Copper is a trace element in the human body and is closely related to various signaling pathways and tumor-related biological behaviors. However， when its concentration exceeds the threshold maintained by homeostatic mechanisms， it becomes toxic and triggers cell death. Cuproptosis is a novel form of cell death， distinct from all other known cell death pathways. It occurs through the direct binding of copper to the lipoic acid components of the tricarboxylic acid cycle， leading to the aggregation of lipoic-acylated proteins and the loss of iron-sulfur cluster proteins. This triggers protein toxicity stress， ultimately resulting in cell death. Cuproptosis plays a role in the occurrence， development， and prognosis of digestive tract tumors. Noncoding RNAs （ncRNAs） such as long non-coding RNA （lncRNA）， micro RNA （miRNA） and circular RNA （circRNA） directly or indirectly regulate the expression of cuproptosis-related genes （FDX1，LIPT1，LIAS，DLD，DLAT，PDHA1，PDHB，MTF1，GLS and CDKN2A） in digestive tract tumors based on ceRNA mechanism， thereby inducing copper ion accumulation， driving oxidative stress response， protein fatty acylation and ubiquitin-proteasome system， inhibiting the occurrence and development of digestive tract tumor cells. NcRNAs’ implication in the genesis of tumor cells via regulating cuproptosis-related genes provides a new insight into precision-targeted therapy for tumors. This article introduces cuproptosis， outlines the various regulatory mechanisms of cuproptosis， and provides an overview of ncRNAs and their roles. It reviews recent research on ncRNAs involved in regulating cuproptosis in digestive tract tumors such as esophageal squamous cell carcinoma， gastric cancer， hepatocellular carcinoma， colorectal carcinoma， pancreatic cancer， along with their molecular mechanisms. The article also presents clinical perspectives， aiming to provide a theoretical basis for the diagnosis and treatment of digestive tract tumors.

With the extensive application of nuclear technology in industry, agriculture, and medicine, the safety issues associated with neutron radiation have become increasingly prominent. Due to their high penetrability and strong ionization effect, neutrons can cause serious health risks by directly damaging DNA or inducing secondary γ radiation. Therefore, the neutron radiation protection has become a core challenge in radiation protection, especially the research and development of neutron shielding materials. To ensure the safe development of nuclear technology, neutron shielding materials are indispensable and constitute a fundamental core technology for radiation protection. This paper reviews the theory of neutron radiation protection and the research progress of neutron shielding materials, with a focus on the current application status and existing problems of neutron shielding materials. This article also discusses the future development trends. This review aims to provide theoretical support and technical references for the safe application and development of nuclear technology.

OBJECTIVES: To investigate the mechanism through which salidroside inhibits proliferation of gastric cancer (GC) cells focusing on glucose metabolic reprogramming pathways. METHODS: High-throughput sequencing combined with bioinformatics analysis was employed to identify the potential targets of salidroside in human GC MGC-803 cells. Liposome-mediated transfection experiments were carried out to validate the functional and mechanistic roles of these targets. CCK-8 and colony formation assays were used to assess the effects of salidroside on GC cell viability and clonogenic ability. qRT-PCR, Western blotting, and biochemical assay kits were used to analyze the regulatory effects of salidroside on the miR-1343-3p-OGDHL/PDHB enzyme complex-pyruvate metabolic pathway in GC cells. RESULTS: Bioinformatics analysis suggested that the tumor-suppressive factor miR-1343-3p negatively regulated the key glycolytic enzyme gene oxoglutarate dehydrogenase-like (OGDHL) in GC cells, and OGDHL and pyruvate dehydrogenase E1 subunit beta (PDHB) were both significantly upregulated in GC tissues, which was close by correlated with reduced survival rates of GC patients. In MGC-803 cells, salidroside treatment significantly enhanced the expression level of miR-1343-3p and downregulated OGDHL expression, resulting in disruption of the stability of PDHB, reduced pyruvate oxidative decarboxylation, and consequently decreased production of acetyl-CoA and ATP. CONCLUSIONS Salidroside inhibits GC cell proliferation possibly by regulating the miR-1343-3p-OGDHL/PDHB enzyme complex-pyruvate metabolic pathway, which provides new insights into its anti-tumor mechanisms and suggests new strategies for targeted therapy for GC.
Humans ; Stomach Neoplasms/pathology* ; MicroRNAs/genetics* ; Cell Proliferation/drug effects* ; Glucosides/pharmacology* ; Phenols/pharmacology* ; Cell Line, Tumor ; Glucose/metabolism* ; Pyruvate Dehydrogenase (Lipoamide)/metabolism*

