Gender-specific lncRNA-miRNA-mRNA regulatory network to reveal potential genes for primary open-angle glaucoma.

BACKGROUND: Investigation of biomarkers may facilitate understanding the mechanisms of primary open-angle glaucoma (POAG) and developing therapeutic targets. This study aimed to identify potential genes based on competing endogenous RNA (ceRNA) network for POAG. METHODS: Based on long noncoding RNAs (lncRNAs), microRNAs (miRNAs) and messenger RNAs (mRNAs) from the Gene Expression Omnibus (GEO) database, we identified differential expressed lncRNAs (DELs), differential expressed miRNAs (DEMis) and differential expressed mRNAs (DEMs) and then constructed a ceRNA network. Through weighted gene co-expression network analysis (WGCNA), we identified gender-specific genes for gender-associated ceRNA network construction, followed by the protein-protein interaction (PPI) network and functional enrichment analysis to screen hub genes and reveal their functions. The expression levels of hub genes were measured in steroid-induced ocular hypertension (SIOH) mice. RESULTS: A total of 175 DELs, 727 DEMs and 45 DEMis were screened between control and POAG samples. Seven modules were identified through WGCNA and one module was associated with gender of POAG patients. We discovered 41 gender-specific genes for gender-associated ceRNA construction and then identified 8 genes (NAV3, C1QB, RXRB, P2RY4, ADAM15, VAV3, ZNF207 and TOP1), which were enriched in cell cycle-related pathways and immune-related pathways. C1QB, RXRB, Top1 and ZNF207 were highly interacted with other proteins. The expression levels of NAV3 and C1QB were downregulated in SIOH, while the levels of RXRB, P2RY4, ADAM15, VAV3, ZNF207 and TOP1 were upregulated in SIOH. CONCLUSION: This study identifies hub genes associated with the pathogenesis of gender-specific POAG and provides potential biomarkers for POAG.

Chronic hypotony management using endoscopy-assisted vitrectomy after severe ocular trauma or vitrectomy.

AIM: To report outcomes of endoscopy-assisted vitrectomy (EAV) in patients with chronic hypotony following severe ocular trauma or vitrectomy. METHODS: This was a retrospective, noncomparative case series. Ciliary bodies were evaluated using ultrasound biomicroscopy pre-operatively and direct visualisation intraoperatively. All selected individuals (seven patients/seven eyes) underwent EAV. Removal of ciliary membrane and traction, gas/silicone oil tamponade (GT/SOT), and scleral buckling (SB) were performed in selected eyes. Outcome measurements mainly included intraocular pressure (IOP) and best-corrected visual acuity (BCVA). RESULTS: Seven eyes from 7 male aphakic patients with a mean age of 45 (range, 20-68)y were included in this study; the average follow-up time was 12 (9-15)mo. GT was performed in 2 eyes; membrane peeling (MP) and SOT in 2 eyes; and MP, SOT, and SB in 3 eyes. The mean pre- and post-operative IOP were 4.5 (range, 4.0±0.11 to 4.8±0.2) mm Hg and 9.9 (range, 5.6±0.17 to 12.1±0.2) mm Hg at 52wk (12mo), respectively. BCVA improved in six eyes; one eye still showed light perception, and no bulbi phthisis was observed. CONCLUSION: Endoscopy offers improved judgment and recognition and has an improved prognosis for chronic hypotony. Therefore, endoscopy can be an effective and promising operative technique for chronic traumatic hypotony management.

A nomogram for predicting risk of death during hospitalization in elderly patients with Alzheimer's disease at the time of admission.

