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Objective:To investigate the effect of acupoint stimulation assisted anesthesia on the agitation during recovery and the levels of serum opioids (Opiorphin) and amyloid A (SAA) in elderly patients after hip fracture surgery.Methods:Eighty-six older patients who underwent hip fracture surgery in Shaoxing Second Hospital from February 2020 to September 2021 were randomly divided into the routine group and the research group, each with 43 patients. They were given acupoint sham stimulation and acupoint stimulation respectively, and the general indexes of the two groups, recovery quality, cognitive function and changes in serum Opiorphin and SAA levels were compared.Results:There were no differences in operation time, anesthesia time, recovery time and intraoperative blood transfusion between the two groups ( P>0.05). The dosage of remifentanil in the research group was significantly lower than that in the routine group: (270.64 ± 17.62) μg vs. (291.82 ± 23.34) μg, P<0.05. The incidence of agitation during the recovery period in the research group was significantly lower than that in the routine group: 13.95% (6/43) vs. 48.84% (21/43), P<0.05. The mini-mental state examination (MMSE) scores in the research group at 12, 24 and 48 h after operation were significantly higher than those in the routine group: (22.80 ± 2.04) scores vs. (19.31 ± 3.61) scores, (24.92 ± 2.44) scores vs. (21.49 ± 3.58) scores, (26.73 ± 2.57) scores vs. (24.23 ± 3.95) scores, there were statistical differences ( P<0.05). The serum Opiorphin level at 24 h after operation in the research group was higher than that in the routine group: (32.74 ± 8.57) mg/L vs. (25.40 ± 6.36) mg/L; and the SAA level was lower than that in the routine group: (157.36 ± 10.24) mg/L vs. (204.37 ± 15.56) mg/L, there were statistical differences ( P<0.05). Conclusions:Acupoint stimulation adjuvant anesthesia can reduce the occurrence of agitation during the recovery period of elderly patients with hip fracture, reduce the dosage of anesthetics, reduce postoperative cognitive impairment, regulate serum Opiorphin and SAA levels, and help early postoperative recovery.
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Herein, we define the role of ferroptosis in the pathogenesis of diabetic cardiomyopathy (DCM) by examining the expression of key regulators of ferroptosis in mice with DCM and a new ex vivo DCM model. Advanced glycation end-products (AGEs), an important pathogenic factor of DCM, were found to induce ferroptosis in engineered cardiac tissues (ECTs), as reflected through increased levels of Ptgs2 and lipid peroxides and decreased ferritin and SLC7A11 levels. Typical morphological changes of ferroptosis in cardiomyocytes were observed using transmission electron microscopy. Inhibition of ferroptosis with ferrostatin-1 and deferoxamine prevented AGE-induced ECT remodeling and dysfunction. Ferroptosis was also evidenced in the heart of type 2 diabetic mice with DCM. Inhibition of ferroptosis by liproxstatin-1 prevented the development of diastolic dysfunction at 3 months after the onset of diabetes. Nuclear factor erythroid 2-related factor 2 (NRF2) activated by sulforaphane inhibited cardiac cell ferroptosis in both AGE-treated ECTs and hearts of DCM mice by upregulating ferritin and SLC7A11 levels. The protective effect of sulforaphane on ferroptosis was AMP-activated protein kinase (AMPK)-dependent. These findings suggest that ferroptosis plays an essential role in the pathogenesis of DCM; sulforaphane prevents ferroptosis and associated pathogenesis via AMPK-mediated NRF2 activation. This suggests a feasible therapeutic approach with sulforaphane to clinically prevent ferroptosis and DCM.
