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AIM: This study aims to evaluate the safety and analgesic efficacy of pre-mixed nitrous oxide/oxygen mixture treatment of pain induced by dressing change for perianal abscess. DESIGN: This protocol is a randomized, double-blind, placebo-controlled trial. METHODS: This study will be implemented in the Hospital of Traditional Chinese Medicine. Subjects enrolled in this study are hospitalized patients who suffered from moderate to severe pain due to dressing change after incision and drainage. Two hundred patients will be selected and randomly assigned to either an intervention or a control group. The intervention group will get routine pain treatment plus pre-mixed nitrous oxide/oxygen mixture treatment and the control group will be treated with routine pain management plus medical air treatment. All these patients, medical staff and investigators are blind to the nature of the gas in each cylinder, which is randomized. Data will be collected at baseline (T0), 5 min (T1) after the starting of intervention and 5 min post intervention (T2) for each group. The primary outcome is the level of pain relief at T1 and T2. The secondary outcomes cover physiological parameters, adverse events, satisfaction of patients and health professionals and the acceptance from patients. DISCUSSION: Results of this study will be discussed and the safety and effect of nitrous oxide/oxygen treatment of pain induced by dressing change will be proven. IMPACT: When the finding of this study has an active effect on the treatment of pain caused by dressing change, it may provide more options for nursing staff to choose nurse-led analgesia techniques and then improving the level and quality of pain care as well as patients' overall satisfaction with the Anorectal Department in China.
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Absceso , Óxido Nitroso , Absceso/terapia , Vendajes , China , Método Doble Ciego , Humanos , Oxígeno , Dolor/tratamiento farmacológico , Dolor/etiología , Dimensión del Dolor , Ensayos Clínicos Controlados Aleatorios como Asunto , Resultado del TratamientoRESUMEN
OBJECTIVE: To quantitatively detect GNAQ/11 mutations in uveal melanoma (UM) by droplet digital PCR (ddPCR). METHODS: Formaldehyde-fixed paraffin-embedded (FFPE) tumor samples were taken from 78 UM patients with enucleation in West China Hospital between 2009 and 2015. None of the patients received radiotherapy or chemotherapy before enucleation. A retrospective study was conducted to detect GNAQ/11 mutation in UM by ddPCR. To compare the consistency of the results of the two detection methods, DNA sequencing was performed on the target gene by Sanger sequencing. 78 patients with UM were studied retrospectively. GNAQ/11 mutations in uveal melanoma was detected by ddPCR. The consistency of the results of the two detection methods was analyzed. RESULTS: GNAQ/11 mutations frequency was 91.9%. The consistency test between Sanger sequencing and ddPCR of GNAQ/11 mutations in 74 patients with UM was conducted. Kappa coefficient=0.436, P=0.001. The error rate of Sanger sequencing results was significantly higher in the heterogeneous group than in the homogeneous group (12/37 vs. 3/16, P=0.53), but the difference was not statistically significant. CONCLUSION: The results of ddPCR and Sanger sequencing showed good consistency, and the mutation ratio of GNAQ/11 in UM was significantly different. GNAQ/11 mutation frequency in UM patients detected by ddPCR was close to the reported frequency. It is more recommended to use ddPCR with high sensitivity to detect gene mutations in samples of tumor tissue DNA derived from FFPE. Sanger sequencing is prone to false negative results.
