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BACKGROUND: Colchicine has been approved to reduce cardiovascular risk in patients with coronary heart disease on the basis of its potential benefits demonstrated in the COLCOT (Colchicine-Optical Coherence Tomography Trial) and LoDoCo2 studies. Nevertheless, there are limited data available about the specific impact of colchicine on coronary plaques. METHODS: This was a prospective, single-center, randomized, double-blind clinical trial. From May 3, 2021, until August 31, 2022, a total of 128 patients with acute coronary syndrome aged 18 to 80 years with lipid-rich plaque (lipid pool arc >90°) detected by optical coherence tomography were included. The subjects were randomly assigned in a 1:1 ratio to receive either colchicine (0.5 mg once daily) or placebo for 12 months. The primary end point was the change in the minimal fibrous cap thickness from baseline to the 12-month follow-up. RESULTS: Among 128 patients, 52 in the colchicine group and 52 in the placebo group completed the study. The mean age of the 128 patients was 58.0±9.8 years, and 25.0% were female. Compared with placebo, colchicine therapy significantly increased the minimal fibrous cap thickness (51.9 [95% CI, 32.8 to 71.0] µm versus 87.2 [95% CI, 69.9 to 104.5] µm; difference, 34.2 [95% CI, 9.7 to 58.6] µm; P=0.006), and reduced average lipid arc (-25.2° [95% CI, -30.6° to -19.9°] versus -35.7° [95% CI, -40.5° to -30.8°]; difference, -10.5° [95% CI, -17.7° to -3.4°]; P=0.004), mean angular extension of macrophages (-8.9° [95% CI, -13.3° to -4.6°] versus -14.0° [95% CI, -18.0° to -10.0°]; difference, -6.0° [95% CI, -11.8° to -0.2°]; P=0.044), high-sensitivity C-reactive protein level (geometric mean ratio, 0.6 [95% CI, 0.4 to 1.0] versus 0.3 [95% CI, 0.2 to 0.5]; difference, 0.5 [95% CI, 0.3 to 1.0]; P=0.046), interleukin-6 level (geometric mean ratio, 0.8 [95% CI, 0.6 to 1.1] versus 0.5 [95% CI, 0.4 to 0.7]; difference, 0.6 [95% CI, 0.4 to 0.9]; P=0.025), and myeloperoxidase level (geometric mean ratio, 1.0 [95% CI, 0.8 to 1.2] versus 0.8 [95% CI, 0.7 to 0.9]; difference, 0.8 [95% CI, 0.6 to 1.0]; P=0.047). CONCLUSIONS: Our findings suggested that colchicine resulted in favorable effects on coronary plaque stabilization at optical coherence tomography in patients with acute coronary syndrome. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04848857.
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BACKGROUND: Osteoporosis is a common metabolic disorder that significantly impacts quality of life in the elderly population. Macrophages play a crucial role in the development of osteoporosis by regulating bone metabolism through cytokine secretion. However, there is a lack of scholarly literature in the field of bibliometrics on this topic. OBJECTIVE: This study provides a detailed analysis of the research focus and knowledge structure of macrophage studies in osteoporosis using bibliometrics. METHODS: The scientific literature on macrophage research in the context of osteoporosis, retrieved from the Web of Science Core Collection (WoSCC) database spanning from January 1999 to December 2023, has been incorporated for bibliometric examination. The data is methodically analyzed and visually represented using analytical and visualization tools including VOSviewer, CiteSpace, Scimago Graphica, the Bibliometrix R package, and Pajek. RESULTS AND CONCLUSIONS: In the last quarter-century, there has been a consistent rise in the quantity of scholarly publications focusing on the relationship between macrophages and osteoporosis, resulting in a total of 1499 research documents. These studies have originated from 45 different countries, with China, South Korea, and the United States being the most prominent contributors, and the United States having the highest frequency of citations. Noteworthy research institutions involved in this field include Shanghai Jiao Tong University, Wonkwang University, Huazhong University of Science and Technology, and Seoul National University. The Journal of Bone and Mineral Research is widely regarded as the premier and most frequently referenced publication in the field. These publications involve the collaboration of 8744 authors, with Lee Myeung Su contributing the most articles, and Takayanagi being the most co-cited author. Key emerging research focal points are encapsulated in keywords such as "mTOR," "BMSCs," "bone regeneration," and "exosome." The relationships between exosome from macrophage sources and those from BMSCs, along with the regulatory role of the mTOR signaling pathway on macrophages, represent crucial directions for future development in this field. This study represents the inaugural comprehensive bibliometric analysis detailing trends and advancements in macrophage research within the osteoporosis domain. It delineates recent frontiers and hotspots, providing valuable insights for researchers in this particular area of study.