Background and objectives: Elderly patients with Alzheimer's disease (AD) often have multiple underlying disorders that lead to frequent hospital admissions and are associated with adverse outcomes such as in-hospital mortality. The aim of our study was to develop a nomogram to be used at hospital admission for predicting the risk of death in patients with AD during hospitalization. Methods: We established a prediction model based on a dataset of 328 patients hospitalized with AD -who were admitted and discharged from January 2015 to December 2020. A multivariate logistic regression analysis method combined with a minimum absolute contraction and selection operator regression model was used to establish the prediction model. The identification, calibration, and clinical usefulness of the predictive model were evaluated using the C-index, calibration diagram, and decision curve analysis. Internal validation was evaluated using bootstrapping. Results: The independent risk factors included in our nomogram were diabetes, coronary heart disease (CHD), heart failure, hypotension, chronic obstructive pulmonary disease (COPD), cerebral infarction, chronic kidney disease (CKD), anemia, activities of daily living (ADL) and systolic blood pressure (SBP). The C-index and AUC of the model were both 0.954 (95% CI: 0.929-0.978), suggesting that the model had accurate discrimination ability and calibration. Internal validation achieved a good C-index of 0.940. Conclusion: The nomogram including the comorbidities (i.e., diabetes, CHD, heart failure, hypotension, COPD, cerebral infarction, anemia and CKD), ADL and SBP can be conveniently used to facilitate individualized identification of risk of death during hospitalization in patients with AD.

Changes of plasma aldosterone and angiotensin II levels in patients with ischemic cardiomyopathy combined with Type-2 diabetes mellitus and their clinical significance.

Objective: To analyze the changes of plasma aldosterone (ALD) and angiotensin II (Ang II) levels in patients with ischemic cardiomyopathy (ICM) combined with Type-2 diabetes mellitus (T2DM) and their clinical significance. Methods: Sixty-eight patients with ICM combined with T2DM and fifty-two patients with simple ICM treated in the People's Hospital of Three Gorges University/the First People's Hospital of Yichang from February 2018 to February 2021 were selected as observation group and control group, respectively. All the patients had intervention with the same neuroendocrine hormone regime. The plasma ALD and Ang II and left ventricular function indexes (left ventricular ejection fraction (LVEF), left ventricular end-diastolic diameter (LVEDD) and left ventricular end-systolic diameter (LVESD)] were measured and compared between the two groups before and after treatment. The correlations of plasma ALD and Ang-II with left ventricular function before treatment were analyzed using Pearson's correlation analysis. The diagnostic efficacy of plasma ALD and Ang-II in ICM and T2DM was evaluated by the receiver operating characteristic (ROC) curve. Results: Before treatment, the plasma ALD and Ang II levels in the observation group were (184.42 ± 56.75) ng/L and (46.68 ± 12.16) ng/L, respectively, which were significantly higher than those in the control group [(165.03 ± 45.67) ng/L and (39.70 ± 10.69) ng/L, p< 0.05]. Compared with before treatment, ALD level increased significantly in the observation group while decreased significantly in the control group after treatment (p< 0.05). After treatment, Ang-II level reduced significantly while LVEF increased significantly in both groups (p< 0.05). After treatment, plasma ALD and LVESD in the observation group were significantly higher than those in the control group (p< 0.05), but plasma Ang II level, LVEF and LVEDD showed no statistically significant differences between the two groups (p> 0.05). Before treatment, plasma ALD and Ang II were negatively correlated with LVEF (p< 0.05). Before treatment, the area under the curve (AUC) of plasma ALD and Ang II levels in diagnosing ICM combined with T2DM were 0.689 and 0.704, respectively. Conclusion: The plasma levels of ALD and Ang-II in patients with ICM combined with T2DM increase significantly, and their diagnostic value is not high. Compared with patients with simple ICM, the decrease in plasma ALD and Ang- II levels is less obvious after the same intervention, but it is still conducive to the improvement of cardiac function.

Association between helicobacter pylori infection and subclinical atherosclerosis: A systematic review and meta-analysis.

