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To investigate the safety and efficacy of long-acting glucagon like peptide-1 receptor agonists in overweight or obese patients with type 2 diabetes. Overweight or obese patients with type 2 diabetes from July 2021 to June 2022 were randomly divided into control group (metformin) and experimental group (metformin + dulaglitide or semaglutide). Repeated measures analysis of variance was used to compare Hemoglobin A1c, fasting plasma glucose and body mass index (BMI) of patients before treatment, 6 months and 12 months after treatment. The adverse reactions of patients before treatment and 12 months after treatment were analyzed. The time effect of Hemoglobin A1c, fasting plasma glucose and BMI in the control group (nâ =â 35) and the experimental group (nâ =â 32) were statistically significant (Pâ <â .001), and the intergroup effect of BMI was statistically significant (Pâ <â .05). The interaction effect of BMI was statistically significant (Pâ <â .001). The BMI level of the experimental group was lower than that of the control group at 6 and 12 months after treatment (Pâ <â .001). There was no significant difference in the incidence of adverse reactions between the 2 groups (Pâ >â .05). Long-acting glucagon like peptide-1 receptor agonists, such as dulaglitide and semaglutide, not only reduce glycosylated hemoglobin levels, but also significantly improve BMI in overweight or obese patients with type 2 diabetes.
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Glucemia , Índice de Masa Corporal , Diabetes Mellitus Tipo 2 , Receptor del Péptido 1 Similar al Glucagón , Péptidos Similares al Glucagón , Hemoglobina Glucada , Hipoglucemiantes , Metformina , Obesidad , Sobrepeso , Humanos , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/complicaciones , Masculino , Persona de Mediana Edad , Femenino , Receptor del Péptido 1 Similar al Glucagón/agonistas , Hipoglucemiantes/uso terapéutico , Péptidos Similares al Glucagón/uso terapéutico , Péptidos Similares al Glucagón/administración & dosificación , Péptidos Similares al Glucagón/análogos & derivados , Hemoglobina Glucada/efectos de los fármacos , Hemoglobina Glucada/análisis , Obesidad/tratamiento farmacológico , Obesidad/complicaciones , Metformina/uso terapéutico , Sobrepeso/tratamiento farmacológico , Sobrepeso/complicaciones , Glucemia/efectos de los fármacos , Glucemia/análisis , Anciano , Fragmentos Fc de Inmunoglobulinas/uso terapéutico , Fragmentos Fc de Inmunoglobulinas/efectos adversos , Análisis de Varianza , Adulto , Quimioterapia Combinada , Agonistas Receptor de Péptidos Similares al Glucagón , Proteínas Recombinantes de FusiónRESUMEN
Dupilumab was approved for the treatment of several dermatologic immune-mediated inflammatory diseases, such as atopic dermatitis and bullous pemphigoid; whereas omalizumab is the first biological agent which was approved to treat chronic spontaneous urticaria. None of the published meta-analyses has provided the sufficient data regarding the safety of these two biologics, especially regarding their potential serious adverse events (SAEs). The aim of this study was, to comprehensively evaluate the safety of the two biologics dupilumab and omalizumab. In this study, we included 32 randomized trials, and performed meta-analyses on 113 types of SAEs regarding dupilumab and 61 types of SAEs regarding omalizumab. We identified that: (1) use of dupilumab was significantly associated with the lower incidence of atopic dermatitis, while use of omalizumab was significantly associated with the lower incidence of asthma; and (2) use of dupilumab was not significantly associated with the incidences of 112 other kinds of SAEs including various infectious diseases, while use of omalizumab was not significantly associated with the incidences of 60 other kinds of SAEs including various infectious diseases. This meta-analysis for the first time assessed the association between use of dupilumab or omalizumab and incidences of various SAEs, and identified that neither dupilumab use nor omalizumab use was associated with the increased risks of any SAEs including various infectious diseases. These findings further confirm the general safety of the two biologics dupilumab and omalizumab. This informs clinicians that there is no need to worry too much about the safety issues of these two biologics.
