Objective To investigate dynamic changes in myocardial protein phosphorylation during the acute phase of myocardial infarction (MI) in mice. Methods Six 8-week-old C57BL/6J mice were randomly assigned to MI model (n＝3) or sham-operated control (n＝3) groups. Cardiac tissues were harvested 72 hours post-intervention for proteomic analysis. Phosphorylation modifications were systematically characterized using liquid chromatography-mass spectrometry (LC-MS). Bioinformatics analyses included differential phosphorylation screening, functional enrichment, hierarchical clustering, and protein-protein interaction network. Results LC-MS identified 1 921 differentially phosphorylated sites (20 tyrosine and 1 901 serine/threonine sites) across 851 proteins. Compared with controls, MI hearts exhibited significant phosphorylation upregulation at 1 545 sites and downregulation at 376 sites (P＜0.05). Conclusions This study delineates MI-associated phosphorylation dynamics, providing mechanistic insights and potential therapeutic targets for acute MI intervention.

Cognitive impairment （CI） is a clinical syndrome characterized by progressive decline in advanced cognitive functions such as memory， thinking， and judgment. Its etiology and pathogenesis are complex， and there is currently a lack of specific drug interventions. Metformin， as a first-line hypoglycemic drug for type 2 diabetes， not only lowers blood glucose levels but also improves CI. This article reviews and summarizes the pharmacological effects and mechanisms of metformin in improving Alzheimer’s disease， diabetes cognitive impairment， cognitive impairment after chemotherapy， in order to provide novel insights and approaches for the treatment of CI-related diseases. Studies have shown that the mechanism by which MET intervenes in CI mainly includes regulating β-amyloid protein and tau protein metabolism， reducing insulin resistance， inhibiting neuroinflammation， improving synaptic plasticity， improving mitochondrial dysfunction， regulating gut microbiota and lipid metabolism， etc. Future research needs to be conducted through interdisciplinary collaboration， fully integrating multiple omics data， and combining advanced technologies to further reveal their mechanisms of effect.

The cellular and molecular components of the tumor immune microenvironment (TIME) and their information exchange processes significantly influence the trends of anti-tumor immunity. In recent years, numerous studies have begun to evaluate TIME in the context of previous cancer treatment strategies. This review will systematically summarize the compositional characteristics of TIME and, based on this foundation, explore the impact of current cancer therapies on the remodeling of TIME, aiming to provide new insights for the development of innovative immune combination therapies that can convert TIME into an anti-tumor profile.
Tumor Microenvironment/immunology* ; Humans ; Neoplasms/therapy* ; Immunotherapy/methods* ; Animals

OBJECTIVE: To propose a new protocol for personalized mandibular reconstruction assisted by three-dimensional (3D) retrieval model based on fully connected neural network (FCNN) and a database of mandibles, and to verify clinical feasibility of the protocol. METHODS: A database of mandibles of 300 normal northern Chinese Han people was established. On the basis of cephalometry, the mandible landmarks with good stability were further screened. Mandibular landmarks were selected and geometric features of the mandible were extracted. A 3D retrieval algorithm was developed, which could retrieve the mandible most similar to a given mandible from the database. A FCNN was built to train the algorithm to improve accuracy of the 3D retrieval model. Using Geomagic Control 2014 software, matching accuracy of the 3D retrieval model was based on aforementioned mandible database and algorithm. From December 2019 to March 2021, a total of 5 patients underwent personalized mandibular reconstruction assisted by a 3D retrieval model based on mandible database and FCNN in the Department of Oral and Maxillofacial Surgery, Peking University School and Hospital of Stomatology. The most similar mandible was retrieved from mandible database through 3D retrieval algorithm. It was used to restore the premorbid morphology of defect area and guide mandibular reconstruction. For the 5 patients, mandible was reconstructed with iliac flap. Virtual surgical plan was transformed using individual surgical guides. RESULTS: Through screening, mandibular landmarks with high reproducibility and stability were identified and composed of mandibular landmarker protocols. After training, the average deviation between most similar mandible retrieved from the 300-case mandible database through 3D retrieval model based on FCNN and given mandible was (1.77±0.44) mm. And the root-mean-square deviation between the most similar mandible retrieved from the database and given mandible was (2.58±0.86) mm. The mandibular reconstruction surgery was successful in all the 5 patients. Their facial symmetry and occlusion were restored. All the patients were satisfied with postoperative appearance. The mean deviation between postoperative mandible and preoperative design was (0.98±0.17) mm. The area with a deviation ≤1 mm accounted for 61.34%±14. 13%, ≤2 mm accounted for 83.82%±7.35%, and ≤3 mm accounted for 93.94%± 2.87%. CONCLUSION The personalized mandibular reconstruction assisted by 3D retrieval model based on the 300-case mandible database and FCNN is feasible clinically.
Humans ; Neural Networks, Computer ; Mandibular Reconstruction/methods* ; Mandible/diagnostic imaging* ; Imaging, Three-Dimensional/methods* ; Adult ; Databases, Factual ; Female ; Male ; Algorithms ; Middle Aged ; Cephalometry

