Multi-center Randomized Controlled Clinical Trial of Huangqi Injection Combined with Buzhong Yiqi Acupuncture in Treatment of Chronic Fatigue Syndrome with Qi Deficiency / 中国实验方剂学杂志

ObjectiveTo investigate the clinical efficacy of Huangqi injection combined with Buzhong Yiqi acupuncture in the treatment of chronic fatigue syndrome （CFS） with Qi deficiency and its effects on TCM syndromes， fatigue symptoms， serum superoxide dismutase （SOD）， malondialdehyde （MDA）， and oxidized low-density lipoprotein （ox-LDL） levels. MethodA total of 200 patients with CFS of Qi deficiency were randomly divided into a control group （100 cases） and an observation group （100 cases）. The control group was treated with vitamin B compounds， and the observation group was treated with Huangqi injection combined with Buzhong Yiqi acupuncture for two weeks. The scores of TCM syndromes， fatigue symptoms， levels of serum SOD， MDA， and ox-LDL and the incidence of adverse reactions were observed and compared before and after treatment in two groups. ResultAfter treatment， the total effective rate of the control group was 54.34% （50/92）， while that of the observation group was 88.54% （85/96）. The total effective rate of the observation group was higher than that of the control group （χ2=27.13，P<0.05）. Compared with those in the two groups before treatment， scores of fatigue self-assessment scale （FSAS）， physical fatigue and mental fatigue， and sleep/rest response scores of fatigue in the two groups after treatment were significantly decreased （P<0.05）. After treatment， scores of FSAS， physical fatigue and mental fatigue， and sleep/rest response scores of fatigue in the observation group were significantly decreased compared with those in the control group （P<0.05）. Compared with those in the two groups before treatment， TCM syndrome scores in the two groups after treatment were significantly decreased （P<0.05）. After treatment， TCM syndrome scores in the observation group were significantly decreased compared with those in the control group （P<0.05）. Compared with those in the two groups before treatment， MDA levels in the two groups were significantly decreased （P<0.05）， ox-LDL levels in the observation group were significantly decreased （P<0.05）， and SOD levels were significantly increased （P<0.05）. After treatment， compared with those in the control group， the serum MDA and ox-LDL levels in the observation group were significantly decreased （P<0.05）， and the serum SOD was significantly increased （P<0.05）. No serious adverse events or adverse reactions occurred during this clinical trial. ConclusionHuangqi injection combined with Buzhong Yiqi acupuncture has a good clinical curative effect in the treatment of CFS with Qi deficiency， which can effectively improve the fatigue symptoms of patients， increase the level of SOD， and reduce the level of serum MDA and ox-LDL. It is related to the production of antioxidants， inhibiting the production of lipid peroxides， and improving the body's ability to resist oxidative stress.

Long non-coding RNA alpha-2-macroglobulin antisense RNA 1 regulating oxidized low density lipoprotein-induced human brain microvascular endothelial cell damage by targeting microRNA-106b-5p / 解剖学报

Objective To investigate the effect of long non-coding RNA (lncRNA) alpha-2-macroglobulin antisense RNA 1 (A2M-AS1) targeting microRNA (miR) -106b-5p on oxidized low-density lipoprotein (ox-LDL) -induced injury of human brain microvascular endothelial cells. Methods Human brain microvascular endothelial cells (ox-LDL group) were induced by ox-LDL, normal cultured cells were control group (Ctrl); A2M-AS1 overexpression (pcDNAA2M-AS1 group), empty vector (pcDNA group), miR-106b-5p inhibitor (anti-miR-106b-5p group), negative control (anti-miR-NC group), pcDNA-A2M-AS1 with control mimic NC (miR-NC group), pcDNA-A2M-AS1 with miR-106b-5p mimic (miR-106b-5p mimics group) were transfected into cells and treated with ox-LDL, n = 9. Real-time PCR was used to detect the expression levels of A2M-AS1 and miR-106b-5p; Kits were used to detect malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT)); Flow cytometry and TUNEL detected apoptosis; Dual luciferase reporter gene assay detected A2M-AS1 and miR-106b-5p targeting; Western blotting detected Bcl-2 and Bax protein expression. Results Compared with the Ctrl group, the expression level of A2M-AS1 in the ox-LDL group decreased, and the activity of SOD and CAT and the protein level of Bcl-2 decreased (P<0.05), while the expression level of miR-106b-5p and the level of MDA increased (P<0.05), and the rate of apoptosis and the protein level of Bax increased (P<0.05). Overexpressing A2M-AS1 or interfering with miR-106b-5p decreased the MDA level, apoptosis rate and Bax protein level after ox-LDL-induced cells, and increased SOD, CAT activity and Bcl-2 protein level (P<0.05). A2M-AS1 targeted miR-106b-5p; upregulation of miR-106b-5p reversed the effect of overexpressed lncRNA A2M-AS1 on ox-LDL-induced injury of human brain microvascular endothelial cells (P < 0.05). Conclusion A2M-AS1 attenuates ox-LDL-induced injury of human brain microvascular endothelial cells by targeting miR-106b-5p.

