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Colorectal cancer (CRC) remains a highly prevalent gastrointestinal neoplasm, presenting significant prevalence and lethality rate. DEAD/H box RNA helicase 10 (DDX10) has been proposed as a potential oncogene in CRC, the specific action mechanism by which DDX10 modulates the aggressive biological cellular events in CRC remains implicitly elucidated, however. During this study, DDX10 expression was detected via RT-qPCR and Western blotting. Cell proliferation was estimated via EDU staining. TUNEL staining and Western blotting appraised cell apoptosis. Cell stemness was evaluated by sphere formation assay, RT-qPCR, Western blotting as well as immunofluorescence staining. Relevant assay kit examined aldehyde dehydrogenase (ALDH) activity. Western blotting and immunofluorescence staining also detected autophagy. DDX10 was hyper-expressed in CRC cells. Down-regulation of DDX10 hampered cell proliferation, aggravated the apoptosis while eliminated the ability to form spheroid cells in CRC. In addition, DDX10 deletion improved ATG10 expression and therefore activated autophagy in CRC cells. Consequently, ATG10 depletion or treatment with autophagy inhibitor 3-Methyladenine (3-MA) partially compensated the influences of DDX10 silencing on the proliferation, apoptosis and stemness of CRC cells. Accordingly, DDX10 deficiency may aggravate autophagy mediated by ATG10 to impede cell proliferation, stemness and facilitate cell apoptosis, hence blocking the progression of CRC.
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Apoptosis , Proteínas Relacionadas con la Autofagia , Autofagia , Proliferación Celular , Neoplasias Colorrectales , ARN Helicasas DEAD-box , Células Madre Neoplásicas , Humanos , Neoplasias Colorrectales/patología , Neoplasias Colorrectales/metabolismo , Neoplasias Colorrectales/genética , Autofagia/fisiología , ARN Helicasas DEAD-box/genética , ARN Helicasas DEAD-box/metabolismo , Proteínas Relacionadas con la Autofagia/metabolismo , Proteínas Relacionadas con la Autofagia/genética , Células Madre Neoplásicas/patología , Células Madre Neoplásicas/metabolismo , Línea Celular Tumoral , Enzimas Ubiquitina-Conjugadoras/metabolismo , Enzimas Ubiquitina-Conjugadoras/genética , Ratones , Animales , Proteínas de Transporte VesicularRESUMEN
Glioblastoma (GBM), as the most common primary brain tumor, usually results in an extremely poor prognosis, in which glioma stem cells (GSCs) and their immunosuppressive microenvironment prominently intervene in the resistance to radiotherapy and chemotherapy that directly leads to tumor recurrence and shortened survival time. The specific mechanism through which exosomes generated from GSCs support the creation of an immunosuppressive microenvironment remains unknown, while it is acknowledged to be engaged in intercellular communication and the regulation of the glioma immunosuppressive microenvironment. The elevated expression of LncRNA-NEAT1 was found in glioma cells after radiotherapy, chemotherapy, and DNA damage stimulation, and NEAT1 could promote the malignant biological activities of GSCs. Emerging evidence suggests that lncRNAs may reply to external stimuli or DNA damage by playing a role in modulating different aspects of tumor biology. Our study demonstrated a promotive role of the carried NEAT1 by GSC-derived exosomes in the polarization of M2-like macrophages. Further experiments demonstrated the mediative role of miR-125a and its target gene STAT3 in NEAT1-induced polarization of M2-like macrophages that promote glioma progression. Our findings elucidate the mechanism by which GSCs influence the polarization of M2-like macrophages through exosomes, which may contribute to the formation of immunosuppressive microenvironments. Taken together, our study reveals the miR-125a-STAT3 pathway through which exosomal NEAT1 from treatment-resistant GSCs contributes to M2-like macrophage polarization, indicating the potential of exosomal NEAT1 for treating glioma.
