Resilience and adaptation: a mixed-methods exploration of COVID-19's influence on neonatal residency education in China.

BACKGROUND: This study aimed to assess the impact of the pandemic of the coronavirus disease 2019 (COVID-19) on neonatology residency training in a tertiary children's hospital in Chongqing, located in southwest China. Specifically, the study encompassed the effects on residents' education, lived experiences, well-being, and the quality of neonatal care delivered. As higher educational institutions adapt to the post-COVID-19 era after the pandemic disruption, it is imperative that educational designers/academics learn from their experiences and challenges in curriculum design and delivery, ensuring quality and relevance in education. METHODS: This study employed a mixed-methods approach to investigate the influence of the COVID-19 pandemic on neonatology residency training at a tertiary children's hospital in Chongqing. The first phase surveyed residents' perceptions and experiences of their clinical education and well-being during the crisis. The second phase compared the quality of neonatal care between the pre-pandemic and pandemic periods. RESULTS: The survey of 123 neonatology residents examines the effects of COVID-19 on their learning, training, and mental health. The survey showed that most residents adapted well to the situation. Still, some faced challenges in their clinical education and experiences, such as reduced clinical exposure and opportunities to see rare diseases and conditions. A retrospective analysis of clinical data revealed that 7,151 neonates were admitted to the neonatology department during the study period. There was a 27.6% decrease in neonatal admissions during COVID-19, with more premature births and transfers. Residents conducted fewer clinical procedures but managed more complex cases. During COVID, hospital stays and costs were higher, but antibiotic use was lower. Although the case-mix index (CMI) score increased during the pandemic (1.25 vs. 1.18, p < 0.05), there was no significant difference in the rates of readmission within 7 days or poor prognosis. CONCLUSIONS: Despite reduced clinical exposure, the quality of neonatal care was maintained through innovative training methods that enhanced comprehensive residency programs. The study suggested that neonatology residency education remained effective and resilient during the crisis. Exceptional health professional education is vital to train qualified physicians and enhance healthcare systems for future challenges.

Embryonic stem cell extracellular vesicles reverse the senescence of retinal pigment epithelial cells by the p38MAPK pathway.

Retinal pigment epithelial (RPE) cellular senescence is regarded as an initiator for age-related macular degeneration (AMD). We previously demonstrated that by the coculture way, embryonic stem cells (ESCs) can reverse the senescence of RPE cells, but xenograft cells can cause a plethora of adverse effects. Extracellular vesicles (EVs) derived from ESCs can act as messengers to mediate nearby cell activities and have the same potential as ESCs to reverse RPE senescence. Furthermore, ESC-EVs have achieved preliminary efficacy while treating many age-related diseases. The present study aimed to test the effect of ESC-EVs on the replicative senescence model of RPE cells as well as its mechanism. The results showed that ESC-EVs enhanced the proliferative ability and cell cycle transition of senescent RPE cells, whereas reduced the senescence-associated galactosidase (SA-ß-gal) staining rate, as well as the levels of mitochondrial membrane potential (MMP) and reactive oxygen species (ROS). Moreover, classical markers of cellular senescence p21WAF1/CIP1 (p21) and p16INK4a (p16) were downregulated. The bioinformatic analysis and further study showed that the inhibition of the p38MAPK pathway by ESC-EVs played a pivotal role in RPE cellular senescence-reversing effect, which was ameliorated or even abolished when dehydrocorydaline were administrated simultaneously, demonstrating that ESC-EVs can effectively reverse RPE cellular senesence by inhibiting the p38MAPK pathway, thus highlights the potential of ESC-derived EVs as biomaterials for preventative and protective therapy in AMD.

Evaluation of antibiotic stewardship among near-term and term infants admitted to a neonatal unit.

