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.

A domestically produced self-expanding transcatheter aortic valve controllable bending delivery system(VitaFlow? Ⅲcontrollable bending retrievable delivery system)was first used to perform transcatheter aortic valve replacement(TAVR)in a symptomatic severe aortic valve stenosis patient with severe heart failure and high risk of surgery in China on September 22,2023.The patient successfully completed TAVR under general anesthesia,with good valve position and function after the operation.Before discharge and at one month of follow-up,the patient's symptoms and degree of heart failure were significantly improved.The follow-up results of this case showed that the VitaFlow? Ⅲ controllable bending retrievable delivery system for TAVR is safe and feasible,and future prospective,multicenter clinical trials are expected to evaluate its efficacy.

The aqueous two-phase system (ATPS) is an all-aqueous system fabricated from two immiscible aqueous phases. It is spontaneously assembled through physical liquid-liquid phase separation (LLPS) and can create suitable templates like the multicompartment of the intracellular environment. Delicate structures containing multiple compartments make it possible to endow materials with advanced functions. Due to the properties of ATPSs, ATPS-based drug delivery systems exhibit excellent biocompatibility, extraordinary loading efficiency, and intelligently controlled content release, which are particularly advantageous for delivering drugs in vivo. Therefore, we will systematically review and evaluate ATPSs as an ideal drug delivery system. Based on the basic mechanisms and influencing factors in forming ATPSs, the transformation of ATPSs into valuable biomaterials is described. Afterward, we concentrate on the most recent cutting-edge research on ATPS-based delivery systems. Finally, the potential for further collaborations between ATPS-based drug-carrying biomaterials and disease diagnosis and treatment is also explored.

OBJECTIVE To conduct rapid health technology assessment （HTA） of ulinastatin （UTI）， and to evaluate the efficacy， safety and cost-effectiveness of UTI in the treatment of acute pancreatitis （AP）. METHODS Retrieved from PubMed， Embase， the Cochrane Library， CNKI， Wanfang database， CBM and official websites of HTA institutions， the systematic review （SR）/meta-analysis， economic evaluation and HTA reports of UTI in the treatment of AP were collected from the inception to Apr. 2024. Two researchers independently conducted screening， quality evaluation and data extraction according to the admission and exclusion criteria， and descriptive analysis was adopted to analyze and summarize the data. RESULTS A total of 19 studies were included， involving 15 SR/meta-analysis and 4 economic studies， and no HTA report was retrieved. In the treatment of AP， UTI showed clear advantages over conventional treatment alone in terms of improving the overall effective rate， shortening the recovery time of amylase， reducing the time required to relieve abdominal pain and distension， lowering the mortality rate， and decreasing the average hospital stay. Compared to other positive drugs （carbendate mesylate， octreotide， somatostatin， etc.）， its efficacy is similar， with a favorable safety profile. As far as the current research was concerned， UTI had obvious economic advantages over other positive drugs. CONCLUSIONS UTI is safe and effective in the treatment of AP， and has economic advantages.