OBJECTIVE To investigate the apoptosis-inducing effect of esculetin （Esc） on acute myeloid leukemia （AML） HL-60 cells by regulating the protein kinase B （AKT）/S-phase kinase-associated protein 2 （SKP2）/MutT homolog 1 （MTH1） pathway. METHODS AML HL-60 cells were randomly divided into control group （routine culture）， Esc low-concentration group （L-Esc group， 25 μmol/L Esc）， Esc medium-concentration group （M-Esc group， 50 μmol/L Esc）， Esc high-concentration group （H-Esc group， 100 μmol/L Esc）， and high-concentration of Esc+ SC79 （AKT agonist） group （100 μmol/L Esc+5 μmol/L SC79）. Cell proliferation in each group was detected by MTT assay and colony formation assay. The level of reactive oxygen species （ROS） in cells was measured by using the CM-H2DCFDA fluorescent probe. Cell apoptosis was analyzed by flow cytometry. Western blot assay was performed to detect the expression levels of apoptosis-related proteins [B-cell lymphoma 2 （Bcl-2）， Bcl-2-associated X protein （Bax）， cleaved caspase-3]， AKT/SKP2/MTH1 pathway-related proteins （p-AKT， AKT， SKP2， MTH1）， along with the upstream and downstream proteins of AKT phosphatidylinositol 3-kinase （PI3K）， cyclin-dependent kinase inhibitor 1 （P21） and cyclin-dependent kinase inhibitor 1B （P27）. RESULTS Compared with control group， the cell viability， colony number， and the phosphorylation levels of AKT and PI3K proteins as well as protein expressions of SKP2， MTH1 and Bcl-2 were significantly decreased （P＜0.05）， while ROS level， apoptosis rate， and the expression levels of Bax， cleaved caspase-3， P21 and P27 proteins were significantly increased （P＜0.05）. Moreover， the effects of Esc exhibited concentration-dependence （P＜0.05）. Compared with H-Esc group， above indexes of high-concentration of Esc+ SC79 group were reversed significantly （P＜0.05）. CONCLUSIONS Esc may promote massive ROS production and induce activation of apoptosis in HL-60 cells by inhibiting the AKT/SKP2/MTH1 pathway， thus inhibiting the proliferation of HL-60 cells.

Purpose: The aim of this study is to determine the impact of solute carrier family 3 member 2 (SLC3A2) on the malignant phenotype of gliomas and its role in regulating ferroptosis sensitivity. Materials and Methods: The malignant phenotype of glioma was assessed by cell proliferation assay, colony formation assay, EdU assay, wound healing, and Transwell experiments. We further validated the impact of reduced SLC3A2 expression on the sensitivity to ferroptosis in glioma cells through Cell Counting Kit-8 assays, flow cytometry, western blotting, and transmission electron microscopy. Western blot was used to explore how SLC3A2 affects glioma sensitivity to ferroptosis through the AKT/NF-E2-related factor 2 (NRF2)/glutathione peroxidase 4 (GPX4) axis. By establishing a subcutaneous xenograft tumor model in BALB/c-nude mice, we investigated the growth of tumors following the knockout of SLC3A2 in glioma cells. Results: Downregulation of SLC3A2 suppressed the malignant phenotype of glioma by blocking the cell cycle and epithelial-mesenchymal transition processes. On the other hand, loss of SLC3A2 not only downregulated SLC7A11 but also prevented the activation of the AKT/NRF2/GPX4 axis. These lead to increased accumulation of reactive oxygen species and lipid peroxides, ultimately enhancing the susceptibility of glioma to ferroptosis. Conclusion Our findings suggest that SLC3A2 is an oncogene in gliomas, promoting their occurrence and development. It plays a critical role in ferroptosis resistance through the AKT/NRF2/GPX4 axis.

With the growing emphasis on maternal and child oral health, the significance of managing oral health across preconception, pregnancy, and infancy stages has become increasingly apparent. Oral health challenges extend beyond affecting maternal well-being, exerting profound influences on fetal and neonatal oral development as well as immune system maturation. This expert consensus paper, developed using a modified Delphi method, reviews current research and provides recommendations on maternal and child oral health management. It underscores the critical role of comprehensive oral assessments prior to conception, diligent oral health management throughout pregnancy, and meticulous oral hygiene practices during infancy. Effective strategies should be seamlessly integrated across the life course, encompassing preconception oral assessments, systematic dental care during pregnancy, and routine infant oral hygiene. Collaborative efforts among pediatric dentists, maternal and child health workers, and obstetricians are crucial to improving outcomes and fostering clinical research, contributing to evidence-based health management strategies.
Humans ; Pregnancy ; Female ; Infant ; Consensus ; Mouth Diseases/therapy* ; Pregnancy Complications/therapy* ; Oral Health ; Infant, Newborn ; Delphi Technique ; Oral Hygiene

