Effect of home cook interventions for salt reduction in China: cluster randomised controlled trial.

OBJECTIVE: To determine the effects of salt reduction interventions designed for home cooks and family members. DESIGN: Cluster randomised controlled trial. SETTING: Six provinces in northern, central, and southern China from 15 October 2018 to 30 December 2019. PARTICIPANTS: 60 communities from six provinces (10 communities from each province) were randomised; each community comprised 26 people (two people from each of 13 families). INTERVENTIONS: Participants in the intervention group received 12 month interventions, including supportive environment building for salt reduction, six education sessions on salt reduction, and salt intake monitoring by seven day weighed record of salt and salty condiments. The control group did not receive any of the interventions. MAIN OUTCOME MEASURE: Difference between the two groups in change in salt intake measured by 24 hour urinary sodium during the 12 month follow-up. RESULTS: 1576 participants (775 (49.2%) men; mean age 55.8 (standard deviation 10.8) years) from 788 families (one home cook and one other adult in each family) completed the baseline assessment. After baseline assessment, 30 communities with 786 participants were allocated to the intervention group and 30 communities with 790 participants to the control group. During the trial, 157 (10%) participants were lost to follow-up, and the remaining 706 participants in the intervention group and 713 participants in the control group completed the follow-up assessment. During the 12 month follow-up, the urinary sodium excretion decreased from 4368.7 (standard deviation 1880.3) mg per 24 hours to 3977.0 (1688.8) mg per 24 hours in the intervention group and from 4418.7 (1973.7) mg per 24 hours to 4330.9 (1859.8) mg per 24 hours in the control group. Compared with the control group, adjusted mixed linear model analysis showed that the 24 hour urinary sodium excretion in the intervention group was reduced by 336.8 (95% confidence interval 127.9 to 545.7) mg per 24 hours (P=0.002); the systolic and diastolic blood pressures were reduced by 2.0 (0.4 to 3.5) (P=0.01) and 1.1 (0.1 to 2.0) mm Hg (P=0.03), respectively; and the knowledge, attitude, and behaviours in the intervention group improved significantly. CONCLUSIONS: The community based salt reduction package targeting home cooks and family members was effective in lowering salt intake and blood pressure. This intervention has the potential to be widely applied in China and other countries where home cooking remains a major source of salt intake. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR1800016804.

Shenfu Administration Improves Cardiac Fibrosis in Rats With Myocardial Ischemia-Reperfusion Through Adenosine A2a Receptor Activation.

OBJECTIVE: Shenfu injection (SFI) is commonly used for cardiac dysfunction in China. Adenosine receptors have been reported to exert anti-fibrosis effects. The intent of this study was to evaluate that SFI attenuates cardiac fibrosis through activating of adenosine A2a receptor (A2aR) in rats with myocardial ischemia-reperfusion (MI/R). METHODS: Sprague Dawley male rats were randomly divided into five groups, nine rats in each group. Injections in all rat groups were carried out prior to reperfusion, and in the sham and MI/R groups, only vehicle was injected. Injections in the remaining group were as follows: 5 mL/kg in the SFI group; 15 mg/kg nicorandil in the A2R agonist group; and 5 mL/kg SFI plus 5 mg/kg MSX-3 in the SFI + A2aR antagonist group. Changes in cyclic adenosine monophosphate (cAMP) and the development of myocardial infarction and cardiac fibrosis were documented among the groups. Additionally, the levels of A2aR, collagen Ⅰ, collagen Ⅲ, fibronectin, and matrix metalloproteinase-9 (MMP-9) were measured. RESULTS: Following injection with SFI or nicorandil, the cAMP concentration, infarct area, and cardiac fibrosis induced by MI/R injury were significantly decreased (p < 0.05). Additionally, the levels of collagen Ⅰ, collagen Ⅲ, fibronectin, and MMP-9 were clearly suppressed by SFI or nicorandil when compared with the MI/R group (p<0.01). However, the protective effects of SFI were counteracted by MSX-3. A negative correlation between A2aR and collagen I and collagen III was found (p = 0.00). CONCLUSION: SFI activated the A2aR to reduce myocardial fibrosis caused by MI/R injury, which provided an underlying mechanism of action of SFI.

