Objective To explore the effect of SGLT2 inhibitor(SGLT2i)Dagaglipzin(Dap)on mitochondrial autophagy in cardiomyocytes in diabetic cardiomyopathy(DCM)by regulating mitochondrial membrane transporter TOM20.Methods H9C2 cardiomyocytes cultured in vitro were divided into normal control(Con)group,HG+PA group,knockout TOM20(HG+PA+siTOM20)group,knockout control(HG+PA+siNC)group,Dap intervention(HG+PA+Dap)group,and solvent control(HG+PA+DMSO)group.The expression of TOM20 was predicted by RNA-seq second-generation sequencing in HG+PA group.The expression of TOM20 and mitochondrial autophagy related proteins was detected by Western blot,the mitochondrial membrane potential was measured by immunofluorescence staining,and the mitochondrial autophagy level was evaluated by transmission electron microscopy.Results Compared with Con group,protein expressions of TOM20 and P62 were increased(P<0.05),while protein expressions of ULK1,Parkin,Beclin1 and LC3-B were decreased(P<0.05),mitochondrial membrane potential was destroyed,the number of mitochondrial autophagosomes was reduced,and autophagy activity was inhibited in HG+PA group.Compared with HG+PA+siNC group and HG+PA+DMSO group,the protein expressions of TOM20 and P62 were decreased(P<0.05),while the protein expressions of ULK1,Parkin,Beclin1 and LC3-B were increased(P<0.05),the damage of mitochondrial membrane potential decreased,the number of mitochondrial autophagosomes increased,and the inhibition of autophagy activity reversed in HG+PA+siTOM20 and HG+PA+DAPA groups.Conclusions SGLT2 inhibitors appear to partially restore mitochondrial function in diabetic cardiomyopathy by suppressing TOM20 expression,potentially through activation of mitochondrial autophagy.

There is a substantial unmet need for treatments in the field of pediatric rare diseases, and investigator initiated trial(IIT) provide a critical pathway for testing and developing new drugs or treatment strategies. However, healthcare institutions, when conducting such research, must address compliance risks related to project approval, contract management, data protection, and conflict of interest management. This study aims to analyze the particularities and challenges of IIT in pediatric rare diseases, review relevant regulations and regulatory requirements, and provide healthcare institutions with a reference framework for compliance risk management to maximize the benefits of IIT. Based on literature review, analysis of laws and regulations, practical work experience, and frameworks from other institutions, we summarize the unique aspects of pediatric rare disease IIT in terms of participant characteristics, innovative technologies, and organizational structures.On this basis, targeted compliance management recommendations are proposed, which include establishing a risk rating and full-cycle risk monitoring mechanism, a consent and ethical review mechanism tailored to pediatric participants, a robust contract management mechanism, a comprehensive data security management mechanism, and a multidisciplinary team and multi-channel compensation mechanism. The study concludes that healthcare institutions, funders, and other collaborating entities should implement compliance management in line with the characteristics of IIT to ensure the safety and effectiveness of research and facilitate innovation and development in the treatment of pediatric rare diseases.

Objective To explore the effect of SGLT2 inhibitor(SGLT2i)Dagaglipzin(Dap)on mitochondrial autophagy in cardiomyocytes in diabetic cardiomyopathy(DCM)by regulating mitochondrial membrane transporter TOM20.Methods H9C2 cardiomyocytes cultured in vitro were divided into normal control(Con)group,HG+PA group,knockout TOM20(HG+PA+siTOM20)group,knockout control(HG+PA+siNC)group,Dap intervention(HG+PA+Dap)group,and solvent control(HG+PA+DMSO)group.The expression of TOM20 was predicted by RNA-seq second-generation sequencing in HG+PA group.The expression of TOM20 and mitochondrial autophagy related proteins was detected by Western blot,the mitochondrial membrane potential was measured by immunofluorescence staining,and the mitochondrial autophagy level was evaluated by transmission electron microscopy.Results Compared with Con group,protein expressions of TOM20 and P62 were increased(P<0.05),while protein expressions of ULK1,Parkin,Beclin1 and LC3-B were decreased(P<0.05),mitochondrial membrane potential was destroyed,the number of mitochondrial autophagosomes was reduced,and autophagy activity was inhibited in HG+PA group.Compared with HG+PA+siNC group and HG+PA+DMSO group,the protein expressions of TOM20 and P62 were decreased(P<0.05),while the protein expressions of ULK1,Parkin,Beclin1 and LC3-B were increased(P<0.05),the damage of mitochondrial membrane potential decreased,the number of mitochondrial autophagosomes increased,and the inhibition of autophagy activity reversed in HG+PA+siTOM20 and HG+PA+DAPA groups.Conclusions SGLT2 inhibitors appear to partially restore mitochondrial function in diabetic cardiomyopathy by suppressing TOM20 expression,potentially through activation of mitochondrial autophagy.

