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Objective: This study aims to develop risk prediction models for neck and shoulder musculoskeletal disorders among healthcare professionals. Methods: A stratified sampling method was employed to select employees from medical institutions in Nanning City, yielding 617 samples. The Boruta algorithm was used for feature selection, and various models, including Tree-Based Models, Single Hidden-Layer Neural Network Models (MLP), Elastic Net Models (ENet), and Support Vector Machines (SVM), were applied to predict the selected variables, utilizing SHAP algorithms for individual-level local explanations. Results: The SVM model excels in both Mean Absolute Error (MAE) and Root Mean Square Error (RMSE) and exhibits more stable performance when generalizing to unseen data. The Random Forest model exhibited relatively high overall performance on the training set. The MLP model emerges as the most consistent and accurate in predicting shoulder musculoskeletal disorders, while the SVM model shows strong fitting capabilities during the training phase, with occupational factors identified as the main contributors to WMSDs. Conclusion: This study successfully constructs work-related musculoskeletal disorder risk prediction models for healthcare professionals, enabling a quantitative analysis of the impact of occupational factors. This advancement is beneficial for future economical and convenient work-related musculoskeletal disorder screening in healthcare professions.
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Personal de Salud , Aprendizaje Automático , Enfermedades Musculoesqueléticas , Enfermedades Profesionales , Humanos , Personal de Salud/estadística & datos numéricos , Enfermedades Musculoesqueléticas/epidemiología , Enfermedades Profesionales/epidemiología , Masculino , Femenino , Adulto , Persona de Mediana Edad , Máquina de Vectores de Soporte , Factores de Riesgo , Medición de Riesgo/métodos , Algoritmos , HombroRESUMEN
Introduction: In the aftermath of the COVID-19 pandemic, the reintegration of Chinese international student returnees intersects with China's critical effort to combat a significant brain drain of highly skilled talents, highlighting an unprecedented psychological battleground. This convergence underscores the urgent need for nuanced research to navigate the uncharted territory of their mental health. Methods: Employing Bayesian analysis supported by Markov Chain Monte Carlo (MCMC) algorithms, this study examined depression prevalence and associated factors among 1,014 Chinese returnees. The sample comprised 44.87% male participants (455), 51.58% female participants (523), and 3.55% identifying as "Others" (36), with an age distribution of 61.74% aged 18-30 (626), 28.80% aged 31-40 (292), and 9.47% aged 41-50 (96). The mean age of participants was 29.6 years, ranging from 18 to 50 years. PHQ-9 diagnoses revealed alarming levels of depression, with 47.9% exhibiting a moderately severe degree of depressive disorder. Results: Our findings highlight the intricate interplay between identity clusters- "homestayers" (those leaning towards a Chinese cultural identity), "navigators" (those with a bicultural identity), and "wayfarers" (those leaning towards a foreign cultural identity)-and the likelihood of depression. Specifically, homestayers showed a clear and strong negative association, navigators demonstrated a positive association, and wayfarers had a positive yet unclear correlation with depression levels. Furthermore, acculturation, age, and gender showed no significant effects, whereas education mildly mitigated depression. Discussion: Based on these findings, we suggest the implementation of better-tailored mental health support and policies to facilitate smoother reintegration.
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In 2021, China's domestically produced coronavirus disease 2019 (COVID-19) vaccines received approval from regulatory bodies and were administered worldwide. Due to a low number of infections within China during that period, it became imperative to evaluate the vaccines' real-world effectiveness through international studies. To facilitate this, China CDC launched the COVID-19 Vaccines Evaluation Program (COVEP). This program formed research collaboration agreements with health institutes across five World Health Organization regions, addressing key questions about vaccine performance through ten cooperative agreements. The findings from COVEP projects reinforced confidence, both domestically and globally, in the effectiveness of the vaccines produced in China. Moreover, the outcomes observed internationally were frequently mirrored by later studies conducted within China. COVEP thus pioneered a novel approach for fostering cross-national research collaborations, addressing significant public health issues and exemplifying a framework for international cooperation. This approach is in line with the strategic objectives and other development efforts of China CDC's national disease control and prevention initiatives.
