The developments of silicosis drugs / 药学学报

Pneumoconiosis is the most common occupational disease in China, which severely endangers people's health. Depending on the inhaled air pollutants, pneumoconiosis is classified as anthracosis, silicosis, asbestosis, etc., among which silicosis is the most common and serious. Silicosis is a systemic, poor prognostic disease characterized by diffuse fibrosis of lung tissue, which is caused by long-term exposure to dust with high levels of free silicon dioxide (SiO2) in the occupational environment. Appropriate treatment in time is important for the disease. Unfortunately, no effective drugs have been approved to delay or even reverse pulmonary fibrosis caused by SiO2. This review briefly classifies potent therapeutic drugs and compounds in term of mechanisms, providing the probability for clinical treatment of silicosis.

The biological principle of "Biao Ben Jian Zhi" / 药学学报

Along with the progress of pharmaceutical science in the past century, the theme of pharmacology has gone through pseudo agent scheme, to ligand-receptor model, and then to the theory of targeted therapy today. Due to the success of drug R&D, current drug research keeps its focus mainly on drugs with single target and precise treatment, in which the molecular mechanism is relatively clear but the therapeutic efficacy is often limited. Thus, there is a big space for exploration in the field of pharmacology. In the past 30 years, several novel chemical drugs, originated from traditional Chinese medicine, have been identified and then used in clinic, provoking a strong interest to explore new theory for pharmacology, of which the term of "Biao Ben Jian Zhi" (treating diseases by directing symptoms and root causes) has demonstrated a promising nature. We consider this concept useful for future drug discovery, drug design and clinical therapy. In this review, example drugs such as berberine, metformin and azvudine, are discussed, and "drug Cloud" (dCloud) model is introduced to elaborate the mechanism of treating diseases by directing symptoms and root causes of diseases.

Short chain fatty acid: a messenger of gut-organ axis for disease regulation / 药学学报

Gut microbiota is a complex and dynamic system, and is essential for the health of the body. As the "second genome" of the body, it can establish communication with the important organs by regulating intestinal nerves, gastrointestinal hormones, intestinal barrier, immunity and metabolism, thus affecting host′s physiological functions. Short chain fatty acid (SCFA), known as one important metabolite of intestinal microbiota, is regarded as a significant messenger of the gut-organ communication, due to its extensive regulation in the body′s immunity, metabolism, endocrine and signal transduction. In this review, we summarize the interaction between gut-liver/brain/kidney/lung axis and diseases, and focus on the role and mechanism of SCFA in the gut-organ communication, hoping to provide new ideas for the treatment of the related diseases.

Dengzhan Shengmai inhibits nonalcoholic fatty liver disease via regulating intestinal microenvironment / 药学学报

The aim of this study was to investigate the efficacy and mechanism of Dengzhan Shengmai (DZSM) against nonalcoholic fatty liver diseases (NAFLD). The animal experiment program was reviewed and approved by the Ethics Committee of Institute of Materia Medica, Chinese Academy of Medical Sciences. The NAFLD model of Syrian golden hamsters was established by high fat diets. After 6 weeks of DZSM treatment, the serum lipid, hepatic lipid accumulation, liver function and inflammatory response were determined. The regulations of gut microbiota and short-chain fatty acids were detected by 16S rRNA gene sequencing and gas chromatography-mass spectrometry method, respectively. The gut barrier function was evaluated by enzyme linked immunosorbent assay (ELISA), reverse transcription-quantitative polymerase chain reaction (RT-qPCR), Western blot and histopathological methods and further verified in HepG2 cells. The results showed that the efficacy of DZSM against NAFLD was remarkably reduced after removal of the gut microbiota. The study of mechanism showed that DZSM significantly regulated the composition of gut microbiota, promoted the production and absorption of intestinal short-chain fatty acids, then leading to the reduction of hepatic lipid accumulation. Moreover, after DZSM treatment, the decreased lipopolysaccharide (LPS) level by improving the intestinal barrier function significantly inhibited the hepatic inflammation through down-regulating Toll like receptor 4 (TLR4)-nuclear factor kappa B (NFKB) signaling pathway. These results indicate that DZSM inhibits NAFLD via regulating intestinal microenvironment.

