我院310例抗菌药物不良反应相关影响因素分析

目的探讨我院抗菌药物不良反应（ADR）发生规律及特点,为临床用药安全提供参考。方法对我院2012年上报的310例抗菌药物ADR报告进行回顾性研究,登记患者性别、年龄、原患疾病,药品名称、给药途径,ADR名称、级别、转归。结果ADR集中发生在40～50岁年龄段,女性比男性比例高;新的、严重的ADR分别占总数的1．29％和6．45％;静脉滴注引起的ADR175例,占总数的56．45％,口服给药引起的ADR112例,占总数的36．13％;左氧氟沙星及阿奇霉素ADR发生比例高;ADR临床表现分布广泛,以皮肤及附件损害和消化系统损害为主。β-内酰胺类是引起严重ADR的主要抗菌药物。结论抗菌药物引起ADR的原因较为复杂,应加强监测,促进临床合理用药,保障患者用药安全。     

抗菌药物致不良反应547例分析

目的:探讨我院抗菌药物致不良反应(ADR)发生的相关影响因素,为临床用药安全提供参考。方法:对我院2011-2012年上报的抗菌药物致ADR 547例进行回顾性研究,统计、分析患者性别、年龄、ADR分级、ADR转归、ADR涉及药品、给药途径、ADR累及器官或系统及临床表现等。结果:ADR发生集中在41⁵0岁年龄段,女性比男性发生ADR的比例高;新的、严重的ADR分别占总数的0.73%、5.12%;其中,静脉滴注367例(占67.09%),口服给药153例(占27.97%);左氧氟沙星引发ADR比例最高(占23.40%);ADR临床表现以皮肤及其附件损害(占34.90%)和消化系统损害(占27.84%)为主。β-内酰胺类是引起严重ADR的主要抗菌药物。结论:抗菌药物致ADR影响因素较为复杂,医务工作者应加强对抗菌药物应用监测,促进临床合理用药,保障患者用药安全。     

某二甲医院 2010—2012 年抗菌药物不良反应报告回顾性分析

目的了解该院抗菌药物不良反应发生现状和特点以及影响因素,为保证抗菌药物的安全使用提供参考。方法 2010—2012年某院上报的抗菌药物不良反应报告237份,按患者性别、年龄、药物种类、名称、给药途径、药品不良反应（ADR）的性质、转归及临床表现、报告人员职业进行统计和分析。结果 237份ADR报告中,男性发生比例高于女性;41~50岁年龄段为ADR发生的主要人群,但老人及儿童发生的比例也较高;ADR以一般反应为主,严重的和新的ADR分别占总例数的3.80%和1.26%;静脉滴注为引发ADR为主要的给药途径,占总例数81.01%;ADR主要发生在用药后31~60 min;抗菌药物以喹诺酮类为主,占总例数29.12%,其次为大环内酯类（28.27%）和头孢菌素类（26.16%）,其中阿奇霉素为57例,占总例数24.05%,其次为左氧氟沙星（56例,23.63%）;药物不良反应主要表现为皮肤及附件损害（102例,43.04%）;护师ADR报告率68.35%。结论深入开展对抗菌药物不良反应的监测,加强对抗菌药物合理使用的认识,减少抗菌药物不良反应的发生。     

我院347例抗菌药物致不良反应分析

目的:了解我院抗菌药物致药品不良反应(ADR)发生的原因及特点。方法:对我院2005～2009年收集到的347例抗菌药物致ADR报告进行回顾性统计、分析。结果:我院347份ADR报告中共涉及9类抗菌药物,头孢菌素类及喹诺酮类引发的ADR最多,分别占36.60%(127例)、22.77%(79例)。其中,左氧氟沙星和头孢曲松所占比例最大,分别占14.70%、12.39%;ADR累及的器官或系统以皮肤及其附件损害最多,有158例(占42.36%);由于不合理用药而导致的ADR有175例,占50.43%,其中,剂量选择错误是主要原因,无感染指征用药、选药不当、联合用药不合理、溶媒选择错误均占有一定比例。175例不合理用药导致的ADR中,头孢菌素类抗生素所占比例最高,占46.29%。结论:抗菌药物致ADR的发生与多种因素有关,临床应重视抗菌药物的合理使用,警惕可能由于抗菌药物的不合理使用而诱发的严重ADR,从而合理、规范地使用抗菌药物,减少ADR的发生。     

