Learning from low-rank multimodal representations for predicting disease-drug associations.

BACKGROUND: Disease-drug associations provide essential information for drug discovery and disease treatment. Many disease-drug associations remain unobserved or unknown, and trials to confirm these associations are time-consuming and expensive. To better understand and explore these valuable associations, it would be useful to develop computational methods for predicting unobserved disease-drug associations. With the advent of various datasets describing diseases and drugs, it has become more feasible to build a model describing the potential correlation between disease and drugs. RESULTS: In this work, we propose a new prediction method, called LMFDA, which works in several stages. First, it studies the drug chemical structure, disease MeSH descriptors, disease-related phenotypic terms, and drug-drug interactions. On this basis, similarity networks of different sources are constructed to enrich the representation of drugs and diseases. Based on the fused disease similarity network and drug similarity network, LMFDA calculated the association score of each pair of diseases and drugs in the database. This method achieves good performance on Fdataset and Cdataset, AUROCs were 91.6% and 92.1% respectively, higher than many of the existing computational models. CONCLUSIONS: The novelty of LMFDA lies in the introduction of multimodal fusion using low-rank tensors to fuse multiple similar networks and combine matrix complement technology to predict potential association. We have demonstrated that LMFDA can display excellent network integration ability for accurate disease-drug association inferring and achieve substantial improvement over the advanced approach. Overall, experimental results on two real-world networks dataset demonstrate that LMFDA able to delivers an excellent detecting performance. Results also suggest that perfecting similar networks with as much domain knowledge as possible is a promising direction for drug repositioning.

Effect of Combined Statin and Antihypertensive Therapy in Patients with Hypertension: A Systematic Review and Meta-Analysis.

INTRODUCTION: This meta-analysis aimed to explore the preventive effects of combined statin and antihypertensive therapy on major cardiovascular outcomes in patients with hypertension. METHODS: PubMed, Embase, and the Cochrane Library databases and reference lists of published studies were systematically searched throughout October 9, 2019. Studies designed as randomized controlled trials and investigating the effects of combined statin and antihypertensive therapy versus antihypertensive therapy alone were included. Data abstraction and quality of included studies were assessed by 2 independent authors. The summary results were calculated using relative risks (RRs) with 95% CIs employing a random-effects model. RESULTS: A total of 8 randomized controlled trials including 38,618 patients were finally enrolled. The summary RRs indicated that the combined therapy significantly reduced the risk of major adverse cardiovascular events compared with antihypertensive therapy alone (RR 0.79; 95% CI 0.71-0.88; p < 0.001). Furthermore, the patients in the combined therapy group also experienced less myocardial infarction (RR 0.67; 95% CI 0.53-0.84; p = 0.001) and stroke risks (RR 0.82; 95% CI 0.72-0.94; p = 0.005), while no significant difference was observed between combined therapy and antihypertensive therapy alone regarding cardiac death (RR 0.96; 95% CI 0.84-1.08; p = 0.465) and all-cause mortality (RR 0.95; 95% CI 0.86-1.04; p = 0.277). CONCLUSION: These findings suggested that combined statin and antihypertensive therapy was associated with more cardiovascular benefits compared with antihypertensive therapy alone.

Effect of Combined Antihypertensive and Lipid-Lowering Therapies on Cognitive Function: A New Treatment Strategy?

Risk factors for cardiovascular disease such as hypertension and hyperlipidemia are associated with cognitive decline. However, there is still no clear evidence that the use of antihypertensive or lipid-lowering therapy can prevent or delay cognitive decline or development of dementia. To provide a reference for clinical treatment, we analyzed the potential mechanisms of cognitive dysfunction induced by hypertension and hyperlipidemia, the clinical research and controversy of antihypertensive and lipid-lowering therapies on cognitive function, and the clinical value of combined antihypertensive and lipid-lowering therapy. It is currently believed that hypertension and elevated blood cholesterol levels in middle-aged people may be related to cognitive impairment or dementia in the elderly. Some studies suggest that intensive antihypertensive or lipid-lowering therapies are better than standard antihypertensive or lipid-lowering therapy, yet further tests are needed to confirm their effects on cognitive function. Actively controlling potential risk factors from middle age may be important for Alzheimer's disease (AD) prevention.

