Objective To observe the hypoglycemic effect of total flavonoids from mulberry tree leaf (MTF) on diabetic rats and the effect of MTF on disaccharidases from rats. Methods Diabetic rats were treated with MTF, and then the change of blood glucose of these rats was observed; the brush border membrane from the small intestine of rats was stripped and homogenized, which was incubated with MTF and disaccharides, and the inhibitory rate of MTF on disaccharidases was determined. Blood samples from portal and peripheral veins were separately collected at 30, 60, 120 min after maltose solution was infused into small intestine in vivo, then the difference of blood glucose concentration between portal and peripheral veins was determined. Results MTF exerted a hypoglycemic effect on diabetic rats by inhibition of disaccharidases, the inhibitory rate of sucrase, maltase and lactase was 68.0%, 47.1%, 27.8% respectively, the difference of blood glucose concentration between portal and peripheral veins was also reduced. Conclusion The hypoglycemic effect of MTF on diabetic rats is probably via the inhibitory effect on small intestine disaccharidases in rats.

Objective:This study aimed to explore the effects ofnesfatin-1 on gastric distension (GD)-sensitive neurons in the basomedial amygdala (BMA) and the potential mechanism for nesfatin-1 to regulate gastric motility through the arcuate nucleus (Arc).Methods:The projection of nerve fiber and expression of nesfatin-1 were observed by retrograde tracing and fluo-immunohistochemistry staining;The nuclei microinjection and nuclei electrical stimulation,extracellular discharges of single unit neuron were used to observe the effects ofnesfatin-1 on the GD neurons;Gastric motility recording in vivo were used to monitor the effects ofnesfatin-1 on the amplitude of constriction and frequency of gastric motility in conscious rats.Results:NUCB2/Nesfatin-1/fluorogold-double labeled neurons were from ARC to BMA;Nesfatin-1 could excited the firing rate of most of the GD-E neurons (4.25± 1.02 Hz vs.5.32± 1.17 Hz,P＜0.01) and decreased the firing rate of most of the GD-I neurons (3.73± 0.92 Hz vs.2.64± 0.86 Hz,P＜0.01),inhibited the gastric motility,amplitude and frequency,SHU9119 could weaken the responses induced by nesfaton-1;Electrical stimulation of the Arc,the firing rate of nesfatin-1-induced GD-response neurons (GD-E:5.14± 1.32 Hz vs.6.75± 1.84 Hz,P＜0.05;GD-I:2.84± 0.86 Hz vs.4.05± 1.12 Hz,P ＜0.05) and the gastric amplitude and frequency were increase.Conclusion:It was suggested that nesfatin-1 in the BMA plays an important role in decreasing gastric motility and the Arc may be involved in this regulation process.

Objective:This study aimed to explore the Ventromedial Hypothalamic Orexin-1 and Orexin-1 Receptors in Regulation of Gastric Acid Secretion in Conscious Rats.Methods:Rats were anaesthetized and fitted with a stainless steel carmula placed just above the VMH or paracele,after random allocation orexin-A,[Pro34]-peptide YY and [CPP1-7,NPY19-23,Ala31,Aib32,Gln34] -pancreatic polypeptide were injected in the VMH;SB-334867 was intraperitoneal injection;atropine was subcutaneous injection;GR-231118 and CGP-71683 were injected in the paracele.Using pyloric ligation model,tests the effect of different drugs on rat gastric acid secretion and gastric juice volume.Results:OXA induced dose-dependent increase of gastric acid secretion;SB-334867 induced dose-dependent inhibition of gastric acid secretion.The stimulatory effect of OXA on acid secretion was inhibited by SB-334867;atropine induced dose-dependent increase of gastric acid secretion and block the effect of orexin-A on gastric acid secretion;the gastric acid secretion was inhibited by GR-231118 or CGP-71683,and GR-231118 or CGP-71683 were blocked the effect of orexin-A on gastric acid secretion;Intraventromedial hypothalamic injections of [CPP1-7,NPY19-23,Ala31,Aib32,Gln34]-pancreatic polypeptide increased gastric acid secretion.Conclusion:It is suggested that endogenous orexin-A acts on the ventromedial hypothalamus to stimulates acid secretion.This stimulatory effect is probably mediated through orexin receptor,Y1 and Y5 receptor,and the vagus nerve system.

