ABSTRACT
The ammonium ethyl acryloylphosphoramidate (AEA) was synthesized by acrylamide, ethanolamine, and phosphorus oxychloride; the nuclear magnetic resonance (NMR) and Fourier transform infrared spectroscopy (FTIR) were applied to analyze the structure of AEA molecule. Using the dip-cure process to treat raw cotton (RC) with AEA flame retardant, the finished fabric had excellent flame retardancy. The cone calorimeter, thermogravimetric, FTIR, and vertical flame tests illustrated finished fabrics underwent synergistic and condensed-phase flame retardation. The finished fabric also had excellent durability, and the higher the sealing degree of phosphorus atoms, the higher the durability. The limiting oxygen index (LOI) of RC-AEA3-20 (raw cotton finished with 20â¯wt% AEA3) reached 45.4â¯%. However, the LOI only dropped to 34.9â¯% after 50 laundering cycles under the AATCC 61-2013 3 A standard. The excellent durability and FTIR analyses of finished fabrics suggested that the -N-P(=O)-O-C- covalent bond was formed between flame retardant and cellulose. This covalent bond exhibited a p-π conjugation effect, enhancing the stability of -N-P(=O)-O-C- bond, improving the durability of finished fabrics. In conclusion, adding reactive groups into flame retardants, like CH2=CH- and -N-P(=O)-O-NH4+, could increase the durability of finished cotton fabrics.
ABSTRACT
AIMS: MicroRNA-126 (miR-126), one of the most abundant microRNAs in platelets, is involved in the regulation of platelet activity and the circulating miR-126 is reduced during antiplatelet therapy. However, whether intraplatelet miR-126 plays a role in thrombosis and platelet inhibition remains unclear. METHODS AND RESULTS: Here, using tissue-specific knockout mice, we reported that the deficiency of miR-126 in platelets and vascular endothelial cells significantly prevented thrombosis and prolonged bleeding time. Using chimeric mice, we identified that the lack of intraplatelet miR-126 significantly prevented thrombosis. Ex vivo experiments further demonstrated that miR-126-deficient platelets displayed impaired platelet aggregation, spreading and secretory functions. Next, miR-126 was confirmed to target phosphoinositol-3 kinase regulatory subunit 2 (PIK3R2) in platelet, which encodes a negative regulator of the PI3 K/AKT pathway, enhancing platelet activation through activating the integrin αIIbß3-mediated outside-in signaling. After undergoing myocardial infarction (MI), chimeric mice lacking intraplatelet miR-126 displayed reduced microvascular obstruction and prevented MI expansion in vivo. In contrast, overexpression of miR-126 by the administration of miR-126 agonist (agomiR-126) in wild-type mice aggravated microvascular obstruction and promoted MI expansion, which can be almost abolished by aspirin administration. In patients with cardiovascular diseases, antiplatelet therapies, either aspirin alone or combined with clopidogrel, decreased the level of intraplatelet miR-126. The reduction of intraplatelet miR-126 level was associated with the decrease of platelet activity. CONCLUSIONS: Our murine and human data reveal that (i) intraplatelet miR-126 contributes to platelet activity and promotes thrombus formation, and (ii) the reduction of intraplatelet miR-126 contributes to platelet inhibition during antiplatelet therapy.
ABSTRACT
The phosphoramide phosphorus ester phosphate ammonium (PPEPA) flame retardant was synthesized by phosphorus oxychloride and ethanolamine, and its structure was characterized by nuclear magnetic resonance and Fourier transform infrared spectroscopy (FTIR). Cotton textiles treated with 20 wt% PPEPA (CT-PPEPA3) would have high durability and flame retardance. The limiting oxygen index (LOI) of CT-PPEPA3 was found to be 46.5 %, while after undergoing 50 laundering cycles (LCs) following the AATCC 61-2013 3 A standard, the LOI only decreased to 31.4 %. Scanning electron microscopy and X-ray diffraction analyses suggested the penetration of PPEPA molecules into the interior of cotton fibers, resulting in a minor alteration of the cellulose crystal structure. The excellent durability, FTIR, and energy-dispersive X-ray of CT-PPEPA3 provided evidence for the formation of -N-P(=O)-O-C- and -O-P(=O)-O-C- covalent bonds between the PPEPA molecules and cellulose. The -N-P(=O)-O-C- bond exhibited a p-π conjugation effect, leading to enhanced stability and improved durability of the flame-retardant cotton textiles. Vertical flame, thermogravimetric, and cone calorimetry tests demonstrated that the CT-PPEPA3 underwent condensed-phase and synergistic flame retardation. Additionally, these finished cotton textiles retained adequate breaking strength and softness, making them suitable for various applications. In conclusion, the incorporation of the -N-P(=O)-ONH4 group into the phosphorus ester phosphate ammonium flame retardant demonstrated effective enhancement of the fire resistance and durability of treated cotton textiles.
