Effect of sodium nitroprusside on the microrheological properties of red blood cells in different media

Red blood cell(RBC)aggregation as well as their deformation significantly affects blood microrheology.These processes depend on various factors,one of which is concentration of the nitric oxide,one of the main signaling molecule in the bloodstream.The purpose of this study was to investigate the effect of nitric oxide on the microrheological properties of red blood cells(RBCs)in RBC samples of various media after the addition of nitric oxide donor sodium nitroprusside in vitro.Microrheological properties were measured using laser aggregometer and ektacytometer based on diffuse light scattering and diffraction of laser light on a suspension of RBCs,respectively.The study found that heparin-stabilized blood showed increased RBC aggregation and deformation with sodium nitroprusside concentrations of 100,and 200M,while EDTA-stabilized blood showed slightly decreased aggregation and unchanged deformation.With washed RBCs in dextran solution,the addition of sodium nitroprusside(in the concentrations of 100,and 200M)resulted in decreased aggregation and increased deformation.These-ndings aid in our understanding of nitric oxide's effect on RBC microrheological properties.

Cerebral arterial blood flow,attention,and executive and cognitive functions in depressed patients after acute hypertensive cerebral hemorrhage

BACKGROUND Intracerebral hemorrhage mainly occurs in middle-aged and elderly patients with hypertension,and surgery is currently the main treatment for hypertensive cerebral hemorrhage,but the bleeding caused by surgery will cause damage to the patient's nerve cells,resulting in cognitive and motor dysfunction,resulting in a decline in the patient's quality of life.AIM To investigate associations between cerebral arterial blood flow and executive and cognitive functions in depressed patients after acute hypertensive cerebral hemorrhage.METHODS Eighty-nine patients with depression after acute hypertensive cerebral hemorrhage who were admitted to our hospital between January 2019 and July 2021 were selected as the observation group,while 100 patients without depression who had acute hypertensive cerebral hemorrhage were selected as the control group.The attention span of the patients was assessed using the Paddle Pin Test while executive function was assessed using the Wisconsin Card Sorting Test(WCST)and cognitive function was assessed using the Montreal Cognitive Assessment Scale(MoCA).The Hamilton Depression Rating Scale(HAMD-24)was used to evaluate the severity of depression of involved patients.Cerebral arterial blood flow was measured in both groups.RESULTS The MoCA score,net scores I,II,III,IV,and the total net score of the scratch test in the observation group were significantly lower than those in the control group(P<0.05).Concurrently,the total number of responses,number of incorrect responses,number of persistent errors,and number of completed responses of the first classification in the WCST test were significantly higher in the observation group than those in the control group(P<0.05).Blood flow in the basilar artery,left middle cerebral artery,right middle cerebral artery,left anterior cerebral artery,and right anterior cerebral artery was significantly lower in the observation group than in the control group(P<0.05).The basilar artery,left middle cerebral artery,right middle cerebral artery,left anterior cerebral artery,and right anterior cerebral artery were positively correlated with the net and total net scores of each part of the Paddle Pin test and the MoCA score(P<0.05),and negatively correlated with each part of the WCST test(P<0.05).In the observation group,the post-treatment improvement was more prominent in the Paddle Pin test,WCST test,HAMD-24 score,and MoCA score compared with those in the pre-treatment period(P<0.05).Blood flow in the basilar artery,left middle cerebral artery,right middle cerebral artery,left anterior cerebral artery,and right anterior cerebral artery significantly improved in the observation group after treatment(P<0.05).CONCLUSION Impaired attention,and executive and cognitive functions are correlated with cerebral artery blood flow in patients with depression after acute hypertensive cerebral hemorrhage and warrant further study.

