OBJECTlVE To investigate the myocardiaI toxicity of doxorubicin on the myocardium of rabbits and mechanism. METHODS Doxorubicin 2 mg·kg-1 was injected once a week for eight weeks. After discontinuation of doxorubicin,observation was performed for another 8 weeks. Every weekend, uItrasound examination,cardiac catheterization,angiotensinⅡ(AngⅡ)Western bIotting and pathoIogi-caI examination were performed to anaIyze eject fraction( EF),maximaI rate of rise of Ieft ventricuIar pressure(+dp/ dtmax ),AngⅡexpression IeveI,apoptosis index(AI)and the structure of the myocardium. RESULTS At the 7th injection,EF decreased( P ﹤0.05),but reached the bottom vaIue at the 8th injection. At the 3rd injection,Ieft ventricuIar +dp/ dtmax decreased( P ﹤0.05)and reached the bottom vaIue one week after withdrawaI. After that,it increased and reached a high vaIue six weeks after withd-rowaI. But it was stiII Iower than before administration. At the 2nd injection,AngⅡ expression increased (P﹤0.05). At 1 week after withdrawaI,it reached the top vaIue,but than decreased and reached a Iow vaIue six weeks after withdrowaI,but was stiII higher than before administration. At the 1st injection,AI increased( P ﹤ 0.05). At 1 week after withdrawaI,it reached the top vaIue,but then decreased and reached a Iow vaIue 5 weeks after withdrawaI. But it was stiII higher than before administration. CONCLUSlON Doxorubicin cardiac toxicity can induce an eIevated IeveI of myocardiaI AngⅡ,possibIy associated with increased aIdosterone and myocardiaI tension. Increased Ang Ⅱ may induce further myocardiaI structuraI damage and ventricuIar remodeIing through the ROS and caIcium imbaIance.

BACKGROUND:The repairing of bone defect near joint in long bone resulting from complicated comminuted fracture or excision of bone tumor is very difficult. It is a much studied issue to find a feasible solution to this problem.OBJECTIVE: To explore a feasible treatment to bone defect near joint in long bone through comparative observation of 3 reconstruction methods.DESIGN: A completely randomized experiment with self-control and mutual control.SETTING: Laboratory for Experimental Animals, First Hospital of Jilin University.MATERIALS: Twelve healthy adult hybrid dogs, 5 males and 7 females weighing 12 to 18 kg, were recruited.METHODS: The bone defects near joints were established in upper femoral condyle in the 12 dogs, which were reconstructed by 3 operation styles: only filling with bone cement, filling with bone cement + autogenous ilium bone graft, and filling with bone cement + autogenous ilium bone graft + fixation with L-trapezoid compression plate. There was one dog in each method. The specimens were harvested at the end of weeks 3, 6, 12and 24, respectively, after operation. One week before specimens were harvested the fluorescent labeling was prepared; we conducted vascular perfusion of disulphine blue before the animals were executed.MAIN OUTCOME MEASURES: A series of examinations were carried out, including X-ray film, biomechanical test, intravascular perfusion and tetracycline fluorescent labeling. The bone healing, blood supply recovery and biomechanics were observed in the three groups.RESULTS: The 12 dogs all entered the result analysis. ① Results of Xray examination: Two cases of fracture occurred in experimental side at 6and 12 weeks in group Ⅰ; one case of fracture occurred in experimental side at 6 weeks in group Ⅱ. No fracture happened in group Ⅲ. ② Bone stiffness assayed with biomechanics: It decreased in experimental side as compared to control side by 67% and 70% in group Ⅰ; 66%, 76% and 46% in group Ⅱ; and 8% in group Ⅲ. ③ Specimen observation after operation: Bone formation, callus, and blood supply recovery were significantly better in group Ⅲ than in groups Ⅰ and Ⅱ at all stages.CONCLUSION: The third operation, filling with bone cement + autogenous ilium bone graft + fixation with L-trapezoid compression plate, is an ideal method of bone reconstruction. It can recover bone function, and prevent complications such as refracture and bone nonunion.