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Background: Several COVID-19 vaccines were developed and approved in China. Of these, the BIBB-CorV and CoronaVac inactivated whole-virion vaccines were widely distributed in China and developing countries. However, the performance of the two vaccines in the real world has not been summarized. Methods: A living systematic review based on findings from ongoing post-licensure studies was conducted, applying standardized algorithms. Articles published between 1 May 2020 and 31 May 2022 in English and Chinese were searched for in Medline, Embase, WanFang Data, medRxiv, bioRxiv, arXiv, SSRN, and Research Square, using SARS-CoV-2, COVID-19, and vaccine as the MeSH terms. Studies with estimates of safety, immunogenicity, and effectiveness from receiving the BIBB-CorV or CoronaVac vaccine that met the predefined screening criteria underwent a full-text review. The Joanna Briggs Institute's Critical Appraisal Checklist and the Cochrane risk of bias were used for assessment of the quality. A random-effects meta-regression model was applied to identify the potential impact factors on the vaccines' effectiveness. Results: In total, 32578 articles were identified, of these, 770 studies underwent a full-text review. Eventually, 213 studies were included. The pooled occurrence of solicited and unsolicited adverse events after any dose of either vaccine varied between 10% and 40%. The top five commonly reported rare adverse events were immunization stress-related responses (211 cases, 50.0%), cutaneous responses (43 cases, 10.2%), acute neurological syndrome (39 cases, 9.2%), anaphylaxis (17 cases, 4.0%), and acute stroke (16 cases, 3.8%). The majority (83.3%) recovered or were relieved within several days. The peak neutralization titers against the ancestral strain was found within 1 month after the completion of the primary series of either vaccine, with a GMT (geometric mean titer) of 43.7 (95% CI: 23.2-82.4), followed by a dramatic decrease within 3 months. At Month 12, the GMT was 4.1 (95% CI: 3.8-4.4). Homologous boosting could restore humoral immunity, while heterologous boosting elicited around sixfold higher neutralization titers in comparison with homologous boosting. The effectiveness of receiving either vaccine against death and severe disease was around 85% for both shortly after the primary series. At Month 12, the protection against death did not decline, while the protection against severe disease decreased to ~75%. Conclusions: Both the BIBP-CorV and CoronaVac inactivated vaccines are safe. Sustained vaccine effectiveness against death was determined 12 months after the primary series, although protection against severe disease decreased slightly over time. A booster dose could strengthen the waning effectiveness; however, the duration of the incremental effectiveness and the additional benefit provided by a heterologous booster need to be studied.
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The Immunization and Vaccine-related Implementation Research Advisory Committee (IVIR-AC) is the World Health Organization's key standing advisory body to conduct an independent review of research, particularly of transmission and economic modeling analyses that estimate the impact and value of vaccines. From 26th February-1st March 2024, at its first of two semi-annual meetings, IVIR-AC provided feedback and recommendations across four sessions; this report summarizes the proceedings and recommendations from that meeting. Session topics included modeling of the impact and cost-effectiveness of the R21/Matrix-M malaria vaccine, meta-analysis of economic evaluations of vaccines, a global analysis estimating the impact of vaccination over the last 50 years, and modeling the impact of different RTS,S malaria vaccine dose schedules in seasonal settings.
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Comités Consultivos , Vacunas contra la Malaria , Organización Mundial de la Salud , Humanos , Vacunas contra la Malaria/administración & dosificación , Vacunas contra la Malaria/inmunología , Análisis Costo-Beneficio , Vacunación/métodos , Malaria/prevención & control , Inmunización/métodosRESUMEN
Dopamine and norepinephrine are implicated in the pathophysiology of mental disorders, but non-invasive study of their neuronal function remains challenging. Recent research suggests that neuromelanin-sensitive magnetic resonance imaging (NM-MRI) techniques may overcome this limitation by enabling the non-invasive imaging of the substantia nigra (SN)/ ventral tegmental area (VTA) dopaminergic and locus coeruleus (LC) noradrenergic systems. A review of 19 studies that met the criteria for NM-MRI application in mental disorders found that despite the use of heterogeneous sequence parameters and metrics, nearly all studies reported differences in contrast ratio (CNR) of LC or SN/VTA between patients with mental disorders and healthy controls. These findings suggest that NM-MRI is a valuable tool in psychiatry, but the differences in sequence parameters across studies hinder comparability, and a standardized analysis pipeline is needed to improve the reliability of results. Further research using standardized methods is needed to better understand the role of dopamine and norepinephrine in mental disorders.
