OBJECTIVE To explore the mechanism of Baihe Dihuang decoction in the treatment of Alzheimer's disease(AD) based on network pharmacology, molecular docking and animal experiment. METHODS TCMSP were used to predict the active components and targets of Baihe Dihuang decoction and disease-related targets were collected from GeneCards, OMIM and DRUGBANK databases, respectively. Target protein interactions were analyzed with STRING database and biological function and pathway were analyzed with Metascape database. Lastly relevant results were analyzed with Cytoscape 3.8.0. AutoDock vina software was used for molecular docking to analyze the binding energy of the active components and key targets of Baihe Dihuang decoction. PyMOL software were used to visualize the optimal docking results. ICR male mice were randomly divided into control group, model group, Rolipram group, low, medium and high dose group of Baihe Dihuang decoction. After 14 days of administration, the neurobehavioral scores of mice in each group were collected, and the expression of related proteins in brain tissue was detected, ELISA and Western blotting were used to detect the expression of the key protein cAMP, PKA, p-CREB and BDNF. At last, the adverse reaction of Baihe Dihuang decoction was observed by vomiting experiment. RESULTS A total of 13 active components and 39 key targets were collected from network pharmacology. The docking results showed that the first 10 core targets all performed well and their effects were closely related to PRKACA. Compared with the control group, the model group mice's recognition rate of new objects and the spontaneous alternation reaction rate were significantly reduced, the escape latency was significantly prolonged, and the target quadrant stay time, the number of crossing platforms were significantly reduced; cAMP, PKA, p-CREB and BDNF in the hippocampus of mice was significantly decreased. Baihe Dihuang decoction could reverse the behavior of AD mice and the expression of cAMP, PKA, p-CREB and BDNF. In the vomiting experiment, the anesthesia recovery time of the Rolipram group was significantly prolonged, while that of the Baihe Dihuang decoction group was not significantly affected. CONCLUSION The mechanism of Baihe Dihuang decoction in the treatment of AD may be related to its influence on cAMP-PKA and regulation of cAMP-PKA-CREB-BDNF signal pathway, and the adverse reactions are milder than those of clopramide.

Objective To explore the potential mechanism underlying the treatment of pediatric asthma using Xiaoer Zhixiao Pingchuan Granules through network pharmacology analysis and animal experimental validation.Methods Active components and their associated targets in Xiaoer Zhixiao Pingchuan Granules were identified through screening and retrieval of TCMSP,BATMAN-TCM,and UniProt databases.Disease-related targets for pediatric asthma were selected from GeneCards,DisGeNET,and OMIM databases.The target protein-protein interaction(PPI)relationship between the intersecting targets of the two was obtained through the STRING database,and import it into Cytoscape 3.8.0 software to construct a PPI network.GO and KEGG enrichment analyses were conducted using the Metascape platform to identify potential pathways.An asthmatic mouse model was induced by ovalbumin,and different concentrations of Xiaoer Zhixiao Pingchuan Granules were administered as interventions.Histopathological changes were evaluated using HE staining and PAS staining,and the network pharmacology findings were validated through Western blot analysis.Results A total of 154 active ingredients targeting 283 pediatric asthma-related genes were identified in Xiaoer Zhixiao Pingchuan Granules.KEGG enrichment analyses revealed significant enrichment of signaling pathways such as the PI3K-Akt signaling pathway,TNF signaling pathway,and MAPK signaling pathway among intersection targets.Thirteen key targets were identified through topological analysis of ingredients-targets-pathways network.Animal experiments demonstrated that Xiaoer Zhixiao Pingchuan Granules significantly alleviated ovalbumin-induced airway inflammation and goblet cell hyperplasia,while downregulating the expression of key proteins in the PI3K-Akt signaling pathway(P<0.05).Conclusion The therapeutic efficacy of Xiaoer Zhixiao Pingchuan Granules in pediatric asthma involves a multi-pathway and multi-target mechanism,with the PI3K-Akt signaling pathway emerging as a potential key molecular target.

