Objective To study the effect of Coxsackie virus B3 (CVB3) infection on islet cells in vitro, and to explore the mechanism of islet cells caused by CVB3. Methods Bone marrow mesenchymal stem cells( BMSCs) were separated from the bone marrow and cultured. Then they were induced to differentiate into islet-like cells using nicotinamide and mercaptoethanol. Differentiated cells were detected by morphology , special staining and RT-PCR. Observe CVB3 infection on islet cells under inverse microscope and detect the specific gene fragment by RT-PCR. Results BMSCs showed half suspended shape and gathered to form a cluster after induction. Cells became red brown by dithizone specific staining. RT-PCR also proved the existence of mRNA expressing insulin. Infected islet cells appeared typical pathological changes like shrinks, refraction decreases. RT-PCR detected the desired specific gene fragment of 299 bp in infected islet cells. Conclusion CVB3 can directly injury islet cells, and damage the function of islet cells of secreting insulin.

Objective:To evaluate the efficacy of 125I interstitial brachytherapy in the treatment of local advanced parotid adenoid cystic carcinoma (ACC), and to analyze prognostic factors affecting treatment outcome, in order to provide references for the treatment of local advanced parotid adenoid cystic carcinoma. Methods:Patients with histology-confirmed ACC of the parotid who received 125I interstitial brachytherapy in Peking University Hospital of Stomatology between Aug 2007 and Jan 2018 were included.Prognostic factors affecting overall survival (OS), progression-free survival (PFS), and local control rate (LCR) were analyzed.Meanwhile, distant metastases as well as acute and long-term radiological toxicities were described. Results:A total of 16 patients (11 females, mean age 55.4 years) of stage cT 4bN 0M 0 who received definitive 125I interstitial brachytherapy were included.The median follow-up period was 41.5 months (8-104 months), and the 1-, 3- and 5-year OS were 86.7%, 72% and 54%, respectively.Five patients suffered from local recurrence, the 1-, 3- and 5-year LCR were 93.7%, 80% and 68.7%, respectively, and the 1-, 3- and 5-year PFS were 74%, 53%, and 18.9%, respectively.Nine cases developed distant metastases.Among them, intracranial and pulmonary metastases took place the most frequently and six patients who had skull base invasion developed multi-organ metastases.An encased carotid artery was an independent prognostic factor for distant metastases (HR=12, P=0.045). Severe radiological toxicities were observed in eight patients (8/16, 50%), including radio-dermatitis, hearing loss, progressive trismus, and eye toxicities. Conclusions:The 5-year LCR in patients treated with definitive 125I interstitial brachytherapy for local advanced ACC of the parotid was 68.7%, and skull base invasion and an encased carotid artery were independent adverse prognostic factors of bad prognosis and multi-organ metastases.

Objective:To explore and evaluate the accuracy, conformity, and clinical application value of digital surgical techniques in guiding 125I seed implantation in the brachytherapy of deep head and neck tumors. Methods:Twelve patients with deep head and neck tumors who received brachytherapy of radioactive 125I seed implantation were selected for the study.The locations of the implantation needles and seeds were designed based on CT images before the operation.A digital positioning model was built according to the treatment plan to accurately import the planned locations of implantation needles into the surgical navigation system.Meanwhile, an individualized puncture guidance template was designed and printed according to the patients′ facial profiles as well as the locations and directions of the implantation needles.During the operation, the template was put in place under the guidance of the navigation system and meanwhile, the implantation needle puncture and radioactive seed implantation were conducted under the joint guidance of the visual needle path and real-time implantation needle locations in the navigation system and template guidance holes.The locations of the implantation needle and the seeds were validated by CT scan and the dose distribution in target areas was calculated.Adverse reactions such as hematoma, pain, infection, nonunion of puncture sites, and tumor cell implantation were observed during and after the operation. Results:All 12 patients successfully received implantation needle puncture and radioactive seed implantation under the guidance of the digital surgical techniques, achieving excellent effects of real-time visualization guidance.Meanwhile, the locations and number of the implantation needles and seeds were consistent with the treatment plan and were distributed evenly.Furthermore, according to postoperative verification, D90 ranged from 83.7 Gy to 131.0 Gy, with an average of 107.5 Gy; V100 was 89.6%-99.3%, with an average of 94.6%, and V150 ranged from 40.2% to 58.9%, averaging 47.8%.No serious adverse reactions were observed during and after the operation. Conclusions:With digital surgical techniques, the surgical navigation system and 3D-printed individualized puncture guidance template jointly guided the implantation needle puncture and 125I seed implantation, improving the accuracy and conformity of the brachytherapy.Therefore, they have clinical application value in head and neck brachytherapy, especially in deep areas with complex anatomical structures.

