To develop and validate a model for predicting intensive care unit (ICU) mortality risk in patients with malignant tumors complicated by acute respiratory failure (ARF) based on an explainable machine learning framework.

Reactive oxygen species (ROS) are major contributors to radiation therapy-induced side effects in cancer patients. A fusion antioxidant enzyme comprising glutathione S-transferase (GST), superoxide dismutase 1 (SOD1), and a transmembrane peptide has been shown to effectively mitigate ROS-induced damage. To enhance its targeting capability, the fusion protein was further modified by incorporating a matrix metalloproteinase-2/9 substrate peptide (X) and the transmembrane peptide R9, yielding the antioxidant enzyme GST-SOD1-X-R9 (GS1XR). This modification reduced its transmembrane ability in tumor cells, thereby selectively protecting normal cells from oxidative stress. However, the use of non-human GST poses potential immunogenicity risks. In this study, we employed seamless cloning technology to construct an expression vector containing the human GST gene to replace the non-human GST gene, and then expressed and purified novel fusion antioxidant enzymes GS1R and GS1XR. The protective effects of newly constructed GS1R and GS1XR against hydrogen peroxide (H₂O₂)-induced oxidative damage in L-02 cells were then evaluated using GS1 as a control. Enzymatic activity assays revealed that the specific activity of GST in GS1XR remained unchanged compared to the unmodified protein, while SOD activity was enhanced. Exposure to 200 μmol/L H₂O₂ transiently activated the nuclear factor-erythroid 2-related factor 2 (Nrf2) pathway; however, this activation diminished after 24 h, reducing cell viability to 48.4%. Both GS1R and GS1XR effectively scavenged intracellular ROS, directly counteracting oxidative stress and promoting Nrf2 nuclear translocation, thereby activating antioxidant pathways and restoring cell viability to normal levels. The two enzymes showed comparable efficacy. In contrast, GS1, lacking transmembrane capability, was restricted to scavenging extracellular ROS and provided only limited protection. In conclusion, both novel fusion antioxidant enzymes demonstrated significant potential in safeguarding normal cells from ROS-mediated oxidative damage. The findings provide a foundation for further investigation in related field.
Humans ; Oxidative Stress/drug effects* ; Hydrogen Peroxide ; Antioxidants/metabolism* ; Glutathione Transferase/metabolism* ; Recombinant Fusion Proteins/pharmacology* ; Superoxide Dismutase-1 ; Reactive Oxygen Species/metabolism* ; Superoxide Dismutase/biosynthesis*

[Objective]To explore the six medicinal ingredients,namely"(臧)Zangdu,Luru,Shashen,Baishashen,Shuchong and Fangji(ji)",in the Wucheng Hanjian prescription,in order to restore their original appearance.[Methods]Through literature search and double evidence method,a large number of relevant papers and books were consulted,and the research results were compared and summarized.[Results]This prescription consists of twenty-six medicinal ingredients,and the methods of preparation are diverse."(臧)Zangdu"should be"Daizhe"used by modern people;"Shashen"should be"Nanshashen",and"Baishashen"should be"Beishashen";"Shuchong"should be"Zhechong";there are two possible specific medicinal ingredients for"Luru",one is"Qucao",and the other is"lvru";"Fangji(ji)"should be"Fangkui".This prescription is used to treat"cold and dampness epidemic"with the etiology of cold and dampness,the main symptoms of constipation,coughing,and body pain,and the pathogenesis of external cold,internal drinking,and heat stagnation.[Conclusion]The research and restoration of the true appearance of the Wucheng Hanjian prescription is not only beneficial for further exploring the development process of traditional medicine,but also has practical reference significance for modern research on Chinese medicine,and also has certain value for the tracing research of Zhe school of traditional Chinese medicine.

Objective Analyze and compare the therapeutic value of contrast-enhanced ultrasound (CEUS) and enhanced spiral CT in patients with primary hepatocellular carcinoma (PHC) undergoing transcatheter arterial chemoembolization (TACE). Methods A retrospective analysis was conducted on 108 PHC patients (122 lesions) treated at Beijing Shijitan Hospital affiliated with Capital Medical University from July 2021 to June 2023. All patients were treated with TACE. After treatment, CEUS and contrast-enhanced spiral CT examinations were performed to evaluate the inactivation status of tumor lesions, with pathological results as the gold standard. The receiver operating characteristic curve and decision tree model were used to comprehensively evaluate the diagnostic value of CEUS, contrast-enhanced spiral CT, and their combination in PHC. Results The pathological results showed that 79 lesions remained active (positive) and 43 lesions were completely inactivated (negative). The areas under the receiver operating characteristic curve for evaluating PHC treatment efficacy by CEUS, contrast-enhanced spiral CT, and their combination were 0.975, 0.918, and 0.994, respectively. The sensitivity, positive predictive value, and actual application accuracy of CEUS and the combined method were higher than those of contrast-enhanced spiral CT (P < 0.05). A decision tree diagnostic model for PHC treatment efficacy was constructed using CEUS, contrast-enhanced spiral CT, and their combination as independent variables and PHC treatment efficacy as the dependent variable. The misjudgment rates were 3.3%, 10.7%, and 0.8%, respectively, and the prediction accuracy was 96.7%, 89.3%, and 99.2%, respectively. Conclusions CEUS and the combination of CEUS and contrast-enhanced spiral CT have high evaluation value for PHC treatment efficiency.

