1例重度急性胰腺炎患者抗感染治疗的药学监护

摘 要临床药师参与1例重度急性胰腺炎患者的药物治疗,结合患者病史、临床症状及实验室指标等,根据病原学检测结果,借助万古霉素血药浓度监测进行抗感染方案调整,并协助医生对患者制定个体化用药方案。经治疗后,患者病情得到基本控制,且未出现相关药品不良反应。提示临床药师在参与患者治疗过程中,可结合患者特殊的生理病理状态、药物浓度监测及临床反应等,协助临床医师优化药物治疗方案,提高患者用药的有效性和安全性。     

Childhood polybrominated diphenyl ether (PBDE) exposure and executive function in children in the HOME Study

Prenatal exposure to polybrominated diphenyl ethers (PBDEs) have been reported to impair executive function in children, but little is known whether childhood PBDE exposures play a role. Using the Health Outcomes and Measures of the Environment (HOME) Study, a prospective birth cohort in the greater Cincinnati area, we investigated the association between repeated measures of PBDEs during childhood and executive function at 8 years in 208 children and whether effect modification by child sex was present. We used child serum collected at 1, 2, 3, 5, and 8 years to measure PBDEs. The Behavior Rating Inventory of Executive Function was completed by parents to assess executive function at 8 years. We used multiple informant models to examine childhood PBDEs during several exposure windows. Null associations were observed between early childhood PBDEs and executive function. However, we observed significant adverse associations between a 10-fold increase in concurrent concentrations of BDE-28 (β = 4.6, 95% CI 0.5, 8.7) and BDE-153 (β = 4.8, 95% CI 0.8, 8.8) with behavioral regulation. In addition, PBDEs at 8 years were significantly associated with poorer emotional and impulse control. No associations were noted between childhood PBDEs and metacognition or global executive function. However, child sex significantly modified the associations, with significantly poorer executive function among males with higher concurrent BDE-153, and null associations in females. Our study findings suggest that concurrent PBDE exposures during childhood may be associated with poorer executive function, specifically behavior regulation. Males may also be more sensitive to adverse associations of concurrent PBDEs on executive function.     

黄芪注射液对小儿呼吸道感染红细胞免疫指标的影响

目的：观察黄芪注射液对小儿反复呼吸道感染红细胞免疫指标的影响。方法：对体检的健康儿童６０例（对照组）进行红细胞Ｃ３ｂ受体花环试验、淋巴细胞绝对值测定和植物血凝素（ＰＨＡ）皮肤试验。６０例呼吸道反复感染患儿（治疗组）除常规治疗外，并给予黄芪注射液静滴，于治疗前后分别进行上述检验。结果：治疗组治疗后总有效率达９８．３％。治疗后免疫功能３项指标均明显优于治疗前（Ｐ均＜０．０１）；治疗组治疗后免疫功能３项指标与健康对照组比较均无显著性差异（Ｐ均＞０．０５）。结论：在西药抗生素及抗病毒治疗基础上，加用黄芪注射液具有增强免疫功能的作用，是治疗小儿反复呼吸道感染及免疫功能低下的一种新途径。     

Combining NSAM and CPC concentrations to determine airborne nanoparticle count median diameter: Application to various laboratory and workplace aerosols

Because nanomaterials have been increasingly developed and used in many technology and industry sectors over the last 20 years, an increasing number of workers is likely to be exposed to airborne nanoparticles. In addition, the question of the nanomaterial characteristics that should be assessed in epidemiological studies remains open. Thus, assessing occupational exposure to airborne nanoparticles will not only rely on mass concentration and chemical composition. Rather, key parameters, such as particle size, have to be included in measurement strategies.

We previously proposed a methodology to estimate the Count Median Diameter (CMD) of an aerosol based on the simultaneous size-integrated measurement of two particle concentrations, lung-deposited surface area, and number, thanks to field-portable, commercially available aerosol instruments (Nanoparticle Surface Area Monitor/Condensation Particle Counter combination).

In addition to previous work, this study investigates the case of various polydisperse metal oxides, organic oil, and salt particles with CMDs ranging from 16–410 nm. Once corrected, the CMDs derived from the NSAM/CPC agree within ±20% with regard to the reference electrical mobility equivalent diameter, regardless of aerosol composition, morphology, or geometric standard deviation (GSD).