Subject(s)
Ammonium Compounds , Flame Retardants , Phosphorus , Phosphates , Phosphoramides , Textiles , Cotton Fiber , CelluloseABSTRACT
In our efforts to develop inhibitors selective for neuronal nitric oxide synthase (nNOS) over endothelial nitric oxide synthase (eNOS), we found that nNOS can undergo conformational changes in response to inhibitor binding that does not readily occur in eNOS. One change involves movement of a conserved tyrosine, which hydrogen bonds to one of the heme propionates, but in the presence of an inhibitor, changes conformation, enabling part of the inhibitor to hydrogen bond with the heme propionate. This movement does not occur as readily in eNOS and may account for the reason why these inhibitors bind more tightly to nNOS. A second structural change occurs upon the binding of a second inhibitor molecule to nNOS, displacing the pterin cofactor. Binding of this second site inhibitor requires structural changes at the dimer interface, which also occurs more readily in nNOS than in eNOS. Here, we used a combination of crystallography, mutagenesis, and computational methods to better understand the structural basis for these differences in NOS inhibitor binding. Computational results show that a conserved tyrosine near the primary inhibitor binding site is anchored more tightly in eNOS than in nNOS, allowing for less flexibility of this residue. We also find that the inefficiency of eNOS to bind a second inhibitor molecule is likely due to the tighter dimer interface in eNOS compared with nNOS. This study provides a better understanding of how subtle structural differences in NOS isoforms can result in substantial dynamic differences that can be exploited in the development of isoform-selective inhibitors.
Subject(s)
Nitric Oxide Synthase Type III , Nitric Oxide Synthase , Nitric Oxide Synthase/metabolism , Nitric Oxide Synthase Type III/genetics , Nitric Oxide Synthase Type III/chemistry , Nitric Oxide Synthase Type I , Protein Isoforms/chemistry , Crystallography, X-Ray , Enzyme Inhibitors/pharmacology , Heme/chemistry , Tyrosine , Nitric OxideABSTRACT
BACKGROUND: The repair and reconstruction of medial meniscus posterior root tears (MMPRTs) is an important issue in the field of orthopedic sports medicine. This study reports the first application of arthroscopic linear chain fixation for the treatment of MMPRTs. CASE PRESENTATION: A 78-year-old female patient presented with a 1.5-month history of right knee pain accompanied by a locked facet joint. The patient underwent surgery with the new linear chain fixation method. In this method, the suture and the loop part of the buckle-strap titanium plate were combined into a linear chain mechanical complex, and the tension of the posterior root stump was gradually increased by pulling on the two attachment lines at the external mouth of the tibial tunnel. The postoperative Lysholm score was 89, and the visual analogue scale score was 0.9, indicating a significant improvement in knee joint function. At the 7-month and 1-year post-surgery follow-up, physical and MRI examinations confirmed satisfactory healing of the MMPRTs. CONCLUSION: This surgical approach offers several benefits, including a simplified instrumentation setup, preservation of natural anatomical structures, and reliable residual stump fixation. It has the potential for clinical implementation.
Subject(s)
Menisci, Tibial , Tibial Meniscus Injuries , Female , Humans , Aged , Menisci, Tibial/diagnostic imaging , Menisci, Tibial/surgery , Arthroscopy/methods , Tibial Meniscus Injuries/diagnostic imaging , Tibial Meniscus Injuries/surgery , Knee Joint/surgery , Tibia , RuptureABSTRACT
Both ursolic acid (UA) and sorafenib (Sora) have been generally utilized in cancer treatment, and the combination of the two has also shown a good anti-tumor effect. However, single-agent therapy for Hepatocellular carcinoma (HCC) has the disadvantages of multi-drug resistance, poor water solubility and low bioavailability, and the application of traditional nanocarrier materials is limited due to their low drug loading and low carrier-related toxicity. Therefore, we prepared US NPs with different proportions of UA and Sora by solvent exchange method for achieving synergistic HCC therapy. US NPs had suitable particle size, good dispersibility and storage stability, which synergistically inhibited the proliferation of HepG2 cells, SMMC7721 cells and H22 cells. In addition, we also proved that US NPs were able to suppress the migration of HepG2 cells and SMMC7721 cells and reduce the adhesion ability and colony formation ability of these cells. According to the results, US NPs could degrade the membrane potential of mitochondrial, participate in cell apoptosis, and synergistically induce autophagy. Collectively, the carrier-free US NPs provide new strategies for HCC treatment and new ideas for the development of novel nano-drug delivery systems containing UA and Sora.
