Association of aquaporin-4 antibody-seropositive optic neuritis with vision-related quality of life and depression.

Objective: Aquaporin-4 (AQP4) antibody-seropositive optic neuritis (AQP4-ON) is one of the most common types of optic neuritis in China. However, the association between AQP4-ON and vision-related quality of life (QoL) and depression remains poorly understood. Methods: In this cross-sectional study, 57 patients with optic neuritis were evaluated for their vision-related QoL using a Chinese version of the 25-item National Eye Institute Visual Function Questionnaire (VFQ-25) and assessed for depressive symptoms using a Chinese version of the Beck Depression Inventory-II (BDI-II). Data regarding participants' age, sex, visual acuity, and the number of recurrence events were gathered. Linear regression analysis was employed to investigate the relationships between AQP4-ON and vision-related QoL, as well as depression. Results: Of the 57 included patients, 28 were AQP4-ON, and 29 were idiopathic optic neuritis (ION). AQP4-ON demonstrated a significant correlation with a decreased VFQ-25 composite score (Mean difference, -11.65 [95% CI, -21.61 to -1.69]; p = 0.023) and an increased BDI-II score (Mean difference, 6.48 [95% CI, 0.25 to 12.71]; p = 0.042) when compared to ION. The BDI-II score was correlated with the VFQ-25 composite score (Spearman ρ = -0.469; p < 0.001) but not with the visual acuity in the worse-seeing eye (Spearman ρ = 0.024; p = 0.860) or in the better-seeing eye (Spearman ρ = -0.039; p = 0.775), bilateral severe visual impairment (Spearman ρ = 0.039; p = 0.772) or the number of recurrence events (Spearman ρ = 0.184; p = 0.171). Conclusion: AQP4-positive optic neuritis is associated with a decline in vision-related quality of life as well as an increased likelihood of experiencing depression. It is crucial for clinicians to assess both vision-related QoL and depression in patients with AQP4-positive optic neuritis to provide patient-centered care.

Isolation and Genetic Evolution of Dengue Virus from the 2019 Outbreak in Xishuangbanna, Yunnan Province, China.

Background: Dengue virus (DENV) can be divided into four serotypes-DENV-1, DENV-2, DENV-3, and DENV-4. In humans, infection leads to dengue fever (DF), dengue hemorrhagic fever, and dengue shock syndrome, both widely prevalent in tropical and subtropical regions. In 2019, a severe outbreak of DF occurred in Xishuangbanna, Yunnan province. Objective: To investigate the etiology and genotype of the causative agents of this severe dengue outbreak in Xishuangbanna. Methods: Between October and November 2019, the sera of patients clinically diagnosed with DF were collected in the first People's Hospital of Xishuangbanna. RNA was extracted from the sera and amplified by RT-PCR with flavivirus primers. Flavivirus-positive sera were then used to inoculate Aedes albopictus cells (C6/36); viral RNA was extracted from these cells, amplified, and sequenced with DENV E gene-specific primers. Sequence splicing and nucleotide homology genetic evolution analysis were carried out by biological software (DNAStar). Unique mutations in the E genes of isolated DENV were analyzed by SWISS-MODEL and PyMOL. Results: Of the 60 samples collected from DF patients, 39 tested positively with flavivirus primers. The DENV was isolated from 25 of the 39 positive seras, of which 20 showed cytopathic effects (CPE) and 5 were no CPE. In these 25 isolated nucleic acids, 21 strains of DENV-1, 3 strains of DENV-2, and 1 strain of DENV-3 were identified according to the sequence of E protein. In the four unique mutations (D52, Y149, L312, T386), D52 and Y149 in the E protein of DENV-1 were predicted to be exposed on the surface of the prefusion conformation. Conclusion: The 2019 outbreak of DF in Xishuangbanna area of Yunnan Province consists of at least three serotypes of DENV-1, DENV-2, and DENV-3, and the sources of these virus strains are of mixed and complicated origin.

Phosphatidylinositol (3,5)-bisphosphate machinery regulates neurite thickness through neuron-specific endosomal protein NSG1/NEEP21.

