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Exploring the complexity of the epithelial-to-mesenchymal transition (EMT) unveils a diversity of potential cell fates; however, the exact timing and mechanisms by which early cell states diverge into distinct EMT trajectories remain unclear. Studying these EMT trajectories through single-cell RNA sequencing is challenging due to the necessity of sacrificing cells for each measurement. In this study, we employed optimal-transport analysis to reconstruct the past trajectories of different cell fates during TGF-beta-induced EMT in the MCF10A cell line. Our analysis revealed three distinct trajectories leading to low EMT, partial EMT, and high EMT states. Cells along the partial EMT trajectory showed substantial variations in the EMT signature and exhibited pronounced stemness. Throughout this EMT trajectory, we observed a consistent downregulation of the EED and EZH2 genes. This finding was validated by recent inhibitor screens of EMT regulators and CRISPR screen studies. Moreover, we applied our analysis of early-phase differential gene expression to gene sets associated with stemness and proliferation, pinpointing ITGB4, LAMA3, and LAMB3 as genes differentially expressed in the initial stages of the partial versus high EMT trajectories. We also found that CENPF, CKS1B, and MKI67 showed significant upregulation in the high EMT trajectory. While the first group of genes aligns with findings from previous studies, our work uniquely pinpoints the precise timing of these upregulations. Finally, the identification of the latter group of genes sheds light on potential cell cycle targets for modulating EMT trajectories.
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Transición Epitelial-Mesenquimal , Análisis de la Célula Individual , Transición Epitelial-Mesenquimal/genética , Humanos , Análisis de la Célula Individual/métodos , Linaje de la Célula/genética , Factor de Crecimiento Transformador beta/metabolismo , Proteína Potenciadora del Homólogo Zeste 2/metabolismo , Proteína Potenciadora del Homólogo Zeste 2/genéticaRESUMEN
Determining gene regulatory network (GRN) structure is a central problem in biology, with a variety of inference methods available for different types of data. For a widely prevalent and challenging use case, namely single-cell gene expression data measured after intervention at multiple time points with unknown joint distributions, there is only one known specifically developed method, which does not fully utilize the rich information contained in this data type. We develop an inference method for the GRN in this case, netWork infErence by covariaNce DYnamics, dubbed WENDY. The core idea of WENDY is to model the dynamics of the covariance matrix, and solve this dynamics as an optimization problem to determine the regulatory relationships. To evaluate its effectiveness, we compare WENDY with other inference methods using synthetic data and experimental data. Our results demonstrate that WENDY performs well across different data sets.
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A cross-sectional study was conducted on the 12th month of using the voice nursing and health education system. Work sampling method was used to observe for 120 hours, and 39 satisfaction questionnaires were collected. The results showed that the usage rate of voice health education system accounted for 14.3% of nursing guidance tools. Pearson analysis showed that user satisfaction and usage efficiency had the greatest impact (p < .001). When the system's ease of operation and stability meet expectations, the care guidance process can be improved.
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Educación en Salud , Estudios Transversales , Humanos , Encuestas y CuestionariosRESUMEN
Background and Aims: Besides hospital size, clinical diagnosis and severity of patient cases determine the total platelet usage. Therefore, the appropriateness of platelet usage could not be compared simply with the total units of platelet usage in each hospital. This study aimed to objectively monitor and analyze platelet usage after implementing a single-unit issuing policy for each platelet transfusion in our hospital in October 2020. Materials and Methods: We used three objective indices, X, Y, and Z, to monitor platelet usage and compared it with other hospitals. Three indices were generated by dividing the annual total units of platelet usage by the total annual reimbursement, total number of admissions, and average total reimbursement per admission for each hospital. Results: The new indices X and Y alleviated hospital size-dependent differences. Index Y was preferred over X because its value fluctuated less during the COVID-19 pandemic. The Z index was adjusted for the average total reimbursement per admission, and the results showed that more patients with higher disease complexity did not have increased platelet usage during the COVID-19 pandemic. In our hospital (H1), index Z decreased from 2019 to 2021 due to a policy of issuing a single unit for each platelet transfusion. Conclusion: These three objective indices are suitable for peer comparison and monitoring platelet usage in hospitals, irrespective of their size. They could be applied to promote patient blood management and provide an early response to the gradual shortage of blood resources owing to the aging population and declining birth rate in Taiwan.
