Objective To study the effect of hearing loss on language function and the mediating effect of de-pression on hearing loss and language function,to provide a reference for the intervention of language function im-pairment in the elderly.Methods Data of 6 002 older adults ≥65 years old from the Hubei Aging and Memory Co-hort Study(HAMCS)were collected from 2018 to 2022.A multivariate logistic regression model was used to ana-lyze the effect of hearing loss on language function,and a Bootstrap method was used to analyze the mediating effect of depression score on hearing loss on language function.Results Among 6 002 older adults ≥65 years old,1 137(18.94％)had mild hearing loss,264(4.40％)had moderate and severe hearing loss,and 2 611(43.50％)had language function impairment.After controlling for related factors such as age,years of education,marital status,place of residence,physical exercise,intellectual activity,hypertension,coronary heart disease and cerebrovascular disease,multivariate logistic regression analysis showed that the risk of speech function impairment in the elderly with mild hearing loss and moderate to severe hearing loss was 1.33 times(95％CI:1.13～1.56,P=0.001)and 1.77 times(95％CI:1.29～2.42,P＜0.001)respectively.The mediating effect showed that depression played a partial mediating role between hearing loss and language function,and the mediating effect was-0.021(95％CI:-0.027～-0.015,P＜0.001),accounting for 12.96％of the total effects.Conclusion Hearing loss increases the risk of language impairment,and depression playing a partial mediating role between hearing loss and language func-tion in the elderly.

Objective: To explore the therapeutic effects of ginseng total saponins (GTSs) on cognitive impairments in astronauts caused by prolonged exposure to microgravity environment. Methods: Fifty specific pathogen-free (SPF) male Wistar rats were randomized into control, hindlimb suspension (HLS), Huperzine A (HLS-Hup A 0.1 mg/kg), low-dose GTSs (HLS-GTSs 100 mg/kg), and high-dose GTSs (HLS-GTSs 200 mg/kg) groups, based on the completion time of reward-directed conditioning tasks. Except for rats in the control group, the others were subjected to HLS and treated with drugs (day 20 – 58), received reflex test under the condition of rewarding, and underwent Nissl body staining and Western blot detection on hippocampal. Results: After modeling, rats in HLS group exhibited a reduction in the number of lever presses and an increase in the completion time of the reward-directed operant conditioning task Ⅰ (P < 0.05) when compared with the control group, which were not substantially altered in the HLS-GTSs 100 and 200 mg/kg groups (P > 0.05). In the reward-directed operant conditioning task Ⅱ, the HLS group rats demonstrated a marked decrease in the number of lever presses (P < 0.05) and nose pokes (P < 0.01) when compared with the control group rats; the HLS-GTSs 100 mg/kg showed a significant increase in the number of lever presses and nose pokes (P < 0.05), while the HLS-GTSs 200 mg/kg demonstrated a significant reduction in completion time and an elevation in the number of lever presses (P < 0.05) when compared with the HLS group rats. In visual signal discrimination task, compared with the control group rats, the HLS group rats showed decrease in the indexes of the visual signal discrimination(P < 0.01), while HLS-GTSs 100 and 200 mg/kg groups exhibited manifest increase in it (P < 0.01). In reward extinction experiment, the number of lever presses in HLS rats significantly increased when compared with the control group (P < 0.01); compared with the HLS group, HLS-GTSs 100 and 200 mg/kg groups demonstrated a marked descrease (P < 0.05). The expressions of N-methyl-D-aspartic acid receptor 1 (NR1) and phosophorylated N-methyl-Daspartic acid receptor 2B (p-NR2B) proteins were markedly decreased in rats in the HLS group (P < 0.05 and P < 0.01, respectively), while that of NR2B protein maintained the same (P > 0.05). GTSs increased the expression levels of p-NR2B (P < 0.01). Conclusion GTSs improved the learning and memory ability of complex operations by regulating the NR1/NR2B phosphorylation pathways in rats.

