1.Effect of Bushen Huoxue Granule (补肾活血颗粒) on Dopamine Homeostasis and ERK/CREB/VMAT2 Signaling Pathways in the Striatum in Parkinson's Disease Model Mice
Hehao SUN ; Yingfan CHEN ; Peng WANG ; Xiaohan GENG ; Yuzhi ZHANG ; Qian ZHANG ; Min LI ; Shaodan LI ; Minghui YANG
Journal of Traditional Chinese Medicine 2025;66(23):2484-2493
ObjectiveTo investigate the possible mechanism of Bushen Huoxue Granule (补肾活血颗粒, BHG) in treating Parkinson's disease (PD) from the perspecitve of dopamine (DA) homeostasis. MethodsSeventy-two mice were randomly divided into blank group, model group, madopar group and BHG low-, medium- and high-dose groups, with 12 mice in each group. Except for the blank group, all mice were administered intraperitoneal injections of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) for 7 consecutive days to induce a PD model. On the day following the injection, BHG low-, medium- and high-dose groups were administered BHG at doses of 1.25, 2.5, and 5.0 mg/(g·d) by oral gavage, respectively, while the madopar group received madopar tablets at dose of 0.093 8 mg/(g·d) by oral gavage. The blank group and the model group were given 0.2 ml/10 g of distilled water by gavage. All treatments were given once daily for 14 days. Open field test, pole climbing test and grip test were used to evaluate the behavior of mice in each group. Immunohistochemistry was used to detect the expression of tyrosine hydroxylase (TH) in striatum. Nissl staining was used to detect the activity of striatal neurons. The contents of DA and 3,4-dihydroxyphenylacetic acid (DOPAC) in striatum were detected by ultra performance liquid chromatography tandem mass spectrometry. The number and volume of synaptic vesicles were observed by transmission electron microscope. The expression of vesicular monoamine transporter 2 (VMAT2) in striatum was detected by immunofluorescence. Western Blot was used to detect the expression of extracellular signal-regulated kinase (ERK), phosphorylated ERK (p-ERK), cAMP response element-binding protein (CREB), phosphorylated CREB (p-CREB) and VMAT2 in striatum. ResultsCompared to the blank group, mice in the model group showed a significant decline in total distance and average speed in the open field test, along with an increase in total resting time; in the pole test, both the time required for the mice to turn completely downward (T-turn) and the total time taken to reach the bottom of the pole (T-total) were prolonged; forelimb grip strength was reduced; in the striatum, the mean optical density of TH, the average fluorescence intensity of VMAT2 protein, and DA content all decreased, while the number of striatal neurons was reduced, and the DOPAC/DA ratio was elevated; the levels of p-ERK/ERK, p-CREB/CREB, and VMAT2 in the striatum significantly decreased (P<0.01); transmission electron microscopy revealed that both the number and volume of synaptic vesicles in striatal neurons were markedly reduced. Compared to the model group, mice in the madopar group and BHG low-, medium- and high-dose groups showed significant improvements in all the above indicators (P<0.05 or P<0.01). Compared to madopar group, the BHG high-dose group exhibited increased DA content and elevated p-CREB/CREB ratio in the striatum (P<0.05). Compared to the BHG low-dose group, the BHG high-dose group showed increased total distance and mean velocity, decreased total resting time, T-turn, and T-total, as well as enhanced forelimb grip strength; moreover, the average fluorescence intensity of VMAT2 protein, DA content, p-ERK/ERK, p-CREB/CREB, and VMAT2 levels in the striatum were all significantly elevated (P<0.05 or P<0.01). ConclusionBHG may restore DA homeostasis and alleviate the damage of dopaminergic neurons by regulating ERK/CREB/VMAT2 signaling pathway.
