Assessing the benefits of multisensory audiotactile stimulation for overweight individuals

We report an experiment designed to examine whether individuals who are overweight would perform differently when trying to detect and/or discriminate auditory, vibrotactile, and audiotactile targets. The vibrotactile stimuli were delivered either to the participant’s abdomen or to his hand. Thirty-six young male participants were classified into normal, underweight, or overweight groups based on their body mass index. All three groups exhibited a significant benefit of multisensory (over the best of the unisensory) stimulation, but the magnitude of this benefit was modulated by the weight of the participant, the task, and the location from which the vibrotactile stimuli happened to be presented. For the detection task, the overweight group exhibited a significantly smaller benefit than the underweight group. In the discrimination task, the overweight group showed significantly more benefits than the other two groups when the vibrotactile stimuli were delivered to their hands, but not when the stimuli were delivered to their abdomens. These results might raise some interesting questions regarding the mechanisms underlying audiotactile information processing and have applied relevance for the design of the most effective warning signal (e.g., for drivers).     

Gram-scale synthesis of nitrogen doped graphene quantum dots for sensitive detection of mercury ions and l-cysteine

Sensitive and reliable detection of mercury ions (Hg²⁺) and l-cysteine (l-Cys) is of great significance for toxicology assessment, environmental protection, food analysis and human health. Herein, we present gram-scale synthesis of nitrogen doped graphene quantum dots (N-GQDs) for sensitive detection of Hg²⁺ and l-Cys. The N-GQDs are one-step synthesized using bottom-up molecular fusion in a hydrothermal process with gram-scale yield at a single run. N-GQDs exhibit good structural characteristics including uniform size (∼2.1 nm), high crystallinity, and single-layered graphene thickness. Successful doping of N atom enables bright blue fluorescence (absolute photoluminescence quantum yield of 24.8%) and provides unique selectivity towards Hg²⁺. Based on the fluorescence quenching by Hg²⁺ (turn-off mode), N-GQDs are able to serve as an effective fluorescent probe for sensitive detection of Hg²⁺ with low limit of detection (19 nM). As l-Cys could recover the fluorescence of N-GQDs quenched by Hg²⁺, fluorescent detection of l-Cys is also demonstrated using turn-off-on mode.

One-step and gram-scale synthesis of nitrogen doped graphene quantum dots is realized for their sensitive detection of Hg²⁺ and l-Cys.     

Design,synthesis, and biological evaluation of thieno[3,2‐d]pyrimidine derivatives as potential simplified phosphatidylinositol 3‐kinase alpha inhibitors

A series of thieno[3,2‐d]pyrimidine derivatives as phosphatidylinositol 3‐kinase (PI3K) inhibitors was designed using the combination strategy. The synthesis and biological evaluation of the derivatives demonstrated their potent inhibition of PI3K, culminating in the discovery of 7 and 21 . Determination of a co‐crystal structure of 7 complexed with PI3Kα provided the structural basis for the high enzymatic activity. Furthermore, cellular investigation of compounds 7 and 21 revealed that they efficiently suppressed cancer cell lines proliferation through inhibition of intracellular PI3K/AKT/mammalian target of rapamycin pathway. The results provided potent simplified inhibitors of PI3K with a promising overall profile and a chemical series for further optimization to progress into vivo experiments.     

基于YOLO算法和ResNet深度卷积神经网络的结直肠息肉检测（含视频）

目的 构建一个基于YOLO算法和ResNet网络的自动检测结直肠息肉的深度卷积神经网络（deep convolutional neural network,DCNN）模型,并测试其功能。 方法 选取武汉大学人民医院消化内镜中心数据库2018年1月—2019年3月的肠镜图像及视频并分为3个数据集（数据集1、3、4）,另以公共数据集CVC-ClinicDB（由西班牙巴塞罗那医院提供的29个结肠镜检查视频中提取的612帧息肉图像组成）作为数据集2。数据集1（2018年1—11月的肠息肉图像3 700张,无息肉图像1 000张）用于DCNN模型构建、训练与验证;数据集2和数据集3（2019年1—3月的肠息肉图像320张,无息肉图像400张）用于DCNN模型在图像中的测试;数据集4（2018年12月肠镜视频15个,包含33个息肉）,用于DCNN模型在视频中的测试。主要观察DCNN模型检测肠息肉的敏感度、特异度、准确率和假阳性率。 结果 DCNN模型在数据集2中检测肠息肉的敏感度为93.19%（602/646）;在数据集3中检测肠息肉的准确率为95.00%（684/720）,敏感度为98.13%（314/320）,特异度为92.50%（370/400）,假阳性率为7.50%（30/400）;在数据集4中检测息肉逐息肉个数的敏感度为100.00%（33/33）,逐帧准确率为96.29%（133 840/138 998）,逐帧敏感度为90.24%（4 066/4 506）,逐帧特异度为96.49%（129 774/134 492）,逐帧假阳性率为3.51%（4 718/134 492）。 结论 构建的DCNN模型可用于自动检测结直肠息肉,在静止肠镜图像及肠镜视频中均具有较高的敏感度与特异度,且在视频中测试的假阳性率低,可用于帮助内镜医师检测结直肠息肉。     

