Xiaoqing Zhuang

Background: Pulmonary lesions affect a large population globally, posing huge challenges in clinical management and public healthcare. Functional imaging-based diagnosis facilitates the classification and treatment planning for pulmonary lesions. [ ¹⁸ F]FDG PET/CT is a valuable tool for evaluating pulmonary lesions, but it is limited by false-positive uptake in inflammatory processes. Although quantitative kinetic analysis can improve diagnostic specificity, long dynamic acquisitions pose practical challenges in clinical settings and compromise patient comfort. This study evaluated an efficient and clinically practical protocol combining a 10-min dynamic scan with two-phase static scanning to improve diagnostic accuracy. Results: Forty patients with pulmonary lesions confirmed by histopathology (28 malignant, 12 non-malignant) were included in the analysis. Kinetic parameters were derived from time-activity curves generated by integrating dynamic and static data points using different compartment models with image-derived input functions. Semi-quantitative parameters, including maximum standardized uptake value (SUV _max ), tumor-to-blood standard uptake ratio (SUR) from the early static scan, and delayed SUV _max and delayed SUR from the delayed static scan, were also calculated and assessed. Malignant lesions showed significantly higher net influx rates (K _i ) calculated from Patlak model compared with non-malignant lesions ( P = 0.023). The receiver operating characteristic (ROC) curve analysis for K _i yielded an area under the curve (AUC) of 0.729. Both SUR from the standard static scan ( P = 0.045, AUC = 0.702) and delayed SUR from the 2.5-h static scan ( P = 0.029, AUC = 0.720) were significantly higher in malignant lesions and demonstrated significant diagnostic accuracy. Standard SUV _max , and delayed SUV _max did not show significant differences between groups. Conclusions: The combined 10-min dynamic and two-phase static [ ¹⁸ F]FDG PET/CT protocol may be feasible in selected centers with optimized scheduling. When applicable, this method allows derivation of the net influx rate K _i from Patlak graphical analysis as well as the easily calculated semi-quantitative parameters SUR and delayed SUR, all of which demonstrate significant diagnostic value for differentiating malignant from non-malignant pulmonary lesions, outperforming conventional SUV _max .

Background: Inflammation and vascular calcification are risk factors for cardiovascular disease, but their relationship is still under investigation. This longitudinal in vivo study aimed to monitor inflammation and calcification during the formation of atherosclerotic plaques in apolipoprotein E knockout (ApoE^−/−) rats by ¹⁸F-fluorodeoxyglucose (¹⁸F-FDG) and ¹⁸F-sodium fluoride (¹⁸F-NaF) positron emission tomography/computed tomography (PET/CT). Methods: In the ApoE group, male ApoE^−/− rats were fed a high-fat Western diet from 13 weeks of age, and in the normal group, male SD rats of the same age were fed a normal diet. A longitudinal PET/CT study using ¹⁸F-FDG and ¹⁸F-NaF was performed at 12, 27, and 46 weeks of age. T1-weighted magnetic resonance imaging (MRI) was used as an atlas template, and the uptake of the tracers in the cardiovascular system was analyzed based on atlas 3D geometry volumes-of-interest (VOIs). After the PET/CT study, pathological and immunohistochemical examinations were performed on the corresponding lesions. Results: The body weight and plasma cholesterol levels of the ApoE^−/− rats increased with time, and at each time point, significantly higher body weight and plasma cholesterol levels were observed in the ApoE^−/− rats than in the normal rats. PET/CT showed that in ApoE^−/− rats, the uptake of ¹⁸F-FDG was found in the aortic arch, while the uptake of ¹⁸F-NaF was found in pulmonary arteries. The uptake of the two tracers in the ApoE group increased with time. Extensive early stage of atherosclerotic plaques, with high expression of CD68 and alizarin red, were observed in pulmonary arteries. However, only a thickened intima with very high expression of hypoxia-inducible factor-1 alpha (HIF-1α) was seen in the aortic arch. Conclusions: In ApoE^−/− rats fed a high-fat Western diet, early atherosclerotic lesions developed in the pulmonary arteries; however, ¹⁸F-FDG failed to accumulate in these lesions but to accumulate in the aortic arch with only neointimal hyperplasia and significantly high expression of hypoxia.

Oxidative stress is a hallmark of secondary injury associated with spinal cord injury. Identifying stable and specific oxidative biomarkers is of important significance for studying spinal cord injury-associated secondary injury. Mature erythrocytes do not contain nuclei and mitochondria and cannot be transcribed and translated. Therefore, mature erythrocytes are highly sensitive to oxidative stress and may become a valuable biomarker. In the present study, we revealed the proteome dynamics of protein expression in erythrocytes of beagle dogs in the acute and subacute phases of spinal cord injury using mass spectrometry-based approaches. We found 26 proteins that were differentially expressed in the acute (0–3 days) and subacute (7–21 days) phases of spinal cord injury. Bioinformatics analysis revealed that these differentially expressed proteins were involved in glutathione metabolism, lipid metabolism, and pentose phosphate and other oxidative stress pathways. Western blot assays validated the differential expression of glutathione synthetase, transaldolase, and myeloperoxidase. This result was consistent with mass spectrometry results, suggesting that erythrocytes can be used as a novel sample source of biological markers of oxidative stress in spinal cord injury. Glutathione synthetase, transaldolase, and myeloperoxidase sourced from erythrocytes are potential biomarkers of oxidative stress after spinal cord injury. This study was approved by the Experimental Animal Centre of Ningxia Medical University, China (approval No. 2017-073) on February 13, 2017.

