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Cluster analysis, a pivotal step in single-cell sequencing data analysis, presents substantial opportunities to effectively unveil the molecular mechanisms underlying cellular heterogeneity and intercellular phenotypic variations. However, the inherent imperfections arise as different clustering algorithms yield diverse estimates of cluster numbers and cluster assignments. This study introduces Single Cell Consistent Clustering based on Spectral Matrix Decomposition (SCSMD), a comprehensive clustering approach that integrates the strengths of multiple methods to determine the optimal clustering scheme. Testing the performance of SCSMD across different distances and employing the bespoke evaluation metric, the methodological selection undergoes validation to ensure the optimal efficacy of the SCSMD. A consistent clustering test is conducted on 15 authentic scRNA-seq datasets. The application of SCSMD to human embryonic stem cell scRNA-seq data successfully identifies known cell types and delineates their developmental trajectories. Similarly, when applied to glioblastoma cells, SCSMD accurately detects pre-existing cell types and provides finer sub-division within one of the original clusters. The results affirm the robust performance of our SCSMD method in terms of both the number of clusters and cluster assignments. Moreover, we have broadened the application scope of SCSMD to encompass larger datasets, thereby furnishing additional evidence of its superiority. The findings suggest that SCSMD is poised for application to additional scRNA-seq datasets and for further downstream analyses.
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Algoritmos , Análisis de la Célula Individual , Humanos , Análisis de la Célula Individual/métodos , Análisis por Conglomerados , Biología Computacional/métodos , Glioblastoma/genética , Glioblastoma/patología , Glioblastoma/metabolismoRESUMEN
In patients with nasopharyngeal carcinoma (NPC), the alteration of immune responses in peripheral blood remains unclear. In this study, we established an immune cell profile for patients with NPC and used flow cytometry and machine learning (ML) to identify the characteristics of this profile. After isolation of circulating leukocytes, the proportions of 104 immune cell subsets were compared between NPC group and the healthy control group (HC). Data obtained from the immune cell profile were subjected to ML training to differentiate between the immune cell profiles of the NPC and HC groups. We observed that subjects in the NPC group presented higher proportions of T cells, memory B cells, short-lived plasma cells, IgG-positive B cells, regulatory T cells, MHC II+ T cells, CTLA4+ T cells and PD-1+ T cells than subjects in the HC group, indicating weaker and compromised cellular and humoral immune responses. ML revealed that monocytes, PD-1+ CD4 T cells, memory B cells, CTLA4+ CD4 Treg cells and PD-1+ CD8 T cells were strongly contributed to the difference in immune cell profiles between the NPC and HC groups. This alteration can be fundamental in developing novel immunotherapies for NPC.
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Citometría de Flujo , Aprendizaje Automático , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas , Humanos , Carcinoma Nasofaríngeo/inmunología , Carcinoma Nasofaríngeo/patología , Citometría de Flujo/métodos , Masculino , Femenino , Persona de Mediana Edad , Neoplasias Nasofaríngeas/inmunología , Neoplasias Nasofaríngeas/patología , Adulto , Receptor de Muerte Celular Programada 1/metabolismo , Linfocitos T CD8-positivos/inmunología , Estudios de Casos y Controles , AncianoRESUMEN
Metabolic reprogramming is recognized as a hallmark of cancer, enabling cancer cells to acquire essential biomolecules for cell growth, often characterized by upregulated glycolysis and/or fatty acid synthesis-related genes. The transcription factor forkhead box M1 (FOXM1) has been implicated in various cancers, contributing significantly to their development, including colorectal cancer (CRC), a major global health concern. Despite FOXM1's established role in cancer, its specific involvement in the Warburg effect and fatty acid biosynthesis in CRC remains unclear. We analyzed The Cancer Genome Atlas (TCGA) Colonic Adenocarcinoma and Rectal Adenocarcinoma (COADREAD) datasets to derive the correlation of the expression levels between FOXM1 and multiple genes and the survival prognosis based on FOXM1 expression. Using two human CRC cell lines, HT29 and HCT116, we conducted RNAi or plasmid transfection procedures, followed by a series of assays, including RNA extraction, quantitative real-time polymerase chain reaction, Western blot analysis, cell metabolic assay, glucose uptake assay, Oil Red O staining, cell viability assay, and immunofluorescence analysis. Higher expression levels of FOXM1 correlated with a poorer survival prognosis, and the expression of FOXM1 was positively correlated with glycolysis-related genes SLC2A1 and LDHA, de novo lipogenesis-related genes ACACA and FASN, and MYC. FOXM1 appeared to modulate AKT/mammalian target of rapamycin (mTOR) signaling, the expression of c-Myc, proteins related to glycolysis and fatty acid biosynthesis, and glucose uptake, as well as extracellular acidification rate in HT29 and HCT116 cells. In summary, FOXM1 plays a regulatory role in glycolysis, fatty acid biosynthesis, and cellular energy consumption, thereby influencing CRC cell growth and patient prognosis.NEW & NOTEWORTHY Transcription factor forkhead box M1 (FOXM1) regulates glycolysis, fatty acid biosynthesis, and cellular energy consumption, which, together, controls cell growth and patient prognosis in colorectal cancer (CRC).
