1.Construction of a decision tree model for the severity of optic nerve injury in patients with primary open-angle glaucoma based on the levels of interleukin-6 and interleukin-2 in aqueous humor
Gaojun HE ; Xiaofeng XU ; Mingjiang LI
International Eye Science 2025;25(3):384-389
AIM: To investigate the relationship between the levels of interleukin-6(IL-6)and IL-2 in aqueous humor and the severity of optic nerve injury in patients with primary open-angle glaucoma(POAG), and to construct a decision tree model for the severity of optic nerve injury in POAG patients.METHODS: A prospective study was conducted on 107 patients(107 eyes)with POAG who were admitted to the hospital from May 2021 to October 2023. According to the mean defect(MD)value, the degree of optic nerve injury was judged and divided into three groups: mild, moderate and severe. The general data, IL-6 and IL-2 levels in aqueous humor of patients with different severity of optic nerve injury were compared, and the correlation between the levels of IL-6 and IL-2 in aqueous humor and the severity of optic nerve injury in POAG patients was analyzed. Multivariate Logistic regression analysis was used to test the influencing factors of the severity of optic nerve injury in POAG patients, and the decision tree model was constructed based on influencing factors.RESULTS: The proportion of patients with hypertension, intraocular pressure and binocular intraocular pressure difference in the severe group was higher than that in the mild and moderate groups, and the levels of IL-6 and IL-2 in the aqueous humor were significantly lower than those in the mild and moderate groups(all P<0.05). The levels of IL-6 and IL-2 in aqueous humor of POAG patients were negatively correlated with the severity of optic nerve injury(r=-0.361, -0.358, all P<0.001). Hypertension, intraocular pressure, binocular intraocular pressure difference, IL-6 and IL-2 levels in aqueous humor were independent factors affecting the degree of optic nerve injury in POAG patients(all P<0.05). Based on the above factors, a decision tree model was constructed, and three explanatory variables of IL-6, IL-2 levels in aqueous humor and hypertension were screened out. Among them, IL-2 level in aqueous humor was the most important root node variable and the most important predictor. The AUC of the decision tree model was 0.710(95% CI: 0.599-0.820, P=0.001), the sensitivity was 0.581, the specificity was 0.737, and the Youden index was 0.318, with a high predictive value.CONCLUSION: The levels of IL-6 and IL-2 in aqueous humor were significantly correlated with the severity of optic nerve injury in POAG patients. The decision tree model based on hypertension, intraocular pressure, binocular intraocular pressure difference, IL-6 and IL-2 levels in aqueous humor has a high evaluation value for the severity of optic nerve injury in POAG patients.
2.Construction of a decision tree model for the severity of optic nerve injury in patients with primary open-angle glaucoma based on the levels of interleukin-6 and interleukin-2 in aqueous humor
Gaojun HE ; Xiaofeng XU ; Mingjiang LI
International Eye Science 2025;25(3):384-389
AIM: To investigate the relationship between the levels of interleukin-6(IL-6)and IL-2 in aqueous humor and the severity of optic nerve injury in patients with primary open-angle glaucoma(POAG), and to construct a decision tree model for the severity of optic nerve injury in POAG patients.METHODS: A prospective study was conducted on 107 patients(107 eyes)with POAG who were admitted to the hospital from May 2021 to October 2023. According to the mean defect(MD)value, the degree of optic nerve injury was judged and divided into three groups: mild, moderate and severe. The general data, IL-6 and IL-2 levels in aqueous humor of patients with different severity of optic nerve injury were compared, and the correlation between the levels of IL-6 and IL-2 in aqueous humor and the severity of optic nerve injury in POAG patients was analyzed. Multivariate Logistic regression analysis was used to test the influencing factors of the severity of optic nerve injury in POAG patients, and the decision tree model was constructed based on influencing factors.RESULTS: The proportion of patients with hypertension, intraocular pressure and binocular intraocular pressure difference in the severe group was higher than that in the mild and moderate groups, and the levels of IL-6 and IL-2 in the aqueous humor were significantly lower than those in the mild and moderate groups(all P<0.05). The levels of IL-6 and IL-2 in aqueous humor of POAG patients were negatively correlated with the severity of optic nerve injury(r=-0.361, -0.358, all P<0.001). Hypertension, intraocular pressure, binocular intraocular pressure difference, IL-6 and IL-2 levels in aqueous humor were independent factors affecting the degree of optic nerve injury in POAG patients(all P<0.05). Based on the above factors, a decision tree model was constructed, and three explanatory variables of IL-6, IL-2 levels in aqueous humor and hypertension were screened out. Among them, IL-2 level in aqueous humor was the most important root node variable and the most important predictor. The AUC of the decision tree model was 0.710(95% CI: 0.599-0.820, P=0.001), the sensitivity was 0.581, the specificity was 0.737, and the Youden index was 0.318, with a high predictive value.CONCLUSION: The levels of IL-6 and IL-2 in aqueous humor were significantly correlated with the severity of optic nerve injury in POAG patients. The decision tree model based on hypertension, intraocular pressure, binocular intraocular pressure difference, IL-6 and IL-2 levels in aqueous humor has a high evaluation value for the severity of optic nerve injury in POAG patients.
