Malignant tumors remain one of the most critical global public threats to human health. The early diagnosis and precise therapeutic interventions are pivotal for improving patient survival rates and prognosis. Gold nanoclusters (Au NCs), distinguished by their ultra-small size (<3 nm), tunable optical properties, and exceptional biocompatibility, have emerged as transformative agents in precision oncology. This comprehensive review systematically summarizes the multifaceted applications of Au NCs in malignant tumor treatment. We discuss their roles as follows. (1) Intelligent delivery vehicles for targeted chemotherapy and controlled release through surface functionalization. (2) Therapeutic agents for chemodynamic therapy (CDT). This capability stems from their intrinsic enzyme-like catalytic activity or potent thioredoxin reductase (TrxR) inhibitory function, which disrupts the intracellular redox homeostasis and effectively activates downstream apoptotic pathways.(3) Direct therapeutic agents are characterized by their energy conversion capabilities: they can either convert absorbed light into heat to directly kill cancer cells, or transfer that photon energy to surrounding oxygen molecules to generate cytotoxic reactive oxygen species (ROS), leading to cell apoptosis or necrosis. (4) Potent radiosensitizers that enhance radiotherapy efficacy by enhancing localized radiation dose and promoting ROS generation. This review systematically summarizes the recent advances in Au NCs as intelligent delivery systems, direct chemotherapeutic agents, phototherapeutic agents, and efficient radiosensitizers in tumor treatment, elucidating how Au NCs overcome traditional therapeutic limitations through synergistic strategy. It establishes a robust theoretical foundation for next-generation nanotheranostic platforms. However, the translation of laboratory findings into functional clinical technologies confronts three significant challenges. First, although researchers can synthesize atomically precise Au NCs, achieving large-scale production of batches with completely consistent structure, size, and surface chemistry remains extremely challenging. To effectively control the final synthetic product, a deep understanding of the characteristics and formation mechanisms of Au NCs is essential. The traditional “trial-and-error” experimental approach faces inherent limitations when dealing with vast combinations of variables, which is time-consuming, labor-intensive, and struggles with systematic exploration and reproducibility. Machine learning has emerged as a powerful tool to bridge fundamental research and clinical application, which can guide experiments in reverse by predicting synthesis success through data mining and multi-variable analysis. In the future, we anticipate to achieve precise prediction and on-demand design of Au NCs’ structure and properties. Secondly, a systematic framework for evaluating the in vivo pharmacokinetics and long-term toxicity of Au NCs is absent. To address this gap, it is crucial to develop advanced imaging methodologies and integrated theranostic platforms. Au NCs, serving as both a therapeutic core and a highly promising photoluminescent material, are key to constructing such platforms through integration with other agents. These multifunctional systems are designed to achieve optimal synergistic therapy by combining multiple treatment modalities. Finally, the investigation of Au NCs is still largely confined to preclinical cellular and animal studies. Progress necessitates comprehensive clinical research to rigorously assess their safety and efficacy across a range of human cancer models, thereby ensuring broad clinical applicability. In summary, Au NCs-based platforms hold immense promise for translation into clinical anticancer therapy.

