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Background: Autologous stem cell transplantation (ASCT) is a potentially curative strategy for relapse or refractory(r/r) aggressive lymphoma. However, a proportion of lymphoma patients who are at high risk of mobilization failure fail to mobilize stem cells and cannot proceed to ASCT. The aim of this study is to explore the efficacy and safety of Etoposide combined with Cytarabine (EA) plus G-CSF mobilization in poor mobilizers (PMs) with r/r aggressive lymphoma. Methods: This retrospective study analyzed the outcomes of chemo-mobilization based on EA (Etoposide 0.1 g/m2, qd d1~3; AraC 0.5 g/m2, q12h d1~3) in 98 patients with r/r aggressive lymphoma. Of these, 39 patients met the criteria for predicted PMs as proposed by the Gruppo Italiano Trapianto di Midollo Osseo working group. Results: Of the 39 PMs, 38(97.4%) patents harvested adequate mobilization (≥2×106 CD34+ cells/kg), while 31(79.5%) patients achieved optimal mobilization (≥5×106 CD34+ cells/kg). Overall, the mean number of CD34+ cells/kg collected was 17.99(range: 1.08~83.07) ×106 with an average of 1.4 apheresis sessions, and the number was 15.86(range: 0.37~83.07) ×106 for the first apheresis, respectively. A single apheresis procedure was sufficient to reach the target yield of adequate mobilization in 35(89.7%) PMs, while 76.9% of PMs achieved optimal collection within two apheresis sessions. We observed acceptable hematological toxicity and antibiotic usage exposure in 26 patients with a mean duration of 3.6 days. No grade 4 infection or mobilization-related mortality was recorded. Most patients underwent ASCT and achieved successful hematopoietic recovery with prompt engraftment duration, except for one NK/T-cell lymphoma patient who succumbed to severe septicemia after receiving conditioning chemotherapy. Conclusion: Our findings indicate that EA plus G-CSF is an effective and tolerable CD34+ stem cell mobilization strategy for patients with r/r lymphoma, including those predicted to be PMs. This regimen could be an option for patients with r/r lymphoma, particularly those undergoing mobilization for salvage ASCT therapy.
Subject(s)
Cytarabine , Etoposide , Granulocyte Colony-Stimulating Factor , Hematopoietic Stem Cell Mobilization , Lymphoma , Humans , Etoposide/administration & dosage , Etoposide/therapeutic use , Hematopoietic Stem Cell Mobilization/methods , Cytarabine/administration & dosage , Cytarabine/therapeutic use , Male , Female , Granulocyte Colony-Stimulating Factor/administration & dosage , Adult , Middle Aged , Lymphoma/therapy , Lymphoma/mortality , Lymphoma/drug therapy , Retrospective Studies , Aged , Young Adult , Hematopoietic Stem Cell Transplantation/methods , Transplantation, Autologous , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Recurrence , Treatment Outcome , AdolescentABSTRACT
Relapse remains the main cause of treatment failure in patients with myeloid malignancies even after allogeneic hematopoietic stem cell transplantation (allo-HSCT). We observed a particularly low incidence of relapse in patients prepared with fludarabine, busulfan and melphalan in our previous study and this multicenter retrospective analysis aimed to confirm the feasibility of the regimen and to identify the potential prognostic factors. This study was performed using registry data from adults patients with myeloid malignancies who underwent their first allo-HSCT following fludarabine(≥100 mg/m2), busulfan (≥3.2 mg/kg) and melphalan (≥100 mg/m2) based conditioning at nine transplantation centers in China between Jan. 2020 and Mar. 2022. A total of 221 consecutive patients (AML n = 171, MDS-IB-1 or 2 n = 44, CMML n = 6) with median age of 46 were enrolled in this study. The median follow-up was 507 days for survivors. The 2-year NRM, CIR, OS and DFS were 10.6% ± 2.2%, 14.8% ± 3.3%, 79.4% ± 3.7% and 74.6% ± 3.7%, respectively. In multivariate analyses, high HCT-CI (≥3) was the only independent factor for higher NRM [hazard ratio (HR), 2.96; 95% confidence interval (CI), 1.11 to 7.90; p = 0.030] and ECOG score ≥2 was the only independent factor for inferior OS (HR, 2.43; 95%CI, 1.15 to 5.16; p = 0.020) and DFS (HR, 2.12; 95%CI, 1.13 to 4.02; p = 0.020). AML diagnosis and positive measurable residual disease (MRD) at transplantation were predictors for higher CIR (HR = 7.92, 95%CI 1.05-60.03, p = 0.045; HR = 3.64, 95%CI 1.40-9.44, p = 0.008; respectively), while post-transplantation cyclophosphamide based graft-versus-host disease prophylaxis was associated with lower CIR (HR = 0.24 95%CI 0.11-0.54, p = 0.001). The intensity of conditioning regimen did not impact CIR, NRM, DFS and OS. These results supported that double alkylating agents of busulfan and melphalan based conditioning regimens were associated with low relapse rate and acceptable NRM in adult patients with myeloid malignancies. The optimal dose remained to be confirmed by further prospective studies.
