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RATIONALE: This study reports the first case of congenital hypothyroidism (CH) and alpha thalassemia in a child in China, with anemia and muscle damage as the main manifestations. Analyzing and studying this case is of great significance in reducing missed and misdiagnosed CH and will provide a clinical strategy for treating these patients. PATIENT CONCERNS: Child, female, 2 years and 7 months old, the child appeared dispirited, had poor appetite, shallow complexion, reduced activities with anemia, elevated muscle enzymes, height, and growth retardation. DIAGNOSES: The child was diagnosed with CH with alpha thalassemia. INTERVENTIONS: The patient was treated with levothyroxine sodium and anemia correction. OUTCOMES: The children's current spirit, appetite, red face, normal limb activity, physical development, and intelligence were significantly better than those of normal children of the same age. CONCLUSIONS: CH with alpha thalassemia, especially anemia and muscle damage as the main manifestations, has not been reported. Administration of levothyroxine sodium is effective in correcting anemia in patients with CH and alpha thalassemia. LESSON: Due to CH and alpha thalassemia, there are no specific symptoms and they are prone to missed diagnosis and misdiagnosis. Therefore, patients with anemia and elevated muscle enzyme levels should be routinely tested for thyroid function to diagnose them early and provide proper treatment to avoid negative consequences.
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Anemia , Hipotireoidismo Congênito , Tiroxina , Talassemia alfa , Humanos , Feminino , Talassemia alfa/complicações , Talassemia alfa/diagnóstico , Hipotireoidismo Congênito/complicações , Hipotireoidismo Congênito/diagnóstico , Hipotireoidismo Congênito/tratamento farmacológico , Pré-Escolar , Tiroxina/uso terapêutico , Anemia/etiologia , Anemia/tratamento farmacológico , Doenças Musculares/etiologia , Doenças Musculares/diagnóstico , Doenças Musculares/complicaçõesRESUMO
Intrahepatic cholangiocarcinoma (ICC) is the second commonly-seen liver malignancy and one of the most fatal cancers in Taiwan. Survival after diagnosis of ICC remains poor. This study aimed to investigate the survival and prognostic factors in patients with ICC. All patients with newly diagnosed ICC during 2004 to 2018 were identified from a national cancer database and followed until December 2020. Estimates of overall survival (OS) were conducted using the Kaplan-Meier method and Cox proportional hazards model. Hazard ratios with 95% confidence intervals were calculated. Initially, 7940 patients with ICC disease (stage IV: 55.6%, 4418/7940) were eligible for this study. Only 32.3% (2563/7940) patients with ICC underwent liver resection. After Propensity score matching, 969 pairs (N = 1938) of patients were matched and selected (mean age 62.8 ± 11.0 years, 53.1% were male, 29.7% had cirrhosis). The median follow-up time was 80.0 months (range 25-201 months). The 3-, 5-year OS rates were 44.0%, 36.4% in the surgical group and 26.0%, 23.7% in the non-surgical group, respectively. Surgery, young patients (≤ 54 years), small tumor size, no vascular invasion and chemotherapy were associated with better OS in patients with stages I-III disease. Surgery benefit was maximum in stage I disease followed by stage II. In patients with stage IV disease, factors such as surgery, young patients (≤ 64 years), single tumor, and no vascular invasion were associated with better OS. Chemotherapy was insignificantly associated with better OS. Long-term survival in patients with ICC is very poor. Compared to non-surgical patients, surgery conveys approximately 18% and 12% better OS rates at 3-year and 5-year, respectively. Early detection and surgical intervention may improve OS substantially in patients with ICC.
