Study group (n = 6) were received streptozotocin (50 mg/kg) and control group (n = 6) physiologic saline. The blood glucose and ketonuria were measured, and necropsy was performed on them on third, fourth, and fifth days. Immunohistochemistry revealed that marked increase in caspase-3 reaction pancreas, liver, and kidney in the study group than control group. COX-1 slightly increased in these organs in study group compared to controls. Immunohistochemically COX-2 reaction was markedly positive in liver and kidney, but slightly increased in pancreas. The most increased reaction was observed in CRS and all organs were markedly positive. HIF-1α expression was also increased but the reaction was more severe in pancreas than liver and kidney. This study indicated that degeneration starts in organs in early stages of the disease and the most effective route for degeneration related to increase of calcium influx and hypoxia upon cells in DM.Liver and kidney commonly affected by diabetes in chronic cases but pathogenetic mechanisms are not fully understood in early stages of the disease. The aim of this study was to investigate the immunohistochemical expression of caspase-3, cyclooxygenase (COX)-1 and-2, calcium sensing receptor (CSR), and hypoxia inducible factor-1 Diabetes mellitus is a metabolic disorder that results from a reduction of insulin available for normal function of many cells in the body. In some cases, increased concentrations of glucagon contribute to development of persistent hyperglycemia. In addition to chronic hyperglycemia, DM is characterized by disturbance of carbohydrate, fat, and protein metabolism resulting from defects in insulin secretion, insulin action, or both. The diseases can also be recognized during less overt stages, most usually by the presence of glucose intolerance. The effects of DM include long-term damage, dysfunction, and failure of various organs, especially the eyes, kidneys, livers, hearts, and blood vessels .2+ triggers exocytosis of the insulin granules is obtained from experiments using β cell of which the plasma membrane is permeabilized in these cells, the membrane potential is dissipate and the cytosolic concentration of small molecules can be controlled [α has central role in degeneration and a transcriptional activator that promotes angiogenesis [α expression is also induced under normoxic conditions when cells are stimulated with growth factors, inflammatory cytokines, lactate, or prostaglandins [In the pathogenesis of DM, several factors are responsible for the decreased availability of insulin. Hyperglycemia, and its attendant effects upon cells, underlies the pathogenic lesions of DM . Cellulantrolled . Calciumntrolled –10. Hypoogenesis , 12. HIFglandins –15.DM is a complex disease and causes numerous cellular damages in different organs. A number of pathogenetic advances have been made during the past decade but numerous mechanisms need to be clarified. The pathogenetic mechanisms are likely interactive and linked in DM. For that reason, mechanism of cellular damage is not fully understood. This preliminary study was designed to explore the cellular distribution and the underlying mechanisms of hypoxia and calcium influx in experimental diabetes.μm thickness. Tissue sections were stained with hematoxylin-eosin (HE) and examined microscopically. Afterward, pancreas, liver, and kidney samples were immunostained with caspase-3 , COX-1 , COX-2 , CSR , and HIF-1α  according to the manufactures' instructions. In this study, avidin-biotin complex peroxidase (ABC-P) method was used for immunohistochemistry. Paraffin blocks were sectioned at 5 μm for immunohistochemical examination, and sections were attached to glass slides coated with poly-L-lysine. The slides were dried overnight at 37°C to optimize adhesion. Sections were deparaffinized through xylene, and tissues were rehydrated in sequentially graduated ethyl alcohol. Slides were incubated in hydrogen peroxide in methanol for 10 min to reduce nonspecific background staining due to endogenous peroxidase. The sections were washed twice, in phosphate buffer solution (PBS). Then, tissues were boiled in 1 : 100 citrate buffer solution for10 min and cooled for 20 min. The cooled tissues were washed four times in PBS prior to application of blocking serum for 5 min. Then, primary antibody was applied; tissues were incubated for 30 min at room temperature. They were rinsed 4 times in PBS, given an application of biotinylated anti-polyvalent antibody and incubated for 10 min at room temperature. After being washed three times in PBS, streptavidin peroxidase was applied and the samples were incubated for 10 min at room temperature, and then rinsed 4 times in PBS. Tissues were further incubated for 20 min at room temperature in a solution of DAB  chromogen. After being washed in PBS, tissues were counter stained with Mayer's haematoxylin, washed in water, and coverslips were applied with mounting media. For negative control, primary antibody was not added to the sections.Twelve female Sprague-Dawley rats, weighing 125 to 150 g and aged 2 months, were maintained at the Experimental Animal Housing Unit of the University of Akdeniz. They were randomly allocated into 2 groups, as follows: study group that treated with STZ and control group. Both groups were composed of 6 rats and were allowed free access to water and food. Rats were fasted before the STZ injection. A single intraperitoneal injection of 50 mg/kg STZ  dissolved immediately before administration in freshly prepared 50 mmol/L citrate buffer (pH 4.0) that was given on day 0. Control animals received an equivalent volume of physiologic saline. Urine samples were collected at 3rd, 4th, and 5th days. At the third day, two rats form, study group and two rats from the control group were anesthetized with ether before blood and tissue samples were obtained. The blood glucose concentration was measured in blood from jugular vein in the morning from 2 rats in each group before euthanasia, and then necropsy was performed on them after the third day. The MS9 blood counting equipment was used for hematological analysis of the blood drawn in EDTA tubes. Glucose levels were analyzed in serum samples using IDEXX VetTest equipment and reagents. Pancreas, liver, and kidney tissue samples were collected and fixed in 10% buffered formalin. After routine procedure, tissues were blocked in paraffin and cut to 5 In order to evaluate the percentage of immunopositive cells, 100 cells calculated in 10 different microscopic high-powered fields of each slide were examined under the 40x objective of a trinocular microscope (Nikon E600) and microphotography apparatus. The count of positive cells one high-power field for each marker was noted and compared with control groups.t test was used. Calculations were made using the SPSS 13.0 program pack. P < 0.05 was accepted as statistically significant.In the statistical evaluations, Students α immunostained sections revealed severe damage in these organs in early stages of the DM. Statistical results of immunohistochemical observation were shown in graphic. Caspase-3 immunopositive cell numbers were markedly increased in pancreatic islets in study group. In addition to pancreas, caspase-3 immunopositive reaction was higher in liver hepatocyte in study group than controls and strong immunoreactions were observed in kidney tubular epithelial cells (Figures α immunoreactions markedly increased in the study group while the controls were negative. Langerhans islets of pancreas exhibited markedly HIF-1α immunopositive reactions. Slight immunoreaction was detected in hepatocytes of the liver. Strong HIF-1α reaction was observed in both proximal and distal tubular epithelial cells of the kidney in study group (Figures Hyperglycemia and ketonuria was initially observed in both rats in study group 3 days after administration. There were no glucosuria and ketonuria in the control group. Biochemical results of blood and urine were shown in  Figures . Slight  Figures . In both Figures . HIF-1α  Figures . Positiv Figures .β cells of the islets of Langerhans in the pancreas [α, COX-1 and -2, CSR and Caspase-3 by immunohistochemical method.STZ administration to mature rats induces severe and permanent diabetes, with a decrease in insulin levels, to produce a cytotoxic model of diabetes very similar to type I DM. Streptozocin damages pancreas . Streptopancreas . Althougpancreas . This stα in islet of Langerhans, liver, and kidney in streptozotocin induced DM in rats. These results supported the idea that cellular damages due to DM can occur in very early stages of the disease. Our results showed that different mechanisms may play role in diabetes like as hypoxia, apoptosis, and calcium influx in degenerative changes in cells.DM results from the progressive destruction of beta cells of Langerhans islets . Multiplβ cell apoptosis [Caspases are cysteine-aspartyl specific proteases that play a key role in apoptosis . Caspasepoptosis . The undpoptosis . Indeed,poptosis , 28. In Many studies using streptozotocin-induced type 1 diabetic rats have shown an increase in COX-2 production in kidney . Therefo2+ plays a key role in numerous cellular processes, such as maintaining membrane potential and controlling hormonal secretion and cellular proliferation and differentiation [Calcium is known to be an important intracellular messenger. Cantiation . The mecntiation , bone [3ntiation , kidney ntiation , fibroblntiation , antral ntiation , epithelntiation , oligodentiation , renal cntiation . In thisα expression and function in some conditions such as diabetes pathogenesis [α is one of the important members of the bHLH-PAS family [α degradation occurred by HIF prolyl hydroxylases. HIF-1α degradation can be considered cellular oxygen sensors, because their activity varies in the range of physiologic/pathologic oxygen tensions [α [α-negative in the control group's pancreas, increase reaction was seen in the liver and kidney in the study group. The most marked reaction of HIF-1α was observed in Langerhans islets of the pancreas.Hypoxia is the main regulator of HIF-1ogenesis , 36. HIFS family  and funcS family . HIF-1α tensions . It is vsions [α . HIF actsions [α . Diabetesions [α . In the sions [α . Superoxsions [α . In thisα in diabetes-induced rats. These reactions became prominent related to days after induction. The possible cause of the increase may be related to cellular damage by different routes. Increase of severity of the immunoreactions related to days also supported this idea. The most marked reaction was observed in Langerhans islets of pancreas with all of the markers in this study. But liver, and kidney can be affected in very early stages of the disease. These results indicated that cellular damage in DM showed both hypoxia and calcium influx in the cells. Apoptosis can cause marked lesions in organs. This study showed that although diabetes is a chronic disease, its affects can be seen in cells in early stages.As a result, this study showed that marked immunoreaction can be seen in the pancreas, liver and kidney with caspase-3, COX-1, COX-2, CSR, and HIF-1


