BACKGROUND:Macrophage migration inhibitory factor(MIF)is a pleiotropic cytokine,which is secreted in different types of stem cells and can regulate the proliferation,differentiation and migration of various types of stem cells.Our previous research has confirmed that human embryonic stem cells secrete MIF and that its concentration in the culture medium is relatively stable.However,whether MIF is involved in the survival,proliferation and differentiation of human embryonic stem cells remains unclear. OBJECTIVE:To investigate the effects of MIF on survival,proliferation,and differentiation of human embryonic stem cells. METHODS:(1)Human embryonic stem cells H9 were cultured.The growth curve of cells was detected and plotted by CCK-8 assay.Enzyme-linked immunosorbent assay was used to determine the level of MIF in the medium.(2)To determine the effects of exogenous MIF on the survival and proliferation of human embryonic stem cells,different groups were established:the control group,which was cultured in stem cell medium without any modifications;the exogenous MIF group,which was treated with different concentrations(30,100,300 ng/mL)of MIF in the stem cell medium;the MIF inhibitor ISO-1 group,which was treated with different concentrations(2,7,21 μmol/L)of ISO-1 in the stem cell medium;and the MIF+ISO-1 group,which was treated with different concentrations of ISO-1 along with 100 ng/mL of MIF.Cell viability was assessed using the CCK-8 assay.(3)To further elucidate the effect of MIF gene on survival and proliferation of human embryonic stem cell,the MIF knockout H9 cell line was constructed by CRISPR-Cas 9 technology to observe the lineage establishment.(4)To determine the effect of high concentrations of MIF on human embryonic stem cell differentiation,100 ng/mL MIF and 100 ng/mL of CXCR4 neutralizing antibody were separately added to the normal stem cell culture medium.The expression levels of self-renewal factors(KLF4,c-MYC,NANOG,OCT4,and SOX2)and differentiation transcription factors(FOXA2,OTX2)were measured using real-time quantitative polymerase chain reaction,immunofluorescence staining,and western blot analysis. RESULTS AND CONCLUSION:(1)The logarithmic growth phase of H9 cells was between 3-6 days.Under normal growth conditions,human embryonic stem cells secreted MIF at a concentration of approximately 20 ng/mL,independent of cell quantity.(2)Compared to the control group,the addition of different concentrations of MIF had no effect on the proliferation of human embryonic stem cells(P>0.05).ISO-1 significantly inhibited the proliferation of human embryonic stem cells,with a stronger inhibition observed at higher concentrations of ISO-1(P<0.05).The addition of MIF in the presence of ISO-1 reduced the inhibitory effect of ISO-1(P<0.05).(3)Real-time quantitative polymerase chain reaction showed that knocking out 50%of the MIF gene resulted in a significant decrease in the growth vitality of human embryonic stem cells and failure to establish cell lines.(4)Adding 100 ng/mL exogenous MIF to the culture medium resulted in a decrease in the mRNA,protein,and fluorescence expression levels of the self-renewal transcription factor KLF4,while the mRNA,protein,and fluorescence expression levels of the differentiation factor FOXA2 increased.(5)When 100 ng/mL CXCR4 neutralizing antibody was added to the culture medium,the mRNA and protein expression levels of KLF4 increased,while the mRNA and protein expression levels of FOXA2 decreased,contrary to the expression trend observed in the MIF group.In conclusion,the endogenous secretion of MIF by human embryonic stem cells is essential for their survival.The addition of MIF to the culture medium does not promote the proliferation of human embryonic stem cells.However,it can lead to a decrease in the expression of the self-renewal factor KLF4 and an increase in the expression of the transcription factor FOXA2.This provides a clue for further investigation into the effects and mechanisms of MIF on the differentiation of human embryonic stem cells.The MIF-CXCR4 axis plays a regulatory role in this process.

Background: The transvenous approach to the treatment of cerebral arteriovenous malformation (AVM) is difficult and requires strict blood pressure and blood flow control; however, the cure rate is very high. Appropriate blood pressure control techniques can greatly benefit these patients.Case: A 55-year-old male patient was found to have an aneurysm complicated with a cerebral AVM (length: 2.0 cm, width: 1.6 cm, height: 1.2 cm). Aneurysm embolization was considered for the first-stage surgery and transvenous AVM embolization for the second-stage surgery. Rapid ventricular pacing (RVP) provided a stable blood flow environment for the surgery, which was completed successfully. Conclusion RVP can thus provide an ideal condition for the embolization of cerebral AVM through the transvenous approach and can be a viable surgical option.

