The clinical trajectory of peripheral blood immune cell subsets, T-cell activation, and cytokines in septic patients.

OBJECTIVE AND DESIGN: Changes in the immune status of patients with sepsis may have a major impact on their prognosis. Our research focused on changes in various immune cell subsets and T-cell activation during the progression of sepsis. METHODS AND SUBJECTS: We collected data from 188 sepsis patients at the First Affiliated Hospital of Zhejiang University School of Medicine. The main focus was on the patient's immunocyte subset typing, T-cell activation/Treg cell analysis, and cytokine assay, which can indicate the immune status of the patient. RESULTS: The study found that the number of CD4+ T cells, CD8+ T cells, NK cells, and B cells decreased early in the disease, and the decrease in CD4+ and CD8+ T cells was more pronounced in the death group. T lymphocyte activation was inhibited, and the number of Treg cells increased as the disease progressed. T lymphocyte inhibition was more significant in the death group, and the increase in IL-10 was more significant in the death group. Finally, we used patients' baseline conditions and immunological detection indicators for modeling and found that IL-10, CD4+ Treg cells, CD3+HLA-DR+ T cells, and CD3+CD69+ T cells could predict patients' prognosis well. CONCLUSION: Our study found that immunosuppression occurs in patients early in sepsis. Early monitoring of the patient's immune status may provide a timely warning of the disease.

Gastrodia elata and parishin ameliorate aging induced 'leaky gut' in mice: Correlation with gut microbiota.

BACKGROUND: The aging-induced decrease in intestinal barrier function contributes to many age-related diseases. Studies on preventive measures for "leaky gut" may help improve the quality of life of geriatric patients. The potent anti-aging effect of Gastrodia elata and parishin, which is one of its active ingredients, has been reported previously. However, their effects on the gut remain elusive, and the effect of parishin on mammals has not been studied. METHODS: We used quantitative RT-PCR, western blotting, immunohistochemical analysis, and 16S rRNA sequencing to investigate the effect of G. elata and parishin on the intestinal barrier function of D-Gal-induced aging mice. RESULTS: G. elata and parishin prevented the decrease in tight junction protein (TJP) expression and morphological changes, modulated the composition of fecal microbiota to a healthier state, and reversed the translocation of microbial toxins and systemic inflammation. The correlation analyses showed that TJP expression and systemic inflammation were significantly positively or negatively correlated with the composition of fecal microbiota after G. elata and parishin administration. Additionally, TJP expression was also correlated with systemic inflammation. Moreover, G. elata and parishin administration reversed the decreased or increased expression of aging-related biomarkers, such as FOXO3a, SIRT1, CASPASE3 and P21, in the gut. CONCLUSIONS: These results suggested that G. elata and parishin could prevent gut aging and ameliorate the "leaky gut" of aged mice and that the underlying mechanism is related to the mutual correlations among barrier function, fecal microbiota composition, and inflammation.

Immunosenescence: A Critical Factor Associated With Organ Injury After Sepsis.

Progressive immune dysfunction associated with aging is known as immunosenescence. The age-related deterioration of immune function is accompanied by chronic inflammation and microenvironment changes. Immunosenescence can affect both innate and acquired immunity. Sepsis is a systemic inflammatory response that affects parenchymal organs, such as the respiratory system, cardiovascular system, liver, urinary system, and central nervous system, according to the sequential organ failure assessment (SOFA). The initial immune response is characterized by an excess release of inflammatory factors, followed by persistent immune paralysis. Moreover, immunosenescence was found to complement the severity of the immune disorder following sepsis. Furthermore, the immune characteristics associated with sepsis include lymphocytopenia, thymus degeneration, and immunosuppressive cell proliferation, which are very similar to the characteristics of immunosenescence. Therefore, an in-depth understanding of immunosenescence after sepsis and its subsequent effects on the organs may contribute to the development of promising therapeutic strategies. This paper focuses on the characteristics of immunosenescence after sepsis and rigorously analyzes the possible underlying mechanism of action. Based on several recent studies, we summarized the relationship between immunosenescence and sepsis-related organs. We believe that the association between immunosenescence and parenchymal organs might be able to explain the delayed consequences associated with sepsis.