Cyclic GMP-AMP synthase (cGAS), a pivotal molecule in innate immunity, has emerged as a keypoint in interdisciplinary research at the intersection of basic immunology and tumor biology. As a cytosolic nucleic acid sensor, cGAS is primarily characterized by its capacity to recognize double-stranded DNA (dsDNA) in the cytosol. Upon binding to dsDNA, cGAS undergoes a conformational change that promotes its dimerization and subsequent enzymatic activation. Once activated, it catalyzes the synthesis of the second messenger 2',3'-cGAMP from ATP and GTP. cGAMP then binds to the adaptor protein STING, which resides on the endoplasmic reticulum (ER) membrane. The binding process triggers STING to traffic from the ER to the Golgi apparatus, where it is phosphorylated by the kinase TBK1. Phosphorylated STING serves as a docking site for the transcription factor IRF3, facilitating its phosphorylation by TBK1. Once phosphorylated, IRF3 forms dimers and translocates to the nucleus, where it drives the expression of type I interferons and pro-inflammatory cytokines, initiating a potent antimicrobial state. The DNA-sensing mechanism of cGAS is inherently non-selective regarding the origin of its ligand. It readily detects exogenous DNA from invading pathogens, thereby playing an indispensable role in host defense against microbial infections. However, this same mechanism also enables cGAS to recognize self-DNA that leaks from the nucleus or mitochondria into the cytosol under various cellular stress conditions. While critical for immunity, the recognition of self-dsDNA by cGAS can disrupt cellular homeostasis and trigger aberrant inflammatory responses. The loss of self-tolerance can precipitate or exacerbate the pathogenesis of autoimmune disorders such as systemic lupus erythematosus (SLE) and Aicardi-Goutières syndrome (AGS), highlighting the dual role of cGAS as both a sentinel for infection and a potential driver of autoimmune pathology. Notably, the subcellular localization of cGAS is not still. Increasing recent researches have revealed that cGAS is also abundant within the nucleus, challenging the traditional view of it solely as a cytosolic nucleic acid sensor. Within the nucleus, cGAS exhibits non-canonical functions that are distinct from its canonical immunological role. First, cGAS exists in a state of stringent immunological silence in the nucleus, with mechanisms involving its competitive binding to histones and its post-translational modifications which block the activation of cGAS enzymatic activity, thus, effectively preventing it from mounting an autoimmune attack on genomic DNA. Second, cGAS plays a critical role in maintaining genomic stability. Upon DNA damage, cGAS is rapidly recruited to the lesion site and participates in the DNA damage repair process. Moreover, under conditions of DNA replication stress, cGAS contributes to the stabilization of replication forks, preventing the cell from entering a state of uncontrolled hyper-replication. Consequently, in light of the dual role of cGAS in both immune regulation and tumor development, the development of small-molecule drugs targeting cGAS holds significant therapeutic promise. This review summarizes the structural characteristics of cGAS and its canonical function as a pattern recognition receptor in the cytosol, including the types of pathogens it recognizes and the autoimmune responses resulting from erroneous recognition of self-DNA. It then focuses on its emerging non-canonical functions within the nucleus, detailing its nucleocytoplasmic shuttling, the mechanisms underlying its nuclear immune quiescence, and its role in mediating DNA damage repair and replication fork stabilization. Finally, the review discusses the progress and application prospects of small-molecule drugs targeting cGAS for the treatment of autoimmune diseases and cancer.

Cyclic GMP-AMP synthase (cGAS), a pivotal molecule in innate immunity, has emerged as a keypoint in interdisciplinary research at the intersection of basic immunology and tumor biology. As a cytosolic nucleic acid sensor, cGAS is primarily characterized by its capacity to recognize double-stranded DNA (dsDNA) in the cytosol. Upon binding to dsDNA, cGAS undergoes a conformational change that promotes its dimerization and subsequent enzymatic activation. Once activated, it catalyzes the synthesis of the second messenger 2',3'-cGAMP from ATP and GTP. cGAMP then binds to the adaptor protein STING, which resides on the endoplasmic reticulum (ER) membrane. The binding process triggers STING to traffic from the ER to the Golgi apparatus, where it is phosphorylated by the kinase TBK1. Phosphorylated STING serves as a docking site for the transcription factor IRF3, facilitating its phosphorylation by TBK1. Once phosphorylated, IRF3 forms dimers and translocates to the nucleus, where it drives the expression of type I interferons and pro-inflammatory cytokines, initiating a potent antimicrobial state. The DNA-sensing mechanism of cGAS is inherently non-selective regarding the origin of its ligand. It readily detects exogenous DNA from invading pathogens, thereby playing an indispensable role in host defense against microbial infections. However, this same mechanism also enables cGAS to recognize self-DNA that leaks from the nucleus or mitochondria into the cytosol under various cellular stress conditions. While critical for immunity, the recognition of self-dsDNA by cGAS can disrupt cellular homeostasis and trigger aberrant inflammatory responses. The loss of self-tolerance can precipitate or exacerbate the pathogenesis of autoimmune disorders such as systemic lupus erythematosus (SLE) and Aicardi-Goutières syndrome (AGS), highlighting the dual role of cGAS as both a sentinel for infection and a potential driver of autoimmune pathology. Notably, the subcellular localization of cGAS is not still. Increasing recent researches have revealed that cGAS is also abundant within the nucleus, challenging the traditional view of it solely as a cytosolic nucleic acid sensor. Within the nucleus, cGAS exhibits non-canonical functions that are distinct from its canonical immunological role. First, cGAS exists in a state of stringent immunological silence in the nucleus, with mechanisms involving its competitive binding to histones and its post-translational modifications which block the activation of cGAS enzymatic activity, thus, effectively preventing it from mounting an autoimmune attack on genomic DNA. Second, cGAS plays a critical role in maintaining genomic stability. Upon DNA damage, cGAS is rapidly recruited to the lesion site and participates in the DNA damage repair process. Moreover, under conditions of DNA replication stress, cGAS contributes to the stabilization of replication forks, preventing the cell from entering a state of uncontrolled hyper-replication. Consequently, in light of the dual role of cGAS in both immune regulation and tumor development, the development of small-molecule drugs targeting cGAS holds significant therapeutic promise. This review summarizes the structural characteristics of cGAS and its canonical function as a pattern recognition receptor in the cytosol, including the types of pathogens it recognizes and the autoimmune responses resulting from erroneous recognition of self-DNA. It then focuses on its emerging non-canonical functions within the nucleus, detailing its nucleocytoplasmic shuttling, the mechanisms underlying its nuclear immune quiescence, and its role in mediating DNA damage repair and replication fork stabilization. Finally, the review discusses the progress and application prospects of small-molecule drugs targeting cGAS for the treatment of autoimmune diseases and cancer.

