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 explore the clinical application value of rapid next-generation sequencing (NGS) strategy based on targeted amplicon sequencing in the diagnosis of myeloid neoplasms.Methods:In this observational study, both rapid NGS and conventional NGS on the bone marrow or peripheral blood samples of 682 patients were prospectively performed from February 2021 to August 2022 in First Affiliated Hospital of Soochow University. The sequencing results were analyzed using the local Ion Reporter software and our lab′s self-built bioinformatics platform, respectively. The timeliness of the two sequencing platforms was compared, and the Kappa consistency test was used to evaluate the consistency between the two sequencing platforms. Patients aged between 18 and 59 years with newly diagnosed acute myeloid leukemia (AML) underwent screening by rapid NGS combining multiplex RT-PCR and in situ fluorescence hybridization technique within 72 hours, from whom high-risk patients according to European LeukemiaNet (ELN) 2017 were screened for individualized induction therapy.Results:In terms of timeliness, the median time from sample receipt to report issuance were 3 (2, 4) days and 13 (11, 15) days under rapid NGS and conventional NGS testing, respectively, with a statistically significant difference ( Z=?22.636, P<0.001). Among 682 specimens with a total of 1 507 variants, rapid NGS detected a total of 1 499 variants, with a detection rate of 99.5% and 674 cases were accurate, with an accuracy rate of 98.8%; the conventional NGS detected 1 506 variants, with a detection rate of 99.9% and 681 cases were accurate, with an accuracy rate of 99.9%. In 682 specimens, there were 181 negative and 501 positive, in which 8 cases were missed under rapid NGS, and 1 case was missed under conventional NGS. The kappa value was 0.967 by Kappa consistency test, and P<0.001, suggesting good consistency and consistency between the two NGS platforms. From February 2021 to July 2022, 286 patients who were rapidly diagnosed of AML contained 78 patients screened as the ELN 2017 adverse-risk category, including 42 patients enrolled, with age 39 (33, 52) years old. After one cycle of venetoclax combined with decitabine induction therapy, 78.6%(38/42) of the patients achieved composite complete remission. Among the rest 104 additional myeloid neoplasms, rapid NGS detected mutations in 80 patients, with a detection rate of 76.9%, among which 89.0%(215/242) of the variants could serve as the basis for the diagnostic classification, prognostic evaluation, and target therapy of myelodysplastic syndromes (MDS), myeloproliferative neoplasms (MPN), and myelodysplastic/myeloproliferative neoplasms (MDS/MPN). Conclusion:The rapid NGS based on targeted amplicon sequencing is in good consistency with conventional NGS, and shorters the diagnostic time, whose sensitivity and detection range meets the need for diagnostic classification, prognostic stratification, and target therapy of myeloid neoplasms.

Objective To study the effect and mechanism of paeonol(PAE)on renal interstitial fibrosis in rats.Methods The rats were randomly divided into sham operation(Sham)group,unilateral ureteral obstruction(UUO)group,PAE low dose(PAE-L)group,PAE medium dose(PAE-M)group,PAE high dose(PAE-H)group and irbesartan(IRB)group.Except for the Sham group,the UUO model was established in other groups.Each group was given a corresponding intervention for two weeks.Serum creatinine(Scr),blood urea nitrogen(BUN),serum 8-hydroxydeoxyguanosine(8-OHdG)levels,renal tissue superoxide dismutase(SOD),glutathione peroxidase(GPX)activities,α-smooth muscle actin(α-SMA),type Ⅰ collagen(Col-Ⅰ),fibronectin(FN),silent information regulator 1(SIRT1),nuclear factor E2-related factor 2(Nrf2)protein expression were detected;observe pathological changes of kidney tissue and calculate collagen volume fraction(CVF).Results Compared with the UUO group,the serum levels of Scr,BUN,and 8-OHdG in each dose group of PAE were decreased,the activities of SOD and GPX in kidney tissue were increased,the positive expressions of α-SMA,Col-Ⅰ and FN in kidney tissue were decreased,and the protein expressions of SIRT1 and Nrf2 were increased.Masson staining showed a decrease of CVF in renal tissue(all P<0.05),and HE staining showed a different degree of improvement in pathological changes such as inflammatory cell infiltration and tubular dilatation in renal tissue;PAE improves renal interstitial fibrosis in rats in a dose-dependent manner(P<0.05),and the effect of large dose PAE on renal interstitial fibrosis in rats was similar to that of IRB.Conclusion PAE can alleviate UUO-induced rat renal interstitial fibrosis and oxidative stress,and improve rat renal function.And this mechanism may be related to the activation of the SIRT1/Nrf2 signaling pathway.