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BACKGROUND: Real-world vaccine effectiveness following the third dose of vaccination against SARS-CoV-2 remains less investigated among people with HIV (PWH). METHODS: PWH receiving the third dose of BNT162b2 and mRNA-1273 (either 50- or 100-µg) were enrolled. Participants were followed for 180 days until the fourth dose of COVID-19 vaccination, SARS-CoV-2 infection, seroconversion of anti-nucleocapsid IgG, death, or loss to follow-up. Anti-spike IgG was determined every 1-3 months. RESULTS: Of 1427 participants undergoing the third-dose COVID-19 vaccination, 632 (44.3%) received 100-µg mRNA-1273, 467 (32.8%) 50-µg mRNA-1273, and 328 (23.0%) BNT162b2 vaccine and the respective rate of SARS-CoV-2 infection or seroconversion of anti-nucleocapsid IgG was 246.1, 280.8 and 245.2 per 1000 person-months of follow-up (log-rank test, p = 0.28). Factors associated with achieving anti-S IgG titers >1047 BAU/mL included CD4 count <200 cells/mm3 (adjusted odds ratio [aOR], 0.11; 95% CI, 0.04-0.31), plasma HIV RNA >200 copies/mL (aOR, 0.27; 95% CI, 0.09-0.80), having achieved anti-spike IgG >141 BAU/mL within 3 months after primary vaccination (aOR, 3.69; 95% CI, 2.68-5.07), receiving BNT162b2 vaccine as the third dose (aOR, 0.20; 95% CI, 0.10-0.41; reference, 100-µg mRNA-1273), and having previously received two doses of mRNA vaccine in primary vaccination (aOR, 2.46; 95% CI, 1,75-3.45; reference, no exposure to mRNA vaccine). CONCLUSIONS: PWH receiving different types of the third dose of COVID-19 vaccine showed similar vaccine effectiveness against SARS-CoV-2 infection. An additional dose with 100-µg mRNA-1273 could generate a higher antibody response than with 50-µg mRNA-1273 and BNT162b2 vaccine.
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Vacuna nCoV-2019 mRNA-1273 , Anticuerpos Antivirales , Vacuna BNT162 , Vacunas contra la COVID-19 , COVID-19 , Infecciones por VIH , Inmunoglobulina G , SARS-CoV-2 , Glicoproteína de la Espiga del Coronavirus , Humanos , Masculino , Femenino , COVID-19/prevención & control , COVID-19/inmunología , Anticuerpos Antivirales/sangre , Persona de Mediana Edad , Infecciones por VIH/inmunología , Glicoproteína de la Espiga del Coronavirus/inmunología , Vacuna BNT162/administración & dosificación , Vacuna BNT162/inmunología , SARS-CoV-2/inmunología , Inmunoglobulina G/sangre , Adulto , Vacuna nCoV-2019 mRNA-1273/inmunología , Vacuna nCoV-2019 mRNA-1273/administración & dosificación , Vacunas contra la COVID-19/inmunología , Vacunas contra la COVID-19/administración & dosificación , Vacunación/métodos , Eficacia de las Vacunas , SeroconversiónRESUMEN
BACKGROUND: Information on the protein-based severe acute respiratory syndrome (SARS-CoV-2) vaccine-NVX-CoV2373 (Novavax), as a heterologous booster remains limited. We investigated the immunogenicity and adverse events of NVX-CoV2373 as a second booster and compared them with those of mRNA vaccines in healthy adults. METHODS: Healthcare workers who had received an mRNA vaccine (mRNA-1273 or BNT-162b2) as the first booster (third dose) 12 weeks prior were recruited. Participants voluntarily received either NVX-CoV2373 or an mRNA vaccine as a second booster. Participants with a history of SARS-CoV-2 infection were excluded. The primary outcomes included serum anti-SARS-CoV-2 spike protein (SP) and neutralizing antibody titers against B.1.1.7 (Alpha), B.1.1.529 (Omicron) BA2, and BA5 variants on the 28th day after the boost. Secondary outcomes included new SARS-CoV-2 infections and adverse events reported during the study period. RESULTS: A total of 160 participants were enrolled in this study. Compared with the mRNA vaccination group (n = 59), the NVX-CoV2373 vaccination group (n = 101) had significantly lower anti-SARS-CoV-2 SP antibody titers and neutralizing antibody titers against all variants tested after the boost. During the study period, higher rates of new SARS-CoV-2 infections and a lower incidence of adverse events were observed in the NVX-CoV2373 vaccination group. No significant differences in cellular immune responses were observed between the two groups. CONCLUSION: Compared to a homologous mRNA booster vaccination, heterologous boosters with NVX-CoV2373 showed lower antibody responses, a higher incidence of new SARS-CoV-2 infections, and fewer adverse events.