To evaluate the safety and effectiveness of evidence-based antibiotic stewardship in a neonatal unit in China. The study period consisted of two phases, one retrospective (the baseline period, January to December 2018, and the transition period, January 2019 to August 2020) and one prospective intervention period (September 2020 to August 2021). During the prospective period, evidence-based antibiotic stewardship was applied to neonates with suspected infections, pneumonia, and culture-negative sepsis. The antibiotic stewardship included the observation form of neonatal infections, antibiotic therapy of no more than 48 h for suspected infections, and 5 days for pneumonia and culture-negative sepsis. The change in antibiotic use measured by days of therapy per 1000 patient-days between the baseline and intervention period was analyzed. Safety outcomes included reinitiation of antibiotics within 14 days, length of stay, occurrence of late-onset sepsis and necrotizing enterocolitis (Bell stage ≥ II), multidrug-resistant organism infections, and mortality. A total of 7705 neonates were enrolled during the baseline (n = 4804) and the intervention periods (n = 2901). The total antibiotic usage during the baseline period was 771 days of therapy per 1000 patient-days, while that was 525 days of therapy per 1000 patient-days during the intervention period, indicating a 32% decrease in antibiotic consumption. No significant difference in safety outcomes was observed between the baseline and intervention period (P > 0.05), whereas the length of stay was longer during the intervention period (P < 0.001). CONCLUSION: The evidence-based antibiotic stewardship can safely and effectively reduce antibiotic use and shorten the duration of therapy in the neonatal unit. WHAT IS KNOWN: • Overuse of antibiotics has been associated with adverse events in neonates, including necrotizing enterocolitis, multidrug-resistant organism infections, and death. • More clinical effectiveness evidence is needed to support antibiotic stewardship of neonates in China. WHAT IS NEW: • Using prospective audit, targeted stewardship interventions, this study shows that a 32% reduction in overall antibiotic consumption was achieved safely. • Implementation of evidence-based neonatal antibiotic stewardship, including the observation form of neonatal infections, antibiotic therapy of no more than 48 h for suspected infections, and 5 days for pneumonia and culture-negative sepsis, is safe and effective among newborns in a developing country.

Synthesis and biological assessment of indole derivatives containing penta-heterocycles scaffold as novel anticancer agents towards A549 and K562 cells.

Herein, a new series of 2-chloro-N-(5-(2-oxoindolin-3-yl)-4H-pyrazol-3-yl) acetamide derivatives containing 1,3,4-thiadiazole (10a-i) and 4H-1,2,4-triazol-4-amine (11a-r) moiety was designed, synthesised as novel anticancer agents. The antiproliferative activity values indicated that compound 10 b stood as the most potent derivative with IC50 values of 12.0 nM and 10 nM against A549 and K562 cells, respectively. Mechanism investigation and docking studies of 10 b indicated that it possessed good apoptosis characteristic and dose-dependent growth arrest of A549 and K562 cells, blocked cell cycle into G2/M phase. Interestingly, 10 b suppressed the growth of A549 and K562 cells via modulation of EGFR and p53-MDM2 mediated pathway.

Tear film cytokines as prognostic indicators for predicting early recurrent pterygium.

Cytokine profiles in tears have become a noninvasive biomarker for various ocular surface diseases. Therefore, the preoperative profile of cytokines in tear samples of 89 primary pterygium patients were obtained from Zhongshan Ophthalmic Center during 2015-2017. Compared to the tear cytokines in primary groups, the concentrations of IL-8, MMP-1, MMP-9, bFGF and VEGF were generally higher in recurrent pterygium group. The five cytokines were used to build diagnostic models by multiple machine learning algorithms, which can accurately distinguish non-recurrent and recurrent samples of primary pterygium patients. Besides, these cytokines were significantly associated with Recurrent-free survival (RFS) time in pterygium patients and further applied to develop a prognostic model which can estimate the prognosis of pterygium after resection. Afterward, a novel nomogram combined risk score of cytokines related biomarker and clinical characteristics was constructed, which manifested ideal accuracies to predict the 1 and 2 years' probability of pterygium recurrent events. Thus, our finding provides a more simple and accurate prediction for early pterygium recurrence after resection. It also affords a useful tool for ophthalmologists to choose the optimal treatment strategies for pterygium patients.

Geniposide attenuates postischemic long-term potentiation via GluN2A.

N-Methyl-D-aspartate receptor (NMDAR)-induced antioxidation is a significant cause of neuronal injury after ischemic stroke. In a previous work, we verified the neuroprotective roles of geniposide during tMCAO in vivo. However, it remains unknown whether geniposide ameliorates injury to hippocampal neurons during Ischemic Long Term Potentiation (iLTP) induction in vitro. After induction of cells oxygen-glucose deprivation or hydrogen peroxide, the protection of geniposide evaluated by MTT assay and electrophysiological tests. In this study, we suggested neuronal cell apoptosis was attenuated by geniposide. Furthermore, field excitatory postsynaptic potentials (fEPSCs) following postischemic LTP were assessed by electrophysiological tests. Finally, we determined that medium and high doses of geniposide attenuated oxidative stress insult and improved iLTP. Importantly, these effects were abolished by cotreatment with geniposide and the GluN2A antagonist NVP. In contrast, the GluN2B inhibitor ifenprodil failed to have an effect. In conclusion, we suggest for the first time that treatment with geniposide can attenuate postischemic LTP induction in a concentration-dependent manner. We infer that GluN2A-containing NMDARs are involved in the neuroprotection induced by geniposide treatment in ischemia.