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OBJECTIVE: Given the high prevalence of hypertension among Chinese adults, this population is at a significantly increased risk of severe COVID-19 complications. The purpose of this study is to assess the willingness of Chinese hypertensive adults to receive the COVID-19 vaccine and to identify the diverse factors that shape their vaccination decisions. METHODS: Sampling was conducted utilizing multistage stratified random sampling, and ultimately, a total of 886 adult hypertensive patients from Luzhou City in Southwest China were included in this study. The questionnaire design was based on the Theory of Planned Behaviour and was used to investigate their willingness to be vaccinated with COVID-19. Structural equation modeling was employed for data analysis. RESULTS: The results showed that 75.6% of hypertensive individuals were willing to receive COVID-19 vaccination. The structural equation modeling revealed that Subjective Norms (path coefficient = 0.361, CR = 8.049, P < 0.001) and Attitudes (path coefficient = 0.253, CR = 4.447, P < 0.001) had positive effects on vaccination willingness, while Perceived Behavioral Control (path coefficient=-0.004, CR=-0.127, P = 0.899) had no significant impact on Behavioral Attitudes. Mediation analysis indicated that Knowledge (indirect path coefficient = 0.032, LLCI = 0.014, ULCI = 0.058), Risk Perception (indirect path coefficient = 0.077, LLCI = 0.038, ULCI = 0.124), and Subjective Norms (indirect path coefficient = 0.044, LLCI = 0.019, ULCI = 0.087) significantly influenced vaccination willingness through Attitudes as a mediating factor. CONCLUSION: The willingness of hypertensive individuals to receive the COVID-19 vaccination is not satisfactory. The Theory of Planned Behavior provides valuable insights into understanding their vaccination intentions. Efforts should be concentrated on enhancing the subjective norms, attitudes, and knowledge about vaccination of hypertensive patients.
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Vacunas contra la COVID-19 , COVID-19 , Hipertensión , Intención , SARS-CoV-2 , Vacunación , Humanos , Hipertensión/epidemiología , Hipertensión/psicología , COVID-19/prevención & control , COVID-19/epidemiología , COVID-19/psicología , Masculino , Femenino , China/epidemiología , Persona de Mediana Edad , Vacunas contra la COVID-19/administración & dosificación , Vacunación/psicología , Vacunación/estadística & datos numéricos , Adulto , Encuestas y Cuestionarios , Análisis de Clases Latentes , Anciano , Conocimientos, Actitudes y Práctica en Salud , Aceptación de la Atención de Salud/psicología , Aceptación de la Atención de Salud/estadística & datos numéricos , Estudios Transversales , Pueblos del Este de AsiaRESUMEN
BACKGROUND: Surgery and postoperative adjuvant therapy is the standard treatment for locally advanced resectable oral squamous cell carcinoma (OSCC), while neoadjuvant chemoimmunotherapy (NACI) is believed to lead better outcomes. This study aims to investigate the effectiveness of NACI regimens in treating locally advanced resectable OSCC. MATERIALS AND METHODS: Patients diagnosed with locally advanced resectable OSCC who received NACI and non-NACI were reviewed between December 2020 and June 2022 in our single center. The pathologic response was evaluated to the efficacy of NACI treatment. Adverse events apparently related to NACI treatment were graded by Common Terminology Criteria for Adverse Events, version 5.0. Disease-free survival (DFS) and overall survival (OS) rate were assessed. RESULTS: Our analysis involved 104 patients who received NACI. Notably, the pathological complete response (PCR) rate was 47.1%, and the major pathological response (MPR) rate was 65.4%. The top three grade 1-2 treatment-related adverse events (TRAEs) were alopecia (104; 100%), anemia (81; 77.9%) and pruritus (62; 59.6%). Importantly, patients achieving MPR exhibited higher programmed cell death-ligand 1 (PD-L1) combined positive score (CPS). The diagnostic value of CPS as a biomarker for NACI efficacy was enhanced when combined total cholesterol level. The 3-year estimated DFS rates were 89.0% in the NACI cohort compared to 60.8% in the non-NACI cohort, while the 3-year estimated OS rates were 91.3% versus 64.0%, respectively. CONCLUSIONS: The NACI treatment showed safe and encouragingly efficacious for locally advanced resectable OSCC patients. The high response rates and favorable prognosis suggest this approach as a potential treatment option. Prospective randomized controlled trials are needed to further validate these findings.
