Application research and design strategy on smart responsive mesoporous silica anti-tumor nanodelivery systems / 药学学报

Malignant tumors are major diseases that endanger human health. Due to their complex and variable microenvironment, most anti-tumor drugs cannot precisely reach the focal tissue and be released in a controlled manner. Intelligent responsive nano carriers have become a hot spot in the field of anti-tumor drug delivery systems. As an excellent nano material, mesoporous silica has the advantages of non-toxic, stable, adjustable pore volume and pore diameter, and easy functional modification on the surface. By virtue of its perceptive response to the tumor microenvironment or physiological changes, it can achieve the targeted drug release or controlled drug release of the drug delivery system in the tissue, making it an ideal carrier for intelligent response drug delivery system. In this paper, we review the design strategies and current research status of smart responsive anti-tumor drug delivery systems based on mesoporous silica, in order to provide a reference for the development of anti-tumor drug nanoformulations.

Mechanism of Sijunzi Decoction in treatment of Alzheimer's disease based on UPLC-Q-TOF-MS, network pharmacology, and experimental verification / 中国中药杂志

The study identified the blood-entering components of Sijunzi Decoction after gavage administration in rats by UPLC-Q-TOF-MS/MS, and investigated the mechanism of Sijunzi Decoction in treating Alzheimer's disease by virtue of network pharmacology, molecular docking, and experimental verification. The blood-entering components of Sijunzi Decoction were identified based on the mass spectra and data from literature and databases. The potential targets of the above-mentioned blood-entering components in the treatment of Alzheimer's disease were searched against PharmMapper, OMIM, DisGeNET, GeneCards, and TTD. Next, STRING was employed to establish a protein-protein interaction(PPI) network. DAVID was used to perform the Gene Ontology(GO) annotation and the Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment. Cytoscape 3.9.0 was used to carry out visual analysis. AutoDock Vina and PyMOL were used for molecular docking of the blood-entering components with the potential targets. Finally, the phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt) signaling pathway enriched by the KEGG analysis was selected for validation by animal experiments. The results showed that 17 blood-entering components were detected in the serum samples after administration. Among them, poricoic acid B, liquiritigenin, atractylenolide Ⅱ, atractylenolide Ⅲ, ginsenoside Rb_1, and glycyrrhizic acid were the key components of Sijunzi Decoction in treating Alzheimer's disease. HSP90AA1, PPARA, SRC, AR, and ESR1 were the main targets for Sijunzi Decoction to treat Alzheimer's disease. Molecular docking showed that the components bound well with the targets. Therefore, we hypothesized that the mechanism of Sijunzi Decoction in treating Alzheimer's disease may be associated with the PI3K/Akt, cancer treatment, and mitogen-activated protein kinase(MAPK) signaling pathways. The results of animal experiments showed that Sijunzi Decoction significantly attenuated the neuronal damage in the hippocampal dentate gyrus area, increased the neurons, and raised the ratios of p-Akt/Akt and p-PI3K/PI3K in the hippocampus of mice. In conclusion, Sijunzi Decoction may treat Alzheimer's disease by activating the PI3K/Akt signaling pathway. The findings of this study provide a reference for further studies about the mechanism of action and clinical application of Sijunzi Decoction.

Higher visceral adiposity index is associated with increased likelihood of abdominal aortic calcification

