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.

Objective:To report the results of national surveillance on the distribution and antimicrobial resistance profile of clinical Gram-positive bacteria isolates from bloodstream infections in China in 2022.Methods:The clinical isolates of Gram-positive 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:A total of 3 163 strains of Gram-positive pathogens were collected from 51 member units，and the top five bacteria were Staphylococcus aureus（ n=1 147，36.3%），coagulase-negative Staphylococci（ n=928，29.3%）， Enterococcus faecalis（ n=369，11.7%）， Enterococcus faecium（ n=296，9.4%）and alpha-hemolyticus Streptococci（ n=192，6.1%）. The detection rates of methicillin-resistant Staphylococcus aureus（MRSA）and methicillin-resistant coagulase-negative Staphylococci（MRCNS）were 26.4%（303/1 147）and 66.7%（619/928），respectively. No glycopeptide and daptomycin-resistant Staphylococci were detected. The sensitivity rates of Staphylococcus aureus to cefpirome，rifampin，compound sulfamethoxazole，linezolid，minocycline and tigecycline were all >95.0%. Enterococcus faecium was more prevalent than Enterococcus faecalis. The resistance rates of Enterococcus faecium to vancomycin and teicoplanin were both 0.5%（2/369），and no vancomycin-resistant Enterococcus faecium was detected. The detection rate of MRSA in southern China was significantly lower than that in other regions（ χ2=14.578， P=0.002），while the detection rate of MRCNS in northern China was significantly higher than that in other regions（ χ2=15.195， P=0.002）. The detection rates of MRSA and MRCNS in provincial hospitals were higher than those in municipal hospitals（ χ2=13.519 and 12.136， P<0.001）. The detection rates of MRSA and MRCNS in economically more advanced regions（per capita GDP≥92 059 Yuan in 2022）were higher than those in economically less advanced regions（per capita GDP<92 059 Yuan）（ χ2=9.969 and 7.606， P=0.002和0.006）. Conclusions:Among the Gram-positive pathogens causing bloodstream infections in China， Staphylococci is the most common while the MRSA incidence decreases continuously with time；the detection rate of Enterococcus faecium exceeds that of Enterococcus faecalis. The overall prevalence of vancomycin-resistant Enterococci is still at a low level. The composition ratio of Gram-positive pathogens and resistant profiles varies slightly across regions of China，with the prevalence of MRSA and MRCNS being more pronounced in provincial hospitals and areas with a per capita GDP≥92 059 yuan.

Objective:To report the results of national surveillance on the distribution and antimicrobial resistance profile of clinical bacterial isolates from bloodstream infections in China in 2021.Methods:The clinical bacterial strains isolated from blood culture from member hospitals of Blood Bacterial Resistant Investigation Collaborative System (BRICS) were collected during January 2021 to December 2021. Antibiotic susceptibility tests were conducted by agar dilution or broth dilution methods recommended by Clinical Laboratory Standards Institute (CLSI). WHONET 5.6 was used to analyze data.Results:During the study period, 11 013 bacterial strains were collected from 51 hospitals, of which 2 782 (25.3%) were Gram-positive bacteria and 8 231 (74.7%) were Gram-negative bacteria. The top 10 bacterial species were Escherichia coli (37.6%), Klebsiella pneumoniae (18.9%), Staphylococcus aureus (9.8%), coagulase-negative Staphylococci (6.3%), Pseudomonas aeruginosa (3.6%), Enterococcus faecium (3.6%), Acinetobacter baumannii (2.8%), Enterococcus faecalis (2.7%), Enterobacter cloacae (2.5%) and Klebsiella spp (2.1%). The prevalence of methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-resistant coagulase-negative Staphylococcus aureus were 25.3% and 76.8%, respectively. No glycopeptide- and daptomycin-resistant Staphylococci was detected; more than 95.0% of Staphylococcus aureus were sensitive to ceftobiprole. No vancomycin-resistant Enterococci strains were detected. The rates of extended spectrum B-lactamase (ESBL)-producing isolated in Escherichia coli, Klebsiella pneumoniae and Proteus mirabilis were 49.6%, 25.5% and 39.0%, respectively. The prevalence rates of carbapenem-resistance in Escherichia coli and Klebsiella pneumoniae were 2.2% and 15.8%, respectively; 7.9% of carbapenem-resistant Klebsiella pneumoniae was resistant to ceftazidime/avibactam combination. Ceftobiprole demonstrated excellent activity against non-ESBL-producing Escherichia coli and Klebsiella pneumoniae. Aztreonam/avibactam was highly active against carbapenem-resistant Escherichia coli and Klebsiella pneumoniae. The prevalence rate of carbapenem-resistance in Acinetobacter baumannii was 60.0%, while polymyxin and tigecycline showed good activity against Acinetobacter baumannii (5.5% and 4.5%). The prevalence of carbapenem-resistance in Pseudomonas aeruginosa was 18.9%. Conclusions:The BRICS surveillance results in 2021 shows that the main pathogens of blood stream infection in China are gram-negative bacteria, in which Escherichia coli is the most common. The MRSA incidence shows a further decreasing trend in China and the overall prevalence of vancomycin-resistant Enterococci is low. The prevalence of Carbapenem-resistant Klebsiella pneumoniae is still on a high level, but the trend is downwards.

