OBJECTIVE To explore the mechanism of limonin treating in hepatic fibrosis through network pharmacology, and validate its mechanism by molecular docking and animal experiments. METHODS Firstly, the targets of limonin and hepatic fibrosis were screened from the SwissTargetPrediction, GeneCards and DisGeNet database, etc. Meanwhile, the common targets of limonin and hepatic fibrosis were obtained from the bioinformatics website. The protein protein interaction network of common target was constructed by using STRING database and Cytoscape software, and the CytoNCA plug-in was used to screen core targets. And then the enrichment analysis of GO and KEGG on the common target was performed by Metascape database. Thereby, the possible mechanism of limonin against hepatic fibrosis were predicted. Finally, the AutoDock Vina was used for molecular docking verification, and the prediction results of network pharmacology were verified by animal experiments. RESULTS The prediction results indicated that limonin might acted on 86 targets including AKT1, VEGFA and HIF1A, and participated in biological processes including hormone response, protein phosphorylation, angiogenesis, and PI3K-Akt pathway, HIF-1 pathway, VEGF pathway and other signaling pathways related to hepatic fibrosis. The results of protein protein interaction network topology analysis showed that the 11 core targets including AKT1, VEGFA, HIF1A and PIK3CA, etc. Molecular docking results showed that limonin had strong affinity and relatively stable binding conformation with the core targets. In the animal experiments, compared with the model group, hyaluronidase(HA) and laminin(LN) in rat serume in high-dose group of limonin(LH) and low-dose group of limonin(LL)(except for LN in LL group) were declined(P<0.01 or P<0.05), and the degree of inflammation and hepatic fibrosis were relieved to different degrees in liver tissue of the LH group and LL group; Western blotting and qPCR detection showed that protein and mRNA expression levels of AKT, HIF-1α and VEGF(except for VEGF in LL group) was down-regulated in the LH group and LL group(P<0.01 or P<0.05). CONCLUSION Limonin may acts on AKT1, VEGFA, HIF1A and other core targets to treat hepatic fibrosis angiogenesis, which may be related to the inhibition of AKT/HIF-1α/VEGF signaling pathway.

