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Müller细胞生理功能及其在糖尿病视网膜病变中的变化

Müller细胞接触并包裹视网膜神经元细胞体和突触, 对视网膜神经元的功能及代谢起到支持作用; 对维护视网膜细胞外环境的稳定, 如离子、水平衡和血视网膜屏障(BRB)等具有重要调控作用; 可释放神经胶质递质和刺激性神经物质, 通过对神经递质的再吸收循环, 为视网膜神经元提供神经递质前体进而影响神经突触的活性。此外, Müller细胞对病理刺激能够产生反应。该反应一方面具有视网膜神经元保护作用, 如分泌神经营养因子、吸收降解兴奋性毒素、分泌抗氧化剂等, 另一方面也可引起视网膜神经元谷氨酸盐代谢紊乱和离子平衡紊乱, 导致视网膜水肿和神经元变性损伤。Müller细胞对糖尿病视网膜病变(DR)的发生发展具有重要影响。DR可引起Müller细胞增生, 除造成谷氨酸盐代谢紊乱外, 还会引起Müller细胞大量分泌炎症介质和血管内皮生长因子等破坏BRB。深入研究Müller细胞, 对探讨DR的发病及防治具有重要意义。针对Müller细胞靶向转染的腺病毒载体研制成功, 利用两亲肽携带蛋白或抗体直接转染细胞达到抑制DR的效果, 这些方法为早期防治DR提供了新的途径。

视紫红质类及卷曲蛋白受体在糖尿病视网膜病变发生发展中的作用

鸟苷酸结合蛋白偶联受体(GPCRs)是一类膜受体超家族, 被视为最好的药物靶点。在糖尿病视网膜病变(DR)进程中有大量不同亚型GPCRs参与。其中, 视紫红质类和卷曲蛋白(Frizzled)受体广受关注, 研究方向主要为视网膜炎症反应、新生血管生成、神经元和神经胶质细胞损伤等。血管紧张素Ⅱ受体是最为熟知的视紫红质类受体亚家族。应用血管紧张素Ⅱ受体1拮抗剂可显著降低1型糖尿病患者发生DR的可能性, 但无法减缓已并发DR患者的病变进展; 可减缓并发轻中度DR的2型糖尿病患者的病变进展。其他的视紫红质类受体还有趋化因子受体、大麻素相关受体、GPR91、GPR109A、APJ受体等。Frizzled受体是Wnt信号通路重要的膜受体等。在DR动物模型中, 使用Wnt通路阻断剂Dickkopf homolog 1能改善视网膜炎症、血管渗出、新生血管生成等。但Wnt通路参与DR进展的具体机制有待研究。随着对GPCRs与DR关系了解的加深, 未来将有更多以GPCRs为治疗靶点的药物应用于临床, 为DR患者带来福音。

丝裂原活化蛋白激酶信号通路与眼底新生血管性疾病相关性的研究进展

丝裂原活化蛋白激酶（MAPK）信号通路中主要存在3种亚型，分别为细胞外信号调节激酶（ERK）、c-Jun氨基末端激酶（JNK）和p38 MAPK。它们在各亚群内部均存在着类似的、相互独立的三级级联反应，在适当刺激因素下作用于不同的底物可产生不同的细胞生物学效应。眼底新生血管是多种致盲眼病的病理基础，是多种因子相互作用导致促血管生成因子和抗血管生成因子间的平衡失调的结果；而有关多种因子发挥生物效应的MAPK信号通路在眼底新生血管发生发展过程中的作用越来越引起注意。MAPK信号通路在糖尿病视网膜病变、早产儿视网膜病变、老年性黄斑变性、视网膜静脉阻塞等疾病的新生血管形成中发挥重要的调控作用。通过对MAPK信号通路在眼底新生血管作用机制的探索，有助于深入详尽地了解眼部疾病的形成和发展规律，为预防和控制眼底新生血管形成和发展提供新的思路和方案。在未来，针对MAPK信号通路的靶向治疗将成为有效抑制眼底新生血管形成的重要治疗方案之一。

霉菌感染性视神经炎一例

The effects and mechanisms of G protein-coupled receptor 91 on blood-retinal barrier in diabetic rats

