Prognosis of childhood adrenoleukodystrophy with cognitive disorder after haploidentical allogenic hemato-poietic stem cell transplantation / 中华实用儿科临床杂志

Objective:To investigate the prognosis of childhood adrenoleukodystrophy (ALD) with cognitive disorder after haploidentical allogenic hematopoietic stem cell transplantation (haplo-HSCT), and to identify risk factors affecting the prognosis.Methods:It was a single-center retrospective study involving 31 ALD children receiving haplo-HSCT in Peking University People′s Hospital from January 2014 to October 2022.Survival analysis was performed by Kaplan-Meier method. Cox regression analysis was performed to identify risk factors for the prognosis of childhood ALD following haplo-HSCT. Results:Among the 31 children with ALD, 1 case died of cardiogenic shock during the transplantation, and the remaining had a successful haplo-HSCT.Ten children with ALD had cognitive disorder before haplo-HSCT, including 3 cases with the minimal LOES score ≥10 points and 8 cases with the Neurologic Function Score (NFS)>0 point before haplo-HSCT.Six children had major functional disability (MFD) and 2 cases died due to progression of ALD after haplo-HSCT.Twenty children did not have cognitive disorder before haplo-HSCT, of whom 3 cases had the LOES score≥10 points and 6 cases had NFS>0 before haplo-HSCT.Four children had MFD and 2 cases died due to progression of ALD after haplo-HSCT.For ALD patients without cognitive disorder after haplo-HSCT, the 3-year and 5-year survival rate were 100.0% and 72.9%, respectively, and the 5-year MFD-free survival was 61.6%.For ALD patients with cognitive disorder after haplo-HSCT, the 3-year survival rate was 83.3%.Compared with ALD patients with the LOES score<10 points before haplo-HSCT, those with the LOES score≥10 points had 9.243 times the risk of developing MFD after haplo-HSCT ( P=0.024, 95% CI: 1.332-64.127). Compared with ALD patients without cognitive disorder before haplo-HSCT, ALD patients with cognitive disorder had 9.749 times the risk of developing MFD after haplo-HSCT ( P=0.023, 95% CI: 1.358-66.148). Conclusions:Cognitive disorder and LOES score≥10 points before haplo-HSCT are risk factors for developing MFD in children with ALD following haplo-HSCT.

Effects of minimal persistent inflammation on nasal mucosa of experimental allergic rhinitis in guinea pigs / 中华耳鼻咽喉头颈外科杂志

<p><b>OBJECTIVE</b>To establish an animal model of minimal persistent inflammation (MPI) of allergic rhinitis in guinea pigs and to investigate the changes of nasal mucosa. The expression of transforming growth factor-beta1 (TGF-beta1) and matrix metalloproteinases-9 (MMP-9) were discussed.</p><p><b>METHODS</b>Thirty male Hartley guinea pigs were randomly divided into two groups: MPI model group and control group randomly, with fifteen animals in each group. Guinea pigs from MPI model group were sensitized intraperitoneally by injection of suspension of ovalbumin (OVA) and aluminum hydroxide in 0.9% physiological saline. Then, repeated local booster sensitization with low concentration of OVA suspension into the nasal cavity was performed to establish MPI models. Alcian blue-periodic acid-Schiff (AB-PAS) staining and Masson's trichrome (MT) staining were used to determine the number of goblet cells and collagen deposition within the basement membrane of epithelium. The expression and distribution of TGF-beta1 and MMP-9 in nasal mucosa were estimated by double immunofluorescence under a confocal laser scan microscopy system.</p><p><b>RESULTS</b>Compared with the control group, the increased goblet cells (t = 13.720, P < 0.05) in nasal epithelium together with the increased collagen fibrils (t = 4.542, P <0.05) within the basement membrane of epithelium were observed in the MPI model group. There was nearly no expression of TGF-beta1, in the control group and the expression of MMP-9 was only found in the epithelium cell. In contrast, there was significantly higher expression of TGF-beta1 and MMP-9 (t = 25.218, P <0.05) in nasal mucosa of MPI model group than that in control group. TGF-beta1 mainly expressed in the epithelium cell, the infiltrated inflammatory cell and extracellular matrix, while MMP-9 expressed in the epithelium cell and the infiltrated inflammatory cell.</p><p><b>CONCLUSIONS</b>Long time MPI in allergic rhinitis resulted in some changes of tissue remodeling in nasal mucosa. TGF-beta1 and MMP-9 may play an important role in disease progression.</p>