Objective To explore the diagnosis and treatment experience of malignant peritoneal mesothelioma by analyzing the clinical characteristics of patients with single center peritoneal mesothelioma.Methods Retrospec-tively analyze the clinical data,including age and treatment regimens,of 99 patients with malignant peritoneal mes-othelioma admitted to Peking Union Medical College Hospital from June 2012 to July 2023.Kaplan-Meier for surviv-al analysis and Logistic and Cox regression were applied to assess the impact of factors like age and treatment regi-mens on survival time.Results The median age of diagnosis for 99 patients with peritoneal mesothelioma was 56 years,of which 82 were pathologically diagnosed.Among them,38 cases(51.4%)underwent tumor cell reduction surgery,and 57 cases(77.0%)underwent systemic or local treatment.The median survival time for all patients was 43 years.The age of diagnosis may affect the prognosis of patients with malignant mesothelioma,and those aged≥65 at the time of diagnosis have a worse prognosis.Conclusions Malignant peritoneal mesothelioma is a rare but invasive malignant tumor with a poor prognosis.There is still a need to develop novo drugs and comprehensive treat-ment strategies.

OBJECTIVE: To propose a machine learning-based method for predicting the trajectories during manual acupuncture manipulation (MAM), aiming to improve the precision and consistency of acupuncture practitioner' operation and provide the real-time suggestions on MAM error correction. METHODS: Computer vision technology was used to analyze the hand micromotion when holding needle during acupuncture, and provide a three-dimensional coordinate description method of the index finger joints of the holding hand. Focusing on the 4 typical motions of MAM, a machine learning-based MAM trajectory predictive model was designed. By integrating the changes of phalangeal joint angle and hand skeletal information of acupuncture practitioner, the motion trajectory of the index finger joint was predicted accurately. Besides, the roles of machine learning-based MAM trajectory predictive model in the skill transmission of acupuncture manipulation were verified by stratified randomized controlled trial. RESULTS: The performance of MAM trajectory predictive model, based on the long short-term memory network (LSTM), obtained the highest stability and precision, up to 98%. The learning effect was improved when the model applied to the skill transmission of acupuncture manipulation. CONCLUSION The machine learning-based MAM predictive model provides acupuncture practitioner with precise action prediction and feedback. It is valuable and significant for the inheritance and error correction of manual operation of acupuncture.
Humans ; Acupuncture Therapy/instrumentation* ; Machine Learning ; Adult ; Male ; Female

OBJECTIVE: To investigate the effect of manual acupuncture manipulations (MAMs) on subcutaneous muscle tissue, by developing quantitative models of "lifting and thrusting" and "twisting and rotating", based on machine learning techniques. METHODS: A depth camera was used to capture the acupuncture operator's hand movements during "lifting and thrusting" and "twisting and rotating" of needle. Simultaneously, the ultrasound imaging was employed to record the muscle tissue responses of the participants. Amplitude and angular features were extracted from the movement data of operators, and muscle fascicle slope features were derived from the data of ultrasound images. The dynamic time warping barycenter averaging algorithm was adopted to align the dual-source data. Various machine learning techniques were applied to build quantitative models, and the performance of each model was compared. The most optimal model was further analyzed for its interpretability. RESULTS: Among the quantitative models built for the two types of MAMs, the random forest model demonstrated the best performance. For the quantitative model of the "lifting and thrusting" technique, the coefficient of determination (R²) was 0.825. For the "twisting and rotating" technique, R² reached 0.872. CONCLUSION Machine learning can be used to effectively develop the models and quantify the effects of MAMs on subcutaneous muscle tissue. It provides a new perspective to understand the mechanism of acupuncture therapy and lays a foundation for optimizing acupuncture technology and designing personalized treatment regimen in the future.
Humans ; Acupuncture Therapy/methods* ; Machine Learning ; Male ; Adult ; Female ; Subcutaneous Tissue/diagnostic imaging* ; Young Adult

Objective To develop a postoperative precision nursing program for children with obstructive sleep apnea-hypopnea syndrome(OSAHS),so as to provide references for the improvement of nursing quality for children with OSAHS.Methods Literature in precision nursing for children with OSAHS was systematically reviewed and summarised based on precision nursing theory and a postoperative precision nursing program was drafted.Using the Delphi's Method,two rounds of expert consultation were conducted and the postoperative precision nursing program for children with OSAHS was revised and finalised.Results The response rates of the two rounds of expert consultation were 100.00%with the expert authority coefficient of 0.875.The Kendall coefficient of concordance(W)of levels 1,2 and 3 indices in the second round of expert consultation were 0.289,0.203,0.187,respectively(all P<0.01).The importance score of each inclicator ranged from 4.50～4.94.The coefficient of variations for the three-level indices ranged from 0.05 to 0.21.The finalised program composed 8 level-1 indices(postoperative position assessment,intervention,prevention and care of bleeding,maintaining postoperative airway patency,postoperative nausea and vomiting care,postoperative pain assessment and care,dietary care,complication prevention and care,discharge guidance),16 level-2 indices,and 22 level-3 indices.Conclusion The postoperative precision nursing program for the children with OSAHS is scientific,innovative and applicable.It provides clinical references for nursing of the children with OSAHS.

