Catalytic metal-nucleotide coordinative cytoskeleton on algae cell towards photosynthetic hydrogen production under air.

A metal-nucleotide coordinative cytoskeleton with ascorbate oxidase-like catalytic behavior was constructed on an individual algae cell wall, which endows the engineered cells with the capability of self-generating a localized hypoxic microenvironment around the cell surface, and thus allows the functionality switching from photosynthetic oxygen production to efficient hydrogen evolution for over one month.

Titanium Surfaces Modified with Graphene Oxide/Gelatin Composite Coatings for Enhanced Antibacterial Properties and Biological Activities.

Titanium alloys have been widely used in orthopedic implants due to their excellent physicochemical properties and good biocompatibility. However, in practice, titanium implants may fail to integrate or develop an implant-centered infection. Because of its excellent mechanical properties, bone integrability, biocompatibility, antibacterial properties, and so on, graphene oxide is increasingly being used in the preparation of composite biomaterials. The percutaneous titanium implants are used as the research object in this project. To solve the integration of implant and tissue, a graphene oxide/gelatin (GO/gel) composite coating was used to optimize the implant surface. Bacterial and cell experiments were used to investigate the antimicrobial activity, biocompatibility, and regulation of macrophage polarization of GO/gel-modified titanium. According to our findings, GO/gel-modified titanium has a good bacteriostatic effect against Staphylococcus aureus. On the modified surface, L929 cells proliferated well and showed no cytotoxicity. Simultaneously, the GO/gel-modified titanium surface could inhibit macrophage adhesion and spread in the early stage of culture and showed a more obvious inflammatory decline in the late stage of culture. These findings implied that GO/gel-modified titanium is advantageous for resistant bacteria and tissue remolding.

Free-Radical Cascade Generated by AIPH/Fe3O4-Coloaded Nanoparticles Enhances MRI-Guided Chemo/Thermodynamic Hypoxic Tumor Therapy.

Free radicals, including reactive oxygen species (ROS), play a critical role in determining cell's fate. When the level of free radicals is increased to a fatal value, it causes cancer cells to undergo senescence or cell death. Strategies that target this mechanism offer promising therapies against cancer. However, efficient and sustainable systems that generate free radicals, especially oxygen-independent systems, remain deficient. Herein, functionalized PLGA-based nanocomposites that efficiently co-deliver magnetic nanoparticles and 2,2'-azobis[2-(2-imidazolin-2-yl) propane]-dihydrochloride (AIPH) were fabricated to achieve photothermal-induced thermodynamic therapy combined with macrophage polarization strategies; this therapy targets hypoxic tumors through the generation of an oxygen-independent free-radical cascade. These hybrid NPs can accumulate in the tumor microenvironment, and the encapsulated MNPs not only serve as contrast agents for enhanced magnetic resonance imaging but also exhibit the expected photothermal conversion and trigger the decomposition of AIPH to generate free radicals, thus causing cancer cell death. More importantly, the cell debris from apoptotic or necrotic cancer cells carries nondegraded MNPs, which can be endocytosed by recruited TAMs. MNPs can further induce TAMs to polarize to the M1 subtype to subsequently generate ROS. This study provides an alternative method for the generation of an oxygen-independent free-radical cascade for tumor co-therapy guided by magnetic resonance imaging PTT/TDT.

Prognostic evaluation model for papillary thyroid cancer: a retrospective study of 660 cases.