Objective Analyze and compare the therapeutic value of contrast-enhanced ultrasound (CEUS) and enhanced spiral CT in patients with primary hepatocellular carcinoma (PHC) undergoing transcatheter arterial chemoembolization (TACE). Methods A retrospective analysis was conducted on 108 PHC patients (122 lesions) treated at Beijing Shijitan Hospital affiliated with Capital Medical University from July 2021 to June 2023. All patients were treated with TACE. After treatment, CEUS and contrast-enhanced spiral CT examinations were performed to evaluate the inactivation status of tumor lesions, with pathological results as the gold standard. The receiver operating characteristic curve and decision tree model were used to comprehensively evaluate the diagnostic value of CEUS, contrast-enhanced spiral CT, and their combination in PHC. Results The pathological results showed that 79 lesions remained active (positive) and 43 lesions were completely inactivated (negative). The areas under the receiver operating characteristic curve for evaluating PHC treatment efficacy by CEUS, contrast-enhanced spiral CT, and their combination were 0.975, 0.918, and 0.994, respectively. The sensitivity, positive predictive value, and actual application accuracy of CEUS and the combined method were higher than those of contrast-enhanced spiral CT (P < 0.05). A decision tree diagnostic model for PHC treatment efficacy was constructed using CEUS, contrast-enhanced spiral CT, and their combination as independent variables and PHC treatment efficacy as the dependent variable. The misjudgment rates were 3.3%, 10.7%, and 0.8%, respectively, and the prediction accuracy was 96.7%, 89.3%, and 99.2%, respectively. Conclusions CEUS and the combination of CEUS and contrast-enhanced spiral CT have high evaluation value for PHC treatment efficiency.

Objective To investigate the clinical application value of wrist joint ulnar deviation supination 45° palmar oblique posi-tion in the diagnosis of scaphoid waist fracture and displacement.Methods The imaging and clinical data such as digital radiography(DR),CT of 93 wrist joint trauma patients were analyzed.The four position views including wrist joint anteroposterior+lateral view,scaphoid position,wrist joint ulnar deviation supination 45° palmar oblique position,scaphoid position+wrist joint ulnar devia-tion supination 45° palmar oblique position were analyzed by three readers.The consistency of the evaluation among different readers and the diagnostic efficiency of the diagnosis of scaphoid fracture and displacement were compared.Results The inter-observer agreement,sensitivity,specificity,accuracy,and other diagnostic efficiency of scaphoid waist fracture and displacement was evaluated,wrist joint ulnar deviation supination 45° palmar oblique position+scaphoid position and wrist joint ulnar deviation supination 45° palmar oblique position were better than those of scaphoid position and wrist joint anteroposterior+lateral view.The combination of wrist joint ulnar deviation supination 45° palmar oblique position+scaphoid position obtained the best diagnostic efficiency.Conclusion The wrist joint ulnar deviation supination 45° palmar oblique position shows the long axis of the scaphoid,which has a high diagnostic efficiency in the diagnosis of scaphoid waist fracture and displacement and would be used as a useful supplement to other scaphoid imaging.

Objective To investigate the changes of cortical thickness in patients with insomnia disorder(ID).Methods High-resolution MRI data were collected from 32 ID patients(ID group)and 30 healthy controls(HC)(HC group).The cortical thickness of both groups were analyzed using statistical parametric mapping 12(SPM12)software,while considering age,gender,and educational level as covariates.The cortical thickness in brain regions showed statistically significant differences was extracted for Pearson's correla-tion analyses with sleep and mood-related scales.Results Compared with the HC group,the ID group exhibited significantly decreased cortical thickness in brain regions such as the left insula,fusiform gyrus,orbitofrontal lobe,superior temporal gyrus,middle temporal gyrus,lateral occipital lobe and right caudal anterior cingulate gyrus[P＜0.05,family-wise error(FWE)correction].Furthermore,reduced cortical thickness of the cingulate gyrus was negatively correlated with the Pittsburgh sleep quality index(PSQI)score(r=-0.437,P=0.012).Conclusion The cortical thickness of several brain regions associated with sleep and mood are significantly reduced in patients with ID,providing potential neuroimaging evidence for understanding the pathophysiological mechanism of ID.

