ObjectiveTo investigate the effects of Chaihu and Longgu Mulitang （CLMT） on hippocampal neural damage in the mouse model of depression via the extracellular signal-regulated protein kinase （ERK）/cAMP-response element-binding protein （CREB） signaling pathway. MethodsSeventy-eight male C57BL/6 mice were randomly allocated into normal control， model， low/medium/high-dose （2.89， 5.78， and 11.56 g·kg^-1， respectively） CLMT， and paroxetine （10 mg·kg^-1） groups. A depression model was established by chronic unpredictable mild stress （CUMS） combined with social isolation. Behavioral tests were carried out to evaluate depressive-like behaviors. Hematoxylin-eosin staining and Nissl staining were performed to assess hippocampal morphology and neuronal damage. Immunofluorescence was employed to detect glial fibrillary acidic protein （GFAP） and ionized calcium-binding adapter molecule 1 （Iba1）. Real-time PCR was employed to measure the mRNA levels of ERK and CREB. Western blot was employed to determine the expression of ERK/CREB pathway proteins and brain-derived neurotrophic factor （BDNF） in the hippocampal tissue. Molecular Operating Environment （MOE） software was used for molecular docking to evaluate the interactions between CLMT components and target proteins. ResultsCompared with the normal control group， the model group showed decreased sucrose preference （P0.01）， increased tail-suspension immobility time （P0.01）， decreased activity in the central region of the open field test （P0.01）， and decreased activity in the middle and open-arm region of the elevated plus maze test （P0.01）. The hippocampal area in the model group showed wrinkled cells and a reduction in the number of cells， neurons with reduced sizes and Nissl bodies， enhanced fluorescence intensity of GFAP and Iba1 （P0.01）， and down-regulated expression of phosphorylated （p）-ERK， p-CREB， and BDNF （P0.05， P0.01） and mRNA levels of ERK and CREB （P0.01）. Compared with the model group， the CLMT group showed increased body weight （P0.05， P0.01）， restored cell morphology， with only a small number of ruptured cells， normal neuronal structure and morphology with obvious nuclei and abundant Nissl bodies， weakened fluorescence intensity of GFAP and Iba1 （P0.05， P0.01）， up-regulated mRNA levels of ERK and CREB （P0.05， P0.01） and protein levels of phosphorylated （p）-ERK， p-CREB， and BDNF in the hippocampal tissue （P0.05， P0.01）. The results of molecular docking indicated that nine active ingredients in CLMT had good binding affinity with ERK and CREB. ConclusionCLMT may ameliorate the hippocampal nerve injury in the mouse model of depression by regulating the ERK/CREB pathway.

Objective:To explore the potent effects of denatonium benzoate(DB)on Mas-related G protein-coupled receptor-B2(MrgprB2)-mediated rat mast cell degranulation.Methods:RBL-2H3 cells were treated with DB overnight,before challenged with MrgprB2 ligands substance P(SP).The release of β-hex from MrgprB2-activated RBL-2H3 was detected by substrate method.Detec-tion of LTC4,IL-6,TNF-α and cPLA2 activity were performed by ELISA.The Ca2+influx and the expression of RBL-2H3 MrgprB2 re-ceptors were measured by fluorescence assay.Results:The results showed 10 μmol/L,50 μmol/L,80 μmol/L,100 μmol/L DB treat-ments promoted β-hex and LTC4 releases from activated RBL-2H3,accompanied by increased Ca2+mobilization and cPLA2 activa-tion.DB treatments did not affect IL-6 and TNF-α LTC4 releases in MrgprB2-activated RBL-2H3,as well as the levels of MrgprB2 ex-pression in mast cells.Conclusion:Taken together,DB enhanced the MrgprB2-mediated RBL-2H3 degranulation in vitro,probably by up-regulating Ca2+mobilization in activated cells.

