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BACKGROUND: The comprehensive quantitative and comparative risk data of drug-induced erectile dysfunction (ED) are still lacking, and this study aims to supplement this information. RESEARCH DESIGN AND METHODS: We reviewed all the ED reports in the FDA Adverse Event Reporting System (FAERS) database from 2004 to 2023 and summarized a potential ED culprit-drug list and its corresponding reporting frequency. The reporting odds ratio (ROR) method was used to conduct disproportionality analysis. RESULTS: A total of 20,098 ED reports were retrieved from the FAERS database, which recorded 734 different ED culprit-drugs, involving 74 drug classes. Finasteride was the drug with the highest reporting frequency, and urologicals was the drug class with the highest reporting frequency. In disproportionality analysis, 209 drugs with positive signals showed a close relationship with ED occurrence, among which finasteride was the drug with the highest signal strength. Among 209 drugs with positive signals, 27 were compound preparations, and the risk level of compound preparations was usually higher than their single active ingredient. CONCLUSIONS: Our study integrated quantitative and comparative ED risk data of 734 drugs by using the FAERS database, which can provide reference information for regulators, medical personnel, and others involved in drug management and use.
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RAB3B is essential for the transportation and secretion within cells. Its increased expression is linked to the development and progression of various malignancies. However, understanding of RAB3B's involvement in carcinogenesis is mostly limited to specific cancer subtypes. Hence, exploring RAB3B's regulatory roles and molecular mechanisms through comprehensive cancer datasets might offer innovative approaches for managing clinical cancer. To examine the potential involvement of RAB3B in the development of cancer, we analyzed data from various sources including The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression Project (GTEx), cBioPortal, HPA, UALCAN, and tissue microarray (TAM). Using bioinformatics techniques, we examined the correlation between RAB3B expression and prognosis, tumor heterogeneity, methylation modifications, and immune microenvironment across different cancer types. Our findings indicate that elevated RAB3B expression can independently predict prognosis in many tumors and has moderate accuracy for diagnosing most cancers. In most cancer types, we identified RAB3B mutations that showed a significant correlation with tumor mutational burden (TMB), mutant-allele tumor heterogeneity (MATH), and microsatellite instability (MSI). Abnormal DNA methylation patterns were also observed in most cancers compared to normal tissues. Additionally, we found significant correlations between RAB3B expression, immune cell infiltration, and immune scores across various cancers. Through pan-cancer analysis, we observed significant differences in RAB3B expression levels between tumors and normal tissues, making it a potential primary factor for cancer diagnosis and prognosis. The IHC results revealed that the expression of RAB3B in six types of tumors was consistent with the results of the pan-cancer analysis of the database. Furthermore, RAB3B showed potential associations with tumor heterogeneity and immunity. Thus, RAB3B can be utilized as an auxiliary diagnostic marker for early tumor detection and a prognostic biomarker for various tumor types.
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Biomarcadores Tumorais , Metilação de DNA , Regulação Neoplásica da Expressão Gênica , Neoplasias , Microambiente Tumoral , Proteínas rab3 de Ligação ao GTP , Humanos , Biomarcadores Tumorais/genética , Biologia Computacional/métodos , Mutação , Neoplasias/genética , Neoplasias/imunologia , Neoplasias/diagnóstico , Neoplasias/patologia , Prognóstico , Proteínas rab3 de Ligação ao GTP/genética , Proteínas rab3 de Ligação ao GTP/metabolismo , Microambiente Tumoral/imunologia , Microambiente Tumoral/genéticaRESUMO
A multifunction processor for a broadband signal based on the active mode-locking optoelectronic oscillator (OEO) is proposed and experimentally demonstrated. The central frequency down-conversion and frequency spectrum convolution of the target broadband signal (TBS) are realized by just tuning the wavelength of the optical carrier or by the time domain product, respectively. To achieve the central frequency down-conversion of the TBS, an optical tunable delay line (OTDL) is adopted to match the delay time of the OEO loop with the repetition period of the TBS. Then the spectrum convolution of the TBS is produced by just injecting a lower frequency signal consistent with the free spectral range (FSR) of the OEO loop. Moreover, the frequency convolution repetition is also greatly increased by harmonic mode-locking injection. The equivalent bandwidth of the TBS is enlarged by â¼50 times, benefiting from the frequency convolution. The central frequency conversion flexibility and the bandwidth compatibility are also discussed in detail. This work provides a multifunction processor system and may have potential usage in multifunctional integrated radar systems.
