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1.
Nature ; 606(7915): 678-682, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35732764

RESUMO

A long-standing question in nuclear physics is whether chargeless nuclear systems can exist. To our knowledge, only neutron stars represent near-pure neutron systems, where neutrons are squeezed together by the gravitational force to very high densities. The experimental search for isolated multi-neutron systems has been an ongoing quest for several decades1, with a particular focus on the four-neutron system called the tetraneutron, resulting in only a few indications of its existence so far2-4, leaving the tetraneutron an elusive nuclear system for six decades. Here we report on the observation of a resonance-like structure near threshold in the four-neutron system that is consistent with a quasi-bound tetraneutron state existing for a very short time. The measured energy and width of this state provide a key benchmark for our understanding of the nuclear force. The use of an experimental approach based on a knockout reaction at large momentum transfer with a radioactive high-energy 8He beam was key.

2.
Ann Oncol ; 35(3): 302-307, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38092229

RESUMO

BACKGROUND: Primary analysis of the multicenter, open-label, single-arm, phase II DESTINY-Breast01 trial (median follow-up 11.1 months) demonstrated durable antitumor activity with trastuzumab deruxtecan (T-DXd) in patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (mBC) previously treated with trastuzumab emtansine (T-DM1). We report updated cumulative survival outcomes with a median follow-up of 26.5 months (data cut-off 26 March 2021). PATIENTS AND METHODS: Patients with HER2-positive mBC resistant or refractory to T-DM1 received T-DXd 5.4 mg/kg intravenously every 3 weeks until disease progression, unacceptable adverse events, or withdrawal of consent. The primary endpoint was confirmed objective response rate (ORR) by independent central review (ICR). Secondary endpoints included overall survival (OS), duration of response (DoR), progression-free survival (PFS), and safety. RESULTS: The ORR by ICR was 62.0% [95% confidence interval (CI) 54.5% to 69.0%] in patients who received T-DXd 5.4 mg/kg every 3 weeks (n = 184). Median OS was 29.1 months (95% CI 24.6-36.1 months). Median PFS and DoR were 19.4 months (95% CI 14.1-25.0 months) and 18.2 months (95% CI 15.0 months-not evaluable), respectively. Drug-related treatment-emergent adverse events (TEAEs) were observed in 183 patients (99.5%), and 99 patients (53.8%) had one or more grade ≥3 TEAEs. Adjudicated drug-related interstitial lung disease/pneumonitis occurred in 15.8% of patients (n = 29), of which 2.7% (n = 5) were grade 5. CONCLUSIONS: These updated results provide further evidence of sustained antitumor activity of T-DXd with a consistent safety profile in heavily pretreated patients with HER2-positive mBC.


Assuntos
Neoplasias da Mama , Camptotecina/análogos & derivados , Imunoconjugados , Humanos , Feminino , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Anticorpos Monoclonais Humanizados , Trastuzumab/efeitos adversos , Imunoconjugados/efeitos adversos , Ado-Trastuzumab Emtansina , Receptor ErbB-2/genética , Receptor ErbB-2/metabolismo
3.
Ann Oncol ; 35(2): 190-199, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37872020

RESUMO

BACKGROUND: Immune checkpoint inhibitors in combination with tyrosine kinase inhibitors are standard treatments for advanced clear cell renal cell carcinoma (RCC). This phase III RENOTORCH study compared the efficacy and safety of toripalimab plus axitinib versus sunitinib for the first-line treatment of patients with intermediate-/poor-risk advanced RCC. PATIENTS AND METHODS: Patients with intermediate-/poor-risk unresectable or metastatic RCC were randomized in a ratio of 1 : 1 to receive toripalimab (240 mg intravenously once every 3 weeks) plus axitinib (5 mg orally twice daily) or sunitinib [50 mg orally once daily for 4 weeks (6-week cycle) or 2 weeks (3-week cycle)]. The primary endpoint was progression-free survival (PFS) assessed by an independent review committee (IRC). The secondary endpoints were investigator-assessed PFS, overall response rate (ORR), overall survival (OS), and safety. RESULTS: A total of 421 patients were randomized to receive toripalimab plus axitinib (n = 210) or sunitinib (n = 211). With a median follow-up of 14.6 months, toripalimab plus axitinib significantly reduced the risk of disease progression or death by 35% compared with sunitinib as assessed by an IRC [hazard ratio (HR) 0.65, 95% confidence interval (CI) 0.49-0.86; P = 0.0028]. The median PFS was 18.0 months in the toripalimab-axitinib group, whereas it was 9.8 months in the sunitinib group. The IRC-assessed ORR was significantly higher in the toripalimab-axitinib group compared with the sunitinib group (56.7% versus 30.8%; P < 0.0001). An OS trend favoring toripalimab plus axitinib was also observed (HR 0.61, 95% CI 0.40-0.92). Treatment-related grade ≥3 adverse events occurred in 61.5% of patients in the toripalimab-axitinib group and 58.6% of patients in the sunitinib group. CONCLUSION: In patients with previously untreated intermediate-/poor-risk advanced RCC, toripalimab plus axitinib provided significantly longer PFS and higher ORR than sunitinib and had a manageable safety profile TRIAL REGISTRATION: ClinicalTrials.gov NCT04394975.


