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Fast radio bursts (FRBs) are millisecond-duration radio transients1,2 of unknown origin. Two possible mechanisms that could generate extremely coherent emission from FRBs invoke neutron star magnetospheres3-5 or relativistic shocks far from the central energy source6-8. Detailed polarization observations may help us to understand the emission mechanism. However, the available FRB polarization data have been perplexing, because they show a host of polarimetric properties, including either a constant polarization angle during each burst for some repeaters9,10 or variable polarization angles in some other apparently one-off events11,12. Here we report observations of 15 bursts from FRB 180301 and find various polarization angle swings in seven of them. The diversity of the polarization angle features of these bursts is consistent with a magnetospheric origin of the radio emission, and disfavours the radiation models invoking relativistic shocks.
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BACKGROUND: Immune checkpoint inhibitors in combination with tyrosine kinase inhibitors are standard treatments for advanced clear cell renal cell carcinoma (RCC). This phase III RENOTORCH study compared the efficacy and safety of toripalimab plus axitinib versus sunitinib for the first-line treatment of patients with intermediate-/poor-risk advanced RCC. PATIENTS AND METHODS: Patients with intermediate-/poor-risk unresectable or metastatic RCC were randomized in a ratio of 1 : 1 to receive toripalimab (240 mg intravenously once every 3 weeks) plus axitinib (5 mg orally twice daily) or sunitinib [50 mg orally once daily for 4 weeks (6-week cycle) or 2 weeks (3-week cycle)]. The primary endpoint was progression-free survival (PFS) assessed by an independent review committee (IRC). The secondary endpoints were investigator-assessed PFS, overall response rate (ORR), overall survival (OS), and safety. RESULTS: A total of 421 patients were randomized to receive toripalimab plus axitinib (n = 210) or sunitinib (n = 211). With a median follow-up of 14.6 months, toripalimab plus axitinib significantly reduced the risk of disease progression or death by 35% compared with sunitinib as assessed by an IRC [hazard ratio (HR) 0.65, 95% confidence interval (CI) 0.49-0.86; P = 0.0028]. The median PFS was 18.0 months in the toripalimab-axitinib group, whereas it was 9.8 months in the sunitinib group. The IRC-assessed ORR was significantly higher in the toripalimab-axitinib group compared with the sunitinib group (56.7% versus 30.8%; P < 0.0001). An OS trend favoring toripalimab plus axitinib was also observed (HR 0.61, 95% CI 0.40-0.92). Treatment-related grade ≥3 adverse events occurred in 61.5% of patients in the toripalimab-axitinib group and 58.6% of patients in the sunitinib group. CONCLUSION: In patients with previously untreated intermediate-/poor-risk advanced RCC, toripalimab plus axitinib provided significantly longer PFS and higher ORR than sunitinib and had a manageable safety profile TRIAL REGISTRATION: ClinicalTrials.gov NCT04394975.
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Anticuerpos Monoclonales Humanizados , Carcinoma de Células Renales , Neoplasias Renales , Humanos , Anticuerpos Monoclonales Humanizados/uso terapéutico , Axitinib/uso terapéutico , Carcinoma de Células Renales/tratamiento farmacológico , Carcinoma de Células Renales/patología , Neoplasias Renales/tratamiento farmacológico , Sunitinib/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversosRESUMEN
We investigate how altering the interface geometry from a zigzag to a glide plane interface between two topologically distinct valley Hall emulating photonic crystals (VPC), profoundly affects edge states. We experimentally observe a transition from gapless to gapped edge states, accompanied by the occurrence of slow light within the Brillouin zone, rather than at its edge. We numerically simulate the propagation and measure the transmittance of the modified edge states through a specially designed valley-conserving defect. The robustness to backscattering gradually decreases, suggesting a disruption of valley-dependent transport. We demonstrate the significance of interface geometry to gapless edge states in a VPC.
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OBJECTIVE: To investigate the correlation between bone metabolism markers, bone mineral density (BMD), and sarcopenia. METHODS: A total of 331 consecutive patients aged ≥ 60 years who were hospitalized between November 2020 and December 2021 were enrolled. Participants were divided into sarcopenia and non-sarcopenia groups according to the Asian Working Group on Sarcopenia criteria (AWGS, 2019). The clinical data, bone metabolism markers (ß-CTX, N-MID, and TP1NP), and BMD were compared between the two groups. RESULTS: Age, ß-CTX, and N-MID of the sarcopenia group were higher than those of the non-sarcopenia group (P < 0.05), but the BMD T values were lower than those of the non-sarcopenia group (P < 0.05). Binary logistic regression analysis showed that increased femoral neck BMD (FNBMD) was a protective factor for sarcopenia, while increased ß-CTX was a risk factor. Pearson/Spearman correlation analysis showed that the diagnostic indices of sarcopenia were positively correlated with FNBMD and negatively correlated with ß-CTX and N-MID. Multiple linear regression analysis revealed that BMI and FNBMD significantly positively affected muscle strength and appendicular skeletal muscle mass (ASM). The FNBMD significantly positively affected physical performance, while ß-CTX significantly negatively affected muscle strength, ASM, and physical performance. CONCLUSION: Increased FNBMD may be a protective factor against sarcopenia, and increased ß-CTX may be a risk factor. The FNBMD significantly positively affected the diagnostic indices of sarcopenia, while ß-CTX significantly negatively affected them. BMD and bone metabolism marker levels may be considered in early screening for sarcopenia.