Functional characterization of CEP250 variant identified in nonsyndromic retinitis pigmentosa.

Retinitis pigmentosa (RP) is the most common manifestation of inherited retinal diseases with high degree of genetic, allelic, and phenotypic heterogeneity. CEP250 encodes the C-Nap1 protein and has been associated with various retinal phenotypes. Here, we report the identification of a mutation (c.562C>T, p.R188*) in the CEP250 in a consanguineous family with nonsyndromic RP. To gain insights into the molecular pathomechanism underlying CEP250 defects and the functional relevance of CEP250 variants in humans, we conducted a functional characterization of CEP250 variant using a novel Cep250 knockin mouse line. Remarkably, the disruption of Cep250 resulted in severe impairment of retinal function and significant retinal morphological alterations. The homozygous knockin mice showed significantly reduced retinal thickness and ERG responses. This study not only broadens the spectrum of phenotypes associated with CEP250 mutations, but also, for the first time, elucidates the function of CEP250 in photoreceptors using a newly established animal model.

The association between plasma osmolality and in-hospital mortality in the first 24†h after neonatal intensive care unit admission.

Background: Perturbation of osmolality is associated with increased mortality in adults and children in critically ill conditions. However, it is still unclear whether osmolality imbalance impacts the prognosis of critically ill infants. This study aimed to investigate the relationship between plasma osmolality and prognosis in critically ill infants within 24 h of admission. Methods: This retrospective study enrolled 1,042 infants who had plasma osmolality data from 2010 to 2018. The initial plasma osmolality (within 24 h after admission) was extracted from the pediatric intensive care database (PIC V1.1). The locally weighted scatter-plot smoothing (LOWESS) and restricted cubic splines (RCS) methods were used to explore the approximate relationship between plasma osmolality and in-hospital mortality. Univariate and multivariate logistic regression analyses were used to further analyse this relationship. Kaplan-Meier analysis was applied to estimate the probability of hospital mortality within 90 days of admission. Subgroup analysis was employed to assess the impact of potential confounders (including postnatal days, gender, and gestational age). Results: An approximately"U"-shaped relationship between plasma osmolality and mortality was detected. In the logistic regression model, plasma osmolality <270 mmol/L (low osmolality group) was significantly associated with in-hospital mortality (P < 0.05; OR 2.52; 95% CI, 1.15-5.06). Plasma osmolality >300 mmol/L (high osmolality group) was also significantly associated with mortality (P < 0.05; OR 3.52; 95% CI, 1.16-8.83). This association remained even after multivariable adjustments. The 90-day survival rate was lower in the abnormal plasma osmolality group (including high or low osmolality groups) than in the intermediate group (log-rank test, P < 0.05). The abnormal plasma osmolality group had a significantly higher incidence of all-cause mortality in the 0-7 postnatal days subgroup (high osmolality group, P < 0.05; OR 5.25; low osmolality group, P < 0.05; OR 3.01). Infants with abnormal osmolality had a significantly higher mortality rate in the female group (P < 0.05). High osmolality was associated with a higher mortality rate in the preterm group (P < 0.05). Conclusions: Both hypoosmolality and hyperosmolality were shown to be independently associated with increased risk of in-hospital infant mortality in NICUs.

Ocular biometric parameters of mild hyperopia to mild myopia children aged 6-14 years from Wenzhou optometry center: A cross-sectional study.