Objective:To investigate the prognosis of liver transplantation (LT) elderly recipients and analyze the influencing factors for prognosis.Methods:The retrospective cohort study was conducted. The clinicopathological data of 400 LT recipients who were admitted to three medical centers from January 2015 to June 2020 were collected, including 368 cases in the First Affiliated Hospital of Zhejiang University School of Medicine, 17 cases in the Affiliated Hangzhou First People's Hospital of Zhejiang University School of Medicine and 15 cases in the Affiliated Hospital of Qingdao University. There were 297 males and 103 females, aged from 22 to 75 years, with a median age of 60 years. Of the 400 LT recipients,200 cases aged ≥60 years were divided into elderly recipients (ER) group and 200 cases aged <60 years were divided into non-elderly recipients (NER) group. Reci-pients underwent orthotopic LT or modified piggyback LT. Observation indicators: (1) survival of recipients and grafts for two groups; (2) influencing factors for death of LT recipients; (3) stratification analysis of ER group. Follow-up using the outpatient examination and telephone interview was conducted to detect survival and prognosis of patients up to May 2021. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the t test. Count data were described as absolute numbers, and comparison between groups was conducted using the chi-square test. Kaplan-Meier method was used to calculate survival rates and draw survival curves. Log-Rank test was used for survival analysis. COX regression model was used for univariate and multivariate analyses. Results:(1) Survival of recipients and grafts for two groups: 400 recipients were followed up for 1 day to 71.7 months, with a median follow-up time of 16.3 months. Survival analysis showed that the 1-, 3-year overall survival rates and 1-, 3-year graft survival rates for ER group were 72.70%, 60.66% and 72.70%, 59.64%, respectively, versus 78.84%, 75.48% and 78.84%, 74.22% for NER group, showing significant differences in the overall survival and graft survival between the two groups ( χ2=5.712, 5.681, P<0.05). (2) Influencing factors for death of LT recipients: results of univariate analysis showed that age, score of model for end stage liver disease, Child-Pugh score, cold ischemia time(CIT) of liver donor, hypertension, blood type of recipients and donors, volume of intraoperative blood loss, volume of intraoperative red blood cell transfusion, volume of intraoperative plasma transfusion, volume of intraoperative crystalloid fluid transfusion, the maximum alanine aminotransferase within postoperative 7 days, the maximum aspartate aminotransferase within postoperative 7 days, total bilirubin were related factors for death of LT recipients ( odds ratio=1.026, 1.022, 1.084, 1.070, 1.701, 2.728, 1.000, 1.056, 1.089, 1.000, 1.000, 1.000, 1.003, 95% confidence interval as 1.006-1.045, 1.005-1.040, 1.060-1.170, 1.011-1.132, 1.133-2.554, 1.701-4.374, 1.000-1.001, 1.031-1.082, 1.039-1.142, 1.000-1.003, 1.001-1.004, 1.000-1.002, 1.001-1.004, P<0.05). Results of multivariate analysis showed that age, blood type of recipients and donors, the maximum aspartate aminotransferase within postoperative 7 days, total bilirubin were independent influencing factors for death of LT recipients ( odds ratio=1.022, 2.761, 1.000, 1.007, 95% confidence interval as 1.001-1.044, 1.612-4.727, 1.000-1.001, 1.002-1.012, P<0.05). (3) Stratification analysis of ER group: ① of 200 recipients in ER group, cases with 0 hour≤CIT≤8 hours, 8 hours12 hours were 96, 73, 31 ,respectively. The 1-year overall survival rates for above recipients were 77.46%, 73.33%, 54.07%, and the 3-year overall survival rates were 62.67%, 65.05%, 41.30%. There was a significant difference in the overall survival between the three groups ( χ2=6.708, P<0.05). ② Of 200 recipients in ER group,182 cases were ABO compatible and 18 were ABO incompatible. The 1-year overall survival rates for above recipients were 77.32%, 27.78%, and the 3-year overall survival rates were 64.63%, 22.22%. There was a significant difference in the overall survival between the two groups ( χ2=23.165, P<0.05). Conclusions:The overall survival of ER is inferior to NER. Age, blood type of recipients and donors, the maximum aspartate aminotransferase within postoperative 7 days, total bilirubin are indepen-dent influencing factors for death of LT recipients. Controlling CIT within 12 hours and avoiding ABO incompatible-liver transplantation can significantly improve the prognosis of ER.

Objective To observe the effects of color retention treatment on the preservation of medicinal plant herbariums, film-cover specimens and resin specimens. Methods Seven kinds of medicinal plants with different characters after color retention treatment were made into herbariums, film-cover specimens and resin specimens, and then the preservation results for the above three kinds of medicinal plant specimens with or without color retention treatment were compared. Results Resin and film-cover specimens without color retention treatment had better preservation results than herbariums. All of the three kinds of specimens with color retention treatment had better preservation results for the original color and shape than the specimens without color retention treatment. Conclusion Color retention treatment for the medicinal plants results into higher preservation quality of the herbariums and longer preservation period.

