ObjectiveCleft palate (CP) is a common congenital deformity often associated with velopharyngeal insufficiency (VPI), which disrupts the physiological coupling between respiration and speech. Conventional clinical assessments, such as nasometry and spirometry, provide limited static data and fail to visualize the dynamic spatiotemporal distribution of lung ventilation during phonation. This study introduces spatiotemporal electrical impedance tomography (ST-EIT) to evaluate speech-respiratory functional features in CP patients compared to normal controls (NC). The aim is to characterize multi-domain respiratory patterns and to validate an interpretable machine learning framework for providing objective, quantitative evidence for clinical assessment. MethodsSeventy-five participants were enrolled in this study, comprising 37 patients with surgically repaired CP and 38 healthy volunteers matched for age, gender, and body mass index (BMI). All subjects performed standardized sustained phonation tasks while undergoing synchronous monitoring with a 16-electrode EIT system and a pneumotachograph. A comprehensive feature engineering pipeline was developed to extract physiological parameters across 3 complementary domains. (1) Temporal domain: including inspiratory/expiratory phase duration (tPhase), time constants (Tau), and inspiratory-to-expiratory time ratios (TI/TE); (2) airflow domain: comprising mean flow, peak flow, and instantaneous flow at 25%, 50%, and 75% of tidal volume; and (3) spatial domain: quantifying global and regional tidal impedance variation (TIV), global inhomogeneity (GI), and center of ventilation (CoV). Extreme Gradient Boosting (XGBoost) classifiers were trained using 5 distinct data sources (Spirometry, Nasometry, Inspiratory-EIT, Expiratory-EIT, and fused ST-EIT). Model performance was rigorously evaluated via stratified 5-fold cross-validation, and Shapley additive explanations (SHAP) were employed to quantify global and local feature contributions. ResultsThe CP group exhibited a distinct respiratory phenotype compared to controls. In the temporal domain, CP patients showed significantly shorter inspiratory (1.60 s vs.1.85 s, P<0.001) and expiratory phase durations (2.45 s vs. 3.95 s, P<0.001), indicating a rapid, shallow breathing rhythm. In the airflow domain, while inspiratory flows were comparable, the CP group demonstrated significantly elevated mean and peak flows during the expiratory phase (P<0.001), reflecting compensatory respiratory effort. Spatially, CP patients presented significant ventilation redistribution, characterized by higher regional TIV in the right-anterior (ROI1) and left-posterior (ROI4) quadrants, but lower TIV in the left-anterior (ROI2) quadrant. In terms of diagnostic accuracy, the multi-modal ST-EIT model achieved the highest performance (AUC: 0.915±0.012, Accuracy: 0.843±0.019, F1-score: 0.872±0.017), substantially outperforming models based on spirometry (AUC: 0.721) or nasometry (AUC: 0.625) alone. Interpretability analysis revealed that spatial domain features were the most critical, contributing 53.4% to the model’s decision-making, followed by temporal (25.0%) and airflow (21.6%) features. ConclusionST-EIT successfully captures the temporal, airflow, and spatial deviations in CP speech respiration that are undetectable by conventional methods—specifically, rapid phase transitions, hyperdynamic expiratory airflow, and regional ventilation heterogeneity. This study validates ST-EIT as a robust, non-invasive, and radiation-free tool for characterizing speech-respiratory dysfunction, offering high clinical value for bedside screening, rehabilitation planning, and longitudinal monitoring of patients with cleft palate.

