Cuproptosis, a recently discovered form of regulated cell death involving copper ion metabolism, has emerged as a promising approach for tumor therapy. This pathway not only directly eliminates tumor cells but also promotes immunogenic cell death (ICD), reshaping the tumor microenvironment (TME) and initiating robust anti-tumor immune responses. However, translating cuproptosis-based therapies into clinical applications is hindered by challenges, including complex metabolic regulation, TME heterogeneity, and the precision required for effective drug delivery. To address these limitations, nanoparticles offer transformative solutions by providing precise delivery of cuproptosis-inducing agents, controlled drug release, and enhanced therapeutic efficacy through simultaneous modulation of metabolic pathways and immune responses. This review systematically discusses recent advancements in nanoparticle-based cuproptosis delivery systems, highlighting nanoparticle design principles and their synergistic effects when integrated with other therapeutic modalities such as ICB, PTT, and CDT. Furthermore, we explore the potential of cuproptosis-based nanomedicine for personalized cancer treatment by emphasizing strategies for TME stratification and therapeutic optimization tailored to patient profiles. By integrating current insights from metabolic reprogramming, tumor immunotherapy, and nanotechnology, this review aims to facilitate the clinical translation of cuproptosis nanomedicine and significantly contribute to the advancement of precision oncology.

Objective:Mendelian randomization analysis (MR) was used to investigate the causal association between nine cathepsins and cholelithiasis.Methods:Single nucleotide polymorphism (SNP) sites closely associated and mutually independent with nine cathepsins and cholelithiasis were screened out from the Genome-Wide Association Study database and the FinnGen Biobank database, respectively. SNP corresponding to exposure factors were selected as instrumental variables. Two-sample bidirectional MR analysis was conducted with methods of inverse variance weighted (IVW), weighted median and MR-Egger regression. Additionally, multivariable Mendelian randomization (MVMR) was conducted to estimate the direct effect of cathepsins on cholelithiasis. Cochran's Q test, MR-PRESSO method and MR Egger regression were used to evaluate the levels of heterogeneity and pleiotropy. And the leave-one-out method was performed for the sensitivity analysis. Results:The univariable Mendelian randomization analysis results indicated that elevated cathepsin B levels increased the overall risk of cholelithiasis (IVW: OR=1.054, 95% CI: 1.025-1.083, P<0.001). The reverse MR analyses did not support a causal effect of cholelithiasis on cathepsin B (IVW: OR=0.998, 95% CI: 0.920-1.083, P=0.969). A multivariable analysis showed that elevated cathepsin B levels were still strongly associated with an increased risk of cholelithiasis (IVW: OR=1.038, 95% CI: 1.003-1.073, P=0.031). None evidence of significant pleiotropy and heterogeneity was observed, which was verified by sensitivity analysis. Conclusion:Cathepsin B may serve as a marker for cholelithiasis, and has important guiding significance in cholelithiasis treatment.

BACKGROUND: Spatiotemporal disparities exist in the disease burden of non-communicable diseases (NCDs) attributable to kidney dysfunction, which has been poorly assessed. The present study aimed to evaluate the spatiotemporal trends of the global burden of NCDs attributable to kidney dysfunction and to predict future trends. METHODS: Data on NCDs attributable to kidney dysfunction, quantified using deaths and disability-adjusted life-years (DALYs), were extracted from the Global Burden of Diseases Injuries, and Risk Factors (GBD) Study in 2019. Estimated annual percentage change (EAPC) of age-standardized rate (ASR) was calculated with linear regression to assess the changing trend. Pearson's correlation analysis was used to determine the association between ASR and sociodemographic index (SDI) for 21 GBD regions. A Bayesian age-period-cohort (BAPC) model was used to predict future trends up to 2040. RESULTS: Between 1990 and 2019, the absolute number of deaths and DALYs from NCDs attributable to kidney dysfunction increased globally. The death cases increased from 1,571,720 (95% uncertainty interval [UI]: 1,344,420-1,805,598) in 1990 to 3,161,552 (95% UI: 2,723,363-3,623,814) in 2019 for both sexes combined. Both the ASR of death and DALYs increased in Andean Latin America, the Caribbean, Central Latin America, Southeast Asia, Oceania, and Southern Sub-Saharan Africa. In contrast, the age-standardized metrics decreased in the high-income Asia Pacific region. The relationship between SDI and ASR of death and DALYs was negatively correlated. The BAPC model indicated that there would be approximately 5,806,780 death cases and 119,013,659 DALY cases in 2040 that could be attributed to kidney dysfunction. Age-standardized death of cardiovascular diseases (CVDs) and CKD attributable to kidney dysfunction were predicted to decrease and increase from 2020 to 2040, respectively. CONCLUSION NCDs attributable to kidney dysfunction remain a major public health concern worldwide. Efforts are required to attenuate the death and disability burden, particularly in low and low-to-middle SDI regions.
Humans ; Noncommunicable Diseases/epidemiology* ; Global Burden of Disease ; Disability-Adjusted Life Years ; Male ; Female ; Risk Factors ; Middle Aged ; Kidney Diseases/epidemiology* ; Bayes Theorem ; Adult ; Aged ; Global Health ; Quality-Adjusted Life Years

