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Objective:To investigate the effects of endoplasmic reticulum(ER)stress on the stability of atherosclerotic plaques in mice by examining the action of lipopolysaccharide(LPS)-induced Toll-like receptor 4(TLR4)on the protein expression levels in the ER stress pathway in atherosclerotic plaques of polipoprotein E gene knockout (ApoE -/-) mice. Methods:From October 2015 to February 2016, 24 ApoE -/-mice were randomly divided into the control group, the LPS group and the TAK group after 10 weeks of high-fat feeding(n=8, each group). After 10 weeks of intervention, peripheral blood was extracted by removing the eyeballs for the measurement of total cholesterol(TC), triglycerides(TG)and oxidized low density lipoprotein(ox-LDL). Then mice were sacrificed to obtain carotid and aortic specimens.Immunohistochemistry was used to detect the expression of carotid plaque macrophages(MOMA-2), smooth muscle actin(α-actin), TLR4, interleukin-1β(IL-1β), interleukin-6(IL-6), tumor necrosis factor-α(TNFα)and nuclear factor-κ-gene binding(NFκB). Western blotting was used to determine the expression of PKR-like eukaryotic initiation factor 2αkinase(PERK), C/EBP-homologous protein(CHOP)and glucose-regulated protein 78(GRP78). Results:The levels of TC, TG and ox-LDL were elevated in the LPS group, compared with the control and TAK groups[(25.0±2.3) mmol/L vs. (20.2±1.6) mmol/L and (20.8±2.6) mmol/L, (1.3±0.1) mmol/L vs.(1.3±0.1) mmol/L and (1.0±0.1) mmol/L, (17.4±1.3) mmol/L vs.(15.8±1.6) mmol/L and (12.1±1.1) mmol/L, P<0.05]. The comparison of plaque morphology and pathology showed that the LPS group had a wider range of atherosclerotic plaques, more macrophages and fewer vascular smooth muscle cells than the control and TAK groups( P<0.05). The expression of TLR4, IL-1β, IL-6, TNFα, NFκB, PERK, CHOP and GRP78 was higher in the LPS group than in the control and TAK groups( P<0.05). Compared with the control group, the expression of PERK, CHOP and GRP78 was lower in the TAK group( P<0.05). The expression of TLR4, PERK, CHOP and GRP78 was higher in the LPS group. Conclusions:LPS-induced TLR4 can up-regulate the expression of proteins in the ER stress pathway, increase the secretion of inflammatory cytokines downstream of the ER stress pathway, aggravate lipid metabolism disorders and increase the instability of atherosclerotic plaques.
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Objective:To investigate the effects of endoplasmic reticulum(ER)stress on the stability of atherosclerotic plaques in mice by examining the action of lipopolysaccharide(LPS)-induced Toll-like receptor 4(TLR4)on the protein expression levels in the ER stress pathway in atherosclerotic plaques of polipoprotein E gene knockout (ApoE -/-) mice. Methods:From October 2015 to February 2016, 24 ApoE -/-mice were randomly divided into the control group, the LPS group and the TAK group after 10 weeks of high-fat feeding(n=8, each group). After 10 weeks of intervention, peripheral blood was extracted by removing the eyeballs for the measurement of total cholesterol(TC), triglycerides(TG)and oxidized low density lipoprotein(ox-LDL). Then mice were sacrificed to obtain carotid and aortic specimens.Immunohistochemistry was used to detect the expression of carotid plaque macrophages(MOMA-2), smooth muscle actin(α-actin), TLR4, interleukin-1β(IL-1β), interleukin-6(IL-6), tumor necrosis factor-α(TNFα)and nuclear factor-κ-gene binding(NFκB). Western blotting was used to determine the expression of PKR-like eukaryotic initiation factor 2αkinase(PERK), C/EBP-homologous protein(CHOP)and glucose-regulated protein 78(GRP78). Results:The levels of TC, TG and ox-LDL were elevated in the LPS group, compared with the control and TAK groups[(25.0±2.3) mmol/L vs. (20.2±1.6) mmol/L and (20.8±2.6) mmol/L, (1.3±0.1) mmol/L vs.(1.3±0.1) mmol/L and (1.0±0.1) mmol/L, (17.4±1.3) mmol/L vs.(15.8±1.6) mmol/L and (12.1±1.1) mmol/L, P<0.05]. The comparison of plaque morphology and pathology showed that the LPS group had a wider range of atherosclerotic plaques, more macrophages and fewer vascular smooth muscle cells than the control and TAK groups( P<0.05). The expression of TLR4, IL-1β, IL-6, TNFα, NFκB, PERK, CHOP and GRP78 was higher in the LPS group than in the control and TAK groups( P<0.05). Compared with the control group, the expression of PERK, CHOP and GRP78 was lower in the TAK group( P<0.05). The expression of TLR4, PERK, CHOP and GRP78 was higher in the LPS group. Conclusions:LPS-induced TLR4 can up-regulate the expression of proteins in the ER stress pathway, increase the secretion of inflammatory cytokines downstream of the ER stress pathway, aggravate lipid metabolism disorders and increase the instability of atherosclerotic plaques.