BACKGROUND: The association between uric acid-albumin ratio (UAR) with different diseases has been evaluated before. However, the association between UAR with spontaneous reperfusion (SR) in patients with ST-segment elevation myocardial infarction (STEMI) has not been explored. METHODS: STEMI patients admitted to our department and underwent primary coronary angiography between 1^st November 2018 and 31^st December 2020 were retrospectively enrolled. The patients were divided into the SR group and the non-SR group according to the index coronary angiography results. The association between UAR and SR was evaluated by uni-variable and multi-variable logistic analysis. Receiver operating characteristic curve analysis was used to determine the optimum cut-off level of UAR in predicting SR. RESULTS: Three hundred and fifty-seven patients were finally enrolled in our study, 55 patients were divided into the SR group and 302 patients were divided into the non-SR group. In uni-variable analysis, patients with SR were older (P = 0.032), with higher red blood cell distribution width (P < 0.001) and red blood cell distribution width-to-platelet ratio (P < 0.001), higher level of C-reactive protein (P = 0.046), higher level of uric acid (P < 0.001) compared with patients without SR. Patients with SR had a lower level of platelets (P = 0.008), lower level of on-admission B-type natriuretic peptide (P < 0.001). As for the level of UAR, STEMI patients with SR had significantly higher levels of UAR compared with STEMI patients without SR [11.1 (8.9-13.4) vs. 8.3 (6.6-10.0), P < 0.001]. Further multi-variable logistic analysis reveals that UAR was the independent risk factor of SR in different models after adjusting different variables. Receiver operating characteristic analysis showed that UAR had good predictive value in SR (AUC = 0.75, 95% CI: 0.702-0.794, P < 0.01). CONCLUSIONS Our study shows that UAR is an independent risk factor for predicting SR in STEMI patients.

Objective:To explore the effects of stepped exercise rehabilitation training on cardiopulmonary function and quality of life in patients with ischemic heart disease.Methods:This randomized controlled study enrolled 110 patients with ischemic heart disease admitted to Jiangsu Province Hospital between January 2021 and December 2023.Patients were randomly divided into control group(n=53,routine intervention program)and intervention group(n=52,additional stepped exercise rehabilitation training).After 3-month intervention,cardiopulmonary function[stroke volume(SV),cardiac index(CI),forced expiratory volume in the first second(FEV1),maximum voluntary ventilation(MVV)],quality of life[China questionnaire of quality of life in patients with cardiovascular diseases(CQQC)score],exercise endurance[exercise duration(ED),peak oxygen intake(VO2peak),anaerobic threshold(AT)]and incidence of major adverse cardiovascular events(MACE)were compared between the two groups.Results:We included 53 patients[28 males(52.83％),age 40～69(56.25±7.76)years old]in control group compared to 52 patients[27 males(51.92％),age 40～71(55.25±2.40)years old]in the intervention group after 3-month intervention.Com-pared to patients in the control group,those in the intervention group had significantly higher SV[(65.46±3.58)ml vs.(61.69±3.78)ml],CI[(2.82±0.12)L·min-1·m-2 vs.(2.54±0.09)L·min-1·m-2],FEV1[(2.50±0.06)L vs.(2.31±0.06)L],MVV[(79.66±0.82)L/min vs.(77.16±1.09)L/min],CQQC score[(65.23±2.84)points vs.(47.98±3.25)points],ED[(382.62±31.19)s vs.(353.37±36.32)s],VQ2peak[(20.05±2.43)ml·kg-1·min-2 vs.(16.86±1.61)ml·kg-1·min-2]and AT[(13.34±0.83)ml·kg-1·min-2 vs.(11.46±0.89)ml·kg-1·min-2](P＜0.001 all),and significantly lower total incidence of MACE(11.54％vs.32.08％,P=0.011).Conclu-sion:Stepped exercise rehabilitation training may improve cardiopulmonary function,quality of life,and exercise endurance in patients with ischemic heart disease during the rehabilitation.