To investigate the relationship between the structures of methylhesperetin-7-alkyl ether analogues and their anti-inflammatory activities, nine new compounds, methyl-hesperetin (2), methylhesperetin-7-ethyl ether (3), 7-n-butyl ether (4), 7-n-hexyl ether (5), 7-n-octyl ether (6), 7-n-decyl ether (7), 7-n-dodecyl ether (8), 7-n-tetradecyl ether (9) and 7-n-hexadecyl ether (10), were synthesized with the lead compound of methylhesperidin (1). Their structures were confirmed by UV, 1H NMR, MS and HR-MS spectral data. The in vivo antiinflammatory activities of these compounds were tested on mouse paw edema induced by Freund's complete adjuvant (FCA) and mouse capillary permeability induced by acetic acid with po dose of 300 mg x kg(-1) x d(-1). The result indicated that the anti-inflammatory activities of the synthetic compounds increased firstly and then decreased with the elongating of the length of alkyl chain. After 25-day oral administration of compounds 6, 7 and 8, the inhibitory rates on mouse paw edema of adjuvant arthritis (AA) were 31.9%, 38.5%, 39.1%, respectively. They showed the concentrations of COX-2 in serum of AA mice respectively were 79.3, 75.4, 73.9 ng x L(-1) and the concentrations of PGE2 were in correspondence with 275.4, 258.9, 242.6 ng x L(-1). The inhibitory rates of compounds 6 and 7 on mouse capillary permeability induced by acetic acid were, respectively, 42.4% and 41.5% after 5-day oral administration. Compared with the lead compound of methylhesperidin, the anti-inflammatory activities of compounds 6, 7 and 8 were increased and showed an effective inhibition on the symptom of adjuvant arthritis and capillary permeability in mice.

OBJECTIVE:To study the interaction mechanism between flavonoids and human serum albumin (HSA),and to compare the effects of different B-ring substitutions(hydroxyl,methoxyl group)of flavonoids on macromolecular receptor. METH-ODS:The interaction regularity between three flavonoids with different B-ring substitutions(quercetin,hesperetin,methyl hespere-tin) and HSA was studied with fluorescence spectroscopy,the fluorescence quenching types between 3 flavonoids and HSA were determined and analyzed,and the velated binding constant,binding site and thermodynamic parameters were calculated. RE-SULTS:The quenching constants (Ksv) and binding constants (KA) were decreased with the increase of temperatures. The number of binding site(n)was approximately equal to one,and the thermodynamic parameters ΔH<0,ΔS>0,the binding interaction of these compounds with macromolecules was influenced because of the difference of the B-ring substituents. CONCLUSIONS:The quenching mechanism between three flavonoids and HSA was static quenching;the number of binding site was one;the interaction force of the three compounds with HSA was mainly static electricity,and hydroxyl group in the B-ring was likely the major active group and exerted stronger binding force than methoxyl group to connect with macromolecules.

OBJECTIVE: To explore the effect and mechanism of down-regulating lncRNA TTTY15 targeting miR-4500 on the proliferation, apoptosis, migration and invasion of A172 glioma cells. METHODS: The difference in TTTY15 expression between the glioma cells and tissue was determined with a qRT-PCR method. Complementary binding sites of TTTY15 and miR-4500 were predicted with Starbase software, and the targeting relationship was validated with a luciferase reporter system. A172 glioma cells were divided into Control, si-NC (transfected with control siRNA), si-TTTY15 (transfected with TTTY15 siRNA), si-TTTY15+Anti-miR-NC (co-transfected with TTTY15 siRNA and inhibitor control) and si-TTTY15+Anti-miR-4500 (co-transfected with TTTY15 siRNA and miR-4500 inhibitor) groups. Proliferation, apoptosis, migration and invasion, and the expression of Bax, Bcl-2, MMP-2 and MMP-9 proteins of the A172 glioma cells were respectively detected with CCK-8, flow cytometry, Transwell chamber and Western blotting assays. RESULTS: The expression of TTTY15 in glioma cells and glioma tissues have both increased. The expression levels of TTTY15 and miR-4500 in glioma tissues were inversely correlated. TTTY15 and miR-4500 are mutually targeted. Compared with those of the Control and si-NC groups, the glioma cells in the si-TTTY15 group showed increased level of miR-4500, decreased survival rate, increased apoptosis rate, enhanced cell migration and invasion, increased expression of Bax protein, and decreased expression of Bcl-2, MMP-2 and MMP-9 proteins (P<0.05). Compared with those of the si-TTTY15+Anti-miR-NC group, the A172 glioma cells in the si-TTTY15+Anti-miR-4500 group showed decreased level of miR-4500, increased cell survival rate, decreased apoptosis rate, enhanced cell migration and invasion, decreased expression of Bax protein, and increased expression of Bcl-2, MMP-2, and MMP-9 proteins (P<0.05). CONCLUSION Down-regulating TTTY15 targeting miR-4500 can inhibit the proliferation, migration, invasion and induce apoptosis of the A172 glioma cells.
Apoptosis/genetics* ; Cell Line, Tumor ; Cell Movement/genetics* ; Cell Proliferation ; Down-Regulation ; Gene Expression Regulation, Neoplastic ; Glioma/genetics* ; Humans ; MicroRNAs/genetics* ; RNA, Long Noncoding