BACKGROUND: Prognostic evaluation model for papillary thyroid cancer is very important for guiding the personalized treatment and follow-up strategy. There are imperfections in the system existed, and there is no suitable prognostic model for Chinese population. METHODS: This study was based on the clinic and follow-up data of 660 patients received surgical treatments in the Department of Head and Neck Surgery, Fudan University Shanghai Cancer Center from 2000 to 2005. Cox univariate/multivariate analysis was used to explore the influence factors of prognosis, and nomogram model was performed to establish a prognostic prediction system. RESULTS: Totally, 660 patients for initial treatment were included in our analysis with a median follow-up of 113.5 months. Five-, 10- and 15-year disease-free survival rate was 95.5%, 90.2% and 89.2%. Five-, 10- and 15-year overall survival rate was 99.7%, 99.2% and 99.1%. Residual tumor was associated with overall survival [hazard ratio (HR) 20.9, 95% confidence interval (CI): 2.3-187.6, P<0.05]. Age of onset (HR 2.00, 95% CI: 1.17-3.42, P<0.05) and the dimension of lymph nodes involved (0.2-3 cm: HR 3.67, 95% CI: 1.13-11.87, P<0.05; >3 cm: HR 5.20, 95% CI: 1.31-20.65, P<0.05) were independent influence factors of disease-free survival. The nomogram model for predicting prognosis of papillary thyroid cancer was established with a moderate predictive value (c-index 0.71, 95% CI: 0.57-0.84). CONCLUSIONS: The prognosis of papillary thyroid cancer is very good after appropriate treatment. Age and the dimension of lymph nodes involved were independent influence factors of disease-free survival for papillary thyroid cancer. A prognostic prediction model for Chinese population was established with moderate predictive value. A study with larger samples and including more factors of prognosis is necessary to increase the predictive value of model.

Emodin inhibits the proliferation of papillary thyroid carcinoma by activating AMPK.

Emodin has been demonstrated to serve antitumor roles in a variety of tumor types, but the effect of emodin on papillary thyroid carcinoma and its molecular mechanisms remain unclear. In the current study, the role of emodin on papillary thyroid carcinoma was analyzed in vitro and in vivo. TPC-1 cells were treated with emodin (0, 10, 25 or 50 µM), and cell viability and apoptosis were detected using Cell Counting Kit-8 and flow cytometry, respectively. The expression levels of AMPK-associated proteins were examined using western blot analysis. To study the effect of emodin on the AMPK pathway, AMPK activator, AICAR and an AMPK inhibitor, Dorsomorphin, were used in TPC-1 cells. In vivo, mice were used to confirm the mechanism of emodin on papillary thyroid carcinoma. The results of the current study indicated that emodin treatment induced cell apoptosis and cell cycle arrest in TPC-1 cells. Furthermore, the inhibitory effect increased in a dose dependent manner. Following emodin treatment, the cell viability of TPC-1 cells was significantly decreased, and apoptosis rate increased (P<0.05). Furthermore, the expression levels of AMPK were increased in the emodin group compared with the control group (P<0.05). Similar effects were observed following AMPK activator treatment in TPC-1 cells. Following AMPK activator treatment, cell proliferation and the cell cycle were inhibited. Also, the AMPK inhibitor was demonstrated to mediate the therapeutic effect of emodin. In addition, the results of the present study demonstrated that emodin inhibited the MEK/ERK pathway. Additionally, the in vivo results of the current study were consistent with those in vitro. In conclusion, the current study demonstrated that the administration of Emodin inhibited the proliferation of papillary thyroid cancer cells via activating AMPK pathway activity.

Increased thyroid malignancy in patients with primary hyperparathyroidism.

BACKGROUND: Multiple studies have reported the increased incidence of thyroid cancer in patients with primary hyperparathyroidism (PHPT). However, the underlying risk factors of concomitant thyroid cancer in patients with PHPT remain unknown. The primary aim of this study was to examine the records of patients with PHPT to identify characteristics that correlated with the presence of coexisting thyroid nodules, and which may have an implication for the prediction of thyroid cancer. METHODS: Medical records of consecutive patients with PHPT (n = 318) were reviewed from January 2010 to September 2020 in two tertiary medical centers in China. Patient clinicopathological and biological data were collected and analyzed. RESULTS: Of a total of 318 patients with PHPT, 105 (33.0%) patients had thyroid nodules and 26 (8.2%) patients were concomitant with thyroid cancer. A total of 38 thyroid nodules taken from 26 patients were pathologically assessed to be well-differentiated papillary thyroid carcinoma (PTC), with 81% being papillary thyroid microcarcinoma (PTMC). In 79% (30/38) of these cancers, thyroid nodules were considered suspicious following preoperative ultrasound. Multinomial logistic regression analysis revealed that female gender was associated with increased risk of thyroid nodules (OR = 2.13, 95% CI: 1.13-3.99, P = 0.019), while lower log-transformed parathyroid hormone levels were an independent predictor of thyroid cancer in patients with PHPT (OR = 0.50, 95% CI: 0.26-0.93, P = 0.028). CONCLUSION: In conclusion, we observed a relatively high prevalence of thyroid cancer in our cohort of Chinese patients with PHPT. Evaluation of thyroid nodules by preoperative ultrasound may be advisable in patients with PHPT, particularly for females and patients with modestly elevated serum parathyroid hormone levels.

