Inflammatory Cell-Derived MYDGF Attenuates Endothelial LDL Transcytosis to Protect Against Atherogenesis.

BACKGROUND: Inflammation contributes to the pathogenesis of atherosclerosis. But little is known about the potential benefits of inflammatory cells to atherosclerosis. The aim of this study was to investigate the function of inflammatory cells/endothelium axis and determine whether and how inflammatory cell-derived MYDGF (myeloid-derived growth factor) inhibited endothelial LDL (low-density lipoprotein) transcytosis. METHODS: In in vivo experiments, both loss- and gain-of-function strategies were used to evaluate the effect of inflammatory cell-derived MYDGF on LDL transcytosis. We generated monocyte/macrophage-targeted MYDGF-null mice on an Ldlr (LDL receptor)-/- background in the loss-of-function strategy and restored the inflammatory cell-derived MYDGF by bone marrow transplantation and inflammatory cell-specific overexpression of MYDGF mice model in the gain-of-function strategy. In in vitro experiments, coculture experiments between primary mouse aortic endothelial cells and macrophages and mouse aortic endothelial cells supplemented with or without recombinant MYDGF were conducted. RESULTS: Inflammatory cell-derived MYDGF deficiency aggravated endothelial LDL transcytosis, drove LDL uptake by artery wall, and thus exacerbated atherosclerosis in vivo. Inflammatory cell-derived MYDGF restoration by bone marrow transplantation and inflammatory cell MYDGF overexpression alleviated LDL transport across the endothelium, prevented LDL accumulation in the subendothelial space, and subsequently ameliorated atherosclerosis in vivo. Furthermore, in the in vitro study, macrophages isolated from MYDGF+/+ mice and recombinant MYDGF attenuated LDL transcytosis and uptake in mouse aortic endothelial cells. Mechanistically, MYDGF inhibited MAP4K4 (mitogen-activated protein kinase kinase kinase kinase isoform 4) phosphorylation, enhanced activation of Akt (protein kinase B)-1, and diminished the FoxO (forkhead box O) 3a signaling cascade to exert protective effects of MYDGF on LDL transcytosis and atherosclerosis. CONCLUSIONS: The findings support a role for inflammatory cell-derived MYDGF served as a cross talk factor between inflammatory cells and endothelial cells that inhibits LDL transcytosis across endothelium. MYDGF may become a novel therapeutic drug for atherosclerosis, and the beneficial effects of inflammatory cell in atherosclerosis deserve further attention.

Identification of RPGR ORF15 mutation for X-linked retinitis pigmentosa in a large Chinese family and in vitro correction with prime editor.

X-linked retinitis pigmentosa (XLRP) is the most severe form of Retinitis Pigmentosa (RP) and one of the leading causes of blindness in the world. Currently, there is no effective treatment for RP. In the present study, we recruited a XLRP family and identified a 4 bp deletion mutation (c. 2234_2237del) in RPGR ORF15 with Sanger sequencing, which was located in the exact same region as the missing XES (X chromosome exome sequencing) coverage. Then, we generated cell lines harboring the identified mutation and corrected it via enhanced prime editing system (ePE). Collectively, Sanger sequencing identified a pathogenic mutation in RPGR ORF15 for XLRP which was corrected with ePE. This study provides a valuable insight for genetic counseling of the afflicted family members and prenatal diagnosis, also paves a way for applying prime editing based gene therapy in those patients.

Best-corrected visual acuity results facilitate molecular diagnosis of infantile nystagmus patients harboring FRMD7 mutations.

The visual function of patients with infantile nystagmus (IN) can be significantly decreased owing to constant eye movement. While, reaching a definitive diagnosis becomes a challenge due to genetic heterozygous of this disease. To address it, we investigated whether best-corrected visual acuity (BCVA) results can facilitate the molecular diagnosis of IN patients harboring FRMD7 mutations. 200 patients with IN from 55 families and 133 sporadic cases were enrolled. Mutations were comprehensively screened by direct sequencing using gene-specific primers for FRMD7. We also retrieved related literature to verify the results based on our data. We found that the BCVA of patients with IN harboring FRMD7 mutations was between 0.5 and 0.7, which was confirmed by data retrieved from the literature. Our results showed that BCVA results facilitate the molecular diagnosis of patients with IN harboring FRMD7 mutations. In addition, we identified 31 FRMD7 mutations from the patients, including six novel mutations, namely, frameshift mutation c.1492_1493insT (p.Y498LfsTer14), splice-site mutation c.353C > G, three missense mutations [c.208C > G (p.P70A), c.234G > A (p.M78I), and c.1109G > A (p.H370R)], and nonsense mutation c.1195G > T (p.E399Ter). This study demonstrates that BCVA results may facilitate the molecular diagnosis of IN patients harboring FRMD7 mutations.