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Ebola disease is a lethal viral hemorrhagic fever caused by ebolaviruses within the Filoviridae family with mortality rates of up to 90%. Monoclonal antibody (mAb) based therapies have shown great potential for the treatment of EVD. However, the potential emerging ebolavirus isolates and the negative effect of decoy protein on the therapeutic efficacy of antibodies highlight the necessity of developing novel antibodies to counter the threat of Ebola. Here, 11 fully human mAbs were isolated from transgenic mice immunized with GP protein and recombinant vesicular stomatitis virus-bearing GP (rVSV-EBOV GP). These mAbs were divided into five groups according to their germline genes and exhibited differential binding activities and neutralization capabilities. In particular, mAbs 8G6, 2A4, and 5H4 were cross-reactive and bound at least three ebolavirus glycoproteins. mAb 4C1 not only exhibited neutralizing activity but no cross-reaction with sGP. mAb 7D8 exhibited the strongest neutralizing capacity. Further analysis on the critical residues for the bindings of 4C1 and 8G6 to GPs was conducted using antibodies complementarity-determining regions (CDRs) alanine scanning. It has been shown that light chain CDR3 played a crucial role in binding and neutralization and that any mutation in CDRs could not improve the binding of 4C1 to sGP. Importantly, mAbs 7D8, 8G6, and 4C1 provided complete protections against EBOV infection in a hamster lethal challenge model when administered 12 h post-infection. These results support mAbs 7D8, 8G6, and 4C1 as potent antibody candidates for further investigations and pave the way for further developments of therapies and vaccines.
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Anticuerpos Monoclonales , Anticuerpos Neutralizantes , Anticuerpos Antivirales , Modelos Animales de Enfermedad , Ebolavirus , Fiebre Hemorrágica Ebola , Animales , Ebolavirus/inmunología , Ebolavirus/genética , Anticuerpos Monoclonales/inmunología , Fiebre Hemorrágica Ebola/inmunología , Fiebre Hemorrágica Ebola/prevención & control , Fiebre Hemorrágica Ebola/virología , Anticuerpos Antivirales/inmunología , Cricetinae , Ratones , Anticuerpos Neutralizantes/inmunología , Humanos , Ratones Transgénicos , Proteínas del Envoltorio Viral/inmunología , Proteínas del Envoltorio Viral/genética , Reacciones CruzadasRESUMEN
Hydrogels are widely used as excellent drug carriers in the field of biomedicine. However, their application in medicine is limited by their poor mechanical properties and softness. To improve the mechanical properties of hydrogels, a novel triple-network amphiphilic hydrogel with three overlapping crosslinking methods using a one-pot free-radical polymerization was synthesized in this study. Temperature-sensitive and pH-sensitive monomers were incorporated into the hydrogel to confer stimulus responsiveness, making the hydrogel stimuli-responsive. The successful synthesis of the hydrogel was confirmed using techniques, such as proton nuclear magnetic resonance spectroscopy (1H NMR), Fourier-transform infrared spectroscopy (FT-IR), and X-ray diffraction (XRD). In order to compare and analyze the properties of physically crosslinked hydrogels, physically-chemically double-crosslinked hydrogels, and physically-chemically clicked triple-crosslinked hydrogels, various tests were conducted on the gels' morphology, swelling behavior, thermal stability, mechanical properties, and drug loading capacity. The results indicate that the triple-crosslinked hydrogel maintains low swelling, high mechanical strength, and good thermal stability while not significantly compromising its drug delivery capability.