2.Predictive value of a combined model for lymph node metastasis in NSCLC based on primary lesion radiomics from 18F-FDG PET/CT
Ruihe LAI ; Yue TENG ; Jian RONG ; Dandan SHENG ; Yuzhi GENG ; Jianxin CHEN ; Chong JIANG ; Chongyang DING ; Zhengyang ZHOU
Journal of International Oncology 2025;52(3):144-151
Objective:To evaluate the value of a combined model based on primary lesion 18F-fluorodeoxyglucose ( 18F-FDG) PET/CT radiomics for predicting lymph node metastasis in non-small cell lung cancer (NSCLC) . Methods:A retrospective analysis was conducted on the clinical data of 203 NSCLC patients who underwent pre-treatment PET/CT imaging at Nanjing Drum Tower Hospital from June 2013 to July 2023. Patients were randomly assigned to the training set ( n=142) and the validation set ( n=61) at a ratio of 7∶3. A predictive model was developed in the training set, and its predictive performance and clinical application value were assessed in both the training and validation sets. Traditional PET/CT parameters and PET/CT radiomics features of the primary lesion were obtained by 3D-slicer software. Least absolute shrinkage and selection operator (LASSO), random forest, and extreme gradient boosting were performed to extract features. Support vector machine was used to construct a radiomics score (Radscore). Univariate and multivariate logistic regression analysis was used to predict the influencing factors of lymph node metastasis in NSCLC patients and to establish models. Predictive performance of the models was evaluated by receiver operator characteristic (ROC) curves and clinical application value was assessed by calibration curves and decision curve analysis (DCA) . Results:Among 203 NSCLC patients, 116 had lymph node metastasis, with 64 cases in the training set and 52 cases in the validation set. Three complementary classical machine learning methods were used for feature screening, and finally 10 radiomics features were obtained. The optimal threshold for Radscore-PET was 0.43 and the optimal threshold for Radscore-CT was 0.39. Univariate analysis showed that, sex ( OR=0.48, 95% CI: 0.24-0.95, P=0.036), tumor marker levels ( OR=3.81, 95% CI: 1.84-7.91, P<0.001), long diameter of tumor ( OR=2.56, 95% CI: 1.27-5.16, P=0.009), short diameter of tumor ( OR=3.73, 95% CI: 1.75-7.92, P=0.001), vacuolar sign ( OR=0.32, 95% CI: 0.12-0.86, P=0.024), ring-like metabolism ( OR=3.67, 95% CI: 1.33-10.13, P=0.012), maximum standardized uptake value (SUV max) ( OR=6.57, 95% CI: 3.03-14.25, P<0.001), metabolic tumor volume (MTV) ( OR=2.91, 95% CI: 1.43-5.92, P=0.003), total lesion glycolysis (TLG) ( OR=4.23, 95% CI: 2.08-8.59, P<0.001), Radscore-PET ( OR=21.93, 95% CI: 9.04-53.20, P<0.001) and Radscore-CT ( OR=13.72, 95% CI: 6.12-30.76, P<0.001) were all influencing factors for predicting lymph node metastasis in NSCLC patients. Multivariate analysis showed that, tumor marker levels ( OR=2.55, 95% CI: 1.11-5.90, P=0.028), vacuolar sign ( OR=0.26, 95% CI: 0.08-0.83, P=0.023), SUV max ( OR=5.94, 95% CI: 1.99-17.75, P=0.001), Radscore-PET ( OR=25.51, 95% CI: 5.92-110.22, P<0.001), and Radscore-CT ( OR=8.68, 95% CI: 2.73-27.61, P<0.001) were independent influencing factors for predicting lymph node metastasis in patients with NSCLC. Based on the above independent influencing factors, models were constructed: the traditional model (tumor marker levels, vacuolar sign, SUV max), the PET model (SUV max, Radscore-PET), the CT model (vacuolar sign, Radscore-CT), and the combined model (tumor marker levels, vacuolar sign, SUV max, Radscore-PET, Radscore-CT). ROC curve analysis showed that, the area under curve (AUC) of the traditional, PET, CT, and combined models in the training set were 0.75 (95% CI: 0.67-0.82), 0.90 (95% CI: 0.84-0.95), 0.85 (95% CI: 0.78-0.90), and 0.94 (95% CI: 0.88-0.97), respectively. The predictive value of the combined model was higher than that of the traditional model ( Z=5.01, P<0.001), the PET model ( Z=1.99, P=0.047), and the CT model ( Z=3.25, P=0.001). In the validation set, the AUCs for the traditional model, PET model, CT model, and combined model were 0.65 (95% CI: 0.52-0.77), 0.86 (95% CI: 0.74-0.93), 0.85 (95% CI: 0.73-0.93), and 0.90 (95% CI: 0.80-0.96), respectively. The predictive value of the combined model was superior to that of the traditional model ( Z=3.23, P=0.001). The sensitivity and specificity of the combined model in the training set were 84.37% and 91.03%, while in the validation set, the sensitivity and specificity were 82.61% and 94.74%, respectively. Calibration curves showed a good agreement between the predicted and actual probabilities in both the training and validation sets. DCA showed that the combined models had good discriminative ability in both the training and validation sets. Conclusions:Tumor marker levels, vacuolar sign, SUV max, Radscore-PET, and Radscore-CT are all independent influencing factors for predicting lymph node metastasis in patients with NSCLC. The combined model based on these factors demonstrates excellent predictive performance and clinical application value for predicting lymph node metastasis in NSCLC.
