Assessing Health Risks from Bioaccessible PM2.5-bound Toxic Metals in Nanchang Metro: Implications for Metro Workers and Emissions Control.

High concentrations of PM2.5 with enriched levels of metallic constituents could significantly affect the health and comfort of metro employees. To avoid overestimating the exposure risks, we investigated the bioaccessibility of toxic metals (TMs) bound in PM2.5 from the Nanchang metro using Gamble's solution method, and qualitatively analyzed the impact of valence state and various sources on the bioaccessibility of TMs bound to PM2.5. The results showed that the bioaccessibility of the studied TMs ranged from 2.1% to 88.1%, with As, Ba, Co and Pb being the most bioaccessible and V, Fe and Cr being the less bioaccessible. The bioaccessibility of TMs in our subway PM2.5 samples varied based on their valence and species, showing higher valence states associated with increased bioaccessibility. Vehicle traffic, secondary aerosols and wheel/rail sources were found to be significantly and positively associated with the bioaccessibility of several TMs, implying a severe potential risk from these three sources. Although both non-carcinogenic and carcinogenic risks associated with total TMs were found to be high, only As and Cr(VI) posed a considerable carcinogenic risk to metro workers based on the bioaccessible fractions and were therefore priority pollutants. In addition, potential carcinogenic risk was found to be more severe in platform than that in ticket counter. The results indicate that considerable efforts are required to control and manage PM2.5 and the associated TMs in the Nanchang subway, particularly from traffic, wheel/rail and secondary sources, to protect the health of metro staff and the public.

Calcineurin B-like protein ZmCBL8-1 promotes salt stress resistance in Arabidopsis.

MAIN CONCLUSION: ZmCBL8-1 enhances salt stress tolerance in maize by improving the antioxidant system to neutralize ROS homeostasis and inducing Na+/H+ antiporter gene expressions of leaves. Calcineurin B-like proteins (CBLs) as plant-specific calcium sensors have been explored for their roles in the regulation of abiotic stress tolerance. Further, the functional variations in ZmCBL8, encoding a component of the salt overly sensitive pathway, conferred the salt stress tolerance in maize. ZmCBL8-1 is a transcript of ZmCBL8 found in maize, but its function in the salt stress response is still unclear. The present study aimed to characterize the protein ZmCBL8-1 that was determined to be composed of 194 amino acids (aa) with three conserved EF hands responsible for binding Ca2+. However, a 20-aa fragment was found to be missing from its C-terminus relative to another transcript of ZmCBL8. Results indicated that it harbored a dual-lipid modification motif MGCXXS at its N-terminus and was located on the cell membrane. The accumulation of ZmCBL8-1 transcripts was high in the roots but relatively lower in the leaves of maize under normal condition. In contrast, its expression was significantly decreased in the roots, while increased in the leaves under NaCl treatment. The overexpression of ZmCBL8-1 resulted in higher salt stress resistance of transgenic Arabidopsis in a Ca2+-dependent manner relative to that of the wild type (WT). In ZmCBL8-1-overexpressing plants exposed to NaCl, the contents of malondialdehyde and hydrogen peroxide were decreased in comparison with those in the WT, and the expression of key genes involved in the antioxidant defense system and Na+/H+ antiporter were upregulated. These results suggested that ZmCBL8-1 played a positive role in the response of leaves to salt stress by inducing the expression of Na+/H+ antiporter genes and enhancing the antioxidant system to neutralize the accumulation of reactive oxygen species. These observations further indicate that ZmCBL8-1 confers salt stress tolerance, suggesting that transcriptional regulation of the ZmCBL8 gene is important for salt tolerance.

Correlating somatic copy number alteration in aqueous humour cfDNA with chemotherapy history, eye salvage and pathological features in retinoblastoma.