Inhibition of Rac1 reverses enzalutamide resistance in castration-resistant prostate cancer.

Enzalutamide, an androgen receptor inhibitor, has been clinically approved for the treatment of metastatic castration-resistant prostate cancer (CRPC) in the United States. However, patients only benefit from enzalutamide for a short period of time as resistance may develop. Therefore, it is vital to develop a novel strategy to overcome enzalutamide resistance. Ras-related C3 botulinum toxin substrate 1 (Rac1), which is commonly upregulated in human cancer types, has been recognized as a key molecular component in tumorigenesis, invasion and metastasis. However, the role of Rac1 in enzalutamide-resistance in prostate cancer (PCa) remains unknown. In the present study, Rac1 was demonstrated to be upregulated in enzalutamide-resistant PCa cells, and Rac1 knockdown inhibited enzalutamide-resistant cell proliferation and colony formation. Western blotting results indicated that enzalutamide treatment downregulated the expression levels of JNK and activated transcription factor 2, as well as enhanced the Bax/Bcl-2 ratio and induced cleavage of poly-ADP ribose polymerase. Moreover, knockdown of Rac1 in MR49F cells significantly inhibited cell migration and invasion via the downregulation of Snail and the upregulation of E-cadherin. The results of a nude mouse xenograft tumor model using 22RV1 cells demonstrated that enzalutamide inhibited tumor growth after Rac1 knockdown dramatically, compared to vehicle and single treatment groups. Therefore, the present study provided novel evidence that Rac1 may serve a crucial role in enzalutamide resistance, and that targeting Rac1 may be a potential approach for the treatment of CRPC.

Neuroprotective Effects of Lindleyin on Hydrogen Peroxide-Induced Cell Injury and MPTP-Induced Parkinson's Disease in C57BL/6 Mice.

Oxidative stress (OS) is a crucial factor influencing the development of Parkinson's disease (PD). Here we first reported that Lindleyin (Lin), one of the major components of rhubarb, possessed neuroprotective effects against H2O2-induced SH-SY5Y cell injury and MPTP-induced PD of C57BL/6 mice. The results showed that Lin can decrease cell death and apoptotic rate induced by H2O2 through inhibiting mitochondrial apoptotic pathway and increasing the activities of SOD, GSH-Px, and CAT as well as decreasing the level of MDA. In addition, in vivo studies showed that oral administration of Lin (5 or 20 mg/kg) showed significant change in motor function deficits, antioxidant enzyme activities, apoptotic pathway, and tyrosine hydroxylase expression. Our results reveal that Lin might be a promising anti-PD agent by reducing OS and apoptosis.

Automated radiosynthesis and preclinical evaluation of Al[18F]F-NOTA-P-GnRH for PET imaging of GnRH receptor-positive tumors.

