Recanalization of Xen45 gel stent implant occlusion using 10 - 0 nylon suture in refractory glaucoma: a case report.

BACKGROUND: Xen Gel Stent implant is a new minimally invasive surgical treatment for glaucoma that has been proven effectiveness and safety profile. However, it may also lead to some complications. Xen Gel Stent occlusion is a relatively rare complication reported less frequently and has limited treatment experience. In our case report, we proposed a novel surgical treatment using a 10 - 0 nylon suture to successfully recanalize the occluded Xen45 Gel Stent. CASE PRESENTATION: A 16-year-old female patient had bilateral juvenile glaucoma for the past 5 years. Her right eye had undergone three glaucoma surgeries but failed. At a presentation to our hospital, the right eye's intraocular pressure (IOP) was 30 mmHg despite applying four different active principles. Xen45 Gel Stent implant was chosen for treatment, but six days after implantation, the IOP rose to 40 mmHg as a result of an anterior chamber tip occlusion of the Xen45 Gel Stent. Nd: YAG laser shockwave therapy was attempted but failed. The patient eventually had to return to the operating room for a revision procedure. The Xen45 Gel Stent was recanalized from the ab externo by making an L-shaped conjunctival incision at the fornix base and threading a 10 - 0 nylon suture through it. The IOP was successfully controlled in the 11-month follow-up without medication. CONCLUSION: If postoperative occlusion arises after Xen45 Gel Stent implantation, surgery using 10 - 0 nylon suture to recanalize Xen45 Gel Stent should be considered as a relatively safe, effective that does not require removal of Xen45 Gel Stent.

Efficacy of Lenvatinib, a multitargeted tyrosine kinase inhibitor, on laser-induced CNV mouse model of neovascular AMD.

Neovascular age-related macular degeneration (AMD) is a leading cause of vision loss worldwide. Although intravitreal injection of anti-VEGF antibodies and VEGF Trap have significant clinical benefits, the complications of intravitreal injection, drug resistance and patient compliance still need to be concerned. In this study, the effects of an orally administered multi-targeted tyrosine kinase inhibitor (Lenvatinib, E7080) were evaluated in vitro and in vivo on neovascular AMD mouse model. The results showed that E7080 effectively inhibited the proliferation, migration and tubule formation of human choroidal microvascular endothelial cells (HCMECs), and suppressed the angiogenesis of zebrafish subintestinal vessels without causing malformation. The anti-angiogenic effect of E7080 on the laser-induced choroidal neovascularization (CNV) mouse model by oral administration of 10 mg/kg/day was observed. The fluorescein angiography showed CNV leakage area in treatment group vs control group was 3.407 ±â€¯0.2939 vs 5.202 ±â€¯0.9001 (P = .0133) at day 7th post laser-induced CNV, 1.138 ±â€¯0.4334 vs 3.122 ±â€¯0.3466 (P = .0064) at day 14th, 1.401 ±â€¯0.6577 vs 2.781 ±â€¯0.9815 (P = .00262) at day 21th respectively. Moreover, pharmacokinetics analysis in rat retina showed that E7080 rapidly penetrated the blood-retina barrier to retina through oral administration. The T1/2 in retina was 3.81 ±â€¯0.77 h, the Tmax was 4.60 ±â€¯0.73 h, the AUC0-∞ was 110448.51 ± 18532.51 h*ng/g after a single dose administration analyzed by liquid chromatography-tandem mass spectrometry (LC/MS/MS). In conclusion, our study suggested that orally administered E7080 can be a novel therapeutic strategy for neovascular AMD.

Modified superior bleb needling of rare hypertrophic bleb after trabeculectomy: A case series.

BACKGROUND: Hypertrophic bleb is a rare complication of glaucoma filtration surgery characterized by an elevated bleb extended through the nasal 180 degrees of the eye and usually with a normal IOP. Currently, there is little experience and no existing standardized treatment. We describe a new method called modified superior bleb needling and evaluate the clinical outcomes in affected eyes. METHODS: In this retrospective, consecutive interventional case series, patients who developed hypertrophic blebs after trabeculectomy from November 2015 to August 2020 at West China Hospital were enrolled. We innovatively adopted a modified superior bleb needling to allow aqueous humor to outflow into the superior subconjunctival space. Repeat needlings were performed if necessary. The technical and clinical success rate and complications were reported. RESULTS: At the time of the last follow-up, complete success was achieved in 8/10 patients, qualified success was achieved in 9/10 patients, and failure was achieved in 1/10 patients. Eight patients had a low filtering bleb and IOP ≤21 mmHg. There was no statistically significant difference between the preneedling and postneedling IOP (p > 0.05). CONCLUSION: Modified superior bleb needling is effective for hypertrophic blebs after trabeculectomy, and there was no significant impact on anterior chamber depth or IOP, making it a viable or preferred alternative option. It is worthy of further study and wider usage.