Abstract Background: The negative effects of visceral adiposity accumulation on cardiovascular health have drawn much attention. However, the association between the Visceral Adiposity Index (VAI) and Abdominal Aortic Calcification (AAC) has never been reported before. The authors aimed to investigate the association between the VAI and AAC in US adults. Methods: Cross-sectional data were derived from the 2013 to 2014 National Health and Nutrition Examination Survey (NHANES) of participants with complete data of VAI and AAC scores. Weighted multivariable regression and logistic regression analysis were conducted to explore the independent relationship between VAI and AAC. Subgroup analysis and interaction tests were also performed. Results: A total of 2958 participants were enrolled and participants in the higher VAI tertile tended to have a higher mean AAC score and prevalence of severe AAC. In the fully adjusted model, a positive association between VAI and AAC score and severe AAC was observed (β = 0.04, 95% CI 0.01‒0.08; OR = 1.04, 95% CI 1.01‒1.07). Participants in the highest VAI tertile had a 0.41-unit higher AAC score (β = 0.41, 95% CI 0.08‒0.73) and a significantly 68% higher risk of severe AAC than those in the lowest VAI tertile (OR = 1.68, 95% CI 1.04‒2.71). Subgroup analysis and interaction tests indicated that there was no dependence for the association of VAI and AAC. Conclusion: Visceral adiposity accumulation evaluated by the VAI was associated with a higher AAC score and an increased likelihood of severe AAC.

A case of high-temperature steel bar penetration injury from scrotum to buttocks / 中华烧伤杂志

On November 17, 2013, the Second Affiliated Hospital of Kunming Medical University admitted a 23-year-old male patient with a high-temperature steel bar penetration injury from scrotum to buttocks who was transferred from another hospital. Expanded debridement, suture, and drainage of the perineum, right thigh, and right hip were performed as soon as possible after admission. A sputum suction tube was used as the guide mark for expanded debridement during the operation to ensure the accuracy of the direction and scope of expanded debridement. The incision was treated with vacuum sealing drainage (VSD) and full drainage. On the 20th day after the operation (the 25th day after admission), the unhealed wound was transplanted with split-thickness skin graft from the right thigh, and the drainage of the operation area and dressing change were strengthened. On the 53rd day after injury, the patient was discharged after complete wound healing. This case suggests that VSD after early debridement is an effective means to treat high-temperature steel bar penetration injuries.

Mechanism of tanshinone IIA to prevent spontaneous breast cancer in mice / 药学学报

To explore the effect of tanshinone IIA (TanIIA) on the occurrence and development of breast cancer, we employed the mouse mammary tumor virus-polyomavirus middle T antigen (MMTV-PyMT) transgenic mice as a spontaneous breast cancer mouse model. Animal welfare and experimental procedures were in accordance with the regulations of the Animal Ethics Committee of Nanjing University of Chinese Medicine. The animals were divided into control group, low-dose TanIIA treatment group (30 mg·kg-1·day-1), and high-dose TanIIA treatment group (60 mg·kg-1·day-1). The treatment was administered orally and daily for 5 weeks. The mice were sacrificed after final treatment. Mammary gland and lung were collected for histopathology studies. We evaluated the chemoprophylaxis effect of TanIIA on breast cancer in mice according to the pathological characteristics of breast cancer at different stages of development. Immunofluorescence staining were employed for blood vessel analysis. The expression levels of E-cadherin, proliferating nuclear antigen (PCNA), and oncogene c-Myc were detected by immunohistochemistry. Flow cytometry was used to analyze cell cycle and Cytoscape was used to construct drug-disease protein-protein interaction (PPI) network. Our results showed that TanIIA inhibits breast tumor progression by delaying malignancy from adenoma to early carcinoma, and inhibits blood vessel formation during tumor development. TanIIA (60 mg·kg-1·day-1) inhibits the expression levels of PCNA and c-Myc, upregulates the expression of E-cadherin. In addition, cell cycle experiments showed that the cell cycle of PyMT primary mammary cells in the high-dose TanIIA group was arrested in the G0/G1 phase. Our study demonstrated that TanIIA can significantly inhibit breast tumor progression in MMTV-PyMT mouse model, which may be related to the inhibition of angiogenic switch and cell cycle arrest.

