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Endovascular treatment (EVT) using stents has become the primary option for severe cerebrovascular stenosis. However, considerable challenges remain to be addressed, such as in-stent restenosis (ISR) and late thrombosis. Many modified stents have been developed to inhibit the hyperproliferation of vascular smooth muscle cells (SMCs) and protect vascular endothelial cells (VECs), thereby reducing such complications. Some modified stents, such as those infused with rapamycin, have improved in preventing acute thrombosis. However, ISR and late thrombosis, which are long-term complications, remain unavoidable. Panax notoginseng saponin (PNS), a traditional Chinese medicine consisting of various compounds, is beneficial in promoting the proliferation and migration of VECs and inhibiting the proliferation of SMCs. Herein, a 3D-printed polycaprolactone (PCL) stent loaded with PNS (PNS-PCL stent) was developed based on a previous study. In vitro studies confirmed that PNS promotes the migration and proliferation of VECs, which were damaged, by increasing the expression levels of microRNA-126, p-AKT, and endothelial nitric oxide synthase. In vivo, the PNS-PCL stents maintained the patency of the carotid artery in rabbits for up to three months, outperforming the PCL stents. The PNS-PCL stents may present a new solution for the EVT of cerebrovascular atherosclerotic stenosis in the future.
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Background: Tumor necrosis (TN) is a common feature in lung squamous cell carcinoma (LSCC), which could provide useful predictive and prognostic information. Objectives: This study aimed to investigate the effect of pretreatment pulmonary TN (PTN) on the prognosis of first-line anti-programmed cell death 1 (PD-1)/PD ligand 1 (PD-L1) inhibitor in advanced LSCC. Design: We conducted a retrospective study to analyze the association between the presence of PTN and clinical outcomes in advanced LSCC patients treated with anti-PD-1/PD-L1 inhibitors. Methods: Data from 240 eligible patients were collected from 27 hospitals across China between 2016 and 2020. The presence of PTN was assessed using contrast-enhanced chest computed tomography (CT) imaging at baseline. We utilized the Cox proportional-hazards regression model to analyze the association between PTN and clinical outcomes. In addition, to account for potential confounding factors and ensure comparability between groups, we employed propensity score-matching (PSM) analysis. Results: In the overall patient cohort, the presence of PTN was 39.6%. The median follow-up duration was 20.3 months. The positive PTN group exhibited a notably inferior median progression-free survival (PFS; 6.5 months vs 8.6 months, p = 0.012) compared to the negative PTN group. Within the Cox proportional-hazards regression model, PTN emerged as an independent predictor of unfavorable PFS (hazard ratio (HR) = 1.354, 95% confidence interval (CI): 1.002-1.830, p = 0.049). After PSM, the median PFS for the positive PTN group (6.5 months vs 8.0 months, p = 0.027) remained worse than that of the negative PTN group. Multivariate analyses also further underscored that the presence of PTN independently posed a risk for shorter PFS (HR = 1.494, 95% CI: 1.056-2.112, p = 0.023). However, no statistically significant difference in overall survival was observed between the two groups. Conclusion: Our study suggests that the presence of PTN on baseline contrast-enhanced chest CT is a potential negative prognostic imaging biomarker for the outcome of anti-PD-1/PD-L1 inhibitor therapy in advanced LSCC. Further studies are warranted to validate these findings and explore the underlying mechanisms.
Predicting anti-PD-1/PD-L1 inhibitor treatment outcomes: pulmonary tumor necrosis in lung squamous cell carcinoma Our study focused on lung squamous cell carcinoma (LSCC) patients receiving first-line anti-PD-1/PD-L1 therapy. We explored the impact of a feature called pretreatment pulmonary tumor necrosis (PTN) on their prognosis. PTN was identified in 39.6% of patients using baseline chest CT scans. Results revealed that patients with PTN had a shorter time without disease progression (median PFS of 6.5 months compared to 8.6 months) and a higher risk of unfavorable outcomes. This suggests that PTN may serve as a negative prognostic imaging marker for anti-PD-1/PD-L1 therapy in advanced LSCC. Further research is needed to confirm and understand these findings better.
