Quantitative analysis of abdominal aortic blood flow by 99mTc-DTPA renal scintigraphy in patients with heart failure.

OBJECTIVE: This study aimed to explore the characteristics of abdominal aortic blood flow in patients with heart failure (HF) using 99mTc-diethylenetriaminepentaacetic acid (DTPA) renal scintigraphy. We investigated the ability of renal scintigraphy to measure the cardiopulmonary transit time and assessed whether the time-to-peak of the abdominal aorta (TTPa) can distinguish between individuals with and without HF. METHODS: We conducted a retrospective study that included 304 and 37 patients with and without HF (controls), respectively. All participants underwent 99mTc-DTPA renal scintigraphy. The time to peak from the abdominal aorta's first-pass time-activity curve was noted and compared between the groups. The diagnostic significance of TTPa for HF was ascertained through receiver operating characteristic (ROC) analysis and logistic regression. Factors influencing the TTPa were assessed using ordered logistic regression. RESULTS: The HF group displayed a significantly prolonged TTPa than controls (18.5 [14, 27] s vs. 11 [11, 13] s). Among the HF categories, HF with reduced ejection fraction (HFrEF) exhibited the longest TTPa compared with HF with mildly reduced (HFmrEF) and preserved EF (HFpEF) (25 [17, 36.5] s vs. 17 [15, 23] s vs. 15 [11, 17] s) (P < 0.001). The ROC analysis had an area under the curve of 0.831, which underscored TTPa's independent diagnostic relevance for HF. The diagnostic precision was enhanced as left ventricular ejection fraction (LVEF) declined and HF worsened. Independent factors for TTPa included the left atrium diameter, LVEF, right atrium diameter, velocity of tricuspid regurgitation, and moderate to severe aortic regurgitation. CONCLUSIONS: Based on 99mTc-DTPA renal scintigraphy, TTPa may be used as a straightforward and non-invasive tool that can effectively distinguish patients with and without HF.

Characteristics of Lumbar Bone Density in Middle-Aged and Elderly Subjects: A Correlation Study between T-Scores Determined by the DEXA Scan and Hounsfield Units from CT.

Purpose: To describe the characteristics of lumbar bone density in middle-aged and elderly subjects and explore whether there is a correlation between computed tomography (CT) values and the bone mineral density (BMD) T-scores of the lumbar vertebral cancellous bone. Methods: Forty-two subjects, including 25 males and 17 females, with a mean age of 56 years, who underwent BMD measurement and lumbar multislice spiral CT scan at the China Rehabilitation Research Center from January 2019 to December 2019 were selected. Dual-energy X-ray absorptiometry (DEXA) was applied to obtain the total BMD T-scores of the lumbar L1-L4 vertebrae. Results: The CT values decreased from L1 to L4 and were 145.91 ± 8.686 HU, 143.18 ± 8.598 HU, 137.39 ± 8.276 HU, and 135.23 ± 8.219 HU, respectively. The total CT value of L1-L4 was 140.43 ± 4.199 HU. The mean total BMD T-score of L1-L4 was -0.94. The CT values of the L1-L4 vertebrae were positively correlated with the total BMD T-scores of L1-L4 (r = 0.349, P < 0.001). The CT value of the left third of the same vertebrae was the highest, and there was a strong positive correlation between the regional CT value of the lumbar spine and the entire vertebra CT values (r > 0.7). Conclusion: The CT values of the lumbar spine can assist the measurement of the T-scores of lumbar BMD, which could aid in early opportunistic screening for osteopenia and preventing osteoporosis and vertebral compression fractures in middle-aged and elderly subjects. This trial is registered with ChiCTR2100049571.

Silencing ferritin alleviates atherosclerosis in mice via regulating the expression levels of matrix metalloproteinases and interleukins.