Patients with low estimated glomerular filtration rate (eGFR) and proteinuria may be at increased risk for stroke. This study investigated whether low eGFR and proteinuria are outcome predictors in stroke patients treated with intravenous thrombolysis.We studied 432 consecutive stroke patients who received thrombolysis from January 2006 to December 2012, in Taiwan. Unfavorable outcome was defined as modified Rankin scale ≥2 at 3 months after stroke. Proteinuria was classified as negative or trace, mild, and moderate to severe. Using logistic regression analysis, we identified independent factors for unfavorable outcome after thrombolysis.p = 0.035; OR = 2.54 for moderate to severe proteinuria, p = 0.035). However, no clear relationship was found between proteinuria and symptomatic hemorrhage after thrombolysis.Of all patients, 32.7% had proteinuria. Patients with proteinuria were older, had higher frequencies of diabetes mellitus, hyperlipidemia, atrial fibrillation, lower eGFR, and greater severity of stroke upon admission than those without proteinuria. Proteinuria, not low eGFR, was an independent predictor for unfavorable outcome for stroke (OR = 2.00 for mild proteinuria, Proteinuria is an independent predictor of unfavorable outcome for acute ischemic stroke in patients treated with intravenous thrombolysis, indicating the crucial role of chronic kidney disease on the effectiveness of thrombolysis. Chronic kidney disease (CKD) is an important global public health issue 2 and poor functional outcome or death Two previous studies revealed that either increased serum creatinine level or reduced estimated glomerular filtration rate (eGFR), was associated with an unfavorable 3-month outcome in stroke patients receiving intravenous thrombolysis This is a multi-center study including one medical center and three community hospitals in Taiwan. All participating hospitals have ongoing stoke registries which were approved by the National Taiwan University Hospital (NTUH) Research Ethics Committee (REC), NTUH Hsin-Chu Branch REC, NTUH Yun-Lin Branch REC, and Landseed Institutional Review Board, to prospectively collect information on acute stroke patients, including initial stroke severity, risk factors, stroke mechanisms, and outcome. All patients gave their written informed consent.This study reviewed consecutive ischemic stroke patients receiving intravenous (IV) recombinant tissue plasminogen activator (rt-PA) from January 2006 to December 2012. Patients were treated for up to 4.5 hours after stroke onset Our study subjects received IV rt-PA dosage that ranged from 0.6 to 0.9 mg/kg, and the standard dosage was defined as 0.9 mg/kg. Based on the Taiwan Thrombolytic Therapy for Acute Ischemic Stroke (TTT-AIS) study, the standard-dose of rt-PA may not be optimal for treating patients with old age and/or severe stroke due to increased risk of symptomatic ICH and mortality −1.154×(age)−0.203× 2 of body surface area.Urine for urinalysis was collected in every patient on admission. If the patient had two or more urinalysis results in the admission course, the one most close to the stroke onset was used. The level of urinary protein was examined using a urine dipstick and was classified into negative (dipstick reading of −), trace (+/−), or positive (1+ to 4+). We categorized the dipstick results into two groups in regard to proteinuria: absence (negative and trace results); or presence (1+ to 4+). The severity of proteinuria was sub-classified as mild  or moderate to severe . The serum creatinine level was obtained at admission. An estimated glomerular filtration rate (eGFR) was calculated using the Modification of Diet in Renal Disease (MDRD) equation: eGFR = 186.3×(serum creatinine)The functional status at 3 months was defined by modified Rankin Scale (mRS) scores. Unfavorable outcome was defined as mRS ≥2. A hemorrhagic event was defined by the evidence of any ICH on the head images within the initial 36 hours. Symptomatic hemorrhage was defined as a neurological deterioration (NIHSS ≥4 points) within 36 hours with no radiological findings that might have been responsible for this deterioration other than a hemorrhage.U-test with relevant variables as indicated. The multivariable logistic regression analysis models were used with unfavorable outcome (mRS ≥2) and hemorrhagic transformation event as the dependent variables. The independent variables entered in the analyses were age, sex, initial NIHSS score, severity of proteinuria, and level of eGFR. Statistical test results were considered significant if p<0.05. Statistical analysis was performed using the SPSS software package version 20.0 .The clinical characteristics according to hospital level , functional outcome, and proteinuria status were compared using the Fisher's exact test, chi-squared test, Student's t-test, and Mann-Whitney 2. One hundred and fifty-five patients (36.0%) had an eGFR<60 mL/min/m2. The median initial NIHSS score was 13. Regarding the dosage administered, 227 patients (52.5%) received a relatively low dose (0.6 to 0.7 mg/kg) of rt-PA whereas the remaining patients received a dose of >0.7 mg/kg of rt-PA. The incidence of hemorrhagic transformation was 22.7%, and the symptomatic ICH was 5.9%. The proportion of patients with a favorable outcome at 3 months was 34.0%. In addition, the NIHSS on admission, functional outcome, and hemorrhagic complications were similar between the medical center and community hospitals  were male. The mean±SD serum creatinine level was 1.17±0.59 mg/dL (102.9±52.7 µmol/L), and eGFR of 68.4±22.7 mL/min/mospitals .P<0.001) and the 3-month mortality rate was slightly higher in the proteinuria group . The occurrence of hemorrhagic transformation was slightly more common in patients with proteinuria , whereas the incidence of symptomatic hemorrhage was not different between the two groups .Urinalysis data were available for 404 patients. There were 132 patients (32.7%) with at least 1+ urinary protein as shown on the urine dipstick exam who were categorized into the proteinuria group. These patients were elderly and had a relatively high prevalence of diabetes mellitus, dyslipidemia, atrial fibrillation, and initial NIHSS score than patients without proteinuria . Unfavorp<0.05, 2 were not significantly related to an unfavorable outcome. In the multivariate logistic regression analysis, the presence of proteinuria remained a significant risk factor, with higher urinary protein levels corresponding to a higher risk of unfavorable outcome , age, sex, presence of atrial fibrillation, presence of proteinuria, and higher NIHSS score were identified as significant factors p<0.05, . Other rThe main finding of our study was that in acute ischemic stroke patients treated with IV rt-PA, proteinuria was strongly related to unfavorable outcome at 3 months, and the effect remained significant even after adjusting for age, gender, and stroke severity. In addition, its detrimental effect was increased proportionally to the level of proteinuria. In contrast, we found that reduced eGFR, based on the creatinine level at admission, was not a predictor of poor functional outcome or hemorrhagic complications.According to previously published reports, several prognostic factors were found consistently to be associated with poor outcome after rt-PA administration, such as older age, higher NIHSS score at baseline, current infarction on baseline imaging scans, high blood glucose, higher blood pressure, or premorbid functional deficits 2 was an independent predictor toward ICH, poor outcome at 3 months, and mortality 2 was not associated with increased ICH, poor functional outcome, or death One Switzerland study involving 196 ischemic stroke patients treated with rt-PA reported that a high initial serum creatinine level was independently associated with a poor outcome (defined as mRS score ≥3) at 3 months 2 was not a predictor of unfavorable outcome or hemorrhagic transformation. As demonstrated by a large population-based study, the graded risk of cardiovascular events and mortality rose sharply for subjects with an eGFR<45 mL/min/m22 was used as a cut-off point for impaired renal function, eGFR was still was not associated with an unfavorable outcome for ischemic stroke.In our study, the commonly used indicators for renal dysfunction such as serum creatinine, blood urea nitrogen, or eGFR level were not different between favorable and unfavorable outcome groups. An eGFR<60 mL/min/mProteinuria is increasingly being recognized as an indicator and as a screening tool for CKD The exact mechanism by which proteinuria is independently associated with unfavorable outcome after rt-PA-treated ischemic stroke is unclear. First, the presence of albuminuria is a predictor of hemorrhagic transformation after ischemic stroke, including those treated with intravenous thrombolysis There are some limitations of our study. First, not every patient receiving thrombolytic therapy had a urine dipstick examination, resulting in a slightly smaller sample size than initially expected. Even though, we found that proteinuria was still more important than eGFR in predicting functional outcome of thrombolytic patients at 3 months after stroke if we only analyzed the patients receiving both eGFR and urine examination (404 of 432 patients). Second, eGFR and proteinuria were determined by creatinine levels and urinary dipstick results at admission, which may have been affected by acute stroke effects. The possibility of transient proteinuria cannot be excluded. A pre-stroke evaluation and even repeated urinary examination would be desirable to abate the influence of stroke. Third, the urinary dipstick analyses were quasi-quantitative, and not standardized in our participating hospitals. Although the dipstick test is cost-effective and simple, its sensitivity is not always high enough since it is useful only for urinary protein >300 to 500 mg/day. Thus, it would more precise to evaluate the presence of micro albuminuria or urinary albumin-to-creatinine ratio.In summary, our study demonstrated that proteinuria was an independent predictor of an unfavorable outcome after rt-PA treatment of acute ischemic stroke patients. A further prospective study is indicated to delineate the precise relationship between proteinuria or micro albuminuria and stroke outcome after rt-PA administration. In patients with proteinuria, further randomized controlled trials might be warranted to see if additional therapeutic strategies to reduce proteinuria would improve the efficacy of thrombolysis.Table S1Demographics comparison between medical center and community Hospitals.(DOCX)Click here for additional data file.Table S2Univariate analysis of unfavorable outcome.(DOCX)Click here for additional data file.


