The Roles of Circular RNAs in Ischemic Stroke through Modulating Neuroinflammation.

Ischemic stroke (IS) remains a serious threat to human health. Neuroinflammatory response is an important pathophysiological process after IS. Circular RNAs (circRNAs), a member of the non-coding RNA family, are highly expressed in the central nervous system and widely involved in regulating physiological and pathophysiological processes. This study reviews the current evidence on neuroinflammatory responses, the role of circRNAs in IS and their potential mechanisms in regulating inflammatory cells, and inflammatory factors affecting IS damage. This review lays a foundation for future clinical application of circRNAs as novel biomarkers and therapeutic targets.

Role of Circular RNAs in Atherosclerosis through Regulation of Inflammation, Cell Proliferation, Migration, and Apoptosis: Focus on Atherosclerotic Cerebrovascular Disease.

Atherosclerosis (AS) is a disease dangerous to human health and the main pathological cause of ischemic cardiovascular diseases. Although its pathogenesis is not fully understood, numerous basic and clinical studies have shown that AS is a chronic inflammatory disease existing in all stages of atherogenesis. It may be a common link or pathway in the pathogenesis of multiple atherogenic factors. Inflammation is associated with AS complications, such as plaque rupture and ischemic cerebral infarction. In addition to inflammation, apoptosis plays an important role in AS. Apoptosis is a type of programmed cell death, and different apoptotic cells have different or even opposite roles in the process of AS. Unlike linear RNA, circular RNA (circRNA) a covalently closed circular non-coding RNA, is stable and can sponge miRNA, which can affect the stages of AS by regulating downstream pathways. Ultimately, circRNAs play very important roles in AS by regulating inflammation, apoptosis, and some other mechanisms. The study of circular RNAs can provide new ideas for the prediction, prevention, and treatment of AS.

Effectiveness of feeding supplementation in preterm infants: an overview of systematic reviews.

BACKGROUND: Preterm infants have higher nutrition needs than term infants. The effectiveness of various feeding supplementation was assessed by the improvement of health outcomes in single specific systematic reviews (SRs). The aim of this review was to comprehensively describe the effectiveness of feeding supplementation in promoting health outcomes of preterm infants. METHODS: A literature search was conducted in the PUBMED, EMBASE, Science Direct, Cochrane library, Web of Science, and Wiley online library. SRs selection followed clear inclusion and exclusion criteria. Pairs of reviewers independently applied the criteria to both titles/abstracts and full texts. Screening and data extraction were performed by using the advanced tables. The methodological quality of SRs and the quality of the evidence were carried out according to the Assessing the Methodological Quality of Systematic Reviews (AMSTAR) tool and the Grades of Recommendation, Assessment, Development, and Evaluation guidelines (GRADE) respectively. A qualitative synthesis of evidence is presented. RESULTS: Seventeen SRs were included in the review. Fifteen kinds of feeding supplementation were reported in the SRs. In preterm infants, the effectiveness of feeding supplementation in addition to regular breast-feeding was mainly shown in six aspects: physical health, neurodevelopment, biochemical outcomes, other health outcomes, morbidity and all-cause mortality. And the effectiveness of the interventions on health outcomes in preterm infants was found by most systematic reviews. The methodological quality of all the included SRs was high, and most of the evidences was of low or very low quality. CONCLUSIONS: Our results will allow a better understanding of the feeding supplementation in preterm infants. Although the feeling supplements may improve the health outcomes of in preterm infants, the existing evidence is uncertain. Therefore, the clinical use of these supplements should be considered cautiously and more well-designed RCTs are still needed to further address the unsolved problems of the included SRs.

The influence of coronavirus disease 2019 on emergency department visits in Nanjing, China: A multicentre cross-sectional study.

