Role of apical sodium-dependent bile acid transporter in hepatobiliary diseases / 临床肝胆病杂志

Apical sodium-dependent bile acid transporter （ASBT） is a key transporter responsible for intestinal reabsorption of bile acid and plays an important role in maintaining bile acid and cholesterol homeostasis， and its expression is regulated by various factors including transcription factors， nuclear receptors， and intestinal microflora. The abnormal expression and function of ASBT can lead to disorders in the metabolism of bile acid and cholesterol， causing a variety of hepatobiliary diseases. At present， ASBT has attracted wide attention as a therapeutic target. This article elaborates on the biological characteristics and expression regulation mechanism of ASBT and reviews the role of ASBT in hepatobiliary diseases， in order to provide a new direction for the treatment of related diseases.

Cancer cell membrane-coated bacterial ghosts for highly efficient paclitaxel delivery against metastatic lung cancer

Chemotherapy is one of the major approaches for the treatment of metastatic lung cancer, although it is limited by the low tumor delivery efficacy of anticancer drugs. Bacterial therapy is emerging for cancer treatment due to its high immune stimulation effect; however, excessively generated immunogenicity will cause serious inflammatory response syndrome. Here, we prepared cancer cell membrane-coated liposomal paclitaxel-loaded bacterial ghosts (LP@BG@CCM) by layer-by-layer encapsulation for the treatment of metastatic lung cancer. The preparation processes were simple, only involving film formation, electroporation, and pore extrusion. LP@BG@CCM owned much higher 4T1 cancer cell toxicity than LP@BG due to its faster fusion with cancer cells. In the 4T1 breast cancer metastatic lung cancer mouse models, the remarkably higher lung targeting of intravenously injected LP@BG@CCM was observed with the almost normalized lung appearance, the reduced lung weight, the clear lung tissue structure, and the enhanced cancer cell apoptosis compared to its precursors. Moreover, several major immune factors were improved after administration of LP@BG@CCM, including the CD4+/CD8a+ T cells in the spleen and the TNF-α, IFN-γ, and IL-4 in the lung. LP@BG@CCM exhibits the optimal synergistic chemo-immunotherapy, which is a promising medication for the treatment of metastatic lung cancer.

Effect of the insulated environment on brain function and its therapeutical drugs / 药学实践杂志

The long-term insulated environment (such as burial after earthquakes, trapped elevators, etc.) can affect emotion by affecting neural plasticity and neurotransmitters, while the bad emotions can further affect normal cognition. Drugs can intervene the emotional problems induced by the insulated environment, such as anxiety and depression, and enhance cognitive ability, the negative influence on brain function induced by the insulated environment can be prevented or alleviated. First, the animal model of brain dysfunction in the insulated environment should be established. The cognitive, learning and memory ability can be evaluated by Morris water maze, Barnes maze, etc. The therapeutic drugs mainly include anti-depression/antianxiety drugs and cognition-improving drugs. Saffron, lavender, passion flower and magnesium ion, have shown good anti-anxiety and anti-depression effects and are suitable for the treatment of emotional problems caused by the insulated environment. Methylphenidate and its analogues, piracetam, hypericum perforatum, and salvia officinalis that can enhance cognition can also be used to prevent and treat cognitive disorders such as inattention and memory decline caused by the insulated environment. Elucidating the mechanism of closed environment and finding more effective drugs can provide a more effective solution to the decline of brain function caused by long-term closed environment..

Predatory bacterial hydrogels for topical treatment of infected wounds

Wound infection is becoming a considerable healthcare crisis due to the abuse of antibiotics and the substantial production of multidrug-resistant bacteria. Seawater immersion wounds usually become a mortal trouble because of the infection of Vibrio vulnificus. Bdellovibrio bacteriovorus, one kind of natural predatory bacteria, is recognized as a promising biological therapy against intractable bacteria. Here, we prepared a B. bacteriovorus-loaded polyvinyl alcohol/alginate hydrogel for the topical treatment of the seawater immersion wounds infected by V. vulnificus. The B. bacteriovorus-loaded hydrogel (BG) owned highly microporous structures with the mean pore size of 90 μm, improving the rapid release of B. bacteriovorus from BG when contacting the aqueous surroundings. BG showed high biosafety with no L929 cell toxicity or hemolysis. More importantly, BG exhibited excellent in vitro anti-V. vulnificus effect. The highly effective infected wound treatment effect of BG was evaluated on mouse models, revealing significant reduction of local V. vulnificus, accelerated wound contraction, and alleviated inflammation. Besides the high bacterial inhibition of BG, BG remarkably reduced inflammatory response, promoted collagen deposition, neovascularization and re-epithelization, contributing to wound healing. BG is a promising topical biological formulation against infected wounds.

