BACKGROUND:Allergic rhinitis (AR) is a prevalent chronic inflammatory nasal disorder with suboptimal current therapies. Glycyrrhizic acid (GA), a bioactive triterpenoid from Glycyrrhiza uralensis, exerts well-documented antiinflammatory effects, and preliminary evidence indicates its efficacy in alleviating airway inflammation in AR models. However, two critical knowledge gaps remain unaddressed: whether GA directly binds to core proteins of the toll-like receptor 4 (TLR4)/nuclear factor-kappa B (NF-κB)/IL-1β inflammatory pathway, and whether this binding mediates GA's therapeutic effects in AR have not been systematically verified by integrated computational and in vivo experiments. METHODS:An ovalbumin (OVA)-induced AR rat model was established. GA was administered intranasally for seven consecutive days. Behavioral observations, histopathological examination, and serum cytokine detection were performed to evaluate AR-related symptoms and immune imbalance. Molecular docking was employed to assess the binding affinity between GA and four key proteins in the TLR4 pathway (TLR4, myeloid differentiation primary response 88 [MyD88], NF-κB, and IL-1β). About 100 ns molecular dynamics (MD) simulations were further conducted to validate the stability of the GA-protein complexes. Immunohistochemistry and RT-qPCR were used to verify the expression of pathway-related proteins and cytokines in nasal mucosal tissues. RESULTS:GA significantly reduced sneezing, rhinorrhea, and nasal mucosal pathological damage in AR rats. It restored the T helper 1 (Th1)/Th2 immune balance by suppressing Th2 cytokines (IL-4 and IL-13) and enhancing Th1 cytokines (interferon-gamma [IFN-γ] and IL-2). Molecular docking results showed that GA bound strongly to all four target proteins, with the highest affinity for IL-1β (-9.3 kcal/mol) and TLR4 (-7.6 kcal/mol). MD simulations confirmed the stable conformational dynamics of the GA-IL-1β and GA-TLR4 complexes. In vivo experiments further demonstrated that GA significantly downregulated the expression of TLR4, MyD88, NF-κB, and IL-1β in nasal mucosa and reduced the levels of downstream proinflammatory cytokines (TNF-α and IL-6). CONCLUSIONS:GA alleviates AR symptoms by directly binding to core proteins of the TLR4/NF-κB/IL-1β pathway, inhibiting pathway activation, restoring Th1/Th2 immune balance, and suppressing inflammatory responses. This study provides structural and functional evidence supporting GA as a promising targeted therapeutic candidate for AR.

Background: Multidrug resistance (MDR) of cancer cells is a major obstacle to efficient cancer chemotherapy. Combination therapy is expected to enhance the anticancer effect and reverse MDR. Numerous patents involve different kinds of nanoparticles for the co-delivery of multiple chemotherapeutics, but the FDA has approved none. Objective: In this study, oxymatrine (OMT) and glycyrrhizin (GL) were co-loaded into phytosomes as the core of nanocarriers, and the shell was cross-linked with chitosan (CS) and hyaluronic acid (HA) with the capability for the controlled, sequential release and the targeted drug uptake Methods: Phospholipid complexes of OMT and GL (OGPs) were prepared by a solvent evaporation technique and could self-assemble in an aqueous solution to form phytosomes. CS and HA were sequentially coated on the surface of OGPs via electrostatic interactions to obtain CS coated OGPs (CS-OGPs) and HA modified CS-OGPs (HA-CS-OGPs), respectively. The particle size and zeta potential were measured to optimize the formulations. In vitro cytotoxicity and cellular uptake experiments on HepG2 cells were performed to evaluate the anticancer activity. Results: OGPs were obtained with nano-size around 100 nm, and CS and HA coating on phytosomes could change the particle size and surface potential. The drug loading of OMT and GL showed that the nanocarriers could maintain a fixed ratio of 1:1. The in vitro release experiments indicated the release of OMT and GL was pH-dependent and sequential: the release of OMT from CS-OGPs and HA-CS-OGPs was significantly increased at pH 5.0 compared to the release at pH 7.4, while GL exhibited sustained released from CS-OGPs and HA-CS-OGPs at pH 5.0. Furthermore, in vitro cytotoxicity and cellular uptake experiments on HepG2 cells demonstrated that the co-delivery system based on phytosomes had significant synergistic anti-tumor activities, and the effects were enhanced by CS and HA modification. Conclusion: The delivery of OMT and GL via HA-CS-OGPs might be a promising treatment to reverse MDR in cancer therapy.

