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INTRODUCTION: Fully covered self-expandable metal stents (FCSEMSs) are commonly placed in patients with biliary stricture during endoscopic retrograde cholangiopancreatography (ERCP). However, up to 40% of migration has been reported, resulting in treatment failure or the requirement for further intervention. Here, we aimed to investigate the effects of metal clip anchoring on preventing the migration of FCSEMS. METHODS: Consecutive patients requiring placement of FCSEMS were included in this multicenter randomized trial. The enrolled patients were randomly assigned in a 1:1 ratio to receive clip anchoring (clip group) or not (control group). The primary outcome was the migration rate at 6 months after stent insertion. The secondary outcomes were the rates of proximal and distal migration and stent-related adverse events. The analysis followed the intention-to-treat principle. RESULTS: From February 2020 to November 2022, 180 patients with biliary stricture were enrolled, with 90 in each group. The baseline characteristics were comparable between the 2 groups. The overall rate of stent migration at 6 months was significantly lower in the clip group compared with the control group (16.7% vs 30.0%, P = 0.030). The proximal and distal migration rates were similar in the 2 groups (2.2% vs 5.6%, P = 0.205; 14.4% vs 22.2%, P = 0.070). Notably, none of the patients (0/8) who received 2 or more clips experienced stent migration. There were no significant differences in stent-related adverse events between the 2 groups. DISCUSSION: Our data suggest that clip-assisted anchoring is an effective and safe method for preventing migration of FCSEMS without increasing the adverse events.
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BACKGROUND: Pulmonary arterial hypertension (PAH) is a life-threatening chronic cardiopulmonary disease. However, there is a paucity of studies that reflect the available biomarkers from separate gene expression profiles in PAH. METHODS: The GSE131793 and GSE113439 datasets were combined for subsequent analyses, and batch effects were removed. Bioinformatic analysis was then performed to identify differentially expressed genes (DEGs). Weighted gene co-expression network analysis (WGCNA) and a protein-protein interaction (PPI) network analysis were then used to further filter the hub genes. Functional enrichment analysis of the intersection genes was performed using Gene Ontology (GO), Disease Ontology (DO), Kyoto encyclopedia of genes and genomes (KEGG) and gene set enrichment analysis (GSEA). The expression level and diagnostic value of hub gene expression in pulmonary arterial hypertension (PAH) patients were also analyzed in the validation datasets GSE53408 and GSE22356. In addition, target gene expression was validated in the lungs of a monocrotaline (MCT)-induced pulmonary hypertension (PH) rat model and in the serum of PAH patients. RESULTS: A total of 914 differentially expressed genes (DEGs) were identified, with 722 upregulated and 192 downregulated genes. The key module relevant to PAH was selected using WGCNA. By combining the DEGs and the key module of WGCNA, 807 genes were selected. Furthermore, protein-protein interaction (PPI) network analysis identified HSP90AA1, CD8A, HIF1A, CXCL8, EPRS1, POLR2B, TFRC, and PTGS2 as hub genes. The GSE53408 and GSE22356 datasets were used to evaluate the expression of TFRC, which also showed robust diagnostic value. According to GSEA enrichment analysis, PAH-relevant biological functions and pathways were enriched in patients with high TFRC levels. Furthermore, TFRC expression was found to be upregulated in the lung tissues of our experimental PH rat model compared to those of the controls, and the same conclusion was reached in the serum of the PAH patients. CONCLUSIONS: According to our bioinformatics analysis, the observed increase of TFRC in the lung tissue of human PAH patients, as indicated by transcriptomic data, is consistent with the alterations observed in PAH patients and rodent models. These data suggest that TFRC may serve as a potential biomarker for PAH.