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Neoplasias dos Ductos Biliares , Colangiocarcinoma , Humanos , Colangiocarcinoma/mortalidade , Colangiocarcinoma/patologia , Colangiocarcinoma/cirurgia , Colangiocarcinoma/terapia , Masculino , Feminino , Pessoa de Meia-Idade , Neoplasias dos Ductos Biliares/mortalidade , Neoplasias dos Ductos Biliares/patologia , Neoplasias dos Ductos Biliares/cirurgia , Neoplasias dos Ductos Biliares/terapia , Prognóstico , Idoso , Taiwan/epidemiologia , Taxa de Sobrevida , Estimativa de Kaplan-Meier , Modelos de Riscos Proporcionais , Pontuação de Propensão , Estadiamento de Neoplasias , HepatectomiaRESUMO
BACKGROUND/AIMS: Hepatocellular carcinoma (HCC) is one of the most common malignant tumors and the third leading cause of cancer-related mortality. Extensive literature suggests that long noncoding RNAs play a role in the progression of HCC and hold potential as diagnostic biomarkers for this disease. MATERIALS AND METHODS: We examined the serum levels of HOX antisense intergenic RNA (HOTAIR) in 49 hepatitis patients, 31 liver cirrhosis (LC), and 37 HCC patients using quantitative real-time polymerase chain reaction. Correlations between serum HOTAIR levels and clinical data were evaluated in HCC patients. The receiver operating characteristic curve was utilized to analyze the diagnostic potency of HOTAIR. RESULTS: The HOTAIR levels in serum were significantly higher in HCC patients compared to those with hepatitis (P = .003) and LC patients (P = .048). There was a significant association between the serum levels of HOTAIR and positivity of hepatitis B e antigen (HBeAg) (P = .039) as well as portal vein tumor thrombus (P = .040) in HCC patients. The area under the curve (AUC) for HOTAIR for distinguishing HCC from hepatitis and LC was 0.697. The combined AUC for HOTAIR, HBeAg, and alpha-fetoprotein (AFP) was 0.777. CONCLUSION: Serum HOTAIR functions as a potential diagnostic marker for hepatitis B virus-related HCC. Combining HOTAIR with clinical data and AFP can reinforce the diagnostic precision on HCC.
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Biomarcadores Tumorais , Carcinoma Hepatocelular , Neoplasias Hepáticas , RNA Longo não Codificante , Humanos , Carcinoma Hepatocelular/sangue , Carcinoma Hepatocelular/virologia , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/genética , Neoplasias Hepáticas/sangue , Neoplasias Hepáticas/virologia , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/diagnóstico , RNA Longo não Codificante/sangue , Masculino , Feminino , Pessoa de Meia-Idade , Biomarcadores Tumorais/sangue , Adulto , Cirrose Hepática/sangue , Cirrose Hepática/diagnóstico , Cirrose Hepática/virologia , Cirrose Hepática/genética , Curva ROC , Idoso , Vírus da Hepatite B/genética , Hepatite B Crônica/sangue , Hepatite B Crônica/complicações , Hepatite B Crônica/diagnóstico , Antígenos E da Hepatite B/sangue , Hepatite B/complicações , Hepatite B/sangue , Hepatite B/diagnósticoRESUMO
The aim of this study was to evaluate the accuracy of the JAMR upper-arm blood pressure monitor B23 in the general population according to the AAMI/ESH/ISO Universal Standard (ISO 81060-2â :â 2018/AMD 1â :â 2020). The study recruited participants who met the criteria of the AAMI/ESH/ISO Universal Standard in terms of their number, sex, age, limb size, and blood pressure (BP) distribution. The study involved measuring BP, including both SBP and DBP, using both the test device and a standard mercury sphygmomanometer in sequential measurements. Of 90 participants, 85 qualified participants were analyzed. A total of 255 sets of comparison data (three sets for each subject) were obtained and analyzed. For the validation criterion 1, the meanâ ±â SD of the differences between the JAMR B23 and mercury sphygmomanometer BP readings was -0.24â ±â 6.52/-2.67â ±â 5.6â mmHg (SBP/DBP). For criterion 2, the SD of the averaged BP (SBP/DBP) differences between the JAMR B23 and reference BP (SBP/DBP) per participant was 5.61/5.13â mmHg (the requirement was ≤6.95/6.43â mmHg by calculation). The JAMR B23 passed all the requirements of the AAMI/ESH/ISO Universal Standard (ISO 81060-2â :â 2018/AMD 1â :â 2020) and can be recommended for clinical and self/home use in the general population.