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HIV-1 replication is tightly regulated in host cells, and various restriction factors have important roles in inhibiting viral replication. SAMHD1, a well-known restriction factor, suppresses HIV-1 replication by hydrolyzing intracellular dNTPs, thereby limiting the synthesis of viral cDNA in quiescent cells. In this study, we revealed an additional and distinct mechanism of SAMHD1 inhibition during the postviral cDNA synthesis stage. Using immunoprecipitation and mass spectrometry analysis, we demonstrated the interaction between SAMHD1 and MX2/MxB, an interferon-induced antiviral factor that inhibits HIV-1 cDNA nuclear import. The disruption of endogenous MX2 expression significantly weakened the ability of SAMHD1 to inhibit HIV-1. The crucial region within SAMHD1 that binds to MX2 has been identified. Notably, we found that SAMHD1 can act as a sensor that recognizes and binds to the incoming HIV-1 core, subsequently delivering it to the molecular trap formed by MX2, thereby blocking the nuclear entry of the HIV-1 core structure. SAMHD1 mutants unable to recognize the HIV-1 core showed a substantial decrease in antiviral activity. Certain mutations in HIV-1 capsids confer resistance to MX2 inhibition while maintaining susceptibility to suppression by the SAMHD1-MX2 axis. Overall, our study identifies an intriguing antiviral pattern wherein two distinct restriction factors, SAMHD1 and MX2, collaborate to establish an alternative mechanism deviating from their actions. These findings provide valuable insight into the complex immune defense networks against exogenous viral infections and have implications for the development of targeted anti-HIV therapeutics. IMPORTANCE: In contrast to most restriction factors that directly bind to viral components to exert their antiviral effects, SAMHD1, the only known deoxynucleotide triphosphate (dNTP) hydrolase in eukaryotes, indirectly inhibits viral replication in quiescent cells by reducing the pool of dNTP substrates available for viral cDNA synthesis. Our study provides a novel perspective on the antiviral functions of SAMHD1. In addition to its role in dNTP hydrolysis, SAMHD1 cooperates with MX2 to inhibit HIV-1 nuclear import. In this process, SAMHD1 acts as a sensor for incoming HIV-1 cores, detecting and binding to them, before subsequently delivering the complex to the molecular trap formed by MX2, thereby immobilizing the virus. This study not only reveals a new antiviral pathway for SAMHD1 but also identifies a unique collaboration and interaction between two distinct restriction factors, establishing a novel line of defense against HIV-1 infection, which challenges the traditional view of restriction factors acting independently. Overall, our findings further indicate the intricate complexity of the host immune defense network and provide potential targets for promoting host antiviral immune defense.
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Infecciones por VIH , VIH-1 , Proteínas de Resistencia a Mixovirus , Proteína 1 que Contiene Dominios SAM y HD , Replicación Viral , Proteína 1 que Contiene Dominios SAM y HD/metabolismo , Proteína 1 que Contiene Dominios SAM y HD/genética , Humanos , VIH-1/fisiología , VIH-1/genética , Proteínas de Resistencia a Mixovirus/metabolismo , Proteínas de Resistencia a Mixovirus/genética , Infecciones por VIH/virología , Infecciones por VIH/metabolismo , Infecciones por VIH/genética , ADN Viral/metabolismo , ADN Viral/genética , Células HEK293 , Interacciones Huésped-Patógeno , Unión ProteicaRESUMEN
We report a 42-year-old male patient who was diagnosed with acute myocardial infarction (AMI), and subsequently underwent percutaneous coronary intervention (PCI) for revascularization. The patient was transferred to the cardiac intensive care unit for intra-aortic balloon pump (IABP) due to frequent malignant arrhythmia after PCI. Then the patient experienced the most severe complications of IABP, including multiple organ embolism and intestinal necrosis. This report highlights the rare serious complications of IABP and the challenges encountered in handling this complex case.
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The Ebola virus (EBOV) is a member of the Orthoebolavirus genus, Filoviridae family, which causes severe hemorrhagic diseases in humans and non-human primates (NHPs), with a case fatality rate of up to 90%. The development of countermeasures against EBOV has been hindered by the lack of ideal animal models, as EBOV requires handling in biosafety level (BSL)-4 facilities. Therefore, accessible and convenient animal models are urgently needed to promote prophylactic and therapeutic approaches against EBOV. In this study, a recombinant vesicular stomatitis virus expressing Ebola virus glycoprotein (VSV-EBOV/GP) was constructed and applied as a surrogate virus, establishing a lethal infection in hamsters. Following infection with VSV-EBOV/GP, 3-week-old female Syrian hamsters exhibited disease signs such as weight loss, multi-organ failure, severe uveitis, high viral loads, and developed severe systemic diseases similar to those observed in human EBOV patients. All animals succumbed at 2-3 days post-infection (dpi). Histopathological changes indicated that VSV-EBOV/GP targeted liver cells, suggesting that the tissue tropism of VSV-EBOV/GP was comparable to wild-type EBOV (WT EBOV). Notably, the pathogenicity of the VSV-EBOV/GP was found to be species-specific, age-related, gender-associated, and challenge route-dependent. Subsequently, equine anti-EBOV immunoglobulins and a subunit vaccine were validated using this model. Overall, this surrogate model represents a safe, effective, and economical tool for rapid preclinical evaluation of medical countermeasures against EBOV under BSL-2 conditions, which would accelerate technological advances and breakthroughs in confronting Ebola virus disease.