ObjectiveCleft palate (CP) is a common congenital deformity often associated with velopharyngeal insufficiency (VPI), which disrupts the physiological coupling between respiration and speech. Conventional clinical assessments, such as nasometry and spirometry, provide limited static data and fail to visualize the dynamic spatiotemporal distribution of lung ventilation during phonation. This study introduces spatiotemporal electrical impedance tomography (ST-EIT) to evaluate speech-respiratory functional features in CP patients compared to normal controls (NC). The aim is to characterize multi-domain respiratory patterns and to validate an interpretable machine learning framework for providing objective, quantitative evidence for clinical assessment. MethodsSeventy-five participants were enrolled in this study, comprising 37 patients with surgically repaired CP and 38 healthy volunteers matched for age, gender, and body mass index (BMI). All subjects performed standardized sustained phonation tasks while undergoing synchronous monitoring with a 16-electrode EIT system and a pneumotachograph. A comprehensive feature engineering pipeline was developed to extract physiological parameters across 3 complementary domains. (1) Temporal domain: including inspiratory/expiratory phase duration (tPhase), time constants (Tau), and inspiratory-to-expiratory time ratios (TI/TE); (2) airflow domain: comprising mean flow, peak flow, and instantaneous flow at 25%, 50%, and 75% of tidal volume; and (3) spatial domain: quantifying global and regional tidal impedance variation (TIV), global inhomogeneity (GI), and center of ventilation (CoV). Extreme Gradient Boosting (XGBoost) classifiers were trained using 5 distinct data sources (Spirometry, Nasometry, Inspiratory-EIT, Expiratory-EIT, and fused ST-EIT). Model performance was rigorously evaluated via stratified 5-fold cross-validation, and Shapley additive explanations (SHAP) were employed to quantify global and local feature contributions. ResultsThe CP group exhibited a distinct respiratory phenotype compared to controls. In the temporal domain, CP patients showed significantly shorter inspiratory (1.60 s vs.1.85 s, P<0.001) and expiratory phase durations (2.45 s vs. 3.95 s, P<0.001), indicating a rapid, shallow breathing rhythm. In the airflow domain, while inspiratory flows were comparable, the CP group demonstrated significantly elevated mean and peak flows during the expiratory phase (P<0.001), reflecting compensatory respiratory effort. Spatially, CP patients presented significant ventilation redistribution, characterized by higher regional TIV in the right-anterior (ROI1) and left-posterior (ROI4) quadrants, but lower TIV in the left-anterior (ROI2) quadrant. In terms of diagnostic accuracy, the multi-modal ST-EIT model achieved the highest performance (AUC: 0.915±0.012, Accuracy: 0.843±0.019, F1-score: 0.872±0.017), substantially outperforming models based on spirometry (AUC: 0.721) or nasometry (AUC: 0.625) alone. Interpretability analysis revealed that spatial domain features were the most critical, contributing 53.4% to the model’s decision-making, followed by temporal (25.0%) and airflow (21.6%) features. ConclusionST-EIT successfully captures the temporal, airflow, and spatial deviations in CP speech respiration that are undetectable by conventional methods—specifically, rapid phase transitions, hyperdynamic expiratory airflow, and regional ventilation heterogeneity. This study validates ST-EIT as a robust, non-invasive, and radiation-free tool for characterizing speech-respiratory dysfunction, offering high clinical value for bedside screening, rehabilitation planning, and longitudinal monitoring of patients with cleft palate.

ObjectiveBiochemistry and Molecular Biology, a discipline that elucidates life phenomena at the molecular level, serves as a core foundational course in medical education. It provides the theoretical basis for studying other basic and clinical medical subjects, as well as for understanding pathogenesis, disease diagnosis, and treatment. However, its complex content and highly abstract concepts have posed a dual challenge to traditional teaching models: “inefficient instruction” and “inadequate learning outcomes”. Within limited classroom hours, how to engage students and stimulate their intrinsic motivation, and how to help them recognize, understand, and develop a passion for biochemistry from the perspective of the discipline’s essence, have long been key focuses of curriculum research. MethodsUsing the lipid metabolism chapter as an example, this study employs “Rain Classroom”, a generative artificial intelligence (AI)-assisted platform, to support education in four dimensions: teaching, learning, evaluation, and research. In teaching, it assists instructors through virtual experiments, lesson preparation support, knowledge mapping, and assignment design. For learning, it serves as an intelligent study assistant for students, providing automated assignment review, enabling educational resource sharing, and facilitating personalized learning pathways. In evaluation, the platform automates assignment grading, analyzes student performance data, and offers diagnostic feedback and teaching recommendations. In research, it aids educators in collecting and analyzing teaching data, as well as searching for and summarizing relevant literature. ResultsThe results indicate that an educational model integrating teacher-led instruction, student-centered learning, and generative AI assistance significantly enhances teaching quality, students’ self-directed learning abilities, and knowledge mastery. Furthermore, with the support of generative AI, curriculum-based ideological education—focusing on cutting-edge disciplinary advances and topical medical issues—helps cultivate students’ medical spirit of “honoring life and healing the wounded”, thereby fostering the establishment of appropriate professional values. Finally, while generative AI presents both opportunities and challenges for higher education, this study also analyzes potential risks in its teaching applications, emphasizing the need for both instructors and students to avoid over-reliance and to ensure that technological tools consistently serve the fundamental goals of education. ConclusionThis study demonstrates that integrating generative AI, specifically via the “Rain Classroom” platform, can effectively enhance biochemistry education. By supporting teaching, learning, evaluation, and research, this approach improves both educational effectiveness and student outcomes. It also facilitates the incorporation of cutting-edge knowledge and professional ethics, nurturing a patient-centered mindset. Additionally, the study addresses potential implementation risks to ensure that such technological tools remain aligned with the core purpose of education.