3.USP25 ameliorates vascular remodeling by deubiquitinating FOXO3 and promoting autophagic degradation of FOXO3.
Yanghao CHEN ; Bozhi YE ; Diyun XU ; Wante LIN ; Zimin FANG ; Xuefeng QU ; Xue HAN ; Wu LUO ; Chen CHEN ; Weijian HUANG ; Hao ZHOU ; Gaojun WU ; Yi WANG ; Guang LIANG
Acta Pharmaceutica Sinica B 2025;15(3):1643-1658
Long-term hypertension causes excessive vascular remodeling and leads to adverse cardiovascular events. Balance of ubiquitination and deubiquitination has been linked to several chronic conditions, including pathological vascular remodeling. In this study, we discovered that the expression of ubiquitin-specific protease 25 (USP25) is significantly up-regulated in angiotensin II (Ang II)-challenged mouse aorta. Knockout of Usp25 augments Ang II-induced vascular injury such as fibrosis and endothelial to mesenchymal transition (EndMT). Mechanistically, we found that USP25 interacts directly with Forkhead box O3 (FOXO3) and removes the K63-linked ubiquitin chain on the K258 site of FOXO3. We also showed that this USP25-mediated deubiquitination of FOXO3 increases its binding to light chain 3 beta isoform and autophagosomic-lysosomal degradation of FOXO3. In addition, we further validated the biological function of USP25 by overexpressing USP25 in the mouse aorta with AAV9 vectors. Our studies identified FOXO3 as a new substrate of USP25 and showed that USP25 may be a potential therapeutic target for excessive vascular remodeling-associated diseases.
4.Deubiquitinase USP13 alleviates doxorubicin-induced cardiotoxicity through promoting the autophagy-mediated degradation of STING.
Liming LIN ; Jibo HAN ; Diyun XU ; Zimin FANG ; Bozhi YE ; Jinfu QIAN ; Xue HAN ; Julian MIN ; Xiaohong LONG ; Gaojun WU ; Guang LIANG
Acta Pharmaceutica Sinica B 2025;15(5):2545-2558
Doxorubicin (Dox) is an anthracycline drug widely applied in various malignancies. However, the fatal cardiotoxicity induced by Dox limits its clinical application. Post-transcriptional protein modification via ubiquitination/deubiquitination in cardiomyocytes mediates the pathophysiological process in Dox-induced cardiotoxicity (DIC). In this study, we aimed to clarify the regulatory role and mechanism of a deubiquitinating enzyme, ubiquitin-specific peptidase 13 (USP13), in DIC. RNA-seq analysis and experimental examinations identified that cardiomyocyte-derived USP13 positively correlated with DIC. Mice with cardiac-specific deletion of USP13 were subjected to Dox modeling. Adeno-associated virus serotype 9 (AAV9) carrying cTNT promoter was constructed to overexpress USP13 in mouse heart tissues. Cardiomyocyte-specific knockout of USP13 exacerbated DIC, while its overexpression mitigated DIC in mice. Mechanistically, USP13 deubiquitinates the stimulator of interferon genes (STING) and promotes the autolysosome-related degradation of STING, subsequently alleviating cardiomyocyte inflammation and death. Our study suggests that USP13 serves a cardioprotective role in DIC and indicates USP13 as a potential therapeutic target for DIC treatment.
