Ligustrazine-Loaded Borneol Liposome Alleviates Cerebral Ischemia-Reperfusion Injury in Rats.

Our team's pharmacological and clinical trials proved that ligustrazine/borneol spray had a definite effect on ischemic stroke (IS). To solve the shortcomings of ligustrazine/borneol spray, such as low bioavailability, short half-life, and poor compatibility between borneol and ligustrazine, ligustrazine-loaded borneol liposomes (LIP@TMP) were successfully prepared by a thin-film ultrasonication method. The average particle size of LIP@TMP was 282.4 ± 3.6 nm, the drug loading rate was 14.5 ± 0.6%, and the entrapment efficiency was 42.7 ± 1.0%, which had excellent stability and sustained release ability. In addition, live/dead fluorescent staining and the CCK-8 test confirmed that LIP@TMP had good biocompatibility. Moreover, middle cerebral artery occlusion (MCAO) rat model experiments further demonstrated that LIP@TMP could significantly alleviate cerebral ischemia and reperfusion injury by improving neurological scores, reducing cerebral infarct volume, promoting neurogenesis, inhibiting inflammation, and reducing tissue damage. In addition, LIP@TMP enhanced neuronal marker doublecortin (DCX) and neuronal nuclei (NEUN), inhibited inflammatory factors (TNF-α and IL-1ß), and reduced apoptosis signal molecules (TUNEL and caspase-3). The findings of this study suggested that the prepared LIP@TMP had tremendous potential for the treatment of cerebral ischemia.

Experimental Research on Variable Parameter Forming Process for Forming Specimen of TC4 Titanium Alloy by Selective Laser Melting.

To optimize the microstructure and properties of TC4 specimens formed by selective laser melting (SLM), the test program of formed specimens by the variable parameter forming process (VPFP) was designed based on the quantitative parameter forming process (QPFP). The purpose of this study is to explore the influence of the VPFP on the surface morphology, tensile properties, and microstructure of the specimens. The test results show that the surface morphology and tensile properties of the specimens were better formed by the VPFP. The internal holes of the specimens formed by the VPFP were small in volume and occupied a relatively small proportion, and the density could reach 99.7%. When the laser power was 300 W-260 W and equally divided into six hierarchies, the tensile strength could reach 1185.214 MPa by VPFP, but the elongation had no obvious change. The number of secondary acicular martensite α' phases was decreased in the microstructure of the specimens formed with VPFP. With the superposition of the hierarchy, the length of the primary acicular martensite α' phase became shorter, the width became larger, and the width of the columnar crystal ß phase became smaller. The VPFP is used to change the inherent method of forming specimens with the same parameters, which provides a new idea for SLM-forming structures; the test provides data and yields a theoretical research basis for forming the specimens process method.

Prediction of the Non-Isothermal Austenitization Kinetics of Fe-C-Cr Low Alloy Steels with Lamellar Pearlite Microstructure.

The austenitization of low alloy steels during rapid heating processes was involved in many kinds of advanced heat treatment technologies. Most of the previous research on the austenitization kinetics was focused on the spherical pearlite microstructures, which were different from the lamellar pearlite microstructures. In the present research, to predict the non-isothermal austenitization process of an Fe-C-Cr steel with lamellar pearlite, a novel 3-dimensional (3D) cellular automata model, which considered the influences of the coupling diffusion of Cr and C, and the interfacial diffusion between pearlite lamellae and the pearlite lamellar orientation, was established based on the thermodynamic equilibrium data obtained from the Thermo-Calc software and the simulation results of the DICTRA module. To clarify the influences of the heating rate on the austenitization kinetics and validate the simulation results, the austenitization processes of a Fe-1C-1.41Cr steel for different heating rates were studied with a series of dilatometric experiments. The good agreements between the cellular automata simulation results and the experimental results showed that the newly proposed cellular automata model is reasonable. The experimental results show an obvious change of the transition activity energies from the low to high heating rates. The transition from partitioning local equilibrium (PLE) to non-partitioning local equilibrium (NPLE) mechanisms was proved with DICTRA simulations. Basing on the simulation results, the influences of the pearlite lamellae orientation on the austenitization kinetics and the topological aspects of austenite grains were evaluated. In addition, the topological aspects of the rapidly austenitized grains were also compared to the normal grains.