A Combination of Serum Biomarkers in Elderly Patients with Sarcopenia: A Cross-Sectional Observational Study.

BACKGROUND: The pathogenesis of sarcopenia in the elderly has not yet been fully understood. This study aimed to explore the relationship between sarcopenia and several serum biomarkers in elderly population. METHODS: It was an observational cross-sectional study of data collected from 70 patients. According to the criteria of the Asian Working Group for Sarcopenia (AWGS), subjects were divided into the sarcopenia group and nonsarcopenic group. We compared age, body mass index (BMI), biochemical indexes, smoking status, underlying disease, muscle mass, handgrip strength (HS), gait speed (GS), skinfold thickness, muscle thickness, and IL-6, IL-10, IL-17A, and TNF-α levels between these groups. RESULTS: Of the 70 subjects, 35 patients were diagnosed with sarcopenia. The number of men was higher than that of women in both groups. The patients with sarcopenia were older and had lower BMI and muscle thickness but higher SARC-F questionnaire scores. However, the difference in smoking status and skinfold thickness between these two groups were not statistically significant. Higher IL-6, IL-17A, and TNF-α levels were observed in participants with sarcopenia (P < 0.05). Patients with sarcopenia had a lower IL-10 level. Positive associations were present between the severity of sarcopenia and IL-6, IL-17A, and TNF-α levels, while there was an inverse correlation between the presence of sarcopenia and IL-10 level. CONCLUSIONS: Our research found that in sarcopenic elderly subjects, the serum levels of several biomarkers, such as IL-6, IL-17A, and TNF-α, were higher than those in nonsarcopenic elderly persons. Further studies are needed to explore the possible molecular mechanisms and discover new therapeutic targets.

Paraneoplastic myelitis associated with durvalumab treatment for extensive-stage small cell lung cancer.

Paraneoplastic neurologic syndromes(PNSs) caused by immune checkpoint inhibitors(ICIs) is rare and requires clinicians to differentiate between disease progression and immune-related adverse effects(irAEs). We hereby report the case of immune-related myelitis accompanied by positive paraneoplastic autoantibodies following durvalumab treatment for extensive-stage small cell lung cancer (ES-SCLC). A 70-year-old Chinese woman with ES-SCLC was administered durvalumab with etoposid-platinum(EP) as first-line treatment. Four cycles after treatment with EP plus ICI, she developed immune-related myelitis with positive paraneoplastic autoantibodies (CV2, SOX1, ZIC4). Spinal MRI showed diffuse abnormal signal shadow in the cervicothoracic spinal cord. She was discontinued for chemotherapy, and treated with high-dose steroids, intravenous immunoglobulin and plasmapheresis, maintenance therapy with steroids resulted in a favorable neurologic outcome. This is the first report of durvalumab-related PNSs. We supposed that the development of paraneoplastic myelitis was causally related to immune activation by durvalumab. Prompt diagnosis and therapeutic intervention are essential for the effective treatment of paraneoplastic myelitis.

Gut microbiota signatures in Schistosoma japonicum infection-induced liver cirrhosis patients: a case-control study.