Assuntos
Anticorpos Monoclonais Humanizados , Carcinoma de Células Renais , Neoplasias Renais , Humanos , Anticorpos Monoclonais Humanizados/uso terapêutico , Axitinibe/uso terapêutico , Carcinoma de Células Renais/tratamento farmacológico , Carcinoma de Células Renais/patologia , Neoplasias Renais/tratamento farmacológico , Sunitinibe/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos
4.
Phys Rev Lett ; 132(17): 171001, 2024 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-38728703

RESUMO

Recently a dark matter-electron (DM-electron) paradigm has drawn much attention. Models beyond the standard halo model describing DM accelerated by high energy celestial bodies are under intense examination as well. In this Letter, a velocity components analysis (VCA) method dedicated to swift analysis of accelerated DM-electron interactions via semiconductor detectors is proposed and the first HPGe detector-based accelerated DM-electron analysis is realized. Utilizing the method, the first germanium based constraint on sub-GeV solar reflected DM-electron interaction is presented with the 205.4 kg·day dataset from the CDEX-10 experiment. In the heavy mediator scenario, our result excels in the mass range of 5-15 keV/c^{2}, achieving a 3 orders of magnitude improvement comparing with previous semiconductor experiments. In the light mediator scenario, the strongest laboratory constraint for DM lighter than 0.1 MeV/c^{2} is presented. The result proves the feasibility and demonstrates the vast potential of the VCA technique in future accelerated DM-electron analyses with semiconductor detectors.

5.
Phys Chem Chem Phys ; 26(20): 14930-14936, 2024 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-38738788

RESUMO

The unique 4f orbitals and abundant electronic energy levels of rare earth elements enable effective doping and modification to enhance hydrogen storage performance, making it an increasingly prominent focus of research. The structures of neutral and cationic CeHn0/+ (n = 2-20) clusters have been determined using the Crystal Structure AnaLYsis by Particle Swarm Optimization (CALYPSO) method in conjunction with density functional theory (DFT). Interestingly, the CeH13 and CeH14+ exhibit remarkable stability in the doublet state with Cs and C2v symmetry, respectively. The adsorption energy of CeHn0/+ (n = 2-20) suggests a preference for H atoms to chemically adsorb on Ce atoms. The analysis of molecular orbital composition reveals that the stability of both CeH13 and CeH14+ is attributed to the significant hybridization between the H 1s and Ce 4f orbitals. Both CeH13 and CeH14+ demonstrate significant hydrogen storage capacities, with values reaching 8.5 wt% and 9.1 wt%, respectively.

6.
Environ Res ; 241: 117010, 2024 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-37696323

RESUMO

BACKGROUND: Prior animal and epidemiological studies suggest that per- and polyfluoroalkyl substances (PFAS) exposure may be associated with reduced birth weight. However, results from prior studies evaluated a relatively small set of PFAS. OBJECTIVES: Determine associations of gestational PFAS concentrations in maternal serum samples banked for 60 years with birth outcomes. METHODS: We used data from 97 pregnant women from Boston and Providence that enrolled in the Collaborative Perinatal Project (CPP) study (1960-1966). We quantified concentrations of 27 PFAS in maternal serum in pregnancy and measured infant weight, height and ponderal index at birth. Covariate-adjusted associations between 11 PFAS concentrations (>75% detection limits) and birth outcomes were estimated using linear regression methods. RESULTS: Median concentrations of PFOA, PFNA, PFHxS, and PFOS were 6.189, 0.330, 14.432, and 38.170 ng/mL, respectively. We found that elevated PFAS concentrations during pregnancy were significantly associated with lower birth weight and ponderal index at birth, but no significant associations were found with birth length. Specifically, infants born to women with PFAS concentrations ≥ median levels had significantly lower birth weight (PFOS: ß = -0.323, P = 0.006; PFHxS: ß = -0.292, P = 0.015; PFOA: ß = -0.233, P = 0.03; PFHpS: ß = -0.239, P = 0.023; PFNA: ß = -0.239, P = 0.017). Similarly, women with PFAS concentrations ≥ median levels had significantly lower ponderal index (PFHxS: ß = -0.168, P = 0.020; PFHxA: ß = -0.148, P = 0.018). CONCLUSIONS: Using data from this US-based cohort study, we found that 1) maternal PFAS levels from the 1960s exceeded values in contemporaneous populations and 2) that gestational concentrations of certain PFAS were associated with lower birth weight and infant ponderal index. Additional studies with larger sample size are needed to further examine the associations of gestational exposure to individual PFAS and their mixtures with adverse birth outcomes.