Loss-of-function variants in CSDE1 have been strongly linked to neuropsychiatric disorders, yet the precise role of CSDE1 in neurogenesis remains elusive. In this study, we demonstrate that knockout of Csde1 during cortical development in mice results in impaired neural progenitor proliferation, leading to abnormal cortical lamination and embryonic lethality. Transcriptomic analysis revealed that Csde1 upregulates the transcription of genes involved in the cell cycle network. Applying a dual thymidine-labelling approach, we further revealed prolonged cell cycle durations of neuronal progenitors in Csde1-knockout mice, with a notable extension of the G1 phase. Intersection with CLIP-seq data demonstrated that Csde1 binds to the 3' untranslated region (UTR) of mRNA transcripts encoding cell cycle genes. Particularly, we uncovered that Csde1 directly binds to the 3' UTR of mRNA transcripts encoding Cdk6, a pivotal gene in regulating the transition from the G1 to S phases of the cell cycle, thereby maintaining its stability. Collectively, this study elucidates Csde1 as a novel regulator of Cdk6, sheds new light on its critical roles in orchestrating brain development, and underscores how mutations in Csde1 may contribute to the pathogenesis of neuropsychiatric disorders.
Animals ; Neurogenesis/genetics* ; Cell Cycle/genetics* ; Mice, Knockout ; Mice ; Neural Stem Cells/metabolism* ; DNA-Binding Proteins/metabolism* ; Cyclin-Dependent Kinase 6/genetics* ; Cell Proliferation ; 3' Untranslated Regions ; Cerebral Cortex/embryology* ; RNA-Binding Proteins ; Mice, Inbred C57BL

Objective To investigate the effect of Danshen Baoxin Cha (DBC) on a rat model of coronary heart disease combined with cognitive impairment. Methods Male Sprague-Dawley(SD) rats were randomly assigned to two groups:normal group and model group. Streptozotocin was injected into the bilateral ventricles of rats in the model group to establish cognitive impairment model,then isoproterenol hydrochloride was injected subcutaneously to model myocardial ischemia. Behavioral experiments were conducted to verify the success of the model of cognitive dysfunction. The rats of the model group were randomly divided into five groups:model control group,Tongxinluo Capsule group (TXL group,1.6 g·kg-1),and low-(4 g·kg-1),medium-(8 g·kg-1),and high-(16 g·kg-1) dose DBC groups. These groups were received the respective treatments continuously for two weeks. Subsequently,the Y-maze,novel object recognition and Morris water maze experiment were employed to assess the learning and memory abilities of rats. A kit was utilized to quantify the level of oxidative stress in the brain and the adenosine triphosphate (ATP) content in the brain and mitochondria. Hematoxylin-eosin (HE) staining and Nissl staining were employed to observe the pathological changes of neurons in hippocampus CA1 region. Electron microscopy was utilized to observe the pathological changes of mitochondria in hippocampal CA1 region. The expression levels of peroxisome proliferator-activated receptor γ coactivator-1α(PGC-1α),glucose transporter type 4(GLUT4),and optic atrophy 1(OPA1) were quantified by real-time fluorescence quantitative polymerase chain reaction (PCR),and the expression of proteins related to the AMPK/OPA1 signaling pathway was determined by Western Blot analysis. Results Compared with the normal group,the spontaneous alternating reaction rate,the novel object recognition index,number of crossing the original platform,and distance ratio in the model group were obviously decreased (P<0.01). Neuronal density in the CA1 region of the hippocampus was decreased,Nissl bodies were decreased,and nucleus consolidation was increased. The ATP level in mitochondria,and the levels of ATP,SOD,and GSH-PX in brain were significantly decreased(P<0.05,P<0.01),as well as the content of ROS and MDA were significantly increased (P<0.05,P<0.01). The mitochondria of hippocampus in CA1 region were swollen,with sparse and vacuolated cristae. The mRNA expression levels of GLUT4,PGC-1α,and OPA1 were significantly decreased (P<0.01). The protein expression levels of GLUT4,SIRT1,PGC-1α and OPA1,and p-AMPK/AMPK ratio were significantly decreased (P<0.05,P<0.01). Compared with the model group,the behavioral indexes of rats in the DBC groups were significantly improved (P<0.05,P<0.01),the number of neurons in the hippocampal CA1 area,Nissl bodies and nucleus consolidation were improved. The ATP level in mitochondria and the levels of ATP,SOD,and GSH-PX in brain were significantly increased (P<0.05,P<0.01). The levels of ROS and MDA were significantly decreased (P<0.05,P<0.01). The structure of mitochondrial cristae in hippocampal CA1 region were relatively intact. The mRNA expression levels of GLUT4,PGC-1α and OPA1 were increased (P<0.05,P<0.01),and the expression of proteins related to the AMPK/OPA1 signaling pathway was significantly increased(P<0.05,P<0.01). Conclusion DBC can enhance learning and memory abilities,reduce neuronal damage in a rat model of coronary heart disease combined with cognitive impairment. The mechanism may be related to the reduction of oxidative stress damage in the brain,the activation of the AMPK/OPA1 signaling pathway,and the restoration of energy levels.