Objective To evaluate the treatment of malignant submandibular gland tumors with surgery combined with 125I radioactive implantation.Methods Thirty-two patients with malignant submandibular gland tumors were treated with surgery combined with 125I seed implantation from December 2005 to December 2012.All of the 32 patients with primary disease were treated by excision of the submandibular gland and neoplasm.None of the patients received wide excision or neck dissection without the evidence of the neck metastases.The planning targets was based on computerized tomography (CT)images,tumors site,extent and pathologic type.The matched peripheral dose (mPD) was 90-110 Gy.Recurrence-free survival (RFS),overall survival (OS) rates and side effects were retrospectively reviewed.Results Totally 32 patients received 1394 radioactive seeds implantation,radioactive seeds and dose distributed were well in all patients.All patients were followed for 15-126 months (mean of 64 months),with 5 recurrence,5 distant metastases,and 4 patients who died of disease.The 3-and 5-year RFS were 93.1％ and 87.9％,and OS rates were 93.3％ and 84.5％,respectively.No severe complications were observed during follow-up.Conclusions The excision of the neoplasm and the submandibular gland,combined with 125I seed implantation brachytherapy was an effective modality for the treatment of malignant submandibular gland tumors.

Objective To evaluate the efficacy of 125Ⅰ brachytherapy alone for the treatment of recurrent parotid gland carcinoma.Methods Recurrent parotid gland carcinoma patients (n =24) treated by 125Ⅰ brachytherapy alone between 2006 and 2013 at Peking University Hospital of Stomatology were enrolled in this retrospective study.All patients underwent surgery or radiotherapy.The local control rate,survival rate,and side effects were evaluated.Results The median follow-up time was 21 months (range,4-59 months).Among the 24 patients,6 had local failure and 10 died during the follow-up period.The 1-and 3-year overall survival rates,progression-free survival rates,local control rates were 74.8％ and 39.3％,74.8％ and 31.5％,82.0％ and 69.4％,respectively.No grade 3 or over radiation injury was found.Conclusions 125Ⅰ seed brachytherapy alone could provide an ahernative treatment method for inoperable recurrent parotid gland carcinoma patients.

Background and purpose:Integrinαvβ3 receptor plays an important role in promoting, sustaining and regulating the angiogenesis. It is overexpressed on neovascular endothelial cells and tumor cells. RGD peptide specifically binds to integrinαvβ3, which could evaluate growth status and invasiveness of tumor. This study aimed to investigate the biodistribution in healthy KM mice and micro PET/CT imaging in U87MG tumor-bearing mice of 18F-E[c(RGDfK)2]. Methods: 18F-E[c(RGDfK)2] was produced using an automated synthesis module via a simple one-step 18F-labeling strategy of the precursor 4-NO2-3-TFMBz-E[c(RGDfK)2]. The percentage activity of injection dose per gram of tissue (%ID/g) was calculated at 0.5, 1, 2, 4 h post injection of the probe. Micro PET/CT images of U87MG tumor-bearing nude mice with or without 18F-E[c(RGDfK)2] blocking were acquired at each time point. Results: The labeling efficiency and radiochemical purity of 18F-E[c(RGDfK)2] were 10% and 98%, respectively. 18F-E[c(RGDfK)2] was excreted via renal route, with a high blood clearance. The other organs had background-level activity accumulation. At 1 h, the%ID/g of kidney, liver, intestine, muscle and blood was (1.02±0.16)%ID/g,(0.24±0.06)%ID/g, (0.35±0.03)%ID/g, (0.13±0.03)%ID/g and (0.11±0.03)%ID/g 18F-E[c(RGDfK)2] had initial high tumor uptake [(5.2±0.56)%ID/g] and good tumor-to-background contrast (5.36) at 1 h post injection. Tumor uptake for blocking group was lower than those without blocking, and T/M reduced to 1.57. Conclusion: 18F-E[c(RGDfK)2] appears a promising PET molecular imaging probe targeting integrin αvβ3, with high tumor uptake. It could be suitable for prognosis evaluation of integrin-positive tumor, selection of vascular targeting therapy and therapy effect monitoring.

Background and purpose: One of the main mechanism of chemotherapy is inducing tuomr apoptosis. Molecular imaging can allow noninvasively and dynamically monitor tumor apoptosis in vivo, and help to drug screening and therapeutic evaluation. The purpose of this study was to evaluate the feasibility of 18F-SFB-Annexin B1 in detecting apoptosis at an early phase after chemotheraphy. Methods:Annexin B1 was labeled with 18F using SFB as a chelating agent. Tissue distribution of 18F-SFB-Annexin B1 was studied in healthy mice by the dissection method. W256 tumor-bearing rats were injected with 18F-SFB-Annexin B1 intravenously at 24 h after the treatment of cyclophosphamide (CTX 200 mg/kg) or saline. Then imaging was acquired at 1, 2, 3, and 4 h postinjection on a PET/CT, and the tumor-to-muscle ratio of SUVmax (T/M) and the AI from TUNEL testing were compared. Results: 18F-SFB-Annexin B1 had a radiochemical pruity (RCP)>95%. Biodistribution of this probe showed a predominant uptake in the kidney, then was liver, spleen, and myocardium, rapid clearance from blood and urinary was observed. The radios of T/M were 4.38±0.56, 6.75±1.16, 6.44±1.12, 4.81±0.17, respectively at 1, 2, 3, 4 h post injection of the chemotherapy group, much higher than that of the saline group (2.35±0.14, 2.99±0.55, 3.04±0.41, 2.33±0.47, respectively). The differences between the two groups were significant (F=23.790, 16.913, 14.046, 77.517, respectively, all P<0.05). TUNEL staining revealed that chemotherapy treatment significantly increased the percentage of apoptosis cells with an AI of (21.00±0.04)%in the chemotherapy group, higher than that in the saline group (8.58±0.01)%, the difference was significant (F=21.539, P<0.05). The radios of T/M were significantly correlated with the values of AI (r=0.91, P<0.05). Conclusion: 18F-SFB-Annexin B1 can be used to apoptosis imaging and early therapeutic evaluation in vivo because it can reflect apoptosis at an early stage after chemotheraphy.