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Imagen por Resonancia Magnética , Melaninas , Trastornos Mentales , Humanos , Melaninas/metabolismo , Trastornos Mentales/diagnóstico por imagen , Trastornos Mentales/metabolismo , Imagen por Resonancia Magnética/métodos , Locus Coeruleus/diagnóstico por imagen , Locus Coeruleus/metabolismo , Sustancia Negra/diagnóstico por imagen , Sustancia Negra/metabolismo , Norepinefrina/metabolismoRESUMEN
PURPOSE: Breast cancer (BC) is diagnosed as the most common cancer in women in 2022 according to the American Cancer Society. It is essential to detect early and treat early. Several studies have shown that some blood parameters have important predictive value for BC. In this study, we aim to explore whether some immune-associated blood parameters are relevant to disease-free survival (DFS) in early-stage BC. METHODS: A single-center, regression cohort study of 1490 patients with early-stage BC in Shanghai Cancer Center was conducted from January 2008 to December 2016. The patients were matched according to the ratio of 1:1 based on Propensity Score Matching (PSM). All patients who experienced disease progression were matched successfully. Thus, 58 pairs of subjects were obtained. Matched blood parameters were evaluated by paired samples t-test or Wilcoxon signed-rank test. Factors with statistical difference were further evaluated by stratified COX regression model. RESULTS: Univariate analysis showed differences in platelet-related parameters (PLT, PCT, and PLR) and NLR between the two matched groups. However, stratified COX regression analysis, which ruled out the confounding effects of multiple factors, found that only PCT had prognostic value in early BC patients at baseline and study endpoint. Meanwhile, platelet-related parameters (PLT, MPV) and NLR were different in the progressive group by self before and after comparison. However, the multiple-factor analysis showed that only the NLR had prognostic value. ROC curve analysis indicated that the best sensitivity (65.45%) and specificity (78.18%) were obtained when the baseline PCT was 0.225. The optimal sensitivity (70.91%) and specificity (65.45%) were obtained when the PCT of disease progression was 0.215. The Kaplan-Meier curve was used to calculate the DFS rate based on the critical values of the two groups. CONCLUSIONS: Some blood parameters have value to predict DFS in early-stage BC patients, especially platelet-associated parameters.
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Plaquetas , Neoplasias de la Mama , Humanos , Femenino , Neoplasias de la Mama/diagnóstico , Neoplasias de la Mama/terapia , Estudios de Cohortes , Estudios Retrospectivos , Puntaje de Propensión , China/epidemiología , Pronóstico , Recuento de Plaquetas , Progresión de la Enfermedad , Neutrófilos , LinfocitosRESUMEN
AIM: The objective of this study is to comprehensively evaluate the therapeutic efficacy of postmastectomy radiotherapy (PMRT) in treating patients with pT3N0-1M0 breast cancer within the context of modern therapeutic strategies. METHODS: Clinical data from patients with pT3N0-1M0 breast cancer who underwent mastectomy from January 2005 to December 2018 at our institution were retrospectively analyzed. RESULTS: The study involved a total of 222 participants, with 112 individuals undergoing PMRT and 110 individuals not receiving it. The median follow-up duration was 77 months (range: 6-171 months). The entire cohort demonstrated 5-year disease-free survival (DFS) and overall survival (OS) rates of 85.1% and 91.0%, respectively, along with a locoregional recurrence (LRR) rate as low as 7.2%. The PMRT group showed significantly better 5-year DFS (90.2% vs. 80.0%, p = 0.02) and OS (95.5% vs. 86.4%, p = 0.012) rates, as well as a lower LRR rate (4.5% vs. 10.0%, p = 0.122), compared to the group without PMRT. Cox regression analysis confirmed the independent prognostic significance of PMRT for both DFS (p = 0.040) and OS (p = 0.047). Following propensity score matching (PSM), the analysis included 100 matched patients, revealing an improved prognosis for those who received PMRT (DFS: p = 0.067; OS: p = 0.043). CONCLUSIONS: Our study reveals favorable prognoses for pT3N0-1M0 breast cancer patients treated within contemporary therapeutic approaches. The pivotal role of PMRT in this context is evident. However, due to the retrospective design of our study and the relatively limited sample size, further investigation is imperative to validate and enhance these initial findings.