Introduction: Myopia is the most common visual disorder in school-aged children and adolescents worldwide. This study aimed to explore the ocular biometric characteristics of children aged 6-14 years from the Wenzhou optometry center and to determine the relationship between spherical equivalent refraction (SER) and macular pigment optical density (MPOD). Subjects and methods: Participants underwent a full-scale ophthalmic examination anteriorly and posteriorly. Relevant parameters were documented, such as axial length (AL), anterior chamber depth (ACD), SER and lens thickness (LT), corneal curvature radius (CCR), and MPOD. Lens power (LP) was calculated using Bennett's formula. Shapiro-Wilk tests and histograms were used to check the normality of the distribution of refractive and ocular biometric parameters. Scatter diagrams were adopted to analyze the relationships between refraction and parameters of ocular biometry. Multiple linear regression models were employed to fit the associated factors of AL, AL/CCR, and LP. Results: A total of 902 mild hyperopia to mild myopia (+3.00 D ≤ SE ≤ -3.00 D) children aged 6-14 years were included. The mean age of participants was 10.03 ± 2.47 years, and the prevalence of mild hyperopia, emmetropia, and myopia was 5.65, 27.05, and 67.30%, respectively. The prevalence of mild myopia increased from 30.53% at 6 years of age to 93.62% at 14 years of age. Overall, AL, ACD, and AL/CCR increased, but LP declined from 6 to 14 years of age, whereas CCR and MPOD remained stable. An increase of 1 mm in AL was associated with -0.69 D of myopic change. A unit increase in AL/CCR was associated with -7.87 D in SER. As for the SER variance, AL explained 30.5% and AL/CCR explained 51.1%, whereas AL/CCR and LP accounted for 59.2%. Discussion: In this work, we have studied the distributions of ocular biometric characteristics of mild hyperopia to mild myopia children from the perspective of an optometry center rather than a sampling survey. In addition, we found that children from the optometry center had a slower progression toward myopia than those from previous sampling surveys, which was an informative finding for future myopia prevention. In addition, we have made a correlation analysis between the macular pigment optical density and spherical equivalent refraction. Though, no correlation was found.

Network Pharmacology and Pharmacological Mechanism of CV-3 in Atrial Fibrillation.

The high fatality and disability rate of atrial fibrillation (AF) strongly promote the development of pathogenesis and treatment of AF that is of great value. The present research attempted to clarify potential mechanisms of Mujiangzi oil (CV-3) in treating AF by constructing an AF cardiomyocytes model and using a network pharmacology approach. The experiment was divided into 4 groups: control, an AF model, AF + CV-3-treated, and the AF + verapamil group. Flow cytometry and the MTT assay were employed to detect cell apoptosis and cell viability, respectively. The main active components of CV-3 and predicted targets were obtained firstly, and molecular docking was performed. In the AF model, the cell apoptosis was aggravated, but inhibited in the CV-3-treated group. In addition, the cell viability was recovered after CV-3 treatment compared with the model group. Five potential active compounds of CV-3 were collected, including effective ingredients N-decanoic acid, spathulenol, copaene, ß-panasinsene, and eucalyptol. Among them, N-decanoic acid and spathulenol was demonstrated to bind to PTGS2 with binding energy of -4.08 and -7.09 kcal/mol, respectively, and hydrogen bonds interaction were found. The present study indicated that CV-3 could alleviate AF cardiomyocytes apoptosis and improve cardiomyocytes viability, and N-decanoic acid and spathulenol may be the key components of CV-3 in treatment of AF by regulating PTGS2. This study provided the possible target PTGS2 and the understanding of molecular mechanisms of CV-3 in treating AF.

Impact of the COVID-19 pandemic on neonatal admissions in a tertiary children's hospital in southwest China: An interrupted time-series study.

BACKGROUND: The unprecedented coronavirus disease 2019 (COVID-19) pandemic has caused millions of infections worldwide and represents a significant challenge facing modern health care systems. This study was conducted to investigate the impact of lockdown measures in a tertiary Children's Hospital in southwest China, which might be used to predict long-term effects related to health-seeking behavior of parents/caregivers. METHODS: This study included newborns enrolled over a span of 86 weeks between January 4, 2019, and August 27, 2020. We designated two time periods for analysis purposes: a stable pre-COVID period(55 weeks between January 4, 2019, and January 23, 2020) and a COVID-impacted period (31 weeks between January 24, 2020, and August 27, 2020). An interrupted time-series analysis was employed to compare changes and trends in hospital admissions and disease spectra before and after the period of nonpharmaceutical interventions (NPIs). Furthermore, this study was conducted to evaluate whether the health-seeking behavior of parents/caregivers was influenced by pandemic factors. RESULTS: Overall, 16,640 infants were admitted to the neonatology department during the pre-COVID period (n = 12,082) and the COVID-impacted period (n = 4,558). The per week neonatal admissions consistently decreased following the first days of NPIs (January 24, 2020). The average weekly admission rates of 220/week pre-COVID period and 147/week COVID-impacted period. There was an evident decrease in the volume of admissions for all disease spectra after the intervention, whereas the decrease of patients complaining about pathological jaundice-related conditions was statistically significant (p<0.05). In the COVID-impacted period, the percentage of patients who suffered from respiratory system diseases, neonatal encephalopathy, and infectious diseases decreased, while the percentage of pathological jaundice-related conditions and gastrointestinal system diseases increased. The neonatal mortality rates (NMRs) increased by 8.7% during the COVID-impacted period compared with the pre-COVID period. CONCLUSIONS: In summary, there was a significant decline in neonatal admissions in a tertiary care hospital during the COVID-19 Pandemic and the associated NPIs. Additionally, this situation had a remarkable impact on disease spectra and health-seeking behavior of parents/caregivers. We, therefore, advise continuing follow-ups and monitoring the main health indicators in vulnerable populations affected by this Pandemic over time.