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Vacunas contra la COVID-19 , COVID-19 , Adulto , Humanos , Vacunas contra la COVID-19/efectos adversos , Vacunas de ARNm , SARS-CoV-2 , COVID-19/prevención & control , ARN Mensajero , Anticuerpos Neutralizantes , Anticuerpos AntiviralesRESUMEN
BACKGROUND: Real-time surveillance of COVID-19 in large-scale community outbreaks presents challenges. Simple counts of the daily confirmed cases can be misleading due to constraints from bottlenecks in access to care or laboratory testing. This study aimed to investigate the role of the SARS-CoV-2 antigen rapid diagnostic test (Ag-RDT) in addressing these challenges for real-time COVID-19 surveillance. METHODS: This study included the results of 86,994 SARS-CoV-2 Ag-RDT and real-time reverse transcription polymerase chain reaction (RT-PCR) tests. These were conducted at four community testing stations within the Taipei metropolitan area during a community COVID-19 outbreak spanning from May 17, 2021, to August 9, 2021. We examined the correlation between the positive rates of Ag-RDT tests and the epidemic curve of laboratory-confirmed COVID-19 cases by onset date to examine its role in real-time surveillance. RESULTS: During the 85-day study period, the trend of Ag-RDT test positive rates paralleled that of the epidemic curve. The correlation between the Ag-RDT positive rate and the number of cases (Pearson correlation coefficient: 0.968) is comparable to that of the RT-PCR positive rate (Pearson correlation coefficient: 0.964). The Ag-RDT positive rate exhibited a more advanced leading trend, with Ag-RDT leading by 3 days in comparison to the 2-day lead for RT-PCR. CONCLUSION: The positive rate of SARS-CoV-2 Ag-RDT tests at community testing stations serves as a good surrogate for assessing virus activity within the community and a useful tool for real-time COVID-19 surveillance. It is a robust indicator of the outbreak trend and near-term numbers of cases. This finding may facilitate the management of subsequent outbreaks of emerging infectious diseases.
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Cyclin-dependent kinases 4/6 (CDK4/6) inhibitors such as palbociclib are approved for the treatment of metastatic estrogen receptor-positive (ER+) breast cancer in combination with endocrine therapies and significantly improve outcomes in patients with this disease. However, given the large number of possible pairwise drug combinations and administration schedules, it remains unclear which clinical strategy would lead to best survival. Here, we developed a computational, cell cycle-explicit model to characterize the pharmacodynamic response to palbociclib-fulvestrant combination therapy. This pharmacodynamic model was parameterized, in a Bayesian statistical inference approach, using in vitro data from cells with wild-type estrogen receptor (WT-ER) and cells expressing the activating missense ER mutation, Y537S, which confers resistance to fulvestrant. We then incorporated pharmacokinetic models derived from clinical data into our computational modeling platform. To systematically compare dose administration schedules, we performed in silico clinical trials based on integrating our pharmacodynamic and pharmacokinetic models as well as considering clinical toxicity constraints. We found that continuous dosing of palbociclib is more effective for lowering overall tumor burden than the standard, pulsed-dose palbociclib treatment. Importantly, our mathematical modeling and statistical analysis platform provides a rational method for comparing treatment strategies in search of optimal combination dosing strategies of other cell-cycle inhibitors in ER+ breast cancer. SIGNIFICANCE: We created a computational modeling platform to predict the effects of fulvestrant/palbocilib treatment on WT-ER and Y537S-mutant breast cancer cells, and found that continuous treatment schedules are more effective than the standard, pulsed-dose palbociclib treatment schedule.