NOD2/CARD15 gene mutation identified in a Chinese family with Blau syndrome.

PURPOSE: To characterize the clinical features of a Chinese pedigree with Blau syndrome and to identify mutations in the NOD2/CARD15 (nucleotide-binding oligomerization domain containing 2/caspase recruitment domain family, member 15) gene. METHODS: Clinical features of this family were evaluated. Genomic DNA was obtained from blood samples, and all exons of NOD2/CARD15 were amplified by polymerase chain reaction (PCR) and direct DNA sequencing of PCR products was performed for mutations in NOD2/CARD15. RESULTS: Granulomatous arthritis, uveitis, and skin granulomas were found in all affected members. Sequencing analysis demonstrated a heterozygous C>T mutation in exon 4 of NOD2/CARD15 in all patients of this pedigree, which resulted in an amino acid substitution at position 334 (p.R334W). CONCLUSIONS: The R334W mutation in NOD2/CARD15 caused Blau syndrome in a Chinese pedigree. This is the first report of R334W mutation in NOD2/CARD15 in a Chinese pedigree of this disease.

Review of various NAMPT inhibitors for the treatment of cancer.

Nicotinamide phosphoribosyltransferase (NAMPT) is a rate-limiting enzyme in the NAD salvage pathway of mammalian cells and is overexpressed in numerous types of cancers. These include breast cancer, ovarian cancer, prostate cancer, gastric cancer, colorectal cancer, glioma, and b-cell lymphoma. NAMPT is also known to impact the NAD and NADPH pool. Research has demonstrated that NAMPT can be inhibited. NAMPT inhibitors are diverse anticancer medicines with significant anti-tumor efficacy in ex vivo tumor models. A few notable NAMPT specific inhibitors which have been produced include FK866, CHS828, and OT-82. Despite encouraging preclinical evidence of the potential utility of NAMPT inhibitors in cancer models, early clinical trials have yielded only modest results, necessitating the adaptation of additional tactics to boost efficacy. This paper examines a number of cancer treatment methods which target NAMPT, including the usage of individual inhibitors, pharmacological combinations, dual inhibitors, and ADCs, all of which have demonstrated promising experimental or clinical results. We intend to contribute further ideas regarding the usage and development of NAMPT inhibitors in clinical therapy to advance the field of research on this intriguing target.

Growth Kinetics of Bacillus pasteurii in Solid-Free Drilling Fluids.

A broken stratum is a complex stratum often encountered during drilling. Under erosion of the drilling fluid and disturbance of the drill pipe string, the rock in the well wall of the broken stratum is prone to collapsing and falling off, causing the well wall to lose its stability. Improving the cementing force between the broken blocks and forming a complete well wall are essential for overcoming this instability. The present study combined microbially induced calcite precipitation technology with solid-free drilling fluid technology for the first time to formulate a drilling fluid to overcome the instability of the well wall of a broken stratum. However, first and foremost, the growth of microorganisms in drilling fluids must be elucidated. To this end, experimental and theoretical analyses were performed to examine Bacillus pasteurii growth in drilling fluids composed of a single agent or combinations of various materials, such as a zwitterionic coating agent (FA367), a biopolymer (XC), a polyacrylate polymer (PAC-LV), and potassium polyacrylate (K-PAM). Experimental B. pasteurii growth data were then fitted using a modified Gompertz model. The mean square error indicated that the generated model had a reasonable degree of fit, and the bias and accuracy factors showed that the model could predict B. pasteurii growth. Among the different drilling fluid combinations used, suitable fluids for B. pasteurii growth were XC alone, XC, and PAC-LV in the two-material-based fluid and FA367, XC, and K-PAM in the three-material-based fluid. These results provide a solid foundation for the development of microbial drilling fluids to solve instability problems in broken geological formations.

Design, synthesis and biological evaluation of a novel tubulin inhibitor 7a3 targeting the colchicine binding site.

