Aurora kinase B disruption suppresses pathological retinal angiogenesis by affecting cell cycle progression.

PURPOSE: The detrimental effects of pathological angiogenesis on the visual function are indisputable. Within a prominent role in chromosome segregation and tumor progression, aurora kinase B (AURKB) assumes a prominent role. However, its role in pathological retinal angiogenesis remains unclear. This study explores this latent mechanism. METHODS: To inhibit AURKB expression, we designed specific small interfering RNAs targeting AURKB and transfected them into vascular endothelial cells. Barasertib was selected as the AURKB inhibitor. The anti-angiogenic effects of both AURKB siRNA and barasertib were assessed in vitro by cell proliferation, transwell migration, and tube formation. To evaluate the angiogentic effects of AURKB in vivo, neonatal mice were exposed to 75% oxygen followed by normoxic repositioning to establish an oxygen-induced retinopathy (OIR) model. Subsequently, phosphate-buffered saline and barasertib were administered into OIR mice via intravitreal injection. The effects of AURKB on cell cycle proteins were determined by western blot analysis. RESULTS: We found that AURKB was overexpressed during pathological angiogenesis. AURKB siRNA and barasertib significantly inhibited endothelial cell proliferation, migration, and tube formation in vitro. Furthermore, AURKB inhibition attenuated retinal angiogenesis in the OIR model. A possible mechanism is the disruption of cell cycle by AURKB inhibition. CONCLUSION: In conclusion, AURKB significantly influenced pathological retinal angiogenesis, thereby presenting a promising therapeutic target in ocular neovascular diseases.

Visual Outcome after Anti-Vascular Epithelial Growth Factor Therapy Using New Classification of Diabetic Macular Edema by Optical Coherence Tomography.

INTRODUCTION: The aim of the study was to examine alterations in visual acuity in patients with diabetic macular edema (DME), classified according to the TCED-HFV optical coherence tomography (OCT) system, following anti-vascular epithelial growth factor (VEGF) therapy. METHODS: The medical records of patients with DME receiving anti-VEGF therapy were retrospectively reviewed. Patients were divided into four groups according to the TCED-HFV OCT classification. Patient demographic and clinical characteristics and best-corrected visual acuity (BCVA) before and after treatment were compared among the groups. RESULTS: The BCVA before treatment was 0.49 ± 0.18, 0.81 ± 0.41, 0.83 ± 0.41, and 0.82 ± 0.49 in the early DME, advanced DME, severe DME, and atrophic maculopathy groups, respectively. The BCVA in the early DME group was therefore significantly lower than that in the other three groups (p = 0.042). After treatment, the BCVA improved to 0.15 ± 0.17, 0.52 ± 0.31, 0.62 ± 0.32, and 0.69 ± 0.47 in the early DME, advanced DME, severe DME, and atrophic maculopathy groups, respectively (p < 0.005). There were some differences among patients in the four groups in terms of the duration of diabetes, percentage of hemoglobin A1c, and duration of hypertension. CONCLUSION: The TCED-HFV OCT classification of patients with DME is exact and functional and can allow the severity of DME, and its response to anti-VEGF therapy, to be estimated.

Graphene quantum dots rescue angiogenic retinopathy via blocking STAT3/Periostin/ERK signaling.

BACKGROUND: Pathological retinal angiogenesis resulting from a variety of ocular diseases including oxygen induced retinopathy, diabetic retinopathy and ocular vein occlusion, is one of the major reasons for vision loss, yet the therapeutic option is limited. Multiple nanoparticles have been reported to alleviate angiogenic retinopathy. However, the adverse effect cannot be ignored due to the relatively large scale. Graphene quantum dots (GQDs) have shown potential in drug delivery and have been proved biocompatible. In this study, Graphene quantum dots are extensively investigated for their application in angiogenic retinopathy therapy. RESULTS: We showed that GQDs were biocompatible nanomaterials in vitro and in vivo. The nanoparticles have a dose-dependent inhibitory effect on proliferation, migration, tube formation and sprouting of human umbilical vein endothelial cells (HUVECs). Further data show that GQDs could inhibit pathological retinal neovascularization in an oxygen-induced retinopathy (OIR) model. The data of RNA sequencing suggested that periostin is involved in this process. GQDs inhibit the expression of periostin via STAT3, and further regulated cell cycle-related protein levels through ERK pathway. The signaling pathway was conformed in vivo using OIR mouse model. CONCLUSIONS: The present study indicated that GQDs could be a biocompatible anti-angiogenic nanomedicine in the treatment of pathological retinal neovascularization via disrupting periostin/ERK pathway and subsequent cell cycle.