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To solve the problems of slow regeneration and mismatch of axon regeneration after peripheral nerve injury, nerve guidance conduits (NGCs) have been widely used to promote nerve regeneration. Multichannel NGCs have been widely studied to mimic the structure of natural nerve bundles. However, multichannel conduits are prone to structural instability. Thermo-responsive shape memory polymers (SMPs) can maintain a persistent initial structure over the body temperature range. Electrical stimulation (ES), utilized within nerve NGCs, serves as a biological signal to expedite damaged nerve regeneration. Here, an electrospun shape-persistent conductive NGC is designed to maintain the persistent tubular structure in the physiological temperature range and improve the conductivity. The physicochemical and biocompatibility of these P, P/G, P/G-GO, and P/G-RGO NGCs are conducted in vitro. Meanwhile, to evaluate biocompatibility and peripheral nerve regeneration, NGCs are implanted in subcutaneous parts of the back of rats and sciatic nerves assessed by histology and immunofluorescence analyses. The conductive NGC displays a stable structure, good biocompatibility, and promoted nerve regeneration. Collectively, the shape-persistent conductive NGC (P/G-RGO) is expected to promote peripheral nerve recovery, especially for long-gap and large-diameter nerves.
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Background: Small-diameter vascular grafts have become the focus of attention in tissue engineering. Thrombosis and aneurysmal dilatation are the two major complications of the loss of vascular access after surgery. Therefore, we focused on fabricating 3D printed electrospun vascular grafts loaded with tetramethylpyrazine (TMP) to overcome these limitations. Methods: Based on electrospinning and 3D printing, 3D-printed electrospun vascular grafts loaded with TMP were fabricated. The inner layer of the graft was composed of electrospun poly(L-lactic-co-caprolactone) (PLCL) nanofibers and the outer layer consisted of 3D printed polycaprolactone (PCL) microfibers. The characterization and mechanical properties were tested. The blood compatibility and in vitro cytocompatibility of the grafts were also evaluated. Additionally, rat abdominal aortas were replaced with these 3D-printed electrospun grafts to evaluate their biosafety. Results: Mechanical tests demonstrated that the addition of PCL microfibers could improve the mechanical properties. In vitro experimental data proved that the introduction of TMP effectively inhibited platelet adhesion. Afterwards, rat abdominal aorta was replaced with 3D-printed electrospun grafts. The 3D-printed electrospun graft loaded with TMP showed good biocompatibility and mechanical strength within 6 months and maintained substantial patency without the occurrence of acute thrombosis. Moreover, no obvious aneurysmal dilatation was observed. Conclusions: The study demonstrated that 3D-printed electrospun vascular grafts loaded with TMP may have the potential for injured vascular healing.
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Biodegradable stents are considered a promising strategy for the endovascular treatment of cerebrovascular diseases. The visualization of biodegradable stents is of significance during the implantation and long-term follow-up. Endowing biodegradable stents with X-ray radiopacity can overcome the weakness of intrinsic radioparency of polymers. Hence, this work focuses on the development of an entirely X-ray visible biodegradable stent (PCL-KIO3) composed of polycaprolactone (PCL) and potassium iodate via physical blending and 3D printing. The in vitro results show that the introduction of potassium iodate makes the 3D-printed PCL stents visualizable under X-ray. So far, there is inadequate study about polymeric stent visualization in vivo. Therefore, PCL-KIO3 stents are implanted into the rabbit carotid artery to evaluate the biosafety and visibility performance. During stent deployment, the visualization of the PCL-KIO3 stent effectively helps to understand the position and dilation status of stents. At 6-month follow-up, the PCL-KIO3 stent could still be observed under X-ray and maintains excellent vessel patency. To sum up, this study demonstrates that PCL-KIO3 stent may provide a robust strategy for biodegradable stent visualization.