Nutritional assessment and treatment management of infantile cholestatic liver disease / 临床肝胆病杂志

Children with infantile cholestatic liver disease are often accompanied by malnutrition, which in turn can affect its progression and prognosis. There are many factors causing malnutrition and various methods for malnutrition assessment, but there is still a lack of uniform standard for nutritional assessment in patients with liver diseases, and a variety of indicators and methods are required for comprehensive analysis and assessment. This article analyzes the common causes of malnutrition in children with cholestatic liver disease, introduces the different methods for nutritional assessment, including anthropometric measurements, laboratory examination, and nutritional assessment tools, and elaborates on nutritional intervention treatment, so as to improve the understanding of nutritional problems in children with cholestatic liver disease. Early identification and rational interventions can help to improve the quality of life and prognosis of children.

Characteristics of motor and non-motor symptoms in patients with rapid eye movement sleep behavior disorder and early Parkinson disease / 中华行为医学与脑科学杂志

Objective:To investigate the motor and non-motor symptoms and polysomnographic features in patients with rapid eye movement sleep behavior disorder (RBD), early Parkinson's disease (PD) with and without RBD.Methods:Patients with idiopathic RBD (IRBD) and early PD were collected from the clinics in West China Hospital of Sichuan University from August 2020 to May 2021.All the patients were divided into 3 groups including IRBD group (67 cases), PD with RBD (PD+ RBD) group (19 cases), and PD without RBD (PD-RBD) group (22 cases). Unified Parkinson's disease rating scale part 3 (UPDRS-Ⅲ), Hoehn-Yahr(H-Y) stage, Epworth sleepiness scale (ESS), REM sleep behavior disorder questionnaire-Hong Kong (RBDQ-HK), 17-item Hamilton depression scale(HAMD-17), mini-mental state examination(MMSE), Sniffin’Sticks olfactory function test, visual analogue scale (VAS), and scale for outcomes in Parkinson's disease-AUT(SCOPA-AUT) were used to assess the motor and non-motor symptoms including sleepiness, RBD, depression, cognitive function, olfactory function, pain and autonomic function respectively.All patients were performed to the polysomnography (PSG) examination.One-way ANOVA, Krukal-Wallis test, χ2 test and Fisher accurate test were used to analyze the data of motor and non-motor symptoms and sleep parameters among the 3 groups accordingly. Results:There were statistically significant differences in motor symptoms among the three groups ( F=57.009, P<0.05), and the scores of UPDRS Ⅲ and H-Y stage were higher in the PD+ /- RBD group than those in the IRBD group(both P<0.05). However, there was no significant difference in motor symptoms between PD+ RBD group and PD-RBD group ( P>0.05). There were no significant differences in the scores of ESS, MMSE, olfactory function test and VAS (all P>0.05). But the HAMD-17 score was significantly higher in the PD+ RBD group(2(1, 9)) than that in the IRBD group (0(0, 3)( P<0.05). The SCOPA-AUT scores of autonomic function were significant differences in the three groups, mainly in the digestive system, urinary system, and sexual function ( P<0.05). Notably, the IRBD group (8(4, 14)) and PD+ RBD group (11(7, 14)) had higher scores of SCOPA-AUT compared with PD-RBD group (4(4, 5.75)(all P<0.05), especially in the digestive dysfunction(all P<0.05). The PD+ RBD group(3.47±1.17) had higher scores of sexual function compared with IRBP group(1.78±0.60)( P<0.05), and the urinary system scores also higher than PD-RBD group( P<0.05). The PD-RBD group(21.30 (6.10, 34.00)/h) had a significantly higher oxygen desaturation index in REM sleep compared with that of IRBD group(5.90(2.70, 16.73)/h) ( P<0.05). Conclusions:Early PD with RBD has more severe non-motor symptoms, especially depression and autonomic dysfunction.RBD can be related with the earlier and more widely autonomic dysfunction.

