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

OBJECTIVE To provide reference for improving the work efficiency of staff and promoting the discipline construction of pharmacy department. METHODS By analyzing the current situation of performance management in the pharmacy department of our hospital， the key successful factors were sorted out， strategic decoding was carried out and key performance indicators were extracted. The quarterly and annual performance appraisal forms were formulated for the departments of pharmacy warehouse， outpatient pharmacy， ward pharmacy， clinical pharmacy department， prescription examination center， laboratory and other departments； the performance management information platform was built. The work efficiency and output of each department were compared half a year before and after the implementation of the performance management plan. RESULTS After the implementation of the program， the average queuing time for drug collection in the outpatient department was shortened from 5 minutes to 3 minutes， the average number of dispensing infusion bags per hour in the pharmacy intravenous admixture services increased from 50 bags to 60 bags， and antibacterial use density of the hospital decreased from 42.7 DDD（defined daily doses） to 40.2 DDD. The number of academic papers published had increased from 8 to 10， and the satisfaction of clinical departments with ward pharmacies increased from 85% to 95%. CONCLUSIONS The performance management system has been successfully established in pharmacy department of our hospital， which can improve the enthusiasm of pharmacists， reflect the value of pharmaceutical care， and promote the discipline construction of pharmacy.

Objective To investigate the expression of centromere protein U(CENPU)in the intestinal tissues of patients with colon cancer,and to analyze the effect of CENPU expression level on the prognosis of patients with colon cancer combined with bioinformatics.Methods Firstly,the expression of CENPU in cancer tissues and normal tissues of colon cancer patients was analyzed by the expression of CENPU in tissues was further verified by real-time quantitative real time polymerase chain reaction(qRT-PCR),Western blot(WB)and immunohistochemistry(IHC).Combined with clinical data,univariate and multivariate Cox regression are used to analyze the correlation between CENPU expression and clinical case parameters of colon cancer patients.Then,the predictive effect of CENPU expression on the prognosis of colon cancer patients are explored by drawing receiver operating characteristic(ROC)curve and Kaplan-Meier survival curve.Finally,the possible molecular mechanism of the effect of CENPU expression on the progression of colon cancer are analyzed by bioinformatics.Results By qRT-PCR,WB and IHC experiments,we find that compared with normal tissues,the expression of CENPU in cancer tissues of colon cancer patients is significantly increased.Cox regression analysis show that the expression of CENPU is significantly correlated with the age and TNM stage of patients,and is a risk factor affecting the prognosis of patients.Kaplan-Meier survival curve analysis show that colon cancer patients with high CENPU expression has significantly lower survival rates.ROC curve show that the model based on CENPU expression has a high predictive power for the prognosis of colon cancer patients area under the curve(AUC=0.832).Bioinformatics analysis show that CENPI,CENPN,CENPD,CENPK,CENPP,CENPM,CENPQ,CENPH,NDC80 and ITGB3BP have significant interaction with CENPU gene.CENPU is involved in DNA repair,MYC/TARGETS/V1 and PI3K/AKT/MTOR signaling pathways.Conclusion High expression of CENPU in cancer tissues of patients with colon cancer is significantly associated with poor prognosis of patients,suggesting that CENPU is expected to be a potential target for early diagnosis and prognosis prediction of patients with colon cancer.