Phosphatidylinositol (3,5)-bisphosphate [PtdIns(3,5)P2] is a critical signaling phospholipid involved in endolysosome homeostasis. It is synthesized by a protein complex composed of PIKfyve, Vac14, and Fig4. Defects in PtdIns(3,5)P2 synthesis underlie a number of human neurological disorders, including Charcot-Marie-Tooth disease, child onset progressive dystonia, and others. However, neuron-specific functions of PtdIns(3,5)P2 remain less understood. Here, we show that PtdIns(3,5)P2 pathway is required to maintain neurite thickness. Suppression of PIKfyve activities using either pharmacological inhibitors or RNA silencing resulted in decreased neurite thickness. We further find that the regulation of neurite thickness by PtdIns(3,5)P2 is mediated by NSG1/NEEP21, a neuron-specific endosomal protein. Knockdown of NSG1 expression also led to thinner neurites. mCherry-tagged NSG1 colocalized and interacted with proteins in the PtdIns(3,5)P2 machinery. Perturbation of PtdIns(3,5)P2 dynamics by overexpressing Fig4 or a PtdIns(3,5)P2-binding domain resulted in mislocalization of NSG1 to nonendosomal locations, and suppressing PtdIns(3,5)P2 synthesis resulted in an accumulation of NSG1 in EEA1-positive early endosomes. Importantly, overexpression of NSG1 rescued neurite thinning in PtdIns(3,5)P2-deficient CAD neurons and primary cortical neurons. Our study uncovered the role of PtdIns(3,5)P2 in the morphogenesis of neurons, which revealed a novel aspect of the pathogenesis of PtdIns(3,5)P2-related neuropathies. We also identified NSG1 as an important downstream protein of PtdIns(3,5)P2, which may provide a novel therapeutic target in neurological diseases.

Impact of pulmonary arterial systolic pressure on patients with mitral valve disease combined with atrial fibrillation.

Objective: To determine whether different changes of pulmonary artery systolic pressure (PASP) after surgeries have an impact on the long-term outcomes in patients with rheumatic and degenerative mitral valve (MV) disease and atrial fibrillation. Methods: Between 2004 and 2016, 1,188 patients with rheumatic and degenerative MV disease undergoing MV and Cox-Maze procedure were identified. Clinic outcomes, as well as rhythm state and echocardiography indices in long-term follow-up were recorded. Patients were grouped by the changes of PASP (persistently normal, persistently increased, increased, and decreased) from preoperative estimation to follow-up. Results: A complete echocardiography was performed at baseline and after 5 years. During follow-up, free of death and atrial fibrillation (AF) off antiarrhythmic drugs was 90 and 61%, 78 and 41% at 5 and 10 years, respectively. Survival rate was higher in patients with persistently normal and became worse in patients with persistently increased and increased PASP (log-rank 166.0, P < 0.0001). Moreover, the patients with persistently normal PASP had a lowest risk of recurrent AF (SHR: 0817; CI: 0.765-0.872; P < 0.0001) after considering death as a competing risk. A persistently normal PASP at follow-up and degenerative MV disease were associated with improved survival and sinus rhythm (SR) maintenance at multivariable Cox regression analysis (P < 0.05). Conclusion: Patients with degenerative MV disease or have persistently normal PASP during follow-up have better survival and SR maintenance rate than patients with either rheumatic MV disease or persistently abnormal PASP.

Case Report: A Novel PAX3 Mutation Associated With Waardenburg Syndrome Type 1.

Background: Waardenburg Syndrome Type 1 (WS1) is a rare hereditary disease, which is usually caused by the mutations of PAX3 (paired box 3). Here, we reported a pedigree with WS1, which was caused by a novel mutation in PAX3. Case Report: In this present report, a 10-year-old boy and his twin sister from a Han Chinese family presented with iris pigmentary abnormality, synophrys, and broad and high nasal root. Their father presented premature whitening of the hair, but no iris pigmentary abnormality. Their aunts presented the same clinical characteristics with the twins and premature graying of hair. However, none of the patients reported hearing loss. The clinical diagnosis of the four patients from this pedigree was WS1. The whole exome sequencing (WES) revealed a novel mutation (c.959-5T>G) in the PAX3 gene, which could be responsible for the observed pathogenic of WS1 in this pedigree. The genetic test confirmed the diagnosis of WS1 in the four patients from the studied pedigree. Conclusion: This present study demonstrated that genetic test based on WES, an effective alternative to regular clinical examinations, helps diagnose WS1. The newly identified PAX3 gene mutation can expand the understanding of WS1.

