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.

Background::Ainuovirine (ANV) is a new generation of non-nucleoside reverse transcriptase inhibitor for the treatment of human immunodeficiency virus (HIV) type 1 infection. This study aimed to evaluate the population pharmacokinetic (PopPK) profile and exposure-response relationship of ANV among people living with HIV.Methods::Plasma concentration-time data from phase 1 and phase 3 clinical trials of ANV were pooled for developing the PopPK model. Exposure estimates obtained from the final model were used in exposure-response analysis for virologic responses and safety responses.Results::ANV exhibited a nonlinear pharmacokinetic profile, which was best described by a two-compartment model with first-order elimination. There were no significant covariates correlated to the pharmacokinetic parameters of ANV. The PopPK parameter estimate (relative standard error [%]) for clearance adjusted for bioavailability (CL/F) was 6.46 (15.00) L/h, and the clearance of ANV increased after multiple doses. The exposure-response model revealed no significant correlation between the virologic response (HIV-RNA <50 copies/mL) at 48 weeks and the exposure, but the incidence of adverse events increased with the increasing exposure ( P value of steady-state trough concentration and area under the steady-state curve were 0.0177 and 0.0141, respectively). Conclusions::Our PopPK model supported ANV 150 mg once daily as the recommended dose for people living with HIV, requiring no dose adjustment for the studied factors. Optimization of ANV dose may be warranted in clinical practice due to an increasing trend in adverse reactions with increasing exposure.Trial registration::Chinese Clinical Trial Registry https://www.chictr.org.cn (Nos. ChiCTR1800018022 and ChiCTR1800019041).

Objective:To investigate the feasibility and efficacy of three mini-incision double eyelid blepharoplasty with concurrent reposition of orbital fat pad to correct sunken upper eyelids.Methods:The data of patients who underwent orbital fat reposition to correct upper eyelid depression during the period from January 2018 to April 2021 in the Medical Plastic and Cosmetic Center of Beijing Tongren Hospital affiliated to Capital Medical University were retrospectively analyzed. During the operation, the central mass of orbital fat and its lateral extension were fully dissociated, and then transferred and fixed inward through three mini-incisions. Postoperative follow-up was performed to observe the improvement of the double eyelid shape and upper eyelid depression, and the patient satisfaction was recorded.Results:A total of 72 patients (140 eyes) were included in this study, including 1 male and 71 females, with an average age of 28 years (19-40 years old), 122 eyes with mild upper eyelid depression and 18 eyes with moderate upper eyelid depression before operation. Postoperative follow-up was 6-24 months, with an average of 11 months. The curvature of the double eyelid after operation was smooth and basically symmetrical. Among the 122 eyes with mild upper eyelid depression before operation, 118 eyes were completely corrected after operation, and 4 eyes were not improved. Of the 18 eyes, 3 eyes were completely corrected after operation, and 15 eyes still had mild upper lid depression. The overall satisfaction rate was 93.1% (67/72), the rate of double eyelid failure was 3.6% (5/140), and no other serious complications were found.Conclusions:Three mini-incision double eyelid blepharoplasty simultaneously with orbital fat reposition can effectively correct mild and moderate sunken upper eyelid deformity. The postoperative double eyelid shape is stable with high satisfaction rate.