Chlorogenic acid down-regulates the expression of PD-L1 in esophageal squamous cell carcinoma via IFN-γ signaling pathway / 药学学报

In this study, the regulatory effects of chlorogenic acid (CGA) on the expression of programmed cell death ligand 1 (PD-L1) in esophageal squamous cell carcinoma (ESCC), as well as the role of interferon γ (IFN-γ), has been discussed using both in vitro and in vivo animal models. ESCC murine model was established according to the standard operating procedures (SOP) of Animal Experiment Center of Institute of Materia Medica, Chinese Academy of Medical Sciences. The expression of PD-L1 in esophageal tissues of murine models was analyzed using the microarray assay. Then, the results were verified by qRT-PCR, Western blot and immunohistochemistry (IHC) staining, the molecular mechanism was explored in KYSE180 and KYSE510 ESCC cells in vitro. The results showed that CGA could suppress the expression of PD-L1 in tumor tissues in murine models significantly, rather than the expression in KYSE180 and KYSE510 ESCC cells in vitro. However, after the pretreatment of IFN-γ, the expression of PD-L1 was significantly increased, then it was down-regulated by CGA in both dose- and time-dependent manner. Meanwhile, the expression of interferon regulatory factor 1 (IRF1), an upstream regulatory factor of PD-L1, was suppressed by CGA in both KYSE180 and KYSE510 pretreated with IFN-γ, which was consistent with the expression of PD-L1. These results indicate that CGA down-regulates the expression of PD-L1 in ESCC via IFN-γ-IRF1 signaling pathway, providing the molecular theoretical basis for exploration of new treatment of ESCC.

Comparison of planting modes of Dendrobium huoshanense and analysis of advantages of simulated cultivation / 中国中药杂志

Dendrobium huoshanense is a precious medicinal plant belonging to Dendrobium of Orchidaceae. It is a special medicinal material and extremely scarce in Huoshan county, Anhui province. At present, D. huoshanense has been greatly protected, which also makes it possible to industrialize relying on tissue culture and artificial cultivation technology. Three main planting methods were utilized for cultivating D. huoshanense including facility cultivation, under forest cultivation and simulative habitat cultivation. Firstly, the three cultivation modes and technical characteristics of D. huoshanense were compared and analyzed, and it was found that the ecological environment of D. huoshanense cultivated in the simulated environment was closer to that of wild D. huoshanense. Secondly, based on comparing the characters and quality of three cultivation modes, the results showed that the shape of D. huoshanense cultivated in simulated environment was more similar to that of "grasshopper thigh" recorded in Bencao Jing Jizhu, and its quality was better than that of facilities and under forest cultivation. The comprehensive benefit comparison of three modes showed that the simulated cultivation had high income, the lowest input-output ratio and significant economic benefit. The quality of cultivated D. huoshanense was further evaluated from four aspects of "excellent environment" "excellent shape" "high quality" "excellent effect", which summarized the comprehensive advantages of simulative habitat cultivation of D. huoshanense as follows: the original habitat and site environment of simulated wild D. huoshanense, the closer shape to the wild, the more content of main medicinal components, and higher economic benefit and better efficacy. The quality of D. huoshanense was improved by the use of simulative habitat cultivation, which has practical significance to guide its large-scale cultivation.