Mechanism of scutellarein inhibiting foaming of macrophages by promoting cholesterol efflux pathway / 中国药理学通报

Aim To investigate the effects of scutellarein on the macrophage foam cell formation and cholesterol efflux, and the underlying mechanism. Methods THP-1 cells were differentiated with PMA, and the cell viability was detected by MTT assays. The effects of scutellarein on the cholesterol efflux and macrophage foam cell formation were evaluated by using NBD-la-beled cholesterol and the cholesterol detection kit. The effects of scutellarein on the activation of PPARγ-LXRα-ABCA1 signaling pathway were determined by molecular docking, ELISA, dual-luciferase reporter and Western blot. The effects of PPARγ knowdown on scutellarein-induced cholesterol efflux and inhibiting macrophage foaming were analyzed by siRNA interference. Results Scutellarein dose-dependently inhibited oxLDL-induced cholesterol accumulation, accelerated cholesterol efflux and significantly increased the protein expression of LXRα and ABCA1. At the same time, scutellarein could bind PPARγ and initiate its downstream LXRa-ABCAl signaling pathway. In addition, gene silencing of PPARγ not only significantly inhibited scutellarein-induced LXRα-ABCA1 signaling pathway and cholesterol efflux, but also reversed the inhibitory effect of scutellarein on macrophage foaming. Conclusions Scutellarein could promote the cholesterol efflux by activating PPARγ and initiating the downstream LXR-ABCA1 signaling pathway, thereby prevent the macrophage foam cell formation.

Prediction of poor prognosis in patients with acute cerebral infarction / 中国医师进修杂志

Objective:To explore the predictive values of serum monocyte chemoattractant protein-1 (MCP-1), high mobility protein B1 (HMGB1), adiponectin (APN) and oxidized low density lipoprotein (ox-LDL) levels on poor prognosis of patients with acute cerebral infarction(ACI).Methods:One hundred and sixty-fivepatients with ACI in Zibo Hospital, Shandong Guoxin Nursing Group from October 2018 to December 2020 were selected as the observation group, and 147 healthy people in the same period were selected as the normal control group. The levels of serum MCP-1, HMGB1, APN and ox-LDL were detected. In addition, the observation group was followed up for 3 months after discharge, and the observation group was divided into good prognosis group and poor prognosis group by modified Rankin Scale score. The levels of serum MCP-1, HMGB1, APN and ox-LDL between the poor prognosis group and the good prognosis group were compared. The influencing factors of poor prognosis in patients with ACI and the predictive value of serum MCP-1, HMGB1, APN and ox-LDL levels on poor prognosis were analyzed by Logistic multiple regression analysis and receiver operating characteristic (ROC) curve.Results:The levels of serum MCP-1, HMGB1 and ox-LDL in the observation group were higher than those in the normal control group: (322.61 ± 65.27) ng/L vs. (163.18 ± 15.12) ng/L, (6.61 ± 3.54) μg/L vs. (2.90 ± 0.41) μg/L, (481.11 ± 177.67) mg/L vs. (247.47 ± 27.13) mg/L; but the level of serum APN was lower than that in the normal control group: (10.63 ± 3.80) μg/L vs. (17.65 ± 2.87) μg/L, there were statistical differences ( P<0.05). After 3 months of follow-up, the incidence rate of poor prognosis in the observation group was 35.15%(58/165). The serum levels of MCP-1, HMGB1 and ox-LDL in the poor prognosis group were higher than those in the good prognosis group: (372.15 ± 71.33) ng/L vs. (295.76 ± 42.23) ng/L, (9.74 ± 3.96) μg/L vs. (4.91 ± 1.62) μg/L, (631.03 ± 196.84) mg/L vs. (399.85 ± 95.07) mg/L; but the serum APN level was lower than that in the good prognosis group: (7.62 ± 2.83) μg/L vs. (12.27 ± 3.22) μg/L, there were statistical differences ( P<0.05). The results of Logistic multiple regression analysis showed that age, hypertension, hyperlipidemia, infarct volume, nerve function defect score, time from onset to treatment and MCP-1, HMGB1, APN and ox-LDL levels were the influencing factors of poor prognosis in patients with ACI ( P<0.05). The results of ROC curve analysis showed that the sensitivity and area under the curve of serum MCP-1, HMGB1, APN and ox-LDL levels in combined predicting the poor prognosis were 98.28% and 0.954, which were higher than the single index evaluation ( P<0.05). Conclusions:The serum levels of MCP-1, HMGB1 and ox-LDL are closely related to the prognosis of ACI patients, and all of them have a certain predictive value for the poor prognosis of patients, but the combined prediction efficiency of four items is more higher.

LOX-1 Regulation in Anti-atherosclerosis of Active Compounds of Herbal Medicine: Current Knowledge and the New Insight / 中国结合医学杂志

Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) have recently been identified to be closely related to the occurrence and development of atherosclerosis (AS). A growing body of evidence has suggested Chinese medicine takes unique advantages in preventing and treating AS. In this review, the related research progress of AS and LOX-1 has been summarized. And the anti-AS effects of 10 active components of herbal medicine through LOX-1 regulation have been further reviewed. As a potential biomarker and target for intervention in AS, LOX-1 targeted therapy might provide a promising and novel approach to atherosclerotic prevention and treatment.