Effects of Shenfu injection on myocardial adenosine receptors in rats with myocardial ischemia-reperfusion postconditioning.

OBJECTIVE: Shenfu injection (SFI) has been reported to have a protection against myocardial ischemia-reperfusion (MI/R) injury. However, the changes of adenosine receptors in MI/R postconditioning when pretreated with SFI are unclear. METHODS: Forty-five rats were randomly divided into sham group (sham), MI/R postconditioning group (MI/R-post), low-dose SFI group (1 mL/kg), middle-dose SFI group (2.5 mL/kg), and high-dose SFI group (5 mL/kg). In SFI groups, SFI was intravenously injected before reperfusion, and rats were treated with ischemic postconditioning after ischemia for 30 min. After 24 h of reperfusion, the levels of Ca2+ and cAMP in blood platelets were analyzed. Myocardial infarct volume and myocardial pathology were observed. The levels of adenosine receptor subtypes A1, A2b, and A3 in myocardium were analyzed using immunohistochemistry and Western blot. The oxidative stress-related indicators were also observed. RESULTS: Compared with the MI/R-post group, SFI ameliorated the MI/R injury by decreasing the myocardial infarct area, oxidative stress, and concentration of Ca2+ and cAMP (p < 0.01). Pretreatment with SFI enhanced the expression of adenosine receptors A1 and A2b in a dose manner compared with the MI/R-post group. In contrast, the levels of adenosine receptor A3 were increased after MI/R postconditioning compared with the sham group, and its expression continued to increase with the increase of SFI. Furthermore, the oxidative stress reduced with the concentrations of SFI. CONCLUSION: These results demonstrated that pretreatment with SFI might regulate the expression of adenosine receptors to improve the MI/R postconditioning.

Long non-coding RNA MAFG-AS1 knockdown blocks malignant progression in breast cancer cells by inactivating JAK2/STAT3 signaling pathway via MAFG-AS1/miR-3196/TFAP2A axis.

BACKGROUND: Breast cancer is still a leading threat to women's lives. Long non-coding RNAs (lncRNA) associated with cancer progression are getting attention. The objective of this study was to investigate the role of lncRNA MAFG-antisense 1 (MAFG-AS1) and mechanisms of action in breast cancer. METHODS: The expression of MAFG-AS1, microRNA-3196 (miR-3196) and transcription factor AP-2 alpha (TFAP2A) was detected by quantitative real-time polymerase chain reaction (qRT-PCR). The cell proliferation was assessed by 3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2-H-tetrazolium bromide (MTT) assay. The number of colonies was observed through colony formation assay. The protein levels of Cyclin D1, Ki67, Bcl-2 associated X protein (Bax), B-cell lymphoma2 (Bcl-2), Hexokinase II (HK2), lactate dehydrogenase A (LDHA), TFAP2A, Janus kinase 2 (JAK2), phosphorylated-JAK2 (p-JAK2), signal transducer and activator of transcription 3 (STAT3), and phosphorylated-STAT3 were quantified by western blot. The cell apoptosis was monitored using flow cytometry. The glycolysis progression was evaluated according to glucose consumption and lactate production. The relationship between miR-3196 and MAFG-AS1 or TFAP2A was predicted by the online tool starBase and verified by the dual-luciferase reporter assay. The role of MAFG-AS1 in vivo was determined by the tumor formation assay in nude mice. RESULTS: MAFG-AS1 was highly expressed in tumor tissues and cells. MAFG-AS1 knockdown restrained proliferation, colony formation, and glycolysis but promoted apoptosis of breast cancer cells. MiR-3196 was a target of MAFG-AS1, and its inhibition reversed the role of MAFG-AS1 knockdown. TFAP2A was a target of miR-3196, and its overexpression abolished the effects of miR-3196 reintroduction. MAFG-AS1 knockdown suppressed the activity of the JAK2/STAT3 signaling pathway. Moreover, MAFG-AS1 knockdown reduced tumor growth in vivo. CONCLUSION: MAFG-AS1 knockdown attenuated breast cancer progression in vitro and in vivo through activation of the JAK2/STAT3 signaling pathway by the MAFG-AS1/miR-3196/TFAP2A regulatory axis.

