Mice ; Animals ; Spiral Ganglion/physiology* ; Cochlea/physiology* ; Neurons

The cochlear auditory epithelium contains two types of sound receptors, inner hair cells (IHCs) and outer hair cells (OHCs). Mouse models for labelling juvenile and adult IHCs or OHCs exist; however, labelling for embryonic and perinatal IHCs or OHCs are lacking. Here, we generated a new knock-in Fgf8^P2A-3×GFP/+ (Fgf8^GFP/+) strain, in which the expression of a series of three GFP fragments is controlled by endogenous Fgf8 cis-regulatory elements. After confirming that GFP expression accurately reflects the expression of Fgf8, we successfully obtained both embryonic and neonatal IHCs with high purity, highlighting the power of Fgf8^GFP/+. Furthermore, our fate-mapping analysis revealed, unexpectedly, that IHCs are also derived from inner ear progenitors expressing Insm1, which is currently regarded as an OHC marker. Thus, besides serving as a highly favorable tool for sorting early IHCs, Fgf8^GFP/+ will facilitate the isolation of pure early OHCs by excluding IHCs from the entire hair cell pool.
Animals ; Mice ; Hair Cells, Auditory, Inner ; Cochlea/metabolism* ; Hair Cells, Auditory, Outer/metabolism* ; Disease Models, Animal ; Fibroblast Growth Factor 8/metabolism*

Objective: To observe the cellular damage of low-dose combined exposure to Hg, Pb and Cd on hippocampal neurons in rat. Methods: SH-SY5Y cells were randomly divided into 8 groups by 2×2×2 factorial design: control group, Pb exposure group, Hg exposure group, Pb+Hg exposure group, Pb+Cd exposure group, Hg+Cd exposure group and Pb+Cd+Hg exposure group. And the cell viabilities were measured. On this basis, an animal model was established. Twenty eight-week-old SD pregnant rats were randomly divided into four groups by random number table, and five in each group: the control group(distilled water), 1-fold metal mixture exposure group (1×MM, poisoning solution containing mercury chloride 0.15 mg/L, lead acetate trihydrate 25 mg/L, cadmium chloride 7.5 mg/L), 5-fold metal mixture exposure group (5×MM, poisoning solution containing mercury chloride 0.75 mg/L, lead acetate trihydrate 125.00 mg/L, cadmium chloride 37.50 mg/L), 10-fold metal mixture exposure group (10×MM, poisoning solution containing mercury chloride 1.50 mg/L, lead acetate trihydrate 250.00 mg/L, cadmium chloride 75.00 mg/L). Pregnant rats drank water until delivery. Twenty male pups were selected and exposed to these metals through breast milk until weaned. The heavy metals dose of poisoning water was adjusted, and then the weaned rats were exposed to heavy metals via drinking poisoning water until adulthood (postnatal day 83). The blood samples and brain hippocampus samples were collected to observe the ultrastructural changes of hippocampus, and to determine the levels of Hg, Pb and Cd in blood. In addition, apoptosis rate and fluorescence intensity of reactive oxygen species and intracellular free calcium concentration ([Ca²⁺]_i) in hippocampal neurons were measured. Results: Cellular factorial design analysis showed that Hg+Pb+Cd (at no observed adverse effect level, 1.0, 0.5 and 0.1 μmol/L, respectively)had a interaction on cell viability after 48 or 72 hours of combined exposure (P<0.05). The results of ultrastructure showed that mitochondria decreased, ridges and matrixes gradually dissolved in rat hippocampal neurons of 5×MM group; nuclear chromatin aggregated, more ridges and matrixes dissolved and the mitochondria also decreased in rat hippocampal neurons of 10×MM group. The concentration of Hg, Pb and Cd in the blood of 1×MM group, 5×MM group and 10×MM group were higher than those in the control group, and the differences were statistically significant (P<0.001). There was no significant difference in apoptosis rate between the 1×MM group and the control group. The apoptosis rate of 5×MM group and 10×MM group was higher than that in the control group, and the differences were statistically significant (P<0.001). There was no statistically significant difference in the fluorescence intensity of reactive oxygen species in hippocampal neurons of the 1×MM group and the control group. The fluorescence intensity of reactive oxygen species in the 5×MM group and the 10×MM group was higher than that in the control group, the difference was statistically significant (P<0.05). There was no significant difference in the fluorescence intensity of [Ca²⁺]_i between the 1×MM group and the control group. The fluorescence intensity values of [Ca²⁺]_i in the 5×MM group and the 10×MM group were higher than the control group, the differences were statistically significant (P<0.001). Conclusion Low-level combined exposure to Hg, Pb, and Cd caused synergistic neurotoxic damage, and the process may be related to the changes of neuronal apoptosis, reactive oxide species, and [Ca²⁺]_i levels.

