Efficacy and safety of iodized lecithin tablets versus spironolactone in alleviating central serous retinopathy among Chinese patients with uncontrolled diabetes.

To compare the effectiveness and safety of spironolactone versus lecithin-bound iodine in patients with central serous retinopathy (CSR). Chinese diabetes patients aged>18 years with CSR with persistent increased level of subretinal fluid (SRF) were enrolled. Subjects were randomized to receive either oral lecithin-bound iodine (390µg/kg/day) or oral spironolactone (50mg/day) for 6 months. A total of 200 patients were randomized and completed the study. Compared to spironolactone group, patients treated with lecithin-bound iodine had greater proportion of eye with complete resolution (87% vs 81%, p>0.005). Higher improvement in height of SRF was observed in lecithin-bound iodine-treated patients as compared with Spironolactone-treated patients (91.2[87.5] vs 142.5 [121.1]; p>0.005). However, no statistically significant difference was observed on none of comparisons. Compared to Spironolactone, the patients treated with lecithin-bound iodine had greater improvement in lesion size, central macular thickness and best-corrected visual acuity. However, no statistically significant difference was observed in any of parameter assessed. (p>0.005). The results of the present study suggested that the lecithin-bound iodine was found more effective (nnumerically) than spironolactone in Chinese diabetes patients with CSR.

LY294002 attenuates inflammatory response in endotoxin-induced uveitis by downregulating JAK3 and inactivating the PI3K/Akt signaling.

CONTEXT: Uveitis is a prevalent inflammatory eye disease that damages the vision of patients and even leads to blindness. LY294002, an inhibitor of PI3K, was reported to suppress the inflammation and alleviate the progression of many diseases. However, the function of LY294002 in uveitis is unclear. OBJECTIVE: This study aimed to explore the function of LY294002 in endotoxin-induced uveitis (EIU). MATERIALS AND METHODS: EIU rat models were established via a single intravitreal injection of LPS. At 24 h after LPS injection, the rats received LY294002 treatment for 14 days. The histopathology was observed by H&E staining. The concentration of proinflammatory cytokines in aqueous humor was tested by ELISA. The expression of proinflammatory cytokines in the iris ciliary body (ICB) and retina of EIU rats were detected by RT-qPCR. JAK3, PI3K, and Akt expression were assessed by RT-qPCR and western blotting. Translocation of Akt in rat retinal Müller cells (rMC-1) was evaluated by immunofluorescence staining. RESULTS: LY294002 alleviated ocular inflammation and decreased inflammatory cell infiltration in the anterior chamber, iris, ciliary body, vitreous cavity, and retina of EIU rats. LY294002 decreased the concentration of proinflammatory cytokines INF-γ, IL-17, IL-6, TNF-α, and IL-1ß in aqueous humor and their expression in the ICB and retina of EIU rats. LY294002 downregulated JAK3 expression in EIU rats. LY294002 inhibited p-PI3K and p-Akt expression in EIU rats and restrained Akt translocation from cytoplasm to cell membrane in LPS-treated rMC-1 cells. CONCLUSION: LY294002 ameliorates inflammation in EIU by downregulating JAK3 and inactivating the PI3K/Akt signaling.

Associations of the PON1 rs662 polymorphism with circulating oxidized low-density lipoprotein and lipid levels: a systematic review and meta-analysis.

BACKGROUND: Several meta-analyses have demonstrated that the rs662 polymorphism in Paraoxonase 1 gene (PON1) gene is associated with coronary heart disease (CHD). However, it is still uncertain whether this polymorphism is associated with the plasma levels of oxidized low-density lipoprotein (Ox-LDL) and lipids. This meta-analysis is aimed to clarify the relationships between the rs662 polymorphism and plasma levels of Ox-LDL and lipids. METHODS: By searching in PubMed, Google Scholar, Web of Science, Cochrane Library, Wanfang, VIP and CNKI databases, 5 studies (1369 subjects) and 85 studies (46,740 subjects) were respectively identified for Ox-LDL association analysis and lipid association analysis. Standardized mean difference (SMD) was used to estimate the effects of the rs662 polymorphism on plasma Ox-LDL and lipid levels. RESULTS: The carriers of the variant R allele had higher levels of Ox-LDL (SMD = 0.23, 95% CI = 0.10-0.36, P <  0.01), triglyceride (TG) (SMD = 0.06, 95% CI = 0.01-0.11, P = 0.02), total cholesterol (TC) (SMD = 0.04, 95% CI = 0.00-0.07, P = 0.05) and low-density lipoprotein cholesterol (LDL-C) (SMD = 0.04, 95% CI = 0.00-0.08, P = 0.04) than the non-carriers. CONCLUSIONS: This meta-analysis suggests that the association between the PON1 rs662 polymorphism and CHD may partly be mediated by abnormal Ox-LDL and lipid levels caused by the R allele.

Effectiveness of Neuromuscular Electrical Stimulation on Patients With Dysphagia With Medullary Infarction.

