1.Safety, dosimetry, and efficacy of an optimized long-acting somatostatin analog for peptide receptor radionuclide therapy in metastatic neuroendocrine tumors: From preclinical testing to first-in-human study.
Wei GUO ; Xuejun WEN ; Yuhang CHEN ; Tianzhi ZHAO ; Jia LIU ; Yucen TAO ; Hao FU ; Hongjian WANG ; Weizhi XU ; Yizhen PANG ; Liang ZHAO ; Jingxiong HUANG ; Pengfei XU ; Zhide GUO ; Weibing MIAO ; Jingjing ZHANG ; Xiaoyuan CHEN ; Haojun CHEN
Acta Pharmaceutica Sinica B 2025;15(2):707-721
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.
2.The effects of combining transcranial magnetic stimulation with biofeedback in retraining the swallowing of stroke survivors with dysphagia
Qian XU ; Zhenzhen HAN ; Dongyan ZHU ; Liang WANG ; Fang CAO ; Jiajia ZHAI ; Hongjian LU
Chinese Journal of Physical Medicine and Rehabilitation 2024;46(1):17-22
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.
3.The short-term efficacy and safety of catheter-directed thrombolysis via femoral vein and anterior tibial vein access for acute lower extremity deep vein thrombosis
Yanyan QU ; Zhiqin WEI ; Hongjian SHI ; Liang ZHOU ; Zhen GAN
Journal of Interventional Radiology 2024;33(7):774-779
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.
4.The effects of combining repeated transcranial magnetic stimulation with modified constraint-induced movement therapy on walking ability after a stroke
Dongyan ZHU ; Hongjian LU ; Zhidong HUANG ; Liang WANG ; Jiajia ZHAI ; Qian XU ; Zhenzhen HAN ; Yuejiao CAO ; Huiyuan JI
Chinese Journal of Physical Medicine and Rehabilitation 2023;45(9):781-785
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.
5.Cellphone usage and addiction among Chinese children and adolescents and related factors
ZHOU Nan, WANG Shaofan, ZHU Xichun, WANG Yi, CHEN Ling, CAO Hongjian, LIANG Yue, ZHANG Jintao
Chinese Journal of School Health 2022;43(8):1179-1184
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.
6.A study on the correlation of phthalate metabolites in umbilical cord blood of 161 newborns with birth indicators in Beijing
Hongjian MIAO ; Lei ZHANG ; Jianqiang LAI ; Liang SUN ; Yunfeng ZHAO ; Jingguang LI
Chinese Journal of Preventive Medicine 2020;54(7):768-773
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.
7.A study on the correlation of phthalate metabolites in umbilical cord blood of 161 newborns with birth indicators in Beijing
Hongjian MIAO ; Lei ZHANG ; Jianqiang LAI ; Liang SUN ; Yunfeng ZHAO ; Jingguang LI
Chinese Journal of Preventive Medicine 2020;54(7):768-773
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.
8.CK19 mRNA in peripheral blood combined with contrast-enhanced ultrasound: the predictive value of axillary lymph node involvement in breast cancer
Xingfei YU ; Lingyan ZHOU ; Chen YANG ; Bo CHEN ; Chen WANG ; Chenlu LIANG ; Haojun XUAN ; Xiping ZHANG ; Daobao CHEN ; Yang YU ; Jian HUANG ; Hongjian YANG
Chinese Journal of General Surgery 2019;34(6):483-488
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.
9.Cephalocaudal relationship ofabdominal aortic bifurcation relative toumbilicus and iliac crest vertex:a comparative study from imaging anatomical prospective
Hongjian JIAN ; Tao ZHONG ; Minhai ZHANG ; Fang YU ; Rugang ZHENG ; Guodong LIANG ; Gang WU
The Journal of Practical Medicine 2017;33(6):920-923
Objective To studythe cephalocaudal relationship ofabdominal aortic bifurcation relative toumbilicus and iliac crest vertex and their correlations with abdominal adipose tissue thickness and age. Methods The vertical distances,cephalocaudal relationship and other related anatomic parameters of aortic bifurcation relative to umbilicus and iliac crest vertex in 108 patientswere measured by consecutive abdominal CT scanning. The correlations of the acquired data with abdominal adipose tissue thickness and age were analyzed using Pearson correlation coefficient. Results Umbilicus was located at cephalad to aortic bifurcation in 67 patients(62.0%), caudal in 34(31.4%)andthe same level in 7(6.5%),with the vertical distance of(4.53 ± 17.51)mm to the aortic bifurcation. No statistically significant relationship was found between abdominal adipose tissue thickness(P>0.05) or age(P>0.05). Iliac crest vertex relative to aortic bifurcationwas located at cephalad,caudal and the same level in 31,71 and 6 patients,taking up 28.7%,65.7%and 5.6%,respectively. Its vertical distance to the bifurcation was(-6.34 ± 14.49)mm,nonrelated with abdominal adipose tissue thickness(P>0.05),but positively correlated with age(P<0.01). The difference in the cephalocaudal relationship of aortic bifurcation relative to umbilicus and iliac crest vertex was statistically significant(P<0.01). Conclusion Compared with iliac crest vertex,umbilicus is an important landmark of locating abdominal aortic terminal occlusion position in vitro because it mostly lies cephalad to aortic bifurcation in the front of the body,not easy to vary with abdominal adipose tissue thickness and age.
10.Novel Tetrapeptide Hydrophilic Interaction Chromatography Materials for High-efficiency Glycopeptide Enrichment
Cheng CHEN ; Hongxi WANG ; Hongjian KANG ; Yao YAO ; Guangyan QING ; Xiuling LI ; Xinmiao LIANG
Chinese Journal of Analytical Chemistry 2017;45(8):1149-1154
In this study, a novel tetrapeptide hydrophilic interaction chromatography (HILIC) material was synthesized, and corresponding enrichment method for glycopeptides was developed.The tetrapeptide modified silica gel materials (denoted as Poly-DAPD) were synthesized by atom-transfer radical-polymerization (ATRP) and characterized by N2 adsorption desorption and thermometer, thermal gravimetric analyzer (TGA) and X-ray photoelectron spectrometer (XPS).The characterization results indicated that tetrapeptide had been successfully synthesized on silica gel.Poly-DAPD materials showed high enrichment selectivity toward fetuin glycopeptides under solid-phase extraction (SPE) mode.Comparing with commercialized ZIC-HILIC in glycopeptides enrichment of fetuin digest which mixed with 5 mole ratio of albumin bovine (BSA), the as-prepared materials showed higher selectivity in both aspects of the identified number of glycopeptides and anti-interference property.The SPE results demonstrated that the tetrapeptide-based HILIC materials could be a potential tool in large-scale glycosylation analysis.


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