Efficacy of Different Doses of Daunorubicin Induced Chemotherapy in Patients with Newly Diagnosed Primary Acute Myeloid Leukemia Under 65 Years Old / 中国实验血液学杂志

OBJECTIVE@#To compare the efficacy and safety of different doses of daunorubicin combined with a standard dose of cytarabine as induction chemotherapy in newly diagnosed primary acute myeloid leukemia (AML) patients.@*METHODS@#The clinical data and outcome were retrospectively analyzed in 86 newly diagnosed primary AML patients who were under 65 years old and treated with daunorubicin combined with cytarabine (DA regimen) at West China Hospital of Sichuan University from January 2017 to June 2019. Patients were divided into 2 groups based on the dose of daunorubicin they received, 35 cases in the escalated-dose group ［75 mg/(m@*RESULTS@#Median follow-up time of all the patients was 15 months. The CR rate and MRD@*CONCLUSION@#The escalated dose of daunorubicin can induce higher complete remission rate, deeper remission and longer duration of remission without increasing adverse events in newly diagnosed primary AML patients.

Finite element analysis of different intramedullary fixation methods for the treatment of senile pubic ramus fractures / 中国骨伤

OBJECTIVE@#To evaluate the biomechanical stability of elastic intramedullary nail in the treatment of pubic ramus fractures by finite element analysis, and to compare the stability of elastic intramedullary nail with cannulated screw intramedullary fixation.@*METHODS@#The CT data of the pelvis of a volunteer were selected, and the three-dimensional model of the pelvis was reconstructed by reverse engineering software and the fracture of the pubic ramus fractures was simulated by osteotomy. The hollow nail model, single elastic nail model and double elastic nailmodel were assembled with different implants respectively. The mesh division, material assignment loading and other steps were carried out in the ANSYS software, and then the calculation was submitted.@*RESULTS@#The overall displacement of the pelvis of the elastic nail model was smaller than that of the cannulated screw model, in which the double elastic nail model had the smallest overall displacement, but the cannulated screw model had the smallest plant displacement and the single elastic nail model had the largest plant displacement. Although the stress of cannulated screw was small, there was obvious stress concentration, the stress of elastic nail was large, but there was no obvious stress concentration, especially the stress distribution of double elastic nail was more uniform and the overall stress of pelvis was the smallest.@*CONCLUSION@#All the three fixation methods can effectively improve the stability of the anterior ring of the pelvis. Among them, there is no significant difference in the overall biomechanical propertiesof hollow nail fixation and double elastic nail fixation, which is better than that of single elastic nail fixation. Elastic nail fixation has the advantages of minimally invasive surgery and good biomechanical stability, so it can be used as a better surgical method for the treatment of pubic ramus fractures.

Mechanism of volatile oil from Alpinia oxyphylla in treating Alzheimer's disease based on GC-MS and network pharmacology / 中国中药杂志

To study the material basis and mechanism of volatile oil from Alpinia oxyphylla in treating Alzheimer's disease(AD) based on GC-MS and network pharmacology. Ingredients of volatile oil from A.oxyphylla were analyzed by GC-MS. Targets of those ingredients were obtained through Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP). Relevant targets of AD were obtained through such databases as DrugBank, STITCH, OMIM. Intersection targets of ingredients and diseases were obtained by Online Venny map, and PPI network was established by STRING to screen out core targets. Gene ontology(GO) functional enrichment analysis and KEGG pathway enrichment analysis were performed by DAVID. The "ingredients-target-pathway" network was constructed by software Cytoscape 3.8.1 to screen out potential active ingredients of volatile oil from A.oxyphylla in the treatment of AD. The results showed that a total of 6 active ingredients were screened from the volatile oil of A.oxyphylla by GC-MS, 17 targets corresponding to 6 active ingredients were found in TCMSP database, and 3 448 AD targets were found in DrugBank database. "Ingredients-target-pathway" network and PPI network showed there were 4 potential active ingredients in the treatment of AD and 4 core targets. GO analysis and KEGG analysis showed 34(P<0.05) and 5(P<0.05) pathways, respectively, including nerve ligand receptor interaction, calcium signaling pathway, cholinergic synapse and 5-hydroxytryptaminergic synapse. This suggested that volatile oil from A.oxyphylla could synergistically treat AD by regulating calcium balance, cholinergic balance and phosphorylation. This study provided reference and guidance for further study of volatile oil from A.oxyphylla in the treatment of AD.