Objective:To investigate the clinical characteristics and treatment of Beh?et′s disease complicated with cardiac valve involvement.Methods:We searched the wanfang medical database and Medline database to reviewed the domestic and foreign literature reports on cardiac Beh?et′s disease and analyzed their clinical features and therapeutic strategies. Chi-squared test was used for data analysis.Results:It was shown that Beh?et′s disease with cardiac valve involvement mainly affect men. The male to female ratio was 3.86∶1 in China and 2.50∶1 in foreign patients( χ2=1.32, P=0.251). The preoperative diagnosis rate was not high(60.3% in China, 57.1% abroad) ( χ2=0.13, P=0.716). Aortic valve and perivalvular lesions were the most common involved sites, of which aortic regurgitation was the most frequenty occurred, followed by mitral valve lesions. Glucocorticoids was still the main means treatment for medical(93/235 in China, 28/420 abroad), cyclophosphamide was more widely used in China(28/235), azathioprine was more widely used in foreign countries (12/42). Aortic replacement (AVR) was the mainly surgical approach, followed by artificial aortic valve replacement and left ventricular outflow tract plasty (Bentall).The incidence of postoperative perivalvular leakage or valve prolapse was higher with AVR than with Bentall(AVR 76.3%/Bentall 21.8% at home, χ2=32.60, P<0.001, AVR 71.4%/Bentall 0 abroad, χ2=13.84, P<0.001). Conclusions:Cardiac valve involvement is a severe complication of Beh?et′s disease. Heart involvement are more common, and the preoperative diagnosis rate is lower in China. The incidence of perivalve leakage (PVL) or valve prolapse (PD) after operation is higher with AVR than with Bentall surgery.The Bentall operation could improve prognosis and the postoperative complications abroad are lower than domestic.

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.

Objectives: . Despite the efficacy of surgical treatments, the high rate of recurrence in juvenile nasopharyngeal angiofibroma (JNA) after surgery remains an unresolved problem. The present study comprehensively analyzed the risk factors and characteristics of JNA recurrence, providing clinical guidance for reducing recurrence. Methods: . A total of 123 patients who underwent surgery for JNA between 1997 and 2019 at a single hospital were analyzed retrospectively. Univariate and multivariate analyses were used to assess the clinical risk factors for the recurrence of JNA. The relapse-free survival and annual cumulative recurrence rates were analyzed for subgroups defined according to clinical parameters. Results: . After screening, 78 of the 123 patients were included in the present study. The main risk factors associated with JNA recurrence included the year of diagnosis, tumor size, sphenoid bone invasion, Radkowski stage, surgical approach, and intraoperative bleeding. Importantly, the surgical approach and sphenoid bone invasion were independent prognostic factors affecting recurrence. Patients who underwent endoscopic surgery without sphenoid bone invasion exhibited longer relapse-free survival. In the present study, the overall cumulative recurrence rate of JNA was 38.7%, and recurrence occurred mainly in the first year after the initial surgery. Conclusion . Endoscopic surgery achieved better relapse-free survival in JNA patients, and patients with sphenoid bone invasion should be carefully explored to avoid residual JNA. The recurrence rate of JNA differed among subgroups defined based on clinical parameters and was highest in the first year after surgery. Computed tomography or magnetic resonance imaging, along with close follow-up, should be performed strictly within 1 year after the primary operation.

