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.

Objective: To investigate the effects of grain size and immersion dyeing time on the dye penetration depth and color parameters of zirconia, and analyze the dyeing behavior in relation to the material's pore characteristics to provide experimental evidence for developing personalized immersion staining protocols for clinical applications targeting zirconia with different microstructures. Methods: A total of 135 pre-sintered zirconia specimens with three different grain sizes were fabricated using computer aided design/manufacturing technology and divided into three groups (S1, S2, S3; n=45). Randomly select 6 specimens from each group, among which 3 zirconia pre sintered specimens are soaked in 10 mL A2 staining solution for 60 s, dried and sintered, and the other 3 are not treated. Observe the microstructure of the outer surface and bonding surface of the specimen under SEM, and use Image J software to count and measure the grain size. From each group, three randomly selected specimens were subjected to mercury intrusion porosimetry to analyze porosity and pore size distribution. For the remaining specimens, the bottom surface (10 × 10 mm) was designated as the staining surface and immersed in 10 mL of A2 staining liquid. The remaining specimens were stained at six time gradients (10, 20, 30, 60, 90, 120 s). After staining, half of the specimens were sectioned perpendicular to the stained surface and fully sintered to measure the staining penetration depth. The other half were directly fully sintered. A spectrophotometer was used to measure the color parameters (L*, a*, b*) of the stained surface, and the color difference (ΔE00) relative to a standard A2 shade tab was calculated. Results: The average grain sizes (G) for the three groups were GS1=(221.64±62.16) nm, GS2=(197.80±46.72) nm, and GS3=(150.21±42.11) nm; the average porosities (P) were PS1=37.82%, PS2=46.02%, and PS3=47.36%. Both grain size and staining time significantly affected the staining outcome of zirconia (P<0.001), with a significant interaction effect (P<0.001). Staining penetration depth increased with prolonged staining time and decreased grain size (P<0.001). All fully sintered specimens exhibited a perceptible color difference (ΔE00>0.8) compared with the standard A2 shade tab (VITA, USA). Specifically, specimens from group S1 stained for 20 s, group S2 stained for 60 s, and group S3 stained for 10 s exhibited color differences below the clinically acceptable threshold (ΔE00<1.8), meeting clinical thickness requirements. Specimens stained for other time intervals exceeded the clinically acceptable color difference threshold (ΔE00>1.8). Conclusion The porosity of pre-sintered zirconia with different grain sizes varied. Higher porosity correlated with deeper staining penetration. The staining time required to achieve the standard A2 shade differed among zirconia materials with different grain sizes. In clinical applications, the immersion dyeing protocol for zirconia should be optimized based on the grain size and pore characteristics of zirconia with different grain sizes, so as to avoid color deviations caused by improper dyeing time.

Diterpenoid ferruginol is a key intermediate in biosynthesis of active ingredients such as tanshinone and carnosic acid.However, the traditional process of obtaining ferruginol from plants is often cumbersome and inefficient. In recent years, the increasingly developing gene editing technology has been gradually applied to the heterologous production of natural products, but the production of ferruginol in microbe is still very low, which has become an obstacle to the efficient biosynthesis of downstream chemicals, such as tanshinone. In this study, miltiradiene was produced by integrating the shortened diterpene synthase fusion protein,and the key genes in the MVA pathway were overexpressed to improve the yield of miltiradiene. Under the shake flask fermentation condition, the yield of miltiradiene reached about(113. 12±17. 4)mg·L~(-1). Subsequently, this study integrated the ferruginol synthase Sm CYP76AH1 and Sm CPR1 to reconstruct the ferruginol pathway and thereby realized the heterologous synthesis of ferruginol in Saccharomyces cerevisiae. The study selected the best ferruginol synthase(Il CYP76AH46) from different plants and optimized the expression of pathway genes through redox partner engineering to increase the yield of ferruginol. By increasing the copy number of diterpene synthase, CYP450, and CPR, the yield of ferruginol reached(370. 39± 21. 65) mg·L~(-1) in the shake flask, which was increased by 21. 57-fold compared with that when the initial ferruginol strain JMLT05 was used. Finally, 1 083. 51 mg·L~(-1) ferruginol was obtained by fed-batch fermentation, which is the highest yield of ferruginol from biosynthesis so far. This study provides not only research ideas for other metabolic engineering but also a platform for the construction of cell factories for downstream products.
Saccharomyces cerevisiae/genetics* ; Diterpenes/metabolism* ; Metabolic Engineering ; Fermentation ; Abietanes