某三甲医院近三年抗菌药物不良反应研究

目的 分析某三甲医院近三年抗菌药物不良反应（ADR）的发生规律与特点,探讨其原因及预防措施,为临床合理使用抗菌药物提供参考。方法 从该院ADR监测系统中筛选出2019—2021年上报的抗菌药物ADR报告,对其进行回顾性统计分析。结果 在该院近三年上报的216例抗菌药物ADR报告中,报告类型为新的及严重的ADR共有113例,占比52.31%;ADR发生时间多在用药后2～5 d内,占比42.60%;男性发生ADR的比例高于女性（58.80%vs. 41.20%）,差异无统计学意义（P> 0.05）。61～80岁的患者ADR发生率最高,占比36.57%;抗结核药物ADR发生位居首位,占比51.50%,其次为头孢菌素类,占比16.00%;静脉给药引发的ADR比例最高,占比44.25%,口服给药次之,占比43.00%;皮肤及其附件损害在抗菌药物ADR中最为常见,占比36.62%;发生ADR后大多数患者都能好转或痊愈,占比93.06%。结论 临床应对抗结核类、头孢菌素类、喹诺酮类抗菌药物的ADR进行重点监测。在抗菌药物使用中应加强对高龄患者的用药监护,减少静脉给药,做到能口服则不静脉用药,密...     

我院2002年~2005年311例药品不良反应报告分析

目的:了解我院药品不良反应(ADR)的发生特点及评价ADR报告填写质量,促进临床合理用药。方法:制作Excel表,对2002年~2005年收集到的311例ADR根据患者性别、年龄及药品种类、ADR临床表现等分类,并进行统计分析。结果:由抗菌药物导致的ADR所占比例最高;皮肤及其附件损害的ADR约为总报告例次的50%;ADR报告总数偏少。结论:应加强专业人员的业务和素质培养,合理使用抗菌药物,以减少和避免ADR的发生。     

37例药物不良反应报告分析

目的分析蛟河市白林医院临床科室2008年至2009年上报的37例药物不良反应(ADR)报告情况,为临床医师和药师及时判断与减少ADR的发生提供数据资料的参考。方法采用调查方法,对ADR报告中涉及的患者年龄、药品种类、联合用药、给药途径、临床表现和转归情况进行统计分析。结果引起ADR的药品主要集中于抗菌药物,占总数的56.76%(21/37),其中抗菌药物注射剂引起的ADR占抗菌药物总数的71.43%(15/21),37例ADR中32.43%为联合用药,外用药品引起的ADR占总数的24.32%(9/37),其他药品引起的ADR占总数的18.9%。结论医务人员应加强对ADR的认知,规范用药操作过程,合理联合用药,减少药品对患者可能造成的伤害。     

抗菌药物不良反应报告140例分析

目的分析该院抗菌药物不良反应报告,研究抗菌药物不良反应发生特点,为临床合理用药提供依据。方法采用回顾性分析方法对该院140例抗菌药物不良反应报告进行统计分析与评价,归纳总结抗菌药物不良反应发生的一般规律和特点。结果 140例药物不良反应（ADR）报告中,≥60岁发生率最高占52.86%;静脉滴注给药引发不良反应发生率较高（92.86%）;头孢菌素类药物（30.00%）引起的ADR居首位,其次为喹诺酮类（25.00%）;ADR的临床表现主要为皮肤及其附件损害（51.43%）,其次是消化系统（17.14%）及神经系统（12.86%）损害。结论抗菌药物不良反应发生与多种因素相关,应重视ADR的监测工作,合理应用抗菌药物,避免和减少ADR的发生。     

65例药品不良反应报告表分析

目的为了深入开展药品不良反应(ADR)的报告和监测工作,进一步提高ADR工作水平,提高合理用药水平。方法对我院2012年上报65例ADR报表中分别从科室上报数量、患者的年龄、性别、涉及药品的类别、主要临床表现等方面进行统计分析。结果科室上报数量以皮肤科最多,患者中男性36例,占总数55.38%;女性29例,占总数45.62%;怀疑ADR的药品共43种,抗菌药物引起的ADR的药物种类最多,频次最多,发生26例,占40%,。中药制剂引发ADR的发生12例,占18.46%。抗肿瘤药引发ADR发生7例,占10.77%;引起ADR涉及的系统及主要症状以皮肤及附件为主,占到50.77%。抗菌药物引起ADR最多是大环内脂类,发生7例。结论提高对ADR的监测与上报,及时分析ADR的信息,采取及时有效的对症措施,从中发现有价值的信息,达到临床安全用药的目的。     

