Myeloid-derived MIF drives RIPK1-mediated cerebromicrovascular endothelial cell death to exacerbate ischemic brain injury.

Macrophage migration inhibitory factor (MIF) is a multifaced protein that plays important roles in multiple inflammatory conditions. However, the role of MIF in endothelial cell (EC) death under inflammatory condition remains largely unknown. Here we show that MIF actively promotes receptor-interacting protein kinase 1 (RIPK1)-mediated cell death under oxygen-glucose deprivation condition. MIF expression is induced by surgical trauma in peripheral myeloid cells both in perioperative humans and mice. We demonstrate that MIF-loaded myeloid cells induced by peripheral surgery adhere to the brain ECs after distal middle cerebral artery occlusion (dMCAO) and exacerbate the blood-brain barrier (BBB) disruption. Genetic depletion of myeloid-derived MIF in perioperative ischemic stroke (PIS) mice with MCAO following a surgical insult leads to significant reduction in ECs apoptosis and necroptosis and the associated BBB disruption. The adoptive transfer of peripheral blood mononuclear cells (PBMC) from surgical MIFΔLyz2 mice to wild-type (WT) MCAO mice also shows reduced ECs apoptosis and necroptosis compared to the transfer of PBMC from surgical MIFf  l/f  l mice to MCAO recipients. The genetic inhibition of RIPK1 also attenuates BBB disruption and ECs death compared to that of WT mice in PIS. The administration of MIF inhibitor (ISO-1) and RIPK1 inhibitor (Nec-1s) can both reduce the brain EC death and neurological deficits following PIS. We conclude that myeloid-derived MIF promotes ECs apoptosis and necroptosis through RIPK1 kinase-dependent pathway. The above findings may provide insights into the mechanism as how peripheral inflammation promotes the pathology in central nervous system.

Correlation Between Bioelectrical Impedance Analysis and Chest CT-Measured Erector Spinae Muscle Area: A Cross-Sectional Study.

Background: Skeletal muscle mass (SMM) plays an important part in diverse health and disease states. Bioelectrical impedance analysis (BIA) and computed tomography (CT) are available for its assessment. However, muscle mass assessed by BIA may be influenced by multiple factors. The erector spinae muscle area (ESA) on chest CT is recently presumed to be representative of SMM. This study aimed to derive BIA from the ESA and evaluate the magnitude of association (between ESA measured from chest CT) and BIA. Methods: Subjects hospitalized for health checkups between December 2020 and December 2021, having undergone both BIA (50 kHz, 0.8 mA) and chest CT, were included. ESA was quantified at the level of the 12th thoracic vertebra (T12-ESA) by a standardized semi-automated segmentation algorithm. Low SMM was defined using the Asian Working Group for Sarcopenia criteria. The association between T12-ESA and BIA was then evaluated. Stratified analyses by sex and BMI were also performed. Results: Among 606 included subjects (59.7 ± 16.6 years, 63.5% male), 110 (18.2%) had low SMM. BMI in low and normal SMM groups was 20.1 and 24.7 kg/m2, respectively. Current smoking, drinking, chronic obstructive pulmonary disease, and chronic renal dysfunction were more frequently seen in the low SMM group than in the normal SMM group. The final regression model included T12-ESA, weight, BMI, and age, and had an adjusted R2 of 0.806 with BIA. In the validation group, the correlation between T12-ESA-derived BIA and BIA remained high (Pearson correlation = 0.899). Stratified analysis disclosed a stronger correlation between T12-ESA and BIA in male subjects than in female subjects (adjusted R2 = 0.790 vs. adjusted R2 = 0.711, p < 0.05), and a better correlation was observed in obese (BMI ≥ 30 kg/m2) compared with underweight (BMI < 18.5 kg/m2) subjects (adjusted R2 = 0.852 vs. adjusted R2 = 0.723, p < 0.05). Additional analysis revealed a significant correlation between T12-ESA and skeletal muscle cross-sectional area at the 3rd lumbar vertebra (L3-CSA) (adjusted R2 = 0.935, p < 0.001). Conclusions: CT-based assessment of ESA at the T12 level is feasible and correlated well with BIA, especially in male subjects and obese subjects.

Analysis on risk factors of lung cancer complicated with pulmonary embolism.