Cytokeratin 7 Expression and Mismatch Repair Status for Survival Prediction in Patients With Low Rectal Cancer After Neoadjuvant Therapy.

BACKGROUND: More than half of the patients with locally advanced low rectal cancer exhibit no or minor response to nCRT. It is important to investigate the predictive and prognostic values of potential biomarkers in patients with locally advanced low rectal cancer receiving nCRT. MATERIALS AND METHODS: This retrospective study included 162 patients with locally advanced low rectal cancer who underwent nCRT, followed by total mesorectal excision (TME) between 2016 and 2019. Cytokeratin 7 (CK7) expression and mismatch repair (MMR) status were determined by immunohistochemistry (IHC). Categorical variables were compared using the chi-square test. Overall survival (OS) and disease-free survival (DFS) curves were estimated using the Kaplan-Meier and Cox methods. RESULTS: There were predominance significant differences in distance from anus margin (P < .0001) and circumferential extent of the tumor (P < .0001).CK7 positive expression was detected in 21 of the 162 patients (13%). The univariate and multivariate analysis revealed that patients whose tumors had CK7 positive expression had significantly shorter OS (HR = 3.878, P = .038; HR = 1.677, P = .035) and DFS (HR = 3.055, P = .027;HR = 3.569, P = .038) than those with CK7 negative expression. While patients with CK7 positive expression had a higher proportion of worse TRG compared with CK7 negative patients (P = .001). Patients with deficient mismatch repair (dMMR) just occupied a small proportion (8.6%), but there was still a close connection between the MMR status and recurrence after TME (P = .045). MMR status was an independent risk factor affecting the OS (HR = .307, P < .0001; HR = .123, P < .0001) and DFS (HR = .288, P < .0001; HR = .286, P < .0001) by univariate and multivariate analysis. But no significant difference in the proportion of TRG was observed between patients with dMMR and pMMR (P = .920). CONCLUSIONS: The result confirms negative prognostic role of CK7-positive and dMMR statuses, which have potential predictive value for neoadjuvant chemoradiotherapy response. This provides opportunity to modify individualized treatment strategies for patients with different CK7 expression levels and dMMR statuses.

Neuregulin 4 Attenuates Osteoarthritis Progression by Inhibiting Inflammation and Apoptosis of Chondrocytes in Mice.

Osteoarthritis (OA) is characterized by chondrocyte apoptosis and increased degradation of type II collagen. Inflammation is one of the major risk factors involved in the pathophysiology of OA. Neuregulin 4 (Nrg4) plays a protective role in a variety of low-level inflammatory diseases, such as non-alcoholic fatty liver disease, inflammatory bowel disease, or type 2 diabetes mellitus. Here we found that (1) Nrg4 deficiency aggravated the destruction and inflammation of articular cartilage and the apoptosis of chondrocytes in vivo. (2) Nrg4 restoration reversed these changes in vivo. (3) Murine recombinant Nrg4 (rNrg4) suppressed inflammation and apoptosis of chondrocytes and decreased the degradation of extracellular matrix in vitro. (4) Mechanistically, the mitogen-activated protein kinase/c-jun N-terminal kinase (MAPK/JNK) signaling pathway may be involved in the regulation of Nrg4 in the pathophysiology of OA. Therefore, we concluded that Nrg4 alleviated the progression of OA by inhibiting the inflammation, protecting against apoptosis of chondrocyte, and decreasing the degradation of extracellular matrix in a manner involving MAPK/JNK signaling.

Facet-dependent surface charge and Pb2+ adsorption characteristics of hematite nanoparticles: CD-MUSIC-eSGC modeling.

