Background:Severe coronary anatomical involvement is clinically important in patients with acute coronary syndrome (ACS), yet evidence on its relationship with insulin sensitivity remains limited. This study examined the association of the single-point insulin sensitivity estimator (SPISE), a simple surrogate marker of insulin sensitivity, with severe coronary anatomical patterns, including left main and/or three-vessel disease and isolated three-vessel disease, in middle-aged and older patients with ACS. Methods:This cross-sectional analysis was based on data from the CCC-ACS project. A total of 16,383 patients were included in the analysis of left main and/or three-vessel disease, and 13,390 patients were included in the analysis of isolated three-vessel disease. SPISE was analyzed as both a continuous variable and according to tertiles. Multivariable logistic regression was used to evaluate the associations between SPISE and the study outcomes. Restricted cubic spline analyses were performed to assess dose-response patterns, and subgroup and sensitivity analyses were conducted to examine the robustness of the findings. Results:Higher SPISE was associated with lower odds of both severe coronary anatomical outcomes. In the fully adjusted model, each 1-unit increase in SPISE was associated with lower odds of left main and/or three-vessel disease (OR, 0.977; 95% CI, 0.957-0.998) and isolated three-vessel disease (OR, 0.957; 95% CI, 0.935-0.980). Compared with patients in the lowest SPISE tertile, those in the highest tertile had lower odds of both outcomes. Restricted cubic spline analyses supported dose-response relationships. Subgroup analyses suggested age-related heterogeneity, with the inverse associations mainly observed in patients aged <65 years and attenuated among those aged ≥65 years. Sensitivity analyses yielded generally consistent results. Conclusion:Among ACS patients aged 45 years or older, higher SPISE was associated with lower odds of severe coronary anatomical involvement, with this association mainly evident in patients aged <65 years. These findings support a potential link between reduced insulin sensitivity and angiographically defined severe coronary anatomical involvement and suggest that SPISE may serve as a readily available marker for identifying patients more likely to have high-risk coronary anatomy.

PURPOSE:Chemotherapy-related cognitive impairment (CRCI) is a prevalent neurotoxicity in patients with breast cancer (BC), leading to cognitive decline and reduced quality of life. Exercise is recommended as a potential strategy to mitigate CRCI; however, optimal exercise modalities and protocols remain unclear. Moreover, implementing exercise during chemotherapy presents practical and adherence challenges, highlighting the need for feasible, targeted exercise interventions. This study aimed to evaluate the effects of an aerobic exercise programme delivered throughout chemotherapy on cognitive function in patients with BC. METHODS:A non-randomized controlled clinical trial was conducted in patients aged 18-65 years with stage I-III breast cancer undergoing chemotherapy. Participants received either usual care or an aerobic exercise-based programme delivered throughout chemotherapy, incorporating behavioural and social support components. Subjective and objective cognitive function, fatigue, quality of life, and physical fitness were assessed at baseline, mid-chemotherapy, and post-intervention. RESULTS:Fifty-nine patients (intervention group, n = 28 vs. control group, n = 31) were enrolled into the study, and 48 (24 per group) completed all tests at final-chemotherapy. Compared with the control group, significant improvements were observed in all measurements of cognitive function, fatigue, quality of life, and grip strength (healthy) after the intervention (p < .05). CONCLUSION:The aerobic exercise-based program had beneficial effects on cognitive function, fatigue, quality of life, and grip strength.

