Comparison of keratoplasty outcomes at the scar versus edema stages of keratoconus.

PURPOSE: To assess the outcomes of deep anterior lamellar keratoplasty or penetrating keratoplasty at the scar and the edema stages. METHODS: Forty-five patients (45 eyes) with keratoconus scar stage (scar group, n=26; penetrating keratoplasty a subgroup, n=7; deep anterior lamellar keratoplasty b subgroup, n=19) and keratoconus edema stage (edema group, n=19; penetrating keratoplasty c subgroup, n=12; deep anterior lamellar keratoplasty d group, n=7) who received penetrating keratoplasty or deep anterior lamellar keratoplasty from 2000 to 2022 were retrospectively studied. At 1, 6, and 12 months after surgery, the best-corrected visual acuity, astigmatism, spherical equivalent, corneal endothelial cell density, and complications were analyzed. RESULTS: The best-corrected visual acuity and average corneal endothelial cell loss rate were not significantly different between the scar and edema groups (p>0.05). At 6 and 12 months after surgery, the astigmatism and spherical equivalent in the scar group were significantly lower than those in the edema group (p<0.05). The spherical equivalent of the deep anterior lamellar keratoplasty b subgroup was lower than that of the penetrating keratoplasty a subgroup in the scar group 6 months after surgery (p<0.05). In the edema group, there was no significant difference in spherical equivalent between subgroups (p>0.05). There were no significant differences in best-corrected visual acuity and astigmatism between subgroups within the two groups (p>0.05). In comparison to the scar group, the edema group experienced more complications. According to a survival analysis, there was no statistically significant difference between the scar group and the edema group regarding the progression of vision. CONCLUSIONS: In terms of the outcomes and prognosis for vision after keratoplasty with edema stage and scar stage, deep anterior lamellar keratoplasty may be as effective as penetrating keratoplasty.

Identification of KRAS mutation-associated gut microbiota in colorectal cancer and construction of predictive machine learning model.

Gut microbiota has demonstrated an increasingly important role in the onset and development of colorectal cancer (CRC). Nonetheless, the association between gut microbiota and KRAS mutation in CRC remains enigmatic. We conducted 16S rRNA sequencing on stool samples from 94 CRC patients and employed the linear discriminant analysis effect size algorithm to identify distinct gut microbiota between KRAS mutant and KRAS wild-type CRC patients. Transcriptome sequencing data from nine CRC patients were transformed into a matrix of immune infiltrating cells, which was then utilized to explore KRAS mutation-associated biological functions, including Gene Ontology items and Kyoto Encyclopedia of Genes and Genomes pathways. Subsequently, we analyzed the correlations among these KRAS mutation-associated gut microbiota, host immunity, and KRAS mutation-associated biological functions. At last, we developed a predictive random forest (RF) machine learning model to predict the KRAS mutation status in CRC patients, based on the gut microbiota associated with KRAS mutation. We identified a total of 26 differential gut microbiota between both groups. Intriguingly, a significant positive correlation was observed between Bifidobacterium spp. and mast cells, as well as between Bifidobacterium longum and chemokine receptor CX3CR1. Additionally, we also observed a notable negative correlation between Bifidobacterium and GOMF:proteasome binding. The RF model constructed using the KRAS mutation-associated gut microbiota demonstrated qualified efficacy in predicting the KRAS phenotype in CRC. Our study ascertained the presence of 26 KRAS mutation-associated gut microbiota in CRC and speculated that Bifidobacterium may exert an essential role in preventing CRC progression, which appeared to correlate with the upregulation of mast cells and CX3CR1 expression, as well as the downregulation of GOMF:proteasome binding. Furthermore, the RF model constructed on the basis of KRAS mutation-associated gut microbiota exhibited substantial potential in predicting KRAS mutation status in CRC patients.IMPORTANCEGut microbiota has emerged as an essential player in the onset and development of colorectal cancer (CRC). However, the relationship between gut microbiota and KRAS mutation in CRC remains elusive. Our study not only identified a total of 26 gut microbiota associated with KRAS mutation in CRC but also unveiled their significant correlations with tumor-infiltrating immune cells, immune-related genes, and biological pathways (Gene Ontology items and Kyoto Encyclopedia of Genes and Genomes pathways). We speculated that Bifidobacterium may play a crucial role in impeding CRC progression, potentially linked to the upregulation of mast cells and CX3CR1 expression, as well as the downregulation of GOMF:Proteasome binding. Furthermore, based on the KRAS mutation-associated gut microbiota, the RF model exhibited promising potential in the prediction of KRAS mutation status for CRC patients. Overall, the findings of our study offered fresh insights into microbiological research and clinical prediction of KRAS mutation status for CRC patients.

