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Neural networks demonstrate vulnerability to small, non-random perturbations, emerging as adversarial attacks. Such attacks, born from the gradient of the loss function relative to the input, are discerned as input conjugates, revealing a systemic fragility within the network structure. Intriguingly, a mathematical congruence manifests between this mechanism and the quantum physics' uncertainty principle, casting light on a hitherto unanticipated interdisciplinarity. This inherent susceptibility within neural network systems is generally intrinsic, highlighting not only the innate vulnerability of these networks, but also suggesting potential advancements in the interdisciplinary area for understanding these black-box networks.
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Ferroelectric materials, traditionally comprising inorganic ceramics and polymers, are commonly used in medical implantable devices. However, their nondegradable nature often necessitates secondary surgeries for removal. In contrast, ferroelectric molecular crystals have the advantages of easy solution processing, lightweight, and good biocompatibility, which are promising candidates for transient (short-term) implantable devices. Despite these benefits, the discovered biodegradable ferroelectric materials remain limited due to the absence of efficient design strategies. Here, inspired by the polar structure of polyvinylidene fluoride (PVDF), a ferroelectric molecular crystal 1H,1H,9H,9H-perfluoro-1,9-nonanediol (PFND), which undergoes a cubic-to-monoclinic ferroelectric plastic phase transition at 339 K, is discovered. This transition is facilitated by a 2D hydrogen bond network formed through O-H···O interactions among the oriented PFND molecules, which is crucial for the manifestation of ferroelectric properties. In this sense, by reducing the number of -CF2- groups from ≈5 000 in PVDF to seven in PFND, it is demonstrated that this ferroelectric compound only needs simple solution processing while maintaining excellent biosafety, biocompatibility, and biodegradability. This work illuminates the path toward the development of new biodegradable ferroelectric molecular crystals, offering promising avenues for biomedical applications.
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Non-small cell lung cancer (NSCLC) remains the leading cause of cancer-related deaths. With the development of screening, patient selection and treatment strategies, patients' survival outcomes and living quality significantly improved. However, some patients still have local recurrence or residual tumors after receiving definitive therapies. Salvage surgery has been regarded as an effective option for recurrent or residual NSCLC, but its effectiveness remains undetermined. Furthermore, conversion surgery is a special type of salvage surgery for tumors converted from "initially unresectable" to "potentially resectable" status due to a favorable response to systemic treatments. Although conversion surgery is a promising curative procedure for advanced NSCLC, its concept and clinical value remain unfamiliar to clinicians. In this narrative review, we provided an overview of the safety and efficacy of salvage surgery, especially salvage surgery after sublobar resection in early-stage NSCLC. More importantly, we highlighted the concept and value of conversion surgery after systemic treatment in advanced NSCLC to gain some insights into its role in the treatment of lung cancer.
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RATIONALE: Desmoid tumor (DT) is a rare soft tissue tumor that can occur anywhere in the body. Abdominal wall DT presents unique clinical challenges due to its distinctive manifestations, treatment modalities, and the lack of biomarkers for diagnosis and recurrence prediction, making clinical decisions exceedingly complex. PATIENT CONCERNS: A 32-year-old female who underwent radical resection combined with patch reinforcement for rectus abdominis DT, successfully alleviating abdominal discomfort, with no recurrence during the 6-month follow-up after surgery. DIAGNOSES: Based on the imaging studies and medical history, the patient underwent radical surgical resection. Histopathology reveals that the tumor cells predominantly composed of proliferative fibroblasts with local collagen deposition. The lesional cells show positive staining for ß-catenin, indicating a diagnosis of DT. INTERVENTIONS: The patient underwent radical surgical resection with patch reinforcement to repair the abdominal wall defect. Pathology confirmed negative margins, achieving an R0 resection, and genetic testing identified a T41A mutation in CTNNB1. Consequently, no additional adjuvant therapy was administered postoperatively. OUTCOMES: The patient was discharged with the incision healing well after 3 days postoperation. Upon reexamination 6 months later, no recurrence or adverse complications were observed. LESSONS: Abdominal wall DT treatment requires personalized plans from multidisciplinary team discussions. Genetic testing plays a crucial role in identifying novel biomarkers for abdominal wall DT. We have once again demonstrated the significant clinical significance of CTNNB1 mutations in the diagnosis and progression of abdominal wall DT. Additionally, genes such as CCND1, CYP3A4, SLIT1, RRM1, STIM1, ESR2, UGT1A1, among others, may also be closely associated with the progression of abdominal wall DT. Future research should delve deeper into and systematically evaluate the precise impact of these genetic mutations on treatment selection and prognosis for abdominal wall DT, in order to better guide patient management and treatment decisions.
