Objective The aim of this study was to investigate the effect of p38 on stem cell maintenance of pancreatic cancer. Methods Human pancreatic cancer cells PANC-1 were treated with different concentrations of 5-fluorouracil(5-FU)(0.5×IC₅₀, IC₅₀, and 2×IC₅₀) for 24 hours, and VX-702 (p38 phosphorylation inhibitor) was added, and the cells were inoculated in 6-well culture dishes with ultra-low adhesion to observe the changes of sphere tumors. The expression levels of cyclin-dependent kinase 2(CDK2), cyclin B1 and D1, Octamer-binding transcription factor 4(OCT4), SRY-box transcription factor 2(SOX2), Nanog and p38 were measured by Western blot. The mRNA expression levels of p38, OCT4, Nanog and SOX2 were tested by RT-PCR. Cell cycle, apoptosis, and the proportion of CD44⁺CD133⁺PANC-1 cells were evaluated by flow cytometry. Results The results showed that 5-FU inhibited the formation of tumor spheres in PANC-1 cells, increased CD44⁺CD133⁺cell fragments, down-regulated the expression of OCT4, Nanog and SOX2, and inhibited the stemness maintenance of PANC-1 tumor stem cells. Phosphorylation of PANC-1 cells was inhibited by a highly selective p38 MAPK inhibitor, VX-702(p38 mitogen-activated protein kinase inhibitor), which had the same effect as 5-FU treatment. When VX-702 combined with 5-FU was used to treat PANC-1 cells, the therapeutic effect was enhanced. Conclusion p38 inhibitors decreased PANC-1 cell activity and increased cell apoptosis. p38 inhibitors inhibit the stemness maintenance of pancreatic cancer stem cells.
Humans ; Phosphorylation/drug effects* ; Cell Line, Tumor ; p38 Mitogen-Activated Protein Kinases/antagonists & inhibitors* ; Neoplastic Stem Cells/metabolism* ; Drug Resistance, Neoplasm/drug effects* ; Fluorouracil/pharmacology* ; Pancreatic Neoplasms/pathology* ; Apoptosis/drug effects* ; SOXB1 Transcription Factors/genetics* ; Octamer Transcription Factor-3/genetics*

To investigate the clinical value of cardiac magnetic resonance feature tracking (CMR-FT) technology in the assessment of the right ventricle function in patients with immune checkpoint inhibitor (ICIs)-related myocarditis.