ObjectiveTo investigate the effects and mechanisms of G protein-coupled receptor 91 (GPR91) on blood-retinal barrier (BRB) in diabetic rats. MethodsA lentiviral vector of shRNA targeting rat GPR91 and scrambled shRNA were constructed. Healthy male Sprague-Dawley (SD) rats were selected in this study. The 60 rats were randomized into 4 groups and treated as follows:(1) control group (Group A, n=15), the rats received injections of an equal volume of 0.1% citrate buffer; (2) streptozocin (STZ) group (Group B, n=15), the rats received injections of STZ; (3) LV.shScrambled group (Group C, n=15), diabetic rats received an intravitreal injection of 1 μl 1×108 TU/ml scrambled shRNA lentiviral particles at 2 weeks after the induction of diabetes; (4) LV.shGPR91 group (Group D, n=15), diabetic rats received an intravitreal injection of 1 μl 1×108 TU/ml pGCSIL-GFP-shGPR91 lentiviral particles. At 12 weeks after intravitreal injection, immunohistochemistry and Western blot were used to assess the expression of GPR91, p-extracellular signal-regulated kinase(ERK)1/2, t-ERK1/2, p-Jun N-terminal kinase (JNK), t-JNK, p-p38 mitogen-activated protein kinase (MAPK) and t-p38 MAPK. Haematoxylin and eosin (HE) staining and Evans blue dye were used to assess the structure and function of the retinal vessel. Immunohistochemistry enzyme-linked immunosorbent assay (ELISA) was used to test the protein level of VEGF. ResultsImmunohistochemistry staining showed that GPR91 was predominantly localized to the cell bodies of the ganglion cell layer. Western blot showed that GPR91 expression in Group D decreased significantly compared with Group C (F=39.31, P < 0.01). HE staining showed that the retina tissue in Group B and C developed telangiectatic vessels in the inner layer of retina, while the telangiectatic vessels attenuated in Group D. It was also demonstrated in Evans blue dye that the microvascular leakage in Group D decreased by (33.8±4.11)% compared with Group C and there was significant difference (F=30.35, P < 0.05). The results of ELISA showed the VEGF secretion of Group B and C increased compared with Group A and the VEGF expression in Group D was significantly down regulated after silencing GPR91 gene (F=253.15, P < 0.05).The results of Western blot indicated that compared with Group A, the expressions of p-ERK1/2, p-JNK and p-p38 MAPK were significantly upregulated (q=6.38, 2.94, 3.45;P < 0.05). Meanwhile, the activation of ERK1/2 was inhibited by GPR91 shRNA and the difference was statistically significant (F=22.50, P < 0.05). ConclusionsThe intravitreal injection of GPR91 shRNA attenuated the leakage of BRB in diabetic rats. GPR91 regulated the VEGF release and the leakage of BRB possibly through the ERK1/2 signaling pathway.

Investigation on Surgical Treatment of Abdominal Incisional Hernia(Analysis for 78 Cases)

Objective To review the clinical operation methods of abdominal incisional hernia. Methods Classification, operation method and fellow-up of 78 patients with abdominal incisional hernia were retrospectively analyzed. Results The average time of fellow-up was 26 months. Nineteen cases were repaired with simple suture with 3 cases (15.8%) recurrence, 57 cases were repaired with man-made material with 2 case （3.4%） recurrence. Conclusions Individual operation method should be chosen according to body condition, classification of the size of abdominal loss and abdominal hypertension. It is an effective method to repair the hernia of abdominal incision with man-made material.

左心室部分切除减容术治疗终末期扩张型心肌病

Influence of the Wearing Time of Cheneau Scoliosis Brace on Its Clinical Efficacy

目的　探讨比较色努式脊柱侧弯矫形器佩戴时间及功能锻炼对矫正治疗效果的影响。 方法　将2004年7月－20011年7月收治的126例脊柱侧弯患者，按自愿选择分为试验组和对照组，试验组佩戴色努式脊柱侧弯矫形器18～20 h，功能锻炼＞90 min；对照组佩戴侧弯矫形器23 h，功能锻炼30～60 min。对比两组患者治疗前后的Cobb角、顶椎偏离中线距离（AVT）、顶椎旋转度(AVR)、躯干位移（TS）、脊柱柔韧性及肺功能指标的改善。 结果　经X线检查测定，治疗后两组患者的Cobb角、AVT、AVR、TS均低于治疗前（P＜0.01），且试验组明显低于对照组（P＜0.01）。肺功能指标：试验组治疗后肺活量（VC)、第1秒钟用力呼气容积（FEV1）、用力肺活量（FVC）、肺总量（TLC），等均高于治疗前，残气量（RV）低于治疗前（P＜0.01），对照组治疗后VC、FEV1、FVC、TLC均低于治疗前，RV高于治疗前（P＜0.01），且试验组优于对照组（P＜0.01）。功能位Cobb角：两组患者的功能位主弯Cobb角、代偿弯Cobb角均低于治疗前（P＜0.01），且试验组明显低于对照组（P＜0.01）。 结论　色努式脊柱侧弯矫形器每天佩戴18～20 h，并结合适当的体操疗法，呼吸、肌力训练及麦肯基力学疗法，可使肺功能、腰背部肌力、脊柱柔韧性、身体的协调性、以及平衡能力得到改善，从而达到脊柱侧弯治疗的较好效果。