BACKGROUND: The relationship between Helicobacter pylori (H. pylori) infection and subclinical atherosclerosis has been confirmed, but these conclusions are still controversial. Therefore, we have performed a systematic review and meta-analysis to assess the association between H. pylori infection and subclinical atherosclerosis. METHODS: Databases including PubMed, Embase, Web of Science were searched for the articles on the association of carotid intima-media thickness or pulse wave velocity with H. pylori infection published up to January 1, 2020. Stata 12.0 was used to calculate standardized mean difference (SMD) and 95% confidence interval (95% CI); the I2 test was used to evaluate heterogeneity between studies and sensitivity analysis and subgroup analysis were used to explore the source of heterogeneity. Funnel plot, Begg test, and Egger test were used to estimate publication bias. RESULTS: Data were extracted from 18 studies involving 6776 subjects with H. pylori positive and 7794 with H. pylori negative. H. pylori positive subjects is significantly associated with increased subclinical atherosclerosis as determined by carotid intima-media thickness (SMD: 0.376 mm; 95% CI: 0.178, 0.574; P < .001, I2 = 90.6%), pulse wave velocity (SMD: 0.320 m/s; 95% CI: 0.242, 0.398; P < .001, I2 = 52.6%), compared with H. pylori negative. Similar results were observed when subgroups analysis were stratified according to age, male ratio, geographical location, H. pylori diagnosis, and study design. Sensitivity analyses showed that our results were robust. The Begg test or Egger test showed no significant publication bias (all P > .05). CONCLUSIONS: This meta-analysis confirmed a significant association between H. pylori and subclinical atherosclerosis, which will help H. pylori patients to establish effective strategies for the prevention and control of cardiovascular events.

Long-term subcutaneous injection of lipopolysaccharides and high-fat diet induced non-alcoholic fatty liver disease through IKKε/ NF-κB signaling.

Non-alcoholic fatty liver disease (NAFLD) was associated with increased level of lipopolysaccharides (LPS) which mechanism remained unclear on intervention between LPS and NAFLD. The aim was to explore the IKKε/NF-κB role and its intervention of LPS and high-fat diet (HFD) induced NAFLD. Male C57BL/6 mice were fed on high-fat diet (HFD) combined with or without simultaneously subcutaneous injection of LPS for 18 weeks. Body weight , blood biochemistry parameters, inflammatory mediator and liver lipid deposition were measured to evaluate LPS effect on NAFLD. Furthermore, IKKε selective inhibitor amlexanox (AM) was administrated by gavage to HFD + LPS induced mice. The indicators about metabolism and inflammation were examined and qRT-PCR, immunoblotting assay as well as immunohistochemistry were performed to assess IKKε/NF-κB activation and downstream gene expression. This study found that low-dose LPS + HFD aggravated more significant steatosis than simple HFD or high-dose LPS + HFD. Low-dose LPS exacerbated more prominent inflammation profile including increased IKKε and NF-κB expression in liver than HFD. Inhibiting IKKε/NF-κB signaling with amlexanox significantly prevented HFD + LPS induced metabolic disorders and hepatic steatosis. LPS-upregulated gene expression involved in glucolipid metabolism could be downregulated by amlexanox. Thus, the present study confirmed long-term combinational administration of subcutaneous low-dose LPS injection and HFD induced NAFLD model which had more significant phenotype in mice than simple HFD or high-dose LPS-induction. Targeting on IKKε/NF-κB signaling with its inhibitor amlexanox alleviated steatohepatitis, suggesting that IKKε/NF-κB signaling was responsible for effect of LPS and HFD on NAFLD.

Amlexanox reversed non-alcoholic fatty liver disease through IKKε inhibition of hepatic stellate cell.