Objective To investigate the correlation between posterior neck pain and lumbar epidural pressure (LEP)during percutaneous endoscopic lumbar discectomy (PELD).Methods A prospective study was performed on 86 patients undergoing PELD,46 males,40 females,aged 1 9-71 years,with ASA physical status of Ⅰ or Ⅱ.Each patient received lumbar epidural anesthesia.Lum-bar epidural pressure (LEP)was monitored continuously through a lumbar epidural catheter which was connected to a pressure transducer.LEP before the operation (LEPbase ),LEP at the time of pos-terior neck pain (LEPpain )and maximal LEP (LEPmax )were recorded.Results Thirty patients (34.9%)complained of posterior neck pain during the procedure.The lowest LEPmax was 31.0 mm Hg,and the highest LEPmax was 77.0 mm Hg.The LEPmax in patients with neck pain [(60.6± 8.8)mm Hg]was significantly higher than LEPmax in patients without neck pain [(50.7 ± 9.5 ) mm Hg](P <0.01 ).Patients with higher LEPmax had higher probabilities of having posterior neck pain (P <0.01).Conclusion Patients with higher LEPmax had higher probabilities of having posterior neck pain.

At present, many drugs were developed based on the main pathological feature of Alzheimer′s disease (AD): "β-amyloid cascade hypothesis and abnormal tau protein aggregation" as targets, but the efficacy is unsatisfactory. With the progress on the study of pathological mechanism of AD, the role of microglia and their related expression genes, such as TREM2, CD 33, ABCA7 gene and their related signal transduction pathways in the pathological mechanism of AD has been paid more and more attention. The study on AD biomarkers and therapeutic targets based on microglia and their related expression genes has also increased significantly. This review will mainly focus on the pathophysiology of microglia, the mechanism of microglia in AD, the biomarkers related to microglia and the drug treatment of AD.

This article devotes itself to evaluating the biocompatibility of synthetic macromolecular resin class of Comfort denture adhesive, which was developed by the present authors. Acute toxicity, haemolysis, cytotoxicity, sensitization and oral mucous stimulation were tested with standard method (ISO7406-1997 and YY0268-1995). The results showed that no toxic effect was observed with in vivo tests and no cytotoxic effect was observed with in vitro MTT assay. Haemolysis rate of the material (2.95%) indicated good hemaocompatibility. No local mucous membrane irritation reaction was noted after the relevant tests. The developed Comfort denture adhesive exhibited good biocompatiblility.
Adhesives ; pharmacology ; Animals ; Cells, Cultured ; Denture Retention ; Denture, Complete ; Humans ; Materials Testing ; Mouth Mucosa ; drug effects ; physiology ; Rabbits ; Rats ; Resins, Synthetic ; pharmacology

Objective To investigate the effects of orexin-A on firing activity of gastric distensionsensitive (GD) neurons in the basomedial amygdala (BMA) and food intake in diet-indaced obese rats.Methods Healthy male Wistar rats were selected,and the diet-induced obesity (DIO) rat model and dietinduced resistant (DR) rat model were established by high-fat diet.The effects of orexin-A and an opioid receptor antagonist naloxone on BMA GD neurons were observed by recording the extracellular potentials of single neurons.The effects of orexin-A and naloxone on the food intake of different rats were observed by using BMA catheterization.The mRNA expression and protein expression of orexin-1 receptor (OX-1R) and μ opioid receptor were detected by real-time PCR and Elisa,respectively.Results After microinjection of orexinA into the BMA,the firing frequency of GD-sensitive neurons in the normal rats was significantly increased (GD-E:(78.3±6.9)％,GD-Ⅰ:(55.5±4.7) ％,P＜0.01),and this effect was completely blocked by OX-1R receptor antagonist SB334867,and naloxone partially blocked the discharge-promoting effect of orexin-A;Compared with the normal rats,the firing frequency of GD-sensitive neurons in the DIO (GD-E:(91.6±7.1) ％,GD-Ⅰ:(67.9±8.1) ％) and DR(GD-E:(87.9±6.8) ％,GD-Ⅰ:(69.2±5.8) ％) rats was significantly increased after BMA injection of orexin-A (P＜0.05).After administration of orexin-A into the BMA,food intake of the normal rats,DIO rats and DR rats ((2.38±0.34) g,(3.75 ±0.32) g,(4.01 ±0.38) g,respectively) was significantly increased (P＜0.01),and the food intake of DR and DIO rats were significantly higher than that of normal rats (P＜0.05).After BMA was injected with naloxone,the food intake of rats was inhibited,and the food intake of the DIO rats was significantly lower than that of the DR rats (P＜0.05),food intake of the DR rats was significantly lower than that of the normal rats (P＜0.05).The results of real-time PCR showed that the mRNA levels of OX-1R in DIO and DR rats were(5.85±0.45)and (6.03±0.42)were higher than that of normal rats,and the difference was significant (P＜0.05);and mRNA levels of μ-opioid receptors in DIO and DR rats((4.51±0.42) and (8.31±0.41) times) were higher than those in normal rats (P＜0.05).The results of Elisa showed that the protein levels of OX-1R in DIO ((2.98±0.28) ng/μl)and DR rats ((3.05±0.31) ng/μl) were higher than those in normal rats ((1.53±0.31) ng/μl,P＜0.05).The content of μ-opioid receptor protein in DR rats ((4.21±0.35) ng/μl) was higher than that of DIO rats ((2.77±0.27) ng/μl),and higher than that of normal rats((1.48±0.32) ng/μ),the difference was significant (P＜0.05).Conclusion BMA orexin-A promotes the spontaneous discharge of GD-sensitive neurons and food intake in normal rats,DIO rats and DR rats,μ-opioid receptors may be involved in the regulation of this process.

