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 investigate the effect of colquhounia root tablet(CRT)on hyperglucose-in-duced epithelial-mesenchymal transition(EMT)in renal tubular epithelial cells(HK-2),and to explore its possible action mechanism.Methods HK-2 was cultured in vitro,and HK-2 was divided into the following five groups:control group(CON group),hyperosmolar group(MA group),high glucose group(HG group),high sugar+CRT group(HG+CRT group),high sugar+phosphatidylinositol 3 kinase inhibitor group(HG+LY29400 group),high sugar+CRT+phosphatidylinositol 3 kinase inhibitor group(HG+CRT+LY29400).The real time immunofluorescence quantitative PCR(qPCR)was used to detect the mRNA ex-pression levels of E-cadherin,α-smooth muscle actin(α-SMA)and phosphatase and tensin homolog(PTEN)in each group.Western-blot was used to detect the protein expression levels of PTEN,phosphatidylinositol 3 kinase(PI3K),protein kinase B(Akt),phosphorylated protein kinase B(p-Akt),E-cadherin and α-SMA in each group.Results Compared with the CON group,the protein and mRNA expression levels of α-SMA,p-Akt protein expression level and p-Akt/Akt ratio in the HG group were increased,the protein and mRNA ex-pression levels of E-cadherin and PTEN were decreased,and the differences were statistically significant(P＜0.05).Compared with the HG group,the α-SMA protein and mRNA expression levels in the HG+CRT group were decreased,while the E-cadherin protein and mRNA expression levels were increased,and the differences were statistically significant(P＜0.05).Compared with the HG+CRT group,there was no significant differ-ence in the E cadherin,α SMA,PTEN,P13K and Akt protein expression levels and p-Akt/Akt ratio in the HG+CRT+LY29400 group had no significant differences(P＞0.05).while the expression level of p-Akt protein was increased,and the difference was statistically significant(P＜0.05).Conclusion In vitro,CRT could re-verse hyperglucose-induced renal tubular epithelial cell EMT via the PTEN/PI3K/Akt signaling pathway.

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 observe the value of CT"cut-edge sign"for differentiating complex thymic cyst and thymic epithelial tumor(TET)with diameter less than 4 cm.Methods Data of 24 patients with complex thymic cyst(complex thymic cyst group)and 14 patients with TET(TET group)confirmed by surgical pathology who underwent plain and dual-phase enhanced chest CT scanning were retrospectively analyzed.CT"cut-edge sign"was evaluated by 2 physicians,and the inter-observer consistency was evaluated using intra-class correlation coefficient(ICC).The detection rate of CT"cut-edge sign"was compared between groups using logistic regression analysis.Receiver operating characteristic(ROC)curve was drawn,and the area under the curve(AUC)was calculated to evaluate the efficacy of CT"cut-edge sign"for differentiating complex thymic cyst and TET.Results The inter-observer consistency of CT"cut-edge sign"was good(ICC=0.94,95％CI[0.90,0.97]).The detection rate of CT"cut-edge sign"in complex thymic cyst group was 62.50％(15/24),higher than in TET group(2/14,14.29％)(P＜0.01).The sensitivity,specificity,accuracy and AUC of CT"cut-edge sign"for differentiating complex thymic cyst and TET was 62.50％(15/24),85.71％(12/14),71.05％(27/38)and 0.74,respectively.Conclusion CT"cut-edge sign"was helpful for differentiating complex thymic cyst and TET with diameter less than 4 cm.

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 analyze the reports of neurocognitive adverse events caused by evolocumab and alirocumab，so as to provide reference for clinical safe drug use . METHODS From July 1，2015 to September 30，2020，the neurocognitive adverse event reports of evolocumab and alirocumab in the FDA adverse event reporting system （FAERS） were extracted ，and the neurocognitive adverse events were identified using high -level phrases . The reported odds ratio （ROR）method was used to evaluate the correlation between the above two drugs and neurocognitive impairment according to the setting of the number of reports ≥3 and the lower limit of the 95% confidence interval （95%CI）of ROR ＞1. RESULTS Totally 71 849 and 13 171 reports of adverse events were obtained for evolocumab and alirocumab respectively，of which 1 425（1.98%）and 405（3.07%）were reported for neurocognitive adverse events . ROR（95%CI）of neurocognitive adverse events caused by evolocumab and alirocumab were 0.610 （0.579，0.643）and 0.931（0.844，1.028），respectively. One signal （memory impairment ）was screened by evolocumab ，and three signals（memory impairment ，amnesia and cognitive impairment ）were screened by alirocumab. CONCLUSIONS There is no risk of neurocognitive impairment in patients receiving evolocumab and alicizumab .

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.

