Nanocrystals self-stabilized Pickering emulsion loaded with active components of Tongmai prescription: preparation, characterization and evaluation by Caco-2 cell model / 药学学报

It is of great significance to apply the nanocrystals self-stabilized Pickering emulsion (NSSPE) to traditional Chinese medicine (TCM) compounds, and to study the effect of NSSPE on the oral absorption of various components with different solubility and permeability. In the study, NSSPE of Tongmai prescription was prepared by the high pressure homogenization method with nanocrystals of main active components (puerarin, ferulic acid, salvianolic acid B and tanshinone IIA) of Tongmai prescription as solid particle stabilizers and a mixture of Ligusticum chuanxiong essential oil and Labrafil M 1944 CS as oil phase. The NSSPE had better physical stability than nanocrystals suspension and blank emulsion. The adsorption of nanocrystals on the surface of oil droplets was confirmed by scanning electron microscopy and fluorescence microscopy. The surface adsorption rates of puerarin, ferulic acid, salvianolic acid B and tanshinone ⅡA in NSSPE were 15.40% ± 3.19%, 15.39% ± 5.07%, 10.97% ± 3.70% and 31.51% ± 1.60%, respectively. When solid active components were prepared into nanocrystals suspension, the cellular uptake and transport across Caco-2 cells were increased significantly for puerarin and tanshinone IIA. The uptake rates of ferulic acid, ligustilide and tanshinone IIA in NSSPE were further increased compared with the physical mixture of nanocrystals suspension and oil, and the transports of ligustilide and tanshinone IIA were also significantly improved. The main absorption mechanisms of NSSPE were passive diffusion and caveolin-mediated endocytosis, which were determined mainly by the microstructure of NSSPE. In conclusion, NSSPE could be applied to complicated TCM. The "micro" and "nano" synergistic microstructure with drug nanocrystals adsorbed on the surface of micron-sized oil droplets could not only improve the physical stability of NSSPE, but also promote the absorption of various components in NSSPE, which made NSSPE a promising oral drug delivery system for TCM.

Construction and application of "Five-in-one" blended teaching model in the course of fundamental nursing / 中华医学教育探索杂志

Objective:To construct a "Five-in-one" blended teaching model in the course of fundamental nursing with ideological and political education as the core, integrated with online and offline, and complemented with theory and experiment, and to explore its application effect.Methods:Eight classes of nursing undergraduates in Batch 2019 were selected through convenience sampling method, and through random cluster sampling, Class 5 to 8 were divided into control group and Class 1 to 4 were divided into experimental group. The control group used the traditional teaching method, the experimental group used the "Five-in-one" mixed teaching model. After the course, the teaching effect was evaluated by the professional commitment scale, the recessive truancy scale for college students, the self-regulated learning ability scale and the examination results. SPSS 23.0 software was used for t test. Results:After teaching, the scores of professional commitment, self-adjustment in recessive truancy, autonomous learning ability and examination results of the experimental group were higher than those of the control group [(91.30±10.38) vs. (87.31±16.40), (23.30±4.50) vs. (21.23±4.51), (82.31±10.06) vs. (79.42±9.79), (72.31±10.13) vs. (70.14±9.67) and (87.93±4.60) vs. (86.50±4.67), respectively]. The scores of academic cognition, learning habit, classroom cognition and learning environment in recessive truancy of the experimental group were lower than those in control group, with statistical significance.Conclusion:The application of "Five-in-one" blended teaching model in the course of fundamental nursing can reduce students' recessive truancy and improve their professional commitment, autonomous learning ability and academic achievement.

Berberine exerts antidepressant-like effects via regulating miR-34a-synaptotagmin1/Bcl-2 axis / 中草药·英文版

