BACKGROUND:Antioxidants can alleviate cellular damage and matrix degradation caused by oxidative stress,protect the structure and function of intervertebral discs,and thus delay the occurrence and development of intervertebral disc degeneration.OBJECTIVE:To review the research status of antioxidants in the treatment of intervertebral disc degeneration.METHODS:The first author searched the articles included in CNKI and PubMed databases.The literature search time was from inception to June 2024.Chinese search terms were"intervertebral disc degeneration,antioxidants,oxidative stress,signaling pathways."English search terms were"antioxidants,oxidative stresses,oxidative DNA damage,intervertebral disc degenerations,degenerative disc disease*,disc degeneration*,signal pathway."Finally,92 articles that met the criteria were selected for review.RESULTS AND CONCLUSION:(1)Antioxidants have multiple roles in the treatment of intervertebral disc degeneration,including reducing oxidative stress,inhibiting inflammatory responses,promoting autophagy,inhibiting apoptosis,and protecting the extracellular matrix.Through the combined effect of multiple pathways,antioxidants are expected to become an important means in the treatment of intervertebral disc degeneration.(2)The nano-hydrogel system can quickly and stably target the delivery of antioxidants to the inside of the intervertebral disc and improve the bioavailability of antioxidants.Therefore,the development of new antioxidants and antioxidant combination treatment strategies carried by nano-hydrogel systems will be the focus of future research.

Objective To investigate the distribution and antimicrobial resistance profiles of clinically isolated Haemophilus influenzae and Moraxella catarrhalis in hospitals across China from 2015 to 2021,and provide evidence for rational use of antimicrobial agents.Methods Data of H.influenzae and M.catarrhalis strains isolated from 2015 to 2021 in CHINET program were collected for analysis,and antimicrobial susceptibility testing was performed by disc diffusion method or automated systems according to the uniform protocol of CHINET.The results were interpreted according to the CLSI breakpoints in 2022.Beta-lactamases was detected by using nitrocefin disk.Results From 2015 to 2021,a total of 43 642 strains of Haemophilus species were isolated,accounting for 2.91％of the total clinical isolates and 4.07％of Gram-negative bacteria in CHINET program.Among the 40 437 strains of H.influenzae,66.89％were isolated from children and 33.11％were isolated from adults.More than 90％of the H.influenzae strains were isolated from respiratory tract specimens.The prevalence of β-lactamase was 53.79％in H.influenzae strains.The H.influenzae strains isolated from children showed higher resistance rate than the strains isolated from adults.Overall,779 strains of H.influenzae did not produce β-lactamase but were resistant to ampicillin(BLNAR).Beta-lactamase-producing strains showed significantly higher resistance rates to these antimicrobial agents than the β-lactamase-nonproducing strains.Of the 16 191 M.catarrhalis strains,80.06％were isolated from children and 19.94％isolated from adults.M.catarrhalis strains were mostly susceptible to both amoxicillin-clavulanic acid and cefuroxime,evidenced by resistance rate lower than 2.0％.Conclusions The emergence of antibiotic-resistant H.influenzae due to β-lactamase production poses a challenge for clinical anti-infective treatment.Therefore,it is very important to implement antibiotic resistance surveillance for H.influenzae and guide rational antibiotic use.All local clinical microbiology laboratories should actively improve antibiotic susceptibility testing and strengthen antibiotic resistance surveillance for H.influenzae.

BACKGROUND:Antioxidants can alleviate cellular damage and matrix degradation caused by oxidative stress,protect the structure and function of intervertebral discs,and thus delay the occurrence and development of intervertebral disc degeneration.OBJECTIVE:To review the research status of antioxidants in the treatment of intervertebral disc degeneration.METHODS:The first author searched the articles included in CNKI and PubMed databases.The literature search time was from inception to June 2024.Chinese search terms were"intervertebral disc degeneration,antioxidants,oxidative stress,signaling pathways."English search terms were"antioxidants,oxidative stresses,oxidative DNA damage,intervertebral disc degenerations,degenerative disc disease*,disc degeneration*,signal pathway."Finally,92 articles that met the criteria were selected for review.RESULTS AND CONCLUSION:(1)Antioxidants have multiple roles in the treatment of intervertebral disc degeneration,including reducing oxidative stress,inhibiting inflammatory responses,promoting autophagy,inhibiting apoptosis,and protecting the extracellular matrix.Through the combined effect of multiple pathways,antioxidants are expected to become an important means in the treatment of intervertebral disc degeneration.(2)The nano-hydrogel system can quickly and stably target the delivery of antioxidants to the inside of the intervertebral disc and improve the bioavailability of antioxidants.Therefore,the development of new antioxidants and antioxidant combination treatment strategies carried by nano-hydrogel systems will be the focus of future research.

