RNA fluorescence aptamers are RNA sequences that can specifically bind to non-toxic,cell permeable,and self-fluorescent target molecules and activate their luminescent properties.These aptamers provide powerful tools for biosensing and imaging researches due to their simple structure,easy synthesis,and easy transfection.This article summarized the characteristics and development history of various RNA fluorescent aptamers,including Malachite Green,Spinach,Broccoli,Mango,Corn,and Pepper family,as well as their corresponding fluorescent groups.The applications of RNA fluorescent aptamers were also reviewed from two aspects:extracellular detection and cell imaging.This review might provide guidance for labeling,detection and interactions of molecules from proof of concept and clinical assessment to practical clinical and biomedical applications.

Objective To analyze the molecular markers of various nuclei in the human basal ganglia and the differentially expressed genes(DEGs)among different nuclei,gender,and Parkinson's disease(PD),followed by the biological function annotations of the DEGs.Methods Forty-five specimens of basal ganglia from 10 human postmortem brains were divided into control and PD groups,and the control group was further categorized into female and male groups.RNA from each sample was extracted for high-throughput transcriptome sequencing.Bioinformatic analysis was conducted to identify molecular markers of each nuclei in the control group,nuclei-specific,gender-specific,and PD-specific DEGs,followed by gene enrichment analysis and functional annotation.Results Sequencing analysis revealed top DEGs such as DRD1,FOXG1,and FAM183A in the caudate;SLC6A3,EN1,SLC18A2,and TH in the substantia nigra;MEPE and FGF10 in the globus pallidus;and SLC17A6,PMCH,and SHOX2 in the subthalamic nucleus.In them,putamen showed some overlapping DEGs with caudate,such as DRD1 and FOXG1.A significant number of DEGs were identified among different nuclei in the control group,with the highest number between caudate and globus pallidus(9321),followed by putamen and globus pallidus(6341),caudate and substantia nigra(6054),and substantia nigra and subthalamic nucleus(44).Gene enrichment analysis showed that downregulated DEGs between caudate and globus pallidus were significantly enriched in processes like myelination of neurons and cell migration.Upregulated DEGs between putamen and globus pallidus were enriched processes like chemical synaptic transmission and regulation of membrane potential,while downregulated DEGs were enriched in myelination and cell adhesion.Upregulated DEGs between caudate and substantia nigra were enriched in processes like chemical synaptic transmission and axonal conduction,while downregulated DEGs were enriched in myelination of neurons.Totally 468,548,1402,333,and 341 gender-specific upregulated DEGs and 756,988,2532,444,and 1372 downregulated DEGs were identified in caudate,putamen,substantia nigra,globus pallidus,and subthalamus nucleus.Gene enrichment analysis revealed upregulated DEGs mostly enriched in pathways related to immune response and downregulated DEGs in chemical synaptic transmission.At last,709,852,276,507,and 416 PD-specific upregulated DEGs and 830,2014,1218,836,and 1730 downregulated DEGs were identified in caudate,putamen,substantia nigra,globus pallidus,and subthalamus nucleus.Gene enrichment analysis revealed upregulated DEGs mostly enriched in apoptotic regulation and downregulated DEGs in chemical synaptic transmission and action potential regulation.Conclusion We identified and analysed the molecular markers of different human basal ganglia nuclei,as well as DEGs among different nuclei,different gender,and between control and PD.

OBJECTIVE: To evaluate the prospective association between cumulative resting heart rate (cumRHR) and rapid renal function decline (RRFD) in a cohort of individuals aged 60 and older. METHODS: In the Tianjin Chronic Kidney Disease Cohort Study, the individuals who underwent three consecutive physical examinations between 2014 and 2017, with estimated glomerular filtration rate (eGFR) greater than 60 mL/min per 1.73 m² and aged 60 years or older were enrolled. A total of 27,564 patients were prospectively followed up from January 1, 2017 to December 31, 2020. The 3-year cumRHR was calculated. The primary outcome was RRFD, defined as an annualized decline in eGFR of 5 mL/min per 1.73 m² or greater. Logistic and restricted spline regression models and subgroup analysis were used to investigate the association of cumRHR with RRFD after adjusting for all confounders. RESULTS: During a median follow-up of 3.2 years, a total of 4,347 (15.77%) subjects developed RRFD. In fully-adjusted models, compared with the lowest quartile of cumRHR, the odds ratio (OR) for the highest was 1.44 (1.28-1.61), P < 0.001. Furthermore, each 1-standard deviation (27.97 beats/min per year) increment in cumRHR was associated with a 17% (P < 0.001) increased risk of RRFD, with a linear positive correlation (P for non-linear = 0.803). Participants with a 3-year cumRHR ≥ 207 (beats/min) * year (equivalent to ≥ 69 beats/min per year in 3 years) were found to be at a higher risk of RRFD. CONCLUSIONS The cumRHR is significantly associated with a higher risk of RRFD among older adults. These results might provide an effective goal for managing and delaying the decline of renal function in the older adults.