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Biomarcadores , Densidad Ósea , Sarcopenia , Humanos , Sarcopenia/diagnóstico , Sarcopenia/metabolismo , Femenino , Masculino , Densidad Ósea/fisiología , Anciano , Biomarcadores/análisis , Persona de Mediana Edad , Procolágeno/sangre , Músculo Esquelético/metabolismo , Fragmentos de Péptidos/sangre , Colágeno Tipo I/sangre , Huesos/metabolismo , Fuerza Muscular/fisiologíaRESUMEN
BACKGROUND: Microsurgical training should be implemented with consideration of operative difficulties that occur in actual clinical situations. We evaluated the effectiveness of a novel clinical scenario simulator for step-by-step microsurgical training that progressed from conventional training to escalated training with additional obstacles. METHODS: A training device was designed according to multiple and intricate clinical microsurgery scenarios. Twenty surgical residents with no experience in microsurgery were randomly assigned to either the control group (conventional training curricula, n = 10) or the experimental group (step-by-step training courses, n = 10). After 4 weeks of laboratory practice, the participants were scheduled to perform their first microvascular anastomoses on patients in an operating room. The Global Rating Scale (GRS) scores and operative duration were used to compare microsurgical skills between the two groups. RESULTS: There were no significant differences in the participants' baseline characteristics before microsurgical training between the groups with respect to age, sex, postgraduate year, surgical specialty, or mean GRS score (p < 0.05). There were also no significant differences in recipient sites between the two groups (p = 0.735). After training, the GRS scores in both groups were significantly improved (p = 0.000). However, in the actual microsurgical situations, the GRS scores were significantly higher in the experimental than control group (p < 0.05). There was no significant difference in the operative duration between the two groups (p < 0.13). CONCLUSION: Compared with a traditional training program, this step-by-step microsurgical curriculum based on our clinical scenario simulator results in significant improvement in acquisition of microsurgical skills.
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Competencia Clínica , Internado y Residencia , Microcirugia , Entrenamiento Simulado , Microcirugia/educación , Humanos , Entrenamiento Simulado/métodos , Masculino , Femenino , Adulto , Educación de Postgrado en Medicina/métodos , Curriculum , Tempo Operativo , Anastomosis Quirúrgica/educaciónRESUMEN
This study was to investigate the relationship between spring pollen distribution concentration, species and the detection results of air-borne pollen allergens in Taiyuan City, Shanxi Province during March to May 2022 and March to May 2023.A retrospective study was conducted in the Otorhinolaryngology Head and Neck Surgery Clinic of the First Hospital of Shanxi Medical University.Pollen particles will be monitored by gravity sedimentation method on the roof of the outpatient department of the First Hospital of Shanxi Medical University in downtown Taiyuan from March to May 2022-2023, and pollen species and quantity will be observed and recorded under an optical microscope.The air-borne pollen allergen detection results of all allergic rhinitis patients in the otolaryngology Head and Neck surgery Department of the First Hospital of Shanxi Medical University were extracted from the relevant outpatient system. SPSS software and Pearson correlation analysis were used to compare the correlation between the allergens and the dominant air-borne pollen monitoring results. Results are as follows: (1)A total of 18 species of spring pollen in Taiyuan City were monitored in 2022-2023, with 101 177.5 grains, and the dominant airborne pollen was poplar (16.69%) and pine (29.06%) pollen. The pollen of poplar (11.96%), elm (7.89%) and cypress (8.68%) were dominant in early spring; Pine (25.16%) pollen predominated in late spring. The two peaks of pollen dispersal in Taiyuan were in late March (15 479 grains) and early and mid May (15 094/15 343 grains).(2) The positive rates of allergens in serum specific IgE detection were: wormwood (46%, 248/541 cases), tree combination (26%, 143/541 cases), ragweed (19%, 101/541 cases), humulus scandens (9%, 49/541 cases).(3)There was a linear positive correlation between the positive rate of air-borne pollen allergens in allergic rhinitis patients in the Department of Otolaryngology Head and Neck Surgery in the First Hospital of Shanxi Medical University and the dominant air-borne pollen concentration in the same period (P<0.05, r=0.999). In conclusion, two spring pollen dispersal peaks were formed in late March and early to mid May in Taiyuan City, and the dominant air-borne pollens were poplar and pine pollens. The positive rate of air borne pollen allergen sIgE showed that wormwood allergy was the highest.There was a positive correlation between the concentration of air-borne pollen and the positive rate of air-borne pollen allergens in patients with allergic rhinitis in the Department of otorhinolaryngology and head and neck surgery in Taiyuan in 2022 and 2023.The monitoring of pollen distribution in spring can provide an important scientific basis for clinical workers to formulate prevention and treatment plans for patients with allergic rhinitis in the season, and provide data reference for the epidemiological investigation of allergic diseases in Taiyuan in the future.