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Subunidades alfa de la Proteína de Unión al GTP Gq-G11 , Subunidades alfa de la Proteína de Unión al GTP , Melanoma , Mutación , Reacción en Cadena de la Polimerasa , Neoplasias de la Úvea , China , ADN/química , Análisis Mutacional de ADN , Subunidades alfa de la Proteína de Unión al GTP/genética , Subunidades alfa de la Proteína de Unión al GTP/metabolismo , Subunidades alfa de la Proteína de Unión al GTP Gq-G11/genética , Subunidades alfa de la Proteína de Unión al GTP Gq-G11/metabolismo , Humanos , Melanoma/diagnóstico , Melanoma/genética , Estudios Retrospectivos , Neoplasias de la Úvea/diagnóstico , Neoplasias de la Úvea/genéticaRESUMEN
BACKGROUND: Acute pain is the most common complaint in Emergency Department (ED) admissions, and options for analgesia are limited. Nitrous oxide/oxygen possesses many properties showing it may be an ideal analgesic in the ED. OBJECTIVES: The aim of this study is to evaluate the safety and analgesic effect of the fixed nitrous oxide/oxygen mixture for trauma patients in the ED. METHODS: We enrolled 60 patients in this double-blind, randomized study. The treatment group received conventional pain treatment plus a mixture of 65% nitrous oxide/oxygen. The control group received the conventional pain treatment plus oxygen. Primary outcome was the reduction in pain intensity at 5 and 15 min after the start of intervention. Secondary outcomes include adverse events, physiological parameters, and satisfaction from both patients and health care professionals. RESULTS: Initial pain scores for the nitrous oxide/oxygen group (6.0 [5.0-8.0]) and the oxygen group (6.75 [5.0-9.0]) were comparable (p = 0.57). The mean numerical rating scale scores at 5 min were 3.4 ± 1.8 and 7.0 ± 1.8 for nitrous oxide/oxygen and oxygen, respectively (p < 0.01). The mean pain intensity at 15 min in the treatment group was 3.0 ± 1.9, compared with 6.3 ± 2.2 in the control group (p < 0.01). Both patients' (8.0 [7.0-9.0] vs. 4.0 [2.0-6.0], p < 0.01) and physicians' (8.5 [8.0-9.0] vs. 4.0 [3.0-6.0], p < 0.01) satisfaction scores in the treatment group were significantly higher than the oxygen group. No serious adverse events were observed. CONCLUSIONS: This study gives supporting evidence for the safety and effectiveness of using self-administered nitrous oxide/oxygen mixture in the ED for moderate-to-severe traumatic pain.
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Analgésicos/normas , Óxido Nitroso/farmacología , Oxígeno/farmacología , Manejo del Dolor/normas , Heridas y Lesiones/tratamiento farmacológico , Dolor Agudo/tratamiento farmacológico , Adulto , Analgésicos/uso terapéutico , Método Doble Ciego , Combinación de Medicamentos , Servicio de Urgencia en Hospital/organización & administración , Servicio de Urgencia en Hospital/estadística & datos numéricos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Óxido Nitroso/uso terapéutico , Oxígeno/uso terapéutico , Manejo del Dolor/métodos , Manejo del Dolor/estadística & datos numéricos , Dimensión del Dolor/métodos , Satisfacción del Paciente , Resultado del Tratamiento , Heridas y Lesiones/complicacionesRESUMEN
As a new type of heterogeneous catalyst with "homogeneous-like" activity, single-site transition-metal materials are usually treated as integrated but separate active centers. A novel grouping effect is reported for single Ni-N4 sites in nitrogen-doped carbon (Ni/NC), where an effective ligand-stabilized polycondensation method endows Ni/NC nanocatalysts with a high content of single-site Ni up to 9.5â wt %. The enhanced electron density at each single Ni-N4 site promotes a highly efficient hydrogen transfer, which is exemplified by the coupling of benzyl alcohol and aniline into N-benzylaniline with a turnover frequency (TOF) value of 7.0â molN-benzylaniline molmetal -1 h-1 ; this TOF outpaces that of reported stable non-noble-metal-based catalysts by a factor of 2.
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The exploitation of metal-free organic polymers as electrodes for water splitting reactions is limited by their presumably low activity and poor stability, especially for the oxygen evolution reaction (OER) under more critical conditions. Now, the thickness of a cheap and robust polymer, poly(p-phenylene pyromellitimide) (PPPI) was rationally engineered by an inâ situ polymerization method to make the metal-free polymer available for the first time as flexible, tailorable, efficient, and ultra-stable electrodes for water oxidation over a wide pH range. The PPPI electrode with an optimized thickness of about 200â nm provided a current density of 32.8â mA cm-2 at an overpotential of 510â mV in 0.1â mol L-1 KOH, which is even higher than that (31.5â mA cm-2 ) of commercial IrO2 OER catalyst. The PPPI electrodes are scalable and stable, maintaining 92 % of its activity after a 48-h chronoamperometric stability test.
