1.Praeruptorin A inhibits neutrophil inflammation through ferritin and its role in sepsis
Pengchao YU ; Hong ZHENG ; Yifan HU ; Zhouxin YANG ; Zejia YU ; Jinnan XIA ; Haiying HAN ; Dongyang GUO
Chinese Journal of Microbiology and Immunology 2025;45(3):248-255
Objective:To investigate the potential of praeruptorin A (PA) in alleviating inflammatory damage in sepsis through the inhibition of ferritin expression.Methods:C57BL/6 mice were intraperitoneally injected with lipopolysaccharide (LPS) to establish the model of sepsis. After 6 and 12 h of PA intervention, serum levels of inflammatory cytokines IL-6 and TNF-α were measured by ELISA. Kidney tissues were collected at 72 h for HE staining to assess inflammatory cell infiltration and tissue damage. Human neutrophils were divided into four groups: control, LPS, ferritin, and LPS+ ferritin groups. After 12 h of intervention, qRT-PCR was used to detect the expression of IL-6 and TNF-α mRNA. In order to observe the effect of PA on the expression of inflammatory cytokines and ferritin, human neutrophils were grouped into control, LPS, and LPS+ PA (2/3/4 μmol/L) groups. After 12 h of intervention, qRT-PCR was performed to measure the expression of IL-1β, IL-6, TNF-α, and ferritin mRNA; ELISA was used to quantify the levels of IL-1β, IL-6, and TNF-α in culture supernatants; Western blot was used to analyze the expression of ferritin. Molecular docking was conducted to verify interactions between PA and ferritin.Results:Significant inflammatory cell recruitment, tissue damage, and elevated serum levels of IL-6 and TNF-α ( P<0.01) were observed in mice with LPS-induced sepsis. PA significantly inhibited cytokine secretion ( P<0.01) and alleviated tissue injury in sepsis mice. In human neutrophil models, ferritin upregulated the expression of IL-6 and TNF-α mRNA ( P<0.01); LPS stimulation alone increased the expression of IL-1β, IL-6, TNF-α, and ferritin at both mRNA and protein levels ( P<0.01), while co-stimulation with PA (3/4 μmol/L) significantly reversed the aforementioned results ( P<0.01). Molecular docking confirmed there were interaction sites between PA and ferritin. Conclusion:PA inhibits the release of inflammatory cytokines and alleviates tissue damage in sepsis, and the potential mechanism may involve modulating ferritin expression to suppress inflammatory responses.
2.Construction of a prediction model for muscular invasion in upper urinary tract urothelial carcinoma based on preoperative MRI features
Haonan CHEN ; Lingkai CAI ; Hongyuan DING ; Hao JI ; Tianxiao HONG ; Hao YU ; Qikai WU ; Chaoran ZHAO ; Xiao YANG ; Qiang CAO ; Xiancheng ZHAO ; Pengchao LI ; Qiang LYU
Chinese Journal of Urology 2025;46(9):661-668
Objective:To construct a nomogram based on preoperative MRI imaging features for the prediction of muscle-invasive upper urinary tract urothelial carcinoma(UTUC)and evaluate its performance.Methods:This retrospective cohort study analyzed the clinical data of 99 UTUC patients treated at the First Affiliated Hospital of Nanjing Medical University from April 2018 to May 2024. Among them,69(69.7%)were male and 30(30.3%)were female,with a median age of 67.0 years. All patients underwent preoperative MRI and radical nephroureterectomy. According to postoperative pathology,tumors staged ≥ T 2 were assigned to the muscle-invasive group,and those staged ≤ T 1 were assigned to the non-muscle-invasive group. Baseline data,pathological information,and imaging characteristics were collected and compared between the two groups. Logistic regression analysis was performed to identify risk factors for muscle-invasive UTUC,and a nomogram was constructed. The diagnostic performance of the model was assessed using receiver operating characteristic(ROC)curves,calibration curves,and decision curve analysis(DCA). Results:Among