Guanxinning Tablet and their active substances alleviate ox-LDL-induced endothelial cell injury / 药学学报

This study investigated the intervention effect of Guanxinning Tablet on human umbilical vein endothelial cells (HUVECs) injury induced by oxidized low density lipoprotein (ox-LDL), providing experimental basis for Guanxinning Tablet in the treatment of atherosclerosis-related diseases. Under the damage of HUVECs by ox-LDL, the cell viability was detected by CCK-8 (cell counting kit-8) assay; lactate dehydrogenase (LDH) in the cell culture supernatant was detected by the corresponding kit; the cell morphology of different groups was observed by common phase contrast microscope; reactive oxygen species (ROS) and NO levels in the cells were detected by DCFH-DA and DAF-FM DA probes, respectively; monocyte adhesion assay was used to detect the recruitment of THP-1 in HUVECs, and TMRM dye was used to detect the level of mitochondrial membrane potential; interleukin-6 (IL-6), intercellular adhesion molecule-1 (ICAM-1) and monocyte chemoattractant protein-1 (MCP-1) secretion in the cells was detected by ELISA assay. The results showed that Guanxinning Tablet had a concentration-dependent proliferative effect on HUVECs. Under the stimulation of 100 μg·mL-1 ox-LDL, the morphology of endothelial cells was significantly changed. At this time, NO level was significantly decreased, ROS level was significantly increased and accompanied by a decrease in mitochondrial membrane potential. The recruitment of THP-1 cells by endothelial cells and IL-6, ICAM-1 and MCP-1 were also significantly increased, resulting in oxidative stress and inflammatory injury. Guanxinning Tablet and its composed extracts could significantly improve cell morphology, increase NO level, decrease ROS production, and also reduce the secretion of inflammation-related proteins IL-6 and MCP-1. Salvia miltiorrhiza and Ligusticum striatum DC. have significant synergistic effects on NO. Among them, salvianolic acid B and salvianic acid A exerted the main effects, and the combined efficacy of salvianic acid A and ferulic acid was superior to that of single administration. The above results showed that Guanxinning Tablet and their active substances had the effects of improving endothelial basal function, resisting oxidative stress, and alleviating inflammatory injury, and Salvia miltiorrhiza and Ligusticum striatum DC. synergized, which may be related to their regulation of oxidative stress and inflammation and have application prospects in the treatment of atherosclerosis-related diseases.

Os Ácidos Graxos Poli-insaturados Ômega-6 e Ômega-3 Presentes nas Hemácias Exercem uma Influência Distinta sobre o Tamanho das Partículas de LDL e suas Alterações Estruturais / Red Blood Cells' Omega-6 and Omega-3 Polyunsaturated Fatty Acids Have a Distinct Influence on LDL Particle Size and its Structural Modifications

Resumo Fundamento Embora os ácidos graxos poli-insaturados ômega-3 e ômega-6 (AGPIs n-3 e n-6) tenham efeitos bem conhecidos sobre os fatores de risco de doenças cardiovasculares (DCV), ainda existe um conhecimento limitado sobre como eles afetam os indicadores de qualidade da LDL. Objetivo Avaliar as associações dos AGPIs n-3 e n-6 de hemácias com o tamanho da partícula da LDL, LDL-c pequena e densa (sdLDL-c) e com LDL eletronegativa [LDL(-)] em adultos com fatores de risco para DCV. Métodos Estudo transversal com 335 homens e mulheres de 30 a 74 anos com, pelo menos, um fator de risco cardiovascular. Foram realizadas análises de parâmetros bioquímicos, como glicose, insulina, HbA1c, proteína C reativa (PCR), perfil lipídico, subfrações de lipoproteínas, partícula eletronegativa de LDL [LDL(-)] e seu autoanticorpo, e os AGPIs n-3 e n- 6 de hemácias. Os testes t independente/teste de Mann-Whitney, ANOVA unidirecional/teste de Kruskal-Wallis e regressões lineares múltiplas foram aplicados. Todos os testes foram bilaterais e um valor de p inferior a 0,05 foi considerado estatisticamente significativo. Resultados A relação n-6/n-3 de hemácias foi associada ao aumento dos níveis de LDL(-) (β = 4,064; IC de 95% = 1,381 - 6,748) e sdLDL-c (β = 1,905; IC de 95% = 0,863 - 2,947), e redução do tamanho das partículas de LDL (β = -1,032; IC de 95% = -1,585 − -0,478). Individualmente, os AGPIs n-6 e n-3 apresentaram associações opostas com esses parâmetros, realçando os efeitos protetores do n-3 e evidenciando os possíveis efeitos adversos do n-6 na qualidade das partículas de LDL. Conclusão O AGPI n-6, presente nas hemácias, foi associado ao aumento do risco cardiometabólico e à aterogenicidade das partículas de LDL, enquanto o AGPI n-3 foi associado a melhores parâmetros cardiometabólicos e à qualidade das partículas de LDL.