Hypoxia-Immune-Related Gene SLC19A1 Serves as a Potential Biomarker for Prognosis in Multiple Myeloma.

Background: Multiple myeloma (MM) remains an incurable malignant tumor of plasma cells. Increasing evidence has reported that hypoxia and immune status contribute to the progression of MM. In this research, the prognostic value of the hypoxia-immune-related gene SLC19A1 in MM was evaluated by bioinformatics analysis. Method: RNA-sequencing (RNA-seq) data along with clinical information on MM were downloaded from the Gene Expression Omnibus (GEO) database. Consistent clustering analysis and ESTIMATE algorithms were performed to establish the MM sample subgroups related to hypoxia and immune status, respectively, based on the GSE24080 dataset. The differentially expressed analysis was performed to identify the hypoxia-immune-related genes. Subsequently, a hypoxia-immune-gene risk signature for MM patients was constructed by univariate and multivariate Cox regression analyses, which was also verified in the GSE4581 dataset. Furthermore, the mRNA expression of SLC19A1 was determined using qRT-PCR in 19 MM patients, and the correlations between the genetic expression of SLC19A1 and clinical features were further analyzed. Result: A total of 47 genes were identified as hypoxia-immune-related genes for MM. Among these genes, SLC19A1 was screened to construct a risk score model that had better predictive power for MM. The constructed prognostic signature based on SLC19A1 was verified in the GSE4581 dataset. All independent prognostic factors (age, ß2-microglobulin, LDH, albumin, MRI, and gene risk score) were used to develop a nomogram that showed a better performance for predicting the survival probability of MM patients for 1-5 years. Furthermore, SLC19A1 was highly expressed in newly diagnosed and relapsed MM patients, and high expression of SLC19A1 is correlated with higher bone marrow aspiration plasma cells and ß2-microglobulin levels in MM patients. Conclusion: In conclusion, our results suggest that SLC19A1 is aberrantly expressed in MM and highly expressed SLC19A1 might be a biomarker correlated with inferior prognosis. More importantly, we identified SLC19A1 as a hypoxia-immune-related gene in MM. Future functional and mechanistic studies will further clarify the roles of SLC19A1 in MM.

Osteopontin-integrin signaling positively regulates neuroplasticity through enhancing neural autophagy in the peri-infarct area after ischemic stroke.

OBJECTIVE: To investigate the role of Osteopontin (OPN) in mediating macroautophagy, autophagy, and neuroplasticity in the ipsilateral hemisphere after stroke. METHODS: Focal stroke was induced by photothrombosis in adult mice. Spatiotemporal expression of endogenous OPN and BECN1 was assessed by immunohistochemistry. Motor function was determined by the grid-walking and cylinder tasks. We also evaluated markers of neuroplasticity and autophagy using biochemical and histology analyses. RESULTS: Herein, we showed that endogenous OPN and beclin1 were increased in the peri-infarct area of stroked patients and mice. Intracerebral administration of OPN (0.1 mg/ml; 3 ml) significantly improved performance in motor behavioral tasks compared with non-OPN-treated stroke mice. Furthermore, the neural repair was induced in OPN-treated stroke mice. We found that OPN treatment resulted in a significantly higher density of a presynaptic marker (vesicular glutamate transporter 1, VgluT1) and synaptic plasticity marker (synaptophysin, SYN) within the peri-infarct region. OPN treatment in stroke mice not only increased protein levels of integrin ß1 but also promoted the expression of beclin1 and LC3, two autophagy-related proteins in the peri-infarct area. Additionally, OPN-induced neuroplasticity and autophagy were blocked by an integrin antagonist. CONCLUSION: Our findings indicate that OPN may enhance neuroplasticity via autophagy, providing a new therapeutic strategy for ischemic stroke.

Effect of neonatal neuronal intensive care unit on neonatal encephalopathy.

