Preliminary Study on the Relationship of BRAF Mutations with the Outcome of the First 131I Radiotherapy and Malignant Biological Characteristics in Papillary Thyroid Carcinoma.

OBJECTIVE: To investigate the relationship of BRAF mutation with the outcome of the first postoperative 131I treatment and malignant biological characteristics in papillary thyroid carcinoma (PTC). METHODS: Thirty-three patients with PTC who underwent their first 131I treatment after total thyroidectomy were enrolled in this study. BRAF mutation in postoperative tumor tissue and circulating tumor DNA (ctDNA) in peripheral blood at the time of 131I treatment were detected. According to the status of BRAF mutation, all patients were divided into 2 groups in each category of tumor tissues and ctDNA, respectively: 1) BRAF mutation, 2) BRAF wild-type. The Fisher's exact test was performed to analyze the relationship of BRAF mutation in either tumor tissue or ctDNA with the outcome of the first 131I treatment and malignant characteristics of PTC. RESULTS: BRAF mutation was detected in tumor tissues in 25 patients (25/33,75.8%), and all the patients had single mutation site. In ctDNA, BRAF mutation was detected in 5 patients (5/33, 15.2%), and all the patients had single mutation site. In both tumor tissues and ctDNA, BRAF mutation showed no relationship with the outcome of first 131I treatment and the malignant biological characteristics (P>0.05). CONCLUSION: The value of BRAF mutation alone might be limited in predicting therapeutic outcome of the first 131I treatment in PTC. No definitive relevance was found between BRAF mutation and malignant biological features in PTC.

Compact optically pumped cesium beam atomic clock with a 5-day frequency stability of 7×10-15.

Compared to other commercial atomic clocks in the time keeping field, the greatest advantage of cesium beam atomic clocks is their superior long-term stability. Compared to magnetic state-selection clocks, optically pumped cesium beam atomic clocks have more interacting atoms, which results in better stability potential. To achieve good long-term stability, we propose methods including stabilization of laser power and reconstruction of circuits. They play a key role in the long-term stability of cesium beam atomic clocks. After 75 days of continuous running and measurement, we released the 5-day stability results (7×10-15 Allan deviation) of our optically pumped cesium beam atomic clock. To the best of our knowledge, this is the best 5-day stability result ever reported for compact optically pumped cesium beam atomic clocks.

A linewidth locking method to control the microwave power in optically pumped cesium-beam clocks.

In this paper, we present a linewidth locking method to control the microwave power in optically pumped cesium-beam frequency standards. The responses of optically pumped cesium-beam tubes and classical cesium-beam tubes are analyzed and compared against the power of the microwave field. Due to the wide probability distribution of atomic velocity resulting from the optical state preparation and detection, the linewidth of the Ramsey pattern is sensitive to the microwave power. The results can be used to control the microwave power instead of using the traditional extremum method. The advantages of the new method are discussed, and we named this new method the linewidth locking method. When the microwave power is well controlled at a low level by the linewidth locking method, the frequency stability of cesium-beam clocks will be improved to a certain degree for the reduction of the Ramsey pattern linewidth. In experiment, using the linewidth locking method, the Allan deviation of our optically pumped cesium-beam frequency standard is 2.64×10-12/τ and continues until the averaging time exceeds 1 × 105 s, which is 17% better than that using the traditional extremum method.

Frequency instability of a miniature optically pumped cesium-beam atomic frequency standard.

This paper proposes a miniature optically pumped cesium-beam atomic frequency standard with a volume of 38.4 l and a weight of 28 kg and examines the main factors that affect its signal-to-noise ratio (SNR). Methods to improve the SNR are proposed, which improve the short-term frequency instability: installing a collimator at the exit of the cesium oven, using the beam fluorescence spectrum with the fiber-coupled output to stabilize the laser frequency, and using the 4-5 cycling transition of the cesium D2 line for the atomic detection. We also examine several frequency shifts that affect the long-term frequency instability and detail methods to reduce these shifts. At present, the frequency instability achieved by the Peking University miniature optically pumped cesium-beam frequency standard has reached 3.12×10-12/τ.

Impact factors for the outcome of the first 131I radiotherapy in patients with papillary thyroid carcinoma after total thyroidectomy.