Ecological agriculture of Chinese materia medica:update and future perspectives / 中国中药杂志

This study steps through four key principles, four open problems and future perspectives of Chinese materia medica(CMM) ecological agriculture by presenting the historical development, existing theories and practice outcomes. Then, it focuses on refining the main principles of CMM ecological agriculture:(1)the principles of ecological niche associated with yield and comprehensive income;(2)principles of biological diversity associated with the integrated control of diseases, pests and weeds;(3)principles of adversity effects associated with the quality improvement of CMM;(4)principles of structural stability associated with the sustainable development of CMM ecological agriculture. On this basis, four burning issues of CMM ecological agriculture were obtained,(1)ecological planting mode and supporting technologies need to be perfect;(2)multi-integrated industrial coupling remains to strengthen;(3) quality assurance system of CMM ecological agriculture and high-quality and favorable price model remains to be formed;(4)awareness of the demonstration and extension of CMM ecological agriculture needs to be desired. Finally, suggestions for the sustainable development of CMM ecological agriculture are put forward:(1)strengthen the national planning and layout, develop CMM ecological agriculture accor-ding to local conditions;(2)pay equal attention to inheritance and innovation, and strengthen the theory and practical technology research of CMM ecological agriculture;(3)strengthen industrial coupling and realize the transformation of CMM ecological agriculture from a production-based to a multi-in-one compound model;(4)intensify standards and brands, building a quality assurance system for CMM ecological products;(5) publicize the demonstration and popularization of CMM ecological agriculture. In summary, the development of CMM ecological agriculture possessed a firmer theory and practice foundation, although there is still much room for improvement. A better field of Chinese medicine agricultural development with immense economic and social benefits will not a question of "if" but "when" by accurately grasp the way forward.

Comparison of active ingredients and protective effects of Dendrobium huoshanense of different growth years on acute liver injury / 中国中药杂志

The differences of the active ingredients in Dendrobium huoshanense of different growth years and their protective effects on acute liver injury were studied to provide evidence for optimizing harvest time. The contents of polysaccharides, total flavonoids and total alkaloids in D. huoshanense of different growth years were determined by UV spectrophotometry, and the contents of gigantol in D. huoshanense were determined by HPLC. C57 BL/6 mice were randomly divided into blank control group(saline), modeling group(saline), high-dose(7.5 g·kg~(-1)) and low-dose(1.25 g·kg~(-1)) groups of D. huoshanense of different growth years. Each group was intragastrically administered every day for 2 weeks. 500 mg·kg~(-1) paracetamol was injected intraperitoneally 2 h after last treatment except the control group. After 12 hours, the serum and liver tissues were collected to detect the activities of ALT and AST, and the levels of SOD and MDA. The hepatic histopathological examination was performed. The results showed that the chemical constituents of D. huo-shanense of different growth years were significantly different(P<0.05). The contents of polysaccharide and gigantol of D. huoshanense of 2 growth years were the highest. The contents of flavonoids and alkaloids of D. huoshanense of 3 growth years were the hig-hest, followed by the D. huoshanense of 2 growth years, and the lowest were that of 1 growth year. Compared with the modeling group, D. huoshanense of different growth years could decrease the activities of ALT and AST in serum. Meanwhile, the levels of MDA reduced significantly, while those of SOD increased markedly. Histopathological results suggested that all D. huoshanense samples were effective in the reduction of the necrosis of hepatocytes in different degrees. The results of the multi-component SPSS paired tests showed that polysaccharide and gigantol probably played a leading role in the liver protection effects, while D. huoshanense of 2 growth years showed the best efficacy. The optimal harvesting time of D. huoshanense is 2 growth years.

The anti-atherosclerotic effect and mechanism of puerarin / 药学学报

In recent years, with the improvement in living standards, the morbidity and mortality of cardiovascular and cerebrovascular diseases has increased markedly. Atherosclerosis is the main pathological basis for cardiovascular and cerebrovascular diseases, and there are many risk factors for atherosclerosis. The pharmacological effects of puerarin are broad, and considerable clinical data confirms that puerarin has a definite effect on cardiovascular diseases resulting from atherosclerosis. The use of puerarin for atherosclerosis has increased in recent years. This article reviews the effect and mechanism of puerarin on atherosclerosis.