Accurate prediction of the environmental fate of Pb depends on the understanding of Pb coordination to mineral surfaces. Here, the proton and Pb adsorption and speciation on hematite nanocrystals with different exposed crystallographic facets were investigated. High-resolution transmission electron microscopy images revealed that hematite nanoplates (HNP) were of 75.3 ± 9.5% (001) facets and 24.6 ± 9.3% (012) facets, while hematite nanocubes (HNC) were of 76.0 ± 11.1% (012) facets and 24.0 ± 3.2% (110) facets. Our modeling results revealed that the proton affinity constant (log KH) of ≡FeOH-0.5 and ≡Fe3O-0.5 was 7.8 and 10.8 on hematite (012) facets, and changed to 7.7 and 11.7 on (110) facets, respectively. Owing to the different atomic arrangements, (012) facets not only have higher adsorption performance for Pb, but also present a greater dependence on pH than (110) facets. Additionally, our modeling further indicated that (012) facets bind Pb via both bidentate and tridentate complexes, while (110) facets bind Pb only through bidentate complexes at pH 3.0-6.5. These results facilitate a more detailed understanding of the complex species of Pb on hematite surface while also provide new insight into the reactivity mechanism of individual hematite facets.

GABAA receptor-mediated inhibition of Dahlgren cells electrical activity in the olive flounder, Paralichthys olivaceus.

γ-Aminobutyric acid (GABA) is a major inhibitory neurotransmitter in the central nervous system. We investigated its potential role as a neurotransmitter in the neuroendocrine Dahlgren cell population of the caudal neurosecretory system (CNSS) of the flounder Paralichthys olivaceus. The application of GABA in vitro resulted in a decrease in electrical activity of Dahlgren cells, followed by an increase of the number of silent cells, together with a decreased firing frequency of all three activity patterns (tonic, phasic, bursting). GABAA receptor agonist etomidate decreased Dahlgren cell firing activity, in a similar way to GABA. The response to GABA was blocked by the GABAA receptor antagonist bicuculline. GABAA receptor gamma2 subunit (Gabrg2) and chloride channel (Clcn2) mRNA expression were significantly upregulated in the CNSS after GABA superfusion. These data suggest that GABA may modulate CNSS activity in vivo mediated by GABAA receptors.

Phosphate Ion-Functionalized CoS with Hexagonal Bipyramid Structures from a Metal-Organic Framework: Bifunctionality towards Supercapacitors and Oxygen Evolution Reaction.

To solve energy-related environmental problems and the energy crisis, efficient electrochemical materials have been developed as alternative energy storage and conversion systems. Abundant transition metals and their sulfides are attractive electrochemical materials. Herein, we report an efficient phosphorization strategy, which improves the overall electrochemical performance of metal sulfides. In detail, CoS hexagonal bipyramids were synthesized through simple calcination combined with in situ sulfurization of a cobalt-based metal-organic framework template, and then phosphate ion-functionalized CoS (P-CoS) was prepared through a phosphorization reaction. P-CoS exhibited outstanding electrochemical activity as both supercapacitor electrode and oxygen evolution reaction (OER) catalyst. Supercapacitors based on CoS and P-CoS as the electrodes had high specific capacitances of 304 and 442 F g-1 , respectively, and remained stable for over 10 000 cycles at 5 A g-1 . For OER, P-CoS showed a current density of 10 mA cm-2 at an overpotential of 340 mV, with a small Tafel slope. In conclusion, functionalizing CoS with phosphate ions is a promising method for enhancing chemical reactivity and accelerating ion and electron transfer.

Factors influencing the self-reported sense of deviation in adults with successful surgical outcomes for strabismus.

