[Clinical characteristics and research progress of ocular Merkel cell carcinoma].

Merkel cell carcinoma (MCC) is a rare, aggressive epithelial and neuroendocrine tumor. MCC typically presents as painless nodules or patches rapidly growing in sun-exposed skin areas. Ocular MCC accounts for approximately 2.5% of all cases and may be misdiagnosed as granuloma or basal cell carcinoma. Risk factors for development include advanced age, ultraviolet exposure, male gender, immunosuppression, and Merkel cell polyomavirus infection. Treatment involves wide local excision with adjuvant radiotherapy, chemotherapy is typically reserved for metastatic disease, and immunotherapy and targeted therapy are currently under investigation showing promising early outcomes. This article summarizes the clinical characteristics and research progress of ocular MCC.

[Misconceptions in diagnosis and treatment of papilledema caused by idiopathic intracranial hypertension].

Papilledema refers to the swelling of the optic disk due to increased intracranial pressure. In clinical practice, papilledema is often confused with optic disc edema. Idiopathic intracranial hypertension (IIH) is a major cause of papilledema and there are still misconceptions about the etiology of IIH, the classification and examination of papilledema, and the treatment of IIH. This article elaborates on the misunderstandings that may exist in the diagnosis and treatment of papilledema, in order to lay a foundation for the standardized diagnosis and treatment of papilledema in China.

[Research progress on the relationship between peripapillary hyper-reflective ovoid mass-like structure and optic nerve diseases].

Peripapillary hyper-reflective ovoid mass-like structure (PHOMS) is a newly discovered optical coherence tomography (OCT) sign of optic disc in recent years, which can be presented in a variety of optic nerve diseases. At present, the OCT structural characteristics and pathological manifestations of PHOMS have been initially understood. This paper summarizes the related literature published recently. The relationship and the latest research progress between PHOMS and some optic neuropathy were mainly focused, hoping to further deepen the understanding and facilitate its wider clinical application.

[Application and research progress of optical coherence tomography angiography in central nervous system diseases].

Optical coherence tomography angiography (OCTA) is a new vascular imaging technology based on high-resolution optical coherence tomography image analysis. It can scan the moving red blood cells in blood vessels for three-dimensional imaging of human retinal and choroidal vessels. Since the close connection of vascular endothelial cells of the blood-retinal barrier is similar to that of the blood-brain barrier, the role of OCTA in the research of pathogenesis and course monitoring of a variety of central system diseases such as Alzheimer's disease, Parkinson's disease, stroke, migraine, multiple sclerosis and optic neuromyelitis has been widely discussed. This article reviews the application and progress of OCTA in central nervous system diseases.

[Prospects and reflections on the research and development of next-generation malaria vaccines].

Vaccination is one of the most effective intervention for the containment and elimination of infectious diseases. Recently, the world's first malaria vaccine RTS, S/AS01 was approved by WHO for use among children living in moderately and highly malaria endemic areas of Africa, which brings a hope for the research and development of malaria vaccines. Here, we review the current status of malaria vaccines development and provide a perspective on the development of next-generation malaria vaccines, so as to provide insights into the successful development of malaria vaccines.

[Clinical characteristics and research progress on the treatment of mitochondrial optic neuropathy].

Mitochondrial optic neuropathy (MON) describes a group of optic neuropathies that exhibit mitochondrial dysfunction in retinal ganglion cells. Pathogenesis of MON includes genetic factors, such as Leber hereditary optic neuropathy and dominant optic atrophy, or acquired factors, such as drug intoxication and nutritional deficiencies, or the combination of both genetic factors and acquired factors. Regardless of different causes, MON shares similar features including bilateral central visual acuity loss, equally normal or slightly sluggish reaction of pupils to light and so on. Many novel therapies, such as pharmacological strategies, genetic therapy and stem cell therapy, are being widely studied in order to limit or reverse the damage of retinal ganglion cells. This article review the pathogenesis, clinical manifestations, ancillary testing, differential diagnosis and treatment progress of MON. (Chin J Ophthalmol, 2021, 57: 386-390).

[Effects of intravenous methylprednisolone pulse therapy on recurrent optic neuritis associated with aquaporin 4 antibody seropositive neuromyelitis optica].