Molecular Characterization of RHD in Rh-Negative Blood Donors in Congo Brazzaville

Background: The D antigen is the most important and immunogenic antigen of the Rh blood group;its correct screening prevents any risk of alloimmunization in the RHD negative recipient. The D negative phenotype is characterized by the absence of the D antigen (RH1) on the surface of the erythrocyte. Three main mechanisms can generate this absence: total or partial deletion of the RHD gene, insertion of base pairs within the said gene and gene conversion. The objective of this study was to report the first data on RHD genotyping in RHD negative congolese blood donors. Materials and Methods: Blood samples came from regular RHD-negative blood donors selected from the blood transfusion stations in Brazzaville and Pointe-Noire. They were analyzed individually by conventional PCR, targeting exons 4, 5, 7 and 10 of the RHD gene. Results: Fifty-nine regular RHD negative blood donors were selected for this study. The immuno-hematological profile was determined individually, and the dccee phenotype was the most frequent (n = 52;88.1%). The search for the weak D antigen was negative for all donors. Exons 4, 5, 7 and 10 of the RHD gene were amplified in the following respective proportions: 89.8%, 81.4%, 6.8% and 42.4%. Moreover, (1) donor was found to carry all four specific exons sought. Conclusion: Conventional PCR amplification allowed to study the presence of specific exons of the targeted D gene. At least one exon was detected in the entire study population. These results suggest that the RHD gene is indeed present in the donors studied and that the deletion cannot be considered as the main mechanism causing the RH-1 (D negative) phenotype in this sample.

Blood biomarkers of Alzheimer’s disease:important considerations for use in clinical practice

Introduction:Fluid and positron emission tomography(PET)biomarkers that enable the detection of the hallmark proteins of Alzheimer’s disease(AD)(amyloid and tau)have revolutionized our approach to the diagnosis of AD.The evolution of AD diagnostic criteria to include biological characterization(Alzheimer’s Association Working Group,2023)provides an appropriate framework to reduce levels of clinico-pathologic mismatch and improve in-vivo diagnostic accuracy.As the therapeutic landscape for neurodegenerative disease evolves,it is increasingly incumbent on clinicians to provide timely,and pathologically precise diagnoses for patients.However,the expensive and invasive nature of these tests limits their scalability.

Beyond wrecking a wall:revisiting the concept of blood–brain barrier breakdown in ischemic stroke

The blood–brain barrier constitutes a dynamic and interactive boundary separating the central nervous system and the peripheral circulation.It tightly modulates the ion transport and nutrient influx,while restricting the entry of harmful factors,and selectively limiting the migration of immune cells,thereby maintaining brain homeostasis.Despite the well-established association between blood–brain barrier disruption and most neurodegenerative/neuroinflammatory diseases,much remains unknown about the factors influencing its physiology and the mechanisms underlying its breakdown.Moreover,the role of blood–brain barrier breakdown in the translational failure underlying therapies for brain disorders is just starting to be understood.This review aims to revisit this concept of“blood–brain barrier breakdown,”delving into the most controversial aspects,prevalent challenges,and knowledge gaps concerning the lack of blood–brain barrier integrity.By moving beyond the oversimplistic dichotomy of an“open”/“bad”or a“closed”/“good”barrier,our objective is to provide a more comprehensive insight into blood–brain barrier dynamics,to identify novel targets and/or therapeutic approaches aimed at mitigating blood–brain barrier dysfunction.Furthermore,in this review,we advocate for considering the diverse time-and location-dependent alterations in the blood–brain barrier,which go beyond tight-junction disruption or brain endothelial cell breakdown,illustrated through the dynamics of ischemic stroke as a case study.Through this exploration,we seek to underscore the complexity of blood–brain barrier dysfunction and its implications for the pathogenesis and therapy of brain diseases.

