6-gingerol, a bioactive compound from ginger, has demonstrated promising anticancer properties across various cancer models by inducing apoptosis and inhibiting cell proliferation and invasion. In this study, we explore its mechanisms against glioblastoma multiforme (GBM), a notably aggressive and treatment-resistant brain tumor. We found that 6-gingerol crosses the blood-brain barrier more effectively than curcumin, enhancing its potential as a therapeutic agent for brain tumors. Our experiments show that 6-gingerol reduces cell proliferation and triggers apoptosis in GBM cell lines by disrupting cellular energy homeostasis. This process involves an increase in mitochondrial reactive oxygen species (mtROS) and a decrease in mitochondrial membrane potential, primarily due to the downregulation of manganese superoxide dismutase (MnSOD). Additionally, 6-gingerol reduces ERK phosphorylation by inhibiting EGFR and RAF, leading to G1 phase cell cycle arrest. These findings indicate that 6-gingerol promotes cell death in GBM cells by modulating MnSOD and ROS levels and arresting the cell cycle through the ERFR-RAF-1/MEK/ ERK signaling pathway, highlighting its potential as a therapeutic agent for GBM and setting the stage for future clinical research.

6-gingerol, a bioactive compound from ginger, has demonstrated promising anticancer properties across various cancer models by inducing apoptosis and inhibiting cell proliferation and invasion. In this study, we explore its mechanisms against glioblastoma multiforme (GBM), a notably aggressive and treatment-resistant brain tumor. We found that 6-gingerol crosses the blood-brain barrier more effectively than curcumin, enhancing its potential as a therapeutic agent for brain tumors. Our experiments show that 6-gingerol reduces cell proliferation and triggers apoptosis in GBM cell lines by disrupting cellular energy homeostasis. This process involves an increase in mitochondrial reactive oxygen species (mtROS) and a decrease in mitochondrial membrane potential, primarily due to the downregulation of manganese superoxide dismutase (MnSOD). Additionally, 6-gingerol reduces ERK phosphorylation by inhibiting EGFR and RAF, leading to G1 phase cell cycle arrest. These findings indicate that 6-gingerol promotes cell death in GBM cells by modulating MnSOD and ROS levels and arresting the cell cycle through the ERFR-RAF-1/MEK/ ERK signaling pathway, highlighting its potential as a therapeutic agent for GBM and setting the stage for future clinical research.

6-gingerol, a bioactive compound from ginger, has demonstrated promising anticancer properties across various cancer models by inducing apoptosis and inhibiting cell proliferation and invasion. In this study, we explore its mechanisms against glioblastoma multiforme (GBM), a notably aggressive and treatment-resistant brain tumor. We found that 6-gingerol crosses the blood-brain barrier more effectively than curcumin, enhancing its potential as a therapeutic agent for brain tumors. Our experiments show that 6-gingerol reduces cell proliferation and triggers apoptosis in GBM cell lines by disrupting cellular energy homeostasis. This process involves an increase in mitochondrial reactive oxygen species (mtROS) and a decrease in mitochondrial membrane potential, primarily due to the downregulation of manganese superoxide dismutase (MnSOD). Additionally, 6-gingerol reduces ERK phosphorylation by inhibiting EGFR and RAF, leading to G1 phase cell cycle arrest. These findings indicate that 6-gingerol promotes cell death in GBM cells by modulating MnSOD and ROS levels and arresting the cell cycle through the ERFR-RAF-1/MEK/ ERK signaling pathway, highlighting its potential as a therapeutic agent for GBM and setting the stage for future clinical research.