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Implantes Absorbibles , Arterias Carótidas , Poliésteres , Impresión Tridimensional , Stents , Animales , Conejos , Poliésteres/química , Arterias Carótidas/cirugía , Rayos XRESUMEN
AIMS: To investigate the predictive value of baseline C-reactive protein (CRP) levels on the efficacy of chemotherapy plus immune checkpoint inhibitors (ICI) in patients with advanced lung squamous cell carcinoma (LSCC). MATERIALS AND METHODS: In this retrospective multicenter study spanning from January 2016 to December 2020, advanced LSCC patients initially treated with chemotherapy or a combination of chemotherapy and ICI were categorized into normal and elevated CRP subgroups. The relationship between CRP levels and treatment outcomes was analyzed using multivariate Cox proportional hazards models and multivariate logistic regression, focusing primarily on the progression-free survival (PFS) endpoint, and secondarily on overall survival (OS) and objective response rate (ORR) endpoints. Survival curves were generated using the Kaplan-Meier method, with the log-rank test used for comparison between groups. RESULTS: Of the 245 patients evaluated, the 105 who received a combination of chemotherapy and ICI with elevated baseline CRP levels exhibited a significant reduction in PFS (median 6.5 months vs. 11.8 months, HR, 1.78; 95% CI: 1.12-2.81; p = 0.013) compared to those with normal CRP levels. Elevated CRP was identified as an independent risk factor for poor PFS through multivariate-adjusted analysis. However, among the 140 patients receiving chemotherapy alone, baseline CRP levels did not significantly influence PFS. Furthermore, within the combination therapy group, there was a notable decrease in the ORR (51% vs. 71%, p = 0.035), coupled with a significantly shorter OS (median 20.9 months vs. 31.5 months, HR, 2.24; 95% CI: 1.13-4.44; p = 0.033). CONCLUSION: In patients with advanced LSCC, elevated baseline CRP levels were identified as an independent predictive factor for the efficacy of combination therapy with chemotherapy and ICI, but not in chemotherapy alone. This suggests that CRP may be a valuable biomarker for guiding treatment strategies.
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Carcinoma de Pulmón de Células no Pequeñas , Carcinoma de Células Escamosas , Neoplasias Pulmonares , Humanos , Proteína C-Reactiva , Inhibidores de Puntos de Control Inmunológico/farmacología , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Estudios Retrospectivos , Carcinoma de Células Escamosas/tratamiento farmacológico , Neoplasias Pulmonares/tratamiento farmacológico , PulmónRESUMEN
BACKGROUND: BAT1706 is a proposed biosimilar of bevacizumab (Avastin®). We aimed to compare the efficacy and safety of BAT1706 with that of EU-sourced reference bevacizumab (EU-bevacizumab) in patients with advanced nonsquamous non-small cell lung cancer (NSCLC). METHODS: Patients were randomized 1:1 to BAT1706 plus paclitaxel and carboplatin (BAT1706 arm) or EU-bevacizumab plus paclitaxel and carboplatin (EU-bevacizumab arm) given every 3 weeks for six cycles, followed by maintenance therapy with BAT1706 or EU-bevacizumab. The primary endpoint was overall response rate at week 18 (ORR18 ). Clinical equivalence was demonstrated if the 90% confidence interval (CI) of the BAT1706:EU-bevacizumab ORR18 risk ratio was contained within the predefined equivalence margins of 0.75-1.33 (China National Medical Products Administration requirements), or 0.73-1.36 (US Food and Drug Administration), or if the 95% CI of the ORR18 risk difference between treatments was contained within the predefined equivalence margin of -0.12 to 0.15 (EMA requirements). RESULTS: In total, 649 randomized patients (BAT1706, n = 325; EU-bevacizumab, n = 324) received at least one cycle of combination treatment. The ORR18 was comparable between the BAT1706 and EU-bevacizumab arms (48.0% and 44.5%, respectively). The ORR18 risk ratio of 1.08 (90% CI: 0.94-1.24) and the ORR18 risk difference of 0.03 (95% CI: -0.04 to 0.11) were within the predefined equivalence margins, demonstrating the biosimilarity of BAT1706 and EU-bevacizumab. The safety profile of BAT1706 was consistent with that of EU-bevacizumab and no new safety signals were observed. CONCLUSION: In patients with advanced nonsquamous NSCLC, BAT1706 demonstrated clinical equivalence to EU-bevacizumab in terms of efficacy, safety, pharmacokinetics, and immunogenicity.