Objective To investigate the therapeutic effects of erythropoietin sustained-release gelatin hydrogel microspheres (EPO-GHM) on a murine model of hindlimb ischemia and related mechanisms.Methods Fifty two ten weeks old male C57BL/6J mice were assigned to 5 groups:shamoperated group (the right femoral artery suture was passed through the right femoral artery but not tied,n =8);saline group (right femoral artery ligation and intramuscular injection of saline at a dose of 4 ml/kg into the right hind limb,n =12);EPO group(right femoral artery ligation and intramuscular injection of EPO at a dose of 5 000 IU/kg into the right hind limb,n =12),empty GHM group (right femoral artery ligation and intramuscular injection of empty GHM at a dose of 4 ml/kg into the right hind limb,n =8);EPO-GHM group(right femoral artery ligation and intramuscular injection of EPO-GHM at a dose of 5 000 IU/kg into the right hind limb,n =12).The blood flow ratio of ischemic limb (right)/nonischemic limb (left) was measured using a laser Doppler perfusion imager.After 8 weeks,immunohistochemical analysis were used to evaluate the vessel density (vessel density of CD31 positive),arteriole density(vessel density of α-smooth muscle actin(α-SMA) positive) and muscle area(HHF35 positive area).The proliferating index of vessels was evaluated by double immunofluorescent labeling to evaluate effect of EPO-GHM on angiogenesis of ischemia limb.Western blot was used to evaluate the protein expression of EPO receptor,protein kinase B (AKT),p-AKT,endothelial nitric oxide synthase (eNOS),p-eNOS and matrix metalloproteinase 2(MMP-2).Results (1) Eight weeks later,the blood flow ratio of ischemic limb/nonischemic limb was significantly higher in the EPO-GHM group compared with other groups(0.810 ±0.080,0.563 ±0.051,0.570 ±0.056and 0.561 ± 0.052 respectively,all P ＜ 0.05).(2) CD31 antibody positive and α-SAM antibody positive densities were higher in the EPO-GHM group compared with other groups(P ＜ 0.01 or 0.05).(3)HHF35 positive area in saline group,EPO group,empty GHM group and EPO-GHM group were smaller than that of sham-operated group(all P ＜0.05).HHF35 positive area in saline group,EPO group,empty GHM group and EPO-GHM group were similar(all P ＞ 0.05).(4) The proliferating index of vessels was higher in the EPO-GHM group compared with other groups (P ＜ 0.01 or 0.05).(5) Compared with other groups,the protein levels of EPO receptor,AKT,p-AKT,p-eNOS and MMP-2 were significantly higher in EPO-GHM group(P ＜ 0.01 or 0.05) and level of eNOS was similar among five groups (P ＞ 0.05).Conclusion Results from present study suggest EPO-GHM could improve blood perfusion of ischemia limb in mice through increasing capillary and arteriolar densities and these beneficial effects are possibly mediated by EPOR up-regulation and AKT/p-eNOS/MMP-2 signaling pathway activation.

Objective To study the effect of Jingyebaidu granules on treating cytomegalovirus ( CMV) infection during mid-pregnancy. Methods The sexually mature guinea pigs with no CMV infection history served as the subjects. Put the male and female ones in the same cages. Then the female ones were randomly divided into three groups during mid-pregnancy. Model control group:15 guinea pigs which were inoculated 1 mL suspension of GPCMV intraperitoneally. Jingyebaidu Medicine group:15 guinea pigs which were treated with Jingyebaidu(3. 09 mL·kg-1 ) through stomach perfusion after inoculation for 14 days. Normal control group:15 normal mid-pregnant guinea pigs. Viremia rates were examined 7 days after infection. All animals were sacrificed 20 days after infection. The placenta infection rate, pup infection rate, still-born rate were examined. Results Compared with the normal controls, the still-born rate was increased in model control group(8. 33% vs 34. 55%, P<0. 05). In comparison to the model control group, the GPCMV maternal infection rate(86. 67% vs 33. 33%), placenta infection rate (91. 67% vs 61. 22%), pup infection rate(90. 91% vs 48. 28%), still-born rate(34. 55% vs 15. 52%) were significantly decreased in the Jinyebaidu group (all P<0. 05). Conclusion Jinyebaidu granules could reduce maternal infection,pup loss, and placenta infection caused by CMV inoculation during mid-pregnancy.