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In this work, the waste orange-peel was used as carbon source, and the orange-peel derived carbon material can be obtained through simple pyrolysis. Then, we designed the structure of orange-peel carbon aerogel grown on iron-nickel layered double hydroxides in situ to achieve the effect of carbon coating (FeNi-LDH/CA). The oxygen evolution reaction catalytic performance of FeNi-LDH/CA is excellent, far exceeding that of commercial RuO2. In 1 M KOH, the overpotential of FeNi-LDH/CA is only 250 mV (10 mA cm-2), obviously better than that of commercial RuO2 (295 mV). FeNi-LDH/CA shows good cycling stability, and after long-term i-t testing, the performance only decays by 3% after running at 100 mA cm-2 for 100 h. When used as an anode, the voltage of water-splitting is only 1.48 V at 10 mA cm-2. The rechargeable liquid zinc-air battery based on Pt/C-FeNi-LDH/CA catalyst has higher open-circuit voltage (1.543 V) and galvanostatic discharge capacity at 1.23 V (830 min, 10 mA cm-2). Moreover, the zinc-air battery based on Pt/C-FeNi-LDH/CA has a small charge-discharge voltage gap (0.65 V) at 10 mA cm-2, after 200 consecutive cycles (66 h), the charge-discharge voltage gap only increased by about 30 mV, indicating good cycling stability.
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Osteoporosis (OP) is a systemic metabolic bone disease that is characterized by decreased bone mineral density and microstructural damage to bone tissue. Recent studies have demonstrated significant advances in the research of programmed cell death (PCD) in OP. However, there is no bibliometric analysis in this research field. This study searched the Web of Science Core Collection (WoSCC) database for literature related to OP and PCD from 2000 to 2023. This study used VOSviewers 1.6.20, the "bibliometrix" R package, and CiteSpace (6.2.R3) for bibliometric and visualization analysis. A total of 2905 articles from 80 countries were included, with China and the United States leading the way. The number of publications related to PCD in OP is increasing year by year. The main research institutions are Shanghai Jiao Tong University, Chinese Medical University, Southern Medical University, Zhejiang University, and Soochow University. Bone is the most popular journal in the field of PCD in OP, and the Journal of Bone and Mineral Research is the most co-cited journal. These publications come from 14,801 authors, with Liu Zong-Ping, Yang Lei, Manolagas Stavros C, Zhang Wei, and Zhao Hong-Yan having published the most papers. Ronald S. Weinstein was co-cited most often. Oxidative stress and autophagy are the current research hot spots for PCD in OP. This bibliometric study provides the first comprehensive summary of trends and developments in PCD research in OP. This information identifies the most recent research frontiers and hot directions, which will provide a definitive reference for scholars studying PCD in OP.
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Bibliometría , Osteoporosis , Humanos , Apoptosis , Investigación Biomédica/tendenciasRESUMEN
BACKGROUND: The present study aims to determine the impact of different cuff diameters on the cuff pressure of endotracheal tubes (ETTs) when the trachea is adequately sealed. METHODS: In the present single-center clinical trial, adult patients who underwent cardiothoracic surgery were assigned to use ETTs from 2 brands (GME and GZW). The primary endpoint comprised of the following: cuff diameter, inner diameter of the ETT, manufacturer, and the number of subjects with tracheal leakage when the cuff pressure was 30 cm H2O. RESULTS: A total of 298 patients were assigned into 2 groups, based on the 2 distinct brands of ETTs: experimental group (nâ =â 122, GME brand) and control group (nâ =â 176, GZW brand). There were no significant differences in baseline characteristics. However, the cuff diameter was significantly smaller in the control group, when compared to the experimental group (Pâ =â .001), and the incidence of tracheal leakage was significantly higher in the control group (Pâ =â .001). Furthermore, the GME brand ETT had a significantly larger cuff diameter, when compared to the GZW brand ETT. CONCLUSION: The cuff size would mismatch the tracheal area in clinical practice. Therefore, chest computed tomography is recommended to routinely evaluate the tracheal cross-sectional area during anesthesia, in order to ensure the appropriate cuff size selection.
