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Objective: To further improve the understanding of paroxysmal nocturnal hemoglobinuria (PNH), we retrospectively analyzed and summarized the clinical characteristics, treatment status, and survival status of patients with PNH in Zhejiang Province. Methods: This study included 289 patients with PNH who visited 20 hospitals in Zhejiang Province. Their clinical characteristics, comorbidity, laboratory test results, and medications were analyzed and summarized. Results: Among the 289 patients with PNH, 148 males and 141 females, with a median onset age of 45 (16-87) years and a peak onset age of 20-49 years (57.8% ). The median lactic dehydrogenase (LDH) level was 1 142 (604-1 925) U/L. Classified by type, 70.9% (166/234) were classical, 24.4% (57/234) were PNH/bone marrow failure (BMF), and 4.7% (11/234) were subclinical. The main clinical manifestations included fatigue or weakness (80.8%, 235/289), dizziness (73.4%, 212/289), darkened urine color (66.2%, 179/272), and jaundice (46.2%, 126/270). Common comorbidities were hemoglobinuria (58.7% ), renal dysfunction (17.6% ), and thrombosis (15.0% ). Moreover, 82.3% of the patients received glucocorticoid therapy, 70.9% required blood transfusion, 30.7% used immunosuppressive agents, 13.8% received anticoagulant therapy, and 6.3% received allogeneic hematopoietic stem cell transplantation. The 10-year overall survival (OS) rate was 84.4% (95% CI 78.0% -91.3% ) . Conclusion: Patients with PNH are more common in young and middle-aged people, with a similar incidence rate between men and women. Common clinical manifestations include fatigue, hemoglobinuria, jaundice, renal dysfunction, and recurrent thrombosis. The 10-year OS of this group is similar to reports from other centers in China.
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Hemoglobinúria Paroxística , Humanos , Hemoglobinúria Paroxística/epidemiologia , Hemoglobinúria Paroxística/diagnóstico , Hemoglobinúria Paroxística/terapia , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Adolescente , Estudos Retrospectivos , Adulto Jovem , Idoso , China/epidemiologia , Idoso de 80 Anos ou maisRESUMO
Rapid and accurate diagnostic technologies are crucial for early detection and diagnosis of diseases. Electrowetting-on-dielectric digital microfluidics, with its high-precision detection and high-throughput screening capabilities, significantly enhances the accuracy and efficiency in early disease diagnosis and personalized treatment, enabling swift disease detection and widespread screening. This article provides a comprehensive review of the working principles and fabrication processes of digital microfluidic chips based on electrowetting on dielectric method. It details the latest research progress in the areas of nucleic acids, proteins, and cells, organizes the commercialization of digital microfluidics technology, and finally discusses the current challenges and future directions of digital microfluidic chips.
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Eletroumectação , Microfluídica , Microfluídica/métodos , Eletroumectação/métodos , Humanos , Técnicas Analíticas Microfluídicas/instrumentação , Técnicas Analíticas Microfluídicas/métodosRESUMO
Malignant peripheral nerve sheath tumor (MPNST) frequently metastasizes to the lungs, although pleural metastasis is rare. This article reported a case of pleural metastasis of MPNST. The patient was a young man who presented with 1 week of shortness of breath with dry cough. He had a history of malignant peripheral nerve sheath tumor. The patient was diagnosed with MPNST pleural metastasis after a thoracoscopic pleural biopsy, which revealed short spindle cell hyperplasia, immunohistochemical staining for S-100(+), SOX-10(+), Ki-67(+) with a positive index of 20%, and H3K27Me3(-) in the pleural pathology.
