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Japanese encephalitis virus (JEV) is a mosquito-borne, zoonotic orthoflavivirus causing human encephalitis and reproductive disorders in pigs. Cell-intrinsic antiviral restriction factors are the first line of defense that prevent a virus from establishing a productive infection, while the molecular mechanism of the virus-host interaction is still not fully understood. Our in vitro experiments demonstrated that the Solute Carrier Family 25 Member 12 (SLC25A12) interacted with the JEV nonstructural protein 1 (NS1) and inhibited JEV replication. Furthermore, we showed that knockdown or knockout of SLC25A12 promoted JEV replication, while overexpression of SLC25A12 repressed viral replication. Finally, we demonstrated that SLC25A12 increased IRF7 mRNA levels, which promoted IFN-ß expression and subsequently induced antiviral effects. Collectively, our study revealed that SLC25A12 interacted with NS1, inhibiting viral RNA synthesis and transcription and enhancing type I interferon induction for antiviral effects.
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African swine fever (ASF), caused by the African swine fever virus (ASFV), is a highly infectious disease afflicting domestic pigs and wild boars. It exhibits an alarming acute infection fatality rate of up to 100%. Regrettably, no commercial vaccines or specific drugs for combating this disease are currently available. This study evaluated the anti-ASFV activities in porcine alveolar macrophages, 3D4/21 cells, and PK-15 cells of four bis-benzylisoquinoline alkaloids (BBAs): cepharanthine (CEP), tetrandrine, fangchinoline, and iso-tetrandrine. Furthermore, we demonstrated that CEP, which exhibited the highest selectivity index (SI = 81.31), alkalized late endosomes/lysosomes, hindered ASFV endosomal transport, disrupted virus uncoating signals, and thereby inhibited ASFV internalization. Additionally, CEP disrupted ASFV DNA synthesis, leading to the inhibition of viral replication. Moreover, berbamine was labeled with NBD to synthesize a fluorescent probe to study the cellular location of these BBAs. By co-staining with Lyso-Tracker and lysosome-associated membrane protein 1, we demonstrated that BBAs target the endolysosomal compartments for the first time. Our data together indicated that BBAs are a class of natural products with significant inhibitory effects against ASFV infection. These findings suggest their potential efficacy as agents for the prevention and control of ASF, offering valuable references for the identification of potential drug targets.IMPORTANCEThe urgency and severity of African swine fever (ASF) underscore the critical need for effective interventions against this highly infectious disease, which poses a grave threat to domestic pigs and wild boars. Our study reveals the potent anti-African swine fever virus (ASFV) efficacy of bis-benzylisoquinoline alkaloids (BBAs), particularly evident in the absence of progeny virus production under a 5 µM concentration treatment. The structural similarity among cepharanthine, tetrandrine, fangchinoline, and iso-tetrandrine, coupled with their analogous inhibitory stages and comparable selectivity indexes, strongly suggests a shared antiviral mechanism within this drug category. Further investigation revealed that BBAs localize to lysosomes and inhibit the internalization and replication of ASFV by disrupting the endosomal/lysosomal function. These collective results have profound implications for ASF prevention and control, suggesting the potential of the investigated agents as prophylactic and therapeutic measures. Furthermore, our study offers crucial insights into identifying drug targets and laying the groundwork for innovative interventions.