Abstract Background While Omega-3 and omega-6 polyunsaturated fatty acids (n-3 and n-6 PUFAs) have established effects on cardiovascular disease (CVD) risk factors, little is known about their impacts on LDL quality markers. Objective To assess the associations of n-3 and n-6 PUFA within red blood cells (RBC) with LDL particle size, small dense LDL-c (sdLDL-c), and electronegative LDL [LDL(-)] in adults with CVD risk factors. Methods Cross-sectional study involving 335 men and women aged 30 to 74 with at least one cardiovascular risk factor. Analyses were conducted on biochemical parameters, such as glucose, insulin, HbA1c, C-reactive protein (CRP), lipid profile, lipoprotein subfractions, electronegative LDL particle [LDL(-)] and its autoantibody, and RBC n-3 and n-6 PUFAs. Independent t-test/Mann-Whitney test, one-way ANOVA/Kruskal-Wallis test, and multiple linear regressions were applied. All tests were two-sided, and a p-value of less than 0.05 was considered statistically significant. Results The RBC n-6/n-3 ratio was associated with increased LDL(-) (β = 4.064; 95% CI = 1.381 - 6.748) and sdLDL-c (β = 1.905; 95% CI = 0.863 - 2.947) levels, and reduced LDL particle size (β = -1.032; 95% CI = -1.585 − -0.478). Separately, n-6 and n-3 PUFAs had opposing associations with those parameters, reinforcing the protective effects of n-3 and showing the potential negative effects of n-6 on LDL particle quality. Conclusion RBC n-6 PUFA was associated with increased cardiometabolic risk and atherogenicity of LDL particles, while n-3 PUFA was associated with better cardiometabolic parameters and LDL particle quality.

Post-thoracotomy paraplegia after oxidized cellulose spinal compression

ABSTRACT Post-thoracotomy paraplegia after non-aortic surgery is an extremely uncommon complication. A 56-year-old woman presented with a 1-year history of progressive shortness of breath. Computed tomography revealed a locally advanced posterior mediastinal mass involving the ribs and the left neural foramina. Tumor excision with a left pneumonectomy was performed. Post-resection, bleeding was noted in the vicinity of the T4-T5 vertebral body, and the bleeding point was packed with oxidized cellulose gauze (Surgicel®). Postoperatively, the patient complained of bilateral leg numbness extending up to the T5 level, with bilateral paraplegia. An urgent laminectomy was performed, and we noted that the spinal cord was compressed by two masses of Surgicel® with blood clots measuring 1.5 × 1.5cm at T4 and T5 levels. The paraplegia did not improve despite the removal of the mass, sufficient decompression, and aggressive postoperative physiotherapy. Surgeons operating in fields close to the intervertebral foramen should be aware of the possible threat to the adjacent spinal canal as helpful hemostatic agents can become a preventable threat.

Uso de membrana de celulosa oxidada post-gingivectomía en hiperplasia gingival inducida por fenitoína / Use of oxidized cellulose regenerated post-gingivectomy on ginigival hyperplasia induced by phenytoin

Introducción: La hiperplasia gingival es una condición benigna caracterizada por el aumento de volumen de la encía. Algunos fármacos, factores genéticos, aparatología y placa dentobacteriana son factores que pueden inducir esta condición. Objetivo: Devolver la anatomía a la encía brindando una mejor estética y permitiendo una óptima higiene oral. Material y métodos: Paciente masculino de 20 años de edad con antecedentes de fenitoína presenta aumento de volumen en la encía. Resultados: Se obtuvieron resultados estéticos y funcionales satisfactorios con el tratamiento quirúrgico y el uso de membrana de celulosa oxidada. Conclusión: En el manejo de la hiperplasia gingival es importante el enfoque no quirúrgico como control de placa dentobacteriana y medidas de higiene del mismo paciente (AU)

Introduction: Gingival hyperplasia is a benign condition characterized for the grown on the gingival volume. Some drugs, genetic, orthodontic and dental plaque are some factors that can induce this condition. Objective: To return the gingival anatomy, providing a better aesthetic allowing also good oral hygiene. Material and methods: A male 20 years of age with medical history of phenytoin display grown on the gingival volume. Results: Aesthetic and functional results were achieved with the surgical treatment and the oxidized cellulose membrane. Conclusion: In the gingival hyperplasia management is important de non-surgical approach, as dental plaque control and oral hygiene of the patient (AU)

Effects of miR-195-5p on ox-LDL-induced vascular endothelial cell injury through regulating FBXW7 / 中国临床药理学与治疗学