BACKGROUND AND OBJECTIVES:Transradial access (TRA) is recommended for percutaneous coronary intervention (PCI) in ST-elevation myocardial infarction (STEMI) due to lower mortality and bleeding risk, but evidence in STEMI with cardiogenic shock (STEMI-CS) remains limited. To evaluate the efficacy and safety of TRA versus transfemoral access (TFA) for primary PCI in STEMI-CS. METHODS:Using data from a nationwide, multicenter registry, we compared TRA and TFA with multivariable-adjusted Cox regression, propensity score matching, and inverse probability treatment weighting. The primary outcome was in-hospital all-cause mortality. Other outcomes included major bleeding and major adverse cardiovascular events (MACE), defined as a composite of all-cause mortality, cardiac arrest, reinfarction, stroke, or in-stent thrombosis. A meta-analysis was conducted to compare short-term outcomes of interest during hospitalization or within 30 days of hospital discharge. RESULTS:Among 837 eligible patients, 669 underwent TRA. Multivariable Cox regression showed that TRA was associated with a lower risk of in-hospital mortality (adjusted hazard ratio [HR], 0.62; 95% confidence interval [CI], 0.42-0.91), MACE (adjusted HR, 0.63; 95% CI, 0.43-0.91), but a non-significantly lower risk of major bleeding (adjusted HR, 0.72; 95% CI, 0.35-1.49) compared to TFA. Meta-analysis of 65,943 patients from 17 studies confirmed lower short-term mortality (odds ratio [OR], 0.50; 95% CI, 0.43-0.57), major bleeding (OR, 0.58; 95% CI, 0.48-0.71), and MACE (OR, 0.65; 95% CI, 0.53-0.80) with TRA. CONCLUSIONS:Our findings indicate that, in STEMI-CS, TRA is associated with lower short-term all-cause mortality compared with TFA, supporting the potential advantages of TRA in this population. TRIAL REGISTRATION:ClinicalTrials.gov Identifier: NCT02306616.

BackgroundThis study aimed to evaluate and compare the predictive performance of the National Institutes of Health Stroke Scale (NIHSS) assessed at baseline, at 24 h, and derived change metrics for 90-day unfavorable functional outcome (modified Rankin Scale 3–6) in cardioembolic stroke patients with Anterior Circulation Occlusion (ACO) post-endovascular thrombectomy (EVT).MethodsA retrospective analysis of 103 eligible patients was performed. Univariate and multivariate logistic regression identified predictors. Receiver operating characteristic (ROC) curve analysis and DeLong’s test compared the predictive performance of baseline NIHSS, 24-h NIHSS, ΔNIHSS (baseline NIHSS − 24-h NIHSS) and the percent ΔNIHSS (ΔNIHSS × 100/baseline NIHSS).ResultsMultivariate analysis confirmed 24-h NIHSS, baseline NIHSS, ΔNIHSS, and percent ΔNIHSS as independent predictors. ROC analysis showed that 24-h NIHSS had the highest predictive power (AUC = 0.850), significantly outperforming baseline NIHSS (AUC = 0.702), ΔNIHSS (AUC = 0.735), and percent ΔNIHSS (AUC = 0.780). The optimal cut-off value was ≥12, with 82.2% sensitivity and 75.6% specificity. Combining 24-h NIHSS with other NIHSS-based metrics did not improve predictive performance compared to 24-h NIHSS alone.ConclusionThe 24-h NIHSS score is the strongest prognostic predictor of 90-day unfavorable functional outcome in cardioembolic stroke patients post-EVT, superior to baseline scores, ΔNIHSS and percent ΔNIHSS. It serves as an early and effective tool for prognostic stratification.

In-hospital cardiac arrest (IHCA) is an infrequent but lethal complication in patients with ST-elevation myocardial infarction (STEMI). Data on the characteristics and predictors of IHCA in STEMI patients after successful primary percutaneous coronary intervention (PPCI) are limited. This study aimed to identify the risk factors of IHCA and construct a predictive nomogram. A total of 5121 STEMI patients treated with successful PPCI from January 2018 to July 2023 at Beijing Anzhen Hospital were retrospectively enrolled in our study. Subjects were randomly divided into a development group and a validation group in a 7:3 ratio. Optimal predictive variables were selected using the least absolute shrinkage and selection operator (Lasso) and logistic regression models. A nomogram based on these predictors was then created to estimate IHCA probability. Among them, 94 patients (1.8

