Objective To investigate the effect of Yes-associated protein(YAP)on intervertebral disc nucleus pulposus cells and its possible mechanism.Methods The relatively normal and degenerative intervertebral disc tissues of patients who underwent lumbar surgery in our hospital from March 2021 to July 2022 were harvested,and then the expression of YAP in the tissues were detected by immunohistochemistry assay and Western blotting.Human primary nucleus pulposus cells were isolated and primarily cultured,and treated with IL-1β to induce degeneration.Then the cells was divided into control group,IL-1β group,IL-1β+LV-YAP group,IL-1β+YAP-siRNA group,and IL-1β+LV-YAP+3-MA group.Western blot analysis was used to detect the expression of the proteins related to extracellular matrix catabolism and autophagy in each group.Finally,a rat model of disc degeneration was established,and the expression of YAP and LC3 and disc degeneration were observed with MRI,Alcian blue staining and immunohistochemistry.Results The expression level of YAP was significantly lower in the degraded disc tissues than the relatively normal disc tissues(P＜0.05).The IL-1β+LV-YAP group had significantly increased protein levels of Collagen Ⅱ,Aggrecan,and LC3-11(P＜0.05),and decreased levels of MMP-3 and MMP-13(P＜0.05)when compared with the cells after IL-1β treatment,whereas the IL-1β+YAP-siRNA group showed the exact opposite effects.What's more,pretreatment with autophagy inhibitor 3-MA resulted in decreased number of GFP-LC3 positive particles and protein levels of Collagen Ⅱ,Aggrecan and LC3-Ⅱ(P＜0.05),and increased protein expression of MMP-3 and MMP-13(P＜0.05)in comparison with the conditions in the IL-1β+LV-YAP group.Furthermore,YAP overexpression promoted LC3 expression and inhibited disc degeneration in rat model of disc degeneration.Conclusion YAP overexpression can inhibit extracellular matrix degradation by promoting autophagy in human nucleus pulposus cells and thus delaying disc degeneration.

Tumor immunotherapy occupies a pivotal position in the field of hematological malignancies.Chimeric antigen receptor(CAR)T-cell therapy has established a new therapeutic pattern for hematological immunotherapy and achieved satisfactory clinical results in the treatment of B-lineage hematological malignancies.However,CAR T-cell therapy has some limitations in the treatment of T-cell acute lymphoblastic leukemia because of the presence of CAR T-cell fratricide,tumor cell contamination,T-cell aplasia,and other clinically relevant problems.Therefore,the current major challenge is overcoming the existing bottlenecks to optimize CAR-T therapy and improve its efficacy against T-ALL while improving the prognosis of patients.

Objective: To learn the mutation types and hearing screening results in local newborns of Zhoushan,in order to provide evidence for prevention and early detection of deafness. Methods: The newborns in Zhoushan Maternal and Child Health Hospital from August 2015 to May 2018 were recruited and detected by matrix-assisted laser desorption ionization time of flight mass spectrometry（MALDI-TOF-MS）for twenty-two mutation sites of GJB2,SLC26A,GJB3 and 12SrRNA genes. The results of genotyping and hearing screening were analyzed and the hearing condition of abnormal newborns was followed up. Results: Among 4 029 newborns,180（4.47%）newborns were identified to carry mutations,including 94 males（4.66%）and 86 females （4.28%）. There was no statistically significant difference in the rate of carrying mutations between male and female infants （P>0.05）. Totally 135 （3.35%）newborns failed in primary hearing screening,13（9.63%）of whom carried the deafness genes;3 894（96.65%）newborns passed,167（4.29%）of whom carried the deafness gene. There was statistically significant difference in the the rate of carrying mutations between newborns who passed and failed in primary hearing screening （P<0.05）. Eleven newborns were diagnosed with hearing loss,with a rate of 2.73‰. Among 180 mutations identified,there were 91 GJB2 mutations（2.26%）,57 SLC26A4 mutations（1.41%）,14 GJB3 mutations （0.35%）,15 mtDNA 12SrRNA mutations （0.37%）and 3 with mutations of two genes （0.07%）. Sixteen mutation sites （184 cases）were found,and the detection rate was 4.57%. Conclusion The rate of carrying deafness genes in Zhoushan newborns was 4.47%. The deafness genes found were mainly GJB2 and SLC26A4,the carrying rate of mtDNA 12SrRNA gene mutation was also high.