Proteomics approach on microcystin binding proteins in mouse liver for investigation of microcystin toxicity.

Microcystins (MC) produced by freshwater cyanobacteria are potent hepatotoxins. MC inhibit protein phosphatases (PP) 1 and 2A. MC and okadaic acid (OA), which is a similar PP inhibitor whereas it has a less affinity to PP1 than PP2A, behave similarly to primary culture hepatocytes, with inducements of phosphorylations of cytoskeleton, morphological changes and apoptosis. Although the distribution of OA in mouse liver was observed immunohistochemically, no OA injury was found. The purpose of this study was therefore to determine why only MC has specific toxicities on the liver. A systematic process of MC affinity chromatography and proteomics, using two-dimensional gel electrophoresis and MALDI-TOFMS, indicated the existence of some MC-binding proteins including the complexes of PP1, PP2A, and PP4 with their own regulatory subunits in mouse liver extracts. The competitive inhibition experiments using affinity chromatography with OA showed that two of the three protein complexes strongly interacted with OA, whereas only the complex of PP1 with the inhibitory subunit NIPP1 did not strongly interacted with OA. These results suggest that the PP1 complex is not related to the common behavior of MC and OA of primary culture hepatocytes, and is related to the specific hepatotoxicities of MC.     

Glutathione depletion is a major determinant of inhaled naphthalene respiratory toxicity and naphthalene metabolism in mice.

Naphthalene (NA) is metabolized to highly reactive intermediates that are primarily detoxified by conjugation to glutathione (GSH). Intraperitoneal administration of naphthalene causes substantial loss of both hepatic and respiratory GSH, yet only respiratory tissues are injured in mice. The liver supplies GSH to other organs via the circulation, making it unclear whether respiratory GSH losses reflect in situ respiratory depletion or decreased hepatic supply. To address this concern, mice were exposed to naphthalene by inhalation (1.5-15 ppm; 2-4 h), thereby bypassing first-pass hepatic involvement. GSH levels and histopathology were monitored during the first 24 h after exposure. Half of the mice were given the GSH depletor diethylmaleate (DEM) 1 hour before naphthalene exposure. Lung and nasal GSH levels rapidly decreased (50-90%) in mice exposed to 15 ppm naphthalene, with cell necrosis throughout the respiratory tract becoming evident several hours later. Conversely, 1.5 ppm naphthalene caused moderate GSH loss and only injured the nasal olfactory epithelium. Neither naphthalene concentration depleted hepatic GSH. Animals pretreated with DEM showed significant GSH loss and injury in nasal and intrapulmonary airway epithelium at both naphthalene concentrations. DEM treatment, perhaps by causing significant GSH loss, decreased water-soluble naphthalene metabolite formation by 48% yet increased NA-protein adducts 193%. We conclude that (1) GSH depletion occurs in airways independent of hepatic function; (2) sufficient GSH is not supplied by the liver to maintain respiratory GSH pools, or to prevent injury from inhaled naphthalene; and (3) GSH loss precedes injury and increases protein adduct formation.     

Purines Change at Acupoints along the Pericardium Meridian in Healthy and Myocardial Ischemic Rats

Objective: To quantify the purine concentrations of the acupoints along the pericardium and nonpericardium meridians under healthy and myocardial ischemia conditions to investigate the relationship between acupoint purine change and body functional status in rats. Methods: A total of 70 rats underwent an operation for myocardial ischemia, while 40 of them survived. They were randomly assigned to the following 5 subgroups: Neiguan (PC 6), Quze (PC 3), Tianquan (PC 2), Quchi (LI 11), and Jianyu (LI 15). Simultaneously, another 40 healthy rats were also randomized into the same 5 subgroups as the control group. The tissue fluids at the acupoints were collected by microdialysis for 30 min. Subsequently, the concentration of adenosine triphosphate (ATP), adenosine diphosphate (ADP), adenosine monophosphate (AMP), and adenosine (ADO) were quantified using the high-performance liquid chromatography method. Results: Compared with the healthy group, the ADO at PC 6 (P=0.012), PC 3 (P=0.038), PC 2 (P=0.024), and LI 15 (P=0.042) obviously increased in the model group, while no significant difference was observed at LI 11 (P=0.201). However, ATP, ADP, and AMP manifested no significant changes in these areas, except for ATP at LI 15 (P=0.036). Conclusions: Myocardial ischemia could induce an increase in ADO at acupoints of the upper arm and shoulder area, suggesting that the body functional status could affect the responsiveness of acupoints. The status of these acupoints could be pathogenically activated by disease, and distribution following some specific courses.     

