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BACKGROUND: Folinic acid, fluorouracil, irinotecan, and oxaliplatin (FOLFIRINOX) or modified FOLFIRINOX (mFFX) is the first-line standard of care for metastatic pancreatic adenocarcinoma; effective and safe treatment strategies are needed as survival remains poor. Sintilimab, a human immunoglobulin G4 monoclonal antibody for programmed cell death-1, has shown efficacy in various cancers. We evaluated the efficacy and safety of sintilimab with mFFX for metastatic/recurrent pancreatic ductal adenocarcinoma in China. PATIENTS AND METHODS: This was a single-center, randomized, controlled, open-label phase II study. Patients were assigned 1:1 to sintilimab + mFFX or mFFX (n = 55, each). RESULTS: In the intention-to-treat population, median overall survivals (primary endpoint) were similar in the sintilimab + mFFX and mFFX groups: 10.9 and 10.8 months, respectively [hazard ratio (HR) 1.07, 95% confidence interval (CI) 0.69-1.68]. The objective response rate was higher [50.0% (95% CI 34.6-65.4%) versus 23.9% (95% CI 11.1-36.7%)] in the sintilimab + mFFX group (P < 0.05). Median (HR, 95% CI) progression-free survival and disease control rates (95% CI) were also similar at 5.9 and 5.7 months (0.93, 0.62-1.40), and 84.1% (72.8-95.3%) and 71.7%, (58.2-85.3%), respectively. Incidences of grade ≥ 3 treatment-emergent adverse events were 84.9% (45/53) and 74.1% (40/54), and that of grade ≥ 3 immune-related adverse events were 5.7% (3/53) and 0 in each group, respectively. CONCLUSIONS: The study did not meet its primary endpoint, no clear survival benefit was observed, and the benefit of sintilimab + mFFX for advanced pancreatic cancer was not supported; however, the findings suggest that using this regimen for pancreatic cancer is feasible, has an acceptable safety profile, and leads to an objective response rate of 50%. Trial registration ClinicalTrials.Gov; NCT03977272.
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Adenocarcinoma , Neoplasias Pancreáticas , Humanos , Neoplasias Pancreáticas/patología , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Recurrencia Local de Neoplasia/tratamiento farmacológico , Recurrencia Local de Neoplasia/etiología , Fluorouracilo/uso terapéutico , Leucovorina/uso terapéutico , Enfermedad Crónica , Neoplasias PancreáticasRESUMEN
BACKGROUND: With the advent of intensive combination regimens, an increasing number of patients with unresectable pancreatic cancer (UPC) have regained the opportunity for surgery. We investigated the clinical benefits and prognostic factors of conversion surgery (CS) in UPC patients. METHODS: We retrospectively enrolled patients with UPC who had received CS following first-line systemic treatment in our center between 2014 to 2022. Treatment response, safety of the surgical procedure and clinicopathological data were collected. We analyzed the prognostic factors for postoperative survival among UPC patients who had CS. RESULTS: Sixty-seven patients with UPC were enrolled (53 with locally advanced pancreatic cancer (LAPC) and 14 with metastatic pancreatic cancer (MPC)). The duration of preoperative systemic treatment was 4.17 months for LAPC patients and 6.52 months for MPC patients. All patients experienced a partial response (PR) or had stable disease (SD) preoperatively according to imaging. Tumor resection was unsuccessful in four patients and, finally, R0 resection was obtained in 81% of cases. Downstaging was determined pathologically in 87% of cases; four patients achieved a complete pathological response. Median postoperative-progression-free survival (PO-PFS) was 9.77 months and postoperative overall survival (PO-OS) was 31.2 months. Multivariate logistic regression analyses revealed that the resection margin and postoperative changes in levels of tumor markers were significant prognostic factors for PO-PFS. No factors were associated significantly with PO-OS according to multivariate analyses. CONCLUSIONS: CS is a promising strategy for improving the prognosis of UPC patients. The resection margin and postoperative change in levels of tumor markers are the most important prognostic factors for prolonged PFS. Multidisciplinary treatment in high-volume centers is strongly recommended. Prospective studies must be undertaken to resolve the various problems regarding optimal regimens, the duration of treatment, and detailed criteria for CS.