Objective:To explore the effects of stepped exercise rehabilitation training on cardiopulmonary function and quality of life in patients with ischemic heart disease.Methods:This randomized controlled study enrolled 110 patients with ischemic heart disease admitted to Jiangsu Province Hospital between January 2021 and December 2023.Patients were randomly divided into control group(n=53,routine intervention program)and intervention group(n=52,additional stepped exercise rehabilitation training).After 3-month intervention,cardiopulmonary function[stroke volume(SV),cardiac index(CI),forced expiratory volume in the first second(FEV1),maximum voluntary ventilation(MVV)],quality of life[China questionnaire of quality of life in patients with cardiovascular diseases(CQQC)score],exercise endurance[exercise duration(ED),peak oxygen intake(VO2peak),anaerobic threshold(AT)]and incidence of major adverse cardiovascular events(MACE)were compared between the two groups.Results:We included 53 patients[28 males(52.83％),age 40～69(56.25±7.76)years old]in control group compared to 52 patients[27 males(51.92％),age 40～71(55.25±2.40)years old]in the intervention group after 3-month intervention.Com-pared to patients in the control group,those in the intervention group had significantly higher SV[(65.46±3.58)ml vs.(61.69±3.78)ml],CI[(2.82±0.12)L·min-1·m-2 vs.(2.54±0.09)L·min-1·m-2],FEV1[(2.50±0.06)L vs.(2.31±0.06)L],MVV[(79.66±0.82)L/min vs.(77.16±1.09)L/min],CQQC score[(65.23±2.84)points vs.(47.98±3.25)points],ED[(382.62±31.19)s vs.(353.37±36.32)s],VQ2peak[(20.05±2.43)ml·kg-1·min-2 vs.(16.86±1.61)ml·kg-1·min-2]and AT[(13.34±0.83)ml·kg-1·min-2 vs.(11.46±0.89)ml·kg-1·min-2](P＜0.001 all),and significantly lower total incidence of MACE(11.54％vs.32.08％,P=0.011).Conclu-sion:Stepped exercise rehabilitation training may improve cardiopulmonary function,quality of life,and exercise endurance in patients with ischemic heart disease during the rehabilitation.

Objective This study aimed to investigate the potential relationship between urinary metals copper (Cu), arsenic (As), strontium (Sr), barium (Ba), iron (Fe), lead (Pb) and manganese (Mn) and grip strength. Methods We used linear regression models, quantile g-computation and Bayesian kernel machine regression (BKMR) to assess the relationship between metals and grip strength.Results In the multimetal linear regression, Cu (β=-2.119), As (β=-1.318), Sr (β=-2.480), Ba (β=0.781), Fe (β= 1.130) and Mn (β=-0.404) were significantly correlated with grip strength (P < 0.05). The results of the quantile g-computation showed that the risk of occurrence of grip strength reduction was -1.007 (95％ confidence interval:-1.362, -0.652; P < 0.001) when each quartile of the mixture of the seven metals was increased. Bayesian kernel function regression model analysis showed that mixtures of the seven metals had a negative overall effect on grip strength, with Cu, As and Sr being negatively associated with grip strength levels. In the total population, potential interactions were observed between As and Mn and between Cu and Mn (Pinteractions of 0.003 and 0.018, respectively).Conclusion In summary, this study suggests that combined exposure to metal mixtures is negatively associated with grip strength. Cu, Sr and As were negatively correlated with grip strength levels, and there were potential interactions between As and Mn and between Cu and Mn.