Cryptotanshinone ameliorates renal ischaemia–reperfusion injury by inhibiting apoptosis and inflammatory response

Cryptotanshinone (CTS) is a natural compound from the Chinese herb Salvia miltiorrhiza. Previous studies demonstrated that CTS possesses anti‐apoptotic and anti‐inflammatory properties. However, its effects and underlying mechanism on renal ischaemia reperfusion (IR) injury remain unknown. In the present study, we investigated the effects of CTS on renal IR injury and its potential underlying mechanisms. Mice were randomized into four groups as follows: (a) sham operation + vehicle, (b) sham operation + CTS, (c) IR + vehicle, (d) IR + CTS. The CTS‐treated group were injected intraperitoneally with CTS (10 mg/kg/d) for 7 days prior to IR operation. Renal IR injury was induced by clamping the bilateral renal artery for 30 minutes followed by 24 hours of reperfusion. The mice were then killed to collect the serum and the kidneys for analysis. The results of the present study showed that CTS pretreatment significantly attenuates IR‐induced renal functional and morphological injuries, which was accompanied with inhibition of cell apoptosis and inflammatory response. Moreover, the phosphorylation of p38 mitogen‐activated protein kinase (MAPK) and the activation of nuclear factor‐κB (NF‐κB) signalling were inhibited by CTS. Therefore, CTS could be a useful therapeutic agent in the fight against renal IR injury.     

脑-星状神经节-心房通路调控巨噬细胞对犬急性脑卒中后心房颤动的影响

目的探讨脑-星状神经节-心房通路对犬急性脑卒中(AS)后心房颤动(房颤)的影响及其调控机制。方法26只比格犬按随机数字表法随机分为假手术组(Sham组,n=6)、急性脑卒中组(AS组,n=7)、星状神经节消融(stellate ganglion ablation)组(SGA组,n=6)和巨噬细胞清除组(CL组,n=7)。Sham组犬开颅手术后不行大脑中动脉阻塞(middle cerebral artery occlusion,MCAO);AS组行MCAO后建立AS模型;SGA组行MCAO后行左侧星状神经节(LSG)消融;CL组行MCAO后于左、右心房注射磷酸二钠脂质体。4组犬于3 d后记录心房有效不应期(ERP)、有效不应期离散度(dERP)、房颤诱发率、交感神经活性、巨噬细胞及相关炎性细胞因子表达水平。结果与Sham组比,AS组心房dERP[(14.8±2.1)ms对(36.5±4.8)ms,P<0.05]和房颤诱发率[(4.4±2.2)%对(24.4±4.4)%,P<0.05]均明显升高,而SGA组与CL组dERP[(36.5±4.8)ms对(21.0±3.6)ms,(17.6±2.8)ms,均P<0.05]和房颤诱发率[(24.4±4.4)%对(5.5±2.7)%,(5.3±3.2)%,均P<0.05]均较AS组显著降低;Sham组、SGA组和CL组间房颤诱发率和巨噬细胞水平差异无统计学意义;AS组和CL组LSG活性均较Sham和SGA组明显增加;AS组巨噬细胞和相关炎性因子浸润明显高于Sham、CL和SGA组。结论脑-星状神经节-心房系统可通过增加心房组织巨噬细胞水平增加AS模型犬房颤的易患性。     

二甲双胍调节糖尿病大鼠心房小电导钙激活钾通道亚型蛋白表达的信号通路

目的探讨蛋白激酶A(PKA)/钙调蛋白Ⅱ(CaMKⅡ)信号通路在二甲双胍(Met)调节2型糖尿病(T2DM)大鼠心房小电导钙激活钾通道亚型KCa2.2和KCa2.3蛋白表达中的作用。方法健康雄性Wistar大鼠40只,随机选8只喂普通饲料为对照组(Con组),另32只喂高脂高糖饲料联合腹腔注射小剂量链脲佐菌素构建T2DM大鼠模型后,再随机分为DM组、Met组、H-89组(腹腔注射PKA抑制剂H-89)和KN-93组(腹腔注射CaMKⅡ抑制剂KN-93),每组8只。用ELISA检测大鼠心房组织PKA活性,qRT-PCR检测CaMKⅡmRNA表达,Western blot和免疫组织化学检测KCa2.2、KCa2.3和磷酸化CaMKⅡ(p-CaMKⅡ)蛋白表达。结果 Con组、DM组、Met组和H-89组PKA活性分别为0.74±0.04、0.50±0.05、0.69±0.03和0.48±0.03。与DM组比较,Met组PKA活性明显提升(P<0.01);与Met组比较,H-89组显著抑制PKA活性(P<0.01)。Con组、DM组及Met组CaMKⅡmRNA分别为1.00±0.07、0.61±0.03和0.92±0.09。与Con组比较,DM组CaMKⅡmRNA表达明显降低(P<0.01);与DM组比较,Met组CaMKⅡmRNA表达明显增加(P<0.01)。与Con组比较,DM组心房组织p-CaMKⅡ和KCa2.2蛋白表达均明显降低,KCa2.3蛋白表达明显升高(P<0.01)。与DM组比较,Met组明显提升p-CaMKⅡ和KCa2.2蛋白表达,明显抑制KCa2.3蛋白表达(P<0.01)。与Met组比较,KN-93组和H-89组分别显著抑制p-CaMKⅡ蛋白表达和PKA活性,均显著下调KCa2.2蛋白表达,上调KCa2.3蛋白表达(P<0.01)。免疫组织化学染色显示,与Met组比较,KN-93组和H-89组均显著下调KCa2.2蛋白表达,上调KCa2.3蛋白表达(P<0.05,P<0.01),与Western blot检测结果一致。结论 Met通过激活PKA/CaMKⅡ信号通路部分修复T2DM大鼠心房KCa2.2蛋白下调和KCa2.3蛋白上调。     