the 99 patients,70(70.7%)were diagnosed with muscle-invasive UTUC,and 29(29.3%)with non-muscle-invasive UTUC. The muscle-invasive group had significantly larger tumor size[4.5(2.8,7.0)cm vs. 3.0(2.3,4.5)cm, P = 0.029],a higher incidence of multifocal tumors[37.1%(26/70)vs. 3.5%(1/29), P < 0.001],patchy tumors[30.0%(21/70)vs. 6.9%(2/29), P = 0.019],spiculated tumor margins[52.9%(37/70)vs. 17.2%(5/29), P = 0.001],tumor compression on renal parenchyma or periureteral/peripelvic fat[68.6%(48/70)vs. 10.3%(3/29), P < 0.001],high-grade pathology[92.9%(65/70)vs. 75.9%(22/29), P = 0.043],lymph node metastasis[28.6%(20/70)vs. 0, P = 0.001],and lymphovascular invasion[42.9%(30/70)vs. 10.3%(3/29), P=0.002]. The apparent diffusion coefficient(ADC)values[0.9(0.8,1.1)× 10 -3 mm2/s vs. 1.1(1.0,1.4)× 10 -3 mm2/s, P < 0.001]and normalized ADC(NADC)values[0.8(0.7,1.0)vs. 0.9(0.8,1.1), P = 0.002]were significantly lower in the muscle-invasive group. Univariate logistic regression identified multifocality,patchy tumor patterns,spiculated tumor margins,tumor compression on renal parenchyma or periureteral/peripelvic fat,and low NADC values as risk factors for muscle-invasive UTUC(all P < 0.05). Multivariate analysis revealed multifocality( OR = 17.903,95% CI 1.650 - 194.253, P = 0.018),tumor compression on renal parenchyma or perirenal / ureteral fat( OR = 14.690,95% CI 3.069 - 70.323, P < 0.001),and low NADC value( OR = 0.016,95% CI 0.001 - 0.471, P = 0.017)as independent risk factors. A nomogram was constructed based on these factors. The area under the ROC curve(AUC)of the model was 0.898(95% CI 0.838 - 0.957),with an optimal cutoff value of 0.639. The model showed an accuracy of 83.8%,sensitivity of 81.4%,and specificity of 89.7%. Calibration curves indicated good calibration,and DCA showed that the model provided substantial clinical net benefit. Conclusions:This study constructed a nomogram based on preoperative MRI features,including tumor multifocality,compression on renal parenchyma or periureteral/peripelvic fat and NADC value,which demonstrates good predictive performances for muscle-invasive UTUC.
3.Clinical efficacy of robot-assisted Wallace ileal conduit in the treatment of ureteral obstruction after radical cystectomy
Tianxiao HONG ; Chaoran ZHAO ; Rongjie BAI ; Pengchao LI
Journal of Modern Urology 2025;30(10):860-864
Objective To investigate the feasibility and efficacy of robot-assisted Wallace ileal conduit in the treatment of ureteral obstruction following radical cystectomy.Methods A retrospective analysis was conducted on the clinical data of 8 patients with postoperative distal ureteral obstruction after radical cystectomy treated at the First Affiliated Hospital of Nanjing Medical University during Aug.2018 and Jun.2024.The cohort included 7 males and 1 female,aged 51-68 years(mean:58.8 years).Preoperative imaging confirmed the obstruction site and predicted its etiology.All patients underwent robot-assisted Wallace ileal conduit and were regularly followed postoperatively.Perioperative data were statistically analyzed.Results All 8 procedures were successfully completed.The operation time ranged from 120 to 398 minutes(mean:298.38 minutes),and intraoperative blood loss from 50 to 300 mL(mean:112.5 mL).Postoperative complications occurred in 3 cases according to the Clavien-Dindo classification:one Grade Ⅰ and two Grade Ⅱ,with no major postoperative complications(Grade Ⅲ and above)observed.During a follow-up of 21-77 months,hydronephrosis and renal function showed varying degrees of improvement.Conclusion Robot-assisted Wallace ileal conduit is safe,feasible,and effective in the treatment of ureteral obstruction following radical cystectomy.However,for malignant obstruction caused by tumor recurrence,combined comprehensive therapy is necessary to reduce recurrence risk.
