Objective To investigate dynamic changes in myocardial protein phosphorylation during the acute phase of myocardial infarction (MI) in mice. Methods Six 8-week-old C57BL/6J mice were randomly assigned to MI model (n＝3) or sham-operated control (n＝3) groups. Cardiac tissues were harvested 72 hours post-intervention for proteomic analysis. Phosphorylation modifications were systematically characterized using liquid chromatography-mass spectrometry (LC-MS). Bioinformatics analyses included differential phosphorylation screening, functional enrichment, hierarchical clustering, and protein-protein interaction network. Results LC-MS identified 1 921 differentially phosphorylated sites (20 tyrosine and 1 901 serine/threonine sites) across 851 proteins. Compared with controls, MI hearts exhibited significant phosphorylation upregulation at 1 545 sites and downregulation at 376 sites (P＜0.05). Conclusions This study delineates MI-associated phosphorylation dynamics, providing mechanistic insights and potential therapeutic targets for acute MI intervention.

Objectives:This study aimed to investigate the impact of quantitative flow ratio(QFR)-guided revascularization on outcome of elderly patients with coronary artery disease(CAD)undergoing valve surgery.Methods:We retrospectively analyzed 750 consecutive patients with angiographically confirmed CAD(≥50%stenosis)who underwent valve surgery at Zhongshan Hospital,Fudan University,between January 2016 and December 2021.According to the patients'ages,they were divided into the younger group(age<70 years old,n=532)and the elderly group(age≥70 years old,n=218).Revascularization strategies were evaluated using anatomical(angiography-based)and functional(QFR-based)criteria.Anatomical complete revascularization(CR)was defined as bypass grafting for all lesions with≥70%diameter stenosis in major coronary arteries or≥50%stenosis in the left main coronary artery.Functional CR referred bypass grafting for all lesions with QFR≤0.80.Incomplete revascularization(ICR)was defined as failure to meet CR criteria.According to the anatomical and functional definitions,the younger group and the elderly group were further divided into the incomplete revascularization subgroup and the complete revascularization subgroup respectively.Major adverse cardiovascular events(MACE),including death,myocardial infarction,repeat revascularization,and stroke,were assessed as the composite endpoint.Results:Over a follow-up of(3.7±1.8)years,the overall MACE rate was 13.3%.The younger group exhibited significantly lower MACE rates than the elderly group(10.7%vs.19.7%,P=0.001).In the younger group,anatomical ICR did not increase MACE risk(HR=1.46,95%CI:0.81-2.62,P=0.164),whereas functional ICR significantly increased MACE risk(HR=2.27,95%CI:1.24-4.15,P=0.001).In the elderly group,neither anatomical ICR(HR=1.22,95%CI:0.62-2.41,P=0.540)nor functional ICR(HR=1.52,95%CI:0.78-2.96,P=0.172)was associated with increased MACE risk.Conclusions:In patients undergoing valve surgery with CAD,functional ICR correlated with adverse outcomes in the younger group,whereas neither anatomical nor functional ICR significantly affected prognosis in elderly patients.These findings suggest that a moderately conservative revascularization strategy may be more appropriate for elderly populations.