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Fibromatosis Agresiva , Recto del Abdomen , Humanos , Femenino , Adulto , Fibromatosis Agresiva/cirugía , Fibromatosis Agresiva/diagnóstico , Fibromatosis Agresiva/genética , Fibromatosis Agresiva/patología , Recto del Abdomen/cirugía , beta Catenina/genética , Neoplasias Abdominales/cirugía , Neoplasias Abdominales/genética , Neoplasias Abdominales/diagnóstico , Neoplasias Abdominales/patologíaRESUMEN
BACKGROUND: It is currently uncertain whether the combination of a proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor and high-intensity statin treatment can effectively reduce cardiovascular events in patients with acute coronary syndrome (ACS) who have undergone percutaneous coronary intervention (PCI) for culprit lesions. METHODS: This study protocol describes a double-blind, randomized, placebo-controlled, multicenter study aiming to investigate the efficacy and safety of combining a PCSK9 inhibitor with high-intensity statin therapy in patients with ACS following PCI. A total of 1212 patients with ACS and multiple lesions will be enrolled and randomly assigned to receive either PCSK9 inhibitor plus high-intensity statin therapy or high-intensity statin monotherapy. The randomization process will be stratified by sites, diabetes, initial presentation and use of stable (≥4 weeks) statin treatment at presentation. PCSK 9 inhibitor or its placebo is injected within 4 hours after PCI for the culprit lesion. The primary endpoint is the composite of cardiovascular death, myocardial infarction, stroke, re-hospitalization due to ACS or heart failure, or any ischemia-driven coronary revascularization at one-year follow-up between two groups. Safety endpoints mean PCSK 9 inhibitor and statin intolerance. CONCLUSION: The SHAWN study has been specifically designed to evaluate the effectiveness and safety of adding a PCSK9 inhibitor to high-intensity statin therapy in patients who have experienced ACS following PCI. The primary objective of this study is to generate new evidence regarding the potential benefits of combining a PCSK9 inhibitor with high-intensity statin treatment in reducing cardiovascular events among these patients.
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BACKGROUND: Drug-coated balloon (DCB) angioplasty seems a safe and effective option for specific de novo coronary lesions. However, the beneficial effect of intravascular ultrasound (IVUS)-guided DCB angioplasty in de novo lesions remains uncertain. OBJECTIVES: This study aimed to assess the benefits of IVUS guidance over angiography guidance during DCB angioplasty in de novo coronary lesions. METHODS: A total of 260 patients with high bleeding risk who had a de novo coronary lesion (reference vessel diameter 2.0-4.0 mm, and lesion length ≤15 mm) were randomly assigned to either an IVUS-guided or an angioplasty-guided DCB angioplasty group. The primary endpoint was in-segment late lumen loss (LLL) at 7 months after procedure. The secondary endpoint was target vessel failure at 6 months. RESULTS: A total of 2 patients in the angiography-guided group and 7 patients in the IVUS-guided group underwent bailout stent implantation (P = 0.172). The primary endpoint of 7-month LLL was 0.03 ± 0.52 mm with angiography guidance vs -0.10 ± 0.34 mm with IVUS guidance (mean difference 0.14 mm; 95% CI: 0.02-0.26; P = 0.025). IVUS guidance was also associated with a larger 7-month minimal lumen diameter (2.06 ± 0.62 mm vs 1.75 ± 0.63 mm; P < 0.001) and a smaller diameter stenosis (28.15% ± 13.88% vs 35.83% ± 17.69%; P = 0.001) compared with angiography guidance. Five target vessel failures occurred at 6 months, with 4 (3.1%) in the angiography-guided group and 1 (0.8%) in the IVUS-guided group (P = 0.370). CONCLUSIONS: This study demonstrated that IVUS-guided DCB angioplasty is associated with a lower LLL in patients with a de novo coronary lesion compared with angiography guidance. (Intravascular Ultrasound Versus Angiography Guided Drug-Coated Balloon [ULTIMATE-III]; NCT04255043).