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Neoplasias de Bainha Neural , Neoplasias Pleurais , Humanos , Masculino , Neoplasias Pleurais/secundário , Neoplasias Pleurais/patologia , Neoplasias de Bainha Neural/patologia , Neoplasias de Bainha Neural/secundário , Neoplasias de Bainha Neural/diagnóstico , AdultoRESUMO
Type 2 diabetes (T2D) is a major risk factor for heart failure (HF) and has elevated incidence among individuals with HF. Since genetics and HF can independently influence T2D, collider bias may occur when T2D (i.e., collider) is controlled for by design or analysis. Thus, we conducted a genome-wide association study (GWAS) of diabetes-related HF with correction for collider bias. We first performed a GWAS of HF to identify genetic instrumental variables (GIVs) for HF and to enable bidirectional Mendelian randomization (MR) analysis between T2D and HF. We identified 61 genomic loci, significantly associated with all-cause HF in 114,275 individuals with HF and over 1.5 million controls of European ancestry. Using a two-sample bidirectional MR approach with 59 and 82 GIVs for HF and T2D, respectively, we estimated that T2D increased HF risk (odds ratio [OR] 1.07, 95% confidence interval [CI] 1.04-1.10), while HF also increased T2D risk (OR 1.60, 95% CI 1.36-1.88). Then we performed a GWAS of diabetes-related HF corrected for collider bias due to the study design of index cases. After removing the spurious association of TCF7L2 locus due to collider bias, we identified two genome-wide significant loci close to PITX2 (chromosome 4) and CDKN2B-AS1 (chromosome 9) associated with diabetes-related HF in the Million Veteran Program and replicated the associations in the UK Biobank. Our MR findings provide strong evidence that HF increases T2D risk. As a result, collider bias leads to spurious genetic associations of diabetes-related HF, which can be effectively corrected to identify true positive loci.
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Diabetes Mellitus Tipo 2 , Estudo de Associação Genômica Ampla , Insuficiência Cardíaca , Análise da Randomização Mendeliana , Humanos , Insuficiência Cardíaca/genética , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/complicações , Masculino , Feminino , Polimorfismo de Nucleotídeo Único , Predisposição Genética para Doença , Pessoa de Meia-Idade , Fatores de Risco , Idoso , Inibidor de Quinase Dependente de Ciclina p15/genética , População Branca/genética , Viés , Proteínas de Homeodomínio/genética , Fatores de Transcrição/genéticaRESUMO
Cancer immunotherapy with autologous chimeric antigen receptor (CAR) T cells faces challenges in manufacturing and patient selection that could be avoided by using 'off-the-shelf' products, such as allogeneic CAR natural killer T (AlloCAR-NKT) cells. Previously, we reported a system for differentiating human hematopoietic stem and progenitor cells into AlloCAR-NKT cells, but the use of three-dimensional culture and xenogeneic feeders precluded its clinical application. Here we describe a clinically guided method to differentiate and expand IL-15-enhanced AlloCAR-NKT cells with high yield and purity. We generated AlloCAR-NKT cells targeting seven cancers and, in a multiple myeloma model, demonstrated their antitumor efficacy, expansion and persistence. The cells also selectively depleted immunosuppressive cells in the tumor microenviroment and antagonized tumor immune evasion via triple targeting of CAR, TCR and NK receptors. They exhibited a stable hypoimmunogenic phenotype associated with epigenetic and signaling regulation and did not induce detectable graft versus host disease or cytokine release syndrome. These properties of AlloCAR-NKT cells support their potential for clinical translation.
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Objective: To integrate long-term daily continuous glucose monitoring (CGM) device data with electronic health records (EHR) for patients with type 1 and type 2 diabetes (T1D and T2D) in the national Veterans Affairs Healthcare System to assess real-world patterns of CGM use and the reliability of EHR-based CGM information. Research Design and Methods: This observational study used Dexcom CGM device data linked with EHR (from 2015 to 2020) for a large national cohort of patients with diabetes. We tracked the initiation and consistency of CGM use, assessed concordance of CGM use and measures of glucose control between CGM device data and EHR records, and examined results by age, ethnicity, and diabetes type. Results: The time from pharmacy release of CGM to patients to initiation of uploading CGM data to Dexcom servers averaged 3 weeks but demonstrated wide variation among individuals; importantly, this delay decreased markedly over the later years. The average daily wear time of CGM exceeded 22 h over nearly 3 years of follow-up. Patterns of CGM use were generally consistent across age, race/ethnicity groups, and diabetes type. There was strong concordance between EHR-based estimates of CGM use and Dexcom CGM wear time and between estimates of glucose control from both sources. Conclusions: The study demonstrates our ability to reliably integrate CGM devices and EHR data to provide valuable insights into CGM use patterns. The results indicate in the real-world environment that CGM is worn consistently over many years for both patients with T1D and T2D within the Veterans Affairs Healthcare System and is similar across major race/ethnic groups and age-groups.
