Inhibition of Posterior Capsule Opacification by Adenovirus-Mediated Delivery of Short Hairpin RNAs Targeting TERT in a Rabbit Model.

PURPOSE: Posterior capsule opacification (PCO) is the most common postoperative complication after cataract surgery and cannot yet be eliminated. Here, we investigated the inhibitory effects of telomerase reverse transcriptase (TERT) gene silencing on PCO in a rabbit model. METHODS: After rabbit lens epithelial cells (LECs) were treated with adenovirus containing short hairpin RNAs (shRNA) targeting TERT (shTERT group), adenovirus containing scramble nonsense control shRNA (shNC group) or PBS (control group), quantitative real-time polymerase chain reaction and Western blotting were used to measure the expression levels of TERT, and a scratch assay was performed to assess the LEC migration. New Zealand white rabbits underwent sham cataract surgery followed by an injection of adenovirus carrying shTERT into their capsule bag. The intraocular pressure and anterior segment inflammation were evaluated on certain days, and EMT markers (α-SMA and E-cadherin) were evaluated by Western blotting and immunofluorescence. The telomerase activity of the capsule bag was detected by ELISA. At 28 d postoperatively, hematoxylin and eosin staining of the cornea and iris and electron microscopy of the posterior capsule were performed. RESULTS: Application of shTERT to LECs downregulated the expression levels of TERT mRNA and protein. The scratch assay results showed a decrease in the migration of LECs in the shTERT group. In vivo, shTERT decreased PCO formation after cataract surgery in rabbits and downregulated the expression of EMT markers, as determined by Western blotting and immunofluorescence. In addition, telomerase activity was suppressed in the capsule bag. Despite slight inflammation in the iris, histologic results revealed no toxic effects in the cornea and iris. CONCLUSION: TERT silencing effectively reduces the migration and proliferation of LECs and the formation of PCO. Our findings suggest that TERT silencing may be a potential preventive strategy for PCO.

Evaluation of retinal vessel and perfusion density in migraine patients by optical coherence tomography angiography.

BACKGROUND: Migraine is a neurovascular disease and has been reported as a risk factor for ocular vascular complications. Our study aimed to compare the retinal vessel density and perfusion density between migraine patients and healthy subjects by optical coherence tomography angiography (OCTA). METHODS: In this prospective study, 23 patients with migraine with aura (MWA) and 31 patients with migraine without aura (MWOA), and 32 age- and gender-matched healthy controls (HC) were enrolled. The vessel density (VD) and perfusion density (PD) were evaluated in a 6 × 6 mm scan of the macula and optic nerve head (ONH) with the Cirrus HD-OCT 5000 device. The measurement area is divided into three areas: center (c), inner ring (ir), outer ring (or) (with diameters of 1, 3, and 6 mm respectively), and nine subfields, according to the Early Treatment Retinopathy Study grid. RESULTS: The macular cVD, cPD, and temporal orVD in MWA and MWOA groups were significantly reduced than those of HC. On optic nerve head OCTA, patients with MWA had decreased cVD, average irVD, inferior irVD, and temporal orVD compared with HCs while MWOA had reduced cVD than HC group. In addition, PD was not significantly different among MWA, MWOA, and HC groups in any measure in the optic nerve head. The Migraine Disability Assessment Score (MIDAS) and attack frequency were significantly inversely correlated with cVD, cPD, irVD, and irPD of macula and ONH. CONCLUSIONS: Vessel and perfusion density of macula were reduced in both MWA and MWOA. Vessel density, but not perfusion density of ONH was decreased in MWA. The migraine severity and attack frequency were significantly inversely correlated with vessel and perfusion density of macula and ONH.

Dynamic Programming BN Structure Learning Algorithm Integrating Double Constraints under Small Sample Condition.

