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Four-and-a-half LIM domains protein 2 (FHL2) is an adaptor protein that may interact with hypoxia inducible factor 1α (HIF-1α) or ß-catenin, two pivotal protective signaling in acute kidney injury (AKI). However, little is known about the regulation and function of FHL2 during AKI. We found that FHL2 was induced in renal tubular cells in patients with acute tubular necrosis and mice model of ischemia-reperfusion injury (IRI). In cultured renal proximal tubular cells (PTCs), hypoxia induced FHL2 expression and promoted the binding of HIF-1 to FHL2 promoter. Compared with control littermates, mice with PTC-specific deletion of FHL2 gene displayed worse renal function, more severe morphologic lesion, more tubular cell death and less cell proliferation, accompanying by downregulation of AQP1 and Na, K-ATPase after IRI. Consistently, loss of FHL2 in PTCs restricted activation of HIF-1 and ß-catenin signaling simultaneously, leading to attenuation of glycolysis, upregulation of apoptosis-related proteins and downregulation of proliferation-related proteins during IRI. In vitro, knockdown of FHL2 suppressed hypoxia-induced activation of HIF-1α and ß-catenin signaling pathways. Overexpression of FHL2 induced physical interactions between FHL2 and HIF-1α, ß-catenin, GSK-3ß or p300, and the combination of these interactions favored the stabilization and nuclear translocation of HIF-1α and ß-catenin, enhancing their mediated gene transcription. Collectively, these findings identify FHL2 as a direct downstream target gene of HIF-1 signaling and demonstrate that FHL2 could play a critical role in protecting against ischemic AKI by promoting the activation of HIF-1 and ß-catenin signaling through the interactions with its multiple protein partners.
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Injúria Renal Aguda , Túbulos Renais Proximais , Proteínas com Homeodomínio LIM , Proteínas Musculares , Traumatismo por Reperfusão , Fatores de Transcrição , beta Catenina , Animais , Proteínas com Homeodomínio LIM/metabolismo , Proteínas com Homeodomínio LIM/genética , Proteínas Musculares/metabolismo , Proteínas Musculares/genética , Injúria Renal Aguda/metabolismo , Injúria Renal Aguda/patologia , Injúria Renal Aguda/genética , Humanos , Túbulos Renais Proximais/metabolismo , Túbulos Renais Proximais/patologia , Traumatismo por Reperfusão/metabolismo , Traumatismo por Reperfusão/patologia , Traumatismo por Reperfusão/genética , Camundongos , beta Catenina/metabolismo , Fatores de Transcrição/metabolismo , Fatores de Transcrição/genética , Masculino , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Transdução de Sinais , Camundongos Endogâmicos C57BL , Camundongos Knockout , Glicogênio Sintase Quinase 3 beta/metabolismo , Glicogênio Sintase Quinase 3 beta/genética , Proliferação de Células , ApoptoseRESUMO
STUDY QUESTION: Do prepregnancy peripheral leukocytes (PPLs) and their subsets influence the risk of spontaneous abortion (SAB)? SUMMARY ANSWER: PPLs and their subsets are associated with the risk of SAB. WHAT IS KNOWN ALREADY: Compelling studies have revealed the crucial role of maternal peripheral leukocytes in embryo implantation and pregnancy maintenance. Adaptive changes are made by PPLs and their subsets after conception. STUDY DESIGN, SIZE, DURATION: This population-based retrospective cohort study was based on data from the National Free Pre-pregnancy Check-up Project (NFPCP) in mainland China. Couples preparing for pregnancy within the next six months were provided with free prepregnancy health examinations and counseling services for reproductive health. The current study was based on 1 310 494 female NFPCP participants aged 20-49 who became pregnant in 2016. After sequentially excluding 235 456 participants lost to follow-up, with multiple births, and who failed to complete blood tests, a total of 1 075 038 participants were included in the primary analysis. PARTICIPANTS/MATERIALS, SETTING, METHODS: PPLs and their subset counts and ratios were measured. The main outcome was SAB. A multivariable logistic regression model was used to estimate the odds ratio (OR) and 95% CI of SAB associated with PPLs and their subsets, and restricted cubic spline (RCS) was used to estimate the nonlinear exposure-response relationship. MAIN RESULTS AND ROLE OF CHANCE: Of the included pregnant participants, a total of 35 529 SAB events (3.30%) were recorded. Compared to participants with reference values of PPLs, the ORs (95% CIs) of leukopenia and leukocytosis for SAB were 1.14 (1.09-1.20) and 0.74 (0.69-0.79), respectively. The RCS result revealed a monotonous decreasing trend (Pnonlinear < 0.05). Similar relationships were observed for the neutrophil count and ratio, monocyte count, and middle-sized cell count and ratio. The lymphocyte ratio showed a positive and nonlinear relationship with the risk of SAB (Pnonlinear < 0.05). Both eosinophils and basophils showed positive relationships with the risk of SAB (eosinophil Pnonlinear > 0.05 and basophil Pnonlinear < 0.05). LIMITATIONS, REASONS FOR CAUTION: Chemical abortion events and the cause of SAB were not collected at follow-up. Whether women with abnormal PPLs had recovered during periconception was not determined. WIDER IMPLICATIONS OF THE FINDINGS: PPLs and their subsets are associated with the risk of SAB. Leukopenia and neutropenia screening in women preparing for pregnancy and developing a feasible PPL stimulation approach should be emphasized to utilize the immune window of opportunity to prevent SAB. STUDY FUNDING/COMPETING INTEREST(S): This study was approved by the Institutional Research Review Board of the National Health and Family Planning Commission. This study was supported by the National Key Research and Development Program of China (grants 2021YFC2700705 [Y.Y.] and 2016YFC100307 [X.M.]) and the National Natural Science Foundation of China (grant no. 82003472 [L.W.]). The funding source was not involved in the study design, data collection, analysis and interpretation of the data, writing the report, or the decision to submit this article for publication. No competing interests. TRIAL REGISTRATION NUMBER: N/A.