Objectives:This study aimed to investigate the impact of quantitative flow ratio(QFR)-guided revascularization on outcome of elderly patients with coronary artery disease(CAD)undergoing valve surgery.Methods:We retrospectively analyzed 750 consecutive patients with angiographically confirmed CAD(≥50%stenosis)who underwent valve surgery at Zhongshan Hospital,Fudan University,between January 2016 and December 2021.According to the patients'ages,they were divided into the younger group(age<70 years old,n=532)and the elderly group(age≥70 years old,n=218).Revascularization strategies were evaluated using anatomical(angiography-based)and functional(QFR-based)criteria.Anatomical complete revascularization(CR)was defined as bypass grafting for all lesions with≥70%diameter stenosis in major coronary arteries or≥50%stenosis in the left main coronary artery.Functional CR referred bypass grafting for all lesions with QFR≤0.80.Incomplete revascularization(ICR)was defined as failure to meet CR criteria.According to the anatomical and functional definitions,the younger group and the elderly group were further divided into the incomplete revascularization subgroup and the complete revascularization subgroup respectively.Major adverse cardiovascular events(MACE),including death,myocardial infarction,repeat revascularization,and stroke,were assessed as the composite endpoint.Results:Over a follow-up of(3.7±1.8)years,the overall MACE rate was 13.3%.The younger group exhibited significantly lower MACE rates than the elderly group(10.7%vs.19.7%,P=0.001).In the younger group,anatomical ICR did not increase MACE risk(HR=1.46,95%CI:0.81-2.62,P=0.164),whereas functional ICR significantly increased MACE risk(HR=2.27,95%CI:1.24-4.15,P=0.001).In the elderly group,neither anatomical ICR(HR=1.22,95%CI:0.62-2.41,P=0.540)nor functional ICR(HR=1.52,95%CI:0.78-2.96,P=0.172)was associated with increased MACE risk.Conclusions:In patients undergoing valve surgery with CAD,functional ICR correlated with adverse outcomes in the younger group,whereas neither anatomical nor functional ICR significantly affected prognosis in elderly patients.These findings suggest that a moderately conservative revascularization strategy may be more appropriate for elderly populations.

BACKGROUND:In recent years,High-definition transcranial direct current stimulation(HD-tDCS)has garnered significant attention due to its potential non-invasive modulation of brain function.However,there is still a lack of visual analysis in the literature regarding this technique. OBJECTIVE:To perform a visual analysis of HD-tDCS-related research so as to explore the current status and trends in this field. METHODS:English literature related to HD-tDCS was retrieved from the Web of Science Core Collection database covering the period from January 1,2010 to May 6,2023.The VOSviewer software was used to visualize and analyze the source journals,countries/regions,authors,institutions,cited references,and keywords of the included literature,creating a knowledge map to uncover the research landscape and hotspots. RESULTS AND CONCLUSION:A total of 336 articles were included,showing a consistent increase in the annual publication count of HD-tDCS research.Among these,the United States contributed the highest number of publications(141 articles)with 4 221 citations,followed by China with 70 articles and 401 citations.Brain Stimulation was the most prolific journal(28 articles),Marom Bikson was the most productive author(37 articles),and The City College of New York was the most active institution(35 articles).The most frequently mentioned keywords in the field included motor cortex,regulation,working memory,excitability,and dorsolateral prefrontal cortex.Notable recent keywords in the last 5 years include attention-deficit/hyperactivity disorder,brain networks,and stimulation intensity.Currently,the volume of HD-tDCS research is relatively limited,but is on an upward trajectory,indicating substantial research potential.It is expected that future studies in this domain will continue to focus on the application of HD-tDCS in cognitive and neuropsychiatric disorders,while also exploring its therapeutic mechanisms targeting the motor cortex and dorsolateral prefrontal cortex based on brain network analysis.