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Biosimilares Farmacéuticos , Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Humanos , Protocolos de Quimioterapia Combinada Antineoplásica , Bevacizumab/efectos adversos , Biosimilares Farmacéuticos/efectos adversos , Carboplatino/uso terapéutico , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Método Doble Ciego , Neoplasias Pulmonares/tratamiento farmacológico , Paclitaxel/uso terapéuticoRESUMEN
Tendon is a bundle of tissue comprising of a large number of collagen fibers that connects muscle to bone. However, overuse or trauma may cause degeneration and rupture of the tendon tissues, which imposes an enormous health burden on patients. In addition to autogenous and allogeneic transplantation, which is commonly used in the clinic, the current research on tendon repair is focused on developing an appropriate scaffold via biomaterials and fabrication technology. The development of a scaffold that matches the structure and mechanics of the natural tendon is the key to the success of the repair, so the synergistic optimization of the scaffold fabrication technology and biomaterials has always been a concern of researchers. A series of strategies include the preparation of scaffolds by electrospinning and 3D printing, as well as the application of injectable hydrogels and microspheres, which can be used individually or in combination with cells, growth factors for tendon repair. This review introduces the tendon tissue structure, the repair process, the application of scaffolds, and the current challenges facing biomaterials, and gives an outlook on future research directions. With biomaterials and technology continuing to be developed, we envision that the scaffolds could have an important impact on the application of tendon repair.
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Materiales Biocompatibles , Andamios del Tejido , Humanos , Materiales Biocompatibles/uso terapéutico , Andamios del Tejido/química , Ingeniería de Tejidos , Tendones/cirugía , Tendones/fisiología , Impresión TridimensionalRESUMEN
Massive hemorrhage may be detrimental to the patients, which necessitates the advent of new materials with high hemostatic efficiency and good biocompatibility. The objective of this research was to screen for the effect of the different types of bio-elastomers as hemostatic dressings. 3D loose nanofiber sponges were prepared; PU-TA/Gel showed promising potential. Polyurethane (PU) was synthesized and electrospun to afford porous sponges, which were crosslinked with glutaraldehyde (GA). FTIR and 1H-NMR evidenced the successful synthesis of PU. The prepared PU-TA/Gel sponge had the highest porosity and water absorption ratio. Besides, PU-TA/Gel sponges exhibited cytocompatibility, negligible hemolysis and the shortest clotting time. PU-TA/Gel sponge rapidly induced stable blood clots with shorter hemostasis time and less bleeding volume in a liver injury model in rats. Intriguingly, PU-TA/Gel sponges also induced good skin regeneration in a full-thickness excisional defect model as revealed by the histological analysis. These results showed that the PU-TA/Gel-based sponges may offer an alternative platform for hemostasis and wound healing.
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Tissue engineering (TE) has attracted the widespread attention of the research community as a method of producing patient-specific tissue constructs for the repair and replacement of injured tissues. To date, different types of scaffold materials have been developed for various tissues and organs. The choice of scaffold material should take into consideration whether the mechanical properties, biodegradability, biocompatibility, and bioresorbability meet the physiological properties of the tissues. Owing to their broad range of physico-chemical properties, inorganic materials can induce a series of biological responses as scaffold fillers, which render them a good alternative to scaffold materials for tissue engineering (TE). While it is of worth to further explore mechanistic insight into the use of inorganic nanomaterials for tissue repair, in this review, we mainly focused on the utilization forms and strategies for fabricating electrospun membranes containing inorganic components based on electrospinning technology. A particular emphasis has been placed on the biological advantages of incorporating inorganic materials along with organic materials as scaffold constituents for tissue repair. As well as widely exploited natural and synthetic polymers, inorganic nanomaterials offer an enticing platform to further modulate the properties of composite scaffolds, which may help further broaden the application prospect of scaffolds for TE.