This study was conducted to investigate the roles of ferritin in atherosclerosis. The mouse model of atherosclerosis was established by feeding ApoE knockout mice with a high-fat diet. The mice were then treated with ferritin-overexpressing and -silencing constructs, and assessed for interleukins (ILs) and matrix metalloproteinases (MMPs) levels using ELISA and Western blot analysis. After being fed with a high-fat diet, the ApoE knockout mice developed pro-atherogenic lipid profiles with elevated total cholesterol (TC), triglyceride (TG) and low-density lipoprotein cholesterol (LDL-C). They also showed increased atherosclerotic lesions including narrowed lumen diameter, reduced lumen area, and increased plaque size. Following injection of the overexpression and silencing constructs, mRNA levels of ferritin were increased and decreased, respectively, and at the same time the atherosclerotic lesions were aggravated and alleviated, respectively. Further analysis indicated that silencing of ferritin gene reduced IL-1ß and IL-10 levels while overexpressing ferritin increased them. On other hand, the TNF-α levels showed an opposite trend. MMP8, MMP12 and MMP13 levels were increased or decreased significantly after the mice were injected with ferritin over-expression or silencing vectors, respectively. Western blot analysis showed that compared to the control, overexpressing ferritin resulted in increased expression of p-JNK while silencing ferritin decreased the expression. Meanwhile, the levels of pc-Jun remained unchanged. Our work demonstrates that ferritin can regulate the progress of atherosclerosis via regulating the expression levels of MMPs and interleukins. Silencing ferritin inhibits the development of atherosclerosis and is, therefore, worth being further investigated as a potential therapeutic approach for this disease.

The Impact of Glucocorticoid Therapy on Guideline-Directed Medical Treatment Titration in Patients Hospitalized for Heart Failure with Low Blood Pressure: A Retrospective Study.

BACKGROUND: Positive inotropic and renal protective actions of glucocorticoids have been observed clinically. Therefore, glucocorticoids may be used in patients with heart failure and low blood pressure (HF-LBP). METHODS: The medical records of 144 consecutive patients with HF-LBP who received glucocorticoids as an adjunctive treatment to facilitate the up-titration of ß-blocker and angiotensin-converting enzyme inhibitor were reviewed. RESULTS: After four weeks of treatment, the metoprolol and captopril (or equivalent) dosages were progressively and consistently increased from 25 (interquartile range [IQR] = 12.5-75 mg/day) to 100 mg/day (IQR = 50-178.8 mg/day) and from 0 (IQR = 0-25 mg/day) to 12.5 mg/day (IQR = 0-50 mg/day), respectively. There was a remarkable beneficial hemodynamic response to the glucocorticoid treatment signified by an increase in blood pressure and decrease in heart rate. The average heart rate decreased by 6 beat per minute (bpm) (0.5-16 bpm), and the mean arterial blood pressure increased from 74.06 ± 7.81 to 78.85 ± 7.91 mmHg. We also observed an improvement in renal function and an increased diuretic response following glucocorticoid treatment. As a result, the left ventricular ejection fraction increased from 28.92 ± 8.06% to 33.86 ± 8.76%, and the diuretic response increased from 776.7 mL/40 mg furosemide (IQR = 133.8-2000 mL) to 4000 mL/40 mg furosemide on day 28 (IQR = 2200-5925 mL). CONCLUSION: The use of glucocorticoid treatment to maintain hemodynamic and renal functional targets when titrating guideline-directed medical treatment in patients with HF-LBP may be safe, effective, and feasible.

Mendelian randomization analysis identified genes pleiotropically associated with the risk and prognosis of COVID-19.

OBJECTIVES: COVID-19 has caused a large global pandemic. Patients with COVID-19 exhibited considerable variation in disease behavior. Pervious genome-wide association studies have identified potential genetic variants involved in the risk and prognosis of COVID-19, but the underlying biological interpretation remains largely unclear. METHODS: We applied the summary data-based Mendelian randomization (SMR) method to identify genes that were pleiotropically associated with the risk and various outcomes of COVID-19, including severe respiratory confirmed COVID-19 and hospitalized COVID-19. RESULTS: In blood, we identified 2 probes, ILMN_1765146 and ILMN_1791057 tagging IFNAR2, that showed pleiotropic association with hospitalized COVID-19 (ß [SE]=0.42 [0.09], P = 4.75 × 10-06 and ß [SE]=-0.48 [0.11], P = 6.76 × 10-06, respectively). Although no other probes were significant after correction for multiple testing in both blood and lung, multiple genes as tagged by the top 5 probes were involved in inflammation or antiviral immunity, and several other tagged genes, such as PON2 and HPS5, were involved in blood coagulation. CONCLUSIONS: We identified IFNAR2 and other potential genes that could be involved in the susceptibility or prognosis of COVID-19. These findings provide important leads to a better understanding of the mechanisms of cytokine storm and venous thromboembolism in COVID-19 and potential therapeutic targets for the effective treatment of COVID-19.