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Aborto Induzido , Aborto Espontâneo , Leucopenia , Gravidez , Animais , Feminino , Humanos , Cavalos , Aborto Espontâneo/etiologia , Estudos Retrospectivos , Aborto Induzido/efeitos adversos , Leucócitos , Leucopenia/complicaçõesRESUMO
BACKGROUND: Hepatic proteins, including albumin, prealbumin, and transferrin have been confirmed to be prognostic predictors in various cancers. This study aimed to comprehensively assess the prognostic value of these three serum markers in patients with cancer cachexia. METHODS: This multicenter prospective cohort study included 1303 cancer cachexia patients, among whom 592 deaths occurred during a median follow-up of 20.23 months. The definition of cachexia was based on the 2011 international consensus. Concordance index (C-index) and receiver operating characteristic (ROC) curves were applied to compare the prognostic performance. The primary outcome was overall survival, which was calculated using the Kaplan-Meier method generated by log-rank test. A Cox proportional hazard regression model was used to identify independent predictors associated with survival. The secondary outcomes included 90-days mortality and quality of life (QoL). RESULTS: C-index and ROC curves showed that albumin had the most accurate predictive capacity for survival, followed by transferrin and prealbumin. Multivariate Cox analysis confirmed that low albumin (hazard ratio [HR] = 1.51, 95% confidence interval [95%CI] = 1.28-1.80, P < 0.001), prealbumin (HR = 1.42, 95%CI = 1.19-1.69, P < 0.001), and transferrin (HR = 1.50, 95%CI = 1.25-1.80, P < 0.001) were independent risk factors for long-term survival in cancer patients with cachexia. In subgroup analysis, the prognostic value of low albumin was significant in patients with upper gastrointestinal, hepatobiliary and pancreatic, and colorectal cancers; low prealbumin was significant in colorectal cancer; and low transferrin was significant in patients with upper gastrointestinal and colorectal cancer. All three hepatic proteins were valuable as prognostic predictors for patients with advanced (Stage III and IV) cancer with cachexia. The risks of 90-days mortality and impaired QoL were higher in cachexia patients with low albumin, prealbumin, and transferrin levels. CONCLUSION: Low albumin, prealbumin, and transferrin levels were all independent prognostic factors affecting patients with cancer cachexia, especially in patients in the advanced stages. These results highlight the value of routinely checking serum hepatic proteins in clinical practice to predict the prognosis of patients with cancer cachexia.
