Objective To explore the role and related mechanism of neutrophil membrane-coated poly(lactic-co-glycolic acid) (PLGA) nanoparticles (Neu-NP) in cardiac repair after acute myocardial ischemia-reperfusion (MI/R) injury in mice. Methods The male C57 mouse model of acute MI/R injury was established and randomly divided into three groups: PBS control group (injection of 200 μL PBS), NP treatment group (injection of 0.5 mg/mL NP 200 μL), and Neu-NP treatment group (injection of 0.5 mg/mL Neu-NP 200 μL). Neutrophil membranes were extracted and fused with PLGA nanoparticles to construct biomimetic Neu-NP. The in vivo homing ability of Neu-NP was assessed using ex vivo imaging technology in the MI/R injury model, and the expression levels of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in the myocardium were measured using enzyme linked immunosorbent assay one day and three days after administration. Echocardiography was used to determine cardiac function indicators of MI/R injured mice 28 days post-administration. Immunofluorescence staining was used to observe angiogenesis repair and inflammatory cell infiltration in mouse heart tissue. Results Neu-NP, engineered by integrating neutrophil membranes with nanoparticles, inherited surface receptors (TNF-αR and IL-6R) and functioned as decoys for inflammatory targeting. Compared with the PBS control group and NP treatment group, the secretion levels of TNF-α and IL-6 in the damaged myocardium of the Neu-NP treatment group were significantly decreased one and three days after administration (P＜0.05); 28 days after administration, the cardiac ejection fraction in the Neu-NP treatment group was significantly higher than that in the other two groups (P＜0.05). Immunofluorescence staining indicated a significant increase in the proportion of angiogenesis in the myocardial infarction area and a significant reduction in inflammation cell infiltration (P＜0.05). Conclusions Neu-NP plays an important role in cardiac tissue repair after MI/R injury by alleviating inflammatory factors in the damaged area and promoting angiogenesis.

Objective To explore the safety and effects of alpha-lipoic acid (ALA) in patients with ischemic heart failure (IHF). Methods A randomized, double-blind, placebo-controlled trial was designed (ClinicalTrial.gov registration number NCT03491969). From January 2019 to January 2023, 300 patients with IHF were enrolled in four medical centers in China, and were randomly assigned at a 1∶1 ratio to receive ALA (600 mg daily) or placebo on top of standard care for 24 months. The primary outcome was the composite outcome of hospitalization for heart failure (HF) or all-cause mortality events. The second outcome included non-fatal myocardial infarction (MI), non-fatal stroke, changes of left ventricular ejection fraction (LVEF) and 6-minute walking distance (6MWD) from baseline to 24 months after randomization. Results Finally, 138 patients of the ALA group and 139 patients of the placebo group attained the primary outcome. Hospitalization for HF or all-cause mortality events occurred in 32 patients (23.2%) of the ALA group and in 40 patients (28.8%) of the placebo group (HR＝0.753, 95%CI 0.473-1.198, P＝0.231; Figure 1A-1C). The absolute risk reduction (ARR) was 5.6%, the relative risk reduction (RRR) associated with ALA therapy was approximately 19.4% compared to placebo, corresponding to a number needed to treat (NNT) of 18 patients to prevent one event. In the secondary outcome analysis, the composite outcome of the major adverse cardiovascular events (MACE) including the hospitalization for HF, all-cause mortality events, non-fatal MI or non-fatal stroke occurred in 35 patients (25.4%) in the ALA group and 47 patients (33.8%) in the placebo group (HR＝0.685, 95%CI 0.442-1.062, P＝0.091; Figure 1D). Moreover, greater improvement in LVEF (β＝3.20, 95%CI 1.14-5.23, P＝0.002) and 6MWD (β＝31.7, 95%CI 8.3-54.7, P＝0.008) from baseline to 24 months after randomization were observed in the ALA group as compared to the placebo group. There were no differences in adverse events between the study groups. Conclusions These results show potential long-term beneficial effects of adding ALA to IHF patients. ALA could significantly improve LVEF and 6MWD compared to the placebo group in IHF patients.

Geniposidic acid(GA), a natural iridoid, exists in the roots, stems, leaves, flowers, bark, fruits, and seeds of medicinal plants of Rubiaceae, Eucommiaceae, and Plantaginaceae. Modern pharmacological studies have revealed that GA has multiple pharmacological activities, including organ-protective, anti-inflammatory, antioxidative, anti-osteoporosis, anti-neurodegenerative, and anti-cardiovascular effects. GA can enhance cell/organism defenses by upregulating key anti-inflammatory and antioxidant cytokines, while downregulating key node proteins in pro-inflammatory signaling pathways such as AhR and TLR4/MyD88, thereby exerting pharmacological effects such as organ protection. Pharmacokinetic investigations have suggested that after oral administration, GA can be distributed in multiple organs(kidney, liver, heart, spleen, lung, etc.). In addition, the pharmacokinetic behavior of GA could be significantly altered under disease conditions, as demonstrated by a marked increase in systematic exposure. This article comprehensively summarizes the reported pharmacological activities and mechanisms and systematically analyzes the pharmacokinetic characteristics and key parameters of GA, with the aim of providing a theoretical basis and scientific reference for the precise clinical application of GA-related Chinese patent medicines, as well as for the investigation and development of innovative drugs based on GA.
Humans ; Drugs, Chinese Herbal/chemistry* ; Animals ; Iridoid Glucosides/chemistry* ; Plants, Medicinal/chemistry* ; Anti-Inflammatory Agents/pharmacology*

