Clinicopathological Characteristics of Three Cases with Recurrent Orbital Solitary Fibrous Tumors: A Retrospective Study and Literature Review.

Objective: Solitary fibrous tumor (SFT) is a spindle cell neoplasm that rarely occurs in orbit. This study aimed to report the clinical, imaging, and pathological features of three patients with recurrent orbital SFTs. Methods: Clinical, imaging, and pathological data of the three patients were retrospectively reviewed, and the results were compared with those of previously reported cases with recurrent orbital SFT. Results: One female and two male patients (mean age, 54 years old) were included in this study. The present cases and literature review showed that the average time to recurrence in patients who aged under 50 years old was shorter than that in those who aged over 50 years old. The most common site for recurrent orbital SFT was the retrobulbar area of the orbit (23.8%). Imaging examinations showed consistent intensity of MRI signals before and after recurrence. Immunohistochemical results of all cases revealed the expressions of CD34. The mitotic rate increased in 4/8 cases, and the percentage of Ki-67-positive cells was elevated in 5/16 cases. Conclusion: These results suggested that young patients were more likely subjected to recurrent orbital SFT. The postoperative pathological diagnosis revealed that patients with recurrent orbital SFT had more nuclear abnormalities and mitotic activity, as well as a higher percentage of Ki-67-positive cells, indicating that orbital recurrent SFT tended to be malignant according to both morphological features and immunohistochemistry results.

Mechanistic insights into the alterations and regulation of the AKT signaling pathway in diabetic retinopathy.

In the early stages of diabetic retinopathy (DR), diabetes-related hyperglycemia directly inhibits the AKT signaling pathway by increasing oxidative stress or inhibiting growth factor expression, which leads to retinal cell apoptosis, nerve proliferation and fundus microvascular disease. However, due to compensatory vascular hyperplasia in the late stage of DR, the vascular endothelial growth factor (VEGF)/phosphatidylinositol 3 kinase (PI3K)/AKT cascade is activated, resulting in opposite levels of AKT regulation compared with the early stage. Studies have shown that many factors, including insulin, insulin-like growth factor-1 (IGF-1), VEGF and others, can regulate the AKT pathway. Disruption of the insulin pathway decreases AKT activation. IGF-1 downregulation decreases the activation of AKT in DR, which abrogates the neuroprotective effect, upregulates VEGF expression and thus induces neovascularization. Although inhibiting VEGF is the main treatment for neovascularization in DR, excessive inhibition may lead to apoptosis in inner retinal neurons. AKT pathway substrates, including mammalian target of rapamycin (mTOR), forkhead box O (FOXO), glycogen synthase kinase-3 (GSK-3)/nuclear factor erythroid 2-related factor 2 (Nrf2), and nuclear factor kappa-B (NF-κB), are a research focus. mTOR inhibitors can delay or prevent retinal microangiopathy, whereas low mTOR activity can decrease retinal protein synthesis. Inactivated AKT fails to inhibit FOXO and thus causes apoptosis. The GSK-3/Nrf2 cascade regulates oxidation and inflammation in DR. NF-κB is activated in diabetic retinas and is involved in inflammation and apoptosis. Many pathways or vital activities, such as the Janus kinase (JAK)/signal transducer and activator of transcription (STAT) and mitogen-activated protein kinase (MAPK) signaling pathways, interact with the AKT pathway to influence DR development. Numerous regulatory methods can simultaneously impact the AKT pathway and other pathways, and it is essential to consider both the connections and interactions between these pathways. In this review, we summarize changes in the AKT signaling pathway in DR and targeted drugs based on these potential sites.

The mTOR signalling in corneal diseases: A recent update.

Corneal diseases affect 4.2 million people worldwide and are a leading cause of vision impairment and blindness. Current treatments for corneal diseases, such as antibiotics, steroids, and surgical interventions, have numerous disadvantages and challenges. Thus, there is an urgent need for more effective therapies. Although the pathogenesis of corneal diseases is not fully understood, it is known that injury caused by various stresses and postinjury healing, such as epithelial renewal, inflammation, stromal fibrosis, and neovascularization, are highly involved. Mammalian target of rapamycin (mTOR) is a key regulator of cell growth, metabolism, and the immune response. Recent studies have revealed that activation of mTOR signalling extensively contributes to the pathogenesis of various corneal diseases, and inhibition of mTOR with rapamycin achieves promising outcomes, supporting the potential of mTOR as a therapeutic target. In this review, we detail the function of mTOR in corneal diseases and how these characteristics contribute to disease treatment using mTOR-targeted drugs.

