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BACKGROUND: DNA methylation is one of the most promising biomarkers in predicting the prognosis of colorectal cancer (CRC). We aimed to develop a DNA methylation biomarker that could evaluate the prognosis of CRC. METHODS: A promising DNA methylation biomarker was developed by hypermethylated genes in cancer tissue that were identified from Illumina EPIC methylation arrays. A cohort comprising 30 pairs of snap-frozen tumor tissue and adjacent normal tissue was used for correlation analysis between the methylation and expression status of the marker. The other cohort comprising 254 formalin-fixed paraffin-embedded (FFPE) tumor tissue from 254 CRC patients was used for prognosis analysis. RESULTS: Regulating synaptic membrane exocytosis 2 (RIMS2) was hypermethylated and lowly expressed in CRC comparing to adjacent normal tissue. Hypermethylation of RIMS2 in CRC was correlated with less frequent KRAS mutant and high differentiation. RIMS2 promoter methylation showed independent predictive value for survival outcome (P = 0.015, HR 1.992, 95% CI [(1.140-3.48)]), and a combination of RIMS2 methylation with KRAS status could predict prognosis better. CONCLUSIONS: RIMS2 is frequently hypermethylated in CRC, which can silence the expression of RIMS2. RIMS2 methylation is a novel biomarker for predicting the prognosis of CRC.
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Neoplasias Colorretais , Humanos , Estadiamento de Neoplasias , Neoplasias Colorretais/patologia , Proteínas Proto-Oncogênicas p21(ras)/genética , Prognóstico , Metilação de DNA , Carcinogênese/genética , Transformação Celular Neoplásica/genética , Biomarcadores Tumorais/genética , Regulação Neoplásica da Expressão GênicaRESUMO
BACKGROUND: Immune checkpoint inhibitor (ICI) treatment in patients with microsatellite instability-high/mismatch repair deficient (MSI-H/dMMR) tumors holds promise in reshaping organ preservation in rectal cancer. However, the benefits are accompanied by distinctive patterns of response, introducing a dilemma in the response evaluation for clinical decision-making. PATIENTS AND METHODS: Patients with locally advanced rectal cancer with MSI-H/dMMR tumors receiving neoadjuvant ICI (nICI) treatment (n=13) and matched patients receiving neoadjuvant chemoradiotherapy (nCRT; n=13) were included to compare clinical response and histopathologic features. RESULTS: Among the 13 patients receiving nICI treatment, in the final radiologic evaluation prior to surgery (at a median of 103 days after initiation of therapy), progressive disease (n=3), stable disease (n=1), partial response (n=7), and complete response (n=2) were observed. However, these patients were later confirmed as having pathologic complete response, resulting in pseudoprogression and pseudoresidue with incidences of 23.1% (n=3) and 76.9% (n=10), respectively, whereas no pseudoprogression was found in the 13 patients receiving nCRT. We further revealed the histopathologic basis underlying the pseudoprogression and pseudoresidue by discovering the distinctive immune-related regression features after nICI treatment, including fibrogenesis, dense lymphocytes, and plasma cell infiltration. CONCLUSIONS: Pseudoprogression and pseudoresidue were unique and prevalent response patterns in MSI-H/dMMR rectal cancer after nICI treatment. Our findings highlight the importance of developing specific strategies for response evaluation in neoadjuvant immunotherapy to identify patients with a good response in whom sphincter/organ-preserving or watch-and-wait strategies may be considered.
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Neoplasias Colorretais , Neoplasias Retais , Humanos , Inibidores de Checkpoint Imunológico/farmacologia , Inibidores de Checkpoint Imunológico/uso terapêutico , Terapia Neoadjuvante , Neoplasias Retais/terapia , Neoplasias Retais/patologia , Neoplasias Colorretais/tratamento farmacológico , Instabilidade de Microssatélites , Reparo de Erro de Pareamento de DNARESUMO
Replacing the flammable liquid electrolytes with solid ones has been considered to be the most effective way to improve the safety of the lithium batteries. However, the solid electrolytes often suffer from low ionic conductivity and poor rate capability due to their relatively stable molecular/atomic architectures. In this study, we report a composite solid electrolyte, in which polyethylene oxide (PEO) is the matrix and Li6.4La3Zr1.45Ta0.5Mo0.05O12 (LLZTMO) and Li6.4La3Zr1.4Ta0.6O12 (LLZTO) are the fillers. Ta/Mo co-doping can further promote the ion transport capacity in the electrolyte. The synthesized composite electrolytes exhibit high thermal stability (up to 413 °C) and good ionic conductivity (LLZTMO-PEO 2.00 × 10-4 S·cm-1, LLZTO-PEO 1.53 × 10-4 S·cm-1) at 35 °C. Compared with a pure PEO electrolyte, whose ionic conductivity is in the range of 10-7~10-6 S·cm-1, the ionic conductivity of composite solid electrolytes is greatly improved. The full cell assembled with LiFePO4 as the positive electrode exhibits excellent rate performance and good cycling stability, indicating that prepared solid electrolytes have great potential applications in lithium batteries.
