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Background: Depression has become a multifaceted global health issue, with complex connections to obesity. Weight-adjusted-waist index (WWI) can effectively evaluate central obesity, but the relationship between WWI and depression has not been well studied. The study aims to investigate the potential correlation between these two health parameters. Methods: According to the data from National Health and Nutrition Examination Survey, this cross-sectional study used multiple regression analysis, subgroup analysis, and smooth curve fitting to explore the relationship between WWI and depression. The assessment ability of WWI was evaluated and compared to other obesity indicators using the receiver operating characteristic (ROC) curve. Results: This study analyzed 38,154 participants. Higher WWI is associated with higher depression scores (ß = 0.41; 95% CI, 0.36-0.47). After adjusting for various confounding factors, the positive correlation between WWI and depression remained significant (P for trend < 0.0001). Nonlinear positive correlation was detected with a breakpoint of 11.14. ROC analysis shows that compared to other obesity indicators (ROCWWI = 0.593; ROCBMI = 0.584; and ROCWC = 0.581), the correlation between WWI and depression has better discrimination and accuracy. DII mediated 4.93%, SII mediated 5.08%, and sedentary mediated 0.35% of the total association between WWI and depression. Conclusion: WWI levels were related to an increased likelihood of depression and showed a stronger relationship than BMI and waist circumference. Our findings indicated that WWI may serve as a simple anthropometric index to evaluate depression.
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In this study, a novel quality control strategy was proposed, aiming to establish a multivariate specification for the processing step by exploring the correlation between colors, chemical components, and hemostatic effects of the carbonized Typhae pollen (CTP) using multivariate statistical analysis. The CTP samples were stir-fried at different durations. Afterward, the colorimeter and LC-MS techniques were applied to characterize the CTP samples, followed by the determination of bleeding time and clotting time using mice to evaluate their hemostatic effect. Then, principal component analysis, hierarchical cluster analysis, and multi-block partial least squares were used for data analysis on colors, chemical components, and their correlation with the hemostatic effect. Consequently, 13 critical quality attributes (CQAs) of CTP were identified via multivariate statistical analysis-L*, a*, b*, 3,4-dihydroxybenzoic acid, 4-hydroxybenzoic acid, 3-hydroxybenzoic acid, quercetin-3-O-glucoside, azelaic acid, kaempferol-3-O-glucoside, quercetin, naringenin, kaempferol, and isorhamnetin. The multivariate specification method involving the 13 CQAs was developed and visualized in the latent variable space of the partial least squares model, indicating that the proposed method was successfully applied to assess the quality of CTP and the degree of carbonization. Most importantly, this study offers a novel insight into the control of processing for carbonized Chinese herbal medicines.
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Polen , Control de Calidad , Typhaceae , Animales , Polen/química , Análisis Multivariante , Ratones , Typhaceae/química , Espectrometría de Masas/métodos , Cromatografía Liquida/métodos , Masculino , Medicamentos Herbarios Chinos/química , Medicamentos Herbarios Chinos/análisis , Cromatografía Líquida con Espectrometría de MasasRESUMEN
Objective@#To develop the Family-School-Community Cooperation Dilemma Scale for Nutritional Education in Primary Schools Students, and to determine its reliability and validity, in order to provide a basis for developing targeted strategies to promote family-school-community cooperation in the area of nutritional education.@*Methods@#Based on overlapping spheres of influence theory, the initial scale was developed through a qualitative and literature review, discussion with Delphi experts and a pilot survey from July 2022 to July 2023. From July to September 2023, a total of 125 primary school parents, 118 primary school teachers and 113 community personnel were selected from six cities in Jiangsu Province by convenient sampling methods, who were investigated to test the reliability and validity of the scale and to develop a formal scale.@*Results@#The final Family-School-Community Cooperation Dilemma Scale for Nutritional Education in Primary School students consisted of 3 dimensions and 19 items. The exploratory analysis extracted three metric factors, with a contribution ratio of 69.07% to the accumulated variance. The mean scale component effectiveness was 0.94, and the coefficient of association between the respective dimensions and the scale ranged from 0.80 to 0.91.The overall Cronbach α coefficient for the scale was 0.95, the folded half reliability was 0.87, and the retest reliability was 0.98.@*Conclusion@#The Family-School-Community Cooperation Dilemma Scale for Nutritional Education in Primary School Students has good reliability and validity, and can be used to measure the degree of the family-school-community cooperation dilemma regarding nutritional education in primary school students.