Objective To investigate the distribution and antimicrobial resistance profiles of clinically isolated Haemophilus influenzae and Moraxella catarrhalis in hospitals across China from 2015 to 2021,and provide evidence for rational use of antimicrobial agents.Methods Data of H.influenzae and M.catarrhalis strains isolated from 2015 to 2021 in CHINET program were collected for analysis,and antimicrobial susceptibility testing was performed by disc diffusion method or automated systems according to the uniform protocol of CHINET.The results were interpreted according to the CLSI breakpoints in 2022.Beta-lactamases was detected by using nitrocefin disk.Results From 2015 to 2021,a total of 43 642 strains of Haemophilus species were isolated,accounting for 2.91％of the total clinical isolates and 4.07％of Gram-negative bacteria in CHINET program.Among the 40 437 strains of H.influenzae,66.89％were isolated from children and 33.11％were isolated from adults.More than 90％of the H.influenzae strains were isolated from respiratory tract specimens.The prevalence of β-lactamase was 53.79％in H.influenzae strains.The H.influenzae strains isolated from children showed higher resistance rate than the strains isolated from adults.Overall,779 strains of H.influenzae did not produce β-lactamase but were resistant to ampicillin(BLNAR).Beta-lactamase-producing strains showed significantly higher resistance rates to these antimicrobial agents than the β-lactamase-nonproducing strains.Of the 16 191 M.catarrhalis strains,80.06％were isolated from children and 19.94％isolated from adults.M.catarrhalis strains were mostly susceptible to both amoxicillin-clavulanic acid and cefuroxime,evidenced by resistance rate lower than 2.0％.Conclusions The emergence of antibiotic-resistant H.influenzae due to β-lactamase production poses a challenge for clinical anti-infective treatment.Therefore,it is very important to implement antibiotic resistance surveillance for H.influenzae and guide rational antibiotic use.All local clinical microbiology laboratories should actively improve antibiotic susceptibility testing and strengthen antibiotic resistance surveillance for H.influenzae.

Targeted regulation of hypoxia inducible factor(HIF)pathway can provide therapeutic basis for inflammatory anemia,hypoxic nephropathy,cardiovascular diseases related to chronic kidney disease and other hypoxic diseases.At present,the first drug to act on the HIF pathway,roxadustat,has been used for the treatment of renal anemia,and other prolyl hydroxylase(PHD)inhibitors are also in clinical research.This article mainly reviews the various pathways and mechanisms of the protective effect of PHD inhibitors on the kidneys.

