Siqing Huang

3D-engineering of Cellularized Conduits for Peripheral Nerve Regeneration.

Tissue engineered conduits have great promise for bridging peripheral nerve defects by providing physical guiding and biological cues. A flexible method for integrating support cells into a conduit with desired architectures is wanted. Here, a 3D-printing technology is adopted to prepare a bio-conduit with designer structures for peripheral nerve regeneration. This bio-conduit is consisted of a cryopolymerized gelatin methacryloyl (cryoGelMA) gel cellularized with adipose-derived stem cells (ASCs). By modeling using 3D-printed “lock and key” moulds, the cryoGelMA gel is structured into conduits with different geometries, such as the designed multichannel or bifurcating and the personalized structures. The cryoGelMA conduit is degradable and could be completely degraded in 2-4 months in vivo. The cryoGelMA scaffold supports the attachment, proliferation and survival of the seeded ASCs, and up-regulates the expression of their neurotrophic factors mRNA in vitro. After implanted in a rat model, the bio-conduit is capable of supporting the re-innervation across a 10 mm sciatic nerve gap, with results close to that of the autografts in terms of functional and histological assessments. The study describes an indirect 3D-printing technology for fabricating cellularized designer conduits for peripheral nerve regeneration, and could lead to the development of future nerve bio-conduits for clinical use.

Adjunctive brivaracetam for patients with refractory partial seizures: A meta-analysis of randomized placebo-controlled trials

OBJECTIVE To evaluate the clinical efficacy and safety of the newer antiepileptic drug (AED), brivaracetam (BRV), as adjunctive therapy for adults with refractory partial seizures. METHODS Randomized-controlled trials (RCTs) of BRV in the treatment of refractory partial seizure were systematically reviewed and quantified using fixed- or random-effects meta-analysis. 50% responder rate, seizure free rate and adverse events in the treatment period were analyzed as outcomes for measuring efficacy and safety. Pooled effects of risk ratio (RR) and 95% confidence interval (CI) were derived from meta-analysis implemented in RevMan 5.2. RESULTS Five RCTs were identified for inclusion, and included a total of 1639 patients. The pooled RR of BRV vs. placebo as adjunctive therapy for adults with refractory partial seizure was 1.80 (95% CI 1.43-2.26, P < 0.00001) for 50% responder rates, 4.11 (95% CI 1.39-12.21, P = 0.01) for seizure free rates, 1.08 (95% CI 0.73-1.59; P = 0.70) for withdrawal rates. There was no evidence of a statistically significant association between the use of BRV and most adverse events, except somnolence (RR 1.63, 95% CI 1.08-2.45, P = 0.02) and fatigue (RR 2.05, 95% CI 1.19-3.53, P = 0.009). CONCLUSION This study confirmed significant effects of BRV as adjunctive treatment of refractory partial seizures. This study also demonstrated the good tolerability profile of adjunctive BRV for patients with epilepsy. Further large clinical and pharmacovigilance studies are needed to investigate the long-term efficacy and safety of BRV and, furthermore, to suggest an optimal BRV dosage for clinical use.

