0.05% atropine on control of myopia progression in Chinese school children: a randomized 3-year clinical trial.

AIM: To evaluate the effect of 0.05% atropine on the control of myopia for 2y (phase I) and on spherical equivalent refraction (SER) progression for 1y (phase II) after its withdrawal in Chinese myopic children. METHODS: Totally 142 children with myopia were randomly assigned to the 0.05% atropine group or to the placebo group. In phase I, children received 1 treatment for each eye daily. In phase II, the patients received no treatment. Axial length (AL), SER, intraocular pressure (IOP) and atropine-related side effects were assessed at 6 months' intervals. RESULTS: During phase I, the mean change of SER was -0.46±0.30 D in the atropine group, compared to -1.72±1.12 D in the placebo group (P<0.001). The mean change of AL in the atropine group (0.26±0.30 mm) was significantly shorter than that in the placebo group (0.76±0.62 mm, P=0.002). In addition, in phase II (12mo after the withdrawal of atropine), there was no significant difference in AL change from the atropine group, when compared with that from the placebo group (0.31±0.25 mm vs 0.28±0.26 mm, P>0.05). Furthermore, the change in SER from the atropine group was 0.50±0.41 D, which was significantly lower than 0.72±0.60 D from placebo group, (P<0.05). Finally, there were no statistically significant differences in IOP between the treatment and control groups at any stages (all P>0.05). CONCLUSION: The use of 0.05% atropine for two consecutive years may effectively control elongation of AL and thus progression of myopia, without significant SER progression 1y after atropine withdrawal. Therefore, treatment with 0.05% atropine daily for 2y is effective and safe.

Rational Design of High-Performance Donor-Linker-Acceptor Hybrids Using a Schiff Base for Enabling Photoinduced Electron Transfer.

Donor-linker-acceptor (D-L-A)-based photoinduced electron transfer (PET) has been frequently used for the construction of versatile fluorescent chemo/biosensors. However, sophisticated and tedious processes are generally required for the synthesis of these probes, which leads to poor design flexibility. In this work, by exploiting a Schiff base as a linker unit, a covalently bound D-L-A system was established and subsequently utilized for the development of a PET sensor. Cysteamine (Cys) and N-acetyl-l-cysteine (NAC) costabilized gold nanoclusters (Cys/NAC-AuNCs) were synthesized and adopted as an electron acceptor, and pyridoxal phosphate (PLP) was selected as an electron donor. PLP can form a Schiff base (an aldimine) with the primary amino group of Cys/NAC-AuNC through its aldehyde group and thereby suppresses the fluorescence of Cys/NAC-AuNC. The Rehm-Weller formula results and a HOMO-LUMO orbital study revealed that a reductive PET mechanism is responsible for the observed fluorescence quenching. Since the pyridoxal (PL) produced by the acid phosphatase (ACP)-catalyzed cleavage of PLP has a weak interaction with Cys/NAC-AuNC, a novel turn-on fluorescent method for selective detection of ACP was successfully realized. To the best of our knowledge, this is the first example of the development of a covalently bound D-L-A system for fluorescent PET sensing of enzyme activity based on AuNC nanoprobes using a Schiff base.

Overexpression of Tripartite Motif-Containing 48 (TRIM48) Inhibits Growth of Human Glioblastoma Cells by Suppressing Extracellular Signal Regulated Kinase 1/2 (ERK1/2) Pathway.

BACKGROUND Herein, we found that tripartite motif-containing 48 (TRIM48) was reduced in human glioblastoma (GBM) cell lines. We investigated whether and how TRIM48 functions in human GBM in vitro. MATERIAL AND METHODS Human GBM cells (U87 MG and U138 MG) were infected with lentivirus to overexpress TRIM48, and 1 human GBM cell line (T98G) was infected with siRNAs to knock down TRIM48 expression. Techniques used included cell proliferation assay, measured by CCK-8 and BrdU-ELISA method, and cell cycle assay, determined using flow cytometry. Curcumin, a specific activator of extracellular signal regulated kinases (ERK1/2), or PD98059, a specific inhibitor of ERK1/2, was used to activate or block the ERK1/2 pathway, respectively. Expression of phosphorylated (p)-ERK1/2, and its downstream targets (Cyclin D1) were measured to assess the mechanism. RESULTS Our data suggest that overexpression of TRIM48 reduces the viability of U87 MG and U138 MG and leads to cell cycle arrest (in G0-G1 phase), which is associated with blockade of the ERK1/2 pathway and reduction of Cyclin D1. In contrast, knockdown of TRIM48 resulted in the opposite effects. Interestingly, the inhibitory effect of TRIM48 overexpression on human GBM cell growth and the inactivation of ERK1/2 were significantly alleviated with additional curcumin treatment, while it the promoted the effect of siTRIM48 on human GBM cell growth, and the activation of ERK1/2 was significantly alleviated with additional PD98059 treatment. CONCLUSIONS TRIM48 suppressed the growth of human GBM cell via the prevention of ERK1/2 activation.

