Ginsenoside Rg3 promotes hepatic stellate cell ferroptosis by epigenetically regulating ACSL4 to suppress liver fibrosis progression.

BACKGROUND: Ginsenoside Rg3 (G-Rg3), extracted from Panax notoginseng, possesses hepatoprotective properties. Hepatic stellate cells (HSCs) activation is responsible for liver fibrosis. Recent studies have reported the suppressive effects of G-Rg3 on HSC activation and proliferation. Ferroptosis is a novel iron regulated cell death. ACSL4, a key indicator of ferroptosis, is commonly methylated in various diseases. PURPOSE: However, the role of ACSL4 methylation-mediated HSC ferroptosis in G-Rg3 inhibition of hepatic fibrosis needs to be explored. METHODS: Effects of G-Rg3 on inhibiting fibrosis were evaluated in vivo and in vitro. The impact of G-Rg3 on HSC ferroptosis was assessed in vitro. Furthermore, the expression of ACSL4, ACSL4 methylation and microRNA-6945-3p (miR-6945-3p) levels were determined. RESULTS: G-Rg3 significantly alleviated CCl4-induced liver fibrosis, accompanied by collagen downregulation. In vitro, G-Rg3 contributed to HSC inactivation, leading to decreased collagen production. G-Rg3 induced HSC ferroptosis, characterized by increased iron accumulation, depletion of glutathione, malondialdehyde levels, and generation of lipid reactive oxygen species. Moreover, G-Rg3 promoted ACSL4 demethylation and restored its expression. Notably, DNMT3B counteracted the effect of G-Rg3-mediated inhibition of ACSL4 methylation and was targeted by miR-6945-3p. Further investigations revealed that G-Rg3 suppressed ACSL4 methylation through miR-6945-3p-mediated DNMT3B inhibition. Consistent with this, miR-6945-3p inhibition reversed G-Rg3-induced ACSL4 expression and HSC ferroptosis. CONCLUSION: G-Rg3 inhibits ACSL4 methylation by miR-6945-3p-mediated DNMT3B inhibition, thereby promoting HSC ferroptosis and mitigating liver fibrosis.

Preparation, characterization and immune response of chitosan­gold loaded Myricaria germanica polysaccharide.

In this study, a novel nano-drug delivery system (CS-Au NPs) based on gold nanoparticles (Au NPs) and chitosan (CS) that modified Myricaria germanica polysaccharide (MGP) was developed to enhance immune responses. At a MGP to CS Au ratio of 5:1, CS-Au-MGP NPs had a loading capacity of 78.27 %. The structure of CS-Au-MGP NPs were characterized by Transmission electron microscope, TEM-energy dispersive spectroscopy mapping, Fourier transform infrared spectroscopy, X-ray photoelectron spectrometer, particle size and zeta-potential distribution analysis. Under weakly acidic conditions, in vitro CS-Au-MGP NPs release was most effective. In vivo showed that co-immunization with CS-Au-MGP NPs and PCV2 significantly increased the organ index of the thymus, spleen, and liver in mice. Additionally, CS-Au-MGP NPs significantly increased the levels of IgG, IgG1, and IgG2a antibodies, as well as IFN-γ and IL-6 levels. Furthermore, the CS-Au-MGP NPs promoted proliferation of spleen T and B lymphocytes, increased the number of CD3+, CD4+, and CD8+ cells, and increased the CD4+/CD8+ T cell ratio. Meanwhile, CS-Au-MGP NPs remarkably TLR2/IRAK4 pathway activation and mRNA levels of cytokines (IFN-γ and IL-6). These results indicated that CS-Au-MGP NPs could enhance the immune activity, and it could be potentially used as an MGP delivery system for the induction of strong immune responses.

Serum ribonucleotide reductase M2 is a potential biomarker for diagnosing and monitoring liver fibrosis in chronic hepatitis B patients.

