Effects of Mechanical Properties on Gas-Water Flow Characteristics around Boreholes: Implementation of Damage-Based Coupling Models.

Neglecting the coal damage effect around a borehole could result in low accuracy of gas extraction seepage analysis. A fluid-solid coupling model incorporating coal stress and damage, gas diffusion, and seepage was established. Reliability of the proposed model was validated using field data. Variation characteristics of gas-water phase parameters in the borehole damage zone during gas drainage were analyzed. Meanwhile, effects of equivalent plastic strain, lateral pressure coefficient, internal friction angle, cohesion, Young's modulus, and Poisson's ratio on the damage state and spatiotemporal change properties of gas extraction flow were investigated. Results indicate that due to coal damage, permeability shows a three-zone distribution around the borehole, among which the fracture zone has the highest permeability, approximately 40 times of the original value. Permeability in the plastic zone decreases rapidly, while permeability is the smallest in the elastic zone. Coal permeability within the damage zone increases with continuous gas extraction. A smooth and low-value zone occurs for both fracture and matrix gas pressures. With the increase in equivalent plastic strain, the damage zone decreases, while peak permeability in the damage zone rises, and gas pressure in the smooth low-pressure zone continues to drop. The damage zone becomes smaller with an increasing lateral pressure coefficient, while those plastic and elastic zones become larger. The damage zone area corresponding to the lateral pressure coefficient of 0.89 is 82.3% smaller compared with that of 0.56. As internal friction angle and cohesion rise, the damage zone gradually decreases and shifts from a butterfly shape to elliptical shape. When Young's modulus is heterogeneously distributed, except for concentrated shear damage zones around the borehole, punctate microdamage zones are also found at positions far from the borehole. Those damage zones gradually become smaller as shape parameters of the Weibull distribution get larger. The above findings are expected to offer theoretical support and practical guidance for borehole drilling and efficient extraction of clean methane resources.

Feasibility of baculovirus-mediated reporter gene delivery for efficient monitoring of islet transplantation in vivo.

OBJECTIVE: The objective of this study was to explore the feasibility of baculovirus vector-mediated sodium iodide symporter (NIS) gene delivery to monitor islet transplantation. METHODS: Baculovirus vectors expressing green fluorescent protein (GFP) or NIS (Bac-GFP and Bac-NIS) were established using the Bac-to-Bac baculovirus expression system. The GFP expression of Bac-GFP-infected rat islets was observed in vitro by fluorescence microscopy. Iodine uptake and inhibition of iodine uptake by NaClO4 in Bac-NIS-infected islets were dynamically monitored in vitro. Bac-GFP- or Bac-NIS-infected islets were implanted into the left axillary cavity of NOD-SCID mice, and fluorescence imaging and (125)I NanoSPECT/CT imaging were subsequently performed in vivo. RESULTS: Bac-GFP efficiently infected rat islets (over 95% infected at MOI=40), and the expression of GFP lasted approximately two weeks. NaClO4 could inhibit iodine uptake by Bac-NIS-infected islets. In vivo imaging revealed that the fluorescence intensity of the transplant sites in Bac-GFP-infected groups was significantly higher than in the non-infected group. Grafts could be clearly observed by (125)I NanoSPECT/CT imaging for up to 8 h. CONCLUSION: Baculovirus vectors are powerful vehicles for studying rat islets in gene delivery. It is feasible to use a baculovirus vector to delivery an NIS gene for non-invasive monitoring transplanted islets in vivo by the expression of the target gene.

Potential usefulness of baculovirus-mediated sodium-iodide symporter reporter gene as non-invasively gene therapy monitoring in liver cancer cells: an in vitro evaluation.

Primary liver cancer has one of the highest mortality rates of all cancers, and the main current treatments have a poor prognosis. This study aims to examine the efficiency of baculovirus vectors for transducing target gene into liver cancer cells and to evaluate the feasibility of using baculovirus vectors to deliver the sodium-iodide symporter (NIS) gene as a reporter gene through co-vector administration approach to monitor the expression of the target therapeutic gene in liver cancer gene therapy. We constructed (green fluorescent protein) GFP- and NIS-expressing baculovirus vectors (Bac-GFP and Bac-NIS), and measured the baculovirus transduction efficiency in HepG2 cells and other tumor cells (A549, SW1116 and 8505C), and it showed that the transduction efficiency and target gene expression level rose with increasing viral multiplicity of infection (MOI) in HepG2 cells, and HepG2 cells had a significantly higher transduction efficiency (60.8% at MOI = 200) than other tumor cells. Moreover, the baculovirus transduction was not cytotoxic to HepG2 cells at a higher MOI (MOI 5 400). We also performed dynamic iodide uptake trials, and found that Bac-NIS-transduced HepG2 cells exhibited efficient iodide uptake which could be inhibited by sodium perchlorate (NaClO4). And we measured the correlation of fluorescent intensities and 125I uptake amount in HepG2 cells after co-vector administration with Bac-NIS and Bac-GFP at different MOIs, and found a high correlation coefficient (r(2) = 0.8447), which provides a good basis for successfully evaluating the feasibility of baculovirus-mediated NIS reporter gene monitoring target gene expression in liver cancer therapy. Therefore, this study indicates that baculovirus vector is a potential vehicle for delivering therapeutic genes in studying liver cancer cells. And it is feasible to use a baculovirus vector to deliver NIS gene as a reporter gene to monitor the expression of target genes. It therefore provides an effective approach and a good basis for future baculovirus-mediated therapeutic gene delivering or therapeutic gene expression monitoring in liver cancer cells studies.