OBJECTIVES: The 24-hour movement behaviors, comprising physical activity, sedentary behavior, and sleep, are crucial factors affecting children's mental health. This study aims to explore the longitudinal association between 24-hour movement behaviors and psychological well-being in overweight and obese children, providing empirical evidence for mental health promotion in this population. METHODS: A total of 445 overweight and obese children were recruited via stratified cluster random sampling from a provincial capital city in China and followed up for one year. Measures included objectively assessed physical activity and sleep duration using triaxial accelerometers (ActiGraph GT3X+), parent-reported sedentary screen-based time (SST), and self-reported psychological well-being. RESULTS: After one year, the proportion of children meeting all 3 movement guidelines increased from 10.11% to 11.68%, while those meeting none increased from 11.24% to 15.06%. After adjusting for relevant covariates, children who met individual guidelines for moderate-to-vigorous physical activity (MVPA) (β=0.377, 95% CI 0.209 to 0.545), sleep (β=0.187, 95% CI 0.042 to 0.332), or guideline combinations of MVPA+SST (β=0.545, 95% CI 0.377 to 0.713) and MVPA+sleep (β=0.602, 95% CI 0.449 to 0.755) showed significant improvements in psychological well-being after one year. Additionally, an increase in the number of guidelines met was significantly associated with improved well-being (β=0.113, 95% CI 0.011 to 0.214). CONCLUSIONS Adherence to any single movement guideline, especially MVPA or sleep, and combinations such as MVPA+SST or MVPA+sleep is significantly associated with enhanced psychological well-being in overweight and obese children. Integrated behaviors may be an effective strategy to improve mental well-being in this population.
Humans ; Child ; Exercise/psychology* ; Sleep ; Sedentary Behavior ; Female ; Male ; Pediatric Obesity/psychology* ; Overweight/psychology* ; Mental Health ; China ; Accelerometry ; Psychological Well-Being

Ovulatory dysfunction (OD) is one of the main causes of infertility in women of childbearing age, which not only affects their reproductive ability, but also physical and mental health. Traditional treatment strategies have limited efficacies, and the emergence of biomedicines provides a promising alternative solution via the strategies of combining engineered design with modern advanced technology. This review explores the pathophysiological characteristics and related induction mechanisms of OD, and evaluates the current cutting-edge advances in its treatments. It emphasizes the potentials of biomedicines strategies such as hydrogels, nanoparticles and extracellular vesicles in improving therapeutic precision and efficacy. By mimicking natural physiological processes, and achieving controlled drug release, these advanced drug carriers are expected to address the challenges in ovarian microenvironment reprogramming, tissue repair, and metabolic and immune regulation. Despite the promising progress, there are still challenges in terms of biomedical complexity, differences between animal models and human physiology, and the demand for intelligent drug carriers in the therapy of OD. Future researches are mainly dedicated to developing precise personalized biomedicines in OD therapy through interdisciplinary collaboration, promoting the development of reproductive regenerative medicine.

Cognitive impairment is a major public health challenge facing global aging societies， and currently lacks effective treatment measures. Herb pair， characterized by their rigorous compatibility and synergistic effects， demonstrate unique advantages in clinical practice. Acorus tatarinowii-Polygala tenuifolia is a classic herbal pair for treating cognitive impairment， widely utilized in various traditional Chinese medicine formulations， such as Kaixin san， Shenghui tang， and Yuanzhi san. This article summarizes the pharmacological mechanisms of A. tatarinowii， P. tenuifolia and their compatible compound prescriptions in ameliorating cognitive impairment. It is found that they can exert effects in ameliorating cognitive impairment through mechanisms such as reducing amyloid β-protein deposition and inhibiting excessive phosphorylation of Tau protein， suppressing inflammatory responses， alleviating oxidative stress， protecting neurons and regulating neurotransmitters， modulating the structure and function of the blood- brain barrier， and regulating autophagy. Subsequently， in-depth analysis can be conducted on the active ingredients of A. tatarinowii- P. tenuifolia herb pair that ameliorate cognitive impairment， along with the addition of relevant clinical trials for verification. This will provide theoretical foundations and research approaches for the treatment of cognitive impairment using traditional Chinese medicine.