The chemical composition of Paeoniae Radix Alba(PRA) is complex, with primary secondary metabolites including monoterpenoids, tannins, triterpenoids, and flavonoids. In previous studies on the material basis of PRA, it was found that, in addition to the widely studied characteristic monoterpene glycosides, tannic acid components also play an important role in the efficacy of PRA. However, their pharmacological effects have not been thoroughly investigated. This paper reviews the tannic acid components in PRA, including pentagaloyl glucose(PGG), tetragaloyl glucose(TGG), trigaloyl glucose(TriGG), and gallic acid, along with their structures, properties, and characteristics to provide a detailed discussion of their pharmacological activities and related mechanisms, aiming to offer a theoretical basis for the material basis research and clinical application of PRA.
Paeonia/chemistry* ; Tannins/chemistry* ; Humans ; Drugs, Chinese Herbal/chemistry* ; Animals ; Plant Extracts

PURPOSE: To investigate the protective effect of sub-hypothermic mechanical perfusion combined with membrane lung oxygenation on ischemic hypoxic injury of yorkshire brain tissue caused by traumatic blood loss. METHODS: This article performed a random controlled trial. Brain tissue of 7 yorkshire was selected and divided into the sub-low temperature anterograde machine perfusion group (n = 4) and the blank control group (n = 3) using the random number table method. A yorkshire model of brain tissue injury induced by traumatic blood loss was established. Firstly, the perfusion temperature and blood oxygen saturation were monitored in real-time during the perfusion process. The number of red blood cells, hemoglobin content, NA⁺, K⁺, and Ca²⁺ ions concentrations and pH of the perfusate were detected. Following perfusion, we specifically examined the parietal lobe to assess its water content. The prefrontal cortex and hippocampus were then dissected for histological evaluation, allowing us to investigate potential regional differences in tissue injury. The blank control group was sampled directly before perfusion. All statistical analyses and graphs were performed using GraphPad Prism 8.0 Student t-test. All tests were two-sided, and p value of less than 0.05 was considered to indicate statistical significance. RESULTS: The contents of red blood cells and hemoglobin during perfusion were maintained at normal levels but more red blood cells were destroyed 3 h after the perfusion. The blood oxygen saturation of the perfusion group was maintained at 95% - 98%. NA⁺ and K⁺ concentrations were normal most of the time during perfusion but increased significantly at about 4 h. The Ca²⁺ concentration remained within the normal range at each period. Glucose levels were slightly higher than the baseline level. The pH of the perfusion solution was slightly lower at the beginning of perfusion, and then gradually increased to the normal level. The water content of brain tissue in the sub-low and docile perfusion group was 78.95% ± 0.39%, which was significantly higher than that in the control group (75.27% ± 0.55%, t = 10.49, p < 0.001), and the difference was statistically significant. Compared with the blank control group, the structure and morphology of pyramidal neurons in the prefrontal cortex and CA1 region of the hippocampal gyrus were similar, and their integrity was better. The structural integrity of granulosa neurons was destroyed and cell edema increased in the perfusion group compared with the blank control group. Immunofluorescence staining for glail fibrillary acidic protein and Iba1, markers of glial cells, revealed well-preserved cell structures in the perfusion group. While there were indications of abnormal cellular activity, the analysis showed no significant difference in axon thickness or integrity compared to the 1-h blank control group. CONCLUSIONS Mild hypothermic machine perfusion can improve ischemia and hypoxia injury of yorkshire brain tissue caused by traumatic blood loss and delay the necrosis and apoptosis of yorkshire brain tissue by continuous oxygen supply, maintaining ion homeostasis and reducing tissue metabolism level.
Animals ; Perfusion/methods* ; Disease Models, Animal ; Brain Injuries/etiology* ; Swine ; Male ; Hypothermia, Induced/methods*