Research progress and thinking on improving physicochemical properties and efficacy of the active ingredients in traditional Chinese medicine based on crystal structure / 药学学报

The active ingredients in traditional Chinese medicine have been reported to possess significant pharmacological activity and played an important role in clinical treatments. However, lots of the active ingredients in traditional Chinese medicine suffer from disadvantages such as low solubility, high melting point and low stability that results in low bioavailability and limit its clinical application. Crystal structure plays an important role in improving physicochemical properties and efficacy of the active ingredients in traditional Chinese medicine. This review concludes the research advances of several crystal forms used in the active ingredients in traditional Chinese medicine in terms of polymorph, cocrystal, amorphous/coamorphous and nanocrystal. And the effects of crystal forms on the physicochemical properties and efficacy of the active ingredients in traditional Chinese medicine were reviewed. This research may be useful for the formulation preparation and development of the active ingredients in traditional Chinese medicine.

Prediction of Q-markers of Citri Reticulatae Pericarpium volatile oil and GC-MS based quantitative analysis / 中国中药杂志

This study was designed to predict the Q-markers of Citri Reticulatae Pericarpium volatile oil and conduct quantitative analysis by GC-MS. The common components of Citri Reticulatae Pericarpium volatile oil were detected by GC-MS. The network pharmacology approaches were utilized for constructing the component-target network and protein-protein interaction(PPI) network, followed by the GO and KEGG pathway enrichment analysis to clarify the pharmacological effects of common components. Molecular docking was conducted to observe the biological activities of common components, thus identifying the Q-markers of Citri Reticulatae Pericarpium volatile oil. The obtained Q-markers were subjected to quantitative analysis by GC-MS. The GC-MS analysis of 19 batches of Citri Reticulatae Pericarpium volatile oil revealed three common components, namely, D-limonene, γ-terpinene, and myrcene. The common components were analyzed based on network pharmacology, and the results showed that Citri Reticulatae Pericarpium volatile oil mainly acted on the core targets GABRA1, GABRA6, GABRA5, GABRA3, and GABRA2 through D-limonene and γ-terpinene, with five important pathways such as nicotine addiction and GABAergic synapse involved. The core targets were mainly distributed in olfactory region, cerebral cortex, cerebellum, basal ganglia, hippocampus, and amygdala to exert the pharmacological effects. As revealed by molecular docking, D-limonene and γ-terpinene exhibited good biological activities, so they were identified as the Q-markers of Citri Reticulatae Pericarpium volatile oil. The results of quantitative analysis showed that the volume fraction of D-limonene was within the range of 0.77-1.03 μL·mL~(-1), and that of γ-terpinene within the range of 0.04-0.13 μL·mL~(-1). The prediction of D-limonene and γ-terpinene as the Q-markers of Citri Reticulatae Pericarpium volatile oil has laid an experimental foundation for the establishment of the quality evaluation standard for Citri Reticulatae Pericarpium volatile oil.

Analysis of clinical characteristics and related gene mutation characteristics in a case of maple syrup urine disease / 中华实用儿科临床杂志

The clinical characteristics and gene mutation characteristics of a child with typical maple syrup urine disease were analyzed retrospectively.The child is a boy, who showed unexplained milk refusal, poor reaction, foaming at the mouth, and encephalopathy symptoms 7 days after birth.The total leucine concentration was abnormally increased by blood tandem mass spectrometry, and the results of urine gas chromatography/mass spectrometry suggested that the concentrations of 2-hydroxy isovaleric acid, 2-keto isovaleric acid, 2-keto-3-methylpentanoic acid and 2-keto-isohexanoic acid were significantly increased.The gene detection results showed that c. 1028delC (p.S343Lfs*9) homozygous mutation was found in the BCKDHB gene.Understanding the clinical symptoms and gene mutation characteristics of this disease can help with the early detection and early diagnosis of this disease, so as to improve its prognosis to the greatest extent.