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IMPORTANCE: Patients with pathological complete response (pCR) of rectal cancer following neoadjuvant treatment had better oncological outcomes. However, reliable methods for accurately predicting pCR remain limited. OBJECTIVE: To evaluate whether transrectal ultrasound-guided tru-cut biopsy (TRUS-TCB) adds diagnostic value to conventional modalities for predicting pathological complete response in patients with rectal cancer after neoadjuvant treatment. DESIGN, SETTING, AND PARTICIPANTS: This study evaluated data of patients with rectal cancer who were treated with neoadjuvant treatment and reassessed using TRUS-TCB and conventional modalities before surgery. This study is registered with ClinicalTrials.gov. MAIN OUTCOMES AND MEASURES: The primary outcome was accuracy, along with secondary outcomes including sensitivity, specificity, negative predictive value, and positive predictive value in predicting tumour residues. Final surgical pathology was used as reference standard. RESULTS: Between June 2021 and June 2022, a total of 74 patients were enroled, with 63 patients ultimately evaluated. Among them, 17 patients (28%) exhibited a complete pathological response. TRUS-TCB demonstrated an accuracy of 0.71 (95% CI, 0.58-0.82) in predicting tumour residues. The combined use of TRUS-TCB and conventional modalities significantly improved diagnostic accuracy compared to conventional modalities alone (0.75 vs. 0.59, P =0.02). Furthermore, TRUS-TCB correctly reclassified 52% of patients erroneously classified as having a complete clinical response by conventional methods. The occurrence of only one mild adverse event was observed. CONCLUSIONS AND RELEVANCE: TRUS-TCB proves to be a safe and accessible tool for reevaluation with minimal complications. The incorporation of TRUS-TCB alongside conventional methods leads to enhanced diagnostic performance.
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Terapia Neoadjuvante , Neoplasias Retais , Humanos , Neoplasias Retais/patologia , Neoplasias Retais/diagnóstico por imagem , Neoplasias Retais/terapia , Masculino , Feminino , Pessoa de Meia-Idade , Estudos Prospectivos , Idoso , Biópsia Guiada por Imagem/métodos , Adulto , Ultrassonografia de Intervenção , Reto/patologia , Reto/cirurgia , Reto/diagnóstico por imagem , Valor Preditivo dos Testes , Resultado do TratamentoRESUMO
PURPOSES: Outcome prediction for out-of-hospital cardiac arrest (OHCA) is of medical, ethical, and socioeconomic importance. We hypothesized that blood ammonia may reflect tissue hypoxia in OHCA patients and conducted this study to evaluate the prognostic value of ammonia for the return of spontaneous circulation (ROSC). METHODS: This prospective, observational study was conducted in a tertiary university hospital between January 2008 and December 2008. The subjects consisted of OHCA patients who were sent to the emergency department (ED). The primary outcome was ROSC. The prognostic values were calculated for ammonia levels and the partial pressure of ammonia (pNH(3)), and the results were depicted as a receiver operating characteristics curve with an area under the curve. RESULTS: Among 119 patients enrolled in this study, 28 patients (23.5%) achieved ROSC. Ammonia levels and pNH(3) in the non-ROSC group were significantly higher than those in the ROSC group (167.0 µmol/L vs 80.0 µmol/L, P < .05; 2.61 × 10(-5) vs 1.67 × 10(-5) mm Hg, P < .05, respectively). The predictive capacity of area under the curve for ammonia and pNH(3) for non-ROSC was 0.85 (95% confidence interval, 0.75-0.95) and 0.73 (95% confidence interval, 0.61-0.84), respectively. The multivariate analysis confirmed that ammonia and pNH(3) are independent predictors of non-ROSC. The prognostic value of ammonia was better than that of pNH(3). The cutoff level for ammonia of 84 µmol/L was 94.5% sensitive and 75.0% specific for predicting non-ROSC with a diagnostic accuracy of 89.9%. CONCLUSIONS: Hyperammonemia on ED arrival is independently predictive of non-ROSC for OHCA patients. The findings may offer useful information for clinical management.
