Association of Maternal Body Mass Index With Risk of Infant Mortality: A Dose-Response Meta-Analysis

Objective: This study presumed that a high or low bodymass index (BMI)might increase the risk of infant mortality. Therefore, a meta-analysis was performed to systematically assess the association between maternal BMI and the risk of infant mortality. Methods: The electronic databases, including Pubmed, Embase database, and Cochrane Library, were systemically searched by two investigators from inception to November 26th, 2020, with no language restriction. In parallel, a dose-response was assessed. Results: Finally, 22 cohort studies involving 13,532,293 participants were included into this paper, which showed that compared with normal BMI, maternal overweight significantly increased the risks of infant mortality [risk ratio (RR), 1.16; 95% confidence interval (CI), 1.13–1.19], neonatal mortality (RR, 1.23; 95% CI, 1.08–1.39), early neonatal mortality (RR, 1.55; 95% CI, 1.26–1.92) and post-neonatal mortality (RR, 1.18; 95% CI, 1.07–1.29). Similarly, maternal obesity significantly increased the risk of infant mortality (RR, 1.55; 95% CI, 1.41–1.70), neonatal mortality (RR, 1.55; 95% CI, 1.28–1.67), early neonatal mortality (RR, 1.37; 95% CI, 1.13–1.67), and post-neonatal mortality (RR, 1.30; 95% CI, 1.03–1.65), whereas maternal underweight potentially decreased the risk of infant mortality (RR, 0.93; 95% CI, 0.88–0.98). In the dose-response analysis, the risk of infant mortality significantly increased when the maternal BMI was >25 kg/m2. Conclusions: Maternal overweight or obesity significantly increases the risks of infant mortality, neonatal mortality, early neonatal mortality, and post-neonatal mortality compared with normal BMI in a dose-dependentmanner. Besides,maternal underweight will not increase the risk of infant mortality, neonatal mortality, early neonatal mortality, or postneonatal mortality; instead, it tends to decrease the risk of infant mortality. Early weight management may provide potential benefits to infants, and more large-scale prospective studies are needed to verify this finding in the future

Association of Maternal Body Mass Index With Risk of Infant Mortality: A Dose-Response Meta-Analysis

Objective: This study presumed that a high or low bodymass index (BMI)might increase the risk of infant mortality. Therefore, a meta-analysis was performed to systematically assess the association between maternal BMI and the risk of infant mortality. Methods: The electronic databases, including Pubmed, Embase database, and Cochrane Library, were systemically searched by two investigators from inception to November 26th, 2020, with no language restriction. In parallel, a dose-response was assessed. Results: Finally, 22 cohort studies involving 13,532,293 participants were included into this paper, which showed that compared with normal BMI, maternal overweight significantly increased the risks of infant mortality [risk ratio (RR), 1.16; 95% confidence interval (CI), 1.13–1.19], neonatal mortality (RR, 1.23; 95% CI, 1.08–1.39), early neonatal mortality (RR, 1.55; 95% CI, 1.26–1.92) and post-neonatal mortality (RR, 1.18; 95% CI, 1.07–1.29). Similarly, maternal obesity significantly increased the risk of infant mortality (RR, 1.55; 95% CI, 1.41–1.70), neonatal mortality (RR, 1.55; 95% CI, 1.28–1.67), early neonatal mortality (RR, 1.37; 95% CI, 1.13–1.67), and post-neonatal mortality (RR, 1.30; 95% CI, 1.03–1.65), whereas maternal underweight potentially decreased the risk of infant mortality (RR, 0.93; 95% CI, 0.88–0.98). In the dose-response analysis, the risk of infant mortality significantly increased when the maternal BMI was >25 kg/m2. Conclusions: Maternal overweight or obesity significantly increases the risks of infant mortality, neonatal mortality, early neonatal mortality, and post-neonatal mortality compared with normal BMI in a dose-dependentmanner. Besides,maternal underweight will not increase the risk of infant mortality, neonatal mortality, early neonatal mortality, or postneonatal mortality; instead, it tends to decrease the risk of infant mortality. Early weight management may provide potential benefits to infants, and more large-scale prospective studies are needed to verify this finding in the future

