Objective:To evaluate the effect of electroacupuncture on liver regeneration after partial hepatectomy in mice and the role of the Notch signaling pathway.Methods:Thirty-six SPF healthy male C57BL/6 mice, aged 6 weeks, weighing 20-22 g, were divided into 6 groups ( n=6 each) using a random number table method: sham operation group (group S), partial hepatectomy group (group PH), non-acupoint electroacupuncture+ partial hepatectomy group (group NPH), partial hepatectomy+ Fli-06 group (group PH+ F), acupoint electroacupuncture+ partial hepatectomy group (group EPH), and acupoint electroacupuncture+ partial hepatectomy+ Fli-06 group (group EPH+ F). All the mice except for group S underwent partial hepatectomy. Fli-06 4.8 mg/kg was intraperitoneally injected starting from 2 days before surgery, once a day, until the mice were sacrificed in group PH+ F and group EPH+ F, while the equal volume of 0.9% sodium chloride solution was injected in the other groups. In EPH group, electroacupuncture of bilateral " Zusanli" acupoints lasting for 15 min was performed using continuous waves with a frequency of 2 Hz and an intensity of 1 mA once a day starting from the time point immediately after surgery for 3 consecutive days. Mice were anesthetized at day 2 after partial hepatectomy, and blood samples were taken from the eyeball for determination of the serum alanine transaminase (ALT) and aspartate aminotransferase (AST) concentrations (using a fully automated biochemical analyzer) and concentrations of serum epidermal growth factor (EGF) and hepatocyte growth factor (HGF) (by enzyme-linked immunosorbent assay). The mice were subsequently sacrificed and liver tissues were taken for calculation of the liver mass to body mass ratio and for determination of the expression of liver proliferation marker Ki-67 (by immunohistochemical staining), proliferating cell nuclear antigen (PCNA), cyclin D1 (CCND1), Notch Intracellular Domain (NICD), and hypoxia-inducible factor-1alpha (HIF-1α) (using Western blot) and Notch1, jagged canonical Notch ligand 1 (Jagged1) and hairy and enhancer of split 1 (Hes1) mRNA (by real-time polymerase chain reaction). Results:Compared with group S, the serum ALT, AST, EGF and HGF concentrations were significantly increased, and the expression of hepatic Notch1, Jagged1 and Hes1 mRNA and Ki-67, PCNA, CCND1 and NICD was up-regulated in group PH ( P<0.05 or 0.01). Compared with group PH, the liver mass to body mass ratio and serum EGF and HGF concentrations were significantly increased, the serum ALT and AST concentrations were decreased, and the expression of hepatic Notch1, Jagged1, Hes1 mRNA and Ki-67, PCNA, CCND1, NICD and HIF-1α was up-regulated in group EPH, and the liver mass to body mass ratio and the serum HGF concentrations were significantly decreased, the serum ALT and AST concentrations were increased, and the expression of hepatic Jagged1 and Hes1 mRNA and Ki-67, PCNA, CCND1, NICD, and HIF-1α was down-regulated in group PH+ F ( P<0.05 or 0.01). Compared with group EPH, the liver mass to body mass ratio and serum EGF and HGF concentrations were significantly decreased, the serum ALT and AST concentrations were increased, and the expression of hepatic Notch1, Jagged1, Hes1 mRNA and Ki-67, PCNA, CCND1, NICD and HIF-1α was down-regulated in group EPH+ F ( P<0.01). Conclusions:Electroacupuncture at Zusanli acupoint promotes liver regeneration after partial hepatectomy in mice, and the mechanism may be related to the activation of the Notch signaling pathway.

Objective A serum proteomic approach was used to explore the targets of action of Peitu Qingxin Granules(composed of Rhizoma Atractylodis Macrocephalae,Forsythiae Fructus,Imperatae Rhizoma,Pseudostellariae Radix,etc.)in the treatment of atopic dermatitis.Methods Five patients with atopic dermatitis were selected and treated with Peitu Qingxin Granules for 12 weeks,and five healthy volunteers were used as controls.The clinical core evaluation indexes of atopic dermatitis patients after treatment,including Eczema Area and Severity Index/Scoring Atopic Dermatitis(EASI/SCORAD),Pruritus Score,Patient-Oriented Eczema Measure(POEM),and quality of life index,were assessed.Serum samples were examined using data-independent acquisition-mass spectrometry(DIA-MS)technology,and serum differential proteins between atopic dermatitis patients and healthy people,as well as serum differential proteins in atopic dermatitis patients before and after treatment with Peitu Qingxin Granules were screened according to P＜0.05 and Fold Change>1.2.GO function enrichment analysis and KEGG pathway enrichment analysis were performed on the differential proteins.Results(1)Compared with the pre-treatment period,the clinical core evaluation indexes of patients with atopic dermatitis,including the EASI/SCORAD,Pruritus Score,POEM,and quality-of-life index,were significantly improved after treatment,and the differences were all statistically significant(P＜0.05,P＜0.01).(2)A total of 28 differential proteins were analyzed in the healthy control group and atopic dermatitis group,of which 12 proteins expressions were increased and 16 proteins were decreased,including ALAD(δ-aminolevulinic acid dehydrogenase),LTA4H(leukotriene A-4 hydrolase),CA1(carbonic anhydrase 1),F11(coagulation factor XI),and LCP1(lymphocyte cytoplasmic protein 1),etc..The main signaling pathways involved are PI3K-AKT signaling pathway,lipids and atherosclerosis,ECM-receptor interaction,platelet activation,NF-κB signaling pathway,and neutrophil extracellular trap formation.(3)A total of 12 different proteins were analyzed in atopic dermatitis patients before and after treatment with Peitu Qingxin Granules,of which 8 proteins were increased and 4 proteins were decreased,including ALAD,FGA(fibrinogen α-chain),IGHV3-64D,and IGHV3-38.They were mainly involved in signaling pathways such as lipids and atherosclerosis,complement pathway,Staphylococcus aureus infection,NF-κB signaling pathway,fluid shear stress and atherosclerosis.(4)The expressions of three protein targets including ALAD,FGA and IGHV3-64D,were significantly down-regulated in patients with atopic dermatitis and significantly up-regulated after treatment with Peitu Qingxin Granules.Conclusion The differentially expressed proteins ALAD,FGA and IGHV3-64D may be the action targets of Peitu Qingxin Granules in the treatment of atopic dermatitis,which lays the foundation for further experimental validation.