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The extension of the cosmic-ray spectrum beyond 1 petaelectronvolt (PeV; 1015 electronvolts) indicates the existence of the so-called PeVatrons-cosmic-ray factories that accelerate particles to PeV energies. We need to locate and identify such objects to find the origin of Galactic cosmic rays1. The principal signature of both electron and proton PeVatrons is ultrahigh-energy (exceeding 100 TeV) γ radiation. Evidence of the presence of a proton PeVatron has been found in the Galactic Centre, according to the detection of a hard-spectrum radiation extending to 0.04 PeV (ref. 2). Although γ-rays with energies slightly higher than 0.1 PeV have been reported from a few objects in the Galactic plane3-6, unbiased identification and in-depth exploration of PeVatrons requires detection of γ-rays with energies well above 0.1 PeV. Here we report the detection of more than 530 photons at energies above 100 teraelectronvolts and up to 1.4 PeV from 12 ultrahigh-energy γ-ray sources with a statistical significance greater than seven standard deviations. Despite having several potential counterparts in their proximity, including pulsar wind nebulae, supernova remnants and star-forming regions, the PeVatrons responsible for the ultrahigh-energy γ-rays have not yet been firmly localized and identified (except for the Crab Nebula), leaving open the origin of these extreme accelerators.
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Both short (≤6 h per night) and long sleep duration (≥9 h per night) are associated with increased risk of chronic diseases. Despite evidence linking habitual sleep duration and risk of disease, the genetic determinants of sleep duration in the general population are poorly understood, especially outside of European (EUR) populations. Here, we report that a polygenic score of 78 European ancestry sleep duration single-nucleotide polymorphisms (SNPs) is associated with sleep duration in an African (n = 7288; P = 0.003), an East Asian (n = 13 618; P = 6 × 10-4) and a South Asian (n = 7485; P = 0.025) genetic ancestry cohort, but not in a Hispanic/Latino cohort (n = 8726; P = 0.71). Furthermore, in a pan-ancestry (N = 483 235) meta-analysis of genome-wide association studies (GWAS) for habitual sleep duration, 73 loci are associated with genome-wide statistical significance. Follow-up of five loci (near HACD2, COG5, PRR12, SH3RF1 and KCNQ5) identified expression-quantitative trait loci for PRR12 and COG5 in brain tissues and pleiotropic associations with cardiovascular and neuropsychiatric traits. Overall, our results suggest that the genetic basis of sleep duration is at least partially shared across diverse ancestry groups.
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Estudio de Asociación del Genoma Completo , Duración del Sueño , Humanos , Estudio de Asociación del Genoma Completo/métodos , Autoinforme , Sitios de Carácter Cuantitativo , Sueño/genética , Polimorfismo de Nucleótido Simple , Predisposición Genética a la Enfermedad , Sitios GenéticosRESUMEN
In this Letter we try to search for signals generated by ultraheavy dark matter at the Large High Altitude Air Shower Observatory (LHAASO) data. We look for possible γ rays by dark matter annihilation or decay from 16 dwarf spheroidal galaxies in the field of view of the LHAASO. Dwarf spheroidal galaxies are among the most promising targets for indirect detection of dark matter that have low fluxes of astrophysical γ-ray background while having large amount of dark matter. By analyzing more than 700 days of observational data at LHAASO, no significant dark matter signal from 1 TeV to 1 EeV is detected. Accordingly we derive the most stringent constraints on the ultraheavy dark matter annihilation cross section up to EeV. The constraints on the lifetime of dark matter in decay mode are also derived.
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Epitaxial growth is a versatile method to prepare two-dimensional van der Waals ferroelectrics like group IV monochalcogenides which have potential for novel electronic devices and sensors. We systematically study SnSe monolayer islands grown by molecular beam epitaxy, especially the effect of annealing temperature on shape and morphology of the edges. Characterization of the samples by scanning tunneling microscopy reveals that the shape of the islands changes from fractal-dendritic after deposition at room temperature to a compact rhombic shape through annealing, but ripening processes are absent up to the desorption temperature. A two-step growth process leads to large, epitaxially aligned rhombic islands bounded by well-defined110-edges (armchair-like), which we claim to be the equilibrium shape of the stoichiometric SnSe monolayer islands. The relaxation of the energetically favorable edges is detected in atomically resolved STM images. The experimental findings are supported by the results of our first-principles calculations, which provide insights into the energetics of the edges, their reconstructions, and yields the equilibrium shapes of the islands which are in good agreement with the experiment.