5.Early Assessment of Right Heart Function in Patients with Left Heart Assist Device Implantation Based on Ultrasound Tissue-Tracking Strain Technique
Shujiao JI ; Gaojun XU ; Yingchun GUO ; Haohui ZHU
Chinese Journal of Medical Imaging 2025;33(6):633-637,680
Purpose To evaluate right ventricular function before and after the implantation of left ventricular assist device(LVAD)based on ultrasound tissue-tracking strain technique.Materials and Methods We collected data from 15 patients who underwent LVAD surgery from September 2021 to December 2023 in Henan Provincial Chest Hospital.A retrospective analysis was performed on various parameters,including right ventricular free wall strain,right ventricular global longitudinal strain,right ventricular fractional area change,tricuspid annular plane systolic excursion,tricuspid annulus motion spectrum S'peak and intracardiac structural changes,both before surgery and at 1 and 3 months post-surgery.Results Among the 15 LVAD patients,the surgical success rate was 93%.One patient died from acute heart failure following implantation,while the remaining 14 patients recovered well post-surgery.In the 14 patients,the right ventricular free wall strain gradually decreased in the basal,middle and apical segments both before and after surgery,with a more significant reduction in the apical segment.Specifically,the strain decreased at 1 and 3 months post-surgery compared to before surgery[15.80(7.00),8.47(4.90),12.00(5.20)],and showed a significant increase at 3 months post-surgery compared to 1 month post-surgery(all P<0.05).Additionally,the tricuspid annulus displacement of the right ventricle decreased post-surgery(P<0.05).Notably,the size of the left atrium and ventricle significantly decreased at 1 and 3 months post-surgery compared to before surgery,with statistical significance(P<0.05).Meanwhile,the right ventricular fractional area change and the size of the right ventricle was slightly larger than pre-surgery values,without statistical significance(P>0.05).There was no statistically significant change in left ventricular ejection fractions before and after surgery(P>0.05).Conclusion Right ventricular function decreases after LVAD surgery,gradually improving after 3 months,and changes in right ventricular free wall strain parameters are more sensitive.
6.Early Assessment of Right Heart Function in Patients with Left Heart Assist Device Implantation Based on Ultrasound Tissue-Tracking Strain Technique
Shujiao JI ; Gaojun XU ; Yingchun GUO ; Haohui ZHU
Chinese Journal of Medical Imaging 2025;33(6):633-637,680
Purpose To evaluate right ventricular function before and after the implantation of left ventricular assist device(LVAD)based on ultrasound tissue-tracking strain technique.Materials and Methods We collected data from 15 patients who underwent LVAD surgery from September 2021 to December 2023 in Henan Provincial Chest Hospital.A retrospective analysis was performed on various parameters,including right ventricular free wall strain,right ventricular global longitudinal strain,right ventricular fractional area change,tricuspid annular plane systolic excursion,tricuspid annulus motion spectrum S'peak and intracardiac structural changes,both before surgery and at 1 and 3 months post-surgery.Results Among the 15 LVAD patients,the surgical success rate was 93%.One patient died from acute heart failure following implantation,while the remaining 14 patients recovered well post-surgery.In the 14 patients,the right ventricular free wall strain gradually decreased in the basal,middle and apical segments both before and after surgery,with a more significant reduction in the apical segment.Specifically,the strain decreased at 1 and 3 months post-surgery compared to before surgery[15.80(7.00),8.47(4.90),12.00(5.20)],and showed a significant increase at 3 months post-surgery compared to 1 month post-surgery(all P<0.05).Additionally,the tricuspid annulus displacement of the right ventricle decreased post-surgery(P<0.05).Notably,the size of the left atrium and ventricle significantly decreased at 1 and 3 months post-surgery compared to before surgery,with statistical significance(P<0.05).Meanwhile,the right ventricular fractional area change and the size of the right ventricle was slightly larger than pre-surgery values,without statistical significance(P>0.05).There was no statistically significant change in left ventricular ejection fractions before and after surgery(P>0.05).Conclusion Right ventricular function decreases after LVAD surgery,gradually improving after 3 months,and changes in right ventricular free wall strain parameters are more sensitive.
