ObjectiveTo explore the pharmacological mechanism involved in the treatment of allergic cough （AC） by Xiaoer Huatan Zhike granules （XEHT） based on proteomics and network pharmacology. MethodsAfter sensitization by intraperitoneal injection of 1 mL suspension containing 2 mg ovalbumin （OVA） and 100 mg aluminum hydroxide， a guinea pig model of allergic cough was constructed by nebulization with 1% OVA. The modeled guinea pigs were randomized into the model， low-， medium- and high-dose （1， 5， 20 g·kg^-1， respectively） XEHT， and sodium montelukast （1 mg·kg^-1） groups （n=6）， and another 6 guinea pigs were selected as the blank group. The guinea pigs in drug administration groups were administrated with the corresponding drugs by gavage， and those in the blank and model groups received the same volume of normal saline by gavage， 1 time·d^-1. After 10 consecutive days of drug administration， the guinea pigs were stimulated by 1% OVA nebulization， and the coughs were observed. The pathological changes in the lung tissue were observed by hematoxylin-eosin staining. The enzyme-linked immunosorbent assay was performed to measure the levels of C-reactive protein （CRP）， interleukin-6 （IL-6）， tumor necrosis factor-α （TNF-α）， superoxide dismutase （SOD）， and malondialdehyde （MDA） in the bronchoalveolar lavage fluid （BALF） and immunoglobulin G （IgG） and immunoglobulin A （IgA） in the serum. Immunohistochemistry （IHC） was employed to observe the expression of IL-6 and TNF-α in the lung tissue. Transmission electron microscopy was employed observe the alveolar type Ⅱ epithelial cell ultrastructure. Real-time PCR was employed to determine the mRNA levels of IL-6， interleukin-1β （IL-1β）， and TNF-α in the lung tissue. Label-free proteomics was used to detect the differential proteins among groups. Network pharmacology was used to predict the targets of XEHT in treating AC. The Kyoto Encyclopedia of Genes and Genomes （KEGG） enrichment analysis was performed to search for the same pathways from the results of proteomics and network pharmacology. ResultsCompared with the blank group， the model group showed increased coughs （P<0.01）， elevated levels of CRP， TNF-α， IL-6， and MDA and lowered level of SOD in the BALF （P<0.05， P<0.01）， elevated levels of IgA and IgG in the serum （P<0.05， P<0.01）， congestion of the lung tissue and infiltration of inflammatory cells， increased expression of IL-6 and TNF-α （P<0.01）， large areas of low electron density edema in type Ⅱ epithelial cells， obvious swelling and vacuolization of the organelles， karyopyknosis or sparse and dissolved chromatin， and up-regulated mRNA levels of IL-6， IL-1β， and TNF-α （P<0.01）. Compared with the model group， the drug administration groups showed reduced coughs （P<0.01）， lowered levels of CRP， TNF-α， IL-6， and MDA and elevated level of SOD in the BALF （P<0.05， P<0.01）， alleviated lung tissue congestion， inflammatory cell infiltration， and type Ⅱ epithelial cell injury， and decreased expression of IL-6 and TNF-α （P<0.01）. In addition， the medium-dose XEHT group and the montelukast sodium group showcased lowered serum levels of IgA and IgG （P<0.05， P<0.01）. The medium- and high-dose XEHT groups and the montelukast sodium showed down-regulated mRNA levels of IL-6， IL-1β， and TNF-α and the low-dose XEHT group showed down-regulated mRNA levels of IL-6 and TNF-α （P<0.05， P<0.01）. Phospholipase D， mammalian target of rapamycin （mTOR）， and epidermal growth factor receptor family of receptor tyrosine kinase （ErbB） signaling pathways were the common pathways predicted by both proteomics and network pharmacology. ConclusionProteomics combined with network pharmacology reveal that XEHT can ameliorate AC by regulating the phospholipase D， mTOR， and ErbB signaling pathways.