BACKGROUND: To determine whether a sense of deviation remains in adults with successful motor alignment who fulfil diplopia criteria after surgery and to examine the factors associated with this judgement. METHODS: This was a retrospective study. Adult patients defined as having a successful outcome based on more than 1 year of post-operative follow-up visits were included in the study. The sense of deviation was determined at the last visit. Pre- and post-operative deviation and characteristics including age, gender, education level, occupation, diagnosis, size of deviation, extraocular movement (EOM), binocular function, and health-related quality of life (HRQOL) were recorded. RESULTS: In total, 22 (24%) of the 91 adults with successful surgical outcomes reported a sense of deviation. No significant differences were noted between subjects with and without a sense of deviation regarding patient demographics, pre- and post-operative deviation, changes in deviation, sensory fusion or EOM. Subjects with a sense of deviation had an increased prevalence of and larger post-operative vertical deviation, poorer stereo function, and lower HRQOL scores than those with no sense of deviation. The presence of post-operative vertical deviation was associated with a sense of deviation. CONCLUSIONS: Approximately one-fourth (24%) of adults defined as having successful surgical outcomes who still had a sense of deviation exhibited worse stereo function, higher vertical deviation size and lower HRQOL scores. The presence of 3 to 5 prism dioptres(pd) of vertical deviation would be the main factor associated with a sense of deviation post-operatively.

Idiopathic cocoon abdomen with congenital colon malrotation: a case report and review of the literature.

BACKGROUND: Cocoon abdomen is a relatively rare abdominal disease characterized by the total or partial encasement of the small intestinal by a dense fibro-collagenous membrane. CASE PRESENTATION: We reported an unusual case of idiopathic cocoon abdomen with congenital colon malrotation. Laparotomy and sac release were performed on the patient. The patient was no recurrence 6 months after operation. A literature review was also performed. CONCLUSION: Preoperative diagnosis of abdominal cocoon is difficult. A careful history, physical examination and appropriate radiology may be helpful in making a definitive diagnosis. If conservative treatment can't relieve symptoms effectively, surgery is currently considered to be important in the management of this disease.

Structure-Designed Synthesis of CoP Microcubes from Metal-Organic Frameworks with Enhanced Supercapacitor Properties.

Metal-organic framework-based supercapacitors have been widely recognized as the best energy storage devices for future portable electronic equipment. Herein, CoP- T ( T = 300, 350, and 400 °C) microcubes with a solid and hollow microstructure were successfully synthesized by low-temperature phosphorization of [CH3NH3][Co(HCOO)3] precursor at desired temperatures. The morphology, structure, and composition of the prepared CoP-350 °C samples were analyzed by scanning electron microscopy, transmission electron microscopy, and X-ray photoelectron spectroscopy. Hollow CoP-350 °C microcube has a larger specific surface area (25.9 m2 g-1) than that of solid ones (16.1 m2 g-1). When the two samples were used as electrode raw materials for supercapacitors, the hollow CoP-350 °C electrode exhibits better electrochemical performance (560 F g-1) than that of the solid one (427.6 F g-1) at a current density of 1 A g-1. The enhanced supercapacitor properties may be attributed to the large surface area and the unique hollow structure. Further, an asymmetric supercapacitor was prepared by employing the hollow CoP-350 °C microcubes as anode and N-doped graphene as cathode. It has a high rate capability (capacitance retention of 69% from 0.5 to 8 A g-1), a high energy density (21.4 W h kg-1 at a power density of 373 W kg-1), and outstanding cycling stability (remained 81.2% after 6000 cycles).

Proton and Copper Binding to Humic Acids Analyzed by XAFS Spectroscopy and Isothermal Titration Calorimetry.

Proton and copper (Cu) binding to soil and lignite-based humic acid (HA) was investigated by combining X-ray absorption fine structure (XAFS) spectroscopy, isothermal titration calorimetry (ITC), and nonideal-competitive-adsorption (NICA) modeling. NICA model calculations and XAFS results showed that bidentate and monodentate complexation occurred for Cu binding to HA. The site-type-specific thermodynamic parameters obtained by combining ITC measurements and NICA calculations revealed that copper binding to deprotonated carboxylic-type sites was entropically driven and that to deprotonated phenolic-type sites was driven by entropy and enthalpy. Copper binding to HA largely depended on the site-type and coordination environment, but the thermodynamic binding mechanisms for Cu binding to the specific site-types were similar for the different HAs studied. By comparing the site-type-specific thermodynamic parameters of HA-Cu complexation with those of low molar mass organic acids, the Cu coordination could be further specified. Bidentate carboxylic-Cu complexes made the dominating contributions to Cu binding to HA. The present study not only yields molecular-scale mechanisms of ion binding to carboxylic- and phenolic-type sites of HA but also provides the new insight that the universal nature of site-type-specific thermodynamic data enables quantitative estimation of the binding structures of heavy metal ions to humic substances.