Association of early elevated cardiac troponin I concentration and longitudinal change after off-pump coronary artery bypass grafting and adverse events: a prospective cohort study.

BACKGROUND: The elevation of troponin after coronary artery bypass grafting (CABG) is common This study aimed to investigate the association between very early cardiac troponin I (cTnI) concentration and its longitudinal change within 24 hours after CABG and 30-day adverse events. METHODS: This study prospectively enrolled 633 patients who underwent isolated off-pump CABG from January 2019 to May 2019. Serum cTnI levels were measured in all patients at two examinations within 24 hours postoperatively (1 hour and 12-18 hours), and a proportional hazards model was used to determine the association between cTnI levels and their change with adverse events, which were defined as a composite of 30-day mortality, stroke, heart failure, myocardial infarction (MI), and ventricular fibrillation. RESULTS: cTnI levels of the two examinations and absolute change of cTnI levels were significantly higher in the event group than in the non-event group (P<0.01, both). Earlier and later cTnI concentrations were associated with 30-day complications [adjusted hazard ration (HR) 1.598, 95% confidence interval (CI), 1.158-2.204 and HR 1.499, 95% CI, 1.228-1.831, respectively]. With regard to longitudinal change in cTnI levels, participants with persistently high levels of cTnI and those with progression from a low level to high level concentration experienced a significantly increased risk of adverse events than did participants who had a trend of persistently low cTnI levels (HR 3.105, 95% CI, 1.748-5.517 versus HR 2.944, 95% CI, 1.488-5.824). CONCLUSIONS: Longitudinal change in cTnI levels within 24 hours and early cTnI concentrations, even less than 1 hour after CABG, are associated with adverse events. These data will be useful in identifying patients at an increased risk of complications.

Comparison between Ozurdex and intravitreal anti-vascular endothelial growth factor treatment for retinal vein occlusion-related macular edema: A systematic review and meta-analysis of randomized controlled trials.

This systematic review aimed to evaluate the effectiveness and safety of intravitreal dexamethasone (DEX) implant and intravitreal anti-vascular endothelial growth factor (VEGF) treatments for macular edema (ME) secondary to retinal vein occlusion (RVO), central retinal vein occlusion (CRVO), and branch retinal vein occlusion (BRVO). The electronic databases comprehensively searched for the studies that compared DEX with anti-VEGF treatments in patients suffering from RVO-related ME. The effectiveness was estimated using best-corrected visual acuity (BCVA), central retinal thickness (CRT), and intraocular pressure (IOP). All data were analyzed by Review Manager (RevMan) 5.3. According to the meta-analysis from five randomized control trials, both DEX implant and anti-VEGF agent treatments were effective, but no significant differences in BCVA and CRT were observed between these two treatments. Novartis' two studies indicated that anti-VEGF agents significantly reduced the CRT compared with DEX implant at 6 months [weighted mean difference: 158.53 µm, 95% confidence interval (CI): (71.09, 245.96), P= 0.0004]. Furthermore, anti-VEGF agents showed some advantages on cataract formation [risk ratio (RR): 3.43, 95% CI: (1.35, 8.71), P= 0.009] and other adverse events [RR: 1.19, 95% CI: (1.09, 1.31), P= 0.0002] without heterogeneity (P = 0.20, I2 = 35%). Anti-VEGF agents were also effective treatments for cataract formation or less adverse events for RVO-related ME. In contrast, DEX implant had higher risk for IOP elevation and lower cataract incidence than anti-VEGF agents. Hence, complementary and alternative treatments are expected.