Connotation and scientific research points of processing of Mongolian medicinal materials / 中草药·英文版

Traditional Mongolian medicine (TMM) is an important part of Chinese traditional culture, which plays an important role within the medical system of China. The processing of Mongolian medicinal materials is a pharmaceutical technology, which is the unique characteristics of Mongolian medicine. In this paper, the basic concepts related to the processing of Mongolian medicinal materials were introduced, and its scientific research points were put forward, in order to deeply excavate the connotation of Mongolian pharmacy and further study the processing mechanism of Mongolian medicinal materials, so as to provide important basis for the development of Chinese traditional medicine. The essence of Mongolian medicinal materials processing is to use drugs safely and dialectically to ensure the quality of Mongolian medicinal materials. The scientific research sites of Mongolian medicinal materials processing have two categories: reducing toxicity (increasing) effect and synergistic effect of excipients and processing factors. Because of the not perfect research platform of Mongolian medicinal materials and the weak processing power, the development of research of Mongolian medicinal materials is relatively slow. Therefore, there are many research breakthroughs in the interdisciplinary research on the processing of Mongolian medicinal materials, and it is expected to become a research hotspot.

Mechanisms and therapeutic drugs of high-altitude lung diseases / 药学实践杂志

The heavily harsh plateau environment including low pressure, hypoxia, cold, dryness and strong ultraviolet radiation, seriously threatens the physical and mental health of those who quickly enter the plateau area. Lungs are the sensitive organs for high altitude injury. High-altitude lung diseases include the acute high-altitude lung disease (i.e., high-altitude pulmonary edema), the chronic high-altitude lung disease (i.e., high-altitude pulmonary artery hypertension) and the high-altitude de-adapted reaction. This review summarizes the pathogenic mechanisms and the main therapeutic drugs of high-altitude lung diseases based on the recent research. Moreover, the related formulations and administration routes are also reviewed here. It will provide support and counsel for the diagnosis and treatment of high-altitude lung diseases.

Inhaled curcumin mesoporous polydopamine nanoparticles against radiation pneumonitis

Radiation therapy is an effective method to kill cancer cells and shrink tumors using high-energy X-ray or γ-ray. Radiation pneumonitis (RP) is one of the most serious complications of radiation therapy for thoracic cancers, commonly leading to serious respiratory distress and poor prognosis. Here, we prepared curcumin-loaded mesoporous polydopamine nanoparticles (CMPN) for prevention and treatment of RP by pulmonary delivery. Mesoporous polydopamine nanoparticles (MPDA) were successfully synthesized with an emulsion-induced interface polymerization method and curcumin was loaded in MPDA via π‒π stacking and hydrogen bonding interaction. MPDA owned the uniform spherical morphology with numerous mesopores that disappeared after loading curcumin. More than 80% curcumin released from CMPN in 6 h and mesopores recovered. CMPN remarkably protected BEAS-2B cells from γ-ray radiation injury by inhibiting apoptosis. RP rat models were established after a single dose of 15 Gy 60Co γ-ray radiation was performed on the chest area. Effective therapy of RP was achieved by intratracheal administration of CMPN due to free radical scavenging and anti-oxidation ability, and reduced proinflammatory cytokines, high superoxide dismutase, decreased malondialdehyde, and alleviated lung tissue damages were observed. Inhaled CMPN paves a new avenue for the treatment of RP.

Intranasal temperature-sensitive hydrogels of cannabidiol inclusion complex for the treatment of post-traumatic stress disorder

Post-traumatic stress disorder (PTSD) is a psychiatric disease that seriously affects brain function. Currently, selective serotonin reuptake inhibitors (SSRIs) are used to treat PTSD clinically but have decreased efficiency and increased side effects. In this study, nasal cannabidiol inclusion complex temperature-sensitive hydrogels (CBD TSGs) were prepared and evaluated to treat PTSD. Mice model of PTSD was established with conditional fear box. CBD TSGs could significantly improve the spontaneous behavior, exploratory spirit and alleviate tension in open field box, relieve anxiety and tension in elevated plus maze, and reduce the freezing time. Hematoxylin and eosin and c-FOS immunohistochemistry slides showed that the main injured brain areas in PTSD were the prefrontal cortex, amygdala, and hippocampus CA1. CBD TSGs could reduce the level of tumor necrosis factor-

Effects of intraperitoneal injection of insulin on the regulation of abnormal blood glucose and blood lipid in obese type 2 diabetic KKAy mice / 国际生物医学工程杂志