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Clear cell renal cell carcinoma (ccRCC), the most common type of renal cell carcinoma (RCC), is not sensitive to traditional radiotherapy and chemotherapy. The polyphenolic compound Gallic acid (GA) can be naturally found in a variety of fruits, vegetables and plants. Autophagy, an intracellular catabolic process, regulates the lysosomal degradation of organelles and portions in cytoplasm. It was reported that autophagy and GA could affect the development of several cancers. Therefore, the aim of the present study was to evaluate the effects of GA on ccRCC development and clarify the role of autophagy in this process. In the present study, the effects of GA on the proliferation, migration and invasion of ccRCC cells were investigated in vitro by Cell Counting Kit8, colony formation, flow cytometry, wound healing and Transwell migration assays, respectively. Additionally, the effects of GA on ccRCC growth and metastasis were evaluated using hematoxylineosin and immunohistochemical staining in vivo. Moreover, it was sought to explore the underlying molecular mechanisms using transmission electron microscopy, western blotting and reverse transcriptionquantitative PCR analyses. In the present study, it was revealed that GA had a more potent viability inhibitory effect on ccRCC cells (786O and ACHN) than the effect on normal renal tubular epithelial cell (HK2), which demonstrated that GA selectively inhibits the viability of cancer cells. Furthermore, it was identified that GA dosedependently inhibited the proliferation, migration and invasion of ccRCC cells in vitro and in vivo. It was demonstrated that GA promoted the release of autophagy markers, which played a role in regulating the PI3K/Akt/Atg16L1 signaling pathway. All the aforementioned data provided evidence for the great potential of GA in the treatment of ccRCC.
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Autofagia , Carcinoma de Células Renales , Ácido Gálico , Neoplasias Renales , Transducción de Señal , Animales , Femenino , Humanos , Masculino , Ratones , Autofagia/efectos de los fármacos , Proteínas Relacionadas con la Autofagia/metabolismo , Proteínas Relacionadas con la Autofagia/genética , Carcinoma de Células Renales/tratamiento farmacológico , Carcinoma de Células Renales/patología , Proteínas Portadoras/metabolismo , Línea Celular Tumoral , Movimiento Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Progresión de la Enfermedad , Ácido Gálico/farmacología , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Neoplasias Renales/tratamiento farmacológico , Neoplasias Renales/patología , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Transducción de Señal/efectos de los fármacos , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
OBJECTIVE: Radial Forearm Free flap (RFFF) is widely used in head and neck reconstruction, yet its donor site defect remains a significant drawback. The Medial Sural Artery Perforator Free Flap (MSAPFF) is considered an alternative flap to RFFF. This study aims to comprehensively analyze their characteristics, outcomes, and their impact on patient quality of life. METHODS: All patients who underwent oral cavity reconstruction using RFFF and MSAPFF between February 2017 and April 2023 were included in this study. Flap characteristics, outcomes and post-operative complications were recorded and compared. Subjective donor site morbidity, aesthetic and functional results, and quality of life were also analyzed. RESULTS: The study included 76 patients: 37 underwent reconstruction with RFFF, and 39 with MSAPFF. There was no significance difference between the RFFF and MSAPFF regarding the success rate (97.2% vs 97.4%), flap size (4.8 × 8.8 cm2 vs 5 × 9.8 cm2), hospital of stay (15.5 days vs 13.5 days) and recipient site complications (P > 0.05). However, MSAPFF showed larger flap thickness (P = 0.001), smaller arterial caliber (P = 0.008), shorter pedicle length (P = 0.001), and longer harvesting time (P < 0.001). No significant difference was observed between the pre-and postoperative ranges of wrist and ankle movements or in recipient site complications. MSAPFF showed a significant difference in donor site morbidity (P < 0.05). CONCLUSION: The MSAPFF is an excellent alternative to the RFFF for repairing oral cavity defects, with additional advantage of a well-hidden scar on the posterior calf, a larger flap thickness, accepted pedicle length and arterial caliber. However, one should consider the harvesting time and surgical skills required in comparison to the RFFF. CLINICAL RELEVANCE: The study highlights the importance of the MSAPFF as an alternative option for RFFF with less donor site morbidity and high success rate in oral cavity reconstruction and improved patient Quality of life after ablative surgery.
