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Sleep disorders are one of the most common acute reactions on the plateau, which can cause serious complications. However, there is no effective and safe treatment currently available. Nimodipine (NMD) is a dihydropyridine calcium channel blocker with neuroprotective and vasodilating activity, mainly used for the treatment of ischemic brain injury. Commercial oral or injectable NMD formulations are not a good option for central neuron diseases due to their poor brain delivery. In this study, nimodipine dissolving microneedles (NDMNs) were prepared for the prevention of sleep disorders caused by hypoxia. NDMNs were composed of NMD and polyvinyl pyrrolidone (PVP) K90 with a conical morphology and high rigidity. After administration of NDMNs on the back neck of mice, the concentration of NMD in the brain was significantly higher than that of oral medication as was confirmed by the fluorescent imaging on mouse models. NDMNs enhanced cognitive function, alleviated oxidative stress, and improved the sleep quality of mice with high-altitude sleep disorders. The blockage of calcium ion overloading may be an important modulation mechanism. NDMNs are a promising and user-friendly formulation for the prevention of high-altitude sleep disorders.
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Bloqueadores dos Canais de Cálcio , Nimodipina , Transtornos do Sono-Vigília , Animais , Camundongos , Nimodipina/administração & dosagem , Transtornos do Sono-Vigília/tratamento farmacológico , Transtornos do Sono-Vigília/prevenção & controle , Masculino , Bloqueadores dos Canais de Cálcio/administração & dosagem , Altitude , Agulhas , Encéfalo/metabolismo , Encéfalo/efeitos dos fármacos , Sistemas de Liberação de Medicamentos/métodos , Estresse Oxidativo/efeitos dos fármacos , Povidona/química , Camundongos Endogâmicos C57BLRESUMO
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.
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BACKGROUND:Combined radiation and wound injury appeared mainly in patients with tumor radiotherapy and nuclear radiation accidents.The radiation destroys the repair mechanism,resulting in delayed or prolonged wound healing.It still lacks an effective therapeutic strategy currently. OBJECTIVE:To prepare multifunctional wound dressings based on the multiple clinical symptoms of combined radiation and wound injury,which are designed to be antibacteria,promoted healing and analgesics. METHODS:Using levofloxacin,fibroin and lidocaine hydrochloride as raw materials,3D bioprinting technology was applied to prepare the multifunctional wound dressing.(1)The multifunctional dressing was placed on a fixed culture plate coated with Staphylococcus aureus,Escherichia coli and Pseudomonas aeruginosa,and incubated at 37 ℃ overnight to detect the diameter of the antibacterial zone.(2)40 Kunming mice were randomly divided into trauma group,radiation and trauma model group,treatment group and positive drug group,with 10 mice in each group.Mice in the radiation and trauma model group,treatment group and positive drug group were irradiated by 60Co gamma rays.After 1 hour of radiation,a full-layer skin defect wound with a diameter of 1 cm was made on the back of each mouse in the four groups.Normal saline was applied to the wounds of the trauma group and the radiation and trauma model group.Trethanolamine cream was applied to the wounds of the positive drug group.Multifunctional dressing was applied to the wounds of the treatment group.The dressing was changed every 2 days,and the treatment was continued for 14 days.Wound healing rate and serum interleukin-6 level were measured at 3,7 and 14 days after wound modeling.14 days after the wound modeling,the skin tissue of the wound was obtained and received hematoxylin-eosin staining,Masson staining and cytokeratin-14 immunohistochemical staining. RESULTS AND CONCLUSION:(1)3D-printed multifunctional wound dressing had good antibacterial activity.The antibacterial zone diameters against Staphylococcus aureus,Escherichia coli and Pseudomonas aeruginosa were(4.15±0.09),(4.18±0.23)and(4.35±0.13)cm,respectively.(2)With the extension of modeling time,the wound healed gradually.The wound healing rate of the treatment group and the positive drug group was higher than that of the radiation and trauma model group at 3,7 and 14 days after modeling(P<0.01,P<0.001).The wound healing rate of the treatment group was higher than that of the positive drug group.With the extension of modeling time,the serum interleukin level of mice increased first and then decreased.The serum interleukin level in the treatment group at 3,7 and 14 days after modeling was lower than that in the radiation and trauma model group.Hematoxylin-eosin staining and Masson staining exhibited that inflammatory cells infiltrated the granuloma tissue in the trauma group,and the dermal collagen fibers were densely arranged.The normal structure of epidermis and dermis was destroyed and inflammatory cells were infiltrated in the radiation and trauma model group.In the treatment group,normal skin mucosal tissue was observed,the epidermis was arranged closely,and the sweat glands,hair follicles and dermal collagen fibers were arranged regularly.In the positive drug group,the arrangement of epidermal layer was tight,and the arrangement of sweat glands,hair follicles and dermal collagen fibers was regular.Cytokeratin-14 immunohistochemical staining displayed that the epidermal tissue thickness in the treatment group was lower than that in the other three groups(P<0.01,P<0.001).(3)The results confirm that the 3D-printed multifunctional dressing has multiple functions of local anesthesia,anti-infection and promoting healing.