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Biología Computacional , Hipertensión Arterial Pulmonar , Animales , Ratas , Biología Computacional/métodos , Humanos , Hipertensión Arterial Pulmonar/genética , Hipertensión Arterial Pulmonar/diagnóstico , Hipertensión Arterial Pulmonar/metabolismo , Masculino , Biomarcadores/sangre , Biomarcadores/metabolismo , Ratas Sprague-Dawley , Mapas de Interacción de Proteínas/genética , Perfilación de la Expresión Génica/métodos , Bases de Datos GenéticasRESUMEN
BACKGROUND: Childhood trauma has been linked to increased risk of schizophrenia and social dysfunction, and oxytocin and its receptor gene have been implicated in regulating social behavior. This study investigated the potential role of oxytocin and oxytocin receptor gene (OXTR) in mediating the effects of childhood trauma on social functioning in schizophrenia. METHODS: The study consisted of 382 patients with schizophrenia and 178 healthy controls who were assessed using the Taiwanese version of the Childhood Trauma Questionnaire (CTQ-SF), the Social Functioning Scale (SFS), and plasma oxytocin levels. DNA was extracted to genotype the OXTR and ten single-nucleotide polymorphisms (SNPs; rs2254298, rs237885, rs237887, rs237899, rs53576, rs9840864, rs13316193, rs7632287, rs1042778, and rs237895) were selected. RESULTS: Patients with schizophrenia showed higher CTQ-SF scores (t = 12.549, p < 0.001), lower SFS scores (t = -46.951, p < 0.001), and lower plasma oxytocin levels (t = -5.448, p < 0.001) compared to healthy controls. The study also found significant differences in OXTR SNPs between both groups, with risk alleles being more prevalent in patients with schizophrenia (t = 2.734, p = 0.006). Results indicated a significant moderated mediation effect, with oxytocin and the OXTR SNPs partially mediating the relationship between childhood trauma exposure and social functioning in patients with schizophrenia (index of mediation = 0.038, 95% CI [0.033-0.044]). CONCLUSIONS: The findings suggest that oxytocin and its receptor gene may be promising targets for interventions aimed at improving social functioning in patients with a history of childhood trauma and schizophrenia. However, further research is needed to fully understand these effects and the potential of oxytocin-based interventions in this population.
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Experiencias Adversas de la Infancia , Pruebas Psicológicas , Esquizofrenia , Autoinforme , Humanos , Genotipo , Oxitocina , Polimorfismo de Nucleótido Simple , Receptores de Oxitocina/genética , Esquizofrenia/genética , Interacción SocialRESUMEN
Aquaculture is one of the fastest growing sectors in global food production, recognized as a significant contributor to poverty alleviation, food security, and income generation. However, the frequent occurrence of diseases caused by pathogen infections result in reduced yields and economic losses, posing a substantial constraint to the sustainable development of aquaculture. Here, our study identified that four catechol compounds, quercetin, luteolin, caffeic acid, and chlorogenic acid, exhibited potent antiparasitic effects against Ichthyophthirius multifiliis in both, in vitro and in vivo. The parasite is recognized as one of the most pathogenic to fish worldwide. Using a combination of in silico methods, the dipeptidyl peptidase (DPP) was identified as a critical target for catechol compounds. The two hydroxyl radicals of the catechol group were essential for its binding to and interacting with the DPP protein. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses indicated that catechol compounds disrupt pathways associated with the metabolism and growth of I. multifiliis, thereby exerting antiparasitic effects. Furthermore, these compounds attenuated the expression of proinflammatory cytokines in vivo in fish and promoted macrophage polarization toward M2 phenotype by inhibiting the STAT1 signaling pathway. The dual activity of catechol compounds, acting as both direct antiparasitic and anti-inflammatory agents in fish, offers a promising therapeutic approach for combating I. multifiliis infections in aquaculture.