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Antebrazo , Colgajos Tisulares Libres , Colgajo Perforante , Procedimientos de Cirugía Plástica , Complicaciones Posoperatorias , Calidad de Vida , Humanos , Femenino , Masculino , Persona de Mediana Edad , Procedimientos de Cirugía Plástica/métodos , Colgajo Perforante/irrigación sanguínea , Antebrazo/cirugía , Sitio Donante de Trasplante/cirugía , Adulto , Anciano , Estudios Retrospectivos , Neoplasias de la Boca/cirugía , Boca/cirugíaRESUMEN
The saponin-enriched extract from Celosiae Semen is a promising resource owing to its lipid-lowering activity. However, triterpenoid saponins are difficult to extract owing to their high molecular weight and strong water solubility. The aim of this paper was to explore an eco-friendly and effective technology of extraction and enrichment of total triterpenoid saponins to obtain high lipid-lowering fractions. Initially, Box-Behnken design experiments were employed to optimize the heat reflux extraction process on the basic of mono-factor experiments. Afterwards, the crude extract was further purified using D-101 resin, and the purification parameters were investigated based on adsorption/desorption experiments and biological activity assay. Under optimal conditions, the purity of the finally obtained total triterpenoid saponins was increased by 7.28-fold. The lipid-lowering activities of the six main triterpenoid saponins were evaluated in HepG2 cells induced by palmitic acid. The results of Oil Red O staining showed that the compounds all exhibited potential lipid-lowering activity. The structure-activity relationship analysis suggested that the oligosaccharide chain at C-28 played an essential role in their lipid-lowering activity and the substituent group at C-23 site also showed important effects. The optimal extraction and purification methods may facilitate the utilization of Celosiae Semen for the industrial production as a functional food and drug.
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Amaranthaceae , Metabolismo de los Lípidos , Saponinas/química , Saponinas/farmacología , Triterpenos/química , Amaranthaceae/química , Extractos Vegetales/química , Extractos Vegetales/farmacología , Metabolismo de los Lípidos/efectos de los fármacos , Humanos , Células Hep G2 , Etanol/químicaRESUMEN
Radical prostatectomy is a primary treatment option for localized prostate cancer (PCa), although high rates of recurrence are commonly observed postsurgery. Photodynamic therapy (PDT) has demonstrated efficacy in treating nonmetastatic localized PCa with a low incidence of adverse events. However, its limited efficacy remains a concern. To address these issues, various organic polymeric nanoparticles (OPNPs) loaded with photosensitizers (PSs) that target prostate cancer have been developed. However, further optimization of the OPNP design is necessary to maximize the effectiveness of PDT and improve its clinical applicability. This Review provides an overview of the design, preparation, methodology, and oncological aspects of OPNP-based PDT for the treatment of PCa.
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SLC7A11 is a unit of the glutamate cystine antiporter Xc- system. It functions to import cystine for glutathione biosynthesis and maintains the redox balance in cells. Sorafenib inhibits the transporter activity of SLC7A11. The use of sorafenib has been approved in the treatment of multiple cancers. However, at present, our understanding of the mechanism of SLC7A11 and sorafenib in nasopharyngeal carcinoma (NPC) remains limited. We found that the expression of SLC7A11 was upregulated in NPC. A high SLC7A11 expression was associated with poor prognosis, metastasis, and an advanced T stage, which can be used as an independent prognostic indicator of NPC. In vitro, we observed that NPC cells relied on cystine for survival. Targeting SLC7A11 resulted in glutathione biosynthesis limitation, intracellular reactive oxygen species accumulation, lipid peroxides, ferroptosis, and apoptosis. Meanwhile, it altered mitogen activated protein kinase pathway, including p38 activation but ERK inhibition in NPC. This limited the proliferation of NPC cells. Sorafenib inhibited the proliferation and induced the death of NPC cells in vivo. In conclusion, SLC7A11 plays an important role in the occurrence and progression of NPC and may be a novel target for NPC treatment.
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Ferroptosis , Neoplasias Nasofaríngeas , Humanos , Carcinoma Nasofaríngeo , Sorafenib/farmacología , Proteínas Quinasas Activadas por Mitógenos/metabolismo , Cistina/metabolismo , Apoptosis , Glutatión/metabolismo , Neoplasias Nasofaríngeas/tratamiento farmacológico , Neoplasias Nasofaríngeas/genética , Sistema de Transporte de Aminoácidos y+/genética , Sistema de Transporte de Aminoácidos y+/metabolismoRESUMEN
BACKGROUND: We aimed to unbiasedly map the genetic mutation profile of HNSC and CESC associated with HPV status in the Chinese population (SYSU-cohort) and compare them with Western population (TCGA-cohort). METHODS: Fifty-one HNSC patients (SYSU-HNSC) and 38 CESC patients (SYSU-CESC) were enrolled in this study. Genomic alterations were examined, and the profile was produced using the YuanSuTM450 gene panel (OrigiMed, Shanghai, China). The altered genes were inferred and compared to Western patients from TCGA cohorts. RESULTS: Compared to the TCGA-HNSC cohort, FGFR3 mutation was identified as a novel target in SYSU-HNSC with therapeutic potential. Compared to the TCGA-CESC cohort, some epigenetic regulation-associated genes were frequently mutated in SYSU-CESC cohort (KMT2C, KMT2D, KDM5C, KMT2A). CONCLUSION: In summary, our study provides unbiased insights into the genetic landscape of HNSC and CESC in the Chinese population and highlights potential novel therapeutic targets that may benefit Chinese patients.
