AIM:To explore the impact of chronic stress on postoperative cognitive dysfunction in rats and to elucidate the mechanistic link to histone deacetylase 2(HDAC2).METHODS:A repeated social defeat stress model and a prolonged isoflurane anesthesia model were established in mice.The rats were randomly assigned to four groups:control(Ctrl)group,isoflurane anesthesia(Iso)group,chronic social defeat stress(RSDS)group,and chronic social de-feat stress combined with isoflurane anesthesia(RSDS+Iso)group.Anxiety-like behaviors were evaluated using the social avoidance test and the novelty-suppressed feeding test.Cognitive function was assessed through the novel object recogni-tion test and the Morris water maze.Plasma corticosterone levels were measured via enzyme-linked immunosorbent assay(ELISA).Primary hippocampal neurons were isolated from fetal mouse hippocampi and classified into four groups:con-trol group,chronic stress combined with prolonged isoflurane anesthesia(Cort+Iso)group,CAY-10683 intervention(CAY),and CAY-10683 treatment(CAY+Cort+Iso)group.Cell viability was determined using CCK-8 assay,and pro-tein expression levels of brain-derived neurotrophic factor(BDNF)and HDAC2 were analyzed by Western blot.RE-SULTS:The RSDS mouse model was successfully established,with ELISA results indicating a significant increase in plasma corticosterone levels in mice subjected to chronic stress combined with prolonged isoflurane anesthesia.Behavioral assessments and Western blot analyses revealed that mice exposed to prolonged isoflurane anesthesia following chronic stress showed marked declines in cognitive function and hippocampal BDNF protein expression levels.Additionally,chronic stress significantly elevated HDAC2 protein expression in the hippocampi of mice undergoing prolonged isoflurane anesthesia.Treatment with an HDAC2 inhibitor reduced HDAC2 protein expression in primary hippocampal neurons sub-jected to chronic stress combined with prolonged isoflurane anesthesia,concurrently increasing BDNF protein expression levels.CONCLUSION:Chronic stress significantly worsens postoperative cognitive dysfunction induced by prolonged isoflurane anesthesia,associated with increased HDAC2 protein expression in the hippocampus.Inhibition of HDAC2 ef-fectively counteracts the reduction in BDNF,a protein crucial for cognitive function,caused by the combination of chronic stress and prolonged isoflurane anesthesia.

Purpose To investigate the distribution characteristics of tumor-associated macrophages(TAM)in different regions of breast cancer with enhanced contrast-enhanced ultrasound(CEUS),and to further explore the relationship between TAM and CEUS indicators and clinicopathology in different regions of breast cancer.Materials and Methods A total of 119 patients with suspected breast cancer admitted to the Cancer Hospital Affiliated to Xinjiang Medical University from March 2021 to March 2023 were prospectively included.CEUS was applied to the tumor,and ultrasound-guided puncture biopsy was also taken.The lesions diagnosed as breast cancer by pathology was outlined the central area,marginal area and normal area next to the cancer,and was obtained the time intensity curves of different areas.The tissues were taken for immunohistochemistry and flow cytometry,and the TAM cells were stained and distinguished.The characteristics of TAM in different regions of breast cancer and its correlation with clinical pathology were analyzed,respectively.Results By immunohistochemistry and flow cytometry,there were significant differences in the number of TAM infiltration in the border area,central area and adjacent area of breast cancer(immunohistochemistry:F=382.326,P<0.05;flow cytometry:F=24.955,P<0.05).The characteristics of CEUS in three different regions showed that the TAM in the central region of breast cancer increased when filling defect appeared(t=2.631,P<0.05),but the TAM in the peripheral region was more(t=2.999,P<0.05).After angiography,lesions showed high perfusion,and there was significantly more TAM in the edge and central area of the lesion than that in normal area next to the cancer(t=5.529,P<0.05;t=2.584,P<0.05).Clinical stage was related to the TAM in three regions.When the clinical stage was high,there were more TAM in all three regions(t=6.658,2.367,2.400,all P<0.05).Histological grading was high,and TAM in all three areas was high(F=101.151,16.922,26.822,all P<0.05).Conclusion There was a decreasing trend of TAM in the marginal area,central area and adjacent tissues of breast cancer during CEUS.The edge region has more malignant CEUS characteristics than that in the central region and the normal region adjacent to cancer;and the number of TAM is more in breast cancer with late clinical grading,poor tissue differentiation and obvious contrast-enhanced ultrasound malignant characteristics.The distribution characteristics of TAM represent the malignant degree and metastatic probability of breast cancer to a certain extent,and TAM is a factor related to the invasion of breast cancer.