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Neoplasias Colorrectales , Proteína Forkhead Box M1 , Humanos , Proteína Forkhead Box M1/metabolismo , Proteína Forkhead Box M1/genética , Neoplasias Colorrectales/metabolismo , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/patología , Células HT29 , Células HCT116 , Glucólisis , Regulación Neoplásica de la Expresión Génica , Efecto Warburg en Oncología , Transducción de Señal , Proliferación Celular , Reprogramación Celular/fisiología , Serina-Treonina Quinasas TOR/metabolismo , Serina-Treonina Quinasas TOR/genética , Proteínas Proto-Oncogénicas c-akt/metabolismo , Reprogramación MetabólicaRESUMEN
OBJECTIVE: To evaluate the feasibility of developing a computer vision algorithm that uses preoperative computed tomography (CT) scans to predict superior mesenteric artery (SMA) margin status in patients undergoing Whipple for pancreatic ductal adenocarcinoma (PDAC), and to compare algorithm performance to that of expert abdominal radiologists and surgical oncologists. SUMMARY BACKGROUND DATA: Complete surgical resection is the only chance to achieve a cure for PDAC; however, current modalities to predict vascular invasion have limited accuracy. METHODS: Adult patients with PDAC who underwent Whipple and had preoperative contrast-enhanced CT scans were included (2010-2022). The SMA was manually annotated on the CT scans, and we trained a U-Net algorithm for SMA segmentation and a ResNet50 algorithm for predicting SMA margin status. Radiologists and surgeons reviewed the scans in a blinded fashion. SMA margin status per pathology reports was the reference. RESULTS: Two hundred patients were included. Forty patients (20%) had a positive SMA margin. For the segmentation task, the U-Net model achieved a Dice Similarity Coefficient of 0.90. For the classification task, all readers demonstrated limited sensitivity, although the algorithm had the highest sensitivity at 0.43 (versus 0.23 and 0.36 for the radiologists and surgeons, respectively). Specificity was universally excellent, with the radiologist and algorithm demonstrating the highest specificity at 0.94. Finally, the accuracy of the algorithm was 0.85 versus 0.80 and 0.76 for the radiologists and surgeons, respectively. CONCLUSIONS: We demonstrated the feasibility of developing a computer vision algorithm to predict SMA margin status using preoperative CT scans, highlighting its potential to augment the prediction of vascular involvement.
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BACKGROUND: Acute lung injury (ALI) is a life-threatening respiratory condition characterized by severe inflammation and lung tissue damage, frequently causing rapid respiratory failure and long-term complications. The microRNA let-7a-5p is involved in the progression of lung injury, inflammation, and fibrosis by regulating immune cell activation and cytokine production. This study aims to use an innovative cellular electroporation platform to generate extracellular vesicles (EVs) carring let-7a-5p (EV-let-7a-5p) derived from transfected Wharton's jelly-mesenchymal stem cells (WJ-MSCs) as a potential gene therapy for ALI. METHODS: A cellular nanoporation (CNP) method was used to induce the production and release of EV-let-7a-5p from WJ-MSCs transfected with the relevant plasmid DNA. EV-let-7a-5p in the conditioned medium were isolated using a tangential flow filtration (TFF) system. EV characterization followed the minimal consensus guidelines outlined by the International Society for Extracellular Vesicles. We conducted a thorough set of therapeutic assessments, including the antifibrotic effects using a transforming growth factor beta (TGF-ß)-induced cell model, the modulation effects on macrophage polarization, and the influence of EV-let-7a-5p in a rat model of hyperoxia-induced ALI. RESULTS: The CNP platform significantly increased EV secretion from transfected WJ-MSCs, and the encapsulated let-7a-5p in engineered EVs was markedly higher than that in untreated WJ-MSCs. These EV-let-7a-5p did not influence cell proliferation and effectively mitigated the TGF-ß-induced fibrotic phenotype by downregulating SMAD2/3 phosphorylation in LL29 cells. Furthermore, EV-let-7a-5p regulated M2-like macrophage activation in an inflammatory microenvironment and significantly induced interleukin (IL)-10 secretion, demonstrating their modulatory effect on inflammation. Administering EVs from untreated WJ-MSCs slightly improved lung function and increased let-7a-5p expression in plasma in the hyperoxia-induced ALI rat model. In comparison, EV-let-7a-5p significantly reduced macrophage infiltration and collagen deposition while increasing IL-10 expression, causing a substantial improvement in lung function. CONCLUSION: This study reveals that the use of the CNP platform to stimulate and transfect WJ-MSCs could generate an abundance of let-7a-5p-enriched EVs, which underscores the therapeutic potential in countering inflammatory responses, fibrotic activation, and hyperoxia-induced lung injury. These results provide potential avenues for developing innovative therapeutic approaches for more effective interventions in ALI.
