Identification of Mudanjiang Phlebovirus in the Daxing'anling Region of China.

Mudanjiang phlebovirus (MJPV) is a newly discovered phlebovirus, initially detected from Ixodes persulcatus ticks in China in 2022. In this study, by next-generation sequencing (NGS) on a wide variety of ticks and wild small animals in China, we detected MJPV from I. persulcatus and Meriones meridianus. Additionally, we conducted RT-PCR and sequencing on 1815 adult ticks and 805 wild small mammals collected from eight provinces in China between 2017 and 2021. MJPV RNA-positive results were found in 0.22% (4/1815) of tick samples, as well as in 0.12% (1/805) of rodent samples. All positive detections were obtained from Heilongjiang and Inner Mongolia. Sequencing analysis revealed nucleotide similarities ranging from 98.23% to 99.11%, as well as amino acid similarities ranging from 99.12% to100%, between the current MJPV strain and previously reported strains of MJPV. Phylogenetic tree analysis demonstrated that the previously reported MJPV strain along with our two variants clustered together with other tick-borne phenuiviruses, indicating their close relationship within this viral group. This study represents the first detection of MJPV infection in wild rodents, expanding the known host range for this virus in the endemic regions.

Reduced nitrogen fertilization from pre-flowering to pre-veraison alters phenolic profiles of Vitis vinifera L. Cv. Cabernet Gernischt wine of Yantai, China.

Nitrogen (N) fertilization is important for grape growth and wine quality. Unreasonable N fertilizer application affects wine growth and has a negative impact on wine quality. Therefore, it is essential to address the mismatch between N application and wine composition. To regulate vine growth and improve grape and wine quality, Cabernet Gernischt (Vitis vinifera L.) grapevines were subjected to lower levels of N, compared to normal N supply treatments, during the grape growing seasons of 2019 and 2020 in the wine region of Yantai, China. The effects of reduced N application from pre-boom to pre-veraison on vine growth, yield and composition of grapes, and dry red wine anthocyanin and non-anthocyanin phenolic compound content were studied. We found that reduced N application significantly decreased dormant shoot fresh mass and yield. However, the effect of N application on fruit ripening depended on the season. Nitrogen-reduction treatment significantly improved wine phenolic parameters, including total phenolics, tannins, and anthocyanins, and enhanced most of the individual anthocyanins and some non-anthocyanin phenolics, especially stilbenes, including piceatannol, trans-resveratrol, and polydatin, regardless of the season. Overall, our findings highlight the importance of reducing N application during the grape growing season in order to modify the wine phenolic profiles.

Modification of wine phenolic profiles by gibberellic acid application in 'Cabernet Gernischt' grapevines before anthesis.

BACKGROUND: Vitis vinifera L. 'Cabernet Gernischt' grapes from the Yantai wine region of China usually form dense clusters and contain low phenolic content. We applied five concentrations (ranged from 5 to 25 mg L-1 ) of gibberellic acid (GA3 ) to 'Cabernet Gernischt' before anthesis to decrease cluster compactness in two consecutive vintages. Yield indices, grape maturity, and wine phenolic compounds were determined. RESULTS: GA3 application significantly reduced cluster compactness, bunch weight, and yield per vine, but it did not significantly improve fruit ripening. The levels of total phenolics, total tannins, and total anthocyanins in wine were enhanced by GA3 application, with 10 and 15 mg L-1 GA3 treatments consistently producing a significant increase in the concentrations of mavidin, cyanidin, and their derivatives. Specifically, trans-resveratrol was consistently significantly increased by 15 mg L-1 GA3 application. Principal component analysis of phenolic compounds demonstrated the differences among wines produced from GA3 treatment groups and the control. CONCLUSION: Overall, wine phenolic profiles could be significantly modified by application of low concentrations of GA3 before anthesis. Application of high levels of GA3 is not recommended due to significant yield decrease. © 2022 Society of Chemical Industry.

Co-winemaking with Vitis amurensis Rupr. "Beibinghong" enhances the quality of Vitis vinifera L. cv. Cabernet Gernischt wine.