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AIM: To develop and validate a progressive prediction model for estimating the time to progression (TTP) of sub-solid pulmonary nodules (SSNs). MATERIALS AND METHODS: A total of 126 cases who met inclusion and exclusion criteria were included in the study. The primary endpoint of the study was TTP of SSNs. Baseline characteristics were assessed in terms of clinical and CT semantic features. Kaplan-Meier analysis and Cox regression analysis were performed to determine the relationship between SSNs TTP and factors from the entire data set. The nomogram was constructed based on the result of multivariate analysis and internal validation was performed using the bootstrapping. The nomogram's performance was assessed with the C-index, calibration curves, and decision curve analysis. RESULTS: The median follow-up time of the population was 42.5 (21.5) months. On Kaplan-Meier analysis, patients with higher or positive values of the indices had higher cumulative progression rates (p<0.05). Multivariate Cox regression models identified diameter, consolidation tumour ratio (CTR), morphology, and vasodilation sign (VDS) as independent risk factors of TTP. These predictors were included in the final model to estimate individual probabilities of progression in the 3 years, which performed well in the discrimination (the C-index was 0.901 [95%CI: 0.830-0.981] and 0.875 [95%CI: 0.805-0.942] in the training and internally validation sets). CONCLUSION: The radiological semantic features nomogram is a promising and favourable prognostic biomarker for predicting progression and may aid in clinical risk stratification and decision-making for SSNs.
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Nomogramas , Semántica , Humanos , Estudios de Seguimiento , Calibración , Estimación de Kaplan-Meier , Tomografía Computarizada por Rayos XRESUMEN
OBJECTIVES: An increasing trend of pancreatic cancer in young adults has emerged in some countries. This study aimed to investigate global trends of pancreatic cancer in young adults and explore the impact of exposure to risk factors on pancreatic cancer incidence during youth. METHODS: Global and national data on pancreatic cancer incidence, disability-adjusted life-years, attributive mortality, and summary exposure values of risk factors were retrieved from the Global Burden of Disease 2019. The average annual percent change (AAPC) of incidence and mortality was calculated. Additionally, generalized additive models were applied to explore the non-linear associations between the levels and changes in the Human Development Index and AAPC. RESULTS: Global pancreatic cancer incidence increased during various periods from 1990 to 2019, particularly in adults aged <45 years from 2010 to 2019, at an average annual increase rate of 0.7% (95% confidence interval: 0.4-1.0%). The AAPC of early-onset pancreatic cancer incidence from 2010 to 2019 was negatively correlated with Human Development Index levels in both 2010 and 2019 but positively correlated with Human Development Index acceleration. Significant increases in early-onset pancreatic cancer incidence were observed over this period in 32 of 88 countries, primarily in South America, North America, Oceania, and Africa. Early-onset pancreatic cancer mortality attributed to high body mass index and fasting plasma glucose increased, while that attributed to tobacco use declined. CONCLUSIONS: An increasing trend has emerged in the global incidence and burden of early-onset pancreatic cancer over the last few decades. This rise may partly be attributed to global epidemics of high body mass index and fasting plasma glucose.
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Glucemia , Neoplasias Pancreáticas , Adulto Joven , Adolescente , Humanos , Neoplasias Pancreáticas/epidemiología , Factores de Riesgo , Uso de Tabaco , África , Incidencia , Salud Global , Carga Global de Enfermedades , Años de Vida Ajustados por Calidad de VidaRESUMEN
Pressure ulcers (PUs) are economically burdensome medical conditions. Early changes in pressure ulcers are associated with erythema. In this study, bioelectrical impedance was used to measure the differences between PUs and blanchable erythema. We divided 21 ICR mice into three groups: control, 1000 mmHg-1h, and 1000 mmHg-6h. Healthy skin, blanchable erythema, and PUs were induced on the dorsal skin. The results indicated an immediate increase in impedance, resistance, and reactance values in the pressure group after release, followed by a subsequent decrease until two days after release. Compared with the control group, impedance and reactance significantly increased by 30.9% (p < 0.05) and 30.1% (p < 0.01), respectively, in the 6 h-loading group immediately after release. One and two days after release, the 1 h-loading and 6 h-loading groups exhibited significantly different degrees of decline. One day after release, impedance and resistance decreased by 30.2% (p < 0.05) and 19.8% (p < 0.05), respectively, in the 1 h-loading group; while impedance, resistance, and reactance decreased by 39.2% (p < 0.01), 26.8% (p < 0.01), and 45.7% (p < 0.05), respectively, in the 6 h-loading group. Two days after release, in the 1 h-loading group, impedance and resistance decreased by 28.3% (p < 0.05) and 21.7% (p < 0.05), respectively; while in the 6 h-loading group, impedance, resistance, and reactance decreased by 49.8% (p < 0.001), 34.2% (p < 0.001), and 59.8% (p < 0.01), respectively. One and two days after release the pressure group reductions were significantly greater than those in the control group. Additionally, we monitored changes during wound healing. Distinguishing early PUs from blanchable erythema by noninvasive bioelectrical impedance technology may have applications value in early assessment of PUs.