BACKGROUND: Several studies have assessed the role of gut microbiota in various cirrhosis etiologies, however, none has done so in the context of Schistosoma japonicum infection in humans. We, therefore, sought to determine whether gut microbiota is associated with S. japonicum infection-induced liver cirrhosis. METHODS: From December 2017 to November 2019, 24 patients with S. japonicum infection-induced liver cirrhosis, as well as 25 age- and sex-matched controls from the Zhejiang Province, China, were enrolled. Fecal samples were collected and used for 16S rRNA gene sequencing (particularly, the hypervariable V4 region) using the Illumina MiSeq system. Wilcoxon Rank-Sum and PERMANOVA tests were used for analysis. RESULTS: Eight hundred and seven operational taxonomic units (OTUs) were detected, of which, 491 were common between the two groups, whereas 123 and 193 were unique to the control and cirrhosis groups, respectively. Observed species, Chao, ACE, Shannon, Simpson, and Good's coverage indexes, used for alpha diversity analysis, showed values of 173.4 ± 63.8, 197.7 ± 73.0, 196.3 ± 68.9, 2.96 ± 0.57, 0.13 ± 0.09, and 1.00 ± 0.00, respectively, in the control group and 154.0 ± 68.1, 178.6 ± 75.1, 179.9 ± 72.4, 2.68 ± 0.76, 0.19 ± 0.18, and 1.00 ± 0.00, respectively, in the cirrhosis group, with no significant differences observed between the groups. Beta diversity was evaluated by weighted UniFrac distances, with values of 0.40 ± 0.13 and 0.40 ± 0.11 in the control and cirrhosis groups, respectively (P > 0.05). PCA data also confirmed this similarity (P > 0.05). Meanwhile, the relative abundance of species belonging to the Bacilli class was higher in cirrhosis patients [median: 2.74%, interquartile range (IQR): 0.18-7.81%] than healthy individuals (median: 0.15%, IQR: 0.47-0.73%; P < 0.01), and that of Lactobacillales order was also higher in cirrhosis patients (median: 2.73%, IQR: 0.16-7.80%) than in healthy individuals (median: 0.12%, IQR: 0.03-0.70%; P < 0.05). CONCLUSIONS: Cumulatively, our results suggest that the gut microbiota of S. japonicum infection-induced liver cirrhosis patients is similar to that of healthy individuals, indicating that bacterial taxa cannot be used as non-invasive biomarkers for S. japonicum infection-induced liver cirrhosis.

Sarcopenia is associated with the presence of nonalcoholic fatty liver disease in Zhejiang Province, China: a cross-sectional observational study.

BACKGROUND: Currently, both non-alcoholic fatty liver disease (NAFLD) and sarcopenia have attracted extensive attention in public health. However, the relationship between NAFLD and sarcopenia remains unclear. This study aimed to clarify the sex-specific association between sarcopenia and NAFLD according to the Asian Working Group for Sarcopenia (AWGS). METHODS: Dual-energy X-ray absorptiometry (DXA) and hepatic ultrasonography were measured in 578 participants (92 men and 486 women) during their annual health examinations. Multivariate logistic regression models were used to explore the association between NAFLD and sarcopenia with its two components. RESULTS: A total of 154 participants (30 men and 124 women) had NAFLD. The prevalence of sarcopenia was higher among the participants with NAFLD than among those without NAFLD (men: 20.0% vs. 9.7%, P = 0.295, women: 15.3% vs. 8.0%, P = 0.019). Low muscle mass (LMM) was independently associated with NAFLD in both men and women (men: odds ratio [OR], 2.88; 95% confidence interval [CI] 1.52-5.46; women: OR, 2.08; 95% CI 1.63-2.67). However, low muscle strength (LMS) was independently associated with NAFLD only in male participants, with an OR of 1.15 (95% CI 1.02-1.28). CONCLUSION: The occurrence of sarcopenia was associated with a higher risk of NAFLD, especially in men, as demonstrated by lower muscle mass and lower muscle strength.

TLR3 inhibitor and tyrosine kinase inhibitor attenuate cigarette smoke/poly I:C-induced airway inflammation and remodeling by the EGFR/TLR3/MAPK signaling pathway.