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Osteoarthritis (OA) is one of the most common chronic musculoskeletal diseases, which accounts for a large proportion of physical disabilities worldwide. Herein, we fabricated injectable gelatin/poly(L-lactide)-based nanofibrous microspheres (MS) via electrospraying technology, which were further modified with tannic acid (TA) named as TMS or metal phenolic networks (MPNs) consisting of TA and strontium ions (Sr2+) and named as TSMS to enhance their bioactivity for OA therapy. The TA-modified microspheres exhibited stable porous structure and anti-oxidative activity. Notably, TSMS showed a sustained release of TA as compared to TMS, which exhibited a burst release of TA. While all types of microspheres exhibited good cytocompatibility, TSMS displayed good anti-inflammatory properties with higher cell viability and cartilage-related extracellular matrix (ECM) secretion. The TSMS microspheres also showed less apoptosis of chondrocytes in the hydrogen peroxide (H2O2)-induced inflammatory environment. The TSMS also inhibited the degradation of cartilage along with the considerable repair outcome in the papain-induced OA rabbit model in vivo as well as suppressed the expression level of inflammatory cytokines, such as tumor necrosis factor-alpha (TNF-α) and interleukin-1-beta (IL-1ß). Taken together, TSMS may provide a highly desirable therapeutic option for intra-articular treatment of OA. STATEMENT OF SIGNIFICANCE: Osteoarthritis (OA) is a chronic disease, which is caused by the inflammation of joint. Current treatments for OA achieve pain relief but hardly prevent or slow down the disease progression. Microspheres are at the forefront of drug delivery and tissue engineering applications, which can also be minimal-invasively injected into the joint. Polyphenols and therapeutic ions have been shown to be beneficial for the treatment of diseases related to the joints, including OA. Herein, we prepared gelatin/poly(L-lactide)-based nanofibrous microspheres (MS) via electrospinning incorporated electrospraying technology and functionalized them with the metal phenolic networks (MPNs) consisting of TA and strontium ions (Sr2+), and assessed their potential for OA therapy both in vitro and in vivo.
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Nanofibras , Osteoartritis , Animales , Conejos , Microesferas , Gelatina/farmacología , Peróxido de Hidrógeno/farmacología , Osteoartritis/patología , Condrocitos/metabolismo , Estroncio/farmacologíaRESUMEN
In the last few decades, there has been a progressive increase in the prevalence of allergic rhinitis (AR) in China, where it now affects approximately 250 million people. AR prevention and treatment include allergen avoidance, pharmacotherapy, allergen immunotherapy (AIT), and patient education, among which AIT is the only curative intervention. AIT targets the disease etiology and may potentially modify the immune system as well as induce allergen-specific immune tolerance in patients with AR. In 2017, a team of experts from the Chinese Society of Allergy (CSA) and the Chinese Allergic Rhinitis Collaborative Research Group (C2AR2G) produced the first English version of Chinese AIT guidelines for AR. Since then, there has been considerable progress in basic research of and clinical practice for AIT, especially regarding the role of follicular regulatory T (TFR) cells in the pathogenesis of AR and the use of allergen-specific immunoglobulin E (sIgE) in nasal secretions for the diagnosis of AR. Additionally, potential biomarkers, including TFR cells, sIgG4, and sIgE, have been used to monitor the incidence and progression of AR. Moreover, there has been a novel understanding of AIT during the coronavirus disease 2019 pandemic. Hence, there was an urgent need to update the AIT guideline for AR by a team of experts from CSA and C2AR2G. This document aims to serve as professional reference material on AIT for AR treatment in China, thus improving the development of AIT across the world.
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Cardiovascular disease has become the leading cause of death. A vascular stent is an effective means for the treatment of cardiovascular diseases. In recent years, biodegradable polymeric vascular stents have been widely investigated by researchers because of its degradability and clinical application potential for cardiovascular disease treatment. Compared to non-biodegradable stents, these stents are designed to degrade after vascular healing, leaving regenerated healthy arteries. This article reviews and summarizes the recent advanced methods for fabricating biodegradable polymeric stents, including injection molding, weaving, 3D printing, and laser cutting. Besides, the functional modification of biodegradable polymeric stents is also introduced, including visualization, anti-thrombus, endothelialization, and anti-inflammation. In the end, the challenges and future perspectives of biodegradable polymeric stents were discussed.