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2D materials, given their form-factor, high surface-to-volume ratio, and chemical functionality have immense use in sensor design. Engineering 2D heterostructures can result in robust combinations of desirable properties but sensor design methodologies require careful considerations about material properties and orientation to maximize sensor response. This study introduces a sensor approach that combines the excellent electrical transport and transduction properties of graphite film with chemical reactivity derived from the edge sites of semiconducting molybdenum disulfide (MoS2) through a two-step chemical vapour deposition method. The resulting vertical heterostructure shows potential for high-performance hybrid chemiresistors for gas sensing. This architecture offers active sensing edge sites across the MoS2 flakes. We detail the growth of vertically oriented MoS2 over a nanoscale graphite film (NGF) cross-section, enhancing the adsorption of analytes such as NO2, NH3, and water vapor. Raman spectroscopy, density functional theory calculations and scanning probe methods elucidate the influence of chemical doping by distinguishing the role of MoS2 edge sites relative to the basal plane. High-resolution imaging techniques confirm the controlled growth of highly crystalline hybrid structures. The MoS2/NGF hybrid structure exhibits exceptional chemiresistive responses at both room and elevated temperatures compared to bare graphitic layers. Quantitative analysis reveals that the sensitivity of this hybrid sensor surpasses other 2D material hybrids, particularly in parts per billion concentrations.
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During heart failure, gene and protein expression profiles undergo extensive compensatory and pathological remodeling. We previously observed that fast skeletal myosin binding protein-C (fMyBP-C) is upregulated in diseased mouse hearts. While fMyBP-C shares significant homology with its cardiac paralog, cardiac myosin binding protein-C (cMyBP-C), there are key differences that may affect cardiac function. However, it is unknown if the expression of fMyBP-C expression in the heart is a pathological or compensatory response. We aim to elucidate the cardiac consequence of either increased or knockout of fMyBP-C expression. To determine the sufficiency of fMyBP-C to cause cardiac dysfunction, we generated cardiac-specific fMyBP-C over-expression mice. These mice were further crossed into a cMyBP-C null model to assess the effect of fMyBP-C in the heart in the complete absence of cMyBP-C. Finally, fMyBP-C null mice underwent transverse aortic constriction (TAC) to define the requirement of fMyBP-C during heart failure development. We confirmed the upregulation of fMyBP-C in several models of cardiac disease, including the use of lineage tracing. Low levels of fMyBP-C caused mild cardiac remodeling and sarcomere dysfunction. Exclusive expression of fMyBP-C in a heart failure model further exacerbated cardiac pathology. Following 8 weeks of TAC, fMyBP-C null mice demonstrated greater protection against heart failure development. Mechanistically, this may be due to the differential regulation of the myosin super-relaxed state. These findings suggest that the elevated expression of fMyBP-C in diseased hearts is a pathological response. Targeted therapies to prevent upregulation of fMyBP-C may prove beneficial in the treatment of heart failure. Significance Statement: Recently, the sarcomere - the machinery that controls heart and muscle contraction - has emerged as a central target for development of cardiac therapeutics. However, there remains much to understand about how the sarcomere is modified in response to disease. We recently discovered that a protein normally expressed in skeletal muscle, is present in the heart in certain settings of heart disease. How this skeletal muscle protein affects the function of the heart remained unknown. Using genetically engineered mouse models to modulate expression of this skeletal muscle protein, we determined that expression of this skeletal muscle protein in the heart negatively affects cardiac performance. Importantly, deletion of this protein from the heart could improve heart function suggesting a possible therapeutic avenue.
