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OBJECTIVE: In 2016, the ESMO-ESGO-ESTRO consensus included LVSI (Lymph-vascular space invasion, LVSI) status as a risk stratification factor for stage I endometrioid endometrial cancer (EEC) patients and as one of the indications for adjuvant therapy. Furthermore, LVSI is included in the new FIGO staging of endometrial cancer (EC) in 2023. However, the data contribution of the Chinese population in this regard is limited. The present study aimed to further comfirm the influence of LVSI on the prognosis of early-stage low-grade EEC in a fifteen-year retrospective Chinese cohort study. METHODS: This retrospective analysis cohort included 702 EEC patients who underwent TAH/BSO surgery, total abdominal hysterectomy, bilateral salpingooophorectomy in Peking University People's Hospital from 2006 to 2020. Patients were stratified based on LVSI expression status as: LVSI negative group and LVSI positive group. Clinical outcome measures related to LVSI, assessed with a univariate and multivariate Cox proportional hazards regression model. RESULTS: 702 EEC patients with stage I and grade 1-2 were analyzed. 58 patients (8.3%) were LVSI-positive and 14 patients (2.0%) was relapse. Recurrence rates in LVSI-negative and LVSI-positive were 1.6% and 6.9%, respectively. 5-year disease-free survival (DFS) rate in LVSI-negative and LVSI-positive were 98.4% and 93.1%, respectively. These rates for 5-year overall (OS) survival in LVSI-negative were 98.9% while it was 94.8% in LVSI-positive. Multivariate analysis showed that LVSI is an independent risk factor for 5-year DFS (HR = 4.60, p = 0.010). LVSI has a similar result for 5-year OS(HR = 4.39, p = 0.028). CONCLUSIONS: LVSI is an independent predictor of relapse and poor prognosis in early-stage low-grade endometrioid endometrial cancer in the Chinese cohort.
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Carcinoma Endometrioide , Neoplasias do Endométrio , Invasividade Neoplásica , Estadiamento de Neoplasias , Humanos , Feminino , Estudos Retrospectivos , Neoplasias do Endométrio/patologia , Neoplasias do Endométrio/mortalidade , Neoplasias do Endométrio/cirurgia , Pessoa de Meia-Idade , Prognóstico , Carcinoma Endometrioide/patologia , Carcinoma Endometrioide/cirurgia , Carcinoma Endometrioide/mortalidade , Carcinoma Endometrioide/terapia , Taxa de Sobrevida , Seguimentos , China/epidemiologia , Histerectomia/estatística & dados numéricos , Histerectomia/métodos , Gradação de Tumores , Idoso , Metástase Linfática , Vasos Linfáticos/patologia , Adulto , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/epidemiologia , Recidiva Local de Neoplasia/cirurgia , População do Leste AsiáticoRESUMO
Background: A low-clean living environment (LCLE) can increase gut microbial diversity and prevent allergic diseases, whereas gut microbial dysbiosis is closely related to the pathogenesis of asthma. Our previous studies suggested that soil in the LCLE is a key factor in shaping intestinal microbiota. We aimed to explore whether sterilized soil intake as a prebiotic while being incubated with microbes in the air can attenuate mouse asthma inflammation by modifying gut microbiota. Methods: 16S rRNA gene sequencing was used to analyze the gut microbial composition, in combination with immune parameters measured in the lung and serum samples. Results: 16S rRNA gene sequencing results showed significant differences in the fecal microbiota composition between the test and control mice, with a higher abundance of Allobaculum, Alistipes, and Lachnospiraceae_UCG-001, which produce short-chain fatty acids and are beneficial for health in the test mice. Soil intake significantly downregulated the concentrations of IL-4 and IL-9 in serum and increased the expression of IFN-γ, which regulated the Th1/Th2 balance in the lung by polarizing the immune system toward Th1, alleviating ovalbumin-induced asthma inflammation. The effect of sensitization on gut microbiota was greater than that of air microbes and age together but weaker than that of soil. Conclusions: Soil intake effectively reduced the expression of inflammatory cytokines in asthmatic mice, possibly by promoting the growth of multiple beneficial bacteria. The results indicated that the development of soil-based prebiotic products might be used for allergic asthma management, and our study provides further evidence for the hygiene hypothesis.