AIM: To investigate the effect of miR-195-5p on ox-LDL-induced vascular endothelial cell injury and its mechanism. METHODS: The expression of miR-195-5p in HUVECs cells induced by ox-LDL was detected by RT-PCR. Cell proliferation, the expression of oxidative stress associated factors (MDA and LDH) and apoptosis were detected by CCK-8, ELISA and flow cytometry, respectively. The potential targets of miR-195-5p were determined by dual luciferase reporter assay. The expression of target protein in ox-LDL-induced HUVECs cells and the relationship between miR-195-5p and FBXW7 expression were detected by Western blotting. RESULTS: The expression of miR-195-5p in ox-LDL-induced HUVECs cells was significantly higher than that in normal HUVECs cells. Subsequently, miR-195-5p silencing in ox-LDL-induced HUVECs cells effectively promoted the proliferation of HUVECs cells, whereas suppressed the expression of oxidative stress associated factors (MDA and LDH) and apoptosis level. Luciferase reporter assay and Western blot results showed that miR-195-5p could directly target FBXW7 protein gene and negatively regulate its expression. Finally, miR-195-5p modulated the proliferation, oxidative stress and apoptosis of HUVECs cells induced by ox-LDL by regulating the expression of FBXW7. CONCLUSION: miR-195-5p is highly expressed in HUVECs cells induced by ox-LDL. In addition, miR-195-5p can aggravate ox-LDL-induced cytotoxicity, oxidative stress and apoptosis of HUVECs cells by inhibiting the expression of FBXW7.

Fucoxanthin suppresses OxLDL-induced inflammation via activation of Nrf2 and inhibition of NF-κB signaling

Objective: To explore the impact of fucoxanthin on oxidized low-density lipoprotein (OxLDL)-induced stress and inflammation in human endothelial cells and its underlying mechanisms. Methods: HUVECs were treated with OxLDL and/or fucoxanthin for a range of time points and concentrations. We evaluated the effects of fucoxanthin on OxLDL-induced HUVECs using the MTT assay, reactive oxygen species accumulation assay, ELISA, RT-PCR, immunofluorescence, and Western blotting. Results: Fucoxanthin enhanced the cell viability in a dose dependent manner after OxLDL exposure. Furthermore, fucoxanthin pretreatment significantly decreased OxLDL-induced reactive oxygen species production and prevented the activation of the nuclear factor kappa-B pathway, which led to substantial suppression of pro-inflammatory gene expressions. OxLDL-induced upregulation of interleukin-6, intercellular adhesion molecule-1, vascular cell adhesion molecule-1, interleukin-1β, monocyte chemotactic protein-1, cyclooxygenase-1, and tumor necrosis factor-α was significantly reduced by fucoxanthin. Conclusions: Fucoxanthin can inhibit OxLDL-induced vascular inflammation and oxidative stress in HUVECs by targeting Nrf2 signaling pathways.

Protective Mechanism of Youguiwan through AOPPs Regulating RAGE/ROS/NF-κB Axis and Wnt/β-catenin Signal in Rats with Adriamycin-induced Nephrotic Syndrome / 中国实验方剂学杂志

ObjectiveTo explore the effect of Youguiwan on the rats with adriamycin-induced nephrotic syndrome （NS） and its mechanism. MethodSD rats were randomly divided into a normal group， a model group， three Youguiwan low， medium， and high-dose groups， and a prednisone group. Rats in the model group were intravenously injected with adriamycin in the tail vein to induce the NS model. Rats in the Youguiwan low， medium， and high-dose groups were given 2.8， 5.6， 11.2 g·kg-1·d-1 of crude drugs， respectively， and rats in the prednisone group were given 6.3 mg·kg-1·d-1 of prednisone acetate. Each administration group was given continuous medicine for 6 weeks， and the normal group and model group were given an equal volume of normal saline. Bicinchoninic acid （BCA） assay was used to detect 24 h urine protein （24 h UP）. Automatic biochemical analyzer was used to detect serum urea nitrogen （BUN）， creatinine （SCr）， albumin （ALB）， total cholesterol （TC）， and triglyceride （TG） levels. Hematoxylin-eosin （HE） staining was used to observe renal tissue morphology， and kit was used to detect serum advanced oxidized protein products （AOPPs） and reactive oxygen species （ROS）. Western blot was used to detect the receptor of advanced glycation endproducts （RAGE） of renal tissue， nuclear factor-κB （NF-κB） phosphorylation levels， Wnt， and β-catenin protein expression. ResultAs compared with the normal group， 24 h UP， serum BUN， SCr， TC， TG， AOPPs， and ROS levels in the model group increased significantly （P<0.01）， whereas ALB decreased （P<0.01）. There were typical pathological injuries in the renal tissue， and the expressions of RAGE， phosphorylation（p）-NF-κB， Wnt1， and β-catenin protein were significantly increased （P<0.01）. As compared with the model group， the 24 h UP， serum BUN， SCr， TC， TG， AOPPs， and ROS levels of rats in the Youguiwan low， medium， and high-dose groups significantly reduced （P<0.01）， and ALB significantly increased （P<0.01）. The renal tissue damage was reduced， and the expressions of RAGE， p-NF-κB， Wnt1， and β-catenin protein were significantly decreased （P<0.01） in a dose-dependent manner. ConclusionYouguiwan improves the kidney injury of rats with adriamycin-induced NS. The mechanism may be related to the reduction of AOPPs level， inhibition of RAGE/ROS/NF-κB axis， and activation of Wnt/β-catenin signal.