Assuntos
Ácidos Alcanossulfônicos , Poluentes Ambientais , Fluorocarbonos , Complicações na Gravidez , Recém-Nascido , Lactente , Humanos , Feminino , Gravidez , Estudos de Coortes , Gestantes , Peso ao Nascer , Poluentes Ambientais/toxicidade , Fluorocarbonos/toxicidade , Complicações na Gravidez/induzido quimicamente
7.
Clin Radiol ; 2024 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-38866677

RESUMO

BACKGROUND: Gastro-tracheal fistula (GTF) is one of the most serious complications after esophagogastrostomy and radiotherapy, with very high disability and mortality rates. To evaluate the effectiveness and safety of ventricular septal occluder devices (VSOD) for the treatment of Gastro-tracheal fistula (GTF). METHODS: From January 2020 to May 2022, 14 patients with GTF underwent VSOD under real-time fluoroscopy. The technical success, complications, quality of life (QoL), Eastern Cooperative Oncology Group (ECOG) score, Karnofsky score, and median overall survival (mOS) were recorded and analyzed. RESULTS: Technical success, and major complication rates were 71.4%, and 14.3%, respectively. Both the ECOG and the Karnofsky score showed significant improvement at the 2-month evaluation compared with the pretreatment value (p<0.05). For QoL, general health, physical function, vitality, role physical, and social function all improved at the 2-month evaluation (p<0.05), but bodily pain, role emotion, and mental health showed no significant difference (P>0.05). During the mean follow-up of 9.6 months, eight patients were alive, and the mOS was 11.4 months (95% CI, 8.5-14.3). CONCLUSIONS: VSOD is a simple and safe technique for GTF treatment, but long-term observation is needed at multiple centers to confirm our findings.

8.
Clin Radiol ; 79(4): e500-e510, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38242804

RESUMO

AIM: To explore the value of a radiomics model based on enhanced computed tomography (CT) in differentiating anterior mediastinal lymphoma (AML) and thymoma without myasthenia gravis (MG) and calcification. MATERIALS AND METHODS: The present study analysed patients who were diagnosed histologically with AML and thymoma in three independent institutions. All pre-treatment patients underwent enhanced CT. In the training group of patients from institutions 1 (the First Affiliated Hospital of Kunming Medical University) and 3 (the Yunnan Cancer Hospital), two radiologists independently analysed the enhanced CT images and performed manual segmentation of each tumour. Radiomics features were screened using interobserver interclass coefficient (ICC) analysis, feature correlation analysis, and L1 regularisation. The discriminative efficacy of the logistic regression model was evaluated using receiver operating characteristic (ROC) analysis. Validation group of patients from institution 2 (the Second Affiliated Hospital of Zhejiang University School of Medicine) was used to validate the proposed models. RESULTS: A total of 114 patients were enrolled in this study and 1,743 radiomics features were extracted from the enhanced CT images. After feature screening, the remaining 37 robust radiomics features were used to construct the model. In the training group, the AUC of the model was 0.987 (95% confidence interval [CI]: 0.976-0.999), the sensitivity, specificity, and accuracy were 0.912, 0.946, and 0.924, respectively. In the validation group, the AUC of the model was 0.798 (95% CI: 0.683-0.913), the sensitivity, specificity, and accuracy were 0.760, 0.700, and 0.743, respectively. CONCLUSION: The radiomics model created provided effective information to assist in the selection of clinical strategies, thus reducing unnecessary procedures in patients with AML and guiding direct surgery in patients with thymoma to avoid biopsy.