Refractory lipoatrophy treated with autologous whole blood injection:A case report

BACKGROUND Intramuscular corticosteroid injection may cause adverse effects such as dermal and/or subcutaneous atrophy,alopecia,hypopigmentation,and hyperpigmentation.Although cutaneous atrophy can spontaneously resolve,several treatment options have been suggested for this condition.CASE SUMMARY In this paper,we report a case of corticosteroid injection induced lipoatrophy treated with autologous whole blood(AWB)injection,as the condition had been unresponsive to fractional laser therapy.A 29-year-old female patient visited the dermatology clinic complaining of skin depression on her right buttock area,which had appeared six months earlier.There had been only subtle improvement at the margins after fractional CO_(2) laser treatment;therefore,after obtaining informed consent from the patient,AWB treatment was initiated.One month after the first AWB injection,the size and depth of the lesion had noticeably improved,and a slight improvement was also observed in discoloration.CONCLUSION Close observation is the initial treatment of choice for steroid induced skin atrophy;however,for patients in need of immediate cosmetic improvement,AWB injection may be a safe and cost-effective alternative.

Pretreatment red blood cell distribution width as a predictive marker for postoperative complications after laparoscopic pancreatoduodenectomy

BACKGROUND Red blood cell distribution width(RDW)is associated with the development and progression of various diseases.AIM To explore the association between pretreatment RDW and short-term outcomes after laparoscopic pancreatoduodenectomy(LPD).METHODS A total of 804 consecutive patients who underwent LPD at our hospital between March 2017 and November 2021 were retrospectively analyzed.Correlations between pretreatment RDW and clinicopathological characteristics and short-term outcomes were investigated.RESULTS Patients with higher pretreatment RDW were older,had higher Eastern Cooperative Oncology Group scores and were associated with poorer short-term outcomes than those with normal RDW.High pretreatment RDW was an independent risk factor for postoperative complications(POCs)(hazard ratio=2.973,95%confidence interval:2.032-4.350,P<0.001)and severe POCs of grade IIIa or higher(hazard ratio=3.138,95%confidence interval:2.042-4.824,P<0.001)based on the Clavien-Dino classification system.Subgroup analysis showed that high pretreatment RDW was an independent risk factor for Clavien-Dino classi-fication grade IIIb or higher POCs,a comprehensive complication index score≥26.2,severe postoperative pancreatic fistula,severe bile leakage and severe hemorrhage.High pretreatment RDW was positively associated with the neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio and was negatively associated with albumin and the prognostic nutritional index.CONCLUSION Pretreatment RDW was a special parameter for patients who underwent LPD.It was associated with malnutrition,severe inflammatory status and poorer short-term outcomes.RDW could be a surrogate marker for nutritional and inflammatory status in identifying patients who were at high risk of developing POCs after LPD.

The pivotal role of microglia in injury and the prognosis of subarachnoid hemorrhage

Subarachnoid hemorrhage leads to a series of pathological changes,including vascular spasm,cellular apoptosis,blood–brain barrier damage,cerebral edema,and white matter injury.Microglia,which are the key immune cells in the central nervous system,maintain homeostasis in the neural environment,support neurons,mediate apoptosis,participate in immune regulation,and have neuroprotective effects.Increasing evidence has shown that microglia play a pivotal role in the pathogenesis of subarachnoid hemorrhage and affect the process of injury and the prognosis of subarachnoid hemorrhage.Moreover,microglia play certain neuroprotective roles in the recovery phase of subarachnoid hemorrhage.Several approaches aimed at modulating microglia function are believed to attenuate subarachnoid hemorrhage injury.This provides new targets and ideas for the treatment of subarachnoid hemorrhage.However,an in-depth and comprehensive summary of the role of microglia after subarachnoid hemorrhage is still lacking.This review describes the activation of microglia after subarachnoid hemorrhage and their roles in the pathological processes of vasospasm,neuroinflammation,neuronal apoptosis,blood–brain barrier disruption,cerebral edema,and cerebral white matter lesions.It also discusses the neuroprotective roles of microglia during recovery from subarachnoid hemorrhage and therapeutic advances aimed at modulating microglial function after subarachnoid hemorrhage.Currently,microglia in subarachnoid hemorrhage are targeted with TLR inhibitors,nuclear factor-κB and STAT3 pathway inhibitors,glycine/tyrosine kinases,NLRP3 signaling pathway inhibitors,Gasdermin D inhibitors,vincristine receptorαreceptor agonists,ferroptosis inhibitors,genetic modification techniques,stem cell therapies,and traditional Chinese medicine.However,most of these are still being evaluated at the laboratory stage.More clinical studies and data on subarachnoid hemorrhage are required to improve the treatment of subarachnoid hemorrhage.