BackgroundThis study determined to probe the potential association between somatic copy number alteration (SCNA) in retinoblastoma (RB) aqueous humour (AH) and pathological high-risk factors, clinical features and previous chemotherapy history. METHODS: Single-centre retrospective cohort study from including 58 AH samples collected from 58 patients diagnosed. Among them, 41 samples were collected after enucleation and 17 samples were collected before intravitreal chemotherapy. SCNAs were accessed by conducting shallow whole-genome sequencing in cell-free (cf) DNA of AH. HRs and ORs were applied to measure risk factors. RESULTS: Canonical RB SCNAs including 1q gain (87%), 2p gain (50%), 6p gain (76%), 16q loss (69%) were frequently detected. Non-classical RB SCNAs in AH including 17q gain (53%), 19q loss (43%), 7q gain (35%) were also commonly observed. 19q loss was significantly more common in patients with cT3c or worse stage than others (p=0.034). 2p gain(p=0.001) and 7q gain(p=0.001) were both more common in patients with primary enucleation than those with previous chemotherapy. Interestingly, both 2p gain (HR=1.933, p=0.027) and 7q gain (HR=2.394, p=0.005) might predict enucleation. Correlation analysis with pathological features among enucleated eyes showed that 19q loss can predict a higher risk for both massive choroid invasion (OR=4.909, p=0.038) and postlaminar optic nerve invasion (OR=4.250, p=0.043). DISCUSSION: Sequencing of AH cfDNA in RB can provide sufficient in vivo information. 19q loss was a potential signature of advanced cases clinically and pathologically.Repeated sampling from eyes receiving sequential chemotherapy should be conducted to evaluate fluctuation of SCNA in future study.

Carbohydrate antigen 125 in atrial fibrillation.

Atrial fibrillation is the most common arrhythmia in clinical settings. It is associated with an increased risk of death, stroke, and peripheral vascular embolism. Catheter ablation (CA) is an effective treatment for patients with AF. However, many studies have reported suboptimal outcomes, as AF recurrence rates often remain high after CA. Therefore, there is a need for early identification of patients who are prone to recurrence and require anti-inflammatory and/or antiarrhythmic treatment after CA. In recent years, Prediction of AF and AF recurrence after CA has become a hot topic in clinical practice. A lot of biomarkers (Such as B-type natriuretic peptide, N-terminal pro-BNP, high sensitivity C reactive protein etc.) have been identified as markers for predicting the risk of AF and AF recurrence after CA. Although these markers have been shown to predict AF and AF recurrence after CA, there are currently no relevant guidelines to indicate which of these markers have absolute predictive value. Therefore, Finding the appropriate indicators that can efficiently and accurately predict AF recurrence after AF ablation is important to provide the best treatment for each patient. These indicators still need exploration. Carbohydrate antigen 125 (CA-125) is a tumor marker suitable for the screening, diagnosis, and monitoring of ovarian malignant tumors. It has been widely studied in patients with heart failure. In recent years, the role of CA-125 in AF has been widely studied, and we provide a review in this article. It is wide availability and low cost provide additional advantages for its rapid implementation. This article reviews the role of CA-125 in patients with atrial fibrillation.

Intravenous versus super-selected intra-arterial chemotherapy in children with advanced unilateral retinoblastoma: an open-label, multicentre, randomised trial.