Objective:To report the nationwide surveillance results of pathogenic profiles and antimicrobial resistance patterns of Gram-positive bloodstream infections in China in 2023.Methods:The clinical isolates of Gram-posttive bacteria from blood cultures were collected in member hospitals of National Bloodstream Infection Bacterial Resistant Investigation Collaborative System（BRICS）during January to December 2023. Antimicrobial susceptibility testing was performed using the dilution method recommended by the Clinical and Laboratory Standards Institute（CLSI）. Statistical analyses were conducted using WHONET 5.6 and SPSS 25.0 software.Results:A total of 4 385 Gram-positive bacterial isolates were obtained from 60 participating center. The top five pathogens were Staphylococcus aureus（ n=1 544，35.2%），coagulase-negative Staphylococci（ n=1 441，32.9%）， Enterococcus faecium（ n=574，13.1%）， Enterococcus faecalis（ n=385，8.8%），and α-hemolytic Streptococci（ n=187，4.3%）. The prevalence of methicillin-resistant Staphylococcus aureus（MRSA）and methicillin-resistant coagulase-negative Staphylococci（MRCNS）was 26.2%（405/1 544）and 69.8%（1 006/1 441），respectively. Notably，all Staphylococci remained susceptible to glycopeptide or daptomycin. Staphylococcus aureus demonstrated excellent susceptibility（>97.0%）to cephalobiol，rifampicin，trimethoprim-sulfamethoxazole，linezolid，minocycline，tigecycline，and eravacycline. No Enterococcus exhibiting resistance to linezolid were detected. Glycopeptide resistance was uncommon but more frequent in Enterococcus faecium（resistance to vancomycin and teicoplanin：both 1.7%）compared to Enterococcus faecalis（both 0.3%）. The detection rates of MRSA and MRCNS exhibited significant regional variations across the country（ χ2=17.674 and 148.650，respectively，both P<0.001）. No vancomycin-resistant Enterococci were detected in central China. Institutional comparison demonstrated higher prevalence of MRSA（ χ2=14.111， P<0.001）and MRCNS（ χ2=4.828， P=0.028）in provincial hospitals than that in municipal hospitals. Socioeconomic analysis identified elevated detection rates of both MRSA（ χ2=18.986， P<0.001）and MRCNS（ χ2=4.477， P=0.034）in less developed regions（per capita GDP

Objective:To report the results of bacterial resistant investigation collaborative system（BRICS）on the distribution and antimicrobial resistance profile of clinical Gram-negative bacteria isolates from bloodstream infections in China in 2023，and provide reference for clinical tretment of bloodstream infections and prevention and control of bacterial resistance.Methods:The clinical isolates of Gram-negative bacteria from blood cultures in member hospitals of BRICS were collected during January 2023 to December 2023. Antibiotic susceptibility tests were conducted by agar dilution or broth dilution methods recommended by Clinical and Laboratory Standards Institute（CLSI）. WHONET 5.6 and SPSS 25.0 were used to analyze the data.Results:During the study period，11 492 strains of Gram-negative bacteria were collected from 60 hospitals，of which 10 098（87.9%）were Enterobacterales and 1 394（12.1%）were non-fermentative bacteria. The top 5 bacterial species were Escherichia coli（50.0%）， Klebsiella pneumoniae（26.1%）， Pseudomonas aeruginosa（5.1%）， Acinetobacter baumannii complex（5.0%）and Enterobacter cloacae complex（4.1%）. The ESBL-producing rates in Escherichia coli， Klebsiella pneumoniae and Proteus mirablilis were 46.8%（2 685/5 741），18.3%（549/2 999）and 44.0%（77/175），respectively. The prevalence of carbapenem-resistant Escherichia coli（CREC）and carbapenem-resistant Klebsiella pneumoniae（CRKP）were 1.3%（76/5 741）and 15.0%（450/2 999）；32.9%（25/76）and 78.0%（351/450）of CREC and CRKP were sensitive to ceftazidime/avibactam combination，respectively. 