Isolation of Fusarium and identification of its toxins from tuberous root of Pseudostellaria heterophylla / 中国中药杂志

Fusarium is the major pathogen of root rot of Pseudostellaria heterophylla. This study aims to explain the possible distribution of Fusarium species and the contamination of its toxin-chemotypes in tuberous root of P. heterophylla. A total of 89 strains of fungi were isolated from the tuberous root of P. heterophylla. Among them, 29 strains were identified as Fusarium by ITS2 sequence, accounting for 32.5%. They were identified as five species of F. avenaceum, F. tricinctum, F. fujikuroi, F. oxysporum, and F. graminearum based on β-Tubulin and EF-1α genes. LC-MS/MS detected 18, 1, and 5 strains able to produce ZEN, DON, and T2, which accounted for 62.1%, 3.4%, and 17.2%, respectively. Strain JK3-3 can produce ZEN, DON, and T2, while strains BH1-4-1, BH6-5, and BH16-2 can produce ZEN and T2. PCR detected six key synthase genes of Tri1, Tri7, Tri8, Tri13, PKS14, and PKS13 in strain JK3-3, which synthesized three toxins of ZEN, DON, and T2. Four key synthase genes of Tri8, Tri13, PKS14, and PKS13 were detected in strains BH1-4-1, BH6-5, and BH16-2, which were responsible for the synthesis of ZEN and T2. The results showed that the key genes of toxin biosynthesis were highly correlated with the toxins produced by Fusarium, and the biosynthesis of toxin was strictly controlled by the genetic information of the strain. This study provides a data basis for the targeted prevention and control of exo-genous mycotoxins in P. heterophylla and a possibility for the development of PCR for rapid detection of toxin contamination.

Strategies for medicinal plants adapting environmental stress and "simulative habitat cultivation" of Dao-di herbs / 中国中药杂志

This paper analyzed life form, habitats and environmental stresses of medicinal plants and algal fungi collected in Chinese Pharmacopoeia(2015). ①It was found that only 0.94% of the medicinal plants mainly cultivated in field. The most common habitats of medicinal plants are divided into two types: those whose natural habitats are forest margins/undergrowth(about 42.53%) and those whose natural habitats are roadside, hillside, wasteland/sand(about 43.78%). The former mainly faces environmental stresses such as weak light, pests and diseases; the latter often faces the main environmental stresses of drought, strong light, ultraviolet radiation, high temperature, low temperature(day and night or annual temperature difference is large), nutrient deficiency, pests and so on. ②Based on analyzing the strategies of medicinal plants to adapt to environmental stresses, it is pointed out that the synthesis and accumulation of secondary metabolites are the most important strategies of medicinal plants to protect against environmental stresses. In the process of long-term adaptation to specific stress, the accumulation of relevant genetic variation and epigenetic inheritance has become an important condition for the formation of quality of medicinal plants. ③It is proposed that "simulative habitat cultivation" has obvious advantages in balancing growth and secondary metabolism and guaranting the quality of traditional Chinese medicinal materials.

Effect of Oxymatrine on Oxidative Stress Injury of H9C2 Cells Induced by High Glucose / 中国实验方剂学杂志

