The association between plasma free amino acids and type 2 diabetes mellitus complicated with infection in Chinese patients.

BACKGROUND: Type 2 diabetes mellitus (T2DM), one of the most common public diseases threatening human health, is always accompanied by infection. Though there are still a variety of flaws in the treatment of some infectious diseases, metabolomics provides a fresh perspective to explore the relationship between T2DM and infection. Our research aimed to investigate the association between plasma free amino acids (PFAAs) and T2DM complicated with infection in Chinese patients. METHODS: A cross-sectional study was conducted from May 2015 to August 2016. We retrieved the medical records of 1032 inpatients with T2DM from Liaoning Medical University First Affiliated Hospital and we used mass spectrometry to quantify 23 PFAAs. Infections contained 15 individual categories that could be retrieved from the database. Principal component analysis was used to extract factors of PFAAs. Multi-variable binary logistic regression was used to obtain odds ratios (OR) and their 95% confidence intervals (CI). RESULTS: Among 1032 inpatients,109 (10.6%) had infectious diseases. Six factors, accounting for 68.6% of the total variance, were extracted. Factor 4 consisted of Glu, Asp and Orn. Factor 5 consisted of Hcy and Pip. After adjusting for potential confounders, factor 4 was positively correlated with T2DM complicated with infection in Chinese T2DM patients (OR: 1.27, 95%CI: 1.06-1.52). Individual Hcy in factor 5 was positively associated with T2DM complicated with infection (OR: 1.33, 95%CI: 1.08-1.64). Furthermore, factor 4 (OR: 1.44, 95%CI: 1.11-1.87), Orn (OR: 1.01, 95%CI: 1.00-1.02) and Hcy (OR: 1.56, 95%CI: 1.14-3.14) were positively associated with bacterial infection in Chinese T2DM patients, while factor 5 (OR: 0.71, 95%CI: 0.50-1.00) was negatively associated with bacterial infection. CONCLUSIONS: Urea cycle-related metabolites (Orn, Asp, Glu) and Hcy were positively associated with T2DM complicated with infection in China. Orn and Hcy were positively associated with bacterial infection in T2DM patients in China.

Inferring Causal Relationships Between Metabolites and Polycystic Ovary Syndrome Using Summary Statistics from Genome­Wide Association Studies.

Polycystic ovary syndrome (PCOS) is a disorder characterized by hyperandrogenism, ovulatory dysfunction, and polycystic ovarian morphology. Previous studies have suggested that metabolites may play a pivotal mediating role in the progression of phenotypic variations. Although several metabolites had been identified as potential markers for PCOS, the relationship between blood metabolites and PCOS was not comprehensively explored. Previously, Pickrell et al. designed a robust approach to infer evidence of a causal relationship between different phenotypes using independently putative causal SNPs. Our previous paper extended this approach to make it more suitable for cases where only a few independently putative causal SNPs were identified to be significantly associated with the phenotypes (i.e., metabolites). When the most significant SNPs in each independent locus (the independent lead SNPs) with p-values of < 1 × 10-5 were used, 3 metabolites (2-tetradecenoyl carnitine, threitol, 1-docosahexaenoylglycerophosphocholine) causally influencing PCOS and 2 metabolites (asparagine and phenyllactate) influenced by PCOS were identified, (relative likelihood r < 0.01). Under a less stringent threshold of r < 0.05, 7 metabolites (trans-4-hydroxyproline, glutaroyl carnitine, stachydrine, undecanoate, 7-Hoca, N-acetylalanine and 2-hydroxyisobutyrate) were identified. Taken together, this study can provide novel insights into the pathophysiological mechanisms underlying PCOS; whether these metabolites can serve as biomarkers to predict PCOS in clinical practice warrants further investigations.

Relationship between plasma glutamate and cardiovascular disease risk in Chinese patients with type 2 diabetes mellitus by gender.

Objectives: This study aimed to assess the association between plasma glutamate (Glu) and the risk of cardiovascular disease (CVD) in patients with type 2 diabetes mellitus (T2DM) and whether this association differs by gender. Material and methods: We retrieved clinical information on 1032 consecutive patients with T2DM from a same tertiary care center from May 2015 to August 2016. Glu was quantified by liquid chromatography-tandem mass spectrometry analysis. Glu was converted into a categorical variable based on the median concentration in the whole population, while logistic regression was used to obtain the odds ratio (OR) and 95% confidence interval (CI), and the correlation between Glu and various biochemical indices was analyzed. Results: We found that Glu was positively associated with the risk of CVD in patients with T2DM. This correlation was more significant in women. In T2DM patients, the higher the age, body mass index (BMI), weight and systolic blood pressure (SBP), the lower the glycosylated hemoglobin (HbA1C) concentration and the higher the Glu. In female patients, the correlation between age, weight, BMI, SBP, and plasma Triglycerides (TG), and Glu was also statistically significant. Conclusion: In conclusion, female T2DM patients with high levels of Glu have a higher risk of developing CVD.

