Ultra-processed food consumption and the risk of pancreatic cancer in the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial.

Whether ultra-processed food consumption is associated with the risk of pancreatic cancer has not been determined. We performed a prospective study to fill this gap. A population-based cohort of 98 265 American adults was identified from the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. Ultra-processed foods were defined by the NOVA classification. Cox regression was used to estimate hazard ratios (HRs) for pancreatic cancer incidence. Subgroup analysis was performed to identify the potential effect modifiers. During a mean follow-up of 8.86 years, 387 pancreatic cancer cases occurred. High consumption of ultra-processed foods was found to be associated with an increased risk of pancreatic cancer (fully adjusted HRquartile 4 vs 1 :1.49; 95% confidence interval [CI]: 1.07-2.07; Ptrend  = .021) in a linear dose-response manner (Pnonlinearity  = .075). Subgroup analysis further found that the positive association of ultra-processed food consumption with the risk of pancreatic cancer was more pronounced in subjects aged <65 years (HRquartile 4 vs 1 :2.17; 95% CI: 1.14-4.15) than in those aged ≥65 years (HRquartile 4 vs 1 :1.32; 95% CI: 0.88-1.94), though the interaction test failed to achieve the statistical significance (Pinteraction  = .061). These findings suggest that reducing ultra-processed food consumption may be beneficial in decreasing pancreatic cancer incidence.

Biomarkers for Predicting the Occurrence and Progression of Atrial Fibrillation: Soluble Suppression of Tumorigenicity 2 Protein and Tissue Inhibitor of Matrix Metalloproteinase-1.

Background: Soluble suppression of tumorigenicity 2 protein (sST2) and tissue inhibitor of matrix metalloproteinase (TIMP)-1 are involved in multiple pathogenic pathways, including cardiac remodeling, which is the main pathology of atrial fibrillation (AF). This study aims to investigate the previously unexplored relationship between the serum levels of sST2, TIMP-1, and AF. Methods: This was a prospective cross-sectional study conducted at the Capital Medical University Affiliated Beijing Anzhen Hospital between June 2019 and July 2020, with a total of 359 participants. The clinical characteristics and laboratory results of the patients were compared, and multivariable ordinal logistic regression was used to evaluate the relationship between serum sST2, TIMP-1, and AF. Results: The participants included 110 patients with sinus rhythm (SR), 113 with paroxysmal AF (the paroxysmal AF group), and 136 with persistent AF (the persistent AF group). It was found that the sST2 levels gradually increased in these three groups, from 9.1 (6.7-12.4 pg/ml) in the SR group to 14.0 (10.4-20.8 pg/ml) in the paroxysmal AF group and to 19.0 (13.1-27.8) pg/ml) in the persistent AF group (p < 0.001). The multivariable ordinal logistic regression model for sST2 and TIMP-1 demonstrated that sST2 had an area under the receiver operating characteristic (ROC) curve (AUC) of 0.797 (95% confidence interval (CI) 0.749-0.846, p < 0.001) and TIMP-1 had an AUC of 0.795 (95% CI 0.750-0.841, p=0.000). The multivariable ordinal logistic regression model for sST2 and TIMP-1 showed good discrimination between SR and AF, with an AUC of 0.846, and the addition of clinical factors, such as brain natriuretic peptide (BNP), left atrial diameter, age, and gender, to the biomarker model improved the detection of SR and AF (AUC 0.901). Conclusions: In this cohort study, sST2 and TIMP-1 were associated with AF progression, independent of clinical characteristics and biomarkers. Soluble ST2 and TIMP-1 combined with age, elevated N-terminal-pro hormone BNP(NT-BNP), and an enlarged left atrium were able to demonstrate the progression of AF reliably.

Dietary Vitamin K Intake and the Risk of Pancreatic Cancer: A Prospective Study of 101,695 American Adults.