It is known that ribonucleotide reductase M2 (RRM2) could be induced by hepatitis B virus (HBV) via DNA damage response. However, whether RRM2 is a potential biomarker for diagnosing and monitoring liver fibrosis in chronic hepatitis B (CHB) patients is still unclear. In this study, CHB patients from GSE84044 (a transcriptome data from GEO data set) were downloaded and RRM2 was selected as a hub gene. Interestingly, a positive correlation was found between serum RRM2 and liver fibrosis stage. The similar results were found in CHB patients with normal alanine aminotransferase (ALT). Notably, RRM2 could effectively differentiate preliminary fibrosis from advanced fibrosis in CHB patients with/without normal ALT. In addition, RRM2 had a better performance in diagnosing liver fibrosis than two commonly used noninvasive methods (aspartate aminotransferase-to-platelet ratio index and fibrosis index based on the four factors), two classic fibrotic biomarkers (hyaluronic acid and type IV collagen) as well as Mac-2 binding protein glycosylation isomer, a known serum fibrosis marker. Moreover, CHB patients with high RRM2, who were associated with advanced fibrosis, had higher expressions of immune checkpoints. Overall, serum RRM2 may be a promising biomarker for diagnosing and monitoring liver fibrosis in CHB patients.

Exploration and validation of a novel signature of seven necroptosis-related genes to improve the clinical outcome of hepatocellular carcinoma.

Necroptosis has been reported to be involved in cancer progression and associated with cancer prognosis. However, the prognostic values of necroptosis-related genes (NRGs) in hepatocellular carcinoma (HCC) remain largely unknown. This study aimed to build a signature on the basis of NRGs to evaluate the prognosis of HCC patients. In this study, using bioinformatic analyses of transcriptome sequencing data of HCC (n = 370) from The Cancer Genome Atlas (TCGA) database, 63 differentially expressed NRGs between HCC and adjacent normal tissues were determined. 24 differentially expressed NRGs were found to be related with overall survival (OS). Seven optimum NRGs, determined using Lasso regression and multivariate Cox regression analysis, were used to construct a new prognostic risk signature for predicting the prognosis of HCC patients. Then survival status scatter plots and survival curves demonstrated that the prognosis of patients with high-Riskscore was worse. The prognostic value of this 7-NRG signature was validated by the International Cancer Genome Consortium (ICGC) cohort and a local cohort (Wenzhou, China). Notably, Riskscore was defined as an independent risk factor for HCC prognosis using multivariate cox regression analysis. Immune infiltration analysis suggested that higher macrophage infiltration was found in patients in the high-risk group. Finally, enhanced 7 NRGs were found in HCC tissues by immunohistochemistry. In conclusion, a novel 7-NRG prognostic risk signature is generated, which contributes to the prediction in the prognosis of HCC patients for the clinicians.

Hepatocyte-derived exosomal miR-146a-5p inhibits hepatic stellate cell EMT process: a crosstalk between hepatocytes and hepatic stellate cells.

Recently, Salidroside (Sal) has been demonstrated to suppress hepatic stellate cell (HSC) activation, a crucial event for liver fibrosis. Moreover, Sal has been reported to decrease hepatocyte injury. A growing number of reports have indicated that the crosstalk between hepatocytes and HSCs is very crucial for liver fibrosis development. Whether Sal-treated hepatocytes could inhibit HSC activation is unclear. Exosomes, as vital vehicles of intercellular communication, have been shown to transfer cargos between hepatocytes and HSCs. Herein, we aimed to investigate the roles of exosomal miRNAs from Sal-treated hepatocytes in HSC activation as well as liver fibrosis. Our results showed that Sal suppressed carbon tetrachloride (CCl4)-induced liver fibrosis in vivo. HSC activation as well as cell proliferation was repressed in HSCs co-cultured with Sal-treated hepatocytes. Interestingly, miR-146a-5p was up-regulated by Sal in CCl4-treated mice. Also, enhanced miR-146a-5p was found in hepatocytes isolated from Sal-treated CCl4 mice and hepatocyte-derived exosomes. Notably, hepatocyte exosomal miR-146a-5p contributed to HSC inactivation. Inhibiting miR-146a-5p in hepatocyte exosomes resulted in reduced E-cadherin (E-cad) and increased desmin in HSCs, indicating that miR-146a-5p caused HSC inactivation via epithelial-mesenchymal transition (EMT). miR-146a-5p inhibition-mediated HSC activation and EMT process were blocked down by loss of EIF5A2. Further studies revealed that EIF5A2 was a target of miR-146a-5p. Furthermore, exosomes with miR-146a-5p overexpression inhibited liver fibrosis in CCl4 mice. Collectively, exosomal miR-146a-5p from Sal-treated hepatocytes inhibits HSC activation and liver fibrosis, at least in part, by suppressing EIF5A2 and EMT process.