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The cognitive impairment of diabetes mellitus type 2(T2DM)is closely related to neurovascular coupling(NVC)changes,but the exact mechanism remains unclear.Functional MRI(fMRI)technology were able to jointly analyze NVC changes of T2DM,providing new ideas for revealing the mechanism of cognitive dysfunction caused by T2DM.The progresses of fMRI for exploring NVC changes in T2DM were reviewed in this article.
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BACKGROUND:Frog active peptides have rich activities,such as antibacterial and anti-tumor,and are expected to solve the problem of antibiotic resistance. OBJECTIVE:The active peptide QUB2984 was discovered in the skin secretions of Agalychnis callidryas.Its structure and properties were simulated by bioinformatics.The peptide was synthesized,purified,and identified and its biological functions were investigated. METHODS:Agalychnis callidryas skin secretions were collected by electrostimulation.The sequence of QUB2984 was obtained through constructing a cDNA library with isolated mRNA.BLAST was used for peptide sequence alignment.Besides that,Iterative Threading ASSEmbly Refinement(I-TASSER)and HeliQuest tools were used for protein secondary structure simulation.It was synthesized by solid-phase peptide synthesis,purified by reverse-phase high-performance liquid chromatography,and structurally confirmed by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry.The purified peptide was used to evaluate its biological activity.Its antibacterial effect was evaluated by the minimum inhibitory concentration method.Its cytotoxic effect was detected by MTT assay.Its safety was investigated by a hemolysis test. RESULTS AND CONCLUSION:(1)Peptide QUB2984 had basically α-spiral structure,with a relatively intact hydrophobic surface,and a certain destructive ability to biofilm.The third amino acid position of QUB2984 was composed of W and had a G-X-G structure.(2)The minimum inhibitory concentration of QUB2984 against gram-positive Staphylococcus aureus was 2 μmol/L,the minimum inhibitory concentration against gram-negative Escherichia coli was 2 μmol/L,and the minimum inhibitory concentration against the fungus Candida albicans was 8 μmol/L.(3)The active peptide QUB2984 had obvious inhibitory effect on human non-small cell lung cancer cells NCI-H838 at 10-5 mol/L concentration,and the hemolytic effect on horse red cells at 64 μmol/L concentration was 50%.(4)The results showed that QUB2984 had anti-bacterial and anti-cancer activity,and it had a positive charge of +3,which was conducive to contact with bacteria or cells.
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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.
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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..
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Objective To rapidly identify and assign the chemical components in Sugemule-4 decoction by using UPLC Orbitrap Exploris MS/MS,and then conduct network pharmacological analysis,and clarify the anti-insomnia effect of Sugmule-4 decoction.Methods ACQUITY UPLC BEH C18(2.1 mm×100 mm,1.7 μm)Chromatographic column,with 0.1%formic acid aqueous solution(A)-0.1%formic acid acetonitrile solution(B)as mobile phase gradient elution.Flow rate:0.5 mL·min-1,injection volume:5 μL.Under the control of the control software(Xcalibur,Thermo Fisher Scientific),the primary and secondary mass spectrometry data are collected based on the FullScan-ddMS2 function.Combined with the self-built database and online database,the chemical components in Sugemule-4 decoction are identified by accurate relative molecular weight,fragment ion information,pyrolysis pattern and comparison of control samples.The identified chemical components were analyzed by network pharmacology,and the targets of drug and insomnia were obtained from TCMSP,SwissTargetPrediction,GeneCards,OMIM,TTD,DrugBank and DisGeNET databases respectively,and the intersection target was obtained;Protein interaction analysis was performed through STRING database.Use Metascape platform to analyze GO function and KEGG pathway,and predict the mechanism of Sugmule-4 decoction in treating insomnia.To determine the anti-insomnia effect of Sugmule-4 decoction,SD rats were divided into normal control group(K),model group(M),Sugmule-4 decoction group(S)and Anshenbunao liquid group(A).After chronic unpredictable mild stress and PCPA were used for modeling,the rats were given corresponding drugs by gavage for 7 days,then the open field text was conducted to observe the general state and behavioral changes,and detection of AChE,5-HT,and GABA levels in serum and brain tissue of rats in each group using ELISA method.Results 136 components were identified from Sugemule-4 decoction,including 37 terpenoids,34 alkaloids,26 flavonoids,20 phenylpropanoids,14 phenolic acids and 5 amino acids.The results of network pharmacology analysis show that the mechanism of Sugemule-4 decoction in treating insomnia is mainly achieved by its components such as Romucosine D,Nornantenine,Nuciferine,and(R)-ar Turbone acting on targets such as ACHE,ADORA2A,and CHRM1 through signal pathways such as Neuroactive ligand-receptor interaction,synaptic signaling,and trans synaptic signaling.This is a multi component-multi target-multi signal pathway joint implementation process.The results of pharmacodynamic experiment showed that Sugmule-4 decoction and Anshenbunao liquid could revise the general state and behavioral changes of insomnia model rats,increase the content of AChE,5-HT and GABA in serum(P<0.01).Conclusion This study comprehensively reflects the chemical components of Sugmule-4 decoction,and preliminarily summarizes the mass spectrum decomposition characteristics of various chemical components.The network pharmacology and pharmacodynamics experiments show that Sugmule-4 decoction has significant anti-insomnia effect,which provides a reference basis for the quality control and mechanism study of Sugmule-4 decoction.
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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.
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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.
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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.
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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.
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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.
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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.
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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-
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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.
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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.
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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.
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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.
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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.