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Angioplastia Coronaria con Balón , Catéteres Cardíacos , Fármacos Cardiovasculares , Materiales Biocompatibles Revestidos , Angiografía Coronaria , Enfermedad de la Arteria Coronaria , Valor Predictivo de las Pruebas , Ultrasonografía Intervencional , Humanos , Masculino , Femenino , Persona de Mediana Edad , Anciano , Angioplastia Coronaria con Balón/instrumentación , Angioplastia Coronaria con Balón/efectos adversos , Resultado del Tratamiento , Factores de Tiempo , Enfermedad de la Arteria Coronaria/terapia , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Fármacos Cardiovasculares/administración & dosificación , Fármacos Cardiovasculares/efectos adversos , Estudios Prospectivos , Factores de Riesgo , ChinaRESUMEN
BACKGROUND: Lymph node metastasis is significantly associated with a worse prognosis in patients with localized early-stage esophageal squamous cell carcinoma. This study aimed to explore the prognostic factors and develop a nomogram for predicting survival in patients with pathologic T1-2N+ esophageal squamous cell carcinoma. METHODS: Between 2014 and 2022, patients with pT1-2N+ esophageal squamous cell carcinoma who underwent esophagectomy with lymphadenectomy at 2 institutes were reviewed and assigned to training and external validation cohorts. Independent prognostic factors were identified via univariate and multivariate Cox regression analyses. The nomogram model was developed and evaluated by the area under the receiver operating characteristic curve and calibration curve. RESULTS: In total, 268 patients with a median age of 65 years (range, 40-82) were included and assigned to training (n = 190) and external validation (n = 78) cohorts. The Cox proportional hazards model demonstrated that body mass index (P = .031), surgical approach (P < .001), T stage (P = .015), and Clavien-Dindo classification (P < .001) were independent prognostic factors in the training cohort. The nomogram showed good discrimination, with an area under the receiver operating characteristic curve for 1-year, 3-year, and 5-year of 0.810, 0.789, and 0.809 in the training cohort and 0.782, 0.679, and 0.698 in the validation cohort. The calibration curve showed that the predicted survival probability was in good agreement with the actual survival probability. CONCLUSION: Lower body mass index, left surgical approach, T2 stage, and Clavien-Dindo classification grade III to V were related to worse prognosis in patients with pT1-T2N+ esophageal squamous cell carcinoma. The developed nomogram may predict individual survival accurately.
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Neoplasias Esofágicas , Carcinoma de Células Escamosas de Esófago , Esofagectomía , Estadificación de Neoplasias , Nomogramas , Humanos , Persona de Mediana Edad , Masculino , Femenino , Estudios Retrospectivos , Anciano , Carcinoma de Células Escamosas de Esófago/cirugía , Carcinoma de Células Escamosas de Esófago/mortalidad , Carcinoma de Células Escamosas de Esófago/patología , Neoplasias Esofágicas/mortalidad , Neoplasias Esofágicas/patología , Neoplasias Esofágicas/cirugía , Pronóstico , Adulto , Anciano de 80 o más Años , Metástasis Linfática , Escisión del Ganglio Linfático , Curva ROC , Modelos de Riesgos ProporcionalesRESUMEN
Importance: The associations between angiographic findings and post-percutaneous coronary intervention (PCI) fractional flow reserve (FFR) and their clinical relevance according to residual functional disease burden have not been thoroughly investigated. Objectives: To evaluate the association of angiographic and physiologic parameters according to residual functional disease burden after drug-eluting stent implantation. Design, Setting, and Participants: This cohort study population was from the International Post-PCI FFR registry, which incorporated 4 registries from Korea, China, and Japan. Patients who underwent angiographically successful second-generation drug-eluting stent implantation and post-PCI FFR measurement were included in the analysis. The patients were divided into 3 groups according to the residual disease burden (post-PCI FFR ≤0.80 [residual ischemia], 0.81-0.86 [suboptimal], and >0.86 [optimal]). The data were collected from August 23, 2018, to June 11, 2019, and the current analysis was performed from January 11, 2022, to October 7, 2023. Exposures: Angiographic parameters and post-PCI FFR. Main Outcomes and Measures: The primary outcome was target vessel failure (TVF), defined as a composite of cardiac death, target vessel-related myocardial infarction, and target vessel revascularization (TVR) at 2 years. Results: In this cohort of 2147 patients, the mean (SD) age was 64.3 (10.0) years, and 1644 patients (76.6%) were men. Based on the post-PCI physiologic status, 269 patients (12.5%) had residual ischemia, 551 (25.7%) had suboptimal results, and 1327 (61.8%) had optimal results. Angiographic parameters had poor correlations with post-PCI FFR (r < 0.20). Post-PCI FFR was isolated from all angiographic parameters in the unsupervised hierarchical cluster analysis. Post-PCI FFR was associated with the occurrence of TVF (adjusted hazard ratio [AHR] per post-PCI FFR 0.01 increase, 0.94 [95% CI, 0.92-0.97]; P < .001), but angiographic parameters were not. The residual ischemia group had a significantly higher rate of TVF than the suboptimal group (AHR, 1.75 [95% CI, 1.08-2.83]; P = .02) and the optimal group (AHR, 2.94 [95% CI, 1.82-4.73]; P < .001). The TVR in the residual ischemia group was predominantly associated with TVR in the nonstented segment (14 [53.8%]), unlike the other 2 groups (3 [10.0%] in the suboptimal group and 13 [30.2%] in the optimal group). Conclusions and Relevance: In this cohort study of the International Post-PCI FFR registry, a low degree of associations were observed between angiographic and physiologic parameters after PCI. Post-PCI FFR, unlike angiographic parameters, was associated with clinical events and the distribution of clinical events. The current study supports the use of post-PCI FFR as a procedural quality metric and further prospective study is warranted.