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INTRODUCTION: Frailty in older adults can lead to a gradual decline in organ function. Without timely diagnosis and intervention, this condition can progress rapidly, increasing the risk of disability and mortality. OBJECTIVES: The aim of this project was to implement evidence-based practices for managing frailty in the medical ward to prevent disability in older patients. METHODS: This project was conceptually informed by the JBI Evidence Implementation Framework. This framework uses an audit and feedback approach and a pre- and post-test design to measure baseline compliance, develop implementation strategies responsive to gaps in compliance, and conduct a final evaluation to measure changes in compliance. JBI PACES and JBI GRiP situational analysis software were used to support data collection and implementation planning. Ten audit criteria were used with a sample of 30 patients in a regional teaching hospital in southern Taiwan. RESULTS: The baseline audit showed poor compliance, with rates below 30% for all ten audit criteria. Through strategies such as professional training and education, the implementation of evidence-based care guidelines, and interdisciplinary consensus-building, the follow-up audit revealed an increase in compliance to over 90% for each audit criterion. CONCLUSIONS: Frailty management strategies based on evidence-based audit criteria were implemented and routinely measured. The most effective strategies for improving compliance included the development of a training course, a digitized assessment tool, team meetings, interdisciplinary collaboration, communication, and consensus-building. SPANISH ABSTRACT: http://links.lww.com/IJEBH/A225.
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This study aims to evaluate the trends in rheumatoid arthritis (RA) in China from 1990 to 2021 by analyzing data from the Global Burden of Disease (GBD) 2021 study and to predict the trends for the next 25 years. Age-standardized incidence rates (ASIR) and age-standardized mortality rates (ASMR) were calculated, and the estimated annual percentage change was used to illustrate differences in age distribution among various populations. Age-period-cohort (APC) analysis and Bayesian APC (BAPC) models were employed to forecast the burden of RA in China from 2022 to 2046. From 1990 to 2021, the ASIR of RA in China increased from 11.6 to 13.7, with a significantly higher ASIR in females than in males. Despite the increase in incidence, the ASMR related to RA decreased from 0.7 to 0.5. Predictions using the BAPC model indicate that the incidence of RA will continue to rise, with an expected ASIR of approximately 16.4 by 2046, and the total number of RA cases is projected to reach around 342,000. In terms of mortality, the ASMR is expected to decline to 0.3 by 2046, although the total number of deaths might reach about 40,000. The incidence of RA in China has significantly increased over the past 30 years. Although the incidence rate and the total number of RA cases may continue to rise in the future, the mortality rate of RA has been consistently declining. Key Points ⢠Over the past 30 years, the incidence of RA in China has significantly increased; although the incidence rate and total number of cases may continue to rise, the mortality rate has been consistently declining.
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Artrite Reumatoide , Humanos , Artrite Reumatoide/mortalidade , Artrite Reumatoide/epidemiologia , China/epidemiologia , Incidência , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Idoso , Carga Global da Doença/tendências , Previsões , Distribuição por Idade , Teorema de Bayes , Mortalidade/tendências , Adulto JovemRESUMO
Nicotinamide mononucleotide (NMN) serves as a precursor for NAD+ synthesis and has been shown to have positive effects on the human body. Previous research has predominantly focused on the nicotinamide phosphoribosyltransferase-mediated route (NadV-mediated route) for NMN biosynthesis. In this study, we have explored the de novo NMN biosynthesis route as an alternative pathway to enhance NMN production. Initially, we systematically engineered Escherichia coli to enhance its capacity for NMN synthesis and accumulation, resulting in a remarkable over 100-fold increase in NMN yield. Subsequently, we progressively enhanced the de novo NMN biosynthesis route to further augment NMN production. We screened and identified the crucial role of MazG in catalyzing the enzymatic cleavage of NAD+ to NMN. And the de novo NMN biosynthesis route was optimized and integrated with the NadV-mediated NMN biosynthetic pathways, leading to an intracellular concentration of 844.10 ± 17.40 µM NMN. Furthermore, the introduction of two transporters enhanced the uptake of NAM and the excretion of NMN, resulting in NMN production of 1293.73 ± 61.38 µM. Finally, by engineering an E. coli strain with optimized PRPP synthetase, we achieved the highest NMN production, reaching 3067.98 ± 27.25 µM after 24 h of fermentation at the shake flask level. In addition to constructing an efficient E. coli cell factory for NMN production, our findings provide new insights into understanding the NAD+ salvage pathway and its role in energy metabolism within E. coli.