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Enfermedad Crítica , Intubación Intratraqueal , Humanos , Intubación Intratraqueal/métodos , Intubación Intratraqueal/instrumentación , Intubación Intratraqueal/efectos adversos , Masculino , Femenino , Persona de Mediana Edad , Anciano , Tráquea , Diseño de Equipo , AdultoRESUMEN
Background: Biomaterials can improve cardiac repair combined with transplantation of bone marrow mononuclear cells (BMMNCs). In this study, we compared the phenotype and cardiac repair between human heart valve-derived scaffold (hHVS) and natural protein/polycaprolactone (NP/PCL) anchored BMNNCs. Methods and results: BMMNCs were obtained from mice five days following myocardial infarction. Subsequently, BMMNCs were separately cultured on hHVS and PCL. Proliferation and cardiomyogenic differentiation were detected in vitro. Cardiac function was measured after transplantation of cell-seeded cardiac patch on MI mice. After that, the BMMNCs were collected for mRNA sequencing after culturing on the scaffolds. Upon anchoring onto hHVS or PCL, BMMNCs exhibited an increased capacity for proliferation in vitro, however, the cells on hHVS exhibited superior cardiomyogenic differentiation ability. Moreover, both BMMNCs-seeded biomaterials effectively improved cardiac function after 4 weeks of transplantation, with reduced infarction area and restricted LV remodeling. Cell-seeded hHVS was superior to cell-seeded PCL. Conclusion: BMMNCs on hHVS showed better capacity in both cell cardiac repairing and improvement for cardiac function than on PCL. Compared with seeded onto PCL, BMMNCs on hHVS had 253 genes up regulated and 189 genes down regulated. The reason for hHVS' better performance than PCL as a scaffold for BMMNCs might be due to the fact that optimized method of decellularization let more cytokines in ECM retained.
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AIM: The commonly recommended endotracheal tube cuff pressure is 20-30 cmH2O. However, some patients require a cuff pressure of >30 cmH2O to prevent air leakage. The study aims to determine the risk factors that contribute to the endotracheal tube cuff pressure of >30 cmH2O to prevent air leakage. DESIGN: A multi-centre prospective observational study. METHODS: Eligible patients undergoing mechanical ventilation in the intensive care unit of three hospitals between March 2020 and July 2022 were included. The endotracheal tube cuff pressure to prevent air leakage was determined using the minimal occlusive volume technique. The patient demographics and clinical information were collected. RESULTS: A total of 284 patients were included. Among these patients, 55 (19.37%) patients required a cuff pressure of >30 cmH2O to prevent air leakage. The multivariate logistic regression results revealed that the surgical operation (odds ratio [OR]: 8.485, 95% confidence interval [CI]: 1.066-67.525, p = 0.043) was inversely associated with the endotracheal tube cuff pressure of >30 cmH2O, while the oral intubation route (OR: 0.127, 95% CI: 0.022-0.750, p = 0.023) and cuff inner diameter minus tracheal area (OR: 0.949, 95% CI: 0.933-0.966, p < 0.001) were negatively associated with the endotracheal tube cuff pressure of >30 cmH2O. Therefore, a significant number of patients require an endotracheal tube cuff pressure of ï¼30 cmH2O to prevent air leakage. Several factors, including the surgical operation, intubation route, and difference between the cuff inner diameter and tracheal area at the T3 vertebra, should be considered when determining the appropriate cuff pressure during mechanical ventilation.