Objective To observe the long-term efficacy of human fibrin sealant (FS) in the treatment of proximal type Ⅰ endoleak after endovascular aneurysm repair (EVAR) in abdominal aortic aneurysm (AAA).Methods The clinical data of 104 AAA patients with proximal type Ⅰ endoleak receiving EVAR + FS in Changhai Hospital from 2003 to 2012 was retrospectively analyzed,among those 77 cases were with less than 15 mm proximal neck,21 cases with greater than 60 degrees proximal neck angulation,37 cases with severe calcification or thrombosis in proximal neck.After failure of conventional endoleak therapy FS was injected through AAA catheter and long-term efficacy was evaluated by CTA during the follow-up.Results Intra-sac pressure decreased significantly after FS injection.Three patients (2.9％)died perioperatively.Postoperative 1'-,3' and 5 year survival rate was 91.8％,80.6％ and 60.2％respectively.Maximum diameter of AAA decreased from (58.78 ± 13.41) mm to (52.6-± 12.2) mm.There was no FS injection related complications.Conclusion Intra-sac injection of FS is an effective,economical and safe method for treating post-EVAR endoleak,especially for AAA with relatively short and twisted aneurysm neck.

BACKGROUND AND PURPOSE: There is increasing recognition of the importance of stroke in females to both clinical and public health. The natural course of stroke is worse in females than in males, but the evidence regarding sex disparities in the responses to thrombolysis in stroke patents is still controversial. We compared outcomes after thrombolysis treatment between females and males. METHODS: Clinical trials reported in the Embase, PubMed, and Cochrane Library electronic databases up to March 13, 2017 were included in this analysis. Two reviewers independently extracted the data and conducted quality assessments. Statistical tests were performed to check for heterogeneity and publication bias. Sensitivity analysis was also performed to evaluate the stability of the conclusions. RESULTS: Sixteen reports involving 60,159 patients were available for analysis. The female patients were a 0.89-fold [95% confidence interval (CI)=0.87–0.90, p < 0.001], 0.89-fold (95% CI=0.87–0.91, p < 0.001), and 1.24-fold (95% CI=1.11–1.36, p < 0.001) more likely to obtain good, excellent, and poor functional outcomes, respectively, with no significant difference in the complications of symptomatic intracranial hemorrhage among the sexes [risk ratios (RR)=0.99, 95% CI=0.92–1.07, p=0.81] after thrombolysis treatment. In addition, the prevalence of a good functional outcome did not differ significantly between females and males in the intra-arterial thrombolysis (IAT) group (RR=1.05, 95% CI=0.85–1.29, p=0.67) in a subgroup analysis. CONCLUSIONS: This study has demonstrated that females often exhibit a worse outcome than males after intravenous thrombolysis (IVT), whereas no relevant sex differences were found in outcome or recanalization after IAT, with safety regarding hemorrhage complications from thrombolysis being the same for the sexes. However, IVT should not be withheld from female stroke patients solely based on their sex before the findings are confirmed in further large-scale research.
Female ; Hemorrhage ; Humans ; Intracranial Hemorrhages ; Male ; Population Characteristics ; Prevalence ; Public Health ; Publication Bias ; Sex Characteristics ; Stroke*

Objective To prepare a new type of magnetic fluorescent nanoparticles and characterize them and analyze their applications in the field of biology and medicine.Methods In this paper,magnetic fluorescent nanoparticles-Fe3O4@PEI@RN were prepared by chemical synthesis.The content of the main components of the prepared particles was measured.The particles' size was analyzed by dynamic light scattering analysis,the effect of pH on the fluorescence properties was measured by fluorescence analysis,and some common metal ions,proteins and DNA were investigated whether they would interfere the particles'properties.Results The content of Fe3O4@PEI@RN showed that the autom of Fe was 14.1 mg/mL,rhodamine B was 7.6 mg/mL and napH thalimide was 94.8 mg/mL.The dynamic light scattered that the average particle diameter of the magnetic fluorescent nanoparticles was 224 nm.Fluorescence analysis showed that the fluorescence ratio F of Fe3O4@PEI@RN at 532 nm and 574 nm were pH-sensitive with a pKa of 6.73.When the concentration of common metal ions was 5 × 10-6,they did not change their fluorescence determinations,and when the protein concentration was less than 14 mg/mL and the DNA concentration was less than 20 mg/mL,they did not interfere with their determinations.Conclusion A new type of magnetic fluorescent nanomaterials is successfully prepared.Its good fluorescence shows it has great potential in the field of biomedicine.