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Biomarcadores de Tumor , Neoplasias Pancreáticas , Humanos , Supervivencia sin Progresión , Estudios Prospectivos , Estudios Retrospectivos , Márgenes de Escisión , Neoplasias Pancreáticas/patología , Pronóstico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias PancreáticasRESUMEN
AIM: The aim of this study is to perform a Bayesian network meta-analysis to evaluate the safety and efficacy of prophylactic bolus of different doses of ephedrine, phenylephrine, and norepinephrine for the prevention of spinal hypotension during cesarean section. METHODS: The Web of Science, PubMed, EMBASE, Cochrane Library were searched until to May 20, 2022. The indicators included incidence of hypotension, reactive hypertension, bradycardia, nausea and vomiting, umbilical artery pH, and Apgar scores. RESULTS: About 3125 related records were obtained and 17 RCTs met our eligibility criteria. Based on the results, prophylactic bolus injection of 21-30 mg ephedrine (82%) was the best efficacious option for preventing hypotension, followed by 13-16 µg norepinephrine and 81-120 mg phenylephrine; 121-150 µg phenylephrine had the highest probability (62%) caused reactive hypertension, followed by 11-30 mg ephedrine; phenylephrine was most likely to cause bradycardia in a dose-dependent manner; 81-120 µg phenylephrine had the highest probability (37%) which associated with IONV; 6-12 µg norepinephrine (31%) had the lowest influence on IONV and had highest probability (34%) associated with improving umbilical arterial pH; 13-16 µg norepinephrine had highest probability (67% at 1 min, 49% at 5 min) which associated with improving Apgar scores. CONCLUSIONS: Based on this study, 5-10 mg ephedrine and 13-16 µg norepinephrine prophylactic bolus injection may be the optimum dosage of three drugs prevent spinal-induced hypotension, which has the least impact on maternal and neonatal outcomes.
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Anestesia Obstétrica , Anestesia Raquidea , Hipertensión , Hipotensión , Recién Nacido , Embarazo , Humanos , Femenino , Fenilefrina/efectos adversos , Efedrina/efectos adversos , Norepinefrina/efectos adversos , Vasoconstrictores/efectos adversos , Cesárea/efectos adversos , Bradicardia , Metaanálisis en Red , Teorema de Bayes , Anestesia Raquidea/efectos adversos , Hipotensión/etiología , Hipotensión/prevención & control , Hipertensión/complicaciones , Anestesia Obstétrica/efectos adversos , Método Doble CiegoRESUMEN
Endometriosis (EMS) is a gynecologic disorder associated with infertility and characterized by the endometrial-type mucosa outside the uterine cavity. Currently available treatment modalities are limited to undesirable effects. Thus, in the present study, we sought to study the pathogenesis mechanism of EMS. For this purpose, the ectopic and eutopic endometrial tissues were resected from 86 patients with EMS and 54 infertile patients without EMS, respectively. The regulatory mechanism among HES family bHLH transcription factor 5 (HES5), transforming growth factor-beta (TGF-ß)-induced factor 1 (TGIF1), F-box, and WD repeat domain containing 7 (FBXW7) was studied by performing co-immunoprecipitation, dual-luciferase reporter gene assay, and chromatin immunoprecipitation, respectively. A mouse model of EMS was established to verify the aforementioned regulatory mechanism in vivo. Upregulation of HES5 and TGIF1, as well as downregulation of FBXW7, was observed in EMS endometrial tissues and human endometrial stromal cells (hESCs), respectively. The overexpression of HES5 was found to suppress the FBXW7 transcription and TGIF1 degradation, resulting in the inactivation of the TGF-ß signaling pathway, as well as inhibition of hESC proliferation and invasion, thereby enhancing apoptosis. Results from a mouse model of EMS showed that the presence of HES5 contributed to the alleviation of EMS. Collectively, we attempted to provide a mechanistic insight into the unrecognized roles of the HES5/FBXW7 in EMS progression.