Objective To investigate the factors influencing the efficacy of intravesical Bacille Calmette-Guérin(BCG)instillation after transurethral resection of bladder tumor(TURBT)in patients with intermediate-and high-risk non-muscle invasive bladder cancer(NMIBC),and to construct a prediction model for recurrence after BCG treatment.Methods A retrospective cohort study was conducted on the subjected patients diagnosed with intermediate-and high-risk NMIBC undergoing TURBT followed by standard BCG instillation.The 110 patients treated in Department of Urology of Army Medical Center of PLA from January 2018 to December 2023 were assigned into a training set,while the 52 patients treated at Department of Urology of General Hospital of Central Theater Command from January 2015 to December 2020 were into an external validation set.A total of 17 variables were included and analyzed.Univariate and multivariate Cox regression analyses were performed to identify factors associated with recurrence after BCG instillation,and nomograms were plotted to predict 1-year,3-year,and 5-year recurrence-free survival(RFS).Calibration curve,decision curve analysis(DCA),and receiver operating characteristic(ROC)curve analysis were conducted for internal and external validation to evaluate the predictive performance and clinical utility of the model.Results In the training set,26 patients(23.64%)experienced recurrence during the follow-up period,with a median RFS of 32.00(18.00～50.50)months.Univariate Cox regression analysis suggested that platelet count,eosinophil to lymphocyte ratio(ELR),neutrophil to lymphocyte ratio(NLR),platelet to lymphocyte ratio(PLR),systemic immune inflammation(SII)index,and neutrophil-monocyte to lymphocyte ratio(NMLR),pathological T1 stage(pT1)tumor and hemoglobin,albumin,lymphocyte,and platelet(HALP)score were potential factors influencing recurrence after BCG instillation.Multivariate Cox regression analysis identified high HALP score(HR=0.185,95%CI:0.046～0.736,P=0.017)as an independent protective factor,while high ELR(HR=3.599,95%CI:1.505～8.608,P=0.004)and pT1 stage(HR=3.240,95%CI:1.191～8.818,P=0.021)were independent risk factors for recurrence.Based on this,a nomogram prediction model was constructed.The calibration curves demonstrated good agreement between predicted and actual 1-,3-,and 5-year recurrence risks.Decision curve analysis indicated clinical utility across a wide threshold probability range.In the training set,the model showed strong predictive performance for 1-(AUC=0.842),3-(AUC=0.847),and 5-year(AUC=0.887)recurrence risks,which was further validated in the external cohort.Conclusion Higher HALP score prior to BCG instillation therapy is a protective factor against tumor recurrence,while higher ELR and pT1 stage are risk factors.Our nomogram prediction model based on HALP score,ELR and pathological T stage,can identify individuals at high risk of recurrence after BCG instillation therapy.

Objective To investigate risk factors for residual lesions after initial transurethral resection of bladder tumors(TURBT)and risk factors for tumor recurrence after second TURBT in patients with non-muscle-invasive bladder cancer(NMIBC)in order to provide reference for clinical management.Methods A case-control study design was adopted to include 120 NMIBC patients who underwent initial TURBT and then second surgery within 2～8 weeks in our department from January 2017 to January 2025.Based on the presence of residual lesions after the initial TURBT or not,the patients were divided into a residual lesion group(n=34)and a non-residual lesion group(n=86).Chi-square test and multivariate logistic regression analysis were performed to identify potential risk factors for residual lesions following the initial TURBT.Univariate and multivariate Cox regression models were used to analyze potential risk factors for tumor recurrence after the second TURBT.Results The residual lesion rate after initial TURBT was 28.33％.Chi-square test analysis revealed that tumor stage T1(Chi-square=5.756,P=0.016)and broad tumor base(Chi-square=4.331,P=0.037)were factors influencing residual lesions after initial TURBT.Multivariate logistic regression analysis identified tumor stage T1(OR=3.047,95％CI:1.128～8.226,P=0.028)as an independent risk factor for residual lesions after initial TURBT.The tumor recurrence rate after second TURBT was 17.5％.Multivariate Cox regression analysis identified tumor stage T1(OR=4.258,95％CI:1.248～14.532,P=0.021),intravesical chemotherapy instillation after second TURBT(OR=3.539,95％CI:1.284～9.752,P=0.015),history of urinary system tumors(OR=3.002,95％CI:1.145～7.873,P=0.025)and high platelet-to-lymphocyte(PLR)ratio(OR=2.798,95％CI:1.115～7.023,P=0.028)as independent risk factors for tumor recurrence after second TURBT.Conclusion Tumor stage T1 and broad tumor base are risk factors for residual lesions after initial TURBT,while tumor stage T1,intravesical chemotherapy instillation after second TURBT,history of urinary system tumors and high PLR ratio are risk factors for tumor recurrence after second TURBT.Comprehensive analysis on above 4 indicators can effectively assess the risk of tumor recurrence in NMIBC patients following second TURBT,and timely early medical intervention is beneficial for improving patient outcomes.