INTRODUCTION: Influenza has been linked to the crowding in emergency departments (ED) across the world. The impact of the Coronavirus Disease 2019 (COVID-19) pandemic on China EDs has been quite different from those during past influenza outbreaks. Our objective was to determine if COVID-19 changed ED visit disease severity during the pandemic. METHODS: This was a retrospective cross sectional study conducted in Nanjing, China. We captured ED visit data from 28 hospitals. We then compared visit numbers from October 2019 to February 2020 for a month-to-month analysis and every February from 2017 to 2020 for a year-to-year analysis. Inter-group chi-square test and time series trend tests were performed to compare visit numbers. The primary outcome was the proportion of severe disease visits in the EDs. RESULTS: Through February 29 th 2020, there were 93 laboratory-confirmed COVID-19 patients in Nanjing, of which 40 cases (43.01%) were first seen in the ED. The total number of ED visits in Nanjing in February 2020, were dramatically decreased (n = 99,949) in compared to January 2020 (n = 313,125) and February 2019 (n = 262,503). Except for poisoning, the severe diseases in EDs all decreased in absolute number, but increased in proportion both in year-to-year and month-to-month analyses. This increase in proportional ED disease severity was greater in higher-level referral hospitals when compared year by year. CONCLUSION: The COVID-19 outbreak has been associated with decreases in ED visits in Nanjing, China, but increases in the proportion of severe ED visits.

Interfacial redox processes in memristive devices based on valence change and electrochemical metallization.

Memristive devices based on electrochemical processes are promising candidates for next-generation memory and neuromorphic applications. The redox processes happening at the interfaces are crucial steps for the ionization as well as generation of counter charges, and are thus indispensable for successful resistive switching, but their detailed mechanism has not been fully clarified. Here, we study the interfacial redox reactions in the forming process of memristive devices based on valence change and electrochemical metallization, using high-resolution electron microscopy and electrostatic force microscopy observations. We show direct evidence for the anodic oxidation of oxygen ions and cathodic reduction of moisture in HfO2- and Ta2O5-based valence change cells, which could take place in different horizontal locations. We further found that the anodic reactions always led to more pronounced structural damage to the electrode, indicating the possibility of additional cathodic reactions without producing gaseous products. When an active electrode is present, oxidation of metal atoms takes place at the anodic interface instead. Further investigations on electrochemical metallization cells have identified Cu ionization and moisture reduction as the anodic and cathodic reactions, respectively, and formation of Cu nuclei at the cathodic interface was directly observed. These findings with microscopic evidence could facilitate future development of memristive devices.

Annotating function to differentially expressed LincRNAs in myelodysplastic syndrome using a network-based method.

MOTIVATION: Long non-coding RNAs (lncRNAs) have been implicated in the regulation of diverse biological functions. The number of newly identified lncRNAs has increased dramatically in recent years but their expression and function have not yet been described from most diseases. To elucidate lncRNA function in human disease, we have developed a novel network based method (NLCFA) integrating correlations between lncRNA, protein coding genes and noncoding miRNAs. We have also integrated target gene associations and protein-protein interactions and designed our model to provide information on the combined influence of mRNAs, lncRNAs and miRNAs on cellular signal transduction networks. RESULTS: We have generated lncRNA expression profiles from the CD34+ haematopoietic stem and progenitor cells (HSPCs) from patients with Myelodysplastic syndromes (MDS) and healthy donors. We report, for the first time, aberrantly expressed lncRNAs in MDS and further prioritize biologically relevant lncRNAs using the NLCFA. Taken together, our data suggests that aberrant levels of specific lncRNAs are intimately involved in network modules that control multiple cancer-associated signalling pathways and cellular processes. Importantly, our method can be applied to prioritize aberrantly expressed lncRNAs for functional validation in other diseases and biological contexts. AVAILABILITY AND IMPLEMENTATION: The method is implemented in R language and Matlab. CONTACT: xizhou@wakehealth.edu. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Mutation status coupled with RNA-sequencing data can efficiently identify important non-significantly mutated genes serving as diagnostic biomarkers of endometrial cancer.