某院181例儿童药品不良反应报告分析

目的:了解某院儿童药品不良反应(ADR)发生的特点及规律,促进临床合理用药。方法:采用回顾性研究方法,对该院2012年收集并上报的181例儿童ADR报告进行统计、分析。结果:181例ADR报告中,男性多于女性,>1³岁患儿比例最高(29.83%);ADR涉及药品种类有34种,抗感染药物占13个品种(124例,占68.51%);静脉给药引发的ADR为168例;引起皮肤及附件损害的ADR最多,有121例;严重ADR占19.89%,主要表现为过敏性休克,其中抗菌药物所致严重ADR最多(44.44%)。结论:医院应重视儿童临床用药的合理性,加强儿童药品不良反应监测,减少ADR的发生。     

Hsp90 inhibitor BILBO21 enhances triptolide-induced apoptosis of human T-cell acute lymphoblastic leukemia cells in vitro mainly by disrupting p53- MDM2 balance

Aim： To investigate the effects of BILBO21, an inhibitor of heat shock protein 90 （Hsp90） alone or in combination with triptolide （TPL） on T-cell acute lymphoblastic leukemia （T-ALL） and the mechanisms of action. Methods： Human T-ALL cells line Molt-4 was examined. The cell viability was measured using M]-I- assay. Apoptotic cells were studied with Hoechst 33258 staining. Cell apoptosis and cell cycle were analyzed using flow cytometry with Annexin V/PI staining and PI staining, respectively. The levels of multiple proteins, including Akt, p65, CDK4/6, p18, Bcl-2 family proteins, MDM2, and p53, were examined with Western blotting. The level of MDM2 mRNA was determined using RT-PCR. Results： Treatment of Molt-4 cells with BILBO21 （50-800 nmol/L） inhibited the cell growth in a dose-dependent manner （the IC~ovalue was 384.6 and 301.8 nmol/L, respectively, at 48 and 72 h）. BILBO21 dose-dependently induced Go/G1 phase arrest, followed by apoptosis of Molt-4 cells. Furthermore, BILBO21 increased the expression of p18, decreased the expression of CDK4/6, and activated the caspase pathway in Molt-4 cells. Moreover, BILBO21 （50-400 nmol/L） dose-dependently decreased the phospho-MDM2 and total MDM2 protein levels, but slightly increased the phospho-p53 and total p53 protein levels, whereas TPL （5-40 nmol/L） dose- dependently enhanced p53 activation without affecting MDM2 levels. Co-treatment with BILBO21 and TPL showed synergic inhibition on Molt-4 cell growth. The co-treatment disrupted p53-MDM2 balance, thus markedly enhanced p53 activation. In addition, the co-treatment increased the expression of Bak and Bim, followed by increased activation of caspase-9. Conclusion： The combination of BILBO21 and TPL may provide a novel strategy for treating T-ALL by overcoming multiple mechanisms of apoptosis resistance.     

我院2010年药品不良反应监测分析

目的了解该院药品不良反应(ADR)发生情况,促进临床合理用药。方法对该院2010年收集到的806份ADR报告进行分类统计和分析评价。结果 806份ADR中,老年患者较多,占总例数的39.1%(316例);以静脉滴注方式给药引发的ADR最多,占总例数的93%(749例);抗菌药引起的ADR最多,占总例数的40.69%(328例);临床表现以消化系统损伤最常见,占总例数的39.2%(316例)。结论继续做好并加强ADR监测工作,避免或减少ADR发生。     

美国与欧洲上市后药品安全风险管理进展概述

近10年来,美国食品药品管理局（FDA）、欧洲药品管理局（EMA）及其他相关单位,对上市后药品安全性监测日益重视,在这一领域取得了显著进展,并且制定了一系列新规定。     

Prenatal nicotine exposure enhances the susceptibility to metabolic syndrome in adult offspring rats fed high-fat diet via alteration of HPA axis-associated neuroendocrine metabolic programming

Aim： Prenatal nicotine exposure （PNE） alters the hypothalamic-pituitary-adrenocortical （HPA） axis-associated neuroendocrine metabolic programming in intrauterine growth retardation offspring rats. In this study we aimed to clarify the susceptibility to metabolic diseases of PNE offspring rats fed a high-fat diet. Methods： Maternal Wistar rats were injected with nicotine （1.0 mg/kg, sc） twice per day from gestational day 11 until full-term delivery, and all pups were fed a high-fat diet after weaning and exposed to unpredictable chronic stress （UCS） during postnatal weeks 18-20. Blood samples were collected before and after chronic stress, and serum ACTH, corticosterone, glucose, insulin, total cholesterol, triglyceride and free fatty acids levels were measured. The hypothalamus, pituitary gland and liver were dissected for histological studies. Results： UCS significantly increased the serum ACTH, corticosterone and insulin levels as well as the insulin resistant index without changing the serum glucose, total cholesterol, triglyceride and free fatty acids levels in adult offspring rats without PNE. The body weight of PNE offspring rats presented a typical ＂catch-up＂ growth pattern. PNE not only aggravated the UCS-induced changes in the HPA axis programmed alteration （caused further increases in the serum ACTH and corticosterone levels）, but also significantly changed the glucose and lipid metabolism after UCS （caused further increases in the serum glucose level and insulin resistant index, and decrease in the serum free fatty acids）. The effects of PNE on the above indexes after UCS showed gender differences. Pathological studies revealed that PNE led to plenty of lipid droplets in multiple organs. Conclusion： PNE enhances not only the HPA axis, but also the susceptibility to metabolic diseases in adult offspring rats fed a high-fat diet after UCS in a gender-specific manner and enhances the susceptibility to metabolic diseases in adult offspring rats fed a high-fat diet.     