Machine learning integrations develop an antigen-presenting-cells and T-Cells-Infiltration derived LncRNA signature for improving clinical outcomes in hepatocellular carcinoma.

As a highly heterogeneous cancer, the prognostic stratification and personalized management of hepatocellular carcinoma (HCC) are still challenging. Recently, Antigen-presenting-cells (APCs) and T-cells-infiltration (TCI) have been reported to be implicated in modifying immunology in HCC. Nevertheless, the clinical value of APCs and TCI-related long non-coding RNAs (LncRNAs) in the clinical outcomes and precision treatment of HCC is still obscure. In this study, a total of 805 HCC patients were enrolled from three public datasets and an external clinical cohort. 5 machine learning (ML) algorithms were transformed into 15 kinds of ML integrations, which was used to construct the preliminary APC-TCI related LncRNA signature (ATLS). According to the criterion with the largest average C-index in the validation sets, the optimal ML integration was selected to construct the optimal ATLS. By incorporating several vital clinical characteristics and molecular features for comparison, ATLS was demonstrated to have a relatively more significantly superior predictive capacity. Additionally, it was found that the patients with high ATLS score had dismal prognosis, relatively high frequency of tumor mutation, remarkable immune activation, high expression levels of T cell proliferation regulators and anti-PD-L1 response as well as extraordinary sensitivity to Oxaliplatin/Fluorouracil/Lenvatinib. In conclusion, ATLS may serve as a robust and powerful biomarker for improving the clinical outcomes and precision treatment of HCC.

LncRNA-MIAT activates hepatic stellate cells via regulating Hippo pathway and epithelial-to-mesenchymal transition.

Long non-coding RNA-myocardial infarction-associated transcript (lncRNA-MIAT) has been reported to play an important role in the development of multiple cancers. However, the biological roles of MIAT in liver fibrosis are still unknown. In this study, the expression of MIAT is up-regulated during liver fibrosis. Silencing MIAT leads to the suppression of hepatic stellate cell (HSC) proliferation and collagen expression. Double immunofluorescence analysis additionally demonstrates that MIAT inhibition leads to the suppression of type I collagen and α-SMA in vitro. In vivo, MIAT knockdown contributes to the inhibition of fibrosis progression and collagen accumulation. MIAT is confirmed as a target of miR-3085-5p, and the co-location of MIAT and miR-3085-5p is found in HSC cytoplasm. Interestingly, there is a negative correlation between MIAT expression and miR-3085-5p level in cirrhotic patients as well as activated HSCs. In addition, the effects of MIAT inhibition on HSC inactivation are blocked down by miR-3085-5p inhibitor. YAP is a target of miR-3085-5p. Reduced YAP caused by loss of MIAT is reversed by miR-3085-5p inhibitor. Notably, YAP knockdown results in the suppression of MIAT-mediated epithelial-to-mesenchymal transition (EMT) process. In conclusion, we demonstrate that MIAT enhances the activation of HSCs, at least in part, via miR-3085-5p/YAP/EMT signaling pathway.

18 F-FDG PET/CT imaging for haemophilic arthropathy compared with clinical, radiological and power Doppler sonographic characteristics of 20 haemophilia patients.