Subject(s)
Antineoplastic Agents , Carcinoma, Hepatocellular , Liver Neoplasms , Nanoparticles , Humans , Sorafenib/pharmacology , Sorafenib/therapeutic use , Carcinoma, Hepatocellular/pathology , Ursolic Acid , Pharmaceutical Preparations , Liver Neoplasms/pathology , Cell Line, TumorABSTRACT
OBJECTIVE: To differentiate between atypical cartilaginous tumors and high-grade chondrosarcoma of the major long bones using intravoxel incoherent motion (IVIM) and Dynamic Contrast-Enhanced magnetic resonance imaging (DCE-MRI), and explore the correlation of quantitative parameters with hypoxia inducible factor-1α (HIF-1α), vascular endothelial growth factor (VEGF) and microvessel density (MVD). METHOD: Between September 2016 and March 2022, 35 patients (17 atypical cartilaginous tumors, 18 high-grade chondrosarcoma) underwent MRI examination and pathological confirmation at our hospital. First, IVIM-derived parameters ( D , D* , and f ), and DCE-MRI parameters ( Ktrans , Kep , and V e ) were measured, and intraclass correlation efficient (ICC) and Mann-Whitney U test were performed. Second, receiver-operating characteristic curve analysis was performed to evaluate the diagnostic performance. Finally, Spearman's correlation analysis was performed between the quantitative parameters of IVIM-DWI and DCE-MRI and the immunohistochemical factors HIF-1α, VEGF, and MVD in chondrosarcoma tissue. RESULTS: D in atypical cartilaginous tumors was significantly higher than that in high-grade chondrosarcoma ( P = 0.003), whereas D* , Ktrans , and K ep in atypical cartilaginous tumors were significantly lower than those in high-grade chondrosarcoma (all P < 0.001). Ktrans demonstrated the highest area under the curve (AUC) of 0.979. The D* , Ktrans , and K ep were positively correlated with HIF-1α, VEGF, and MVD (all P < 0.001), whereas D had no correlation with HIF-1α, VEGF, and MVD ( P = 0.113, 0.077, 0.058, respectively). CONCLUSION: The IVIM-DWI quantitative parameters ( D , D* ) and DCE-MRI quantitative parameters ( Ktrans , Kep ) are helpful to differentiate between atypical cartilaginous tumors and high-grade chondrosarcoma and could be imaging biomarkers to reflect the expressions of HIF-1α, VEGF, and angiogenesis of chondrosarcoma.
Subject(s)
Bone Neoplasms , Chondrosarcoma , Humans , Vascular Endothelial Growth Factor A , Contrast Media , Magnetic Resonance Imaging/methods , Chondrosarcoma/diagnostic imaging , Motion , Bone Neoplasms/diagnostic imaging , Diffusion Magnetic Resonance Imaging/methodsABSTRACT
The effectiveness of chemotherapeutic agents for hepatocellular carcinoma (HCC) is unsatisfactory because of tumor heterogeneity, multidrug resistance, and poor target accumulation. Therefore, multimodality-treatment with accurate drug delivery has become increasingly popular. Herein, a cell penetrating peptide-aptamer dual modified-nanocomposite (USILA NPs) was successfully constructed by coating a cell penetrating peptide and aptamer onto the surface of sorafenib (Sora), ursolic acid (UA) and indocyanine green (ICG) condensed nanodrug (USI NPs) via one-pot assembly for targeted and synergistic HCC treatment. USILA NPs showed higher cellular uptake and cytotoxicity in HepG2 and H22 cells, with a high expression of epithelial cell adhesion molecule (EpCAM). Furthermore, these NPs caused more significant mitochondrial membrane potential reduction and cell apoptosis. These NPs could selectively accumulate at the tumor site of H22 tumor-bearing mice and were detected with the help of ICG fluorescence; moreover, they retarded tumor growth better than monotherapy. Thus, USILA NPs can realize the targeted delivery of dual drugs and the integration of diagnosis and treatment. Moreover, the effects were more significant after co-administration of iRGD peptide, a tumor-penetrating peptide with better penetration promoting ability or programmed cell death ligand 1 (PD-L1) antibody for the reversal of the immunosuppressive state in the tumor microenvironment. The tumor inhibition rates of USILA NPs + iRGD peptide or USILA NPs + PD-L1 antibody with good therapeutic safety were 72.38 % and 67.91 % compared with control, respectively. Overall, this composite nanosystem could act as a promising targeted tool and provide an effective intervention strategy for enhanced HCC synergistic treatment.