Prophylaxis of brain injury in newborns has been a main concern since the first neonatal neuronal intensive care unit (NNICU) was established in the world in 2008. The aim of this study was to outline and evaluate the unit's development by analyzing the demographics of the patients, the services delivered, the short-term outcomes before and after the establishment of NNICU. During the two investigation periods, 384 newborns were diagnosed or suspected as "neonatal encephalopathy", among which 185 patients admitted to NNICU between 2011.03.01 and 2012.09.30 before the establishment of NNICU were enrolled in the pre-NNICU group, another 199 neonates hospitalized during 2018.03.01 to 2019.09.30 were included in the post-NNICU group. Patients in the post-NNICU group were more likely to have seizures (P = 0.001), incomplete or absent primitive reflexes (P = 0.002), therapeutic hypothermia (P<0.001) and liquid control (P<0.001) in acute phase. Meanwhile, amplitude-integrated electro encephalogram (aEEG) monitoring (P<0.001) and cranial ultrasound (P<0.001) were more often used in NNICU. Both of the follow-up rate in brain MRI and the assessment of neurodevelopment at 3 months were higher in the post-NNICU group (P<0.001). In conclusion, the NNICU focused on the neonatal neurocritical care for the babies susceptible to NE with the guidance of evidence-based medicine, the establishment of NNICU is gradually improving and standardizing the neuroprotective therapy and clinical follow-up to improve neurodevelopmental prognosis of the NE patients in CHCMU.

A systematic review and meta-analysis to compare the efficacy of conbercept with ranibizumab in patients with macular edema secondary to retinal vein occlusion.

BACKGROUND: The objective of this review and meta-analysis is to investigate the efficacy of conbercept and ranibizumab, combined with or without laser photocoagulation, in patients with macular edema secondary to retinal vein occlusion (RVO-ME). METHODS: Several databases have been used to identify relevant publications. After screening, a meta-analysis was conducted to compare conbercept and ranibizumab with the support of RevMan 5.3 (Cochrane Library Software, Oxford, UK). RESULTS: In this study, 9 randomized controlled trials and 6 retrospective trials were included with a total of 1180 patients. No significant difference was found in best corrected visual acuity (BCVA) or central macular thickness (CMT) in the baseline parameters [BCVA (weighted mean difference (WMD): -0.01; 95% confidence interval CI: -0.03 to 0.01; P = .17), CMT (WMD: 20.14; 95% CI: -26.70 to 66.97; P = .40). No significant differences were found in the improvements of BCVA and adverse events (AEs) between the 2 groups after injection of loading dosage [the 1st month BCVA (WMD: -0.01; 95% CI: -0.04 to 0.02; P = .54),the 3rd month BCVA (WMD: -0.02; 95% CI: --0.05 to 0.01; P = .23), the 6th month BCVA (WMD: -0.02; 95% CI: -0.05 to 0.01; P = .27), AEs (odds ratio: 0.84; 95% CI: 0.38 to 1.84; P = .66)]. However, there were significant differences between conbercept and ranibizumab treatment in terms of CMT [1st month CMT (WMD: -11.70; 95% CI: -19.71 to -3.68; P < .01), 3rd month CMT (WMD: -10.08; 95% CI: -15.62 to -4.53; P < .01), 6th month CMT (WMD: -15.83; 95% CI: -22.88 to -8.78; P < .01)] and the number of injections (WMD, -0.36; 95% CI: -0.68 to -0.04; P = .03). CONCLUSION: The current pooled evidence suggested that both therapies of intravitreal conbercept and intravitreal ranibizumab with or without laser photocoagulation are effective in vision function in RVO-ME patients, and confirmed that conbercept has advantages over ranibizumab in terms of CMT and the number of injections for treating RVO-ME. In addition, conbercept has the statistically same visual gains and safety as ranibizumab in RVO-ME patients. Longer-term follow-up surveys on the safety and effectiveness of these 2 treatment regimens are required.

Discovery and Validation of a Metastasis-Related Prognostic and Diagnostic Biomarker for Melanoma Based on Single Cell and Gene Expression Datasets.