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Modelos Animales de Enfermedad , Ebolavirus , Fiebre Hemorrágica Ebola , Mesocricetus , Animales , Fiebre Hemorrágica Ebola/virología , Fiebre Hemorrágica Ebola/patología , Ebolavirus/genética , Ebolavirus/patogenicidad , Femenino , Humanos , Vesiculovirus/genética , Vesiculovirus/patogenicidad , Anticuerpos Antivirales/sangre , Cricetinae , Carga Viral , Glicoproteínas/genética , Glicoproteínas/inmunologíaRESUMEN
BACKGROUND: Systemic lupus erythematosus (SLE) is a complex systemic autoimmune disease characterized by the presence of numerous autoantibodies. The interaction of infectious agents (viruses, bacteria and parasites) and a genetically susceptible host may be a key mechanism for SLE. Toxoplasma gondii is a widespread intracellular parasite that has been implicated in the pathogenesis of autoimmune diseases. However, the relationship between T. gondii infection and the increased risk of SLE in Chinese populations remains unclear. METHODS: The seroprevalence of T. gondii infection was assessed in 1771 serum samples collected from Chinese individuals (908 healthy controls and 863 SLE patients) from different regions of China using an enzyme-linked immunosorbent assay. Serum autoantibodies and clinical information were obtained and analysed. RESULTS: Our observations revealed a higher prevalence of anti-T. gondii antibodies (ATxA) immunoglobulin G (IgG) in serum samples from SLE patients (144/863, 16.7%) than in those from the healthy controls (53/917, 5.8%; P < 0.0001), indicating a 2.48-fold increased risk of SLE in the ATxA-IgG+ population, after adjustment for age and sex (95% confidence interval [CI] 1.70-3.62, P < 0.0001). ATxA-IgG+ SLE patients also showed a 1.75-fold higher risk of developing moderate and severe lupus symptoms (95% CI 1.14-2.70, P = 0.011) compared to ATxA-IgG- patients. Relative to ATxA-IgG- patients, ATxA-IgG+ patients were more likely to develop specific clinical symptoms, including discoid rash, oral ulcer, myalgia and alopecia. Seven antibodies, namely anti-ribosomal RNA protein (rRNP), anti-double stranded DNA (dsDNA), anti-cell membrane DNA (cmDNA), anti-scleroderma-70 (Scl-70), anti-cardiolipin (CL), anti-beta2-glycoprotein-I (B2GPI) and rheumatoid factor (RF), occurred more frequently in ATxA-IgG+ patients. When combined with anti-dsDNA and RF/anti-rRNP/anti-cmDNA/ESR, ATxA-IgG significantly increased the risk for severe lupus. CONCLUSIONS: Our results suggest that ATxA-IgG may be a significant risk factor for SLE prevalence and severity in Chinese populations.
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Autoanticuerpos , Lupus Eritematoso Sistémico , Humanos , Estudios Seroepidemiológicos , Prevalencia , Lupus Eritematoso Sistémico/complicaciones , Lupus Eritematoso Sistémico/epidemiología , Inmunoglobulina G , Factores de Riesgo , ADNRESUMEN
Macroautophagy/autophagy is a conserved process in eukaryotic cells to degrade and recycle damaged intracellular components. Higher level of autophagy in the brain has been observed, and autophagy dysfunction has an impact on neuronal health, but the molecular mechanism is unclear. In this study, we showed that overexpression of Toll-1 and Toll-7 receptors, as well as active Spätzle proteins in Drosophila S2 cells enhanced autophagy, and Toll-1/Toll-7 activated autophagy was dependent on Tube-Pelle-PP2A. Interestingly, Toll-1 but not Toll-7 mediated autophagy was dMyd88 dependent. Importantly, we observed that loss of functions in Toll-1 and Toll-7 receptors and PP2A activity in flies decreased autophagy level, resulting in the loss of dopamine (DA) neurons and reduced fly motion. Our results indicated that proper activation of Toll-1 and Toll-7 pathways and PP2A activity in the brain are necessary to sustain autophagy level for DA neuron survival.