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Neoplasias de la Mama , Mastectomía , Recurrencia Local de Neoplasia , Humanos , Femenino , Neoplasias de la Mama/radioterapia , Neoplasias de la Mama/cirugía , Neoplasias de la Mama/patología , Neoplasias de la Mama/mortalidad , Persona de Mediana Edad , Estudios Retrospectivos , Radioterapia Adyuvante/métodos , Adulto , Anciano , Estadificación de Neoplasias , Resultado del Tratamiento , Supervivencia sin EnfermedadRESUMEN
Underutilization of mental health services is common and associated with substantial suffering, mental disorders and death. The present study aimed to explore factors significantly affecting the professional psychological help-seeking behavior based on the Theory of Planned Behavior (TPB). A sample of 597 Chinese college students recruited online completed the questionnaires, which measured four constructs of TPB including help-seeking intention, attitude, subjective norm and perceived behavioral control in December 2020. Help-seeking behaviors were evaluated three months later in March 2021. A two-step structural equation modeling procedure was used to test the TPB model. Findings show that partially consistent with TPB, more positive attitudes about seeking professional help (Β = .258, p = .001) and higher perceived behavioral control (Β = .504, p < .001) directly predicted higher intention to seek mental health services, and perceived behavioral control (Β = .230, p = .006) directly predicted help-seeking behavior. However, behavioral intention (Β = -.017, p = .830) did not statistically significantly predict help-seeking behavior, while subjective norm (Β = .047, p = .356) did not predict help-seeking intention as well. The model accounted for 49.9% of the variance modeling help-seeking intention and 12.4% of the variance modeling help-seeking behavior. The results revealed the importance of attitude and perceived behavioral control in predicting help-seeking intention and behavior among Chinese college students and indicated that there existed a gap between intention and actual help-seeking behavior.
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Intención , Teoría del Comportamiento Planificado , Humanos , Estudios de Seguimiento , Actitud , Encuestas y Cuestionarios , Estudiantes/psicología , Teoría PsicológicaRESUMEN
Recently, hydrogen spillover based binary (HSBB) catalysts have received widespread attention due to the sufficiently utilized reaction sites. However, the specific regulation mechanism of spillover intensity is still unclear. Herein, we have fabricated oxygen vacancies enriched Ru/NiMoO4-x to investigate the internal relationship between electron supply and mechanism of hydrogen spillover enhancement. The DFT calculations cooperate with in situ Raman spectrum to uncover that the H* spillover from NiMoO4-x to Ru. Meanwhile, oxygen vacancies weakened the electron supply from Ru to NiMoO4-x , which contributes to dilute the resistance of built-in electric field (BEF) for hydrogen spillover. In addition, the higher ion concentration in electrolyte will promote the H* adsorption step obviously, which is demonstrated by in situ EIS tests. As a result, the Ru/NiMoO4-x exhibits a low overpotential of 206â mV at 3.0â A cm-2 , a small Tafel slope of 28.8â mV dec-1 , and an excellent durability of 550â h at the current density of 0.5â A cm-2 for HER in 1.0â M KOH seawater.
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Due to the shortage of pure water resources, seawater electrolysis is a promising strategy to produce green hydrogen energy. To avoid chlorine oxidation reactions (ClOR) and the production of more corrosive hypochlorite, enhancing OER electrocatalyst activity is the key to solving the above problem. Considering that transition metal phosphides (TMPs) are promising OER eletrocatalysts for seawater splitting, a method to regulate the electronic structure of FeP by introducing Mn heteroatoms and phosphorus vacancy on it (Mn-FePV ) is developed. As an OER electrocatalyst in seawater solution, the synthesized Mn-FePV achieves extremely low overpotentials (η500 = 376, η1000 = 395 mV). In addition, the Pt/C||Mn-FePV couple only requires the voltage of 1.81 V to drive the current density of 1000 mA cm-2 for overall seawater splitting. The density functional theory (DFT) calculation shows that Mn-FePV (0.21 e- ) has more charge transfer number compared with FeP (0.17 e- ). In-situ Raman analysis shows that phosphorus vacancy and Mn doping can synergistically regulate the electronic structure of FeP to induce rapid phase reconstruction, further improving the OER performance of Mn-FePV . The new phase species of FeOOH is confirmed to can enhance the adsorption kinetics of OER intermediates.
