Adaptation of prelimbic cortex mediated by IL-6/STAT3/Acp5 pathway contributes to the comorbidity of neuropathic pain and depression in rats.

BACKGROUND: The adaption of brain region is fundamental to the development and maintenance of nervous system disorders. The prelimbic cortex (PrL) participates in the affective components of the pain sensation. However, whether and how the adaptation of PrL contributes to the comorbidity of neuropathic pain and depression are unknown. METHODS: Using resting-state functional magnetic resonance imaging (rs-fMRI), genetic knockdown or overexpression, we systematically investigated the activity of PrL region in the pathogenesis of neuropathic pain/depression comorbid using the combined approaches of immunohistochemistry, electrophysiology, and behavior. RESULTS: The activity of PrL and the excitability of pyramidal neurons were decreased, and the osteoclastic tartrate-resistant acid phosphatase 5 (Acp5) expression in PrL neurons was upregulated following the acquisition of spared nerve injury (SNI)-induced comorbidity. Genetic knockdown of Acp5 in pyramidal neurons, but not parvalbumin (PV) neurons or somatostatin (SST) neurons, attenuated the decrease of spike number, depression-like behavior and mechanical allodynia in comorbidity rats. Overexpression of Acp5 in PrL pyramidal neurons decreased the spike number and induced the comorbid-like behavior in naïve rats. Moreover, the expression of interleukin-6 (IL-6), phosphorylated STAT3 (p-STAT3) and acetylated histone H3 (Ac-H3) were significantly increased following the acquisition of comorbidity in rats. Increased binding of STAT3 to the Acp5 gene promoter and the interaction between STAT3 and p300 enhanced acetylation of histone H3 and facilitated the transcription of Acp5 in PrL in the modeled rodents. Inhibition of IL-6/STAT3 pathway prevented the Acp5 upregulation and attenuated the comorbid-like behaviors in rats. CONCLUSIONS: These data suggest that the adaptation of PrL mediated by IL-6/STAT3/Acp5 pathway contributed to the comorbidity of neuropathic pain/depression induced by SNI.

Cardiac T1 and T2 Mapping Showed Myocardial Involvement in Recovered COVID-19 Patients Initially Considered Devoid of Cardiac Damage.

BACKGROUND: Myocardial injury has been found using magnetic resonance imaging in recovered coronavirus disease 2019 (COVID-19) patients unselected or with ongoing cardiac symptoms. PURPOSE: To evaluate for the presence of myocardial involvement in recovered COVID-19 patients without cardiovascular symptoms and abnormal serologic markers during hospitalization. STUDY TYPE: Prospective. POPULATION: Twenty-one recovered COVID-19 patients and 20 healthy controls (HC). FIELD STRENGTH/SEQUENCE: 3.0 T, cine, T2-weighted imaging, T1 mapping, and T2 mapping. ASSESSMENT: Cardiac ventricular function includes end-diastolic volume, end-systolic volume, stroke volume, cardiac output, left ventricle (LV) mass, and ejection fraction (EF) of LV and right ventricle (RV), and segmental myocardial T1 and T2 values were measured. STATISTICAL TESTS: Student's t-test, univariate general linear model test, and chi-square test were used for analyses between two groups. Ordinary one-way analyses of variance or Kruskal-Wallis H test were used for analyses between three groups, followed by post-hoc analyses. RESULTS: Fifteen (71.43%) COVID-19 patients had abnormal magnetic resonance findings, including raised myocardial native T1 (5, 23.81%) and T2 values (10, 47.62%), decreased LVEF (1, 4.76%), and RVEF (2, 9.52%). The segmental myocardial T2 value of COVID-19 patients (49.20 [46.1, 54.6] msec) was significantly higher than HC (48.3 [45.2, 51.7] msec) (P < 0.001), while the myocardial native T1 value showed no significant difference between COVID-19 patients and HC. The myocardial T2 value of serious COVID-19 patients (52.5 [48.1, 57.1] msec) was significantly higher than unserious COVID-19 patients (48.8 [45.9, 53.8] msec) and HC (48.3 [45.2, 51.7]) (P < 0.001). COVID-19 patients with abnormally elevated D-dimer, C-reactive protein, or lymphopenia showed higher myocardial T2 values than without (all P < 0.05). DATA CONCLUSION: Cardiac involvement was observed in recovered COVID-19 patients with no preexisting cardiovascular disease, no cardiovascular symptoms, and elevated serologic markers of myocardial injury during the whole course of COVID-19. LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY: Stage 5.

Precise localization of microvascular invasion in hepatocellular carcinoma based on three-dimensional histology-MR image fusion: an ex vivo experimental study.

Background: Microvascular invasion (MVI) is an independent risk factor for postoperative recurrence of hepatocellular carcinoma (HCC). However, MVI cannot be detected by conventional imaging. To localize MVI precisely on magnetic resonance (MR) images, we evaluated the feasibility and accuracy of 3-dimensional (3D) histology-MR image fusion of the liver. Methods: Animal models of VX2 liver tumors were established in 10 New Zealand white rabbits under ultrasonographic guidance. The whole liver lobe containing the VX2 tumor was extracted and divided into 4 specimens, for a total of 40 specimens. MR images were obtained with a T2-weighted sequence for each specimen, and then histological images were obtained by intermittent, serial pathological sections. 3D histology-MR image fusion was performed via landmark registration in 3D Slicer software. We calculated the success rate and registration errors of image fusion, and then we located the MVI on MR images. Regarding influencing factors, we evaluated the uniformity of tissue thickness after sampling and the uniformity of tissue shrinkage after dehydration. Results: The VX2 liver tumor model was successfully established in the 10 rabbits. The incidence of MVI was 80% (8/10). 3D histology-MR image fusion was successfully performed in the 39 specimens, and the success rate was 97.5% (39/40). The average registration error was 0.44±0.15 mm. MVI was detected in 20 of the 39 successfully registered specimens, resulting in a total of 166 MVI lesions. The specific location of all MVI lesions was accurately identified on MR images using 3D histology-MR image fusion. All MVI lesions showed as slightly hyperintense on the high-resolution MR T2-weighted images. The results of the influencing factor assessment showed that the tissue thickness was uniform after sampling (P=0.38), but the rates of the tissue shrinkage was inconsistent after dehydration (P<0.001). Conclusions: 3D histology-MR image fusion of the isolated liver tumor model is feasible and accurate and allows for the successful identification of the specific location of MVI on MR images.