177Lu-prostate specific membrane antigen(PSMA)radio-ligand therapy has been approved abroad for advanced prostate cancer and has been in several clinical trials in China.Based on domestic clinical practice and experimental data and referred to international experience and viewpoints,the expert group forms a consensus on the clinical application of 177Lu-PSMA radio-ligand therapy in prostate cancer to guide clinical practice.

Objective To predict the core targets and action pathways of Hedysari Radix based on UPLC-MS/MS and network pharmacology methods,and to verify the results of network pharmacology by molecular docking and molecular dynamics techniques.This article aims to investigate immune regulation mechanism of effective components absorbed into blood from Hedysari Radix.Methods Qualitative quantification of effective components absorbed into blood from Hedysari Radix were operated by using UPLC-MS/MS technique.The corresponding targets of effective components absorbed into blood from Hedysari Radix were screened by TCMSP and HERB databases.Targets of immune-related disease were obtained through DisGeNET,OMIM,TTD,and MalaCards databases.The network of"components absorbed into blood from Hedysari Radix-immune-related diseases"was then constructed.GO and KEGG enrichment analysis and mapped the PPI network were performed.Molecular docking and molecular dynamics techniques were applied for validation.Results A total of 8 prototype components absorbed into blood,synergistically acting on 101 targets,were identified by UPLC-MS/MS.They mediated 538 biological processes including immune response,positive regulation of gene expression,receptor binding,and cytokine activity.Meanuhile,116 signaling pathways,such as HIF-1,Toll-like receptor,JAK-STAT,T cell receptor,PI3K-Akt,and FoxO etc.were involved.The core targets were MAPK14,PTGS2,MMP9,PPARG,CCND1,etc..The results of molecular docking showed that formononetin and calycosin had strong docking binding activity with MAPK14.And molecular dynamics simulations further demonstrated that the binding between MAPK14 and formononetin or calycosin had good structural stability and binding affinity.Conclusion The results of serum pharmacochemistry,network pharmacology and molecular dynamics were verified to reveal the material basis and mechanism of Hedysari Radix in regulating immunity.The aim of this study is to provide scientific basis for its immunomodulatory mechanism.

Objective:To explore the value of the imaging nomogram model based on preoperative CT features of patients with small intestinal stromal tumor (SIST) in predicting pathological risk classification.Methods:This was a cohort study. The patients who were diagnosed as primary SIST by postoperative pathology in Cancer Hospital, Chinese Academy of Medical Sciences from January 2014 to October 2023 were retrospectively included. According to the modified 2008 National Institutes of Health classification criteria, the patients were divided into a pathological intermediate/high-risk group (86 cases) and a very low/low-risk group (56 cases). The features of preoperative enhanced CT images of SIST were analyzed, including tumor boundary, necrosis, intra-tumoral hemorrhage, intra-tumoral calcification, growth pattern, enhancement pattern, enhancement degree, enlarged vessels feeding or draining the mass (EVFDM), and tumor location. Patients were followed up to determine the recurrence-free survival (RFS). Univariate and multivariate logistic regression were used to screen the independent predictors of SIST with pathological medium/high-risk group. The independent predictors were combined to construct an imaging prediction model, and a nomogram was drawn. The receiver operating characteristic curve was used to evaluate the predictive efficacy of the model. The Kaplan-Meier method was used to draw the survival curve, and the log-rank test was used to compare the differences in RFS.Results:Univariate logistic regression results showed that tumor shape, necrosis, intra-tumoral hemorrhage, EVFDM, and tumor location were potentially related to medium/high-risk SIST. Multivariate logistic regression results showed that tumor shape ( OR=3.92, 95% CI 1.58-9.71, P=0.003), necrosis ( OR=4.60, 95% CI 1.91-11.09, P<0.001), and EVFDM ( OR=6.25,95% CI 1.74-22.47, P=0.005) were independent predictors of pathological intermediate/high-risk SIST. The area under the curve of the imaging predictive model combining the three predictors to predict the intermediate/high-risk SIST was 0.835 (95% CI 0.769-0.901), the sensitivity was 0.810, the specificity was 0.839, and the accuracy was 0.789. Taking the cut-off value (0.810) as the boundary value, the patients were divided into the high-risk group (74 cases) and the low-risk group (68 cases) according to the prediction results. The median RFS of the predicted high-risk group was poorer than that of the predicted low-risk group, and the difference was statistically significant ( χ2=5.20, P=0.023). Conclusions:The imaging nomogram model based on preoperative CT image features shape, necrosis, and EVFDM can effectively predict the pathological intermediate/high-risk SIST before surgery and has important predictive value for postoperative recurrence.