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Catecoles , Infecciones por Cilióforos , Enfermedades de los Peces , Hymenostomatida , Animales , Enfermedades de los Peces/inmunología , Enfermedades de los Peces/parasitología , Enfermedades de los Peces/prevención & control , Hymenostomatida/efectos de los fármacos , Catecoles/farmacología , Infecciones por Cilióforos/veterinaria , Infecciones por Cilióforos/inmunología , Infecciones por Cilióforos/parasitología , Infecciones por Cilióforos/prevención & control , Antiparasitarios/farmacologíaRESUMEN
PURPOSE: The influence of Open Access (OA) on the citation impact of scholarly articles remains a topic of considerable debate. This study aims to elucidate the relationship between OA publication and citation metrics, as well as article visibility, within the context of the Postgraduate Medical Journal (PMJ). METHODS: We conducted a retrospective analysis of 373 articles published in PMJ between 2020 and 2021. Data on OA status, citations, page views, PDF downloads, and other relevant variables were extracted from Journal Citation Reports and PMJ's official website. Multivariable linear regression and other statistical analyses were used to assess the impact of OA on these metrics. RESULTS: OA articles (n = 78) demonstrated significantly higher citation counts, page views, and PDF downloads compared with subscription-based articles (n = 295). Specifically, OA articles showed a significant increase in citation frequency with a ß coefficient of 25.08 and a 95% CI of 17.168-32.992 (P < .001). Similarly, OA status was independently associated with increases in page views [ß = 288.636, 95%CI: 177.749-399.524, P < .001] and PDF downloads [ß = 118.966, 95%CI: 86.357-151.575, P < .001]. Strong correlations among total citations, page views, and PDF downloads were observed in both OA and subscription articles. CONCLUSION: The study highlights a significant and independent association of OA publishing with increased citation counts, page views, and PDF downloads in PMJ, suggesting that OA articles have broader reach and greater visibility. Further research, including randomized controlled studies across various journals, is needed to confirm these findings and explore the full impact of OA publishing.
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Bibliometría , Publicaciones Periódicas como Asunto , Humanos , Publicaciones Periódicas como Asunto/estadística & datos numéricos , Estudios Retrospectivos , Publicación de Acceso Abierto , Acceso a la Información , Edición/estadística & datos numéricos , Factor de Impacto de la RevistaRESUMEN
OBJECTIVE: This study aimed to explore the associations of orofacial two-point discrimination (2-PD) test result with pain symptoms and psychological factors in patients with Temporomandibular Disorders (TMDs). METHODS: 193 patients with TMDs were included in this study. Patients' demographics, pain intensity, and psychological status were recorded. The 2-PDs in the bilateral temporal, zygomatic, mandibular, and temporomandibular joint (TMJ) regions of the patients were measured. Statistical analyses were conducted to observe the associations between variables. RESULTS: For Pain-related TMDs (PT) patients, Monthly Visual Analogue Scale (VAS-M) and Current Analogue Scale (VAS-C) were correlated with TMJ, zygomatic and temporal 2-PDs. Patients with PT tended to have higher TMJ 2-PDs[Right: ß = 1.827 mm, 95%CI(0.107, 3.548), P = 0.038], zygomatic 2-PDs[Right: ß = 1.696 mm, 95%CI(0.344, 3.048), P = 0.014], temporal 2-PDs[Left: ß = 2.138 mm, 95%CI(0.127, 4.149), P = 0.037; Right: ß = 1.893 mm, 95%CI(0.011, 3.775), P = 0.049]. Associations were also observed between VAS-C and TMJ 2-PDs[Left: ß = 0.780, 95%CI(0.190, 1.370), P = 0.01; Right: ß = 0.885, 95%CI(0.406, 1.364), P = 0.001], Zygomatic 2-PDs[Right: ß = 0.555, 95%CI(0.172, 0.938), P = 0.005]; VAS-M and TMJ 2-PDs[Left: ß = 0.812, 95%CI(0.313, 1.311), P = 0.002; Right: ß = 0.567, 95%CI(0.152, 0.983), P = 0.008], zygomatic 2-PDs[Left: ß = 0.405, 95%CI(0.075, 0.735), P = 0.016; Right: ß = 0.545, 95%CI(0.221, 0.870), P = 0.001], and temporal 2-PDs [Left: ß = 0.741, 95%CI(0.258, 1.224), P = 0.003; Right: ß = 0.519, 95%CI(0.063, 0.975), P = 0.026]. CONCLUSION: TMJ, zygomatic, and temporal 2-PDs were significantly associated with PT and pain intensity. Age, gender and psychological factors were not associated with orofacial 2-PDs. PT patients exhibited weaker tactile acuity compared to Non-PT patients. Further discussion on the underlying mechanism is needed. CLINICAL RELEVANCE: Orofacial tactile acuity of TMDs patients was associated with their pain symptoms, which researchers should take account into when performing 2-PD tests for TMDs patients. The 2-PD test can be considered as a potential tool along with the current procedures for the differentiations of PT and Non-PT.