AIMS: Amlexanox, an inhibitor of nuclear factor κB kinase epsilon (IKKε) and TANK-binding kinase 1(TBK1), was demonstrated to be effective in diabetes and obesity. The aim of this study was to explore the molecular mechanisms of its role in non-alcoholic fatty liver disease (NAFLD). MAIN METHODS: NAFLD mouse models were established by using eight-week-old male C57BL/6 mice fed with high-fat diet (HFD) or (and) lipopolysaccharide (LPS) for 18 weeks. From the beginning of HFD, HFD-induced mice were subjected to amlexanox or vehicle for 18 weeks. HFD + LPS-induced mice were treated with amlexanox or vehicle for the last 6 weeks. Blood biochemistry parameters were determined using automatic biochemistry analyzer. Histological changes of liver tissue were observed by hematoxylin-eosin (H&E) staining and Oil Red O staining. The expressions of IKKε and smooth muscle actin-α (α-SMA) were evaluated through immunohistochemistry. Serum inflammatory mediator was determined by enzyme linked immunosorbent assay (ELISA). Gene expressions involved in glucose and lipid metabolism, insulin signaling pathway were examined using quantitative RT-PCR or Western blotting. KEY FINDINGS: This study demonstrated that amlexanox reversed glucose and lipid metabolic disturbance and hepatic steatosis in NAFLD mice model. IKKε was specific expressed in hepatic stellate cells (HSCs) instead of hepatocytes. This study also found that amlexanox improved insulin signaling (Insulin-IRS-1-Akt) in hepatocytes through inhibiting inflammation (IKKε-NF-κB-TNF-α/IL-1α) in HSCs. SIGNIFICANCE: The present study confirmed that IKKε was specific expressed in HSCs. Inhibition of activated HSCs was responsible for effects of amlexanox on NAFLD, with improving insulin signal pathway in hepatocytes.

Protective effects of lipoic acid-niacin dimers against blue light-induced oxidative damage to retinal pigment epithelium cells.

AIM: To evaluate the protective effects of lipoic acid-niacin (N2L) dimers against blue light (BL)-induced oxidative damage to human retinal pigment epithelium (hRPE) cells in vitro. METHODS: hRPE cells were divided into a control group (CG), a BL group, an N2L plus BL irradiation group, an α-lipoic acid (ALA) plus BL group, an ALA-only group, and an N2L-only group. hRPE cellular viability was detected by performing 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium (MTT) bromide assays, and apoptosis was evaluated by annexin-V-PE/7-AAD staining followed by flow cytometry. Ultrastructural changes in subcellular organelles were observed by transmission electron microscopy. Reactive oxygen species formation was assayed by flow cytometry. The expression levels of the apoptosis-related proteins BCL-2 associated X protein (BAX), B-cell leukmia/lymphoma 2 (BCL-2), and caspase-3 were quantified by Western blot analysis. RESULTS: BL exposure with a light density of 4±0.5 mW/cm2 exceeding 6h caused hRPE toxicity, whereas treatment with a high dose of N2L (100 mol/L) or ALA (150 mol/L) maintained cell viability at control levels. BL exposure caused vacuole-like degeneration, mitochondrial swelling, and reduced microvillus formation; however, a high dose of N2L or ALA maintained the ultrastructure of hRPE cells and their organelles. High doses of N2L and ALA also protected hRPE cells from BL-induced apoptosis, which was confirmed by Western blot analysis: BCL-2 expression significantly increased, while BAX and caspase-3 expression slightly decreased compared to the CG. CONCLUSION: High-dose N2L treatment (>100 mol/L) can reduce oxidative damage in degenerating hRPE cells exposed to BL with an efficacy similar to ALA.

Protection of tight junction between RPE cells with tissue factor targeting peptide.

AIM: To investigate the effect of tissue factor targeting peptide (TF-TP) on retinal pigment epithelium (RPE) cells tight junctions. METHODS: Cell counting kit-8 (CCK-8) was used to measure the proliferation of ARPE-19 cells. Expression of tight junction, ZO-1 in ARPE-19 cells was measured by Western blot and immunofluorescent staining. Western blot was also used to detect the expression of tissue factor (TF). CEC Transmigration Assay was used to measure the migration of ARPE-19 cells. The transport of fluorescent markers [fluorescein isothiocyanate dextrans of 4, 10, 20 (FD4, FD10, FD20)] and the transepithelial electrical resistance (TEER) were used to measure in ARPE-19 cell. RESULTS: CCK-8 assay showed that 5 µmol/L TF-TP can inhibit ARPE-19 cells abnormally proliferation stimulated by lipopolysaccharide (LPS; P<0.05). LPS increased the transport of fluorescent markers (FD4, FD10, FD20) and decreased TEER levels in ARPE-19 cells, respectively, which were prevented by 5 µmol/L TF-TP pretreatment (P<0.05). Furthermore, LPS significantly up-regulated the expression of TF and downregulated the expression of ZO-1 (P<0.05) in ARPE-19 cell which was inhibited by the TF-TP (P<0.05). In addition, TF-TP inhibited the abnormal migration induced by LPS in ARPE-19 cell (P<0.05). CONCLUSION: Our findings suggest that TF-TP suppressed proliferation and migration of ARPE-19 cells induced by LPS, and maintained the RPE tight junctions through inhibition of TF expression and increased expression of ZO-1.