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Modelos Animales de Enfermedad , Impedancia Eléctrica , Eritema , Ratones Endogámicos ICR , Úlcera por Presión , Cicatrización de Heridas , Animales , Úlcera por Presión/fisiopatología , Impedancia Eléctrica/uso terapéutico , Eritema/fisiopatología , Eritema/etiología , Ratones , Cicatrización de Heridas/fisiología , MasculinoRESUMEN
Objective: To investigate the role of the Abdominal Aortic Calcification-8 (AAC-8) scoring system in predicting restenosis or occlusion of lower extremity arteries after dilatation and angioplasty with drug-coated balloon (DCB). Methods: In this retrospective study, 62 patients who underwent dilatation and angioplasty with DCB for lower limb atherosclerotic obliterans (ASO) were enrolled from September 2018 to June 2022 in Nanjing Drum Tower Hospital Affiliated to Nanjing University Medical School. Among them who aged (73.9±11.3) years, 37 were males and 25 were females. Patients were divided into two groups according to the condition of the lower extremity arteries after dilatation and angioplasty with DCB: recurrence group (n=26) and patency group (n=36). Logistic regression was used to analyze the factors associated with restenosis or occlusion of lower extremity arteries after dilatation and angioplasty with DCB. The predictive value of the AAC-8 score for restenosis or occlusion of the lower extremity arteries after dilatation and angioplasty with DCB was analyzed using the receiver operating characteristic curves (ROC curves). Results: The postoperative follow-up was 16.30 (10.97, 24.10) months in the patency group and 9.03 (6.98, 15.31) months in the recurrence group. The results of multifactorial logistic regression analysis showed that an elevated AAC-8 score (OR=1.388, 95%CI: 1.067-1.806, P=0.015) was an associated factor of restenosis or occlusion of the lower extremity arteries after dilatation and angioplasty with DCB. The ROC curve analysis showed that the area under the curve (AUC) of the AAC-8 score for predicting restenosis or occlusion of the lower extremity arteries after dilatation and angioplasty with DCB was 0.687 (95%CI: 0.550-0.824, P=0.013), with a cut-off value of 5.5 points, a sensitivity of 65.4% and a specificity of 69.5%. Conclusions: Elevated AAC-8 score is associated with restenosis or occlusion of the lower extremity arteries after dilatation and angioplasty with DCB. When the cut-off value is 5.5, the AAC-8 score predicts restenosis or occlusion of the lower extremity arteries after DCB dilation and angioplasty with a sensitivity of 65.4% and a specificity of 69.5%.
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Angioplastia de Balón , Enfermedad Arterial Periférica , Masculino , Femenino , Humanos , Dilatación , Estudios Retrospectivos , Resultado del Tratamiento , Angioplastia , Arteria Femoral/cirugía , Arteria Poplítea/cirugía , Extremidad InferiorRESUMEN
Objective: To investigate the correlation between perivascular fat density (PFD) and plaque stability in patients with carotid artery stenosis. Methods: Clinical data of 110 patients with carotid artery stenosis treated at Drum Tower Hospital, Nanjing University Medical School from January 2018 to December 2022 were retrospectively collected. Based on pathological results of carotid plaque specimens obtained from carotid endarterectomy (CEA), patients were categorized into stable plaque group (n=51) and vulnerable plaque group (n=59). All patients underwent preoperative carotid CT angiography (CTA) to measure PFD at the narrowest carotid artery. Preoperative levels of interleukin-6 (IL-6) and other hematological parameters were collected. Multivariable logistic regression analysis was used to identify factors associated with plaque stability in carotid artery stenosis patients. Area under the curve (AUC) of receiver operating characteristic (ROC) was performed to evaluate the predictive value of PFD for plaque stability. Results: The stable plaque group consisted of 43 males and 8 females with a mean age of (67.6±9.0) years, while the vulnerable plaque group comprised 48 males and 11 females with a mean age of (69.3±9.0) years. The proportions of smokers were 31.4% (16/51) and 50.8% (30/59) in the stable and vulnerable plaque groups, respectively. The proportions of patients with diabetes were 33.3% (17/51) and 52.5% (31/59), respectively. IL-6 levels were 3.46(2.67, 5.34) and 4.51(3.62, 5.51) ng/L in the stable and vulnerable groups, respectively. Mean PFD values were (-69.04±5.35) and (-63.24±6.08) HU, respectively, with maximum PFD values of (-62.90±6.98) and (-56.93±5.90) HU, respectively. The differences were statistically significant (all P<0.05). Multivariable logistic regression analysis showed that increased mean PFD (OR=1.167, 95%CI: 1.029-1.324, P=0.016) and elevated IL-6 levels (OR=1.489, 95%CI: 1.151-1.926, P=0.002) were associated with vulnerability of carotid artery plaques. ROC curve analysis results showed that a cut-off value of -65.5 HU, the AUC for predicting plaque stability based on the mean PFD was 0.756 (95%CI: 0.667-0.844, P<0.001), with sensitivity of 64.4% and specificity of 74.5%. Conclusion: Increased mean PFD at the narrowest carotid artery is associated with vulnerability of plaques in patients with carotid artery stenosis.