Cervical spine health issues not only seriously affect patients' quality of life but also impose a heavy burden on the social healthcare system. Existing guidelines lack sufficient clinical guidance on lifestyle and work habits, such as exercise, posture, daily routine, and diet, making it difficult to meet practical needs. To address this, relying on the China Association of Chinese Medicine, Wangjing Hospital of China Academy of Chinese Medical Sciences took the lead and joined hands with more than ten institutions to form a multidisciplinary guideline development group. For the first time, the group developed the Guidelines for Cervical Spine Health Intervention based on evidence-based medicine methods, strictly following the standardized procedures outlined in the World Health Organization Handbook for Guideline Development and the Guiding Principles for the Formulation/Revision of Clinical Practice Guidelines in China (2022 Edition). This proposal systematically explains the methods and steps for developing the guideline, aiming to make the guideline development process scientific, standardized, and transparent.
Humans ; Practice Guidelines as Topic/standards* ; Cervical Vertebrae ; China

OBJECTIVES: To study clinical manifestations and gene mutation features of neonates with centronuclear myopathy. METHODS: A retrospective analysis was conducted on the medical data of 5 neonates with centronuclear myopathy diagnosed in the Neonatal Intensive Care Unit of Children's Hospital, Zhejiang University School of Medicine from January 2020 to August 2024. The data included gender, gestational age, birth weight, Apgar score, clinical manifestations, creatine kinase level, electromyography, genetic testing results and the outcomes of the infants. RESULTS: All 5 male neonates had a history of postpartum asphyxia and resuscitation. They all presented with hypotonia, myasthenia, and respiratory failure; two neonates also had swallowing dysfunction. Of the five neonates, three had normal creatine kinase levels, while two had slightly elevated levels. Electromyography was performed for three neonates, among whom two had myogenic damage. MTM1 gene mutations were identified by genetic testing in all five neonates, including two nonsense mutations and three missense mutations, among which one variant had not been previously reported. Four mutations were inherited from the mother, and the other one was a de novo mutation. The five neonates showed no clinical improvement following treatment, failed weaning from mechanical ventilation, and ultimately died after withdrawal of life-sustaining therapy. CONCLUSIONS Centronuclear myopathy caused by MTM1 gene mutation often has a severe phenotype and a poor prognosis, and it should be considered for neonates with hypotonia and myasthenia after birth. Genetic testing should be performed as soon as possible.
Humans ; Myopathies, Structural, Congenital/genetics* ; Male ; Infant, Newborn ; Retrospective Studies ; Mutation ; Female ; Protein Tyrosine Phosphatases, Non-Receptor/genetics*

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

Cemental tear is a rare and indetectable condition unless obvious clinical signs present with the involvement of surrounding periodontal and periapical tissues. Due to its clinical manifestations similar to common dental issues, such as vertical root fracture, primary endodontic diseases, and periodontal diseases, as well as the low awareness of cemental tear for clinicians, misdiagnosis often occurs. The critical principle for cemental tear treatment is to remove torn fragments, and overlooking fragments leads to futile therapy, which could deteriorate the conditions of the affected teeth. Therefore, accurate diagnosis and subsequent appropriate interventions are vital for managing cemental tear. Novel diagnostic tools, including cone-beam computed tomography (CBCT), microscopes, and enamel matrix derivatives, have improved early detection and management, enhancing tooth retention. The implementation of standardized diagnostic criteria and treatment protocols, combined with improved clinical awareness among dental professionals, serves to mitigate risks of diagnostic errors and suboptimal therapeutic interventions. This expert consensus reviewed the epidemiology, pathogenesis, potential predisposing factors, clinical manifestations, diagnosis, differential diagnosis, treatment, and prognosis of cemental tear, aiming to provide a clinical guideline and facilitate clinicians to have a better understanding of cemental tear.
Humans ; Dental Cementum/injuries* ; Consensus ; Diagnosis, Differential ; Cone-Beam Computed Tomography ; Tooth Fractures/therapy*