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Due to the low solubility and swelling properties of chitin bis(arylcarbamate) in most organic solvents, the chiral stationary phases (CSPs) prepared from chitin derivatives can be analyzed with a wide range of solvents. In order to develop new CSPs of chitin derivatives with halogen groups, chitin was derivatized with three different phenyl isocyanates to obtain chitin bis(4-trifluoromethoxyphenylcarbamate), chitin bis(3-chloro-4-methylphenylcarbamate) and chitin bis(4-chloro-3-trifluoromethylphenylcarbamate). Then, the three chitin derivatives were coated on macroporous 3-aminopropyl-functionalized silica gel to obtain three CSPs 1-3 respectively. These CSPs showed good enantioseparation capabilities towards tadalafil and its intermediate. Therefore, these CSPs are potentially applied for the enantioseparation and determination of tadalafil and its intermediate. It was also found that the retention times of some enantiomers were prolonged in the presence of their diastereoisomers or structural analogues and as a result, the resolution was improved to some extent. Hence, in the enantioseparation of a compound with two chiral centers, the resolution is hopefully improved by adding a diastereoisomer or a structural analogue.
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Quitina/química , Tadalafilo/química , Cromatografía Líquida de Alta Presión/instrumentación , Solubilidad , Solventes/química , EstereoisomerismoRESUMEN
Membranous nephropathy (MN) is a leading cause of nephrotic syndrome in adults and a significant cause of end-stage renal disease, yet current therapies are nonspecific, toxic, and often ineffective. The development of novel targeted therapies requires a detailed understanding of the pathogenic mechanisms, but progress is hampered by the lack of a robust mouse model of disease. We report that DBA/1 mice as well as congenic FcγRIII(-/-) and FcRγ(-/-) mice immunized with a fragment of α3(IV) collagen developed massive albuminuria and nephrotic syndrome, because of subepithelial deposits of mouse IgG and C3 with corresponding basement membrane reaction and podocyte foot process effacement. The clinical presentation and histopathologic findings were characteristic of MN. Although immunized mice produced genuine anti-α3NC1 autoantibodies that bound to kidney and lung basement membranes, neither crescentic glomerulonephritis nor alveolitis ensued, likely because of the predominance of mouse IgG1 over IgG2a and IgG2b autoantibodies. The ablation of activating IgG Fc receptors did not ameliorate injury, implicating subepithelial deposition of immune complexes and consequent complement activation as a major effector pathway. We have thus established an active model of murine MN. This model, leveraged by the availability of genetically engineered mice and mouse-specific reagents, will be instrumental in studying the pathogenesis of MN and evaluating the efficacy of novel experimental therapies.
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Autoantígenos/toxicidad , Colágeno Tipo IV/toxicidad , Modelos Animales de Enfermedad , Glomerulonefritis Membranosa/inmunología , Síndrome Nefrótico/etiología , Albuminuria/etiología , Albuminuria/inmunología , Animales , Autoanticuerpos/inmunología , Autoantígenos/inmunología , Membrana Basal/inmunología , Colágeno Tipo IV/inmunología , Complemento C3/inmunología , Glomerulonefritis Membranosa/complicaciones , Inmunización , Inmunoglobulina G/inmunología , Riñón/inmunología , Riñón/patología , Riñón/fisiopatología , Ratones , Ratones Congénicos , Ratones Endogámicos DBA , Síndrome Nefrótico/inmunología , Alveolos Pulmonares/inmunología , Receptores de IgG , Proteínas Recombinantes de Fusión/inmunología , Proteínas Recombinantes de Fusión/toxicidadRESUMEN
BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is a highly fatal disease with limited effective treatment especially after first-line chemotherapy. The human epidermal growth factor receptor 2 (HER-2) immunohistochemistry (IHC) positive is associated with more aggressive clinical behavior and shorter overall survival in PDAC. CASE SUMMARY: We present a case of multiple metastatic PDAC with IHC mismatch repair proficient but HER-2 IHC weakly positive at diagnosis that didn't have tumor regression after first-line nab-paclitaxel plus gemcitabine and PD-1 inhibitor treatment. A novel combination therapy PRaG 3.0 of RC48 (HER2-antibody-drug conjugate), radiotherapy, PD-1 inhibitor, granulocyte-macrophage colony-stimulating factor and interleukin-2 was then applied as second-line therapy and the patient had confirmed good partial response with progress-free-survival of 6.5 months and overall survival of 14.2 month. She had not developed any grade 2 or above treatment-related adverse events at any point. Percentage of peripheral CD8+Temra and CD4+Temra were increased during first two activation cycles of PRaG 3.0 treatment containing radiotherapy but deceased to the baseline during the maintenance cycles containing no radiotherapy. CONCLUSION: PRaG 3.0 might be a novel strategy for HER2-positive metastatic PDAC patients who failed from previous first-line approach and even PD-1 immunotherapy but needs more data in prospective trials.
