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.

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

BACKGROUND: The primary limitation to kidney transplantation is organ shortage. Recent progress in gene editing and immunosuppressive regimens has made xenotransplantation with porcine organs a possibility. However, evidence in pig-to-human xenotransplantation remains scarce, and antibody-mediated rejection (AMR) is a major obstacle to clinical applications of xenotransplantation. METHODS: We conducted a kidney xenotransplantation in a brain-dead human recipient using a porcine kidney with five gene edits (5GE) on March 25, 2024 at Xijing Hospital, China. Clinical-grade immunosuppressive regimens were employed, and the observation period lasted 22 days. We collected and analyzed the xenograft function, ultrasound findings, sequential protocol biopsies, and immune surveillance of the recipient during the observation. RESULTS: The combination of 5GE in the porcine kidney and clinical-grade immunosuppressive regimens prevented hyperacute rejection. The xenograft kidney underwent delayed graft function in the first week, but urine output increased later and the single xenograft kidney maintained electrolyte and pH homeostasis from postoperative day (POD) 12 to 19. We observed AMR at 24 h post-transplantation, due to the presence of pre-existing anti-porcine antibodies and cytotoxicity before transplantation; this AMR persisted throughout the observation period. Plasma exchange and intravenous immunoglobulin treatment mitigated the AMR. We observed activation of latent porcine cytomegalovirus toward the end of the study, which might have contributed to coagulation disorder in the recipient. CONCLUSIONS 5GE and clinical-grade immunosuppressive regimens were sufficient to prevent hyperacute rejection during pig-to-human kidney xenotransplantation. Pre-existing anti-porcine antibodies predisposed the xenograft to AMR. Plasma exchange and intravenous immunoglobulin were safe and effective in the treatment of AMR after kidney xenotransplantation.
Transplantation, Heterologous/methods* ; Kidney Transplantation/methods* ; Heterografts/pathology* ; Immunoglobulins, Intravenous/administration & dosage* ; Graft Survival/immunology* ; Humans ; Animals ; Sus scrofa ; Graft Rejection/prevention & control* ; Kidney/pathology* ; Gene Editing ; Species Specificity ; Immunosuppression Therapy/methods* ; Plasma Exchange ; Brain Death ; Biopsy ; Male ; Aged

Lean six sigma (LSS) emphasizes patient demand-oriented, and continuously optimizing prolesses to achieve efficiency and standardization in medical services. Starting in 2021, a specialized children′s hospital (comprising one main campus and three branch campuses) introduced the LSS management method. Through define, measure, analyze, improve, and control, the hospital utilized tools such as questionnaire surveys, SIPOC models, and fishbone diagrams to identify pain points in the building of multi-campus child-friendly hospital and develop improvement measures.To address the main issues of insufficient cross-campus collaboration, significant disparities in service quality among different campuses, unclear functional positioning of each campus, and inadequate integration with social security mechanisms, the hospital implemented a " homogeneity-differentiation-coordination" management mode. The hospital implemented unified diagnosis and treatment standards and clinical pathways, carried out remote consultations and expert rotations, completed mutual recognition of examination and testing results, optimized child friendly labeling and child friendly environment, and built a " hospital-to-hospitals, hospital to medical schools, and hospital to community health centers" linkage platform, etc., to promote the standardization of diagnosis and treatment processes, clear functional positioning of the hospital area, and efficient resource allocation. Through practice, the outpatient appointment rate and patient satisfaction rate in the main hospital had increased from 86.72% and 98.64% in January December 2021 to 91.87% and 99.72% in January December 2024, respectively; The patient waiting time had been shortened from 26.54 minutes to 21.94 minutes, and the efficiency of medical treatment and service experience had been significantly improved. As of 2024, mutual recognition of 214 inspection and testing items had been achieved cross hospital campuses, forming a collaborative pattern of " main hospital leading, campuses support, and resource complementarity", and significantly improving the level of collaboration and child friendly connotation among multi-campus. This practice explored the integration path of multi-campus collaborative governance and child-friendly services, which could provide reference and inspiration for the similar hospitals.

AIM:To investigate the effects of Nrf1 on neuronal apoptosis treated by oxygen-glucose deprivation/reperfusion and the mechanism.METHODS:Single-cell sequencing data was ana-lyzed by GEO database,and the correlation of Nrf1 expression with apoptotic pathways evaluated based on GSVA package calculations.PC12 cells and primary neurons were divided into the Normal group,the OGD/R group,the OGD/R+siRNA-NC group,and the OGD/R+Nrf1-siRNA-2 group.Cell images was observed by laser scanning confocal mi-croscopy;the viability of cells were detected by MTT assay;the apoptosis of cells were detected by flow cytometry;DHE fluorescent probe to detect ROS levels,the protein expression of Nrf1,bcl-2 and Bax were detected by Western blot;and nuclear translocation was observed by laser scanning confo-cal microscope.RESULTS:The results of biosigna-ture analysis revealed that Nrf1 was mainly en-riched in the apoptotic pathway;compared with normal group,the cell body became smaller,syn-apse broke,cells clustered in PC12 cells and prima-ry neurons with OGD/R treated,and the vitality of PC12 cells and neuronal were decreased significant-ly(P＜0.01);ROS levels were significantly higher(P＜0.01),the expressions of Nrf1 and Bax were in-creased significantly,and the expression of bcl-2 was decreased significantly(P＜0.05).Compared with the OGD/R group,there was no significant dif-ference in the siRNA-NC group;compared with the siRNA-NC group,the viability of cells was de-creased significantly(P＜0.01);ROS levels were sig-nificantly increased(P＜0.01),the expressions of Nrf1 and Bax were increased markedly,and the ex-pressions of bcl-2 was decreased significantly(P＜0.05)in Nrf1-siRNA-2 group.CONCLUSION:Nrf1 at-tenuates neuronal injury caused by oxygen glucose deprivation/reperfusion via inhibiting apoptosis.

