ObjectiveTo investigate the mechanism of action of Kaixinsan in the treatment of Alzheimer's disease （AD） based on network pharmacology， molecular docking， and animal experimental validation. MethodsThe Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform（TCMSP） and the Encyclopedia of Traditional Chinese Medicine（ETCM） databases were used to obtain the active ingredients and targets of Kaixinsan. GeneCards， Online Mendelian Inheritance in Man（OMIM）， TTD， PharmGKB， and DrugBank databases were used to obtain the relevant targets of AD. The intersection （common targets） of the active ingredient targets of Kaixinsan and the relevant targets of AD was taken， and the network interaction analysis of the common targets was carried out in the STRING database to construct a protein-protein interaction（PPI） network. The CytoNCA plugin within Cytoscape was used to screen out the core targets， and the Metascape platform was used to perform gene ontology（GO） functional enrichment analysis and Kyoto encyclopedia of genes and genomes（KEGG） pathway enrichment analysis. The “drug-active ingredient-target” interaction network was constructed with the help of Cytoscape 3.8.2， and AutoDock Vina was used for molecular docking. Scopolamine （SCOP） was utilized for modeling and injected intraperitoneally once daily. Thirty-two male C57/BL6 mice were randomly divided into blank control （CON） group （0.9% NaCl， n=8）， model （SCOP） group （3 mg·kg^-1·d^-1， n=8）， positive control group （3 mg·kg^-1·d^-1 of SCOP+3 mg·kg^-1·d^-1 of Donepezil， n=8）， and Kaixinsan group （3 mg·kg^-1·d^-1 of SCOP+6.5 g·kg^-1·d^-1 of Kaixinsan， n=8）. Mice in each group were administered with 0.9% NaCl， Kaixinsan， or Donepezil by gavage twice a day for 14 days. Morris water maze experiment was used to observe the learning memory ability of mice. Hematoxylin-eosin （HE） staining method was used to observe the pathological changes in the CA1 area of the mouse hippocampus. Enzyme linked immunosorbent assay（ELISA） was used to determine the serum acetylcholine （ACh） and acetylcholinesterase （AChE） contents of mice. Western blot method was used to detect the protein expression levels of signal transducer and activator of transcription 3（STAT3） and nuclear transcription factor（NF）-κB p65 in the hippocampus of mice. ResultsA total of 73 active ingredients of Kaixinsan were obtained， and 578 potential targets （common targets） of Kaixinsan for the treatment of AD were screened out. Key active ingredients included kaempferol， gijugliflozin， etc.. Potential core targets were STAT3， NF-κB p65， et al. GO functional enrichment analysis obtained 3 124 biological functions， 254 cellular building blocks， and 461 molecular functions. KEGG pathway enrichment obtained 248 pathways， mainly involving cancer-related pathways， TRP pathway， cyclic adenosine monophosphate（cAMP） pathway， and NF-κB pathway. Molecular docking showed that the binding of the key active ingredients to the target targets was more stable. Morris water maze experiment indicated that Kaixinsan could improve the learning memory ability of SCOP-induced mice. HE staining and ELISA results showed that Kaixinsan had an ameliorating effect on central nerve injury in mice. Western blot test indicated that Kaixinsan had a down-regulating effect on the levels of NF-κB p65 phosphorylation and STAT3 phosphorylation in the hippocampal tissue of mice in the SCOP model. ConclusionKaixinsan can improve the cognitive impairment function in SCOP model mice and may reduce hippocampal neuronal damage and thus play a therapeutic role in the treatment of AD by regulating NF-κB p65， STAT3， and other targets involved in the NF-κB signaling pathway.