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Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Receptor ErbB-2 , Humanos , Femenino , Gemcitabina , Desoxicitidina/uso terapéutico , Estudios Prospectivos , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Paclitaxel/uso terapéutico , Neoplasias Pancreáticas/tratamiento farmacológico , Carcinoma Ductal Pancreático/tratamiento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Albúminas/uso terapéuticoRESUMEN
BACKGROUND: Patients with hematological malignancies received multiple hypodermic injections of recombinant human granulocyte colony-stimulating factor. Procedural pain is one of the most common iatrogenic causes of pain in patients with hematological malignancies. It is also identified as the most commonly occurring problem in clinical care in the Department of Hematology and Oncology at Shenzhen University General Hospital. However, providing immediate relief from pain induced by hypodermic injection of recombinant human granulocyte colony-stimulating factor remains a major challenge. This trial aims to evaluate the safety and analgesic efficacy of a fixed nitrous oxide/oxygen mixture for patients with hematological malignancies and experiencing procedural pain caused by hypodermic injection of recombinant human granulocyte colony-stimulating factor in the department. METHODS: The nitrous oxide/oxygen study is a single-center, randomized, double-blind, placebo-controlled trial involving patients with hematological malignancies who require hypodermic injections of recombinant human granulocyte colony-stimulating factor for treatment. This trial was conducted in the Hematology and Oncology Department of Shenzhen University General Hospital. A total of 54 eligible patients were randomly allocated to either the fixed nitrous oxide/oxygen mixture group (n = 36) or the oxygen group (n = 18). Neither the investigators nor the patients known about the randomization list and the nature of the gas mixture in each cylinder. Outcomes were monitored at the baseline (T0), immediately after hypodermic injection of recombinant human granulocyte colony-stimulating factor (T1), and 5 min after hypodermic injection of recombinant human granulocyte colony-stimulating factor (T2) for each group. The primary outcome measure was the score in the numerical rating scale corresponding to the highest level of pain experienced during hypodermic injection of recombinant human granulocyte colony-stimulating factor. Secondary outcomes included the fear of pain, anxiety score, four physiological parameters, adverse effects, total time of gas administration, satisfaction from both patients and nurses, and the acceptance of the patients. DISCUSSION: This study focused on the safety and analgesic efficacy during hypodermic injection of recombinant human granulocyte colony-stimulating factor procedure. Data on the feasibility and safety of nitrous oxide/oxygen therapy was provided if proven beneficial to patients with hematological malignancies during hypodermic injection of recombinant human granulocyte colony-stimulating factor and widely administered to patients with procedural pain in the department. TRIAL REGISTRATION: Chinese Clinical Trial Register, ChiCTR2200061507. Registered on June 27, 2022. http://www.chictr.org.cn/edit.aspx?pid=170573&htm=4.
