Objective:To analyze the drug resistance status of Mycobacterium tuberculosis（MTB）at a hospital in Xiamen over the past decade. Methods:Sputum culture-positive specimens of tuberculosis patients from Xiamen Xinglin Hospital from 2015 to 2024 were collected retrospectively. Isolates were identified as MTB complex and subjected to drug susceptibility testing. Drug resistance patterns and trends over the study period were analyzed using descriptive statistics and Chi-square trend tests in SPSS 27.0 and GraphPad Prism 8.0.Results:Among 3 883 MTB isolates analyzed，1 132（29.15%）exhibited resistance to at least one drug. The highest rates of resistance to individual first-line drugs were observed for isoniazid（INH，16.04%），streptomycin（SM，15.43%），and rifampicin（RFP，12.28%）. Multidrug-resistant tuberculosis（MDR-TB）was identified in 380 isolates（9.79%）. The predominant MDR resistance patterns were INH+RFP+SM（2.34%），INH+RFP（1.65%），and INH+RFP+SM+ethambutol（EMB）（1.03%）. Polyresistance was found in 188 isolates（4.84%），the predominant patterns were INH+SM（1.49%），INH+fluoroquinolone（FQs）（0.31%），and INH+para-aminosalicylic acid（PAS）（0.31%）. Extensively drug-resistant tuberculosis（XDR-TB）was detected in 49 isolates（1.26%）. From 2015 to 2024，significant decreasing trends were observed for overall drug resistance（ χ2=8.858， P=0.003），MDR（ χ2=15.692， P<0.001），and RFP resistance（ χ2=21.627， P<0.001）. In contrast，fluoroquinolone（FQs）resistance showed no significant trend（ χ2=0.149， P=0.699）. Among RFP resistant and MDR isolates，FQs resistance rates were notably high at 33.12%（158/477）and 36.84%（140/380），respectively. Conclusions:The MTB resistance situation in the hospital has gradually declined in the past 10 years，but the resistance situation remains severe，and clinical attention needs to be strengthened on the use of FQs.

Objective:To analyze the drug resistance status of Mycobacterium tuberculosis（MTB）at a hospital in Xiamen over the past decade. Methods:Sputum culture-positive specimens of tuberculosis patients from Xiamen Xinglin Hospital from 2015 to 2024 were collected retrospectively. Isolates were identified as MTB complex and subjected to drug susceptibility testing. Drug resistance patterns and trends over the study period were analyzed using descriptive statistics and Chi-square trend tests in SPSS 27.0 and GraphPad Prism 8.0.Results:Among 3 883 MTB isolates analyzed，1 132（29.15%）exhibited resistance to at least one drug. The highest rates of resistance to individual first-line drugs were observed for isoniazid（INH，16.04%），streptomycin（SM，15.43%），and rifampicin（RFP，12.28%）. Multidrug-resistant tuberculosis（MDR-TB）was identified in 380 isolates（9.79%）. The predominant MDR resistance patterns were INH+RFP+SM（2.34%），INH+RFP（1.65%），and INH+RFP+SM+ethambutol（EMB）（1.03%）. Polyresistance was found in 188 isolates（4.84%），the predominant patterns were INH+SM（1.49%），INH+fluoroquinolone（FQs）（0.31%），and INH+para-aminosalicylic acid（PAS）（0.31%）. Extensively drug-resistant tuberculosis（XDR-TB）was detected in 49 isolates（1.26%）. From 2015 to 2024，significant decreasing trends were observed for overall drug resistance（ χ2=8.858， P=0.003），MDR（ χ2=15.692， P<0.001），and RFP resistance（ χ2=21.627， P<0.001）. In contrast，fluoroquinolone（FQs）resistance showed no significant trend（ χ2=0.149， P=0.699）. Among RFP resistant and MDR isolates，FQs resistance rates were notably high at 33.12%（158/477）and 36.84%（140/380），respectively. Conclusions:The MTB resistance situation in the hospital has gradually declined in the past 10 years，but the resistance situation remains severe，and clinical attention needs to be strengthened on the use of FQs.