BACKGROUND: Super-selected intra-arterial chemotherapy has increasingly been used as conservative management for retinoblastoma during the past decade. However, the absence of evidence from randomised controlled trials engendered controversy in the administration route of chemotherapy. We aimed to assess the efficacy and safety of intra-arterial chemotherapy compared with intravenous chemotherapy. METHODS: This open-label, multicentre, randomised trial was done at six hospitals in China. Patients with new-onset unilateral group D or E retinoblastoma (poorly defined, large, or very large tumours, according to the International Intraocular Retinoblastoma Classification) without high-risk clinical factors were included. Patients were randomly assigned (1:1) to receive intra-arterial chemotherapy (injections of 0·5 mg/kg [or depending on age] melphalan with 20 mg carboplatin [first and third cycles] or with 1 mg topotecan [second and fourth cycles]) or intravenous chemotherapy (0·05 mg/kg [or 1·5 mg/m2] vincristine, 5 mg/kg [or 150 mg/m2] etoposide, and 18·6 mg/kg [or 560 mg/m2] carboplatin for six cycles). After intra-arterial chemotherapy, patients received a subcutaneous injection of 0·1 mL nadroparin calcium twice at a 12 h interval. Both intra-arterial and intravenous chemotherapy cycles were completed every 4 weeks. No masking was done, except of independent statisticians, who were masked to the allocation information. The primary outcome was 2-year progression-free globe salvage rate, defined as the time from randomisation to tumour progression or enucleation, whichever occurred first, and was analysed by intention to treat. We also recorded predefined safety outcomes (myelosuppression and ophthalmic arterial stenosis or occlusion) and severe adverse events likely to be related to study treatment. The study is registered with the Chinese Clinical Trial Registry, ChiCTR-IPR-15006469, and is complete. FINDINGS: Between June 1, 2015, and June 1, 2018, 234 patients with newly diagnosed retinoblastoma were screened and 143 eligible patients (median age 23·6 months [IQR 14·0-31·9]) were enrolled and randomly assigned to the intra-arterial chemotherapy group (n=72) or the intravenous chemotherapy group (n=71). At a median follow-up of 35·8 months (IQR 28·4-43·0), the 2-year progression-free globe salvage rate was 53% (38 of 72 patients) in the intra-arterial chemotherapy group and 27% (19 of 71 patients) in the intravenous chemotherapy group (risk ratio 1·97, 95% CI 1·27-3·07, p=0·0020). Myelosuppression was less common in the intra-arterial chemotherapy group than in the intravenous chemotherapy group (37 [51%] of 72 patients vs 50 [70%] of 71 patients; 0·73, 95% CI 0·56-0·96, p=0·021) and less severe (ptrend=0·0070). In the intra-arterial chemotherapy group, two (3%) of 72 patients had ophthalmic artery occlusion and 13 (18%) patients had ophthalmic artery stenosis. INTERPRETATION: Our findings show that intra-arterial chemotherapy could significantly improve the globe salvage rate in children with advanced unilateral retinoblastoma compared with intravenous chemotherapy, with mild systemic complications and no difference in overall survival rate. Intra-arterial chemotherapy could be an acceptable first-line treatment in children with advanced unilateral retinoblastoma. FUNDING: Scientific Research Program of the National Health and Family Planning Commission of China, the Clinical Research Plan of Shanghai Hospital Development Center, the National Natural Science Foundation of China, and the Science and Technology Commission of Shanghai Municipality.

Research on the Directional Adaptability of a Self-Adaptive Energy Harvester.

With the continuous development of wireless sensor networks (WSNs), multi-directional energy harvesting technology has received widespread attention from scholars. In order to evaluate the performance of multi-directional energy harvesters, this paper uses a directional self-adaptive piezoelectric energy harvester (DSPEH) as an example, defines the direction of the excitation in three-dimensional space, and studies the influence of excitations on the key parameters of the DSPEH. The rolling angle and pitch angle are used to define complex excitations in three-dimensional space, and the dynamic response of the excitation changes in a single direction and multiple directions is discussed. It is noteworthy that this work presents the concept of "Energy Harvesting Workspace" to describe the working ability of a multi-directional energy harvesting system. The workspace is expressed by the excitation angle and voltage amplitude, and energy harvesting performance is evaluated by the volume-wrapping method and area-covering method. The DSPEH exhibits good directional adaptability in two-dimensional space (rolling direction); in particular, when the mass eccentricity coefficient is r = 0 mm, 100% of the workspace in two-dimensional space is obtained. The total workspace in three-dimensional space depends entirely on the energy output in the pitch direction.

An n-valued neutrosophic set method for the assessment of an offshore oil spill risk.

With the development of maritime transportation, oil spill accidents occur frequently. In this paper, a scientific and reasonable assessment of ship oil spills, offshore oil platform oil spills, and subsea pipeline oil spills is carried out, and a risk assessment method of an offshore oil spill based on an n-value neutrosophic set is proposed. First, the oil spill risk evaluation index systems of these three risk sources are constructed, respectively, and the entropy weight method is used to calculate the weight. Second, we establish a risk assessment model under the n-value neutrosophic environment. Furthermore, we use the n-value neutrosophic-weighted arithmetic average (NVNWAA) to calculate the risk levels of the following three risk sources: ship oil spills, offshore oil platform spills, and submarine pipeline spills. Finally, according to the results of the risk assessment, the countermeasures to strengthen the preventive measures of oil spill accidents are put forward.