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Following the successful control of poliovirus, the re-emergence of respiratory enterovirus D68 (EV-D68), a prominent non-polio enterovirus, has become a serious public health concern worldwide. Host innate immune responses are the primary defense against EV-D68 invasion; however, the mechanism underlying viral evasion of the antiviral activity of interferons (IFN) remains unclear. In this study, we found that EV-D68 inhibited type I IFN signaling by cleaving signal transducer and activator of transcription 1 (STAT1), a crucial factor in cellular responses to interferons and other cytokines. We observed that the prototype and circulating EV-D68 strains conserved their ability to induce STAT1 cleavage and attenuate IFN signal transduction. Further investigation revealed that EV-D68 3C protease cleaves STAT1 at the 131Q residue. Interestingly, not all enterovirus-encoded 3C proteases exhibited this ability. EV-D68 and poliovirus 3C proteases efficiently induced STAT1 cleavage; whereas, 3C proteases from EV-A71, coxsackievirus A16, and echoviruses did not. STAT1 cleavage also abolished the nuclear translocation capacity of STAT1 in response to IFN stimulation to activate downstream signaling elements. Overall, these results suggest that STAT1, targeted by viral protease 3C, is utilized by EV-D68 to subvert the host's innate immune response.IMPORTANCEEnterovirus D68 (EV-D68) has significantly transformed over the past decade, evolving from a rare pathogen to a potential pandemic pathogen. The interferon (IFN) signaling pathway is an important defense mechanism and therapeutic target for the host to resist viral invasion. Previous studies have reported that the EV-D68 virus blocks or weakens immune recognition and IFN production in host cells through diverse strategies; however, the mechanisms of EV-D68 resistance to IFN signaling have not been fully elucidated. Our study revealed that EV-D68 relies on its own encoded protease, 3C, to directly cleave signal transducer and activator of transcription 1 (STAT1), a pivotal transduction component in the IFN signaling pathway, disrupting the IFN-mediated antiviral response. Previous studies on human enteroviruses have not documented direct cleavage of the STAT1 protein to evade cellular immune defenses. However, not all enteroviral 3C proteins can cleave STAT1. These findings highlight the diverse evolutionary strategies different human enteroviruses employ to evade host immunity.
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Proteasas Virales 3C , Enterovirus Humano D , Interferón Tipo I , Transducción de Señal , Humanos , Proteasas Virales 3C/metabolismo , Antígenos Virales/metabolismo , Antivirales/farmacología , Cisteína Endopeptidasas/metabolismo , Enterovirus Humano D/fisiología , Interacciones Huésped-Patógeno , Evasión Inmune , Inmunidad Innata , Interferón Tipo I/metabolismo , Péptido Hidrolasas/metabolismo , Proteolisis , Factor de Transcripción STAT1/metabolismo , Proteínas Virales/metabolismoRESUMEN
Stimulus-responsive hydrogels have been widely used in the field of drug delivery because of their three-dimensional pore size and the ability to change the drug release rate with the change in external environment. In this paper, the temperature-sensitive monomer 2-methyl-2-acrylate-2-(2-methoxyethoxy-ethyl) ethyl ester (MEO2MA) and oligoethylene glycol methyl ether methacrylate (OEGMA) as well as the pH-sensitive monomer N,N-Diethylaminoethyl methacrylate (DEAEMA) were used to make the gel with temperature and pH response. Four kinds of physicochemical double-crosslinked amphiphilic co-network gels with different polymerization degrees were prepared by the one-pot method using the stereocomplex between polylactic acid as physical crosslinking and click chemistry as chemical crosslinking. By testing morphology, swelling, thermal stability and mechanical properties, the properties of the four hydrogels were compared. Finally, the drug release rate of the four gels was tested by UV-Vis spectrophotometer. It was found that the synthetic hydrogels had a good drug release rate and targeting, and had great application prospect in drug delivery.