Objective:To study the protective mechanism of oxymatrine on oxidative stress induced by high glucose in H9C2 cells. Method:H9C2 cardiomyocytes were cultured in groups and divided into normal group, high glucose (HG) group, low-dose oxymatrine (OMT) group (50 mg·L-1), high-dose OMT group (100 mg·L-1), positive drug vitamin E (VE) group (1×10-4 mol·L-1) and mannitol (M) wasotonic control group. Cell damage was detected by lactate dehydrogenase leakage, changes in cell superoxide dismutase (SOD) activity and malondialdehyde (MDA) content were detected, intracellular reactive oxygen species (ROS) content and cellular mitochondria and functional integrity were detected by fluorescent probes, and Western blotting was used to detect the expressions of Bcl family proteins. Result:Compared with the normal group, the content of malondialdehyde and reactive oxygen species and the expression level of pro-apoptotic protein in the high glucose group were significantly increased (P<0.01), while the activity of superoxide dismutase and the expression levels of mitochondrial membrane potential (MMP) and anti-apoptotic protein were significantly decreased (P<0.01). Compared with the high glucose group, oxymatrine significantly reduced the leakage of lactate dehydrogenase, significantly inhibited the production of intracellular ROS (P<0.01), reduced the amount of malondialdehyde and down-regulated the expression of pro-apoptotic protein (P<0.05), increased the activity of superoxide dismutase, regulated MMP and improved the expression of anti-apoptotic protein (P<0.01). Conclusion:Oxymatrine can regulate oxidative stress by improving mitochondrial function, so as to inhibit the apoptosis of H9C2 cardiomyocytes induced by high glucose.

Clinical Efficacy of Liuwei Dihuangwan Combined with Danzi Xiaoyaosan on H-type Hypertension with Syndrome of Yin Deficiency and Yang Hyperactivity / 中国实验方剂学杂志

Objective::To discuss the clinical efficacy of Liuwei Dihuangwan combined with Danzi Xiaoyaosan on H-type hypertension with syndrome of Yin deficiency and Yang hyperactivity and its effect on vascular endothelial function and inflammatory factors. Method::One hundred and fifty patients were randomly divided into control group (75 cases) and observation group (75 cases) by random number table.Patients in control group got enalapril maleate and folic acid tablets, 1 tablet/time, 1 time/day, and patients with uncontrollable blood pressure were also given nifedipine sustained-release tablets, 20-30 mg/time, 2 times/days.In addition of the therapy of control group, patients in observation group were also given modified Liuwei Dihuangwan combined with Danzi Xiaoyaosan, 1 dose/day.The course of treatment was 12 weeks.Before and after treatment, systolic blood pressure (SBP), diastolic blood pressure (DBP) and up-to-standard blood pressure were detected.And ambulatory blood pressure, standard deviation of 24-hours systolic blood pressure (24 h SSD), standard deviation of 24-hour diastolic blood pressure 24 h DSD), 24 h mean systolic blood pressure (24 h SBP), 24 h mean diastolic blood pressure (24 h DBP) were recorded.And ankle brachial index (ABI) and brachial artery blood flow mediated diamete (FMD) were discussed, syndrome of Yin deficiency and Yang hyperactivity was scored, and levels of iterleukin-6 (IL-6), IL-10, high-sensitivity C-reactive protein (hsCRP) and homocysteine (Hcy) were detected. Result::The levels of SBP, DBP, 24 h SSD, 24 h DSD, 24 h SBP and 24 h DBP were all lower than those in control group (P<0.01). The achievement rate of accidental blood pressure in observation group was 81.19%, which was higher than 66.98% in control group (χ2=29.81, P<0.01). And levels of ABI, FMD and IL-10 were higher than those in control group (P<0.01), while the score of syndrome of Yin Deficiency and Yang Hyperactivity and the levels of Hcy, leptin, IL-6 and hs-CRP were lower than those in control group (P<0.01). Conclusion::In addition to the therapy of antihypertensive and folic acid, Liuwei Dihuangwan combined with Danzi Xiaoyaosan can be given to control the level of blood pressure and Hcy, relieve the variability of blood pressure, alleviate clinical symptoms, raise the rate of achievement rate of blood pressure, improve the function of vascular endothelium, and regulate inflammatory factors.