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Intubación Intratraqueal , Respiración Artificial , Humanos , Estudios Prospectivos , Masculino , Femenino , Respiración Artificial/efectos adversos , Respiración Artificial/instrumentación , Intubación Intratraqueal/efectos adversos , Intubación Intratraqueal/instrumentación , Persona de Mediana Edad , Factores de Riesgo , Anciano , Presión/efectos adversos , Unidades de Cuidados IntensivosRESUMEN
BACKGROUND: Benign prostatic hyperplasia (BPH) is the most common disease in elderly men. There is increasing evidence that periodontitis increases the risk of BPH, but the specific mechanism remains unclear. This study aimed to explore the role and mechanism of the key periodontal pathogen Porphyromonas gingivalis (P. gingivalis) in the development of BPH. METHODS: The subgingival plaque (Sp) and prostatic fluid (Pf) of patients with BPH concurrent periodontitis were extracted and cultured for 16S rDNA sequencing. Ligature-induced periodontitis, testosterone-induced BPH and the composite models in rats were established. The P. gingivalis and its toxic factor P. gingivalis lipopolysaccharide (P.g-LPS) were injected into the ventral lobe of prostate in rats to simulate its colonization of prostate. P.g-LPS was used to construct the prostate cell infection model for mechanism exploration. RESULTS: P. gingivalis, Streptococcus oralis, Capnocytophaga ochracea and other oral pathogens were simultaneously detected in the Pf and Sp of patients with BPH concurrent periodontitis, and the average relative abundance of P. gingivalis was found to be the highest. P. gingivalis was detected in both Pf and Sp in 62.5% of patients. Simultaneous periodontitis and BPH synergistically aggravated prostate histological changes. P. gingivalis and P.g-LPS infection could induce obvious hyperplasia of the prostate epithelium and stroma (epithelial thickness was 2.97- and 3.08-fold that of control group, respectively), and increase of collagen fibrosis (3.81- and 5.02-fold that of control group, respectively). P. gingivalis infection promoted prostate cell proliferation, inhibited apoptosis, and upregulated the expression of inflammatory cytokines interleukin-6 (IL-6; 4.47-fold), interleukin-6 receptor-α (IL-6Rα; 5.74-fold) and glycoprotein 130 (gp130; 4.47-fold) in prostatic tissue. P.g-LPS could significantly inhibit cell apoptosis, promote mitosis and proliferation of cells. P.g-LPS activates the Akt pathway through IL-6/IL-6Rα/gp130 complex, which destroys the imbalance between proliferation and apoptosis of prostate cells, induces BPH. CONCLUSION: P. gingivalis was abundant in the Pf of patients with BPH concurrent periodontitis. P. gingivalis infection can promote BPH, which may affect the progression of BPH via inflammation and the Akt signaling pathway.
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Interleucina-6 , Porphyromonas gingivalis , Hiperplasia Prostática , Receptores de Interleucina-6 , Masculino , Hiperplasia Prostática/complicaciones , Porphyromonas gingivalis/patogenicidad , Ratas , Humanos , Animales , Interleucina-6/análisis , Interleucina-6/metabolismo , Próstata , Periodontitis/complicaciones , Periodontitis/microbiología , Anciano , Persona de Mediana Edad , Ratas Sprague-Dawley , Modelos Animales de Enfermedad , Transducción de Señal/fisiologíaRESUMEN
In this work, PbPd0.9V0.1O2 and PbPd0.9Gd0.1O2 thin films with (002) preferred orientation were prepared using a pulsed laser deposition technique. The temperature dependence of resistivities ρI(T) was investigated under various applied DC currents. Colossal electroresistance (CER) effects were found in PbPd0.9V0.1O2 and PbPd0.9Gd0.1O2. It was found that the positive CER values of PbPd0.9V0.1O2 and PbPd0.9Gd0.1O2 reach 3816% and 154% for I = 1.00 µA at 10 K, respectively. In addition, the ρI(T) cycle curves of PbPd0.9V0.1O2 and PbPd0.9Gd0.1O2 thin films showed a critical temperature similar to that of PbPdO2 (Tc = 260 K). Particularly, charge transfer between O1- and O2- was confirmed by in situ XPS. Additionally, based on first-principles calculations and internal electric field models, the CER and magnetic sources in PbPd0.9V0.1O2 and PbPd0.9Gd0.1O2 can be well explained. Finally, it was found that thin film samples doped with V and G ions exhibit weak localization (WL) and weak anti-localization (WAL) quantum transport properties. Ion doping leads to a transition from WAL to WL. The study results indicate that PbPdO2, one of the few oxide topological insulators, can exhibit novel quantum transport behavior after ion doping.
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INTRODUCTION: The natural outcome of coronary plaque in acute coronary syndrome (ACS) patients with chronic kidney disease (CKD) is unique, which can be analyzed quantitatively by optical flow ratio (OFR) software. METHODS: A total of 184 ACS patients with at least one nonculprit subclinical atherosclerosis (NSA) detected by optical coherence tomography (OCT) at baseline and 1-year follow-up were divided into non-CKD group (n = 106, estimated glomerular filtration rate (eGFR)> 90 mL/(min×1.73 m2)) and mild CKD group (n = 78, 60≤eGFR<90 mL/(min×1.73 m2)). Changes of normalized total atheroma volume (TAVn) of NSA was the primary endpoint at the 1-year follow-up. RESULTS: Patients with mild CKD showed more TAVn progression of NSA than non-CKD (p = 0.019) from baseline to the 1-year follow-up, which was mainly due to an increase in calcium TAVn (p<0.001). The morphological change in the maximal calcification thickness (p = 0.026) was higher and the change in the distance from the calcified surface to the contralateral coronary media membrane (ΔC-to-M) at the maximal cross-sectional calcium area was lower (p<0.001) in mild CKD group than in non-CKD group. Mild CKD had more NSA related MACEs at the 5-year follow-up than non-CKD (30.8% vs. 5.8%, p = 0.045). CONCLUSIONS: Mild CKD patients had more plaque progression of NSA which showed the increase of calcium component with more protrusion into the lumen morphologically at the 1-year follow-up and a higher corresponding incidence of NSA-related MACEs at the 5-year follow-up. TRIAL REGISTRATION: Clinical Trial registration ClinicalTrials.gov. NCT02140801. https://classic.clinicaltrials.gov/ct2/show/NCT02140801.