Objective: Berberine, a cationic alkaloid first isolated in 1917, has been approved by the China Drug Administration for decades. Accumulating evidence demonstrated its antidepressant-like activities in vivo. Our previous study has shown that chronic stress leads to the upregulation of miR-34a in the hippocampus of mice. This study aims to evaluate the underlying miR-34a mediated mechanism of berberine in chronic stress-induced depression in mice. Methods: In the present study, mice were administered with berberine during chronic stress. Levels of miR-34a, dendritic density, mitochondrial morphology, and neurogenesis were assessed in the hippocampus. Subsequently, miR-34a agomir was used as a pharmacological intervention for the investigation of berberine. Results: The results showed that berberine reversed the decrease in sucrose preference and the increase in latency to feed without altering total food consumption. Furthermore, chronic stress-induced overexpression of miR-34a decreased synaptotagmin-1 and Bcl-2 levels, thereby impairing spinal morphology, mitochondria and neurogenesis. Berberine inhibited miR-34a expression, in turn restored synaptotagmin-1 and Bcl-2 levels, and thus improved spinal morphology, mitochondria and neurogenesis in the hippocampus. However, the improvements induced by berberine were totally blocked by the pretreatment of miR-34a agomir, which caused the elevation of miR-34a levels in the hippocampus. Conclusion: This finding demonstrated that miR-34a downregulation was involved in the antidepressant-like effects of berberine in mice exposed to chronic stress.

Synergistic effects of autophagy/mitophagy inhibitors and magnolol promote apoptosis and antitumor efficacy

Mitochondria as a signaling platform play crucial roles in deciding cell fate. Many classic anticancer agents are known to trigger cell death through induction of mitochondrial damage. Mitophagy, one selective autophagy, is the key mitochondrial quality control that effectively removes damaged mitochondria. However, the precise roles of mitophagy in tumorigenesis and anticancer agent treatment remain largely unclear. Here, we examined the functional implication of mitophagy in the anticancer properties of magnolol, a natural product isolated from herbal

Prevention and treatment of complications in the treatment of femoral shaft closed fracture with core drilling intramedullary nail / 中国骨伤

OBJECTIVE@#To summarize the complications of core drilling intramedullary nail in the treatment of femoral shaft closed fracture and explore the treatment strategy.@*METHODS@#From August 2014 to June 2018, a total of 215 patients with closed femoral shaft fractures were treated with closed reduction core drill intramedullary nail, including 129 males and 86 females, aged from 18 to 62 years, with an average of (44.2±10.6) years old. The time from injury to operation was 3 to 21 days. There were 102 cases of AO type A fracture, 82 cases of AO type B fracture and 31 cases of AO type C fracture. The time of operation, the amount of blood loss during operation, the duration of hospitalization, the time of fracture healing and the HSS score of knee joint function at the last follow-up were recorded. The observation of complications included:iatrogenic fracture, core drill broken, core drill twist, postoperative infection, and fracture nonunion.@*RESULTS@#The average operation time was (63.2± 15.6) min and intraoperative blood loss was (150.0±34.5) ml. All the incisions reached grade A healing. Patients were follow up for a mean of (18.5±3.2) months, the average hospital stay was (4.3±1.2) days, and the average fracture healing time was (5.6±2.3) months. At the final follow-up, the average HSS score of knee joint was 90.3±4.7. Related complications occurred in 37 cases (17.2%). The core drill related complications occurred in 13 cases (6.0%), including core drill broken in 5 cases (2.3%), core removal in 1 case and slotting in 4 cases;core drill twist in 8 cases (3.7%). After the core was cut, the core was removed. Similar complicationsof conventional intramedullary nail:iatrogenic fracture was performed in 12 cases (5.6%), including 10 cases of fracture end split and 2 cases of distal perimedullary fracture of intramedullary nail. The patients with cleavage at the fracture end were not treated after judging their stability, and the patients with fracture around the distal end of the intramedullary nail were fixed with auxiliary steel plate during operation;1 case(0.4%) with delayed infection after operation, debridement and external fixation was replaced and healed after bone transfer; fracture nonunion occurred in 11 cases (5.1%), of which 7 cases (3.3%) were hypertrophic nonunion and healed with additional plate. Atrophic nonunion occurred in 4 cases (1.9%), which healed after additional steel plate and bone graft.@*CONCLUSION@#Core drilling intramedullary nail is an effective method for the treatment of closed femoral shaft fracture, and the complications include core drill related complications and conventional intramedullary nail similar complications. Accurate preoperative evaluation, careful operation during operation and early postoperative symptomatic treatment can effectively reduce the occurrence of related complications.