Subject(s)
Carcinoma, Hepatocellular , Cell-Penetrating Peptides , Liver Neoplasms , Nanoparticles , Mice , Animals , Carcinoma, Hepatocellular/drug therapy , Carcinoma, Hepatocellular/pathology , Pharmaceutical Preparations , Liver Neoplasms/drug therapy , Liver Neoplasms/pathology , Cell-Penetrating Peptides/chemistry , B7-H1 Antigen/therapeutic use , Nanoparticles/chemistry , Cell Line, Tumor , Tumor MicroenvironmentABSTRACT
Starting from the perspective of meridian theory, this article briefly analyzes the meridian pathophysiology of snoring and the relationship between snoring and meridian theory. It proposes that acupuncture treatment for snoring should focus on regulating qi from the shaoyang meridians, harmonizing the spirit by the governor vessel, resolving phlegm through the three yang meridians, and harmonizing qi and blood from the yangming meridians. Additionally, attention is placed on both the root cause and the symptoms, the theory of "four seas". The ultimate goal is to promote the flow of meridian and qi-blood, improve symptoms such as nighttime snoring, poor sleep quality, and daytime sleepiness, and achieve the desired outcome of stopping snoring and ensuring restful sleep.
Subject(s)
Acupuncture Therapy , Meridians , Sleep Initiation and Maintenance Disorders , Humans , Snoring/therapy , Mucus , Acupuncture PointsABSTRACT
BACKGROUND: Asparaginase (ASP) is an important drug in combined chemotherapy regimens for pediatric acute lymphoblastic leukemia (ALL); ASP-associated pancreatitis (AAP) is the main adverse reaction of ASP. Recurrent pancreatitis is a complication of AAP, for which medication is ineffective. AIM: To evaluate the efficacy and safety of endoscopic retrograde cholangiopancreatography (ERCP) in treating recurrent pancreatitis due to AAP. METHODS: From May 2018 to August 2021, ten children (five males and five females; age range: 4-13 years) with AAP were treated using ERCP due to recurrent pancreatitis. Clinical data of the ten children were collected, including their sex, age, weight, ALL risk grading, clinical symptoms at the onset of pancreatitis, time from the first pancreatitis onset to ERCP, ERCP operation status, and postoperative complications. The symptomatic relief, weight change, and number of pancreatitis onsets before and after ERCP were compared. RESULTS: The preoperative symptoms were abdominal pain, vomiting, inability to eat, weight loss of 2-7 kg, and 2-9 pancreatitis onsets. After the operation, nine of ten patients did not develop pancreatitis, had no abdominal pain, could eat normally; the remaining patient developed three pancreatitis onsets due to the continuous administration of ASP, but eating was not affected. The postoperative weight gain was 1.5-8 kg. There was one case of post ERCP pancreatitis and two cases of postoperative infections; all recovered after medication. CONCLUSION: ERCP improved clinical symptoms and reduced the incidence of pancreatitis, and was shown to be a safe and effective method for improving the management of recurrent pancreatitis due to AAP.