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Objectives To screen high active volatile organic compounds (VOCs)-producing Trichoderma isolates against strawberry gray mold caused by Botrytis cinerea, and to explore their antagonistic mode of action against the pathogen. VOCs produced by nine Trichoderma isolates (Trichoderma atroviride T1 and T3; Trichoderma harzianum T2, T4 and T5; T6, T7, T8 and T9 identified as Trichoderma asperellum in this work) significantly inhibited the mycelial growth (13.9-63.0% reduction) and conidial germination (17.6-96.3% reduction) of B. cinerea, the highest inhibition percentage belonged to VOCs of T7; in a closed space, VOCs of T7 shared 76.9% and 100% biocontrol efficacy against gray mold on strawberry fruits and detached leaves, respectively, prolonged the fruit shelf-life by 3 days in presence of B. cinerea, completely protected the leaves from B. cinerea infecting; volatile metabolites of T7 damaged the cell membrane permeability and integrity of B. cinerea, thereby inhibiting the mycelial growth and conidial germination. Gas chromatography-mass spectrometry (GC-MS) analysis revealed the VOCs contain 23 potential compounds, and the majority of these compounds were categorised as alkenes, alcohols, and esters, including PEA and 6PP, which have been reported as substances produced by Trichoderma spp. T. asperellum T7 showed high biofumigant activity against mycelial growth especially conidial germination of B. cinerea and thus protected strawberry fruits and leaves from gray mold, which acted by damaging the pathogen's plasma membrane and resulting in cytoplasm leakage, was a potential biofumigant for controlling pre- and post-harvest strawberry gray mold.
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The clinical potential of current FDA-approved chimeric antigen receptor (CAR)-engineered T (CAR-T) cell therapy is encumbered by its autologous nature, which presents notable challenges related to manufacturing complexities, heightened costs, and limitations in patient selection. Therefore, there is a growing demand for off-the-shelf universal cell therapies. In this study, we have generated universal CAR-engineered NKT (UCAR-NKT) cells by integrating iNKT TCR engineering and HLA gene editing on hematopoietic stem cells (HSCs), along with an ex vivo, feeder-free HSC differentiation culture. The UCAR-NKT cells are produced with high yield, purity, and robustness, and they display a stable HLA-ablated phenotype that enables resistance to host cell-mediated allorejection. These UCAR-NKT cells exhibit potent antitumor efficacy to blood cancers and solid tumors, both in vitro and in vivo, employing a multifaceted array of tumor-targeting mechanisms. These cells are further capable of altering the tumor microenvironment by selectively depleting immunosuppressive tumor-associated macrophages and myeloid-derived suppressor cells. In addition, UCAR-NKT cells demonstrate a favorable safety profile with low risks of graft-versus-host disease and cytokine release syndrome. Collectively, these preclinical studies underscore the feasibility and significant therapeutic potential of UCAR-NKT cell products and lay a foundation for their translational and clinical development.
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Células-Tronco Hematopoéticas , Imunoterapia Adotiva , Células T Matadoras Naturais , Receptores de Antígenos Quiméricos , Humanos , Células-Tronco Hematopoéticas/metabolismo , Células-Tronco Hematopoéticas/citologia , Células-Tronco Hematopoéticas/imunologia , Animais , Receptores de Antígenos Quiméricos/imunologia , Receptores de Antígenos Quiméricos/genética , Receptores de Antígenos Quiméricos/metabolismo , Imunoterapia Adotiva/métodos , Camundongos , Células T Matadoras Naturais/imunologia , Células T Matadoras Naturais/metabolismo , Edição de Genes , Ensaios Antitumorais Modelo de Xenoenxerto , Neoplasias/terapia , Neoplasias/imunologia , Linhagem Celular Tumoral , Receptores de Antígenos de Linfócitos T/metabolismo , Receptores de Antígenos de Linfócitos T/genética , Receptores de Antígenos de Linfócitos T/imunologiaRESUMO
BACKGROUND: Heart failure (HF) is a serious condition with increasing prevalence, high morbidity, and increased mortality. Obesity is an established risk factor for HF. Fluctuation in body mass index (BMI) has shown a higher risk of cardiovascular outcomes. We investigated the association between BMI variability and incident HF. METHODS AND RESULTS: In the UK Biobank, we established a prospective cohort after excluding participants with prevalent HF or cancer at enrollment. A total of 99 368 White participants with ≥3 BMI measures during >2 years preceding enrollment were included, with a median follow-up of 12.5 years. The within-participant variability of BMI was evaluated using standardized SD and coefficient of variation. The association of BMI variability with incident HF was assessed using Fine and Gray's competing risk model, adjusting for confounding factors and participant-specific rate of BMI change. Higher BMI variability measured in both SD and coefficient of variation was significantly associated with higher risk in HF incidence (SD: hazard ratio [HR], 1.05 [95% CI, 1.03-1.08], P<0.0001; coefficient of variation: HR, 1.07 [95% CI, 1.04-1.10], P<0.0001). CONCLUSIONS: Longitudinal health records capture BMI fluctuation, which independently predicts HF incidence.
