Bladder cancer is one of the most prevalent cancers worldwide, with a high rate of recurrence and mortality, which is the ninth most common malignancy globally. Cystoscopy remains the gold standard for clinical bladder cancer diagnosis, but its invasive nature can lead to bacterial infection and inflammation. Urine cytology is a non-invasive and simple diagnostic method, but it has lower sensitivity in detecting low-grade bladder cancer and may yield false negative results. Therefore, identifying ideal diagnostic and prognostic biomarkers is crucial for accurate diagnosis and effective treatment of bladder cancer. Aptamers, characterized as single-stranded DNA or RNA with unique three-dimensional conformations, exhibit the ability to identify various targets, ranging from small molecules to tumor cells. Aptamers, also known as chemical antibodies, are generated by systematic evolution of ligands by exponential enrichment (SELEX) process and can function similarly to traditional antibodies. They hold numerous advantages over antibodies, such as ease of modification, low immunogenicity, and rapid tissue penetration and cell internalization due to their nucleic acid molecule structure. Since their discovery in the 1990s, aptamers have been widely used in biochemical analysis, disease detection, new drug research and other fields. This article provides an overview of aptamer selection and characterization for bladder cancer, discussing the research advancements involving aptamers in diagnosing and treating this disease. It covers aptamers obtained through different SELEX methods, including protein-SELEX, cell-SELEX, tissue-SELEX, and aptamers from other cancer SELEX; the detection in blood samples and urine samples; and application in targeted therapy and immunotherapy for bladder cancer. Currently, several aptamers capable of identifying bladder cancer have been generated, serving as molecular probes that have played a pivotal role in the early detection and treatment of bladder cancer. Bladder cancer perfusion therapy is well-suited for aptamer drug therapy because it does not require internal circulation, making it a suitable clinical indication for aptamer drug development. In addition, bladder cancer can be detected and monitored by collecting urine samples from patients, making it a preferred disease for clinical conversion of aptamers. While aptamers show promise, there is still much room for development compared with antibodies. There are still many clinically applied cancer biomarkers without corresponding aptamers, and more aptamers targeting different biomarkers should be selected and optimized to improve the sensitivity and accuracy for cancer detection and therapy. The field of aptamers urgently needs successful commercial products to promote its development, and home rapid detection/monitoring, imaging and targeted therapy of bladder cancer by infusion may be the breakthrough point for future application of aptamers.

