Analysis of the risk factors in patients with unexplained recurrent spontaneous abortion.

PROBLEM: We aimed to explore the risk factors in patients with unexplained recurrent spontaneous abortion (URSA) and to provide a basis for clinically targeted therapy. METHOD OF STUDY: This case-control study comprised 202 patients with URSA treated at our hospital and 115 women in early pregnancy with a normal birth history during the same period. After procuring the data we conducted a multivariate logistic regression analysis of risk factors related to URSA. RESULTS: Logistic regression analysis showed (i) that the number of spontaneous abortions (SAs; odds ratio [OR] = 492.123), the levels of autoantibodies (OR = 19.322) and tumor necrosis factor alpha (TNF-α; OR = 9.615), and the CT and TT genotypes of methylenetetrahydrofolate reductase (MTHFR) C677T (OR = 6.217 and 15.009, respectively) were risk factors for URSA and (ii) that 25-hydroxyvitamin D (25-(OH)D; OR = 0.919) was a protective factor. The most important risk factor was a history of one or more SAs, with the risk of pregnancy loss increasing 491.123-fold. Every unit increase in serum 25-(OH)D reduced the risk of SA by 8.1%. CONCLUSIONS: The risk factors for URSA included the number of SAs, the levels of autoantibodies and TNF-α, and the MTHFR C677T T allele; 25-(OH)D was a protective factor. We recommend that women diagnosed with URSA receive intervention as soon as possible so as to actively reduce the incidence of recurrent SA.

Correlation between tumor markers and type 2 diabetes mellitus complications and their related influencing factors.

BACKGROUND: This study aims to investigate the correlation between type 2 diabetes mellitus (T2DM) and the tumor markers/biochemical parameters of patients, as well as the related factors leading to complications. METHODS: A total of 150 T2DM patients in our hospital were included as the research group, and 80 healthy persons were matched in the normal control group. The levels of tumor markers (CA199, CEA, CA153, CA125, AFP) and body mass index (BMI), waist-to-hip ratio (WHR), blood pressure (BP), fasting plasma glucose (FPG), glycosylated hemoglobin (HbA1c), urine microalbumin (M-ALB), and triglyceride (TG) in the two groups were determined. Based on the complications status of T2DM patients, the patients were further divided into a complication-free group (patients with simple diabetes) and complication group. Univariate analysis was performed between patients with and without complications. RESULTS: The levels of serum CA199, CEA, and CA125 in the study group were significantly higher than those in the normal control group (all P<0.0001), and the levels of BMI, WHR, systolic BP (SBP), diastolic BP (DBP), FPG, HbA1c, M-ALB, and TG in the study group were significantly higher than those in the control group (all P<0.05). Tumor markers CA199, CEA, and CA125 were positively correlated with BMI, WHR, BP, FPG, HbA1c, M-ALB, and TG. Smoking, family history of diabetes, combined hypertension, hyperlipemia, course of disease, CA199, CEA, CA153, CA125, AFP, SBP, DBP, FPG, HbA1c, M-ALB, and TG were the influencing factors of complications in T2DM patients. CONCLUSIONS: Relevant indicators of T2DM patients with complications should be fully evaluated clinically, and long-term follow-up observation should be conducted, so as to reduce the occurrence of complications.

Scutellarin alleviates type 2 diabetes (HFD/low dose STZ)-induced cardiac injury through modulation of oxidative stress, inflammation, apoptosis and fibrosis in mice.

BACKGROUND: Diabetes is a serious global health concern which severely affected public health as well as socio-economic growth worldwide. Scutellarin (SCU), a bioactive flavonoid, is known for its efficacious action against a range of ailments including cardiovascular problems. The present study was conducted to find out possible protective effect and its associated mechanisms of SCU on experimental type 2 diabetes-induced cardiac injury. METHODS: Type 2 diabetes was induced by treating animals with high fat diet for 4 weeks and a single intraperitoneal dose (35 mg/kg body weight) of streptozotocin and diabetic animals received SCU (10 or 20 mg/kg/day) for 6 weeks. RESULTS: Scutellarin attenuated type 2 diabetes-induced hyperglycemia, bodyweight loss, hyperlipidaemia, cardiac functional damage with histopathological alterations and fibrosis. Scutellarin treatment to type 2 diabetic mice ameliorated oxidative stress, inflammatory status and apoptosis in heart. Furthermore, the underlying mechanisms for such mitigation of oxidative stress, inflammation and apoptosis in heart involved modulation of Nrf2/Keap1 pathway, TLR4/MyD88/NF-κB mediated inflammatory pathway and intrinsic (mitochondrial) apoptosis pathway, respectively. CONCLUSIONS: The current findings suggest that SCU is effective in protecting type 2 diabetes-induced cardiac injury by attenuating oxidative stress and inflammatory responses and apoptosis, and it is also worth considering the efficacious potential of SCU to treat diabetic cardiomyopathy patients.

Effects of a diet with or without physical activity on angiopoietin-like protein 8 concentrations in overweight/obese patients with newly diagnosed type 2 diabetes: a randomized controlled trial.