No epidemiologic studies have been conducted to assess the association of intake of dietary vitamin K with the risk of pancreatic cancer. We used prospective data from the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial between 1993 and 2009 to fill this gap. A total of 101,695 subjects were identified. Dietary intakes of phylloquinone (vitamin K1), menaquinones (vitamin K2), and dihydrophylloquinone (dihydrovitamin K1) were assessed using a food frequency questionnaire. Cox regression was applied to calculate hazard ratios and 95% confidence intervals. During a mean follow-up of 8.86 years (900,744.57 person-years), 361 cases of pancreatic cancer were documented. In the fully adjusted model, dietary intakes of phylloquinone (for quartile 4 vs. quartile 1, hazard ratio (HR) = 0.57, 95% confidence interval (CI): 0.39, 0.83; P for trend = 0.002) and dihydrophylloquinone (for quartile 4 vs. quartile 1, HR = 0.59; 95% CI: 0.41, 0.85; P for trend = 0.006), but not menaquinones (for quartile 4 vs. quartile 1, HR = 0.93; 95% CI: 0.65, 1.33; P for trend = 0.816), were found to be inversely associated with the risk of pancreatic cancer in a nonlinear dose-response manner (all P values for nonlinearity < 0.05), and this was not modified by predefined stratification factors and remained in sensitivity analyses. In conclusion, dietary intakes of phylloquinone and dihydrophylloquinone, but not menaquinones, confer a lower risk of pancreatic cancer. Future studies should confirm our findings.

Efficacy and cost-effectiveness of fecal immunochemical test versus colonoscopy in colorectal cancer screening: a systematic review and meta-analysis.

BACKGROUND AND AIMS: The fecal immunochemical test (FIT) and colonoscopy are the most commonly used strategies for colorectal cancer (CRC) screening worldwide. We aimed to compare their efficacy and cost-effectiveness in CRC screening in an average-risk population. METHODS: PubMed, Embase, and National Health Services Economic Evaluation Database were searched. Risk ratio (RR) was used to evaluate the differences in detection rates of colorectal neoplasia between FIT and colonoscopy groups. A random-effects model was used to pool RRs. Incremental cost-effectiveness ratios (ICERs) were calculated to evaluate the cost-effectiveness of FIT versus colonoscopy. RESULTS: Six randomized controlled trials and 17 cost-effectiveness studies were included. The participation rate in the FIT group was higher than that in the colonoscopy group (41.6% vs 21.9%). In the intention-to-treat analysis, FIT had a detection rate of CRC comparable with colonoscopy (RR, .73; 95% confidence interval, .37-1.42) and lower detection rates of any adenoma and advanced adenoma than 1-time colonoscopy. Most included cost-effectiveness studies showed that annual (13/15) or biennial (5/6) FIT was cost-saving (ICER < $0) or very cost-effective ($0 < ICER ≤ $25000/quality-adjusted life-year) compared with colonoscopy every 10 years. CONCLUSIONS: FIT may be similar to 1-time colonoscopy in the detection rate of CRC, although it has lower detection rates of any adenoma and advanced adenoma than 1-time colonoscopy. Furthermore, annual or biennial FIT appears to be very cost-effective or cost-saving compared with colonoscopy every 10 years. These findings indicate, at least partly, that FIT is noninferior to colonoscopy in CRC screening in an average-risk population. Our findings should be treated with caution and need to be further confirmed.

Long-term efficacy of implantable cardiac resynchronization therapy plus defibrillator for primary prevention of sudden cardiac death in patients with mild heart failure: an updated meta-analysis.

Previous studies of implantable cardiac resynchronization therapy plus defibrillator (CRT-D) therapy used for primary prevention of sudden cardiac death have suggested that CRT-D therapy is less effective in patients with mild heart failure and a wide QRS complex. However, the long-term benefits are variable. We performed a meta-analysis of randomized trials identified in systematic searches of MEDLINE, EMBASE, and the Cochrane Database. Three studies (3858 patients) with a mean follow-up of 66 months were included. Overall, CRT-D therapy was associated with significantly lower all-cause mortality than was implantable cardioverter defibrillator (ICD) therapy (OR, 0.78; 95 % CI, 0.63-0.96; P = 0.02; I (2) = 19 %). However, the risk of cardiac mortality was comparable between two groups (OR, 0.74; 95 % CI, 0.53-1.01; P = 0.06). CRT-D treatment was associated with a significantly lower risk of hospitalization for heart failure (OR, 0.67; 95 % CI, 0.50-0.89; P = 0.005; I (2) = 55 %). The composite outcome of all-cause mortality and hospitalization for heart failure was also markedly lower with CRT-D therapy than with ICD treatment alone (OR, 0.67; 95 % CI, 0.57-0.77; P < 0.0001; I (2) = 0 %). CRT-D therapy decreased the long-term risk of mortality and heart failure events in patients with mild heart failure with a wide QRS complex. However, long-term risk of cardiac mortality was similar between two groups. More randomized studies are needed to confirm these findings, especially in patients with NYHA class I heart failure or patients without LBBB.

Prediagnosis ultra-processed food consumption and prognosis of patients with colorectal, lung, prostate, or breast cancer: a large prospective multicenter study.