ObjectiveTo investigate the effects of Jiaohong pills （JHP） and its prescription， Pericarpium Zanthoxyli （PZ） and Rehmanniae Radix （RR） cognitive dysfunction in scopolamine-induced Alzheimer's disease （AD） mice and its mechanism through pharmacodynamic and metabolomics study. MethodThe animal model of AD induced by scopolamine was established and treated with PZ， RG and JHP， respectively. The effects of JHP and its formulations were investigated by open field test， water maze test， object recognition test， avoidance test， cholinergic system and oxidative stress related biochemical test. Untargeted metabolomics analysis of cerebral cortex was performed by ultra-performance liquid chromatography-Quadrupole/Orbitrap high resolution mass spectrometry （UPLC Q-Exactive Orbitrap MS）. ResultThe behavioral data showed that， compared with the model group， the discrimination indexes of the high dose of JHP， PZ and RR groups was significantly increased （P<0.05）. The staging rate of Morris water maze test in the PZ， RR， high and low dose groups of JHP was significantly increased （P<0.05， P<0.01）， the crossing numbers in the PZ， JHP high and low dose groups were significantly increased （P<0.05， P<0.01）； the number of errors in the avoidance test were significantly reduced in the PZ and high-dose JHP groups （P<0.01）， and the error latencies were significantly increased in the JHP and its prescription drug groups （P<0.01）. Compared with the model group， the activities of acetylcholinesterase in the cerebral cortex of the two doses of JHP group and the PZ group were significantly increased （P<0.05， P<0.01）， and the activity of acetylcholinesterase in the high-dose JHP group was significantly decreased （P<0.05）， and the level of acetylcholine was significantly increased （P<0.01）. At the same time， the contents of malondialdehyde in the serum of the two dose groups of JHP decreased significantly （P<0.05， P<0.01）. The results of metabolomics study of cerebral cortex showed that 149 differential metabolites were identified between the JHP group and the model group， which were involved in neurotransmitter metabolism， energy metabolism， oxidative stress and amino acid metabolism. ConclusionJHP and its prescription can antagonize scopolamine-induced cognitive dysfunction， regulate cholinergic system， and reduce oxidative stress damage. The mechanism of its therapeutic effect on AD is related to the regulation of neurotransmitter， energy， amino acid metabolism， and improvement of oxidative stress.

To adapt to the general educational requirements for military academies to prepare for victory under the new situation, the present paper proposed the overall thought of strengthening the post education for military hygiene through analyzing the main problems and causes existing in the current education, combined with the experience and practice of foreign military post education. Moreover, we combined the current situation and reality of post education in military medical universities, and analyzed the corresponding countermeasures from the aspects of teaching staff, course construction, information construction, teaching method and assessment model, expecting to provide guidance and help for better carrying out the post education of military hygiene in the future.

Objective:To explore the efficacy and safety of different anti-platelet regimens in the treatment of high-risk non-disabling ischemic cerebrovascular events (HR-NICE) guided by point-of-care testing of CYP2C19 gene. Methods:A single-centre, prospective, randomised, open-label, and blinded endpoint design was uesd in the study. From July 2020 to January 2022, HR-NICE patients were enrolled in the Stroke Green Channel and Department of Neurology of Xuzhou Central Hospital, and all patients were scraped the buccal mucosa for screening for CYP2C19 loss-of-function allele carriers by point-of-care testing . Patients with intermediate metabolism were defined as those who carried 1 loss-of-function allele and patients with poor metabolism were those who carried 2 loss-of-function alleles. This study reduced the test turnaround time to 1 hour by using a fully automated medical polymerase chain reaction analyzer for a point-of-care test of CYP2C19 genotype. CYP2C19 loss-of-function allele carriers were divided according to the random number table method into the conventional treatment group (clopidogrel 75 mg, once a day), the ticagrelor group (ticagrelor 90 mg, twice a day) and the intensive dose group (clopidogrel 150 mg, once a day) separately combined with aspirin (100 mg, once a day) dual antiplatelet for 21 days. Baseline information, Acute Stroke Org 10172 Treatment Trial staging, 90-day modified Rankin Scale score, occurrence of adverse events and severe adverse events were collected for all the 3 groups. The primary efficacy outcome was new stroke within 90 days, and the primary safety outcome was severe or moderate bleeding within 90 days. Results:A total of 716 patients were included: 240 in the conventional treatment group, 240 in the ticagrelor group and 236 in the intensive dose group. There was no statistically significant difference between the 3 groups at baseline (all P>0.05). There were 26 cases (10.8%) with new stroke events in the conventional treatment group, 11 cases (4.6%) in the ticagrelor group and 4 cases (1.7%) in the intensive dose group, with statistically significant differences among the 3 groups (χ 2=19.28, P<0.05), and the differences between the conventional treatment group and the ticagrelor group (χ 2=6.59, P=0.010) and between the conventional treatment group and the intensive dose group (χ 2=16.83, P<0.001) were statistically significant, whereas the difference between the ticagrelor group and the intensive dose group was not statistically significant ( P>0.05). In the 3 groups, there was 1 case (0.4%) of severe bleeding in the conventional treatment group, 6 cases (2.5%) in the ticagrelor group and none in the intensive dose group, which showed statistically significant differences (χ 2=7.23, P<0.05), and there was statistically significant difference between the ticagrelor group and the intensive dose group ( P=0.030). Among the patients with intermediate CYP2C19 metabolism, there were 13 cases (13/158, 8.2%) with 90-day recurrent stroke in the conventional treatment group, 4 cases (4/153, 2.6%) in the ticagrelor group, and 0 case (0/159) in the intensive dose group, with statistically significant difference (χ 2=16.04, P<0.001), and the differences between the intensive dose group and the conventional treatment group were statistically significant (χ 2=13.64, P<0.001), whereas there was no statistically significant difference between the intensive dose group and the ticagrelor group ( P>0.05). In the patients with 90-day recurrent stroke in the intensive dose group, there was 0 case (0/159) with intermediate metabolism and 4 cases (4/77,5.2%) with poor metabolism, with statistically significant differences ( P=0.011), whereas there were no statistically significant differences in the conventional treatment group and the ticagrelor group ( P>0.05). Conclusions:Screening carriers of CYP2C19 loss-of-function alleles by point-of-care testing can quickly and precisely guide the treatment of patients with non-cardiogenic HR-NICE. An intensive clopidogrel dose of 150 mg, once a day combined with aspirin was effective in reducing stroke recurrence with less occurrence of any bleeding and adverse events, and patients with intermediate CYP2C19 metabolism may be the best population to benefit.