RNF213 polymorphism and Moyamoya disease: A systematic review and meta-analysis

BACKGROUND Recent genome-wide and locus-specific association studies identified RNF213 as an important Moyamoya disease (MMD) susceptibility gene. But the results of these studies are limited by the few subjects, different methodologies and ethnicities. AIMS To investigate the association between p.R4810K (rs 112735431, ss179362673; G > A) and p.R4859K (c.14576 G > A) polymorphisms of the RNF213 gene and MMD susceptibility. SETTINGS AND DESIGN We conducted a meta-analysis to evaluate the association. MATERIALS AND METHODS Two investigators independently searched the PubMed, Medline, and Embase databases for studies published before October 2012. For included studies, we performed meta-analyses using Cochrane RevMan software. STATISTICAL ANALYSIS Summary odds ratios (ORs) and 95% confidence intervals (CIs) for RNF213 p.R4810K and p.R4859K polymorphisms; MMD were calculated in a fixed-effects model and a random effects model whenever appropriate. RESULTS Five eligible studies were reviewed and analyzed, which included two studies for p.R4810K polymorphisms (421 cases and 1214 controls) and three studies for p.R4859K polymorphisms (398 cases and 765 controls). Overall, the pooled results indicated that both p.R4810K polymorphisms and p.R4859K polymorphisms were associated with MMD risk (OR 92.03, 95% CI 54.06-156.65, P < 0.00001 and OR 157.53, 95% CI 85.37-290.7, P < 0.00001, respectively). Stratified analyses by ethnicity revealed the population attributable risks in the Japanese and Korean populations were larger than that in the Chinese population (P =0.0006). CONCLUSIONS This meta-analysis demonstrated that there are strong associations between p.R4859K and p.R4810K polymorphisms of the RNF213 gene and MMD. The discoveries of its association with MMD may help in early diagnosis and prevention of this disease. Further study is still necessary to clarify the biochemical function and pathological role of RNF213 in MMD.

Symptomatic Rathke cleft cyst

Rathke cleft cysts (RCC) are uncommon intrasellar lesions. Although their clinical manifestations, radiological features and treatment are frequently reported, controversy remains as a result of their rarity. We reviewed the preoperative clinical manifestations, neurological examination findings, visual acuity and fields, endocrinological function, radiographic study findings, surgical and pathological records, and prognosis of 45 patients with RCC (21 males, 24 females, average age: 47 years) admitted to our department between January 2002 and January 2011. The most common clinical manifestations included headaches, and visual and hormonal disturbances. Most RCC were intrasellar with a suprasellar extension. The most common MRI patterns were hypointense on T1-weighted and hyperintense on T2-weighted images, isointense on T1-weighted and hyperintense on T2-weighted images, and hyperintense on T1-weighted and hyperintense on T2-weighted images. Aspiration and biopsy of the cyst wall were performed in most patients. Most patients experienced improved headaches and visual disturbance, but the hormonal disturbance rarely returned to normal, especially in those patients with a serious preoperative hormonal disturbance. The recurrence rate was 14%, which was associated with the extent of cyst removal, inflammation and rim enhancement, as well as the surgical approach. Aspiration and biopsy of the cyst wall still seems to be an effective treatment for most RCC for its low morbidity and good prognosis. Conservative treatment and close follow-up may be suitable for small cysts with subtle clinical manifestations.

Aberrant membranous expression of β-catenin predicts poor prognosis in patients with craniopharyngioma ☆

The objective of this study is to investigate β-catenin expression in craniopharyngioma patients and determine its significance in predicting the prognosis of this disease. Fifty craniopharyngioma patients were enrolled in this study. Expression of β-catenin in tumor specimens collected from these patients was examined through immunostaining. In addition, mutation of exon 3 in the β-catenin gene, CTNNB1, was analyzed using polymerase chain reaction, denaturing high-pressure liquid chromatography, and DNA sequencing. Based on these results, we explored the association between membranous β-catenin expression, clinical and pathologic characteristics, and prognoses in these patients. Of all craniopharyngioma specimens, 31 (62.0%) had preserved membranous β-catenin expression, whereas the remaining 19 specimens (38.0%) displayed aberrant expression. Statistical analysis showed a significant correlation between aberrant membranous β-catenin expression and CTNNB1 exon 3 mutation, as well as between aberrant membranous β-catenin expression and the histopathologic type of craniopharyngioma and type of resection in our patient population. Furthermore, aberrant membranous β-catenin expression was found to be associated with poor patient survival. Results of Kaplan-Meier survival analysis and Cox regression analysis further confirmed this finding. In conclusion, our study demonstrated that aberrant membranous β-catenin expression was significantly correlated with poor survival in patients with craniopharyngioma. This raises the possibility for use of aberrant membranous β-catenin expression as an independent risk factor in predicting the prognosis of this disease.