Blood diagnostic and prognostic biomarkers in amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis is a devastating neurodegenerative disease for which the current treatment approaches remain severely limited.The principal pathological alterations of the disease include the selective degeneration of motor neurons in the brain,brainstem,and spinal cord,as well as abnormal protein deposition in the cytoplasm of neurons and glial cells.The biological markers under extensive scrutiny are predominantly located in the cerebrospinal fluid,blood,and even urine.Among these biomarke rs,neurofilament proteins and glial fibrillary acidic protein most accurately reflect the pathologic changes in the central nervous system,while creatinine and creatine kinase mainly indicate pathological alterations in the peripheral nerves and muscles.Neurofilament light chain levels serve as an indicator of neuronal axonal injury that remain stable throughout disease progression and are a promising diagnostic and prognostic biomarker with high specificity and sensitivity.However,there are challenges in using neurofilament light chain to diffe rentiate amyotrophic lateral sclerosis from other central nervous system diseases with axonal injury.Glial fibrillary acidic protein predominantly reflects the degree of neuronal demyelination and is linked to non-motor symptoms of amyotrophic lateral sclerosis such as cognitive impairment,oxygen saturation,and the glomerular filtration rate.TAR DNA-binding protein 43,a pathological protein associated with amyotrophic lateral sclerosis,is emerging as a promising biomarker,particularly with advancements in exosome-related research.Evidence is currently lacking for the value of creatinine and creatine kinase as diagnostic markers;however,they show potential in predicting disease prognosis.Despite the vigorous progress made in the identification of amyotrophic lateral sclerosis biomarkers in recent years,the quest for definitive diagnostic and prognostic biomarke rs remains a formidable challenge.This review summarizes the latest research achievements concerning blood biomarkers in amyotrophic lateral sclerosis that can provide a more direct basis for the differential diagnosis and prognostic assessment of the disease beyond a reliance on clinical manifestations and electromyography findings.

Peripheral blood RNA biomarkers can predict lesion severity in degenerative cervical myelopathy

Degenerative cervical myelopathy is a common cause of spinal cord injury,with longer symptom duration and higher myelopathy severity indicating a worse prognosis.While numerous studies have investigated serological biomarkers for acute spinal cord injury,few studies have explored such biomarkers for diagnosing degenerative cervical myelopathy.This study involved 30 patients with degenerative cervical myelopathy(51.3±7.3 years old,12 women and 18 men),seven healthy controls(25.7±1.7 years old,one woman and six men),and nine patients with cervical spondylotic radiculopathy(51.9±8.6 years old,three women and six men).Analysis of blood samples from the three groups showed clear differences in transcriptomic characteristics.Enrichment analysis identified 128 differentially expressed genes that were enriched in patients with neurological disabilities.Using least absolute shrinkage and selection operator analysis,we constructed a five-gene model(TBCD,TPM2,PNKD,EIF4G2,and AP5Z1)to diagnose degenerative cervical myelopathy with an accuracy of 93.5%.One-gene models(TCAP and SDHA)identified mild and severe degenerative cervical myelopathy with accuracies of 83.3%and 76.7%,respectively.Signatures of two immune cell types(memory B cells and memory-activated CD4^(+)T cells)predicted levels of lesions in degenerative cervical myelopathy with 80%accuracy.Our results suggest that peripheral blood RNA biomarkers could be used to predict lesion severity in degenerative cervical myelopathy.