BACKGROUND: Endometrial cancers (ECs) are one of the most common types of malignant tumor in females. Substantial efforts had been made to identify significantly mutated genes (SMGs) in ECs and use them as biomarkers for the classification of histological subtypes and the prediction of clinical outcomes. However, the impact of non-significantly mutated genes (non-SMGs), which may also play important roles in the prognosis of EC patients, has not been extensively studied. Therefore, it is essential for the discovery of biomarkers in ECs to further investigate the non-SMGs that were highly associated with clinical outcomes. RESULTS: For the 9681 non-SMGs reported by the mutation annotation pipeline, there were 1053, 1273 and 395 non-SMGs differentially expressed between the patient groups divided by the clinical endpoints of histological grade, histological type as well as the International Federation of Gynecology and Obstetrics (FIGO) stage of ECs, respectively. In the gene set enrichment analysis, the cancer-related pathways, namely neuroactive ligand-receptor interaction signaling pathway, cAMP signaling pathway and calcium signaling pathway, were significantly enriched with the differentially expressed non-SMGs for all the three endpoints. We further identified 23, 19 and 24 non-SMGs, which were highly associated with histological grade, histological type and FIGO stage, respectively, from the differentially expressed non-SMGs by using the variable combination population analysis (VCPA) approach and found that 69.6% (16/23), 78.9% (15/19) and 66.7% (16/24) of the identified non-SMGs had been previously reported to be correlated with cancers. In addition, the averaged areas under the receiver operating characteristic curve (AUCs) achieved by the predictive models with identified non-SMGs as predictors in predicting histological type, histological grade, and FIGO stage were 0.993, 0.961 and 0.832, respectively, which were superior to those achieved by the models with SMGs as features (averaged AUCs = 0.928, 0.864 and 0.535, resp.). CONCLUSIONS: Besides the SMGs, the non-SMGs reported in the mutation annotation analysis may also involve the crucial genes that were highly associated with clinical outcomes. Combining the mutation status with the gene expression profiles can efficiently identify the cancer-related non-SMGs as predictors for cancer prognostic prediction and provide more supplemental candidates for the discovery of biomarkers.

Late recanalisation beyond 24 hours is associated with worse outcome: an observational study.

OBJECTIVES: We evaluated the rate of late recanalisation beyond 24 h after intravenous thrombolysis (IVT) and its relationship with haemorrhagic transformation and outcome. METHODS: We reviewed prospectively collected clinical and imaging data from acute ischaemic stroke patients with distal internal carotid artery or proximal middle cerebral artery occlusion who underwent angiography on admission, 24 h and 1 week after IVT. Patients were trichotomised according to vascular status: timely recanalisation (<24 h), late recanalisation (24 h-7 days), and no recanalisation. RESULTS: Non-invasive angiography revealed timely recanalisation in 52 (50.0 %) patients, late recanalisation in 25 (24.0 %) patients, and no recanalisation in 27 (26.0 %) patients. Pre-existing atrial fibrillation was associated with the occurrence of late recanalisation (odds ratio 6.674; 95 % CI: 1.197 to 37.209; p = 0.030). In patients without timely recanalisation, shift analysis indicated that late recanalisation led to a worse modified Rankin Scale score (odds ratio 6.787; 95 % CI: 2.094 to 21.978; p = 0.001). CONCLUSIONS: About half of all patients without recanalisation by 24 h after IVT may develop late recanalisation within 1 week, along with higher mRS scores by 3 months. Pre-existing atrial fibrillation is an independent predictor for late recanalisation. KEY POINTS: • About half of patients may develop late recanalisation within 1 week. • Pre-existing atrial fibrillation was associated with the occurrence of late recanalisation. • Late recanalisation led to a higher mRS score than no recanalisation.

Immune signaling-based Cascade Propagation approach re-stratifies HNSCC patients.

The availability of high-throughput genomic assays and rich electronic medical records allows us to identify cancer subtypes with greater accuracy and resolution. The integration of multiplatform, heterogenous, and high dimensional data remains an enormous challenge in using big data in bioinformatics research. Previous methods have been developed for patient stratification, however, these approaches did not incorporate prior knowledge and offer limited biology insight. New computational methods are needed to better utilize multiple types of information to identify clinically meaningful subtypes. Recent studies have shown that many immune functional genes are associated with cancer progression, recurrence and prognosis in head and neck squamous cell carcinoma (HNSCC). Therefore, we developed a novel immune signaling based Cascade Propagation (CasP) subtyping approach to stratify HNSCC patients. Unlike previous stratification methods that use only patient genomic data, our approach makes use of prior biological information such as immune signaling and protein-protein interactions, as well as patient survival information. CasP is a multi-step stratification procedure, composed of a dynamic network tree cutting step followed by a mutational stratification step. Using this approach, HNSCC patients were first stratified into clinically relative subgroups with different survival outcomes and distinct immunogenic features. We found that the good outcome of a subgroup of HNSCC patients was due to an enhanced immune response. The gene sets were characterized by a significant activation of T cell receptor signaling pathways, in addition to other important cancer related pathways such as PI3K and JAK/STAT signaling pathways. Further stratification of patients based on somatic mutation profiles detected three survival-distinct subnetworks. Our newly developed CasP subtyping approach allowed us to integrate multiple data types and identify clinically relevant subtypes of HNSCC patients.