Endoscopy-assisted vitrectomy in the anterior vitreous.

Endoscopy-assisted ocular surgery is a relatively old technique that is increasingly being recognized for its application in cases of vitreoretinal disease. This technique is especially useful when both the vitreous and retina are difficult to access because of media opacity, a small pupil, or a microcornea. In this context, the anterior vitreous is often difficult to dissect because of its complex pathological changes. This article reviews the common anatomical features and pathologies that are observed in the anterior vitreous, as well as the applications and indications of endoscopy-assisted vitrectomy in the anterior vitreous.

Non-invasive markers of cardiovascular risk in patients with subclinical hypothyroidism: A systematic review and meta-analysis of 27 case control studies.

It has been reported that subclinical hypothyroidism (SCH) is closely related to subclinical atherosclerosis. According to the impact of SCH on noninvasive markers of cardiovascular risk, we fulfilled a meta-analysis of included studies to provide an integrated overview. We searched electronic databases and included all relevant studies involving SCH and epicardial adipose tissue (EAT), carotid intima-media thickness (CIMT), pulse wave velocity (PWV), flow-mediated dilation (FMD) and glyceryl trinitrate-induced dilation (GNT- induced dilation). The result was calculated in a meta-analysis to assess the impact of SCH on these markers. A total of 27 studies were entered in the final analysis. Compared with euthyroid subjects, SCH patients exhibited a significantly increased CIMT (SMD: 0.369 mm; 95%CI: 0.038, 0.700; P = 0.029) and EAT (SMD: 1.167 mm; 95%CI: 0.869, 1.466; P = 0.000) and increased PWV (SMD: 3.574 m/s; 95%CI: 0.935, 6.213, P = 0.008). We also found significantly lower FMD (SMD: -1.525%, 95%CI: -2.156, -0.894, P = 0.000) and lower GNT-induced dilation (SMD: -0.384%, 95%CI: -0.625, -0.142, P = 0.002). Sensitivity analysis and subgroup analysis confirmed the above results. Our meta-analysis confirmed a significant association of SCH and cardiovascular risk with arterial wall thickening and stiffening and endothelial dysfunction. These findings will help to establish detailed cardiovascular prevention strategies for SCH patients.

Clinical effectiveness and cost-effectiveness of nurse-led care in Chinese patients with rheumatoid arthritis: A randomized trial comparing with rheumatologist-led care.

BACKGROUND AND AIM: The concept of nurse-led care (NLC) was not familiar in China. This study was designed to evaluate the clinical effectiveness and cost-effectiveness of NLC versus rheumatologist-led care (RLC) in Chinese patients with rheumatoid arthritis (RA). METHODS: Patients of either gender (aged ≥18 years) with RA were enrolled at Wenhai Central Hospital, China (January 2015 to December 2015). The participants were then randomized to NLC or RLC. Outcomes of both the groups were compared in terms of effectiveness by measuring the Disease Activity Score 28, visual analogue scores pertaining to pain and fatigue, and duration of morning stiffness. Costs associated with resource use for RA were assessed and compared between both groups. RESULTS: A total of 214 RA patients in 2 groups (n = 107 in each group) were enrolled and analysed. Improvements in clinical outcomes (disease activity, pain, fatigue, and morning stiffness) over 12 months were significantly greater in the NLC group compared to RLC (P < 0.001). Overall, costs associated with resource use were higher in the RLC group compared to the NLC group (P < 0.05). CONCLUSIONS: Our preliminary finding suggested that RA patients managed by NLC compared to RLC may have better clinical outcomes and more cost-effective care in China.

