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 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 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 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.

Objective:To analyze clinical efficacy and safety of dermabrasion for the treatment of familial benign chronic pemphigus.Methods:Clinical data were retrospectively collected from 6 patients with familial benign chronic pemphigus, who underwent dermabrasion in the Department of Dermatology, the First Affiliated Hospital of Dalian Medical University from February 2019 to July 2020. There were 3 males and 3 females, they were aged from 39 to 65 years, and their disease duration ranged from 10 to 40 years. All the patients were postoperatively followed up for 14 - 34 months. Response rates were calculated, and adverse reactions and recurrence were observed.Results:Dermabrasion was performed on the 6 patients in 55 body areas. After operation, complete recovery was observed in 36 areas (65.5%), marked improvement was noted in 13 areas (23.6%), and moderate improvement was observed in 6 areas (10.9%) ; there were no areas with no response, resulting in an overall response rate of 89.1%. Postoperatively, the patients experienced no obvious discomfort, and only slight hypopigmentation and mild scars remained. During the follow-up of 14 to 34 months, no recurrence was observed in the treated areas.Conclusion:Dermabrasion was safe and effective for the treatment of familial benign chronic pemphigus.

Objective To explore the value of artificial intelligence federated learning system based on chest X-ray films for pathogen diagnosis of community-acquired pneumonia(CAP)in children.Methods Totally 900 cases of CAP children from 2 hospitals were retrospectively enrolled,including bacterial,viral and mycoplasma CAP(each n=300),and chest posteroanterior X-ray films were collected.Meanwhile,chest posteroanterior X-ray films of 5856 children from the publicly available dataset GWCMCx were collected,including 4273 CAP images and 1583 healthy chest images.All above 6756 images were divided into training set(n=5359)and validation set(n=1397)at the ratio of 8∶2.Then a pathogen diagnosis model of children CAP was established based on attention mechanism.Binary and ternary diagnostic algorithms were designed,and federated deployment training was performed.The efficacy of this system for pathogen diagnosis of children CAP was analyzed and compared with DenseNet model.Results Based on all data,the accuracy of the obtained artificial intelligence federated learning system model for diagnosing children CAP was 97.00%,with the area under the curve(AUC)of 0.990.Based on hospital data,the AUC of this system using single imaging data and clinical-imaging data for pathogen diagnosis of children CAP was 0.858 and 0.836,respectively,both better than that of DenseNet model(0.740,both P＜0.05).Conclusion The artificial intelligence federated learning system based on chest X-ray films could be used for pathogen diagnosis of children CAP.

Objective To observe the value of cardiac CT angiography(CCTA)for left atrial appendage closure(LAAC).Methods Twelve Labradors were enrolled and underwent LAAC.CCTA examinations were performed before and 7,45 and 90 days after LAAC,and the left atrial appendage(LAA)parameters before and post LAAC occluder compression ratio were recorded.Ninety days after LAAC,the dogs were euthanized for gross anatomical observation,micro CT imaging and pathological examination,and the value of CCTA for LAAC was analyzed.Results Based on CCTA before LAAC,LAA opening depth was(18.8±2.6)mm,the minimum diameter was(16.3±2.0)mm and the maximum diameter was(22.6±3.2)mm,so 28 mm diameter occluders were selected for LAAC.Seven,45 and 90 days after LAAC,no displacement of occluder,thrombi nor device leakage was found on CCTA,while no significant difference of compression ratio was found among different time points(P＞0.05),nor between those measured with CCTA and micro CT 90 days after LAAC(P＞0.05).Ninety days after LAAC,gross dissection revealed complete endothelialization of occlude in 11 dogs and incomplete endothelialization in 1 dog.Pathological examination showed that collagen fibers arranged neatly,with endothelial cells covering the surface,and no inflammatory cell infiltration was observed.Conclusion CCTA could be used to observe LAA and surrounding structures before LAAC,hence guiding to select appropriate occluder,evaluate occlusion effect and monitor complications of LAAC in dogs.