Acute colonic obstruction is the most common complication of colorectal cancer (CRC) in elderly patients. Medical treatment has been associated with higher perioperative morbidity and mortality rates. There is a need for identification of elderly CRC patients who will do poorly so that results can be improved. The purpose of this study is to assess the 30-day outcome of elderly patients undergoing malignant colonic obstruction procedures and identify the associated factors of mortality.A review of 233 elderly patients who received medical procedures for malignant colonic obstruction between April 2000 and April 2012 was conducted. Data regarding clinical variables, surgical procedures and outcomes, complications, and mortality were studied. Univariate and logistic regression analyses were performed on mortality risk factors.Patients had a mean age of 78.2 years (range 70–95). A total of 126 (54.1%) patients were classified ASA III and above. Eighty (34.3%) patients had right-sided colonic obstruction. In the 153 (65.7%) patients with left-sided colonic obstruction, 40 patients received self-expandable metallic stent (SEMS) treatment and 193 patients received surgery. A total of 62.2% (n = 145) patients had post operation complications. The overall 30-day mortality was 24.5% (n = 57). ASA grading, peritonitis and Dukes staging were independent risk factors for mortality.Medical procedures in elderly patients with malignant colonic obstruction are associated with significant complications and mortality. Identifying these high-risk patients and treating promptly may improve outcomes. SEMS treatment provides a useful alternative to surgical intervention. Acute colonic obstruction is the most common complication of colorectal cancer (CRC) in elderly patients. The incidence of complete obstruction has been reported to be as high as 30%, and this complication can result in perforation, sepsis, and even death -3. SurgeThe purpose of this study is to assess the 30-day outcomes of elderly patients undergoing malignant colonic obstruction procedures and, more importantly, to identify the associated risk factors for mortality in this complex group of patients.From April 2000 to April 2012, we studied retrospective data of consecutive elderly patients (aged ≥70 years) who were diagnosed with acute malignant colonic obstruction and were admitted to the General Surgery Department on an emergent basis. All patients had histologically proven intrinsic colorectal adenocarcinoma. 21 patients with metastatic CRC were excluded. After attempting conservative management with nasogastric suction and intravenous fluid replacement for 24–48 h, 233 patients failed to respond medical management and underwent either SEMS treatment or surgery. Of the 233 patients, 40 with acute left-sided colonic obstruction successfully received SEMS treatment. Placement of SEMS was performed as described previously [Data regarding the patient’s clinical features, treatment outcomes including 30-day morbidity and mortality, and follow-up information were obtained from a clinical database. We then evaluated clinical factors that could be associated with mortality. The variables included the followinig: age, sex, concurrent illness, time between onset of symptoms and surgery, American Society of Anesthesiologists (ASA) grading, location of obstruction, type of treatment, operative findings , Dukes staging, and major morbidities. Diagnosis of peritonitis is based upon a clinical history compatible with peritonitis, and an exam in which the abdomen is tender to touch. In addition to pain, the abdomen is rigid and bowel sounds are absent. Mortality was defined as that occurring within 30 days postoperatively.All treatment interventions applied in this study including SEMS are officially approved, and are routine therapeutic options for old patients in China. Accordingly, prior to the initiation of the treatments, this work was approved by ethics committee at Shanghai Jiaotong University Affiliated The Six People’s Hospital.Statistical analyses were performed using SPSS software . Univariate analysis was performed with the chi-square test. Mann–Whitney U test and Fisher exact test were applied where required. Covariates that remained significant through univariate analysis were selected for multivariate analysis. Forward stepwise logistic regression with P < 0.1 for inclusion and P > 0.05 for exclusion was performed to evaluate mortality. The results were evaluated at a confidence interval of 95%, and significance was set at P < 0.05.There were 233 patients in this study with a mean age of 78.2 years (range 70–95). Patient characteristics including gender, time from onset of symptoms to surgery, and ASA grading are shown in Table Surgical observations are shown in Table One hundred fifty-three (65.7%) patients presented with left-sided colonic obstruction. Forty (26.1%) of these patients successfully received SEMS treatment. Following SEMS insertion, staging and systemic evaluation of fitness for operation was performed. Seven of the 40 patients (17.5%) were considered ineligible for surgery because of serious comorbidities, and in these patients, SEMS was used as permanent palliative therapy. The remaining 33 of the 40 (82.5%) patients successfully received SEMS as a bridge to surgery. Tumor resection and primary anastomosis were performed in 30 (75.0%) patients, and Hartmann’s procedure was performed in 3 (7.5%) patients. Surgery was performed in 113 (73.9%) patients. RPA (resection + primary anastomosis) was performed in 49 (43.4%) patients and RS (resection + stoma) was performed in 44 (38.9%) patients. Twenty (17.7%) patients received palliative colostomy procedures.A total of 62.2% (n = 145) patients had post operation complications of some kind. Local and systemic complications occurred in 15.5% n = 36) and 46.8% (n = 109) respectively . In left-sided colonic obstruction, a lower mortality (7.5%) was found in patients who received SEMS compared to patients who received surgical treatment (28.3%) (p < 0.01). Univariate analysis of risk factors for mortality showed that time from onset of symptoms to surgery, ASA grading, intra-operative findings, Dukes staging, and systemic morbidity reached statistical significance (Table Colorectal cancer is predominantly a disease of elderly people and is a major cause of morbidity and mortality in the elderly population . AnalysiSurgery for malignant colorectal obstruction poses several problems. Elderly patients often have an increased incidence of comorbid conditions. However, in subgroups of aged patients undergoing surgery, there has been no evidence of increased comorbidity with increased age . Our stuThe placement of a metallic stent in the colon was first reported by in 1991 by Dohmoto . Since tAs in previous reports, for emergent surgery in the unprepared left-sided colon, RS is still one of the best operative alternatives, especially in elderly patients -18. In oManagement of obstructing colorectal cancer remains strongly associated with poor outcomes. Ozturk reported in a multivariate logistic regression analysis that colorectal disease increased the risk of death by ninefold in elderly patients undergoing surgery . EmergenThe first objective of our study was to identify correlates of poor clinical outcomes as possible risk factors in elderly patients who received treatment of colorectal obstruction. Univariate analysis found that high mortality was associated with time from onset of symptoms to surgery, ASA grading, presence with peritonitis or perforations, Dukes staging and systemic morbidity. Logistic regression analysis was used to test for the possibility of all these collected parameters to predict the poor outcome. As reported by previously published studies, ASA grading was found to be the most important determinant of mortality ,20. PhysThe term ‘getting old’ may be defined as ‘an inherent, progressive impairment of function with the passage of time, which cannot be averted, and which causes individuals to become more vulnerable to death’ . But it In order to prevent high mortality, it should be emphasized that in elderly patients who require operation for colorectal cancer, the operation should be performed as soon as conditions are optimized and should not be postponed. When malignant colonic obstruction occurs, identifying these high-risk patients and treating them promptly rather than delaying or denying surgery is the best option. Also SEMS may provide a useful alternative to surgical intervention in the management of acute left-sided colorectal obstruction for elderly patients.The authors declare that they have no competing interests.MG: concept, design, data analysis, manuscript writing and editing. YF: concept, design, data analysis, manuscript writing. JL: concept, design, data analysis, manuscript writing and editing. QZ: concept, design, manuscript editing. JD: statistical analysis. YW: design of the study. YF: manuscript editing. XYH: concept, design. All authors read and approved the version to be published.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-230X/14/76/prepub


Objectives of this study were to evaluate glomerular filtration rate (GFR), renal structural changes and proteinuria in aged Beagle dogs before and after hydrocortisone (HC) administration. Eleven Beagle dogs ≥10 years old were treated with either hydrocortisone  or placebo . Urinary markers, GFR and kidney biopsies were evaluated before (T0), during (T16 wks) and after discontinuing HC administration (T24 wks). Results indicate that HC administration causes a significant increase in GFR. At all time points except T16 wks, proteinuria was higher in the control group than in the HC group, and there was no significant difference in urinary markers between groups. At T16 wks, proteinuria, urinary albumin-to-creatinine (c) ratio, immunoglobulin G/c and retinol-binding protein/c were higher compared to baseline in the HC group. At T0, rare to mild renal lesions were detected in all HC dogs and rare to moderate changes in all control dogs. Glomerulosclerosis progressed in both groups until T24 wks. Tubular atrophy was detected in three HC dogs at T16 wks and T24 wks, but also in five control dogs throughout the study. At every time point, five HC dogs and all control dogs had rare to moderate interstitial inflammation. Rare to mild interstitial fibrosis was found in up to three HC dogs at T16 wks and T24 wks, and severe fibrosis in one HC dog at T24 wks. Up to four control dogs had rare to mild fibrosis at all time points. These findings indicate that clinically healthy, aged Beagle dogs may have considerable renal lesions and proteinuria, which could have implications for experimental or toxicological studies. Additional research is needed to elucidate glucocorticoid effects on renal structure, but functional changes such as hyperfiltration and proteinuria warrant attention to kidney function of canine patients with Cushing's syndrome or receiving exogenous glucocorticoids. Proteinuria has been described in 44–75% of dogs with Cushing's syndrome and sometimes persists or even develops after successful treatment of hypercortisolism Canine endogenous hypercortisolism or Cushing's syndrome is considered a good animal model for its human counterpart, because of similarities in the pathogenesis : 80–85% of cases are caused by a pituitary tumor and ACTH-dependent, while 15–20% are ACTH-independent in vivo situation in spontaneous Cushing's syndrome. For example, many experiments included young animals Previous experimental studies evaluating GC effects on renal function often differed from the In addition to serum renal markers and GFR, urinary markers are gaining interest in veterinary medicine, because of their potential for early detection of renal dysfunction and ability to localize the insult to a particular part of the nephron Information about GC effects on renal function and morphology is rare, and often limited to case reports, despite their frequent therapeutic use and the occurrence of Cushing's syndrome in humans and dogs 2 each, with free access to water, fed a standard dry food twice a day , and allowed outdoor activity in a secured area. They were judged healthy based on physical examination, hematology, biochemistry profile, abdominal ultrasound and two consecutive morning urinary corticoid-to-creatinine ratio's (<10*10−6) to exclude endogenous Cushing's syndrome. A urinalysis consisting of sediment and dipstick analysis, urine specific