Peptide receptor radionuclide therapy (PRRT) with radiolabeled SSTR2 agonists is a treatment option that is highly effective in controlling metastatic and progressive neuroendocrine tumors (NETs). Previous studies have shown that an SSTR2 agonist combined with albumin binding moiety Evans blue (denoted as ¹⁷⁷Lu-EB-TATE) is characterized by a higher tumor uptake and residence time in preclinical models and in patients with metastatic NETs. This study aimed to enhance the in vivo stability, pharmacokinetics, and pharmacodynamics of ¹⁷⁷Lu-EB-TATE by replacing the maleimide-thiol group with a polyethylene glycol chain, resulting in a novel EB conjugated SSTR2-targeting radiopharmaceutical, ¹⁷⁷Lu-LNC1010, for PRRT. In preclinical studies, ¹⁷⁷Lu-LNC1010 exhibited good stability and SSTR2-binding affinity in AR42J tumor cells and enhanced uptake and prolonged retention in AR42J tumor xenografts. Thereafter, we presented the first-in-human dose escalation study of ¹⁷⁷Lu-LNC1010 in patients with advanced/metastatic NETs. ¹⁷⁷Lu-LNC1010 was well-tolerated by all patients, with minor adverse effects, and exhibited significant uptake and prolonged retention in tumor lesions, with higher tumor radiation doses than those of ¹⁷⁷Lu-EB-TATE. Preliminary PRRT efficacy results showed an 83% disease control rate and a 42% overall response rate after two ¹⁷⁷Lu-LNC1010 treatment cycles. These encouraging findings warrant further investigations through multicenter, prospective, and randomized controlled trials.

Objective To evaluate the short-term efficacy and safety of catheter-directed thrombolysis(CDT)via femoral vein access and via anterior tibial vein access for lower extremity deep vein thrombosis(LEDVT).Methods The clinical data of 86 LEDVT patients,who were treated with CDT via healthy-side femoral vein access or via affected-side anterior tibial vein access at the Second Affiliated Hospital of Nanjing Medical University of China between January 2019 and December 2021,were retrospectively analyzed.Of the 86 patients,via femoral vein access was adopted in 40(FV group)and via anterior tibial vein access was adopted in 46(ATV group).The primary endpoints were the technical success rate and the thrombus removal rate.The secondary endpoints included the operation time and the complications.Results In the FV group and ATV group,the technical success rates were 92.5％and 100％respectively(P=0.097),the thrombus removal rates were(68.9+25.9)％and(78.3±21.0)％respectively(P=0.067),and the differences between the two groups were not statistically significant.The operation time in the FV group and ATV group was(64.1±14.8)min and(72.0±19.9)min respectively(P=0.037),and the difference between the two groups was statistically significant.The incidence of complications in the FV group and ATV group was 22.5％and 10.9％respectively(P=0.145),and the difference between the two groups was not statistically significant.Conclusion CDT therapy,regardless of via femoral vein access or via anterior tibial vein access,can effectively treat LEDVT with quite same clinical short-term efficacy and safety.

Objective:To evaluate the effect of combining contralateral high-frequency transcranial magnetic stimulation (rTMS) with biofeedback-controlled empty swallowing training on dysphagia among stroke survivors.Methods:Eighty dysphagic stroke survivors were divided at random into a control group, a biofeedback group, an rTMS group and a combined treatment group, each of 20. In addition to routine dysphagia rehabilitation, the biofeedback group and the rTMS group received empty swallowing training based on biofeedback or high-frequency rTMS applied to the healthy motor cortex as appropriate. The combined treatment group was given both. The treatment was administered once daily, 5 days a week for 3 consecutive weeks. Before and after the treatment, all of the subjects′ swallowing was evaluated using the penetration aspiration scale (PAS), functional oral intake scale (FOIS) and a standardized swallowing assessment (SSA). The latency and amplitude of the mylohyoid muscle′s motor evoked potentials (MEPs) were also recorded before and after the treatment.Results:After the treatment, significant improvement was observed in the average PAS, FOIS and SSA scores as well as in the latency and amplitude of the MEPs in the four groups. The average results in the combined treatment group were significantly better than in the other 3 groups. The latency of the mylohyoid muscle′s MEP was significantly shorter in the combined group than in the control and biofeedback groups on average, while the amplitude was significantly greater than in the control group.Conclusion:Combining contralateral high frequency rTMS with empty swallowing training based on biofeedback can better improve the swallowing of dysphagic stroke survivors.