Objective: To investigate the current status and influencing factors of quality of life among HIV/AIDS cases, so as to provide the basis for improving HIV/AIDS cases quality of life. Methods: From March to July 2024, HIV/AIDS cases under follow-up management at various community health service centers in Jinshan District, Shanghai Municipality, were selected as the survey subjects using a convenience sampling method. Demographic information and receiving antiretroviral therapy (ART) were collected through questionnaire surveys. Quality of life was assessed using the Chinese version of the World Health Organization Quality of Life Questionnaire for HIV brief version. A multiple linear regression model was employed to analyze the factors affecting quality of life. Results: A total of 179 HIV/AIDS cases were investigated, including 150 males (83.80%) and 29 females (16.20%), with a mean age of (47.00±12.90) years. The subjective self-evaluation score for the quality of life among HIV/AIDS cases was (13.87±2.84) points. The scores in the domains of physical, psychological, independence, social relationship, environment, and spiritual support/religion/personal beliefs were (14.77±2.64) (13.57±2.04) (13.86±2.04) (12.99±2.26) (13.58±1.98) (14.59±3.05) points, respectively. Multiple linear regression analysis revealed statistically significant associations (all P<0.05) between the following factors and quality of life domain scores: educational level (college degree or above, β' =0.162) and receiving ART (β' =-0.197) were associated with the subjective self-evaluation domain score; educational level (college degree or above, β' =0.186) and receiving ART (β' =-0.299) were associated with physical domain score; receiving ART (β' =-0.263) and symptoms related to sexually transmitted diseases (β' =-0.243) were associated with psychological domain score; occupation (retirees, β' =-0.191) and symptoms related to sexually transmitted diseases (β' =-0.220) were correlated with the independence domain score; annual household income per capita (≥30 000 yuan, β' =0.281) and receiving ART (β' =-0.299) were correlated with the social relationship domain score; educational level (college degree or above, β' =0.206) and receiving ART (β' =-0.285) were correlated with the environment domain score; and receiving ART (β' =-0.492) and duration since HIV confirmation (3 to <6 years, β' =0.233; ≥6 years, β' =0.161) were correlated with the spiritual support/religion/personal beliefs domain score. Conclusions The overall quality of life among HIV/AIDS cases in Jinshan District is relatively good, but the domains of psychological, independence, and social relationship were still room for improvement. It is mainly influenced by factors such as occupation, educational level, annual household income per capita, receiving ART, symptoms related to sexually transmitted diseases, and duration since HIV confirmation.

Abstract Ring finger protein 183(RNF183) is an E3 ubiquitin ligase that catalyzes the covalent attachment of ubiquitin molecules to substrate proteins. RNF183 is expressed in tissues such as kidney and testis, and it is mainly localized to the endoplasmic reticulum, Golgi apparatus, and lysosomes in cells. As one of the components of the endoplasmic reticulum membrane, it participates in the endoplasmic reticulum stress-responsive pathway that affects cellular and protein ubiquitination. In recent years, the study of E3 ubiquitin ligase member-RNF183 with various diseases such as colorectal cancer, endometrial cancer and bladder cancer has gradually increased. In this review, the role of RNF183 in colorectal cancer, inflammatory bowel disease and other diseases, as well as biological functions such as endoplasmic reticulum stress are summarized, aiming to provide reference ideas for the study of related diseases.

Objective The potential mechanism of hepatotoxicity induced by rhubarb was preliminarily explored by network pharmacology and verified by cell experiments.Methods Based on network pharmacology,component collection and target prediction are carried out through multiple databases.PPI network construction,GO enrichment analysis and KEGG pathway analysis were combined with software to systematically predict the mechanism of hepatotoxicity induced by rhubarb.The pathway information predicted by network pharmacology was verified by primary hepatocyte experiments and Western blot experiments.Results The results of network pharmacology showed that RH was the main component of hepatotoxicity induced by rhubarb.Seventeen core targets of hepatotoxicity induced by rhubarb were obtained.KEGG results suggested that DNA damage and apoptosis were one of the key mechanisms of hepatotoxicity induced by rhubarb.The results of primary hepatocytes and Western blot showed that RH could inhibit the viability of primary hepatocytes in a time-dose dependent manner.ABT and SFP can significantly reduce the toxicity of RH on primary liver cells in mice,and RFP can increase the toxicity of RH to mouse primary liver cells.Upregulation of γ-H2AX and PARP-1 protein in primary liver cells of mice after treatment with different concentrations of RH.Conclusion RH in rhubarb can significantly inhibit the viability of mouse primary hepatocytes,and its toxicity to mouse primary hepatocytes is mainly caused by the metabolic activation of RH by CYP 2C9.RH can activate PARP-1 protein,phosphorylate H2AX,induce DNA damage and apoptosis in mouse primary hepatocytes.