Autologous cord blood vs individualized supplements in autistic spectrum disorder:CORDUS study results

BACKGROUND Cellular therapies have started an important new therapeutic direction in autistic spectrum disorder(ASD),and the ample diversity of ASD pathophysiology and the different types of cell therapies prompt an equally ample effort to employ clinical studies for studying the ASD causes and cell therapies.Stem cells have yielded so far mixed results in clinical trials,and at patient level the results varied from impressive to no improvement.In this context we have administered autologous cord blood(ACB)and a non-placebo,material intervention repre-sented by an individualized combination of supplements(ICS)to ASD children.METHODS CORDUS clinical study is a crossover study in which both oral ICS and intravenous ACB were sequentially administered to 56 children;ACB was infused as an inpatient procedure.Treatment efficacy was evaluated pre-treatment and post-treatment at 6 months by an independent psychotherapist with Autism Treatment Evaluation Checklist,Quantitative Checklist for Autism in Toddlers and a 16-item comparative table score,after interviewing the children’s parents and therapists.Before and after each intervention participants had a set of blood tests including inflammatory,metabolic and oxidative markers,and the neuronal specific enolase.RESULTS No serious adverse reactions were noted during and after cord blood or supplement administration.ACB improved evaluation scores in 78%of children with age 3–7-years(n=28),but was much less effective in kids older than 8 years or with body weight of more than 35 kg(n=28;only 11%of children improved scores).ICS yielded better results than ACB in 5 cases out of 28,while in 23 kids ACB brought more improvement than ICS(P<0.05);high initial levels of inflammation and ferritin were associated with no improvement.Ample individual differences were noted in children's progress,and statistically significant improvements were seen after ACB on areas such as verbalization and social interaction,but not on irritability or aggressive behavior.CONCLUSION ACB has superior efficacy to ICS in ASD;high inflammation,ferritin,age and body weight predict less improvement;more clinical studies are needed for studying ACB efficacy in ASD.

郑州地区RhD变异型献血者分子生物学分析

目的研究郑州地区RhD变异型献血者血清学特征及基因突变机制。方法选择2023年1月—2023年12月送至本实验室的1619名RhD阴性献血者为研究对象,应用试管法和微柱凝胶间接抗球蛋白试验方法进行RhD阴性确认试验及RhCE表型检测。采用RHD基因扩增和Sanger测序检测RhD变异型标本基因型。结果RhD阴性确认试验共检出RhD变异型69例,比例为4.26%(69/1619)。RhCE表型分别为ccEe、Ccee、CcEe、CCee。包含17种基因型,15种D变异型表型。RHD^(*)weak partial 15等位基因最多(33例),频率为47.83%(33/69),主要表型为ccEe;其次是RHD^(*)DVI.3等位基因20例,频率为28.99%(20/69),主要表型为Ccee。RHD^(*)weak partial 15/RHD^(*)01EL.01杂合子3例,频率为4.35%(3/69),皆为CcEe表型。其他罕见基因型共13例,频率为18.84%(13/69)。抗筛阳性3例,比例为4.35%(3/69)。女性献血者2名,皆有孕产史,经抗体鉴定为抗-D;男性献血者1名,为抗-M。结论郑州地区RhD变异型献血者中RHD^(*)weak partial 15基因型最常见,其次为RHD^(*)DVI.3基因型。对保障安全供血,指导临床精准输血具有重要作用。

2例罕见RhD变异型RHD*DEL37的分子生物学分析

Rh血型系统是输血医学中重要的常规检测血型系统,因RhD血型不合引起的溶血性输血反应及新生儿溶血病一直以来倍受临床重视。本研究报道了2例罕见的RHD基因变异型RHD*DEL37个体的血清学和基因特征,这2例个体的血液样本经血清学方法(试管法和微柱凝胶法)鉴定为RhD阴性。采用聚合酶链反应-序列特异性引物(polymerase chain reaction-sequence specific prime,PCR-SSP)对样本进行RHD基因分型和合子型分析,基因分型结果为RHD基因阳性,并排除了常见的几种RHD基因变异体的可能。RHD基因合子型检测阳性,证明其中一条RHD等位基因1~10外显子全部缺失。进一步对样本RHD基因1~10外显子基因进行Sanger法测序,测序结果显示在另一条等位基因第8内含子上的第1154-31号碱基发生了T>C突变,国际输血协会(International Society of Blood Transfusion,ISBT)将该突变等位基因命名为RHD*DEL37,表型为RhD放散型(D-elute,Del)。本研究中,2例血清学初筛RhD阴性的样本通过分子生物学检测,其基因型为RHD*DEL37/RHD-(RHD*01N.01)。由于这2例个体无血缘关系,提示我国可能存在携带该基因突变的人群。本研究提示分子生物学方法可辅助鉴别血清学初筛为阴性的RhD变异体样本,联用分子生物学方法和血清学方法在准确鉴定血型、保障患者输血安全方面有重要意义。