Objective To explore the roles of iron overload in pro-atherogenic activation of foam cells.Methods RAW264.7 and MOVAS cells were stimulated by oxLDL,ferrimine citrate and deferoxamine respectively.Prussian Blue and Oil Red O staining were used to detect iron deposition and foam cell.CCK-8 test,DHE probe,ELISA,RT-qPCR were performed to detect the cell death rate,reactive oxygen species(ROS)generation,lipid peroxidation molecules[glutathione peroxidase(GSH),glutathione peroxidase 4(GPX4),malondialdehyde(MDA)content]and the mRNA level of ATP binding cassette transporter A1(ABCA1),ATP binding cassette transporter G1(ABCG1),inductible nitris oxide synthase(iNOS),arginase-1(Arg-1),α-smooth muscle actin(α-SMA),smooth muscle 22 alpha(SM22a),osteopontin(OPN),Interleukin-1β(IL-1β),tumor necrosis factor-α(TNF-α).Results Iron overload could reduced reverse cholesterol transporters(ABCA1 and ABCG1),promote foam cells generation,increased cell death rate,induced the expression of lipid peroxidation molecules(GSH,GPX4,MDA),and promoted pro-inflammatory M1 marker of macrophage and synthetic marker expression of vascular smooth muscle cell(VSMC)and inflammatory cytokines(IL-1β,TNF-α).Conclusion Iron overload promotes the generation of foam cells derived from macrophages and smooth muscle cells and transform them into pro-atherosclerotic phenotype,aggravates cell lipid peroxidation and inflammatory reaction,which contributes to the progress of atherosclerosis.

Background: and Purpose: Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is the most-common form of autoimmune encephalitis, but its early diagnosis is challenging.This study aimed to identify the risk factors for a poor prognosis in anti-NMDAR encephalitis and construct a prognostic composite score for obtaining earlier predictions of a poor prognosis. Methods: We retrospectively analyzed the clinical data, laboratory indexes, imaging findings, and electroencephalogram (EEG) data of 60 patients with anti-NMDAR encephalitis. The modified Rankin Scale (mRS) scores of patients were collected when they were discharged from the hospital. The mRS scores were used to divide the patients into two groups, with mRS scores of 3–6 defined as a poor prognosis. Logistic regression analysis was used to analyze independent risk factors related to a poor prognosis. Results: This study found that 23 (38.3%) and 37 (61.7%) patients had good and poor prognoses, respectively. Logistic regression analysis showed that age, disturbance of consciousness at admission, and ≥50% slow waves on the EEG were significantly associated with patient outcomes. An age, consciousness, and slow waves (ACS) composite score was constructed to predict the prognosis of patients with anti-NMDAR encephalitis at an early stage based on regression coefficients. Conclusions Age, disturbance of consciousness at admission, and ≥50% slow waves on the EEG were independent risk factors for a poor prognosis. The ACS prognostic composite score could play a role in facilitating early predictions of the prognosis of anti-NMDAR encephalitis.

Objective: To investigate clinicopathological features, risk of lymph node metastasis, and indications of endoscopic submu-cosal dissection (ESD) in young patients with intramucosal early gastric cancer (EGC). Methods: In total, 325 EGC patients who under-went radical gastrectomy and had complete clinicopathological data in Anhui Provincial Hospital from March 2009 to December 2016 were retrospectively evaluated. All patients were confirmed to have intramucosal cancer based on their postoperative pathology re-sults. The patients were assigned into two groups according to their age: young group (≤40 years) and old group (>40 years). The clini-copathological features and safety of ESD in the youth group were analyzed. Results: Among all patients with intramucosal EGC, 30 (9.2%) were in the youth group. Intramucosal cancer in the youth group occurred predominantly in women, and the pathological types were mainly undifferentiated and mixed, which were more likely to metastasize to the lymph nodes. In the youth group, EGC patients with intramucosal differentiated type, who had ESD indications, had no risk of lymph node metastasis. However, the rate of lymph node metastasis was up to 25% in intramucosal undifferentiated-type EGC patients who had expanded ESD indications. Conclusions:Young patients with intramucosal EGC have poor pathological differentiation and strong invasiveness, and ESD may be considered for the treatment of differentiated intramucosal cancer.