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Lesión Pulmonar Aguda , Vesículas Extracelulares , Hiperoxia , MicroARNs , Ratas , Animales , Células Cultivadas , Hiperoxia/metabolismo , Inflamación , MicroARNs/genética , MicroARNs/metabolismo , Factor de Crecimiento Transformador beta/genética , Factor de Crecimiento Transformador beta/metabolismo , Vesículas Extracelulares/fisiología , Fibrosis , Lesión Pulmonar Aguda/terapia , Lesión Pulmonar Aguda/metabolismoRESUMEN
Postpartum hemorrhage (PPH) remains the leading cause of maternal mortality, primarily attributed to uterine atony. Both the World Health Organization (WHO) and the International Federation of Gynecology and Obstetrics (FIGO) endorse the use of misoprostol not only for the prevention but also for the treatment of PPH. However, the administration of misoprostol is commonly associated with transient pyrexia, attributed to a shift in the hypothalamic set point observed in certain animal studies. Misoprostol-induced hyperpyrexia can occasionally manifest with a prodrome of shivering, particularly when administered via the sublingual route, which achieves a higher and faster maximum plasma concentration compared to vaginal and rectal routes. General management strategies to reduce fever involve removing clothing and blankets, applying cool compresses, administering oral acetaminophen, and ensuring adequate hydration. While some cases have reported misoprostol-induced convulsions, hyperpyrexia leading to convulsions and subsequent rhabdomyolysis is a rare and potentially lethal side effect. In this case presentation, we emphasize a scenario where misoprostol was employed for the treatment of PPH but led to rhabdomyolysis. Our goal is to highlight the side effects of misoprostol and the significance of considering the initial combination of misoprostol with anti-pyretic management to minimize the risk of hyperthermia-related side effects and prevent additional severe complications.
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Leakage is a high-incidence disease of embankment dams, and efficiently addressing this disease guarantees the safe operation of dams. Underwater leakage self-priming plugging technology is a new technology that utilizes the melting and solidifying characteristics of phase-change materials and the negative pressure in the leakage entry area to accurately plug the leakage. However, little is yet known about the underwater melting process of phase-change materials and how their characteristics influence the plugging effect. In this study, three kinds of phase-change materials, namely, paraffin, rosin, and stearic acid, were used to conduct underwater leakage self-priming plugging tests, observe and analyze the underwater melting process, and compare the plugging effects. The results showed that the underwater melting process of phase-change materials exhibited different plugging window periods depending on their melting points, specific heat capacities, and mobilities, which were the main factors affecting their plugging effects. In the final plugging stage, paraffin had the best plugging effect, but the material strength was low; rosin had good plugging compactness, but the fluidity performance was poor, and the material effective utilization was low; stearic acid had a low melting point but dispersed easily. Therefore, a blocking material with a suitable blocking window period can be produced by adjusting the material properties accordingly for an improved blocking effect.
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BACKGROUND A traumatic coronary artery dissection is a rare but severe complication of chest trauma that can result in blockage of the coronary artery. The clinical symptoms can vary considerably, from asymptomatic arrhythmia to acute myocardial infarction and sudden death. This report describes a young man with coronary artery dissection following blunt chest trauma from a motorcycle accident presenting with ventricular fibrillation due to acute myocardial infarction, which was treated with percutaneous transluminal coronary angioplasty and extracorporeal membrane oxygenation. CASE REPORT We present a 21-year-old man with chest contusion from a motorcycle accident who experienced sudden collapse due to ventricular fibrillation and acute myocardial infarction. The patient was resuscitated with extracorporeal membrane oxygenation, and 12-lead electrocardiogram showed sinus tachycardia with a hyperacute T-wave and ST elevation in leads V2-V6. Percutaneous coronary intervention revealed dissection from the ostial to proximal portion of the left anterior descending artery, and traumatic coronary artery dissection was confirmed. He was successfully treated with percutaneous transluminal coronary angioplasty, in which a drug-eluting stent was inserted to enhance blood flow in the left anterior descending artery, resulting in TIMI 2 flow restoration. After 16 days of intensive care, he was discharged and was well at a 3-month follow-up. CONCLUSIONS This report describes a case with the rare association between blunt chest trauma and coronary artery dissection and highlights that coronary artery dissection can result in ST-elevation myocardial infarction. Extracorporeal membrane oxygenation can protect the patient's circulation for coronary angioplasty. Therefore, early detection and intensive resuscitation can prevent disastrous outcomes.
