γ-Aminobutyric Acid Regulates Both the Survival and Replication of Human β-Cells

γ-Aminobutyric acid (GABA) has been shown to inhibit apoptosis of rodent β-cells in vitro. In this study, we show that activation of GABA_A receptors (GABA_A-Rs) or GABA_B-Rs significantly inhibits oxidative stress–related β-cell apoptosis and preserves pancreatic β-cells in streptozotocin-rendered hyperglycemic mice. Moreover, treatment with GABA, or a GABA_A-R– or GABA_B-R–specific agonist, inhibited human β-cell apoptosis following islet transplantation into NOD/scid mice. Accordingly, activation of GABA_A-Rs and/or GABA_B-Rs may be a useful adjunct therapy for human islet transplantation. GABA-R agonists also promoted β-cell replication in hyperglycemic mice. While a number of agents can promote rodent β-cell replication, most fail to provide similar activities with human β-cells. In this study, we show that GABA administration promotes β-cell replication and functional recovery in human islets following implantation into NOD/scid mice. Human β-cell replication was induced by both GABA_A-R and GABA_B-R activation. Hence, GABA regulates both the survival and replication of human β-cells. These actions, together with the anti-inflammatory properties of GABA, suggest that modulation of peripheral GABA-Rs may represent a promising new therapeutic strategy for improving β-cell survival following human islet transplantation and increasing β-cells in patients with diabetes.A central focus of research in the type 1 diabetes (T1D) field is to develop ways to safely improve β-cell survival and function and promote their replication. The addition of γ-aminobutyric acid (GABA) or the GABA_B receptor (GABA_B-R)–specific agonist baclofen to culture media has been shown to inhibit β-cell apoptosis in cultured rodent cell lines and islets (1,2). It remains to be determined whether GABA treatment can inhibit mouse β-cell apoptosis in vivo or, more importantly, whether it can protect human β-cells from stress-induced apoptosis. If GABA can inhibit human β-cell apoptosis, elucidating whether this effect is mediated through the G-protein–coupled GABA_B-Rs, and/or the chloride channel GABA_A-Rs will enable more specific drug targeting.GABA can promote neurogenesis and neuronal proliferation and is a neuronal survival factor (3–8). GABA has also been shown to promote rodent β-cell replication (1,2). Those studies, however, differentially pointed to GABA_A-Rs or GABA_B-Rs as modulators of GABA’s effects, making it important to clarify whether one or both types of GABA receptors modulate rodent β-cell replication. While a number of mitogens and growth factors can promote rodent β-cell replication, most fail to promote human β-cell replication (reviewed in refs. 9,10). Therefore, a key question is whether GABA can promote human β-cell replication. Even a small amount of GABA-induced human β-cell replication may be clinically useful by lowering insulin requirements and reducing the risk for long-term complications in T1D patients (11).     

Increased expression of chondroitin sulphate proteoglycans in rat hepatocellular carcinoma tissues