Objective A HPLC-quantitative analysis of multi-components by single marker(QAMS)was established to determine 5 ingredients including uracil,uridine,hypoxanthine,inosine and guanosine in Periplaneta americana.Methods Separation took place on a Agilent ZORBAX SB-Aq column(250 mm×4.6 mm,5 μm)by gradient elution of methanol-0.01 mol·L-1 potassium dihydrogen phosphate at 20℃with a flow rate of 1.0 mL·min-1.The detection wavelength was 260 nm and the injection amount was 10 μL.The relative correction factors(fa/b)was calculated for the other four components with uridine as an internal standard.The content of 5 ingredients in 10 batches of Periplaneta americana was determined by QAMS.Results were compared with those of external standard method(ESM).Results Five nucleosides showed good linear relationships in their own ranges(r＞0.999 5),and the average recoveries ranged from 97.0%to 100.8%.The relative correction factors of uracil,hypoxanthine,inosine and guanosine were 0.908 0,1.005 3,1.969 5 and 1.303 4,respectively.Conclusion The established method is accurate and stable.It can provide theoretical reference for the quality control of Periplaneta americana.

OBJECTIVE To identify the demand levels and specific connotations of pharmaceutical care in social pharmacy based on Kano theory， and to provide suggestions for the optimization of pharmaceutical care in Chinese social pharmacy. METHODS Using Kano theory as the analysis framework， the needs of consumer for different levels of pharmaceutical care in social pharmacy were identified through literature combing. The ideas and suggestions were proposed for the optimization of pharmaceutical care in Chinese social pharmacy based on the content and characteristics of different levels of needs. RESULTS & CONCLUSIONS The demands for pharmaceutical care in Chinese social pharmacy were divided into three levels， among which the basic demand included ensuring the accessibility， safety and effectiveness of drugs； the expectation demand included personalized medication guidance and management， convenient and efficient medication purchasing services triggered by consumer upgrading； the charming demand included health services and management， professional and high-quality service experience. Social pharmacies should take drug security as the core， achieve high quality and good price， and fully meet basic demand； take patient medication management as the grip， conduct double-drive professional services and model innovation to fully respond to expectation demand； take public health as the goal， broaden service content and experience value， and meet the charming demand of consumer at the right time.

ObjectiveTo reveal the targets and molecular mechanisms of the action of Qiangxin Decoction （强心汤） for the treatment of chronic heart failure based on the combination of network pharmacology and molecular docking. MethodsThe active ingredients of Qiangxin Decoction were retrieved from TCMSP database， and the targets of chronic heart failure were screened by searching GeneCards， OMIM， TTD， PharmGkb， and DrugBank databases， and the intersections were taken to obtain the intersecting targets of Qiangxin Decoction for the treatment of chronic heart failure. STRING platform was used to construct the protein-protein interaction network （PPI）， Cytoscape 3.8.0 software was used to calculate the network topology to screen the core targets， and R 4.2.3 was used to construct the “active ingredient-target” network by analyzing the GO enrichment analysis and KEGG pathway enrichment analysis. AutoDock 1.5.7 was used for molecular docking to predict the binding performance of active ingredients and core targets. ResultsSeventy-five intersecting targets were identified for the treatment of chronic heart failure with Qiangxin Decoction， among which the core targets were estrogen receptor 1 （ESR1， degree value=7）， nuclear receptor coactivator 1 （NCOA1， degree value=8）， glucocorticoid receptor （NR3C1， degree value=7）， and nuclear receptor coactivator 2 （NCOA2， degree value=7）. GO enrichment analysis showed that the top 3 items with the smallest P value in molecular function were G protein-coupled amine receptor activity， postsynaptic neurotransmitter receptor activity， and neurotransmitter receptor activity （P＜0.01）； the top 3 items with the smallest P value in biological process were adenylyl cyclase-activated adrenergic receptor signaling pathway， adrenergic receptor signaling pathway， and adenylyl cyclase-regulated G protein-coupled receptor signaling pathway （P＜0.01）； the top 3 items with the smallest P values in cellular composition were components of the postsynaptic membrane， synaptic membrane， and presynaptic membrane （P＜0.01）. KEGG enrichment analysis showed that the top 5 key signaling pathways were neuroactive ligand-receptor interactions， calcium signaling pathway， dopaminergic synapses， cocaine addiction， and cyclic guanosine monophosphate-protein kinase G （cGMP-PKG） signaling pathway. The molecular docking results showed that lignans and isoflavones had lower binding energies and more structural stability with the four core targets （ESR1， NCOA1， NR3C1， NCOA2）. ConclusionThe treatment of chronic heart failure by Qiangxin Decoction was associated with neuroactive ligand-receptor interactions， calcium signaling pathway， dopaminergic synapses， chemoattractant-receptor activation， cGMP-PKG signaling pathway， lipids and atherosclerosis， and cAMP signaling pathway， and lignans and isoflavones may be the core active compounds in its treatment of chronic heart failure.