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Dolor Facial , Dimensión del Dolor , Trastornos de la Articulación Temporomandibular , Humanos , Trastornos de la Articulación Temporomandibular/fisiopatología , Trastornos de la Articulación Temporomandibular/psicología , Femenino , Masculino , Adulto , Dolor Facial/fisiopatología , Persona de Mediana Edad , Adolescente , Umbral del Dolor/fisiologíaRESUMEN
OBJECTIVE: Persistent infection with high-risk human papillomavirus (HPV) is a key contributor to cervical intraepithelial neoplasia (CIN), but the relation between high-risk HPV genotypes and the location of CIN lesions remains unclear. The aims of this study were to investigate the most frequent biopsy site of CIN lesions in women with different HPV infection and to analyze the biopsy times, CIN frequency, and the clustering of CIN frequency based on 12-o'clock sites and cervical quadrant locations. MATERIALS AND METHOD: We conducted a retrospective study of HPV detection and genotyping at the virology department of our hospital. Colposcopy exams were performed by specialists according to a standardized protocol, and all visually abnormal areas were further biopsied. Pearson chi-squared tests and cluster analyses were implemented to analyze the data. RESULTS: Among 1,381 women enrolled in this study, 933 cases infected with HPV. HPV16, HPV58, and HPV18 were the most common genotypes. The most frequent biopsy site was the 6 o'clock position. The highest frequency of high-grade CIN findings in single-genotype HPV groups was the 6 o'clock position and that for multiple-genotype HPV group was the 12 o'clock location. All CIN clusters were found in the 6 and 12 o'clock biopsy sites, except in the HPV18 group. Quadrant 2 and 4 were clustered in most groups. CONCLUSIONS: The 6 and 12 o'clock sites in cervical quadrant 2 and 4 should be targeted during cervical biopsy procedures. These findings can provide clinicians with specific recommendations on the optimal site for CIN biopsy when considering the HPV genotype.
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Genotipo , Papillomaviridae , Infecciones por Papillomavirus , Displasia del Cuello del Útero , Humanos , Femenino , Displasia del Cuello del Útero/virología , Displasia del Cuello del Útero/patología , Displasia del Cuello del Útero/epidemiología , Estudios Retrospectivos , China/epidemiología , Adulto , Infecciones por Papillomavirus/virología , Infecciones por Papillomavirus/patología , Persona de Mediana Edad , Papillomaviridae/genética , Papillomaviridae/aislamiento & purificación , Papillomaviridae/clasificación , Adulto Joven , Biopsia , Neoplasias del Cuello Uterino/virología , Neoplasias del Cuello Uterino/patología , Anciano , Adolescente , Colposcopía , Virus del Papiloma HumanoRESUMEN
Cultivating microalgae in wastewater offers various advantages, but it still faces limitations such as bacteria and other impurities in wastewater affecting the growth and purity of microalgae, difficulty in microalgae harvesting, and extracellular products of microalgae affecting effluent quality. In this study, a novel dialysis bag-microalgae photobioreactor (Db-PBR) was developed to achieve wastewater purification and purer bioresource recovery by culturing microalgae in a dialysis bag. The dialysis bag in the Db-PBR effectively captured the microalgae cells and promoted their lipid accumulation, leading to higher biomass (1.53 times of the control) and lipid production (2.50 times of the control). During the stable operation stage of Db-PBR, the average soluble microbial products (SMP) content outside the dialysis bag was 25.83 mg L-1, which was significantly lower than that inside the dialysis bag (185.63 mg L-1), indicating that the dialysis bag effectively intercepted the SMP secreted by microalgae. As a result, the concentration of dissolved organic carbon (DOC) in Db-PBR effluent was significantly lower than that of traditional photobioreactor. Furthermore, benefiting from the dialysis bag in the reactor effectively intercepted the microorganisms in wastewater, significantly improving the purity of the cultured microalgae biomass, which is beneficial for the development of high-value microalgae products.
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Microalgas , Purificación del Agua , Aguas Residuales , Fotobiorreactores/microbiología , Diálisis Renal , Biomasa , LípidosRESUMEN
The rapid growth of internet users in China presents opportunities for advancing the "Healthy China 2030" initiative through online health education. Platforms like "Shanghai Health Cloud" and "National Health Information Platform" improve health literacy and management, enhancing overall public health. However, challenges such as the digital divide and the spread of unverified health information hinder progress. Addressing these issues requires enhancing digital infrastructure, employing advanced technologies for information validation, and setting high standards for online health services. Integrated efforts from various sectors are essential to maximize the benefits of online health education in China.