Progress of hepcidin in low-risk myelodysplastic syndromes / 白血病·淋巴瘤

Ineffective hematopoiesis, inflammation and iron overload are involved in the regulation of iron metabolism in myelodysplastic syndromes (MDS). Different types of MDS present different iron states at different stages, hepcidin play a key role in it. Current studies have demonstrated that iron metabolism abnormality is an independent risk factor for the prognosis of low-risk MDS. This article summarizes the research progress of hepcidin in patients with low-risk MDS and further explores the therapeutic prospects of hepcidin in patients with low-risk MDS.

Effect of Sijunzi Decoction on regulation of Aβ-related proteins across blood-brain barrier / 中国中药杂志

According to traditional Chinese medicine, "spleen transport" is closely related to the metabolism of substance and energy. Studies have shown that Alzheimer's disease(AD) is a disease related to glucose and lipid metabolism and energy metabolism. The traditional Chinese medicine Jiangpi Recipe can improve the learning ability and memory of AD animal model. Sijunzi Decoction originated from Taiping Huimin Hefang Prescription is the basic prescription for strengthening and nourishing the spleen, with the effects of nourishing Qi and strengthening the spleen. In this experiment, human brain microvascular endothelial cells(HBMEC) and Sijunzi Decoction water extract(0.25, 0.5, 1 mg·L~(-1)) were pre-incubated for 2 h, and then Aβ_(25-35) oligomers(final concentration 40 μmol·L~(-1)) was added for co-culture for 22 hours. The effect of Sijunzi Decoction on the activity of Aβ_(25-35) oligomer injured cells and the expression of related proteins were investigated. Q-TOF-LC-MS was used first for principal component analysis of Sijunzi Decoction water extract. Then MTT assay was used to investigate the effect of Sijunzi Decoction water extract on the proliferation of HBMEC cells. Real-time fluorescence quantitative PCR(RT-qPCR) was employed to detect the mRNA expression of GLUT1, RAGE, and LRP1. The expression of Aβ-related proteins across blood-brain barrier(RAGE, LRP1) was detected by Western blot. The results showed that 40 μmol·L~(-1) Aβ_(25-35) oligomers could induce endothelial cell damage, reduce cell survival, increase expression of RAGE mRNA and RAGE protein, and reduce expression of GLUT1 mRNA, LRP1 mRNA, and LRP1 protein. Sijunzi Decoction water extract could reduce the Aβ_(25-35) oligomer-induced cytotoxicity of HBMEC, decrease the expression of RAGE mRNA and RAGE protein, and increase the expression of GLUT1 mRNA, LRP1 mRNA and LRP1 protein. The results indicated that Sijunzi Decoction could reduce the injury of HBMEC cells induced by Aβ_(25-35) oligomer, and regulate the transport-related proteins GLUT1, RAGE and LRP1, which might be the mechanism of regulating Aβ_(25-35) transport across the blood-brain barrier.

Investigation of Relationship Between Spleen and Alzheimer' s Disease Based on Glucose, Lipid and Energy Metabolisms / 中国实验方剂学杂志

Alzheimer' s disease (AD) is a chronic neurodegenerative disease, which is seriously affecting people' s lives. Until now, the pathogenesis of AD is still unknown which result in its worldwide difficulties in prevention and treatment. Some studies have shown that AD might be a metabolic disease associated with glucose, lipid and energy metabolisms. Traditional Chinese medicine (TCM) believes that the spleen is acquired foundation and the origination of Qi and blood. The function of spleen is not only closely related to the metabolism of substance and energy, but also related to the aging of human body. In this article, we summarized and analyzed the interrelationship of metabolism, AD and spleen, as well as the effect of spleen-invigorating prescription on AD. The purpose of the paper is to analyze the possible mechanism of TCM treating AD from the perspective of regulating metabolism, explore the potential value of spleen-strengthening TCM in the treatment or prevention of AD, and provide new ideas for exploring the drug development and TCM therapy of AD.