Ultrasensitive SERS quantitative detection of antioxidants via diazo derivatization reaction and deep learning for signal fluctuation mitigation.

Synthetic antioxidants serve as essential protectors against oxidation and deterioration of edible oils, however, prudent evaluation is necessary regarding potential health risks associated with excessive intake. The direct adsorption of antioxidants onto conventional surface-enhanced Raman scattering (SERS) substrates is challenging due to the presence of phenolic hydroxyl groups in their molecular structures, resulting in weak Raman scattering signals and rendering direct SERS detection difficult. In this study, a diazo derivatization reaction was employed to enhance SERS signals by converting antioxidant molecules into azo derivatives, enabling the amplification of the weak Raman scattering signals through the strong vibrational modes induced by the N = N double bond. The resulting diazo derivatives were characterized using UV-visible absorption and infrared spectroscopy, confirming the occurrence of diazo derivatization of the antioxidants. The proposed method successfully achieved the rapid detection of three commonly used synthetic antioxidants, namely butylated hydroxyanisole (BHA), tert-butylhydroquinone (TBHQ), and propyl gallate (PG) on interfacial self-assembled gold nanoparticles. Furthermore, rapid predictions of BHA, PG, and TBHQ within the concentration range of 1 × 10-6 to 2 × 10-3 mol/L were achieved by integrating a convolutional neural network model. The predictive range of this model surpassed the traditional quantitative method of manually selecting characteristic peaks, with linear coefficients (R2) of 0.9992, 0.9997, and 0.9997, respectively. The recovery of antioxidants in real soybean oil samples ranged from 73.0 % to 126.4 %. Based on diazo derivatization, the proposed SERS method eliminates the need for complex substrates and enables the analysis and determination of synthetic antioxidants in edible oils within 20 min, providing a convenient analytical approach for quality control in the food industry.

Adavosertib-encapsulated metal-organic frameworks for p53-mutated gallbladder cancer treatment via synthetic lethality.

Adavosertib (ADA) is a WEE1 inhibitor that exhibits a synthetic lethal effect on p53-mutated gallbladder cancer (GBC). However, drug resistance due to DNA damage response compensation pathways and high toxicity limits further applications. Herein, estrone-targeted ADA-encapsulated metal-organic frameworks (ADA@MOF-EPL) for GBC synthetic lethal treatment by inducing conditional factors are developed. The high expression of estrogen receptors in GBC enables ADA@MOF-EPL to quickly enter and accumulate near the cell nucleus through estrone-mediated endocytosis and release ADA to inhibit WEE1 upon entering the acidic tumor microenvironment. Ultrasound irradiation induces ADA@MOF-EPL to generate reactive oxygen species (ROS), which leads to a further increase in DNA damage, resulting in a higher sensitivity of p53-mutated cancer cells to WEE1 inhibitor and promoting cell death via conditional synthetic lethality. The conditional factor induced by ADA@MOF-EPL further enhances the antitumor efficacy while significantly reducing systemic toxicity. Moreover, ADA@MOF-EPL demonstrates similar antitumor abilities in other p53-mutated solid tumors, revealing its potential as a broad-spectrum antitumor drug.

Wet bio-amniotic membrane plugging combined with transplantation in the treatment of small corneal perforations