Purpose To compare the 5.0T gradient echo coronary magnetic resonance angiography(CMRA)using compressed sensing(CS)acceleration technology(5.0TCS-CMRA)vs.3.0T gradient echo-CMRA(3.0TCS-CMRA)using CS.Materials and Methods Twenty-five healthy volunteers aged 23 to 30 years from December 16,2023 to January 14,2024 at Peking Union Medical College Hospital,Chinese Academy of Medical Sciences were prospective enrolled in this study.The interval between 3.0TCS-CMRA and 5.0TCS-CMRA was within two weeks.3.0TCS-CMRA used T2 preparation and 5.0TCS-CMRA did not use T2 preparation.The image quality scores,coronary artery length,signal-to-noise ratio(SNR)and contrast-to-noise ratio between coronary blood and adjacent myocardium or tissue(CNRmyo-blood)were evaluated.Results On 5.0TCS-CMRA,the SNR and CNRmyo-blood of the proximal right coronary artery(RCA)in 25 healthy volunteers were significantly higher than those of 3.0TCS-CMRA(SNR:318.07±94.06 vs.223.81±51.19,t=-5.609,P<0.001;CNRmyo-blood:212.75±91.44 vs.149.70±59.53,Z=-3.619,P<0.001),while the SNR and CNRmyo-blood of proximal left anterior descending coronary artery(LAD)and left circumflex coronary artery(LCX)were not significantly higher than those of 3.0TCS-CMRA(SNR:315.52±102.49 vs.306.35±92.85,t=-0.627,P=0.536;289.72±88.79 vs.272.87±84.68,t=-1.226,P=0.232;CNRmyo-blood:135.83±93.53 vs.203.94±74.30,t=4.132,P<0.001;117.66±79.63 vs.161.60±78.91,t=3.127,P=0.005).The length of the three coronary arteries measured by 5.0TCS-CMRA was significantly shorter than that of 3.0TCS-CMRA[RCA:(126.04±31.54)mm vs.(137.20±29.93)mm,t=2.911,P=0.008;LAD:(122.68±24.63)mm vs.(134.24±23.38)mm,Z=-3.026,P=0.002;LCX:(57.07±26.70)mm vs.(68.27±24.02)mm,t=2.552,P=0.018].There was no significant difference in the scanning time required between 3.0TCS-CMRA and 5.0TCS-CMRA[(8.60±2.84)min vs.(8.30±2.32)min,Z=-0.183,P=0.855].The image scores of the three major coronary arteries of 5.0TCS-CMRA were significantly lower than those of 3.0TCS-CMRA(RCA:2.52±0.59 vs.3.16±0.69,Z=-3.258,P=0.001;LAD:2.72±0.74 vs.3.24±0.66,Z=-2.540,P=0.011;LCX:2.44±0.71 vs.3.00±0.87,Z=-2.462,P=0.014).Conclusion In the absence of T2 preparation,5.0TCS-CMRA can still show obvious advantages in the SNR and CNRmyo-blood of proximal RCA compared with 3.0TCS-CMRA,which suggests the application potential of 5.0TCS-CMRA.In the future,a suitable T2 preparation pulse or potential alternative may significantly improve the performance of the 5.0TCS-CMRA.

Purpose To compare the 5.0T gradient echo coronary magnetic resonance angiography(CMRA)using compressed sensing(CS)acceleration technology(5.0TCS-CMRA)vs.3.0T gradient echo-CMRA(3.0TCS-CMRA)using CS.Materials and Methods Twenty-five healthy volunteers aged 23 to 30 years from December 16,2023 to January 14,2024 at Peking Union Medical College Hospital,Chinese Academy of Medical Sciences were prospective enrolled in this study.The interval between 3.0TCS-CMRA and 5.0TCS-CMRA was within two weeks.3.0TCS-CMRA used T2 preparation and 5.0TCS-CMRA did not use T2 preparation.The image quality scores,coronary artery length,signal-to-noise ratio(SNR)and contrast-to-noise ratio between coronary blood and adjacent myocardium or tissue(CNRmyo-blood)were evaluated.Results On 5.0TCS-CMRA,the SNR and CNRmyo-blood of the proximal right coronary artery(RCA)in 25 healthy volunteers were significantly higher than those of 3.0TCS-CMRA(SNR:318.07±94.06 vs.223.81±51.19,t=-5.609,P<0.001;CNRmyo-blood:212.75±91.44 vs.149.70±59.53,Z=-3.619,P<0.001),while the SNR and CNRmyo-blood of proximal left anterior descending coronary artery(LAD)and left circumflex coronary artery(LCX)were not significantly higher than those of 3.0TCS-CMRA(SNR:315.52±102.49 vs.306.35±92.85,t=-0.627,P=0.536;289.72±88.79 vs.272.87±84.68,t=-1.226,P=0.232;CNRmyo-blood:135.83±93.53 vs.203.94±74.30,t=4.132,P<0.001;117.66±79.63 vs.161.60±78.91,t=3.127,P=0.005).The length of the three coronary arteries measured by 5.0TCS-CMRA was significantly shorter than that of 3.0TCS-CMRA[RCA:(126.04±31.54)mm vs.(137.20±29.93)mm,t=2.911,P=0.008;LAD:(122.68±24.63)mm vs.(134.24±23.38)mm,Z=-3.026,P=0.002;LCX:(57.07±26.70)mm vs.(68.27±24.02)mm,t=2.552,P=0.018].There was no significant difference in the scanning time required between 3.0TCS-CMRA and 5.0TCS-CMRA[(8.60±2.84)min vs.(8.30±2.32)min,Z=-0.183,P=0.855].The image scores of the three major coronary arteries of 5.0TCS-CMRA were significantly lower than those of 3.0TCS-CMRA(RCA:2.52±0.59 vs.3.16±0.69,Z=-3.258,P=0.001;LAD:2.72±0.74 vs.3.24±0.66,Z=-2.540,P=0.011;LCX:2.44±0.71 vs.3.00±0.87,Z=-2.462,P=0.014).Conclusion In the absence of T2 preparation,5.0TCS-CMRA can still show obvious advantages in the SNR and CNRmyo-blood of proximal RCA compared with 3.0TCS-CMRA,which suggests the application potential of 5.0TCS-CMRA.In the future,a suitable T2 preparation pulse or potential alternative may significantly improve the performance of the 5.0TCS-CMRA.