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Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/metabolismo , Endometriosis/metabolismo , Proteína 7 que Contiene Repeticiones F-Box-WD/metabolismo , Infertilidad Femenina/metabolismo , Proteínas Represoras/metabolismo , Transducción de Señal/genética , Factor de Crecimiento Transformador beta/metabolismo , Adulto , Animales , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/genética , Modelos Animales de Enfermedad , Progresión de la Enfermedad , Endometriosis/patología , Endometrio/metabolismo , Proteína 7 que Contiene Repeticiones F-Box-WD/genética , Femenino , Humanos , Infertilidad Femenina/patología , Ratones , Ratones Endogámicos BALB C , Persona de Mediana Edad , Proteínas Represoras/genética , Células del Estroma/metabolismo , TransfecciónRESUMEN
BACKGROUND: Anastomosing hemangioma is an uncommon benign vascular tumor that may be mistaken for a malignancy. The imaging findings of anastomosing hemangioma are not well provided from the previous reports. Herein, in the study, we discuss the imaging findings for one case of retroperitoneal anastomosing hemangioma. CASE PRESENTATION: One 64-year-old female patient had a left retroperitoneal mass that was incidentally detected upon physical examination. A hypoechoic mass with abundant blood flow signals was found by US in the perirenal space. CT and MRI detected a large cystic and solid lesion in the left retroperitoneal space. Plain CT indicated that the internal density was uneven, and the pattern of enhancement was obvious and progressive. MRI-T2WI showed high intensity, DWI showed isointensity, and the mass also showed obvious progressive enhancement. Finally, anastomosing hemangioma was diagnosed via histopathological studies. CONCLUSION: As a rare and benign tumour, anastomosing hemangioma is easily misinterpreted. We suggest that the observation of "genitourinary tract related, well defined, hyperintensity or isointensity on T2WI, isointensity on DWI, and obvious progressive enhancement patterns likely to the vascular enhancement" may consider the diagnosis of AH.
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Hemangioma , Femenino , Hemangioma/diagnóstico por imagen , Humanos , Imagen por Resonancia Magnética , Espacio Retroperitoneal/diagnóstico por imagenRESUMEN
BACKGROUND: Congenital heart disease (CHD) is a class of cardiovascular defects that includes septal defects, outflow tract abnormalities, and valve defects. Human homolog of Drosophila headcase (HECA) is a novel cell cycle regulator whose role in CHD has not been elucidated. This is the first study to determine the frequency of HECA mutations in patients with CHD and the association between HECA variants and CHD. METHODS: In this study, we identified a candidate gene, HECA, by whole-exome sequencing of an atrial septal defect family. To investigate the association between HECA variants and CHD risk, targeted exon sequencing was conducted in 689 individuals with sporadic CHD. We further analyzed the effect of HECA gene abnormalities on cardiomyocyte phenotype behavior and related signaling pathways by Western blotting, reverse transcription-quantitative polymerase chain reaction, and scratch assay. RESULTS: We found a novel de novo mutation, c.409_410insA (p. W137fs), in the HECA gene and identified five rare deleterious variants that met the filtering criteria in 689 individuals with sporadic CHD. Fisher's exact test revealed a significant association between HECA variations and CHD compared with those in gnomADv2-East Asians(p = 0.0027). Further functional analysis suggested that the variant p. W137fs resulted in a deficiency of the normal HECA protein, and HECA deficiency altered AC16 cell cycle progression, increased cell proliferation, and migration, and promoted the activation of the PDGF-BB/PDGFRB/AKT pathway. CONCLUSIONS: Our study identified HECA and its six rare variants, expanding the spectrum of genes associated with CHD pathogenesis in the Chinese population.
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Cardiopatías Congénitas , Defectos del Tabique Interatrial , China/epidemiología , Cardiopatías Congénitas/epidemiología , Cardiopatías Congénitas/genética , Defectos del Tabique Interatrial/genética , Humanos , Mutación/genética , Proteínas de Neoplasias/genética , Secuenciación del ExomaRESUMEN
A novel Ebola virus (EBOV) first identified in March 2014 has infected more than 25,000 people in West Africa, resulting in more than 10,000 deaths. Preliminary analyses of genome sequences of 81 EBOV collected from March to June 2014 from Guinea and Sierra Leone suggest that the 2014 EBOV originated from an independent transmission event from its natural reservoir followed by sustained human-to-human infections. It has been reported that the EBOV genome variation might have an effect on the efficacy of sequence-based virus detection and candidate therapeutics. However, only limited viral information has been available since July 2014, when the outbreak entered a rapid growth phase. Here we describe 175 full-length EBOV genome sequences from five severely stricken districts in Sierra Leone from 28 September to 11 November 2014. We found that the 2014 EBOV has become more phylogenetically and genetically diverse from July to November 2014, characterized by the emergence of multiple novel lineages. The substitution rate for the 2014 EBOV was estimated to be 1.23 × 10(-3) substitutions per site per year (95% highest posterior density interval, 1.04 × 10(-3) to 1.41 × 10(-3) substitutions per site per year), approximating to that observed between previous EBOV outbreaks. The sharp increase in genetic diversity of the 2014 EBOV warrants extensive EBOV surveillance in Sierra Leone, Guinea and Liberia to better understand the viral evolution and transmission dynamics of the ongoing outbreak. These data will facilitate the international efforts to develop vaccines and therapeutics.