Objective:To study the effect of insulin intraperitoneal injection on abnormal blood lipid intype 2 diabetic KKAy mice.Methods:Type 2 diabetic mice model was established by feeding high fat and high sugar diet. KKAy model mice were randomly divided into intraperitoneal injection group ( n=6), subcutaneous injection group ( n=6) and no-treatment group ( n=3). At the same time, healthy C57BL/6J mice were selected as normal group ( n=6), and healthy KKAy mice as disease-free group ( n=6). The treatment process was divided into two stages. The first stage consists of 6 weeks, in which the mice in the intraperitoneal and subcutaneous groups were treated with insulin intraperitoneally and subcutaneously respectively. The second stage consists of 4 weeks, in which the mice in intraperitoneal and subcutaneous groups were subcutaneously injected with insulin. The mice in the remaining 3 groups were not treated. The changes of related indicators were detected every two weeks, including body weight, fasting blood sugar, 2 hours after meal blood sugar, triglyceride (TG), total cholesterol (TC), high density lipoprotein cholesterol (HDL-C) and low density lipoprotein cholesterol (LDL-C). Results:Changing the injection solution in the medium term of the treatment had no effect on the body mass and blood sugar of KKAy mice with type 2 diabetes. Under this condition, the effect of intraperitoneal injection of insulin on HDL-C and LDL-C is significantly better than that of subcutaneous injection. Besides, both injection solutions are effective in regulating TG, but the effect of reducing total cholesterol is not obvious.Conclusions:The intraperitoneal injection of insulin has a certain effect on the blood lipid abnormality of type 2 diabetic KKAy mice. It can promote the increase of HDL-C, the decrease of LDL-C, and the decrease of TG.

Establishment and application of animal models of cholestasis / 临床肝胆病杂志

Cholestatic liver disease is one of the common diseases in children aged ＜1 year and has a complex etiology and different outcomes. Various animal models have been established to further investigate the pathogenesis of cholestatic liver disease and related treatment strategies. A model of obstructive cholestasis is established by surgery or external physical and chemical damage; a model of intrahepatic cholestasis is induced by chemicals or endotoxins, including α-naphthyl isothiocyanate, lipopolysaccharide, 3,5-diethoxycarbonyl-1,4-dihydrocollidine, estrogen, chlorpromazine, rifampicin, and lithocholic acid; a model of parenteral nutrition-associated cholestasis is established by a combination of intestinal damage and parenteral nutrition. These models reflect different causes and development processes. This article reviews the characteristics, mechanisms, and indications of animal models of cholestasis commonly used in medical research.

Research on sunscreen lipstick to protect UVA and UVB / 药学实践杂志

Objective To prepare the sunscreen lipstick in order to prevent UVA and UVB.Methods The ratio of bees-wax,castor oil and liquid paraffin were optimized with the orthogonal test based on viscosity and heat resistance.The spread-able ability,stability and the anti-ultraviolet effect of the optimized lipstick were investigated.Results The best ratio of bees-wax,castor oil and liquid paraffin was 8:5:4(w/w/w).The viscosity of the sunscreen lipstick was appropriate,easy to spread and stable,which was demonstrated the good prevention effect from UVA and UVB.Conclusion The advantages of the prepared sunscreen lipstick included simple preparation,low cost and stable quality.It could be a new type of sunscreen lipstick protecting from UVA and UVB.

Effect of physical techniques on in vitro transdermal permeability of sinapine thiocyanate / 国际药学研究杂志

Objective To compare the improvement effect of three physical techniques on the transdermal absorption of sinap?ine thiocyanate(ST)in vitro,including microneedles,sonophoresis and iontophoresis,and to evaluate the mechanism and rules of physcial techniques on the transdermal absorption of poorly transdermal absorbed drugs. Methods In vitro transdermal experiment was carried out under the circumstances of microneedles,sonophoresis or iontophoresis,using the modified Franz diffusion pool. The 2 mg/ml ST solution was adopted as the donor solution, and the SD rats′abdomen skin was used as the model skin. Sampling was car?ried out at the predetermined time points and each sample was analyzed by HPLC. Cumulative transdermal amount and steady transder?mal absorption rate were calculated. Pathological slides were made after the skins were treated with microneedles ,sonophoresis and iontophoresis for 12 h. The structure changes were observed to evaluate the transdermal improvement mechanism of different technolo?gies. Results Accumulated transdermal amount of ST was little without any techniques. The transdermal improvement effect of differ?ent technologies was as follows:microneedles>sonophoresis>iontophoresis. A substantial hole formed on the skin by microneedles to promote ST transdermal absorption obviously. Sonophoresis disrupted the tight structure of skin and improved the transdermal absorp?tion of drugs easily. The effect of iontophresis on skin structure was little. Conclusion This study provides experimental evidence for choice of different techniques to improve transdermal absorption.