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Síndrome Coronario Agudo , Tasa de Filtración Glomerular , Insuficiencia Renal Crónica , Tomografía de Coherencia Óptica , Humanos , Masculino , Femenino , Síndrome Coronario Agudo/patología , Síndrome Coronario Agudo/diagnóstico por imagen , Insuficiencia Renal Crónica/patología , Insuficiencia Renal Crónica/complicaciones , Persona de Mediana Edad , Estudios de Seguimiento , Anciano , Placa Aterosclerótica/diagnóstico por imagen , Placa Aterosclerótica/patología , Progresión de la Enfermedad , Aterosclerosis/patología , Aterosclerosis/diagnóstico por imagen , Aterosclerosis/complicaciones , Enfermedad de la Arteria Coronaria/patología , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Enfermedad de la Arteria Coronaria/complicaciones , Relevancia ClínicaRESUMEN
CRISPR/Cas technology has made great progress in the field of live-cell imaging beyond genome editing. However, effective and easy-to-use CRISPR systems for labeling multiple RNAs of interest are still needed. Here, we engineered a CRISPR/dCas12a system that enables the specific recognition of the target RNA under the guidance of a PAM-presenting oligonucleotide (PAMmer) to mimic the PAM recognition mechanism for DNA substrates. We demonstrated the feasibility and specificity of this system for specifically visualizing endogenous mRNA. By leveraging dCas12a-mediated precursor CRISPR RNA (pre-crRNA) processing and the orthogonality of dCas12a from different bacteria, we further demonstrated the proposed system as a simple and versatile molecular toolkit for multiplexed imaging of different types of RNA transcripts in live cells with high specificity. This programmable dCas12a system not only broadens the RNA imaging toolbox but also facilitates diverse applications for RNA manipulation.
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Sistemas CRISPR-Cas , ARN , ARN/genética , Sistemas CRISPR-Cas/genética , ARN Guía de Sistemas CRISPR-Cas , Edición Génica/métodos , Bacterias/genética , Precursores del ARNRESUMEN
BACKGROUND: Gallstones are common lesions that often require surgical intervention. Laparoscopic cholecystectomy is the treatment of choice for symptomatic gallstones. Preoperatively, the anatomical morphology of the cystic duct (CD), needs to be accurately recognized, especially when anatomical variations occur in the CD, which is otherwise prone to bile duct injury. However, at present, there is no optimal classification system for CD morphology applicable in clinical practice, and the relationship between anatomical variations in CDs and gallstones remains to be explored. AIM: To create a more comprehensive clinically applicable classification of the morphology of CD and to explore the correlations between anatomic variants of CD and gallstones. METHODS: A total of 300 patients were retrospectively enrolled from October 2021 to January 2022. The patients were divided into two groups: The gallstone group and the nongallstone group. Relevant clinical data and anatomical data of the CD based on magnetic resonance cholangiopancreatography (MRCP) were collected and analyzed to propose a morphological classification system of the CD and to explore its relationship with gallstones. Multivariate analysis was performed using logistic regression analyses to identify the independent risk factors using variables that were significant in the univariate analysis. RESULTS: Of the 300 patients enrolled in this study, 200 (66.7%) had gallstones. The mean age was 48.10 ± 13.30 years, 142 (47.3%) were male, and 158 (52.7%) were female. A total of 55.7% of the patients had a body mass index (BMI) ≥ 24 kg/m2. Based on the MRCP, the CD anatomical typology is divided into four types: Type I: Linear, type II: n-shaped, type III: S-shaped, and type IV: W-shaped. Univariate analysis revealed differences between the gallstone and nongallstone groups in relation to sex, BMI, cholesterol, triglycerides, morphology of CD, site of CD insertion into the extrahepatic bile duct, length of CD, and angle between the common hepatic duct and CD. According to the multivariate analysis, female, BMI (≥ 24 kg/m2), and CD morphology [n-shaped: Odds ratio (OR) = 10.97, 95% confidence interval (95%CI): 5.22-23.07, P < 0.001; S-shaped: OR = 4.43, 95%CI: 1.64-11.95, P = 0.003; W-shaped: OR = 7.74, 95%CI: 1.88-31.78, P = 0.005] were significantly associated with gallstones. CONCLUSION: The present study details the morphological variation in the CD and confirms that CD tortuosity is an independent risk factor for gallstones.