Objective To monitor the susceptibility of clinical isolates to antimicrobial agents in tertiary hospitals in major regions of China in 2022.Methods Clinical isolates from 58 hospitals in China were tested for antimicrobial susceptibility using a unified protocol based on disc diffusion method or automated testing systems.Results were interpreted using the 2022 Clinical &Laboratory Standards Institute(CLSI)breakpoints.Results A total of 318 013 clinical isolates were collected from January 1,2022 to December 31,2022,of which 29.5％were gram-positive and 70.5％were gram-negative.The prevalence of methicillin-resistant strains in Staphylococcus aureus,Staphylococcus epidermidis and other coagulase-negative Staphylococcus species(excluding Staphylococcus pseudintermedius and Staphylococcus schleiferi)was 28.3％,76.7％and 77.9％,respectively.Overall,94.0％of MRSA strains were susceptible to trimethoprim-sulfamethoxazole and 90.8％of MRSE strains were susceptible to rifampicin.No vancomycin-resistant strains were found.Enterococcus faecalis showed significantly lower resistance rates to most antimicrobial agents tested than Enterococcus faecium.A few vancomycin-resistant strains were identified in both E.faecalis and E.faecium.The prevalence of penicillin-susceptible Streptococcus pneumoniae was 94.2％in the isolates from children and 95.7％in the isolates from adults.The resistance rate to carbapenems was lower than 13.1％in most Enterobacterales species except for Klebsiella,21.7％-23.1％of which were resistant to carbapenems.Most Enterobacterales isolates were highly susceptible to tigecycline,colistin and polymyxin B,with resistance rates ranging from 0.1％to 13.3％.The prevalence of meropenem-resistant strains decreased from 23.5％in 2019 to 18.0％in 2022 in Pseudomonas aeruginosa,and decreased from 79.0％in 2019 to 72.5％in 2022 in Acinetobacter baumannii.Conclusions The resistance of clinical isolates to the commonly used antimicrobial agents is still increasing in tertiary hospitals.However,the prevalence of important carbapenem-resistant organisms such as carbapenem-resistant K.pneumoniae,P.aeruginosa,and A.baumannii showed a downward trend in recent years.This finding suggests that the strategy of combining antimicrobial resistance surveillance with multidisciplinary concerted action works well in curbing the spread of resistant bacteria.