Objective:To explore the value of MRI features in predicting the pathological grade of rectal neuroendocrine tumors and to develop a predicting model.Methods:A retrospective analysis was performed on 30 cases of rectal neuroendocrine tumors confirmed by surgery and pathology between 2013 and 2019. All of them underwent plain rectal MRI, DWI and dynamic contrast-enhanced MRI. The clinical features and MRI characteristics (ie. tumor location, maximum tumor diameter, boundary, growth pattern, enhancement of three-staged lesions, and the lymph node metastasis) were analyzed by statistical methods to evaluate the difference between different tumor pathologic grades (G1, G2 and G3). Characteristics with statistical significance were analyzed by collinearity diagnostics, and stepwise regression method was used to select independent predictors. Ordinal logistic regression analysis was then conducted to develop the predicting model.Results:Maximum tumor diameter, tumor boundary, growth pattern, mr-T, mr-N, EMVI, MRF, T2WI signal intensity, tumor enhancement degree in venous phase and distant metastasis were closely correlated with the pathological grade of rectal neuroendocrine tumors ( P<0.001, 0.001, 0.001, <0.001, 0.001, 0.004, 0.024, 0.015, 0.001, and <0.001, respectively). The mr-T and tumor enhancement degree in venous phase were identified as the independent predictors to construct the prediction model. The model got ideal performance in predicting the grades, with the areas under the receiver operating characteristic (ROC) curves (AUCs) of 0.945, 0.624 and 0.896, the sensitivities were 75.0%, 85.7%, and 90.9% and corresponding specificities were 88.9%, 52.6% and 93.3% for G1, G2 and G3 rectal neuroendocrine tumors, respectively. Conclusion:The model based on mr-T and tumor enhancement degree in venous phase can serve as a clinical tool for predicting the pathological grade of rectal neuroendocrine tumors.

Objective:To investigate the feasibility and efficacy of three mini-incision double eyelid blepharoplasty with concurrent reposition of orbital fat pad to correct sunken upper eyelids.Methods:The data of patients who underwent orbital fat reposition to correct upper eyelid depression during the period from January 2018 to April 2021 in the Medical Plastic and Cosmetic Center of Beijing Tongren Hospital affiliated to Capital Medical University were retrospectively analyzed. During the operation, the central mass of orbital fat and its lateral extension were fully dissociated, and then transferred and fixed inward through three mini-incisions. Postoperative follow-up was performed to observe the improvement of the double eyelid shape and upper eyelid depression, and the patient satisfaction was recorded.Results:A total of 72 patients (140 eyes) were included in this study, including 1 male and 71 females, with an average age of 28 years (19-40 years old), 122 eyes with mild upper eyelid depression and 18 eyes with moderate upper eyelid depression before operation. Postoperative follow-up was 6-24 months, with an average of 11 months. The curvature of the double eyelid after operation was smooth and basically symmetrical. Among the 122 eyes with mild upper eyelid depression before operation, 118 eyes were completely corrected after operation, and 4 eyes were not improved. Of the 18 eyes, 3 eyes were completely corrected after operation, and 15 eyes still had mild upper lid depression. The overall satisfaction rate was 93.1% (67/72), the rate of double eyelid failure was 3.6% (5/140), and no other serious complications were found.Conclusions:Three mini-incision double eyelid blepharoplasty simultaneously with orbital fat reposition can effectively correct mild and moderate sunken upper eyelid deformity. The postoperative double eyelid shape is stable with high satisfaction rate.

Objective:To explore the value of MRI features in predicting the pathological grade of rectal neuroendocrine tumors and to develop a predicting model.Methods:A retrospective analysis was performed on 30 cases of rectal neuroendocrine tumors confirmed by surgery and pathology between 2013 and 2019. All of them underwent plain rectal MRI, DWI and dynamic contrast-enhanced MRI. The clinical features and MRI characteristics (ie. tumor location, maximum tumor diameter, boundary, growth pattern, enhancement of three-staged lesions, and the lymph node metastasis) were analyzed by statistical methods to evaluate the difference between different tumor pathologic grades (G1, G2 and G3). Characteristics with statistical significance were analyzed by collinearity diagnostics, and stepwise regression method was used to select independent predictors. Ordinal logistic regression analysis was then conducted to develop the predicting model.Results:Maximum tumor diameter, tumor boundary, growth pattern, mr-T, mr-N, EMVI, MRF, T2WI signal intensity, tumor enhancement degree in venous phase and distant metastasis were closely correlated with the pathological grade of rectal neuroendocrine tumors ( P<0.001, 0.001, 0.001, <0.001, 0.001, 0.004, 0.024, 0.015, 0.001, and <0.001, respectively). The mr-T and tumor enhancement degree in venous phase were identified as the independent predictors to construct the prediction model. The model got ideal performance in predicting the grades, with the areas under the receiver operating characteristic (ROC) curves (AUCs) of 0.945, 0.624 and 0.896, the sensitivities were 75.0%, 85.7%, and 90.9% and corresponding specificities were 88.9%, 52.6% and 93.3% for G1, G2 and G3 rectal neuroendocrine tumors, respectively. Conclusion:The model based on mr-T and tumor enhancement degree in venous phase can serve as a clinical tool for predicting the pathological grade of rectal neuroendocrine tumors.