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Neoplasias Hematológicas , Dolor Asociado a Procedimientos Médicos , Humanos , Óxido Nitroso/efectos adversos , Oxígeno/uso terapéutico , Manejo del Dolor/métodos , Resultado del Tratamiento , Dolor/diagnóstico , Dolor/tratamiento farmacológico , Dolor/etiología , Analgésicos/uso terapéutico , Método Doble Ciego , Neoplasias Hematológicas/complicaciones , Factor Estimulante de Colonias de Granulocitos/efectos adversos , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
OBJECTIVE: To construct a novel nomogram model that predicts the risk of hyperuricemia incidence in IgA nephropathy (IgAN). METHODS: Demographic and clinicopathological characteristics of 1184 IgAN patients in the First Affiliated Hospital of Zhengzhou University Hospital were collected. Univariate analysis and multivariate logistic regression were used to screen out hyperuricemia risk factors. The risk factors were used to establish a predictive nomogram model. The performance of the nomogram model was evaluated using an area under the receiver-operating characteristic curve (AUC), calibration plots, and a decision curve analysis. RESULTS: Independent predictors for hyperuricemia incidence risk included sex, hypoalbuminemia, hypertriglyceridemia, blood urea nitrogen (BUN), estimated glomerular filtration rate (eGFR), 24 h urinary protein (24 h TP), gross hematuria and tubular atrophy/interstitial fibrosis (T). The nomogram model exhibited moderate prediction ability with an AUC of 0.834 (95% CI 0.804-0.864). The AUC from validation reached 0.787 (95% CI 0.736-0.839). The decision curve analysis displayed that the hyperuricemia risk nomogram was clinically applicable. CONCLUSION: Our novel and simple nomogram containing 8 factors may be useful in predicting hyperuricemia incidence risk in IgAN.
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Glomerulonefritis por IGA , Hiperuricemia , Humanos , Adulto , Glomerulonefritis por IGA/complicaciones , Glomerulonefritis por IGA/epidemiología , Hiperuricemia/complicaciones , Hiperuricemia/epidemiología , Modelos Estadísticos , Pronóstico , Estudios Retrospectivos , NomogramasRESUMEN
Angiogenesis is essential for the growth and metastasis of several malignant tumors including colorectal cancer (CRC). The molecular mechanism underlying CRC angiogenesis has not been fully elucidated. Emerging evidence indicates that secreted microRNAs (miRNAs) may mediate the intercellular communication between tumor cells and neighboring endothelial cells to regulate tumor angiogenesis. In addition, exosomes have been shown to carry and deliver miRNAs to regulate angiogenesis. miRNA N-72 is a novel miRNA that plays a regulatory role in the EGF-induced migration of human amnion mesenchymal stem cells. However, the relation between miRNA N-72 and cancer remains unclear. We here found that CRC cells could secrete miRNA N-72. A high miRNA N-72 level was detected in the serum of CRC patients and the cultured CRC cells. Moreover, the CRC cell-secreted miRNA N-72 could promote the migration, tubulogenesis, and permeability of endothelial cells. In addition, the mouse xenograft model was used to verify the facilitating effects of miRNA N-72 on CRC growth, angiogenesis, and metastasis in vivo. Further mechanism analysis revealed that CRC cell-secreted miRNA N-72 could be delivered into endothelial cells via exosomes, which then inhibited cell junctions of endothelial cells by targeting CLDN18 and consequently promoted angiogenesis. Our findings reveal a novel mechanism of CRC angiogenesis and highlight the potential of secreted miRNA N-72 as a therapeutic target and a biomarker for CRC.
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OBJECTIVE: The relationship between hyperuricemia and IgA nephropathy (IgAN) was evaluated systematically in this research. METHODS: The Preferred Reporting Items for Systematic Review and Meta-analysis statement was employed to design and report the study. RESULTS: Twenty-five studies were included in this meta-analysis with a total of 6048 IgAN patients. The clinical indicators indicated that blood urea nitrogen (BUN) (p < 0.00001, mean difference (MD) = 2.60, 95% confidence interval (CI) 1.74-3.46), serum creatinine (Scr) (p < 0.00001, MD = 44.56, 95% CI 31.15-57.98), diastolic blood pressure(DBP) (p < 0.00001, MD = 3.86, 95% CI 2.84-4.88), systolic blood pressure(SBP) (p < 0.00001, MD = 6.71, 95% CI 4.70-8.71), and 24-h urine protein(24 h TP) (p < 0.00001, MD = 0.76, 95% CI 0.58-0.94) were significantly increased in IgAN with hyperuricemia group than that in normouricemic IgAN group. The pathological analysis indicated that mesangial proliferation (p < 0.00001, MD = 0.12, 95% CI 0.07-0.17), vascular lesion (p < 0.00001, MD = 0.17, 95% CI 0.13-0.20), segmental lesion (p < 0.00001, MD = 0.15, 95% CI 0.03-0.26), tubulointerstitial damage (p < 0.00001, MD = 1.27, 95% CI 1.06-1.48), and glomerulosclerosis (p < 0.00001, MD = 0.56, 95% CI 0.40-0.72) were considerably climbed in IgAN patients with hyperuricemia compared without hyperuricemia group. Additionally, the estimated glomerular filtration rate (p < 0.00001, MD = - 29.03, 95% CI - 36.83 to - 21.23) was decreased in IgAN patients with hyperuricemia compared with normouricemic group. CONCLUSION: Hyperuricemia exacerbates IgAN prognosis through aggravating the clinical outcomes and pathological results of IgAN.
