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 explore the effects of hesperidin against human tongue squamous cell carcinoma Tca-8113 cells and explore its mechanism of action.Methods:Tca-8113 cells were cultured in vitro with different concentrations of hesperidin.MTT assay and flow cytometry were used to detect the cell proliferation and apoptosis respectively.The potential targets of hesperidin against Tca-8113 cells were studied by network pharmacology.The protein-protein interaction network(PPI)was constructed,gene ontology GO analy-sis,kyoto gene and genome baike encyclopedia(KEGG)enrichment analysis were performed.Q-PCR was used to detect the effect of different concentrations of hesperidin on the related mRNA expression level of Tca-8113 cells.The binding force of hesperidin to the core targets was predicted by molecular docking and a scoring function was used to judge the binding force.Results:Hesperidin inhibi-ted proliferation and promoted apoptosis of Tca-8113 cells(P＜0.05)in a dosedependant manner;KEGG enrichment analysis of the key gene targets involved in the regulation of oral squamous cell carcinoma by hesperidin may be related to PI3K-Akt,MAPK and Ras signaling pathways.Q-PCR results showed that the mRNA expression of MAPK8,HSP90AA1 and MAPK1(ERK2)were significantly different(P＜0.05).Molecular docking results showed that hesperidin had the strongest binding force with MAPK1(ERK2).Conclu-sion:Hesperidin may inhibit the proliferation and promote apoptosis of Tca-8113 cells by regulating Ras/Raf/MEK/ERK signaling pathway.

Objective For more focused prevention and management,this investigation examines the risk factors for multidrug resistant organisms(MDRO)infections in intensive care unit(ICU)patients.Methods Case-control studies and cohort studies of risk factors for MDRO infection in ICU patients were searched in the Embase,Website of Science,Cochrane Library,PubMed,CNKI,WanFang,and VIP databases from their start to October 26,2022.The Meta-analysis was carried out with RevMan 5.3.Results A total of 32 papers were included,with 10 985 cases studied,with the quality of the literature rated as moderate to high.The results of Meta-analysis of this study showed that gender[OR=1.21,95% CI=(1.08,1.36),P=0.002],ICU length of stay[WMD=5.36,95% CI=(3.99,6.73),P<0.000 01],total length of stay[WMD=8.96,95% CI=(6.51,11.41),P<0.000 01],hypertension[OR=1.33,95% CI=(1.10,1.60),P=0.003],abnormal renal function[OR=1.69,95% CI=(1.33,2.16),P<0.000 01],hypoproteinemia[OR=1.87,95% CI=(1.51,2.32),P<0.000 01],mechanical ventilation[OR=2.26,95% CI=(1.18,4.33),P=0.01],duration of mechanical ventilation[WMD=8.83,95% CI=(2.52,15.14),P=0.006],arteriovenous placement[OR=1.46,95% CI=(1.23,1.72),P<0.000 1],placement of urinary catheter[OR=1.71,95% CI=(1.25,2.36),P<0.000 01],gastrointestinal tube placement[OR=0.10,95% CI=(0.03,0.18),P=0.008],antimicrobial drug type≥3[OR=4.27,95% CI=(2.06,8.85),P<0.000 01],use of carbapenem antibiotics[OR=4.09,95% CI=(300,5.58),P<0.000 01],the use of the third-generation cephalosporin[OR=1.63,95% CI=(1.15,2.33),P=0.007],the use of quinolone antibacterials[OR=1.86,95% CI=(1.42,2.44),P<0.000 01],the use of aminoglycoside antibiotics[OR=1.99,95% CI=(1.49,2.67),P<0.000 01],use of piperacillin-tazobactam[OR=2.94,95% CI=(1.56,5.54),P=0.000 9],use of glycopeptide antibiotics[OR=3.78,95% CI=(2.48,5.78),P<0.000 01],use of sedatives[OR=3.25,95% CI=(2.06,5.14),P<0.000 01],and use of acid suppressants[OR=1.51,95% CI=(1.06,2.16),P=0.02]are risk factors for MDRO infection in ICU patients.Conclusion MDRO infections in ICU patients are associated with gender,duration of ICU stay,chronic lung disease,total length of stay,hypertension,abnormal renal function,hypoproteinemia,mechanical ventilation,duration of mechanical ventilation,arteriovenous placement,placement of urinary catheters,gastrointestinal placement,type of antimicrobial drugs≥3,use of carbapenem antibiotics,use of third-generation cephalosporin,use of quinolone antibacterials,use of aminoglycoside antibiotics,use of piperacillin-tazobactam,use of glycopeptide antibiotics,use of sedatives,use of acid suppressants,and other factors.Targeted controls of different factors such as underlying diseases,comorbidities,invasive procedures performed,and the use of antimicrobial medications and other therapeutic pharmaceuticals could limit the risk of infection in MDRO in ICU patients.