Virtual reality training improves accommodative facility and accommodative range.

AIM: To evaluate the effects of virtual reality (VR) training on different parameters of vision. METHODS: Sixty individuals ranged 18-60 years old with asthenopia were randomly divided into short-term (n=40) and long-term (n=20) treatment groups. They were given a specially designed VR training device only once for 15min or 3-4 times a day for 15min each time for 1mo. The visual acuity, spherical equivalent, accommodative range, accommodative facility, pupil size, and visual fatigue were evaluated before (control) and after VR training. RESULTS: The visual acuity, accommodative range, and accommodative facility increased in subjects of the short-term treatment group, whereas their pupil size contracted significantly. No significant changes in spherical equivalent and visual fatigue were observed. The changes in distant vision and corrected visual acuity were positively correlated with those in pupil size, but not with spherical equivalent. The accommodative range and accommodative facility improved significantly in subjects of the long-term treatment group. No significant changes in visual acuity, spherical equivalent, pupil size, and visual fatigue were noted. CONCLUSION: VR training can improve the accommodative range and accommodative facility of human eyes. Although short-term VR training can transiently improve vision, which probably due to bright light adaptation, there is no evidence that it can improve myopia.

Preoperative transarterial embolization of a recurrent orbital solitary fibrous tumor with significant hypervascularity: a case report.

BACKGROUND: Orbital solitary fibrous tumors (SFTs) are rare neoplasms. Recurrent, hypervascular, malignant variations of orbital SFTs have recently been noted and can present a surgical challenge. CASE PRESENTATION: We describe a case of a 53-year-old Chinese woman with a history of a resected orbital SFT. She presented with proptosis, limited eyeball movement, and visual loss in the right eye, suggestive of a recurrent SFT. Ocular examination with multimodal imaging revealed a large, nonpulsatile, noncompressible, hypervascular mass behind the eyeball. The patient underwent preoperative transarterial embolization of the main blood supply to the tumor in order to control intraoperative blood loss, followed by ocular enucleation to optimize exposure and enable complete resection of the tumor. Embolization of the right ophthalmic artery and the distal branch of the right internal maxillary artery caused an immediate, substantial reduction of vascular flow, which allowed us to enucleate the eyeball and resect the tumor with minimal blood loss and no complications. CONCLUSIONS: Our case is so far the first Chinese case of successful preoperative embolization of the main blood supply to a large, recurrent, hypervascular orbital SFT. This case also described a different surgical approach to achieve total removal of an orbital SFT without osteotomy.

Investigation of dry eye symptoms of medical staffs working in hospital during 2019 novel coronavirus outbreak.

The aim of this study was to survey the prevalence of dry eye symptoms (DES) among doctors and nurses in the period of 2019, novel coronavirus (COVID-19) outbreak.To evaluate the DES of doctors and nurses worked at front-line hospitals with protective glasses for a mean time of 4 to 6 hours, a questionnaire developed by the researchers with the Ocular Surface Disease Index (OSDI) was used. These data were evaluated using descriptive statistics and correlation test with SPSS 22.0.The study included 13 doctors and 40 nurses, among which 16 were male and 37 were female, and the mean age of the participants was 32.43 ±â€Š5.15 years old. According to the OSDI scores, 64.15, 24.52, 7.54, and 3.77% of the participants experienced occasional, mild, moderate, and severe DES, respectively. The factors significantly correlated with OSDI scores were age and duration of wearing protective glasses, while the duration of wearing protective glasses may be a protective factor of dry eye symptoms.Our study showed that most of the doctors and nurses worked at the front-line of combating COVID-19 did not experience DES, while the symptoms of those who experienced DES might be improved by wearing protective glasses.

Recent developments in regenerative ophthalmology.

Regenerative medicine (RM) is one of the most promising disciplines for advancements in modern medicine, and regenerative ophthalmology (RO) is one of the most active fields of regenerative medicine. This review aims to provide an overview of regenerative ophthalmology, including the range of tools and materials being used, and to describe its application in ophthalmologic subspecialties, with the exception of surgical implantation of artificial tissues or organs (e.g., contact lens, artificial cornea, intraocular lens, artificial retina, and bionic eyes) due to space limitations. In addition, current challenges and limitations of regenerative ophthalmology are discussed and future directions are highlighted.

The Effects of Consumer-grade Virtual Reality Headsets on Adult Visual Function.

