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.

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 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.

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 explore the correlation between neutrophil-to-lymphocyte ratio(NLR)and Behcet's disease(BD)activity.Methods A total of 103 BD patients were divided into the low activity group(0-4,61 cases)and the high activity group(5-11,42 cases)according to electronic medical record-based disease activity index(EMRAI)score.The white blood cell(WBC),neutrophil(NEU),lymphocyte(LY),platelet(PLT),red blood cell(RBC),hemoglobin(Hb),erythrocyte sedimentation rate(ESR),C-reactive protein(CRP),IgG,IgA,IgM,complement C3 and C4 were detected.NLR and platelet-to-lymphocyte ratio(PLR)were calculated.The correlation between NLR,PLR and ESR,CRP,EMRAI were analyzed.Logistic regression was used to analyze the influencing factors of BD disease activity.Receiver operating characteristic(ROC)curve was drawn to evaluate the effectiveness of NLR in judging BD disease activity.Results WBC,NEU,PLT,ESR,CRP,NLR,PLR,complement C3 and C4 in patients were higher in the high activity group than those in the low activity group(P＜0.05),and there were no significant differences in other indexes(P＞0.05).NLR was positively correlated with ESR,CRP and EMRAI in the whole group,while PLR was positively correlated with ESR,CRP and EMRAI in the whole group(P＜0.05).Logistic regression analysis showed that high NLR was a risk factor for BD disease activity(OR=1.511,95%CI:1.080-2.113,P＜0.05).ROC curve analysis showed that the area under the curve(AUC)of NLR in evaluating BD disease activity was 0.706(95%CI:0.603-0.809).Conclusion NLR is effective in judging the disease activity of BD patients,and can be used as a biological index to evaluate the disease activity of BD.

Objective To analyze the use of Chinese patent medicines containing toxic decoction pieces in Hohhot Mongolian Medicine of Traditional Chinese Medicine Hospital;To provide the basis and early warning for the monitoring of rational medication.Methods The prescriptions of oral Chinese patent medicines containing toxic decoction pieces issued by the outpatient and emergency department of Hohhot Mongolian Medicine of Traditional Chinese Medicine Hospital from January 1,2018 to May 31,2023 were extracted.Chinese Pharmacopoeia(2020 Edition)was used to classify the classification of toxic decoction pieces,and unreasonable usage was analyzed.Results A total of 15 083 prescriptions of Chinese patent medicines containing toxic decoction pieces were extracted,and 15 760 cases were used,including 24 kinds of Chinese patent medicines containing toxic decoction pieces.813 cases were used unreasonably,accounting for 5.16%,of which 642 cases were used excessively,accounting for 78.97%of the irrational cases.There were 217 cases of Chinese patent medicines of TCM decoction pieces containing heavy toxin,including 214 cases of excessive use,accounting for 98.62%.Unreasonable applications mainly focused on orthopedics,thyroid diseases,rheumatism and emergency medicine.Conclusion The excessive use of Chinese patent medicines containing toxic decoction pieces in our hospital is prominent,with potential safety hazards.Clinical pharmacists should start from prescription reviews,provide feedback to physicians,and explore the monitoring of rational medication.They should intervene in drug prescriptions that have obvious toxicity or are prone to adverse reactions,discuss corresponding standardized measures,in order to use drugs reasonably and avoid artificially controlled adverse reactions or poisoning situations.