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Neoplasias Colorretais , Pré-Albumina , Humanos , Qualidade de Vida , Caquexia/diagnóstico , Caquexia/etiologia , Estudos Prospectivos , Prognóstico , Albuminas , Proteínas Sanguíneas , Estudos de Coortes , TransferrinasRESUMO
OBJECTIVE: To investigate the association between sarcopenia, short-term efficacy, and long-term survival in patients with extensive small-cell lung cancer (SCLC) treated with standard first-line immunochemotherapy. METHODS: A total of 63 patients initially diagnosed with extensive-stage small cell lung cancer were enrolled in the prospective study from December 1, 2020 to December 31, 2022. The clinical characteristics, body composition, blood test results, and image data were obtained before treatment. Patients were divided into sarcopenia and non-sarcopenia groups according to the diagnostic criteria of the Asian Sarcopenia Working Group 2019. The primary outcome was overall survival (OS) and comprehensive survival analyses were performed. Secondary outcomes included short-term efficacy and adverse events associated with first-line immunochemotherapy. RESULTS: The median age of the 63 patients enrolled in our study was 63.0 years (40-80 years). The incidence of sarcopenia was 19.0% (12/63) in patients with extensive SCLC. Compared with non-sarcopenia patients, extensive-stage SCLC patients with sarcopenia were significantly older (69.0 vs. 62.0, P = 0.017), and had lower body mass index (BMI) (20.29 vs. 24.27, P < 0.001), hand grip strength (HGS) (20.42 vs. 30.75, P < 0.001), and albumin (35.9 vs. 41.40, P < 0.001). The objective response rate after two cycles of standard first-line immunochemotherapy in the sarcopenia group was lower than in the non-sarcopenia group (30.0 vs. 78.9%, P = 0.012). There was no significant difference in chemotherapy-related hematological toxicity between the two groups. During a median follow-up of 15 months (3-33 months), patients with extensive SCLC had a median OS of 24 months, with 1-year survival of 75% and 2-year survival of 52%, respectively. Compared to non-sarcopenia patients, the median OS in the sarcopenia group was significantly shorter (9 vs. 24 months, P = 0.0014). Multivariate Cox analysis showed that sarcopenia was an independent risk factor for OS in patients with extensive SCLC (HR = 4.993, 95%CI = 1.106-22.538, P = 0.037). CONCLUSIONS: Patients with Extensive SCLC and sarcopenia had worse clinical outcomes and shorter OS. Sarcopenia is a prognostic factor affecting first-line treatment efficacy and long-term survival of patients with SCLC in the era of immunotherapy.
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The formation of an asymmetric junction is key to graphene-based photodetectors of high-sensitive photodetectability, because such a junction can not only facilitate the diffusion or drift of photogenerated carriers but also realize a self-powered operation. Here, a monolayer-multilayer graphene junction photodetector is accomplished by selectively thinning part of a multilayer graphene to a high-quality monolayer. Benefiting from the large photoabsorption cross section of multilayer graphene and strong asymmetry caused by the significant differences in optoelectronic properties between monolayer and multilayer graphene, the monolayer-multilayer graphene junction shows a 7-fold increase in short-circuit photocurrent as compared with that at the monolayer graphene-metal contact in scanning photocurrent images. The asymmetric configuration also enables the photodetector to work at zero bias with minimized dark current noise and stand-by power consumption. Under global illumination with visible light, a photoswitching ratio of 3.4 × 103, a responsivity of 8.8 mA W-1, a specific detectivity of 1.3 × 108Jones and a response time of 11 ns can be obtained, suggesting a promising photoresponse. Moreover, it is worth mentioning that such a performance enhancement is achieved without compromising the broadband spectral response of graphene photodetector and it is hence applicable for long wavelength spectral range including infrared and terahertz.
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OBJECTIVE: The aim of this study was to investigate the association between autoinducer-2 (AI-2) of oral microbial flora and the alveolar bone destruction in periodontitis to determine if AI-2 may have the potential that monitor periodontitis and predict bone loss. BACKGROUND: Plaque biofilm was the initiating factor of periodontitis and the essential factor of periodontal tissue destruction. The formation of biofilms depended on the complex regulation of the quorum sensing (QS) system, in which bacteria could sense changes in surrounding bacterial density by secreting the autoinducer (AI) to regulate the corresponding physiological function. Most oral bacteria also communicated with each other to form biofilms administrating the QS system, which implied that the QS system of periodontal pathogens was related to periodontitis, but the specific relationship was unknown. METHOD: We collected the gingival crevicular fluid (GCF) samples and measured the concentration of AI-2 in samples using the Vibrio harveyi BB180 bioluminescent-reporter system. To explore the interaction between AI-2 and bone metabolism, we utilized AI-2 purified from Fusobacterium nucleatum to investigate the impact of F. nucleatum AI-2 on osteoclast differentiation. Moreover, we constructed murine periodontitis models and multi-species biofilm models to study the association between AI-2 and periodontal disease progression. RESULTS: The AI-2 concentration in GCF samples increased along with periodontal disease progression (p < .0001). F. nucleatum AI-2 promoted osteoclast differentiation in a dose-dependent manner. In the periodontitis mice model, the CEJ-ABC distance in the F. nucleatum AI-2 treatment group was higher than that in the simple ligation group (p < .01), and the maxilla of the mice in the group exhibited significantly lower BMD and BV/TV values (p < .05). CONCLUSIONS: We demonstrated that the AI-2 concentration varied with the alveolar bone destruction in periodontitis, and it may have the potential for screening periodontitis. F. nucleatum AI-2 promoted osteoclast differentiation in a dose-dependent manner and aggravated bone loss.