Objective To assess bacterial contamination in the indoor air and on item surface(hereinafter referred to as surface)within the pediatric outpatient departments of three tertiary hospitals,and provide reference for improving disinfection management and protecting children and medical staff.Methods A high-flow bioaerosol sampler was used to collected and monitored microorganisms from 42 indoor air samples across various surfaces of pediatric outpatient clinics within three tertiary hospitals.Additionally,surface sam-pling was employed to examine frequently touched surfaces by both medical staff and patients,with the objective of identifying bacterial colony-forming units(CFU).Results In the pediatric outpatient clinics,the B Hospital showed a significantly lower count of bacterial colonies in general air samples compared to A Hospital and C Hospital(P＜0.05).Conversely,A Hospital had a significantly lower count of bacterial colonies on frequently touched surfaces by both medical staff and patients than B Hospital and C Hospital(P＜0.05).Airborne CFU exceeded normal levels in all three hospitals.Notably,the waiting hall of A Hospital had a significantly higher concentration of airborne pathogens compared to its consultation and nebulization rooms(P＜0.05).At B Hospital,there was no significant difference in airborne pathogen levels between the consultation room and the waiting hall(P＞0.05).Meanwhile,the waiting hall and infusion room at C Hospital both had significantly higher pathogen levels than the consultation room(P＜0.05).The CFU of pathogens on sur-faces frequently contacted by patients or their family members were significantly higher at B Hospital and C Hospital than those contacted by medical staff(P＜0.05).In contrast,there was no significant difference in pathogen CFU detected on the surface of patients or fami-ly members in hospital A and that of medical staff(P＞0.05).Pathogenic bacteria,including staphylococcus aureus,bacillus cereus,and streptococcus pneumoniae,were detected in the air and on surfaces across all three hospitals,with a notable presence in consultation rooms,waiting halls,and infusion rooms.Conclusion The pediatric outpatient clinics of the three tertiary hospitals exhibit varying levels of microbial contamination,underscoring the need for vigilant and standardized management of routine disinfection practices.

Objective To assess bacterial contamination in the indoor air and on item surface(hereinafter referred to as surface)within the pediatric outpatient departments of three tertiary hospitals,and provide reference for improving disinfection management and protecting children and medical staff.Methods A high-flow bioaerosol sampler was used to collected and monitored microorganisms from 42 indoor air samples across various surfaces of pediatric outpatient clinics within three tertiary hospitals.Additionally,surface sam-pling was employed to examine frequently touched surfaces by both medical staff and patients,with the objective of identifying bacterial colony-forming units(CFU).Results In the pediatric outpatient clinics,the B Hospital showed a significantly lower count of bacterial colonies in general air samples compared to A Hospital and C Hospital(P＜0.05).Conversely,A Hospital had a significantly lower count of bacterial colonies on frequently touched surfaces by both medical staff and patients than B Hospital and C Hospital(P＜0.05).Airborne CFU exceeded normal levels in all three hospitals.Notably,the waiting hall of A Hospital had a significantly higher concentration of airborne pathogens compared to its consultation and nebulization rooms(P＜0.05).At B Hospital,there was no significant difference in airborne pathogen levels between the consultation room and the waiting hall(P＞0.05).Meanwhile,the waiting hall and infusion room at C Hospital both had significantly higher pathogen levels than the consultation room(P＜0.05).The CFU of pathogens on sur-faces frequently contacted by patients or their family members were significantly higher at B Hospital and C Hospital than those contacted by medical staff(P＜0.05).In contrast,there was no significant difference in pathogen CFU detected on the surface of patients or fami-ly members in hospital A and that of medical staff(P＞0.05).Pathogenic bacteria,including staphylococcus aureus,bacillus cereus,and streptococcus pneumoniae,were detected in the air and on surfaces across all three hospitals,with a notable presence in consultation rooms,waiting halls,and infusion rooms.Conclusion The pediatric outpatient clinics of the three tertiary hospitals exhibit varying levels of microbial contamination,underscoring the need for vigilant and standardized management of routine disinfection practices.