Highly Sensitive Lanthanide-Doped Nanoparticles-Based Point-of-Care Diagnosis of Human Cardiac Troponin I.

INTRODUCTION: Cardiac troponin I (cTnI) has been regarded as a gold standard for early diagnosis and prognosis monitoring of acute myocardial infarction (AMI) in clinical practice. Owing to its low concentration in blood, accurate determination of cTnI often requires high sensitivity. However, current established point-of-care (POC) assays are insufficient to meet clinically analytical requirements due to their low sensitivity. METHODS: To this end, we established a highly sensitive and reliable POC lateral flow strip based on lanthanide-doped nanoparticles (NPs) for cTnI determination in human blood samples. The capture of cTnI on the lateral flow strip was performed in a sandwich assay, where Eu3+-doped vanadate nanoparticles (GdVO4:30% Eu NPs) were used as luminescent probes to allow quantification. RESULTS: Our platform realized the analytical sensitivity enhancement with limit-of-detection (LOD) as low as 17 pg mL-1 for cTnI detection, which was lower than the commercial counterpart; meanwhile, it displayed high specificity, excellent reproducibility and outstanding accuracy for analyzing clinical serum samples. CONCLUSION: Overall, this strategy provided an ultrasensitive, cost-effective and user-friendly platform for on-site cTnI detection, demonstrating the prospect of lanthanide-doped NPs-based POC diagnosis of disease-related biomarkers.

Notch1/3 and p53/p21 are a potential therapeutic target for APS-induced apoptosis in non-small cell lung carcinoma cell lines.

OBJECTIVE: Previous studies have shown that Astragalus polysaccharide (APS) can be applied to anti-cancer. However, the mechanism by which APS mediate this effect is unclear. In the present study, APS-mediated NSCLC cell apoptosis was investigated through the regulation of the notch signaling pathway. METHODS: The cell viability was detected by the CCK8 assay. The mRNA and protein expression of notch1/3 and tumor suppressors were analyzed by RT-PCR and western blotting, respectively. RESULTS: The mRNA and protein of notch1 and notch3 were significantly up-regulated in tumor tissues as compared to non-tumor adjacent tissues. Treatment of human NSCLC cells with APS induced cell death in a dose-and time-dependent manner by using CCK8 assay. The mRNA and protein expression of notch1 and notch3 were significantly lower in NSCLC cells with APS treatment than that in control group. Moreover, western blotting analysis showed that treatment of H460 cells with APS significantly increased the pro-apoptotic Bax and caspase 8 levels, decreased the anti-apoptotic Bcl-2 level. Furthermore, p53, p21 and p16 were obviously up-regulated by APS treatment in H460 cell. CONCLUSIONS: This study demonstrated that APS-treated could inhibit proliferation and promote cell apoptosis, at least partially, through suppressing the expression of notch1 and notch3 and up-regulating the expression of tumor suppressors in H460 NSCLC cell lines.

Belching, regurgitation, chest tightness and dyspnea: not gastroesophageal reflux disease but asthma.

Belching is a common symptom of gastroesophageal reflux disease. If the symptoms are not relieved after anti-reflux treatment, another etiology should be considered. Here, we report a case of a 43-year-old man who presented with belching, regurgitation, chest tightness and dyspnea for 18 mo, which became gradually more severe. Gastroscopic examination suggested superficial gastritis. Twenty-four-hour esophageal pH monitoring showed that the Demeester score was 11.4, in the normal range. High-resolution manometry showed that integrated relaxation pressure and intrabolus pressure were higher than normal (20 mmHg and 22.4 mmHg, respectively), indicating gastroesophageal junction outflow tract obstruction. Pulmonary function test showed severe obstructive ventilation dysfunction [forced expiratory volume in 1 second (FEV1)/forced vital capacity 32%, FEV1 was 1.21 L, occupying 35% predicted value after salbuterol inhalation], and positive bronchial dilation test (∆FEV1 260 mL, ∆FEV1% 27%). Skin prick test showed Dermatophagoides farinae (++), house dust mite (++++), and shrimp protein (++). Fractional exhaled nitric oxide measurement was 76 ppb. All the symptoms were alleviated completely and pulmonary function increased after combination therapy with corticosteroids and long-acting ß2-agonist. Bronchial asthma was eventually diagnosed by laboratory tests and the effect of anti-asthmatic treatment, therefore, physicians, especially the Gastrointestinal physicians, should pay attention to the belching symptoms of asthma.