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 investigate the relationship between S-nitrosylation of spinal divalent metal transporter 1 (DMT1) modification and mechanism of remifentanil-induced hyperalgesia in rats.Methods:Forty pathogen-free healthy male Sprague-Dawley rats, aged 2-3 months, weighing 240-260 g, were divided into 4 groups ( n=10 each) using a random number table method: control group (group C), remifentanil group (group R), L-NAME group (group C+ L) and remifentanil+ L-NAME group (group R+ L). Normal saline was infused at a rate of 0.1 ml·kg -1·min -1 for 60 min via the caudal vein in C group. Remifentanil was infused at a rate of 1.0 μg·kg -1·min -1 for 60 min via the caudal vein in R group. L-NAME 30 mg/kg was intraperitoneally injected, and 10 min later normal saline was infused at a rate of 0.1 ml·kg -1·min -1 for 60 min in C+ L group. L-NAME 30 mg/kg was intraperitoneally injected, and 10 min later remifentanil was infused at a rate of 1.0 μg·kg -1·min -1 for 60 min in R+ L group. The mechanical paw withdrawal threshold (MWT) and thermal paw withdrawal latency (TWL) were measured at 24 h before iv infusion and 6, 24 and 48 h after the end of infusion (T 0-3). All the rats were sacrificed under anesthesia after the last measurement of pain thresholds, and the L 4-6 segments of the spinal cord were removed for determination of the expression of neuronal nitric oxide sythases (nNOS) and DMT1 mRNA (using quantitative real-time polymerase chain reaction), extraction of nitrosylated proteins (by biotin switch assay), expression of nNOS, total DMT1 and S-nitrosylation of DMT1 (by Western blot), nitric oxide (NO) content (by spectrophotometry) and iron content (using atomic absorption spectrophotometer). Results:Compared with group C, the MWT was significantly decreased, and the TWL was shortened at T 1-3 in group R ( P<0.05), and the expression of nNOS protein and mRNA and S-nitrosylation of DMT1 was significantly up-regulated, and contents of NO and iron were increased in R and R+ L groups ( P<0.05), and no significant change was found in each index in group C+ L ( P>0.05). Compared with group R, the MWT was significantly increased, and the TWL was prolonged at T 1-3, and the expression of nNOS protein and mRNA and S-nitrosylation of DMT1 was down-regulated, and contents of NO and iron were decreased in group R+ L ( P<0.05). Compared with group C+ L, the MWT was significantly decreased, and the TWL was shortened at T 1-3, and the expression of nNOS protein and mRNA and S-nitrosylation of DMT1 was up-regulated, and the contents of NO and iron were increased in group R+ L ( P<0.05). There were no significant differences in the expression of DMT1 mRNA and total DMT1 in spinal cord among all the groups ( P>0.05). Conclusions:Activation of nNOS induces an increase in NO generation in the spinal cord and mediates the S-nitrosylation of DMT1, which may be related to the mechanism of remifentanil-induced hyperalgesia in rats.