Mendelian randomization analysis identified genes pleiotropically associated with the risk and prognosis of COVID-19.

OBJECTIVES: COVID-19 has caused a large global pandemic. Patients with COVID-19 exhibited considerable variation in disease behavior. Pervious genome-wide association studies have identified potential genetic variants involved in the risk and prognosis of COVID-19, but the underlying biological interpretation remains largely unclear. METHODS: We applied the summary data-based Mendelian randomization (SMR) method to identify genes that were pleiotropically associated with the risk and various outcomes of COVID-19, including severe respiratory confirmed COVID-19 and hospitalized COVID-19. RESULTS: In blood, we identified 2 probes, ILMN_1765146 and ILMN_1791057 tagging IFNAR2, that showed pleiotropic association with hospitalized COVID-19 (Beta; [SE]=0.42 [0.09], P=4.75E-06 and Beta; [SE]=-0.48 [0.11], P=6.76E-06, respectively). Although no other probes were significant after correction for multiple testing in both blood and lung, multiple genes as tagged by the top 5 probes were involved in inflammation or antiviral immunity, and several other tagged genes, such as PON2 and HPS5, were involved in blood coagulation. CONCLUSIONS: We identified IFNAR2 and other potential genes that could be involved in the susceptibility or prognosis of COVID-19. These findings provide important leads to a better understanding of the mechanisms of cytokine storm and venous thromboembolism in COVID-19 and potential therapeutic targets for the effective treatment of COVID-19.

The association between apolipoprotein E and gallstone disease: an updated meta-analysis.

BACKGROUND: Gallstone disease (GSD) is a common biliary tract disease worldwide. Previous studies have investigated the association of apolipoprotein E (APOE) E4 with GSD and reported inconsistent results. METHODS: In this paper, we conducted meta-analyses to examine whether APOE E4 is associated with the risk of GSD. A systematic literature search was performed in PubMed, Cochrane Library, EMBASE, and Google Scholar using the following inclusion criteria: 1) Studies on human subjects; 2) subjects in the control group must undergo ultrasound GSD screening, and presence of GSD in the experiment group can be clearly determined, e.g., diagnosis of GSD through ultrasound screening or a previous history of cholecystectomy or cholelithiasis; 3) the studies reported APOE genotype data (APOE E4+ vs. E4-) for subjects with and without GSD. In all the meta-analyses, we used random-effects models to calculate the odds ratios (ORs) as a measure of association as well as the corresponding confidence intervals (CIs). RESULTS: Our literature search found 13 publications with 14 studies, including a total of 1632 GSD patients and 5001 controls, that met the eligibility criteria and were included in the meta-analyses. We did not find a significant association between APOE E4 and risk of GSD (OR = 1.23, 95% CI: 0.89-1.68; p = 0.205). No significant associations were observed in subgroup analyses by gender and mean age. We obtained similar insignificant findings if an additive model was used, if subjects who had E2E4 genotype were excluded, or if low-quality studies were excluded. CONCLUSION: Our meta-analysis found insufficient evidence for the effect of APOE E4 on GSD risk. Future studies with large sample sizes that control for important confounding/risk factors are needed to validate our findings and to explore other genetic loci that might affect GSD risk.

Is the relationship between social support and depressive symptoms mediated by hope among Chinese central nervous system tumor patients?

BACKGROUND: It is common for central nervous system (CNS) tumor patients to suffer from depressive symptoms. If unrecognized or untreated, CNS tumors may lead to many serious problems in these patients. This study examines the association of social support with depressive symptoms in CNS tumor patients and explores the extent to which hope mediates this relationship. METHODS: A total of 269 CNS tumor patients in China were included in this study. We assessed depressive symptoms using the Epidemiologic Studies Depression Scale (CES-D), social support using the Perceived Social Support Scale (PSSS), and hope using the Herth Hope Index (HHI). Questionnaires were distributed to collect these data. Hierarchical linear regression analyses explored the interrelationship between social support, hope, and depressive symptoms. RESULTS: After adjustment for demographic characteristics, patients with less social support exhibited more depressive symptoms (ß = - 0.452, P < 0.01). Social support explained 19.1% of the variance in depressive symptoms. After adding hope to the regression model, the effect size for social support was reduced by over half but remained significant (from ß = - 0.452 to ß = - 0.218, P < 0.01). In addition, a lower level of hope (ß = - 0.386, P < 0.01) was associated with more depressive symptoms, and this measure explained an additional 9.3% of the variance in depressive symptoms. CONCLUSIONS: Much of the relationship between social support and depressive symptoms is explained by hope. Thus, interventions boosting both social support and hope help to reduce depressive symptoms in patients with CNS tumors.