Stereoselective binding of doxazosin enantiomers to plasma proteins from rats,dogs and humans in vitro

Aim： （＋）Doxazosin is a long-lasting inhibitor of a1-adrenoceptors that is widely used to treat benign prostatic hyperplasia and lower urinary tract symptoms. In this study we investigated the stereoselective binding of doxazosin enantiomers to the plasma proteins of rats, dogs and humans in vitro. Methods： Human, dog and rat plasma were prepared. Equilibrium dialysis was used to determine the plasma protein binding of each enantiomer in vitro. Chiral HPLC with fluorescence detection was used to measure the drug concentrations on each side of the dialysis membrane bag. Results： Both the enantiomers were highly bound to the plasma proteins of rats, dogs and humans [（-）doxazosin： 89.4%-94.3%; （＋）doxazosin： 90.9%-95.4%]. （＋）Doxazosin exhibited significantly higher protein binding capacities than （-）doxazosin in all the three species, and the difference in the bound concentration （Cb） between the two enantiomers was enhanced as their concentrations were increased. Although the percentage of the plasma protein binding in the dog plasma was significantly lower than that in the human plasma at 400 and 800 ng/mL, the corrected percentage of plasma protein binding was dog〉human〉rat. Conclusion： （-）Doxazosin and （＋）doxazosin show stereoselective plasma protein binding with a significant species difference among rats, dogs and humans.     

Molecular modeling,quantum polarized ligand docking and structure-based 3D-QSAR analysis of the imidazole series as dual AT~ and ETA receptor antagonists

Aim： Both endothelin ETA receptor antagonists and angiotensin AT1 receptor antagonists lower blood pressure in hypertensive patients. A dual AT1 and ETA receptor antagonist may be more efficacious antihypertensive drug. In this study we identified the mode and mechanism of binding of imidazole series of compounds as dual AT1 and ETA receptor antagonists. Methods： Molecular modeling approach combining quantum-polarized ligand docking （QPLD）, MM/GBSA free-energy calculation and 3D-QSAR analysis was used to evaluate 24 compounds as dual AT1 and ETA receptor antagonists and to reveal their binding modes and structural basis of the inhibitory activity. Pharmacophore-based virtual screening and docking studies were performed to identify more potent dual antagonists. Results： 3D-QSAR models of the imidazole compounds were developed from the conformer generated by QPLD, and the resulting models showed a good correlation between the predicted and experimental activity. The visualization of the 3D-QSAR model in the context of the compounds under study revealed the details of the structure-activity relationship： substitution of methoxymethyl and cyclooctanone might increase the activity against AT~ receptor, while substitution of cyclohexone and trimethylpyrrolidinone was important for the activity against ETA receptor; addition of a trimethylpyrrolidinone to compound 9 significantly reduced its activity against AT~ receptor but significantly increased its activity against ETA receptor, which was likely due to the larger size and higher intensities of the H-bond donor and acceptor regions in the active site of ETA receptor. Pharmacophore-based virtual screening followed by subsequent Glide SP, XP, QPLD and MM/GBSA calculation identified 5 potential lead compounds that might act as dual AT1 and ETA receptor antagonists. Conclusion： This study may provide some insights into the development of novel potent dual ETA and AT1 receptor antagonists. As a result, five compounds are found to be the best dual antagonists against AT1R and ETA receptors.     

