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 To explore the relationship between translocase of outer mitochondrial membrane 40（TOMM40）gene polymorphism and inflammatory status and cognitive function in patients with vascular dementia（VaD）. Methods From June 2020 to December 2022，48 patients with VaD and 40 age-matched control participants were enrolled. TOMM40_rs11556505 and IL-10-592 A/C_rs1800872 polymorphisms were measured. The cognitive function of the patients was evaluated by using the Repeatable Battery for the Assessment of Neuropsychological Status（RBANS）. Results The main effects of VaD were significant in all the analyses of the sub-scores and total score of RBANS（all P<0.001，all FDR<0.001）. TOMM40_rs11556505 polymorphism had a significant main effect on language score（F=4.524，P=0.034，Cohen f=0.08）. TOMM40×VaD had significant interaction effects on immediate memory（F=4.682，P=0.031，Cohen f=0.08）and language score（F=4.465，P=0.035，Cohen f=0.08）. The two-way multivariate analysis of covariance（IL-10×TOMM40）revealed significant interaction effects between their gene polymorphisms on visual space/structure（F=4.063，P=0.045，FDR=0.080，Cohen f=0.13），language（F=12.031，P<0.001，FDR=0.006，Cohen f=0.23），and delayed memory（F=5.118，P=0.025，FDR=0.075，Cohen f=0.23）in patients with VaD. Conclusion IL-10-592 A/C and TOMM40_rs11556505 gene polymorphisms have interaction effects on cognitive function，with their influence direction depending on each other's genotype.
Interleukin-10

OBJECTIVE: To observe change in serum growth differentiation factor 11 (GDF11) and killer cell lectin-like receptor B1 (KLRB1), to construct a nomogram model for 28-day death in patients with septic shock, and to explore its predictive value. METHODS: A prospective observational study was conducted. The patients with septic shock admitted to the emergency intensive care unit (ICU) of Cangzhou Central Hospital from September 2023 to March 2025 were selected as the septic shock group, the patients with sepsis admitted to the emergency general ward during the same period were selected as the sepsis group, and healthy individuals undergoing physical examination during the same period were selected as the control group. On the day of hospital admission or physical examination for the research subjects, the levels of serum GDF11 and KLRB1 were detected by enzyme-linked immunosorbent assay (ELISA). The patients with septic shock were divided into survival and death groups based on their 28-day survival status. The patients' gender, age, past medical history, infection site, severity of illness, mechanical ventilation, blood purification, infection indicators, biochemical indicators, coagulation function indicators, and blood lactic acid (Lac) were collected. The clinical data of the patients with septic shock between the two groups with different prognoses were compared. Multivariate Logistic regression analysis was used to screen the risk factors for 28-day death in patients with septic shock, and bivariate Pearson correlation analysis was conducted. A nomogram model was constructed based on the risk factors for 28-day death in patients with septic shock. The discrimination and calibration of the nomogram model were evaluated using the receiver operator characteristic curve (ROC curve), Hosmer-Lemeshow goodness-of-fit test, and calibration curve. The clinical utility of the model was evaluated using clinical decision curve analysis (DCA). RESULTS: A total of 168 patients in the emergency ICU were enrolled in the septic shock group, 40 patients in the emergency general ward were enrolled in the sepsis group, and 40 healthy individuals were enrolled in the control group. Compared with the healthy control group, the serum GDF11 levels in the sepsis and septic shock groups were significantly increased (μg/L: 13.09±3.51, 19.28±5.36 vs. 4.17±0.92, both P < 0.05), and the serum KLRB1 levels were significantly decreased (ng/L: 57.36±11.28, 45.52±9.07 vs. 84.19±17.16, both P < 0.05), with more significant changes in the septic shock group (both P < 0.05). Among the 168 patients with septic shock, 96 survived and 72 died within 28 days. Compared with the survival group, the serum GDF11 level in the death group was significantly increased (μg/L: 24.24±4.81 vs. 15.56±4.62, P < 0.05), and the serum KLRB1 level was significantly decreased (ng/L: 28.53±8.69 vs. 58.26±9.45, P < 0.05). There were also statistically significant differences in sequential organ failure assessment (SOFA) score, acute physiology and chronic health evaluation II (APACHEII) score, procalcitonin (PCT), activated partial thromboplastin time (APTT), D-dimer, and Lac between the two groups. Multivariate Logistic regression analysis showed that SOFA score [odds ratio (OR) = 1.96, 95% confidence interval (95%CI) was 1.38-3.65), Lac (OR = 1.38, 95%CI was 1.09-2.01), GDF11 (OR = 1.54, 95%CI was 1.21-2.33) and KLRB1 (OR = 0.64, 95%CI was 0.41-0.78) were independent risk factors for 28-day death in patients with septic shock (all P < 0.05). Bivariate Pearson correlation analysis showed that SOFA score was significantly positively correlated with Lac and GDF11 (r value was 0.37 and 0.58, respectively, both P < 0.05), and significantly negatively correlated with KLRB1 (r = -0.72, P < 0.05). A nomogram model was constructed based on the risk factors for 28-day death in patients with septic shock. ROC curve analysis showed that the area under the ROC curve (AUC) of the nomogram model for predicting 28-day death in patients with septic shock was 0.963 (95%CI was 0.929-0.990), indicating that the model had good discrimination and predictive ability. The Hosmer-Lemeshow goodness-of-fit test (χ ² = 9.578, P = 0.295) and calibration curve indicated that the predicted values of the model were in good agreement with the actual values. DCA indicated that the model provided a high net benefit for clinical decision-making. CONCLUSIONS The serum GDF11 level was significantly increased and the KLRB1 level was significantly decreased in patients with septic shock. The nomogram model based on GDF11 and KLRB1 could more accurately evaluate the 28-day death of patients with septic shock.
Humans ; Shock, Septic/blood* ; Nomograms ; Prospective Studies ; Prognosis ; Male ; Female ; Middle Aged ; Aged ; Intensive Care Units