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BACKGROUND: Pure uterine serous carcinoma (p-USC) and mixed tumors with serous component (m-USC) are aggressive subtypes of endometrial cancer associated with high mortality rates. This retrospective study aimed to compare clinicopathologic features and outcomes of p-USC and m-USC in a single center. METHODS: This study retrospectively reviewed patients diagnosed with USC at Peking University People's Hospital between 2008 and 2022. T-tests and chi-square tests were used to compare clinicopathological characteristics between p-USC and m-USC. Kaplan-Meier survival curve and Cox regression analysis were used to analyze the impact of clinical and pathological variables on OS and PFS. RESULTS: Among the 91 patients who underwent surgery, 65.9% (n = 60) were p-USC, and 34.1% (n = 31) were m-USC. Patients with p-USC had earlier menopause (P = 0.0217), a lower rate of progesterone receptor(PR) expression (P < 0.001), and were more likely to have positive peritoneal cytology (P = 0.0464). After a median follow-up time of 40 months, 28 (46.7%) p-USC and 9 (29%) m-USC patients had progression disease, 18 (30%) and 8 (25.8%) patients died of their disease. 5-year PFSR were 51.2% and 75.3%, respectively, and 5-year OS rates were 66% and 67.4%. Kaplan-Meier survival analysis showed that p-USC was more likely to relapse than m-USC (P = 0.034), but there was no significant difference in OS. Cox regression analysis showed that lymph node metastasis and surgical approach were risk factors for OS, and myoinvasion depth ≥ 1/2 was an independent risk factor for PFS. CONCLUSIONS: p-USC was more likely to relapse than m-USC, but there was no significant difference in OS between the two subtypes.
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Cistadenocarcinoma Seroso , Neoplasias Uterinas , Feminino , Humanos , Estudos Retrospectivos , Recidiva Local de Neoplasia/patologia , Neoplasias Uterinas/patologia , Cistadenocarcinoma Seroso/patologia , Recidiva , Estadiamento de NeoplasiasRESUMO
The decline in gut microbial diversity in modern humans is closely associated with the rising prevalence of various diseases. It is imperative to investigate the underlying causes of gut microbial loss and restoring methods. Although the impact of non-perinatal antibiotic use on gut microbiota has been recognized, its intergenerational effects remain unexplored. Our previous research has highlighted soil in the farm environment as a key factor for gut microbiome health by restoring gut microbial diversity and balance. In this study, we investigated the intergenerational consequences of antibiotic exposure and the therapeutic potential of sterile soil. We treated C57BL/6 mice with vancomycin and streptomycin for 2 weeks continuously, followed by a 4-8 week withdrawal period before breeding. The process was repeated across 3 generations. Half of the mice in each generation received an oral sterile soil intervention. We assessed gut microbial diversity, anxiety behavior, microglial reactivity, and gut barrier integrity across generations. Antibiotic exposure led to a decrease in gut microbial diversity over generations, along with aggravated anxiety behavior, microgliosis, and altered intestinal tight junction protein expression. Oral sterile soil intervention restored gut microbial diversity in adult mice across generations, concomitantly rescuing abnormalities in behavior, microgliosis, and intestinal barrier integrity. In conclusion, this study simulated an important process of the progressive loss of gut microbiota diversity in modern humans and demonstrated the potential of sterile soil to reverse this process. This study provides a theoretical and experimental basis for research and interventions targeting multiple modern chronic diseases related to intestinal microorganisms.
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Antibacterianos , Microbioma Gastrointestinal , Humanos , Animais , Camundongos , Antibacterianos/farmacologia , Solo , Camundongos Endogâmicos C57BLRESUMO
OBJECTIVE: Metabolic syndrome (MetS) is closely related to the increased risk and poor prognosis of endometrial cancer (EC). The purpose of this study was to analyze the relationship between metabolic risk score (MRS) and EC, and establish a predictive model to predict the prognosis of EC. METHODS: A retrospective study was designed of 834 patients admitted between January 2004 to December 2019. Univariate and multivariate Cox analysis were performed to screen independent prognostic factors for overall survival (OS). A predictive nomogram is built based on independent risk factors for OS. Consistency index (C-index), calibration plots and receiver operating characteristic curve were used to evaluate the predictive accuracy of the nomogram. RESULTS: The patients were randomly divided into training cohort (n=556) and validation cohort (n=278). The MRS of EC patients, ranging from -8 to 15, was calculated. Univariate and multivariate Cox analysis indicated that age, MRS, FIGO stage, and tumor grade were independent risk factors for OS (p<0.05). The Kaplan-Meier analysis demonstrated that EC patients with low score showed a better prognosis in OS. Then, a nomogram was established and validated based on the above four variables. The C-index of nomogram were 0.819 and 0.829 in the training and validation cohorts, respectively. Patients with high-risk score had a worse OS according to the nomogram. CONCLUSION: We constructed and validated a prognostic model based on MRS and clinical prognostic factors to predict the OS of EC patients accurately, which may help clinicians personalize prognostic assessments and effective clinical decisions.