微量法筛血在Rh血型系统相容性输血中的应用研究

目的研究快速筛选患者Rh血型系统C、c、E和e意外抗体对应抗原阴性血液的方法以及该方法在相容性输血中的价值。方法文章以产生意外抗-e的O型患者为研究对象,使用微孔板稀释献血者红细胞,制备2%~5%红细胞悬液,用微量法检测标本红细胞Rh血型抗原,用标准法确定目标血液导管Rh血型抗原,比较两种方法的差异性。结果使用微量法检测的献血者标本Rh血型抗原结果与标准法确认结果100%相符,临床无溶血性输血反应发生。结论在不影响细胞凝集和结果观察的前提下,微量法可以节约近70%的试剂、耗材成本,且该方法简便易行,为临床产生Rh血型系统意外抗体患者的精准输血治疗赢取宝贵时间,适合基层血站和输血科开展应用。

血清抗体、血红蛋白、胆红素、心肌酶及肝酶联合对新生儿Rh溶血病的诊断效果

目的研究血清抗体、血红蛋白、胆红素、心肌酶及肝酶联合对新生儿Rh溶血病的诊断效果。方法选择2021年7月至2022年11月于赣州市人民医院分娩的53例新生儿Rh溶血病患儿,按照疾病严重程度分为重症组20例和轻症组33例,检测并比较血清抗体、血红蛋白、胆红素、心肌酶及肝酶水平,分析其诊断价值。结果重症组血红蛋白低于轻症组,胆红素、肌酸激酶、丙氨酸氨基转移酶高于对照组(P<0.05);两组血清抗体比较,差异无统计学意义(P>0.05);经logistic多因素分析结果显示,血清血红蛋白(β=-0.136,OR=0.873,95%CI:0.814~0.936)是新生儿Rh溶血病的保护因素(P<0.05);胆红素(β=0.031,OR=1.032,95%CI:1.012~1.052)、肌酸激酶(β=0.093,OR=1.098,95%CI:1.039~1.160)及丙氨酸氨基转移酶(β=0.120,OR=1.128,95%CI:1.042~1.221)是新生儿Rh溶血病的危险因素(P<0.05);绘制ROC曲线图,结果显示,血清血红蛋白、胆红素、心肌酶及肝酶联合检测在新生儿Rh溶血病诊断中的AUC分别为0.938、0.817、0.815、0.929、0.977,均有一定诊断价值。结论血清血红蛋白、胆红素、心肌酶及肝酶联合检测在新生儿Rh溶血病诊断中有一定应用价值。

中国人输血产生RhCE同种抗体的风险和预防策略

目的探索一种评估输血产生RhCE同种抗体风险的新途径,并制定选择RhCE相容供者的策略。方法根据兰德施泰纳法则和群体遗传学原理,确定在随机输血中供者与受者RhCE抗原错配的组合,根据中国人Rh血型分布大数据资料,计算错配组合的概率以及找到相容供者的机会。结果分析文献报告的458542例中国人RhD、C、c、E和e抗原分型资料,结果表明在只采用RhD同型输血的策略中,RhCE抗原错配占全部输血的25.16%,其中Rh表型DCCee、DccEE、DCcee和DccEe错配分别占比14.97%、5.01%、2.21%和2.26%,表型Dccee、DCCEE、DCCEe和DCcEE错配合计占比0.71%。Rh表型DCcEe个体可以接受任何Rh表型供者的血液。结论中国人Rh血型以高频率DCe单倍型为特征,Rh表型DCCee个体是随机输血后产生RhCE同种抗体的高风险群体。RhC、c、E和e抗原分型对寻找Rh抗原匹配供者有重要意义。使用常见RhCE表型相容供者的输血,可以预防大约90%的受者产生RhCE同种抗体。