ABSTRACT Purpose: Wet bio-amniotic membrane plugging combined with transplantation is a novel option that combined amniotic membrane plugging with amniotic membrane transplantation for the treatment of small corneal perforations. This study aimed to evaluate the efficacy of wet bio-amniotic membrane plugging in the treatment of small corneal perforations and compared it with that of the penetrating keratoplasty procedure. Methods: Forty patients (41 eyes) with small corneal perforations <3 mm in diameter treated at our hospital between July 2018 and January 2021 were retrospectively included. Among them, 21 eyes were treated with wet bio-amniotic membrane plugging (wet bio-amniotic membrane plugging group), and 20 eyes were treated with penetrating keratoplasty procedure (penetrating keratoplasty procedure group). The best-corrected visual acuity, anterior chamber formation, corneal thickness, primary disease control, postoperative complications, and graft survival rate were assessed. Results: No significant difference in baseline characteristics was found between the wet bio-amniotic membrane plugging and penetrating keratoplasty procedure groups (p>0.05). The postoperative control rates of primary diseases in the wet bio-amniotic membrane plugging and penetrating keratoplasty procedure groups were 95.2% and 90.0%, respectively (p=0.481). Visual acuity was improved 6 months after the operation in the wet bio-amniotic membrane plugging group and was improved at postoperative 1 month in the penetrating keratoplasty procedure group. The formation time of the anterior chamber in the wet bio-amniotic membrane plugging group was significantly shorter than that in the penetrating keratoplasty procedure group (p=0.023). The corneal thickness of the two groups significantly increased 12 months after the operation; however, the degree of thickening in the penetrating keratoplasty procedure group was higher than that in the wet bio-amniotic membrane plugging group (p<0.001). During the follow-up, postoperative complications were not different between the two groups (p>0.999). Conclusion: The results suggest that wet bio-amniotic membrane plugging is effective and safe in the treatment of small corneal perforations. Thus, it can be used as an emergency treatment alternative to penetrating keratoplasty procedure for small corneal perforations.

Cucurbit[8]uril-mediated SERS plasmonic nanostructures with sub-nanometer gap for the identification and determination of estrogens.

The SERS intensity of analytes is primarily influenced by the density and distribution of hotspots, which are often difficult to manipulate or regulate. In this study, cucurbit[8]uril (CB[8]), a kind of rigid macrocyclic molecule, was introduced to achieve ~ 1-nm nanogap between gold nanoparticles to increase the density of SERS hotspots. Three kinds of estrogens (estrone (E1), bisphenol A (BPA), and hexestrol (DES)) which are molecules with weak SERS signals were targeted in the hotspots by CB[8] to further improve the sensitivity and selectivity of SERS. It was demonstrated that CB[8] can link gold nanoparticles together through carbonyl groups. In addition, the host-guest interaction of CB[8] and estrogens was proved from the nuclear magnetic resonance hydrogen and infrared spectra. In the presence of CB[8], the SERS intensities of E1, BPA, and DES were increased to 19-fold, 74-fold, and 4-fold, respectively, and the LOD is 3.75 µM, 1.19 µM, and 8.26 µM, respectively. Furthermore, the proposed SERS method was applied to actual milk sample analysis with recoveries of E1 (85.0 ~ 112.8%), BPA (83.0 ~ 103.7%), and DES (62.6 ~ 132.0%). It is expected that the proposed signal enlarging strategy can be applied to  other analytes after further development.

Different CT slice thickness and contrast-enhancement phase in radiomics models on the differential performance of lung adenocarcinoma.

BACKGROUND: To investigate the effects of computed tomography (CT) reconstruction slice thickness and contrast-enhancement phase on the differential diagnosis performance of radiomic signature in lung adenocarcinoma. METHODS: A total of 187 patients who had been pathologically confirmed with lung adenocarcinoma and nonadenocarcinoma were divided into a training cohort (n = 149) and validation cohort (n = 38). All the patients underwent contrast-enhanced CT and the images were reconstructed with different slice thickness. The radiomic features were extracted from different slice thickness and scan phase. The logistic regression (LR) algorithm was used to build a machine learning model for each group. The area under the curve (AUC) obtained from the receiver operating characteristic (ROC) curve and DeLong test was used to evaluate its discriminating performance. RESULTS: Finally, 34 image features and five semantic features were selected to establish a radiomics model. Based on the three contrast-enhanced CT phases and four reconstruction slice thickness, 12 groups of radiomics models showed good discrimination ability with the AUCs range from 0.9287 to 0.9631, sensitivity range from 0.8349 to 0.9083, specificity range from 0.825 to 0.925 in the training group. Similar results were observed in the validation group. However, there was no statistical significance between the different CT scan phase groups and different slice thickness (p > 0.05). CONCLUSIONS: The radiomic analysis of contrast-enhanced CT can be used for the differential diagnosis of lung adenocarcinoma. Moreover, different slice thickness and contrast-enhanced scan phase did not affect the discriminating ability in the radiomics models.

