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 observe the role of the renin-angiotensin system in myocardial injury induced by experi-mental vascular dementia.Methods Eighteen adult male rats were categorized into a normal group,sham group,and modified 2-vessel occlusion group(model).To assess the myocardial injury caused by experimental vascular dementia,immunostaining was conducted to evaluate the interstitial collagen fraction and myocyte cross-sectional ar-ea.The concentrations of angiotensin Ⅱ(Ang Ⅱ)and angiotensin 1-7(Ang1-7)in the serum,as well as the ex-pression levels of angiotensin converting enzyme(ACE),angiotensin converting enzyme 2(ACE2),Ang Ⅱ,Ang1-7,angiotensin type 1(AT1)receptor,and Mas receptor in the myocardium,were assessed.Results Modified 2-vessel occlusion led to pronounced cognitive dysfunction(P＜0.01)and myocardial injury(P＜0.000 1)when compared to the sham and normal groups.Additionally,modified 2-vessel occlusion induced significant upregulation of the ACE/Ang Ⅱ/AT1 receptor axis(P＜0.01)and downregulation of the ACE2/Ang1-7/Mas axis(P＜0.05)of the renin-angiotensin system in the myocardium.Conclusion Myocardial injury in rats with experimental vascu-lar dementia may be related to dysregulation of the renin-angiotensin system.

Objective To discuss the detection rate of the arc of Bühler(AOB)in CTA and DSA examinations and its clinical significance.Methods A computerized retrieval of academic papers concerning AOB from the databases of PubMed,Web of Science,Scopus,Embase,Google Scholar,CBM,CNKI,WanFang,VIP and Baidu Scholar was conducted.Stata 17.0 software was used to make meta-analysis.Results A total of 11 articles including 3 837 subjects and 65 AOB cases were included in this analysis.The pooled prevalence of AOB was 1.9％(0.8％-3.2％).CTA showed a pooled prevalence of AOB of 2.0％(0.5％-4.3％)and DSA showed a pooled prevalence of AOB of 1.8％(0.5％-3.9％).Conclusion Clinically,AOB is a rarely-seen anatomical variation.The possibility of the presence of an AOB should be considered when performing the relevant abdominal surgery so as to avoid causing operation difficulties and complications such as abdominal visceral organ ischemia or bleeding.(J Intervent Radiol,2024,33:604-609)

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.

Enterotoxigenic Escherichia coli（ETEC）infection can induce watery diarrhea，leading to dehydration，electrolyte disturbance，and even death in severe cases. Recombinant B subunit/inactivated whole-cell cholera（rBS/WC）vaccine is effective in preventing ETEC infectious diarrhea. On the basis of the latest evidence on etiology and epidemiology of ETEC，as well as the effectiveness，safety，and health economics of rBS/WC vaccine，National Clinical Research Center for Child Health（The Children’s Hospital，Zhejiang University School of Medicine）and Zhejiang Provincial Center for Disease Control and Prevention invited experts to develop expert consensus on rBS/WC vaccine in prevention of ETEC infectious diarrhea. It aims to provide the clinicians and vaccination professionals with guidelines on using rBS/WC vaccine to reduce the incidence of ETEC infectious diarrhea.

Objective:To investigate the effects of sodium-glucose cotransporter 2 inhibitor dapagliflozin on myocardial remodeling in mice with diabetic cardiomyopathy and related mechanisms.Methods:Between January and December 2021, 60 6-week-old male C57BL/6J mice were chosen for the study, 40 were used to establish a diabetic cardiomyopathy model and the model was established in 28 mice, of whom, 14 were assigned to a non-intervention group and 14 to a dapagliflozin treatment group(intervention group).The rest of the 20 mice were in the control group.The mice in the intervention group were treated with dapagliflozin via oral gavage for 12 weeks.Cardiac structure and function were measured by ultrasound, the degree of myocardial fibrosis was evaluated by histology and electron microscopy, the concentrations of inflammatory factors were detected by enzyme-linked immunosorbent assays, apoptosis of myocardial cells was examined by terminal deoxynucleotidyl transferase mediated dUTP nick end labeling(TUNEL), and the level of myocardial oxidative stress was evaluated by dihydroethidium fluorescence.Results:At the end of the experiments, the body weight and fasting blood glucose in the intervention group were slightly lower than in the non-intervention group, but the difference was not statistically significant, while values from cardiac function parameters such as left ventricular ejection fraction were more favorable than in the non-intervention group[(61.07±4.66)% vs.(45.8±4.80)%, t=-5.24, P<0.05].Compared with the non-intervention group, the intervention group had alleviated myocardial hypertrophy, less myocardial disarray, and reduced collagen volume fraction[(18.4±1.9)% vs.(31.8±3.7)%, t=-12.0, P<0.05].Furthermore, the concentrations of inflammatory factors in the intervention group were lower than in the control group[interleukin-6: (82.19±10.90)ng/L vs.(291.02±31.02)ng/L, t=23.8, P<0.05; tumor necrosis factor-α: (70.45±12.13)ng/L vs.(201.31±27.10)ng/L( t=16.5), P<0.05; perforin 3: (13.05±2.04)μg/L vs.(42.40±1.26)μg/L( t=45.8), P<0.05; the index of myocardial apoptosis: 1.736±0.247 vs.0.864±0.129, t=11.7, P<0.05].The level of myocardial oxidative stress in the non-intervention group was higher than in the intervention group(2.655±0.252 vs.1.274±0.298, t=-13.3, P<0.05). Conclusions:Dapagliflozin can reduce myocardial hypertrophy and inhibit myocardial fibrosis through mitigating myocardial oxidative stress and inflammatory response, thus suppressing myocardial remodeling and ultimately protecting cardiac function in diabetic cardiomyopathy mice.