Objective: To observe the effects of intravenous methylprednisolone pulse (IVMP) therapy on the recovery of visual acuity and its influencing factors in patients with the relapse of aquaporin (AQP) 4 antibody positive neuromyelitis optica related optic neuritis (NMO-ON). Methods: Retrospective case series. Forty-eight eyes of 35 patients diagnosed as NMO-ON in the Neuro-ophthalmology Clinic of Beijing Tongren Hospital from September 2012 to April 2018 were included in this research. All patients were AQP4 antibody seropositive, and had clinical manifestations of acute optic neuritis, with a history of optic neuritis treated with glucocorticoids effectively. They received the treatment of IVMP 500 mg/d or 1 000 mg/d for 3 to 5 days. The post-treatment and pre-treatment visual acuities were compared. Improving four lines or more was considered as markedly effective, improving two or three lines as effective, and improving one line or no change or a decline as no effect. The impacts of age, visual acuity at onset, relapse rate and dosage on the acute exacerbation of NMO-ON were analyzed. Mann-Whitney U test and Kruskal-Wallis test were used for statistical analysis. Results: Among the 35 patients, there were 2 males and 33 females, aged from 15 to 73 years (median, 36 years). In the 48 eyes of recurrence, the treatment was effective 41.7% (20/48), effective 20.8% (10/48), and ineffective 37.5% (18/48). The IVMP therapy was effective in 25 of 34 eyes with one recurrence and 5 of 14 eyes with two or more recurrences, and the difference was statistically significant (Z=2.315, P=0.021). The efficacy in 13 eyes with preoperative visual acuity not lower than 0.05 (10/13) was better than 35 eyes with preoperative visual acuity lower than 0.05 (20/35), and the difference was statistically significant (Z=1.994, P=0.046). Different ages and doses (1 000 mg/d and 500 mg/d) made no significant difference in the efficacy (P=0.273,0.105). Conclusions: The IVMP therapy is effective for the NMO-ON relapse in patients who were AQP4 antibody seropositive. The effect of IVMP treatment at doses of 500 mg/d and 1 000 mg/d is similar. Furthermore, visual acuity less than 0.05 and more relapses reduce the efficacy in relapsed NMO-ON patients. (Chin J Ophthalmol, 2020, 56: 509-513).

[Effects of intravenous methylprednisolone pulse therapy on optic neuritis associated with AQP4 antibody seropositive neuromyelitis optica].

Objective: To observe the effect of intravenous methylprednisolone pulse (IVMP) therapy on the recovery of visual acuity and its influencing factors in patients with the first attack of optic neuritis associated with aquaporin-4(AQP4) antibody seropositive neuromyelitis optica. Methods: Retrospective case series study. A total of 165 eyes of 120 patients diagnosed as optic neuritis related to neuromyelitis optica for the first time in the Neuro-ophthalmology Clinic of Beijing Tongren Hospital from September 2012 to December 2017 were selected in this research. All patients had AQP4 antibody seropositivity and clinical manifestations of acute optic neuritis, excluding other diagnoses. All the patients received the treatment of IVMP 500 mg/d or 1 000 mg/d for 3 days, followed by a slowly tapering course of oral glucocorticoids. The post-treatment and pre-treatment visual acuities were compared. Improving four lines or more was considered as effective markedly, improving two or three lines as effective, and improving one line or no change or a decline as no effect. The onset age, visual acuity before treatment and doses in the acute exacerbation were analyzed. The Mann-Whitney U test and Kruskal-Wallis test were used for statistical analyses. Results: Among the 120 patients, there were 17 males and 103 females, with age ranging from 16 to 80 years (median, 44 years). There were 17.6% (29/165) of the eyes with conspicuous therapy, 33.3% (55/165) of the eyes with effective therapy and 49.1% (81/165) of the eyes with ineffective therapy. The effect of IVMP decreased obviously when the age of onset was over 50 years old [41.1%(23/56) vs. 56.0%(61/109), Z=2.645, P=0.008]. Patients with no light perception and light perception before treatment had better therapeutic effect than those with counting fingers-0.3 before treatment [72.2%(26/36), 72.7%(24/33) vs. 30.1%(25/83), Z=2.726, 2.967; P=0.006, 0.003]. Although the efficacy of patients with visual acuity of onset over 0.3 (9/13) was better than patients with counting fingers-0.3, but the difference was not statistically significant (Z=1.743, P=0.081). Different doses, including IVMP 1 000 mg/d and 500 mg/d, had no significant difference in the effect (Z=1.115, P=0.265). Conclusions: IVMP therapy is only valid for a half of eyes with optic neuritis associated with AQP4 antibody seropositive neuromyelitis optica. The effect of IVMP treatment at doses of 500 mg/d and 1 000 mg/d is similar. Furthermore, the visual acuity from finger counting to 0.3 and age of onset over 50 years old have an influence on the treatment effect. (Chin J Ophthalmol, 2019, 55: 180-185).