Objective:Mendelian randomization analysis (MR) was used to investigate the causal association between nine cathepsins and cholelithiasis.Methods:Single nucleotide polymorphism (SNP) sites closely associated and mutually independent with nine cathepsins and cholelithiasis were screened out from the Genome-Wide Association Study database and the FinnGen Biobank database, respectively. SNP corresponding to exposure factors were selected as instrumental variables. Two-sample bidirectional MR analysis was conducted with methods of inverse variance weighted (IVW), weighted median and MR-Egger regression. Additionally, multivariable Mendelian randomization (MVMR) was conducted to estimate the direct effect of cathepsins on cholelithiasis. Cochran's Q test, MR-PRESSO method and MR Egger regression were used to evaluate the levels of heterogeneity and pleiotropy. And the leave-one-out method was performed for the sensitivity analysis. Results:The univariable Mendelian randomization analysis results indicated that elevated cathepsin B levels increased the overall risk of cholelithiasis (IVW: OR=1.054, 95% CI: 1.025-1.083, P<0.001). The reverse MR analyses did not support a causal effect of cholelithiasis on cathepsin B (IVW: OR=0.998, 95% CI: 0.920-1.083, P=0.969). A multivariable analysis showed that elevated cathepsin B levels were still strongly associated with an increased risk of cholelithiasis (IVW: OR=1.038, 95% CI: 1.003-1.073, P=0.031). None evidence of significant pleiotropy and heterogeneity was observed, which was verified by sensitivity analysis. Conclusion:Cathepsin B may serve as a marker for cholelithiasis, and has important guiding significance in cholelithiasis treatment.

Objective:To analyze the clinical phenotype and molecular pathogenesis of nine patients with hereditary factor Ⅴ (FⅤ) deficiency.Methods:Nine patients with hereditary FⅤ deficiency who were admitted to the Institute of Hematology and Blood Diseases Hospital from April 1999 to September 2019 were analyzed. The activated partial thromboplastin time, prothrombin time, and FⅤ procoagulant activity (FⅤ∶C) were measured for phenotypic diagnosis. High-throughput sequencing was employed for the F5 gene mutation screening, Sanger sequencing was adopted to confirm candidate variants and parental carrying status, Swiss-model was used for three-dimensional structure analysis, and ClustalX v.2.1 was used for homologous analysis.Results:The FⅤ∶C of the nine patients ranged from 0.1 to 10.6. Among them, eight had a hemorrhage history, with kin/mucosal bleeding as the most common symptom (three cases, 37.5%) , whereas one case had no bleeding symptom. There were five homozygotes and four compound heterozygotes. A total of 12 pathogenic or likely pathogenic mutations were detected, of which c.6100C>A/p.Pro2034Thr, c.6575T>C/p.Phe2192Ser, c.1600_1601delinsTG/p. Gln534*, c.4713C>A/p.Tyr1571*, and c.952+5G>C were reported for the first time.Conclusion:The newly discovered gene mutations enriched the F5 gene mutation spectrum associated with hereditary FⅤ deficiency. High-throughput sequencing could be an effective method to detect F5 gene mutations.

Objective To report 9 HIV-negative patients with talaromycosis marueffei (TSM)complicated by Sweet syndrome,and to analyze the relationship of the anti-interferon-γ (anti-IFN-γ)autoantibody with TSM complicated by Sweet syndrome.Methods HIV-negative patients with TSM complicated by Sweet syndrome were collected from the First Affiliated Hospital of Guangxi Medical University between 2013 and 2018.Their clinical and laboratory data were analyzed retrospectively.Meanwhile,19 HIV-positive patients with TSM and 107 health checkup examinees served as controls.Anti-IFN-γ autoantibody was detected in peripheral blood samples of the patients and controls.Results A total of 9 HIV-negative patients with TSM (5 males and 4 females) were included in this study,and the age of onset ranged from 38 to 60 years.The 9 patients all presented with disseminated infections,manifesting as long-term irregular fever,multiple lymph node enlargement,cough,emaciation and anemia.All of the 9 patients met the diagnostic criteria for classical Sweet syndrome,and microbiological examination of Sweet syndrome lesions was negative.Besides Talaromyces marneffei,6 patients also were infected with nontuberculous mycobacteria,4 with varicella-zoster virus,and 2 with Salmonella.All the 9 HIV-negative patients with TSM were positive for anti-IFN-γ autoantibody,while the 107 healthy controls and 19 HIV-positive patients with TSM were negative for anti-IFN-γ autoantibody.Conclusion Anti-IFN-γ autoantibody may be associated with HIV-negative TSM complicated by Sweet syndrome.