INTRODUCTION: Gonadotropin releasing hormone (GnRH) receptor is overexpressed in many human tumors. Previously we developed a 18F-labelled GnRH peptide. Although the GnRH-targeted PET probe can be clearly visualized by microPET imaging in a PC-3 xenograft model, clinical applications of the probe have been limited by complex labeling procedures, poor radiochemical yield, and unwanted accumulation in GnRH receptor negative tissues. In this study, we have designed a new 18F-labelled GnRH peptide that is more amenable to clinical development. METHODS: GnRH peptide analogues NOTA-P-GnRH was synthesized and automated radiolabeled with 18F using a Al[18F]F complex on a modified PET-MF-2V-IT-I synthesis module. The GnRH receptor affinities of AlF-NOTA-P-GnRH and NOTA-P-GnRH were determined by in vitro competitive binding assay. For in vitro characterization determination of stability and partition coefficients were carried out, respectively. Dynamic microPET and biodistribution studies of Al[18F]F-NOTA-P-GnRH were evaluated in xenograft tumor mouse models. RESULTS: The total radiochemical synthesis and purification of Al[18F]F-NOTA-P-GnRH was completed within 35 min with a decay-corrected yield of 35 ± 10%. The logP value of Al[18F]F-NOTA-P-GnRH was -2.74 ± 0.04 and the tracer was stable in phosphate-buffered saline, and bovine and human serum. The IC50 values of AlF-NOTA-P-GnRH and NOTA-P-GnRH were 116 nM and 56.2 nM, respectively. Dynamic PET imaging together with ex vivo biodistribution analyses revealed that Al[18F]F-NOTA-P-GnRH was clearly delineated in both PC-3 and MDA-MB-231 xenografted tumors. CONCLUSION: Al[18F]F-NOTA-P-GnRH can be efficiently produced on a commercially available automated synthesis module and has potential for use in clinical diagnosis of GnRH receptor-positive tumors. ADVANCES IN KNOWLEDGE: Our studies developed the automated radiosynthesis of a new 18F-labelled GnRH tracer and preclinical evaluation for future clinical application. IMPLICATIONS FOR PATIENT CARE: Quantitative and noninvasive imaging of GnRH expression would provide information for diagnosis and treatment of cancer patients.

1,25-Dihydroxy vitamin D3 inhibits the Ras-MEK-ERK pathway and regulates proliferation and apoptosis of papillary thyroid carcinoma.

OBJECTIVE: To explore the effects of 1,25-dihydroxy vitamin D3 [1,25-(OH)2D3] on the proliferation and apoptosis of papillary thyroid carcinoma and to investigate its possible mechanism. MATERIALS AND METHODS: The papillary thyroid carcinoma cell line TPC-1 was cultured, and the cells were divided into control group, the 1,25-(OH)2D3 group, and the 1,25-(OH)2D3 + ML-098 (Ras agonist) group. Cell proliferation was observed by MTT. The colony formation viability of cells was detected by the plate cloning assay. Cell migration was observed by the scratch assay. Apoptosis was detected by flow cytometry. The expression of Ki67 and Caspase-3, and the activity of Ras-MEK-ERK pathway were detected by western blot. RESULTS: Compared with the Control group, the proliferation, colony formation and migration ability of cells in the drug group were significantly decreased. The number of apoptotic cells was significantly increased, the expression of Ki67 protein was decreased, and the expression of Caspase-3 protein was upregulated. The phosphorylation levels of Ras, p-ERK1/2, and p-MEK were decreased. Compared with the drug group, the cloning and migration biological activity of cells in the 1,25-(OH)2D3 + ML-098 group was significantly enhanced (p < 0.05). The number of apoptotic cells was decreased, while the Ki67 protein level was increased. In addition, the Caspase-3 protein level was decreased, and the Ras-MEK-ERK level was also enhanced. Furthermore, the antitumor activity of 1,25-(OH)2D3 was reversed by the Ras agonist ML-098. CONCLUSION: 1,25-(OH)2D3 can inhibit the activity and promote apoptosis of the papillary thyroid carcinoma cell line TPC-1, and its mechanism may be related to the inhibition of the Ras-MEK-ERK pathway activity, thus affecting the proliferation and expression of apoptosis-related proteins.

Molecular characterization and transcription analysis of DNA methyltransferase genes in tomato (Solanum lycopersicum).

