ObjectiveTo explore the mechanism by which Banxia Xiexin Tang （BXT） regulates the advanced glycation end products （AGE）/receptor for advanced glycation end products （RAGE） signaling pathway to reduce neuroinflammatory responses and ameliorate cognitive dysfunction in the rat model of vascular dementia （VD）. MethodsThe components of BXT were detected by ultra performance liquid chromatography-quadrupole -orbitrap-tandem mass spectrometry（UPLC-Q-Orbitrap-MS/MS）， and the core components and key action pathways were screened out by network pharmacology and molecular docking. Sixty SPF-grade male SD rats were randomly allocated into the sham and modeling groups by the random number table method. The VD model was replicated by the modified bilateral occlusion of the common carotid arteries （2-VO） method. The successfully modeled rats were randomly allocated into the model， low-， medium-， and high-dose （3.748 5， 7.497， 14.994 g·kg^-1） BXT （BXT-L， BXT-M， and BXT-H）， and nimodipine （NMP， 0.002 7 g·kg^-1） groups according to the random number table method. The rats in the drug intervention groups were administrated with corresponding drugs by gavage， and the sham and model groups received the same amount of normal saline for 14 consecutive days. The Morris water maze， Y-maze， and new object recognition experiments were conducted to evaluate the cognitive dysfunction of rats. Hematoxylin-eosin （HE） staining was used to evaluate the histopathological changes of the hippocampal tissue in rats. The mRNA levels of AGE， RAGE， and phosphorylated nuclear factor-kappa B p65 （p-NF-κB p65） in the hippocampal tissue of rats were determined by Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）. The expression of related proteins in the AGE/RAGE pathway in the hippocampal tissue of rats was determined by Western blot and immunohistochemistry （IHC）. The levels of neurotransmitters and inflammatory mediators in the rat serum were measured by enzyme-linked immunosorbent assay （ELISA）. ResultsThe chemical components of BXT were detected by UPLC-Q-Orbitrap-MS/MS. Network pharmacology and molecular docking identified the AGE/RAGE pathway as the key pathway. The results of the water maze， Y maze， and novel object recognition tests showed that compared with the sham group， the model group demonstrated prolonged successful latency and decreases in number of platform crossings， alternation rate， number of entries into the new arm， preference index， and discrimination index （P0.01）. Compared with the model group， the BXT-H and BXT-M groups showed shortened successful latency （P0.01） and increases in number of platform crossings （P0.05）， alternation rate （P0.01）， number of entries into the new arm （P0.05）， preference index （P0.01）， and discrimination index （P0.01）. HE results showed that compared with the sham group， the cells of model rats were loosely and disorderly arranged， and the nuclei were condensed. Compared with the model group， the pathological changes of the hippocampus in the BXT group were mitigated. Real-time PCR results showed that compared with the sham group， the model group presented up-regulated mRNA levels of AGE， RAGE， and p-NF-κB p65 in the hippocampus （P0.01）， and compared with the model group， the BXT-H and BXT-M groups showcased down-regulated mRNA levels of AGE， RAGE， and p-NF-κB p65 （P0.01）. Western blot results showed that compared with the sham group， the model group presented up-regulated expression of AGE， RAGE， p-NF-κB p65， and tumor necrosis factor-α （TNF-α） （P0.05）， and compared with the model group， the BXT-H group presented down-regulated expression of AGE， RAGE， p-NF-κB p65， and TNF-α （P0.05）. IHC results showed that compared with the sham group， the model group had increased expression of RAGE （P0.01）， and compared with the model group， the BXT-H and BXT-M groups had reduced expression of RAGE （P0.01）. ELISA results showed that compared with the sham group， the model group exhibited elevated levels of TNF-α and Interleukin-1β （IL-1β） and declined levels of acetylcholine （ACh） and dopamine （DA） in the serum （P0.01）. Compared with the model group， the BXT-L， BXT-M， and BXT-H groups showed lowered levels of TNF-α and IL-1β in the serum （P0.05） and elevated levels of ACh and DA （P0.05）. ConclusionBXT may ameliorate cognitive dysfunction in the rat model of VD by down-regulating the AGE/RAGE signaling pathway， reducing neuroinflammatory responses， and regulating neurotransmitter levels.