The Bayesian Network (BN) structure learning algorithm based on dynamic programming can obtain global optimal solutions. However, when the sample cannot fully contain the information of the real structure, especially when the sample size is small, the obtained structure is inaccurate. Therefore, this paper studies the planning mode and connotation of dynamic programming, restricts its process with edge and path constraints, and proposes a dynamic programming BN structure learning algorithm with double constraints under small sample conditions. The algorithm uses double constraints to limit the planning process of dynamic programming and reduces the planning space. Then, it uses double constraints to limit the selection of the optimal parent node to ensure that the optimal structure conforms to prior knowledge. Finally, the integrating prior-knowledge method and the non-integrating prior-knowledge method are simulated and compared. The simulation results verify the effectiveness of the method proposed and prove that the integrating prior knowledge can significantly improve the efficiency and accuracy of BN structure learning.

A rare asymptomatic metallic intraocular foreign body retained in the anterior chamber for 15 years: A case report.

RATIONALE: Intraocular foreign bodies (IOFBs) are common in ocular injuries, but asymptomatic metallic IOFBs retained in the anterior chamber for years are rare. PATIENT CONCERNS: A 31-year-old female presented with blurred vision in her right eye after lumbar magnetic resonance imaging. Her best-corrected vision acuity was 0.6 in the right eye and 1.0 in the left eye. Slit-lamp examination revealed a brown granular foreign body in the anterior chamber and pigmentation of the limbus. Lens and retina examination indicated ocular siderosis. Corneal endothelioscopy revealed decreased endothelial cell density. A detailed history showed ocular globe injury 15 years earlier. DIAGNOSES: Anterior chamber IOFB with ocular siderosis. INTERVENTIONS: Anterior chamber foreign body removal was performed with appropriate incision and forceps. OUTCOMES: The anterior chamber IOFB was successfully removed and examined as a magnetic metal foreign body. The best-corrected vision acuity was 1.0 at 1 day postoperatively. An abnormal electroretinogram with a 12% decrease in the "b" wave and a 91% decrease in the "a" wave was observed 3 months postoperatively. There were no intraoperative or postoperative complications during a 3-month follow-up. LESSONS: Eye trauma should be examined carefully to exclude IOFBs. Asymptomatic anterior chamber foreign bodies can also cause corneal endothelial injury and ocular siderosis. Careful examination and timely management are needed in such cases.

Polysaccharides extracted from Cassia seeds protect against high glucose-induced retinal endothelial cell injury.

INTRODUCTION: To investigate the protect effect of polysaccharides extract from cassia seeds (CSPE) on human retinal endothelial cells (HRECs) in hyperglycemia environment. METHODS: The same amount of human retinal endothelial cells (HRECs), respectively, inoculated in vitro were divided into normal group (Con group), hyperglycemia group (H-Glu group), and different concentration of cassia polysaccharides extract (CSPE) combined with high glucose medium group (CSPE group). HRECs in Con group were cultured routinely. The cell in H-Glu group was treated with high glucose, in which the concentration of glucose in the medium was 30 mM. HRECs in CSPE group were treated with different concentrations of CSPE combined with high glucose. Enhanced cell counting kit-8(CCK8) assay was used to measure the HRECs cell survival rate in different groups. The generation of reactive oxygen species (ROS) in different group was measured by flow cytometry. The real-time quantitative PCR analysis was used for determining intracellular heme oxygenase-1 (HO-1) mRNA levels. Western Blot was applied to test the change of proteins, such as HO-1- and NF-E2-related factor 2 (Nrf2) protein. RESULTS: The cell survival rate of the H-Glu group was significantly lower than that of the Con group (P < 0.05). When the concentration of CSPE was 100 mg/ml in CSPE group, the HRECs cell survival rate was significantly lower than that of the Con group (P < 0.05), and there was no significant difference with H-Glu group. When the concentration of CSPE in CSPE group was between 50 µg/ml and 1 × 104 µg/ml, the survival rate of HRECs cells showed no significant difference compared with that of H-Glu group and Con group. However, when the concentration of CSPE in CSPE group was between 2.5 and 40 µg/ml, the HRECs cell survival rate was significantly higher than that of H-Glu group (P < 0.05) with a concentration-independent, and there was no significant difference between CSPE group and Con group. The ROS production was lowest in the CSPE group and was lower in Con group than in the H-Glu group. The contents of HO-1 mRNA (P < 0.05), HO-1 and Nrf2 protein were lower in the H-Glu group than in the CSPE and Con group, and there was no significant difference between the CSPE group and H-Glu group. CONCLUSIONS: A certain concentration range of CSPE can increase the expression of the downstream protein HO-1 and negatively regulate the production of ROS by upregulating the expression of Nrf2, thus protecting human retinal endothelial cells from oxidative damage caused by high glucose.