4.Clinical efficacy of robot-assisted Wallace ileal conduit in the treatment of ureteral obstruction after radical cystectomy
Tianxiao HONG ; Chaoran ZHAO ; Rongjie BAI ; Pengchao LI
Journal of Modern Urology 2025;30(10):860-864
Objective To investigate the feasibility and efficacy of robot-assisted Wallace ileal conduit in the treatment of ureteral obstruction following radical cystectomy.Methods A retrospective analysis was conducted on the clinical data of 8 patients with postoperative distal ureteral obstruction after radical cystectomy treated at the First Affiliated Hospital of Nanjing Medical University during Aug.2018 and Jun.2024.The cohort included 7 males and 1 female,aged 51-68 years(mean:58.8 years).Preoperative imaging confirmed the obstruction site and predicted its etiology.All patients underwent robot-assisted Wallace ileal conduit and were regularly followed postoperatively.Perioperative data were statistically analyzed.Results All 8 procedures were successfully completed.The operation time ranged from 120 to 398 minutes(mean:298.38 minutes),and intraoperative blood loss from 50 to 300 mL(mean:112.5 mL).Postoperative complications occurred in 3 cases according to the Clavien-Dindo classification:one Grade Ⅰ and two Grade Ⅱ,with no major postoperative complications(Grade Ⅲ and above)observed.During a follow-up of 21-77 months,hydronephrosis and renal function showed varying degrees of improvement.Conclusion Robot-assisted Wallace ileal conduit is safe,feasible,and effective in the treatment of ureteral obstruction following radical cystectomy.However,for malignant obstruction caused by tumor recurrence,combined comprehensive therapy is necessary to reduce recurrence risk.
5.Praeruptorin A inhibits neutrophil inflammation through ferritin and its role in sepsis
Pengchao YU ; Hong ZHENG ; Yifan HU ; Zhouxin YANG ; Zejia YU ; Jinnan XIA ; Haiying HAN ; Dongyang GUO
Chinese Journal of Microbiology and Immunology 2025;45(3):248-255
Objective:To investigate the potential of praeruptorin A (PA) in alleviating inflammatory damage in sepsis through the inhibition of ferritin expression.Methods:C57BL/6 mice were intraperitoneally injected with lipopolysaccharide (LPS) to establish the model of sepsis. After 6 and 12 h of PA intervention, serum levels of inflammatory cytokines IL-6 and TNF-α were measured by ELISA. Kidney tissues were collected at 72 h for HE staining to assess inflammatory cell infiltration and tissue damage. Human neutrophils were divided into four groups: control, LPS, ferritin, and LPS+ ferritin groups. After 12 h of intervention, qRT-PCR was used to detect the expression of IL-6 and TNF-α mRNA. In order to observe the effect of PA on the expression of inflammatory cytokines and ferritin, human neutrophils were grouped into control, LPS, and LPS+ PA (2/3/4 μmol/L) groups. After 12 h of intervention, qRT-PCR was performed to measure the expression of IL-1β, IL-6, TNF-α, and ferritin mRNA; ELISA was used to quantify the levels of IL-1β, IL-6, and TNF-α in culture supernatants; Western blot was used to analyze the expression of ferritin. Molecular docking was conducted to verify interactions between PA and ferritin.Results:Significant inflammatory cell recruitment, tissue damage, and elevated serum levels of IL-6 and TNF-α ( P<0.01) were observed in mice with LPS-induced sepsis. PA significantly inhibited cytokine secretion ( P<0.01) and alleviated tissue injury in sepsis mice. In human neutrophil models, ferritin upregulated the expression of IL-6 and TNF-α mRNA ( P<0.01); LPS stimulation alone increased the expression of IL-1β, IL-6, TNF-α, and ferritin at both mRNA and protein levels ( P<0.01), while co-stimulation with PA (3/4 μmol/L) significantly reversed the aforementioned results ( P<0.01). Molecular docking confirmed there were interaction sites between PA and ferritin. Conclusion:PA inhibits the release of inflammatory cytokines and alleviates tissue damage in sepsis, and the potential mechanism may involve modulating ferritin expression to suppress inflammatory responses.