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Gauze wound dressings have received considerable attention due to their cost-effectiveness, excellent mechanical properties, and widespread applications. However, their inability to actively combat microorganisms and effectively scavenge free radicals results in suboptimal wound management. In this study, a novel nonwoven-based gauze dressing coated with quaternized chitosan/tannic acid (QCS/TA), based on electrostatic interaction and hydrogen bonding, was successfully prepared using a spray-assisted layer-by-layer assembly method. The bio-based nonwoven dressing, assembled with multiple interlacing bilayers, demonstrated outstanding antimicrobial properties, eliminating 99.99 % of Staphylococcus aureus (S. aureus) and 85 % of Escherichia coli (E. coli). Compared to the pristine nonwoven dressing, the QCS/TA-coated nonwoven dressing scavenged >85 % of the surrounding radicals within 2 h. Additionally, the nonwoven dressing exhibits excellent coagulation properties. Notably, the facile spraying procedure preserved most of the softness and breathability of the nonwoven substrate. After the deposition of seven bilayers, the bending stiffness and drape coefficient increased by only 37.63 % and 3.85 %, respectively, while the air permeability and moisture permeability reached 1712 mm/s and 3683.58 g/m2/d, respectively. This bio-based nonwoven dressing, derived from safe and non-toxic ingredients, holds promise as the next generation of multifunctional gauze dressings.
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The fifth session of the 13th National People's Congress proposed to be committed to promoting carbon peaking and carbon neutrality, promoting the comprehensive green and low-carbon transformation of the economy and society and achieving high-quality development. As an important scientific and technological innovation and industrial cluster in Shaanxi Province, the economic development of the Xi'an Hi-tech Zone largely relies on energy consumption, making the task of carbon reduction particularly challenging. Firstly, taking the Xi'an Hi-tech Zone as the research object, through systematic accounting of carbon emissions within the park, we analyzed the current carbon emission status of enterprises in different energy types and industries. Then, using the Kaya model, multiple independent carbon peak scenarios were set up to predict the total carbon emissions and peak time under different scenarios. Finally, based on the development characteristics of the Xi'an Hi-tech Zone, we scientifically selected corresponding carbon emission reduction paths and provided reasonable emission reduction suggestions. The results showed that the proportion of carbon emissions consumed by electricity was currently the highest, and the share was increasing yearly. Industrial carbon emissions had always been dominant, and the development of the tertiary industry was becoming increasingly prosperous. In the scenario prediction, the carbon emission factor scenario, energy intensity scenario, and economic level scenario could reach the carbon peak by 2030. Among them, the economic development level had the greatest impact on the peak and time of the future carbon peak in the Xi'an Hi-tech Zone, whereas the industrial structure scenario, energy source structure scenario, and population size scenario had no peak before 2030. The future emission reduction path mainly started from decarbonization of the power sector, stable and high-quality economic development, green upgrading of energy and industrial structure, and building a green transportation system. This can reserve more preparation time for achieving carbon neutrality and provide decision-making reference for the low-carbon development of industrial parks in China.