7.Effectiveness and safety of the home-made umbrella-shaped Octoparms inferior vena cava filter in the prevention of pulmonary embolism
Boxiang ZHAO ; Jianlong LIU ; Gaojun TENG ; Caifang NI ; Hao XU ; Zhen LI ; Shuiting ZHAI ; Yanrong ZHANG ; Hua XIANG ; Weizhu YANG ; Jianping GU
Chinese Journal of Radiology 2022;56(5):556-562
Objective:To evaluate the effectiveness and safety of the home-made umbrella-shaped Octoparms inferior vena cava filter in the prevention of pulmonary embolism.Methods:A multicenter, randomized, positive parallel controlled, non-inferiority clinical trial was conducted in ten hospitals in China from October 2017 to March 2019. A total of 188 subjects were enrolled according to the same inclusion and exclusion criteria in different institutes. The 188 subjects were randomly divided into the trial group or the control group according to 1∶1 by the central randomization system, with 94 cases in each group. Octoparms inferior vena cava filter was used in the trial group, and the Celect inferior vena cava filter in the control group. The primary effective index was clinical success rate,including the clinical success rate of filter placement and filter retrieval. The secondary index included the rate of manual success of the delivery sheath system,incidence of pulmonary embolism(within 6 months), incidence of filter fracture,migration (>20 mm),tilt(>15°) on insertion/retrieval,and the situation of inferior vena cava flow(within 6 months). Safety evaluation included the incidence of filter related complications and device-related adverse events immediately after surgery and during follow-up.Results:The success rate of implantation was 100% in 188 subjects. Filter retrieval was performed in 87 cases (92.55%) in the trial group and 91 cases (96.81%) in the control group. The clinical success rate of the trial group was 97.87%(92/94) and that of the control group 98.94%(93/94). There was no significant difference between the two groups (χ 2=0.77, P=0.380). The success rate of delivery sheath system was 96.81%(91/94) and 98.94%(93/94) in the trail group and the control group,respectively. There was no significant difference between the two groups( P=0.621). There was 1 case (1.22%) of new asymptomatic pulmonary embolism in the trial group after filter placement and 2 cases (2.44%) in the control group. There was no significant difference between the two groups ( P>0.05). No filter fracture or migration (>20 mm) occurred in either group. The tilting of filter (>15°) was found in 1 case (1.06%) in the test group and 1 case (1.06%) in the control group when the filter was placed. The tilting of filter (>15°) was found in 0 case in the test group and 2 cases (2.44%) in the control group when the filter was retrieved. There was no significant difference between the two groups ( P>0.05). Inferior vena cava thrombosis before filter retrieval was found in 5 cases (5.75%) in trial group and 3 cases (3.30%) in control group. There was no significant difference between the two groups ( P=0.489). There were no immediate serious complications during filter placement/removal in either group. No filter obstruction,migration,deformation,penetration and occlusion of inferior vena cava. The incidence of device-related adverse events was low in both group. There was no significant difference between the two groups ( P>0.05). Conclusion:The home-made umbrella-shaped Octoparms inferior vena cava filter is effective and safe in preventing pulmonary embolism, and is not worse than Celect filter.
