Objective To explore the biological mechanisms of isorhamnetin(ISO)inhibition of breast cancer(BC)progression and effects on paclitaxel sensitivity by in vivo and in vitro experiments.Methods The effects of ISO on MDA-MB-231 cell viability,migration,invasion and apoptosis were explored by CCK-8,scratch,Transwell invasion and apoptosis assays.ISO biological functions were analyzed and core target genes were identified by genome-wide microarrays,functional enrichment and protein-protein interactions(PPI).CYP1B1 expression characterization and prognosis in BC were assessed by quantitative Real-time polymerase chain reaction(qRT-PCR),Western blotting(WB),and Kaplan-Meier plotter database.The effects of CYP1B1 overexpression on MDA-MB-231 cell viability,migration,invasion and apoptosis were explored by CCK-8,scratch,Transwell invasion and apoptosis assays.The effects of ISO and CYP1B1 on BC tumor growth were analyzed by establishing a subcutaneous graft tumor animal model and verified by histological analysis with immunohistochemistry(IHC)and hematoxylin and eosin(HE)staining.The effects of ISO and CYP1B1 on NF-κB signaling were analyzed by qRT-PCR and WB.The effect of ISO combined with paclitaxel on BC progression was analyzed by in vitro and in vivo experiments.Results The results of CCK-8 assay showed that ISO inhibited the viability of MDA-MB-231 cells with an IC50 value of 11.93 μmol/L;the scratch,Transwell invasion and apoptosis assays confirmed that ISO inhibited the migration and invasion of MDA-MB-231 cells and promoted apoptosis(P＜0.05).Volcano plot showed a total of 80 differentially expressed genes(DEGs),of which ISO promoted the expression of 27 genes and inhibited the expression of 53 genes.Gene set enrichment analyses showed that DEGs were mainly enriched in the signaling of organic hydroxyl compound metabolic process,inflammatory response,sterol metabolic process,and nuclear factor-κB(NF-κB).qRT-PCR,WB,and Kaplan-Meier plotter results showed that CYP1B1 mRNA and protein expression was increased in BC and mediated worse prognosis(P＜0.05).CCK-8,scratch,Transwell invasion and apoptosis assays showed that CYP1B1 overexpression enhanced MDA-MB-231 cell viability,migration and invasion,and inhibited apoptosis,which was reversed by the addition of ISO(P＜0.05).The results of in vivo experiments showed that ISO downregulated CYP1B1 expression and attenuated NF-κB signaling(P＜0.05).The results of in vitro and in vivo experiments showed that ISO combined with paclitaxel significantly inhibited BC cell viability and tumor growth(P＜0.05).Conclusion ISO inhibits BC malignant biological behavior by modulating the CYP1B1/NF-κB signaling axis,and ISO enhances paclitaxel sensitivity.