Objective To monitor the susceptibility of clinical isolates to antimicrobial agents in tertiary hospitals in major regions of China in 2022.Methods Clinical isolates from 58 hospitals in China were tested for antimicrobial susceptibility using a unified protocol based on disc diffusion method or automated testing systems.Results were interpreted using the 2022 Clinical &Laboratory Standards Institute(CLSI)breakpoints.Results A total of 318 013 clinical isolates were collected from January 1,2022 to December 31,2022,of which 29.5％were gram-positive and 70.5％were gram-negative.The prevalence of methicillin-resistant strains in Staphylococcus aureus,Staphylococcus epidermidis and other coagulase-negative Staphylococcus species(excluding Staphylococcus pseudintermedius and Staphylococcus schleiferi)was 28.3％,76.7％and 77.9％,respectively.Overall,94.0％of MRSA strains were susceptible to trimethoprim-sulfamethoxazole and 90.8％of MRSE strains were susceptible to rifampicin.No vancomycin-resistant strains were found.Enterococcus faecalis showed significantly lower resistance rates to most antimicrobial agents tested than Enterococcus faecium.A few vancomycin-resistant strains were identified in both E.faecalis and E.faecium.The prevalence of penicillin-susceptible Streptococcus pneumoniae was 94.2％in the isolates from children and 95.7％in the isolates from adults.The resistance rate to carbapenems was lower than 13.1％in most Enterobacterales species except for Klebsiella,21.7％-23.1％of which were resistant to carbapenems.Most Enterobacterales isolates were highly susceptible to tigecycline,colistin and polymyxin B,with resistance rates ranging from 0.1％to 13.3％.The prevalence of meropenem-resistant strains decreased from 23.5％in 2019 to 18.0％in 2022 in Pseudomonas aeruginosa,and decreased from 79.0％in 2019 to 72.5％in 2022 in Acinetobacter baumannii.Conclusions The resistance of clinical isolates to the commonly used antimicrobial agents is still increasing in tertiary hospitals.However,the prevalence of important carbapenem-resistant organisms such as carbapenem-resistant K.pneumoniae,P.aeruginosa,and A.baumannii showed a downward trend in recent years.This finding suggests that the strategy of combining antimicrobial resistance surveillance with multidisciplinary concerted action works well in curbing the spread of resistant bacteria.

Objective To explore the mechanism of venetoclax(Vene)in the treatment of acute myeloid leukemia(AML).Methods THP1 cells were divided into control group(normal culture),experimental group(100 nmol·L-1 Vene treatment),NC mimics group(100 nmol·L-1 Vene treatment+transfection simulator negative control)and miR-181a mimics group(100 nmol·L-1Vene treated+transfected miR-181a mimic),NC mimics combined with pcDNA3.1-NC group[100 nmol·L-1 Vene treated+transfected mimic negative control+transfected Tyr-3/Trp-5 monooxygenase activation protein gamma(YWHAG)negative control],miR-181a mimics combined with pcDNA3.1-NC group(100 nmol·L-1 Vene treated+transfected miR-181a mimic+transfected YWHAG negative control),Vene+miR-181a mimics+pcDNA3.1-YWHAG group(100 nmol·L-1 Vene treated+transfected miR-181a mimic+transfected pcDNA3.1-YWHAG).Real-time quantitative reverse transcription polymerase chain reaction(qRT-PCR)was used to detect the expression of miR-181a and YWHAG mRNA relative expression level;the positive expression of YWHAG was detected by immunofluorescence;the cell proliferation levels was detected by 5-acetylidene-2'deoxyuracil riboside(EdU)assay;the expression of B-cell lymphoma factor 2(Bel-2)and Bel-2 associated X protein(Bax)were detected by Western blot.Results The relative expression of miR-181a in control group,experimental group,NC mimics group and miR-181a mimics group were 1.00±0.14,0.43±0.05,0.47±0.06 and 0.85±0.11,respectively;the relative mRNA expression level of YWHAG were 1.00±0.16,2.13±0.21,2.35±0.28 and 1.37±0.17,respectively.The above indexes of the experimental group were statistically significant compared with the control group,and the above indexes of the NC mimics group were statistically significant compared with the miR-181a mimics group(all P＜0.01).The relative expression levels of YWHAG in NC mimics combined with pcDNA3.1-NC group,miR-181a mimics combined with pcDNA3.1-NC group,Vene+miR-181a mimics+pcDNA3.1-YWHAG group were 1.00±0.13,0.77±0.10 and 0.93±0.14;the proliferation rates were(18.27±3.55)％,(43.19±7.20)％and(28.41±5.84)％,respectively;the relative expression levels of Bel-2 protein were 1.00±0.19,2.23±0.42 and 1.17±0.25,respectively;the relative expression levels of Bax protein were 1.00±0.17,0.39±0.06 and 0.78±0.11,respectively.The above indexes of miR-181a mimics combined with pcDNA3.1-NC group were compared with those of NC mimics combined with pcDNA3.1-NC group,and the above indexes of Vene+miR-181a mimics+pcDNA3.1-YWHAG group were compared with those of miR-181 a mimics combined with pcDNA3.1-NC group,the differences were statistically significant(all P＜0.05).Conclusion The treatment of Vene in acute myeloid leukemia may be realized by regulating miR-181a targeting YWHAG,thereby inhibiting monocyte proliferation and promoting cell apoptosis.