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Ebolavirus/genética , Evolución Molecular , Variación Genética/genética , Fiebre Hemorrágica Ebola/epidemiología , Fiebre Hemorrágica Ebola/virología , Secuencia de Bases , Brotes de Enfermedades/estadística & datos numéricos , Ebolavirus/aislamiento & purificación , Monitoreo Epidemiológico , Genoma Viral/genética , Fiebre Hemorrágica Ebola/transmisión , Humanos , Epidemiología Molecular , Tasa de Mutación , Filogenia , Filogeografía , Sierra Leona/epidemiologíaRESUMEN
OBJECTIVE: To explore the relationship between cerebrospinal fluid-contacting neurons (CSF-cNs) and endogenous neural progenitor cells (ENPCs) and whether CSF-cNs are involved in nerve repair after spinal cord injury (SCI). METHODS: Cholera toxin B-horseradish peroxidase complex (CB-HRP) and cholera toxin B conjugated with saporin (CB-SAP) were injected into the lateral ventricles of spinal cord injured rats to mark and destroy the CSF-cNs. Then the rats in the experimental group were injured by SCI. Observe the content and co-expression of CSF-cNs and ENPCs in rats of each group, and observe the recovery of motor function after SCI in each group. RESULTS: After the destruction of CSF-cNs, the number of ENPCs decreased significantly in the long term after the surgery, and the recovery of motor function also deteriorated as compared to the group with intact CSF-cNs. Meanwhile some cells in the spinal cord express both the biological marker of CSF-cNs and ENPCs. CONCLUSION: This study shows that the population of ENPCs and motor function recovery in SCI rats declined after the destruction of CSF-cNs, suggesting that CSF-cNs affect the ENPCs population and may be involved in the recovery of neural function after SCI.
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Líquido Cefalorraquídeo , Ventrículos Laterales , Células-Madre Neurales/fisiología , Neuronas/fisiología , Recuperación de la Función/fisiología , Traumatismos de la Médula Espinal/fisiopatología , Animales , Modelos Animales de Enfermedad , Femenino , Neuronas/efectos de los fármacos , Neuronas/patología , Ratas , Ratas Sprague-DawleyRESUMEN
PURPOSE: Rapid decompressive craniectomy (DC) was the most effective method for the treatment of hypertensive intracerebral hemorrhage (HICH) with cerebral hernia, but the mortality and disability rate is still high. We suspected that hematoma puncture drainage (PD) + DC may improve the therapeutic effect and thus compared the combined surgery with DC alone. METHODS: From December 2013 to July 2019, patients with HICH from Linzhi, Tibet and Honghe, Yunnan Province were retrospectively analyzed. The selection criteria were as follows: (1) altitude ≥1500 m; (2) HICH patients with cerebral hernia; (3) Glascow coma scale score of 4-8 and time from onset to admission ≤3 h; (4) good liver and kidney function; and (5) complete case data. The included patients were divided into DC group and PD + DC group. The patients were followed up for 6 months. The outcome was assessed by Glasgow outcome scale (GOS) score, Kaplan-Meier survival curve and correlation between time from admission to operation and prognosis. A good outcome was defined as independent (GOS score, 4-5) and poor outcome defined as dependent (GOS score, 3-1). All data analyses were performed using SPSS 19, and comparison between two groups was conducted using separate t-tests or Chi-square tests. RESULTS: A total of 65 patients was included. The age ranged 34-90 years (mean, 63.00 ± 14.04 years). Among them, 31 patients had the operation of PD + DC, whereas 34 patients underwent DC. The two groups had no significant difference in the basic characteristics. After 6 months of follow-up, in the PD + DC group there were 8 death, 4 vegetative state, 4 severe disability (GOS score 1-3, poor outcome 51.6 %); 8 moderate disability, and 7 good recovery (GOS score 4-5, good outcome 48.4 %); while in the DC group the result was 15 death, 6 vegetative state, 5 severe disability (poor outcome 76.5 %), 4 moderate disability and 4 good recovery (good outcome 23.5 %). The GOS score and good outcome were significantly less in DC group than in PD + DC group (Z = -1.993, p = 0.046; χ2 = 4.38, p = 0.043). However, there was no significant difference regarding the survival curve between PD + DC group and DC group. The correlation between the time from admission to operation and GOS at 6 months (r = -0.41, R2 = 0.002, p = 0.829) was not significant in the PD + DC group, but significant in the DC group (r = -0.357, R2 = 0.128, p = 0.038). CONCLUSION: PD + DC treatment can improve the good outcomes better than DC treatment for HICH with cerebral hernia at a high altitude.