Objective To explore the biological mechanisms of isorhamnetin(ISO)inhibition of breast cancer(BC)progression and effects on paclitaxel sensitivity by in vivo and in vitro experiments.Methods The effects of ISO on MDA-MB-231 cell viability,migration,invasion and apoptosis were explored by CCK-8,scratch,Transwell invasion and apoptosis assays.ISO biological functions were analyzed and core target genes were identified by genome-wide microarrays,functional enrichment and protein-protein interactions(PPI).CYP1B1 expression characterization and prognosis in BC were assessed by quantitative Real-time polymerase chain reaction(qRT-PCR),Western blotting(WB),and Kaplan-Meier plotter database.The effects of CYP1B1 overexpression on MDA-MB-231 cell viability,migration,invasion and apoptosis were explored by CCK-8,scratch,Transwell invasion and apoptosis assays.The effects of ISO and CYP1B1 on BC tumor growth were analyzed by establishing a subcutaneous graft tumor animal model and verified by histological analysis with immunohistochemistry(IHC)and hematoxylin and eosin(HE)staining.The effects of ISO and CYP1B1 on NF-κB signaling were analyzed by qRT-PCR and WB.The effect of ISO combined with paclitaxel on BC progression was analyzed by in vitro and in vivo experiments.Results The results of CCK-8 assay showed that ISO inhibited the viability of MDA-MB-231 cells with an IC50 value of 11.93 μmol/L;the scratch,Transwell invasion and apoptosis assays confirmed that ISO inhibited the migration and invasion of MDA-MB-231 cells and promoted apoptosis(P＜0.05).Volcano plot showed a total of 80 differentially expressed genes(DEGs),of which ISO promoted the expression of 27 genes and inhibited the expression of 53 genes.Gene set enrichment analyses showed that DEGs were mainly enriched in the signaling of organic hydroxyl compound metabolic process,inflammatory response,sterol metabolic process,and nuclear factor-κB(NF-κB).qRT-PCR,WB,and Kaplan-Meier plotter results showed that CYP1B1 mRNA and protein expression was increased in BC and mediated worse prognosis(P＜0.05).CCK-8,scratch,Transwell invasion and apoptosis assays showed that CYP1B1 overexpression enhanced MDA-MB-231 cell viability,migration and invasion,and inhibited apoptosis,which was reversed by the addition of ISO(P＜0.05).The results of in vivo experiments showed that ISO downregulated CYP1B1 expression and attenuated NF-κB signaling(P＜0.05).The results of in vitro and in vivo experiments showed that ISO combined with paclitaxel significantly inhibited BC cell viability and tumor growth(P＜0.05).Conclusion ISO inhibits BC malignant biological behavior by modulating the CYP1B1/NF-κB signaling axis,and ISO enhances paclitaxel sensitivity.

To compare the effects of advanced bone flap and no bone flap on the healing of osteotomy gap in open-wedge high tibial osteotomy (OW-HTO) for the treatment of medial compartment osteoarthritis and knee inversion.Methods:A retrospective study was conducted to analyze the 85 patients who had undergone OW-HTO from March 2021 to December 2021 at Trauma Emergency Centre, The Third Hospital of Hebei Medical University for medial compartment osteoarthritis and knee inversion. The patients were divided into 2 groups according to whether bone flap was grafted. In group A of 42 patients who received advanced bone flap intraoperatively, there were 32 females and 10 males with an age of (63.7±6.6) years; in group B of 43 patients who received no advanced bone flap intraoperatively, there were 31 females and 12 males with an age of (63.2±9.4) years. The measures recorded and compared between the 2 groups included: osteotomy gap healing rates at 3, 6, 12, and 18 months postoperatively; Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), Visual Analog Scale (VAS) for pain, and Knee injury and Osteoarthritis Outcome Score (KOOS) at 6 and 18 months postoperatively; medial proximal tibial angle (MPTA) and femorotibial angle at immediate postoperation and 18 months postoperation; postoperative complications.Results:The differences in preoperative general information between the 2 groups were not statistically significant, showing comparability ( P>0.05). The osteotomy gap healing rates at 3, 6, 12, and 18 months postoperatively in group A were significantly higher than those in group B ( P<0.05). The WOMAC (26.1±5.9), VAS (4.1±1.4), and KOOS (47.0±9.7) scores at 6 months postoperatively in group A were significantly lower than those in group B (31.3±8.3, 4.8±1.6, and 56.1±11.9) ( P<0.05), but the differences in the above indicators between the 2 groups at 18 months postoperatively were not statistically significant ( P>0.05). There was no statistically significant difference in MPTA or femorotibial angle at immediate postoperation between the 2 groups ( P>0.05). At 18 months postoperatively, the MPTA in group A (88.7°±1.1°) was significantly better than that in group B (87.7°±1.5°) ( P<0.05). The total complication rate in group B [27.9% (12/43)] was signifcantly higher than that in group A [2.4% (1/42)]( P<0.05). Conclusions:In the OW-HTO treatment of the patients with medial compartment osteoarthritis and knee inversion, application of an advanced bone flap to fill the osteotomy gap can accelerate the gap healing and reduces occurrence of delayed healing or non-healing of the osteotomy gap.