Objective:To seek any differential effect of combining repeated transcranial magnetic stimulation (rTMS) with a modified version of constraint-induced movement therapy (mCIMT) on the walking ability of stroke survivors.Methods:Seventy-five stroke survivors were randomly divided into a sham rTMS group, an rTMS group and a combined group, each of 25. In addition to 40 minutes of routine rehabilitation daily, including balance training, transfer training, muscle strength training, and proprioceptive training five times a week for 4 weeks, the sham rTMS group and rTMS group received sham or genuine rTMS. The combined group received 20 minutes of rTMS followed by mCIMT training 30 minutes later. The treatment was performed once a day, 5 days a week for 4 weeks. Before and after the treatment, all groups were evaluated using the Fugl-Meyer lower extremity assessment, the Berg balance scale, a 10-metre walk test and the modified Barthel index.Results:Significant improvement was observed in the average scores of all three groups in all of the assessments. The combined group′s averages were, however, significantly better than those of the other two groups.Conclusion:Supplementing mCIMT with rTMS can better improve the walking and other abilities in the activities of daily living of stroke survivors.

Objective: To understand the current situation and associated factors of cellphone usage and addiction among Chinese children and adolescents, to provide reference for effective prevention and intervention of cellphone addiction. Methods: Using a stratified random sampling approach, 11 213 children and adolescents and their parents from 31 provinces, municipalities and autonomous regions in China were recruited and surveyed. Results: The median of daily mobile phone use time among Chinese children and adolescents were 120.00 minutes, as reported by either children or parents. Child s age( β =0.12), hedonic( β =0.11) and social( β =0.09) cellphone use motivations positively related to time spent on cellphone( P <0.01). Cellphone related parental communication( β =-0.06) and knowledge( β =-0.03), as well as cellphone usage on instrumental( β =-0.04) or self representation( β =-0.16) motivation negatively related to time spent on cellphone( P <0.05). Child s age( β =-0.04), cellphone related parental communication( β =-0.09) and awareness( β =-0.14), cellphone use on instrumental motivation( β =-0.22) were negatively associated with cellphone addiction among children and adolescents( P <0.05). Cellphone related parental monitoring( β =0.07), as well as cellphone usage on self representation motivation( β =0.03) or hedonic motivation( β =0.29) positively related to cellphone addiction in children and adolescents( P <0.05). Conclusion Time spent on mobile phone and mobile phone addiction of Chinese children and adolescents are influenced by various internal and external factors, such as the mobile phone use motivation and parenting style.Future school education should help children develop scientific motivation for mobile phone use. Family education should help parents develop positive parenting behaviors such as communication and awareness, so as to reduce the possibility of improper mobile phone use.

