Clinical observation of bio-amnion implantation used in combined trabeculectomy for refractory glaucoma

AIM: To observe the clinical effect of bio-amnion implantation used in combined trabeculectomy for refractory glaucoma METHODS: Totally 86 eyes of 80 glaucoma patients were randomly divided into 2 groups. In experimental group, 43 eyes underwent trabeculectomy combined with bio-amnion implantation. In control group, 43 eyes only underwent trabeculectomy combined. The intraocular pressure(IOP), filtrative bleb and complications were observed. RESULTS: Following-up for 12 months, IOP: there was significant difference between the average IOP(15.5±1.1mmHg)in experimental group and the average IOP(19.7±2.5mmHg)in control group(P<0.05). Filtrative bleb: the incidence of the functional filtering bleb(86%)in experimental group was more than the one in control group(67%), there was significant different between the two groups(P<0.05). The incidence of complications of post-operation(shallow anterior chamber, choroidal detachment and bleb leaking)was lower than the one of the control group obviously. CONCLUSION: Combined trabeculectomy with bio-amnion implantation can increase the rate of success and reduce the incidence of complications

New Perspectives on Host-Parasite Interplay by Comparative Transcriptomic and Proteomic Analyses of Schistosoma japonicum

Schistosomiasis remains a serious public health problem with an estimated 200 million people infected in 76 countries. Here we isolated ~ 8,400 potential protein-encoding cDNA contigs from Schistosoma japonicum after sequencing circa 84,000 expressed sequence tags. In tandem, we undertook a high-throughput proteomics approach to characterize the protein expression profiles of a number of developmental stages (cercariae, hepatic schistosomula, female and male adults, eggs, and miracidia) and tissues at the host-parasite interface (eggshell and tegument) by interrogating the protein database deduced from the contigs. Comparative analysis of these transcriptomic and proteomic data, the latter including 3,260 proteins with putative identities, revealed differential expression of genes among the various developmental stages and sexes of S. japonicum and localization of putative secretory and membrane antigens, enzymes, and other gene products on the adult tegument and eggshell, many of which displayed genetic polymorphisms. Numerous S. japonicum genes exhibited high levels of identity with those of their mammalian hosts, whereas many others appeared to be conserved only across the genus Schistosoma or Phylum Platyhelminthes. These findings are expected to provide new insights into the pathophysiology of schistosomiasis and for the development of improved interventions for disease control and will facilitate a more fundamental understanding of schistosome biology, evolution, and the host-parasite interplay

Safety profile of 0.0015% tafluprost eye drops in China: a post-marketing observational study

AIM: To investigate the treatment pattern and safety of tafluprost for glaucoma and ocular hypertension (OH) in clinical practice in China. METHODS: This post-marketing observational study included patients who received tafluprost to lower intraocular pressure (IOP) within 30d between September 2017 and March 2020 in 20 hospitals in China. Adverse drug reactions (ADRs) during tafluprost treatment and within 30d after the treatment were collected. RESULTS: A total of 2544 patients were included in this study, of them 58.5% (1488/2544) had primary open angle glaucoma (POAG), 21.9% (556/2544) had OH and 19.7% (500/2544) used tafluprost for other reasons. Of 359 ADRs occurred in 10.1% (258/2544) patients, and no serious adverse event occurred. The most common ADR was conjunctival hyperemia (128 ADRs in 124 patients, 4.9%). Totally 1670 participants (65.6%) combined tafluprost with carbonic anhydrase inhibitors (CAIs; 37.1%, 620/1670), sympathomimetics (33.5%, 559/1670), β-blockers (33.2%, 555/1670), other prostaglandin analogs (PGAs; 15.6%, 260/1670) and other eye drops (15.1%, 253/1670). The highest incidence of conjunctival hyperemia was noted in patients who received tafluprost in combination with other PGAs (23 ADRs in 23 patients, 8.8%, 23/260) and the lowest was in combination with CAIs (16 ADRs in 16 patients, 2.6%, 16/620). Tafluprost was applied in primary angle-closure glaucoma (41.6%, 208/500), after glaucoma surgery (17.8%, 89/500) and after non-glaucoma surgery (15.8%, 79/500). CONCLUSION: Tafluprost is safe for POAG and OH, and tolerable when combined with other eye drops and under various clinical circumstances

Comparative efficacy and safety of the fixed versus unfixed combination of latanoprost and timolol in Chinese patients with open-angle glaucoma or ocular hypertension

<p>Abstract</p> <p>Background</p> <p>A noninferiority trial was conducted to evaluate the efficacy of a single evening dose of fixed-combination latanoprost 50 μg/mL and timolol 0.5 mg/mL (Xalacom^®; LTFC), in Chinese patients with primary open-angle glaucoma (POAG) or ocular hypertension (OH) who were insufficiently controlled on β-blocker monotherapy or β-blocker-based dual therapy.</p> <p>Methods</p> <p>This 8-week, randomized, open-label, parallel-group, noninferiority study compared once-daily evening dosing of LTFC with the unfixed combination of latanoprost, one drop in the evening, and timolol, one drop in the morning (LTuFC). The primary efficacy endpoint was the mean change from baseline to week 8 in diurnal intraocular pressure (IOP; mean of 8 AM, 10 AM, 2 PM, 4 PM IOPs). LTFC was considered noninferior to LTuFC if the upper limit of the 95% confidence interval (CI) of the difference was < 1.5 mmHg (analysis of covariance).</p> <p>Results</p> <p>Baseline characteristics were similar for LTFC (N = 125; POAG, 70%; mean IOP, 25.8 mmHg) and LTuFC (N = 125; POAG, 69%; mean IOP, 26.0 mmHg). Mean diurnal IOP changes from baseline to week 8 were -8.6 mmHg with LTFC and -8.9 mmHg with LTuFC (between-treatment difference: 0.3 mmHg; 95%-CI, -0.3 to 1.0). Both treatments were well tolerated.</p> <p>Conclusions</p> <p>A single evening dose of LTFC was at least as effective as the unfixed combination of latanoprost in the PM and timolol in the AM in reducing IOP in Chinese subjects with POAG or OH whose IOP was insufficiently reduced with β-blocker monotherapy or β-blocker-based dual therapy. LTFC is an effective and well tolerated once-daily treatment for POAG and OH.</p> <p>Trial registration</p> <p>Clinicaltrials.gov registration: <a href="http://www.clinicaltrials.gov/ct2/show/NCT00219596">NCT00219596</a></p

