BACKGROUND:Abnormal extracellular matrix accumulation and excessive proliferation of fibroblasts are the main manifestations of pathological scars.Excessive proliferation of fibroblasts leads to the production of large amounts of collagen-based extracellular matrix.Therefore,to investigate the role of fibroblast fibrosis in the formation of pathological scar will provide a new idea for revealing the mechanism of pathological scar and biological therapy. OBJECTIVE:To investigate the effect of RAS-selective lethal small molecule 3(RSL3)on the fibrosis of human pathological scar fibroblasts. METHODS:Then cases of pathological scar tissue and normal skin tissue samples from the same individuals,provided by the Department of Burn Plastic Surgery,General Hospital of Ningxia Medical University,were collected.Fibroblasts of human pathological scar and human normal skin were extracted and used in the following experiments.The general condition of the pathological scar tissue and the normal skin tissue was detected by hematoxylin-eosin staining.The appearance of fibroblasts from pathological scar and normal skin were observed by inverted microscope.The fibroblasts were verified by immunofluorescence assay.The cells were treated with different concentrations of RSL3(1,3,5,7,9,11,13 μmol/L).The inhibitory concentration of RSL3 on fibroblasts was detected by cell counting kit-8.Control group(without treatment)and RSL3 intervention group(treated with 7 μmol/L RSL3 for 24 hours)were set up.The mRNA and protein expressions of glutathione peroxidase 4,type Ⅰ collagen,type Ⅲ collagen and α-smooth muscle actin were detected by Qrt-PCR and western blot,respectively.Level of malondialdehyde in cells was detected.The residual scratch area was measured by cell scratch test after 24 hours to calculate the percentage of residual scratch area. RESULTS AND CONCLUSION:The expression of glutathione peroxidase 4 in the pathological scar group was higher than that in the normal skin group(Mrna:t=3.252,P<0.01;protein:t=5.075,P<0.01).The expression of glutathione peroxidase 4 in the pathological scar fibroblast group was higher than that in the normal skin fibroblast group(Mrna:t=10.32,P<0.01;protein:t=26.22,P<0.01).Compared with the control group,the expression of glutathione peroxidase 4 was decreased(Mrna:t=2.798,P<0.05;protein:t=4.643,P<0.01),the content of malondialdehyde was increased(t=2.917,P<0.05),the expression of type Ⅰ collagen(Mrna:t=15.84,P<0.01;protein:t=4.610,P<0.01),type Ⅲ collagen(Mrna:t=28.86,P<0.01;protein:t=7.713,P<0.01)and α-smooth muscle actin(Mrna:t=2.671,P<0.05;protein:t=7.417,P<0.01)were decreased in the RSL3 intervention group.Compared with the control group,the migration ability was weakened in the RSL3 intervention group(t=14.06,P<0.01).To conclude,RSL3 can inhibit the expression of glutathione peroxidase 4 and then inhibit the ability of fibrosis and migration of pathological scar fibroblasts.

Articular cartilage (AC) injuries often lead to cartilage degeneration and may ultimately result in osteoarthritis (OA) due to the limited self-repair ability. To date, numerous intra-articular delivery systems carrying various therapeutic agents have been developed to improve therapeutic localization and retention, optimize controlled drug release profiles and target different pathological processes. Due to the complex and multifactorial characteristics of cartilage injury pathology and heterogeneity of the cartilage structure deposited within a dense matrix, delivery systems loaded with a single therapeutic agent are hindered from reaching multiple targets in a spatiotemporal matched manner and thus fail to mimic the natural processes of biosynthesis, compromising the goal of full cartilage regeneration. Emerging evidence highlights the importance of sequential delivery strategies targeting multiple pathological processes. In this review, we first summarize the current status and progress achieved in single-drug delivery strategies for the treatment of AC diseases. Subsequently, we focus mainly on advances in multiple drug delivery applications, including sequential release formulations targeting various pathological processes, synergistic targeting of the same pathological process, the spatial distribution in multiple tissues, and heterogeneous regeneration. We hope that this review will inspire the rational design of intra-articular drug delivery systems (DDSs) in the future.

