bluuebunny/crossref_metadata_2025_split huggingface dataset:
Overexpression of IGF2 affects mouse weight and glycolipid metabolism and IGF2 is positively related to macrosomia
Authors: Zhang Qidi , Qin Shengtang , Huai Jing , Yang Huixia , Wei Yumei 
Published: April 2023

ObjectiveTo investigate the effects of insulin-like growth factor 2 (IGF2) on growth and glycolipid metabolism, as well as the underlying mechanism.MethodsA mouse model of IGF2 overexpression was constructed to measure weight gain before adulthood, to obtain the values of adult glycolipid metabolism indicators in the peripheral blood and to detect the expression of genes in the IGF2 signaling pathway in different mouse tissues. The present study also explored the independent association between the IGF2 gene and macrosomia by detecting and comparing the expression levels of IGF2 mRNA/H19 RNA in maternal peripheral blood and fetal cord blood of 26 human pregnancies.ResultsIn the mouse model, weights of the IGF2-overexpressing mice were significantly higher than those of the control mice at the age of 5-10 weeks. The glucose concentration, total cholesterol and high-density lipoprotein cholesterol (HDL-C) levels of IGF2-overexpressing mice were significantly lower than those of wild-type (WT) mice. Compared with the WT mice, the expression of H19 was significantly decreased in the pancreas and IGF1R was significantly decreased in the muscle of mice with IGF2 overexpression. The expression levels of STAT3 and AKT2 showed significant decrease in liver, muscle and increase in muscle of IGF2-overexpressing mice, respectively. GLUT2 expression showed significant increase in liver, kidney, muscle and decrease in pancreas of mice with IGF2 overexpression. This study also found that in normal mothers with the similar clinical characteristics, IGF2 expression in the maternal peripheral blood and fetal cord blood is an independent factor influencing macrosomia. ConclusionIGF2 expression was independently correlated with the occurrence of macrosomia, and overexpression of IGF2 significantly increased the weights of mice at the age of 5-10 weeks and significantly affected the values of adult glycolipid metabolism indicators, which might be the result of changes in the IGF2-IGF1R-STAT3/AKT2-GLUT2/GLUT4 pathway. These findings might suggest that IGF2 plays an important role in growth and glycolipid metabolism during both pregnancy and postnatal development.
Influence of duration of preoperative treatment with phenoxybenzamine and secretory phenotypes on perioperative hemodynamics and postoperative outcomes in pheochromocytoma and paraganglioma
Authors: Yao Yao , Guo Ying , Fan Jing , Lin Tianxin , Wang Lin , Zhang Shaoling 
Published: April 2023

ObjectivesResection of pheochromocytoma and paraganglioma (PPGL) carries risks with perioperative hemodynamic instability. Phenoxybenzamine (PXB) is a commonly used α-blockade to prevent it. It is unclear whether lengthening the preoperative duration of PXB is better for hemodynamic stability and postoperative outcomes. Furthermore, different types of catecholamines have varying effects on perioperative hemodynamics. Thus, our study aimed to investigate the impact of the duration of preoperative preparation with PXB and secretory phenotypes of the patients on intraoperative hemodynamic stability and postoperative complications in PPGL.MethodsBetween Dec 2014 and Jan 2022, 166 patients with PPGL were operated on by the same team at Sun Yat-sen Memorial Hospital. They were divided into group A(1-14d), Group B(15-21d), and Group C(&gt;21d) based on the duration of management with PXB and into the adrenergic and the noradrenergic phenotype group based on secretory profiles. Data on intraoperative hemodynamics and postoperative outcomes were collected and compared among groups.ResultsA total of 96 patients occurred intraoperative hemodynamic instability, and 24 patients had 29 postoperative complications related to the surgery. Among the 145 patients treated with PXB, no significant differences were found in the cumulative time outside the target blood pressure(6.67%[0-17.16%] vs. 5.97%[0-23.08%] vs. 1.22%[0-17.27%], p=0.736) or in the median total HI-score(42.00[30.00-91.00] vs. 89.00[30.00-113.00] vs. 49.00[30.00-93.00], p=0.150) among group A(n=45), B(n=51) and C(n=49). Multivariate analysis demonstrated that the level of plasma-free metanephrine(MN) was an independent risk factor for intraoperative hemodynamic instability. And the median cumulative time outside of the target blood pressure in the adrenergic phenotype group was significantly greater than that in the noradrenergic phenotype group(8.17%[0-26.22%] vs. 1.86%[0-11.74%], p=0.029). However, the median total HI-score(99.50[85.00-113.25] vs. 90.00[78.00-105.00], p=0.570) and postoperative outcomes showed no differences between the two groups.ConclusionsA preoperative duration of nearly 14 days with PXB is sufficient for ensuring intraoperative hemodynamic stability in PPGL. And lengthening the preparation duration may not provide additional benefits in the era of widespread application and advanced techniques of laparoscopic surgery. Additionally, patients with the adrenergic phenotype are more prone to intraoperative hemodynamic instability than the noradrenergic phenotype. Thus, more attention should be given to the adrenergic phenotype during surgery.
Effect of BMI on the value of serum progesterone to predict clinical pregnancy outcome in IVF/ICSI cycles: a retrospective cohort study
Authors: Shen Zhaoyang , Luo Xiaoyan , Xu Jianming , Jiang Yuqing , Chen Wenhui , Yang Qingling , Sun Yingpu 
Published: April 2023