Evaluations of Alkyl hydroperoxide reductase B cell antigen epitope as a potential epitope vaccine against Campylobacter jejuni.

OBJECTIVE: The present study aimed to screen and find alkyl hydroperoxide reductase (AhpC) B cell dominant epitope of Campylobacter jejuni (C. jejuni). MATERIALS AND METHODS: Bio-informatic algorithms were used to predict B cell epitopes of AhpC. The AhpC protein and chemically synthesized antigenic epitopes of C. jejuni were considered as antigens, and the AhpC antibody was used as the primary antibody, ELISA and dot blot were used to analyze and screen the dominant epitope. The specific IgG of mice serum and IL-4 in splenocyte culture supernatant were detected by ELISA. The protective efficacy was evaluated by animal disease index and tissue histopathological staining of the jejunum. RESULTS: Seven epitopes of AhpC were predicted, one epitope (AhpC4-16) was found to recognize the antibodies of AhpC and had strong antigenicity by ELISA and dot blot analysis. In epitope AhpC4-16 immunized mice, specific IgG of serum and IL-4 in splenocyte culture supernatant were significantly higher. The illness index decreased significantly, the protective rate was 66.67%. Histopathology displayed that the jejunum morphology was better than the control group. CONCLUSIONS: These findings suggested that epitope AhpC4-16 showed effective protective role against C. jejuni and is a candidate epitope of vaccine against this pathogen.

Phase evolution of conversion-type electrode for lithium ion batteries.

Batteries with conversion-type electrodes exhibit higher energy storage density but suffer much severer capacity fading than those with the intercalation-type electrodes. The capacity fading has been considered as the result of contact failure between the active material and the current collector, or the breakdown of solid electrolyte interphase layer. Here, using a combination of synchrotron X-ray absorption spectroscopy and in situ transmission electron microscopy, we investigate the capacity fading issue of conversion-type materials by studying phase evolution of iron oxide composited structure during later-stage cycles, which is found completely different from its initial lithiation. The accumulative internal passivation phase and the surface layer over cycling enforce a rate-limiting diffusion barrier for the electron transport, which is responsible for the capacity degradation and poor rate capability. This work directly links the performance with the microscopic phase evolution in cycled electrode materials and provides insights into designing conversion-type electrode materials for applications.

Core needle biopsy promotes lung metastasis of breast cancer: An experimental study.

Core needle biopsy (CNB) may be used to diagnose early-stage breast cancer, but it may increase the risk of distant metastasis of tumor cells. The aim of the present study was to explore the effect of CNB on the distant metastasis of breast cancer. A total of 30 BALB/c mice were divided into two groups, namely biopsy and non-biopsy groups. The biopsy-related lung metastasis model (biopsy group) was established by the inoculation in the mammary fat pad of the mouse breast cancer cell line 4T1 combined with CNB. Flow cytometry, quantitative polymerase chain reaction analysis, morphological analysis, as well as other techniques, were used to evaluate the biological behavior of the tumors in the mouse model. A stable and reliable lung metastasis model of breast cancer was successfully established. The number of metastatic lung nodules in the biopsy group was significantly higher compared with that in the non-biopsy group (P<0.05). Compared with the non-biopsy group, the mRNA expression of transforming growth factor (TGF)-ß1, SOX4 and Ezh2 in the biopsy group was significantly upregulated (P<0.05) and the number of natural killer (NK) cells detected by flow cytometry was increased, but the difference was not statistically significant (P>0.05). Therefore, CNB was found to promote the lung metastasis of breast cancer, and the underlying mechanism may be associated with epithelial-to-mesenchymal transition (EMT) mediated by the TGF-ß1 signaling pathway.

Copeptin level in the early prediction of cardiorenal syndrome in rats.