Tobacco smoke is the major risk factor for developing chronic obstructive pulmonary disease (COPD). Viral infection is a major cause of COPD exacerbation, which lacks effective drug treatments. In the present study, to mimic the pathogenesis of COPD, we employed a TLR3 ligand [Poly (I:C), PIC] to mimic viral infection to determine whether it enhances the effects of cigarette smoke (CS)-induced airway inflammation and remodeling. Our results showed that PIC enhanced the effects of cigarette smoke extract (CSE)-induced inflammatory cytokine IL-1ß, TNF-α and IL-8 mRNA expression and remodeling factor E-cadherin, α-SMA and TGF-ß1 mRNA expression with TLR3 upregulation and EGFR phosphorylation in pulmonary epithelial NCI-H292 cells. These responses were inhibited by a TLR3/dsRNA complex inhibitor (TLR3i) or a tyrosine kinase inhibitor icotinib (Ico). Similarly, in the PIC-enhanced CS-induced airway inflammation and remodeling mouse model, treatment with TLR3i or Ico reduced the mRNA and protein expression of the inflammatory cytokines IL-1ß and TNF-α and keratinocyte chemoattractant (KC) and the remodeling factors α-SMA, TGF-ß1, MMP-9 and MUC5AC, while increasing E-cadherin mRNA and protein expression. Furthermore, we found that TLRi and Ico can attenuate the airway hyperreactivity induced by PIC, which is enhanced by CS. Finally, PIC enhanced the effects of CS on TLR3 upregulation and EGFR phosphorylation and significantly increased Erk1/2 and P38 phosphorylation, whereas TLR3i and Ico markedly suppressed TLR3 upregulation and EGFR, Erk1/2 and P38 phosphorylation in the model. Our findings suggest that TLR3/EGFR may be a potential target for the treatment of airway inflammation and remodeling in COPD.

Multidisciplinary treatment of a patient with necrotizing fasciitis caused by Staphylococcus aureus: A case report.

BACKGROUND: Necrotizing fasciitis is a severe bacterial skin infection that spreads quickly and is characterized by extensive necrosis of the deep and superficial fascia resulting in the devascularization and necrosis of associated tissues. Because of high morbidity and mortality, accurate diagnosis and early treatment with adequate antibiotics and surgical intervention are vital. And timely identification and treatment of complications are necessary to improve survival of patient. CASE SUMMARY: We report a case of necrotizing fasciitis caused by Staphylococcus aureus in a patient using high doses of glucocorticoid and suffering from secondary diabetes mellitus. He was admitted to our hospital due to redness and oedema of the lower limbs. After admission, necrotizing fasciitis caused by Staphylococcus aureus was considered, and he was discharged after B-ultrasound drainage and multiple surgical operations. In the process of treatment, multiple organ functions were damaged, but with the help of multi-disciplinary treatment, the patient got better finally. CONCLUSION: The key to successful management of necrotizing fasciitis is an early and accurate diagnosis. The method of using vacuum sealing drainage in postoperative patients can keep the wound dry and clean, reduce infection rate, and promote wound healing. Interdisciplinary collaboration is a vital prerequisite for successful treatment.

Multiorgan Drug Action of Levosimendan in Critical Illnesses.

Cardiotonic drugs mainly include digitalis, catecholamines, phosphodiesterase inhibitors, and calcium sensitizers, which have been successively discovered and applied in clinical practice. However, there are only a few new drugs available in this field, and the selection is very limited. Digitalis, catecholamines, and phosphodiesterase inhibitors increase myocardial contractility by increasing intracellular concentrations of cyclic adenosine monophosphate (cAMP) and Ca2+, and this increase in intracellular calcium ion concentration enhances myocardial oxygen consumption and causes arrhythmia. For these reasons, the research focus on positive inotropic agents has shifted from calcium mobilization to calcium sensitization. Intracellular calcium sensitizers are more effective and safer drugs because they do not increase the intracellular concentration of calcium ions. However, only three calcium sensitizers have been fully developed and used in the past three decades. One of these drugs, levosimendan, has multiple molecular targets and exerts its pharmacological effects by not only increasing myocardial contractility, but also enhancing respiratory muscle function and liver and kidney protection, and it is useful for patients with severe sepsis and septic shock. Recently, more than 60 randomized controlled clinical trials of levosimendan have been reported; however, these clinical trials have occasionally shown different findings. This article reviews the research progress of levosimendan in critical illnesses in recent years.

VEGF levels in plasma in relation to metabolic control, inflammation, and microvascular complications in type-2 diabetes: A cohort study.