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Neoplasias de la Mama , Humanos , Femenino , Neoplasias de la Mama/tratamiento farmacológico , Fulvestrant , Receptores de Estrógenos/análisis , Teorema de BayesRESUMEN
We report the mixotrophic growth of Escherichia coli based on recombinant 2-oxoglutarate:ferredoxin oxidoreductase (OGOR) to assimilate CO2 using malate as an auxiliary carbon source and hydrogen as an energy source. We employ a long-term (~184 days) two-stage adaptive evolution to convert heterotrophic E. coli into mixotrophic E. coli. In the first stage of evolution with serine, diauxic growth emerges as a prominent feature. At the end of the second stage of evolution with malate, the strain exhibits mixotrophy with CO2 as an essential substrate for growth. We expect this work will open new possibilities in the utilization of OGOR for microbial CO2 assimilation and future hydrogen-based electro-microbial conversion.
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The new generation of nonvitamin K antagonists are broadly applied for stroke prevention due to their notable efficacy and safety. Our study aimed to develop a suggestive utilization of dabigatran through an integrated machine learning (ML) decision-tree model. Participants taking different doses of dabigatran in the Randomized Evaluation of Long-Term Anticoagulant Therapy trial were included in our analysis and defined as the 110 mg and 150 mg groups. The proposed scheme integrated ML methods, namely naive Bayes, random forest (RF), classification and regression tree (CART), and extreme gradient boosting (XGBoost), which were used to identify the essential variables for predicting vascular events in the 110 mg group and bleeding in the 150 mg group. RF (0.764 for 110 mg; 0.747 for 150 mg) and XGBoost (0.708 for 110 mg; 0.761 for 150 mg) had better area under the receiver operating characteristic curve (AUC) values than logistic regression (benchmark model; 0.683 for 110 mg; 0.739 for 150 mg). We then selected the top ten important variables as internal nodes of the CART decision tree. The two best CART models with ten important variables output tree-shaped rules for predicting vascular events in the 110 mg group and bleeding in the 150 mg group. Our model can be used to provide more visualized and interpretable suggestive rules to clinicians managing NVAF patients who are taking dabigatran.
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Fibrilación Atrial , Dabigatrán , Humanos , Dabigatrán/uso terapéutico , Dabigatrán/efectos adversos , Fibrilación Atrial/tratamiento farmacológico , Teorema de Bayes , Hemorragia/inducido químicamente , Hemorragia/epidemiología , Aprendizaje Automático , Árboles de DecisiónRESUMEN
Although real-time reverse transcriptase polymerase chain reaction (real-time RT-PCR) remains as a golden standard for detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, it can not be easily expanded to large-scaled screening during outbreaks, and the positive results do not necessarily correlate with infectious status of the identified subjects. In this study, the performance of Vstrip® RV2 COVID-19 Antigen Rapid Test (RAT) and its correlation with virus infectivity was examined by virus culture using 163 sequential respiratory specimens collected from 26 SARS-CoV-2 infected patients. When the presence of cytopathic effects (CPE) in cell culture was used as a reference method for virus infectivity, the sensitivity, specificity and accuracy of Vstrip® RV2 COVID-19 Antigen Rapid Test was 96.43%, 89.63%, and 90.8%, respectively. The highest Ct value was 27.7 for RdRp gene and 25.79 for E gene within CPE-positive samples, and the highest Ct value was 31.9 for RdRp gene and 29.1 for E gene within RAT positive samples. When the Ct values of specimens were below 25, the CPE and RAT results had high degree of consistency. We concluded that the RAT could be a great alternative method for determining the infectious potential of individuals with high viral load.