With the rapid development of population aging in various countries around the world,the health and elderly care industry has been paid high attention.The standardization of smart health and elderly care technology and services is particularly important.This paper firstly reviewed the policies related to healthy elderly care in China.By analyzing the industrial standards and provincial standards issued,this paper focused on the policies proposed by the Shanghai Municipal Government for the standardization of smart health and elderly care,as well as the researches on the standard system and the construction of standard families.Shanghai group standards in the field of smart health and elderly care were summarized,including the guidelines for the construction of standard systems,elderly care service platforms,community elderly cafeterias,portable health monitoring terminals,indoor sports services,and home-based elderly care safety monitoring.A series of case analyses of the standardized implementation of the above aspects were also provided.Through standardization research and practice in recent years,it has been fully demonstrated that the standard research plays an important leading role in the field of smart health and elderly care.

Hypoxia-related diseases,such as altitude sickness,acute lung injury,and heart failure,have emerged as significant public health challenges worldwide and are strongly associated with increased mortality risks.These conditions tend to cause functional impairment and structural alterations in multiple organs,primarily due to inadequate oxygen supply or the inability of tissues to utilize oxygen effectively.To elucidate the pathophysiological mechanisms underlying hypoxia-associated diseases and to explore potential therapeutic strategies,researchers have employed animal models to conduct extensive mechanistic studies and drug development trials.In this review,we provide a comprehensive overview of the methods used to construct animal models for various hypoxia-related diseases.We made a thorough evaluation of the strengths,weaknesses,limitations,and applicability of each approach.In particular,we focus on modeling strategies for key pathologies such as altitude sickness,acute lung injury,pulmonary hypertension,and heart failure,discussing their respective advantages and restrains.Furthermore,we examined the potential application of gene editing technologies in optimizing animal models,especially its role in enhancing the accuracy and reproducibility of the models.The integration of these advanced technologies holds great promise for developing animal models with improved specificity and simulation of key features of diseases,which will serve as a solid foundation for basic research,drug screening,and preclinical trials concerning hypoxia-related diseases.Herein,we present a systematic summary and future outlook of animal models for hypoxia-related diseases,ultimately providing theoretical support for developing clinical treatment strategies and improving patient outcomes.

Objective:This study introduces a novel segmented and layered thoracic laminoplasty technique for the treatment of thoracic spinal stenosis (TSS) caused by ossification of the posterior longitudinal ligament (OPLL) and ligamentum flavum (OLF). The goal is to simplify the surgical procedure, improve safety, reduce iatrogenic injuries, and validate its clinical outcomes through follow-up.Methods:A retrospective analysis was conducted on 23 patients (10 males, 13 females; mean age 58.83±12.01 years) treated at Taizhou People's Hospital Affiliated to Nanjing Medical University from January 2018 to December 2023. Transverse grooves were created at the superior and inferior vertebral pedicle levels, utilizing the intervertebral ligamentum flavum as a segmental demarcation reference. Partial removal of the distal lamina and medial of the inferior articular process was performed through a cortical window. Under direct visualization, complete removal of ossified ligamentum flavum, proximal portion of lamina, superior articular process. The treatment effect was evaluated by clinical symptoms, signs, Japanese Orthopaedic Association (JOA) score, visual analogue scale (VAS), imaging results (CT and MRI) and complications before or after surgery.Results:All 23 procedures were successfully completed with a mean operative duration of 180(150, 220) min, the surgical time for 71 segments were 67.5(53.8, 120.0) minutes and intraoperative blood loss of 200(100, 300) ml, demonstrating a low intraoperative dural tear rate of 8.70% (2/23). Postoperative imaging (CT/MRI) confirmed adequate decompression in all cases, with significant symptom improvement at final follow-up 21(9, 39) months: 47% (7/15) of patients achieved marked relief of lower limb numbness, 82% (14/17) showed substantial motor recovery, and 54% (7/13) exhibited improved gait stability. Functional outcomes revealed significant enhancements, with JOA scores increasing from 8(6, 8) preoperatively to 9(8, 10) postoperatively ( P<0.05; 43.80% improvement rate) and VAS scores decreasing from 6(5, 7) to 2(1, 4) ( P<0.05). The complications were two dural tears and one suture reaction. Conclusions:Ultrasonic osteotome-assisted segmented layered laminectomy is a safe, effective, and straightforward technique for treating thoracic spinal stenosis caused by OPLL and OLF. It offers shorter operative times, minimal complications, and significant clinical improvement, making it a promising technique for broader clinical adoption.

