Objective:To explore the evolution of CT characteristics of the "reversed halo sign" of pulmonary tuberculosis, and to further improve the recognition of its CT signs.Methods:Clinical and CT data of 12 patients with pulmonary tuberculosis who were clinically and pathologically confirmed and accompanied with CT manifestation of "reversed halo sign" in First Affiliated Hospital of Henan University of Science and Technology from August 2013 to April 2020 were analyzed retrospectively. Pathological and imaging contrastl analysis was performed on 1 patient undergoing surgical treatment.Results:Among 12 cases with "reversed halo sign", there were 2 cases with single lesion in unilateral lung, 2 cases with multiple lesions in unilateral lung, and 8 cases with multiple lesions in bilateral lungs. Three cases showed only "reversed halo sign", 9 cases showed both halo-like sign and uniform fireworks sign. "Tree-in-bud "sign was found in all 12 patients in the outer ring of the "reversed halo sign". Eight patients received three or more CT examinations, and six of them showed reduction of density and volume of the "reversed halo sign" after standardized anti-tuberculosis treatment. Under the natural course of the disease in two cases, the overall enlargement of the lesion was observed in 1 case, and the overall density of the lesion was reduced and the outer ring wall of the "reversed halo sign" was thinned in 1 case. The pathology of one case after surgical lobectomy showed granulomatous inflammatory nodules of varying sizes containing Langerhans nodule giant cells in the lung parenchyma. The typical caseous necrotic granulomatous nodules were rare here. The "reversed halo sign" showed dense Langerhans nodules in the outer ring, sparse central areas with fibrous hyperplasia and alveolar wall thickening.Conclusions:The outer ring of "reversed halo sign" of pulmonary tuberculosis shows as "tree-in-bud" sign, and its center shows as the fine reticulation pattern. After effective anti-tuberculosis treatment, both the overall density of "reversed halo sign" and the lesion size reduced. Finally, the lesions mostly present as as fine grid shadows for a long time.

Nowadays potential preclinical drugs for the treatment of nonalcoholic steatohepatitis (NASH) have failed to achieve expected therapeutic efficacy because the pathogenic mechanisms are underestimated. Inactive rhomboid protein 2 (IRHOM2), a promising target for treatment of inflammation-related diseases, contributes to deregulated hepatocyte metabolism-associated nonalcoholic steatohepatitis (NASH) progression. However, the molecular mechanism underlying Irhom2 regulation is still not completely understood. In this work, we identify the ubiquitin-specific protease 13 (USP13) as a critical and novel endogenous blocker of IRHOM2, and we also indicate that USP13 is an IRHOM2-interacting protein that catalyzes deubiquitination of Irhom2 in hepatocytes. Hepatocyte-specific loss of the Usp13 disrupts liver metabolic homeostasis, followed by glycometabolic disorder, lipid deposition, increased inflammation, and markedly promotes NASH development. Conversely, transgenic mice with Usp13 overexpression, lentivirus (LV)- or adeno-associated virus (AAV)-driven Usp13 gene therapeutics mitigates NASH in 3 models of rodent. Mechanistically, in response to metabolic stresses, USP13 directly interacts with IRHOM2 and removes its K63-linked ubiquitination induced by ubiquitin-conjugating enzyme E2N (UBC13), a ubiquitin E2 conjugating enzyme, and thus prevents its activation of downstream cascade pathway. USP13 is a potential treatment target for NASH therapy by targeting the Irhom2 signaling pathway.