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This study aimed to explore the molecular mechanism of Juanbi Qianggu Formula(JBQGF), an empirical formula formulated by the prestigious doctor in traditional Chinese medicine, in the treatment of rheumatoid arthritis based on network pharmacology and cell function experiments. The main active components and targets of JBQGF were obtained through Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP) and Encyclopedia of Traditional Chinese Medicine(ETCM), and the core targets underwent functional enrichment analysis and signaling pathway analysis. Cytoscape 3.6.0 was used to construct a visualized "active component-target-signaling pathway" network of JBQGF. After screening, nine potential pathways of JBQGF were obtained, mainly including G protein-coupled receptor signaling pathway and tyrosine kinase receptor signaling pathway. As previously indicated, the fibroblast growth factor receptor 1(FGFR1) signaling pathway was highly activated in active fibroblast-like synoviocytes(FLS) in rheumatoid arthritis, and cell and animal experiments demonstrated that inhibition of the FGFR1 signaling pathway could significantly reduce joint inflammation and joint destruction in collagen-induced arthritis(CIA) rats. In terms of the tyrosine kinase receptor signal transduction pathway, the analysis of its target genes revealed that FGFR1 might be a potential target of JBQGF for rheumatoid arthritis treatment. The biological effect of JBQGF by inhibiting FGFR1 phosphorylation was preliminarily verified by Western blot, Transwell invasion assay, and pannus erosion assay, thereby inhibiting matrix metalloproteinase 2(MMP2) and receptor activator of nuclear factor-κB ligand(RANKL) and suppressing the invasion of fibroblasts in rheumatoid arthritis and erosive effect of pannus bone. This study provides ideas for searching potential targets of rheumatoid arthritis treatment and TCM drugs through network pharmacology.
الموضوعات
Rats , Animals , Synoviocytes , Matrix Metalloproteinase 2/metabolism , Network Pharmacology , Receptor, Fibroblast Growth Factor, Type 1/therapeutic use , Arthritis, Rheumatoid/genetics , Signal Transduction , Fibroblasts , Drugs, Chinese Herbal/therapeutic useالملخص
Organ transplantation is an effective treatment for multiple end-stage diseases. In recent years, rapid progress has been made in the field of organ transplantation, which has been widely accepted and applied in clinical practice. However, low utilization rate of donors and high postoperative complications remain to be urgently resolved. Heat shock protein (HSP) is a category of protein family induced by heat shock or other stressors. Upon stress stimulation, HSP plays an anti-inflammation, anti-oxidation and anti-apoptosis role in mitigating the stress-induced damage. HSP is also involved in the processes of promoting immune response and anti-rejection, etc. Organ transplantation, as a stress stimulus, could induce HSP to function in the process of organ transplantation through many patterns, thereby alleviating the allograft damage, improving the utilization rate of donors and prolonging the postoperative survival of recipients. In this article, research status on the role of HSP in lung transplantation, heart transplantation, liver transplantation and kidney transplantation were reviewed, aiming to provide reference for donor protection of organ transplantation and treatment of postoperative complications.
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Purpose@#The perception of faculty members about an individually tailored, flexible-length, outcomes-based curriculum for undergraduate medical students was studied. Their opinion about the advantages, disadvantages, and challenges was also noted. This study was done to help educational institutions identify academic and social support and resources required to ensure that graduate competencies are not compromised by a flexible education pathway. @*Methods@#The study was done at the International Medical University, Malaysia, and the University of Lahore, Pakistan. Semi-structured interviews were conducted from 1st August 2021 to 17th March 2022. Demographic information was noted. Themes were identified, and a summary of the information under each theme was created. @*Results@#A total of 24 (14 from Malaysia and 10 from Pakistan) faculty participated. Most agreed that undergraduate medical students can progress (at a differential rate) if they attain the required competencies. Among the major advantages mentioned were that students may graduate faster, learn at a pace comfortable to them, and develop an individualized learning pathway. Several logistical challenges must be overcome. Providing assessments on demand will be difficult. Significant regulatory hurdles were anticipated. Artificial intelligence (AI) can play an important role in creating an individualized learning pathway and supporting time-independent progression. The course may be (slightly) cheaper than a traditional one. @*Conclusion@#This study provides a foundation to further develop and strengthen flexible-length competency-based medical education modules. Further studies are required among educators at other medical schools and in other countries. Online learning and AI will play an important role.