INTRODUCTION: Pulmonary embolism (PE) is a potentially fatal complication and its morbidity together with fatalness will further increase when in patients with malignant tumors. Fast and accurate early diagnosis of PE thus seems considerably important. OBJECTIVE: To explore the risk factors of lung cancer complicated with PE. MATERIALS AND METHODS: A retrospective cohort study consisted of 40 lung cancer patients with PE (PE group) and 60 lung cancer patients without PE (non-PE group) were analyzed. RESULTS: The white blood cell (WBC) count, D-dimer and low-density lipoprotein (LDL) were higher in PE group than those in non-PE group (P < 0.05), whereas the arterial partial pressure of oxygen (PaO2 ) in PE group was lower than that in non-PE group (P < 0.05). Carcinoembryonic antigen (CEA) level between two groups also exhibited statistical difference (P < 0.05). Those lung adenocarcinoma patients with stages III and IV tumor, coupled with deep venous thrombosis (DVT), having experienced bevacizumab treatment or platinum-based chemotherapy more likely suffered from PE (P < 0.05). The multivariate analysis revealed that high D-dimer, chemotherapy, DVT, stages III to IV, adenocarcinoma were independent risk factors associated with PE (P < 0.05). The overall survival time of patients in case group was significantly shorter than that in the control group with a median survival duration being 10.5 months (95%CI, 8.95-12.05) and 16.8 months (95%CI, 14.62-18.98), respectively, (P < 0.01). CONCLUSIONS: High D-dimer, chemotherapy, DVT, stages III to IV and adenocarcinoma might have a positive correlation with PE, meanwhile, PE always predicted a poor prognosis in lung cancer patients.

Stroke Exacerbates Cancer Progression by Upregulating LCN2 in PMN-MDSC.

Acute ischemic stroke (AIS) is common in patients with cancer, and mounting clinical evidence suggests that it may shorten the survival of cancer patients. But how stroke affects the progression of cancer remains unclear. We inoculated B16 tumor cells (2 × 105) subcutaneously before distal middle cerebral artery occlusion (dMCAO) or sham surgery in C57BL/6 mice and found that compared to sham operated mice, dMCAO mice developed significantly increased tumor volume and were accompanied by lower survival rate. To explore the underlying mechanism, we performed RNA-sequencing analysis of the tumor tissue from mice with or without stroke and found prominent upregulation of lipocalin 2 (LCN2) in the tumor from stroke mice compared to those from sham mice. Using quantitative reverse transcription-PCR, we confirmed increased mRNA expression of LCN2 as well as anti-inflammatory cytokines-Arg1, IL-10, and decreased mRNA level of pro-inflammatory cytokines-IL-6, IL-23 in the tumor of cancer-bearing stroke mice. Both immunofluorescence staining and flow cytometry analysis revealed that increased expression of LCN2 was mainly derived from the polymorphonuclear myeloid derived suppressor cells (PMN-MDSCs) in the tumor. We also found that stroke reduced the PMN-MDSCs in the peripheral blood, but increased PMN-MDSCs in the tumor of the cancer-bearing mice after stroke. In conclusion, cerebral ischemic stroke may exacerbate cancer progression by increasing LCN2 expression in PMN-MDSCs, which turns out to be a promising therapeutic target to suppress cancer progression after ischemic stroke.

Assessment of stereotactic radiosurgery treatment response for brain metastases using MRI based diffusion index.

INTRODUCTION: To investigate the clinical predictive values of the apparent diffusion coefficient (ADC) as a biomarker in radiation response of brain metastases. METHOD: Forty-one patients with brain metastases treated with stereotactic radiosurgery (SRS) were imaged at baseline, one month post SRS, and six months post SRS using diffusion weighted MRI. The mean of ADC for metastases and tumor volume was calculated. A diffusion index (DI) was generated using the sum of 1/ADC among all the voxels in a tumor. Tumor response status was determined by lesion volume measured at six month post-SRS, or the last available follow-up MRI. Logistic regression analysis was used to account for factors associated with tumor response at baseline and one month post SRS. RESULTS: A higher ADC mean distinguished responders from non-responders only at six month post SRS (p < 0.05). However, a lower DI distinguished a responder from non-responders on the baseline, one month post SRS and six months post SRS, indicating better diagnostic performance of the DI with regard to a non-invasive biomarker in monitoring SRS treatment response. A multivariate logistic regression analysis identified the DI as a predictor of tumor response at baseline and one month post SRS (p = 0.002 and p = 0.001, respectively). However, logistic regression analysis identified the ADC mean as a predictor of tumor response only at six months post SRS (p = 0.019). CONCLUSION: Our results support the hypothesis that ADC and tumor volume generated DT at baseline, one month and six months post SRS may be a promising biomarker predicting brain metastases' response. Specifically, a lower DI at baseline and one month distinguished responders from non-responders.

Apparent diffusion coefficient measurement in glioma: Influence of region-of-interest determination methods on apparent diffusion coefficient values, interobserver variability, time efficiency, and diagnostic ability.