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@#Objective To investigate the diagnostic value and clinical significance of hypersensitive C-reactive protein(hs-CRP),procalcitonin(PCT)combined with interleukin-6(IL-6)in children with severe hand-foot-mouth disease.Methods A total of 62 children hospitalized in our hospital from January 2022 to December 2022 were collected as research objects.According to the severity of infection,they were divided into observation group(severe infection group)with 29 cases and control group(mild infection group)with 33 cases.The differences of general data,total leukocyte count,neutrophil count,lymphocyte count,platelet count,hs-CRP,PCT,IL-6 and creatine kinase isoenzyme(CK-MB)between the two groups and their clinical applications were analyzed and compared.Results The total white blood cell count,neutrophil count,lymphocyte count,hs-CRP,PCT and IL-6 in the observation group were higher than those in the control group,and the difference has statistically significant.Receiver operator characteristic(ROC)curve analysis of hs-CRP predicted the sensitivity and specificity of severe infection of hand-foot-mouth disease were 79.3%and 93.9%(95%CI:0.852-10.985,P<0.05);The sensitivity and specificity of PCT were 93.1%and 84.8%(95%CI:0.907-1,P<0.05);The sensitivity and specificity of IL-6 were 96.6%and 87.9%(95%CI:0.945-1,P<0.05).Conclusions In hand-foot-mouth classification,PCT and IL-6 are highly sensitive.Although hs-CRP is less sensitive than the former,its specificity is higher than the former.Therefore,the combination of hs-CRP,PCT and IL-6 has higher value for hand-foot-mouth classification.
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Objective To describe the incidence and mortality of brain tumors in China in 2020 and to predict the disease burden up to 2040.Methods The brain tumor incidence and mortality in 2020 were recorded based on the data from International Agency for Cancer Research(IARC),Cancer Today database.The incidence and mortality were standardized by age using Segi's world standard population.The burden of brain tumors in 2040 was predicted with assuming that national rates remained constant in 2020.Results It was estimated there were approximately 79 600 new brain tumors cases and 65 200 deaths in China in 2020.The age-standardized incidence and mortality rates of brain tumors in China were 4.1/100 000 and 3.2/100 000,respectively,which were lower than the United States of America,most of European countries and Australia.The incidence and mortality were higher than Africa,central America,and the Caribbean.From 2020 to 2040,the brain tumors cases and deaths are predicted to have an increase as 32.1%and 41.5%respectively.Conclusions The disease burden of brain tumors was still heavy in China.Further studies are urgently needed to clarify the epidemic trend of tissue typing and risk factors of brain tumors,which may support the development of effective prevention strategies.
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Objective To reduce the amount of public hospital arrears,strengthen debt management,improve the over-all operational efficiency of the hospital,promote fine management of the hospital,and boost high-quality development of the hos-pital.Methods We analyzed relevant data collected from 3 000 inpatients,including 486 with outstanding debts,treated at a tertiary public hospital in Chongqing between 2019 and 2023.Single factor analysis and binary logistic regression analysis were performed to identify the causes of medical arrears,and subsequently propose effective debt management strategies.Results Uni-variate analysis revealed that factors such as medical insurance status,department,gender,age,and cause of arrears significantly influenced the occurrence of medical arrears(P<0.05).The analysis based on the binary logistic model exhibited a good fit with the observed values,with the value of each classification factor's significance less than 0.05.The incidence of arrears was higher among self-funded patients compared to those with medical insurance.The surgical department had the highest rate of arrears,ne-cessitating specialized training for better debt management.The patients aged between 41 and 60 had the highest arrear rate,indi-cating the need for professionally trained nurses to pay close attention to this age group.The primary reasons for arrears included deliberate evasion,disputes,questionable sources(green passage),unforeseen public events,and economic difficulties.Conclusion To effectively manage medical arrears,hospitals should enhance their debt management systems,delineate depart-mental responsibilities and management processes,and implement stringent controls at key points from admission to discharge.