Timing of Occurrence Is the Most Important Characteristic of Spot Sign.

BACKGROUND AND PURPOSE: Most previous studies have used single-phase computed tomographic angiography to detect the spot sign, a marker for hematoma expansion (HE) in spontaneous intracerebral hemorrhage. We investigated whether defining the spot sign based on timing on perfusion computed tomography (CTP) would improve its specificity for predicting HE. METHODS: We prospectively enrolled supratentorial spontaneous intracerebral hemorrhage patients who underwent CTP within 6 hours of onset. Logistic regression was performed to assess the risk factors for HE and poor outcome. Predictive performance of individual CTP spot sign characteristics were examined with receiver operating characteristic analysis. RESULTS: Sixty-two men and 21 women with spontaneous intracerebral hemorrhage were included in this analysis. Spot sign was detected in 46% (38/83) of patients. Receiver operating characteristic analysis indicated that the timing of spot sign occurrence on CTP had the greatest area under receiver operating characteristic curve for HE (0.794; 95% confidence interval, 0.630-0.958; P=0.007); the cutoff time was 23.13 seconds. On multivariable analysis, the presence of early-occurring spot sign (ie, spot sign before 23.13 seconds) was an independent predictor not only of HE (odds ratio=28.835; 95% confidence interval, 6.960-119.458; P<0.001), but also of mortality at 3 months (odds ratio =22.377; 95% confidence interval, 1.773-282.334; P=0.016). Moreover, the predictive performance showed that the redefined early-occurring spot sign maintained a higher specificity for HE compared with spot sign (91% versus 74%). CONCLUSIONS: Redefining the spot sign based on timing of contrast leakage on CTP to determine early-occurring spot sign improves the specificity for predicting HE and 3-month mortality. The use of early-occurring spot sign could improve the selection of ICH patients for potential hemostatic therapy.

Identifying cancer-related microRNAs based on gene expression data.

MOTIVATION: MicroRNAs (miRNAs) are short non-coding RNAs that play important roles in post-transcriptional regulations as well as other important biological processes. Recently, accumulating evidences indicate that miRNAs are extensively involved in cancer. However, it is a big challenge to identify which miRNAs are related to which cancer considering the complex processes involved in tumors, where one miRNA may target hundreds or even thousands of genes and one gene may regulate multiple miRNAs. Despite integrative analysis of matched gene and miRNA expression data can help identify cancer-associated miRNAs, such kind of data is not commonly available. On the other hand, there are huge amount of gene expression data that are publicly accessible. It will significantly improve the efficiency of characterizing miRNA's function in cancer if we can identify cancer miRNAs directly from gene expression data. RESULTS: We present a novel computational framework to identify the cancer-related miRNAs based solely on gene expression profiles without requiring either miRNA expression data or the matched gene and miRNA expression data. The results on multiple cancer datasets show that our proposed method can effectively identify cancer-related miRNAs with higher precision compared with other popular approaches. Furthermore, some of our novel predictions are validated by both differentially expressed miRNAs and evidences from literature, implying the predictive power of our proposed method. In addition, we construct a cancer-miRNA-pathway network, which can help explain how miRNAs are involved in cancer. AVAILABILITY AND IMPLEMENTATION: The R code and data files for the proposed method are available at http://comp-sysbio.org/miR_Path/ CONTACT: liukeq@gmail.com SUPPLEMENTARY INFORMATION: supplementary data are available at Bioinformatics online.

Lower serum calcium level is associated with hemorrhagic transformation after thrombolysis.