Anemia and Bone Marrow Suppression After Intra-Arterial Chemotherapy in Children With Retinoblastoma: A Retrospective Analysis.

Background: Retinoblastoma (Rb) is a common ocular malignant tumor in children. Intra-arterial chemotherapy (IAC) has been widely used in children with Rb and has achieved an ideal therapeutic effect. However, IAC has side effects, including anemia and bone marrow suppression, for which explicit evidence on the risk factors is lacking. This study aimed to evaluate the covariates that may affect the occurrence of anemia and bone marrow suppression in children with Rb after IAC. Methods: Children with Rb admitted between May 2019 and January 2021 were included into the study. The differences in the number of children with anemia and bone marrow suppression before and after IAC according to different covariates were recorded. All potential impact factors were included into the univariate and multivariate regression models to identify the related covariates of post-IAC anemia and bone marrow suppression. Results: Data of 282 children with Rb were retrospectively collected. After IAC, children with Rb had increased severities of anemia (p <0.0001, chi-square test) and bone marrow suppression (p = 0.001, chi-square test). Moreover, the number of children with Rb who had an increased cross-level change in the severity of anemia and degree of bone marrow suppression was 80 (41.24%) and 64 (32.49%), respectively. The univariate regression analysis showed that numerous factors (such as pre-IAC intravenous chemotherapy, results of pre-IAC routine blood tests, and some serological indicators for liver and kidney function) affected the anemia severity and degree of bone marrow suppression in children with Rb after IAC. Additionally, the predictive model of the multivariate regression could predict anemia and bone marrow suppression. Conclusion: Children with Rb may have an increased risk of anemia and bone marrow suppression after IAC, but this is temporary and can be influenced by several factors. Therefore, IAC should be maintained as the standard of care. We generated predictive equations for predicting anemia severity and degree of bone marrow suppression, which can guide the prediction and timely control of anemia and bone marrow suppression after IAC.

Monitoring Retinoblastoma by Machine Learning of Aqueous Humor Metabolic Fingerprinting.

The most common intraocular pediatric malignancy, retinoblastoma (RB), accounts for ≈10% of cancer in children. Efficient monitoring can enhance living quality of patients and 5-year survival ratio of RB up to 95%. However, RB monitoring is still insufficient in regions with limited resources and the mortality may even reach over 70% in such areas. Here, an RB monitoring platform by machine learning of aqueous humor metabolic fingerprinting (AH-MF) is developed, using nanoparticle enhanced laser desorption/ionization mass spectrometry (LDI MS). The direct AH-MF of RB free of sample pre-treatment is recorded, with both high reproducibility (coefficient of variation < 10%) and sensitivity (low to 0.3 pmol) at sample volume down to 40 nL only. Further, early and advanced RB patients with area-under-the-curve over 0.9 and accuracy over 80% are differentiated, through machine learning of AH-MF. Finally, a metabolic biomarker panel of 7 metabolites through accurate MS and tandem MS (MS/MS) with pathway analysis to monitor RB is identified. This work can contribute to advanced metabolic analysis of eye diseases including but not limited to RB and screening of new potential metabolic targets toward therapeutic intervention.

Risk factors for ophthalmic artery stenosis and occlusion in patients with retinoblastoma treated with intra-arterial chemotherapy.

PURPOSE: To explore the risk factors for ophthalmic artery (OA) stenosis and occlusion after intra-arterial chemotherapy (IAC) with selective ophthalmic artery catheterisation (OAC) in the treatment of retinoblastoma. DESIGN: Retrospective, single centre case-control study. METHODS: The study was conducted including consecutive patients with unilateral or bilateral intraocular retinoblastoma undergoing IAC between June 2016 and June 2019 with a follow-up time of 4 years. Main outcomes are rate of IAC-induced OA occlusion and OA diameter. RESULTS: 346 attempted OAC infusions were successful. The total incidence of OA occlusion was 15.89%. The occlusion and control groups were similar in patients' age, sex and disease stage. Median OA diameter was 0.49 mm in those with OA occlusion, and 0.66 mm in those without occlusion. In the occlusion group, the OA diameter difference was significantly larger between the first IAC and the final IAC (0.22mm vs 0.12mm, p=0.001). In both groups, the median number of IAC treatments was 3. Multivariate Cox regression models included initial OA diameter (OR: 0.005, p=0.001), ratio of OA orifice diameter differences between first and last IAC to the initial OA orifice diameter (OR: 4.661, p=0.003), and number of IAC (OR: 1.538, p=0.042) as clinical features significantly associated with OA occlusion. CONCLUSIONS: The OA diameter at first IAC treatment, the ratio of OA orifice diameter differences between first and last IAC to the initial OA orifice diameter and total number of IAC treatments may be three main clinical predictors for OA occlusion after IAC for retinoblastoma.

