Objective To compare the epidermal shape built by different passages of keratinocytes and its ability of proliferation and differentiation in three-dimensional conditions.Methods Different passages of keratinocytes were used to construct tissue-engineered skin.The morphology of the tissue-engineered skin was observed with HE and PAS staining,while CK1/CK10,CK5/CK14,Ki67 were detected by immunohistochemical assays.Results All the tissue-engineered skin had a significant dermoepidermal structure.The stratification of 1st and 2nd passage skins were better,and 2nd passage epidermis was thicker than that in other passages (P＜0.05).Dermoepidermal structure in collagen type Ⅳ group binded more tightly,but collagen type Ⅳ had little effect on the thickness of the epidermis (P＞0.05).In collagen type Ⅳ group PAS stain was negative,indicating type Ⅳ collagen was unable to promote the reconstruction of BM in vitro.The Ki-67 proliferation index of the 2nd keratinocyte was similar to the normal skin,the remaining passages keratinocyte proliferation gradually decreased (P＜0.05) ; the 1st and 2nd passage skins expressed CK1/CK10 and CK5/CK14.Conclusions Keratinocytes before the 3rd passage have a better ability in the proliferation and differentiation,and so they are more suitable as seed cells for tissue-engineered skin.

Objective:To compare the effects of intensive and standard blood pressure control on the outcomes of patients with acute ischemic stroke in the anterior circulation who have successfully recanalized after endovascular therapy (EVT).Methods:A multicenter, open-label, blinded-endpoint, randomized controlled design was used. Patients with anterior circulation stroke received EVT and successfully recanalized in Nanjing First Hospital, Nanjing Medical University and several branch hospitals from July 2020 to October 2022 were prospectively included. They were randomly divided into the intensive blood pressure control group (target systolic blood pressure [SBP] 100-120 mmHg) or the standard blood pressure control group (target SBP 121-140 mmHg). The blood pressure of both groups needs to achieve the target within 1 h and maintain for 72 h. The primary outcome endpoint was outcome at 90 d, and the good outcome was defined as a score of 0-2 on the modified Rankin Scale. Secondary outcome endpoints included early neurological improvement, symptomatic intracranial hemorrhage (sICH) within 24 h, and death and serious adverse events within 90 d.Results:A total of 120 patients were included, including 63 in the intensive blood pressure control group and 57 in the standard blood pressure control group. There was no statistically significant difference in baseline characteristics between the two groups. The SBP at 72 h after procedure was 122.7±8.1 mmHg in the intensive blood pressure control group and 130.2±7.4 mmHg in the standard blood pressure control group, respectively. There were no significantly differences in the good outcome rate (54.0% vs. 54.4%; χ2=0.002, P=0.963), the early neurological improvement rate (45.2% vs. 34.5%; χ2=1.367, P=0.242), the incidence of sICH (6.3% vs. 3.5%; P=0.682), mortality (7.9% vs. 14.0%; χ2=1.152, P=0.283) and the incidence of serious adverse events (12.7% vs. 15.8%; χ2=0.235, P=0.628) at 90 d between the intensive blood pressure control group and the standard blood pressure control group. Conclusion:In patients with anterior circulation stroke and successful revascularization of EVT, early intensive blood pressure control don’t improve clinical outcomes and reduce the incidence of sICH.

Letrozole,a third generation non-steroidal aromatase inhibitor,has been approved for the treatment of breast cancer in women.In recent years,it has been used in the field of growth and development in children,such as childhood dwarfism,somatic delayed pubertal growth and precocious puberty,but the long-term effects on liver and kidney function,lipid metabolism,reproductive function and bone metabolism are unclear.Studies have shown that letrozole can cause abnormal testicular morphology,changes in seminiferous tubules and interstitial tissues,reduce bone density,affect the bal-ance of bone metabolism,and cause cognitive impairment and apoptosis of nerve cells.The mecha-nism of reproductive toxicity of letrozole may be related to its influence on the development and matura-tion of testicular cells,the expression of sex hormones and gonadotropins in vivo,and the distribution and expression of estrogen receptors in testicular tissues.The mechanism of bone metabolic toxicity is related to its increase in the proliferation and differentiation of osteoclasts induced by receptor activator of NF-κB ligand,as well as the increase of apoptosis,oxidative stress and NF-κB activity of osteo-blasts.The mechanism of cognitive toxicity is related to its regulation of classical and nonclassical effects of the hippocampus,reduction of glutamate uptake by astrocytes,and reduction of L-type calcium channel blockade of caspase 3 activation.This article is to provide reference for safe and effective use of letrozole in clinical pediatrics.