Background and aims: Whether ultra-processed food consumption is associated with cancer prognosis remains unknown. We aimed to test whether prediagnosis ultra-processed food consumption is positively associated with all-cause and cancer-specific mortality in patients with colorectal, lung, prostate, or breast cancer. Methods: This study included 1,100 colorectal cancer patients, 1750 lung cancer patients, 4,336 prostate cancer patients, and 2,443 breast cancer patients. Ultra-processed foods were assessed using the NOVA classification before the diagnosis of the first cancer. Multivariable Cox regression was used to calculate hazard ratio (HR) and 95% confidence interval (CI) for all-cause and cancer-specific mortality. Results: High ultra-processed food consumption before cancer diagnosis was significantly associated with an increased risk of all-cause mortality in lung (HRquartile 4 vs. 1: 1.18; 95% CI: 0.98, 1.40; Ptrend = 0.021) and prostate (HRquartile 4 vs. 1: 1.18; 95% CI: 1.00, 1.39; Ptrend = 0.017) cancer patients in a nonlinear dose-response manner (all Pnonlinearity < 0.05), whereas no significant results were found for other associations of interest. Subgroup analyses additionally revealed a significantly positive association with colorectal cancer-specific mortality among colorectal cancer patients in stages I and II but not among those in stages III and IV (Pinteraction = 0.006), and with prostate cancer-specific mortality among prostate cancer patients with body mass index <25 but not among those with body mass index ≥25 (Pinteraction = 0.001). Conclusion: Our study suggests that reducing ultra-processed food consumption before cancer diagnosis may improve the overall survival of patients with lung or prostate cancer, and the cancer-specific survival of certain subgroups of patients with colorectal or prostate cancer.

Clinical characteristics and acute complication of COVID-19 patients with diabetes: a multicenter, retrospective study in Southern China.

Aims: This study aims to describe the clinical characteristics, laboratory data and complications of hospitalized COVID-19 patients with type 2 diabetes mellitus (T2DM) since epidemic prevention and control optimization was adjusted in December 2022 in China. Methods: This retrospective multicenter study included 298 patients with confirmed type 2 diabetes mellitus with or without COVID-19. We collected data from the first wave of the pandemic in The Fifth Affiliated Hospital of Guangzhou Medical University, Loudi Central Hospital and The First People's Hospital of Xiangtan from December 1, 2022 to February 1, 2023. We extracted baseline data, clinical symptoms, acute complications, laboratory findings, treatment and outcome data of each patient from electronic medical records. Results: For among 298 hospitalized patients with type 2 diabetes, 136 (45.6%) were COVID-19 uninfected, and 162 (54.4%) were COVID-19 infected. We found that the incidence of cough, fatigue, fever, muscle soreness, sore throat, shortness of breath, hyposmia, hypogeusia and polyphagia (all p<0.01) were significantly higher in the exposure group. They showed higher levels of ketone (p=0.04), creatinine (p<0.01), blood potassium (p=0.01) and more diabetic ketoacidosis (p<0.01). Patients with COVID-19 less use of metformin (p<0.01), thiazolidinediones (p<0.01) and SGLT2 (p<0.01) compared with patients without COVID-19. Conclusion: COVID-19 patients with diabetes showed more severe respiratory and constitutional symptoms and an increased proportion of hyposmia and hypogeusia. Moreover, COVID-19 patients with diabetes have a higher incidence of acute complications, are more prone to worsening renal function, and are more cautious about the use of antidiabetic drugs.

Identification and characterization of genes related to the development of skeletal muscle in the Hainan black goat.

In total, 185 unigenes were identified from 380 clones of postnatal skeletal muscle of Hainan Black goats by suppression subtractive hybridization (SSH) technology. Most of the differentially expressed genes involved energy metabolism and muscle contraction. The expression of 19 genes was analyzed in the longissimus dorsi muscles of 2-, 6-, 12-, 24-month olds, and four gene expression patterns were found by hierarchical cluster analysis. Most genes in first expression pattern belonged to myofibrillar proteins and had higher expression levels at 2 months old; genes of the secondary expression pattern had higher expression levels at 12 months old; tropomyoain 1 (alpha) (TPM1) was classified into the third expression pattern, and its expression level showed decreases tendency as age increased. Tropomyoain 2 (beta) (TPM2) was classified into the third expression pattern, which had the opposite expression pattern against TPM1.

[The effects of insulin and gliclazide therapy on endoplasmic reticulum stress and insulin sensitivity in liver of type 2 diabetic rats].

