Aged ; Drug-Related Side Effects and Adverse Reactions ; blood ; therapy ; Emergency Treatment ; Female ; Hemoperfusion ; Humans ; Hypnotics and Sedatives ; poisoning ; Male ; Middle Aged ; Serum ; chemistry

BACKGROUND:Endoplasmic reticulum stress participates in the occurrence and development of many diseases, such as atherosclerosis, diabetes, and Alzheimer’s disease. GRP78 is a marker of endoplasmic reticulum stress. The expression of GRP78 reflects the degree of endoplasmic reticulum stress.
OBJECTIVE:To investigate the effect of cyclic stretch on GRP78 expression of L6 rat myoblasts, and to identify the relationship between cyclic stretch and endoplasmic reticulum stress.
METHODS:In vitro culture-tensile stimulation models of myoblasts of L6 rats were established successful y. The expression of GRP78 of myoblasts exposed to cyclic stretch was determined by reverse transcription-PCR and western blot assay. Stretch groups were subjected to 15%surface elongation at a frequency of 10 cycles per minute, over a period of 1, 6, 12 and 24 hours. cells were simultaneously seeded on a plate in the control and experimental groups with no stimulation.
RESULTS AND CONCLUSION:The expression of GRP78 mRNA was continuously elevated over time after stretched treatment, and significant differences were detected as compared with the control group (P<0.05). GRP78 protein expression began to increase at 1 hour after stretched treatment, was significantly increased at 6 hours, peaked at 24 hours, and significant differences were visible as compared with the control group (P<0.05). In conclusion, cyclic stretch induced the occurrence of endoplasmic reticulum stress, which was enhanced with prolonged time. However, prolonged stretch caused severe endoplasmic reticulum stress and leaded to apoptosis of myoblasts.

OBJECTIVEThis study investigated the role and mechanism of calcineurin (CaN)-nuclear factor of activated T cells (NFAT) pathway in the myoblast apoptosis induced by cyclic tensile strain.

METHODSMyoblasts were cultured using an in vitro-mechanical stimulation model and imposed with tension for different hours with a multi-channel cell stress loading system. Cyclosporine (CsA) was used as CaN inhibitor to clarify the role of CaN in the apoptosis induced by cyclic stress. Hochest 33258 staining and flow cytometry detection were performed to detect the apoptotic cells. Real-time polymerase chain reaction was conducted to detect the mRNA expression of CaN and NFAT. Protein levels of NFAT3 were evaluated by Western blot.

RESULTSThe apoptosis rate increased with the extension of loading time. The mRNA expression of the CaN subunits, CnA and CnB, and the protein levels of NFAT3 also increased. When the myoblasts were incubated with CsA, the apoptosis rate decreased, the mRNA expression of CnA and NFAT3 significantly decreased, and the NFAT3 protein expression levels became significantly lower than those of the groups without CsA.

CONCLUSIONContinuous cyclic tensile stress can induce myoblast apoptosis. The CaN-NFAT signaling pathway may be involved in the cyclic stretch-induced apoptosis of myoblasts.

Apoptosis ; Calcineurin ; genetics ; Cyclosporine ; Flow Cytometry ; Myoblasts ; physiology ; NFATC Transcription Factors ; metabolism ; Real-Time Polymerase Chain Reaction ; Signal Transduction ; T-Lymphocytes

OBJECTIVETo evaluate wave intensity (WI) on left ventricular (LV) performance in the different hypertensive remolding hearts.

METHODS105 hypertensive and 98 control subjects were underwent noninvasive evaluation of carotid arterial wave intensity, LV structure and function.

RESULTS(1) There were increasing trends in the levels of blood pressure, LV end-diastolic diameter and LV mass index in the control, normal geometry group, concentric remodeling group, concentric and eccentric hypertrophy group. LV ejection fraction increased in the concentric hypertrophy group and decreased in the eccentric hypertrophy group in which mid-wall fractional shortening showed a decreasing trend. LV diastolic filling pressure presented increased progression accompanied by LV remodeling (P < 0.05). (2) Transient acceleration wave intensity (W1) in hypertensive subjects were higher than that in the control (P < 0.05). Transient deceleration wave intensity (W2) was lower than that in the control (P < 0.05). (3) W1 in the concentric hypertrophy group was higher and lower in the eccentric hypertrophy, compared with that in the control group, normal geometry group and concentric remodeling group (P < 0.05). W2 was lower in concentric hypertrophy group and eccentric hypertrophy group than that in the control, normal geometry group and concentric remodeling group (P < 0.05).

CONCLUSIONWI is a noninvasively obtained, clinically useful parameter for evaluation of LV performance.