OBJECTIVE: To evaluate and compare the effects of neuromuscular electrical stimulation (NMES) acting on the sensory input or motor muscle in treating patients with dysphagia with medullary infarction. DESIGN: Prospective randomized controlled study. SETTING: Department of physical medicine and rehabilitation. PARTICIPANTS: Patients with dysphagia with medullary infarction (N=82). INTERVENTIONS: Participants were randomized over 3 intervention groups: traditional swallowing therapy, sensory approach combined with traditional swallowing therapy, and motor approach combined with traditional swallowing therapy. Electrical stimulation sessions were for 20 minutes, twice a day, for 5d/wk, over a 4-week period. MAIN OUTCOME MEASURES: Swallowing function was evaluated by the water swallow test and Standardized Swallowing Assessment, oral intake was evaluated by the Functional Oral Intake Scale, quality of life was evaluated by the Swallowing-Related Quality of Life (SWAL-QOL) Scale, and cognition was evaluated by the Mini-Mental State Examination (MMSE). RESULTS: There were no statistically significant differences between the groups in age, sex, duration, MMSE score, or severity of the swallowing disorder (P>.05). All groups showed improved swallowing function (P≤.01); the sensory approach combined with traditional swallowing therapy group showed significantly greater improvement than the other 2 groups, and the motor approach combined with traditional swallowing therapy group showed greater improvement than the traditional swallowing therapy group (P<.05). SWAL-QOL Scale scores increased more significantly in the sensory approach combined with traditional swallowing therapy and motor approach combined with traditional swallowing therapy groups than in the traditional swallowing therapy group, and the sensory approach combined with traditional swallowing therapy and motor approach combined with traditional swallowing therapy groups showed statistically significant differences (P=.04). CONCLUSIONS: NMES that targets either sensory input or motor muscle coupled with traditional therapy is conducive to recovery from dysphagia and improves quality of life for patients with dysphagia with medullary infarction. A sensory approach appears to be better than a motor approach.

Prognostic value of preoperative right ventricular geometry and tricuspid valve tethering area in patients undergoing tricuspid annuloplasty.

BACKGROUND: Patients who undergo tricuspid annuloplasty during left-side heart valve surgery have a poor postoperative clinical outcome. However, preoperative right ventricular (RV) echocardiography parameters that predict adverse events in these patients are poorly understood. METHODS AND RESULTS: We studied 74 patients (age, 58±10 years; men, 27%) with significant tricuspid regurgitation who consequently underwent tricuspid annuloplasty during left-side heart valve surgery. A total of 26 adverse events (22 heart failures and 4 cardiovascular deaths) occurred during a median follow-up of 26 months. RV midcavity diameter (hazard ratio=2.44; 95% confidence interval=1.48-4.02; P<0.01), RV longitudinal dimension (hazard ratio=1.64; 95% confidence interval=1.10-2.45; P=0.02), and tricuspid valve tethering area (hazard ratio=3.25; 95% confidence interval=1.71-6.19; P<0.01) were independently associated with adverse events after adjustment for age and New York Heart Association class III/IV. Receiver-operator characteristic curve analysis demonstrated that RV midcavity diameter (area under the curve=0.74; P<0.01) and tricuspid valve tethering area (area under the curve=0.70; P=0.04) were most associated with adverse events at the 1-year follow-up. The presence of either a large RV midcavity diameter or tricuspid valve tethering area was predictive of adverse outcome at 1 year after tricuspid annuloplasty. CONCLUSIONS: The present study demonstrates that RV geometry dimensions, namely RV midcavity diameter and tricuspid valve tethering area, are important preoperative measures associated with adverse events in patients undergoing tricuspid annuloplasty.

Improved LASSO priors for shrinkage quantitative trait loci mapping.

Recently, the Bayesian least absolute shrinkage and selection operator (LASSO) has been successfully applied to multiple quantitative trait loci (QTL) mapping, which assigns the double-exponential prior and the Student's t prior to QTL effect that lead to the shrinkage estimate of QTL effect. However, as reported by many researchers, the Bayesian LASSO usually cannot effectively shrink the effects of zero-effect QTL very close to zero. In this study, the double-exponential prior and Student's t prior are modified so that the estimate of the effect for zero-effect QTL can be effectively shrunk toward zero. It is also found that the Student's t prior is virtually the same as the Jeffreys' prior, since both the shape and scale parameters of the scaled inverse Chi-square prior involved in the Student's t prior are estimated very close to zero. Besides the two modified Bayesian Markov chain Monte Carlo (MCMC) algorithms, an expectation-maximization (EM) algorithm with use of the modified double-exponential prior is also adapted. The results shows that the three new methods perform similarly on true positive rate and false positive rate for QTL detection, and all of them outperform the Bayesian LASSO.

Purification of a protein from coelomic fluid of the earthworm Eisenia foetida and evaluation of its hemolytic, antibacterial, and antitumor activities.