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@#Objective To analyze the risk factors for esophagogastric anastomotic leakage (EGAL) after esophageal cancer surgery, and to establish a risk prediction model for early prevention and treatment. Methods Clinical data of patients undergoing esophagectomy in our hospital from January 2013 to October 2020 were retrospectively analyzed. The independent risk factors for postoperative EGAL were analyzed by univariate and multivariate logistic regression analyses, and a clinical nomogram prediction model was established. According to whether EGAL occurred after operation, the patients were divided into an anastomotic fistula group and a non-anastomotic fistula group. Results A total of 303 patiens were enrolled, including 267 males and 36 females with a mean age of 62.30±7.36 years. The incidence rate of postoperative EGAL was 15.2% (46/303). The multivariate logistic regression analysis showed that high blood pressure, chronic bronchitis, peptic ulcer, operation way, the number of lymph node dissected, anastomotic way, the number of intraoperative chest drainage tube, tumor location, no-supplementing albumin in the first three days after operation, postoperative pulmonary infection, postoperative use of bronchoscope were the independent risk factors for EGAL after esophageal cancer surgery (P<0.05). A prognostic nomogram model was established based on these factors with the area under the receiver operating characteristic curve of 0.954 (95%CI 0.924-0.975), indicating a high predictive value. Conclusion The clinical prediction model based on 11 perioperative risk factors in the study has a good evaluation efficacy and can promote the early detection, diagnosis and treatment of EGAL.
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@#Objective To systematically review risk factors for esophagogastric anastomotic leakage (EGAL) after esophageal cancer surgery for adults to provide theoretical basis for clinical prevention and treatment. Methods PubMed, Web of Science, The Cochrane Library, WanFang Data, VIP, CNKI and CBM were searched from inception to January 2020 to collect case control studies and cohort studies about risk factors for EGAL after esophageal cancer surgery. Two reviewers independently screened literature, extracted data and assessed risk of bias of included studies, and then, meta-analysis was performed by using RevMan 5.3 software. Results A total of 33 studies were included, including 19 case-control studies and 14 cohort studies, all of which had a Newcastle-Ottawa Scale (NOS)≥6. There were 26 636 patients, including 20 283 males and 6 353 females, and there were 9 587 patients in China and 17 049 patients abroad. The results of meta-analysis showed that the following factors could increase the risk for EGAL (P≤0.05), including patient factors (18): age, sex, body mass index (BMI), smoking history, smoking index (≥400), alcohol history, digestive tract ulcer, respiratory disease, lower ratio of forced expiratory volume in one second to forced vital capacity (FEV1/FVC), chronic obstructive pulmonary disease (COPD), coronary atherosclerosis, peripheral vascular disease, arrhythmia, diabetes, hypertension, cerebrovascular disease, celiac trunk calcification and descending aortic calcification; preoperative factors (6): abnormal liver function, renal insufficiency, American Society of Anesthesiologists (ASA) grading, neoadjuvant radiotherapy and preoperative albumin<35 g/L, preoperative lower albumin; intraoperative factors (7): retrosternal route, cervical anastomosis, thoracoscopic surgery, operation time≥4.5 h, tubular stomach, upper segment tumor, splenectomy; postoperative factors (5): respiratory failure, postoperative arrhythmia, use of fiberoptic bronchoscopy, pulmonary infection, deep venous thrombosis. Neoadjuvant chemotherapy could reduce the risk for postoperative EGAL (P<0.05). However, age≥60 years, upper gastrointestinal inflammation, diffusing capacity for carbon monoxide (DLCO%), thoracic surgery history, abdominal surgery history, glucocorticoid drugs history, neoadjuvant chemoradiotherapy, anastomotic embedding, end-to-end anastomosis, hand anastomosis, intraoperative blood loss and other factors were not significantly correlated with EGAL. Conclusion Current evidence suggests that the risk factors for postoperative EGAL include age, sex, BMI, smoking index, alcohol history, peptic ulcer, FEV1/FVC, COPD, diabetes, ASA grading, neoadjuvant radiotherapy, preoperative albumin<35 g/L, cervical anastomosis, thoracoscopic surgery, operation time≥4.5 h, tubular stomach, upper segment tumor, intraoperative splenectomy, postoperative respiratory failure, postoperative arrhythmia and other risk factors. Neoadjuvant chemotherapy may be the protection factor for EGAL. Due to limited study quality, more high quality studies are needed to verify the conclusion.