RH精炼钢包智能顶升模型及精度的研究

智能化RH精炼技术已成为钢铁生产行业的研究热点,钢包智能顶升技术是实现RH高效、稳定生产的关键。基于RH精炼过程的钢包顶升原理建立了钢包智能顶升模型,并分析了在线测距仪测量精度的影响因素。研究结果表明:阻尼系数为1.5 Ns/m,钢包车经过在线测距仪时运行速度为10 m/min,钢包中心经过在线测距仪正下方的-1000 mm至1000 mm,在线测距仪数值与净空计算模型的精准度较高,钢包智能顶升模型计算的自动顶升高度与实际顶升误差<5%,可用于RH精炼工艺的钢包智能顶升过程。

人参皂苷Rh2通过mTOR/ROS信号通路抑制卵巢颗粒细胞衰老

目的探讨人参及其主要活性成分人参皂苷Rh2抗胰岛素抵抗导致的卵巢颗粒细胞衰老的作用及机制。方法采用网络药理学、分子对接和细胞热位移分析法(Cellular thermal shift assay,CETSA)检测人参抗卵巢储备减少(Diminished ovarian reserve,DOR)和衰老的核心分子及其潜在的下游信号通路。用胰岛素(0.5μg/ml,72 h)处理人卵巢颗粒细胞(KGN)作为卵巢衰老的体外模型,将KGN细胞分为3组:对照组、胰岛素组(0.5μg/ml,72 h)以及胰岛素(0.5μg/ml,72 h)+人参皂苷Rh2组(2μmol/L,24 h)。β-半乳糖苷酶染色、CCK-8、活性氧检测试剂盒、免疫蛋白印迹以及qRT-PCR检测KGN细胞活性以及衰老相关因子(p53、p21)的表达水平。结果网络药理学筛选出人参有效成分、DOR和衰老核心度最高的10个共同靶点,即TNF、ESR1、MAPK3、PPARG、STAT3、HSP90AA1、NR3C1、mTOR、AR以及NOS3。人参中主要的活性成分为人参皂苷Rh2。与胰岛素组相比,人参皂苷Rh2(2μmol/L,24 h)能够降低KGN细胞中衰老细胞占比及活性氧(ROS)活性;同时,人参皂苷Rh2能够抑制KGN细胞中p53以及p21的表达升高。分子对接结果显示,mTOR是人参皂苷Rh2抗DOR以及衰老的关键靶点。过表达mTOR能够逆转人参皂苷Rh2抑制KGN细胞的活性降低和细胞衰老,逆转人参皂苷Rh2抑制KGN细胞ROS水平下降。结论人参皂苷Rh2可能通过调控mTOR/ROS抑制胰岛素抵抗导致的卵巢颗粒细胞衰老,从而发挥抵抗DOR的作用。