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Tejido Adiposo , Estenosis Carotídea , Interleucina-6 , Placa Aterosclerótica , Humanos , Masculino , Femenino , Anciano , Estudios Retrospectivos , Interleucina-6/sangre , Interleucina-6/metabolismo , Persona de Mediana Edad , Arterias Carótidas/patología , Endarterectomía Carotidea , Angiografía por Tomografía Computarizada , Factores de Riesgo , Curva ROC , Modelos LogísticosRESUMEN
Objective: To explore the antiviral activity of the small-molecule compound AM679 in hepatitis B virus (HBV) replication and infection cell models. Methods: The positive regulatory effect of AM679 on EFTUD2 expression was validated by qPCR and Western blotting. HepAD38 and HepG2-NTCP cells were treated with AM679 (0.5, 1, and 2 nmol/L). Negative control, positive control, and AM679 combined with the entecavir group were set up. HBV DNA intra-and extracellularly, as well as the expression levels of intracellular HBV total RNAs and 3.5kb-RNA changes, were detected with qPCR. Hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg) levels were measured in the cell supernatant by an enzyme-linked immunosorbent assay (ELISA). The t-test method was used for the statistical analysis of the mean difference between groups. Results: EFTUD2 mRNA and protein expression levels were significantly increased in HepAD38 and HepG2-NTCP cells following AM679 treatment, with a statistically significant difference (Pâ <â 0.001). Intra-and extracellular indicators such as HBV DNA, HBV RNAs, HBV 3.5kb-RNA, HBsAg, and HBeAg were decreased to varying degrees in both cell models, and the decrease in these indicators was more pronounced with the increase in AM679 concentration and prolonged treatment duration, while the combined use of AM679 and entecavir had a more significant antiviral effect. The HBV DNA inhibition rates in the supernatant of HepAD38 cells with the use of 2 nmol/L AM679 were 21% and 48% on days three and nine, respectively. The AM679 combined with the ETV treatment group had the most significant inhibitory effect (62%), with a Pâ <â 0.01. More active HBV replication was observed after silencing EFTUD2, while the antiviral activity of AM679 was significantly weakened. Conclusion: AM679 exerts anti-HBV activity in vitro by targeting the regulation of EFTUD2 expression.
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Antivirales , Virus de la Hepatitis B , Replicación Viral , Humanos , Antivirales/farmacología , ADN Viral , Guanina/análogos & derivados , Células Hep G2 , Antígenos e de la Hepatitis B/metabolismo , Antígenos de Superficie de la Hepatitis B/metabolismo , Virus de la Hepatitis B/efectos de los fármacos , Replicación Viral/efectos de los fármacos , Indoles/química , Indoles/farmacología , Ácidos Pentanoicos/química , Ácidos Pentanoicos/farmacología , Factores de Elongación de Péptidos/antagonistas & inhibidores , Factores de Elongación de Péptidos/metabolismo , Ribonucleoproteína Nuclear Pequeña U5/antagonistas & inhibidores , Ribonucleoproteína Nuclear Pequeña U5/metabolismoRESUMEN
Objective: To investigate the correlation between brain iron deposition and cognitive function in patients with carotid atherosclerosis stenosis (CAS) based on quantitative susceptibility mapping (QSM). Methods: This single-center prospective study was performed at the Department of Vascular Surgery, Nanjing Drum Tower Hospital from January 2022 to June 2022. Patients who met the ataxation criteria were divided into the CAS group (n=16) and the CAS with mild cognitive impairment (CAS-MCI) group (n=17) according to the Montreal Cognitive Assessment (MoCA) scores. All patients completed QSM imaging and whole-brain analyses were performed for absolute susceptibility values in cortical regions. Age, sex, education years, hypertension, and diabetes mellitus were included as covariates in all analyses. Partial correlation analyses were used to determine the correlation between bilateral CAS degrees and cortical susceptibility values. Further, mediation analyses were performed to determine whether and how cortical susceptibility values affect cognition in CAS patients. Receiver operating characteristic (ROC) curve analysis was also performed to evaluate the predictive worth of differential brain region susceptibility values for cognitive decline. Independent sample t test and Mann-Whitney U test was used to compare quantitative variables. The comparison of categorical variables was conducted using χ2 test, Fisher's exact test or Wilcoxon rank sum test. Results: A total of 33 patients were included in the study, including 16 in the CAS group and 17 in the CAS-MCI group. There were 23 males and 10 females, aged (62.8±9.0) years (range: 48 to 88 years). CAS-MCI group showed higher right CAS grades (Z=-2.037, P=0.042). Whole-brain cortical QSM analyses showed higher susceptibility values in the frontal pole ((-0.210±0.080)×10-8 vs.(-0.130±0.120)×10-8;t=-2.187, P=0.037), superior frontal gyrus ((-0.604±0.243)×10-8 vs. (-0.428±0.203)×10-8;t=-2.223,P=0.034), and temporal pole ((-0.081±0.115)×10-8 vs. (0.054±0.190)×10-8;t=-2.417, P=0.022) in CAS-MCI group compared to CAS group. The susceptibility value of the frontal pole showed a positive correlation with the right CAS grade (r=0.424, P=0.009),while a quasi-significant positive correlation with the left CAS (r=0.313, P=0.070). The susceptibility values of the frontal and temporal poles were negatively correlated with the MoCA score (frontal pole: r=-0.391, P=0.027; temporal pole: r=-0.410, P=0.020). Mediation analysis showed the effect of right CAS on cognition was fully mediated by the susceptibility value of the frontal pole. The ROC curve revealed that the area under the curve of using hypertension combined with the susceptibility value of the frontal pole to predict cognitive decline was 0.882 (95% CI:0.763 to 0.989) with 82% of sensitivity and 83% of specificity. Conclusions: Multiple cortical regions show iron deposition in CAS-MCI patients. Right CAS plays an important role in cognitive decline, frontal pole iron deposition mediates the effect of right CAS on cognitive function. Quantified frontal pole susceptibility is useful for the diagnosis of cognitive decline in patients with CAS.