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Índice de Massa Corporal , Insuficiência Cardíaca , Obesidade , Humanos , Insuficiência Cardíaca/epidemiologia , Insuficiência Cardíaca/diagnóstico , Masculino , Feminino , Pessoa de Meia-Idade , Incidência , Obesidade/epidemiologia , Obesidade/complicações , Obesidade/diagnóstico , Estudos Prospectivos , Reino Unido/epidemiologia , Idoso , Fatores de Risco , Medição de Risco/métodos , Adulto , Fatores de TempoRESUMO
Objectives: To assess the prognostic impact of the neoadjuvant rectal (NAR) score following neoadjuvant short-course radiotherapy and consolidation chemotherapy in locally advanced rectal cancer (LARC), as well as its value in guiding decisions for adjuvant chemotherapy. Methods: Between August 2015 and August 2018, patients were eligible from the STELLAR phase III trial (NCT02533271) who received short-course radiotherapy plus consolidation chemotherapy and for whom the NAR score could be calculated. Based on the NAR score, patients were categorized into low (ï¼8), intermediate (8-16), and high (ï¼16) groups. The Kaplan-Meier method, log rank tests, and multivariate Cox proportional hazard regression models were used to evaluate the impact of the NAR score on disease-free survival (DFS). Results: Out of the 232 patients, 24.1%, 48.7%, and 27.2% had low (56 cases), intermediate (113 cases), and high NAR scores (63 cases), respectively. The median follow-up period was 37 months, with 3-year DFS rates of 87.3%, 68.3%, and 53.4% (Pï¼0.001) for the low, intermediate, and high NAR score groups. Multivariate analysis demonstrated that the NAR score (intermediate NAR score: HR, 3.10, 95% CI, 1.30-7.37, P=0.011; high NAR scores: HR=5.44, 95% CI, 2.26-13.09, Pï¼0.001), resection status (HR, 3.00, 95% CI, 1.64-5.52, Pï¼0.001), and adjuvant chemotherapy (HR, 3.25, 95% CI, 2.01-5.27, Pï¼0.001) were independent prognostic factors for DFS. In patients with R0 resection, the 3-year DFS rates were 97.8% and 78.0% for those with low and intermediate NAR scores who received adjuvant chemotherapy, significantly higher than the 43.2% and 50.6% for those who did not (Pï¼0.001, P=0.002). There was no significant difference in the 3-year DFS rate (54.2% vs 53.3%, P=0.214) among high NAR score patients, regardless of adjuvant chemotherapy. Conclusions: The NAR score is a robust prognostic indicator in LARC following neoadjuvant short-course radiotherapy and consolidation chemotherapy, with potential implications for subsequent decisions regarding adjuvant chemotherapy. These findings warrant further validation in studies with larger sample sizes.