Background: and Purpose Vertebrobasilar fusiform aneurysms (VBFAs) carry substantial morbidity and mortality, but optimal management for unruptured VBFAs remains unclear. We compared the safety and efficacy of conservative management (CM), stent-assisted coiling (SAC), and flow diverters (FDs) in patients with unruptured VBFAs, focusing on long-term prognosis. Methods: This study included data from a nationwide Chinese cohort of patients with vertebrobasilar dissecting aneurysms. Inverse probability of treatment weighting (IPTW) balanced confounders across groups. The primary outcome was poor prognosis (modified Rankin Scale score >2). Secondary outcomes included aneurysm rupture, ischemic stroke, compression symptoms, and VBFA-related deaths. Logistic regression estimated odds ratios (ORs) and 95% confidence intervals (CIs). Subgroup and sensitivity analyses were performed. Results: Among 1,115 patients with unruptured VBFAs, 838 (median age, 54 years; 655 men) were included. After IPTW, baseline characteristics were balanced. Median follow-up was 54 months. FD was associated with a lower risk of poor prognosis than CM (OR, 0.48 [95% CI, 0.30 to 0.77]; p=0.002), with no difference between CM and SAC. FD also reduced aneurysm rupture (OR, 0.20 [95% CI, 0.07 to 0.60]; p=0.004) and compression symptoms (OR, 0.30 [95% CI, 0.13 to 0.68]; p=0.004) versus CM. Time-to-event analyses further revealed significant differences in vertebral artery lesions and Type I–II VBFAs, whereas no significant differences were observed in basilar or vertebrobasilar junction lesions or in Type III–IV VBFAs. Conclusions Compared with CM, FD was associated with improved long-term outcomes in unruptured VBFAs, particularly in vertebral artery lesions and Type I–II VBFAs, although residual confounding cannot be excluded.

ObjectiveHepatocellular carcinoma (HCC) represents 90% of all primary liver cancers. The main risk factors associated with HCC include viral hepatitis (B and/or C), alcohol abuse, and metabolic dysfunction-associated steatotic liver disease (MASLD), which progressively advance to liver fibrosis, cirrhosis, and ultimately evolve into HCC. Surgical resection represents the most effective treatment for HCC, while recent advances in immunotherapy, including immune checkpoint inhibitors and adoptive cell therapies, have provided improved treatment prospects for patients with unresectable HCC. However, the complex metabolic heterogeneity of HCC limits the therapeutic efficacy. Metabolic intermediates acyl-CoA not only provide energy and substrates for numerous biochemical reactions but also serve as donors for protein lysine acylation, a major class of post-translational modification (PTM). Therefore, a deeper understanding of the molecular mechanisms underlying protein lysine acylation and hepatocarcinogenesis is urgently needed. MethodsThe levels of protein lysine acylation and silence information regulator 5 (SIRT5) expression levels in clinical HCC samples were analyzed by Western blot. Quantitative malonylome and succinylome of HCC samples were analyzed by antibody-based affinity enrichment coupled with tandem mass spectrometry. The proliferation of HCC cells was analyzed with Cell Counting Kit-8 (CCK-8) assays, the apoptosis was quantified by Annexin V-FITC/propidium iodide (PI) staining coupled with flow cytometry, and the ability of cells to migrate was assayed by Transwell assays. The enzymatic activity of glutathione S-transferase Mu 1 (GSTM1) was quantified. Transgenic mice with hepatic overexpression of SIRT5 were constructed using CRISPR-Cas9, and primary hepatocarcinogenesis was induced by administration of diethylnitrosamine. ResultsWestern blot analysis indicated that the expression level of SIRT5 was elevated in clinical samples from HCC patients, and the levels of lysine malonylation, glutarylation, and succinylation were significantly reduced in HCC tissues. Knockout of SIRT5 in MHCC-97H and MHCC-97L hepatoma cells suppressed cell proliferation, and increased the percentage of apoptotic cells significantly. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses of the differentially malonylome and succinylome of HCC samples revealed significant enrichment in two major classes of biological processes: core energy metabolism (e.g., glycolysis/gluconeogenesis, tricarboxylic acid metabolic process, fatty acid beta oxidation) and detoxification and oxidative stress response (e.g., response to toxic substance, chemical carcinogenesis, reactive oxygen species (ROS)). SIRT5 removes malonylation from lysine residues in GSTM1 and restores its detoxification activity, which is crucial for the survival of hepatocytes under stressed conditions. More importantly, in vivo experiment indicated that hepatic-specific overexpression of SIRT5 in mice accelerated diethylnitrosamine-induced liver fibrosis and hepatocarcinogenesis, indicating the critical role of SIRT5 in HCC progression. ConclusionThis study highlights the previously unrecognized SIRT5-GSTM1 axis as a key regulator in hepatocarcinogenesis, and suggests a potential target for the treatment of patients with HCC.