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Abnormal proliferation of pulmonary arterial smooth muscle cells (PASMCs) is a key mechanism in the development of pulmonary arterial hypertension (PAH). Signal transducer and activator of transcription 3 (STAT3) signalling plays a critical role in modulating PASMC proliferation, and G-protein-coupled receptor kinase 6 (GRK6) regulates the STAT3 pathway. However, the mechanism underlying the relationship between GRK6 and PAH remains unclear. In this study, we aimed to investigate the role of GRK6 in PAH and determine its potential as a therapeutic target. We utilised hypoxia- and SU5416-induced PAH mouse models and a monocrotaline-induced PAH rat model to analyse the involvement of GRK6. We conducted gain- and loss-of-function experiments using mouse PASMCs. Modulation of GRK6 expression was achieved via a lentiviral vector in vitro and an adeno-associated virus serotype 1 encoding GRK6 in vivo. GRK6 was significantly downregulated in the lung tissues of PAH mice and rats, predominantly in PASMCs. Knockout of GRK6 exacerbated PAH, while both therapeutic and prophylactic overexpression of GRK6 alleviated PAH, as evidenced by a reduction in right ventricular systolic pressure, right ventricular wall to left ventricular wall plus ventricular septum ratio, pulmonary vascular media thickness, and pulmonary vascular muscularisation. Mechanistically, GRK6 overexpression attenuated hypoxia-induced PASMC proliferation and STAT3 phosphorylation. Conversely, knockdown of GRK6 promoted hypoxia-induced proliferation, which was mitigated by a STAT3 inhibitor. Our findings highlight the potential protective and beneficial roles of GRK6 in PAH; we propose a lung-targeted GRK6 gene therapy utilizing adeno-associated virus serotype 1 as a potential treatment approach for patients with PAH.
Subject(s)
Hypertension, Pulmonary , Pulmonary Arterial Hypertension , Humans , Rats , Mice , Animals , Hypertension, Pulmonary/genetics , Hypertension, Pulmonary/prevention & control , Hypertension, Pulmonary/drug therapy , Rats, Sprague-Dawley , Cell Proliferation , Mice, Knockout , Pulmonary Artery , Hypoxia/metabolism , Myocytes, Smooth Muscle/metabolism , Cells, CulturedABSTRACT
Bisphenol S (BPS), being structurally similar to bisphenol A (BPA), has been widely used as an alternative to BPA in industrial applications. However, in-depth studies on the environmental behavior and fate of BPS in various soils have been rarely reported. Here, 14C-labeled BPS was used to investigate its mineralization, bound residues (BRs) formation and extractable residues (ERs) in three soils for 64 days. Significant differences were found in the dissipation rates of BPS in three soils with different pH values. The dissipation of BPS followed pseudo first-order kinetics with half-lives (T1/2) of 15.2 ± 0.1 d, 27.0 ± 0.2 d, 180.4 ± 5.3 d, and 280.5 ± 3.3 d in the alkaline soil (fluvo-aquic soil, FS), the neutral soil (cinnamon soil, CS), the acidic soil (red soil, RS), and sterilized cinnamon soil (CS-S), respectively. The mineralization and BRs formation contributed the most to the dissipation of BPS in soil. BPS was persistent in acidic soil, and may pose a significant threat to plants grown in acidic soils. Additionally, soil microorganisms played a key role in BPS degradation, and the organic matter content might be a major factor that promotes the adsorption and degradation of BPS in soils. Two transformed products, P-hydroxybenzenesulfonic acid and methylated BPS were identified in soils. This study provides new insights into the fate of BPS in various soils, which will be useful for risk assessments of BPS in soil.
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CRISPR/Cas9 genome editing is a promising therapeutic technique, which makes precise and rapid gene editing technology possible on account of its high sensitivity and efficiency. CRISPR/Cas9 system has been proved to able to effectively disrupt and modify genes, which shows great potential for cancer treatment. Current researches proves that virus vectors are capable of effectively delivering the CRISPR/Cas9 system, but immunogenicity and carcinogenicity caused by virus transmission still trigger serious consequences. Therefore, the greatest challenge of CRISPR/Cas9 for cancer therapy lies on how to deliver it to the target tumor site safely and effectively. Non-viral delivery systems with specific targeting, high loading capacity, and low immune toxicity are more suitable than viral vectors, which limited by uncontrollable side effects. Their medical advances and applications have been widely concerned. Herein, we present the molecule mechanism and different construction strategies of CRISPR/Cas9 system for editing genes at the beginning of this research. Subsequently, several common CRISPR/Cas9 non-viral deliveries for cancer treatment are introduced. Lastly, based on the main factors limiting the delivery efficiency of non-viral vectors proposed in the existing researches and literature, we summarize and discuss the main methods to solve these limitations in the existing tumor treatment system, aiming to introduce further optimization and innovation of the CRISPR/Cas9 non-viral delivery system suitable for cancer treatment.
