The aging microenvironment, as a key driver of tumorigenesis and progression, plays a critical role in tumor immune regulation through one of its core features-the senescence-associated secretory phenotype (SASP). SASP consists of a variety of interleukins, chemokines, proteases, and growth factors. It initially induces surrounding cells to enter a state of senescence through paracrine mechanisms, thereby creating a sustained inflammatory stimulus and signal amplification effect within the tissue microenvironment. Furthermore, these secreted factors activate key signaling pathways such as NF-κB, cGAS-STING, and mTOR, which regulate the expression of immune-related molecules (such as PD-L1) and promote the recruitment of immunosuppressive cells, including regulatory T cells and myeloid-derived suppressor cells. This process ultimately contributes to the formation of an immunosuppressive tumor microenvironment. Furthermore, the article explores potential anti-tumor immunotherapy strategies targeting SASP and its associated molecular mechanisms, including approaches to inhibit SASP secretion or eliminate senescent cells. Although these strategies have shown promise in certain tumor models, the high heterogeneity among tumor types may result in varied responses to SASP-targeted therapies. This highlights the need for further research into adaptive stratification and personalized treatment approaches. Targeting immune regulatory mechanisms in the aging microenvironment-particularly SASP-holds great potential for advancing future anti-tumor therapies.

Anxiety disorder is a major symptom of autism spectrum disorder (ASD) with a comorbidity rate of ~40%. However, the neural mechanisms of the emergence of anxiety in ASD remain unclear. In our study, we found that hyperactivity of basolateral amygdala (BLA) pyramidal neurons (PNs) in Shank3 InsG3680 knock-in (InsG3680^+/+) mice is involved in the development of anxiety. Electrophysiological results also showed increased excitatory input and decreased inhibitory input in BLA PNs. Chemogenetic inhibition of the excitability of PNs in the BLA rescued the anxiety phenotype of InsG3680^+/+ mice. Further study found that the diminished control of the BLA by medial prefrontal cortex (mPFC) and optogenetic activation of the mPFC-BLA pathway also had a rescue effect, which increased the feedforward inhibition of the BLA. Taken together, our results suggest that hyperactivity of the BLA and alteration of the mPFC-BLA circuitry are involved in anxiety in InsG3680^+/+ mice.
Animals ; Prefrontal Cortex/metabolism* ; Basolateral Nuclear Complex/metabolism* ; Mice ; Anxiety/metabolism* ; Nerve Tissue Proteins/genetics* ; Male ; Gene Knock-In Techniques ; Pyramidal Cells/physiology* ; Mice, Transgenic ; Neural Pathways/physiopathology* ; Mice, Inbred C57BL ; Microfilament Proteins

Digital technologies have become an integral part of complete denture restoration. With advancement in computer-aided design and computer-aided manufacturing (CAD/CAM), tools such as intraoral scanning, facial scanning, 3D printing, and numerical control machining are reshaping the workflow of complete denture restoration. Unlike conventional methods that rely heavily on clinical experience and manual techniques, digital technologies offer greater precision, predictability, and efficacy. They also streamline the process by reducing the number of patient visits and improving overall comfort. Despite these improvements, the clinical application of digital complete denture restoration still faces challenges that require further standardization. The major issues include appropriate case selection, establishing consistent digital workflows, and evaluating long-term outcomes. To address these challenges and provide clinical guidance for practitioners, this expert consensus outlines the principles, advantages, and limitations of digital complete denture technology. The aim of this review was to offer practical recommendations on indications, clinical procedures and precautions, evaluation metrics, and outcome assessment to support digital restoration of complete denture in clinical practice.
