A flexible split prime editor using truncated reverse transcriptase improves dual-AAV delivery in mouse liver

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Correlation study of increase of pharyngeal airway space after mandibular advancement,taking natural head position into consideration

The increase in the pharyngeal airway space after mandibular advancement has not been well explained, and in this study we aimed to show whether there is a correlation in the increase of pharyngeal airway space as a consequence of the mandibular advancement or of the relative change between the mandibular position and the natural head position (NHP). Fifteen patients who had bilateral sagittal split osteotomy for mandibular advancement with or without genioplasty were studied retrospectively. The primary variables of mandibular position, NHP, and pharyngeal airway space were measured in three dimensions using preoperative and postoperative cone-beam computed tomographic datasets and were compared using the paired t test. The secondary variable of pharyngeal airway space was defined as the square root of the mean cross-sectional area (CSA^1/2) of the pharyngeal airway space. Pearson’s correlation coefficient was used to find out whether there was a correlation between the change in CSA^1/2 and the change in mandibular position, or the relative change between the mandibular position and the NHP. Volumes and minimal cross-sectional areas were increased in the pharyngeal airway space, and lengths of airways decreased. Correlation existed only between the increase in CSA^1/2 and the relative change between the mandibular position and NHP. The increase in pharyngeal airway space after mandibular advancement correlated with the relative changes between the mandibular position and the NHP.     

Notch1 contributes to TNF-α-induced proliferation and migration of airway smooth muscle cells through regulation of the Hes1/PTEN axis

Notch1 has been implicated in asthma pathogenesis. However, the function of Notch1 in regulating airway smooth muscle (ASM) cell proliferation and migration during airway remodeling of asthma remains unknown. Using an in vitro model induced by tumor necrosis factor (TNF)-α, we reported in this study that Notch1 participated in TNF-α-induced proliferation and migration of ASM cells. Our results demonstrated that Notch1 expression was significantly upregulated in ASM cells exposed to TNF-α. Notch1 inhibition significantly repressed TNF-α-induced ASM cell proliferation and migration, while Notch1 overexpression promoted the opposite effect. Moreover, Notch1 inhibition downregulated the expression of Notch-1 intracellular domain (NICD) and Hes1, while upregulated PTEN expression in TNF-α-exposed cells. Notably, Hes1 overexpression partially reversed the Notch1-inhibition-mediated inhibitory effect on TNF-α-induced ASM cell proliferation and migration. In addition, the promoting effect of Notch1 inhibition on PTEN expression was markedly abrogated by Hes1 overexpression. Overall, these findings demonstrated that Notch1 inhibition repressed TNF-α-induced ASM cell proliferation and migration by modulating the Hes1/PTEN signaling axis, a finding that highlights the involvement of Notch1/Hes1/PTEN in regulating airway remodeling of asthma.     

Split liver transplantation is utilized infrequently and concentrated at few transplant centers in the United States

Split liver transplantation (SLT) is 1 strategy for maximizing the number of deceased donor liver transplants. Recent reports suggest that utilization of SLT in the United States remains low. We examined deceased donor offers that were ultimately split between 2010 and 2014. SLTs were categorized as “primary” and “secondary” transplants. We analyzed allocation patterns and used logistic regression to evaluate factors associated with secondary split discard. Four hundred eighteen livers were split: 54% from adult, 46% from pediatric donors. Of the 227 adult donor livers split, 61% met United Network for Organ Sharing “optimal” split criteria. A total of 770 recipients (418 primary and 352 secondary) were transplanted, indicating 16% discard. Ninety‐two percent of the 418 primary recipients were children, and 47% were accepted on the first offer. Eighty‐seven percent of the 352 secondary recipients were adults, and 7% were accepted on the first offer. Of the 352 pairs, 99% were transplanted in the same region, 36% at the same center. In logistic regression, shorter donor height was associated with secondary discard (odds ratio 0.97 per cm, 95% CI 0.94‐1.00, P = .02). SLT volume by center was not predictive of secondary discard. Current policy proposals that incentivize SLT in the United States could increase the number of transplants to children and adults.     

Do positional changes of the inferior alveolar canal after sagittal split mandibular osteotomy affect neurosensory recovery?

The purpose of this study was to assess the pre- and postoperative position and dimensions of the inferior alveolar canal (IAC) following sagittal split osteotomy (SSO) and identify any association with postoperative neurosensory deficit (NSD) at 1 year. This retrospective cohort study enrolled consecutive patients who had SSO performed to correct skeletal malocclusion. The pre- and postoperative cone beam computed tomography data were superimposed to visualize differences in IAC position and dimensions. Subjective and objective neurosensory tests were used to determine NSD in the inferior alveolar nerve distribution. A total of 20 subjects were included. The preoperative distance from the lateral cortex of the IAC to the inner aspect of the lateral cortex of the mandible was significantly greater in sides with NSD when compared to sides without NSD (P = 0.01). A significantly greater reduction in the postoperative distance measurement was seen in sides with NSD when compared to sides without NSD (P = 0.01). The magnitude of mandibular movement was significantly increased in sides with NSD (P = 0.02). The preoperative location of the IAC, as well as certain changes in the mediolateral and vertical positions as a result of SSO, are risk factors for postoperative NSD.     

银屑病患者皮损间充质干细胞的培养鉴定及其表达HES1和CXCL6的研究

【摘要】 目的 培养鉴定银屑病患者皮损处真皮间充质干细胞（DMSC），并研究DMSC的发状分裂相关增强子1（HES1）和趋化因子配体6（CXCL6）表达情况。方法 分离培养15例银屑病患者皮损及18例正常人皮肤的DMSC，利用流式细胞仪进行表型鉴定，实时荧光定量聚合酶链反应（RT-PCR）及免疫印迹（Western blot）检测HES1和CXCL6的mRNA及蛋白表达水平，两组间比较采用t检验。结果 银屑病组DMSC形态与正常对照组无差异，但HES1 和CXCL6基因的mRNA水平分别是对照组的3.56和3.44倍，且差异有统计学意义（P < 0.05）。在蛋白水平，银屑病组DMSC中HES1和CXCL6的表达明显高于对照组（P < 0.05）。结论 银屑病患者皮肤DMSC HES1及CXCL6表达升高可能参与银屑病的发病。     

Patterns of lingual split and lateral bone cut end and their associations with neurosensory disturbance after bilateral sagittal split osteotomy

The purpose of this study was to characterize the patterns of lingual split and lateral bone cut end (LBCE) after bilateral sagittal split osteotomy (BSSO) in patients and identify their associations with postoperative neurosensory disturbance. This retrospective cohort study recruited 273 patients with skeletal malocclusion who received BSSO. The postoperative cone beam computed tomography data were reconstructed to three-dimensionally view the patterns of lingual split and LBCE. Associations between lingual split and LBCE and their effects on neurosensory disturbance in the lower lip and chin were determined. Six types of lingual split and three types of LBCE were defined based on three-dimensional images. Type I lingual split as a vertical fracture line to the inferior mandibular border was the most common (40.29%). Inferior LBCE was the most prevalent, followed by lingual and buccal types. Significant associations among lingual split, LBCE and skeletal deformities were found (P < 0.05). However, patterns of lingual split and LBCE were not associated with the incidence of neurosensory disturbance. Patterns of lingual split after BSSO significantly associated with types of LBCE and dentomaxillofacial deformities, but not with postoperative neurosensory disturbance.     

Split AAV-Mediated Gene Therapy Restores Ureagenesis in a Murine Model of Carbamoyl Phosphate Synthetase 1 Deficiency

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