Objective To investigate the relationship between the therapeutic effect of anti-vascular endothelial growth factor(VEGF)and cytokines in aqueous humor in patients with diabetic retinopathy(DR).Methods From July 2023 to December 2023,50 DR patients(56 eyes)who were treated with anti-VEGF drugs in the Department of Ophthal-mology,the Third Affiliated Hospital of Xinxiang Medical University were included in this study.The patients were divided into the diabetic macular edema(DME)group(30 patients,36 eyes)and the proliferative DR(PDR)group(20 patients,20 eyes).Patients in the DME group received an intravitreal injection of aflibercept once a month for three consecutive times,with aqueous humor extracted before each injection.Patients in the PDR group received an intravitreal injection of aflibercept one week before vitrectomy,with aqueous humor extracted before injection and during vitrectomy,respective-ly.The concentrations of vascular endothelial growth factor A(VEGF-A),placental growth factor(PLGF),interleukin(IL)-1β,IL-23,IL-17A,and tumor necrosis factor-α(TNF-α)in the aqueous humor were detected using the Luminex as-say.Before injection therapy,all patients underwent best corrected visual acuity(BCVA)and central macular thickness(CMT)examinations,and their correlations with cytokine concentrations in DR patients before injection therapy were ana-lyzed.Results Compared to before injection therapy,the concentrations of VEGF-A,PLGF,and IL-23 in the aqueous humor of patients in the DME group decreased significantly after treatment(all P＜0.05);additionally,the CMT de-creased,and the BCVA increased(both P＜0.05).After injection therapy,the concentrations of VEGF,PLGF,IL-1β,IL-23,IL-17A,and TNF-α in the aqueous humor of patients in the PDR group significantly decreased compared to before injec-tion therapy(all P＜0.05).Before injection therapy,the levels of VEGF-A,PLGF,and IL-23 in the aqueous humor of pa-tients in the DME group were higher than those in the PDR group,and the differences were statistically significant(all P＜0.05).The correlation analysis results showed that before injection therapy,VEGF was negatively correlated with BCVA(r=-0.767,P=0.004)and was positively correlated with CMT(r=0.662,P=0.019)and IL-23(r=0.765,P=0.004)in the DME group.There was no correlation between the cytokines in the aqueous humor of patients in the PDR group be-fore injection therapy(all P＞0.05).Conclusion Changes in the concentration of VEGF-A,PLGF,and IL-23 are closely related to the occurrence and development of DR.Anti-VEGF treatment can improve BCVA and decrease CMT in DME pa-tients.The expression level of IL-23 in aqueous humor can serve as a predictive factor for the anti-VEGF efficacy in DR pa-tients,providing new targets for early diagnosis and treatment of DR.

Objective To analyze and compare the changes in local functional activity of the brain under different recovery times after a 90-day,-6° head down bed rest(HDBR)experiment,clarify the mechanism of brain function remodeling during gravity adaptation,and provide imaging basis and guidance for the model construction and health assessment.Methods 36 healthy male volunteers underwent resting-state functional magnetic resonance imaging(rs-fMRI)scans before HDBR(PRE),3 days after 90-day HDBR(R+3),and 26-28 days after 90-day HDBR(R+26-28),and calculated regional homogeneity(ReHo)and low-frequency amplitude(ALFF)and perform statistical analysis between different time points.Results Compared with PRE-status,ReHo value in the left inferior parietal gyrus and ALFF value in the right posterior cingulate gyrus decreased significantly in R+3 status,while ReHo value in the left calcarine,right lingual gyrus and ALFF value in the precuneus,left paracentral lobule,and right postcentral gyrus increased significantly.At R+26-28 status,more brain areas showed significant changes.Conclusion 90 days of long-term HDBR and subsequent recovery will lead to changes in the neural functional activities of the brain's default network,sensorimotor network and visual network,and obvious adaptive remodeling will occur after a longer period of gravity re-adaptation and recovery.