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Alérgenos , Polen , Humanos , China , Estudios Retrospectivos , Inmunoglobulina E/sangre , Estaciones del Año , Rinitis Alérgica , Rinitis Alérgica EstacionalRESUMEN
Objective: To understand the epidemiological characteristics of human respiratory syncytial virus (HRSV) among acute respiratory infection (ARI) cases in 16 provinces of China from 2009 to 2023. Methods: The data of this study were collected from the ARI surveillance data from 16 provinces in China from 2009 to 2023, with a total of 28 278 ARI cases included in the study. The clinical specimens from ARI cases were screened for HRSV nucleic acid from 2009 to 2023, and differences in virus detection rates among cases of different age groups, regions, and months were analyzed. Results: A total of 28 278 ARI cases were enrolled from January 2009 to September 2023. The age of the cases ranged from<1 month to 112 years, and the age M (Q1, Q3) was 3 years (1 year, 9 years). Among them, 3 062 cases were positive for HRSV nucleic acid, with a total detection rate of 10.83%. From 2009 to 2019, the detection rate of HRSV was 9.33%, and the virus was mainly prevalent in winter and spring. During the Corona Virus Disease 2019 (COVID-19) pandemic, the detection rate of HRSV fluctuated between 6.32% and 18.67%. There was no traditional winter epidemic peak of HRSV from the end of 2022 to the beginning of 2023, and an anti-seasonal epidemic of HRSV occurred from April to May 2023. About 87.95% (2 693/3 062) of positive cases were children under 5 years old, and the difference in the detection rate of HRSV among different age groups was statistically significant (P<0.001), showing a decreasing trend of HRSV detection rate with the increase of age (P<0.001). Among them, the HRSV detection rate (25.69%) was highest in children under 6 months. Compared with 2009-2019, the ranking of HRSV detection rates in different age groups changed from high to low between 2020 and 2023, with the age M (Q1, Q3) of HRSV positive cases increasing from 1 year (6 months, 3 years) to 2 years (11 months, 3 years). Conclusion: Through 15 years of continuous HRSV surveillance analysis, children under 5 years old, especially infants under 6 months old, are the main high-risk population for HRSV infection. During the COVID-19 pandemic, the prevalence and patterns of HRSV in China have changed.
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Infecciones por Virus Sincitial Respiratorio , Virus Sincitial Respiratorio Humano , Infecciones del Sistema Respiratorio , Humanos , China/epidemiología , Infecciones por Virus Sincitial Respiratorio/epidemiología , Virus Sincitial Respiratorio Humano/aislamiento & purificación , Infecciones del Sistema Respiratorio/epidemiología , Infecciones del Sistema Respiratorio/virología , Preescolar , Lactante , Niño , Adolescente , Adulto , Estaciones del Año , Masculino , Persona de Mediana Edad , Femenino , Anciano , Adulto Joven , COVID-19/epidemiología , Enfermedad Aguda , Anciano de 80 o más AñosRESUMEN
The cardiac perivascular niche is a cellular microenvironment of a blood vessel. The principles of niche regulation are still poorly understood. We studied the effect of TGFß1 on cells forming the cardiac perivascular niche using 3D cell culture (cardiospheres). Cardiospheres contained progenitor (c-Kit), endothelial (CD31), and mural (αSMA) cells, basement membrane proteins (laminin) and extracellular matrix proteins (collagen I, fibronectin). TGFß1 treatment decreased the length of CD31+ microvasculature, VE cadherin protein level, and proportion of NG2+ cells, and increased proportion of αSMA+ cells and transgelin/SM22α protein level. We supposed that this effect is related to the stabilizing function of TGFß1 on vascular cells: decreased endothelial cell proliferation, as shown for HUVEC, and activation of mural cell differentiation.
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Diferenciación Celular , Proliferación Celular , Factor de Crecimiento Transformador beta1 , Factor de Crecimiento Transformador beta1/farmacología , Factor de Crecimiento Transformador beta1/metabolismo , Diferenciación Celular/efectos de los fármacos , Humanos , Proliferación Celular/efectos de los fármacos , Células Endoteliales de la Vena Umbilical Humana/metabolismo , Células Endoteliales de la Vena Umbilical Humana/efectos de los fármacos , Animales , Proteínas de Microfilamentos/metabolismo , Proteínas de Microfilamentos/genética , Molécula-1 de Adhesión Celular Endotelial de Plaqueta/metabolismo , Cadherinas/metabolismo , Laminina/metabolismo , Laminina/farmacología , Proteínas Musculares/metabolismo , Células Cultivadas , Células Endoteliales/metabolismo , Células Endoteliales/efectos de los fármacos , Células Endoteliales/citología , Fibronectinas/metabolismo , Fibronectinas/farmacología , Antígenos CD/metabolismo , Miocardio/metabolismo , Miocardio/citología , Nicho de Células Madre/efectos de los fármacos , Nicho de Células Madre/fisiología , Colágeno Tipo I/metabolismo , Esferoides Celulares/efectos de los fármacos , Esferoides Celulares/metabolismo , Esferoides Celulares/citología , Técnicas de Cultivo Tridimensional de Células/métodosRESUMEN
The COVID-19 pandemic has brought significant changes in managing of patients with rheumatoid arthritis. Rituximab-treated patients were more susceptible to severe infection. This required a "switch" to another genetically engineered drug in the patients with high risk of adverse COVID-19. In this study, we assessed the severity of immune response to SARS-CoV-2 antigens in rituximab-treated patients with rheumatoid arthritis vaccinated with the combined vector vaccine Gam-COVID-Vac. Insufficient formation of the humoral response and a high level of T-cell response to SARS-CoV-2 antigens in this group of patients were revealed. An imbalance of cellular and humoral response may play a role in more severe COVID-19 in rituximab-treated patients with rheumatoid arthritis.