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Chemical fractionation of the n-BuOH partition, which was generated from the EtOH extract of the flower buds of Tussilago farfara, afforded a series of polar constituents including four new sesquiterpenoids (1-4), one new sesquiterpenoid glucoside (5) and one known analogue (6) of the eudesmane type, as well as five known quinic acid derivatives (7-11). Structures of the new compounds were unambiguously characterized by detailed spectroscopic analyses, with their absolute configurations being established by X-ray crystallography, electronic circular dichroism (ECD) calculation and induced ECD experiments. The inhibitory effect of all the isolates against LPS-induced NO production in murine RAW264.7 macrophages was evaluated, with isochlorogenic acid A (7) showing significant inhibitory activity.
الموضوعات
Animals , Mice , Flowers/chemistry , Glucosides/pharmacology , Sesquiterpenes/pharmacology , Sesquiterpenes, Eudesmane/pharmacology , Tussilago/chemistryالملخص
OBJECTIVE@#To investigate the cardioprotective effect of Danqi Tablet (DQT, ) on ischemic heart model rats and the regulative effect on energy metabolism through peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α).@*METHODS@#Rat ischemic heart model was induced by ligation of left anterior descending coronary artery. Totally 40 Sprague-Dawley rats were randomly divided into sham group, model group, DQT group (1.5 mg/kg daily) and trimetazidine (TMZ) group (6.3 mg/kg daily) according to a random number table, 10 rats in each group. Twenty-eight days after continuous administration, cardiac function was assessed by echocardiography and the structures of myocardial cells were observed by hematoxylin-eosin staining. The level of adenosine triphosphate (ATP) in myocardial cells was measured by ATP assay kit. Expressions level of key transcriptional regulators, including PGC-1α, Sirtuin 1 (SIRT1), AMP-activated protein kinase (AMPK), and downstream targets of PGC-1α, such as mitofusin 1 (MFN1), mitofusin 2 (MFN2) and superoxide dismutase 2 (SOD2) were measured by Western blot. Expression level of PGC-1α was examined by immunohistochemical staining.@*RESULTS@#The rat ischemic heart model was successfully induced and the heart function in model group was compromised. Compared with the model group, DQT exerted cardioprotective effects, up-regulated the ATP production in myocardial cells and inhibited the infiltration of inflammatory cells in the margin area of infarction of the myocardial tissues (P<0.01). The expressions of PGC-1α, SIRT1 and AMPK were increased in the DQT group (all P<0.05). Furthermore, the downstream targets, including MFN1, MFN2 and SOD2 were up-regulated (P<0.05 or P<0.01). Compared with the TMZ group, the expression levels of PGC-1α, MFN1 and SOD2 were increased by DQT treatment (P<0.05 or P<0.01).@*CONCLUSION@#DQT regulated energy metabolism in rats with ischemic heart model through AMPK/SIRT1 -PGC-1α pathway. PGC-1α might serve as a promising target in the treatment of ischemic heart disease.
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This study was aimed to determine the effect of acute cerebral ischemia on the protein expression level of silent mating type information regulator 2 homolog 3 (Sirt3) in the neurons and clarify the pathological role of Sirt3 in acute cerebral ischemia. The mice with middle cerebral artery occlusion (MCAO) and primary cultured rat hippocampal neurons with oxygen glucose deprivation (OGD) were used as acute cerebral ischemia models in vivo and in vitro, respectively. Sirt3 overexpression was induced in rat hippocampal neurons by lentivirus transfection. Western blot was utilized to measure the changes in Sirt3 protein expression level. CCK8 assay was used to detect cell viability. Immunofluorescent staining was used to detect mitochondrial function. Transmission electron microscope was used to detect mitochondrial autophagy. The results showed that, compared with the normoxia group, hippocampal neurons from OGD1 h/reoxygenation 2 h (R2 h) and OGD1 h/R12 h groups exhibited down-regulated Sirt3 protein expression levels. Compared with contralateral normal brain tissue, the ipsilateral penumbra region from MCAO1 h/reperfusion 24 h (R24 h) and MCAO1 h/R72 h groups exhibited down-regulated Sirt3 protein expression levels, while there was no significant difference between the Sirt3 protein levels on both sides of sham group. OGD1 h/R12 h treatment damaged mitochondrial function, activated mitochondrial autophagy and reduced cell viability in hippocampal neurons, whereas Sirt3 over-expression attenuated the above damage effects of OGD1 h/R12 h treatment. These results suggest that acute cerebral ischemia results in a decrease in Sirt3 protein level. Sirt3 overexpression can alleviate acute cerebral ischemia-induced neural injuries by improving the mitochondrial function. The current study sheds light on a novel strategy against neural injuries caused by acute cerebral ischemia.