Dysregulation of microRNAs (miRNAs) is involved in abnormal development and pathophysiology in the brain. Although miR-20b plays essential roles in various human diseases, its function in cerebral ischemic stroke remains unclear. A cell model of oxygen glucose deprivation/reoxygenation (OGD/R) and A rat model of middle cerebral artery occlusion/reperfusion (MCAO/R) were constructed. qRT-PCR and western blot were used to evaluate the expression of miR-20b and TXNIP. Cell viability was detected by MTT assay, and cell apoptosis was evaluated by flow cytometry. Targetscan and Starbase were used to predict the potential targets of miR-20b. Luciferase reporter assay was applied to determine the interaction between miR-20b and TXNIP. Rescue experiments were conducted to confirm the functions of miR-20b/TXNIP axis in cerebral ischemic stroke. MiR-20b was significantly downregulated after I/R both in vitro and in vivo. Upregulation of miR-20b inhibited OGD/R-induced neurons apoptosis and attenuated ischemic brain injury in rat model. Bioinformatic prediction suggested that TXNIP might be a target of miR-20b, and luciferase reporter assay revealed that miR-20b negatively regulated TXNIP expression by directly binding to the 3’-UTR of TXNIP. Downregulation of TXNIP inhibited OGD/R-induced neurons apoptosis in vitro and ischemic brain injury in vivo. Rescue experiments indicated that downregulation of TXNIP effectively reversed the effect of miR-20b inhibitor in neurons apoptosis after OGD/R-treatment and ischemic brain injury in a mouse model after MCAO/R-treatment. Our study demonstrated that upregulation of miR-20b protected the brain from ischemic brain injury by targeting TXNIP, extending our understanding of miRNAs in cerebral ischemic stroke.

Dysregulation of microRNAs (miRNAs) is involved in abnormal development and pathophysiology in the brain. Although miR-20b plays essential roles in various human diseases, its function in cerebral ischemic stroke remains unclear. A cell model of oxygen glucose deprivation/reoxygenation (OGD/R) and A rat model of middle cerebral artery occlusion/reperfusion (MCAO/R) were constructed. qRT-PCR and western blot were used to evaluate the expression of miR-20b and TXNIP. Cell viability was detected by MTT assay, and cell apoptosis was evaluated by flow cytometry. Targetscan and Starbase were used to predict the potential targets of miR-20b. Luciferase reporter assay was applied to determine the interaction between miR-20b and TXNIP. Rescue experiments were conducted to confirm the functions of miR-20b/TXNIP axis in cerebral ischemic stroke. MiR-20b was significantly downregulated after I/R both in vitro and in vivo. Upregulation of miR-20b inhibited OGD/R-induced neurons apoptosis and attenuated ischemic brain injury in rat model. Bioinformatic prediction suggested that TXNIP might be a target of miR-20b, and luciferase reporter assay revealed that miR-20b negatively regulated TXNIP expression by directly binding to the 3’-UTR of TXNIP. Downregulation of TXNIP inhibited OGD/R-induced neurons apoptosis in vitro and ischemic brain injury in vivo. Rescue experiments indicated that downregulation of TXNIP effectively reversed the effect of miR-20b inhibitor in neurons apoptosis after OGD/R-treatment and ischemic brain injury in a mouse model after MCAO/R-treatment. Our study demonstrated that upregulation of miR-20b protected the brain from ischemic brain injury by targeting TXNIP, extending our understanding of miRNAs in cerebral ischemic stroke.