Modulatory effect of glutamate GluR2 receptor on the caudal neurosecretory Dahlgren cells of the olive flounder, Paralichthys olivaceus.

A neuromodulatory role for glutamate has been reported for magnocellular neuroendocrine cells in mammalian hypothalamus. We examined the potential role of glutamate as a local intercellular messenger in the neuroendocrine Dahlgren cell population of the caudal neurosecretory system (CNSS) in the euryhaline flounder Paralichthys olivaceus. In pharmacological experiments in vitro, glutamate (Glu) caused an increase in electrical activity of Dahlgren cells, recruitment of previously silent cells, together with a greater proportion of cells showing phasic (irregular) activity. The glutamate substrate, glutamine (Gln), led to increased firing frequency, cell recruitment and enhanced bursting activity. The glutamate effect was not blocked by the N-methyl-D-aspartate (NMDA) receptor antagonist MK-801, or the GluR1/GluR3 (AMPA) receptor antagonist IEm1795-2HBr, but was blocked by the broad-spectrum α-amino-3-hydroxy- 5- methyl-4-isoxazo-lepropionic acid (AMPA) receptor antagonist ZK200775. Our transcriptome sequencing study revealed three AMPA receptor (GluR1, GluR2 and GluR3) in the olive flounder CNSS. Quantitative RT-PCR revealed that GluR2 receptor mRNA expression was significant increased following dose-dependent superfusion with glutamate in the CNSS. GluR1 and GluR3 receptor mRNA expression were decreased following superfusion with glutamate. L-type Ca2+ channel mRNA expression had a significant dose-dependent decrease following superfusion with glutamate, compared to the control. In the salinity challenge experiment, acute transfer from SW to FW, GluR2 receptor mRNA expression was significantly higher than the control at 2 h. These findings suggest that GluR2 is one of the mechanisms which can medicate glutamate action within the CNSS, enhancing electrical activity and hence secretory output.

Modulatory effect of dopamine receptor 5 on the neurosecretory Dahlgren cells of the olive flounder, Paralichthys olivaceus.

A neuromodulatory role for dopamine has been reported for magnocellular neuroendocrine cells in the mammalian hypothalamus. We examined its potential role as a local intercellular messenger in the neuroendocrine Dahlgren cell population of the caudal neurosecretory system (CNSS) of the euryhaline flounder Paralichthys olivaceus. In vitro application of dopamine (DA) caused an increase in electrical activity (firing frequency, recorded extracellularly) of Dahlgren cells, recruitment of previously silent cells, together with a greater proportion of cells showing phasic (irregular) activity. The dopamine precursor, levodopa (L-DOPA), also increased firing frequency, cell recruitment and enhanced bursting and tonic activity. The effect of dopamine was blocked by the D1, D5 receptor antagonist SCH23390, but not by the D2, D3, D4 receptor antagonist amisulpride. Transcriptome sequencing revealed that all DA receptors (D1, D2, D3, D4, and D5) were present in the flounder CNSS. However, quantitative RT-PCR revealed that D5 receptor mRNA expression was significantly increased in the CNSS following dopamine superfusion. These findings suggest that dopamine may modulate CNSS activity in vivo, and therefore neurosecretory output, through D5 receptors.

[Screening of nucleic acid aptamer of lung cancer cells based on cell exponential enrichment ligand system evolution and its application in tumor diagnosis and treatment].

Nucleic acid aptamer is an oligonucleotide sequence screened by the exponential enrichment ligand system evolution technology (SELEX). Previous studies have shown that nucleic acid aptamer has a good application prospect in tumor diagnosis and treatment. Therefore, we reviewed the selection and identification of nucleic acid aptamer of lung cancer cells in recent years, and discussed the effect of aptamer as targeting drugs and targeting vectors on the diagnosis of tumors, which provide a new idea for early diagnosis and treatment of tumor.

The Correlation Between Circulating Betatrophin and Insulin Resistance in General Population: A Meta-Analysis.

