Gut microbiota-mediated metabolism of Panax notoginseng saponins and its role in pharmacokinetics and pharmacodynamics

Panax notoginseng saponins(PNS)are a class of effective ingredients in Notoginseng Radix et Rhizoma,a well-known herbal medicine called San-Qi in Chinese.After oral administration,PNS inevitably interacts with gut microbiota,and thus affect the pharmacokinetic profiles and pharmacological effects.To date,studies concering gut microbiota-mediated metabolism of PNS have not been reviewed systematically.Herein,we outline the metabolic profiles of Panax notoginseng saponins mediated by gut microbiota,as well as its role in the pharmacokinetics and pharmacodynamics on the basis of reported data.The metabolic pathways of primary saponins are proposed,and step-by-step deglycosylation is found to be the primary degradation pathways of PNS mediated by gut microbiota.Specific microorganisms and enzymes involved in the metabolic processes were summarized.Gut microbiota is deeply involved in the metabolism of PNS,affects the pharmacokinetic profiles,and produces a series of active metabolites.These metabolites were documented to play an essential role in the efficacy of the parent compounds.Future studies should focus on strengthening the real-world evidence,defining the interaction between gut microbiota and PNS,and developing the strategy for modulating gut microbiota to enhance the bioavailability and efficacy of PNS.These information would be useful for further research and clinical application of PNS.

To explore the mechanism of Fuyang Jiebiao granules against viral pneumonia based on network pharmacology and pharmacodynamics

Objective:To investigate the mechanism of Fuyang Jiebiao granule(FYJBKL)in the treatment of viral pneumonia.Methods:Firstly,a network model was constructed using network pharmacology to study the target expression sites of FYJBKL viral pneumonia,so as to determine the main targets and important signal transduction pathways for the treatment of viral pneumonia.Secondly,the main components of the drug and the main target are docked.Then,the fever,sweating and inflammation rat models were established to explore the antipyretic,sweating and anti-inflammatory mechanisms of FYJBKL.Finally,the contents of IL-17,IL-1β,TNF-αand IL-6 in blood samples of rats were analyzed by ELISA method,and the morphological changes of lung tissue were observed by HE staining.Results:Quercetin,luteolin,kaempferol,etc.,and the main mechanism targets are IL-17,IL-1β,TNF-α,IL-6 and so on.Thirty signal pathways were identified by KEGG enrichment analysis,including interleukin-17 signaling pathway(IL-17 signaling pathway),human cytomegalovirus infection pathway(human cytomegalovirus infection),Kaposi's sarcoma associated herpesvirus infection pathway(Kaposi's sarcoma-as-sociated herpesvirus infection)and so on.After the study of molecular docking,we found that the contact efficiency between active substances and possible key targets is good.The high and middle concentration groups of FYJBKL significantly decreased the expression of IL-17,IL-1β,TNF-αand IL-6 in the blood of rats with inflammation(P<0.05).FYJBKL significantly reduced the foot swelling induced by egg white and inhibited the increase of body temperature induced by yeast in rats(P<0.05).HE staining showed that FYJBKL improved pulmonary fibrosis and inflammatory exudation to varying degrees.Conclusion:The effects of FuyangJiebiao granules on the related signal pathways of anti-virus,anti-immune and anti-inflammation as well as biological and cellular processes may be caused by the binding of quercetin,luteolin,kaempferol and other active ingredients to their shared targets.Fuyang Jiebiao granules can improve the related symptoms caused by viral pneumonia,and its mechanism may be related to the activities of TNF,IL-17,IL-6 and other related channels,which are multiple targets of inflammation regulation.

Interest of Transcranial Doppler (TCD) in Emergency in Traumatic Brain Injury Patients at Gabriel Touré University Hospital, Bamako, Mali