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Neoplasias de Cabeza y Cuello , Neoplasias del Cuello Uterino , Femenino , Humanos , Neoplasias del Cuello Uterino/genética , Epigénesis Genética , China , Neoplasias de Cabeza y Cuello/genética , MutaciónRESUMEN
The poor efficacy of chimeric antigen receptor T-cell therapy (CAR T) for solid tumors is due to insufficient CAR T cell tumor infiltration, in vivo expansion, persistence, and effector function, as well as exhaustion, intrinsic target antigen heterogeneity or antigen loss of target cancer cells, and immunosuppressive tumor microenvironment (TME). Here we describe a broadly applicable nongenetic approach that simultaneously addresses the multiple challenges of CAR T as a therapy for solid tumors. The approach reprograms CAR T cells by exposing them to stressed target cancer cells which have been exposed to the cell stress inducer disulfiram (DSF) and copper (Cu)(DSF/Cu) plus ionizing irradiation (IR). The reprogrammed CAR T cells acquire early memory-like characteristics, potent cytotoxicity, enhanced in vivo expansion, persistence, and decreased exhaustion. Tumors stressed by DSF/Cu and IR also reprogram and reverse the immunosuppressive TME in humanized mice. The reprogrammed CAR T cells, derived from peripheral blood mononuclear cells of healthy donors or metastatic female breast cancer patients, induce robust, sustained memory and curative anti-solid tumor responses in multiple xenograft mouse models, establishing proof of concept for empowering CAR T by stressing tumor as a promising therapy for solid tumors.
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Neoplasias de la Mama , Receptores Quiméricos de Antígenos , Humanos , Femenino , Animales , Ratones , Leucocitos Mononucleares , Microambiente Tumoral , Neoplasias de la Mama/terapia , Modelos Animales de Enfermedad , Inmunosupresores , Linfocitos TRESUMEN
BACKGROUND: The trend in postoperative care for free flap patients is to deescalate from routine ICU admission into a specialty recovery unit. This study aims to investigate the predictive parameters in a routine perioperative clinical assessment that are expected to be directly correlated with prolonged ICU length of stay in at-risk patients who received oral reconstructive surgery for squamous cell carcinoma (OSCC). METHODS: All patients who underwent ablative surgery for OSCC with free flap reconstruction and were managed in the ICU were included in this study. The primary outcome was ICU-length of stay. Perioperative, operative and postoperative parameters were analyzed using single test ( t-test, ANOVA analysis, correlation coefficients, effect size) and multivariate regression test. The P-value was set as < 0.005 to be considered statically significant. RESULTS: The study included 136 homogeneous patients, with a mean ICU length of stay of 4.5 (± 4.43 day). Patients with pre-operative positive renal dysfunction (P = 0.004), peripheral vascular disease (P < 0.001), postoperative complications (P = 0.028) or positive heart failure class III (P < 0.001 ) were recognized as at-risk patients for a significantly longer ICU length of stay. CONCLUSION: Patients with perioperative severe renal dysfunction, peripheral vascular disease, postoperative complication or high NYHA class are prone to have a significantly longer ICU length of stay. Several factors were considered as confounders contributing to increased ICU management time in combination with other variables. Additionally, in highly risk patient, the presence of the highly trained medical support, including the appropriate nursing care, is more critical than those patients without these risk factors.