OBJECTIVE To improve the quality standard of Zhuang medicine Yingbupu （Aralia armata）. METHODS A total of 23 batches of Yingbupu （A. armata） were studied. Their macroscopic characteristics and powder microscopic features were observed. TLC was employed for the qualitative identification of oleanolic acid and araloside A. Items such as water content， total ash， acid-insoluble ash， and ethanol-soluble extract were determined according to the methods specified in the 2020 edition of the Chinese Pharmacopoeia （part Ⅳ）. UPLC fingerprint was established for 23 batches of samples by using Similarity Evaluation System for Chromatographic Fingerprints of Traditional Chinese Medicine （2012 edition）， and the contents of oleanolic acid and araloside A were determined. RESULTS The powder microscopic characteristics of the medicinal material were distinctive. Oleanolic acid and araloside A were detected by TLC in all 23 batches. Among the 23 batches of samples， the content ranges of moisture， total ash， acid-insoluble ash， and ethanol-soluble extract were 6.9% to 10.4%， 1.8% to 6.8%， 0.1% to 1.9%， and 2.8% to 8.4%， respectively. Based on the UPLC fingerprint， a total of 15 common peaks were obtained， and 9 of these common peaks were identified. The content ranges of oleanolic acid and araloside A in the 23 batches of samples were 0.86% to 2.69% and 0.16% to 1.10%， respectively. CONCLUSIONS This study has added items such as moisture and total ash content fingerprint， TLC identification. A preliminary quality standard has been established for the medicinal material of Yingbupu （A. armata）， stipulating that the moisture content should not exceed 11.0%， the total ash content should not exceed 5.0%， the acid-insoluble ash content should not exceed 2.5%， the ethanol-soluble extract（No. content should not be less than 4.0%， and the contents of zyyzdxk-2023165） oleanolic acid and araloside A should not be less than 1.00% and 0.45%（ calculated by a dried basis）， respectively.

Objective To investigate the distribution and antimicrobial resistance profiles of the common pathogens isolated from urine from 2015 to 2021 in the CHINET Antimicrobial Resistance Surveillance Program.Methods The bacterial strains were isolated from urine and identified routinely in 51 hospitals across China in the CHINET Antimicrobial Resistance Surveillance Program from 2015 to 2021.Antimicrobial susceptibility was determined by Kirby-Bauer method,automatic microbiological analysis system and E-test according to the unified protocol.Results A total of 261 893 nonduplicate strains were isolated from urine specimen from 2015 to 2021,of which gram-positive bacteria accounted for 23.8％(62 219/261 893),and gram-negative bacteria 76.2％(199 674/261 893).The most common species were E.coli(46.7％),E.faecium(10.4％),K.pneumoniae(9.8％),E.faecalis(8.7％),P.mirabilis(3.5％),P.aeruginosa(3.4％),SS.agalactiae(2.6％),and E.cloacae(2.1％).The strains were more frequently isolated from inpatients versus outpatients and emergency patients,from females versus males,and from adults versus children.The prevalence of ESBLs-producing strains in E.coli,K.pneumoniae and P.mirabilis was 53.2％,52.8％and 37.0％,respectively.The prevalence of carbapenem-resistant strains in E.coli,K.pneumoniae,P.aeruginosa and A.baumannii was 1.7％,18.5％,16.4％,and 40.3％,respectively.Lower than 10％of the E.faecalis isolates were resistant to ampicillin,nitrofurantoin,linezolid,vancomycin,teicoplanin and fosfomycin.More than 90％of the E.faecium isolates were ressitant to ampicillin,levofloxacin and erythromycin.The percentage of strains resistant to vancomycin,linezolid or teicoplanin was＜2％.The E.coli,K.pneumoniae,P.aeruginosa and A.baumannii strains isolated from ICU inpatients showed significantly higher resistance rates than the corresponding strains isolated from outpatients and non-ICU inpatients.Conclusions E.coli,Enterococcus and K.pneumoniae are the most common pathogens in urinary tract infection.The bacterial species and antimicrobial resistance of urinary isolates vary with different populations.More attention should be paid to antimicrobial resistance surveillance and reduce the irrational use of antimicrobial agents.

Objective To understand the distribution and changing resistance profiles of clinical isolates of Enterococcus in hospitals across China from 2015 to 2021.Methods Antimicrobial susceptibility testing was conducted for the clinical isolates of Enterococcus according to the unified protocol of CHINET program by automated systems,Kirby-Bauer method,or E-test strip.The results were interpreted according to the Clinical & Laboratory Standards Institute(CLSI)breakpoints in 2021.WHONET 5.6 software was used for statistical analysis.Results A total of 124 565 strains of Enterococcus were isolated during the 7-year period,mainly including Enterococcus faecalis(50.7％)and Enterococcus faecalis(41.5％).The strains were mainly isolated from urinary tract specimens(46.9％±2.6％),and primarily from the patients in the department of internal medicine,surgery and ICU.E.faecium and E.faecalis strains showed low level resistance rate to vancomycin,teicoplanin and linezolid(≤3.6％).The prevalence of vancomycin-resistant E.faecalis and E.faecium was 0.1％and 1.3％,respectively.The prevalence of linezolid-resistant E.faecalis increased from 0.7％in 2015 to 3.4％in 2021,while the prevalence of linezolid-resistant E.faecium was 0.3％.Conclusions The clinical isolates of Enterococcus were still highly susceptible to vancomycin,teicoplanin,and linezolid,evidenced by a low resistance rate.However,the prevalence of linezolid-resistant E.faecalis was increasing during the 7-year period.It is necessary to strengthen antimicrobial resistance surveillance to effectively identify the emergence of antibiotic-resistant bacteria and curb the spread of resistant pathogens.