Objective To investigate the effect and mechanism of proteasome inhibitor MG132 on memory impairment induced by chronic hypoxia in mice.Methods(1)A hypoxic model of the mouse midbrain dopaminergic neuron cell line MN9D was established using a hypoxia workstation.To observe the effects of hypoxia on the expression of TH,Ub-K48 and Ub-K63,MN9D cells were divided into normoxia group and hypoxia(12 h,24 h and 48 h)groups.To observe the effects of MG132 on the expression of the above-mentioned proteins,MN9D cells were divided into normoxia group,hypoxia group and hypoxia + MG132(25,50,100,200 μmol/L)group.(2)A mouse model of memory impairment was established using a hypobaric chamber.To observe the effects of hypobaric hypoxia on the expression of TH,Ub-K48 and Ub-K63 in the substantia nigra compacta(SNc)of mice,thirty C57BL/6 mice were randomly and equally divided into normoxia group and hypobaric hypoxia(3 d and 21 d)groups,10 in each group.To observe the effects of MG132 on spatial memory impairment induced by hypobaric hypoxia,twenty-four C57BL/6 mice were randomly and equally divided into normoxia group,hypobaric hypoxia 21 d group and hypobaric hypoxia 21 d+MG132 group,8 in each group.(3)The protein expression levels of TH,Ub-K48,and Ub-K63 in MN9D cells which were either subjected to different durations of hypoxia treatment or pre-treated with MG132 prior to hypoxia treatment were detected using Western blotting(WB).The novel object recognition test was used to detect the memory function of mice.Immunofluorescence was used to detect the proportion of positive immunoreactive area of TH response in the SNc region.The expression levels of TH,Ub-K48,and Ub-K63 in the SNc region were detected by WB.Results(1)Compared with normoxia group,MN9D cells in hypoxia 24 h group showed increasing expression of Ub-K48 and Ub-K63(P<0.05),and decreasing expression of TH(P<0.05),and MN9D cells in all hypoxia groups showed increasing expression of Ub-K48/TH and Ub-K63/TH(P<0.05).Compared with hypoxia group,MN9D cells showed decreasing expression of Ub-K48/TH and Ub-K63/TH in hypoxia + MG132 100 umol/L group and hypoxia + MG132 200 umol/L group(P<0.05).(2)Compared with the mice in normoxia group,mice in 3 d and 21 d hypobaric hypoxia groups showed decreasing expression of TH(P<0.001),and increasing expression of Ub-K48/TH and Ub-K63/TH(P<0.05)in the SNc region.Compared with normoxia group,the mice in 21 d hypobaric hypoxia group showed a lower new object recognition index(P<0.01),and the proportion of positive immunoreactive area of TH response in the SNc region(P<0.05).Compared with 21 d hypobaric hypoxia group,the mice in hypobaric hypoxia 21 d+MG132 group showed a higher new object recognition index(P<0.01).Conclusion The proteasome inhibitor MG132 could alleviate the memory impairment induced by chronic hypoxia in mice,and its mechanism may be related to the inhibition of Ub-K63 and Ub-K48,which in turn upregulates expression of TH in dopaminergic neurons.

Objective: To investigate the poisonous substances and geographical distribution of poisoning in children in China. Methods: A cross-sectional study. The clinical data of 8 385 hospitalized children from January 2016 to December 2020 were extracted from the FUTang Updating Medical Records database. These children aged 0 to 18 years and were admitted due to poisoning. They were grouped according to age (newborns and infants, toddlers, preschoolers, school-age children, adolescents), place of residence (Northeast China, North China, Central China, East China, South China, Southwest China, Northwest China), and mode of discharge (discharge under medical advice, transfer to another hospital under medical advice, discharge without medical advice, death, other). The poisonous substance and causes of poisoning in different groups were analyzed. Results: Among these 8 385 children, 4 734 (56.5%) were male and 3 651 (43.5%) female, with a male-to-female ratio of 1.3∶1. The age was 3 (2, 7) years. The prevalence of poisoning was 51.8% (4 343/8 385) in toddlers, 16.5% (1 380/8 385) in adolescents, 14.8% (1 242/8 385) in preschoolers, 14.4% (1 206/8 385) in school-age children, and 2.5% (214/8 385) in newborns and infants. Drug poisoning accounted for 43.5% (3 649/8 385) and pesticide accounted for 26.8% (2 249/8 385). Drug poisoning was more common in adolescents (684/1 380, 49.6%) and toddlers (2 041/4 343, 47.0%); non-drug poisoning was more common in school-age children (891/1 206, 73.9%), of which carbon monoxide was mainly in newborns and infants (41/214, 19.2%) and food poisoning in children of school age (241/1 206, 20.0%). Regarding regional characteristics, drug poisoning was more frequent in South China (188/246, 64.2%) and non-drug poisoning was more frequent in Southwest China (815/1 123, 72.5%). For drugs, anti-epileptic drugs, sedative-hypnotic drugs and anti-Parkinson's disease drugs had a higher proportion of poisoning in North China (138/1 034, 13.0%) than that in other regions. For non-drug poisoning, pesticides (375/1 123, 33.3%), food poisoning (209/1 123, 18.6%) and contact with poisonous animals (86/1 123, 7.7%) were more common in Southwest China than in other regions; carbon monoxide poisoning was more common in North China (81/1 034, 7.6%) and Northwest China (65/1 064, 6.3%). In Central China, poisoning happened more in toddlers (792/1 295, 61.2%) and less in adolescents (115/1 295, 8.8%) than in other regions. Regarding different age groups, poisoning in adolescent happened more in Northeast China (121/457, 26.5%), North China (240/1 034, 23.2%), and Northwest China (245/1 064, 23.0%). The rate of discharge under medical advice, discharge without medical advice, and mortality rate within the 5 years were 77.0% (6 458/8 385), 20.8% (1 743/8 385), 0.5% (40/8 385), respectively. Conclusions: Poisoning is more common in male and toddlers. Poisonous substances show a regional characteristic and vary in different age groups, with drugs and insecticides as the most common substances.
Infant ; Adolescent ; Animals ; Child ; Male ; Humans ; Infant, Newborn ; Female ; Child, Hospitalized ; Cross-Sectional Studies ; Carbon Monoxide Poisoning/epidemiology* ; Pesticides ; Foodborne Diseases ; Hospitals ; Drug-Related Side Effects and Adverse Reactions ; China/epidemiology*