Objective:To describe demographic,clinical and physiological characteristics,treatment between first-episode major depressive disorder(MDD)and relapse MDD,and to explore characteristics of relapse MDD.Methods:Totally 858 patients who met the diagnostic criteria for depression of the Diagnostic and Statistical Manual of Mental Disorders,Fifth Edition(DSM-5),were included by using the Mini International Neuropsychiatric Interview(MINI),Clinician-Rated Dimensions of Psychosis Symptom Severity,and Hamilton Depression Scale etc.Among them,529(58.6％)were first-episode depression and 329(36.0％)were relapsed.The differences of demographic characteristics,clinical and physiological characteristics,treatment were compared byx2test and Kruskal-Wallis rank sum test.Multivariate logistic regression was used to explore the characteristics of MDD recur-rence.Results:Compared to first-episode MDD,relapse MDD had more comorbidity(OR=2.11,95％CI:1.00-4.44),more days out of role(OR=1.26,95％CI:1.01-1.56),more history of using psychiatric drug more than one month(OR=1.41,95％CI:1.02-1.97)and electroconvulsive therapy(OR=3.23,95％CI:1.42-7.36),and higher waist-hip ratio(OR=33.88,95％CI:2.88-399.32).Conclusion:Relapse MDD has positive as-sociation with comorbidity of mental disorders,out of role,and higher waist-hip ratio.

Purpose To evaluate the diagnostic value of Chinese thyroid imaging reporting and data system(C-TIRADS)and American thyroid association(ATA)guidelines in papillary thyroid carcinoma(PTC).Materials and Methods A total of 259 patients(339 nodules)with definite pathological results after thyroid nodule surgery in the 909th Hospital of the Joint Logistic Support Force(the Affiliated Southeast Hospital of Xiamen University)from July 2019 to May 2021 were divided into benign thyroid nodule group(150 cases,210 nodules)and PTC group(109 cases,129 nodules).General data and nodule ultrasonographic characteristics of the two groups were retrospectively analyzed.Nodules were classified by the two guidelines,and were compared with surgical pathological results,the receiver operating characteristic curve was drawn to evaluate the diagnostic value of the two guidelines for PTC.Results There were statistically significant differences between the two groups in the malignant ultrasonographic features of"solid,blurred/irregular edges or extrathyroid invasion,verticality,low or very low echo,microcalcification"(χ2=123.67,132.71,103.82,4.58,137.93,all P<0.05),and most commonly seen in the PTC group.Unlike C-TIRADS,61 nodules were not clearly classified in the ATA guidelines,accounting for 17.99%(61/339).The areas under the curves of C-TIRADS and ATA guidelines were 0.952(0.924-0.972)and 0.942(0.911-0.964),with no statistically significant differences(Z=0.943,P=0.346).The optimal cutoff values of the two groups were 4b and highly suspicious malignancy,and the sensitivity,specificity and accuracy were 0.930(120/129)vs.0.822(106/129),0.857(180/210)vs.0.943(198/210),0.885(300/339)vs.0.897(300/339),respectively.There were significant differences in sensitivity and specificity(χ2=6.99,8.57,both P<0.01),C-TIRADS had the highest sensitivity,ATA guidelines had the highest specificity,but there was no significant difference in accuracy(χ2=0.24,P=0.622).Conclusion Both C-TIRADS and ATA guidelines may be highly effective in the diagnosis of PTC,but C-TIRADS can be applied to the ultrasonographic manifestations of all thyroid nodules,and is less affected by the clinical experience of sonographers,so it is easier to be promoted in clinical practice.