Effect of Electroacupuncture on Postoperative Gastrointestinal Recovery in Patients Undergoing Thoracoscopic Surgery: A Feasibility Study.

BACKGROUND The aim of this study was to study the feasibility and acceptability of electroacupuncture (EA) for preventing postoperative gastrointestinal complications in patients undergoing thoracoscopic segmentectomy/lobectomy. MATERIAL AND METHODS Sixty patients who underwent video-assisted thoracoscopic (VATS) segmentectomy/lobectomy received either EA treatments plus usual care (EA group) or usual care alone (UC group). Patients in the EA group were given 30 minutes of bilateral electroacupuncture on 3 acupoints [Neiguan (PC6), Zusanli (ST36), and Shangjuxu (ST37)] at 3 time points (24 hours before surgery, and 4 hours and 24 hours after surgery). The primary outcomes were recruitment, retention, acceptability of the EA intervention, incidence and severity of abdominal distension (AD), and time to first flatus and defecation. Secondary outcomes included postoperative nausea and vomiting (PONV), pain intensity, and duration of hospital stay. RESULTS We recruited 60 participants and 59 were randomized into 2 groups for this study: 30 in the EA group and 29 in the UC group. In total, 57 participants completed the study. With the exception of one participant in the EA group, all participants completed all three sessions of EA. The one exclusion was a case where a paravertebral block was not used during the surgery. Qualitative findings from the acceptability questionnaire indicated that participants viewed the EA treatment as acceptable. After EA treatment, there was a small but statistically significant improvement in participants' acceptance of EA for alleviating postoperative gastrointestinal discomfort (P=0.001). The EA group showed improved outcomes compared to the UC group in terms of time to first flatus (20.8±4.6 versus 24.1±6.2 hours, P=0.026) and defecation (53.9±6.0 versus 57.5±7.2 hours, P=0.046). No significant differences appeared regarding AD, rescue medication, or duration of hospitalization. PONV and pain intensity were similar in both groups at the recorded time periods. CONCLUSIONS EA is feasible and acceptable to patients undergoing VATS surgery. Our preliminary findings of EA promoting postoperative recovery of gastrointestinal function warrants large randomized controlled trials.

Hepcidin as a key iron regulator mediates glucotoxicity-induced pancreatic ß-cell dysfunction.

It has been well established that glucotoxicity induces pancreatic ß-cells dysfunction; however, the precise mechanism remains unclear. Our previous studies demonstrated that high glucose concentrations are associated with decreased hepcidin expression, which inhibits insulin synthesis. In this study, we focused on the role of low hepcidin level-induced increased iron deposition in ß-cells and the relationship between abnormal iron metabolism and ß-cell dysfunction. Decreased hepcidin expression increased iron absorption by upregulating transferrin receptor 1 (TfR1) and divalent metal transporter 1 (DMT1) expression, resulting in iron accumulation within cells. Prussia blue stain and calcein-AM assays revealed greater iron accumulation in the cytoplasm of pancreatic tissue isolated from db/db mice, cultured islets and Min6 cells in response to high glucose stimulation. Increased cytosolic iron deposition was associated with greater Fe2+ influx into the mitochondria, which depolarized the mitochondria membrane potential, inhibited ATP synthesis, generated excessive ROS and induced oxidative stress. The toxic effect of excessive iron on mitochondrial function eventually resulted in impaired insulin secretion. The restricted iron content in db/db mice via reduced iron intake or accelerated iron clearance improved blood glucose levels with decreased fasting blood glucose (FBG), fasting blood insulin (FIns), HbA1c level, as well as improved intraperitoneal glucose tolerance test (IPGTT) results. Thus, our study may reveal the mechanism involved in the role of hepcidin in the glucotoxcity impaired pancreatic ß cell function pathway.