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Enfermedades Cardiovasculares , Enfermedad de la Arteria Coronaria , Implantes Absorbibles , Enfermedades Cardiovasculares/terapia , Enfermedad de la Arteria Coronaria/terapia , Humanos , Polímeros , StentsRESUMEN
BACKGROUND: Tyrosine kinase inhibitors (TKI) have been the standard first-line therapy for advanced non-small cell lung cancer (NSCLC) of epidermal growth factor receptor (EGFR) sensitive mutations. Uncommon EGFR mutations are increasingly reported with the development of next-generation sequencing. However, their sensitivity to TKIs is variable with limited clinical evidence. CASE SUMMARY: Here, we report a patient with the rare delE709_T710insD mutation, who showed the favorable efficacy of dacomitinib and achieved a partial response with a progression-free survival of 7.0 mo. CONCLUSION: To our knowledge, this is the first report displaying the clinical efficacy of dacomitinib for patients with delE709_T710insD, which may help to provide alternatives in non-classical variant NSCLC patients. Further studies are warranted to make the optimal choice of EGFR-TKI for rare mutations.
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BACKGROUND: Primary pulmonary enteric adenocarcinoma (PEAC) is a very rare subtype of invasive adenocarcinoma, and there have been no large studies on PEAC to date. Therefore, it is necessary to obtain much more information about the clinical and pathological features, diagnosis, differential diagnosis, and treatment of PEAC. CASE SUMMARY: All clinical data of six patients with confirmed PEAC from 2013 to 2018 were collected, and data on diagnosis, differential diagnosis, and treatment of PEAC are discussed combined with all the associated literature. The mean age of six patients was 64.0 ± 5.6 (59-73) years old. Their clinical manifestations were heterogeneous, and during their disease course, there were no gastrointestinal symptoms. There was no evidence from colonoscopy or imaging studies to suggest digestive tract tumors or new metastases. The most commonly mutated gene was KRAS (50.0%), and the pathological features of the six cases were similar to those of colorectal cancer. CDX2 (83.3%) and CK7 (66.7%) had the highest positive rates upon immunohistochemical examination. In the associated literature, 252 cases were identified, and the most commonly mutated gene was KRAS (42.9%). Additionally, CDX2 (68.3%) and CK7 (85.8%) had the highest positive rates. Patients mainly received surgery, chemotherapy, and radiotherapy, immunotherapy was not included. CONCLUSION: Positive results for CDX2 and CK7 play an important role in the diagnosis and differential diagnosis of PEAC, and immunotherapy or targeted therapy focused on KRAS needs to be further studied for the treatment of PEAC.
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BACKGROUND: Alectinib and crizotinib have been approved as first-line therapies for advanced non-small cell lung cancer (NSCLC) with anaplastic lymphoma kinase (ALK) gene fusion. However, the therapeutic efficacy and side effects are still largely unknown of patients who switched to next-generation ALK tyrosine kinase inhibitors (ALK-TKIs), such as alectinib, after experiencing no disease progression with initial crizotinib treatment. METHODS: This prospective real-world study enrolled patients who were treated with alectinib after experiencing no disease progression with initial crizotinib treatment. The patients' baseline characteristics, objective response rate (ORR) of crizotinib and alectinib, size change of target tumor lesions, treatment regimen and adverse events (AEs) were collected and analyzed. RESULTS: The study included 53 patients, the majority of whom (96.2%) had non-squamous NSCLC. The median age was 51 (range, 31-80) years old. The ORR of first-line crizotinib was 54.7%. The ORR of sequential alectinib was 73.6%, and 90.5% of patients showed further tumor shrinkage after the alectinib treatment. The median progression-free survival was not reached, and 90.5% of patients were still enrolled in the study at the last follow-up. Among them, 34.0% of patients switched to alectinib treatment due to the toxicity. Crizotinib was associated with a higher frequency of AEs of grades 3 and 4 than alectinib (15.1% vs. 0%). Neither group had any AEs resulting in death. CONCLUSIONS: Switching to alectinib might be an option for patients who do not experience disease progression with initial crizotinib therapy, and may promote better treatment compliance.