Potential protective effects of red yeast rice in endothelial function against atherosclerotic cardiovascular disease.

Atherosclerotic cardiovascular disease (ASCVD) is the deadliest disease in the world, with endothelial injury occurring throughout the course of the disease. Therefore, improvement in endothelial function is of essential importance in the prevention of ASCVD. Red yeast rice (RYR), a healthy traditional Chinese food, has a lipid modulation function and also plays a vital role in the improvement of endothelial reactivity and cardiovascular protection; thus, it is significant in the prevention and treatment of ASCVD. This article reviews the molecular mechanisms of RYR and its related products in the improvement of endothelial function in terms of endothelial reactivity, anti-apoptosis of endothelial progenitor cells, oxidative stress alleviation and anti-inflammation.

Combined antihypertensive and statin therapy for the prevention of cardiovascular events in patients with hypertension without complications: protocol for a systematic review and meta-analysis.

INTRODUCTION: High blood pressure (BP) affects over 40% of adults over the age of 25 worldwide and is the leading global risk factor for death or disability. Hypertension is also the most important risk factor for endovascular atherosclerosis, which, when combined with other cardiovascular risk factors, leads to atherosclerotic cardiovascular disease (ASCVD). Statins are one of the most widely used drugs for the prevention of ASCVD. The recently announced study of Heart Outcomes Prevention Evaluation-3 suggests that cholesterol-lowering agents combined with antihypertensive therapy can prevent cardiovascular events and reduce the combined endpoint. We plan to conduct a systematic review and meta-analysis to evaluate whether combined antihypertensive and statin therapy is more beneficial than antihypertensive therapy alone in patients with hypertension without complications. METHODS AND ANALYSIS: We will perform a comprehensive search for randomised controlled trials evaluating combined antihypertensive and statin therapy for the treatment of patients with hypertension. The following English electronic databases will be searched: The Cochrane Library, EMBASE and PubMed. Outcomes will be categorised as short-term (≤6 months) or long-term (>6 months). When evaluating the effects of combined antihypertensive and statin therapy, a short-term outcome is usually defined as a change in BP or lipid levels, while a long-term outcome is usually defined as cardiovascular benefits or risks. The data screening and extraction will be conducted by two different reviewers. The quality of the RCTs will be assessed according to the Cochrane handbook risk of bias tool. ETHICS AND DISSEMINATION: This review does not require ethics approval and the results of the meta-analysis will be submitted to a peer-review journal. PROSPERO REGISTRATION NUMBER: CRD42017071935.

Association Between Plasma Homocysteine and Microalbuminuria in Untreated Patients with Essential Hypertension: a Case-Control Study.

BACKGROUND/AIMS: Kidney function is critical for homocysteine (Hcy) clearance, and plasma Hcy levels are frequently increased in patients with renal failure. Microalbuminuria (MAU) is an important marker of early renal damage caused by hypertension. At present, there is insufficient evidence on the relationship between Hcy and microalbuminuria. METHODS: This is a 1: 2 matched, hospital-based case-control study. At initial visit, out of 1535 outpatients with no prior history of medication, 450 qualified subjects were selected based on inclusion and exclusion criteria. The concentration of Hcy in the serum was evaluated using a cyclic enzyme method. MAU was defined by a urine albumin/creatinine ratio (UACR) between 30 µg/mg and 300 µg/mg. RESULTS: A total of 450 patients were included in this study (150 in the MAU group and 300 in the non-MAU group). The MAU group had higher mean systolic blood pressure (SBP), mean diastolic blood pressure (DBP), heart rate (HR) and plasma Hcy levels than did the non-MAU group. The area under the receiver operating characteristics (ROC) curves was 0.772 (95% CI: 0.724-0.819, P < 0.001) with a cut-off value of 15.0, and the sensitivity and specificity of Hcy in predicting the MAU status in hypertensive patients were 49.3% and 92.3%, respectively. Multiple logistic regression modelling suggested that patients with a higher Hcy level (> 15 µmol/L) were more likely to have MAU (95% CI: 5.650-16.543, P < 0.001). The other predictive factor for MAU was 24-h mean SBP (95% CI: 0.941-0.993, P = 0.015). CONCLUSION: This matched case-control study indicates that Hcy may increase the susceptibility of essential hypertensive subjects to MAU.