Insomnia is a sleep disorder characterized by difficulty in falling asleep， sleep maintenance disorder and impaired daytime function. Its pathological mechanism involves multiple factors such as nerve excitability， circadian rhythm， cell apoptosis， oxidative stress injury. As a classical tyrosine kinase signaling pathway， phosphatidylinositol 3-kinase/protein kinase B（PI3K/Akt） triggers Akt phosphorylation cascade， inducing inflammatory response， apoptosis， autophagy， oxidative damage， nerve excitability， and circadian rhythm imbalance. Traditional Chinese medicine（TCM） can improve sleep by targeting the PI3K/Akt pathway. Based on this， this paper systematically reviews the research progress on the regulation of PI3K/Akt pathway by traditional Chinese medicine（TCM） for insomnia at home and abroad. These drugs can regulate neuronal excitability by regulating the PI3K/Akt pathway， affect the circadian rhythm， alleviate inflammation， apoptosis， autophagy and oxidative stress， and thus regulate sleep-wake. Furthermore， literature review indicates that the PI3K/Akt signaling pathway may represent a specific pathway underlying phlegm-turbidity disturbing the upper Jiao-type insomnia.

ObjectiveTo explore the mechanism by which Banxia Xiexin Tang （BXT） regulates the advanced glycation end products （AGE）/receptor for advanced glycation end products （RAGE） signaling pathway to reduce neuroinflammatory responses and ameliorate cognitive dysfunction in the rat model of vascular dementia （VD）. MethodsThe components of BXT were detected by ultra performance liquid chromatography-quadrupole -orbitrap-tandem mass spectrometry（UPLC-Q-Orbitrap-MS/MS）， and the core components and key action pathways were screened out by network pharmacology and molecular docking. Sixty SPF-grade male SD rats were randomly allocated into the sham and modeling groups by the random number table method. The VD model was replicated by the modified bilateral occlusion of the common carotid arteries （2-VO） method. The successfully modeled rats were randomly allocated into the model， low-， medium-， and high-dose （3.748 5， 7.497， 14.994 g·kg^-1） BXT （BXT-L， BXT-M， and BXT-H）， and nimodipine （NMP， 0.002 7 g·kg^-1） groups according to the random number table method. The rats in the drug intervention groups were administrated with corresponding drugs by gavage， and the sham and model groups received the same amount of normal saline for 14 consecutive days. The Morris water maze， Y-maze， and new object recognition experiments were conducted to evaluate the cognitive dysfunction of rats. Hematoxylin-eosin （HE） staining was used to evaluate the histopathological changes of the hippocampal tissue in rats. The mRNA levels of AGE， RAGE， and phosphorylated nuclear factor-kappa B p65 （p-NF-κB p65） in the hippocampal tissue of rats were determined by Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）. The expression of related proteins in the AGE/RAGE pathway in the hippocampal tissue of rats was determined by Western blot and immunohistochemistry （IHC）. The levels of neurotransmitters and inflammatory mediators in the rat serum were measured by enzyme-linked immunosorbent assay （ELISA）. ResultsThe chemical components of BXT were detected by UPLC-Q-Orbitrap-MS/MS. Network pharmacology and molecular docking identified the AGE/RAGE pathway as the key pathway. The results of the water maze， Y maze， and novel object recognition tests showed that compared with the sham group， the model group demonstrated prolonged successful latency and decreases in number of platform crossings， alternation rate， number of entries into the new arm， preference index， and discrimination index （P<0.01）. Compared with the model group， the BXT-H and BXT-M groups showed shortened successful latency （P<0.01） and increases in number of platform crossings （P<0.05）， alternation rate （P<0.01）， number of entries into the new arm （P<0.05）， preference index （P<0.01）， and discrimination index （P<0.01）. HE results showed that compared with the sham group， the cells of model rats were loosely and disorderly arranged， and the nuclei were condensed. Compared with the model group， the pathological changes of the hippocampus in the BXT group were mitigated. Real-time PCR results showed that compared with the sham group， the model group presented up-regulated mRNA levels of AGE， RAGE， and p-NF-κB p65 in the hippocampus （P<0.01）， and compared with the model group， the BXT-H and BXT-M groups showcased down-regulated mRNA levels of AGE， RAGE， and p-NF-κB p65 （P<0.01）. Western blot results showed that compared with the sham group， the model group presented up-regulated expression of AGE， RAGE， p-NF-κB p65， and tumor necrosis factor-α （TNF-α） （P<0.05）， and compared with the model group， the BXT-H group presented down-regulated expression of AGE， RAGE， p-NF-κB p65， and TNF-α （P<0.05）. IHC results showed that compared with the sham group， the model group had increased expression of RAGE （P<0.01）， and compared with the model group， the BXT-H and BXT-M groups had reduced expression of RAGE （P<0.01）. ELISA results showed that compared with the sham group， the model group exhibited elevated levels of TNF-α and Interleukin-1β （IL-1β） and declined levels of acetylcholine （ACh） and dopamine （DA） in the serum （P<0.01）. Compared with the model group， the BXT-L， BXT-M， and BXT-H groups showed lowered levels of TNF-α and IL-1β in the serum （P<0.05） and elevated levels of ACh and DA （P<0.05）. ConclusionBXT may ameliorate cognitive dysfunction in the rat model of VD by down-regulating the AGE/RAGE signaling pathway， reducing neuroinflammatory responses， and regulating neurotransmitter levels.