INTRODUCTION: Consumer-grade virtual reality (VR) headset is being used with increasing frequency nowadays, however, the effect on visual function is not clear. OBJECTIVES: We here investigate whether using VR headset changes adults' visual function and take into account the possible factors. METHODS: We compared the uncorrected distant visual acuity (UDVA), uncorrected near visual acuity (UNVA), best corrected visual acuity (BCVA), low contrast visual acuity (LCVA), glare visual acuity (GVA), refractive error (RE), amplitude of accommodation (ACC), and pupil diameter (PD) before and after using VR headset 10 mintues at a time twice per day for 2 successive weeks in 40 volunteers with a mean age of 28.6 years. Differences in these 8 parameters before vs. after VR headset use were analyzed using SPSS 22.0. RESULTS: In our study, we found that the amplitude of accommodation had significantly increased by 0.53 (F = 5.673; P = .006) after using, while visual acuity, refractive error and pupil diameter did not show statistically significant changes (P > .05). Correlation test showed that there was no significant correlation between any two parameters on visual function. CONCLUSION: It is discovered that using a consumer-grade VR headset 10 minutes at a time twice daily for 2 weeks improved the amplitude of accommodation of adults dramatically, while neither visual acuity nor refractive error was affected. ABBREVIATIONS: VR: visual reality; UDVA: uncorrected distant visual acuity; UNVA: uncorrected near visual acuity; BCVA: best corrected visual acuity; LCVA: low contrast visual acuity; GVA: glare visual acuity; RE: refractive error; ACC: amplitude of accommodation; PD: pupil diameter; 3D: three-dimensional; VDTS: visual display terminal syndrome; FOV: field of view; SEQ: spherical equivalent diopter.

Outcomes of 4 surgical adjuvants used for internal limiting membrane peeling in macular hole surgery: a systematic review and network Meta-analysis.

AIM: To compare the outcomes of four adjuvants used for internal limiting membrane (ILM) peeling in macular hole surgery, including indocyanine green (ICG), brilliant blue G (BBG), triamcinolone (TA) and trypan blue (TB), through systematic review and random-effects Bayesian network Meta-analysis. METHODS: PubMed, Cochrane library databases and Web of Science were searched until August 2018 for clinical trials comparing the above four adjuvants. ORs for postoperative best corrected visual acuity (BCVA) improvement and primary macular hole closure rates were compared between the different adjuvants. RESULTS: Twenty-seven eligible articles were included. For postoperative BCVA improvement, results of BBG-assisted peeling were significantly more favorable than those of ICG (WMD 0.08, 95% credible interval 0.01-0.16) and TA ranked highest. No significant differences were found between any other two groups in postoperative BCVA improvement. For postoperative primary macular hole closure rates, BBG ranked highest. However, no significant differences were shown between any two groups. CONCLUSION: TA and BBG are the optimum adjuvants for achieving postoperative BCVA improvement macular hole surgery with adjuvant-assisted ILM peeling. Among all adjuvants, the use of BBG is associated with the highest postoperative macular hole closure rate.

A Branch Point on Differentiation Trajectory is the Bifurcating Event Revealed by Dynamical Network Biomarker Analysis of Single-Cell Data.

The advance in single-cell profiling technologies and the development in computational algorithms provide the opportunity to reconstruct pseudo temporal trajectory with branch point of cellular development. On the other hand, theories such as dynamical network biomarkers (DNB) theory have been recently proposed to characterize the pre-transition state in biological systems. Few studies have validated whether the branch point identified in pseudo time is the critical point in dynamical system. In this study, the dynamical behavior of the branch point on the pseudo trajectory has been investigated. We study the pseudo temporal trajectories reconstructed by Wishbone and diffusion pseudotime analysis (DPT) algorithms, as well as the simulated trajectory. DNB theory is applied to justify the bifurcating event on the pseudo trajectories. Our results demonstrate that the branch point recovered by Wishbone and DPT algorithms is confirmed as a transition state in cell differentiation process by DNB theory. Furthermore, we show that an appropriate DNB group will amplify the comprehensive index of critical event as defined in DNB theory. Our study provides biological insights on pseudo trajectory with branch point in a dynamical view and also indicates that DNB theory may serve as a benchmark to check the validity of branch point.

A Meta-analysis of the association between different genotypes (G11778A, T14484C and G3460A) of Leber hereditary optic neuropathy and visual prognosis.