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Artritis Reumatoide , Vacunas contra la COVID-19 , COVID-19 , Inmunidad Humoral , Rituximab , SARS-CoV-2 , Artritis Reumatoide/inmunología , Artritis Reumatoide/tratamiento farmacológico , Humanos , Rituximab/uso terapéutico , Inmunidad Humoral/efectos de los fármacos , SARS-CoV-2/inmunología , COVID-19/inmunología , COVID-19/prevención & control , Persona de Mediana Edad , Masculino , Femenino , Vacunas contra la COVID-19/inmunología , Linfocitos T/inmunología , Linfocitos T/efectos de los fármacos , Anciano , Anticuerpos Antivirales/inmunología , Anticuerpos Antivirales/sangre , Adulto , Antirreumáticos/uso terapéutico , VacunaciónRESUMEN
Following the global outbreak of COVID-19, many patients have suffered from multi-system complications and long-term sequelae caused by the virus. Diaphragm dysfunction is an obscure post-COVID-19 symptom. Although a few cases of diaphragm dysfunction caused by COVID-19 infection have been reported abroad, there are no relevant reports in China. Herein, we present two cases of patients with respiratory distress after COVID-19 infection. On admission, dynamic chest radiographs revealed diaphragm dysfunction in these patients. Further investigations including diaphragm ultrasound, neurophysiological examinations, transdiaphragmatic pressure measurements cranial MRI, and antibody testing for autoimmune diseases, were conducted. The final diagnoses were severe myasthenia gravis induced by COVID-19 infection and diaphragmatic nerve and muscle involvement caused by COVID-19 infection. Both patients showed improvement in symptoms after treatment. Therefore, we summarized our case, with a review of the relevant literature to improve the understanding of the disease and to provide clinical evidence for future diagnosis and treatment.
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Enfermedades Autoinmunes , COVID-19 , Humanos , Diafragma , Tórax , ChinaRESUMEN
Objective: To investigate the effects of zinc oxide nanoparticles (ZnO-NPs) on neutrophil hypoxia and pyroptosis through nucleotide binding of oligomeric domain-like receptor protein 3 (NLRP3) inflammasome, and to analyze the role of pyroptosis on respiratory tract inflammotion induced by ZnO-NPs. Methods: In October 2022, primary cultured neutrophils were obtained from the abdominal aortic blood of SPF adult healthy SD rats. The neutrophils were treated with ZnO-NPs solution (0, 5, 10, 20 µg/ml) at different concentrations, and hypoxia group (5% O(2)) was set up. Hypoxia and reactive oxygen species (ROS) levels were detected by flow cytometry, and the expression levels of NLRP3, apoptosis-associated speck-like protein containing a CARD (ASC), cleaved Caspase-1 were measured by Western blot. The activity of lactic dehydrogenase (LDH) in the cell supernatant was measured by coloration, and the content of interleukin-1 beta (IL-1ß) in cell culture supernatant was detected by enzyme-linked immunosorbent assay (ELISA) . Results: Compared with the control group, hypoxia and ROS levels of neutrophils in hypoxia group and ZnO-NPs groups were significantly increased (P<0.05), and NLRP3, ASC, cleaved Caspase-1 protein expression levels, LDH activity and IL-1ß content were significantly increased (P<0.05). Compared with hypoxia group, hypoxia and ROS levels of neutrophils in 5 µg/ml and 10 µg/ml ZnO-NPs groups were significantly decreased (P<0.05), NLRP3, ASC, cleaved Caspase-1 protein expression levels, LDH activity, and IL-1ß content were decreased significantly (P<0.05). There were no significant differences in hypoxia, ROS levels, ASC, cleaved Caspase-1 protein expression levels, LDH activity, and IL-1ß content between the 20 µg/ml ZnO-NPs group and the hypoxia group (P>0.05) . Conclusion: ZnO-NPs treatment may activate the NLRP3 inflammasome to induce pyroptosis of neutrophils which may be related to ROS and hypoxia.