Comparison of intravitreal bevacizumab and ranibizumab used for myopic choroidal neovascularization: A PRISMA-compliant systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: To evaluate the effect of intravitreal bevacizumab (IVB) and ranibizumab (IVR) for the treatment of choroidal neovascularization (CNV) secondary to pathologic myopia (PM) by meta-analysis. METHODS: Pertinent publications of randomized controlled trials (RCTs) were identified through systemic searches of PubMed, EMBASE, Web of science, Cochrane Library, clinicaltrials.gov, CNKI, CQVIP, and Wanfang database. All comparative studies of IVB or IVR as treatment for CNV secondary to pathologic myopia were included. Meta-analysis of these RCTs was performed using Review Manager 5.3 software. The χ test and I values were used to analyze heterogeneity. Measurements included best-corrected visual acuity (BCVA) and central foveal thickness (CFT). RESULTS: A total of 3 randomized controlled clinical trials involving 158 eyes were included, 81 eyes in IVB group and 77 eyes in IVR group. Compared with baseline, at 1, 3, 6, and 12 months after IVB or IVR treatment, BCVA was significantly increased. Change of BCVA at 1, 3, 6, and 12 months did not vary significantly between IVB and IVR group (1 month: Z = 0.30, 95% CI = -0.08 to 0.11, P = .76; 3 months: Z = 0.36, 95% CI = -0.10 to 0.15, P = .72; 6 months: Z = 0.17, 95% CI = -0.10 to 0.12, P = .86; 12 months: Z = 0.64, 95% CI = -0.15 to 0.08, P = .52). CONCLUSION: Both IVR and IVB can significantly improve BCVA of eyes with mCNV, but there was no significant difference between the 2 therapies on the treatment of mCNV.

DENN domain-containing protein FAM45A regulates the homeostasis of late/multivesicular endosomes.

DENN (differentially expressed in normal cells and neoplasia) domain-containing proteins are a family of guanine nucleotide exchange factors (GEFs) for Rab small GTPases and coordinate a plethora of intracellular membrane trafficking events. FAM45A is a non-classical DENN domain protein, whose function was unknown. In this study, we characterized cellular roles of FAM45A. We found that FAM45A localized mainly in late/multivesicular endosomes. Depletion of FAM45A resulted in clustering of endosomes to the perinuclear region. The endocytosis of EGF receptor was impaired in FAM45A knockdown cells due to a delay in the early-to-late endosome transition. Furthermore, the secretion of selected exosome subpopulations was also attenuated in FAM45A knockdown cells. Consistent with these results, Rab27a and Rab27b, two Rabs involved in endosome motility and exosome biogenesis, were found to act downstream of FAM45A pathway. FAM45A colocalized with Rab27a/b and formed complex with them in a nucleotide-dependent manner. Taken together, FAM45A defines a novel regulatory step in the homeostasis of late endocytic pathway, including endosomal positioning, maturation and secretion, possibly through activating Rab proteins such as Rab27a/b.

Intraoperative method based on tricuspid annular circumference in patients with mild or no tricuspid regurgitation during left-sided cardiac valve surgery for the prophylactic tricuspid annuloplasty.

BACKGROUND: During left-sided cardiac valve surgery in patients with mild or no tricuspid regurgitation (TR), the tricuspid valve exploration plays a vital role in the decision-making of concomitant tricuspid annuloplasty. Currently lack of an appropriate standard to define tricuspid annular dilatation is a challenge. The aim of this study is to introduce and evaluate an alternative intraoperative method for Tricuspid Valve annuloplasty based on annular circumference that could trace the extent of annular dilatation and predict TR-progression, which can also guide the surgeons to intraoperative decision. METHODS: From January 2011 to December 2011, 131 patients (73 females, 58 males, and mean age 54±10.8) were selected for the study underwent left-sided cardiac valve surgery at Anzhen Hospital, all the subjects preoperatively diagnosed with non-significant TR. The enrolled subjects were followed-up over 5years for TR-progression. Tricuspid annular circumference (TAC) measurement was performed via special sizer for each patient, and the obtained values divided on the subject's body surface area (BSA) to achieve the tricuspid annular circumference index (TACI). The endpoint was set as the TR-progression by more than two grades, or a final TR grade ≥3+. RESULTS: The mean follow up period was 68±3.8 months (range, 60-77 months). In univariate, multivariate and logistic regression analysis three variables were noticed to be associated with TR progression, female gender (P<0.002), body mass index (BMI) (P<0.021), and intraoperatively measured TACI (P<0.001). But in multiple regression the TACI (OR 0.812; 95% CI: 0.748-0.883; P<0.001) was the single parameter which significantly related to TR-progression. Based on the receiver-operator curve (ROC), it was likely to derive an optimal cut-off 80.2 mm/m2 which could predict the postoperative development of TR with acceptable sensitivity and specificity 69%, 89%. CONCLUSIONS: Patients with mild or no TR undergoing left-sided valve surgery, intraoperative measurement of the TAC proved to be an ideal method to judge the tricuspid-annulus, it is capable to predict TR-progression. For prophylactic tricuspid repair a presumed TACI of 80.2 mm/m2 is recommended as an indicative threshold.