BACKGROUND AND PURPOSE: We aim to investigate whether lower admission serum calcium levels are associated with hemorrhagic transformation (HT) after intravenous thrombolysis (IVT). METHODS: A total of 362 patients treated with IVT was divided into 4 quartiles based on admission serum calcium levels (Q1[<2.16], Q2[2.16, 2.23], Q3[2.24, 2.31], and Q4[>2.31] mmol/L). HT was classified as hemorrhagic infarction and parenchymal hemorrhage. Logistic regression was applied to assess the association between serum calcium levels and the incidence of HT. RESULTS: Compared with Q4, HT was more common in Q1 (odds ratio, 2.580; 95% CI, [1.258-5.292]; P=0.010), Q2 (odds ratio, 2.382; 95% CI, [1.163-4.877]; P=0.018), and Q3 (odds ratio, 2.293; 95% CI, [1.133-4.637]; P=0.021). Hemorrhagic infarction was more common in Q1 (P=0.037), and Q2 (P=0.018), compared with Q4, and parenchymal hemorrhage was more common in Q1 (P=0.029) than Q4. CONCLUSIONS: Lower admission serum calcium level is independently associated with HT after IVT, and this hypothesis needs larger confirmatory trials.

[Relationship between early blood pressure variability and reperfusion in acute ischemic stroke patients with intravenous thrombolysis].

OBJECTIVE: To investigate the impacts of blood pressure (BP) variability on reperfusion and long-term outcome in patients with acute ischemic stroke after intravenous thrombolysis (IVT). METHODS: The clinical data of 188 patients with acute ischemic stroke receiving IVT in Department of Neurology, the Second Affiliated Hospital, Zhejiang University School of Medicine from June 2009 to September 2014, including hour-to-hour BP measurements, clinical manifestations, laboratory tests and radiologic findings were retrospectively analyzed. The mean 24-h BP values, and BP variability profiles, including standard deviation (sd), average squared difference between successive measurements (sv), average squared difference between rise and drop successive measurements (sv-rise and sv-drop) were calculated. Reperfusion, defined as >50% reduction in Tmax >6 s perfusion lesion volume from baseline to follow-up scans, and clinical neurological outcome based on modified Rankin scale (mRS) at 3 months after onset were also analyzed. The favorable outcome was defined as mRS 0-1 and unfavorable outcome as mRS 2-6. The binary logistic-regression model was performed to determine the independent risk factors of reperfusion and favorable outcome, respectively. RESULTS: Among 188 patients, 114 (60.6%) achieved reperfusion. During the 0-to-24 h blood pressure course, only systolic blood pressure (SBP) variability parameters were negatively correlated with reperfusion (sv: OR=0.421, 95% CI:0.187-0.950, P=0.037; sv-rise: OR=0.311, 95% CI:0.137-0.704, P=0.005) and long-term clinical outcomes (sv: OR=6.381, 95% CI:2.132-19.096, P=0.001; sv-rise: OR=5.615, 95% CI:2.152-14.654, P<0.001; sv-drop: OR=3.009, 95% CI:1.263-7.169, P=0.013). CONCLUSION: SBP variability during the first 24 hours after IVT is negatively associated with cerebral reperfusion and unfavorable neurological outcome in patients with acute ischemic stroke receiving IVT.

NARROMI: a noise and redundancy reduction technique improves accuracy of gene regulatory network inference.

MOTIVATION: Reconstruction of gene regulatory networks (GRNs) is of utmost interest to biologists and is vital for understanding the complex regulatory mechanisms within the cell. Despite various methods developed for reconstruction of GRNs from gene expression profiles, they are notorious for high false positive rate owing to the noise inherited in the data, especially for the dataset with a large number of genes but a small number of samples. RESULTS: In this work, we present a novel method, namely NARROMI, to improve the accuracy of GRN inference by combining ordinary differential equation-based recursive optimization (RO) and information theory-based mutual information (MI). In the proposed algorithm, the noisy regulations with low pairwise correlations are first removed by using MI, and the redundant regulations from indirect regulators are further excluded by RO to improve the accuracy of inferred GRNs. In particular, the RO step can help to determine regulatory directions without prior knowledge of regulators. The results on benchmark datasets from Dialogue for Reverse Engineering Assessments and Methods challenge and experimentally determined GRN of Escherichia coli show that NARROMI significantly outperforms other popular methods in terms of false positive rates and accuracy. AVAILABILITY: All the source data and code are available at: http://csb.shu.edu.cn/narromi.htm.

[Risk factors of hemorrhagic transformation in different locations and its relation to clinical outcomes of patients with acute ischemic stroke following intravenous thrombolysis].