INTRODUCTION AND OBJECTIVES: Repeated joint bleeding in haemophilia patients may lead to haemophilic arthropathy with marked inflammation and synovitis. This study investigated the potential of 18 F-fluorodeoxyglucose positron emission tomography-computed tomography (18 F-FDG PET/CT) as a novel diagnostic method for haemophilic arthropathy. MATERIALS AND METHODS: We recruited 20 adult haemophilia patients who reported history of hemarthroses in the shoulder, elbow, hip, knee, or ankle joints. All joints were assessed by power Doppler ultrasonography and radiography, and graded by hyperaemia score and Pettersson score, respectively. Joint pain was evaluated by visual analogue score (VAS). Range of motion (ROM), Haemophilia Joint Health Score (HJHS) and annual joint bleeding rate (AJBR) were recorded. Finally, all participants had whole-body 18 F-FDG PET/CT, and maximum standardized uptake value (SUVmax) of the joints being studied was measured. RESULTS: Thirteen patients had severe haemophilia, and seven had moderate haemophilia. The mean age was 36 years. PET SUVmax showed significant correlations with VAS, ROM, Pettersson score, hyperaemia score, HJHS score and AJBR in all large joints except hip. Joints with pain, hyperaemia and radiographic changes were found to have higher SUVmax than those without these features. Using Youden's index, the optimal cut-off value for early radiographical arthropathy was found to be between 1.9 and 2.0. CONCLUSION: Our study indicates that 18 F-FDG PET/CT imaging correlated well with various conventional diagnostic techniques. It also demonstrated high sensitivity and specificity for early radiographic arthropathy. 18 F-FDG PET/CT imaging may quantitatively evaluate disease activity of most large joints in a single examination and help detect early haemophilic arthropathy.

A comprehensive study based on exosome-related immunosuppression genes and tumor microenvironment in hepatocellular carcinoma.

BACKGROUND: Exosomes play an important role in the tumor microenvironment (TME) and the mechanisms of tumor immune escape in hepatocellular carcinoma (HCC). It is known that immunosuppressive genes, involved in the processes of tumor immunosuppression, are associated with cancer progression. This study aimed to explore the prognostic values of exosome-related immunosuppression genes (ERIGs) in HCC. METHODS: The RNA-seq transcriptome data of 374 HCC patients were obtained from the Cancer Genome Atlas (TCGA) database. The TCGA cohort was randomly divided into the training cohort and validation cohort in a 1:1 ratio. WGCNA analysis and Pearson correlation analysis were used to identify ERIGs. The Lasso regression method was used to construct a 5-ERIG signature. The prognostic value of our signature was examined in the First Affiliated Hospital of Wenzhou Medical University (FAHWMU) cohort. RESULTS: Univariate Cox regression analysis was used to screen prognostic ERIGs. Subsequently, these prognostic ERIGs were included in Lasso regression analyses to identify 5 key ERIGs (ASAP1, IARS1, GTF3C2, TPD5L2 and SLC52A2) and construct a 5-ERIG signature. The patients in the low-risk group had better prognosis than those in the high-risk group. Univariate and multivariate cox regression revealed that risk score was an independent prognostic risk factor of HCC. Gene set enrichment analysis (GSEA) showed that this signature was highly associated with TME-related pathways. Subsequent analyses revealed the potential role of the signature in regulating the TME in HCC. In addition, a lower immunotherapy score was found in patients with high risk-score. Of note, this signature was confirmed to have a good performance in predicting HCC prognosis in the FAHWMU cohort. Moreover, knockdown of 5 ERIGs of this signature contributed to the suppression the Hep3B cell proliferation. CONCLUSIONS: We generated a novel prognostic 5-ERIG signature to accurately predict the prognosis of patients with HCC, and this signature may serve as an indicator of immunotherapy for HCC.

Kaempferol Inhibits Hepatic Stellate Cell Activation by Regulating miR-26b-5p/Jag1 Axis and Notch Pathway.

Kaempferol, a natural flavonoid molecule, has demonstrated anti-inflammatory, antimicrobial and antioxidant activities. Recent studies have shown the beneficial effects of kaempferol on liver fibrosis. Notch pathway has been reported to be involved in the aberrant activation of hepatic stellate cells (HSCs). However, whether Notch pathway plays a key role in the anti-fibrotic effects of kaempferol is largely unknown. In this study, kaempferol significantly suppressed liver fibrosis in CCl4 mice, with reduced collagen deposition as well as restored liver function. In vitro, kaempferol enhanced the suppression of HSC activation, with a decrease in α-SMA as well as collagen level. It was found that Notch pathway played an important role in kaempferol-reduced the activation of HSCs. Jag1, a ligand of Notch pathway, was obviously inhibited by kaempferol. Overexpression of Jag1 effectively abolished kaempferol-induced HSC inactivation. Furthermore, Jag1 was demonstrated as a target of microRNA-26b-5p (miR-26b-5p). Interestingly, miR-26b-5p inhibitor prevented HSC activation inhibition caused by kaempferol. Further studies indicated that kaempferol inhibited Notch pathway via miR-26b-5p and Jag1, leading to HSC inactivation. Collectively, we demonstrate that kaempferol could inhibit HSC activation, at least in part, via miR-26b-5p-mediated Jag1 axis and Notch pathway. Kaempferol may serve as a promising drug in the application of treating liver fibrosis.