Objective: To explore the risk intensity and related influencing factors of post-traumatic stress disorder (PTSD) among high-stress rescue workers, and to provide effective tools for the risk assessment of PTSD in military rescue workers. Method: From June to August 2022, cluster sampling was used to select the high-stress rescue personnel of an Army department as the survey subjects. The acute Stress reaction (ASD) scale and PTSD checklist were used to evaluate the risk of PTSD in military rescue personnel. Multivariate logistic regression were used to analyze the influencing factors of PTSD. Results: The age of 4 460 subjects was (24.38±4.072) years old, including 4 396 males (98.6%). The positive rate of initial screening for ASD was 2.85% (127/4 460). The positive rate of PTSD was 0.67% (30/4 460). Multivariate logistic regression model analysis showed that female, older age, recent trauma exposure history, passive smoking and alcohol consumption were at higher risk of ASD, the values of OR (95%CI) were 4.183 (1.819-9.618), 6.278 (1.363-28.912), 3.094 (1.500-6.379), 2.059 (1.298-3.267) and 2.607 (1.614-4.211), respectively; Lower education level was associated with lower risk of ASD, OR (95%CI) was 0.593 (0.359-0.978); People who are older, thinner, have a history of mental illness, and drink alcohol were at higher risk for PTSD, the values of OR (95%CI) were 20.144 (2.459-165.043), 10.287 (2.218-47.700), 91.104 (8.592-965.980) and 2.866 (1.144-7.180), respectively. Conclusion: Gender, age, education level, passive smoking, alcohol consumption, past history of mental illness and body mass index may be related to the potential risk of PTSD in rescue workers,passive smoking, alcohol consumption, and weight controlling should be focused on to reduce potential risks of PTSD.
Male ; Humans ; Female ; Young Adult ; Adult ; Stress Disorders, Post-Traumatic/prevention & control* ; Tobacco Smoke Pollution ; Risk Assessment ; Military Personnel ; Alcohol Drinking

Emodin nanostructured lipid carriers(ED-NLC) were prepared and their quality was evaluated in vitro. Based on the results of single-factor experiments, the ED-NLC formulation was optimized by Box-Behnken response surface method with the dosages of emodin, isopropyl myristate and poloxamer 188 as factors and the nanoparticle size, encapsulation efficiency and drug loading as evaluation indexes. Then the evaluation was performed on the morphology, size and in vitro release of the nanoparticles prepared by emulsification-ultrasonic dispersion method in line with the optimal formulation, i.e., 3.27 mg emodin, 148.68 mg isopropyl myristate and 173.48 mg poloxamer 188. Under a transmission electron microscope(TEM), ED-NLC were spherical and their particle size distribution was uniform. The particle size of ED-NLC was(97.02±1.55) nm, the polymer dispersion index 0.21±0.01, the zeta potential(-38.96±0.65) mV, the encapsulation efficiency 90.41%±0.56% and the drug loading 1.55%±0.01%. The results of differential scanning calorimeter(DSC) indicated that emodin may be encapsulated into the nanostructured lipid carriers in molecular or amorphous form. In vitro drug release had obvious characteristics of slow release, which accorded with the first-order drug release equation. The fitting model of Box-Behnken response surface methodology was proved accurate and reliable. The optimal formulation-based ED-NLC featured concentrated particle size distribution and high encapsulation efficiency, which laid a foundation for the follow-up study of ED-NLC in vivo.
Drug Carriers ; Emodin ; Follow-Up Studies ; Lipids ; Nanostructures