Hemin-Induced Death Models Hemorrhagic Stroke and Is a Variant of Classical Neuronal Ferroptosis.

Ferroptosis is a caspase-independent, iron-dependent form of regulated necrosis extant in traumatic brain injury, Huntington disease, and hemorrhagic stroke. It can be activated by cystine deprivation leading to glutathione depletion, the insufficiency of the antioxidant glutathione peroxidase-4, and the hemolysis products hemoglobin and hemin. A cardinal feature of ferroptosis is extracellular signal-regulated kinase (ERK)1/2 activation culminating in its translocation to the nucleus. We have previously confirmed that the mitogen-activated protein (MAP) kinase kinase (MEK) inhibitor U0126 inhibits persistent ERK1/2 phosphorylation and ferroptosis. Here, we show that hemin exposure, a model of secondary injury in brain hemorrhage and ferroptosis, activated ERK1/2 in mouse neurons. Accordingly, MEK inhibitor U0126 protected against hemin-induced ferroptosis. Unexpectedly, U0126 prevented hemin-induced ferroptosis independent of its ability to inhibit ERK1/2 signaling. In contrast to classical ferroptosis in neurons or cancer cells, chemically diverse inhibitors of MEK did not block hemin-induced ferroptosis, nor did the forced expression of the ERK-selective MAP kinase phosphatase (MKP)3. We conclude that hemin or hemoglobin-induced ferroptosis, unlike glutathione depletion, is ERK1/2-independent. Together with recent studies, our findings suggest the existence of a novel subtype of neuronal ferroptosis relevant to bleeding in the brain that is 5-lipoxygenase-dependent, ERK-independent, and transcription-independent. Remarkably, our unbiased phosphoproteome analysis revealed dramatic differences in phosphorylation induced by two ferroptosis subtypes. As U0126 also reduced cell death and improved functional recovery after hemorrhagic stroke in male mice, our analysis also provides a template on which to build a search for U0126's effects in a variant of neuronal ferroptosis.SIGNIFICANCE STATEMENT Ferroptosis is an iron-dependent mechanism of regulated necrosis that has been linked to hemorrhagic stroke. Common features of ferroptotic death induced by diverse stimuli are the depletion of the antioxidant glutathione, production of lipoxygenase-dependent reactive lipids, sensitivity to iron chelation, and persistent activation of extracellular signal-regulated kinase (ERK) signaling. Unlike classical ferroptosis induced in neurons or cancer cells, here we show that ferroptosis induced by hemin is ERK-independent. Paradoxically, the canonical MAP kinase kinase (MEK) inhibitor U0126 blocks brain hemorrhage-induced death. Altogether, these data suggest that a variant of ferroptosis is unleashed in hemorrhagic stroke. We present the first, unbiased phosphoproteomic analysis of ferroptosis as a template on which to understand distinct paths to cell death that meet the definition of ferroptosis.

National-scale distribution of micro(meso)plastics in farmland soils across China: Implications for environmental impacts.

Microplastics (MPs) pollution is increasingly appreciated as a significant environmental issue, however, the large-scale pattern of MPs in farmland soils and its associated environmental impacts are unknown. This study investigated a national-scale distribution of micro(meso)plastics (MMPs) in the soil of 30 farmlands across China. The abundance of MMPs in soils was 25.56-2067.78 items kg-1, with a mean of 358.37 items kg-1, i.e. 6.79 mg kg-1 or 0.0007% after mass conversion. MPs accounted for 93.1% of MMPs, the abundance varied greatly among different regions, high in arid or semi-arid north but relatively low in mild southwest regions. Major MPs included polypropylene, polyethylene, and polyester, tending to decrease in abundance from surface to deeper soil layers. Further, meta-analysis revealed that MPs exposure influenced bulk density, soil enzymes including fluorescein diacetate hydrolase (FDAse) and urease, and crop biomass, and minimum effective concentrations (MEC) were in the range of 0.0040-10%. We found that actual abundance in the national-scale soils was lower than MEC, but partly overlapped or close, which implies various degrees of environmental impacts. These findings disclose the national-scale pollution pattern of MPs in farmlands and its latent risks to soil environments and crop growth.