gravity (USG), urinary protein-to-creatinine ratio (UPC), and bacterial culture were performed, but proteinuria (UPC>0.5) was not an exclusion criterion.This study was approved by the Ethical Committee of Ghent University (EC: 2008/146). Eleven female spayed Beagle dogs, age 8.4 to 11 years (median: 10 years), with a body weight ranging from 10.9 to 14 kg (median 12.9 kg) were included in the study. Dogs were housed in pairs in two adjacent indoor kennels of 2.6 mFive dogs were randomly assigned to the placebo group (control group) and six to the hydrocortisone treatment group (HC group). After baseline sampling (T0), the control group received a gelatin capsule containing lactose and the HC-group received a capsule containing lactose and a median dose of 9.6 mg/kg HC (range from 8.7 to 11.0 mg/kg) every 12 hours (h). Hydrocortisone was used because it is the synthetic glucocorticoid most closely resembling endogenous cortisol and dosage was based on two previous publications At T16 wks and T24 wks, an ACTH-stimulation test was performed in all dogs by collecting serum for measurement of cortisol before and 60 minutes (min) after intramuscular injection of 0.25 mg of synthethic ACTH . Cortisol concentrations were measured using an immunoassay validated for use in the dog .Morning urine samples were taken by cystocentesis . Urinary dipstick analysis , urine specific gravity (USG), urinary protein-to-creatinine ratio (UPC), sediment analysis and bacterial culture were performed. After centrifugation, the urine supernatant was stored at −80°C until analysis of urinary markers.ad libitum. Glomerular filtration rate was measured by plasma clearance of exogenous creatinine (Clcreat), exo- and endo-iohexol (Clexo and Clendo), adapted from a protocol previously proposed in cats All dogs were fasted for at least 10 h prior to the test day and fed immediately after ending the sampling period. Water was provided Plasma creatinine (Cr) concentrations were analysed using an enzymatic method . This technique was validated by measuring samples with increasing Cr concentration 4 times per day, on each of 3 consecutive days. The upper limit of quantification was 1202 µmol/L. Within- and between-day coefficients of variation were <3% in the lower, middle, and high concentration range , and there was linear correlation between theoretical and measured concentrations within quantification limits. The basal plasma Cr concentration measured on the day of PEC-ICT testing was subtracted from the Cr concentrations measured in the samples from that dog.Plasma concentrations of iohexol stereo-isomers (exo- and endo-iohexol) were determined by a validated high-performance liquid chromatographic method with ultraviolet detection, as previously described creat, Clexo and Clendo were determined by dividing the actually administered dose of exogenous creatinine, exo- and endo-iohexol, respectively, by the corresponding AUC, and indexation to bodyweight (mL/min/kg).Pharmacokinetic analyses were performed using WinNonlin . For clearance calculation, individual plasma data were subjected to noncompartmental analysis, as described by Watson and coworkers Serum Cr (sCr)  and urea  were measured using an enzymatic method. Urinary protein was determined with a turbidimetric method using benzethonium chloride, and urinary creatinine with a modified Jaffé reaction using picric acid . As markers of glomerular function, urinary (u) ALB and uIgG concentrations were determined with a commercial canine specific enzyme-linked immunosorbent assay (ELISA) . As an indication of tubular function, uRBP was determined with a human ELISA  and uNAG activity using a colorimetric assay . All assays had been previously described and validated in our laboratory Coagulation was checked in all dogs by measurement of buccal mucosal bleeding time, and activated partial thromboplastin and prothrombin time . Ultrasound guided percutaneous kidney biopsies were taken under general anesthesia at T0, T16 wks and T24 wks. Dogs were premedicated intravenously (IV) with a combination of acepromazine (0.01 mg/kg)  and butorphanol (0.01 mg/kg) . Afterwards, dogs received IV diazepam (0.2 mg/kg)  immediately followed by propofol  to effect until endotracheal intubation could be performed. Anesthesia was maintained with isoflurane (2% vaporized in 100% oxygen) .Ultrasound guided kidney biopsies were taken by an experienced radiologist, according to a previously described technique Three µm sections from each biopsy sample were stained with hematoxylin and eosin (HE), periodic acid-Schiff (PAS), Masson's trichrome and periodic acid methenamine silver. All biochemical stains were performed according to standard procedures For direct immunofluorescence (IF) examination, fresh unfixed renal specimens were embedded in OCT compound, snap-frozen in liquid nitrogen and stored at −80°C. Subsequently, 5 µm thick sections were fixed with acetone for 15 min. After washing with PBS (two passages), slides were incubated with FITC-labelled sheep anti-dog IgG, goat anti-dog IgM, goat anti-dog IgA, goat anti-dog C3 , rabbit anti-human κ light chain, rabbit anti-human λ light chain, and rabbit anti-human complement factor C1Q . Primary antibodies were omitted as negative controls and substituted with PBS For transmission electron microscopy (EM), the tissue was post-fixed in 2% osmium (in distilled water) for 1.5 h, dehydrated in graded acetone and embedded in epon. Semi-thin sections were stained with azure methylene blue. Ultrathin sections were counterstained with uranyl acetate and lead citrate. For ultrastructural studies, a Philips EM 420 was used. All histological sections were examined in a blinded fashion by three pathologists.Analyses were performed with a commercial software program . Level of significance was set at 5%. A general linear model was used to test the effect of HC treatment, time point and their interaction between the control and the HC group. When a statistically significant interaction between treatment and time point was detected, a post hoc hypothesis test was performed to compare the two groups at each period.p<0.001).All dogs assigned to the HC group developed clinical signs of hypercortisolism, such as polyuria, polydipsia and skin changes  and complementary laboratory changes . Additionally, some dogs also developed muscle atrophy and abdominal distention, but no significant changes in bodyweight were detected throughout the study. At T16 wks, 36 h after HC withdrawal, all dogs in the HC group failed to respond adequately to ACTH-stimulation; median (range) serum cortisol concentrations before and after ACTH-injection were 18 nmol/L (6–30 nmol/L) and 25 nmol/L (17–86 nmol/L). At T16 wks serum ALT was significantly increased in the HC group compared to the control group . Response to an ACTH-stimulation test was within normal range in all dogs; median (range) serum cortisol concentrations before and after ACTH-injection were 32 nmol/L (25–60 nmol/L) and 330 nmol/L (246–516 nmol/L).creat and Clexo were significantly higher in the HC group than in the control group at T16 wks (p<0.001). There was no significant difference between groups either at baseline or at T24 wks. Plasma Clendo was not significantly different between groups at any time point (p = 0.21). As presented in p = 0.74), urea concentration (p = 0.32) and USG (p = 0.30) throughout the study, despite a decrease of USG during treatment in the HC group. Urinary protein-to-creatinine ratio was significantly higher in the control group than in the HC group (p = 0.003) at baseline, T4 wks, T20 wks and T24 wks, but not at T16 wks. th percentiles of UPC, uALB/c, uIgG/c, uRBP/c and uNAG/c in the HC and control groups before, during and after HC administration, with the grey area representing the treatment period. Differences between HC and control groups in glomerular markers uALB/c (p = 0.05) and uIgG/c (p = 0.26) did not reach statistical significance, although they progressively increased within the HC group during treatment and decreased afterwards. Also for tubular markers uRBP/c (p = 0.07) and uNAG/c (p = 0.20), there was no significant difference between the HC and control groups at any time point, despite the fact that uRBP/c seemed to increase within the HC group, with highest concentrations at T16 wks, and declined again after discontinuation of HC.As shown in Most important light microscopic findings in HC and control dogs are presented in Commonly observed glomerular lesions were global endocapillary and mesangial hypercellularity, with increase of mesangial matrix. Increase of mesangial matrix progressed in both the HC and control group at T16 wks and T24 wks, with an increasing number of affected dogs and highest scores at T24 wks . ObsolesUltrastructural lesions included changes of the glomerular basement membrane (GBM) such as thickening, rarefaction, wrinkling and irregular jagged profile . At T0, Due to a technical error concerning the Michel's transport medium, biopsies could not be evaluated with IF at T0. Immunofluoresence staining at T16 wks and T24 wks was unremarkable with coarse, segmental deposits of Ig G (1+ to 2+) in the capillary wall in 1/6 HC dogs and 2/5 control dogs at T16 wks. Mesangial Ig M deposits (1+ to 2+) were detected in 4/6 HC dogs and 3/5 control dogs at T16 wks, and in one control dog at T24 wks. Coarse λ light chain deposits (1+ to 2+) were seen in the capillary walls and mesangium of one dog from each group at T16 wks, and in one control dog at T24 wks. One dog from the HC group had 1+ coarse, diffuse, segmental deposits of C3 at T24 wks.In summary, glomerular, tubular and interstitial lesions presented in creat and Clexo were both significantly increased in the HC group at T16 wks, but no longer differed between groups eight weeks after tapering and cessation of treatment. This is in agreement with previous reports showing that synthetic GC augment GFR in dogs, with an increase in renal plasma flow (RPF), renal vasodilation and a decrease in filtration fraction (FF) This study demonstrates that HC administration reversibly increases GFR in aged Beagle dogs. Plasma ClAlthough all dogs included in the study were clinically healthy with no abnormalities on hematology, biochemistry profile and abdominal ultrasound, two dogs from the HC group and four dogs from the control group had an increased UPC at baseline. Proteinuria, which did not progress over a two year follow-up period, has been previously described in otherwise healthy Beagles by Stuart and coworkers Proteinuria was significantly higher in the control group than in the HC group at all time points, except for T16 wks. This could be caused by an increase in UPC in the HC group at the end of the treatment period. Possible mechanisms causing glomerular proteinuria include glomerular hypertension and structural alterations of the glomerular barrier At baseline, many dogs had mild to moderate pre-existing renal lesions. Glomerulosclerosis has been described to be age-related in dogs and in people At the end of the HC administration period, most striking LM findings in the HC group, not detected at baseline, were obsolescent glomeruli and tubular atrophy. However, there was a higher prevalence of renal lesions at baseline than expected and glomerular, tubular and interstitial changes also progressed in the control group. Therefore, it is not possible to separate HC effects from progression of pre-existing renal lesions. It is possible that HC administration accelerated age-related glomerulosclerotic and tubular changes in the HC group, but definitive conclusions cannot be drawn from these data. Another limitation of the study is the lack of IF examination at baseline. However, IF findings at T16 wks and T24 wks were either mild or non-specific. For example, the mesangial IgM deposits detected in some HC and control dogs at T16 wks and in one control dog at T24 wks were probably due to entrapment of IgM in sclerotic glomeruli.In conclusion, this study shows that HC administration reversibly increases GFR, with a similar trend for proteinuria. Results indicate that clinically healthy aged Beagle dogs have renal lesions and proteinuria, which could have implications for experimental or toxicological studies. Although further research is needed to elucidate whether morphological renal changes are GC-induced, hyperfiltration and proteinuria are, and warrant attention to kidney function in human and canine patients with Cushing's syndrome or receiving exogenous GC.