Humans ; Denture, Complete ; Computer-Aided Design ; Denture Design/methods* ; Consensus ; Printing, Three-Dimensional

Alzheimer's disease(AD)is a multifactorial condi-tion characterized by the accumulation of toxic proteins and asso-ciated neurodegeneration.AD is distinguished by the pathologi-cal aggregation of amyloid beta(Aβ)and Tau proteins.The in-teraction between Aβ and Tau can further induce neuroinflamma-tion,mitochondrial autophagy dysfunction,and endoplasmic retic-ulum stress,exacerbating synaptic damage and neuronal death.Neuronal cells are particularly susceptible to protein misfolding due to an imbalance between protein production and degrada-tion.The ubiquitin/26S proteasome system(UPS),a major pathway for protein degradation in eukaryotic cells,plays a cruci-al role in recognizing misfolded or damaged proteins within the nervous system.In UPS,the levels of ubiquitin are tightly regu-lated by both ubiquitin ligases(E3s)and deubiquitylases(DUBs).This article reviews the involvement and mechanisms of E3s and DUBs in the pathogenesis of AD,aiming to provide novel research strategies for its treatment.

This study explores the mechanism of Guben Jiannao Liquid on Alzheimer's disease(AD) by regulating autophagy based on the liver kinase B1(LKB1)/adenosine monophosphate-activated protein kinase(AMPK)/mammalian target of rapamycin(mTOR) pathway. Male SD rats were randomly divided into the blank group, model group, low-dose and high-dose groups of Guben Jiannao Liquid, and rapamycin group, with 10 rats in each group. Except for the blank group, all other groups of rats were injected bilaterally in the hippocampus with β-amyloid(Aβ)_(1-42) to establish the AD model. The low-dose(6.21 g·kg~(-1)) and high-dose(12.42 g·kg~(-1)) groups of Guben Jiannao Liquid and rapamycin group(1 mg·kg~(-1)) were given the corresponding drugs by gavage, and the blank and model groups were given an equal volume of saline by gavage for four weeks. Morris water maze was used to test the learning and memory ability of rats in each group; hematoxylin-eosin(HE) and Nissl staining were used to observe the morphological and quantitative changes of neurons and Nissl bodies in the CA1 region of rat hippocampus; immunohistochemistry was utilized to detect Aβ-positive cell expression in the CA1 region of rat hippocampus; transmission electron microscopy was employed to observe ultrastructural changes in rat hippocampal tissue, and Western blot was used to examine the protein expression levels of LKB1, p-AMPK/AMPK, p-mTOR/mTOR, Beclin1, p62, and LC3-Ⅱ in the hippocampal tissue of the rats. The results showed that compared with those in the blank group, rats in the model group had elevated evasion latency and decreased number of platform transversal and residence time in the platform quadrant. The number of neurons in the hippocampal area was reduced, and the morphology was impaired. The average integral optical density value of Aβ-positive cells was elevated; the expression levels of LKB1, p-AMPK/AMPK, Beclin1, and LC3-Ⅱ were decreased, and the expression levels of p-mTOR/mTOR and p62 were increased. Compared with those in the model group, rats in the low-dose and high-dose groups of Guben Jiannao Liquid had shorter evasion latency, higher number of platform transversal, longer residence time in the platform quadrant, increased number of neurons, decreased expression of Aβ-positive cells and average integral optical density values, and increased number of autophagic lysosomes in hippocampal tissue. The expression levels of LKB1, Beclin1, and LC3-Ⅱ were elevated in the hippocampus of rats in the low-dose group of Guben Jiannao Liquid. The expression levels of LKB1, p-AMPK/AMPK, Beclin1, and LC3-Ⅱ were elevated in the hippocampal tissue of rats in the high-dose group of Guben Jiannao Liquid, and the expression levels of p-mTOR/mTOR and p62 were decreased. The findings suggest that Guben Jiannao Liquid can improve cognitive impairment in AD rats, and its mechanism of action may be related to the activation of the LKB1/AMPK/mTOR signaling pathway and the up-regulation of autophagy level.