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Educación en Salud , Alfabetización en Salud , Internet , China , Humanos , Educación en Salud/organización & administración , Educación a Distancia/organización & administración , Educación a Distancia/métodos , Brecha DigitalRESUMEN
The chemical constituents of Draconis Sanguis were preliminarily studied by macroporous resin, silica gel, dextran gel, and high-performance liquid chromatography. One retro-dihydrochalcone, four flavonoids, and one stilbene were isolated. Their chemical structures were identified as 4-hydroxy-2,6-dimethoxy-3-methyldihydrochalcone(1), 4'-hydroxy-5,7-dimethoxy-8-methylflavan(2), 7-hydroxy-4',5-dimethoxyflavan(3),(2S)-7-hydroxy-5-methoxy-6-methylflavan(4),(2S)-7-hydroxy-5-methoxyflavan(5), and pterostilbene(6) by modern spectroscopy, physicochemical properties, and literature comparison. Compound 1 was a new compound. Compounds 2 and 6 were first found in the Arecaceae family. Compound 5 had the potential to prevent and treat diabetic kidney disease.
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Arecaceae , Diabetes Mellitus , Nefropatías Diabéticas , Medicamentos Herbarios Chinos , Nefropatías Diabéticas/tratamiento farmacológico , Nefropatías Diabéticas/prevención & control , Flavonoides/análisis , Medicamentos Herbarios Chinos/química , Cromatografía Líquida de Alta Presión/métodosRESUMEN
Long non-coding RNAs (lncRNAs) regulate neurological damage in cerebral ischemia-reperfusion injury (CIRI). This study aimed to investigate the biological roles of lncRNA CEBPA-AS1 in CIRI. Middle cerebral artery occlusion and ischemia-reperfusion injury (MCAO/IR) rat model and oxygen-glucose deprivation and reoxygenation (OGD/R) cell lines were generated; the expression of CEBPA-AS1 was evaluated by qRT-PCR. The effects of CEBPA-AS1 on cell apoptosis and nerve damage were examined. The downstream microRNA (miRNA) and mRNA of CEBPA-AS1 were predicted and verified. We found that overexpression of CEBPA-AS1 could attenuate MCAO/IR-induced nerve damage and neuronal apoptosis in the rat model. Knockdown of CEBPA-AS1 aggravated cell apoptosis and enhanced the production of LDH and MDA in the OGD/R cells. Upon examining the molecular mechanisms, we found that CEBPA-AS1 stimulated APPL1 expression by combining with miR-340-5p, thereby regulating the APPL1/LKB1/AMPK pathway. In the rescue experiments, CEBPA-AS1 overexpression was found to attenuate OGD/R-induced cell apoptosis and MCAO/IR induced nerve damage, while miR-340-5p reversed these effects of CEBPA-AS1. In conclusion, CEBPA-AS1 could decrease CIRI by sponging miR-340-5, regulating the APPL1/LKB1/AMPK pathway.