In some wine regions of China, Cabernet Gernischt (CG; Vitis vinifera L.) grape berries usually exhibit low pigment content and titratable acidity, and low sensory quality of the resulting wine. The aim of this study was to evaluate co-winemaking of CG wines using the red grape cultivar Beibinghong (BBH; Vitis amurensis Rupr.) at different proportions in terms of alcohols, phenolic compounds, and sensory properties of the wines. The results showed that the co-winemaking wines contained a similar content of higher alcohols, whereas the methanol content increased with an increase in BBH proportion, although this was still corresponded with the national standard. Significantly higher levels of titratable acidity were observed in co-winemaking wines at the ratio of 6:4 and 5:5, compared with monocultivar CG wines. All co-winemaking wines, except CG:BBH (9:1) wine, showed significantly higher levels of total anthocyanins, total phenolics, total tannins, and total flavan-3-ols. Further, individual phenolics, primarily diglucoside anthocyanins and non-anthocyanins (trans-ferulic acid, myricetin, viniferin, trans-caffeic acid, 3,4-dihydroxybenzoic acid), as important contributors to wine color intensity, permitted the differentiation of the wines via principal component analysis. In most cases, co-winemaking wines exhibited higher scores of the 10 sensory attributes on color, aroma, mouthfeel, and overall quality compared with monocultivar wines. Co-winemaking CG wines with BBH at 7:3 ratio demonstrated the highest scores of color intensity, aroma intensity, aroma quality, and overall quality. The results indicate that co-winemaking with V. amurensis grape variety may be useful to enhance V. vinifera wine quality by modifying wine composition. PRACTICAL APPLICATION: Cabernet Gernischt (CG) is the predominant grape cultivar used to prepare premium-quality wine in China; however, in some wine regions, CG wines have low levels of pigment and titratable acidity, and low sensory quality. Co-winemaking with another native grape cultivar, Beibinghong (BBH), which is characterized by a higher content of anthocyanins and acidity, provided sufficient experimental evidence of adjustments in the Vitis vinifera wine composition leading to improved wine sensory quality.

EppR, a new LysR-family transcription regulator, positively influences phenazine biosynthesis in the plant growth-promoting rhizobacterium Pseudomonas chlororaphis G05.

Pseudomonas chlororaphis G05 has the capability to repress the mycelial growth of many phytopathogenic fungi by producing and secreting certain antifungal compounds, including phenazines and pyrrolnitrin. Although some regulatory genes have been identified to be involved in antifungal metabolite production, the regulatory mechanism and pathway of phenazine-1-carboxylic acid biosynthesis remain poorly defined. To identify more new regulatory genes, we applied transposon mutagenesis with the chromosomal lacZ fusion strain G05Δphz::lacZ as an acceptor. In the white conjugant colony G05W05, a novel transcriptional regulator gene, eppR, was verified to be interrupted by the transposon mini-Tn5Kan. To evaluate the specific function of eppR, we created a set of eppR-deletion mutants, including G05ΔeppR, G05Δphz::lacZΔeppR and G05Δprn::lacZΔeppR. By quantifying the production of antifungal compounds and ß-galactosidase expression, we found that the expression of the phenazine biosynthetic gene cluster (phz) and the production of phenazine-1-carboxylic acid were markedly reduced in the absence of EppR. Moreover, the pathogen suppression test verified that the yield of phenazine-1-carboxylic acid was significantly decreased when eppR was deleted in frame. At the same time, no changes in the expression of the phzI/phzR quorum-sensing (QS) system and the production of N-acyl homoserine lactones (AHLs) and pyrrolnitrin were found in the EppR-deficient mutant. In addition, chromosomal fusion analyses and quantitative real-time polymerase chain reaction (qRT-PCR) results also showed that EppR could positively mediate the expression of the phz cluster at the posttranscriptional level. In summary, EppR is specifically essential for phenazine biosynthesis but not for pyrrolnitrin biosynthesis in P. chlororaphis.

LysR-type transcriptional regulator FinR is required for phenazine and pyrrolnitrin biosynthesis in biocontrol Pseudomonas chlororaphis strain G05.