الموضوعات
Animals , Mice , Rats , Brain Ischemia , Down-Regulation , Infarction, Middle Cerebral Artery , Mitochondria , Neurons/metabolism , Reperfusion Injury , Sirtuin 3/metabolism , Sirtuinsالملخص
@#How to effectively repair esophageal fistulas, caused by esophageal perforation, rupture and anastomotic leakage after esophagectomy has always been a key problem for the digestive surgeon. Although there are many clinical treatment methods, the therapeutic effect is still completely unsatisfactory, especially when severe mediastinal purulent cavity infection is associated with the esophageal fistula. In recent years, foreign centers have promoted a new minimally invasive endoscopic treatment technology to repair the esophageal fistula, endoscopic vacuum-assisted closure therapy, with significantly curative effect. In this article, we will review the specific operation, advantages and disadvantages, as well as the clinical efficacy of endoscopic vacuum-assisted closure therapy in treating the esophageal fistulas, to provide a new therapeutic technique for esophageal fistulas and expand the new field of minimally invasive endoscopic therapy.
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Objective@#: An important factor during pituitary adenoma surgery is to preserve pituitary stalk (PS) as this plays a role in reduction of the risk of postoperative diabetes insipidus. The hypothalamic-hypophyseal tract (HHT) projects through the PS to the posterior pituitary gland. To reconstruct white matter fiber pathways, methods like diffusion tensor imaging (DTI) tractography have been widely used. In this report we attempted to predict the position of PS using DTI tractography and to assess its intraoperative correlation during surgery of pituitary adenomas. @*Methods@#: DTI tractography was used to tract the HHT in nine patients before craniotomy for pituitary adenomas. The DTI location of the HHT was compared with the PS position identified at the time of surgery. DTI fiber tracking was carried out in nine patients prior to the planned craniotomy for pituitary adenomas. In one patient, the PS could not be identified during the surgery. In the other eight patients, a comparison was made between the location of the HHT identified by DTI and the position of the PS visualized at the time of surgery. @*Results@#: The position of the HHT identified by DTI showed consistency with the intraoperative position of the PS in seven patients (88.9% concordance). @*Conclusion@#: This study shows that DTI can identify the position of the HHT and thus the position of the PS with a high degree of reliability.
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Purpose@#Direct student involvement in quality processes in education has been suggested to encourage shared responsibilities among faculty and students. The objectives of this study were to explore undergraduate health professions students’ understanding of quality assurance (QA) in education, and identify the challenges and enablers for student involvement in an Asian context. @*Methods@#Twenty semi-structured interviews were conducted among medical, dentistry, and pharmacy students in a Malaysian University. The interviews were audio-recorded, transcribed verbatim, and thematically analyzed to understand the students’ perspectives of QA in education. @*Results@#The participants recognized the importance of QA towards ensuring the quality of their training, which will consequently impact their work readiness, employability, and quality of healthcare services. Academic governance, curriculum structure, content and delivery, faculty and student quality, teaching facilities, and learning resources were indicated as the QA areas. The challenges for students’ involvement included students’ attitude, maturity, and cultural barrier. To enhance their buy-in, clear objectives and impact, efficient QA mechanism, and recognition of students’ contribution had been suggested. @*Conclusion@#The findings of this study support student-faculty partnership in QA processes and decision making.
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The active ingredient of Ge Tong Tong Luo Capsule is the total flavonoids of Pueraria lobata, which mainly consists of puerarin, daidzein, daidzein-4V and other components. In the treatment of cerebral infarction, Ge Tong Tong Luo Capsule and its main pharmacological components have shown to inhibit the progression of atherosclerotic plaque, scavenge oxygen free radicals, anti-platelet aggregation, and inhibit neuronal apoptosis. In terms of adverse events, most of the studies were obvious adverse reactions caused by drugs. In rare studies, although there were adverse events such as palpitation and dry throat, they were relieved without treatment. This article introduces the pharmacological effects, clinical efficacy and adverse reactions of Ge Tong Tong Luo Capsule and its main pharmacological components, and provides a reference for clinical safe and rational drug use.