Objective:To investigate the role of reactive astrocytes expressing aromatase(ARO)in the penumbra during ischemic stroke.Methods:A mouse model of middle cerebral artery occlusion(MCAO/R)was prepared using the suture method.Western blot and immunofluorescence staining were used to observe the expression of ARO in the penumbra after ischemia reperfusion.We generated a glial fibrillary acidic protein promoter-driven aromatase knock-out(GFAP-ARO-KO)mouse model in vivo.Neurologic impairment scores,rotarod test,grip strength test and adhesive removal test on the plantar surface of the paw were performed after MCAO/R modeling.Results:In wild type mice,the expression of ARO was significantly increased in astrocytes in the penumbra after MCAO/R(P<0.01).Compared to the control group,the expression of ARO in the GFAP-ARO-KO group was significantly reduced in astrocytes in the penumbra after MCAO/R.And loss of ARO increased cerebral infarction volume and aggravated sensorimotor impair-ment.Conclusion:After ischemic stroke,reactive astrocytes in the penumbra highly express ARO and play a protective role in post-ischemia reperfusion injury.

Objective:To investigate the role of reactive astrocytes expressing aromatase(ARO)in the penumbra during ischemic stroke.Methods:A mouse model of middle cerebral artery occlusion(MCAO/R)was prepared using the suture method.Western blot and immunofluorescence staining were used to observe the expression of ARO in the penumbra after ischemia reperfusion.We generated a glial fibrillary acidic protein promoter-driven aromatase knock-out(GFAP-ARO-KO)mouse model in vivo.Neurologic impairment scores,rotarod test,grip strength test and adhesive removal test on the plantar surface of the paw were performed after MCAO/R modeling.Results:In wild type mice,the expression of ARO was significantly increased in astrocytes in the penumbra after MCAO/R(P<0.01).Compared to the control group,the expression of ARO in the GFAP-ARO-KO group was significantly reduced in astrocytes in the penumbra after MCAO/R.And loss of ARO increased cerebral infarction volume and aggravated sensorimotor impair-ment.Conclusion:After ischemic stroke,reactive astrocytes in the penumbra highly express ARO and play a protective role in post-ischemia reperfusion injury.

OBJECTIVE To study the interventional effect and mechanism of 1，8-cineole on pancreatic β cell ferroptosis induced by type 2 diabetes. METHODS In vitro ferroptosis model was established in pancreatic β cells of mice by using high glucose. The effects of low-dose and high-dose 1，8-cineole （0.25， 0.5 μmol/L） on the level of Fe2+ in pancreatic β cells were investigated. The effects of 1，8-cineole （0.5 μmol/L） combined with ferroptosis inducer Erastin （20 μmol/L） and ferroptosis inhibitor Ferrostatin-1 （20 μmol/L） on the protein expressions of glutathione peroxidase-4 （GPX4） and cyclooxygenase-2 （COX2） were also detected. The type 2 diabetes model mice were established by feeding high-sugar and high-fat diet combined with intraperitoneal injection of streptozotocin. The effects of low-dose and high-dose 1，8-cineole （50， 200 mg/kg） on the pathological morphology of pancreatic tissue， the content of iron as well as the protein expressions of GPX4 and COX2 were investigated. RESULTS The results of the cell experiment showed that compared with the model group， pretreatment with 1，8-cineole significantly reduced intracellular Fe2+ levels and upregulated GPX4 protein expression， while downregulated COX2 protein expression in pancreatic β cells （P＜0.05）. After combining with Ferrostatin-1， the expression trends of the above two proteins were the same， while there was no statistically significant difference after combining with Erastin. The results of animal experiments showed that compared with the model group， after intervention with 1，8-cineole， the structure of the pancreatic islets in mice recovered intact and their morphology improved； the iron content of pancreatic tissue and protein expression of COX2 were decreased significantly （P＜0.05）， while protein expression of GPX4 was increased significantly （P＜0.05）. CONCLUSIONS 1，8-cineole could ameliorate pancreatic β cell injury induced by diabetes， the mechanism of which may be related to reducing intracellular iron deposition and regulating ferroptosis-related proteins.

OBJECTIVE：To provid e reference for the medicinal resources and clinical application of Tibetan medicine “Dida”. METHODS：Delphi method was adopted. By reviewing literatures ，confirming consultation scope ，inviting experts engaged in clinical，scientific research ，teaching and production of Tibetan medicine. Two methods ，online inquiry and on-site questionnaire ， were used for expert consultation to evaluate the differences and problems existing in the utilization of “Dida”medicinal resources until a consensus was reached ，consensus on the medicinal resources and clinical application of Tibetan medicine “Dida”was determined finally. RESULTS & CONCLUSIONS ：A total of 33 experts participated in the two rounds of consultation. According to the results of literature research ，the first round set up 16 inquiry indicators ；and then according to expert opinions to modify the index system ，the second round set up 18 inquiry indicators. After two rounds of inquiry ，a consensus was finally reached on 16 items on the original name ，quality standards and clinical application of Tibetan medicine “Dida”，and 2 items related to the characteristics and compatibilities of “Dida”had not reach common views. The consensuses of 16 items mainly cover the original name of “Dida”and the evolution of geographic information ，the rational selection of “Dida”medicinal materials ，the effectiveness and safety of clinical use of “Dida”.