Introduction: Transcranial Doppler is a simple, non-invasive and inexpensive examination which allows the assessment of cerebral perfusion. In countries with limited resources, which do not have a means of monitoring intracranial pressure, this examination offers hope of survival for patients with traumatic brain injury. This study was designed to investigate the incidence of early cerebral circulation abnormalities after traumatic brain injury using transcranial Doppler (TCD). Methodology: A descriptive and analytical study was conducted over one year, including patients with traumatic brain injury and an initial Glasgow Coma Scale (GCS) score of less than 15. Non-inclusion criteria: Stroke, brain tumor, cerebral abscess. Exclusion criteria: Inadequate insonation window. Results: Out of 854 traumatic brain injury patients admitted to the emergency department, 112 were included in the study. The average age was 30.14 years, with a sex ratio of 4.1. Initially, 83.5% had moderate traumatic brain injury, and 12.1% had severe traumatic brain injury. Brain CT scans were performed in 95.7% of the patients. Edematous-hemorrhagic contusion was observed in 95% of the patients. On initial TCD, the pulsatility index in the middle cerebral artery was greater than 1.3 in 49.4% of the patients. Diastolic velocity was less than 20 cm/s in 46.4% of cases, and mean velocity was greater than 150 cm/s in 8.7% of cases. In this group, low diastolic velocity indicated cerebral hypoperfusion suggestive of intracranial hypertension. When the pulsatility index was greater than 1.9, no patient had a normal diastolic velocity. Among patients with severe traumatic brain injury, 61.5% had an abnormal pulsatility index compared to 42.3% of patients with moderate traumatic brain injury. Conclusion: TCD is a simple tool for analyzing intracerebral hemodynamics.

超声联合TCD技术诊断颈部动脉粥样硬化性脑梗死的临床价值

目的:探讨超声联合TCD技术诊断颈部动脉粥样硬化性脑梗死(CAEI)的临床价值。方法:以62例CAEI患者为对象,以同期62例健康人为对照组。均接受血管超声及TCD检查,分析二者诊断CAEI的价值。结果:观察组颈总动脉收缩期内径(Ds)、内中膜厚度(IMT)值高于对照组(P<0.05)。观察组Vd、Vs低于对照组,RI、PI高于对照组(P<0.05)。观察组斑块检出率为85.48%,高于对照组(19.35%,P<0.05)。模型1(Ds+IMT)诊断CAEI的AUC、灵敏度、特异度分别为0.754(95%CI:0.669-0.827)、79.03%、74.19%;模型2(Vs+Vd+RI+PI)诊断CAEI的AUC、灵敏度、特异度分别为0.814(95%CI:0.735-0.878)、82.26%、70.97%;模型3(Ds+IMT+Vs+Vd+RI+PI)诊断CAEI的AUC、灵敏度、特异度分别为0.871(95%CI:0.799-0.924)、90.32%、74.19%。模型3诊断CAEI的AUC高于模型1、模型2(P<0.05)。结论:超声联合TCD检测可了解CAEI患者的颈动脉斑块及血流信息,有助于提高诊断的准确度。

TCD监测颅内血流动力学参数评估脑血管病患者颈动脉狭窄程度及神经功能恶化的风险

目的探讨经颅射绝超声多普勒系统(TCD)监测颅内血流动力学对脑血管病患者颈动脉狭窄严重程度和神经功能恶化风险的评估价值。方法前瞻性纳入122例脑血管病患者为病例组,根据患者颈动脉狭窄程度分为轻度狭窄组(n=43)、中度狭窄组(n=47)、重度狭窄组(n=32),并纳入同期健康体检者60例为对照组,比较4组颅内血流动力学指标,并采用Pearson分析其与患者颈动脉狭窄严重程度的相关性;根据患者神经功能恶化程度分为神经功能恶化组(n=55)和神经功能未恶化组(n=67),采用单因素和多因素Logistic回归分析明确影响患者发生神经功能恶化的高危因素,并采用受试者工作特征(ROC)曲线进一步分析独立危险因素对神经功能恶化的诊断效能。结果轻、中、重度狭窄组舒张期峰值血流速度(EDV)、收缩期峰值血流速度(PSV)及平均血流速度(MV)水平均较对照组偏低,搏动指数(PI)和阻力指数(RI)较对照组偏高,有统计学差异(P<0.05);重度狭窄组PSV、MV、EDV水平较轻、中度狭窄组显著偏低,PI及RI水平显著偏高(P<0.05)。Pearson相关性分析结果显示,PSV、EDV及MV与颈动脉狭窄程度呈显著正相关(r=0.541,0.763,0.822,均P<0.05),PI及RI与颈动脉狭窄程度呈显著负相关(r=-0.133,-0.375,均P<0.05)。神经功能恶化组平均年龄、入院GCS评分、ICU停留时间及住院时长等临床指标均明显高于神经功能未恶化组(P<0.05);两组大脑中动脉血流动力学参数对比,神经功能恶化组收缩期血流速度(FVs)、PI显著高于神经功能未恶化组,FVd、平均流速(FVm)明显低于神经功能未恶化组(P<0.05)。Logistic回归分析结果显示,ICU停留时间、住院时间、FVs、舒张期血流速度(FVd)、PI均是影响脑血管病患者神经功能恶化的独立危险因素(P<0.05)。ROC曲线分析结果显示,FVs、FVd、FVm及PI对预测脑血管病患者发生神经功能的ROC曲线下面积(AUC)分别为0.643、0.834、0.336、0.866(均P<0.05)。诊断效能:PI>FVd>FVs>FVm。结论应用TCD对脑血管病患者颅内血流动力学参数进行监测可辅助临床评估患者的颈动脉狭窄程度,对此类患者发生神经功能病变具有较高的预测价值。