8.Expression and significance of granulocyte colony-stimulating factor and granulocyte- macrophage colony-stimulating factor in patients with acute respiratory distress syndrome
Gaojun XU ; Youzu XU ; Shanshan CHEN
Chinese Journal of Primary Medicine and Pharmacy 2021;28(6):860-864
Objective:To investigate the expression and significance of granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF) in patients with acute respiratory distress syndrome (ARDS).Methods:The clinical data of 81 patients with ARDS who received treatment between February 2018 and July 2020 in Linhai Second People's Hospital, China (group A) and 69 healthy controls who concurrently received physical examination (group B) were retrospectively analyzed. Serum levels of G-CSF, GM-CSF and oxygenation index (OI) measured before treatment in the group A were compared with the levels measured in the control group. Serum levels of G-CSF and GM-CSF measured before treatment were compared between patients with different disease severities in the group A. The correlation between serum G-CSF and GM-CSF levels and disease condition was analyzed. The significance of serum G-CSF and GM-CSF levels in the diagnosis of ARDS was investigated.Results:Before treatment, serum G-CSF and GM-CSF levels in the group A were (201.89 ± 19.44) ng/L, (48.95 ± 6.03) ng/L, respectively, which were significantly higher than those in the group B [(38.13 ± 5.22) ng/L, (7.71 ± 0.92) ng/L, t = 67.889, 56.228, both P < 0.001]. OI in the group A was significantly lower than that in the group B [(159.09 ± 16.81) mmHg vs. (385.13 ± 20.34) mmHg, t = 74.519, P < 0.001). In group A, serum levels of G-CSF and GM-CSF were (271.99 ± 23.15) ng/L and (65.07 ± 8.38) ng/L respectively in patients with severe acute respiratory distress syndrome ( n = 13), (203.14 ± 18.36) ng/L and (50.91 ± 7.18) ng/L respectively in patients with moderate acute respiratory distress syndrome ( n = 30), and (176.92 ± 15.98) ng/L and (41.89 ± 6.02) ng/L, respectively in patients with mild acute respiratory distress syndrome ( n = 38). There was significant difference among patients with severe, moderate and mild acute respiratory distress syndrome ( F = 133.201, 57.116, both P < 0.05). Serum levels of G-CSF and GM-CSF in group A were negatively correlated with OI ( r = -0.819, -0.824, both P < 0.05). The area under the receiver operating characteristic curve of serum levels of G-CSF and GM-CSF and their combination were 0.780 (95% CI: 0.628-0.933), 0.752 (95% CI: 0.590-0.913) and 0.912 (95% CI: 0.835-0.989), respectively. The Youden index was 0.686, 0.696 and 0.739, respectively. The area under the receiver operating characteristic curve and the Youden index of the combined detection of serum levels of G-CSF and GM-CSF were highest. Conclusion:Serum levels of G-CSF and GM-CSF in patients with ARDS were higher than those in healthy controls. Higher serum levels of G-CSF and GM-CSF led to more severe disease condition. Serum levels of G-CSF and GM-CSF in combination has a higher value in the diagnosis of ARDS than serum levels of G-CSF and GM-CSF alone.
10.The clinical application of percutaneous puncturing drainage in treating bacterial liver abscess
Sheng XU ; Haidong ZHU ; Li CHEN ; Haifeng ZHOU ; Gaojun TENG
Journal of Interventional Radiology 2018;27(2):181-185
Bacterial liver abscess is a rare and life-threatening disease, and, clinically, its incidence has gradually increased in recent years. In terms of its treatment, percutaneous puncturing drainage combined with antibiotics has been the first-line therapeutic means, and surgical procedures are often used for patients in whom the interventional drainage is ineffective or in whom the liver abscess is complicated by abdominal disease that needs surgical management. Percutaneous catheter drainage and percutaneous fine needle aspiration, regarded as the two most commonly used interventional drainage methods, have been widely employed in the treatment of bacterial liver abscess; and percutaneous catheter drainage is more commonly adopted in clinical practice. Although the prognosis of bacterial liver abscess has been improved significantly, there is still a certain fatality rate. There is still no a well-accepted consensus on treatment guidelines. Moreover, there are still many controversies over the indications of percutaneous puncturing drainage. Based on a comprehensive review of the domestic and foreign literature, this paper aims to make a detailed introduction concerning percutaneous puncturing drainage for the treatment of bacterial liver abscess, focusing on its development history, curative effect and prognosis, and, in order to guide the clinical practice, the principles of the use of antibiotics, the comparison of clinical effect with surgery and the therapeutic indications will be also discussed.

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