Comparison of modified corneal cross-linking with intrastromal voriconazole for the treatment of fungal corneal ulcer.

The present study aimed to evaluate the efficacy of modified corneal cross-linking (CXL) for the treatment of fungal corneal ulcers compared with that following intrastromal voriconazole injection. In total, 31 patients with fungal corneal ulcers treated at The General Hospital of Northern Theater Command between October 2017 and October 2019 were enrolled. Among them, 10 eyes were treated with ultraviolet A (UV-A)/riboflavin CXL (CXL group), whilst 21 eyes were treated with debridement combined with intrastromal voriconazole (stromal injection group). Preoperative microbiological examination was performed in both groups, and evaluated using Fisher's exact test. Postoperatively, infection control and total efficacy rates, localized lesion, ulcer healing rate 1 week after surgery, visual acuity and complications were evaluated using Fisher's exact test, however visual acuity was analyzed by mixed-model ANOVA. The results showed that the pre-operative species distribution between the CXL and stromal injection groups did not significantly differ. The infection control rate in the CXL group was notably higher compared with that in the stromal injection group (P=0.04). Furthermore, the total efficacy rate in the CXL group was also markedly higher compared with that in the stromal injection group, though no statistically significant differences were observed. Localized lesions were observed in nine eyes (90.0%) in the CXL group and nine eyes (42.9%) in the stromal injection group (P=0.02). However, the rate of ulcer healing at 1 week postoperatively and the logarithm of the minimum angle of resolution (logMAR) of visual acuity were not found to be significantly different between the two groups. In terms of complications, with the exception of one patient in the CXL group exhibiting loss of corneal transparency and one patient in the stromal injection group presenting with partial corneal thinning, no other forms of complications were observed. In conclusion, the present study suggested that CXL could have a beneficial impact for treating fungal corneal ulcers in the aspects of infection control, localized lesions and accelerated epithelialization. In addition, except the loss of corneal transparency, this treatment approach could be applied with reduced risks of adverse events.

Comparative Study on the Efficacy of Frozen Amniotic Membrane Transplantation and Lamellar Keratoplasty in the Treatment of Mooren Ulcer.

OBJECTIVE: To compare of the clinical efficacy of frozen amniotic membrane transplantation (AMT) and lamellar keratoplasty (LKP) in the treatment of Mooren ulcer. METHOD: Forty patients (42 eyes) with Mooren's ulcer in our hospital from January 2010 to January 2019 were divided into frozen AMT group (20 eyes) and LKP group (22 eyes). Comparative observation of post-operative best corrected visual acuity (BCVA), corneal epithelial healing time, corneal epithelialization time, ulcer healing, corneal transparency, corneal graft transparency, neovascularization and original disease recurrence were observed. RESULTS: The average BCVA at post-operative 6 and 12 months in LKP group were significantly lower than AMT group (P < 0.05). The ulcer healing rates in LKP group (63.6) were significantly higher than AMT group (30) (P < 0.05). The corneal epithelialization time of LKP group were 9.55 ±â€Š1.26 days. The corneal epithelial healing time of AMT group were 13.50 ±â€Š2.21 days. Nine cases were corneal graft transparency grade 0, and 13 cases were grade I. Three eyes in AMT group were corneal transparency grade 0, 7 were grade I and 10 were grade II. Corneal neovascularization were observed in 3 eyes in AMT group and 4 eyes in LKP group. The original disease recurrence rates in LKP group (50) were significantly higher than AMT group (20) (P < 0.05). Four cases of primary corneal transplantation failure were observed in LKP group. CONCLUSION: Lamellar keratoplasty group obtained significantly better BCVA during follow-up and faster healing time than the frozen AMT group while frozen AMT group had lower original disease recurrence rates than LKP group.

Electromagnetized-Nanoparticle-Modulated Neural Plasticity and Recovery of Degenerative Dopaminergic Neurons in the Mid-Brain.

The degeneration of dopaminergic neurons is a major contributor to the pathogenesis of mid-brain disorders. Clinically, cell therapeutic solutions, by increasing the neurotransmitter dopamine levels in the patients, are hindered by low efficiency and/or side effects. Here, a strategy using electromagnetized nanoparticles to modulate neural plasticity and recover degenerative dopamine neurons in vivo is reported. Remarkably, electromagnetic fields generated by the nanoparticles under ultrasound stimulation modulate intracellular calcium signaling to influence synaptic plasticity and control neural behavior. Dopaminergic neuronal functions are reversed by upregulating the expression tyrosine hydroxylase, thus resulting in ameliorating the neural behavioral disorders in zebrafish. This wireless tool can serve as a viable and safe strategy for the regenerative therapy of the neurodegenerative disorders.