Contemporary Update of Retinoblastoma in China: Three-Decade Changes in Epidemiology, Clinical Features, Treatments, and Outcomes.

PURPOSE: To report three-decade changes of clinical characteristics, progress of treatments, and risk factors associated with mortality and enucleation in patients with retinoblastoma in China. DESIGN: Retrospective cohort study. METHODS: This multicenter study included 2552 patients diagnosed with retinoblastoma in 38 medical centers in 31 provinces in China from 1989 to 2017, with follow-up data. Kendall's tau-b value was used to describe correlation coefficients between the three eras (between 1989 and 2008, between 2009 and 2013, and between 2014 and 2017) and clinical or demographic features. Hazard ratios and odds ratios were applied to measure risk factors. RESULTS: A total of 324 (13%) patients died and 1414 (42%) eyes were removed. The 1-year, 3-year, and 5-year overall survival rates were 95%, 86%, and 83%, respectively. Patients were diagnosed at a better stage by International Classification for Retinoblastoma over time (Kendall's tau-b value = -0.084, P < .001). Pathological risk factors were also observed less in recent eras. New conservative therapies were adopted and used in more patients. The eye removal rate gradually decreased (Kendall's tau-b value = -0.167, P < .001). The overall survival rates were 81%, 83%, and 91% in the three eras. By multivariate Cox regression, bilateral tumors and extraocular extension were identified as risk factors for death. Among intraocular disease, Group E indicated higher risk of mortality. By multivariate logistics regression, unilateral tumors, earlier era of diagnosis, and extraocular extension were risk factors for eye salvage failure. Among intraocular retinoblastoma, Groups D and E had higher risk of eye salvage failure. CONCLUSIONS: Patients were diagnosed at an earlier stage in recent eras. Conservative therapies, including intra-arterial chemotherapy, were increasingly being used. The above changes may contribute to the decreasing enucleation rate. Although no significant impact was identified on the mortality by the three eras, a decreasing trend was shown.

Eye-Preserving Therapies for Advanced Retinoblastoma: A Multicenter Cohort of 1678 Patients in China.

PURPOSE: This study attempted to estimate the impact of eye-preserving therapies for the long-term prognosis of patients with advanced retinoblastoma with regard to overall survival and ocular salvage. DESIGN: Retrospective cohort study covering all 31 provinces (38 retinoblastoma treating centers) of mainland China. PARTICIPANTS: One thousand six hundred seventy-eight patients diagnosed with group D or E retinoblastoma from January 2006 through May 2016. METHODS: Chart review was performed. The patients were divided into primary enucleation and eye-preserving groups, and they were followed up for survival status. The impact of initial treatment on survival was evaluated by Cox analyses. MAIN OUTCOME MEASURES: Overall survival and final eye preservation. RESULTS: After a median follow-up of 43.9 months, 196 patients (12%) died, and the 5-year overall survival was 86%. In total, the eyeball preservation rate was 48%. In this cohort, 1172 patients (70%) had unilateral retinoblastoma, whereas 506 patients (30%) had bilateral disease. For patients with unilateral disease, 570 eyes (49%) underwent primary enucleation, and 602 patients (51%) received eye-preserving therapies initially. During the follow-up (median, 45.6 months), 59 patients (10%) from the primary enucleation group and 56 patients (9.3%) from the eye-preserving group died. Multivariate Cox analyses indicated no significant difference in overall survival between the 2 groups (hazard ratio [HR], 1.25; 95% confidence interval [CI], 0.85-1.84; P = 0.250). For patients with bilateral disease, 95 eyes (19%) underwent primary enucleation, and 411 patients (81%) received eye-preserving therapies initially. During the follow-up (median, 40.1 months), 12 patients (13%) from the primary enucleation group and 69 patients (17%) from the eye-preserving group died. For bilateral retinoblastoma with the worse eye classified as group E, patients undergoing primary enucleation exhibited better overall survival (HR, 2.35; 95% CI, 1.10-5.01; P = 0.027); however, this survival advantage was not evident until passing 22.6 months after initial diagnosis. CONCLUSIONS: Eye-preserving therapies have been used widely for advanced retinoblastoma in China. Patients with bilateral disease whose worse eye was classified as group E and who initially underwent eye-preserving therapies exhibited a worse overall survival. The choice of primary treatment for advanced retinoblastoma should be weighed carefully.