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Virus de la Fiebre Porcina Africana , Antivirales , Bencilisoquinolinas , Endosomas , Lisosomas , Internalización del Virus , Replicación Viral , Animales , Virus de la Fiebre Porcina Africana/efectos de los fármacos , Virus de la Fiebre Porcina Africana/fisiología , Internalización del Virus/efectos de los fármacos , Bencilisoquinolinas/farmacología , Replicación Viral/efectos de los fármacos , Lisosomas/efectos de los fármacos , Lisosomas/metabolismo , Lisosomas/virología , Porcinos , Endosomas/metabolismo , Endosomas/efectos de los fármacos , Endosomas/virología , Antivirales/farmacología , Línea Celular , Fiebre Porcina Africana/virología , Fiebre Porcina Africana/tratamiento farmacológico , Fiebre Porcina Africana/metabolismo , Guanina/análogos & derivados , Guanina/farmacología , Alcaloides/farmacología , Macrófagos Alveolares/virología , Macrófagos Alveolares/efectos de los fármacos , BenzodioxolesRESUMEN
Urethral stricture (US) is a challenging problem in urology and its pathogenesis of US is closely related to the fibrotic process. Previous evidence has indicated the downregulation of microRNA (miR)-486 in injured urethral specimens of rats. This study aimed to explore the effects of miR-486-overexpressed bone marrow mesenchymal stem cells (BMSCs) on US. BMSCs were identified by detecting their multipotency and surface antigens. Lentivirus virus expressing miR-486 was transduced into rat BMSCs to overexpress miR-486. Transforming growth factor (TGF)-ß1 induced fibrotic phenotypes in urethral fibroblasts (UFs) and rat models. Western blotting showed protein levels of collagen I/III and collagen type XIII alpha 1 chain (Col13a1). Real time quantitative polymerase chain reaction was utilized for messenger RNA level evaluation. Hematoxylin-eosin, Masson's trichrome, and Von Willebrand Factor staining were conducted for histopathological analysis. Immunofluorescence staining was employed for detecting alpha smooth muscle actin (α-SMA) expression. Luciferase reporter assay verified the interaction between miR-486 and Col13a1. The results showed that miR-486-overexpressed BMSCs suppressed collagen I/III and α-SMA expression in TGF-ß1-stimulated UFs. miR-486-overexpressed BMSCs alleviated urethral fibrosis, collagen deposition, and epithelial injury in the urethral tissue of US rats. miR-486 targeted and negatively regulated Col13a1 in US rats. In conclusion, overexpression of miR-486 in BMSCs targets Col13a1 and attenuates urethral fibrosis in TGF-ß1-triggered UFs and US rats.
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African swine fever (ASF) is an acute, febrile, and highly lethal infectious disease in pigs caused by the African swine fever virus (ASFV). Effective detection methods and strict biosecurity measures are crucial for preventing and controlling ASF, especially since there are currently no commercially available vaccines or antiviral drugs to combat ASFV infection effectively. However, the emergence of low-virulence strains of ASFV in recent years has led to false-positive results, highlighting the importance of early-produced antibody detection methods. Therefore, detecting antibodies against ASFV produced early in the infection can facilitate the prompt identification of infected pigs. This study focused on the p30 protein, an early expressed protein during ASFV infection, to develop an indirect ELISA. This method was established using the HEK293F suspension cell expression system, which has the ability to produce large quantities of correctly folded proteins with normal functionality. In this study, we developed an indirect ELISA test utilizing the p30 recombinant protein produced by the HEK293F suspension cell expression system as the antigen coating. The concentration of the p30 protein obtained from the HEK293F suspension cell expression system was measured at 4.668â¯mg/mL, serving as the foundation for establishing the indirect ELISA. Our findings indicate that the indirect ELISA method exhibits a sensitivity of 1:12800. Furthermore, it demonstrates high specificity and excellent reproducibility. Comparing our results to those obtained from the commercial kit, we found a coincidence rate of 98.148â¯% for the indirect ELISA. In summary, we have developed a sensitive method for detecting ASFV, providing a valuable tool for monitoring ASFV infection in pig herds.
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Virus de la Fiebre Porcina Africana , Fiebre Porcina Africana , Anticuerpos Antivirales , Ensayo de Inmunoadsorción Enzimática , Animales , Ensayo de Inmunoadsorción Enzimática/veterinaria , Ensayo de Inmunoadsorción Enzimática/métodos , Fiebre Porcina Africana/diagnóstico , Fiebre Porcina Africana/virología , Fiebre Porcina Africana/inmunología , Porcinos , Células HEK293 , Virus de la Fiebre Porcina Africana/inmunología , Humanos , Proteínas Recombinantes/inmunología , Fosfoproteínas , Proteínas ViralesRESUMEN
Apolipoprotein E (apoE) plays a crucial role in the pathogenesis of Alzheimer's disease (AD). Microglia exhibit a substantial upregulation of apoE in AD-associated circumstances, despite astrocytes being the primary source of apoE expression and secretion in the brain. Although the role of astrocytic apoE in the brain has been extensively investigated, it remains unclear that whether and how apoE particles generated from astrocytes and microglia differ in biological characteristic and function. Here, we demonstrate the differences in size between apoE particles generated from microglia and astrocytes. Microglial apoE particles impair neurite growth and synapses, and promote neuronal senescence, whereas depletion of GPNMB (glycoprotein non-metastatic melanoma protein B) in microglial apoE particles mitigated these deleterious effects. In addition, human APOE4-expressing microglia are more neurotoxic than APOE3-bearing microglia. For the first time, these results offer concrete evidence that apoE particles produced by microglia are involved in neuronal senescence and toxicity.