Objective To analyze the clinical manifestations, imaging features, histopathology and genes of cerebrotendinous xanthomatosis (CTX) to improve the understanding of clinical workers on the disease. Methods The imaging examination, histopathological and gene detection methods were synthetically applied, and the disease characteristics of two patients with CTX, admitted to our hospital in March 2018 , were analyzed. Results (1) Patient one was a 52-year-old male, with typical neurological symptoms: weakness of both lower limbs, damage of pyramidal tract and extrapyramidal system, cognitive impairment, and ataxia; non-neurological symptoms included cataract, arch foot, and Achilles tendon mass; cranial MR imaging indicated symmetrical abnormal signal of cerebellar dentate nucleus, low signal on T1WI, and slightly high and low signal intensity on T2WI/FLAIR; achilles tendon biopsy showed fibrous connective tissues with multiple xanthoma cells and multinucleated giant cells aggregation, accompanied by cholesterol crystallization. (2) Another 16-year-old male presented with cerebellar ataxia, recurrent seizures, mental and motor retardation, and congenital cataract; two heterozygous mutations of CYP27A1 gene were detected by gene detection; and the mutations were c.373-379 delCCAGTAC and c.1420C>T. Conclusion The clinical manifestations of CTX are varied; early imaging examination lacks specificity; it can be clearly diagnosed by histopathology and CYP27A1 gene detection.

Objective: To investigate the levels of NK cells and their relevant cytokines (IL-10, TGF-β and IFN-γ) in patients with primary immune thrombocytopenia (ITP) . Methods: All samples were obtained from 42 patients (22 newly diagnosed and 20 in remission) and 20 healthy volunteers. The levels of IL-10 and IFN-γ in blood serum were detected by enzyme-linked immunosorbent assay (ELISA) . The percentage of CD3^- CD56⁺ NK cell, CD3^- CD56^bright CD16^- NK cell, CD3^- CD56^dim CD16⁺ NK cell in peripheral blood lymphocyte were detected by flow cytometry. The NK cells were isolated by immunomagnetic microbeads. The mRNA expression levels of IL-10, TGF-β, and IFN-γ in NK cells were detected by real-time fluorescent quantitative PCR. Correlation between the above measured results was analyzed. Results: ① The blood serum level of IFN-γ in newly diagnosed ITP patients [ (653.0±221.6) ng/L] was higher than that in remission ITP patients [ (484.4±219.5) ng/L] and healthy control [ (390.9±253.5) ng/L] (P=0.022, P=0.001) . The blood serum level of IL-10 in newly diagnosed ITP patients was lower than that in healthy control [ (52.09±26.66) ng/L vs (79.44±38.43) ng/L, P=0.007]. ②The percentage of NK cell in newly diagnosed and remission ITP patients [ (9.53±3.93) %, (9.03±3.78) %] were significantly lower than that in healthy control [ (13.72±7.42) %] (P=0.013, P=0.007) . The ratio of CD3^- CD56^bright CD16^- NK cell/total NK cells in newly diagnosed ITP patients was higher than that in healthy control [ (6.85±4.43) % vs (4.05±2.81) %, P=0.032]. The ratio of CD3^-CD56^dim CD16^- NK cell/total NK cells in newly diagnosed ITP patients was lower than that in healthy control [ (93.14±4.43) % vs (95.94±2.81) %, P=0.032]. ③ There was no significant difference in the mRNA expression level of IFN-γ in NK cells of ITP patients and healthy control (all P>0.05) . The mRNA expression levels of IL-10 and TGF-β in NK cells in newly diagnosed ITP patients were significantly higher than that in healthy control (1.82±1.32 vs 1.02±1.03, P=0.023; 2.80±2.31 vs 1.46±1.37, P=0.028) . The ratio of CD3^-CD56^bright CD16^- NK cell/total NK cells was positively correlated with the mRNA expression levels of IL-10, TGF-β in NK cells (r=0.424, P=0.001; r=0.432, P<0.001) . Conclusion NK cells may compensate for the deficiency of the number by enhancing the secretion of negative regulation cytokines, acting as "protective" roles in the disease.