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Escherichia coli , Engenharia Metabólica , NAD , Mononucleotídeo de Nicotinamida , Escherichia coli/metabolismo , Escherichia coli/genética , Mononucleotídeo de Nicotinamida/metabolismo , Engenharia Metabólica/métodos , NAD/metabolismo , Proteínas de Escherichia coli/metabolismo , Proteínas de Escherichia coli/genética , Nicotinamida Fosforribosiltransferase/metabolismo , Nicotinamida Fosforribosiltransferase/genética , Vias Biossintéticas/genéticaRESUMO
Seed germination and dispersal have an important impact on the establishment and spread of invasive plants. Understanding the extent of intraspecific seed trait variations can enhance our understanding of how invasive plants respond to environmental change after introduction and help predict the dynamic of invasive species under future environmental conditions. However, less attention has been given to the variation in seed traits within species as opposed to among species. We compared seed production, seed morphological traits, dispersal ability, and seedling performance of Chromolaena odorata from 10 introduced populations in Asia and 12 native populations in America in a common garden. The results showed that range (introduced vs. native) and climate affected these traits. Compared with the native population, the introduced populations had higher seed numbers per capitula, lighter seeds, and higher potential dispersal ability seeds (lower terminal velocity) but lower germination rates and seedling lengths. Climatic clines in seed numbers per capitula and pappus length were observed; however, the clines in pappus length differed between the introduced and native populations. Trait covariation patterns were also different between both ranges. In the native populations, there was a trade-off between seed numbers per capitula and seed mass, while this relationship was not found for the introduced populations. These results indicate that C. odorata alters the ecological strategy of seed following invasion, which facilitates its establishment and fast dispersal and contributes to successful invasion in the introduced ranges.
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Headspace-solid phase microextraction/gas chromatography-mass spectrometry (HS-SPME/GC-MS) and electronic nose (E-nose) technologies were implemented to characterize the volatile profile of aerial part from 40 coriander varieties. A total of 207 volatile compounds were identified and quantified, including aldehydes, alcohols, terpenes, hydrocarbons, esters, ketones, acids, furans, phenols and others. E-nose results showed that W5S and W2W were representative sensors responding to coriander odor. Among all varieties, the number (21-30 species) and content (449.94-1050.55 µg/g) of aldehydes were the highest, and the most abundant analytes were (Z)-9-hexadecenal or (E)-2-tetratecenal, which accounted for approximately one-third of the total content. In addition, 37 components were determined the characteristic constituents with odor activity values (OAVs) ≥ 1, mainly presenting citrusy, fatty, soapy and floral smells. Hierarchical cluster analysis (HCA) and principal component analysis (PCA) could effectively distinguish different varieties. This study provided a crucial theoretical basis for flavor evaluation and quality improvement of coriander germplasm resources.
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Coriandrum , Nariz Eletrônico , Cromatografia Gasosa-Espectrometria de Massas , Odorantes , Microextração em Fase Sólida , Compostos Orgânicos Voláteis , Compostos Orgânicos Voláteis/química , Coriandrum/química , Odorantes/análise , QuimiometriaRESUMO
Background: Sarcopenia is a progressive, systemic skeletal muscle disorder. Resistance exercise and physical activity have been proven effective in its treatment, but consensus on pharmacological interventions has not yet been reached in clinical practice. ß-Hydroxy-ß-methylbutyrate (HMB) is a nutritional supplement that has demonstrated favorable effects on muscle protein turnover, potentially contributing to beneficial impacts on sarcopenia. Aim: To assess the potential positive effects of HMB or HMB-containing supplements on individuals with sarcopenia, a systematic review and meta-analysis was conducted. Methods: A systematic review and meta-analysis were conducted on randomized controlled trials (RCTs) examining the treatment of sarcopenia with HMB. Two assessors independently conducted screening, data extraction, and bias risk assessment. Outcome data were synthesized through a random-effects model in meta-analysis, using the mean difference (MD) as the effect measure. Results: A meta-analysis was conducted on six studies. HMB or HMB-rich nutritional supplements showed a statistically significant difference in Hand Grip Strength (HGS) for sarcopenia patients [MD = 1.26, 95%CI (0.41, 2.21), p = 0.004], while there was no statistically significant difference in Gait Speed (GS) [MD = 0.04, 95%CI (-0.01, 0.08), p = 0.09], Fat Mass (FM) [MD = -0.18, 95%CI (-0.38, 0.01), p = 0.07], Fat-Free Mass (FFM) [MD = 0.09, 95%CI (-0.23, 0.42), p = 0.58], and Skeletal Muscle Index (SMI) [MD = 0.01, 95%CI (-0.00, 0.01), p = 0.13]. Conclusion: HMB or HMB-rich nutritional supplements are beneficial for muscle strength in sarcopenia patients. However, there is limited evidence demonstrating significant effects on both muscle strength and physical performance in sarcopenia individuals. HMB may be considered as a treatment option for sarcopenia patients. Systematic review registration: CRD42024512119.