Aged ; Blood Flow Velocity ; physiology ; Carotid Artery, Common ; physiopathology ; Case-Control Studies ; Female ; Humans ; Hypertension ; physiopathology ; Male ; Middle Aged ; Pulsatile Flow ; physiology ; Ventricular Function, Left ; physiology ; Ventricular Remodeling

OBJECTIVETo evaluate transient deceleration wave intensity (W2) of carotid artery on left ventricular diastolic function.

METHODS40 patients with hypertension and 43 healthy volunteers were enrolled and W2 of carotid artery of the both sides were measured. The parameters of left ventricular diastolic function by traditional and tissue Doppler imaging and NT-proBNP (N-terminal probrain natriuretic peptide) were measured.

RESULTS(1) W2 is not different between two sides of carotid artery. W2 in hypertension was lower than the control, especially in left side(1126 +/- 996 mmHg x m/s3 vs 1690 +/- 1126 mmHg x m/s3, P < 0.01). (2) The correlation of W2 and else parameters were analyzed. There were notably decreasing in left ventricular diastolic function of the hypertensive group than the control, for example, the ratio of peak velocity of early filling of mitral flow to peak early diastolic motion velocity of mitral annulus (E/Em, 9.37 +/- 3.32 vs 7.39 +/- 1.83, P < 0.01) and NT-proBNP (94.6 +/- 48.5 vs 45.2 +/- 13.8, P < 0.01). (3) The correlation analysis showed negative relation between W2 and E/Em (r = - 0.46, P < 0.05) and negative relation between W2 and NT-proBNP (r = -0.21, P < 0.05).

CONCLUSIONNew carotid W2 by non-invasive technology for hemodynamics is a deserving parameter in early evaluating left ventricular diastolic function.

Adult ; Carotid Artery, Common ; physiopathology ; Female ; Humans ; Hypertension ; physiopathology ; Male ; Middle Aged ; Natriuretic Peptide, Brain ; blood ; Peptide Fragments ; blood ; Ventricular Dysfunction, Left ; diagnosis ; physiopathology ; Ventricular Function, Left

OBJECTIVETo explore the effectiveness related indicators which might help identify the indications of Tongxinluo Capsule () and Kangxin Capsule () targeting on qi deficiency and blood stasis pattern in Chinese medicine (CM) in the treatment of angina pectoris.

METHODSThe data from a multicenter, randomized and double-blinded study conducted at 5 centers in China were obtained for the analysis. A total of 239 patients with angina pectoris and CM syndrome of qi deficiency and blood stasis were randomly assigned in a 1:1 ratio to Tongxinluo Capsule group (119 cases) and Kangxin Capsule group (120 cases). Angina effectiveness and electrocardiogram (ECG) improvement were selected as the therapeutic outcomes.

RESULTSAfter a 4-week treatment, the effective rates of Tongxinluo Capsule and Kangxin Capsule were 43.70% and 25.00%, respectively (P <0.05). Serum low-density lipoprotein (LDL) level was found to influence the effectiveness of Tongxinluo Capsule which had higher effective rate in the patients with lower level of LDL. Heart rate was found to influence the effectiveness in the patients treated with Kangxin Capsule which had higher effective rate in the patients with heart rate [Symbol: see text]80 beats/min.

CONCLUSIONLDL level and heart rate were the indicators which help indentify the indications of Tongxinluo Capsule and Kangxin Capsule, respectively, in the treatment of angina pectoris with CM syndrome of qi deficiency and blood stasis.

Adult ; Aged ; Angina Pectoris ; blood ; drug therapy ; physiopathology ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Female ; Heart Rate ; drug effects ; physiology ; Humans ; Lipoproteins, LDL ; blood ; Male ; Middle Aged ; Patient Dropouts ; Platelet Count ; Treatment Outcome