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Amônia/sangue , Parada Cardíaca Extra-Hospitalar/sangue , Idoso , Idoso de 80 Anos ou mais , Gasometria , Reanimação Cardiopulmonar , Distribuição de Qui-Quadrado , Serviço Hospitalar de Emergência , Feminino , Humanos , Hipóxia/sangue , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Parada Cardíaca Extra-Hospitalar/terapia , Pressão Parcial , Valor Preditivo dos Testes , Prognóstico , Estudos Prospectivos , Curva ROC , Sensibilidade e EspecificidadeRESUMO
BACKGROUND: More than ten randomized clinical trials are being tested to evaluate the efficacy, effectiveness and safety of a fasting-mimicking diet (FMD) combined with different antitumor agents. METHODS: UMI-mRNA sequencing, Cell-cycle analysis, Label retention, metabolomics, Multilabeling et al. were used to explore mechanisms. A tandem mRFP-GFP-tagged LC3B, Annexin-V-FITC Apoptosis, TUNEL, H&E, Ki-67 and animal model was used to search for synergistic drugs. FINDINGS: Here we showed that fasting or FMD retards tumor growth more effectively but does not increase 5-fluorouracil/oxaliplatin (5-FU/OXA) sensitivity to apoptosis in vitro and in vivo. Mechanistically, we demonstrated that CRC cells would switch from an active proliferative to a slow-cycling state during fasting. Furthermore, metabolomics shows cell proliferation was decreased to survive nutrient stress in vivo, as evidenced by a low level of adenosine and deoxyadenosine monophosphate. CRC cells would decrease proliferation to achieve increased survival and relapse after chemotherapy. In addition, these fasting-induced quiescent cells were more prone to develop drug-tolerant persister (DTP) tumor cells postulated to be responsible for cancer relapse and metastasis. Then, UMI-mRNA sequencing uncovered the ferroptosis pathway as the pathway most influenced by fasting. Combining fasting with ferroptosis inducer treatment leads to tumor inhibition and eradication of quiescent cells by boosting autophagy. INTERPRETATION: Our results suggest that ferroptosis could improve the antitumor activity of FMD + chemotherapy and highlight a potential therapeutic opportunity to avoid DTP cells-driven tumor relapse and therapy failure. FUNDING: A full list of funding bodies can be found in the Acknowledgements section.
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Antineoplásicos , Neoplasias Colorretais , Ferroptose , Animais , Recidiva Local de Neoplasia/tratamento farmacológico , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Oxaliplatina/farmacologia , Fluoruracila/farmacologia , Fluoruracila/uso terapêutico , Apoptose , Jejum , Linhagem Celular Tumoral , RNA Mensageiro/uso terapêutico , Neoplasias Colorretais/patologiaRESUMO
Antibiotic compounds have caused serious environmental concerns. In this study, we developed an effective technology for treatment of chlortetracycline (CTC), a widely used antibiotic compound. A natural heteroatom-doped spent tea leaves-based biochar (STLB) with excellent adsorption and catalytic property was prepared by simple thermal treatment. An adsorption-promoted persulfate-based advanced oxidation process (PS-AOP) using STLB was studied for CTC removal. The results showed that the as-prepared STLB presented favorable adsorption affinity towards CTC with the maximum adsorption capacity of 627 mg g-1. Meanwhile, CTC enriched on the surface of STLB was good for in-situ decomposition of CTC and nearly 97.4 % of CTC was removed within 30 min of pre-adsorption and 60 min of subsequent degradation. The STLB had excellent recyclability and wide pH tolerance range of 3.0-9.0 in combined pre-adsorption and PS-AOP. Reactive oxygen species analysis confirmed that CTC degradation was mainly due to non-radical (singlet oxygen, 1O2) and radicals (SO4- and OH). This study suggests that STLB is a promising adsorption-enhanced PS activator for the treatment of refractory wastewater and also provides a strategy of waste control by spent tea leaves.
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Clortetraciclina , Poluentes Químicos da Água , Adsorção , Carvão Vegetal , Folhas de Planta/química , Chá , Água , Poluentes Químicos da Água/análiseRESUMO
BACKGROUND: The impact of chronic kidney disease (CKD) and hemodialysis on heart function is not fully understood. We aimed to investigate the influence of different stages of CKD and maintenance hemodialysis on heart function. METHODS: One hundred fifty-three patients were categorized into 3 subgroups [56 without CKD as controls; 37 with moderate-advanced CKD, stages 3, 4 or 5, and 60 with end-stage renal disease (ESRD) undergoing maintenance hemodialysis]. Left ventricular (LV) function was assessed by conventional echocardiography and 2-dimensional speckle-tracking echocardiography with strain analysis (2D strain analysis). RESULTS: There was no significant difference of gender, age and LV ejection fraction among groups. Compared with controls, global peak systolic longitudinal strain (GS(l)), circumferential strain and strain rate were decreased in the CKD group. Along with the decline of renal function, GS(l) deteriorated. Moreover, compared with moderate-advanced CKD patients, GS(l), circumferential strain and strain rate were better in ESRD group receiving maintenance hemodialysis. CONCLUSIONS: Worsening renal function was associated with a reduction of systolic function, and could be quantified by 2D strain analysis. The hemodialysis patients have better LV systolic function than the moderate-advanced CKD patients.