Objective: To investigate whether γ-aminobutyric acid (GABA) receptor signaling pathway is involved in the regulation of thalamic undefined (ZI)-nucleus accumbens (NAc) neural pathways on gastric distraction (GD)-sensitive neuronal firing activity and the impact on food intake, the number of times and the frequency in rats. Methods: Six rats were randomly selected and the neural pathway between ZI and NAc in rat thalamus was observed by fluorescent gold (FG) retrograde tracing method.Eighty-two rats were randomly selected, and the gastric balloon was placed in gastric cavity, the microelectrode was placed in the NAc, and the stimulating electrode was placed in the ZI. The single-cell discharge recording method was used to observe the effect of electrical stimulation ZI on the excitability of GD-sensitive neurons in rat NAc.Eighteen rats were randomly selected and were divided into three groups according to the random number table. They were NS group, GABA group, GABA + GABA receptor antagonist bicuculline (BIC) group with 6 in each group, and the rat NAc was used to embed the cannula. The method of GABA and BIC was injected to observe the changes of cumulative food intake in rats for 4 h. Eighteen rats were randomly selected and randomly divided into three groups: sham stimulation (SS) group, 50 μA electrical stimulation group, 50 μA electrical stimulation + BIC group with 6 in each group. The 4 h cumulative food intake of rats was observed by electro-stimulation of rat ZI and rat NAc injection of BIC. Results: Fluorescent gold retrograde tracking combined with fluorescent immunohistochemical staining showed that there were visible GABA and fluorescent gold double labeled neurons in ZI. Electrical stimulation of ZI, the frequency of GABA-sensitive GD neurons in rat NAc increased significantly (GD-E increase: (78.8±8.4)%, GD-I increase: (89.3±9.2)%, P<0.01), but the inhibitory effect was antagonized by BIC (GD-E increase: (113.8±13.6)%, GD-I increase: (121.8±14.2)%, P<0.01). Microinjection of GABA in rat NAc significantly increased the cumulative food intake for 4 h ((155.72±18.84) kcal, t=3.41, P<0.05), which was antagonized by partial BIC (123.43±15.11) kcal, t=3.28, P<0.05). Electrical stimulation of ZI significantly increased the food intake in rats ((39.07±11.27) kcal, t=2.96, P<0.05), and this effect can be partially antagonized by BIC ((34.17±10.85)kcal, t=2.33, P<0.05). Conclusion The ZI-NAc neural pathway regulates the discharge activity of rat gastric distension (GD)-sensitive neurons and the feeding status of rats, and the GABA receptor signaling pathway may be involved in mediating the process.

