Research Progress of Small Plant Peptides on the Regulation of Plant Growth, Development, and Abiotic Stress.

Small peptides in plants are typically characterized as being shorter than 120 amino acids, with their biologically active variants comprising fewer than 20 amino acids. These peptides are instrumental in regulating plant growth, development, and physiological processes, even at minimal concentrations. They play a critical role in long-distance signal transduction within plants and act as primary responders to a range of stress conditions, including salinity, alkalinity, drought, high temperatures, and cold. This review highlights the crucial roles of various small peptides in plant growth and development, plant resistance to abiotic stress, and their involvement in long-distance transport. Furthermore, it elaborates their roles in the regulation of plant hormone biosynthesis. Special emphasis is given to the functions and mechanisms of small peptides in plants responding to abiotic stress conditions, aiming to provide valuable insights for researchers working on the comprehensive study and practical application of small peptides.

An efficient LC-MS/MS method for simultaneous determination of four substances in the Hcy metabolism pathway.

Aim: This study aimed to develop and validate an efficient LC-MS/MS method for the simultaneous determination of Hcy, Cys, Met and 5-methyltetrahydrofolate in human serum and to apply this method to patients with coronary artery disease. Methodology and results: Serum samples were prepared by reduction with dithiothreitol followed by protein precipitation. The analytical run time was 2.2 min. The linearity was good in the range of 2-100 µmol/l-1 for Hcy and Met, 10-500 µmol/l-1 for Cys, and 1-50 ng/ml-1 for 5-methyltetrahydrofolate. Conclusion: An accurate and precise method that was rapid, robust and with high-throughput for the routine clinical monitoring of patients with coronary artery disease was developed.

Effectiveness of a non-physician community health-care provider-led intensive blood pressure intervention versus usual care on cardiovascular disease (CRHCP): an open-label, blinded-endpoint, cluster-randomised trial.

BACKGROUND: Effectiveness of a non-physician community health-care provider-led intensive blood pressure intervention on cardiovascular disease has not been established. We aimed to test the effectiveness of such an intervention compared with usual care on risk of cardiovascular disease and all-cause death among individuals with hypertension. METHODS: In this open-label, blinded-endpoint, cluster-randomised trial, we recruited individuals aged at least 40 years with an untreated systolic blood pressure of at least 140 mm Hg or a diastolic blood pressure of at least 90 mm Hg (≥130 mm Hg and ≥80 mm Hg for those at high risk for cardiovascular disease or if currently taking antihypertensive medication). We randomly assigned (1:1) 326 villages to a non-physician community health-care provider-led intervention or usual care, stratified by provinces, counties, and townships. In the intervention group, trained non-physician community health-care providers initiated and titrated antihypertensive medications according to a simple stepped-care protocol to achieve a systolic blood pressure goal of less than 130 mm Hg and diastolic blood pressure goal of less than 80 mm Hg with supervision from primary care physicians. They also delivered discounted or free antihypertensive medications and health coaching for patients. The primary effectiveness outcome was a composite outcome of myocardial infarction, stroke, heart failure requiring hospitalisation, and cardiovascular disease death during the 36-month follow-up in the study participants. Safety was assessed every 6 months. This trial is registered with ClinicalTrials.gov, NCT03527719. FINDINGS: Between May 8 and Nov 28, 2018, we enrolled 163 villages per group with 33 995 participants. Over 36 months, the net group difference in systolic blood pressure reduction was -23·1 mm Hg (95% CI -24·4 to -21·9; p<0·0001) and in diastolic blood pressure reduction, it was -9·9 mm Hg (-10·6 to -9·3; p<0·0001). Fewer patients in the intervention group than the usual care group had a primary outcome (1·62% vs 2·40% per year; hazard ratio [HR] 0·67, 95% CI 0·61-0·73; p<0·0001). Secondary outcomes were also reduced in the intervention group: myocardial infarction (HR 0·77, 95% CI 0·60-0·98; p=0·037), stroke (0·66, 0·60-0·73; p<0·0001), heart failure (0·58, 0·42-0·81; p=0·0016), cardiovascular disease death (0·70, 0·58-0·83; p<0·0001), and all-cause death (0·85, 0·76-0·95; p=0·0037). The risk reduction of the primary outcome was consistent across subgroups of age, sex, education, antihypertensive medication use, and baseline cardiovascular disease risk. Hypotension was higher in the intervention than in the usual care group (1·75% vs 0·89%; p<0·0001). INTERPRETATION: The non-physician community health-care provider-led intensive blood pressure intervention is effective in reducing cardiovascular disease and death. FUNDING: The Ministry of Science and Technology of China and the Science and Technology Program of Liaoning Province, China.