Numerical simulation of slurry jets using mixture model

Slurry jets in a static uniform environment were simulated with a two-phase mixture model in which flow-particle interactions were considered. A standard k-ε turbulence model was chosen to close the governing equations. The computational results were in agreement with previous laboratory measurements. The characteristics of the two-phase flow field and the influences of hydraulic and geometric parameters on the distribution of the slurry jets were analyzed on the basis of the computational results. The calculated results reveal that if the initial velocity of the slurry jet is high, the jet spreads less in the radial direction. When the slurry jet is less influenced by the ambient fluid (when the Stokes number St is relatively large), the turbulent kinetic energy k and turbulent dissipation rate ε, which are relatively concentrated around the jet axis, decrease more rapidly after the slurry jet passes through the nozzle. For different values of St, the radial distributions of streamwise velocity and particle volume fraction are both self-similar and fit a Gaussian profile after the slurry jet fully develops. The decay rate of the particle velocity is lower than that of water velocity along the jet axis, and the axial distributions of the centerline particle streamwise velocity are self-similar along the jet axis. The pattern of particle dispersion depends on the Stokes number St. When St = 0.39, the particle dispersion along the radial direction is considerable, and the relative velocity is very low due to the low dynamic response time. When St = 3.08, the dispersion of particles along the radial direction is very little, and most of the particles have high relative velocities along the streamwise direction

High Glucose Represses hERG K+ Channel Expression through Trafficking Inhibition

Background/Aims: Abnormal QT prolongation is the most prominent cardiac electrical disturbance in patients with diabetes mellitus (DM). It is well known that the human ether-ago-go-related gene (hERG) controls the rapid delayed rectifier K+ current (IKr) in cardiac cells. The expression of the hERG channel is severely down-regulated in diabetic hearts, and this down-regulation is a critical contributor to the slowing of repolarization and QT prolongation. However, the intracellular mechanisms underlying the diabetes-induced hERG deficiency remain unknown. Methods: The expression of the hERG channel was assessed via western blot analysis, and the hERG current was detected with a patch-clamp technique. Results: The results of our study revealed that the expression of the hERG protein and the hERG current were substantially decreased in high-glucose-treated hERG-HEK cells. Moreover, we demonstrated that the high-glucose-mediated damage to the hERG channel depended on the down-regulation of protein levels but not the alteration of channel kinetics. These discoveries indicated that high glucose likely disrupted hERG channel trafficking. From the western blot and immunoprecipitation analyses, we found that high glucose induced trafficking inhibition through an effect on the expression of Hsp90 and its interaction with hERG. Furthermore, the high-glucose-induced inhibition of hERG channel trafficking could activate the unfolded protein response (UPR) by up-regulating the expression levels of activating transcription factor-6 (ATF-6) and the ER chaperone protein calnexin. In addition, we demonstrated that 100 nM insulin up-regulated the expression of the hERG channel and rescued the hERG channel repression caused by high glucose. Conclusion: The results of our study provide the first evidence of a high-glucose-induced hERG channel deficiency resulting from the inhibition of channel trafficking. Furthermore, insulin promotes the expression of the hERG channel and ameliorates the high-glucose-induced inhibition of the hERG channel

Neurogenin 2 Converts Mesenchymal Stem Cells into a Neural Precursor Fate and Improves Functional Recovery after Experimental Stroke

Background: Neurogenin2 (Ngn2) is a proneural gene that directs neuronal differentiation of progenitor cells during development. Here, we investigated whether Ngn2 can reprogram MSCs to adopt a neural precursor fate and enhance the therapeutic effects of MSCs after experimental stroke. Methods: In vitro, MSCs were transfected with lenti-GFP or lenti-Ngn2. Following neuronal induction, cells were identified by immunocytochemistry, Western blot and electrophysiological analyses. In a stroke model induced by transient right middle cerebral artery occlusion (MCAO), PBS, GFP-MSCs or Ngn2-MSCs were injected 1 day after MCAO. Behavioral tests, neurological and immunohistochemical assessments were performed. Results: In vitro, Ngn2-MSCs expressed neural stem cells markers (Pax6 and nestin) and lost the potential to differentiate into mesodermal cell types. Following neural induction, Ngn2-MSCs expressed higher levels of neuron-specific proteins MAP2, Tuj1 and NeuN, and also expressed voltage-gated Na+ channel, which was absent in GFP-MSCs. In vivo, after transplantation, Ngn2-MSCs significantly reduced apoptotic cells, decreased infarct volume, and increased the expression of VEGF and BDNF. Finally, Ngn2-MSCs treated animals showed the highest functional recovery among the three groups. Conclusions: Ngn2 was sufficient to convert MSCs into a neural precursor fate and transplantation of Ngn2-MSCs was advantageous for the treatment of stroke rats