Objective To study the characteristics of a rat model of migraine with hyperactivity of liver-yang and blood stagnation,which was established by Fuzi Decoction combined with electrical stimulation of the trigeminal ganglion.Methods The 30 SD rats were divided into normal group,model group,and Zhengtian pill group(1.6 g·kg-1),with 10 rats in each group.Rats in the model group and Zhengtian pill group were fed with aconite decoction(2.00 g·kg-1)once a day for 28 day to establish the hyperthermia model;On the 15 day of intragastric administration,rats in the Zhengtai pill group were simultaneously given Zhengtai pill solution once a day for 14 day;At 29 day,the trigeminal ganglion was stimulated to create the migraine model of hyperliver and stasis.After 30 min of the last dose,the macroscopic signs and behaviors were observed,and the blood rheology was detected by blood visticometer.Positive substance P(SP)expression,mRNA and relative protein expression in the trigeminal cervical pulp complex(TCC)in rat mice by immunohistochemistry,RT-qPCR and Western blot analysis.Results Compared with the normal group,the model group has macro signs such as red eyes,irritability,cage fighting,dark tongue and stasis points;regular head positioning and frequent hair management;increased distance in the central area(P<0.05).The relative viscosity of whole blood,plasma viscosity,red blood cell aggregation index all increased(P<0.05),and the red blood cell variant index decreased(P<0.05);SP positive expression,mRNA and the relative protein expression increased in TCC(P<0.05).Compared with model group,Zhengtian pill group can improve macro representation and behavior significantly;can significantly reduce central distance(P<0.05);can reduce plasma viscosity,high-shear relative viscosity of whole blood,and red blood cell aggregation index(P<0.05);increase the Red blood cell variant index significantly(P<0.05);down-regulate SP positive expression,mRNA and relative protein expression in TCC(P<0.05,P<0.01).Conclusion SD rats were used for 4 weeks to construct a migraine model of hyperhepatic hyperactivity and stasis,which was basically consistent with the clinical manifestations.

OBJECTIVE To expl ore the mechanism of effe ctive fractions from Xiongma decoction in the treatment of migraine with hyperactivity of liver-yang and blood stasis. METHODS Totally 70 male SD rats were randomly divided into normal group ， model group ，positive control group （Flunarizine hydrochloride capsules 0.9 mg/kg），low-dose and high-dose groups of Xiongma decoction effective fractions （ethyl acetate extract 0.87，3.46 g/kg，n-butanol extract 1.80，7.20 g/kg）. Except for normal group ， rats in other groups were given aconite decoction （2 g/kg），once a day ，for 4 consecutive weeks to establish the hyperactivity model of liver-yang. On the 15th day of modeling ，all administration groups were given corresponding drugs intragastrically at the same time ，once a day ，for 2 consecutive weeks. On the 29th day of modeling ，rats trigeminal ganglion was stimulated to establish the migraine model with hyperactivity of liver-yang and blood stasis ，then the medication was maintained for another time according to the above method. The macroscopic signs and behavior of the rats were observed ；positive expression ，mRNA and protein expression of transient receptor potential vanilloid 1 （TRPV1），calcitonin generelated peptide （CGRP），calcitonin receptor-like receptor （CRLR） and receptor-associated membrane proteins 1 （RAMP1） in trigeminal cervical spinal complex （TCC） were detected by immunohistochemistry ，RT-qPCR and Western blot assay. RESULTS Rats in model group showed macrophysical signs and behaviora l manifestations related to migraine with hyperactivity of liver-yang and blood stasis. Thirty minutes after last administration ，the above conditions of rats in Xiongma decoction effective fraction groups were improved significantly. Compared with normal group ， positive expression，mRNA and protein expression of TRPV 1，CGRP， CRLR and RAMP 1 in TCC of rats in the model group were significantly increased （P＜0.05）. Compared with model zengguirong@hnse.org group， most of above indicators in Xiongma decoction effective fraction groups were significantly decreased （P＜0.05）. CONCLUSIONS The mechanism of Xiongma decoction in preventing and treating migraine with hyperactivity of liver-yang and blood stasis may be related to inhibit the activity of TRPV1-CGRP/CGRP receptor signaling pathway in TCC.