Objective:To explore the risk factors for postoperative adverse events in older persons with gastrointestinal malignancies and thus provide reference for selection of surgery and evaluation of such patients.Methods:An observational study design was employed, the study cohort comprising patients aged 65 years and over with gastrointestinal malignancies who underwent elective surgery in Peking University Cancer Hospital from 2008 to 2022. In this study, we compared the clinical characteristics (disease type, tumor stage), surgical safety (combined organ resection, operation duration, comorbidities), and treatment outcomes (postoperative complications, unplanned reoperation, and perioperative mortality) of these patients. Multivariate logistic regression analysis was conducted to identify risk factors associated with adverse outcomes.Results:The study cohort comprised 10,135 patients, of whom 74.7% (7,568) were 65–75 years old (excluding 75 years old), 23.6% (2,391) 75–85 years old (excluding 85 years old), and 1.7% (176) ≥85 years old. The type of cancer was colorectal in 63.4% (6,427 patients) and gastric in 36.6% (3,708); 62.0% (6,284/10,135)of the patients had stage II or III disease. The proportion of stage III and stage IV tumors was higher in patients aged over 85 years (47.4% [73/154) and 11.0% [17/154]), respectively, than in those aged 75–85 years (41.6% [854/2 051) and 8.2% [168/2 051]), respectively, and those aged 65–75 years (40.1% [2,576/6,431) and 10.9% [700/6,431]); these differences are statistically significant (χ 2=27.95, P<0.01). Comorbidity was present in 50.6% (5,128/10,135) of the whole study cohort, comprising 58.0% (102/176) of those aged over 85 years, this being significantly higher than the 56.3% (1,346/2,391) in those aged 75–85 years and 48.6% (3,678/7,568) of those aged 65–75 years. The main comorbidities were hypertension (37.3%), diabetes (16.4%), and cardiovascular and cerebrovascular diseases (14.0%). Minimally invasive surgery was performed on 36.9% (3,740/10,135) of the whole study cohort, the 38.4% in 65–75 years old patients being significantly higher than the 32.5% in those aged 75–85 years and the 29.0% in those aged over 85 years; these differences are statistically significant (χ 2=31.97, P<0.01). Preoperative neoadjuvant therapy was administered to 9.1% (924/10,135) of the whole study cohort, the proportion of patients receiving preoperative neoadjuvant therapy being significantly higher in those aged 65–75 years (11.1%) than in those aged 75–85 years (3.4%) and over 85 years (0.6%); these differences are statistically significant (χ 2=148.98, P<0.01). Combined organ resection was performed in 4.9% (496/10,135) of the whole study cohort, the proportion undergoing combined organ resection being significantly lower in those aged over 85 years (2.3%) than in those aged 65–75 years (5.3%) and 75–85 years (3.8%); these differences are statistically significant (χ 2=11.20, P<0.01). The mean operating time was (182.2±76.8) minutes, being significantly higher in those aged 65–75 years (186.6±78.3 minutes) than in those aged 75–85 years (169.4±71.3 minutes) and over 85 years (153.2±53.7 minutes); these differences are statistically significant ( F=46.85, P<0.01). The overall incidence of postoperative complications was 10.9% (802/7,384); the incidence did not differ significantly between the three groups ( P>0.05). The incidence of unplanned reoperation was 1.9% (193/10,135) and of death during hospitalization 0.3% (32/10,135). The perioperative mortality in the three groups was 1.1%, 0.5% and 0.2% in those aged over 85, 75–85, and 65–75 years, respectively. These differences are statistically significant (χ 2=9.71, P<0.01). Among the patients with postoperative complications, 15.0% (120/802) underwent unplanned reoperation, which had a perioperative mortality of 1.0% (8/802), these rates being significantly higher than those for unplanned reoperation (1.1%, 73/6,582) and perioperative mortality (0.4%, 24/6,582) in patients without complications (all P<0.01). The median length of hospital stay was 11 days in patients aged over 85 years; this is significantly longer than the 9 days in those aged 65–75 years and 10 days in those aged 75–85 years (H=37.00, P<0.01). Multivariate logistic regression analysis showed that tumor stage IV (OR=1.56, 95%CI: 1.24–1.96, P<0.01), comorbidities (OR=1.26, 95%CI: 1.08–1.47, P<0.01), open surgery (OR=1.33, 95%CI: 1.13–1.56, P<0.01), and operation time >180 minutes (OR=1.82, 95%CI:1.53–2.15, P<0.01) were risk factors for adverse outcomes. Conclusion:Older patients with gastrointestinal tumors who have comorbidities and stage IV disease and undergo open surgery with a longer operation time are at higher risk of adverse outcomes than patients without these characteristics.