Study on oral absorption mechanisms of puerarin in nanocrystals self-stabilized pickering emulsion / 中国中药杂志

Nanocrystals self-stabilized Pickering emulsion(NSSPE) is a new kind of emulsion where only nanocrystals of poorly soluble drugs are used as stabilizers. Our previous study showed that NSSPE with Ligusticum chuanxiong oil as the main oil phase can significantly promote oral absorption of puerarin. The present study aimed to explore its absorption mechanism in oral administration. The in vitro dissolution test was carried out to study the effect of NSSPE on release of puerarin. The effects and mechanism of NSSPE on uptake and transport of puerarin across Caco-2 cell were investigated. The results showed that the drug release rate of NSSPE was similar to that of nanocrystals, with their cumulative dissolution of puerarin not affected by pH of releasing mediums, both significantly higher than that of crude material. The uptake of puerarin in NSSPE was concentration-dependent and significantly higher than that of solution or surfactant stabilized emulsion. Genistein and indomethacin, inhibitors of lipid rafts/caveolin, could significantly reduce the uptake of puerarin in NSSPE. Compared with solution, NSSPE and surfactants stabilized emulsion obviously increased transport rate K_a and apparent permeability coefficient P_(app) of puerarin in AP → BL direction, but there was no significant difference in BL → AP direction. It could be inferred that there were both passive and active transport mechanisms, as well as lipid raft/caveolin mediated endocytosis for absorption of NSSPE. The promoted oral absorption of puerarin in NSSPE was mainly related to the existing nanocrystal form which could promote dissolution, puerarin as well as Ligusticum chuanxiong oil which could promote drug transmembrane transport and inhibit drug efflux. It is the unique structure and composition of the compound NSSPE that promoted the oral absorption of puerarin.

Effect of Early Weight-bearing on Appropriate Population with Intertrochanteric Fracture after Surgery / 中国康复理论与实践

Objective:To observe the effect of early weight-bearing on the appropriate population with intertrochanteric fracture after surgery. Methods:From April, 2017 to December, 2018, a total of 45 patients with Evans-Jensen type II intertrochanteric fracture and fracture reduction as positive medial cortex support (PMCS) after proximal femoral nail anti-rotation (PFNA) fixation were randomly divided into control group (n = 22) and experimental group (n = 23). Weight-bearing as tolerated (WBAT) was initiated from six weeks after surgery in the control group, and within 48 h after surgery in the experimental group. The frequency of WBAT in two groups increased gradually from three times a day for ten minutes a time to five times a day for 20 minutes a time until clinical healing of fracture. The length of stay, hospital cost, the fracture healing time and the complication incidence were compared between two groups, as well as the scores of Visual Analogue Scale (VAS) and Harris Hip Score at six weeks, three months and six months after surgery. Results:Compared with the control group, the length of stay was shorter (t = 3.716, P < 0.01), the hospital cost was lower, but no significant difference was found (t = 1.540, P > 0.05), and the fracture healing time was shorter (t = 6.248, P < 0.001) in the experimental group. The complication incidence was lower in the experimental group, but there was no significant difference (χ2= 2.198, P > 0.05). Six weeks, three months and six months after surgery, there was no significant difference in the score of VAS between two groups (t < 1.330, P > 0.05). The score of Harris Hip Score was significantly higher in the experimental group than in the control group six weeks after surgery (t = -5.115, P < 0.001), however, no significant difference was found in other time points (|t| < 1.799, P > 0.05). Conclusion:Early weight-bearing within 48 h after PFNA fixation for Evans-Jensen type II intertrochanteric fractures and reduction with PMCS could shorten the length of stay, shorten the bony healing time and promote early recovery of hip function.

Transfection of microRNA-21 mediating the biological behavior and cellular radiosensitivity of esophageal squamous carcinoma cells / 解剖学报