Upregulation of the angiotensin-converting enzyme 2-angiotensin-(1-7)-Mas receptor axis by a combination of Yinyanghuo (Herba Epimedii Brevicornus) and Cheqianzi (Semen Plantaginis) improves erectile function in spontaneously hypertensive rats.

OBJECTIVE: To evaluate the effects of a combination of Yinyanghuo (Herba Epimedii Brevicornus) (HEB) and Cheqianzi (Semen Plantaginis) (SP) on erectile dysfunction caused by essential hypertension in spontaneously hypertensive rats (SHRs), and to elucidate the role of the angiotensin-converting enzyme 2-angiotensin-(1-7)-Mas receptor (ACE2/Ang [1-7]/Mas receptor) axis in this process. METHODS: A total of 24 SHRs were randomly assigned to three groups: SHR-control, low-dose (12.5 g/kg) and high-dose (25 g/kg) HEB+SP (HEBSP). Eight Wistar-Kyoto rats were used as normal controls. HEBSP was administered by oral gavage for 28 d. Erectile function was measured once a week using the Heaton test. After 4 weeks of treatment, the corpus cavernosum was harvested from each rat to measure nitric oxide (NO), nitric oxide synthase (eNOS) and Ang (1-7) levels, as well as ACE2, Mas receptor and neuronal nitric oxide synthase (nNOS) protein expression. RESULTS: After 4 weeks of treatment, HEBSP significantly increased erectile function in the treated group compared with SHR-control group (P < 0.01). Additionally, HEBSP treatment significantly increased cavernosal levels of Ang (1-7), eNOS and NO. Moreover, HEBSP significantly elevated the expression levels of ACE2, Mas receptor and nNOS. These beneficial effects were elevated in the high-dose HEBSP group. CONCLUSION: HEBSP improved erectile function in SHRs by upregulating the ACE2/Ang (1-7)/Mas receptor axis, eNOS and nNOS pathways.

Comparative quality of the forms of decoction pieces evaluated by multidimensional chemical analysis and chemometrics: Poria cocos, a pilot study.

Many Chinese medicinal materials (CMMs) are parts of plants or fungi that have been processed into different physical forms, termed decoction pieces, that are typically boiled in water for consumption. One CMM may have several decoction pieces forms, e.g., slices, small cubes (dice), or grains. The specifications that have different morphological parameters (shape, size and thickness) for these various decoction pieces have been developed over, in some cases, centuries of practice. Nevertheless, whether and how the form of decoction pieces affects the extraction (decoction) dynamics, and quality stability during storage has not been studied. Here, we investigated Poria cocos (PC) as a pilot study; we explore how the form of PC decoction pieces affects its chemistry using multidimensional chemical evaluation such as ultra-performance liquid chromatography-photodiode array-quadrupole time-of-flight mass spectrometry (UHPLC-PDA-QTOF-MS/MS), ultra-performance liquid chromatography-triple quadrupole mass spectrometry (UHPLC-QqQ-MS/MS) and high performance gel permeation chromatography coupled with charged aerosol detector (HPGPC-CAD), combined with analysis of variance (ANOVA), principal component analysis (PCA), factor analysis (FA) and hierarchical cluster analysis (HCA). The results indicated that different specifications had significant differences, and these specifications could be divided into four groups. The comprehensive results of the chemical analyses undertaken here indicate that the highest potentially available quality of PC decoction pieces was in the forms of curl, ultra-small grains and small grains, followed by thin slices. This information not only is conducive to promoting the standardization of the specification/form of PC decoction pieces and maximizing the benefits from its utilization, but also provide a promising strategy for assessing other CMM decoction pieces in different forms.