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Multisystem inflammatory syndrome in children is a disease related with severe acute respiratory syndrome corona-virus 2 infection,which can involve multiple system damage.Most cases included features of shock,cardiac dysfunction,gastrointestinal symptoms,significantly elevated markers of inflammation and cardiac damage,and positive test results for SARS-CoV-2 by serology.Although its clinical features overlap with Kawasaki disease,it is more likely to occur in older children and adolescents,and most of them need to be treated with intensive care and a variety of immunomodulators.At present,the pathogenesis and long-term prognosis of the disease need to be further studied.
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The 59th European Association for the Study of Diabetes(EASD) annual meeting was held in Hamburg, Germany from October 2nd to 6th, 2023. In the past decades, there have been significant advancements in the clinical management of diabetes. Novel anti-hyperglycemic medications, particularly those targeting the glucagon-like peptide-1 receptor and dual/multiple receptors, have garnered attention. These medications show great promise in glycemic control, weight reduction, metabolic improvements, and additional benefits. This article provided an overview of some of the key topics discussed at this EASD conference.
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We retrospectively analyzed therapy efficacy and the adverse reactions of 10 patients suffering from systemic lupus erythematosus (SLE) with intestinal involvement treated with rituximab (RTX). Patients were hospitalized in the Department of Rheumatology and Immunology of the First Medical Center of PLA General Hospital from January 2015 to January 2023. Among the 10 patients, two were men and eight were women. The age of the cohort was (41.9±8.8) years. The age at disease onset was (28.8±9.2) years. The total course of the SLE diagnosis was(109.6±59.9) months. The course of the diagnosis of SLE with intestinal involvement was (89.3±50.2) months. The time from the appearance of intestinal symptoms to the diagnosis of SLE with intestinal involvement was 1.5 (1.0,8.0) months. The time from the diagnosis of SLE with intestinal involvement to RTX use was 13.0 (1.0,46.3) months. Follow-up duration after application of RTX treatment was (55.3±28.4) months. There were five cases of abdominal pain, four cases of abdominal distension, nine cases of diarrhea, three cases of nervous-system involvement, nine cases of lupus nephritis, and seven cases of serositis. All 10 patients underwent computed tomography and radiology of the abdomen. Eight patients had intestinal-wall edema, seven suffered intestinal dilation, four had target signs, three suffered congestion of mesenteric blood vessels, eight had increased mesenteric-fat density, and six had false intestinal obstruction. All 10 patients showed a low level of complement C3 (250-750 mg/L). Nine cases showed a low level of complement C4 (10-90 mg/L). The SLE disease activity index 2000 (SLEDAI-2K) at baseline in 10 patients was 20.5 (17.8, 30.0). After receiving RTX (0.5 g: day 1, day 14, or 375 mg/m 2: day 1, day 14) induction treatment, the intestinal symptoms of 10 cases were relieved completely. Four patients had adverse reactions, of which three received a high-dose glucocorticoid combined with RTX treatment simultaneously. Adverse reactions manifested mainly as a reduced level of IgG and infection with herpes simplex virus in one case, reduced level of IgG and lung infection in one patient, lung infection in one case, and reduced IgG level in one patient. RTX may an efficacious treatment strategy for patients suffering from refractory SLE with intestinal involvement.
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@#The treatment of patients with advanced lung cancer has been revolutionized with the advent of immunotherapy. However, not all patients can benefit equally from immunotherapy. In recent years, the relationship between intestinal flora and the efficacy of immunotherapy has gradually attracted scholars' attention. During the treatment of immune checkpoint inhibitors, the use of antibiotics, proton pump inhibitors and other drugs will affect the patient's intestinal flora, thus affecting the efficacy of immune checkpoint inhibitors, leading to poor prognosis of patients. This review will discuss that antibiotics and proton pump inhibitors reduce the efficacy of immunotherapy by affecting the diversity of intestinal flora, in order to facilitate the rational use of related drugs in clinical practice and improve the patient's outcomes.