BACKGROUND:Tranexamic acid is a synthetic anti-fibrinolytic drug, and can effectively control blood loss after total knee arthroplasty through vein. OBJECTIVE:To evaluate the effectiveness and safety of tranexamic acid in reducing blood loss after primary unilateral total knee arthroplasty. METHODS:From 2014 to 2015, 100 patients from the Department of Lower Limb, Sichuan Orthopaedic Hospital underwent primary unilateral total knee arthroplasty, and randomly divided into test group which used tranexamic acid and control group which used tranexamic acid, with 50 cases in each group. 1 g tranexamic acid was infused into the vein at 10 minutes before total knee arthroplasty in the test group, but tranexamic acid was not given in the control group. RESULTS AND CONCLUSION:The amount of total blood loss, postoperative wound drainage in 24 hours, and the amount of blood transfusion were significantly less in the test group than in the control group (P < 0.05). No significant differences in intraoperative blood loss and the number of patients receiving blood transfusion were found between the test and control groups. No significant difference in preoperative hemoglobin levels was detected before surgery, but hemoglobin levels were decreased after surgery between the two groups. Postoperative hemoglobin levels were apparently higher in the test group than in the control group after surgery. At 24 hours after surgery, no significant difference in coagulation was detectable between the two groups. At 6 days, double lower limb vein color Doppler ultrasound examination did not reveal deep vein thrombosis in both groups. These findings verify that treatment with tranexamic acid in the vein before primary unilateral total knee arthroplasty can evidently diminish the amount of perioperative blood loss and blood transfusion, reduce the risk and cost of blood transfusion, which is good for rehabilitation and does not increase the risk of deep vein thrombosis.

Objective To study the therapeutic effect of adjuvant chemotherapy and radiotherapy after operation in patients with mucoepidermoid carcinoma of parotid gland,and to screen the indicators ralated to the prognosis of tumor.Methods Eighty patients with mucoepidermoid carcinoma of parotid gland in First People′Hospital of Yibin of Sichuan Province from January 2005 to December 2009 were analysed retrospectively in our research.We studied the survival of patients who were treated wtih simple operation(30 cases)or postoperative adjuvant therapy(50 cases).Then we further analyzed the relationships between the prognosis of the patients and some variables (age,gender,smoking,alcohol drinking,lymph node metastasis,distant organ metastasis,treat-ment method,differentiation degree and T grading).Results Kaplan-Meier survival curves showed that patients with postoperative adjuvant therapy had longer PFS and OS than those without adjuvant therapy (94.4 months vs 69.3 months;114.9 months vs 96.7 months),with statistical significance (χ2 =11 .246,P =0.001 ;χ2 =15.803,P =0.001 ).COX univariate analysis showed that gender (χ2 =22.346,P =0.000),smoking (χ2 =7.891 ,P =0.041 ),lymph node metastasis (χ2 =12.371 ,P =0.005),distant organ metastasis (χ2 =9.81 3, P =0.002),treatment method (χ2 =25.261 ,P =0.000),differentiation degree (χ2 =4.361 ,P =0.006)and T grading (χ2 =5.336,P =0.01 4)were related to the PFS of patients.COX multivariate analysis showed that lymph node metastasis (χ2 =11 .003,RR =2.827,95%CI:1 .965-3.851 ,P =0.011 ),distant organ metastasis (χ2 =7.611 ,RR =0.472,95%CI:0.240-0.775,P =0.016),treatment method (χ2 =24.542,RR =5.390, 95%CI:3.585-9.602,P =0.000),degree of differentiation (χ2 =3.221 ,RR =2.1 1 8,95%CI:1 .845-4.719, P =0.009)and T grading (χ2 =4.336,RR =0.804,95%CI:0.681 -0.916,P =0.024)were related to the PFS of patients.COX univariate analysis showed that smoking (χ2 =4.551 ,P =0.008),alcohol drinking (χ2 =11 .742,P =0.048),lymph node metastasis (χ2 =14.886,P =0.009),distant organ metastasis (χ2 =6.71 3, P =0.005),treatment method (χ2 =22.411 ,P =0.000),degree of differentiation (χ2 =8.1 16,P =0.012)and T grading (χ2 =14.443,P =0.035)were related to the OS of patients.COX multivariate analysis showed that lymph node metastasis (χ2 =11 .711 ,RR =2.985,95%CI:1 .521 -3.999,P =0.005),distant organ metastasis (χ2 =5.390,RR =0.400,95%CI:0.201 -0.793,P =0.009),treatment method (χ2 =19.327,RR =5.086, 95%CI:3.241 -8.006,P =0.000),degree of differentiation (χ2 =7.084,RR =2.301 ,95%CI:1 .908-4.503, P =0.001 )and T grading (χ2 =1 3.229,RR =0.561 ,95%CI:0.348-0.867,P =0.040)were related to the OS of patients.Conclusion Adjuvant radiation and chemotherapy can obviously prolong the PFS and OS for the patients with mucoepidermoid carcinoma of parotid gland.Lymph node metastasis,distant organ metastasis,treat-ment method,differentiation degree and T grading can greatly influence the prognosis of patients with mucoepider-moid carcinoma of parotid gland,which can be used as independent prognostic indicators for the patients with mucoepidermoid carcinoma of parotid gland.