Objective:To evaluate the role of nucleotide-binding oligomerization domain-2 (NOD2) in dorsal root ganglion in the development of neuropathic pain (NP) in rats.Methods:Thirty-two adult male SPF Sprague-Dawley rats, weighing 240-260 g, aged 2-3 months, were divided into 4 groups ( n=8 each) using a random number table method: control group (group C), NP group (group S), negative control siRAN group (group N), and NOD2-siRNA group (group R). In N and R groups, 1×10 8 IFU/ml negative control siRNA and NOD2-siRNA 10 μl were intrathecally injected, respectively, once a day for 3 consecutive days.Normal saline 10 μl was intrathecally injected once a day for 3 consecutive days in C and S groups.The model of NP was established using spared nerve injury (SNI) at 2 weeks after intrathecal injection.The mechanical paw withdrawal threshold (MWT) was measured at 1 day before surgery and 1, 3, 7, 10, 14 and 28 days after SNI.Animals were sacrificed after measuring pain threshold on day 28, and the dorsal root ganglions (DRGs) of the lumbar segment (L 4-6) were removed for determination of the expression of NOD2 (by Western blot) and expression of tumor necrosis factor-alpha (TNF-α), interleukin-1beta (IL-1β), IL-6 and NOD2 mRNA (using quantitative real-time polymerase chain reaction). Results:Compared with group C, MWT was significantly decreased at each time point after SNI, and the expression of NOD2 protein and mRNA and TNF-α, IL-1β and IL-6 mRNA in DRGs was up-regulated in group NP ( P<0.01). Compared with group NP, MWT was significantly increased at each time point after SNI, and the expression of NOD2 protein and mRNA and TNF-α, IL-1β and IL-6 mRNA in DRGs was down-regulated in group R ( P<0.01), and no significant change was found in the parameters mentioned above in group N ( P>0.05). Conclusion:The mechanism underlying the development of NP may be related to the up-regulation of NOD2 expression in DRGs, thus further promoting the expression of pro-inflammatory factors in rats.

Objective:To evaluate the efficacy and safety profile of ixazomib/lenalidomide/dexamethasone (IRd) in Chinese patients with relapsed/refractory multiple myeloma (MM) .Methods:This study comprising 14 medical centers in China included patients with relapsed/refractory MM who received at least. Ixazomib at an initial oral dose of 4 mg was administered. Seven patients had dose adjustment to 3 mg at the time of first dose. The lenalidomide doses were adjusted according to creatinine clearance rate. The efficacy and safety were evaluated every cycle.Results:In the study cohort of 74 patients, the median age was 65 years and 11 (14.9% ) patients received over three lines of therapy. Overall response rate (ORR) was 54.1% (40/74) , and 7 (9.5% ) , 14 (18.9% ) , and 19 (25.7% ) patients achieved stringent complete response or complete response, very good partial response, and partial response, respectively. The median progression-free survival and overall survival were 9.9 and 20 months, respectively. The median time to response was 1 month. The efficacy and survival outcome were similar to those reported in the Tourmaline-MM1 China Continuous Study. The ORR of patients refractory to bortezomib, lenalidomide, and bortezomib plus lenalidomide were 52.0% (13/25) , 57.1% (4/7) , and 33.3% (6/18) , respectively. The rate of grade 3-4 adverse events was 36.5% (27/74) . Common hematological toxicities were anemia, thrombocytopenia, lymphopenia, and neutropenia. Common non-hematological toxicities were fatigue, gastrointestinal symptoms, and infections. Two cases of grade 3 peripheral neuropathy were reported. The patients eligible for the Tourmaline-MM1 China Continuous Study had a higher ORR than the ineligible patients [77.8% (14/18) vs 46.4% (26/56) , P=0.020]. There was no difference in the rate of grade 3-4 adverse events [33.3% (6/18) vs 37.5% (21/56) , P=0.749]. Conclusion:The IRd regimen had good efficacy and acceptable toxicity in Chinese patients with relapsed/refractory MM.