94.7%（72/76）and 90.2%（406/450）of CREC and CRKP were sensitive to aztreonam/avibactam combination. Furthermore，57.9%（44/76）and 79.1%（356/450）were sensitive to imipenem/relebactam combination. The prevalence of carbapenem-resistant Acinetobacter baumannii（CRAB）complex was 64.6%（370/573），while more than 80.0% of CRAB complex was sensitive to tigecycline，eravacycline and polymyxin B. The prevalence of carbapenem-resistant Pseudomonas aeruginosa（CRPA）was 17.0%（99/581）. There were differences in the composition ratio of Gram-negative bacteria in bloodstream infections and the prevalence of important Gram-negative bacteria resistance among different regions in China，with statistically significant differences in the prevalence of CREC，CRKP，CRPA and CRAB complex（ χ2=10.6，28.6，10.8 and 19.3， P<0.05）. The prevalence of ESBL-producing Escherichia coli， CREC，CRAB complex and CRKP were higher in provincial hospitals than those in municipal hospitals（ χ2=12.5，9.8，12.7 and 57.8，all P<0.01）. Conclusions:Gram-negative bacteria are the main pathogens causing bloodstream infections in China，and Escherichia coli is ranked in the top，while the trend of Klebsiella pneumoniae increases continuously with time. CRKP infection shows a slow upward trend，CREC infecton maintains a low prevalence level，and CRAB complex infection continues to exhibit a high prevalence rate. The composition and resistance patterns of pathogens causing bloodstream infections vary to some extent across different regions and levels of hospitals in China.

Purpose To investigate the distribution characteristics of tumor-associated macrophages(TAM)in different regions of breast cancer with enhanced contrast-enhanced ultrasound(CEUS),and to further explore the relationship between TAM and CEUS indicators and clinicopathology in different regions of breast cancer.Materials and Methods A total of 119 patients with suspected breast cancer admitted to the Cancer Hospital Affiliated to Xinjiang Medical University from March 2021 to March 2023 were prospectively included.CEUS was applied to the tumor,and ultrasound-guided puncture biopsy was also taken.The lesions diagnosed as breast cancer by pathology was outlined the central area,marginal area and normal area next to the cancer,and was obtained the time intensity curves of different areas.The tissues were taken for immunohistochemistry and flow cytometry,and the TAM cells were stained and distinguished.The characteristics of TAM in different regions of breast cancer and its correlation with clinical pathology were analyzed,respectively.Results By immunohistochemistry and flow cytometry,there were significant differences in the number of TAM infiltration in the border area,central area and adjacent area of breast cancer(immunohistochemistry:F=382.326,P<0.05;flow cytometry:F=24.955,P<0.05).The characteristics of CEUS in three different regions showed that the TAM in the central region of breast cancer increased when filling defect appeared(t=2.631,P<0.05),but the TAM in the peripheral region was more(t=2.999,P<0.05).After angiography,lesions showed high perfusion,and there was significantly more TAM in the edge and central area of the lesion than that in normal area next to the cancer(t=5.529,P<0.05;t=2.584,P<0.05).Clinical stage was related to the TAM in three regions.When the clinical stage was high,there were more TAM in all three regions(t=6.658,2.367,2.400,all P<0.05).Histological grading was high,and TAM in all three areas was high(F=101.151,16.922,26.822,all P<0.05).Conclusion There was a decreasing trend of TAM in the marginal area,central area and adjacent tissues of breast cancer during CEUS.The edge region has more malignant CEUS characteristics than that in the central region and the normal region adjacent to cancer;and the number of TAM is more in breast cancer with late clinical grading,poor tissue differentiation and obvious contrast-enhanced ultrasound malignant characteristics.The distribution characteristics of TAM represent the malignant degree and metastatic probability of breast cancer to a certain extent,and TAM is a factor related to the invasion of breast cancer.