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The x%Ni/Sm2O3-MnO (x = 0, 10, 15, 20) catalysts derived from SmMn2O5 mullite were prepared by solution combustion and impregnation method; auto-thermal reforming (ATR) of acetic acid (HAc) for hydrogen production was used to explore the metal-support effect induced by Ni loadings on the catalytic reforming activity and product distribution. The 15%Ni/Sm2O3-MnO catalyst exhibited optimal catalytic performance, which can be due to the appropriate Ni loading inducing a strong metal-support interaction to form a stable Ni/Sm2O3-MnO active center, while side reactions, such as methanation and ketonization, were well suppressed. According to characterizations, Sm2O3-MnO mixed oxides derived from SmMn2O5 mullite were formed with oxygen vacancies; nevertheless, loading of Ni metal further promoted the formation of oxygen vacancies, thus enhancing adsorption and activation of oxygen-containing intermediate species and resulting in higher reactivity with HAc conversion near 100% and hydrogen yield at 2.62 mol-H2/mol-HAc.
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The H10 subtype avian influenza virus (AIV) poses an ongoing threat to both birds and humans. Notably, fatal human cases of H10N3 and H10N8 infections have drawn public attention. In 2022, we isolated two H10N3 viruses (A/chicken/Shandong/0101/2022 and A/chicken/Shandong/0603/2022) from diseased chickens in China. Genome analysis revealed that these viruses were genetically associated with human-origin H10N3 virus, with internal genes originating from local H9N2 viruses. Compared to the H10N8 virus (A/chicken/Jiangxi/102/2013), the H10N3 viruses exhibited enhanced thermostability, increased viral release from erythrocytes, and accumulation of hemagglutinin (HA) protein. Additionally, we evaluated the pathogenicity of both H10N3 and H10N8 viruses in mice. We found that viral titers could be detected in the lungs and nasal turbinates of mice infected with the two H10N3 viruses, whereas H10N8 virus titers were detectable in the lungs and brains of mice. Notably, the proportion of double HA Q222R and G228S mutations in H10N3 viruses has increased since 2019. However, the functional roles of the Q222R and G228S double mutations in the HA gene of H10N3 viruses remain unknown and warrant further investigation. Our study highlights the potential public health risk posed by the H10N3 virus. A spillover event of AIV to humans could be a foretaste of a looming pandemic. Therefore, it is imperative to continuously monitor the evolution of the H10N3 influenza virus to ensure targeted prevention and control measures against influenza outbreaks.
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We present the results for the complete next-to-leading order electroweak corrections to ppâHH at the Large Hadron Collider, focusing on the dominant gluon-gluon fusion process. While the corrections at the total cross-section level are approximately -4%, those near the energy of HH production threshold exceed +15%, and corrections at the high-energy region are around -10%, leading to a shape distortion for the differential distributions. Our findings substantially diminish the theoretical uncertainties associated with this pivotal process, providing valuable input for understanding the shape of the Higgs boson potential upon comparison with experimental measurements.
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Inadequate generality across different organs and tasks constrains the application of ultrasound (US) image analysis methods in smart healthcare. Building a universal US foundation model holds the potential to address these issues. Nevertheless, the development of such foundation models encounters intrinsic challenges in US analysis, i.e., insufficient databases, low quality, and ineffective features. In this paper, we present a universal US foundation model, named USFM, generalized to diverse tasks and organs towards label efficient US image analysis. First, a large-scale Multi-organ, Multi-center, and Multi-device US database was built, comprehensively containing over two million US images. Organ-balanced sampling was employed for unbiased learning. Then, USFM is self-supervised pre-trained on the sufficient US database. To extract the effective features from low-quality US images, we proposed a spatial-frequency dual masked image modeling method. A productive spatial noise addition-recovery approach was designed to learn meaningful US information robustly, while a novel frequency band-stop masking learning approach was also employed to extract complex, implicit grayscale distribution and textural variations. Extensive experiments were conducted on the various tasks of segmentation, classification, and image enhancement from diverse organs and diseases. Comparisons with representative US image analysis models illustrate the universality and effectiveness of USFM. The label efficiency experiments suggest the USFM obtains robust performance with only 20% annotation, laying the groundwork for the rapid development of US models in clinical practices.