AIM: To investigate the expression of chondroitin sulphate proteoglycans (CSPGs) in rat liver tissues of hepatocellular carcinoma (HCC).METHODS: Thirty male Sprague Dawley rats were randomly divided into two groups: control group (n = 10) and HCC model group (n = 20). Rats in the HCC model groups were intragastrically administrated with 0.2% (w/v) N-diethylnitrosamine (DEN) every 5 d for 16 wk, whereas 0.9% (w/v) normal saline was administered to rats in the control group. After 16 wk from the initiation of experiment, all rats were killed and livers were collected and fixed in 4% (w/v) paraformaldehyde. All tissues were embedded in paraffin and sectioned. Histological staining (hematoxylin and eosin and Toluidine blue) was performed to demonstrate the onset of HCC and the content of sulphated glycosaminoglycan (sGAG). Immunohistochemical staining was performed to investigate the expression of chondroitin sulphate (CS)/dermatan sulphate (DS)-GAG, heparan sulphate (HS)-GAG, keratan sulphate (KS)-GAG in liver tissues. Furthermore, expression and distribution of CSPG family members, including aggrecan, versican, biglycan and decorin in liver tissues, were also immunohistochemically determined.RESULTS: After 16 wk administration of DEN, malignant nodules were observed on the surface of livers from the HCC model group, and their hepatic lobule structures appeared largely disrupted under microscope. Toluidine blue staining demonstrated that there was an significant increase in sGAG content in HCC tissues when compared with that in the normal liver tissues from the control group [0.37 ± 0.05 integrated optical density per stained area (IOD/area) and 0.21 ± 0.01 IOD/area, P < 0.05]. Immunohistochemical studies demonstrated that this increased sGAG in HCC tissues was induced by an elevated expression of CS/DS (0.28 ± 0.02 IOD/area and 0.18 ± 0.02 IOD/area, P < 0.05) and HS (0.30 ± 0.03 IOD/area and 0.17 ± 0.02 IOD/area, P < 0.01) but not KS GAGs in HCC tissues. Further studies thereby were performed to investigate the expression and distribution of several CSPG components in HCC tissues, including aggrecan, versican, biglycan and decorin. Interestingly, there was a distinct distribution pattern for these CSPG components between HCC tissues and the normal tissues. Positive staining of aggrecan, biglycan and decorin was localized in hepatic membrane and/or pericellular matrix in normal liver tissues; however, their expression was mainly observed in the cytoplasm, cell membranes in hepatoma cells and/or pericellular matrix within HCC tissues. Semi-quantitative analysis indicated that there was a higher level of expression of aggrecan (0.43 ± 0.01 and 0.35 ± 0.03, P < 0.05), biglycan (0.32 ± 0.01 and 0.25 ± 0.01, P < 0.001) and decorin (0.29 ± 0.01 and 0.26 ± 0.01, P < 0.05) in HCC tissues compared with that in the normal liver tissues. Very weak versican positive staining was observed in hepatocytes near central vein in normal liver tissues; however there was an intensive versican distribution in fibrosis septa between the hepatoma nodules. Semi-quantitative analysis indicated that the positive rate of versican in hepatoma tissues from the HCC model group was much higher than that in the control group (33.61% and 21.28%, P < 0.05). There was no positive staining in lumican and keratocan, two major KSPGs, in either normal or HCC liver tissues.CONCLUSION: CSPGs play important roles in the onset and progression of HCC, and may provide potential therapeutic targets and clinical biomarkers for this prevalent tumor in humans.     

Quality of life of low vision patients: a systematic review and meta-analysis

ObjectiveQuality of vision plays an important role in everyday living, and low vision (LV) can take a toll on individual's quality of life (QOL). The objective of this paper is to evaluate the impact of LV on QOL and depressive symptoms in LV patients compared with healthy controls.DesignSystematic review and meta-analysis.MethodsLiterature was systematically searched to obtain all relevant records. Covidence software was used to conduct the systematic review. Duplicate records were removed, and 2 independent reviewers screened records for relevance. After screening, risk of bias assessment was carried out. Data were extracted and meta-analysis was performed using STATA 15.0. Fixed-effect and random-effect models were computed based on heterogeneity.ResultsIn total, 2870 records were retrieved from database and grey literature searches. Twelve articles (35 341 subjects) were included for quantitative analysis. Overall, the QOL of LV patients was significantly lower compared with healthy individuals. Common QOL questionnaires, including 25-item visual function questionnaire (VFQ-25) (standard mean difference [SMD] = 0.91, confidence interval [CI]: [0.42–1.40]), 36-item short form survey (SMD = 0.53, CI: [0.26–0.80]), VFQ-14 (SMD = 0.58, CI: [0.42–0.74]), and visual function QOL questionnaire (SMD = 0.68, CI: [0.54–0.82]), demonstrated a poor QOL in LV patients compared with healthy controls. Additionally, odds of depressive symptoms were significantly greater (odds ratio = 2.25, CI: [1.58–3.21]) in LV patients compared with controls.ConclusionLV patients demonstrated a poor QOL and higher odds of depressive symptoms compared with healthy controls.     