3.Prognostic value of 18F-FDG PET/CT metabolic parameters in small cell lung cancer
Ruihe LAI ; Dandan SHENG ; Jian HE ; Chongyang DING ; Yuzhi GENG
Journal of International Oncology 2025;52(10):614-620
Objective:To evaluate the prognostic value of 18F-fluorodeoxyglucose ( 18F-FDG) PET/CT metabolic parameters in small cell lung cancer (SCLC) . Methods:A retrospective analysis was conducted on the clinical and imaging data of 156 SCLC patients, who underwent 18F-FDG PET/CT imaging and were diagnosed by histopathological examination at Nanjing Drum Tower Hospital, Affiliated Hospital of Nanjing University Medical School from September 2013 to February 2024. The metabolic tumor volume (MTV), total lesion glycolysis (TLG), linear regression slope, area under the curve of cumulative standard uptake value (SUV) volume histogram (AUC-CSH), and coefficient of variation (CV) were calculated using LIFEx software with different SUV thresholds. Univariate and multivariate analyses were performed using Cox proportional hazards model. Patient stratification was based on the critical values determined by receiver operator characteristic (ROC) curve analysis. The survival curve was plotted using the Kaplan-Meier method and log-rank test was performed. Results:Univariate analysis showed that MTV 40% ( HR=2.91, 95% CI: 1.55-5.47, P=0.001), MTV 60% ( HR=2.31, 95% CI: 1.29-4.17, P=0.005), TLG 40% ( HR=2.07, 95% CI: 1.19-3.60, P=0.010), linear regression slope ( HR=0.45, 95% CI: 0.26-0.79, P=0.005), and CV 40% ( HR=0.27, 95% CI: 0.08-0.84, P=0.024) were factors affecting progression-free survival (PFS) in SCLC patients. MTV 40% ( HR=1.98, 95% CI: 1.22-3.22, P=0.005), MTV 60% ( HR=1.80, 95% CI: 1.12-2.88, P=0.015), MTV 80% ( HR=1.71, 95% CI: 1.08-2.74, P=0.024), TLG 40% ( HR=3.68, 95% CI: 1.59-8.49, P=0.002), linear regression slope ( HR=0.49, 95% CI: 0.30-0.80, P=0.004), and AUC-CSH 80% ( HR=0.44, 95% CI: 0.23-0.84, P=0.013) were found to be factors affecting overall survival (OS) in SCLC patients. Multivariate analysis revealed that MTV 40% ( HR=4.76, 95% CI: 1.11-20.50, P=0.036) was an independent factor influencing PFS, and TLG 40% ( HR=3.19, 95% CI: 1.02-9.92, P=0.046) was an independent factor influencing OS in SCLC patients. ROC curve analysis identified the optimal cutoff value for MTV 40% in predicting PFS as 5.5cm 3 and the optimal cutoff value for TLG 40% in predicting OS as 41.5 g in SCLC patients. Survival analysis showed that patients with MTV 40%≤5.5 cm 3 ( n=33) had a median PFS that was not reached, while patients with MTV 40%>5.5 cm 3 ( n=123) had a median PFS of 10.3 months, with a statistically significant difference ( χ2=12.09, P=0.001). For patients with TLG 40%≤41.5 g ( n=35), the median OS was not reached, whereas for TLG 40%>41.5 g ( n=121), the median OS was 31.6 months, with a statistically significant difference ( χ2=10.55, P=0.001) . Conclusions:The 18F-FDG PET/CT metabolic parameter MTV 40% is an independent factor influencing PFS, while TLG 40% is an independent factor influencing OS in SCLC patients. The above two parameters may serve as indicators for assessing the prognosis of SCLC patients.
4.Stage-by-stage clinical outcomes of percutaneous nephrolithotomy for calculous pyonephrosis:a Meta-analysis
Bin YANG ; Erkang GENG ; Chuanping WAN ; Yuanjian NIU ; Yuzhi LI ; Jianhe LIU
Journal of Modern Urology 2024;29(1):29-36
【Objective】 To identify the best surgical treatment for patients with calculous pyonephrosis by evaluating the clinical effectiveness of percutaneous nephrolithotripsy (PCNL) in stageⅠ, percutaneous nephrostomy (PCN) in stageⅠ, and percutaneous nephrolithotripsy in stageⅡ. 【Methods】 For publications published between Jan.2012 and Oct.2022, we thoroughly examined the databases of PubMed, Cochrane Library, Web of Science, EMBASE, CNKI, Wanfang, and VIP.We then chosed the literature based on the inclusion and exclusion criteria.After data were retrieved and literature quality was assessed, Review Manager software (RevMan 5.4.3, Cochrane Collaboration, Oxford, UK) was utilized to Meta-analysis. 【Results】 Out of 688 participants across 105 researches, we chosed 11 trials.Among them, 341 patients received both stageⅠPCN and stage ⅡPCNL (hereinafter referred to as phase ⅡPCNL), while 347 patients received stageⅠPCNL.According to the results of the Meta-analysis, there was no discernible difference between stage Ⅰ PCNL and stage Ⅱ PCNL in terms of stone clearance rate (P=0.95), operation duration (P=0.48), postoperative septic shock (P=0.36), or perirenal effusion infection (P=0.27).There were significant differences between stage Ⅰ PCNL and stage Ⅱ PCNL in fever (P=0.03), indwelling nephrostomy tube time (P=0.01), hospitalization costs (P=0.01), hospitalization time (P=0.01), and postoperative hospitalization time (P=0.02).The following two regimens were comparable in terms of stone clearance rate, operating time, postoperative perirenal effusion infection, and septic shock for patients with calculous pyonephrosis.Despite the fact that there were more patients who developed fever after stage ⅠPCNL, hospitalization costs were lower, indwelling nephrostomy tube time, overall hospitalization time, and postoperative hospitalization time were all reduced. 【Conclusion】 ⅠPCNL was affordable, safe, and successful for treating renal and upper ureteral calculi with pyonephrosis, and it had some promotional value in clinical practice.

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