Optimization of Structural and Processing Parameters for Selective Laser Melting of Porous 316L Bone Scaffolds.

In the implantation of porous bone scaffolds, good mechanical properties of the scaffold are a prerequisite for the long-term functionality of the implanted scaffolds, which varies according to the structure and the forming process. In this study, the influence of the forming parameters and structure of the Selective Laser Melting (SLM) process on the mechanical properties of 316L stainless steel bone scaffolds was investigated using finite element simulation combined with experimental methods. The mechanism of the influence of the process parameters and structure on the mechanical properties of bone scaffolds was summarized using static compression finite element numerical simulations, compression experiments, hydrodynamic simulations, forming numerical simulations and SLM forming experiments. The results show that the magnitude of residual stress and the distribution of defects under different process parameters had a strong influence on the microstructure and properties of the scaffold, and the residual stress of the Body-Centered Cube (BCC) structure formed at an energy density of 41.7 J/mm3 was significantly reduced, with less surface spheroidization and fewer cracks on the melt pool surface. The smallest grain size of 321 nm was obtained at an energy density of 77.4 J/mm3, while in terms of mechanical properties, the optimization of the structure resulted in an 8.3% increase in yield strength and a reduction in stress concentration. The predictions of stress, deformation, and forming quality during construction with different process parameters, achieved using finite element analysis, are basically in agreement with the experimental results, indicating that the best process parameters for forming BCC structural supports were determined by using finite element simulation combined with experiments; moreover, the distribution and evolution of residual stresses and defects under different process parameters for constructing BCC structures were obtained.

A village doctor-led multifaceted intervention for blood pressure control in rural China: an open, cluster randomised trial.

BACKGROUND: The prevalence of uncontrolled hypertension is high and increasing in low-income and middle-income countries. We tested the effectiveness of a multifaceted intervention for blood pressure control in rural China led by village doctors (community health workers on the front line of primary health care). METHODS: In this open, cluster randomised trial (China Rural Hypertension Control Project), 326 villages that had a regular village doctor and participated in the China New Rural Cooperative Medical Scheme were randomly assigned (1:1) to either village doctor-led multifaceted intervention or enhanced usual care (control), with stratification by provinces, counties, and townships. We recruited individuals aged 40 years or older with an untreated blood pressure of 140/90 mm Hg or higher (≥130/80 mm Hg among those with a history of cardiovascular disease, diabetes, or chronic kidney disease) or a treated blood pressure of 130/80 mm Hg or higher. In the intervention group, trained village doctors initiated and titrated antihypertensive medications according to a standard protocol with supervision from primary care physicians. Village doctors also conducted health coaching on home blood pressure monitoring, lifestyle changes, and medication adherence. The primary outcome (reported here) was the proportion of patients with a blood pressure of less than 130/80 mm Hg at 18 months. The analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, NCT03527719, and is ongoing. FINDINGS: Between May 8 and November 28, 2018, we enrolled 33 995 individuals from 163 intervention and 163 control villages. At 18 months, 8865 (57·0%) of 15 414 patients in the intervention group and 2895 (19·9%) of 14 500 patients in the control group had a blood pressure of less than 130/80 mm Hg, with a group difference of 37·0% (95% CI 34·9 to 39·1%; p<0·0001). Mean systolic blood pressure decreased by -26·3 mm Hg (95% CI -27·1 to -25·4) from baseline to 18 months in the intervention group and by -11·8 mm Hg (-12·6 to -11·0) in the control group, with a group difference of -14·5 mm Hg (95% CI -15·7 to -13·3 mm Hg; p<0·0001). Mean diastolic blood pressure decreased by -14·6 mm Hg (-15·1 to -14·2) from baseline to 18 months in the intervention group and by -7·5 mm Hg (-7·9 to -7·2) in the control group, with a group difference of -7·1 mm Hg (-7·7 to -6·5 mm Hg; p<0·0001). No treatment-related serious adverse events were reported in either group. INTERPRETATION: Compared with enhanced usual care, village doctor-led intervention resulted in statistically significant improvements in blood pressure control among rural residents in China. This feasible, effective, and sustainable implementation strategy could be scaled up in rural China and other low-income and middle-income countries for hypertension control. FUNDING: Ministry of Science and Technology of China.

