Objective: Dasatinib and quercetin (D & Q) have demonstrated promise in improving aged-related pathophysiological dysfunctions in humans and mice. Herein we aimed to ascertain whether the heat stress (HS)-induced cognitive deficits in aged or even young adult male mice can be reduced by D & Q therapy. Methods: Before the onset of HS, animals were pre-treated with D & Q or placebo for 3 consecutive days every 2 weeks over a 10-week period. Cognitive function, intestinal barrier permeability, and blood-brain barrier permeability were assessed. Results: Compared to the non-HS young adult male mice, the HS young adult male mice or the aged male mice had significantly lesser extents of the exacerbated stress reactions, intestinal barrier disruption, endotoxemia, systemic inflammation and oxidative stress, blood-brain barrier disruption, hippocampal inflammation and oxidative stress, and cognitive deficits evaluated at 7 days post-HS. All the cognitive deficits and other syndromes that occurred in young adult HS mice or in aged HS mice were significantly attenuated by D & Q therapy (P < 0.01). Compared to the young adult HS mice, the aged HS mice had significantly (P < 0.01) higher severity of cognitive deficits and other related syndromes. Conclusions: First, our data show that aged male mice are more vulnerable to HS-induced cognitive deficits than those of the young adult male mice. Second, we demonstrate that a combination of D and Q therapy attenuates cognitive deficits in heat stressed aged or young adult male mice via broad normalization of the brain-gutendotoxin axis function.

Background: 7,8-Dihydroxyflavone (DHF) mimicks the physiological action of brain-derived neurotrophic factor (BDNF). Since local BDNF delivery to the injured spinal cord enhanced diaphragmatic respiratory function, we aimed to ascertain whether DHF might have similar beneficial effects after Brown-Sequard Syndrome in a rat model of spinal cord lateral hemisection (HX) at the 9th thoracic (T9) vertebral level. Methods: Three sets of adult female rats were included: sham+vehicle group, T9HX+vehicle group and T9HX+DHF group. On the day of surgery, HX+DHF group received DHF (5 mg/kg) while HX+vehicle group received vehicle. Neurobehavioral function, morphology of motor neurons innervating the tibialis anterior muscle and the transmission in descending motor pathways were evaluated. Results: Adult female rats received T9 HX had paralysis and loss of proprioception on the same side as the injury and loss of pain and temperature on the opposite side. We found that, in this model of Brown-Sequard syndrome, reduced cord dendritic arbor complexity, reduced cord motoneuron numbers, enlarged cord lesion volumes, reduced motor evoked potentials, and cord astrogliosis and microgliosis were noted after T9HX. All of the above -mentioned disorders showed recovery by Day 28 after surgery. Therapy with DHF significantly accelerated the electrophysiological, histological and functional recovery in these T9HX animals. Conclusions: Our data provide a biological basis for DHF as a neurotherapeutic agent to improve recovery after a Brown-Sequard syndrome. Such an effect may be mediated by synaptic plasticity and glia-mediated inflammation in the spared lumbar motoneuron pools to a T9HX.

Our initial studies detected elevated levels of 3,4-dihydroxyphenyllactic acid (DHPLA) in urine samples of patients with severe heart disease when compared with healthy subjects. Given the reported anti-inflammatory properties of DHPLA and related dihydroxylated phenolic acids (DPAs), we embarked on an exploratory multi-centre investigation in patients with no urinary tract infections to establish the possible pathophysiological significance and therapeutic implications of these findings. Chinese and Caucasian patients being treated for severe heart disease or those conditions associated with inflammation (WBC ≥ 10 ×109/L or hsCRP ≥ 3.0 mg/L) and/or hypoxia (PaO2 ≤ 75 mmHg) were enrolled; their urine samples were analyzed by HPLC, HPLC-MS, GC-MS and biotransformation assays. DHPLA was detected in urine samples of patients, but undetectable in healthy volunteers. Dynamic monitoring of inpatients undergoing treatment showed their DHPLA levels declined in proportion to their clinical improvement. In DHPLA-positive patients' fecal samples, Proteus vulgaris and P. mirabilis were more abundant than healthy volunteers. In culture, these gut bacteria were capable of reversible interconversion between DOPA and DHPLA. Furthermore, porcine and rodent organs were able to metabolize DOPA to DHPLA and related phenolic acids. The elevated levels of DHPLA in these patients suggest bioactive DPAs are generated de novo as part of a human's defense mechanism against disease. Because DHPLA isolated from Radix Salvia miltiorrhizae has a multitude of pharmacological activities, these data underpin the scientific basis of this medicinal plant's ethnopharmacological applications as well as highlighting the therapeutic potential of endogenous, natural or synthetic DPAs and their derivatives in humans.

