Flexible ureteral lithotripsy (FURL) under general anesthesia (GA) is the dominant method in the treatment of renal and upper ureteral calculi，but some patients cannot tolerate GA.In recent years，there has been a growing interest in the use of local anesthesia (LA) as a safe and effective alternative.And it is also an option for patients who have calculi ≤20 mm with high fragility，lower CT value and better compatibility.Before surgery，it is important to conduct relevant examinations，evaluate the status of patients，prevent infections，and indwell ureteral stents.During surgery，lithotomy position，scissors position，prone leg position and other positions should be selected according to the specific conditions of patients.LA drugs should be used to control physiological pain and relieve psychological anxiety.Patients' breathing state should be carefully monitored，and appropriate ureteroscope and lens sheath should be selected for the success and safety of the operation.In this paper，the perioperative management of FURL under LA is briefly summarized，so as to provide reference for clinical practice.

To implement the Opinions of the State Council of the Central Committee of the Communist Party of China on Promoting the Inheritance and Innovative Development of Traditional Chinese Medicine， delve into the diseases specifically responding to traditional Chinese medicine （TCM）， and serve the building of advantageous specialties， clinical talent cultivation， national research layout， and academic innovation， the Chinese Association of Chinese Medicine sponsored the salons in multiple fields to discuss the diseases specifically responding to TCM. On August 26， 2023， the 25^th salon on the diseases specifically responding to TCM was held in Shanghai. In view of the advantages of TCM and integrated traditional Chinese and Western medicine in the diagnosis and treatment of psoriasis， Chinese and western medicine experts and interdisciplinary researchers carried out extensive and in-depth discussions and formed specific suggestions and consensus on the diagnosis and treatment of psoriasis with TCM and integrated traditional Chinese and Western medicine. However， there was still a lack of detailed research path. Under the guidance of the Chinese Association of Chinese Medicine， this paper analyzes the problems in the diagnosis and treatment of psoriasis from the occurrence and development of psoriasis. According to the advantages and characteristics of TCM and integrated traditional Chinese and Western medicine in the diagnosis and treatment of psoriasis， this paper puts forward the main points of research layout for psoriasis from the three aspects of psoriasis diagnosis and treatment， comorbidity prevention， and chronic disease management as follows： ① optimization of the syndrome differentiation system for psoriasis， ② optimization of assessment indicators for psoriasis， ③ recurrence mechanisms of psoriasis， ④ construction and research of TCM prevention and treatment of psoriasis recurrence， ⑤ construction of the comorbidity spectrum and TCM theoretical system of psoriasis， ⑥ comorbidity mechanisms of psoriasis. Furthermore， this article proposed the research layout and directions， expected goals and values， and funding priorities. Therefore， on the basis of the series of salons about psoriasis as a disease specifically responding to TCM， this article puts forward the research paradigm of psoriasis， aiming to facilitate the high-quality development of TCM and provide reference for the national research layout， the research and development of new TCM preparations， the selection of research topics， and the formulation of guidelines and consensus.

Neutrophils, as the most abundant immune cells in the human body, possess the inherent ability to rapidly migrate to sites of inflammation and infection. Novel drug delivery systems leveraging neutrophils capitalize on their natural targeting and phagocytic capabilities to achieve precise drug delivery. Efficient drug loading into neutrophils within neutrophil-based delivery systems can be achieved through physical adsorption, chemical conjugation, and phagocytosis. Design strategies emphasize carrier selection and targeting ligand design to enhance delivery precision. Compared to traditional drug delivery systems, neutrophil-based systems offer significant advantages, including excellent biocompatibility and strong tissue penetration. These properties can significantly improve drug bioavailability and reduce adverse reactions associated with non-target tissue accumulation. However, these systems also face several challenges that require resolution, such as difficulties in cell collection and preservation, the need for stability optimization, challenges in large-scale production, and a lengthy clinical translation cycle. In disease treatment applications, neutrophil-based drug delivery systems enable precise delivery of anti-cancer drugs to tumor sites, potentially disrupting immunosuppression of the tumor microenvironment and enhancing therapeutic efficacy. For brain diseases, their unique ability to cross the blood-brain barrier facilitates effective drug delivery. In chronic inflammatory diseases, neutrophil-based systems can precisely deliver anti-inflammatory agents to mitigate inflammation. Performance enhancements for neutrophil-based systems can be achieved by the development of novel nanomaterials and optimization of targeting ligand affinity, thereby improving the accuracy and efficiency of drug delivery. This review comprehensively explores the design strategies, advantages, challenges, and future directions of neutrophil-based drug delivery systems. It summarizes research progress in disease treatment applica-tions, aiming to offer key insights for the development of novel drug delivery systems and advance precision medicine and targeted therapy.
Humans ; Drug Delivery Systems/methods* ; Neutrophils ; Phagocytosis ; Drug Carriers ; Blood-Brain Barrier ; Neoplasms/drug therapy*