AIM:To explore the impact of chronic stress on postoperative cognitive dysfunction in rats and to elucidate the mechanistic link to histone deacetylase 2(HDAC2).METHODS:A repeated social defeat stress model and a prolonged isoflurane anesthesia model were established in mice.The rats were randomly assigned to four groups:control(Ctrl)group,isoflurane anesthesia(Iso)group,chronic social defeat stress(RSDS)group,and chronic social de-feat stress combined with isoflurane anesthesia(RSDS+Iso)group.Anxiety-like behaviors were evaluated using the social avoidance test and the novelty-suppressed feeding test.Cognitive function was assessed through the novel object recogni-tion test and the Morris water maze.Plasma corticosterone levels were measured via enzyme-linked immunosorbent assay(ELISA).Primary hippocampal neurons were isolated from fetal mouse hippocampi and classified into four groups:con-trol group,chronic stress combined with prolonged isoflurane anesthesia(Cort+Iso)group,CAY-10683 intervention(CAY),and CAY-10683 treatment(CAY+Cort+Iso)group.Cell viability was determined using CCK-8 assay,and pro-tein expression levels of brain-derived neurotrophic factor(BDNF)and HDAC2 were analyzed by Western blot.RE-SULTS:The RSDS mouse model was successfully established,with ELISA results indicating a significant increase in plasma corticosterone levels in mice subjected to chronic stress combined with prolonged isoflurane anesthesia.Behavioral assessments and Western blot analyses revealed that mice exposed to prolonged isoflurane anesthesia following chronic stress showed marked declines in cognitive function and hippocampal BDNF protein expression levels.Additionally,chronic stress significantly elevated HDAC2 protein expression in the hippocampi of mice undergoing prolonged isoflurane anesthesia.Treatment with an HDAC2 inhibitor reduced HDAC2 protein expression in primary hippocampal neurons sub-jected to chronic stress combined with prolonged isoflurane anesthesia,concurrently increasing BDNF protein expression levels.CONCLUSION:Chronic stress significantly worsens postoperative cognitive dysfunction induced by prolonged isoflurane anesthesia,associated with increased HDAC2 protein expression in the hippocampus.Inhibition of HDAC2 ef-fectively counteracts the reduction in BDNF,a protein crucial for cognitive function,caused by the combination of chronic stress and prolonged isoflurane anesthesia.

Objective:To report the nationwide surveillance results of pathogenic profiles and antimicrobial resistance patterns of Gram-positive bloodstream infections in China in 2023.Methods:The clinical isolates of Gram-posttive bacteria from blood cultures were collected in member hospitals of National Bloodstream Infection Bacterial Resistant Investigation Collaborative System（BRICS）during January to December 2023. Antimicrobial susceptibility testing was performed using the dilution method recommended by the Clinical and Laboratory Standards Institute（CLSI）. Statistical analyses were conducted using WHONET 5.6 and SPSS 25.0 software.Results:A total of 4 385 Gram-positive bacterial isolates were obtained from 60 participating center. The top five pathogens were Staphylococcus aureus（ n=1 544，35.2%），coagulase-negative Staphylococci（ n=1 441，32.9%）， Enterococcus faecium（ n=574，13.1%）， Enterococcus faecalis（ n=385，8.8%），and α-hemolytic Streptococci（ n=187，4.3%）. The prevalence of methicillin-resistant Staphylococcus aureus（MRSA）and methicillin-resistant coagulase-negative Staphylococci（MRCNS）was 26.2%（405/1 544）and 69.8%（1 006/1 441），respectively. Notably，all Staphylococci remained susceptible to glycopeptide or daptomycin. Staphylococcus aureus demonstrated excellent susceptibility（>97.0%）to cephalobiol，rifampicin，trimethoprim-sulfamethoxazole，linezolid，minocycline，tigecycline，and eravacycline. No Enterococcus