Bacterial infection is the main cause of infectious diseases in children. Antibacterials play an important role in anti infection treatment of children. At present, the treatment of antimicrobial drugs in children is facing a severe situation of bacterial resistance. In January 2020, a children′s specialized hospital carried out the practice of precise management of antibiotics in combination with key performance indicators. Through the multi sectoral linkage of management and technology, eight key performance indicators and assessment methods were set up from three levels of antibiotic use, bacterial resistance and hospital infection, to standardize the clinical application of antibiotics and continue to promote the rational use of antibiotics. This practice had improved the performance indicators of antibacterial management. Among them, the use intensity of antibacterial drugs for inpatients decreased from 40.07 DDD in 2019 to 29.00 DDD in 2021, the use rate of antibacterial drugs for inpatients decreased from 81.32% to 64.40%, the percentage of antibacterial drug expenses in total drug expenses decreased from 35.41% to 26.82%, the use proportion of non restricted antibacterial drugs in antibacterial drugs increased from 71.30% to 82.21%, and the drug resistance rate of Salmonella to β-Lactam/enzyme inhibitors decreased from 4.84% to 0.03%, and the incidence of hospital infection decreased from 1.16% to 0.96%. The precise management of antibiotics in combination with key performance indicators improved the level of rational use of antibiotics, effectively curbed bacterial resistance, achieved phased results, so as to provide a reference for the scientific management of antibiotics in children′s hospitals.

目的 分析儿童专科医院药物不良事件报告现状,实施药物不良事件标准化管理,提高医疗服务质量.方法 运用5M1E方法回顾分析2020年通过自愿呈报与全面触发工具法得到的药物不良事件数量差异原因,提出标准化管理对策,对比分析2020年和2021年数据,查看实施效果.结果 与2020年实施管理之前相比,干预组(2021年)自愿呈报得到的药物不良事件上报率、可预防率及F级事件上报数量显著增加(p﹤0.05),两种方法检测结果的一致率从75.69％提高至96.65％,差异具有统计学意义(p﹤0.01).结论 实施药物不良事件标准化上报管理,针对高发、典型的ADE进行有效地追踪、整改、评价,实现了ADE的闭环管理,发挥了ADE上报系统在提高合理用药水平、保障儿童安全用药方面的作用.

Cysteinyl leukotrienes (CysLTs) modulate central nervous system inflammatory responses via their receptors, CysLT1R and CysLT2R. It has been demonstrated that CysLTR participates in the infection process of Streptococcus pneumoniae (SP)-induced meningitis. In the present study, the effects and possible underlying mechanisms of CysLTR antagonists (pranlukast and HAMI 3379) on SP meningitis were further determined. SP meningitis was induced by intracerebroventricular injection of serotype III SP in Sprague-Dawley rats which were administrated intraperitoneally with 0.1 mg/kg antagonists. The clinical disease status of rats was evaluated by body weight and behavioral changes with neurological scoring. Survival neuron density, activated microglial and astrocytes were assessed by Nissl staining and immunohistochemical staining. The expression levels of inflammatory cytokines and NLRP3 inflammasome were detected by reverse transcription-quantitative PCR and western blotting, respectively. Pranlukast and HAMI 3379 treatment markedly alleviated the clinical disease status, which was manifested by improving body weight loss and neurological deficit. Furthermore, pranlukast and HAMI 3379 treatment ameliorated neuronal injury and inhibited microgliosis and astrogliosis. In addition, significant downregulation of inflammatory cytokines and NLRP3 expression was observed in pranlukast and HAMI 3379-treated rats. These in vivo findings indicated the neuroprotective effects of CysLTR antagonists against experimental SP-induced meningitis, and the mechanism of anti-inflammatory effects may partly be by inhibiting NLRP3 inflammasome overactivation.

目的 规范美罗培南临床使用,促进合理用药.方法 通过根因分析法,研究美罗培南不合理使用的原因,根据原因设计使用前、中、后的各项管理措施,实施全流程管理及专档管理.结果 2018年4月—2021年3月,美罗培南使用前病原微生物送检率维持在98％以上,住院患儿的药物使用率总体呈线性下降趋势(y=-0.815x+3.0033,R2=0.8744).第二阶段与第一阶段相比,变化不明显(χ2=3.235,p=0.072),第三阶段较第二阶段明显下降(χ2=124.687,p<0.001).美罗培南的AUD、使用金额等也呈下降趋势.耐碳青霉烯类耐药菌的检出率均为0.结论 基于RCA及全程监管可促进美罗培南的合理规范使用.