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Ultrasonografía , Humanos , Ultrasonografía/métodos , Procesamiento de Imagen Asistido por Computador/métodos , Algoritmos , Bases de Datos Factuales , Interpretación de Imagen Asistida por Computador/métodosRESUMEN
BACKGROUND: Venous thromboembolism (VTE) is a major complication of breast cancer surgical patients. Assessing VTE awareness enables medical staff to tailor educational programs that improve patient self-management and reduce VTE risk. Therefore, this study aimed to assess VTE awareness among breast cancer surgical patients and identify factors influencing their awareness level. METHODS: A multicenter cross-sectional study was conducted on breast cancer patients scheduled for surgery from May 2023 to November 2023. Data were collected using a general information form and a validated self-assessment questionnaire on VTE awareness for breast cancer surgical patients. Univariate analysis and multiple linear regression analysis were used to analyze the data. RESULTS: Of 1969 patients included, the term awareness rates for deep vein thrombosis and pulmonary embolism were 42.5% and 26.1%, respectively. Information about VTE was primarily obtained from doctors (30.4%), nurses (24.0%), and social media (23.3%). The overall average VTE awareness score was 1.55 ± 0.53, with the dimension of VTE preventive measures scoring highest, and VTE clinical symptoms/signs scoring lowest. Multivariate analysis identified education level, personal VTE history, chemotherapy and surgical history, and the hospital's regional location as significant factors associated with VTE awareness level (p < 0.05). CONCLUSION: This study highlights a critical need for improved VTE awareness among breast cancer surgical patients, particularly regarding clinical symptoms/signs. Health education programs are recommended especially tailored for patients with lower education levels, no history of VTE, or without prior surgery or chemotherapy, to improve their understanding of VTE.
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Neoplasias de la Mama , Conocimientos, Actitudes y Práctica en Salud , Tromboembolia Venosa , Humanos , Femenino , Estudios Transversales , Neoplasias de la Mama/cirugía , Neoplasias de la Mama/complicaciones , Tromboembolia Venosa/etiología , Tromboembolia Venosa/prevención & control , Tromboembolia Venosa/epidemiología , Persona de Mediana Edad , Adulto , Factores de Riesgo , Encuestas y Cuestionarios , Anciano , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/prevención & controlRESUMEN
In this study, a sensitive high-performance liquid chromatography detector was established and validated for the simultaneous determination of geniposide, ellagic acid, piperine, costunolide and dehydrocostuslactone in Liuwei Muxiang Capsules. The analysis was achieved on CHANIN 100-5-C18-H column (5µm, 250 mm×4.6 mm) with the temperature of 30oC. Gradient elution was applied using 0.1% phosphoric acid solution-methanol-acetonitrile (50:50) as mobile phase at the flow rate of 1.0 mL/min. The determination was performed at the wavelength of 225 nm (detecting geniposide), 254 nm (detecting ellagic acid), 343 nm (detecting piperine) and 225 nm (detecting costunolide and dehydrocostuslactone) along with the sample volume of 10µL. The linear ranges of geniposide, ellagic acid, piperine, costunolide and dehydrocostuslactone demonstrated good linear relationships within their respective determination ranges. The average recoveries were 100.04%, 99.86%, 99.79%, 100.17% and 100.41%, respectively. RSD% was 1.3%, 1.2%, 1.2%, 1.2%, 1.5%, respectively. The developed method was proved to be simple, accurate and sensitive, which can provide a quantitative analysis method for the content determination of geniposide, ellagic acid, piperine, costunolide and dehydrocostuslactone in Liuwei Muxiang capsules.
