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

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 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 discuss the diagnostic value of levels of growth stimulation expressed gene 2 protein(ST2),carbohydrate antigen 125(CA125),and human epididymis protein 4(HE4)in serum of the ovarian cancer patients,and to clarify their relationships with clinicopathological parameters of the ovarian cancer patients.Methods:A total of 136 patients with ovarian benign lesions or primary ovarian malignancies in our hospital confirmed by postoperative histopathology were randomly selected,including 53 cases in ovarian benign ovarian disease group and 83 cases in ovarian cancer group.Additionally,55 healthy female volunteers during the same period were enrolled as healthy control group.The fasting venous blood from all the subjects was collected on the first day of admission,and serum was retained;cyclic enhanced fluorescence immunoassay was used to detect ST2 levels of the subjects in various groups;chemiluminescence method was used to detect serum CA125 and HE4 levels of the subjects in various groups;receiver operating characteristic(ROC)curve was used to assess the diagnostic performance of each indicator;the Cut-off value and area under the ROC curve(AUC)were calculated,with AUC representing the diagnostic performance;Kendall's method was used to analyze the correlations between serum ST2 levels and TNM stage,maximum tumor diameter,distant metastasis,lymphnode metastasis,peritoneal metastasis,carcinoembryonic antigen(CEA),CA125,carbohydrate antigen 199(CA199),HE4,P53,and Kiel-67(Ki67)in the ovarian cancer patients.Results:Compared with healthy control group,the serum CA125 level of the patients in ovarian benign ovarian disease group was significantly increased(P<0.05).Compared with healthy control group and ovarian benign group,the serum levels of ST2,CA125,and HE4 of the patients in ovarian cancer group were significantly increased(P<0.05).The AUC values were 0.719(95%CI:0.616-0.822)for ST2,0.868(95%CI:0.794-0.942)for CA125,and 0.867(95%CI:0.793-0.942)for HE4.The combined detection of ST2+CA125+HE4 yielded an AUC of 0.894(95%CI:0.832-0.955).Significant differences were observed in serum ST2,CA125,and HE4 levels among ovarian cancer patients with different TNM stages,lymph node metastasis,distant metastasis,and peritoneal metastasis(P<0.05),while there were no significant differences in the patients with different ages or maximum tumor diameters(P>0.05).The ST2 level in serm of the ovarian cancer patients was positively correlated with TNM stage,distant metastasis,lymph node metastasis,peritoneal metastasis,CA125 level,HE4 level,and Ki67 level(P<0.05),but was not correlated with maximum tumor diameter,CEA,CA199 level,or P53 level(P>0.05).Conclusion:ST2,CA125,and HE4 are highly expressed in the serum of the ovarian cancer patients.Combined detection of serum ST2,CA125,and HE4 exhibits good sensitivity and specificity for ovarian cancer screening and improves diagnostic efficacy.ST2 is associated with advanced TNM stage and metastasis in ovarian cancer and may participate in the occurrence and progression of ovarian cancer.

Cholesterol,as an important component of cell membranes,plays a multifaceted role in mediating tumor immunomodulation and drug intervention.In case of cholesterol metabolic imbalance,the accumulation of cholesterol metabolic intermediates,the changes in concentrations,and the regulation of related signaling pathways can affect tumor immunity by promoting inflammation and inhibiting immune cell function.Preclinical and clinical studies have shown that controlling cholesterol metabolism can inhibit tumor growth,re-shape body immune regulation,and enhance antitumor immunity.A deep understanding of the association between immune cells and cholesterol metabolic pathways in the tumor microenvironment can help to develop novel drugs targeting cholesterol metabolism.This article reviews the multifaceted role of cholesterol and its derived metabolites in the tumor microenvironment by regulating various types of immune cells such as myeloid-derived suppressor cells,tumor-associated macrophages,dendritic cells,and T-lymphocytes,as well as the characteristics of tumor immunomodulation mediated by cholesterol metabolism and the advances in pharmaceutical re-search on improving the immune function of the body by intervening against cholesterol,in order to further provide new ideas and a thera-peutic basis for cholesterol modulation and intervention in tumor im-munotherapy.