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Accidentes de Tránsito , Motocicletas , Infarto del Miocardio , Heridas no Penetrantes , Humanos , Masculino , Infarto del Miocardio/terapia , Adulto Joven , Heridas no Penetrantes/complicaciones , Heridas no Penetrantes/terapia , Oxigenación por Membrana Extracorpórea , Vasos Coronarios/lesiones , Intervención Coronaria Percutánea , Electrocardiografía , Traumatismos Torácicos/complicaciones , Disección Aórtica/complicaciones , Disección Aórtica/terapia , Stents Liberadores de Fármacos , Aneurisma Coronario/terapia , Aneurisma Coronario/etiología , Angioplastia Coronaria con BalónRESUMEN
Controlled-release tablets offer several benefits, such as controlled release, odor masking, ease of use, stability, extended shelf life, and reduced production costs. This study developed combined curcumin controlled-release tablets (CCCTs) to increase the bioavailability of curcumin with hydroxypropyl methylcellulose (HPMC), chitosan, and sodium alginate. The hardness of the CCCTs was 5.63-1.98 kgf, friability was 0.00-1.22%, and disintegration time was 0.00-401.25 min. Differential scanning calorimetry and Fourier-transform infrared spectroscopy indicated a high compatibility between the excipients and curcumin. CCCTs with chitosan formed a gel structure, impeded disintegration, and reduced the release rate to 72.5% in simulated gastric fluid. In simulated intestinal fluid, CCCT with the HPMC-sodium alginate group formed a polyelectrolyte membrane hydrogel to prolong release from 6 to 12 h. This study developed various CCCT formulations that can be delivered through the gastric or intestinal tracts, using chitosan and HPMC-sodium alginate as excipients, respectively. CCCT can be used as a reference strategy for controlled-release curcumin delivery in the functional and healthcare supplement development.
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Patients with peripheral artery disease (PAD) are at high risk of major adverse limb events (MALEs) and major adverse cardiovascular events (MACEs). CHA2DS2-VASc is a prognostic score for atrial fibrillation stroke risk; however, no study has evaluated its predictive ability for MALEs and MACEs in PAD patients who underwent percutaneous transluminal angioplasty. We conducted a retrospective cohort study on patients from Taiwan with PAD. The patients were stratified into four risk groups based on their modified CHA2DS2-VASc score. Cox proportional hazard models, 10-fold cross-validation, and receiver operating characteristic (ROC) analyses were utilized to evaluate the predictive ability of CHA2DS2-VASc for MALEs, MACEs, and MALEs + MACEs. Kaplan-Meier analysis estimated the survival probability of the risk groups. CHA2DS2-VASc was found to be a significant predictor of MACEs (hazard ratio (HR) 3.52 (95% confidence interval (95% CI) 1.00-12.12; p = 0.048), HR 4.18 (95% CI 1.19-14.36; p = 0.023), and HR 5.08 (95% CI 1.49-17.36; p = 0.009), for moderate-, high-, and very high-risk groups, respectively), while for MALEs and MALEs + MACEs, significance was achieved only for the high-risk group using a univariate model. For the multivariate adjusted model, the score was found to be a significant predictor of MACEs for only the very high-risk group, with an HR of 4.67 (95% CI 1.03-21.09; p = 0.045). The score demonstrated an AUC > 0.8, good discrimination (c-index > 0.8), and good calibration for predicting MACEs. However, it failed to achieve good performance for predicting MALEs and MALEs + MACEs. Based on all of the findings, CHA2DS2-VASc could potentially serve as a risk stratification score for predicting MACEs in patients with PAD, but it failed to qualify as a good predictor for MALEs.