The vascular endothelial growth factor (VEGF) level in human circulation may reflect the severity of endothelial dysfunction in patients with diabetes mellitus, which leads to diabetic microvascular complications.We determined plasma VEGF levels as well as metabolic control and inflammatory factors in 26 healthy subjects and 52 type-2 diabetes mellitus (T2DM) patients with or without diabetic microvascular complications. Pearson correlation coefficient was used to evaluate the associations among those indices.The results showed that VEGF levels in plasma were positively correlated with fasting blood glucose level, glycosylated hemoglobin (HbA1c) level, type 1 helper T cell (Th1) percentage, and Th1/Th2 ratio, while they were negatively correlated with regulatory T cell percentage. Multiple linear regression analysis showed that HbA1c and Th1/Th2 ratio were the independent predictors of VEGF levels in T2DM patients.Thus, in T2DM patients with poor glycemic control as well as an elevated Th1/Th2 cell ratio, more VEGF might be released.

Characteristics of hyperuricemia in older adults in China and possible associations with sarcopenia.

OBJECTIVE: This cross-sectional study aimed to investigate the characteristics and epidemiology of hyperuricemia in older adults in China and evaluate possible associations between hyperuricemia and sarcopenia. METHODS: Three hundred and eighty-eight study subjects (>60 years old) meeting the inclusion criteria received blood tests and standardized examinations for bone mineral density, muscle mass, muscle strength, and physical performance. Data including demographic and clinical characteristic and comorbidity were also collected. All data were analyzed retrospectively. RESULTS: In the study population, higher uric acid levels were significantly correlated with higher muscle mass, grip strength, and bone density, but were unrelated to physical performance. When uric acid levels were separated into quartiles and the population was divided by sex, the correlation of uric acid to muscle mass was retained in some quartiles for both men and women, and the correlation to handgrip was only retained for one quartile for men. The correlation to bone density was retained in women in all analyses. CONCLUSION: In the population as a whole, higher uric acid levels were significantly correlated with higher muscle mass, grip strength, and bone density, but had no relationship to physical performance. Differences between men and women in these relationships need to be studied further.

Early Diagnostic Performance of Heart-Type Fatty Acid Binding Protein in Suspected Acute Myocardial Infarction: Evidence From a Meta-Analysis of Contemporary Studies.

BACKGROUND: Although cardiac troponin is the cornerstone in diagnosis of acute myocardial infarction (AMI), the accuracy is still suboptimal in the early hours after chest pain onset. Due to its small size, heart-type fatty acid-binding protein (H-FABP) has been reported accurate in diagnosis of AMI, however, this remains undetermined. The aim is to investigate the diagnostic performance of H-FABP alone and in conjunction with high-sensitivity troponin (hs-Tn) within 6 hours of symptom onset. Furthermore, accuracy in 0h/3h algorithm was also assessed. METHODS: Medline and EMBASE databases were searched; sensitivity, specificity and area under ROC curve (AUC) were used as measures of the diagnostic accuracy. We pooled data on bivariate modelling, threshold effect and publication bias was applied for heterogeneity analysis. RESULTS: Twenty-two studies with 6602 populations were included, pooled sensitivity, specificity and AUC of H-FABP were 0.75 (0.68-0.81), 0.81 (0.75-0.86) and 0.85 (0.82-0.88) within 6 hours. Similar sensitivity (0.76, 0.69-0.82), specificity (0.80, 0.71-0.87) and AUC (0.85, 0.82-0.88) of H-FABP were observed in 4185 (63%) patients in 0h/3h algorithm. The additional use of H-FABP improved the sensitivity of hs-Tn alone but worsened its specificity (all p<0.001), and resulted in no improvement of AUC (p>0.99). There was no threshold effect (p=0.18) and publication bias (p=0.31) in this study. CONCLUSIONS: H-FABP has modest accuracy for early diagnosis of AMI within 3 and 6 hours of symptom onset. The incremental value of H-FABP seemed much smaller and was of uncertain clinical significance in addition to hs-Tn in patients with suspected AMI. Routine use of H-FABP in early presentation does not seem warranted.

Association between the vascular endothelial growth factor single nucleotide polymorphisms and diabetic retinopathy risk: A meta-analysis.