Deficiencies in the clearance of peripheral amyloid β (Aβ) play a crucial role in the progression of Alzheimer's disease (AD). Previous studies have shown that the ability of blood monocytes to phagocytose Aβ is decreased in AD. However, the exact mechanism of Aβ clearance dysfunction in AD monocytes remains unclear. In the present study, we found that blood monocytes in AD mice exhibited decreases in energy metabolism, which was accompanied by cellular senescence, a senescence-associated secretory phenotype, and dysfunctional phagocytosis of Aβ. Improving energy metabolism rejuvenated monocytes and enhanced their ability to phagocytose Aβ in vivo and in vitro. Moreover, enhancing blood monocyte Aβ phagocytosis by improving energy metabolism alleviated brain Aβ deposition and neuroinflammation and eventually improved cognitive function in AD mice. This study reveals a new mechanism of impaired Aβ phagocytosis in monocytes and provides evidence that restoring their energy metabolism may be a novel therapeutic strategy for AD.
Animals ; Mice ; Alzheimer Disease ; Amyloid beta-Peptides ; Monocytes ; Cognition ; Energy Metabolism ; Phagocytosis

Objective: The kidney disease: improving global outcome (KDIGO) and pediatric reference change value optimized for acute kidney injury (pROCK) criteria were used to evaluate the incidence, stages and mortality of acute kidney injury (AKI). The differences between the 2 criteria were compared for exploring the value of pROCK criteria in diagnosing pediatric AKI and predicting adverse outcomes. Methods: In the multicenter prospective clinical cohort study, we collected general data and clinical data such as serum creatinine values from 1 120 children admitted to 4 PICUs of Children's Hospital of Soochow University, Children's Hospital of Fudan University, Anhui Provincial Children's Hospital, and Xuzhou Children's Hospital from September 2019 to February 2021. AKI was defined and staged according to the KDIGO and pROCK criteria. The incidence of AKI, the consistency of AKI definite diagnosis and stages, and the mortality in PICU were compared between the 2 groups. The chi-square test or Fisher's exact test was applied for comparison between 2 groups. The Cohen's Kappa and Weighted Kappa analyses were used for evaluating diagnostic consistency. The Cox regression analysis was used to evaluate the correlation between AKI and mortality. Results: A total of 1 120 critically ill children were included, with an age of 33 (10, 84) months. There are 668 boys and 452 girls. The incidence of AKI defined by the KDIGO guideline was higher than that defined by pROCK criteria (27.2%(305/1 120), 14.7%(165/1 120), χ²=52.78, P<0.001). The concordance rates of the 2 criteria for the diagnosis of AKI and AKI staging were 87.0% (κ=0.62) and 79.7% (κ=0.58), respectively. Totally 63 infants with AKI stage 1 defined by the KDIGO guideline were redefined as non-AKI by following the pROCK criteria. The PICU mortality rate of these infants was similar to patients without AKI defined by KDIGO guideline(P=0.761). After adjusting for confounders, AKI defined by KDIGO or pROCK criteria was an independent risk factor of death in PICU (AHR=2.04, 2.73,95%CI 1.27-3.29, 1.74-4.28, both P<0.01), and the risk of death was higher when using the pROCK compared with the KDIGO criteria. As for the KDIGO criteria, mild AKI was not associated with the mortality in PICU (P=0.702), while severe AKI was associated with increased mortality (P<0.001). As for the pROCK criteria, both mild and severe AKI were risk factors of PICU death in children (HR=3.51, 6.70, 95%CI 1.94-6.34, 4.30-10.44, both P<0.001). In addition, The AKI severity was positively associated with the mortality. Conclusions: The AKI incidence and staging varied depending on the used diagnostic criteria. The KDIGO definition is more sensitive, while the pROCK-defined AKI is more strongly associated with high mortality rate.
Child ; Child, Preschool ; Female ; Humans ; Infant ; Male ; Acute Kidney Injury/epidemiology* ; Cohort Studies ; Critical Illness ; Prospective Studies ; Risk Factors