Copeptin (CPP) has been considered as a useful marker for prediction of prognosis in heart diseases. However, CPP has not been investigated sufficiently in cardiorenal syndrome (CRS). The present study aimed to investigate the value of CPP level in predicting CRS in rats with partial nephrectomy combined with myocardial infarction (SNX + MI). A total of 60 male Sprague-Dawley rats were used to establish the CRS model by partial nephrectomy combined with MI. The rats were randomly divided into blank control (CK), SNX, MI and CRS groups. Changes in serum and urine CPP concentrations, hemodynamics, blood pressure, and renal function were examined 1-5 weeks after modeling. The predictive values of CPP in the occurrence of CRS in rats were evaluated using receiver operating characteristic (ROC) curve. The results showed that serum CPP in the CRS group in 1-5 weeks and urine CPP in 3 weeks after modeling increased significantly compared with the CK group. Also, serum B-type natriuretic peptide (BNP) in 1 and 3 weeks and urine BNP in 4-5 weeks after modeling increased significantly. No correlation was found between serum or urine CPP, BNP and BUN levels 1 week after modeling in the CRS group. The ROC curve analysis showed that the area under the curve of CRS predicted by serum CPP at 1 week was 0.908 with 56.59 pg/ml as the cutoff point, and its diagnostic sensitivity and specificity were 87.5 and 80.0%, respectively. To conclude, SNX + MI may be used to establish CRS rat model with cardiac and renal damage. Serum CPP may serve as a specific biomarker for the early prediction of CRS.

Grape Seed Proanthocyanidin Extract Inhibits Human Esophageal Squamous Cancerous Cell Line ECA109 via the NF-κB Signaling Pathway.

Esophageal squamous cell carcinoma is the most common type of squamous cell carcinoma. Grape seed proanthocyanidin extract (GSPE) is considered to exhibit anticancer activity against several different types of cancer. We aimed to determine whether GSPE inhibited esophageal squamous cancerous cells and the possible involvement of NF-κB in this process. The human esophageal squamous cancer cell line ECA109 was treated with GSPE (0-80 µg/mL) and BAY11-7082 (10 µmol/L) for 12, 24, and 48 h. The MTT assay was used to determine cell proliferation; alterations in cell apoptosis were detected by flow cytometry; levels of inflammatory factors interleukin-6 and cyclooxygenase-2 and apoptotic proteins Bax/Bcl-2 were measured by ELISA; qRT-PCR and western blots were used to examine the activation of caspase-3 and NF-κB signaling. GSPE inhibited the proliferation of ECA109 cells and induced cellular apoptosis in a time- and dose-dependent manner. ELISA results showed that GSPE and BAY11-7082 reduced the secretion of inflammatory cytokines interleukin-6 and cyclooxygenase-2. The results of PCR and western blotting indicated that GSPE and BAY11-7082 activated caspase-3 and attenuated the activation of the NF-κB signaling pathway. GSPE induced apoptosis in ECA109 cells and inhibited ECA109 cell proliferation via a reduction in the secretion of inflammatory cytokines. This mechanism may be related to the attenuation of NF-κB activity and the sensitization of caspase-3.

Alleviation of Arsenic-Induced Pulmonary Oxidative Damage by GSPE as Shown during In vivo and In vitro Experiments.

A long-term exposure to arsenic may lead to lung damage due to oxidative stress. In this context, GSPE can play a major role as a strong antioxidant. Our study attempted to reveal the connection between arsenic-induced lung injury and the antagonistic effect of GSPE. For this purpose, BEAS-2B cells and Kunming mice were exposed to different dosages of As2O3 and GSPE. Oxidative stress indicators were detected both in vivo and in vitro. Cell survival rate and morphological changes in the lung tissue (H&E staining) were evaluated as well. It was exhibited that As2O3 increased oxidative stress both in vivo and in vitro and decreased cells viability. In contrast, higher cell survival rate was revealed in the group treated with arsenic plus GSPE after 24 h as compared to that in the arsenic group. GSPE effectively reduced oxidative stress levels, along with increasing antioxidant capacity. In vivo experiments in arsenic-exposed group showed alveolar septum to be significantly thickened with considerable capillary congestion and invasion by inflammatory cells. After the intervention with GSPE, there seemed to be a dramatic reversal of morphology with thinning of the alveolar septum, decrease in capillary congestion, and number of inflammatory cells. This had shown that GSPE can effectively reduce the levels of oxidative stress, induced by arsenic in mice lung tissue. Conversely, antioxidant enzymes or products were increased. The experiment proved that GSPE can protect the lungs from oxidative damage induced by arsenic, and it may also be used as an antagonist against arsenic injuries.