TCD发泡试验在诊断隐源性脑卒中相关危险因素PFO中的应用研究

研究TCD发泡试验在隐源性脑卒中中相关危险因素PFO应用效果开展诊断评估。方法 选择我院2019-2023年所接受到的80名隐源性脑卒中患者为分析对象,比较患者经颅多普勒超声(TCD)发泡试验和经胸心脏超声心动图(TTE)检查结果阳性率和影像学特征。结果 TCD发泡试验在隐源性脑卒中相关危险因素卵圆孔未闭(PFO)阳性率检出率和TTE阳性检出率检查方面,检查具备统计学意义。在TCD发泡试验对隐源性脑卒中脑卒中相关危险因素中PFO阳性和阴性患者检查内,阳性患者梗死病大部分出现在皮层、皮层下区域,阴性患者主要出现深部灰质区域。结论 TCD发泡试验可以有效检测出由于PFO该危险因素造成隐源性脑卒中,PFO阳性病灶大部分位于皮层、皮层下区域,就隐源性脑卒中相关危险因素PFO筛查、诊断、病因研究等角度具备关键意义,适宜临床推广与应用。

TCD发泡试验在卵圆孔未闭中的应用

对卵圆孔未闭采用TCD发泡实验,做好效果分析。方法 通过选取本院收治的隐源性卒中患者42例,患者在入院后进行MRI以及CT检查,采用TCD发泡实验,做好阳性率情况的比较。结果 通过对42例患者进行检查,其中阳性率为88.4%。卵圆孔直径在1-3mm之间。结论 对卵圆孔未闭采用TCD发泡实验,能够更好的探查卒中,明确隐源性脑梗的发生概率,整体效果良好,为患者预后提供一定基础。

TCD5 Enhances the Photosynthesis Capacity,Increases the Panicle Number and the Yield in Rice

Improvement of photosynthetic efficiency is a major approach to increase crop yield potential.Previously,we cloned a gene encoding the chloroplast-located putative monooxygenase TCD5,which is essential in plastid development under low temperature in rice(Oryza sativa L.).In this study,the effects of TCD5 on the photosynthesis and the yields were investigated in rice.Two sets of genetic materials with three levels of TCD5 expression,including tcd5 mutant or TCD5 RNAi transgenic lines and TCD5 over-expression transgenic lines in Jiahua1 and Nipponbare backgrounds,were used in the field trails of multi-locations and multi-years.TCD5 positively affected the panicle number and the yield at dosage.Compared with the wild-types,the panicle numbers were 12.4%-14.6%less in tcd5 mutant and 8.3%-38.6%less in TCD5 RNAi lines,but 26.2%-61.8%more in TCD5 over-expression lines.The grain yields per plant were 9.1%-18.4%less in tcd5 mutant and 14.3%-56.7%less in TCD5 RNAi lines,but 6.9%-56.5%more in TCD5 over-expression lines.The measurements of net photosynthetic rate indicated that mutation or knock down of TCD5 decreased the net photosynthetic rate by 10.4%and 15.6%,respectively,while increasing it by 8.9%and 8.7%in the TCD5 over-expression lines in Jiahua1 and Nipponbare backgrounds,respectively.Accordingly,the measurements of chlorophyll fluorescence parameters showed that the electron transport rate and quantum yield decreased in tcd5 mutant or TCD5 RNAi lines but increased in TCD5 overexpression lines,both in Jiahua1 and Nipponbare backgrounds.IP-MS screening revealed that TCD5 interacts with 29 chloroplast proteins involved in chlorophyll synthesis,photo-reactions of the photosynthesis,carbon assimilation and metabolism,energy metabolism,redox balance,protein synthesis and transportation.Two TCD5 interacted proteins,D1 and FBA were effective targets for improving photosynthesis.These results suggest a potentially new strategy for increasing rice yield by enhancing photosynthesis.