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The pursuit of constructing humanoid robots to replicate the anatomical structures and capabilities of human beings has been a long-standing significant undertaking and especially garnered tremendous attention in recent years. However, despite the progress made over recent decades, humanoid robots have predominantly been confined to those rigid metallic structures, which however starkly contrast with the inherent flexibility observed in biological systems. To better innovate this area, the present work systematically explores the value and potential of liquid metals and their derivatives in facilitating a crucial transition towards soft humanoid robots. Through a comprehensive interpretation of bionics, an overview of liquid metals' multifaceted roles as essential components in constructing advanced humanoid robots-functioning as soft actuators, sensors, power sources, logical devices, circuit systems, and even transformable skeletal structures-is presented. It is conceived that the integration of these components with flexible structures, facilitated by the unique properties of liquid metals, can create unexpected versatile functionalities and behaviors to better fulfill human needs. Finally, a revolution in humanoid robots is envisioned, transitioning from metallic frameworks to hybrid soft-rigid structures resembling that of biological tissues. This study is expected to provide fundamental guidance for the coming research, thereby advancing the area.
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BACKGROUND: Although high-flow nasal cannula (HFNC) oxygenation is currently recommended to prevent desaturation during sedation for bronchoscopy, there is no consensus on an optimal flow rate. OBJECTIVE: To determine the optimal oxygen flow rate for HFNC to effectively prevent desaturation during sedation for bronchoscopy. DESIGN: Prospective, randomized, and controlled study. METHODS: Patients (n = 240) scheduled for bronchoscopy were randomized to receive HFNC with propofol sedation (fraction of inspired oxygen, 100%) at one of six flow rates of 10, 20, 30, 40, 50, and 60 L/min, designated as groups 1-6, respectively. RESULTS: The incidence of desaturation significantly decreased by increasing the oxygen flow rate (42.5%, 17.5%, 15%, 10%, 2.5%, and 0% for groups 1-6, respectively, p < 0.0001). The optimal oxygen flow rate for HFNC determined by probit regression to effectively prevent desaturation in 95% of patients was 43.20 (95% confidence interval, 36.43-55.96) L/min. The requirement for airway intervention was significantly decreased by increasing the oxygen flow rate. CONCLUSION: An HFNC flow rate of 50-60 L/min is recommended to prevent desaturation during sedation for bronchoscopy. REGISTRATION: NCT05298319 at ClinicalTrials.gov.
High-flow nasal cannula oxygenation during bronchoscopyMany patients undergo a special test to check their airways for problems. Sometimes, doctors need to take out a small part of the area that's causing trouble to find out what's wrong. But during this test, some patients can struggle to get enough oxygen, which can even be life-threatening. To help with this, there's a device called a high-flow nasal cannula (HFNC). It gives patients adjustable amounts of oxygen, like a gentle breeze into their nose. But doctors weren't sure how much oxygen was best during this test. So, we studied 240 patients using HFNC at different oxygen levelslike slow, medium, and fast flows. We found that the higher the oxygen flow, the less likely patients were to have oxygen problems. For example, at the lowest flow (10 liters per minute), about 42.5% of patients had oxygen trouble, but at the highest flow (60 liters per minute), none did. And we figured out that a flow rate around 43.2 liters per minute would prevent 95% patients from having oxygen problems. So, we recommend using a flow rate between 50 and 60 liters per minute during this test to keep patients safe from oxygen issues.