Radioactive Iodine Treatment for Thyroid Cancer Patients Increases the Risk of Long-Term Gastrointestinal Disorders: A Nationwide Population-Based Cohort Analysis.

(1) Background: The study aimed to investigate the association between radioactive iodine (RAI) treatment and long-term gastrointestinal disorders including ulcers, atrophic gastritis, and secondary malignant neoplasm of the stomach in patients with thyroid cancer. (2) Methods: The data of the study were extracted from the National Health Insurance Database (NHIRD) of Taiwan between 2000 to 2015. Patients of ages older than 20 with thyroid cancer after thyroidectomy were included and divided into groups with RAI (study cohort) and without RAI (comparison cohort). Multivariate Cox proportional hazards regression analysis and the Kaplan-Meier method were used for statistical analysis. (3) Results: A total of 7250 (with RAI: 5800, without RAI: 1450) patients were included. The Kaplan-Meier analysis revealed a significantly higher cumulative risk for overall gastrointestinal disorders in the group with RAI (log-rank p = 0.034). The risk for gastrointestinal disorders was higher when receiving a cumulative RAI dose higher than 1.11 GBq in the Cox regression analysis. In the subgroup analysis, the risks of gastric and duodenal ulcers are significantly higher in the group with RAI treatment. (4) Conclusions: This study revealed that RAI was associated with an increased risk for long-term gastrointestinal disorders, specifically gastric and duodenal ulcers, in thyroid cancer, especially when the cumulative dose exceeds 1.11 GBq.

Bezafibrate Exerts Neuroprotective Effects in a Rat Model of Sporadic Alzheimer's Disease.

Bezafibrate, a pan-peroxisome proliferator-activated receptor (PPAR) agonist, reportedly attenuated tau pathology in a transgenic mouse model of primary tauopathy. Since tau pathology is a neuropathological hallmark of Alzheimer's disease (AD), bezafibrate may be a potential drug for the treatment of AD. However, no study has investigated its effects in AD models. Thus, we aimed to evaluate whether bezafibrate has neuroprotective effects in a sporadic AD model induced by streptozotocin (STZ) intracerebroventricular (ICV) injection. Rats were administered STZ-ICV (3 mg/kg) followed by bezafibrate (50 mg/kg/day, intraperitoneal) for 4 weeks. Behavior tests and positron emission tomography (PET) were performed to evaluate longitudinal changes in cognitive function, tau pathology, and cerebral glucose metabolism. Immunofluorescence staining was performed to assess neuronal survival and microglial accumulation. STZ-ICV administration induced significant cognitive impairment and substantial neuronal loss, tau pathology, glucose hypometabolism, and microgliosis in the cortex and hippocampus, while bezafibrate effectively attenuated these abnormalities. This study demonstrated that bezafibrate has long-lasting neuroprotective effects in a sporadic AD model. Our data indicate that the neuroprotective effects of bezafibrate might be associated with its ability to ameliorate tau pathology, brain glucose hypometabolism, and neuroinflammation. These findings suggest that bezafibrate is a potential multi-target drug candidate for the treatment of AD.

Radioactive Iodine Treatment and the Risk of Long-Term Cardiovascular Morbidity and Mortality in Thyroid Cancer Patients: A Nationwide Cohort Study.

(1) Background: This study aimed to investigate the association between radioactive iodine (RAI) and long-term cardiovascular disease (CVD) morbidity/mortality in thyroid cancer. (2) Methods: The study was conducted using data from the Taiwan National Health Insurance Database during 2000-2015. Thyroid cancer patients aged ≥20 years were categorized into RAI (thyroidectomy with RAI) and non-RAI (thyroidectomy only) groups. The Cox proportional hazard regression model and Kaplan-Meier method were used for analysis. (3) Results: A total of 13,310 patients were included. Kaplan-Meier analysis demonstrated that the two groups had similar cumulative risks of CVD (log-rank p = 0.72) and CVD-specific mortality (log-rank p = 0.62). On Cox regression analysis of different RAI doses, the risk of CVD was higher in the cumulative dosage >3.7 GBq (hazard ratio = 1.69, 95% confidence interval = 1.24-2.40, p < 0.001). (4) Conclusions: RAI was not associated with an increased risk of CVD in thyroid cancer. However, CVD surveillance is indicated in the patients receiving the cumulative RAI dosage above 3.7 GBq.