Objective:To investigate the combined value of gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA) enhanced magnetic resonance imaging (MRI) and diffusion-weighted imaging (DWI) in predicting pathological microvascular invasion (pMVI) preoperatively, and to determine the relationship between prediction results and prognosis in hepatocellular carcinoma (HCC) patients.Methods:A total of 181 newly diagnosed HCC patients were enrolled in this study. Imaging characteristics and the apparent diffusion coefficient (ADC) value of DWI were analyzed. The differences of imaging characteristics and ADC values between different pMVI groups were analyzed.Multivariate logistic regression and receiver operating characteristic (ROC) curve were used to analyze the value for pMVI prediction by using significant parameters. The patients were grouped based on MRI predicted MVI (mrMVI), and the relationship between mrMVI and recurrence free survival time (RFS) was analyzed.Results:Fifty-one patients were pMVI positive and 130 patients were pMVI negative. The ADC value in pMVI positive group were (1.10±0.17)×10 -3 mm 2/s, significantly lower than (1.27±0.22)×10 -3 mm 2/s of pEMVI negative group ( P<0.001). The incidence rates of incomplete enhancing "capsule" , non-smooth tumor margin, arterial peritumoral enhancement, mosaic architecture and peritumoral hypointensity on hepatobiliary phase (HBP) in pMVI positive group were significantly higher than those of negative group (all P<0.05). Multivariate logistic regression analysis showed that tumor margin, arterial peritumoral enhancement, peritumoral hypointensity on HBP and ADC value were independently associated with pMVI. ROC analysis showed that the area under curve, sensitivity and specificity of pMVI predicted by combined parameters were 0.830, 76.5% and 81.5%, respectively. The median RFS of mrMVI positive group was 23.6 months, significantly lower than 38.2 months of mrEMVI negative group ( P=0.004). Conclusion:Tumor margin, arterial peritumoral enhancement, peritumoral hypointensity on HBP and ADC value are independent predictors of pMVI in HCC, and mrMVI is related with RFS.

Objective:To assess the optimal cut-off value between early recurrence and late recurrence of patients with hepatocellular carcinoma (HCC) after radiofrequency ablation (RFA), and to construct a nomogram to predict early recurrence.Methods:A total of 119 patients with HCC who recurred after RFA in Cancer Hospital, Chinese Academy of Medical Sciences from January 2012 to December 2017 were identified. The optimal cut-off value to distinguish early and late recurrence was determined based on differences in post recurrence survival (PRS) by minimum P-value approach. The clinical and radiographic risk factors for early recurrence were identified by univariate and multivariate Logistic regression analysis. The predictive nomogram was constructed by these factors and internally validated. Results:The optimal cut-off value to distinguish early recurrence and late recurrence was 12 months after RFA ( P=0.005). The patients were divided into early recurrence group (47 cases) and late recurrence group (72 cases). The lower quartile PRS (Q1-PRS) and lower quartile overall survival (Q1-OS) were 11.1 and 19.1 months in the early recurrence group, which were shorter than 31.6 and 81.0 months in the late recurrence group ( P=0.005 and P<0.001, respectively). The independent risk factors of early recurrence were alpha fetoprotein (AFP) ( OR=8.459, 95% CI: 2.231-32.073), albumin(ALB) ( OR=0.251, 95% CI: 0.047-1.339), number of lesions ( OR=3.842, 95% CI: 1.424-10.365) and peritumoral enhancement ( OR=8.05, 95% CI: 1.23-52.80), which were further incorporated into constructing the predictive nomogram of early recurrence of HCC after RFA. Internal validation results showed the area under the curve, sensitivity, specificity of the receiver operating characteristic (ROC) curve were 0.839, 68.1% and 93.1%, respectively. The calibration curve showed the predicted curve of nomogram was close to the ideal curve. Hosmer-Lemeshow test showed there was no significant difference between the predicted results of nomogram and the actual results ( P=0.424). Conclusions:An interval of 12 months after RFA is the optimal cut-off value for defining early recurrence and late recurrence. The nomogram is integrated by clinical and radiographic features, which can potentially predict early recurrence of HCC after RFA and may offer useful guidance for individual treatment or follow up.

