Distinct from the complementary inhibition mechanism through binding to the target with three-dimensional conformation of small molecule inhibitors, targeted protein degradation technology takes tremendous advantage of endogenous protein degradation pathway inside cells to degrade plenty of “undruggable” target proteins, which provides a novel route for the treatment of many serious diseases, mainly including proteolysis-targeting chimeras, lysosome-targeting chimeras, autophagy-targeting chimeras, antibody-based proteolysis-targeting chimeras, etc. Unlike proteolysis-targeting chimeras first found in 2001, which rely on ubiquitin-proteasome system to mainly degrade intracellular proteins of interest, lysosome-targeting chimeras identified in 2020, which was act as the fastly developing technology, utilize cellular lysosomal pathway through endocytosis mediated by lysosome-targeting receptor to degrade both extracellular and membrane proteins. As an emerging biomedical technology, nucleic acid-driven lysosome-targeting chimeras utilize nucleic acids as certain components of chimera molecule to replace with ligand to lysosome-targeting receptor or protein of interest, exhibiting broad application prospects and potential clinical value in disease treatment and drug development. This review mainly introduced present progress of nucleic acid-driven lysosome-targeting chimeras technology, including its basic composition, its advantages compared with antibody or glycopeptide-based lysosome-targeting chimeras, and focused on its chief application, in terms of the type of lysosome-targeting receptors. Most research about the development of nucleic acid-driven lysosome-targeting chimeras focused on those which utilized cation-independent mannose-6-phosphonate receptor as the lysosome-targeting receptor. Both mannose-6-phosphonate-modified glycopeptide and nucleic aptamer targeting cation-independent mannose-6-phosphonate receptor, even double-stranded DNA molecule moiety can be taken advantage as the ligand to lysosome-targeting receptor. The same as classical lysosome-targeting chimeras, asialoglycoprotein receptor can also be used for advance of nucleic acid-driven lysosome-targeting chimeras. Another new-found lysosome-targeting receptor, scavenger receptor, can bind dendritic DNA molecules to mediate cellular internalization of complex and lysosomal degradation of target protein, suggesting the successful application of scavenger receptor-mediated nucleic acid-driven lysosome-targeting chimeras. In addition, this review briefly overviewed the history of lysosome-targeting chimeras, including first-generation and second-generation lysosome-targeting chimeras through cation-independent mannose-6-phosphonate receptor-mediated and asialoglycoprotein receptor-mediated endocytosis respectively, so that a clear timeline can be presented for the advance of chimera technique. Meantime, current deficiency and challenge of lysosome-targeting chimeras was also mentioned to give some direction for deep progress of lysosome-targeting chimeras. Finally, according to faulty lysosomal degradation efficiency, more cellular mechanism where lysosome-targeting chimeras perform degradation of protein of interest need to be deeply explored. In view of current progress and direction of nucleic acid-driven lysosome-targeting chimeras, we discussed its current challenges and development direction in the future. Stability of natural nucleic acid molecule and optimized chimera construction have a great influence on the biological function of lysosome-targeting chimeras. Discovery of novel lysosome-targeting receptors and nucleic aptamer with higher affinity to the target will greatly facilitate profound advance of chimera technique. In summary, nucleic acid-driven lysosome-targeting chimeras have many superiorities, such as lower immunogenicity, expedient synthesis of chimera molecules and so on, in contrast to classical lysosome-targeting chimeras, making it more valuable. Also, the chimera technology provides new ideas and methods for biomedical research, drug development and clinical treatment, and can be used more widely through further research and optimization.

Objective:To investigate the expression of erythropoietin-producing hepatocyte kinase receptor A10 (EphA10) in gastric cancer and adjacent tissues, and analyze its correlation with clinical features and prognosis.Methods:The clinical data of 112 patients with gastric cancer from January 2018 to December 2023 in Eastern Theater Command Air Force Hospital were retrospectively analyzed. The expression of EphA10 in gastric cancer and adjacent tissues was detected by EnVision immunohistochemical staining. The relationship between EphA10 expression and clinicopathological features was analyzed. The Kaplan-Meier survival curve was drawn, and the comparison used the log-rank test. Multivariate Cox regression was used to analyze the independent risk factors of the overall survival time in patients with gastric cancer.Results:The positive expression rate of EphA10 in gastric cancer tissues was significantly higher than that in adjacent tissues: 44.6% (50/112) vs. 0, and there was statistical difference ( χ2 = 64.37, P<0.01). In patients with gastric cancer, the positive expression of EphA10 in gastric cancer tissues was correlated with tumor long diameter, differentiation, TNM stage and lymph node metastasis ( P<0.01 or <0.05), but without age, gender and distant metastasis ( P>0.05). Kaplan-Meier survival curve analysis result showed that the median overall survival time in patients with positive EphA10 expression was significantly lower than that in patients with negative EphA10 expression: 18 months vs. 48 months, and there was statistical difference (log-rank χ2 = 53.66, P<0.01). Multivariate Cox regression analysis result showed that tumor long diameter ≥3 cm, TNM stage Ⅲ to Ⅳ, lymph node metastasis and EphA10 positive expression were the independent risk factors of the overall survival time in patients with gastric cancer ( HR = 1.250, 1.515, 1.321 and 0.831; 95% CI 1.143 to 1.368, 1.267 to 1.813, 1.168 to 1.497 and 0.756 to 0.913; P<0.01 or <0.05). Conclusions:The expression level of EphA10 in gastric cancer tissues is up-regulated, and its expression level is correlated with the clinicopathological features. EphA10 can be used as one of the reference indicators for clinical prognosis evaluation in patients with gastric cancer.