AIM:To investigate the current status of astigmatism and its associated factors among children and adolescents from kindergarten through senior high school in Yangpu District, Shanghai, and to provide scientific evidence for the prevention and control of refractive errors.METHODS:A cluster sampling method was employed. From September to November 2024, students from 14 randomly selected schools in Yangpu District, Shanghai, were enrolled as study subjects. Autorefraction and ocular biometry were performed under non-cycloplegic conditions, and questionnaire surveys were administered. Comparisons of astigmatism degree, detection rate, and axis were made across age groups, educational stages, and sexes. Multiple linear and logistic regression analyses were conducted to identify factors associated with astigmatism.RESULTS:A total of 7 233 students aged 4-18 y were enrolled including 3 731 males, 3 502 females, with the mean age 10.13±4.18 y, astigmatism -0.76±0.82 D, and the detection rate(≤-1.00 D)was 29.23%. Both the degree and detection rate of astigmatism were correlated with age and educational stage, peaking in senior high school, with the most pronounced changes observed during primary school. Besides age, astigmatic refractive power was influenced by spherical equivalent(β=0.105, P<0.001), mean keratometry(β=-0.118, P<0.001), sex(with boys as the reference, girls: β=0.054, P<0.001), frequent sustained near work for 30-40 min(with “almost never” as the reference, β=-0.030, P=0.038), preterm birth(β=-0.023, P=0.044), maternal myopia(β=-0.028, P=0.020), and homework completion time on rest days(β=-0.035, P=0.041). The detection rate of astigmatism was associated with maternal myopia(OR=1.130, P=0.039), male sex(OR=0.773, P<0.001), shorter sleep duration on school days(OR=0.909, P=0.028), shorter sleep duration on rest days(OR=0.937, P=0.046), preterm birth(OR=1.382, P=0.012), frequent excessive head lowering(OR=1.216, P=0.045), homework completion time on rest days(OR=1.043, P=0.046), higher spherical equivalent(OR=0.891, P<0.001), and higher mean keratometry(OR=1.188, P<0.001).CONCLUSION:The degree and detection rate of astigmatism among children and adolescents from kindergarten to senior high school in Yangpu District, Shanghai are correlated with educational stage, and primary school may represent a critical period for astigmatism prevention and control. Male sex, maternal myopia, preterm birth, high-intensity near work, and insufficient sleep and other factors may be associated with the onset and progression of astigmatism. It is recommended that education and health departments strengthen visual health screening during primary school, while promoting behavioral interventions such as scientific eye-use habits and adequate sleep across different educational stages to delay the onset and progression of astigmatism.

In recent years, significant progress has been made in the field of liver transplantation in terms of donor expansion, technological innovation and perioperative management. Machine perfusion technology, through dynamic repair and assessment of donor liver quality, can effectively reduce postoperative complications and increase the utilization rate of marginal donor livers. The optimization of split liver transplantation technology combined with normothermic perfusion further alleviates the shortage of donors, but its promotion is still limited by technical barriers. Xenotransplantation has achieved preclinical breakthroughs in the field of genetically modified pig livers, but ethical and immune barrier issues need to be urgently resolved. In the field of liver cancer liver transplantation, the focus is on neoadjuvant treatment with immune checkpoint inhibitors and the development of recurrence prediction models, which promotes precise treatment. For perioperative management, the optimization of individualized immunosuppressive regimens, artificial liver support, and strategies for the prevention and control of vascular complications has significantly improved patients’ survival rates. Personalized treatment for children, elderly recipients, and recipients with multiple comorbidities provides new ideas for liver transplantation in special populations. In the future, liver transplantation research may focus on the integration of multidisciplinary approaches, individualized treatment and emerging technologies to advance the global liver transplantation cause to new heights.