Vigna. unguiculata. ssp sesquipedalis) is a subspecies and special vegetable type of cowpea  important in Asia. Genetic basis of horticulturally important traits of asparagus bean is still poorly understood, hindering the utilization of targeted, DNA marker-assisted breeding in this crop. Here we report the identification of quantitative trait loci (QTLs) and epistatic interactions for four horticultural traits, namely, days to first flowering (FLD), nodes to first flower (NFF), leaf senescence (LS) and pod number per plant (PN) using a recombinant inbred line (RIL) population of asparagus bean.Asparagus bean (A similar genetic mode of one major QTL plus a few minor QTLs was found to dominate each of the four traits, with the number of QTLs for individual traits ranging from three to four. These QTLs were distributed on 7 of the 11 chromosomes. Major QTLs for FLD, NFF and LS were co-localized on LG 11, indicative of tight linkage. Genome wide epistasis analysis detected two and one interactive locus pairs that significantly affect FLD and LS, respectively, and the epistatic QTLs for FLD appeared to work in different ways. Synteny based comparison of QTL locations revealed conservation of chromosome regions controlling these traits in related legume crops.Major, minor, and epistatic QTLs were found to contribute to the inheritance of the FLD, NFF, LS, and PN. Positions of many of these QTLs are conserved among closely related legume species, indicating common mechanisms they share. To our best knowledge, this is the first QTL mapping report using an asparagus bean × asparagus bean intervarietal population and provides marker-trait associations for marker-assisted approaches to selection. V. unguiculata L. Walp.) is an important grain legume, fodder and vegetable crop in many tropical and subtropical regions of the world [V. unguiculata ssp. sesquipedialis), also known as ‘yard long’ bean or snap bean is a subspecies and distinctively domesticated type of cowpea grown mainly for vegetable use in many Asian countries. Asparagus bean, together with the African cowpea (V. unguiculata ssp. unguiculata), forms the two main divisions of cultivated cowpea [Cowpea  for FLD and LS at a significant level of p=0.0001 Table . CorrelaQfld.zaas-11, was detected on LG11 in all environments with the LOD scores ranging from 5.3 to 10.6  and multiple-mode QTL mapping (MQM) . Estimated with the closest locus 1_1103, the ZJ282 allele of this QTL lowered the number of node to first flower by 21% in the three trials. Apart from Qnff.zaas-11, one more QTL, Qnff.zaas-4, was detected on LG4 with a LOD score as high as 3.23 in HN2009  in the four trials. On LG2, another QTL, Qpn.zaas-2, was detected in SX2010 (LOD=3.56). This QTL was also detectable in HN2010 but with lower LOD score (2.28). The DNA markers closest to the QTL peaks were only 4.1 cM apart between the two locations. Qpn.zaas-2 had a moderate effect on PN, as revealed by the average phenotypic variation (16.1%) it explained. The Qpn.zaas-2 allele with a positive effect on pod number was also carried by ZN016.A major QTL, .5 Table . This QTQpn.zaas-4 on LG4 accounted for 11.3% of the phenotypic variation and was considerd a plausible minor QTL for PN  was in the Qfld.zaas-11 interval (2.2 cM apart to the peak), while the other was not independently related to FLD. For LS, the interactive pair of loci detected included a locus (Clm1135) in the peak region of the major QTL Qls.zaas-11 and an independent locus on LG 8.Three and only one pair of loci showing significant epistatic interactions were detected in at least two of the four trials for the traits FLD and LS, respectively Table . In each1_0514/1_0542 on LG 6 interacted differently from that harboring Clm0364 on LG 5 with QFld.zaas-11. In the presence of the ZJ282 allele of QFld.zaas-11, the co-existence of the ZN016 allele of 1_0514/1_0542 shortened FLD significantly (P = 0.01) than of the corresponding ZJ282 allele  and QTLs showing epistatic effects only (epQTLs). Interestingly, we found the epistatic interaction could be in either coupling phase or in repulsion phase, depending on the locus, suggesting that some loci are co-adapted during domestication/speciation and that loci favorable for breeding purpose may exist in both improved cultivars and landraces. In other plant species including, soybean ,17, oilsQfld.zaas-11 and Qls.zaas-11 alleles from either parent had accordant effects , this may also explain why almost all early flowering progenies were prematurely senesced. In two inter-subspecies crosses, QTLs for the traits of organ sizes  [Lf) for flowering time was reported to coincide with a QTL associated with NFF [Significant correlations were found among FLD, NFF and LS, which are indicative of related or pleiotropic genetic factors governing these traits. This was then verified by the co-localization of major QTLs for these traits on LG11. Given that the nd leaf) , were alwith NFF . Isemurawith NFF .Qfld.zaas.10 and the soybean flowering time QTL QFT04 in Chr 16 (LG J)  Figure , which i VuLG 11 , two QTL VuLG 11 . Regardi VuLG 11 , there h VuLG 11 . In comm VuLG 11 . Taken t1, O and D1b+w[Genetic basis of NFF and LS have been rarely characterized in legumes thus far. A single large effect QTL for NFF was detected in VuLG 2 based on an AFLP-based genetic map . Accordiand D1b+w; from thQls.zaas-11 would at the same time delay flowering. Thus, more precisely dissecting the linked QTLs or screening for germplasm with unlinked QTLs is necessary. Fortunately, flowering-independent control of leaf senescence has been reported in Arabidopsis[The identification of QTL positions in the current study has laid a preliminary foundation for maker assisted selection (MAS) for asparagus bean; however, there is still a long way to go to achieve practically efficient MAS in the field, as 1) the QTL intervals are still large; 2) although a few minor QTLs were identified for each trait, many of them showed relatively low LOD scores or were environment-dependent. Further validation of these minor QTLs are necessary before utilizing them in breeding; 3) epistatic interactions are present for certain traits; and 4) co-location of QTLs may affect pyramid of desired traits. Here, even though ZN016 carries desired QTLs conferring delayed senescence and greater pod number per plant, the effort to introgress, for instance, the major abidopsis. If the To assist narrowing QTL intervals, some recent resources available for cowpea can be used. These include a denser consensus genetic map of cowpea ,7, a uniIntrogressing favorable alleles is more easily accomplished by intervarietal crossing than by incorporating far-related resources such as wild progenitors. Therefore, dissecting genetics of horticultually important traits in an intervarietal population is not only theoretically useful, but can direct us to rapidly choose appropriate DNA markers to aid selection. The ‘ZZ’ map, which integrated genic SNPs and user-friendly SSR markers is particularly useful in this regard. The mapping of QTLs including epistatic loci for four horticulturally important traits in the current study solidified the basis for implementing marker-assisted breeding toward genetic improvement of asparagus bean.8:9 recombinant inbred lines (RILs) produced by single seed descent from the cross of asparagus bean varieties ‘ZN016’and ‘ZJ282’ were used for collecting phenotypic data. ‘ZN016’ is a landrace asparagus bean accession originating from Southern China while ‘ZJ282’ is a commercial cultivar grown nationwide.Two hundred and nine F′N, 120°41′E) and the other in Shaoxing , which are ~ 150 km apart. Except for the SX2009 trial that had no biological replicate, each experiment consisted of two replicates. For each plot ten seeds per RIL line were planted every 28 cm in 25 m-long plots on rows 75 cm apart, but only four uniform seedlings per line were retained after seedling emergence because of the big size and strong climbing habit of adult asparagus bean plants that are difficult to manage. Twelve healthy seedlings of each of the parental lines were set for each experiment. Aside each plant, a bamboo pole was erected to support plant climbing. The plots were spaced by 50 cm to avoid border effect.Four field trials were performed in 2009 and 2010 in a randomized complete block design at the normal planting season. The dates for seed sowing for each experiment were: HN2009, 16th April; SX2009, 28th April; HN2010, 28th April; SX2010, 29th April. In each year, one trial was carried out in Haining , nodes to first flower (NFF) on the main stem, pod number per plant (PN) and leaf senescence index (LS). FLD and NFF were both recorded on a daily basis from the beginning of flowering until the latest flowering line had flowered. PN and LS were always scored on the same day, when were 78 and 81 days after sowing in 2009 and 2010, respectively. No new pod emerged after the dates of scoring. LS was scored using a visual index ranging from 0 to 5 expressed as a percentage, where 0 was no sign of leaf senescence (complete green) and 5 equaled 100% leaf senescence (complete yellow). Indices from 1 to 4 were: 1 ≤ 20%, 2≤40%, 3≤40%, 4≤80% of leaf senescence. Data except for NFF of the 2010SX trial were collected for both replicates of all trails.2 = σg2/(σg2 + σe2), using variance components estimated based on ANOVA, where σg2 is the genetic variance and σe2 is the experimental error.Data from all the 209 lines were analyzed for frequency distribution using the software Statistica 6.0 , and for correlation and analysis of variance (ANOVA) using Data desk v.6.2 . Pearson’s correlation coefficients among trials were investigated using the mean phenotypic data for the two replicates of each trail. The broad-sense heritability was calculated with the formula hA subset of 96 lines of the RIL population, which had been previously genotyped by SNP and SSR markers to construct the ‘ZZ’ genetic map was used for QTL mapping . SoftwarP-value cutoff was set as 1 × 10-5 for the total effects and 0.01 for the interaction effects of two examined loci. The statistical significance threshold for each trail was determined by 1,000 random permutations (highly significant) under the additive model with interaction.The genome wide two-locus epistasis interactions were surveyed using the ‘interactions’ function implemented in the software Map Manager QTXb20 . The P-vThe authors declare that they have no competing interests.Experiments were designed by PX and GL. XW and BW constructed the RIL population. All authors participated in field traits evaluation. PX and TH analyzed all the data and performed statistical analyses. PX drafted the manuscript and GL contributed by critical reading. All authors read and approved the final manuscript.Across-trait correlation coefficiencies in different trials.Click here for file