Insomnia is a sleep disorder characterized by difficulty in falling asleep， sleep maintenance disorder and impaired daytime function. Its pathological mechanism involves multiple factors such as nerve excitability， circadian rhythm， cell apoptosis， oxidative stress injury. As a classical tyrosine kinase signaling pathway， phosphatidylinositol 3-kinase/protein kinase B（PI3K/Akt） triggers Akt phosphorylation cascade， inducing inflammatory response， apoptosis， autophagy， oxidative damage， nerve excitability， and circadian rhythm imbalance. Traditional Chinese medicine（TCM） can improve sleep by targeting the PI3K/Akt pathway. Based on this， this paper systematically reviews the research progress on the regulation of PI3K/Akt pathway by traditional Chinese medicine（TCM） for insomnia at home and abroad. These drugs can regulate neuronal excitability by regulating the PI3K/Akt pathway， affect the circadian rhythm， alleviate inflammation， apoptosis， autophagy and oxidative stress， and thus regulate sleep-wake. Furthermore， literature review indicates that the PI3K/Akt signaling pathway may represent a specific pathway underlying phlegm-turbidity disturbing the upper Jiao-type insomnia.

Objective This study aimed to investigate the effect of acupoint injection on glycometabolism in patients with Polycystic ovary syndrome(PCOS).Methods Eighty patients who were newly diagnosed with polycystic ovary syndrome(PCOS)in our hospital were randomly allocated into two groups:a control group and a treatment group,with 40 cases in each group.The two groups were treated with dietary exercise lifestyle and dietary exercise lifestyle+acupoint injection intervention for 3 months,respectively.The basal disposition index(DI0),early-phase disposition index(DI30),and total disposition index(DI120)represented β-cell function at fasting,early phase,and 120 minutes during the oral glucose tolerance test(OGTT).The homeostatic model assessment for insulin resistance(HOMA-IR)and the M value obtained from the high insulin-euglycemic clamp(HEC)test indicated insulin sensitivity.The changes in anthropometric indicators[waist-to-hip ratio(WHR),body mass index(BMI)],blood glucose and insulin levels[fasting blood glucose(Glu0),2 h post-OGTT blood glucose(Glu120),fasting insulin(Ins0),2 h post-OGTT insulin(Ins120),and glycated hemoglobin A1c(HbA1c)],sex hormones[free testosterone index(FAI),luteinizing hormone/follicle-stimulating hormone(LH/FSH)],pancreatic β-cell function and insulin sensitivity,oxidative stress[malondialdehyde(MDA),Cu/Zn superoxide dismutase(Cu/Zn SOD),glutathione peroxidase 1(GPX1)],and inflammation[interleukin-6(IL-6),interleukin-1β(IL-1β),tumor necrosis factor-α(TNF-α)]were compared before and after treatment,and safety observations were conducted.Results The baseline levels of the two groups were consistent(P>0.05);after treatment,the Glu0,Ins0,HOMA-IR,MDA,IL-6,IL-1β,and TNF-α in the treatment group were significantly reduced compared to those observed in the control group(P<0.05,P<0.01),while DI0,DI120,M value,Cu/Zn SOD,and GPX1 were higher than those in the control group(P<0.05,P<0.01).However,there were no statistically significant differences in anthropometric indicators,sex hormones,and other glucose metabolism indicators(P>0.05),and the incidence of adverse reactions between the two groups was not statistically significant(P>0.05).Conclusion Acupoint injection can alleviate glycometabolism in patients with PCOS of kidney deficiency and blood stasis to a certain extent,improve systemic oxidative stress and inflammatory status,and provide a possible external treatment method in traditional Chinese medicine for these patients.