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Craniectomía Descompresiva , Hemorragia Intracraneal Hipertensiva , Adulto , Anciano , Anciano de 80 o más Años , Altitud , China , Drenaje , Encefalocele/cirugía , Hematoma , Humanos , Hemorragia Intracraneal Hipertensiva/cirugía , Persona de Mediana Edad , Pronóstico , Punciones , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
Osteoarthritis (OA) is a long-term and inflammatory disorder featured by cartilage erosion. Here, we describe nomilin (NOM), a triterpenoid with inflammation modulatory properties in variety of disorders. In this study, we demonstrated the latent mechanism of NOM in alleviating the progress of OA both in vitro and in vivo studies. The results showed that NOM pre-treatment suppressed the IL-1ß-induced over-regulation of pro-inflammation factors, such as NO, IL-6, PGE2 , iNOS, TNF-α and COX-2. Moreover, NOM also down-regulates the degradation of ECM induced by IL-1ß. Mechanistically, the NOM suppressed NF-κB signalling via disassociation of Keap1-Nrf2 in chondrocytes. Furthermore, NOM delays the disease progression in the mouse OA model. To sum up, this research indicated NOM possessed a new potential therapeutic option in osteoarthritis.
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Benzoxepinas/farmacología , Proteína 1 Asociada A ECH Tipo Kelch/metabolismo , Limoninas/farmacología , Factor 2 Relacionado con NF-E2/metabolismo , Osteoartritis/metabolismo , Transducción de Señal/efectos de los fármacos , Animales , Antiinflamatorios/química , Antiinflamatorios/farmacología , Benzoxepinas/química , Biomarcadores , Supervivencia Celular , Condrocitos/metabolismo , Citocinas/metabolismo , Modelos Animales de Enfermedad , Susceptibilidad a Enfermedades , Matriz Extracelular , Femenino , Expresión Génica , Inmunohistoquímica , Mediadores de Inflamación/metabolismo , Limoninas/química , Masculino , Ratones , Modelos Biológicos , FN-kappa B/metabolismo , Osteoartritis/diagnóstico , Osteoartritis/tratamiento farmacológico , Osteoartritis/etiología , RadiografíaRESUMEN
OBJECTIVE: To study the protective effect of asiaticoside against hyperoxia-induced bronchopulmonary dysplasia in neonatal rats based on the microRNA-155 (miR-155)/suppressor of cytokine signaling-1 (SOCS1) axis. METHODS: Neonatal rats were randomly divided into a control group, a model group, a low-dose asiaticoside group (10 mg/kg), a middle-dose asiaticoside group (25 mg/kg), a high-dose asiaticoside group (50 mg/kg), and a budesonide group (1.5 mg/kg), with 12 rats in each group. All rats except those in the control group were exposed to a high concentration of oxygen for 14 days to establish a neonatal rat model of bronchopulmonary dysplasia. The low-, middle-, and high-dose asiaticoside groups were given asiaticoside at different doses by gavage, and those in the budesonide group were given budesonide aerosol treatment. Hematoxylin and eosin staining was used to observe lung tissue development and measure radial alveolar count (RAC) and mean linear intercept (MLI). Superoxide dismutase (SOD) and malondialdehyde (MDA) detection kits were used to measure the levels of SOD and MDA in lung tissue. ELISA was used to measure the serum levels of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6). Quantitative real-time PCR was used to measure the mRNA expression of miR-155 and SOCS1 in lung tissue. Western blotting was used to measure the protein expression of SOCS1 in lung tissue. RESULTS: Compared with the control group, the model group had the symptoms of bronchopulmonary dysplasia such as a disordered structure of lung tissue, enlargement of alveolar fusion, uneven alveolar septa, enlargement of average alveolar space, and a reduction in alveolar number. The model group also had significant increases in MLI, MDA level in lung tissue, serum levels of IL-6 and TNF-α, and miR-155 level in lung tissue (P<0.05) and significant reductions in RAC, SOD level, and mRNA and protein expression of SOCS1 in lung tissue (P<0.05). Compared with the model group, the low-, middle-, and high-dose asiaticoside groups and the budesonide group had significant improvement in the above symptoms of bronchopulmonary dysplasia, significant reductions in MLI, MDA level in lung tissue, serum levels of IL-6 and TNF-α, and miR-155 level in lung tissue (P<0.05), and significant increases in RAC, SOD level, and mRNA and protein expression of SOCS1 in lung tissue (P<0.05). Asiaticoside improved the above symptoms and indices in a dose-dependent manner. There were no significant differences in the above indices between the high-dose asiaticoside and budesonide groups (P>0.05). CONCLUSIONS: Asiaticoside can alleviate inflammation injury induced by hyperoxia in neonatal rats and improve the symptoms of bronchopulmonary dysplasia in a dose-dependent manner, possibly by down-regulating the expression of miR-155 and up-regulating the expression of SOCS1.