Assuntos
Calcinose , Leucemia Mieloide Aguda , Linfoma , Miastenia Gravis , Timoma , Neoplasias do Timo , Humanos , Timoma/diagnóstico por imagem , Mediastino , Radiômica , China , Neoplasias do Timo/diagnóstico por imagem , Linfoma/diagnóstico por imagem , Miastenia Gravis/complicações , Miastenia Gravis/diagnóstico por imagem , Estudos Retrospectivos
9.
Clin Radiol ; 79(4): e592-e598, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38320942

RESUMO

AIM: To investigate differences in iron deposition between infarct and normal cerebral arterial regions in acute ischaemic stroke (AIS) patients using quantitative susceptibility mapping (QSM). MATERIALS AND METHODS: Forty healthy controls and 40 AIS patients were recruited, and their QSM images were obtained. There were seven regions of interest (ROIs) in AIS patients, including the infarct regions of responsible arteries (R1), the non-infarct regions of responsible arteries (R2), the contralateral symmetrical sites of lesions (R3), and the non-responsible cerebral arterial regions (R4, R5, R6, R7). For the healthy controls, the cerebral arterial regions corresponding to the AIS patient group were selected as ROIs. The differences in corresponding ROI susceptibilities between AIS patients and healthy controls and the differences in susceptibilities between infarcted and non-infarct regions in AIS patients were compared. RESULTS: The susceptibilities of infarct regions in AIS patients were significantly higher than those in healthy controls (p<0.0001). There was no significant difference in non-infarct regions between the two groups (p>0.05). The susceptibility of the infarct regions in AIS patients was significantly higher than those of the non-infarct region of responsible artery and non-responsible cerebral arterial regions (p<0.01). CONCLUSIONS: Abnormal iron deposition detected by QSM in the infarct regions of AIS patients may not affect iron levels in the non-infarct regions of responsible arteries and normal cerebral arteries, which may open the door for potential new diagnostic and treatment strategies.


Assuntos
Isquemia Encefálica , AVC Isquêmico , Acidente Vascular Cerebral , Humanos , Isquemia Encefálica/diagnóstico por imagem , Acidente Vascular Cerebral/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Artérias Cerebrais/diagnóstico por imagem , Encéfalo , Infarto , Ferro , Mapeamento Encefálico/métodos
10.
Clin Radiol ; 2024 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-38821756

RESUMO

AIM: To validate the inter-equipment generality of the radiomics based on PET images to predict the EGFR mutation status of patients with non-small cell lung cancer. MATERIALS AND METHODS: Patients were retrospectively collected in the departments of nuclear medicine of Heyi branch (Siemens equipment) and East branch (General Electric (GE) equipment) of the first affiliated hospital of Zhengzhou university. 5 predicting logistic regression models were established. The 1st one was trained and tested by the GE dataset; The 2nd one was trained and tested by the Siemens dataset; The 3rd one was trained and tested by the mixed dataset consisting of GE and Siemens. The 4th one was trained by GE and tested by Siemens; The 5th one was trained by Siemens and tested by GE. RESULTS: For the 1st ∼ 5th models, the mean values of AUCs for training/testing datasets were 0.78/0.73, 0.74/0.72, 0.75/0.70, 0.74/0.65 and 0.68/0.63, respectively. CONCLUSION: The AUCs of the models trained and tested on the datasets from the same equipment were higher than those for different equipment. The inter-equipment generality of the radiomics was not good enough in clinical practice.

11.
Clin Radiol ; 2024 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-38789330

RESUMO

AIM: To develop and validate a deep learning (DL) algorithm for the automated detection and classification of carotid artery plaques (CAPs) on computed tomography angiography (CTA) images. MATERIALS AND METHODS: This retrospective study enrolled 400 patients (300 in the Center Ⅰ and 100 in Ⅱ). Three radiologists co-labeled CAPs, and their revised calcification status (noncalcified, mixed, and calcified) was regarded as ground truth. Center Ⅰ patients were randomly divided into training and internal validation datasets, while Center Ⅱ patients served as the external validation dataset. Carotid artery regions were segmented using a modified 3D-UNet network, followed by CAPs detection and classification using a ResUNet-based architecture in a two-step DL system. The DL model's detection and classification performance were evaluated on the validation dataset using precision-recall curve, free-response receiver operating characteristic (fROC) curve, Cohen's kappa, and ROC curve analysis. RESULTS: The DL model had achieved 83.4% sensitivity at 3.0 false positives (FPs)/CTA scan in internal validation and 78.9% in external validation. F1-scores were 0.764 and 0.769 at the optimal threshold, and area under fROC curves were 0.756 and 0.738, respectively, indicating good overall accuracy for CAP detection. The DL model also showed good performance for the ternary classification of CAPs, with Cohen's kappa achieved 0.728 and 0.703 in both validation datasets. CONCLUSION: This study demonstrated the feasibility of using a fully automated DL-based algorithm for the detection and ternary classification of CAPs, which could be helpful for the workloads of radiologists.