Subject(s)
CRISPR-Cas Systems , Neoplasms , Gene Editing , Technology , Neoplasms/genetics , Neoplasms/therapyABSTRACT
BACKGROUND AND AIMS: Arterial calcification is the predictor of cardiovascular risk in diabetic patients. Nε-carboxymethyl-lysine (CML), a toxic metabolite, is associated with accelerated vascular calcification in diabetes mellitus (DM). However, the mechanism remains elusive. This study aims to explore the key regulators involved in CML-induced vascular calcification in DM. METHODS: We used Western blot and immuno-staining to test the expression and localization of nuclear factor of activated T cells, cytoplasmic 1 (NFATc1) in human samples, a diabetic apolipoprotein E-deficient (ApoE-/-) mouse model, and a vascular smooth muscle cells (VSMC) model. Further, we confirmed the regulator of NFATc1 phosphorylation and acetylation induced by CML. The role of NFATc1 in VSMCs calcification and osteogenic differentiation was explored in vivo and in vitro. RESULTS: In diabetic patients, CML and NFATc1 levels increased in the severe calcified anterior tibial arteries. CML significantly promoted NFATc1 expression and nuclear translocation in VSMCs and mouse aorta. Knockdown of NFATc1 significantly inhibited CML-induced calcification. CML promoted NFATc1 acetylation at K549 by downregulating sirtuin 3 (SIRT3), which antagonized the focal adhesion kinase (FAK) induced NFATc1 phosphorylation at the Y270 site. FAK and SIRT3 affected the nuclear translocation of NFATc1 by regulating the acetylation-phosphorylation crosstalk. NFATc1 dephosphorylation mutant Y270F and deacetylation mutant K549R had opposite effects on VSMC calcification. SIRT3 overexpression and FAK inhibitor could reverse CML-promoted VSMC calcification. CONCLUSIONS: CML enhances vascular calcification in DM through NFATc1. In this process, CML increases NFATc1 acetylation by downregulating SIRT3 to antagonize FAK-induced NFATc1 phosphorylation.
Subject(s)
Diabetes Mellitus , Sirtuin 3 , Vascular Calcification , Animals , Humans , Mice , Acetylation , Cells, Cultured , Focal Adhesion Protein-Tyrosine Kinases/metabolism , Myocytes, Smooth Muscle/metabolism , NFI Transcription Factors/metabolism , NFI Transcription Factors/pharmacology , Osteogenesis , Phosphorylation , Vascular Calcification/genetics , Vascular Calcification/metabolismABSTRACT
Thrombus is one of the culprits for global health problems. However, most current antithrombotic drugs are limited by restricted targeting ability and a high risk of systemic bleeding. A hybrid cell membrane-coated biomimetic nanosystem (PM/RM@PLGA@P/R) was constructed in this paper to fulfil the targeted delivery of ginsenoside (Rg1) and perfluorohexane (PFH). Poly lactic-co-glycolic acid (PLGA) is used as carriers to coat Rg1 and PFH. Thanks to the camouflage of erythrocyte membrane (RM) and platelet membrane (PM), the nanosystem in question possesses remarkable features including immune escape and self-targeting. Therefore, a compact nano-core with PLGA@P/R was formed, with a hybrid membrane covering the surface of the core, forming a "core-shell" structure. With its "core-shell" structure, this nanoparticle fancifully combines the advantages of both PFH (the low-intensity focused ultrasound (LIFU)-responsive phase-change thrombolysis) and Rg1(the antioxidant, anti-inflammatory and anticoagulant abilities). Meanwhile, PM/RM@PLGA@P/R nanoparticles exhibits superior in-vitro performance in terms of ROS scavenging, anticoagulant activity and immune escape compared with those without cell membranes (PLGA@P/R). Furthermore, in the animal experiment in which the tail vein thrombosis model was established by injecting k-carrageenan, the combined treatment of LIFU and PM/RM@PLGA@P/R showed a satisfactory antithrombotic efficiency (88.20 %) and a relatively higher biological safety level. This strategy provides new insights into the development of more effective and safer targeted biomimetic nanomedicines for antithrombotic treatments, possessing potential application in synergistic therapy field.
