Developing a mechanically matched decellularized spinal cord scaffold for the in situ matrix-based neural repair of spinal cord injury.

Tissue engineering is a promising strategy to repair spinal cord injury (SCI). However, a bioscaffold with mechanical properties that match those of the pathological spinal cord tissue and a pro-regenerative matrix that allows robust neurogenesis for overcoming post-SCI scar formation has yet to be developed. Here, we report that a mechanically enhanced decellularized spinal cord (DSC) scaffold with a thin poly (lactic-co-glycolic acid) (PLGA) outer shell may fulfill the requirements for effective in situ neuroengineering after SCI. Using chemical extraction and electrospinning methods, we successfully constructed PLGA thin shell-ensheathed DSC scaffolds (PLGA-DSC scaffolds) in a way that removed major inhibitory components while preserving the permissive matrix. The DSCs exhibited good cytocompatibility with neural stem cells (NSCs) and significantly enhanced their differentiation toward neurons in vitro. Due to the mechanical reinforcement, the implanted PLGA-DSC scaffolds showed markedly increased resilience to infiltration by myofibroblasts and the deposition of dense collagen matrix, thereby creating a neurogenic niche favorable for the targeted migration, residence and neuronal differentiation of endogenous NSCs after SCI. Furthermore, PLGA-DSC presented a mild immunogenic property but prominent ability to polarize macrophages from the M1 phenotype to the M2 phenotype, leading to significant tissue regeneration and functional restoration after SCI. Taken together, the results demonstrate that the mechanically matched PLGA-DSC scaffolds show promise for effective tissue repair after SCI.

Serum Biomarkers for Early Diagnosis of Chinese X-CGD Children: Case Reports and a Literature Review.

Since X-linked chronic granulomatosis disease (X-CGD) exhibits no specific clinical symptoms at an early stage, early diagnosis is difficult and depends predominantly on neonatal screening. Therefore, the aim of this study was to explore routine biomarkers for X-CGD in children and provide clues for early diagnosis. The cases of 10 children with X-CGD diagnosed at Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology from 2013 to 2016 and 122 Chinese children with X-CGD reported in the literature were summarized. Serum biomarkers and clinical symptoms at acute infection were organized. A total of 132 children with X-CGD were enrolled in this study. For 55.8% of the patients, the diagnosis was delayed more than one year after the onset of the first symptoms because no typical clinical symptoms manifested. Children with X-CGD at an acute infection stage showed three recurrent signs in terms of serum biomarkers: (1) the total number of white blood cells (especially N%) was increased significantly, accompanied by anemia in some cases; (2) C-reactive protein (CRP) levels were increased significantly; and (3) most of the patients exhibited very high serum IgG levels (>12 g/L). Diagnosis of X-CGD at an early age is difficult because of its nonspecific clinical features. Our study suggested children with X-CGD suffering acute infection show increases in three typical serum biomarkers, which can provide clues for early diagnosis.

Inhibitory Effect of LPS on the Proliferation of Oligodendrocyte Precursor Cells through the Notch Signaling Pathway in Intrauterine Infection-induced Rats.

Periventricular white matter injury (PWMI) is very common in survivors of premature birth, and the final outcomes are a reduction in myelinated neurons leading to white matter hypomyelination. How and (or) why the oligodendrocyte lineage develops abnormally and myelination is reduced is a hot topic in the field. This study focuses on the effect of intrauterine inflammation on the proliferation of oligodendrocyte lineage cells and the underlying mechanisms. Lipopolysaccharide (LPS) (300 µg/kg) was intraperitoneally injected into pregnant Sprague-Dawley rats at embryonic days 19 and 20 to establish a rat model of intrauterine infection-induced white matter injury. Corpus callosum tissues were collected at postnatal day 14 (P14) to quantify the number of oligodendrocytes, the number and proliferation of oligodendrocyte precursor cells (OPCs), and the expression of myelin proteins (MBP and PLP). Furthermore, the expression of Wnt and Notch signaling-related proteins was analyzed. The results showed that the number of oligodendrocytes in the corpus callosum tissues of LPS-treated rats was reduced, and the expression levels of myelinating proteins were down-regulated. Further analysis showed that the Notch signaling pathway was down-regulated in the LPStreated group. These results indicate that intrauterine LPS may inhibit the proliferation of OPCs by down-regulating the Notch rather than the Wnt signaling pathway, leading to hypomyelination of white matter.

GnRH agonist treatment for idiopathic central precocious puberty can improve final adult height in Chinese girls.

OBJECT: To study the outcomes of GnRHa on final adult height in Chinese idiopathic central precocious puberty (ICPP) girls and the involved factor(s) that can predict height gain. METHODS: We conducted a retrospective analysis on 10 years of data obtained from three clinical hospitals from January 2005 to March 2015, and 101 girls with ICPP, who received GnRHa therapy for more than six months and already reached their adult height were enrolled. RESULTS: Height, bone age, midparent height, HtSDS, sexual development, therapy duration and predicted adult height(PAH)at start and end of GnRHa, and the final adult height(FAH) were recorded and calculated. Their PAH significantly increased at end of GnRHa (158.4±6.00cm), compared to that at the start of GnRHa(153.1±5.37cm) (P<0.001), and their final adult height(157.0±4.82) significantly increased compared to PAH at start of GnRHa(P<0.001). There was no difference between PAH at end of GnRHa and FAH(P>0.05). After GnRHa therapy, most of the ICPP girls reached their midparent height compared to that at start of GnRHa(P<0.01). FAH was positively correlated with Ht at start, and end of GnRHa, PAH at start and end of GnRHa, and also with midparent height (R2 =0.59, 0.74, 0.68, 0.73 and 0.80, P<0.001). While FAH was not correlated with the duration of treatment and BA at start of GnRHa(R2 = 0.15and 0.1, P>0.05). The percentage of adult short stature decreased and those reached midparent height significantly increased after GnRHa therapy, compared to that at start of GnRHa(60.6% vs.30.4% and 67.85% vs. 94.64%, respectively, P<0.05). CONCLUSIONS: GnRHa therapy to ICPP girls can effectively achieve the final adult height. After GnRHa therapy, most of these patients reached their midparent height, while few of these patients had an adult short stature.