Subject(s)
Bronchoscopy , Cannula , Oxygen Inhalation Therapy , Propofol , Humans , Bronchoscopy/adverse effects , Male , Prospective Studies , Female , Middle Aged , Oxygen Inhalation Therapy/methods , Aged , Propofol/administration & dosage , Propofol/adverse effects , Oxygen/administration & dosage , Hypnotics and Sedatives/administration & dosage , Conscious Sedation , Treatment Outcome , AdultABSTRACT
Ruptured dissecting aneurysms in posterior intracranial circulation present significant clinical challenges and often cause poor prognoses. Our cohort used overlapping stents as the primary treatment. We analyzed the medical records of 27 patients (18 men/nine women) with ruptured posterior circulation dissecting aneurysms (PCDAs). Their average age was 52 years. We selected 11 patients who used Enterprise (EP) and LVIS stents overlappingly and matched them 1:1 with counterparts who received either EP or LVIS stents individually. Overlapping stents was a feasible treatment in all 27 cases. We successfully followed up 26 patients for ≥6 months. Regrettably, one patient died from intracranial hypertension on Day 7 post-procedure. Immediate post-procedure angiographies indicated Raymond grade I, II, and III occlusions of PCDAs in 16 (59.3%), 7 (25.9%), and 4 (14.8%) cases, respectively. At an average follow-up duration of 16.2 months, 25 patients (96.2%) had modified Rankin Scale scores of 0-2, signifying positive outcomes. One patient (3.8%) had a score of 3-4. Recurrence rates for the EP and LVIS stent groups were higher than those of the overlapping stent group (45.45% vs. 9.09%, p = 0.15 and 27.27% vs. 9.09%, p = 0.59, respectively). No significant difference in recurrence rates existed between the overlapping and single-stent groups. Similarly, follow-up outcomes were consistent between the two groups. Overlapping stents could be an efficient method for treating ruptured PCDAs.
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Glasses, unlike crystals, are intrinsically brittle due to the absence of microstructure-controlled toughening, creating fundamental constraints for their technological applications. Consequently, strategies for toughening glasses without compromising their other advantageous properties have been long sought after but elusive. Here we report exceptional toughening in oxide glasses via paracrystallization, using aluminosilicate glass as an example. By combining experiments and computational modelling, we demonstrate the uniform formation of crystal-like medium-range order clusters pervading the glass structure as a result of paracrystallization under high-pressure and high-temperature conditions. The paracrystalline oxide glasses display superior toughness, reaching up to 1.99 ± 0.06 MPa m1/2, surpassing any other reported bulk oxide glasses, to the best of our knowledge. We attribute this exceptional toughening to the excitation of multiple shear bands caused by a stress-induced inverse transformation from the paracrystalline to amorphous states, revealing plastic deformation characteristics. This discovery presents a potent strategy for designing highly damage-tolerant glass materials and emphasizes the substantial influence of atomic-level structural variation on the properties of oxide glasses.
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Arsenic contamination in drinking water causes a global public health problem. Emerging evidence suggests that arsenic may act as an environmental risk factor for anxiety disorders. However, the exact mechanism underlying the adverse effects has not been fully elucidated. This study aimed to evaluate the anxiety-like behaviors of mice exposed to arsenic trioxide (As2O3), to observe the neuropathological changes, and to explore the link between the GABAergic system and behavioral manifestations. For this purpose, male C57BL/6 mice were exposed to various doses of As2O3 (0, 0.15, 1.5, and 15 mg/L) through drinking water for 12 weeks. Anxiety-like behaviors were assessed using the open field test (OFT), light/dark choice test, and elevated zero maze (EZM). Neuronal injuries in the cerebral cortex and hippocampus were assessed by light microscopy with H&E and Nissl staining. Ultrastructural alteration in the cerebral cortex was assessed by transmission electron microscope (TEM). The expression levels of GABAergic system-related molecules (i.e., glutamate decarboxylase, GABA transporter, and GABAB receptor subunits) in the prefrontal cortex (PFC) were determined by qRT-PCR and western blotting. Arsenic exposure showed a striking anxiogenic effect on mice, especially in the group exposed to 15 mg/L As2O3. Light microscopy showed neuron necrosis and reduced cell counts. TEM revealed marked ultrastructural changes, including the vacuolated mitochondria, disrupted Nissl bodies, an indentation in the nucleus membrane, and delamination of myelin sheath in the cortex. In addition, As2O3 influenced the GABAergic system in the PFC by decreasing the expression of the glutamate decarboxylase 1 (GAD1) and the GABAB2 receptor subunit, but not the GABAB1 receptor subunit. To sum up, sub-chronic exposure to As2O3 is associated with increased anxiety-like behaviors, which may be mediated by altered GABAergic signaling in the PFC. These findings shed light on the mechanisms responsible for the neurotoxic effects of arsenic and therefore more cautions should be taken.