Prevalence and associated positive psychological variables of anxiety and depression among patients with central nervous system tumors in China: a cross-sectional study.

BACKGROUND: Anxiety and depression have been identified as common psychological distresses faced by the majority of patients with cancer. However, no studies have investigated the relationship between positive psychological variables (hope, optimism and general self-efficacy) and anxiety and depression among patients with central nervous system (CNS) tumors in China. Our hypothesis is that the patients with higher levels of hope, optimism or general self-efficacy have lower levels of anxiety and depression when encountered by stressful life events such as CNS tumors. METHODS: Questionnaires, including the Hospital Anxiety and Depression Scale, the Herth Hope Index, the Life Orientation Scale-Revised and the General Self-Efficacy Scale, and demographic and clinical records were used to collect information about patients with CNS tumors in Liaoning Province, China. The study included 222 patients (effective response rate: 66.1%). Hierarchical linear regression analyses were performed to explore the associations among hope, optimism, general self-efficacy and anxiety/depression. RESULTS: Prevalence of anxiety and depression were 42.8 and 32.4%, respectively, among patients with CNS tumors. Hope and optimism both were negatively associated with anxiety and together accounted for 21.4% of variance in anxiety. Similarly, hope and optimism both were negatively associated with depression and accounted for 32.4% of variance in depression. CONCLUSIONS: The high prevalence of anxiety and depression among patients with CNS tumors should receive more attention in Chinese medical settings. To help reduce anxiety and depression, health care professionals should develop interventions to promote hope and optimism based on patients' specific needs.

The Association Between Genetic Polymorphism rs703842 in CYP27B1 and Multiple Sclerosis: A Meta-Analysis.

Multiple sclerosis (MS) is the most frequent nontraumatic disabling neurological disease among young adults. Previous studies have examined the association of rs703842 in CYP27B1 with MS susceptibility, with inconsistent results reported.The objective of this study is to conduct a systematic literature search and perform meta-analyses to examine whether rs703842 is associated with MS risk.We searched potential literature in PubMed, Cochrane Library, Embase, Google Scholar, Web of Science, and HuGE by using the following inclusion criteria: studies were on human subjects; the studies were case-control studies; studies included subjects who had MS and those who did not have MS; and the studies provided genotype data for rs703842 for subjects who had and did not have MS, or provided odds ratios (ORs) and the 95% confidence intervals (CIs) for assessing the association of rs703842 with MS, or provided sufficient data for the calculation of OR and the 95% CI. We used random-effects models to calculate the OR as a measure of association. We used I to assess between-study heterogeneity, and a funnel plot and Egger test to assess publication bias.Seven studies published since 2008 met the eligibility criteria and were included in the meta-analyses. We found that the C allele was significantly associated with reduced MS susceptibility (OR = 0.88, 95% CI: 0.80-0.89; P < 0.0001). We also found significant association of rs703842 with MS risk using a dominant and a recessive model (both P < 0.0002). Our results remain unchanged if our meta-analysis was limited to studies that included only Caucasian participants (OR = 0.85, 95% CI: 0.80-0.90; P < 0.0001).Our study has several limitations: The sample size is limited; We were unable to control for some important confounding factors as data for individual participant were not available; and Most of the included studies focus on MS risk in Caucasian. As a result, we could not perform meta-analysis for assessing the relationship in other ethnic groups.In summary, we found that the genetic variant rs703842 in CYP27B1 is associated with MS risk in Caucasians. More studies with larger sample size that control for important confounding factors are needed to validate the findings from this study.

Pregnane receptor gene polymorphisms, pathogenic bacteria distribution and drug sensitivity, and TCM syndrome differentiation in patients with cholelithiasis.