Subject(s)
Ginsenosides , Nanoparticles , Thrombosis , Animals , Fibrinolytic Agents/pharmacology , Fibrinolytic Agents/chemistry , Erythrocyte Membrane , Ginsenosides/pharmacology , Biomimetics , Thrombosis/drug therapy , Anticoagulants , Nanoparticles/chemistryABSTRACT
OBJECTIVE: Some studies have reported that the prognosis of total laparoscopic hysterectomy (TLH) for early-stage cervical cancer (CC) is worse than that of open surgery. And this was associated with the use of uterine manipulator or not. Therefore, this study retrospectively analyzes the efficacy and safety of TLH without uterine manipulator combined with pelvic lymphadenectomy for early-stage CC. METHODS: Fifty-eight patients with CC (stage IB1-IIA1) who received radical hysterectomy from September 2019 to January 2020 were divided into no uterine manipulator (n = 26) and uterine manipulator group (n = 32). Then, clinical characteristics were collected and intraoperative/postoperative related indicators were compared. RESULTS: Patients in the no uterine manipulator group had significantly higher operation time and blood loss than in the uterine manipulator group. Notably, there was no significant difference in hemoglobin change, blood transfusion rate, number of pelvic nodules, anal exhaust time, complications and recurrence rate between the two groups. Additionally, patients in the uterine manipulator group were prone to urinary retention (15.6%) and lymphocyst (12.5%), while the no uterine manipulator group exhibited high probability of bladder dysfunction (23.1%) and urinary retention (15.4%). Furthermore, the 1-year disease-free survival rate and the 1-year overall survival rate were not significantly different between the two groups. CONCLUSION: There was no significant difference in the efficacy and safety of TLH with or without uterine manipulator combined with pelvic lymphadenectomy in the treatment of patients with early-stage CC. However, the latter requires consideration of the negative effects of high operation time and blood loss.
Subject(s)
Hysterectomy , Laparoscopy , Urinary Retention , Uterine Cervical Neoplasms , Female , Humans , Hysterectomy/adverse effects , Laparoscopy/adverse effects , Lymph Node Excision/adverse effects , Neoplasm Staging , Retrospective Studies , Uterine Cervical Neoplasms/pathology , Uterine Cervical Neoplasms/surgeryABSTRACT
The composition of influenza vaccines is updated annually. To ensure vaccine safety, the coverage and adverse events following immunization (AEFI) of 6 manufacturers of trivalent inactivated influenza vaccine (TIV3) need to be evaluated. In January 2022, we analyzed data from more than 1.59 million children in the Childhood Vaccination Information Management System and the AEFI Surveillance Information Management System and evaluated influenza vaccines for children aged 6 to 35 months in Guangzhou from 2016/17 to 2019/20 Vaccination rates and AEFI reporting rates. From 2016/17 to 2019/20, the 1-dose influenza vaccination rate was 25.0% (range: 20.7%-30.2%), and the 2-dose (full course) influenza vaccination rate was 21.6% (range: 17.7%-26.4%). The full vaccination coverage rate has trended down since 2017/2018 (2017/18: 26.0%; 2018/19: 8.3; 2019/20: 17.7%). Fifty-two cases (13.1/100 000) and 24 cases (6.9/100 000) received AEFI reports for 1 dose and 2 doses, respectively, mainly due to fever ≥38.6°C (39 cases for 1 dose, 9.8/100 000; 15 cases for 2 dose, 4.3/100 000) and allergic rash (9 cases with 1 dose, 2.3/100 000; 5 cases with 2 doses, 1.4/100 000). Patients who received A and F manufacturers were more likely to report side effects. The safety of influenza vaccines from 6 manufacturers is good, and it is necessary to improve the recommended information on influenza vaccines to dispel people's concerns and increase the vaccination rate.