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Perda do Osso Alveolar , Biofilmes , Fusobacterium nucleatum , Homosserina , Lactonas , Periodontite , Perda do Osso Alveolar/microbiologia , Perda do Osso Alveolar/metabolismo , Periodontite/microbiologia , Animais , Homosserina/análogos & derivados , Homosserina/metabolismo , Biofilmes/crescimento & desenvolvimento , Camundongos , Humanos , Líquido do Sulco Gengival/microbiologia , Líquido do Sulco Gengival/química , Masculino , Modelos Animais de Doenças , Osteoclastos , Percepção de Quorum , Feminino , Adulto , Diferenciação Celular , Pessoa de Meia-Idade , Microtomografia por Raio-XRESUMO
BACKGROUND: The International IgA Nephropathy (IgAN) Network developed and validated two prognostic prediction models for IgAN, one incorporating a race parameter. These models could anticipate the risk of a 50% reduction in estimated glomerular filtration rate (eGFR) or progression to end-stage renal disease (ESRD) subsequent to an IgAN diagnosis via renal biopsy. This investigation aimed to validate the International IgA Nephropathy Prediction Tool (IIgANPT) within a contemporary Chinese cohort. METHODS: Within this study,185 patients diagnosed with IgAN via renal biopsy at the Center for Kidney Disease, Second Affiliated Hospital of Nanjing Medical University, between January 2012 and December 2021, were encompassed. Each patient's risk of progression was assessed utilizing the IIgANPT formula. The primary outcome, a 50% decline in eGFR or progression to ESRD, was examined. Two predictive models, one inclusive and the other exclusive of a race parameter, underwent evaluation via receiver-operating characteristic (ROC) curves, subgroup survival analyses, calibration plots, and decision curve analyses. RESULTS: The median follow-up duration within our cohort spanned 5.1 years, during which 18 patients encountered the primary outcome. The subgroup survival curves exhibited distinct separations, and the comparison of clinical and histological characteristics among the risk subgroups revealed significant differences. Both models demonstrated outstanding discrimination, evidenced by the areas under the ROC curve at five years: 0.882 and 0.878. Whether incorporating the race parameter or not, both prediction models exhibited acceptable calibration. Decision curve analysis affirmed the favorable clinical utility of both models. CONCLUSIONS: Both prognostic risk evaluation models for IgAN exhibited remarkable discrimination, sound calibration, and acceptable clinical utility.
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Glomerulonefrite por IGA , Falência Renal Crônica , Humanos , Glomerulonefrite por IGA/diagnóstico , Glomerulonefrite por IGA/patologia , Prognóstico , Falência Renal Crônica/diagnóstico , Falência Renal Crônica/etiologia , Análise de Sobrevida , Taxa de Filtração Glomerular , Progressão da Doença , Estudos RetrospectivosRESUMO
BACKGROUND: Accurately identifying patients with axillary pathologic complete response (pCR) after neoadjuvant chemotherapy (NAC) in breast cancer patients remains challenging. PURPOSE: To compare the feasibility of shear wave elastography (SWE) performed on breast tumors and axillary lymph nodes (LNs) in predicting the axillary status after NAC. MATERIALS AND METHODS: This prospective study included a total of 319 breast cancer patients with biopsy-proven positive node who received NAC followed by axillary lymph node dissection from 2019 to 2022. The correlations between shear wave velocity (SWV) and pathologic characteristics were analyzed separately for both breast tumors and LNs after NAC. We compared the performance of SWV between breast tumors and LNs in predicting the axillary status after NAC. Additionally, we evaluated the performance of the most significantly correlated pathologic characteristic in breast tumors and LNs to investigate the pathologic evidence supporting the use of breast or axilla SWE. RESULTS: Axillary pCR was achieved in 51.41% of patients with node-positive breast cancer. In breast tumors, there is a stronger correlation between SWV and collagen volume fraction (CVF) (r = 0.52, p < 0.001) compared to tumor cell density (TCD) (r = 0.37, p < 0.001). In axillary LNs, SWV was weakly correlated with CVF (r = 0.31, p = 0.177) and TCD (r = 0.29, p = 0.213). No significant correlation was found between SWV and necrosis proportion in breast tumors or axillary LNs. The predictive performances of both SWV and CVF for axillary pCR were found to be superior in breast tumors (AUC = 0.87 and 0.85, respectively) compared to axillary LNs (AUC = 0.70 and 0.74, respectively). CONCLUSION: SWE has the ability to characterize the extracellular matrix, and serves as a promising modality for evaluating axillary LNs after NAC. Notably, breast SWE outperform axilla SWE in determining the axillary status in breast cancer patients after NAC.