Effect of Zhenxin Shengshui Yizhi Fang on Damage of Human Brain Microvascular Endothelial Cells Induced by Aβ25-35 / 中国实验方剂学杂志

Objective::To observe the neuroprotective effect and potential mechanism of Zhenxin Shengshui Yizhi Fang(XSF) aqueous extract on human brain microvascular endothelial cells (HBMEC) injury induced by amyloid-β protein(Aβ)25-35. Method::HBMEC cells damage induced by Aβ25-35 was used as Alzheimer' s disease(AD) cell model. The study included control group, Aβ25-35 group, and low, medium and high-dose XSF aqueous extract groups (125, 250, 500 mg·L-1). After treatment, the cytotoxicity of different concentrations of drugs and Aβ25-35 was determined by methyl thiazolyl tetrazolium(MTT) colorimetry. Apoptosis was observed by Hoechst-33258 staining. The activity of Caspase-3 was detected by colorimetry. Western blot was used to detect the expression levels of the receptor of advanced glycation end products (RAGE) and low-density lipoprotein receptor-related protein (LRP1). Result::Compared with the control group, the cell viability of Aβ25-35 group was significantly decreased (P<0.01). Hoechst-33258 staining showed bright blue fluorescence, chromatin condensation, dense staining or fragmentation dense staining, whitening in color, and significant increase of the percentage of apoptotic cells (P<0.01). Caspase-3 activity increased significantly (P<0.01). Western blot showed that RAGE protein expression increased significantly (P<0.01), while low-density lipoprotein receptor-related protein(LRP1), glucose transporter 1(GLUT1) and GLUT3 protein expressions decreased significantly (P<0.01). Compared with the Aβ25-35 group, the cell viability of XSF aqueous extract groups was significantly increased in a dose-dependent manner. The XSF aqueous extract had a more significant protective effect of than the other groups (P<0.05). The XSF aqueous extract group (500 mg·L-1) significantly inhibited the number of apoptotic cells (P<0.01), but significantly reduced the Caspase-3 activity (P<0.01). RAGE protein expression was not significantly decreased in XSF aqueous extract group (125 mg·L-1), but significantly decreased in XSF aqueous extract group (250, 500 mg·L-1, P<0.01), while LRP1, GLUT1 and GLUT3 protein expression significantly increased (P<0.05, P<0.01) in a dose-dependent manner. Conclusion::XSF aqueous extract can attenuate the cytotoxicity of HBMEC induced by Aβ25-35 oligomer, inhibit apoptosis, decrease caspase-3 activity and RAGE protein expression, increase LRP1, GLUT1 and GLUT3 protein expressions, and reduce the abnormal accumulation and deposition of Aβ in the brain, which may be its mechanisms for prevention and treatment of AD.

Study on the correlation between blood glucose fluctuation and body mass index in patients with type 2 diabetes mellitus / 医学研究生学报

ObjectiveThere are few reports on the correlation between blood glucose fluctuation and body mass index(BMI) in patients with type 2 diabetes mellitus (T2DM). This study aims to evaluate the correlation between the two by comparing the differences of glucose fluctuation in T2DM patients with different BMI.MethodsA total of 672 patients with T2DM admitted to the General Hospital of Eastern Theater Command from June 2017 to October 2018 were selected as subjects. They were divided into 4 groups according to the quartile of BMI. The age, height, weight, course of diabetes, hemoglobin, uric acid, glycosylated hemoglobin, HOMA-IR (insulin resistance index) and HOMA-β (islet β cell function index) were collected. The blood glucose of the patients was continuously monitored within 3 days by wearing a continuous glucose monitor (CGMS). The standard deviation of daily blood glucose (SBDG), the mean of daily differences (MODD) and the mean amplitude of glycemic excursion(MAGE) were calculated to analyze the effect of BMI on blood glucose fluctuation.ResultsThe index of blood glucose fluctuation was negatively correlated with BMI, HbA1c and HOMA-β, but positively with HOMA-IR. Compared with the 1st and 2nd quartiles of BMI, the fluctuation level of patients in the 3rd and 4th quartiles was lower. Multivariate logistic regression analysis showed that after adjustment of age, sex, cholesterol, triglyceride and hemoglobin, the risk of hyperglycemia fluctuation in the fourth quartile group was lower than that in the first quartile group (OR=0.594, 95%CI: 1.825~2.062).ConclusionThe fluctuation of blood glucose in patients with higher BMI is lower than that in patients with lower BMI.