Incremental significance and sex discrepancies of neck circumference on the odds of ischaemic stroke: a multistage, population-based, cross-sectional study from Northeast China.

OBJECTIVES: Accumulated evidence suggests that neck circumference (NC) is associated with cardiometabolic risk factors. However, limited studies are available regarding the association between NC or height normalised NC (neck-to-height ratio (NHR)) and risk of ischaemic stroke (IS) in the Chinese population. Therefore, we aimed at examining the associations between NC or NHR and odds of IS and exploring the discrepancies between men and women. DESIGN: A multistage cluster cross-sectional study. SETTING: A population-based study carried out in Northeast China. METHODS: A cross-sectional study was undertaken in Northeast China between September 2017 and March 2019, involving 7236 men and 11 352 women, respectively. The median age of participants was 60.30 years, ranging from 40 to 97 years. The associations between NC or NHR and odds of IS were calculated using multiple logistic regression models. Dose-response relationships were depicted using restricted cubic spline functions. Reclassification analyses were carried out to determine the incremental significance of NC or NHR on the odds of IS. RESULTS: In women, NC and NHR were significantly associated with the odds of IS, independent of traditional risk factors and other anthropometric parameters for obesity. The highest quartile of NC and NHR had a 1.60 (95% CI 1.16 to 2.22)-and 1.72 (95% CI 1.23 to 2.41) times higher odds of IS compared with the lowest quartile. Furthermore, the odds of IS increased by 1.10 (95% CI 1.01 to 1.20) and 1.12 (95% CI 1.02 to 1.22) times per 1 SD increase in NC and NHR, respectively. Reclassification analyses showed that the proportion of correct classification increased by 11.5% (95% CI 2.2% to 20.7%) and 22.8% (95% CI 13.5% to 32.0%) after the addition of NC or NHR into established models, respectively. However, the findings could not be replicated in men. CONCLUSION: NC and NHR might be promising independent indicators for women IS. Their incremental value in the risk stratification of IS enables the individualised prevention of IS in women.

Establishment of reference intervals of homocysteine, cysteine, and methionine in apparently healthy Chinese adults.

BACKGROUND: It has been widely reported that the key biomarkers of homocysteine metabolic pathways have emerged as markers or independent risk factors for cardiovascular disease and many other diseases. To improve the accuracy of evaluation in China, we establish the reference intervals of serum homocysteine (Hcy), cysteine (Cys), and methionine (Met) in apparently healthy Chinese adults. METHODS: We examined 1553 subjects aged ≥20 years who underwent Hcy metabolic pathway tests, in the Chaoyang Central Hospital between January 2019 and December 2020. The serum Hcy, Cys, and Met levels were simultaneously determined by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Multiple regression analysis was performed to identify sources of variation. A nonparametric method was used to establish the reference intervals. RESULTS: Gender differences were observed in Hcy and Met, with higher levels in males. Reference intervals for males were 6.09-17.00 µmol/L (Hcy) and 19.31-33.68 µmol/L (Met); conversely, the reference intervals for females were 4.61-14.61 µmol/L (Hcy) and 16.16-30.35 µmol/L (Met). The serum Cys reference intervals were seen to be gender-independent, but age-dependent reference intervals were needed; those for Cys were 188.85-334.27 µmol/L, 200.48-340.66 µmol/L, and 216.03-349.67 µmol/L in <40, 40-50, and ≥50 years, respectively. CONCLUSIONS: By this study, the gender- or age-specific reference intervals of Hcy, Cys, and Met that were matched with the Chinese population were established, providing valuable references for clinical work and laboratory researches.

Sex difference in the correlation between carotid artery diameter and prevalence of stroke: Insights from a Chinese population.