The importance of genetic counseling and genetic screening: a case report of a 16-year-old boy with resistant hypertension and severe hypokalemia.

Liddle's syndrome, an autosomal dominant form of monogenic hypertension, is characterized by salt-sensitive hypertension with early penetrance, hypokalemia, metabolic alkalosis, suppression of plasma rennin activity and aldosterone secretion, and a clear-cut response to epithelial sodium channel blockers but not spironolactone therapy. Here, we describe the case of a 16-year-old boy patient with resistant hypertension (maintain 170-180/100-110 mm Hg after administration four kinds of antiypertensive drugs) and severe hypokalemia. After a series of checks, we exclude primary aldosteronism and renal artery stenosis and other diseases. Finally, the Liddle syndrome was diagnosed because of the DNA sequencing found that the proband's mother and himself had mutations P616L (c.1847 C>T) in the SCNN1B gene. Liddle syndrome should be considered as a cause of hypertension in children or adolescents particularly with suppressed renin activity. Early diagnosis and appropriately tailored treatment avoid complications of long-term unrecognized or inappropriately managed hypertension. Genetic testing has made it possible to make accurate diagnoses and develop tailored therapies for mutation carriers. The role of genetic testing and genetic counseling in establishing the early diagnosis of Liddle's syndrome is important.

Ozone therapy induced sinus arrest in a hypertensive patient with chronic kidney disease: A case report.

RATIONALE: Ozone autohemotherapy as an alternative treatment method has been applied to the treatment of several diseases. Here, we report a patient used ozone autohemotherapy to treat her hypertension and diabetes. Nevertheless, the patient occurred sudden dizziness and black haze due to hyperkalemia. PATIENT CONCERNS: A 54-year-old woman who was admitted to our emergency department complaining of sudden dizziness and black haze for 5 hours. DIAGNOSES: The blood potassium test showed hyperkalemia. Upon further inquiry of her medical history, the patient received ozone autohemotherapy to treat hypertension and diabetes for 9 days prior to admission. INTERVENTIONS: The ozone therapy had been asked to stop. Insulin, sodium bicarbonate, and sodium polystyrene sulfonate were administered to the patient. OUTCOMES: After treatment, blood potassium remained in the normal range. After 3 days of treatment, the 24-hour dynamic electrocardiogram revealed sinus rhythm with an average heart rate of 82 beats/min, occasional ventricular premature beats, occasional ventricular premature beats, and no ST segment depression. LESSONS: Although ozone therapy is widely used in the treatment of several diseases, adverse reactions should be given attention in clinical practice, especially in patients with chronic kidney disease.

Value of Neutrophil Counts in Predicting Surgery-Related Acute Kidney Injury and the Interaction of These Counts With Diabetes in Chronic Kidney Disease Patients With Hypertension: A Cohort Study.

As a component of routine blood cell analyses, the quantity of neutrophils present is a proven predictor of morbidity and mortality in several clinical settings. However, whether episodes of acute kidney injury (AKI) are associated with higher neutrophil counts in vulnerable groups, such as chronic kidney disease (CKD) patients with hypertension, are unknown. This study was conducted to investigate the relationship between neutrophil counts and the incidence of surgery-related AKI in CKD patients with hypertension.This was a retrospective cohort study of the relationship between neutrophils and surgery-related AKI. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using logistic regression models.In total, 119 (11.9%) of 998 patients experienced surgery-related AKI during hospitalization from October 2008 to February 2013. We divided patients into 4 quartiles according to their neutrophil counts. After adjusting for multiple covariates, the patients in the 4th quartile of neutrophil counts had greater ORs for AKI compared to those in the 1st quartile. The incidence of AKI increased 1.59-fold for those patients with neutrophil counts ≥6.30 × 10/L. There was a positive linear association between the neutrophil count upon admission and the predicted probability of AKI. The cross-validation revealed a statistically significant predictive accuracy for AKI (area under the curve (AUC) = 0.68, 95% CI, 0.67-0.69). The interaction analyses revealed that higher neutrophil counts are associated with a heightened risk of AKI in the presence of diabetes (OR = 3.38, 95% CI, 1.06-10.80). There were no interactions between neutrophil counts and age (P = 0.371), sex (P = 0.335), estimated glomerular filtration rate (P = 0.487), systolic blood pressure (P = 0.950), diastolic blood pressure (P = 0.977), the presence of chronic heart failure (P = 0.226), or sepsis (P = 0.796).The neutrophil count upon admission, an index that is easily and rapidly measured, is valuable for the prediction of surgery-related AKI in CKD patients with hypertension, especially in those with diabetes.