Objective:To analyze the correlation of phthalate metabolites in neonatal umbilical cord blood with birth indicators in Beijing, 2015.Method:From February to July in 2015, 161 pregnant women and their newborns who met the criteria were recruited from the Maternal and Child Health Hospital in Haidian District, Beijing. Questionnaires were used to collect the demographic information of pregnant women such as age, smoking, drinking, and cord blood after delivery. An ultra-high performance liquid chromatography-tandem mass spectrometry was used to determine the concentration of phthalate metabolites in umbilical cord blood. The multiple linear regression model was used to analyze the correlation of phthalate metabolites in umbilical cord blood with the neonatal weight, length, and ponderal index.Result:The age of 161 pregnant women was (30.3±3.0) years. The weight, length and ponderal index of 161 newborns were (3 447.2±413.0) kg, (50.2±1.1) cm, and (26.7±2.2) kg/m 3; 51.6% of newborns (83 cases) were boys. The concentrations of seven phthalate metabolites detected in umbilical cord blood, i.e., mono-methyl phthalate (MMP), mono-ethyl phthalate (MEP),mono-(2-isobutyl) phthalate (MiBP), mono-n-butyl phthalate (MBP), mono-ethylhexyl phthalate (MEHP), mono-(2-ethyl-5-oxohexyl) phthalate (MEOHP), and mono-(2-ethyl-5-carboxypentyl) phthalate (MECPP), was (3.50±0.28), (2.65±0.47), (4.31±0.55), (6.26±0.57), (1.71±0.13), (1.10±0.09) and (0.47±0.06) ng/ml, respectively. The result of multiple linear regression model analysis showed that the concentrations of seven phthalate metabolites were not related to the neonatal weight, length, and ponderal index (all P values> 0.05). Conclusion:The concentrations of phthalate metabolites in neonatal umbilical cord blood are low, and they are not related to the neonatal weight, length, and ponderal index.

Objective:To analyze the correlation of phthalate metabolites in neonatal umbilical cord blood with birth indicators in Beijing, 2015.Method:From February to July in 2015, 161 pregnant women and their newborns who met the criteria were recruited from the Maternal and Child Health Hospital in Haidian District, Beijing. Questionnaires were used to collect the demographic information of pregnant women such as age, smoking, drinking, and cord blood after delivery. An ultra-high performance liquid chromatography-tandem mass spectrometry was used to determine the concentration of phthalate metabolites in umbilical cord blood. The multiple linear regression model was used to analyze the correlation of phthalate metabolites in umbilical cord blood with the neonatal weight, length, and ponderal index.Result:The age of 161 pregnant women was (30.3±3.0) years. The weight, length and ponderal index of 161 newborns were (3 447.2±413.0) kg, (50.2±1.1) cm, and (26.7±2.2) kg/m 3; 51.6% of newborns (83 cases) were boys. The concentrations of seven phthalate metabolites detected in umbilical cord blood, i.e., mono-methyl phthalate (MMP), mono-ethyl phthalate (MEP),mono-(2-isobutyl) phthalate (MiBP), mono-n-butyl phthalate (MBP), mono-ethylhexyl phthalate (MEHP), mono-(2-ethyl-5-oxohexyl) phthalate (MEOHP), and mono-(2-ethyl-5-carboxypentyl) phthalate (MECPP), was (3.50±0.28), (2.65±0.47), (4.31±0.55), (6.26±0.57), (1.71±0.13), (1.10±0.09) and (0.47±0.06) ng/ml, respectively. The result of multiple linear regression model analysis showed that the concentrations of seven phthalate metabolites were not related to the neonatal weight, length, and ponderal index (all P values> 0.05). Conclusion:The concentrations of phthalate metabolites in neonatal umbilical cord blood are low, and they are not related to the neonatal weight, length, and ponderal index.

Objective To evaluate a model for axillary lymph node involvement combining CK19 mRNA with contrast enhanced ultrasound sonography (CEUS) score in operable breast cancer.Methods Operable breast cancer patients planned for sentinel lymph node (SLN) biopsy were enrolled.Preoperative CK19mRNA expressions in peripheral blood and CEUS score of axillary lymph nodes were tested before surgery.In the training set,postoperative sentinel lymph node (SLN) and non-sentinel lymph node (nSLN) pathological results were taken as the gold standard,effective modeling variables were screened,logistic regression was used to establish the prediction model.Parallel control studies were conducted between the validation set and the MSKCC model to evaluate the prediction accuracy and prediction efficiency.Results From Oct 2015 to Nov 2016,359 cases (training set) were enrolled and mathematical formulas for predicting SLN and nSLN were established,respectively.The sensitivity,specificity and AUC of predicting SLN involvement were 91.36％,94.92％ and 0.979 respectively.The sensitivity,specificity and AUC of predicting nSLN metastasis were 91.04％,90.53％ and 0.932 respectively.From Dec 2016 to Jul 2017,219 cases (verification set) were included.The sensitivity of SLN metastasis predicted by the model was 91.84％,the specificity was 96.69％,and the AUC was 0.979,significantly superior to the MSKCC model (0.739).The sensitivity,specificity and AUC of predicting nSLN metastasis were 95.35％,92.73％ and 0.945 respectively,significantly superior to the MSKCC model (0.873).Concolusions Combined with peripheral blood CK19 mRNA and CEUS score,the prediction model for axillary lymph node involvement for operable breast cancer,SLN/nSLN involvement probability can be calculated and qualitative judgment can be made.The overall accuracy and AUC of this model are better than the prediction model of MSKCC.