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Carcinoma de Células Escamosas , Neoplasias de Cabeza y Cuello , Enfermedades Renales , Neoplasias de la Boca , Enfermedades Vasculares Periféricas , Humanos , Carcinoma de Células Escamosas/cirugía , Carcinoma de Células Escamosas de Cabeza y Cuello , Tiempo de Internación , Neoplasias de la Boca/cirugía , Unidades de Cuidados Intensivos , Complicaciones Posoperatorias , Factores de RiesgoRESUMEN
BACKGROUND: This study aimed to determine the correlation between human-immunodeficiency-virus (HIV) infection and stroke, as well as to estimate the global, regional, and national burden of HIV-associated stroke. METHODS: A registered meta-analysis was performed by searching PubMed, Embase, and Web of Science for relevant literature up to October 31, 2022. The pooled relative risk of stroke in HIV-infected people was calculated using a random-effects model. HIV prevalence and disability-adjusted life years (DALYs) datasets were obtained from the Joint United Nations Program on HIV and AIDS, and the Global Health Data Exchange, respectively. The population attributable fraction was estimated and delivered to calculate the HIV-associated DALYs of stroke from 1990 to 2019, at the global, regional, and national levels. Pearson correlation analysis were conducted to assess the correlation between the age-standardized rate or estimated annual percentage changes and the sociodemographic index. RESULTS: Out of 10â 080 identified studies, 11 were included in this meta-analysis. Compared with individuals without HIV-infection, the pooled relative risk of stroke in HIV-infected individuals was 1.40 (95% CI, 1.18-1.65). From 1990 to 2019, the global population attributable fraction of HIV-associated stroke increased almost 3-fold, while the HIV-associated DALYs increased from 18 595 (95% CI, 7485-31â 196) in 1990 to 60â 684 (95% CI, 24â 281-101â 894) in 2019. Meanwhile, HIV-associated DALYs varied by region, with Eastern and Southern Africa having the highest value of 126â 160 in 2019. Moreover, countries with middle social development index were shouldering the highest increase trend of the HIV-associated DALYs age-standardized rates. CONCLUSIONS: HIV-infected individuals face a significantly higher risk of stroke, and the global burden of HIV-associated stroke has increased over the past 3 decades, showing regional variations. Eastern and Southern Africa bear the highest burden, while Eastern Europe and Central Asia have seen significant growth. Health care providers, researchers, and decision-makers should give increased attention to stroke prevention and management in HIV-endemic areas. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: CRD42022367450.
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Infecciones por VIH , Accidente Cerebrovascular , Humanos , Años de Vida Ajustados por Calidad de Vida , Accidente Cerebrovascular/epidemiología , Infecciones por VIH/complicaciones , Infecciones por VIH/epidemiología , Salud Global , Proyectos de Investigación , Carga Global de Enfermedades , Factores de RiesgoRESUMEN
Introduction: The health and economic benefits of human papillomavirus (HPV) vaccination targeted at men who have sex with men (MSM) in developing settings have been rarely assessed. This study aimed to evaluate the effectiveness and cost-effectiveness of different HPV vaccination strategies among MSM in China. Methods: A Markov model was developed to simulate HPV transmission dynamics among a total of 30.73 million MSM in China. The corresponding natural history included 6 states: susceptible, infected with low-risk subtypes, high-risk subtypes, anogenital warts and anal cancer, and deaths from anal cancer. MSM were divided into three age groups with cut-off points of 27 and 45 years. Alternative vaccination strategies were built by allocating bivalent, quadrivalent, nine-valent, or no vaccine to each of the groups. We generated the prevented infections and deaths by vaccination compared with baseline (no vaccination) and calculated incremental cost-effectiveness ratios (ICERs) to determine the optimal strategy. Results: The model showed that in 10 years, at baseline, the existing cases of anogenital warts would reach 5,464,225 (IQR, 4,685,708-6,174,175); that of anal cancer would reach 1,922.95 (1,716.56-2,119.93), resulting in 940.55 (732.27-1,141.87) deaths. Under 50% vaccination coverage among one age group, the prevented cases of anogenital warts were maximized with quadrivalent vaccines allocated to MSM aged 27-45 years; that of anal cancer were maximized when offering nine-valent vaccines to the same group. Under 50% vaccination coverage among all groups, the lowest ICER (34,098.09 USD/QALY, 31,146.54-37,062.88) was reached when only quadrivalent vaccines were provided. Based on this strategy, when the annual vaccination rate increased by 30%, the ICER (33,521.75 USD/QALY, 31,040.73-36,013.92) would fall below three times China's per capita GDP. When the vaccine price decreased by 60%, the ICER was reduced to 7,344.44 USD/QALY (4,392.89-10,309.23), indicating good cost-effectiveness taking China's per capita GDP as a threshold. Conclusions: HPV vaccination can effectively reduce the prevalence and mortality of related diseases among MSM in China, especially quadrivalent vaccines for anogenital warts and nine-valent vaccines for anal cancer. MSM aged 27-45 years were the optimal group for vaccination. Annual vaccination and appropriate adjustment of vaccine price are necessary to further improve the cost-effectiveness.