Subject(s)
Arsenic , Drinking Water , Male , Mice , Animals , Arsenic/toxicity , Mice, Inbred C57BL , Prefrontal Cortex/metabolism , Prefrontal Cortex/pathology , Anxiety/chemically induced , gamma-Aminobutyric Acid/metabolismABSTRACT
Leaf senescence is an integral step in the final stages of plant development, as nutrient remobilization from leaves to sink organs is accomplished during this process. NACs compose a large superfamily of plant-specific TFs involved in multiple plant development processes. Here, we identified a maize NAC TF, ZmNAC132, involved in leaf senescence and male fertility. ZmNAC132 expression was tightly linked to leaf senescence in an age-dependent manner. Knockout of ZmNAC132 led to delays in chlorophyll degradation and leaf senescence, whereas overexpression of ZmNAC132 had the opposite effects. ZmNAC132 could bind to and transactivate the promoter of ZmNYE1, a major chlorophyll catabolic gene, to accelerate chlorophyll degradation during leaf senescence. Moreover, ZmNAC132 affected male fertility through the upregulation of ZmEXPB1, an expansin-encoding gene associated with sexual reproduction and other related genes. Together, the results show that ZmNAC132 participates in the regulation of leaf senescence and male fertility through the targeting of different downstream genes in maize.
Subject(s)
Transcription Factors , Zea mays , Transcription Factors/genetics , Transcription Factors/metabolism , Zea mays/genetics , Zea mays/metabolism , Plant Senescence , Gene Expression Regulation, Plant , Chlorophyll/metabolism , Fertility/genetics , Plant Leaves/metabolism , Plant Proteins/genetics , Plant Proteins/metabolismABSTRACT
Increasing incidence of skin aging has highlighted the importance of identifying effective drugs with repurposed opportunities for skin aging. We aimed to identify pharmaco-active compounds with drug-repurposing opportunities for skin aging from Angelica acutiloba (Siebold & Zucc.) Kitag. (AAK). The proximity of network medicine framework (NMF) firstly identified 8 key AAK compounds with repurposed opportunities for skin aging, which may exert by regulating 29 differentially expressed genes (DGEs) of skin aging, including 13 up-regulated targets and 16 down-regulated targets. Connectivity MAP (cMAP) analysis revealed 8 key compounds were involved in regulating the process of cell proliferation and apoptosis, mitochondrial energy metabolism and oxidative stress of skin aging. Molecular docking analysis showed that 8 key compounds had a high docked ability with AR, BCHE, HPGD and PI3, which were identified as specific biomarker for the diagnosis of skin aging. Finally, the mechanisms of these key compounds were predicted to be involved in inhibiting autophagy pathway and activating Phospholipase D signaling pathway. In conclusion, this study firstly elucidated the drug-repurposing opportunities of AAK compounds for skin aging, providing a theoretical reference for identifying repurposing drugs from Chinese medicine and new insights for our future research.