Animals ; Alzheimer Disease/physiopathology* ; Male ; TOR Serine-Threonine Kinases/genetics* ; Autophagy/drug effects* ; Rats, Sprague-Dawley ; Protein Serine-Threonine Kinases/genetics* ; AMP-Activated Protein Kinases/genetics* ; Rats ; Drugs, Chinese Herbal/administration & dosage* ; Signal Transduction/drug effects* ; AMP-Activated Protein Kinase Kinases ; Humans ; Hippocampus/metabolism*

Objective:To explore the differences between the Phoenix sepsis scoring system including Phoenix sepsis score (PSS) and Phoenix-8 organ dysfunction score (hereinafter referred to as Phoenix-8) and the commonly used pediatric sepsis scores in evaluating clinical characteristics and prognostic analysis of pediatric patients with severe sepsis diagnosed under traditional standards, namely the diagnostic criteria from the 2005 International Pediatric Sepsis Consensus Conference.Methods:This study was a retrospective observational study. From December 2020 to March 2023, 202 pediatric patients with severe sepsis meeting the inclusion criteria were admitted to the Children's Hospital of Nanjing Medical University. Based on the sepsis diagnostic criteria outlined in the International Consensus Criteria for Pediatric Sepsis and Septic Shock (2024), the pediatric patients were categorized into a sepsis group and a non-sepsis group. Sepsis group was further subdivided into a death subgroup and a survival subgroup based on the outcomes. The age, hospitalization costs, disease outcome indicators (e.g., mortality rate and incidence of septic shock), major organ (e.g., heart, liver, lungs, and kidneys) damage and their correlations, as well as PSS, Phoenix-8 and commonly used pediatric sepsis scores (e.g., pediatric sequential organ failure assessment (pSOFA), pediatric risk of mortality score Ⅲ (PRISM Ⅲ), pediatric logistic organ dysfunction-2 score (PELOD-2), pediatric multiple organ dysfunction score (P-MODS), pediatric critical illness score (PCIS), and pediatric early warning score (PEWS)) were collected and compared. Receiver operating characteristic (ROC) curve and precision-recall curve were plotted to evaluate the predictive ability of PSS, Phoenix-8, and commonly used pediatric sepsis scores for mortality risk in pediatric patients with severe sepsis under traditional standards. Predictive performance was quantified using the area under the ROC curve (AUROC). Univariate logistic regression analysis was employed to quantify the odds ratios of PSS and Phoenix-8 for predicting mortality risk. Patients with severe sepsis under traditional standards were further stratified into subgroups based on complications and comorbidities, including central nervous system (CNS) diseases, multiple infections, cardiovascular system diseases, shock, and malignancies. The Hosmer-Lemeshow goodness-of-fit test was used to assess calibration of PSS and Phoenix-8, and the DeLong test was used to compare whether there were statistically significant differences in the AUROC of PSS and Phoenix-8 for predicting mortality risk among different subgroups of pediatric patients. Results:Compared with those in non-sepsis group, pediatric patients in sepsis group were significantly older ( Z=-2.92, P<0.05) with higher incidences of septic shock and mortality, hospitalization costs, PRISM Ⅲ, PEWS, pSOFA, PELOD-2, PSS, and Phoenix-8 (with χ2 values of 21.28 and 13.64, respectively, Z values of -1.99, -5.33, -5.10, -8.55, -6.91, -10.98, and -9.93, respectively, P<0.05), and lower PCIS ( Z=-3.34, P<0.05). Compared with those in survival subgroup, hospitalization costs, PSS, Phoenix-8, PRISM Ⅲ, PEWS, pSOFA, PELOD-2, and P-MODS of pediatric patients in death subgroup was significantly higher (with Z values of -2.50, -3.50, -2.47, -5.11, -3.84, -2.94, -3.61, and -3.04, respectively, P<0.05). Compared with those in survival subgroup, the incidences of lung damage and liver damage of pediatric patients in death subgroup were also significantly higher (with χ2 values of 6.20 and 10.94, respectively, P<0.05), and 64.7% (97/150) of patients exhibited two or more concurrent organ damage. For predicting mortality risk in pediatric patients with severe sepsis under traditional standards, the AUROC values for PRISM