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@#Objective To analyze the current development of researches on biomarkers for predicting the efficacy of immunotherapy in non-small cell lung cancer and to provide reference for subsequent studies. Methods Studies on biomarkers for predicting the efficacy of immunotherapy for non-small cell lung cancer indexed in the Web of Science Core Collection from 2017 to 2021 were searched by computer. The annual distribution, journals, authors, countries, institutions, and keywords of studies were visualized and analyzed by CiteSpace. Results A total of 426 studies were collected, including 298 articles and 128 reviews. The average number of published studies was about 85, and increased year by year. PD-L1 expression, tumor mutational burden, tumor microenvironment and liquid biopsy were hot keywords in this field. Conclusion In the future, combination of biomarkers in the liquid biopsy and tumor microenvironment with radiomics analysis will be the research hotspot and frontier in this field for more accurate assessment with tumor-related signatures such as lymphocytic immune status and characteristics of tumor lesions in non-small cell lung cancer patients.
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OBJECTIVE@#To investigate the associated factors of endogenous erythropoietin (EPO) and its association with 10-year risks of atherosclerotic cardiovascular disease in a Chinese community-based general population.@*METHODS@#The participants of this study were from an atherosclerosis cohort survey which was established by the Department of Cardiology, Peking University First Hospital in 2011. The cohort survey was performed in the Gucheng and Pingguoyuan communities of Shijingshan district in Beijing, China. The inclusion criteria of this study were: (1) endogenous EPO was measured; (2) health questionnaire data and other clinical data were complete; (3) participatants who had cardiovascular or cerebrovascular diseases (defined as self-reported coronary heart disease, stroke or transient ischemic attack) or anemia or estimated glomerular filtration rate (eGFR) < 60 mL/(min·1.73 m2) at baseline were excluded. Multivariate linear regression model was used to examine the associated factors of endogenous EPO. The participants were grouped into low (< 5%), moderate (5%-10%) and high risk (≥10%) groups, based on predicted 10-year cardiovascular disease risk using the prediction for atherosclerotic cardiovascular disease risk in China (China-PAR) equations.@*RESULTS@#A total of 4 013 participants were included. Mean age of them was (55.9±8.2) years, 62.2% (n=2 496) of them were female, and 46.3% (n=1 859), 70.9% (n=2 845), 21.9% (n=879) had hypertension, dyslipidemia and diabetes, individually. The average body mass index was (26.1±3.3) kg/m2. The median of EPO level was 12.8 (9.3-17.4) IU/L and 25.1% (n=998) were at high 10-years risk of cardiovascular disease. Hemoglobin (β=-0.05, 95%CI: -0.07 to -0.04) and eGFR ≥90 mL/(min·1.73 m2) (β=-0.05, 95%CI: -0.07 to -0.04) were associated with lower in transformed EPO levels while hypertension (β=0.08, 95%CI: 0.05 to 0.12) and obesity (β=0.14, 95%CI: 0.09 to 0.18) were associated with higher in transformed EPO levels in multivariate linear regression analyses. Ten-year cardiovascular disease risks were positively associated with in transformed EPO levels (β=0.07, 95%CI: 0.05 to 0.09). The participants at moderate and high cardiovascular disease risks had significant higher EPO levels than the low risk group (all P < 0.05).@*CONCLUSION@#In community-based Beijing populations, endogenous EPO was associated with hemoglobin, renal function, obesity and hypertension. Individuals at high 10-years cardiovascular disease risks have higher endogenous EPO levels. Endogenous EPO may be a potential risk marker of cardiovascular disease.
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Femenino , Humanos , Masculino , Persona de Mediana Edad , Enfermedades Cardiovasculares/epidemiología , Eritropoyetina , Hemoglobinas , Hipertensión/epidemiología , Obesidad , Factores de RiesgoRESUMEN
Visually induced motion sickness(VIMS)is the major barrier to be broken in the development of virtual reality(VR)technology,which seriously affects the progress in the VR industry.Therefore,the detection and evaluation of VIMS has become a hot research topic nowadays.We review the progress in physiological assessment of VIMS in VR based on several physiological indicators,including electroencephalogram(EEG),postural sway,eye movements,heart rate variability,and skin electrical signals,and summarize the available therapies,aiming to provide an outlook on the future research directions of VIMS.
