Knockdown of EIF2AK2-OAS1 axis reduces ATP production inducing AMPK phosphorylation to inhibit the malignant behavior of gastric cancer cells.

Energy metabolism has always been a hot topic in cancer progression and targeted therapy, and exploring the role of genes in energy metabolic pathways in cancer cells has become key to address this issue. Eukaryotic translation initiation factor 2α kinase 2 (EIF2AK2) plays regulatory roles in cancer and disorders of energy metabolism. Indeed, the role of EIF2AK2 in energy metabolism has been underestimated. The aim of this study is to reveal the expression specificity of EIF2AK2 in gastric cancer (GC) progression and metastasis, and to demonstrate the role of EIF2AK2 in energy metabolism, cytoskeleton, proliferation, death and metastasis pathways in GC cells. Mechanistically, EIF2AK2 overexpression promoted cytoskeleton remodeling and ATP production, mediated cell proliferation and metastasis, upregulated OAS1 expression, decreases p-AMPK expression and inhibited apoptosis in GC cells. Conversely, knockdown of EIF2AK2 resulted in the opposite effect. However, overexpression of OAS1 mediated the upregulation of mitochondrial membrane potential and promoted ATP production and NAD+/NADH ratio, but knockdown of OAS1 inhibited the above effects. In addition, knockdown of OAS1 had no effect on EIF2AK2 expression, but inhibited AMPK and upregulated p-AMPK expression. In conclusion, our study identified EIF2AK2 and OAS1 as previously undescribed regulators of energy metabolism in GC cells. We hypothesized that EIF2AK2-OAS1 axis may regulate energy metabolism and inhibit cellular malignant behavior in cancer cells by affecting ATP production to induce AMPK phosphorylation, suggesting EIF2AK2 as a potential therapeutic target for cancer cell progression.

Value of Magnetic Resonance T1 Mapping in Evaluating the Early Response to Treatment for Rheumatoid Arthritis.

BACKGROUND: Rheumatoid Arthritis Magnetic Resonance Imaging Score (RAMRIS) is usually used for the semi-quantitative evaluation of joint changes in Rheumatoid Arthritis (RA). However, this method cannot evaluate early changes in bone marrow edema (BME). OBJECTIVE: To determine whether T1 mapping of wrist BME predicts early treatment response in RA. METHODS: This study prospectively enrolled 48 RA patients administered oral anti-rheumatic drugs. MRI of the most severely affected wrist was performed before and after 4 (48 patients) and 8 weeks of treatment (38 patients). Mean T1 values of BME in the lunate, triangular, and capitate bones; RAMRIS for each wrist; Erythrocyte-Sedimentation Rate (ESR); and 28-joint Disease Activity Score (DAS28)-ESR score were analyzed. Patients were divided into responders (4 weeks, 30 patients; 8 weeks, 32 patients) and non-responders (4 weeks, 18 patients; 8 weeks, 6 patients), according to EULAR response criteria. Receiver operating characteristic (ROC) curves were used to evaluate the efficacy of T1 values. RESULTS: ESR and DAS28-ESR were not correlated with T1 value and RAMRIS at each examination (P > 0.05). Changes in T1 value and DAS28-ESR relative to the baseline were moderately positively correlated with each other at 4 and 8 weeks (r = 0.555 and 0.527, respectively; P < 0.05). At 4 weeks, the change and rate of change in T1 value significantly differed between responders and non-responders (-85.63 vs. -19.92 ms; -12.89% vs. -2.81%; P < 0.05). The optimal threshold of the rate of change in T1 value at 4 weeks for predicting treatment response was -5.32% (area under the ROC curve, 0.833; sensitivity, 0.900; specificity, 0.667). CONCLUSION: T1 mapping provides a new imaging method for monitoring RA lesions; changes in wrist BME T1 values reflect early treatment response.

CT and MRI Findings of Solitary Extramedullary Plasmacytoma: A Series of Ten Case Reports and Review of Literature.

OBJECTIVE: The study aimed to analyze computed tomography and magnetic resonance imaging features of patients with solitary extramedullary plasmacytoma. METHODS: Ten cases with solitary extramedullary plasmacytoma were included in this study. CT and MRI features of solitary extramedullary plasmacytoma were retrospectively analyzed. RESULTS: This study included both males (n = 8) and females (n = 2), with a median age of 48 (range 21-72 years old). The organs or anatomical structures involved were nasopharynx (n = 3), orbit (n = 1), left tentorium (n = 1), nasal cavity and meatus (n = 2), small intestine and mesentery (n = 1), as well as posterior thoracic wall (n = 2). The median maximum diameter of the tumors was 3.2 cm (range 0.8- 15.2 cm). The tumor shapes were round (n = 7), stripped (n = 1), irregular (n = 1), and nodular (n = 1). The margin of the tumors was well-defined (n = 7) and partially well-defined (n = 3). There were 3 cases with bone destruction and 1 with a tissue invasion adjacent to the tumor, calcification (n = 1), and cystic degeneration (n = 2). Enlarged tumoral vessels (n = 4) could also be observed. The CT attenuation and MR signal intensity of tumors were heterogeneous (n = 4) and homogenous (n = 6). After the injection of the contrast agent, marked (n = 5), mild (n = 1), mild to moderate (n = 1), and delayed enhancement (n = 1) could be observed. CONCLUSION: A well-defined homogeneous solitary mass occurring at the head and neck with a marked enhancement, an adjacent tissue invasion, enlarged tumoral vessels, and bone destruction can indicate the diagnosis of solitary extramedullary plasmacytoma.