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OBJECTIVE@#To observe the effect of temperature contrast injection procedure on prevention and reduction of bone cement leakage in vertebroplasty (PVP).@*METHODS@#The clinical data of 42 patients(48 vertebral bodies) with osteoporotic vertebral compression fractures(OVCFs) treated from July 2014 to July 2018 were retrospectively analyzed. There were 19 males and 23 females, aged from 62 to 80 years old with an average of 72 years. The vertebral fracture segment was T₈-L₅, including 30 lumbar vertebrae and 18 thoracic vertebrae. The course of the disease ranged from 3 d to 2 months. Twenty cases (20 vertebral bodies) were treated by single vertebroplasty (group A) and 22 cases (28 vertebral bodies) were treated by temperature contrast injection procedure(group B). The operative time, amount of bone cement injection, VAS score at 3 days after surgery, leakage rate and refracture rate were compared between two groups.@*RESULTS@#The operative time, amount of bone cement injection and VAS score at 3 days after surgery in group B were (40.05±7.78) min, (3.93±0.19) ml, (3.55±0.74) points, respectively, and in group A were(38.90±6.81) min, (4.03±0.24) ml, (4.05±1.00) points, there was no significant difference between two groups(>0.05). The leakage rate in group B was lower than that in group A (9.1% vs 40.0%, 0.05).@*CONCLUSIONS@#Temperature contrast injection procedure is an effective method to reduce the bone cement leakage in vertebroplasty.
الموضوعات
Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Bone Cements , Fractures, Compression , Osteoporotic Fractures , Retrospective Studies , Spinal Fractures , Temperature , Treatment Outcome , Vertebroplastyالملخص
<p><b>Background</b>Measuring total serum calcium is important for the diagnosis of diseases. Currently, results from commercial kits for calcium measurement are variable. Generally, the performance of serum calcium measurements is monitored by external quality assessment (EQA) or proficiency testing schemes. However, the commutability of the EQA samples and calibrators is often unknown, which limits the effectiveness of EQA schemes. The aim of this study was to evaluate the bias of serum calcium measurements and the commutability of processed materials.</p><p><b>Methods</b>Inductively coupled plasma mass spectrometry was applied as a comparative method, and 14 routine methods were chosen as test methods. Forty-eight serum samples from individual patients and 25 processed materials were quantified. A scatter plot was generated from patient samples, and 95% prediction intervals were calculated to evaluate the commutability of the processed materials and measurement bias at three concentration levels was used to determine the accuracy of routine assays.</p><p><b>Results</b>All assays showed high precision (total coefficient of variation [CV] <2.26%) and correlation coefficients (r > 0.99). For all assays, the mean bias for the 48 patient samples ranged from -0.13 mmol/L to 0.00 mmol/L (-5.61-0.01%), and the ranges for the three concentrations were -0.10-0.04 mmol/L (-5.71-2.35%), -0.14--0.01 mmol/L (-5.80--0.30%), and -0.19-0.04 mmol/L (-6.24-1.22%). The EQA samples, calibrators, and animal sera exhibited matrix effects in some assays; human serum pools were commutable in all assays; certificate reference materials were commutable in most assays, and only GBW09152 exhibited a matrix effect in one assay; and aqueous reference materials exhibited matrix effects in most assays.</p><p><b>Conclusions</b>Biases for most assays were within the acceptable range, although the accuracy of some assays needs improvement. Human serum pools prepared from patient samples were commutable, and the other tested materials exhibited a matrix effect.</p>
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OBJECTIVES@#To analyze the relationship between the suicide method and the sex, age, education background and cause of suicide to provide reference for the forensic identification of suicide.@*METHODS@#After scene investigation, external body examination, autopsy and case investigation, 124 identified suicide cases which happened in recent three years in Wuhua district in Kunming were collected. Analytical methods as chi-square test and descriptive statistics were performed by SPSS 22.0.@*RESULTS@#In all the suicide cases, male to female ratio was 1.53∶1. The suicide methods were mainly fatal fall, hanging and drowning. The ratio of local to non-native residents was 1∶1. The suicide rate in the people with primary school or junior middle school education level was highest. The group of >10-50 years tended to choose fatal fall suicide and people over 60 years were more likely to choose hanging. People with different academic background tended to choose fatal fall suicide. The suicide methods as fatal fall and hanging were chosen because of mental and physical diseases and economic problems, while the suicides with emotional problems were more likely to choose fatal fall and poisoning.@*CONCLUSIONS@#Suicide belongs to a kind of complex cases. For the cases of suspected suicide, complete exploration and overall consideration should be done to determine the nature of cases based on comprehensive analysis of all the influence factors.
