Two ferroptosis-specific expressed genes NOX4 and PARP14 are considered as potential biomarkers for the diagnosis and treatment of diabetic retinopathy and atherosclerosis.

OBJECTIVES: Both Diabetic retinopathy (DR) and Atherosclerosis (AS) are common complications in patients with diabetes, and they share major pathophysiological similarities and have a common pathogenesis. Studies performed to date have demonstrated that ferroptosis plays a vital part in the occurrence and development of DR and AS, but its mechanism in the two diseases remains poorly understood. METHODS: DR Chip data (GSE60436 and GSE102485) and AS chip data (GSE100927 and GSE57691) were obtained from the Gene Expression Omnibus (GEO) database. The screening of the differential expression genes (DEGs) was analyzed using the limma package, and the genes related to ferroptosis were obtained from the FerrDb V2 database. Two key genes (NOX4 and PARP14) were identified through external datasets validation and receiver operating characteristic (ROC) curve analysis. Gene Ontology (GO) and Gene Set Enrichment Analysis (GSEA) were used to conduct a functional enrichment analysis, and miRNA-mRNA networks were established. The CIBERSORT algorithm was applied to identify the immune cell infiltration between the disease group and control group. Next, the correlations between key genes and infiltrating immune cells were investigated by the Spearman method. Finally, the correlation between 2 key genes and ferroptosis markers was confirmed. RESULTS: Nine ferroptosis differentially expressed genes (DE-FRGs) between DR and AS were identified in this study. NOX4 and PARP14 were selected as key genes for further analysis by external datasets and ROC curve analysis. The key genes NOX4, PARP14 and their correlated genes (such as CYBA, NOX1, NOX3, CYBB, PARP9, PARP10, and PARP15) are mainly enriched in oxidoreductase activity, protein ADP-ribosylation, superoxide metabolic process, reactive oxygen species metabolic process, PID pathway, and VEGFA-VEGFR2 pathway. A miRNA-mRNA network was constructed, and we got 12 miRNAs correlated with the target gene NOX4, 38 miRNAs correlated with the target gene PARP14. Three common miRNAs (hsa-miR-1-3p, hsa-miR-129-2-3p, and hsa-miR-155-5p) were observed in the network. Immune infiltration analysis displayed that activated B cell, MDSC, and Type 17 T helper cell are the common immune cells involved in the immune infiltration process of DR and AS. The results revealed that there are significant correlations between two key genes and most ferroptosis marker genes no matter in DR or AS. CONCLUSION: Ferroptosis-related genes NOX4 and PARP14 may be common biomarkers of DR and AS. Both were associated with immune infiltration in patients with DR and AS. Our data provide a theoretical basis for the early diagnosis and immunotherapy of the two diseases.

Branch retina vein occlusion combined with angle-closure glaucoma is associated with a mutation in BEST1: a case report.

BACKGROUND: It is rare for a patient to be diagnosed with branch retina vein occlusion (BRVO), angle-closure glaucoma (ACG) and autosomal recessive bestrophinopathy (ARB). ARB is strongly associated with ACG. Although glaucoma is a significant risk factor for RVO, there is a plausible relationship between ACG and BRVO. To discuss correlation of these diseases is necessary. CASE PRESENTATION: The genetic testing and medical treatment of a patient with ocular fundus diseases and ACG were recorded. We present a 47-year-old male patient with BRVO who was diagnosed with angle-closure glaucoma and a homozygous mutation of c.140G > A (p.R47H) in BEST1. Intravitreal ranibizumab was administered in combination with three antiglaucomatous eyedrops to lower intraocular pressure (IOP) in the right eye. One month later, BCVA improved to 0.3. IOP was controlled at 13 mmHg. CONCLUSIONS: ACG was likely combined to ARB, while there's a plausible relationship between ACG and BRVO.

[CO2 laser moxibustion for endometriosis related pelvic pain of cold coagulation and blood stasis: a randomized controlled trial].

OBJECTIVE: To observe the clinical therapeutic effect of CO2 laser moxibustion on endometriosis related pelvic pain of cold coagulation and blood stasis. METHODS: A total of 76 patients with endometriosis related pelvic pain of cold coagulation and blood stasis were randomized into a laser moxibustion group and a sham laser moxibustion group, 38 cases in each group. In the laser moxibustion group, moxibustion was applied at bilateral Zigong (EX-CA 1) using CO2 laser moxibustion instrument. In the sham laser moxibustion group, the manipulation of moxibustion was same as the laser moxibustion group, without laser output. The treatment was given once every other day, 30 min each time, 3 times a week for 4 weeks in both groups. Before and after treatment and follow-up of 3 months after treatment, the scores of Gracely box scale (GBS) and visual analogue scale (VAS) were observed, the usage of non-steroidal anti-inflammatory drug for the duration of the treatment and the average days of taking drugs were recorded in both groups. RESULTS: Compared before treatment, the GBS and VAS scores were decreased after treatment and during follow-up in the laser moxibustion group (P<0.05), while those in the sham moxibustion group had no significant differences (P>0.05). Compared with the sham moxibustion group, the GBS and VAS scores were decreased after treatment and during follow-up (P<0.05), the cases and average days of taking drugs were less in the laser moxibustion group (P<0.05). CONCLUSION: CO2 laser moxibustion can improve the pain symptom in patients with endometriosis related pelvic pain of cold coagulation and blood stasis, and reduce the use of analgesic drugs.