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Insuficiência Cardíaca/terapia , Ventrículos do Coração/fisiopatologia , Falência Renal Crônica/fisiopatologia , Diálise Renal/métodos , Disfunção Ventricular Esquerda/terapia , Idoso , Cardiologia/métodos , Ecocardiografia/métodos , Feminino , Insuficiência Cardíaca/complicações , Humanos , Falência Renal Crônica/complicações , Testes de Função Renal , Masculino , Pessoa de Meia-Idade , Veia Cava Inferior/patologia , Disfunção Ventricular Esquerda/complicaçõesRESUMO
OBJECTIVE: We conducted this multicenter cohort study to evaluate the current tumor-node-metastasis staging system and treatment modality by analyzing the survival outcomes of patient groups with stage III and IV colon cancer. PATIENTS AND METHODS: Stage III and IV colon cancer patients from the Surveillance, Epidemiology, and End Results (SEER) database (SEER cohort) and prospectively maintained Sun Yat-sen University (SYSU) cohort were included in this study. Kaplan-Meier method was used to estimate the cumulative rate of overall survival (OS) between patient groups, and the inverse probability weighting method was used to calculated age and sex-adjusted survival curves. The Cox regression model was used to identify the risk factors for OS. RESULTS: A total of 17,911 and 1135 stage III-IV cases were included in the SEER and SYSU cohorts, respectively. Among them, 1448 and 124 resectable stage IV cases underwent curative-intent treatment in the SEER and SYSU cohorts, respectively. The T4N2b group showed a significantly worse survival outcome compared with the M1a subset receiving curative-intent treatment (HR, 1.46; p < 0.001). This finding was validated in the SYSU cohort, in which the T4N2 group had a worse outcome than that of the M1 group receiving curative-intent treatment (HR, 2.44; p < 0.001). These findings were confirmed in the adjusted survival analysis. In the multivariate analysis, the right-side tumor, poor-undifferentiated tumor, and age over 60 years were identified as independent risk factors for T4N2b patients. Based on this multivariate model, the high-risk T4N2b subgroup had a worse survival outcome compared with resectable M1b patients (HR, 1.24; p = 0.03). CONCLUSION: By comparing stage III with stage IV colon cancer patients, we identified a subgroup of stage III patients at a higher risk of death than more advanced stages, implying that current cancer care modalities are not sufficient for these high-risk substages.
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Neoplasias do Colo/terapia , Idoso , Indicadores de Doenças Crônicas , Estudos de Coortes , Neoplasias do Colo/mortalidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Análise de SobrevidaRESUMO
Coexistence of hypertension and diabetes mellitus (DM) increases the risk of cardiovascular disease. However, factors associated with future development of DM have not been well elucidated in patients already having essential hypertension. This study prospectively included 168 patients (mean age 41 +/- 7 years, 112 men) with essential hypertension. All patients did not have DM and vascular or renal complications initially. Baseline demographic data, blood pressure, body mass index, and antihypertensive agents were carefully evaluated and serum high-sensitivity C-reactive protein (hsCRP) was measured at the beginning of the study. All of the patients were followed for at least 6 months. The study endpoint was occurrence of new DM. After a mean follow-up period of 32 +/- 10 months, 22 subjects (13.1%) developed new DM. Patients with new DM had higher baseline glucose (105.2 +/- 11.8 vs 94.2 +/- 8.0 mg/dl, P < 0.001), triglyceride level (213.7 +/- 112.4 vs 155.6 +/- 83.2 mg/dl, P = 0.04), log hsCRP (0.31 +/- 0.44 vs 0.19 +/- 0.25 mg/dl, P = 0.016), and lower high-density lipoprotein (40.2 +/- 7.8 vs 46.6 +/- 14.4 mg/dl, P = 0.045). Total cholesterol, low-density lipoprotein, homeostasis model assessment index, and adiponectin were not different in patients with or without new DM. Among antihypertensive agents, only use of beta-blocker was significantly associated with new DM (P = 0.008). Multivariate Cox regression analysis showed log hsCRP (hazard ratio [HR] 9.77, 95% confidence interval [CI] 2.97-32.10, P < 0.001), age (HR 1.21, 95% CI 1.06-1.38, P = 0.004), and baseline glucose level (HR 1.11, 95% CI 1.06-1.15, P < 0.001) to be independent predictors for occurrence of new DM. High-sensitivity CRP was an independent factor for future development of DM in essential hypertensive patients. Increased inflammation might have a key role in the pathogenesis of DM in hypertension.