Objective: To prospectively investigate the feasibility of shear wave elastography (SWE) as a new quantitative and objective method for evaluating the stiffness of the gastrocnemius medialis (GM) muscle during passive stretching in patients with Parkinson’s disease (PD). Materials and Methods: SWE of the GM muscle was performed in 28 patients with PD [13 female and 15 male; mean age ± standard deviation (SD): 63.0 ± 8.5 years] and 12 healthy controls (5 female and 7 male; mean age ± SD: 59.3 ± 6.4 years) during passive ankle rotation. A Young’s modulus-ankle angle curve was constructed. The GM slack angle and baseline Young’s modulus (E 0) were compared between the markedly symptomatic and mildly symptomatic sides of patients with PD, and healthy controls. Additionally, the correlation between the GM slack angle and the severity of rigidity, and the observer reproducibility of SWE in determining the GM slack angle were evaluated. Results: The GM slack angle was smaller on both the markedly and mildly symptomatic sides in patients with PD than in healthy controls (mean ± SD of -29.13° ± 3.79° and -25.65° ± 3.39°, respectively, vs. -21.22° ± 3.52°; p < 0.001 and p = 0.006, respectively). Additionally, in patients with PD, the GM slack angle on the markedly symptomatic side was smaller than that on the mildly symptomatic side (p = 0.003). The E 0 value was lower on both the markedly and mildly symptomatic sides in patients with PD than in healthy controls (mean ± SD of 10.11 ± 2.85 kPa and 10.08 ± 1.88 kPa, respectively, vs. 12.23 ± 1.02 kPa; p = 0.012 and p < 0.001, respectively). However, no significant difference was found between the markedly and mildly symptomatic sides in patients with PD (p = 0.634). A negative linear relationship was observed between the GM slack angle and lower limb rigidity score on the markedly symptomatic side in patients with PD (r = -0.719; p < 0.001). The intraclass correlation coefficients for observer reproducibility of SWE ranged from 0.880 to 0.951. Conclusion The slack angle determined by SWE may be a useful quantitative and reproducible method for evaluating muscle stiffness in patients with PD.

Objective:This study aims to investigate the prevalence and distribution characteristics of mental disorders among people aged 18 and above in Shandong Province.Methods:In 2015, an epidemiological survey was carried out to investigate the patterns of mental disorders in 49 counties of Shandong Province. A total of 28 000 individuals aged 18 years or older were selected using the multistage stratified cluster sampling method. All these participants were classified as at a high or low risk of mental disorders according to the assessment results of the revised version of the General Health Questionnaire (GHQ). The diagnosis of mental disorders was confirmed using the Structured Clinical Interview for Diagnostic and Statistical Manual, Forth edition (DSM-Ⅳ) axis I or MMSE. All participants at high risk of mental disorders were evaluated using DSM-Ⅳ or MMSE to confirm the psychiatric diagnoses, while 10% of participants at low risk of mental disorders were randomly selected to be evaluated. The prevalence and its 95% confidence interval of mental disorders were adjusted according to study design and sociodemographic characteristics of the sample. The between-group differences of prevalence were compared using chi-square tests or Fisher′s exact tests as appropriately.Results:A total of 27 489 individuals completed survey. The adjusted prevalence of any mental disorder was 17.46% (95 %CI 17.02%-17.89%). The five most prevalent mental disorder spectrums were substance use disorders (5.29%), mood disorders (4.47%), anxiety disorders (4.46%), intellectual and mental disorders due to physical or substance (1.91%), and psychotic disorders (1.12%). The most common mental disorders were alcohol use disorder (5.27%) and major depressive disorder (2.14%). The prevalence of mental disorders in men was higher than that in women (23.37% vs. 13.89%; χ 2=408.91, P<0.01). There was no significant difference in the prevalence of mental disorders between rural residents and urban residents (17.69% vs. 17.20%; χ2=1.05, P=0.305). Of participants with mental disorders, 26.12% (1 047/4 008) had moderate to severe functional impairment and 10.98% (428/3 898) have sought professional help. Conclusion:The prevalence of mental disorders among people aged 18 and above in Shandong Province is basically consistent with the results of similar domestic studies. The prevalence of mental disorder was higher in men than in women and was not differ in participants living in urban and rural areas. Alcohol use disorder, major depressive disorder, non-specific anxiety disorder and non-specific depressive disorder are most common mental disorders.