A Pulmonary Pleomorphic Carcinoma Patient with Exudative Retinal Detachment Secondary to Choroid Metastasis as Initial Presentation-A Case Report.

Choroid metastasis is the initial presentation of pleomorphic carcinoma (PC) of the lung. PC is classified as poorly differentiated non-small cell lung carcinoma. It has a tendency to metastasize early and has a poor response to chemotherapy, which often results in poor prognosis. We report the case of a 63-year-old woman with a one-month history of deteriorating vision in the left eye. Fundus examination, fluorescein angiography, indocyanine green angiography, and B-scan sonography demonstrated choroidal metastasis of the left eye. Positron emission tomography/computed tomography (PET/CT) revealed a tumor with increased uptake in the left upper lung. Subsequent bronchoscopic biopsy confirmed a pleomorphic carcinoma of the lungs. Choroid metastasis as an initial presentation of PC in the lung is rare. Usually, it represents the late course of disseminated disease with hematogenous spread. Prompt diagnosis is imperative for patients to immediately initiate treatment.

Prognostic value of positron emission tomography in resected stage IA non-small cell lung cancer.

OBJECTIVES: To investigate the role of PET in predicting the prognosis of resected stage IA non-small cell lung cancer (NSCLC) and planning individualized therapeutic strategies. METHODS: We retrospectively reviewed the data of patients who underwent surgical resection for lung cancer between January 2004 and December 2014. The clinical data, imaging characteristics of nodules, surgical approaches, and outcomes were analyzed. RESULTS: We evaluated 998 cases; 637 patients with pathological stage I disease were categorized as follows: stage IA1 (251 cases), stage IA2 (250 cases), and stage IA3 (136 cases). The mean follow-up period was 109 months. Significant differences were observed in sex, tumor differentiation, epidermal growth factor receptor mutation, smoking habits, lymphovascular space invasion, tumor size, maximum standard uptake value (SUVmax), and carcinoembryonic antigen level among the groups. Multivariable Cox regression revealed that ground-glass opacity ratio (hazard ratio (HR) = 0.001) and tumor SUVmax independently predicted the postoperative risk of relapse for stage IA3 NSCLC. The HR for SUVmax > 4 was 8.986 (p < 0.001). The 5-year overall survival (OS) rates were 87.2%, 92.9%, and 82.7%, and the 5-year disease-free survival (DFS) rates were 93.2%, 84.2%, and 70.51% for stage IA1, IA2, and IA3 NSCLC, respectively (both p < 0.001). OS and DFS rates were poor in stage IA3 NSCLC patients with an SUVmax uptake > 4 (OS, 71.0% and 92.2%; DFS, 50.2% and 87.3%, for SUVmax > 4 and ≤ 4, respectively; both p = 0.001). CONCLUSIONS: SUVmax was a prognostic factor for resected stage IA NSCLC. Postoperative treatment may be considered for IA3 NSCLC with SUVmax > 4. KEY POINTS: • PET helps surgeons to assess patients with early-stage lung cancer. • This retrospective study revealed that PET plays an influential role in predicting the prognosis of resected lung cancer. • Better prognostication aids better planning of therapeutic strategies with diversification.

Image-based diagnosis of residual or recurrent nasopharyngeal carcinoma may be a phantom tumor phenomenon.

