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 investigate the effect of type 2 taste receptor(T2R)38 activation on ferroptosis of human airway epithelium NuLi-1 cells induced by cigarette smoke exposure,and to clarify its possible mechanism.Methods:The human airway epithelial NuLi-1 cells were divided into control group(without any treatment),cigarette smoke extract(CSE)group(treated with 5％CSE for 24 h)and CSE+T2R38 specific agonist phenylthiocarbamide(PTC)group(CSE+PTC group)(treated with 5％CSE and 1 mmol·L-1 PTC for 24 h).The expression levels of T2R38 mRNA and protein in NuLi-1 cells in various groups were determined by real-time fluorescence quantitative PCR(RT-qPCR)and Western blotting methods.The cell viabilities in various groups were determined by cell counting kit-8(CCK-8)assay.The activities of inducible nitric oxide synthase(iNOS),endothelial nitric oxide synthase(eNOS),and superoxide dismutase(SOD)in the cells in various groups were measured by kits.DAX-J2 red fluorescence probe was used to determine the levels of nitric oxide(NO)in the cells in various groups.The reactive oxygen species(ROS)levels in the cells in various groups were detected by fluorescent probe kit.The levels of malondialdehyde(MDA),Fe2+,and reduced glutathione(GSH)in the cells in various groups were determined by enzyme-linked immunosorbent assay(ELISA)method.Western blotting method was used to determine the expression levels of nuclear factor erythroid 2-related factor 2(Nrf2)and glutathione peroxidases 4(GPx4)proteins in the cells in various groups.Results:Compared with control group,the expression levels of T2R38 mRNA and protein in NuLi-1 cells in CSE group were increased(P＜0.05).Compared with control group,the viability of NuLi-1 cells in CSE group was decreased(P＜0.05),the activities of iNOS and SOD in cells in CSE group were increased(P＜0.05),the levels of NO and ROS were increased(P＜0.05),the levels of MDA and Fe2+were increased(P＜0.05),and the GSH level and the expression levels of Nrf2 and GPx4 proteins were decreased.Compared with CSE group,the viability of NuLi-1 cells in CSE+PTC group was increased(P＜0.05),the activity of SOD and the GSH level in the cells were increased(P＜0.05),the activity of iNOS in cells was decreased(P＜0.05),the levels of NO and ROS in cells were decreased(P＜0.05),the levels of MDA and Fe2+were decreased(P＜0.05),and the expression levels of Nrf2 and GPx4 proteins were increased(P＜0.05).There was no significant difference in eNOS activity among control group,CSE group,and CSE+PTC group(P＞0.05).Conclusion:Activation of bitter taste receptor T2R38 can inhibit ferroptosis in human airway epithelium NuLi-1 cells induced by cigarette smoke exposure,and its mechanism may be related to the reduction of iNOS activity in the cells.

Abnormal amino acid metabolism promotes tumor progression by inducing malignant behaviors in tumor cells and altering the immune landscape within the tumor microenvironment. However, the underlying mechanisms remain unclear. In this study, we constructed colorectal cancer (CRC) organoids and patient-derived tumor xenograft (PDX) models, performing multifaceted validation to confirm that T-complex protein 1 subunit epsilon (CCT5), mediates the biosynthesis of aspartate and enhances sensitivity to anti-PD-L1 immunotherapy. Mechanistically, CCT5 directly binds to asparagine synthetase (ASNS) and promotes the synthesis of aspartate (Asn). The Asn-mTORC1 axis facilitates tumor cell proliferation while upregulating PD-L1 expression, which leads to a reduction in the number of effector CD8⁺ T cells. Treatment with l-asparaginase (ASNase) combined with anti-PD-L1 therapy effectively reverses the growth of CRC characterized by high CCT5 expression. In summary, we identify CCT5 as a potential biomarker to guide the combined use of ASNase and anti-PD-L1 antibodies in CRC treatment.