OBJECTIVE: To investigate the distribution of pathogens and drug resistance in bile and the association between the pregnane X receptor (PXR) gene polymorphisms, traditional Chinese medicine (TCM) syndromes and the risk of cholesterol gallstone disease (CGD). METHODS: A total of 392 samples were enrolled in this study from January 2014 to February 2015, among which 192 patients were with CGD, and 200 samples were healthy. Strains were isolated and susceptibility testing was the disk diffusion method susceptibility testing. The patients were divided into hepatochlic hygropyrexia, stagnation of liver-qi, and the accumulation of damp. The PXR gene polymorphisms were analyzed by polymerase chain reaction-restriction fragment length polymorphism. The association between the PXR gene polymorphisms and the risk of CGD was examined by logistic regression analysis. RESULTS: A total of 192 cases were detected in 230 of bile culture pathogens, including Gram-negative bacteria 133 (57.83%), Gram-positive bacteria 76 (33.04%), and fungi 21 (9.13%). The top five pathogens were Escherichia coli, Klebsiella pneumoniae, Enterococcus faecalis, Candida albicans, and Enterococcus feces, of which 110 cases was of single infection, 48 cases of mixed infection of two strains, eight cases of mixed infection of three bacteria. Among 59 Escherichia coli, the yield extended-spectrum beta-lactamases had 40 (67.80%). The hepatochlic hygropyrexia was the most TCM syndrome, followed by stagnation of liver-qi, and the accumulation of damp was least. Different pathogens and the rs6785049 genotypes distributed differently in cholelithiasis patients with different TCM syndromes (P < 0.05). In hepatochlic hygropyrexia patients the Gram-negative bacteria was most. There was significant differences between CGD group and control group in rs6785049 (P < 0.001). Comparison with wild-type portable GG, GA genotype increased the risk of the occurrence of gallstones (OR = 0.40, 95%CI: 0.16-0.79); likewise, carrying the GA+AA genotype also increased the risk (OR = 0.38, 95%CI: 0.19-0.81). There was no significant differences in rs2276707, rs3814055 site polymorphic loci alleles in CGD group and control group. CONCLUSIONS: In the treatment of cholelithiasis, bile samples should be collected for bacterial culture and sensitivity test, and drugs should be strictly chosen based on the results. The rs6785049 polymorphisms in PXR gene may increase the risk of gallstones ontogeny, and gallstones can be early detected and prevented by detecting genotypes. rs6785049 polymorphisms in PXR gene may has relationship with TCM syndromes.

The Association Between Genetic Variants in the Dopaminergic System and Posttraumatic Stress Disorder: A Meta-Analysis.

Posttraumatic stress disorder (PTSD) is a complex mental disorder and can severely interfere with the normal life of the affected people. Previous studies have examined the association of PTSD with genetic variants in multiple dopaminergic genes with inconsistent results. To perform a systematic literature search and conduct meta-analysis to examine whether genetic variants in the dopaminergic system is associated with PTSD. Data Sources: PubMed, Cochrane Library, Embase, Google Scholar, and HuGE. Study eligibility criteria and participants: The studies included subjects who had been screened for the presence of PTSD; the studies provided data for genetic variants of genes involved in the dopaminergic system; the outcomes of interest included diagnosis status of PTSD; and the studies were case-control studies. Study appraisal and synthesis methods: Odds ratio was used as a measure of association. We used random-effects model in all the meta-analyses. Between-study heterogeneity was assessed using I², and publication bias was evaluated using Egger test. Findings from meta-analyses were confirmed using random-effects meta-analyses under the framework of generalized linear model (GLM). A total of 19 studies met the eligibility criteria and were included in our analyses. We found that rs1800497 in DRD2 was significantly associated with PTSD (OR = 1.96, 95% CI: 1.15-3.33; P = 0.014). The 3'-UTR variable number tandem repeat (VNTR) in SLC6A3 also showed significant association with PTSD (OR = 1.62, 95% CI: 1.12-2.35; P = 0.010), but there was no association of rs4680 in COMT with PTSD (P = 0.595). Sample size is limited for some studies; type and severity of traumatic events varied across studies; we could not control for potential confounding factors, such as age at traumatic events and gender; and we could not examine gene-environment interaction due to lack of data. We found that rs1800497 in DRD2 and the VNTR in SLC6A3 showed significant association with PTSD. Future studies controlling for confounding factors, with large sample sizes and more homogeneous traumatic exposure, are needed to validate the findings from this study.

The Association Between Apolipoprotein E and Functional Outcome After Traumatic Brain Injury: A Meta-Analysis.