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Quimioterapia de Consolidação , Terapia Neoadjuvante , Neoplasias Retais , Humanos , Neoplasias Retais/patologia , Neoplasias Retais/terapia , Quimioterapia Adjuvante , Prognóstico , Intervalo Livre de Doença , Modelos de Riscos Proporcionais , Masculino , Feminino , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Pessoa de Meia-Idade , Taxa de Sobrevida , RetoRESUMO
BACKGROUND: Population aging might increase the prevalence of undernutrition in older people, which increases the risk of frailty. Numerous studies have indicated that myokines are released by skeletal myocytes in response to muscular contractions and might be associated with frailty. This study aimed to evaluate whether myokines are biomarkers of frailty in older inpatients with undernutrition. METHODS: The frailty biomarkers were extracted from the Gene Expression Omnibus and Genecards datasets. Relevant myokines and health-related variables were assessed in 55 inpatients aged ≥ 65 years from the Peking Union Medical College Hospital prospective longitudinal frailty study. Serum was prepared for enzyme-linked immunosorbent assay using the appropriate kits. Correlations between biomarkers and frailty status were calculated by Spearman's correlation analysis. Multiple linear regression was performed to investigate the association between factors and frailty scores. RESULTS: The prevalence of frailty was 13.21%. The bioinformatics analysis indicated that leptin, adenosine 5'-monophosphate-activated protein kinase (AMPK), irisin, decorin, and myostatin were potential biomarkers of frailty. The frailty group had significantly higher concentrations of leptin, AMPK, and MSTN than the robust group (p < 0.05). AMPK was significantly positively correlated with frailty (p < 0.05). The pre-frailty and frailty groups had significantly lower concentrations of irisin than the robust group (p < 0.05), whereas the DCN concentration did not differ among the groups. Multiple linear regression suggested that the 15 factors influencing the coefficients of association, the top 50% were the ADL score, MNA-SF score, serum albumin concentration, urination function, hearing function, leptin concentration, GDS-15 score, and MSTN concentration. CONCLUSIONS: Proinflammatory myokines, particularly leptin, myostatin, and AMPK, negatively affect muscle mass and strength in older adults. ADL and nutritional status play major roles in the development of frailty. Our results confirm that identification of frailty relies upon clinical variables, myokine concentrations, and functional parameters, which might enable the identification and monitoring of frailty.
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Fragilidade , Desnutrição , Humanos , Idoso , Proteínas Quinases Ativadas por AMP , Fibronectinas , Fragilidade/diagnóstico , Fragilidade/epidemiologia , Pacientes Internados , Leptina , Miocinas , Miostatina , Estudos Prospectivos , Desnutrição/diagnóstico , Desnutrição/epidemiologia , BiomarcadoresRESUMO
OBJECTIVES: The association between blood pressure and frailty outcome in the middle-aged and older population remains controversial. This study aimed to examine the relationship between trajectories of systolic blood pressure (SBP) and new-onset frailty. DESIGN: Cohort study with a 7-year follow-up. SETTING AND PARTICIPANTS: Data were derived from 4 waves (2011, 2013, 2015 and 2018) of the China Health and Retirement Longitudinal Study and 6168 participants aged ≥45 years were included in the study. METHODS: The frailty index (FI) was constructed based on 40 scored items, with FI ≥ 0.25 defined as frailty. We identified the 5-year trajectory of SBP by latent class trajectory modeling. The association between SBP trajectories and frailty was explored based on hazard ratios (HR) by four Cox proportional hazards models. Furthermore, we also investigated the relationship between mean SBP and systolic blood pressure variability (SBPV) and frailty. RESULTS: 6168 participants were included in this study with a mean age of 59 years. We identified five trajectories based on SBP, which are maintained low-stable SBP (T0), moderate-stable SBP (T1), remitting then increasing SBP (T2), increasing then remitting SBP (T3), and remaining stable at high SBP levels (T4). During the 7-year follow-up period, frailty outcome occurred in 1415 participants. After adjusting for other confounders, the two trajectories labeled "T2" and "T4" were associated with a higher risk of frailty compared with T0. In addition, elevated SBP and increased SBPV were associated with risk of frailty. CONCLUSIONS: Higher risk of frailty occurred in two trajectories, remitting then increasing and remaining stable at high SBP levels, were associated with a relatively higher risk of frailty.