Effect of Zhenxin Xingshui Yizhi Fang and Its Essential Oil Extract on Ability of Learning and Memory in Alzheimer's Disease Model Mice / 中国实验方剂学杂志

Objective: The present study was designed to investigate the modulating effect of Zhenxin Xingshui Yizhi Fang and its essential oil extract on cognitive deficits in mice.Method: For the purpose of this study 5 months old APP/PS1 double transgenic mice and wild-type C57BL/6JNju were selected as experimental animals.Then APP/PS1 double transgenic mice were randomly divided into model group,essential oil low and high-dose groups (12.13,48.50 mg·L-1),Zhenxin Xingshui Yizhi Fang group (0.46 g·kg-1).Meanwhile,wild-type C57BL/6JNju mice were used as a normal group.APP/PS1 double transgenic mice were treated with Zhenxin Xingshui Yizhi Fang and its essential oil extract for 22 consecutive days.Mice were subjected to a Morris water maze test and a platform test in order to determine their cognitive effect.Nissl's staining was used to observe pathological changes in brain tissue.Meanwhile,senile plaques (SP) were observed by employing Thioflavin-S staining.The expression of glucose transporter 1(GLUT1) and insulin receptor substrate-1(IRS-1) were analyzed using immunohistochemistry techniques.The levels of neurotransmitters such as acetylcholine (ACH),glutamate (GLU) and γ-aminobutyric acid (GABA) in the hippocampus were quantified by enzyme-linked immunosorbent assay (ELISA).Result: The memory function was significantly reduced in model group,and severe brain injury and neuronal apoptosis were also observed in comparison to normal group (PPPPPPPConclusion: These results indicate that Zhenxin Xingshui Yizhi Fang and its essential oil extract could ameliorate cognitive deficits and GLUT1 and IRS-1 could be a possible therapeutic target for AD.It may be an interesting approach to the treatment of Alzheimer's disease.

Finite element simulation of femoral neck fracture in osteoporotic rats / 医学研究生学报

Objective There are few reports on the establishment of the finite element model of the rat femur in China, and even none on the finite element analysis of rat hip fracture. This study aimed to build a finite element model of osteoporotic rat proximal femoral fracture base on fracture mechanics. Methods We collected the CT imaging data on the femur of a healthy adult SD rat and established a preliminary three-dimensional finite element model of the rat femur. We also constructed a finite element model of femoral neck fracture in an osteoporotic rat by mesh generation, defining the material properties, setting interfacial properties and failure parameters, and loading. Then we measured the crack moment, von Mises, shear stress, stress, strains, displacement, and the starting point of fracture. Results The von Mises of stress showed that the crack moment was 0.109980s and the maximum stress and shear stress were mainly distributed on the medial inferior and lateral superior of the femoral neck when damage started, with the maximum stress of 367.9 Mpa and the maximum shear stress of 200.4 Mpa. The maximum strains was 1.2%, which was consistent with the routes of crack extension and extended from the medial inferior to the superior. The maximum displacement was 1.6 mm, mainly distributed on the proximal femoral, concentrated at the femoral head, and a displaced femoral neck model was simulated finally. Conclusion The finite element simulation model of femoral neck fracture in osteoporotic rats was successfully established, which can provide a new method for biomechanical studies in animal experiments.