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Purpose: Premenstrual syndrome (PMS) is a cyclical psychosomatic disorder prevalent among women of reproductive age. However, research on the potential impact of PMS on routine nursing schedules and activities is limited. This study aims to identify the prevalence of PMS among female nursing staff and to examine the relationship between PMS and missed nursing care (MNC). Method: Between November 1, 2022, and April 30, 2023, this study was conducted among female nursing staff working in nine inpatient departments at Sun Yat-sen University Cancer Center. This study used a cross-sectional design. The participants were recruited through convenience sampling. Data were collected using the standardized Menstrual Distress Questionnaire, the Oncology Missed Nursing Care self-rating scale, and a sociodemographic questionnaire. One-way analysis of variance, Fisher's least significant difference test for post-hoc comparisons, and Spearman's correlation coefficient were utilized for data analysis. A trend test was also performed to explore patterns in the severity of PMS and MNC over time. Results: We collected a total of 224 questionnaires, with 154 (68.7%) female nursing staff reporting PMS. The most common symptoms were low back pain (91.1%), abdominal discomfort (90.6%), cold hands and feet (87.1%), and lethargy (87.1%). Moreover, 91.5% of the 224 female nursing staff reported at least one MNC activity. The nursing activities most frequently missed or left incomplete were liquid intake and output monitoring as ordered (43.3%), medication administration within 30 min before or after the scheduled time (43.3%), and electrocardiogram monitoring as ordered (42.9%). "Abdominal discomfort" from the Menstrual Distress Questionnaire was significantly correlated with the majority of MNC activities (p < 0.001). Conclusions: This study provides evidence for a strong association between PMS and MNC among female nursing staff, suggesting that administrators should take the premenstrual conditions of female nursing staff into consideration. It is necessary to provide appropriate understanding and support to mitigate the impact on patient care and safety.
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N6-Methyladenosine (m6A) is the most abundant chemical modification occurring on eukaryotic mRNAs, and has been reported to be involved in almost all stages of mRNA metabolism. The distribution of m6A sites is notably asymmetric along mRNAs, with a strong preference toward the 3' terminus of the transcript. How m6A regional preference is shaped remains incompletely understood. In this study, by performing m6A-seq on chromatin-associated RNAs, we found that m6A regional preference arises during transcription. Nucleosome occupancy is remarkedly increased in the region downstream of m6A sites, suggesting an intricate interplay between m6A methylation and nucleosome-mediated transcriptional dynamics. Notably, we found a remarkable slowdown of Pol-II movement around m6A sites. In addition, inhibiting Pol-II movement increases nearby m6A methylation levels. By analyzing massively parallel assays for m6A, we found that RNA secondary structures inhibit m6A methylation. Remarkably, the m6A sites associated with Pol-II pausing tend to be embedded within RNA secondary structures. These results suggest that Pol-II pausing could affect the accessibility of m6A motifs to the methyltransferase complex and subsequent m6A methylation by mediating RNA secondary structure. Overall, our study reveals a crucial role of transcriptional dynamics in the formation of m6A regional preference.