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Caspasa 1 , Proteína con Dominio Pirina 3 de la Familia NLR , Nanopartículas , Neutrófilos , Piroptosis , Ratas Sprague-Dawley , Especies Reactivas de Oxígeno , Óxido de Zinc , Animales , Piroptosis/efectos de los fármacos , Ratas , Neutrófilos/efectos de los fármacos , Neutrófilos/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Caspasa 1/metabolismo , Interleucina-1beta/metabolismo , Inflamasomas/metabolismo , Inflamasomas/efectos de los fármacos , Células Cultivadas , Masculino , Hipoxia/metabolismo , Hipoxia de la CélulaRESUMEN
OBJECTIVE: To improve the outcomes in patients with malignant obstructive jaundice using intraluminal stenting. MATERIAL AND METHODS: The present study included 62 patients with clinical symptoms of malignant obstructive jaundice. In the main group, we performed biliary stenting with self-expanding multi-perforated stents (Hanarostent Multi-hole Biliary). Microscopic perforations of these stents prevent migration and reduce the risk of blocking the cystic and main pancreatic ducts. In the control group, stenting was performed with fully and partially covered self-expanding stents. RESULTS: Lower incidence of obstructive cholecystitis and acute pancreatitis in the main group was associated with multiperforated stents reducing the risk of blocking the main pancreatic and cystic ducts. CONCLUSION: In our study, multiperforated stents excluded migration and reduced the incidence of complications (acute cholecystitis from 11.5 to 3.8%, acute pancreatitis from 15.3 to 7.7%).
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Ictericia Obstructiva , Pancreatitis , Humanos , Enfermedad Aguda , Constricción Patológica , Ictericia Obstructiva/diagnóstico , Ictericia Obstructiva/etiología , Ictericia Obstructiva/cirugía , Pancreatitis/complicaciones , Pancreatitis/diagnóstico , Stents/efectos adversosRESUMEN
The introduction of early diagnostic methods for keratoconus into clinical practice has become the basis for the development of surgical treatment techniques for this pathology, such as corneal collagen crosslinking and interlamellar keratoplasty with implantation of intrastromal segments. The article analyzes the results of research by Russian and foreign specialists in these areas and presents the data on the combination of SMILE surgery and corneal crosslinking, the Rome protocol of corneal crosslinking, modifications of interlamellar keratoplasty, the use of femtosecond laser technologies, and some pilot studies. Modern requirements for ophthalmological care require a personalized approach to each patient, and therefore the surgeon should have a wide range of surgical methods of treatment applicable to different patient cohorts. The described methods of treatment, according to the authors, are the most promising.
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Queratocono , Queratocono/cirugía , Queratocono/diagnóstico , Humanos , Córnea/cirugía , Córnea/diagnóstico por imagen , Trasplante de Córnea/métodos , Cirugía Laser de Córnea/métodos , Resultado del Tratamiento , ColágenoRESUMEN
Bempegaldesleukin (BEMPEG), a CD122-preferential IL2 pathway agonist, has been shown to induce proliferation and activation of NK cells. NK activation is dependent on the balance of inhibitory and excitatory signals transmitted by NK receptors, including Fc-gamma receptors (FCγRs) and killer immunoglobulin-like receptors (KIRs) along with their KIR-ligands. The repertoire of KIRs/KIR-ligands an individual inherits and the single-nucleotide polymorphisms (SNPs) of FCγRs can influence NK function and affect responses to immunotherapies. In this retrospective analysis of the single-arm PIVOT-02 trial, 200 patients with advanced solid tumors were genotyped for KIR/KIR-ligand gene status and FCγR SNP status and evaluated for associations with clinical outcome. Patients with inhibitory KIR2DL2 and its ligand (HLA-C1) observed significantly greater tumor shrinkage (TS, median change -13.0 vs. 0%) and increased PFS (5.5 vs. 3.3 months) and a trend toward improved OR (31.2 vs. 19.5%) compared to patients with the complementary genotype. Furthermore, patients with KIR2DL2 and its ligand together with inhibitory KIR3DL1 and its ligand (HLA-Bw4) had improved OR (36.5 vs. 19.6%), greater TS (median change -16.1 vs. 0%), and a trend toward prolonged PFS (8.4 vs. 3.6 months) as compared to patients with the complementary genotype. FCγR polymorphisms did not influence OR/PFS/TS.These data show that clinical response to BEMPEG plus nivolumab treatment in the PIVOT-02 trial may be associated with the repertoire of KIR/KIR-ligands an individual inherits. Further investigation and validation of these results may enable KIR/KIR-ligand genotyping to be utilized prospectively for identifying patients likely to benefit from certain cancer immunotherapy regimens.