Subject(s)
Angelica , Skin Aging , Angelica/metabolism , Drug Repositioning , Molecular Docking Simulation , Signal TransductionABSTRACT
Background: Hepatocellular carcinoma (HCC), one of the most common cancers worldwide, exhibits high immune heterogeneity and mortality. Emerging studies suggest that copper (Cu) plays a key role in cell survival. However, the relationship between Cu and tumor development remains unclear. Methods: We investigated the effects of Cu and cuproptosis-related genes (CRGs) in patients with HCC in the TCGA-LIHC (The Cancer Genome Atlas-Liver cancer, n = 347) and ICGC-LIRI-JP (International Cancer Genome Consortium-Liver Cancer-Riken-Japan, n = 203) datasets. Prognostic genes were identified by survival analysis, and a least absolute shrinkage and selection operator (Lasso) regression model was constructed using the prognostic genes in the two datasets. Additionally, we analyzed differentially expressed genes and signal pathway enrichment. We also evaluated the effects of CRGs on tumor immune cell infiltration and their co-expression with immune checkpoint genes (ICGs) and performed validation in different tumor immune microenvironments (TIMs). Finally, we performed validation using clinical samples and predicted the prognosis of patients with HCC using a nomogram. Results: A total of 59 CRGs were included for analysis, and 15 genes that significantly influenced the survival of patients in the two datasets were identified. Patients were grouped by risk scores, and pathway enrichment analysis suggested that immune-related pathways were substantially enriched in both datasets. Tumor immune cell infiltration analysis and clinical validation revealed that PRNP (Prion protein), SNCA (Synuclein alpha), and COX17 (Cytochrome c oxidase copper chaperone COX17) may be closely correlated with immune cell infiltration and ICG expression. A nomogram was constructed to predict the prognosis of patients with HCC using patients' characteristics and risk scores. Conclusion: CRGs may regulate the development of HCC by targeting the TIM and ICGs. CRGs such as PRNP, SNCA, and COX17 could be promising targets for HCC immune therapy in the future.
Subject(s)
Apoptosis , Carcinoma, Hepatocellular , Liver Neoplasms , Humans , Biomarkers , Carcinoma, Hepatocellular/genetics , Copper , Genes, Regulator , Liver Neoplasms/genetics , Tumor Microenvironment/geneticsABSTRACT
Background: Phosphoinositide 3-kinases (PI3Ks) are lipid enzymes that regulate a wide range of intracellular functions. In contrast to Class I and Class III PI3K, which have more detailed descriptions, Class II PI3K has only recently become the focus of functional research. PIK3C2A is a classical member of the PI3Ks class II. However, the role of PIK3C2A in cancer prognosis and progression remains unknown. Methods: The expression pattern and prognostic significance of PIK3C2A in human malignancies were investigated using multiple datasets and scRNA-seq data. The PIK3C2A expression in renal clear cell carcinoma (KIRC) was then validated utilizing Western blot. The functional role of PIK3C2A in KIRC was assessed using combined function loss experiments with in vitro experiments. Furthermore, the correlation of PIK3C2A expression with tumor immunity was investigated in KIRC. The TCGA database was employed to investigate PIK3C2A functional networks. Results: Significant decrease in PIK3C2A expression in KIRC, demonstrated that it potentially influences the prognosis of diverse tumors, particularly KIRC. In addition, PIK3C2A was significantly correlated with the T stage, M stage, pathologic stage, and histologic grade of KIRC. Nomogram models were constructed and used to predict patient survival based on the results of multivariate Cox regression analysis. PIK3C2A knockdown resulted in significantly increased KIRC cell proliferation. Of note, PIK3C2A expression demonstrated a significant correlation with the infiltrating levels of primary immune cells in KIRC. Conclusion: These findings support the hypothesis that PIK3C2A is a novel biomarker for tumor progression and indicates dynamic shifts in immune infiltration in KIRC. Furthermore, aberrant PIK3C2A expression can influence the biological activity of cancer cells.
Subject(s)
Carcinoma, Renal Cell , Kidney Neoplasms , Humans , Prognosis , Carcinoma, Renal Cell/genetics , Blotting, Western , Kidney Neoplasms/genetics , Kidney , Phosphatidylinositol 3-Kinases/geneticsABSTRACT
Phloretin (Phl) is a natural flavonoid compound with wide range of biological activities but demonstrates poor water solubility and limited pharmacological effects. In this study, one cocrystal of phloretin-isoniazid (Phl-Inz) was prepared successfully using the solvent evaporation method. The physical properties of cocrystal were characterized by differential scanning calorimetry (DSC), thermogravimetric analysis (TG), powder X-ray diffraction (PXRD), Fourier-transform infrared (FT-IR) and single crystal X-ray diffraction (SCXRD). The Hirshfeld surface analysis explained further interactions in the cocrystal. The solubility test showed that the solubility of the cocrystal was increased at pH 1.2 and pH 6.8 compared to that of the pure drug. The test in vitro simulated gastrointestinal digestion showed that the release of phloretin in the cocrystal was better than that in the pure phloretin. The results of the DPPH and ABTS scavenging activity showed that the in vitro antioxidant activity of the cocrystal was improved. The anticancer assay exhibited improved cytotoxicity in the Phl-Inz cocrystal as compared with the pure Phl.