Rg1 inhibits high glucose-induced mesenchymal activation and fibrosis via regulating miR-2113/RP11-982M15.8/Zeb1 pathway.

Recent study has showed that Ginsenoside Rg1, the mian active compound of Panax ginseng, could ameliorate oxidative stress and myocardial apoptosis in diabetes mellitus. However, the roles and mechanisms of Rg1 in proliferative diabetic retinopathy (PDR) are still unclear. In the present study, we aimed to investigate the effects of Rg1 on mesenchymal activation of high-glucose (HG) cultured müller cells. High glucose conditions up-regulate MMP-2, MMP-9 and down-regulate TIMP-2, and promote mesenchymal activation in Müller cells. And Rg1 inhibits the HG-induced mesenchymal activation and HG-increased MMP-2 and MMP-9 and HG-decreased TIMP-2 in Müller cells. HG up-regulates Zeb1 and lncRNA RP11-982M15.8, and down-regulates miR-2113, and Rg1 inhibits these effects of HG. Both inhibition of miR-2113 and over-expression of RP11-982M15.8 significantly restored the HG induced mesenchymal activasion. Taken together, our findings suggested that Rg1 inhibited HG-induced mesenchymal activation and fibrosis via regulating miR-2113/RP11-982M15.8/Zeb1 pathway.

MiR-126 overexpression inhibits high glucose-induced migration and tube formation of rhesus macaque choroid-retinal endothelial cells by obstructing VEGFA and PIK3R2.

AIM: The aims of this study are to investigate the relative regulation between miR-126 and VEGF/PI3K/AKT signaling pathway in retinal vascular endothelial cells. METHODS: Rhesus macaque choroid-retinal endothelial cell line (RF/6A) cells were cultured in high glucose to imitate the conditions occurring in DR. First, we detected the expression of miR-126, VEGFA and PIK3R2 in RF/6A cells on the condition of high glucose by q-PCR and western blot. Then, after addition of miR-126 mimics and miR-126 inhibitor, we investigated the function of miR-126 in RF/6A cells by scratch wound, Transwell migration and tube formation assays, and the effect of miR-126 on the expression of VEGFA, PIK3R2 and AKT. Moreover, bioinformatics analysis and luciferase array were used to confirm the direct or specific regulation of miR-126 to VEGFA or PIK3R2. RESULTS: Here, first, we found that high glucose could induce the decrease of miR-126 and the increase of VEGFA and PIK3R2 in RF/6A. Then, by scratch wound, Transwell migration and tube formation assays, we found that miR-126 overexpression could inhibit the migration and sprouting of RF/6A cells induced by high glucose, while knockdown of miR-126 led to the opposite results. Moreover, overexpression of miR-126 inhibited the increased expression of VEGFA, PIK3R2, SDF-1α, VCAM-1, and SPRED1, and the activation of AKT1 induced by high glucose and miR-126 inhibitor caused the opposite results which were determined by q-PCR and western blot. In addition, by luciferase assay, we found that miR-126 could directly negatively regulate VEGFA and PIK3R2. CONCLUSION: Our results suggest that miR-126 overexpression inhibits the migration and sprouting of RF/6A cells induced by high glucose which might possibly be by blocking VEGFA and PIK3R2 in the VEGF/PI3K/AKT signaling pathway.

Gene-gene interaction of GJB2, SOD2, and CAT on occupational noise-induced hearing loss in Chinese Han population.