孔源性视网膜脱离并发脉络膜脱离患者的角膜内皮形态学参数

目的：探讨孔源性视网膜脱离并发脉络膜脱离(RRD-CHD)患者的角膜内皮细胞形态学参数变化。

方法：连续收集RRD-CHD患者70例70眼,分为无高度近视组(A组)38眼38眼、高度近视组(B组)32例32眼,另收集正常组(C组)36例36眼。使用角膜内皮镜检测各组角膜内皮细胞最小面积(S_min)、最大面积(S_max)、平均面积、平均密度(CD)、细胞面积标准差(SD)、变异系数(CV)及六角形细胞比例(HG)。

结果：RRD-CHD患者和正常组的角膜内皮细胞CD、HG均有差异(P<0.001)。A组的CD与B组、C组均有差异(P<0.05),B组与C组有差异(P<0.001)。在A组中,SD、CV与眼轴(r_s=-0.426、0.494, 均P<0.01),CD与眼压、眼轴(r_s=-0.025、0.368, 均P<0.05),HG与病程(r_s=0.552, P<0.05)均相关。在RRD-CHD患者中,SD、CV与眼轴(r_s=0.236、0.159, 均P<0.05),HG与病程(r_s=0.142, P<0.05),S_max与眼压(r_s=-0.314, P<0.01)均相关。

结论：RRD-CHD患者持续低眼压状态下角膜内皮细胞的HG和CD均明显降低,眼轴、病程和眼压可影响角膜内皮的形态学参数。     

高度近视患者白内障术后视力与椭圆体带完整性的相关性

目的：分析高度近视白内障患者超声乳化联合IOL植入术后视力预后的影响因素,初步探讨椭圆体带完整性与术后视力的相关性。

方法：回顾性病例研究。将临床确诊为高度近视合并白内障患者96例106眼纳入研究。术前检查后所有患者均行白内障超声乳化联合IOL植入术,对比分析术前及术后1wk,1、3、6mo患眼BCVA变化,比较不同BCVA分段手术前后患眼椭圆体带的完整性,同时分析影响患者术后视力的相关影响因素。

结果：术前和术后1wk,1、3、6mo患眼BCVA分别为0.80(0.50, 1.70)、0.51(0.28, 1.30)、0.50(0.09, 0.60)、0.30(0.22, 0.90)、0.30(0.22, 0.70),有差异(P<0.001); 术前和术后6mo不同BCVA分段患眼椭圆体带完整性,均有差异(P<0.001)。多元逐步回归分析显示,术后6mo时BCVA与术前BCVA和椭圆体带完整性具有相关性(P<0.05); 和性别、年龄、术前平均角膜曲率、眼轴无相关性(P>0.05)。

结论：高度近视白内障患者经超声乳化吸除联合IOL植入术后视力改善,术后视力与椭圆体带完整性和术前视力具有相关性。     

有晶状体眼后房型人工晶状体植入与FS-LASIK术后视觉质量分析

目的：比较有晶状体眼后房型人工晶状体(ICL)植入与FS-LASIK术治疗中高度近视术后的视觉质量。

方法：前瞻性研究。选取2018-06/12分别行ICL植入术和FS-LASIK术的近视患者58例116眼(ICL组)和48例96眼(FS-LASIK组)。分析比较两组患者手术前后屈光度、视力和视觉质量情况。

结果：术后3mo,ICL组患者球镜度数高于FS-LASIK组(0.19±0.22D vs 0.09±0.29D,P<0.05),但两组患者视力、柱镜度数和等效球镜度数无差异(均P>0.05); ICL组患者调制传递函数截止频率(MTF cut off)、客观散射指数(OSI)和OV9%均明显优于FS-LASIK组,而SR较FS-LASIK组降低,且与术前相比,ICL组患者MTF cut off明显增高,SR、OSI值降低,FS-LASIK组患者SR值降低(均P<0.05)。