Tubulin inhibitors that target the colchicine binding site continue to emerge as promising anticancer agents. In this study, based on the anti-proliferative activities, a novel tubulin inhibitor 7a3 targeting the colchicine binding site was designed, synthesized, and optimized from a series of novel cis-restricted pyrazole analogues of combretastatin A-4. The structure-activity relationships (SARs) of these newly synthesized compounds are summarized indicating that the methyl substituent at the N1 position and deamination were significantly important for the anti-proliferative efficacy. The optimized compound 7a3 exhibited the ability to arrest the cell cycle in the G2/M phase, induce cell apoptosis, and inhibit cell migration in tumour cells. The results of the immunofluorescence analysis using confocal microscopy and the tubulin polymerization assay revealed that tubulin assembly was disrupted by 7a3 in vitro. Furthermore, the targeting identification of 7a3 was illuminated by solving the crystal structure of 7a3 in complex with tubulin at a resolution of 3.2 Š(PDB code 5Z4U), which confirmed the result of molecular docking and further demonstrated that 7a3 binds to the site of colchicine. Moreover, the pharmacokinetic analysis in mouse plasma showed that 7a3 rapidly reached a peak concentration at 0.25 h after intraperitoneal administration, and the T1/2, Cmax, and AUC0-inf were 1.67 ±â€¯0.28 h, 882 ±â€¯71 ng mL-1, and 1166 ±â€¯129 h ng·mL-1, respectively, after a single-dose administration analysed by liquid chromatography-tandem mass spectrometry (LC/MS/MS). In addition, the in vivo study indicated that 7a3 significantly inhibited the tumour growth of the SK-OV-3 xenograft in a nude mouse model. In conclusion, our study proved 7a3 to be a potential microtubule-targeting drug for cancer therapy. The SARs and mechanism of action studies of 7a3 based on the X-ray co-crystal structure provided insights into the next-generation tubulin inhibitors for cancer therapy.

Antiviral Activity of a Cloned Peptide RC28 Isolated from the Higher Basidiomycetes Mushroom Rozites caperata in a Mouse Model of HSV-1 Keratitis.

An Escherichia coli-expressed peptide with a molecular weight of 28.26, derived from the complementary DNA of antiviral protein RC28 isolated from the mushroom Rozites caperata (=Cortinarius caperatus), demonstrated potent antiviral activity against herpes simplex virus-1 in Vero cells and in a herpes simplex virus-1 mouse keratitis model. Plaque assays in Vero cells showed that the peptide reduced viral yields by at least 1.2 logs; in the animal model the cloned peptide delayed the occurrence of stromal keratitis and alleviated the severity of the disease. We believe this is the first report of a cloned mushroom peptide with antiviral activity for the prevention and treatment of a viral disease.

A case hypersensitive to bimatoprost and dexamethasone.

PURPOSE: The purpose of this study was to report a case hypersensitive to topical bimatoprost and dexamethasone, but with no responsiveness to both latanoprost and travoprost. CASE: A 41-year-old Chinese female presented with unilateral glaucoma secondary to iridocyclitis and long-term use of topical steroid. Trabeculectomy only worked for 9 months and then additional topical glaucoma medications were required to control the intraocular pressure (IOP). All commonly used IOP-lowering medications failed, except for bimatoprost, which significantly lowered the IOP. Topical dexamethasone increased IOP and caused ocular hypertension. Ultrasound biomicroscopy (UBM) was used to evaluate the anterior segment of the affected eye. Genomic DNA was extracted for sequence analysis of gene of prostaglandin F receptor (FP), E receptor 1 (EP1) and 2 (EP2) and myocilin. RESULTS: UBM revealed cyclodialysis in the patient's affected eye after a single dosage of bimatoprost. The cyclodialysis resolved when IOP was elevated with the topical use of dexamethasone. The dexamethasone-induced high IOP could only be controlled by bimatoprost, whereas the bimatoprost-induced low IOP could only be elevated by topical dexamethasone. Allele C of rs3753380 and allele A of rs3766355 in FP gene and a -224T>C variation of myocilin gene were found in this patient. In addition, a novel heterozygous Cys346Tyr mutation was identified in EP2 gene. No sequence variation was found in EP1 gene. CONCLUSIONS: The hypersensitivity of the affected eye to topical bimatoprost may be a result, at least in part, of cyclodialysis. The sequence analysis results suggested that, besides the polymorphism of FP gene, there might be some other mechanisms underlying the irresponsiveness of this patient to both latanoprost and travoprost. The mechanisms underlying the bimatoprost-induced cyclodialysis might correlate with its receptor selectivity. The -224T>C variation in the myocilin gene may affect the regulation of expression of this gene by dexamethasone.