Objective To compare the effects of peripatellar peripheral nerve partially and totally depolarized in total knee arthroplasty (TKA). Methods 66 TKA patients were divided into partially depolarized group (A, 42 knees) and totally depolarized group (B, 38 knees). The scores of knee-joint, Feller and Visual Analogue Scale were recorded. Results There was no significant difference in all the scores between 2 groups before operation (P>0.05). All the scores improved after operation (P<0.05), however, there was still no significant difference between 2 groups (P>0.05). Conclusion Patellar peripheral nerve partially depolarization technique can reduce postoperative knee pain, which has the same effect with totally depolarization.

Objective To observe the effect of JWSNS serum on proliferation and apoptosis hepatic stellate cells.Methods After being added different concentrations of JWSNS (the low concentrations of JWSNS:0.78 g/ml of crude drug; the medium concentration group of JWSNS:1.56 g/ml of crude drug; the high concentration group of JWSNS:3.12 g/ml of crude drug) drug-containing serum in vitro HSC-T6 cells for 12h,24 h and 48 h respectively,detected serum HSC-T6 proliferation with MTT colorimetry method and measured HSC-T6 apoptosis with flow cytometry and TUNEL method.Results (①) After applied JWSNS on rats HSC-T6,the Cell proliferation was inhibited which showed a time-concentration dependence.The differences were significant when comparing each JWSNS group with the control group (P＜0.01).High concentration of JWSNS group showed significant difference when compared with Biejiaruangan tablets group (P＜0.05) with high concentration of JWSNS (0.399± 0.041) ％ after 48h,and Biejia-Ruangan tablets (0.429± 0.037) ％ after 48 h.② Flow cytometry analysis showed each JWSNS group and Biejiaruangan tablets group had significant increased cell apoptosis when compared with the control group (P＜0.05) after 12 h,24 h,and 48 h.JWSNS medium concentration group [12 h was (17.83±0.25)％,24 h was (26.06±0.26)％,48 h was (39.30±2.25) ％] and JWSNS high concentration group [12 h was (27.15±0.29)％,24 h was (38.96±0.51)％,48 h was (49.34± 0.77) ％] had a significant increased cell apoptosis compared to the Biejia-Ruangan tablets group [ 12 h was (8.31 ± 0.30) ％,24 h was (16.25 ± 0.25) ％,48 h was (27.12± 0.39) ％].③ TUNEL detection showed that each concentration of JWSNS group [the low concentration of JWSNS:was (25.1 ± 1.48)％,medium concentration group of JWSNS was(39.30±2.25)％,high concentration group of JWSNS was(39.30±2.25)％] had a significant increased cell apoptosis rate than Biejiaruangan tablets group (30.0± 3.92) after 48 h (P＜0.01).Conclusion JWSNS containing serum can inhibit the proliferation of HSC-T6 in vitro,promote the apoptosis

A 69-year old female patient was admitted because of 3 days of worsened chest pain.Coronary angiography showed60% stenosis of distal left main stem,chronic total occlusion of left anterior descending (LAD),70% stenosis at the ostium of a smallleft circumflex,70-90%stenosis at the paroxysmal and middle part of a dominant fight coronary artery (RCA),and a normal left internalmammary artery (LIMA) with normal origination and orientation.Percutaneous intervention was attempted but failed on the occludedlesion of LAD.The patient received minimally invasive direct coronary artery bypass (MIDCAB) with left LIMA isolation by Davincirobot.Eleven days later,the RCA lesion was treated by Sirolimus Rapamicin eluting stents implantation percutaneously.Then thepatient was discharged uneventfully after 3 days hospitalization.Our experience suggests that two stop shops of hybrid technique befeasible and safe in the treatment of elderly patient with multiple coronary diseases.