Prevalence of microplastics in animal-based traditional medicinal materials: Widespread pollution in terrestrial environments.

Microplastics (MPs) pollution is an emerging environmental and health concern. MPs have been extensively observed in the aquatic environment, yet rarely investigated in the terrestrial ecosystem, especially in relation to health risks. To evaluate potential MPs pollution in land-dwelling animal medicine materials, we collected 20 types of small animal-based medicinal materials and 10 types of available fresh terrestrial animals from eight different regions in China. MPs were found in all medicinal materials with an average incidence rate of 94.67%. The abundance of MPs was in the range of 1.80 ± 0.38 to 7.80 ± 0.83 items/individual or 1.59 ± 0.33 to 43.56 ± 9.22 items/g (dry weight), with polymer distribution by polyethylene terephthalate (40.45%), rayon (30.64%), polyethylene (10.11%), nylon (7.35%), polypropylene (5.93%), and polyvinyl chloride (5.52%). The majority of MPs were microfibers (84.68%), with 15.32% of fragments. Moreover, MPs were directly observed in the intestine, detected in all ten types of fresh medicinal animals with the abundance of 0.83 ± 0.35 to 3.42 ± 0.46 items/individual. Furthermore, significant positive correlations (R: 0.32-0.99, p < 0.05) of MPs characteristics were found between medicinal materials and fresh animals, including shape, size, color, and polymer distribution of MPs. The results support that MPs in the medicinal materials were likely derived from living animals. This study demonstrates the prevalence of MPs in animal-based, traditional medicinal materials, and also suggests widespread MPs pollution in terrestrial environments and latent health risks.

The drug adaptaquin blocks ATF4/CHOP-dependent pro-death Trib3 induction and protects in cellular and mouse models of Parkinson's disease.

Identifying disease-causing pathways and drugs that target them in Parkinson's disease (PD) has remained challenging. We uncovered a PD-relevant pathway in which the stress-regulated heterodimeric transcription complex CHOP/ATF4 induces the neuron prodeath protein Trib3 that in turn depletes the neuronal survival protein Parkin. Here we sought to determine whether the drug adaptaquin, which inhibits ATF4-dependent transcription, could suppress Trib3 induction and neuronal death in cellular and animal models of PD. Neuronal PC12 cells and ventral midbrain dopaminergic neurons were assessed in vitro for survival, transcription factor levels and Trib3 or Parkin expression after exposure to 6-hydroxydopamine or 1-methyl-4-phenylpyridinium with or without adaptaquin co-treatment. 6-hydroxydopamine injection into the medial forebrain bundle was used to examine the effects of systemic adaptaquin on signaling, substantia nigra dopaminergic neuron survival and striatal projections as well as motor behavior. In both culture and animal models, adaptaquin suppressed elevation of ATF4 and/or CHOP and induction of Trib3 in response to 1-methyl-4-phenylpyridinium and/or 6-hydroxydopamine. In culture, adaptaquin preserved Parkin levels, provided neuroprotection and preserved morphology. In the mouse model, adaptaquin treatment enhanced survival of dopaminergic neurons and substantially protected their striatal projections. It also significantly enhanced retention of nigrostriatal function. These findings define a novel pharmacological approach involving the drug adaptaquin, a selective modulator of hypoxic adaptation, for suppressing Parkin loss and neurodegeneration in toxin models of PD. As adaptaquin possesses an oxyquinoline backbone with known safety in humans, these findings provide a firm rationale for advancing it towards clinical evaluation in PD.

Comparison of the Clinical Efficacy of Boston Keratoprosthesis Type I and Repetitive Penetrating Keratoplasty for Refractory Keratopathy.