[Association between hepatocyte growth factor in tears and corneal haze in rabbits early after epipolis laser in situ keratomileusis].

OBJECTIVE: To study the dynamic changes of levels of hepatocyte growth factor (HGF) in tears and their association with corneal haze in rabbits early after epipolis laser in situ keratomileusis (Epi-LASIK). METHODS: Twenty-four New Zealand rabbits received Epi-LASIK with an ablation depth of 100 µm in one eye and of 150 µm in the other eye. Before and at 3, 7, 14, and 30 days after the surgery, the level of HGF in tears collected from the rabbits was measured using enzyme-linked immunosorbent assay (ELISA), and corneal haze was graded after surgery. RESULTS: In all the rabbits, corneal epithelium healing occurred in 3 to 5 days after Epi-LASIK. Corneal haze appeared 3 days postoperatively in the rabbits accompanied by increased levels of HGF in tears. At 3, 7, 14, and 30 days after the surgery, the rabbits with an ablation depth of 150 µm showed more obvious corneal haze (P<0.05) and significantly higher levels of HGF in tears than those with an ablation depth of 100 µm (P<0.05). CONCLUSION: In rabbits receiving Epi-LASIK, HGF levels in tears and the grade of corneal haze show a positive correlation early after the surgery and are both related with the depth of ablation.

Effect of Probiotics on Glucose and Lipid Metabolism in Type 2 Diabetes Mellitus: A Meta-Analysis of 12 Randomized Controlled Trials.

BACKGROUND It has been unclear whether supplemental probiotics therapy improves clinical outcomes in type 2 diabetic patients. This meta-analysis aimed to summarize the effect of probiotics on glucose and lipid metabolism and C-reactive protein (CRP) from 12 randomized controlled trials (RCTs). MATERIAL AND METHODS An up-to-date search was performed for all relevant RCTs up to April 2016 from PubMed, Embase, and Cochrane Library. Standardized mean difference (SMD) and weighted mean difference (WMD) were calculated for a fixed-effect and random-effect meta-analysis to assess the impact of supplemental probiotics on fasting plasma glucose (FPG), glycated hemoglobin (HbA1c), fasting insulin, homeostasis model assessment of insulin resistance (HOMA-IR), lipid profile, and CRP level. RESULTS A total of 12 studies (684 patients) were entered into the final analysis. The effect of probiotics was significant on reducing HbA1c level (standardized mean difference [SMD], -0.38; confidence interval [CI], -0.62 to -0.14, P=0.002; I²=0%, P=0.72 for heterogeneity), fasting insulin level (SMD, -0.38; CI -0.59 to -0.18, P=0.0003; I²=0%, P=0.81 for heterogeneity), and HOMA-IR (SMD, -0.99; CI -1.52 to -0.47, P=0.0002; I²=86%, P<0.00001 for heterogeneity). Pooled results on effects of probiotics on FPG, CRP, or lipid profile were either non-significant or highly heterogeneous. CONCLUSIONS This meta-analysis demonstrated that probiotics supplementation was associated with significant improvement in HbA1c and fasting insulin in type 2 diabetes patients. More randomized placebo-controlled trials with large sample sizes are warranted to confirm our conclusions.

Prognostic Value of High-Sensitivity C-Reactive Protein, Procalcitonin and Pancreatic Stone Protein in Pediatric Sepsis.