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CRISPR derived base editing techniques tend to edit multiple bases in the targeted region, which impedes precise reversion of disease-associated single nucleotide variations (SNVs). We designed an imperfect gRNA (igRNA) editing strategy to achieve bystander-less single-base editing. To predict the performance and provide ready-to-use igRNAs, we employed a high-throughput method to edit 5000 loci, each with approximate 19 systematically designed ABE igRNAs. Through deep learning of the relationship of editing efficiency, original gRNA sequence and igRNA sequence, AI models were constructed and tested, designated igRNA Prediction and Selection AI models (igRNA-PS). The models have three functions, First, they can identify the major editing site from the bystanders on a gRNA protospacer with a near 90% accuracy. second, a modified single-base editing efficiency (SBE), considering both single-base editing efficiency and product purity, can be predicted for any given igRNAs. Third, for an editing locus, a set of 64 igRNAs derived from a gRNA can be generated, evaluated through igRNA-PS to select for the best performer, and provided to the user. In this work, we overcome one of the most significant obstacles of base editors, and provide a convenient and efficient approach for single-base bystander-less ABE base editing.
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OBJECTIVE: To campare biomechanical effects of different postural compression techniques on three-dimensional model of lumbar disc herniation (LDH) by finite element analysis. METHODS: Lumbar CT image of a 48-year-old female patient with LDH (heighted 163 cm, weighted 53 kg) was collected. Mimics 20.0, Geomagic Studio, Solidwords and other software were used to establish three-dimensional finite element model of LDH on L4,5 segments. Compression techniques under horizontal position, 30° forward bending and 10° backward extension were simulated respectively. After applying the pressure, the effects of compression techniques under different positions on stress, strain and displacement of various tissues of intervertebral disc and nerve root were observed. RESULTS: L4, 5 segment finite element model was successfully established, and the model was validated. When compression manipulation was performed on the horizontal position, 30° flexion and 10° extension, the annular stress were 0.732, 5.929, 1.286 MPa, the nucleus pulposus stress were 0.190, 1.527, 0.295 MPa, and the annular strain were 0.097, 0.922 and 0.424, the strain sizes of nucleus pulposus were 0.153, 1.222 and 0.282, respectively. The overall displacement distance of intervertebral disc on Y direction were -3.707, -18.990, -4.171 mm, and displacement distance of nerve root on Y direction were +7.836, +5.341, +3.859 mm, respectively. The relative displacement distances of nerve root and intervertebral disc on Y direction were 11.543, 24.331 and 8.030 mm, respectively. CONCLUSION: Compression manipulation could make herniated intervertebral disc produce contraction and retraction trend, by increasing the distance between herniated intervertebral disc and nerve root, to reduce symptoms of nerve compression, to achieve purpose of treatment for patients with LDH, in which the compression manipulation is more effective when the forward flexion is 30°.