BACKGROUND: The aim of the present study was to reveal the relationship between vascular endothelial growth factor (VEGF) single nucleotide polymorphisms (SNPs) and susceptibility to diabetic retinopathy (DR). METHODS: A literature review was conducted (PubMed, Web of Science, Embase) to identify papers about VEGF SNPs and DR published up to 23 September 2015. The VEGF gene SNPs analyzed with regard to DR susceptibility were rs2010963 (G > C), rs833061 (T > C), rs699947 (C > A), rs3025039 (C > T) and rs1570360 (G > A). Pooled odds ratios (OR) and 95% confidence intervals (CI) were calculated, and meta-analyses were performed using fixed or random effects models. RESULTS: Sixteen studies were included in the meta-analysis. Significant associations between the rs3025039 (C > T) polymorphism and increased DR risk were found in the allele model (T/C; pooled OR 1.60, 95% CI 1.07-2.41, P = 0.02), homozygote model (TT/CC; pooled OR 2.08, 95% CI 1.29-3.35, P = 0.003), heterozygote model (TC/CC; pooled OR 1.68, 95% CI 1.04-2.72, P = 0.04), dominant model (TT+TC/CC; pooled OR 1.72, 95% CI 1.06-2.80, P = 0.03), and recessive model (TT/TC+CC; pooled OR 1.80, 95% CI 1.12-2.90, P = 0.02). For rs833061, a significant association between VEGF SNPs and DR was found only in the allele model (C/T; pooled OR 6.34, 95% CI 2.10-19.14, P = 0.001). CONCLUSIONS: The rs3025039 and rs833061 SNPs are most likely associated with an increased risk of DR. The T allele in rs3025039 and the C allele in rs833061 are associated with increased DR susceptibility.

Clinical Outcomes of Coronary Artery Bypass Grafting vs Percutaneous Coronary Intervention in Octogenarians With Coronary Artery Disease.

BACKGROUND: The number of elderly people receiving treatment for coronary artery disease (CAD) is increasing, and there are few studies that compared the outcomes of coronary artery bypass grafting (CABG) and percutaneous coronary intervention (PCI) in the elderly. The objective of this study was to compare outcomes of CABG and PCI in octogenarians with CAD. METHODS: We conducted a search to identify articles that reported the results of 2-arm studies that compared CABG with PCI in octogenarians. The primary outcomes were short-term mortality and overall survival, and secondary outcomes included length of hospital stay and cerebrovascular accident (CVA) and myocardial infarction (MI) rates. RESULTS: Seven studies that enrolled 1879 patients who received CABG and 1432 treated with PCI were included. Short-term mortality was significantly less for patients in the PCI arms (odds ratio [OR], 1.47; 95% confidence interval [CI], 1.05-2.06; P = 0.02), as was duration of hospital stay (difference in means, 6.07; 95% CI, 2.81-9.34; P < 0.001). Patients in the CABG arms had longer overall survival (hazard ratio, 0.81; 95% CI, 0.73-0.89; P < 0.001). CVA and MI rates were similar (CVA: OR, 1.06; 95% CI, 0.57-1.95; P = 0.86; MI: OR, 0.70; 95% CI, 0.42-1.17; P = 0.17). CONCLUSIONS: The results suggest that physicians should consider not only the clinical features of CAD, but also the elderly patients future health outlook when choosing a revascularization procedure.

The Efficacy of Ginseng-Related Therapies in Type 2 Diabetes Mellitus: An Updated Systematic Review and Meta-analysis.