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Acute gastroenteritis (AGE) caused by rotavirus (RV) remains a public health issue in China. To accelerate the mass rotavirus vaccination, it is important to inform the policy maker, and the public of the economic burden caused by rotavirus infection. A meta-analysis was conducted applying standardized algorithms. Articles published before January 1, 2023, in English and Chinese were searched through PubMed, CNKI, and WanFang Data. Studies with cost analysis of RV AGE were included. A random-effects model was applied to synthesize the total cost of RV AGE from the societal perspective. A prospective survey aimed to measure the cost of RV AGE was conducted in 2021 and 2022 in Shaoxing city, Zhejiang province, that can represent the developed region. The cost data was applied as deviation indicator, in comparison with the pooled estimate generated from meta-analysis. Totally 286 articles were identified, and eventually 12 studies were included. The pooled total social cost of RV AGE was US$282.1 (95%CI: US$213.4-350.7). The pooled private cost of RV AGE was US$206.4 (95%CI: US$155.2-257.5). RV AGE hospitalized and RV AGE incurred in developed regions caused remarkable higher burden (US$631.2 [95%CI: US$512.6-749.8], and US$333.6 [95%CI: US$234.1-433.2] respectively), compared to RV AGE treated at outpatient, and incurred in less developed regions. Our study demonstrates that RV AGE causes a significant economic burden in China. Given the promising effectiveness and highly cost-effective, introduction of rotavirus vaccines in national immunization programs could substantially reduce the economic burden in China.
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Gastroenteritis , Infecciones por Rotavirus , Vacunas contra Rotavirus , Humanos , Lactante , Análisis Costo-Beneficio , Pueblos del Este de Asia , Gastroenteritis/epidemiología , Gastroenteritis/prevención & control , Gastroenteritis/virología , Vacunación Masiva , Estudios Prospectivos , Rotavirus , Infecciones por Rotavirus/epidemiología , Infecciones por Rotavirus/prevención & control , PreescolarRESUMEN
BACKGROUND: For some ICU patients, an artificial airway must be established with an endotracheal tube, but Candida albicans can easily adhere to the tube surface and form a biofilm, leading to potentially life threatening fungal infections. Therefore, it is urgent to prevent and reduce C. albicans infections introduced by the endotracheal tube. However, there are few antifungal drugs effective against C. albicans, and each of these drugs may have adverse effects on human cells. Saccharomyces boulardii is regarded as an alternative strategy to inhibit the adhesion of C. albicans, but it is affected by environmental stress. We hypothesized that it is feasible to strengthen the antagonistic ability of S. boulardii via encapsulating and genetically modification. METHODS: In this study, a bioactive material carrying the overexpressed MCP1 gene of Saccharomyces boulardii was constructed based on one-step photo-crosslinking. This material achieved spatial growth control of S. boulardii by encapsulating each S. boulardii cell within a hydrogel pore. The bioactive material was coated on an endotracheal tube and tested for its ability to inhibit the adhesion of C. albicans. Additionally, the material's antagonistic activity towards C. albicans was evaluated by detecting intracellular Adenosine-triphosphate content, reactive oxygen species level and the activity of antioxidative enzymes. Tissue invasion experiment was executed to further evaluate the anti-adhesion ability of S. boulardii bio-coating. RESULTS: Encapsulating the overexpression of MCP1 by S. boulardii in hydrogel pores enhanced the viability of probiotics in the presence of high salt and oxidation stress. When used as the coating of an endotracheal tube, the S. boulardii bioactive material efficiently inhibited the adhesion of C. albicans by impairing the activities of superoxide dismutase and catalase and disturbing mitochondrial functions. In vivo, the S. boulardii bioactive material coating displayed good biocompatibility and reduced the host tissue invasion and virulence of C. albicans. CONCLUSIONS: The integration of genetic modification and immobilization model breaks the bottleneck of previous application of microorganisms, and provides a new way to prevent fungal infections introduced by endotracheal tubes.
