Rong Lin

In this study, we prepared gelatin-coated mesoporous hollow silica nanospheres (GSN) as a drug carrier to improve the water solubility and regulate the release rate of glimepiride (GLM). GLM was loaded into GSN by an absorption method, and drug-loaded samples (GLM-GSN) were characterized by differential scanning calorimeter (DSC) and X-ray diffraction (XRD). Cellular uptake and in vivo intestinal uptake experiments were performed in rats. In addition, the studies of in-vitro drug dissolution, pharmacokinetics, and pharmacodynamic experiments also were performed. GLM-GSN showed excellent drug loading (39.7% ± 0.7%) and sustained GLM release. The state of GLM in GSN was amorphous according to DSC and XRD results. Cellular uptake and in vivo intestinal uptake experiments indicated that GSN could be effectively absorbed, and an MTT experiment demonstrated that GSN had good biocompatibility. Furthermore, the GLM-GSN had a higher bioavailability in pharmacokinetics experiments and a prominent hypoglycemic effect on type-2 diabetes model rats in pharmacodynamic experiments. This study clearly shows that GSN is a promising platform for delivering GLM for the treatment of type-2 diabetes.

Lycium barbarum polysaccharide (LBP) is an alkaloid extracted from lycium barbarum. LBP is the active component of lycium barbarum used to treat hypertension, atherosclerosis and other cardiovascular diseases in Chinese traditional medicine. However, the underlying cellular and molecular mechanisms of LBP- mediated activity in vascular disease remain poorly understood. In the present study, we showed the protective effect of LBP in vascular smooth muscle cells. Our results indicate that LBP significantly reduces the proliferation of VSMCs caused by Homocysteine (Hcy) and inhibits the phenotypic transformation of VSMCs caused by Hcy, from contractile to synthetic. LBP inhibited the protein expression of PI3K and Akt caused by Hcy, and increased the expression of miR-145. The results indicate that LBP exhibits substantial therapeutic potential for the treatment of Hcy-induced VSMCs proliferation and phenotypic transformation through inhibition of PI3K/Akt signaling pathway.

The proliferation, migration, and cellular morphology of vascular smooth muscle cells (VSMCs) play important roles in the pathogenesis of atherosclerosis (AS). Homocysteine (Hcy) is a sulfur-containing amino acid, which is an intermediate product of methionine metabolism. Hcy can induce proliferation, migration, and phenotypic switch of VSMCs, but details of these mechanisms are still unclear. The phosphatidylinositol 3-kinase (PI3K/Akt/mTOR) signaling pathway is involved in a host of cellular functions. In this study, we sought to determine if this multifunctional pathway played a role in Hcy-induced proliferation, migration, and phenotypic transformation of VSMCs, which has not been previously reported. miR-145 has been previously reported to suppress the effects of Hcy in VSMCs. In our study, using qRT-PCR, we found that Hcy itself reduced the expression of miR-145 in VSMCs, while overexpression of miR-145 reduced the proliferation, migration, and phenotypic transformation of VSMCs caused by Hcy. Using Western blot analysis, we found that VSMCs exposed to Hcy exhibited significant increases in the levels of PI3K, Akt, and mTOR proteins. Additionally, overexpression of miR-145 dramatically decreased PI3K, Akt, and mTOR expression. Using qRT-PCR we found that miR-145 expression increased after blocking PI3K using an inhibitor. Inhibition of the PI3K signaling pathway also prevented Hcy-induced VSMC proliferation, migration, and phenotypic switch. Taken together, our results suggest that miR-145 could inhibit VSMC proliferation, migration, and phenotype switching by preventing activation of the PI3K/Akt/mTOR signaling pathway.

Different polymorphic forms can affect the performance of the drug product. In addition, isomorphic crystals show different chemical and physical properties due to the changes in the crystal habit. However, it is unclear whether the crystal habit results in different pharmacological activity. The aim of this study was to investigate whether the pharmacological effect of ibuprofen could be affected due to the variety of the crystal habit. Solvent change technique and conventional fusion method were carried out to modify the characteristics of ibuprofen. The physicochemical properties of each were investigated using powder X-ray diffraction (PXRD), Fourier transform infrared (FT-IR) spectroscopy and differential scanning calorimetry (DSC) techniques. Results of scanning electron microscopy (SEM) analysis revealed differences in the surface characteristics of the crystals obtained. Further study revealed that the samples crystallized exhibited the remarkable variation on the dissolution profiles in different dissolution medium. Moreover, in vivo antinociceptive and anti-inflammatory findings demonstrated that the crystal habit modifications resulted in the different therapeutic efficacy. Taken together, these results indicate that the modification of the crystal habit had a great influence on the in vivo pharmacological activity of ibuprofen crystals.