OBJECTIVE: To compare the clinical efficacy of Boston Keratoprosthesis type I (B-KProI) and penetrating keratoplasty (PKP) for patients with refractory keratopathy after 1failed PKP in China. METHOD: The 42 consecutive cases with refractory keratopathy after 1 failed PKP, from July 2010 to December 2014, were divided into 2 groups according to the surgical method: KPro group (n = 21) and PKP group (n = 21). Visual acuity (LogMAR), corneal graft transparency, postoperative complications and corneal graft survival rate were observed. The follow-up time was 2 years. The Kaplan-Meier curve was used to analyze the survival rate of the two groups of corneal grafts. RESULTS: The average best corrected visual acuity (BCVA) at 1, 6, 12, 18, and 24 months in KPro group were significantly lower than PKP group (P < 0.01). The best postoperative visual acuity and BCVA at postoperative 2 years in KPro group were lower than PKP group. The success rate of KPro group (86%) were significantly higher than PKP group (43%) (P < 0.01). There were no significant differences in indicate of complications in 2 groups including secondary glaucoma, secondary infectious corneal ulcer, corneal graft melting and endophthalmitis (P > 0.05). CONCLUSION: Compared with repetitive PKP, B-KProI had a higher success rate, improved postoperative visual acuity, reduced postoperative corneal transplant rejection rates and improved corneal graft survival rate.

Selenium Drives a Transcriptional Adaptive Program to Block Ferroptosis and Treat Stroke.

Ferroptosis, a non-apoptotic form of programmed cell death, is triggered by oxidative stress in cancer, heat stress in plants, and hemorrhagic stroke. A homeostatic transcriptional response to ferroptotic stimuli is unknown. We show that neurons respond to ferroptotic stimuli by induction of selenoproteins, including antioxidant glutathione peroxidase 4 (GPX4). Pharmacological selenium (Se) augments GPX4 and other genes in this transcriptional program, the selenome, via coordinated activation of the transcription factors TFAP2c and Sp1 to protect neurons. Remarkably, a single dose of Se delivered into the brain drives antioxidant GPX4 expression, protects neurons, and improves behavior in a hemorrhagic stroke model. Altogether, we show that pharmacological Se supplementation effectively inhibits GPX4-dependent ferroptotic death as well as cell death induced by excitotoxicity or ER stress, which are GPX4 independent. Systemic administration of a brain-penetrant selenopeptide activates homeostatic transcription to inhibit cell death and improves function when delivered after hemorrhagic or ischemic stroke.

Post-operative outcomes associated with Boston type 1 keratoprosthesis implantation in Northeast China.

The aim of the present study was to investigate the post-operative outcomes associated with Boston type 1 keratoprosthesis (Kpro-1) implantation in the treatment of patients with corneal blindness in Northeast China. Clinical data of patients who had undergone Kpro-1 implantation between July 2010 and November 2014 were retrospectively collected. The visual performance, implant retention and post-surgical complications were recorded for each patient. A total of 20 patients (20 eyes) with corneal blindness were included in the study. Prior to surgery, the patients exhibited poor vision and decreased levels of light perception. At 3 days, 1 month, 6 months, 1 year and 2 years post-surgery, logarithm of the minimum angle of resolution values were significantly decreased compared with the pre-operative values. The initial Kpro-1 implants were retained in 16 eyes. Regarding the post-operative complications, six patients exhibited retroprosthetic membrane formation, two patients presented with endophthalmitis, two patients developed secondary glaucoma, two patients experienced optical cylinder detachment, two patients presented with corneal melting, three patients had retinal detachment, three patients developed corneal ulcers and one patient had secondary optic neuropathy. Overall, the results of the present study suggested that implantation with Kpro-1 may represent an alternative therapeutic strategy for patients following previously failed keratoplasty in Northeast China. Serious complications associated with Kpro-1 implantation are common, and thus, suitable patient selection, continuous follow-up and early treatment interventions are recommended.

N-acetylcysteine targets 5 lipoxygenase-derived, toxic lipids and can synergize with prostaglandin E2 to inhibit ferroptosis and improve outcomes following hemorrhagic stroke in mice.