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Glomerulonefritis por IGA , Hiperuricemia , Creatinina , Tasa de Filtración Glomerular , Glomerulonefritis por IGA/patología , Humanos , Hiperuricemia/complicaciones , Pronóstico , Estudios RetrospectivosRESUMEN
Introduction: Acute pain is a prevalent problem for dementia residents in nursing homes. A variety of intervention strategies have been applied to address this problem. However, there remains an issue of inadequate pain control. This study aims to explore the analgesic efficacy of auricular acupressure (AA) for dementia residents with acute pain in nursing homes. Methods: A multicenter, single-blind, randomized, and sham-controlled clinical trial was performed in three nursing homes in Yinchuan, China. All of the 206 eligible patients with acute pain were randomly divided into two groups for real AA therapy or sham AA (at sham point stimulation) therapy. The primary outcome was measured with a face pain scale revised (FPS-R) score before the procedure, 5 min after the start of the intervention, and 5 min after finishing the procedure. Secondary outcomes covered three physiological parameters, adverse reactions observed, satisfaction level of caregivers, acceptance of patients, and additional use of analgesics. Results: There was a significant difference in pain scores based on FPS-R between the two groups (p < 0.01). Pain score in the true AA group was 1.84 ± 0.23, compared with 2.22 ± 0.81 in the sham AA group. No adverse events were found during the whole procedure for all patients. The satisfaction level of caregivers and acceptance of patients in the real AA group were significantly higher than those in the sham AA group. Conclusion: This study shows that real AA was an alternative analgesic modality in reducing acute pain in patients with mild dementia.
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Hydrogen evolution reaction (HER) has a dominant function in energy conversion and storage because it supplies a most effective way for converting electricity into sustainable high-purity hydrogen. Layered double hydroxides (LDHs) have shown promising performance in the process of electrochemical water oxidation (a half-reaction for water splitting). Nevertheless, HER properties have not been well released due to the structural characteristics of related materials. Herein, a simple and scalable tactics is developed to synthesize chromium-doped CoFe LDH (CoFeCr LDH). Thanks to oxygen vacancy, optimized electronic structure and interconnected array hierarchical structure, our developed ternary CoFeCr-based layered double hydroxide catalysts can provide 10 mA cm-2 current density at -0.201 V vs. RHE with superior long-term stability in alkaline electrolyte. We anticipate that the simple but feasible polymetallic electronic modulation strategy can strengthen the electrocatalytic property of the layered double hydroxides established in the present study, based on a carbon neutral and hydrogen economy.
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BACKGROUND: Common and frequent as acute pain is, it is often underestimated and undertreated in older people with dementia in nursing homes and inadequate pain management remains an issue. METHODS: The study is designed to be a randomized, sham-controlled trial and is underway in nursing homes located in China. A total of 206 dementia patients are being recruited from nursing homes in Yinchuan, China. They are randomly allocated to an intervention or a controlled group in a 1:1 ratio. The intervention group will be treated with true APP therapy, while the other group will receive APP at sham point stimulation therapy. The patients will be assessed at baseline (T0), at 5 min during performing the intervention (T1), and at 5 min after completion of the intervention (T2). The primary outcome is the level of pain relief at T1 and T2. Physiological parameters, side effects and additional use of analgesics during the procedure, satisfaction from caregivers, and acceptance of patients are evaluated as secondary outcomes. DISCUSSION: The results of this study are expected to verify the analgesic effect of APP for acute pain in patients with mild dementia in nursing homes. It has the potential to prompt APP therapy to be implemented widely in dementia patients with acute pain in nursing homes. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2100047932 . Registered on 27 June 2021. Currently, patient recruitment is ongoing. Recruitment is expected to take place from December 2020 to December 2021.