Association of Maternal Body Mass Index With Risk of Infant Mortality: A Dose-Response Meta-Analysis

Objective: This study presumed that a high or low bodymass index (BMI)might increase the risk of infant mortality. Therefore, a meta-analysis was performed to systematically assess the association between maternal BMI and the risk of infant mortality. Methods: The electronic databases, including Pubmed, Embase database, and Cochrane Library, were systemically searched by two investigators from inception to November 26th, 2020, with no language restriction. In parallel, a dose-response was assessed. Results: Finally, 22 cohort studies involving 13,532,293 participants were included into this paper, which showed that compared with normal BMI, maternal overweight significantly increased the risks of infant mortality [risk ratio (RR), 1.16; 95% confidence interval (CI), 1.13–1.19], neonatal mortality (RR, 1.23; 95% CI, 1.08–1.39), early neonatal mortality (RR, 1.55; 95% CI, 1.26–1.92) and post-neonatal mortality (RR, 1.18; 95% CI, 1.07–1.29). Similarly, maternal obesity significantly increased the risk of infant mortality (RR, 1.55; 95% CI, 1.41–1.70), neonatal mortality (RR, 1.55; 95% CI, 1.28–1.67), early neonatal mortality (RR, 1.37; 95% CI, 1.13–1.67), and post-neonatal mortality (RR, 1.30; 95% CI, 1.03–1.65), whereas maternal underweight potentially decreased the risk of infant mortality (RR, 0.93; 95% CI, 0.88–0.98). In the dose-response analysis, the risk of infant mortality significantly increased when the maternal BMI was >25 kg/m2. Conclusions: Maternal overweight or obesity significantly increases the risks of infant mortality, neonatal mortality, early neonatal mortality, and post-neonatal mortality compared with normal BMI in a dose-dependentmanner. Besides,maternal underweight will not increase the risk of infant mortality, neonatal mortality, early neonatal mortality, or postneonatal mortality; instead, it tends to decrease the risk of infant mortality. Early weight management may provide potential benefits to infants, and more large-scale prospective studies are needed to verify this finding in the future

Synergistic Antitumor Effects of Anlotinib Combined with Oral 5-Fluorouracil/S-1 via Inhibiting Src/AKT Signaling Pathway in Small-Cell Lung Cancer

Background. Small-molecule tyrosine inhibitor anlotinib which developed in China has been approved as a third-line treatment for patients with small-cell lung cancer (SCLC). Our previous clinical study found that anlotinib combined with S-1 has better short-term ORR than the single-agent anlotinib of SCLC and other small-molecule vascular targeted drug therapies in the treatment of SCLC. However, the molecular mechanism of those effect remains unclear. Methods. SCLC cell line H446 was treated with either anlotinib, 5-FU alone, or combination. The cellular effects including cell viability, cell apoptosis, cell cycle, cell migration, and invasion were explored to evaluate the cell proliferation level. Western blot was performed to determine the protein levels of the combined action of the two drugs. The xenograft mouse model was established by injection of H446 cells into mouse, and the animals were randomized and assigned for the drug treatments. Body weights and tumor sizes were recorded. WB was conducted using tumor tissues. All data were collected and statistically analyzed using t-test to reveal the underlying molecular mechanism. Results. When anlotinib was combined with 5-FU, the IC50 value of cells was significantly reduced. And apoptosis, cell cycle arrest, and cell motility rates were stronger when anlotinib combined with 5-FU than in the anlotinib or 5-FU alone. In H446 cell-derived xenograft mouse model, tumor volumes were significantly decreased in Anlo/5-FU combination group than anlotinib or 5-FU alone group. Western blot showed the decreasing expression of p-Src/p-AKT in the Anlo/5-FU group. Conclusion. Our data revealed that the treatment of combination of antitumor angiogenesis agent anlotinib with chemotherapy drug 5-FU may have synergistic cytotoxicity to SCLC in vitro and in vivo. This treatment modality reduced cell proliferation and migration via Src/AKT pathway. This new strategy may be a promising treatment for SCLC but needs to be confirmed in future clinical trials