Objective:To explore the efficacy and safety of treating advanced esophageal cancer by implanting the common stent and the radioactive 125I particle stent with endoscope. Methods:The clinical data of patients with advanced esophageal cancer admitted to Jingbian County People's Hospital of Shaanxi Province, the First Affiliated Hospital of Xi'an Medical University, Xijing Hospital of Digestive Diseases of Air Force Medical University and the First Hospital of Yulin of Shaanxi Province from December 2014 to December 2020 were retrospectively analyzed. Patients were divided into common stent group ( n=66) and radioactive particle stent group ( n=34) according to different stent types. The postoperative complications, Karnofsky performance status (KPS) score, dysphagia score, restenosis rate and quality of life were compared between the two groups. Results:The incidences of postoperative retrosternal pain in the common stent group and the radioactive particle stent group were 65.2% (43/66) and 47.1% (16/34) respectively. The incidences of pharyngeal pain and hoarseness were 12.1% (8/66) and 5.9% (2/34) . The incidences of abdominal pain were 9.1% (6/66) and 2.9% (1/34) . The incidences of errhysis were 3.0% (2/66) and 2.9% (1/34) . The incidences of vomiting and nausea were 7.6% (5/66) and 5.9% (2/34) respectively. There were no statistically significant differences between the two groups ( χ2=3.04, P=0.081; χ2=0.40, P=0.527; χ2=0.53, P=0.467; χ2<0.01, P>0.999; χ2<0.01, P>0.999) . In the two groups, KPS scores in the first, second, third and sixth month after operation were higher than those before operation (all P<0.05) . KPS scores of the radioactive particle stent group in the second, third and sixth month were significantly higher than those of the common stent group [ (89.73±7.84) points vs. (82.37±7.42) points, t=4.62, P<0.001; (93.63±8.13) points vs. (88.33±7.28) points, t=3.74, P<0.001; (92.78±6.26) points vs. (87.28±8.73) points, t=3.77, P<0.001]. The dysphagia scores of patients in the two groups in the first, second, third and sixth month were lower than those before operation (all P<0.05) . The dysphagia scores of the radioactive particle stent group in the third and sixth month after operation were significantly lower than those of the common stent group [ (0.68±0.12) points vs. (2.33±0.32) points, t=26.20, P<0.001; (0.82±0.22) points vs. (2.67±0.24) points, t=36.92, P<0.001]. In the third month after operation, the restenosis rate of the radioactive particle stent group was significantly lower than that of the common stent group [5.88% (2/34) vs. 42.4% (28/66) , χ2 =14.27, P<0.001]. The scores of QLQ-C30 and OES-18 scales in the first, second, third and sixth month after operation were lower than those before operation (all P<0.05) . The scores of QLQ-30 scale in the radioactive particle stent group in the second, third and sixth month were significantly lower than those in the common stent group [ (19.12±3.02) points vs. (21.22±2.87) points, t=3.39, P=0.001; (15.04±1.68) points vs. (20.43±2.23) points, t=12.39, P<0.001; (14.38±2.18) points vs. (19.77±3.67) points, t=9.20, P<0.001]. The scores of OES-18 scale in the radioactive particle stent group were also significantly lower than those in the common stent group [ (17.13±2.07) points vs. (20.64±2.11) points, t=7.95, P<0.001; (15.22±1.88) points vs. (19.24±1.76) points, t=10.62, P<0.001; (14.74±2.36) points vs. (18.53±3.27) points, t=6.01, P<0.001]. Conclusion:The radioactive particle stent can improve the quality of life of patients with advanced esophageal cancer with esophageal stenosis, so as to improve dysphagia and reduce the restenosis rate after operation. However, whether it is obviously superior to common stent in prolonging survival time and reducing complications needs to be further confirmed by a multicenter, prospective, large-sample randomized controlled study.