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Background/purpose: Over-dependence on existing synthetic scaffolds and insufficient osteoinductive and vasculogenic growth factors have limited the development of bone regeneration. The study aimed to assess the feasibility of using marrow-derived mesenchymal stem cells (BMSCs) cell sheets co-expressing bone morphogenetic proteins 2 (BMP2) and vascular endothelial growth factor (VEGF) for repairing critical-sized calvarial defects. Materials and methods: BMSCs cell sheets were genetically engineered to express BMP2/VEGF alone or together. Alterations in osteogenic markers were examined by quantitative real-time PCR (qRT-PCR) and western blotting. A critical-sized calvarial bone defect model was used to investigate the osteogenesis effects of BMP2/VEGF cell sheets alone or in combination. The efficacy was assessed with micro-computed tomography (micro-CT) and histology. Results: In vitro, the expression of BMP2 and VEGF through lentiviral transduction was confirmed by qRT-PCR and western blotting against BMP2 and VEGF. Lentiviral delivery of BMP2 and VEGF resulted in the upregulation of osteogenic markers. In vivo, in a critical-sized calvarial bone defect model, 3D-reconstructed micro-CT images revealed that treatment of the calvarial defects with the BMP2/VEGF cell sheet resulted in significantly greater amounts of newly formed bone at 8 weeks after surgery than treatment with cell sheets with single gene transduction or vehicle controls. The results were confirmed by histological assessment by H&E staining and Masson staining. Conclusion: This study demonstrates that BMP2/VEGF co-expressing BMSCs sheets promote bone regeneration in critical-sized calvarial bone defects. The BMP2/VEGF cell sheets provide a functional bioactive scaffold for critical-size bone reconstruction.
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BACKGROUND: The current neck management for early oral squamous cell carcinoma (OSCC) has always been a controversial issue. A comprehensive model is necessary for predicting an individual's metastasis risk and appropriate patient counseling. METHODS: A nomogram for predicting 2-year LNM in patients with cT1-2N0 OSCC was developed and validated using clinicopathological data from 642 patients from 2000 to 2018 in four hospitals, China. RESULTS: Three variables (pathology grade, depth of invasion, tumor-infiltrating lymphocytes) were included in nomogram. C-indices were 0.826 (95% CI: 0.786-0.866) and 0.726 (95% CI: 0.653-0.780) in the internal and external validation. Kaplan-Meier method found the 2-year LNM rate of high-risk group (35.8%) was much higher than that of the low-risk group (14.5%). The nomogram model has an advantage over the 8th AJCC TNM stage in predicting the individual 2-year LNM probability for early OSCC. CONCLUSION: Patients with low-risk nomogram score may receive neck observation; those with high-risk score should receive END.
Subject(s)
Carcinoma, Squamous Cell , Head and Neck Neoplasms , Mouth Neoplasms , Humans , Lymphatic Metastasis , Mouth Neoplasms/surgery , Mouth Neoplasms/pathology , Carcinoma, Squamous Cell/surgery , Carcinoma, Squamous Cell/pathology , Squamous Cell Carcinoma of Head and Neck/surgery , Nomograms , Risk FactorsABSTRACT
OBJECTIVE: The objectives of this study were to estimate the prognostic value of the tumour-stroma ratio (TSR) and tumour budding (TB) in oral tongue squamous cell carcinoma (OTSCC) and to establish a reliable model to predict the outcome of OTSCC patients. METHODS: A total of 103 patients surgically treated at our hospital were enrolled in this study. Chi-square tests, Kaplan-Meier analyses and Cox proportional hazards regression models were performed for statistical analysis. RESULTS: Fifty-six patients were categorized as stroma-rich, and 47 patients were categorized as stroma-poor. Only pathological grade was associated with the TSR (p = 0.017). Kaplan-Meier analysis showed that stroma-rich, high-intensity budding and high risk groups were associated with worse prognosis. The Cox regression model showed that the TSR was an independent risk factor for OTSCC patients prognosis, and the high risk group was also related to poor prognosis (p < 0.05). TB was significantly associated with poor prognosis but was not an independent risk factor. CONCLUSIONS: We found that patients in the stroma-rich group had a worse long-term prognosis. The TSR is an independent risk factor for OTSCC patients' outcome. In addition, a risk model that combined the TSR and TB proved to be valuable for predicting OTSCC patients' outcome.