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Proteína C-Reativa/metabolismo , Diabetes Mellitus/etiologia , Hipertensão/complicações , Antagonistas Adrenérgicos beta/uso terapêutico , Adulto , Anti-Hipertensivos/uso terapêutico , Biomarcadores/sangue , Glicemia/metabolismo , Colesterol/sangue , LDL-Colesterol/sangue , Diabetes Mellitus/sangue , Diabetes Mellitus/mortalidade , Intervalo Livre de Doença , Feminino , Humanos , Hipertensão/sangue , Hipertensão/tratamento farmacológico , Hipertensão/mortalidade , Estimativa de Kaplan-Meier , Modelos Lineares , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Prognóstico , Modelos de Riscos Proporcionais , Estudos Prospectivos , Medição de Risco , Fatores de Risco , Taiwan , Fatores de Tempo , Triglicerídeos/sangueRESUMO
Increased arterial stiffness is an important marker for target organ damage in essential hypertension. Both serum uric acid (UA) and C-reactive protein (CRP) were reported to be associated with target organ damage. However, the influences of UA and CRP on large arterial stiffness were not well elucidated. This study included 200 essential hypertension patients (64 women) whose age was between 20 and 50 years old (mean age 41 +/- 8 years). None of the patients had diabetes mellitus or overt end-organ damage. Arterial stiffness was assessed by pulse-wave velocity (PWV) measured by tonometry from carotid to radial artery. Serum UA, high-sensitivity CRP (hsCRP), glucose, insulin, and lipid profiles were measured at the same time in each patient. PWV levels were significantly correlated with mean blood pressure (r = 0.245, P < 0.001), diastolic blood pressure (r = 0.323, P < 0.001), high-density lipoprotein (r = -0.169, P = 0.016), and UA (r = 0.234, P = 0.001), but not age, body mass index, blood sugar, insulin, low-density lipoprotein, triglyceride, and hsCRP. Pulse-wave velocity levels were significantly higher in males (8.9 +/- 1.2 vs 8.2 +/- 1.2 m/s, P < 0.001) and smokers (9.3 +/- 1.1 vs 8.5 +/- 1.2 m/s, P < 0.001). Uric acid was significantly correlated with hsCRP (r = 0.294, P < 0.001). After multivariate analysis controlling for all possible confounding factors, UA (odds ratio 1.28, 95% confidence interval 1.02-1.61, P = 0.032) was still independently associated with increased PWV. In conclusion, UA but not hsCRP was independently associated with increased PWV in essential hypertension. Although UA was correlated with hsCRP, the association between UA and PWV was not through the effect of enhanced inflammation.
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Artérias Carótidas/fisiopatologia , Hipertensão/complicações , Doenças Vasculares Periféricas/etiologia , Artéria Radial/fisiopatologia , Ácido Úrico/sangue , Adulto , Biomarcadores/sangue , Pressão Sanguínea , Proteína C-Reativa/análise , Estudos Transversais , Elasticidade , Feminino , Humanos , Hipertensão/sangue , Hipertensão/fisiopatologia , Modelos Logísticos , Masculino , Manometria , Pessoa de Meia-Idade , Razão de Chances , Doenças Vasculares Periféricas/sangue , Doenças Vasculares Periféricas/fisiopatologia , Fluxo Pulsátil , Medição de Risco , Fatores de Risco , Adulto JovemRESUMO
BACKGROUND: We hypothesized that contraction of the LA wall could be documented by speckle tracking and could be applied for assessment of LA function. This study tried to identify the association between LA longitudinal strain (LAS) and strain rate (LASR) measured by speckle tracking with paroxysmal atrial fibrillation (PAF). METHODS: Fifty-two patients (61 +/- 17 years old, 23 men) with sinus rhythm at baseline referred for the evaluation of episodic palpitation were included. Standard four-chamber and two-chamber views were acquired and analyzed off-line. Peak LAS and LASR were carefully identified as the peak negative inflection of speckle tracking waves after P-wave gated by electrocardiography. RESULTS: Ten patients (19%) had PAF. LAS, LASR, age, left ventricular end-diastolic dimension, left ventricular mass, LA volume, and mitral early filling-to-annulus early velocity ratio were different between patients with and without PAF. After multivariate analysis, LASR was significantly independently associated with PAF (OR 8.56, 95% CI 1.14-64.02, P = 0.036). CONCLUSION: Speckle tracking echocardiography could be used in measurements of LAS and LASR. Decreased negative LASR was independently associated with PAF.
