ObjectiveTo evaluate the effect of sex on phenotypic stability in mouse models of chemotherapy-induced alopecia (CIA) induced by cyclophosphamide (CYP) or paclitaxel (PTX), and to explore potential mechanisms underlying phenotypic heterogeneity in female mice. MethodsTwenty-eight wild-type specific pathogen-free (SPF) C57BL/6J mice (half male and half female) aged 6-8 weeks were selected for synchronous back hair removal. On the 9th day after hair removal (T0), the mice were randomly divided into a wild-type female CYP group, a wild-type male CYP group, a female negative control group and a male negative control group. Mice in the CYP groups were intraperitoneally injected with a single dose of 120 mg/kg CYP, and mice in the negative control groups were intraperitoneally injected with the same volume of normal saline. Subsequently, the phenotypic changes of the CIA model induced by CYP were continuously observed and photographed. Eleven 6-week-old SPF female C57BL/6J mice underwent bilateral ovariectomy (OVX group). Following successful surgery, these mice and five XY (Sry⁻) mice bred from Four Core Genotypes breeding stock were used to establish the chemotherapy-induced alopecia (CIA) model using the same protocol. Serum was collected from mice in the OVX group, wild-type female CYP group, and wild-type male CYP group on T7 after CYP administration for steroid hormone analysis by mass spectrometry to evaluate the effects of gonadal estrogen and sex chromosome background changes on the stability of the CYP-induced female alopecic phenotype. Finally, twenty SPF C57BL/6J mice aged 6-8 weeks (half male and half female) were randomly divided into a PTX low-dose group and a PTX high-dose group. On the 9th day after simultaneous hair removal, PTX was injected intraperitoneally at a single dose of 80 mg/kg or 120 mg/kg, respectively. Mice from the PTX low-dose group and the PTX high-dose group were continuously observed and photographed to compare the intra-group consistency of the phenotypes of female and male mice. Six SPF C57BL/6J mice (half male and half female) aged 6-8 weeks were used to repeat the construction method of the PTX low-dose group, and the hair follicle histological examination was performed at T0, T4, T7, T14 and T21, respectively, to observe the damage caused by PTX to hair follicle regeneration. ResultsThe phenotypes of CYP-induced male CIA mice are stable and reproducible. There are obvious individual differences in the alopecia phenotype in the CYP-induced female CIA model mice, which may be mainly caused by the differences in the relevant estrogens in the estrous cycle. The difference between OVX+CYP group and XY (Sry⁻) +CYP group disappeared, suggesting that ovarian-derived hormones and XY (Sry⁻) sex chromosome background may be involved in the formation of phenotypic heterogeneity of CYP-induced alopecia in female mice. The mice in the high-dose PTX group and the low-dose PTX group showed a relatively consistent alopecia and regrowth process, and there was no significant sex difference. ConclusionCYP-induced CIA is strongly influenced by sex, and ovariectomy or alteration of the sex chromosome background can improve the consistency of CYP-induced alopecic phenotypes in female mice. PTX-induced CIA shows good phenotypic consistency in both female and male mice, indicating broad applicability across sexes. Taken together, the choice of animal sex in CIA model construction, mechanistic studies, and evaluation of anti-alopecia interventions should take into account the type of chemotherapeutic agent, the study objective, and the required degree of phenotypic stability. Sex should therefore be considered an important variable in model standardization and interpretation of experimental findings.

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.