Altered Resting-State Functional Networks in Nondialysis Patients with Stage 5 Chronic Kidney Disease: A Graph–Theoretical Analysis

This study aimed to investigate the topological characteristics of the resting-state functional network and the underlying pathological mechanism in nondialysis patients with stage 5 chronic kidney disease (CKD5 ND). Eighty-five subjects (21 patients with CKD5 ND, 32 patients with CKD on maintenance hemodialysis (HD), and 32 healthy controls (HCs)) underwent laboratory examinations, neuropsychological tests, and brain magnetic resonance imaging. The topological characteristics of networks were compared with a graph–theoretical approach, and correlations between neuropsychological scores and network properties were analyzed. All participants exhibited networks with small-world attributes, and global topological attributes were impaired in both groups of patients with CKD 5 (ND and HD) compared with HCs (p p p p p p = 0.01) was positively correlated with MoCA scores. In conclusion, all CKD5 ND patients exhibited changes in functional network topological properties and were closely associated with mild cognitive impairment. More interestingly, the topological property changes in CKD5 ND patients were dominated by basal ganglia areas, which may be more helpful to understand and possibly reveal the underlying pathological mechanisms of cognitive impairment in CKD5 ND

Discovery and characterization of functional modules and pathogenic genes associated with the risk of coronary artery disease

An integrated network biology approach for identifying disease risk functional modules and risk pathogenic genes for associated with CAD risk.</p

Discovery of a New Series of Naphthamides as Potent VEGFR‑2 Kinase Inhibitors

Inhibition of VEGFR-2 signaling pathway has already become one of the most promising approaches for the treatment of cancer. In this study, we describe the design, synthesis, and biological evaluation of a new series of naphthamides as potent inhibitors of VEGFR-2. Among these compounds, <b>14c</b> exhibited high VEGFR-2 inhibitory potency in both enzymatic and HUVEC cellular proliferation assays, with IC₅₀ values of 1.5 and 0.9 nM, respectively. Kinase selectivity profiling revealed that <b>14c</b> was a multitargeted inhibitor, and it also exhibited good potency against VEGFR-1, PDGFR-β, and RET. Furthermore, <b>14c</b> effectively blocked tube formation of HUVEC at nanomolar level. Overall, <b>14c</b> might be a promising candidate for the treatment of cancer

Preclinical and early clinical studies of a novel compound SYHA1813 that efficiently crosses the blood–brain barrier and exhibits potent activity against glioblastoma

Glioblastoma (GBM) is the most common and aggressive malignant brain tumor in adults and is poorly controlled. Previous studies have shown that both macrophages and angiogenesis play significant roles in GBM progression, and co-targeting of CSF1R and VEGFR is likely to be an effective strategy for GBM treatment. Therefore, this study developed a novel and selective inhibitor of CSF1R and VEGFR, SYHA1813, possessing potent antitumor activity against GBM. SYHA1813 inhibited VEGFR and CSF1R kinase activities with high potency and selectivity and thus blocked the cell viability of HUVECs and macrophages and exhibited anti-angiogenetic effects both in vitro and in vivo. SYHA1813 also displayed potent in vivo antitumor activity against GBM in immune-competent and immune-deficient mouse models, including temozolomide (TMZ) insensitive tumors. Notably, SYHA1813 could penetrate the blood–brain barrier (BBB) and prolong the survival time of mice bearing intracranial GBM xenografts. Moreover, SYHA1813 treatment resulted in a synergistic antitumor efficacy in combination with the PD-1 antibody. As a clinical proof of concept, SYHA1813 achieved confirmed responses in patients with recurrent GBM in an ongoing first-in-human phase I trial. The data of this study support the rationale for an ongoing phase I clinical study (ChiCTR2100045380)