Objective To investigate the safety of rigid scleral contact lenses in correcting ametropia.Methods A total of 96 patients(192 eyes)with myopia between-20.00 and 0 D and astigmatism between 0 and 3.5 D were included in this perspective study.They were divided into an experimental group(wearing rigid scleral contact lenses)and a control group[wearing rigid corneal contact lenses(RGP)],with 48 patients in each group.Eye indicators including best correc-ted visual acuity(BCVA),corneal endothelial cell density,hexagonal cell ratio,tear film break-up time(BUT),intraocu-lar pressure(IOP),corneal fluorescence staining score,conjunctival congestion score,and ciliary congestion score were measured and compared between the two groups before wearing,on the day of wearing,and 1 week,1 month,and 3 months after wearing lenses,and eye changes were observed.Results The BCVA of patients in the two groups was grea-ter than or equal to 1.00 before wearing lenses and within 3 months after wearing lenses.Compared with before wearing lenses,the corneal endothelial cell density in the experimental group slightly decreased,and the hexagonal cell ratio slightly increased at 3 months after wearing lenses,but the differences were not statistically significant(both P＞0.05).Before wearing lenses and at 3 months after wearing lenses,the corneal endothelial cell density and the hexagonal cell ratio in the experimental group were slightly higher than those in the control group,but the differences were not statistically significant(both P＞0.05).There were no significant differences in BUT and IOP between the experimental group and the control group before wearing,on the day of wearing,and 1 week,1 month,and 3 months after wearing lenses(all P＞0.05).There were no significant differences in corneal fluorescence staining score and conjunctival and ciliary congestion ratings between the experimental group and the control group before wearing lenses and at 3 months after wearing lenses(all P＞0.05).At 3 months after wearing lenses,no conjunctival or corneal edema was observed in the experimental group.Con-clusion Rigid scleral contact lenses and RGP are safe and effective in correcting ametropia;thus,they can be applied widely.

Objective:To investigate the characteristics of attention bias to aggressive information under self-threat priming in college students with different types of high self-esteem.Methods:A total of 650 college students were selected,and high self-esteem participants were selected through the Self Esteem Scale(SES).Then,43 partic-ipants were selected from different types of high self-esteem(fragile and safe)groups through the Implicit Associa-tion Test(IAT).Each group participated in Raven's Standard Progressive Matrices(SPM)with different difficulty levels to complete self-threat priming,and then completed the spatial cue experiment.When the cue was invalid,the attention bias was obtained according to the variation of the reaction time difference(RTI)between the subjects're-sponses to aggressive words and neutral words.Results:The RTI values of the fragile high self-esteem group were higher under high self-threat priming than that of the secure high self-esteem group(P＜0.01).Under low self-threat priming,there was no significant difference in RTI values among different types of high self-esteem groups(P＞0.05).Conclusion:Fragile high self-esteem group are more likely to develop attention bias towards aggressive words under high self-threat priming than that of secure high self-esteem group.

OBJECTIVE To study the imp rovement effects of total flavonoids of Psidium guajava leaves on myocardial hypertrophy in hypertensive model rats. METHODS Ten rats were randomly selected from 60 healthy SD rats as the normal group ； other 50 rats established hypertensive model ，and 44 rats with successful modeling were randomly divided into model group ， anisomycin group [p38 mitogen-activated protein kinase （p38 MAPK）activator，1 mg/kg]，total flavonoids of P. guajava leaves+ anisomycin group （200 mg/kg total flavonoids+ 1 mg/kg anisomycin ）and total flavonoids of P. guajava leaves group （200 mg/kg） by random volume mass ranking method ，with 11 rats in each group. Rats in normal group and model group were given 3％ hydroxymethylcellulose sodium solution ，and other groups were given relevant solution intragastrically ，once a day ，for consecutive 6 weeks. Blood pressure （systolic blood pressure ，diastolic blood pressure ，mean arterial pressure ），cardiac index and left ventricular index were measured. The levels of tumor necrosis factor-α（TNF-α），interleukin-1β（IL-1β）and IL- 6 in myocardial tissue were detected. The pathomorphological changes of myocardial tissue were observed. The expression of p 38 MAPK， phosphorylated p 38 MAPK （p-p38 MAPK），extracellular regulated protein kinase 1/2 （ERK1/2），phosphorylated ERK 1/2 （p-ERK1/2），c-Jun N-terminal kinase （JNK）and phosphorylated JNK （p-JNK）in myocardial tissue were detected. RESULTS Compared with normal group ，the systolic blood pressure ，diastolic blood pressure ，mean arterial pressure ，cardiac index ，left ventricular index as well as the levels of TNF-α，IL-1β and IL-6 and protein expression of p-p 38 MAPK，p-ERK1/2 and p-JNK in myocardial tissue were increased significantly in anisomycin group and model group （P＜0.05）；it was also found that hypertrophy of cardiomyocytes ，disorder of myocardial fibers ，looseness，edema and proliferation of connective tissue between myocardial fibers，increased infiltration of inflammatory cells ，etc. Compared with anisomycin group and model group ，the le vels of above indexes in total flavonoids of P. guajava leaves+ anisomycin group and total flavonoids of P. guajava leaves group were decreased significantly （P＜0.05）； cardiomyocytes were 163.com slightly larger and arranged reasonably ；the degree of myocardial hypertrophy，looseness，edema and proliferation of connective tissue were relieved ，and the improvement effect of total flavonoids of P. guajava leaves group was more significant （P＜0.05）. CONCLUSIONS The total flavonoids of P. guajava leaves can reduce blood pressure and improve myocardial hypertrophy in hypertensive model rats. Its mechanism may be related to the inhibition of p38 MAPK signal pathway activity and the expression of inflammatory factors.