Objective To prepare a new type of magnetic fluorescent nanoparticles and characterize them and analyze their applications in the field of biology and medicine.Methods In this paper,magnetic fluorescent nanoparticles-Fe3O4@PEI@RN were prepared by chemical synthesis.The content of the main components of the prepared particles was measured.The particles' size was analyzed by dynamic light scattering analysis,the effect of pH on the fluorescence properties was measured by fluorescence analysis,and some common metal ions,proteins and DNA were investigated whether they would interfere the particles'properties.Results The content of Fe3O4@PEI@RN showed that the autom of Fe was 14.1 mg/mL,rhodamine B was 7.6 mg/mL and napH thalimide was 94.8 mg/mL.The dynamic light scattered that the average particle diameter of the magnetic fluorescent nanoparticles was 224 nm.Fluorescence analysis showed that the fluorescence ratio F of Fe3O4@PEI@RN at 532 nm and 574 nm were pH-sensitive with a pKa of 6.73.When the concentration of common metal ions was 5 × 10-6,they did not change their fluorescence determinations,and when the protein concentration was less than 14 mg/mL and the DNA concentration was less than 20 mg/mL,they did not interfere with their determinations.Conclusion A new type of magnetic fluorescent nanomaterials is successfully prepared.Its good fluorescence shows it has great potential in the field of biomedicine.

The aim of the present study was to investigate the effects and mechanisms of quercetin on plantar incision-induced matrix metalloproteinase (MMP)-9 and MMP-2 activity,microglia activation and the analgesic effect of quercetin on plantar incision surgery-treated mice.Postoperative pain model was mediated by plantar incision surgery and Von Frey Hairs was used to test the mechanical pain threshold.The activity of MMP-9 and MMP-2 in spinal cord was evaluated by gelatin zymography.The marker of microglia ionized calcium binding adapter molecule 1 (IBA-1),phosphorylated p38 mitogen-activated protein kinase (p-p38 MAPK) was detected by Western blot.Results showed that quercetin (20,40,80 mg/kg,ip) significantly inhibited plantar incisioninduced mechanical allodynia and suppressed the activity of MMP-9 and MMP-2 in the spinal cord.Moreover,quercetin also markedly inhibited plantar incision-induced up-regulation of IBA-1 and p-p38 in spinal cord.In conclusion,quercetin may alleviate postoperative pain by suppressing MMP-9 and MMP-2 activity in microglia.

Objective To explore liver protective effects of the stems and leaves and roots of Scutellariae Radix from different areas of Gansu Province;To discuss differences in liver protection of the stems and leaves and roots of Scutellariae Radix. Methods All Kunming mice were randomly divided into 11 groups:normal group, model group, positive control group, Scutellariae Radix root groups and Scutellariae Radix stem-leaf groups of Longxi, Minxian, Weiyuan, Zhangxian. The mice received gavage with relevant medicine once a day for 7 days. 2 hours after the last medication, the mice were given peritoneal injection with 0.1%CCl4 and olive oil to establish the models with liver injury. Hepatic index, the activity of serum ALT and AST, the levels of T-AOC in the liver tissue were calculated in 18 hours after establishing the models. Results Compared with the model group, hepatic index, the activity of serum ALT and AST in the mice of Scutellariae Radix root groups from difference producing areas decreased significantly (P<0.05);the levels of T-AOC in the liver tissue was raised notably (P<0.05). Compared with stem-leaf groups from the same producing area, hepatic index, the activity of ALT and AST in the mice of Scutellariae Radix root groups were remarkably lower than these of Scutellariae Radix stem-leaf groups (P<0.05);the levels of T-AOC in the liver tissue was evidently higher than that of Scutellariae Radix stem-leaf group (P<0.05). Conclusion Scutellariae Radix root water decoction can prevent and protect CCl4-induced acute liver injury to a certain degree, while Scutellariae Radix stem-leaf water decoction shows no significant protective effect on acute liver injury.

Objective To study the antitumor effects of Scutellaria Radix extracts on H22 transplanted tumor in mice and its possible mechanism.Methods The H22 transplanted mouse models were established by inoculating H22 to mice. 60 mice were randomly divided into model group, 5-Fu group, low-, medium- and high-dose Scutellaria Radix extracts groups, with 12 normal mice as control group. All administration groups received gavage with relevant medicine. And then the body weight change, tumor growth inhibitory rate, and spleen and thymus indexes were calculated;the T-AOC and activities of SOD, and MDA content in serum were detected by spectrophotometer;DNA damage of peripheral blood lymphocytes was observed by single cell gel electrophoresis.Results Medium- and high-dose Scutellaria Radix extracts can significantly inhibit the growth of transplanted tumor. Compared with 5-Fu group, medium- and high-dose Scutellaria Radix extracts groups notably increased the body weight, spleen and thymus indexes of mice, promoted T-AOC and activities of SOD, and decreased MDA content in serum, as well as notably reduced DNA damage of peripheral blood lymphocytes.Conclusion Scutellaria Radix extracts have obvious antitumor effects on H22 transplanted tumor in mice and the possible mechanisms may be due to lightening the damage of normal tissue and cell from tumor, enhancing immunologic function and improving antioxidant capability of H22 bearing mice.