Objective To explore the effect of exercise under cold exposure on hepatic protein ki-nase B(AKT)/forkhead box O1(FoxO1)expression in obese rats.Methods Among rats successfully induced nutritional obesity by high-fat diet,forty were selected and randomly divided into a normal-temperature control group(NC,n=10),a normal-temperature exercise group(NE,n=10),a sus-tained-cold control group(SC,n=10),and a sustained-cold exercise group(SE,n=10).The normal temperature was kept at 25°C±1°C,while the low temperature remained at 4°C±1°C,with 50%to 60%relative humidity.The exercise protocol was every other day at a speed of 25 m/min for 2 sets of 30 min each,with an interval of 10 minutes.After 5 weeks,glucose and insulin tolerance were tested by oral glucose tolerance test(OGTT)and insulin tolerance test insulin tolerance test(ITT).Then,all rats were weighed and sacrificed,then taken blood from the abdominal aorta to sepa-rate serum,followed by detection of serum alanine aminotransferase(ALT)and aspartate aminotransfer-ase(AST)levels using fully automatic biochemical analyzer.Moreover,livers were weighed to calcu-late the liver index.Meanwhile,the mRNA expressions of hepatic AKT,FoxO1 and PEPCK were de-tected using RT-qPCR,while the protein expressions of AKT,phosphorylated protein kinase B(p-AKT),and FoxO1 in the liver were measured using Western blotting.Results(1)The average body weights of the NE,SC and SE groups were significantly lower than the NC group(P<0.01),with that of the SC and SE groups significantly lower than the NE group(P<0.01).(2)Compared with the NC group,the area under the OGTT curve of the SC group decreased(P<0.01).Moreover,the area under the ITT curve of the SE group was significantly lower than the other 3 groups(P<0.01,P<0.01,P<0.05),with that of the NE and SC groups significantly lower than the NC group(P<0.05,P<0.01).(3)The liver indices of the NE,SC and SE groups were all significantly lower than the NC group(P<0.01),while the serum ALT level of the NE group was significantly lower than the NC and SE groups(P<0.05),with that of the SC group significantly lower than the NC group(P<0.01).(4)Compared with the NC group,hepatic AKT mRNA expression increased significantly in the SE group(P<0.05),while the hepatic FoxO1 and PEPCK mRNA expression decreased significantly in the other three groups(P<0.01).(5)Compared with the NC group,the liver AKT protein phosphorylation levels were significantly higher in the other three groups(P<0.05,P<0.05,P<0.01),while the FoxO1 protein expression decreased significantly(P<0.05,P<0.01,P<0.01).(6)Body mass,liver FoxO1,PEPCK mRNA expression,AKT protein phosphorylation level and FoxO1 protein expression level of obese rats were affected by cold exposure,exercise and cold exposure+exercise,and the liver index and serum ALT level were done by exercise and cold exposure+exercise.However,the area un-der the ITT curve and liver AKT mRNA content were impacted by cold exposure and exercise,while that under the OGTT curve was influenced by cold exposure and cold exposure+exercise.Conclu-sion Exercise under cold exposure can activate hepatic AKT/FoxO1 signaling pathway,protect liver function,increase insulin sensitivity,and effectively improve glucose metabolism in obese rats.

Autism spectrum disorder(ASD),characterized by unknown etiology and high heterogeneity,ne-cessitates precise diagnostic and intervention strategies.Neuroimaging techniques have shown great promise in un-covering the neural mechanisms of ASD,providing a foundation for aided diagnosis and transcranial magnetic stim-ulation(TMS)interventions.This review highlights that integrating multimodal neuroimaging and developing indi-vidualized indices with developmental specificity can significantly improve the accuracy of ASD diagnosis and clas-sification.Furthermore,TMS interventions guided by functional connectivity derived from functional magnetic reso-nance imaging(fMRI)offer a personalized approach to ASD treatment.