Conjugation of vitamin E-TPGS and guar gum to carry borneol for enhancing blood-brain barrier permeability.

Herb borneol is usually used in clinics for the treatment of central nervous system illness, for its ability of blood-brain barrier permeability, although its poor water solubility and poor bioavailability limit its clinical application to some degree. In this study, we developed a novel nanoparticle combining the benefits of vitamin E d-ɑ-tocopheryl poly(ethylene glycol) succinate (E-TPGS) (or TPGS) and guar gum to get TPGS-g-guar gum as a drug delivery system to carry borneol, which could improve the solubility of borneol and increase the drug-loading capacity efficiently. The results showed that TPGS-g-guar gum nanoparticles delivery system was suitable to carry borneol and release the drug effectively, and TPGS-g-guar gum/borneol nanoparticles would be a potential platform for improving the treatment of central nervous system illness and cerebrovascular disease.

Beam Diameter Dependence of Performance in Thick-Layer and High-Power Selective Laser Melting of Ti-6Al-4V.

A 400 W high-power laser was used to fabricate 200-µm-thick Ti-6Al-4V samples to evaluate the effects of small (50 µm) and large (200 µm) beam diameter on density, microstructure and mechanical properties. A series of single-track experiments demonstrated that it was challenging for the small-beam laser to fabricate smooth and defect-free scan tracks. A larger beam diameter efficiently avoided process instability and provided a more stable and uniform melt pool. By increasing the beam diameter, the density of multilayer samples reached 99.95% of the theoretical value, which is much higher than that achieved with the small beam diameter. However, it was difficult to completely eliminate defects due to serious spatter and evaporation. Moreover, all of the generated samples had relatively coarse surfaces. For the large beam diameter of 200 µm, the optimal yield strength, ultimate tensile strength and elongation were 1150 MPa, 1200 MPa and 8.02%, respectively. In comparison, the small beam diameter of 50 µm resulted in values of 1035 MPa, 1100 MPa and 5.91%, respectively. Overall, the large-diameter laser is more suitable for high-power selective laser melting (SLM) technology, especially for thick layers.

[Research of pollution-free and precision cultivation system of Chinese herbal medicines].

The issues of disordering production and non-standard pesticide application are common in the production of Chinese herbal medicines. Aimed to above problems, research groups built the pollution-free and precision cultivation system of medicinal plants. This system mainly included the precise site selection of medicinal plants based on the GIS technology, modern omics-assisted breeding, metagenomics guiding the soil complex improvement, and the precise field management based on rational application of fertilizer and comprehensive control of disease. At present, the production and distribution of medicinal plants were performed in the many poor counties of the whole nation. The breeding platform of resistant varieties was built, and certificates of new and well-bred varieties were received, in the base of genetic backgrounds of the original species of medicinal plants. The disease incidences were declined after application of these resistant varieties. Additionally, chemical pesticide consumption of medicinal plants (such as Panax ginseng, P. notoginseng, Salvia miltiorrhiza, P. quinquefolium, Schisandra chinensis, Platycodon grandiflorum and P. grandiflorus etc.) reduced by 20%-80% based on the genetic testing technologies of plant diseases and insect pests and safety evaluation of pollution-free pesticides. The application of pollution-free and precision cultivation system of Chinese herbal medicines achieve significantly social, economic and ecological benefits.

Research on High Layer Thickness Fabricated of 316L by Selective Laser Melting.