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Angiografía Coronaria , Reserva del Flujo Fraccional Miocárdico , Intervención Coronaria Percutánea , Humanos , Reserva del Flujo Fraccional Miocárdico/fisiología , Intervención Coronaria Percutánea/métodos , Masculino , Femenino , Persona de Mediana Edad , Anciano , Enfermedad de la Arteria Coronaria/fisiopatología , Enfermedad de la Arteria Coronaria/cirugía , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Sistema de Registros , Stents Liberadores de Fármacos , Estudios de Cohortes , República de Corea , China/epidemiología , Resultado del TratamientoRESUMEN
Calcified aortic stenosis (AS) is one of the most common valvular heart diseases worldwide, characterized by progressive fibrocalcific remodeling and thickening of the leaflets, which ultimately leads to obstruction of blood flow. Its pathobiology is an active and complicated process, involving endothelial cell dysfunction, lipoprotein deposition and oxidation, chronic inflammation, phenotypic transformation of valve interstitial cells, neovascularization, and intravalvular hemorrhage. To date, no targeted drug has been proven to slow down or prevent disease progression. Aortic valve replacement is still the optimal treatment of AS. This article reviews the etiology, diagnosis, and management of calcified aortic stenosis and proposes novel potential therapeutic targets.
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Estenosis de la Válvula Aórtica , Válvula Aórtica , Calcinosis , Humanos , Estenosis de la Válvula Aórtica/cirugía , Estenosis de la Válvula Aórtica/fisiopatología , Calcinosis/terapia , Válvula Aórtica/patología , Válvula Aórtica/cirugía , Implantación de Prótesis de Válvulas Cardíacas/métodosRESUMEN
The decrease in eggshell quality seriously affects production efficiency. Guinea fowl (GF) eggs possess strong eggshells because of their unique crystal structure, and few systematic studies have compared laying hen and GF eggs. Sixty eggs were collected from both 40-week-old Dwarf Layer-White (DWL-White) laying hens and GF, and the eggshell quality, ultrastructure, bubble pores, and composition were measured. The results showed that the DWL-White eggs had a higher egg weight and a lower eggshell strength, strength per unit weight, thickness, and ratio than the GF eggs (p < 0.01). There were differences in the mammillary layer thickness ratio, the effective layer thickness ratio, the quantity of bubble pores (QBPs), the ratio of the sum of the area of bubble pores to the area of the eggshell in each image (ARBE), and the average area of bubble pores (AABPs) between the DWL-White and GF eggs (p < 0.01). The composition analysis demonstrated that there were differences in the organic matter, inorganic matter, calcium, and phosphorus between the DWL-White and GF eggs (p < 0.01). There were positive associations between the mammillary knob number in the image and the QBPs and ARBE and a negative correlation with the AABPs in the DWL-White eggs (p < 0.01). This study observed distinctions that offer new insights into enhancing eggshell quality.
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[This corrects the article DOI: 10.3389/fmicb.2020.591478.].
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BACKGROUND: Following percutaneous coronary intervention with stent placement to treat acute coronary syndromes, international clinical guidelines generally recommend dual antiplatelet therapy with aspirin plus a P2Y12 receptor inhibitor for 12 months to prevent myocardial infarction and stent thrombosis. However, data on single antiplatelet therapy with a potent P2Y12 inhibitor earlier than 12 months after percutaneous coronary intervention for patients with an acute coronary syndrome are scarce. The aim of this trial was to assess whether the use of ticagrelor alone, compared with ticagrelor plus aspirin, could reduce the incidence of clinically relevant bleeding events without an accompanying increase in major adverse cardiovascular or cerebrovascular events (MACCE). METHODS: In this randomised, placebo-controlled, double-blind clinical trial, patients aged 18 years or older with an acute coronary syndrome who completed the IVUS-ACS study and who had no major ischaemic or bleeding events after 1-month treatment with dual antiplatelet therapy were randomly assigned to receive oral ticagrelor (90 mg twice daily) plus oral aspirin (100 mg once daily) or oral ticagrelor (90 mg twice daily) plus a matching oral placebo, beginning 1 month and ending at 12 months after percutaneous coronary intervention (11 months in total). Recruitment took place at 58 centres in China, Italy, Pakistan, and the UK. Patients were required to remain event-free for 1 month on dual antiplatelet therapy following percutaneous coronary intervention with contemporary drug-eluting stents. Randomisation was done using a web-based system, stratified by acute coronary syndrome type, diabetes, IVUS-ACS randomisation, and site, using dynamic minimisation. The primary superiority endpoint was clinically relevant bleeding (Bleeding Academic Research Consortium [known as BARC] types 2, 3, or 5). The primary non-inferiority endpoint was MACCE (defined as the composite of cardiac death, myocardial infarction, ischaemic stroke, definite stent thrombosis, or clinically driven target vessel revascularisation), with an expected event rate of 6·2% in the ticagrelor plus aspirin group and an absolute non-inferiority margin of 2·5 percentage points between 1 month and 12 months after percutaneous coronary intervention. The two co-primary endpoints were tested sequentially; the primary superiority endpoint had to be met for hypothesis testing of the MACCE outcome to proceed. All principal analyses were assessed in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, NCT03971500, and is completed. FINDINGS: Between Sept 21, 2019, and Oct 27, 2022, 3400 (97·0%) of the 3505 participants in the IVUS-ACS study were randomly assigned (1700 patients to ticagrelor plus aspirin and 1700 patients to ticagrelor plus placebo). 