Objective:To access the relation of aortic arch calcification (AoAC) volume based on parathyroid SPECT/CT imaging with hungry bone syndrome (HBS) in patients with renal secondary hyperparathyroidism (SHPT) after parathyroidectomy (PTX).Methods:From June 2015 to May 2024, the imaging and clinical data of 89 renal SHPT patients (52 males, 37 females, age: (51.5±10.3) years) who underwent parathyroid 99Tc m-methoxyisobutylisonitrile (MIBI) SPECT/CT in Affiliated Jiangyin Hospital of Nantong University were retrospectively analyzed. The AoAC volume was measured by Volume software of SPECT/CT system. The patients were divided into HBS group and non-HBS group, and the independent-sample t test, Mann-Whitney U test were used to compare differences of various indicators between the two groups. Logistic regression was used to analyze the influencing factors of HBS. Results:All 89 patients underwent PTX successfully, 50 patients (56.2%) were with HBS and 39 patients (43.8%) were not. The differences of age ((47.9±9.9) vs (56.1±9.0) years, t=-3.98, P<0.001), AoAC volume (0.36(0.02, 1.30) vs 1.57(0.37, 3.77)cm 3, Z=-3.17, P=0.002), preoperative alkaline phosphatase (ALP) (345.75(218.50, 632.50) vs (203.13±114.57)U/L, Z=-4.69, P<0.001), preoperative parathyroid hormone (147.85(109.83, 227.40) vs (135.58±51.14)pmol/L, Z=-2.34, P=0.019) and preoperative serum corrected calcium ((2.38±0.21) vs 2.54(2.39, 2.62)mmol/L, Z=-3.09, P=0.002) between HBS group and non-HBS group were significant. Logistic regression analysis showed that the AoAC volume ((odds ratio, OR)=0.628, 95% CI: 0.427-0.924, P=0.018), preoperative ALP ( OR=1.007, 95% CI: 1.002-1.012, P=0.010) and preoperative serum corrected calcium ( OR=0.041, 95% CI: 0.003-0.545, P=0.016) were independent risk factors for HBS. Conclusion:The AoAC volume measured by preoperative SPECT/CT can be used for an effective criteria of evaluating HBS in patients with renal SHPT after PTX, and AoAC volume may be one of independent risk factors for HBS.

Objective:To investigate the relationship of the number and morphological of parathyroid glands on 99Tc m-methoxyisobutylisonitrile (MIBI) SPECT/CT with hungry bone syndrome (HBS) in patients with renal secondary hyperparathyroidism (SHPT) after parathyroidectomy (PTX). Methods:Eighty renal SHPT patients (46 males, 34 females; age (50.3±11.0) years) who underwent PTX between January 2018 and June 2024 were retrospectively analyzed in Affiliated Jiangyin Hospital of Nantong University. The number of parathyroid glands detected on SPECT/CT, diameter of parathyroid gland and its volume were recorded and measured. Patients were divided into HBS group and non-HBS group. Independent-sample t test, Mann-Whitney U test and χ2 test were used to compare differences of various indicators between those 2 groups. Multivariate logistic regression was used to analyze influencing factors of HBS. Results:HBS group included 45 patients and the rest 35 patients belonged to non-HBS group. Age ( t=-3.61, P=0.001), preoperative alkaline phosphatase (ALP) ( Z=-4.65, P<0.001), preoperative parathyroid hormone ( Z=-2.34, P=0.019) and preoperative serum corrected calcium ( t=-2.71, P=0.008) were all significantly different between HBS group and non-HBS group. Patients with the number of parathyroid glands≥4 detected by SPECT/CT were more in HBS group than those in non-HBS group (82.2%(37/45) vs 51.4%(18/35); χ2=8.87, P=0.003), and the total volume of parathyroid glands (2.56(1.93, 4.44) vs 2.00(1.18, 2.94)cm 3;Z=-2.25, P=0.024) and the maximum diameter of parathyroid glands ((17.71±3.78) vs (15.87±3.91) mm; t=2.14, P=0.036) were significantly different between those 2 groups. Logistic regression analysis showed that preoperative ALP (odds ratio ( OR)=1.008, 95% CI: 1.002-1.014, P=0.015), preoperative serum corrected calcium ( OR=0.017, 95% CI: 0.000-0.869, P=0.042) and the number of parathyroid gland≥4 detected by SPECT/CT ( OR=4.156, 95% CI: 1.038-16.642, P=0.044) were independent influencing factors for HBS. The sensitivity of the number of parathyroid glands≥4 detected by SPECT/CT for diagnosing HBS was 82.2%(37/45). Conclusion:The number of parathyroid glands≥4 detected by SPECT/CT is an independent influencing factor for HBS, with high diagnostic sensitivity for HBS, thus having good clinical value.