BACKGROUND: The atherosclerotic process can cause compensatory enlargement of artery diameter. However, the association between common carotid artery (CCA) diameter and stroke remains unclear. METHODS: This cross-sectional study included 5668 participants ≥40 years of age residing in rural northeast China, in whom the inter-adventitial diameter of CCA was measured. The association between CCA diameter and stroke prevalence was explored using multivariate logistic regression and concentration-response relationship in females and males, respectively. RESULTS: CCA diameter (mm) was greater in stroke than in non-stroke populations in both males (7.73 versus [vs.] 7.49; P < 0.05) and females (7.69 vs. 7.13; P < 0.001). Among males, when dividing CCA diameters into quartiles, the second quartile (6.86-7.5 mm) had a 1.64 times higher risk for stroke than the bottom quartile (≤6.85 mm) (P < 0.05) in the adjusted model. In females, the top quartile (>7.95 mm) had a 2.08 (1.07-4.04) times higher risk than the bottom quartile (≤6.50 mm) (P < 0.01) (overall trend 1.19 [1.00-1.43]). Moreover, dose-response relationship confirmed correlations between CCA diameter and stroke in females (P < 0.05). The net reclassification index (NRI) and integrated discrimination index (IDI) confirmed the incremental value of CCA diameter in predicting probability of stroke in females (NRI 0.353 [95% confidence interval (CI) 0.198-0.497], P < 0.001; IDI 0.004 [95% CI 0.001-0.006], P < 0.01) and males (NRI 0.201 [95% CI 0.158-0.241], P < 0.001; IDI 0.005 [95% CI 0.001-0.009], P < 0.01). CONCLUSIONS: This study highlighted the incremental value of CCA diameter in optimizing risk classification and stroke prevention in a Chinese population.

Overview of Rapid Detection Methods for Salmonella in Foods: Progress and Challenges.

Salmonella contamination in food production and processing is a serious threat to consumer health. More and more rapid detection methods have been proposed to compensate for the inefficiency of traditional bacterial cultures to suppress the high prevalence of Salmonella more efficiently. The contamination of Salmonella in foods can be identified by recognition elements and screened using rapid detection methods with different measurable signals (optical, electrical, etc.). Therefore, the different signal transduction mechanisms and Salmonella recognition elements are the key of the sensitivity, accuracy and specificity for the rapid detection methods. In this review, the bioreceptors for Salmonella were firstly summarized and described, then the current promising Salmonella rapid detection methods in foodstuffs with different signal transduction were objectively summarized and evaluated. Moreover, the challenges faced by these methods in practical monitoring and the development prospect were also emphasized to shed light on a new perspective for the Salmonella rapid detection methods applications.

Epidemiological features of hypertension among ischemic survivors in Northeast China: insights from a population-based study, 2017-2019.

BACKGROUND: Hypertension remains the major modifiable risk factor of stroke recurrence. The study aimed to determine the up-to-date epidemiological features of hypertension among the survivors of ischemic stroke. METHODS: Our cross-sectional study included 18,796 adults aged ≥40 years and residing in northeast China. Ischemic stroke was diagnosed according to the World Health Organization's criteria, which requires the clinical record, computed tomography (CT) and/or magnetic resonance imaging (MRI) during the hospital stay. Hypertension was defined according to the Chinese hypertension guidelines (mean SBP ≥140 mmHg and/or mean DBP ≥90 mmHg, and/or self-reported use of anti-hypertensive medication in the past 2 weeks). RESULTS: Of the 986 survivors of ischemic stroke, 819 (83.1%) were identified with hypertension (535 were pre-stroke hypertension and 284 were post-stroke hypertension). Among hypertensive patients, the awareness and treatment rates were 76.8 and 66.7% respectively. Only 11.0% achieved an appropriate blood pressure (< 140 mmHg and < 90 mmHg) among those who took hypertensive medications. 16.8% of treated hypertensive patients received combination therapy, and calcium channel blockers were the most frequently used anti-hypertensive medication as monotherapy. The mean systolic blood pressure (SBP) and diastolic blood pressure (DBP) of the stroke population was 155.3 ± 22.9 mmHg and 89.2 ± 12.3 mmHg. Both SBP and DBP were higher in rural patients than in urban patients (158.5 ± 23.8 mmHg vs. 146.4 ± 17.5 mmHg and 90.3 ± 12.9 mmHg vs. 85.9 ± 10.1 mmHg, respectively; p < 0.001). The rates of stage 2 and above hypertension in the ischemic stroke population were 32.5 and 18.7%, and was significantly higher in rural areas than in urban areas. CONCLUSIONS: The prevalence of poorly-controlled hypertension and the high rates of blood pressures at stages 2 and above in patients with prior ischemic stroke demonstrated an alarming situation in northeast China.

Rosuvastatin corrects oxidative stress and inflammation induced by LPS to attenuate cardiac injury by inhibiting the NLRP3/TLR4 pathway.