结论：ICL植入和FS-LASIK术均可有效改善患者视力和屈光度,对于中高度近视患者ICL植入术可提供相对较好的视觉质量。     

有晶状体眼后房型人工晶状体植入术对高度近视的疗效

目的：通过双通道客观视觉质量分析系统Ⅱ(OQAS Ⅱ)评价有晶状体眼后房型人工晶状体(ICL)植入术对高度近视的临床疗效。

方法：选取2017-12/2018-12安徽医科大学第一附属医院收治的高度近视患者26例52眼,所有患者均行ICL植入术。随访获取所有患者术前BCVA以及术前和术后1wk,1、3mo的UCVA、客观散射指数(OSI)、调制传递函数(MTF)、斯特列尔比(SR)和100%、20%及9%的模拟对比度视力(Predicted VA)等一系列参数。

结果：与术前BCVA相比,术后1wk,1、3mo UCVA情况均优于术前且日渐改善(P<0.01)。与术前OSI、MTF、SR和Predicted VA 100%、20%及9%相比,术后1wk,1、3mo情况均好转(P<0.01)。

结论：ICL植入术能够有效地矫正高度近视,提高裸眼视力。通过OQAS Ⅱ分析,ICL植入术后OSI比术前减小,术后的MTF、SR和Predicted VA 100%、20%及9%比术前均有提高,高度近视患者视觉质量得到良好的改善。     

Evaluation of spectral domain optical coherence tomography parameters in discriminating preperimetric glaucoma from high myopia

AIM: To evaluate the diagnostic ability of macular ganglion cell-inner plexiform layer (GCIPL) thickness obtained by spectral-domain optical coherence tomography (SD-OCT) in discriminating non-highly myopic eyes with preperimetric glaucoma (PPG) from highly myopic healthy eyes. METHODS: A total of 254 eyes, including 76 normal controls (NC), 116 eyes with high myopia (HM) and 62 non-highly myopic eyes with PPG were enrolled. The diagnostic ability of OCT parameters was accessed by the areas under the receiver operating characteristic (AUROC) curve in two distinguishing groups: PPG eyes with non-glaucomatous eyes including NC and HM (Group 1), and PPG eyes with HM eyes (Group 2). Differences in diagnostic performance between GCIPL and RNFL parameters were evaluated. RESULTS: The minimum (AUROC curve of 0.782), inferotemporal (0.758) and inferior (0.705) GCIPL thickness were the top three GCIPL parameters in discriminating PPG from non-glaucomatous eyes, all of which had statistically significant lower diagnostic ability than average RNFL thickness (0.847). In discriminating PPG from HM, the best GCIPL parameter was minimum (0.689), statistically significant lower in diagnostic ability than average RNFL thickness (0.789) and three other RNFL thickness parameters of temporal and inferotemporal clock-hour sectors. CONCLUSION: The minimum GCIPL thickness is the best GCIPL parameter to detect non-highly myopic PPG from highly myopic eyes, whose diagnostic ability is inferior to that of average RNFL thickness and RNFL thickness of several temporal and inferotemporal clock-hour sectors. The average RNFL thickness is recommended for discriminating PPG from highly myopic healthy eyes in current clinical practice in a Chinese population.     

高胰岛素血症伴高氨血症综合征1例报告并文献复习

目的探讨GLUD1基因变异所致高胰岛素血症伴高氨血症综合征临床表现和致病基因特点。方法回顾分析1例高胰岛素血症伴高氨血症综合征患儿的临床资料,并复习相关文献。结果女性患儿,1岁9个月起病,反复出现血糖偏低2年余,并惊厥发作3次,给予升血糖、止惊对症处理后可缓解;伴血胰岛素、血氨水平升高,诊断为高胰岛素血症伴高氨血症综合征。高通量测序发现患儿GLUD1基因存在错义变异c.965GA,p.Arg322His(杂合),其父母该位点均为正常基因型,为新生突变。结论基因检测有助于明确高胰岛素血症伴高氨血症综合征诊断。