12-month follow-up was completed by 3399 (>99·9%) patients. Between month 1 and month 12 after percutaneous coronary intervention, clinically relevant bleeding occurred in 35 patients (2·1%) in the ticagrelor plus placebo group and in 78 patients (4·6%) in the ticagrelor plus aspirin group (hazard ratio [HR] 0·45 [95% CI 0·30 to 0·66]; p<0·0001). MACCE occurred in 61 patients (3·6%) in the ticagrelor plus placebo group and in 63 patients (3·7%) in the ticagrelor plus aspirin group (absolute difference -0·1% [95% CI -1·4% to 1·2%]; HR 0·98 [95% CI 0·69 to 1·39]; pnon-inferiority<0·0001, psuperiority=0·89). INTERPRETATION: In patients with an acute coronary syndrome who had percutaneous coronary intervention with contemporary drug-eluting stents and remained event-free for 1 month on dual antiplatelet therapy, treatment with ticagrelor alone between month 1 and month 12 after the intervention resulted in a lower rate of clinically relevant bleeding and a similar rate of MACCE compared with ticagrelor plus aspirin. Along with the results from previous studies, these findings show that most patients in this population can benefit from superior clinical outcomes with aspirin discontinuation and maintenance on ticagrelor monotherapy after 1 month of dual antiplatelet therapy. FUNDING: The Chinese Society of Cardiology, the National Natural Scientific Foundation of China, and the Jiangsu Provincial & Nanjing Municipal Clinical Trial Project. TRANSLATION: For the Mandarin translation of the abstract see Supplementary Materials section.
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Síndrome Coronario Agudo , Aspirina , Quimioterapia Combinada , Hemorragia , Intervención Coronaria Percutánea , Inhibidores de Agregación Plaquetaria , Ticagrelor , Humanos , Ticagrelor/uso terapéutico , Aspirina/uso terapéutico , Aspirina/administración & dosificación , Intervención Coronaria Percutánea/métodos , Síndrome Coronario Agudo/terapia , Método Doble Ciego , Masculino , Femenino , Persona de Mediana Edad , Inhibidores de Agregación Plaquetaria/uso terapéutico , Anciano , Hemorragia/inducido químicamente , Antagonistas del Receptor Purinérgico P2Y/uso terapéutico , Antagonistas del Receptor Purinérgico P2Y/administración & dosificación , Terapia Antiplaquetaria Doble/métodos , Resultado del TratamientoRESUMEN
BACKGROUND: Intravascular ultrasound-guided percutaneous coronary intervention has been shown to result in superior clinical outcomes compared with angiography-guided percutaneous coronary intervention. However, insufficient data are available concerning the advantages of intravascular ultrasound guidance for patients with an acute coronary syndrome. This trial aimed to investigate whether the use of intravascular ultrasound guidance, as compared with angiography guidance, improves the outcomes of percutaneous coronary intervention with contemporary drug-eluting stents in patients presenting with an acute coronary syndrome. METHODS: In this two-stage, multicentre, randomised trial, patients aged 18 years or older and presenting with an acute coronary syndrome at 58 centres in China, Italy, Pakistan, and the UK were randomly assigned to intravascular ultrasound-guided percutaneous coronary intervention or angiography-guided percutaneous coronary intervention. Patients, follow-up health-care providers, and assessors were masked to random assignment; however, staff in the catheterisation laboratory were not. The primary endpoint was target vessel failure, a composite of cardiac death, target vessel myocardial infarction, or clinically driven target vessel revascularisation at 1 year after randomisation. This trial is registered at ClinicalTrials.gov, NCT03971500, and is completed. FINDINGS: Between Aug 20, 2019 and Oct 27, 2022, 3505 patients with an acute coronary syndrome were randomly assigned to intravascular ultrasound-guided percutaneous coronary intervention (n=1753) or angiography-guided percutaneous coronary intervention (n=1752). 1-year follow-up was completed in 3504 (>99·9%) patients. The primary endpoint occurred in 70 patients in the intravascular ultrasound group and 128 patients in the angiography group (Kaplan-Meier rate 4·0% vs 7·3%; hazard ratio 0·55 [95% CI 0·41-0·74]; p=0·0001), driven by reductions in target vessel myocardial infarction or target vessel revascularisation. There were no significant differences in all-cause death or stent thrombosis between groups. Safety endpoints were also similar in the two groups. INTERPRETATION: In patients with an acute coronary syndrome, intravascular ultrasound-guided implantation of contemporary drug-eluting stents resulted in a lower 1-year rate of the composite outcome of cardiac death, target vessel myocardial infarction, or clinically driven revascularisation compared with angiography guidance alone. FUNDING: The Chinese Society of Cardiology, the National Natural Scientific Foundation of China, and Jiangsu Provincial & Nanjing Municipal Clinical Trial Project. TRANSLATION: For the Mandarin translation of the abstract see Supplementary Materials section.