OBJECTIVE: To investigate the risk factors of hemorrhagic transformation (HT) in different cerebral regions and to explore its relation to clinical outcomes of patients with acute ischemic stroke after intravenous thrombolysis therapy. METHODS: The clinical, laboratory, and radiological data of 292 consecutive acute ischemic stroke patients undergoing intravenous thrombolysis therapy in Second Affiliated Hospital, Zhejiang University School of Medicine from June 2009 to May 2013 was retrospectively analyzed. Deep HT was defined as HT located in basal ganglia, internal capsule, external capsule and thalamus, otherwise the lesion was defined as non-deep HT. Patients were divided into 3 groups [Deep HT(n=47), non-deep HT(n=82), non HT(n=8)] and the differences in clinical and demographic characteristics were compared by using one-way analysis of variance and Ξ2-test. Multivariable logistic regression models were used to determine the independent risk factors of HT in different cerebral regions and clinical outcomes. RESULTS: Age, baseline National Institutes of Health Stroke Scale (NIHSS) score, baseline systolic blood pressure and the frequency of atrial fibrillation were different among three groups. Logistic regression analysis revealed that baseline NIHSS score (OR=1.126, 95%CI:1.063-1.193, P<0.001) and baseline systolic blood pressure (OR=0.982, 95%CI:0.967-0.998, P=0.020) were independent risk factors of deep HT. Multivariate analysis also found that deep HT was an independent predictor of functional outcome after thrombolysis (OR=0.291, 95%CI:0.133-0.640, P=0.002). CONCLUSION: Baseline NIHSS score and systolic blood pressure are predictors for deep hemorrhagic transformation, which indicates the poor functional outcome of patients with acute ischemic stroke following thrombolytic therapy.

The association between prenatal exposure to bisphenol A and offspring obesity: A systematic review.

In recent years, the global prevalence of childhood overweight and obesity has surged. Bisphenol A (BPA), prevalent in the manufacture of polycarbonate plastics and epoxy resins, is associated with this escalating obesity pattern. Both early life stages and pregnancy emerge as pivotal windows of vulnerability. This review systematically evaluates human studies to clarify the nexus between prenatal BPA exposure and offspring obesity. Our extensive literature search covered databases like PubMed, Web of Science, Cochrane Library, Embase, and Scopus, encompassing articles from their inception until July 2023. We utilized the Newcastle-Ottawa Scale (NOS) to evaluate the methodological rigor of the included studies, the Oxford Center for Evidence-Based Medicine Levels of Evidence Working Group (OCEBM) table to determine the level of the evidence, and the Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) guidelines to evaluate the certainty of the evidence with statistical significance. We centered on primary studies investigating the link between urinary BPA levels during pregnancy and offspring obesity. Our analysis included thirteen studies, with participant counts ranging from 173 to 1124 mother-child dyads. Among them, eight studies conclusively linked prenatal BPA exposure to increased obesity in offspring. Evaluation metrics for the effect of prenatal BPA on offspring obesity comprised BMI z-score, waist circumference, overweight/obesity classification, aggregate skinfold thickness, body fat percentage, and more. Present findings indicate that prenatal BPA exposure amplifies offspring obesity risk, with potential effect variations by age and gender. Therefore, further research is needed to explore the causal link between prenatal BPA exposure and obesity at different developmental stages and genders, and to elucidate the underlying mechanisms.

Prenatal exposure to bisphenol A and neonatal health outcomes: A systematic review.

Bisphenol A (BPA) is an endocrine-disrupting chemical substance responsible for the composition of polycarbonate plastics and epoxy resins. Early life and pregnancy are important windows of susceptibility. This review aimed to conduct a systematic assessment of human studies to comprehensively describe the association between prenatal BPA exposure and neonatal health outcomes. Literature was searched in Cochrane Library, Embase, PubMed, Scopus, and Web of Science published before November 2022, and were selected according to clear inclusion and exclusion criteria. The Newcastle-Ottawa scale (NOS) and Grades of Recommendation, Assessment, Development, and Evaluation guidelines (GRADE) were followed to grade the methodological quality of studies and the certainty of the evidence respectively. As a result, a total of 22259 participants from 45 trials were included. And the potential associations of prenatal exposure to BPA and neonatal health outcomes were mainly shown in four aspects: gestational age/preterm birth, physical health at birth, the incidence of systemic abnormalities or diseases, and other health outcomes. Although the certainty of the evidence was low to very low, the methodological quality of the included studies was high. Prenatal BPA exposure tended to have negative effects on most of the health outcomes in neonates but showed inconsistent results on physical health at birth. This systematic review is the first to comprehensively synthesize the existing evidence on the association between prenatal BPA exposure and neonatal health outcomes. In the future, further studies are still needed to verify these effects and elucidate the underlying mechanisms.

