Platelets are small, anucleated cells generated by cytoplasmic fragmentation and shedding from mature megakaryocytes. Upon vascular stimulation or injury, platelets become activated and adhere to exposed vascular endothelial cells, ultimately forming thrombi to promote blood coagulation and wound healing. In recent years, increasing evidence from in-depth studies on platelet function has revealed that autophagy plays a crucial role in platelet production and functional performance. Autophagy is an intracellular process of material recycling and reuse, involving autophagosome formation, cargo degradation, and nutrient recycling, which facilitates the maintenance of homeostasis and defense against pathogen infection. Numerous studies have demonstrated that autophagy participates in the regulation of platelet production, activation, and aggregation, and is closely implicated in the pathogenesis of platelet dysfunction-related diseases such as immune thrombocytopenia. Additionally, platelet-rich plasma therapy, by modulating the autophagic process, has shown great potential in treating osteoarthritis and promoting diabetic foot wound healing. This review thoroughly explores the potential roles of autophagy in regulating platelet production and function, as well as in platelet-related diseases. Future research should focus on the molecular mechanisms of platelet autophagy, investigate its dynamic changes under different disease conditions, and explore how autophagy modulation can improve platelet function and treat related diseases. This will provide a theoretical foundation for developing novel therapeutic strategies and is expected to bring breakthroughs in the treatment of platelet-related diseases.

Computational analysis can accurately detect drug-gene interactions (DGIs) cost-effectively. However, transductive learning models are the hotspot to reveal the promising performance for unknown DGIs (both drugs and genes are present in the training model), without special attention to the unseen DGIs (both drugs and genes are absent in the training model). In view of this, this study, for the first time, proposed an inductive learning-based model for the precise identification of unseen DGIs. In our study, by integrating disease nodes to avoid data sparsity, a multi-relational drug-disease-gene (DDG) graph was constructed to achieve effective fusion of data on DDG intro-relationships and inter-actions. Following the extraction of graph features by utilizing graph embedding algorithms, our next step was the retrieval of the attributes of individual gene and drug nodes. In this way, a hybrid feature characterization was represented by integrating graph features and node attributes. Machine learning (ML) models were built, enabling the fulfillment of transductive predictions of unknown DGIs. To realize inductive learning, this study generated an innovative idea of transforming known node vectors derived from the DDG graph into representations of unseen nodes using node similarities as weights, enabling inductive predictions for the unseen DGIs. Consequently, the final model was superior to existing models, with significant improvement in predicting both external unknown and unseen DGIs. The practical feasibility of our model was further confirmed through case study and molecular docking. In summary, this study establishes an efficient data-driven approach through the proposed modeling, suggesting its value as a promising tool for accelerating drug discovery and repurposing.

Abstract In recent years, the prevalence of overweight and obesity among children and adolescents has risen rapidly, posing a serious threat to their physical and mental health. To provide scientific, systematic, and standardized weight management guidance for overweight and obese children and adolescents, the study focuses on the core concept of healthy lifestyle intervention, integrates multidisciplinary expert opinions and research findings,and proposes a comprehensive multidisciplinary intervention framework covering scientific exercise intervention, precise nutrition and diet, optimized sleep management, and standardized psychological support. It calls for the establishment of a multi agent collaborative management mechanism led by the government, implemented by families, fostered by schools, initiated by individuals, optimized by communities, reinforced by healthcare, and coordinated by multiple stakeholders. Emphasizing a child and adolescent centered approach, the consensus advocates for comprehensive, multi level, and personalized guidance strategies to promote the internalization and maintenance of a healthy lifestyle. It serves as a reference and provides recommendations for the effective prevention and control of overweight and obesity, and enhancing the health level of children and adolescents.

Abstract Prenatal stress is a common, systemic, nonspecific stress response that occurs during pregnancy. The gut microbiota, which is known as the “second genome” of the human body, interacts with all major systems of the body. Changes in the gut microbiota can impact the development and health of infants and young children. Advances in research technology have allowed us to uncover the relationship between prenatal stress and imbalances in offspring intestinal microbiota, as well as the development of multiple systemic diseases. However, the exact mechanisms through which prenatal stress disrupts the gut microbiota of offspring remain incompletely understood. This review summarizes the existing research on diseases caused by prenatal stress disrupting the offspring intestinal flora, and seeks future research directions to expand the understanding of the pathogenesis of infant diseases.