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Síndrome Coronario Agudo , Angiografía Coronaria , Stents Liberadores de Fármacos , Intervención Coronaria Percutánea , Ultrasonografía Intervencional , Humanos , Síndrome Coronario Agudo/terapia , Síndrome Coronario Agudo/diagnóstico por imagen , Síndrome Coronario Agudo/cirugía , Intervención Coronaria Percutánea/métodos , Ultrasonografía Intervencional/métodos , Femenino , Masculino , Persona de Mediana Edad , Angiografía Coronaria/métodos , Anciano , Resultado del Tratamiento , ChinaRESUMEN
STUDY OBJECTIVE: To assess the impact of preoperative infection with the contemporary strain of severe acute respiratory coronavirus 2 (SARS-CoV-2) on postoperative mortality, respiratory morbidity and extrapulmonary complications after elective, noncardiac surgery. DESIGN: An ambidirectional observational cohort study. SETTING: A tertiary and teaching hospital in Shanghai, China. PATIENTS: All adult patients (≥ 18 years of age) who underwent elective, noncardiac surgery under general anesthesia at Huashan Hospital of Fudan University from January until March 2023 were screened for eligibility. A total of 2907 patients were included. EXPOSURE: Preoperative coronavirus disease 2019 (COVID-19) positivity. MEASUREMENTS: The primary outcome was 30-day postoperative mortality. The secondary outcomes included postoperative pulmonary complications (PPCs), myocardial injury after noncardiac surgery (MINS), acute kidney injury (AKI), postoperative delirium (POD) and postoperative sleep quality. Multivariable logistic regression was used to assess the risk of postoperative mortality and morbidity imposed by preoperative COVID-19. MAIN RESULTS: The risk of 30-day postoperative mortality was not associated with preoperative COVID-19 [adjusted odds ratio (aOR), 95% confidence interval (CI): 0.40, 0.13-1.28, P = 0.123] or operation timing relative to diagnosis. Preoperative COVID-19 did not increase the risk of PPCs (aOR, 95% CI: 0.99, 0.71-1.38, P = 0.944), MINS (aOR, 95% CI: 0.54, 0.22-1.30; P = 0.168), or AKI (aOR, 95% CI: 0.34, 0.10-1.09; P = 0.070) or affect postoperative sleep quality. Patients who underwent surgery within 7 weeks after COVID-19 had increased odds of developing delirium (aOR, 95% CI: 2.26, 1.05-4.86, P = 0.036). CONCLUSIONS: Preoperative COVID-19 or timing of surgery relative to diagnosis did not confer any added risk of 30-day postoperative mortality, PPCs, MINS or AKI. However, recent COVID-19 increased the risk of POD. Perioperative brain health should be considered during preoperative risk assessment for COVID-19 survivors.
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COVID-19 , Procedimientos Quirúrgicos Electivos , Complicaciones Posoperatorias , Humanos , COVID-19/mortalidad , COVID-19/epidemiología , COVID-19/complicaciones , Femenino , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/mortalidad , Procedimientos Quirúrgicos Electivos/efectos adversos , Anciano , China/epidemiología , Estudios de Cohortes , Adulto , Factores de Riesgo , Periodo PreoperatorioRESUMEN
BACKGROUND: Noninvasively and accurately predicting subcarinal lymph node metastasis (SLNM) for patients with non-small cell lung cancer (NSCLC) remains challenging. This study was designed to develop and validate a tumor and subcarinal lymph nodes (tumor-SLNs) dual-region computed tomography (CT) radiomics model for predicting SLNM in NSCLC. METHODS: This retrospective study included NSCLC patients who underwent lung resection and SLNs dissection between January 2017 and December 2020. The radiomic features of the tumor and SLNs were extracted from preoperative CT, respectively. Ninety machine learning (ML) models were developed based on tumor region, SLNs region, and tumor-SLNs dual-region. The model performance was assessed by the area under the curve (AUC) and validated internally by fivefold cross-validation. RESULTS: In total, 202 patients were included in this study. ML models based on dual-region radiomics showed good performance for SLNM prediction, with a median AUC of 0.794 (range, 0.686-0.880), which was superior to those of models based on tumor region (median AUC, 0.746; range, 0.630-0.811) and SLNs region (median AUC, 0.700; range, 0.610-0.842). The ML model, which is developed by using the naive Bayes algorithm and dual-region features, had the highest AUC of 0.880 (range of cross-validation, 0.825-0.937) among all ML models. The optimal logistic regression model was inferior to the optimal ML model for predicting SLNM, with an AUC of 0.727. CONCLUSIONS: The CT radiomics showed the potential for accurately predicting SLNM in NSCLC patients. The ML model with dual-region radiomic features has better performance than the logistic regression or single-region models.