Anorectal Pharmacodynamics and In Vitro Drug Release of Clerodendrum bungei Steud.Extract Gel

[Objectives]To determine the optimal preparation technology of Clerodendrum bungei Steud.extract gel by orthogonal test and gel quality test method in General Rule 0114 of Chinese Pharmacopoeia(Volume IV,2020 Edition),and to study its anorectal pharmacodynamics and drug release in vitro.[Methods]Carbomer 940,propylene glycol and absolute ethyl alcohol were selected as the main factors,and the preparation technology of C.bungei Steud.extract gel was optimized by orthogonal test.The mouse model of ulcerative hemorrhoids was established with glacial acetic acid(HAC)and compared with Ma Yinglong musk hemorrhoids ointment.The recovery of trauma was compared between the two groups.At the same time,porcine small intestine was used as semi-permeable membrane to make diffusion cell to simulate anal environment,and the drug release in vitro was studied.[Results]The C.bungei Steud.extract gel was smooth in appearance and good in stability.It could effectively treat anal ulcer in mice and release quickly in vitro.[Conclusions]The formula is reasonable,and the effect of animal experiment is remarkable,which can provide a new treatment plan for ulcerative hemorrhoids.

Pharmacokinetics/Pharmacodynamics study of Fixtral SB as compared to supra bioavailable itraconazole and conventional itraconazole

BACKGROUND Itraconazole is a broad-spectrum triazole antifungal inhibiting fungal growth by inhibiting ergosterol synthesis and exhibits a nonlinear pharmacokinetic profile.Erratic absorption pattern with wide fluctuations in blood levels causes inconsistent and unpredictable clinical behaviour of this drug despite its low minimum inhibitory concentration(MIC)as compared to other antifungal agents.AIM To compare the oral bioavailability and bioequivalence of Fixtral SB(supra bioavailable itraconazole)with reference product R2(supra bioavailable 2×50 mg itraconazole).METHODS The study population consisted of 54 healthy volunteers,aged between 18-45 years and randomized to receive a single oral dose of either test[T;Fixtral SB(supra bioavailable itraconazole)100 mg]or reference product(R1;Sporanox 100 mg×2 capsules and R2;Lozanoc capsules 50 mg×2 capsules).Blood samples were taken pre-dose and post-dose up to 96 h.The study evaluated bioequivalence by comparing the oral bioavailability of the test product with reference product R2.The pharmacodynamic characteristics of the drug were evaluated by comparing the test product with reference product R1.Pharmacokinetics(PK)-PD comparative analysis[area under the concentration-time curve(AUC)/minimum inhibitory concentration(MIC)>25]was performed for conventional itraconazole 100 mg and supra bioavailable itraconazole 50 mg.Adverse events(AEs)assessments were performed in each study period and post-study evaluation.RESULTS Statistical analysis of primary PK variables revealed bioequivalence,with confidence intervals being completely inside the acceptance criteria of 80%-125%.The peak concentration levels of itraconazole were achieved at 10 h(T)and 8.5 h(R2),respectively.Pharmacodynamic parameter assessment showed that AUC/MIC for R1 are comparable to Fixtral SB 100mg for MIC levels up to 16mcg/mL(P>0.05 and observed P=0.3196).Six AEs were observed that were mild to moderate in severity and resolved.No severe AE was reported.CONCLUSION Test product itraconazole Capsule 100 mg is bioequivalent with the reference product(R2)at 100 mg dose(2 capsules of Lozanoc®50 mg)under fed conditions.Pharmacodynamics activity in terms of AUC/MIC is comparable between the test product at 100 mg dose and marketed itraconazole 200 mg.Fixtral SB is expected to have therapeutically similar efficacy at half the equivalent dose.Tested formulations were found to be safe and well tolerated.

