Appraising the Causal Association between Systemic Iron Status and Heart Failure Risk: A Mendelian Randomisation Study.

Although observational studies have shown that abnormal systemic iron status is associated with an increased risk of heart failure (HF), it remains unclear whether this relationship represents true causality. We aimed to explore the causal relationship between iron status and HF risk. Two-sample Mendelian randomisation (MR) was applied to obtain a causal estimate. Genetic summary statistical data for the associations (p < 5 × 10−8) between single nucleotide polymorphisms (SNPs) and four iron status parameters were obtained from the Genetics of Iron Status Consortium in genome-wide association studies involving 48,972 subjects. Statistical data on the association of SNPs with HF were extracted from the UK biobank consortium (including 1088 HF cases and 360,106 controls). The results were further tested using MR based on the Bayesian model averaging (MR-BMA) and multivariate MR (MVMR). Of the twelve SNPs considered to be valid instrumental variables, three SNPs (rs1800562, rs855791, and rs1799945) were associated with all four iron biomarkers. Genetically predicted iron status biomarkers were not causally associated with HF risk (all p > 0.05). Sensitivity analysis did not show evidence of potential heterogeneity and horizontal pleiotropy. Convincing evidence to support a causal relationship between iron status and HF risk was not found. The strong relationship between abnormal iron status and HF risk may be explained by an indirect mechanism.

Analysis of the risk factors of linezolid-related haematological toxicity in Chinese patients.

WHAT IS KNOWN AND OBJECTIVES: Haematological toxicity including thrombocytopenia, anaemia and leucopenia is the main adverse events of linezolid (LZD) therapy. This study aimed to investigate the risk factors for LZD-induced haematological toxicity and define the threshold of plasma trough concentration to minimize the haematological toxicity. METHODS: 145 patients who received LZD for more than 10 days were retrospectively reviewed to determine the incidence of LZD-induced haematological toxicity. Meanwhile, the risk factors of haematological toxicity were confirmed by univariate and multivariate logistic regression analysis. RESULTS AND DISCUSSION: 9 (6.2%) patients developed leucopenia, while 52 (35.9%) and 26 (17.9%) patients developed thrombocytopenia and anaemia, respectively. The estimated glomerular filtration rate (eGFR) <90 ml/min/1.73 m2 (OR, 2.744; 95% CI, 1.117-6.734; p = 0.028) and baseline platelet count <200 × 109 /L (OR, 6.817; 95% CI, 2.870-16.193; p < 0.0001) were found to be significant risk factors for LZD-related thrombocytopenia. Aspartate aminotransferase (AST) >80 U/L (OR, 4.844; 95% CI, 1.207-19.451; p = 0.026) and eGFR <90 ml/min/1.73 m2 (OR, 7.132; 95% CI, 2.088-24.357; p = 0.002) were the risk factors for LZD-related anaemia. However, no significant risk factors were identified for LZD-related leucopenia. Moreover, LZD plasma trough concentration >8 mg/L [OR, 3.047; 95% CI, 1.233-7.539; p = 0.016] could be a predictor for the development of thrombocytopenia and anaemia. WHAT IS NEW AND CONCLUSION: Hepatic and/or renal dysfunction are the risk factors for LZD-related haematological toxicity, while the target plasma trough concentration within 8 mg/L via dose reduction could minimize the haematological toxicity induced by LZD.

Weighted gene co-expression network analysis identified underlying hub genes and mechanisms in the occurrence and development of viral myocarditis.

BACKGROUND: Myocarditis is an inflammatory myocardial disease, which may lead to heart failure and sudden death. Despite extensive research into the pathogenesis of myocarditis, effective treatments for this condition remain elusive. This study aimed to explore the potential pathogenesis and hub genes for viral myocarditis. METHODS: A weighted gene co-expression network analysis (WGCNA) was performed based on the gene expression profiles derived from mouse models at different stages of viral myocarditis (GSE35182). Functional annotation was executed within the key modules. Potential hub genes were predicted based on the intramodular connectivity (IC). Finally, potential microRNAs that regulate gene expression were predicted by miRNet analysis. RESULTS: Three gene co-expression modules showed the strongest correlation with the acute or chronic disease stage. A significant positive correlation was detected between the acute disease stage and the turquoise module, the genes of which were mainly enriched in antiviral response and immune-inflammatory activation. Furthermore, a significant positive correlation and a negative correlation were identified between the chronic disease stage and the brown and yellow modules, respectively. These modules were mainly associated with the cytoskeleton, phosphorylation, cellular catabolic process, and autophagy. Subsequently, we predicted the underlying hub genes and microRNAs in the three modules. CONCLUSIONS: This study revealed the main biological processes in different stages of viral myocarditis and predicted hub genes in both the acute and chronic disease stages. Our results may be helpful for developing new therapeutic targets for viral myocarditis in future research.

Carotid intima-media thickness and plagues are associated with indicators of peripheral artery diseases in patients with diabetes.