ABSTRACT: Some nasopharyngeal carcinoma (NPC) patients may present convincing radiological evidence mimicking residual or recurrent tumor after radiotherapy. However, by means of biopsies and long term follow-up, the radiologically diagnosed residuals/recurrences are not always what they appear to be. We report our experience on this "phantom tumor" phenomenon. This may help to avoid the unnecessary and devastating re-irradiation subsequent to the incorrect diagnosis.In this longitudinal cohort study, we collected 19 patients of image-based diagnosis of residual/recurrent NPC during the period from Feb, 2010 to Nov. 2016, and then observed them until June, 2019. They were subsequently confirmed to have no residual/recurrent lesions by histological or clinical measures. Image findings and pathological features were analyzed.Six patients showed residual tumors after completion of radiotherapy and 13 were radiologically diagnosed to have recurrences based on magnetic resonance imaging (MRI) criteria 6 to 206 months after radiotherapy. There were 3 types of image patterns: extensive recurrent skull base lesions (10/19); a persistent or residual primary lesion (3/19); lesions both in the nasopharynx and skull base (6/19). Fourteen patients had biopsy of the lesions. The histological diagnoses included necrosis/ inflammation in 10 (52.7%), granulation tissue with inflammation in 2, and reactive epithelial cell in 1. Five patients had no pathological proof and were judged to have no real recurrence/residual tumor based on the absence of detectable plasma EB virus DNA and subjective judgment. These 5 patients have remained well after an interval of 38-121 months without anti-cancer treatments.Image-based diagnosis of residual or recurrent nasopharyngeal carcinoma may be unreliable. False positivity, the "phantom tumor phenomenon", is not uncommon in post-radiotherapy MRI. This is particularly true if the images show extensive skull base involvement at 5 years or more after completion of radiotherapy. MRI findings compatible with NPC features must be treated as a real threat until proved otherwise. However, the balance between under- and over-diagnosis must be carefully sought. Without a pathological confirmation, the diagnosis of residual or recurrent NPC must be made taking into account physical examination results, endoscopic findings and Epstein-Barr virus viral load. A subjective medical judgment is needed based on clinical and laboratory data and the unique anatomic complexities of the nasopharynx.

Role and limitations of the geometric mean method regarding head rotation in salivary gland scintigraphy: a phantom study.

To investigate the possible influence of head rotation on the results of salivary gland scintigraphy, a phantom study was designed to simulate clinical salivary gland scintigraphy. The quantitative accuracy of regional activity counts was compared for two data acquisition methods involving head rotation: (i) an anterior planar projection-only (ANT) method and (ii) a geometric mean (GM) method using both the anterior and posterior planar projections. The roles and limitations of the GM and ANT methods when used at different head rotation angles were examined. Parallel planar projections of a head phantom with four salivary gland simulators, containing 3.7 MBq 99mTc-sodium pertechnetate, at various rotational settings were acquired using a dual-head gamma camera. The difference between the standard activity counts (no phantom rotation) and the activity counts affected by the phantom rotation was calculated and defined as the rotational bias that decreased the accuracy of activity quantification. For small-angle rotation (≤10°), use of the GM method decreased the bias for all salivary gland simulators. In contrast, the bias of large-angle rotation (>10°) between four salivary gland simulators became conspicuous and complex in both methods. This bias may reflect different attenuation effects caused by displacement of the structures. Our data suggest that the GM method can be used when the head rotation angle is small (≤10°); however, when the head rotation angle is >10°, the non-negligible influence of head rotation should be considered during image acquisition.

Paralytic ileus as the presenting symptom for Guillain-Barré syndrome: a case report.

Guillain-Barré syndrome (GBS) is an acute neuroimmunological disorder characterized by rapidly ascending symmetrical limb weakness, areflexia, and sensory deficits. Approximately 65% of patients with GBS present with autonomic dysfunction, which commonly occurs in advanced stages. However, paralytic ileus, a sign of gastrointestinal dysautonomia, is rare as the presenting feature in GBS before motor weakness becomes evident. We report the case of a 54-year-old man admitted to the Emergency Department with paralytic ileus as the prodromal feature in early-stage GBS. Total parenteral feeding and prokinetic use were initiated, but no clinical improvement was observed. The patient showed rapid progression to quadriplegia, which was ultimately determined to be respiratory muscle failure requiring mechanical ventilation and intensive care unit admission. He underwent 5 days of intravenous immunoglobulin therapy and muscle strength was partially improved thereafter. However, the patient's enteral nutritional support was undesirable because of persistent poor gastric emptying complicated by fungemia and profound sepsis throughout the hospital course. Finally, he died 1 month after admission. Ignorance of this unusual prodrome to GBS could result in delayed treatment, along with potential progression to life-threatening events. Early recognition of GBS and prompt immunotherapy are critical for reducing morbidity and mortality.