托莫西汀联合感觉统合训练治疗注意缺陷多动障碍患儿效果及对TCD参数、动态肌电图的影响

目的:探讨托莫西汀联合感觉统合训练治疗注意缺陷多动障碍(ADHD)患儿效果及对经颅多普勒超声检查(TCD)参数、动态肌电图的影响。方法:按随机数字表法将2021年9月至2022年9月我院收治的60例ADHD患儿分为两组,各30例。对照组采用托莫西汀治疗,研究组在对照组基础上加用感觉统合训练治疗,对比两组临床疗效、TCD参数[大脑基底动脉(BA)、左侧中动脉(MCA-L)、左侧前动脉(ACA-L)、左侧后动脉(PCA-L)]、儿童感觉统合能力发展评定量表评分、中文版注意缺陷多动障碍评定量表-父母版(SNAP-IV)评分和不良反应。结果:研究组治疗后总有效率高于对照组(P<0.05);两组治疗后BA对比,无统计学差异(P>0.05);研究组治疗后MCA-L、ACA-L、PCA-L高于对照组(P<0.05);研究组治疗后儿童感觉统合能力发展评定量表评分高于对照组(P<0.05);研究组治疗后SNAP-IV评分低于对照组(P<0.05);两组治疗期间均无严重不良反应发生。结论:托莫西汀联合感觉统合训练可有效提升ADHD患儿的注意力和感觉统合能力,促进大脑动脉局部灌注的恢复,利于纠正患儿行为抑制缺陷,值得在临床上推广和应用。

TCD发泡试验在肝硬化门静脉高压患者中的临床价值探讨

探讨经颅多普勒(transcranialDoppler,TCD)发泡试验在肝硬化门静脉高压患者中的临床价值。方法 收集2021年5月~2023年4月玉林市红十字会医院消化内科收治肝硬化门静脉高压患者141例作为观察组,选择同期门诊就诊健康体检者58例作为对照组,两组均进行发泡试验,记录观察组和对照组发泡试验阳性率并对比分析,同时将肝硬化门静脉高压伴和不伴食管胃静脉曲张出血的发泡试验阳性率、不同肝功能分级发泡试验阳性率进行比较,分析其差异性。结果 门静脉高压患者发泡试验阳性率高于健康者,差异有统计学意义(P<0.05)。食管胃底静脉曲张破裂出血发泡试验阳性率低于非食管胃底静脉曲张破裂出血,P<0.05。结论 在肝硬化门静脉高压患者中,进行TCD发泡试验具有临床应用的价值。该试验可以作为一种新的指导方法,用于在内镜下治疗食管胃底静脉曲张破裂出血时提供指导。

偏头痛患者采用TCD发泡试验筛查卵圆孔未闭的价值分析与探讨

探讨分析偏头痛患者的TCD发泡试验筛查卵圆孔未闭的临床表现,针对偏头痛患者的卵圆孔功能进行判断,为患者的诊断提供进一步的参考方案。方法 本次研究在进行实验设置时,选择实验时间段为2019年6月,至2022年3月,研究人员在该时段内将我院资料登记有效的偏头痛患者共计80名作为研究对象,选择同期内院中接受健康体检的成人共计80名作为对照对象。研究人员在针对所有患者的一般资料进行记录后,针对患者进行TCD发泡试验筛查卵圆孔未闭检查,诊断完成后,研究人员针对患者的TCD发泡试验筛查卵圆孔未闭指标进行评价,分析组间差异。结果 在本次研究结果中显示,相较于对照组来说,实验组内患者的TCD发泡试验筛查卵圆孔未闭结果中发生率明显更高,数据进行对比分析后,差异显著,具有统计学意义(P<0.05)。结论 偏头痛患者的TCD发泡试验可以用于筛查卵圆孔未闭。在本次结果中表明卵圆孔未闭与偏头痛之间存在相关性。这项检查可以为偏头痛患者的诊断提供重要的参考信息,特别是在考虑手术干预或其他治疗方案时。TCD发泡试验可用于评估偏头痛患者的卵圆孔功能和筛查卵圆孔未闭。这一方法对于指导偏头痛患者的诊断和治疗决策具有重要的临床意义。

万古霉素在重症感染中的治疗药物监测现状及前景

万古霉素被誉为治疗革兰阳性菌感染的最后一道防线,也是推荐的一线用药。因其治疗窗窄,重症患者需监测药物浓度以指导临床安全用药。传统上基于万古霉素谷浓度的治疗药物监测已被临床广泛接受。2009年美国传染病学会(IDSA)指南建议,对于重症患者目标谷浓度为15~20 mg/L。近十余年国内外学者对于该治疗浓度的安全性及有效性评价不一。2020年更新指南提出,肾损伤风险最小、最准确且最佳的给药方法是通过曲线下面积(AUC)指导给药剂量和监测,提倡个体化目标AUC/最低抑菌浓度(MIC)比值为400~600 mg/(h·L)。由此可见目前就万古霉素临床监测指标存在争议。因此,本文就万古霉素治疗重症感染过程中进行治疗浓度监测的手段及策略进行综述,对指导临床合理用药具有重要意义,有助于临床医师制定个体化给药方案,最大程度减少或避免药物毒性。