Abstract Asthma is a well-characterized heterogeneous disease marked by airway remodeling and chronic airway inflammation. Clinically, the treatment of asthma primarily relies on hormonal drugs. However, the long-term use of these medications can lead to significant side effects. Mitophagy is a biological process that selectively transports damaged mitochondria to lysosomes for degradation. Recent research has revealed the crosstalk between mitophagy and asthma. Accordingly, taking mitophagy as an entry point, summarizing the key molecular mechanisms and regulators of mitophagy in asthma will facilitate the development of novel intervention targets and strategies for asthmatic treatment.

Objective To analyze the effect of hand transmitted vibration on fingertip thermotactile perception threshold (TPT) among grinding workers in a sports equipment manufacturing enterprise. Methods A total of 151 male grinding workers from a sports equipment manufacturing enterprise in Guangdong Province were enrolled in the vibration exposure group, and 51 male workers without hand-transmitted vibration exposure were enrolled in the control group, using the judgment sampling method. Basic health conditions of the workers were surveyed in both groups. The TPTs of the distal phalanges of the index and little fingers on both hands were tested using an HVLab thermal perception tester. Results The detection rates of finger numbness and tingling among workers in the vibration exposure group were higher than those in the control group (92.1% vs 7.8% and 59.6% vs 0.0%, respectively, both P<0.01). The detection rates of numbness or tingling of different fingers in the vibration exposure group descended in the following order: index finger, middle finger, ring finger, thumb and little finger. The hot threshold of the index finger and little finger increased (all P<0.01), while the cold threshold decreased (all P<0.01) in the vibration exposure group, compared with the control group. The results of generalized linear regression analysis showed that with the increase of the duration of hand-transmitted vibration, the hot threshold of the index finger and the little finger of both hands increased (all P<0.01), and the cold threshold decreased (all P<0.01). The hot thresholds of workers with numbness of both the index fingers and left little finger were higher than those of workers without numbness of the same finger (all P<0.05). The hot threshold of workers with tingling of the left index finger was higher than those without tingling (P<0.05). The cold thresholds of workers with tingling of the both index fingers and left little finger were lower than those without tingling of the same finger (all P<0.05). The hot threshold of the right little finger increased with age (P<0.01), while the cold thresholds of both little fingers decreased with age (all P<0.01). Conclusion Hand-transmitted vibration exposure increases fingertip hot threshold and decreases fingertip cold threshold of workers exposed to hand-transmitted vibration. Years of service in hand-transmitted vibration work, finger numbness or tingling, and age were influencing factors of TPT. Fingertip TPT examination can be used to assist in the early detection of vibration-induced nerve injury in workers exposed to hand-transmitted vibration.

Computational analysis can accurately detect drug-gene interactions(DGIs)cost-effectively.However,transductive learning models are the hotspot to reveal the promising performance for unknown DGIs(both drugs and genes are present in the training model),without special attention to the unseen DGIs(both drugs and genes are absent in the training model).In view of this,this study,for the first time,proposed an inductive learning-based model for the precise identification of unseen DGIs.In our study,by integrating disease nodes to avoid data sparsity,a multi-relational drug-disease-gene(DDG)graph was constructed to achieve effective fusion of data on DDG intro-relationships and inter-actions.Following the extraction of graph features by utilizing graph embedding algorithms,our next step was the retrieval of the attributes of individual gene and drug nodes.In this way,a hybrid feature charac-terization was represented by integrating graph features and node attributes.Machine learning(ML)models were built,enabling the fulfillment of transductive predictions of unknown DGIs.To realize inductive learning,this study generated an innovative idea of transforming known node vectors derived from the DDG graph into representations of unseen nodes using node similarities as weights,enabling inductive predictions for the unseen DGIs.Consequently,the final model was superior to existing models,with significant improvement in predicting both external unknown and unseen DGIs.The practical feasibility of our model was further confirmed through case study and molecular docking.In summary,this study establishes an efficient data-driven approach through the proposed modeling,suggesting its value as a promising tool for accelerating drug discovery and repurposing.