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Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Metástasis Linfática , Aprendizaje Automático , Tomografía Computarizada por Rayos X , Humanos , Carcinoma de Pulmón de Células no Pequeñas/diagnóstico por imagen , Carcinoma de Pulmón de Células no Pequeñas/patología , Carcinoma de Pulmón de Células no Pequeñas/cirugía , Carcinoma de Pulmón de Células no Pequeñas/secundario , Neoplasias Pulmonares/diagnóstico por imagen , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/cirugía , Masculino , Femenino , Estudios Retrospectivos , Tomografía Computarizada por Rayos X/métodos , Persona de Mediana Edad , Anciano , Estudios de Seguimiento , Pronóstico , Adulto , Ganglios Linfáticos/patología , Ganglios Linfáticos/diagnóstico por imagen , Ganglios Linfáticos/cirugía , Anciano de 80 o más Años , Escisión del Ganglio Linfático , Neumonectomía , RadiómicaRESUMEN
BACKGROUND: Previous studies primarily demonstrated that transfemoral transcatheter aortic valve replacement (TAVR) with self-expanding valve appeared to be a safe and feasible treatment for patients with pure native aortic regurgitation (AR). However, the routine application of transfemoral TAVR for pure AR patients lacks support from randomized trials. TRIAL DESIGN: SEASON-AR trial is a prospective, multicenter, randomized, controlled, parallel-group, open-label trial, involving at least 20 sites in China, aiming to enroll 210 patients with pure native severe AR and high surgical risk. All enrolled patients are randomly assigned in a 1:1 fashion to undergo transfemoral TAVR with VitaFlowTM valve and receive guideline-directed medical therapy (GDMT) or to receive GDMT alone. The primary endpoint is the rate of major adverse cardiac events (MACE) at 12 months after the procedure, defined by the composite of all-cause mortality, disabling stroke, and rehospitalization for heart failure. The major secondary endpoints encompass various measures, including procedure-related complications, device success, 6-minute walk distance, and the occurrence of each individual component of the primary endpoint. After hospital discharge, follow-up was conducted through clinical visits or telephone contact at 1, 6, and 12 months. The follow-up will continue annually until 5 years after the index procedure to assess the long-term outcomes. CONCLUSION: SEASON-AR trial is the first study designed to investigate the clinical efficacy and safety of transfemoral TAVR with a self-expanding valve in patients with pure native severe AR with inoperable or high-risk, as compared to medical treatment only.
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Insuficiencia de la Válvula Aórtica , Prótesis Valvulares Cardíacas , Reemplazo de la Válvula Aórtica Transcatéter , Humanos , Reemplazo de la Válvula Aórtica Transcatéter/métodos , Insuficiencia de la Válvula Aórtica/cirugía , Insuficiencia de la Válvula Aórtica/epidemiología , Estudios Prospectivos , Masculino , Femenino , Anciano , Arteria Femoral , Válvula Aórtica/cirugía , Diseño de Prótesis , Accidente Cerebrovascular/prevención & control , Accidente Cerebrovascular/etiología , Accidente Cerebrovascular/epidemiología , China/epidemiología , Resultado del Tratamiento , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/prevención & controlRESUMEN
c-MYC is a hallmark of various cancers, playing a critical role in promoting tumorigenesis. The formation of G-quadruplex (G4) in the c-MYC promoter region significantly suppresses its expression. Therefore, developing small-molecule ligands to stabilize c-MYC G4 formation and subsequentially suppress c-MYC expression is an attractive topic for c-MYC-driven cancer therapy. However, achieving selective ligands for c-MYC G4 poses challenges. In this study, we developed a series of triazole-modified quinazoline (TMQ) derivatives as potential c-MYC G4 ligands and c-MYC transcription inhibitors from 4-anilinoquinazoline lead 7a using click chemistry. Importantly, the c-MYC G4 stabilizing ability and antiproliferation activity were well correlated among these new derivatives, particularly in the c-MYC highly expressed colorectal cancer cell line HCT116. Among them, compound A6 exhibited good selectivity in stabilizing c-MYC G4 and in suppressing c-MYC transcription better than 7a. This compound induced G4 formation, selectively inhibited G4-related c-MYC transcription and suppressed the progression of HCT116 cells. These findings identify a new c-MYC transcription inhibitor and provide new insights for optimizing c-MYC G4-targeting ligands.