OBJECTIVES: N-acetylcysteine (NAC) is a clinically approved thiol-containing redox modulatory compound currently in trials for many neurological and psychiatric disorders. Although generically labeled as an "antioxidant," poor understanding of its site(s) of action is a barrier to its use in neurological practice. Here, we examined the efficacy and mechanism of action of NAC in rodent models of hemorrhagic stroke. METHODS: Hemin was used to model ferroptosis and hemorrhagic stroke in cultured neurons. Striatal infusion of collagenase was used to model intracerebral hemorrhage (ICH) in mice and rats. Chemical biology, targeted lipidomics, arachidonate 5-lipoxygenase (ALOX5) knockout mice, and viral-gene transfer were used to gain insight into the pharmacological targets and mechanism of action of NAC. RESULTS: NAC prevented hemin-induced ferroptosis by neutralizing toxic lipids generated by arachidonate-dependent ALOX5 activity. NAC efficacy required increases in glutathione and is correlated with suppression of reactive lipids by glutathione-dependent enzymes such as glutathione S-transferase. Accordingly, its protective effects were mimicked by chemical or molecular lipid peroxidation inhibitors. NAC delivered postinjury reduced neuronal death and improved functional recovery at least 7 days following ICH in mice and can synergize with clinically approved prostaglandin E2 (PGE2 ). INTERPRETATION: NAC is a promising, protective therapy for ICH, which acted to inhibit toxic arachidonic acid products of nuclear ALOX5 that synergized with exogenously delivered protective PGE2 in vitro and in vivo. The findings provide novel insight into a target for NAC, beyond the generic characterization as an antioxidant, resulting in neuroprotection and offer a feasible combinatorial strategy to optimize efficacy and safety in dosing of NAC for treatment of neurological disorders involving ferroptosis such as ICH. Ann Neurol 2018;84:854-872.

Excisional keratectomy combined with focal cryotherapy and amniotic membrane inlay for recalcitrant filamentary fungal keratitis: A retrospective comparative clinical data analysis.

The aim of the present study was to investigate the efficacy of a novel surgical intervention, excisional keratectomy combined with focal cryotherapy and amniotic membrane inlay (EKCAI), for the treatment of recalcitrant filamentary fungal keratitis. A retrospective analysis was performed of patients who underwent excisional keratectomy combined with conjunctival flap inlay (EKCFI), EKCAI or therapeutic penetrating keratoplasty (TPK) from January 2006 to January 2011. Recalcitrance was determined as being unresponsive to standard medical antifungal therapy for at ≥1 week. Outcome measures among the three intervention modalities were compared. A total of 128 patients had a follow-up of ≥1 year after the primary intervention. The success rates of interventions at 1-year follow-up were 58.33% in the EKCFI group, 88.37% in the EKCAI group and 93.44% in the TPK group (P<0.0002). The preoperative visual acuity of the three groups were similar (P=0.6458), while the postoperative best-corrected visual acuity (BCVA) of patients without recurrence was significantly different among the three groups 3 months after surgery. The best postoperative BCVA was found in the TPK group, while the worst was in the EKCFI group. In conclusion, EKCAI does not require donor cornea, is straightforward surgically, and has a favorable success rate compared with EKCFI.

High MMP-9 Expression May Contribute to Retroprosthetic Membrane Formation after KPro Implantation in Rabbit Corneal Alkali Burn Model.

Purpose. To evaluate aqueous humor MMP-9 levels in alkali-burned rabbit cornea following KPr implantation and their roles in RPMs formation. Methods. Left eyes of 36 rabbits received a deep corneal alkali wound. 12 corneas were implanted with KPro and the other 24 control corneas were either penetrating keratoplasty or left without keratoplasty. Aqueous humor MMP-9 and TIMP-1 levels were determined and RPMs were obtained for histopathological and ultrastructural examination. Results. Alkali exposure induced significant increase in aqueous humor MMP-9 level and the data were further enhanced by KPro implantation. By contrast, TMIP-1 levels in aqueous humor showed a decreased trend following corneal alkali burn and KPro surgery. RPMs were developed in 5 out of 10 cases of KPro successfully implanted eyes. Histopathology showed the presence of a large number of fibroblasts and collagen fibers arranged irregularly with inflammatory cells infiltration, and an ingrowth of new blood vessels in this retrokeratoprosthesis fibrous tissue. Immunohistochemical analysis showed positive stain of RPMs for both MMP-9 and TIMP-1. Aqueous humor MMP-9 levels were significantly higher in RPM group postoperatively, while TIMP-1 levels were comparatively lower than that of No-RPM group. Conclusions. Our study evidenced the potential pathophysiological role of MMP-9 expression in RPM formation following KPro implantation.