Endothelial-to-mesenchymal transition (EndMT) is a critical pathophysiological process in fibrosis which is associated with large conductance calcium-activated potassium (BKCa) channels. Apelin, an adipokine, was reported to alleviate glomerular EndMT mainly caused by hyperglycemia in diabetic nephropathy (DN) and related to BKCa. Therefore, it is supposed that apelin reduced glomerular EndMT by increasing BKCa in glomerular endothelial cells (GECs). The results showed that apelin inhibited diabetic glomerular fibrosis and EndMT in vivo and in vitro, such as increasing endothelial markers CD31, VE-Cadherin and decreasing mesenchymal α-SMA, Desmin, which were reversed after specific APJ knockout in endothelial cells. Meanwhile, apelin increased BKCa, and the suppressed effect of apelin on Wnt/β-Catenin signaling pathway was canceled after BKCa was inhibited by Iberiotoxin (IBTX) in GECs under high glucose condition. Furthermore, IBTX also inhibited SP1 translocation into nuclei, followed by increased expression of DKK1 in apelin treated GECs under high glucose condition. In conclusion, apelin/APJ alleviated EndMT in diabetic glomerular fibrosis by inhibiting the Wnt/β-Catenin pathway, which was mediated by BKCa activated SP1, leading to an increased expression of DKK1 in GECs.

AIMS:The superior vena cava (SVC) has been implicated as a non-pulmonary vein trigger in the initiation and maintenance of atrial fibrillation (AF). However, the incremental benefit of empiric SVC isolation (SVCI) in addition to pulmonary vein isolation (PVI) for paroxysmal AF (PAF) remains inconclusive. This study aimed to determine whether adding empiric SVCI to PVI improves freedom from atrial arrhythmia (ATA) recurrence in patients with PAF. METHODS AND RESULTS:A total of 302 patients with PAF, aged 18-75 years, undergoing index ablation, were enrolled and randomized in a 1:1 ratio to either the PVI plus SVCI group or the PVI alone group between May 2021 and February 2024. In the PVI plus SVCI group, PVI was performed first, followed by empiric SVCI. In the PVI alone group, only PVI was performed. Among 302 randomized patients [median (IQR) age, 64.9 (56.0-70.0) years, 165 men (54.6%)], 302 (100%) completed the 3-month blanking period and contributed to the efficacy analysis. After a median follow-up of 20 months, the recurrence of rate of ATAs did not differ significantly between the PVI plus SVCI group (20/151 patients, 13.2%) and PVI alone group (29/151, 19.2%) without taking antiarrhythmic drugs (hazard ratio, 0.68, 95% confidence interval 0.38-1.20, P = 0.182). Subgroup outcomes analysis further demonstrated no significant interaction across subgroups. CONCLUSION:Among patients with PAF undergoing initial ablation, the addition of empiric SVCI to PVI, compared with PVI alone, did not significantly improve freedom from ATA recurrence. CLINICAL TRIAL REGISTRATION:This study was registered with Chinese Clinical Trials Registry: ChiCTR220005554.

This study explores the prevalence of hypertension in patients with type 2 diabetes mellitus (T2DM) and identifies the potential risk factors associated with the development of hypertension. A cross-sectional study was conducted among 699 T2DM patients. Demographic data and clinical parameters were collected using structured questionnaires and physical examinations. Binary logistic regression was used to assess associations between hypertension and potential risk factors, adjusting for confounders. Body mass index was positively associated with uric acid levels and high-density lipoprotein cholesterol (HDL-c) in the non-hypertensive group. In the hypertensive group, HDL-c was positively correlated with fasting insulin, postprandial insulin, and triglycerides. The primary factors associated with hypertension in patients with T2DM include glycosylated hemoglobin A1C (odds ratio [OR] = 0.54, 95% confidence interval [CI]: 0.32–0.92, P = .02), HDL-c (OR = 0.54, 95% CI: 0.23–0.86, P = .02), education level (OR = 0.44, 95% CI: 0.23–0.82, P = .01), lactate dehydrogenase (OR = 1.01, 95% CI: 1.00–1.02, P = .01), urinary albumin-to-creatinine ratio (OR = 0.97, 95% CI: 0.94–1.00, P = .03), and microalbumin (OR = 1.01, 95% CI: 1.00–1.01, P = .02). Hemoglobin A1c, HDL-c, lactate dehydrogenase, urinary albumin-to-creatinine ratio, microalbumin, and postprandial insulin are critical predictors of hypertension in individuals with T2DM. In conjunction with lifestyle modifications aimed at weight management and glycemic control, regular monitoring of these biomarkers is recommended to prevent hypertension in diabetes management.