Tenuifolin， a main component in Polygalae Radix， is frequently used as an important indicator for quality control of Polygalae Radix and its processed products. Dementia is a serious and persistent cognitive disorder， and the number of dementia patients is increasing worldwide， which brings great economic burden and mental pressure to families and society. At present， cholinesterase inhibitor and other drugs can only alleviate the symptoms of dementia， and there are some toxic and side effects. It has been found that tenuifolin can significantly improve cognitive disorder， learning and memory and is expected to be a potential drug for treating dementia. Tenuifolin exerts protective effects on amyloid-β （Aβ） deposition， acetylcholine reduction， neuroinflammation， cellular oxidative damage and nerve cell apoptosis caused by neurodegenerative diseases via multiple mechanisms， and can be applied to various types of dementia. In addition， it can be quickly absorbed into the blood， mainly distributed in liver and kidney， and can enter into the brain through the blood-brain barrier. However， because of its large molecular mass and poor fat solubility， tenuifolin can be rapidly eliminated， generating some problems such as low oral absoBrbability and permeability of blood-brain barrier. Therefore， the information of chemistry， pharmacology， pharmacokinetics and toxicology of tenuifolin was summarized in this paper to provide reference and ideas for further research and application.

Objective: Bioinformatics methods were used to mine differentially expressed genes (DEGs) and enriched signal pathways induced by chronic pesticide exposure, and explore its potential pathogenic mechanisms and key genes. Methods: In July 2021, high-throughput gene expression profile data related to pesticide toxicity was downloaded from Gene Expression Omnibus (GEO) database to obtain DEGs. The samples were from American male farm workers who had been exposed to pesticides for a long time and other industry workers. The functional enrichment analysis of GO, KEGG and Geme Set Enrichment Analysis (GSEA) were performed by R package clusterProfiler. STRING, Cytoscape and other tools were applied to construct and visualize the protein interaction network. With the help of MCODE and Cytohubba plugins, gene function modules were obtained, and hub gene was screened out. Results: 189 DEGs were screened from GSE30335 dataset, including 101 up-regulated genes and 88 down-regulated genes. The results of GO, KEGG and GSEA were mainly enriched in biological functions such as regulation of neuron projection development, regulation of locomotion, ribosomal protein synthesis, and pathways related to complex nervous system diseases such as Parkinson's disease. And the comprehensive screening showed that KLF1 was the hub gene of pesticide exposure, with a fold change of 0.456 (t=-3.82, P=0.021) . Conclusion: Long term exposure to pesticides results in the differential expression of multiple genes in the exposed population, which may be involved in the pathological changes of nervous system by down regulating KLF1 and related biological pathways.
Computational Biology/methods* ; Gene Expression Profiling/methods* ; Gene Regulatory Networks ; Genetic Association Studies ; Humans ; Male ; Pesticides/toxicity*