Objective:To explore the effect of leptin on B cells in patients with systemic lupus erythematosus (SLE).Methods:Peripheral blood mononuclear cells (PBMCs) were isolated from SLE patients, and then CD19 + B cells were purified with magnetic bead sorting method. PBMCs or purified B cells were cultured with recombinant leptin at 0, 100, 250 ng/ml for 3 or 5 days. The frequencies of plasma cells, follicular helper T (Tfh) cells and peripheral helper T (Tph) cells, as well as activation markers (CD80, CD86) and leptin receptor and the proliferation of B cells were determined with flow cytometry. The concentrations of antibodies and cytokines were examined with enzyme-linked immunosorbnent assay (ELISA). Data were analyzed with t test and analysis of variance (ANOVA). Results:Increased levels of leptin were positively correlated with systematic lupus erythematosus disease activity index (SLEDAI) and the frequency of plasma cells in SLE patients. Leptin receptor could be detected on SLE B cells, and recombinant leptin elevated the levels of its receptor on CD19 + B cells [(7.8±1.3)% vs (6.1±0.9)%, t=3.36, P=0.006]. Leptin enhanced the expression of CD80 [(21±4)% vs (19±4)%, t=2.84, P=0.004] and CD86 [(22±4)% vs (19±4)%, t=4.92, P=0.004] on SLE B cells in vitro. It also promoted B cells to differentiate into plasma cells [(7.6±1.5)% vs (5.2±1.3)%, t=6.42, P=0.025]. There was no statistical significant difference of the effect of leptin on B cell proliferation. Leptin also increased the levels of antibodies [IgG: (62±3) ng/ml vs (45±4) ng/ml, t=7.75, P<0.001; IgM: (112±24) ng/ml vs (56±18) ng/ml, t=5.38, P<0.001] and inflammatory cytokines [IL-6: (24±5) pg/ml vs (20±5) pg/ml, t=4.09, P=0.002; TNF-α: (19.1±3.8) pg/ml vs (14.1±2.9) pg/ml, t=3.38, P=0.006; IL-10: (24±5) pg/ml vs (20±5) pg/ml, t=4.09, P=0.002] secreted by B cells. In addition, leptin significantly upregulated the frequencies of Tfh cells[(2.82±0.49)% vs (1.28±0.20)%, t=4.56, P=0.001] and Tph cells [(4.5±0.5)% vs (3.4±0.4)%, t=3.88, P=0.003]. Conclusion:Leptin could directly promote the activation, differentiation and secretory capacity of B cells by binding to its receptor, and also modulate B cell responses indirectly via enhancement of Tfh and Tph cells, which may be involved in the pathogenesis of SLE.