exhibiting resistance to linezolid were detected. Glycopeptide resistance was uncommon but more frequent in Enterococcus faecium（resistance to vancomycin and teicoplanin：both 1.7%）compared to Enterococcus faecalis（both 0.3%）. The detection rates of MRSA and MRCNS exhibited significant regional variations across the country（ χ2=17.674 and 148.650，respectively，both P<0.001）. No vancomycin-resistant Enterococci were detected in central China. Institutional comparison demonstrated higher prevalence of MRSA（ χ2=14.111， P<0.001）and MRCNS（ χ2=4.828， P=0.028）in provincial hospitals than that in municipal hospitals. Socioeconomic analysis identified elevated detection rates of both MRSA（ χ2=18.986， P<0.001）and MRCNS（ χ2=4.477， P=0.034）in less developed regions（per capita GDP

Objective:To report the results of bacterial resistant investigation collaborative system（BRICS）on the distribution and antimicrobial resistance profile of clinical Gram-negative bacteria isolates from bloodstream infections in China in 2023，and provide reference for clinical tretment of bloodstream infections and prevention and control of bacterial resistance.Methods:The clinical isolates of Gram-negative bacteria from blood cultures in member hospitals of BRICS were collected during January 2023 to December 2023. Antibiotic susceptibility tests were conducted by agar dilution or broth dilution methods recommended by Clinical and Laboratory Standards Institute（CLSI）. WHONET 5.6 and SPSS 25.0 were used to analyze the data.Results:During the study period，11 492 strains of Gram-negative bacteria were collected from 60 hospitals，of which 10 098（87.9%）were Enterobacterales and 1 394（12.1%）were non-fermentative bacteria. The top 5 bacterial species were Escherichia coli（50.0%）， Klebsiella pneumoniae（26.1%）， Pseudomonas aeruginosa（5.1%）， Acinetobacter baumannii complex（5.0%）and Enterobacter cloacae complex（4.1%）. The ESBL-producing rates in Escherichia coli， Klebsiella pneumoniae and Proteus mirablilis were 46.8%（2 685/5 741），18.3%（549/2 999）and 44.0%（77/175），respectively. The prevalence of carbapenem-resistant Escherichia coli（CREC）and carbapenem-resistant Klebsiella pneumoniae（CRKP）were 1.3%（76/5 741）and 15.0%（450/2 999）；32.9%（25/76）and 78.0%（351/450）of CREC and CRKP were sensitive to ceftazidime/avibactam combination，respectively. 94.7%（72/76）and 90.2%（406/450）of CREC and CRKP were sensitive to aztreonam/avibactam combination. Furthermore，57.9%（44/76）and 79.1%（356/450）were sensitive to imipenem/relebactam combination. The prevalence of carbapenem-resistant Acinetobacter baumannii（CRAB）complex was 64.6%（370/573），while more than 80.0% of CRAB complex was sensitive to tigecycline，eravacycline and polymyxin B. The prevalence of carbapenem-resistant Pseudomonas aeruginosa（CRPA）was 17.0%（99/581）. There were differences in the composition ratio of Gram-negative bacteria in bloodstream infections and the prevalence of important Gram-negative bacteria resistance among different regions in China，with statistically significant differences in the prevalence of CREC，CRKP，CRPA and CRAB complex（ χ2=10.6，28.6，10.8 and 19.3， P<0.05）. The prevalence of ESBL-producing Escherichia coli， CREC，CRAB complex and CRKP were higher in provincial hospitals than those in municipal hospitals（ χ2=12.5，9.8，12.7 and 57.8，all P<0.01）. Conclusions:Gram-negative bacteria are the main pathogens causing bloodstream infections in China，and Escherichia coli is ranked in the top，while the trend of Klebsiella pneumoniae increases continuously with time. CRKP infection shows a slow upward trend，CREC infecton maintains a low prevalence level，and CRAB complex infection continues to exhibit a high prevalence rate. The composition and resistance patterns of pathogens causing bloodstream infections vary to some extent across different regions and levels of hospitals in China.