Objective To investigate the recurrence and survival of postoperative patients with differentiated thyroid carcinoma (DTC) aged from 25 to 59 years.Methods We retrospectively analyzed the clinical data of 36 patients with DTC treated in our hospital from 1996 to 2011,and the recurrence and survival status of the patients were recorded.Kaplan-Meier analysis was carried out to analyze factors that affect the patient's survival.Results Nine patients died of recurrence or metastasis,and the interval between the initial surgery and recurrence ranged from 22 to 46 months.The survival time of the 36 patients ranged from 34 to 135 months with a 10-year survival rate of 75.0％.Kaplan-Meier analysis showed that male patients had a significantly shorter mean survival time than female patients (χ2＝3.164,P=0.041);the median survival time of patients aged 45-59 years was obviously shorter than that of patients aged 25-44 years (χ2＝4.622,P=0.032);the postoperative survival in patients with 131I therapy was significantly longer than those who did not receive the therapy (χ2＝4.527,P=0.033),and was not affected by total excision of the thyroid gland (χ2=0.988,P＝0.320).No significant difference was found in the median survival of patients in different clinical stages (χ2=2.2132,P=0.167).Conclusion In young and middle-aged patients with DTC,postoperative recurrence is the most likely in 2 to 4 years after the surgery.Male patients at 45-59 years of age who do not receive 131I treatment are at high risks of tumor recurrence.

Objective To observe the dynamic changes of Th17/Treg balance in patients following surgical intervention for intracranial aneurysm rupture. Methods The percentage of Th cells and the intracellular IL-17 level, Treg cell percentage and transforming growth factor-β1 (TGF-β1) levels were examined in 73 patients with rupture of aneurysms before and at 24 h, 72 h and 1 week after operation, with 62 patients with unruptured aneurysms and 65 healthy volunteers as the control. The correlations among the immune cells, cytokines and clinical characteristics of the patients (NIHSS, ADL and hospitalization stay) were analyzed. Results Th17 percentage and intracellular IL-17 levels were significantly higher in the patients with ruptured and unruptured aneurysms than in the healthy volunteers, and were significantly higher in patients with ruptured aneurysms than in those with unruptured aneurysms. Treg cell percentage and TGF-β1 level were significantly lower in patients with aneurysms than in the healthy volunteers, and were lower in patients with ruptured aneurysms than in those with uruptured aneurysms (P<0.05). Patients with intracranial aneurysm rupture showed significantly increased Th17 cell percentage and IL-17 level but significantly lowered Treg cell percentage and TGF-β1 at 24 h following the surgery (P<0.05);these changes were reversed significantly at 72 h and 1 week after the surgery. Th17 cell percentage and IL-17 level were positively correlated with NIHSS and the length of postoperative hospital stay but inversely correlated with ADL; Treg cell percentage and TGF-β1 were inversely correlated with NIHSS and hospital stay but positively with ADL (P<0.05). Conclusion In patients with intracranial aneurysms, the systemic immune inflammatory response is highlighted by excessive Th17 cells and insufficient Treg cells, which are closely related with the outcomes of the patients following surgical intervention. Evaluation of Th17/Treg balance and the cytokine levels can help to assess the prognosis of patients with aneurysm rupture.