Effectiveness of early enteral feeding on health outcomes in preterm infants: an overview of systematic reviews.

Early enteral feeding is vital for the physical health of preterm infants. However, there is uncertainty regarding the effects of early enteral feeding on health outcomes in preterm infants. Hence, we aimed to synthesise evidence from systematic reviews (SRs) to evaluate the effects of early enteral feeding on health outcomes in preterm infants. We conducted a literature search in PubMed, Web of Science, Scopus, and the Cochrane Database of Systematic Reviews. SRs selection followed clear inclusion and exclusion criteria. Two reviewers reached a consensus for the inclusion of SRs. The certainty of evidence and the quality of reviews using the GRADE and AMSTAR tools, respectively. We included nine SRs in this review. The effectiveness of early enteral feeding on health outcomes in preterm infants is mainly divided into six primary outcomes: increase the weight gain, reduce the incidence of feed intolerance, shorten the duration of full enteral feeding, reduce the length of hospital stay, reduce the incidence of necrotizing enterocolitis, and decrease the mortality risk. The overall quality of the included SRs was high, whereas most of the evidence was of low or very low certainty. Our results show the impact of early enteral feeding on health outcomes in preterm infants. Although the currently available data indicate that early enteral feeding may improve the health outcomes of preterm infants, additional clinical observation and investigation are required to evaluate the long-term health outcomes of preterm infants who receive early enteral feeding.

The Association of Human Milk Proportion with the Clinical Outcomes of Necrotizing Enterocolitis in Preterm Infants: A Retrospective Study.

Human milk (HM) has been associated with a lower risk of necrotizing enterocolitis (NEC). However, the association of precise HM proportion with the outcome of NEC remains unclear. A total of 77 cases and 154 matched controls were included in this study. The samples were divided into three groups based on the HM proportion of the total enteral intake before NEC onset: ≥70% (HHM), <70% (LHM), and 0% (NHM). The study cohort did not show a significant association between different HM proportions and NEC risk. The adjusted odds ratio (OR) for the highest versus the lowest intake was 0.599. In the prognosis of NEC, different HM proportions significantly affected weight gain, the timing of NEC onset, diagnosis time, hospitalization cost, and the severity of NEC (p < 0.05). Our findings support the beneficial effects of HM on reducing NEC in preterm infants, particularly when a greater proportion of HM of the total enteral intake is included in their feeding. Additionally, the study indicates that preterm infants fed with lower proportions of HM of the total enteral feeding are more prone to experiencing severe cases of NEC.

The Association of Different Proportions of Human Milk of the Total Enteral Intake on Health Outcomes in Preterm Infants: A Systematic Review.

Background: Human milk (HM) is a proven optimal food for preterm infants. However, there is uncertainty regarding the effects of different proportions of HM of the total enteral intake on health outcomes in preterm infants. Therefore, we conducted a systematic review of studies examining the effects of different proportions of HM of the total enteral intake on health outcomes in preterm infants. Methods: We conducted a literature search in the Web of Science, PubMed, and Scopus databases. The methodological quality of the included articles and the certainty of evidence were assessed according to the Newcastle-Ottawa Scale and the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) tool, respectively. Results: Twelve studies were included in the review. Among the clinical findings, the effect of different proportions of HM of the total enteral feeding on health outcomes in preterm infants was divided into six primary outcomes: physical growth, length of stay, morbidity of any disease, all-cause mortality, feeding-related outcomes, and other health outcomes. The studies presented a high risk of bias for most of the domains. The certainty of the evidence was considered low or very low. Conclusions: The findings reiterated that greater proportions of HM positively affect the health outcomes of preterm infants. Overall, when the HM accounts for at least 20% of the total enteral intake, it has an effect on health outcomes in preterm infants. If the proportion of HM reaches 50%, the incidence and severity of necrotizing enterocolitis, as well as the time to reach enteral feeds, will be reduced. Increasing the proportion of HM in enteral feeding should be considered a priority in the feeding strategy for preterm infants in clinical practice.