Objective To study the biological properties of microRNA (miRNA) -21 expression in esophageal squamous cell carcinoma. Methods MiRNA-21 sense expression vector, miRNA-21 empty vector and miRNA-21 inhibitor were transfected and detected by fluorescence Real-time PCR. The normal cells of esophageal squamous cell carcinoma TE-1 were used as the control group, and the transfection result were detected. The cell proliferation activity was detected by cell counting kit-8(CCK-8), and the apoptosis ability was detected by flow cytometry. The invasion ability and migration ability of TE-1 cells were observed by Transwell chamber and scratch test. Changes in the sensitivity of TE-1 cells to radiotherapy were observed by colony formation experiments. The data were analyzed using SPSS 19. 0 software. Results The result of Real-time PCR showed that the expression level of miRNA-21 in TE-1 cells was significantly decreased after transfected with miRNA-21 inhibitor (P<0. 05). Compared with the normal cell growth group, positive control group and negative control group, the proliferation of TE-1 cells was reduced and apoptosis was accelerated after transfection with miRNA-21 inhibitor (P<0. 05). In addition, the ability of cell invasion and migration in the experimental inhibition group was decreased. Clone formation assays showed that inhibition of miRNA-21 expression significantly increased the sensitivity of TE-1 cells to radiation. Conclusion Down-regulation of miRNA-21 reduces the proliferation, invasion, migration and sensitivity of radiotherapy in esophageal squamous cell carcinoma TE-1 cells, and is a potential target for the future treatment of esophageal cancer.

A new type of adjustable weight bearing rehabilitation brace for lower limbs in postoperative rehabilitation of proximal femoral nail anti-rotation / 中国骨伤

OBJECTIVE@#To study and analyze the clinical effect of the self-developed new adjustable weight-bearing rehabilitation brace in the rehabilitation of the femoral intertrochanteric fracture after the operation of PFNA.@*METHODS@#From July 2015 to June 2017, 62 patients with typeⅡ (Evans-Jensen classification) intertrochanteric fracture of femur were treated with PFNA internal fixation. There were 11 males and 19 females in the routine rehabilitation group, with an average age of (70.73± 6.09) years;17 males and 15 females in the brace rehabilitation group, with an average age of (71.25±6.60) years. Among them, the patients in the routine rehabilitation group recovered according to the routine method, and the patients in the support rehabilitation group used the self-developed new adjustable weight-bearing rehabilitation support of lower limbs to assist the early rehabilitation. The pain intensity(VAS score), weight-bearing of affected limb, clinical healing time of fracture, Harris score and complications were recorded and analyzed.@*RESULTS@#Nine patients lost their visit half a year later, the other 53 patients were followed up for 9 to 18 months. The VAS score at 1, 3, 6 months after operation of brace rehabilitation group was lower than that of routine rehabilitation group(<0.05). The weight bearing of the limbs in the rehabilitation group was significantly higher than that in the conventional rehabilitation group(<0.05), but the clinical healing time of fracture in the brace rehabilitation group was shorter than that in the routine rehabilitation group(<0.05). In addition, the Harris score of the postoperativebrace rehabilitation group was better than that of the conventional rehabilitation group(<0.05). The incidence of complications was lower than that of the conventional rehabilitation group(=0.048).@*CONCLUSION@#In the rehabilitation of Evans Jensen typeⅡintertrochanteric fracture after PFNA internal fixation, the new self-developed adjustable weight-bearing rehabilitation brace can significantly relieve postoperative pain, regulate and moderately increase the stress stimulation at the fracture end, so as to promote fracture healing, accelerate the recovery of hip joint function, reduce the incidence of complications, and its clinical effect is safe and reliable.

Research progress of Pickering emulsion drug delivery systems / 药学学报

Pickering emulsion is a new type of emulsion which is stabilized by the adsorption of solid particles on the interface of emulsion droplets. In recent years, its applications in pharmacy have attracted more and more attention because of its higher resistance to coalescence and better safety than traditional surfactant emulsions. The Pickering emulsion was first used for topical administration to reduce skin irritation of surfactants and promote transdermal absorption of drugs. Recently, new oral and injectable Pickering emulsions have also been reported, which can promote oral absorption of insoluble drugs, improve stability of drugs, control drug release, targeted-delivery drugs, and serve as the carrier for novel immunological adjuvants. All these studies show Pickering emulsion a promising drug delivery system. However, its development in pharmacy is still in its infancy. There are many factors influencing the preparation of Pickering emulsions. But there is no systematic analysis of these factors up to now. In this review, we gave an overview of Pickering emulsions from their application in pharmaceutical field, preparation and evaluation, focusing on the effects of solid particles, oil phase, preparation technology and interaction of various factors on the fabrication of Pickering emulsions. The challenges and future directions of this exciting and rapidly expanding research area were further commented on, in order to provide reference for the in-depth study of Pickering emulsion drug delivery systems.