The change of central retinal thickness and subfoveal choroidal thickness in patient with central retinal artery occlusion during short-term treatment

ObjectiveTo observe the center retinal thickness (CRT) and subfoveal choroidal thickness (SFCT) in eyes with central retinal artery occlusion (CRAO) before and after treatment.MethodsA total of 34 patients (34 eyes) diagnosed with CRAO by fundus fluorescence angiography (FFA) were retrospectively analyzed. There were 18 males (18 eyes) and 16 females (16 eyes). The average age was (61.42±14.09) years. The mean onset time was (2.64±3.73) days. The mean hospitalization time was (11.92±4.95) days. The mean axial length (AL) was (23.53±2.04) mm. The best-corrected visual acuity (BCVA), slit-lamp biomicroscopy, indirect ophthalmoscopy, fundus color photography, fundus fluorescein angiography, spectral domain optical coherence tomography (OCT) and AL measurement were performed. BCVA was converted to the logarithm of the minimum angle of resolution (logMAR). According to FFA, visual loss and the results of OCT, patients were divided into 3 groups: incomplete CRAO (15 eyes) , subtotal CRAO (8 eyes), total CRAO (11 eyes). SFCT and CRT in affected and the fellow eye were measured by OCT for enhanced deep imaging. Follow up lasted for 1 month after treatment, with an average follow-up of (34.71±6.82) days. The changes of SFCT, CRT, and BCVA before and after treatment were observed. The correlation between BCVA after treatment and pretreatment CRT was also analyzed.ResultsAfter 1 month of follow-up, the logMAR BCVA in incomplete group, subtotal group and total group were significantly higher than before treatment (t=3.74, 3.61, 3.26; P=0.004, 0.009, 0.017). Before treatment, the average CRT of the contralateral eyes in the total, subtotal and incomplete group were (215.00±19.85), (224.00±22.79), (214.00±8.21) μm, and the mean SFCT were (264.54±121.71), (266.50±58.17), (261.86±90.95) μm. The average CRT of the affected eyes were (353.18±60.26), (280.14±11.08), (266.63±19.65) μm, and the average SFCT were (233.72±111.35), (237.75±53.30), (259.86±98.14) mm. Compared with the fellow eyes, the average CRT in the 3 groups were thickened, and the difference were statistically significant (t=8.274, 3.694, 11.577; P＜0.001, 0.008, ＜0.001); the average SFCT in the total group was decreased, the difference was statistically significant (t=−2.138, P=0.048). The mean CRT among the 3 groups of eyes was statistically significant (F=12.02, P＜0.001). There was no significant difference in the average SFCT (F=0.178, P=0.838). After 1 month follow-up, the mean CRT in the total, subtotal and incomplete group were (231.18±49.28), (219.16±21.34), (217.86±24.98) μm, and the average SFCT were (239.81±109.57), (241.86±42.81), (260.57±91.67) μm. Compared with before treatment, the average CRT in the three groups of eyes were decreased, the difference were statistically significant (t=13.032, 3.711, 4.970; P＜0.001, 0.008, 0.003); the difference in mean SFCT were not statistically significant (t=−0.785, −0.202, −0.078; P=0.466, 0.845, 0.940). Correlation analysis showed that BCVA after treatment was positively correlated with pretreatment CRT (odds ratio=0.578, P=0.002).ConclusionCRAO resulted in CRT in the preliminary stage and became thinner after receiving treatments. There exists a positive correlation between visual outcome and CRT before receiving treatments.

矫形鞋垫对足底筋膜炎患者的近期疗效

目的　研究矫形鞋垫对治疗足底筋膜炎的疗效，并与常规的矫形器干预治疗（夜间背屈固定治疗）和运动疗法（跟腱和足底筋膜牵拉治疗）进行比较探讨其疗效。 方法　将2011年2月－11月收治的足底筋膜炎患者120例按随机数字表法分为矫形鞋垫治疗组（42例）和夜间踝背屈固定治疗组（37例）以及跟腱、足底筋膜牵拉治疗组（41例）。3组患者均于治疗前、治疗2周后和治疗8周后采用视觉模拟评级法以及功能评价评定双足负重时疼痛的强度、患者1周内最长可持续行走时间。 结果　患者治疗2周后及治疗后8周随访发现，3个治疗组的视觉模拟评分和患者最长可持续行走时间较治疗前均有明显提高，组间比较发现，穿戴矫形鞋垫治疗足底筋膜炎疗效优于夜间背屈固定治疗组和跟腱、足底筋膜牵拉治疗组。 结论　穿戴矫形鞋垫治疗足底筋膜炎的近期效果明显，比夜间背屈固定和牵拉跟腱及足底筋膜治疗足底筋膜炎疗效更优。