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Medical titanium alloy Ti-6Al-4V (TC4) has been widely used in the medical field, especially in human tissue repair. However, TC4 has some shortcomings, which may cause problems with biocompatibility and mechanical compatibility in direct contact with the human body. To solve this problem, physical gels are formed on the surface of TC4, and the storage modulus of the formed physical gel matches that of the human soft tissue. 2-bromoisobutyryl bromide (BIBB) and dopamine (DA) were used to form initiators on the surface of hydroxylated medical titanium alloy. Different initiators were formed by changing the ratio of BIBB and DA, and the optimal one was selected for subsequent reactions. Under the action of the catalyst, L-lactide and D-lactide were ring-opened polymerized with hydroxyethyl methacrylate (HEMA), respectively, to form macromolecular monomers HEMA-PLLA29 and HEMA-PDLA29 with a polymerization degree of 29. The two macromolecular monomers were stereo-complexed by ultrasound to form HEMA-stereocomplex polylactic acid (HEMA-scPLA29). Based on two monomers, 2-(2-methoxyethoxy) ethyl methacrylate (MEO2MA) and oligo (ethylene oxide) methacrylate (OEGMA), and the physical crosslinking agent HEMA-scPLA29, physical gels are formed on the surface of TC4 attached to the initiator via Atom Transfer Radical Addition Reaction (ATRP) technology. The hydrogels on the surface of titanium alloy were characterized and analyzed by a series of instruments. The results showed that the storage modulus of physical glue was within the range of the energy storage modulus of human soft tissue, which was conducive to improving the mechanical compatibility of titanium alloy and human soft tissue.
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20E-hydroxyecdysone (20E) plays important roles in larval molting and metamorphosis in insects and is also involved in the insect innate immune response. Insect metamorphosis is a highly successful strategy for environmental adaptation and is the most vulnerable stage during which the insect is susceptible to various pathogens. 20E regulates a series of antimicrobial peptides (AMPs) through the immunodeficiency (IMD) pathway activation in Drosophila; nevertheless, whether other immune pathways are involved in 20E-regulated insect immunity is unknown. Our previous studies showed that BmMD-2A is a member of the MD-2-related lipid recognition (ML) family of proteins that are involved in the Bombyx mori innate immunity Toll signaling pathway. In this study, we further demonstrate that BmMD-2A is also positively regulated by 20E, and the BmMD-2A neutralization experiment suggested that 20E activates some downstream immune effect factors, the AMP genes against Escherichia coli and Staphylococcus aureus, through the regulation of BmMD-2A in larval metamorphosis, implying that B. mori may use the Toll-ML signaling pathway to maintain innate immune balance in the larval-pupal metamorphosis stage, which is a different innate immunity pathway regulated by 20E compared to the IMD pathway in Drosophila.
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Bombyx , Ecdisterona , Animales , Ecdisterona/metabolismo , Bombyx/metabolismo , Pupa/metabolismo , Proteínas de Insectos/genética , Proteínas de Insectos/metabolismo , Metamorfosis Biológica/genética , Escherichia coli , Larva/metabolismo , Inmunidad Innata , Drosophila/metabolismoRESUMEN
BACKGROUND: The spine is the most frequently affected part of the skeletal system to metastatic tumors. External radiotherapy is considered the first-line standard of care for these patients with spine metastases. Recurrent spinal metastases after radiotherapy cannot be treated with further radiotherapy within a short period of time, making treatment difficult. We aimed to evaluate the effectiveness and safety of MWA combined with cementoplasty in the treatment of spinal metastases after radiotherapy under real-time temperature monitoring. METHODS: In this retrospective study, 82 patients with 115 spinal metastatic lesions were treated with MWA and cementoplasty under real-time temperature monitoring. Changes in visual analog scale (VAS) scores, daily morphine consumption, and Oswestry Disability Index (ODI) scores were noted. A paired Student's t-test was used to assess these parameters. Complications during the procedure were graded using the CTCAE version 5.0. RESULTS: Technical success was attained in all patients. The mean VAS score was 6.3 ± 2.0 (range, 4-10) before operation, and remarkable decline was noted in one month (1.7 ± 1.0 [P < .001]), three months (1.4 ± 0.8 [P < .001]), and six months (1.3 ± 0.8 [P < .001]) after the operation. Significant reductions in daily morphine consumption and ODI scores were also observed (P < .05). Cement leakage was found in 27.8% (32/115) of lesions, with no obvious associated symptoms. CONCLUSION: MWA combined with cementoplasty under real-time temperature monitoring is an effective and safe method for recurrent spinal metastases after radiotherapy.