During coronavirus disease 2019 epidemic, the treatment of severe trauma has been impacted. The Consensus on emergency surgery and infection prevention and control for severe trauma patients with 2019 novel corona virus pneumonia was published online on February 12, 2020, providing a strong guidance for the emergency treatment of severe trauma and the self-protection of medical staffs in the early stage of the epidemic. With the Joint Prevention and Control Mechanism of the State Council renaming "novel coronavirus pneumonia" to "novel coronavirus infection" and the infection being managed with measures against class B infectious diseases since January 8, 2023, the consensus published in 2020 is no longer applicable to the emergency treatment of severe trauma in the new stage of epidemic prevention and control. In this context, led by the Chinese Traumatology Association, Chinese Trauma Surgeon Association, Trauma Medicine Branch of Chinese International Exchange and Promotive Association for Medical and Health Care, and Editorial Board of Chinese Journal of Traumatology, the Chinese expert consensus on emergency surgery for severe trauma and infection prevention during coronavirus disease 2019 epidemic ( version 2023) is formulated to ensure the effectiveness and safety in the treatment of severe trauma in the new stage. Based on the policy of the Joint Prevention and Control Mechanism of the State Council and by using evidence-based medical evidence as well as Delphi expert consultation and voting, 16 recommendations are put forward from the four aspects of the related definitions, infection prevention, preoperative assessment and preparation, emergency operation and postoperative management, hoping to provide a reference for severe trauma care in the new stage of the epidemic prevention and control.

Objective: To investigate the influence of extending the waiting time on tumor regression after neoadjuvant chemoradiology (nCRT) in patients with locally advanced rectal cancer (LARC). Methods: Clinicopathological data from 728 LARC patients who completed nCRT treatment at the First Affiliated Hospital, Naval Medical University from January 2012 to December 2021 were collected for retrospective analysis. The primary research endpoint was the sustained complete response (SCR). There were 498 males and 230 females, with an age (M(IQR)) of 58 (15) years (range: 22 to 89 years). Logistic regression models were used to explore whether waiting time was an independent factor affecting SCR. Curve fitting was used to represent the relationship between the cumulative occurrence rate of SCR and the waiting time. The patients were divided into a conventional waiting time group (4 to <12 weeks, n=581) and an extended waiting time group (12 to<20 weeks, n=147). Comparisons regarding tumor regression, organ preservation, and surgical conditions between the two groups were made using the t test, Wilcoxon rank sum test, or χ² test as appropriate. The Log-rank test was used to elucidate the survival discrepancies between the two groups. Results: The SCR rate of all patients was 21.6% (157/728). The waiting time was an independent influencing factor for SCR, with each additional day corresponding to an OR value of 1.010 (95%CI: 1.001 to 1.020, P=0.031). The cumulative rate of SCR occurrence gradually increased with the extension of waiting time, with the fastest increase between the 9^th to <10^th week. The SCR rate in the extended waiting time group was higher (27.9%(41/147) vs. 20.0%(116/581), χ²=3.901, P=0.048), and the organ preservation rate during the follow-up period was higher (21.1%(31/147) vs. 10.7%(62/581), χ²=10.510, P=0.001). The 3-year local recurrence/regrowth-free survival rates were 94.0% and 91.1%, the 3-year disease-free survival rates were 76.6% and 75.4%, and the 3-year overall survival rates were 95.6% and 92.2% for the conventional and extended waiting time groups, respectively, with no statistical differences in local recurrence/regrowth-free survival, disease-free survival and overall survival between the two groups (χ²=1.878, P=0.171; χ²=0.078, P=0.780; χ²=1.265, P=0.261). Conclusions: An extended waiting time is conducive to tumor regression, and extending the waiting time to 12 to <20 weeks after nCRT can improve the SCR rate and organ preservation rate, without increasing the difficulty of surgery or altering the oncological outcomes of patients.

With the development of artificial intelligence (AI) technology, it has a wide range of explorations in orthodontics. AI has greater application prospects in precise measurement, multidimensional diagnosis, treatment planning and efficacy prediction. At the same time, there are certain limitations in the application of AI, such as risks caused by individual variability, black box properties and unclear delineation of medical responsibilities. This paper summarized the history and current status of AI applications in orthodontics and discussed future development trends, to provide reference for clinical orthodontics.
Humans ; Artificial Intelligence ; Orthodontics ; Dental Care ; Forecasting ; Delivery of Health Care