BackgroundNumerous research have investigated the predictor role of progesterone (P) level on the human Chorionic Gonadotropin (hCG) trigger day of assisted reproductive technology (ART) outcomes. However, the relationship of progesterone levels on hCG day to clinical pregnancy outcomes in IVF/ICSI cycles for patients with different BMI groups is still elusive. This study aimed to investigate the effects of progesterone elevation on triggering day on clinical pregnancy rate (CPR) of IVF/ICSI cycles in patients with different female BMI.MethodsWe conducted a retrospective cohort study included 6982 normal-weight parents (18.5Kg/m2≤BMI&lt;25Kg/m2) and 2628 overweight/obese patients (BMI≥25Kg/m2) who underwent fresh day 3 cleavage embryo transfer (ET) in IVF/ICSI cycles utilizing GnRH agonist to control ovarian stimulation.ResultsThe interaction between BMI and P level on triggering day on CPRs was significant (p&lt;0.001). The average level of serum P was reduced with the increase in maternal BMI. Serum P adversely affected CPR in distinct BMI groups. In the normal weight group, CPRs were decreasedas serum P concentrations gradually increased (p&lt;0.001 for overall trend). The CPRs (lower than 65.8%) of progesterone level &gt; 1.00 ng/ml on triggering day were significantly lower than that (72.4%) of progesterone level &lt;0.5 ng/ml. In the overweight/obese group, CPRs showed a decrease statistically with progesterone levels of ≥2.00 ng/ml compared to progesterone levels of &lt;0.5 ng/ml (51.0% VS. 64.9%, p=0.016). After adjusting for confounders, progesterone elevation (PE) negatively correlated with CPRs only in the normal weight group (OR: 0.755 [0.677–0.841], p&lt;0.001), not in the overweight/obese group (p=0.063).ConclusionWomen with higher BMI exhibited a lower progesterone level on triggering day. Additionally, PE on hCG day is related to decreased CPRs in GnRH agonist IVF/ICSI cycles with cleavage embryo transfers regardless of women’s BMI level (normal weight VS. overweight/obesity).
Examining the immunoepigenetic-gut microbiome axis in the context of self-esteem among Native Hawaiians and other Pacific Islanders
Authors: Becerra Celyna Y. , Wells Riley K. , Kunihiro Braden P. , Lee Rosa H. , Umeda Lesley , Allan Nina P. , Rubas Noelle C. , McCracken Trevor A. , Nunokawa Chandler K. L. , Lee Ming-Hao , Pidlaoan Felix Gerard S. , Phankitnirondorn Krit , Dye Christian K. , Yamamoto Brennan Y , Peres Rafael , Juarez Ruben , Maunakea Alika K. 
Published: April 2023