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Displasia Broncopulmonar , Hiperoxia , Animales , Animales Recién Nacidos , Pulmón , MicroARNs , Ratas , TriterpenosRESUMEN
The waterborne pathogenic viruses threaten human health. And the nanomaterial-membrane coupling system is promising in virus removal. In this study, phage MS2 was selected as the model virus to investigate the removal of virus with the coupling system. Results revealed that commercial nano TiO2 (Degussa Aeroxide P25) showed both of excellent adsorption and photocatalysis performance for virus removal compared with nano ZnO, nano Fe3O4, carbon nanotube, graphene, nano Ni and Nano TiO2 (anatase). In P25 photocatalysis process, the removal efficiency of phage MS2 increased with the increase of P25 concentration (0~1000 mg L-1), virus initial concentration (102~106 PFU mL-1), UV irradiation doses (5~120 mJ cm-2) and UV light intensity (0.126~0.742 mW cm-2). However, when the P25 concentration increased to over 1000 mg L-1, the virus removal efficiency would remain stable with the increase of P25 concentration. The nanomaterial-membrane coupling system showed excellent performance for virus removal, which was mainly attributed to the adsorption and photocatalysis of P25, and the intercept of membrane. When the P25 concentration was 100 mg L-1, UV irradiation dose was 20 mJ cm-2 and transmembrane pressure was 20 kPa, the phage MS2 removal efficiency could be up to 100%.
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Nanoestructuras , Titanio , Rayos Ultravioleta , Virus/aislamiento & purificación , Purificación del Agua , Adsorción , Catálisis , Grafito , LuzRESUMEN
In this study, extracellular polymeric substances of Aphanizomenon flos-aquae (EPS-A) were investigated in order to explore their effect on astrocytes of zebrafish and potential risk for environment. Astrocytes were treated with varying concentrations of EPS-A, the results showed that EPS-A inhibited astrocytes growth in a dose-and time-dependent manner. With the concentrations of EPS-A increasing, the adherent ability of astrocytes decreased and the number of astrocytes floating in the culture medium increased. When treated with 2.35 µg/mL EPS-A, EPS-A induced cell cycle arrest and made the collapse of mitochondrial membrane potential and then led to astrocytes apoptosis. The results suggested that EPS-A could pose a threat to zebrafish and represent risk for environment, so regularly monitoring the presence of EPS-A was very important in nutrient-rich freshwaters when A. flos-aquae blooms broke out.
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Aphanizomenon/química , Apoptosis/efectos de los fármacos , Astrocitos/efectos de los fármacos , Biopolímeros/toxicidad , Agua Dulce/química , Contaminantes Químicos del Agua/toxicidad , Pez Cebra , Animales , Astrocitos/patología , Biopolímeros/aislamiento & purificación , Puntos de Control del Ciclo Celular/efectos de los fármacos , Células Cultivadas , Relación Dosis-Respuesta a Droga , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Factores de Tiempo , Contaminantes Químicos del Agua/aislamiento & purificaciónRESUMEN
The rabies virus (RABV) G protein is the primary contributor to the pathogenicity and protective immunity of RABV. In this study, we generated a recombinant rCVS-11-G strain containing two copies of the G protein derived from the pathogenic wild-type (wt) CVS-11 strain and based on its infectious clone. Compared with the wtCVS-11 strain, the rCVS-11-G strain possessed a larger virion and 1.4-fold more G protein, but it exhibited a similar growth property to the rCVS-11 strain, including passaging stability in vitro. qPCR results showed that the two G genes were over-expressed in BHK-21 cells infected with the rCVS-11-G strain. However, the rCVS-11-G strain presented an 80 % lower LD50 than the wtCVS-11 strain when intracranially (i.c.) inoculated in adult mice. Adult mice that were either intracranially (i.c.) or intramuscularly (i.m.) inoculated with rCVS-11-G strain developed more acute neurological symptoms and greater mortality than those inoculated with the wtCVS-11 strain. Furthermore, the rCVS-11-G strain was more easily and rapidly taken up by neuroblastoma cells. These data indicated that the rCVS-11-G strain might have increased neurotropism because of the over-expression of the pathogenic G protein. The inactivated rCVS-11-G strain induced significantly higher levels of virus neutralization antibodies and provided better protection from street rabies virus challenge in mice. Therefore, the rCVS-11-G strain may be a promising inactivated vaccine strain due to its better immunogenicity.