Clinical effect of preoperative high-dose atorvastatin against no-reflow after PCI.

The aim of the present study was to evaluate the use of preoperative high-dose atorvastatin to prevent the no-reflow phenomenon after percutaneous coronary intervention (PCI). A total of 138 patients with ST-segment elevation myocardial infarction, admitted from March 2014 to January 2015, were enrolled and randomly divided into 3 groups of 46 individuals each. The groups included a control group in which patients were not treated with atorvastatin before PCI; a conventional-dose atorvastatin treatment group in which patients received a single dose of 20 mg at bedtime one day prior to PCI; and a high-dose atorvastatin treatment group in which patients were treated with 40 mg divided in two doses the day before PCI. The treatment effects were assessed by re-examining the echocardiography, high-sensitivity C-reactive protein and brain natriuretic peptide (BNP) levels after the PCI. The follow-up examinations included determinations of ultrasound imaging indicators and the contact with patients was maintained for a whole year. The CTFC (frame), pro-BNP, CK-MB peak and WMSI levels of the patients in the high-dose treatment group were significantly lower than those in the conventional dose or the control group. Trombolysis in myocardial infarction ≤2 and myocardial blush grade ≤1 levels were significantly lower than those in the conventional dose group (P=0.01) or those in the control group (P=0.01), although the echocardiographic indicators of the three groups were not significantly different (P<0.05). Nevertheless, it was found that there were significantly fewer adverse cardiovascular events in the high-dose group (P<0.05 in both cases). During the follow-up period, thromboembolism and restenosis were most infrequent in the high-dose atorvastatin group. Based on our findings the oral administration of high-dose atorvastatin before bedtime, one day before the procedure, can effectively prevent no-reflow cases, reduce adverse events and improve the long-term prognosis for acute coronary syndrome patients after PCI.

The beneficial effects of postconditioning on no-reflow phenomenon after percutaneous coronary intervention in patients with ST-elevation acute myocardial infarction.

No-reflow phenomenon is a serious complication of percutaneous coronary intervention (PCI) which is closely related to the incidence of major adverse cardiovascular events. It has been demonstrated that Postconditioning (PostC) during primary PCI confers protection against ischemia-reperfusion injury and thus might reduce infarct size. However, whether PostC may exert its beneficial effects on acute myocardial infarction (AMI) patients by reducing no-reflow phenomenon is still unknown. Sixty two patients diagnosed with ST-elevation AMI were randomly assigned to study group (n = 32) or control group (n = 30). Blood samples were obtained and assayed for creatine kinase MB (CK-MB) and high-sensitive C-reactive protein (hs-CRP). Determinants of reflow, including final thrombolysis in myocardial infarction (TIMI) grade-3 flow, ST-segment resolution (STR), myocardial blush grades-3 (MBG-3) and corrected thrombolysis in myocardial infarction frame count (cTFC), were comparative between the two groups. Compared with control group, more patients in study group were identified as the final TIMI grade-3 flow (81.3 vs. 56.7%, P = 0.036), MBG-3 (23 vs. 14%, P = 0.043) and STR ≥50% (93.8 vs. 73.3%, P = 0.029), while patients in study group had less cTFC (28.5 ± 9.1 vs. 37.4 ± 12.4, P = 0.002) After PCI, study group was associated with lower levels of CK-MB (2,397.6 ± 470.2 vs. 2,159.9 ± 485.5, P = 0.028), Troponin-I (197.5 ± 32.5 vs. 154 ± 43.1, P = 0.041) and hs-CRP (5.5 ± 4.5 vs. 9.5 ± 5.2 mg/L, P = 0.019) in comparison with control group. Left ventricle ejection fraction was better in the study group than in the control group (55.1 ± 9.8 vs. 42.9 ± 10.7, P = 0.042). PostC could improve myocardial reperfusion in patients with ST-elevation AMI undergoing PCI by reducing no-reflow. However, due to the limited sample size, the results of our study should not be considered conclusive.

Association between local interleukin-6 levels and slow flow/microvascular dysfunction.