Regulatory T cells (Tregs) have been documented to accumulate in damaged myocardial tissue, where they play a pivotal role in attenuating excessive inflammatory responses during myocardial ischemia/reperfusion (I/R) injury. Concurrently, soluble receptor for advanced glycation end-products (sRAGE) has been demonstrated to alleviate myocardial I/R injury by suppressing inflammation, suggesting a potential involvement of Tregs in the inhibitory effects of sRAGE on myocardial I/R injury. I/R surgery or glucose deprivation/reoxygenation was employed to explore myocardial injury and the related mechanisms by using cardiomyocyte-specific sRAGE knock-in mice or cultured cardiomyocytes. Potential molecular mechanisms were analyzed via western blotting, immunohistochemistry, and flow cytometric analysis. The findings revealed that sRAGE overexpression significantly increased the numbers of Tregs. Depletion of Tregs abrogated the protective effects of sRAGE against I/R-induced cardiac dysfunction, myocardial fibrosis, and inflammatory response in cardiac-specific sRAGE transgenic mice. Mechanistically, sRAGE was found to enhance the expression of programmed cell death ligand 1 (PD-L1) and its upstream JAK2/STAT3 signaling axis, thereby facilitating CD4+ T cells differentiation into Tregs within myocardial tissue during I/R. The study demonstrated that sRAGE protected against myocardial I/R injury by modulating the differentiation of Tregs through upregulation of the JAK2/STAT3-PD-L1 signaling pathway.

Although ticagrelor is recommended as opposed to clopidogrel in antiplatelet strategy for patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (pPCI), evidence is limited in patients with cardiogenic shock (CS). This study aims to evaluate the comparative efficacy and safety profile of ticagrelor and clopidogrel in patients with STEMI-CS undergoing pPCI. Using data from a nationwide, multicenter registry, eligible patients were stratified into clopidogrel or ticagrelor based on the choice of P2Y12 inhibitors within 24 h of first medical contact. Multivariable-adjusted Cox regression analyses, along with Cox models adjusted for propensity score matching and inverse probability treatment weighting were conducted to compare outcomes between ticagrelor and clopidogrel. The efficacy and safety outcomes were in-hospital all-cause mortality and major bleeding. Among 729 STEMI-CS patients in our cohort, 403 received clopidogrel and 326 received ticagrelor. Multivariable-adjusted Cox regression analyses showed that ticagrelor was not associated with a significant difference in all-cause mortality (adjusted HR: 1.04; 95

BACKGROUND:In 2012, the randomised trial IABP SHOCK II demonstrated that IABP did not reduce 30-day mortality in patients with acute myocardial infarction complicating cardiogenic shock (CS). However, SCAI proposed a new standardised classification of cardiogenic shock in 2019. It is reasonably hypothesised that the use of IABP may have different benefits for patients in different stages of CS. METHODS:AMI patients ≥18 years who had received treatment of implantation of IABP during emergency setting in Beijing Chaoyang Hospital between December 2010 and July 2021 were enrolled in this study. CS stages were classified at admission for all eligible cases. During the same period, AMI patients without implantation of IABP were matched with each stage of CS above using propensity score matching (PSM). Data were as follows: Stage B (n = 302), Stage C (n = 290), Stage D (n = 68), and Stage E (n = 32). In-hospital mortality was compared between using and without using IABP at each stage. RESULTS:In stage C, the in-hospital mortality was significantly lower in the IABP group (31/145, 21.4%) than in the group without IABP (47/145, 32.4%) (OR 0.567, 95% CI, p = .034). In-hospital mortality had no significant difference between use and no-use of IABP in stage B (16.6% vs 14.6%, p = .634), stage D (47.1% vs 38.2%, p = .462), and in stage E (81.3%vs 68.8%, p = .414). CONCLUSIONS:For patients with acute myocardial infarction complicating cardiogenic shock, IABP has no effect on in-hospital mortality in SCAI stages B, D, and E. However, in SCAI stage C, IABP can reduce in-hospital mortality.

