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.Clinical guidelines for the treatment of ankylosing spondylitis combined with lower cervical fracture in adults (version 2024)
Qingde WANG ; Yuan HE ; Bohua CHEN ; Tongwei CHU ; Jinpeng DU ; Jian DONG ; Haoyu FENG ; Shunwu FAN ; Shiqing FENG ; Yanzheng GAO ; Zhong GUAN ; Hua GUO ; Yong HAI ; Lijun HE ; Dianming JIANG ; Jianyuan JIANG ; Bin LIN ; Bin LIU ; Baoge LIU ; Chunde LI ; Fang LI ; Feng LI ; Guohua LYU ; Li LI ; Qi LIAO ; Weishi LI ; Xiaoguang LIU ; Hongjian LIU ; Yong LIU ; Zhongjun LIU ; Shibao LU ; Yong QIU ; Limin RONG ; Yong SHEN ; Huiyong SHEN ; Jun SHU ; Yueming SONG ; Tiansheng SUN ; Yan WANG ; Zhe WANG ; Zheng WANG ; Hong XIA ; Guoyong YIN ; Jinglong YAN ; Wen YUAN ; Zhaoming YE ; Jie ZHAO ; Jianguo ZHANG ; Yue ZHU ; Yingjie ZHOU ; Zhongmin ZHANG ; Wei MEI ; Dingjun HAO ; Baorong HE
Chinese Journal of Trauma 2024;40(2):97-106
Ankylosing spondylitis (AS) combined with lower cervical fracture is often categorized into unstable fracture, with a high incidence of neurological injury and a high rate of disability and morbidity. As factors such as shoulder occlusion may affect the accuracy of X-ray imaging diagnosis, it is often easily misdiagnosed at the primary diagnosis. Non-operative treatment has complications such as bone nonunion and the possibility of secondary neurological damage, while the timing, access and choice of surgical treatment are still controversial. Currently, there are no clinical practice guidelines for the treatment of AS combined with lower cervical fracture with or without dislocation. To this end, the Spinal Trauma Group of Orthopedics Branch of Chinese Medical Doctor Association organized experts to formulate Clinical guidelines for the treatment of ankylosing spondylitis combined with lower cervical fracture in adults ( version 2024) in accordance with the principles of evidence-based medicine, scientificity and practicality, in which 11 recommendations were put forward in terms of the diagnosis, imaging evaluation, typing and treatment, etc, to provide guidance for the diagnosis and treatment of AS combined with lower cervical fracture.
3.Screening of miRNA biomarkers in serum exosomes of patients with thyroid nodules at different iodine levels
Wenyuan CAO ; Hongjian ZHAO ; Hao XING ; Hui ZHANG ; Wei KONG ; Qinghua LIU ; Fengyan YIN ; Qian HE ; Weijia XING
Chinese Journal of Clinical Laboratory Science 2024;42(1):62-66
Objective To comapre and analyze the differences and commonalities of expression profiles of serum exosomal microRNA between patients with thyroid nodules and healthy persons at different iodine levels,and then provide evidence for screening early diag-nostic markers of thyroid nodules at different iodine levels.Methods The peripheral blood samples from 10 patients with thyroid nod-ules and healthy volunteers at different iodine levels were collected.Their serum iodine levels were measured by the arsenic cerium cat-alytic spectrophotometry.Serum exosomal microRNA were extracted and the expression levels of microRNA were determined by the high-throughput sequencing technology.The differential target genes were predicted and further performed Gene ontology(GO)analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)analysis.Results Compared with healthy volunteers,there were 6 downreg-ulated miRNAs in the patients with thyroid nodules at different iodine levels,namely miR-324-5p,miR-6511b-3p,miR-9903,miR-550a-3p,miR-5001-3p,and miR-3688-3p.Differentially expressed exosomal microRNA could regulate the MAPK signaling path-way,PI3K-AKT signaling pathway,VEGF signaling pathway,and NF-κB signaling pathway.Conclusion Six differentially expressed microRNAs is identified,which may serve as biological markers for the early diagnosis of thyroid nodules at different iodine levels.