Many inconsistent findings are reported on the correlation between circulating betatrophin and insulin resistance in the different population. The aim of this analysis was to explore the correlation between the level of betatrophin and insulin resistance in the general population. The databases of PubMed, EMBASE, and the Cochrane Library (inception to October 26, 2016) were searched without language restrictions for publications that reported studies on associations between betatrophin and insulin resistance in adults. Subgroup analyses were performed to investigate potential sources of heterogeneity. The pooled effect size was calculated using a random-effects model. Twenty-five studies were included in this meta-analysis. Meta-analysis showed that betatrophin was positively and significantly correlated with insulin resistance (r=0.16, 95% CI: 0.08-0.25). When all participants were divided into DM, GDM, and Non-DM groups, this association was also significant in T2DM, GDM, and Non-DM participants (T2DM: r=0.09, 95% CI: 0.01-0.17; I 2=45.1%; GDM: r=0.39, 95% CI: 0.24-0.55; I 2=0.0%; non-DM: r=0.15, 95% CI: 0.04-0.26; I 2=89.3%), and it was obvious that heterogeneity existed in Non-DM group (I 2=89.3%, p<0.001). Subgroup analysis revealed that gender, serum sample and ELISA kits for full-length betatrophin had significant influence on the association between betatrophin and insulin resistance. In conclusion, the level of circulating betatrophin is positively associated with insulin resistance in the general population, especially in T2DM and GDM patients. Gender, serum sample, and ELISA kits for full-length betatrophin may affect this association. More large-scale studies are needed to determine whether improving insulin resistance concomitantly declines betatrophin levels in different diseases.

Multilocus sequence typing and clonal population genetic structure of Cyclospora cayetanensis in humans.

To investigate the prevalence of Cyclospora cayetanensis in a longitudinal study and to conduct a population genetic analysis, fecal specimens from 6579 patients were collected during the cyclosporiasis - prevalent seasons in two urban areas of central China in 2011-2015. The overall incidence of C. cayetanensis infection was 1·2% (76/6579): 1·6% (50/3173) in Zhengzhou and 0·8% (26/3406) in Kaifeng (P 0·05). All the isolates clustered in the C. cayetanensis clade based on the small subunit ribosomal RNA gene sequence phylogenetic analysis. There were 45 specimens positive for all the five C. cayetanensis microsatellite loci, and formed 29 multilocus genotypes (MLGs). The phylogenetic relationships of 54 distinct MLGs (including 25 known reference MLGs), based on the concatenated multilocus sequences, formed three main clusters. A population structure analysis showed that the 79 isolates (including 34 known reference isolates) of C. cayetanensis produced three distinct subpopulations based on allelic profile data. In conclusion, we determined the frequency of C. cayetanensis infection in humans in Henan Province. The clonal population structure of the human C. cayetanensis isolates showed linkage disequilibrium and three distinct subpopulations.

Molecular characterisation and expression of parathyroid hormone-related protein in the caudal neurosecretory system of the euryhaline flounder, Platichthys flesus.

Parathyroid hormone-related protein (PTHrP) is a hypercalcemic factor in fish, but the source of circulating PTHrP remains unclear. In this study investigation of the caudal neurosecretory system (CNSS), considered one of major sources of PTHrP in fish, provided valuable insights into this regulatory system. We report pthrpa and pthrpb gene cloning, characterization, expression, and responses to low salinity and hypocalcemia challenge in flounder. The pthrpa and pthrpb precursors, isolated from a European flounder CNSS library, consist of 166 and 192 amino acid residues, respectively, with an overall homology of approximately 59.2%. Both precursors contain a signal peptide and a mature peptide with cleavage and amidation sites. The flounder PTHrPA and PTHrPB peptides share only 41% sequence identity with human PTHrPA. Quantitative PCR analysis demonstrated that the bone and bladder, are respectively major sites of pthrpa and pthrpb expression in flounder. Urophysectomy confirmed the CNSS as a likely contributor to circulating PTHrP peptides. There were no significant differences in CNSS pthrpa and pthrpb mRNA expression or plasma PTHrP levels between seawater (SW) and freshwater (FW)-adapted fish, though plasma total calcium concentrations were higher in FW animals. The intraperitonial administration of EGTA rapidly induced hypocalcemia and concomitant elevation in plasma PTHrP accompanied by increases in both pthrpa and pthrpb expression in the CNSS. Together, these findings support an evolutionary conserved role for PTHrP in the endocrine regulation of calcium.