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Acupresión , Dolor Agudo , Demencia , Acupresión/métodos , Dolor Agudo/diagnóstico , Dolor Agudo/terapia , Anciano , Analgésicos/efectos adversos , Demencia/complicaciones , Demencia/diagnóstico , Demencia/terapia , Humanos , Ensayos Clínicos Controlados Aleatorios como Asunto , Resultado del TratamientoRESUMEN
NADPH oxidase-derived reactive oxygen species are involved in angiogenesis in vitro and regulated by ras-related C3 botulinum toxin substrate 1 (Rac1). This study has employed vector-based short hairpin RNA targeting Rac1 (Rac1-shRNA) to investigate the inhibitory effect on hypoxia-induced retinal neovascularization (RN) in vivo and the underlying mechanism. pSUPER-Rac1-shRNA was intravitreally injected into the mouse model of oxygen-induced retinopathy. RN was evaluated by FITC-dextran angiography and quantitated histologically. Expressions of Rac1, nuclear factor kappa B (NF-κB) subunit p65, hypoxia-inducible factor-1 alpha (HIF-1α), and vascular endothelial growth factor (VEGF) were determined by real-time quantitative RT-PCR and western blotting. After intravitreal administration of pSUPER-Rac1-shRNA, retinal Rac1 gene expression was reduced by 72% at postnatal day 17 (P17). Retinal flat mount and quantification of the neovascular nuclei demonstrated that RN was significantly inhibited. Meanwhile, the expression levels of NF-κB and HIF-1α, the redox-dependent transcription factors, were significantly downregulated. HIF-1α and its downstream gene VEGF were found to be significantly decreased at both transcriptional and translational levels. Our findings not only suggest that Rac1 may be involved in the process of RN in mouse oxygen-induced retinopathy via regulating the redox signaling, but may also provide a novel therapeutic target for hypoxia-induced retinal neovascular diseases.
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Modelos Animales de Enfermedad , Hipoxia/complicaciones , Neuropéptidos/genética , ARN Interferente Pequeño/farmacología , Neovascularización Retiniana/prevención & control , Transducción de Señal/efectos de los fármacos , Proteínas de Unión al GTP rac/genética , Animales , Animales Recién Nacidos , Western Blotting , Dextranos , Angiografía con Fluoresceína , Fluoresceína-5-Isotiocianato/análogos & derivados , Expresión Génica , Células HeLa , Humanos , Subunidad alfa del Factor 1 Inducible por Hipoxia/genética , Inyecciones Intravítreas , Ratones , Ratones Endogámicos C57BL , Oxidación-Reducción , Oxígeno/toxicidad , Interferencia de ARN , Neovascularización Retiniana/etiología , Neovascularización Retiniana/genética , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Factor de Transcripción ReIA/genética , Transfección , Factor A de Crecimiento Endotelial Vascular/genética , Proteína de Unión al GTP rac1RESUMEN
BACKGROUND: The pathological characteristics of IgA nephropathy (IgAN) are highly variable. Urinary kidney injury molecule-1 (KIM-1) is a sensitive biomarker for proximal tubule injury. The aim of the study is to investigate the value of KIM-1 as a biomarker for assessing the renal injury in IgAN. METHODS: The levels of urinary KIM-1 in 202 patients with IgAN, 46 patients with other renal diseases as disease controls and 60 healthy blood donors as normal controls were measured. Correlations with clinical and histopathological features of patients with IgAN were evaluated. RESULTS: The levels of urinary KIM-1 were significantly higher in patients with IgAN than in normal controls (P < 0.001) and in patients with non-IgAN (P = 0.011). Urinary levels of KIM-1 in IgAN positively correlated with levels of serum creatinine and proteinuria and negatively with creatinine clearance. The more severe the tubulointerstitial injury was, the higher the levels of urinary KIM-1. Patients with severe mesangial proliferation, crescents formation or endocapillary proliferation had higher levels of urinary KIM-1 than those without. The levels of tubular KIM-1 expression in immunohistochemistry closely correlated with the levels of urinary KIM-1 (r = 0.553, P = 0.032). Renal survival was significantly worse in patients with elevated urinary KIM-1 (P = 0.020). CONCLUSION: Urinary KIM-1 may be a useful biomarker to evaluate kidney injury in IgAN.