DNA methylation plays an important role in plant growth and development, gene expression regulation, and maintenance of genome stability. However, only little information regarding stress-related DNA methyltransferases (MTases) genes is available in tomato. Here, we report the analysis of nine tomato MTases, which were categorized into four known subfamilies. Structural analysis suggested their DNA methylase domains are highly conserved, whereas the N-terminals are divergent. Tissue-specific analysis of these MTase genes revealed that SlCMT2, SlCMT3, and SlDRM5 were expressed higher in young leaves, while SlMET1, SlCMT4, SlDRM7, and SlDRM8 were highly expressed in immature green fruit, and their expression declined continuously with further fruit development. In contrast, SlMETL was highly expressed in ripening fruit and displayed an up-regulated tendency during fruit development. In addition, the expression of SlMET1 in the ripening of mutant rin and Nr tomatoes is significantly higher compared to wild-type tomato, suggesting that SlMET1 was negatively regulated by the ethylene signal and ripening regulator MADS-RIN. Furthermore, expression analysis under abiotic stresses revealed that these MTase genes were stress-responsive and may function diversely in different stress conditions. Overall, our results provide valuable information for exploring the regulation of tomato fruit ripening and response to abiotic stress through DNA methylation.

Pancreatic stem cells differentiate into insulin-secreting cells on fibroblast-modified PLGA membranes.

Diabetes mellitus is an epidemic worldwide. Pancreatic stem cells can be induced to differentiate into insulin-secreting cells, this method is an effective way to solve the shortage of islet donor. Poly (lactic acid-co-glycolic acid (PLGA) copolymer is an excellent scaffold for tissue engineering as it presents good biocompatibility and film forming properties. In this study, we adopted biological methods, using fibroblast-coated PLGA diaphragm to form a biological membrane, and then pancreatic stem cells were cultured on the fibroblast-modified PLGA membrane and the two-step induction method was utilized to induce the differentiation of pancreatic stem cells into insulin-secreting cells. The proliferation and differentiation of pancreatic stem cells on the fibroblast-modified PLGA membrane as well as the expression of genes related to the differentiation of pancreatic stem cells were examined in both normal and induced cultures to explore the potential of fibroblast-modified PLGA membrane for the transplantation to treat diabetes mellitus. The results indicated that fibroblasts can effectively improve the cell compatibility and histocompatibility of the PLGA membrane and promote the proliferation and differentiation of pancreatic stem cells. After induction, real-time fluorescence quantitative PCR (FQRT-PCR) results showed there were more Notch receptors and its ligands expressed in the membranes of pancreatic stem cells than non-induced pancreatic stem cells or fibroblast. Semiconductor quantum dot coupled-anti-complex probe experiments revealed that induced pancreatic stem cells had higher expression levels of Notch 2 and Delta-like 1 than non-induced ones, which may regulate the expression of Neurogenin-3 (Ngn3) and Hairy/Enhancer of split-1 gene (Hes1) through Notch signaling interaction between fibroblasts and pancreatic stem cells as well as enhance the proliferation of pancreatic stem cells and their differentiation into insulin-secreting cells. Further, our study suggests that the fibroblast-modified PLGA membrane can be used as matrix material composed of pancreatic stem cells or other stem cells to construct artificial islet tissue for the treatment of diabetes mellitus.

Cornin protects SH­SY5Y cells against oxygen and glucose deprivation­induced autophagy through the PI3K/Akt/mTOR pathway.

It has been reported that cornin may reduce neuronal death during cerebral ischemia; however, little is known about the molecular mechanism of the role of corninin autophagy in SH­SY5Y neuronal cells. In the present study, oxygen­glucose deprivation (OGD)­treated cells were used as a cerebral ischemia model in vitro. The results demonstrated that cornin was able to reduce neuronal cell loss, increase the apoptosis regulator Bcl­2/apoptosis regulator BAX ratio, and decrease the protein levels of caspase­3. In addition, cornin decreased the microtubule­associated proteins 1A/1B light chain 3B (LC3)­II/LC3­I ratio and beclin­1 protein expression, and resulted in an upregulation in phosphorylated (p)­RAC­α serine/threonine­protein kinase (Akt), p­protein kinase mTOR (mTOR) in OGD­treated SH­SY5Y cells. Additionally, it was observed that following inhibition of PI3K/Akt by LY294002, the levels of p­Akt and p­mTOR were markedly decreased, and the LC3­II/LC3­I ratio and beclin­1 were increased. Similarly, following inhibition of mTOR by rapamycin, LC3­II/LC3­I and Beclin­1 were significantly increased in SH­SY5Y cells. These results indicated that cornin protected SH­SY5Y cells against OGD­induced autophagy through the PI3K/Akt/mTOR pathway.

