly Japanese encephalitis, followed by malaria (with the last local case reported in 2010). Cases between 2005 and 2009 were predominantly imported from other provinces and cities. The proportion of cases imported from abroad increased sharply after 2010, particularly in Minhang District. Local infections sometimes arise in Jinshan District, with Japanese encephalitis serving as the primary type. Conclusions Incidence rates of parasitic and vector-borne diseases in Minhang and Jinshan districts have generally remained low. To further reduce this disease burden, it will be necessary to strengthen joint measures for prevention and control, eliminate the environmental risk factors of vector organisms, enhance monitoring and precise control of the environment and inbound personnel to prevent the occurrence and transmission of parasitic and vector-borne diseases.

OBJECTIVE To investigate the horizontal transfer mechanisms and genetic evolutionary characteristics of virulence genes in hypervirulent Klebsiella pneumoniae(HvKP)and resistance genes in carbapenem-resistant K.pneumoniae(CRKP).METHODS The donor strain was a CRKP strain harboring both VIM and KPC resist-ance genes.The positive control was a CRKP strain containing blaIMP-4.The recipient strain was Escherichia coli J53.The horizontal transfer capability of the resistance genes was verified by plasmid conjugation assay.Fifty HvKP strains were collected from the First Affiliated Hospital of Jinan University from 2017 to 2021 and conjuga-ted with the plasmids of five CRKP strains which could mediate the transmission of drug resistance genes.The conjugants were screened by selective medium containing meropenem,and polymerase chain reaction(PCR)was used to detect the resistance and virulence genes in the conjugation-successful strains.The lethality of conjugants was verified by Galleria mellonella larval assays.RESULTS The donor CRKP strain had the ability to mediate re-sistance gene transmission.Its blaKPC gene was successfully transferred to E.coli J53,but the transference of the VIM gene failed.Five CRKP strains with the ability to mediate resistance gene transmission were screened,of which one strain carried both VIM and KPC resistance genes,and the other four strains carried the IMP-4 resist-ance gene.Only one CRKP strain with the blaIMP-4 resistance gene was successfully conjugated with HvKP,carry-ing both virulence genes(aerobactin and RmpA)and the blaIMP-4 resistance gene,with positive wire drawing test result.The Galleria mellonella larvae test showed that the conjugation-successful strain caused the death of all lar-vae within 24 hours.CONCLUSIONS In the hospital environment,CRKP and HvKP can form"superbugs"with both drug resistance and high virulence through plasmid conjugation,posing a severe challenge to clinical an-ti-infection treatment.It is necessary to strengthen the prevention and control of hospital-acquired infections.

[Purpose]To analyze the results of breast cancer screening among women aged 45～74 in Chongqing from 2012 to 2022 and compare the risk of breast cancer among women with differ-ent characteristics.[Methods]The Urban Cancer Early Diagnosis and Treatment Program was con-ducted in Chongqing from 2012 to 2022,female residents aged 45～74 years old participated in breast cancer screening.The participants who were assessed as at high risk of breast cancer in the preliminary screening were advised to receive ultrasonography and mammography examination in designated hospitals.The study population was followed up annually to obtain information on their health outcomes.The high risk rate of breast cancer,compliance of further examination,the inci-dence density and breast cancer risk were calculated.[Results]A total of 207 891 women com-pleted the questionnaires survey and risk assessment,and 35 947 were assessed as the individuals with high risk of breast cancer with a high risk rate of 17.29％.Among them 14 713 received the imaging screening with a compliance rate of 40.93％.After a mean follow-up of(5.43±3.01)years,847 cases of breast cancer were diagnosed with a cumulative incidence rate of 407.43/105,an in-cidence density of 75.03/105 person-years(95％CI:70.15/105～80.26/105 person-years).Cox pro-portional hazards regression showed that the risk of breast cancer was higher in obese women than that in normal weight women(HR=1.26,95％CI:1.00～1.59);the risk of breast cancer was signifi-cantly higher in those with family history of breast cancer than that in those without family history(HR=1.69,95％CI:1.36～2.09).Compared with non-high-risk groups of breast cancer,the risk of breast cancer was increased in high-risk individuals who were screened or not screened(HR=1.36,95％CI:1.06～1.73 and HR=1.26,95％CI:1.01～1.56).[Conclusion]The breast cancer screening program combining primary risk assessment with ultrasonography and mammography for the high-risk groups can improve the detection rate,and the compliance rate of imaging screening need to be improved in the future and make accurate screening for people with high risk of breast cancer.

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:To establish a quality control method for the standard decoction of Polygoni Avicularis Herba.Methods:Totally 12 batches of decoction pieces from different origins were collected, the standard decoction was prepared and the quality evaluation method was established, the content of index components in the decoction pieces and the standard decoction was determined with HPLC, the index components, solution pH and other parameters were calculated, and the similarity analysis was carried out against the fingerprints.Results:The total content of myricetin in 12 batches of decoction pieces was >0.12%, and the content of myricetin in the standard decoction was >0.03%, which met the standard of the 2020 edition of the Chinese Pharmacopoeia. The pH value was 5.1-5.5, the transfer rate of myricetin components ranged from 50.0%-106.3%, and the fingerprint study showed that there were 7 common peaks. The similarity analysis results indicated that the standard decoction of 12 batches of decoction pieces of Polygoni Avicularis Herba had good consistency.Conclusion:The preparation process is stable and feasible in line with the traditional decoction preparation method, and can be used for the research and quality evaluation of the standard decoction.

Objective To explore the relationship between dynamic contrast-enhanced magnetic resonance imaging(DCE-MRI)and clinical pathological features of invasive breast cancer and lymphovascular invasion(LVI).Methods Imaging and clinical pathological data were retrospectively collected from 508 patients with invasive breast cancer who underwent breast DCE-MRI at the First Medical Center of Chinese PLA General Hospital from January 2019 to August 2021.Patients were divided into the LVI-positive(LVI+)group(n=79)and LVI-negative(LVI-)group(n=429)based on postoperative pathological results.Univariate and multivariate logistic regression analyses were used to identify risk factors for LVI.Results Compared with LVI-group,LVI+group had a higher proportion of patients aged<45 years(44.3%vs.27.0%,P=0.002),non-mass-like enhancement(NME)(31.7%vs.17.7%,P=0.004),Ki-67 expression rate(40.0%vs.30.0%,P<0.001),high Ki-67 expression(94.9%vs.78.1%,P=0.001),Luminal B subtype(76.0%vs.60.1%,P=0.008),and positive axillary lymph nodes rate(72.2%vs.31.5%,P<0.001),while the proportion of Luminal A subtype was lower(2.5%vs.21.5%,P<0.001).Univariate and multivariate logistic regression analyses showed that age≥45 years(OR=0.468,95%CI 0.280-0.783,P=0.004)was an independent protective factor for LVI,while NME(OR=1.987,95%CI 1.126-3.444,P=0.016)was an independent risk factor.Compared with Luminal A subtype,patients with Luminal B subtype(OR=10.482,95%CI 3.164-64.923,P=0.001),HER-2 overexpression subtype(OR=11.571,95%CI 2.755-79.341,P=0.003)and triple-negative subtypes(OR=8.433,95%CI 1.985-57.908,P=0.009)had a higher risk of LVI.Conclusions Age≥45 years is an independent protective factor for LVI,while NME is an independent risk factor.Among molecular subtypes,patients with Luminal B,HER-2 overexpression and triple-negative subtypes have a higher risk of LVI compared with the Luminal A subtype.