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Neoplasias del Ano , Condiloma Acuminado , Infecciones por Papillomavirus , Vacunas contra Papillomavirus , Minorías Sexuales y de Género , Masculino , Humanos , Homosexualidad Masculina , Infecciones por Papillomavirus/epidemiología , Infecciones por Papillomavirus/prevención & control , Virus del Papiloma Humano , Análisis Costo-Beneficio , Condiloma Acuminado/epidemiología , Condiloma Acuminado/prevención & control , Vacunas Combinadas , Neoplasias del Ano/epidemiología , Neoplasias del Ano/prevención & controlRESUMEN
A retrospective study was performed on 200 patients who underwent miniaturized percutaneous nephrolithotomy (mini-PCNL) or retrograde intrarenal surgery (RIRS) for 10-20 mm sized lower pole renal calculi to investigate the relationship between computed tomography (CT) attenuation of calculi and surgical outcomes. CT was used to examine the location, size, and CT attenuation values of the calculi. Additionally, the operation time, hospital stay, hemoglobin (Hb) reduction, stone-free rate (SFR), and complication rate were also meticulously documented and subjected to comparative analysis. Complications were assessed using the Clavien-Dindo grading system. We observed no significant differences in hospitalization data and follow-up outcomes, except for a longer hospital stay and higher Hb drops in patients receiving mini-PCNL. Statistical analysis revealed an association between CT attenuation and operation time. Compared with mini-PCNL, RIRS could reduce bleeding, hospital stay, surgery time, and complications for 10-20 mm sized lower pole kidney stones with CT values < 1000 HU. RIRS resulted in longer operation time and lower stone-free rates despite shorter hospital stays and less bleeding than mini-PCNL for stones with CT values > 1000 HU. Therefore, selecting an appropriate surgical method based on CT attenuation might improve outcomes. For patients with stone attenuation values < 1000 HU, RIRS is the recommended option. When stone attenuation values > 1000 HU, the surgical method should be chosen based on the patient's individual situation.
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Cálculos Renales , Nefrolitotomía Percutánea , Nefrostomía Percutánea , Cirujanos , Humanos , Nefrolitotomía Percutánea/métodos , Estudios Retrospectivos , Nefrostomía Percutánea/efectos adversos , Cálculos Renales/cirugía , Tomografía Computarizada por Rayos X , Resultado del TratamientoRESUMEN
The poor efficacy of chimeric antigen receptor T-cell therapy (CAR T) for solid tumor is due to insufficient CAR T cell tumor infiltration, in vivo expansion, persistence, and effector function, as well as exhaustion, intrinsic target antigen heterogeneity or antigen loss of target cancer cells, and immunosuppressive tumor microenvironment (TME). Here we describe a broadly applicable nongenetic approach that simultaneously addresses the multiple challenges of CAR T as a therapy for solid tumors. The approach massively reprograms CAR T cells by exposing them to stressed target cancer cells which have been exposed to the cell stress inducer disulfiram (DSF) and copper (Cu)(DSF/Cu) plus ionizing irradiation (IR). The reprogrammed CAR T cells acquired early memory-like characteristics, potent cytotoxicity, enhanced in vivo expansion, persistence, and decreased exhaustion. Tumors stressed by DSF/Cu and IR also reprogrammed and reversed immunosuppressive TME in humanized mice. The reprogrammed CAR T cells, derived from peripheral blood mononuclear cells (PBMC) of healthy or metastatic breast cancer patients, induced robust, sustained memory and curative anti-solid tumor responses in multiple xenograft mouse models, establishing proof of concept for empowering CAR T by stressing tumor as a novel therapy for solid tumor.
