Hepatic VIC showed significant correlation with R2* and MR-measured LIC (r = 0.885 and 0.871, respectively; P < .0001). To differentiate among different LIC thresholds of 1.8, 3.2, 7.0, and 15.0 mg of iron per gram of dry tissue, the corresponding optimal cutoff values for VIC were 2.50, 5.13, 8.93, and 17.97 HU, respectively. At a LIC threshold of 7.0 mg of iron per gram of dry tissue or higher, 100% sensitivity (15 of 15 patients) and 100% specificity (19 of 19 patients) were obtained for VIC. There was no significant difference between VIC and R2* (area under the ROC curve, 0.964 vs 0.993, respectively; P = .299) in grading LIC levels at a LIC threshold of 3.2 mg of iron per gram of dry tissue or higher. Conclusion Hepatic VIC is a potential index for accurately evaluating and grading clinically significant liver iron accumulation, with a diagnostic performance similar to that of MR imaging.
Background Sodium/iodide symporter (NIS)-mediated iodide uptake plays an important physiological role in regulating thyroid gland function, as well as in diagnosing and treating Graves’ disease and thyroid cancer. High-mobility group box 1 (HMGB1), a highly conserved nuclear protein, is a positive regulator of autophagy conferring resistance to chemotherapy, radiotherapy and immunotherapy in cancer cells. Here the authors intended to identify the role of HMGB1 in Hank’s balanced salt solution (HBSS)-induced autophagy, explore NIS protein degradation through a autophagy-lysosome pathway in thyroid cancer cells and elucidate the possible molecular mechanisms. Methods Immunohistochemical staining and reverse transcription-polymerase chain reaction (RT-PCR) were performed for detecting the expression of HMGB1 in different tissues. HMGB1 was knocked down by lentiviral transfection in FTC-133/TPC-1 cells. Autophagic markers LC3-II, p62, Beclin1 and autophagosomal formation were employed for evaluating HMGB1-mediated autophagy in HBSS-treated cells by Western blot, immunofluorescence and electron microscopy. Western blot, quantitative RT-PCR and gamma counter analysis were performed for detecting NIS expression and iodide uptake in HMGB1-knockdown cells after different treatments. The reactive oxygen species (ROS) level, ROS-mediated LC3-II expression and HMGB1 cytosolic translocation were detected by fluorospectrophotometer, flow cytometry, Western blot and immunofluorescence. HMGB1-mediated AMPK, mTOR and p70S6K phosphorylation (p-AMPK, p-mTOR & p-p70S6K) were detected by Western blot. Furthermore, a nude murine model with transplanted tumor was employed for examining the effect of HMGB1-mediated autophagy on imaging and biodistribution of 99m TcO4 − . NIS, Beclin1, p-AMPK and p-mTOR were detected by immunohistochemical staining and Western blot in transplanted tumor samples. Results HMGB1 was a critical regulator of autophagy-mediated NIS degradation in HBSS-treated FTC-133/TPC-1 cells. And HMGB1 up-regulation was rather prevalent in thyroid cancer tissues and closely correlated with worse overall lymph node metastasis and clinical stage. HMGB1-knockdown dramatically suppressed autophagy, NIS degradation and boosted iodide uptake in HBSS-treated cells. Moreover, HBSS enhanced ROS-sustained autophagy and promoted the cytosolic translocation of HMGB1. A knockdown of HMGB1 suppressed LC3-II conversion and NIS degradation via an AMPK/mTOR-dependent signal pathway through a regulation of ROS generation, rather than ATP. Furthermore, these data were further supported by our in vivo experiment of xenografts formed by HMGB1 knockdown cells reverting the uptake of 99m TcO4 − as compared with control shRNA-transfected cells in hunger group. Conclusions Acting as a critical regulator of autophagy-mediated NIS degradati...
Rationale:Displacement of an intrauterine contraceptive device (IUD) is a rare and serious complication of IUD insertion. Theoretically, it can migrate to anywhere in the pelvic and abdominal cavity. However, it is not usual for an IUD to migrate to the bladder.Patient concerns:In this case report, we reported a patient with chronic urinary symptoms caused by the migration of an IUD into the bladder. The displacement of the IUD led to contraception failure and IUD retention in the bladder for 5 years.Diagnoses:Pelvic ultrasonography (US), radiography, and cystoscopy examinations confirmed the migration of IUD in bladder.Interventions:The patient underwent cystoscopy.Outcomes:The MCu IUD was successfully removed without any complications.Lessons:Our study demonstrated that a missing IUD should be followed up and removed early to avoid possible serious complications.
Differentiation therapy based on all-trans-retinoic acid (ATRA) and arsenic trioxide (ATO) for the treatment of acute promyelocytic leukemia (APL) is complicated by the development of differentiation syndrome (DS), which can be fatal. We examined the role of HMGB1 (high-mobility group box 1) in DS using both in vitro and in vivo models. HMGB1 and the pro-inflammatory cytokines IL-1β and TNF-α were gradually released from NB4 and HL-60 cells treated with ATRA and/or ATO. Similarly, higher serum HMGB1 levels positively correlated with the clinical status of DS patients. Exogenous HMGB1 promoted rapid release of IL-1β and TNF-α as well as elevated expression of ICAM-1, without altering cell differentiation. Exogenous HMGB1 also enhanced pulmonary infiltration and up-regulated ICAM-1 expression in the ATRA-treated DS mouse. Pharmacological inhibition or depletion of MEK1/2 reduced the cytokine levels and suppressed expression of ICAM-1 and the adhesion of HMGB1-treated NB4 cells to endothelial cells, implicating MEK/ERK signaling in the response to HMGB1 during DS. Treatment with a HMGB1-neutralizing antibody reduced secretion of TNF-α and IL-1β, arrested the elevation of ICAM-1 and blunted the activation of ERK1/2 in ATRA-induced NB4 cells. The HMGB1-neutralizing antibody also decreased ICAM-1 expression and reduced mortality in ATRA-treated DS model mice. These findings demonstrate that released HMGB1 is central to DS, and that targeting HMGB1 may be of therapeutic value in the treatment of DS.
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