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Anticuerpos Neutralizantes/inmunología , Vacunas Antirrábicas/inmunología , Virus de la Rabia/inmunología , Rabia/inmunología , Rabia/prevención & control , Proteínas del Envoltorio Viral/inmunología , Animales , Anticuerpos Antivirales/inmunología , Femenino , Glicoproteínas/administración & dosificación , Glicoproteínas/inmunología , Humanos , Ratones , Ratones Endogámicos BALB C , Rabia/virología , Vacunas Antirrábicas/administración & dosificación , Vacunas Antirrábicas/genética , Virus de la Rabia/genética , Vacunas de Productos Inactivados/administración & dosificación , Vacunas de Productos Inactivados/genética , Vacunas de Productos Inactivados/inmunología , Proteínas del Envoltorio Viral/administración & dosificación , Proteínas del Envoltorio Viral/genéticaRESUMEN
STUDY OBJECTIVE: A Bayesian network meta-analysis was performed to compare the analgesic efficacy of the following nerve block techniques: femoral nerve block (FNB), adductor canal block (ACB), infiltration between the popliteal artery and the capsule of the posterior knee (iPACK), and genicular nerve block (GNB) following total knee arthroplasty (TKA). DESIGN: Systematic review and network meta-analysis (NMA). PATIENTS AND MEASUREMENTS: We searched the Web of Science, PubMed, EMBASE, and Cochrane Library databases until September 20, 2022. Patients who were treated by any of the above four nerve block techniques (alone or in combination) after TKA were included. Patients who underwent minimally invasive knee surgery were excluded. The indicators included pain scores during rest and mobilization, opioid consumption after surgery, postsurgical mobilization function (ROM [range of motion], TUG [Timed-Up-and-Go] test) at 24 h and 48 h, and length of hospital stay. The risk of bias was assessed by the Cochrane risk of bias tool. RESULTS: Forty-two studies involving 2857 patients were eligible for this study. This NMA suggested that ACB + iPACK was the most efficacious option for improving ambulation ability and shortening the length of hospital stay. Furthermore, ACB + iPACK was the best regimen for resting-pain and movement-pain relief (78% and 87%, respectively) and for reducing opioid consumption (90%) at 48 h. However, FNB + iPACK was the most efficacious option for relief of resting pain (42%) and reducing opioid consumption (68%) at 24 h; GNB was the most efficacious option for movement pain relief at 24 h (94%). CONCLUSION: Considering both pain control and knee functional recovery, ACB + iPACK may be the optimal analgesic regimen for patients after TKA. At the same time, it significantly reduces pain and opioid consumption at 48 h. However, ACB + iPACK is not the recommended technique for short-term (24 h) pain control. CLINICAL TRIAL REGISTRATION: PROSPERO (CRD42022362322).
Asunto(s)
Artroplastia de Reemplazo de Rodilla , Teorema de Bayes , Bloqueo Nervioso , Metaanálisis en Red , Dolor Postoperatorio , Humanos , Artroplastia de Reemplazo de Rodilla/efectos adversos , Dolor Postoperatorio/prevención & control , Dolor Postoperatorio/etiología , Bloqueo Nervioso/métodos , Analgésicos Opioides/administración & dosificación , Dimensión del Dolor , Manejo del Dolor/métodos , Resultado del Tratamiento , Nervio Femoral/efectos de los fármacos , Tiempo de Internación/estadística & datos numéricos , Rango del Movimiento Articular/efectos de los fármacosRESUMEN
Rice husks are rich in xylan, which can be hydrolyzed by xylanase to form xylooligosaccharides (XOS). XOS are a functional oligosaccharide such as improving gut microbiota and antioxidant properties. In this study, the structure and functional characteristics of XOS were studied. The optimal xylanase hydrolysis conditions through response surface methodology (RSM) were: xylanase dosage of 3000â¯U/g, hydrolysis time of 3â¯h, hydrolysis temperature of 50⯰C. Under this condition, the yield of XOS was 150.9â¯mg/g. The TG-DTG curve showed that XOS began to decompose at around 200⯰C. When the concentration of XOS reached 1.0â¯g/L, the clearance rate of DPPH reached 65.76â¯%, and the scavenging rate of OH reached 62.10â¯%, while the clearance rate of ABTS free radicals reached 97.70â¯%, which was equivalent to the clearance rate of VC. XOS had a proliferative effect on four probiotics: Lactobacillus plantarum, Lactobacillus brucelli, Lactobacillus acidophilus, and Lactobacillus rhamnosus. However, the further experiments are needed to explore the improvement effect of XOS on human gut microbiota, laying a foundation for the effective utilization of XOS. XOS have a wide range of sources, low price, and broad development prospects. The reasonable utilization of XOS can bring greater economic benefits.