Introduction: Native Hawaiian and other Pacific Islander (NHPI) populations experience higher rates of immunometabolic diseases compared to other racial-ethnic groups in Hawaii. As annual NHPI mortality rates for suicide and type 2 diabetes mellitus (T2DM) exceed those of the state as a whole, understanding the social and biological mechanisms underlying these disparities are urgently needed to enable preventive strategies.Methods: A community-based approach was used to investigate the immunoepigenetic-gut microbiome axis in an NHPI-enriched cohort of Oahu residents (N = 68). Self-esteem (SE) data was collected using a modified Rosenberg self-esteem (SE) assessment as a proxy measure for mental wellbeing in consideration for cultural competency. T2DM status was evaluated using point-of-care A1c (%) tests. Stool samples were collected for 16s-based metagenomic sequencing analyses. Plasma from blood samples were isolated by density-gradient centrifugation. Peripheral blood mononuclear cells (PBMCs) were collected from the same samples and enriched for monocytes using negative selection techniques. Flow-cytometry was used for immunoprofiling assays. Monocyte DNA was extracted for Illumina EPIC array-based methylation analysis.Results: Compared to individuals with normal SE (NSE), those with low SE (LSE) exhibited significantly higher plasma concentrations (pg/ml) of proinflammatory cytokines IL-8 (p = 0.051) and TNF-α (p = 0.011). Metagenomic analysis revealed that the relative abundance (%) of specific gut bacteria significantly differed between SE groups - some of which directly correlated with SE scores. Gene ontology analysis revealed that 104 significantly differentially methylated loci (DML) between SE groups were preferentially located at genes involved in immunometabolic processes. Horvath clock analyses indicated epigenetic age (Epi-Age) deceleration in individuals with LSE and acceleration in individuals with NSE (p = 0.042), yet was not reproduced by other clocks.Discussion: These data reveal novel differences in the immunoepigenetic-gut microbiome axis with respect to SE, warranting further investigation into its relationship to brain activity and mental health in NHPI. Unexpected results from Epi-Age analyses warrant further investigation into the relationship between biological age and disparate health outcomes among the NHPI population. The modifiable component of epigenetic processes and the gut microbiome makes this axis an attractive target for potential therapeutics, biomarker discovery, and novel prevention strategies.
NALCN is a potential biomarker and therapeutic target in human cancers
Authors: He Jian , Xu Jie , Chang Zhiwei , Yan Jiaqin , Zhang Limin , Qin Yanru 
Published: April 2023

Background: Sodium leak channel non-selective (NALCN), known as a voltage-independent Na+ channel, is increasingly considered to play vital roles in tumorigenesis and metastasis of human cancers. However, no comprehensive pan-cancer analysis of NALCN has been conducted. Our study aims to explore the potential diagnostic, prognostic and therapeutic value of NALCN in human cancers.Methods: Through comprehensive application of datasets from Human Protein Atlas (HPA), The Cancer Genome Atlas (TCGA), Cancer Cell Line Encyclopedia (CCLE), Enhanced Version of Tumor Immune Estimation Resource (TIMER2.0), Tumor and Immune System Interaction Database (TISIDB), The University of Alabama at Birmingham Cancer data analysis Portal (UALCAN), cBioPortal, GeneMANIA and Search Tool for the Retrieval of Interaction Gene/Proteins (STRING) databases, we explored the potential roles of NALCN in different cancers. The differential expression, prognostic implications, pathological stages and grades, molecular and immune subtypes, diagnostic accuracy, tumor mutation burden (TMB), microsatellite instability (MSI), mismatch repair (MMR) genes, immune checkpoint genes, chemokine genes, major histocompatibility complex (MHC)-related genes, tumor-infiltrating immune cells (TIICs), promoter methylation, mutations, copy number alteration (CNA), and functional enrichment related to NALCN were analyzed.Results: Most cancers lowly expressed NALCN. Upregulated NALCN expression was associated with poor or better prognosis in different cancers. Moreover, NALCN was correlated with clinicopathological features in multiple cancers. NALCN showed high diagnostic accuracy in 5 caner types. NALCN is highly linked with immune-related biomarkers, immune-related genes and TIICs. Significant methylation changes and genetic alteration of NALCN can be observed in many cancers. Enrichment analysis showed that NALCN is closely related to multiple tumor-related signaling pathways.Conclusion: Our study revealed the vital involvement of NALCN in cancer. NALCN can be used as a prognostic biomarker for immune infiltration and clinical outcomes, and has potential diagnostic and therapeutic implications.
Identification and characterization of a new variation in DPM2 gene in two Chinese siblings with mild intellectual impairment
Authors: Zhao Peiwei , Hu Yanqiu , Hu Juan , Li Cheng , Huang Yufeng , Zhang Lei , Luo Sukun , Zhu Hongmin , Jiang Jun , He Xuelian 
Published: April 2023