Objective To analyze the efficacy of vascularized lymph node transplantation(VLNT)combined with lymphatic venous anastomosis(LVA)in the treatment of secondary lower extremity lymphedema assisted by super microsurgical techniques.Methods A retrospective analysis was performed for 15 patients with secondary lower limb lymphedema who underwent VLNT+LVA surgery in the Department of Reconstructive and Reconstructive Microsurgery of Ruikang Hospital Affiliated to Guangxi University of Traditional Chinese Medicine from July 2021 to July 2023,and compared the circumference and volume of each segment of the lower limb between the preoperative and postoperative 90 days.LVA according to the results of ICG examination,3-5 parts of the lower limb were selected for"Z"shaped surgery,and the lymphatic vessels and venules were anastomosed under the microscope in the subcutaneous fat layer.VLNT confirmed and labeled the saphenous branch of the descending knee artery and its accompanying veins in the popliteal fossa,and the latissimus dorsi lymph node flap was incised,and the flap vessels were anastomosed with the saphenous branch of the descending knee artery and its accompanying veins.Postoperative observation of flap vascularization.The circumference and volume of the affected limb were measured before surgery and 90 days after surgery.Results A total of 15 patients with lower extremity lymphedema were included without serious complications.Statistical analysis showed that the circumference of all levels of the affected limb and the volume of the affected limb were improved 90 days after operation compared with those before surgery.Among them,the limb circumference and volume at each level from the highest point of the dorsum of the foot to 52 cm above the ankle improved 90 days after the operation compared with those before the operation.Conclusion LNT+LVA treatment for secondary lower extremity lymphedema can effectively control edema and improve the function of the affected limb.

Objective:This study introduces a novel segmented and layered thoracic laminoplasty technique for the treatment of thoracic spinal stenosis (TSS) caused by ossification of the posterior longitudinal ligament (OPLL) and ligamentum flavum (OLF). The goal is to simplify the surgical procedure, improve safety, reduce iatrogenic injuries, and validate its clinical outcomes through follow-up.Methods:A retrospective analysis was conducted on 23 patients (10 males, 13 females; mean age 58.83±12.01 years) treated at Taizhou People's Hospital Affiliated to Nanjing Medical University from January 2018 to December 2023. Transverse grooves were created at the superior and inferior vertebral pedicle levels, utilizing the intervertebral ligamentum flavum as a segmental demarcation reference. Partial removal of the distal lamina and medial of the inferior articular process was performed through a cortical window. Under direct visualization, complete removal of ossified ligamentum flavum, proximal portion of lamina, superior articular process. The treatment effect was evaluated by clinical symptoms, signs, Japanese Orthopaedic Association (JOA) score, visual analogue scale (VAS), imaging results (CT and MRI) and complications before or after surgery.Results:All 23 procedures were successfully completed with a mean operative duration of 180(150, 220) min, the surgical time for 71 segments were 67.5(53.8, 120.0) minutes and intraoperative blood loss of 200(100, 300) ml, demonstrating a low intraoperative dural tear rate of 8.70% (2/23). Postoperative imaging (CT/MRI) confirmed adequate decompression in all cases, with significant symptom improvement at final follow-up 21(9, 39) months: 47% (7/15) of patients achieved marked relief of lower limb numbness, 82% (14/17) showed substantial motor recovery, and 54% (7/13) exhibited improved gait stability. Functional outcomes revealed significant enhancements, with JOA scores increasing from 8(6, 8) preoperatively to 9(8, 10) postoperatively ( P<0.05; 43.80% improvement rate) and VAS scores decreasing from 6(5, 7) to 2(1, 4) ( P<0.05). The complications were two dural tears and one suture reaction. Conclusions:Ultrasonic osteotome-assisted segmented layered laminectomy is a safe, effective, and straightforward technique for treating thoracic spinal stenosis caused by OPLL and OLF. It offers shorter operative times, minimal complications, and significant clinical improvement, making it a promising technique for broader clinical adoption.