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Uromodulin (Umod, Tamm-Horsfall protein) is the most abundant urinary N-glycoprotein produced exclusively by the kidney. It can form filaments to antagonize the adhesion of uropathogens. However, the site-specific N-glycosylation signatures of Umod in healthy individuals and patients with IgA nephropathy (IgAN) remain poorly understood due to the lack of suitable isolation and analytical methods. In this study, we first presented a simple and fast method based on diatomaceous earth adsorption to isolate Umod. These isolated glycoproteins were digested by trypsin and/or Glu-C. Intact N-glycopeptides with or without HILIC enrichment were analyzed using our developed EThcD-sceHCD-MS/MS. Based on the optimized workflow, we identified a total of 780 unique intact N-glycopeptides (7 N-glycosites and 152 N-glycan compositions) from healthy individuals. As anticipated, these glycosites exhibited glycoform heterogeneity. Almost all N-glycosites were modified completely by the complex type, except for one N-glycosite (N275), which was nearly entirely occupied by the high-mannose type for mediating Umod's antiadhesive activity. Then, we compared the N-glycosylation of Umod between healthy controls (n = 9) and IgAN patients (n = 9). The N-glycosylation of Umod in IgAN patients will drastically decrease and be lost. Finally, we profiled the most comprehensive site-specific N-glycosylation map of Umod and revealed its alterations in IgAN patients. Our method provides a high-throughput workflow for characterizing the N-glycosylation of Umod, which can aid in understanding its roles in physiology and pathology, as well as serving as a potential diagnostic tool for evolution of renal tubular function.
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The combination of amendments has emerged as a potential strategy to efficiently alleviate salt stress in saline-alkali soil. However, knowledge regarding how to optimize the proportion of different amendment materials, comprehensively assess the contribution of each component, and clarify the response mechanisms of the amendment-saline-alkali soil-plant system is incomplete. Based on this, we conducted a pot experiment to evaluate the improvement effect of the combined application of different amendment materials at varying levels and the contribution of the amendment components to alleviating salt stress. Overall, T6 exhibited the most significant improvement effect on the physicochemical and biological properties of the saline-alkali soil and promoted the growth of oilseed rape, with the levels of 2.0 % phosphogypsum, 2.0 % humic acid, 0.25 % bentonite, and 0.03 % sodium carboxymethyl cellulose. Compared with the control group, the EC decreased by 1.51 % to 33.49 %, the soil salt content dropped by 11.40 % to 35.46 %, and the soil soluble Na + concentration significantly declined by 39.47 % to 63.20 %. Additionally, the soil nutrient content and soil microbial community structure were enhanced in treatment groups. Meanwhile, amendments alleviated salt stress in the oilseed rape plant by activating anti-oxidative enzymes and osmoregulatory substances such as soluble sugar and proline, thus improving their ability to remove reactive oxygen species (ROS). The anti-oxidative enzymes such as superoxide dismutase (SOD), peroxidase (POD), and catalase (CAT) were significantly increased, with an increase of 10.68 % (SOD, T2) â¼207.31 % (CAT, T6) compared to the control group. The structural equation modeling (SEM) analysis and simulation experiments indicated that the amendment components synergically promoted the amelioration effect on salt stress, and effectively improved soil properties, which affected the response of oilseed rape to soil environment. This research paper provides the relevant reference for the combined application of different amendment materials for soil reclamation.
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Álcalis , Suelo , Suelo/química , Plantas , Sustancias Húmicas , Superóxido DismutasaRESUMEN
PURPOSE: There is an urgent need for biomarkers and new actionable targets to improve radiosensitivity of triple-negative breast cancer (TNBC) tumors. We characterized the radiosensitizing effects and underlying mechanisms of combined Aurora kinase A (AURKA) and CHK1 inhibition in TNBC. METHODS AND MATERIALS: Different TNBC cell lines were treated with AURKA inhibitor (AURKAi, MLN8237) and CHK1 inhibitor (CHK1i, MK8776). Cell responses to irradiation (IR) were then evaluated. Cell apoptosis, DNA damage, cell cycle distribution, and mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) and Phosphoinositide 3-Kinase (PI3K) pathways were evaluated in vitro. Transcriptomic analysis was performed to facilitate the identification of potential biomarkers. Xenograft and immunohistochemistry were carried out to investigate the radiosensitizing effects of dual inhibition in vivo. Finally, the prognostic effect of CHEK1/AURKA in TNBC samples in the The Cancer Genome Atlas (TCGA) database and our center were analyzed. RESULTS: AURKAi (MLN8237) induced overexpression of phospho-CHK1 in TNBC cells. The addition of MK8776 (CHK1i) to MLN8237 greatly reduced cell viability and increased radiosensitivity compared with either the control or MLN8237 alone in vitro. Mechanistically, dual inhibition resulted in inducing excessive DNA damage by prompting G2/M transition to cells with defective spindles, leading to mitotic catastrophe and induction of apoptosis after IR. We also observed that dual inhibition suppressed the phosphorylation of ERK, while activation of ERK with its agonist or overexpression of active ERK1/2 allele could attenuate the apoptosis induced by dual inhibition with IR. Additionally, dual inhibition of AURKA and CHK1 synergistically enhanced radiosensitivity in MDA-MB-231 xenografts. Moreover, we detected that both CHEK1 and AURKA were overexpressed in patients with TNBC and negatively correlated with patient survival. CONCLUSIONS: Our findings suggested that AURKAi in combination with CHK1i enhanced TNBC radiosensitivity in preclinical models, potentially providing a novel strategy of precision treatment for patients with TNBC.