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População do Leste Asiático , Neoplasias do Endométrio , Feminino , Humanos , Prognóstico , Estudos Retrospectivos , Fatores de RiscoRESUMO
Ginsenoside Rh3 (GRh3) is a seminatural product obtained by chemical processing after isolation from Chinese herbal medicine that has strong antitumor activity against human tumors. However, its antitumor role remains to be elucidated. The aim of this study is to explore the mechanisms underlying the tumor suppressive activity of GRh3 from the perspective of pyroptosis and ferroptosis. GRh3 eliminates colorectal cancer (CRC) cells by activating gasdermin D (GSDMD)-dependent pyroptosis and suppressing solute carrier family 7 member 11 (SLC7A11), resulting in ferroptosis activation through the Stat3/p53/NRF2 axis. GRh3 suppresses nuclear factor erythroid 2-related factor 2 (NRF2) entry into the nucleus, leading to the decrease of heme oxygenase 1 (HO-1) expression, which in turn promotes NOD-like receptor thermal protein domain associated protein 3 (NLRP3) and caspase-1 expression. Finally, caspase-1 activates GSDMD-dependent pyroptosis. Furthermore, GRh3 prevents NRF2 from entering the nucleus, which suppresses SLC7A11, causing the depletion of glutathione (GSH) and accumulation of iron, lipid reactive oxygen species (ROS) and malondialdehyde (MDA), and eventually leading to ferroptosis in CRC cells. In addition, GRh3 effectively inhibits the proliferation of CRC cells in vitro and in nude mouse models. Collectively, GRh3 triggers pyroptotic cell death and ferroptotic cell death in CRC cells via the Stat3/p53/NRF2 axis with minimal harm to normal cells, showing great anticancer potential.
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Neoplasias Colorretais , Ferroptose , Humanos , Animais , Camundongos , Piroptose , Fator 2 Relacionado a NF-E2/genética , Proteína Supressora de Tumor p53 , Caspase 1 , Glutationa , Camundongos Nus , Neoplasias Colorretais/tratamento farmacológico , Fator de Transcrição STAT3RESUMO
Background: The incidence of cancer-related fatigue (CRF) is increasing, but its lack of clear pathogenesis makes its prevention and treatment difficult. Therefore, it is of great significance to clarify the pathogenesis of CRF and find effective methods to treat it. Methods: The CRF model was established by intraperitoneal injection of LLC cells in ICR mice to explore the pathogenesis of CRF and verify the therapeutic effect of the Yifei-Sanjie pill (YFSJ). The active components of YFSJ were found by LC/MS, the in vitro inflammatory infiltration model of skeletal muscle was constructed by TNF-α and C2C12 myoblasts, and the results of in vivo experiments were verified by this model. Results: Behavioral analysis results showed that YFSJ alleviated CRF; histological examination results showed that YFSJ could reverse the tumor microenvironment leading to skeletal muscle injury; ELISA and RNA-seq results showed that the occurrence of CRF and the therapeutic effect of YFSJ were closely related to the tumor inflammatory microenvironment; IHC and WB results showed that the occurrence of CRF and the therapeutic effect of YFSJ were closely related to the Stat3-related signaling pathway and autophagy. Conclusions: YFSJ can reduce the level of inflammation in the tumor microenvironment in vivo, inhibit the abnormal activation of the Stat3/HIF-1α/BNIP3 signaling pathway induced by tumor-related inflammation, thereby inhibiting the overactivation of mitophagy in skeletal muscle, and finally alleviate CRF. Quercetin, one of the components of YFSJ, plays an important role in inhibiting the phosphorylation activation of Stat3.