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BACKGROUND: Bladder, kidney and prostate cancers make significant contributors to cancer burdens. Exploring their cross-country inequalities may inform equitable strategies to meet the 17 sustainable development goals before 2030. METHODS: We analyzed age-standardized disability-adjusted life-years (ASDALY) rates for the three cancers based on Global Burden of Diseases Study 2019. We quantified the inequalities using slope index of inequality (SII, absolute measure) and concentration index (relative measure) associated with national sociodemographic index. RESULTS: Varied ASDALY rates were observed in the three cancers across 204 regions. The SII decreased from 35.15 (95% confidence interval, CI: 29.34 to 39.17) in 1990 to 15.81 (95% CI: 7.99 to 21.79) in 2019 for bladder cancers, from 78.94 (95% CI: 75.97 to 81.31) in 1990 to 59.79 (95% CI: 55.32 to 63.83) in 2019 for kidney cancer, and from 192.27 (95% CI: 137.00 to 241.05) in 1990 to - 103.99 (95% CI: - 183.82 to 51.75) in 2019 for prostate cancer. Moreover, the concentration index changed from 12.44 (95% CI, 11.86 to 12.74) in 1990 to 15.72 (95% CI, 15.14 to 16.01) in 2019 for bladder cancer, from 33.88 (95% CI: 33.35 to 34.17) in 1990 to 31.13 (95% CI: 30.36 to 31.43) in 2019 for kidney cancer, and from 14.61 (95% CI: 13.89 to 14.84) in 1990 to 5.89 (95% CI: 5.16 to 6.26) in 2019 for prostate cancer. Notably, the males presented higher inequality than females in both bladder and kidney cancer from 1990 to 2019. CONCLUSIONS: Different patterns of inequality were observed in the three cancers, necessitating tailored national cancer control strategies to mitigate disparities. Priority interventions for bladder and kidney cancer should target higher socioeconomic regions, whereas interventions for prostate cancer should prioritize the lowest socioeconomic regions. Additionally, addressing higher inequality in males requires more intensive interventions among males from higher socioeconomic regions.
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Neoplasias Renales , Neoplasias de la Próstata , Masculino , Humanos , Factores Socioeconómicos , Carga Global de Enfermedades , Vejiga Urinaria , Costo de Enfermedad , Neoplasias Renales/epidemiología , Riñón , Neoplasias de la Próstata/epidemiologíaRESUMEN
BACKGROUND AND OBJECTIVES: To evaluate the potential benefits of Bacteroides fragilis 839 (BF839), a next-generation probiotics, in reducing myelosuppression and gastrointestinal toxicity associated with chemotherapy in breast cancer patient. METHODS AND STUDY DESIGN: 40 women with early breast cancer were randomly assigned to the BF839 (n=20) or placebo (n=20) during the administration of adjuvant chemotherapy (4 cycles of epirubicin 100mg/m2 and cyclophosphamide 600mg/m2). Myelosuppression and gastrointestinal adverse effects were monitored in both groups. RESULTS: Throughout the four treatment cycles, the percentage of patients experiencing myelosuppression was 42.5% in the BF839 group, significantly lower than the 66.3% observed in the control group (p=0.003). Two patients in the BF839 group and three patients in the placebo group received recombinant human granulocyte colony-stimulating factor (rhG-CSF) due to leuko-penia/neutropenia. When considering an ITT analysis, which included all patients regardless of rhG-CSF treatment, the BF839 group exhibited less reduction from baseline in white blood cells (-0.31±1.19 vs -1.15±0.77, p=0.012) and neutrophils (0.06±1.00 vs -0.84±0.85, p=0.004) compared to the placebo group. The difference became even more significant when excluding the patients who received rhG-CSF injections. Throughout the four treatment cycles, compared to the placebo group, the BF839 group had significantly lower rates of 3-4 grade nausea (35.0% vs 71.3%, p=0.001), vomiting (20.0% vs 45.0%, p=0.001), and diarrhea (15.0% vs 30.0%, p=0.023). CONCLUSIONS: These findings suggest that BF839 has the potential to effectively mitigate myelosuppression and gastrointestinal toxicity associated with chemotherapy in breast cancer patients.