Subject(s)
Exanthema , Influenza Vaccines , Influenza, Human , Vaccination Coverage , Vaccines, Inactivated , Child , Humans , Infant , Exanthema/chemically induced , Immunization , Influenza Vaccines/adverse effects , Influenza, Human/prevention & control , Influenza, Human/epidemiology , Vaccination , Vaccines, Inactivated/adverse effectsABSTRACT
BACKGROUND: Acute pancreatitis is the most common complication of endoscopic retrograde cholangiopancreatography (ERCP). Currently, there is no suitable treatment for post-ERCP pancreatitis (PEP) prophylaxis. Few studies have prospectively evaluated interventions to prevent PEP in children. AIM: To assess the efficacy and safety of the external use of mirabilite to prevent PEP in children. METHODS: This multicenter, randomized controlled clinical trial enrolled patients with chronic pancreatitis scheduled for ERCP according to eligibility criteria. Patients were randomly divided into the external use of mirabilite group (external use of mirabilite in a bag on the projected abdominal area within 30 min before ERCP) and blank group. The primary outcome was the incidence of PEP. The secondary outcomes included the severity of PEP, abdominal pain scores, levels of serum inflammatory markers [tumor necrosis factor-alpha (TNF-α) and serum interleukin-10 (IL-10)], and intestinal barrier function markers [diamine oxidase (DAO), D-lactic acid, and endotoxin]. Additionally, the side effects of topical mirabilite were investigated. RESULTS: A total of 234 patients were enrolled, including 117 in the external use of mirabilite group and the other 117 in the blank group. The pre-procedure and procedure-related factors were not significantly different between the two groups. The incidence of PEP in the external use of mirabilite group was significantly lower than that in the blank group (7.7% vs 26.5%, P < 0.001). The severity of PEP decreased in the mirabilite group (P = 0.023). At 24 h after the procedure, the visual analog scale score in the external use of mirabilite group was lower than that in the blank group (P = 0.001). Compared with those in the blank group, the TNF-α expressions were significantly lower and the IL-10 expressions were significantly higher at 24 h after the procedure in the external use of mirabilite group (P = 0.032 and P = 0.011, respectively). There were no significant differences in serum DAO, D-lactic acid, and endotoxin levels before and after ERCP between the two groups. No adverse effects of mirabilite were observed. CONCLUSION: External use of mirabilite reduced the PEP occurrence. It significantly alleviated post-procedural pain and reduced inflammatory response. Our results favor the external use of mirabilite to prevent PEP in children.
ABSTRACT
Regeneration is the regrowth of damaged tissues or organs, a vital process in response to damages from primitive organisms to higher mammals. Planarian possesses active whole-body regenerative capability owing to its vast reservoir of adult stem cells, neoblasts, providing an ideal model to delineate the underlying mechanisms for regeneration. RNA N6 -methyladenosine (m6 A) modification participates in many biological processes, including stem cell self-renewal and differentiation, in particular the regeneration of haematopoietic stem cells and axons. However, how m6 A controls regeneration at the whole-organism level remains largely unknown. Here, we demonstrate that the depletion of m6 A methyltransferase regulatory subunit wtap abolishes planarian regeneration, potentially through regulating genes related to cell-cell communication and cell cycle. Single-cell RNA-seq (scRNA-seq) analysis unveils that the wtap knockdown induces a unique type of neural progenitor-like cells (NP-like cells), characterized by specific expression of the cell-cell communication ligand grn. Intriguingly, the depletion of m6 A-modified transcripts grn, cdk9 or cdk7 partially rescues the defective regeneration of planarian caused by wtap knockdown. Overall, our study reveals an indispensable role of m6 A modification in regulating whole-organism regeneration.
Subject(s)
Adult Stem Cells , Planarians , Animals , Planarians/genetics , Planarians/metabolism , RNA Interference , Cell Differentiation/genetics , Cell Division , MammalsABSTRACT
The transcription factor BTB and CNC homology 1(BACH1) has been linked to coronary artery disease risk by human genome-wide association studies, but little is known about the role of BACH1 in vascular smooth muscle cell (VSMC) phenotype switching and neointima formation following vascular injury. Therefore, this study aims to explore the role of BACH1 in vascular remodeling and its underlying mechanisms. BACH1 was highly expressed in human atherosclerotic plaques and has high transcriptional factor activity in VSMCs of human atherosclerotic arteries. VSMC-specific loss of Bach1 in mice inhibited the transformation of VSMC from contractile to synthetic phenotype and VSMC proliferation and attenuated the neointimal hyperplasia induced by wire injury. Mechanistically, BACH1 suppressed chromatin accessibility at the promoters of VSMC marker genes via recruiting histone methyltransferase G9a and cofactor YAP and maintaining the H3K9me2 state, thereby repressing VSMC marker genes expression in human aortic smooth muscle cells (HASMCs). BACH1-induced repression of VSMC marker genes was abolished by the silencing of G9a or YAP. Thus, these findings demonstrate a crucial regulatory role of BACH1 in VSMC phenotypic transition and vascular homeostasis and shed light on potential future protective vascular disease intervention via manipulation of BACH1.