Objective To examine the changing antimicrobial resistance profile of Enterobacter spp.isolates in 53 hospitals across China from 2015 t0 2021.Methods The clinical isolates of Enterobacter spp.were collected from 53 hospitals across China during 2015-2021 and tested for antimicrobial susceptibility using Kirby-Bauer method or automated testing systems according to the CHINET unified protocol.The results were interpreted according to the breakpoints issued by the Clinical & Laboratory Standards Institute(CLSI)in 2021(M100 31st edition)and analyzed with WHONET 5.6 software.Results A total of 37 966 Enterobacter strains were isolated from 2015 to 2021.The proportion of Enterobacter isolates among all clinical isolates showed a fluctuating trend over the 7-year period,overall 2.5％in all clinical isolates amd 5.7％in Enterobacterale strains.The most frequently isolated Enterobacter species was Enterobacter cloacae,accounting for 93.7％(35 571/37 966).The strains were mainly isolated from respiratory specimens(44.4±4.6)％,followed by secretions/pus(16.4±2.3)％and urine(16.0±0.9)％.The strains from respiratory samples decreased slightly,while those from sterile body fluids increased over the 7-year period.The Enterobacter strains were mainly isolated from inpatients(92.9％),and only(7.1±0.8)％of the strains were isolated from outpatients and emergency patients.The patients in surgical wards contributed the highest number of isolates(24.4±2.9)％compared to the inpatients in any other departement.Overall,≤ 7.9％of the E.cloacae strains were resistant to amikacin,tigecycline,polymyxin B,imipenem or meropenem,while ≤5.6％of the Enterobacter asburiae strains were resistant to these antimicrobial agents.E.asburiae showed higher resistance rate to polymyxin B than E.cloacae(19.7％vs 3.9％).Overall,≤8.1％of the Enterobacter gergoviae strains were resistant to tigecycline,amikacin,meropenem,or imipenem,while 10.5％of these strains were resistant to polycolistin B.The overall prevalence of carbapenem-resistant Enterobacter was 10.0％over the 7-year period,but showing an upward trend.The resistance profiles of Enterobacter isolates varied with the department from which they were isolated and whether the patient is an adult or a child.The prevalence of carbapenem-resistant E.cloacae was the highest in the E.cloacae isolates from ICU patients.Conclusions The results of the CHINET Antimicrobial Resistance Surveillance Program indicate that the proportion of Enterobacter strains in all clinical isolates fluctuates slightly over the 7-year period from 2015 to 2021.The Enterobacter strains showed increasing resistance to multiple antimicrobial drugs,especially carbapenems over the 7-year period.

Objective To understand the changing distribution and antimicrobial resistance profiles of Proteus,Morganella and Providencia in hospitals across China from January 1,2015 to December 31,2021 in the CHINET Antimicrobial Resistance Surveillance Program.Methods Antimicrobial susceptibility testing was carried out following the unified CHINET protocol.The results were interpreted in accordance with the breakpoints in the 2021 Clinical & Laboratory Standards Institute(CLSI)M100(31 st Edition).Results A total of 32 433 Enterobacterales strains were isolated during the 7-year period,including 24 160 strains of Proteus,6 704 strains of Morganella,and 1 569 strains of Providencia.The overall number of these Enterobacterales isolates increased significantly over the 7-year period.The top 3 specimen source of these strains were urine,lower respiratory tract specimens,and wound secretions.Proteus,Morganella,and Providencia isolates showed lower resistance rates to amikacin,meropenem,cefoxitin,cefepime,cefoperazone-sulbactam,and piperacillin-tazobactam.For most of the antibiotics tested,less than 10％of the Proteus and Morganella strains were resistant,while less than 20％of the Providencia strains were resistant.The prevalence of carbapenem-resistant Enterobacterales(CRE)was 1.4％in Proteus isolates,1.9％in Morganella isolates,and 15.6％in Providencia isolates.Conclusions The overall number of clinical isolates of Proteus,Morganella and Providencia increased significantly in the 7-year period from 2015 to 2021.The prevalence of CRE strains also increased.More attention should be paid to antimicrobial resistance surveillance and rational antibiotic use so as to prevent the emergence and increase of antimicrobial resistance.