Objective To evaluate the diagnostic value of myocardial work related parameters in coronary ischemia patients with coronary artery disease(CAD)coronary ischemia using non-invasive left ventricular pressure strain loop(PSL),taking fraction flow reservation(FFR)as the gold standard.Methods From December 2020 to December 2021,53 clinically suspected CAD patients were prospectively enrolled.All patients underwent echocardiography,invasive coronary angiography and FFR measurement.According to the results of coronary angiography,patients were divided into myocardial ischemia group(n=24,FFR≤0.80)and non-myocardial ischemia group(n=29,FFR＞0.80).PSL was used for off-line analysis to obtain the global work index(GWI),global constructive work(GCW),global wasted work(GWW),global work efficiency(GWE),global positive work(GPW),and global systolic constructive work(GSCW)and other myocardial work parameters.The differences of parameter values between the two groups were compared.The diagnostic efficacy of work parameters in myocardial ischemia was analyzed by ROC curve.Results Compared with the non-myocardial ischemia group,GWI,GCW,GPW and GSCW were significantly decreased in the myocardial ischemia group at the 18-,16-,and 12-segment levels(P＜0.001).The ROC curve showed that the AUC results of GWI,GCW,GPW,GSCW at the 18-segment level were 0.803(95％CI 0.679-0.927),0.807(95％CI 0.687-0.928),0.822(95％CI 0.708-0.936),0.819(95％CI 0.703-0.935).The optimal cut-off value of GWI was 1 676.3 mmHg％,and the sensitivity,specificity and accuracy of predicting myocardial ischemia were 70.8％,86.2％and 79.2％,respectively.The optimal cut-off value of GCW was 1 999.4 mmHg％,and the sensitivity,specificity and accuracy of predicting myocardial ischemia were 75.0％,82.8％and 79.2％,respectively.Conclusions Analyzing myocardial work using PSL has good significance for screening suspected myocardial ischemia in CAD patients.

Objective To monitor the susceptibility of clinical isolates to antimicrobial agents in healthcare facilities in major regions of China in 2023.Methods Clinical isolates collected from 73 hospitals across China were tested for antimicrobial susceptibility using a unified protocol based on disc diffusion method or automated testing systems.Results were interpreted using the 2023 Clinical & Laboratory Standards Institute (CLSI) breakpoints.Results A total of 445199 clinical isolates were collected in 2023,of which 29.0％ were gram-positive and 71.0％ were gram-negative.The prevalence of methicillin-resistant strains in Staphylococcus aureus,Staphylococcus epidermidis and other coagulase-negative Staphylococcus species (excluding Staphylococcus pseudintermedius and Staphylococcus schleiferi) (MRSA,MRSE and MRCNS) was 29.6％,81.9％ and 78.5％,respectively.Methicillin-resistant strains showed significantly higher resistance rates to most antimicrobial agents than methicillin-susceptible strains (MSSA,MSSE and MSCNS).Overall,92.9％ of MRSA strains were susceptible to trimethoprim-sulfamethoxazole and 91.4％ of MRSE strains were susceptible to rifampicin.No vancomycin-resistant strains were found.Enterococcus faecalis had significantly lower resistance rates to most antimicrobial agents tested than Enterococcus faecium.A few vancomycin-resistant strains were identified in both E.faecalis and E.faecium.The prevalence of penicillin-susceptible Streptococcus pneumoniae was 93.1％ in the isolates from children and and 95.9％ in the isolates from adults.The resistance rate to carbapenems was lower than 15.0％ for most Enterobacterales species except for Klebsiella,22.5％ and 23.6％ of which were resistant to imipenem and meropenem,respectively .Most Enterobacterales isolates were highly susceptible to tigecycline,colistin and polymyxin B,with resistance rates ranging from 0.6％ to 10.0％.The resistance rate to imipenem and meropenem was 21.9％ and 17.4％ for Pseudomonas aeruginosa,respectively,and 67.5％ and 68.1％ for Acinetobacter baumannii,respectively.Conclusions Increasing resistance to the commonly used antimicrobial agents is still observed in clinical bacterial isolates.However,the prevalence of important crabapenem-resistant organisms such as crabapenem-resistant K.pneumoniae,P.aeruginosa,and A.baumannii showed a slightly decreasing trend.This finding suggests that strengthening bacterial resistance surveillance and multidisciplinary linkage are important for preventing the occurrence and development of bacterial resistance.