Intestinal fibrosis is a significant clinical challenge in inflammatory bowel diseases, but no effective anti-fibrotic therapy is currently available. Glucagon receptor (GCGR) and glucagon-like peptide 1 receptor (GLP1R) are both peptide hormone receptors involved in energy metabolism of epithelial cells. However, their role in intestinal fibrosis and the underlying mechanisms remain largely unexplored. Herein GCGR and GLP1R were found to be reduced in the stenotic ileum of patients with Crohn's disease as well as in the fibrotic colon of mice with chronic colitis. The downregulation of GCGR and GLP1R led to the accumulation of the metabolic byproduct lactate, resulting in histone H3K9 lactylation and exacerbated intestinal fibrosis through epithelial-to-mesenchymal transition (EMT). Dual activating GCGR and GLP1R by peptide 1907B reduced the H3K9 lactylation in epithelial cells and ameliorated intestinal fibrosis in vivo. We uncovered the role of GCGR/GLP1R in regulating EMT involved in intestinal fibrosis via histone lactylation. Simultaneously activating GCGR/GLP1R with the novel dual agonist peptide 1907B holds promise as a treatment strategy for alleviating intestinal fibrosis.

Mitochondrial dysfunction is a critical factor in the pathogenesis of Alzheimer's disease (AD). The mitochondrial contact site and cristae organizing system (MICOS) plays a pivotal role in shaping the inner mitochondrial membrane, forming cristae junctions and establishing interaction sites between the inner and outer mitochondrial membranes and thereby serving as a cornerstone of mitochondrial structure and function. In the past decade, MICOS abnormalities have been extensively linked to AD pathogenesis. In particular, dysregulated expression of MICOS subunits and mutations in MICOS-related genes have been identified in AD, often in association with hallmark pathological features such as amyloid-β plaque accumulation, neurofibrillary tangle formation, and neuronal apoptosis. Furthermore, MICOS subunits interact with several etiologically relevant proteins, significantly influencing AD progression. The intricate crosstalk between these proteins and MICOS subunits underscores the relevance of MICOS dysfunction in AD. Therapeutic strategies targeting MICOS subunits or their interacting proteins may offer novel approaches for AD treatment. In the present review, we introduce current understanding of MICOS structures and functions, highlight MICOS pathogenesis in AD, and summarize the available MICOS-targeting drugs potentially useful for AD.

Stem cells play a crucial role in maintaining tissue regenerative capacity and homeostasis. However, mechanisms associated with stem cell senescence require further investigation. In this study, we conducted a proteomic analysis of human dental pulp stem cells (HDPSCs) obtained from individuals of various ages. Our findings showed that the expression of NUP62 was decreased in aged HDPSCs. We discovered that NUP62 alleviated senescence-associated phenotypes and enhanced differentiation potential both in vitro and in vivo. Conversely, the knocking down of NUP62 expression aggravated the senescence-associated phenotypes and impaired the proliferation and migration capacity of HDPSCs. Through RNA-sequence and decoding the epigenomic landscapes remodeled induced by NUP62 overexpression, we found that NUP62 helps alleviate senescence in HDPSCs by enhancing the nuclear transport of the transcription factor E2F1. This, in turn, stimulates the transcription of the epigenetic enzyme NSD2. Finally, the overexpression of NUP62 influences the H3K36me2 and H3K36me3 modifications of anti-aging genes (HMGA1, HMGA2, and SIRT6). Our results demonstrated that NUP62 regulates the fate of HDPSCs via NSD2-dependent epigenetic reprogramming.
Humans ; Dental Pulp/cytology* ; Nuclear Pore Complex Proteins/genetics* ; Cellular Senescence/genetics* ; Stem Cells/metabolism* ; Epigenesis, Genetic ; Cell Proliferation ; Cell Differentiation ; Histone-Lysine N-Methyltransferase/metabolism* ; Cells, Cultured ; Cellular Reprogramming ; Cell Movement ; Proteomics