Ⅲ, PCIS, PEWS, pSOFA, PELOD-2, P-MODS, PSS, and Phoenix-8 were approximately 0.70, with optimal cutoff values of 17.5, 91.0, 5.5, 4.5, 2.5, 4.5, 3.5, and 4.5, respectively; PELOD-2 demonstrated the highest sensitivity (0.83); while PRISM Ⅲ, PSS, and Phoenix-8 showed high specificity (>0.80). Univariate logistic regression analysis showed that for every 1-point increase in the PSS within 24 hours of pediatric intensive care unit admission, the relative risk of mortality increased by 63.7% (with odds ratio of 1.64, 95% confidence interval of 1.34-1.99, P<0.05). Similarly, for every 1-point increase in the Phoenix-8, the relative risk of mortality increased by 37.5% (with odds ratio of 1.38, 95% confidence interval of 1.18-1.60, P<0.05). The AUROC values (around 0.80) of PSS and Phoenix-8 for predicting mortality risk in pediatric patients with severe sepsis combined with CNS diseases, multiple infections, and cardiovascular system diseases were relatively high. In contrast, the AUROC values (0.60-0.80) for predicting mortality risk in pediatric patients with severe sepsis combined with shock or malignant tumors were moderate. All models passed the Hosmer-Lemeshow goodness-of-fit test ( P>0.05). The DeLong test indicated no statistically significant differences in predictive ability between PSS and Phoenix-8 across subgroups of pediatric patients ( P>0.05). Conclusions:PSS and Phoenix-8 exhibited higher specificity than most of the commonly used pediatric sepsis scores in predicting mortality risk under traditional standards. Both scores performed much better in predicting the mortality risk in pediatric patients with severe sepsis combined with CNS diseases, multiple infections, and cardiovascular system diseases.

Objective Hypothyroidism is a common clinical disease of systemic metabolic reduction,the incidence and detection rate increased year by year.Based on the clinical characteristics of hypothyroidism,the study constructed and improved animal models to provide reference for the study of hypothyroidism prevention and treatment.Methods By reviewing relevant domestic and foreign literatures,the modeling methods of hypothyroidism were summarized and analyzed.According to the etiology,pathogenesis and clinical diagnostic criteria of hypothyroidism in Chinese medicine and Western medicine,the modeling methods and principles of hypothyroidism animal models were summarized,and the advantages and disadvantages of animal models and the evaluation of clinical conformity were analyzed.Results It was found that the model of drug induction,iodine restriction and 131 I-induced hypothyroidism had high clinical anastomosis in Western medicine,and had the advantages of simple operation,high model formation rate and good repeatability,the combination of the disease model and the syndrome model of kidney yang deficiency and spleen and kidney yang deficiency have a high degree of clinical conformity in TCM.Congenital induced hypothyroidism,autoimmune induced hypothyroidism and genetic induced hypothyroidism can be studied for their unique etiology and pathogenesis,but their clinical manifestations are relatively simple and their clinical anastomosis is relatively low.At present,the construction of hypothyroidism animal model is mainly based on the pathogenesis of Western medicine,and the evaluation of the model mostly relies on laboratory detection indicators.The clinical anastomosis score of traditional Chinese medicine is generally low,and the record of animal apparent indicators is generally insufficient.Conclusion In the process of building hypothyroidism animal model,based on the pathogenesis of traditional Chinese medicine,combining the etiology of traditional Chinese medicine and the pathogenesis of Western medicine,multi-factor comprehensive modeling method can be adopted to increase the record of apparent indicators,improve the accuracy of the four diagnoses and symptoms of traditional Chinese medicine,and systematically and dynamically observe the interaction process of disease and syndrome,so as to build an animal model of hypothyroidism which is more closely aligns with with the clinical characteristics of traditional Chinese medicine and Western medicine.