4.Clinical guidelines for the diagnosis and treatment of osteoporotic thoracolumbar vertebral fracture with kyphotic deformity in the elderly (version 2024)
Jian CHEN ; Qingqing LI ; Jun GU ; Zhiyi HU ; Shujie ZHAO ; Zhenfei HUANG ; Tao JIANG ; Wei ZHOU ; Xiaojian CAO ; Yongxin REN ; Weihua CAI ; Lipeng YU ; Tao SUI ; Qian WANG ; Pengyu TANG ; Mengyuan WU ; Weihu MA ; Xuhua LU ; Hongjian LIU ; Zhongmin ZHANG ; Xiaozhong ZHOU ; Baorong HE ; Kainan LI ; Tengbo YU ; Xiaodong GUO ; Yongxiang WANG ; Yong HAI ; Jiangang SHI ; Baoshan XU ; Weishi LI ; Jinglong YAN ; Guangzhi NING ; Yongfei GUO ; Zhijun QIAO ; Feng ZHANG ; Fubing WANG ; Fuyang CHEN ; Yan JIA ; Xiaohua ZHOU ; Yuhui PENG ; Jin FAN ; Guoyong YIN
Chinese Journal of Trauma 2024;40(11):961-973
The incidence of osteoporotic thoracolumbar vertebral fracture (OTLVF) in the elderly is gradually increasing. The kyphotic deformity caused by various factors has become an important characteristic of OTLVF and has received increasing attention. Its clinical manifestations include pain, delayed nerve damage, sagittal imbalance, etc. Currently, the definition and diagnosis of OTLVF with kyphotic deformity in the elderly are still unclear. Although there are many treatment options, they are controversial. Existing guidelines or consensuses pay little attention to this type of fracture with kyphotic deformity. To this end, the Lumbar Education Working Group of the Spine Branch of the Chinese Medicine Education Association and Editorial Committee of Chinese Journal of Trauma organized the experts in the relevant fields to jointly develop Clinical guidelines for the diagnosis and treatment of osteoporotic thoracolumbar vertebral fractures with kyphotic deformity in the elderly ( version 2024), based on evidence-based medical advancements and the principles of scientificity, practicality, and advanced nature, which provided 18 recommendations to standardize the clinical diagnosis and treatment.
5.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.
6.Overlap syndrome: a case report of extensive chronic graft-versus-host disease and literature review
Yanxia ZHOU ; Shenghui LUO ; Weixuan QIN ; Hongjian YE ; Ying WANG ; Wenfang CHEN ; Zhijian LI ; Wei CHEN ; Xin WANG
Chinese Journal of Nephrology 2023;39(11):851-857
The paper reported a case of a young male patient, with graft-versus-host disease (GVHD) multi-organ involvement lesions after allo-hematopoietic stem cell transplantation. The patient had diverse clinical manifestations, and overlapping acute and chronic disease processes. Acute GVHD were mainly hyperbilirubinemia, with or without elevated transaminase, bloody watery stools; chronic GVHD were highlighted by extensive skin depigmentation, oral mucosal ulcer, sick nails, etc., and chronic signs, such as membranous nephropathy, polyserositis and pulmonary restrictive ventilatory insufficiency. The diagnosis of chronic GVHD mainly relies on medical history combined with clinical manifestations, and it's needed to exclude infections, drugs and tumors. Besides, the rate of missed diagnosis and misdiagnose is high, and it requires multidisciplinary diagnosis and treatment. Combined with the literature review, it indicates that there is a greater risk of GVHD in the male recipient with female donor, and peripheral blood stem cell transplant patients have a higher incidence than bone marrow transplant patients after hematopoietic stem cell transplantation, but the effect of the graft-versus-leukemia exists. Currently, glucocorticoids therapy with or without calcineurin inhibitors are the first-line treatment for GVHD, but the overall prognosis is poor.