Construction of functional pancreatic artificial islet tissue composed of fibroblast-modified polylactic- co-glycolic acid membrane and pancreatic stem cells.

Objective To improve the biocompatibility between polylactic- co-glycolic acid membrane and pancreatic stem cells, rat fibroblasts were used to modify the polylactic- co-glycolic acid membrane. Meanwhile, we constructed artificial islet tissue by compound culturing the pancreatic stem cells and the fibroblast-modified polylactic- co-glycolic acid membrane and explored the function of artificial islets in diabetic nude mice. Methods Pancreatic stem cells were cultured on the fibroblast-modified polylactic- co-glycolic acid membrane in dulbecco's modified eagle medium containing activin-A, ß-catenin, and exendin-4. The differentiated pancreatic stem cells combined with modified polylactic- co-glycolic acid membrane were implanted subcutaneously in diabetic nude mice. The function of artificial islet tissue was explored by detecting blood levels of glucose and insulin in diabetic nude mice. Moreover, the proliferation and differentiation of pancreatic stem cells on modified polylactic- co-glycolic acid membrane as well as the changes on the tissue structure of artificial islets were investigated by immunofluorescence and haematoxylin and eosin staining. Results The pancreatic stem cells differentiated into islet-like cells and secreted insulin when cultured on fibroblast-modified polylactic- co-glycolic acid membrane. Furthermore, when the artificial islet tissues were implanted into diabetic nude mice, the pancreatic stem cells combined with polylactic- co-glycolic acid membrane modified by fibroblasts proliferated, differentiated, and secreted insulin to reduce blood glucose levels in diabetic nude mice. Conclusion Pancreatic stem cells can be induced to differentiate into islet-like cells in vitro. In vivo, the artificial islet tissue can effectively regulate the blood glucose level in nude mice within a short period. However, as time increased, the structure of the artificial islets was destroyed due to the erosion of blood cells that resulted in the gradual loss of artificial islet function.

Thalidomide-based Regimens for Elderly and/or Transplant Ineligible Patients with Multiple Myeloma: A Meta-analysis.

BACKGROUND: Thalidomide is an immunomodulatory and anti-angiogenic drug that has shown promise in patients with myeloma. Trials comparing efficacy of standard melphalan and prednisone (MP) therapy with MP plus thalidomide (MPT) in transplant-ineligible or elderly patients with multiple myeloma (MM) have provided conflicting evidence. This meta-analysis aimed to determine the efficacy and toxicity of thalidomide in previously untreated elderly patients with myeloma. METHODS: Medline, the Cochrane Controlled Trials register, conference proceedings of the American Society of Hematology (1995-2014), the American Society of Clinical Oncology (1995-2014), and CBM, VIP, and CNKI databases were searched for randomized control trials with the use of the medical subject headings "MM " and "thalidomide ". Trials were assessed by two reviewers for eligibility. Meta-analysis was conducted using a fixed effects model. Sensitivity analysis was performed to test the robustness of the findings. RESULTS: Overall, seven trials were identified, covering a total of 1821 subjects. The summary hazard ratio (thalidomide vs. control) was 0.82 (95% confidence interval [CI]: 0.72-0.94) for overall survival (OS), and 0.65 (95% CI: 0.58-0.73) for progression-free survival, in favor of thalidomide treated group. The risk ratio of complete response with induction thalidomide was 3.48 (95% CI: 2.24-5.41). A higher rate of III/IV adverse events were observed in MPT arm compared with the MP arm. However, analysis of sub-groups administering anticoagulation as venous thromboembolism prophylaxis suggested no difference in relative risk of thrombotic events between two arms (RR = 1.47, 95% CI: 0.43-5.07, P = 0.54). Further analysis of trials on the treatment effects of MPT versus MP on adverse events-related mortality showed no statistical difference between two arms (RR = 1.24, 95% CI: [0.95-1.63], P = 0.120). CONCLUSION: Thalidomide appears to improve the OS of elderly and/or transplant-ineligible patients with MM when it is added to standard MP therapy.