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Análise de Elementos Finitos , Deslocamento do Disco Intervertebral , Vértebras Lombares , Humanos , Deslocamento do Disco Intervertebral/fisiopatologia , Feminino , Pessoa de Meia-Idade , Vértebras Lombares/fisiopatologia , Postura , Fenômenos Biomecânicos , Imageamento TridimensionalRESUMO
Objective: The meta-analysis aimed to explore the cardiac adaptation in hypothyroidism patients by cardiac magnetic resonance. Research methods and procedures: Databases including PubMed, Cochrane Library, Embase, CNKI, and Sinomed for clinical studies of hypothyroidism on cardiac function changes. Databases were searched from the earliest data to 15 June 2023. Two authors retrieved studies and evaluated their quality. Review Manager 5.4.1 and Stata18 were used to analyze the data. This study is registered with the International Platform of Registered Systematic Review and Meta-analysis Protocols (INPLASY), 202440114. Results: Six studies were selected for further analysis. Five of them reported differences in cardiac function measures between patients with hypothyroidism and healthy controls, and three studies reported cardiac function parameters after treatment in patients with hypothyroidism. The fixed-effect model combined WMD values for left ventricular ejection fraction (LVEF) had a pooled effect size of -1.98 (95% CI -3.50 to -0.44], P=0.01), implying that LVEF was lower in patients with hypothyroidism than in healthy people. Analysis of heterogeneity found moderate heterogeneity (P = 0.08, I² = 50%). WMD values for stroke volume (SV), cardiac index (CI), left ventricular end-diastolic volume index(LVEDVI), left ventricular end-systolic volume (LESVI), and left ventricular mass index(LVMI) were also analyzed, and pooled effect sizes showed the CI and LVEDVI of patients with hypothyroidism ware significantly decrease (WMD=-0.47, 95% CI [-0.93 to -0.00], P=0.05, WMD=-7.99, 95%CI [-14.01 to -1.96], P=0.009, respectively). Patients with hypothyroidism tended to recover cardiac function after treatment [LVEF (WMD = 6.37, 95%CI [2.05, 10.69], P=0.004), SV (WMD = 7.67, 95%CI [1.61, 13.74], P=0.01), CI (WMD = 0.40, 95%CI [0.01, 0.79], P=0.05)], and there was no difference from the healthy controls. Conclusion: Hypothyroidism could affect cardiac function, although this does not cause significant heart failure. It may be an adaptation of the heart to the hypothyroid state. There was a risk that this adaptation may turn into myocardial damage. Cardiac function could be restored after treatment in patients with hypothyroidism. Aggressive levothyroxine replacement therapy should be used to reverse cardiac function. Systematic review registration: https://inplasy.com, identifier (INPLASY202440114).
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Coração , Hipotireoidismo , Humanos , Hipotireoidismo/fisiopatologia , Coração/fisiopatologia , Coração/diagnóstico por imagem , Adaptação Fisiológica/fisiologia , Imageamento por Ressonância Magnética/métodos , Função Ventricular Esquerda/fisiologia , Volume Sistólico/fisiologiaRESUMO
A supercritical carbon dioxide (SCCO2) fluid, characterized by gas-like diffusivity, near-zero surface tension, and excellent mass transfer properties, is used as a precursor to produce silicon oxycarbide (SiOC) coating. SCCO2 disperses and reacts with Si particles to form an interfacial layer consisting of Si, O, and C. After an 850 °C annealing process, a conformal SiOC coating layer forms, resulting in core-shell Si@SiOC particles. High-resolution transmission electron microscopy and its X-ray line-scan spectroscopy, X-ray photoelectron spectroscopy, Fourier-transform infrared spectroscopy, and Raman spectroscopy, are used to examine the SiOC formation mechanism. Effects of SCCO2 interaction time on the SiOC properties are investigated. The SiOC layer connects the Si@SiOC particles, improving electron and Li+ transport. Cyclic voltammetry, galvanostatic intermittent titration technique, and electrochemical impedance spectroscopy are employed to examine the role of SiOC during charging/discharging. Operando X-ray diffraction data reveal that the SiOC coating reduces crystal size of the formed Li15Si4 and increases its formation/elimination reversibility during cycling. The Si@SiOC electrode shows a capacitiy of 2250 mAh g-1 at 0.2 A g-1. After 500 cycles, the capacity retention is 72% with Coulombic efficiency above 99.8%. A full cell consisting of Si@SiOC anode and LiNi0.8Co0.1Mn0.1O2 cathode is constructed, and its performance is evaluated.