Background: The transvenous approach to the treatment of cerebral arteriovenous malformation (AVM) is difficult and requires strict blood pressure and blood flow control; however, the cure rate is very high. Appropriate blood pressure control techniques can greatly benefit these patients.Case: A 55-year-old male patient was found to have an aneurysm complicated with a cerebral AVM (length: 2.0 cm, width: 1.6 cm, height: 1.2 cm). Aneurysm embolization was considered for the first-stage surgery and transvenous AVM embolization for the second-stage surgery. Rapid ventricular pacing (RVP) provided a stable blood flow environment for the surgery, which was completed successfully. Conclusion RVP can thus provide an ideal condition for the embolization of cerebral AVM through the transvenous approach and can be a viable surgical option.

Background: The transvenous approach to the treatment of cerebral arteriovenous malformation (AVM) is difficult and requires strict blood pressure and blood flow control; however, the cure rate is very high. Appropriate blood pressure control techniques can greatly benefit these patients.Case: A 55-year-old male patient was found to have an aneurysm complicated with a cerebral AVM (length: 2.0 cm, width: 1.6 cm, height: 1.2 cm). Aneurysm embolization was considered for the first-stage surgery and transvenous AVM embolization for the second-stage surgery. Rapid ventricular pacing (RVP) provided a stable blood flow environment for the surgery, which was completed successfully. Conclusion RVP can thus provide an ideal condition for the embolization of cerebral AVM through the transvenous approach and can be a viable surgical option.

Background: The transvenous approach to the treatment of cerebral arteriovenous malformation (AVM) is difficult and requires strict blood pressure and blood flow control; however, the cure rate is very high. Appropriate blood pressure control techniques can greatly benefit these patients.Case: A 55-year-old male patient was found to have an aneurysm complicated with a cerebral AVM (length: 2.0 cm, width: 1.6 cm, height: 1.2 cm). Aneurysm embolization was considered for the first-stage surgery and transvenous AVM embolization for the second-stage surgery. Rapid ventricular pacing (RVP) provided a stable blood flow environment for the surgery, which was completed successfully. Conclusion RVP can thus provide an ideal condition for the embolization of cerebral AVM through the transvenous approach and can be a viable surgical option.

Objective: To investigate the positive rate of drug-induced antibodies produced by the clinical application of β-lactam antibiotics, and analyze the differences in the detection methods and related influencing factors. Methods: A total of 350 adult inpatients who developed anemia after using β-lactam antibiotics for 3 days or more in Inner Mongolia People's hospital were selected as the experimental group, and 240 adult inpatients treated with β-lactam antibiotics for 3 days or more who did not develop anemia as the control group. The drug-induced antibody tests, direct antiglobulin tests, and unexpected antibody screening were performed on both groups, and the influencing factors of drug-induced antibodies were analyzed. Results: The numbers of positive cases of drug-induced antibody detected by the drug-coated red blood cell method in the experimental group and the control group were 12(12/350, 3.43%) and 2(2/240, 0.83%) respectively, with statistically significant differences (P<0.05). No drug-induced antibodies were detected in either group using the drug addition method. In the experimental group, the red blood cell method detected β-lactam drug-induced antibodies in 12 cases (12/350, 3.43%), while the drug added method detected 0 cases (0/350, 0.00%), with statistically significant differences (P<0.05). In the control group, the detection rates of two methods showed no statistically significant difference (P>0.05). In the experimental group, 7 cases of β-lactam antibodies were detected in the cephalosporin group (7/293, 2.40%) and 5 cases in the non-cephalosporin group (5/58, 8.62%), with statistically significant differences (P<0.05). There was no statistically significant difference between the second-generation and third-generation cephalosporin drugs (P>0.05). When the experimental group was stratified according to the history of blood transfusion and the blood type of patients, no statistically significant differences were observed between subgroups (P>0.05). Conclusion: Anemia may be related to the production of drug-induced antibodies followingβ-lactam antibiotics treatment. Therefore, improving the clinical awareness of drug-induced antibodies to β-lactam antibiotics is of great significance to clarify the causes of anemia and reduce unnecessary blood transfusions.