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Estenosis Carotídea , Disfunción Cognitiva , Hierro , Humanos , Estudios Prospectivos , Estenosis Carotídea/metabolismo , Estenosis Carotídea/complicaciones , Disfunción Cognitiva/etiología , Disfunción Cognitiva/metabolismo , Hierro/metabolismo , Masculino , Imagen por Resonancia Magnética , Femenino , Lóbulo Frontal/metabolismo , Cognición , Anciano , Persona de Mediana EdadRESUMEN
Objective: To investigate the effect of long-term oral aspirin on the changes in the aneurysm sac and persistent type â ¡ endoleak after endovascular aortic repair (EVAR) of infrarenal abdominal aortic aneurysms based on propensity score-matched analysis. Methods: A retrospective cohort study was used to analyze the clinical data of 133 patients with infrarenal abdominal aortic aneurysms treated with EVAR from January 2019 to December 2021 in the Department of Vascular Surgery, Nanjing Drum Tower Hospital. There were 113 males and 20 females, aged (74.8±7.2) years (range: 59 to 95 years). Patients were divided into the group receiving aspirin (n=80) and the group not taking aspirin (n=53) based on whether they took aspirin regularly for a long time after surgery. The two groups were matched in a 1â¶1 ratio using propensity score matching and the caliper value was 0.05. Cumulative probability curve was plotted using the Kaplan-Meier method and the Log-rank test was used to compare the differences in primary endpoint events (enlargement of the aneurysm sac, occurrence of persistent type â ¡ endoleak) and secondary endpoint events (adverse cardiovascular events and clinically relevant bleeding events) between the two groups. Results: A matched cohort was established after propensity score matching, resulting in 32 cases per group. The survival analysis found that the rate of aneurysm sac enlargement was significantly higher in the group receiving aspirin than in the group not taking aspirin (P=0.010), and the incidence of persistent type â ¡ endoleak was significantly higher than that in the group not taking aspirin (P=0.019). The incidence of adverse cardiovascular events and clinically relevant bleeding events were not significantly different in two groups (P=0.061,P=0.286). Conclusions: The risk of aneurysm sac expansion and persistent type â ¡ endoleak were significantly higher in patients taking long-term aspirin after EVAR than in the group not taking asprin. Therefore, high-risk abdominal aortic aneurysm (AAA) patients who are prone to aneurysm sac expansion should be evaluated in advance so that the risks and benefits of surgery can be comprehensively evaluated and treatment strategies can be optimized.
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PURPOSE: Cervical cancer remains a leading cause of cancer death in women. While immunotherapy has shown great success in combating cancer, the value of immunotherapy in cervical cancer is still only beginning to be explored. Thus, we performed a prospective analysis of patient blood and tumor samples at the beginning and end of conventional chemoradiation to assess changes in the immune cell and immunoreceptor compartments, and investigate if and when the addition of immunotherapy could be beneficial. METHODS: Patients with FIGO II-III cervical cancer receiving standard chemoradiation between January 2020 and December 2021 were included. We collected tumor and blood samples from patients before and at the end of therapy and analyzed immune cell composition and immune checkpoint receptor expression on both immune and tumor cells using multicolor flow cytometry. RESULTS: In all, 34 patients were eligible in the study period; 22 could be included and analyzed in this study. We found that chemoradiation significantly reduces T cell numbers in both tumors and blood, but increases macrophage and neutrophil numbers in tumors. Furthermore, we found that the percentage of immune checkpoint receptor PD1 and TIGIT-expressing cells in tumors was significantly reduced at the end of therapy and that CD4 and CD8 memory T cell populations were altered by chemoradiation. In addition, we observed that while PD-L1 expression intensity was upregulated by chemoradiation on blood CD8 cells, PD-L1 expression frequency and the expression intensity of antigen-presenting molecule MHCI were significantly reduced on tumor cells. CONCLUSION: Our data demonstrate that chemoradiation significantly alters the immune cell composition of human cervical tumors and the expression of immune checkpoint receptors on both lymphocytes and tumor cells. As our results reveal that the percentage of PD1+ CD8 cells in the tumor as well as the frequency of PD-L1-expressing tumor cells were reduced at the end of therapy, neoadjuvant or simultaneous anti-PD1 or anti-PD-L1 treatment might provide better treatment efficiency in upcoming clinical studies.