[Silencing LncRNA SNHG7 alleviates hypoxia/reoxygenation-induced cardiomyocyte damage by regulating the expression of miR-181b-5p].

OBJECTIVE: To study the effect of silencing LncRNA SNHG7 on hypoxia/reoxygenation (H/R)-induced cardiomyocyte injury and its targeted regulation on miR-181b-5p. METHODS: Rat cardiomyocytes H9c2 were cultured in vitro and randomly divided into control group, H/R group, H/R + si-NC group, H/R + si-SNHG7 group, H/R + si-SNHG7 + anti-miR-NC group and H/R + si-SNHG7 + anti-miR-181b-5p group. The content of lactate dehydrogenase (LDH), malondialedhyde (MDA) and the activity of superoxide dismutase (SOD) were detected. Flow cytometry was carried out to detect the rate of apoptosis. qRT-PCR was used to detect the expression of SNHG7 and miR-181b-5p. Dual luciferase report experiment was used to verify the targeting relationship between SNHG7 and miR-181b-5p. Western blotting was used to detect the expression of Bax and Bcl-2. RESULTS: Compared with the control group, the H/R group showed significantly increased SNHG7 expression in cardiomyocytes, reduced miR-181b-5p expression, higher levels of LDH and MDA, reduced activity of SOD, increased cell apoptosis rate, higher level of Bax protein, and reduced level of Bcl-2 protein (all P< 0.05). Compared with the H/R and H/R + si-NC groups, the H/R + si-SNHG7 group had significantly reduced level of LDH and MDA, increased activity of SOD, reduced apoptosis rate, reduced level of Bax protein, increased level of Bcl-2 protein (all P< 0.05). The dual luciferase report experiment confirmed that SNHG7 could target miR-181b-5p. Interference with the expression of miR-181b-5p could reduce the effect of silencing SNHG7 on H/R-induced cardiomyocyte oxidative stress and apoptosis. CONCLUSION: Silencing SNHG7 may inhibit H/R-induced cardiomyocyte oxidative stress and apoptosis by up-regulating the expression of miR-181b-5p, thereby exerting a protective effect on cardiomyocytes.

Comparison of Intra-Arterial Chemotherapy Efficacy Delivered Through the Ophthalmic Artery or External Carotid Artery in a Cohort of Retinoblastoma Patients.

Purpose: To evaluate the efficacy of an external carotid artery (ECA) alternative route in intra-arterial chemotherapy (IAC) for treatment of retinoblastoma. Methods: In this retrospective, single-centre, case-control study, 98 retinoblastoma patients who received successful IAC were included. The drug delivery routes were the primary ophthalmic artery (OA) route and the ECA route when OA catheterization was not feasible. Results: A total of 337 successful IAC procedures were performed in our study, of which 32 (9.5%) procedures were performed through the ECA route. Eighteen eyes (18.4%) accepted at least one IAC through branches of the ECA. Statistical analysis showed that there was no significant difference in ocular clinical results (enucleation, death, recurrence and event-free) between the ECA and OA routes. No significant association was found between the route of drug delivery and the ocular survival time (p = 0.69). The use of ECA catheterization in at least one IAC cycle was not a predictor of enucleation (HR: 1.58; 95% CI: 0.56-4.46, p = 0.39). The increasing number of procedures through the ECA route did not increase the risk of enucleation (HR: 1.64; 95% CI: 0.42-6.39, p = 0.48). Conclusion: The ECA alternative route did not affect the efficacy of IAC in retinoblastoma. When the standard OA approach is not feasible, ECA system catheterization should be considered.