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Compuestos de Anilina , Antineoplásicos , G-Cuádruplex , Química Clic , Proteínas Proto-Oncogénicas c-myc , Antineoplásicos/farmacología , Antineoplásicos/química , Quinazolinas/farmacología , Quinazolinas/química , Triazoles/farmacología , LigandosRESUMEN
Glycerol utilization as a carbohydrate source by Borreliella burgdorferi, the Lyme disease spirochete, is critical for its successful colonization and persistence in the tick vector. The expression of the glpFKD (glp) operon, which encodes proteins for glycerol uptake/utilization, must be tightly regulated during the enzootic cycle of B. burgdorferi. Previous studies have established that the second messenger cyclic di-GMP (c-di-GMP) is required for the activation of glp expression, while an alternative sigma factor RpoS acts as a negative regulator for glp expression. In the present study, we report identification of a cis element within the 5´ untranslated region of glp that exerts negative regulation of glp expression. Further genetic screen of known and predicted DNA-binding proteins encoded in the genome of B. burgdorferi uncovered that overexpressing Borrelia host adaptation regulator (BadR), a known global regulator, dramatically reduced glp expression. Similarly, the badR mutant significantly increased glp expression. Subsequent electrophoretic mobility shift assay analyses demonstrated that BadR directly binds to this cis element, thereby repressing glp independent of RpoS-mediated repression. The efficiency of BadR binding was further assessed in the presence of c-di-GMP and various carbohydrates. This finding highlights multi-layered positive and negative regulatory mechanisms employed by B. burgdorferi to synchronize glp expression throughout its enzootic cycle.IMPORTANCEBorreliella burgdorferi, the Lyme disease pathogen, must modulate its gene expression differentially to adapt successfully to its two disparate hosts. Previous studies have demonstrated that the glycerol uptake and utilization operon, glpFKD, plays a crucial role in spirochetal survival within ticks. However, the glpFKD expression must be repressed when B. burgdorferi transitions to the mammalian host. In this study, we identified a specific cis element responsible for the repression of glpFKD. We further pinpointed Borrelia host adaptation regulator as the direct binding protein to this cis element, thereby repressing glpFKD expression. This discovery paves the way for a deeper exploration of how zoonotic pathogens sense distinct hosts and switch their carbon source utilization during transmission.
Asunto(s)
Borrelia burgdorferi , Borrelia , Enfermedad de Lyme , Garrapatas , Animales , Borrelia/genética , Borrelia/metabolismo , Glicerol/metabolismo , Adaptación al Huésped , Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismo , Borrelia burgdorferi/genética , Borrelia burgdorferi/metabolismo , Operón , Regulación Bacteriana de la Expresión Génica , Mamíferos/genética , Mamíferos/metabolismoRESUMEN
Bladder cancer, the most common malignant tumor in the urinary system, exhibits significantly up-regulated expression of P3H4, which is associated with pathological factors. The objective of this study was to elucidate the underlying mechanism of P3H4 in bladder cancer. Initially, we analyzed P3H4 gene expression using the TCGA database and evaluated P3H4 levels in clinical samples and various bladder cell lines. P3H4 was found to be markedly overexpressed in bladder cancer samples. Subsequently, bladder cancer cells were transfected with shRNA targeting P3H4 (sh-P3H4), sh-METTL3, and P3H4 overexpression vectors (P3H4 OE). Viability, migration, and invasion of bladder cancer cells were assessed using CCK-8, wound healing, and transwell assays. Western blot analysis was performed to determine the levels of EMT-associated proteins, while RNA stability assays determined the half-life of P3H4. Knockdown of P3H4 resulted in inhibition of bladder cancer cell proliferation, migration, invasion, and EMT progression. Mechanistically, METTL3 was found to regulate the mRNA stability of P3H4 in bladder cancer. Moreover, overexpression of P3H4 reversed the inhibitory effects of METTL3 knockdown on bladder cancer cell behaviors. Stable cell lines were established by infecting EJ cells with lentiviral vectors containing sh-METTL3 or P3H4 OE. These cells were then implanted into the skin of BALB/c nude mice, and IHC analysis was used to analyze the expression levels of EMT-associated proteins. In vivo studies demonstrated that inhibition of METTL3 suppressed bladder cancer growth and EMT through P3H4. In conclusion, our findings suggest that METTL3 regulates the proliferation, metastasis, and EMT progression of bladder cancer through P3H4, highlighting its potential as a therapeutic target.