Nabothian cyst associated with high false-positive incidence of iodine-131 uptake in whole-body scans after treatment for differentiated thyroid cancer.

OBJECTIVE: This study aimed to analyze the focal uptake of iodine-131 (131I) in the upper pelvis superior to the urinary bladder on whole-body images of patients who underwent this treatment after thyroidectomy for differentiated thyroid cancer. METHODS: Between June 2012 and March 2013, 205 patients (72 men and 133 women, with an average age of 47.9 ± 11.7 years) who underwent 131I radioactive treatment after thyroid cancer surgery were analyzed retrospectively. Pathological findings confirmed papillary thyroid carcinoma. A whole-body scan was acquired 5 days after 100-120 mCi sodium iodide was administered orally to the patients. Single-photon emission computed tomography/computed tomography (SPECT/CT) scanning was carried out to locate the lesion; this showed abnormal intense activity in the upper pelvis superior to the urinary bladder, which was further evaluated by ultrasonography. RESULTS: Using 131I-SPECT scanning, five (3.76%) female patients were shown to have abnormal focal radioactivity in the lower abdomen. Subsequent SPECT/CT examination showed that the radioactivity was located in the cervix in four of the five patients and in the sigmoid colon in one patient. Transvaginal ultrasonography was performed in the former four patients, which revealed several echo-free regions in the cervix. These findings are consistent with the diagnosis of a nabothian cyst. Three of these patients were administered a second course of radioiodine therapy. Radioactive uptake was still visible at the same sites on whole-body imaging. CONCLUSION: Nabothian cyst should be considered in cases in which abnormal uptake in the upper pelvis superior to the urinary bladder is detected on 131I whole-body scans after differentiated thyroid cancer resection.

18F-radiolabeled GLP-1 analog exendin-4 for PET/CT imaging of insulinoma in small animals.

BACKGROUND: Insulinoma is a neuroendocrine tumor derived from the ß cells of pancreatic islets. They are usually relatively inaccessible for surgical intervention. High expression levels of glucagon-like peptide-1 (GLP-1) receptor have been detected in insulinoma. AIM: The aim of the study was to evaluate the potential of F-radiolabeled GLP-1 analog exendin-4 for the diagnosis of insulinoma using PET/computed tomography imaging. MATERIALS AND METHODS: The GLP-1 receptor-specific molecular probe [F]FB-exendin-4 was prepared by the conjugation of exendin-4 and N-succinimidyl-4-[F] fluorobenzoate ([F]SFB). High expression of GLP-1 by the RIN-m5f insulinoma line and GLP-1 receptor specificity were evaluated by determining the saturation curve for in-vitro binding of I-radiolabeled exendin-4 and by investigation of the competitive binding between I-radiolabeled and unlabeled exendin-4. Further, the in-vivo biodistribution and micro-PET/computed tomography images of insulinoma-bearing mice were studied. RESULTS: An overall radiochemical yield of 35.6±2.3% (decay corrected, n=5) and specific radioactivity of around 30 GBq/µmol were achieved for [F]FB-exendin-4, and the radiochemical purity was over 98%. Both in-vitro and in-vivo studies confirmed the specificity of [F]FB-exendin-4 to insulinoma cells. CONCLUSION: [F]FB-exendin-4 has been found to be an effective molecular imaging probe for detecting insulinomas.

Baculovirus as an ideal radionuclide reporter gene vector: a new strategy for monitoring the fate of human stem cells in vivo.