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Adenosina , Adenosina/análogos & derivados , RNA Polimerase II , RNA Mensageiro , Transcrição Gênica , Adenosina/metabolismo , Metilação , RNA Mensageiro/metabolismo , RNA Mensageiro/genética , RNA Polimerase II/metabolismo , Humanos , Conformação de Ácido Nucleico , Nucleossomos/metabolismo , Nucleossomos/genética , Metiltransferases/metabolismo , Metiltransferases/genética , Cromatina/metabolismo , Cromatina/genética , Cromatina/químicaRESUMO
INTRODUCTION: The aim of this work is to evaluate the accuracy of the Barrett Universal II (BU II), Emmetropia verifying optical (EVO) 2.0, Haigis, Hoffer Q, Hoffer QST (Savini/Taroni) (HQST), Holladay 1, Kane, Ladas Super, Sanders-Retzlaff-Kraff/theoretical (SRK/T), and T2 intraocular lens (IOL) power formulas for calculating spherical equivalent (SE) of toric IOL. METHODS: This study enrolled consecutive patients who underwent phacoemulsification and toric IOL implantation at the Eye Hospital of Wenzhou Medical University in Hangzhou from 2015 to 2022. We compared the new-generation formulas with Gaussian optics-based standard formulas, and calculated the mean absolute error (MAE), median absolute error (MedAE), and percentage of eyes within ± 0.25 diopter (D), ± 0.50 D, ± 0.75 D and ± 1.00 D of the target refraction. Subgroup analyses were conducted based on the anterior chamber depth (ACD), keratometry (K), and toricity (T). RESULTS: A total of 207 eyes of 207 patients were included in this study. Overall, the Kane and EVO2.0 formulas demonstrated the lowest MedAEs. The EVO2.0 formula exhibited the highest percentage of eyes within ± 0.50 D, ± 0.75 D, ± 1.00 D. Moreover, the EVO2.0 formula showed the lowest MedAE for flat K subgroup, the highest percentage of eyes within ± 0.50 D, ± 1.00 D for shallow ACD subgroup, the highest percentage of eyes within ± 0.75 D for regular ACD, flat K, T2-T3, T4-T5 subgroups. The Kane and formula performed the lowest MedAE in the T4-T5 subgroup. CONCLUSIONS: Application of the Kane and EVO2.0 formulas significantly improved the prediction of postoperative SE outcome for toric IOL compared to the other formulas.
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Herein, activated red mud particles are used as adsorbents for phosphorus adsorption. HCl solutions with different concentrations and deionized water are employed for desorption tests, and the desorption mechanism under the following optimal conditions is investigated: HCl concentration = 0.2 mol/L, desorbent dosage = 0.15 L/g, desorption temperature = 35 °C, and desorption time = 12 h. Under these conditions, the phosphate desorption rate and amount reach 99.11% and 11.29 mg/g, respectively. Notably, the Langmuir isothermal and pseudo-second-order kinetic linear models exhibit consistent results: monomolecular-layer surface desorption is dominant, and chemical desorption limits the rate of surface desorption. Thermodynamic analysis indicates that phosphorus desorption by the desorbents is spontaneous and that high temperatures promote such desorption. Moreover, an intraparticle diffusion model demonstrates that the removal of phosphorus in the form of precipitation from the surface of an activated hematite particle adsorbent primarily occurs via a chemical reaction, and surface micromorphological analysis indicates that desorption is primarily accompanied by Ca dissolution, followed by Al and Fe dissolutions. The desorbents react with the active elements in red mud, and the vibrations of the [SiO4]4- functional groups of calcium-iron garnet and calcite or aragonite disappear. Further, in Fourier-transform infrared spectra, the intensities of the peaks corresponding to the PO43- group considerably decrease. Thus, desorption primarily involves monomolecular-layer chemical desorption.