Objective To investigate the effect of prior statin use on outcome after intravenous thrombolysis in patients with acute ischemic stroke. Methods Consecutive patients with acute ischemic stroke treated with intravenous thrombolysis at the Department of Neurology, the Third People's Hospital of Chengdu from July 2014 to August 2017 were enrolled, and divided into the statin use group and nonstatin use group according to prior statin use. Symptomatic intracranial hemorrhage and the outcome at 90 days after onset (good outcome and poor outcome were defined as the modified Rankin Scale score 0-2 and > 2, respectively) in the two groups were compared, and multivariate logistic regression analysis was used to identify the effect of prior statin use on the outcome. Results A total of 327 patients were enrolled, including 68 (20. 80％ ) in the statin use group, and 59 (79. 20％ ) in the nonstatin use group. There were no significant differences in the incidence symptomatic intracranial hemorrhage (7. 35％ vs. 10. 04％; χ2 = 0. 453, P = 0. 501), good outcome rate at 90 days (69. 12％ vs. 66. 02％; χ2 = 0. 232, P = 0. 630), and mortality rate (7. 35％ vs. 7. 34％; P = 1. 000) between the statin use group and the nonstatin use group. Multivariable logistic regression analysis showed that prior statin use were not an independent risk factor for symptomatic intracranial hemorrhage (odds ratio 0. 658, 95％ confidence interval 0. 233-1. 857; P = 0. 429) and poor outcome at 90 dafter onset (odds ratio 0. 848, 95％ confidence interval 0. 424-1. 696; P = 0. 641) in patients treated with intravenous thrombolysis. Conclusion Prior statin use is not associated with symptomatic intracranial hemorrhage and outcome after intravenous thrombolysis in patients with acute ischemic stroke.

Objective To investigate the influences of atrial fibrillation (AF) on clinical outcome and hemorrhagic transformation (HT) after intravenous thrombolysis for acute ischemic stroke.Methods The patients with acute ischemic stroke treated with intravenous recombinant tissue plasminogen activator thrombolysis were enrolled retrospectively.The modified Rankin Scale score 0-2 at 90 d was defined as a good outcome.Multivariate logistic regression analysis was used to determine the correlation between AF and clinical outcomes after intravenous thrombolvsis.Results A total of 160 patients with acute ischemic stroke treated with intravenous recombinant tissue plasminogen activator thrombolysis were enrolled,including 67 (41.88％) with AF.Compared with the non-AF group,the age was older (median [interquartile range] 77 [71-83] years vs.69 [59-78] years;Z=4.142,P＜ 0.001),baseline National Institutes of Health Stroke Scale (NHISS) score was higher (11.0[6.0-17.0] vs.7.0[4.0-14.0];Z=2.623,P=0.009)in the AF group.There were no significant differences in the NIHSS score reduction and the proportion of patients with good outcomes at 24 h (3.0 [1.0-4.5] vs.2.0 [0-6.0];Z=-0.312,P=0.775) and7d(4.0 [2.0-5.0] vs.5.0[2.0-8.0];Z=l.574,P=0.115) after thrombolysis and the proportion of patients with good outcome at 90 d (38.81％ vs.25.82％;x2 =3.063,P =0.080) between the AF group and the non-AF group,however,the proportions of HT within 24 h (14.93％ vs.5.38％;x2 =4.179,P =0.041) and death within 90 days (16.42％ vs.6.45％;x2 =4.073,P =0.044) in the AF group were significantly higher than those in the non-AF group.Multivariate logistic regression analysis showed that AF was not independent correlation with the clinical outcomes at 90 d (odds ratio [OR] 0.950,95％ confidence interval [CI]0.381-2.366;P =0.912),HT within 24 h (OR 1.992,95％ CI0.580-6.369;P =0.285),and death within 90 d (OR 2.483,95％ CI 0.727-8.586;P=0.146).Conclusion AF is not the independent risk factor that influences on clinical outcome at 90 d and-HT within 24 h after intravenous thrombolysis in patients with acute ischemic stroke.

Objective To evaluate surgical approach,safety and efficacy of endoscopic submucosal excavation (ESE) for the treatment of gastric submucosal tumors originated from the muscularis propria layer.Methods Fifty-three patients with submucosal tumors of the stomach diagnosed by gastroscope,were examined using endoscopic ultrasonography (EUS) from February 2012 to April 2013.The patients were completed ESE at general anesthesia.Results The diameter of the tumor was from 5 to 35 mm (median 13.2 mm).The tumors of 48 patients were complete resection,the complete resection rate was 90.6％(48/53).The operation time was from 30 to 150 min (median 45 min).Three patients (5.7％,3/53) had impulsivity hemorrhage during ESE,no patients had unmanageable hemorrhea under the gastroscope.Perforation occurred in 6 patients during ESE,perforation rate was 11.3％ (6/53),the perforation was closed by endoclip in 5 patients.Five patients with inability resection and 1 patient with perforation inability closed were treated with surgical operation.None was developed perforation postoperative and hemorrhea.Conclusion ESE is a safety and efficacy method for treating gastric submucosal tumors originating from the muscularis propria layer.