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Objective To explore the relationship between ambient temperature variation and blood pressure fluctuations in acute ischemic stroke patients.Methods Clinical data of 5 730 ischemic stroke patients hospitalized at the Departments of Neurology and Geriatrics of The Second Hospital of Tianjin Medical University and air temperature data during the corresponding period were retrospectively analyzed.The relationship between air temperature and blood pressure in patients with acute ischemic stroke was analyzed.Results Of 5 730 patients,4 428 (77.28％)had hypertension and most of them were male(56.26％ 3 362 cases).The systolic and diastolic blood pressure levels were higher in hypertensive males than in hypertensive females[(153.9 ± 21.7) mmHg vs.(150.7 ± 23.6)mmHg,(85.9±13.3)mmHg vs.(83.0±12.5)mmHg,1 mm Hg=0.133 kPa,both P＜0.05].The systolic pressure tended to increase and diastolic pressure tended to decrease with increasing age (both P ＜ 0.05).The systolic and diastolic blood pressure levels of patients were slightly higher in autumn and winter than in spring and summer (P ＜ 0.05).The mean monthly maximum and minimum temperature had negative correlations with the systolic blood pressure of patients.There was a linear positive correlation between the average monthly diurnal temperature range and the systolic and diastolic blood pressure.The systolic or diastolic blood pressure increased by 0.088 mmHg or 0.076 mmHg respectively with each 1 ℃ drop in the mean monthly maximum and minimum temperature.The systolic or diastolic blood pressure increased by 1.043 mmHg or 0.654 mmHg respectively with each 1 ℃ increase in the average monthly diurnal temperature range.Conclusions Hypertension is a risk factor for ischemic stroke,and ambient temperature variation is related to baseline blood pressure fluctuations in hypertensive patients with acute ischemic stroke.The temperature reduction and the increase of average diurnal temperature rang can lead to the elevation of blood pressure,which is more obvious in autumn and winter,especially in elderly patients.
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Objective To investigate the effect of different serum sodium levels on heart function and prognosis in very elderly patients with heart failure. Methods Totally 152 elderly patients(aged ≥ 85 years)with hyponatremia were enrolled.Based on the serum sodium level ,they were divided into mild(125 mmol/L ≤ Na+ < 135 mmol/L) ,moderate(125 mmol/L ≤ Na+ < 135 mmol/L) ,and severe hyponatremia(Na+ < 115 mmol/L)groups ,and 76 patients with normal blood sodium level(Na+ ≥ 135 mmol/L)were selected as control group. The general data ,levels of serum creatinine and N-terminal pro-brain natriuretic peptide (NTproBNP)and prognosis were compared among the above groups. Results Compared with the control group ,patients with severe hyponatremia were much older ,with more diuretics administration ,higher level of serum creatinine , lowerlevelofeGFRandleftventricularejectionfractions[(38.1±3.9)％ vs.(45.2±9.7)％ ].There were higher incidences of coronary atherosclerotic heart disease [72.4％ (n=21)vs. 56.6％ (n=43)] ,diabetes[41.4％ (n=12)vs. 23.7％ (n=18)] ,chronic renal insufficiency [22.6％ (n=8)vs. 11.8％ (n=9)] ,stroke[20.6％ (n=6)vs. 9.2％ (n=7)]in patients with severe hyponatremia compared with other groups. The severe hyponatremia group showed significantly higher levels of NTproBNP [(4823. 9 ± 588. 1 )ng/L v s. (1124. 4 ± 349. 1 )ng/L ,(1836. 2 ± 369. 3 )ng/L ,(2894. 1 ± 687. 3 )ng/L ]and higher rates of mortality [27.6％ (n=8) vs.5.3％ (n=4) ,7.6％ (n=6) ,13.6％ (n=6)]as compared to the control group ,mild and moderate hyponatremia groups. Furthermore ,length of stay in hospital were markedly longer in patients with severe hyponatremia than those with mild and moderate hyponatremia[(11.1 ± 7.1)d vs. (19.6 ± 5.7)d ,(16.1 ± 4.2)d] . Conclusions Hyponatremia is a common type of electrolyte disorder in very elderly patients with heart failure ,and severe hyponatremia may predictand increased risk of death.