The use of modified keystone flap in periarticular or large superficial tumor resection surgery.

BACKGROUND AND OBJECTIVES: The keystone design perforator island flap (KDPIF) is often used to cover defects in reliable blood supply and similar skin patterns, but its mobility is limited, especially when the wound is large or occurs around joints. Here, we describe a modified KDPIF, boat-shaped flap. We added a V shape along the lateral arc, forming a V-Y flap on KDPIF's outer arc shapes like a sail. This paper also describes a clinical study to evaluate this method. METHOD: From September 2014 to March 2017, 31 patients were operated on using the boat-shaped flap in our department and were followed up annually with clinical evaluation. The wound locations included joints (n = 11), trunk (n = 18), and face (n = 2). Fifteen defects were ≥5 × 5 cm2 . RESULTS: After 6 to 24 months of follow-up, 29 patients had first-intention healing and were satisfied with the morphology and function. Secondary healing was observed in two patients, and the wounds were closed after dressing treatment for 2 weeks. CONCLUSION: The boat-shaped flap enhances the mobility and achieves strong resistance to tension. The modified curvilinear shape prevents the joint activity from being restricted, with visually concealed scars. It is particularly applicable for repairing large wounds and defects around joints.

Effect of intraocular anti-VEGF on cystoid macular edema associated with Henoch-Schonlein purpura-a case report.

BACKGROUND: To report a bilateral cystoid macular edema associated with Henoch-Schonleinpurpura. CASE PRESENTATION: A 21-year-old man presented a bilateral, painless, and bilateral blurred vision for 5 weeks with visual acuity (VA) of 6/12 on the right eye and 6/48 on the left. FA and OCT showed bilateral cystoid macular edema, and the fundus photograph showed retinal hemorrhages. Using intravenous dexamethasone could reduce macular edema, but it reoccurred shortly after switching to oral prednisone. Repeated intraocular injection of anti-VEGF in both eyes was performed and VA improved to 6/6 on the right eye and 6/7.5 on the left with the regression of edema after 6 months follow-up. CONCLUSIONS: Intraocular anti-VEGF might be an alternative choice to glucocorticoid in cases of bilateral cystoid macular edema associated with Henoch-Schonlein purpura.

The mechanism of the preventive effect of Shen'an capsule on the calcium oxalate crystal-induced early renal injury based on metabolomics.

Kidney stone disease is a worldwide metabolism-associated disorder with a high incidence of renal dysfunction. However, effective methods to prevent crystalline nephropathy are still lacking owing to the absence of aetiological research. Shen'an (SA) capsules are prepared from Chinese medicinal compounds and are considered a promising treatment for the prevention of crystal-induced renal injury. In this study, 24 mice were randomly divided into four groups: saline, oxalate, SA-treated (via preventive administration) and SA-only groups. A metabolomics analysis based on ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS) was performed to explore the plasma metabolic profiles among the different groups. The amount of crystal deposition and the decline in kidney function were significantly alleviated by the use of SA capsule. A total of 24 metabolites that showed a reversal trend following SA capsule administration were identified as plasma biomarkerss of the preventive effects of SA capsules on crystal-induced renal injury. Most of these metabolites were involved in the metabolisms of lipid metabolism, energy metabolism, glutathione metabolism and vitamin metabolism. In conclusion, SA capsules exert a preventive effect in mice with crystal-induced kidney injury via the regulation of multiple metabolic pathways.

Repeat Surgery after Percutaneous Endoscopic Lumbar Discectomy for Adolescent Lumbar Disc Herniation: A Multicenter Observational Study.

OBJECTIVE: The reported date in the repeat surgical intervention for adolescent lumbar disc herniation (ALDH) after percutaneous endoscopic lumbar discectomy (PELD) was quite scarce. This study aims to introduce cases of repeat surgeries after PELD for ALDH and assess the incidence, chief causes, repeat surgery methods, and surgical outcomes of repeat surgeries after PELD for ALDH. METHODS: A retrospective multicenter observational study was conducted on patients undergoing repeat surgeries after PELD for ALDH at four tertiary referral hospitals from January 2014 through August 2022. The incidence of repeat surgeries, chief causes, strategies for repeat surgeries, and timing of repeat surgeries were recorded and analyzed. The clinical outcomes were evaluated by the Numeric Rating Scales (NRS) scores and the modified MacNab criteria. Statistical analyses were performed with the Wilcoxon signed-rank test. RESULTS: A total of 23 patients who underwent repeat surgeries after PELD for ALDH were included. The chief causes were re-herniation (homo-lateral re-herniation at the same level, new disc herniation of adjacent level). The repeat surgery methods were revision PELD, micro-endoscopic discectomy (MED), open discectomy and instrumented lumbar inter-body fusion. The NRS scores decreased significantly in follow-up evaluations and these scores demonstrated significant improvement at the last follow-up (p < 0.002). For the modified MacNab criteria, at the last follow-up, 18 patients (78.26%) had an excellent outcome, and the overall success rate was 86.95%. CONCLUSION: This study's data suggest that young patients who underwent repeat surgery improved significantly compared to baseline. The chief cause was re-herniation. Revision PELD was the main surgical procedure, which provides satisfactory clinical results in young patients who underwent repeat surgeries.