Objective: To investigate the positive rate of drug-induced antibodies produced by the clinical application of β-lactam antibiotics, and analyze the differences in the detection methods and related influencing factors. Methods: A total of 350 adult inpatients who developed anemia after using β-lactam antibiotics for 3 days or more in Inner Mongolia People's hospital were selected as the experimental group, and 240 adult inpatients treated with β-lactam antibiotics for 3 days or more who did not develop anemia as the control group. The drug-induced antibody tests, direct antiglobulin tests, and unexpected antibody screening were performed on both groups, and the influencing factors of drug-induced antibodies were analyzed. Results: The numbers of positive cases of drug-induced antibody detected by the drug-coated red blood cell method in the experimental group and the control group were 12(12/350, 3.43%) and 2(2/240, 0.83%) respectively, with statistically significant differences (P<0.05). No drug-induced antibodies were detected in either group using the drug addition method. In the experimental group, the red blood cell method detected β-lactam drug-induced antibodies in 12 cases (12/350, 3.43%), while the drug added method detected 0 cases (0/350, 0.00%), with statistically significant differences (P<0.05). In the control group, the detection rates of two methods showed no statistically significant difference (P>0.05). In the experimental group, 7 cases of β-lactam antibodies were detected in the cephalosporin group (7/293, 2.40%) and 5 cases in the non-cephalosporin group (5/58, 8.62%), with statistically significant differences (P<0.05). There was no statistically significant difference between the second-generation and third-generation cephalosporin drugs (P>0.05). When the experimental group was stratified according to the history of blood transfusion and the blood type of patients, no statistically significant differences were observed between subgroups (P>0.05). Conclusion: Anemia may be related to the production of drug-induced antibodies followingβ-lactam antibiotics treatment. Therefore, improving the clinical awareness of drug-induced antibodies to β-lactam antibiotics is of great significance to clarify the causes of anemia and reduce unnecessary blood transfusions.

Objectives To explore the feasibility of temporary veno-venous extracorporeal membrane oxygenation(VV-ECMO)technology for early on-site treatment,through establishing an animal model of severe blast lung injury in goats by free-field chemical explosion experiments in high-altitude regions.Methods A total of 16 adult goats were selected,and divided into the control group and the treatment group according to the random number table method,with 8 goats in each group.A model of severe blast lung injury was established at an altitude of 4 600 meters above sea level,then the goats in the control group were given respiratory support and the goats in the treatment group were given temporary VV-ECMO treatment.The survival status of the goats 15 minutes after injury was recorded,the vital signs[including body temperature,respiration rate,heart rate,and mean arterial pressure(MAP)]and arterial blood gas analysis indicators[including pH,arterial partial pressure of oxygen(PO2),arterial partial pressure of carbon dioxide(PCO2),oxygen saturation(SaO2),lactate(LAC),calcium(Ca2+),hematocrit(HCT),and hemoglobin(Hb)]before injury and 1 hour,2 hours,3 hours after injury were compared in the two groups.The post-mortem examination was performed on all dead goats and sacrificed goats after treatment,the severity of lung injury was assessed by organ injury scaling(OIS),and the lung injury score was evaluated by abbreviated injury scale(AIS).The wet-to-dry weight ratio(W/D)and lung coefficient were calculated.Results Within 15 minutes after the explosion,4 goats in the control group died and 4 goats survived;and 5 goats in the treatment group died and 3 goats survived.There was no statistically significant difference in the body temperature,respiration rate,heart rate,or MAP before and after injury between the two groups(P>0.05).The PaO2 and SaO2 1 hour,2 hours,and 3 hours after injury in the treatment group were superior than those in the control group(P<0.05),the Ca2+ 2 hours after injury was significantly higher than that in the control group(P<0.05),and there was no statistically significant difference in the pH,PCO2,LAC,HCT or Hb at different time points after injury between the two groups(P>0.05).There was no statistically significant difference in the OIS,AIS or lung coefficient between the two groups(P>0.05),but the W/D of the lung tissue in the control group was lower than that in the treatment group(P<0.05).Conclusion We have established a novel,feasible,and stable treatment effect temporary VV-ECMO animal treatment strategy for the first time in the high-altitude regions,which can provide animal experiment evidence for the early on-site VV-ECMO treatment of severe blast lung injury in high-altitude regions.