Objective:To evaluate the immunogenicity and immune persistence of purified Vero cells rabies vaccine (PVRV) with Zagreb and Essen regimen.Methods:Prospective study: Patients with first Class II exposure to rabies were recruited from the Dog Injury Cinic of Guangxi Center for Disease Control and Prevention (Guangxi CDC) and randomly divided into the Zagreb (2-1-1) and Essen (1-1-1-1-1) regimen group. All patients were inoculated with the vaccines from the same manufacturer and batch, and 3 ml serum was collected at the 45th day and in 1-year, 2-year and 3-year after immunization. Rapid fluorescent inhibition test (RFFIT) was used to detect rabies virus neutralizing antibody (RVNA). The attenuation of RVNA positive rate and geometric mean titer (GMT) with time was analyzed. Retrospective study: The informed consents for rabies vaccine in the Dog Injury Clinic of Guangxi CDC were checked out. The patients who were injected with PVRV (same manufacturer but unlimited batch) but without passive immune agents for the first time within 3 years were selected and divided into 1-year, 2-year and 3-year group. Each group was further divided into Zagreb and Essen regimen group. The serum (3 ml) was collected at 1 year, 2 years and 3 years after immunization and detected the RVNA by RFFIT.Results:Prospective study: The RVNA positive rates on the 45th day and in 1-year, 2-year and 3-year after immunizationin in the Zagreb and Essen regimen group were 100%, 95%, 85%, 80% and 98.25%, 89.47%, 89.47%, 85.96%, respectively. There was no statistically significant difference in the RVNA positive rates at the same time point between the two regimen groups ( P>0.05). The RVNA GMT on the 45th day and in 1-year, 2-year, and 3-year in the Zagreb and Essen regimen group were 11.32 IU/ml, 1.69 IU/ml, 1.30 IU/ml, 1.30 IU/m and 13.18 IU/ml, 2.13 IU/ml, 1.87 IU/ml, 1.84 IU/m, respectively. There was no significant difference in the RVNA GMT levels at the same time point between the two regimen groups ( F=1.971, P=0.164). The RVNA GMT levels in the two regimen groups had the same trend of attenuation over time (time*group F=0.702, P=0.435). Retrospective study: The RVNA positive rates in 1-year, 2-year and 3-year after immunization in the Zagreb and Essen regimen group were 100%, 95%, 91.43%和94.73%, 86.21%, 87.5%, respectively. There was no statistically significant difference in the RVNA positive rates at the same time point between the two regimen groups ( P>0.05). The RVNA GMT in 1-year, 2-year, and 3-year groups after immunization in the Zagreb and Essen regimen group were 2.65 IU/ml, 2.03 IU/ml, 1.57 IU/ml和3.2 IU/ml, 2.58 IU/ml, 2.45 IU/ml, respectively. There was no significant difference in the RVNA GMT levels at the same time point between the two regimen groups ( P>0.05). Conclusions:The PVRV showed the same excellent immunogenicity and immune persistence after the vaccination with the Zagreb and Essen regimens.