Exosomes incorporated with black phosphorus quantum dots attenuate retinal angiogenesis via disrupting glucose metabolism.

Black phosphorus quantum dots (BPQDs) have shown potential in tumor therapy, however, their anti-angiogenic functions have not been studied. Although BPQDs are easily degraded to non-toxic phosphrous, the reported toxicity, poor stability, and non-selectivity largely limit their further application in medicine. In this study, a vascular targeting, biocompatible, and cell metabolism-disrupting nanoplatform is engineered by incorporating BPQDs into exosomes modified with the Arg-Gly-Asp (RGD) peptide (BPQDs@RGD-EXO nanospheres, BREs). BREs inhibit endothelial cells (ECs) proliferation, migration, tube formation, and sprouting in vitro. The anti-angiogenic role of BREs in vivo is evaluated using mouse retinal vascular development model and oxygen-induced retinopathy model. Combined RNA-seq and metabolomic analysis reveal that BREs disrupt glucose metabolism, which is further confirmed by evaluating metabolites, ATP production and the c-MYC/Hexokinase 2 pathway. These BREs are promising anti-angiogenic platforms for the treatment of pathological retinal angiogenesis with minimal side effects.

WZY-321 triggers glioma cell apoptosis via XAF1 up-regulation caused by MTM-mediated miR-873 down-regulation.

Gliomas account for the majority of primary malignant brain tumors around the world and are highly aggressive. Evodiamine is one of the main effective components of Evodia rutaecarpa, which can inhibit proliferation and promote apoptosis of tumor cells including glioma cells. The derivative of Evodiamine named WZY-321 was successfully developed, and exhibited significant cytotoxicity and could efficiently induce glioma cell apoptosis; however, the mechanism of WZY-321-induced glioma cell apoptosis is not clear. Our current studies showed that WZY-321 increased X-linked inhibitor of apoptosis-associated factor 1 (XAF1) expression in glioma cells, and up-regulated XAF1 resulted in glioma cell apoptosis. Moreover, WZY-321 treatment decreased miR-873 expression and increased lncRNA MTM expression in glioma cells, and down-regulated miR-873 or up-regulated MTM lead to glioma cell apoptosis. Mechanically, WZY-321 up-regulated XAF1 gene expression via MTM-decreased miR-873 expression, that bound to XAF1 3' UTR and decreased XAF1 mRNA levels. Taken together, these data indicate that WZY-321 triggers glioma cell apoptosis via XAF1 up-regulation caused by MTM-mediated miR-873 down-regulation.

Role of glucose metabolism in ocular angiogenesis (Review).

Glucose metabolism, the major source of energy, plays a crucial role in physiological cell function and the maintenance of homeostasis. Glucose acts as the predominant source of metabolic fuel in the generation of ATP and is involved in biosynthesis and epigenetics. Thus, glucose metabolism maintains a key role in cell function, homeostasis, energy generation, biosynthesis and epigenetics. An increasing number of studies have revealed that glucose metabolism is intricately involved in angiogenesis, with the disruption of angiogenesis contributing to several vascular diseases. Ocular vascular diseases are common ophthalmological disorders, and the prevalence of these disorders is increasing annually. Ocular vascular diseases largely occur from abnormal congenital development or acquired disturbances to the vasculature. Thus, identifying the process of occurrence and development of physiological and pathological angiogenesis is of utmost importance, and this involves understanding the inseparable role of intercellular communications between vascular cells. Although vascular endothelial growth factor (VEGF) is a well­recognized therapeutic target for the management of ocular vascular diseases, VEGF­based therapy fails to achieve the desired therapeutic effects in several cases, partly due to drug resistance and non­compliance. In the present review, current knowledge on the processes and roles of glucose metabolism in governing both physiological and pathological ocular angiogenesis are summarized, highlighting vascular glucose metabolism as a promising strategy for maintaining or restoring the physiological functions of the vasculature, thus potentially ameliorating ocular vascular diseases.