Rosuvastatin has been found to possess antioxidant and anti-inflammatory properties. The aim of the current study was to evaluate whether rosuvastatin was effective in attenuating cardiac injury in lipopolysaccharide (LPS) - challenged mice and H9C2 cells and identify the underlying mechanisms, focusing on the nod-like receptor protein 3 (NLRP3)/toll-like receptor 4 (TLR4) pathway. Cardiac injury, cardiac function, apoptosis, oxidative stress, inflammatory response, and the NLRP3/TLR4 pathway were evaluated in both in vivo and in vitro studies. LPS-induced cardiomyocyte injury was markedly attenuated by rosuvastatin treatment, evidenced by increased cell proliferation of H9C2 cells, rescued cardiac function, and improved morphological changes in mice and reduced lactate dehydrogenase (LDH), creatine kinase MB fraction (CK-MB), and troponin I (cTnI) in serum. Apoptosis was clearly ameliorated in myocardial tissue and H9C2 cells co-treated with rosuvastatin. In addition, after LPS challenge, excessive oxidative stress was present, indicated by increases in malondialdehyde (MDA) content, NADPH activity, and reactive oxygen species (ROS) production and decreased superoxide dismutase (SOD) activity. Rosuvastatin improved all the indicators of oxidative stress, with an effect similar to that of N-acetylcysteine (NAC) (an ROS scavenger). Notably, LPS-exposed H9C2 cells and mice showed significant NLRP3 and TLR4/nuclear factor-κB (NF-κB) pathway activation and inflammatory responses. Administration of rosuvastatin reduced the increases in NLRP3, apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC), pro-caspase-1, TLR4, and p65 expression and decreased the tumor necrosis factor α (TNF-α), interleukin 1ß (IL-1ß), IL-18, and IL-6 contents, with an effect similar to that of MCC950 (an NLRP3 inhibitor). In conclusion, inhibition of the inflammatory response and oxidative stress contributes to cardioprotective effect of rosuvastatin against cardiac injury induced by LPS, and the effect of rosuvastatin was achieved through inactivation of the NF-κB/NLRP3 pathway.

High prevalence of stroke and uncontrolled associated risk factors are major public health challenges in rural northeast China: A population-based study.

BACKGROUND: Stroke has become a major burden and public health problem in rural China. We aimed to comprehensively assess the current status of stroke burden as well as the associated risk factors in rural northeast China. METHODS: This population-based, cross-sectional study was conducted in 10,926 adults (response rate 85.3%) aged ≥40 years residing in rural northeast China. A multistage cluster sampling method was used to select the representative sample. The prevalent stroke cases were considered as stroke survivors on 31 August 2017. Stroke was diagnosed according to the World Health Organization's recommendations and was classified as ischemic stroke and hemorrhagic stroke based on the results of computed tomography or magnetic resonance imaging. The status of related risk factors was also evaluated. RESULTS: Of the 10,926 participants, 731 were diagnosed with stroke (602 patients with ischemic stroke, 151 with hemorrhage stroke, and 22 with both ischemic stroke and hemorrhage stroke). The crude prevalence of overall stroke, ischemic stroke, and hemorrhage stroke was 6690.5, 5509.8, and 1382.0 per 100,000 people, respectively, and the age-standardized rate was 4903.8, 4041.7, and 990.9 per 100,000 people. Among the overall stroke population, 13.4% were living with consequences of stroke. Hypertension (86.7%), dyslipidemia (37.2%), and diabetes (24.5%) were highly prevalent in stroke participants. However, most of those comorbidities remained uncontrolled (93.7, 44.7, and 88.9%, respectively). CONCLUSION: The burden of stroke in rural northeast China was substantial, with a high prevalence of stroke, recurrence, and disabilities. Uncontrolled comorbidities will likely contribute to recurrence and worsening disabilities in the coming decades. Strategies of long-term management of stroke and related risk factors are urgently required in rural northeast China.

Epidemiology of atrial fibrillation in northeast China: a cross-sectional study, 2017-2019.

OBJECTIVE: To evaluate the epidemiology of atrial fibrillation (AF) in northeast China. METHODS: This cross-sectional survey using a multistage, stratified and cluster random sampling method was conducted in Liaoning Province between September 2017 and March 2019. A total of 18 796 participants (28.9% urban, 71.1% rural) aged ≥40 years were included. All participants completed a questionnaire and underwent a physical examination and ECG. AF was diagnosed according to history and ECG findings. RESULTS: The overall AF prevalence was 1.1%; it increased steeply with age. AF was more prevalent in men than in women (1.5% vs 0.9%, p<0.001); however, the difference between urban and rural areas was not significant (1.3% vs 1.1%, p=0.228). Among the AF population, the overall AF awareness rate was 52.6%, higher in women than in men (61.5% vs 44.1%, p=0.011); however, the difference between areas was not statistically significant (60.0% vs 49.0%, p=0.129). According to the CHA2DS-VASc score, almost all (90.2%, 194/215) of our subjects required oral anticoagulant (OAC) therapy; however, only 4.1% actually received it. Moreover, hypertension (66.5%), dyslipidaemia (32.6%) and diabetes (24.2%) were highly prevalent in patients with AF, but their control rates were unacceptably low (7.0%, 8.6% and 28.8%, respectively). CONCLUSIONS: The burden of AF in northeast China was substantial. Underuse of OAC therapy and uncontrolled comorbidities will likely contribute to the cardiovascular outcomes of patients with AF in the coming decades. Long-term management strategies for AF and related risk factors are required in northeast China.