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Objective:To evaluate the effects of different electrolyte solutions on blood washing in cardiac surgery with cardiopulmonary bypass (CPB).Methods:Sixty patients, aged 18-80 yr, weighing 50-100 kg, undergoing cardiac surgery with CPB with expected banked blood transfusion 4-6 U in our hospital, were divided into 3 groups ( n=20 each) by a random number table method: compound electrolyte injection group (group A), sodium bicarbonate Ringer′s solution group (group B) and normal saline group (group C). Banked blood and salvaged autologous blood were washed with compound electrolyte injection, sodium bicarbonate Ringer′s solution and normal saline.Banked and autologous blood was collected before washing and immediately after washing for blood gas analysis.The osmotic fragility of red blood cells was measured by colorimetry, and the concentration of 2, 3-diphosphoglycerate (2, 3-DPG) was determined by enzyme-linked immunosorbent assay. Results:Compared with the baseline before washing, the concentrations of K +, Glu and Lac in banked blood were significantly decreased, the concentrations of K + in banked blood were increased, and the concentrations of Glu and Lac in autologous blood were decreased, the osmotic fragility of erythrocytes was increased, and the concentrations of 2, 3-DPG in banked and autologous blood were increased after washing in the three groups ( P<0.05). Compared with group C, the concentrations of Na + and Cl - in banked and autologous blood were significantly decreased, the concentrations of K + in banked and autologous blood were increased, the osmotic fragility of erythrocytes in banked and autologous blood was decreased, and the concentrations of 2, 3-DPG in banked and autologous blood were increased in A and B groups ( P<0.05). Compared with A and C groups, BE in banked and autologous blood were significantly increased after washing in group B than in A and C groups ( P<0.05). After washing, Ca 2+ was detected in banked and autologous blood in group B, however, Ca 2+ was not detected in banked and autologous blood in group A and group C. Conclusions:Compound electrolyte solution and sodium bicarbonate Ringer′s solution provide better efficacy when used for blood washing in cardiac surgery with CPB, and sodium bicarbonate Ringer′s solution can also improve the acidic and calcium-free internal environment of blood.
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In eukaryotes, the basic structural unit of chromatin is the nucleosome, and genomic DNA iscompressed in chromatin. The presence of nucleosomes usually inhibits the biological processes that occuron the DNA templates, such as transcription, replication, repair, and recombination,. The histonevariant H2A.Z can regulate the structure of chromatin and affect the transcription process of genes, but itsdetailed regulation mechanism remains unclear. In this paper, the method of Förster resonance energytransfer (FRET) was used to detect the influence of sodium chloride, potassium chloride, manganesechloride, calcium chloride and magnesium chloride on the dissociation of nucleosomes. Then, the stabilitydifferences between the nucleosomes containing the histone variant H2A. Z and the conventionalnucleosomes were compared under the action of salt ions. Widom 601 DNA sequence was labeled withdual fluorescence Cy3 and Cy5, and the dissociation of nucleosomes was reflected by the change offluorescence signal value. FRET results showed that the dissociation speed of nucleosomes containing thehistone variant H2A. Z under the action of sodium chloride, potassium chloride, manganese chloride, calcium chloride and magnesium chloride is slower than that of canonical nucleosomes, and the influenceof calcium chloride, manganese chloride and magnesium chloride on dissociation is more obvious thansodium chloride, potassium chloride. The results of electrophoresis analysis showed that the dissociationrate of nucleosomes containing histone variant H2A. Z was significantly lower than that of canonicalnucleosomes at 75℃. Fluorescence thermal shift (FTS) was used to further analyze the stability ofnucleosomes containing histone variant H2A.Z. It was found that the fluorescence signals of the two typesof nucleosomes showed two distinct growth periods, and the fluorescence signals generated in thedissociation process of the two types of nucleosomes showed two distinct growth periods. The temperaturecorresponding to the first increasing period of fluorescence signal in the dissociation process of H2A. Z-containing nucleosome is significantly higher than that in the dissociation process of the canonicalnucleosome, which indicated that the dissociation and denaturation temperature of the H2A.Z / H2B dimerin the nucleosome is higher than that of the canonical H2A / H2B dimer, and the H2A. Z-containingnucleosomes have high thermal stability. The results indicated that the structure of nucleosomes containingthe histone variant H2A.Z is more stable than that of canonical nucleosomes.