6.Construction of a prediction model for muscular invasion in upper urinary tract urothelial carcinoma based on preoperative MRI features
Haonan CHEN ; Lingkai CAI ; Hongyuan DING ; Hao JI ; Tianxiao HONG ; Hao YU ; Qikai WU ; Chaoran ZHAO ; Xiao YANG ; Qiang CAO ; Xiancheng ZHAO ; Pengchao LI ; Qiang LYU
Chinese Journal of Urology 2025;46(9):661-668
Objective:To construct a nomogram based on preoperative MRI imaging features for the prediction of muscle-invasive upper urinary tract urothelial carcinoma(UTUC)and evaluate its performance.Methods:This retrospective cohort study analyzed the clinical data of 99 UTUC patients treated at the First Affiliated Hospital of Nanjing Medical University from April 2018 to May 2024. Among them,69(69.7%)were male and 30(30.3%)were female,with a median age of 67.0 years. All patients underwent preoperative MRI and radical nephroureterectomy. According to postoperative pathology,tumors staged ≥ T 2 were assigned to the muscle-invasive group,and those staged ≤ T 1 were assigned to the non-muscle-invasive group. Baseline data,pathological information,and imaging characteristics were collected and compared between the two groups. Logistic regression analysis was performed to identify risk factors for muscle-invasive UTUC,and a nomogram was constructed. The diagnostic performance of the model was assessed using receiver operating characteristic(ROC)curves,calibration curves,and decision curve analysis(DCA). Results:Among the 99 patients,70(70.7%)were diagnosed with muscle-invasive UTUC,and 29(29.3%)with non-muscle-invasive UTUC. The muscle-invasive group had significantly larger tumor size[4.5(2.8,7.0)cm vs. 3.0(2.3,4.5)cm, P = 0.029],a higher incidence of multifocal tumors[37.1%(26/70)vs. 3.5%(1/29), P < 0.001],patchy tumors[30.0%(21/70)vs. 6.9%(2/29), P = 0.019],spiculated tumor margins[52.9%(37/70)vs. 17.2%(5/29), P = 0.001],tumor compression on renal parenchyma or periureteral/peripelvic fat[68.6%(48/70)vs. 10.3%(3/29), P < 0.001],high-grade pathology[92.9%(65/70)vs. 75.9%(22/29), P = 0.043],lymph node metastasis[28.6%(20/70)vs. 0, P = 0.001],and lymphovascular invasion[42.9%(30/70)vs. 10.3%(3/29), P=0.002]. The apparent diffusion coefficient(ADC)values[0.9(0.8,1.1)× 10 -3 mm2/s vs. 1.1(1.0,1.4)× 10 -3 mm2/s, P < 0.001]and normalized ADC(NADC)values[0.8(0.7,1.0)vs. 0.9(0.8,1.1), P = 0.002]were significantly lower in the muscle-invasive group. Univariate logistic regression identified multifocality,patchy tumor patterns,spiculated tumor margins,tumor compression on renal parenchyma or periureteral/peripelvic fat,and low NADC values as risk factors for muscle-invasive UTUC(all P < 0.05). Multivariate analysis revealed multifocality( OR = 17.903,95% CI 1.650 - 194.253, P = 0.018),tumor compression on renal parenchyma or perirenal / ureteral fat( OR = 14.690,95% CI 3.069 - 70.323, P < 0.001),and low NADC value( OR = 0.016,95% CI 0.001 - 0.471, P = 0.017)as independent risk factors. A nomogram was constructed based on these factors. The area under the ROC curve(AUC)of the model was 0.898(95% CI 0.838 - 0.957),with an optimal cutoff value of 0.639. The model showed an accuracy of 83.8%,sensitivity of 81.4%,and specificity of 89.7%. Calibration curves indicated good calibration,and DCA showed that the model provided substantial clinical net benefit. Conclusions:This study constructed a nomogram based on preoperative MRI features,including tumor multifocality,compression on renal parenchyma or periureteral/peripelvic fat and NADC value,which demonstrates good predictive performances for muscle-invasive UTUC.