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Adolescent , Adult , Aged , Child , Female , Humans , Male , Middle Aged , Young Adult , Age Distribution , Autopsy , Cause of Death , China/epidemiology , Drowning/psychology , Incidence , Mental Disorders/psychology , Sex Distribution , Suicide/statistics & numerical dataالملخص
Myocardial fibrosis (MF) is an important pathological change involved in the progress from myocardial infarction (MI) to heart failure(HF). Metabolic disorder of arachidonic acid (AA) in cardiomyocytes plays an important role in process of MF. Fufang Danshen tablets is a traditional Chinese medicine (TCM), which showed significant effect on coronary heart diseases and anti-MF. However, the underlying mechanism of anti-MF remains unclear. In this study, HF animal model of myocardial infarction was established by ligation of left anterior descending coronary artery. The heart function of rats in each group was evaluated by echocardiography and hemodynamic measurement. Histological examination, TUNEL and Western blot were used to detect the levels of MF and proteins related to AA metabolism. As a result, MI significantly decreased the levels of ejection fraction (EF), ejection fraction (FS) and left ventricular systolic pressure (LVSP), and these decreases were significantly improved by the treatment of Fufang Danshen tablets. Besides, Fufang Danshen tablets treatment down-regulated the levels of creatine kinase-MB (CK-MB) and lactate dehydrogenase (LDH) in serum. HE, Masson and TUNEL staining results showed that Fufang Danshen tablets treatment could inhibit the inflammatory cells infiltration and attenuate the fibrosis and apoptosis to exert cardioprotective effect. Western blot indicated that Fufang Danshen tablets treatment down-regulated the expressions of AT₁, MMP2, MM9, while up-regulated the expression of AT₂ to inhibit MF. Further mechanism study indicated that Fufang Danshen tablets inhibited MF by down-regulated the expressions of AA metabolism, such as PLA2, P450, COX2 and 5-LOX. In summary, Fufang Danshen tablets can effectively inhibit MF in the ischemic area after MI in rats. The mechanism is related to the regulation of AT₁-mediated PLA2-COX2 metabolic pathway.
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Objective To observe the clinical efficacy of modified Yiqi Shengjiang Decoction for chronic heart failure (CHF) and its effects on BNP and LP-PLA2. Methods Totally 100 cases of patients with CHF were randomly divided into treatment group and control group, with 50 cases in each group. The control group received basic treatment, and the treatment group was treated with modified Yiqi Shengjiang Decoction on the basis of control group, one dosage per day, twice a day, orally, for 4 weeks. The curative effect of heart function grading and curative effect of TCM symptoms of the two groups, the changes of plasma BNP and LP-PLA2 levels were observed. Safety indicators were monitored. Results The total effective rate of cardiac function classification was 88% (44/50) in the treatment group and 68% (34/50) in the control group, with the treatment group much better than the control group (P<0.05); the total effective rate of TCM symptom efficacy was 90% (45/50) in the treatment group and 74% (37/50) in the control group, with the treatment group much better than the control group (P<0.05). The BNP and LP-PLA2 levels in the treatment group were lower than the control group after treatment, with statistical significance (P<0.05). No adverse reactions were observed in both groups, with no abnormalities in blood, urine, liver and kidney function. Conclusion Modified Yiqi Shengjiang Decoction combined with Western medicine has obvious advantages in the treatment of CHF in improving patients' heart function, and reducing plasma BNP and LP-PLA2 levels.
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Hydrogel nanoparticles (NPs) were synthesized by precipitation polymerization method with N-isopropyl acrylamide (NIPAm), acrylic acid (Aac), N-tert butyl acrylamide (tBAM) and N,N'-methylene bisacrylamide(Bis) as thermosensitive monomer,negative monomer,hydrophobic monomer and crosslinker, respectively. The morphology of the resulting NPs was characterized by scanning electron microscopy(SEM),and the size and the particle size distribution were investigated by dynamic light scattering (DLS). The dynamics test was also carried out to investigate adsorption property of NPs. The results showed that NPs was spherical with uniform particle size and narrow distribution. NPs had the best adsorption performance to lysozyme when the monomer molar ratio was optimized to Aac 20%,tBAM 40%,NIPAm 38% and Bis 2%. Meanwhile, when the particle size of NPs decreased from 386. 20 nm to 77. 25 nm, the adsorption capacity increased gradually. The adsorption rate could reach up to 67.8% within 5 minutes. The thermosensitive of NPs provided a new candidate for the adsorption and separation of lysozyme with good reusability.