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Pressão Sanguínea , Fragilidade , Humanos , Masculino , Feminino , Pressão Sanguínea/fisiologia , Pessoa de Meia-Idade , Fragilidade/epidemiologia , Idoso , Estudos Longitudinais , China/epidemiologia , Idoso Fragilizado/estatística & dados numéricos , Modelos de Riscos Proporcionais , Fatores de Risco , Estudos de Coortes , Avaliação Geriátrica/métodos , Avaliação Geriátrica/estatística & dados numéricos , Hipertensão/epidemiologia , SeguimentosRESUMO
This paper demonstrates how person-focused, prevention-based, risk/needs-related, team-delivered, minimum intervention oral care (MIOC) principles and approaches can be integrated into the dental profession for the delivery of environmentally sustainable, optimal care to high-needs and high caries-risk/susceptibility patients. It highlights the potential for NHS remuneration for prevention-based, phased, personalised care pathways/plans (PCPs) within a reformed NHS dental contract system. It emphasises the importance of comprehensive and longitudinal patient risk/susceptibility assessments, prevention and stabilisation of the oral environment before considering more complex, definitive restorative work. This paper forms the first of several components of a suite of educational/information materials needed to instil confidence and implementation protocols within primary care clinical oral health care teams delivering MIOC through phased PCPs, especially when managing patients with high needs and/or disease susceptibility.
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Suscetibilidade à Cárie Dentária , Cárie Dentária , Humanos , Motivação , Atenção à Saúde , Cárie Dentária/prevenção & controle , Medição de Risco , Saúde BucalRESUMO
Importance: Body mass index (BMI; calculated as weight in kilograms divided by height in meters squared) is a commonly used estimate of obesity, which is a complex trait affected by genetic and lifestyle factors. Marked weight gain and loss could be associated with adverse biological processes. Objective: To evaluate the association between BMI variability and incident cardiovascular disease (CVD) events in 2 distinct cohorts. Design, Setting, and Participants: This cohort study used data from the Million Veteran Program (MVP) between 2011 and 2018 and participants in the UK Biobank (UKB) enrolled between 2006 and 2010. Participants were followed up for a median of 3.8 (5th-95th percentile, 3.5) years. Participants with baseline CVD or cancer were excluded. Data were analyzed from September 2022 and September 2023. Exposure: BMI variability was calculated by the retrospective SD and coefficient of variation (CV) using multiple clinical BMI measurements up to the baseline. Main Outcomes and Measures: The main outcome was incident composite CVD events (incident nonfatal myocardial infarction, acute ischemic stroke, and cardiovascular death), assessed using Cox proportional hazards modeling after adjustment for CVD risk factors, including age, sex, mean BMI, systolic blood pressure, total cholesterol, high-density lipoprotein cholesterol, smoking status, diabetes status, and statin use. Secondary analysis assessed whether associations were dependent on the polygenic score of BMI. Results: Among 92â¯363 US veterans in the MVP cohort (81â¯675 [88%] male; mean [SD] age, 56.7 [14.1] years), there were 9695 Hispanic participants, 22â¯488 non-Hispanic Black participants, and 60â¯180 non-Hispanic White participants. A total of 4811 composite CVD events were observed from 2011 to 2018. The CV of BMI was associated with 16% higher risk for composite CVD across all groups (hazard ratio [HR], 1.16; 95% CI, 1.13-1.19). These associations were unchanged among subgroups and after adjustment for the polygenic score of BMI. The UKB cohort included 65â¯047 individuals (mean [SD] age, 57.30 (7.77) years; 38â¯065 [59%] female) and had 6934 composite CVD events. Each 1-SD increase in BMI variability in the UKB cohort was associated with 8% increased risk of cardiovascular death (HR, 1.08; 95% CI, 1.04-1.11). Conclusions and Relevance: This cohort study found that among US veterans, higher BMI variability was a significant risk marker associated with adverse cardiovascular events independent of mean BMI across major racial and ethnic groups. Results were consistent in the UKB for the cardiovascular death end point. Further studies should investigate the phenotype of high BMI variability.