Objective: To explore the pathological characteristics of three mice models of temporomandibular joint degenerative joint disease (TMJDJD), including osteoarthritis and osteoarthrosis, and to provide references for animal experimental study regarding the pathological mechanism of osteoarthritis and osteoarthrosis. Methods: A total of 54 8-week-old male C57BL/6 mice were selected to construct three TMJDJD animal models, including bilateral temporomandibular joint (TMJ) Freund's complete adjuvant (FCA) injection model, bilateral TMJ monosodium iodoacetate (MIA) injection model, and right TMJ discectomy model. FCA injection model (15 mice) was divided into saline injection group, FCA injection group-1 week, FCA injection group-2 week, FCA injection group-4 week and FCA injection group-6 week, 3 mice were used at each time point, with a total of 6 TMJs on both sides. MIA injection model (15 mice) was separated into saline injection group, MIA injection group-1 week, MIA injection group-2 week, MIA injection group-4 week and MIA injection group-6 week, 3 mice were used at each time point, with a total of 6 TMJs on both sides. TMJ discectomy model (24 mice) was split into control group, discectomy group-2 week group, discectomy group-4 week and discectomy group-6 week, six mice were used at each time point, with a total of six right TMJs. General pictures of the bilateral joints area of mice were collected 1 day after drug injection, and stereoscopic images of condylar tissues were collected 4 weeks after microsurgery for discectomy. Mouse TMJ tissue sections from each time point were stained with HE and toluidine blue, respectively, synovial tissues were scored for synovial inflammation, and the percentage of proteoglycan in condylar cartilage was quantitatively analyzed. Results: One day after intra-articular FCA or MIA injection, the width of bilateral TMJ were significantly increased in FCA injection groups [(24.60±0.46) mm] compared with the saline injection group [(21.63±0.52) mm] (t=4.25, P<0.013), the width of bilateral TMJ in MIA injection groups [(24.50±0.62) mm] were also significantly higher than that in saline injection group [(21.40±0.52) mm] (t=3.82, P=0.019). The synovitis scores in FCA injection groups 1, 2, 4, 6 weeks after FCA injection were significantly higher than that of the saline injection group (F=18.09, P<0.001), with the proteoglycan of condylar cartilage increased firstly and then decreased compared with the saline injection group (F=21.59, P<0.001). Condylar cartilage proteoglycan loss in different degrees were observed 1, 2, 4 and 6 weeks after MIA injection (F=13.59, P<0.001), and synovitis scores were increased at different degrees compared with saline injection group (F=14.79, P<0.001). The morphology of condylar cartilage in discectomy groups mice were severely damaged, synovial tissues showed dense connective tissue lesions at 2, 4 and 6 weeks postoperatively, condylar cartilage tissues showed a time-dependent loss of proteoglycan compared with the control group (F=40.62, P<0.001). Conclusions: Intra-articular FCA injection establishes a mouse model of TMJ osteoarthritis with severe synovial inflammation. Intra-articular MIA injection constructs a mouse model of typical TMJ osteoarthritis. Discectomy establishes a mouse TMJ osteoarthrosis model with severe condylar cartilage destruction.
Mice ; Male ; Animals ; Cartilage, Articular ; Osteoarthritis/pathology* ; Iodoacetic Acid ; Tolonium Chloride ; Mice, Inbred C57BL ; Temporomandibular Joint/pathology* ; Disease Models, Animal ; Proteoglycans ; Synovitis/pathology* ; Inflammation/pathology*

Arthroplasty, Replacement, Hip ; Female ; Femoral Neck Fractures/surgery* ; Humans ; Osteoporosis/surgery* ; Pregnancy

Based on the needs of healthcare system reform, Australia has implemented activity based funding(ABF) payment mode nationwide, and established the Independent Hospital Pricing Authority as the specific implementation agency in 2011. The main responsibilities and functions of the ABF payment mode covers pricing of medical services, classification of healthcare services, collection of clinical data and cost accounting of healthcare services. ABF payment mode presents outstanding advantages in promoting the capacity of healthcare service, maintaining fairness of healthcare service supplies and carrying out cooperation across different institutions. These efforts provide important references for China in its top-level design of payment method, pilot project of classification system, medical service items and price dynamic adjustment, informationization and information standardization construction among public hospitals.