Design and Methodology of a Multi-Centre Clinical Trial of Low Dose Laser Cycloplasty for the Treatment of Malignant Glaucoma in China.

PURPOSE: To summarize the design and methodology of a trial designed to evaluate the efficacy and safety of low dose laser cycloplasty (LCP) in treating malignant glaucoma. METHODS: Prospective, multicentre, non-controlled clinical trial. Subjects were recruited from eight ophthalmic centers in China. The target sample size was 34. Patients aged >18 years with a clinical diagnosis of malignant glaucoma inadequately controlled on medical therapy or malignant glaucoma recurrence after topical cycloplegics withdrawal were enrolled. All patients underwent LCP under retrobulbar anesthesia or sub-Tenon anesthesia. LCP is a treatment adopting few laser points (1100-2000 mW energy, 2000 milliseconds duration) that cauterizes and remodels the ciliary body over two clock hour-positions, which may relieve the ciliary ring block. Follow-up is planned for a period of 12 months. The primary outcome is the resolution of malignant glaucoma which is defined as central anterior chamber deepening after LCP. CONCLUSION: The Malignant Glaucoma Treatment trial (MGTT) will be the first prospective trial providing evidence of a treatment for malignant glaucoma. It intends to provide clinicians an optional, easy and convenient treatment for malignant glaucoma patients. Detailed morphological and biometric information collected during the study period will also help provide experience for the outcomes of malignant glaucoma. TRIAL REGISTRATION NUMBER: ChiCTR1800017960.

Does Cataract Surgery Improve the Progression of Age-Related Macular Degeneration? A Meta-Analysis.

PURPOSE: Cataract and age-related macular degeneration (AMD) are the common causes of blindness in the elderly. Although cataract surgery is the most effective treatment for cataract, some clinicians suspect that such interventions may accelerate the progression of AMD. Therefore, we carried out this meta-analysis to focus on demonstrating the effectiveness and safety of cataract surgery in eyes with AMD. METHODS: We performed a systematic literature search in the PubMed, EMBASE, and Cochrane Library databases, and the electronic databases were last searched in January 2019. We planned to include cohort trials of eyes affected by both cataract and AMD in which cataract surgery would be compared to no surgery. Two reviewers independently evaluated the search results against the inclusion and exclusion criteria. 8 trials were included for this meta-analysis. RESULTS: We used the Stata/12.0 to integrate the data that was extracted from the articles. Eight cohort trials with data from different study populations were included. In random effects model, the relative risk (RR) for the progression of AMD is 1.194 (95% CI 0.897-1.591). As for those grouped according to the follow-up year, the RR for longer than five years was 1.372 (95% CI 1.062-1.772). CONCLUSION: We could draw out such a conclusion that there is still a positive correlation between cataract surgery and the progression of AMD, especially for the Asians. However, based on the current results, it is not possible to draw conclusions from existing studies on the impact of cataract surgery on early AMD development.

Copper-Catalyzed Perfluoroalkylation of Allyl Phosphates with Stable Perfluoroalkylzinc Reagents.

A general and practical method for copper-catalyzed cross-coupling of allyl phosphates with stable perfluoroalkylzinc reagents has been developed. The reaction proceeds under mild reaction conditions with high efficiency, good functional group tolerance, and high regio- and stereoselectivities and provides general, straightforward, and useful access to allyl-perfluoroalkyl compounds. Preliminary mechanistic studies reveal that the allyl copper intermediate may be involved in the catalytic cycle.

Streptozotocin­induced diabetic mice exhibit reduced experimental choroidal neovascularization but not corneal neovascularization.