Chimeric antigen receptor T cell(CAR-T)immunotherapy is the most potential adoptive immunotherapy for malignant tumors,which needs no antigen presenting cells(APC)and is not limited by major histocompatibiliy complex(MHC). CAR-T immunotherapy not only recognizes and kills tumor cells directly,but also forms memory T cells and establishs long-term anti-tumor mechanism,of which the effect in leukemia,multiple myeloma and other non-solid tumors as well as the great potential in solid tumors have been widely verified. However,a variety of adverse reactions such as cytokine release syndrome(CRS),neurotoxicity(NT)and miss target effect are produced during CAR-T immunotherapy,of which the occurrence of CRS and NT may be related to the abnormal level of cytokines. Remarkable increase of cytokine level is a major characteristics of CRS. However,the increase of cytokines is neither the root cause nor the only result of CAR-T adverse reaction. CAR-T immunotherapy has a high incidence of adverse reaction which may even endanger the life of patients. Cytokine targeted drugs such as Anakinra and Tocilizumab may decrease the incidence of adverse reaction and improve the prognosis of patients. This paper reviews the correlation of cytokines with CRS and NT in CAR-T immunotherapy and the effect of cytokine targeting drugs,so as to provide a reference for the basic research,quality control and clinical application of CAR-T immunotherapy.

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 understand the status of uncertainty stress and occupational well-being of medical staff in Zhejiang Province, and to analysis the relationship between them, in the context of a pandemic of novel coronavirus pneumonia (corona virus disease 2019, COVID-19).Methods:From May to June 2021, 1 028 medical staff were selected from 8 Class Ⅲ hospitals in Zhejiang Province by convenience sampling. The cross-sectional survey was conducted with the General Information Questionnaire, the Uncertainty Stress Scale and the Occupational Well-being Scale. Pearson method was used to analyze the correlation between uncertain psychological stress and occupational well-being of medical staff, and multiple linear regression was used to analyze the influencing factors of occupational well-being of medical staff.Results:The total score of uncertainty stress of 1028 medical staff was (25.62±8.92), and the total score of occupational well-being was (75.03±14.68) at a moderate level, including 48 (4.7%) participants with a high level of occupational well-being. Uncertainty stress of medical staff was negatively correlated with occupational well-being ( r=-0.46, P<0.01). Multiple regression analysis showed that working years, hospital class, interests, leisure time, personality traits, status of self-reported health and levels of uncertainty stress had statistically significant influence on occupational well-being ( t=-2.30-10.28, all P<0.05). Conclusions:The occupational well-being of medical staff in Zhejiang Province needs to be improved. Health administrative departments should formulate targeted intervention measures to enhance the ability of medical staff to cope with uncertainty stress, so as to improve the occupational well-being of medical staff.

Objective:To compare oxytocin combined with ergometrine with oxytocin alone in terms of primary prophylaxis for postpartum hemorrhage (PPH) at the time of cesarean section (CS).Methods:This was a multicenter double-blind randomized controlled interventional study comparing ergometrine combined with oxytocin and oxytocin alone administered at CS. From December 2018 to November 2019, a total of 298 parturients were enrolled in 16 hospitals nationwide. They were randomly divided into experimental group (ergometrine intra-myometrial injection following oxytocin intravenously; 148 cases) and control group (oxytocin intra-myometrial injection following oxytocin intravenously; 150 cases) according to 1∶1 random allocation. The following indexes were compared between the two groups: (1) main index: blood loss 2 hours (h) after delivery; (2) secondary indicators: postpartum blood loss at 6 h and 24 h, placental retention time, incidence of PPH, the proportion of additional use of uterine contraction drugs, hemostatic drugs or other hemostatic measures at 2 h and 24 h after delivery, the proportion requiring blood transfusion, and the proportion of prolonged hospital stay due to poor uterine involution; (3) safety indicators: nausea, vomiting, dizziness and other adverse reactions, and blood pressure at each time point of administration.Results:(1) The blood loss at 2 h after delivery in the experimental group [(402±18) ml] was less than that in the control group [(505±18) ml], and the difference was statistically significant ( P<0.05). (2) The blood loss at 6 h and 24 h after delivery in the experimental group were less than those in the control group, and the differences were statistically significant (all P<0.05). There were no significant differences between the two groups in the incidence of PPH, the proportion of additional use of uterine contraction drugs, hemostatic drugs or other hemostatic measures at 2 h and 24 h after delivery, the proportion requiring blood transfusion, and the proportion of prolonged hospital stay due to poor uterine involution (all P>0.05). (3) Adverse reactions occurred in 2 cases (1.4%, 2/148) in the experimental group and 1 case (0.7%, 1/150) in the control group. There was no significant difference between the two groups ( P>0.05). The systolic blood pressure within 2.0 h and diastolic blood pressure within 1.5 h of drug administration in the experimental group were higher than those in the control group, and the differences were statistically significant ( P<0.05), but the blood pressure of the two groups were in the normal range. Conclusion:The use of ergometrine injection in CS could reduce the amount of PPH, which is safe and feasible.