Traumatic brain injury (TBI) is a leading cause of death and disability. Previous studies have investigated the association of apolipoprotein E (APOE) ε4 with functional outcome after TBI and reported inconsistent results.The purpose of this study was to perform a systematic literature search and conduct meta-analyses to examine whether APOE ε4 is associated with poorer functional outcome in patients with TBI.We performed a systematic literature search in PubMed, Cochrane Library, Embase, Google Scholar, and HuGE.The eligibility criteria of this study included the following: Patients had TBI; the studies reported APOE genotype data or provided odds ratios (ORs) and the corresponding 95% confidence intervals (CIs); the functional outcome was assessed using the Glasgow Outcome Scale (GOS) or the Glasgow Outcome Scale Extended (GOSE); and patients were followed for at least 3 months after TBI.In all meta-analyses, we used random-effects models to calculate the odds ratio as a measure of association. We examined the association of APOE ε4 with functional outcome at different time points after TBI.A total of 12 studies met the eligibility criteria and were included in the meta-analyses. We did not find a significant association between APOE ε4 and functional outcome at 6 (P = 0.23), 12 (P = 0.44), and 24 months (P = 0.85) after TBI. However, APOE ε4 was associated with an increased risk of unfavorable long-term (≥6 months) functional outcome after TBI (OR = 1.36, 95% CI: 1.07-1.74, P = 0.01).Limitations of this study include The sample size was limited; the initial severity of TBI varied within and across studies; we could not control for potential confounding factors, such as age at injury and sex; a meta-analysis of the genotype dosage effect was not feasible; and we could not examine the association with specific factors such as neurobehavioral or specific cognitive functions.Our meta-analysis indicates APOE ε4 is associated with the long-term functional outcome of patients with TBI. Future studies that control for confounding factors, with large sample sizes and more homogeneous initial TBI severity levels, are needed to validate the findings from this study.

Silymarin attenuates paraquat-induced lung injury via Nrf2-mediated pathway in vivo and in vitro.

The present study aims to investigate the impacts and mechanisms of silymarin on paraquat (PQ)-induced lung injury in vivo and in vitro. In in vivo experiments, a total of 32 male Sprague-Dawley (SD) rats were randomly divided into four groups. The rats were killed on day 3. Histopathological changes in lung tissue were examined using HE and Masson's trichrome staining. Biomarkers of neutrophil activation, pulmonary oedema, pulmonary fibrosis, lung permeability and oxidative stress were detected. Several proinflammatory mediators and antioxidant related proteins were measured. In in vitro experiments, A549 cells were transfected with Nrf2 special siRNA to investigate the roles of Nrf2. The results show that silymarin administration abated PQ-induced lung histopathologic changes, decreased inflammatory cell infiltration and lung wet weight/dry weight (W/D) ratio, suppressed myeloperoxidase (MPO) activity and nitric oxide (NO)/inducible nitric oxide synthases (iNOS) expression, downregulated hydroxyproline (HYP) levels, reduced total protein concentration and proinflammatory mediator release, and improved oxidative stress (malondialdehyde, MDA; superoxide dismutase, SOD; catalase, CAT; and glutathione peroxidase, GSH-Px) in lung tissue and serum. Meanwhile, treatment with silymarin upregulated the levels of nuclear factor-erythroid-2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1) and NAD(P)H:quinone oxidoreductase-1(NQO1). However, the addition of Nrf2 siRNA reduced the expression of Nrf2-mediated antioxidant protein HO-1 and thus reversed the protective effects of silymarin against oxidative stress and inflammatory response. These results suggest that silymarin may exert protective effects against PQ-induced lung injury. Its mechanisms were associated with the Nrf2-mediated pathway. Therefore, silymarin may be a potential therapeutic drug for lung injury.

Effect of Corticosteroid on Renal Water and Sodium Excretion in Symptomatic Heart Failure: Prednisone for Renal Function Improvement Evaluation Study.