Prevention of SSI in Cardiac Surgery by Using Intraoperative Measures for High-Risk Patients as Standard Precautions against Mediastinitis / 日本心臓血管外科学会雑誌

Background : Risk factors for surgical site infection (SSI) are thought to include poorly controlled diabetes mellitus, dialysis, and a long operating time, but patients without risk factors can also develop infection. Therefore, it is possible that SSI could be prevented by routinely using the precautions against SSI developed for high-risk patients. We investigated the route and pathogenetic mechanism of mediastinitis, which is the most frequent SSI after cardiac surgery. We hypothesized that mediastinitis occurred when the deep sternal marrow was contaminated by skin bacteria. Based on this hypothesis, we investigated the efficacy of various intraoperative prophylactic methods for preventing mediastinitis. Methods : We evaluated 658 patients undergoing cardiac surgery at our institution between April 2011 and July 2016. They were classified into two groups. Group C comprised 406 patients who received standard insertion of a sternal retractor after sternotomy. Group S was 252 patients in whom a retractor was inserted after covering the sternal marrow with oxidized cellulose hemostats and belt-like thin towels, with surplus parts of the towels being used to fill subcutaneous dead space at the superior and inferior margins of the midline wound. We investigated the following 10 risk factors for mediastinitis: diabetes (HbA1c≥7.5), renal failure (Cr≥2), smoking, obesity (BMI≥30), reoperation, urgent/emergency operation, intubation in the preoperative period, long operating time (≥8 h), reopening the chest for hemostasis, and coronary artery bypass grafting (CABG). Factors associated with mediastinitis were determined using univariate modeling analysis followed by multi-variate logistic regression analysis. Results : Mediastinitis occurred in 13 patients (2.0%). The significant risk factor for mediastinitis were urgent/emergency operation and CABG, but 1 patient had no risk factors. A univariate analysis showed statistical significance in CABG, presence of maneuver covering the sternal marrow, JapanSCORE-II in mortality and deep sternum infection (DSI). Reopening the chest for hemostasis, CABG, aortic aneurysm, plural risk factors, and JapanSCORE-II in DSI were identified as a risk factor by multiple logistic regression, not all factors showed a significant difference. Mediastinitis only occurred in group C, and it was significantly less frequent in group S with additional precautions against infection including propensity score matching analysis (p<0.05). Conclusion : When the bone marrow of the transected sternum was covered tightly to protect it from contamination by skin bacteria during cardiac surgery, the frequency of postoperative mediastinitis was significantly reduced.

Effect of Kudinoside D on ox-LDL-induced lipid accumulation and LPS-induced inflammation / 中国药理学通报

Aim To investigate the effects of Kudino- side D on lipid accumulation induced by oxidized low density lipoprotein ( ox-LDL) and inflammation induced by lipopolysaccharide ( LPS ) in RAW264.7 cells.Methods Foam cells were established by incubating the RAW264.7 cells with ox-LDL.The concentration of lipid droplets in the cells was observed by oil red staining, and the level of total cholesterol (TC) in cells was measured by enzyme method.The gene and protein expressions of scavenger receptors CD36 and SR-A1, ATP binding cassette transporters A1 and Gl ( ABCA1 and ABCGI) were detected by RT-qPCR and Western blot, respectively.The expressions of inter- leukin-6 (IL-6), interleukin-1 (3 (IL-ip), monocyte chemoattractant protein-1 (MCP-1 ) and tumor necrosis factor-a (TNF-a) were detected by ELISA and RT-qPCR.The protein expressions of mTOR and p-mTOR were detected by Western blot.Results Compared with model group, the high dose of Kudinoside D decreased the content of TC and down-regulated the gene and protein expression of SR-A induced by ox-LDL.Meanwhile Kudinoside D also decreased the levels of IL-ip and MCP-1 and down-regulated the protein expression of p-mTOR induced by LPS.Conclusions Kudinoside D may reduce the intracellular TC content by down-regulating the gene and protein expression of SR-A1.Kudinoside D may play an anti-inflammatory role through mTOR pathway.