[The progress of research on the immune pathogenesis and biomarkers in optic neuritis related to neuromyelitis optica].

The idiopathic optic neuritis (ION) which is related to neuromyelitis optica (NMO) and neuromyelitis optica spectrum disorders (NMOSD) is called optic neuritis related to neuromyelitis optica (NMO-ON). Because of the high rates of blindness, disability and fatality of NMO, the heterogeneous clinical presentation, severity of neurologic disability following relapses, and variability of therapeutic responses, reliable and sensitive biomarkers for onset, relapse, and progression in NMO are urgently needed. Currently, detecting aquaporin-4 (AQP4) antibodies (AQP4-IgG or NMO-IgG) in serum is employed as the major supporting approach for the diagnosis of seropositive NMO, however, AQP4-IgG seronegativity in 10% to 25% of NMO patients suggests that there are several other factors involved in NMO immunopathogenesis. Collaborative international studies hold great promise for establishing and validating biomarkers of NMO. This article discusses known and potential biomarkers for NMO. The biomarkers of NMO maybe the potential biomarkers of NMO-ON, for ION is the initial presentation and the earliest stage. (Chin J Ophthalmol, 2019, 55:228-233).

Bone marrow stem cells-derived exosomes extracted from osteoporosis patients inhibit osteogenesis via microRNA-21/SMAD7.

OBJECTIVE: To explore whether bone marrow stem cells (MSCs)-derived exosomes extracted from osteoporosis patients could inhibit osteogenesis via microRNA-21/SMAD7. PATIENTS AND METHODS: MSCs from osteoporosis patients were isolated and cultured. MSCs morphology was observed, and the specific surface antigens were identified by flow cytometry. The osteogenic ability of MSCs was detected by alizarin red staining and oil red staining. Exosomes were collected from MSCs suspension by ultracentrifugation, and microRNA-21 expression in MSCs derived-exosomes was detected. Moreover, protein and mRNA levels of ALP, Bglap, and Runx2 in MSCs treated with different sources of MSCs-derived exosomes were detected by qRT-PCR (quantitative real-time polymerase chain reaction) and Western blot, respectively. ALP activity in MSCs was accessed by a relative commercial kit. Furthermore, binding sites of microRNA-21 and SMAD7 were predicted by Targetscan, miRWalk, and miRDB, and were further verified by luciferase reporter gene assay. SMAD7 expression in MSCs derived-exosomes was also detected. RESULTS: MSCs extracted from healthy adults, and osteoporosis patients were in adherent growth and exhibited elongated morphology, which could differentiate into osteoblasts and lipoblasts after different inductions. MicroRNA-21 expression in MSCs-derived exosomes extracted from osteoporosis patients was remarkably higher than those extracted from healthy adults. Decreased Runx2 expression and ALP activity were found after treatment of MSCs-derived exosomes extracted from osteoporosis patients. SMAD7 was confirmed to bind to microRNA-21 and was downregulated in osteoporosis patients in comparison with healthy adults. Overexpression of SMAD7 resulted in downregulated ALP, Bglap, and Runx2. CONCLUSIONS: MicroRNA-21 inhibits osteogenesis through regulating MSCs-derived exosomes extracted from osteoporosis patients via targeting SMAD7.

Shape-memory collagen scaffold for enhanced cartilage regeneration: native collagen versus denatured collagen.

OBJECTIVE: Nowadays, it is still questionable whether denatured collagen (DCol) can replace the native collagen (Col) as a bioactive protein in cartilage engineering. We sought to study the advantages of Col with a triple-helical structure in the collagen-based composite materials for cartilage engineering. METHODS: We presented new three-dimensional (3D) Col and DCol scaffolds with shape memory properties. The effects of Col and DCol scaffolds on rabbit chondrocytes' proliferation, adhesion, differentiation and interaction with matrix were investigated. Tissue compatibility was performed in a subcutaneous Sprague Dawley (SD) rat model. The repair ability of different scaffolds with chondrocytes for full-thickness articular cartilage defects in knee joints of New Zealand white rabbits were investigated. RESULTS: The results indicated that the Col scaffolds (with concentration 1.6wt% and 0.8wt%, respectively) promoted the proliferation, adhesion and redifferentiation of chondrocytes, as well as chondrocyte-matrix interaction, to a greater degree than the DCol scaffolds. In the animal experiment, the Col scaffolds filled in the defect hole significantly maintained chondrocytes function, promoted cartilage and subchondral bone regeneration, compared with the DCol scaffolds, and the scaffolds loaded with chondrocytes were better than the cell-free scaffolds, especially in the case of the Col scaffolds (1.6 wt%). CONCLUSIONS: Taken together, these insights suggest that the better proliferation, adhesion and redifferentiation of chondrocytes in Col scaffolds with the triple-helical structure may contribute to the greater cartilage repair ability. Col scaffolds may be more appropriate for repairing cartilage defects than DCol scaffolds, and DCol cannot as an alternative when using collagen-based materials for cartilage engineering applications.