Few randomized clinical trials have evaluated the efficacy of ginseng in patients with type 2 diabetes mellitus (T2DM). The current meta-analysis evaluated the ginseng-induced improvement in glucose control and insulin sensitivity in patients with type-2 diabetes or impaired glucose tolerance.Randomized clinical trials comparing ginseng supplementation versus control, in patients with T2DM or impaired glucose tolerance, were hand-searched from Medline, Cochrane, and Google Scholar databases by 2 independent reviewers using the terms "type 2 diabetes/diabetes/diabetic, impaired glucose tolerance, and ginseng/ginsenoside(s)." The primary outcome analyzed was the change in HbA1c, whereas the secondary outcomes included fasting glucose, postprandial glucose, fasting insulin, postprandial insulin, insulin resistance Homeostatic Model Assessment of Insulin Resistance (HOMA-IR), triglycerides, total cholesterol, low density lipoprotein (LDL), and high density lipoprotein (HDL).Of the 141 studies identified, 8 studies were chosen for the current meta-analysis. The average number of patients, age, and sex distribution among the groups were comparable. Results reveal no significant difference in HbA1c levels between the ginseng supplementation and the control groups (pooled standardized difference in means = -0.148, 95% CI: -0.637 to 0.228, P = 0.355). Ginseng supplementation improved fasting glucose, postprandial insulin, and HOMA-IR levels, though no difference in postprandial glucose or fasting insulin was observed among the groups. Similarly, triglycerides, total cholesterol, and LDL levels showed significant difference between the treatment groups, while no difference in HDL was seen. In addition, ginseng-related therapy was ineffective in decreasing the fasting glucose levels in patients treated with oral hypoglycemic agents or insulin.The present results establish the benefit of ginseng supplementation in improving glucose control and insulin sensitivity in patients with T2DM or impaired glucose intolerance.

Efficacy and Safety of Denosumab in Postmenopausal Women With Osteoporosis: A Meta-Analysis.

The purpose of this study was to perform a meta-analysis to examine the efficacy and safety of denosumab in postmenopausal women with osteoporosis.Medline, Cochrane Library, EMBASE, and Google Scholar databases were searched until October 30, 2014 using combinations of the following search terms: osteoporosis, postmenopause, postmenopausal, women, denosumab. The primary outcome was bone mineral density (BMD) change, and secondary outcomes were change in the bone turnover markers ß-isomerized carboxy-terminal cross-linking telopeptide of type I collagen (CTX) and serum procollagen type I amino-terminal propeptide (P1NP), and adverse events.Patients treated with denosumab had significantly increased BMD of the lumbar spine (7.58%), total hip (4.86%), and distal third of the radius (2.92%) than those treated with placebo (all, P < 0.001). Patients treated with denosumab had a significant decrease of CTX (-66.16%) and P1NP (-64.65%) as compared with those treated with placebo (both, P < 0.001). Adverse events were similar between the 2 groups (pooled odds ratio = 1.04, P = 0.625).Denosumab increases BMD and decreases markers of bone turnover in postmenopausal women with osteoporosis, and is not associated with significant side-effects.

Apple Polyphenols Decrease Atherosclerosis and Hepatic Steatosis in ApoE-/- Mice through the ROS/MAPK/NF-κB Pathway.

In this study, we examined the effects of apple polyphenols (APs) on hyperlipidemia, atherosclerosis, hepatic steatosis and endothelial function and investigated the potential mechanisms. ApoE(-/-) mice were fed a western-type diet and orally treated with APs (100 mg/kg) or atorvastatin (10 mg/kg) for 12 weeks. Hyperlipidemia and atherosclerosis in the aortic sinuses and, and hepatic lipidosis were measured. The treatment with APs or atorvastatin induced a remarkable reduction in the atherosclerotic lesions and hepatic steatosis and decreased the levels of low-density lipoprotein, triglyceride, CCL-2 and VCAM-1 levels in the plasma. Conversely, the APs significantly increased the plasma levels of high-density lipoprotein (HDL) cholesterol and markedly up-regulated the glutathione peroxidase (GPx), catalase (CAT) and superoxide dismutase (SOD) levels in liver tissues. Moreover, the APs treatment modulated lipid metabolism by up-regulating the transcription of associated hepatic genes including PPARα, while down-regulating the transcription of SCAP and its downstream genes associated with lipid synthesis in the liver. Histological assessment showed that the APs treatment also reduced the macrophage infiltration in the aortic root plaque and the inflammatory cells infiltrations to the liver tissues. Moreover, we confirmed that the APs treatment greatly reduced the ox-LDL-induced endothelial dysfunction and monocyte adhesion to rat aortic endothelial cells (RAECs). Mechanistically, the APs treatment suppressed the ROS/MAPK/NF-κB signaling pathway, and consequently, reduced CCL-2, ICAM-1 and VCAM-1 expression. Our results suggest that the APs are a beneficial nutritional supplement for the attenuation of atherosclerosis.