7.Contents of 12 soil metal elements in the plague high incidence area and resting area in the plague natural foci of Qingnan region of Qinghai Province
Youwen WEI ; Hongjian CHEN ; Xianya MENG ; Xue WANG ; Cuiling LA ; Kuizhang ZHOU ; Baoyu MI ; Qian LI ; Ying MA
Chinese Journal of Endemiology 2021;40(12):947-952
Objective:To investigate the contents of soil metal elements in the plague high incidence area and resting area in the plague natural foci of Qingnan region in Qinghai Province, and to compare and analyze the differences of the contents of soil metal elements between the two areas.Methods:A total of 69 soil samples were collected from 11 sites in the plague high incidence area (Yushu Prefecture) and resting area (Guoluo Prefecture) in Qingnan region, including 39 samples from high incidence area and 30 samples from resting area. The contents of 12 soil metal elements, such as iron (Fe), magnesium (Mg), calcium (Ca), barium (Ba), cobalt (Co), copper (Cu), manganese (Mn), lead (Pb), rubidium (Rb), titanium (Ti), vanadium (V) and zinc (Zn), were measured by X-ray fluorescence spectrometry and SPSS 20.0 software was used for Spearman correlation and other statistical analysis.Results:The contents of Fe and Ca in the soil of the plague natural foci of Qingnan region were relatively high. The contents of 12 soil metal elements in the high incidence area were significantly higher than those in the resting area ( P < 0.01 or < 0.05). There were statistical significant differences in the contents of Mg, Ca, Ba, Mn, Pb and Zn in the soil among the sample plots of the plague high incidence area ( P < 0.01 or < 0.05). There were statistical significant differences in the contents of Fe, Mg, Ca, Rb and Ti in the soil among the sample plots of the plague resting area ( P < 0.05 or < 0.01). Except for Mg and Ca, Fe was positively correlated with other metal elements in the high incidence area and resting area ( P < 0.01 or < 0.05), and Fe was strongly positively correlated with Rb, Ti and V ( r = 0.780 - 0.838). Mg was only positively correlated with Ca in the high incidence area and resting area ( P < 0.01). Ca was negatively correlated with Mn, Pb, Rb, Ti, V and Zn in the high incidence area, and with Rb and Zn in the resting area ( P < 0.01 or < 0.05). The rest of the metal elements were mostly positively correlated in the high incidence area and resting area. Conclusions:The contents of Fe and Ca are rich in the plague natural foci of Qingnan region in Qinghai Province. There are correlations among most soil metal elements in the high incidence area and resting area. The correlation between the contents of soil metal elements in the plague natural foci and the epidemic of plague is worth further exploring.
8.Association of vitamin D nutritional status with calcaneal bone mineral density in school-age children: a prospective cohort study
Haibo LI ; Xiaoyuan ZHAO ; Wei HONG ; Dongqing HOU ; Zhongxin ZHU ; Zhaocang YU ; Hongjian WANG ; Aiyu GAO ; Hong CHENG ; Jie MI
Chinese Journal of Epidemiology 2021;42(3):462-468
Objective:To investigate the relationships between vitamin D nutritional status and the calcaneal bone mineral density (BMD) in children.Methods:Data were obtained from School-based Cardiovascular and Bone Health Promotion Program. In 2017, a total of 15 391 children aged 6-16 years in Beijing selected through stratified cluster sampling were included in the baseline survey. A follow-up investigation was conducted in 2019. The questionnaire survey, detection of serum 25-hydroxyvitamin D [25(OH)D] level and ultrasound measurement of calcaneal BMD were conducted. Multivariable linear and logistic regression models were used to analyze the relationships between baseline vitamin D nutritional status and the follow-up calcaneal BMD.Results:A total of 10 914 children aged (11.5±3.3) years (boys accounting for 49.6%) were included in the analysis. The average 25(OH)D level was (35.4±12.0) nmol/L, and the deficiency rate was 36.1%. After the adjustment for age, gender, body mass index, smoking status, alcohol use status, dairy products intake, vitamin D supplement, calcium supplement, physical activity, pubertal development, and baseline calcaneal BMD Z-score, for per 10 nmol/L increase in 25(OH)D, the follow-up calcaneal BMD Z-score increased by 0.01( P=0.041), and the OR(95% CI) of decreased calcaneal BMD Z-score after 2 years was 0.96 (0.93-1.00)( P=0.030). Compared with vitamin D adequacy, the follow-up calcaneal BMD Z-score of children with vitamin D insufficiency and deficiency decreased by 0.03( P=0.307) and 0.06 ( P=0.046), and the risk of decreased calcaneal BMD Z-score after 2 years increased by 15%( P=0.037) and 21%( P=0.006), respectively ( P for trend<0.05). Conclusions:Vitamin D nutritional status was closely related to calcaneal BMD, and children with adequate vitamin D nutritional status tended to obtain higher BMD. Children and adolescents are encouraged to maintain sufficient vitamin D levels, strengthen nutrition and exercise to promote bone health.