Objective:To explore the diagnostic accuracy improved by magnetic resonance imaging (MRI) biomarkers for lymph node metastasis in T1-2 stage rectal cancer before treatment.Methods:Medical records of 327 patients with T1-2 rectal cancer who underwent pretreatment MRI and rectal tumor resection between January 2015 and November 2019 were retrospectively analyzed. Fifty-seven cases were divided into the lymph node metastasis group (N+ group) while other 270 cases in the non-lymph node metastasis group (N-group) according to the pathologic diagnosis. Two radiologist evaluated the tumor characteristics of MRI images. The relationship of the clinical and imaging characteristics of lymph node metastasis was assessed by using univariate analysis and multivariable logistic regression analysis. Receiver operating characteristic (ROC) curve was used to evaluate the diagnostic abilities for the differentiation of N- from N+ tumors.Results:Among the 327 patients, MR-N evaluation was positive in 67 cases, which was statistically different from the pathological diagnosis ( P<0.001). The sensitivity, specificity and accuracy of MRI for lymph node metastasis were 45.6%, 84.8% and 78.0%, respectively. Multivariate regression analysis showed that tumor morphology ( P=0.002), including mucus or not ( P<0.001), and MR-N evaluation ( P<0.001) were independent influencing factors for stage T1-2 rectal cancer with lymph node metastasis. The area under the ROC curve of rectal cancer with lymph node metastasis analyzed by the logistic regression model was 0.786 (95% CI: 0.720~0.852). Conclusions:Tumor morphology, including mucus or not, and MR-N evaluation can serve as independent biomarkers for differentiation of N- and N+ tumors. The model combined with these biomarkers facilitates to improve the diagnostic accuracy of lymph node metastasis in T1-2 rectal cancers by using MRI.

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 explore the diagnostic accuracy improved by magnetic resonance imaging (MRI) biomarkers for lymph node metastasis in T1-2 stage rectal cancer before treatment.Methods:Medical records of 327 patients with T1-2 rectal cancer who underwent pretreatment MRI and rectal tumor resection between January 2015 and November 2019 were retrospectively analyzed. Fifty-seven cases were divided into the lymph node metastasis group (N+ group) while other 270 cases in the non-lymph node metastasis group (N-group) according to the pathologic diagnosis. Two radiologist evaluated the tumor characteristics of MRI images. The relationship of the clinical and imaging characteristics of lymph node metastasis was assessed by using univariate analysis and multivariable logistic regression analysis. Receiver operating characteristic (ROC) curve was used to evaluate the diagnostic abilities for the differentiation of N- from N+ tumors.Results:Among the 327 patients, MR-N evaluation was positive in 67 cases, which was statistically different from the pathological diagnosis ( P<0.001). The sensitivity, specificity and accuracy of MRI for lymph node metastasis were 45.6%, 84.8% and 78.0%, respectively. Multivariate regression analysis showed that tumor morphology ( P=0.002), including mucus or not ( P<0.001), and MR-N evaluation ( P<0.001) were independent influencing factors for stage T1-2 rectal cancer with lymph node metastasis. The area under the ROC curve of rectal cancer with lymph node metastasis analyzed by the logistic regression model was 0.786 (95% CI: 0.720~0.852). Conclusions:Tumor morphology, including mucus or not, and MR-N evaluation can serve as independent biomarkers for differentiation of N- and N+ tumors. The model combined with these biomarkers facilitates to improve the diagnostic accuracy of lymph node metastasis in T1-2 rectal cancers by using MRI.

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.