Association between high-density lipoprotein cholesterol and renal function in elderly hypertension: a cross-sectional study in Chinese population.

Few studies have yet investigated the possible association between high-density lipoprotein cholesterol (HDL-C) and kidney function in elderly patients with primary hypertension. Accordingly, the aim of the present study was to evaluate the relationship between HDL-C and kidney function in elderly hypertension. A total of 14,644 elderly hypertensive subjects were enrolled in our cross-sectional study. The patients were categorized based on serum HDL-C level and glomerular filtration rate (GFR) value, respectively. One-way analysis of variance was used to compare the parameters among different groups. Bonferroni correction was performed for multiple comparisons. Analysis of covariance was used to control for confounding factors. The significance of difference between 3 groups and more was determined by chi-square test for categorical variables. Serum creatinine and uric acid were negatively related to HDL-C level, whereas GFR was positively related to HDL-C level in elderly hypertensive patients according to tertiles of HDL-C and tertiles of HDL-C/total cholesterol ratio (all P for trends <0.05). The male elderly hypertensive patients showed stronger relationship between HDL-C and renal function than the female elderly hypertensive subjects. Low HDL-C was associated with renal insufficiency and proteinuria in the hypertensive elderly (P < 0.05). The elderly "renal-hyperfiltrator" appeared to have lower HDL-C level, compared with the "normal renal-filtrator" (P < 0.05). There was an inverse "V" shape between HDL-C and GFR by GFR strata. Our results point out that there is an association of low HDL-C level with impaired kidney function in elderly hypertensive patients. Glomerular hyperfiltration may also affect HDL-C level and sex might be an influential factor for the association of HDL-C with kidney function in elderly hypertension.

Relationship between red blood cell distribution width and early-stage renal function damage in patients with essential hypertension.

BACKGROUND: Red cell distribution (RDW) has been suggested to be associated with cardiovascular mortality and mortality. However, few studies have yet investigated the possible association between RDW and early-stage renal function damage in patients with primary hypertension without receiving drug treatment. Accordingly, the aim of the present study was to evaluate early-stage renal function status in patients with RDW levels. RESULTS: The study included 513 primary hypertension patients (319 men and 194 women) without receiving drug treatment. Significant positive correlation was observed between albumin-to-creatinine ratio (ACR) and RDW in hypertensive patients (r = 0.531, P < 0.001). In multivariate line regression analysis, night-time SBP (B = 0.042, P < 0.001), ACR (B = 0.005, P < 0.001), and uric acid (B = 0.001, P = 0.022) were positive predictors of RDW independent of age, sex, hemoglobin, and other indexes, whereas daytime SBP (B = -0.019, P < 0.001) was inversely associated with RDW. The receiver operating characteristics curves (ROC) explored the relationship between renal function status and RDW, estimated glomerular filtration rate (eGFR), serum creatinine, and high-sensitivity C-reactive protein. The area under the curve was 0.81 (95% CI: 0.77-0.85; P < 0.001), 0.45 (95% CI: 0.39-0.50; P = 0.049), 0.49 (95% CI: 0.43-0.54; P = 0.583), and 0.49 (95% CI: 0.44-0.55; P = 0.811), respectively. Using a cutoff point of 12.8, the RDW predicted renal function status (ACR) with a sensitivity of 76% and a specificity of 70%. CONCLUSION: RDW, as an easy and quick measurable index, can predict early-stage renal function damage in essential hypertensive patients without receiving drug treatment.