OBJECTIVE: To investigate the effect of insulin and gliclazide therapy on endoplasmic reticulum (ER) stress and insulin sensitivity in the liver of type 2 diabetic rats. METHODS: A high fat diet plus a low-dose of streptozotocin was implemented to create a type 2 diabetic rats which were randomly divided into diabetes mellitus (DM) group, insulin treatment (INS) group and gliclazide treatment (GT) group; and healthy rats were as normal control group. Diabetic rats in INS and GT groups were given neutral protamine hagedorn (NPH) insulin and gliclazide respectively for 3 weeks. Protein expression levels of immunoglobulin binding protein (Bip), spliced X-box binding protein 1 (XBP-1s), phosphorylated c-Jun on serine 73 (p-c-Jun), phosphorylated insulin receptor substrate 1 on serine 307 (p-IRS-1), and glucose-6-phosphatase (G6Pase) in liver homogenate were detected by Western blotting. RESULTS: Compared with the normal rats, Bip and XBP-1s in the DM group were up-regulated (0.28 ± 0.07 vs 0.90 ± 0.10 for Bip; 0.41 ± 0.07 vs 0.95 ± 0.07 for XBP-1s; both P < 0.01); p-c-Jun (0.59 ± 0.18 vs 1.94 ± 0.03), p-IRS-1 (1.73 ± 0.18 vs 5.32 ± 0.22) and G6Pase(0.11 ± 0.01 vs 0.45 ± 0.01) were increased (all P values < 0.01). In the INS group, all of aforementioned changes were reversed (0.90 ± 0.10 vs 0.25 ± 0.04 for Bip; 0.95 ± 0.07 vs 0.47 ± 0.01 for XBP-1s; 1.94 ± 0.03 vs 0.50 ± 0.10 for p-c-Jun; 5.32 ± 0.22 vs 1.59 ± 0.32 for p-IRS-1; 0.45 ± 0.01 vs 0.15 ± 0.02 for G6Pase, all P values < 0.01). In the GT group, all of aforementioned changes were also attenuated (0.90 ± 0.10 vs 0.53 ± 0.02 for Bip; 0.95 ± 0.07 vs 0.78 ± 0.02 for XBP-1s; 1.94 ± 0.03 vs 1.33 ± 0.11 for p-c-Jun; 5.32 ± 0.22 vs 3.13 ± 0.02 for p-IRS-1; 0.45 ± 0.01 vs 0.25 ± 0.01 for G6Pase, all P values < 0.05). Furthermore, all of aforementioned protein levels were down-regulated more obviously in the INS group comparing to the GT group (all P values < 0.01). CONCLUSIONS: Both insulin and gliclazide therapy could relieve ER stress and c-Jun N-terminal kinase activity and improved insulin sensitivity. The effect of insulin on Bip, XBP-1s, p-c-Jun, p-IRS-1 and G6Pase protein expressions is more obvious than that of gliclazide, which indicates besides lowering glucose, insulin might have protective effects of anti-inflammation, anti-oxidative stress or stimulation of lipid redistribution.

Egg consumption and risks of all-cause and cause-specific mortality: a dose-response meta-analysis of prospective cohort studies.

CONTEXT: Current dietary guidelines recommend eggs as a part of a healthy diet. However, whether egg consumption is associated with risk of mortality remains controversial. Moreover, the dose-response association of egg consumption with risk of mortality has not been determined. OBJECTIVE: To determine the potential dose-response association of egg consumption with risk of mortality in the general population. DATA SOURCES: The PubMed and Embase databases were searched for publications meeting eligibility criteria through November 2021. DATA EXTRACTION: Required data were extracted by 1 reviewer and then checked for accuracy by another reviewer. A random-effects dose-response meta-regression model was used to calculate the pooled risk estimates. A restricted cubic spline model was used to test nonlinearity. The certainty of evidence was assessed using the GRADE system. DATA ANALYSIS: Nineteen prospective cohort studies, involving 1 737 893 participants, were included. The pooled hazard ratios for an increase of 1 egg/d were 1.08 (95%CI, 1.01-1.15) for all-cause mortality, 1.07 (95%CI, 0.97-1.18) for cardiovascular disease-caused mortality, and 1.16 (95%CI, 1.04-1.30) for cancer-caused mortality. The certainty of evidence for these observations was rated as very low. Nonlinear dose-response associations were found for egg consumption and all-cause, cardiovascular disease-caused, and cancer-caused mortality. Moreover, the positive association between egg consumption and all-cause mortality was more pronounced in studies with adjustment for blood cholesterol-related covariates than those without (Pinteraction = 0.011). CONCLUSIONS: Greater amount of egg consumption confers higher risks of death from all causes, cardiovascular disease, and canc er in a nonlinear dose-response pattern. These findings should be treated with caution and need to be confirmed by future studies.