The present study aimed to investigate the effects of diabetes mellitus (DM) on the generation of experimental corneal neovascularization (CrNV) and choroidal neovascularization (ChNV). Diabetes was induced in mice by intraperitoneal injection of streptozotocin (STZ). Experimental CrNV and ChNV were induced by alkali injury and laser photocoagulation, respectively. CrNV and ChNV were compared between the STZ­induced diabetic mice and control mice two weeks after injury. Relative expression of angiogenic factors was quantified by reverse transcription­quantitative polymerase chain reaction, and progenitor cell or macrophage accumulation in the early phase following injury was examined by flow cytometric analysis. Compared with the alkali­injured normal mice, the alkali­injured diabetic mice (STZ­induced) exhibited no significant difference in CrNV occurrence, whereas the laser­injured diabetic mice exhibited significantly reduced levels of ChNV compared with those of the laser­injured control animals. The laser­induced intrachoroidal mRNA expression levels of angiogenic factors, including vascular endothelial growth factor, hypoxia­induced factor­1α, chemokine (C­C motif) ligand 3, and stromal cell­derived factor­1α, were reduced in the laser­injured diabetic mice when compared with laser­injured control mice. Furthermore, the laser­induced intrachoroidal infiltration of c­Kit+ progenitor cells was impaired in the laser­injured diabetic mice compared with the laser­injured control mice. Overall, diabetes did not exert a significant effect on the generation of experimental CrNV. However, diabetes reduced laser­induced ChNV through downregulation of intrachoroidal progenitor cell infiltration and angiogenic factor expression.

Relationship between filtering bleb vascularization and surgical outcomes after trabeculectomy: an optical coherence tomography angiography study.

PURPOSE: To explore the relationship between the bleb vasculature and surgical outcome after trabeculectomy (TRAB) using optical coherence tomography angiography (OCT-A). METHODS: A prospective study was conducted, which included 26 eyes of 26 primary glaucoma patients in the final analysis. Thereinto, six patients underwent TRAB combined 5-FU and 12 patients received subconjunctival 5-FU injection postoperation. The bleb vessel was evaluated using OCT-A 1 week, 2 weeks, 1 month, 3 months, and 6 months after TRAB. Intraocular pressure (IOP), filtering bleb height, and bleb wall thickness were recorded at the same time. Pearson's correlation analysis and linear regression analysis were performed to determine the correlation of the vessel area data with other parameters. RESULTS: Compared with vessel area 1 week after surgery, there was significant increase of the vessel area (△vessel area) 2 weeks (11.13 ± 11.91%, p < 0.05) and 1 month (16.91 ± 14.85%, p < 0.0001) after surgery in all patients. The △vessel area was significantly greater in acute angle closure (AAC) and primary angle closure glaucoma (PACG) 1-month post-TRAB as compared with that 1 week (p < 0.05). The results indicated that the △vessel area 1-month post-TRAB was positive correlated with IOP 6-month post-TRAB (ß = 3.88, p = 0.042). CONCLUSIONS: Filtering bleb vascularization evaluation using OCT-A could potentially predict IOP 6-month post-TRAB. Surgery effect predicted by filtering bleb vascularization detection is conducive to the select specific postoperative intervention to improve the success rate of TRAB.

LncRNAs expression in preeclampsia placenta reveals the potential role of LncRNAs contributing to preeclampsia pathogenesis.

BACKGROUND: Long non-coding RNAs (lncRNAs) are an important class of pervasive genes involved in a variety of biological functions. They are aberrantly expressed in many types of diseases. In this study, we aimed to investigate the lncRNA profiles in preeclampsia. Preeclampsia has been observed in patients with molar pregnancy where a fetus is absent, which demonstrate that the placenta is sufficient to cause this condition. Thus, we analyzed the lncRNA profiles in preeclampsia placentas. METHODOLOGY/PRINCIPAL FINDINGS: In this study, we described the lncRNA profiles in six preeclampsia placentas (T) and five normal pregnancy placentas (N) using microarray. With abundant and varied probes accounting for 33,045 LncRNAs in our microarray, 28,443 lncRNAs that were expressed at a specific level were detected. From the data, we found 738 lncRNAs that were differentially expressed (≥ 1.5-fold-change) among preeclampsia placentas compared with controls. Coding-non-coding gene co-expression networks (CNC network) were constructed based on the correlation analysis between the differentially expressed lncRNAs and mRNAs. According to the CNC network and GO analysis of differentially expressed lncRNAs/mRNAs, we selected three lncRNAs to analyze the relationship between lncRNAs and preeclampsia. LOC391533, LOC284100, and CEACAMP8 were evaluated using qPCR in 40 preeclampsia placentas and 40 controls. These results revealed that three lncRNAs were aberrantly expressed in preeclampsia placentas compared with controls. CONCLUSIONS/SIGNIFICANCE: Our study is the first study to determine the genome-wide lncRNAs expression patterns in preeclampsia placenta using microarray. These results revealed that clusters of lncRNAs were aberrantly expressed in preeclampsia placenta compared with controls, which indicated that lncRNAs differentially expressed in preeclampsia placenta might play a partial or key role in preeclampsia development. Misregulation of LOC391533, LOC284100, and CEACAMP8 might contribute to the mechanism underlying preeclampsia. Taken together, this study may provide potential targets for the future treatment of preeclampsia and novel insights into preeclampsia biology.