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Quinasas de la Proteína-Quinasa Activada por el AMP/biosíntesis , Proteínas Quinasas Activadas por AMP/biosíntesis , Proteínas Adaptadoras Transductoras de Señales/biosíntesis , Trastornos Cerebrovasculares/metabolismo , MicroARNs/biosíntesis , Proteínas del Tejido Nervioso/biosíntesis , ARN Largo no Codificante/biosíntesis , Daño por Reperfusión/metabolismo , Transducción de Señal , Quinasas de la Proteína-Quinasa Activada por el AMP/genética , Proteínas Quinasas Activadas por AMP/genética , Proteínas Adaptadoras Transductoras de Señales/genética , Animales , Apoptosis , Trastornos Cerebrovasculares/genética , Trastornos Cerebrovasculares/patología , Modelos Animales de Enfermedad , Regulación de la Expresión Génica , MicroARNs/genética , Proteínas del Tejido Nervioso/genética , ARN Largo no Codificante/genética , Ratas , Ratas Sprague-Dawley , Daño por Reperfusión/genética , Daño por Reperfusión/patologíaRESUMEN
Candidiasis is one of the most important fungal diseases and generally refers to diseases of the skin or mucosal tissues caused by Candida species. Candida glabrata is an opportunistic human fungal pathogen. Infection with C. glabrata has significantly increased due to innate antifungal drug tolerance and the ability to adhere to mucocutaneous surfaces. Spt-Ada-Gcn5 acetyltransferase complex contains two different post-translational modifications, histone acetylation (HAT) module and deubiquitination (DUB) module, which are decisive in gene regulation and highly conserved in eukaryotes. Previous research in our laboratory found that the HAT module ADA2 could regulate C. glabrata oxidative stress tolerance, drug tolerance, cell wall integrity, and virulence. However, the roles of the DUB module that is comprised of UBP8, SGF11, SGF73, and SUS1 genes in those phenotypes are not yet understood. In this study, we found that DUB module genes UBP8, SGF11, and SUS1, but not SGF73 positively regulate histone H2B DUB. Furthermore, ubp8, sgf11, and sus1 mutants exhibited decreased biofilm formation and sensitivity to cell wall-perturbing agent sodium dodecyl sulfate and antifungal drug amphotericin B. In addition, the sgf73 mutant showed increased biofilm formation but was susceptible to oxidative stresses, antifungal drugs, and cell wall perturbing agents. The ubp8, sgf11, and sus1 mutants showed marginal hypovirulence, whereas the sgf73 mutant exhibited virulence similar to the wild type in a murine systemic infection model. In conclusion, the C. glabrata DUB module plays distinct roles in H2B ubiquitination, oxidative stress response, biofilm formation, cell wall integrity, and drug tolerance, but exhibits minor roles in virulence.
In this study, we found that the deubiquitination (DUB) module of the Spt-Ada-Gcn5 acetyltransferase complex is involved in H2B DUB, oxidative stress response, biofilm formation, cell wall integrity, and drug tolerance in the human fungal pathogen Candida glabrata. The multiple functions controlled by the DUB module exhibit conserved and divergent functions between Saccharomyces cerevisiae, C. albicans, and C. glabrata.
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Candida glabrata , Proteínas de Saccharomyces cerevisiae , Humanos , Animales , Ratones , Candida glabrata/genética , Transactivadores/metabolismo , Proteínas de Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/metabolismo , Saccharomyces cerevisiae/genética , Antifúngicos/farmacología , Antifúngicos/metabolismo , Histona Acetiltransferasas/genética , Histonas/metabolismo , Biopelículas , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismoRESUMEN
We report a base-promoted cyclization with indene-dienes as two carbon building blocks toward diverse spirocyclic indene scaffolds including hexacyclic spiroindenes bearing benzo pyran motifs and pentacyclic spiroindenes containing oxindole units in high yields with excellent diastereoselectivities.
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The regioselective [3 + 2] cycloaddition reaction of 2-benzylidene-1-indenones with functional olefins was established with DABCO as a base under mild conditions. Using this approach, a series of diversely substituted indanone-fused cyclopentane polycycles with highly crowded multiple substituents were synthesized in high yields.
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Adding small molecular plasticizers is the most common route to tailor the stretchability of poly(vinyl alcohol) (PVA). However, how the plasticization along with the nature of the plasticizer governs the structural homogeneity during stretching remains an open question to answer. Herein, two representative plasticizers, glycerol (GLY) and water, are chosen to endow the PVA films with ductility. It is found that large strain cavitations cause obvious stress whitening in the PVA/H2 O films; on the contrary, most of the PVA/GLY films maintain transparent undergoing tensile deformation. Through a combination of experimental inspections and molecular dynamic simulation, it is revealed that partial water molecules that behave as free water will aggregate into microdomains, which serve as mechanical defects responsible for yielding voids. Whereas, the GLY plasticizer homogeneously disperses at a molecular level and interacts with PVA chains through strong hydrogen bonds. More interestingly, it is illustrated that the dispersion and bound states of plasticizers are closely related to the mechanical character of the plasticized PVA films. These findings offer new insight into the working mechanism of plasticization on the structural stability during stretching, and guide the design of PVA/plasticizer system to obtain excellent comprehensive mechanics.