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Red mud (RM), a bauxite residue, contains hazardous radioactive wastes and alkaline material and poses severe surface water and groundwater contamination risks, necessitating recycling. Pretreated RM can be used to make adsorbents for water treatment. However, its performance is affected by many factors, resulting in a nonlinear correlation and coupling relationship. This study aimed to identify the best formula for an RM adsorbent using a mathematical model that examines the relationship between 11 formulation types (e.g., pore-assisting agent, component modifier, and external binder) and 9 properties (e.g., specific surface area, wetting angle, and Zeta potential). This model was built using a back-propagation neural network (BP) based on single-factor experimental data and orthogonal experimental data. The model trained and predicted the established network structure to obtain the optimal adsorbent formula. The RM particle adsorbents had a pH of 10.16, specific surface area (BET) of 48.92 m2·g-1, pore volume of 2.10 cm3·g-1, compressive strength (ST) of 1.12 KPa, and 24 h immersion pulverization rate (ηm) of 3.72%. In the removal of total phosphorus in flotation tailings backwater, it exhibited a good adsorption capacity (Q) and total phosphorous removal rate (η) of 48.63 mg·g-1 and 95.13%, respectively.
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Colorectal cancer (CRC) is a worldwide health concern. Chronic inflammation is a risk factor for CRC, and interleukin-6 (IL-6) plays a pivotal role in this process. Arginine-specific mono-ADP-ribosyltransferase-1 (ART1) positively regulates inflammatory cytokines. ART1 knockdown reduces the level of glycoprotein 130 (gp130), a key transducer in the IL-6 signalling pathway. However, the relationship between ART1 and IL-6 and the resulting effects on IL-6-induced proliferation in CRC cells remain unclear. The aims of this study were to investigate the effects of ART1 knockdown on IL-6-induced cell proliferation in vitro and use an in vivo murine model to observe the growth of transplanted tumours. The results showed that compared with the control, ART1-sh cancer cells induced by IL-6 exhibited reduced viability, a lower rate of colony formation, less DNA synthesis, decreased protein levels of gp130, c-Myc, cyclin D1, Bcl-xL, and a reduced p-STAT3/STAT3 ratio (P < 0.05). Moreover, mice transplanted with ART1-sh CT26 cells that had high levels of IL-6 displayed tumours with smaller volumes (P < 0.05). ART1 and gp130 were colocalized in CT26, LoVo and HCT116 cells, and their expression was positively correlated in human CRC tissues. Overall, ART1 may serve as a promising regulatory factor for IL-6 signalling and a potential therapeutic target for human CRC.
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Neoplasias Colorretais , Interleucina-6 , Humanos , Animais , Camundongos , Interleucina-6/genética , ADP Ribose Transferases/genética , ADP Ribose Transferases/metabolismo , Receptor gp130 de Citocina/genética , Linhagem Celular Tumoral , Poli(ADP-Ribose) Polimerases/genética , Proliferação de Células , Neoplasias Colorretais/patologia , Proteínas Ligadas por GPI/metabolismoRESUMO
OBJECTIVE: Various psychological interventions have been demonstrated to be effective at preventing anxiety and depression symptoms in patients with gastrointestinal (GI) cancer. However, it remains unclear which intervention is the best option. This study aimed to evaluate the impact of various psychological interventions on anxiety and depression in symptomatic patients with GI cancer. METHODS: The PubMed, Cochrane Library, Embase, CNKI, WanFang Data, and VIP databases were systematically searched from inception to June 2023 to identify randomized controlled trials (RCTs). The primary outcomes were anxiety and depression levels. Two reviewers independently selected the studies, extracted the data based on prespecified criteria, and evaluated the risk of bias using the Cochrane Collaboration risk of bias tool. Stata 14.0 was used to conduct network meta-analysis. RESULTS: Thirty-two RCTs (2453 patients) involving 9 psychological interventions were included. The results of the network meta-analysis showed that cognitive-behavioral therapy (CBT; mean difference [MD] = -4.98, 95% CI (-7.04, -2.93), relaxation therapy (MD = -4.39, 95% CI (-7.90, -0.88), reminiscence therapy (MD = -5.01, 95% CI (-8.20, -1.81)), and narrative nursing (MD = -4.89, 95% CI (-8.54, -1.23)) significantly reduced anxiety levels, and CBT (MD = -2.15, 95% CI (-4.28, -0.02), reminiscence therapy (MD = -7.20, 95% CI (-10.48, -3.91), and narrative nursing (MD = -7.20, 95% CI (-10.48, -3.91)) significantly reduced depression levels in patients with GI cancer compared with conventional nursing care. CONCLUSION: The findings of this network meta-analysis revealed that CBT, reminiscence therapy and narrative nursing can be actively considered as part of sequential therapy to reduce anxiety and depression levels in patients with GI cancer.