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Humanos , Mareo por Movimiento/diagnóstico , Realidad Virtual , Frecuencia CardíacaRESUMEN
OBJECTIVE@#To describe the submucosal microbial profiles of peri-implantitis and healthy implants, and to explore bacteria that might be correlated with clinical parameters.@*METHODS@#In the present cross-sectional study, 49 patients were recruited. Each patient contributed with one implant, submucosal biofilms were collected from 20 healthy implants and 29 implants with peri-implantitis. DNA was extracted and bacterial 16S ribosomal RNA (16S rRNA) genes were amplified. Submucosal biofilms were analyzed using 16S rRNA sequencing at Illumina MiSeq platform. Differences between the groups were determined by analyzing α diversity, microbial component and microbial structure. The potential correlation between the bacteria with pocket probing depth (PPD) of peri-implant calculated by Spearman correlation analysis.@*RESULTS@#The α diversity of submucosal microbial of health group was significantly lower than that in peri-implantitis group (Chao1 index: 236.85±66.13 vs. 150.54±57.43, P < 0.001; Shannon index: 3.42±0.48 vs. 3.02±0.65, P=0.032). Principal coordinated analysis showed that the submucosal microbial structure had significant difference between healthy and peri-implantitis groups [R2=0.243, P=0.001, analysis of similarities (ANOSIM)]. Compared with healthy implants, relative abundance of periodontal pathogens were higher in peri-implantitis, including members of the red complex (Porphyromonas gingivalis, Tannerella forsythia, Treponema denticola) and some members of orange complex (Precotella intermedia, Eubacterium nodatum, Parvimonas micra), as well as some new periodontal pathogens, such as Fillifactor alocis, Fretibacterium fastidiosum, Desulfobulbus sp._HMT_041, and Porphyromonas endodontalis. Spearman correlation analysis revealed that the relative abundance of Treponema denticola (r=0.686, P < 0.001), Tannerella forsythia (r=0.675, P < 0.001), Fretibacterium sp. (r=0.671, P < 0.001), Desulfobulbus sp._HMT_041 (r=0.664, P < 0.001), Filifactor alocis (r=0.642, P < 0.001), Fretibacterium fastidiosum (r=0.604, P < 0.001), Porphyromonas gingivalis (r=0.597, P < 0.001), Porphyromonas endodontalis (r=0.573, P < 0.001) were positive correlated with PPD. While the relative abundance of Rothia aeria (r=-0.615, P < 0.001) showed negatively correlation with PPD.@*CONCLUSION@#Marked differences were observed in the microbial profiles of healthy implants and peri-implantitis. The members of red and orange complex as well as some new periodontal pathogens seem to play an important role in peri-implant disease. Compared with healthy implants, the submucosal microbial of peri-implantitis were characterized by high species richness and diversity.