Phenazine-1-carboxylic acid and pyrrolnitrin, the two secondary metabolites produced by Pseudomonas chlororaphis G05, serve as biocontrol agents that mainly contribute to the growth repression of several fungal phytopathogens. Although some regulators of phenazine-1-carboxylic acid biosynthesis have been identified, the regulatory pathway involving phenazine-1-carboxylic acid synthesis is not fully understood. We isolated a white conjugant G05W03 on X-Gal-containing LB agar during our screening of novel regulator candidates using transposon mutagenesis with a fusion mutant G05Δphz::lacZ as a recipient. By cloning of DNA adjacent to the site of the transposon insertion, we revealed that a LysR-type transcriptional regulator (LTTR) gene, finR, was disrupted in the conjugant G05W03. To confirm the regulatory function of FinR, we constructed the finR-knockout mutant G05ΔfinR, G05Δphz::lacZΔfinR, and G05Δprn::lacZΔfinR, using the wild-type strain G05 and its fusion mutant derivatives as recipient strains, respectively. We found that the expressions of phz and prn operons were dramatically reduced in the finR-deleted mutant. With quantification of the production of antifungal metabolites biosynthesized by the finR-negative strain G05ΔfinR, it was shown that FinR deficiency also led to decreased yield of phenazine-1-carboxylic acid and pyrrolnitrin. In addition, the pathogen inhibition assay confirmed that the production of phenazine-1-carboxylic acid was severely reduced in the absence of FinR. Transcriptional fusions and qRT-PCR verified that FinR could positively govern the transcription of the phz and prn operons. Taken together, FinR is required for antifungal metabolite biosynthesis and crop protection against some fungal pathogens.Key points• A novel regulator FinR was identified by transposon mutagenesis.• FinR regulates antifungal metabolite production.• FinR regulates the phz and prn expression by binding to their promoter regions.

A Chimeric Cationic Peptide Composed of Human ß-Defensin 3 and Human ß-Defensin 4 Exhibits Improved Antibacterial Activity and Salt Resistance.

Human beta-defensins (hBDs) play an important role in the host defense against various microbes, showing different levels of antibacterial activity and salt resistance in vitro. It is of interest to investigate whether can chimeric hBD analogs enhanced antibacterial activity and salt resistance. In this study, we designed a chimeric human defensin, named H4, by combining sequences of human beta-defensin-3 (hBD-3) and human beta-defensin-4 (hBD-4), then evaluated its antibacterial activity, salt resistance, and cytotoxic effects. The result showed that the antibacterial activity of H4 against most tested strains, including Klebsiella pneumonia, Enterococcus faecalis, Staphyloccocus aureus, Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumonia, and Acinetobacter baumannii was significantly improved compared to that of hBD-3 and hBD-4. Notably, H4 exhibited significantly better antibacterial activity against multidrug resistant isolate A. baumannii MDR-ZJ06 than commonly used antibiotics. Chimeric H4 still showed more than 80% antibacterial activity at high salt concentration (150 µM), which proves its good salt tolerance. The cytotoxic effect assay showed that the toxicity of H4 to Hela, Vero, A549 cells and erythrocytes at a low dose (<10 µg/ml) was similar to that of hBD-3 and hBD-4. In conclusion, given its broad spectrum of antibacterial activity and high salt resistance, chimeric H4 could serve as a promising template for new therapeutic antimicrobial agents.

Motion Imagery-BCI Based on EEG and Eye Movement Data Fusion.

Existing studies have demonstrated that eye tracking can be a complementary approach to Electroencephalogram (EEG) based brain-computer interaction (BCI), especially in improving BCI performance in visual perception and cognition. In this paper, we proposed a method to fuse EEG and eye movement data extracted from motor imagery (MI) tasks. The results of the tests showed that on the feature layer, the average MI classification accuracy from the fusion of EEG and eye movement data was higher than that of pure EEG data or pure eye movement data, respectively. Besides, we also found that the average classification accuracy from the fusion on the decision layer was higher than that from the feature layer. Additionally, when EEG data were not available for the shifting of parts of electrodes, we combined EEG data collected from the rest of the electrodes (only 50% of the original) with the eye movement data, and the average MI classification accuracy was only 1.07% lower than that from all available electrodes. This result indicated that eye movement data was feasible to compensate for the loss of the EEG data in the MI scenario. Overall our approach was proved valuable and useful for augmenting MI based BCI applications.

Pip serves as an intermediate in RpoS-modulated phz2 expression and pyocyanin production in Pseudomonas aeruginosa.