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Ansiedade , Depressão , Neoplasias Gastrointestinais , Metanálise em Rede , Psicoterapia , Humanos , Neoplasias Gastrointestinais/psicologia , Neoplasias Gastrointestinais/complicações , Neoplasias Gastrointestinais/terapia , Depressão/terapia , Depressão/psicologia , Ansiedade/terapia , Ansiedade/psicologia , Psicoterapia/métodos , Ensaios Clínicos Controlados Aleatórios como Assunto , Terapia Cognitivo-Comportamental/métodosRESUMO
Burkitt lymphoma is a highly invasive non-Hodgkin lymphoma. Sporadic Burkitt's lymphoma is commonly found in the abdomen. However, Burkitt lymphoma infiltrating the uterus is uncommon in occurrence. We report the results of 18F-FDG PET/CT examination of a 36-year-old woman. The report indicates that in addition to the strong uptake of FDG imaging agent in the uterus, bilateral cervical and abdominal lymph nodes also have strong activity. At the same time, it was also found that bilateral small breast nodules, sacral canal and multiple bones in the whole body showed a radiation uptake pattern similar to that of the uterus. 18F-FDG PET/CT imaging can help determine the extent of the disease and the affected body area, which is helpful to guide the treatment decision. This case report shows the application of 18F-FDG PET/CT imaging in the diagnosis, staging and post-treatment evaluation of Burkitt lymphoma of the uterus. It provides very useful information for clinicians and helps to improve the accuracy of diagnosis and treatment effect.
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AIM: To investigate the efficacy of a new visual acuity (VA) screening method, the baby vision test for young children. METHODS: A total 105 eyes of 65 children aged 2-8y were included in the study. Acuity testing was conducted using a standardized recognition acuity chart (Snellen visual chart: at 3 m) and the baby vision model assessment. The baby vision device includes a screen, a near infrared camera and a computer. Children were seated at a measured distance of 33-40 cm from a display for testing. VA was estimated according to the highest resolution the children could follow. Decimal VA data were converted to logarithm of the minimum angle of resolution (logMAR) for statistical analysis. The VA results for each child were recorded and analyzed for consistency. RESULTS: The mean VA measured using the Snellen visual chart was 0.62±0.32, and that assessed using the baby vision test was 0.66±0.27. The 95% limit of agreement was -0.609 to 0.695, with 95.2% (100/105) plots within the 95% limits of agreement. VA values of the baby vision test were significantly correlated with those of the Snellen chart (R=0.274, P=0.005). CONCLUSION: The baby vision test can be used as a relatively reliable method for estimating VA in young children. This new acuity assessment might be a valid predictor of optotype-measured acuity later in preverbal children.
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The current review was undertaken to collate data on Gpx4 inhibitors and the regulatory proteins related to Gpx4. Gpx4 plays an essential role in ferroptosis; it can be used to determine the Gpx4 as an indicator for determining tumor occurrence and as a means of treating cancer. Although there is no market for Gpx4 inhibitors, many researchers have conducted extensive research, and some compounds have entered clinical research. This article summarizes all papers related to Gpx4; hope this review can provide some new insights and ideas for researchers aiming to develop efficient and low-- toxicity Gpx4 inhibitors and provide some new ideas for cancer treatment.