HIV-infected individuals are at risk for decreased bone mineral density (BMD). The known risk factors for bone loss do not fully explain the increased risk in this population. There is emerging evidence that leptin, a hormone secreted by adipocytes, plays an important role in bone metabolism. Several studies have assessed the relationship between leptin and bone density in healthy adults, but there are few such studies in HIV-infected individuals. Furthermore, HIV infected individuals on antiretroviral therapy are at increased risk for altered fat distribution, which may impact the relationship between leptin and BMD. In a cross-sectional analysis of data in 107 HIV-infected men, we determined whether serum leptin levels were associated with whole-body BMD and bone mineral content measured by dual-energy X-ray absorptiometry (DEXA), after adjusting for confounders including body fat distribution. We found an inverse association between leptin and bone density in those with peripheral lipoatrophy, defined objectively as <3 kg appendicular fat by DEXA, but no such relationship was seen in those with >3 kg appendicular fat. This result suggests that fat distribution may modify the relationship between leptin and bone density. Patients with HIV infection are at risk for decreased bone density . This isWhereas cross sectional studies in healthy women have consistently shown a positive association between leptin levels and bone mineral density (BMD) –8, studiWe performed a retrospective, cross-sectional analysis of data in 107 HIV-infected men who underwent whole-body dual X-ray absorptiometry (DEXA) scan and fasting blood draws at the Clinical Research Center (CRC) at San Francisco General Hospital (SFGH) between 1998 and 2002. The subjects completed these assessments either during participation in an observational cohort study  or at scTotal body fat, lean body mass (LBM), BMD, and BMC were determined by whole body DEXA scan . Manual analyses of appendicular (arm + leg) and trunk fat were performed using soft-tissue and skeletal landmarks . Serum testosterone levels were measured by radioimmunoassay . Fasting serum leptin and insulin concentrations were measured by radioimmunoassay  as previously described . Blood f+ SD or median (interquartile range [IQR]) for skewed variables were calculated. We performed bivariate analysis using scatter plots and linear regression for numerical predictors, and chi-square test for dichotomous predictors. The dichotomous predictors included race (Caucasian/non-Caucasian) and antiretroviral medications (yes/no) as described below. We then performed multivariate analyses to account for confounders. Potential confounding variables were identified a priori and included total body fat, percent body fat, trunk fat, appendicular fat, lean body mass (LBM), percent LBM, testosterone levels, years of HIV infection, CD4 count, and classes of antiretroviral medications. If the covariate was associated with BMD or BMC with a P-value <0.05 in univariate analyses, it was included within the multivariate model. Age and race were always included as covariates in the multivariate models. We first performed multivariate analysis in the entire population. We then performed further analyses in subjects with lipoatrophy, using the objective definition of Martínez et al. [Our primary outcomes were whole body BMD and BMC, and the primary predictor was serum leptin. We examined the distribution of all variables; those with skewed distribution were natural log transformed. Mean z et al.  of <3 kg2, and body fat of 15.0 ± 7.5% (μL (IQR 243–583) and average duration of HIV infection was 11 ± 5 years. The study population included a wide range of body sizes, as reflected by the range of weight (47–106 kg), BMI (16.9–38.6 kg/m2), total body fat (3.1–35.3 kg), trunk fat (1.2–20.8 kg), and appendicular fat (1.5–14.3 kg). The median leptin concentration was 3.2 ng/mL (IQR 2.1–5.7). Leptin and total body fat were moderately correlated .A total of 107 HIV-infected men were included in the study; 69% were Caucasian, with a mean age of 46 ± 9 years, BMI 25.1 ± 3.6 kg/m0 ± 7.5% . One hunIn univariate regression, there was no statistically significant association between age, race, percent body fat, percent LBM, testosterone level, years of HIV infection, CD4 count, PI, NRTI, or NNRTI use and BMD or BMC. On the other hand, LBM and total body fat, as well as appendicular and trunk fat, were significantly positively associated with both BMD and BMC. Serum insulin was positively associated with BMD, but not BMC. P-value for linear trend =0.11 and 0.15 for BMD and BMC, resp.). In the group as a whole, we found no statistically significant association between natural log-transformed leptin levels and total BMD or BMC in either bivariate analysis or multivariate analyses . To asseP = 0.01). Thirty-three subjects met the definition of peripheral lipoatrophy (<3 kg of appendicular fat). In this group, we found a robust and statistically significant inverse relationship between circulating leptin concentrations and both BMD and BMC . This stn = 74), there was no significant relationship between leptin and bone density. Further analysis by tertiles of appendicular fat  revealed no significant association between leptin and bone mineral density in the upper two tertiles . To determine whether leptin was a surrogate marker for appendicular fat, we assessed the association between appendicular fat and bone density. After adjustment for confounders , there was no statistically significant relationship between appendicular fat and whole body BMD or BMC. In subjects with >3 kg of appendicular fat (n = 107), or in the subgroups . Addition of serum insulin concentrations to the multivariate analysis did not significantly change any of our results (data not shown), either in the entire cohort (In this analysis of data in a diverse group of 107 HIV-infected men, we found no statistically significant relationship between serum leptin levels and whole-body BMD or BMC. However, in the 33 subjects with <3 kg of appendicular fat, we found a robust inverse association between leptin and bone density that was statistically significant, despite the small number of subjects. Adjusting the model for potential confounders such as age, race, LBM, serum insulin, and total and trunk fat did not significantly change the results. in vitro study found differing levels of leptin mRNA in subcutaneous versus intra-abdominal fat [Studies in HIV-negative individuals have shown differing relationships between circulating leptin and BMD in men and women. Reports in women have consistently found a positive association between leptin and BMD , 7, whilinal fat . This study has a number of limitations. First, we were able to assess only whole body BMD and BMC and did not have direct regional measurements of BMD in the spine or hip. Second, it is a cross-sectional study and our findings are associative in nature. Furthermore, the data used in this study are from the early HAART era, and although antiretroviral medications were not identified as potential confounders in our analyses, we have limited information regarding the duration of medication exposure. Despite the fact that current antiretroviral regimens differ from those in this study, we believe that our findings provide insight regarding the relationship between leptin and bone density. The strengths of our study include the uniformity of gender and study measurements and the ability to objectively measure body fat distribution using whole body DEXA scans in a population with a wide range of body sizes and total and regional fat content. Lastly, the study was performed prior to the widespread use of tenofovir, thereby eliminating the confounding effects of this medication on bone density.In summary, this study further extends our knowledge by suggesting a role for not just total fat but also fat distribution in explaining the relationship between serum leptin concentrations and bone density. We found that peripheral fat modified the relationship between bone density and leptin levels in HIV-infected men. Specifically, an inverse association between bone density and leptin levels was observed only in subjects with low amounts of peripheral fat. Further studies are required to confirm our findings and further clarify the relationship between fat distribution, bone density and circulating leptin concentrations.