Urban-Rural disparities in status of hypertension in northeast China: a population-based study, 2017-2019.

BACKGROUND: To investigate the status of hypertension and related risk factor disparities between urban and rural areas of northeast China. METHODS: A multi-stage, stratified, and cluster random sampling method was used to conduct the cross-sectional survey in Liaoning Province in 2017-2019. Finally, included 18,796 participants (28.9% urban, 71.1% rural) aged ≥40 years. The prevalence and control rate of hypertension were estimated based on Chinese hypertension guidelines and the 2017 American College of Cardiology/American Heart Association (ACC/AHA) guidelines. RESULTS: The mean age of the population was 60.4±9.9 years, and 61.0% were women. The overall prevalence of hypertension was 56.8%. Compared to urban areas, hypertension was more prevalent, but the awareness, treatment, and control rates were lower in rural areas (59.2 vs 50.2, 52.5% vs 47.0%, 46.9% vs 34.9%, and 11.4% vs 3.7%, P<0.001, respectively). Multivariate regression analysis identified that the lack of exercise (odds ratio (OR), 1.24; 95% confidence interval (CI), 1.10-1.38) in rural areas, whereas overweight/obesity (OR, 2.01; 95% CI, 1.79-2.27) and alcohol consumption (OR, 1.20; 95% CI, 1.01-1.41) in urban areas were specific risk factors for hypertension, besides common risk factors. Under the 2017 ACC/AHA guidelines, the prevalence of hypertension was 80.6% (urban 76.6%, rural 82.2%), increased 1.4-fold compared with the current Chinese guidelines, with increased rates of 27.9% in urban areas and 25.7% in rural areas. CONCLUSION: A highly diverse prevalence for hypertension was found between urban and rural areas in northeast China. Region-specific strategies targeting the prevention and management of hypertension should be highlighted.

Trends in status of hypertension in rural northeast China: results from two representative cross-sectional surveys, 2013-2018.

OBJECTIVE: To investigate the long-term natural trends in the status of hypertension in rural northeast China from 2013 to 2018. METHODS: Two successive cross-sectional surveys were conducted in Liaoning rural areas in 2013 and 2018, which included 10 753 and 10 926 participants aged at least 40 years from different villages, respectively. A multistage, stratified, and cluster random sampling method was used to ensure that the samples of the two studies were representative. Hypertension was defined as a mean SBP at least 140 mmHg or a mean DBP at least 90 mmHg, and/or self-reported use of antihypertensive medication within the past 2 weeks. The prevalence and control rate of hypertension were also estimated according to the 2017 American College of Cardiology/American Heart Association high blood pressure guideline. RESULTS: Overall, the age-standardized prevalence of hypertension increased from 52.3 to 53.6%, while the age-specified DBP level increased by 5.2% (82.4 vs. 86.7 mmHg) during the study period. However, the control rate unfortunately remained low (4.1 vs. 3.6%), despite unsatisfied awareness and treatment rates of hypertension in rural northeast China. Under the 2017 American College of Cardiology/American Heart Association guideline, the prevalence of hypertension increased from 73.9 to 79.1%; however, the control rate decreased sharply from 1.8 to 0.5% between 2013 and 2018. CONCLUSION: Despite the high prevalence of hypertension during the past 5 years, blood pressure levels increased significantly, especially the DBP level. Awareness, treatment, and control of hypertension remained unacceptably low. Therefore, strategies targeting the management of hypertension should be emphasized in rural northeast China.

Characterization of monocyte chemoattractant proteins and CC chemokine receptor 2 expression during atherogenesis in apolipoprotein E-null mice.