Objective:To explore the causes of lack of compliance with life care in hematopoietic stem cell transplantation recipients while living alone in the transplant warehouse, and to provide a basis for developing targeted promotion measures.Methods:Using purposive sampling method, from June to December 2023, on-site observations were conducted on the voluntary completion of life care by hematopoietic stem cell transplant patients (with a 30 day observation period) admitted to the Blood Transplantation Center of the First Affiliated Hospital of Wenzhou Medical University. The compliance was calculated after the observation period. Patients with a compliance of less than 80% were selected, and semi-structured interviews were conducted with 17 of them after informed consent. The Colaizzi 7-step analysis method was applied to organize and analyze the interview data.Results:Three core themes on lack of compliance were distilled, namely physical factors impeding compliance (somatic specific symptoms leading to distraction, somatic non-specific symptoms leading to activity intolerance), psychological factors impeding compliance (negative emotions, comfort zone dilemmas, regression phenomena, constraints of personality psychological traits), and cognitive factors impeding compliance (subjective cognitive unperceived benefit, poor modeling resulting in cognitive biases, limited perceived attention) .Conclusions:The behavioral causes of lack of compliance with life care of hematopoietic stem cell transplant patients while living alone in the transplant warehouse are due to multiple factors of the body and mind, among which psychologically mediated mechanisms are key to compliance. Healthcare professionals should pay attention to both the physiological and psychological needs of patients, actively alleviate physical symptoms, appropriately provide psychological care to remove psychological barriers, help them actively seek family and social support, and promote cognitive improvement, thereby improving compliance.

Objective:To investigate the current status of convex baseplate selection and use among clinical nurses.Methods:A convenience sampling method was employed to survey 1 873 nurses from 180 hospitals across China between November and December 2024 using a general information questionnaire and a self-designed questionnaire on convex baseplate selection and use. A total of 1 873 questionnaires were distributed, and 1 860 valid responses were collected, yielding a response rate of 99.31% (1 860/1 873) .Results:Among the 1 860 nurses, 88.98% (1 655/1 860) had access to convex baseplates in clinical practice. However, only 8.82% (146/1 655) used them immediately postoperatively, and only 4.53% (75/1 655) chose convex baseplates without considering any product features. The five common clinical indications for convex baseplate use included stoma retraction (96.62%, 1 599/1 655) , peristomal skin folds or depressions (96.56%, 1 598/1 655) , flush stomas (80.12%, 1 326/1 655) , leakage (70.03%, 1 159/1 655) , and abdominal laxity (66.89%, 1 107/1 655) . Common contraindications for use included peristomal varicose veins (77.46%, 1 282/1 655) , peristoma pressure injuries (75.35%, 1 247/1 655) , stoma prolapse (74.50%, 1 233/1 655) , parastomal hernia (72.87%, 1 206/1 655) , and pyoderma gangrenosum (67.01%, 1 109/1 655) . Key assessment areas when selecting convex baseplates included the stoma itself (97.28%, 1 610/1 655) , peristomal skin (96.50%, 1 597/1 655) , abdominal wall contour (95.41%, 1 579/1 655) , excretion patterns (87.37%, 1 446/1 655) , and previous convex baseplate use (82.36%, 1 363/1 655) . Measures commonly used by nurses to enhance adhesion included the use of stoma belts (95.29%, 1 577/1 655) , barrier rings or paste (94.80%, 1 569/1 655) , smoothing peristomal skin folds (90.57%, 1 499/1 655) , advising patients to limit bending (82.96%, 1 373/1 655) , and abdominal binders (57.28%, 948/1 655) .Conclusions:The clinical application of convex baseplates requires further promotion. Nursing administrators should strengthen training on the selection, characteristics, and indications of convex baseplates, with particular emphasis on the understanding of the five key product features.

In June 2022, the Journal of Wound, Ostomy and Continence Nursing published the use of a convex pouching system in the postoperative period: a national consensus (hereinafter referred to as the "consensus") . The consensus recommends the use of convex ostomy products immediately after surgery and within the first six months following ostomy formation. It also establishes principles for selecting the most appropriate ostomy product for patients. This article interprets the background and significance of the consensus and highlights its key points, aiming to provide a reference for the standardized use of convex ostomy products postoperatively.

The classification of stoma skin barriers varies based on their specific features. The curvature design of convex skin barriers provides a secure and effective seal for patients with flat, retracted stomas or peristomal skin folds. The secure sealing ability of convex skin barriers is attributed to several critical structural components. Although convex skin barriers offer many clinical advantages, there is currently no unified standard for measuring their characteristics, resulting in confusion among healthcare professionals when selecting stoma care products. To address this issue, the 2021 International Stoma Care Expert Meeting proposed the Expert Consensus on Characteristics of Convex Skin Barriers and Clinical Application, which clearly defines five essential properties and clinical application guidelines for convex barriers. However, as most consensus contributors are from Europe and North America, its applicability in Chinese healthcare settings may be limited. Therefore, this paper provides a detailed interpretation of the five characteristics and clinical application statements of convex skin barriers, aiming to offer practical guidance to clinical nurses in selecting appropriate convex products and managing stoma-related complications.

Autism spectrum disorder(ASD),characterized by unknown etiology and high heterogeneity,ne-cessitates precise diagnostic and intervention strategies.Neuroimaging techniques have shown great promise in un-covering the neural mechanisms of ASD,providing a foundation for aided diagnosis and transcranial magnetic stim-ulation(TMS)interventions.This review highlights that integrating multimodal neuroimaging and developing indi-vidualized indices with developmental specificity can significantly improve the accuracy of ASD diagnosis and clas-sification.Furthermore,TMS interventions guided by functional connectivity derived from functional magnetic reso-nance imaging(fMRI)offer a personalized approach to ASD treatment.