Resting-state brain plasticity is associated with the severity in cervical spondylotic myelopathy.

OBJECTIVE: To investigate the brain mechanism of non-correspondence between imaging presentations and clinical symptoms in cervical spondylotic myelopathy (CSM) patients and to test the utility of brain imaging biomarkers for predicting prognosis of CSM. METHODS: Forty patients with CSM (22 mild-moderate CSM, 18 severe CSM) and 25 healthy controls (HCs) were recruited for rs-fMRI and cervical spinal cord diffusion tensor imaging (DTI) scans. DTI at the spinal cord (level C2/3) with fractional anisotropy (FA) and degree centrality (DC) were recorded. Then one-way analysis of covariance (ANCOVA) was conducted to detect the group differences in the DC and FA values across the three groups. Pearson correlation analysis was then separately performed between JOA with FA and DC. RESULTS: Among them, degree centrality value of left middle temporal gyrus exhibited a progressive increase in CSM groups compared with HCs, the DC value in severe CSM group was higher compared with mild-moderate CSM group. (P < 0.05), and the DC values of the right superior temporal gyrus and precuneus showed a decrease after increase. Among them, DC values in the area of precuneus in severe CSM group were significantly lower than those in mild-moderate CSM and HCs. (P < 0.05). The fractional anisotropy (FA) values of the level C2/3 showed a progressive decrease in different clinical stages, that severe CSM group was the lowest, significantly lower than those in mild-moderate CSM and HCs (P < 0.05). There was negative correlation between DC value of left middle temporal gyrus and JOA scores (P < 0.001), and the FA values of dorsal column in the level C2/3 positively correlated with the JOA scores (P < 0.001). CONCLUSION: Structural and functional changes have taken place in the cervical spinal cord and brain of CSM patients. The Brain reorganization plays an important role in maintaining the symptoms and signs of CSM, aberrant DC values in the left middle temporal gyrus may be the possible mechanism of inconsistency between imaging findings and clinical symptoms. Degree centrality is a potentially useful prognostic functional biomarker in cervical spondylotic myelopathy.

Fractional amplitude of low-frequency fluctuation alterations in patients with cervical spondylotic myelopathy: a resting-state fMRI study.

PURPOSE: We sought to use the fractional amplitude of low-frequency fluctuation (fALFF) method to investigate the changes in spontaneous brain activity in CSM patients and their relationships with clinical features. METHODS: We recruited 20 patients with CSM, and 20 healthy controls (HCs) matched for age, sex, and education status. The fALFF method was used to evaluate the altered spontaneous brain activities. The Pearson correlation analysis of fALFF and the clinical features were carried out. RESULTS: Compared with HC, CSM group showed increased fALFF values in the left middle frontal gyrus, inferior parietal lobule, and right angular gyrus. Decreased fALFF values were found in the right lingual gyrus, cuneus (P < 0.05). Pearson correlation analysis shows that the fALFF values of all CSM were positively correlated with JOA score in the right angular gyrus (r = 0.518, P < 0.05). CONCLUSION: CSM patients have abnormal fALFF distribution in multiple brain regions and might be an appealing alternative approach for further exploration of the pathological and neuropsychological states in CSM.

A transition-metal-free azide-alkyne cycloaddition/hydroamination cascade reaction for the construction of triazole-fused piperazin-2-ones.

A time-dependent, divergent synthesis of highly functionalized [1,2,3]triazolo[1,5-a]pyrazin-4(5H)-one (reaction time: 12 h) or 6,7-dihydro-[1,2,3]triazolo[1,5-a]pyrazin-4(5H)-one (reaction time: 2 h) scaffolds via a cascade azide-alkyne cycloaddition/hydroamination protocol is reported. The transformation features good functional group compatibility, broad substrate scope, high atom economy and avoidance of the use of transition-metal catalysts.

An Alkyne-Isocyanide Cycloaddition/Boulton-Katritzky Rearrangement/Ring Expansion Reaction: Access to 9-Deazaguanines.

An alkyne-isocyanide [3 + 2] cycloaddition followed by a Boulton-Katritzky rearrangement and a ring expansion is demonstrated. Different from the typical Boulton-Katritzky rearrangement, which forms five-membered ring products, the rearrangement-ring expansion method provides a mild, efficient, and atom-economical access to fused 9-deazaguanine structures in high yields.

Discovery of 3,5-diaryl-1H-pyrazol-based ureas as potent RET inhibitors.

Rearranged during transfection (RET) is a promising target for antitumor drug development. Multikinase inhibitors (MKI) have been developed for RET-driven cancers but displayed limited efficacy in disease control. Two selective RET inhibitors were approved by FDA in 2020 and proved potent clinical efficacy. However, the discovery of novel RET inhibitors with high target selectivity and improved safety is still highly desirable. Herein, we reported a class of 3,5-diaryl-1H-pyrazol-based ureas as new RET inhibitors. The representative compounds 17a/b displayed high selectivity to other kinases, and potently inhibited isogenic BaF3-CCDC6-RET cells harboring wild-type, or gatekeeper mutation (V804M). They also displayed moderate potency against BaF3-CCDC6-RET-G810C with solvent-front mutation. Compound 17b showed better pharmacokinetics properties and demonstrated promising oral in vivo antitumor efficacy in a BaF3-CCDC6-RET-V804M xenograft model. It may be utilized as a new lead compound for further development.

