Simultaneous Determination of Six Compounds in Rat Plasma by Ultra‑Performance Liquid Chromatography with Tandem Mass Spectrometry: Application in the Pharmacokinetic Study of Qing Gan‑Shu Yu‑Fang

A rapid and high selective ultra?performance liquid chromatography (UPLC) with tandem mass spectrometry method for simultaneous determination of six compounds including albiflorin, paeoniflorin, picroside I, picroside II, saikosaponin A, and saikosaponin D in rat plasma was developed and validated using butyl p-hydroxybenzoate as an internal standard. One-step direct protein precipitation with acetonitrile was used to extract the compounds from the rat plasma samples. Chromatographic separation was achieved using an ACQUITY UPLC BEH C18 column (100 mm × 2.1 mm, 1.7 µm) at a flow rate of 0.4 mL/min, using gradient mode containing 0.1% formic acid in water and acetonitrile were used as the Mobile phase A and B. Electrospray ionization in negative ion mode and multiple reaction monitoring were used to identify and quantify active components. Calibration curves showed good linearity (R2 > 0.9908) over a wide concentration range for all compounds. The intra- and interday precision (relative standard deviation) ranged 2.4%–7.0% and 2.6%–8.0%, respectively. The accuracy (relative error) was from ?13.0% to 13.2% at all quality control levels. The recovery ranged from 81.1% to 92.5%. The validated method was successfully applied to pharmacokinetic study in rats after oral administration of Qing Gan?Shu Yu?Fang. The results show that one can draw a conclusion that these six active ingredients can be quickly absorbed and play a pharmacodynamic role rapidly in vivo.     

Dose optimization of intrathecal administration of human umbilical cord mesenchymal stem cells for the treatment of subacute incomplete spinal cord injury

Human umbilical cord mesenchymal stem cells(hUC-MSCs)are a promising candidate for spinal cord injury(SCI)repair owing to their advantages of low immunogenicity and easy accessibility over other MSC sources.However,modest clinical efficacy hampered the progression of these cells to clinical translation.This discrepancy may be due to many variables,such as cell source,timing of implantation,route of administration,and relevant efficacious cell dose,which are critical factors that affect the efficacy of treatment of patients with SCI.Previously,we have evaluated the safety and efficacy of 4×10⁶ hUC-MSCs/kg in the treatment of subacute SCI by intrathecal implantation in rat models.To search for a more accurate dose range for clinical translation,we compared the effects of three different doses of hUC-MSCs-low(0.25×10⁶ cells/kg),medium(1×10⁶ cells/kg)and high(4×10⁶ cells/kg)-on subacute SCI repair through an elaborate combination of behavioral analyses,anatomical analyses,magnetic resonance imaging-diffusion tensor imaging(MRI-DTI),biotinylated dextran amine(BDA)tracing,electrophysiology,and quantification of mRNA levels of ion channels and neurotransmitter receptors.Our study demonstrated that the medium dose,but not the low dose,is as efficient as the high dose in producing the desired therapeutic outcomes.Furthermore,partial restoration of theγ-aminobutyric acid type A(GABAA)receptor expression by the effective doses indicates that GABAA receptors are possible candidates for therapeutic targeting of dormant relay pathways in injured spinal cord.Overall,this study revealed that intrathecal implantation of 1×10⁶ hUC-MSCs/kg is an alternative approach for treating subacute SCI.     

Inhibition of focal adhesion kinase enhances antitumor response of radiation therapy in pancreatic cancer through CD8+ T cells

Objective:Pancreatic ductal adenocarcinoma(PDAC)is a deadly malignancy,due in large part to its resistance to conventional therapies,including radiotherapy(RT).Despite RT exerting a modest antitumor response,it has also been shown to promote an immunosuppressive tumor microenvironment.Previous studies demonstrated that focal adhesion kinase inhibitors(FAKi)in clinical development inhibit the infiltration of suppressive myeloid cells and T regulatory(T regs)cells,and subsequently enhance effector T cell infiltration.FAK inhibitors in clinical development have not been investigated in combination with RT in preclinical murine models or clinical studies.Thus,we investigated the impact of FAK inhibition on RT,its potential as an RT sensitizer and immunomodulator in a murine model of PDAC.Methods:We used a syngeneic orthotopic murine model to study the effect of FAKi on hypofractionated RT.Results:In this study we showed that IN10018,a small molecular FAKi,enhanced antitumor response to RT.Antitumor activity of the combination of FAKi and RT is T cell dependent.FAKi in combination with RT enhanced CD8+T cell infiltration significantly in comparison to the radiation or FAKi treatment alone(P<0.05).FAKi in combination with radiation inhibited the infiltration of granulocytes but enhanced the infiltration of macrophages and T regs in comparison with the radiation or FAKi treatment alone(P<0.01).Conclusions:These results support the clinical development of FAKi as a radiosensitizer for PDAC and combining FAKi with RT to prime the tumor microenvironment of PDAC for immunotherapy.     