Selective laser melting (SLM) is a potential additive manufacturing (AM) technology. However, the application of SLM was confined due to low efficiency. To improve efficiency, SLM fabrication with a high layer thickness and fine powder was systematically researched, and the void areas and hollow powders can be reduced by using fine powder. Single-track experiments were used to narrow down process parameter windows. Multi-layer fabrication relative density can be reached 99.99% at the exposure time-point distance-hatch space of 120 µs-40 µm-240 µm. Also, the building rate can be up to 12 mm³/s, which is about 3-10 times higher than the previous studies. Three typical defects were found by studying deeply, including the un-melted defect between the molten pools, the micro-pore defect within the molten pool, and the irregular distribution of the splashing phenomenon. Moreover, the microstructure is mostly equiaxed crystals and a small amount of columnar crystals. The averages of ultimate tensile strength, yield strength, and elongation are 625 MPa, 525 MPa, and 39.9%, respectively. As exposure time increased from 80 µs to 200 µs, the grain size is gradually grown up from 0.98 µm to 2.23 µm, the grain aspect ratio is close to 1, and the tensile properties are shown as a downward trend. The tensile properties of high layer thickness fabricated are not significantly different than those with a coarse-powder layer thickness of low in previous research.

Effect of Yinian Jiangya Yin on primary hypertension in early stage--a clinical observation on 40 patients.

OBJECTIVE: To observe the effect of Yinian Jiangya Yin (Decoction for lowering blood pressure to prolong life) on patients with early hypertension and its mechanism on the function of vascular endotheliocytes. METHODS: The 79 patients with early primary hypertension belonging to the TCM syndrome of stagnation of phlegm and blood stasis in meridians and hyperactivity of the liver-yang were randomly divided into a treatment group of 40 patients treated with Yinian Jiangya Yin and a control group of 39 patients treated with Tianma Gouteng Yin (Decoction of Gastrodia and Uncaria). The changes in score of TCM syndrome and in blood pressure before and after treatment were observed in the two groups. The contents of nitrogen monoxide (NO) and endothelin (ET) in serum after treatment were determined. RESULTS: There was a statistical difference (P < 0.05) in score of TCM syndrome, effect of lowering blood pressure, and the contents of ET and NO in serum after treatment between the two groups. CONCLUSION: The effect of Yinian Jiangya Yin on improving TCM syndrome of patients with primary hypertension in early stage and on lowering blood pressure may be related to its regulating the imbalanced condition between ET and NO for restoring the function of endothelium-dependent vasodilation.

[Effects of yinian jiangya decoction contained serum on endothelial cell proliferation and PPAR gamma mRNA expression in spontaneously hypertensive rat].

OBJECTIVE: To observe the effects of Yinian Jiangya (YNJY) Decoction contained serum on cell proliferation of primary cultured endothelial cells of spontaneously hypertensive rat (SHR) and the peroxisome proliferator-activated receptor-gamma (PPAR-gamma) mRNA expression in the cells. METHODS: SD rats were fed with high-lipid diet and different doses (high, medium and low, containing crude drug of 5.2 g/mL, 2.6 g/mL, 1.3 g/mL respectively) of YNJY respectively and the serum contained different doses of YNJY (S-YNJY) was prepared by collecting the rats' serum after 20 days of feeding. The serum obtained from SD rats fed with normal diet, i.e. drug free serum (S-free) was taken for control. Primary cultured endothelial cells of SHR were treated respectively with S-YNJY in different doses (treated groups) and S-free (control group), the cell activity and the mRNA expression of PPAR-gamma in cells of all groups were detected by MTT and RT-PCR respectively at different time points: 2, 4, 8, 16 and 24 h after treatment. RESULTS: MTT test showed that at time points of 4 and 8 h, the OD value raised in the treated groups with insignificant difference among them (P>0.05), but was higher than that in the control group (P<0.05); at 16 h, it increased but showed a smaller increment in the medium-dose treated group (P<0.05); at 24 h, it decreased in all groups, but the decrement in the high- and medium-dose treated groups was more remarkable (P<0.05); at 48 h, it decreased continuously, with the decrement more significant in the high-dose group than in the control group (P<0.05). RT-PCR detection showed that at 4 h, the expression of PPAR-gamma mRNA was not changed significantly in all groups (P>0.05); at 8 h, it was remarkably lower in high-dose group than in others (P<0.05); at 16 h, it was higher in the three treated groups than in the control group (P<0.05), with a highest level shown in the high-dose treated group (P<0.01); at 24 h, the expression decreased in all groups, but the level in the low-dose treated group was still higher than that in the control group (P<0.05). CONCLUSIONS: YNJY Decoction shows a two-way regulation on endothelial cells proliferation, and which is negatively dose-dependent in the late stage. The regulation is perhaps relevant to the regulating of the PPAR-gamma mRNA expressions. The PPAR-gamma mRNA expression up-regulating and maintaining effects of YNJY Decoction may be one of the mechanisms for its vascular endothelial cell protection and blood pressure suppressing.