Paeonol, quercetin, -sitosterol, and gallic acid extracted from MoutanCortex had been reported to possess anti-oxidative, anti-inflammatory, and antitumoractivities. This work aimed to illustrate the potential anti-oxidative mechanismof monomers in human liver hepatocellular carcinoma (HepG2) cells-induced byhydrogen peroxide (H2O2) and to evaluate whether the hepatoprotective effect ofmonomers was independence or synergy in mice stimulated by carbon tetrachloride(CCl4). Monomers protected against oxidative stress in HepG2 cells in a doseresponsemanner by inhibiting the generation of reactive oxygen species, increasingtotal antioxidant capacity, catalase and superoxide dismutase (SOD) activities, andactivating the antioxidative pathway of nuclear factor E2-related factor 2/KelchlikeECH-associated protein 1 (Nrf2/Keap1) signaling pathway. We found that thein vitro antioxidant capacities of paeonol and quercetin were better than those of-sitosterol and gallic acid. Furthermore, paeonol apparently diminished the levelsof alanine transaminase and aspartate aminotransferase, augmented the contentsof glutathione and SOD, promoted the expressions of Nrf2 and heme oxygenase-1proteins in mice stimulated by CCl4. In HepG2 cells, paeonol, quercetin, -sitosterol,and gallic acid play a defensive role against H2O2-induced oxidative stress throughactivating Nrf2/Keap1 pathway, indicating that these monomers have anti-oxidativeproperties. Totally, paeonol and quercetin exerted anti-oxidative and hepatoprotectiveeffects, which is independent rather than synergy.

Paeonol, quercetin, -sitosterol, and gallic acid extracted from MoutanCortex had been reported to possess anti-oxidative, anti-inflammatory, and antitumoractivities. This work aimed to illustrate the potential anti-oxidative mechanismof monomers in human liver hepatocellular carcinoma (HepG2) cells-induced byhydrogen peroxide (H2O2) and to evaluate whether the hepatoprotective effect ofmonomers was independence or synergy in mice stimulated by carbon tetrachloride(CCl4). Monomers protected against oxidative stress in HepG2 cells in a doseresponsemanner by inhibiting the generation of reactive oxygen species, increasingtotal antioxidant capacity, catalase and superoxide dismutase (SOD) activities, andactivating the antioxidative pathway of nuclear factor E2-related factor 2/KelchlikeECH-associated protein 1 (Nrf2/Keap1) signaling pathway. We found that thein vitro antioxidant capacities of paeonol and quercetin were better than those of-sitosterol and gallic acid. Furthermore, paeonol apparently diminished the levelsof alanine transaminase and aspartate aminotransferase, augmented the contentsof glutathione and SOD, promoted the expressions of Nrf2 and heme oxygenase-1proteins in mice stimulated by CCl4. In HepG2 cells, paeonol, quercetin, -sitosterol,and gallic acid play a defensive role against H2O2-induced oxidative stress throughactivating Nrf2/Keap1 pathway, indicating that these monomers have anti-oxidativeproperties. Totally, paeonol and quercetin exerted anti-oxidative and hepatoprotectiveeffects, which is independent rather than synergy.