The objective of the present research was to formulate diammonium glycyrrhizinate (DG) into phytosomes (DG-P) to induce nasal immune responses and enhance absorption. Plackett- Burman design was used for process optimization, incorporating specific formulation and process variables to obtain the optimal parameters. Fourier transform infrared spectroscopy (FTIR), X-ray power diffraction (P-XRD), and transmission electron microscopy (TEM) were used for characterization. The adjuvant activity of the DG-P was evaluated by using bone marrow dendritic cells. In vitro nasal mucosal permeation and in situ nasal perfusion were also investigated to evaluate nasal absorption. The DG phytosomes were in the size range of 20~30 nm and zeta-potential range of −30~−40 mV. DG-P demonstrated 4.2-fold increased solubility in n-octanol. Coculturing bone marrow dendritic cells with DG-P led to enhanced dendritic cell maturation. Apparent permeability coefficient of the phytosomal formulation was almost four times higher than that of free DG determined by ex vivo permeation studies on excised porcine mucosa. In situ nasal perfusion studies in rats demonstrated that the nasal absorption of DG-P was significantly higher than that of free DG. Conclusively, the results confirmed that DG-P have potential for use as an adjuvant for nasal vaccine.

目的 分析儿科中成药使用及合理性,优化儿童中成药合理用药审核规则.方法 分析合理用药审核系统对儿童中成药处方点评结果,有针对性地改进儿童用药审核规则.结果 2019、2020和2021三年的第一季度中成药合理使用点评结果中,中成药不合理处方修改率由20.67％逐渐提高到43.93％、55.43％,系统审核处方合格率分别达到98.83％、99.06％和99.60％,系统审核处方合格率逐步提高.结论 分析、改进儿童中成药审核规则可进一步提高儿科中成药使用合理性,计算机人工智能合理用药审核软件有助于提高儿童中成药合理用药水平.

目的 探讨在儿童医院备用药品管理中运用医疗失效模式与效应分析(health care failure mode and effect analysis,HFMEA)和根原因分析(root cause analysis,RCA)的可行性.方法 根据追踪回溯法,使用HFMEA方法分析儿童医院备用药品的常规管理,罗列儿童医院备用药品使用管理中可能产生的失效因素,并用RCA法对其失效因素进行统计分析,找到影响医院备用药安全的主要因素,采取相应方法改进后取得一定效果.结果 HFMEA和RCA联合应用后,儿童医院由备用药品产生的不良事件发生率显著降低;影响备用药品安全管理的失效因数RPN值由182分下降到28分,对比各科发生备用药管理不合理情况应用前后具有统计学意义(p<0.05).结论 联合应用HFMEA和RCA法于儿童医院备用药品管理中,可有效阻止由备用药品导致的不良事件的发生,提高医院备用药品管理水平.

目的 探讨运用HFMEA联合SHEL模式降低儿童静脉药物配置中心(PIVAS)差错风险的有效性.方法 收集2018年1-12月期间某儿童医院PIVAS的差错记录,通过HFMEA联合SHEL模式对PIVAS环节每个可能导致用药错误的潜在风险进行风险优先(RPN)评分并进行原因分析及对策拟定、实施,从而降低风险.结果 2018年1-12月期间PIVAS共发生差错96例,以内部差错(不含发药环节差错)为主,占95.83％.导致用药错误发生的潜在失效模式共10项,实施干预前后RPN值为137和21,下降率为84.67％.结论 HFMEA联合SHEL模式可全面分析用药错误发生原因并制定相应对策,将差错管理前置化,有效降低PIVAS用药错误发生风险,保障儿童静脉用药安全.

目的 探讨医疗失效模式与效应分析(HFMEA)应用于儿童门诊静脉用药配置中心(PIVAS)输液安全管理的效果.方法 根据HFMEA方法,确立主题,成立门诊PIVAS输液安全管理团队,绘制工作流程,评估影响门诊输液失效的可能因素、原因及造成的影响,有针对性地制定改进措施,并追踪效果.结果 在应用HFMEA模式对门诊静脉用药配置各个环节加强管理后,医疗失效模式与效应分析的风险值(RPN)从56下降到32,RPN总分值与改善前相比下降了42.86％,输液失效的内部差错发生率下降了29.03％.结论 失效模式与效应分析作为一种风险管理工具,可以有效预防差错,降低门诊输液的失效率,提高儿童用药安全.