Objective:To compare the biomechanical performance between 5 internal fixation methods for fracture of the acetabular posterior column using finite element analysis.Methods:One healthy female volunteer (50 years old, 160 cm in height and 63 kg in weight with a body mass index of 24.6 kg/m 2) was recruited for this study to undergo CT scan. Her CT scan data were imported into software Mimics15.0 in the format of DICOM to generate a 3D model of the pelvis. After pre-processing and accessory ligament structures added, a 3D finite element model of the pelvis was established and verified by software ANSYS. Next, software ANSYS was used to generate a model of acetabular posterior column fracture, on which models of 5 internal fixation methods (internal iliac-ischial plating, conventional posterior column plating, anterograde tensile screwing, lesser sciatic notch screwing and ischial tuberosity screwing) were established. Then stress was loaded onto the 5 internal fixation models to compare stress displacements of the fracture line on the articular surface and sites of stress concentration between the 5 internal fixation models. Results:The average stress displacement of the fracture line at the standing position was 6.13 μm for conventional posterior column plating, <6.85 μm for ischial tuberosity screwing, <7.07 μm for lesser sciatic notch screwing, <7.08 μm for internal iliac-ischial plating, and <7.85 μm for anterograde tensile screwing; the average stress displacement of the fracture line at the sitting position was 7.77 μm for conventional posterior column plating, <9.65 μm for internal iliac-ischial plating, <9.69 μm for anterograde tensile screwing,<10.1 μm for lesser sciatic notch screwing, and<10.20 μm for ischial tuberosity screwing. In all the 5 internal fixation models, the stress was chiefly concentrated at fracture ends.Conclusion:Internal iliac-ischial plating and conventional posterior column plating provide better stability than the hollow screws (anterograde tensile screwing, ischial tuberosity screwing and lesser sciatic notch screwing) for fracture of the acetabular posterior column.

De novo variants (DNVs) are one of the most significant contributors to severe earlyonset genetic disorders such as autism spectrum disorder, intellectual disability, and other developmental and neuropsychiatric (DNP) disorders. Presently, a plethora of DNVs have been identified using next-generation sequencing, and many efforts have been made to understand their impact at the gene level. However, there has been little exploration of the effects at the isoform level. The brain contains a high level of alternative splicing and regulation, and exhibits a more divergent splicing program than other tissues. Therefore, it is crucial to explore variants at the transcriptional regulation level to better interpret the mechanisms underlying DNP disorders. To facilitate a better usage and improve the isoform-level interpretation of variants, we developed NeuroPsychiatric Mutation Knowledge Base (PsyMuKB). It contains a comprehensive, carefully curated list of DNVs with transcriptional and translational annotations to enable identification of isoformspecific mutations. PsyMuKB allows a flexible search of genes or variants and provides both table-based descriptions and associated visualizations, such as expression, transcript genomic structures, protein interactions, and the mutation sites mapped on the protein structures. It also provides an easy-to-use web interface, allowing users to rapidly visualize the locations and characteristics of mutations and the expression patterns of the impacted genes and isoforms. PsyMuKB thus constitutes a valuable resource for identifying tissue-specific DNVs for further functional studies of related disorders. PsyMuKB is freely accessible at http://psymukb.net.

Objective To investigate the iodine intake level and the prevalence of thyroid nodules in Harbin City,and to study the correlation between the concentration of urinary iodine and the prevalence of thyroid nodules.Methods In Harbin,18 communities were randomly selected and specimens were collected from fasting morning urine from 2015 to 2017.The urine iodine concentration (UIC) was detected by arsenic cerium catalytic spectrophotometry,and the thyroid nodule was examined by B ultrasound.Results A total of 2 552 residents aged (45.79 ± 12.06) years old agreed to participate in the study,including 371 males and 2 181 females.The median UIC in all participants was 159.8 μg/L,there was a significant difference in urine iodine frequency distribution among age groups (x2 =40.097,P ＜ 0.01).Furthermore,the median UIC in male was 166.6 μg/L,and in female was 156.2 μg/L.There was a significant difference in UICs between male and female (U =2.122,P ＜ 0.05).The prevalence of total thyroid nodules in all participants was 48.75％ (1 244/2 552),and the standardized rate was 40.55％.Significant difference in the detection rate of thyroid nodules was observed among age groups (x2 =114.922,P ＜ 0.01),and there was a positive and significant correlation between the detection rate of thyroid nodules and increasing age (xtrand =111.746,P ＜ 0.01).Furthermore,in male,41.24％ (153/371) had thyroid nodules,with standardized prevalence rate of 41.13％,and in female,50.02％ (1 091/2 181) had thyroid nodules,with standardized prevalence rate of 49.20％.Likewise,there was a significant difference in the detection rate of thyroid nodules between male and female(x2 =9.790,P ＜ 0.01).The detection rate of thyroid nodules in the iodine deficient population (urinary iodine was 0-＜ 100 μg/L) was 55.58％ (244/439),and the incidence of thyroid nodules in the iodine adequate or optimal population (urinary iodine was 100-＜ 200 μg/L) was 46.68％ (591/1 266).Conclusions The total iodine level of the population in Harbin City of Heilongjiang Province is at adequate level.The detection rate of thyroid nodules is high and it is increased with age.The detection rate of thyroid nodules is higher in female than male.Regular detection of urine iodine and adjusting iodine nutrition will help prevent thyroid nodules.