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Alcaloides , Benzodioxoles , Cápsulas , Medicamentos Herbarios Chinos , Ácido Elágico , Iridoides , Lactonas , Piperidinas , Alcamidas Poliinsaturadas , Cromatografía Líquida de Alta Presión/métodos , Benzodioxoles/análisis , Alcamidas Poliinsaturadas/análisis , Piperidinas/análisis , Piperidinas/química , Alcaloides/análisis , Lactonas/análisis , Medicamentos Herbarios Chinos/química , Medicamentos Herbarios Chinos/análisis , Iridoides/análisis , Ácido Elágico/análisis , Reproducibilidad de los Resultados , Sesquiterpenos/análisisRESUMEN
Domain shift problem is commonplace for ultrasound image analysis due to difference imaging setting and diverse medical centers, which lead to poor generalizability of deep learning-based methods. Multi-Source Domain Transformation (MSDT) provides a promising way to tackle the performance degeneration caused by the domain shift, which is more practical and challenging compared to conventional single-source transformation tasks. An effective unsupervised domain combination strategy is highly required to handle multiple domains without annotations. Fidelity and quality of generated images are also important to ensure the accuracy of computer-aided diagnosis. However, existing MSDT approaches underperform in above two areas. In this paper, an efficient domain transformation model named M2O-DiffGAN is introduced to achieve a unified mapping from multiple unlabeled source domains to the target domain. A cycle-consistent "many-to-one" adversarial learning architecture is introduced to model various unlabeled domains jointly. A condition adversarial diffusion process is employed to generate images with high-fidelity, combining an adversarial projector to capture reverse transition probabilities over large step sizes for accelerating sampling. Considering the limited perceptual information of ultrasound images, an ultrasound-specific content loss helps to capture more perceptual features for synthesizing high-quality ultrasound images. Massive comparisons on six clinical datasets covering thyroid, carotid and breast demonstrate the superiority of the M2O-DiffGAN in the performance of bridging the domain gaps and enlarging the generalization of downstream analysis methods compared to state-of-the-art algorithms. It improves the mean MI, Bhattacharyya Coefficient, dice and IoU assessments by 0.390, 0.120, 0.245 and 0.250, presenting promising clinical applications.
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Ultrasonografía , Humanos , Ultrasonografía/métodos , Aprendizaje Profundo , Algoritmos , Interpretación de Imagen Asistida por Computador/métodosRESUMEN
OBJECTIVE: This study aims to investigate the cardiac protective effects and molecular mechanisms of electroacupuncture (EA) pre-treatment in lipopolysaccharide (LPS)-Induced Cardiomyopathy. METHODS AND RESULTS: Pre-treatment with EA was performed 30 min before intraperitoneal injection of LPS. Cardiac function changes in mice of the EA + LPS group were observed using electrocardiography, echocardiography, and enzyme linked immunosorbent assay (ELISA) and compared with the LPS group. The results demonstrated that EA pre-treatment significantly improved the survival rate of septic mice, alleviated the severity of endotoxemia, and exhibited notable cardiac protective effects. These effects were characterized by a reduction in ST-segment elevation on electrocardiography, an increase in ejection fraction (EF) and fraction shortening (FS) on echocardiography and a decrease in the expression of serum cardiac troponin I (cTn-I) levels. Serum exosomes obtained after EA pre-treatment were extracted and administered to septic mice, revealing significant cardiac protective effects of EA-derived exosomes. Furthermore, the antagonism of circulating exosomes in mice markedly suppressed the cardiac protective effects conferred by EA pre-treatment. Analysis of serum exosomes using quantitative reverse transcription-polymerase chain reaction (qRT-PCR) revealed a significant upregulation of miR-381 expression after EA pre-treatment. Inhibition or overexpression of miR-381 through serotype 9 adeno-associated virus (AAV9)-mediated gene delivery demonstrated that overexpression of miR-381 exerted a cardiac protective effect, while inhibition of miR-381 significantly attenuated the cardiac protective effects conferred by EA pre-treatment. CONCLUSIONS: Our research findings have revealed a novel endogenous cardiac protection mechanism, wherein circulating exosomes derived from EA pre-treatment mitigate LPS-induced cardiac dysfunction via miR-381.
