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 explore the clinical and genetic characteristics of a fetus diagnosed with Congenital myasthenic syndrome type 16 (CMS16).Methods:A couple who had visited Tianjin Medical University General Hospital in February 2018 due to "adverse outcome of two pregnancies" was selected as the study subject. Clinical data was gathered. Peripheral blood and amniotic fluid samples were collected and subjected to whole exome sequencing (WES). Candidate variant was verified by Sanger sequencing. Low-depth whole-genome sequencing was carried out to detect copy number variation (CNV) in the fetus.Results:The couple′s first pregnancy had resulted in a miscarriage at 27 + 5 weeks, when ultrasound had revealed pleural effusion and polyhydramnios in the fetus. Their second pregnancy was terminated at 30 + 5 weeks due to fetal hand malformations, polyhydramnios and pleural fluid. Both couple had denied family history of genetic conditions. For their third pregnancy, no CNV abnormality was detected, whilst a compound heterozygous variants, including a maternally derived c. 3172C>T (p.R1058W) and paternal c. 1431delG (p.K477fs*89) in the SCN4A gene were detected. Based on the guidelines from the American College of Medical Genetics and Genomics, the c. 3172C>T (p.R1058W) was predicted as a likely pathogenic variant (PM1+ PM2_supporting+ PP3+ PP4), whilst the c. 1431delG (p.K477fs*89) was predicted as a pathogenic variant (PVS1+ PM2_supporting+ PP4). Conclusion:The c. 3172C>T (p.R1058W) and c. 1431delG (p.K477fs*89) compound heterozygous variants of the SCN4A gene probably underlay the CMS16 in the third fetus.

Objective:To explore the clinical and molecular basis for a Chinese pedigree affected with Complete androgen insensitivity syndrome (CAIS).Methods:A CAIS pedigree presented at Tianjin Medical University General Hospital between 2019 and 2021 was selected as the study subject. Clinical data of the proband was collected, along with peripheral blood samples from the proband and her family members. Chromosomal karyotyping, sex-determining region of the Y chromosome ( SRY) testing, and next-generation sequencing (NGS) were carried out for the proband, and candidate variant was verified by Sanger sequencing of her family members. Prenatal diagnosis was provided for the sister of the proband. This study was approved by Medical Ethics Committee of the Tianjin Medical University General Hospital (Ethics No. IRB2023-WZ-070). Results:The 18-year-old proband, who has a social gender of female, underwent laparoscopic examination, which showed no presence of uterus and ovaries. The karyotype of peripheral blood sample was 46, XY, with SRY gene detected. NGS indicated that the proband has harbored a heterozygous c. 1988C>G (p.Ser663Ter) variant of the AR gene. Sanger sequencing confirmed that her mother and sister had both harbored the same variant, whilst her father and younger sister were of the wild-type. Prenatal diagnosis revealed that her sister′s first fetus had harbored carried the same variant, which had led to termination of pregnancy. Her second fetus did not carry the variant, and a healthy boy was born. Based on guidelines from the American College of Medical Genetics and Genomics (ACMG), the variant was classified as likely pathogenic (PM2_Supporting+ PM4+ PP3_Moderate+ PP4). Conclusion:The c. 1988C>G (p.Ser663Ter) variant of the AR gene probably underlay the CAIS in the proband. The accurate diagnosis of sex development disorders will rely on the physicians′ thorough understanding of the clinical symptoms and pathogenic genes. Genetic testing and counseling can enable precise diagnosis, prenatal diagnosis, and guidance for reproduction

Objective·To establish various in vitro screening systems for the discovery of peptide inhibitors targeting the interaction between small ubiquitin-like modifier(SUMO)-activating enzyme subunit 1(SAE1)and subunit 2(SAE2),as well as to evaluate their advantages,disadvantages,and applicability to this research.Methods·The DNA fragments encoding human SAE1 and SAE2 were cloned into vector pET-28a,respectively,to generate protein SAE1 and SAE2.Purified proteins were used to establish screening assays,including isothermal calorimetry(ITC),fluorescence polarization(FP),surface plasmon resonance(SPR)and a fluorescence assay based on the SAE enzyme activity.The inhibitory activity of peptide candidates in different screening systems was examined,and their performance in terms of sensitivity,robustness,throughput and cost was evaluated.Results·The dissociation constant(Kd)of in vitro SAE1 and SAE2 interaction was determined to be 0.96 μmol/L by ITC,and PEPT7 was identified as the most potent peptide.However,the tracer of FP,which was derived from PEPT7,was not up to snuff due to its low affinity with SAE2.In the SPR assay,the Kd value(=1.13 μmol/L)of SAE1 and SAE2 interaction was in line with the results from ITC.The SAE enzyme activity-based screening assay revealed that HP1B,the most effective peptide,inhibited SAE with an half-maximal inhibitory concentration(IC50)of 15.72 μmol/L.The affinity of HP1B for SAE1 was determined to be 34.4 μmol/L by SPR.Conclusion·Several common screening systems for protein-protein interation(PPI)inhibitors are established and compared.Among them,ITC does not allow for high-throughput screening and it is difficult to accurately evaluate the low-affinity polypeptides with insignificant binding heat.The feasibility of FP relies heavily on the strong affinity between a tracer peptide and the protein target,making it unsuitable for the screening and optimization of low-affinity peptides.SPR is highly sensitive but the cost is high.The SAE enzyme activity-based assay stands out because it is a combination of high sensitivity,robustness,throughput and acceptable cost.