Objective To evaluate the feasibility of individual template assisting permanent interstitial brachytherapy for skull base region.Methods From August 2010 to June 2012,20 patients with recurrent malignancies of skull base region received 125I seed permanent implantation.Before implanting,all patients underwent CT scan,the data were stored in Dicom format and imported into brachytherapy treatment planning system (BTPS).The preplan were finished by BTPS.Then,the digital model based on virtual needle and skin CT slices was reconstructed by Mimics and Geomagic.According to the digital model,the individual template was made from medical light-cured resin using rapid forming machine.During implanting,needles were inserted under the individual template assistance and 125I seeds were implanted according to preplan.After implanting,implantation quality was evaluated by 2D and 3D CT images and BTPS.The needles and seed distribution were observed.The actual dose distribution of target volumes D90,V100 and V150 was calculated.The complications were recorded within 72 hours.Results Interstitial implantation of 20 patients were performed successfully and efficiently under the individual template assistance without serious complications.Because of containing the virtual needle positioning and face surface feature information at the same time,the individual template significantly improved precision of needle location and orientation.The actuarial median number of 125I seeds implanted was 70 (range,20-172),and actuarial median D90,V100 and V150 was 181.6 Gy (127.4-279.6 Gy),98.2％ (94.6％-100％),43.2％ (24.3％-52.2％),respectively.The seed distribution and dosimetric quality were well controlled.Conclusions The method of individual template assisting permanent interstitial brachytherapy for skull base region is feasible,which can improve the accuracy of needle position placement.

Objective:To investigate clinical features of distant metastases ( DM ) and analyze clinico-pathologic risk factors associated with DM from salivary gland carcinomas after being treated by surgery combined with 125 I internal brachytherapy. Methods: Between October 2001 and March 2010, 197 pa-tients with salivary gland carcinoma were treated by surgery combined with 125 I internal brachytherapy and had follow-up for 2 years or more. Univariate and multivariate analyses were performed to evaluate clini-copathologic risk factors that might influence the risk of distant metastases. Results:DM occurred in 28 of 197 patients (14. 2%). The commonest site of distant metastases overall was the lung 89. 3% (25/28), followed by bones 17. 9% (5/28) and liver (4/28). DM developed after an average interval of (44. 2 ± 45. 8) months from the time of initial diagnosis, and the mean interval was 64 months. The average time to death after the diagnosis of DM was only (9. 7 ± 13. 4) months, and the mean time was 12 months. The 3-year locoregional control rate and survival rate were 90. 8%, and 87. 8% respectively,and the 5-year ones 84. 0% and 81. 0%, respectively. Univariate analyses revealed that the risk of distant metasta-ses was significantly influenced by locoregional tumor failure (F=26. 997,P<0. 01) and histologic dif-ferentiation (F=1. 592,P<0. 01). Multivariate analysis of freedom from distant metastases revealed that locoregional control (F=29. 332,P<0. 01) significantly influenced this end point. Conclusion: Sali-vary gland carcinoma could achieve high local control rate after being treated by surgery combined with 125 I internal brachytherapy, and the average interval from diagnosis to DM was prolonged, DM was signifi-cantly influenced bylocoregional control.

Objective To explore the method of target volume determination of postoperative 125I seeds interstitial brachytherapy in parotid gland carcinoma.Methods A total of 31 cases( 14 males and 17 famales) with primary parotid carcinoma who were treated in Peking University Hospital of Stomatology from Oct 2002 to Nov 2006.The patients' average age was 38.2 years.All patients underwent tumor resection and postoperative 125I seeds interstitial brachytherapy with 60 Gy matched peripheral dose.The spiral CT was performed for treatment plan and quality verification before and after the brachytherapy.The bone and muscle landmarks surrounding parotid were selected as reference for target volume determination.D90 of target volume and dose of organs at risk were calculated,while the target volume and D90 of target volume of verification were compared with that of treatment plan through quality verification.Results The target volume or D90 of target volume before and after treatment was not statistically different.D90 of target volume was more than 60 Gy.During 3 -7 years of follow-up,all patients had no recurrence.ConclusionsAccording to the follow-up results,the method used for target volume determination in this paper might be satisfied.