Injury biomechanics is an interdisciplinary field that studies the biomechanical responses and injury mechanisms of the human body under external loads.The goal is to provide scientific foundations for the prevention,diagnosis,and treatment of human injuries.This field is widely applied in clinical medicine,sports science,rehabilitation engineering,traffic safety,aerospace,and other domains.In this review,the research progress in injury biomechanics in the year 2023 is summarized,focusing on in-depth analysis of injury mechanisms,innovations in injury prediction and protective countermeasure,and the latest applications of injury diagnosis and rehabilitation technologies.By systematically reviewing the research advancements,this review aims to offer new directions and ideas to the continued development of injury biomechanics and promote interdisciplinary collaboration and technological innovation.

Objective To monitor the susceptibility of clinical isolates to antimicrobial agents in healthcare facilities in major regions of China in 2023.Methods Clinical isolates collected from 73 hospitals across China were tested for antimicrobial susceptibility using a unified protocol based on disc diffusion method or automated testing systems.Results were interpreted using the 2023 Clinical & Laboratory Standards Institute (CLSI) breakpoints.Results A total of 445199 clinical isolates were collected in 2023,of which 29.0％ were gram-positive and 71.0％ were gram-negative.The prevalence of methicillin-resistant strains in Staphylococcus aureus,Staphylococcus epidermidis and other coagulase-negative Staphylococcus species (excluding Staphylococcus pseudintermedius and Staphylococcus schleiferi) (MRSA,MRSE and MRCNS) was 29.6％,81.9％ and 78.5％,respectively.Methicillin-resistant strains showed significantly higher resistance rates to most antimicrobial agents than methicillin-susceptible strains (MSSA,MSSE and MSCNS).Overall,92.9％ of MRSA strains were susceptible to trimethoprim-sulfamethoxazole and 91.4％ of MRSE strains were susceptible to rifampicin.No vancomycin-resistant strains were found.Enterococcus faecalis had significantly lower resistance rates to most antimicrobial agents tested than Enterococcus faecium.A few vancomycin-resistant strains were identified in both E.faecalis and E.faecium.The prevalence of penicillin-susceptible Streptococcus pneumoniae was 93.1％ in the isolates from children and and 95.9％ in the isolates from adults.The resistance rate to carbapenems was lower than 15.0％ for most Enterobacterales species except for Klebsiella,22.5％ and 23.6％ of which were resistant to imipenem and meropenem,respectively .Most Enterobacterales isolates were highly susceptible to tigecycline,colistin and polymyxin B,with resistance rates ranging from 0.6％ to 10.0％.The resistance rate to imipenem and meropenem was 21.9％ and 17.4％ for Pseudomonas aeruginosa,respectively,and 67.5％ and 68.1％ for Acinetobacter baumannii,respectively.Conclusions Increasing resistance to the commonly used antimicrobial agents is still observed in clinical bacterial isolates.However,the prevalence of important crabapenem-resistant organisms such as crabapenem-resistant K.pneumoniae,P.aeruginosa,and A.baumannii showed a slightly decreasing trend.This finding suggests that strengthening bacterial resistance surveillance and multidisciplinary linkage are important for preventing the occurrence and development of bacterial resistance.

Injury biomechanics is an interdisciplinary field that studies the biomechanical responses and injury mechanisms of the human body under external loads.The goal is to provide scientific foundations for the prevention,diagnosis,and treatment of human injuries.This field is widely applied in clinical medicine,sports science,rehabilitation engineering,traffic safety,aerospace,and other domains.In this review,the research progress in injury biomechanics in the year 2023 is summarized,focusing on in-depth analysis of injury mechanisms,innovations in injury prediction and protective countermeasure,and the latest applications of injury diagnosis and rehabilitation technologies.By systematically reviewing the research advancements,this review aims to offer new directions and ideas to the continued development of injury biomechanics and promote interdisciplinary collaboration and technological innovation.