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.

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..

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.

Objective:To investigate the diagnostic value of vaginal color Doppler flow parameters in patients with epithelial ovarian cancer in different FIGO staging.Methods:178 patients with ovarian tumors who were treated by surgery in Dingzhou People’s Hospital from Jul. 2016 to Jul. 2022 were selected, and they were divided into ovarian cancer group (65 cases) and ovarian cyst group (113 cases) according to the results of postoperative pathological diagnosis. According to FIGO staging standards, ovarian cancer was divided into FIGO stage I (18 cases) , FIGO stage II (16 cases) , FIGO stage III (16 cases) and FIGO stage IV (15 cases) . The blood flow parameters of vaginal color Doppler ultrasound were measured, including arterial pulsatility index (PI) , end diastolic flow velocity (EDV) , resistance index (RI) , peak flow velocity (PSV) , serum vascular endothelial growth factor (VEGF) and human epididymal epithelial secretory protein 4 (HE4) . The levels of PI, EDV, RI, PSV, VEGF and HE4 were compared between the two groups and patients with different FIGO stages, and the value of ROC analysis of vaginal color Doppler flow parameters in predicting the occurrence of ovarian cancer was analyzed. The correlation between FIGO stage and vaginal color Doppler flow parameters and serum VEGF and HE4 levels was analyzed by person coefficient.Results:PI and RI levels in ovarian cancer group were (0.79 ± 0.15) , and (0.39 ± 0.12) , lower than those in ovarian cyst group (1.51 ± 0.17) , (0.72 ± 0.16) ; EDV, PSV, HE4, VEGF levels were (13.88 ± 4.18) cm/s, (25.61 ± 4.53) cm/s, (283.92 ± 28.97) pmol/L, and (372.55 ± 38.96) ng/mL, higher than those in ovarian cyst group ( P<0.05) . According to ROC analysis, the best cutoff values of transvaginal color Doppler blood flow parameters for predicting the occurrence of ovarian cancer were PI<1.235, EDV≥10.985 cm/s, RI<0.580, PSV≥22.975cm/s, all P<0.05. The levels of PI and RI in patients with different FIGO stages showed a decreasing trend with the increase of the severity of the disease, while the levels of EDV, HE4 and VEGF showed an increasing trend ( P<0.05) . There was no significant difference in PSV levels between patients with different FIGO stages ( P>0.05) . The correlation analysis showed that FIGO stage was positively correlated with the blood flow parameters EDV and the levels of serum HE4 and VEGF. FIGO stage was negatively correlated with PI and RI ( P<0.05) . Conclusions:There were significant differences in the levels of PI, RI and EDV in patients with ovarian cysts and ovarian cancer at different FIGO stages. The levels of PI, RI and EDV are closely related to the malignant degree of ovarian cancer.

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.

Hypoxia inducible factor-1 (HIF-1) is the main transcription factor and the core regulator for cells to adapt to hypoxia, and oxygen homeostasis is achieved by controlling and utilizing oxygen delivery. Autophagy and apoptosis play an important role in determining cell fate and maintaining cell homeostasis. In recent years, it has been found that the dynamic change of HIF-1 expression plays a key role in the hypoxic adaptive response of cardiomyocytes. The regulation of HIF-1 on autophagy and apoptosis of hypoxic cardiomyocytes determines the survival of cardiomyocytes, which is of great significance for the prognosis of ischemic heart disease.