Objective:To analyze the clinical situation of critically ill children with Montgomery T-tube，aiming to summarize the characteristics of T-tube application in pediatric and the experience of postoperative airway management in PICU.Methods:The etiology，clinical characteristics，complications and ICU admissions of patients with Montgomery T-tube admitted to the Pediatric Hospital of Fudan University from April 2019 to December 2021 were analyzed，and the application of T-tube in patients with critical conditions requiring long-term mechanical ventilation was described in the light of clinical experience.Results:During the study period,seven children were admitted to the PICU after T-tube insertion,including three males and four females,aged 9~75 months.Five children received mechanical ventilation.Among them,there were five cases with congenital laryngeal malformations,one case with tracheoesophageal fistula,and one case with laryngeal papilloma.The main complications were sputum blockage,infection,and granulation proliferation.One child died of secretion blockage,while the other children were successfully evacuated from the T-tube.The longest retention time of the T-tube was 367 days.Five patients experienced hoarseness after removing the T-tube,and upon re-examination with fiberoptic bronchoscopy,no recurrence of subglottic stenosis was observed.There was no respiratory distress or wheezing,and there were no abnormalities observed during regular outpatient follow-up after discharge.After discharge,the quality of life of the six surviving children improved compared to preoperative,and they all resumed oral feeding.There were no complaints of swallowing difficulties or aspiration during outpatient follow-up.But they were all combined with malnutrition.Conclusion:The Montgomery T-tube is a secure and dependable airway stent utilized for airway remodeling and the maintenance of airway patency following interventional surgery.For critically ill children,early management of airway clearance and infection prevention are imperative.

AIM:To investigate the effect of Huangqi-Danggui decoction(HQDG)on the brain tissue of rats with cerebral ischemia/reperfusion(I/R)injury for 7 d by regulating macroautophagy and chaperone-mediated autophagy(CMA),and to explore its mechanism.METHODS:Male SD rats were randomly divided into sham group,model group,HQDG group and Xuesaitong(XST)group.Determination of main chemical components of HQDG by liquid chro-matography-mass spectrometry.The model of middle cerebral artery occlusion/reperfusion in rats was established by the left modified thread embolism method,and the changes of cerebral blood flow were observed by laser speckle blood flow imager.Zea Longa score was used to observe the neurological deficit.HE staining was used to observe the degree of nerve cell injury.The changes of neurovascular unit and autophagosomes in brain tissue were observed by transmission electron microscopy.Immunohistochemical method was used to detect the expression of LC3,P62,lysosome-associated membrane protein-2A(LAMP-2A),heat shock protein 70(HSP70)and myocyte enhancer factor 2D(MEF2D)proteins.Western blot was used to detect the expression of autophagy-related proteins P62 and LC3-Ⅱ/LC3-I.RESULTS:Compared with the sham group,the neurological deficit score in model group was significantly higher(P<0.01).A large number of nerve cells showed necrosis and nuclear dissolution,with the cell arrangement being disordered.The number of autophagosomes increased.The protein expression levels of LC3,LAMP-2A,HSP70 and MEF2D in brain tissue increased,while the ex-pression level of P62 protein decreased(P<0.05 or P<0.01).Compared with the model group,the scores of neurological deficit in brain tissue in HQDG and XST groups were significantly lower(P<0.01).Cell damage was significantly re-duced.The number of autophagosomes further increased.The expression levels of LAMP-2A,HSP70,MEF2D and P62 proteins in brain tissue decreased,while the expression levels of LC3-Ⅱ/LC3-I protein increased(P<0.05 or P<0.01).CONCLUSION:HQDG can alleviate cerebral ischemia/reperfusion injury in rats and exert neuroprotective effects by ac-tivating macroautophagy and reducing CMA.

Objective:To explore the definition and connotation of the thriving in the elderly, so as to provide reference for clinical practice.Methods:This study systematically searched databases such as China National Knowledge Infrastructure, WanFangdata, CINAHL, PsycINFO, PubMed, and Web of Science using keywords such as "aged" and "thriving". The search period was from database establishment to June 10, 2023. Walker's eight-step analysis method was used to conduct concept analysis on the thriving in the elderly.Results:A total of 14 articles were included. The defining attributes of the thriving in the elderly included good self-perception, utilizing existing resources to adjust self-expectation, and achieving self-growth and development. The antecedents were a positive attitude, high-quality caregivers and care services, a good physical and humanistic environment. The consequence was that elderly people had great adaptability, subjective experience, and health level.Conclusions:The thriving in the elderly is a subjective well-being achieved by the interaction among an individual, the humanistic and physical environment, which is affected by various factors such as individuals and environment. It is a new concept that has emerged in the international field of geriatric nursing in recent years, focusing on the positive aspects of aging and providing new directions for research in geriatric nursing.