Inhalable oridonin-loaded poly(lactic--glycolic)acid large porous microparticles fortreatment of primary non-small cell lung cancer

Non-small cell lung cancer (NSCLC) accounts for about 85% of all lung cancers. Traditional chemotherapy for this disease leads to serious side effects. Here we prepared an inhalable oridonin-loaded poly(lactic--glycolic)acid (PLGA) large porous microparticle (LPMP) fortreatment of NSCLC with the emulsion/solvent evaporation/freeze-drying method. The LPMPs were smooth spheres with many internal pores. Despite a geometric diameter of ~10 µm, the aerodynamic diameter of the spheres was only 2.72 µm, leading to highly efficient lung deposition.studies showed that most of oridonin was released after 1 h, whereas the alveolar macrophage uptake of LPMPs occurred after 8 h, so that most of oridonin would enter the surroundings without undergoing phagocytosis. Rat primary NSCLC models were built and administered with saline, oridonin powder, gemcitabine, and oridonin-loaded LPMPsairway, respectively. The LPMPs showed strong anticancer effects. Oridonin showed strong angiogenesis inhibition and apoptosis. Relevant mechanisms are thought to include oridonin-induced mitochondrial dysfunction accompanied by low mitochondrial membrane potentials, downregulation of BCL-2 expressions, upregulation of expressions of BAX, caspase-3 and caspase-9. The oridonin-loaded PLGA LPMPs showed high anti-NSCLC effects after pulmonary delivery. In conclusion, LPMPs are promising dry powder inhalations fortreatment of lung cancer.

Preparation and properties of docetaxel-loaded nanobubbles / 国际药学研究杂志

Objective To optimize the formulation and preparation technology of docetaxel(DTX)-loaded nanobubbles,and evaluate their properties. Methods The best ratio of methoxypoly(ethylene glycol)-poly(DL-lactide-co-glycolide)(mPEG-PLGA) and different membrane stabilizers were optimized with Langmuir membrane balance. DTX-Loaded nano-micelles were encapsulated by mPEG-PLGA with an injection method. Nanoemulsions was formed after being added with perfluoropentane(PFP,the boiling point of 29.5℃)as the organic phase. The formulations and preparation techniques of nanoemulsions were optimized and the conditions of nanobubbles formulaion was also evaluated. Cytotoxicity of DTX-loaded nanobubbles on MCF-7 cells was evaluated with the MTT meth?od. Results The best ratio of mPEG-PLGA and Span 20 was 10∶1(mol/mol). The membrane elasticity of the prepared nanobubbles with optimized formulations and the preparation techniques was good. In addition,they were obviously temperature-sensitive and ultra?sonic-sensitive. The particle size of nanobubbles increased with higher temperature and decreased with lower temperature. The size of nanobubbles increased upon ultrasound application and then decreased a little. The cytotoxicity of DTX-loaded nanobubbles on MCF-7 cells was obvious and dose-dependent. Conclusion DTX-Loaded nanobubbles are a novel formulation with tumor-targeted and ultra?sound-sensitive drug release.

Curcumin-loaded chitosan liposomes for the treatment of rabbit corneal alkali burns / 国际药学研究杂志