12.
Clin Radiol ; 79(3): 230-236, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38092646

RESUMO

AIM: To assess the accuracy of Magnetic Resonance Index of Activity (MaRIA) in evaluating therapeutic efficacy in Crohn's disease (CD) patients with different activity levels using ileocolonoscopy as the reference standard. MATERIALS AND METHODS: Forty-eight patients underwent magnetic resonance enterography (MRE) and ileocolonoscopy at baseline, week 26, and week 52, along with the Simple Endoscopic Score for Crohn's Disease (SES-CD) and MaRIA scores. According to the SES-CD score at baseline, all patients were subdivided into mild, moderate, and severe activity subgroups. The identification of endoscopic mucosal healing (MH) was explored primarily. Moreover, the Crohn's Disease Activity Index (CDAI), C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), procalcitonin (PCT), and interleukin-6 (IL-6) levels were collected and analysed. RESULTS: MaRIA correlated significantly with SES-CD and CRP at baseline, week 26, and week 52. The discrepancies in MaRIA and SES-CD were statistically significant before and after treatment. MaRIA = 24.43 and ΔMaRIA = 12.77 as the cut-off points were found to have high diagnostic accuracy for predicting MH. MaRIA (p<0.001), SES-CD (p<0.001), CRP (p<0.05), ESR (p<0.05), and CDAI score (p<0.05) in patients with MH were considerably decreased compared to those in patients without MH. CONCLUSIONS: MRE has good application value in evaluating the therapeutic response of CD patients treated with biological agents. MaRIA is a reliable indicator in the follow-up of CD patients, which is strongly correlated with SES-CD, and it has high accuracy in predicting endoscopic MH.


Assuntos
Doença de Crohn , Humanos , Doença de Crohn/diagnóstico por imagem , Doença de Crohn/tratamento farmacológico , Imageamento por Ressonância Magnética , Espectroscopia de Ressonância Magnética , Índice de Gravidade de Doença
13.
J Endocrinol Invest ; 2024 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-38907823

RESUMO

BACKGROUND AND PURPOSE: Subclinical hypothyroidism (SCH) has been identified to be associated with implantation failure, in which the dysfunction of trophoblast cells is involved. In this study, the transcriptomics of aborted placenta from SCH rats were analyzed. Jupiter microtubule-associated homolog 2 (JPT2) was downregulated in the aborted placenta. This study aims to investigate its role in SCH-associated miscarriage. METHODS: Spontaneous abortion was observed in SCH rats generated by thyroidectomy combined with levothyroxine administration. The transcriptomics analysis was performed using aborted placenta. Afterward, the effects of JPT2 on trophoblast cells were explored using gain-and loss-of-function experiments. RESULTS: Transcriptomics analysis showed 1286 downregulated genes and 2300 upregulated genes in the aborted placenta, and JPT2 was significantly downregulated in the aborted placenta from SCH rats. Afterward, gain-and loss-of-function experiments exhibited that overexpression of JPT2 promoted the proliferation, migration, invasion, spheroid formation of HTR-8/SVneo trophoblast cells and their attachment to endometrial stromal cells, while these biological behaviors were suppressed by JPT2 knockdown. Furthermore, JPT2 accelerated the transcription of leptin receptor (LEPR), and activated signal transducer and activator of transcription 3 (STAT3) signal in a transcription factor AP-2γ-dependent manner. In addition, silencing of LEPR abolished the role of JPT2. CONCLUSION: Our results revealed that JPT2, which was downregulated in the aborted placenta from SCH rats, promoted proliferation, migration, invasion, spheroid formation, and attachment of trophoblast cells via regulating LEPR/STAT3 axis as a transcription co-factor. It is indicated that low expression of JPT2 may contribute to the abortion in individuals with SCH.

14.
J Endocrinol Invest ; 47(3): 535-546, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37524979

RESUMO

PURPOSE: Diabetes and dyslipidemia are among the most common chronic diseases with increasing global disease burdens, and they frequently occur together. The study aimed to investigate differences in the heritability of glycemic traits and serum lipid indicators and differences in overlapping genetic and environmental influences between them across age groups. METHODS: This study included 1189 twin pairs from the Chinese National Twin Registry and divided them into three groups: aged ≤ 40, 41-50, and > 50 years old. Univariate and bivariate structural equation models (SEMs) were conducted on glycemic indicators and serum lipid indicators, including blood glucose (GLU), glycated hemoglobin A1c (HbA1c), total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C), in the total sample and three age groups. RESULTS: All phenotypes showed moderate to high heritability (0.37-0.64). The heritability of HbA1c demonstrated a downward trend with age (HbA1c: 0.50-0.79), while others remained relatively stable (GLU: 0.55-0.62, TC: 0.58-0.66, TG: 0.50-0.63, LDL-C: 0.24-0.58, HDL-C: 0.31-0.57). The bivariate SEMs demonstrated that GLU and HbA1c were correlated with each serum lipid indicator (0.10-0.17), except HDL-C. Except for HbA1c and LDL-C, as well as HbA1c and HDL-C, differences in genetic correlations underlying glycemic traits and serum lipids between age groups were observed, with the youngest group showing a significantly higher genetic correlation than the oldest group. CONCLUSION: Across the whole adulthood, genetic influences were consistently important for GLU, TC, TG, LDL-C and HDL-C, and age may affect the shared genetic influences between glycemic traits and serum lipids. Further studies are needed to elucidate the role of age in the interactions of genes related to glycemic traits and serum lipids.