Objective To summarize the epidemiological and clinical features of infectious diseases of the central nervous system(CNS)by a single-center analysis.Methods A retrospective analysis was conducted on the data of 1247 cases of CNS infectious diseases diagnosed and treated in the First Medical Center of PLA General Hospital from 2001 to 2020.Results The data for this group of CNS infectious diseases by disease type in descending order of number of cases were viruses 743(59.6％),Mycobacterium tuberculosis 249(20.0％),other bacteria 150(12.0％),fungi 68(5.5％),parasites 18(1.4％),Treponema pallidum 18(1.4％)and rickettsia 1(0.1％).The number of cases increased by 177 cases(33.1％)in the latter 10 years compared to the previous 10 years(P<0.05).No significant difference in seasonal distribution pattern of data between disease types(P>0.05).Male to female ratio is 1.87︰1,mostly under 60 years of age.Viruses are more likely to infect students,most often at university/college level and above,farmers are overrepresented among bacteria and Mycobacterium tuberculosis,and more infections of Treponema pallidum in workers.CNS infectious diseases are characterized by fever,headache and signs of meningeal irritation,with the adductor nerve being the more commonly involved cranial nerve.Matagenomic next-generation sequencing improves clinical diagnostic capabilities.The median hospital days for CNS infectious diseases are 18.00(11.00,27.00)and median hospital costs are ￥29,500(￥16,000,￥59,200).The mortality rate from CNS infectious diseases is 1.6％.Conclusions The incidence of CNS infectious diseases is increasing last ten years,with complex clinical presentation,severe symptoms and poor prognosis.Early and accurate diagnosis and standardized clinical treatment can significantly reduce the morbidity and mortality rate and ease the burden of disease.

The advantages of fluorescence detection of uric acid were introduced compared to the traditional detection methods.The preparation process,detection principle and performance of organic,inorganic and organic-inorganic hybrid fluorescent probes were reviewed.The advantages and disadvantages of kinds of fluorescent probes were analyzed when used for uric acid detection,and the futural directions were pointed out for related research.[Chinese Medical Equipment Journal,2024,45(6):93-104]

Aim To explore the effect of serum contai-ning Duhuo Jisheng Decoction on the proliferation,ap-optosis and inflammation of fibroblast-like synoviocytes(FLS)induced by tumor necrosis factor-α(TNF-α)in rheumatoid arthritis(RA)and to reveal the under-lying mechanism.Methods The MH7A cells were divided into five groups:normal group(10％blank se-rum),model group(10 μg·L-1 TNF-α+10％blank serum),Duhuo Jisheng Decoction low(10 μg·L-1 TNF-α+2.5％drug-containing serum+7.5％blank serum),medium(10 pg·L-1 TNF-α+5％drug-con-taining serum+5％blank serum),high(10 μg·L-1 TNF-α+10％drug-containing serum)dose group.The concentration of serum containing Duhuo Jisheng Decoction was screened by MTT method.Cell prolifer-ation was detected using EdU staining.The expression of proliferation marker Ki67 was detected using immu-nofluorescence staining.The apoptosis rate was meas-ured by flow cytometry.The contents of IFN-γ,IL-4,IL-6 and IL-10 in each group were detected by ELISA.The mRNA and protein expression of Bax,Bcl-2,caspase-3 and TLR4/MyD88/NF-κB signaling pathway were detected by RT-qPCR and Western blot.Results Compared with the normal group,the cell prolifera-tion activity of the model group significantly increased,and the level of apoptosis decreased.The content of IFN-γ and IL-6 increased,and the content of IL-4 and IL-10 decreased.The TLR4/MyD88/NF-κB signaling pathway was activated.After the intervention of low,medium and high dose groups of serum containing Du-huo Jisheng Decoction,it could effectively improve the abnormal proliferation of cells and enhance apoptosis.At the same time,it inhibited the inflammatory re-sponse and the activation of TLR4/MyD88/NF-κB sig-naling pathway.Conclusions The serum containing Duhuo Jisheng Decoction can inhibit the abnormal pro-liferation of RA-FLS induced by TNF-α and the secre-tion of pro-inflammatory factors,and enhance apoptosis and anti-inflammatory levels.The mechanism may be related to the regulation of TLR4/MyD88/NF-κB sig-naling pathway.