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Cementoplastia , Neoplasias de la Columna Vertebral , Humanos , Microondas/uso terapéutico , Estudios Retrospectivos , Neoplasias de la Columna Vertebral/diagnóstico por imagen , Neoplasias de la Columna Vertebral/radioterapia , Temperatura , Derivados de la MorfinaRESUMEN
Organic molecules which can undergo excited-state intramolecular proton transfer (ESIPT) process have been considered as ideal gain materials for near-infrared organic lasers owing to their effective four-level systems. However, extending lasing wavelength beyond 800â nm with present ESIPT-active gain materials is still in challenge. Herein, we established a molecular design strategy that operates via extending the π-conjugated system of the ESIPT parent core to enhance the cascaded double ESIPT process and thus to achieve the red-shifted six-level system lasing. Concretely, a model molecule with 1,9-dihydroxyanthracene as the ESIPT parent core was designed and synthesized, which was proved to undergo twice cascaded ESIPT processes while the 1,8-dihydroxynaphthalene-based analogue can only undergo once ESIPT process based on DFT calculations and ultrafast dynamics analyses. Finally, a six-level system lasing toward 900â nm was achieved with a low threshold of 27.4â µJ cm-2 .
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Hydrogel is a good drug carrier, widely used in the sustained-release aspect of tumor drugs, which can achieve the continuous release of drugs to the tumor sites. In this study, diethylene glycol monomethyl ether methacrylate (MEO2MA) and poly (ethylene glycol) methyl ether methacrylate (OEGMA) are temperature-sensitive monomers. N-Methacryloyl-L-Histidine (Mist) is pH sensitive monomer and ligand for metal coordination bond. The temperature-sensitive monomers and pH sensitive monomer with stereocomplex of modified polylactic acid (HEMA-PLLA30/PDLA30) were mixed, under 2,2'-azobis (2-methylpropionitrile) (AIBN) as radical initiator, polymer was formed by free-radical polymerization. The polymer was then immersed in ZnSO4 solution, the imidazole group of Mist monomer forms a tridentate metal coordination bond with Zn2+, temperature/pH double-responsive and physical double-crosslinked hydrogel was finally obtained. Comparing the hydrogen bond hydrogel, hydrogen bond and metal coordination bond double crosslinking hydrogel, metal coordination bond hydrogel, testing thermal stability, viscoelasticity, swelling, and morphology of three hydrogels. In addition, using UV-Visible spectroscopy (UV-Vis) to test the sustained release of the hydrophobic drug doxorubicin hydrochloride (DOX-HCl) in the human tumor environment (37 °C, pH = 5). We found that the temperature/pH double-responsive and physical double-crosslinked hydrogel had the most potential for the sustained drug release.