AIMS: We investigated associations of carotid intima-media thickness (CIMT) and carotid plaque with ankle-brachial index (ABI) and toe-brachial index (TBI) in Chinese adults. METHODS: A cross-sectional analysis was performed in 6688 participants from a well-defined Chinese community. CIMT and carotid plaque was measured with a high-resolution B-mode tomographic ultrasound system. Low ABI was defined as ABI ≤ 0.90. Low TBI was defined as TBI ≤ 0.60. Carotid plaques were classified as normal, homogeneous or heterogeneous according to morphology. RESULTS: After adjusting for age, sex and body mass index, each 0.10 mm CIMT increase was associated with 0.0123 unit decrease in TBI (P = 0.004) and 0.0063 in ABI (P = 0.04) in patients with diabetes. After further adjustments for waist circumference, smoking and drinking habits, hypertension, lipids and hemoglobin A1c, the associations between CIMT and TBI remained significant; while those with ABI were disappeared. Meanwhile, each 0.10 mm increment of CIMT or rank of carotid plaque morphology was associated with a risk of presence of low TBI (CIMT: odds ratio: 1.21, 95% confidence interval: 1.05-1.40; carotid plaque morphology: 1.45, 1.01-2.08) in patients with diabetes after adjustments. However, no associations were found between CIMT or carotid plaque morphology and TBI or ABI in non-diabetic participants. CONCLUSIONS: CIMT and carotid plaque morphology were significantly associated with TBI in patients with diabetes.

Worldwide research productivity in the field of psychiatry.

BACKGROUND: The field of psychiatry has seen significant progress in recent years due to worldwide contributions. National productivity, however, in the field of psychiatry is still unclear. In our study, we investigated contributions of individual nations to the field of psychiatry. METHODS: The Web of Science was used to perform a search from 2011 to 2015 on the subject category "psychiatry". The total number of articles, citations and the per capita numbers were obtained to analyze the contributions of different countries. RESULTS: In psychiatry journals from 2011 to 2015, 84,760 articles were published worldwide. The most productive world areas were North America, East Asia, Europe and Oceania. The percentage of articles published in high-income countries was 87.77%, middle-income countries published 12.07%, and lower-income published 0.16%. Most articles were published by the United States (32.68%); the United Kingdom was next (8.59%), which was followed by Germany (6.77%), Australia (5.87%), and Canada (4.9%). The country with the highest number of citations (243,394) was the United States. A positive correlation was found between the population/GDP and the number of publications (P < 0.01). Australia ranked the highest when normalized to population size, and the Netherlands and Norway were next. The Netherlands ranked highest, followed by Israel and Australia when adjusted for GDP. CONCLUSIONS: The authorship of most of the psychiatry articles was from high-income countries and few papers came from low-income countries. The most productive country was the United States. However, when normalized to population size and GDP, some European and Oceania countries were most productive.

[Changes of Microbial Community Structure in Activated Sludge Bulking at Low Temperature].

The mechanism of activated sludge bulking in Zhengzhou wastewater treatment plant was studied by measurement of water quality parameters and high-throughput sequencing technology. The change of SVI value was significantly negatively correlated with the seasonal temperature variation, and sludge bulking was easy to occur during December to the next April, but the water quality was not affected. The result verified by high-throughput sequencing technology analysis showed that the microbial community structure of bulking sludge was significantly different from that of the non-bulking one. The dominant filamentous bacteria in the bulking sludge in this plant were Saprospiraceae and Flavobacterium. Therefore, the activated sludge bulking in this wastewater treatment plant was caused by the propagation of filamentous bacteria at low temperature.

A myrsinol diterpene isolated from Euphorbia prolifera reverses multidrug resistance in breast cancer cells.

P-glycoprotein (P-gp), a member of ATP-Binding Cassette transporter superfamily, can expel a variety of anti-cancer drugs so that it impairs the effect of cancer chemotherapy and results in multidrug resistance (MDR). The P-gp inhibitors are important to circumvent MDR and improve efficacy of cancer chemotherapy. The dried root of Euphorbia prolifera Buch.-Ham. has been used to treat cancer and inflammation in Chinese folk medicine for several hundred years. A myrsinol diterpene derived from Euphorbia prolifera Buch.-Ham. (J196-9-4) could modulate multidrug resistance. Cytotoxicity assays were performed to measure the reversal efficiency of J196-9-4. Efflux assay and ATPase assay were used to elucidate the mechanism of the chemical. J196-9-4 potentiated cytotoxicity of anti-cancer drugs in the P-gp over-expressing resistant breast cancer cell line MCF-7/Adr as compared to MCF-7 cells. Concentrations of 5 and 10 µM J196-9-4 could reverse the resistance to daunorubicin, vincristine, and topotecan significantly. Since J196-9-4 inhibited P-gp mediated efflux and stimulated ATP hydrolysis, J196-9-4 was a substrate of P-gp. Thus J196-9-4 is a competitive inhibitor of P-gp and reverses multidrug resistance induced by the transporter.

A case of methylprednisolone treatment for interstitial pneumonia induced by gefitinibin.

In this case, an old man was diagnosed as lung cancer, clinical stage IV. In order to alleviate cancer, this patient was treated with gefitinib. Three months later, symptoms such as a significant weakness, chest tightness and shortness of breath after sports arised and intensifying. Implosive therapy with high dose methylprednisolone is used to control the weakness caused by gefitinib. Eight days after treatment, patient's condition significantly improved. The use of methylprednisolone can effectively treat interstitial pneumonia induced by gefitinibin, help patients get better from critical condition such as type I respiratory failure. This new discovery is a good guidance for clinical treatment of gefitinibin caused interstitial pneumonia.