Comparison of Near Addition Value Prescription Methods for Myopic Children.

PURPOSE: To compare personalized near addition values for myopic children that induce a reasonable phoria (Ph) (meeting Sheard's criterion) and induce a null lag of accommodation at near and to evaluate changes in these metrics after lens adaptation. METHODS: Fifty-three myopic children participated in this study. Accommodative response, Ph, and fusional amplitudes (FAs) were measured at 33 cm through multiple addition lenses (0D, +1.00D, +1.50D, +2.00D, +2.50D, +3.00D). The adaptation effect on measured parameters was evaluated after 6 min of near work with each addition. The FA/Ph ratios were calculated for each addition and fitted using a rational function to obtain the optimal addition value satisfying Sheard's criterion (FA/Ph ≥ 2). Lag of accommodation change in association with addition value was assessed using linear regressions to obtain the addition values inducing a null lag. RESULTS: Lag of accommodation (r = -0.987, p < 0.001) and Ph (r = -0.999, p < 0.001) decreased linearly with addition value. The 6-min adaptation induced a small but significant increase in accommodative lag and an exophoric shift (p < 0.05). Three FA/Ph patterns with respect to addition lenses were observed based on the near Ph: orthophoria/exophoria, low esophoria, and large esophoria. Addition values based on Sheard's criterion (mean ± SD, +2.16 ± 0.79D) were significantly lower than those based on null lag (+2.83 ± 0.44D, t = 19.86, p < 0.001). The FA/Ph ratio was less than 2.0 in 75.5% of subjects with additions determined through null accommodative lag. Additions determined through FA/Ph ≥ 2 induced a lag of accommodation of 0.38 ± 0.42D. CONCLUSIONS: Personalized near addition values using Sheard's criterion were lower than those obtained through null lag of accommodation. These values should allow a better binocular balance especially for exophoric children.

[Regulatory effect of liraglutide on the expression of eNOS in the corpus cavernosum of diabetic rats].

UNLABELLED: OCTOBER: To explore the effects of the glucagon-like peptide 1 (GLP-1) liraglutide on the penile erectile function of rats with diabetic erectile dysfunction (DED) by observing the impact of liraglutide on the expression of eNOS in the corpus cavernosum of diabetic rats. METHODS: We randomly divided 30 six-week-old male SD rats into a normal control (n = 10) and an experimental group (n = 20) , established models of diabetes mellitus (DM) in the experimental rats, and subdivided them into a DM (n = 8) and a GLP-1 group (n = 8) to receive intramuscular injection of normal saline and liraglutide at 5 mg per kg of the body weight per day, respectively. After 12 weeks of intervention, we obtained the levels of FPG, FINS, TG, TC, HDL-C, LDL-C, testosterone, and IL-6 and the indexes of Homa-IR and Homa-ß, detected the expressions of Akt/p-Akt and eNOS/p-eNOS in the corpus cavernosum by Western blot, and compared the erectile function between different groups. RESULTS: The frequency and rate of penile erection were significantly lower in the DM group than in the GLP-1 and normal control groups (P < 0.05) and also lower in the GLP-1 group than in the normal controls (P < 0.05). Immunofluorescence staining showed the expression of eNOS mainly in the cytoplasm of the cavernosal vessels and sinusoidal endothelial cells, markedly lower in the DM and GLP-1 groups than in the normal rats (P < 0.05), but higher in the GLP-1 than in the DM group (P < 0.05). The level of eNOS/p-eNOS in the penile tissue was significantly decreased in the DM and GLP-1 groups in comparison with the normal controls (P < 0.01 or P < 0.05), while that of p-eNOS was markedly increased in the GLP-1 group as compared with the DM group (P < 0.05). No statistically significant differences were observed in the Akt level among the three groups of animals (P > 0.05). The expression of p-Akt was remarkably reduced in the DM and GLP-1 groups in comparison with the control rats (P < 0.01 or P < 0.05), but higher in the GLP-1 than in the DM group (P < 0.05). CONCLUSION: GLP-1 can protect the function of endothelial cells in the corpus cavernosum and improve the erectile function of DED rats by regulating the Akt/ eNOS signaling pathway, which indicates that GLP-1 could be an important option for the treatment and prevention of DED.