[Effects of early insulin therapy on sterol regulatory element binding protein 1 pathway and lipid accumulation in liver of type 2 diabetic rats].

OBJECTIVE: To explore the effect of early insulin therapy on sterol regulatory element binding protein 1 (SREBP1) pathway and lipid accumulation in liver of type 2 diabetic rats (DM). METHODS: A high-fat diet plus a low-dose of streptozotocin (STZ) was administered to the Sprague-Dawley (SD) rats to create a type 2 diabetic animal model. Then the rats were divided into 3 groups: normal control (NC), DM (untreated diabetic rats) and INS (a 3-week treatment of NPH insulin initiated from day 3 of STZ injection). Insulin was delivered daily by a 3-week subcutaneous injection (6 - 8 U/day). Liver homogenate was prepared. The protein levels of ER stress marker immunoglobulin binding protein (Bip), oxygen-regulated protein 150 (ORP150), insulin-induced gene 1 (Insig1), SREBP1 and nuclear SREBP1 (nSREBP1) were assayed by Western blot. Adipose tissue mass was measured. RESULTS: In the DM group, ER (endoplasmic reticulum) stress marker Bip and ORP150 were up-regulated (0.67 ± 0.02 vs 0.43 ± 0.01 for Bip; 1.11 ± 0.04 vs 1.83 ± 0.03 for ORP150, P < 0.05 for both) and Insig1 decreased (0.25 ± 0.02 vs 0.80 ± 0.07, P < 0.05). And the expressions of SREBP1 and nSREBP1 were elevated (1.03 ± 0.14 vs 0.41 ± 0.01 for SREBP1; 3.63 ± 0.77 vs 0.96 ± 0.20 for nSREBP1, P < 0.05 for both) in comparison with the normal control rats. In the INS group, all aforementioned changes became attenuated or reversed (0.41 ± 0.04 vs 0.67 ± 0.02 for Bip; 1.83 ± 0.03 vs 1.11 ± 0.04 for ORP150; 0.43 ± 0.02 vs 0.25 ± 0.02 for Insig1; 0.46 ± 0.01 vs 1.03 ± 0.14 for SREBP1; 1.65 ± 0.18 vs 3.63 ± 0.77 for nSREBP1, P < 0.05 for all). Furthermore, adipose tissue mass increased (22.4 g ± 3.6 g vs 12.0 g ± 2.6 g, P < 0.05). CONCLUSION: The early insulin therapy induces a fat redistribution from liver to adipose tissue. The mechanism is probably through a reduction of ER stress and a down-regulated pathway of SREBP1 in liver of diabetic rats.

Chocolate consumption and all-cause and cause-specific mortality in a US population: a post hoc analysis of the PLCO cancer screening trial.

Few studies with mixed results have examined the association between chocolate consumption and mortality. We aimed to examine this association in a US population. A population-based cohort of 91891 participants aged 55 to 74 years was identified. Chocolate consumption was assessed via a food frequency questionnaire. Cox regression was used to estimate risk estimates. After an average follow-up of 13.5 years, 19586 all-cause deaths were documented. Compared with no regular chocolate consumption, the maximally adjusted hazard ratios of all-cause mortality were 0.89 [95% confidence interval (CI) 0.84-0.94], 0.84 (95% CI 0.79-0.90), 0.86 (95% CI 0.81-0.93), and 0.87 (95% CI 0.82-0.93) for >0-0.5 servings/week, >0.5-1 serving/week, >1-2 servings/week, and >2 servings/week, respectively (Ptrend = 0.009). A somewhat stronger inverse association was observed for mortality from cardiovascular disease and Alzheimer's disease. A nonlinear dose-response pattern was found for all-cause and cardiovascular mortality (all Pnonlinearity < 0.01), with the lowest risk observed at chocolate consumption of 0.7 servings/week and 0.6 servings/week, respectively. The favorable associations with all-cause and cardiovascular mortality were found to be more pronounced in never smokers than in current or former smokers (all Pinteraction < 0.05). In conclusion, chocolate consumption confers reduced risks of mortality from all causes, cardiovascular disease, and Alzheimer's disease in this US population.

Dietary Acid Load and the Risk of Pancreatic Cancer: A Prospective Cohort Study.