心房颤动的导管消融治疗

心房颤动(简称“房颤”)是心血管疾病中无论在控制症状方面还是改善预后方面均不理想的病种。房颤的导管消融作为一种新的治疗手段,从10年前诞生之日起就引发了房颤治疗的革命,近2年来,越来越多的国内外医学中心已将其作为房颤的常规治疗。本文就现阶段如何选择房颤导管消融治疗的适应证作简要评价。1目前的方法简介由于迄今的资料充分证实房颤的起源90%以上位于肺静脉及其与左房后壁的过渡区域(肺静脉前庭),导管根治房颤的方法也就集中在将该区域与左房之间的电学传导阻断。目前的主流方法是在三维标测系统CARTO或NavX指导下行肺静脉隔…     

交通伤中腹部闭合性损伤合并颅脑伤的早期诊治

在所有致伤原因中．道路交通伤（road traffic injury，RTI）占50％左右．我国交通伤人数呈不断增多趋势。在RTI患者死亡的危险因素中。内脏损伤与颅脑损伤均为主要致死因素口，两者并存给救治带来更大挑战。多发伤患者死亡高峰在伤后68小时以内．约占80％。因此，如何早期诊治．以提高治愈率、减少并发症、降低死亡率有着非常重要的意义。总结如下。     

磷酸化信号传导与转录激活因子3在前列腺癌早期诊断中的应用

目的 探讨前列腺穿刺标本中磷酸化信号传导与转录激活因子3(P-STAT3)表达在前列腺癌(PCa)早期诊断中的应用价值.方法采用免疫组织化学方法检测接受重复穿刺的PCa患者初次穿刺未检出癌的标本(29例)、重复穿刺确诊PCa时的癌灶标本(29例)、重复穿刺确诊PCa时的非癌灶标本(29例)以及良性前列腺增生(BPH)患者初次穿刺标本(29例)中P-STAT3的表达.统计学分析其与临床诊断的相关性及对PCa发生的预测作用.结果 P-STAT3在PCa患者癌灶标本、非癌灶标本及初次穿刺标本中阳性表达率分别为93.1%(27/29)、82.8%(24/29)和86.2%(25/29),在BPH标本中阳性表达率为10.3%(3/29),前三者的阳性率明显高于后者(X2=60.123,P=0.000);如以初次穿刺标本中P-STAT3表达阳性作为PCa的诊断标准,该方法的敏感性为86.2%,特异性为89.7%.结论 检测穿刺标本P-STAT3表达可以作为前列腺穿刺活检的辅助诊断方法,用于PCa的早期诊断,预测PCa的发生.     

亚低温治疗颅脑损伤延长翻身间隔时间与压疮关系的研究

[目的]探讨颅脑损伤病人应用亚低温治疗仪时具体间隔多长时间翻身不发生压疮.[方法]随机选择45例颅脑损伤应用亚低温治疗的病人,采取3 h后开始翻身,侧卧位时每次均为1 h,以后平卧位时间每次逐渐递增1/2 h.[结果]在应用亚低温治疗期间除3例病人在不同时段内发生轻微紫色冻伤外,所有病例均未发生压疮,平均翻身间隔时间为11.31 h,应用单样本统计学处理,有统计学意义(t=8.867,P<0.005).[结论]颅脑损伤病人在使用亚低温治疗过程中翻身间隔时间可以延长至8 h不发生压疮.     

THE BASIC CHARACTERISTICS OF THE NUCLEOTIDE SEQUENCE OF 5S RIBOSOMAL RNA FROM THE HUMAN WORM PARASITE FASCIOLOPSIS BUSKI

With the method of rapid gel sequencing, the complete nueleotide sequence of Fasciolopsis buski 5S rRNA has been determined: AAC GGG AUG AAG CUA GAC AUG UGG CGG CCU AGU UGG AGG UCG GAA CUC GGA AGU UAA GGA AUG UUG GGC CUG GUU AGU ACU GGU AUG GGU GAC CUU GGG AAU ACC GGG UGU UGC GUC CA_(OH) This have been compared with 553 species of other organisms 5S rRNA sequences previously published and fitted to a secondary structural model.     

Influence of Qingdai Compound Capsule on the expression of c-myc in psoriatic keratinocytes) on the expression of c-myc in psoriatic keratinocytes

In this immunohistochemical study, the authors detected the expression of c-myc in keratinocytes (ECK) from 30 psoriatics before and after Qingdai Compound Capsule (QDCC) treatment and 12 normal subjects for control. The results showed that the ECK of patients before treatment was significantly higher than that in the normal control group, and its level was correlated with histopathological changes of affected skin. After treatment the ECK was normalized. It is believed that QDCC could decrease the ECK in psoriatics and this effect was probably mediated by inhibiting c-myc expression. This study provided an experimental evidence for the application of QDCC in treating psoriasis.