感冒清热片防治甲型H1N1流感病毒感染的药效学研究

目的探讨感冒清热片防治甲型H1N1流感病毒感染的药效学情况。方法108例甲型H1N1流感病毒感染患者,随机分为观察组和对照组,每组54例。对照组使用磷酸奥司他韦治疗,观察组在对照组治疗基础上使用感冒清热片治疗。比较两组患者临床疗效、症状改善指标(起效时间、退热时间、止咳时间、痊愈时间)、以及治疗前后的中医证候(发热、咽痛、头痛、鼻塞流涕、咳嗽、乏力)积分、血清炎性因子[C反应蛋白(CRP)、肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)]。结果观察组治疗总有效率96.30%高于对照组的77.78%(P<0.05)。治疗后,观察组患者发热、咽痛、头痛、鼻塞流涕、咳嗽、乏力评分分别为(0.83±0.24)、(1.12±0.30)、(1.07±0.29)、(1.03±0.32)、(1.05±0.33)、(1.09±0.28)分,均低于对照组的(1.46±0.37)、(2.31±0.58)、(2.14±0.52)、(2.25±0.63)、(2.36±0.61)、(2.42±0.65)分(P<0.05)。观察组起效时间(1.03±0.34)d、退热时间(1.56±0.40)d、止咳时间(4.35±0.68)d、痊愈时间(6.63±1.26)d均短于对照组的(2.32±0.57)、(2.63±0.74)、(7.24±1.16)、(9.38±1.72)d(P<0.05)。治疗后,观察组CRP(2.11±0.56)mg/L、TNF-α(19.34±2.20)μg/L、IL-6(4.02±0.54)ng/L均低于对照组的(4.83±0.69)mg/L、(25.89±2.73)μg/L、(6.13±0.62)ng/L(P<0.05)。结论感冒清热片防治甲型H1N1流感病毒感染的疗效显著,能有效缓解证候,加快症状缓解速度,提高抗炎作用。

合欢花药效物质基础的研究进展

合欢花为豆科植物合欢(Albizia julibrissin Durazz.)的干燥花序或花蕾。具有解郁安神的功效,是中药“安神”作用最具代表性的花类药材,用于养心安神等。配伍的经典药对、方剂被广泛应用于治疗肝气郁滞、心神失养导致的抑郁症、焦虑症、睡眠障碍等精神相关疾病。本文通过对合欢花化学成分、药理作用、本草中的临床应用、药效物质基础的研究进行总结归纳,以期为合欢花的资源利用及新药开发提供参考。

脑梗死患者行经颅多普勒超声(TCD)与颈部血管超声(CUS)联合诊断效果分析

对脑梗死患者予以领出啊来检查,分析经颅多普勒超声与颈部血管超声联合诊断结果。方法 本次研究对收入的脑梗死患者、同期接受医院检查的健康体检对象予以诊断对比,均接受经颅多普勒超声与颈部血管超声检查,对比诊断结果。结果 对比诊断结果:经颅多普勒超声、联合检查、金标准检查的血管狭窄检出率差异不大,分别和金标准检查对比,(p>0.05),无统计学意义。结论 经颅多普勒超声检查和颈部血管超声联合检查方式可帮助脑梗死患者及时诊断出疾病,临床的误诊率、漏诊率较低,联合检查和金标准检查结果差异不大,(p<0.05),有统计学意义。