RETRACTED: Anti-angiogenic effect of Interleukin-26 in oxygen-induced retinopathy mice via inhibiting NFATc1-VEGF pathway.

This article has been retracted: please see Elsevier Policy on Article Withdrawal (http://www.elsevier.com/locate/withdrawalpolicy). This article has been retracted at the request of authors. The Journal received an expression of concern from a reader, which noted that: "The problem is that there is no IL-26 gene in the mouse. They claim they bought the KO mouse and the mouse IL-26 protein but given that there is no mouse IL-26 gene, a purchase is not possible and in fact no such reagents are available. Furthermore they do reference and anti-IL-26 antibody but the spec sheet clearly states that it is only reactive with the human protein…., the Enzo Life Sciences online catalog does not have a listing for recombinant IL-26 of any kind." The authors apologize for their mistakes and have asked to retract the article.

COPB2 promotes cell proliferation and tumorigenesis through up-regulating YAP1 expression in lung adenocarcinoma cells.

Lung adenocarcinoma is the most common subtype of non-small cell lung cancer and responsible for more than 500,000 deaths per year worldwide. In this study, we aimed to explore the effects of COPB2 in the progression of lung adenocarcinoma and its underlying mechanism. The mRNA and protein levels of COPB2 in tumor tissues and cell lines were determined by qRT-PCR and western blotting analysis. siRNAs and over-expressed vector targeting COPB2 were used to down-regulate and up-regulate COPB2 expression in lung adenocarcinoma cell lines H1975. Cell apoptosis rate, proliferation and tumorigenesis of H1975 cells were determined by flow cytometry analysis, MTT assay and in vivo xenotransplantation assay, respectively. Western blotting and immunofluorescence assays were performed to evaluate the effects of COPB on the expression and subcellular location of YAP. Results showed COPB2 was significantly up-regulated in lung adenocarcinoma tissues and cell lines, which showed a close correlation with advanced clinical symptoms, such as tumor differentiation, TNM stage and the occurrence of lymph node metastasis and distance metastasis. Besides, the overall survival time of patients with high expression of COPB2 was shorter than that of patients with low COPB2 expression. After knockdown of COPB2, cell apoptosis rate was increased, whereas cell proliferation was decreased. Compared with that in the normal lung cell line H1688 cells, YAP1 expression was obviously increased in H1975, and over-expression of COPB2 translocated YAP1 from cytoplasm to nuclear, whereas knockdown of COPB2 showed the opposite effect. Overexpression of COPB2 enhanced cell proliferation, tumorigenesis and inhibited cell apoptosis. However, these effects were abolished when down-regulated YAP1 expression on the base of COPB2 over-expression. In conclusion, the increased expression of COPB2 was significantly correlated with the progression of lung adenocarcinoma. Up-regulation of COPB2 inhibited cell apoptosis and promoted cell growth and tumorigenesis through up-regulating YAP1 expression in lung adenocarcinoma.

Synthesis and biological evaluation of a novel ß-D-2'-deoxy-2'-α-fluoro-2'-ß-C-(fluoromethyl)uridine phosphoramidate prodrug for the treatment of hepatitis C virus infection.

A novel ß-D-2'-deoxy-2'-α-fluoro-2'-ß-C-(fluoromethyl)uridine phosphoramidate prodrug (1) has been synthesized. This compound exhibits submicromolar-level antiviral activity in vitro against HCV genotypes 1b, 1a, 2a, and S282T replicons (EC50 = 0.18-1.13 µM) with low cytotoxicity (CC50 > 1000 µM). Administered orally, prodrug 1 is well tolerated at doses of up to 4 g/kg in mice, and produces a high level of the corresponding triphosphate in rat liver.