Objective:To explore the risk factors for postoperative adverse events in older persons with gastrointestinal malignancies and thus provide reference for selection of surgery and evaluation of such patients.Methods:An observational study design was employed, the study cohort comprising patients aged 65 years and over with gastrointestinal malignancies who underwent elective surgery in Peking University Cancer Hospital from 2008 to 2022. In this study, we compared the clinical characteristics (disease type, tumor stage), surgical safety (combined organ resection, operation duration, comorbidities), and treatment outcomes (postoperative complications, unplanned reoperation, and perioperative mortality) of these patients. Multivariate logistic regression analysis was conducted to identify risk factors associated with adverse outcomes.Results:The study cohort comprised 10,135 patients, of whom 74.7% (7,568) were 65–75 years old (excluding 75 years old), 23.6% (2,391) 75–85 years old (excluding 85 years old), and 1.7% (176) ≥85 years old. The type of cancer was colorectal in 63.4% (6,427 patients) and gastric in 36.6% (3,708); 62.0% (6,284/10,135)of the patients had stage II or III disease. The proportion of stage III and stage IV tumors was higher in patients aged over 85 years (47.4% [73/154) and 11.0% [17/154]), respectively, than in those aged 75–85 years (41.6% [854/2 051) and 8.2% [168/2 051]), respectively, and those aged 65–75 years (40.1% [2,576/6,431) and 10.9% [700/6,431]); these differences are statistically significant (χ 2=27.95, P<0.01). Comorbidity was present in 50.6% (5,128/10,135) of the whole study cohort, comprising 58.0% (102/176) of those aged over 85 years, this being significantly higher than the 56.3% (1,346/2,391) in those aged 75–85 years and 48.6% (3,678/7,568) of those aged 65–75 years. The main comorbidities were hypertension (37.3%), diabetes (16.4%), and cardiovascular and cerebrovascular diseases (14.0%). Minimally invasive surgery was performed on 36.9% (3,740/10,135) of the whole study cohort, the 38.4% in 65–75 years old patients being significantly higher than the 32.5% in those aged 75–85 years and the 29.0% in those aged over 85 years; these differences are statistically significant (χ 2=31.97, P<0.01). Preoperative neoadjuvant therapy was administered to 9.1% (924/10,135) of the whole study cohort, the proportion of patients receiving preoperative neoadjuvant therapy being significantly higher in those aged 65–75 years (11.1%) than in those aged 75–85 years (3.4%) and over 85 years (0.6%); these differences are statistically significant (χ 2=148.98, P<0.01). Combined organ resection was performed in 4.9% (496/10,135) of the whole study cohort, the proportion undergoing combined organ resection being significantly lower in those aged over 85 years (2.3%) than in those aged 65–75 years (5.3%) and 75–85 years (3.8%); these differences are statistically significant (χ 2=11.20, P<0.01). The mean operating time was (182.2±76.8) minutes, being significantly higher in those aged 65–75 years (186.6±78.3 minutes) than in those aged 75–85 years (169.4±71.3 minutes) and over 85 years (153.2±53.7 minutes); these differences are statistically significant ( F=46.85, P<0.01). The overall incidence of postoperative complications was 10.9% (802/7,384); the incidence did not differ significantly between the three groups ( P>0.05). The incidence of unplanned reoperation was 1.9% (193/10,135) and of death during hospitalization 0.3% (32/10,135). The perioperative mortality in the three groups was 1.1%, 0.5% and 0.2% in those aged over 85, 75–85, and 65–75 years, respectively. These differences are statistically significant (χ 2=9.71, P<0.01). Among the patients with postoperative complications, 15.0% (120/802) underwent unplanned reoperation, which had a perioperative mortality of 1.0% (8/802), these rates being significantly higher than those for unplanned reoperation (1.1%, 73/6,582) and perioperative mortality (0.4%, 24/6,582) in patients without complications (all P<0.01). The median length of hospital stay was 11 days in patients aged over 85 years; this is significantly longer than the 9 days in those aged 65–75 years and 10 days in those aged 75–85 years (H=37.00, P<0.01). Multivariate logistic regression analysis showed that tumor stage IV (OR=1.56, 95%CI: 1.24–1.96, P<0.01), comorbidities (OR=1.26, 95%CI: 1.08–1.47, P<0.01), open surgery (OR=1.33, 95%CI: 1.13–1.56, P<0.01), and operation time >180 minutes (OR=1.82, 95%CI:1.53–2.15, P<0.01) were risk factors for adverse outcomes. Conclusion:Older patients with gastrointestinal tumors who have comorbidities and stage IV disease and undergo open surgery with a longer operation time are at higher risk of adverse outcomes than patients without these characteristics.