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Neoplasias , Nivolumab , Humanos , Nivolumab/uso terapéutico , Ligandos , Estudios Retrospectivos , Receptores de IgG/genética , Receptores KIR/genética , Receptores KIR/metabolismo , Genotipo , Polimorfismo de Nucleótido Simple , Neoplasias/tratamiento farmacológico , Neoplasias/genéticaRESUMEN
Low molecular-weight thiols as glutathione and cysteine are an important part of the cell's redox regulation system. Previously, we have shown that inactivation of ADP-heptose synthesis in Escherichia coli with a gmhA deletion induces the oxidative stress. It is accompanied by rearrangement of thiol homeostasis and increased sensitivity to antibiotics. In our study, we found that restriction of cysteine metabolism (ΔcysB and ΔcysE) and inhibition of glutathione synthesis (ΔgshAB) lead to a decrease in the sensitivity of the ΔgmhA mutant to antibiotics but not to its expected increase. At the same time, blocking of the export of cysteine (ΔeamA) or increasing import (Ptet-tcyP) into cells of the oxidized form of cysteine-cystine leads to an even greater increase in the sensitivity of gmhA-deleted cells to antibiotics. In addition, there is no correlation between the cytotoxic effect of antibiotics and the level of reactive oxygen species (ROS), the total pool of thiols, or the viability of the initial cell population. However, a correlation between the sensitivity to antibiotics and the level of oxidized glutathione in cells was found in our study. Apparently, a decrease in the content of low-molecular-weight thiols saves NADPH equivalents and limits the processes of protein redox modification. This leads to increasing of resistance of the ΔgmhA strain to antibiotics. An increase in low-molecular-weight thiols levels requires a greater expenditure of cell resources, leads to an increase in oxidized glutathione and induces to greater increase in sensitivity of the ΔgmhA strain to antibiotics.
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Cisteína , Compuestos de Sulfhidrilo , Compuestos de Sulfhidrilo/química , Compuestos de Sulfhidrilo/metabolismo , Cisteína/genética , Cisteína/metabolismo , Disulfuro de Glutatión/metabolismo , Escherichia coli/genética , Escherichia coli/metabolismo , Antibacterianos/farmacología , Glutatión/química , Glutatión/metabolismo , Oxidación-ReducciónRESUMEN
Metabolic stress caused by a lack of glucose significantly affects the state of red blood cells, where glycolysis is the main pathway for the production of ATP. Hypoglycemia can be both physiological (occurring during fasting and heavy physical exertion) and pathological (accompanying a number of diseases, such as diabetes mellitus). In this study, we have characterized the state of isolated erythrocytes under metabolic stress caused by the absence of glucose. It was established that 24 h of incubation of the erythrocytes in a glucose-free medium to simulate blood plasma led to a two-fold decrease in the ATP level into them. The cell size, as well as intracellular sodium concentration increased. These findings could be the result of a disruption in ion transporter functioning because of a decrease in the ATP level. The calcium level remained unchanged. With a lack of glucose in the medium of isolated erythrocytes, there was no increase in ROS and a significant change in the level of nitric oxide, while the level of the main low-molecular weight thiol of cells, glutathione (GSH) decreased by almost 2 times. It was found that the metabolic stress of isolated red blood cells induced hemoglobin glutathionylation despite the absence of ROS growth. The cause was the lack of ATP, which led to a decrease in the level of GSH because of the inhibition of its synthesis and, probably, due to a decrease in the NADPH level required for glutathione (GSSG) reduction and protein deglutathionylation. Thus, erythrocyte metabolic stress induced hemoglobin glutathionylation, which is not associated with an increase in ROS. This may have an important physiological significance, since glutathionylation of hemoglobin changes its affinity for oxygen.
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Glutatión , Hemoglobinas , Disulfuro de Glutatión/análisis , Disulfuro de Glutatión/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Oxidación-Reducción , Glutatión/análisis , Glutatión/metabolismo , Hemoglobinas/análisis , Hemoglobinas/metabolismo , Eritrocitos/química , Eritrocitos/metabolismo , Estrés Oxidativo , Glucosa/análisis , Glucosa/metabolismo , Adenosina TrifosfatoRESUMEN
Objective: To investigate the clinical and biological characteristics of familial platelet disorder (FPD) with germline Runt-related transcription factor (RUNX) 1 mutations. Methods: Patients diagnosed with myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML) with RUNX1 mutations from February 2016 to December 2021 in Wuhan No.1 Hospital underwent pedigree analysis and were screened for gene mutations (somatic and germline). Patients diagnosed with FPD with germline RUNX1 mutations were enrolled and evaluated in terms of clinical characteristics and biological evolution. Bioinformatics analysis was used to assess the pathogenicity of mutations and to analyze the effect of mutated genes on the function of the corresponding protein. Results: Germline RUNX1 mutations were detected in three out of 34 patients suffering from MDS/AML who had RUNX1 mutations. A pedigree of FPD with RUNX1 (RUNX1-FPD) c.562A>C and RUNX1 c.1415T>C mutations was diagnosed, and the mutations were of patrilineal origin. Bioinformatics analysis indicated that the locus at positions 188 and 472 in the AML-1G type of RUNX1 was highly conserved across different species, and that variations might influence functions of the proteins. The mutations were evaluated to be highly pathogenic. Of the nine cases with germline RUNX1 mutations: two patients died due AML progression; one case with AML survived without leukemia after transplantation of hemopoietic stem cells; four patients showed mild-to-moderate thrombocytopenia; two cases had no thrombocytopenia. During the disease course of the proband and her son, mutations in RUNX1, NRAS and/or CEBPA and KIT appeared in succession, and expression of cluster of differentiation-7 on tumor cells was enhanced gradually. None of the gene mutations correlated with the tumor were detected in the four cases not suffering from MDS/AML, and they survived until the end of follow-up. Conclusions: RUNX1-FPD was rare. The mutations c.562A>C and c.1415T>C of RUNX1 could be the disease-causing genes for the family with RUNX1-FPD, and these mutations could promote malignant transformation. Biological monitoring should be carried out regularly to aid early intervention for family members with RUNX1-FPD.