TIGAR mediates the inhibitory role of hypoxia on ROS production and apoptosis in rat nucleus pulposus cells.

OBJECTIVE: Hypoxia has been shown to inhibit reactive oxygen species (ROS) production in nucleus pulposus (NP) cells. The TP53-induced glycolysis and apoptosis regulator (TIGAR) has been reported to suppress oxidative stress. We sought to explore the role of TIGAR in the effect of hypoxia on ROS production and apoptosis. METHODS: An intervertebral disc degeneration (IDD) model of Sprague-Dawley (SD) rat caudal spine was established by puncturing the Co6-7 disc. TIGAR expression was detected by immunohistochemistry and western blotting in human and SD rat NP tissues of degenerated discs. Rat primary NP cells treated with hypoxia and cobalt chloride (CoCl2) were analyzed by western blotting for TIGAR expression. After TIGAR silence with TIGAR siRNA transfection, apoptosis percentage, mitochondrial and total intracellular ROS levels were measured. H2O2 was used to further check the effects of TIGAR on oxidative stress. Finally, NADPH/NADP+ and GSH/GSSH ratio were examined after TIGAR silencing under hypoxic conditions and after H2O2 treatment. RESULTS: A degree-dependent increase in TIGAR expression was observed in human and rat degenerated NP tissues. Hypoxia and hypoxia-inducer CoCl2 enhanced TIGAR and P53 expressions in rat NP cells. TIGAR silence reversed the inhibitory effects of hypoxia on intracellular and mitochondrial ROS production, as well as apoptosis percentage. However, TIGAR silence aggravated H2O2-induced ROS production. In addition, TIGAR increased NADPH/NADP+ and GSH/GSSH ratio in NP cells. CONCLUSIONS: These results suggested that TIGAR appears to mediate the protective role of hypoxia on ROS production and apoptosis percentage by enhancing NADPH/NADP+ and GSH/GSSH ratio.

Heat shock proteins and survivin: relationship and effects on proliferation index of retinoblastoma cells.

Survivin and HSPs (heat shock proteins) are important anti-apoptotic proteins. However, limited research has been done regarding the collective effects of HSPs and survivin on the proliferative activities of RB cells. The purpose of this study was to narrow this gap by focusing on the expression of HSP70 and HSP90 and the interaction of these proteins with survivin. The proliferative activities of RB cells were analyzed by assessing the Ki-67 labeling index. Ki-67 recognizes a nuclear antigen expressed in all phases of the cell cycle except G(0) and early G(1), which makes it an excellent marker of cells in the proliferative phase. Immunohistochemical procedures were performed on retinal tissues from 43 RB patients who had undergone enucleation. Expression of HSP70, HSP90 and survivin was found in 65.12%, 86.05% and 62.79% of the cases respectively. No expression of any of these markers was found in normal retinal tissues. Expression of survivin was more frequent when HSP90 was detected than when HSP90 was not detected (P<0.05). The Ki-67 labeling index was higher in cases in which HSP90 or survivin was found than in cases in which neither protein was found (P<0.05). The Ki-67 labeling index was higher in cases positive for both HSP90 and survivin than in cases in which neither protein or only one protein was found (P<0.05). Expression of HSP70 neither correlated with that of survivin, nor had any significant effect on the Ki-67 labeling index (P>0.05). Although expression of HSPs and survivin and the Ki-67 labeling index did not correlate with histopathologic typing of RB (P>0.05), our findings demonstrate that expression of HSP90 correlates with that of survivin in RB and the co-existence of survivin and HSP90 probably plays an important role in cellular proliferation in RB. Further work is indicated to clarify the role of these processes in progression of RB.