BACKGROUND To investigate the prognostic value of procalcitonin (PCT), high-sensitivity C-reactive protein (hs-CRP), and pancreatic stone protein (PSP) in children with sepsis. MATERIAL AND METHODS A total of 214 patients with sepsis during hospitalization were enrolled. Serum levels of PCT, hs-CRP, and PSP were measured on day 1 of hospitalization and the survival rates of children were recorded after a follow-up of 28 days. Pearson's correlation analysis was conducted to test the association of PCT, hs-CRP, and PSP with pediatric critical illness score (PCIS). Logistic regression models were used to analyze the risk factors contributing to patients' death. The AUC was used to determine the value of PCT, hs-CRP, and PSP in the prognosis of patients with sepsis. RESULTS The expression of PCT, hs-CRP, and PSP in the dying patients was higher than in the surviving patients (p<0.001). Pearson's correlation analysis showed that serum PCT, hs-CRP, and PSP levels were negatively correlated with PCIS (p<0.001). Multivariate logistic regression revealed that PCT, hs-CRP, and PSP were independent risk factors for the prognosis of patients with sepsis (p<0.001). ROC analysis showed the AUC values of PCT, hs-CRP, and PSP were 0.83 (95% CI, 0.77-0.88), 0.76 (95% CI, 0.70-0.82), and 0.73 (95% CI, 0.67-0.79), respectively. The combined AUC value of PCT, hs-CRP, and PSP, was 0.92 (95% CI, 0.87-0.95), which was significantly increased compared with PCT, hs-CRP, or PSP (p<0.001). CONCLUSIONS The combination of serum PCT, hs-CRP, and PSP represents a promising biomarker of risk, and is a useful clinical tool for risk stratification of children with sepsis.

Effect of soluble inducible costimulator level and its polymorphisms on age-related macular degeneration.

Age-related macular degeneration (AMD) is the leading cause of blindness in the elderly population. Evidence has shown that the human immune system may play critical roles in this disease. Inducible costimulator (ICOS) promotes T-cell activation, differentiation, and T:B-cell interactions. The aim of the study was to understand the effect of ICOS on the development of AMD from genetic polymorphism perspective and serum level perspective. Two ICOS polymorphisms, rs10183087A/C and rs10932037C/T, were tested in 223 AMD cases and 262 healthy controls. The serum level of soluble ICOS (sICOS) was compared among subjects with different genotypes, as well as between AMD patients and controls. Data showed that prevalence of rs10183087CC genotype was significantly increased in AMD than in controls (p=0.001). Function analysis revealed that subjects carrying rs10183087CC genotype had higher serum levels of sICOS than those with AA or AC genotypes (p<0.05). When we compared serum levels of sICOS between cases and controls, results showed that AMD patients had significantly increased sICOS levels than healthy donors (p<0.05). Also, wet type cases were observed to have higher sICOS levels than cases with dry type (p<0.05). These data suggested ICOS polymorphism could affect the susceptibility to AMD by elevating protein expression, and serum levels of sICOS may be closed correlated with the development and progression of this disease.

Transforming growth factor-ß1 level in tears and corneal haze formation following flap-on or flap-off epi-LASIK.

OBJECTIVE: To observe the influence of flap-on or flap-off Epipolis laser in situ keratomileusis (epi-LASIK) on the release of transforming growth factor-ß1 (TGF-ß1) in tear fluid and corneal haze formation. METHODS: Thirty patients (60 eyes) with myopia underwent epi-LASIK surgery with epithelial flap repositioning (flap-on) in the right eyes and epithelial flap removal (flap-off) in the left eyes. The level of TGF-ß1 in tears was measured preoperatively and on days 1, 3, and 7 postoperatively. Corneal haze was graded at 1, 3 and 6 months after surgery. RESULTS: The mean preoperative spherical equivalent refraction was -4.98∓2.28 D (-2.50 to -7.25 D) in flap-on group and -5.20∓4.02 D (-1.75 to -7.00 D) in flap-off group, showing no significant difference between the two groups (P=0.80). TGF-ß1 levels in the tear fluid were similar in the two groups preoperatively (P=0.11) and at 1, 3, and 7 days postoperatively (P=0.55, 0.45, 0.19, respectively). TGF-ß1 levels in tears gradually decreased after the first postoperative day in both groups, but were still higher than the preoperative value till the 7th postoperative day. Corneal haze scores in the two groups were similar at 1 month (P=0.98), 3 months (P=0.52), and 6 months (P=0.72) after the operation. CONCLUSION: Flap-on and flap-off epi-LASIK surgeries do not differ significantly in postoperative TGF-ß1 levels in the tear fluid or in the postoperative haze scores. TGF-ß1 may play a role in corneal wound healing.