Objective To investigate the effect of the novel curcumin-loaded chitosan liposomes on rabbit alkaline burns. Methods Curcumin-loaded chitosan liposomes were prepared with a film method. The particle sizes,zeta potentials and encapsula?tion efficiencies of liposomes were determined. Rabbits were randomly divided into four groups:the physiological saline group,the blank chitosan coated liposomes group,the dexamethasone group,and the curcumin-loaded chitosan liposomes group. The rabbit cor?neal alkaline burn models were built and respectively processed with the above medicines. The corneal neovascularization(CNV)and proportion of corneal epithelium healing were analyzed with the slit-lamp microscope and digital photographs. The expression of vascu?lar endothelial growth factor(VEGF)was examined with an immunohistochemical method. Results The curcumin-loaded chitosan li?posomes had the particle size of 96.6 ± 14.7 nm,with the average zeta potential of 58.8 ± 2.3 mV,and the encapsulation efficiency of 51.41±1.1%. The CNV was effectively inhibited and the expression of VEGF decreased due to the curcumin-loaded chitosan liposomes and dexamethasone. Furthermore,the curcumin-loaded chitosan liposomes improved epithelial healing of corneal more effectively than dexamethasone. Conclusion The encapsulation efficiency of the curcumin-loaded chitosan liposomes was high. The effects of the cur?cumin-loaded chitosan liposomes on inhibition of CNV and improvement of healing of cornea epithelium were obvious. Curcumin-load?ed chitosan liposomes are novel ophthalmic delivery formulations for the treatment of corneal alkaline burns.

Brain-targeted nasal drug delivery systems for the treatment of neurodegenerative diseases / 国际药学研究杂志

Incidence of neurodegenerative diseases has been increasing year by year in the current aging society which inter?feres the living quality of the patients severely. Pathological changes in neurodegenerative diseases appeare in central nervous system (CNS). The administration route of drugs to treat neurodegenerative diseases becomes a very important scientific research field. Part of drugs may cross over blood-brain barrier(BBB)to CNS by oral or injection administration. But most of drugs are distributed in the oth?er tissues and might cause adverse reactions ,such as gastrointestinal side-effects and arrhythmia. Moreover ,the compliance of the aging patients is poor. They cannot adhere to administer multi-dose drugs for sereral times a day. Nasal drug delivery systems could de?liver drugs to brains directly by nasal-brain route,avoiding BBB with high targeting ratio,high drug availability and good patients′compliance. The review summarizes the major types of neurodegenerative diseases and their current therapeutic methods. The impor?tant obstacles for brain-targeted drug delivery ,nose-brain routes and the factors influencing nasal absorption are introduced. More importantly,the principal formulations,recent research progress and the unsolved problems of brain-targeted nasal drug delivery sys?tems are also reviewed.

Effect of alcohol extract of Cortex Eucommiae on oxidative stress markers in serum of brain aging model mice / 国际药学研究杂志

Objective To explore the effect of Cortex Eucommiae(CE)extract on oxidative stress markers of brain aging mice. Methods Brain aging mice model was made via subcutaneously administered D-galactose. The ethanol extract of CE was intra?gastrically administered to the model mice. Apoptosis ratio of brain cells of mice was determined by a flow cytometry to evaluate the an?ti-aging function of CE extract. A series of biomarkers related to oxidation,including malonyldialdehyde(MDA),superoxide dis?mutase(SOD),protein carbonyl(PCO),and nitric oxide(NO)in serum of mice were determined by ELISA. Results Compared with the model mice,the apoptosis ratio of brain cells in the CE extract group decreased significantly(P<0.01). ELISA test results showed that,compared with the normal group,NO and SOD levels in serum of CE extract group were significantly higher(P<0.01). Compared with the model group,MDA and PCO levels in serum of CE extract group were significantly lower(P<0.01),and SOD level was obviously higher(P<0.01). Conclusion The CE extract might play the role of brain anti-aging by the effective attenuation of ox?idative damage.

Ultrasonic microbubbles for glioma-targeted drug delivery / 药学学报

Ultrasonic microbubbles were used to open blood-brain barriers (BBB) with a reversed and limited behavior feature in the study, which could improve the brain-targeted delivery of anti-tumor drugs. The glioma rat model was prepared. Low-frequency ultrasound was combined with microbubbles to affect the permeability of BBB compared with the permeability of independently administered Evans blue (EB) crossing BBB. Time point and length of ultrasound were investigated whether they affect the permeability of BBB and the damage of brain tissue. The effect of the growth time of glioma on BBB permeability was explored. Only glioma had a very little impact on BBB permeability. However, ultrasonic microbubbles opened the BBB with the features of temporary, limited and reversed behavior and improved EB and magnetic resonance imaging contrast agent penetrating BBB. A length of 30 s ultrasound is appropriate for opening BBB and no damage of brain tissue. Drugs should be injected before ultrasound so that they enter into brain as BBB opening. Ultrasonic microbubbles can open BBB effectively and safely, which improve drugs penetrating BBB under proper time point and length.