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Humanos , Periimplantitis/microbiología , Estudios Transversales , ARN Ribosómico 16S/genética , Carga Bacteriana , Porphyromonas gingivalis , Implantes DentalesRESUMEN
OBJECTIVE@#To explore the brain effect mechanism and the correlation between brain functional imaging and cognitive function in treatment of depressive disorder (DD) with transcutaneous auricular vagus nerve stimulation (taVNS) based on the resting-state functional magenetic reasonance imaging (rs-fMRI).@*METHODS@#Thirty-two DD patients were included in a depression group and 32 subjects of healthy condition were enrolled in a normal group. In the depression group, the taVNS was applied to bilateral Xin (CO15) and Shen (CO10), at disperse-dense wave, 4 Hz/20 Hz in frequency and current intensity ≤20 mA depending on patient's tolerance, 30 min each time, twice daily. The duration of treatment consisted of 8 weeks. The patients of two groups were undertaken rs-fMRI scanning. The scores of Hamilton depression scale (HAMD), Hamilton anxiety scale (HAMA) and Wisconsin card sorting test (WCST) were observed in the normal group at baseline and the depression group before and after treatment separately. The differential brain regions were observed before and after treatment in the two groups and the value of degree centrality (DC) of fMRI was obtained. Their correlation was analyzed in terms of HAMD, HAMA and WCST scores.@*RESULTS@#The scores of HAMD and HAMA in the depression group were all higher than those in the normal group (P<0.05). After treatment, the scores of HAMD and HAMA were lower than those before treatment in the depression group; the scores of total responses, response errors and perseverative errors of WCST were all lower than those before treatment (P<0.05). The brain regions with significant differences included the left inferior temporal gyrus, the left cerebellar peduncles region 1, the left insula, the right putamen, the bilateral supplementary motor area and the right middle frontal gyrus. After treatment, the value of DC in left supplementary motor area was negatively correlated to HAMD and HAMA scores respectively (r=-0.324, P=0.012; r=-0.310, P=0.015); the value of DC in left cerebellar peduncles region 1 was negatively correlated to the total responses of WCST (r=-0.322, P=0.013), and the left insula was positively correlated to the total responses of WCST (r=0.271, P=0.036).@*CONCLUSION@#The taVNS can modulate the intensity of the functional activities of some brain regions so as to relieve depressive symptoms and improve cognitive function.
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Humanos , Depresión/terapia , Imagen por Resonancia Magnética/métodos , Estimulación del Nervio Vago/métodos , Encéfalo/diagnóstico por imagen , Estimulación Eléctrica Transcutánea del Nervio/métodos , Nervio VagoRESUMEN
Objective:To evaluate the effectiveness and safety of concurrent chemoradiotherapy combined with nimotuzumab in the treatment of patients with inoperable esophageal squamous cell carcinoma (ESCC).Methods:A retrospective analysis was conducted on the clinical data of 503 patients with inoperable ESCC who underwent concurrent chemoradiotherapy in the Department of Radiation Oncology, Changzhou No. 2 People′s Hospital Affiliated to Nanjing Medical University and Department of Radiation Oncology, Affiliated Hospital of Jiangnan University from 2014 to 2020. Among these patients, 69 received concurrent chemoradiotherapy combined with nimotuzumab (the combined therapy group) and 434 received concurrent chemoradiotherapy alone (the concurrent chemoradiotherapy group). Patients of both groups were matched at a ratio of 1∶2 using the propensity score matching (PSM) method. As a result, 168 patients were determined for clinical analysis, including 61 in the combined therapy group and 107 in the concurrent chemoradiotherapy group. The short-term efficacy and adverse reactions of both groups were compared. The overall survival (OS) curves and progression-free survival (PFS) curves were plotted using the Kaplan-Meier method for the Log-rank test.Results:The two groups showed no statistical difference ( P > 0.05) in clinical baseline characteristics after the PSM. The objective response rate (ORR) of the combined therapy group was significantly higher than that of the concurrent chemoradiotherapy group with statistically significant differences (85.2% vs. 71.0%, χ2 = 4.33, P = 0.037). There was no statistical difference (98.4% vs. 91.6%, P > 0.05) in the disease control rate (DCR) between the two groups. The combined therapy group had median PFS of 28.07 months and 1-, 3-, and 5-year PFS ratios of 78.2%, 37.5% and 29.1%, respectively. The concurrent chemoradiotherapy group had mPFS of 19.54 months and 1-, 3-, and 5-year PFS ratios of 72.9%, 28.3% and 21.3%, respectively. Both groups showed statistically significant differences in PFS ( χ2 = 4.49, P = 0.034). The combined group had median OS of 34.93 months and 1-, 3-, and 5-year OS ratios of 88.5%, 46.8% and 37.4%, respectively. The concurrent chemoradiotherapy group had mOS of 24.30 months and 1-, 3-, and 5-year OS ratios of 81.3%, 35.2% and 28.0%, respectively. Both groups showed statistically significant differences in OS (χ 2= 5.11, P = 0.024), but did not show statistical differences ( P > 0.05) in the severity degree of each adverse effect during the treatment. Conclusions:Concurrent chemoradiotherapy combined with nimotuzumab can improve the ORR and prolong the PFS and OS of patients with inoperable ESCC compared with concurrent chemoradiotherapy alone. Furthermore, combining with nimotuzumab does not increase adverse effects and can be tolerated by patients with high safety.