Objective To investigate the efficacy of different doses of clopidogrel combined with aspirin in the treatment of high-risk non-disabling ischaemic cerebrovascular events(HR-NICE)under the precise guidance of point-of-care testing(POCT)of cy-tochrome P-450 2C19(CYP2C19)genotype.Methods The single-center,randomised,prospective,and blinded endpoint assess-ment was used.HR-NICE patients continuously enrolled in the stroke green channel and neurology ward of Xuzhou Central Hospital from January 2021 to January 2022,and all patients scraping of the buccal mucosa will be screened for CYP2C19 loss-of-function allele car-riers by POCT.According to the random number table method,they were divided into the intensive group(clopidogrel 150mg/d)and the conventional group(clopidogrel 75mg/d)combined with aspirin(100mg/d)dual antiplatelet for 21 days.Baseline information,acute stroke Org 10172 treatment trial(TOAST)staging and 90 days modified Rankin scale(mRS)score and occurrence of adverse events and severe adverse events were collected for the two groups.The primary efficacy outcome was new stroke within 90 days and the primary safety outcome was severe or moderate bleeding within 90 days.Results A total of 1301 patients were screened,of which 727 patients carried CYP2C19 loss-of-function allele,and 476 patients were included:236 patients in the intensive group and 240 patients in the conven-tional group.The differences between the two groups were not statistically significant at baseline(P>0.05);4 cases(1.7%)inthein-tensive group and 26 cases(10.8%)in the conventional group had a new stroke at 90 days.The differences between the two groups were statistically significant(χ2 = 16.827,P<0.001);0 case(0)in the intensive group and1 case(2.5%)in the conventional group had moderate to severe haemorrhage at 90 days.The differences between the two groups was not statistically significant(P>0.05).Conclu-sion In HR-NICE patients with CYP2C19 loss-of-function allele,the enhanced clopidogrel dose was more effective than the conven-tional dose in the treatment with the antiplatelet drug aspirin combined with clopidogrel,and had a consistent safety profile with no more adverse events such as bleeding.

Objective: To investigate the analgesic substances in the aerial part of Urtica fissa (Urticae Fissae Herba), commonly used for rheumatoid and rheumatism arthritis. Methods: The analgesic constituents were isolated with the active guidance of hot plate and acetic acid writhing models, and identified by comprehensive spectroscopic analysis. Results: Thirteen alkaloids (1–13), two lignans (14, 15), and three amides (16–18) were isolated from the active fractions. Among them, compound 1 was a new alkaloid, and compound 6 was a new natural product. The activity evaluation in vivo indicated that various pyrrole alkaloids (1, 3, 6, and 12) possessed significant analgesic activities, they could significantly inhibit the mice pain response induced by acetic acid and hot plate at the dosage of 2 mg/kg BW. Conclusion: The study revealed that the pyrrole alkaloids played important roles in the analgesic activities of Urticae Fissae Herba.