OBJECTIVE: To explore a predictive model that can better predict the prognosis of patients with diffuse large B-cell lymphoma (DLBCL), and validate its clinical value. METHODS: Clinical data of 134 newly treated DLBCL patients were collected from Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine from January 2015 to January 2020. Several risk factors of the patients were screened and analyzed, a novel prognostic model were then established based on this, and its clinical application potential was validated. RESULTS: In the novel model, predicting progression-free survival (PFS) based on the age at initial treatment, albumin level, Hans classification, Ann Arbor stage, and BCL2 expression showed better predictive performance than International Prognostic Index (IPI) score (AUC: 0.788 vs 0.620，P <0.001). Predicting overall survival (OS) based on the age at initial treatment, albumin level, lactate dehydrogenase (LDH) level, and expressions of BCL2 and MUM1 proteins also showed better predictive performance for mortality risk than IPI score (AUC: 0.817 vs 0.624，P <0.001). CONCLUSION This novel prognostic model can better predict the survival prognosis of DLBCL patients compared to the IPI scoring system.
Humans ; Lymphoma, Large B-Cell, Diffuse/diagnosis* ; Prognosis ; Proto-Oncogene Proteins c-bcl-2/metabolism* ; Risk Factors ; Male ; Female ; Middle Aged

This study aims to ensure the effectiveness of medical ultrasound diagnostic equipment in clinical applications by testing multiple key performance indicators using tissue-mimicking phantoms and exploring the changes in these performance indicators over time. Firstly, 17 in-service medical ultrasound diagnostic equipments were selected, and their depth of penetration, dead zone, lateral resolution, axial resolution, geometric position error, and cystic focal diameter error were tested according to the verification regulations. In addition, the study retrospectively analyzed the performance testing data of 19 medical ultrasound diagnostic equipments over the past three consecutive years and conducted statistical analysis. Through the testing, all performance indicators of the 17 equipments met the requirements of the verification regulations, indicating that they can stably and reliably provide high-quality ultrasound diagnostic images and data in clinical applications. Meanwhile, retrospective data showed that with the increase with the increase in service life, the resolving ability at the far field of the 19 equipments decreased, and the cystic focal diameter error increased. Therefore, it is recommended that medical institutions establish a regular testing and maintenance system for medical ultrasound diagnostic equipment, conducting regular performance evaluations and maintenance to ensure its good working condition.
Phantoms, Imaging ; Ultrasonography/instrumentation* ; Retrospective Studies