Objective To monitor the susceptibility of clinical isolates to antimicrobial agents in healthcare facilities in major regions of China in 2023.Methods Clinical isolates collected from 73 hospitals across China were tested for antimicrobial susceptibility using a unified protocol based on disc diffusion method or automated testing systems.Results were interpreted using the 2023 Clinical & Laboratory Standards Institute (CLSI) breakpoints.Results A total of 445199 clinical isolates were collected in 2023,of which 29.0％ were gram-positive and 71.0％ were gram-negative.The prevalence of methicillin-resistant strains in Staphylococcus aureus,Staphylococcus epidermidis and other coagulase-negative Staphylococcus species (excluding Staphylococcus pseudintermedius and Staphylococcus schleiferi) (MRSA,MRSE and MRCNS) was 29.6％,81.9％ and 78.5％,respectively.Methicillin-resistant strains showed significantly higher resistance rates to most antimicrobial agents than methicillin-susceptible strains (MSSA,MSSE and MSCNS).Overall,92.9％ of MRSA strains were susceptible to trimethoprim-sulfamethoxazole and 91.4％ of MRSE strains were susceptible to rifampicin.No vancomycin-resistant strains were found.Enterococcus faecalis had significantly lower resistance rates to most antimicrobial agents tested than Enterococcus faecium.A few vancomycin-resistant strains were identified in both E.faecalis and E.faecium.The prevalence of penicillin-susceptible Streptococcus pneumoniae was 93.1％ in the isolates from children and and 95.9％ in the isolates from adults.The resistance rate to carbapenems was lower than 15.0％ for most Enterobacterales species except for Klebsiella,22.5％ and 23.6％ of which were resistant to imipenem and meropenem,respectively .Most Enterobacterales isolates were highly susceptible to tigecycline,colistin and polymyxin B,with resistance rates ranging from 0.6％ to 10.0％.The resistance rate to imipenem and meropenem was 21.9％ and 17.4％ for Pseudomonas aeruginosa,respectively,and 67.5％ and 68.1％ for Acinetobacter baumannii,respectively.Conclusions Increasing resistance to the commonly used antimicrobial agents is still observed in clinical bacterial isolates.However,the prevalence of important crabapenem-resistant organisms such as crabapenem-resistant K.pneumoniae,P.aeruginosa,and A.baumannii showed a slightly decreasing trend.This finding suggests that strengthening bacterial resistance surveillance and multidisciplinary linkage are important for preventing the occurrence and development of bacterial resistance.