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Cardiomiopatías , Electroacupuntura , Exosomas , Lipopolisacáridos , MicroARNs , Animales , MicroARNs/genética , MicroARNs/metabolismo , Exosomas/metabolismo , Exosomas/genética , Electroacupuntura/métodos , Ratones , Cardiomiopatías/inducido químicamente , Cardiomiopatías/metabolismo , Cardiomiopatías/terapia , Cardiomiopatías/patología , Cardiomiopatías/genética , Cardiomiopatías/prevención & control , Lipopolisacáridos/toxicidad , Masculino , Ratones Endogámicos C57BL , Modelos Animales de EnfermedadRESUMEN
BACKGROUND: The anatomy of myocardial fibers around the right cardiac veins (RCVs) and their roles in accessory pathways (APs) are rarely reported. METHODS: Six RCV-APs were identified from 566 patients with right-sided APs. Mapping of retrograde atrial activation was performed using CARTO 3 system under orthodromic tachycardia or right ventricular pacing. Venography of RCVs was acquired at the earliest retrograde atrial activation. RESULTS: Patients enrolled had a median age of 30 (11-51) years, 5 of them were male. Venography of RCVs could be classified into 3 distinct patterns based on the identified ventricular branches, right marginal vein only (type I; n=3), both right marginal vein and anterior cardiac veins (type II; n=2), and anterior cardiac vein only (type III; n=1). Patients with type I venography had rS QRS pattern in lead V1, negative delta wave in lead III and negative or isoelectric delta wave in lead aVF. However, patients with type II and III venography had QS QRS patterns in lead V1 and variable patterns of delta wave in inferior leads. Earliest retrograde atrial activation was found at a median of 16.75 (14.60-20.00) mm away from the tricuspid annulus, all with A larger than V. At the earliest retrograde atrial activation, far-field ventricular electrogram was found 30 ms later than QRS onset in 1 patient under sinus rhythm. AP conduction was eliminated by mechanical pressure in 2 and by radiofrequency ablation in 4 at the ostium of the veins colocalizing with the earliest retrograde activation of the right atrium. No recurrence was observed during 36 (10-60) months follow-up. CONCLUSIONS: The RCV-AP is a rare form of right-sided APs characterized by atrial insertions distant from the annulus. ECG-speculated ventricular insertion sites conformed to the location of identified RCVs.
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Fascículo Atrioventricular Accesorio , Ablación por Catéter , Flebografía , Humanos , Masculino , Adulto , Femenino , Persona de Mediana Edad , Fascículo Atrioventricular Accesorio/fisiopatología , Fascículo Atrioventricular Accesorio/cirugía , Adolescente , Adulto Joven , Niño , Técnicas Electrofisiológicas Cardíacas , Vasos Coronarios/fisiopatología , Vasos Coronarios/diagnóstico por imagen , Potenciales de Acción , Frecuencia Cardíaca , Estimulación Cardíaca ArtificialRESUMEN
Japanese encephalitis virus (JEV) is a pathogen with a substantial impact on both livestock and human health. However, the critical host factors in the virus life cycle remain poorly understood. Using a library comprising 123411 small guide RNAs (sgRNAs) targeting 19050 human genes, we conducted a genome-wide clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9-based screen to identify essential genes for JEV replication. By employing knockout or knockdown techniques on genes, we identified eleven human genes crucial for JEV replication, such as prolactin releasing hormone receptor (PRLHR), activating signal cointegrator 1 complex subunit 3 (ASCC3), acyl-CoA synthetase long chain family member 3 (ACSL3), and others. Notably, we found that PRLHR knockdown blocked the autophagic flux, thereby inhibiting JEV infection. Taken together, these findings provide effective data for studying important host factors of JEV replication and scientific data for selecting antiviral drug targets.