[Intervention of Huanglian Jiedu decoction on haemorheology and cholesterol-supplemented diet].

OBJECTIVE: To study the influence of Chlamydia pneumonia (Cpn) infection on haemorheology and atherosclerosis and the intervention of Huanglian Jiedu decoction (HJT). METHOD: At the beginning of the experiment, all the sixty New-Zealand rabbits were token blood to test Cpn IgG and all the results were negative. Eight New-Zealand rabbits were randomized into normal group F, and all other rabbits were fed with forage containing 2.5 g x kg(-1) cholesterol and infected with Cpn via nasophrynx for three times during 6 weeks. At the end of the sixth week, forty-four rabbits with serum Cpn IgG positive were randomized into four groups: Group A treat with HJD 2 g x kg(-1) d(-1) by gastric gavage, group B with HJT 1 g x kg(-1) x d(-1), group C with azithromycin 20 mg x kg(-1) x d(-1), model group D with normal saline for six weeks. Group E was set up in eight rabbits with serum Cpn IgG negative and served as the control. At the end of 18th week, blood was token from middle ear artery to test haemorheology such as whole blood viscosity, plasma viscosity, haematocrit, erythrocyte aggregation index (EAI), erythrocyte rigidity index (IRI), and erythrocyte deformability index (EDI). After that, all the rabbits were executed and the pathological features of aorta tissue were observe under microscope. RESULT: Haemorheological disorder and atherosclerotic changes were obvious in both group D and E. while maximum intimal thickness (MIT) (23.65 +/- 8.19 vs 12.76 +/- 4.06), atherosclerotic damage percentage (P(LCI)) (41.08 +/- 12.51 vs 22.43 +/- 9.45), plaque area index (I(PA)) (9.57 +/- 1.82 vs 2.84 +/- 0.25) in group D was much higher than that in group E (all P < 0.01). Compare with group D, haemorphological disorder and atherosclerotic changes were much improved in group A, B and C. MIT (6.45 +/- 1.27 vs 23.65 +/- 8.19), (P < 0.01), P(LCI) (22.39 +/- 6.74 vs 41.08 +/- 12.51), (P < 0.05) and I(PA) (1.44 +/- 0.33 vs 9.57 +/- 1.82), (P < 0.01) in group A was much lower than that in group D. And MIT (12.65 +/- 3.63 vs 23.65 +/- 8.19), (P < 0.01) and I(PA) (4.43 +/- 1.17 vs 9.57 +/- 1.82), (P < 0.05) in gruoup B was much lower than that in group D too. CONCLUSION: Cpn infection could aggravate the haemorheology disorder in cholesterol-supplemented-diet rabbits, and both antidotal decoction of Coptis and azithromycin can alleviate it.

[Influence of borneol on nasal absorption of Ligustrazinee].

OBJECTIVE: To evaluate the influence of borneol on nasal absorption enhancement of ligustrazine. METHOD: The rats were randomly divided into 3 groups: Xiongbing nasal spray group (group A), Chuanxiong nasal spray group (group B) and Xiongbing group by decoction intragastric administration (group C). All the rats were decapitated at several time points after administration. The whole brains of rats were taken to homogenate and detected the concentrations of ligustrazine. RESULT: Compared with group B and C, group A has its characteristics: quick absorption, quick distribution and quick excretion of ligustrazine. CONCLUSION: Nasal administration is a quick-acting way for ischemic cerebral vessel insufficientia. Borneol promoted nasal absorption of ligustrazine into brain.