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KEY MESSAGE: The resistance of Huaidao5 results from the high constitutive expression of tolerance genes, while that of Huaidao9 is due to the cold-induced resistance in flag leaves and panicles. The regulation mechanism of rice seedlings' cold tolerance is relatively clear, and knowledge of its underlying mechanisms at the reproductive stage is limited. We performed differential expression and co-expression network analyses to transcriptomes from panicle and flag leaf tissues of a cold-tolerant cultivar (Huaidao5), and a sensitive cultivar (Huaidao9), under reproductive-stage cold stress. The results revealed that the expression levels of genes in stress-related pathways such as MAPK signaling pathway, diterpenoid biosynthesis, glutathione metabolism, plant-pathogen interaction and plant hormone signal transduction were constitutively highly expressed in Huaidao5, especially in panicles. Moreover, the Hudaidao5's panicle sample-specific (under cold) module contained some genes related to rice yield, such as GW5L, GGC2, SG1 and CTPS1. However, the resistance of Huaidao9 was derived from the induced resistance to cold in flag leaves and panicles. In the flag leaves, the responses included a series of stress response and signal transduction, while in the panicles nitrogen metabolism was severely affected, especially 66 endosperm-specific genes. Through integrating differential expression with co-expression networks, we predicted 161 candidate genes (79 cold-responsive genes common to both cultivars and 82 cold-tolerance genes associated with differences in cold tolerance between cultivars) potentially affecting cold response/tolerance, among which 85 (52.80%) were known to be cold-related genes. Moreover, 52 (65.82%) cold-responsive genes (e.g., TIFY11C, LSK1 and LPA) could be confirmed by previous transcriptome studies and 72 (87.80%) cold-tolerance genes (e.g., APX5, OsFbox17 and OsSTA109) were located within QTLs associated with cold tolerance. This study provides an efficient strategy for further discovery of mechanisms of cold tolerance in rice.
Asunto(s)
Respuesta al Choque por Frío , Oryza , Respuesta al Choque por Frío/genética , Transcriptoma/genética , Oryza/metabolismo , Genotipo , Perfilación de la Expresión Génica , Regulación de la Expresión Génica de las Plantas/genética , FríoRESUMEN
Barley bran has potential bioactivities due to its high content of polyphenols and dietary fiber, etc. Fermentation has been considered as an effective way to promote the functional activity of food raw materials. In this study, polysaccharides from barley bran extract fermented by Lactiplantibacillus plantarum dy-1 (FBBE-PS) were analyzed, and its effects on lipid accumulation and oxidative stress in high-fat HepG2 cells induced by sodium oleate were evaluated. The results showed that the molecular weight decreased and monosaccharide composition of polysaccharides changed significantly after fermentation. In addition, 50 µg/mL FBBE-PS could reduce the triglyceride (TG) content and reaction oxygen species (ROS) level in high-fat HepG2 cells by 21.62% and 30.01%, respectively, while increasing the activities of superoxide dismutase (SOD) and catalase (CAT) represented by 64.87% and 22.93%, respectively. RT-qPCR analysis revealed that FBBE-PS could up-regulate the lipid metabolism-related genes such as ppar-α, acox-1 and cpt-1α, and oxidation-related genes such as nrf2, ho-1, nqo-1, sod1, cat, etc. The metabolomics analysis indicated that FBBE-PS could alleviate lipid deposition by inhibiting the biosynthesis of unsaturated fatty acids, which is consistent with the downregulation of scd-1 expression. It is demonstrated that fermentation can alter the properties and physiological activities of polysaccharides in barley bran, and FBBE-PS exhibited an alleviating effect on lipid deposition and oxidative stress in high-fat cells.
RESUMEN
Clear cell renal cell carcinoma (ccRCC) has a high metastatic rate, and its incidence and mortality are still rising. The aim of this study was to identify the key tumor-infiltrating immune cells (TIICs) affecting the distant metastasis and prognosis of patients with ccRCC and to construct a relevant prognostic panel to predict immunotherapy response. Based on ccRCC bulk RNA sequencing data, resting mast cells (RMCs) were screened and verified using the CIBERSORT algorithm, survival analysis, and expression analysis. Distant metastasis-associated genes were identified using single-cell RNA sequencing data. Subsequently, a three-gene (CFB, PPP1R18, and TOM1L1) panel with superior distant metastatic and prognostic performance was established and validated, which stratified patients into high- and low-risk groups. The high-risk group exhibited lower infiltration of RMCs, higher tumor mutation burden (TMB), and worse prognosis. Therapeutically, the high-risk group was more sensitive to anti-PD-1 and anti-CTLA-4 immunotherapy, whereas the low-risk group displayed a better response to anti-PD-L1 immunotherapy. Furthermore, two immune clusters revealing distinct immune, clinical, and prognosis heterogeneity were distinguished. Immunohistochemistry of ccRCC samples verified the expression patterns of the three key genes. Collectively, the prognostic panel based on RMCs is able to predict distant metastasis and immunotherapy response in patients with ccRCC, providing new insight for the treatment of advanced ccRCC.