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Antineoplásicos , Neoplasias de la Mama , Femenino , Humanos , Antineoplásicos/efectos adversos , Bacteroides fragilis , Neoplasias de la Mama/tratamiento farmacológico , Ciclofosfamida/efectos adversos , Epirrubicina/efectos adversos , Factor Estimulante de Colonias de Granulocitos/uso terapéutico , Proteínas Recombinantes/uso terapéuticoRESUMEN
PbPdO2, a gapless semiconductor, can be transformed into a spin gapless semiconductor structure by magnetic ion doping. This unique band-gap structure serves as the foundation for its distinctive physical properties. In this study, PbPd1-xMnxO2 (x = 0.05, 0.1, 0.15) thin films with (002) preferred orientation were prepared by laser pulse deposition (PLD). The structural, electroresistive and magnetoresistive properties were systematically characterized, and the results suggest that films with different Mn doping ratios exhibit a current-induced positive colossal electroresistance (CER), and the CER values of PbPd1-xMnxO2 thin films increase with the increase of Mn doping concentration. The CER values are several fold magnitudes higher compared to those of the previously reported PbPdO2 films possessing identical (002) orientation. Combined with first-principles calculation, the underlying influence mechanism of Mn doping on CER is elucidated. In situ X-ray photoelectron spectroscopy (XPS) demonstrates a close correlation between the positive CER and the band gap change induced by oxygen vacancies in PbPd1-xMnxO2. Additionally, it is observed that Mn-doped films exhibit weak localization (WL) and weak anti-localization (WAL) quantum transport. Moreover, it is found that Mn doping can lead to a transition from WAL to WL; a small amount of Mn doping significantly enhances the weak anti-localization effect. However, with increasing Mn concentration, the WAL effect is conversely weakened. The results of studies suggest strongly that PbPdO2, one of the few oxide topological insulators, can display novel quantum transport behavior by ion doping.
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The human cerebral cortex is organized into functionally segregated but synchronized regions bridged by the structural connectivity of white matter pathways. While structure-function coupling has been implicated in cognitive development and neuropsychiatric disorders, studies yield inconsistent findings. The extent to which the structure-function coupling reflects reliable individual differences or primarily group-common characteristics remains unclear, at both the global and regional brain levels. By leveraging two independent, high-quality datasets, we found that the graph neural network accurately predicted unseen individuals' functional connectivity from structural connectivity, reflecting a strong structure-function coupling. This coupling was primarily driven by network topology and was substantially stronger than that of the linear models. Moreover, we observed that structure-function coupling was dominated by group-common effects, with subtle yet significant individual-specific effects. The regional group and individual effects of coupling were hierarchically organized across the cortex along a sensorimotor-association axis, with lower group and higher individual effects in association cortices. These findings emphasize the importance of considering both group and individual effects in understanding cortical structure-function coupling, suggesting insights into interpreting individual differences of the coupling and informing connectivity-guided therapeutics.
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Na-ion batteries (NIBs) have attracted great interest as a possible technology for grid-scale energy storage for the past few years owing to the wide distribution, low cost and environmental friendliness of sodium resources and similar chemical mechanisms to those of established Li-ion batteries (LIBs). Nonetheless, the implementation of NIBs is seriously hindered because of their low rate capability and cycling stability. This is mainly because the large ionic size of Na+ can reduce the structural stability and cause sluggish reaction kinetics of electrode materials. Herein, three-dimensional nanoarchitectured coral-like CoSe2@N-doped carbon (CL-CoSe2@NC) was synthesized through solvothermal and selenizing techniques. As a result, CL-CoSe2@NC for NIBs at 2 A g-1 exhibits an ultrahigh specific capacity of 345.4 mA h g-1 after 2800 cycles and a superhigh initial coulombic efficiency (ICE) of 93.1%. Ex situ XRD, HRTEM, SAED and XPS were executed to study the crystal structure evolution between Na and CoSe2 during sodiation/de-sodiation processes. The aforementioned results indicate that the improved sodium storage property of CL-CoSe2@NC could be attributed to better electrode kinetics and a stable SEI film because of the 3D nanoarchitecture and the existence of the NC layer.