Pyocyanin, a main virulence factor that is produced by Pseudomonas aeruginosa, plays an important role in pathogen-host interaction during infection. Two copies of phenazine-biosynthetic operons on genome, phz1 (phzA1B1C1D1E1F1G1) and phz2 (phzA2B2C2D2E2F2G2), contribute to phenazine biosynthesis. In our previous study, we found that RpoS positively regulates expression of the phz2 operon and pyocyanin biosynthesis in P. aeruginosa PAO1. In this work, when a TetR-family regulator gene, pip, was knocked out, we found that pyocyanin production was dramatically reduced, indicating that Pip positively regulates pyocyanin biosynthesis. With further phenazines quantification and ß-galactosidase assay, we confirmed that Pip positively regulates phz2 expression, but does not regulate phz1 expression. In addition, while the rpoS gene was deleted, expression of pip was down-regulated. Expression of rpoS in the wild-type PAO1 strain, however, was similar to that in the Pip-deficient mutant PAΔpip, suggesting that expression of pip could positively be regulated by RpoS, whereas rpoS could not be regulated by Pip. Taken together, we drew a conclusion that Pip might serve as an intermediate in RpoS-modulated expression of the phz2 operon and pyocyanin biosynthesis in P. aeruginosa.

phz1 contributes much more to phenazine-1-carboxylic acid biosynthesis than phz2 in Pseudomonas aeruginosa rpoS mutant.

Pseudomonas aeruginosa PAO1, a common opportunistic bacterial pathogen, contains two phenazine-biosynthetic operons, phz1 (phzA1 B1 C1 D1 E1 F1 G1 ) and phz2 (phzA2 B2 C2 D2 E2 F2 G2 ). Each of two operons can independently encode a set of enzymes involving in the biosynthesis of phenazine-1-carboxylic acid. As a global transcriptional regulator, RpoS mediates a lot of genes involving secondary metabolites biosynthesis in many bacteria. In an other previous study, it was reported that RpoS deficiency caused overproduction of pyocyanin, a derivative of phenazine-1-carboxylic acid in P. aeruginosa PAO1. But it is not known how RpoS mediates the expression of each of two phz operons and modulates phenazine-1-carboxylic acid biosynthesis in detail. In this study, by deleting the rpoS gene in the mutant PNΔphz1 and the mutant PNΔphz2, we found that the phz1 operon contributes much more to phenazine-1-carboxylic acid biosynthesis than the phz2 operon in the absence of RpoS. With the construction of the translational and transcriptional fusion vectors with the truncated lacZ reporter gene, we demonstrated that RpoS negatively regulates the expression of phz1 and positively controls the expression of phz2, and the regulation of phenazine-1-carboxylic acid biosynthesis mediated by RopS occurs at the posttranscriptional level, not at the transcriptional level. Obviously, two copies of phz operons and their differential expression mediated by RpoS might help P. aeruginosa adapt to its diverse environments and establish infection in its hosts.

[Isolation, identification and fermentation optimization of Bacillus tequilensis PanD37 producing L-aspartate α- decarboxylase].

OBJECTIVE: We screened bacteria producing L-aspartate α-decarboxylase from grapery soil and optimized the fermentation conditions. METHODS: L-aspartate α-decarboxylase producing bacteria were screened by color-changing circle and liquid secondary screening culture media. Combination of morphological, physiological and biochemical characteristics and 16S rRNA sequence analysis were used to identify the bacteria. Fermentation conditions were optimized by single factor test and orthogonal experiment. RESULTS: Strain PanD37 showed high L-aspartate α-decarboxylase producing property and was identified as Bacillus tequilensis. The optimum fermentation conditions of PanD37 were liquid volume of 50 mL in 500 mL flask, 220 r/min at 35 °C, inoculation amount of 5% for 28 h with a medium of 22.5 g/L sucrose, 7.5 g/L fumaric acid, 20 g/L peptone, 6 g/L L-aspartic acid, 2 g/L Triton X-100, at initial pH of 7.0. Under the optimal fermentation conditions, the highest L-aspartate α-decarboxylase activity reached 44.57 U/mL, which was 2.57 folds higher than that obtained before optimization. CONCLUSION: Strain PanD37 was identified as Bacillus tequilensiswhich was capable of highly producing L-aspartate α-decarboxylase under the optimal fermentation conditions.

Anti-vascular endothelial growth factor for control of wound healing in glaucoma surgery.