Objective To explore the application low of stimulation parameters of transcutaneous electrical acupoint stimulation(TEAS)and transcranial direct current stimulation(tDCS)for post-stroke movement disorders based on data mining.Methods The relevant clinical research literature was retrieved from CNKI,Wanfang Data,VIP,CBM,PubMed and Web of Science from January 2000 to May 2023.A database was set up after quality assessment.Frequency analysis,association rules and complex network analysis were used to explore the application law of core acupoints and electrical stimulation parameters.Results A total of 79 articles were included and 128 groups of data were contained.For TEAS,the core acupoints included Waiguan(TE5),Shousanli(LI10),Zusanli(ST36),Hegu(LI4),Neiguan(PC6),Yanglingquan(GB34),etc.,while the most commonly used acupoint combinations of upper limb and lower limb were Shousanli(LI10)-Waiguan(TE5)and Yanglingquan(GB34)-Zusanli(ST36).Among the electrical stimulation parameters of TEAS,the frequencies used vary widely,and 100 Hz was most commonly used,while 2 Hz TEAS was also mainly used for stimulating acupoints located on upper limbs in the treatment of flaccid paralysis.The application of other electrical stimulation parameters was relatively consistent.The bidirectional symmetrical square-wave with 200-250 μs pulse-width was used in majority of studies.The stimulus intensity was mostly determined by patient tolerance.For tDCS,stimulation electrodes were often positioned on the projection of the primary M1,and the safe stimulus intensity was mostly set as 1 to 2 mA.Conclusion In the treatment of post-stroke movement disorders,appropriate acupoints and electrical stimulation parameters of TEAS should be determined on the muscle strength and muscle tension of stroke patients at different stages after stroke,particularly the selection of electric stimulating frequency.

An increasing number of studies have shown that neuroimaging techniques, including CT- and MRI-related imaging biomarkers, are associated with the clinical outcome after intravenous thrombolysis in patients with acute ischemic stroke. Therefore, as a necessary diagnostic item for acute ischemic stroke, imaging examinations and related biomarkers have important value in predicting the outcome after intravenous thrombolysis in patients with acute ischemic stroke.

Objective:To investigate the serum levels of miR-19b and miR-744-5p in patients with non-small cell lung cancer (NSCLC), and to analyze the clinical value of miR-19b and miR-744-5p in the diagnosis of NSCLC.Methods:A total of 226 NSCLC patients (NSCLC group) and 100 healthy people (control group) admitted to Jilin Cancer Hospital from August 2019 to August 2022 were selected as research objects. Quantitative real-time PCR was used to measure and compare the serum levels of miR-19b and miR-744-5p between the NSCLC group and the control group, and the relationships between the two indicators and different clinical and pathological characteristics of NSCLC patients were analyzed. The receiver operating characteristic curve was used to analyze the clinical value of miR-19b, miR-744-5p and their joint detection in the diagnosis of NSCLC.Results:Compared with the control group, the serum miR-19b level (3.86±1.25 vs. 1.06±0.41) in the NSCLC group significantly increased ( t=21.87, P<0.001), while the miR-744-5p level (1.80±0.48 vs. 5.75±1.69) significantly decreased ( t=32.36, P<0.001). The serum miR-19b levels in NSCLC patients with pathological types of adenocarcinoma, maximum tumor diameter ≥3 cm, medium to low differentiation, stage Ⅲ-Ⅳ, and with lymph node metastasis were higher than those in squamous cell carcinoma ( t=5.94, P<0.001), maximum tumor diameter <3 cm ( t=2.65, P=0.009), well differentiation ( t=4.33, P<0.001), stageⅠ-Ⅱ ( t=12.32, P<0.001), patients without lymph node metastasis ( t=8.13, P<0.001), while miR-744-5p levels were lower than those in squamous cell carcinoma ( t=8.27, P<0.001), tumor maximum diameter <3 cm ( t=5.34, P<0.001), well differentiation ( t=6.95, P<0.001), stageⅠ-Ⅱ ( t=11.40, P<0.001), patients without lymph node metastasis ( t=10.36, P<0.001). The area under the curve (AUC) of serum miR-19b combined with miR-744-5p in the diagnosis of NSCLC was 0.914 (95% CI: 0.841-0.959), with sensitivity and specificity of 90.9% and 84.0%, respectively. AUC was significantly than that of the single indicator detection of miR-19b (AUC=0.824, 95% CI: 0.770-0.869) and miR-744-5p (AUC=0.783, 95% CI: 0.709-0.838) ( Z=2.28, P=0.021; Z=2.36, P=0.017) . Conclusion:Serum miR-19b level of NSCLC patients is increased, miR-744-5p levels is decreased, and joint detection of serum miR-19b and miR-744-5p has high clinical value in the diagnosis of NSCLC.

