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.

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 analyze the spatiotemporal characteristics of hand,foot and mouth disease (HFMD) in China, explore the association of socioeconomic, population and health services factors with the incidence of HFMD in China, and provide information for the prevention and control of HFMD. Methods: Bayesian spatiotemporal model was used to fit the data of HFMD, evaluate the spatiotemporal variation of HFMD, and identify the potential association between the risk of HFMD and social, economic, population and health services. Results: From 2011 to 2018, a total of 17 118 050 HFMD cases, including 2 283 deaths, were reported in China. The reported incidence showed a fluctuating increase trend from 2011 to 2014, and a fluctuating decrease trend from 2014 to 2018. Meanwhile, there was a fluctuating decrease trend of mortality rate. The incidence of HFMD had spatial clustering, with the highest incidence in southern China with hot spot and high risk areas, and the lowest incidence in northwestern China where cold spot and low risk areas were found. The risk for HFMD was associated with GDP per capita (RR=3.54), number of industrial enterprises above designated size of 10 000 people (RR=1.61), urbanization rate (RR=3.00), birth rate (RR=2.36), number of beds in medical institutions per 10 000 people (RR=3.40), and green area in parks per capita (RR=0.57). Conclusions: The hotspot area for HFMD prevention and control in China was in the southeast coastal provinces from 2011 to 2018. In order to reduce the incidence of HFMD, it is necessary to increase the green area in parks per capita while accelerating urbanization process.
Humans ; Animals ; Bayes Theorem ; Foot-and-Mouth Disease ; China/epidemiology* ; Hand, Foot and Mouth Disease/epidemiology* ; Menthol

A new teaching mode with the combination of online teaching and flipped class was designed and implemented in the Stomatological College of Nanjing Medical University based on the National Online Open Courses, the Virtual Interactive Network Teaching Platform and the E-learning Network Teaching Platform. The new online course system of orthodontic education was constructed with several components including the process and outcome assessments, the professional literature and knowledge summary reports and the virtual interactive online training. With the informative and convenient online teaching resources and modes, students′ comprehensive abilities of independent learning were improved.

Objective To analyze the epidemic characteristics of tuberculosis (TB) cases in Zhejiang province from 2005 to 2014, and to identify the cluster spots.Methods TB notification data in Zhejiang province from 2005 to 2014 were analyzed at county and district level by using spatial scan statistic analysis method, which was showed on the digital map.Results In zhejiang province from 2005 to 2014, a total of 377 707 cases of patients with tuberculosis were reported.The average annual registration rates of the entire province was 72.61/100 000 (range: 28.85/100 000-182.90/100 000).Spatial analysis identified 14 clusters (RR=1.05-1.62) with statistical significance.Temporal analysis revealed that there were clusters between 2005 and 2009 in terms of the notification data on TB cases (RR=1.27,P=0.001).Spatio-temporal analysis identified 6 clusters (RR=1.19-3.55) with statistical significance.Counties and districts included in the first class cluster were similar by using the two different methods-spatial analysis and spatial-temporal analysis.Conclusions There is a descending trend of TB cases notification rates from western to eastern Zhejiang during the study period.The distribution of the TB case notified is not random at spatial, temporal and spatio-temporal levels.

Aim Toclarifytheeffectofacteosideon proliferation of neural stem cells (NSCs ) from adult mice,as well as the involved signaling pathway.Meth-ods NSCswereisolatedfromthesubventricularzone (SVZ)of adult C57BL/6 mice,then identified by im-munofluorescence staining with Nestin,the marker of NSCs.NSCs were exposed to acteoside (5,10,20,40μmol·L-1 )in absence of mitogen(EGF/bFGF)for 24 h.We employed CCK8 assay to detect NSCs viability and BrdU staining to identify NSCs proliferation.We performed Western blot to quantify the expression level ofp-AktinducedbyacteosideonNSCs.Results With-out mitogen,acteoside increased NSCs proliferation by activating p-Akt,which can be blocked by LY294002, the inhibitor of PI3K/AKT signaling pathway.Conclu-sion ActeosidepromotestheproliferationofNSCsfrom adult mice by activating PI3K/AKT pathway.