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 study the effects of vision on human postural control and the connection mechanisms of the brain's functional network.Methods 15 healthy male adults were required to perform 30 s of balanced standing on both legs with eyes open and eyes closed.The center of pressure(COP)and electroencephalograph(EEG)were recorded during balance.The sample entropy(sample En)of the COP was calculated.The phase lag index(PLI)in θ-,α-,β-band of EEG was calculated to construct the brain functional networks,and the clustering coefficient(C),characteristic path length(L),and the criteria(σ)of the small-world network were calculated based on graph theory.Results During balanced standing on both legs,the SampleEn of the COPY with eyes closed was significantly higher than that with eyes open(P＜0.05).The mean value of PLI in the α-band under the eyes closed state was significantly higher than that under the eyes open state(P＜0.05).The C and σ values in the α-band under the eyes closed state were significantly higher than those under the eyes open state,and the L value was significantly lower than that under the eyes open state(P＜0.05).The frontal-central-parietal connectivity and the central-parietal connectivity strength in the α-band under the eyes closed state were significantly higher than those under the eyes open state(P＜0.05).The average PLI and C values in the α-band were moderately negatively correlated with the SampleEn of COPY (P＜0.05).The average PLI of the left prefrontal area,left parietal area,and left occipital area in the α-band under the eyes closed state had a moderate negative correlation with the SampleEn of COPY.The average PLI of the left central region and the right occipital area in the eyes-closed state was moderately negatively correlated with the SampleEn of COPY.Conclusions During the standing balance,when there is no visual input,the stability of body balance decreases,accompanied by enhanced brain network connectivity in α-band and the requirement for efficiency enhancement in information processing in the brain.The brain adopts different neural strategies when performing postural control under various visual conditions.

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 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 evaluate the efficacy and safety of intravitreal ranibizumab combined with laser (IVR+ Laser) and the intravitreal ranibizumab (IVR) monotherapy for the treatment of diabetic macular edema (DME).Methods:A meta-analysis was conducted on randomized controlled trial (RCT) literature related to IVR+ Laser therapy and IVR alone for DME.Databases including Cochrane Library, PubMed, EMbase, Web of Science, SinoMed, CNKI, VIP and WanFang Data were searched from their inception to April 2022.Literature screening, data extraction, quality evaluation and cross-checking were conducted independently by two researchers according to inclusion and exclusion criteria.Then a meta-analysis was conducted using RevMan 5.4.1 software.The two therapies were compared in terms of best corrected visual acuity (BCVA), central macular thickness (CMT), mean number of injections and adverse events.Results:Twelve RCTs involving 1 695 eyes were included in the study.Meta-analysis showed that at the end of follow-up, IVR+ Laser demonstrated better improvement in BCVA and CMT than IVR alone, and there were significant differences in the changes in BCVA and CMT between the two groups (weighted mean difference[WMD]=-0.66, 95% confidence interval[ CI]: -1.11--0.21, P<0.01; WMD=-5.05, 95% CI: -9.21--0.89, P=0.02).IVR+ Laser required significantly fewer injections than IVR alone (WMD=-1.16, 95% CI: -2.07--0.25, P=0.01).There were no significant differences in the adverse events incidence between the two therapies (all at P>0.05). Conclusions:The safety of IVR+ Laser is comparable to IVR alone, and it requires fewer injections for the treatment of DME.

Approximately 140 million people worldwide are homozygous carriers of APOE4 (ε4), a strong genetic risk factor for late onset familial and sporadic Alzheimer's disease (AD), 91% of whom will develop AD at earlier age than heterozygous carriers and noncarriers. Susceptibility to AD could be reduced by targeted editing of APOE4, but a technical basis for controlling the off-target effects of base editors is necessary to develop low-risk personalized gene therapies. Here, we first screened eight cytosine base editor variants at four injection stages (from 1- to 8-cell stage), and found that FNLS-YE1 variant in 8-cell embryos achieved the comparable base conversion rate (up to 100%) with the lowest bystander effects. In particular, 80% of AD-susceptible ε4 allele copies were converted to the AD-neutral ε3 allele in human ε4-carrying embryos. Stringent control measures combined with targeted deep sequencing, whole genome sequencing, and RNA sequencing showed no DNA or RNA off-target events in FNLS-YE1-treated human embryos or their derived stem cells. Furthermore, base editing with FNLS-YE1 showed no effects on embryo development to the blastocyst stage. Finally, we also demonstrated FNLS-YE1 could introduce known protective variants in human embryos to potentially reduce human susceptivity to systemic lupus erythematosus and familial hypercholesterolemia. Our study therefore suggests that base editing with FNLS-YE1 can efficiently and safely introduce known preventive variants in 8-cell human embryos, a potential approach for reducing human susceptibility to AD or other genetic diseases.
Humans ; Apolipoprotein E4/genetics* ; Cytosine ; Mutation ; Blastocyst ; Heterozygote ; Gene Editing ; CRISPR-Cas Systems