BACKGROUND: Trabeculectomy is performed as a treatment for glaucoma to lower intraocular pressure (IOP). The surgical procedure involves creating a channel through the wall of the eye. However scarring during wound healing can block this channel which will lead to the operation failing. Anti-vascular endothelial growth factor (VEGF) agents have been proposed to slow down healing response and scar formation. OBJECTIVES: To assess the effectiveness of anti-VEGF therapies administered by subconjunctival injection for the outcome of trabeculectomy at 12 months follow-up and to examine the balance of benefit and harms when compared to any other anti-scarring agents or no additional anti-scarring agents. SEARCH METHODS: We searched CENTRAL (which contains the Cochrane Eyes and Vision Trials Register) (2015, Issue 10), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to November 2015), EMBASE (January 1980 to November 2015), the ISRCTN registry (www.isrctn.com/editAdvancedSearch), ClinicalTrials.gov (www.clinicaltrials.gov) and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 12 November 2015. SELECTION CRITERIA: We included randomised controlled trials (RCTs) of anti-VEGF therapies administered by subconjunctival injection compared to any other anti-scarring agents or no additional anti-scarring agents (no treatment or placebo) in trabeculectomy surgery. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. Our primary outcome was successful trabeculectomy at 12 months after surgery which was defined as achieving a target IOP (usually no more than 21 mm Hg) without any additional intervention. Other outcomes included: qualified success (achieving target IOP with or without additional intervention), mean IOP and adverse events. MAIN RESULTS: We included five RCTs (175 participants, 177 eyes) that met the inclusion criteria in this review.One trial conducted in Iran (37 participants, 37 eyes) compared anti-VEGF (bevacizumab 0.2 mg) versus control (sham injection) in people with refractory glaucoma. We judged this study to be at low risk of bias.The primary outcome of this review was not reported; mean IOP at three months was 15.1 mm Hg (standard deviation 1.0) in both anti-VEGF and control groups.Four trials compared anti-VEGF to mitomycin C (MMC) (138 particpants, 140 eyes). These studies were conducted in India, Iran, Turkey and the USA. The anti-VEGF agent used in these four trials was bevacizumab 2.5 mg (two trials), bevacizumab 1.25 mg three times and ranibizumab 0.5 mg. Two trials were at high risk of bias in two domains and one trial was at high risk of bias in four domains.Only one of these trials reported the primary outcome of this review (42 participants, 42 eyes). Low quality evidence from this trial showed that people receiving bevacizumab 2.5 mg during primary trabeculectomy were less likely to achieve complete success at 12 months compared to people receiving MMC but the confidence interval (CI) was wide and compatible with increased chance of complete success for anti-VEGF (risk ratio (RR) 0.71, 95% CI 0.46 to 1.08), Assuming that approximately 81% of people receiving MMC achieve complete success, the anticipated success using anti-VEGF agents would be between 37.2% and 87.4%. The same trial suggested no evidence for any difference in qualified success between bevacizumab and MMC (RR 1.00, 95% CI 0.87 to 1.14, moderate quality evidence). Two trials of primary trabeculectomy provided data on mean IOP at 12 months; one trial of bevacizumab 2.5 mg and one trial of ranibizumab 0.5 mg. Mean IOP was 1.86 mm Hg higher (95% CI 0.15 to 3.57) in the anti-VEGF groups compared to the MMC groups (66 people, low quality evidence). Data were reported on wound leak, hypotony, shallow anterior chamber and endophthalmitis, but these events occurred rarely and currently there are not enough data available to detect any differences, if any, between the two treatments. AUTHORS' CONCLUSIONS: The evidence is currently of low quality which is insufficient to refute or support anti-VEGF subconjunctival injection for control of wound healing in glaucoma surgery. The effect on IOP control of anti-VEGF agents in glaucoma patients undergoing trabeculectomy is still uncertain, compared to MMC.Further RCTs of anti-VEGF subconjunctival injection in glaucoma surgery are required, particularly compared to sham treatment with at least 12 months follow-up.

[Positive regulation in expression of the phenazine-producing operon phz2 mediated by pip in Pseudomonas aeruginosa PAO1].