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The peritrophic matrix (PM) secreted by the midgut cells of insects is formed by the binding of PM proteins to chitin fibrils. The PM envelops the food bolus, serving as a barrier between the content of the midgut lumen and its epithelium, and plays a protective role for epithelial cells against mechanical damage, pathogens, toxins, and other harmful substances. However, few studies have investigated the characteristics and synthesis factors of the PM in the silkworm, Bombyx mori. Here, we examined the characteristics of the PM in the silkworms. The PM thickness of the silkworms increased gradually during growth, while there was no significant difference in thickness along the entire PM region. Permeability of the PM decreased gradually from the anterior to posterior PM. We also found that PM synthesis was affected by food ingestion and the gut microbiota. Our results are beneficial for future studies regarding the function of the PM in silkworms.
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Developing an excellent hemostatic material with good biocompatibility and high blood absorption capacity for rapid hemostasis of deep non-compressible hemorrhage remains a significant challenge. Herein, a novel conjugate electrospinning strategy to prepare an ultralight 3D gelatin sponge consisting of continuous interconnected nanofibers. This unique fluffy nanofiber structure endows the sponge with low density, high surface area, compressibility, and ultrastrong liquid absorption capacity. In vitro assessments show the gelatin nanofiber sponge has good cytocompatibility, high cell permeability, and low hemolysis ratio. The rat subcutaneous implantation studies demonstrate good biocompatibility and biodegradability of gelatin nanofiber sponge. Gelatin nanofiber sponge aggregates and activates platelets in large quantities to accelerate the formation of platelet embolism, and simultaneously escalates other extrinsic and intrinsic coagulation pathways, which collectively contribute to its superior hemostatic capacity. In vivo studies on an ear artery injury model and a liver trauma model of rabbits demonstrate that the gelatin nanofiber sponge rapidly induce stable blood clots with least blood loss compared to gelatin nanofiber membrane, medical gauze, and commercial gelatin hemostatic sponge. Hence, the gelatin nanofiber sponge holds great potential as an absorbable hemostatic agent for rapid hemostasis.
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Hemostáticos , Nanofibras , Animales , Vendajes , Gelatina/farmacología , Hemostasis , Hemostáticos/farmacología , Conejos , RatasRESUMEN
BACKGROUND: Rearrangements of the anaplastic lymphoma kinase (ALK) gene (ALK-positive) represent an oncogenic driver in approximately 3%-5% of non-small-lung cancer (NSCLC) patients. Sarcoidosis is a multisystem disease, and its reported incidence in Asia is 1 or less per 100000 people per year. The co-occurrence of sarcoidosis and ALK-positive NSCLC is rare, and ALK-positive lung cancer is likely to spread quickly. Therefore, the co-occurrence of sarcoidosis is more easily misdiagnosed as metastatic lung cancer by radiological examination. CASE SUMMARY: A 50-year-old man had a nodule in the left superior lobe, many small nodules in left superior and right lungs, and enlarged bilateral hilar, mediastinal, and right supraclavicular lymph nodes. Computed tomography-guided pulmonary biopsy of the nodule in the left superior lobe revealed echinoderm microtubule-associated protein-like 4 gene-ALK positive NSCLC with concomitant noncaseating granuloma. This patient was treated with crizotinib. Thirty days later, a chest computed tomography scan revealed a dramatic decrease in the size of the left superior lobe nodule; however, the lesions in the right lung progressed. The right supraclavicular lymph nodes showed granulomas, and no tumor cells were identified in the specimens. The angiotensin-converting enzyme level was high. After 1 wk of methylprednisolone treatment, a significant response of all lesions was revealed. Following radical resection of the lung cancer, noncaseating granulomas were observed in both lung tissues and lymph nodes, which resulted in a diagnosis of echinoderm microtubule-associated protein-like 4-ALK positive NSCLC accompanied with sarcoidosis. CONCLUSION: Our experience illustrates that pathological evidence is needed to confirm metastatic disease, especially when some suspected metastatic lesions are negative for malignancy.