BACKGROUND: Single cell sequencing can provide comprehensive information about gene expression in individual tumor cells, which can allow exploration of heterogeneity of malignant melanoma cells and identification of new anticancer therapeutic targets. METHODS: Single cell sequencing of 31 melanoma patients in GSE115978 was downloaded from the Gene Expression Omniniub (GEO) database. First, the limma package in R software was used to identify the differentially expressed metastasis related genes (MRGs). Next, we developed a prognostic MRGs biomarker in the cancer genome atlas (TCGA) by combining univariate cox analysis and the least absolute shrinkage and selection operator (LASSO) method and was further validated in another two independent datasets. The efficiency of MRGs biomarker in diagnosis of melanoma was also evaluated in multiple datasets. The pattern of somatic tumor mutation, immune infiltration, and underlying pathways were further explored. Furthermore, nomograms were constructed and decision curve analyses were also performed to evaluate the clinical usefulness of the nomograms. RESULTS: In total, 41 MRGs were screened out from 1958 malignant melanoma cell samples in GSE115978. Next, a 5-MRGs prognostic marker was constructed and validated, which show more effective performance for the diagnosis and prognosis of melanoma patients. The nomogram showed good accuracies in predicting 3 and 5 years survival, and the decision curve of nomogram model manifested a higher net benefit than tumor stage and clark level. In addition, melanoma patients can be divided into high and low risk subgroups, which owned differential mutation, immune infiltration, and clinical features. The low risk subgroup suffered from a higher tumor mutation burden (TMB), and higher levels of T cells infiltrating have a significantly longer survival time than the high risk subgroup. Gene Set Enrichment Analysis (GSEA) revealed that the extracellular matrix (ECM) receptor interaction and epithelial mesenchymal transition (EMT) were the most significant upregulated pathways in the high risk group. CONCLUSIONS: We identified a robust MRGs marker based on single cell sequencing and validated in multiple independent cohort studies. Our finding provides a new clinical application for prognostic and diagnostic prediction and finds some potential targets against metastasis of melanoma.

Prognostic Value of Clinical Tests in Neonates With Hypoxic-Ischemic Encephalopathy Treated With Therapeutic Hypothermia: A Systematic Review and Meta-Analysis.

Background and Objective: There remains an unmet clinical need for markers that predict outcomes in the hypothermia-treated (HT) infants with HIE. The aim of this meta-analysis was to investigate the prognostic accuracy of currently available clinical tests performed in the immediate post-natal period for predicting neurological outcomes between 18 months and 3 years of age in HT near-term and term infants with perinatal asphyxia and HIE. Methods: A comprehensive review of the Embase, Cochrane library, and PubMed databases was performed to identify studies that evaluated the prognostic value of clinical tests for neurological outcomes in HT near-term and term infants with perinatal asphyxia and hypoxic-ischemic encephalopathy. Pooled sensitivity and specificity with corresponding 95% confidence intervals and area under the receiver operating characteristic (ROC) curve (AUC) were calculated. Results: Of the 1,144 relevant studies, 26 studies describing four clinical tests conducted in 1458 HT near-term or term infants were included. For predicting an unfavorable neurological outcome, of the imaging techniques, MRI within 2 weeks of birth performed best on sensitivity 0.85 (95% CI 0.79-0.89), specificity 0.72 (95% CI 0.66-0.77), and AUC 0.88; among the neurophysiological tests, multichannel EEG (Electroencephalogram) demonstrated the sensitivity 0.63 (95% CI 0.49-0.76), specificity 0.82 (95% CI 0.70-0.91), and AUC 0.88, and for aEEG (amplitude-integrated electroencephalography) background pattern pooled sensitivity, specificity and AUC were 0.90 (95% CI 0.86-0.94), 0.46 (95% CI 0.42-0.51), and 0.78 whereas for SEPs (Somatosensory evoked potentials), pooled sensitivity and specificity were 0.52 (95% CI 0.34-0.69), 0.76 (95% CI 0.63-0.87), and AUC 0.84, respectively. Conclusions: In the wake of the era of TH, MRI and neurophysiological tests (aEEG or EEG) were promising predictors of adverse outcomes, while SEPs need high-quality studies to confirm the findings. Continued follow-up of the children and well-designed large prospective studies are essential to determine whether these benefits are maintained in later childhood.

Topographic distribution features of the choroidal and retinal nerve fiber layer thickness in Wenzhou school-aged children.

