基于网络药理学吴茱萸致肝毒性机制研究

目的筛选吴茱萸主要肝毒性成分,预测毒性成分作用靶点,探讨其多成分-多靶点-多通路的肝毒性作用机制。方法依据TCMSP数据库、PubChem数据库Pharmmapper服务器、UniprotKB数据库筛选吴茱萸的活性成分,并预测肝毒性作用靶点。借助Cytoscape软件构建吴茱萸毒性成分-作用靶点网络,通过KOBAS3.0数据库对靶点基因功能及代谢通路进行分析。结果网络分析结果表明吴茱萸中筛选得到14-甲酰基二氢吴茱萸次碱、芳樟醇、1-甲基-2-戊烷基-4(1H)喹诺酮、辛弗林、柠檬烯等147个潜在毒性成分,涉及靶点F2、PIM1、MMP13、MAOB等49个,经建立网络连接,细胞代谢、催化活性、刺激反应等通路可能与肝毒性作用相关。结论应用网络药理学的方法,发现吴茱萸中的多种潜在毒性成分可能通过多个靶点与细胞代谢、催化活性等通路相互作用,从而可能产生肝毒性,为后续进一步深入验证吴茱萸肝毒性作用机制研究提供新线索。     

苇茎汤合麻杏石甘汤加减联合半量激素治疗儿童毒热闭肺证难治性肺炎支原体肺炎

目的:观察苇茎汤合麻杏石甘汤加减联合半量激素治疗儿童毒热闭肺型难治性肺炎支原体肺炎的临床疗效。方法:120例患儿随机分为对照组和观察组,各60例。在基础治疗基础上,对照组给予连花清瘟颗粒+甲强尼龙(每次10 mg·kg-1,2次/日),观察组给予苇茎汤合麻杏石甘汤加减+甲强尼龙(每次10 mg·kg-1,1次/日),疗程均为14 d。观察两组治疗前后肺功能指标[最大通气量(MVV),呼气达峰时间(TPTEF),第1秒用力呼气容积(FEV1),呼气达峰容积(VPTEF)],血浆心肌酶谱[肌酸激酶(CK),肌酸激酶同工酶(CKMB),乳酸脱氢酶(LDH),胫丁酸脱氢酶(HBDH)],免疫功能[免疫球蛋白G(IgG),免疫球蛋白M(IgM),红细胞免疫复合物(RBC-ICR),红细胞C3b受体(RBC-C3bR)],炎性因子[肿瘤坏死因子-α(TNF-α),γ-干扰素(IFN-γ),白细胞介素-13(IL-13),白细胞介素-17A(IL-17A)],临床疗效和不良反应。结果:研究期间脱落4例。观察组总有效率96.6%(57/59),高于对照组的84.2%(48/57)(P<0.05)。与对照组治疗后比较,观察组MVV,TPTEF,FEV1,VPTEF,RBC-C3bR,IL-13升高(P<0.05);CK,CKMB,LDH,HBDH,IgG,IgM,RBC-ICR,TNF-α,IFN-γ和IL-17A降低(P<0.05)。观察组不良反应发生率低于对照组(P<0.05)。结论:苇茎汤合麻杏石甘汤加减联合半量激素可明显改善毒热闭肺型难治性肺炎支原体肺炎患儿的肺功能,心肌酶谱,免疫功能和炎性因子水平,不良反应发生率低。     

黄芪多糖对毒胡萝卜素诱导人结肠癌系HT29细胞内质网应激的影响

目的探讨黄芪多糖(Astragalus polysaccharides,AP)对毒胡萝卜素内酯(Thapsigargin,Tg)诱导人结肠癌系HT29细胞发生内质网应激(Endoplasmic Reticulum Stress,ERS)时内质网结构变化及相关分子GRP78和CHOP的影响。方法常规培养HT29细胞后,将细胞分为4组:①空白细胞组(Control组):细胞不做任何药物处理;②细胞模型组(Model组):采用1μmol/L Tg诱导HT29细胞建立ERS模型;③黄芪多糖低浓度组(AP-L组);④黄芪多糖高浓度组(AP-H组)。CCK8法检测黄芪多糖对HT29细胞活性,透射电镜观察内质网结构变化,Real-time PCR法检测ERS时GRP78、CHOP mRNA表达情况。结果黄芪多糖浓度分别为1、10μg/mL,且分别作用HT29细胞12、24、36、48 h时,细胞存活率随着浓度的增加而增加,说明对细胞无明显毒副作用。透射电镜观察Control组内质网结构呈网膜状结构,网膜腔不扩张;Model组内质网形态迥异,大小不一,呈空泡状改变,部分可见融合成簇现象;AP-L组内质网网膜腔扩张程度减轻,空泡体积减小和数量减少;AP-H组内质网形态基本恢复正常,呈网膜状结构,可见数量较少,形态较小的空泡状结构。Real-time PCR法检测结果:与Control组相比,Model组HT29细胞GRP78、CHOP mRNA表达明显增加(P<0.05);与Model组比较,AP-L组和AP-H组HT29细胞GRP78、CHOP mRNA表达均减少(P<0.05);与AP-L组比较,AP-H组HT29细胞GRP78、CHOP mRNA表达减少(P<0.05)。结论黄芪多糖能够抑制Tg诱导HT29细胞发生ERS,其机制可能与降低GRP78和CHOP的表达、减轻内质网应激有关。     