Current experimental and computational methods have limitations in accurately and efficiently classifying ion channels within vast protein spaces. Here we have developed a deep learning algorithm, GPT2 Ion Channel Classifier (GPT2-ICC), which effectively distinguishing ion channels from a test set containing approximately 239 times more non-ion-channel proteins. GPT2-ICC integrates representation learning with a large language model (LLM)-based classifier, enabling highly accurate identification of potential ion channels. Several potential ion channels were predicated from the unannotated human proteome, further demonstrating GPT2-ICC's generalization ability. This study marks a significant advancement in artificial-intelligence-driven ion channel research, highlighting the adaptability and effectiveness of combining representation learning with LLMs to address the challenges of imbalanced protein sequence data. Moreover, it provides a valuable computational tool for uncovering previously uncharacterized ion channels.

Objective It evaluates the high-quality development policies of public hospitals at the provincial level in China,and provides theoretical basis and countermeasures for formulating and optimizing the high-quality develop-ment policies of public hospitals.Methods The ROST CM 6.0 software was used to conduct text mining for 11 sample policies,and the Policy Modeling Consistency(PMC)index model was constructed to evaluate the sample policies quantitatively.Results The average PMC index of 11 sample policies included in the study was 7.16 points,of which 8 were excellent grades and 3 were qualified grades.The first-level variables X5 service system(0.82),X8 Party leadership(0.91)and X6 organization and operation(0.94)scored higher;X2 policy timeliness(0.52),X7 cultural construction(0.68)and X4 service capability(0.71)scored low.Conclusion The content of the high-quality develop-ment policy of public hospitals at the provincial level is basically in line with the national policy,and is relatively excel-lent in the aspects of organization and operation,service system and party leadership,etc.,but there are some weaknesses in the aspects of policy timeliness,cultural construction and service capacity,etc.,which can be op-timized and improved from the aspects of improving service capacity,supplementing long-term policies and strengthening hospital cultural construction.

Objective To explore the high-quality development path of tertiary public hospitals and provide scientific reference for deepening the reform of public hospitals.Methods Based on SPO theory,it constructed an analytical framework for the high-quality development of tertiary public hospitals,collected data of a quarterly monitoring in-dex for the performance assessment and high-quality development of tertiary public hospitals in a certain province in 2023,and analysed 73 tertiary public hospitals participating in the performance assessment as the object of analy-sis,and adopted the fuzzy-set Qualitative Comparative Analysis to explore different condition sets of high-quality de-velopment of tertiary public hospitals and reveal the path of high-quality development of public hospitals.Results High-quality development is the result of multi-factor interaction.Four configurations were identified to promote the high-quality development of tertiary public hospitals:service quality-technology-driven path,service quality-driven path,comprehensive service-driven path,and service quality-benefit-driven path.Quality safety and functional orientation were found to be the core elements in promoting high-quality development of public hospitals.Conclusion Hospitals at all levels should strengthen the guidance of party building,combine with the actual functional positioning,take quality and safety as the core,and optimize the combination conditions of technical level,personnel structure,service process,and cost control.It is essential to clarify the development strategy of hospitals,implement the dynamic concept,and realize the high-quality development of public hospitals.

Objective To empirically analyze the status quo of high-quality development of public hospitals in S Province,provides reference for promoting high-quality development of public hospitals.Methods SPSS 26.0 soft-ware and text analysis method were used to process the high-quality development monitoring data of tertiary public hospitals in S Province,and the qualitative interview results obtained by field investigation were comprehensively ana-lyzed.Results In terms of capacity improvement,public hospitals actively take measures such as the construction of medical union and the reform of payment methods to improve their capacity.Specialized hospitals and maternity and child care hospitals need to be improved in some indicators.In terms of structural optimization,the quality of medi-cal services is high in all regions.The proportion of medical service revenue and the proportion of high-grade surgery still need to be increased.In terms of innovation and efficiency improvement,the application level of electronic medi-cal records has made remarkable progress in various regions.There are differences in the funding of scientific re-search projects.In terms of cultural cohesion,patient satisfaction was higher.There is improvement room in the satisfaction of medical staff.Conclusion Third-level public hospitals in S province have achieved certain results in high-quality de-velopment,but there are still problems,such as the need to further integrate party building work with hospital busi-ness work,the lack of connection between performance incentive and performance evaluation index system,and the need to improve the satisfaction of medical staff.It is necessary to solve the problem and improve the quality and efficiency of medical service.