Objective:To investigate the combined value of gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA) enhanced magnetic resonance imaging (MRI) and diffusion-weighted imaging (DWI) in predicting pathological microvascular invasion (pMVI) preoperatively, and to determine the relationship between prediction results and prognosis in hepatocellular carcinoma (HCC) patients.Methods:A total of 181 newly diagnosed HCC patients were enrolled in this study. Imaging characteristics and the apparent diffusion coefficient (ADC) value of DWI were analyzed. The differences of imaging characteristics and ADC values between different pMVI groups were analyzed.Multivariate logistic regression and receiver operating characteristic (ROC) curve were used to analyze the value for pMVI prediction by using significant parameters. The patients were grouped based on MRI predicted MVI (mrMVI), and the relationship between mrMVI and recurrence free survival time (RFS) was analyzed.Results:Fifty-one patients were pMVI positive and 130 patients were pMVI negative. The ADC value in pMVI positive group were (1.10±0.17)×10 -3 mm 2/s, significantly lower than (1.27±0.22)×10 -3 mm 2/s of pEMVI negative group ( P<0.001). The incidence rates of incomplete enhancing "capsule" , non-smooth tumor margin, arterial peritumoral enhancement, mosaic architecture and peritumoral hypointensity on hepatobiliary phase (HBP) in pMVI positive group were significantly higher than those of negative group (all P<0.05). Multivariate logistic regression analysis showed that tumor margin, arterial peritumoral enhancement, peritumoral hypointensity on HBP and ADC value were independently associated with pMVI. ROC analysis showed that the area under curve, sensitivity and specificity of pMVI predicted by combined parameters were 0.830, 76.5% and 81.5%, respectively. The median RFS of mrMVI positive group was 23.6 months, significantly lower than 38.2 months of mrEMVI negative group ( P=0.004). Conclusion:Tumor margin, arterial peritumoral enhancement, peritumoral hypointensity on HBP and ADC value are independent predictors of pMVI in HCC, and mrMVI is related with RFS.

Objective:To assess the optimal cut-off value between early recurrence and late recurrence of patients with hepatocellular carcinoma (HCC) after radiofrequency ablation (RFA), and to construct a nomogram to predict early recurrence.Methods:A total of 119 patients with HCC who recurred after RFA in Cancer Hospital, Chinese Academy of Medical Sciences from January 2012 to December 2017 were identified. The optimal cut-off value to distinguish early and late recurrence was determined based on differences in post recurrence survival (PRS) by minimum P-value approach. The clinical and radiographic risk factors for early recurrence were identified by univariate and multivariate Logistic regression analysis. The predictive nomogram was constructed by these factors and internally validated. Results:The optimal cut-off value to distinguish early recurrence and late recurrence was 12 months after RFA ( P=0.005). The patients were divided into early recurrence group (47 cases) and late recurrence group (72 cases). The lower quartile PRS (Q1-PRS) and lower quartile overall survival (Q1-OS) were 11.1 and 19.1 months in the early recurrence group, which were shorter than 31.6 and 81.0 months in the late recurrence group ( P=0.005 and P<0.001, respectively). The independent risk factors of early recurrence were alpha fetoprotein (AFP) ( OR=8.459, 95% CI: 2.231-32.073), albumin(ALB) ( OR=0.251, 95% CI: 0.047-1.339), number of lesions ( OR=3.842, 95% CI: 1.424-10.365) and peritumoral enhancement ( OR=8.05, 95% CI: 1.23-52.80), which were further incorporated into constructing the predictive nomogram of early recurrence of HCC after RFA. Internal validation results showed the area under the curve, sensitivity, specificity of the receiver operating characteristic (ROC) curve were 0.839, 68.1% and 93.1%, respectively. The calibration curve showed the predicted curve of nomogram was close to the ideal curve. Hosmer-Lemeshow test showed there was no significant difference between the predicted results of nomogram and the actual results ( P=0.424). Conclusions:An interval of 12 months after RFA is the optimal cut-off value for defining early recurrence and late recurrence. The nomogram is integrated by clinical and radiographic features, which can potentially predict early recurrence of HCC after RFA and may offer useful guidance for individual treatment or follow up.