Objective To investigate the protective effect of benzoylaconine(BAC)on H9c2 cardio-myocytes after oxygen glucose deprivation/reoxyenation(OGD/R)injury.Methods After an in vitro model of OGD/R injury was established in H9c2 cells,the cells were treated with BAC at different concentrations(0,25,50,75,100 μmol/L)to determine its optimal dose.Then,H9c2 cells were randomly divided into control group,OGD/R group,OGD/R+BAC group(75 μmol),OGD/R+LY294002 group(PI3K/Akt inhibitor),and OGD/R+LY294002+BAC group.Corre-sponding reagent kits were used to determine cell viability and LDH level,as well as the expres-sion levels of TNF-α,IL-6,IL-1β,MDA and GSH-Px in the cells.Western blotting was applied to detect the expression of the PI3K/Akt pathway proteins,as well as autophagic proteins such as LC3,Beclin1,and P62.Results Compared to the control group,the cell viability was significantly decreased,and LDH level was obviously increased in the OGD/R group(P＜0.01).Treatment of 75 μmol/L BAC significantly increased the cell viability(0.87±0.06 vs 40.49±0.06,P＜0.01)and decreased the LDH level(86.75±7.79 U/L vs 234.42±6.20 U/L,P＜0.01)when compared to the levels of the OGD/R group.OGD/R injury induced notable increases in TNF-α,IL-6,IL-1β,and MDA expression levels,while decrease of GSH-Px expression level(P＜0.01),and down-regulation of p-PI3K,p-Akt and P62 and up-regulation of LC3 Ⅱ/LC3 Ⅰ and Beclin-1(P＜0.01)when compared with the control group.Treatment of 75 μmol/L BAC increased the levels of p-PI3K,p-Akt,and P62 proteins(0.90±0.07 vs 0.58±0.04,1.02±0.02 vs 0.49±0.01,1.48±0.05 vs 0.87±0.04)and decreased those of LC3 Ⅱ/LC3 Ⅰ and Beclin-1(0.52±0.01 vs 1.24±0.04,0.12±0.01 vs 0.32±0.02)when compared with the OGD/R group(P＜0.01).Conclusions BAC attenu-ates the inflammatory response and oxidative stress of myocardial cells after OGD/R injury,regu-lates autophagy homeostasis,and reduces myocardial cell damage.Its regulatory effect on myocar-dial autophagy homeostasis may be related to the activation of the PI3K/Akt pathway.

OBJECTIVE To explore the current status of surveillance data of nosocomial infections in a three-A hos-pital of Jiangsu Province and find out the problems in prevention and control of the nosocomial infection so as to provide scientific bases for formulating targeted prevention strategies.METHODS The related data of all infection cases from Changzhou First People's Hospital between 2014 and 2023 were exported from information real-time surveillance system and were analyzed by using Excel 2021 and R 4.3.2 software.RESULTS The average incidence rate of hospital-associated infection was 1.32％from 2014 to 2023,declining from 2.11％in 2014 to 0.97％in 2023,and it showed a downward trend(Z=-30.010,P＜0.001).The incidence rate of hospital-associated infec-tion was 19.86％in neurosurgery department(Z=-3.041,P=0.002),10.27％in hematology department(Z=5990,P＜0.001),8.85％in neurology department(Z=-1.437,P=0.151),7.00％in critical care medicine de-partment(Z=5.907,P＜0.001),6.28％in gastrointestinal surgery department(Z=-4.435,P＜0.001),thorac-ic surgery department(Z=1.696,P=0.090),4.52％in cardiothoracic surgery department(Z=13.218,P＜0.001),2.95％in oncology department(Z=9.064,P＜0.001).Among the patients with hospital-associated infec-tions,the patients with lower respiratory tract infection accounted for 46.71％(the highest),increasing from 34.94％to 51.67％(Z=12.532,P＜0.001),the patients with upper respiratory tract infection 10.37％(Z=-10.229,P＜0.001),the patients with urinary tract infection 6.92％(Z=1.489,P=0.137),the patients with urinary catheter-related infection 3.71％(Z=13.218,P=0.317).Totally 13,593 strains of pathogens were isola-ted,65.26％of which were gram-negative bacteria and did not show a significant changing trend,24.62％were gram-positive bacteria,and 10.12％were fungi;Klebsiella pneumoniae(15.76％)and Acinetobacter baumannii(15.34％)were the predominant species of the gram-negative bacteria;Staphylococcus aureus(8.37％)and Corynebacterium striatum(3.60％)were dominant among the gram-positive bacteria;Candida albicans(5.13％)and Candida tropicalis(0.96％)were the major species of the fungi.The percentage of central venous catheteriza-tion was the highest(27.04％)among the risk factors for the hospital-associated infection,increasing from 14.87％to 21.75％(Z=17.482,P＜0.001).CONCLUSIONS The control of hospital-associated infection has been made remarkable achievement.It is necessary to strengthen the construction of infection control team,push for-ward the whole process and delicacy management,normalize the use of antibiotics,reduce the unnecessary inva-sive procedures and shorten the duration of invasive operations so as to further improve the medical quality.