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Objective: Considering the advantages and widespread presence of 3D-printing technology in surgical treatments, 3D-printed porous structure prostheses have been applied in a wide range of the treatments of bone tumor. In this research, we aimed to assess the application values of the 3D-printed custom prostheses with ultra-short stems for restoring bone defects and maintaining arthrosis in malignant bone tumors of lower extremities in children. Methods: Seven cases of pediatric patients were included in this study. In all cases, the prostheses were porous titanium alloy with ultra-short stems. MSTS 93 (Musculoskeletal Tumor Society) scores were recorded for the functional recovery of the limbs. VAS (Visual analogue scale) scores were utilized to assess the degree of painfulness for the patients. X-ray and MRI (magnetic resonance imaging) were applied to evaluate the bone integration, prostheses aseptic loosening, prostheses fracture, wound healing, and tumor recurrence during follow-up. Results: During follow-up, none of the patients developed any postoperative complications, including prostheses aseptic loosening, prostheses fracture, or tumor recurrence. Radiological examinations during the follow-up showed that prostheses implanted into the residual bone were stably fitted and bone defects were effectively reconstructed. The MSTS 93 scores were 24.9 ± 2.9 (20-28). VAS scores were decreased to 5.8 ± 1.2 (4.0-7.0). No statistically significant differences in leg length discrepancy were observed at the time of the last follow-up. Conclusion: 3D-printing technology can be effectively applied throughout the entire surgical treatment procedures of malignant bone tumors, offering stable foundations for the initial stability of 3D-printed prostheses with ultra-short stems through preoperative design, intraoperative precision operation, and personalized prosthesis matching. With meticulous postoperative follow-up, close monitoring of postoperative complications was ensured. These favorable outcomes indicate that the utilization of 3D-printed custom prostheses with ultra-short stems is a viable alternative for reconstructing bone defects. However, further investigation is warranted to determine the long-term effectiveness of the 3D-printing technique.
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Resuscitative endovascular balloon occlusion of the aorta (REBOA) is primarily utilized in traumatic noncompressible torso hemorrhage as a temporary approach to buying time until a definite intervention could be obtained. REBOA is mostly reported in inhospital or prehospital settings. Its interhospital transfer use remains controversial. In this report, we present a case with pelvic fracture and hemorrhagic shock who underwent REBOA placement and was transferred from a local hospital to a trauma center successfully for further surgical intervention.
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This study aimed to investigate the physicochemical properties of modified starch prepared through the simultaneous heat-moisture and phosphorylation treatment (HMPT) and osmotic pressure treatment (OPT) for water caltrop starch (WCS), mung bean starch (MBS), and amylose-rich corn starch (CS) for different time periods. Furthermore, variations in starch content [amylose and resistant starch (RS)], swelling powder (SP), water solubility index (WSI), crystallinity, thermal properties, gelatinization enthalpy (ΔH), and glycemic index (GI) were examined. This study demonstrates that neither HMPT nor OPT resulted in a significant increase in the resistant starch (RS) content, whereas all samples succeeded in heat-treating at 105⯰C for another 10â¯min exhibited a significant increase in RS content compared to their native counterparts. Moreover, the gelatinization temperatures of the three starches increased (To, Tp, and Tc), whereas their gelatinization enthalpy (ΔH) and pasting viscosity decreased. In particular, the GI of all three modified starches subjected to HMPT or OPT showed a decreasing trend with modification time, with OPT exhibiting the best effect. Therefore, appropriate modification through HMPT or OPT is a viable approach to develop MBS, WCS, and CS as processed foods with low GI requirements, which exceptionally may be suitable for canned foods, noodles, and bakery products.
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Calor , Presión Osmótica , Solubilidad , Almidón , Vigna , Agua , Zea mays , Zea mays/química , Almidón/química , Agua/química , Vigna/química , Fosforilación , Fenómenos Químicos , Amilosa/química , Amilosa/análisis , Viscosidad , Termodinámica , LythraceaeRESUMEN
Triboelectric nanogenerators (TENGs) have become reliable green energy harvesters by converting biomechanical motions into electricity. However, the inevitable charge leakage and poor electric field (EF) of conventional TENG result in inferior tribo-charge density on the active layer. In this paper, TiO2-MXene incorporated polystyrene (PS) nanofiber membrane (PTMx NFM) charge trapping interlayer is introduced into single electrode mode TENG (S-TENG) to prevent electron loss at the electrode interface. Surprisingly, this charge-trapping mechanism augments the surface charge density and electric output performance of TENGs. Polyvinylidene difluoride (PVDF) mixed polyurethane (PU) NFM is used as tribo-active layer, which improves the crystallinity and mechanical property of PVDF to prevent delamination during long cycle tests. Herein, the effect of this double-layer capacitive model is explained experimentally and theoretically. With optimization of the PTMx interlayer thickness, S-TENG exhibits a maximum open-circuit voltage of (280 V), short-circuit current of (20 µA) transfer charge of (120 nC), and power density of (25.2 µW cm-2). Then, this energy is utilized to charge electrical appliances. In addition, the influence of AC/DC EF simulation in wound healing management (vitro L929 cell migration, vivo tissue regeneration) is also investigated by changing the polarity of trans-epithelial potential (TEP) distribution in the wounded area.