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Automatic modulation classification (AMC) is an essential part in a cognitive radio receiver. Benefited from the discriminative constellation characteristics among most modulations, AMC methods based on constellation diagrams usually achieve pleasant performance. However, in noncooperation communication systems, constellation diagrams expressing modulations explicitly are difficult to obtain via blind symbol timing synchronization, especially in complicated wireless channels. Therefore, this article proposes a novel constellation diagram-based AMC architecture called attentive Siamese networks (ASNs) by considering multitiming constellation diagrams (MCDs) and selecting the proper symbol timings at the feature level, which is a more robust way than the conventional signal-level symbol timing synchronization. In detail, convolutional neural networks sharing the same parameters first extract deep feature vectors for MCDs. Then, an attention inference module weights all the deep feature vectors. Finally, AMC is realized based on the weighted feature vectors. Moreover, the ASN architecture can be trained end-to-end. Comparing with the state-of-the-art methods that take diverse representations of received baseband signals as input, experimental results based on the RadioML 2018.01A dataset and non-Gaussian noise dataset demonstrate that ASN achieves a remarkable improvement, whose classification accuracy goes over 99% when the signal-to-noise ratio (SNR) > 10 dB.
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Traditional lithium-sulfur battery catalysts are still facing substantial challenges in solving sulfur redox reactions, which involve multistep electron transfer and multiphase transformations. Here, inspired by the combination of iron dextran (INFeD) and ascorbic acid (VC) as a blood tonic for the treatment of anemia, a highly efficient VC@INFeD catalyst is developed in the sulfur cathode, accomplishing the desolvation and enrichment of high-concentration solvated lithium polysulfides at the cathode/electrolyte interface with the assistance of multiple H/Li-bonds and resolving subsequent sulfur transformations through gradient catalysis sites where the INFeD promotes long-chain lithium polysulfide conversions and VC accelerates short-chain lithium polysulfide conversions. Comprehensive characterizations reveal that the VC@INFeD can substantially reduce the energy barrier of each sulfur redox step, inhibit shuttle effects, and endow the lithium-sulfur battery with high sulfur utilization and superior cycling stability even under a high sulfur loading (5.2 mg cm-2 ) and lean electrolyte (electrolyte/sulfur ratio, ≈7 µL mg-1 ) condition.
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We tune the valence state of single Au atoms anchored on CeO2(100) by treating the catalyst in H2 at different temperatures and obtain a series of Au1/CeO2(100). The transition from Au1+0.9 to Au1+0.3 leads to an enhancement of the CO oxidation activity of Au1/CeO2(100) by one order of magnitude. This work is of significance for an in-depth understanding of reaction mechanisms and rational design of high-performance catalysts.
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The early identification of predictors related to cardiovascular risk factor clustering (CVRFC) in adolescents can help prevent Cardiovascular disease. The hypertriglyceridemic-waist circumference (HTW) phenotype is considered a simple and useful indicator to identify cardiovascular disease. However, there is limited research on the relationship between the HTW phenotype and (CVRFC) in adolescents. It is unclear whether the HTW phenotype can identify early the risk of developing CVRFC in adolescents. The study aimed to examine the association of the HTW phenotype with CVRFC in adolescents. A total of 1478 adolescents aged 12-18 years were classified into normal waist circumference (WC) and normal triglyceride (TG) (NWNT, 66.4%), normal WC and high TG (HTG, 5.5%), enlarged WC and normal TG (EW, 22.2%) and enlarged WC and high TG (HTW, 5.8%). High TG was defined as TG ≥ 1.47 mmol/L and enlarged WC ≥ 90th percentile by gender and age. CVRFs in this study included elevated blood pressure (BP), impaired fasting glucose (IFG), high total cholesterol (TC), low high-density lipoprotein cholesterol (HDL-C), and high low-density lipoprotein cholesterol (LDL-C). CVRFC ≥ 2 or CVRFC ≥ 3 were defined as the presence of at least two or three cardiovascular risk factors. After adjustment for BMI, gender and age, the HTW phenotype increased the risk of CVRFC ≥ 2 and CVRFC ≥ 3 compared to the NTNW phenotype, OR and 95%CI were 2.40 (1.23-4.58) and 3.63 (1.49-8.86), respectively. After stratification by gender, similar results were found in boys, however, girls with the EW phenotype had a lower risk of CVRFC ≥ 2 and CVRFC ≥ 3 compared with the NTNW phenotype after adjustment for BMI and age. The area under the ROC curve was 0.698 (0.661-0.736) and 0.782 (0.725-0.840) when TG was combined with WC to detect cardiovascular risk factors clustering, which was better than BMI, WHtR, TG or WC alone. And similar results were obtained for both boys and girls when stratified by gender. These results revealed that different combinations of TG and WC levels are closely associated with cardiovascular risk factors clustering in both boys and girls, and TG combining WC performed better than BMI, WHtR, TG or WC alone in detecting cardiovascular risk factor clustering in adolescents.