12/15-Lipoxygenase (LOX) is a member of the LOX family that catalyzes the step from arachidonic acid to hydroxy-eicosatetraenoic acids (HETEs). Previous studies demonstrated that 12/15-LOX plays a critical role in the development of atherosclerosis, hypertension, heart failure, and other diseases; however, its role in myocardial ischemic injury was contraversal. Here, we investigated the inhibition of 12/15-LOX by baicalein on acute cardiac injury and dissected its molecular mechanism. In a mouse model of acute ischemia/reperfusion (I/R) injury, 12/15-LOX was significantly upregulated in the peri-infarct area surrounding the primary infarction. In cultured cardiac myocytes, baicalein suppressed apoptosis and caspase 3 activity in response to simulated ischemia/reperfusion (I/R). Moreover, administration of 12/15-LOX inhibitor, baicalein, significantly attenuated myocardial infarct size induced by I/R injury. Moreover, baicalein treatment significantly inhibited cardiomyocyte apoptosis, inflammatory responses and oxidative stress in the heart after I/R injury. The mechanisms underlying these effects were associated with the activation of ERK1/2 and AKT pathways and inhibition of activation of p38 MAPK, JNK1/2, and NF-kB/p65 pathways in the I/R-treated hearts and neonatal cardiomyoctes. Our data indicated that 12/15-LOX inhibitor baicalein can prevent myocardial I/R injury by modulation of multiple mechanisms, and suggest that baicalein could represent a novel therapeutic drug for acute myocardial infarction.

Metabolic dysfunction associated steatotic liver disease (MASLD) is a pressing global health issue with limited treatment options. Chinese sweet leaf tea (CSLT), rich in polyphenols, shows promise in addressing MASLD due to its anti-inflammatory, obesity-reducing, and metabolic-regulating properties. This study aimed to explore the therapeutic potential of CSLT polyphenols for MASLD treatment. A comprehensive approach combining bioinformatics, network pharmacology, molecular docking, high-throughput sequencing, and experimental validation was employed. CSLT extracts were screened for active compounds, and potential targets associated with MASLD were predicted. A protein-protein interaction network was constructed to identify key regulators of lipid metabolism. Molecular docking studies validated interactions between core polyphenols and MASLD-related targets. In vitro studies using HepG2 cells and in vivo studies in a high-fat diet-induced rat model were conducted to assess the efficacy of polyphenol-rich CSLT extract (PE-CSLT) in ameliorating MASLD symptoms. A total of Eighty-two chemical constituents were initially identified in CSLT. Twenty-six active compounds were screened in CSLT extracts, targeting one hundred and six proteins related to twenty MASLD-associated genes. PE-CSLT demonstrated significant efficacy in reducing body weight gain, serum lipid levels, and liver fat accumulation in MASLD rats. Gene expression analysis revealed modulation of key metabolic regulators, including SREBP1, ACACA, AMPK, and PPARα. Molecular docking confirmed strong binding of eleven PE-CSLT components to these targets. Our findings highlight the therapeutic potential of PE-CSLT for MASLD, providing a scientific basis for its development as a novel drug. This study underscores the promise of natural products in modern medicinal practices and emphasizes the need for further clinical evaluation of PE-CSLT in MASLD management.

BACKGROUND:Little is known about the risk factors and prognosis of new-onset atrial fibrillation (NOAF) in patients with primary percutaneous coronary intervention (PCI). OBJECTIVE:The purpose of this study was to assess the prevalence and prognosis of NOAF after PCI and the effects of anticoagulation on clinical outcomes. METHOD:Using data from the CCC-ACS (Improving Care for Cardiovascular Disease in China-Acute Coronary Syndrome) project, ST-elevation myocardial infarction (STEMI) patients undergoing PCI were stratified into 2 groups: with NOAF or without any atrial fibrillation. Multivariable logistic regression was used to identify NOAF predictors, and propensity-score matching estimated associations between NOAF and in-hospital outcomes. A meta-analysis was also performed by pooling our results with literature data. RESULTS:Of 19,288 STEMI patients undergoing PCI, 1.3% (n = 253) experienced NOAF. Independent risk factors were age ≥65 years, history of hypertension, stroke, heart failure, Killip class IV, and right coronary artery as the culprit artery. NOAF was associated with a higher risk of all-cause mortality (hazard ratio [HR] 2.26, 95% confidence interval [CI] 1.08-4.71), heart failure (HR 4.29, 95% CI 2.81-6.55), cardiogenic shock (HR 4.30, 95% CI 2.28-8.13), in-stent thrombosis (HR 6.04, 95% CI 1.71-21.45), and major bleeding (HR 2.86, 95% CI 1.44-5.66) during hospitalization. Meta-analysis found that NOAF had a higher risk of in-hospital stroke (odds ratio 3.33, 95% CI 1.73-6.43). In-hospital use of anticoagulants was associated with lower rates of all-cause mortality but similar rates of major bleeding in NOAF patients. CONCLUSION:Our study suggests NOAF following PCI is uncommon but associated with poor in-hospital prognosis. Findings support the use of anticoagulants in these patients during hospitalization.