Radiomics in Addition to Computed Tomography-Based Body Composition Nomogram May Improve the Prediction of Postoperative Complications in Gastric Cancer Patients.

OBJECTIVES: The study aimed to determine the impact of computed tomography (CT)-based body composition and radiomics nomogram on the prediction of postoperative complications in gastric cancer. METHODS: The clinical data of 457 individuals with surgically confirmed gastric cancer, 320 patients in the training cohort (TC) and 137 patients in the validation cohort (VC), were retrospectively analyzed. Body composition data were measured using CT. Postoperative complications were graded using the Clavien-Dindo system. Dedicated radiomics prototype software was used to segment lesions and extract characteristics from preoperative portal venous-phase CT images. Clinical, radiomics, and combined models were developed using logistic regression analysis. Model performance was evaluated using the area under the curve (AUC) of receiver operating characteristic curve, and the prediction ability of the optimal model was evaluated using calibration curves and decision curve analysis (DCA). RESULTS: Nutritional Risk Screening 2002 (NRS2002) score, sarcopenia, and blood loss were independent predictors of postoperative complications in gastric cancer. A radiomics signature was created using 19 conserved radiomics features. The nomogram based on both the clinical model and radiomics signature showed the greatest predictive performance, with AUCs of 0.763 (95% confidence interval [CI], 0.708-0.817) and 0.748 (95% CI: 0.667-0.818) in the TC and VC, respectively. The calibration curve and DCA revealed that the nomogram was beneficial in clinical practice for the preoperative prediction of postoperative complications. CONCLUSIONS: The combined model consisting of NRS2002 score, sarcopenia, blood loss, and a radiomics signature holds potential application value for the individualized prediction of postoperative complications in gastric cancer patients.

Comparison of clinical-computed tomography model with 2D and 3D radiomics models to predict occult peritoneal metastases in advanced gastric cancer.

PURPOSE: To compare the ability of a clinical-computed tomography (CT) model vs. 2D and 3D radiomics models for predicting occult peritoneal metastasis (PM) in patients with advanced gastric cancer (AGC). METHODS: In this retrospective study, we included 49 patients with occult PM and 49 control patients (without PM) who underwent preoperative CT and subsequent surgery between January 2016 and December 2018. Clinical information and CT semantic features were collected, and CT radiomics features were extracted. A predictive clinical-CT model was created using multivariate logistic regression. The least absolute shrinkage and selection operator algorithm and logistic regression were used for constructing 2D and 3D radiomics models. These models were validated with an external cohort (n = 30). Receiver operating characteristics curve with area under the curve (AUC), sensitivity, and specificity were used to evaluate predictive performance. RESULTS: Tumor size, mild ascites, and serum CA125 were independent factors predictive of occult PM. The clinical-CT model of these independent factors showed better diagnostic performance than 2D and 3D radiomics models. In the external validation cohort, the AUCs of different models were as follows-clinical-CT model: 0.853 (sensitivity, 66.7%; specificity, 93.3%); 2D radiomics model: 0.622 (sensitivity, 80.0%; specificity, 46.7%); and 3D radiomics model: 0.676 (sensitivity, 60.0%; specificity, 86.0%). The clinical-CT model nomogram showed good clinical predictive efficiency to assess occult PM. CONCLUSION: The clinical-CT model was better than the radiomics models in predicting occult PM in AGC.

Efficacy of Diffusion-Weighted Imaging in Neoadjuvant Chemotherapy for Osteosarcoma: A Systematic Review and Meta-Analysis.

RATIONALE AND OBJECTIVES: Diffusion-weighted imaging (DWI) is a noninvasive imaging technique that reflects the diffusion movement of water molecules through apparent diffusion coefficient (ADC) values. The role of DWI in predicting the histological response to neoadjuvant chemotherapy in osteosarcoma is being increasingly researched, and a systematic review and meta-analysis of this topic is urgently required to help determine the potential diagnostic value of DWI. MATERIALS AND METHODS: The present meta-analysis included 13 studies (303 patients). We divided the target population into good responders and poor responders based on tumor necrosis on histological biopsy (≥90%, good responders). The mean ADC values and ADC ratio were extracted and/or calculated for the two groups. RESULTS: The mean difference in ADC values before and after neoadjuvant chemotherapy was significantly higher in good responders than in poor responders (mean difference, 0.33; 95% confidence interval [CI], 0.18-0.49; p< 0.0001), and significant heterogeneity was present among the 10 studies that reported these values (I2 = 66%, p< 0.05). The ADC ratio was also significantly higher in good responders than in poor responders (mean difference, 28.34; 95% CI, 1.83-54.85; p = 0.04), and significant heterogeneity in ADC ratio was present among 7 studies (I2 = 97%, p< 0.05). CONCLUSION: The mean differences in ADC values and ADC ratios before and after neoadjuvant chemotherapy for osteosarcoma were significantly higher in good responders than in poor responders.