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Doenças Cardiovasculares , Cintura Hipertrigliceridêmica , Doenças Cardiovasculares/etiologia , China , Colesterol , HDL-Colesterol , Análise por Conglomerados , Fatores de Risco de Doenças Cardíacas , Humanos , Cintura Hipertrigliceridêmica/complicações , Fenótipo , Fatores de RiscoRESUMO
Background: The lymph node (LN) is one of the main sites of recurrence in patients with endometrial carcinoma (EC). Literature specifically analyzing LN recurrence (LNR) in EC remains limited in number. Methods: Patients with EC undergoing surgery between 2006 and 2021 in Peking University People's Hospital was included, clinicopathological data of whom were collected and analyzed retrospectively by R 4.0.3. Results: A total of 792 patients were included, with 73 patients having recurrence, among whom 21 patients had LNR. Median recurrence-free survival (RFS) in patients with LNR was 16 [4-39] months. LNR was extensive, with pelvic LNs most commonly involved (9/21). There are various patterns of LNR, with 33.3% (7/21) LN-only recurrence. Multivariable analysis suggested advanced stage, larger tumor diameter and poor histology were independent risk factors for LNR. Patients with LN metastasis (LNM) diagnosed at initial treatment accounted for 47.6% (10/21) of cases with LNR, 60.0% (6/10) of whom had recurrent LNs beyond the region of LNM, 90.0% (9/10) of whom had recurrence nodes overlapping with the range of lymphadenectomy. Uni- and multi-variable analysis suggested lymphadenectomy was not a protective factor for LNR, with both the range and number of LNs harvested considered. Conclusions: LNR is common in patients with EC, with an extensive range and various patterns of recurrence. The International Federation of Gynecology and Obstetrics (FIGO) stage, tumor diameter and histology were independent risk factors for LNR, but lymphadenectomy seemed not a protective factor for LNR.
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The key challenges facing the commercialization of lithium-sulfur (Li-S) batteries are shortening the lithium polysulfide (LiPS) intermediate existence time while accelerating solid-phase conversion reactions. Herein, inspired by highly efficient natural enzymes with Fe/N active sites for oxygen reduction reactions, we report a periodic expansion catalysis concept, i.e., Ru and P synergic stereoselectivity, for designing sulfur reduction reaction (SRR) catalysts. As a proof of concept, a RuP2-configuration molecular catalyst was exploited to assemble an interlayer in Li-S batteries that adsorbs LiPSs, optimizes Li+ migration paths, and catalyzes SRRs. Comprehensive investigation identified the elimination of steric hindrance and strong electron orbital couplings between metallic d band and nonmetallic p band as the main contributing factors of PEC for the SRRs. As a result, the Li-S battery with â¼0.5 wt % catalyst additive showed enhanced cycling stability even under a high sulfur loading (6.5 mg cm-2) and low electrolyte/sulfur ratio (9 µL mg-1).