Objective: To evaluate the value of T2WI signal intensity related parameters that can be obtained by magnetic resonance imaging (MRI) for predicting pathological complete response (pCR) after neoadjuvant chemoradiotherapy (nCRT) in patients with locally advanved rectal cancer (LARC). Methods: Signal Intensity of Tumor (SIT) and Signal Intensity of Tumor/Muscle (SIT/M) of MR T2WI before and after neoadjuvant chemoradiotherapy of 101 patients with locally advanced rectal cancer were evaluated by two experienced readers independently. Signal Intensity of Tumor Reduction Rate (SITRR) and Signal Intensity of Tumor/Muscle Reduction Rate (SIT/MRR) were calculated. The difference of related parameters of T2WI tumor signal intensity between the pCR and the non-pCR group were analyzed. Receiver operating characteristic (ROC) analysis was used to assess the diagnostic performance for predicting pCR. Results: Of the 101 patients, 18 were in pCR group and 83 were in non-pCR group. In all patients, the SITpre, SITpost, SITRR, SIT/Mpre, SIT/Mpost and SIT/MRR measured by reader 1 were 197.0 (133.0), 144.2 (69.7), 0.4% (0.5%), 2.6 (0.6), 3.0 (2.3) and 0.4 (0.2)% in pCR group, and 227.0 (99.0), 205 (95.4), 0.1% (0.6%), 2.6 (0.6), 2.6 (1) in non-pCR group, respectively. SITpre, SITpost, SITRR, SIT/Mpre, SIT/Mpost and SIT/MRR measured by reader 2 were 193.0 (135.0), 143.0 (69.8), 0.4% (0.2%), 2.6 (0.6), 1.5 (0.5) and 0.39% (0.2%) in pCR group, and 234.0(108.0), 203(96.5), 0.1% (0.3%), 2.6 (0.6%), 1.7 (0.7) and 0.25% (0.2%) in non-pCR group, respectively. Between the pCR and non-pCR group, there were significant differences in SITpost, SIT/Mpost and SIT/MRR measured by both readers (all P<0.01), but there was no significant differences in SITpre and SIT/Mpre (P>0.05). The difference of SITRR measured by reader 1 was not statistically significant (P=0.415), while the difference of SITRR measured by reader 2 was statistically significant (P=0.001). In patients with rectal non-mucinous adenocarcinoma, SITpost, SIT/Mpost, SITRR and SIT/MRR measured by two physicians were still statistically significant between the pCR and non-pCR group (all P<0.01), but SITpre and SIT/Mpre had no significant difference (P>0.05). ROC curve analysis showed that in all patients, the area under curve (AUC) of SITpost, SIT/Mpost and SIT/MRR for predicting pCR to neoadjuvant chemoradiotherapy in locally advanced rectal cancer was 0.694-0.762, the sensitivity was 68.2%-77.3%, and the specificity was 63.6%-77.3%. In rectal non-mucinous adenocarcinoma patients, the AUC, sensitivity and specificity was 0.704-0.764, 62.7%-78.9% and 66.2%-84.2%, respectively. Conclusions T2WI signal intensity related parameters are potential predictors for pCR in locally advanced rectal cancer after neoadjuvant chemoradiptherapy. The predictive value is higher in non-mucinous adenocarcinoma.