BRAF-Activated Long Noncoding RNA Modulates Papillary Thyroid Carcinoma Cell Proliferation through Regulating Thyroid Stimulating Hormone Receptor.

PURPOSE: The importance of long noncoding RNAs (lncRNAs) in tumorigenesis has recently been demonstrated. However, the role of lncRNAs in development of thyroid cancer remains largely unknown. MATERIALS AND METHODS: Using quantitative reverse transcription polymerase chain reaction, expression of three lncRNAs, including BRAF-activated long noncoding RNA (BANCR), papillary thyroid cancer susceptibility candidate 3 (PTCSC3), and noncoding RNA associated with mitogen-activated protein kinase pathway and growth arrest (NAMA), was investigated in the current study. RESULTS: Of the three lncRNAs (BANCR, PTCSC3, and NAMA), expression of BANCR was significantly up-regulated while PTCSC3 and NAMA were significantly down-regulated in papillary thyroid carcinoma (PTC) compared to that in normal tissue. BANCR-knockdown in a PTC-derived cell line (IHH-4) resulted in significant suppression of thyroid stimulating hormone receptor (TSHR). BANCR-knockdown also led to inhibition of cell growth and cell cycle arrest at G0/G1 phase through down-regulation of cyclin D1. In addition, BANCR was enriched by polycomb enhancer of zeste homolog 2 (EZH2), and silencing BANCR led to decreased chromatin recruitment of EZH2, which resulted significantly reduced expression of TSHR. CONCLUSION: These findings indicate that BANCR may contribute to the tumorigenesis of PTC through regulation of cyclin D1 and TSHR.

Application experience of intraoperative neuromonitoring in thyroidectomy.

OBJECTIVE: The aim of this study is to summarize the experience of intraoperative neuromonitoring system for monitoring and protection of recurrent laryngeal nerve during thyroid surgery. METHODS: There were 220 cases in this study, male 53, female 167, mean age 38.2 years old. 85 cases in the study had thyroid cancer, 19 cases had thyroid benign tumor, 90 cases had thyroid goiter, 3 cases had Hashimoto's diseases, and 23 cases had hyperthyroidism. The tumor diameters were over than 5 cm in 113 cases. In the procedure, two recording needle electrodes were put into cricothyroid muscle; one stimulator electrodes was explored in tracheo-asophageal groove, if recurrent laryngeal nerves were right there or near, doctors could see the electromyogram and hear the toot honk. With careful dissection, recurrent laryngeal nerve could be found out till explored into the larynx site. RESULTS: 207 cases (278 sizes) of 220 were finished, electromyogram was not drawn out in 13 cases; 9 cases were false-negative because of system and anesthesia questions; needle electrodes cannot be put in properly in 4 cases because of cricothyroid muscle cancer invasion. No permanent recurrent laryngeal nerve paralysis occurred, 2 cases with transient nerve paralysis recovered in one month. CONCLUSION: The intraoperative neuromonitoring system can avoid damage of the recurrent laryngeal nerves when exposing the recurrent laryngeal nerve in the whole operation, therefore, with less medical complications.

F-18 FDG in conjunction with 11C-choline PET/CT in the diagnosis of hepatocellular carcinoma.