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Alcohol Polivinílico , Agua , Alcohol Polivinílico/química , Agua/química , Plastificantes/química , Glicerol , Resistencia a la TracciónRESUMEN
BACKGROUND AND AIM: Radiation therapy (RT) is a crucial modality for the local control of esophageal cancer (EC), but the effect of RT on the development of secondary thoracic malignancies is still unclear. This study aims to identify the association between RT for the treatment of primary EC and subsequent secondary thoracic cancer (STC). METHODS: The primary EC patients were retrieved from the Surveillance, Epidemiology, and End Results (SEER) database. Fine-Gray competing risk regression and standardized incidence ratio (SIR) were used to evaluate the radiotherapy-associated cancer risk. Overall survival (OS) was compared by Kaplan-Meier analysis. RESULTS: A total of 40 255 EC patients from the SEER database were identified, of which 17 055 patients (42.37%) did not receive radiotherapy (NRT) and 23 200 patients (57.63%) had been treated with RT. After 12 months of latency, 162 patients (0.95%) in the NRT group and 272 patients (1.17%) in the RT group developed STC. The incidences of the RT group were significantly higher than the NRT group. Patients who have primary EC were at an increased risk of developing STC (SIR = 1.79, 95% CI: 1.63-1.96). The SIR of STC was 1.37 (95% CI: 1.16-1.60) in the NRT group and 2.10 (95% CI: 1.87-2.34) in the RT group. The OS of STC patients in the RT group was significantly lower than the NRT group (P = 0.006). CONCLUSION: The RT for primary EC was associated with higher risks of developing STC than patients unexposed to radiotherapy. The EC patients treated with RT, especially young patients, require long-term monitoring of the risk of STC.
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Neoplasias Esofágicas , Neoplasias Primarias Secundarias , Humanos , Pronóstico , Neoplasias Primarias Secundarias/epidemiología , Neoplasias Primarias Secundarias/etiología , Neoplasias Esofágicas/epidemiología , Neoplasias Esofágicas/etiología , Neoplasias Esofágicas/radioterapia , Riesgo , Incidencia , Programa de VERFRESUMEN
Renal fibrosis is a common pathological feature of chronic kidney disease (CKD) with various etiologies, which seriously affects the structure and function of the kidney. Pregnane X receptor (PXR) is a member of the nuclear receptor superfamily and plays a critical role in regulating the genes related to xenobiotic and endobiotic metabolism in mammals. Previous studies show that PXR is expressed in the kidney and has protective effect against acute kidney injury (AKI). In this study, we investigated the role of PXR in CKD. Adenine diet-induced CKD (AD) model was established in wild-type and PXR humanized (hPXR) mice, respectively, which were treated with pregnenolone-16α-carbonitrile (PCN, 50 mg/kg, twice a week for 4 weeks) or rifampicin (RIF, 10 mg·kg-1·d-1, for 4 weeks). We showed that both PCN and RIF, which activated mouse and human PXR, respectively, improved renal function and attenuated renal fibrosis in the two types of AD mice. In addition, PCN treatment also alleviated renal fibrosis in unilateral ureter obstruction (UUO) mice. On the contrary, PXR gene deficiency exacerbated renal dysfunction and fibrosis in both adenine- and UUO-induced CKD mice. We found that PCN treatment suppressed the expression of the profibrotic Wnt7a and ß-catenin in AD mice and in cultured mouse renal tubular epithelial cells treated with TGFß1 in vitro. We demonstrated that PXR was colocalized and interacted with p53 in the nuclei of tubular epithelial cells. Overexpression of p53 increased the expression of Wnt7a, ß-catenin and its downstream gene fibronectin. We further revealed that p53 bound to the promoter of Wnt7a gene to increase its transcription and ß-catenin activation, leading to increased expression of the downstream profibrotic genes, which was inhibited by PXR. Taken together, PXR activation alleviates renal fibrosis in mice via interacting with p53 and inhibiting the Wnt7a/ß-catenin signaling pathway.