PURPOSE: To compare four methods of region-of-interest (ROI) placement for apparent diffusion coefficient (ADC) measurements in distinguishing low-grade gliomas (LGGs) from high-grade gliomas (HGGs). MATERIALS AND METHODS: Two independent readers measured ADC parameters using four ROI methods (single-slice [single-round, five-round and freehand] and whole-volume) on 43 patients (20 LGGs, 23 HGGs) who had undergone 3.0 Tesla diffusion-weighted imaging and time required for each method of ADC measurements was recorded. Intraclass correlation coefficients (ICCs) were used to assess interobserver variability of ADC measurements. Mean and minimum ADC values and time required were compared using paired Student's t-tests. All ADC parameters (mean/minimum ADC values of three single-slice methods, mean/minimum/standard deviation/skewness/kurtosis/the10th and 25th percentiles/median/maximum of whole-volume method) were correlated with tumor grade (low versus high) by unpaired Student's t-tests. Discriminative ability was determined by receiver operating characteristic curves. RESULTS: All ADC measurements except minimum, skewness, and kurtosis of whole-volume ROI differed significantly between LGGs and HGGs (all P < 0.05). Mean ADC value of single-round ROI had the highest effect size (0.72) and the greatest areas under the curve (0.872). Three single-slice methods had good to excellent ICCs (0.67-0.89) and the whole-volume method fair to excellent ICCs (0.32-0.96). Minimum ADC values differed significantly between whole-volume and single-round ROI (P = 0.003) and, between whole-volume and five-round ROI (P = 0.001). The whole-volume method took significantly longer than all single-slice methods (all P < 0.001). CONCLUSION: ADC measurements are influenced by ROI determination methods. Whole-volume histogram analysis did not yield better results than single-slice methods and took longer. Mean ADC value derived from single-round ROI is the most optimal parameter for differentiating LGGs from HGGs. LEVEL OF EVIDENCE: 3 J. Magn. Reson. Imaging 2017;45:722-730.

Social behavioral testing and brain magnetic resonance imaging in chicks exposed to mobile phone radiation during development.

BACKGROUND: The potential adverse effect of mobile phone radiation is currently an area of great concern in the field of public health. In the present study, we aimed to investigate the effect of mobile phone radiation (900 MHz radiofrequency) during hatching on postnatal social behaviors in chicks, as well as the effect on brain size and structural maturity estimated using 3.0 T magnetic resonance imaging. At day 4 of incubation, 76 normally developing chick embryos were divided into the control group (n = 39) and the radiation group (n = 37). Eggs in the radiation group were exposed to mobile phone radiation for 10 h each day from day 4 to 19 of incubation. Behavioral tests were performed 4 days after hatching. T2-weighted MR imaging and diffusion tensor imaging (DTI) were subsequently performed. The size of different brain subdivisions (telencephalon, optic lobe, brain stem, and cerebellum) and corresponding DTI parameters were measured. The Chi-square test and the student's t test were used for statistical analysis. P < 0.05 was considered statistically significant. RESULTS: Compared with controls, chicks in the radiation group showed significantly slower aggregation responses (14.87 ± 10.06 vs. 7.48 ± 4.31 s, respectively; P < 0.05), lower belongingness (23.71 ± 8.72 vs. 11.45 ± 6.53 s, respectively; P < 0.05), and weaker vocalization (53.23 ± 8.60 vs. 60.01 ± 10.45 dB/30 s, respectively; P < 0.05). No significant differences were found between the radiation and control group for brain size and structural maturity, except for cerebellum size, which was significantly smaller in the radiation group (28.40 ± 1.95 vs. 29.95 ± 1.41 cm(2), P < 0.05). The hatching and heteroplasia rates were also calculated and no significant difference was found between the two groups. CONCLUSIONS: Mobile phone radiation exposure during chick embryogenesis impaired social behaviors after hatching and possibly induced cerebellar retardation. This indicates potential adverse effects of mobile phone radiation on brain development.

Usefulness of dual-energy computed tomography imaging in the differential diagnosis of sellar meningiomas and pituitary adenomas: preliminary report.

OBJECTIVE: To quantitatively assess the imaging characteristics of sellar lesion in dual-energy computed tomography (CT) imaging for differentiation of sellar meningiomas and pituitary adenomas during the arterial phase (AP) and venous phase (VP). MATERIALS AND METHODS: 51 patients with sellar/parasellar tumors (33 macroadenomas and 18 meningiomas) were examined with CT spectral imaging during the AP and the VP. Iodine concentrations were derived from iodine-based material-decomposition CT images and normalized to the iodine concentration in the aorta. The difference in Normalized iodine concentrations (NICs), HU curve slope (λHU), and mean CT values of lesions between the AP and VP were calculated. The two-sample t test was performed to compare quantitative parameters between sellar meningiomas and pituitary adenomas. RESULTS: NICs, λHU, and mean CT values in patients with sellar meningiomas differed significantly from those in patients with pituitary adenomas: Mean NICs were 43.52 mg/mL±1.35 versus 9.23 mg/mL ±2.44, respectively, during the AP and 52.13 mg/mL ±1.04 versus 24.37 mg/mL ±2.23 respectively, during the VP. λHU were -3.03±3.42 versus -0.53±0.23, respectively, during the AP and -2.96±0.41 versus -0.47±0.25, respectively, during the VP. Mean CT values were 193.63±2.08 versus 63.98±2.85, respectively, during the AP and 203.98±0.18 versus 77.66±0.91, respectively, during the VP. The combination of NIC and Mean CT value during VP had highest sensitivity (90.9%) and specificity (100%) among all phases. CONCLUSION: Quantitative dual-energy CT imaging has promising potential for diagnostic differentiation of sellar meningiomas and pituitary adenomas.