Purpose To investigate the predictive value of MRI-based peritumoral edema(PE)of lymph node(LN)metastasis burden in patient with invasive breast cancer.Materials and Methods A total of 213 patients in Sichuan Cancer Hospital with invasive breast cancer confirmed by pathology after surgery were enrolled retrospectively from September 2017 to February 2019.Based on the status and number of LN metastases proved by axillary surgery pathology,all patients were divided into high-burden LN metastasis group(n=47 cases,total number of metastatic LN greater than 2)and low-burden LN metastasis group(n=166 cases,total number of metastatic LN less than or equal to 2).T2WI features,including PE type and PE degree,were analyzed.On DCE-MRI,MRI features of breast cancer were analyzed based on BI-RADS.The predictive value of T2WI features and MRI features for LN metastasis burden was assessed by univariate analysis,and the statistically significant features identified by univariate analysis were further subjected to multivariate Logistic regression analysis to establish a prediction model.The model's performance for LN metastasis burden prediction was evaluated via receiver operating characteristic curve,and the predictive metrics were calculated based on the Youden index.Results The rate of high-burden LN metastasis was 22.1%(47/213).The results of univariate analysis showed that PE degree(OR=18.70,P＜0.001),PE type(OR=16.00,P＜0.001),tumor maximum diameter(OR=1.40,P=0.025),and tumor minimum diameter(OR=2.01,P=0.003)were predictive features for high-burden LN metastasis.The multivariate regression analysis showed that the peritumoral edema features,including PE degree(OR=8.02,P＜0.001)and PE type(OR=5.53,P=0.001)were independent predictive features for high-burden LN metastasis.The area under the curve of the final predictive model was 0.842.The diagnostic sensitivity was 0.766,the specificity was 0.861,the positive predictive value was 0.610,and the negative predictive value was 0.929.Conclusion The PE on preoperative MRI have good predictive performance for LN metastasis burden prediction in patient with invasive breast cancer,particularly for low-burden LN metastasis.

Objective:To compare the short-term outcomes of arthroscopic suture bridge technique versus those of arthroscopic tie knot technique in the treatment of tibial avulsion fractures of the anterior cruciate ligament (ACL).Methods:A retrospective study was conducted to analyze the 53 patients with ACL tibial avulsion fracture who had been treated arthroscopically at Department of Sports Medicine, Wuhai People's Hospital between February 2018 and February 2024. There were 31 males and 22 females, with an age of (48.2±5.1) years. The left knee was affected in 27 cases and the right knee in 26 cases. According to the Meyers-Mckeever classification, 32 cases were of type Ⅱ and 21 cases of type Ⅲ. The patients were divided into 2 groups according to different fixation methods: 20 cases were fixed by the arthroscopic tie knot technique (the tie knot group) and 33 cases by the arthroscopic suture bridge technique (the suture bridge group). The operation time and fracture healing time were recorded and compared between the 2 groups. At preoperation, 3 and 6 months after operation, and the last follow-up, the knee pain was evaluated by visual analogue scale (VAS) pain score, the knee stability (side to side disparity) by a KT-1000 arthrometer, and the knee function by The International Knee Documentation Committee (IKDC) subjective score, Lysholm score, knee range of motion, and activities of daily living (ADL) scale. Comparisons were made between and within the 2 groups.Results:The differences in the general preoperative data were not statistically significant between the 2 groups, indicating comparability ( P>0.05). The tie knot group and the suture bridge group were followed up respectively for (13.9±2.1) and (14.5±2.1) months. The surgical time for the suture bridge group [(66.9±8.4) min] was significantly longer than that for the tie knot group [(51.2±6.3) min] ( P<0.05). At 3 months after operation, the VAS pain score [(1.2±0.2) points], side to side disparity [(2.5±0.6) mm], IKDC subjective score [(89.6±1.6) points], Lysholm score [(88.0±1.4) points], knee range of motion (132.1°±2.1°), and ADL score [(88.8±3.3) points] in the suture bridge group were significantly better than those in the tie knot group [(2.1±0.3) points, (3.0±0.9) mm, (87.0±1.4) points, (84.0±1.6) points, 102.1°±2.1°, and (80.3±3.4) points] ( P<0.05). However, there were no significant differences in VAS pain score, side to side disparity, IKDC subjective score, Lysholm score, knee range of motion or ADL score between the 2 groups at 6 months after operation or at the last follow-up ( P>0.05). Statistically significant differences were observed between all time points for VAS pain scores, side-to-side disparity, IKDC subjective scores, Lysholm scores, knee range of motion, and ADL scores in all patients ( P<0.05). No incision infection, nerve injury or other complications occurred in the 2 groups after operation. Conclusions:Both arthroscopic suture bridge technique and arthroscopic tie knot technique are safe and effective intervention options for avulsion fractures of the ACL tibial insertion. The suture bridge technique, with its stable biomechanical properties, can significantly accelerate the process of early postoperative knee function recovery to shorten the recovery period. However, it requires longer surgical time.