Introduction: Congenital disorders of glycosylation (CDGs) are a genetically heterogeneous group of metabolic disorders caused by abnormal protein or lpid glycosylation. DPM2 is one subunit of a heterotrimeric complex for dolichol-phosphatemannose synthase (DPMS), a key enzyme in glycosylation, and only four patients with DPM2-CDG have been reported.Methods: Whole-exome sequencing (WES) was performed in a Chinese family having two siblings with a mild form of DPM2-CDG with developmental delay, mild intellectual disability, hypotonia, and increased serum creatine kinase. Sanger sequencing was used to validate the variants identified in the siblings and their parents. In vitro functional study was performed.Results: A homozygous mutation, c.197G&gt;A (p.Gly66Glu) in exon 4 of DPM2 (NM_003863) was identified by whole exome sequencing (WES). In vitro functional analysis demonstrated that this variant increased the expression level of DPM2 protein and western blot revealed a significant decrease in ICAM1, a universal biomarker for hypoglycosylation in patients with CDG, suggesting abnormal N-linked glycosylation. We also reviewed the 4 previously reported patients carrying homozygous or compound heterozygous variants of DMP2 gene, and found that patients with variants within the region encoding the first domain had more severe clinical symptoms than those with variants within the second domain. However, the actual genotype-phenotype relationship needs more study.Discussion: Overall, our study broadens the variant spectrum of DPM2 gene, attempts to explain the different phenotypes in patients with different DPM2 variants, and emphasizes the need of further functional studies to understand the underlying pathophysiology of the phenotypic heterogeneity.
Classification related to immunogenic cell death predicts prognosis, immune microenvironment characteristics, and response to immunotherapy in lower-grade gliomas
Authors: Kuang Yirui , Jiang Bincan , Zhu Hecheng , Zhou Yi , Huang Haoxuan , Li Can , Zhang Wenlong , Li Xuewen , Cao Yudong 
Published: April 2023

BackgroundImmunogenic cell death (ICD) is a form of cell death that elicits immune responses against the antigens found in dead or dying tumor cells. Growing evidence implies that ICD plays a significant role in triggering antitumor immunity. The prognosis for glioma remains poor despite many biomarkers being reported, and identifying ICD-related biomarkers is imminent for better-personalized management in patients with lower-grade glioma (LGG).Materials and methodsWe identified ICD-related differentially expressed genes (DEGs) by comparing gene expression profiles obtained across Genotype-Tissue Expression (GTEx) and The Cancer Genome Atlas (TCGA) cohorts. On the foundation of ICD-related DEGs, two ICD-related clusters were identified through consensus clustering. Then, survival analysis, functional enrichment analysis, somatic mutation analysis, and immune characteristics analysis were performed in the two ICD-related subtypes. Additionally, we developed and validated a risk assessment signature for LGG patients. Finally, we selected one gene (EIF2AK3) from the above risk model for experimental validation.Results32 ICD-related DEGs were screened, dividing the LGG samples from the TCGA database into two distinct subtypes. The ICD-high subgroup showed worse overall survival (OS), greater immune infiltration, more active immune response process, and higher expression levels of HLA genes than the ICD-low subgroup. Additionally, nine ICD-related DEGs were identified to build the prognostic signature, which was highly correlated with the tumor-immune microenvironment and could unambiguously be taken as an independent prognostic factor and further verified in an external dataset. The experimental results indicated that EIF2AK3 expression was higher in tumors than paracancerous tissues, and high-expression EIF2AK3 was enriched in WHO III and IV gliomas by qPCR and IHC, and Knockdown of EIF2AK3 suppressed cell viability and mobility in glioma cells.ConclusionWe established novel ICD-related subtypes and risk signature for LGG, which may be beneficial to improving clinical outcome prediction and guiding individualized immunotherapy.
A combination of pre-infusion serum ferritin, CRP and IL-6 predicts outcome in relapsed/refractory multiple myeloma patients treated with CAR-T cells
Authors: Liu Yang , Jie Xingxing , Nian Li , Wang Ying , Wang Congyue , Ma Jin , Jiang Jingjing , Wu Qingyun , Qiao Jianlin , Chen Wei , Cao Jiang , Yan Zhiling , Shi Ming , Cheng Hai , Zhu Feng , Sang Wei , Li Depeng , Chen Chong , Xu Kailin , Li Zhenyu 
Published: April 2023