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

Background and objective Current studies suggest that for early-stage lung cancers with a component of ground-glass opacity measuring ≤2 cm,sublobar resection is suitable if it ensures adequate margins.However,lobectomy may be necessary for some cases to achieve this.The aim of this study was to explore the impact of size and depth on surgical techniques for wedge resection,segmentectomy,and lobectomy in early-stage lung cancer ≤2 cm,and to determine methods for ensuring a safe resection margin during sublobar resections.Methods Clinical data from 385 patients with early-stage lung can-cer ≤2 cm,who underwent lung resection in 2022,were subject to a retrospective analysis,covering three types of procedures:wedge resection,segmentectomy and lobectomy.The depth indicator as the OA value,which is the shortest distance from the inner edge of a pulmonary nodule to the opening of the corresponding bronchus,and the AB value,which is the distance from the inner edge of the nodule to the pleura,were measured.For cases undergoing lobectomy and segmentectomy,three-dimensional computed tomography bronchography and angiography(3D-CTBA)was performed to statistically determine the number of subsegments required for segmentectomy.The cutting margin width for wedge resection and segmentectomy was recorded,as well as the specific subsegments and their quantities removed during lung segmentectomy were documented.Results In wedge resection,segmentectomy,and lobectomy,the sizes of pulmonary nodules were(1.08±0.29)cm,(1.31±0.34)cm and(1.50±0.35)cm,respectively,while the depth of the nodules(OA values)was 6.05(5.26,6.85)cm,4.43(3.27,5.43)cm and 3.04(1.80,4.18)cm for each procedure,showing a progressive increasing trend(P＜0.001).The median resec-tion margin width obtained from segmentectomy was 2.50(1.50,3.00)cm,significantly greater than the 1.50(1.15,2.00)cm from wedge resection(P＜0.001).In wedge resections,cases where AB value＞2 cm demonstrated a higher proportion of cases with resection margins less than 2 cm compared to those with margins greater than 2 cm(29.03％vs 12.90％,P=0.019).When utilizing the size of the nodule as the criterion for resection margin,the instances with AB value＞2 cm continued to show a higher proportion in the ratio of margin distance to tumor size less than 1(37.50％vs 17.39％,P=0.009).The median number of subsegments for segmentectomy was three,whereas lobectomy cases requiring segmentectomy involved five subsegments(P＜0.001).Conclusion The selection of the surgical approach for lung resection is influenced by both the size and depth of pulmonary nodules.This study first confirms that larger portions of lung tissue must be removed for nodules that are deeper and larger to achieve a safe margin.A distance of ≤2 cm from the inner edge of the pulmonary nodule to the nearest pleura may be the ideal indication for performing wedge resection.

Objective:To develop and verify a nomogram to predict disease-free survival(DFS)and overall survival(OS)for patients undergoing cervical cancer surgery,which may provide reference for evaluating the prognosis of cervical cancer patients undergoing surgery.Methods:The clinical,pathological and follow-up data of patients who underwent radical operation for cervical cancer in Xijing Hospital,Air Force Medical University from March 2013 to October 2018 were analyzed retrospectively.Based on Cox regression analysis,Bayesian Informa-tion Criterion(BIC)backward stepwise selection method and R square screening variables,Net Reclassification Index(NRI)and Integrated Discrimination Improvement(IDI)were used to compare the predictive efficiency of the model,and a nomogram with better predictive efficiency was selected.The consistency index(C-index)and the receiver operating characteristic curve(ROC)were used to test the efficiency of the nomogram.Results:A total of 950 patients with cervical cancer were enrolled in this study.The risk factors for constructing the DFS nomogram were FIGO stage(2018),parametrium invasion,invasion depth,and maximum tumor diameter.The C-index for DFS in the training cohort and the verification cohort were 0.754 and 0.720,respectively.The area under ROC of the training cohort for 1-,3-and 5-years was 0.74(95%CI 0.65-0.82),0.77(95%CI 0.71-0.83)and 0.79(95%CI0.74-0.85),and the areas under ROC of verification cohort 1-,3-and 5-years were 0.72(95%CI 0.58-0.87),0.75(95%CI 0.64-0.86)and 0.72(95%CI 0.61-0.84),respectively.The risk factors for con-structing the OS nomogram were FIGO stage(2018),histological type,LVSI,parametrium invasion,surgical mar-gin,and invasion depth.The C-index for OS in the training cohort and the verification cohort were 0.737 and 0.759,respectively.The area under ROC of the 3-and 5-year training cohort were 0.76(95%CI 0.69-0.83)and 0.78(95%CI 0.72-0.84),and the areas under ROC of verification cohort 3-and 5-years were 0.76(95%CI 0.65-0.87)and 0.79(95%CI 0.69-0.88),respectively.Conclusions:This study is based on real-world big data to construct nomogram of DFS for 1,3,and 5 years and OS for 3,and 5 years for cervical cancer,which have ideal predictive effects and help clinical physicians correctly evaluate the prognosis of cervical cancer surgery patients.It provides strong reference basis for diagnosis,treatment,and prognosis evaluation.