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In this study we have identified POLθ-S6K-p62 as a novel druggable regulator of radiation response in prostate cancer. Despite significant advances in delivery, radiotherapy continues to negatively affect treatment outcomes and quality of life due to resistance and late toxic effects to the surrounding normal tissues such as bladder and rectum. It is essential to develop new and effective strategies to achieve better control of tumor. We found that ribosomal protein S6K (RPS6KB1) is elevated in human prostate tumors, and contributes to resistance to radiation. As a downstream effector of mTOR signaling, S6K is known to be involved in growth regulation. However, the impact of S6K signaling on radiation response has not been fully explored. Here we show that loss of S6K led to formation of smaller tumors with less metastatic ability in mice. Mechanistically we found that S6K depletion reduced NFκB and SQSTM1 (p62) reporter activity and DNA polymerase θ (POLθ) that is involved in alternate end-joining repair. We further show that the natural compound berberine interacts with S6K in a in a hitherto unreported novel mode and that pharmacological inhibition of S6K with berberine reduces Polθ and downregulates p62 transcriptional activity via NFκB. Loss of S6K or pre-treatment with berberine improved response to radiation in prostate cancer cells and prevented radiation-mediated resurgence of PSA in animals implanted with prostate cancer cells. Notably, silencing POLQ in S6K overexpressing cells enhanced response to radiation suggesting S6K sensitizes prostate cancer cells to radiation via POLQ. Additionally, inhibition of autophagy with CQ potentiated growth inhibition induced by berberine plus radiation. These observations suggest that pharmacological inhibition of S6K with berberine not only downregulates NFκB/p62 signaling to disrupt autophagic flux but also decreases Polθ. Therefore, combination treatment with radiation and berberine inhibits autophagy and alternate end-joining DNA repair, two processes associated with radioresistance leading to increased radiation sensitivity.
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NF-kappa B , Neoplasias da Próstata , Tolerância a Radiação , Proteína Sequestossoma-1 , Transdução de Sinais , Masculino , Animais , Humanos , Neoplasias da Próstata/radioterapia , Neoplasias da Próstata/patologia , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/genética , Neoplasias da Próstata/tratamento farmacológico , Proteína Sequestossoma-1/metabolismo , Proteína Sequestossoma-1/genética , NF-kappa B/metabolismo , NF-kappa B/genética , Transdução de Sinais/efeitos dos fármacos , Camundongos , Tolerância a Radiação/efeitos dos fármacos , Linhagem Celular Tumoral , DNA Polimerase Dirigida por DNA/genética , DNA Polimerase Dirigida por DNA/metabolismo , Proteínas Quinases S6 Ribossômicas 70-kDa/metabolismo , Proteínas Quinases S6 Ribossômicas 70-kDa/genéticaRESUMO
BACKGROUND: Studies have confirmed that osteoporosis has been considered as one of the complications of diabetes, and the health hazards to patients are more obvious. This study is mainly based on the Taiwan National Health Insurance Database (TNHID). Through the analysis of TNHID, it is shown that the combined treatment of traditional Chinese medicine (TCM) medicine in patients of diabetes with osteoporosis (T2DOP) with lower related risks. METHODS: According to the study design, 3131 patients selected from TNHID who received TCM treatment were matched by 1-fold propensity score according to gender, age, and inclusion date as the control group. Cox proportional hazards analyzes were performed to compare fracture surgery, hospitalization, and all-cause mortality during a mean follow-up from 2000 to 2015. RESULTS: A total of 1055/1469/715 subjects (16.85%/23.46%/11.42%) had fracture surgery/inpatient/all-cause mortality of which 433/624/318 (13.83%/19.93%/10.16%) were in the TCM group) and 622/845/397 (19.87%/26.99%/12.68%) in the control group. Cox proportional hazards regression analysis showed that subjects in the TCM group had lower rates of fracture surgery, inpatient and all-cause mortality (adjusted HR = 0.467; 95% CI = 0.225-0.680, P<0.001; adjusted HR = 0.556; 95% CI = 0.330-0.751, P<0.001; adjusted HR = 0.704; 95% CI = 0.476-0.923, P = 0.012). Kaplan-Meier analysis showed that the cumulative risk of fracture surgery, inpatient and all-cause mortality was significantly different between the case and control groups (all log-rank p<0.001). CONCLUSION: This study provides longitudinal evidence through a cohort study of the value of integrated TCM for T2DOP. More research is needed to fully understand the clinical significance of these results.
