The clinical value of dual-energy CT imaging in preoperative evaluation of pathological types of gastric cancer.

BACKGROUND: Gastric cancer (GC) is the fifth most common cancer worldwide and the third leading cause of cancer death. Due to the low rate of early diagnosis, most patients are already in the advanced stage and lose the chance of radical surgery. OBJECTIVE: To investigate the clinical value of computed tomography (CT) dual-energy imaging in preoperative evaluation of pathological types of gastric cancer patients. METHODS: 121 patients with gastric cancer were selected. Dual-energy CT imaging was performed on the patients. The CT values of virtual noncontrast (VNC) images and iodine concentration of the lesion were measured, and the standardized iodine concentration ratio was calculated. The iodine concentration, iodine concentration ratio and CT values of VNC images of different pathological types were analyzed and compared. RESULTS: The iodine concentration and iodine concentration ratio of gastric mucinous carcinoma patients in venous phase and parenchymal phase were lower than those of gastric non-mucinous carcinoma patients, and the differences were statistically significant (P< 0.05). The iodine concentration and iodine concentration ratio of patients with mucinous adenocarcinoma in venous phase and parenchymal phase were lower than those of patients with choriocarcinoma, and the differences were statistically significant (P< 0.05). The iodine concentration and iodine concentration ratio of middle and high differentiated adenocarcinoma patients in venous phase and parenchymal phase were lower than those of low differentiated adenocarcinoma patients, and the differences were statistically significant (P< 0.05). However, there was no significant difference in CT values of VNC images among venous, arterial, and parenchymal phases in all pathological types of gastric cancer patients (P> 0.05). CONCLUSION: Dual-energy CT imaging plays an important role in the preoperative evaluation of patients with gastric cancer. The pathological types of gastric cancer are different, and the iodine concentration will change accordingly. Dual-energy CT imaging can effectively evaluate the pathological types of gastric cancer and has high clinical application value.

Regulation of Axon Initial Segment Diameter by COUP-TFI Fine-tunes Action Potential Generation.

The axon initial segment (AIS) is a specialized structure that controls neuronal excitability via action potential (AP) generation. Currently, AIS plasticity with regard to changes in length and location in response to neural activity has been extensively investigated, but how AIS diameter is regulated remains elusive. Here we report that COUP-TFI (chicken ovalbumin upstream promotor-transcription factor 1) is an essential regulator of AIS diameter in both developing and adult mouse neocortex. Either embryonic or adult ablation of COUP-TFI results in reduced AIS diameter and impaired AP generation. Although COUP-TFI ablations in sparse single neurons and in populations of neurons have similar impacts on AIS diameter and AP generation, they strengthen and weaken, respectively, the receiving spontaneous network in mutant neurons. In contrast, overexpression of COUP-TFI in sparse single neurons increases the AIS diameter and facilitates AP generation, but decreases the receiving spontaneous network. Our findings demonstrate that COUP-TFI is indispensable for both the expansion and maintenance of AIS diameter and that AIS diameter fine-tunes action potential generation and synaptic inputs in mammalian cortical neurons.

Imbalance of Excitatory/Inhibitory Neuron Differentiation in Neurodevelopmental Disorders with an NR2F1 Point Mutation.

Recent studies have revealed an essential role for embryonic cortical development in the pathophysiology of neurodevelopmental disorders, including autism spectrum disorder (ASD). However, the genetic basis and underlying mechanisms remain unclear. Here, we generate mutant human embryonic stem cell lines (Mut hESCs) carrying an NR2F1-R112K mutation that has been identified in a patient with ASD features and investigate their neurodevelopmental alterations. Mut hESCs overproduce ventral telencephalic neuron progenitors (ventral NPCs) and underproduce dorsal NPCs, causing the imbalance of excitatory/inhibitory neurons. These alterations can be mainly attributed to the aberrantly activated Hedgehog signaling pathway. Moreover, the corresponding Nr2f1 point-mutant mice display a similar excitatory/inhibitory neuron imbalance and abnormal behaviors. Antagonizing the increased inhibitory synaptic transmission partially alleviates their behavioral deficits. Together, our results suggest that the NR2F1-dependent imbalance of excitatory/inhibitory neuron differentiation caused by the activated Hedgehog pathway is one precursor of neurodevelopmental disorders and may enlighten the therapeutic approaches.

Calcineurin Signaling Mediates Disruption of the Axon Initial Segment Cytoskeleton after Injury.

The axon initial segment (AIS) cytoskeleton undergoes rapid and irreversible disruption prior to cell death after injury, and loss of AIS integrity can produce profound neurological effects on the nervous system. Here we described a previously unrecognized mechanism for ischemia-induced alterations in AIS integrity. We show that in hippocampal CA1 pyramidal neurons Nav1.6 mostly preserves at the AIS after disruption of the cytoskeleton in a mouse model of middle cerebral artery occlusion. Genetic removal of neurofascin-186 leads to rapid disruption of Nav1.6 following injury, indicating that neurofascin is required for Nav1.6 maintenance at the AIS after cytoskeleton collapse. Importantly, calcineurin inhibition with FK506 fully protects AIS integrity and sufficiently prevents impairments of spatial learning and memory from injury. This study provides evidence that calcineurin activation is primarily involved in initiating disassembly of the AIS cytoskeleton and that maintaining AIS integrity is crucial for therapeutic strategies to facilitate recovery from injury.