Objective:To optimize the water extraction and alcohol precipitation technology of Xuanfei Zhike granule .Methods:Orthogonal test was used to investigate the effects of adding water , decocting time and boiling time on the water extraction , and the effects of relative density , alcohol precipitation concentration and alcohol precipitation time on the alcohol precipitation technology by taking comprehensive score including the amount of hesperidin , the amount of tectoridin and the yield of dry cream as the indices .Re-sults:The preferred water extraction technology was as follows: added 10 times water and extracted 1.5 h firstly, and then added 8 times water and extracted twice with 0.5 h for each.The preferred alcohol precipitation technology was as follows:concentrated the wa-ter extraction to a relative density of 1.05 (measured at 60℃), slowly added 95％ethanol to 80％alcohol solution and stored 18 h at low temperature .Conclusion:The optimal water extraction and alcohol precipitation technology is stable and feasible , which can pro-vide reference for the standardized production of Xuanfei Zhike granule .

Objective To analyze the influence of general anesthesia (GA) on bilateral subthalamic nucleus deep brain stimulation (STN-DBS) in treating Parkinson's disease (PD) through microelectrode recording (MER),and discuss the differences between different modes of anesthesia.Methods A retrospective analysis was performed on clinical data of 31 PD patients accepted bilateral STN-DBS in our hospital from June 2015 to June 2017.Nine patients accepted surgery under GA (A group):4 patients were treated with intravenous anesthesia (A1 group),and 5 patients were treated with inhalation anesthesia (A2 group);22 patients accepted surgery under local anesthesia LA group.MER indexes,including STN discharge frequency,STN recorded length,and maximum target error,and short-term (6 months) efficacy were recorded.A linear regression analysis was performed to find possible influence factors on discharge frequency and improving rate of UPDRS scores.Results The discharge frequencies of B group,A1 group and A2 group were 51.42 Hz±6.28 Hz,35.79 Hz±7.02 Hz and 43.18 Hz±5.87 Hz,respectively,with significant differences (F=12.181,P=0.000);as compared with that in the B group,the discharge frequencies of A1 group and A2 group were significantly lower (P＜0.05).The STN recorded lengths of B group,A1 group and A2 group were 5.48 mm±0.33 mm,5.06 mm±0.15 mm and 5.22 mam±0.16 mm,respectively,with significant differences (F=4.115,P=0.027);as compared with that in the B group,the recorded lengths of A1 group and A2 group were significantly shorter (P＜0.05).A1 group had the maximum target error,but no significant differences were noted among the 3 groups (P＞ 0.05).Six months after the surgery,the UPDRS-Ⅲ scores and Schwab-England scores of A group and B group were decreased and daily levodopa equivalent (LEDD) was decreased.As compared with B group,A group had significantly better improvement in Hoehn & Yahr grading (P＜0.05).Disease durations were positively correlated with discharge frequency (r=0.539,P=0.002);age and improving rate of UPDRS scores were negatively correlated (r=-0.572,P=-0.001);preoperative LEDD and improving rate of UPDRS scores were positively correlated (r=0.725,P=-0.000).Conclusions Bilateral STN-DBS performed under GA in PD enjoys good efficacy,which shows no obvious difference as compared with that under LA.Inhalation anesthesia had less influence on electrophysiology than intravenous anesthesia.