Furthermore, the field-applicability of the method was tested through 6 sets of experimental data stemming from workplace measurement campaigns where different materials were produced and handled (TiO₂, SiO₂, Ag, Multi-Walled Carbon Nanotubes—MWCNT), covering a range of CMDs between 40 and 190 nm. All situations considered, the approach based on the combination of a NSAM and a CPC leads to a satisfying estimation of particle CMD, within ±20% compared to reference CMD.     

注射用磷酸特地唑胺细菌内毒素检查

目的：注射用磷酸特地唑胺用于特定的敏感细菌引起的成人急性细菌性皮肤和皮肤结构感染,于2014年6月20日,被美国FDA批准磷酸特地唑胺上市,临床研究也进入了临床II期,用于严重革兰氏阳性菌感染的治疗。该药尚未在中国上市。未被中国药典2015年版收录,没有与之相关的质量标准,所以需要尽快制定药品的检验标准,已完善医药市场对药物的质量要求与监管。方法：参照中国药典2015年版二部,拟定的质量标准并对细菌内毒素检查的方法学进行了验证。结果：拟定本品的细菌内毒素限值为1.5EU/mg,当采用灵敏度为0.5EU/ml的鲎试剂,样品浓度为含磷酸特地唑胺4mg/ml时,对内毒素与鲎试剂的反应无干扰。结论：当采用两个鲎试剂生产厂家的试剂对样品进行干扰试验,灵敏度为0.5EU/ml,样品浓度为含磷酸特地唑胺4mg/ml时,对内毒素与鲎试剂的反应无干扰。此限值为可靠限值。此浓度为本品的最大无干扰浓度。     

免疫抑制剂血药浓度与肾移植术后腹泻的关联性分析

目的 探讨免疫抑制剂霉酚酸酯（MMF）、他克莫司（FK506）血药浓度与肾移植术后腹泻之间的关系。方法 选取2015年8月至2017年8月在安徽医科大学第一附属医院行肾移植手术的146例受者,根据术后是否发生腹泻分为两组,未发生腹泻的患者为非腹泻组（83例）、发生腹泻且大于1次者为腹泻组（63例）,测定受者的霉酚酸谷浓度（MPA-C₀）和FK506谷浓度（FK506-C₀）,记录术后出现的腹泻情况,运用统计软件分析MPA-C₀和FK506-C₀与腹泻间的关系。结果 腹泻组与非腹泻组之间MPA-C₀差异无统计学意义（P>0.05）,FK506-C₀差异有统计学意（P<0.001）;ROC曲线分析显示,FK506-C₀仅在术后1个月差异有统计学意义（曲线下面积0.607,P<0.05）,FK506 C₀<11.15 ng/mL是术后1个月发生腹泻的截断值,敏感度51.90%,特异性63.60%;MPA-C₀与FK506-C₀对腹泻发生不存在交互作用（P>0.05）。结论 MPA-C₀与腹泻的发生没有关联性,而较高的FK506-C₀易导致肾移植术后腹泻,其中术后1个月FK506-C₀ <11.15 ng/mL是发生腹泻的的最佳截断值。     

A comprehensive review on Brigatinib – A wonder drug for targeted cancer therapy in non-small cell lung cancer

The mortality rate in patients suffering from non-small cell lung cancer (NSCLC) is quite high. This type of cancer mainly occurs due to rearrangements in the anaplastic lymphoma kinase (ALK) gene which leads to form an oncogene of fused gene NPM-ALK. Brigatinib is recently approved by FDA in April 2017 as a potent tyrosine kinase inhibitor (TKI) for the NSCLC therapy. In the present scenario, it is no less than a wonder drug because it is indicated for the treatment of advanced stages of metastatic ALK positive NSCLC, a fatal disease to overcome the resistance of various other ALK inhibitors such as crizotinib, ceritinib and alectinib. In addition to ALK, it is also active against multiple types of kinases such as ROS1, Insulin like growth factor-1Receptor and EGFR. It can be synthesized by using N-[2-methoxy-4-[4-(dimethylamino) piperidin-1-yl] aniline] guanidine and 2,4,5-trichloropyrimidine respectively in two different ways. Its structure consists of mainly dimethylphosphine oxide group which is responsible for its pharmacological activity. It is active against various cell lines such as HCC78, H2228, H23, H358, H838, U937, HepG2 and Karpas- 299. Results of ALTA (ALK in Lung Cancer Trial of AP26113) phase ½ trial shows that 90?mg of brigatinib for 7?days and then 180?mg for next days is effective in the treatment of NSCLC. Brigatinib has been shown to have favorable risk benefit profile and is a safer drug than the available cytotoxic chemotherapeutic agents. In comparison to other FDA approved drugs for the same condition, it causes fewer minor adverse reactions which can be easily managed either by changing the dose or by providing good supportive care. This article is intended to provide readers with an overview of chemistry, pharmacokinetic, pharmacodynamic and safety profile of brigatinib, which addresses an unmet medical need.     