Metal/Matrix Enhanced Time-of-Flight Secondary Ion Mass Spectrometry for Single Cell Lipids Analysis / 分析化学

The chemical components analysis of single cell is important for understanding of physiological processes such as cell growth, signal transduction and apoptosis.Time-of-flight secondary ion mass spectrometry ( ToF-SIMS) is a sensitive surface analysis technique with high spatial resolution and can be used for single cell and micro-area analysis.However, relatively low ioniZation yield of biomolecules limited its wide application in single cell analysis.Herein, we used metal substrate and matrix material to enhance the ioniZation yield of lipids.The signal intensity of the phosphatidylcholine PC (40:0) casted on the matrix/gold coated silicon substrate was 65 times higher than that on the silicon wafer.Signal enhancement of phosphatidylcholine PC (34:1) on the single cell surface cultured on matrix/gold coated silicon substrate was observed as well.Due to the influence of irregular topography and complex chemical environment of cell, the increase of lipids signal was smaller.Delayed extraction mode of ToF-SIMS overcame the effects of cell topography, leading to further enhancement of the signal intensity of lipids.Meanwhile, simultaneous high spatial resolution of chemical imaging and high mass resolution of the mass spectra of single cells were obtained.Our strategies provided new insights into the study of cell metabolism and cell-environment interactions.

Intestinal absorption of puerarin nanocrystalline self-stabilizing pickering emulsion in rats / 中国中药杂志

To study the intestinal absorption characteristics of drug's nanocrystalline self-stabilizing Pickering emulsion (NSSPE) in situ in rats. Rat single-pass intestinal perfusion model was established, and high performance liquid chromatography (HPLC) was used to detect the concentration of puerarin in rat intestinal perfusion solution, assay the absorption rate constant (Ka) and the intestinal apparent permeability coefficient (Papp) of NSSPE in duodenum, jejunum, ileum, and colon, which were compared with those of raw material, nanocrystal and normal emulsion, respectively. For NSSPE, the Ka and Papp values were in the following order: duodenum>jejunum>ileum (<0.05)>colon (<0.01). However, there was no obvious difference between jejunum and ileum. As compared with raw material, nanocrystal and normal emulsion, the Ka and Papp values of NSSPE in duodenum were significantly higher than those of other three preparations (<0.05); and the Ka and Papp values of NSSPE in jejunum and colon were significantly higher than those of raw material, nanocrystal and normal emulsion (<0.01); and the Ka and Papp of NSSPE in ileum were also higher than those of raw material and normal emulsion (<0.05), but had no obvious difference with nanocrystal. The results showed that NSSPE could significantly improve the absorption of puerarin in the intestine of rats.

Research progresses of the effective mechanism of pyroptosis and its related diseases / 医学研究生学报

Pyroptosis is a newly discovered form of programmed cell death, which has a close relationship with infectious diseases and spontaneous inflammatory disease and autoimmune disease.Gasdermin-D is the effector of pyroptosis.Inflammatory caspases cleave Gasdermin-D, break the structural autoinhibition and active the pore-forming activity of Gasdermin-D.Gasdermin-D-N domain is the active form of Gasdermin-D.Oligomerized Gasdermin-D-N domain forms membrane pores.Both pyroptosis and necroptosis can form pores.In this article, the progress of the research on pyroptosis, the involvement of Gasdermin-D in the molecular mechanism of pyroptosis, the distinguishment of pyroptosis from necroptosis and pyroptosis-related diseases are reviewed.

Stability optimization of puerarin nanocrystalline self-stabilizied Pickering emulsion by response surface methodology / 中国中药杂志

A new Pickering emulsion, puerarin nanocrystalline self-stabilized Pickering emulsion (Pu-NSSPE) was developed. Box-Behnken design was used for optimizing the preparation formulation of Pu-NSSPE to improve its stability, and the effects of concentration of puerarin, volume ratio of water to oil, and pH value of water phase on the stratification index of emulsion, droplet size and drug concentration in emulsion were investigated. Results showed that the optimized Pu-NSSPE could be prepared with the concentration of puerarin of 0.5%, the volume ratio of water to oil of 9∶1 and the pH of water of 9. The size of emulsion droplet of optimized Pu-NSSPE was (12.70±1.17) μm and the drug content was (4.49±0.21) g•L⁻¹. The above indexes had no significant changes within the storage of 6 months at room temperature, indicating good stability. Microstructure characterizations by scanning electron micrograph, confocal laser scanning microscope and fluorescence microscope showed that the optimized Pu-NSSPE had a stable core-shell structure of emulsion droplet formed by the adsorption of puerarin nanocrystallines at the surface of oil droplets, which may be the microstructure reason for the long stability of Pu-NSSPE.