Inductive effect of solamargine on the apoptosis of human esophageal cancer KYSE150 cells and its action mechanism / 医学研究生学报

Objective Solamargine (SM), with its anti-inflammatory and anti-tumor effects, inhibits the proliferation and promotes the apoptosis of various tumor cells. This study was to investigate the effects of SM on the proliferation and apoptosis of human esophageal cancer KYSE150 cells and its action mechanism. Methods We treated KYSE150 cells with SM at the concentrations of 0 (the blank control group), 2, 4, 6 and 8 μmol/L for 24 hours. Then, we observed the morphological changes of the cells under the inverted microscope, detected their proliferation and apoptosis by MTT assay and flow cytometry respectively, and determined the expressions of the classical NF-κB signaling pathway-related proteins NF-κB, p-NF-κB, IKKα, IKKβ, IkBα and p-IkBα) and apoptosis-related proteins Bax, caspase-3, cleaved caspase-3 and Bcl-2 in different groups of the cells by Western blot. Results Compared with the blank control, the inhibition rate of the proliferation of the KYSE150 cells in the 2, 4, 6 and 8 μmol/L SM groups was increased significantly in a concentration-dependent manner (0 vs [15.03 ± 0.15]%, [47.94 ± 1.74]%, [68.72 ± 0.47]% and [77.51 ± 1.70]%, P<0.05), and so was the apoptosis rate ([8.17 ± 0.51]% vs [14.50 ± 0.73]%, [18.57 ± 2.08]%, [65.10 ± 10.88]% and [81.55 ± 5.48]%, P<0.05). The expression of the apoptosis-related protein Bax in the SM treated cells was up-regulated, those of Bcl-2, IKKα, IKKβ and p-IkBα down-regulated, and the activity of caspase-3 and cleaved caspase-3 promoted, all in a concentration-dependent manner, with statistically significant differences between the blank control and the 4, 6 and 8 μmol/L SM groups (P<0.05). Statistically significant differences were also found in the expressions of NF-κB, p-NF-κB and IkBα between the blank control and the 6 and 8 μmol/L SM groups (P<0.05). Conclusion Solamargine can significantly inhibit the proliferation and promote the apoptosis of KYSE150 cells, probably by suppressing the classical NF-κB signaling pathway.

Research on the mechanism of gut microbiota in reducing blood glucose of db/db diabetic mice by broad-spectrum antibiotics / 医学研究生学报

Objective The alterations of gut microbiota is closely related to metabolic diseases. The aim of this study was to analyze the effects of antibiotics on glucose metabolism and gut microbiota in mice, and to further explore the mechanism of gut microbiota in reducing blood glucose in db/db diabetic mice by broad-spectrum antibiotics. Methods 16 C57BL/KsJ-db/db mice were randomly divided into antibiotic group and control group with 8 mice in each group. Antibiotic group: broad-spectrum antibiotics(vancomycin 10mg/(kg·d), carbenicillin 50mg/(kg·d), metronidazole 50mg/(kg·d), neomycin 30mg/(kg·d)); Control group: 1% cellulose sodium solution as placebo treatment. Fasting blood glucose and body weights were recorded once a week during the study. At the same time, feces were collected for 16S rDNA gene sequencing analysis. The changes of fasting blood glucose, body weight, the relative abundance of microbiota, Shannon index, Simpson index and GLP-1 were compared between the two groups. Results After 5 weeks of treatment with broad-spectrum antibiotics (Vancomycin , Carbenicillin , Metronidazole , and Neomycin ), fasting blood glucose levels in db/db diabetic mice were significantly decreased (9.59±4.49mmol/L vs 19.71±8.74mmol/L,P=0.016). At the same time, antibiotics can also affect the gut microbiota of mice. The relative abundance of Proteobacteria in mice treated with antibiotics was significantly higher than that in control group (0.471±0.12 vs 0.177±0.12, P<0.05), and the OTUs of Proteobacteria, Enterobacteriaceae, Gamma-proteobacteria, and Enterobacteriales increased in mice treated with antibiotics compared with controls. In addition, we also showed antibiotics could change the diversity of gut microbiota, and the diversity of gut microbiota in antibiotic treated mice decreased significantly (Shannon index 3.135 vs 5.359, P<0.01); Simpson index 0.794 vs 0.946, P<0.01). Conclusion Broad-spectrum antibiotics can significantly reduce the fasting blood glucose level and the diversity of gut microbiota of db / db diabetic mice, and the alterations of gut microbiota may play an essential role in the process of reducing blood glucose by broad-spectrum antibiotics.