Synthesis and Anti-HCV Activity of a Novel 2',3'-Dideoxy-2'-α-fluoro-2'-ß-C-methyl Guanosine Phosphoramidate Prodrug.

A novel 2',3'-dideoxy-2'-α-fluoro-2'-ß-C-methyl-6-methoxy guanosine (8) and its phosphoramidate prodrug (1) have been designed and synthesized. Their biological activity was evaluated in both cytotoxicity and cell-based HCV replicon assays. Neither compounds exhibited cytotoxicity up to the highest concentration tested (100 µM) in the Huh-7 cell line. The prodrug (1) displayed nanomolar level antiviral activity (EC50 = 0.39-1.1 µM) against the HCV genotype (GT) 1a, 1b, 2a, and 1b S282T replicons.

Single pemetrexed is noninferior to platinum-based pemetrexed doublet as first-line treatment on elderly Chinese patients with advanced nonsquamous nonsmall cell lung cancer.

BACKGROUND: To evaluate the clinical efficacy and toxicity of single pemetrexed treatment compared with platinum-based pemetrexed doublet pemetrexed-based as first-line treatment for advanced nonsquamous nonsmall cell lung cancer (NS-NSCLC) in elderly Chinese patients. METHODS: The study retrospectively reviewed 175 elderly Chinese patients with NS-NSCLC from June 2010 to September 2013: 90 patients received single pemetrexed treatment, 45 received pemetrexed plus oxaliplatin, and 40 received pemetrexed plus carboplatin. Clinical efficacy was assessed using disease control rate (DCR), overall survival (OS), and progression-free survival (PFS). RESULTS: DCR, OS, and PFS did not significantly differ between single pemetrexed treatment (OS: 14.9 months; DCR: 62.2%; PFS: 3.3 months), pemetrexed plus oxaliplatin (OS: 16.5 months; DCR: 71.1%; PFS: 4.5 months), and pemetrexed plus carboplatin (OS: 15.5 months; DCR: 70.0%; PFS: 4.6 months) groups. Pemetrexed treatment caused significantly lower incidences of adverse events, such as hepatotoxicity and peripheral nerve injury. Performance status (PS), TNM stage, and Thymidylate synthase (TS) expression were predictive factors of DCR. Pemetrexed chemotherapy cycles, PS, and TNM stage were independent prognostic factors. CONCLUSIONS: Single pemetrexed was noninferior to platinum-based pemetrexed doublet for clinical efficacy and safety in elderly Chinese patients with advanced NS-NSCLC. Chemotherapy cycles, performance status, and TNM stage were independent prognostic factors.

A case of 18p deletion syndrome after blepharoplasty.

OBJECTIVE: The deletion of the short arm of chromosome 18 is thought to be one of the rare chromosomal aberrations. Here, we report a case to review this disease. CASE REPORT: The proband is a five-and-a-half-year-old girl who has had phenotypes manifested mainly by ptosis, broad face, broad neck with low posterior hairline, mental retardation, short stature, and other malformations. Chromosomal analysis for her mother showed a normal karyotype. Her father and younger brother were phenotypically normal. RESULT: Phenotypical features were quite similar throughout other cases and in accordance with the usual phenotype of del(18p) suggested within the same cases and among the del(18p) cases described. She underwent blepharoplasty, which improved her appearance. CONCLUSION: 18p deletion syndrome is diagnosed by gene analysis. Plastic surgeries for improving the appearance might be an option for these patients.

Synthesis of Quinazolines from N,N'-Disubstituted Amidines via I2/KI-Mediated Oxidative C-C Bond Formation.

An I2/KI-promoted oxidative C-C bond formation reaction from C(sp3)-H and C(sp2)-H bonds has been used to construct quinazoline skeletons from N,N'-disubstituted amidines. The required substrates are readily prepared from the corresponding acyl chlorides, anilines, and alkyl/benzylamines by sequential amidation, chlorination, and amination reactions. Under the optimal oxidative cyclization conditions, all these amidines were conveniently transformed into the expected products in moderate to good yields. This practical and environmentally benign approach works well with crude amidine intermediates and can also be carried out on a gram scale.