Objective To investigate the distribution and antimicrobial resistance profiles of the common pathogens isolated from urine from 2015 to 2021 in the CHINET Antimicrobial Resistance Surveillance Program.Methods The bacterial strains were isolated from urine and identified routinely in 51 hospitals across China in the CHINET Antimicrobial Resistance Surveillance Program from 2015 to 2021.Antimicrobial susceptibility was determined by Kirby-Bauer method,automatic microbiological analysis system and E-test according to the unified protocol.Results A total of 261 893 nonduplicate strains were isolated from urine specimen from 2015 to 2021,of which gram-positive bacteria accounted for 23.8％(62 219/261 893),and gram-negative bacteria 76.2％(199 674/261 893).The most common species were E.coli(46.7％),E.faecium(10.4％),K.pneumoniae(9.8％),E.faecalis(8.7％),P.mirabilis(3.5％),P.aeruginosa(3.4％),SS.agalactiae(2.6％),and E.cloacae(2.1％).The strains were more frequently isolated from inpatients versus outpatients and emergency patients,from females versus males,and from adults versus children.The prevalence of ESBLs-producing strains in E.coli,K.pneumoniae and P.mirabilis was 53.2％,52.8％and 37.0％,respectively.The prevalence of carbapenem-resistant strains in E.coli,K.pneumoniae,P.aeruginosa and A.baumannii was 1.7％,18.5％,16.4％,and 40.3％,respectively.Lower than 10％of the E.faecalis isolates were resistant to ampicillin,nitrofurantoin,linezolid,vancomycin,teicoplanin and fosfomycin.More than 90％of the E.faecium isolates were ressitant to ampicillin,levofloxacin and erythromycin.The percentage of strains resistant to vancomycin,linezolid or teicoplanin was＜2％.The E.coli,K.pneumoniae,P.aeruginosa and A.baumannii strains isolated from ICU inpatients showed significantly higher resistance rates than the corresponding strains isolated from outpatients and non-ICU inpatients.Conclusions E.coli,Enterococcus and K.pneumoniae are the most common pathogens in urinary tract infection.The bacterial species and antimicrobial resistance of urinary isolates vary with different populations.More attention should be paid to antimicrobial resistance surveillance and reduce the irrational use of antimicrobial agents.

Objective To understand the distribution and changing resistance profiles of clinical isolates of Enterococcus in hospitals across China from 2015 to 2021.Methods Antimicrobial susceptibility testing was conducted for the clinical isolates of Enterococcus according to the unified protocol of CHINET program by automated systems,Kirby-Bauer method,or E-test strip.The results were interpreted according to the Clinical & Laboratory Standards Institute(CLSI)breakpoints in 2021.WHONET 5.6 software was used for statistical analysis.Results A total of 124 565 strains of Enterococcus were isolated during the 7-year period,mainly including Enterococcus faecalis(50.7％)and Enterococcus faecalis(41.5％).The strains were mainly isolated from urinary tract specimens(46.9％±2.6％),and primarily from the patients in the department of internal medicine,surgery and ICU.E.faecium and E.faecalis strains showed low level resistance rate to vancomycin,teicoplanin and linezolid(≤3.6％).The prevalence of vancomycin-resistant E.faecalis and E.faecium was 0.1％and 1.3％,respectively.The prevalence of linezolid-resistant E.faecalis increased from 0.7％in 2015 to 3.4％in 2021,while the prevalence of linezolid-resistant E.faecium was 0.3％.Conclusions The clinical isolates of Enterococcus were still highly susceptible to vancomycin,teicoplanin,and linezolid,evidenced by a low resistance rate.However,the prevalence of linezolid-resistant E.faecalis was increasing during the 7-year period.It is necessary to strengthen antimicrobial resistance surveillance to effectively identify the emergence of antibiotic-resistant bacteria and curb the spread of resistant pathogens.