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Thyroid hormone receptor interactor 6 (TRIP6) it is an adaptor protein belonging to the zyxin family of LIM proteins, participating in signaling events through interactions with various molecules. Despite this, TRIP6's role in colorectal cancer (CRC), particularly its correlation with glucose metabolism and immune cell infiltration, remains unclear. Through the TCGA and GEO databases, we obtained RNA sequencing data to facilitate our in-depth study and analysis of TRIP6 expression. To investigate the prognostic value of TRIP6 in CRC, we also used univariate Cox regression analysis. In addition, this study also covered a series of analyses, including clinicopathological analysis, functional enrichment analysis, glycolysis correlation analysis, immunoinfiltration analysis, immune checkpoint analysis, and angiogenesis correlation analysis, to gain a comprehensive and in-depth understanding of this biological phenomenon. It has been found that TRIP6 expression is significantly upregulated in CRC and correlates with the stage of the disease. Its overexpression portends a worse survival time. Functional enrichment analysis reveals that TRIP6 is associated with focal adhesion and glycolysis. Mechanistically, TRIP6 appears to exert its tumorigenic effect by regulating the glycolysis-related gene GPI. A higher level of expression of TRIP6 is associated with an increase in the number of iDC immune cells and a decrease in the number of Th1 immune cells. Also, TRIP6 may promote angiogenesis in tumor cells by promoting the expression of JAG2. Our study uncovers the upregulation of TRIP6 in CRC, illuminating its prognostic and diagnostic value within this context. Furthermore, we examine the relationship between TRIP6 expression levels, glycolysis, angiogenesis and immune cell infiltration. This underscores its potential as a biomarker for CRC treatment and as a therapeutic target.
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Proteínas Adaptadoras de Transdução de Sinal , Neoplasias Colorretais , Proteínas com Domínio LIM , Fatores de Transcrição , Humanos , Proteínas Adaptadoras de Transdução de Sinal/genética , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Glicólise , Proteínas com Domínio LIM/genética , Proteínas com Domínio LIM/metabolismo , Complexo de Endopeptidases do Proteassoma/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismoRESUMO
OBJECTIVE: Spindle pole body component 25 (SPC25) is an important cyclin involved in chromosome segregation and spindle dynamics regulation during mitosis. However, the role of SPC25 in lung adenocarcinoma (LAUD) is unclear. MATERIALS AND METHODS: The differential expression of SPC25 in tumor samples and normal samples was analyzed using TIMER, TCGA, GEO databases, and the correlation between its expression and clinicopathological features and prognosis in LUAD patients. Biological pathways that may be enriched by SPC25 were analyzed using GSEA. In vitro cell experiments were used to evaluate the effect of knocking down SPC25 expression on LUAD cells. Correlation analysis and differential analysis were used to assess the association of SPC25 expression with genes related to cell cycle, glycolysis, and ferroptosis. A ceRNA network involving SPC25 was constructed using multiple database analyses. RESULTS: SPC25 was highly expressed in LUAD, and its expression level could guide staging and predict prognosis. GSEA found that high expression of SPC25 involved multiple cell cycles and glycolytic pathways. Knocking down SPC25 expression significantly affected the proliferation, migration and apoptosis of LUAD cells. Abnormal SPC25 expression levels can affect cell cycle progression, glycolytic ability and ferroptosis regulation. A ceRNA network containing SPC25, SNHG15/hsa-miR-451a/SPC25, was successfully predicted and constructed. CONCLUSIONS: Our findings reveal the association of up-regulation of SPC25 in LUAD and its expression with clinical features, prognosis prediction, proliferation migration, cell cycle, glycolysis, ferroptosis, and ceRNA networks. Our results indicate that SPC25 can be used as a biomarker in LUAD therapy and a target for therapeutic intervention.