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Axila , Neoplasias da Mama , Técnicas de Imagem por Elasticidade , Linfonodos , Metástase Linfática , Terapia Neoadjuvante , Humanos , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/patologia , Feminino , Técnicas de Imagem por Elasticidade/métodos , Pessoa de Meia-Idade , Estudos Prospectivos , Adulto , Linfonodos/diagnóstico por imagem , Linfonodos/patologia , Metástase Linfática/diagnóstico por imagem , Idoso , Estudos de Viabilidade , Excisão de Linfonodo , Quimioterapia AdjuvanteRESUMO
Sepsis usually leads to lethal multiorgan dysfunction including acute liver failure (ALF) and acute lung injury (ALI). This research sought to reveal the lipid alteration of anti-high mobility group box 1 (HMGB1) treatment in sepsis-induced ALF and ALI by lipidomics. The cecal ligation and puncture-induced mouse model was established and the anti-HMGB1 neutralizing antibody was administrated. The histopathological characteristics and inflammatory factors were determined to assess the efficacy of the antibody. Utraperformance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry was used to determine lipid metabolism profiles in the liver and lung. The underlying biomarkers were identified through multivariate statistical analysis and correlation analysis with traditional physiological indicators. The pathological and biochemical results demonstrated that anti-HMGB1 neutralizing antibodies mitigated ALF and ALI in mice. Three differential metabolites in the liver and six various metabolites in the lung were significantly reversed by anti-HMGB1 treatment, mainly involved in arachidonic acid metabolism, glycerophospholipid metabolism, and sphingolipid metabolism. Additionally, we investigated several traditional signaling pathways associated with HMGB1. However, the correlation between these traditional pathways and anti-HMGB1 intervention was not significant in the current study. In conclusion, our finding provided some scientific basis for targeting HMGB1 in sepsis-induced liver and lung injury. Mass spectrometry data with identifier no. MTBLS6466 have been uploaded to MetaboLights (http://www.ebi.ac.uk/metabolights/login).
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Lesão Pulmonar Aguda , Falência Hepática Aguda , Sepse , Camundongos , Animais , Lipidômica , Lesão Pulmonar Aguda/etiologia , Pulmão/metabolismo , Anticorpos Neutralizantes , Falência Hepática Aguda/patologia , Sepse/complicações , Sepse/patologia , Modelos Animais de DoençasRESUMO
We report herein the synthesis of exo-chalcogenated methylene chroman-3-ones via palladium-catalyzed intramolecular acyl-chalcogenation of alkyne with thio- and selenoesters. Chalcogen containing tetrasubstituted alkenes are obtained stereoselectively. This protocol tolerates various functional groups and heterocycles, affording the chroman-3-one products in moderate-to-good yields.
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Nitrate-to-ammonia electrochemical conversion is important for decreasing water pollution and increasing the production of valuable ammonia. However, achieving high ammonium production without undesirable byproducts is difficult. Cu-doped MIL-88-derived bimetallic oxide catalysts with electrocatalytically active Fe-O-Cu bridges, which have high NO3- adsorption energy and facilitate N-intermediate hydrogenation, are developed for NH4+ production. Cu doping promotes hybridization between the O 2p of NO3- and Fe-Cu 3d, facilitating the adsorption and reduction of NO3- with a low Tafel slope (62.1 mV dec-1) and high ammonia yield (1698.8 µg·h-1·cm-2). The cathode efficiency is stable for seven cycles. Cu adjacent to Fe sites inhibits hydrogen evolution, promotes NO3- adsorption, and decreases the intermediate adsorption energy barrier. This study provides new opportunities for fabricating diverse binary metal oxides with new interfaces as efficient cathode materials for selective electroreduction.
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Amônia , Nitratos , Domínio Catalítico , Adsorção , ÓxidosRESUMO
PURPOSE: Our study aimed to comprehensively analyze the association between anemia and systemic inflammation in older patients with cancer. METHODS: This multicenter prospective cohort study included 4955 older patients with cancer between 2013 and 2020. Logistic regression analysis was performed to investigate risk factors of anemia, reporting odds ratios (ORs), and 95% confidence intervals (CIs). Comprehensive survival analyses, including Kaplan-Meier curve, Cox proportional risk model, and subgroup analysis, were performed. RESULTS: The participants' median age was 70.0 (interquartile range [IQR]=67.0-74.0) years, with 3293 (66.5%) males and 1662 (33.5%) females. There were 1717 (34.7%) older patients with cancer diagnosed with anemia. High neutrophil-to-lymphocyte ratio (NLR) was an independent risk factor associated with anemia (adjusted OR=1.97, 95%CI=1.73-2.24, P<0.001). In older patients with cancer and different anemia levels, the median overall survival was significantly shorter in those with a high NLR. In multivariate Cox analysis, high NLR served as a negative factor, independently affecting survival. The anemia-inflammation prognostic grading system showed a significant survival discriminative performance in older patients with cancer. After adjusting for confounders, high grades were independent risk factors for survival (grade 2: hazard ratio [HR] = 1.38, 95%CI = 1.26-1.52, P<0.001; grade 3: HR=1.82 95%CI = 1.59-2.09, P<0.001). This grading system was beneficial in determining survival in patients with lung, digestive tract, and urogenital cancers. CONCLUSIONS: Increased systemic inflammation is an independent risk factor for anemia. A high inflammatory status is also associated with poor survival in older cancer patients at different anemia levels. The anemia-inflammation grading system is beneficial for determining the prognosis in older patients with cancer.