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Objective To survey a prevalence of osteoporosis and prevalence of osteoporosis combined with hyponatremia in elderly hospitalized patients,and their risk factors.Methods We enrolled 2496 elderly hospitalized patients with detected plasma levels of sodium,calcium,25 (OH) D3,PTH,plasma PINP,and β-CTX.At the same time,sex,age,height,weight,smoking history,drinking history and BMI(kg/m2) in form of a questionnaire were recorded and calculated.The risk factors for osteoporosis were analyzed using multivariate Logistic regression method.Results The osteoporosis prevalence was 12.2％ (305/2496 inpatients)with 31.5 ％ (96/305)in male,68.5％ (209/305)in female(x2 =4.651,P=0.031).The prevalence of osteoporosis with hyponatremia was 27.5 ％ (84/305),with 24.8 ％ (21/84) in male and 75.2 ％ (63/84) in female(x2 =9.251,P=0.025).As compared with three groups of non-osteoporosis,normal serum Na+ with and without osteoporosis,the osteoporosis patients with hyponatremia were more aged,in a higher proportion of women and smokers,in lower BMI,and in low levels of serum sodium,BMD 25(OH)D3 (F=13.783,0.861,7.146,24.520,0.548,x2 =15.113、4.472;P =0.001,0.000,0.021,0.015,0.003,0.021,0.005).Multivariate Logistic regression analysis showed that aging,female,low BMI,smoking history,drinking history,low plasma 25(OH)D3 level,low plasma PINP level,and high plasma β-CTX level were the risk factors for osteoporosis(OR 4.215,2.271,3.176,2.013,1.237,3.987,1.843,1.972;all P＜0.05).Conclusions The osteoporosis prevalence is high in elderly patients,especially in old women.The risk factors for osteoporosis are diverse,and clinical conditions of osteoporosis patients with hyponatremia are much more severe than the others.More efforts should be given to them and need to be focused on the complications of osteoporosis.
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Objective To explore the correlation of serum homocysteine(Hcy)levels and hypertrophy of left ventricle in very elderly hypertensive patients.Methods According to plasma Hcy levels,patients with essential hypertension (n=378) were divided into non H-type hypertension group (n=142) and H-type hypertension group (n=236). Height, weight, reg?ular medication, blood pressure, renal function, blood lipid profile and the concentration of plasma Hcy were recorded. Color Doppler ultrasonic equipment was used to determine the morphology and structure of left ventricle. The correlation between plasma Hcy and left ventricle remodeling was analyzed. Results The ratio of left ventricular hypertrophy was higher in H-type hypertension group than that in non H-type hypertension group(45.8%vs 24.6%,χ2=16.81,P<0.001). Patients in H-type hypertension group had higher systolic blood pressure, higher plasma level of Hcy and larger left ventricular posterior wall thickness(LVPWT), larger interventricular septal thickness (IVST) and increased left ventricular mass index (LVMI) compared to those in non H-type hypertension group(162.20 ± 14.97)vs(149.70 ± 5.06)mmHg,(19.76 ± 5.83)μmol/L vs (9.53±0.72)μmol/L,(9.77±2.35)vs(9.21±2.68)mm,(9.74±3.15)vs(8.51±2.42)mm,(118.64±39.38)vs(101.85±41.71)g/m2 respectively, all P<0.05). There was a positive correlation between LVMI and Hcy(r=0.381,P<0.001). Multivariable Lo?gistic regression analysis showed that hyperhomocysteinemia was an independent risk factor of LVMI. Conclusion High plasma Hcy level is an independent risk factor of LVMI, which works together with hypertension to promote left ventricular re?molding.