Subject(s)
Carcinoma, Squamous Cell , Head and Neck Neoplasms , Tongue Neoplasms , Humans , Prognosis , Squamous Cell Carcinoma of Head and Neck/pathology , Carcinoma, Squamous Cell/surgery , Carcinoma, Squamous Cell/pathology , Tongue Neoplasms/surgery , Tongue Neoplasms/pathology , Retrospective Studies , Head and Neck Neoplasms/pathology , Neoplasm StagingABSTRACT
Smilax glabra Roxb (SGR) has been widely applied alone or in combination with other Chinese herbs in heart failure (HF), but its mechanism and protective effect have not been investigated. We aimed to explore the mechanism and protective effect of SGR on the treatment of HF. Network pharmacology analysis predicted that SGR was involved in the regulation of cell proliferation, oxidation-reduction process, apoptotic process, ERK1 and ERK2 cascade, MAPK cascade, etc. Its mechanism was mainly involved in the MAPK signaling pathway, calcium signaling pathway, cardiac muscle contraction, etc. Subsequently, SGR was proved to improve cellular viability, restore cellular morphology, suppress cellular and mitochondrial ROS production, improve H2O2-induced lysosome inhibition, attenuate mitochondrial dysfunction, and protect mitochondrial respiratory and energy metabolism in H9c2 cells. SGR activated the p38MAPK pathway by decreasing the mRNA expression of AKT, PP2A, NF-KB, PP2A, RAC1, and CDC42 and increasing the mRNA expression of Jun, IKK, and Sirt1. SGR also decreased the protein expression of ERK1, ERK2, JNK, Bax, and Caspase3 and increased the protein expression of p38MAPK and Bcl-2. In addition, Istidina at the highest degree was identified in SGR via the UHPLCLTQ-Orbitrap-MSn method, and it was suggested as anti-heart failure agents by targeting SRC with molecular docking analysis. In conclusion, SGR has a protective effect on HF through cellular and mitochondrial protection via multi-compounds and multi-targets, and its mechanism is involved in activating the p38 MAPK pathway. Istidina may be possible anti-HF agents by targeting SRC.
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To improve the ability of remote sensing technology in recognizing black-odorous water bodies in Hangzhou, this study analyzed the typical spectral characteristics of black-odorous water in Hangzhou based on measured spectral data and water quality parameters, including the transparency, dissolved oxygen, oxidation reduction potential, and ammonia nitrogen. The single-band threshold method, the normalized difference black-odorous water index (NDBWI) model, the black-odorous water index (BOI) model, and the color purity on a Commission Internationale de L'Eclairage (CIE) model were compared to analyze the spatial and temporal distribution characteristics of the black-odorous water in Hangzhou. The results showed that: (1) The remote sensing reflectance of black-odorous water was lower than that of ordinary water, the spectral curve was gentle, and the wave peak shifted toward the near-infrared direction in the wavelength range of 650-850 nm; (2) Among the aforementioned models, the normalized and improved normalized black-odorous water index methods had a higher accuracy, reaching 87.5%, and the threshold values for black-odorous water identification were 0.14 and 0.1, respectively; (3) From 2015 to 2018, the quantity of black-odorous water in the main urban area of Hangzhou showed a decreasing trend, and black-odorous water was mainly distributed in the Gongshu District and tended to appear in narrow rivers, densely populated areas, and factory construction sites. This study is expected to be of great practical value for the rapid tracking and monitoring of urban black-odorous water by using remote sensing technology for future work.