Paeonol is a major phenolic micromolecular component of Moutan cortex Radicis, a traditional Chinese Medicine. It has shown antitumor effects in previous studies; however, the underlying mechanisms remain unknown. This study investigated the mechanism by giving treatments of placebo, cyclophosphamide, paeonol of 150 and 300 mg/kg to 4 groups of mice bearing EMT6 breast cancer. Apoptosis in tumor cells were confirmed by morphology analysis, including hematoxylin, eosin staining and TUNEL staining. The results showed that the weight of EMT6 breast tumor was significantly reduced in the groups treated with both 150 and 300 mg/kg of paeonol. Immunohistochemical and Western blot results showed that the expression of Bcl-2 was down-regulated while the expression of Bax, caspase 8 and caspase 3 was up-regulated respectively. These results suggest that paeonol exhibits antitumor effects and the mechanism of the inhibition is via induction of apoptosis, regulation of Bcl-2 and Bax expression, and activation of caspase 8 and caspase 3.
Animals ; Apoptosis* ; Blotting, Western ; Breast Neoplasms* ; Caspase 3 ; Caspase 8 ; Cyclophosphamide ; Eosine Yellowish-(YS) ; Hematoxylin ; In Situ Nick-End Labeling ; Medicine, Chinese Traditional ; Mice* ; Phenol

Objective To evaluate the efficacy and safety of endoscopic submucosal excavation in the treatment of suhmucosal tumor.Methods From 2010 to 2013,a total of 108 cases of suhmucosal tumor detected by endoscopic,endoscopic ultrasonography and computed tomography (CT) scan,most of which grew toward the lumen,were treated by endoscopic suhmucosal excavation.After the lesions were completely excavated,pathological examination were performed.All the cases were followed up with endoscopic examination at one,three,six,12 and 24 months after operation.Results Among 108 cases of lesions,27 cases were located in esophagus,eight in cardia,59 in stomach,two in duodenum and 12 cases in rectum.The diameters of the lesions ranged from 0.5 to 5.5 cm (median 2.1 cm).Operation time was between 18 and 240 minutes (median 105 minutes).The endoscopic treatment was converted to laparoscopic operation in three cases because the submucosal tumors of gastric body growing towards outside the lumen,or adhesive to muscular layer tightly and or perforation too big to be sutured.Three cases of submucosal tumor of fundus were failed to excavate,the other 102 cases (94.44％) of lesions were completely removed.Perforation occurred in 19 cases (17.59％).The procedure was converted to laparoscopic operation in one case.Effective endoscopic suture was complered in 18 cases.The volume of haemorrhage during operation was about 0 to 50 mL and no post-operational bleeding was found.Eight cases had cervical subcutaneous emphysema.Nine cases had pneumoperitoneum.Left parotid gland swollen was found in one case.Nine cases were lost to follow up.The left 99 cases were followed up for one to 24 months and no recurrence.Conclusion ndoscopic submucosal excavation safety and effectively achieve once complete removed of the big submucosal tumor which grows towards inside the lumen,and provide complete pathologic data.

ObjectiveTo study the reasons and mechanism of cardiomyocyte apoptosis in chronic heart failure by using Losartan and to provide a theoretical basis for the treatment of chronic heart failure. Methods The models of chronic heart failure were produced by injecting Adriamycin and Losartan as intervention agents, the expression of apoptotic protein Bax, Bcl-2 and channel protein ERK1, JNK1 and P38MAPK were detected by immunohistochemistry and RT-PCR.Cardiomyocyte apoptosis and myocardial ultrastructure are detected by transmission electron microscopy and TUNEL staining.Results Compared with the model group of heart failure, after Losartan treatment, the ultra structure of myocardial cells were significantly improved, Apoptosis index was decreased significantly (P <0.01), The level of Bax and JNK1 decreased (Bax χ~2=6.6149, P=0.0078; JNK1 q=22.0156,P<0.01). However, the expressions of ERK1 and Bcl-2 were significantly increased (ERK1 q=15.3514,P<0.01;Bcl-2 χ~2=6.81,P=0.0074).Conclusion The effect of Losartan on chronic heart failure is related closely with the pathway of ERK1 and JNK1, and no p38 MAPK pathway.