Rationale: Olfactory ensheathing cell (OEC) transplantation has emerged as a promising therapy for spinal cord injury (SCI) repair. In the present study, we explored the possible mechanisms of OECs transplantation underlying neuroinflammation modulation.

Traumatic spinal cord injury (SCI) is a devastating neurological disease for which an accurate, cost-effective prediction of motor function recovery is in pressing need. A plethora of neurochemical changes involved in the pathophysiological process of SCI may serve as a new source of biomarkers for patient outcomes. Five dogs were included in this study. We characterized the plasma cytokine profiles in acute phase (0, 1, and 3 days after SCI) and subacute phase (7, 14, and 21 days after SCI) with microarray analysis. The motor function recovery following SCI was monitored by Olby scores. The expression level of differentially expressed proteins (DEPs) was measured with enzyme-linked immunosorbent assay (ELISA). Then, correlations with the Olby scores and receiver operating characteristic curve (ROC) analysis were performed. We identified 12 DEPs including 10 pro-inflammatory and 2 anti-inflammatory cytokines during the 21-day study period. Among those, the expression levels of erythropoietin (EPO), IL-17A, and IFNγ significantly correlated with the Olby scores withR²values of 0.870, 0.740, and 0.616, respectively. The results of the ROC analysis suggested that plasma EPO, IL-17A, and IFNγ exhibited a significant predictive power with an area under the curve (AUC) of 0.656, 0.848, and 0.800 for EPO, IL-17A, and IFNγ, respectively. Our results provide a longitudinal description of the changes in plasma cytokine expression in the acute and subacute stages of canine SCI. These data reveal novel panels of inflammation-related cytokines which have the potential to be evaluated as biomarkers for predicting motor function prognosis after SCI.

Cellular transplantation strategies utilizing intraspinal or intrathecal olfactory ensheathing cells (OECs) have been reported as beneficial for spinal cord injury (SCI). However, there are many disadvantages of these methods, including additional trauma to the spinal cord parenchyma and technical challenges. Therefore, we investigated the feasibility and potential benefits of intravenous transplantation of OECs in a rat hemisection SCI model. OECs derived from olfactory bulb tissue were labeled with quantum dots (QDs), and their biodistribution after intravenous transplantation was tracked using a fluorescence imaging system. Accumulation of the transplanted OECs was observed in the injured spinal cord within 10 min, peaked at seven days after cell transplantation, and decreased gradually thereafter. This time window corresponded to the blood–spinal cord barrier (BSCB) opening time, which was quantitated with the Evans blue leakage assay. Using immunohistochemistry, we examined neuronal growth (GAP-43), remyelination (MBP), and microglia (Iba-1) reactions at the lesion site. Motor function recovery was also measured using a classic open field test (Basso, Beattie and Bresnahan score). Compared with the group injected only with QDs, the rats that received OEC transplantation exhibited a prominent reduction in inflammatory responses, increased neurogenesis and remyelination, and significant improvement in motor function. We suggest that intravenous injection could also be an effective method for delivering OECs and improving functional outcomes after SCI. Moreover, the time course of BSCB disruption provides a clinically relevant therapeutic window for cell-based intervention.

To analyze erythropoietin receptor (EpoR) status in tumors, recombinant human erythropoietin (rHuEpo) was labeled with ^99mTc by ^99mTc‐centered 1‐pot synthesis, resulting in high radiochemical purity, stability, and biological activity. Both in vitro cell culture experiments and biodistribution studies of normal rats demonstrated successful EpoR targeting. The biodistribution of labeled rHuEpo in a NCI‐H1975 xenograft model showed tumor accumulation (tumor‐to‐muscle ratio, 4.27 ± 1.77), confirming the expression of active EpoR in tumors. Thus, as a novel single positron emission computerized tomography tracer for the imaging of EpoR expression in vivo, ^99mTc‐rHuEpo is effective for exploring the role of EpoR in cancer growth, metastasis and angiogenesis.

A 59-year-old man presented cough, chest pain, and shortness of breath for 2 weeks and fever for 4 days. A contrast chest CT revealed a large right pulmonary artery filling defect, suggestive of pulmonary embolism that failed to respond to anticoagulation therapy. FDG PET/CT was performed to evaluate possible malignancy, which revealed intense activity in the right main pulmonary artery without any extrathoracic abnormality. The ratio of the SUVmax of this lesion to the liver was significantly increased in the delayed PET images. The pathological examination demonstrated primary pulmonary artery sarcoma.