UNLABELLED: Pseudomonas aeruginosa PAO1, an opportunistic pathogenic bacterium, produces phenazine and its derivatives which play a critical role in pathogen-host interaction during its infection. In a biological control strain P. chlororaphis PCL1391, Pip positively regulates PCN production. OBJECTIVE: Our aim is to identify the function and regulation of an ORF of PA0243 (the homolog of Pip) in Pseudomonas aeruginosa PAO1. METHODS: We first cloned the fragment of the pip gene from the chromosomal DNA of P. aeruginosa PAO1 and constructed the pip-defect mutant PA-PG with the insertion of gentamycin resistance cassette (aacC1). With construction and introduction of pME10P (containing the whole pip gene region) , complementation of the pip was then carried out. With creation of the mutants PA-PD-Z1G and PA-PG-Z2K, phenazine-1-carboxylic acid and pyocyanin were measured in GA medium in relative mutants, respectively. RESULTS: In GA medium, production of phenazine-1-carboxylic acid and pyocyanin in the mutant PA-PG decreased dramatically in comparison with that produced in the wild type strain PAO1. The amounts of phenazine-1-carboxylic acid and pyocyanin, however, were recovered with complementation of the derivative PA-PG bearing pME10P. The production of phenazine-1-carboxylic acid and pyocyanin in mutant PA-PG-Z2K were same to those in parental strain PA-Z2K. Phenazine-1-carboxylic acid and pyocyanin produced by the mutant PA-PD-Z1G were lower than those in the original strain PA-Z1G. CONCLUSION: With these results, it is suggested that Pip exerts positively regulation in phenazine biosynthesis by specifically modulating expression of the phz2 operon, not by mediating expression of the phzl operon in P. aeruginosa PAO1.

The prevalence of visual impairment in older adults in mainland China: a systematic review and meta-analysis.

PURPOSE: This paper presents estimates of the prevalence of blindness and low vision among older adults over 50 years of age in mainland China. METHODS: All primary reports of population-based studies that reported the prevalence or incidence of visual impairment among older populations in mainland China were identified. Twenty-four population-based studies were included in this systematic review. Blindness is defined as visual acuity of less than 3/60, or a corresponding visual-field loss to less than 10 degrees in the better eye with the best possible correction; low vision is defined as visual acuity of less than 6/18, but equal to or better than 3/60 in the better eye with the best possible correction. The pooled prevalence estimates of blindness and low vision were calculated assuming a random-effects model. Relative odds with 95% confidence intervals (95% CIs) were calculated, stratified by methodological and socioeconomic variables. RESULTS: The overall pooled prevalence of blindness was 1.7% (95% CI 1.4-2.1). The results of the meta-regression showed the significance of a predictor variable: geographic region. The blindness rates per 100 older adults in various regions were 1.4 (0.9-2.0) in East China, and 1.4 (1.0-2.0) in Central China and 2.5 (1.9-3.2) in Western China. The overall pooled prevalence of low vision was 4.1% (3.4-5.1) and the independent pooled prevalence rates stratified by geographic region were 3.6% (2.6-5.1) in East China, 3.6% (2.4-5.2) in Central China and 5.2% (3.6-7.4) in Western China. CONCLUSIONS: Blindness or low vision affects approximately 5.8% Chinese adults older than 50 years. The prevalence of visual impairment, and especially blindness, vary greatly by the developmental status of geographic region.

The prevalence of primary glaucoma in mainland China: a systematic review and meta-analysis.

OBJECTIVE: To estimate the prevalence of primary glaucoma in mainland China and to quantify its association with age, sex, and region. METHODS: Population-based studies that reported the prevalence of primary open-angle glaucoma (POAG) or/and primary angle-closure glaucoma (PACG) among adult populations in mainland China were identified through systematic searches. Fourteen articles providing 12 population-based studies were included. The overall pooled prevalence estimates were calculated using a random-effects model. A logistic metaregression was used to model the associations between the odds ratio (OR) and 95% confidence interval of primary glaucoma and age, sex, and region. RESULTS: The overall pooled prevalence of POAG was 0.7% (95% confidence interval, 0.4-1.2), and PACG was found in 1.4% (1.0%, 1.7%). The OR per decade increase in age was 1.68 (1.12, 2.52) for POAG, and 2.11 (1.72, 2.60) for PACG. The OR of POAG prevalence was 0.65 (0.26, 1.62) between men and women. Chinese women were 1.75 (1.20, 2.56) times more likely than men to have PACG. The OR between western China and east China were 0.37 (0.10, 1.35) for POAG, and 1.06 (0.63, 1.76) for PACG. The OR between urban China and rural China were 3.92 (1.55, 9.92) for POAG, and 1.07 (0.55, 2.10) for PACG. CONCLUSIONS: The prevalence of PACG was approximately double that of POAG in adult Chinese. The rate of change of PACG prevalence with age increased more rapidly than that of POAG. The prevalence of POAG in urban was higher than that in rural. PACG was more common in women than in men.

Intraocular pressure-lowering effects of commonly used fixed-combination drugs with timolol: a systematic review and meta-analysis.