Objective To explore the mechanism of venetoclax(Vene)in the treatment of acute myeloid leukemia(AML).Methods THP1 cells were divided into control group(normal culture),experimental group(100 nmol·L-1 Vene treatment),NC mimics group(100 nmol·L-1 Vene treatment+transfection simulator negative control)and miR-181a mimics group(100 nmol·L-1Vene treated+transfected miR-181a mimic),NC mimics combined with pcDNA3.1-NC group[100 nmol·L-1 Vene treated+transfected mimic negative control+transfected Tyr-3/Trp-5 monooxygenase activation protein gamma(YWHAG)negative control],miR-181a mimics combined with pcDNA3.1-NC group(100 nmol·L-1 Vene treated+transfected miR-181a mimic+transfected YWHAG negative control),Vene+miR-181a mimics+pcDNA3.1-YWHAG group(100 nmol·L-1 Vene treated+transfected miR-181a mimic+transfected pcDNA3.1-YWHAG).Real-time quantitative reverse transcription polymerase chain reaction(qRT-PCR)was used to detect the expression of miR-181a and YWHAG mRNA relative expression level;the positive expression of YWHAG was detected by immunofluorescence;the cell proliferation levels was detected by 5-acetylidene-2'deoxyuracil riboside(EdU)assay;the expression of B-cell lymphoma factor 2(Bel-2)and Bel-2 associated X protein(Bax)were detected by Western blot.Results The relative expression of miR-181a in control group,experimental group,NC mimics group and miR-181a mimics group were 1.00±0.14,0.43±0.05,0.47±0.06 and 0.85±0.11,respectively;the relative mRNA expression level of YWHAG were 1.00±0.16,2.13±0.21,2.35±0.28 and 1.37±0.17,respectively.The above indexes of the experimental group were statistically significant compared with the control group,and the above indexes of the NC mimics group were statistically significant compared with the miR-181a mimics group(all P＜0.01).The relative expression levels of YWHAG in NC mimics combined with pcDNA3.1-NC group,miR-181a mimics combined with pcDNA3.1-NC group,Vene+miR-181a mimics+pcDNA3.1-YWHAG group were 1.00±0.13,0.77±0.10 and 0.93±0.14;the proliferation rates were(18.27±3.55)％,(43.19±7.20)％and(28.41±5.84)％,respectively;the relative expression levels of Bel-2 protein were 1.00±0.19,2.23±0.42 and 1.17±0.25,respectively;the relative expression levels of Bax protein were 1.00±0.17,0.39±0.06 and 0.78±0.11,respectively.The above indexes of miR-181a mimics combined with pcDNA3.1-NC group were compared with those of NC mimics combined with pcDNA3.1-NC group,and the above indexes of Vene+miR-181a mimics+pcDNA3.1-YWHAG group were compared with those of miR-181 a mimics combined with pcDNA3.1-NC group,the differences were statistically significant(all P＜0.05).Conclusion The treatment of Vene in acute myeloid leukemia may be realized by regulating miR-181a targeting YWHAG,thereby inhibiting monocyte proliferation and promoting cell apoptosis.

Objective To monitor the susceptibility of clinical isolates to antimicrobial agents in healthcare facilities in major regions of China in 2023.Methods Clinical isolates collected from 73 hospitals across China were tested for antimicrobial susceptibility using a unified protocol based on disc diffusion method or automated testing systems.Results were interpreted using the 2023 Clinical & Laboratory Standards Institute (CLSI) breakpoints.Results A total of 445199 clinical isolates were collected in 2023,of which 29.0％ were gram-positive and 71.0％ were gram-negative.The prevalence of methicillin-resistant strains in Staphylococcus aureus,Staphylococcus epidermidis and other coagulase-negative Staphylococcus species (excluding Staphylococcus pseudintermedius and Staphylococcus schleiferi) (MRSA,MRSE and MRCNS) was 29.6％,81.9％ and 78.5％,respectively.Methicillin-resistant strains showed significantly higher resistance rates to most antimicrobial agents than methicillin-susceptible strains (MSSA,MSSE and MSCNS).Overall,92.9％ of MRSA strains were susceptible to trimethoprim-sulfamethoxazole and 91.4％ of MRSE strains were susceptible to rifampicin.No vancomycin-resistant strains were found.Enterococcus faecalis had significantly lower resistance rates to most antimicrobial agents tested than Enterococcus faecium.A few vancomycin-resistant strains were identified in both E.faecalis and E.faecium.The prevalence of penicillin-susceptible Streptococcus pneumoniae was 93.1％ in the isolates from children and and 95.9％ in the isolates from adults.The resistance rate to carbapenems was lower than 15.0％ for most Enterobacterales species except for Klebsiella,22.5％ and 23.6％ of which were resistant to imipenem and meropenem,respectively .Most Enterobacterales isolates were highly susceptible to tigecycline,colistin and polymyxin B,with resistance rates ranging from 0.6％ to 10.0％.The resistance rate to imipenem and meropenem was 21.9％ and 17.4％ for Pseudomonas aeruginosa,respectively,and 67.5％ and 68.1％ for Acinetobacter baumannii,respectively.Conclusions Increasing resistance to the commonly used antimicrobial agents is still observed in clinical bacterial isolates.However,the prevalence of important crabapenem-resistant organisms such as crabapenem-resistant K.pneumoniae,P.aeruginosa,and A.baumannii showed a slightly decreasing trend.This finding suggests that strengthening bacterial resistance surveillance and multidisciplinary linkage are important for preventing the occurrence and development of bacterial resistance.