Poppers Maculopathy: Complete Restitution of Macular Changes in OCT after Drug Abstinence

Background: “Poppers” is a slang term for a group of alkyl nitrites that are used as recreational drugs. Their inhalative intoxication leads to muscle relaxation, analgesia, and euphoria. Maculopathy is a rare but serious side-effect. Patients/Methods: Clinical, imaging, and electrophysiological findings of seven patients with maculopathy after consumption of poppers were presented. Results: All seven patients were male with a median age of 35 years (range 28–45 years), the median duration of periodical poppers use until the onset of symptoms was 9.8 years (one day to 25 years). Five of seven patients were HIV-positive, one patient was negative, and the HIV-status of one patient was unknown. Median average of visual acuity at presentation was 20/30 in each eye. In all patients, optical coherence tomography (OCT) showed pathognomonic alterations of the outer foveal retina. One patient showed an almost complete restitution of the maculopathy six months after cessation of drug use and following the oral intake of Lutein. Imaging alterations returned to normal and visual acuity recovered from 20/50 and 20/30 (right and left eye, respectively) to 20/20 on both eyes. Follow up of two other cases showed no relevant functional decline or improvement. Discussion: Toxic maculopathy due to the consumption of poppers is an important differential diagnosis in acute visual loss without clinico-morphological correlate. Optical coherence tomography is the only reliable diagnostic tool in these cases. Complete recovery of visual function and macular morphology is rare, even after cessation of drug abuse. Oral lutein therapy may have a beneficial effect.     

Treatment of oral manifestations of toxic epidermal necrolysis with low‐level laser therapy in a pediatric patient

Drug‐induced reactions are complications associated with high mortality and significant morbidity. Stevens–Johnson Syndrome (SJS) and toxic epidermal necrolysis (TEN) are examples of these conditions, which are characterized by skin and mucous lesions. Here, we report a case of a 9‐year‐old girl who presented with blisters associated with an extensive vesicular rash and multiple ulcerations on the lips and oral cavity. A drug‐induced hypersensitivity reaction to antibiotics was suspected, and a diagnosis of TEN was made. The patient was managed with withdrawal of the suspected causative agent, and the oral lesions were treated with low‐level laser therapy (LLLT) and oral hygiene. This case highlights that TEN requires interdisciplinary intervention with dental assistance and follow‐up to improve symptoms, nutrition, systemic condition, and quality of life.     

Idiopathic toxic epidermal necrolysis in an adolescent

A 10‐year‐old girl, suspected 2 days prior to have streptococcal pharyngitis, presented with diffuse erythema, tense bullae, Nikolsky‐positive desquamation, as well as ulcerations of her oral and genital mucosa. She denied recent travel, sick contacts, or preceding and concurrent use of medications, including over‐the‐counter and herbal supplements. A comprehensive viral polymerase chain reaction (PCR) panel, Mycoplasma pneumoniae PCR and IgM, streptococcal molecular antigen test, urine culture, blood culture, and rheumatologic serologies were negative. Based on the patient's clinical presentation and biopsy results, she was diagnosed with idiopathic toxic epidermal necrolysis.     

Toxic tau: structural origins of tau aggregation in Alzheimer's disease

Alzheimer’s disease is characterized by the extracellular accumulation of the amyloidβin the form of amyloid plaques and the intracellular deposition of the microtubule-associated protein tau in the form of neurofibrillary tangles.Most of the Alzheimer’s drugs targeting amyloidβhave been failed in clinical trials.Particularly,tau pathology connects greatly in the pathogenesis of Alzheimer’s disease.Tau protein enhances the stabilization of microtubules that leads to the appropriate function of the neuron.Changes in the quantity or the conformation of tau protein could affect its function as a microtubules stabilizer and some of the processes wherein it is involved.The molecular mechanisms leading to the accumulation of tau are principally signified by numerous posttranslational modifications that change its conformation and structural state.Therefore,aberrant phosphorylation,as well as truncation of tau protein,has come into focus as significant mechanisms that make tau protein in a pathological entity.Furthermore,the shape-shifting nature of tau advocates to comprehend the progression of Alzheimer’s disease precisely.In this review,we emphasize the recent studies about the toxic and shape-shifting nature of tau in the pathogenesis of Alzheimer’s disease.     

Challenging infections in pregnancy

Maternal sepsis is “a life-threatening condition defined as organ dysfunction resulting from infection during pregnancy, childbirth, post-abortion, or postpartum period.” (World Health Organisation, 2017). Serious infection during, or immediately after, pregnancy may go initially unrecognized in an otherwise young and healthy group, who nevertheless do have a compromized immune system. Secondly, whilst malaise, flushes, nausea, vomiting and abdominal pain are common in pregnancy, each can herald sepsis with rapid demise for mother and baby. The MBRRACE-UK report in 2017¹ found an overall sepsis-related maternal mortality rate of 0.56 per 100,000 maternities with a mortality rate from genital tract sepsis of 0.28 per 100,000 maternities. This review will focus on the major causes, recognition, differentiation and microbiological management of sepsis in pregnancy, using two detailed cases to illustrate.