ABSTRACT OBJECTIVE：To study the effects of the extract of Xiongmatang on 5-HT and CGRP in brain tissue of rats with liver-yang hyperactivity and blood stagnation migraine. METHODS：Fifty male spontaneously hypertension （SHR） rats were randomly divided into model control group，Zhengtian pill positive control group （1.6 g/kg），the extract of Xiongmatang low-dose，medium-dose and high-dose groups（4.5，9.0，18.0 g/kg，by crude drug），with 10 rats in each group. Another 10 normal rats were taken as normal control group. Administration group was given relevant medicine intragastrically，once a day，for consecutive 28 d. Normal control group and model control group were given equal volume normal saline intragastrically. After last administration，except for normal control group，other groups were used to stimulate trigeminal ganglia（10 min）to establish liver-yang hyperactivity and blood stagnation migraine model，and maintained the administration once more after making the model. 30 min later，general behavior and tongue quality of rats were observed，and the blood pressure was measured；the contents of 5-HT and CGRP in cerebral tissue of rats were determined by ELISA. The protein expression of CGRP in cerebral tissue of rats were determined by Western blot method. RESULTS： Compared with the normal control group， the rats in the model control group had behavioral symptoms，such as the color of conjunctiva deepened and reddened， excessive hairdressing，head flicking，and most of the rats had purple tongue；the systolic pressure and the content and protein expression of CGRP were all increased obviously（P＜0.05 or P＜0.01）， while the content of 5-HT in cerebral tissue was decreased obviously（P＜0.01）. Compared with model control group，general behavior and tongue quality of rats were improved significantly in administration groups. Systolic pressure，the content and the protein expression of CGRP in cerebral tissue of rats were decreased significantly in Zhengtian pill positive control group and the extract of Xiongmatang high-dose group （P＜0.05），while the content of 5-HT in cerebral tissue of rats were increased significantly in Zhengtian pill positive control group，the extract of Xiongmatang medium-dose and high-dose groups（P＜0.05）.CONCLUSIONS：The extract of Xiongmatang has obvious protective effect on liver-yang hyperactivity and blood stagnation migraine model rats，the mechanism of which may be associated with reducing the content of CGRP in cerebral tissue and raising the content of 5-HT in cerebral tissue

Objective To observe the improving effect of Hypericum Perforatum L Extracts (HPLES)on depression induced by chronic unpredictable mild stress in mice. Methods The depression model was established by the method of chronic unpredictable mild stress. Fifty depression model mice were divided into model control group,fluoxetine hydrochloride group (2. 6 mg / kg),Hypericum perforatum ex-tract low,medium and high (0. 2 g / kg,0. 4 g / kg,0. 8 g / kg) dose groups according to the random num-ber table method. Another 10 normal mice matched with body weight were taken as the normal control group. The mice in normal control group and the model control group were given pure water by gavage every day,and the mice in other groups were given corresponding solution by gavage for 4 weeks. In addition to the normal control group,the mice in other groups continued to undergo chronic unpredictable mild stress during gavage. The sugar water preference test and forced swimming test were performed after the last administration. Blood samples were collected from the posterior orbital venous plexus,and the levels of dopamine (DA) and brain-derived neurotrophic factor (BDNF) were measured by Elisa. The hippocampal tissues of mice were exam-ined by HE staining. Results Compared with the normal control group,the body mass of mice in the model control group decreased significantly at the first,second,third and fourth weeks ( t=2. 739,4. 162,4. 082, 3. 957;all P<0. 05). At the first,second,third and fourth weeks,the body mass of mice in the low,middle and high dose group of Hypericum perforatum extract were not significantly different from those in the model control group (all P>0. 05). Compared with the normal control group,the sugar water preference index of mice in the model control group was significantly reduced((61. 3± 4. 5)%,(52. 6± 5. 2)%; t=2. 721,P<0. 05),the swimming immobility time was prolonged(( 44. 3± 20. 00) s,(101. 8± 50. 8) s;t=2. 939,P<0. 