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Hospitalização , Medicina Tradicional Chinesa , Osteoporose , Humanos , Feminino , Masculino , Osteoporose/mortalidade , Osteoporose/complicações , Idoso , Hospitalização/estatística & dados numéricos , Pessoa de Meia-Idade , Taiwan/epidemiologia , Fraturas Ósseas/mortalidade , Fraturas Ósseas/cirurgia , Modelos de Riscos Proporcionais , Idoso de 80 Anos ou maisRESUMO
PURPOSE: Thrombocytopenia is among the most common chemotherapy-related hematologic toxicities. We aim to determine the predictors of oxaliplatin chemotherapy-induced thrombocytopenia in patients with gastrointestinal tumors to guide the clinic. METHODS: Clinical data of 750 patients with a malignant gastrointestinal tumor were included as the primary cohort. Basic clinical data, serological indices, and anthropometric indices of these patients were collected. According to the presence or absence of CIT, univariate analysis was performed to identify significant factors for multivariate analysis. In R language software, nomogram was constructed based on the results of multi-factor analysis, and the calibration curve and ROC curve were drawn. RESULTS: Univariate analysis identified 17 factors as closely related to CIT occurrence, namely age, lymph node metastasis (N) stage, metastasis (M) stage, lung metastasis, other site metastasis, chemotherapy regimen, course of treatment, total dose of oxaliplatin, AST, albumin, neutrophils, monocytes, baseline platelets, transferrin, natural killer (NK) cell, phase angle, and SMI (P < 0.10). The binary logistic multivariate regression analysis revealed five independent risk factors for developing CIT (P < 0.05), including the M stage, total dose of oxaliplatin, albumin, baseline thrombocyte count, and NK cell. Based on the results of multivariate logistic regression analysis, R software was used to establish a nomogram model. The calibration curve shows that the combined predictor has good consistency. The area under the ROC curve was 0.877 and the best cut-off value was 0.3579613 (sensitivity, 78.9%; specificity, 81.8%), which showed the better prediction efficiency. CONCLUSION: The total dose of oxaliplatin, M stage, albumin, baseline platelet count, and NK cell was independent risk factors for CIT. The sequentially constructed histogram model had a good predictive effect on the risk of thrombocytopenia caused by oxaliplatin chemotherapy in patients with gastrointestinal malignancies.
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To determine the invasiveness of invasive plants, many studies have compared photosynthetic traits or strategies between invasive and native species. However, few studies have compared the photosynthetic dynamics between invasive and native species during light fluctuations. We compared photosynthetic induction, relaxation dynamics and leaf traits between the invasive species, Tithonia diversifolia and two native species, Clerodendrum bungei and Blumea balsamifera, in full-sun and shady habitats. The photosynthetic dynamics and leaf traits differed among species. T. diversifolia showed a slower induction speed and stomatal opening response but had higher average intrinsic water-use efficiency than the two native species in full-sun habitats. Thus, the slow induction response may be attributed to the longer stomatal length in T. diversifolia. Habitat had a significant effect on photosynthetic dynamics in T. diversifolia and B. balsamifera but not in C. bungei. In shady habitat, T. diversifolia had a faster photosynthetic induction response than in full-sun habitat, leading to a higher average stomatal conductance during photosynthetic induction in T. diversifolia than in the two native species. In contrast, B. balsamifera had a larger stomatal length and slower photosynthetic induction and relaxation response in shady habitat than in full-sun habitat, resulting in higher carbon gain during photosynthetic relaxation. Nevertheless, in both habitats, T. diversifolia had an overall higher carbon gain during light fluctuations than the two native species. Our results indicated that T. diversifolia can adopt more effective response strategies under fluctuating light environments to maximize carbon gain, which may contribute to its successful invasion.
RESUMO
Cystic lesions of the gnathic bones present challenges in differential diagnosis. In recent years, artificial intelligence (AI) represented by deep learning (DL) has rapidly developed and emerged in the field of dental and maxillofacial radiology (DMFR). Dental radiography provides a rich resource for the study of diagnostic analysis methods for cystic lesions of the jaws and has attracted many researchers. The aim of the current study was to investigate the diagnostic performance of DL for cystic lesions of the jaws. Online searches were done on Google Scholar, PubMed, and IEEE Xplore databases, up to September 2023, with subsequent manual screening for confirmation. The initial search yielded 1862 titles, and 44 studies were ultimately included. All studies used DL methods or tools for the identification of a variable number of maxillofacial cysts. The performance of algorithms with different models varies. Although most of the reviewed studies demonstrated that DL methods have better discriminative performance than clinicians, further development is still needed before routine clinical implementation due to several challenges and limitations such as lack of model interpretability, multicentre data validation, etc. Considering the current limitations and challenges, future studies for the differential diagnosis of cystic lesions of the jaws should follow actual clinical diagnostic scenarios to coordinate study design and enhance the impact of AI in the diagnosis of oral and maxillofacial diseases.