Objective:To report the results of national surveillance on the distribution and antimicrobial resistance profile of clinical Gram-negative bacteria isolates from bloodstream infections in China in 2022.Methods:The clinical isolates of Gram-negative bacteria from blood cultures in member hospitals of national bloodstream infection Bacterial Resistant Investigation Collaborative System（BRICS）were collected during January 2022 to December 2022. Antibiotic susceptibility tests were conducted by agar dilution or broth dilution methods recommended by Clinical and Laboratory Standards Institute（CLSI）. WHONET 5.6 and SPSS 25.0 software were used to analyze the data.Results:During the study period，9 035 strains of Gram-negative bacteria were collected from 51 hospitals，of which 7 895（87.4%）were Enterobacteriaceae and 1 140（12.6%）were non-fermenting bacteria. The top 5 bacterial species were Escherichia coli（ n=4 510，49.9%）， Klebsiella pneumoniae（ n=2 340，25.9%）， Pseudomonas aeruginosa（ n=534，5.9%）， Acinetobacter baumannii complex（ n=405，4.5%）and Enterobacter cloacae（ n=327，3.6%）. The ESBLs-producing rates in Escherichia coli， Klebsiella pneumoniae and Proteus spp. were 47.1%（2 095/4 452），21.0%（427/2 033）and 41.1%（58/141），respectively. The prevalence of carbapenem-resistant Escherichia coli（CREC）and carbapenem-resistant Klebsiella pneumoniae（CRKP）were 1.3%（58/4 510）and 13.1%（307/2 340）；62.1%（36/58）and 9.8%（30/307）of CREC and CRKP were resistant to ceftazidime/avibactam combination，respectively. The prevalence of carbapenem-resistant Acinetobacter baumannii（CRAB）complex was 59.5%（241/405），while less than 5% of Acinetobacter baumannii complex was resistant to tigecycline and polymyxin B. The prevalence of carbapenem-resistant Pseudomonas aeruginosa（CRPA）was 18.4%（98/534）. There were differences in the composition ratio of Gram-negative bacteria in bloodstream infections and the prevalence of main Gram-negative bacteria resistance among different regions，with statistically significant differences in the prevalence of CRKP and CRPA（ χ2=20.489 and 20.252， P<0.001）. The prevalence of CREC，CRKP，CRPA，CRAB，ESBLs-producing Escherichia coli and Klebsiella pneumoniae were higher in provinicial hospitals than those in municipal hospitals（ χ2=11.953，81.183，10.404，5.915，12.415 and 6.459， P<0.01 or <0.05），while the prevalence of CRPA was higher in economically developed regions（per capita GDP ≥ 92 059 Yuan）than that in economically less-developed regions（per capita GDP <92 059 Yuan）（ χ2=6.240， P=0.012）. Conclusions:The proportion of Gram-negative bacteria in bloodstream infections shows an increasing trend，and Escherichia coli is ranked in the top，while the trend of CRKP decreases continuously with time. Decreasing trends are noted in ESBLs-producing Escherichia coli and Klebsiella pneumoniae. Low prevalence of carbapenem resistance in Escherichia coli and high prevalence in CRAB complex have been observed. The composition ratio and antibacterial spectrum of bloodstream infections in different regions of China are slightly different，and the proportion of main drug resistant bacteria in provincial hospitals is higher than those in municipal hospitals.

Background::Total human immunodeficiency virus (HIV) DNA and integrated HIV DNA are widely used markers of HIV persistence. Droplet digital polymerase chain reaction (ddPCR) can be used for absolute quantification without needing a standard curve. Here, we developed duplex ddPCR assays to detect and quantify total HIV DNA and integrated HIV DNA.Methods::The limit of detection, dynamic ranges, sensitivity, and reproducibility were evaluated by plasmid constructs containing both the HIV long terminal repeat (LTR) and human CD3 gene (for total HIV DNA) and ACH-2 cells (for integrated HIV DNA). Forty-two cases on stable suppressive antiretroviral therapy (ART) were assayed in total HIV DNA and integrated HIV DNA. Correlation coefficient analysis was performed on the data related to DNA copies and cluster of differentiation 4 positive (CD4 +) T-cell counts, CD8 + T-cell counts and CD4/CD8 T-cell ratio, respectively. The assay linear dynamic range and lower limit of detection (LLOD) were also assessed. Results::The assay could detect the presence of HIV-1 copies 100% at concentrations of 6.3 copies/reaction, and the estimated LLOD of the ddPCR assay was 4.4 HIV DNA copies/reaction (95% confidence intervals [CI]: 3.6-6.5 copies/reaction) with linearity over a 5-log 10-unit range in total HIV DNA assay. For the integrated HIV DNA assay, the LLOD was 8.0 copies/reaction (95% CI: 5.8-16.6 copies/reaction) with linearity over a 3-log 10-unit range. Total HIV DNA in CD4 + T cells was positively associated with integrated HIV DNA ( r = 0.76, P <0.0001). Meanwhile, both total HIV DNA and integrated HIV DNA in CD4 + T cells were inversely correlated with the ratio of CD4/CD8 but positively correlated with the CD8 + T-cell counts. Conclusions::This ddPCR assay can quantify total HIV DNA and integrated HIV DNA efficiently with robustness and sensitivity. It can be readily adapted for measuring HIV DNA with non-B clades, and it could be beneficial for testing in clinical trials.