Objective:To evaluate the optimization efficacy of transversus thoracic muscle plane block (TTPB)-pectoral nerve block (PECS) with compound lidocaine-general anesthesia for modified radical mastectomy for breast cancer.Methods:Ninety female patients, aged 40-64 yr, with American Society of Anesthesiologists physical status Ⅰ or Ⅱ and body mass index <30 kg/m 2, undergoing elective modified radical mastectomy for breast cancer, were divided into 3 groups ( n=30 each) using the random number table method: general anesthesia group (group C), TTPB-PECS with compound lidocaine-general anesthesia group (group L), and TTPB-PECS with ropivacaine-general anesthesia group (group R). The laryngeal mask was used for total intravenous anesthesia.PECS I, PECS II and TTPB were performed sequentially after laryngeal mask placement in L and R groups, and 0.4% compound lidocaine 15, 15 and 10 ml (group L) and 0.375% ropivacaine 15, 15 and 10 ml (group R) were injected at the above three points, respectively.Patient-controlled intravenous analgesia (PCIA) was performed with sufentanil at patient-controlled analgesia (PCA) dose of 2 ml/dose and a lockout time of 15 min at the end of operation, and when visual analog scale (VAS) score ≥ 3 points, sufentanil 5 μg was given intravenously for rescue analgesia.The intraoperative consumption of propofol and remifentanil, emergence time, and laryngeal mask removal time were recorded.The Ramsay sedation score and duration of postoperative analgesia were recorded at 10 min after removal of the laryngeal mask.The consumption of sufentanil, ratio of the effective pressing times to the total pressing times of PCA (D 1/D 2 ratio), requirement for rescue analgesia, and occurrence of adverse effects such as nausea and vomiting, skin pruritus, bradycardia, and respiratory depression within 48 h after surgery were recorded. Results:Compared with C group, the intraoperative consumption of propofol and remifentanil was significantly reduced, the emergence time and laryngeal mask removal time were shortened, Ramsay sedation scores was decreased, postoperative VAS scores were decreased, duration of postoperative analgesia was prolonged, D 1/D 2 ratios were increased, the consumption of sufentanil was reduced, and the requirement for rescue analgesia and incidence of postoperative nausea and vomiting were decreased in R and L groups ( P<0.05). Compared with R group, the duration of postoperative analgesia was significantly prolonged, D 1/D 2 ratio was increased, the consumption of sufentanil was decreased, and the requirement for rescue analgesia was decreased in L group ( P<0.05). Conclusions:Compared with general anesthesia, TTPB-PECS with compound lidocaine-general anesthesia used in modified radical mastectomy for breast cancer is helpful in achieving a low-opioid anesthetic mode, which is more conducive to suppressing postoperative hyperalgesia and promoting early postoperative recovery, and the optimization efficacy is more significant than that of ropivacaine.