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Background: A community COVID-19 outbreak caused by the B.1.1.7 SARS-CoV-2 variant occurred in Taiwan in May 2021. High-risk populations such as people living with HIV (PLWH) were recommended to receive two doses of COVID-19 vaccines. While SARS-CoV-2 vaccines have demonstrated promising results in general population, real-world information on the serological responses remains limited among PLWH. Methods: PLWH receiving the first dose of SARS-CoV-2 vaccine from 2020 to 2021 were enrolled. Determinations of anti-SARS-CoV-2 spike IgG titers were performed every one to three months, the third dose of the SARS-CoV-2 vaccine or confirmed SARS-CoV-2 infection. All serum samples were tested for anti-nucleocapsid antibody and those tested positive were excluded from analysis. Results: A total of 1189 PLWH were enrolled: 829 (69.7%) receiving two doses of the AZD1222 vaccine, 232 (19.5%) of the mRNA-1273 vaccine, and 128 (10.8%) of the BNT162b2 vaccine. At all time-points, PLWH receiving two doses of mRNA vaccines had consistently higher antibody levels than those receiving the AZD1222 vaccine (p <0.001 for all time-point comparisons). Factors associated with failure to achieve an anti-spike IgG titer >141 BAU/mL within 12 weeks, included type 2 diabetes mellitus (DM) (adjusted odds ratio [aOR], 2.24; 95% CI, 1.25-4), a CD4 T cell count <200 cells/mm3 upon receipt of the first dose of vaccination (aOR, 3.43; 95% CI, 1.31-9) and two homologous AZD1222 vaccinations (aOR, 16.85; 95%CI, 10.13-28). For those receiving two doses of mRNA vaccines, factors associated with failure to achieve an anti-spike IgG titer >899 BAU/mL within 12 weeks were a CD4 T cell count <200 cells/mm3 on first-dose vaccination (aOR, 3.95; 95% CI, 1.08-14.42) and dual BNT162b2 vaccination (aOR, 4.21; 95% CI, 2.57-6.89). Conclusions: Two doses of homologous mRNA vaccination achieved significantly higher serological responses than vaccination with AZD1222 among PLWH. Those with CD4 T cell counts <200 cells/mm3 and DM had consistently lower serological responses.
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Glioblastoma is believed to be one of the most aggressive brain tumors in the world. ONX-0914 (PR957) is a selective inhibitor of proteasome subunit beta type-8 (PSMB8). Previous studies have shown that inhibiting PSMB8 expression in glioblastoma reduces tumor progression. Therefore, this study aimed to determine whether ONX-0914 has antitumor effects on human glioblastoma. The results indicated that ONX-0914 treatment inhibited survival in LN229, GBM8401, and U87MG glioblastoma cells. Cell cycle analysis showed that ONX-0914 treatment caused cell cycle arrest at the G1 phase and apoptosis in glioblastoma cells. The protein expression of BCL-2 was reduced and PARP was cleaved after ONX-0914 treatment. Furthermore, the levels of p53 and phosphorylated p53 were increased by ONX-0914 treatment in glioblastoma cells. ONX-0914 also induced autophagy in glioblastoma cells. Furthermore, the p53 inhibitor pifithrin attenuated apoptosis but enhanced autophagy caused by ONX-0914. In an orthotopic mouse model, TMZ plus ONX-0914 reduced tumor progression better than the control or TMZ alone. These data suggest that ONX-0914 is a novel therapeutic drug for glioblastoma.