Study on protective effect of total flavonoids from Rosa multiflora on HUVEC induced by ox-LDL / 中国中药杂志

The aim of this paper was to study the protective effect of total flavonoids from Rosa multiflora(TF-RM) on the injury of HUVEC induced by oxidized low density lipoprotein(ox-LDL). SPF male SD rats were randomly divided into blank group, simvastatin group(1.8 mg·kg~(-1)·d~(-1)) and TF-RM group(2.5 g·kg~(-1)·d~(-1)), with 10 rats in each group. They were intragastrically administered with drugs for 7 days, and then blood was collected from the abdominal aorta to prepare drug-containing serum. The HUVEC injury model was established through ox-LDL induction, and added with 15% simvastatin, 5% TF-RM, 10% TF-RM, 15% TF-RM drug-containing serum and blank serum, respectively. Reactive oxygen species(ROS) was determined by flow cytometry. Nitric oxide(NO) content was determined by nitrate reductase method. The contents of ET-1, P-selectin, E-selectin, ICAM-1, VCAM-1, IL-1β, IL-6 and TNF-α were determined by ELISA. The expression of Lox-1 protein was determined by Western blot. Compared with the blank group, ROS level in HUVEC and the contents of ET-1, P-selectin, E-selectin, ICAM-1, VCAM-1 and IL-1β in HUVEC were significantly increased(P<0.05), NO decreased significantly(P<0.01),Lox-1 protein expression increased significantly(P<0.05), and TNF-α and IL-6 showed an increasing trend. Compared with the model group, TF-RM significantly reduced ROS level in HUVEC and ET-1, P-selectin, E-selectin, ICAM-1, TNF-α, IL-1β content in supernatant(P<0.05), significantly increased NO content(P<0.01), and inhibited Lox-1 protein expression(P<0.05). VCAM-1, IL-6 contents showed a decreasing trend. Serum containing TF-RM acts on lectin-like oxidized low-density lipoprotein receptors, and exerts a protective effect on vascular endothelial cells by reducing cell oxidative damage, regulating vasoactive substances, and reducing adhesion molecules and inflammatory cascades.

Role of oxidized low density lipoprotein in the diagnosis of atherosclerotic cardiovascular disease / 中华检验医学杂志

As a critical factor of atherosclerosis (AS), oxidized low-density lipoprotein (oxLDL) plays a crucial role in damaging vascular endothelial cells, promoting monocyte adhesion, inducing formation of foam cells and thrombosis. Many scholars have found that oxLDL could be used as a circulating biomarker for atherosclerotic cardiovascular disease. In this manuscript, research progress on the mechanism of oxLDL in the initiation and development of atherosclerosis, as well as using oxLDL as a diagnostic biomarker of atherosclerosis related diseases were systemically reviewed.

Oxidized related substance of methionine in compound amino acid injection (18AA-Ⅱ) / 中国药科大学学报

@#TA method for the content determination of methionine sulfoxide and methionine sulfone in compound amino acid injection (18AA-II) was established in order to investigate their level in 155 batches of this product, and to explore the reason for the generation of these two impurities.The determination was performed on an Agilent Poroshell 120 EC-C18 column with mobile phases of sodium acetate/tetrahydrofuran solution (A) and sodium acetate solution -acetonitrile-methanol (B, 200∶400∶400) (gradient elution) at the flow rate of 0.5 mL/min.The excitation wavelength and the emission wavelength of the fluorescence detector were 233 nm and 441 nm, respectively.The column temperature was 40 °C, and the injection volume was 8 μL.The contents of methionine sulfoxide and methionine sulfone from 155 batches of compound amino acid injection (18AA-II) was determined using this method, and the residual oxygen content was detected by headspace gas analyzer.The results showed that the linear range of methionine sulfoxide and methionine sulfone were 0.128 1-10.250 0 μg/mL (r = 0.999 9) and 0.261 0-10.440 0 μg/mL (r = 0.999 8), respectively.The limits of quantitation were 0.13 μg/mL and 0.26 μg/mL, respectively; the limits of detection were 0.04 μg/mL and 0.09 μg/mL, respectively.RSDs of precision, stability and repetitive test were all lower than 1.3%.The recoveries ranged 98.00%-100.79% (RSD = 1.15%, n = 9) and 98.19%-102.31% (RSD = 1.33%, n = 9).The content level of oxidized related substances from different manufacturers showed significant difference, showing relevance with the residual oxygen content to some extent, yet no significant correlation with the added amount of antioxygen (sodium pyrosulfite).The method is validated to be useful for the content control of methionine sulfoxide and methionine sulfone in compound amino acid injection (18AA-II).It is quite necessary to include the determination of oxidized related substance into the quality specification.Manufacturers should strengthen the control of remaining oxygen in their products.

Oxidized low-density lipoprotein stimulates dendritic cells maturation via LOX-1-mediated MAPK/NF-κB pathway

Dendritic cells (DCs) play a crucial role as central orchestrators of immune system response in atherosclerosis initiation and progression. Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) is involved in the immune maturation of DCs, but the underlying mechanisms remain unclear. We isolated mouse bone marrow progenitors and stimulated them with granulocyte-macrophage colony-stimulating factor and interleukin (IL)-4 to induce immature DCs. We then treated DCs with oxidized low-density lipoprotein (oxLDL) to induce maturation. LOX-1 siRNA was used to investigate the modulation of LOX-1 on the development of DCs and the underlying signal pathways. CD11c-positive DCs were successfully derived from mouse bone marrow progenitors. OxLDL promoted the expressions of DCs maturation markers and pro-inflammatory cytokines. OxLDL also upregulated LOX-1 expression and activated MAPK/NF-κB pathways. LOX-1 siRNA could attenuate the expression of MAPK/NF-κB pathways and inflammatory cytokines. In conclusion, oxLDL induced the maturation of DCs via LOX-1-mediated MAPK/NF-κB pathway, which contributed to the initiation and progression of atherosclerosis.