A new bisphosphonate derivative,CP, induces gastric cancer cell apoptosis via activation of the ERK1/2 signaling pathway

Aim： To investigate the effects of a new derivative of bisphosphonates, [2-（6-aminopurine-9-yl）-l-hydroxy-phosphine acyl ethyl] phosphonic acid （CP）, on human gastric cancer. Methods： Human gastric cancer cell lines （SGC-7901, BGC-823, MKN-45, and MKN-28） and human colon carcinoma cell lines （LoVo and HT-29） were tested. Cell growth was determined using the MTT assay. Flow cytometry, Western blot, caspase activity assay and siRNA transfection were used to examine the mechanisms of anticancer action. Female BALB/c nude mice were implanted with SGC- 7901 cells. From d6 after inoculation, the animals were injected with CP （200 pg/kg, ip） or vehicle daily for 24 d. Results： CP suppressed the growth of the 6 human cancer cell lines with similar IC5o values （3239 pmol/L）. In SGC-7901 cells, CP arrested cell cycle progression at the G2/M phase. The compound activated caspase-9, increased the expression of pro-apoptotic proteins Bax and Bad, decreased the expression of anti-apoptotic protein Bcl-2. Furthermore, the compound selectively activated ERK1/2 without affecting JNK and p38 in SGC-7901 cells. Treatment of SGC-7901 cells with the specific ERK1/2 inhibitor PD98059 or ERK1/2 siRNA hampered CP-mediated apoptosis. In the human gastric cancer xenograft nude mouse model, chronic administration of CP significantly retarded the tumor growth. Conclusion： CP is a broad-spectrum inhibitor of human carcinoma cells in vitro, and it also exerts significant inhibition on gastric cancer cell growth in vivo. CP induces human gastric cancer apoptosis via activation of the ERK1/2 signaling pathway.     

Oligomannurarate sulfate inhibits CXCL12/SDF-1- mediated proliferation and invasion of human tumor cells in vitro

Aim： JG6 is a novel marine-derived oligosaccharide that has shown to inhibit angiogenesis and tumor metastasis. In this study, we sought to identify the potential target responsible for the anti-cancer activity of JG6. Methods： Human liver cancer cell line Bel-7402 and human cervical cancer cell line HeLa were examined. CXCL12-stimulated cell proliferation and migration were determined using a CCK-8 kit and a transwell assay, respectively. Western blotting was performed to examine the changes in CXCL12/CXCR4 axis. Molecular docking and surface plasmon resonance （SPR） were performed to characterize the possible interaction between JG6 and the CXCL12/CXCR4 axis. Results： Treatment with CXCL12 potently stimulated the proliferation and migration in both Bel-7402 and HeLa cells. Co-treatment of the cells with JG6 （10, 50 and 100 pp=VmL） dose-dependently impeded the CXCL12-stimulated cell proliferation and migration. Furthermore, CXCL12 rapidly induced phosphorylation of AKT, ERK, FAK and Paxillin in Bel-7402 and HeLa cells, whereas pretreatment with JG6 dose-dependently inhibited the CXCL12-induced phosphorylation of these proteins. The SPR assay showed that JG6 bound to CXCL12 with a high affinity. In molecular docking study, JG6 appeared to interact with CXCL12 via multiple polar interactions, including 6 ionic bonds and 7 hydrogen bonds. Conclusion： Inhibition of the CXCL12/CXCR4 axis by JG6 may account for its anticancer activity.     

DNA aptamers that target human glioblastoma multiforme cells overexpressing epidermal growth factor receptor variant III in vitro

Aim： Aptamers are oligonucleic acid or peptide molecules that bind to a specific target molecule in cells, thus may act as effective vehicles for drug or siRNA delivery. In this study we investigated the DNA aptamers that target human glioblastoma multiforme （GBM） cells overexpressing epidermal growth factor receptor variant III （EGFRvlII）, which was linked to radiation and chemotherapeutic resistance of this most aggressive brain tumor. Methods： A 73-mer ssDNA library containing molecules with 30 nt of random sequence flanked by two primer hybridization sites was chosen as the initial library. Cell systematic evolution of ligands by exponential enrichment （CelI-SELEX） method was used to select the DNA aptamers that target EGFRvlII. The binding affinity of the aptamers was measured using a cell-based biotin-avidin ELISA. Results： After 14 rounds of selection, four DNA aptamers （32, 41, 43, and 47） that specifically bound to the EGFRvlll-overexpressing human glioma U87A cells with K~ values of less than 100 nmol/L were discovered. These aptamers were able to distinguish the U87A cells from the negative control human glioma U87MG cells and HEK293 cells. Aptamer 32 specifically bound to the EGFRvlII protein with an affinity similar to the EGFR antibody （Kd values of aptamer 32 and the EGFR antibody were 0.62±0.04 and 0.32±0.01 nmol/L, respectively）, and this aptamer was localized in the cell nucleus. Conclusion： The DNA aptamers are promising molecular probes for the diagnosis and treatment of GBM.