Objective:The aims of the study were to investigate the relationship among atherogenic index of plasma (AIP) and inflammatory adipocytokines with the severity of coronary artery calcification (CAC) score in coronary artery disease (CAD). And then we analyzed the diagnostic value of the new markers on CAC.Methods:A total of 241 patients with CAD diagnosed by coronary CT angiography (CTA) and coronary angiography in Baoding First Central Hospital from June 2019 to June 2020 were retrospectively enrolled. According to the presence of calcification in coronary CTA, they were divided into CAC group ( n=63) and non-CAC group ( n=178). The clinical data of the patients were collected, and the levels of serum inflammatory factors were measured by enzyme-linked immunosorbent assay (ELISA). The correlation between CAC score and AIP and inflammatory cytokines was analyzed. The diagnostic value of AIP and inflammatory factors in the formation of CAC in patients with CAD. Results:The levels of AIP, serum osteoprotegerin (OPG) and oligomeric matrix protein (COMP) in CAC group were higher than those in non-CAC group, while the levels of serum fibroblast growth factor 21 (FGF21) were lower than those in non-CAC group, with statistically significant difference (all P<0.01). Correlation analysis showed that CAC score of CAD patients was positively correlated with AIP, OPG and COMP ( r=0.581, 0.451, 0.326, P<0.05), and negatively correlated with FGF21 ( r=-0.294, P<0.05). Receiver operating characteristic (ROC) curve analysis showed that AIP, OPG, COMP and FGF21 had diagnostic value for CAC in CAD patients (all P<0.05). AIP>0.387, OPG>5.150 ng/ml, FGF21>136.35 pg/ml, COMP>733.16 ng/ml were independent factors affecting the formation of CAC (all P<0.05). Conclusions:The increase of AIP and the change of inflammatory factors can be used as markers for the diagnosis of CAC formation in CAD patients.

Background: There is still controversy whether the existence of esophageal heterotopic gastric mucosa (EHGM) and its histological type are related to the laryngopharyngeal symptoms. Aims: To analyze the clinical and histological characteristics of EHGM and its correlation with gastroesophageal reflux. Methods: A retrospective study was conducted in consecutive gastroscopy-proved EHGM cases from September 2018 to January 2020 at the Second Affiliated Hospital of Baotou Medical College. Besides clinical data review and questionnaire survey on reflux symptoms, histological typing of EHGM and immunohistochemistry were also performed in some cases. Results: A total of 1 229 cases of EHGM were recruited. The male-to-female ratio was 1.67:1, and middle-aged people were predominant. Most of the heterotopic mucosa were located 15-18 cm away from the incisors, and were mainly single. Two hundred and ninety-four cases (23.9%) were complicated with reflux esophagitis (RE), of which Los Angeles grade A and B accounted for 96.6%. Regurgitation/acid reflux (15.5 %) and heartburn (12.3%) were the most common esophageal symptoms, while extraesophageal symptoms were rare. Histological typing was obtained in 57 cases, of which, 37 (64.9%) were cardia-type, 18 (31.6%) were fundic-type, and 2 (3.5%) were mixed type. There were no significant differences in gender, age, location and number of EHGM, expression levels of H

Flavaspidic acid AB is a bicyclic phloroglucinol derivative with various biological activities in Dryopteris fragrans (L.) Schott. The structure of flavaspidic acid AB was analyzed by inverse synthesis techniques, and its synthesis was designed under the principle of association. Using phloroglucinol as raw material, the 2-methyl-4-butyrylphloroglucinol was synthesized by Vilsmeier-Haack reaction, reduction and acylation, and the flavaspidic acid fragment was synthesized by acylation, alkylation and deacylation, after which N, N-dimethylmethyleneammonium iodide was activated and the flavaspidic acid AB was obtained. The structures of intermediates and flavaspidic acid AB were confirmed by MS, 1H NMR and 13C NMR, and the yield of the target product reached 14.7%. Results indicate that the designed synthetic route of flavaspidic acid AB is simple and easy.