Objective:This study aims to investigate the prevalence and distribution characteristics of mental disorders among people aged 18 and above in Shandong Province.Methods:In 2015, an epidemiological survey was carried out to investigate the patterns of mental disorders in 49 counties of Shandong Province. A total of 28 000 individuals aged 18 years or older were selected using the multistage stratified cluster sampling method. All these participants were classified as at a high or low risk of mental disorders according to the assessment results of the revised version of the General Health Questionnaire (GHQ). The diagnosis of mental disorders was confirmed using the Structured Clinical Interview for Diagnostic and Statistical Manual, Forth edition (DSM-Ⅳ) axis I or MMSE. All participants at high risk of mental disorders were evaluated using DSM-Ⅳ or MMSE to confirm the psychiatric diagnoses, while 10% of participants at low risk of mental disorders were randomly selected to be evaluated. The prevalence and its 95% confidence interval of mental disorders were adjusted according to study design and sociodemographic characteristics of the sample. The between-group differences of prevalence were compared using chi-square tests or Fisher′s exact tests as appropriately.Results:A total of 27 489 individuals completed survey. The adjusted prevalence of any mental disorder was 17.46% (95 %CI 17.02%-17.89%). The five most prevalent mental disorder spectrums were substance use disorders (5.29%), mood disorders (4.47%), anxiety disorders (4.46%), intellectual and mental disorders due to physical or substance (1.91%), and psychotic disorders (1.12%). The most common mental disorders were alcohol use disorder (5.27%) and major depressive disorder (2.14%). The prevalence of mental disorders in men was higher than that in women (23.37% vs. 13.89%; χ 2=408.91, P<0.01). There was no significant difference in the prevalence of mental disorders between rural residents and urban residents (17.69% vs. 17.20%; χ2=1.05, P=0.305). Of participants with mental disorders, 26.12% (1 047/4 008) had moderate to severe functional impairment and 10.98% (428/3 898) have sought professional help. Conclusion:The prevalence of mental disorders among people aged 18 and above in Shandong Province is basically consistent with the results of similar domestic studies. The prevalence of mental disorder was higher in men than in women and was not differ in participants living in urban and rural areas. Alcohol use disorder, major depressive disorder, non-specific anxiety disorder and non-specific depressive disorder are most common mental disorders.