There were also significant changes in phenylalanine catabolism marked by increases in phenylpyruvate  and phenyllactate  in EOC. Ovarian cancer also displayed an enhanced oxidative stress response as indicated by increases in 2-aminobutyrate in EOC  and in MOC  and several isoforms of tocopherols. We have also identified novel metabolites in the ovary, specifically N-acetylasparate and N-acetyl-aspartyl-glutamate, whose role in ovarian physiology has yet to be determined. These data enhance our understanding of the diverse biochemistry of the human ovary and demonstrate metabolic alterations upon transformation. Furthermore, metabolites with significant changes between groups provide insight into biochemical consequences of transformation and are candidate biomarkers of ovarian oncogenesis. Validation studies are warranted to determine whether these compounds have clinical utility in the diagnosis or clinical management of ovarian cancer patients.In this study, we characterized the metabolome of the human ovary and identified metabolic alternations that coincide with primary epithelial ovarian cancer (EOC) and metastatic tumors resulting from primary ovarian cancer (MOC) using three analytical platforms: gas chromatography mass spectrometry (GC/MS) and liquid chromatography tandem mass spectrometry (LC/MS/MS) using buffer systems and instrument settings to catalog positive or negative ions. The human ovarian metabolome was found to contain 364 biochemicals and upon transformation of the ovary caused changes in energy utilization, altering metabolites associated with glycolysis and β-oxidation of fatty acids—such as carnitine (1.79 fold in EOC,  It is estimated that 21,880 women will be diagnosed and 13,850 will die from this disease this year. The five-year survival rate at Stage I is 93.5% but drops to 27.6% at Stage IV, where a majority of cases are diagnosed due to a lack of symptoms at the earlier stages Ovarian cancer is the most lethal malignancy of the female reproductive system and the 5One approach to identify disease biomarkers is to use information-rich analytical tools such as omics-scale biological methods to characterize the composition of the target tissue in health and disease. In this case, it is important to understand the biochemical alterations that are known to occur during neoplastic transformation. The first energy metabolism alteration in cancer cells was described by Otto Warburg, who showed cancer cells preference for glycolysis resulting in the generation of lactate for ATP production over the more efficient process of oxidative phosphorylation by the mitochondria et al.The molecular mechanisms involved in the hyperactive glycolysis have been analyzed and some of key factors identified—including Akt, nuclear factor-κB (NF-κB), hypoxia-inducible factor-1 (HIF1), and p53 However, oncogenesis can result in a diverse panel of metabolic alterations that could be tissue specific or generic across human cancers. Therefore, a comprehensive metabolic analysis of solid tumors could reveal valuable metabolites for both early diagnosis of cancer as well as to monitor disease progression and/or recurrence to inform clinical management of cancer patients. These biomarkers could conceivably be used as surrogate endpoints in clinical trials and could suggest new metabolic targets for cancer management as well as provide complementary targets for chemotherapy treatment. Metabolomics is a systematic analytical tool used for identification of biochemical metabolites from cellular processes, a term that includes several types of analyses ranging for nuclear magnetic resonance spectroscopy (NMR), mass spectrometry (MS), tracer-based studies, and metabolic footprinting et al.et al.et al.In a previous study, Denkert Prior to this study, however, the metabolome of the normal ovary has not been studied, nor the changes that occur with neoplastic transformation and metastatic disease progression. In the present study, for the first time we report the metabolic profile of the normal human ovary and compare it to the metabolic profile of primary epithelial ovarian cancer (EOC) and metastatic tumors resulting from initial EOC (MOC) using GC/MS and LC/MS/MS.m/z), preferred adducts, and fragmentation pattern of the molecule. The comprehensive library allowed for rapid identification with a high fidelity. These compounds included a large variety of classes, ranging from simple amino acids and peptides to carbohydrates, lipids, nucleotides, cofactors and vitamins, and xenobiotics , 364 molecules were identified  when comobiotics .p≤0.05 in at least one of the pairwise comparisons . The identities of these metabolites are given in Data is a summation of individuals belonging to a group. Using one-way ANOVA with a Tukey post-test to identify differentially abundant metabolites across the three classes of tissue analyzed, 95 biochemicals were statistically significant and furthermore had a Using Ingenuity Pathway Analysis (IPA), we identified the top 15 canonical pathways involved in EOC  and MOC p<0.001 in EOC; −2.18 fold, p<0.001 in MOC), taurine , phenol sulfate , and 6-phosphogluconate , while the second principal component identified a further set of biochemical alterations that corresponded with metastasis . EvaluatMethylimidazoleacetate is the main metabolite of histamine. This end product of histamine catabolism is formed by N-methylation in the imidazole ring to methylhistamine by histamine methyltransferase and a subsequent oxidative deamination in the side chain by type B monoamine oxidase. From studies it is known that as much as 70–80% of the histamine metabolized in the body is excreted in the urine as methylimidazoleacetate Taurine is not involved in protein synthesis and/or has limited participation in biochemical pathways outside of peroxisomal formation of N-acyl lipid conjugates, such as bile acids and fatty acids. However, several functions have been demonstrated for taurine—such as osmoregulation, membrane stabilization, detoxification, antioxidation, modulation of ion flux, and as an inhibitory neurotransmitter or neuromodulator Phenol sulfate is a hepatically processed gut microfloral metabolite, and 6-phosphogluconate is an intermediate in the utilization of glucose within the pentose phosphate pathway, potentially signifying that glucose is restricted from entry into the pentose phosphate pathway in the healthy ovary and that upon transformation there is a higher affinity mechanism in place for this mechanism. This interpretation makes sense given that the pentose phosphate pathway produces both ribose for nucleotide biosynthesis, as well as two molar equivalents of NAD(P)H that could mitigate oxidative stress and aid in glutathione recycling.Six compounds differentiated transformed ovarian tissue independent of whether the cancer was localized or metastatic . These compounds included several quaternary amines , the TCA cycle intermediates malate and fumarate and N-acetylglycine. Increased tissue quaternary amine concentrations are typically due to tissue demand for either choline or carnitine as the transporters for quaternary amines are selective but not specific p<0.001) and 1.37 (p = 0.0076), respectively, when compared to normal ovarian tissue. Only MOC showed an increase in glucose-6-phosphate . There were no significant changes in glucose, pyruvate, acetylphosphate, phosphate, pyrophosphate, or citrate between groups . This finding may be due to a loss of function of specific ovarian glycosylation pathways since it has been demonstrated that normal ovarian tissue expresses a specific protein fucosylation pathway that results in the fucose moiety being directly coupled to the protein through Ser/Thr The other carbohydrate with a significant increase in abundance in transformed ovarian tissue was fucose , acetylcarnitine , butyrylcarnitine , and propionylcarnitine increased 5.7 fold (p = 0.0047) in MOC only  was upregulated 8.63 fold (p = 0.0056) in MOC compared to normal . In addip = 0.0114 in EOC; Interestingly, we also found that the recently described oncometabolite, 2-hydroxyglutarate had increased abundance in EOC  in EOC only compared to normal but decreased −3.68 fold (p = 0.036) in MOC compared to EOC. Phenyllactate (PLA) increased 195.45 fold (p<0.0023) in EOC, a finding which is typically attributed to insufficient activity of phenylalanine hydroxylase p = 0.0203) in EOC compared to normal only, whereas 4-hydroxyphenylpyruvate was increased 17.82 fold (p = 0.0069) in EOC compared to normal. Phenylalanine, tyrosine, phenylacetylglutamine, and 4-hydroxyphenylacetate were not significantly changed. Phenylalanine and its major metabolites—phenylpyruvate, PLA, and phenylacetate—induce oxidative stress in the hippocampus and cerebral cortrex via generation of reactive oxygen species, which was mitigated by α-tocopherol Phenylalanine catabolism also results in the production of ketones, namely phenylpyruvate and 4-hydroxypyruvate. Major metabolites of phenylalanine catabolism were significantly increased in EOC compared to normal . Phenylpp<0.001) compared to normal and 627.67 fold (p = 0.0023) compared to EOC. δ-tocopherol increased 1,775.51 fold (p<0.001) compared to normal and 1,950.08 fold (p<0.001) compared to EOC. γ-tocopherol increased 95.74 fold (p<0.001) compared to normal and 83.79 fold (p<0.001) compared to EOC  with the thiol group of GSH replaced with a methyl group. Ophthalmate can be synthesized from 2-aminobutyrate and glutamate by the enzyme γ-glutamyl cysteine synthetase (GCS) to form γ-glutamyl-2-aminobutyrate p = 0.0316) and MOC , suggesting an enhanced oxidative response. Ophthalmate increased 2.94 fold in MOC , GSH, γ-glutamyl-2-aminobutyrate, and ophthalmate can be detected in the serum in mice 2+-dependent manner from nerve terminals p = 0.0301) and 2.19 (p = 0.0352), respectively, with further increases in MOC with a fold change of 85.60 fold (p<0.001) and 8.09 (p<0.001), respectively (N-acetylasparate (NAA) is a free amino acid found in the brain at very high concentrations that functions as an osmolyte in fluid balance to protect neurons against osmotic stress ectively .NAAG is broken down by N-acetylated alpha-linked acidic dipeptidase (NAALADase), a NAAG-specific catabolic enzyme Metabolomics has been widely used to identify biomarkers for various disease states—including diabetes et al.et al.et al.In this study, the comprehensive metabolic profile of normal ovaries, EOC, and MOC were compared using GC/MS or LC/MS/MS. Significant changes in energy utilization were detected as well as an enhanced oxidative stress response. Similar to the study by Denkert Additional metabolic analysis in colorectal tissue One of the proposed biomarkers for tumor progression and invasiveness in prostate cancer is sarcosine, also known as N-methylglycine Based on the data we have collected, we have identified possible candidates for biomarker analysis for both preliminary cancer diagnosis and metastatic disease progression. The dramatic increase of tocopherols in MOC makes these molecules attractive candidates for aggressiveness and/or progression. Further investigation is needed to determine the potential utility of these initial findings.For metabolic profiling, 30 patient tissues were obtained from University of Alabama, Birmingham, Comprehensive Cancer Center and stored at −80°C. Type and stage was determined by evaluation by a pathologist. Tissues included 12 normal ovarian samples (mean age 48.6±7.6 years), 11 primary ovarian adenocarcinomas ranging from Stage I through Stage IIIC (mean age 56.5±9.8 years), and 7 metastatic tumors in the omentum resulting from initial ovarian adenocarcinomas ranging from Stage IIIC through Stage IV (mean age 62±8.2 years). Patients with previous diseases and treatments were excluded from the study.100 µg of frozen biopsy tissue was submitted to Metabolon, Inc.  for sample extraction and analysis. In brief, Metabolon performed cold methanol extraction of mechanically disaggregated tissue samples and these extracts were split into three aliquots. The reproducibility of the extraction protocol was assessed by the recovery of xenobiotic compounds spiked into every tissue sample prior to extraction. These aliquots were processed and characterized by one of the three analytical methods previously described: UHPLC-ESI-MS/MS in the positive ion mode, UHPLC-ESI-MS/MS in the negative ion mode and sialylation followed by GC-EI-MS. Chromatographic timelines were standardized using a series of xenobiotics that elute at specified intervals throughout each chromatographic run. The technical variability of each analytical platform was assessed by repeated characterization of a pooled standard that contained an aliquot of each sample within the study. The platform for sample analysis has been described in detail Figure S1Supervised PCA separated normal ovarian tissue from ovarian cancer  and localized tumor from metastasis .(TIF)Click here for additional data file.Table S1List of metabolites identified through mass spectrometry.(XLS)Click here for additional data file.Table S2ANOVA analysis of metabolites grouped by class of compound.(XLS)Click here for additional data file.Table S3Ingenuity pathway analysis for the top 15 canonical pathways for EOC.(XLS)Click here for additional data file.Table S4Ingenuity pathway analysis for the top 15 canonical pathways for MOC.(XLS)Click here for additional data file.