Objective:To compare the clinical value of stent assisted intestinal bypass and temporary loop ileostomy in laparoscopic low anterior resection of rectal cancer.Method:In this retrospective analysis, 57 patients undergoing laparoscopic low anterior resection for rectal cancer in the First Affiliated Hospital of Ningbo University from Jan 2020 to Jan 2022 were divided into intestinal bypass group (36 cases) and loop ileostomy group (21 cases).Result:There were no significant differences in postoperative GI function recovery and postoperative complication rate between the two groups (all P>0.05). The levels of albumin, prealbumin and hemoglobin in the intestinal bypass group were better than those in the ileostomy group when evaluated on 3rd months after operation [(40.5±2.3) g/L vs. (38.1±2.6)g/L、(26.4±2.7)mg/dl vs. (24.5±2.0)mg/dl、(137.6±5.9) g/L vs. (134.0±7.0) g/L, t=3.605、2.743、2.085, all P<0.05]. Hospital expenses of the intestinal bypass group was lower [(571 000±7 500) yuan vs. (69 300±9 100) yuan, t=-5.477, P<0.05]. Conclusion:Compared with traditional ileostomy, the stent assisted intestinal bypass reduces trauma with lower expenses and improves patients' status after laparoscopic low anterior resection for rectal cancer.

Objective To analyse the differential metabolites and related metabolic pathways in stable angina pectoris of coronary artery heart disease with spleen deficiency and phlegm turbidity syndrome by serum metabolomics.Methods This study observed 60 patients with stable angina pectoris of coronary artery heart disease with spleen deficiency and phlegm turbidity syndrome and 60 healthy volunteers in the same period.Liquid chromatography-mass spectrometry(LC-MS)was performed on the serum metabonomics.The differential metabolites were identified by multivariate statistical analysis of the original spectrogram and original data,and enrichment analysis of KEGG metabolic pathway was analyzed.Results A total of 60 patients in the group of stable angina pectoris of coronary artery heart disease with spleen deficiency and phlegm turbidity syndrome participated in the study,and a total of 60 healthy volunteers in the control group participated in the study.There was no statistical difference in general information and biochemical indicators between the two groups(P>0.05);Eighteen differential metabolites were found respectively,including phenylacetaldehyde,orthophosphate,guanosine,diethyl phosphate,2-dehydro-d-gluconate,guanine and 5-(2-hydroxyethyl)-4-methylthiazole down-regulated expression,taurocholate,2-propylglutaric acid,8-amino-7-oxononanoate,l-tyrosine,s-sulfo-l-cysteine,cyclohexanecarboxylic acid,porphobilinogen,(r)-acetoin,octanoylglucuronide,melatonin and solanine up-regulated expression,involving phenylalanine metabolism,thiamine metabolism,purine metabolism.Conclusion The differential metabolites reveal the metabolic essence of stable angina pectoris of coronary artery heart disease with spleen deficiency and phlegm turbidity syndrome from the micro level,and can provide clues for clinical early warning of patients with stable angina pectoris of coronary artery heart disease with spleen deficiency and phlegm turbidity syndromet.