Objective To analyze the spatial distribution characteristics ofmultidrug-resistant (MDR) tuberculosis (TB) cases in Zhejiang province in 2010-2012.Methods Data on MDR-TB cases in Zhejiang province were collected and linked to the digital map at the county and district levels.ArcGIS 10.0 software was used for spatial analysis.Results Results from the spatial autocorrelation analysis showed that spatial aggregation appeared in MDR-TB distribution during 2010-2012 while local Moran's I spatial autocorrelation analysis identified several "high incidence regions" (Wuxing,Deqing,Yuhang,Gongshu,Jianggan,Xiaoshan,Yuecheng,Shaoxing Shengzhou,Changshan,Kecheng),and "low incidence region" (Haishu).Through Getis-Ord General G spatial autocorrelation analysis,18 "positive hotspots" (Wuxing,Nanxun,Deqing,Yuhang,Shangcheng,Xiacheng,Gongshu,Jianggan,Binjiang Xiaoshan Xihu,Haining,Yuecheng,Shaoxing,Zhuji,Shengzhou,Kecheng and Suichang) and 11 "negative hotspots" (Nanhu,Haiyan,Cixi,Dinghai,Zhenhai,Jiangbei,Jiangdong,Beilun,Yinzhou,Fenghua,and Yueqing) were identified.Conclusions Spatial analysis on MDR-TB incidence implied the spatial aggregation in Zhejiang province.Data showed that the hotspots with high population density and human movement were under progressive expansion.

Spatial epidemiology and molecular epidemiology have been widely used in the studies of tuberculosis (TB),but each with limitations.Integration of the two methods provides new ideas and methods in TB research.All referenced articles are from CNKI,Wan Fang database,PubMed database and Web of Science database.Method of combining spatial epidemiology and molecular epidemiology has been widely used in determining the local epidemic strains of TB genotype,the transmission mechanism,risk factors of TB,drug-resistant TB,as well as evaluating the effectiveness of TB prevention and control measures.Application of the combined methods is of important significance in the studies of TB,thus worthy to be further introduced to researchers and disease prevention and control workers in this country.

OBJECTIVEThis study aims to investigate the temporal pattern of expression of vascular endothelial growth factor (VEGF) and new bone formation during midpalatal suture expansion osteogenesis for rapid maxillary expansion.

METHODSA total of44 New Zealand white rabbits were randomly assigned to 11 groups, namely, five experimental groups, five control groups, and one control 0 group. A Haas appliance was used for the rapid expansion of the midpalatal suture; rapid expansion was set for 2 weeks and fixed for 4 weeks. The tissue of the maxillary midpalatal suture was harvested on the day of installing rapid expansion (control 0 group), on weeks 1 and 2 for rapid expansion, and on weeks 1, 2, and 4 for fixed (experimental group and control group, respectively). The immunohistochemical method was used to detect distribution and expression of VEGF, and new bone formation was observed with periodic acid-Schiff.

RESULTSHigher VEGF expressions are observed after midpalatal suture distraction osteogenesis. Positive staining for VEGF is mainly noted in the vascular endothelial cells, and the active osteoblasts are at the edge of a newborn trabecular bone. A weak VEGF expression is detected among cells in the control group. The VEGF expression of the experimental group is higher than that of the control group in rapid expansion weeks 1 and 2 and in fixed weeks 1 and 2. The expression of VEGF in the experimental group increases significantly and peaks at fixed week 1, and then gradually decreases. The amount of newly formed bone in the experimental groups is always higher than that in the control group; moreover, it increases significantly and peaks at fixed week 2, and then gradually decreases.

CONCLUSIONThe mechanical strain created by rapid maxillary expansion generates a sequence of VEGF cellular events that lead to increased vascularization and subsequent new bone formation.

Objective This study aims to investigate the temporal pattern of expression of vascular endothelial growth factor (VEGF) and new bone formation during midpalatal suture expansion osteogenesis for rapid maxillary expansion. Methods A total of 44 New Zealand white rabbits were randomly assigned to 11 groups, namely, five experimental groups, five control groups, and one control 0 group. A Haas appliance was used for the rapid expansion of the midpalatal suture; rapid expansion was set for 2 weeks and fixed for 4 weeks. The tissue of the maxillary midpalatal suture was harvested on the day of installing rapid expansion (control 0 group), on weeks 1 and 2 for rapid expansion, and on weeks 1, 2, and 4 for fixed (experimental group and control group, respectively). The immunohistochemical method was used to detect distribution and expression of VEGF, and new bone formation was observed with periodic acid-Schiff. Results Higher VEGF expressions are observed after midpalatal suture distraction osteogenesis. Positive staining for VEGF is mainly noted in the vascular endothelial cells, and the active osteoblasts are at the edge of a newborn trabecular bone. A weak VEGF expression is detected among cells in the control group. The VEGF expression of the experimental group is higher than that of the control group in rapid expansion weeks 1 and 2 and in fixed weeks 1 and 2. The expression of VEGF in the experimental group increases significantly and peaks at fixed week 1, and then gradually decreases. The amount of newly formed bone in the experimental groups is always higher than that in the control group; moreover, it increases significantly and peaks at fixed week 2, and then gradually decreases. Conclusion The mechanical strain created by rapid maxillary expansion generates a sequence of VEGF cellular events that lead to increased vascularization and subsequent new bone formation.