BACKGROUND: The first goal of medical therapy in glaucoma is to reduce intraocular pressure (IOP), and the fixed-combination medications are needed to achieve sufficiently low target IOP. The aim of this systematic review and meta-analysis is to evaluate IOP-lowering effect of the commonly used fixed-combination drugs containing 0.5% timolol. METHODS: Pertinent publications were identified through systematic searches. Over 85% of the patients had to be diagnosed with primary open-angle glaucoma (POAG) or ocular hypertension (OHT). Forty-one randomized clinical trials were included in the meta-analysis. The main efficacy measures were the absolute and relative values of mean diurnal IOP reduction, and the highest and lowest IOP reductions on the diurnal IOP curve. The pooled 1- to 3-month IOP-lowering effects after a medicine-free washout period was calculated by performing meta-analysis using the random effects model, and relative treatment effects among different fixed combinations were assessed using a mixed-effects meta-regression model. RESULTS: The relative reductions for mean diurnal IOP were 34.9% for travoprost/timolol, 34.3% for bimatoprost/timolol, 33.9% for latanoprost/timolol, 32.7% for brinzolamide/timolol, 29.9% for dorzolamide/timolol, and 28.1% for brimonidine/timolol. For the highest IOP decrease, relative reductions ranged from 31.3% for dorzolamide/timolol to 35.5% for travoprost/timolol; for the lowest IOP decrease, those varied from 25.9% for dorzolamide/timolol to 33.1% for bimatoprost/timolol. Both latanoprost/timolol and travoprost/timolol were more effective in lowering mean diurnal IOP than brimonidine/timolol (WMD: 5.9 and 7.0) and dorzolamide/timolol (WMD: 3.8 and 3.3). CONCLUSIONS: All six commonly used fixed-combination drugs containing timolol can effectively lower IOP in patients with POAG and OHT, and both latanoprost/timolol and travoprost/timolol might achieve better IOP-lowering effects among the six fixed-combination agents.

Myocilin polymorphisms and primary open-angle glaucoma: a systematic review and meta-analysis.

BACKGROUND: Glaucoma is the leading cause of irreversible blindness in the world. Recent evidence indicates a role for genetic susceptibility to primary open-angle glaucoma (POAG). The relation between myocilin polymorphisms and POAG susceptibility has been studied in different populations. METHODS: A meta-analysis of 32 published genetic association case-control studies, which examined the relation between POAG and the R46X, R76K, Y347Y, T353I, and Q368X polymorphisms of the myocilin gene, was carried out. RESULTS: In meta-analysis, significant associations were observed between POAG risk and two myocilin polymorphisms with summarized odds ratio of 4.68 (95%CI, 2.02-10.85) for Q368X and 2.17 (95% CI, 1.32-3.57) for T353I. Both Q368X and T353I were significantly associated with high-tension glaucoma, with summarized odds ratio of 4.26 (1.69, 10.73) and 2.26 (1.37-3.72). In Westerners, significant association was observed for Q368X mutation (odds ratio, 5.17; 95% CI, 2.16-12.40). However, in Asians it was for T353I (odds ratio, 2.17; 95% CI, 1.32-3.57). CONCLUSIONS: There is strong evidence that myocilin polymorphisms are associated with POAG susceptibility, and the prevalence of myocilin mutations might be ethnicity-dependent in Caucasians for Q368X and in Asians for T353I.

Effect of intravitreal anti-vascular endothelial growth factor therapy on the risk of arterial thromboembolic events: a meta-analysis.

BACKGROUND: Intravitreal anti-vascular endothelial growth factor (VEGF) monoclonal antibodies are used in ocular neovascular diseases. A consensus has emerged that intravenous anti-VEGF can increase the risk of arterial thromboembolic events. However, the role of intravitreal anti-VEGF in arterial thromboembolism is controversial. Therefore, we did a systematic review and meta-analysis to investigate the effects of intravitreal anti-VEGF on the risk of arterial thromboembolic events. METHODS: Electronic databases were searched to identify relevant randomized clinical trials comparing intravitreal anti-VEGF with controls. Criteria for inclusion in our meta-analysis included a study duration of no less than 12 months, the use of a randomized control group not receiving any intravitreal active agent, and the availability of outcome data for arterial thromboembolic events, myocardial infarction, cerebrovascular accidents, and vascular death. The risk ratios and 95% CIs were calculated using a fixed-effects or random-effects model, depending on the heterogeneity of the included studies. RESULTS: A total of 4942 patients with a variety of ocular neovascular diseases from 13 randomized controlled trials were identified and included for analysis. There was no significant difference between intravitreal anti-VEGF and control in the risk of all events, with risk ratios of 0.87 (95% CI, 0.64 to 1.19) for arterial thromboembolic events, 0.96 (95% CI, 0.55-1.68) for cerebrovascular accidents, 0.69 (95% CI 0.40-1.21) for myocardial infarctions, and 0.68 (95% CI, 0.37-1.27) for vascular death. CONCLUSIONS: The strength evidence suggests that the intravitreal use of anti-VEGF antibodies is not associated with an increased risk of arterial thromboembolic events.