Establishment and significance of the experimental minimal persistent inflammation models in allergic rhinitis guinea pigs / 中华耳鼻咽喉头颈外科杂志

<p><b>OBJECTIVE</b>To develop an animal model of minimal persistent inflammation (MPI) in allergic rhinitis guinea pigs and to investigate its significance.</p><p><b>METHODS</b>Sixty male Hartley guinea pigs were divided into four groups: group A (positive control group), B (MPI model group), C (negative group) and D (bland group) respectively, with fifteen animals in each group. Guinea pigs from group A, B and C were sensitized intraperitoneally by injection of suspension of ovalbumin (OVA) and aluminum hydroxide in 0.9% physiological saline. Then, repeated local booster sensitization with different concentration of OVA suspension (1% and 0.01%) or physiological saline into the nasal cavity of those guinea pigs were performed. For group D, physiological saline was used only. Symptoms (sneezing) of guinea pigs after antigen challenge were observed and the infiltration of eosinophils (EOS) together with the expression of intercellular adhesion molecule 1 (ICAM-1) in the nasal epithelial cells were also examined.</p><p><b>RESULTS</b>When challenged with 1% OVA, the sneezing number of guinea pigs in group B was increased markedly than that in group D (P < 0.05). However, there was no difference between group B, A and C (P > 0.05). When challenged with 0.01% OVA, the symptom of sneezing almost disappeared in group B just like that in group D and there was no difference between the two groups (P > 0.05). Besides, there was still more EOS infiltrated in the nasal mucosa of guinea pigs in group B than that in group D (P < 0.05). There was no expression of ICAM-1 in nasal epithelium of guinea pigs in group D, nevertheless, ICAM-1 was found mildly expressed in group B.</p><p><b>CONCLUSIONS</b>MPI models have been established successfully through long term challenge with lower density of OVA in the sensitized guinea pigs, which will provide us with a new method for further research in the mechanism and treatment of allergic rhinitis.</p>

Expression of proto-oncogenes c-fos and c-jun in osteoblasts activated by excessive fluoride / 中华预防医学杂志

<p><b>OBJECTIVE</b>To study expression of proto-oncogenes c-fos and its accompanying gene c-jun in osteoblasts activated by action of excessive fluoride in vivo and in vitro.</p><p><b>METHODS</b>Experimental Wistar rats were exposed to sodium fluoride (NaF) added to their drinking water, and NaF was also added in cell culture supernatant for osteoblast-like cells in vitro. Expression of both mRNA and protein of c-fos and c-jun in bone-tissue of rats with chronic fluorosis and cultured osteoblast-like cells were determined by hybridization in situ, Western blot and immunohistochemistry at varied time periods after exposure.</p><p><b>RESULTS</b>Sodium fluoride could stimulate the proliferation of osteoblast in rats with chronic fluorosis and induce expression of both c-fos and c-jun in all envelops of the spine bone, as compared with its control group. Value of optical absorption in mRNA expression of c-fos and c-jun was 139.63 and 126.37, respectively, in rats with NaF plus high-calcium, significantly lower than that in control group with high-calcium only (107.74 and 117.48, respectively) (P < 0.001). Immunohistochemical analysis showed that protein level of c-fos and c-jun was significantly higher in rats with NaF plus high-calcium than that in control rats with high-calcium only, with values of optical absorption of 139.16, 131.15, 149.98 and 149.19 (P < 0.05), respectively, and protein level of c-fos and c-jun was significantly higher in rats with NaF plus low-calcium than that in control rats with low-calcium only, with values of optical absorption of 117.24, 111.46, 132.46 and 129.79 (P < 0.05), respectively. Western blotting showed that level of protein expression of c-fos and c-jun in periosteal osteoblasts was significantly higher in all rat groups with NaF than that in all control groups, with values of optical absorption of 123.32, 116.60, 115.97 and 108.30, respectively. mRNA expression of c-fos and c-jun in osteoblast-like cells treated with NaF for 12 h increased obviously, and remained at high level 48 h after exposure, with values of optical absorption of 114.80, 161.14, 118.20, and 150.41, respectively, as compared with that in control group (P < 0.001 and P < 0.05).</p><p><b>CONCLUSIONS</b>Exposure to excessive fluoride could stimulate activation and proliferation of both osteoblasts in rats and cultured osteoblast-like cells in vitro, and cause enhanced expression of mRNA and protein of both c-fos and c-jun. Over-expression of c-fos could play an important role in development and proliferation of skeletal lesions in rats with chronic fluorosis.</p>