Analysis of the metabolites of isoacteoside in rat urine by UHPLC-LTQ-Orbitrap / 国际中医中药杂志

Objective:To analyze the metabolites of isoacteoside in rat's urine after oral administration by UHPLC-LTQ-Orbitrap and then summarize its metabolic pathways.Methods:The rats were randomly divided into treatment and control groups. Isoacteoside dissolved in saline was orally administered to the rats in the treatment group witht a single dose of 100 mg/kg. At the same time, saline was orally administered to the control group with the same volume. The urine samples were collected for 12 h and then purified. Sample analyses were performed on a Thermo Scientific BOS Hypersil C18 column (2.1 mm × 150 mm, 2.4 μm), the mobile phase consisted of water containing 0.1% formic acid-acetonitrile in a gradient program, the flow rate was set at 0.3 ml/min and the column was maintained at 30 ℃. The urine samples of the treatment group and control groups were detected with negative ion mode.Results:The metabolites were identified according to their protonated molecular ions and fragment ions and by comparing the mass data with that of reference standards and the published data. In total, 8 metabolites of isoacteoside were detected and identified in the urine samples of treatment group and the major metabolic pathway of isoacteoside included glucuronide conjugation, dehydroxylation, hydrolyzation, methyl conjugation and sulphate conjugation.Conclusions:UHPLC-LTQ-Orbitrap could be used to analyze the main metabolites and metabolic pathways of isophylloside in rats, which can provide references for further studies on pharmacodynamics and pharmacological mechanisms.

Study on the mechanism of two related Chinese herbs Danggui-Baishao in treating cardiovascular diseases based on network pharmacology / 国际中医中药杂志

Objective:By adopting network pharmacology to study the mechanism of the two classical Chinese herbs Danggui-Baishao in treating cardiovascular diseases. Methods:By searching from TCMSP and related literature, together with the databases of TCMSP, SWISS and STITCH, potential active compounds of Danggui-Baishao were collected, while the targets for cardiovascular diseases were obtained from TTD, OMIM and DrugBank databases. Then the PPI network was screened for the major targets. The KEGG Pathway annotation analyses of major targets were performed by using the DAVID database. The ingredient-major target-key pathway network was constructed by Cytoscape. Results:There were 17 compounds and 54 major targets in the ingredient-target-pathway network, as well as 10 key pathways, including inflammation-related pathway (TNF signaling pathway), pathways related to cardiovascular system (such as PI3K-Akt signaling pathway, FoxO signaling pathway, VEGF signaling pathway, Rap1 signaling pathway), prolactin signaling pathway and estrogen signaling pathway.Conclusions:The study verified the characteristics of multi-components, multi-targets and integral regulation for Danggui-Baishao with the application of network pharmacology. It predicted that Dangui-Baishao couldtreat cardiovascular diseases mainly by regulating angiogenesis, inflammatory response and apoptosis.

Study on the mechanism of two related Chinese herbs Danggui-Baishao in treating cardiovascular diseases based on network pharmacology / 国际中医中药杂志

Objective@#By adopting network pharmacology to study the mechanism of the two classical Chinese herbs Danggui-Baishao in treating cardiovascular diseases.@*Methods@#By searching from TCMSP and related literature, together with the databases of TCMSP, SWISS and STITCH, potential active compounds of Danggui-Baishao were collected, while the targets for cardiovascular diseases were obtained from TTD, OMIM and DrugBank databases. Then the PPI network was screened for the major targets. The KEGG Pathway annotation analyses of major targets were performed by using the DAVID database. The ingredient-major target-key pathway network was constructed by Cytoscape.@*Results@#There were 17 compounds and 54 major targets in the ingredient-target-pathway network, as well as 10 key pathways, including inflammation-related pathway (TNF signaling pathway), pathways related to cardiovascular system (such as PI3K-Akt signaling pathway, FoxO signaling pathway, VEGF signaling pathway, Rap1 signaling pathway), prolactin signaling pathway and estrogen signaling pathway.@*Conclusions@#The study verified the characteristics of multi-components, multi-targets and integral regulation for Danggui-Baishao with the application of network pharmacology. It predicted that Dangui-Baishao couldtreat cardiovascular diseases mainly by regulating angiogenesis, inflammatory response and apoptosis.