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OBJECTIVE: To investigate the relationship between serum uric acid and cardiovascular risk factors and cardiovascular risk factor clustering(CVRFC) in children and adolescents in Yinchuan, Ningxia. METHODS: A present study design was adopted, and 1486 children and adolescents aged 10-18 years in urban areas of Yinchuan City were selected as study subjects with a mean age of(14.3±1.4) years in 2015, 2017 to 2018 by stratified clustering sampling, including 728(49.0%) boys, 1157(77.9%) Han, 170(11.4%) Hui and 159(10.7%) from other ethnic groups. All study subjects completed questionnaires, physical measurements and biochemical tests. RESULTS: Hyperuricemia(HUA) was significantly positive associated with abdominal obesity(OR=3.23, 95%CI 2.37-4.40), hypertension(OR=1.64, 95%CI 1.21-2.23), dyslipidemia(OR=1.51, 95%CI 1.17-1.96), CVRFC≥2(OR=3.71, 95%CI 2.80-4.93) and CVRFC≥3(OR=6.92, 95% CI 4.18-11.64)(P<0.05). There was an additive interaction between HUA and gender on cardiovascular risk factors and their aggregation. Compared with non-HUA girls, HUA girls have 3.57 times(95%CI 2.26-5.64) the risk of abdominal obesity, dyslipidemia, CVRFC≥2 and CVRFC≥3, respectively, 1.65 times(95%CI 1.10-2.47), 4.10 times(95%CI 1.10-2.47) and 7.63 times(95%CI 3.67-15.89). HUA boys have 1.75 times(95%CI 1.16-2.65) the risk of abdominal obesity, dyslipidemia, CVRFC≥2 and CVRFC≥3, respectively, 2.14(95%CI 1.51-3.03) times, 4.27 times(95%CI 2.98-6.13) and 7.97 times(95%CI 4.11-15.44), (P<0.05). CONCLUSION: Hyperuricemia was significantly positive associated with cardiovascular risk factors and their aggregation in children and adolescents in Yinchuan, and there was an additive interaction between hyperuricemia and gender.
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Doenças Cardiovasculares , Ácido Úrico , Adolescente , Doenças Cardiovasculares/epidemiologia , Criança , Análise por Conglomerados , Feminino , Fatores de Risco de Doenças Cardíacas , Humanos , Masculino , Fatores de RiscoRESUMO
Traditional farm environments induce protection from allergic diseases. In this study, farm environmental factors were classified into three categories, environmental microbes, soil, and organic matter. To explore the impact of soil and environmental microorganisms on gut microbiota and immune function, mice were fed sterilized soil and inhaling microbes, soil microbes, or non-sterilized soil. Metagenomic sequencing results showed the intake of sterile soil, that is, inhaling a small amount of soil microbes in the air increased gut microbial diversity and the abundance of type III secretion system (T3SS) genes, and decreased serum immune IgE levels induced by 2-4-dinitrofluorobenzene (DNFB). The intake of soil microbes increased the abundance of genes involved in the metabolism of short-chain fatty acids and amino acid biosynthesis. Meanwhile, the intake of soil increased gut microbial diversity, the abundance of T3SS genes and related infectious elements, and genes associated with the metabolism of short-chain fatty acids and amino acid biosynthesis, and decreased serum IgE levels. Therefore, soil may be useful as a potential 'prebiotic' promoting the reproduction and growth of some intestinal microorganisms that harbour bacterial secretion system genes, especially those of T3SS, whose abundance was positively and significantly correlated with innate immune function of mice.
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Microbioma Gastrointestinal , Aminoácidos , Animais , Dinitrofluorbenzeno , Ácidos Graxos Voláteis , Microbioma Gastrointestinal/genética , Imunoglobulina E , Camundongos , Solo/química , Sistemas de Secreção Tipo IIIRESUMO
Diabetes is closely related to the occurrence of endometrial cancer (EC) and its poor prognosis. However, there is no effective clinical treatment for EC patients with diabetes (patientEC+/dia+ ). To explore new therapeutic targets, Ishikawa is cultured with high glucose (IshikawaHG ) mimicking hyperglycemia in patientEC+/dia+ . Subsequently, it is discovered that IshikawaHG exhibits glucose metabolic reprogramming characterized by increased glycolysis and decreased oxidative phosphorylation. Further, pyruvate dehydrogenase kinase 1 (PDK1) is identified to promote glycolysis of IshikawaHG by proteomics. Most importantly, JX06, a novel PDK1 inhibitor combined metformin (Met) significantly inhibits IshikawaHG proliferation though IshikawaHG is resistant to Met. Furthermore, a reduction-sensitive biodegradable polymer is adopted to encapsulate JX06 to form nanoparticles (JX06-NPs) for drug delivery. It is found that in vitro JX06-NPs have better inhibitory effect on the growth of IshikawaHG as well as patient-derived EC cells (PDC) than JX06. Additionally, it is found that JX06-NPs can accumulate to the tumor of EC-bearing mouse with diabetes (miceEC+/dia+ ) after intravenous injection, and JX06-NPs combined Met can significantly inhibit tumor growth of miceEC+/dia+ . Taken together, the study demonstrates that the combination of JX06-NPs and Met can target the cancer metabolism plasticity, which significantly inhibits the growth of EC, thereby provides a new adjuvant therapy for patientsEC+/dia+ .