OBJECTIVE: To investigate the impact factors of the outcome of the first 131I treatment in patients with papillary thyroid carcinoma (PTC) after total thyroidectomy. METHODS: Three hundred and fifty-three patients [256 females, 97 males, average age (43.58 ± 12.33 years)] with PTC after total thyroidectomy who underwent 131I treatment from July 2014 to August 2017 were retrospectively analyzed. Curative efficacy of 131I treatment was assessed 6 months afterward. Therapeutic outcome was determined according to thyrotropin (TSH)-stimulated thyroglobulin (sTg) level, 131I diagnostic whole-body scan (Dx-WBS) after 131I treatment and other imaging modalities. Twelve possible factors affecting the therapeutic outcome of 131I treatment including patients' gender, age, interval between surgery and 131I treatment, primary tumor size and extrathyroidal extension (ETE), number and range of primary tumor lesions, result of 99mTcO4- thyroid scan, number of metastatic lymph nodes (LN), pre-treatment laboratory measurements [TSH, sTg and Tg antibody (TgAb)], therapeutic dose of 131I and result of 131I post-treatment whole-body scan (Rx-WBS) were analyzed using univariate and multivariate logistic regression. The receiver operator characteristic (ROC) curve and diagnostic cutoff value were analyzed to evaluate the predictive value of the significant quantitative impact factors for the outcome of 131I treatment. RESULTS: The curative rate of the first 131I treatment in patients with PTC after total thyroidectomy was 62.32% (220/353). Univariate analysis indicated that gender, age, number and range of primary tumor lesions, number of metastatic LN, pre-treatment sTg and TgAb, therapeutic dose of 131I and result of 131I Rx-WBS (all P < 0.05) were significant factors affecting the outcome of 131I treatment. Multivariate analysis revealed that the numbers of metastatic LN (regression coefficient = 1.170) and sTg (regression coefficient = 0.280) were significant impact factors (all P < 0.001). The regression equation was: Logit P = - 3.997 + 1.170 × number of metastatic LN + 0.280 × sTg (χ2 = 210.68, P < 0.001). Taking sTg as a predictive factor for the outcome of the first 131I treatment, the area under the curve (AUC) of ROC for sTg was 0.917 (95% CI 0.890-0.944). The cutoff value of sTg was 2.69 ng/mL with a sensitivity of 92.48% (123/133) and specificity of 74.09% (163/220). CONCLUSION: Patients with PTC after total thyroidectomy with low pre-treatment sTg level and few lymph node metastases are more likely to be cured by the first 131I treatment.

Experimental study on the therapeutic effect of positron emission tomography agent [¹8F]-labeled 2-deoxy-2-fluoro-d-glucose in a colon cancer mouse model.

The purpose of this study was to assess the therapeutic effect of positron emission tomography agent [¹8F]-labeled 2-deoxy-2-fluoro-d-glucose (¹8F-FDG) in a colorectal cancer mouse model. Three (3) tumor-bearing mice groups were treated with different doses of ¹8F-FDG. Mice were imaged by positron emission tomography with ¹8F-FDG before and after treatment weekly and the tumor growth rate was calculated. Tumor, brain, heart, and kidney of mice were analyzed for expression of glucose transporters and vascular endothelial growth factor (VEGF) by immunofluorescent staining, and the presence of apoptosis was detected by terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) method. All 3 treated groups showed significant ¹8F-FDG reduction compared with the control group (p < 0.05). With higher treatment dose, better treatment response was observed. The tumor growth rate of all 3 treated groups was also significantly decreased after treatment (p < 0.05). Immunohistochemistry showed that tumors expressed more glucose transporters than in brain, heart, and kidney. The ¹8F-FDG treatment of mice resulted in apoptotic cell death in all 3 treated groups, which showed significant higher apoptotic cells than the control group (p < 0.05). The study suggests that ¹8F-FDG has a therapeutic effect in colonic cancer animal model, which indicates the potential for the development of positron therapy for colonic cancer and other cancers.

11C-NMSP/ 18F-FDG microPET to monitor neural stem cell transplantation in a rat model of traumatic brain injury.

PURPOSE: To investigate whether (11)C-N-methylspiperone ((11)C-NMSP) microPET could be used for imaging neural stem cells (NSCs) transplantation in a rat model of traumatic brain injury. METHODS: NSCs were induced to express dopamine receptor type 2 (DRD(2)), then confirmed by RT-PCR, Western blotting and immunocytochemistry. Eighteen rats were subjected to focal traumatic brain injury in the right parietal lobe and then assigned randomly to the transplantation group and the control group. NSCs labeled with 5-bromo-2-deoxyuridine (BrdU) were transplanted into the cerebral lesion of the transplantation group. MicroPET scan using (11)C-NMSP and (18)F-FDG were performed to detect the DRD(2) expression of transplanted NSCs and the regional glucose metabolism in the cerebral lesion, respectively. Behavioral neurological function of rats were also tested. RESULTS: Histological analysis identified viable NSCs. Western blotting and immunofluorescence showed high level of NSCs-induced DRD(2) expression. Immunostaining demonstrated high levels of survived BrdU+ and DRD(2)+ donor cells in the cerebral lesion 2 weeks after transplantation. The lesion-to-normal contralateral ratio (L/N ratio) of (11)C-NMSP in the cerebral lesion decreased significantly from 97% to 68% after injury and increased dramatically to 137% 1 day after the transplantation and then decreased gradually. Glucose metabolism showed a decrease of 35% in the cerebral lesion 1 day after injury and recovered to 87% 2 weeks after transplantation. The behavioral neurological function of the transplantation group was significantly improved compared with the control group. CONCLUSIONS: This study verified that (11)C-NMSP microPET can be used to assess the NSCs-induced DRD(2) expression in rat model.