Quantification of bone marrow edema in rheumatoid arthritis by using high-speed T2-corrected multiecho acquisition of 1H magnetic resonance spectroscopy: a feasibility study.

OBJECTIVE: To determine whether high-speed T2-corrected multiecho (HISTO) sequences can quantify bone marrow edema (BME) in the capitate bone in rheumatoid arthritis (RA), and whether the HISTO fat fraction (FF) reflects therapeutic effectiveness. METHODS: In this prospective study, 25 RA patients (19 women; average age, 45.08 ± 13.48 years) underwent 3.0-T MRI with HISTO at the baseline and after 4, 8, and 12 weeks of treatment. Rheumatoid factor (RF), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), platelet (PLT) count, and 28-joint Disease Activity Score using ESR (DAS28-ESR) were recorded on the day of each MRI examination by a rheumatologist blinded to the MRI findings. In addition, 21 healthy subjects (15 women; age, 49.17 ± 6.56 years) underwent only the HISTO sequence at a single time point. RESULTS: HISTO FF values were significantly higher in the control group (74.5% ± 3.1%; range, 68.6-79.3%) than in the patient group (55.8% ± 17.7%; range, 15.6-79.0%) at the baseline (independent-samples t-test: t = 5.257, P = 0.000). The changes in HISTO FF and DAS28-ESR showed moderate negative correlations with each other at 4, 8, and 12 weeks, and all of them were statistically significant (P < 0.05). As the HISTO FF increased, the DAS28-ESR decreased. CONCLUSION: The HISTO sequence can measure the bone marrow FF of the wrist joint bones in RA patients. The HISTO FF value increased as the DAS28-ESR decreased. The HISTO sequence may help quantify BME in RA and help monitor the effectiveness of RA treatment. Key Points •The HISTO sequence could measure the bone marrow FF of the wrist joint bones. •FF value increased as the DAS28-ESR decreased in RA patients. •The HISTO sequence can monitor the therapeutic effect of RA.

Changes in Regional Brain Homogeneity Induced by Electro-Acupuncture Stimulation at the Baihui Acupoint in Healthy Subjects: A Functional Magnetic Resonance Imaging Study.

INTRODUCTION: According to the Traditional Chinese Medicine theory of acupuncture, Baihui (GV20) is applied to treat neurological and psychiatric disorders. However, the relationships between neural responses and GV20 remain unknown. Thus, the main aim of this study was to examine the brain responses induced by electro-acupuncture stimulation (EAS) at GV20. MATERIALS AND METHODS: Functional magnetic resonance imaging (fMRI) was performed in 33 healthy subjects. Based on the non-repeated event-related (NRER) paradigm, group differences were examined between GV20 and a sham acupoint using the regional homogeneity (ReHo) method. RESULTS: Compared with the sham acupoint, EAS at GV20 induced increased ReHo in regions including the orbital frontal cortex (OFC), middle cingulate cortex (MCC), precentral cortex, and precuneus (preCUN). Decreased ReHo was found in the anterior cingulate cortex (ACC), supplementary motor area (SMA), thalamus, putamen, and cerebellum. CONCLUSIONS: The current findings provide preliminary neuroimaging evidence to indicate that EAS at GV20 could induce a specific pattern of neural responses by analysis of ReHo of brain activity. These findings might improve the understanding of mechanisms of acupuncture stimulation at GV20.

Functional polymorphism -31C/G in the promoter of BIRC5 gene and risk of nasopharyngeal carcinoma among chinese.

BACKGROUND: Baculoviral inhibitor of apoptosis repeat-containing 5 (BIRC5, also called as survivin) is a member of the inhibitor of apoptosis protein (IAP) family, which plays an important role in the occurrence and progression of cancer. Recently, a polymorphism in the promoter of BIRC5, -31C/G (rs9904341), was shown to influence BIRC5 expression. METHODS: We examined whether the -31C/G was related to the risk of developing nasopharyngeal carcinoma (NPC) in a case-control population from Guangxi province in southern China, which consists of 855 patients with NPC and 1036 controls. This polymorphism was genotyped by TaqMan assay. The genetic associations with the occurrence and progression of NPC were estimated by logistic regression. RESULTS: We observed a statistically significant increased occurrence of NPC associated with the CC genotype (odds ratio [OR], 1.40; 95% confidence interval [CI], 1.13-1.73; P=0.0020) compared with the genotypes containing G allele (CG + GG genotype). However, no significant association was observed for the -31C/G with the severity of NPC (as measured by tumor-node-metastasis staging system). CONCLUSION: Our findings suggest that the functional polymorphism -31C/G in the promoter of BIRC5 gene may play a role in mediating the susceptibility to NPC among Chinese.