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Diabetes Mellitus , Neoplasias do Endométrio , Metformina , Nanopartículas , Animais , Linhagem Celular Tumoral , Proliferação de Células , Dissulfiram/análogos & derivados , Neoplasias do Endométrio/complicações , Neoplasias do Endométrio/tratamento farmacológico , Neoplasias do Endométrio/metabolismo , Feminino , Humanos , Metformina/farmacologia , Metformina/uso terapêutico , Camundongos , MorfolinasRESUMO
OBJECTIVES: The association between metabolically healthy overweight/obesity (MHO) and inflammatory markers remains controversial. The aim of the present study was to describe the prevalence of different metabolic phenotypes and to examine the relationship of different metabolic phenotypes with inflammatory markers among Chinese children and adolescents. METHODS: The study included 1,125 children and adolescents aged 10-18 years using a cross-sectional survey, and all subjects were classified into four groups based on a combination of BMI and metabolic status. In addition, the inflammatory markers we measured were high-sensitivity C-reactive protein (hs-CRP), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6). RESULTS: The prevalence of metabolically healthy with normal-weight (MHNW), MHO, metabolically unhealthy with normal-weight (MUNW), and metabolically unhealthy overweight/obesity (MUO) phenotypes was 38.76, 7.11, 38.67 and 15.47%, respectively. The results of logistic regression analysis showed that the MHO was associated with the z scores of hs-CRP in Chinese children and adolescents (OR=0.57, 95% CI: 0.39-0.83). Meanwhile, multivariate adjusted regression analysis showed that the relationship between hs-CRP and MHO among the overweight/obese was consistent with the results above, but among the normal-weight, only the highest quartile of TNF-α could increase the risk of MUNW (OR=1.65, 95% CI: 1.09-2.52). CONCLUSIONS: MHO phenotypes were not common in Chinese children and adolescents. Individuals with MHO had a more beneficial hs-CRP profile than those with MUO.
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Proteína C-Reativa/análise , Interleucina-6/sangue , Obesidade Metabolicamente Benigna/metabolismo , Sobrepeso/metabolismo , Obesidade Infantil/metabolismo , Fator de Necrose Tumoral alfa/sangue , Adolescente , Biomarcadores , Criança , Estudos Transversais , Feminino , Humanos , Modelos Logísticos , Masculino , FenótipoRESUMO
Background: Small cell lung cancer (SCLC) is an aggressive malignancy. Surgical resection is currently only recommended for clinical stage I patients who have been carefully staged. The clinical outcomes of patients with resected SCLCs vary because the disease is highly heterogeneous, suggesting that selected patients could be considered for surgical resection depending on their clinical and/or molecular characteristics. Methods: We collected data on a retrospective cohort of 119 limited-stage SCLC patients who underwent lobectomy with mediastinal lymph node dissection from March 2013 to March 2020 at Harbin Medical University Cancer Hospital. Correlations were derived using Fisher's exact test. Models of 2-year and 3-year survival were evaluated by deriving the area under receiver operating characteristic curves. Kaplan-Meier and Cox regression analyses were used to evaluate significant differences between the survival curves and hazard ratios. Results: The median disease-free survival (DFS) was 35.9 months (range 0.9-105.3 months), and the median overall survival (OS) was 45.2 months (range 4.8-105.3 months). Univariate analysis showed that TNM stage was significantly correlated with DFS and OS. The 2-year disease-free rates of patients with stage I, II, and III disease were 76.4%, 50.5%, and 36.1%, respectively, and the 3-year OS rates were 75.9%, 57.7%, and 34.4%, respectively. In pN + patients, multiple (or multiple-station) lymph node involvement significantly increased recurrence and reduced survival compared with patients with single or single-station metastases. Patients with peripheral SCLCs evidenced significantly better DFS and OS than did patients with central tumors. Multivariate analysis showed that TNM stage and tumor location were independently prognostic in Chinese patients with resected limited-stage SCLC. A combination of TNM stage and tumor location was helpful for prognosis. Conclusions: TNM stage and tumor location were independently prognostic in Chinese patients with resected SCLCs. Patient stratification by tumor location should inform the therapeutic strategy. The role of surgical resection for limited-stage SCLC patients must be reevaluated, as this may be appropriate for some patients.