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Sistemas CRISPR-Cas , Virus de la Encefalitis Japonesa (Especie) , ARN Guía de Sistemas CRISPR-Cas , Replicación Viral , Replicación Viral/genética , Virus de la Encefalitis Japonesa (Especie)/genética , Virus de la Encefalitis Japonesa (Especie)/fisiología , Humanos , ARN Guía de Sistemas CRISPR-Cas/genética , Biblioteca de Genes , Animales , Interacciones Huésped-Patógeno/genética , Encefalitis Japonesa/virología , Línea Celular , Células HEK293 , Repeticiones Palindrómicas Cortas Agrupadas y Regularmente EspaciadasRESUMEN
Objective: Systemic studies on anti-PD-1 therapy in patients with metastatic colorectal cancer (mCRC) with microsatellite instability or mismatch repair defects are lacking. We aimed to summarize the evidence regarding the efficacy and safety of pembrolizumab, nivolumab, ipilimumab, and tislelizumab in mCRC. Methods: Network meta-analyses (NMAs) can provide comparative efficacy and safety data for clinical decision-making. In this NMA, eligible publications from PubMed, EMBASE, Web of Science, and Cochrane Library from 2016 to April 2023 were identified through a systematic literature review. Literature screening and data extraction were performed according to established criteria. The quality of the literature was evaluated using the Cochrane risk of bias tool, and statistical analysis was performed using Revman5.4 and R language. The main outcome indicators, DCR, ORR, PFS, and OS, were used to evaluate the effectiveness of the drugs, and the main outcome indicators AE and SAE were used to evaluate the safety of each program. Results: Fifteen studies with a sample size of 798 patients were included. In terms of effectiveness, the disease control rate DCR of PD-1 inhibitors was 0.727[95% CI:0.654-0.794]; objective response rate ORR was 0.448[95% CI:0.382-0.514]; and the 1-year progression-free survival rate was 0.551[95% CI:0.458-0.642]. The 1-year overall survival rate was 0.790[95% CI:0.705-0.865]. The adverse events associated with anti-PD-1 were 0.567[95% CI:0.344-0.778] in terms of safety. The total incidence of grade 3 or higher adverse events was 0.241[95% CI:0.174-0.313]. In the subgroup analysis results, the incidence of DCR in the nivolumab + ipilimumab group was 0.826[95% CI:0.780-0.869], the ORR was 0.512[95% CI:0.377-0.647], and the PFS was 0.668[95% CI:0.516-0.804]. The incidence of AE was 0.319 [95% CI:0.039-0.700] and SAE was 0.294 [95% CI:0.171-0.433]... (AU)
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Humanos , Neoplasias Colorrectales , Metástasis de la Neoplasia , Nivolumab , Ipilimumab , Preparaciones FarmacéuticasRESUMEN
A simple, feasible, isocratic elution, and stable reversed-phase high performance liquid chromatography method was established and verified. The chromatographic conditions are as follows: EF-C18H, 4.6 × 250 mm, 5 µm column; column temperature 30 °C; for the mobile phase 27.2 g of KH2PO4 and 8.5 g of tetrabutylammonium hydrogen sulfate were taken, 2500 mL of water was added to dissolve, and the pH was adjusted to 6.7 with phosphoric acid:methanol solution with a ratio of 84:16 (V:V). The flow rate was 1.0 mL/min; the injection volume was 10 µL; and the wavelength was 262 nm. According to the current ICH guidelines, the developed method was verified, and the system suitability, specificity, LOD, LOQ, linearity, range, accuracy, repeatability, durability, and solution stability of the proposed method were verified. The validation results demonstrated that the LOQ for the method was 0.05% and the LOD was 0.02%. The content was detected within the concentration range of 300 to 900 µg/mL. The relationship between concentration and measurement was linear, with an r2 of >0.999. The concentration of impurities ranged from 0.3 to 4.5 µg/mL. A good linear correlation was observed within the range of g/mL, with a coefficient of determination r2 greater than 0.999. The accuracy and repeatability met the specified criteria.
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The fear of COVID-19 significantly impacting the health of people globally. This study translated newly developed measurement tool New Fear of the Coronavirus Questionnaire (New_FCQ) into Chinese language and evaluated the psychometric properties of the Chinese version of New_FCQ among Chinese population. A total of 522 participants were included in the study. Internal consistency, construct validity, criterion validity, and concurrent validity of the Chinese version of New_FCQ were assessed in this study. The Chinese version of New_FCQ had excellent internal consistency (αâ =â 0.97) and exploratory factor analysis demonstrated one-dimensional structure of the Chinese version of New_FCQ. The preliminary criterion validity revealed statistically significant differences in the fear of COVID-19 scores based on age and education level (Pâ =â .002 and Pâ =â .03, respectively). The good concurrent validity also established with the Chinese version Fear of COVID-19 Scale(Pâ <â .001). Psychometric proportions of the Chinese version of New_FCQ were established, which exhibited sufficient validity and reliability among Chinese population.