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Inflamação , Neoplasias , Masculino , Feminino , Humanos , Idoso , Estudos Prospectivos , Inflamação/epidemiologia , Inflamação/diagnóstico , Prognóstico , Neoplasias/complicações , Neoplasias/epidemiologia , Linfócitos , Neutrófilos , Estudos RetrospectivosRESUMO
OBJECTIVES: This study aimed to construct a formula to predict L3 skeletal muscle cross-sectional area (CSA) from C3 CSA and to select the cutoff values to evaluate the nutritional status in OSCC. MATERIALS AND METHODS: A total of 220 OSCC patients in Nanfang Hospital were divided into two groups: the training set (n = 100) and the validation set (n = 120). Patients in the training set were performed the preoperative whole-body positron emission tomography-computed tomography (PET/CT) scans, and patients in the validation set received preoperative head-and-neck computed tomography (CT) scans. C3 CSA and L3 CSA were delineated. The predictive formula was established, and the gender-specific thresholds of malnutrition were obtained by X-tile software in training set. Finally, the formula and cutoff values were validated. RESULTS: The predictive formula was successfully established. The gender-specific cutoff values for L3 SMI were 55.0 cm2 /m2 for men and 36.6 cm2 /m2 for women. There were no differences between the overall survival (OS) of patients diagnosed with malnutrition and that of patients who are not malnutrition. CONCLUSIONS: Our studies reveal that the L3 CSA could be calculated by C3 CSA conveniently with our formula in OSCC, which allowed us to assess malnutrition with head-and-neck CT image. However, there is no direct connection found between malnutrition and OS in OSCC. Hence, further studies with a larger sample size may be required.
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Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Desnutrição , Neoplasias Bucais , Sarcopenia , Masculino , Humanos , Feminino , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Carcinoma de Células Escamosas/complicações , Carcinoma de Células Escamosas/diagnóstico por imagem , Carcinoma de Células Escamosas/patologia , Sarcopenia/diagnóstico , Sarcopenia/patologia , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Neoplasias Bucais/complicações , Neoplasias Bucais/diagnóstico por imagem , Neoplasias Bucais/patologia , Músculo Esquelético/diagnóstico por imagem , Músculo Esquelético/patologia , Prognóstico , Desnutrição/etiologia , Neoplasias de Cabeça e Pescoço/complicações , Neoplasias de Cabeça e Pescoço/diagnóstico por imagem , Neoplasias de Cabeça e Pescoço/patologia , Estudos RetrospectivosRESUMO
BACKGROUND: The postponement of parenthood is a global public health issue that has received attention of many public health experts. However, few studies have investigated the postponement in marriage age, marriage and conception interval, and pregnancy age in terms of demographic and regional heterogenicities. METHODS: This is a cross-sectional, registry-based study, and a total of 13 894 601 nulliparous couples who participated in the National Free Pre-Pregnancy Check-ups Project and became pregnant during 2013-2019 were included. We calculated annual percentage change and forest plots for marriage age, marriage and conception interval, and pregnancy age. RESULTS: Late marriage (marriage age ≥ 35 years), long marriage and conception interval (marriage and conception interval ≥ 2 years), and advanced pregnancy (pregnancy age ≥ 35 years) increased from 1.20%, 22.01%, and 1.88% in 2013 to 1.69%, 32.75%, and 2.79% in 2019, respectively. The corresponding annual percentage changes were 6.55%, 8.44%, and 8.17%. Participants without higher education had a higher annual percentage change, but comparable prevalence for long marriage and conception interval with participants with higher education. Participants residing in second- or new first-tier cities, and the northeast of China who had a higher prevalence of parenthood postponement also had higher corresponding annual percentage changes. CONCLUSIONS: Structural postponement of parenthood with demographic and regional heterogenicities was observed among Chinese nulliparous couples with planned pregnancies during 2013-2019. Inclusive and comprehensive parenting support should be developed and implemented in mainland China to minimize the negative health effects arising from the postponement, especially for couples without higher education and living in new first/second-tier cities or the northeast China.