Development of Biological Nanopore Technique in Non-gene Sequencing Application / 分析化学

Nanopore technique is a low-cost, ultrafast method for single-molecule level analysis without labels. Nanopore technique was first proposed more than 20 years ago and exhibited an excellent potential in DNA sequencing. So far, the commercial development of nanopore strand-sequencing as a portable device has been realized. Meanwhile, a remarkable number of studies have demonstrated that nanopore represents versatile single-molecule sensors for a wide range of molecule. Therefore, in this article we mainly review the use of nanopore technique based on the interface interactions between biological pore and the analytes such as protein/peptide to obtain kinetic and thermodynamic information at single-molecule level. And a large number of biological molecules and metal ions are quantitatively detected by nanopore analysis, allowing its development for the future biotechnologies and medicine applications. Besides, electrochemical detection system is crucial to nanopore technique. Therefore, we focus on advancements in relative software and ultralow current instrumentations with high-bandwidth.

Effects of drug-oil properties on fabrication of drug nanocrystalline self-stabilizied Pickering emulsions / 中国中药杂志

To investigate the effects of drug and oil properties on the formation and stability of drug nanocrystalline self-stabilizied Pickering emulsions (NSSPE). Three insoluble Chinese medicine components (puerarin, tanshinone ⅡA and ferulic acid) were selected as model drugs, and Capmul C8, Fabrafil M 1944 CS, isopropyl myristate, Pzechwan Lovage Rhizome oil, and olive oil were used as oil phase. NSSPEs were developed by high pressure homogenization method and were evaluated for their appearance, centrifugal stability, droplet size and drug content changes in emulsion layer after storing at room temperature for 14 d. Then the properties of the oil (surface tension and viscosity) and properties of the drugs (surface energy, oil-water partition coefficient, size and Zeta potential of nanocrystalline and drug-water-oil contact angle) on the formation and stability of NSSPE were analyzed. The emulsification property and stability of five samples prepared with ferulic acid nanocrystals and different oils were significantly lower than those of puerarin and tanshinone ⅡA; the particle size of ferulic acid nanocrystals was 3.90 μm, extremely higher than 305 nm of puerarin and 406 nm of tanshinone ⅡA (P<0.05); the zeta potential of ferulic acid nanocrystals was -0.018 0 mV, significantly lower than －29.1 mV of puerarin and -42.6 mV of tanshinone ⅡA (P<0.05). Three samples prepared with isopropyl myristate and different drugs were not emulsions and the viscosity of isopropyl myristate was 4.67 mPa•s, significantly lower than that of the other oils (P<0.01). Puerarin-NSSPEs prepared with Pzechwan Lovage Rhizome oil showed best emulsification property and stability; the contact angle of puerarin in Pzechwan Lovage Rhizome oil-water was 69.7°, close to 90°, significantly higher than other contact angles. NSSPEs made by tanshinone ⅡA-Capmul C8-water, tanshinone ⅡA-Labrafil M 1944 CS-water showed highest stability, with a contact angle of 99.2° and 112° respectively, more close to 90° than other oils. The results indicated that viscosity, size and Zeta potential of nanocrystalline and three-phase contact angle had great influence on the formation and stability of NSSPE; surface tension of oil, surface energy of drug and oil-water partition coefficient may not be related to the construction of NSSPE.

