Mechanical properties and immunotherapeutic effects of dissolving microneedles with different drug loadings based on hyaluronic acid

Abstract Improving vaccine immunity and reducing antigen usage are major challenges in the clinical application of vaccines. Microneedles have been proven to be painless, minimally invasive, highly efficient, and have good patient compliance. Compared with traditional transdermal drug delivery, it can effectively deliver a large-molecular-weight drug into the skin, resulting in a corresponding immune response. However, few studies have examined the relationship between microneedle loading dose and immune effects. In this study, the hyaluronic acid (HA) conical and pyramidal dissolving microneedles were prepared by the two-step vacuum drying method, respectively. The model drug ovalbumin (OVA) was added to HA to prepare dissolving microneedles with different loading amounts. The mass ratios of HA to OVA were 5:1, 5:3, and 5:5. The mechanical properties of the dissolving microneedles were characterized using nanoindentation and in vitro puncture studies. The immune effects of the matrix and drug content were studied in Sprague-Dawley (SD) rats. Finally, the diffusion behavior of OVA and the binding mode of HA and OVA in the microneedles were simulated using Materials Studio and Autodocking software. The experimental results showed that the conical microneedles exhibited better mechanical properties. When the mass ratio of HA to OVA was 5:3, the immune effect can be improved by 37.01% compared to subcutaneous injection, and achieved a better immune effect with relatively fewer drugs. This conclusion is consistent with molecular simulations. This study provides theoretical and experimental support for the drug loading and efficacy of microneedles with different drug loadings

Unilateral versus bilateral antegrade selective cerebral perfusion technique in aortic surgery: A systematic review and meta-analysis / 中国胸心血管外科临床杂志

@#Objective    To investigate the clinical efficacy of unilateral antegrade selective cerebral perfusion (UASCP) compared to bilateral antegrade selective cerebral perfusion (BASCP) in aortic surgery. Methods    PubMed, EBSCO, Web of Science, Cochrane Library, CBM, CNKI, Wanfang Database were searched from establishment of each database to January 2019 to identify clinical studies on prognosis of UASCP versus BASCP in aortic surgery patients. The quality of randomized controlled trials was assessed by Cochrane risk assessement tool. The quality of non-randomized controlled trials was assessed by the Newcastle-Ottawa Scale ( NOS). Meta-analyses were presented in terms of odds ratio (OR) with 95% confidence interval (CI) by using RevMan 5.3 software. Results    Sixteen eligible studies including 3 randomized controlled trials, 2 propensity matching score studies, and 11 retrospective case control studies including 4 490 patients were identified. The 3 randomized controlled trials were with high bias risk. The NOS score of the other 13 studies was more than 6 stars. Pooled analysis showed no significant difference between the UASCP and BASCP groups in terms of permanent neurological dysfunction (PND) (OR=0.93, 95%CI 0.74 to 1.18, P=0.57), temporary neurological dysfunction (TND) (OR=1.26, 95%CI 0.94 to 1.69, P=0.12), acute kidney injury rate (OR=1.11, 95%CI 0.79 to 1.55, P=0.55), 30-day mortality (OR=0.94, 95%CI 0.67 to 1.32, P=0.72), length of ICU stay (OR=–0.64, 95%CI –1.66 to 0.37, P=0.22) and hospital stay (OR=–0.35, 95%CI –2.38 to 1.68, P=0.74). Conclusion    This meta-analysis shows that UASCP and BASCP administration do not result in different mortality and neurologic morbidity rates. However, more studies with good methodologic quality and large sample are still needed to make further assessment.

Effect of curcumin on angiogenesis of rats with DEN-induced hepatocellular carcinoma under hypoxia / 中国肿瘤生物治疗杂志

@#[Abstract] Objective: To investigate the effect of curcumin on angiogenesis in rats with DEN (diethylnitrosamine)-induced HCC (hepatocellular carcinoma) under hypoxia. Methods: Rat HCC was induced by DEN, and its hepatic hypoxia model was established by ligating hepatic artery. The rats with established HCC model were randomly divided into four groups according to digital table method: lipiodol embolization group (group A), lipiodol combined with curcumin embolization group (group B), lipiodol combined with peripheral liver capsule group (group C), lipiodol combined with curcumin and peripheral liver capsule group (group D), with 10 rats in each group. VEGF expression in HCC cells and tissues, microvessel density (MVD), and median survival time (MST) of rats in each group were compared. Results: VEGF protein expression and microvessel density in group B, D were significantly lower than those in A group ( P <0.01), while those in C group had no significant difference compared with group A ( P >0.05). MST in group B, C and D was significantly longer than that in group A ( P <0.05), and the MST in group D was higher than that in group B and C ( P <0.05). Conclusion: Curcumin can inhibit tumor angiogenesis and decrease VEGF expression and MVD in HCC rats under hypoxia, thus further prolong the survival time of the rats.

Effect of dexmedetomidine on prognosis of patients after cardiac surgery with cardiopulmonary bypass: A systematic review and meta-analysis / 中国胸心血管外科临床杂志

@#Objective     To evaluate the clinical efficacy of dexmedetomidine in perioperative management of on-pump cardiac surgery. Methods     Randomized controlled trials (RCTs) were identified through a systematic literature search of PubMed, EBSCO, Web of Science, Cochrane Library, CBM, CNKI, Wanfang Database (up to December 2016). RevMan 5.3 software was used for meta-analysis. Results     Sixteen studies with 1 432 patients were included. Dexmedetomidine significantly decreased the risk of postoperative delirium (RR=0.28, 95% CI 0.18 to 0.44, P<0.000 01) and postoperative atrial fibrillation (RR=0.65, 95% CI 0.44 to 0.98, P=0.04) compared with the controls. The duration of intubation (RR=–1.96, 95% CI –2.07 to –1.86, P<0.000 01), length of ICU stay (RR=–0.49, 95% CI –0.74, –0.24, P=0.000 1) and hospital stay (RR=–1.24, 95% CI –2.26 to –0.22, P=0.02) in the dexmedetomidine group were significantly shorter than those of the control group. In addition, dexmedetomidine was shown to improve the score of the the Montreal Cognitive Assessment (RR=0.88, 95% CI 0.42 to 1.35, P=0.000 2) compared to the control group. Conclusion     Dexmedetomidine can reduce the complications after cardiac surgery, which is safe and effective. However, more studies with good methodologic quality and large samples are still needed to make further assessment.