Indocyanine green loaded hyaluronan-derived nanoparticles for fluorescence-enhanced surgical imaging of pancreatic cancer

Pancreatic ductal adenocarcinoma is highly lethal and surgical resection is the only potential curative treatment for the disease. In this study, hyaluronic acid derived nanoparticles with physico-chemically entrapped indocyanine green, termed NanoICG, were utilized for intraoperative near infrared fluorescence detection of pancreatic cancer. NanoICG was not cytotoxic to healthy pancreatic epithelial cells and did not induce chemotaxis or phagocytosis, it accumulated significantly within the pancreas in an orthotopic pancreatic ductal adenocarcinoma model, and demonstrated contrast-enhancement for pancreatic lesions relative to non-diseased portions of the pancreas. Fluorescence microscopy showed higher fluorescence intensity in pancreatic lesions and splenic metastases due to NanoICG compared to ICG alone. The in vivo safety profile of NanoICG, including, biochemical, hematological, and pathological analysis of NanoICG-treated healthy mice, indicates negligible toxicity. These results suggest that NanoICG is a promising contrast agent for intraoperative detection of pancreatic tumors.     

Multimodal imaging for a theranostic approach in a murine model of B-cell lymphoma with engineered nanoparticles

Nanoparticles (NPs) are a promising tool for in vivo multimodality imaging and theranostic applications. Hyaluronic acid (HA)-based NPs have numerous active groups that make them ideal as tumor-targeted carriers. The B-lymphoma neoplastic cells express on their surfaces a clone-specific immunoglobulin receptor (Ig-BCR). The peptide A20-36 (pA20-36) selectively binds to the Ig-BCR of A20 lymphoma cells. In this work, we demonstrated the ability of core-shell chitosan-HA-NPs decorated with pA20-36 to specifically target A20 cells and reduce the tumor burden in a murine xenograft model. We monitored tumor growth using high-frequency ultrasonography and demonstrated targeting specificity and kinetics of the NPs via in vivo fluorescent reflectance imaging. This result was also confirmed by ex vivo magnetic resonance imaging and confocal microscopy. In conclusion, we demonstrated the ability of NPs loaded with fluorescent and paramagnetic tracers to act as multimodal imaging contrast agents and hence as a non-toxic, highly specific theranostic system.     

不同收入分层视角下居民卫生服务利用的公平性分析*

目的分析宁夏银川市居民卫生服务利用及其公平性,为促进不同收入水平下居民的卫生服务利用公平性提供政策建议。方法采用分层随机抽样的方法,入户问卷调查18岁及以上的银川市居民。应用频数与构成比的方法描述被调查居民的一般情况。运用两周患病率、慢性病患病率、两周就诊率和住院率分析居民卫生服务利用情况,运用集中指数CI反映不同收入阶层居民卫生服务利用的公平性分布。结果本次研究调查显示,被调查整体居民的两周患病率为14.27%,集中指数为-0.011 5,偏向低收入人群。慢性病患病率为13.08%,集中指数为0.040 4,偏向高收入人群。居民两周就诊率为12.49%,集中指数为-0.006 1,绝对值近似为0,较公平。居民住院率为9.71%,集中指数为-0.015 0,倾向于发生在低收入人群。结论不同收入水平居民的卫生服务利用公平性仍需改善,建议政府及相关部门加强健康教育宣传力度,大力发展经济,提高低收入人群的经济能力,出台相应的控费政策。