BACKGROUND: Arsenic trioxide (ATO) is indicated as a broad-spectrum medicine for a variety of diseases, including cancer and cardiac disease. While the role of ATO in hepatic ischemia/reperfusion injury (HIRI) has not been reported. Thus, the purpose of this study was to identify the effects of ATO on HIRI. METHODS: In the present study, we established a 70% hepatic warm I/R injury and partial hepatectomy (30% resection) animal models in vivo and hepatocytes anoxia/reoxygenation (A/R) models in vitro with ATO pretreatment and further assessed liver function by histopathologic changes, enzyme-linked immunosorbent assay, cell counting kit-8, and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) assay. Small interfering RNA (siRNA) for extracellular signal-regulated kinase (ERK) 1/2 was transfected to evaluate the role of ERK1/2 pathway during HIRI, followed by ATO pretreatment. The dynamic process of autophagic flux and numbers of autophagosomes were detected by green fluorescent protein-monomeric red fluorescent protein-LC3 (GFP-mRFP-LC3) staining and transmission electron microscopy. RESULTS: A low dose of ATO (0.75 μmol/L in vitro and 1 mg/kg in vivo ) significantly reduced tissue necrosis, inflammatory infiltration, and hepatocyte apoptosis during the process of hepatic I/R. Meanwhile, ATO obviously promoted the ability of cell proliferation and liver regeneration. Mechanistically, in vitro  studies have shown that nontoxic concentrations of ATO can activate both ERK and phosphoinositide 3-kinase-serine/threonine kinase (PI3K-AKT) pathways and further induce autophagy. The hepatoprotective mechanism of ATO, at least in part, relies on the effects of ATO on the activation of autophagy, which is ERK-dependent. CONCLUSION Low, non-toxic doses of ATO can activate ERK/PI3K-AKT pathways and induce ERK-dependent autophagy in hepatocytes, protecting liver against I/R injury and accelerating hepatocyte regeneration after partial hepatectomy.
Animals ; Arsenic Trioxide ; Autophagy/physiology* ; Reperfusion Injury/prevention & control* ; Mice ; Male ; Proto-Oncogene Proteins c-akt/physiology* ; Arsenicals/therapeutic use* ; Oxides/therapeutic use* ; Liver/metabolism* ; Extracellular Signal-Regulated MAP Kinases/metabolism* ; Mice, Inbred C57BL

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 access the relation of aortic arch calcification (AoAC) volume based on parathyroid SPECT/CT imaging with hungry bone syndrome (HBS) in patients with renal secondary hyperparathyroidism (SHPT) after parathyroidectomy (PTX).Methods:From June 2015 to May 2024, the imaging and clinical data of 89 renal SHPT patients (52 males, 37 females, age: (51.5±10.3) years) who underwent parathyroid 99Tc m-methoxyisobutylisonitrile (MIBI) SPECT/CT in Affiliated Jiangyin Hospital of Nantong University were retrospectively analyzed. The AoAC volume was measured by Volume software of SPECT/CT system. The patients were divided into HBS group and non-HBS group, and the independent-sample t test, Mann-Whitney U test were used to compare differences of various indicators between the two groups. Logistic regression was used to analyze the influencing factors of HBS. Results:All 89 patients underwent PTX successfully, 50 patients (56.2%) were with HBS and 39 patients (43.8%) were not. The differences of age ((47.9±9.9) vs (56.1±9.0) years, t=-3.98, P<0.001), AoAC volume (0.36(0.02, 1.30) vs 1.57(0.37, 3.77)cm 3, Z=-3.17, P=0.002), preoperative alkaline phosphatase (ALP) (345.75(218.50, 632.50) vs (203.13±114.57)U/L, Z=-4.69, P<0.001), preoperative parathyroid hormone (147.85(109.83, 227.40) vs (135.58±51.14)pmol/L, Z=-2.34, P=0.019) and preoperative serum corrected calcium ((2.38±0.21) vs 2.54(2.39, 2.62)mmol/L, Z=-3.09, P=0.002) between HBS group and non-HBS group were significant. Logistic regression analysis showed that the AoAC volume ((odds ratio, OR)=0.628, 95% CI: 0.427-0.924, P=0.018), preoperative ALP ( OR=1.007, 95% CI: 1.002-1.012, P=0.010) and preoperative serum corrected calcium ( OR=0.041, 95% CI: 0.003-0.545, P=0.016) were independent risk factors for HBS. Conclusion:The AoAC volume measured by preoperative SPECT/CT can be used for an effective criteria of evaluating HBS in patients with renal SHPT after PTX, and AoAC volume may be one of independent risk factors for HBS.