Objective To study the correlation between the clinical characteristics of HCC patients with different phenotype circulating tumor cells in the peripheral blood.Methods 77 patients with HCC and 21 patients with benign liver diseases treated at Zhujiang Hospital of Southern Medical University from April 2015 to December 2016 were retrospectively studied.The CanPatrolTM System was adoptedto detect epithelial-mesenchymal phenotype CTCs in the peripheral blood.This study aimed to clarify whether the epithelial-mesenchymal phenotype CTCs were specifically originated from the tumorand to investigate the correlation between CTCs and the clinical features of the patients.Results Using epithelial and mesenchymal markers,the CTCs were divided into three subtypes:epithelial,mesenchymal and mixed CTCs.No epithelial-mesenchymal phenotype CTCs were detected in patients with benign liver diseases.The positivity rates of epithelial,mixed and mesenchymal CTCs in the peripheral blood of 77 patients with HCC were 37.7％ (29/77),74.0％ (57/77) and 50.6％ (39/77),respectively.The positivity rates of epithelial-mesenchymal phenotype CTCs in patients with HCC were significantly higher than the group of patients with benign liver diseases (P ＜ 0.05).The positivity rates of epithelial CTCs were significantly correlated with AFP,number of tumor and portal vein tumor thrombus (P ＜ 0.05).The positivity rates of mixed CTCs were significantly correlated with portal vein tumor thrombus,tumor differentiation and BCLC stage (P ＜ 0.05).The positivity rates of mesenchymal CTCs were significantly correlated with tumor size,portal vein tumor thrombus,tumor differentiation and BCLC stage (P ＜ 0.05).Conclusions The positivity rates of epithelial,mixed and mesenchymal CTCs were closely related to different aspects of clinical characteristics of patients with HCC.These CTCs may serve as indicatorsto evaluatethe progress of HCC.

Objective To evaluate the changes in natural Killer (NK) cell subsets definetd by CD11b and CD27 in the spleen of septic mice.Methods A total of 168 pathogen-free healthy male C57BL/6 mice,weighing 20-30 g,aged 8-10 weeks,were divided into 2 groups (n=84 cach) using a random number table:sham operation group (Sham group) and sepsis group (Sep group).Sepsis was induced by cecal ligation and puncture in chloral hydrate-anesthetized mice.Thirty mice in each group were selected to assess the survival within 4 days after operation,and the survival rate was calculated.At 2,4,6,24,48 and 72 h after operation (T1-6),6 mice were randomly selected,and blood samples were taken from the eyeballs for determination of serum tumor necrosis factor-alpha and interleukin-10 concentrations by enzyme-linked immunosorbent assay.Six mice were randomly selected at T4-6 and sacrificed,and the spleens were removed for measurement of the percentage of NK cells and their subsets by flow cytometry.Results Compared with Sham group,the survival rate was significantly decreased at different time points,the serum necrosis factor-alpha concentration at T1-3,6 and serum interleukin-10 concentration at T3-6 were increased,the percentage of NK cells was decreased at T4-6,the percentage of CD27-CD11b+NK cells was decreased and the percentage of CD27+CD11b+ and CD27+CD11b-NK cells was increased at T5,the percentage of CD27-CD11b-NK ceils was decreased at T4,5,and the percentage of CD27-CD11b-NK cells was increased at T6 in Sep group (P＜0.05).Conclusion Changes in NK cell subsets defined by CD11b and CD27 in the spleen play an important role in the development of sepsis in mice.