Objective:To explore any effect of combining robot-assisted virtual scenario training of the upper limbs with scalp acupuncture on post-stroke cognitive impairment.Methods:Ninety patients with post-stroke cognitive impairment (PSCI) were divided at random into a control group, a scalp acupuncture group and a comprehensive group, each of 30. In addition to routine health education and rehabilitation training, the scalp acupuncture group was given scalp acupuncture, while the comprehensive group was treated with scalp acupuncture and virtual scenario training with an upper limb robot. Before and after 4 weeks of the treatment, the subjects′ cognitive functioning was assessed using the Mini-mental State Examination (MMSE) and the Montreal Cognitive Assessment scale (MoCA). Ability in the activities of daily living (ADL) was quantified using the Modified Barthel Index (MBI).Results:After the intervention, significant improvement was observed in the average MMSE, MoCA and MBI scores of all three groups. The average MMSE and MBI scores of the scalp acupuncture group were then significantly higher than the control group′s averages, while the average MMSE, MoCA and MBI scores of the comprehensive group were all significantly better than those of the other two groups.Conclusion:Robot-assisted virtual scenario upper limb training combined with scalp acupuncture can significantly improve the cognition and ADL ability of PSCI patients.

AIM: To avoid the problem of retinal dissection in guinea pig large eyeball tissue sections, different methods were used to optimize the fixation effect of the posterior pole of the eyeball.METHODS: A total of 75 normal guinea pigs(2 weeks old)were randomly divided into 5 large groups. Group A(1-3 small groups), the entire eyeball was fixed with FAS, Davidson fixative 1(D1), and Davidson fixative 2(D2)for 24 h; group B(4-6 small groups), the entire eyeball was fixed with FAS, D1, and D2 for 1 h, then cut the cornea and fix it in their respective fixatives for 2 h; group C(7-9 small groups), the eyeball was fixed in FAS, D1, and D2 for 1 h, divided into left and right halves along the direction of the optic nerve, and then placed them in their respective fixation solutions for 2 h; group D(10-12 small groups), after fixation for 3 h in FAS, D1, and D2, the eyeball was divided into left and right halves along the optic nerve direction; group E(13-15 small groups), the cornea was cut after fixation for 3 h in FAS, D1, and D2. Hematoxylin-eosin(HE)staining was used to compare the fixation effect on posterior eyeball in each group.RESULTS: After fixation, the surface of the eyeballs in groups, 1-6 and 11-15 was smooth and round, with a transparent and bright color. In groups 7-10, the eyeballs were sunken, wrinkled, and deformed. The HE staining showed that the eyeball morphology of groups 1, 5, 6, 14, and 15 was significantly better than the other groups, with a regular internal tissue structure. The eyeballs of the other groups were sunken and wrinkled, and the internal tissue was curled and tangled, with severe retinal detachment. In groups 1, 5, 6, 14, and 15, the retina, choroid, and sclera tissues of group 14 were closely connected, without obvious retinal detachment, rupture, or curling. The tissue structure was clear and visible, and the cells were arranged neatly.CONCLUSION: The fixation effect of cutting the cornea after fixing guinea pig eyeball with D1 fixative for 3 h is the most ideal, and this operation method is simple and suitable for studying the related structures of the posterior pole of the eye.