Effects of lysyl oxidase genetic variants on the susceptibility to rhegmatogenous retinal detachment and proliferative vitreoretinopathy.

Proliferative vitreoretinopathy (PVR), the most common cause of failure of rhegmatogenous retinal detachment (RD) surgery, is an anomalous scarring process related to ocular inflammation. Lysyl oxidase (LOX) is a copper-dependent amine oxidase that may play important roles in ocular tissue integrity. The aim of this study was to investigate whether polymorphisms in the LOX gene were associated with susceptibility to RD and PVR. We screened the promoter region of LOX gene and tested two previously reported polymorphisms (-22 G/C and 473 G/A) in RD patients with or without PVR and healthy controls. Data showed that prevalence of the -22CC genotype and -22C allele were significantly higher in the RD cases than in the control group after adjustment for sex and age (p < 0.001 and p < 0.001, respectively). Similarly, a significant difference was observed regarding LOX 473GA genotype and 473A allele between RD patients and healthy donors after adjustment for sex and age (p = 0.005 and p = 0.012, respectively). Also, when compared to RD cases without PVR, patients who developed PVR had significantly higher numbers of -22CC genotype and -22C allele (p = 0.048 and p = 0.003, respectively). These results indicated that LOX polymorphisms were associated with increased susceptibility to RD and PVR and suggest a potential correlation between LOX and ocular inflammation.

Tissue factor with age-related macular degeneration.

Wet age-related macular degeneration which incidence increases year by year is a blinding eye disease, but current clinical methods of treatment on this disease are limited and the outcome is not ideal. Recent studies have found abnormally high expression of tissue factors which are targets for the treatment of wet age-related macular degeneration to achieve a certain effect in the choroidal neovascularization. Related literatures are reviewed as following.

Primary vitrectomy for rhegmatogenous retinal detachment: an analysis of 512 cases.

BACKGROUND: Primary pars plana vitrectomy (PPPV) has gained widespread popularity in the treatment of rhegmatogenous retinal detachments (RRD). However, the surgical procedure is still flawed by a significant rate of anatomical and functional failures. The study was conducted to analyse the risk factors for a dissatisfying postoperative outcome. METHODS: We carried out a retrospective study of 512 cases of PPPV with a minimum follow-up of 3 months from one institution over a 9-year period. Preoperatively, 24.8% of patients (127 out of 512) were pseudophakic, 16.4% (84 out of 512) highly myopic, 19.9% (102 out of 512) had preoperative proliferative vitreoretinopathy (PVR) and 14.6% (75 out of 512) had vitreous haemorrhage. RESULTS: The follow-up period ranged from 3 to 108 months (median 14.8). Retinal reattachment was achieved with one operation in 70.7% (362 out of 512) and after one or more operations in 97.5% of cases (499 out of 512). The major reasons for redetachments were new retinal breaks, followed by a combination of new breaks and PVR, and PVR without apparent breaks. Postoperative visual acuities of > or =0.1 and > or =0.4 were achieved in 82.8% (424 out of 512) and 48.2% (247 out of 512) respectively. Out of 376 phakic patients at study entry, 66.4% (250 out of 376) underwent cataract surgery either in combination with PPPV or during the postoperative course. Factors that were significantly associated with either anatomical or functional failure included duration of symptoms, low preoperative visual acuity, myopia, amblyopia, hypotony, macular detachment, preoperative PVR, extent of detachment, involvement of inferior quadrants, no detectable breaks, large breaks, breaks posterior to the equator, surgeon, level of surgical training, endocryotherapy, and combined scleral buckling surgery. CONCLUSION: Primary pars plana vitrectomy is still flawed by a relatively high primary redetachment rate following the initial procedure. The advantages of the technique are a high final reattachment rate and relatively good functional results in a subset of patients with more complicated types of RRD. The risk factors for postoperative failures following PPPV for RRD match to a large extent those following scleral buckling surgery (SBS). Future improvements of the technique will have to focus on modifiable risk factors, such as details of the surgical procedures, surgical training and case selection, to distinguish it from SBS.