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Objective To investigate both in mechanism of hyperoxia-induced acute lung injury (HALI) by vivo experiment,to observe the Bruton' s tyrosine kinase (Btk) and nuclear factor kappa B (NF-κB) signals expression level.Methods Total of 72 healthy male Kunming mice were randomly (random number) divided into four groups:air control group,hyperoxia exposure 3 days group (H3d group),hyperoxia exposure 3 days + inhibitor group (H3d + Ⅰ group) and inhibitor groups.Then the pathological changes of lung tissues were observed under light microscope;The total protein content (TP) of bronchoalveolar lavage fluid (BALF) and wet/dry weight ratio (W/D) of lung were detected;The protein expression of Btk,p-Btk,pNF-κB p65 were mersured by Western blot;tlhe mRNA level of IL-6 was determined by real-time polymerase chain reaction (qRT-PCR);the level of monocyte chemoattractant protein-1 (MCP-1) in serum was detected by enzyme-linked immunosorbent assay (ELISA).Statistcal significance was determined by 1-way ANOVA.Results There were no significant difference in the data between the control group and the inhibitor group (P > 0.05).The pathological injury in light microscope,content of total protein in BALF,W/D ratio of lung tissues in H3d group were significantly higher than H3d + Ⅰ group (Respectively P =O.002,P =0.000).Western blot analysis showed that expression of Btk,p-Btk,pNF-κB p65 in H3d group were significantly higher than those in H3d + Ⅰ group (Respectively P =0.002,P =0.013,P =0.000).RT-qPCR results showed that the expression of IL-6 mRNA in H3d group were significantly higher than control group (P =0.004),inhibitor group (P =0.000) and H3d + Ⅰ group (P =0.021).In addition,The serum MCP-1 levels in H3d group were higher markely than the control group (P =0.002),inhibitor group (P =0.000) and H3d + Ⅰ group (P =0.009).The correlation analysis showed that pNF-κB p65 were positively correlated wiht Btk and p-Btk (r =0.902 and 0.954,P < 0.01).Conclusions Btk may trigger the release of IL-6 and MCP-1 by mediating the signaling pathway of NF-κB in vivo study,which was most important in the occurrence of HALI.Therefore,inhibiting the Btk activity would alleviate the severity of lung injury effectively.
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<p><b>OBJECTIVE</b>To assess the effects of Qishen Granule (, QSG) on sarcoplasmic reticulum (SR) Cahandling in heart failure (HF) model of rats and to explore the underlying molecular mechanisms.</p><p><b>METHODS</b>HF rat models were induced by left anterior descending coronary artery ligation surgery and high-fat diet feeding. Rats were randomly divided into sham (n=10), model (n=10), QSG (n=12, 2.2 g/kg daily) and metoprolol groups (n=12, 10.5 mg/kg daily). The therapeutic effects of QSG were evaluated by echocardiography and blood lipid testing. Intracellular Caconcentration and sarco-endoplasmic reticulum ATPase 2a (SERCA2a) activity were detected by specifific assay kits. Expressions of the critical regulators in SR Cahandling were evaluated by Western blot and real-time quantitative polymerase chain reaction.</p><p><b>RESULTS</b>HF model of rats developed ventricular remodeling accompanied with calcium overload and defective Carelease-uptake cycling in cardiomyocytes. Treatment with QSG improved contractive function, attenuated ventricular remodeling and reduced the basal intracellular Calevel. QSG prevented defective Caleak by attenuating hyperphosphorylation of ryanodine receptor 2, inhibiting expression of protein kinase A and up-regulating transcriptional expression of protein phosphatase 1. QSG also restored Cauptake by up-regulating expression and activity of SERCA2a and promoting phosphorylation of phospholamban.</p><p><b>CONCLUSION</b>QSG restored SR Cacycling in HF rats and served as an ideal alternative drug for treating HF.</p>