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Neoplasias del Cuello Uterino , Humanos , Femenino , Neoplasias del Cuello Uterino/terapia , Linfocitos T CD8-positivos , Quimioradioterapia , Inmunoterapia/métodos , Microambiente TumoralRESUMEN
The diffuse Galactic γ-ray emission, mainly produced via interactions between cosmic rays and the interstellar medium and/or radiation field, is a very important probe of the distribution, propagation, and interaction of cosmic rays in the Milky Way. In this Letter, we report the measurements of diffuse γ rays from the Galactic plane between 10 TeV and 1 PeV energies, with the square kilometer array of the Large High Altitude Air Shower Observatory (LHAASO). Diffuse emissions from the inner (15°
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Screening and early diagnosis and treatment have been proven effective in reducing the incidence and mortality of colorectal cancer. Colonoscopy combined with pathological examination is the gold standard for colorectal cancer screening. However, due to the invasiveness, high cost and the need for professional endoscopists of colonoscopy, it is not feasible to directly use this method for mass population screening. Fecal immunochemical test (FIT) is one of the screening techniques recommended by authoritative international guidelines for colorectal cancer screening, and has been widely used in population-based colorectal cancer screening programs in countries around the world. This paper elaborates on the value of FIT in colorectal cancer screening from different aspects, such as the technical principles, the screening efficiency, the screening strategies, and the population effects and benefits. Additionally, it describes the current situation of colorectal cancer screening in China and summarizes the challenges faced in colorectal cancer screening in order to optimize the FIT-based colorectal cancer screening strategies in the population and provide theoretical reference for effective colorectal cancer screening.
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Neoplasias Colorrectales , Detección Precoz del Cáncer , Humanos , Detección Precoz del Cáncer/métodos , Colonoscopía , Tamizaje Masivo , Neoplasias Colorrectales/patología , Sangre OcultaRESUMEN
Objective: To evaluate the participation rate and detection of colorectal neoplasms based on annual fecal immunochemical testing (FIT) for three consecutive years in a population-based colorectal cancer screening program in China. Methods: Based on a population-based colorectal cancer screening program conducted from May 2018 to May 2021 in 6 centers in China, 7 793 eligible participants aged 50-74 were included and offered free FIT and colonoscopy (for those who were FIT-positive on initial screening). At baseline, all participants were invited to receive FIT. In subsequent screening rounds, only FIT-positive participants who did not undergo colonoscopy or FIT-negative participants were invited to have repeated FIT screening. FIT-positive participants were recommended to undertake colonoscopy and pathological examination (if abnormalities were found during colonoscopy). An overall of three rounds of annual FIT screening were conducted. The primary outcomes of the study were the participation rate of FIT screening, the compliance rate of colonoscopy for FIT-positive participants, and the detection rate of colorectal neoplasms. Results: Among the 7 793 participants included in this study, 3 310 (42.5%) were male, with age of (60.50±6.49) years. The overall participation rates for the first, second and third round of FIT screening were 94.0%(7 327/7 793), 86.8% (6 048/6 968) and 91.3% (6 113/6 693), respectively. Overall, 7 742 out of 7 793 participants (99.3%) attended at least one round of screening, and 5 163 out of 7 793 participants (66.3%) attended all three rounds of screening. The positivity rate was significantly higher in the first (14.6%, 1 071/7 327) round compared with the second (5.6%, 3 41/6 048) and third (5.5%, 3 39/6 113) screening rounds (P<0.001). The overall compliance rates of colonoscopy examination among FIT-positive subjects were over 70% in three rounds, which were 76.3% (817/1 071), 75.7% (258/341) and 71.7% (243/339), respectively. In a multivariate logistic regression model considering factors including sex, education background, smoking, alcohol drinking, previous colonoscopy examination, colonic polyp history and family history of colorectal cancer among first-degree relatives, gender and smoking status were related factors affecting the participation rate of FIT screening, with higher rate in males and non-smokers. In addition, logistic regression analysis also found that age was negatively correlated with the compliance rate of colonoscopy in FIT positive patients. The detection rate of advanced tumors (colorectal cancer + advanced adenoma) declined from the first round to subsequent rounds [1st round: 1.15% (90/7 793); 2nd round: 0.57% (40/6 968); and 3rd round: 0.58% (39/6 693)], however, the positive predictive value for advanced neoplasms increased round by round, and was 11.02% in the first screening round, 15.50% in the second screening round, and 16.05 % in the third screening round. In each screening round, the detection rate for advanced neoplasms was higher in men than that in women, and increased with age. Conclusions: Annual repeated FIT screening has high acceptance and satisfying detection rates in the Chinese population. To optimize and improve the effectiveness of colorectal cancer screening, multi-round repeated FIT screening should be implemented while ensuring high participation rates.