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Fibrilação Atrial/diagnóstico por imagem , Ecocardiografia/métodos , Técnicas de Imagem por Elasticidade/métodos , Átrios do Coração/diagnóstico por imagem , Interpretação de Imagem Assistida por Computador/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Estatística como AssuntoRESUMO
INTRODUCTION: Right-sided native endocarditis is a difficult case with fewer cardiac symptoms and fewer classic signs of cutaneous vascular lesions compared with left-sided endocarditis. PATIENT CONCERNS: A 68-year-old Taiwanese man with a history of gouty arthritis, hyperlipidemia, and adrenal insufficiency presented to our ED and complained dyspnea and low back pain for 1 month. DIAGNOSIS ASSESSMENT: The PE showed bilateral crackles on chest auscultation and a palpable fluctuant mass over the anterior chest wall. The chest and abdominal CT scan showed multiple abscess formations involving pulmonary, sternal, and paraspinal areas. The TEE being performed and an oscillating mass over the anterior and septal leaflets of the tricuspid valve and moderate tricuspid regurgitation. INTERVENTIONS: Only pharmacologic treatment without surgical interventions. OUTCOMES: Deceased, patient expired on day 4 after ED visit. CONCLUSION: This case arose as a sequela of staphylococcal endocarditis associated with persistent bacteremia and immunological dysregulation. The diagnosis of right-sided endocarditis is easily missing, multidisciplinary approach should be triggered as soon as possible, which might lead to a better outcome. Right-sided IE is still an important public health issue in southern Taiwan.
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Abscesso/diagnóstico por imagem , Endocardite Bacteriana/diagnóstico , Valva Tricúspide/diagnóstico por imagem , Abscesso/etiologia , Idoso , Ecocardiografia Transesofagiana , Evolução Fatal , Humanos , Masculino , TaiwanRESUMO
OBJECTIVE: The serum concentration of procollagen type I carboxyterminal propeptide (PICP) is a good marker for collagen deposition in hypertension. Increased collagen deposition was associated with myocardial fibrosis and increased arterial stiffness. A decreased adiponectin level is associated with increased atherosclerosis. The role of adiponectin and its relation to PICP in essential hypertension have rarely been studied before. METHODS: We recruited 188 non-diabetic uncomplicated hypertensive patients (mean age: 41+/-7 years; 128 men). No patient had vascular complications or renal or liver diseases. Overnight fasting blood samples were collected to assess patient lipid profiles, blood sugar, insulin, high-sensitivity C-reactive protein (hsCRP), PICP and adiponectin. Carotid to radial pulse wave velocity (PWV) measured using tonometry was used as an index of arterial stiffness. RESULTS: Adiponectin (r = -0.216, p = 0.003) and male gender (p<0.001) were independent determinants of PICP. Diastolic blood pressure (r = 0.422, p<0.001) and current smoking (p = 0.005) were independent determinants of PWV. PWV was significantly correlated with PICP (r = 0.156, p = 0.034). Adiponectin was significantly correlated with triglyceride (r = -0.276, p<0.001), high-density lipoprotein (r = 0.262, p<0.001), the homeostasis model assessment (HOMA) index (r = -0.220, p = 0.002), hsCRP (r = -0.207, p = 0.004) and the body mass index (BMI) (r = -0.202, p = 0.005). After compensation with possible confounding factors, adiponectin was still significantly correlated with PICP (beta = -0.196, p = 0.006). CONCLUSION: Serum adiponectin may be a marker for metabolic syndrome in essential hypertension. Adiponectin was significantly negatively correlated with PICP. Metabolic syndrome probably plays an important role in increased collagen synthesis and arterial stiffness through the effects of decreased adiponectin in non-diabetic essential hypertension.
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Adiponectina/sangue , Anti-Hipertensivos/uso terapêutico , Biomarcadores/sangue , Hipertensão/sangue , Fragmentos de Peptídeos/sangue , Pró-Colágeno/sangue , Adulto , Artérias/fisiopatologia , Velocidade do Fluxo Sanguíneo , Glicemia/metabolismo , Índice de Massa Corporal , Proteína C-Reativa/metabolismo , HDL-Colesterol/sangue , Diástole/efeitos dos fármacos , Elasticidade , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Insulina/sangue , Resistência à Insulina , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Pacientes Ambulatoriais , Fluxo Pulsátil , Fatores de Risco , Fatores Sexuais , Fumar/efeitos adversos , Triglicerídeos/sangueRESUMO
Implant-associated infections in orthopaedic surgeries are very critical as they may hinder bone healing, cause implant failure and even progress to osteomyelitis. Drug-eluting implants for local delivery of antibiotics at surgical sites are thought to be promising in preventing infections. Herein, the antibiotic vancomycin was encapsulated in a poly(ethylene glycol) (PEG)-based hydrogel film that was covalently bound to Ti implants and subsequently covered by a PEG-poly(lactic-co-caprolactone) (PEG-PLC) membrane. Additionally, crosslinked starch (CSt) was mixed with the hydrogel because its porous microstructure is able to inhibit hydrogel swelling and thus slow down drug release. The release behavior could be regulated by the drug loading and the coating thickness. The vancomycin-loaded Ti implants showed no initial burst release, offering a sustained drug release for nearly 3 weeks in vitro and more than 4 weeks in vivo. In a rabbit model of S. aureus infection, the implants with a 4 mg vancomycin loading significantly reduced the inflammatory reaction and exhibited a good antimicrobial capability. The immobilization of the antibiotic-loaded polymeric coatings on orthopaedic implants can offer a sustainable drug release with no initial burst release and maintain an effective concentration for a longer time, so it is expected to be an effective strategy to treat and prevent local bone infections.