The scientific research and innovation capabilities of medical students are intrinsically linked to the sustained and high-quality development of national healthcare initiatives.Cultivating outstanding medi-cal students with independent scientific capabilities and innovative consciousness is a critical component in the education and training of high-level medical professionals.Our investigation revealed that within the imperfections of the cultivating model,some faculty and students at medical schools have an insufficient understanding of scientific research and innovation and lack motivation for engaging in such activities,which hinder the progression of scientific research activities.Consequently,we initiated a teaching practice and exploratory study on the"tutorial system"aimed at fostering medical students'scientific research and innovation abilities.Based on the principle of"research informing teaching,teaching and research advan-cing together,"this study implements a"tutorial system"coordinated by tutors,supplemented by graduate and undergraduate student mentors,to cultivate innovative thinking,stimulate interest in scientific re-search,and enhance practical and research skills among medical students.Through collaborative efforts within"scientific research innovation teams,"various educational methods—including preliminary re-search,in-class and extracurricular activities,intra-group and inter-group interactions,and theoretical and practical applications—are employed to improve and strengthen the cultivation of medical students'scientif-ic research and innovation abilities.This study aims to provide valuable references for optimizing medical education management systems and enhancing the quality of medical student training.

The scientific research and innovation capabilities of medical students are intrinsically linked to the sustained and high-quality development of national healthcare initiatives.Cultivating outstanding medi-cal students with independent scientific capabilities and innovative consciousness is a critical component in the education and training of high-level medical professionals.Our investigation revealed that within the imperfections of the cultivating model,some faculty and students at medical schools have an insufficient understanding of scientific research and innovation and lack motivation for engaging in such activities,which hinder the progression of scientific research activities.Consequently,we initiated a teaching practice and exploratory study on the"tutorial system"aimed at fostering medical students'scientific research and innovation abilities.Based on the principle of"research informing teaching,teaching and research advan-cing together,"this study implements a"tutorial system"coordinated by tutors,supplemented by graduate and undergraduate student mentors,to cultivate innovative thinking,stimulate interest in scientific re-search,and enhance practical and research skills among medical students.Through collaborative efforts within"scientific research innovation teams,"various educational methods—including preliminary re-search,in-class and extracurricular activities,intra-group and inter-group interactions,and theoretical and practical applications—are employed to improve and strengthen the cultivation of medical students'scientif-ic research and innovation abilities.This study aims to provide valuable references for optimizing medical education management systems and enhancing the quality of medical student training.

OBJECTIVE To analyze a strain of multidrug-resistant Pseudomonas fulva by whole genome sequencing,investigate the genomic characteristics and analyze the significance in phyletic evolution.METHODS A strain of P.fulva,NY4814,was isolated from the Chinese PLA General Hospital in 2014.The genome sequence data of the strain were obtained after the purification,preservation and whole genome sequencing.The specie of the strain was identified by comparing with average nucleotide identity(ANI);the minimum inhibitory concentra-tions(MIC)of the strains were determined by VITEK2 system.All of the data regarding to the genomic se-quences of P.fulva were downloaded from RefSeq database of National Center of Biotechnology Information(NCBI)to construct the phylogenetic tree.RESULTS The P.fulva NY4814 was resistant to carbapenems and quinolones.The chromosome carried a newly discovered Tn7675 unit transposon,which mediated resistance to aminoglycosides and chloramphenicol.Simultaneously,the plasmid pNY4814-IMP drove the wide dissemination of the blaIMP resistance gene across Pseudomonas species via a highly conserved conjugative and transfer mechanism,and the Tn6485i unit transposon carried by the chromosome mediated the resistance to β-lactams.CONCLUSIONS As one of the potential carriers for the transmission of carbapenems resistance genes and other types of drug re-sistance genes,the P.fulva leads to the infection as a seldom opportunistic pathogen.The genetic structure of NY4814 and its association with genetic evolution of the species are observed in the study,which intensify the un-derstanding of the species and provide theoretical bases for prevention and monitoring of bacterial infections.

OBJECTIVE To analyze a strain of multidrug-resistant Pseudomonas fulva by whole genome sequencing,investigate the genomic characteristics and analyze the significance in phyletic evolution.METHODS A strain of P.fulva,NY4814,was isolated from the Chinese PLA General Hospital in 2014.The genome sequence data of the strain were obtained after the purification,preservation and whole genome sequencing.The specie of the strain was identified by comparing with average nucleotide identity(ANI);the minimum inhibitory concentra-tions(MIC)of the strains were determined by VITEK2 system.All of the data regarding to the genomic se-quences of P.fulva were downloaded from RefSeq database of National Center of Biotechnology Information(NCBI)to construct the phylogenetic tree.RESULTS The P.fulva NY4814 was resistant to carbapenems and quinolones.The chromosome carried a newly discovered Tn7675 unit transposon,which mediated resistance to aminoglycosides and chloramphenicol.Simultaneously,the plasmid pNY4814-IMP drove the wide dissemination of the blaIMP resistance gene across Pseudomonas species via a highly conserved conjugative and transfer mechanism,and the Tn6485i unit transposon carried by the chromosome mediated the resistance to β-lactams.CONCLUSIONS As one of the potential carriers for the transmission of carbapenems resistance genes and other types of drug re-sistance genes,the P.fulva leads to the infection as a seldom opportunistic pathogen.The genetic structure of NY4814 and its association with genetic evolution of the species are observed in the study,which intensify the un-derstanding of the species and provide theoretical bases for prevention and monitoring of bacterial infections.