PURPOSE: Radionuclide reporter gene imaging holds promise for non-invasive monitoring of transplanted stem cells. Thus, the feasibility of utilizing recombinant baculoviruses carrying the sodium iodide symporter (NIS) reporter gene in monitoring stem cell therapy by radionuclide imaging was explored in this study. METHODS: Recombinant baculoviruses carrying NIS and green fluorescent protein (GFP) reporter genes (Bac-NIS and Bac-GFP) were constructed and used to infect human induced pluripotent stem cells (hiPSCs), human embryonic stem cells (hESCs) and human umbilical cord blood mesenchymal stem cells (hUCB-MSCs). Infection efficiency, total fluorescence intensity and duration of transgene expression were determined by flow cytometry. Cytotoxicity/proliferative effects of baculovirus on hUCB-MSCs were assessed using CCK-8 assays. ¹²5I uptake and perchlorate inhibition assays were performed on Bac-NIS-infected hUCB-MSCs. Radionuclide imaging of mice transplanted with Bac-NIS-infected hUCB-MSCs was performed by NanoSPECT/CT imaging. RESULTS: Infection efficiencies of recombinant baculovirus in hESCs, hiPSCs and hUCB-MSCs increased with increasing MOIs (27.3%, 35.8% and 95.6%, respectively, at MOI = 800). Almost no cytotoxicity and only slight effects on hUCB-MSCs proliferation were observed. Obvious GFP expression (40.6%) remained at 8 days post-infection. The radioiodide was functionally accumulated by NIS gene products and specifically inhibited by perchlorate (ClO4⁻). Radioiodide uptake, peaking at 30 min and gradually decreasing over time, significantly correlated with hUCB-MSCs cell number (R²â€Š= 0.994). Finally, radionuclide imaging showed Bac-NIS-infected hUCB-MSCs effectively accumulated radioiodide in vivo, which gradually weakened over time. CONCLUSION: Baculovirus as transgenic vector of radionuclide reporter gene imaging technology is a promising strategy for monitoring stem cell transplantation therapy.

Diagnosis of multiple endocrine neoplasia type 2A in patients with positive thyroid imaging by iodine-131 metaiodobenzylguanidine scintigraphy.

We retrospectively analyzed iodine-131 metaiodobenzylguanidine (I-131 MIBG) scintigraphy in 320 patients (male, 108 cases; female, 211 cases; average age, 45±15 years). All patients received thyroid block before examination between 2007 and 2010 in our department. Various degrees of radioactivity were found in the thyroid glands or thyroid region after bilateral thyroid surgery, in addition to bilateral or unilateral abnormal radioactivity in the adrenal glands in 3 patients. These cases were confirmed for medullary thyroid carcinoma and adrenal pheochromocytoma by pathology after surgical removal of the glands, and the diagnosis of multiple endocrine neoplasia type 2A was established from the patients' history and genetic examination. The possibility of medullary thyroid carcinoma should be considered on the finding of abnormal radioactivity in the thyroid or thyroid region by I-131 MIBG scintigraphy after excluding normal radioactivity in the thyroid. When significant abnormal radioactivity is seen in the adrenal gland on I-131 MIBG scintigraphy, the possibility of adrenal pheochromocytoma should be considered. Adrenal pheochromocytoma cannot be excluded when adrenal uptake is increased. The possibility of multiple endocrine neoplasia type 2A should be considered taking into account the history of these patients.

Baculovirus vector-mediated transfer of NIS gene into colon tumor cells for radionuclide therapy.

AIM: To investigate the feasibility of radionuclide therapy of colon tumor cells by baculovirus vector-mediated transfer of the sodium/iodide symporter (NIS) gene. METHODS: A recombinant baculovirus plasmid carrying the NIS gene was constructed, and the viruses (Bac-NIS) were prepared using the Bac-to-Bac system. The infection efficiency in the colon cancer cell line SW1116 of a green fluorescent protein (GFP) expressing baculovirus (Bac-GFP) at different multiplicities of infection (MOI) with various concentrations of sodium butyrate was determined by flow cytometry. An in vitro cytotoxicity assay was also conducted after infection of SW1116 cells with Bac-NIS. Iodine uptake of Bac-NIS infected SW1116 cells and inhibition of this uptake by sodium perchlorate was examined, and the effect of Bac-NIS-mediated (131)I in killing tumor cells was evaluated by cell colony formation tests. RESULTS: Infection and transgene expression in SW1116 with Bac-GFP were significantly enhanced by sodium butyrate, as up to 72% of SW1116 cells were infected with the virus at MOI of 400 and sodium butyrate at 0.5 mmol/L. No obvious cytotoxicity was observed under these conditions. Infection of SW1116 with Bac-NIS allowed uptake of (131)I in these tumor cells, which could be inhibited by sodium perchlorate. The viability of SW1116 cells infected with Bac-NIS was significantly lower than with Bac-GFP, suggesting that NIS gene-mediated (131)I uptake could specifically kill tumor cells. CONCLUSION: Baculovirus vector-mediated NIS gene therapy is a potential approach for treatment of colon cancer.