Objective This study aimed to investigate the effect of acupoint injection on glycometabolism in patients with Polycystic ovary syndrome(PCOS).Methods Eighty patients who were newly diagnosed with polycystic ovary syndrome(PCOS)in our hospital were randomly allocated into two groups:a control group and a treatment group,with 40 cases in each group.The two groups were treated with dietary exercise lifestyle and dietary exercise lifestyle+acupoint injection intervention for 3 months,respectively.The basal disposition index(DI0),early-phase disposition index(DI30),and total disposition index(DI120)represented β-cell function at fasting,early phase,and 120 minutes during the oral glucose tolerance test(OGTT).The homeostatic model assessment for insulin resistance(HOMA-IR)and the M value obtained from the high insulin-euglycemic clamp(HEC)test indicated insulin sensitivity.The changes in anthropometric indicators[waist-to-hip ratio(WHR),body mass index(BMI)],blood glucose and insulin levels[fasting blood glucose(Glu0),2 h post-OGTT blood glucose(Glu120),fasting insulin(Ins0),2 h post-OGTT insulin(Ins120),and glycated hemoglobin A1c(HbA1c)],sex hormones[free testosterone index(FAI),luteinizing hormone/follicle-stimulating hormone(LH/FSH)],pancreatic β-cell function and insulin sensitivity,oxidative stress[malondialdehyde(MDA),Cu/Zn superoxide dismutase(Cu/Zn SOD),glutathione peroxidase 1(GPX1)],and inflammation[interleukin-6(IL-6),interleukin-1β(IL-1β),tumor necrosis factor-α(TNF-α)]were compared before and after treatment,and safety observations were conducted.Results The baseline levels of the two groups were consistent(P>0.05);after treatment,the Glu0,Ins0,HOMA-IR,MDA,IL-6,IL-1β,and TNF-α in the treatment group were significantly reduced compared to those observed in the control group(P<0.05,P<0.01),while DI0,DI120,M value,Cu/Zn SOD,and GPX1 were higher than those in the control group(P<0.05,P<0.01).However,there were no statistically significant differences in anthropometric indicators,sex hormones,and other glucose metabolism indicators(P>0.05),and the incidence of adverse reactions between the two groups was not statistically significant(P>0.05).Conclusion Acupoint injection can alleviate glycometabolism in patients with PCOS of kidney deficiency and blood stasis to a certain extent,improve systemic oxidative stress and inflammatory status,and provide a possible external treatment method in traditional Chinese medicine for these patients.

Objective:To observe the effects of Banxia Shumi Decoction on 5-HT 1AR, 5-HT 2AR, 5-HT, and 5-HIAA of chronic insomnia (CI) rats with internal obstruction of phlegm-damp (IOPD) type, to investigate the mechanisms of Banxia Shumi Decoction on resolving and draining dampness, guiding yang into yin and tranquilizing mind. Methods:A total of 48 Wistar rats were divided into control group, model group, Banxia Shumi Decoction low-dosage group, medium-dosage group, high-dosage group, and diazepam group according to random number table method, with 8 rats in each group. Except the control group, the CI with IOPD rats model were prepared by the method of "high-fat diet + single-platform water environment" in other groups. The rats in the Banxia Shumi Decoction low-, medium-, high-dosage group were treated with Banxia Shumi Decoction by gavage at the dose of 4.69, 9.38 and 18.75 g/kg respectively, the rats in the diazepam group were given 0.52 mg/kg diazepam aqueous solution by gavage, and the rats in the control group and model group were given the equal volume normal saline, once a day for consecutive 2 weeks. The mRNA expressions of 5-HT 1AR, 5-HT 2AR in rat brain stem were detected by qPCR, the protein expressions of 5-HT 1AR, 5-HT 2AR in rat brain raphe nucleus were detected by Western blot, and the contents of 5-HT and 5-HIAA in rat brain stem were determined by HPLC-MS. Results:Compared with model group, the expression of 5-HT 1AR mRNA significantly increased in the Banxia Shumi Decoction low-, medium-, high-dosage group, and diazepam group ( P<0.01); the expression of 5-HT 2AR mRNA significantly decreased in the Banxia Shumi Decoction high-dosage group and diazepam group ( P<0.05), and the expression of 5-HT 1AR and 5-HT 2AR significantly increased in the Banxia Shumi Decoction high-dosage group and diazepam group ( P<0.05 or P<0.01); 5-HT content significantly increased in the Banxia Shumi Decoction medium-, high-dosage group and diazepam group ( P<0.05 or P<0.01); 5-HIAA content significantly increased in the Banxia Shumi Decoction low-, medium-, high-dosage group, and diazepam group ( P<0.05 or P<0.01). Conclusion:Banxia Shumi Decoction may intervene CI with IOPD type and perform the actions of resolving and draining dampness, guiding yang into yin and tranquilizing mind by regulating the expressions of 5-HT 1AR, 5-HT 2AR, 5-HT and 5-HIAA.