Objective:To synthesize a novel site-specifically labelled probe 68Ga-1, 4, 7, 10-tetraazacyclododecane-1, 4, 7, 10-tetraacetic acid (DOTA)-Cys-Asp-Val (CDV)-Nb109 and explore its potential for detection of the programmed cell death ligand 1 (PD-L1) expression level in different tumors. Methods:Firstly, CDV was inserted into the tail of the sequence of Nb109 by genetic engineering. Then the precursor DOTA-CDV-Nb109 was prepared by mixing the maleimide-DOTA and the single-domain antibody CDV-Nb109 (amount of substance ratio 1∶1) via the maleimide-cysteine site-specific coupling strategy. Subsequently, the DOTA-CDV-Nb109 was labeled with 68Ga and purified by PD-10 column. Human melanoma A375, human PD-L1 transfected melanoma A375-hPD-L1 and human glioma U87 tumor-bearing mice models were established, and the diagnostic value of 68Ga-DOTA-CDV-Nb109 was evaluated by stability assay, cellular uptake, and microPET imaging. One-way analysis of variance and the least significant difference t test were used to analyze the data. Results:The probe 68Ga-DOTA-CDV-Nb109 was obtained with the radiochemical yield of (69.79±4.69)%, radiochemical purity more than 97%, and molar activity of (12.85±1.51) GBq/μmol. 68Ga-DOTA-CDV-Nb109 had strong binding affinity for A375-hPD-L1 with the dissociation constant ( Kd) of (66.43±17.89) nmol/L. The uptake of 68Ga-DOTA-CDV-Nb109 in A375-hPD-L1 and U87 cells were (3.17±0.15) percentage of the added radioactivity dose (%AD) and (2.08±0.03) %AD respectively, which were significantly higher than that in A375 cells ((1.21±0.14) %AD; F=82.87, t values: 15.23, 9.98, P values: <0.001, 0.003). The tumor uptake of the probe in A375-hPD-L1 ((5.21±0.35) percentage of injected dose per ml (%ID/ml)) and U87 tumor-bearing mice ((3.44±0.69) %ID/ml) were significantly higher than that in A375 tumor-bearing mice ((2.17±0.36) %ID/ml; F=249.72, t values: 35.70, 3.43, both P<0.001). Conclusion:The site-specifically labelled probe 68Ga-DOTA-CDV-Nb109, which can non-invasively and dynamically monitor the change of PD-L1 expression level in different tumors and help screen patients who can benefit from PD-L1 immune checkpoint blocking therapy, is successfully synthesized with high radiochemical purity.

Despite advances in immunotherapy for the treatment of cancers,not all patients can benefit from programmed cell death ligand 1(PD-L1)immune checkpoint blockade therapy.Anti-PD-L1 therapeutic effects reportedly correlate with the PD-L1 expression level;hence,accurate detection of PD-L1 expression can guide immunotherapy to achieve better therapeutic effects.Therefore,based on the high affinity antibody Nb109,a new site-specifically radiolabeled tracer,68Ga-NODA-cysteine,aspartic acid,and valine(CDV)-Nb109,was designed and synthesized to accurately monitor PD-L1 expression.The tracer 68Ga-NODA-CDV-Nb109 was obtained using a site-specific conjugation strategy with a radiochemical yield of about 95％and radiochemical purity of 97％.It showed high affinity for PD-L1 with a dissociation constant of 12.34±1.65 nM.Both the cell uptake assay and positron emission tomography(PET)imaging revealed higher tracer uptake in PD-L1-positive A375-hPD-L1 and U87 tumor cells than in PD-L1-negative A375 tumor cells.Meanwhile,dynamic PET imaging of a NC1-H1299 xenograft indicated that doxorubicin could upregulate PD-L1 expression,allowing timely interventional immunotherapy.In conclusion,this tracer could sensitively and dynamically monitor changes in PD-L1 expression levels in different cancers and help screen patients who can benefit from anti-PD-L1 immunotherapy.