BackgroundChimeric antigen receptor - T (CAR-T) cell therapy has shown remarkable efficacy in patients with relapsed/refractory multiple myeloma (R/R MM). However, a subset of patients still experienced progression or relapse, and the predictors of prognosis are little known. We analyzed the inflammatory markers before CAR-T cell infusion, to clarify their correlation with survival and toxicity.MethodsThis study involved 109 R/R MM patients who received CAR-T therapy between June 2017 and July 2021. Inflammatory markers, including ferritin, c-reactive protein (CRP), and interleukin-6 (IL-6) before CAR-T cell infusion were detected and then categorized by quartiles. Adverse events and clinical outcomes were compared between patients with upper quartile of inflammatory markers and patients with lower three quartiles of inflammatory markers. An inflammatory prognostic index (InPI) based on these three inflammatory markers was developed in this study. Patients were divided into 3 groups according to the InPI score, progression-free survival (PFS) and overall survival (OS) were compared among the groups. In addition, we explored the correlation between cytokine release syndrome (CRS) and pre-infusion inflammatory markers.ResultsWe found that the pre-infusion high ferritin (hazard ratio [HR], 3.382; 95% confidence interval [CI], 1.667 to 6.863; P = .0007), high CRP (HR, 2.043; 95% CI, 1.019 to 4.097; P = .044), and high IL-6 (HR, 3.298; 95% CI, 1.598 to 6.808; P = .0013) were significantly associated with inferior OS. The formula of the InPI score was based on the HR value of these 3 variables. Three risk groups were formed: (good, 0 to 0.5 point; intermediate, 1 to 1.5 points; poor, 2 to 2.5 points). Median OS for patients with good, intermediate, and poor InPI was not reached, 24 months, and 4 months, respectively, and median PFS was 19.1 months, 12.3 months, and 2.9 months, respectively. In the cox proportional hazards model, poor InPI remained an independent prognostic factor for PFS and OS. Pre-infusion ferritin was negatively associated with CAR T-cell expansion normalized to baseline tumor burden. Spearman correlation analysis showed that pre-infusion ferritin and IL-6 levels positively correlated with the grade of CRS (P = .0369 and P = .0117, respectively). The incidence of severe CRS was higher in patients with high IL-6 compared with patients with low IL-6 (26% vs. 9%, P = .0405). Pre-infusion ferritin, CRP and IL-6 were positively correlated with each peak values within the first month after infusion.ConclusionsOur results suggest that patients with elevated inflammation markers before CAR-T cell infusion are more likely to have poor prognosis.
A relay of anticyclonic eddies transferring North Pacific subtropical mode water into the South China Sea
Authors: Wang Ran , Ren Qiang , Nan Feng , Yu Fei 
Published: April 2023

North Pacific subtropical mode waters (STMWs), which are subducted with air-sea interaction signals and characterized by low potential vorticity (PV), play an important role in climate change issues. STMW (PV<2×10−10 m−1· s−1) can be advected westward by large-scale ocean circulation and mesoscale eddies. However, whether and how the STMW intrudes into the South China Sea (SCS) remains unclear. Low PV signals that originate from the STMW and intruding into the SCS are investigated by comparing observations and ocean general circulation models during 2003-2017. These signals mostly move across the Luzon Strait (LS) into the SCS during the 2008-2009 and 2014-2016 periods. The results of case studies selected from these two periods indicate that the low PV signals can move to the LS and are trapped by anticyclonic eddies (AEs). When the velocity vorticity is negative southwest of Taiwan Island, vertical stratification becomes weaker west of the coming AE (AE1), and low PV signals can consequently be transported along the STMW layer (25.0 σθ- 25.5 σθ isopycnal layer). Thus, an AE (AE2) forms east of AE1 and isolates the low PV signal from AE1, and then AE2 transports the low PV water southwestward in the SCS. In contrast, the low PV signal has difficulty migrating eastward when the velocity vorticity is positive west of AE1, as vertical stratification strengthens and then weakens that signal. The results suggest that only AEs can relay low PV signals from east of the LS and carry them over long distances in the SCS.