Objective To investigate the metabolism change of intestinal flora due to chronic hypoxia in infants. Methods Ten infants with tetralogy of fallot were considered as the chronic hypoxia group,10 healthy infants were regarded as the control group. The urine concen-tration of hippurate in the morning with fasting was detected by 1 H nuclear magnetic resonance. Results The concentration of hippurate was decreased in hypoxia group compared with the control group,(47. 15 ± 32. 88) mg/L vs (346. 698 ± 13. 555) mg/L,with significant differ-ence,P=0. 002. Conclusion Chronic hypoxia alters metabolism of intestinal flora in infants.

Objective To analyze the clinical characteristic of Chinese autoimmune pancreatitis (AIP) patients.Methods All clinical data of 81 patients with a diagnosis of AIP in Shanghai Changhai Hospital from February 2005 to May 2012 were analyzed.Results The sex ratio was 7.1∶1 and the mean age was (57± 12) years old in 81 patients with AIP.Obstructive jaundice was the initial symptom in 51.9％ (42/81) patients.In patient receiving CT,focal and diffuse type accounted for 45 and 35 patients.respectively,and pseudocyst was the main manifestation in 1 patient,biliary tract was involved in 59(72.8％ ) patients,dilatation of main pancreatic duct was observed in 5 ( 11.1％ ) patients.In patients receiving PET-CT,diffuse increased Flourine-18 FDG uptake by the pancreas was found in 11 patients,focal increased uptake in 2patients,and significant extra-pancreatic uptake was found in 5 patients.The positive rate of serum IgG4,CA19-9,ss DNA,anti-nuclear antibody and ds-DNA antibody was 94.6％ (53/81),54.4％ (37/68),14.3％ (4/28),10.7％ (3/28),7.1％ (2/28),respectively.The pathological findings of H-E staining and IgG4 immunohistochemical analysis in 20 patients were consistent with lymphoplasmacytic sclerosing pancreatitis.Conclusions Type 1 AIP is the main subtype of AIP in China.Combining clinical symptoms,extra-pancreatic manifestations,imaging or nuclear medicine findings,serology,cytology or histology can effectively increase the correct diagnosis rate of AIP.

OBJECTIVE: To compare the difference in gene expression profiles between parental cell line and drug resistant cell line (CNE-1 and CNE-1/taxol) pre-treated or treated by drugs, and search for genes related to taxol resistance and reversal of taxol resistance phenotype. METHODS: cDNA microarray was used to detect the difference in gene expression profiles between 6 groups of cells. Combination of multiple filtering genes and detailed analysis of documented resistance genes were used to analyze the data. RESULTS: Through multiple filtering, 297 differentially expressed genes were screened. The expression of 17 genes was increased or decreased more than 5 folds in CNE-1/taxol compared with CNE-1.Through analyzing documented drug-resistant genes, MDR1 expression was not detected in each group. CYP1A1, one of P450 family members, was not expressed in CNE-1, but significantly increased expressions was found in CNE-1/taxol and these increased expressions were restored by cisplatin. The expression level of some members of tumor necrosis factor family was decreased in CNE-1/taxol and restored by cisplatin, including TNFAIP1, 3 and TNFRSF12A, 21. The differentially expressed members in the caspase family were caspase-4 and caspase-6. The expression of β-tubulin II was down-regulated in CNE-1/taxol. TSP1 was obviously down-regulated in CNE- 1/taxol compared with CNE-1, and a more significant down-regulation of TSP1 was found when treated by taxol. However, it was greatly up-regulated after cisplatin treatment in CNE-1/taxol. CONCLUSION Some genes are probably related to taxol resistance and reversal of taxol resistance in NPC cells: 297 differentially expressed genes detected by multiple filing, CYP1A1, some members of TNF family and another 17 genes whose differential expression is more than 5 folds between parental cell line and drug resistant cell line. Combination of multiple filtering genes and detailed analysis of documented resistance genes is a good method to study drug resistance and reversal of drug resistance in carcinoma cells.
Basic Helix-Loop-Helix Leucine Zipper Transcription Factors ; genetics ; Cell Line, Tumor ; Cytochrome P-450 CYP1A1 ; genetics ; Drug Resistance, Neoplasm ; genetics ; Gene Expression Regulation, Neoplastic ; Humans ; Nasopharyngeal Neoplasms ; pathology ; Oligonucleotide Array Sequence Analysis ; Paclitaxel ; pharmacology ; Proteins ; genetics ; Receptors, Tumor Necrosis Factor ; genetics ; TWEAK Receptor