We aimed to investigate the association between local interleukin-6 (IL-6) levels at the infarct-related artery and the risk of slow flow/microvascular dysfunction after PCI in ST-elevation acute myocardial infarction (AMI) patients treated by successful primary PCI. 56 eligible ST-elevation AMI patients (34 male/22 female, mean age: 63.5 ± 10.3 years), undergoing successful primary PCI, were included in the current study. Blood samples were obtained from the extraction catheter placed distal to the lesion before PCI. Plasma IL-6 levels were determined by immunoassay method. Slow flow/microvascular dysfunction was observed in 21 patients (37.5%). Using multiple logistic regression analysis, local IL-6 levels (OR 1.592, CI 1.135-2.268; P = 0.007) were found to be a significant risk factor of slow flow/microvascular dysfunction together with diabetes mellitus (OR = 8.065, CI 1.244-52.632; P = 0.029) and thrombus score (OR = 12.500, CI 1.100-142.857; P = 0.042). Receiver operating characteristic (ROC) curve analysis revealed that local IL-6 (ROC area 0.824, OR 1.704, CI 1.274-2.281, P < 0.001; optimal threshold ≥11.3 pg/ml) had a predictive value of slow flow/microvascular dysfunction with sensitivity of 73% and specificity of 71%. Our study indicated that inflammatory response as presented by local IL-6 levels was associated with slow flow/microvascular dysfunction in patients with ST-elevation AMI after successful primary PCI.

Effect of administration route on the renal safety of contrast agents: a meta-analysis of randomized controlled trials.

BACKGROUND: The objective of this study was to examine the association between administration route and relative renal safety of contrast agents. METHODS: We searched all published articles indexed in Embase, Medline and the Cochrane Central Register of Controlled Trials, from January 1980 to November 2010, to identify relevant studies. Of the 1,047 initially identified studies, 11 randomized controlled trials (RCTs) including 2,210 patients with intra-arterial route and 7 RCTs including 919 patients with intravenous route were finally analyzed. RESULTS: With regard to intra-arterial route, our meta-analysis showed that iodixanol significantly decreased the risk of contrast-induced acute kidney injury (CI-AKI) when compared with a pool of low-osmolar contrast media (LOCM; risk ratio [RR] = 0.68; 95% confidence interval [95% CI], 0.50-0.92; Z=2.47; p=0.01), with no significant heterogeneity between individual studies (p=0.14, I2=32.4%). However, iodixanol was not associated with a reduction in CI-AKI compared with the LOCM pooled together (RR=0.75; 95% CI, 0.44-1.26; Z=1.10; p=0.27) with intravenous application, again with no significant heterogeneity between individual studies (p=0.40, I2=3.6%). CONCLUSIONS: Our meta-analysis suggests that administration route may affect the renal safety of contrast agents. Specifically, iodixanol may be a better choice for patients in the interventional cardiology setting.

Prognostic role of brachial reactivity in patients with ST myocardial infarction after percutaneous coronary intervention.

OBJECTIVE: We hypothesized that flow-mediated vasodilation (FMD) in the brachial artery as a noninvasive method is of value in providing further predictive insights in a cohort of patients with ST-segment elevation acute myocardial infarction (STEMI) after percutaneous coronary intervention (PCI). METHODS AND RESULTS: One hundred and one patients (62.43+/-9.06, 67 men) with STEMI, undergoing successful primary and rescue PCI, were included in this study. FMDs of all patients were determined using ultrasound after PCI. Patients were tracked for subsequent cardiovascular events. Twenty-nine patients had an event during 12.1+/-2.6 months of follow-up. Multivariate Cox proportional hazard analysis identified a diagnosis of diabetes [hazard ratio (HR): 2.934, 95% confidence interval (CI): 1.314-6.548, P=0.0086], ejection fraction (HR: 0.900, 95% CI: 0.832-0.973, P=0.0082), and FMD (HR: 0.705, 95% CI: 0.573-0.868, P=0.0010) after adjustment of all entered baseline variables. ROC analysis showed that FMD (ROC area: 0.689, P=0.0012; optimal threshold: 5.5% or less) had predictive value with sensitivity of 64%, specificity of 61%, positive predictive value of 40%, and negative predictive value of 81%. CONCLUSION: In patients with STEMI, early evaluation of endothelial function after PCI could help to shed light on the mechanisms that increase the risk of new events. FMD could be used as a surrogate marker of events.