Objective:To explore the effects and possible mechanisms of Tyrobp gene on neuroinflammation in Tourette's syndrome mice.Methods:Twenty C57BL/ 6J and Tyrobp knock-out male mice aged 6 weeks were randomly divided into 4 groups according to random number table method: WT+ NS group, Tyrobp -/-+ NS group, WT+ IDPN group and Tyrobp -/-+ IDPN group. Mice in WT+ IDPN group and Tyrobp -/-+ IDPN group were injected with IDPN intraperitoneally at a dose of 150 mg/kg·d, while mice in WT+ NS group and Tyrobp -/-+ NS group were injected with equal volume of normal saline, once a day for 7 days. Then stereotypical behavior of mice were evaluated. Western blot was used to detect the levels of Tyrobp, TNF-α, IL-6, IL-1β, TLR4, Myd88, p-NF-κB p65 and p-IκBα in the striatum of mice. Immunofluorescence staining was used to observe the activation of microglia. Statistical analysis was performed using GraphPad Prism 8.0 software, and t-test was used for comparison between two groups. One-way ANOVA was used to compare the means of multiple samples, and LSD test was used for further pairwise comparison. Results:The results of behavior assessment showed that there were significant differences in the motor stereotypic behavior and categorical stereotypic behavior score( F=270.9, 379.7, P<0.01), and the scores in WT+ IDPN group were higher than those in Tyrobp -/-+ IDPN group (motor stereotypic behavior: (3.23±0.26), (2.13±0.21), t=9.02, P<0.05; categorical stereotypic behavior: (45.80±4.29), (26.60±3.48), t=12.00, P<0.05). Western blot results showed that there were significant differences in the protein expression level of TNF-α, IL-6, IL-1β, TLR4, Myd88, p-NF-κB p65 and p-IκBα ( F=29.07, 23.09, 39.36, 57.6, 52.55, 15.50, 40.48, all P<0.05), the level of those in WT + IDPN group was higher than those in WT+ NS group( t=8.31, 7.37, 8.13, 11.43, 10.47, 6.05, 9.96, all P<0.05), Tyrobp -/-+ IDPN group was higher than Tyrobp -/-+ NS group ( t=3.60, 3.00, 5.84, 4.81, 3.59, 2.26, 4.68, all P<0.05), and WT + IDPN group was higher than Tyrobp -/-+ IDPN group ( t=3.97, 3.93, 4.14, 6.40, 7.63, 3.45, 3.03, all P<0.05). Immunofluorescence showed that microglial cells in the striatum region of mice in WT+ IDPN group and Tyrobp -/-+ IDPN group were enlarged and microglial cells were activated, and the activation pattern of microglial cells in WT+ IDPN group was more obvious than that in Tyrobp -/-+ IDPN group. Conclusion:Tyrobp may be involved in the pathogenesis of Tourette's syndrome by promoting neuroinflammation mediated by TLR4/Myd88/NF-κB signaling pathway.

Objective:To investigate the effects of TYRO protein tyrosine-binding protein(TYROBP)on neuroinflammation and autophagy via the PI3K/AKT signaling pathway in a transgenic APP/ PS1 mouse model of AD. Methods:C57BL/6J, TYROBP-/- and APP/ PS1 transgenic male mice aged 15-month-old were randomly divided into 3 group: the C57BL/6J group, the TYROBP-/- group and the APP/ PS1 group, with 19 in each group.The eight-arm maze test and novel object recognition test were conducted to assess the learning and memory ability of mice.The activation of microglia and NLRP3 inflammasomes were assessed by immunofluorescence.The mRNA levels of TNF-α, IL-6 and IL-1β were measured by real-time PCR, and the protein expression levels of NLRP3, cleaved caspase-1, SQSTM1, LC3B, TYROBP, p-PI3K, PI3K, p-AKT and AKT were assayed by Western blot. Results:Compared with the C57BL/6J group, the learning and memory abilities were significantly decreased(all P<0.05), activated microglia and NLRP3 inflammasomes were increased(all P<0.05), the mRNA and protein expression levels of TNF-α, IL-6, and IL-1β were increased(all P<0.05)and the protein expression levels of LC3B-Ⅱ, SQSTM1, TYROBP, p-PI3K, p-AKT were increased(all P<0.05)in the APP/ PS1 group.Compared with C57BL/6J group, the protein expression levels of TNF-α, IL-6, IL-1β, LC3B Ⅱ, SQSTM1, p-PI3K and p-AKT were decreased(all P<0.05). Conclusions:TYROBP promotes the inflammatory response and inhibits autophagy possibly by activating the PI3K/AKT signaling pathway, thus participating in the occurrence and development of AD.