The structure-activity relationships of novel α7 nicotinic acetylcholine receptor agonists based on indolizine scaffold / 药学学报

Alpha7 nicotinic acetylcholine receptor (α7 nAChR) is a ligand-gated ion channel critical for cognition, learning and memory. Deficiency of neuronal α7 nAChR has been implicated in the cognitive deficits and neuropsychiatric disorders. Chemical activation of α7 nAChR improves neurological functions in animal models. In this study, we designed and synthesized a series of indolizine derivatives with various substitutions at different positions on the scaffold, and investigated their structure-activity relationships (SAR). All compounds were screened and evaluated for their agonist activity using the two-electrode voltage clamp recording system in Xenopus oocytes expressing human α7 nAChR. Compound 16c carrying 6-methylindolizine moiety activates α7 nAChR with EC50 at 1.60±0.19 μmol·L-1 and maximum effect (Emax) of 69.0%±2.8% compared with 3 mmol·L-1 ACh. Compound 17b with 8-cyclopropyl substitution shows an increased Emax of 81.1%±9.3% with EC50 at 2.74±0.74 μmol·L-1. The SAR of the series shows that introducing the small hydrophobic groups at 6- or 8- position can improve both potency and maximum effect.

Preparation and evaluation of silybin nanocrystallines self-stabilizing Pickering emulsion / 药学学报

A new silybin nanocrystallines self-stabilizing Pickering emulsion (SN-SSPE) was developed using the high pressure homogenization method to improve the oral bioavailability of silybin. The influences of homogenization pressure from 50 to 120 MPa and drug content from 100 mg to 1000 mg on the formation of SN-SSPE were studied. The morphology, structure and size of emulsion droplet in SN-SSPE were characterized using scanning electron micrograph and confocal laser scanning microscope. SN-SSPE was evaluated, including stability, in vitro release and in vivo oral bioavailability. The particle size of silybin nanocrystallines (SN-NC) was decreased as the pressure increased until 100 MPa. When the drug content reached 300 mg or above, stable SN-SSPE was formed from sufficient SN-NC covering surfaces of oil droplets completely. The emulsion droplet of SN-SSPE with the size of 27.3±3.1 μm showed a core-shell structure consisting of oil droplet as core and SN-NC as shell. SN-SSPE showed a high stability over 40 days. In vitro release rate of SN-SSPE was faster than silybin coarse powder and similar to silybin nanocrystallines suspension (SN-NCS). After intragastric administration in rats, the peak concentration of SN-SSPE was increased by 2.5-fold and 2.3-fold compared with SN-NCS and silybin coarse powder, respectively. The AUC of SN-SSPE was increased by 1.4-fold and 3.8-fold compared with SN-NCS and silybin coarse powder, respectively. All these results showed that nanocrystallines of the poorly soluble drug could stabilize Pickering emulsions, which provides a promising application to the improvement of the oral bioavailability of poorly soluble drugs.

Relationship between vitamin D deficiency and early-onset neonatal sepsis / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To evaluate the effect of vitamin D level on early-onset sepsis (EOS) in neonates.</p><p><b>METHODS</b>Seventy-eight full-term neonates with EOS were used as the research group (EOS group). sixty healthy full-term neonates without clinical and/or laboratory features related to infections were used as the control group. Blood samples of the neonates and their mothers in both groups were collected within 72 hours of delivery to determine 25-hydroxyvitamin D(25-OHD) levels. The rate of vitamin D deficiency in the neonates and the level of 25-OHD supplemented to their mothers during pregnancy were compared between the two groups.</p><p><b>RESULTS</b>There was a significant positive correlation between the serum level of 25-OHD of the mothers and that of the neonates in both groups (EOS group: r=0.797, P<0.01; control group: r=0.929, P<0.01). The neonates and their mothers in the EOS group had significantly lower 25-OHD levels than those in the control group (P<0.01). The rate of vitamin D deficiency among the neonates in the EOS group was significantly higher than that of the control group (P<0.01). The level of vitamin D supplemented to the mothers during the last 3 months of pregnancy in the EOS group was significantly lower than that in the control group (P<0.01).</p><p><b>CONCLUSIONS</b>Low serum level of 25-OHD is associated with the development of early-onset sepsis in full-term neonates.</p>

The critical roles of mitophagy in cerebral ischemia

Mitochondria play a key role in various cell processes including ATP production, Ca homeostasis, reactive oxygen species (ROS) generation, and apoptosis. The selective removal of impaired mitochondria by autophagosome is known as mitophagy. Cerebral ischemia is a common form of stroke caused by insufficient blood supply to the brain. Emerging evidence suggests that mitophagy plays important roles in the pathophysiological process of cerebral ischemia. This review focuses on the relationship between ischemic brain injury and mitophagy. Based on the latest research, it describes how the signaling pathways of mitophagy appear to be involved in cerebral ischemia.