Objective To investigate the changing distribution and antibiotic resistance profiles of clinical isolates of Staphylococcus in hospitals across China from 2015 to 2021.Methods Antimicrobial susceptibility testing was conducted for the clinical isolates of Staphylococcus according to the unified protocol of CHINET(China Antimicrobial Surveillance Network)using disk diffusion method and commercial automated systems.The CHINET antimicrobial resistance surveillance data from 2015 to 2021 were interpreted according to the 2021 CLSI breakpoints and analyzed using WHONET 5.6.Results During the period from 2015 to 2021,a total of 204,771 nonduplicate strains of Staphylococcus were isolated,including 136,731(66.8％)strains of Staphylococcus aureus and 68,040(33.2％)strains of coagulase-negative Staphylococcus(CNS).The proportions of S.aureus isolates and CNS isolates did not show significant change.S.aureus strains were mainly isolated from respiratory specimens(38.9±5.1)％,wound,pus and secretions(33.6±4.2)％,and blood(11.9±1.5)％.The CNS strains were predominantly isolated from blood(73.6±4.2)％,cerebrospinal fluid(12.1±2.5)％,and pleural effusion and ascites(8.4±2.1)％.S.aureus strains were mainly isolated from the patients in ICU(17.0±7.3)％,outpatient and emergency(11.6±1.7)％,and department of surgery(11.2±0.9)％,whereas CNS strains were primarily isolated from the patients in ICU(32.2±9.7)％,outpatient and emergency(12.8±4.7)％,and department of internal medicine(11.2±1.9)％.The prevalence of methicillin-resistant strains was 32.9％in S.aureus(MRSA)and 74.1％in CNS(MRCNS).Over the 7-year period,the prevalence of MRSA decreased from 42.1％to 29.2％,and the prevalence of MRCNS decreased from 82.1％to 68.2％.MRSA showed higher resistance rates to all the antimicrobial agents tested except trimethoprim-sulfamethoxazole than methicillin-susceptible S.aureus(MSSA).Over the 7-year period,MRSA strains showed decreasing resistance rates to gentamicin,rifampicin,and levofloxacin,MRCNS showed decreasing resistance rates to gentamicin,erythromycin,rifampicin,and trimethoprim-sulfamethoxazole,but increasing resistance rate to levofloxacin.No vancomycin-resistant strains were detected.The prevalence of linezolid-resistant MRCNS increased from 0.2％to 2.3％over the 7-year period.Conclusions Staphylococcus remains the major pathogen among gram-positive bacteria.MRSA and MRCNS were still the principal antibiotic-resistant gram-positive bacteria.No S.aureus isolates were found resistant to vancomycin or linezolid,but linezolid-resistant strains have been detected in MRCNS isolates,which is an issue of concern.

Objective:To investigate the effects of selinexor,a inhibitor of nuclear export protein 1(XPO1)on the proliferation inhibition and apoptosis of Kasumi-1 cells in acute myeloid leukemia(AML).Methods:MTS method was used to detect the inhibitory effect of different concentrations of selinexor on the proliferation of Kasumi-1 cells at different time points.The apoptosis rate and cell cycle changes after treatment with different concentration of selinexor were detected by flow cytometry.Results:Selinexor inhibited the growth of Kasumi-1 cells at different time points in a concentration-dependent manner(r24 h=0.7592,r48 h=0.9456,and r72 h=0.9425).Selinexor inhibited Kasumi-1 cells growth in a time-dependent manner(r=0.9057 in 2.5 μmol/L group,r=0.9897 in 5 μmol/L group and r=0.9994 in 10 μmol/L group).Selinexor could induce apoptosis of Kasumi-1 cells in a dose-dependent manner(r=0.9732),and the apoptosis of Kasumi-1 cells was more obvious with the increase of drug concentration.The proportion of G0/G1 phase was significantly increased and the proportion of S phase was significantly decreased after the treatment of Kasumi-1 cells by selinexor.With the increase of drug concentration,the proportion of Kasumi-1 cells cycle arrest in G0/G1 phase was increased and the cell synthesis was decreased.Conclusion:Selinexor can promote the death of tumor cells by inhibiting Kasumi-1 cells proliferation,inducing apoptosis and blocking cell cycle.