A series of new monobactam sulfonates is continuously synthesized and evaluated for their antimicrobial efficacies against Gram-negative bacteria. Compound 33a (IMBZ18G) is highly effective in vitro and in vivo against clinically intractable multi-drug-resistant (MDR) Gram-negative strains, with a highly druglike nature. The checkerboard assay reveals its significant synergistic effect with β-lactamase inhibitor avibactam, and the MIC values against MDR enterobacteria were reduced up to 4-512 folds. X-ray co-crystal and chemoproteomic assays indicate that the anti-MDR bacteria effect of 33a results from the dual inhibition of the common PBP3 and some class A and C β-lactamases. Accordingly, preclinical studies of 33a alone and 33a‒avibactam combination as potential innovative candidates are actively going on, in the treatment of β-lactamase-producing MDR Gram-negative bacterial infections.

Esophageal squamous cell carcinoma (ESCC) is one of the most common malignant tumors with a poor prognosis. 4-nitroquinoline-1-oxide (4NQO) is a water-soluble quinoline derivative that can successfully induce the production of squamous cell carcinoma in vivo. Establishing and optimizing experimental methods for 4NQO induced ESCC formation in mice can provide a more suitable in situ model for the study of ESCC.

Aortic dissection (AD) is a life-threatening vascular disease due to the tearing of aortic intimal layer, leading to the formation of pseudocavity. Once the acute progression of dissection happens, serious complications such as rupture and stroke may occur. The current imaging examinations for AD are invasive and may cause adverse effects related to contrast medium, which cannot be used for large-scale screening of AD. The latest studies have found that metabolic processes and metabolites of lipids,saccarides and proteins are involved in the pathogenesis and development of AD. In this article, we review the research progress in the caracteristics of AD related metabolism,summarize changes of specific metabolites in AD,and explore the clinical implication of studies on AD related metaboliome..

Objective:To evaluate the efficacy and safety of drug-coated balloon (DCB) with paclitaxel in the treatment of femoropopliteal artery in-stent restenosis.Methods:From Dec 2016 to Jul 2020, clinical and follow-up data of femoropopliteal artery in-stent restenosis (ISR) treated with paclitaxel DCB were retrospectively analyzed.Results:Firty-two patients (56 lower limbs) with femoropopliteal artery ISR underwent DCB therapy. According to Rutherford classification, 1 case was R2 (1.7%), 9 cases were R3 (23.2%), 23 cases were R4 (41.1%), 15 cases were R5 (26.8%) and 4 cases were R6 (7.1%). According to Tosaka classification of ISR, 46 (81.2%)limbs were Tosaka Ⅱ, 10(17.9%)limbs were Tosaka Ⅲ Mean lesion length of ISR was (240±122)mm. Bail-out stent implantation was performed in 25% cases. The median follow-up time was 18 months. The all-cause mortality rate was 11.8%, the major amputation rate was 5.9%, the primary patency rate was 53.4%, the primary assisted patency rate was 67.1%, the secondary patency rate was 93.2%, and the F-TLR was 77.2%.Conclusion:DCB is a safe and effective endovascular therapy for femoropopliteal artery ISR.