Objective:To investigate the distribution and antimicrobial resistance profile of clinical bacteria isolated from blood culture in China.Methods:The clinical bacterial strains isolated from blood culture from member hospitals of Blood Bacterial Resistant Investigation Collaborative System (BRICS) were collected during January 2018 to December 2019. Antibiotic susceptibility tests were conducted with agar dilution or broth dilution methods recommended by US Clinical and Laboratory Standards Institute (CLSI). WHONET 5.6 was used to analyze data.Results:During the study period, 14 778 bacterial strains were collected from 50 hospitals, of which 4 117 (27.9%) were Gram-positive bacteria and 10 661(72.1%) were Gram-negative bacteria. The top 10 bacterial species were Escherichia coli (37.2%), Klebsiella pneumoniae (17.0%), Staphylococcus aureus (9.7%), coagulase-negative Staphylococci (8.7%), Pseudomonas aeruginosa (3.7%), Enterococcus faecium (3.4%), Acinetobacter baumannii(3.4%), Enterobacter cloacae (2.9%), Streptococci(2.8%) and Enterococcus faecalis (2.3%). The the prevalence of methicillin-resistant S. aureus (MRSA) and methicillin-resistant coagulase-negative Staphylococcus were 27.4% (394/1 438) and 70.4% (905/1 285), respectively. No glycopeptide-resistant Staphylococcus was detected. More than 95% of S. aureus were sensitive to amikacin, rifampicin and SMZco. The resistance rate of E. faecium to vancomycin was 0.4% (2/504), and no vancomycin-resistant E. faecalis was detected. The ESBLs-producing rates in no carbapenem-resistance E. coli, carbapenem sensitive K. pneumoniae and Proteus were 50.4% (2 731/5 415), 24.6% (493/2001) and 35.2% (31/88), respectively. The prevalence of carbapenem-resistance in E. coli and K. pneumoniae were 1.5% (85/5 500), 20.6% (518/2 519), respectively. 8.3% (27/325) of carbapenem-resistance K. pneumoniae was resistant to ceftazidime/avibactam combination. The resistance rates of A. baumannii to polymyxin and tigecycline were 2.8% (14/501) and 3.4% (17/501) respectively, and that of P. aeruginosa to carbapenem were 18.9% (103/546). Conclusions:The surveillance results from 2018 to 2019 showed that the main pathogens of bloodstream infection in China were gram-negative bacteria, while E. coli was the most common pathogen, and ESBLs-producing strains were in majority; the MRSA incidence is getting lower in China; carbapenem-resistant E. coli keeps at a low level, while carbapenem-resistant K. pneumoniae is on the rise obviously.

Objective:To investigate the bacterial composition and antimicrobial resistance profile of clinical isolates from bloodstream infections in China.Methods:The clinical bacterial strains isolated from blood culture were collected during January 2020 to December 2020 in member hospitals of Blood Bacterial Resistant Investigation Collaborative System (BRICS). Antibiotic susceptibility tests were conducted by agar dilution or broth dilution methods recommended by Clinical Laboratory Standards Institute(CLSI, USA). WHONET 5.6 was used to analyze data.Results:During the study period, 10 043 bacterial strains were collected from 54 hospitals, of which 2 664 (26.5%) were Gram-positive bacteria and 7 379 (73.5%) were Gram-negative bacteria. The top 10 bacterial species were Escherichia coli (38.6%), Klebsiella pneumoniae (18.4%), Staphylococcus aureus (9.9%), coagulase-negative Staphylococci (7.5%), Pseudomonas aeruginosa (3.9%), Enterococcus faecium (3.3%), Enterobacter cloacae (2.8%), Enterococcus faecalis (2.6%), Acinetobacter baumannii (2.4%) and Klebsiella spp (1.8%). The prevalence of methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-resistant coagulase-negative Staphylococcus aureus were 27.6% and 74.4%, respectively. No glycopeptide- and daptomycin-resistant Staphylococci were detected. More than 95% of Staphylococcus aureus were sensitive to rifampicin and SMZco. No vancomycin-resistant Enterococci strains were detected. Extended spectrum β-lactamase (ESBL) producing Escherichia coli, Klebsiella pneumoniae and Proteus mirabilis were 48.4%, 23.6% and 36.1%, respectively. The prevalence rates of carbapenem-resistance in Escherichia coli and Klebsiella pneumoniae were 2.3% and 16.1%, respectively; 9.6% of carbapenem-resistant Klebsiella pneumoniae strains were resistant to ceftazidime/avibactam combination. The prevalence rate of carbapenem-resistance in Acinetobacter baumannii was 60.0%, while polymyxin and tigecycline showed good activity against Acinetobacter baumannii. The prevalence rate of carbapenem-resistance of Pseudomonas aeruginosa was 23.2%. Conclusions:The surveillance results in 2020 showed that the main pathogens of bloodstream infection in China were gram-negative bacteria, while Escherichia coli was the most common pathogen, and ESBL-producing strains declined while carbapenem-resistant Klebsiella pneumoniae kept on high level. The proportion and the prevalence of carbapenem-resistant Pseudomonas aeruginosa were on the rise slowly. On the other side, the MRSA incidence got lower in China, while the overall prevalence of vancomycin-resistant Enterococci was low.