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Trastornos de las Plaquetas Sanguíneas , Leucemia Mieloide Aguda , Humanos , Femenino , Mutación de Línea Germinal , Subunidad alfa 2 del Factor de Unión al Sitio Principal/genética , Linaje , Trastornos de las Plaquetas Sanguíneas/genética , Trastornos de las Plaquetas Sanguíneas/complicaciones , Leucemia Mieloide Aguda/genéticaRESUMEN
Objectives: To investigated the safety and efficacy of treating patients with acute non-ST-segment elevation myocardial infarction (NSTEMI) and elevated levels of N-terminal pro-hormone B-type natriuretic peptide (NT-proBNP) with levosimendan within 24 hours of first medical contact (FMC). Methods: This multicenter, open-label, block-randomized controlled trial (NCT03189901) investigated the safety and efficacy of levosimendan as an early management strategy of acute heart failure (EMS-AHF) for patients with NSTEMI and high NT-proBNP levels. This study included 255 patients with NSTEMI and elevated NT-proBNP levels, including 142 males and 113 females with a median age of 65 (58-70) years, and were admitted in the emergency or outpatient departments at 14 medical centers in China between October 2017 and October 2021. The patients were randomly divided into a levosimendan group (n=129) and a control group (n=126). The primary outcome measure was NT-proBNP levels on day 3 of treatment and changes in the NT-proBNP levels from baseline on day 5 after randomization. The secondary outcome measures included the proportion of patients with more than 30% reduction in NT-proBNP levels from baseline, major adverse cardiovascular events (MACE) during hospitalization and at 6 months after hospitalization, safety during the treatment, and health economics indices. The measurement data parameters between groups were compared using the t-test or the non-parametric test. The count data parameters were compared between groups using the χ² test. Results: On day 3, the NT-proBNP levels in the levosimendan group were lower than the control group but were statistically insignificant [866 (455, 1 960) vs. 1 118 (459, 2 417) ng/L, Z=-1.25,P=0.21]. However, on day 5, changes in the NT-proBNP levels from baseline in the levosimendan group were significantly higher than the control group [67.6% (33.8%,82.5%)vs.54.8% (7.3%,77.9%), Z=-2.14, P=0.03]. There were no significant differences in the proportion of patients with more than 30% reduction in the NT-proBNP levels on day 5 between the levosimendan and the control groups [77.5% (100/129) vs. 69.0% (87/126), χ²=2.34, P=0.13]. Furthermore, incidences of MACE did not show any significant differences between the two groups during hospitalization [4.7% (6/129) vs. 7.1% (9/126), χ²=0.72, P=0.40] and at 6 months [14.7% (19/129) vs. 12.7% (16/126), χ²=0.22, P=0.64]. Four cardiac deaths were reported in the control group during hospitalization [0 (0/129) vs. 3.2% (4/126), P=0.06]. However, 6-month survival rates were comparable between the two groups (log-rank test, P=0.18). Moreover, adverse events or serious adverse events such as shock, ventricular fibrillation, and ventricular tachycardia were not reported in both the groups during levosimendan treatment (days 0-1). The total cost of hospitalization [34 591.00(15 527.46,59 324.80) vs. 37 144.65(16 066.90,63 919.00)yuan, Z=-0.26, P=0.80] and the total length of hospitalization [9 (8, 12) vs. 10 (7, 13) days, Z=0.72, P=0.72] were lower for patients in the levosimendan group compared to those in the control group, but did not show statistically significant differences. Conclusions: Early administration of levosimendan reduced NT-proBNP levels in NSTEMI patients with elevated NT-proBNP and did not increase the total cost and length of hospitalization, but did not significantly improve MACE during hospitalization or at 6 months.