BACKGROUND: Recent evidence indicates that prednisone can potentiate renal responsiveness to diuretics in heart failure (HF). However, the optimal dose of prednisone is not known. METHOD: Thirty-eight patients with symptomatic HF were randomized to receive standard HF care alone (n = 10) or with low-dose (15 mg/d, n = 8), medium-dose (30 mg/d, n = 10), or high-dose prednisone (60 mg/d, n = 10), for 10 days. During this time, we recorded the 24-hour urinary output and the 24-hour urinary sodium excretion, at baseline, on day 5 and day 10. We also monitored the change in the concentration of serum creatinine, angiotensin II, aldosterone, high-sensitive C-reactive protein, tumor necrosis factor-α, interleukin 1ß, and interleukin 6. RESULTS: Low-dose prednisone significantly enhanced urine output. However, the effects of medium- and high-dose prednisone on urine output were less obvious. As for renal sodium excretion, high-dose prednisone induced a more potent natriuresis than low-dose prednisone. Despite the potent diuresis and natriuresis induced by prednisone, serum creatinine, angiotensin II, and aldosterone levels were not elevated. These favorable effects were not associated with an inflammatory suppression by glucocorticoids. CONCLUSIONS: Only low-dose prednisone significantly enhanced urine output. However, high-dose prednisone induced a more potent renal sodium excretion than low-dose prednisone.

Prednisone in Uric Acid Lowering in Symptomatic Heart Failure Patients with Hyperuricemia -- The PUSH-PATH3 Study.

OBJECTIVE: To determine the safety and efficacy of prednisone in patients with symptomatic heart failure (HF) and hyperuricemia. METHODS: Prednisone therapy was administered for a short time to 191 symptomatic HF patients with hyperuricemia (serum uric acid > 7 mg/dl). RESULTS: Prednisone significantly reduced serum uric acid by 2.99 mg/dl (p < 0.01) and serum creatinine by 0.17 mg/dl (p < 0.01). These favorable effects were associated with a remarkable increase in urine output, improvement in renal function, and improvement in clinical status. CONCLUSION: Prednisone can be used safely in symptomatic HF patients with hyperuricemia.

Association of genetic variants in and promoter hypermethylation of CDH1 with gastric cancer: a meta-analysis.

Gastric cancer (GC) is a common cause of cancer-related death. The etiology and pathogenesis of GC remain unclear, with genetic and epigenetic factors playing an important role. Previous studies investigated the association of GC with many genetic variants in and promoter hypermethylation of E-cadherin gene (CDH1), with conflicting results reported.To clarify this inconsistency, we conducted updated meta-analyses to assess the association of genetic variants in and the promoter hypermethylation of CDH1 with GC, including C-160A (rs16260) and other less-studied genetic variants,Data sources were PubMed, Cochrane Library, Google Scholar, Web of Knowledge, and HuGE, a navigator for human genome epidemiology.Study eligibility criteria and participant details are as follows: studies were conducted on human subjects; outcomes of interest include GC; report of genotype data of individual genetic variants in (or methylation status of) CDH1 in participants with and without GC (or providing odds ratios [OR] and their variances).Study appraisal and synthesis methods included the use of OR as a measure of the association, calculated from random effects models in meta-analyses. We used I for the assessment of between-study heterogeneity, and publication bias was assessed using funnel plot and Egger test.A total of 33 studies from 30 published articles met the eligibility criteria and were included in our analyses. We found no association between C-160A and GC (OR = 0.88; 95% confidence interval [CI], 0.71-1.08; P = 0.215), assuming an additive model (reference allele C). C-160A was associated with cardia (OR = 0.21; 95% CI, 0.11-0.41; P = 2.60 × 10), intestinal (OR = 0.66; 95% CI, 0.49-0.90; P = 0.008), and diffuse GC (OR = 0.57; 95% CI, 0.40-0.82; P = 0.002). The association of C-160A with noncardia GC is of bottom line significance (OR = 0.65; 95% CI, 0.42-1.01; P = 0.054). Multiple other less-studied genetic variants in CDH1 also exhibited association with GC. Gene-based analysis indicated a significant cumulative association of genetic variants in CDH1 with GC (all Ps <10). Sensitivity analysis excluding studies not meeting Hardy-Weinberg equilibrium (HWE) yielded similar results. Analysis by ethnic groups revealed significant association of C-160A with cardia GC in both Asian and whites, significant association with noncardia GC only in Asians, and no significant association with intestinal GC in both ethnic groups. There was significant association of C160-A with diffuse GC in Asians (P = 0.011) but not in whites (P = 0.081). However, after excluding studies that violate HWE, this observed association is no longer significant (P = 0.126). We observed strong association of promoter hypermethylation of CDH1 with GC (OR = 12.23; 95% CI, 8.80-17.00; P = 1.42 × 10), suggesting that epigenetic regulation of CDH1 could play a critical role in the etiology of GC.Limitations of this study are as follows: we could not adjust for confounding factors; some meta-analyses were based on a small number of studies; sensitivity analysis was limited due to unavailability of data; we could not test publication bias for some meta-analyses due to small number of included studies.We found no significant association of the widely studied genetic variant C-160A, but identified some other genetic variants showing significant association with GC. Future studies with large sample sizes that control for confounding risk factors and/or intensively interrogate CpG sites in CDH1 are needed to validate the results found in this study and to explore additional epigenetic loci that affect GC risk.