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Biomarcadores/orina , Glomerulonefritis por IGA/complicaciones , Necrosis Tubular Aguda/orina , Glicoproteínas de Membrana/orina , Nefritis Intersticial/orina , Adulto , Estudios de Casos y Controles , Creatinina/sangre , Femenino , Glomerulonefritis por IGA/mortalidad , Receptor Celular 1 del Virus de la Hepatitis A , Humanos , Pruebas de Función Renal , Necrosis Tubular Aguda/etiología , Necrosis Tubular Aguda/mortalidad , Masculino , Nefritis Intersticial/etiología , Nefritis Intersticial/mortalidad , Pronóstico , Proteinuria/mortalidad , Proteinuria/patología , Proteinuria/orina , Receptores Virales , Tasa de SupervivenciaRESUMEN
The ability to detect and remove dead adult bees is an essential part of honeybee colony fitness that prevents the spread of pathogens. Fatty acid olfactory cues stimulate undertaking behavior among different social species within Hymenoptera, but the chemicals responsible for the death cue in Apis cerana have not yet been identified. We explored the Nasonov gland as a potential source of these chemicals in A. cerana. Gas chromatography indicated that unlike A. mellifera, the A. cerana Nasonov gland does not contain any volatile terpenes, only fatty acids. As a bioassay, dead honeybees were rinsed free of their individual cuticular hydrocarbons via dichloromethane and two concentrations of oleic acid and a synthetic blend of the Nasonov pheromone in A. cerana were applied to the dummies. Results showed that oleic acid did not stimulate corpse removal in A. cerana. However, the synthetic pheromone blend of A. cerana Nasonov did stimulate removal.
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Abejas/química , Muerte , Feromonas/química , Animales , Conducta Animal , Señales (Psicología)RESUMEN
The water oxidation reaction plays a major role in many alternative-energy systems because it provides the electrons and protons required for the use of renewable electricity. We report the tuning of the iron molybdate (FeMoO4) electron structure via a coupled interface between the catalytic centers and the substrate. Our developed FeMoO4 catalysts can provide a 50 mA cm-2 current density at 1.506 V vs. RHE with excellent stability in 1.0 M KOH. The improved performance can be ascribed to the synergy of the optimized electronic structures and hierarchical nanostructure.
RESUMEN
The activation of C-H bonds is a central challenge in organic chemistry and usually a key step for the retro-synthesis of functional natural products due to the high chemical stability of C-H bonds. Electrochemical methods are a powerful alternative for C-H activation, but this approach usually requires high overpotential and homogeneous mediators. Here, we design electron-deficient W2C nanocrystal-based electrodes to boost the heterogeneous activation of C-H bonds under mild conditions via an additive-free, purely heterogeneous electrocatalytic strategy. The electron density of W2C nanocrystals is tuned by constructing Schottky heterojunctions with nitrogen-doped carbon support to facilitate the preadsorption and activation of benzylic C-H bonds of ethylbenzene on the W2C surface, enabling a high turnover frequency (18.8 h-1) at a comparably low work potential (2 V versus SCE). The pronounced electron deficiency of the W2C nanocatalysts substantially facilitates the direct deprotonation process to ensure electrode durability without self-oxidation. The efficient oxidation process also boosts the balancing hydrogen production from as-formed protons on the cathode by a factor of 10 compared to an inert reference electrode. The whole process meets the requirements of atomic economy and electric energy utilization in terms of sustainable chemical synthesis.