Objective To discuss the expression and clinical significance of microRNA(miR)- 766 in chil-dren with polyarticular juvenile idiopathic arthritis (poly - JIA). Methods A total of 23 children with poly - JIA who received treatment at the Department of Rheumatology,the Affiliated Children′s Hospital of Capital Institute of Pediat-rics,from November 2014 to September 2016,were enrolled as research group,and 24 healthy children at the same age were selected as healthy control group,while 24 children with oligoarticular juvenile idiopathic arthritis (oligo - JIA) and 19 children with juvenile ankylosing spondylitis (JAS)were selected as case - control groups. The expression lev-els of miR - 766 in plasmas were detected by real - time quantitative polymerase chain reaction (qPCR). The clinical diagnostic values were analyzed by operating characteristic curve (ROC). Correlations between the expression levels of miR - 766 and clinical,laboratory results were analyzed by conducting Pearson correlation coefficient analysis. Results Compared with the healthy control group and case - control group,the expression levels of miR - 766 in poly - JIA group decreased,and the differences were statistically significant (t = 6. 897,6. 446,6. 218,all P < 0. 001). There was no statistical difference of miR - 766 levels in plasma between case - control groups and healthy control group (P >0. 05). Compared with the healthy control group,the area under ROC curve of miR - 766 was 0. 938 (95％ CI:0. 872 -1. 000),and when the cutoff value of miR - 766 was 6. 083 pmol/ L,the sensitivity was 87. 0％ and the specificity was 91. 7％ . Compared with oligo - JIA and JAS,the area under ROC curves of miR - 766 was 0. 908 (95％ CI:0. 819 -0. 996)and 0. 927 (95％ CI:0. 865 - 1. 000),respectively. Correlation analysis indicated that the level of miR - 766 in plasma of poly - JIA children was positively associated with hemoglobin (r = 0. 651,P < 0. 001),but negatively asso-ciated with the 28 - joint Disease Activity Score (DAS28)and the percentage of type 1 helper T cells(Th1％)(r =- 0. 434,P = 0. 038;r = - 0. 417,P = 0. 008). Conclusions The expression levels of plasma miR - 766 in poly - JIA are significantly decreasing. miR -766 may serve as an evaluation indicator for the diagnosis and prognosis of poly - JIA.

Objective To investigate the effect of progressive early bed physical activity on blood flow in lower limb of patients on mechanical ventilation in intensive care unit (ICU). Methods Adult patients with mechanical ventilation ≥ 72 hours admitted to ICU of the Affiliated Hospital of Zunyi Medical University from February 22nd to November 30th, 2016 were enrolled. The patients were randomly divided into experimental group and control group by random number table method. Patients in the two groups were given the same basic treatment, including antibiotics, analgesia and sedation, mechanical ventilation, nutritional support, and routine ICU activities such as maintaining functional position of limbs and raising of bed head. On the basis of those, the experimental group was given early bed physical activity with gradual enhancement of grades Ⅰ-Ⅲ according to the nerve, circulation and respiration situations, such as passive/active exercise of the bicycle, straight leg lifting exercise, etc. The exercise intensity was evaluated with target heart rate, and the exercise was performed for 15-30 minutes at a time, twice a day. The control group was given intermittent pneumatic compression (IPC), 30 minutes in each time, twice a day. Mean blood flow and blood volume were measured before and immediately, 5, 10 and 15 minutes after intervention on the 3rd day. Heart rate and blood pressure were measured at 5 minutes before intervention, during 5 minutes, and 5, 10, 15, 30 minutes after intervention on the 3rd day. Results 214 adult patients were selected, after excluding the patients who died during the intervention or gave up treatment, 160 patients were included in the data analysis, with 81 in the experimental group and 79 in the control group. The mean blood flow velocity and blood volume were increased in both groups, and the mean blood flow velocity and blood flow volume in the experimental group were significantly increased and lasted longer than those in the control group [mean blood flow velocity (mm/s) of the experimental group were 11.92±1.06, 18.19±0.17, 17.24±0.14, 15.48±0.12, 12.68±0.16, and that of the control group were 12.01±1.41, 15.65±0.18, 12.91±0.14, 12.13±0.12, 11.59±0.16, respectively, the time effect was F = 1 043.101, P = 0.000, the intervention effect was F = 151.001, P = 0.000, and the interaction effect between intervention and time was F = 224.830, P = 0.001; the blood volume (mL/min) of the experimental group were 3.39±0.96, 5.59±0.11, 5.16±0.12, 4.19±0.10. 3.35±0.09, and that of the control group were 3.28±0.82, 4.04±0.11, 3.40±0.12, 3.02±0.10, 3.00±0.10, respectively, the time effect was F = 680.405, P = 0.000, the intervention effect was F = 125.359, P = 0.000, and the interaction effect between intervention and time was F = 79.631, P = 0.012]. The heart rate and blood pressure of the two groups of patients in the course of intervention were increased first, then decreased and then slowly recovered to the change trend before intervention, but the index of the experimental group fluctuated greatly [heart rate (bpm) of the experimental group were 97.64±1.50, 113.91±1.36, 105.96±1.34, 98.52±1.48, 97.84±1.46, 97.54±1.48, and that of the control group were 97.03±1.57, 105.39±1.38, 96.76±1.35, 96.54±1.50, 97.22±1.48, 96.53±1.49, respectively, the time effect was F = 235.030, P = 0.000, the intervention effect was F = 39.473, P = 0.000, and the interaction effect between intervention and time was F = 3.494, P = 0.063; the systolic blood pressure (mmHg, 1 mmHg = 0.133 kPa) of the experimental group were 118.57±1.06, 133.05±1.01, 120.44±1.10, 117.78±1.07, 117.65±1.01, 118.14±1.00, and that of the control group were 118.10±1.08, 126.68±1.02, 118.23±1.11, 117.48±1.08, 118.04±1.03, 118.90±1.10, respectively, the time effect was F = 336.604, P = 0.000, the intervention effect was F = 26.350, P = 0.000, and the interaction effect between intervention and time was F = 0.948, P = 0.332; the diastolic blood pressure (mmHg) of the experimental group were 68.07±0.72, 72.79±0.73, 70.68±0.74, 69.30±0.72, 68.73±0.74, 67.80±0.73, and that of the control group were 68.51±0.73, 72.03±0.74, 70.05±0.75, 69.10±0.73, 68.41±0.75, 67.85±0.74, respectively, the time effect was F = 286.390, P = 0.000, the intervention effect was F = 4.812, P = 0.000, and the interactive effect between intervention and time was F = 0.055, P = 0.815]. Conclusions The effects of progressive early bed physical activity on the mean blood flow velocity and blood volume of lower limbs in ICU patients with mechanical ventilation are better than those of IPC. Although the fluctuation of heart rate and blood pressure is large, it does not cause any harm to the patients.