Objective: To investigate the impact of childhood traumatic experiences on individual risktaking decisions in early adulthood using functional nearinfrared spectroscopy (fNIRS), so as to provide the reference for clarifying the brain mechanisms underlying the impact of childhood trauma on individual risky decision. Methods: From December 2023 to March 2024, 28 children with childhood trauma experiences (trauma group) and 32 healthy college students (control group) were selected from Jining Medical University by a combination of stratified descent and convenient sampling methods. All subjects participated in the Iowa Game task fNIRS scanning. The brain activation, functional connectivity, graph theory properties (degree centrality, betweenness centrality, and local efficiency), and Receiver Operating Characteristic (ROC) analysis were performed by using preprocessing fNIRS data. Results: Compared with control group, trauma group showed significantly fewer choice times in the inferior deck (Z=-0.88), and showed significantly decreased activation levels in the right frontalpolar (Z=-2.59), as well as showed significant decreased functional connectivity between left dorsolateral prefrontal and in right dorsolateral prefrontal (Z=-3.78), and between left dorsolateral prefrontal cortex and the right frontal pole (Z=-3.68)(P<0.05). The central index of right inferior frontal gyrus in the trauma group was higher than that in the control group, while the central index of left and right dorsolateral frontal lobes was lower than that in the control group (Z=2.13, -2.53, -2.12, P<0.05). The centrality index of the right inferior frontal gyrus in the trauma group was higher than that in the control group (Z=2.47, P<0.05). The local efficiency indicators of the right inferior frontal gyrus, left and right frontal pole in the trauma group were higher than those in the control group (Z=2.51, 2.17, 2.53, P<0.05). The results of the ROC curve analysis showed that the local efficiency achieved the highest area under the curve (AUC=0.68). Conclusions Young adults with childhood trauma experience tend to choose lower loss, and the frontal pole shows a lack of activation in the whole process of risk decision performance. The abnormalities in the brain connectivity and network properties might be the neural basis of excessive defense mechanisms that childhood trauma leads to risky decisions.

ObjectiveThis study aimed to evaluate the clinical efficacy of Ruyi Zhenbaowan（RYZBW）in the treatment of initial and early knee osteoarthritis （KOA） through a prospective multicenter，randomized，double-blind，and placebo-parallel controlled trial. MethodFrom October 13^th， 2021 to December 25^th， 2021， 240 KOA subjects meeting the acceptance criteria were enrolled in 15 sub-centers including Wangjing Hospital， Chinese Academy of Chinese Medical Sciences， and they were randomly divided into observation group and control group， with 120 cases in each group. The intervention measures for the observation group were RYZBW + health education， and the intervention measures for the control group were RYZBW placebo + health education. The intervention period in both groups was four weeks， and they were followed up for four weeks after the intervention. The primary outcome measure was the total score of Western Ontario and McMaster University Osteoarthritis Index score （WOMAC score）， and the secondary outcome measures were the response rate of visual scale （VAS） pain score， WOMAC sub item scores （joint pain， joint stiffness， and joint function）， quality of life （SF-12） score， and traditional Chinese medicine （TCM） syndrome score. Result（1） Efficacy evaluation. The marginal model results showed that the observation group was better than the control group in improving the WOMAC total score and WOMAC pain score in the treatment of KOA with RYZBW， and the difference was statistically significant （P<0.05）. There was no significant difference between the two groups in improving VAS score response rate， WOMAC function score， WOMAC stiffness score， SF12-PCS （quality of life-physical health） score， SF12-MCS （quality of life-mental health） score， and TCM syndrome score. （2） Subgroup analysis. ① In terms of VAS score response rate， the response rate of the observation group was higher than that of the control group for subjects with baseline VAS score of （4， 5］， and the difference was statistically significant （P<0.05）. ② In terms of TCM syndrome score， for subjects aged ［56， 60］ and ［61， 65］， the decrease in total TCM syndrome score in the observation group was better than that in the control group， and the difference was statistically significant （P<0.05）. ConclusionTibetan medicine RYZBW has good clinical efficacy in improving WOMAC total score， VAS score response rate， WOMAC pain score， WOMAC function score， and TCM syndrome score for patients with initial and early KOA， which can fill the lack of Tibetan medicine RYZBW in the treatment of KOA and make a demonstration study for the inheritance and development of ethnic medicine.