Clinical characteristics and germline mutation spectrum of RB1 in Chinese patients with retinoblastoma: A dual-center study of 145 patients.

Retinoblastoma (Rb) is the most common primary intraocular childhood malignancy and one of the main causes of blindness in children. In China, most tumors are diagnosed at an advanced stage and have relatively poor outcomes compared to developed countries. Here, we aimed to update the clinical manifestations and RB transcriptional corepressor 1 (RB1) mutation spectrum in Chinese Rb patients. Medical charts of 184 eyes in 145 Chinese Rb patients belonging to unrelated families were reviewed. Genomic DNA was isolated from peripheral blood of the patients and their parents. Mutation analysis of whole coding regions, promoter regions and flanking splice sites in the RB1 gene was performed. In addition, multiplex ligation-dependent probe amplification (MLPA) was done to detect gross aberrations. Germline RB1 mutations were observed in 37.2% (54/145) of Rb patients. RB1-mutated patients presented with earlier age of diagnosis (p = 0.019), with a significantly larger proportion of bilateral cases (p = <0.001) and secondary malignancies (p = 0.027) relative to those without RB1 mutations. For ocular clinical presentations, RB1-mutated retinoblastomas presented with a larger proportion of ectropion uveae (p = 0.017) and iris neovascularization (p = 0.001). These RB1 mutations comprised of 13 (24.1%) nonsense mutation, 13 (24.1%) splicing mutations, 11 (20.4%) frameshift deletions, 11 (20.4%) gross mutations, 3 (5.6%) missense mutations, 2 (3.7%) promoter mutations and 1 (1.9%) non-frameshift deletion. In addition, 8 novel RB1 mutations were identified. These germline RB1 mutations were not related to age at diagnosis or laterality. Here, we provide a comprehensive spectrum of RB1 germline mutations in Chinese Rb patients and describe correlations between RB1 mutations and clinical presentations. Our study also provides new evidence that will inform management and genetic counselling of Rb patients and families.

[The Effect and Mechanism of Hyperoside on High Glucose-induced Oxidative Stress Injury of Myocardial Cells].

OBJECTIVE: To explore the effect and mechanism of hyperoside on high glucose-induced oxidative stress injury of myocardial cells. METHODS: Oxidative stress injury of myocardial cells was simulated by treating with high glucose. Cells were divided into five groups: control group (5.5 mmol/L glucose); high glucose model group (35 mmol/L glucose); hyperoside protection groups (35 mmol/L glucose +4, 8, 20 nmol/L hyperoside). Cells were incubated for 48 h. The cell viability was detected by CCK-8. Apoptosis was measured through flow cytometry. The level of ROS was tested by Reactive Oxygen Species Assay Kit DCFH-DA with flow cytometer. The level of SOD and MDA was detected by SOD Assay Kit and MDA Assay Kit respectively. The protein levels of phosphatidylinositide 3-kinases (PI3K), protein kinase B (AKT), p-AKT, nuclear factor erythroid 2-related factor 2 (Nrf2) and p-Nrf2 were detected by Western blot. The activation of AKT was analyzed by immunofluorescence staining. RESULTS: Compared with control group, the cell viability, the levels of SOD, the expression of PI3K, the ratio of p-AKT/AKT and p-Nrf2/Nrf2 and the percentage of AKT positive cells in high glucose group were decreased with enhancive apoptosis and levels of ROS and MDA (P<0.05). Compared with high glucose group, the cell viability, the levels of SOD, the expression of PI3K, the ratio of p-AKT/AKT and p-Nrf2/Nrf2 and the percentage of AKT positive cells in hyperoside group (4, 8, 20 nmol/L) were increased with reduced apoptosis and levels of ROS and MDA (P<0.05). CONCLUSION: Hyperoside protects myocardial cells against oxidative stress injury via activation of PI3K/AKT/Nrf2 signal pathway.

