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 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 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 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 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.

Lung cancer is the most common malignant tumor of the respiratory system， and its pathogenesis is still not fully understood. Despite the significant clinical efficacy achieved through treatments such as surgery， radiotherapy， chemotherapy， targeted therapy， and immunotherapy， they still come with many complications and significant adverse reactions. In recent years， numerous basic and clinical studies have confirmed the effectiveness of Chinese medicine in treating lung cancer. Chinese medicine features synergistic regulation through its multiple components， targets， pathways， and approaches. Active monomeric constituents in Chinese medicine are diverse， and their mechanisms of action are intricate， making it challenging to fully understand the mechanisms by which Chinese medicine prevents and treats lung cancer. Therefore， there is an urgent need to approach Chinese medicine intervention in lung cancer from a modern medical perspective， exploring the mechanisms of Chinese medicine intervention in lung cancer at the molecular biology and network pharmacology levels. According to traditional Chinese medicine （TCM）， the occurrence of lung cancer is predominantly attributed to factors such as deficiency of healthy Qi， presence of pathogenic factors， internal accumulation of heat-toxins， internal accumulation of phlegm-dampness， and Qi stagnation and blood stasis. Literature analysis reveals that Chinese medicine compound formulas for lung cancer predominantly include tonifying agents and heat-clearing and toxin-removing agents， such as Shashen Maidongtang， Xiaoyan prescription， and Feijinsheng prescription. The single herbs used mainly include heat-clearing， deficiency-tonifying， blood-activating， stasis-resolving， phlegm-resolving， cough-relieving， and asthma-calming categories. The use of Chinese medicine aligns with the TCM understanding of the etiology and pathogenesis of lung cancer. Studies have shown that TCM can regulate the expression of key molecules in lung cancer-related signaling pathways， such as the phosphatidylinositol 3-kinase/protein kinase B （PI3K/Akt）， nuclear factor-kappa B （NF-κB）， Wnt/β-catenin， mitogen-activated protein kinase （MAPK）， and Janus kinase/signal transducer and activator of transcription （JAK/STAT）， thereby exerting effects such as reducing lung cancer cell activity， blocking the cell cycle， inhibiting proliferation and invasion of lung cancer cells， inducing apoptosis in lung cancer cells， promoting cell autophagy， and reversing drug resistance， and intervening in the progression of lung cancer. This study systematically summarized recent research progress on how Chinese medicine monomers or formulas regulated the aforementioned signaling pathways and key protein expression to exert anti-lung cancer effects， aiming to elucidate the mechanisms by which Chinese medicine intervenes in the progression of lung cancer and provide insights and theoretical basis for further research and clinical application of Chinese medicine in lung cancer intervention.

Circular RNA(circRNA)is an emerging class of endogenous non-coding RNA,which is widely expressed in the brain and plays an important role in a variety of biological processes.Research has shown that circRNA plays a key role in physiological and pathological processes of the brain,such as neurodevelopment,synaptic plasticity and neurodegenerative diseases through a variety of mecha-nisms such as adsorption of microRNA,binding to proteins and translation of peptides.In the field of drug addiction,the expression of circRNA is significantly changed in animal models and brains of addicts,and the regulation involves neural adaptation in brain regions that form the reward circuit such as the nucleus accumbens and prefrontal cortex.Additionally,addiction-related circRNAs are closely associated with neurotransmitter systems,signaling pathways,and neuroinflammatory responses,and they influ-ence the formation and maintenance of drug addiction by modulating gene expression networks related to drug addiction.Here,the biogenesis and regulatory mechanism of circRNA as well as its important role in brain function and drug addiction are reviewed in order to provide a new perspective for explora-tions of the pathological mechanism of drug addiction.