含1,2-苯并噻嗪结构的［1,3,4］噻二唑并［3,2-a］［1,3,5］三嗪衍生物的合成及其抗肿瘤活性

以吡罗昔康合成中间体(CAS:35511-15-0)为原料,利用活性拼接等药物设计原理,设计并合成了9个结构新颖的目标化合物,其结构经¹H NMR、MS等表征。通过测定对胰腺癌细胞Capan-1、白血病细胞L1210和人肝癌细胞SMMC-7721的抑制活性,评价目标化合物的体外抗肿瘤活性。结果表明,化合物6f(IC₅₀=2.4±0.5 μmol/L)对胰腺癌细胞Capan-1表现出较好的抑制活性;化合物6h(IC₅₀=5.4±0.2 μmol/L)对白血病细胞L1210表现出较好的抑制活性;化合物6g(IC₅₀=3.8±0.2 μmol/L)对人肝癌细胞SMMC-7721表现出较好的抑制活性。初步的抗肿瘤活性实验结果表明,将吡罗昔康3位的侧链替代为噻二唑并三嗪侧链,对提高该类化合物的抗肿瘤活性有一定的作用。     

自我效能理论在代谢综合征患者血糖控制中的应用

目的探讨自我效能理论对代谢综合征患者血糖控制的影响。方法选取100例代谢综合征高血糖患者按照随机、开放、对照、平行方法分为对照组与实验组各50例,对照组给予内分泌常规治疗,实验组在常规治疗的基础上进行增强自我效能健康宣教,比较两种方法对患者血糖控制的影响。结果3个月后实验组的自我效能评分、糖化血红蛋白及空腹血糖的控制优于对照组（ P＜0.01或＜0.05）;两组患者餐后2 h血糖控制差异无统计学意义（ P＞0.05）。结论在代谢综合征高血糖患者治疗过程中应用自我效能理论,可以有效改善血糖控制。     

Soluble FGL2, a novel effector molecule of activated hepatic stellate cells,regulates T-cell function in cirrhotic patients with hepatocellular carcinoma

Purpose

To investigate the effects of soluble FGL2 (sFGL2) secreted by hepatic stellate cells (HSCs) on immune suppression in cirrhotic patients with hepatocellular carcinoma (HCC).

Methods

Serum sFGL2 levels were examined by ELISA in 40 patients with HCC, liver cirrhosis (LC) or chronic HBV (CHB) infection. A double staining of the immunofluorescence analysis of α-SMA and FGL2 was performed in two cirrhotic liver specimens. The expression of FGL2 in the LX2 cell line was analyzed by immunofluorescence, Western blot and flow cytometry. T-cells purified from HCC patients using magnetic beads were cultured with LX2 cells at different ratios with anti-CD3-stimulating or FGL2-blocking antibodies. The proliferation index (PI) of CD8 + T cells was assessed by flow cytometry, and the secretion of IFN-γ was measured by ELISA.

Results

sFGL2 levels are significantly higher in patients with HCC or LC compared with those with CHB (p = 0.0039/p = 0.0020). Among HCC patients, those with cirrhosis exhibited significantly higher levels of sFGL2 compared with non-cirrhotic individuals (p = 0.0108). The expressions of FGL2 and α-SMA overlapped in HSCs in liver specimens. FGL2 protein secreted by LX2 cells inhibited T-cell proliferation of HCC patients in a dose-dependent manner in vitro. The PI of CD8 + T cells was significantly enhanced following addition of FGL2 antibody to the culture system (LX2/T-cell ratio of 1:10, p = 0.002). The level of IFN-γ in mixed cultures was inversely correlated with the number of HSCs and was reversed by incubation with FGL2 blocking antibody.

Conclusion

sFGL2 protein is a novel effector molecule of activated HSCs, which suppresses CD8 + T cell proliferation and interferon-γ production, and it subsequently might contribute to immune suppression during fibrosis and tumorigenesis in the liver.