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Fármacos Sensibilizantes a Radiaciones , Neoplasias de la Mama Triple Negativas , Humanos , Apoptosis , Aurora Quinasa A/metabolismo , Aurora Quinasa A/uso terapéutico , Biomarcadores , Línea Celular Tumoral , Proliferación Celular/efectos de la radiación , Daño del ADN , Fosfatidilinositol 3-Quinasas , Tolerancia a Radiación , Fármacos Sensibilizantes a Radiaciones/uso terapéutico , Neoplasias de la Mama Triple Negativas/tratamiento farmacológico , Neoplasias de la Mama Triple Negativas/radioterapia , Neoplasias de la Mama Triple Negativas/metabolismo , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
Background: Previous studies suggest that physiological feedback can be an effective method for emotion regulation (ER). However, studies on the specific effects of physiological feedback have shown conflicting results due to inconsistencies in study designs. Therefore, we present this systematic review to further validate the effectiveness of physiological feedback for ER, clarify its specific effects, as well as summarize the factors that influence its effectiveness. Method: This systematic review following PRISMA guidelines covers all studies using physiological feedback in emotions. A literature search was conducted in Web of Science, PubMed, PsychINFO, China National Knowledge Infrastructure, and WANFANG DATA. And a standardized quality assessment was performed. Results: We identified 27 relevant articles (25 studies), and the majority of these studies showed a significant regulatory effect of physiological feedback on different emotions. The feedback's content, explanation, authenticity, real-time capability, and modality were the key factors that influenced its effects, and this technology will achieve its optimal ER effect when these factors are considered comprehensively. Conclusions: These findings further confirmed the effectiveness of physiological feedback as an ER method, as well as providing key factors that should be addressed in its application. Meanwhile, due to the limitations of these studies, more well-designed studies are still needed.
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BACKGROUND: We evaluated the safety and immunogenicity of high and low doses of a novel pichia pastoris-expressed bivalent (types 16 and 18) human papillomavirus (HPV) virus-like particle vaccine. METHODS: In this randomized, double-blind, placebo-controlled phase 1 trial, we enrolled 160 healthy females aged 9-45 years in Guangxi, China who were randomized (1:1:2) to receive either low (0.5 mL) or high (1.0 mL) dosages of bivalent HPV vaccine, or placebo (aluminum adjuvant) in a 0, 2, 6 months schedule. Adverse events and other significant conditions that occurred within 30 days after each vaccination were recorded throughout the trial. Sera were collected at days 0, 60, 180 and 210 to measure anti-HPV 16/18 neutralizing antibodies. RESULTS: A total of 160 participants received at least one dose of the HPV vaccine and 152 completed the three dose vaccination series. Reporting rates of adverse events in placebo, low dose (0.5 mL) and high dose (1.0 mL) groups were 47.5 %, 55.0 % and 55.0 %, respectively. No serious adverse events occurred during this trial. 100 % of the participants who received three doses of the HPV vaccine produced neutralizing antibodies against HPV 16/18 vaccine. For HPV 16 and HPV 18, the geometric mean titers (GMTs) were similar between the low dose group (GMTHPV 16 = 10816 [95 % CI: 7824-14953]), GMTHPV 18 = 3966 [95 % CI: 2693-5841]) and high dose group (GMT HPV 16 = 14482 [95 % CI: 10848-19333], GMT HPV 18 = 3428 [95 % CI: 2533-4639]). CONCLUSION: The pichia pastoris-expressed bivalent HPV vaccine was safe and immunogenic in Chinese females aged 9-45 years. The low dosage (0.5 mL) was selected for further immunogenicity and efficacy study.