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Background Although transforming growth factor-β (TGF-β)/Smad signaling pathway is important in regulating the occurrence and development of pulmonary fibrosis, the pathogenesis of pulmonary fibrosis remains elusive. Objective To explore the functions of genes associated with TGF-β/Smad signaling pathway in the progression of pulmonary fibrosis. Methods A NIH-3T3 fibroblast model induced by TGF-β1 was established. The experiment samples were divided into a control group and a TGF-β1 treatment group. The control group was exposed to normal saline, while the TGF-β1 treatment group was exposed to 10 ng·mL−1 TGF-β1 for 12 h. The RNAs of the two groups were extracted, sequenced, and analyzed by bioinformatics methods to identify seven key genes in TGF-β pathway, including Dcn, Smad3, Smad7, Fbn1, Thbs1, TGF-β1, and TGF-β3. The gene expression levels of five markers [Collagen1α1, Collagen1α2, α-smooth muscle actin (α-SMA), TGF-β1, and TGF-β3] and the seven key genes were detected by quantitative real-time PCR (qRT-PCR). The proteins of the two groups were extracted. The important marker protein expression levels of Smad3, the phosphorylation of Smad3 (P-Smad3), and α-SMA were detected by Western blotting. At the same time, 30 healthy SPF-grade C57BL/6 mice were randomly divided into three groups, with 10 mice in each group: a control group, a SiO2 inhalation exposure group for 28 d (10 mice), and a SiO2 inhalation exposure group for 56 d (10 mice). The mice in the two treatment groups were exposed to a natural SiO2 environment for 4 h per day with a 10-min pause for breathing fresh air at 2 h intervals. The lung tissues of the mice were taken after execution. The changes of pulmonary fibrosis were detected by Masson staining, and mRNAs and proteins were extracted to detect the expression of the above key genes and proteins. Results The expression levels of the five marker genes Collagen1α1, Collagen1α2, α-SMA, TGF-β1, and TGF-β3 were significantly increased in the TGF-β1-induced NIH-3T3 fibroblasts than those in the control group (P < 0.01); the expression levels of P-Smad3 and α-SMA proteins increased significantly (P < 0.01); the expression results of the seven key genes screened in the TGF pathway were that Dcn and Smad3 were obviously down-regulated (P < 0.01), and Smad7, Fbn1, Thbs1, TGF-β1, and TGF-β3 were obviously up-regulated (P < 0.01). The changes in gene expression levels of the transcriptome sequencing showed the same trend. The results of Masson staining showed that the content of collagen fibers in the lung tissues also increased in the SiO2 inhalation exposure groups over time. In the mouse experiment, five marker genes were obviously up-regulated compared with the control group (P < 0.01); no obvious change was found in the expression of Smad3 protein, and the expression levels of P-Smad3 and α-SMA were obviously higher in the SiO2 exposure groups than those in the control group (P < 0.01); the expression levels of Dcn and Smad3 showed a down-regulated trend, while the expression levels of Smad7, Fbn1, Thbs1, TGF-β1, and TGF-β3 showed an up-regulated trend with the increase of SiO2 inhalation exposure days (P < 0.01). The expression levels of the above five marker genes, three important marker proteins, and seven key genes were consistent with the expression trends of TGF-β1-induced NIH-3T3 fibroblasts. Conclusion The expression levels of pulmonary fibrosis-related marker genes and proteins change significantly in TGF-β1-induced fibroblast cells, and the lung tissues of mice under natural SiO2 inhalation exposure has obvious fibrosis characteristics. Seven genes (Dcn, Smad3, Smad7, Fbn1, Thbs1, TGF-β1, and TGF-β3) may be involved in the regulation of pulmonary fibrosis by the TGF-β/Smad signaling pathway.