Asunto(s)
Insuficiencia Cardíaca , Infarto del Miocardio sin Elevación del ST , Masculino , Femenino , Humanos , Anciano , Péptido Natriurético Encefálico , Simendán/uso terapéutico , Insuficiencia Cardíaca/tratamiento farmacológico , Fragmentos de Péptidos , Arritmias Cardíacas , Biomarcadores , PronósticoRESUMEN
Objective: To analyze the characteristics of human papillomavirus (HPV) infection and the distribution of HPV subtypes in Shijiazhuang, Hebei Province, and to explore the application evaluation of multiple PCR capillary electrophoresis fragment analysis for HPV typing test. Methods: A population-based cross-sectional study was conducted among 434 women (age range 17 to 74 years old, 260 patients and 174 physical examinations) included from May to August 2022 in Hebei General Hospital. HPV typing was detected by multiple PCR-capillary electrophoresis fragment analysis. Using the multiple fluorescence quantitative PCR kit as a reference, Chi-square test was used to analyze the diagnostic effect of multiple PCR-capillary electrophoresis fragment analysis, and the consistency was analyzed by Kappa value. Results: The total HPV infection rate was 45.85%(199/434), including 35.48% (154/434) of high-risk HPV (HR-HPV), 3.92% (17/434) of low-risk HPV (LR-HPV), 6.45% (28/434) of HR-HPV and LR-HPV mixed infection, 27.88% (121/434) of single type HPV and 17.97% (78/434) of multi type HPV. HPV52 (9.68%, 42/434), HPV16 (6.91%, 30/434), and HPV58 (6.91%, 30/434) are common HPV subtypes. The positive rate of physical examination was 45.40% (79/174), which was slightly lower than that of patients 46.15% (120/260), there was no significant difference (χ2=0.024,P>0.05). The highest infection rate in the 17-30 age group was 54.76% (46/84), and there was no statistical difference among the age groups(χ2=4.123,P>0.05). The sensitivity and specificity of multiplex PCR capillary electrophoresis fragment analysis were 92.96% and 94.04%, respectively, and Kappa value was 0.870, with the multiplex fluorescent quantitative PCR as the reference. Conclusion: HPV infection may appear younger, and the positive rate of HR-HPV infection is the highest, with HPV52, 16, 58 as the main infection subtypes. The detection results of multiplex PCR capillary electrophoresis fragment analysis method are highly consistent with those of multiplex fluorescent quantitative PCR method, which is suitable for HPV DNA typing.
Asunto(s)
Infecciones por Papillomavirus , Neoplasias del Cuello Uterino , Humanos , Femenino , Adolescente , Adulto Joven , Adulto , Persona de Mediana Edad , Anciano , Reacción en Cadena de la Polimerasa Multiplex , Infecciones por Papillomavirus/diagnóstico , Estudios Transversales , Genotipo , Papillomaviridae/genéticaRESUMEN
To study the efficacy and compliance analysis of pollen allergen drops in the treatment of allergic rhinitis. The method of single-center controlled was used to analyze the dates' results. From July 2021 to September 2021, 80 patients with seasonal allergic rhinitis were referred to the clinic of otorhinolaryngology in First Hospital of Shanxi Medical University.40 patients received sublingual immunotherapy (SLIT group), and the other 40 patients received symptomatic drug treatment as the control group. The total rhinoconjunctivitis symptom score (TRSS), the visual analogue scale(VAS), total medication score (TMS) and combined scores of medication and rhinoconjunctivitis symptoms (CSMRS) of the patient before the start of the treatment and after the first year of the treatment were compared to assess the efficacy of sublingual immunotherapy of Artemisia pollen. Follow the shedding during the study, the safety of the drug and the causes for compliance analysis were analyzed and recorded. The results of comparison with TRSS, VAS, TMS and CSMRS in two groups in the period of pretherapy were as follows: TRSS(12.393±3.023, 12.450±3.029, t=-0.077, P=0.939), VAS(8.357±1.026, 8.400±0.982, t=-0.173, P=0.862), TMS(3.214±0.568, 3.175±0.501, t=0.301, P=0.764), CSMRS (5.286±0.680, 5.253±0.677, t=0.199, P=0.843), there was no significant difference (P>0.05); lower observed symptom scores were got in the post-treatment pollen peak SLIT group compared to the control group, TRSS(3.964±1.551, 7.750±2.169, t=-7.918, P<0.05), VAS(2.893±0.956, 5.175±1.481, t=-8.286, P<0.05), TMS (1.821±0.863, 3.175±0.501, t=-8.163, P<0.05), CSMRS (2.489±0.921, 4.468±0.601, t=-10.723, P<0.05), and the differences between the groups were statistically significant (P<0.05); the SLIT group significantly reduced all symptom scores at the first peak compared to the starting, TRSS(12.393±3.023, 3.964±1.551, t=20.576, P<0.05), VAS (8.357±1.026, 2.893±0.956, t=30.070, P<0.05), TMS (3.214±0.568, 1.821±0.863, t=7.151, P<0.05), CSMRS(5.286±0.680, 2.489±0.921, t=14.533, P<0.05) and there was statistical difference (P<0.05). No significant adverse reactions occured during medication in the SLIT group. A total of 12 cases were shed in the SLIT group, so the compliance rate was 70%. The four reasons were that patients considered the course was long (4 cases, 33%); the drugs were expensive (3 cases, 25%); patients were busy with their work and life (3 cases, 25%); patients were affected by the outbreak (2 cases, 17%). In summary, Artemisia pollen sublingual drops may improve the symptoms of the patients who got allergic rhinitis caused by Artemisia pollen after the treatment for one year. However, due to the lack of sufficient understanding of immunotherapy or the difficulty in adhering to standardized medication, the compliance with sublingual immunotherapy is still poor, the compliance with sublingual immunotherapy needs to be further improved through patient education.