Effect of breastfeeding on childhood BMI and obesity: the China Family Panel Studies.

The objective of this study is to investigate the effect of breastfeeding on childhood obesity in China.We used data collected from the China Family Panel Studies, an ongoing, prospective, and nationwide longitudinal study to explore the extensive and dynamic social changes in China. A total of 7967 children were included in the analysis. Duration of breastfeeding was first treated as a continuous variable and subsequently dichotomized into ever versus never, ≥6 months versus <6 months, ≥8 months versus < 8 months, and ≥12 months versus <12 months. Multiple imputation was conducted and regressions with propensity score matching were performed. We also performed quantile regression to examine whether breastfeeding has an effect on childhood obesity among children with a specific quantile of body mass index (BMI).Consistent with findings from recent studies, in both adjusted and adjusted regressions, we did not find any statistically significant effect of breastfeeding on reducing the risk of obesity (unadjusted odds ratio, OR = 1.02, 95% confidence interval, CI 0.99, 1.05, P = 0.12; adjusted OR 1.01, 95% CI 0.98, 1.05, P = 0.36) or excessive weight (unadjusted OR = 1.01, 95% CI 0.99, 1.03, P = 0.26; adjusted OR = 1.00, 95% CI 0.98, 1.02, P = 0.90). Results were similar using various dichotomization of duration of breastfeeding. Quantile regression revealed that longer duration of breastfeeding is associated with higher BMI among children with small to medium quantile of BMI.Our findings echo recent research and caution against any population-wide strategy in attempting to reduce overweight and obesity through promotion of breastfeeding.

17Beta-estradiol differentially protects cortical pericontusional zone from programmed cell death after traumatic cerebral contusion at distinct stages via non-genomic and genomic pathways.

Pericontusional zone (PCZ) of traumatic cerebral contusion is a target of pharmacological intervention. Our previous study indicated that 17beta-estradiol has a protective role in PCZ after traumatic cerebral contusion via the upregulation of estrogen receptor (ER) alpha mRNA induction and protein expression as well as inhibition of caspase-3 activation, suggesting that genomic signaling pathway is implicated in the protective effect of 17beta-estrodiol. Recent findings demonstrated that 17beta-estradiol also acts on the extranuclear/membrane ER to activate non-genomic signaling pathway to regulate cellular functions and exert the protective effect in the brain. It is still unclear how and whether genomic and non-genomic pathways of 17beta-estradiol are involved in the neuroprotection in PCZ. Our current study demonstrates that 17beta-estradiol activates ERK1/2 and Akt at the early stage and induces ERalpha and survivin mRNA at the late stage to modulate its protection via the suppression of caspase-3 activation in PCZ. These findings suggest that 17beta-estrodiol differentially plays its protective roles via genomic and non-genomic signaling pathways in PCZ after traumatic cerebral contusion.

17beta-estradiol attenuates programmed cell death in cortical pericontusional zone following traumatic brain injury via upregulation of ERalpha and inhibition of caspase-3 activation.

Pericontusional zone (PCZ) of traumatic cerebral contusion is a target of pharmacological intervention. It is well studied that 17beta-estradiol has a protective role in ischemic brain injury, but its role in brain protection of traumatic brain damage deserves further investigation, especially in pericontusional zone. Here we show that 17beta-estradiol enhances the protein expression and mRNA induction of estrogen alpha receptor (ERalpha) and prevents from programmed cell death in cortical pericontusional zone. ERalpha specific antagonist blocks this protective effect of 17beta-estradiol. Caspase-3 activation occurs in cortical pericontusional zone of the oil-treated injured rat brain and its activation is inhibited by 17beta-estradiol treatment. Additionally, ERalpha specific antagonist reverses this inhibition. Pan-caspase inhibitor also protect cortical pericontusional zone from programmed cell death. Our present study indicates 17beta-estradiol protects from programmed cell death in cortical pericontusional zone via enhancement of ERalpha and decrease of caspase-3 activation.