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Background The main pathological feature of silicosis is pulmonary fibrosis. Multiple miRNAs regulate the development of silicosis. Objective Using a fibroblast cell line, to explore the effect of miR-18a on the expression of extracellular matrix-related genes, and verify the mechanism. Methods The fibroblast cell line NIH-3T3 cells were transfected with miR-18a mimics or neurogenic locus notch homolog protein 2 (Notch2) small interfering RNA (siRNA). The mRNA expression changes of Acta2, Col1a1, and Notch2 were detected by real-time quantitative reverse transcription PCR (qRT-PCR), α-smooth muscle actin (α-SMA) and Notch2 were also detected at the protein level by Western blotting. To verify whether miR-18a could directly act on the complementary sequences of the Notch2 gene, human embryonic kidney HEK293T cells and the psiCHECKTM-2 vector were used. Results The results of qRT-PCR showed that in NIH-3T3 cells, the over-expression of miR-18a mimics for 36 h inhibited the mRNA expression of Col1a1 and Acta2 (P<0.05). The results of Western blotting showed that the protein expression abundance of α-SMA was decreased at 48 h of miR-18a mimics over-expression. The qRT-PCR results showed that the over-expression of miR-18a for 36 h had no significant effect on Notch2 gene expression, but the Western blotting results showed that the over-expression of miR-18a mimics inhibited the expression of Notch2 at the protein level. The results of the dual luciferase reporter vector assay showed that in HEK293T cells, both over-expressed miR-18a mimics and inhibitors for 24 h demonstrated that Notch2 is a direct target gene of miR-18a. When Notch2 was inhibited for 36 h, the qRT-PCR results showed that Acta2 and Col1a1 were down-regulated (P < 0.05), and the results of Western blotting showed that α-SMA protein was also inhibited. Conclusion The findings indicate that miR-18a could inhibit the expression of extracellular matrix-related genes of NIH-3T3 cells by directly acting on the 3’UTR of target gene Notch2.
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Objective To evaluate the transmural myocardial strain in three specific layers of the left ventricle at the papillary muscle level in short-axis view in SD rats before and after doxorubicin administration usmg myocardial layer-specific strain imaging based on two-dimensional ultrasound speckle tracking imaging (2D-STI),and to demonstrate the myocardial mechanical characteristics of doxorubicininduced early-stage acute cardiac toxicity in rats.Methods Thirty-two SD male rats weighing 300-350 g were randomly divided into a doxorubicin group (DOX group,n=16) and a control group (n=16).In the doxorubicin group,doxorubicin hydrochloride (concentration,2 mg/ml) was injected intraperitoneally at a single dose of 12 mg/kg,while the control group was given equal volume of 0.9% sodium chloride solution.LVEDD,LVESD,IVSd,LVPWd,FS,and LVEF were measured and derived using two-dimensional gray-scale echocardiography at the left ventricular papillary muscle level in short-axis view at three time points (before administration and 24 and 48 hours after administration).The circumferential strain in the subendocardium,medium,and subepicardium at the left ventricular papillary muscle level in short-axis view were obtained using ultrasonic 2D-STI.The values of FS,LVEF,and the global myocardial circumferential strain in different layers of the left ventricular wall at the papillary muscle level in short axis view at three time points were compared between the two groups.After echocardiographic examinations at 48 h and 72 h,the hearts of three rats in each group were randomly selected,sliced,and HE-stained for myocardial pathological observation.Results In both groups,there was a circumferential strain gradient of the left ventricular wall at the papillary muscle level in the short-axis view:subendocardium > medium > epicardial myocardium.In the DOX group,the circumferential strain in the subendocardial myocardium decreased at 48 hours after DOX administration;the difference was statistically significant between the two groups (-25.13± 10.6 vs -17.04± 2.89,t=2.3,P < 0.05).There was no significant difference in myocardial circumference strain in the three layers,as well as LVEDD,LVESD,IVS,LVPW,FS,or LVEF at three time points between the control group and DOX group (P > 0.05).The pathological changes were mainly myocardial cell edema,vascular degeneration,myocardial nucleus atrophy,dissolution,interstitial edema,and capillary dilatation in the doxorubicin group,which were especially obvious in subendocardial cardiomyocytes.Conclusion 2D-STI technology based layer-specific strain imaging could be used to detect and quantitatively evaluate the deformation damage of the transmural left ventricular wall in SD rats.
