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.

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 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 investigate the effect of instantaneous flow rate on the consistency of diagnostic accuracy of severe degenerative mitral regurgitation (DMR) using proximal isovelocity surface area (PISA).Methods:From June 2019 to June 2021, 75 patients with DMR who underwent echocardiography in Department of Echocardiography of Zhongshan Hospital, Fudan University were prospectively enrolled. The instantaneous flow rate of DMR during the systolic phase was calculated using M-mode PISA(PISA M-mode), and a time-integrated curve was plotted. Regurgitant volume (RVol) and effective regurgitant orifice area (EROA) were calculated by traditional PISA (PISA max), pair PISA (PISA pair), and PISA M-mode, respectively. RVol acquired from cardiac magnetic resonance (CMR) volumetric method in 22 patients of the enrolled patients. The correlation and consistency of RVol acquired between the three PISA methods and CMR were compared. Agreement of diagnostic accuracy of severe mitral regurgitation (sMR) acquired between the three PISA methods and multi-parameter algorithm by American Society of Echocardiography (ASE) was analyzed using Cohen′s Kappa analysis. Results:The curve of instantaneous flow rate of DMR showed unimodal pattern with the peak at mid-late systolic phase. The correlation of RVol acquired between PISA methods and CMR was moderate for PISA max and PISA pair ( r=0.77, 0.80, both P<0.001), whereas PISA M-mode presented strong correlation with CMR ( r=0.87, P<0.001). RVol acquired from PISA max was larger than that of CMR[(69.1±37.1) ml vs (49.0±29.0)ml, P=0.002]. Both PISA max and PISA pair were shown moderate agreement of diagnostic accuracy of sMR with ASE multi-parameters algorithm (RVol: κ=0.496, 0.525, both P<0.001; EROA: κ=0.570, 0.578, both P<0.001), while PISA M-mode presented strong agreement (RVol: κ=0.867 and EROA: κ=0.802, both P<0.001). Conclusions:Based on the unimodal pattern of instantaneous flow rate in patients with DMR, PISA max may significantly overestimate RVol, exposing a significant proportion of patients with DMR to unnecessary MR surgery. PISA M-mode presents better correlation and consistency with CMR on the quantification of RVol compared with PISA max and PISA pair, and may improve the diagnostic accuracy of quantification of sMR using PISA.

Objective:To study the learning curve of percutaneous patent foramen ovale (PFO) occlusion guided solely by transthoracic echocardiography (TTE), as well as the success rate and safety of the learning curve.Methods:To retrospectively analyze these patients with indications for PFO occlusion admitted in our department from April 2021 to April 2022, and obtained 100 samples the author's initial cases guided solely by TTE, including 25 men and 75 women, with a mean age of (48.22±10.44) years old.Analyze preoperative baseline data: gender, age, height, weight, body mass index, the tunnel length and size of the PFO measured by transesophageal echocardiography, the grade of contrast-transcranial doppler test, combined atrial septal aneurysm, etc.Operation time, success rate, and complications were analyzed in all patients.Results:With the accumulation of cases, the operation time gradually shortened, accumulated to about 50 cases, the operation time has significantly shortened ( P<0.05), and the learning curve was leveled off after 50 cases ( P<0.05), there was statistical difference.The comparison of the success rate and complication of cases within the learning curve and those after completing the learning curve was no statistical significance( P>0.05). Conclusion:The learning curve of percutaneousc closure of patent foramen ovale guided solely by TTE is long, requiring about 50 cases to complete the learning curve. The success rate and safety of the learning curve are high. This procedure is worth popularizing.

Objective:To establish an animal model of chronic systemic inflammation with long-term high expression of circulating IL-6 by introducing exogenous IL-6 gene transfer vector.Methods:Recombinant murine IL-6-encoding adeno-associated virus (AAV-IL-6) was constructed. Twenty-one 24-week-old male C57BL/6J mice were randomly divided into three groups with seven in each group: AAV-IL-6 group, vector control (AAV-ctrl) group and blank control group. At 0, 8 and 16 weeks of intervention, the mice in the three groups were injected with AAV-IL-6 (100 μl 0.5×10 10 vp/ml), unloaded AAV (100 μl 0.5×10 10 vp/ml) and the same volume of saline in the tail vein, respectively. IL-6 levels in mouse serum were measured by ELISA. The general condition of mice was observed and blood routine tests were performed. Changes in blood biochemical parameters and C-reactive protein (CRP) levels were detected. At the end of 24-week intervention, the mice were sacrificed and the myocardium, liver, spleen, quadriceps femoris, knee joint and middle femur were taken for HE staining. Results:At 4, 8, 16 and 24 weeks after intervention, serum IL-6 levels were (75.41-169.28) pg/ml in the AAV-IL-6 group, while in the two control groups, the levels were below the lower limit of detection (7.8 pg/ml). At 24 weeks after intervention, the body weight of mice in the AAV-IL-6 group was significantly lower than that of mice in the two control groups; the neutrophil counts and CRP level in the AAV-IL-6 group were higher than those in the two control groups, while the levels of albumin, creatinine, triglyceride and cholesterol were lower than those in the two control groups. There were no differences in the aforementioned parameters between the two control groups. Compared with the blank control group, both AAV-IL-6 and AAV-ctrl groups showed increased lymphocyte counts. All mice had normal liver and kidney functions at the end of intervention. Histopathological findings indicated that the mice in the AAV-IL-6 group had focal infiltration of lymphocytes in the central venous area of the liver and around the myocardial and the skeletal muscle fibers, diffuse infiltration of multinucleated giant cells in the spleen, atrophic skeletal muscle, disorganized growth plate, reduced chondrocyte hypertrophic zone, thinner bone cortex and trabecular, and reduced osteoid. There were no histopathological changes in mice of the two control groups.Conclusions:Repeated tail vein injection of AAV-IL-6 could achieve long-term high expression of circulating IL-6 in mice, which manifested the phenotype of chronic systemic inflammation in preliminary detection and provided a safe, effective and simply accessible animal model for related studies.