PURPOSE: F-18 fluorodeoxyglucose (F-18 FDG) positron emission tomography (PET)/computed tomography (CT) alone has limited sensitivity for the diagnosis of hepatocellular carcinoma (HCC). We hoped to improve the diagnostic sensitivity by combining F-18 FDG and C-choline PET/CT. MATERIALS AND METHODS: A total of 76 consecutive patients with HCC were prospectively enrolled. Whole-body F-18 FDG PET/CT scan was performed for all patients. In those patients with negative F-18 FDG scans, a regional C-choline PET/CT scan was also performed. RESULTS: Positive F-18 FDG scans were noted in 61.1% (48/76) patients with HCC. Increased F-18 FDG uptake correlated with decreased tumor differentiation (P = 0.042). In 28 HCC patients with negative F-18 FDG scans, C-choline scan was positive in 71.4% patients. C-choline scan did not detect any significant difference between well- and moderately differentiated HCC (P = 0.585). Compared with F-18 FDG scan, C-choline scan showed a trend toward an improved detection of well-differentiated HCC (66.7% vs. 35.7%, NS). For detection of moderately differentiated HCC, the sensitivity of C-choline and F-18 FDG PET/CT was similar (85.7% vs. 72.0%, P = 0.648). The dual-tracer modality improved the diagnostic sensitivity of F-18 FDG PET/CT alone from 63.1% to 89.5% (P < 0.001). CONCLUSIONS: F-18 FDG in conjunction with C-choline increases the sensitivity of PET/CT in detecting HCC.

A facile and rapid automated synthesis of 3'-deoxy-3'-[(18)F]fluorothymidine.

AIM: To develop a simplified and fully automated synthesis procedure of 3'-deoxy-3'-[(18)F]fluorothymidine ([(18)F]FLT) using PET-MF-2V-IT-I synthesis module. METHODS: Synthesis of [(18)F]FLT was performed using PET-MF-2V-IT-I synthesis module by one-pot two-step reaction procedure, including nucleophilic fluorination of 3-N-t-butoxycarbonyl-1-[5'-O-(4,4'-dimethoxy triphenylmethyl)-2'-deoxy-3'-O-(4-nitrobenzenesulfonyl)-beta-d-threopentofuranosyl]thymine (15mg) as the precursor molecule with [(18)F]fluoride, and subsequent hydrolysis of the protecting group with 1.0M HCl at the same reaction vessel and purification with SEP PAK cartridges instead of the HPLC system. RESULTS: The automated synthesis of [(18)F]FLT with SEP PAK purification gave corrected radiochemical yield of 23.2+/-2.6% (n=6, uncorrected yield: 16-22%) and radiochemical purity of >97% within the total synthesis time of 35min. CONCLUSION: The fully one-pot automated synthesis procedure with SEP PAK purification can be applied to the fully automated synthesis of [(18)F]FLT using commercial [(18)F]FDG synthesis module.

A simplified one-pot automated synthesis of [18F]FHBG for imaging reporter gene expression.

BACKGROUND: 9-(4-[F]fluoro-3-hydroxymethylbutyl) guanine ([F]FHBG) has been used as a reporter probe to image the expression of the herpes simplex virus type 1 thymidine kinase (TK) reporter gene in living organisms with positron emission tomography (PET). However, the routine production of [F]FHBG presents many challenging laboratory requirements. AIM: To develop a simple one-pot fully-automated synthesis procedure of [F]FHBG amenable for its routine use in reporter gene expression PET imaging studies. METHODS: A TRACERlab FXF-N synthesizer was substantially modified and adapted to the synthesis of [F]FHBG through the two-step one-pot procedure. After the fluorination reaction of the tosylate precursor and the hydrolysis of the intermediate product in the same reaction vessel, the final product was purified by Sep-Pak cartridges instead of the high performance liquid chromatography system. RESULTS: The fully automated synthesis of [F]FHBG with Sep-Pak purification was performed within a short synthesis time. The decay-uncorrected radiochemical yield of [F]FHBG was 8-14% (n=10), the radiochemical purity was more than 99%, and the entire synthesis time was less than 40 min. In addition, the PET image of theTK-transfected nude mice model indicated a much higher uptake of [F]FHBG in the TK-transfected tumor region than in the control tumor region. CONCLUSION: The automated synthesis of [F]FHBG is very easy to carry out using one-pot reactions combined with Sep-Pak purification. The synthetic [F]FHBG can be used for PET imaging and monitoring of in vivo herpes simplex virus type 1 TK gene expression.