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A lot of researches suggest that brachial -ankle pulse wave velocity (baPWV ) is closely associated with large artery stiffness , which has been widely used to assess atherosclerotic severity .Some evidence indicates that baPWV is an independent predictor for occurrence and mortality of cardiovascular events .However , there are few domestic and foreign studies about correlation between baPWV and acute ischemic stroke currently .The present ar‐ticle aimed at expounding predictive value of baPWV for early prognosis in patients with acute ischemic stroke .
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Exposure to low-dose radiation (LDR,mostly less than 100 mGy) may reduce the vulnerability of exposed tissues to subsequent high-dose radiation (HDR)-induced damage,a phenomenon known as adaptive responses,which occurs via mechanisms including anti-inflammation and anti-oxidation.Alzheimer's disease (AD) is a type of dementia that causes problems with memory,thinking,and behavior.Using the available literature,this review will examine whether there is any effect of LDR on AD.The available evidence shows that although LDR can alter the expression of some genes related to AD such as Apbb1,Lrp1,and Il1α,these alterations do not cause AD-like syndromes in animals,suggesting that LDR may also simultaneously upregulate several protective mechanisms that prevent the eventual development of AD.Furthermore,LDR seems capable of improving the symptoms of AD,as evidenced by the experience of an 81-year-old female AD patient.This patient was diagnosed with AD more than 10 years ago and gradually progressed to advanced AD in 2015,despite routine treatment.The patient then received about 12 computed tomography scans (about 40 mGy each) up until Nov.2017,which significantly improved her quality of life and reduced several AD symptoms.The improvement in this patient's medical condition led to a few recent clinical trials investigating the effects of LDR on AD.To date,there is no efficient therapy available for AD,thus whether exposure to LDR at 100 mGy can provide a preventive or therapeutic effect for AD is an important issue.If LDR is a potential treatment for AD,as suggested by this reported case,this non-invasive approach would also bear the merit that it would be unlikely to cause a significant radiation health risk,as the LDR could be delivered locally to the head without any impact on other organs.
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Objective To assess the lung protection effect of sevoflurane on adult cardiac surgery during cardiopulmonary bypass (CPB) using Meta-analysis. Methods The databases of Cochrane library, Embase, PubMed, Google scholar,CNKI,Wanfang and Weipu were comprehensively searched by computer up to December 2017 to obtain the published literature on randomised controlled trials(RCT)of sevoflurane for lung protection under CPB.Key words included extracorporeal circulation, cardiac surgery, pulmonary protection, sevoflurane and Meta-analysis. And then a separate quality assessment and data extraction for the selected literatures were carried out by two researchers. The Meta-analysis was performed via statistical software RevMan5.3.Results Eleven RCT literatures and 440 patients in total were selected in this study, in which, 220 cases were for the sevoflurane group and 220 cases were for the total intravenous anesthesia (TIVA)group.The analysis results showed that the application of sevoflurane could significantly reduce the levels of IL-6 (P=0.005)and IL-8(P=0.01)in the blood,and decrease postoperative tracheal intubation time in CPB group compared with those of TIVA group(P<0.001).However,there were no statistical differences in the level of tumor necrosis factor-α(TNF-α) (P=0.19), the alveolar-arterial differences for oxygen[P(A-a)O2](P=0.68) and the oxygenation index OI between two groups (P=0.31). Conclusion The application of sevoflurane during CPB could effectively reduce the levels of some inflammatory factors in blood and decrease the postoperative tracheal intubation time. However, there is no adequate evidence to prove the definite lung protection effect of sevoflurane on CPB.