ObjectiveThis article reviewed research conducted on economic evaluations of clinical pharmacy services (CPS) in China. We aimed to identify the types of CPS and the possible economic effects of these services and to hopefully provide some suggestions for designing future economic evaluations of pharmacy interventions in the region.DesignSystematic review.Data sourcesSeveral English databases (PubMed, Embase, The Cochrane Library, National Health Service Economic Evaluation Database), Chinese databases (China National Knowledge Infrastructure, VIP, Chinese Biomedical Literature Database and WanFang Data) and search engines (Google Scholar and BaiDu Scholar) were searched through December 2017.Eligibility criteria for selecting studiesStudies with an economic assessment of CPSs in China were included.Data extraction and synthesisTwo reviewers independently screened the studies, extracted the data, assessed the quality of the included studies and then qualitatively analysed the results.ResultsForty articles were included in the final analysis. Most studies were performed in hospitals and the intervention populations mainly included adults. The types of pharmaceutical services included antimicrobial management, chronic disease state management and multidimensional clinical pharmaceutical services. A positive economic benefit associated with CPS was noted in 80% (n=32) of these articles, showing that CPS were associated with cost savings and improved patient outcomes. However, only three studies were full economic evaluations, using the method of cost-effectiveness analysis.ConclusionCPS was associated with cost savings and generated positive economic value. With the expanding role of pharmacists in the healthcare sector, it is suggested that new pharmaceutical services be used in future studies and that high-quality full economic evaluations capturing both expenses and cost savings be conducted.

目的 建立同时测定血浆中丹参素(DSS)、原儿茶酸(PA)及羟基红花黄色素A(HSYA)的HPLC分析方法,研究丹红注射液主要酚酸类成分DSS、PA以及HSYA在正常和寒凝血瘀大鼠中药代动力学行为.方法 正常及寒凝血瘀模型大鼠各6只,尾静脉注射丹红注射液.采用HPLC法检测给药后2、5、10、15、20、25、30、40、50、60、90 min时血浆中DSS、PA以及HSYA的浓度,流动相为0.2％甲酸水(A)_甲醇(B),梯度洗脱,梯度波长检测:280 nm(0～40 min),402 nm(40～60min).DAS 3.0软件计算药代动力学参数.结果 DSS和PA呈现二室开放模型,HSYA呈现三室模型.与正常组相比,模型大鼠体内DSS、PA和HSYA的达峰浓度Cmax、DSS的分布半衰期t1/2α、PA和HSYA的消除半衰期t12α(t12γ)和药时曲线下面积AUC以及总表观分布容积V均增大(P＜0.05);PA和HSYA的分布半衰期t1/2α和DSS药时曲线下面积AUC均降低(P＜0.05).结论 在寒凝血瘀病理模型下,DSS在体内分布减慢,生物利用度降低;PA和HSYA的分布加快,消除减慢,表观分布容积增大,生物利用度增加,更能发挥好疗效.

Objective To optimize the extraction procedure of the couple herbs,Radix paeoniae Alba and Rhizoma chuanxiong.Methods Orthogonal design was employed to optimize the extracting procedure.The content of three ingredients(gallic acid,paeoniflorin,ferulic acid) were used as index,the concentration of alcohol,the amount of alcohol,the extraction time,and the number of extraction times were used to study the effect on the content.Results The optimial preparation conditions were as follows:adding 12 times 50% alcohol,reflowing extraction 2 times,2 hours each time.Conclusion The established method was stable and feasible,and thus could provide a theoretical basis for the further research of the couple herbs.

OBJECTIVE:To investigate the pharmacokinetic effect of Sappan Lignum on hydroxysafflor yellow A (HSYA) in Carthami Flos.METHOD:Concentration of HSYA in rat plasma was detected by RP-HPLC after rats were orally administered with extracts of Carthami Flos or Carthami Flos combined with Sappan Lignum. Pharmacokinetic parameters were calculated by DAS 2.0 pharmacokinetic software.RESULT:In vivo pharmacokinetic models of HSYA were two-compartment open models in both of the Carthami Flos group and the Carthami Flos combined with Sappan Lignum group. After compatibility, HSYA showed a significant lower in apparent volumes of distribution of t(1/2Ka), t(1/2alpha) and V1/F, with slight advance in T(max).CONCLUSION:Sappan Lignum can accelerate absorption, distribution and metabolic process of HSYA in vivo and reduce its accumulation in vivo.

目的 建立红花水提物中有效成分群的定性分析方法.方法 采用加热回流法获得红花的水溶性总提物,以槲皮素和羟基红花黄色素A为指标进行方法学考察,用高效液相色谱-二极管阵列-离子阱质谱(HPLC-DAD-MSn)法定性分析红花水提物中的有效成分群.结果 红花水提物中槲皮素和羟基红花黄色素A含量分别为0.13%和1.14%,定性分析了红花水提物中19种化学成分,其中1种为未知化学成分.结论 所用方法专属性强,可作为红花水提物中有效成分群的定性分析方法.