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População do Leste Asiático , Serviços de Planejamento Familiar , Adulto , Feminino , Humanos , Gravidez , Estudos Transversais , Países em Desenvolvimento , Casamento , Dinâmica Populacional , Poder FamiliarRESUMO
OBJECTIVES: To investigate the influence of different mucosal phenotypes on peri-implant marginal bone loss. MATERIALS AND METHODS: The search was conducted in five databases including PubMed, Embase, Cochrane, Scopus, and Web of Science (until 1st Sept. 2022) to identify relevant clinical studies. Potentially relevant journals were also manually searched. Two reviewers independently screened studies, extracted data, and evaluated the quality of the studies. Prospective clinical trials and observational studies investigating peri-implant marginal bone loss in thick-mucosa and thin-mucosa groups were included. RESULTS: A total of 14 studies were included in this systematic review. Results of the meta-analysis revealed a weighted mean difference of 0.38 mm for marginal bone loss between thick- and thin-mucosa groups (95% confidence interval = 0.02-0.74, P = 0.002). Statistical significance existed in short-term (follow-up ≤ 1 year) data (WMD = 0.41 mm, 95%CI = 0.11-0.70, P = 0.007), but not in long term (follow-up ≥ 3 y) data (WMD = 0.17 mm, 95%CI = - 0.02-0.36, P = 0.07). Survival rate revealed no difference between thick and thin mucosa groups. In subgroup analyses, a positive association between thick mucosa and less marginal bone loss was found in the non-submerged group, cement-retained group, and bone-level group. CONCLUSIONS: A significantly less marginal bone loss occurred in implants with thick mucosa than with thin mucosa in the short term, whereas no significant difference was observed in the long term. Due to the substantial heterogeneity and limited long-term data, further high-quality evidence is warranted to confirm the results. CLINICAL RELEVANCE: Clinicians are advised to use caution in treating patients with thin mucosa and adhere closely to indications and protocols to minimize marginal bone loss.
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Perda do Osso Alveolar , Implantes Dentários , Humanos , Implantes Dentários/efeitos adversos , Implantação Dentária Endóssea/efeitos adversos , Estudos Prospectivos , Perda do Osso Alveolar/etiologia , MucosaRESUMO
Neuregulin 4 (NRG4) is an important adipocytokine, which plays crucial roles in maintaining energy balance, regulating glucose and lipid metabolism, and preventing non-alcoholic fatty liver disease in mammals. At present, the genomic organization, transcript and protein isoforms of human NRG4 gene have been fully explored. Previous studies in our laboratory have shown that the NRG4 gene is expressed in chicken adipose tissue, but the chicken NRG4 (cNRG4) genomic structure, transcript and protein isoforms are still unknown. To this end, in this study, the genomic and transcriptional structure of the cNRG4 gene were systematically investigated using rapid amplification of cDNA ends (RACE) and reverse transcription-polymerase chain reaction (RT-PCR). The results showed that the coding region (CDS) of the cNRG4 gene was small, but it had a very complex transcriptional structure characterized by multiple transcription start sites, alternative splicing, intron retention, cryptic exons, and alternative polyadenylation, thus leading to production of four 5?UTR isoforms (cNRG4 A, cNRG4 B, cNRG4 C, and cNRG4 D) and six 3?UTR isoforms (cNRG4 a, cNRG4 b, cNRG4 c, cNRG4 d, cNRG4 e, and cNRG4 f) of the cNRG4 gene. The cNRG4 gene spanned 21,969 bp of genomic DNA (Chr.10:3,490,314~3,512,282) and consisted of 11 exons and 10 introns. Compared with the cNRG4 gene mRNA sequence (NM_001030544.4), two novel exons and one cryptic exon of the cNRG4 gene were identified in this study. Bioinformatics analysis, RT-PCR, cloning and sequencing analysis showed that the cNRG4 gene could encode three protein isoforms (cNRG4-1, cNRG4-2 and cNRG4-3). This study lays a foundation for further research on the function and regulation of the cNRG4 gene.
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Processamento Alternativo , Galinhas , Animais , Processamento Alternativo/genética , Sequência de Bases , Galinhas/genética , DNA Complementar/genética , Genômica , Íntrons/genética , Neurregulinas/genética , Isoformas de Proteínas/genéticaRESUMO
ATP-dependent chromatin remodeling complexes regulate chromatin structure and play important roles in gene expression, differentiation, development and cancer progression. Dysregulation in the subunits of the complexes often has been found in different cancers, but how they influence cancer initiation and progression is not fully understood. Here, we show that Chromatin Accessibility Complex Subunit 1 (CHRAC1), the accessory subunit of chromatin remodeling complex, is highly expressed in lung cancer tissues, which correlates with poor prognosis in lung cancer patients. CHRAC1 overexpression promotes lung cancer cell proliferation and migration in vitro and tumor growth in genetically engineered KrasG12D.LSL lung adenocarcinoma mouse model. Consistent with this, CHRAC1 silencing inhibits cell proliferation and migration in lung cancer cells and suppresses tumor growth in xenograft mouse model. Further, CHRAC1 binds to the transcription coactivator Yes-associated protein (YAP), enhances the transcription of downstream target oncogenes in Hippo pathway and thus promotes the tumor growth. Together, our study defines a critical role of CHRAC1 in promoting YAP transcriptional activity and lung cancer tumorigenesis, which makes it a potential target for lung cancer.