CONTEXT: Earthworm Eisenia foetida (Lumbricus rubellus), a traditional Chinese medicine, is used for treating many diseases, and its coelomic fluid has extensive biological functions. OBJECTIVE: The hemolytic, antibacterial and antitumor activities of an earthworm protein purified from coelomic fluid were investigated in vitro. MATERIALS AND METHODS: We used ultrafiltration, gel chromatography, and ion exchange chromatography in sequence to isolate and purify an earthworm protein from coelomic fluid (ECFP), and ECFP was characterized by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE). Hemolytic assay and antibacterial tests were applied to determine the cytolytic activity of ECFP. The MTT method was carried out to evaluate the antitumor effect of ECFP on HeLa cells and LTEP-A2 cells. RESULTS: ECFP, with molecular weight determined to be approximately 38.6 kilodaltons (KDa), was shown to possess significant hemolytic activity to chicken red blood cells (CRBC) (minimal hemolytic concentration 0.39 µg/mL). Antibacterial effect of ECFP obviously tested against Escherichia coli (minimal bactericidal concentration, MBC 180 µg/ mL) and Staphylococcus aureus (MBC 90 µg/mL) were observed. Moreover, ECFP notably inhibited the proliferation of HeLa cells (IC50 77 µg/mL) and LTEP-A2 cells (IC50 126 µg/mL) both in a time- and dose-dependent manner. DISCUSSION AND CONCLUSION: ECFP could serve as a component of the innate defense system of earthworms against foreign organisms, and thus it has potential pharmaceutical application in the future.

[Effects of shear stress on expression of plasminogen activator (tPA and uPA) in cultured kidney proximal tubular epithelial cells and its significance].

In this study, we assessed the effects of shear stress on the expression of plasminogen activator(tPA and uPA) mRNA in cultured NRK-52E cells (a kidney proximal tubular epithelial cell line of normal rat origin) and investigated the mechanism of tubulointerstitial extracellular matrix (ECM) remodeling in the early stage of diabetic nephropathy (DN). The cultured NRK-52E cells were exposed to shear stress of 5 and 10 dyn/cm2 for 1, 3 and 6 hours respectively. Semi-quantity RT-PCR was used to detect the expression of tPA and uPA mRNA. Shear stress down-regulated the expression of tPA and uPA mRNA in cultured NRK-52E cells in a magnitude and time-dependent way. The results suggested that the increased tubular shear stress in the early-stage of DN could decrease the expression of tPA and uPA in renal proximal tubular cells, lead to the reduction of tubulointerstitial fibrinolytic activity and involve in the remodeling of ECM.

[Effects of losartan on expressions of plasminogen activator and plasminogen activator inhibitor-1 of rat proximal tubular epithelial cells cultured with high glucose].

OBJECTIVE: To investigate the effects of high glucose on expressions of plasminogen activator (PA) and plasminogen activator inhibitor-1 (PAI-1) of rat proximal tubular epithelial cells, and the role of angiotensin II receptor antagonist Losartan. METHODS: The cultured NRK-52E cells (a renal proximal tubular epithelial cell line of rat origin) were divided into five groups: control group, mannitol group (5 mmol/L D-glucose plus 25 mmol/L mannitol), high glucose group (30 mmol/L D-glucose), losartan group (10(-3) mmol/L losartan), high glucose plus losartan group (30 mmol/L D-glucose plus 10(-3) mmol/L losartan). Semi-quantity RT-PCR was used to detect the expression of PA/PAI-1 mRNA. RESULTS: Compared with control group, the high glucose group decreased the expressions of tissue plasminogen activator (tPA) and urokinase plasminogen activator (uPA) mRNAs (P < 0.01) and increased PAI-1 mRNA expression (P < 0.01) in cultured NRK-52E cells. Losartan could reverse partly the expression of PA/PAI-1 mRNA. Compared to high glucose group, the PA mRNA expression was significantly increased (P < 0.01) and the PAI-1 mRNA expression was decreased greatly (P < 0.01) to high glucose plus losartan group. CONCLUSION: The abnormal expression of PA/PAI-1 mRNA may play an important role in the accumulation of extracellular matrix (ECM) of diabetic nephropathy (DN). Losartan may keep the balance of PA/PAI-1 and have a protective effect on DN.

Bayesian analysis of genetic architecture of quantitative trait using data of crosses of multiple inbred lines.

Using the data of crosses of multiple of inbred lines for mapping QTL can increase QTL detecting power compared with only cross of two inbred lines. Although many fixed-effect model methods have been proposed to analyze such data, they are largely based on one-QTL model or main effect model, and the interaction effects between QTL are always neglected. However, effectively separating the interaction effects from the residual error can increase the statistical power. In this article, we both extended the novel Bayesian model selection method and Bayesian shrinkage estimation approaches to multiple inbred line crosses. With two extensions, interacting QTL are effectively detected with high solution; in addition, the posterior variances for both main effects and interaction effects are also subjected to full Bayesian estimate, which is more optimal than two step approach involved in maximum-likelihood. A series of simulation experiments have been conducted to demonstrate the performance of the methods. The computer program written in FORTRAN language is freely available on request.