目的 开发药品语音二维码标签,应用于儿童用药指导,保障儿童安全用药.方法 首先通过ChsVoice(文字转语音)软件将每种药品的安全用药指导内容(文字形式)转换为语音文件,并利用二维码管理系统及云存储技术依次生成药品语音二维码,进行解码稳定性测试后打印为药品语音标签,并采用多指标评价体系对试用前后的各项指标进行评价.结果 药品语音二维码标签可通过安卓6.0系统和iOS9.0系统解码,最长字段不超过5.6MB,图片分辨率不低于80*95像素,图片大小不低于10KB.使用前后药品平均调配时间、药品正确使用理解率、二次咨询率、患者用药错误发生率、药品(普通VS语音)标签满意率、用药错误上报率均有显著性差异(p<0.01).结论 药品语音二维码标签将儿童安全用药指导的关键信息通过语音形式传递给家长,生动易懂,接受度高,实现全程化远程用药指导.

运用SWOT分析法,对儿科临床药师开展全程药学服务具有的优势、劣势及所面临的机遇与威胁进行系统分析,寻求合理的发展策略,探讨儿科临床药师开展全程药学服务的发展策略.儿科临床药师可利用优势及机遇,克服劣势及威胁,提高开展全程药学服务的质量,使药物应用更加安全、有效.

目的 探讨EV-71感染的普通型手足口病(HFMD)进展为危重型的影响因素,建立危重型HFMD的早期预警模型.方法 选择2016年杭州市某儿童医院收治的65例确诊为EV-71感染的手足口病患儿为研究对象,其中普通型30例,危重型35例.比较两组患儿的一般情况、现病史和实验室检查指标,采用单因素分析筛选风险因素,Logistic回归分析独立危险因素.建立早期预警模型,并采用受试者工作曲线(ROC)评价.结果 EV-71感染的普通型HFMD与危重病例在口腔疱疹、发热天数、最高体温、高热天数、发病至初诊时间、发病至入院时间、血糖、血清IgG水平存在明显差异(P＜0.05),Logistic模型显示血糖、最高体温、高热天数、发病至初诊时间和口腔疱疹是危重型手足口病的独立危险因素(P＜0.05).预测模型ROC曲线下面积(AUC)为0.915,模型的敏感度为89.2％,特异度为90.5％,总体准确率为89.7％.结论 密切观察EV-71感染的普通型HFMD患儿的血糖、最高体温、高热天数、发病至初诊时间和口腔疱疹,能够对危重症倾向进行早期预警.

脑膜脓毒黄杆菌(Chryseobacterium meningosepticum,CM)是一种少见的革兰染色阴性需氧杆菌、非条件致病菌,广泛存在于水、土壤甚至食物中,对新生儿和免疫低下的患者有很高的致病性,可引起早产儿败血症和脑膜炎,对多种抗菌药物耐药,致使患者病情较难控制,因而寻求有效安全的抗菌药物成为其治疗的关键.杭州市儿童医院近期收治了一例CM感染引起的新生儿败血症合并化脓性脑膜炎患儿,本文将结合文献就该患儿的抗感染治疗进行分析.

目的 临床药师通过对重症监护病房(Intensive Care Unit,ICU)患者抗菌药物的监测,评价抗菌药物的不良反应发生情况.方法 临床药师与临床医生共同参与ICU患者的抗感染治疗并进行药学监护,对易发生不良反应的抗菌药物进行重点监测.结果 抗菌药物不良反应表现形式多样,特定抗菌药物的特殊不良反应也会发生.在停用可疑药物后,这些不良反应均能得到控制,并基本恢复原有水平.结论 临床药师应关注ICU患者抗感染治疗中所用抗菌药物的不良反应,促进临床安全用药.