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Background: The tumor microenvironment of cancers has emerged as a crucial component in regulating cancer stemness and plays a pivotal role in cell-cell communication. However, the specific mechanisms underlying these phenomena remain poorly understood. Methods: We performed the single-cell RNA sequencing (scRNA-seq) on nine HBV-associated hepatocellular carcinoma (HCC) patients. The heterogeneity of the malignant cells in pathway functions, transcription factors (TFs) regulation, overall survival, stemness, as well as ligand-receptor-based intercellular communication with macrophages were characterized. The aggressive and stemness feature for the target tumor subclone was validated by the conduction of in vitro assays including sphere formation, proliferation, Annexin V apoptosis, flow cytometry, siRNA library screening assays, and multiple in vivo preclinical mouse models including mouse hepatoma cell and human HCC cell xenograft models with subcutaneous or orthotopic injection. Results: Our analysis yielded a comprehensive atlas of 31,664 cells, revealing a diverse array of malignant cell subpopulations. Notably, we identified a stemness-related subclone of HCC cells with concurrent upregulation of CD24, CD47, and ICAM1 expression that correlated with poorer overall survival. Functional characterization both in vitro and in vivo validated S100A11 as one of the top downstream mediators for tumor initiation and stemness maintenance of this subclone. Further investigation of cell-cell communication within the tumor microenvironment revealed a propensity for bi-directional crosstalk between this stemness-related subclone and tumor-associated macrophages (TAMs). Co-culture study showed that this interaction resulted in the maintenance of the expression of cancer stem cell markers and driving M2-like TAM polarization towards a pro-tumorigenic niche. We also consolidated an inverse relationship between the proportions of TAMs and tumor-infiltrating T cells. Conclusions: Our study highlighted the critical role of stemness-related cancer cell populations in driving an immunosuppressive tumor microenvironment and identified the S100A11 gene as a key mediator for stemness maintenance in HCC. Moreover, our study provides support that the maintenance of cancer stemness is more attributed to M2 polarization than the recruitment of the TAMs.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Animales , Ratones , Carcinoma Hepatocelular/patología , Virus de la Hepatitis B , Neoplasias Hepáticas/patología , Macrófagos/metabolismo , Técnicas de Cocultivo , Línea Celular Tumoral , Microambiente TumoralRESUMEN
BACKGROUND: Serum AFP-L3%, AFP, and DCP are useful biomarkers for HCC detection, but their utility in assessing treatment response remains unknown. We aim to evaluate the accuracy of a biomarker model in the detection of posttreatment viable tumors. METHODS: For model derivation, recipients with HCC undergoing liver transplant from 2018 to 2022 who had biomarkers collected within 3 months before transplant were included. We developed a generalized linear model for detecting posttreatment viable tumors with the 3 biomarkers as covariates, which we termed the "LAD Score." An independent cohort of 117 patients with HCC was used for external validation. RESULTS: Among 205 recipients of transplant, 70.2% had evidence of viable tumor on explant. The median LAD score was higher among patients with viable versus nonviable tumors (1.06 vs. 0.465, p < 0.001). The LAD score had a sensitivity of 55.6% and a specificity of 85.1% at the cutoff of 0.927, which was more accurate than imaging for detecting posttreatment viable tumors (AUROC 0.736 vs. 0.643, respectively; p = 0.045). The superior performance of the LAD score over imaging is primarily driven by its greater accuracy in detecting tumors <2 cm in diameter (AUROC of the LAD score 0.721 vs. imaging 0.595, p = 0.02). In the validation data set, the LAD score had an AUROC of 0.832 (95% CI: 0.753, 0.911) with a sensitivity of 72.5% and a specificity of 89.4% at the cutoff of 0.927. CONCLUSIONS: Our findings suggest the utility of LAD score in treatment response assessment after locoregional therapy for HCC, particularly in detecting small tumors. A larger prospective study is in progress to validate its accuracy and evaluate its performance in recurrence monitoring.