Objective To investigate the correlation between serum levels of collagen triple helix repeat containing protein 1(CTHRC1)and galectin-10 and disease severity in patients with psoriasis vulgaris(PV).Methods From October 2021 to March 2023,a total of 105 confirmed PV patients treated in the hospital were regarded as the research objects.According to the disease severity,they were separated into a severe group(46 cases)and mild to moderate group(59 cases).Additionally,105 healthy individuals who came to the hospital for physical examination were selected as the control group.The levels of CTHRC1 and galectin-10 in serum were compared and analyzed.Multivariate Logistic regression analysis was conducted to identify the influen-cing factors for the development of severe PV in patients.Receiver operating characteristic(ROC)curve was applied to analyze the predictive value of serum CTHRC1 and galectin-10 levels for the development of severe PV in patients.Results Compared with the control group,the serum levels of CTHRC1 and galectin-10 in the severe group and mild to moderate group were significantly increased(P＜0.05).Compared with the mild to moderate group,the serum levels of CTHRC1 and galectin-10 in the severe group were significantly increased(P＜0.05).Compared with the mild to moderate group,the levels of inflammatory factors interleukin-26(IL-26),interleukin-22(IL-22),and interleukin-17(IL-17)were all increased in the severe group(P＜0.05).Ser-um IL-26,IL-22,CTHRC1,and galectin-10 levels were all influencing factors for the development of severe PV in patients(P＜0.05).The area under the curve(AUC)of serum IL-26,IL-22,CTHRC1 and galectin-10 levels for predicting the development of severe PV in patients were 0.809,0.784,0.863 and 0.874,respective-ly,the AUC predicted by the combination of the four was 0.966,and the combined prediction of the four was better than the prediction of the four separately(Z combination of the four-IL-26=3.581,Zcombination of the four-IL-22=3.285,Zcombination of the four-CTHRC1=2.671,Zcombination of the four-galectin10=2.434,P＜0.05).Conclusion The increased levels of CTHRC1 and galectin-10 in the serum of PV patients are related to the severity of the disease.

The incidence of aortic valve disease gradually increases with age,and has become an upward trend in recent years.Transcatheter aortic valve replacement(TAVR)has become the first-line treatment for aortic stenosis(AS)due to minimal surgical trauma and fast postoperative recovery.But TAVR is a complex and high-risk technology,and the operation requires multidisciplinary collaboration and a comprehensive nursing team.Nursing care is crucial during the perioperative period of TAVR.This article aims to provide a comprehensive review of perioperative nursing for TAVR patients,based on the latest research progress both domestically and internationally,in order to enhance the care of TAVR patients during the perioperative period,especially for postoperative complications.

Objective To evaluate the causal relationship between serum uric acid(SUA)level and cerebrovascular disease(CVD)by a two-sample bidirectional Mendelian randomization(MR)study.Methods Single nucleotide polymorphisms(SNPs)from Genome-Wide Association Studies(GWAS)were obtained as instrumental variables for both samples.Inverse-variance weighted(IVW)method was primarily adopted,with weighted median method,weighted mode method,and MR-Egger regression serving as supplementary approaches for sensitivity analyses to verify the robust-ness of the results.Results The forward IVW analysis results showed that increased SUA was a risk factor for stroke(OR=1.183,95％CI,1.081 to 1.295,P=2.51× 10-4),ischemic stroke(OR=1.196,95％CI,1.084 to 1.320,P=3.81 ×10-4),and large artery atherosclerotic stroke(OR=1.466,95％CI,1.134 to 1.897,P=0.004),and also a protective factor for vascular dementia(OR=0.451,95％CI,0.273 to 0.745,P=0.002)and multi-infarct dementia(OR=0.372,95％CI,0.144 to 0.959,P=0.041).The reverse IVW analysis results did not support a causal effect of genetically predicted CVD risk on SUA level.All significant results were corrected by Bonfer-roni with P value less than 0.005.Sensitivity analyses further confirmed the reliability of the study find-ings.Conclusion The MR analysis reveals positive correlations between increased SUA level and the risk of stroke,ischemic stroke and large artery atherosclerotic stroke,and negative correlations of SUA level with the risk of vascular dementia and multi-infarct dementia.

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.

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.