The effects of genetic factors on the noise-induced hearing loss (NIHL) are still unclear. In the present study, eight single-nucleotide polymorphisms (SNPs) included rs1227049 and rs3802711 (CDH23), rs1695 (GSTP1), rs137852540 (GJB2), rs2289274 (PMCA2), rs4880 (SOD2), rs7943316, and rs769214 within CAT that might associated with NIHL were further validated in Chinese workers. The results showed that the carriers of the T allele (AT+TT) of rs7943316 and A allele (GA+AA) of rs769214, were significantly associated with an increased risk of NIHL compared to those with AA genotype (P<0.05) and GG genotype (P<0.05). Moreover, a significant three-locus model (P=0.0107) involving rs2016520, rs9794, and rs1805192 were observed that might associated with NIHL, with 53.95% of testing accuracy. Thus, our present study provided the evidence that GJB2, SOD2, and CAT genes might account for the NIHL development in independently and/or in an interactive manner.

Multi-slice computed tomography manifestations of hepatic epithelioid angiomyolipoma.

AIM: To explore the characteristics of multi-slice computed tomography (CT) manifestations of hepatic epithelioid angiomyolipoma (HEA), improve the rate of accurate diagnosis, and reduce the misdiagnostic rate. METHODS: The multi-slice CT manifestations in five patients who were diagnosed with HEA definitely by postoperative pathological examination were analysed retrospectively. Three female patients and two male patients were included. Before operation, four patients received plain CT scanning and dynamic enhancement scanning, and the other patient only received enhancement scanning, with immunohistochemical analysis conducted after postoperative pathological examination. Four patients were misdiagnosed by CT, including three patients misdiagnosed with hepatic cell carcinoma and one patient with focal nodular hyperplasia. RESULTS: Upper abdominal multi-slice spiral CT scanning and three-stage enhancement scanning were conducted in five patients with HEA before operation. HEA had certain characteristic CT manifestations: low density masses, a few relatively high-density masses or fat-density masses diffusely shown in foci, clear boundary, round or oval and large focus, and tumour size ranging from 3.1 cm × 2.5 cm to 7.0 cm × 5.2 cm. During enhancement scanning, the foci were significantly enhanced uniformly or non-uniformly during the arterial phase, while during the venous and equilibrium phases, the foci were enhanced continuously or showed obvious low-density masses. Obviously enhanced and widened vessels could be found adjacent to foci or in the central area of foci during the arterial phase. CONCLUSION: CT manifestations of HEA have certain characteristics. Primary diagnosis can be obtained by combining CT findings with clinical data, but pathological examination is still needed for a definite diagnosis.

The structural diversity and photoluminescent properties of cadmium thiophenedicarboxylate coordination polymers.

Two series of Cd(II) coordination polymers (CPs), {[Cd(bimm)2(H2O)2][(3,4-tdc)2][H2O]2}n (1a), [Cd(3,4-tdc)(bimb)]n (2a), [Cd(3,4-tdc)(bimpy)(H2O)]n (3a) and [Cd(2,3-Htdc)2(bimm)2]n (1b), {[Cd(2,3-tdc)(bimb)](H2O)}n (2b), [Cd(2,3-tdc)(bimpy)(H2O)]n (3b) where H2tdc = thiophenedicarboxylic acid, bimm = 1,2-bis(imidazol-1'-yl)methane, bimb = 1,2-bis(imidazol-1'-yl)butane and bimpy = 3,5-bis(imidazol-1'-yl)pyridine, have been synthesized by using Cd(II) acetate with H2tdc and N-donor ligands under hydrothermal conditions. Two related isomeric thiophenedicarboxylic acids were chosen to examine the positional isomeric effect on the construction of these CPs with distinct dimensionality and connectivity. The structure of 1a is a one-dimensional (1D) cationic double chain further forming a two-dimensional (2D) supramolecular network via hydrogen-bonding interactions, while 1b exhibits a neutral double chain structure. Interestingly, a three-dimensional (3D) 4-connected cds network for 2a as well as a 1D neutral double chain structure for 2b were obtained in the presence of bimb. When the rigid tripodal bimpy was introduced, isomorphous 3a and 3b with 3D (3,5)-connected (6(2)·8) (6(7)·8(3)) nets were constructed. The structural diversity of 1a-2b mainly stems from the positional isomeric effect of thiophenedicarboxylate, while 3a and 3b are well regulated by rigid bimpy. Moreover, the thermal stability and photoluminescence of 1a-3b are investigated.