Heterogeneous nuclear ribonucleoprotein A1 exerts protective role in intracerebral hemorrhage-induced secondary brain injury in rats.

Heterogeneous nuclear ribonucleoprotein A1 (hnRNPA1) is the most abundant and expressed widely member of the hnRNP family. It has been extensively studied in developmental biology, oncology, and neurodegenerative diseases, which has not been reported on in intracerebral hemorrhage (ICH) induced-secondary brain injury (SBI). The purpose of this study was to explore the role of hnRNPA1 exerts and its underlying mechanism in ICH-induced SBI. Experimental ICH models were established by injecting autologous heart blood into the basal ganglia region of rats and increased or inhibited hnRNPA1 expression through the hnRNPA1 plasmid and small interfering RNA. The results illustrated that the protein levels of hnRNPA1 are significantly elevated after ICH, and hnRNPA1 is transported from the nucleus to the cytoplasm. Upregulated hnRNPA1 could improve neurological function and the learning and memory ability decline after ICH-induced injury. Furthermore, TUNEL and FJB staining indicated that hnRNPA1 overexpression could reduce neuronal cell death and injury induced by ICH. However, downregulated hnRNPA1 damages neurological function and learning and memory abilities and aggravates neuronal cell degeneration and apoptosis. Consistently, the levels of Bcl-xl mRNA and Bcl-xl are elevated or decreased depending on the levels of hnRNPA1, which could be one of the mechanisms through which hnRNPA1 participates in ICH-induced neuronal cell death. In summary, hnRNPA1 plays a protective role in ICH-induced SBI via upregulating Bcl-xl expression, indicating that hnRNPA1 could be a potential target for ICH therapy.

Anatomical study of the extraocular check ligament system.

AIM: To clarify the gross anatomy structure of the check ligament of the palpebra superior in relation to congenital blepharoptosis operation. METHOD: Seven fixed and three fresh cadavers of Chinese adults (between 53 and 76 years old; 5 males and 5 females) were used. Gross dissection was performed on fourteen eyes in seven cadavers. In three fixed cadavers, six bulbus oculi received histological sections for immunohistochemical tests. RESULT: Below the levator upon the superior rectus, the check ligament described by Lockwood is found. It extends bilaterally and attaches to the orbital wall behind the inner and lateral canthus tendon. Between the inferior obliquus and the inferior rectus, we also found a sheath structure similar to the check ligament extending bilaterally to the orbital wall. These two structures form an annular fascial system surrounding the eyeball. The medial half of the fascial sheath is tenacious, and the immunohistochemical test proves that smooth muscle cells are found in this part. CONCLUSION: We call this whole fascial sheath surrounding the circumocular muscle the Extraocular Check Ligament System (ECLS), and it plays a restricting and checking role in the movement of the eyeball. Surgeons should be aware of the ECLS when performing ptosis or other blepharal surgery.

Double eyelid surgery by using palpebral marginal incision technique in Asians.

BACKGROUND: Approximately 50% of Asians do not have upper eyelid creases. Full-incision methods may leave obvious scars and buried-suture methods cannot remove excess tissues to create a double eyelid. The new palpebral marginal incision technique masked the incision at the upper palpebral margin and removed the excess tissue, thereby achieving scarless and natural double eyelids. METHODS: The modified technique involved the incision site and positioning processes. The incision line is 1.0-1.5 mm above the palpebral margin. A strip of orbicularis muscle beneath the positioned double eyelid must be removed. The orbital septum is then exposed, and a certain amount of orbital fat is removed. Next, the dermis and tarsal plate are sutured in an orderly manner. Finally, a strip of the redundant skin located approximately 1-3 mm above the incision is excised to correct blepharochalasis before the skin is closed. RESULTS: This new technique was performed in 212 patients including 56 patients with blepharochalasis who had their skin excised during the surgery. The follow-up period ranged from 6 months to 3 years. Ninety-five percent of the patients rated excellent and good and that they were satisfied with their surgery, and no significant complications occurred. CONCLUSIONS: The following are the advantages of the authors' technique: (1) minimal or even no surgical scarring is discernible on the eyelids even when they are closed; (2) solves the problem of excessive tissue and correct blepharochalasis; and (3) the double eyelid fold is stable and natural for a long time.