人参皂苷Rh1通过激活Nrf2/HO-1信号通路对糖尿病小鼠肾脏损伤的改善作用

目的:探讨人参皂苷Rh1对糖尿病(DM)小鼠肾损伤的保护作用,并阐明其作用机制。方法:应用高脂高糖饲养佐以腹腔注射链脲佐菌素(STZ)法制备糖尿病肾脏疾病(DKD)模型。将48只C57/BL6成模小鼠随机分为模型组、核因子红细胞2相关因子2(Nrf2)抑制剂ML385组(ML385组)(30 mg·kg^(-1)ML385)、人参皂苷Rh1组(G-Rh1组)(30 mg·kg^(-1)人参皂苷Rh1)和G-Rh1+ML385组(30 mg·kg^(-1)人参皂苷Rh1+30 mg·kg^(-1)ML385),每组12只,另外12只C57/BL6小鼠作为对照组。作用8周后,全自动分析仪检测各组小鼠血清中空腹血糖(FBG)、尿素氮(BUN)和血肌酐(Scr)水平及尿液中24 h尿蛋白(24 h UP)水平,并计算肾脏指数。试剂盒检测各组小鼠肾组织中超氧化物歧化酶(SOD)和乳酸脱氢酶(LDH)活性及丙二醛(MDA)水平,Western blotting法检测各组小鼠肾组织中Nrf2和血红素加氧酶1(HO-1)蛋白表达水平。结果:与对照组比较,模型组、ML385组和G-Rh1+ML385组小鼠血清中FBG水平和肾脏指数均明显升高(P<0.01),G-Rh1组小鼠血清中FBG水平明显升高(P<0.01);与模型组比较,ML385组小鼠肾脏指数明显升高(P<0.05),G-Rh1组小鼠FBG水平和肾脏指数均明显降低(P<0.05或P<0.01);与G-Rh1组比较,G-Rh1+ML385组小鼠FBG水平和肾脏指数均明显升高(P<0.01)。与对照组比较,模型组、ML385组、G-Rh1组和G-Rh1+ML385组小鼠血清中BUN和Scr水平及尿液中24 h UP水平均明显升高(P<0.01);与模型组比较,ML385组小鼠血清中BUN水平及尿液中24 h UP水平均明显升高(P<0.05),G-Rh1组小鼠血清中BUN和Scr水平及尿液中24 h UP水平均明显降低(P<0.01);与G-Rh1组比较,G-Rh1+ML385组小鼠血清中BUN和Scr水平及尿液中24 h UP水平均明显升高(P<0.01)。与对照组比较,模型组、ML385组、G-Rh1组和G-Rh1+ML385组小鼠肾组织中SOD活性均明显降低(P<0.01),MDA水平和LDH活性均明显升高(P<0.01);与模型组比较,ML385组小鼠肾组织中SOD活性明显降低(P<0.05),MDA水平明显升高(P<0.05),G-Rh1组小鼠肾组织中SOD活性明显升高(P<0.01),MDA水平和LDH活性均明显降低(P<0.01);与G-Rh1组比较,G-Rh1+ML385组小鼠肾组织中SOD活性明显降低(P<0.01),MDA水平和LDH活性均明显升高(P<0.01)。与对照组比较,模型组、ML385组、G-Rh1组和G-Rh1+ML385组小鼠肾组织中Nrf2和HO-1蛋白表达水平均明显降低(P<0.05或P<0.01);与模型组比较,ML385组和G-Rh1+ML385组小鼠肾组织中Nrf2和HO-1蛋白表达水平均明显降低(P<0.05),G-Rh1组小鼠肾组织中Nrf2和HO-1蛋白表达水平均明显升高(P<0.01);与G-Rh1组比较,G-Rh1+ML385组小鼠肾组织中Nrf2和HO-1蛋白表达水平均明显降低(P<0.01)。结论:人参皂苷Rh1可降低氧化应激,改善肾功能,对DM小鼠肾脏损伤具有保护作用,其作用机制可能与激活Nrf2/HO-1信号通路有关。

RH精炼炉用耐材技术研究进展

简述了RH精炼炉的分类和冶炼工艺,总结了RH精炼炉用耐火材料的主要种类及其损毁机理,详细论述了RH精炼炉用高档镁铬砖、镁尖晶石砖、低碳MgO-C砖、尖晶石-C砖、含ZrO_(2)/Y_(2)O_(3)的MgO砖、MgAlON结合MgO质耐火材料,以及不定形耐材技术的研究新进展概况,并指出我国RH精炼炉用耐材技术取得的显著进步,但与国外新技术相比仍存在一定差距,未来仍有较大的发展空间。