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The formation of membrane-less organelles is driven by multivalent weak interactions while mediation of such interactions by small molecules remains an unparalleled challenge. Here, we uncovered a bivalent inhibitor that blocked the recruitment of TDRD3 by the two methylated arginines of G3BP1. Relative to the monovalent inhibitor, this bivalent inhibitor demonstrated an enhanced binding affinity to TDRD3 and capability to suppress the phase separation of methylated G3BP1, TDRD3, and RNAs, and in turn inhibit the stress granule growth in cells. Our result paves a new path to mediate multivalent interactions involved in SG assembly for potential combinational chemotherapy by bivalent inhibitors.
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ADN Helicasas , ARN Helicasas , ADN Helicasas/metabolismo , ARN Helicasas/metabolismo , Proteínas de Unión a Poli-ADP-Ribosa/metabolismo , Proteínas con Motivos de Reconocimiento de ARN/metabolismo , Separación de Fases , Gránulos Citoplasmáticos/metabolismoRESUMEN
Introduction: Thyroid metastasis from clear cell renal cell carcinoma (ccRCC) is relatively rare, so ultrasound doctors lack experience with the disease, which can easily lead to misdiagnosis. We describe three cases of thyroid metastasis from ccRCC detected 12, 8, and 7 years after nephrectomy. Case presentation: The first patient, a 78-year-old woman, was admitted to our institution for hoarseness and progressive dyspnea. Ultrasonography revealed bilateral thyroid nodules and abnormal cervical lymph nodes. Fine-needle aspiration biopsy (FNAB) and core needle biopsy (CNB) of the thyroid was nondiagnostic. The other two patients, a 54-year-old man and a 65-year-old man, were admitted to our institution for a goiter pressing on the trachea. In each case, ultrasonography revealed a partially cystic nodule of the left lobe of the thyroid gland. Histological examination of three patients after thyroidectomy showed thyroid metastasis from ccRCC. Discussion/Conclusion: For patients with a history of ccRCC, long-term follow-up and routine thyroid ultrasonography should be performed. If a new thyroid nodule is found during the examination, metastases should be highly suspected. FNAB should be performed, even if benign ultrasound features seem to be in evidence. If the diagnosis of FNAB is incorrect and inconclusive, CNB should be performed.
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Carcinoma de Células Renales , Carcinoma , Neoplasias Renales , Neoplasias de la Tiroides , Nódulo Tiroideo , Masculino , Femenino , Humanos , Anciano , Persona de Mediana Edad , Carcinoma de Células Renales/diagnóstico por imagen , Neoplasias de la Tiroides/diagnóstico por imagen , Nódulo Tiroideo/diagnóstico por imagen , Carcinoma/diagnóstico , Ultrasonografía , Neoplasias Renales/diagnóstico por imagenRESUMEN
Carbon materials have a very wide range of applications in the field of electrocatalysis, both as catalyst bodies and as excellent supports for catalysts. In this work, we obtained a graphitic-like orange-peel derived carbon (OPC) material through pre-carbonization and KOH activation strategies using discarded orange-peel as a raw material. OPC has good graphitization characteristics and a few-layer structure, making it very suitable as a support for nanoparticle catalysts. In order to compare the performance of OPC, we used commercial graphene as the benchmark, made two carbon materials uniformly loaded with ruthenium nanoparticles under the same conditions, and obtained two HER catalysts (Ru/OPC and Ru/rGO). The results indicate that Ru/OPC has excellent HER catalytic performance under alkaline conditions, not only superior to Ru/rGO, but also surpassing commercial Pt/C. In 1 M KOH; the overpotential of Ru/OPC is only 3 mV at -10 mA cm-2, greatly exceeding those of Ru/rGO (100 mV) and Pt/C (31 mV). Under high current density (j), the performance of Ru/OPC is even better; the overpotential is 79 mV and 136 mV at -100 mA cm-2 and -200 mA cm-2, respectively. More importantly, Ru/OPC also has a very high TOF and long-term stability, with a TOF of up to 10.62 H2 s-1 at an overpotential of 100 mV and almost no attenuation after 72 h of operation at -50 mA cm-2. Ru/OPC also exhibits good catalytic performance under acidic conditions, significantly superior to that of Ru/rGO. For Ru/OPC, the overpotential is 86 mV, 167 mV and 214 mV at -10 mA cm-2, -100 mA cm-2 and -200 mA cm-2, respectively. Under the same conditions, the overpotential of Ru/rGO is 143 mV, 253 mV and 306 mV at -10 mA cm-2, -100 mA cm-2 and -200 mA cm-2, respectively.