BACKGROUND: Modern Western diets are rich in acidogenic foods. Human and in vitro studies suggest a potential link between dietary acid load and cancer risk. However, no epidemiologic studies have investigated the association of dietary acid load with the risk of pancreatic cancer. Therefore, we conducted a prospective cohort study to fill this gap. METHODS: A population-based cohort of 95,708 American adults was identified. Potential renal acid load (PRAL) and net endogenous acid production (NEAP) were used to assess dietary acid load of each subject, with greater values indicating greater dietary acid load. Cox regression was used to estimate risk estimates for pancreatic cancer incidence. Predefined subgroup analysis was used to identify the potential effect modifiers. RESULTS: A total of 337 pancreatic cancer cases were observed during 848,534.0 person-years of follow-up. PRAL score was found to be positively associated with the risk of pancreatic cancer [fully adjusted HRquartile 4 vs. 1: 1.73; 95% confidence interval (95% CI), 1.21-2.48; P trend = 0.001] in a nonlinear dose-response pattern (P nonlinearity = 0.012). Subgroup analysis found that the positive association of PRAL score with the risk of pancreatic cancer was more pronounced in subjects aged <65 years than in those ≥65 years (P interaction = 0.018). Similar results were obtained for NEAP score. CONCLUSIONS: Higher dietary acid load is associated with a higher risk of pancreatic cancer. Future studies should validate our findings in other populations and settings. IMPACTS: This is the first epidemiologic study suggesting that reducing dietary acid load may be useful in primary prevention of pancreatic cancer.

Insulin therapy stimulates lipid synthesis and improves endocrine functions of adipocytes in dietary obese C57BL/6 mice.

AIM: To evaluate whether insulin intervention could affect the metabolic and endocrine functions of adipose tissue. METHODS: C57BL/6 mice were fed on a high-fat-diet for 12-16 weeks to induce insulin resistance. Insulin intervention was administered in the high-fat-diet mice for 4 weeks at 12 weeks (early insulin treatment) or 16 weeks (late insulin treatment). Intraperitoneal glucose tolerance tests were performed before and after insulin treatment. Expression levels of factors involved in the triglyceride synthesis and endocrine functions of adipose tissue including phosphoenolpyruvate carboxykinase (PEPCK-C), fatty acid synthase (FAS), aquaporin 7 (AQP7), adiponectin, visfatin, and interleukin-6 (IL-6) were determined by Western blot. RESULTS: In the obese mice, glucose tolerance was impaired; triglyceride content was increased in the liver tissue; protein expression of FAS and adiponectin was decreased; expression of visfatin was increased in adipose tissue. After 4-week insulin treatment, glucose tolerance was improved; triglyceride content was decreased in the liver and skeletal muscle; expression of PEPCK-C, FAS, and adiponectin was increased in the adipose tissue; IL-6 and AQP7 expression was reduced in the fat. Early insulin treatment had better effect in increasing the expression of FAS and PEPCK-C and decreasing the expression of IL-6. CONCLUSION: These results indicate that insulin can target adipocytes for improvement of insulin sensitivity through stimulating triglyceride synthesis and partly improving endocrine functions.

[Effect of early insulin therapy on nuclear factor-kappaB inflammatory pathway in liver of diabetic rat].

OBJECTIVE: To investigate the effect of early insulin therapy on NF-kappaB pathway and inflammatory cytokine responses in liver of diabetic rat. METHODS: NF-kappaB p65 DNA binding was assayed with ELISA-based assay kit, cytokine gene expressions were quantified with real-time PCR and phosphoenolpyruvate carboxykinase (PEPCK), NF-kappaB and inhibitor kappaB (IkappaBalpha) protein levels were assayed with Western blot. Results Compared with control, hepatic PEPCK protein level in the untreated diabetic rat increased by 40%. Early insulin and gliclazide treatment normalized PEPCK protein level. The abundance of IkappaBalpha protein was significantly decreased and nuclear NF-kappaB p65 DNA binding activity was increased in untreated diabetic rats. IkappaBalpha protein content increased and NF-kappaB p65 DNA binding decreased during early intervention treatment. mRNAs encoding IL-1beta and TNFalpha were increased, which were reduced to normal levels after insulin and gliclazide treatment. CONCLUSIONS: It is suggested that early insulin treatment inhibits NF-kappaB activity and inflammatory cytokine responses in liver that are involved in the amelioration of insulin resistance in diabetic rats. Such results might be due to indirect antiinflammatory effects of insulin thus relieving glucotoxicity and lipotoxicity in peripheral tissues.