AIM: To explore the topographic distribution features of choroidal thickness (CT) and retinal nerve fiber layer thickness (RNFLT), and determine the relationship between CT and ocular parameters in school-aged children. METHODS: The healthy school-aged children with low myopia or emmetropia in Wenzhou were recruited for this cross-sectional study. With high-density optical coherence tomography (HD-OCT) combined with MATLAB software, the CT and RNFLT values in the macular area were measured at different locations and compared. Statistical analyses were performed to evaluate the correlation between CT and ophthalmic parameters, such as spherical equivalent (SE) and the axial length (AL). RESULTS: A total of 279 school-aged children with 8.00±1.35 years of mean age (range, 6-10y) were included. The mean AL was 23.66±0.86 mm. The mean CT in CT-C (264.31±48.93 µm) was thicker than that in CT-N1 (249.54±50.52 µm), and the average CT in the parafoveal region was also thicker than that in CT-N2 (235.65±50.63 µm). The subfoveal CT also varied substantially across refractive errors (P<0.001), and those with myopia (250.59±47.01 µm) exhibited a thinner choroid compared with those with emmetropia (278.74±48.06 µm). CT positively correlated with AL (y=11.12x-4.15; R 2=0.18), and positively correlated with SE (y=90.07x+17.916; R 2=14.2). The average RNFLT was thickest in the peripapillary region (236.35±19.03 µm), the mean RNFLT-S (131.10±15.16 µm) was thicker than the RNFLT-I (128.20±16.59 µm), and the mean RNFLT-T (76.54±11.99 µm) was thicker than the RNFLT-N (64.28±8.55 µm). The variations in the RNFLT between quadrants did differ between those with myopia and emmetropia (P<0.05). CONCLUSION: We establish demographic information for the choroid and RNFLT. These findings provide information that should be considered in future analyses of the CT and RNFLT in OCT studies in school-aged children.

Glycine attenuates cerebrovascular remodeling via glycine receptor alpha 2 and vascular endothelial growth factor receptor 2 after stroke.

As a dual-acting neurotransmitter, glycine plays critical roles in cerebral ischemia by activating both glycine receptors (GlyRs) and N-methyl-D-aspartate acid receptors (NMDARs). However, the involvement of glycine receptor alpha 2 (GlyRa2) in cerebral ischemia has not been explored. The objective of this study was to determine the mechanism of action of GlyRa2 in cerebrovascular remodeling. After induction of rat tMCAO, levels of the GLRA2 gene and GlyRa2 protein were examined using q-PCR, western blot, and immunohistochemical analyses. Blood-brain barrier permeability, and the presence of hemorrhage and arteriosclerosis were also analyzed. The underlying mechanism of vascular remodeling was examined using immunohistochemical and immunofluorescence analyses. Both the GLRA2 gene and GlyRa2 protein were altered sharply after stroke. GlyRa2 of vascular origin appears to play a protective role after glycine treatment for ischemia. Blockade of GlyRa2 by the addition of cyclothiazide was found to abolish previous improvements in cerebrovascular survival after glycine treatment for tMCAO in rats. GlyRa2-dependent neurovascular remodeling was found to be correlated with the vascular endothelial growth factor receptor 2 (VEGFR2) pathways. These results suggest that vascular-derived GlyRa2 protects against post-ischemic injury. Vascular protection via GlyRa2 is due to VEGFR2/pSTAT3 signaling.

Topographic distribution features of the choroidal and retinal nerve fiber layer thickness in Chinese school-aged children.

AIM: To explore the topographic distribution features of choroidal thickness (CT) and retinal nerve fiber layer thickness (RNFLT), and determine the relationship between CT and ocular parameters in school-aged children. METHODS: The healthy school-aged children with low ametropia or emmetropia in Wenzhou were recruited for this cross-sectional study. With high-density optical coherence tomography (HD-OCT) combined with MATLAB software, the CT and RNFLT values in the macular area were measured at different locations and compared. Statistical analyses were performed to evaluate the correlation between CT and ophthalmic parameters, such as spherical equivalent (SE) and the axial length (AL). RESULTS: A total of 279 school-aged children with 8.00±1.35 years of mean age (range, 6-10y) were included. The mean AL was 23.66±0.86 mm. The mean CT in CT-C (264.31±48.93 µm) was thicker than that in CT-N1 (249.54±50.52 µm), and the average CT in the parafoveal region was also thicker than that in CT-N2 (235.65±50.63 µm). The subfoveal CT also varied substantially across refractive errors (P<0.001), and those with myopia (250.59±47.01 µm) exhibited a thinner choroid compared with those with emmetropia (278.74±48.06 µm). CT negatively correlated with AL (y=-21.72x+779.17; R 2=0.1458), and positively correlated with SE (y=15.76x+271.9; R 2=0.0727, OD; y=18.31x+269.8; R 2=0.1007, OS). The average RNFLT was thickest in the peripapillary region (236.35±19.03 µm), the mean RNFLT-S (131.10±15.16 µm) was thicker than the RNFLT-I (128.20±16.59 µm), and the mean RNFLT-T (76.54±11.99 µm) was thicker than the RNFLT-N (64.28±8.55 µm). The variations in the RNFLT between quadrants did differ between those with myopia and emmetropia (P<0.05). CONCLUSION: We establish demographic information for the choroid and RNFLT. These findings provide information that should be considered in future analyses of the CT and RNFLT in OCT studies in school-aged children.