艾司氯胺酮和丙泊酚在宫腔镜手术中的药效学相互作用

目的采用响应曲面法分析艾司氯胺酮和丙泊酚在宫腔镜手术中的药效学相互作用。方法选择择期行宫腔镜手术患者45例,年龄18~64岁,BMI 18.5~28.0 kg/m^(2),ASAⅠ或Ⅱ级。选择不同血浆药物浓度的艾司氯胺酮(0、0.1、0.2、0.3、0.4、0.5、0.6、0.7、0.8μg/ml)复合丙泊酚靶控输注,术中维持艾司氯胺酮的血浆药物浓度不变,阶梯式增加丙泊酚的血浆药物浓度。评估扩张宫颈引起的体动反应。采用响应曲面模型分析艾司氯胺酮与丙泊酚的药效学相互作用。结果艾司氯胺酮(0~0.8μg/ml)与丙泊酚(1.0~7.0μg/ml)相互作用的三维响应曲面显示,两者抑制扩张宫颈引起的体动反应方面具有相加作用。抑制扩张宫颈引起的体动反应的艾司氯胺酮半数有效浓度(EC_(50))为0.61μg/ml(95%CI 0.41~0.81μg/ml),丙泊酚EC_(50)为4.69μg/ml(95%CI 3.17~6.21μg/ml)。结论响应曲面法可以定性和定量地分析艾司氯胺酮和丙泊酚的药效学相互作用规律,在抑制扩张宫颈引起的体动反应上,艾司氯胺酮和丙泊酚具有相加作用。

以药动学/药效学模型为基础的多种比阿培南 给药方案对于重症感染性疾病的抗菌效果

目的以药动学/药效学(PK/PD)模型为基础,采用蒙特卡洛模拟,针对重症感染患者的个体差异,设计比阿培南个性化用药方案以改善临床效果。方法收集重症患者比阿培南药动学参数,以常见致病菌大肠埃希菌、肺炎克雷伯菌、铜绿假单胞菌、鲍曼不动杆菌、金黄色葡萄球菌为目标菌株,引用中国细菌耐药监测研究报告中比阿培南对常见细菌最低抑菌浓度(MIC)值分布,通过调整给药剂量、给药间隔、滴注时间等方法制订不同给药方案,应用蒙特卡洛模拟计算各目标菌株不同给药方案的药效学获得概率(PTA)和累积反应分数(CFR),评估各给药方案治疗重症感染的抗菌效果。结果当MIC<0.125 mg/L时,比阿培南对5种目标菌株所有给药方案PTA值均>90%;当MIC≥4 mg/L时,所有给药方案PTA值均<90%;比阿培南对大肠埃希杆菌所有治疗方案CFR值均>90%,对鲍曼不动杆菌CFR值均<30%。结论比阿培南对大肠埃希菌的治疗可采用传统给药方案;对肺炎克雷伯菌的治疗可选择600 mg q6 h延时滴注3 h为最佳治疗方案,或根据MIC值优化给药方案;对于鲍曼不动杆菌、铜绿假单胞菌及金黄色葡萄球菌,应考虑换用或联用其他抗菌药物以达到疗效。

加味寿胎贴脐片释药动力学与药效学研究

本研究旨在通过体外透皮试验考察加味寿胎贴脐片的透皮效果,以大鼠先兆性流产模型的流产率、脏器指数、胚胎个数和血清激素水平为评价指标,进一步确定其疗效,以期为临床治疗先兆性流产提供疗效显著且使用方便的新制剂。试验采用Franz扩散池法进行体外透皮试验,考察贴脐片中金丝桃苷、槲皮素、大黄素和川续断皂苷Ⅵ的透皮吸收情况,以评价经皮渗透效果。建立大鼠先兆性流产模型,动物随机分为4组,即空白组、空白贴脐片对照组(只含辅料,不含药)、阳性组及加味寿胎贴脐片组,以流产率、脏器指数、胚胎个数、雌二醇(E2)、孕酮(P)、人绒毛膜促性腺激素(β-HCG)、前列腺素(PGF-2α)水平考察加味寿胎贴脐片对模型动物先兆性流产的影响。结果表明,加味寿胎贴脐片中4种指标成分24h累计透过量为142.68μg/cm^(2)、3.44μg/cm^(2)、3.78μg/cm^(2)、718.77μg/cm^(2),累计透过速率分别为0.0497μg/(cm^(2)·h)、0.0485μg/(cm^(2)·h)、0.0544μg/(cm^(2)·h)、0.045μg/(cm^(2)·h)。4种指标成分的透过率规律均符合一级动力学方程。金丝桃苷透过百分率为23.9%、槲皮素透过百分率为17.6%、大黄素透过百分率为27.7%、川续断皂苷Ⅵ透过百分率为27.1%。药效学试验结果显示,与空白贴脐片对照组相比,各给药组大鼠血清中E2、P、β-HCG的含量均有上调,PGF-2α的含量均有下调,贴脐片组在治疗先兆流产的作用上疗效显著,保胎效果更优。加味寿胎贴脐片具有体外经皮渗透的特性,对大鼠先兆性流产的治疗具有一定的改善作用,说明该制剂具有一定的临床开发价值。