年龄相关性白内障患者14万例角膜前表面散光的分布特征

目的分析中国18家医院的14万例年龄相关性白内障患者角膜前表面散光的分布特征。方法回顾性系列病例研究。连续性收集2015年7月至2018年10月于中国18家爱尔眼科医院就诊的40岁以上年龄相关性白内障患者143889例(143889只右眼)的眼部生物学参数资料。角膜前表面散光度数和轴向、前房深度、角膜屈光力、眼轴长度等眼球参数采用IOLMaster 500测量,获取3次测量结果的平均值。各医院将资料整理分析后提交给武汉爱尔眼科医院进行总体分析。非正态分布数据以M(P25~P75)表示;采用Mann-Whitney检验、Kruskal-Wallis检验、χ²检验等分析角膜前表面散光度数和轴向在不同性别、年龄、前房深度、角膜屈光力、眼轴长度中的分布差异。结果143889例患者中女性84319例,男性59570例;年龄为72(65~78)岁;角膜散光度数为0.84(0.51~1.33)D,散光度数≥0.75 D者80895例(56.22%),散光度数≥1.00 D者57304例(39.83%)。女性角膜散光度数为0.87(0.53~1.37)D,男性为0.82(0.50~1.29)D(U=-14.891);女性顺规散光比例为33.26%(28046/84319),逆规散光比例为49.08%(41385/84319);男性顺规散光比例为34.26%(20408/59570),逆规散光比例为46.91%(27945/59570)(χ²=70.913),差异均有统计学意义(均P<0.05)。随年龄增加,角膜散光度数先由0.94(0.57~1.48)D减少至0.75(0.46~1.18)D,后又增大至1.19(0.74~1.79)D,差异有统计学意义(H=1263.438,P<0.05),变化的转折在61~70岁。随着年龄的增大,顺规散光比例减小[由77.50%(396/511)减少至12.50%(3/24)],逆规散光比例增大[由11.15%(57/511)增大至79.07%(34/43)],斜向散光比例变化不大[17.02%(16/94)至19.92%(245/1230)],分布差异有统计学意义(χ²=10174.496,P<0.05)。前房越浅,角膜散光度数越大,由0.82(0.51~1.31)D增大至1.05(0.61~1.56)D;逆规散光比例越大,由47.32%(60207/127227)增大至51.69%(184/356),差异均有统计学意义(H=409.961,χ2=120.995;均P<0.05)。平均角膜屈光力越大,角膜散光度数越大,由0.80(0.49~1.33)D增大至0.95(0.58~1.53)D;逆规散光比例越小,由52.84%(4963/9392)减小至39.97%(9023/22577),差异均有统计学意义(H=808.562,χ²=752.147;均P<0.05)。不同眼轴长度相比,当眼轴长度>25.00 mm时,角膜散光度数最大,为1.04(0.62~1.65)D;逆规散光比例最大,为49.00%(10964/22376),差异均有统计学意义(H=2071.198,χ²=131.130;均P<0.05)。结论年龄相关性白内障患者角膜前表面散光轴向以逆规散光为主。随着年龄的增大,角膜散光度数有先减小后增加的趋势。65岁为顺规散光向逆规散光变化的转折点。前房越浅,角膜前表面散光度数以及逆规散光比例越大。当眼轴长度>25.00 mm时,角膜前表面散光度数和逆规散光比例最大。     

退行性下睑内翻眼轮匝肌缩短矫正术欠矫原因及修补△

目的 分析退行性下睑内翻眼轮匝肌缩短矫正术欠矫原因,评估再次手术修补的效果。方法 收集2008~2017年我院退行性眼睑内翻行眼轮匝肌缩短矫正手术欠矫病例27例(27眼)。分析欠矫原因,并根据其原因选择相应手术方式,观察再次矫正的手术效果。结果 退行性眼睑内翻原因和修补方式为:下睑缩肌断裂未修补15例,给予下睑缩肌修复;水平松弛未矫正7例,给予外眦韧带缩短手术;5例同时存在下睑缩肌断裂和水平松弛,行下睑缩肌修复联合外眦韧带缩短手术。再次手术随访时间内[(18.74±12.11)个月]所有患者症状消失,眼睑位置正常。结论 退行性眼睑内翻眼轮匝肌缩短手术欠矫的原因为手术方式选择不完全正确,眼睑退行性改变因素未得到充分矫正。发生欠矫时,应仔细分析其原因,选择合适的手术方式,仍可以获得良好的矫正效果。     

Segmental and metrical complexity during non-word repetition in adults who stutter

Non-word repetition is weaker for adults who stutter (AWS) compared to adults who do not stutter (AWNS) as phonological demands increase. However, non-word stimuli used in previous studies varied by length, but did not vary with regard to segmental or metrical complexity. The purpose of the present study was to examine the unique influence of these two distinct types of complexity on non-word repetition in AWS and AWNS via administration of the Test of Phonological Structure (TOPhS). Twenty-four adults (12 AWNS, 12 AWS) repeated 96 non-words within a soundproof booth immediately after auditory presentation. All 96 non-word targets included on the TOPhS were one to four syllables in length and ranked based on segmental complexity (simple, moderate and complex) and metrical complexity (simple, moderate and complex). No main effect of metrical complexity was detected between groups, and no differences in accuracy were observed for non-words with simple or moderate segmental complexity. However, AWS were significantly more likely to produce a phonemic error when repeating words with complex segmental structure than AWNS, irrespective of metrical complexity. Segmental complexity may contribute to the differences in phonological working memory in AWS when controlling for metrical complexity and length.