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Adenocarcinoma de Pulmão , Ferroptose , Neoplasias Pulmonares , Humanos , Prognóstico , RNA Endógeno Competitivo , Ferroptose/genética , Corpos Polares do Fuso , Adenocarcinoma de Pulmão/genética , Mitose , Neoplasias Pulmonares/genética , Proteínas Associadas aos MicrotúbulosRESUMO
PURPOSE: To determine the clinical efficacy of different respiratory training interventions on swallowing function in patients with swallowing disorders through the systematic review. METHODS: We reviewed the literature regarding the application of respiratory training therapy in patients with swallowing disorders, followed by a PRISMA search of published literature in five databases (PubMed, Web of Science, The Cochrane Library, CINAHL and EMBASE) in December 2022. Two reviewers performed study selection, quality evaluation, and risk of bias, followed by data extraction and detailed analysis. RESULTS: A total of six randomized controlled studies with a total sample size of 193 cases were included. Respiratory training improved swallowing safety (PAS (n = 151, SMD = 0.69, 95% CI - 1.11 to - 0.26, I2 = 36, p < 0.001)) and swallowing efficiency [residual (n = 63, SMD = 1.67, 95% CI - 2.26 to - 1.09, I2 = 23%, p < 0.001)] compared to control groups. The results of the qualitative analysis conducted in this study revealed that respiratory training enhanced hyoid bone movement but had no effect on swallowing quality of life. CONCLUSIONS: Respiratory training interventions may improve swallowing safety and efficiency in patients with dysphagia. However, the level of evidence is low, and there is a limited amount of research on the effectiveness and physiology of this intervention to improve swallowing function. In the future, there is a need to expand clinical studies, standardize measurement tools, and improve study protocols.
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Transtornos de Deglutição , Humanos , Transtornos de Deglutição/terapia , Deglutição , Qualidade de Vida , Resultado do TratamentoRESUMO
Esophagus cancer (EC) is a highly malignant and metastatic cancer. Poly(ADP-ribose) glycohydrolase (PARG), a DNA replication and repair regulator, inhibits cancer cell replication defects. This study aimed to explore the role of PARG in EC. The biological behaviors were analyzed using MTT assay, Transwell assay, scratch test, cell adhesion assay, and western blot. PARG expression was detected using quantitative PCR and immunohistochemical assay. The regulation of the Wnt/ß-catenin pathway was assessed using western blot. The results showed that PARG was highly expressed in EC tissues and cells. Knockdown of PARG suppressed cell viability, invasion, migration, adhesion, and epithelial-mesenchymal transition. Conversely, overexpression of PARG promoted the biological behaviors mentioned above. Moreover, overexpression of PARG promoted the activation of the Wnt/ß-catenin pathway rather than the STAT and Notch pathways. XAV939, the Wnt/ß-catenin pathway inhibitor, partly abolished the biological behaviors mediated by PARG overexpression. In conclusion, PARG promoted the malignant advancement of EC via activating the Wnt/ß-catenin pathway. These findings suggested that PARG might be a new therapeutic target for EC.
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Timely identification and discontinuation of culprit-drug is the cornerstone of clinical management of drug-induced acute pancreatitis (AP), but the comprehensive landscape of AP culprit-drugs is still lacking. To provide the current overview of AP culprit-drugs to guide clinical practice, we reviewed the adverse event (AE) reports associated with AP in the US Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) database from 2004 to 2022, and summarized a potential AP culprit-drug list and its corresponding AE report quantity proportion. The disproportionality analysis was used to detect adverse drug reaction (ADR) signals for each drug in the drug list, and the ADR signal distribution was integrated to show the risk characteristic of drugs according to the ADR signal detection results. In the FAERS database, a total of 62,206 AE reports were AP-related, in which 1,175 drugs were reported as culprit-drug. On the whole, metformin was the drug with the greatest number of AE reports, followed by quetiapine, liraglutide, exenatide, and sitagliptin. Drugs used in diabetes was the drug class with the greatest number of AE reports, followed by immunosuppressants, psycholeptics, drugs for acid-related disorders, and analgesics. In disproportionality analysis, 595 drugs showed potential AP risk, whereas 580 drugs did not show any positive ADR signal. According to the positive-negative distribution of the ADR signal for drug classes, the drug class with the greatest number of positive drugs was antineoplastic agents. In this study, we provided the current comprehensive landscape of AP culprit-drugs from the pharmacovigilance perspective, which can provide reference information for clinical practice.