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We describe a numerical algorithm for approximating the equilibrium-reduced density matrix and the effective (mean force) Hamiltonian for a set of system spins coupled strongly to a set of bath spins when the total system (system + bath) is held in canonical thermal equilibrium by weak coupling with a "super-bath". Our approach is a generalization of now standard typicality algorithms for computing the quantum expectation value of observables of bare quantum systems via trace estimators and Krylov subspace methods. In particular, our algorithm makes use of the fact that the reduced system density, when the bath is measured in a given random state, tends to concentrate about the corresponding thermodynamic averaged reduced system density. Theoretical error analysis and numerical experiments are given to validate the accuracy of our algorithm. Further numerical experiments demonstrate the potential of our approach for applications including the study of quantum phase transitions and entanglement entropy for long range interaction systems.
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In prosthodontics, the ability of glass-ceramics to express the optical properties of natural teeth is an important goal of esthetic restorations. Dental restorations do not merely need to be similar in color to natural teeth; proper optical properties, such as opalescence, transparency, etc., must be combined in order to achieve excellent esthetic effects. The optical properties of ceramic materials are mainly distinguished by different hues (e.g., A, B, C, and D) combined with translucency (e.g., high translucency (HT), medium translucency (MT), low translucency (LT), and medium opacity (MO)). However, there are many varieties of tooth color. Therefore, it is expected that glass-ceramics can change their nanocrystal size and porosity through different heat-treatment temperatures and times and, thereby, present different transparency effects. This study mainly analyzed the influence of changes in sintering temperature on the optical properties of glass-ceramics. The optical properties of glass-ceramics in the oral cavity were evaluated with human trials. We hypothesized that (1) the transparency of glass-ceramics can be changed by controlling the sintering temperature and (2) glass-ceramics modified by the sintering temperature can be suitable for clinical applications. Results showed that the transparency decreased, the nanoparticle size increased, the crystallinity increased, and the surface hardness decreased as the sintering temperature increased. High-brightness glass-ceramics have more-sensitive optical properties. Results of clinical trials showed that glass-ceramics whose transparency was changed by controlling the sintering temperature can be candidates for clinical applications. Based on the above results, the hypotheses of this study were supported. In the future, we will continue to explore the esthetic field of dental restorations.
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Hypertension and pain are both prevalent conditions in the older adult population. We aimed to report the prevalence of pain discomforts and investigated the association between hypertension and pain discomforts among older adults in the United States. Data from the 2011 National Health and Aging Trends Study were analyzed. In-person interviews were conducted in 7601 adults ages ≥ 65 years. Prevalence of bothersome pain, activity-limiting pain, locations of pain and usage of pain medicine were evaluated. Demographics, comorbidities, and other covariates were compared between older adults with hypertension and those without. Multivariate regression was further performed to yield adjusted odd ratios. Among 6825 older adults, 4533 of them had a history of hypertension while 2272 of them had not. Prevalence of bothersome pain (57.12% versus 44.81%, p < 0.001) and activity-limiting pain (56.21% versus 46.12%, p < 0.001) were significantly higher in the hypertension group. After adjusting for all covariates, hypertension demonstrated a significant association with activity-limiting pain (OR 1.63, 95% CI 1.06 to 2.52, p = 0.02). In conclusion, pain was more prevalent in older Americans with hypertension. The positive association between hypertension and pain suggested that routine pain assessment and proper treatment would be required to improve the function and quality of life among older adults especially with hypertension.