Objective To develop a postoperative precision nursing program for children with obstructive sleep apnea-hypopnea syndrome(OSAHS),so as to provide references for the improvement of nursing quality for children with OSAHS.Methods Literature in precision nursing for children with OSAHS was systematically reviewed and summarised based on precision nursing theory and a postoperative precision nursing program was drafted.Using the Delphi's Method,two rounds of expert consultation were conducted and the postoperative precision nursing program for children with OSAHS was revised and finalised.Results The response rates of the two rounds of expert consultation were 100.00%with the expert authority coefficient of 0.875.The Kendall coefficient of concordance(W)of levels 1,2 and 3 indices in the second round of expert consultation were 0.289,0.203,0.187,respectively(all P<0.01).The importance score of each inclicator ranged from 4.50～4.94.The coefficient of variations for the three-level indices ranged from 0.05 to 0.21.The finalised program composed 8 level-1 indices(postoperative position assessment,intervention,prevention and care of bleeding,maintaining postoperative airway patency,postoperative nausea and vomiting care,postoperative pain assessment and care,dietary care,complication prevention and care,discharge guidance),16 level-2 indices,and 22 level-3 indices.Conclusion The postoperative precision nursing program for the children with OSAHS is scientific,innovative and applicable.It provides clinical references for nursing of the children with OSAHS.

Objective This article systematically reviews the interaction between autophagy and herb-induced liver injury,and it elucidates the mechanism of liver injury.Also,it summarizes the control strategies of herb-induced liver injury.Methods Based on the retrieval of CNKI,Wanfang,PubMed and Web-of-Science databases,the literature on autophagy and herb-induced liver injury in the past decade was reviewed to clarify the relationship between autophagy and disease occurrence.Then we summarize common drugs and the mechanism of herb-induced liver injury caused by autophagy.The control strategies of herb-induced liver injury were summarized,too.Results Autophagy plays a dual role in the herb-induced liver injury.Autophagy pathway and autophagy-related molecules can be changed in the case of excessive activation or excessive inhibition to cause herb-induced liver injury.Conclusion The regulation of autophagy pathway is expected to be a new method for the prevention and treatment of herb-induced liver injury.Targeted control strategies are important measures to realize the safety risk monitoring of Chinese herbal medicine.

ObjectiveTo decipher the mechanism of Danshenyin in regulating platelet activation in the rat model of hyperlipidemia by means of proteomics and molecular biology. MethodWistar rats were randomized into blank， model， and Danshenyin groups （n=10） according to the blood lipid level. The rats in the blank group were fed with a basic diet， and those in the model and Danshenyin groups with a high-fat diet. All the rats had free access to water and food. The treatment began at the 9th week. The rats in the Danshenyin group were administrated with Danshenyin by gavage at a crude drug dose of 3.6 g·kg^-1. The rats in the model and blank groups were administrated with an equal volume of normal saline according to body weight. At the 12th week， the tissue samples were collected for the measurement of related indicators， and the blood lipid level was measured by an automatic biochemical analyzer. The whole blood viscosity and plasma viscosity were measured by an automatic hemorheometer. The platelet proteome was determined by liquid chromatography-mass spectrometry. Western blotting was employed to determine the protein levels of platelet membrane glycoprotein 4 （CD36）， focal adhesion kinase （FAK）， phosphatidylinositol 4-phosphate 5-kinase （PIP5K）， phosphorylated phosphatidylinositol 3-kinase （p-PI3K）， protein kinase B （Akt）， and phosphorylated protein kinase B （p-Akt）. ResultCompared with the model group， Danshenyin lowered the levels of total cholesterol （TC）， triglyceride （TG）， and low-density lipoprotein cholesterol （LDL-C） in the plasma （P<0.05）， elevated the level of high-density lipoprotein cholesterol （HDL-C） （P<0.05）， and reduced the platelet aggregation rate （P<0.05）. Compared with the blank group， the modeling up-regulated the expression of 44 proteins and down-regulated the expression of 12 proteins. Compared with the model group， Danshenyin up-regulated the expression of 21 proteins and down-regulated the expression of 22 proteins. Compared with the blank group， Danshenyin up-regulated the expression of 31 proteins and down-regulated the expression of 49 proteins. The gene ontology （GO） functional enrichment showed that the differentially expressed proteins were mainly involved in cholesterol transport and efflux， production of cytokines， dyslipidemia， and platelet activation. The Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment showed that the differentially expressed proteins were mainly involved in ECM-receptor interaction， peroxisome proliferators-activated receptors （PPAR）， focal adhesion， and PI3K/Akt signaling pathways. Danshenyin can significantly down-regulate the expression of CD36， FAK， PIP5K， PI3K， p-Akt （Ser473）， and p-Akt1/2/3 （Thr308）. ConclusionDanshenyin can restore the blood lipid level of hyperlipidemia rats and inhibit the platelet activation caused by abnormal lipid levels by down-regulating the CD36/PI3K/Akt signal cascade.