Effect of convection enhanced delivery on the microstructure of brain extracellular space in aged rats / 北京大学学报(医学版)

OBJECTIVE@#To compare the changes of extracellular space (ECS) structure and local drug distribution in adult brain and aged brain at different drug delivery rates in minimally invasive treatment of encephalopathy by convection enhanced delivery (CED) via ECS pathway.@*METHODS@#Thirty-six SD male rats were divided into adult rats group (2-8 months, n=18) and aged rats group (18-24 months, n=18) according to the age of the month. According to the drug rates (0.1 μL/min, 0.2 μL/min, and 0.3 μL/min), they were randomly divided into 3 subgroups, 6 in each subgroup. Gadolinium-diethylene triamine pentaacetic acid (Gd-DTPA) with a concentration of 10 mmol/L were introduced into the caudate nucleus of each group of rats by stereotactic injection. Tracer-based magnetic resonance imaging (MRI) was used to dynamically monitor the diffusion and distribution images of the Gd-DTPA in the brain interstitial system (ISS). Using the self-developed MRI image measurement and analysis system software to process and analyze the obtained images, the diffusion coefficient, clearance rate, volume fraction, and half-life of each group of rats in the caudate nucleus ECS could be acquired. The effects and differences of drug clearance and ECS structural function in the brain of aged rats and adult rats were compared and analyzed at different drug delivery rates. Magnetic tracer DECS-mapping technique was used to observe the distribution and drainage of tracer in caudate nucleus.@*RESULTS@#At the injection rate of 0.1 μL/min, the volume fraction in the aged rats was increased compared with that in the adult rats (18.20%±0.04% vs. 17.20%±0.03%, t=3.752, P=0.004), and the degree of tortuosity was decreased (1.63±0.04 vs. 1.78±0.09, t=-3.680, P=0.004), the drug clearance rate was decreased [(1.94±0.68) mm2/s vs. (3.25±0.43) mm2/s, t=-3.971, P=0.003], and the molecular diffusion in ECS was increased [(3.99±0.21)×10-4 mm2/s vs. (3.36±0.37)×10-4 mm2/s, t=3.663, P=0.004]. When the rate of injection increased to 0.2 μL/min, the drug clearance in ECS of the aged rats was slowed down [(2.53±0.45) mmol/L vs. (3.37±0.72) mmol/L, t=-1.828, P=0.021]. However, there were no significant differences in volume fraction, molecular diffusion in ECS and macroscopic drug metabolism parameters. When the rate of injection increased to 0.3 μL/min, the volume fraction in the aged rats was decreased (17.20%±0.03% vs. 18.20%±0.05%, t=-0.869, P=0.045), and the drug clearance rate in ECS was significantly accelerated [(4.04±0.76) mmol/L vs. (3.26±0.55) mmol/L, t=1.786, P=0.014], and there was no significant difference in tortuosity and the rate of molecular diffusion in the ECS.@*CONCLUSION@#The drug clearance and ECS structural parameters of brain ECS in aged brain with CED administration were changed at different rates, and it has the least effect on ECS in the aged brain at the injection rate of 0.2 μL/min. For the application of CED for the treatment of encephalopathy, we should consider the influence of factors such as age and injection rate, and provide reference for the development of individualized clinical treatment plan for minimally invasive treatment of encephalopathy via ECS pathway.

Clinical characteristics of elderly patients with disulfiram-like reaction : a retrospective analysis of 19 cases / 中华老年医学杂志