Objective To construct RNAi combinant adenoviral expressive vectors specific to p65 subunit of NF-?B and to observe their gene silencing effect on p65 subunit.Methods Three pairs of complementary. single-strand DNA oligos targeting three various sites of p65 mRNA were designed and synthesized.Annealling was used to generate double-strand oligos(ds-oligos),and then the ds-oligos were cloned into pENTR~TM/u6 to generate the entry clone named pENTR.Recombination reaction in vitro with the pENTR and pAd/BLOCK-iT~TM- DEST was used to creat the adenovirus plasmid which contains the RNAi cassette.Then,the adenovirus plasmids digested with PacI were transfected into HEK293A cells to product adenovirus,and latter infected the HEK293A cells to amplify the adenoviral stock.Plaque forming assay was used to titer the adenoviral stock.The p65 gene silencing effect induced by the RNAi adenovirus was detected by Western blot and immunocytochemistry assay in ECV304 cells.Results The RNAi adenovirus specific to p65 subunit of NF-?B were produced with titer of 3.0 x 10~9pfu/ml to 2.5?10~10pfu/ml.The expression of p65 protein in ECV304 cells could be down-regulated efficiently by the RNAi adenovirus 48-72 h after infection,which would last for more than 6 days after infection.Conclusion RNAi adenovirus is an important tool inhibiting the expression of target gene efficiently.

Objective:To investigate the proportion of helper T lymphocytes 22(Th22) and levels of interleukin(IL)-22 in peripheral blood of children with juvenile idiopathic arthritis (JIA), and analyze their relevance with JIA-related inflammatory cytokines.Methods:A total of 30 children with JIA who received treatment at the Department of Rheumatology, the Affiliated Children′s of Capital Institute of Pediatrics from November 2018 to December 2019 were enrolled as JIA group, and 12 healthy children at the same age were selected as healthy control group.The percen-tage of Th22 cells in peripheral blood was detected using flow cytometry.Concentrations of IL-22, IL-6, tumor necrosis factor(TNF-α), IL-17 and IL-10 were measured by enzyme-linked immunosorbent assay.Statistical analysis of the relevance of Th22 cells, IL-22 levels and inflammatory cytokines levels of IL-6, TNF-α, IL-17 and IL-10 in JIA were performed by Pearson test. Results:The proportion of Th22 cells in peripheral blood of patients in JIA group[(0.94±0.26)%] was higher than that of the healthy control group [(0.46±0.29)%], and the difference was statistically significant ( t=2.227, P<0.05). Plasma level of IL-22 of patients in JIA group[(185.2±11.93) ng/L] was significantly higher than that of healthy control group[(114.7±6.29) ng/L], and the difference was statistically significant ( t=3.632, P<0.001). The proportion of Th22 cells and the levels of plasma IL-22 in JIA patients were positively correlated with plasma levels of IL-6 (Th22: r=0.501, IL-22: r=0.573, all P<0.01), IL-17 (Th22: r=0.686, P<0.001; IL-22: r=0.445, P<0.01) and IL-10 (Th22: r=0.609, IL-22: r=0.284, all P<0.001). There was no relationship for Th22 cells and plasma levels of IL-22 with TNF-α. Conclusions:The proportion of Th22 cells and plasma levels of IL-22 significantly increase in peripheral blood of JIA patients and correlated with JIA-related inflammatory cytokines, which may play a potential role in the pathogenesis of JIA disease.