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Receptor X de Pregnano , Insuficiencia Renal Crónica , Vía de Señalización Wnt , Animales , Humanos , Ratones , beta Catenina/metabolismo , Fibrosis , Mamíferos/metabolismo , Receptor X de Pregnano/metabolismo , Receptores de Esteroides/genética , Receptores de Esteroides/metabolismo , Insuficiencia Renal Crónica/inducido químicamente , Insuficiencia Renal Crónica/tratamiento farmacológico , Transducción de Señal , Proteína p53 Supresora de Tumor/metabolismo , Rifampin/farmacologíaRESUMEN
To explore the utility of transcranial Doppler (TCD) findings when assessing bypass patency in patients with Moyamoya disease (MMD). Computed tomography angiography (CTA) and TCD sonography (TCDS) were performed before and after surgery to evaluate bypass patency. The peak systolic flow velocity (PSV) of the superficial temporal artery (STA) and the pulsatility index (PI) were compared between the groups that achieved patency and not, and receiver operating characteristic (ROC) curve analyses were used to define the TCDS criteria revealing patency. This study included 35 hemispheres (15 women; mean age 47 years) with Moyamoya disease who underwent STA-middle carotid artery bypass in our institution between January 2022 and October 2022. The PSV first increased on postoperative days 4-5 and then decreased on postoperative days 6-7 and 7-8. Patients with transient neurological diseases (TNDs), compared to those without, evidenced a significantly lower PSV value (P < 0.05). Compared with the non-patency group, the PSV was higher (P < 0.001) in the patency group. The cutoff values reflecting patency with good sensitivity and specificity were PSV > 49.00; PSV ratio (postoperative/preoperative) > 1.218; PSV ratio (operation side/contralateral side) > 1.082; and PSV ratio (adjusted) > 1.202. In the patency group, the PSV and PI significantly increased (P < 0.001) and decreased (P < 0.001) respectively. Bypass patency can be noninvasively and accurately evaluated via TCDS, affording an objective basis for assessment of the effect of revascularization surgery on patients with MMD.
Asunto(s)
Angiografía por Tomografía Computarizada , Enfermedad de Moyamoya , Humanos , Femenino , Persona de Mediana Edad , Enfermedad de Moyamoya/diagnóstico por imagen , Enfermedad de Moyamoya/cirugía , Ultrasonografía Doppler Transcraneal , AngiografíaRESUMEN
Significant shock of climate change on crop yield will challenge the performance of bio-crop on substituting fossil energy to mitigate climate change. Taking cassava-to-ethanol system in Guangxi Province of South China as an example, we coupled a random forest (RF) model with 10 Global climate models (GCMs) outputs to predict the future cassava yields. Subsequently, the net energy value (NEV) and greenhouse gas (GHG) emissions of the cassava-to-ethanol system across varied topographies are assessed using a life cycle analysis. We demonstrate that the abrupt increases in temperatures are the primary contributors to declining yields. Notably, cassava yields in hilly regions decline more than those in plains and display greater variability among concentration pathway scenarios over time. Future NEV and GHG performance of cassava-to-ethanol will undergo significant decreases over time, especially within the high concentration pathway scenario (NEV decrease 28%, GHG increase 3.4% from 2006 to 2100). The performance reductions in hilly area are exacerbated by more harvest loss and labor and material inputs during the "field-to-wheel", negating its energy advantage over fossil fuels. Therefore, adopting a lower concentration pathway and favoring plantation in plains could maintain cassava-to-ethanol as a viable climate mitigation strategy. Our research also advances the methodological approach to climate change adaptation within the domain of life cycle assessment.
Asunto(s)
Gases de Efecto Invernadero , Manihot , Efecto Invernadero , Etanol , Cambio Climático , China , VerdurasRESUMEN
Natural products play a key role in innovative drug discovery. To explore the potential application of natural products and their analogues in pharmacology, total synthesis is a key tool that provides natural product candidates and synthetic analogues for drug development and potential clinical trials. Deconstructive synthesis, namely building new, challenging structures through bond cleavage of easily accessible moieties, has emerged as a useful design principle in synthesizing bioactive natural products. Divergent synthesis, namely synthesizing many natural products from a common intermediate, can improve the efficiency of chemical synthesis and generate libraries of molecules with unprecedented structural diversity. In this review, we will firstly introduce five recent and excellent examples of deconstructive and divergent syntheses of natural products (2021-2023). Then, we will summarize our previous work on the deconstructive and divergent synthesis of natural products to demonstrate the high efficiency and simplicity of these two strategies in the field of total synthesis.