Objective To investigate the role and mechanism of ginsenoside Rk3 in alleviating the senescence of retinal pigment epithelial(RPE)cells and in treating neovascular age-related macular degeneration(nAMD).Methods An ARPE-19 cell senescence model induced by hydrogen peroxide and an nAMD mouse model were subjected to validate the pharmacological activity of ginsenoside Rk3 in reducing RPE cell senescence and shrinking choroidal neovascularization(CNV)area.Transcriptome sequencing was performed to analyze the changes in differential gene expression profiles.Western blotting was used to detect the expression levels of mTOR,S6K1,p-S6K1,4EBP1,p-4EBP1,p62,and LC3A/B.Molecular docking and dynamics simulations were conducted to analyze the binding affinity of ginsenoside Rk3 with mTOR protein.Results ① Cell experiments showed that ginsenoside Rk3 significantly alleviated the senescence in ARPE-19 cells(P<0.05).② Animal experiments confirmed that ginsenoside Rk3 significantly reduced the retinal CNV area in nAMD mice(P<0.01),and its efficacy was comparable to the first-line clinical drug aflibercept(P>0.05).③ Transcriptome sequencing suggested that ginsenoside Rk3 led to enrichment of the PI3K-Akt signaling pathway.Western blotting showed that ginsenoside Rk3 inhibited the overactivation of mTORC1 signaling(P<0.05)and simultaneously enhanced cellular autophagy(P<0.05).④ Molecular docking and dynamics simulations further validated that ginsenoside Rk3 probably targets mTOR to alleviate RPE cell senescence.Conclusion Ginsenoside Rk3 alleviates RPE cell senescence and reduces retinal CNV area in nAMD mice by enhancing autophagy through inhibition of mTOR.

Objective To investigate the mechanism by which Biejiajian Pill(BJJP)regulates ferroptosis in hepatocellular carcinoma(HCC)cells through the p62/Keap1/NRF2 pathway and to provide an experimental basis for its application in the prevention and treatment of HCC.Methods Huh7 HCC cells were divided into a normal control group,a BJJP drug serum group,an erastin(a ferroptosis inducer)group,a BJJP drug serum+erastin group,and BJJP drug serum+ferrostatin-1(Fer-1)(a ferroptosis inhibitor)group.BJJP drug serum was prepared with animals treated with BJJP and CCK-8 assay was performed to determine the optimal concentration and duration of BJJP intervention.The levels of intracellular iron(Fe),reduced glutathione(GSH),lipid peroxides(MDA),and reactive oxygen species(ROS)were measured.Western blot was performed to determine the expression levels of FTH1,GPX4,xCT,SLC40A1,Keapl,p62,and NRF2.JC-1 staining was performed to measure mitochondrial membrane potential,and cell immunofluorescence was performed to determine the expression of p62 and Keap1.Results According to the CCK-8 assay results,the cell inhibition rate was highest when BJJP was administered at a high dose of 2.2 g/kg(P＜0.001).Furthermore,the inhibition rate of Huh7 cells was highest when Huh7 cells were treated with high-dose BJJP drug serum for 48 h.Therefore,the serum concentration of high-dose BJJP and 48 h were selected as the treatment dose and duration for the subsequent experiment.Compared with the control group,the BJJP drug serum group,the erastin group,and the BJJP drug serum+erastin group showed increased iron content,decreased GSH content,increased MDA levels,increased ROS aggregation,decreased FTH1,GPX4,xCT,SLC40A1,p62,and NRF2 contents,increased Keap1 content,and decreased mitochondrial membrane potential(P＜0.05).Conclusion BJJP regulates ferroptosis in Huh7 HCC cells by inhibiting the p62/Keap1/NRF2 pathway,demonstrating potentials as a therapeutic agent for HCC.

Objective To explore the application of case-based learning(CBL)approach in the basic medical stage for eight-year clinical medical program.Methods A total of 320 students from the eight-year clinical medicine pro-gram at Peking Union Medical College in the grades of 2014-2015 and 2019-2020 were selected as the study subjects.These students were divided into two groups,162 students in the classes of 2014 and 2015 as the control group,and 158 students in the classes of 2019 and 2020 as the experimental group.The students in the control group received classic teaching in the basic medicine stage characterized by traditional lectures as the main teaching method.The students in the experimental group received traditional lectures supplemented by CBL.In this study,the cardiovascular system was taken as an example,and the assessment scores and questionnaires of the two groups of students were collected in order to evaluate the teaching effectiveness and to obtain timely teaching feedback.Results Traditional lecture combined with CBL method significantly improved the theory assessment scores of students in the experimental group,stimulated learning interest and intrinsic motivation,and enhanced team learn-ing and problem-solving ability.Students believed that CBL teaching could effectively improve the ability to link theory to clinical practice.In addition,CBL teaching method encouraged the interaction between teachers and students and improved teaching efficiency.Conclusions Well-designing and well-organized CBL teaching from multiple levels,including teachers,students,and curricula,can be better accepted and acknowledged by students from eight-year clinical medical program at the stage of basic medical education.