Assuntos
Glicemia , Lipídeos , Adulto , Humanos , Pessoa de Meia-Idade , Causalidade , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Fenótipo , Triglicerídeos/sangue , População do Leste Asiático , Hemoglobinas Glicadas , Lipídeos/sangue
15.
J Endocrinol Invest ; 47(6): 1531-1544, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38147289

RESUMO

BACKGROUND: Palmitic acid (PA), the major saturated fatty acid in the blood, often induces the initiation and progression of diabetic kidney disease (DKD). However, the underlying mechanism remains unclear. DACH1 is an important regulator of kidney functions. Herein, we investigated the roles of DACH1 in PA-induced kidney injury. METHODS: Clinical data from the NHANES database were subjected to analyse the association between serum PA (sPA), blood glucose and kidney function. Molecular docking of PA was performed with DACH1. Immunohistochemistry, cell viability, annexin V/7-AAD double staining, TUNEL assay, immunofluorescent staining, autophagic flux analysis, qRT-PCR and western blot were performed. RESULTS: Clinical data confirmed that sPA was increased significantly in the pathoglycemia individuals compared with controls and correlated negatively with renal function. Our findings suggested that PA could dock with DACH1. DACH1 enhances cell viability by inhibiting apoptosis and attenuating autophagy blockage induced by PA. Furthermore, the results demonstrated that DACH1 ameliorated inflammation and fibrosis through TLR4/MyD88/NF-κB and TGF-ß/Smad signalling pathway in PA-treated renal tubular epithelial cell line (HK-2). CONCLUSIONS: This study proved that sPA presents a risk factor for kidney injuries and DACH1 might serve as a protective target against renal function deterioration in diabetic patients.


Assuntos
Túbulos Renais , Fator 88 de Diferenciação Mieloide , NF-kappa B , Ácido Palmítico , Transdução de Sinais , Receptor 4 Toll-Like , Fator de Crescimento Transformador beta , Humanos , Receptor 4 Toll-Like/metabolismo , Transdução de Sinais/fisiologia , Fator 88 de Diferenciação Mieloide/metabolismo , Fator 88 de Diferenciação Mieloide/genética , NF-kappa B/metabolismo , Fator de Crescimento Transformador beta/metabolismo , Masculino , Túbulos Renais/patologia , Túbulos Renais/metabolismo , Proteínas do Olho/metabolismo , Proteínas do Olho/genética , Feminino , Proteínas Smad/metabolismo , Nefropatias Diabéticas/metabolismo , Nefropatias Diabéticas/patologia , Nefropatias Diabéticas/etiologia , Apoptose , Pessoa de Meia-Idade , Adulto , Fatores de Transcrição/metabolismo , Fatores de Transcrição/genética
16.
J Endocrinol Invest ; 47(6): 1467-1476, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38112910

RESUMO

BACKGROUND: Acne vulgaris is a prevalent skin condition. We have found that some acromegaly patients have acne. However, no study has examined the relationship between acromegaly and acne. OBJECTIVE: To explore prevalence and correlation of adult acne in patients with acromegaly. METHODS: For this cross-sectional study, we collected questionnaires, clinical information, and laboratory test results of acromegaly patients from January 2022 to December 2022 at Huashan Hospital. Of the 133 questionnaires returned, 123 had valid responses. RESULTS: Of the 123 patients with acromegaly enrolled in this study, 54.5% had adult acne. No statistically significant difference was found in prevalence between male and female patients. 61.2% of adult acne patients reported late-onset acne. Late-onset acne patients first developed acne years before acromegaly diagnosis (mean of 5.6 years for male and 4.5 years for female patients). Some acne patients have received traditional anti-acne treatment. Moreover, 31% of the patients reported no improvement, and only 3.5% of patients claimed complete resolution of acne after treatment. Before acromegaly treatment, the prevalence of adult acne was 51.2%, with mild acne accounting for 73.0%, moderate acne accounting for 23.8%, and severe acne accounting for 3.2%. After acromegaly treatment, the prevalence of adult acne was significantly decreased to 37.4% (P = 0.007). An overall decrease in acne severity was noted, with 93.5%, 6.5%, and 0% having mild, moderate, and severe acne, respectively. A total of 83.6% of the patients had self-assessed acne remission, and 33.3% of the patients reported complete acne resolution. However, 9.0% of patients reported that their condition had worsened after acromegaly treatment. After treatment, GH, IGF-1, IGF-1 index, insulin levels, and HOMA-IR decreased significantly in all patients with acromegaly (P < 0.05). Acne remission correlated positively with IGF-1 levels, but not with GH levels. The relationship between acromegaly and acne remains to be elucidated. CONCLUSIONS: Our findings provide preliminary evidence of the high prevalence of adult acne in acromegaly patients, and a high rate of late-onset acne as well. Traditional anti-acne treatments are less effective. Acne could be considerably relieved by treating acromegaly. Acne remission positively correlated with IGF-1 decline as well, which revealed the correlation between acne and IGF-1.