05),the difference were statistically significant. Compared with the model control group,the sugar water preference index of mice in the low,middle and high dose group of Hypericum perforatum extract increased ((61. 8±4. 7)%,(65. 2±4. 1)%,(62. 6±5. 6)%,t=-3. 005,5. 073,-2. 928,all P<0. 05),the swimming immobility time decreased ((47. 2±17. 9) s,(54. 8±50. 3) s,(61. 3±44. 2) s; t=2. 803,1. 921,1. 903,all P<0. 05). The results of Elisa showed that compared with the normal control group,the levels of serum DA and BDNF of mice in the model control group were significantly lower (t=3. 031,8. 507,all P<0. 05); com-pared with the model control group,the levels of serum DA of mice in the low dose and high dose group of Hypericum perforatum were significantly higher (t=5. 025,3. 414,P<0. 05),and the serum BDNF of mice in the high dose group of Hypericum perforatum was also significantly higher (t=6. 098,P<0. 05),the differ-ence was statistically significant. HE staining showed that compared with the normal control group,the neu-rons in CA3 area of hippocampus in the model control group mice were seriously damaged,suggesting the es-tablishment of the mouse model. Compared with the model control group,the atrophy and degeneration of hippocampal CA3 cells in the three dose groups were significantly reduced. The atrophy and deformation of hippocampal CA3 neurons in the low,middle and high dose groups of Hypericum perforatum extract were re-lieved. Conclusion HPLES have obvious improving and antidepressant effects on the depression model mice induced by chronic unpredictable stress. The above effects may be related to the improvement of serum DA,DBNF level and reduce neuronal damage in CA3 area.

To study the protective effect of Xingnaojing Injection on early global brain ischemia-induced deep coma in rats.
 Methods: The deep coma model was induced by global brain ischemia by using four-vessel occlusion method in male SD rats. According to the body weight, the rats were randomly divided into 8 groups: a model control group, three different dose of Xingnaojing Injection (1.8, 3.6 and 5.4 mL.kg-1) groups, a Xingnaojing Injection (3.6 mL.kg-1) plus PI3K inhibitor group, a naloxone injection (0.04 mL.kg-1) group and a naloxone injection (0.04 mL.kg-1) plus Xingnaojing Injection (3.6 mL.kg-1) group (n=8 per group). In addition, eight animals served as the sham group were performed same operation with the model group excepting no blockage of the blood vessels. After the operation, three different doses of Xingnaojing Injection and/or naloxone injection were given intravenously once a day for three days. Ten μL PI3K inhibitor (LY294002, 10 mmol/L) was injected via anterior cerebral ventricle at once after global brain ischemia. The awakening time after the first drug treatment, the grasping power and the autonomous activity within 10 min after the last drug treatment were recorded. The levels of both dopamine (DA) and glutamate (Glu) in cerebrospinal fluid were detected by ELISA. The pathological changes were observed in brain tissue slices with HE staining and the protein levels of Akt/p-Akt and cAMP-response element binding protein (CREB)/p-CREB in hippocampus were detected by Western blotting.
 Results: Comparing with the model group, single administration of Xingnaojing Injection could significantly shorten the waking time (P<0.05) and continuous administration of Xingnaojing Injection for 3 d could increase grasping power, distance, frequency and duration of autonomous activities (P<0.05 or P<0.01) in the deep coma rat. Also, Xingnaojing Injection could inhibit these increases in neurotransmitters DA and Glu contents (P<0.05 or P<0.01), and improve pathological changes of hippocampal tissue. Xingnaojing Injection significantly induced protein phosphorylation of both Akt and CREB (P<0.05 or P<0.01); this effect was inhibited by PI3K inhibitor (P<0.05 or P<0.01). Moreover, the protective effects of naloxone on awakening time, grasping power, the autonomous activity and hippocampus damage in global brain ischemia-induced deep coma could be enhanced by joint use of Xingnaojing Injection (P<0.05 or P<0.01).
 Conclusion: Xingnaojing Injection could significantly improve deep coma induced by global brain ischemia in rat, which is related to inducing PI3K/Akt-dependent protein phosphorylation of CREB, and reducing hippocampal damage. The protective effect of Xingnaojing Injection is synergistically enhanced by naloxone.