Meta-analysis of α2-adrenergic agonists versus carbonic anhydrase inhibitors as adjunctive therapy.

OBJECTIVE: To evaluate the efficacy of α2-adrenergic agonist (AA) brimonidine and topical carbonic anhydrase inhibitors (CAIs) dorzolamide and brinzolamide in reducing intraocular pressure (IOP) when used as adjunctive therapy to ß-blockers (BBs) or prostaglandin analogs (PGAs). RESEARCH DESIGN AND METHODS: Pertinent publications were identified through systematic searches of PubMed, EMBASE, and the Cochrane Controlled Trials Register. Randomized controlled trials comparing AA with CAIs in patients with primary open-angle glaucoma (POAG) or ocular hypertension (OHT) who had inadequate IOP control with monotherapy of a BB or PGA. The weighted mean differences (WMD) of IOP-lowering efficacy were calculated by performing meta-analysis. MAIN OUTCOME MEASURES: The main efficacy measures were the reduction from baseline to end of treatment in IOP at peak, trough, and diurnal curve. RESULTS: Eleven published randomized clinical trials involving 1493 patients were included in the meta-analysis. As adjunctive therapy, the IOP reduction was greater in the brimonidine group than in the CAI group at peak (WMD: 0.99 mmHg [95% confidence interval, 0.45 to 1.53]) and diurnal curve (WMD: 0.62 mmHg [0.07 to 1.18]). As adjunctive therapy to BBs, brimonidine was more effective than CAIs in reducing IOP at peak (WMD: 0.85 mmHg [0.42 to 1.29]) and trough (WMD: 0.47 mmHg [0.12 to 0.83]). As adjunctive therapy to PGAs, brimonidine resulted greater reduction in peak IOP than CAIs (WMD: 1.04 mmHg [0.08 to 2.00]). CONCLUSIONS: Brimonidine provides greater IOP-lowering efficacy than topical carbonic anhydrase inhibitors as adjunctive therapy to BBs or PGAs.

Systematic overview of the efficacy of nonpenetrating glaucoma surgery in the treatment of open angle glaucoma.

BACKGROUND: To evaluate the intraocular pressure (IOP)-lowering effects achieved by nonpenetrating glaucoma surgery (NPGS) and its modifications in patients with open angle glaucoma. MATERIAL/METHODS: Randomized controlled trials evaluating patients with primary and secondary open angle glaucoma treated with NPGS were identified through systematic searches. The main outcome measures were the percentage IOP reduction and the complete success rate. Complete success was defined as target endpoint IOP (usually less than 21 mm Hg) without medications. The pooled estimates were calculated using the random effects model. RESULTS: Both deep sclerectomy (DS) and viscocanalostomy (VCO) were less effective than trabeculectomy (TE) in lowering IOP, with the percentage IOP reductions at 2 years being 35.2% for DS, 30.2% for VCO, and 45.6% for TE. Intraoperative use of implants and mitomycin C (MMC) increased IOP-lowering effects of DS, with IOP reductions at 2 years of 41.1% and 41.7%, respectively. The complete success rates at 4 years were 35.4% for DS, and 22.7% for VCO, lower than that of TE (47.6%). The complete success rates of DS with implants and MMC of 64.6% and 52.1%, respectively, at 4 years, were greater than that of primary DS. NPGS caused major complications in fewer patients than did TE. CONCLUSIONS: Primary deep sclerectomy and primary viscocanalostomy, which can significantly lower IOP, were associated with fewer complications than was TE. However, the IOP-lowering effects of both NPGS seem to be lower than that of primary TE. The efficacy of DS can be improved with the intraoperative use of implants and MMC.