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Biomarcadores de Tumor , Carcinoma Hepatocelular , Neoplasias Hepáticas , Trasplante de Hígado , alfa-Fetoproteínas , Humanos , Neoplasias Hepáticas/sangre , Neoplasias Hepáticas/cirugía , Neoplasias Hepáticas/terapia , Neoplasias Hepáticas/patología , Carcinoma Hepatocelular/sangre , Carcinoma Hepatocelular/cirugía , Carcinoma Hepatocelular/terapia , Carcinoma Hepatocelular/patología , Femenino , Masculino , Persona de Mediana Edad , Biomarcadores de Tumor/sangre , alfa-Fetoproteínas/análisis , Anciano , Resultado del Tratamiento , Sensibilidad y Especificidad , Estudios RetrospectivosRESUMEN
Genomic sequencing of clinical samples to identify emerging variants of SARS-CoV-2 has been a key public health tool for curbing the spread of the virus. As a result, an unprecedented number of SARS-CoV-2 genomes were sequenced during the COVID-19 pandemic, which allowed for rapid identification of genetic variants, enabling the timely design and testing of therapies and deployment of new vaccine formulations to combat the new variants. However, despite the technological advances of deep sequencing, the analysis of the raw sequence data generated globally is neither standardized nor consistent, leading to vastly disparate sequences that may impact identification of variants. Here, we show that for both Illumina and Oxford Nanopore sequencing platforms, downstream bioinformatic protocols used by industry, government, and academic groups resulted in different virus sequences from same sample. These bioinformatic workflows produced consensus genomes with differences in single nucleotide polymorphisms, inclusion and exclusion of insertions, and/or deletions, despite using the same raw sequence as input datasets. Here, we compared and characterized such discrepancies and propose a specific suite of parameters and protocols that should be adopted across the field. Consistent results from bioinformatic workflows are fundamental to SARS-CoV-2 and future pathogen surveillance efforts, including pandemic preparation, to allow for a data-driven and timely public health response.
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COVID-19 , SARS-CoV-2 , Humanos , SARS-CoV-2/genética , COVID-19/epidemiología , Pandemias , Flujo de Trabajo , Biología ComputacionalRESUMEN
OBJECTIVE@#To evaluate the efficacy of deep vein thrombosis (DVT) prevention among real-world surgical inpatients who received panax notoginseng saponins (PNS) combined with low-molecular-weight heparin (LMWH).@*METHODS@#A prospective cohort study was conducted among surgical patients between January 2016 and November 2018 in Xuanwu Hospital, Capital Medical University, Beijing, China. Participants received LMWH alone or PNS combined with LMWH for preventing DVT. The primary outcome was incidence of lower extremity DVT, which was screened once a week. Participants in the LMWH group were given LMWH (enoxaparin) via hypodermic injection, 4000-8000 AxalU once daily. Participants in the exposure group received PNS (Xuesaitong oral tablets, 100 mg, 3 times daily) combined with LMWH given the same as LMWH group.@*RESULTS@#Of the 325 patients screened for the study, 281 participants were included in the final analysis. The cohort was divided into PNS + LMWH group and LMWH group with 134 and 147 participants, respectively. There was a significant difference of DVT incidence between two groups (P=0.01), with 21 (15.7%) incident DVT in the PNS + LMWH group, and 41 (27.9%) incident DVT in the LMWH group. Compared with participants without DVT, the participants diagnosed with DVT were older and had higher D-dimer level. The multivariate logistic regression model showed a significant lower risk of incident DVT among participants in the PNS + LMWH group compared with the LMWH group (odds ratio 0.46, 95% confidence interval, 0.25-0.86). There were no significant differences in thromboelaslography values (including R, K, Angle, and MA) and differences in severe bleeding between two groups. No symptomatic pulmonary embolism occurred during the study.@*CONCLUSION@#Combined application of PNS and LMWH can effectively reduce the incidence of DVT among surgical inpatients compared with LMWH monotherapy, without increased risk of bleeding.