Hemodialysis catheter-related infection caused by Pannonibacter phragmitetus: a rare case report in China.

Pannonibacter phragmitetus (P. phragmitetus) is rarely related with human disease. We reported a case of catheter-related infection caused by P. phragmitetus in a 68-year-old woman on hemodialysis. The patient developed recurrent fever during hemodialysis and blood cultures were positive for P. phragmitetus. The patient's body temperature returned to normal after intravenous cefoperazone/sulbactam treatment, and the hemodialysis catheter was locked with gentamicin and urokinase. The potential anti-infective treatment against P. phragmitetus was discussed.

Primary renal carcinoid tumors: Three case reports.

RATIONALE: Primary renal carcinoid tumors are very rare and only about 100 cases have been reported in the medical literature. There are even fewer articles on the imaging manifestations of primary renal carcinoid tumors. PATIENT CONCERNS: We present 3 cases of patients with lumbago and hematuria. These were cases of primary renal carcinoid tumors with initial suspicion of suprarenal epithelioma. DIAGNOSES: Renal lesions were detected on abdomen computed tomography (CT) imaging. The 3 cases presented as solid/cystic solid renal mass with uniform or non-uniform density, calcification in the mass, and enhanced heterogeneity. INTERVENTIONS: The laparoscopic partial/radical nephrectomy were performed. OUTCOMES: The postoperative histological diagnosis were primary renal carcinoid tumors. Case 2 been lost to follow-up in 3 patients, and the other 2 patients (Case 1 and 3) are still alive. Case 1 had intrahepatic metastases. LESSONS: Primary renal carcinoid tumors mostly present as solid mass/cystic solid mass with calcification and delayed enhancement of heterogeneity on CT imaging, but the diagnosis depends on pathological diagnosis. Hence, raising awareness of the CT features of the rare tumor in the kidney may broaden the knowledge base of radiologists.

Altered regional homogeneity in delayed encephalopathy after carbon monoxide poisoning: A resting-state fMRI study.

OBJECTIVE: To investigate alternations in spontaneous brain activities reflected by regional homogeneity (ReHo) in patients with delayed encephalopathy after acute carbon monoxide poisoning (DEACMP) using resting-state functional magnetic resonance imaging (rs-fMRI). METHODS: Twenty-one patients with DEACMP and 21 age, sex and education matched healthy controls (HCs) received rs-fMRI scanning and clinical assessment. We used the ReHo method to analyze the interregional synchronized activity of all participants. Two sample t-tests were performed to compare the ReHo maps between the two groups. Pearson correlation analysis was then used to assess the correlations between clinical measures and abnormal ReHo in DEACMP patients. RESULTS: Compared with HCs, DEACMP patients showed significantly decreased ReHo in bilateral cerebellum posterior lobe, pons, bilateral basal ganglia, while increased in the posterior cingulate, calcarine, bilateral occipital lobe(GRF correction, voxel P value <0.001, cluster P value <0.05). Negative correlation was found between Mini-mental State Examination (MMSE) scores and the ReHo values of posterior cingulate gyrus (r = -0.672, p < 0.05) in the DEACMP group, while positively related to the time from CO poisoning to MRI scan (r = 0.428, p < 0.05). CONCLUSION: Patients with DEACMP exhibited altered ReHo in the multiple functional brain regions, which provide evidence for local brain dysfunctions and may help to understand the neuropathologic mechanism for the disease.

Abnormal degree centrality in delayed encephalopathy after carbon monoxide poisoning: a resting-state fMRI study.

PURPOSE: To explore neuropathologic mechanisms in functional brain regions in patients with delayed encephalopathy after carbon monoxide poisoning (DEACMP) from the perspective of the brain network nodes by resting-state functional magnetic resonance imaging (rs-fMRI). METHODS: The fMRI and cognitive assessments were performed in 25 patients with DEACMP and 25 age-, sex- and education-matched healthy controls (HCs). Data analysis was performed via the degree centrality (DC) method. Then, the associations between the cognitive assessments and DC in the identified abnormal brain regions were assessed by using a correlation analysis. RESULTS: Compared with the HCs, the DEACMP patients displayed significantly decreased DC values in the right superior frontal gyrus, right precentral gyrus, right angular gyrus, right marginal gyrus, right hippocampus, and left thalamus but increased DC values in the right inferior frontal gyrus, right cingulate gyrus, left superior temporal gyrus, left medial temporal gyrus, right lingual gyrus, and right posterior cerebellar lobe, pons, and midbrain (GRF correction, voxel P value < 0.001, cluster P value < 0.01). The correlation analysis in the DEACMP group revealed that there was a negative correlation between the DC values in the right hippocampus and MMSE scores, whereas a positive correlation was observed in the right cingulate gyrus. CONCLUSIONS: Patients with DEACMP exhibited abnormal degree centrality in the brain network. This finding may provide a new approach for examining the neuropathologic mechanisms underlying DEACMP.