Intradiploic hemangioma with repeated hemorrhage in a child with hemophilia

Intraosseous hemangioma is an uncommon benign vascular tumor, which is most frequently found in middle-aged female patients. The clinical course is usually insidious and the outcome excellent after total resection. The authors report a case of a calvarial hemangioma in a child with hemophilia who experienced a catastrophic postoperative hematoma and discuss the mechanism, clinical features, and treatment of this condition.

A minimally invasive technique for decompression of Chiari malformation type I (DECMI study): study protocol for a randomised controlled trial

Introduction Chiari malformation type I (CM-I) is a congenital hindbrain anomaly that requires surgical decompression in symptomatic patients. Posterior fossa decompression with duraplasty (PFDD) has been widely practiced in Chiari decompression, but dural opening carries a high risk of surgical complications. A minimally invasive technique, dural splitting decompression (DSD), preserves the inner layer of the dura without dural opening and duraplasty, potentially reducing surgical complications, length of operative time and hospital stay, and cost. If DSD is non-inferior to PFDD in terms of clinical improvement, DSD could be an alternative treatment modality for CM-I. So far, no randomised study of surgical treatment of CM-I has been reported. This study aims to evaluate if DSD is an effective, safe and cost-saving treatment modality for adult CM-I patients, and may provide evidence for using the minimally invasive procedure extensively. Methods and analysis DECMI is a randomised controlled, single-masked, non-inferiority, single centre clinical trial. Participants meeting the criteria will be randomised to the DSD group and the PFDD group in a 1:1 ratio. The primary outcome is the rate of clinical improvement, which is defined as the complete resolution or partial improvement of the presenting symptoms/signs. The secondary outcomes consist of the incidence of syrinx reduction, postoperative morbidity rates, reoperation rate, quality of life (QoL) and healthcare resource utilisation. A total of 160 patients will be included and followed up at 3 and 12 months postoperatively. Ethics and dissemination The study protocol was approved by the Biological and Medical Ethics Committee of West China Hospital. The findings of this trial will be published in a peer-reviewed scientific journal and presented at scientific conferences. Trial registration number ChiCTR-TRC-14004099.

Blood coagulation factor XIII-A subunit Val34Leu polymorphisms and intracerebral hemorrhage risk: A meta-analysis of case-control studies

Background. Previous studies investigating the association between factor XIII-A subunit (FXIII-A) Val34Leu polymorphisms and intracerebral hemorrhage (ICH) had provided inconsistent results and no large systematic review or meta-analysis had been conducted regarding this issue. Methods. We conducted a meta-analysis to confirm whether the FXIII-A Val34Leu polymorphisms increased the risk of ICH. Relevant studies were identified from the Pubmed, Medline, Embase, China National Knowledge Infrastructure, and Chinese Biomedicine Databases published up to September 2013. Summary odds ratios (ORs) and 95% confidence intervals (CIs) for FXIII-A Val34Leu polymorphisms and ICH were calculated in a fixed-effects model or a random-effects model when appropriate. We also carried out the stratified analyses and sensitivity analyses by region, source of control group, and sample size. Results. Eight eligible studies were reviewed. As FXIII Val34Leu was absent or had a very low prevalence among East Asians, only six studies in Caucasians were analyzed, involving 564 cases and 1276 controls. Overall, the Leu allele of FXIII gene had a trend to slightly increased odds of having ICH, but there is no statistic significance (OR1.23, 95% CI 0.94–1.61, P = 0.13). The OR of genotypes Leu+(Leu/Leu or Leu/Val) for the risk of ICH was 1.21, 95% CI 0.98–1.50, P = 0.08. And the OR of recessive model genotypes was 1.53, 95% CI 0.81–2.88, P = 0.19. There was no difference of the association between the Leu allele of FXIII gene and risk of ICH in stratified analysis. Conclusions. Our meta-analysis suggests that there is no evidence for strong association between FXIII Val34Leu polymorphisms and ICH, but Leu allele of FXIII gene might slightly increase the risk of ICH in Caucasians. Since limited studies and subjects were included, larger scale association studies exploring the gene–gene interactions and gene–environment interactions are necessary to further validate the association.