AIM: We aimed to investigate the expression of monocyte chemoattractant proteins (MCPs) and their cognate receptor CC chemokine receptor 2 (CCR2) in aortas of apolipoprotein E-null (apoE(-/-)) mice during atherogenesis as well as the possible transcription pathway involved in the early induction of MCP-1 in vascular smooth muscle cells (VSMCs) in vivo. METHODS: Atherosclerotic lesion development, aortic MCPs and CCR2 mRNA expression as well as the cellular localization of MCP-1, CCR2 and MCP-1 related transcription factors in atherosclerotic lesions were analyzed in apoE(-/-) mice fed a high fat and cholesterol diet. RESULTS: MCP-1 and CCR2 mRNA expression was significantly induced during early atherogenesis and peaked after 10 and 12 weeks of diet, respectively, whereas MCP-2 and MCP-3 mRNA expression elevated in the late phases of lesion development. Immunostaining revealed that early MCP-1 expression was localized to VSMCs and that, in advanced lesions, both neointimal VSMCs and intimal macrophages expressed high levels of MCP-1. During the early (0 and 4 weeks of diet) induction of MCP-1 in VSMCs, the regulatory activator protein-1 (AP-1) proteins c-Jun and c-Fos were highly expressed and observed within the VSMCs nuclei, whereas nuclear factor-κB (NF-κB) protein p65 was only observed within the nuclei of VSMCs after 4 weeks of diet. CCR2 was also identified on intimal macrophages, endothelial cells and VSMCs in advanced lesions. CONCLUSION: This study provides fundamental information on the expression kinetics of MCPs and CCR2 during atherogenesis and indicates that the earliest induction of MCP-1 in VSMCs of apoE(-/-)mice appears to correlate with AP-1 but not NF-κB regulatory pathways.

High dietary n-6/n-3 PUFA ratio promotes HDL cholesterol level, but does not suppress atherogenesis in apolipoprotein E-null mice 1.

AIM: Dietary fatty acids affect atherogenesis, which was presumed to be partly related to HDL cholesterol (HDL-C) metabolism. The major aim of the work was to analyze various ratios of n-6/n-3 PUFA diets on HDL-C metabolism in apolipoprotein E-null (apoE(-/-)) mice, which have similar symptoms to human type III familial hyperlipoproteinemia. METHODS: Two-month-old male apoE(-/-) mice were fed four types of n-6/n-3 PUFA diet (group 1, 1.28; group 2, 5.03; group 3, 9.98 and group 4, 68.26) and control diet, respectively, for 6 weeks. With respect to serum apolipoprotein (apo) A-I concentration, lecithin-cholesterol acyltransferase (LCAT) activity and mRNA abundance of genes involved in HDL-C metabolism in the liver were analyzed. RESULTS: Group 4 diet significantly increased the plasma HDL-C and apoA-I concentrations compared with other groups. LCAT activity in serum increased with decreased ratios of n-6/n-3 PUFA. As the dietary ratio of n-6/n-3 fatty acids increased, so did mRNA levels of hepatic apoA-I, scavenger receptor B class-1 (SR-B1), LCAT, ATP binding cassette transporter A1 (ABCA1), ABCG1 and liver X receptor alpha (LXRalpha). ApoA-II mRNA level, however, had a tendency to fall. Group 4 diet increased apoA-I and ABCA1 and decreased apoA-II transcriptional levels, whereas group 1 diet decreased mRNA levels of apoA-I, LCAT, SR-B1 and ABCG1. CONCLUSION: Our data indicated that a high ratio of n-6/n-3 PUFA increased the serum HDL-C level, but did not effectively suppress atherogenesis in apoE(-/-) mice. The elevated HDL-C level is possibly due to up-regulated hepatic apoA-I and ABCA1 with suppression of apoA-Ii expression.

Tumor necrosis factor-alpha deficiency retards early fatty-streak lesion by influencing the expression of inflammatory factors in apoE-null mice.