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Adenoma , Neoplasias Colorrectales , Humanos , Masculino , Femenino , Detección Precoz del Cáncer , Valor Predictivo de las Pruebas , Colonoscopía , Tamizaje Masivo , Adenoma/diagnóstico , Neoplasias Colorrectales/patologíaRESUMEN
Objective: To investigate the effect of different respiratory motion correction methods on PET images during chest PET/MRI scans. Methods: The data of 35 patients (24 males and 11 females, aged from 29 to 84 year) of pulmonary lesions with significantly high uptake in thoracic PET/MRI scan were retrospective collected from Jingling Hospital. Four different methods were used to reconstruct the PET data. Group A was the full-time 20 min without respiratory motion correction static acquisition (Static) as a control, group B was the end-expiration static collection (Q.Static), and group C was the multi-bins respiratory gating (Gated-Respiratory). In addition, the influence of the time being considered, group D was added for reconstruction in the first 1/3 period (6 min 40 s) of group A. Then, the maximum value (L-SUVmax) and the mean value (L-SUVmean) of the SUV of the lesion, the mean value (B-SUVmean) and the standard deviation (B-SUVsd) of the SUV of the background under each reconstruction results were measured, and for each lesion the signal-to-noise ratio (L-SNR) was calculated. In order to exclude the interference of the background, the mean of the relative SUV (L-dSUVmean) of the L-SUVmean relative to the B-SUVmean was also calculated. Finally, One-Way Repeated Measures ANOVA was used, and the post-hoc pairwise comparison between groups was tested by Bonferroni's modified test. Results: There was statistically significant difference among group B or group C compared to group A and group D in L-SUVmax, L-SUVmean and L-dSUVmean [L-SUVmax:group B vs group A or group D was 8.06±3.57 vs 7.73±3.45 or 7.61±3.50, group C vs group A or group D was 8.04±3.56 vs 7.73±3.45 or 7.61±3.50 (all P<0.05); L-SUVmean: group B vs group A or group D was 4.12±1.78 vs 3.98±1.72 or 3.91±1.71, group C vs group A or group D was 4.13±1.78 vs 3.98±1.72 or 3.91±1.71 (all P<0.05); L-dSUVmean: group B vs group A or group D was 3.52±0.16 vs 3.39±0.18 or 3.31±0.18, group C vs group A or group D was 3.53±0.18 vs 3.39±0.18 or 3.31±0.18 (all P<0.05)], but there was no statistically significant difference between group B and group C (all P>0.05). There were statistically significant differences between group D and group A in B-SUVsd (0.07±0.00 vs 0.07±0.00, P=0.023) and L-SNR (69.80±44.57 vs 85.35±68.98, P=0.001). There was no statistically significant difference between group D and group A in L-SUVmax, L-SUVmean, B-SUVmean and L-dSUVmean (all P>0.05). Conclusions: There was no significant difference in PET image quality between the Q.static and Gated-Respiratory group, both of the two groups were better than the Static group which with no Gated-Respiratory motion correction. If non-respiratory gated Static is used, the PET acquisition time is recommended to be 6 min 40 s.
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Imagen por Resonancia Magnética , Tomografía de Emisión de Positrones , Femenino , Masculino , Humanos , Estudios Retrospectivos , Radiografía , TóraxRESUMEN
Objective: To explore the association between gallbladder adenomyomatosis (GA) and occult pancreaticobiliary reflux (OPBR). Methods: A total of 81 patients with GA who underwent cholecystectomy in Shanghai East Hospital from December 2020 to January 2022 were enrolled, including 48 cases of fundal type, 28 cases of segmental type and 5 cases of diffuse type. Patient's intraoperative bile was coltected and tested for amylase. According to gallbladder bile amylase level, patients were divided into OPBR group (bile amylase>110 U/L) and the control group (bile amylase≤110 U/L). Results: Among 81 patients, 32 were male and 49 were female, and aged (49.1±13.2) years; there were 66 cases in control group, including 27 males and 39 females, and aged (50.0±12.9)years; there were 15 patients in the OPBR group, including 5 males and 10 females, and aged (45.1±14.2) years. In terms of the clinical features of the two groups, there was no significant difference (all P>0.05), except for a significant increase in biliary amylase in the OPBR group compared with the control group (P<0.001). However, the incidence of OPBR was significantly different in the three types of GA, with a lower incidence of OPBR in the fundal type (10.4%, 5/48) than in the segmental type (28.6%, 8/28) and diffuse type (2/5) (P=0.038). In addition, segmental GA was more likely to be combined with gallbladder stones (85.7%, 24/28) than fundal GA (58.3%, 28/48) and diffuse GA (3/5) (P=0.031). Univariate and multivariate logistic regression analyses showed OPBR [OR (95%CI)=3.410 (1.010 to 11.513), P=0.048] and combined gallbladder stones [OR (95%CI)=2.974 (1.011 to 8.745), P=0.048] indepenclently correlated with segmental and diffuse GA. Conclusions: The incidence of OPBR is higher in segmental and diffuse GA, and gallstones and OPBR are independently associated with the occurrence of segmental and diffuse GA. These results suggest that OPBR may be the initiating factor for the occurrence and carcinogenesis of segmental and diffuse GA.