Objective:To explore the changes of estrogen, androgen and progesterone in serum of male patients with primary gouty arthritis (pGA) and their possible role in the pathogenesis of gout.Methods:The serum, clinical data and laboratory parameters of 266 patients with PGA [including 93 patients with acute gout (AG), 118 patients with intermittent gout (IG), 55 patients with chronic gout (CG)] and 129 healthy controls (HC) were collected. The serum estradiol (E 2), progesterone (P), testosterone (T) and E 2/T were detected by CMIA Expression level. SPSS 17.0 statistical software was used for analysis, Wilcoxon rank sum test was used for comparison of measurement data between groups, and Spearman correlation analysis was used for correlation analysis between variables. Results:① The level of E 2 and T level in the serum of PGA, AG, IG and CG group was lower than that of the HC group [(30±8) pg/ml, (27±7) pg/ml, (31±8) pg/ml, (34±7) pg/ml, (35±10) pg/ml; F=17.770, P<0.05] and [(4.4±1.6) ng/ml, (3.8±1.4) ng/ml, (4.6±1.4) ng/ml, (5.1±2.0) ng/ml, (5.8±1.9) ng/ml; F=23.314, P<0.05], but there was no significant difference between HC group and CG group ( P>0.05), The serum E 2 and T levels in AG group were lower than those in IG and CG groups [(27±7) pg/ml, (31±8) pg/ml, (34±7) pg/ml; F=17.770, P<0.05] and [(3.8±1.4) ng/ml, (4.6±1.4) ng/ml, (5.1±2.0) ng/ml; F=23.314, P<0.05], andthe serum E 2 level in IG group was lower than that in CG group [(31±8) pg/ml, (34±7) pg/ml; F=17.770, P<0.05). The levels of P and E 2/T in HC group were lower than those in pGA and AG group [(0.24±0.10) ng/ml, (0.27±0.11)ng/ml, (0.30±0.15) ng/ml; F=5.124, P<0.05] and [(0.006 6±0.002 2) ng/ml, (0.007 6±0.003 2) ng/ml, (0.008 0±0.003 8) ng/ml; F=3.787, P<0.05), while those in IG and CG group were lower than those in AG group [(0.25±0.09) ng/ml, (0.26±0.08) ng/ml, (0.30±0.15) ng/ml; F=5.124, P<0.05]; ② Spearman correlation analysis showed that E 2 level in pGA group was positively correlated with T and CysC( r=0.310, P<0.01; r=0.164, P=0.008), negatively correlated with MO ( r=-0.133, P=0.030), P level was positively correlated with MO ( r=0.139, P=0.023), T level was positively correlated with Crea and CysC ( r=0.179, P=0.003; r=0.162, P=0.008), negatively correlated with WBC, GR and MO ( r=-0.140, P=0.022; r=-0.173, P=0.005; r=-0.149, P=0.015), E 2/T was positively correlated with apob1 and Glu ( r=0.131, P=0.032; r=0.140, P=0.023). In AG group, E 2 level was positively correlated with T and Crea ( r=0.234, P=0.024; r=0.245, P=0.018), T level was positively correlated with Crea ( r=0.349, P=0.001), and negatively correlated with apob1 ( r=-0.250, P=0.016), and E 2/T was positively correlated with apob1 ( r=0.276, P=0.007). In IG group, E 2 level was positively correlated with T ( r=0.269, P=0.003), and negatively correlated with MO ( r=-0.183, P=0.048), while P level was positively correlated with MO( r=0.204, P=0.027). Conclusion:The expression of E 2 and T in the peripheral blood serum of gout patients decreases significantly, the expression of P and E 2/T increases significantly, and there is a positive correlation between E 2 and T, as well as the inflammatory and glycolipid metabolism indexes of gout patients, suggesting that estrogen, androgen and progesterone may participate in the pathogenesis of gout by regulating the inflammation and metabolism of gout.

Objective:To explore efficacy and safety of endovascular therapy combined with hyperbaric oxygen (HBO) intervention in acute anterior circulation macrovascular occlusion stroke.Methods:A total of 150 patients with acute anterior circulation macrovascular occlusive stroke admitted in No.902 Hospital of the CPLA Joint Logistic Support Force were selected and randomly divided into endovascular treatment group and combined treatment group (endovascular+ HBO). Endovascular therapy was adopted in the treatment of all patients. Modified thrombolytic flow grading (mTICI) was used to evaluate vascular recanalization after operation, and the incidences of complications of hemorrhage transformation and vascular re-occlusion were recorded. National institutes of health stroke scale (NIHSS) was used to evaluate the neurological functions on admission, at 24 hours after the operation, and one course after HBO therapy. The prognosis was evaluated by observing the changes of blood homocysteine (HCY) and high-sensitivity C-reactive protein (hs-CRP) levels before and after treatment. The patients had been followed up by the modified Rankin Scale (mRS) for 90 days. At the same time, 75 patients with acute anterior circulation macrovascular occlusive stroke without taking endovascular treatment were selected as the control group.Results:Among 150 patients, 126 cases had a grade of mTICI≥2b, while 24 cases had a grade of mTICI<2b. Postoperative vascular re-occlusion occurred in 3 cases, and symptomatic intracranial hematoma occurred in 6 cases. The NIHSS score at 24 hours after the operation was significantly lower than that on admission, and the NIHSS score was further improved after HBO treatment. Ninety days after the operation, mRS showed 98 cases of good prognoses, while 52 cases of poor prognoses. The levels of HCY and hs-CRP were significantly lower than those before the treatment.Conclusion:Endovascular therapy for acute anterior circulation macrovascular occlusive stroke is safe and effective. Postoperative HBO therapy can significantly improve the prognosis and the quality of life of patients.