Objective To explore the feasibility and clinical experience of the middle hepatic vein splitting-reconstruction technique in split liver transplantation from low-age donor livers. Methods A retrospective analysis was conducted on the cases of two low-age donor livers that underwent middle hepatic vein splitting-reconstruction, which were transplanted into four child recipients at the Liver Transplantation Center of the Third Affiliated Hospital of Sun Yat-sen University from January 2017 to July 2023. The surgical and postoperative conditions were summarized and analyzed. Results Donor 1 was a 6-year-old and 4-month-old girl with a body weight of 21 kg, and the obtained donor liver weighed 496 g. After splitting, the left and right liver weights were 201 g and 280 g, and transplanted into a 9-month-old boy weighing 6.5 kg and a 9-month-old boy weighing 7.5 kg, respectively. The graft to recipient weight ratio (GRWR) was 3.09% and 3.73%, respectively. Donor 2 was a 5-year-old and 8-month-old boy with a body weight of 19 kg, and the donor liver weighed 673 g. After splitting, the left and right liver weights were 230 g and 400 g, and transplanted into a 13-month-old girl weighing 9.5 kg and a 15-month-old boy weighing 12 kg. The GRWR was 2.42% and 3.33%, respectively. Both donor livers were split ex vivo, with the middle hepatic vein being completely split in the middle and reconstructed using allogeneic iliac vein and iliac artery vascular patches. According to GRWR, none of the 4 transplant livers were reduced in volume. Among the 4 recipients, one died due to postoperative portal vein thrombosis and non-function of the transplant liver, while the other three cases recovered smoothly without early or late complications. Regular follow-up was conducted until July 31, 2023, and liver function recovered well. Conclusions Under the premise of detailed assessment of the donor liver and meticulous intraoperative operation, as well as matching with suitable child recipients, low-age donor livers may be selected for splitting. The complete splitting and reconstruction of the middle hepatic vein in the middle may effectively ensure the adequate venous return of the left and right liver and provide sufficient functional liver volume.

Traditional Chinese Medicine (TCM), as a treasure of the Chinese nation, plays a significant role in maintaining public health. In 2019, the Central Committee of the Communist Party of China and the State Council proposed for the first time the establishment of a TCM registration and evaluation evidence system that integrates TCM theory, "personal experience" and clinical trials (referred to as the "Three-in-One" System) to promote the inheritance and innovation of TCM. Subsequently, the National Medical Products Administration issued several guiding principles to advance the improvement and implementation of this system. Owing to the complexity of its implementation, there are still differing understandings within the TCM industry regarding the positioning of the "Three-in-One" Registration and Evaluation Evidence System, as well as the connotation and value orientation of the "personal experience." To address this, Academician WANG Qi, President of the TCM Association, China International Exchange and Promotion Association for Medical and Healthcare and TCM master, led a group of academicians, TCM masters, TCM pharmacology experts and clinical TCM experts to convene a "Seminar on Promoting the Implementation of the ′Three-in-One′ Registration and Evaluation Evidence System for Chinese Medicinals." Through extensive discussions, an expert consensus was formed, clarifying the different roles of the TCM theory, "personal experience" and clinical trials within the system. It was further emphasized that the "personal experience" is the core of this system, and its data should be derived from clinical practice scenarios. In the future, the improvement of this system will require collaborative efforts across multiple fields to promote the high-quality development of the Chinese medicinal industry.

ObjectiveFat infiltration has been shown to be closely related to muscle mass loss and a variety of muscle diseases. This study proposes a method based on phase-angle electrical impedance tomography (ΦEIT) to visualize the electrical characteristic response caused by muscle fat infiltration, aiming to provide a new technical means for early non-invasive detection of muscle mass deterioration. MethodsThis study was divided into two parts. First, a laboratory pork model was constructed to simulate different degrees of fat infiltration by injecting1 ml or 2 ml of emulsified fat solution into different muscle compartments, and the phase angle images were reconstructed using ΦEIT. Second, a human experiment was conducted to recruit healthy subjects (n=8) from two age groups (20-25 years old and 26-30 years old). The fat content percentage η_fat of the left and right legs was measured by bioelectrical impedance analysis (BIA), and the phase angle images of the left and right calves were reconstructed using ΦEIT. The relationship between the global average phase angle Φ_M and the spatial average phase angle Φ_Mi of each muscle compartment and fat infiltration was further analyzed. ResultsIn the laboratory pork model, the grayscale value of the image increased with the increase of η_fat and Φ_M showed a downward trend. The results of human experiments showed that at the same fat content percentage, the Φ_M of the 26-30-year-old group was about 20%-35% lower than that of the 20-25-year-old group. The fat content percentage was significantly negatively correlated with Φ_M. In addition, the M₂ (soleus) compartment was most sensitive to fat infiltration, and the spatial average phase angles of the M₂ (soleus), M₃ (tibialis posterior and flexor digitorum longus), and M₄ (tibialis anterior, extensor digitorum longus, and peroneus longus) compartments all showed significant inter-group differences. ConclusionΦEIT imaging can effectively distinguish different degrees of fat infiltration, especially in deep, small or specially located muscles, showing high sensitivity, demonstrating the potential application of this method in local muscle mass monitoring and early non-invasive diagnosis.