Intra-arterial chemotherapy for unilateral advanced intraocular retinoblastoma: Results and short-term complications.

Intra-arterial chemotherapy (IAC) has become an essential technique for the management of advanced intraocular retinoblastoma (RB). In this study, the aim of this article is to describe the clinical results and the short-term complications of IAC performed in our hospital.We retrospectively analyzed patients with newly diagnosed unilateral advanced intraocular (group D or E) RB undergoing IAC from October 2016 to December 2017 in our hospital. We recorded the data including age, gender, cycles of IAC, pathway of arteries approached (ophthalmic artery or middle meningeal artery), ocular and systematic complications, globe salvage.Sixty-one patients underwent IAC performing 189 procedures with a median of 3.1 sessions per eye (range, 1-5 sessions). The overall globe salvage rate is 78.7% (Group D (84.2%), and Group E (69.6%) and followed-up. Short-term ocular complications include eyelid edema (15 cases), ptosis (5 cases), forehead congestion (3 cases), retina hemorrhage (5 cases), choroid atrophy (2 cases), phthisis bulbi (1 case), bradycardia and hypotension during the procedure (7cases), myelosuppressions (6 cases), and nausea and vomiting (5cases).IAC is safe and effective for the treatment of unilateral advanced intraocular RB with a very low complication rate.

The evolution of refractive status in Chinese infants during the first year of life and its affected factors.

AIM: To study the evolution of the refractive status and examine the affected factors in infants during the first year of life in a large sample size in China. METHODS: A total of 1258 babies (2516 eyes) aged 32wk gestational age to 1y participated in the study, including 766 premature and 492 full-term infants. First, each baby received an orthoptic examination, slit-lamp checking and fundus imaging. Patients with diseases which might affect refractive status were excluded from the cohort. The cycloplegia retinoscopy was performed. Their neonatal histories were reviewed. Each measurement contained the refractive status and calculation of the spherical equivalent (SE). RESULTS: Refractive state showed an average hyperopia of +0.94±1.63 D at early ages, followed by a trend toward more hyperopia. The refractive state reached the top (+2.43±1.46 D) at the age of one to two months. Then gliding till one year old when the refractive state reached +0.59±1.41 D. The prevalence of astigmatism was 42.17% in the study, being 2.82% myopic astigmatism and 39.35% hyperopic astigmatism. The 94.1% of hyperopic astigmatism was with-the-rule astigmatism and 71.83% of myopic astigmatism was with-the-rule astigmatism. Refractive state between boys and girls was different. The mean SE of boys was +1.97±1.57 D, while that of girls was +1.79±1.46 D, and the difference was significant. CONCLUSION: Before one year old, the change of refractive status is associated with checking age and sex. At the age of one to two months, the degree of hyperopia reaches the top. Boys have more hyperopic degree than girls, and with-the-rule astigmatism is predominant. Excluding premature infants with advanced retinopathy of prematurity, premature and full-term children have same refraction status.

Imipramine protects retinal ganglion cells from oxidative stress through the tyrosine kinase receptor B signaling pathway.

Retinal ganglion cell (RGC) degeneration is irreversible in glaucoma and tyrosine kinase receptor B (TrkB)-associated signaling pathways have been implicated in the process. In this study, we attempted to examine whether imipramine, a tricyclic antidepressant, may protect hydrogen peroxide (H2O2)-induced RGC degeneration through the activation of the TrkB pathway in RGC-5 cell lines. RGC-5 cell lines were pre-treated with imipramine 30 minutes before exposure to H2O2. Western blot assay showed that in H2O2 -damaged RGC-5 cells, imipramine activated TrkB pathways through extracellular signal-regulated protein kinase/TrkB phosphorylation. TUNEL staining assay also demonstrated that imipramine ameliorated H2O2 -induced apoptosis in RGC-5 cells. Finally, TrkB-IgG intervention was able to reverse the protective effect of imipramine on H2O2 -induced RGC-5 apoptosis. Imipramine therefore protects RGCs from oxidative stress-induced apoptosis through the TrkB signaling pathway.