[Effects on chemotactic factor expression in bronchial epithelial cells by co-stimulation of poly(I:C) and lipopolysaccharide and the underlying mechanism].

AIM: To investigate the effect of co-stimulation of mimic viral infection [polyinosinic: polycytidylic acid, poly(I:C)] and endotoxin (lipopolysaccharide, LPS) on chemotactic factors production of human bronchial epithelial cells and explore its related mechanism. METHODS: Human bronchial epithelial cells (16HBE) were challenged by co-stimulation of different concentrations of poly(I:C) and LPS. Some other 16HBE cells, before the co-stimulation of poly(I:C) and LPS, were pretreated with dexamethasone and p38MAPK specific inhibitor (SB203580), respectively. The levels of IL-8/CXCL8 and IP-10/CXCL1 mRNA transcription were detected by RT-PCR after 6 h challenge. The contents of IL-8 and IP-10 proteins were detected by ELISA after 24 h challenge. RESULTS: (1) The mRNA and protein expression of IL-8, not IP-10, increased under 10 µg/mL LPS stimulation compared with control group. The mRNA and protein expressions of both IL-8 and IP-10 were elevated significantly by the co-stimulation of LPS and 0.1 µg/mL poly (I:C) compared with control group and simple LPS groups. (2) The mRNA and protein expressions of IL-8 and IP-10 increased under the challenge of different concentrations of poly(I:C) (0.001, 0.01, 0.1 µg/mL) in a concentration-dependent manner, which showed no change after adding 10 µg/mL LPS. (3) Dexamethasone (1 µmol/L) and SB203580 (20 µmol/L) significantly decreased both the mRNA and protein production of IL-8 and IP-10 induced by co-stimulation of 0.1 µg/mL poly (I:C) and 10 µg/mL LPS compared with the control group and control+DMSO group respectively (P<0.01 and P<0.05). Inhibitive effect of dexamethasone was stronger than that of p38MAPK inhibitor. CONCLUSIONS: The co-stimulation of poly(I:C) and LPS can induce chemokine expression of airway epithelial cells. Poly(I:C) enhances the IL-8 expression induced by single LPS challenge, which suggests that viral infection could enhance the inflammation resulted from bacterial colonization in airway. Glucocorticoid has the greater effect on the inhibition of chemotactic factors production than p38MAPK inhibitor. These two drugs have a potential therapeutic effect on AECOPD caused by viral infection.

[Bronchoscopic cryotherapy combined with drugs infusion in the treatment of transbronchial tuberculous].

OBJECTIVE: To summarize the bronchoscopic features of transbronchial tuberculous mediastinal lymphadenitis and to observe the clinical efficacy of cryotherapy combined with drug infusion through bronchoscope. METHODS: Twenty-three cases of tuberculous mediastinal lymphadenitis diagnosed at Changhai Hospital were retrospectively analyzed. The bronchoscopic manifestations and the times, course, efficacy, complications and recurrence rate after treatment with cryotherapy combined with drug infusion were described. RESULTS: The mean age of the patients was (31 ± 10) years and the male to female ratio was 1:1.9. A total of 41 transmural lymph node lesions were found, usually after (3.4 ± 0.6) months with systemic anti-tuberculosis chemotherapy. The lesions occurred at the right side in 21 cases (60.98%). Endoscopic manifestations included caseous necrosis, granulomatous nodules, or both simultaneously, some lesions containing anthracotic substances. The median treatments of cryotherapy and drug infusion were 3 (1 - 6) times and 8 (6 - 11) times respectively. No significant difference was found between multiple lesions and single lesion group in the treatment of combination therapy. Therapeutic efficacy was 38/41 with improvement of bronchoscopic manifestations to smooth mucosa, lumen patency, mild anthracotic pigmentation or scar tissue. The rate of complications which included local bleeding and mediastinal bronchial fistula was 3.59%. No recurrence occurred in a long-term follow-up period. CONCLUSION: Combination of cryotherapy and drug infusion through bronchoscope is a simple, safe and effective method to treat transbronchial tuberculous mediastinal lymphadenitis.