Objective To analyze the clinical characteristics of elderly patients with disulfiramlike reaction,in order to raise awareness of this disease.Methods Clinical data of 19 elderly patients diagnosed as disulfiram-like reaction in the emergency department of Beijing Hospital from January 2012 to March 2017 were retrospectively analyzed.Disulfiram-like reaction was diagnosed by comprehensive data of the drugs-induced disulfiram-like reaction,related clinical manifestations,auxiliary examination,treatment response,and by differential diagnosis.Results All of 19 patients were male,with one or more chronic disease,mean ± SD age were 75.6±5.1 years.Of 19 patients,16 patients were taking antibiotics,including ceftriaxone,cefoperazone sodium sulbactam,cefpropene,cefuroxime and moxifloxacin,and other patients received warfarin sodium,glimepiride and metformin before the onset of disulfiram-like reaction.Clinical manifestations of disulfiram like reaction mainly involved the cardiovascular system such as palpitation,chest distress,angina,hypotension,etc.,and might be accompanied by dizziness,facial flushing,awareness disorder,gastrointestinal hemorrhage,renal dysfunction,etc.The myocardial ischemia in ECG was observed in 13 patients,the elevated serum troponin in 3 patients,and a continuing organ dysfunction in 1 patient.Conclusions The elderly patients with disulfiram-like reaction are mainly male,with various pathogenic factors and dangerous prognosis.The symptoms of cardiovascular system are obvious,including arrhythmia,myocardial injury,heart failure,shock and other serious cardiovascular complications.

Study on Quality Control Components in Water Extract of Chrysanthemum morifolium and Network Pharmacology Effects / 中国药房

OBJECTIVE： To screen the quality control components of Chrysanthemum morifolium based multiple component metabolism， and study its network pharmacology effect. METHODS： The water extract of C. morifolium was prepared. A total of one rats were selected， water extract of C. morifolium was perfused in jejunum segment after abdominal anesthesia； plasma sample 1 was collected by double perfusion collection. Other 3 rats were given water extract of C. morifolium intragastrically， and plasma sample 2 was collected by abdominal aorta blood collection. UPLC-MS/MS was used to analyze water extract of C. morifolium and plasma sample component， and prototype blood-entry component in water extract of C. morifolium was identified after metabolism. TCMSP and Swiss Target Prediction database were used to screen the core target of prototype blood-entry component. DAVID database was used to enrich the related pathways of core target. The quality control components were screened according to topological parameters. Cytoscape software was used to analyze pharmacological effect of quality control components of C. morifolium. RESULTS： After UPLC-MS/MS analysis， 27 compounds were identified in water extract of C. morifolium， among which there were 12 prototype blood-entry components. After network pharmacology analysis， 7 quality control components were identified， i.e. cosmosiin， apigenin-7-O-glucuronide， luteolin， tilianin， apigenin， hesperetin， acacetin. It was possible to treat cancer， cardiovascular and cerebrovascular diseases， and neurological diseases by acting on metabolic pathway， cancer related pathway， signal transduction related pathway， adipocyte lipolysis regulatory pathway， etc. CONCLUSIONS： The study screen the possible quality control components of water extract of C. morifolium. The theoretical pharmacological effect of it can be clarified through network pharmacology， which can provide a new idea for the utilization of C. morifolium.

NANOG Alleviates the Damage of Human Hair Follicle Mesenchymal Stem Cells Caused by H2O2 through Activation of AKT Pathway / 生物医学与环境科学（英文）

OBJECTIVE@#To explore the protective effect of NANOG against hydrogen peroxide (H2O2) -induced cell damage in the human hair follicle mesenchymal stem cells (hHF-MSCs).@*METHODS@#NANOG was expressed from a lentiviral vector, pLVX-IRES-ZsGreen. NANOG hHF-MSCs and vector hHF-MSCs were treated with 400 μmol/L hydrogen peroxide (H2O2) for 2 h, the cell survival rate, cell morphology, ROS production, apoptosis and expression of AKT, ERK, and p21 were determined and compared.@*RESULTS@#Our results showed that NANOG could activate AKT and upregulate the expression of p-AKT, but not p-ERK. When treated with 400 μmol/L H2O2, NANOG hHF-MSCs showed higher cell survival rate, lower ROS production and apoptosis, higher expression of p-AKT, higher ratio of p-AKT/AKT.@*CONCLUSION@#Our results suggest that NANOG could protect hHF-MSCs against cell damage caused by H2O2 through activating AKT signaling pathway.