BACKGROUND:Although ticagrelor is recommended as opposed to clopidogrel in antiplatelet strategy for patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (pPCI), evidence is limited in patients with cardiogenic shock (CS). OBJECTIVE:This study aims to evaluate the comparative efficacy and safety profile of ticagrelor and clopidogrel in patients with STEMI-CS undergoing pPCI. METHODS:Using data from a nationwide, multicenter registry, eligible patients were stratified into clopidogrel or ticagrelor based on the choice of P2Y12 inhibitors within 24 h of first medical contact. Multivariable-adjusted Cox regression analyses, along with Cox models adjusted for propensity score matching and inverse probability treatment weighting were conducted to compare outcomes between ticagrelor and clopidogrel. The efficacy and safety outcomes were in-hospital all-cause mortality and major bleeding. RESULTS:Among 729 STEMI-CS patients in our cohort, 403 received clopidogrel and 326 received ticagrelor. Multivariable-adjusted Cox regression analyses showed that ticagrelor was not associated with a significant difference in all-cause mortality (adjusted HR: 1.04; 95% CI: 0.69-1.56; p = 0.840) and major bleeding (adjusted HR: 1.30; 95% CI: 0.62-2.76; p = 0.489) compared to clopidogrel. Consistent results were found in the analyses adjusted by propensity score matching and inverse probability of treatment weighting. CONCLUSIONS:Our findings suggest that the choice of either ticagrelor or clopidogrel was feasible as a P2Y12 inhibitor for dual anti-platelet strategy in STEMI-CS patients undergoing pPCI, as no significant difference between these two agents was observed in all-cause mortality and major bleeding during hospitalization. TRIAL REGISTRATION:ClinicalTrials.gov, NCT02306616. Registered 29 November 2014.

Glomerular basement membrane (GBM) thickening, the earliest morphological change of diabetic nephropathy (DN), is related to glomerular endothelial cells (GECs) dysfunction which increase extracellular matrix (ECM) synthesizing. Apelin, the endogenous ligand for apelin/apelin receptor (APJ), is reported to alleviate endothelial cell dysfunction in DN. Therefore, it was hypothesized that apelin/APJ reduced GBM thickening by decreasing the synthesis of ECM in GECs. The results showed that apelin reduced glomerular fibrosis and GBM thickening by decreasing the expression of laminin and collagen IV in diabetic mice, which were cancelled following APJ knockout in GECs. Furthermore, apelin/APJ inhibited the synthesis of laminin and collagen IV in GECs by increasing the expression and activity of SIRT3, which promoted KLF15 deacetylation and translocation into nucleus. In conclusion, apelin/APJ reduced GBM thickening in diabetes mellitus by preventing laminin and collagen IV synthesizing via SIRT3‑KLF15 pathway in GECs.