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Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Pancreatite , Estados Unidos/epidemiologia , Humanos , Farmacovigilância , Sistemas de Notificação de Reações Adversas a Medicamentos , United States Food and Drug Administration , Doença Aguda , Pancreatite/induzido quimicamente , Pancreatite/epidemiologia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/diagnóstico , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologiaRESUMO
PURPOSE: To compare the effect of capsular bend on the rotational stability between 2 toric intraocular lenses (IOLs). SETTING: Eye Hospital of Wenzhou Medical University, Hangzhou, Zhejiang Province, China. DESIGN: Prospective study. METHODS: Patients with preexisting astigmatism received AcrySof IQ (SN6AT) or TECNIS (ZCT/ZMT) toric IOL during cataract surgery. CASIA2 was used to record the toric IOL axial orientation and capsular bend index (CBI) at the 1-day, 1-week, 1-month, and 3-month interval postoperatively. The postoperative rotational stability and CBI of both models were compared. RESULTS: A total of 58 eyes from 58 patients were enrolled in this study. The total misalignment of the TECNIS (ZCT/ZMT) group (6.96 ± 5.10 degrees, 7.41 ± 5.19 degrees, 6.93 ± 5.29 degrees, and 6.86 ± 5. 27 degrees) was significantly higher than that of the AcrySof IQ (SN6AT) group (3.55 ± 2.21 degrees, 4.00 ± 2.74 degrees, 3.72 ± 2.72 degrees, and 3.52 ± 2.50 degrees) at all follow-up intervals ( P < .05). The mean rotation of the TECNIS (ZCT/ZMT) group (2.66 ± 2.18 degrees) was significantly greater than that of the AcrySof IQ (SN6AT) group (1.65 ± 1.47 degrees) from 1 day to 1 week postoperatively ( P < .05). The capsular bend formation in the TECNIS (ZCT/ZMT) group was delayed compared with the AcrySof IQ (SN6AT) group ( P < .05, at the 1-week, 1-month, and 3-month interval). The TECNIS (ZCT/ZMT) group showed fibrosis in the peripheral anterior capsule, leading to its stretching away from the IOL surface, while the AcrySof IQ (SN6AT) group exhibited gentle adherence of the anterior capsule to the IOL surface. CONCLUSIONS: The AcrySof IQ toric IOL (SN6AT) exhibited greater rotational stability than the TECNIS toric IOL (ZCT/ZMT), which may partially result from the delay in capsular bend formation of TECNIS at the 1-day to 1-week follow-up postoperatively.
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Astigmatismo , Lentes Intraoculares , Facoemulsificação , Humanos , Refração Ocular , Implante de Lente Intraocular , Acuidade Visual , Estudos Prospectivos , Desenho de Prótese , Astigmatismo/cirurgiaRESUMO
Investigating immune memory to vaccinia virus and pre-existing immunity to mpox virus (MPXV) among the population is crucial for the global response to this ongoing mpox epidemic. Blood was sampled from vaccinees inoculated with vaccinia virus Tiantan (VTT) strain born before 1981 and unvaccinated control subjects born since 1982. After at least 40 years of the inoculation, 60% or 5% VTT vaccinees possess neutralizing antibodies (NAbs) to VTT or MPXV, with at least 50% having T cell memory to VTT protein antigens. Notably, 46.7% vaccinees show pre-existing T cell responses to MPXV. Broad pre-existing CD8+ T cell reactivities to MPXV are detected not only against conserved epitopes but also against variant epitopes between VTT and MPXV. Persistent NAbs and T cell memory to VTT among vaccinees, along with pre-existing T cells to MPXV among both vaccinees and the unvaccinated population, indicate a particular immune barrier to mpox.