Asunto(s)
Antioxidantes , Glucuronatos , Oligosacáridos , Oryza , Probióticos , Oligosacáridos/farmacología , Oligosacáridos/química , Oryza/química , Glucuronatos/farmacología , Glucuronatos/química , Antioxidantes/farmacología , Antioxidantes/química , Hidrólisis , Endo-1,4-beta Xilanasas/metabolismo , LactobacillusRESUMEN
Objective: The objective of this study is to examine the risk factors associated with the occurrence of PICC-Related Venous Thrombosis (PICC-RVTE) in individuals diagnosed with lymphoma, as well as to develop a predictive risk nomogram model. Methods: A total of 215 patients with lymphoma treated at Yunnan Provincial Tumor Hospital from January 2017 to December 2020 were retrospectively evaluated as the training cohort; 90 patients with lymphoma treated at the Department of Oncology of the First People's Hospital of Anning, Affiliated to Kunming University of Science and Technology during the January 2021 to September 2023 were evaluated as the validation cohort. Independent influencing factors were analyzed by logistic regression, a nomogram was developed and validated, and the model was evaluated using internal and external data cohorts for validation. Results: A total of 305 lymphoma patients were selected and 35 (11.48%) PICC-RVTE occurred, the median time was 13 days. The incidence within 1-2week was 65.71%. Multivariate analysis suggested that the activity amount, thrombosis history(within the last 12 months), ATIII, Total cholesterol and D-dimer levels were independently associated with PICC-RVTE, and a nomogram was constructed based on the multivariate analysis. ROC analysis indicated good discrimination in the training set (area under the curve [AUC] = 0.907, 95%CI:0.850-0.964) and the testing set (AUC = 0.896, 95%CI: 0.782-1.000) for the PICC-RVTE nomogram. The calibration curves showed good calibration abilities, and the decision curves indicated the clinical usefulness of the prediction nomograms. Conclusions: Patients should be advised to undergo color Doppler ultrasound system testing within two week after the implantation of a PICC catheter to detect PICC-RVTE at an early stage. The validated nomogram can be used to predict the risk of catheter-related thrombosis (CRT) in patients with lymphoma who received at least one chemotherapy after PICC catheterization, no bleeding tendency, no recent history of anticoagulant exposure and no severe heart, lung, renal insufficiency. This model has the potential to assist clinicians in formulating individualized treatment strategies for each patient.
RESUMEN
Human endogenous retroviruses (HERVs) are remnants of retroviral infections in human germline cells from millions of years ago. Among these, ERVW-1 (also known as HERV-W-ENV, ERVWE1, or ENVW) encodes the envelope protein of the HERV-W family, which contributes to the pathophysiology of schizophrenia. Additionally, neuropathological studies have revealed cell death and disruption of iron homeostasis in the brains of individuals with schizophrenia. Here, our bioinformatics analysis showed that differentially expressed genes in the human prefrontal cortex RNA microarray dataset (GSE53987) were mainly related to ferroptosis and its associated pathways. Clinical data demonstrated significantly lower expression levels of ferroptosis-related genes, particularly Glutathione peroxidase 4 (GPX4) and solute carrier family 3 member 2 (SLC3A2), in schizophrenia patients compared to normal controls. Further in-depth analyses revealed a significant negative correlation between ERVW-1 expression and the levels of GPX4/SLC3A2 in schizophrenia. Studies indicated that ERVW-1 increased iron levels, malondialdehyde (MDA), and transferrin receptor protein 1 (TFR1) expression while decreasing glutathione (GSH) levels and triggering the loss of mitochondrial membrane potential, suggesting that ERVW-1 can induce ferroptosis. Ongoing research has shown that ERVW-1 reduced the expression of GPX4 and SLC3A2 by inhibiting their promoter activities. Moreover, Ferrostatin-1 (Fer-1), the ferroptosis inhibitor, reversed the iron accumulation and mitochondrial membrane potential loss, as well as restored the expressions of ferroptosis markers GSH, MDA, and TFR1 induced by ERVW-1. In conclusion, ERVW-1 could promote ferroptosis by downregulating the expression of GPX4 and SLC3A2, revealing a novel mechanism by which ERVW-1 contributes to neuronal cell death in schizophrenia.