7.Construction of a prognostic model for intracranial aneurysm rupture with hematoma clipping surgery
Xiaohong GUO ; Junkang FANG ; Zhenyan LU ; Yi WU ; Pengchao HONG ; Xiaokang FANG
China Modern Doctor 2024;62(21):21-25
Objective To explore the influencing factors of poor prognosis after clipping in patients with ruptured intracranial aneurysm and hematoma,and to construct a clinical prediction model.Methods A total of 151 patients with aneurysmal intracranial hematoma in Dongyang People's Hospital were selected from September 2017 to October 2023.3 months after operation,the patients were grouped by modified Rankin scale(mRS),with 93 cases in good prognosis group and 58 cases in poor prognosis group.Univariate analysis and multivariate Logistic regression analysis were used to explore the risk factors affecting the poor prognosis of patients with postoperative prognosis,and a poor prognostic prediction model for patients with intracranial aneurysm rupture and hematoma clamping was constructed,the discriminant validity of the area under the curve(AUC)was evaluated,and the fit of the model was established using the Hosmer-Lemeshow test.Results The Hunt-Hess gradeⅣ-Ⅴ(OR=5.339),modified Fisher grade Ⅲ-Ⅳ(OR=5.145),hematoma volume≥ 50ml(OR=7.426),hematoma clearance rate was≤50%(OR=8.381),size of the responsible aneurysm>5mm(OR=3.053),operation time window>5h(OR=2.659),and intraoperative vascular operation time>3h(OR=2.305)were independent risk factors for poor prognosis after clipping in patients with intracranial aneurysm ruptured and intracranial hematoma(P<0.05).The AUC of the poor prognosis prediction model of patients with intracranial aneurysm rupture with hematoma after clipping was 0.863(95%CI:0.781-0.946,P<0.001),the specificity was 79.6%,the sensitivity was 86.2%,and the prediction accuracy was 82.1%.Hosmer-Lemeshow testx2=5.778,P=0.679,and there was no significant difference between the predicted value of the model and the actual observed value.Conclusion Hunt-Hess grade Ⅳ-Ⅴ,the modified Fisher grade Ⅲ-Ⅳ,hematoma volume≥50ml,hematoma clearance rate≤50%,responsible aneurysm size>5mm,operation time window>5h,and intraoperative vascular operation time>3h were independent risk factors for poor prognosis after clipping in patients with intracranial aneurysm ruptured.The model constructed in this study has high predictive performance and can provide guidance for the treatment and postoperative recovery of patients undergoing craniotomy and clipping surgery in clinical practice.
8.Current study on the podocyte phenotypic transformation of diabetic nephropathy and its medical intervention
Pengchao HOU ; Yuzhi HONG ; Xun YE
China Modern Doctor 2014;(35):157-160
Diabetic nephropathy (DN) is one of the most common and severe complications of diabetic microangiopa-thy which gradually become the major cause of end-stage renal disease (ESRD) in recent years, even though its patho-genesis remains to be elucidated. Proteinuria is one of important malignant factors leading to the deterioration of DN as well as its mainly clinical feature. Lately experimental evidences show that podocyte phenotypic transformation could be a causative role in the genesis of the early DN proteinuria. In this context, it ’s necessary to review the relative bio-logical characteristics of podocyte phenotypic transformation, its associated signaling pathways, its relationship between proteinuria and the possible mechanism of its medical intervention including valsartan and triptolide.

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