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Humanos , Anticoagulantes/uso terapéutico , Hemorragia , Heparina de Bajo-Peso-Molecular/uso terapéutico , Panax notoginseng , Estudios Prospectivos , Saponinas/uso terapéutico , Trombosis de la Vena/prevención & controlRESUMEN
@#AIM: To analyze the anatomical characteristics of nasolacrimal duct development in children with congenital nasolacrimal duct obstruction by nasolacrimal duct CT scan combined with three-dimensional reconstruction technology.<p>METHODS: Prospective case control study. Totally 84 children(84 eyes)with unilateral congenital nasolacrimal duct obstruction were treated in the Department of Ophthalmology of Baoding Children's Hospital from September 2018 to September 2020. The nasolacrimal duct CT scan combined with three-dimensional reconstruction was performed. The transverse diameter and anterior posterior diameter of bilateral nasolacrimal duct were measured, and the anatomical characteristics of nasolacrimal duct development were observed and analyzed. Paired <i>t</i>-test was performed on the transverse diameter and anteroposterior diameter of bilateral nasolacrimal duct.<p>RESULTS: Nasolacrimal duct CT scan combined with three-dimensional reconstruction can clearly show the anatomical characteristics of nasolacrimal duct development in children with congenital nasolacrimal duct obstruction. The transverse diameter of bony nasolacrimal duct was 4.63±0.92mm, anterior posterior diameter was 6.03±1.08mm, the transverse diameter of middle bony nasolacrimal duct was 4.02±0.88mm, anterior posterior diameter was 5.42±1.10mm, the transverse diameter of final bony nasolacrimal duct was 4.26±0.93mm, anterior posterior diameter was 5.66±1.02mm. The transverse diameter of the bony nasolacrimal duct in the initial segment of the contralateral side was 4.12±0.78mm, the anteroposterior diameter was 5.60±1.02mm, the transverse diameter of the bony nasolacrimal duct in the middle segment was 3.92±0.86mm, the anteroposterior diameter was 5.24±1.04mm, the transverse diameter of the bony nasolacrimal duct in the final segment was 4.30±0.98mm, the anteroposterior diameter was 5.52±1.04mm. The transverse diameter and anteroposterior diameter of the affected side were larger than those of the healthy side and enlarged(<i>P</i><0.01). There was no significant difference between the affected side and the healthy side(<i>P</i>>0.05).<p>CONCLUSION:The development of bony nasolacrimal duct in the affected side of congenital nasolacrimal duct obstruction is different from that in the healthy side. The initial segment of the affected side expanded obviously.
RESUMEN
@#AIM: To observe and analyze the therapeutic effect of fine training combined with virtual reality brain vision training in amblyopic children.<p>METHODS: Case control study. 232 cases(416 eyes)of amblyopia were diagnosed in Baoding children's Hospital for the first time. They were randomly divided into two groups. Group A was treated with fine training, while group B was treated with fine training combined with visual training. Duration of treatment was 6mo. The patients were followed up for 6mo. Objective to observe the clinical efficacy of amblyopia in children of different ages and degrees.<p>RESULTS: The total basic cure rate was 35.6%(74/208)in group A and 51.4%(107/208)in group B, which was higher than that in group A(<i>P<</i>0.01). The total effective rate was 80.8%(168/208)in group A, 91.3%(190/208)in group B, which was higher than that in group A(<i>P</i>=0.006). Therapeutic effect of each age group: the basic cure rates of group A were 55.9%(38/68), 34.9%(30/86), 11.1%(6/54)(<i>r</i>s=-0.76, <i>P<</i>0.01), respectively. The basic cure rates of group B were 70.6%(48/68), 54.6%(47/86), 22.2%(12/54)(<i>r</i>s=-0.78, <i>P<</i>0.01), respectively. The basic cure rate of group A and group B decreased with age. The effective rates of group A were 100%(68/68), 81.4%(70/86), 55.6%(30/54)(<i>r</i>s=-0.67, <i>P<</i>0.01), respectively. The effective rates of group B were 100%(68/68), 93.0%(80/86), 77.8%(42/54)(<i>r</i>s=-0.64, <i>P<</i>0.01), respectively. The efficiencies of A and B groups decreased with age. Therapeutic effect of amblyopia degree groups: the basic cure rates of group A were 63.3%(50/79), 25.0%(22/88)and 4.9%(2/41)(<i>r</i>s=-0.93, <i>P<</i>0.01), respectively. The basic cure rates of group B were 81.0%(64/79), 44.3%(39/88)and 9.8%(4/41),respectively(<i>r</i>s=-0.89, <i>P<</i>0.01). The basic cure rate of groups A and B was negatively correlated with the degree of amblyopia. The effective rates of group A were 83.5%(66/79), 79.5%(70/88), 78.0%(32/41)(<i>r</i>s=0.00, <i>P</i>=12.316), respectively. The effective rates of group B were 91.1%(72/79), 89.8%(79/88), 95.1%(39/41)(<i>r</i>s=0.00,<i> P</i>=15.603), respectively. There was no significant correlation between amblyopia severity and efficiency in groups A and B.<p>CONCLUSION: Fine training combined with virtual reality brain vision training is a safe and effective way to treat amblyopia. There is a certain correlation between the clinical efficacy and the age and the degree of amblyopia.