Objective:To determine neutralizing antibodies against Japanese encephalitis virus (JEV) among healthy people of Southeast Gansu province, and to evaluate immunologic barrier, and provide the data for Japanese encephalitis (JE) control.Methods:Healthy people were divided into the following 3 groups: less than 14 years, 15-39 years, and above 40 years in 2018 in four cities (Pingliang city, Qingyang city, Longnan city, Tianshui city) of Southeast Gansu province. Serum samples of the participants were obtained, and JEV antibody was detected by plaque reduction neutralization assays. The JEV neutralizing antibody positive rates among different groups were compared by chi square test.Results:A total of 1 590 people were investigated. The total positive rate of JEV neutralizing antibody was 28.81%, and the geometric mean titer (GMT) of JEV neutralizing antibody was 1∶27.09. The antibody positive rates of 0-14, 15-39 and ≥ 40 years groups were 32.96%, 20.32%, 30.63%, the difference of antibody positive rates among different age groups was statistically significant ( χ2=22.29, P<0.001). The antibody positive rates in Pingliang city, Qingyang city, Longnan city, Tianshui city were 29.62%, 22.22%, 33.00%, 30.30%, the difference of antibody positive rates among cities was statistically significant( χ2=12.39, P=0.006). Conclusions:The positive rates of neutralizing antibodies against JEV was low among healthy people in Southeast Gansu province, and there is an epidemic risk of JE.

Objective: To learn the status and influencing factors of the purchase of supplementary insurance for adverse events following immunization ( AEFI ) by parents in Changsha, so as to provide basis for the development of compensatory strategies. Methods: Stratified random sampling method was used to select the parents who lived in Changsha for more than six months and had children under seven years old as subjects. A questionnaire survey was conducted to collect the information about demographic features, awareness of AEFI and the purchase of supplementary insurance. Logistic regression model was used to analyze the influencing factors for purchasing supplementary insurance. Results: Among 712 respondents ( response rate, 94.93% ) , 354 ( 49.72% ) purchased supplementary insurance. The results of multivariate logistic regression analysis showed that the parents aged 36-71 years ( OR=0.325, 95%CI: 0.144-0.732 ) were less likely to purchase supplementary insurance; the parents who were aware of supplementary insurance ( OR=3.622, 95%CI: 2.218-5.913 ) and compensation range ( OR=1.332, 95%CI: 1.164-1.524 ) , and who scored higher in the knowledge and attitude of AEFI ( OR=1.137, 95%CI: 1.049-1.231 ) were more likely to purchase supplementary insurance. Conclusion About 49.72% of the parents purchased of supplementary insurance. Age, awareness of supplementary insurance and compensation range,as well as knowledge and attitude of AEFI were associated with the purchase of supplementary insurance.

OBJECTIVE:To study the effects of Ⅰ,Ⅱ crystal and amorphous forms of lercanidipine hydrochloride on the preparation,and provide theoretical basis for its development and consistency evaluation. METHODS:X-ray powder diffraction (XRD),infrared spectrophotometry(IR)and differential scanning calorimetry(DSC)were adopted to identify the 3 crystal forms of lercanidipine hydrochloride. XRD was used to compare the effects of crushing,grinding,pressing technology,wetting granula-tion,adhesive solvents(water,ethanol)and drying temperature(50,60,70℃)on stability of 3 crystal forms of lercanidipine hy-drochloride;the dissolution in vitro in water,hydrochloride,pH 4.5 acetate buffer,pH 6.8 phosphate buffer were compared among 3 crystal forms of Lercanidipine hydrochloride tablet. RESULTS:XRD showed both Ⅰ,Ⅱ crystal forms had characteristic diffrac-tion peak with inconsistent 2 θ values,amorphous had no characteristic diffraction peak;IR showed 3 crystal forms had different absorption intensity and absorption peak number;DSC showed Ⅰ,Ⅱ crystal forms had obvious endothermic peak in 194.6 ℃, 207.3 ℃,respectively,amorphous had obvious endothermic peak in 86.1 ℃ and exothermic peak in 299.8 ℃. Crushing,grinding, pressing and drying temperature had no effects on the stability of 3 crystal forms;water had no effect on the stability of crystal in wetting granulation,ethanol may cause the change of Ⅰcrystal form. Except for the comparison between Ⅰ,Ⅱ crystal forms in hydrochloride (f2=68),the dissolution f2 of 3 crystal forms in 4 kinds of medium were lower than 50. CONCLUSIONS:XRD, IR,DSC methods can identify the 3 crystal forms of Lercanidipine hydrochloride tablet. When preparing lercanidipine hydrochlo-ride by Ⅰcrystal form,wetting granulation should avoid using ethanol as a adhesive solvent,instead of water. Different crystal forms can affect the dissolution in vitro of prepared Lercanidipine hydrochloride tablet.