AIM: To analyze the influences of different genotypes (G11778A, T14484C and G3460A) of Leber hereditary optic neuropathy (LHON) on visual prognosis. METHODS: After a systematic literature search, all relevant studies evaluating the association between the three primary mutations of LHON and visual prognosis were included. All statistical tests were calculated with Revman 5.2 and STATA 12.0. RESULTS: Ten independent studies were included finally. A significant association between the three primary mutations and prognostic vision over 0.3 were found in G11778A versus T14484C [odds ratio (OR)=0.10, 95% confidence interval (CI)=0.05-0.17, P<0.001], G11778A versus G3460A (OR=0.18, 95%CI=0.09-0.37, P<0.001) and T14484C versus G3460A (OR=2.45, 95%CI=1.10-5.48, P<0.05). In addition, obtained by pairwise comparison, the vision during onset, age of onset and sex ratio of these three kinds of patients, have no statistical significance (P>0.05). CONCLUSION: From pairwise comparison, we conclude that these three different genotypes of LHON are related to patients' visual prognosis. The T14484C patients might have a best prognostic vision, G3460A second, and G11778A worst. And there is little relation between the three different genotypes and patients' vision, age of onset and sex ratio.

Production of functional native human interleukin-2 in tobacco chloroplasts.

Interleukin-2 (IL-2) is an important T lymphocyte-derived cytokine in the mammalian immune system. Non-native, recombinant IL-2 derived from Escherichia coli is used widely in both medical research and treatment of diseases. Recombinant human IL-2 gene has been expressed in plant nuclear genomes, therefore it can be spread to the environment through pollen. Furthermore, all the plant-produced IL-2 reported thus far had been attached with artificial tags or fusion proteins, which may trigger unintended immunological responses and therefore compromise its full utility as a medicine. To expand the potential of using plant chloroplasts to produce functional native human therapeutic proteins, we inserted an engineered human interleukin-2 (hIL-2)-coding gene, without any tags, into the chloroplast genome of tobacco (Nicotiana tabacum L.). Partially purified hIL-2 protein from the leaves of the transplastomic plants induced in vitro proliferation of IL-2-dependent murine T lymphocytes. Our study demonstrates that plant chloroplasts can serve as a bio-factory for production of an active native human interleukin in a self-contained and therefore environmentally safe manner.

[Clinical significance of mast cells and IL-9 in B-NHL].

OBJECTIVE: To investigate the role of mast cells and interleukin-9 (IL-9) in B-cell non-Hodgkin lymphoma (B-NHL) development and its clinical significance. METHODS: The expression level of CD117 in tumor tissues of 32 B-NHL patients was determined by Western blot. The infiltration of CD117⁺ mast cells (MCs) in human B-NHL tumor tissues was observed by immunohistochemistry staining. To evaluate the correlations between the data from CD117⁺ MCs and biological markers of human B-NHL, a Spearman correlation coefficient (rs) was calculated. IL-9 levels in sera of B-NHL patients were measured by ELISA. Effects of IL-9 on expressions of functional genes of mouse bone marrow-derived mast cells (BMMCs) were detected by real-time quantitative RT-PCR. RESULTS: The expression of CD117 was upregulated significantly in human B-cell NHL involved tissues when compared with that of controls (0.0551±0.0064 vs 0.0192±0.0072, P<0.01). Infiltration of more CD117⁺ MCs was found in tissues from B-cell NHL subjects compared with that of controls. IL-9 level in serum samples from patients with B-cell NHL was higher than that from healthy controls. Addition of rIL-9 to the culture gave rise to increase in the purity of mouse BMMCs in the first three weeks. In vitro culture experiments showed that the addition of IL-9 could induce the differentiation of mouse BMMC and the expressions of MC-related genes, including CD117, Fcer1α, Mcpt1 and Mcpt5. CONCLUSION: Our study showed that IL-9 promoted immune response mediated by MCs, and probably played important roles in B-NHL growth. Pharmacological or targeted inhibition of mast cells or IL-9 activity may provide new strategy for B-cell NHL therapy.

Is survivin a novel pathway for the treatment and pathogenesis of keloid?

Keloids behave like benign tumors as they grow beyond the boundaries of the original wound margin, do not regress spontaneously, and recur despite treatments. Recently, accumulating evidences showed that survivin played an important role in cell growth, apoptotic resistance, and cell cycle control. More than that, survivin was confirmed to be associated with tumor angiogenesis and chemoresistance. Survivin blocker therapy has been proved to be a novel treatment in some kinds of tumors. Our preliminary work showed that survivin expression was significantly higher in keloids than in normal skin. The mRNA and protein levels of survivin were downregulated in keloid fibroblasts by survivin-siRNA. Therefore, we hypothesize that survivin has a profound effect on keloid formation and progression. Therefore, survivin may be a potential therapeutic target for keloids. Our hypothesis sheds light for the first time on the role of survivin involves in keloid pathophysiology and provides with novel therapeutic implications for keloids that are associated with apoptosis.