Objective To observe the drainage pathways of interstitial fluid(ISF)and substance clearance pattern in rat brain with fluorescence tracing imaging and treacer-based MRI.Methods Thirty-three male SD rats were randomly divided into fluorescence tracing group(F group,n=18)and treacer-based MRI group(MRI group,n=15),then further divided into thalamic,hippocampal and caudate nucleus subgroups,respectively.Evans blue was injected to rats in F group,and cardiac perfusion was performed after injection,then brain tissue was harvested,and frozen sections were made to observe the drainage pathways of IFS in different subgroups.MRI was performed on rats in MRI group before and after injection of gadolinium-diethylenetriamine pentaacetic acid(Gd-DTPA)to observe signal intensity in ROI of brain regions in different subgroups,the signal unit ratio was calculated,and the changing trend was explored.Results ISF in thalamus,hippocampus and caudate nucleus had different dominant drainage pathways,and the time of tracer reached to adjacent brain regions and whole brain in F group were different.In MRI group,within 4 h after injection of Gd-DTPA,there were differences in direction and clearance rate among tracer in thalamus,hippocampus and caudate nucleus,mainly manifesting as the tracer in thalamus and hippocampus drained to the ipsilateral cortex and lateral ventricle,while the tracer in the caudate nucleus diffused to the cortex and midbrain,and there were differences of the peak time of tracer signal among adjacent drainage brain regions.Conclusion Fluorescence and MR dual-mode imaging showed that there were differences in the dominant drainage pathways of IFS and clearance rates of small molecule substances among hypothalamus,hippocampus and caudate nucleus of rats.

Objective To observe the impact of ultrasonic image quality on the consistency of artificial intelligence(Al)assisted diagnosis system and manual measurements of biological indicators of developmental dysplasia of hip(DDH).Methods Hip ultrasonic data of 75 DDH and 345 non-DDH children were retrospectively analyzed,and the quality of ultrasonic images were subjectively scored.An evaluation model of ultrasonic image quality was constructed based on 140 ultrasonic images acquired from 140 cases(group A,containing 25 DDH and 115 non-DDH)using entropy weighting method,the weight of anatomic structures and impact factors related to DDH were obtained.The comprehensive image quality scores of other ultrasonic images acquired from 280 cases(group B,including 50 DDH and 230 non-DDH)were calculated,and the images in group B were classified into grade A,B and C in descending order.The consistency of AI and manual measurements of DDH biological indicators in group B was assessed.Results The weight of each anatomic structure and impact factors of DDH obtained with the model were as follows:The lower edge of iliac branch＞ilium＞glenoid labrum＞bony margin＞femoral head＞motion artifacts.In group B,grade A was observed in 67(9 DDH and 58 non-DDH),grade B was found in 160(26 DDH and 134 non-DDH),while grade C was noticed in 53(15 DDH and 38 non DDH)images.Except for β,femoral head coverage(FHC)and femoral head length diameter,the consistencies between AI and manual measurements of other indicators of DDH were grade A＞B＞C.In group B,AI and manual measurements were more consistent in DDH than in non-DDH cases.Conclusion Ultrasonic image quality affected the consistency between AI and manual measurements of biological indicators of DDH.When image quality was not good enough,further attention should be paid to measurement of FHC and sizes of femoral head.

Objective:Exploring the role and mechanism of gremlin-1 in lipotoxicity-mediated pancreatic β-cell dysfunction.Methods:The model of lipid toxicity-mediated pancreatic β-cell dysfunction was constructed using palmitic acid(PA) to treat mouse pancreatic β-cells(MIN6). Initially, to clarify the effects of lipotoxicity on islet β-cells, the cellular lipid deposition and changes in the levels of insulin caused by PA were detected. The effects of PA on gremlin-1 expression and its downstream signaling pathway BMPs/Smads were further investigated using qPCR and Western Blot assay. Subsequently, recombinant mouse gremlin-1 protein and BMP signaling pathway inhibitor LDN193189 were used to intervene the cells to explore the effects of gremlin-1 and its downstream signaling pathway BMPs/Smads on pancreatic islet β-cells.Results:PA could reduce pancreatic β-cell viability and insulin secretion capacity( P<0.05). Meanwhile, PA inhibited the expression and secretion of cell gremlin-1 and upregulated BMP-4 and its downstream Smad-1 and Smad-5( P<0.05). Intervention of cells with recombinant mouse gremlin-1 protein resulted in a significant elevation of insulin secretion and a concomitant decrease in the expression of key molecules in the BMP4/Smads signaling pathway( P<0.05). And inhibition of the BMP4/Smads signaling pathway ameliorated PA-induced pancreatic β-cell dysfunction. Conclusion:Gremlin-1 is involved in the regulation of lipotoxicity-mediated pancreatic islet β-cell dysfunction, and this effect may be associated with activation of BMP4/Smads signaling pathway.