Objective:To compare the effectiveness and recurrence rate of different types of mesh or without mesh in laparoscopic hiatal hernia repair.Methods:From Jan 2016 to Mar 2022 at the three hospital 90 patients with hiatal hernia, including 26 cases without mesh, 29 cases using synthetic mesh, and 35 cases using biological mesh underwent laparoscopic hiatal hernia repair.Results:The surgical procedures was successful in all the 90 cases without conversion to open surgeny. There were no statistically significant differences in operative time, intraoperative blood loss and postoperative hospital stay among the three groups ( P>0.05), and there were statistically significant differences in hospital cost between the group without mesh and synthetic mesh and biological mesh ( P<0.05). Long-term follow-up was achieved in 87 patients, with a follow-up rate of 96.7% (87/90), and a median follow-up time of 44 months. There were no significant differences in the incidence of postoperative complications (diarrhea, dysphagia, abdominal distension, chest pain), recurrence rate of symptoms (acid reflux, heartburn) and patient satisfaction among the three groups ( P>0.05). Conclusion:In laparoscopic hiatal hernia repair, the mesh should be carefully selected according to the specific intraoperative situation for a satisfactory clinical efficacy.

Objective:To explore the risk factors of chronic postoperative inguinal pain for laparoscopic trans-abdominal preperitoneal hernia repair and establish a nomogram prediction model for it.Methods:The clinical data of 576 patients who underwent laparoscopic trans-abdominal preperitoneal hernia repair for inguinal pain at the First Hospital of Lanzhou University from January 2015 to December 2020 were analyzed retrospectively. According to different postoperative outcomes, patients were divided into chronic pain group ( n=54) and non-chronic pain group ( n=522), compared two groups of patients in the material, including gender, age, BMI, smoking history, history of drinking, hypertension, diabetes, chronic bronchitis, abdominal surgery history, history of inguinal hernia, hernia type, the hernial sac size, prophylactic use of antibiotics, VAS score, mesh fixation techniques, operation time, length of stay. Measurement data with normal distribution were expressed as ( ± s) and independent sample t test was used for comparison between groups. Measurement data with skewed distribution were expressed as M( Q1, Q3), and the Mann-Whitney U test was used for comparision between groups. Chi-square test was used to compare the measurement data of counting data.Multivariate logistic regression was used to analyze the independent risk factors for chronic postoperative inguinal pain. R software was used to establish the drawing of the nomogram prediction model, and the consistency index, calibration chart and area under the receiver operating characteristic curve was used to evaluate the predictive ability of the nomogram prediction model. Results:According to the results of the Logistic regression analysis, age≤45 years ( OR=2.202, 95% CI: 1.080-4.491), BMI≥24 kg/m 2 ( OR=2.231, 95% CI: 1.204-4.134), hernial sac≤5 cm ( OR=2.623, 95% CI: 1.309-5.257), recurrent hernia ( OR=2.769, 95% CI: 1.118-6.860), preoperative pain ( OR=4.121, 95% CI: 2.004-8.476), suture fixation ( OR=2.204, 95% CI: 1.151-4.219)and Postoperative acute pain (VAS>3) ( OR=5.814, 95% CI: 2.532-13.350) were independent risk factors for chronic postoperative inguinal pain ( P<0.05). Based upon the above independent risk factors, the nomogram prediction model was established and verified. The area under the curve of the nomogram prediction model was 0.779 (95% CI: 0.718-0.840, P<0.01). After internal verification, the concordance index value of the prediction model was 0.779. Conclusion:age≤45 years, BMI ≥24 kg/m 2, hernial sac≤5 cm, recurrent hernia, preoperative pain, suture fixation and Postoperative acute pain (VAS>3) are independent risk factors for chronic postoperative inguinal pain for laparoscopic trans-abdominal preperitoneal hernia repair, the nomogram prediction model has a good accuracy and discrimination with a high value of clinical application.