9.Complications after laparoscopic pancreaticoduodenectomy and establishment of predicting model for postoperative pancreatic fistula
Haoran WU ; Heng ZHANG ; Xiaohui DUAN ; Jianhui YANG ; Zhen′an TIAN ; Hongjian ZHANG ; Fahui CHENG ; Rongguang WEI ; Yangjianpei XU ; Xianhai MAO
Chinese Journal of General Surgery 2020;35(11):838-842
Objective:To explore the risk factors for overall complications after laparoscopic pancreaticoduodenectomy(LPD) and to establish postoperative pancreatic fistula prediction model for LPD.Methods:The clinical data of 176 patients undergoing LPD from Jan 2014 to Mar 2018 were retrospectively analyzed.Results:One died within 30 days. Five patients underwent reoperation. Seventy-three patients (41%) had complications including pancreatic fistula in 30 cases(17.0%), postoperative hemorrhage in 16 (9.1%); bile leakage in 10 (5.7%); abdominal infection in 6 (3.4%); wound infection in 4 (2.2%); pulmonary infection in 4 (2.2%); gastric emptying disorder in 3 (1.7%). Age, intraoperative blood loss, diabetes mellitus were risk factors for overall postoperative complications of LPD(all P<0.05); Age, male gender, pancreatic duct diameter, pancreas texture, lesion size were risk factors for pancreatic fistula after LPD(all P<0.05). Conclusions:Age, intraoperative blood loss, diabetes mellitus were risk factors for overall postoperative complications of LPD; Age, male gender, pancreatic duct diameter, pancreas texture, and lesion size were risk factors for pancreatic fistula after LPD.
10.A prospective cohort study on the associations between vitamin D nutritional status and cardiometabolic abnormities in children
Pei XIAO ; Xiaoyuan ZHAO ; Wei HONG ; Dongqing HOU ; Zhaocang YU ; Liange WANG ; Hongjian WANG ; Aiyu GAO ; Hong CHENG ; Jie MI
Chinese Journal of Epidemiology 2020;41(12):2059-2065
Objective:To investigate the relationships between vitamin D nutritional status and the risks of cardiometabolic abnormities in children.Methods:Data were obtained from the School-based Cardiovascular and Bone Health Promotion Program. In 2017, a total of 15 391 children aged 6-16 years in Beijing were selected by using a stratified cluster sampling method in the baseline survey. A Follow-up investigation was conducted in 2019. Log-binomial regression was used to analyze the relationships between baseline vitamin D nutritional status and the risks of cardiometabolic abnormities (obesity, hypertension, hyperglycemia, and dyslipidemia).Results:A total of 10 482 participants were involved in the study. The average vitamin D level was (35.6 ± 12.0) nmol/L, and the deficiency rate was 35.1%. The 2-year cumulative incidence rates of obesity, hypertension, hyperglycemia, high TC, high LDL-C, low HDL-C, high TG, and high non-HDL-C were 4.3%, 10.8%, 8.5%, 3.1%, 2.5%, 3.4%, 2.5%, and 3.9% respectively. After the adjustment of potential confounding factors, children with vitamin D inadequacy or deficiency had higher risks of high TC [ RR (95 %CI): inadequacy, 2.06 (1.19-3.58); deficiency, 2.80 (1.61-4.89)], high LDL-C [ RR (95 %CI): inadequacy, 1.67 (1.02-2.73); deficiency, 1.99 (1.19-3.33)], and high non-HDL-C [ RR (95 %CI): inadequacy, 2.00 (1.26-3.17); deficiency, 2.45 (1.53-3.92)] compared with children with adequate vitamin D, and the risks of them increased with the decrease of vitamin D level (trend P<0.05). The gender-stratified analysis showed that vitamin D deficiency was remained associated with high TC [ RR (95 %CI): boy, 2.64 (1.19-5.87); girl, 3.13 (1.43-6.83)] and high non-HDL-C [ RR (95 %CI): boy, 2.58(1.40-4.77); girl, 2.31 (1.10-4.84)]. Conclusions:The risks of abnormal TC, LDL-C, and non-HDL-C were inversely associated with vitamin D level. Maintenance of adequate vitamin D status in children may contribute to the early prevention of cardiovascular diseases.

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