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Neoplasias Pulmonares , Carcinoma de Pequenas Células do Pulmão , Humanos , Carcinoma de Pequenas Células do Pulmão/cirurgia , Carcinoma de Pequenas Células do Pulmão/patologia , Estudos Retrospectivos , Prognóstico , Linfonodos/patologia , Neoplasias Pulmonares/cirurgia , Neoplasias Pulmonares/patologia , Estadiamento de NeoplasiasRESUMO
PURPOSE: The predictive capacity between children's lipid accumulation product (CLAP) combining visceral adiposity index (VAI), CLAP, and VAI with metabolically unhealthy phenotype remained unclear. This study aimed to compare the ability of CLAP combining VAI, CLAP, VAI and traditional adiposity indicators (body mass index (BMI), waist circumference (WC), waist-to-height ratio (WHtR) and waist-to-hip ratio (WHR)) to predict metabolically unhealthy phenotype among Chinese children and adolescents. PATIENTS AND METHODS: In the cross-sectional study, 1714 children and adolescents aged 12 to 18 were selected by random cluster sampling, underwent a questionnaire survey, physical examination, biochemical tests and body composition was measured by bioelectrical impedance analysis (BIA). Participants were divided into four phenotypes according to BMI and metabolic syndrome components. The logarithmic CLAP (LnCLAP), VAI, BMI, WC, WHtR and WHR were standardized for sex and age using the z-score method (standardized variables: LnCLAP-z, VAI-z, BMI-z, WC-z, WHtR-z and WHR-z). RESULTS: LnCLAP-z ≥ 1, VAI-z ≥ 1, WC-z ≥ 1, and WHR-z ≥ 1 increased the risk of metabolically unhealthy normal-weight phenotype (the OR and 95% CI were 4.18 (1.75-10.02), 24.05 (12.79-45.21), 6.17 (1.14-33.51), 2.69 (1.07-6.72), respectively), LnCLAP-z ≥ 1, VAI-z ≥ 1 and WC-z ≥ 1 increased the risk of metabolically unhealthy overweight or obese phenotype (the OR and 95% CI were 2.67 (1.40-5.09), 10.30 (3.03-35.03), 2.19 (1.18-4.09), respectively). The area under the ROC curve (AUC) for CLAP combining VAI in the prediction of the metabolically unhealthy phenotype were 0.837 (0.776-0.899) and 0.876 (0.834-0.918) for boys and girls with normal-weight, 0.853 (0.803-0.903) and 0.794 (0.711-0.878) for boys and girls with overweight and obese (all P < 0.001), which were higher than CLAP, VAI, BMI, WC, WHtR and WHR. CONCLUSION: Among Chinese children and adolescents, CLAP combining VAI was a more effective indicator than CLAP, VAI and traditional adiposity indicators in predicting unhealthy metabolic phenotype.
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The relationship between visceral adiposity index (VAI) and unhealthy metabolic phenotype remained unclear in children and adolescents. This study aimed to investigate their association and compared the ability of VAI and traditional adiposity indicators (body mass index, waist circumference and waist-to-height ratio) to predict metabolically unhealthy phenotype among normal-weight, overweight and obese children and adolescents. In this cross-sectional study, 1722 children and adolescents aged 12-18 years were selected by cluster random sampling, underwent a questionnaire survey, physical examination and biochemical tests. Participants were divided into four phenotypes according to the combination of the weight status determined by body mass index (BMI) and metabolic syndrome components. Receiver operating characteristic (ROC) analysis and multivariate logistic regression were used to compare the predictive capacity between VAI and traditional adiposity indicators and their relationship with metabolically unhealthy phenotype. We found that VAI had better performance in predicting metabolically unhealthy phenotype than traditional adiposity indicators, the area under the receiver-operating characteristic curve (AUC) were 0.808 and 0.763 for boys and girls with normal-weight, 0.829 and 0.816 for boys and girls with overweight and obese (all P < 0.001). VAI was most strongly related to metabolically unhealthy phenotype whether or not to adjust the age, the adjusted OR and 95%CI was 6.15 (4.13-9.14) in boys with normal weight, and 5.90 (3.06-11.36), 4.95 (2.35-10.41) in boys and girls with overweight and obese, respectively (all P < 0.001). Our findings suggested VAI could be used as a comprehensive predictor to identify unhealthy metabolic phenotype in children and adolescents.