[The effect of recombinant human interleukin-2 activated natural killer cells on angiogenesis and cardiac function in rats with experimental myocardial infarction].

OBJECTIVE: To investigate the effect of recombinant human interleukin-2 (rhIL-2) activated natural killer cells (rhIL-2-NK) on angiogenesis and cardiac function of rats with myocardial infarction (MI). METHODS: Natural killer cells (NKs) were isolated and activated by rhIL-2 in vitro. Untreated NKs were used as the control, the killing capacity of rhIL-2-NK were evaluated with cytotoxicity assay. Cardiac microvascular endothelial cells (CMECs) were cocultured with rhIL-2-NK. One hour after MI, rats were randomly divided into rhIL-2-NK group, NK group and blank control group and NK, rhIL-2-NK and PBS were injected directly in the infracted myocardium. At the 0, 1(st), 3(rd), 5(th), 7(th) and 20(th)th day after MI, the mRNA expression of monocyte chemotactic protein-1 (MCP-1), Tumor necrosis factor-α (TNF-α) and interleukin-2 (IL-2) were was detected by q-PCR essay. At the end of the therapy, the platelet endothelial cell adhesion molecule-1(CD31) and vascular endothelial growth factor (VEGF) were evaluated through immunohistochemical assay, and the cardiac function observed with echocardiography, homodynamic measurements. RESULTS: The NKs were isolated successfully and the CMEC were proliferated remarkably by coculturing with rhIL-2-NK (P < 0.01). The mRNA expression of MCP-1, TNF-α, CD31 and rhIL-2, VEGF were significantly upregulated in rhIL-2-NK group than in the PBS control group (P < 0.01). Four weeks after operation, LVEF was significantly higher in rhIL-2-NK group than in the PBS control group [(77.56 ± 15.67)% vs. (41.47 ± 12.21)%, P < 0.05)] and histomorphology assay revealed that the density of microvascular endothelial (MVD) of rhIL-2-NK group was significantly higher than that of PBS control group (17.35 ± 1.82 vs. 4.76 ± 0.92, P < 0.01). CONCLUSIONS: Myocardial injection of rhIL-2-NK could promote angiogenesis and improve cardiac function in MI rats.

The impact of blood pressure on kidney function in the elderly: a cross-sectional study.

BACKGROUND/AIMS: Intensive blood pressure (BP) target decreases blood perfusion of kidneys that attenuates the benefits of BP treatment in elderly hypertensive individuals. The optimal BP goal for renal function in the hypertensive elderly has been unclear. We investigated the impact of BP on renal function to define the appropriate BP target in the elderly. METHODS: A total of 28,258 elderly subjects were categorized into normotensive (Norm), hypotensive (Hypo) and hypertensive (Hyper) groups according to BP levels. Systolic, diastolic and pulse BP (SBP, DBP and PBP) were further stratified by 10 mmHg. Blood urea nitrogen, serum creatinine, uric acid, glomerular filtration rate (GFR), renal insufficiency prevalence (RIP) and proteinuria prevalence (PP) were compared among different groups and BP strata. The RIP and PP in the elderly with obesity, hyperlipidemia or diabetes in Norm, Hypo and Hyper groups were evaluated. RESULTS: GFR in Hypo and Hyper groups was significantly lower than that in Norm group. The RIP and PP was higher in Hypo and Hyper groups than that in the Norm group. Proteinuria became more prevalent when SBP was >140 mmHg or <90 mmHg. DBP>80 mmHg increased PP while DBP<70 mmHg increased RIP. PBP>60 mmHg led to an increased RIP and PP. Obesity or hyperlipidemia only combined with hypertension caused a significantly increased RIP and PP. Diabetes independent of hypertension contributed to higher RIP and PP. CONCLUSIONS: The most beneficial BP target for kidney function in the elderly may be SBP of 90-140 mmHg and DBP of 70-80 mmHg. PBP <60 mmHg may be appropriate.