Angiopoietin-like protein 8 (ANGPTL8) is a newly discovered adipokine plays an important role in energy homoeostasis, obesity and type 2 diabetes (T2D). Although lifestyle modification in obesity and T2D is known to offer metabolic benefits, there is paucity of comprehensive data on change in ANGPTL8. We investigated the effect of lifestyle intervention on ANGPTL8 concentrations. 384 obese/overweight adults with newly diagnosed T2D were randomly assigned (1:1:1) to diet (n = 128), diet + activity (n = 128) or usual care (control, n = 128) groups. All patients received usual care. Besides, the diet group received a calorie-restricted diet aiming for a weight loss of 5-10%. The diet + activity group additionally received a pedometer-based walking program. Primary outcome was change in ANGPTL8 concentration at 6 months. Data were analyzed according to intention-to-treat. From baseline to 6 months, the median ANGPTL8 level changed from 804.38 pg/mL to 792.86 pg/mL in control group. Compared with control, ANGPTL8 decreased with diet (baseline-adjusted between-group difference was -121.00 pg/mL, 95% CI -177.47 to -64.53; p < 0.0001) and diet + activity (-126.16 pg/mL, -181.21 to -71.11; p < 0.0001). There was no greater effect of diet + activity compared with diet (-5.16 pg/mL, -53.63 to 43.31; p = 0.8348). Both effects disappeared after adjusting for change in body fat, but did not differ significantly when adjusting for physical activity. A 6-month intervention inducing weight loss by a calorie-restricted diet or diet + activity, resulted in significant decrease on ANGPTL8 concentration. These effects were established by change in total body fat, and not by change in physical activity.

Elevated E2F7 expression predicts poor prognosis in human patients with gliomas.

E2F transcription factors have been studied extensively in a broad range of organisms as major regulators of cell cycle, apoptosis, and differentiation. The E2F family includes the atypical member E2F7, which has been rarely studied in gliomas. The aim of this study is to determine the expression status of E2F7 in gliomas, its relationship to clinicopathological features, and patients' outcome. The mRNA levels of E2F7 in the human brain and different grades of gliomas were analysed using datasets from the publically available Oncomine database. One of the most significant co-expression factors, CDK1, together with E2F7, was further validated by immunohistochemistry in 90 different grades of gliomas. Furthermore, univariate and multivariate analyses were performed to identify prognostic variables relative to patient and tumour characteristics and treatment modalities. E2F7 mRNA expression was found to be elevated in gliomas by Oncomine-database analysis. Immunohistochemistry showed an increase in E2F7 labelling index in high- versus low-grade gliomas (62.1±11.8% vs. 18.9±10.2%, p<0.0001). There was a positive correlation between E2F7 and CDK1 immunoreactivity (Spearman r=0.446, p=0.037). Clinicopathological evaluation suggested that E2F7 expression was associated with tumour grade (p<0.0001) and recurrence (p=0.025). In Cox multivariate analysis, pathological classification and recurrence were independent prognostic factors of gliomas, and E2F7 was significantly related to progression-free survival (p=0.011), but not overall survival (p=0.062). Our findings suggested that E2F7 might act as an independent prognostic factor of gliomas and might constitute a potential therapeutic target for this disease.

Proton-bound complex mediating retro-Michael-type fragmentation of protonated 3-substituted oxindoles in the Orbitrap high-energy collisional dissociation cell.

RATIONALE: Oxindole derivatives are valuable building blocks for indole chemistry. Systematically exploring the fragmentation behavior of the protonated 3-pyrazole-substituted oxindoles by kinetic methods combined with density functional theory (DFT) calculations is useful for further understanding their basic properties, and might provide some insights into their reactivity trends in synthesis and metabolism. METHODS: All high-resolution high-energy collision-induced dissociation tandem mass spectrometry (CID-MS/MS) experiments were carried out using electrospray ionization hybrid Quadrupole-Orbitrap mass spectrometry in positive ion mode. Theoretical calculations were carried out by the DFT method at the B3LYP level with the 6-311G (d, p) basis set in the Gaussian 03 package of programs. RESULTS: In the fragmentation of protonated 3-pyrazole-substituted oxindoles, the characterized protonated 3-(3-methyl-5-oxo-1H-pyrazol-4(5H)-ylidene)indolin-2-one derivatives and the protonated 5-methylpyrazolone were observed, which were proposed from the cleavage of the C(ß)-C(γ) bond in a retro-Michael reaction. With the kinetic plot, a linear correlation was established between the intensities of this two competitive product ions and the difference in proton affinities of the corresponding neutral molecules, which demonstrated that the retro-Michael reaction was mediated by a proton-bound complex. CONCLUSIONS: Using the kinetic method combined with theoretical calculations, a proton-bound complex mediating retro-Michael reaction was proposed for the fragmentation of protonated 3-pyrazole-substituted oxindoles in the high-energy collisional dissociation tandem mass spectrometry for the first time, which provided potential evidence to further understand their intrinsic bioactivities.

Solid-phase extraction based on chloromethylated polystyrene magnetic nanospheres followed by gas chromatography with mass spectrometry to determine phthalate esters in beverages.

An ultrasound-assisted magnetic solid-phase extraction procedure with chloromethylated polystyrene-coated Fe3 O4 nanospheres as magnetic adsorbents has been developed to determine eight phthalate esters (bis(4-methyl-2-pentyl) phthalate, dipentyl phthalate, dihexyl phthalate, benzyl butyl phthalate, bis(2-butoxyethyl) phthalate, dicyclohexyl phthalate, di-n-octyl phthalate, and dinonyl phthalate) simultaneously in beverage samples, in combination with gas chromatography coupled to tandem mass spectrometry for the first time. Several factors related to magnetic solid-phase extraction efficiencies, such as amount of adsorbent, extracting time, ionic strength, and desorption conditions were investigated. The enrichment factors of the method for the eight analytes were over 2482. A good linearity was observed in the range of 10-500 ng/L for bis(2-butoxyethyl) phthalate and 2-500 ng/L for the other phthalate esters with correlation coefficients ranging from 0.9980 to 0.9998. The limits of detection and quantification for the eight phthalate esters were in the range of 0.20-2.90 and 0.67-9.67 ng/L, respectively. The mean recoveries at three spiked levels were 75.8-117.7%, the coefficients of variations were <11.6%. The proposed method was demonstrated to be a simple and efficient technique for the trace analysis of the phthalate esters in beverage samples.