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Hipertensión , Vida Independiente , Anciano , Humanos , Hipertensión/complicaciones , Hipertensión/epidemiología , Dolor/epidemiología , Prevalencia , Calidad de Vida , Estados Unidos/epidemiologíaRESUMEN
Our study aims to develop an effective integrated machine learning (ML) scheme to predict vascular events and bleeding in patients with nonvalvular atrial fibrillation taking dabigatran and identify important risk factors. This study is a post-hoc analysis from the Randomized Evaluation of Long-Term Anticoagulant Therapy trial database. One traditional prediction method, logistic regression (LGR), and four ML techniques-naive Bayes, random forest (RF), classification and regression tree, and extreme gradient boosting (XGBoost)-were combined to construct our scheme. Area under the receiver operating characteristic curve (AUC) of RF (0.780) and XGBoost (0.717) was higher than that of LGR (0.674) in predicting vascular events. In predicting bleeding, AUC of RF (0.684) and XGBoost (0.618) showed higher values than those generated by LGR (0.605). Our integrated ML feature selection scheme based on the two convincing prediction techniques identified age, history of congestive heart failure and myocardial infarction, smoking, kidney function, and body mass index as major variables of vascular events; age, kidney function, smoking, bleeding history, concomitant use of specific drugs, and dabigatran dosage as major variables of bleeding. ML is an effective data analysis algorithm for solving complex medical data. Our results may provide preliminary direction for precision medicine.
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(1) Background: Bladder cancer is a malignant tumor mainly caused by exposure to environmental chemicals, with a high recurrence rate. NR1H4, also known as Farnesoid X Receptor (FXR), acts as a nuclear receptor that can be activated by binding with bile acids, and FXR is highly correlated with the progression of cancers. The aim of this study was to verify the role of FXR in bladder cancer cells. (2) Methods: A FXR overexpressed system was established to investigate the effect of cell viability, migration, adhesion, and angiogenesis in low-grade TSGH8301 and high-grade T24 cells. (3) Results: After FXR overexpression, the ability of migration, adhesion, invasion and angiogenesis of bladder cancer cells declined significantly. Focal adhesive complex, MMP2, MMP9, and angiogenic-related proteins were decreased, while FXR was overexpressed in bladder cancer cells. Moreover, FXR overexpression reduced vascular endothelial growth factor mRNA and protein expression and secretion in bladder cancer cells. After treatment with the proteosome inhibitor MG132, the migration, adhesion and angiogenesis caused by FXR overexpression were all reversed in bladder cancer cells. (4) Conclusions: These results may provide evidence on the role of FXR in bladder cancer, and thus may improve the therapeutic efficacy of urothelial carcinoma in the future.
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Carcinoma de Células Transicionales , Receptores Citoplasmáticos y Nucleares/metabolismo , Neoplasias de la Vejiga Urinaria , Línea Celular Tumoral , Femenino , Humanos , Masculino , Neovascularización Patológica/genética , Complejo de la Endopetidasa Proteasomal , Neoplasias de la Vejiga Urinaria/genética , Neoplasias de la Vejiga Urinaria/patología , Factor A de Crecimiento Endotelial Vascular/genética , Factores de Crecimiento Endotelial VascularRESUMEN
Background: Oral mucositis (OM) is a common side effect of radiotherapy (RT) that can have severe implications in patients with head and neck cancer (HNC). Traditional Chinese medicine (TCM) formula is widely applied in treating OM, but little substantial evidence exists to clarify it effects. The study intends to determine whether the TCM-based prescription in treating HNC with RT can improve the OM when compared with RT alone. Methods: A single-center, randomized, two-arm parallel-group, open-label controlled clinical trial will be conducted to determine whether the Zi-Yin-Liang-Ge-San (ZYLGS), which contains Rx. Scutellariae, Rx. Glycyrrhizae, Hb. Dendrobii, Rx. Ophiopogonis, and Hb. Menthae Haplocalycis, combined with RT can improve the incidence and severity of OM. Two hundred participants will randomly 1:1 to receive at least 6 weeks of RT plus ZYLGS powder or control. The primary outcome measures are onset, gradation of OM (Common Terminology Criteria for Adverse Events v5.0), and oral pain (visual analogue scale). The secondary outcome measures include nutritional status, the EORTC Quality of Life Core Questionnaire and head and neck module. The Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events, serious adverse events, and blood and biochemical analysis will be recorded to evaluate the safety. Visits will be performed for each week during the RT treatment period and then 2 weeks in the follow-up period. Discussion: The study's result will provide a high-level evidence for TCM-based formulation for HNC patients with RT on the effect of OM prevention and management.