Objective:To evaluate the diagnostic performance of non-contrast-enhanced Dixon water-fat separation Compressed SENSE (CS-SENSE) whole-heart coronary magnetic resonance angiography (CMRA) at 3.0 T on patients with suspected coronary artery disease (CAD).Method:The study complied with the Declaration of Helsinki. Local ethics committee approved this study and written informed consent was obtained from each patient. In this prospective study, from March 2021 to September 2021, 53 consecutive participants with suspected CAD who were scheduled for X-ray coronary angiography (CAG) were prospectively recruited in Zhongshan Hospital. CMRA was performed with a 3.0 T scanner without contrast agent enhancement during free breathing with Dixon water-fat separation and CS-SENSE methods. The accuracy of CMRA for detecting a ≥ 50% reduction in diameter was determined using CAG as the reference method.Results:Acquisition of whole-heart CMRA images was successfully performed in 46 (86.8%) of 53 patients with an average imaging time of (7.8±1.8) min. The sensitivity, specificity, positive predictive values, negative predictive values, and accuracy of CMRA according to a patient-based analysis were 95.8%(95%CI 78.9%-99.9%), 81.8%(95%CI 59.7%-94.8%), 85.2%(95%CI 66.3%-95.8%), 94.7%(95%CI 74.0%-99.9%), 89.1%(95%CI 76.4%-96.4%), respectively. The areas under the receiver-operator characteristic curve (AUC) from CMRA images according to patient-, vessel-and segment-based analyses were 0.876(95%CI 0.745-0.955), 0.880(95%CI 0.814-0.929), 0.903(95%CI 0.877-0.926), respectively.Conclusion:3.0 T non-contrast-enhanced Dixon water-fat separation CS-SENSE whole-heart CMRA is a promising technique to detect clinically significant coronary stenosis on patients with suspected CAD.

Objective 聽 聽To investigate the influence of mechanical and biological valves on clinical benefits of elderly patients with valvular heart disease. Methods 聽 聽We retrospectively analyzed the clinical data of 280 elderly patients with valvular heart disease treated by valve replacement between 2008 and 2014 year. The patients were divided into two groups by tendency score matching including a group A with biological valves and a group B with mechanical valves. Finally, there were 96 patients in each group. There were 43 males and 53 females at age of 64.41卤6.52 years in the group A, 44 males and 52 females at age of 64.07卤6.20 years in the group B. Results 聽 聽The bleeding rate of skin and mucosa of the group B was significantly higher than that of the group A (P<0.05). There was no statistical difference in mortality within 30 days after operation, all-cause mortality, re-hospitalization rate, re-valve replacement rate, combined atrial flutter/atrial fibrillation ratio, drug use, incidence of cerebral infarction, cerebral hemorrhage, new peripheral vascular embolism and visceral hemorrhage, heart function (NYHA) classification, the cumulative survival rate of all the patients during follow-up (P=0.63), or the cumulative survival rate of the patients with no thrombus/hemorrhage (P=0.75) between the two groups (P>0.05). Conclusion 聽 聽Mechanical valve replacement and bioprosthetic valve replacement in the treatment of valvular heart disease in the elderly can achieve similar clinical benefits and both have clinical application value.

Anatomy is an important medical course for international medical students. In order to improve the teaching quality and enhance the extent of students' learning, teachers integrated the theoretical and experimental courses of systemic anatomy, and introduced the "Digital Human" anatomical system to compensate the shortage of models, so as to realize the integrated theory and experiment teaching of systematic anatomy. Practice indicated that integrated teaching mode of theory and experiment was more consistent with the learning habits of foreign students, which improved their learning effect with significant advantages. But there were still some problems in this teaching mode and measures for solving these problems were proposed in this paper.