Application value of multi-slice spiral computed tomography for imaging determination of metastatic lymph nodes of gastric cancer.

AIM: To evaluate the application value of multi-slice spiral computed tomography (MSCT) for imaging determination of metastatic lymph nodes of gastric cancer and to explore reasonable diagnostic criteria. METHODS: Sixty patients with gastric cancer underwent 64 MSCT scans before operation. Gastric cancer samples and perigastric lymph nodes were obtained after operation, formalin fixation and haematoxylin-eosin staining. The metastatic conditions of gastric cancer and perigastric lymph nodes were determined under a light microscope. A total of 605 lymph nodes were grouped and assessed according to distribution, size, shape and degree of lymph node enhancement. Then, the findings were compared with the postoperative pathological results. RESULTS: Among 605 lymph nodes, 358 were confirmed as metastatic, accounting for 59.2%. A total of 535 lymph nodes were detected in original axis images combined with multiplanar reconstruction images of MSCT. The metastatic lymph nodes had specific signs in computed tomography. This study showed that the long diameter of lymph nodes ≥ 8 mm indicated metastasis; the sensitivity and specificity were 79.6% and 78.8%, respectively. The difference of the mean value of lymph node enhancement density ≥ 80 Hu indicated metastasis; the sensitivity and specificity were 81.6% and 75.6%, respectively. The ratio of short diameter to long diameter of lymph nodes ≥ 0.7 indicated metastasis; the sensitivity and specificity were 85.6% and 71.8%, respectively. CONCLUSION: MSCT is a non-invasive and reliable method for preoperative examination of gastric cancer. Sensitivity and specificity for prediction of lymph node metastasis are high.

2-Iodo-1,3-dimethoxy-benzene.

Crystals of the title compound, C(8)H(9)IO(2), were obtained from a dimethyl sulfoxide solution of 2,6-dimethoxy-benzoic acid and iodo-benzene diacetate under a nitro-gen atmosphere at 353 K. In the crystal structure, mol-ecules are linked by weak C-H⋯π inter-actions, generating inter-penetrating one-dimensional chains of perpendicularly oriented mol-ecules extending along [011] and [01]. Chains are also formed through non-bonding C-I⋯π contacts extending in the same directions, projecting a zigzag motif in view down [100]. The I⋯Cg distance is 3.695 (2) Šand the C-I⋯Cg angle is 164.17 (14)°. The mol-ecular symmetry m coincides with the mirror plane of the space group Cmc2(1), resulting in a half-mol-ecule in the asymmetric unit (Z' = ½).

Adamantyl-substituted retinoid-derived molecules that interact with the orphan nuclear receptor small heterodimer partner: effects of replacing the 1-adamantyl or hydroxyl group on inhibition of cancer cell growth, induction of cancer cell apoptosis, and inhibition of SRC homology 2 domain-containing protein tyrosine phosphatase-2 activity.

(E)-4-[3-(1-Adamantyl)-4'-hydroxyphenyl]-3-chlorocinnamic acid (3-Cl-AHPC) induces the cell-cycle arrest and apoptosis of leukemia and cancer cells. Studies demonstrated that 3-Cl-AHPC bound to the atypical orphan nuclear receptor small heterodimer partner (SHP). Although missing a DNA-binding domain, SHP heterodimerizes with the ligand-binding domains of other nuclear receptors to repress their abilities to induce or inhibit gene expression. 3-Cl-AHPC analogues having the 1-adamantyl and phenolic hydroxyl pharmacophoric elements replaced with isosteric groups were designed, synthesized, and evaluated for their inhibition of proliferation and induction of human cancer cell apoptosis. Structure-anticancer activity relationship studies indicated the importance of both groups to apoptotic activity. Docking of 3-Cl-AHPC and its analogues to an SHP computational model that was based on the crystal structure of ultraspiracle complexed with 1-stearoyl-2-palmitoylglycero-3-phosphoethanolamine suggested why these 3-Cl-AHPC groups could influence SHP activity. Inhibitory activity against Src homology 2 domain-containing protein tyrosine phosphatase 2 (Shp-2) was also assessed. The most active Shp-2 inhibitor was found to be the 3'-(3,3-dimethylbutynyl) analogue of 3-Cl-AHPC.