Tumor necrosis factor-alpha (TNF-alpha), a key inflammatory cytokine, plays an important role in atherosclerosis. However, its precise characters in primary stage of the disease remain unclear. To assess the influence of TNF-alpha on inflammatory factors in aorta and liver in apoE and TNF-alpha double mutant (AT) mice, a comparative study on early fatty-streak lesion, the mRNA level of target gene in aorta and liver of adolescent AT and apoE-null (apoE(-/-)) mice were achieved. The characteristics of expression of inflammatory factors, and early fatty-streak lesion relevance were analyzed. The plasma cytokines in 6-week-old AT and apoE(-/-) mice were also measured. Lipid accumulation in the intima of the aorta existed as early as 3 weeks of age in apoE(-/-) mice. Fatty-streak lesion was mild in AT mice but prominent in apoE(-/-) mice, at age of 6 weeks. Furthermore, most interesting findings indicate that mRNA levels of pro-atherosclerotic factors, i.e. IL-1beta, IFN-gamma, ICAM-1, VCAM-1, MCP-1, GM-CSF and NF-kappaB (p65) were significantly downregulated in AT mice. Whereas IL-2 and IkappaB-alpha were upregulated in aorta of AT mice versus those in apoE(-/-) mice (p<0.01) and the transcript levels of pro-inflammatory cytokines, such as IL-1beta, IFN-gamma, ICAM-1, VCAM-1, MCP-1 and GM-CSF, increased with atherogenesis progression. On the other hand, the expression of these inflammatory factors in the liver displayed somewhat similar fashion to those in the aorta. Moreover, the plasma lipids profile in AT mice showed less pro-atherogenic than that of apoE(-/-) mice. Our data indicated that TNF-alpha deficiency surely, although not completely, retards fatty-streak lesion formation due to downregulated expression of the pro-atherosclerotic inflammatory factors in the present circumstance.

Effects of high dietary fat and cholesterol on expression of PPAR alpha, LXR alpha, and their responsive genes in the liver of apoE and LDLR double deficient mice.

The significance of transcription factors PPAR alpha, LXR alpha, and their responsive/target genes for the pathogenesis of atherosclerosis in apolipoprotein E and low-density lipoprotein receptor double deficient (AL) mice fed with high fat and cholesterol (HF) diet were studied. C57BL/6J wild-type (WT) mice were used as control to the AL mice. Plasma lipid metabolites and morphological atherosclerotic lesions in aortic wall were determined. Semi- and real-time quantitative RT-PCR were used to measure gene expression patterns between AL mice and the controls, which were fed with HF or normal chow diet. The results showed that in AL mice fed with HF diet, plasma lipid levels, hepatic lipid accumulation, and atherogenesis together with upregulated PPAR alpha, LXR alpha, and their target genes, i.e., FAT, SCD1, FAS, Angptl3, and apoB100 significantly increased in a 12-week long feeding period. In contrast, apoAI, apoAIV, apoF, LPL, and SR-BI were decreased compared to chow-fed group. In WT mice, PPAR alpha, LXR alpha, FAS, Angpt13, CPT1, apoF, ACOX1, LPL, and SR-BI were increased with HF treatment, while apoAI and apoAIV were decreased markedly. The different changes of lipid metabolism-related genes between AL and WT mice, fed with HF diet or chow diet indicated that the mechanisms of dietary effects on gene mutant mice are different from those of intact WT mice. Since lipid metabolic system defected genetically in AL mice, we suggest that the changes of PPAR alpha, LXR alpha, and their target genes aggravated lipid metabolic disorder in the liver and further accelerated the development of atherosclerosis on a stress of HF diet feeding in AL mice.

Molecular cloning, characterization and expression analysis of natural resistance associated macrophage protein (Nramp) cDNA from turbot (Scophthalmus maximus).

Nramp (natural resistance associated macrophage protein) has been identified as one of the major candidate genes for controlling natural resistance and/or susceptibility to intracellular pathogens in vertebrates. However, few reports are available about the structure and function of Nramp in teleost. We have recently isolated the cDNA encoding Nramp from turbot (Scophthalmus maximus). The full-length cDNA of the Nramp is 2584 bp in length, including 69 bp 5' terminal UTR, 850 bp 3' terminal UTR and 1665 bp open reading frame for a protein with 554 amino acid residues (Genbank accession number: DQ263240). Comparison of amino acid sequence indicated that turbot Nramp consists of 12 transmembrane regions (TM) domains. A consensus transport motif (CTM) containing 20 residues was observed between transmembrane domains 8 and 9. The deduced amino acid sequence of turbot Nramp exhibited between 60 and 92% homology with 13 other vertebrate Nramp sequences. Nramp transcripts were found to be highly abundant in head kidney, kidney and spleen, abundant in intestine and gill, less abundant in liver, brain, heart and gonad, least in muscle and skin. The level of Nramp mRNA in embryos gradually increases during embryogenesis from blastula stage to fry stage. Challenge of turbot with pathogenic bacteria, Vibrio anguillarum, elevated Nramp mRNA levels in liver and spleen. The Nramp transcripts were detected in turbot embryonic cell line (TEC). Challenge of the TEC cell cultures with pathogenic bacteria, V. anguillarum, significantly elevated Nramp mRNA levels in TEC cell cultures.