Objective To investigate the expression of oxidative stress related factors,such as,superoxide dismutase (SOD),heme oxygenase-1 (HO-1),malondialdehyde (MDA) and 8-hydroxy-2'-deoxyguanosine (8-OHdG) in patients with idiopathic membranous nephropathy (IMN) and explore the possible role of oxidative stress in the pathogenesis of IMN.Methods Serum,urine and renal tissue of 40 patients with IMN,20 patients with secondary membranous nephropathy (SMN),and 20 patients with minimal change nephropathy (MCD) were collected from the nephrology department of the First Affiliated Hospital of Zhengzhou University.All of them were diagnosed by renal biopsy from January 2016 to June 2016.Serum,urine and renal tissue of 20 healthy persons were collected as the normal control (NC).The expressions of SOD,HO-1,and 8-OHdG in renal tissues were detected by immunohistochemistry.The levels of SOD,HO-1,MDA and 8-OHdG in serum and urine specimens were detected by ELISA.The relationship between oxidative stress related factors and proteinuria in IMN was investigated as well.Results The expressions of SOD,HO-1 and 8-OHdG were significantly higher than those in MCD group and NC group in renal tissue;the expression of SOD in IMN group was significantly higher than that in MCD group and NC group in serum (all P ＜ 0.01).The expressions of HO-1,MDA and 8-OHdG in the serum and urine of the IMN group were significantly higher than those of the MCD group and the NC group (all P ＜ 0.05).There was a significant positive correlation between the urine expression of 8-OHdG and MDA and proteinuria in the IMN group.Conclusions Oxidative stress-related factors in IMN patients are elevated,which is closely related to clinical manifestations.In that sense,it is confirmed that oxidative stress is involved in the pathogenesis of IMN.

Objective:To illustrate the effect and mechanism of ibrutinib,a Bruton's tyrosine kinase(BTK)inhibitor that inhibits diffuse large B-cell lymphoma(DLBCL)cell survival.Methods:DLBCL cell lines SUDHL-10 and HBL-1 were treated with ibrutinib at different concentrations.A MTT assay was used to detect the inhibition of cell proliferation.Cell apoptosis was analyzed by Annexin V-binding assay,as well as flow cytometry and DAPI staining.The expression of phosphorylated BTK,AKT and ERK was detected by Western blot. DLBCL cells were co-cultured with MSC.The inhibitory effect of ibrutinib on DLBCL cells in tumor microenvironment was assessed in clonogenicity in vitro and in a tumor-bearing non-obese diabetic/severe combined immunodeficient mice in vivo.Results:Up to 2.5 μmol/L and high concentrations of ibrutinib significantly inhibited the proliferation of DLBCL cells in a dose-dependent manner.Approx-imately 1 and 2.5 μmol/L ibrutinib was added on SUDHL-10 cells for 24 h,and the cell apoptotic rates were(21.73±3.64)% and(34.71± 2.36)%,respectively.Both were superior to that of the control group(3.55±1.89)%(P<0.05).Both two DLBCL cell lines pretreated with 5 and 10 μmol/L ibrutinib for 24 h and exhibited nuclear shrinkage at 5 μmol/L and nuclear fragmentation at 10 μmol/L.The expres-sion of phosphorylated BTK,AKT,and ERK decreased significantly after ibrutinib treatment.Ibrutinib inhibited clonogenicity in vitro(P<0.01)and cell proliferation and growth in vivo of DLBCL cells in co-culture system.The differences were statistically significant.Conclu-sion:Ibrutinib can inhibit the proliferation and induce apoptosis of SUDHL-10 and HBL-1 cell lines through a mechanism of blocking the AKT and ERK signaling pathways,as well as the proliferation of DLBCL cells in tumor microenvironment.This finding can significant-ly benefit DLBCL treatment.