A predictor for mitral valve repair in patient with rheumatic heart disease: the bending angle of anterior mitral leaflet.

BACKGROUND: Mobility and flexibility of anterior mitral leaflet (AML) are considered to be the important factor for mitral valve (MV) repair in rheumatic population, we try to use the bending angle of AML to quantify its' mobility and flexibility and investigate whether it can predict the success of rheumatic MV repair or not. METHODS: Total 54 patients underwent rheumatic MV surgeries with mild lesions of subvalvular apparatus from August, 2017 to November, 2017 at the author institution, we divided the patients into MV repair and MV replacement groups which included directly MV replacement and repair attempt but failed repairing transfer to replacement intraoperatively. Patients' MV structure was carefully evaluated on transthoracic echocardiography (TTE) and scored by the Wilkins score (WS) preoperatively. The bending angle of AML was measured during systole and diastole at different level before surgery. RESULTS: The differences of patients' demographic characteristics between repair group and replacement group were not statistically significant (P value >0.05) and the differences among B-angle, T-angle, Bs-angle, C-angle of AML between repair group and replacement groups were not statistically significant (P value >0.05). Only BT-angle in repair group was significantly larger than that of replacement group (21.56°±3.84°, 10.29°±6.02°, respectively, P<0.001), therefore the BT-angle was tested as a predictor of reparability by observing the receiver operating characteristic (ROC) curve (ROC area: 0.944, standard error: 0.06, 95% CI: 0.826-1), BT-angle of AML on preoperative transthoracic echo of 15.5° or more predicts feasibility of rheumatic MV repair with 100% sensitivity and 85.7% specificity in patients with mild lesions of subvalvular apparatus. Logistic regression for a single area of calcification (diameter <0.8 cm) at commissure were shown that: ß: 0.08, Exp (ß): 1.083, P: 0.777>0.05, the minor single calcified area at commissure had no effect on reparability of rheumatic MV disease. The differences of total WS and each component score between repair group and replacement group were not statistically significant (P value >0.05). By observing the ROC curve for total WS (ROC area: 0.508), the WS cannot be a predictor for the rheumatic MV repair. CONCLUSIONS: The bending angle of AML which was considered as quantification of mobility and flexibility of AML can be a predictor for MV repair in patients with rheumatic heart disease (RHD). The small single area of commissural calcification had no effect on reparability of rheumatic MV disease. WS cannot appropriately predict the outcome of rheumatic MV repair.

A meta-analysis of late outcomes of mitral valve repair in patients with rheumatic heart disease.

BACKGROUND: Rheumatic heart disease (RHD) is a predominant health concern in developing countries. The aim of this meta-analysis was to evaluate the outcomes of mitral valve (MV) repair in patients with RHD, and identify predictors that may postoperatively affect treatment outcome. METHODS: A meta-analysis of eligible studies assessing patients undergoing MV repair with RHD and reporting the outcomes of MV repair, including 30-day mortality and long-term follow-up survival, MV reoperation rate and postoperative adverse events. Relevant English articles were searched up to 1 March, 2017 in Web of Science, PubMed, Google Scholar, Cochrane Library, EmBase, Elsevier, and Science Direct. Selected studies should meet all inclusion criteria, and underwent data extraction. RESULTS: A total of ten studies with 2,770 patients met all inclusion criteria, and were selected for assessment. Pooled analysis showed that 30-day mortality in patients with rheumatic MV disease after MV repair surgery was 1.9%, 95% confidence interval (CI) (0.8-2.9%); long-term survival was 97.3%, 95% CI (95.9-98.6%), and a freedom from reoperation rate of 93.6%, 95% CI (91.4-95.9%) was obtained; freedom from adverse events was 97.5%, 95% CI (95.2-99.8%). CONCLUSIONS: The outcome of rheumatic MV repair is outstanding in terms of low early mortality, high long-term survival and freedom from valve-related complications, which may be very common in patients after rheumatic MV replacement; meanwhile, MV reoperation rate after initial surgery is acceptable. Surgeons may try to repair MV in RHD when it is feasible.