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Objective:To evaluate the effect of niraparib, the poly (ADP-ribose) polymerase (PARP) inhibitor, on the radiosensitivity of esophageal squamous cell carcinoma (ESCC) and to preliminarily investigate its mechanism.Methods:Human esophageal squamous cell carcinoma cells ECA-109 and KYSE-150 were divided into the control, niraparib, single irradiation, combined (niraparib+irradiation) groups. Cell proliferation was measured by CCK-8 assay. The changes of cell survival rate were detected by colony formation assay. The changes of cell cycle and apoptosis were analyzed by flow cytometry. The number of γH2AX foci was detected by immunofluorescence, and the expression levels of PARP-1, cleaved-PARP, RAD51, mitogen-activated protein kinase (MAPK) [extracellular signal-regulated kinase 1 and 2 (ERK1/2) ] and p-MAPK (ERK1/2) proteins were determined by Western blot. All data were expressed as Mean±SD. Data between two groups conforming to normal distribution through the normality test were subject to independent sample t-test and multiple groups were analyzed using one-way ANOVA. Results:In human ESCC cells ECA-109 and KYSE-150, the proliferation of ESCC cells was significantly inhibited by niraparib combined with irradiation, and the values of average lethal dose (D 0), quasi-threshould dose(D q), survival fraction after 2 Gy irradiation (SF 2) in the combined group were decreased compared with those in the single irradiation group. The effect of irradiation alone on apoptosis of ECA-109 and KYSE-150 cells was limited. Compared to single irradiation group, irradiation combined with niraparib further increased the apoptosis rate in ESCC cells ( P=0.015, P=0.006). In ECA-109 cells, G 2/M phase arrest was significantly increased in combined group compared with irradiation alone group ( P<0.001). In ECA-109 cells, the number of γH2AX foci in combined group was higher than that in the single irradiation group after 2 h, and showed a significantly slower decay of γH2AX foci ( P<0.001). Moreover, niraparib combined with irradiation enhanced the radiation-induced cleavage of PARP-1 and down-regulated the expression of Rad51 and p-MAPK(ERK1/2). Conclusion:Niraparib can increase the radiosensitivity of esophageal cancer cells by inhibiting cell proliferation, promoting cell apoptosis, inhibiting the repair of DNA damage and regulating the MARK-ERK signaling pathway.
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Objective:To study the effects of poly adenosine diphosphate ribose polymerase (PARP) inhibitors niraparib and pamiparib on the radiosensitivity of breast cancer cell lines MCF-7 and MDA-MB-436, and to explore its mechanism.Methods:MCF-7 and MDA-MB-436 cells were divided into control group, niraparib group, pamiparib group, radiation group, combination group treated with niraparib and radiation, and combination group treated with pamiparib and radiation, respectively. The effects of drugs on cell proliferation and radiosensitivity were measured by CCK-8 assay and colony formation assay, respectively. The effect of drugs combined with radiation on cell cycle and apoptosis were detected by flow cytometry. Immunofluorescence method was used to detect the changes of γ-H2AX focal number of cells. The expressions of FANCG, Bax and Bcl-2 mRNA and protein were detected by qPCR and Western blot, respectively.Results:Both niraparib and pamiparib inhibited the proliferation of breast cancer cells MCF-7 and MDA-MB-436 in a time-dose dependent manner. With the increase of irradiation dose, D0, Dq, SF2 value of MCF-7 and MDA-MB-436 cells decreased, and SER D0 and SER Dq value increased. Compared with control group, the percentages of cells in G 2/M phase were increased ( tMCF-7=41.66, 44.08, P<0.05; t436=24.69, 18.91, P<0.05), the percentage of cells in G 0/G 1 phase were decreased ( tMCF-7=8.67, 29.61, P<0.05; t436=26.39, 29.12, P<0.05), and the cell apoptosis rate was significantly increased ( tMCF-7=11.17, 11.71, P<0.05; t436=42.68, 15.89, P<0.05) in the combination group. Compared with control group, the number of γ-H2AX foci of MCF-7 cells in the radiation group and combination group treated with niraparib and radiation increased significantly at 2 h after irradiation ( t=8.89, 21.72, P<0.05). At 24 h after irradiation, the number of γ-H2AX foci basically returned to normal level in the radiation group but remained at a higher level in the combination group ( t=8.82, P<0.05). Compared with control group, the expressions of FANCG and Bcl-2 mRNA decreased ( tFANCG=14.07, P<0.05; tBcl-2=29.21, P<0.05), the expression of Bax mRNA increased ( t=8.90, P<0.05), and the expression of FANCG and Bcl-2 proteins decreased ( tFANCG=7.09, P<0.05; tBcl-2=10.24, P<0.05), while the expression of Bax protein increased ( t=2.90, P<0.05) in the combination group. Conclusions:PARP inhibitors niraparib and pamiparib can increase the radiosensitivity of breast cancer MCF-7 and MDA-MB-436 cells probably through down-regulating the expression of FANCG in FA-BRCA pathway, up-regulating apoptosis-related genes and inhibiting DNA damage repair.