Animals ; Brain ; Brain Ischemia ; Coma ; Drugs, Chinese Herbal ; Male ; Phosphatidylinositol 3-Kinases ; Rats ; Rats, Sprague-Dawley

Objective: To observe the improving effect of Hypericum Perforatum L Extracts (HPLES)on depression induced by chronic unpredictable mild stress in mice. Methods: The depression model was established by the method of chronic unpredictable mild stress. Fifty depression model mice were divided into model control group, fluoxetine hydrochloride group (2.6 mg / kg), Hypericum perforatum extract low, medium and high (0.2 g / kg, 0.4 g / kg, 0.8 g / kg) dose groups according to the random number table method. Another 10 normal mice matched with body weight were taken as the normal control group. The mice in normal control group and the model control group were given pure water by gavage every day, and the mice in other groups were given corresponding solution by gavage for 4 weeks. In addition to the normal control group, the mice in other groups continued to undergo chronic unpredictable mild stress during gavage.The sugar water preference test and forced swimming test were performed after the last administration. Blood samples were collected from the posterior orbital venous plexus, and the levels of dopamine (DA) and brain-derived neurotrophic factor (BDNF) were measured by Elisa. The hippocampal tissues of mice were examined by HE staining. Results: Compared with the normal control group, the body mass of mice in the model control group decreased significantly at the first, second, third and fourth weeks (t=2.739, 4.162, 4.082, 3.957; all P<0.05). At the first, second, third and fourth weeks, the body mass of mice in the low, middle and high dose group of Hypericum perforatum extract were not significantly different from those in the model control group (all P>0.05). Compared with the normal control group, the sugar water preference index of mice in the model control group was significantly reduced((61.3±4.5)%, (52.6±5.2)%; t=2.721, P<0.05), the swimming immobility time was prolonged((44.3±20.00) s, (101.8±50.8) s; t=2.939, P<0.05), the difference were statistically significant. Compared with the model control group, the sugar water preference index of mice in the low, middle and high dose group of Hypericum perforatum extract increased((61.8±4.7)%, (65.2±4.1)%, (62.6±5.6)%, t=-3.005, 5.073, -2.928, all P<0.05), the swimming immobility time decreased ((47.2±17.9) s, (54.8±50.3) s, (61.3±44.2) s; t=2.803, 1.921, 1.903, all P<0.05). The results of Elisa showed that compared with the normal control group, the levels of serum DA and BDNF of mice in the model control group were significantly lower (t=3.031, 8.507, all P<0.05); compared with the model control group, the levels of serum DA of mice in the low dose and high dose group of Hypericum perforatum were significantly higher (t=5.025, 3.414, P<0.05), and the serum BDNF of mice in the high dose group of Hypericum perforatum was also significantly higher (t=6.098, P<0.05), the difference was statistically significant. HE staining showed that compared with the normal control group, the neurons in CA3 area of hippocampus in the model control group mice were seriously damaged, suggesting the establishment of the mouse model. Compared with the model control group, the atrophy and degeneration of hippocampal CA3 cells in the three dose groups were significantly reduced. The atrophy and deformation of hippocampal CA3 neurons in the low, middle and high dose groups of Hypericum perforatum extract were relieved. Conclusion HPLES have obvious improving and antidepressant effects on the depression model mice induced by chronic unpredictable stress.The above effects may be related to the improvement of serum DA, DBNF level and reduce neuronal damage in CA3 area.

Adipocytokines are polypeptides or proteins that are secreted by fat cells with a wide range of biological activities. Adiponectin is a fatty cytokine with insulin sensitization. It possesses the function of anti- diabetes, atherosclerosis and anti-inflammation. Adiponectin may participate in regulating the development of cognitive impairment, which is considered as a new regulatory factor for cognitive impairment.
Adiponectin ; Cognitive Dysfunction ; Diabetes Mellitus ; Humans ; Insulin ; Insulin Resistance