Effect of Klotho on oxidized low density lipoprotein-induced endothelial cell senescence via activation of autophagy / 解放军医学杂志

Objective: To investigate the effect of Klotho on oxidized low density lipoprotein (ox-LDL)-induced human coronary artery endothelial cell (HCAEC) senescence via activation of autophagy. Methods: HCAECs were cultured in vitro, and divided into control group and ox-LDL group [treated with ox-LDL at different concentrations (0, 25, 50, 75, 100 μg/ml) or different durations (0, 24 h, 48 h, 72 h, 96 h) 2 h after pre-incubation with Klotho (400 pmol/L)]. Cell viability was tested by CCK-8, senescent cells were detected by SA-β-GAL staining, immunofluorescence was used to detect the intracellular expression of P53 and P16, and Western blotting was performed to quantitatively analyze the P53, P16, LC3 and P62 protein expression. HCAECs were pre-incubated separately with Klotho (400 pmol/L), rapamycin (5 μmol/L) or chloroquine (2 μmol/L) for 2 hours under normal culture condition, and then cultured under ox-LDL exposure (75 μg/ml) for 72 hours. Cell viability was tested by CCK-8, senescent cells were detected by SA-β-GAL staining, autophagic flux was assayed by adenovirus GFP-LC3, and Western blotting was performed to quantitatively analyze the P53, P16, LC3, and P62 protein expression. Results: The results of CCK-8 assay, SAKlotho β-GAL staining and Western blotting respectively showed that Klotho decreased ox-LDL-induced inhibition of HCAECs viability (P<0.05), reduced the proportion of senescent cells (P<0.05), and down-regulated the expression of aging-related proteins P53 and P16 (P<0.05). Western blotting revealed that ox-LDL decreased LC3-II/LC3-I ratio and increased P62 protein expression level in a time-dependent (P<0.05) or dose-dependent manner (P<0.05) to some extent. Furthermore, Klotho increased LC3-II/LC3-I ratio (P<0.01), decreased P62 protein expression level (P<0.01), and reduced the inhibition of autophagy by chloroquine under ox-LDL exposure (P<0.05). The results of CCK-8 assay, SA-β-GAL staining and Western blotting respectively indicated that the HCAECs viability (P<0.01), the proportion of senescent cells (P<0.01), and the protein expression levels of P53 (P<0.01) and P16 (P<0.01) were significantly alleviated in ox-LDL+Klotho group and ox-LDL+rapamycin group than those in ox-LDL group; while the HCAECs viability (P<0.01), the proportion of senescent cells (P<0.01), and the protein expression levels of P53 and P16 (P<0.05) were obviously worse in chloroquine+ox-LDL group than those in ox-LDL group. Conclusion: Klotho ameliorates ox- LDL-induced HCAEC senescence via activation of autophagy.

Preparation and performance evaluation of carboxymethyl chitosan/oxidized glucomannan/panax notoginseng compound sponge dressing for chronic wound / 中国组织工程研究

BACKGROUND: Previous studies have shown that carboxymethyl chitosan/oxidized glucomannan composite sponge can be used as an excellent substrate for drug-loaded chronic wound dressings. OBJECTIVE: To prepare carboxymethyl chitosan/oxidized glucomannan/Panax notoginseng composite sponge and evaluate its physical and chemical properties and biocompatibility. METHODS: Oxidized glucomannan was prepared by sodium periodate oxidation. Panax notoginseng saponins were extracted from Panax notoginseng powder. Carboxymethyl chitosan and oxidized glucomannan were first added as mixed raw materials, and then added separately to account for mixing system 2%, 6%, 10% of Panax notoginseng saponins. Freeze-drying method was used to prepare carboxymethyl chitosan/oxidized glucomannan/Panax notoginseng composite sponge. Scanning electron microscope was utilized to observe the microstructure of the composite sponge. Porosity, steam permeability, total saponin release rate of Panax notoginseng, cell compatibility, antibacterial properties and acute systemic toxicity were detected. RESULTS AND CONCLUSION: (1) Scanning electron microscope showed that there were many pores in the composite sponge that were full and evenly distributed. The total saponins of Panax notoginseng were stably and evenly attached to the inner walls and joints of the pores of the sponge. (2) As the proportion of total saponins of Panax notoginseng increased, the water absorption rate, porosity, and steam permeability gradually increased. (3) The vast majority of the total saponins of Panax notoginseng in the three kinds of composite sponges could be efficiently released in 13 hours in vitro. (4) Within 3 days after in vitro culture, the proliferation rate of fibroblasts was more than 95%. (5) Three kinds of compound sponges have an inhibitory effect on E. coli and Staphylococcus aureus, but do not have acute systemic toxicity. (6) The results show that carboxymethyl chitosan/oxidized glucomannan/Panax notoginseng composite sponge is expected to be an excellent medical chronic wound dressing.