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Antibacterianos/química , Portadores de Fármacos/química , Polietilenoglicóis/química , Próteses e Implantes/efeitos adversos , Infecções Relacionadas à Prótese/prevenção & controle , Titânio/química , Vancomicina/química , Animais , Antibacterianos/farmacologia , Osso e Ossos/efeitos dos fármacos , Osso e Ossos/microbiologia , Liberação Controlada de Fármacos , Articulações/efeitos dos fármacos , Articulações/microbiologia , Cinética , Masculino , Coelhos , Amido/química , Vancomicina/farmacologiaRESUMO
BACKGROUND: Left ventricular early diastolic fillings can be reduced by inspiration. However, the effects of left ventricular hypertrophy on such changes have not been studied before. This study was undertaken to investigate whether respiratory changes in transmitral Doppler flow were affected by left ventricular hypertrophy in hypertension patients. METHODS: Eighty-three patients (mean age 46 +/- 8 years, 49 males) with untreated essential hypertension were included in this study. Transmitral Doppler flow velocity was measured both at end-expiration and end-inspiration. Left ventricular mass was measured by M-mode echocardiography. We divided patients into two groups based on the presence of left ventricular hypertrophy or not. RESULTS: Twenty-one patients were diagnosed to have left ventricular hypertrophy. In patients without left ventricular hypertrophy, the peak early filling velocity decreased significantly (from 74 +/- 15 to 71 +/- 18 cm s(-1), P = 0.003), the peak atrial velocity increased significantly (from 65 +/- 17 to 74 +/- 15 cm s(-1), P < 0.001) and the early filling to atrial velocity ratio decreased significantly (from 1.2 +/- 0.3 to 1.1 +/- 0.3, P < 0.001) from end-expiration to end-inspiration. In patients with left ventricular hypertrophy, the parameters of transmitral Doppler flow pattern did not change during respiration. CONCLUSION: Respiratory changes in the transmitral Doppler flow velocity are blunted by left ventricular hypertrophy in hypertension patients. This phenomenon is probably contributed by the increased left ventricular wall stiffness in the left ventricular hypertrophy.
Assuntos
Hipertensão/diagnóstico por imagem , Hipertensão/fisiopatologia , Hipertrofia Ventricular Esquerda/diagnóstico por imagem , Hipertrofia Ventricular Esquerda/fisiopatologia , Valva Mitral/diagnóstico por imagem , Valva Mitral/fisiopatologia , Respiração , Adaptação Fisiológica , Velocidade do Fluxo Sanguíneo , Circulação Coronária , Ecocardiografia Doppler , Feminino , Humanos , Hipertensão/complicações , Hipertrofia Ventricular Esquerda/etiologia , Masculino , Pessoa de Meia-IdadeRESUMO
OBJECTIVE: Postsystolic shortening is associated with hypertensive heart disease, and the degree of postsystolic shortening can be measured by postsystolic strain index (PSI) of the left ventricle (LV) derived from speckle tracking echocardiography. We studied the association between PSI with delayed diastolic lengthening and diastolic dysfunction in hypertension. METHODS: This study recruited 46 patients (mean age 56â±â13 years, 24 men) with untreated hypertension, and 26 normal individuals (mean age 55â±â11 years, 9 men) as controls. Hypertension patients were further divided into two groups based on the presence of diastolic dysfunction. PSI was calculated as [(postsystolic peak longitudinal strainâ-âend-systolic strain)/end-systolic strain]â×â100%. Timing of left-ventricular diastolic lengthening was determined by measurements of time to onset of early diastolic mitral annulus lengthening by tissue Doppler imaging. RESULTS: Total PSI was significantly higher in patients with diastolic dysfunction (252â±â257 vs. 98â±â72%, Pâ=â0.002). After multivariate analysis, PSI was independently associated with diastolic dysfunction in hypertension [every 10% increment of PSI, odds ratio (OR) 1.13, 95% confidence interval (CI) 1.01-1.27, Pâ=â0.036]. PSI was independently correlated with serum procollagen type I carboxyterminal propeptide (betaâ=â0.382, Pâ=â0.028) after multivariable analysis, and time delay from onset of early mitral inflow to onset of early diastolic medial (betaâ=â0.405, Pâ=â0.004) or lateral (betaâ=â0.582, Pâ<â0.001) annulus lengthening. CONCLUSIONS: Increased PSI was associated with increased procollagen type I carboxyterminal propeptide and diastolic dysfunction in hypertension. Postsystolic shortening was associated with delayed diastolic lengthening which contributed to diastolic dysfunction in hypertension.