Assuntos
Acne Vulgar , Acromegalia , Humanos , Acne Vulgar/epidemiologia , Acromegalia/epidemiologia , Acromegalia/sangue , Acromegalia/terapia , Acromegalia/complicações , Masculino , Feminino , Estudos Transversais , Adulto , Estudos Retrospectivos , Prevalência , Pessoa de Meia-Idade , Adulto Jovem , Idoso
17.
J Endocrinol Invest ; 2024 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-38536656

RESUMO

PURPOSE: Primary aldosteronism (PA) diagnosis is affected by antihypertensive drugs that are commonly taken by patients with suspected PA. In this study, we developed and validated a diagnostic model for screening PA without drug washout. METHODS: We retrospectively analyzed 1095 patients diagnosed with PA or essential hypertension. Patients were randomly grouped into training and validation sets at a 7:3 ratio. Baseline characteristics, plasma aldosterone concentration (PAC), and direct renin concentration (DRC) before and after drug washout were separately recorded, and the aldosterone-to-renin ratio (ARR) was calculated. RESULTS: PAC and ARR were higher and direct renin concentration was lower in patients with PA than in patients with essential hypertension. Furthermore, the differences in blood potassium and sodium concentrations and hypertension grades between the two groups were significant. Using the abbreviations potassium (P), ARR (A), PAC (P), sodium (S), and hypertension grade 3 (3), the model was named PAPS3. The PAPS3 model had a maximum score of 10, with the cutoff value assigned as 5.5; it showed high sensitivity and specificity for screening PA in patients who exhibit difficulty in tolerating drug washout. CONCLUSION: PA screening remains crucial, and standard guidelines should be followed for patients to tolerate washout. The PAPS3 model offers an alternative to minimize risks and enhance diagnostic efficiency in PA for those facing washout challenges. Despite its high accuracy, further validation of this model is warranted through large-scale clinical studies.

18.
Public Health ; 227: 1-8, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38096620

RESUMO

OBJECTIVE: Muscle strength decline and vitamin D deficiency are coexisting conditions associated with multiple adverse health outcomes. This prospective study aimed to investigate the multiplicative and additive interactions between handgrip strength (HS) and serum 25-hydroxyvitamin D [25(OH)D] on all-cause mortality in Chinese community-dwelling older adults. STUDY DESIGN: This is a population-based cohort study. METHODS: 2635 older adults (85.15 ± 12.01 years) were recruited from the Chinese Longitudinal Healthy Longevity Survey (2012-2018). Low HS was defined according to the Asian Working Group for Sarcopenia 2019 updated consensus (<28 kg for men and <18 kg for women). Serum 25(OH)D < 50 nmol/L were defined as vitamin D deficiency. Cox proportional hazard models were used to examine the association of HS and 25(OH)D with all-cause mortality. Socio-demographics, health status, and clinical characteristics were included as covariates. RESULTS: 1715 (65.09 %) and 1885 (71.54 %) participants had low HS and vitamin D deficiency, respectively. During a median follow-up of 3.52 years, 1107 older people died. After multivariable adjustment, both HS and 25(OH)D levels were inversely associated with all-cause mortality risk (Ps < 0.001). The hazard ratios (HRs) of low HS and vitamin D deficiency for all-cause mortality were 1.73 (95 % CI: 1.41-2.13) and 1.61 (95 % CI: 1.32-1.93), respectively. Although significant multiplicative interactions were not found, the association between low HS and all-cause mortality was attenuated in the higher 25(OH)D subgroup than in the lower 25(OH)D subgroup (stratified by 50 nmol/L). The multiple-adjusted HR of mortality for combined low HS and vitamin D deficiency was 2.18 (95 % CI: 1.73-2.56), which was higher than that for these two conditions alone. Significant additive interactions between low HS and vitamin D deficiency on mortality were observed (relative excess risk due to interaction: 0.71, 95 % CI: 0.37-1.05). CONCLUSIONS: Low HS and low 25(OH)D levels synergistically increased the risk of all-cause mortality. Our results added new insights to the priority of early detection for older adults with comorbid muscle strength decline and vitamin D deficiency.