Objective:To study the epidemic characteristics of scrub typhus in Yantai City from 2006 to 2022, and provide a scientific basis for prevention and control of scrub typhus in Yantai City.Methods:In the subsystem "Infectious Disease Monitoring System" of the "China Disease Prevention and Control Information System", data on the outbreak of scrub typhus in Yantai City from January 1, 2006 to December 31, 2022 were collected and processed using software such as SPSS 23.0 for descriptive statistics.Results:A total of 599 scrub typhus cases were reported in Yantai City from 2006 to 2022, with an average annual reported incidence of 0.51/100 000. The reported incidence showed an upward trend year by year from 2006 to 2014 (χ 2trend = 144.72, P < 0.001), and reached a peak in 2014 (1.04/100 000). There was another small peak in 2019 (0.91/100 000). The incidence of scrub typhus showed a clear seasonal unimodal distribution, with October being the peak, accounting for 72.62% (435/599). In addition to Changdao County, other 12 cities (districts) reported scrub typhus cases. The top 3 cities with average annual reported incidence were Zhaoyuan City (1.58/100 000), Laizhou City (1.47/100 000) and Laiyang City (0.75/100 000). In all reported cases, the male to female ratio was 1.00∶1.07 (289∶310). The cases were mainly concentrated in the age range of 50 to 79, accounting for 74.46% (446/599). There was a statistically significant difference in the number of patients in different age groups in different years ( H = 38.71, P = 0.001). Farmers accounted for 88.65% (531/599) of the affected population. Conclusions:The incidence of scrub typhus in Yantai City shows an increasing trend and is widely distributed. It is recommended to strengthen the diagnosis, monitoring and infection management of scrub typhus.

Objective To explore a method to improve the accuracy and generalization ability of medical diagnostic neural network models under conditions of small data volumes,and to address the issue of poor neural network model performance in computer-aided diagnosis of nail diseases due to limited training data.Methods A dual-model strategy integrating instance segmentation with fine-grained feature classification was proposed.The neural network model based on dual-model strategy was trained using the dataset of Image-Based Intelligent Diagnosis of Nail Disease Model task of the first National Digital Health Innovation Application Competition & Health and Medical Big Data Theme Competition.This dataset covered 8 types of nail diseases,including nail matrix nevi,paronychia,nail psoriasis,onychomycosis,subungual hemorrhage,melanonychia,periungual warts,and nail melanoma,with class imbalance present.The diagnostic performance of the dual-model strategy was evaluated and compared with single-model strategies(image classification models[ResNet50 and Swin Transformer]and target detection model based on faster region-based convolutional neural network[Faster R-CNN])under the same hardware and software training conditions.Results The dataset included 1 048 samples,including 210 cases of nail matrix nevi,186 cases of paronychia,69 cases of nail psoriasis,203 cases of onychomycosis,149 cases of subungual hemorrhage,71 cases of melanonychia,93 cases of periungual warts,and 67 cases of nail melanoma,with 90％used for training various models and 10％for evaluation.The micro F1 score was 0.324 in the image classification model based on ResNet50,0.381 in the image classification model based on Swin Transformer,0.572 in the target detection model based on Faster R-CNN,and 0.714 in the dual-model strategy model Mask R-CNN+Swin Transformer.The accuracy rates for diagnosing different nail diseases in the dual-model strategy were:nail matrix nevi 80.95％(17/21),paronychia 89.47％(17/19),nail psoriasis 100.00％(7/7),onychomycosis 70.00％(14/20),subungual hemorrhage 73.33％(11/15),melanonychia 14.29％(1/7),periungual warts 55.56％(5/9),and nail melanoma 42.86％(3/7).The micro F1 score for evaluating the dual-model strategy on a test set of 1 000 cases was 0.844.Conclusion The dual-model strategy can effectively combine models with different functions to well accomplish the task of intelligent diagnosis of nail diseases under small data volume training conditions.

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.