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Adenocarcinoma de Pulmão , Neoplasias Pulmonares , Adenocarcinoma de Pulmão/genética , Animais , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Cromatina , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Humanos , Neoplasias Pulmonares/patologia , Camundongos , Nucleoproteínas/genética , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismoRESUMO
We present herein a novel strategy for the preparation of ketones from aldehydes and allylic boronic esters. This reaction involves the allylation of aldehydes with allylic boronic esters and the Rh-catalyzed chain-walking of homoallylic alcohols. The key to this successful development is the protodeboronation of alkenyl borylether intermediate via a tetravalent borate anion species in the presence of KHF2 and MeOH. This approach features mild reaction conditions, broad substrate scope, and excellent functional group tolerance. Mechanistic studies also supported that the tandem allylation and chain-walking process were involved.
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Aldeídos , Ródio , Catálise , Cetonas , EstereoisomerismoRESUMO
BACKGROUND: The aim of this study was to investigate the effect of coenzyme Q10 (CoQ10), a commonly used nutritional supplement, on intracranial aneurysm (IA) initiation and progression in a mouse model, as well as the mechanism. METHODS: Hydrogen peroxide (H2O2) was used to treat mouse-derived vascular smooth muscle cells (VSMCs) to induce oxidative injury, followed by incubation with CoQ10. In the mouse IA model established by elastase injection, CoQ10 was orally administered at 10 mg/kg every other day for 14 days, during which the incidence of IA, rupture rate, symptom-free survival, and systolic blood pressure were recorded. RESULTS: CoQ10 promoted the expression of nuclear factor erythroid 2-related factor 2 and antioxidant enzymes. In H2O2-treated VSMCs, reactive oxygen species and cell apoptosis were reduced by CoQ10. In IA mice, CoQ10 treatment decreased the rupture rate of IA, improved the symptom-free survival, and reduced systolic blood pressure. Macrophage infiltration and expression of pro-inflammatory cytokines in the cerebral arteries were mitigated by CoQ10 treatment. CONCLUSIONS: CoQ10 is effective in reducing oxidative stress in VSMCs, thereby attenuating IA formation and rupture in mice. CoQ10 also alleviates inflammation and restores normal phenotypes of VSMCs in the cerebral arteries. Our data suggest that CoQ10 is a potentially effective drug for managing IA. IMPACT: To investigate the effect of CoQ10, a commonly used nutritional supplement, on IA initiation and progression in a mouse model, as well as the mechanism. CoQ10 promoted the expression of Nrf2 and antioxidant enzymes. In H2O2-treated VSMCs, ROS and cell apoptosis were reduced by CoQ10. CoQ10 is effective in reducing oxidative stress in VSMCs, thereby attenuating IA formation and rupture in mice.
Assuntos
Antioxidantes , Aneurisma Intracraniano , Animais , Antioxidantes/metabolismo , Antioxidantes/farmacologia , Modelos Animais de Doenças , Peróxido de Hidrogênio/farmacologia , Aneurisma Intracraniano/tratamento farmacológico , Aneurisma Intracraniano/metabolismo , Camundongos , Estresse Oxidativo , Ubiquinona/análogos & derivados , Ubiquinona/metabolismo , Ubiquinona/farmacologiaRESUMO
OBJECTIVE: To determine the ability of conventional ultrasound (US) combined with shear wave elastography (SWE) to reveal axillary status after neoadjuvant chemotherapy (NAC) in breast cancer patients. METHODS: From September 2016 to December 2021, 201 patients with node-positive breast cancer who underwent NAC were enrolled in this prospective study. Conventional US features of axillary lymph nodes and SWE characteristics of breast lesions after NAC were analyzed. The diagnostic performances of US, SWE, and their combination were assessed using multivariate logistic regression and receiver operator characteristic curve (ROC) analyses. RESULTS: The area under the ROC curve (AUC) for the ability of conventional US features to determine axillary status after NAC was 0.82, with a sensitivity of 85.23%, a specificity of 67.39%, and an accuracy of 76.11%. Shear wave velocity (SWV) displayed moderate performance for predicting axilla status after NAC with SWVmean demonstrating an AUC of 0.85. Cortical thickness and shape of axillary nodes and SWVmean of breast tumors were independently associated with axillary nodal metastasis after NAC. Compared to conventional US, the combination of conventional US of axillary lymph nodes with SWE of breast lesions achieved a significantly higher AUC (0.90 vs 0.82, p < 0.01, Delong's test) with a sensitivity of 87.50%, improved specificity of 82.61% and accuracy of 85.00%. CONCLUSIONS: Breast SWE was independently associated with residual metastasis of axillary node after NAC in patients with initially diagnosed positive axilla. Combining SWE with conventional US showed good diagnostic performance for axillary node disease after NAC. KEY POINTS: ⢠Breast SWE can serve as a supplement to axilla US for the evaluation of the axilla after NAC. ⢠The combination of axilla US with breast SWE may be a promising method to facilitate less-invasive treatment in patients receiving NAC.