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Medical titanium alloy Ti-6Al-4V (TC4) is an ideal surgical implant material for human tissue repair and replacement. TC4 implantation will be in close contact with human soft tissue and has mechanical compatibility problems. In order to solve this problem, the hydrogel was formed on the surface of TC4 by utilizing the adhesion of dopamine, and the storage modulus of the formed hydrogel matched that of human soft tissue. In this paper, the surface of TC4 was first modified with dopamine (DA) and 2-bromoisobutyryl bromide (BIBB). 2-(2-methoxyethoxy) ethyl methacrylate (MEO2MA), oligo (ethylene oxide) methacrylate (OEGMA) and 2-methacryloyloxyethyl phosphorylcholine (MPC) are used as monomers, and methylenebisacrylamide (MBA) is used as cross-linking agent. Thermosensitive hydrogels were formed on the surface of modified TC4 by the ATRP technique. The successful synthesis of initiator and hydrogels on TC4 was demonstrated by Fourier transform infrared (FT-IR) and X-ray photoelectron spectroscopy (XPS). The morphology of the hydrogel was observed by the scanning electron microscope (SEM), and the water absorption and temperature sensitivity were investigated by the swelling property. The thermal and mechanical properties of these gels were measured using thermal analysis system (TAS) and dynamic mechanical analyzer (DMA). The results show that the hydrogel on TC4 has good thermal stability and storage modulus that matches human soft tissue.
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BACKGROUND: Brush cutters are widely used in Chinese landscape gardening and agricultural laboring which leads the operators being exposed to many risks. Low back pain (LBP) is particularly common and can lead to substantial personal, community and financial burdens. The aim of the presented study was to measure the activity and function of each torso muscle of the operator when using the bush cutter, so as to evaluate the muscle injury of the operator during using several common brush cutters for different landscape tasks. MATERIAL AND METHODS: The human postures of 6 workers using 2 types of brush cutters in the 3 working conditions were recorded and measured by using a surface electromyography (sEMG) system and a camera. The test results were compared by t-test and sign test. The effect of human posture on the sEMG signal of trunk muscles in different working condition were analyzed by ANOVA. RESULTS: In the 3 working conditions, except for the left trapezius muscle, the muscle load of operating the backpack brush cutter is higher than that of operating side-mounted brush cutter. When operating the side-mounted backpack brush cutter, the force on both sides of the trapezius muscle is uneven, the load of the left trapezius muscle is >25%, and the maximum value is >30%. CONCLUSIONS: The results highlighted significant differences in the effects of different working postures on the muscle activities of workers' trunk. Safe operation standards should therefore be taken to protect the exposed workers and to improve the industrial design of irrigation cutters to prevent the occurrence of occupational diseases. Med Pr. 2022;73(3):201-7.
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Jardinería , Fatiga Muscular , Electromiografía , Humanos , Fatiga Muscular/fisiología , Músculo Esquelético/fisiología , Postura/fisiologíaRESUMEN
Purpose: To evaluate the safety and efficacy of stereotactic ablative brachytherapy (SABT) as a salvage therapy for patients with recurrent chest wall cancer (rCWC) who have previously received external beam radiotherapy (EBRT) or surgery. Materials and methods: Between November 2013 and October 2020, a total of 130 patients (including 75 men with a median age of 63 years) with rCWC treated with SABT were enrolled in this multicenter retrospective study. There were 97 cases of non-small-cell lung carcinoma, 24 cases of breast cancer, and 9 cases of thymic cancer. Of the patients included, 102 patients previously received surgery and 58 patients received EBRT, with systemic treatment progressing after recurrence. None of them were suitable or refused to undergo salvage EBRT or surgery again. Results: During the 22 (4-70)-month median patient follow-up, 59 patients died. The local control (LC) rates at 6, 12, 24, and 36 months were 88.3%, 74.3%, 50.4%, and 36.7%, respectively. The 1-, 2- and 3-year survival rates were 85%, 56%, and 42%, respectively. The median overall survival was 26 months (95% CI, 18.9-33.1 months). The pain relief rate was 81%, and the median to remission time was 10 days. Univariate and multivariate analyses showed that independent prognostic factors for LC included tumor size and postoperative D90. On the other hand, independent prognostic factors for survival include the Karnofsky performance status (KPS) score, tumor size, and D90 19 patients (14.6%) developed grade I/II skin reaction complications. No grade III or severer complications occurred. Conclusion: SABT is safe and effective as a salvage therapy for rCWC following EBRT/surgery. For patients with a KPS score greater than 80, prescribed dose greater than 130 Gy, and tumor size less than 4 cm may bring better results.