AIM: To investigate the mechanism of elemene synergistic bortezomib against multiple myeloma based on ROS-NF-κB-p38MAPK signaling pathway. METHODS: CCK-8 assay was used to detect cell activity. Nude mice were randomly divided into control group, bortezomib (BTZ) group, elemene (ELE) group and combination group. Each group was treated with BTZ, ELE and BTZ combined with ELE, respectively. Tunel staining was performed to observe the apoptosis of tumor tissues. The expressions of Caspase-3, Bcl-2, NF-κB and p38 MAPK were detected by Western Blot. Cell cycle, apoptosis and reactive oxygen species (ROS) expression were detected by flow cytometry using human myeloma U266 cells. RESULTS: When 4.0 μmol/L ELE combined with 50 nmol/L BTZ treated U266, the cell activity was significantly reduced compared with that of NC, BTZ and ELE groups (P< 0.05). The tumor volume of nude mice in BTZ group, ELE group and combined group was significantly reduced compared with the control group (P <0.05), and the combined group was the smallest. Tunel staining results showed that the apoptosis level in the control group was lower than that in the BTZ group, ELE group and the combined group (P<0.05), and the combined group had the lowest apoptosis level. Compared with the control group, the expressions of Caspase-3 and p38 MAPK in BTZ group, ELE group and combination group were significantly increased, while the expression of Bcl-2 was significantly decreased. The apoptosis level and expression of ROS in BTZ group, ELE group and the combined group was significantly increased compared with the control group (P<0.05). CONCLUSION: ELE can enhance the role of BTZ in promoting apoptosis of myeloma cells, which may be achieved by regulating ROS/NF-κB/p38 MAPK signaling pathway to enhance the level of apoptosis of tumor cells to achieve anti-tumor effect.

To investigate the cellular target selectivity of small molecules targeting thioredoxin reductase 1, we reported the construction and functional research of a stable TrxR1 gene (encode thioredoxin reductase 1) knockout HCT-116 cell line. We designed and selected TrxR1 knockout sites according to the TrxR1 gene sequence and CRISPR/Cas9 target designing principles. SgRNA oligos based on the selected TrxR1 knockout sites were obtained. Next, we constructed knockout plasmid by cloning the sgRNA into the pCasCMV-Puro-U6 vector. After transfection of the plasmid into HCT-116 cells, TrxR1 knockout HCT-116 cells were selected using puromycin resistance. The TrxR1 knockout efficiency was identified and verified by DNA sequencing, immunoblotting, TRFS-green fluorescent probe, and cellular TrxR1 enzyme activity detection. Finally, the correlation between TrxR1 expression and cellular effects of drugs specifically targeting TrxR1 was investigated by CCK-8 assay. The results demonstrated that the knockout plasmid expressing the sgRNA effectively knocked-out TrxR1 gene within HCT-116 cells, and no expression of TrxR1 protein could be observed in stable TrxR1 knockout HCT-116 (HCT116-TrxR1-KO) cells. The TrxR1-targeting inhibitor auranofin did not show any inhibitory activity against either cellular TrxR1 enzyme activity or cell proliferation. Based on these results, we conclude that a stable TrxR1 gene knockout HCT-116 cell line was obtained through CRISPR/Cas9 techniques, which may facilitate investigating the role of TrxR1 in various diseases.
CRISPR-Cas Systems/genetics* ; Gene Editing ; Gene Knockout Techniques ; HCT116 Cells ; Humans ; RNA, Guide/metabolism*

Objective:To explore the clinical and genetic characteristics of two children with a clinical diagnosis of Treacher Collins syndrome (TCS).Methods:Whole-exome sequencing was used to screen potential variants in the two children. Confirmation of suspected variants was performed through Sanger sequencing , multiplex ligation dependent probe amplification and real-time PCR in probands and their parents.Results:A heterozygous deletion variant, c. 4357_4360delGAAA, was detected in case one, while was de novo and verified by Sanger sequencing. Thevariant was classified as pathogenic(PVS1 + PM2+ PM6)according to ACMG guideline. The heterozygous deletion of exon 1-7 was seen in the same gene in case 2, which MLPA verified as heterozygous deletion of exon 1-6. This deletion was inherited from the father with a normal phenotype, and the father’s TCOF1 gene was suspected to be chimeric heterozygous deletion of exon 1-6 verified by MLPA. Conclusion:The identified variants in the TCOF1 gene probably underlie the two cases of TCS. There was no apparent correlation between genotype and phenotype. In addition, it shows a high interfamilial variability ranging from normal to full presentation of TCS. Genetic detection provided clinical diagnosis and genetic counselling for TCS patients .