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Neoplasias de la Vesícula Biliar , Cálculos Biliares , Humanos , Masculino , Femenino , Vesícula Biliar/química , Vesícula Biliar/cirugía , Neoplasias de la Vesícula Biliar/complicaciones , Neoplasias de la Vesícula Biliar/cirugía , China , Bilis , Cálculos Biliares/complicaciones , Amilasas/análisisRESUMEN
To explore whether PPARA is involved in the process of ferroptosis in hepatoma cells, peroxisome proliferator activated receptor (PPARA) was comprehensively analyzed in hepatocellular carcinoma (HCC) through public database and experimental data, including the expression, the functions and the potential roles of tumor progression. The research design is experimental research,data analysis based on bioinformatics and cell experiment. From January 2022 to August 2022, relevant cell experiments were conducted in the Basic Medical Laboratory of the General Hospital of the Southern Theatre of the Chinese People's Liberation Army. The expression and the correlation with clinicopathologic features of PPARA in HCC were analyzed by The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. To study the protein expression of PPARA in HCC and normal tissues through the Human Protein Atlas (HPA). The protein-protein interaction (PPI) network between PPARA and the core factor of ferroptosis was constructed based on Search Tool for the Retrival of Interacting Genes/Protein (STRING) database, then, the correlation between PPARA and the core gene Glutamate-cysteine Ligase Catalytic Subunit (GCLC) was analyzed by Gene Expression Profiling Interactive Analysis (GEPIA). Assessed the expression of PPARA in HCC cell lines SK-HEP-1, SMMC-7721, MHCC-97H, BEL-7402 and normal liver cell L02 by Western Blot (WB) and the changes of PPARA expression after 48h treatment with ferroptosis inducer Erastin were observed. Single factor analysis of variance was used to compare the expression of PPARA between groups in GEPIA database. The expression of PPARA in GSE25097 and GSE112790 data was compared by rank sum test. Survival analysis was performed using time series test method. The difference of PPARA expression between clinical and pathological features was compared using the Kruskal-Wallis test. The correlation between the expression of GCLC and PPARA was compared by the method of Spearman correlation. The expression of PPARA in cell lines was compared by paired T test. The results showed that the RNA and protein expression of PPARA in HCC was lower than that in normal tissues (P<0.05). PPARA alterations were correlated with patient clinicopathological features and prognosis (P<0.05). The PPI constructed by STRING database suggests that PPARA interact with the key factors of ferroptosis, such as NFE2 like bZIP transcription factor 2 (NFE2L2), Heme Oxygenase 1 (HMOX1), Tumor Protein P53 (TP53), GCLC, Dipeptidyl Peptidase 4 (DPP4), Citrate Synthase (CS), Arachidonate 15-Lipoxygenase (ALOX15) and Acyl-CoA Synthetase Long Chain Family Member 4 (ACSL4). Furthermore, the PPARA was significantly associated with GCLC validated via GEPIA database(R=0.6, P<0.05). The expression of PPARA increased after treatment with ferroptosis inducer Erastin for 48 h by WB. In conclusion, the expression of PPARA is lower in HCC with a poor prognosis. PPARA interacts with GCLC in regulating ferroptosis in HCC.
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Carcinoma Hepatocelular , Ferroptosis , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patología , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patología , Receptores Activados del Proliferador del Peroxisoma/genéticaRESUMEN
Objective: To investigate the association between the urinary arsenic level and serum total testosterone in Chinese men aged 18 to 79 years. Methods: A total of 5 048 male participants aged 18 to 79 years were recruited from the China National Human Biomonitoring (CNHBM) from 2017 to 2018. Questionnaires and physical examinations were used to collect information on demographic characteristics, lifestyle, food intake frequency and health status. Venous blood and urine samples were collected to detect the level of serum total testosterone, urinary arsenic and urinary creatinine. Participants were divided into three groups (low, middle, and high) based on the tertiles of creatinine-adjusted urinary arsenic concentration. Weighted multiple linear regression was fitted to analyze the association of urinary arsenic with serum total testosterone. Results: The weighted average age of 5 048 Chinese men was (46.72±0.40) years. Geometric mean concentration (95%CI) of urinary arsenic, creatinine-adjusted urinary arsenic and serum testosterone was 22.46 (20.08, 25.12) µg/L, 19.36 (16.92, 22.15) µg/g·Cr and 18.13 (17.42, 18.85) nmol/L, respectively. After controlling for covariates, compared with the low-level urinary arsenic group, the testosterone level of the participants in the middle-level group and the high-level group decreased gradually. The percentile ratio (95%CI) was -5.17% (-13.14%, 3.54%) and -10.33% (-15.68%, -4.63). The subgroup analysis showed that the association between the urinary arsenic level and testosterone level was more obvious in the group with BMI<24 kg/m2 group (Pinteraction=0.023). Conclusion: There is a negative association between the urinary arsenic level and serum total testosterone in Chinese men aged 18 to 79 years.