[摘 要] 目的：探讨lncRNA FAM95B1对胶质瘤细胞增殖和迁移能力的影响并探究其相关作用机制。方法： 选取2018年1月至2020年8月于合肥市第三人民医院行手术治疗的38例胶质瘤患者的胶质瘤组织及癌旁组织标本，利用qPCR检测胶质瘤组织与4种细胞系中FAM95B1的表达水平，以表达最低的胶质瘤LN382细胞为研究对象，转染空载质粒（对照组）或pcDNA3.1-FAM95B1质粒（实验组）。MTT法和划痕实验检测FAM95B1对LN382细胞增殖和迁移能力的影响。生物信息学分析技术和双荧光素酶基因报告实验预测并验证FAM95B1与miR-26a-5p及PTEN之间的相互作用机制，应用qPCR和WB法检测FAM95B1对miR-26a-5p和PTEN表达的影响。结果： FAM95B1在胶质瘤组织中的表达明显低于癌旁组织（P<0.01）。FAM95B1在多种胶质瘤细胞系中的表达均明显低于正常脑胶质细胞（均P<0.01）。过表达FAM95B1可以下调LN382细胞的增殖（P<0.05）和迁移能力（P<0.01）。FAM95B1能够靶向结合miR-26a-5p（P<0.01），miR-26a-5p能够靶向结合PTEN mRNA（P<0.01）。过表达FAM95B1可下调LN382细胞中miR-26a-5p的表达（P<0.01），促进PTEN mRNA的表达（P<0.01）。结论：在胶质瘤组织和细胞系中异常低表达的FAM95B1通过发挥竞争性内源RNA的功能抑制miR-26a-5p的表达而增强PTEN蛋白表达，抑制胶质瘤细胞系LN382的增殖和迁移。

Objective The inadvertent lateral ventricle puncture is still a problem in subthalamic nucleus deep brain stimulation (STN-DBS) surgery,to which a solution is found in this study with a better choice of electrode angle in STN-DBS by reconstruction of the lateral ventricle and STN.Methods Forty patients with Parkinson's disease,admitted to our hospital from January 2009 to December 2015,were chosen in our study.According to the MRI data of the patients,the lateral ventricle and STN were reconstructed with mimics software;Evans indexes were measured,and the volume of lateral ventricle was reconstructed.Different lateral ventricle and STN planes were captured by using different Ring angles (50-60°,n=11),and the Slide angles of these planes were measured.The patients were divided into two groups according to their age:Group A (60-79-year-old) and Group B (40-59-year-old);their volume of lateral ventricle was measured and compared between the two groups;the correlation between age and volume of lateral ventricle was analyzed;the difference of electrode angle was compared between the two groups and the right and left side of the same group;according to the Evans indexes,these patients were then divided into three groups,the Slide angle and Ring angles were measured and the different angles between left and right brain and among the Evans groups were analyzed so as to give a recommended angle in the STN-DBS.Results Age was positively related to the volume of lateral ventricle,and left one and right volume of lateral ventricle (Pearson correlation index:0.364,0.384 and 0.362),which had statistical significance (P＜0.05).No significant difference on electrode angle was noted between group A and B of different Ring angles (P＞0.05),while significant difference was noted on right and left electrode angle between the two groups (P＜0.05).Positive correlations were noted between volume of lateral ventricle and both Evans indexes and electrode angle,and difference was noted on electrode angle in different Evans indexes groups (P＜0.05).The recommended angle was listed according to the difference of side and Evans' index.Conclusions Age is positively related to volume of lateral ventricle,however,the correlation between age and angle is not clear.Considering the difference of sides and Evans' index,we make a list of Ring and Slide angles as recommendation for deep brain stimulation.