Streptococcus pneumoniae meningitis is an infection of the central nervous system associated with high mortality rates and serious neurologic sequelae in children. The principal reason for the severity of S. pneumoniae meningitis is widespread ignorance of the pathogenesis of the disease. This study aimed at exploring whether cysteinyl leukotriene receptor (CysLTR) participates in the inflammatory response and elucidates the pathologic process of S. pneumoniae meningitis. Bacterial meningitis disease models were constructed by intracisternal inoculation of rats with serotype III Streptococcus pneumoniae while control models were inoculated with the same volume of normal saline. Rats were sacrificed at different time points (1 d, 2 d, and 5 d) following the administration of Streptococcus pneumoniae. Results from the body-weight, Loeffler neurologic deficit score, and cerebrospinal fluid culture confirmed that a successful pneumococcal meningitis rat model was established. Pathologic changes in brain tissues mainly consisted of inflammation in the meninges and subarachnoid space and significant neuronal injury in the cerebral cortex and hippocampus (P < 0.05). Immunohistochemical analysis revealed that microglial activation and astrocyte proliferation were associated with the development of bacterial meningitis. The expression levels of CysLTR and inflammatory factor tumor necrosis factor-α (TNF-α) were examined by quantitative real-time polymerase chain reaction (qRT-PCR) and western blot analysis. The results of this study indicate that CysLTR expression was markedly elevated in the 5 d infection group (P < 0.05), which was consistent with time-dependent release of TNF-α. The findings of this study indicate that CysLTR participates in the pneumococcal meningitis infection process by mediating neuronal injury and glial cell proliferation. Cysteinyl leukotriene receptors could, therefore, be novel targets to mitigate the progression of pneumococcal meningitis.

目的 分析儿科中药物的不合理应用情况,探讨医院信息系统(hospital information system,HIS)与合理用药规则器的联用在儿童用药合理性中的作用.方法 通过逸曜合理用药系统对处方进行自动点评,发现药品的使用在用法用量、给药途径中存在不合理现象;然后利用HIS系统对常用药品的用法用量、给药途径进行预设;同时针对儿童用药的特殊性,在合理用药系统中进行儿童专用规则的设计.结果 通过HIS预设,用法用量、给药途径的不合理率分别从改进前的7.16％和0.57％下降到5.04％和0.19％.儿童专用规则器设定后,用法用量和给药途径错误比例呈逐年下降趋势,分别从2014年的3.44％和0.29％下降为2016年的1.01％和0.02％,四级和五级警示比例也分别从2014年的2.83％和0.35％下降为2016年的1.07％和0.11％,从而有效提高了处方合格率.结论 HIS的预设对医师开具处方的合理性具有明显作用,儿童专属规则器的设定可进一步提高用药的合理性.儿童用药资源的整合和人工智能的开发将有助于提高儿童的合理用药水平.

The purpose of this study was to develop and evaluate a transdermal delivery system for RIS using hydrogels. First, the effects of different concentrations of hydroxypropyl methylcellulose and Carbomer 934 (CBR) on RIS permeation were investigated in porcine skin. The optimized formulation was chosen as the base gel to screen for penetration enhancers. The pharmacokinetics of the optimized RIS formulation was then studied in vitro in rabbits. A formulation with 0.5% CBR showed the highest RIS permeation and was selected as the base gel. RIS permeation was further increased by incorporation of Azone, lauryl alcohol, or menthol, and the enhancing effects of the three were dose-dependent. When each enhancer combined with propylene glycol (PG) a synergistic effect was found. A combination of 6% menthol and 6% PG exhibited highest RIS in vitro penetration rate and showed a high efficiency in vivo, with a relative bioavailability of 131.53% compared with intragastric administration. These findings showed that 1% RIS in 0.5% CBR, containing a combination of 6% menthol and 6% PG, can deliver doses of RIS that are therapeutically relevant for treating patients with schizophrenia.

目的:探讨苦参碱口腔生物黏附凝胶在体外和人体口腔中的释放行为,并对其稳定性做初步考察.方法:采用Franz扩散池进行体外释放实验,4名健康志愿者进行口腔释放实验.HPLC测定扩散池中的苦参碱浓度和凝胶中的残留药物浓度.通过测定苦参碱含量、pH值、体外黏附性能评价凝胶的初步稳定性.结果:苦参碱口腔生物黏附凝胶的体外释放速率大于口腔释放,两者分别符合Korsmeyer-Pep-pas和Higuchi模型.稳定性实验结果显示苦参碱口腔生物黏附凝胶在强光、高湿和30℃加速条件下未发生明显变化,高温对苦参碱凝胶的药物浓度和体外黏附时间有影响.结论:苦参碱生物黏附凝胶可长时间口腔释放药物,并具有较好的理化稳定性.