Objective: To develop a multi-classification orthodontic image recognition system using the SqueezeNet deep learning model for automatic classification of orthodontic image data. Methods: A total of 35 000 clinical orthodontic images were collected in the Department of Orthodontics, Capital Medical University School of Stomatology, from October to November 2020 and June to July 2021. The images were from 490 orthodontic patients with a male-to-female ratio of 49∶51 and the age range of 4 to 45 years. After data cleaning based on inclusion and exclusion criteria, the final image dataset included 17 453 face images (frontal, smiling, 90° right, 90° left, 45° right, and 45° left), 8 026 intraoral images [frontal occlusion, right occlusion, left occlusion, upper occlusal view (original and flipped), lower occlusal view (original and flipped) and coverage of occlusal relationship], 4 115 X-ray images [lateral skull X-ray from the left side, lateral skull X-ray from the right side, frontal skull X-ray, cone-beam CT (CBCT), and wrist bone X-ray] and 684 other non-orthodontic images. A labeling team composed of orthodontic doctoral students, associate professors, and professors used image labeling tools to classify the orthodontic images into 20 categories, including 6 face image categories, 8 intraoral image categories, 5 X-ray image categories, and other images. The data for each label were randomly divided into training, validation, and testing sets in an 8∶1∶1 ratio using the random function in the Python programming language. The improved SqueezeNet deep learning model was used for training, and 13 000 natural images from the ImageNet open-source dataset were used as additional non-orthodontic images for algorithm optimization of anomaly data processing. A multi-classification orthodontic image recognition system based on deep learning models was constructed. The accuracy of the orthodontic image classification was evaluated using precision, recall, F1 score, and confusion matrix based on the prediction results of the test set. The reliability of the model's image classification judgment logic was verified using the gradient-weighted class activation mapping (Grad-CAM) method to generate heat maps. Results: After data cleaning and labeling, a total of 30 278 orthodontic images were included in the dataset. The test set classification results showed that the precision, recall, and F1 scores of most classification labels were 100%, with only 5 misclassified images out of 3 047, resulting in a system accuracy of 99.84%(3 042/3 047). The precision of anomaly data processing was 100% (10 500/10 500). The heat map showed that the judgment basis of the SqueezeNet deep learning model in the image classification process was basically consistent with that of humans. Conclusions: This study developed a multi-classification orthodontic image recognition system for automatic classification of 20 types of orthodontic images based on the improved SqueezeNet deep learning model. The system exhibitted good accuracy in orthodontic image classification.
Humans ; Male ; Female ; Child, Preschool ; Child ; Adolescent ; Young Adult ; Adult ; Middle Aged ; Deep Learning ; Reproducibility of Results ; Radiography ; Algorithms ; Cone-Beam Computed Tomography

Central sensitization is essential in maintaining chronic pain induced by chronic pancreatitis (CP), but cortical modulation of painful CP remains elusive. Here, we examined the role of the anterior cingulate cortex (ACC) in the pathogenesis of abdominal hyperalgesia in a rat model of CP induced by intraductal administration of trinitrobenzene sulfonic acid (TNBS). TNBS treatment resulted in long-term abdominal hyperalgesia and anxiety in rats. Morphological data indicated that painful CP induced a significant increase in FOS-expressing neurons in the nucleus tractus solitarii (NTS) and ACC, and some FOS-expressing neurons in the NTS projected to the ACC. In addition, a larger portion of ascending fibers from the NTS innervated pyramidal neurons, the neural subpopulation primarily expressing FOS under the condition of painful CP, rather than GABAergic neurons within the ACC. CP rats showed increased expression of vesicular glutamate transporter 1, and increased membrane trafficking and phosphorylation of the N-methyl-D-aspartate receptor (NMDAR) subunit NR2B and the α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor (AMPAR) subunit GluR1 within the ACC. Microinjection of NMDAR and AMPAR antagonists into the ACC to block excitatory synaptic transmission significantly attenuated abdominal hyperalgesia in CP rats, which was similar to the analgesic effect of endomorphins injected into the ACC. Specifically inhibiting the excitability of ACC pyramidal cells via chemogenetics reduced both hyperalgesia and comorbid anxiety, whereas activating these neurons via optogenetics failed to aggravate hyperalgesia and anxiety in CP rats. Taken together, these findings provide neurocircuit, biochemical, and behavioral evidence for involvement of the ACC in hyperalgesia and anxiety in CP rats, as well as novel insights into the cortical modulation of painful CP, and highlights the ACC as a potential target for neuromodulatory interventions in the treatment of painful CP.
Animals ; Anxiety/etiology* ; Chronic Pain/etiology* ; GABAergic Neurons ; Gyrus Cinguli/metabolism* ; Hyperalgesia/metabolism* ; Pancreatitis, Chronic/pathology* ; Rats ; Rats, Sprague-Dawley ; Receptors, N-Methyl-D-Aspartate/metabolism* ; Trinitrobenzenesulfonic Acid/toxicity*