Assuntos
Vida Independente , Deficiência de Vitamina D , Masculino , Humanos , Feminino , Idoso , Estudos Prospectivos , Estudos de Coortes , Força da Mão , Deficiência de Vitamina D/complicações , Vitamina D
19.
Public Health ; 231: 64-70, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38636278

RESUMO

OBJECTIVES: Workplace-related factors are associated with the risk of depression. Despite implementation of workplace health promotion (WHP) programmes in China to promote the physical and mental well-being of workers, the relationship between WHP and depression has received limited attention. This study investigated the association between WHP service utilisation and depressive symptoms among workers. STUDY DESIGN: This was a cross-sectional survey. METHODS: A researcher-designed questionnaire was used to collect information on socio-demographic and occupational characteristics, WHP service utilisation, and mental health status. The Lasso method was used for variable selection to achieve dimension reduction, and logistic regression was used to assess the association between WHP service utilisation and depressive symptoms. RESULTS: The analysis included 11,710 workers, of whom 17.0% had depressive symptoms. Lasso regression resulted in 6 of 18 WHP services showing significant negative associations with depressive symptoms, including occupational safety training, mental health services, health check-ups, sports activities, fitness rooms, and healthy canteens. The logistic regression results showed that, after adjusting for sociodemographic and occupational factors, utilisation of these six services was associated with a decreased likelihood of depressive symptoms. The adjusted odds ratio (aOR) was 0.84 (95% confidence interval [CI]: 0.73-0.96) for occupational safety training, aOR: 0.82 (95% CI: 0.68-0.99) for mental health services, aOR: 0.80 (95% CI: 0.71-0.90) for health check-ups, aOR: 0.68 (95% CI: 0.57-0.80) for sports activities, aOR: 0.59 (95% CI: 0.47-0.74) for fitness rooms and aOR: 0.72 (95% CI: 0.59-0.87) for healthy canteens. CONCLUSIONS: Utilisation of WHP services was associated with a lower prevalence of depressive symptoms. Implementation of WHP services and the provision of a supportive workplace environment should be prioritised to benefit the mental health of workers.


Assuntos
Depressão , Promoção da Saúde , Local de Trabalho , Humanos , Masculino , Feminino , Estudos Transversais , Depressão/epidemiologia , Adulto , Pessoa de Meia-Idade , China/epidemiologia , Local de Trabalho/psicologia , Local de Trabalho/estatística & dados numéricos , Inquéritos e Questionários , Serviços de Saúde do Trabalhador/estatística & dados numéricos , Adulto Jovem , Saúde Ocupacional/estatística & dados numéricos
20.
Public Health ; 226: 91-98, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38029699

RESUMO

OBJECTIVES: National-level data on the incidence of retinopathy of prematurity (ROP) in different regions of China is insufficient. This study aimed to compare ROP incidences and care practices in different regions of China and their relationship with regional gross domestic product (GDP) per capita. STUDY DESIGN: Retrospective cohort study. METHODS: All infants born at <32 weeks gestational age (GA) and admitted to 70 neonatal intensive care units (NICUs) from January 1, 2019, to December 31, 2020, were enrolled. Hospitals were categorised into three regional groups according to geographical locations and GDP per capita from high to low: Eastern, Central, and Western China. The incidence of death or ROP, and care practices were compared among the groups. RESULTS: A total of 18,579 infants were enrolled. Median GA was 29.9 (interquartile range 28.4-31.0) weeks and birth weight was 1318.1 (317.2) g. The percentage of GA <28 weeks, complete administration of antenatal steroids, and weight gain velocity during NICU stay were highest in Eastern China and lowest in Western China (all P < 0.01). In Eastern, Central, and Western China, the rates of death or any stage of ROP were 33.3%, 38.5%, and 39.2%, respectively (P < 0.01). CONCLUSIONS: There were considerable regional disparities in ROP incidence in preterm infants with GA <32 weeks in China. The incidence of death or ROP ranged from high to low in Western, Central, and Eastern China.


Assuntos
Recém-Nascido Prematuro , Retinopatia da Prematuridade , Gravidez , Lactente , Recém-Nascido , Humanos , Feminino , Idade Gestacional , Incidência , Retinopatia da Prematuridade/epidemiologia , Estudos Retrospectivos , Fatores de Risco , Peso ao Nascer , China/epidemiologia
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