[Agonist-induced down-regulation of hepatic glucocorticoid receptor via peroxisome proliferator-activated receptor in SD rats].

OBJECTIVE: It was reported that a negative feedback loop might exist between peroxisome proliferator-activated receptor alpha (PPARalpha) and glucocorticoid receptor (GR). However, it is unclear whether GR expression is regulated by PPARalpha activation. To further demonstrate this possibility, we conducted the present study to investigate the regulatory effects of the PPARalpha agonist fenofibrate on GR expression in Sprague-Dawley rats. METHODS: GR gene and protein expression levels were determined in liver, visceral and muscle tissues. Adrenal 11beta-hydroxylase (CYP11B1) expression was examined by RT-PCR and circulating corticosterone level was measured by RIA method. RESULTS: GR expression was reduced by fenofibrate in a time- and does-dependent manner. The GR mRNA in the three fenofibrate groups of rats were 55% (FE1), 54% (FE2) and 68% (FE3) lower than that of the control rats. The GR protein were 28%, 77% and 99% lower than the control. The inhibition was observed in liver, but not in fat and muscle. The corticosterone level in the blood was increased significantly by fenofibrate(the levels of corticosterone in control, FE1, FE2, FE3, MK886 groups were (393 +/- 23), (495 +/- 44), (516 +/- 18), (622 +/- 93), (382 +/- 37) ng/ml respectively. These effects of fenofibrate were abolished by PPARalpha inhibitor MK886, suggesting that fenofibrate activated through PPARalpha. CONCLUSION: A new molecular mechanism has been found for a negative feedback regulation of GR activity by PPARalpha in SD rats.

Circulating Hematopoietic Stem/Progenitor Cells are Associated with Coronary Stenoses in Patients with Coronary Heart Disease.

Inflammatory cells in atherosclerotic plaque exclusively originate from hematopoietic stem/progenitor cells (HSPCs). In this study, we investigated whether circulating HSPCs frequency related to coronary stenosis in patients with coronary heart disease (CHD). Coronary angiography was performed in 468 participants who were recruited at Cardiology Centre in LuHe Hospital from March 2016 to May 2017. Among these subjects, 344 underwent echocardiography. Mononuclear cells isolated from peripheral blood were stained with an antibody cocktail containing anti-human CD34, anti-human lineage, anti-human CD38, and anti-human CD45RA. Lineage-CD38-CD45RAdimCD34+HSPCs were quantified by flow cytometry. CHD was defined as coronary stenosis ≥50% and the extent of CHD was further categorised by coronary stenosis ≥70%. A p < 0.0031 was regarded statistically significant by the Bonferroni correction. Circulating HSPCs frequency was 1.8-fold higher in CHD patients than non-CHD participants (p = 0.047). Multivariate-adjusted logistic analysis demonstrated that HSPCs was the only marker that was associated with the odds ratio of having mild vs. severe coronary stenosis (2.08 (95% CI, 1.35-3.21), p = 0.0009). Left ventricular ejection fraction was inversely correlated with HSPCs frequency and CRP in CHD patients (p < 0.05 for both). In conclusion, HSPCs frequency in circulation is intimately related to coronary stenoses in CHD patients.

[Relationship between pulse wave velocity and the NYha classification of coronary insufficiency].

OBJECTIVE: To investigate the relationship between brachial-ankle pulse wave velocity (baPWV) and different stage of cardiac dysfunction. METHODS: 253 consecutive patients with coronary atherosclerotic heart disease were enrolled from August 2006 to February 2007. Patients were grouped according to the functional classification of New York Heart Association (NYHA). The baPWV was measured non-invasively with a VP1000 automated PWV/ABI analyzer (PWV/ABI, Colin CO. Ltd., Komaki, Japan). At the same time, BNP, EF, LAEDV and LVESV were measured in all the patients. RESULTS: Brachial-ankle PWV was significantly correlated with cardiac function classification of NYHA (r = 0. 444, P < 0.001), BNP( r = 0.394, < 0.001) and left ventricular end diastolic volume (r = - 0.130, P < 0.05). The under area of receiver operating charachateistic (ROC) curve was 73.9%. The ROC curve demonstrated that when the value of brachial-ankle PWV was equal to or larger than 1717 cm/s (> 1717 cm/s), the sensitivity of diagnosing mild cardiac dysfunction was 72.9% and specifity 61.8%. When its value was equal to or larger than 1900 cm/s (> or = 1900 cm/s), the sensitivity and specificity were 61.5% and 81.9% respectively. CONCLUSION: Brachial-ankle PWV is significantly correlated to the NYHA classification of heart failure and it may be a prospective index to diagnose early stage of cardiac dysfunction.