三维（3D）打印作为一种新兴的快速成型技术，已广泛应用于生物医学领域。3D 打印最初在医学中主要用于可视化模型、模具的构建，但随着生物医学领域 3D 打印技术的发展，该技术逐渐应用在复杂组织再生和器官重构等方面，通过生物 3D 打印获得的人工组织和器官，有望用于器官移植以及进行新药研发和药物毒性评价等医药学相关的研究。本文重点阐述了 3D 打印技术在肝脏外科中的个体化应用，并重点介绍了生物 3D 打印技术在肝移植、药物肝脏代谢和肝毒性评价中的研究进展，并进一步对其未来发展趋势进行了展望。

AIM: To clarify this controversy and to provide evidence for application of lipid lowering agents in treatment of diabetic retinopathy (DR). METHODS: We searched the databases of PubMed, Embase and Cochrane Library Central Register of Controlled Trials (CENTRAL) and abstracts from main annual meetings up to January 1, 2017. Google scholar and ClinicalTrials. gov were also searched for unpublished relevant studies. We included randomized controlled trials (RCTs) that studied lipid-lowering agents in type 1 or type 2 diabetes in this Meta-analysis. The primary endpoint was the progression of DR, and the secondary endpoints included vision loss, development of diabetic macular edema (DME) and aggravation of hard exudates. The pooled odds ratios (OR) with corresponding 95% confidence intervals (95% CIs) were calculated. RESULTS: After systemic and manual literature search by two independent investigators, we included 8 RCTs from 7 published articles with 13 454 participants in this Meta-analysis. The results revealed that lipid-lowering drugs were associated with reduced risk in DR progression [OR= 0.77 (95% CI: 0.62, 0.96), P=0.02]. Lipid-lowering agents might have protective effect on DME compared to placebo, although the difference was not statistically significant [OR= 0.60 (95% CI: 0.34, 1.08), P=0.09]. However, no significant differences in the worsening of vision acuity [OR= 0.96 (95% CI: 0.81,1.14), P=0.64] and hard exudates [OR= 0.50 (95% CI: 0.15, 1.74), P=0.28] were found between the lipidlowering drugs and the placebo groups. CONCLUSION: In DR patients, lipid-lowering agents show a protective effect on DR progression and might be associated with reduced risk in the development of DME. However, lipid-lowering agents have no effects on vision loss and hard exudates aggravation. Further clinical trials in larger scale are required to confirm the conclusion of this study and thus justify the use of intensive control lipids with anti-lipid agents at the early stages of DR.

Aims: To investigate the loss of retinal nerve fiber layer (RNFL) in type-2 diabetic patients with early-stage diabetic retinopathy (DR) and to identify potential risk factors accounting for these alterations. Methods: In this cross-sectional study, 158 type-2 diabetic patients were divided into three groups based on their DR status. RNFL thickness and other optic disc parameters were obtained by optical coherence tomography (OCT) and then compared among different groups. We investigated the potential association between RNFL loss and systemic risk factors for DR, including diabetes duration, body mass index (BMI), serum lipids, hemoglobin A1c (HbA1c) and albumin-creatinine ratio (ACR). One-way ANOVA was carried out to compare RNFL thickness among different groups, Pearson correlation and multivariate linear regression analysis were performed to determine potential risk factors related to RNFL thickness in these patients. Results: There were significant differences in the average (F = 8.872, P = 0.003), superior (F = 8.769, P = 0.004), and inferior (F = 8.857, P = 0.003) RNFL thickness of both eyes among the groups, but no obvious difference in optic disc parameters was found. Diabetic duration, BMI, TG, High density lipoprotein cholesterol (HDL), HbA1c, and ACR were found negatively related to the RNFL thickness in both or single eye according to Pearson correlation analysis. After controlling for age, gender, and axis length (AL) in multivariate linear regression analysis, the diabetic duration was associated significantly with RNFL thickness of superior in both eye (right eye: p = 0.016, left eye: p = 0.024), BMI was related to the nasal quadrant of the right eye (p = 0.034), and TG was related to the inferior of the right eye (p = 0.037), HbA1c (p = 0.026) was associated significantly with the average RNFL thickness of the right eye. In addition, ACR was found negatively related to average (p = 0.042) and inferior quadrant (p = 0.014) of the left eye, respectively. Conclusions: RNFL loss might be the earliest structural change of retina in diabetic patients, and associated with diabetic duration, BMI, TG, HbA1c, and ACR. The conclusions of this study need to be proved by other well-matched and large-scale prospective clinical trials in the future, because the correlations discovered in our study were weak.

Oral candidiasis or thrush is a fungal infection due to Candida albicans, causing discomfort in areas inside mouth or tongue. The clinical application of antifungal reagent amphotericin B (AMB), which is believed to offer a better treatment for oral candidiasis, is greatly compromised by its toxicities (mainly nephrotoxicity) and poor solubility. In order to overcome these issues, we characterized AMB-loaded MPEG-PCL micelles in vitro and in vivo. In addition, the antifungal activities of AMB/MPEG-PCL micelles-loaded buccal tablet were also evaluated in vitro. We found that micelles system could significantly improve the solubility of AMB yet reduce the overall toxicity, while the buccal tablet system is capable to suppress C. albicans biofilm formation. Furthermore, the toxicity of the buccal tablet system is also reduced compared with other standard preparations. Therefore, the prepared tablet with AMB-loaded MPEG-PCL micelles as oral topical preparations has the potential to improve current treatment of superficial oral C. albicans infections.