Background:The real-world effectiveness of Nirmatrelvir/ritonavir (NMV/RTV) against the SARS-CoV-2 Omicron variant in older patients remains uncertain. We aimed to estimate the effectiveness in older patients aged 80 and above with severe COVID-19. Methods:A retrospective study analyzed 263 COVID-19 patients aged 80 and above, admitted to the Department of Geriatrics at Jinling Hospital, affiliated with Nanjing University, between December 15, 2022, and January 15, 2023. Among them, 136 cases were non-severe, and 127 were severe. The severe cases were further categorized into a survival group (n=74) and a death group (n=53) based on 28-day mortality. Kaplan-Meier survival curves assessed 28-day survival, and Cox regression models identified factors influencing survival. Results:Among the 127 severe cases, the death group had significantly higher rates of stroke history, renal impairment, endotracheal intubation, renal replacement therapy (RRT), bacterial infection, but significantly lower rates of NMV/RTV use and anticoagulation (p<0.05). Kaplan-Meier analysis indicated that NMV/RTV improved 28-day survival in severe older COVID-19 patients. Multivariate Cox regression identified NMV/RTV as a protective factor (adjusted hazard ratio [HR] 0.307, 95% confidence interval [CI] 0.152-0.620, p=0.001), while COPD (adjusted HR 2.993, 95% CI 1.563-5.731, p=0.001), stroke history (adjusted HR 3.871, 95% CI 1.953-7.671, p<0.001), and endotracheal intubation (adjusted HR 5.058, 95% CI 2.809-9.108, p<0.001) were significant risk factors for increased 28-day mortality. Conclusion:NMV/RTV may improve the 28-day survival rate of older patients aged 80 and above with severe COVID-19.

Cardiogenic shock (CS) is a lethal complication of ST-elevation myocardial infarction (STEMI). The impact of post-procedure anticoagulants (PPAC) in STEMI-CS patients undergoing primary percutaneous coronary intervention (PPCI) remains unknown. In the Improving Care for Cardiovascular Disease in China-Acute Coronary Syndrome registry (2014–2019), STEMI patients with CS on admission undergoing PPCI were stratified into two groups based on the use of PPAC or not. The primary outcome was all-cause mortality during hospitalization. Other outcomes including major bleeding were also investigated. Of 36,873 patients with STEMI, 855 eligible patients with CS undergoing PPCI were included in our study, among which 614 patients were treated by PPAC and 241 were not. Adjusted by multi-variable Cox regression, PPAC was associated with a lower risk of in-hospital all-cause mortality (14.9

Podocytes are essential to maintain the normal filtration function of glomerular basement membrane, which could be injured by ischemia-reperfusion. As complicated function of autophagy in terminal differentiated podocytes, autophagy dysfunction might contribute to I/R induced renal dysfunction following glomerular filtration membrane (GFM) injuries. Meanwhile, apelin-13, an endogenous polypeptide, has been proved to be effective in regulating autophagy and apoptosis in podocytes. Therefore, it is hypothesized that apelin-13 may protect podocytes from IRI by inhibiting podocyte apoptosis through regulation of podocyte autophagy. Our study demonstrates for that podocytes are also involved in renal ischemia-reperfusion (I/R) injury and shows in detail the morphological and functional changes in podocytes during renal I/R. Because podocytes are terminally differentiated cells whose homeostasis require high levels of autophagy, we investigate the cellular mechanisms underlying the effects of apelin-13 on I/R-mediated podocyte injury in terms of autophagy. In addition, our study demonstrates that apelin-13 ameliorates renal I/R injury in podocyte injury, by increasing podocyte autophagy through inhibition of m-TOR phosphorylation, which in turn inhibits apoptosis.

Organophosphorus compounds have long been considered valuable in both organic synthesis and life science. P(III)-nucleophiles, such as phosphites, phosphonites, and diaryl/alkyl phosphines, are particularly noteworthy as phosphorylation reagents for their ability to form new P-C bonds, producing more stable, ecofriendly, and cost-effective organophosphorus compounds. These nucleophiles follow similar phosphorylation routes as in the functionalization of P-H bonds and P-OH bonds. Activation can occur through photocatalytic, electrocatalytic, or thermo-driven reactions, often in coordination with a Michaelis-Arbuzov-trpe rearrangement process, to produce the desired products. As such, this review offers a thorough overview of the phosphorylated transformation and potential mechanisms of P(III)-nucleophiles, specifically focusing on developments since 2010. Notably, this review may provide researchers with valuable insights into designing and synthesizing functionalized organophosphorus compounds from P(III)-nucleophiles, guiding future advancements in both research and practical applications.