[Effects of early insulin therapy on nuclear factor kappaB pathway in skeletal muscle of diabetes: experiment with rats].

OBJECTIVE: To investigate the effect of early insulin therapy on the nuclear factor kappaB (NF-kappaB) pathway and inflammatory cytokine responses in skeletal muscle in type 2 diabetes mellitus (DM). METHODS: SD rats underwent intraperitoneal injection of streptozotocin to establish DM models and then divided into 5 groups: early un-treated group, early gliclazide treated group (receiving gliclazide since the third day after blood glucose increase for 3 weeks for 3 weeks), early insulin treated group (receiving insulin since the third day after blood glucose increase for 3 weeks for 3 weeks), late un-treated group, and late insulin treated group (receiving insulin since the fourth week after blood glucose increase for 3 weeks). By the end of treatment the rats were killed. Homogenate of skeletal muscle was made. The NF-kappaB P65 DNA binding was assayed by ELISA-based assay kit. Real time PCR was used to detect the mRNA expression levels of the gene of the cytokines: glucose transporter 4 (Glut4), inhibitor kappaB (IkappaBalpha), IL-1beta, IL-6, and tumor necrosis factor (TNF)-alpha. And Glut4 and IkappaBalpha protein expression levels were assayed by Western blotting. RESULTS: The Glut4 mRNA level in the skeletal muscle of the untreated DM rats decreased by 59% and the Glut4 protein level in the muscle cell membrane decreased by 69%. Insulin treatment and gliclazide treatment increased the Glut4 mRNA expression by 17% and 13% respectively, increased the Glut4 protein expression in cell membrane by 23% and 10% respectively, and decreased the Glut4 protein expression in the cytoplasm. In the DM rats the IkappaBalpha protein expression in the skeletal muscle was significantly lower (P < 0.05) and the NF-kappaB P65 DNA binding activity increased, and TNF-alpha, IL-1B, and IL-6 expression levels were up-regulated in comparison with the normal control group. Early treatment of insulin and gliclazide increased the IkappaBalpha protein expression, decreased the NF-kappaB P65 DNA binding activity and the TNF-alpha expression in the skeletal muscle. CONCLUSION: Early insulin treatment inhibits the NFkappaB activity and inflammatory cytokine responses in skeletal muscle that are involved in the amelioration of insulin resistance in type 2 DM. Such results may be due to indirect antiinflammatory effects of insulin relieving glucotoxicity and lipotoxicity in peripheral tissues.

Comparative Efficacy of Antihypertensive Agents in Salt-Sensitive Hypertensive Patients: A Network Meta-Analysis.

BACKGROUND: Salt-sensitive hypertension (SSH) is an intermediate inherited phenotype of essential hypertension as well as being an independent risk factor for cardiovascular disease. However, effective medications for the treatment of SSH have not been clarified. This study was to compare the efficacious of different classes of antihypertensive agents combined with salt intake on the reduction of blood pressure (BP) in patients with SSH. METHODS: We used sources as PubMed, EMBASE, Cochrane Library, Cochrane Central Register of Controlled Trials (CENTRAL), ClinicalTrials.gov, International Clinical Trials Registry Platform (ICTRP), CNKI, and WANFANG database from inception to November 2016. Studies that compared the efficacy of 2 or more antihypertensive agents or placebos in adult salt-sensitive hypertensive patients were included. The outcomes included variations in mean arterial blood pressure, systolic and diastolic blood pressure. RESULTS: Twenty-five studies were involved in this meta-analysis. A calcium channel blocker (CCB) with hydrochlorothiazide and moderate salt intake was significantly the most efficacious in comparison with placebo (standardized mean differences (SMD), 95% credibility intervals (CI): 26.66, 12.60 to 40.16), angiotensin receptor blockers (ARBs) (SMD, 95% CI: 22.94, 5.26 to 40.51), and the other interventions for patients with SSH and no concomitant diseases. For SSH patients who were obese, CCB with metformin and moderate salt intake would decrease blood pressure with 17.90 mm Hg. CONCLUSIONS: For SSH patients with no concomitant diseases, CCB combined with hydrochlorothiazide and moderate salt intake was optimal in reducing BP, while CCB combined with metformin and moderate salt intake was the most efficacious at reducing BP in SSH patients with coexisting obesity.