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This study was aimed at identifying the bioactive components of the crude and stir-baked hawthorn for invigorating spleen and promoting digestion, respectively, to clarify the processing mechanism of hawthorn by applying the partial least squares(PLS) algorithm to build the spectrum-effect relationship model. Firstly, different polar fractions of crude and stir-baked hawthorn aqueous extracts and combinations of different fractions were prepared, respectively. Then, the contents of 24 chemical components were determined by ultra-high performance liquid chromatography-mass spectrometry. The effects of different polar fractions of crude hawthorn and stir-baked hawthorn aqueous extracts and combinations of different fractions were evaluated by measuring the gastric emptying rate and small intestinal propulsion rate. Finally, the PLS algorithm was used to establish the spectrum-effect relationship model. The results showed that there were significant differences in the contents of 24 chemical components for different polar fractions of crude and stir-baked hawthorn aqueous extracts and combinations of different fractions, and the gastric emptying rate and small intestinal propulsion rate of model rats were improved by administration of different polar fractions of crude and stir-baked hawthorn aqueous extracts and combinations of different fractions. The bioactive components of crude hawthorn identified by PLS models were vitexin-4″-O-glucoside, vitexin-2″-O-rhamnoside, neochlorogenic acid, rutin, gallic acid, vanillic acid, citric acid, malic acid, quinic acid and fumaric acid, while neochlorogenic acid, cryptochlorogenic acid, rutin, gallic acid, vanillic acid, citric acid, quinic acid and fumaric acid were the bioactive components of stir-baked hawthorn. This study provided data support and scientific basis for identifying the bioactive components of crude and stir-baked hawthorn, and clarifying the processing mechanism of hawthorn.
Asunto(s)
Animales , Ratas , Bazo , Crataegus , Ácido Quínico , Análisis de los Mínimos Cuadrados , Ácido Vanílico , Algoritmos , DigestiónRESUMEN
Although acute promyelocytic leukaemia (APL) is a highly curable disease, challenges of early death (ED) and relapse still exist, and real-world data are scarce in the ATRA plus ATO era. A total of 1105 APL patients from 1990 to 2020 were enrolled and categorized into three treatment periods, namely ATRA, ATRA plus ATO, and risk-adapted therapy. The early death (ED) rate was 20.2%, 10.1%, and 7.0%, respectively, in three periods, while there was no significant decline in the 7-day death rate. Consistently, the overall survival (OS) and disease-free survival (DFS) of APL patients markedly improved over time. Despite the last two periods exhibiting similar DFS, the chemotherapy load was substantially lower in Period 3. Notably, leveraging older age and higher WBC count (especially > 50 × 109/L), we could identify a small group of extremely high-risk patients who had a very high ED rate and poor prognosis, while those with NRAS mutations and higher WBC tended to relapse, both representing obstacles to curing all patients. In conclusion, the evolvement of treatment paradigms can reduce the ED rate, improve clinical outcomes, and spare patients the toxicity of chemotherapy. Special care and innovative agents are warranted for the particularly high-risk APL.