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AVC Isquêmico , Infarto do Miocárdio , Feminino , Masculino , Humanos , Pessoa de Meia-Idade , Índice de Massa Corporal , Estudos de Coortes , Estudos Retrospectivos , Infarto do Miocárdio/epidemiologia , HDL-ColesterolRESUMO
Objective: To investigate the prospective association of sleep duration with the development of chronic obstructive pulmonary disease (COPD) in adults in Suzhou. Methods: The study used the data of 53 269 participants aged 30-79 years recruited in the baseline survey from 2004 to 2008 and the follow-up until December 31, 2017 of China Kadoorie Biobank (CKB) conducted in Wuzhong District, Suzhou. After excluding participants with airflow limitation, self-reported chronic bronchitis/emphysema/coronary heart disease history at the baseline survey and abnormal or incomplete data, a total of 45 336 participants were included in the final analysis. The association between daily sleep duration and the risk for developing COPD was analyzed by using a Cox proportional hazard regression model, and the hazard ratio (HR) values and their 95%CI were calculated. The analysis was stratified by age, gender and lifestyle factors, and cross-analysis was conducted according to smoking status and daily sleep duration. Results: The median follow-up time was 11.12 years, with a total of 515 COPD diagnoses in the follow-up. After adjusting for potential confounders, multifactorial Cox proportional hazard regression analysis showed that daily sleep duration ≥10 hours was associated with higher risk for developing COPD (HR=1.42, 95%CI: 1.03-1.97). The cross analysis showed that excessive daily sleep duration increased the risk for COPD in smokers (HR=2.49, 95%CI: 1.35-4.59, interaction P<0.001). Conclusion: Longer daily sleep duration (≥10 hours) might increase the risk for COPD in adults in Suzhou, especially in smokers.
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Isquemia Miocárdica , Doença Pulmonar Obstrutiva Crônica , Adulto , Humanos , Estudos Prospectivos , Duração do Sono , Fatores de Risco , Doença Pulmonar Obstrutiva Crônica/diagnóstico , SonoRESUMO
For pancreatic neoplasms, the current clinical treatment strategy is mainly using standard surgical methods, including pancreaticoduodenectomy, distal pancreatectomy with splenectomy, and total pancreatectomy. Standard surgical methods require a larger resection, including resection of some surrounding organs and a large amount of pancreatic parenchyma. The endocrine and exocrine functions of the pancreas are easily damaged. Moreover, since the standard surgical procedure involves the reconstruction of the digestive tract at multiple anastomoses, there is a high risk of pancreatic, biliary, and intestinal fistulas occurring postoperatively. Therefore, function-preserving pancreatic surgery is recommended for some benign and low-grade pancreatic neoplasms. This type of surgery can treat pancreatic diseases while preserving more peripancreatic organs, pancreatic parenchyma and relatively complete digestive tract continuity, thereby improving the patient's short-term and long-term quality of life. In addition, with the development of laparoscopy and da Vinci robotic technology, minimally invasive technology-assisted pancreatic surgery has been carried out in clinical practice. They have been shown to be sufficiently safe and effective. This article reviews several common clinical pancreatic function-preserving surgical methods and their corresponding clinical applications and technical development status from the perspectives of preserving more peripancreatic organs, preserving more pancreatic parenchyma, and promoting pancreatic function recovery.
Assuntos
Laparoscopia , Neoplasias Pancreáticas , Humanos , Qualidade de Vida , Pâncreas/cirurgia , Pancreatectomia/métodos , Pancreaticoduodenectomia/métodos , Neoplasias Pancreáticas/cirurgiaRESUMO
It is well known that chemical energy can be converted to mechanical force in biological systems by motor proteins such as myosin ATPase. It is also broadly observed that constant/static mechanical signals potently induce cellular responses. However, the mechanisms that cells sense and convert the mechanical force into biochemical signals are not well understood. Calponin and transgelin are a family of homologous proteins that participate in the regulation of actin-activated myosin motor activity. An isoform of calponin, calponin 2, has been shown to regulate cytoskeleton-based cell motility functions under mechanical signaling. The expression of the calponin 2 gene and the turnover of calponin 2 protein are both under mechanoregulation. The regulation and function of calponin 2 has physiological and pathological significance, as shown in platelet adhesion, inflammatory arthritis, arterial atherosclerosis, calcific aortic valve disease, post-surgical fibrotic peritoneal adhesion, chronic proteinuria, ovarian insufficiency, and tumor metastasis. The levels of calponin 2 vary in different cell types, reflecting adaptations to specific tissue environments and functional states. The present review focuses on the mechanoregulation of calponin and transgelin family proteins to explore how cells sense steady tension and convert the force signal to biochemical activities. Our objective is to present a current knowledge basis for further investigations to establish the function and mechanisms of calponin and transgelin in cellular mechanoregulation.