Synthesis of Novel Imidazo[1,2-a]pyridin-2-amines from Arylamines and Nitriles via Sequential Addition and I2 /KI-Mediated Oxidative Cyclization.

A novel and practical strategy for the construction of imidazo[1,2-a]pyridin-2-amine frameworks has been developed. The present sequential approach involves addition of arylamines to nitriles and I2 /KI-mediated oxidative C-N bond formation without purification of the intermediate amidines. This operationally simple synthetic process provides a facile access to a variety of new 2-amino substituted imidazo[1,2-a]pyridines and related heterocyclic compounds in an efficient and scalable fashion.

Endoscopical Orbital Fat Decompression with Medial Orbital Wall Decompression for Dysthyroid Optic Neuropathy.

OBJECTIVE: To describe a novel approach to orbital decompression for dysthyroid optic neuropathy (DON). METHODS: An augmented endoscopic transethmoid medial orbital wall decompression (ETMOWD) was performed on 43 consecutive patients (72 eyes) with DON in order to access the orbital apex adequately. Concurrently, endoscopic transethmoid fat decompression (ETFD) using a novel aspiration/cutting instrument to remove orbital fat was performed for further reduction of proptosis. All patients were followed up periodically for at least 6 months. Outcomes such as improvement of visual acuity (VA), color vision, degree of proptosis reduction as well as the incidence of surgical induced diplopia were analyzed at the final review. RESULTS: Sixty-nine out of 72 eyes (95.8%) had a statistically significant improvement in VA from -0.65 ± 0.30 to -0.25 ± 0.22 postoperatively, with a mean improvement of 0.55 ± 0.17 (p < 0.001). Thirty-four out of 45 eyes had an improvement in color vision (p < 0.001). The range of proptosis reduction was 4 to 9 mm (mean 6.2 ± 1.2 mm). Postoperative symmetry was achieved to within 2 mm using an exophthalmometer in 39 of 43 patients (90.7%). Five patients developed diplopia in the postoperative phase, but had complete resolution within 3 months. Two patients had further deterioration in their diplopia following surgery. CONCLUSION: Our technique of a combined ETFD with ETMOWD appears to be effective in managing patients with DON, with minimal morbidities and a low incidence of postoperative diplopia.

I2/KI-Mediated Oxidative N-N Bond Formation for the Synthesis of 1,5-Fused 1,2,4-Triazoles from N-Aryl Amidines.

An I2/KI-mediated oxidative N-N bond formation reaction is described. This new and environmentally benign approach allows for the convenient synthesis of a variety of 1,2,4-triazolo[1,5-a]pyridines and other 1,5-fused 1,2,4-triazoles from readily available N-aryl amidines in an efficient and scalable fashion.

Design, synthesis, and biological evaluation of new N(4)-Substituted 2'-deoxy-2'-fluoro-4'-azido cytidine derivatives as potent anti-HBV agents.

A series of new 2'-deoxy-2'-ß-fluoro-4'-azido-ß-d-arabinofuranosyl cytidine derivatives bearing heteroatom-containing N(4)-substituents were designed and synthesized. Antiviral screening in HepG2.2.15 cells identified three analogs (1a, 1d &1g) with good anti-HBV activity and low cytotoxicty. Of them, compound 1g exhibited significant inhibitory activity on both HBV antigens secretion (EC50, HBsAg = 9 nM, EC50, HBeAg = 0.25 µM) and viral DNA replication (intracellular, EC50 = 0.099 µM; extracellular, EC50 < 0.01 µM).

Concise Synthesis of Taiwaniaquinol B and 5-epi-Taiwaniaquinone G.

The natural product taiwaniaquinol B and the unnatural 5-epi-taiwaniaquinone G were synthesized based on a highly efficient tandem acylation-Nazarov cyclization approach to build the tricyclic skeleton.