It has been well documented that obesity is closely associated with metabolic syndrome (MetS). Although body mass index (BMI) is the most frequently used method to assess overweightness and obesity, this method has been criticized because BMI does not always reflect true body fatness, which may be better evaluated by assessment of body fat and fat-free mass. The objective of this study was to investigate the best indicator to predict the presence of MetS among fat mass index, BMI and percentage of body fat (BF %) and determine its optimal cut-off value in the screening of MetS in practice.A cross-sectional study of 1698 subjects (aged 20–79 years) who participated in the annual health check-ups was employed. Body composition was measured by bioelectrical impedance analysis (BIA). Fat mass index (FMI) was calculated. Sex-specific FMI quartiles were defined as follows: Q1: <4.39, Q2:4.39- < 5.65, Q3:5.65- < 7.03, Q4:≥7.03,in men; and Q1:<5.25, Q2:5.25- < 6.33, Q3:6.33- < 7.93,Q4:≥7.93, in women. MetS was defined by National Cholesterol Education Program/Adult Treatment Panel III criteria. The association between FMI quartiles and MetS was assessed using Binary logistic regression. Receiver operating curve(ROC) analysis was used to determine optimal cutoff points for BMI,BF% and FMI in relation to the area under the curve(AUC),sensitivity and specificity in men and women.P < 0.01) and 52.039(4.144-653.436) for women( P < 0.01) after adjusting age, BMI, BF%, TC, LDL, CRP, smoking status and exercise status, and the odds ratios were 9.166(2.157-38.952) for men( P < 0.01) and 25.574(1.945-336.228) for women( P < 0.05) when WC was also added into the adjustment. It was determined that BMI values of 27.45 and 23.85 kg/m2, BF% of 23.95% and 31.35% and FMI of 7.00 and 7.90 kg/m2 were the optimal cutoff values to predict the presence of MetS among men and women according to the ROC curve analysis. Among the indicators used to predict MetS, FMI was the index that showed the greatest area under the ROC curve in both sexes.The adjusted odds ratios (95% CI) for the presence of MetS in the highest FMI quartile versus lowest quartile were 79.143(21.243-294.852) for men( Higher FMI levels appear to be independently and positively associated with the presence of MetS regardless of BMI and BF%. FMI seems to be a better screening tool in prediction of the presence of metabolic syndrome than BMI and percentage of body fat in men and women. Obesity is one of basic clinical conditions of metabolic syndrome (MetS), which is a cluster of risk factors for cardiovascular disease (CVD). The clustering of factors includes overweight/obesity, hyperinsulinemia, hypertension, hyperlipidemia, fasting hyperglucose or type 2 diabetes mellitus, and obesity  plays a central role in the MetS . The groAlthough body mass index (BMI) is the most frequently used method to assess overweightness and obesity, this method has been criticized because BMI does not always reflect true body fatness -6 and ha2) and a fat mass index  that considers an individual’s height [Until now, bioelectrical impedance analysis (BIA) has been considered as the simplest, most reproducible and least expensive method for body composition evaluation in clinical practice, and it showed high accuracy and excellent correlation with dual-energy X-ray absorptiometry(DXA) in assessing BF% -17. Thers height . FMI ands height -24.The objective of this study was to investigate the best indicator to predict the presence of MetS among fat mass index, BMI and percentage of body fat (BF%) and determine its optimal cut-off value in the screening of MetS in practice.Subjects in the study were enrolled from 2179 people who participated in the annual health check-up in the Department of Medical examination center, Peking Union Medical College Hospital, China Academic Medical Science and Peking Union Medical College, China, in 2011(from January to July). A standard questionnaire was used by trained physicians to collect related information including age, sex, physical activity, smoking, and medication use, and then routine physical examinations were performed to all subjects, and two blood pressure recordings were obtained from the right arm of subjects in a sitting position after 30 min of rest; Diabetes or hypertension were recorded if a participant gave a positive answer to the question: Have you ever been diagnosed by a physician as diabetes or hypertension? Smoking status was categorized as current smokers and non-smokers (nonsmokers or stop smoking for at least 6 months). People who exercised three or more times a week for >30 minutes were categorized as the regular exercise group, and those who exercised less than three times a week were considered the non-regular group. The exclusion criteria were as the follows: 1) with the evidence of cancer, renal, or hematological disease; 2) a medication history of corticosteroids in the previous 6 months; 3) those who were going on a weight-loss program or weight loss ≥5% of body weight within 12 months; 4) people who refused to participate in this study.Finally, 1698 subjects aged 20 ~ 79 years were enrolled in the study (1105 men and 593 women). All of the study procedures were approved by the Ethics Committee of Peking Union Medical College Hospital, China Academic Medical Science. All subjects provided informed consent to participate in the study.2). Waist circumference measurements were taken at the end of normal expiration to the nearest 0.1 cm, measuring from the midway between the lower borders of the rib cage and the iliac crest.Anthropometric measurements of individuals wearing light clothing and without shoes were conducted by well-trained examiners. Height was measured to the nearest 0.1 cm with a portable stadiometer. Weight was measured in an upright position to the nearest 0.1 kg with a calibrated scale. Body mass index was calculated by dividing weight (kg) by height squared . Four electrodes were placed on the palm and thumb of both hands, and four on the anterior and posterior aspects of the soles of both feet. Then fat mass index was calculated by dividing the each subject’s fat mass (kg) by square of his/her height (m). FMI levels were divided into separate quartiles for men and women. Sex-specific FMI quartiles were used as follows: Q1: <4.39, Q2: 4.39- < 5.65, Q3: 5.65- < 7.03, Q4: ≥7.03, in men; and Q1: <5.25, Q2: 5.25- < 6.33, Q3: 6.33- < 7.93, Q4: ≥7.93, in women.Blood sample were collected from the subjects’ peripheral vein in the morning after a fasting period of 10–12 h. the samples were immediately centrifuged at 4°C, and plasma for assays of lipid profile , triglyceride (TG), low-density-lipoprotein cholesterol (LDL-C), and high-density-lipoprotein cholesterol (HDL-C)), fasting blood glucose (FBG), C-reactive protein (CRP), using an automated analyzer .2, and BMI ≥28 kg/m2 respectively, according to the cut-off point [The MetS was defined using the updated National Cholesterol Education Program/Adult Treatment Panel III criteria (NCEP-ATP III)  for Asiaff point  for ChinX2 test for categorical variables, respectively. The association between the sex-specific fat mass index quartile and metabolic syndrome were tested using Binary Logistic regression analysis, and we calculated the unadjusted and adjusted odds ratio (ORs) using the lowest quartile as the reference. Receiver operating curve (ROC) analysis were used to determine optimal cutoff points for BMI, FMI and BF% in relation to the area under the curve (AUC), sensitivity and specificity in men and women. The values of FMI, BMI and BF% that resulted in maximizing the Youden index (sensitivity + specificity-1) were defined as optimal. P < 0.05 was considered significant for all the statistical analysis.Statistical analysis were performed separately according to sex by using the Statistical Package for Social Science  continuous variables were expressed as means ± SD, whereas categorical variables were represented by frequency and percentage. The differences between two sexes and two groups (Mets group and non- Mets group) were examined by t-test for continuous variables and by P < 0.001), but the mean HDL, BF%, FMI, and the percentage of regular exerciser were significantly lower in men than in women (P < 0.001). No significant differences in the mean of age or SBP and in the prevalence of MetS were found between men and women.The characteristics of the 1698 participants are summarized in Table P < 0.001), but HDL was significantly lower than that in non- MetS group (P < 0.001). No significant differences in the mean of TC or the percentage of current smokers were found between MetS group and non- MetS group for both sexes. In addition, percentage of regular exercise (P = 0.008) and mean LDL (P = 0.007) in MetS group of men were significantly lower than in non- MetS group, and mean age in MetS group of women was higher than in non- MetS group (P < 0.001).In MetS group for both sexes Table , variablrd and 4th FMI quartiles for both men and women (P < 0.001 for both sexes) , whereas in women subjects, age, overall overweight or obesity, and elevated CRP level were independently associated with MetS . Odds ratio of MetS in both sexes were shown in Table According to Binary logistic regression analysis, besides high FMI level, overall overweight or obesity, and elevated CRP level, were independently associated with MetS in men , which indicates its best predictive potential among the the parameters.As shown in Figure Metabolic syndrome is associated with the development of diabetes, cardiovascular disease, which is the leading cause of mortality worldwide  and epidTo our best knowledge, this is the first large cross-sectional study that examined the association of fat mass index quartiles (by BIA) and metabolic syndrome and determine the optimal cut-off values of fat mass index in prediction of metabolic syndrome in practice in Chinese population.rd and 4th quartiles of FMI for men and the 4th quartile of FMI for women still had significantly higher Odds ratio for metabolic syndrome than the lowest quartile.In this study, BMI, BF% and FMI were used to screen the presence of metabolic syndrome. One study  conclude2 for men and 7.90 kg/m2 for women by BIA could effectively predict the presence of MetS in our study. A recent study [Therefore,our study shows that high FMI level appears to be independently associated with MetS regardless of BMI and BF% and can be the effective measurement method for the assessment of metabolic syndrome in clinical practice. FMI of 7.00 kg/mnt study  showed tnt study , was theIn addition, our study determined that the CRP level were significantly higher in postmenopausal women with MetS than those without MetS and higher CRP level is independent factor for the presence of metabolic syndrome, which is consistent with one recent study . In addiThis study has several limitations. First, due to the cross-sectional design, it is not possible to explore the causal relationship between body composition and metabolic syndrome. Second, our population is restricted to 20-79-year-old men and women living in Beijing,and the result from oue study might not be applicable to other population. Third, hypertriglyceridemia, Low HDL-c, fasting hyperglucemia did not be included in the regression analysis, because they are the essential criteria in the diagnosis for MetS. Fourth, the prevalence of metabolic syndrome with age group (particularly in women since the post-menopause status might contribute to the risk of MetS due to the excessive fat accumulation) was not mentioned in this article, and further investigation should be performed in the future studies.Despite these limitations, our study suggested that FMI seems to be a better indicator in the screening of the presence of metabolic syndrome than BMI and percentage of body fat in men and women.MetS: Metabolic syndrome; BMI: Body mass index; WC: Waist circumference; SBP: Systolic blood pressure; DBP: Diastolic blood pressure; TC: Total cholesterol; TG: Triglyceride; HDL-C: High-density-lipoprotein cholesterol; LDL-C: Low-density-lipoprotein cholesterol; FBG: Fasting blood glucose; CRP: C-reactive protein; BF%: Percentage of body fat; FMI: Fat mass index.The authors declare that they have no competing interests.MF was responsible for the study design. LPJ participated in the design of the study and drafted the manuscript. LHP participated in the sequence alignment. LYP performed the statistical analysis. All authors read and approved the final manuscript.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2458/13/629/prepub