Neuroprotective effects of gypenosides in experimental autoimmune optic neuritis.

AIM: To determine whether gypenosides have protective effects in experimental autoimmune optic neuritis (EAON). METHODS: Mice were randomly divided into seven groups: control group, model group, three different density gypenosides monotherapy, methylprednisolone monotherapy, combination of gypenosides and methylprednisolone group. The control group was subcutaneously injected with oil emulsion adjuvant and all other groups were subcutaneously immunized with an emulsified mixture of myelin oligodendrocyte glycoprotein (MOG) 35-55 peptide to induce EAON. Mice in the gypenosides groups were administered injections daily with three concentrations (15 mg/kg, 30 mg/kg, 45 mg/kg) of gypenosides respectively. Mice in the methylprednisolone group and the combination treatment group were injected daily with methylprednisolone (20 mg/kg) or methylprednisolone (20 mg/kg) + gypenosides (30 mg/kg), respectively. After MOG immunization, visual evoked potential (VEP), optical coherence tomography (OCT), and histopathologic examination were performed at 14, 20, 30, and 40d post-inoculation (p.i.). All results were expressed as mean±SEM. The data were evaluated by one-way ANOVA followed by Tukey or Games-Howell test. RESULTS: Compared with the control group, p2 latency was prolonged in the model group (P=0.041). Combination treatment can alleviated the change in VEP at 20d p.i. (P=0.012). Average peripapillary retinal nerve fiber layer (RNFL) thickness was reduced in the model group (P=0.000, 30d; P=0.000, 40d) and gypenosides treatment remarkably diminished the degree of RNFL degeneration at 30d and 40d p.i (P=0.000, 30d; P=0.000, 40d). The pathomorphological results showed a decrease in demye-lination (P=0.020) and inflammatory reactions in the combination group compared with the model group (20d p.i.). Gypenosides treatment also alleviated the degree of axonal loss (40d p.i.) (P=0.003). CONCLUSION: Treatment with gypenosides exerts protective effects on retinal nerve fibers and axons in EAON. When combined with gypenosides, methylprednisolone reduces demyelination in the acute stage of EAON.

Analysis of risk factors for recurrence after video-assisted pulmonary vein isolation of lone atrial fibrillation--results of 5 years of follow-up.

OBJECTIVE: The purpose of the present study was to assess the efficacy of the long-term results after video-assisted pulmonary vein isolation and left atrial appendage excision for lone atrial fibrillation (AF) and to determine the most significant risk factors for the long-term results. METHODS: From December 2006 to December 2012, 332 consecutive patients with lone AF underwent minimally invasive surgical ablation at our center. Of the 332 patients, 91, who had undergone video-assisted pulmonary vein isolation>5 years earlier, were evaluated in the present study (48 with paroxysmal AF, 21 with persistent AF, and 22 with long-standing persistent AF). The median follow-up period was 66 months. The primary endpoint was the success rate of video-assisted pulmonary vein isolation, defined as the absence of any atrial arrhythmia recurrence lasting >30 seconds at the clinical visit and on the electrocardiogram or long-term cardiac rhythm recording after discharge. RESULTS: During the follow-up period, 1 patient (1.1%) experienced a stroke and 4 (4.4%) died of noncardiac disease. At the 5-year follow-up point, 43 of 78 patients (55.1%) were in normal sinus rhythm. Of the 39 patients with paroxysmal AF and 39 with nonparoxysmal AF, 27 (69.2%) and 16 (44.1%) were in normal sinus rhythm, respectively. The results of the univariate and multivariate analyses of the preoperative risk factors for AF recurrence showed a left atrial diameter of ≥44 mm (hazard ratio, 5.56; 95% confidence interval, 1.68-18.387; P=.005) and an AF duration of ≥31.5 months (hazard ratio, 3.67; 95% confidence interval, 1.50-8.95; P=.004) were the most significant independent risk factors. CONCLUSIONS: Patients with lone AF with a large preoperative left atrial diameter and long AF duration will not be suitable for video-assisted pulmonary vein isolation alone and might need to undergo ablation of the lesions.