Assuntos
Ecocardiografia Doppler/métodos , Hipertensão/fisiopatologia , Disfunção Ventricular Esquerda/fisiopatologia , Velocidade do Fluxo Sanguíneo , Diástole/fisiologia , Feminino , Fibrose/complicações , Fibrose/patologia , Ventrículos do Coração/patologia , Ventrículos do Coração/fisiopatologia , Humanos , Hipertensão/complicações , Hipertensão/patologia , Masculino , Pessoa de Meia-Idade , Miocárdio/patologia , Fragmentos de Peptídeos/sangue , Pró-Colágeno/sangue , Sístole/fisiologia , Disfunção Ventricular Esquerda/complicações , Disfunção Ventricular Esquerda/patologiaRESUMO
BACKGROUND: The objective of this study was to investigate myocardial deformation of the left atrium (LA) assessed by two-dimensional speckle tracking echocardiography in patients with permanent atrial fibrillation (AF) and its value for risk stratification for stroke. METHODS: We recruited 66 consecutive patients with permanent AF who were referred to our echocardiography laboratory for evaluation. These patients were divided into two groups according to the presence of previous stroke or not. RESULTS: Peak positive longitudinal strain (LASp) during atrial filling, peak strain rate in the reservoir phase of LA (LASRr), and peak strain rate in the conduit phase (LASRc) were identified from LA strain and strain rate curves. The ratio of peak early filling velocity (E) of mitral inflow to early diastolic annulus velocity (E') of the medial annulus (E/E') was calculated. LASp (10.44% ± 4.2% vs. 15.69% ± 5.1%, P < .001), LASRr (1.09 ± 0.27 1/s vs. 1.37 ± 0.32 1/s, P = .001), and LASRc (-1.28 ± 0.38 1/s vs. -1.62 ± 0.43 1/s, P = .002) were significantly lower in patients with AF with stroke than those without stroke. By multivariate analysis controlling for age, LA volume index, and left ventricular ejection fraction, LASp (OR 0.787, 95% CI, 0.639-0.968, P = .023) and LASRr (OR 0.019, 95% CI, 0.001-0.585, P = .023) were independently associated with stroke but not LASRc, E', and E/E' ratio. CONCLUSION: Decreased LASp and LASRr were independently associated with stroke in patients with permanent AF.
Assuntos
Fibrilação Atrial/patologia , Função do Átrio Esquerdo , Átrios do Coração/patologia , Acidente Vascular Cerebral/patologia , Idoso , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/diagnóstico por imagem , Intervalos de Confiança , Diástole , Feminino , Átrios do Coração/diagnóstico por imagem , Frequência Cardíaca , Humanos , Masculino , Análise Multivariada , Razão de Chances , Prognóstico , Curva ROC , Medição de Risco , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/diagnóstico por imagem , Volume Sistólico , Ultrassonografia , Função Ventricular EsquerdaRESUMO
The templated crosslinked-chitosan microparticles prepared using the imprinting method with the Remazol Black5 (RB5) dye as a template, epichlorohydrin (ECH) as a crosslinker, and sodium hydroxide (NaOH) solution used for the microparticle formation showed the highest adsorption capacity for the RB5 dye compared with those that used other methods with or without a template, three crosslinkers, and two microparticle formations. The results showed that the adsorption of the RB5 dye on the microparticles was affected by the microparticle size, the initial dye concentration, the initial pH value, as well as the temperature. Both kinetics and thermodynamic parameters of the adsorption process were estimated. These data indicated an exothermic spontaneous adsorption process that kinetically followed the second-order adsorption process. Equilibrium experiments fitted well the Langmuir isotherm model, and the maximum monolayer adsorption capacity for the RB5 dye was 2941 mg/g. The competition study showed that the adsorption of the RB5 dye on the microparticles in the mixture solution was much less affected by the existence of the 3R dye than the other way around. Furthermore, the microparticles could be regenerated through the desorption of the dye in pH 10.0 of NaOH solution and could be reused to adsorb the dye again.