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This study synthesized a carboxymethyl chitosan-modified bimetallic Co/Zn-ZIF (CZ@CMC) with strong hydrophilicity and adsorption performance via the one-pot method. Tetracycline hydrochloride (TCH) was used as the model contaminant to evaluate the adsorption and peroxymonosulfate (PMS) activation properties of CZ@CMC. Mechanism showed that the adsorption behavior occurred through pore filling, electrostatic attraction, surface complexation, hydrogen bonding, and π-π stacking. In addition, a CZ@CMC/PMS system was constructed, which had excellent catalytic performance. The hydrophilicity and selective adsorption properties of CMC conferred a greatly accelerated CZ@CMC in catalyzing the PMS process with kobs of 0.095 min-1, in which OH, 1O2, SO4-, O2-, and Co(III) were the main ROS which quenching tests, EPR, and chemical probe experiments verified. In addition, the degradation pathways of TCH were obtained utilizing DFT and HPLC-MS and analyzed to show that the system possessed a good detoxification capacity. This work is expected to provide a green, efficient, and stable strategy to enhance the adsorption properties of catalytic materials and subsequently their co-catalytic properties.
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Quitosano , Cobalto , Estructuras Metalorgánicas , Tetraciclina , Zinc , Quitosano/química , Quitosano/análogos & derivados , Cobalto/química , Tetraciclina/química , Adsorción , Estructuras Metalorgánicas/química , Zinc/química , Catálisis , Contaminantes Químicos del Agua/química , Contaminantes Químicos del Agua/aislamiento & purificación , Purificación del Agua/métodos , Interacciones Hidrofóbicas e Hidrofílicas , PeróxidosRESUMEN
Understanding the changes in carbon structure during the mid-low-temperature pyrolysis of low-rank coal is important for efficient utilization. Raman spectroscopy is commonly used to analyze the structural order of carbonaceous materials, but traditional methods may overlook the heterogeneity of coal/char. This research explores the heterogeneity of char structure derived from low-rank coal at 700 °C through multi-point micro-Raman analysis. The analysis of parameters such as area (A), intensity (I), full width at half maximum (FWHM/W), and peak position (P) reveals that the carbon structure becomes less ordered as coal transforms into char due to the deposition of small molecules on the surface. The study emphasizes the benefits of multi-point detection for gaining in-depth insights into the structural evolution of carbonaceous materials. The increased standard deviation of Raman parameters indicates diverse structural characteristics resulting from pyrolysis at this temperature, which traditional methods may not capture effectively. The mapping method used in this research visually illustrates the distribution of carbon structures in the region.
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BACKGROUND: To investigate the association between cardiovascular risk estimated using the Framingham Risk Score (FRS) and carotid stiffening determined using ultrafast pulse wave velocity (ufPWV) measurements in apparently healthy individuals. METHODS: We enrolled 1034 apparently healthy participants without known cardiovascular disease who underwent ufPWV measurements. Clinical and laboratory findings, carotid intima-media thickness (cIMT), pulse wave velocity at the beginning of systole (PWV-BS), and pulse wave velocity at the end of systole (PWV-ES) were assessed. In FRS assessments based on major cardiovascular risk factors (CVRFs), participants were assigned into three risk categories: low risk (<10%, n = 679), intermediate risk (10-20%, n = 191), and high risk (>20%, n = 164); the low-risk category was further subdivided into three subcategories: < 1% (n = 58), 1%- 5% (n = 374) and > 5% (n = 247). Multivariate logistic regression analyses with crude and adjusted odds ratios (ORs) were used to evaluate the association of carotid stiffening and FRS-based risk stratification. RESULTS: Carotid stiffening indicated by PWV-BS and PWV-ES differed notably between the FRS-estimated low-risk vs. intermediate-risk and high-risk categories, but only PWV-ES differed notably among the low-risk subcategories (all p < 0.010), and correlated notably with the FRS-estimated risk most obviously in low-risk participants (r = 0.517). In participants with cIMT < 0.050 cm, only PWV-ES differed significantly among the FRS-estimated risk categories (all p < 0.001). Increased PWV-BS (adjusted OR: 1.49; p = 0.003) and PWV-ES (adjusted OR: 1.29; p = 0.007) were both associated with FRS categories independent of conventional CVRFs in low- vs. intermediate-risk categories, but not in low- vs. high-risk categories (all p > 0.050). CONCLUSION: In vivo imaging of carotid stiffening by ufPWV measurements is independently linked to FRS categories, and ufPWV indices may help stratify differing levels of cardiovascular risk in apparently healthy young people. AVAILABILITY OF DATA AND MATERIAL: Data generated or analyzed during the study are available from the corresponding author by reasonable request.
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Background: The mortality and disability of chronic kidney disease (CKD) are highly linked to the incidence of atherosclerotic cardiovascular events. Numerous clinical biochemical indicators of renal function often only increase in advanced stages of CKD, driving an urgent need for reliable indicators of atherosclerosis in early CKD. Ultrafast pulse wave velocity (ufPWV) can evaluate the stiffness of the straight carotid in vivo and quantitatively reflect the degree of early atherosclerosis. However, the use of ufPWV in CKD has not yet been reported. In this study, we aimed to explore the association between carotid stiffness, quantified using ufPWV, and renal function in CKD patients. Methods: This cross-sectional study enrolled a total of 582 participants between March 2017 and May 2022 in the Affiliated Hospital of Nanjing University of Traditional Chinese Medicine. Among those, 205 individuals without a history of CKD and estimated glomerular filtration rate (eGFR) ≥90 mL/min/1.73 m2 were included as controls. According to the Kidney Disease Outcomes Quality Initiative (K/DOQI) expert group of the American Kidney Foundation staging for CKD, 44 stages 1 and 2 CKD patients were included in the early CKD group, whereas 49 stages 3, 4, and 5 CKD patients were included in the advanced CKD group. Clinical and serum parameters, ultrasonic characteristics including carotid intima-media thickness (cIMT), and pulse wave velocity at the beginning of systole (PWV-BS) and pulse wave velocity at the end of systole (PWV-ES) of systole were analyzed. One-way analysis of variance (ANOVA) and least significant difference (LSD) tests were performed to compare cIMT, PWV-BS, and PWV-ES among subgroups in pairs. Pearson's correlation analysis, scatter plots, and subgroups correlation analysis were used to determine the relationships among ultrasound characteristics (cIMT, PWV-BS, PWV-ES), and major cardiovascular risk factors. Results: PWV-BS and PWV-ES for the early and advanced CKD groups were significantly higher than those for controls (all P<0.05). PWV-ES had the greatest correlation with age (r=0.474, P<0.001). PWV-ES had the greatest increase with age in the early CKD group (r=0.698, P<0.001). Conclusions: ufPWV can be used for the quantitative evaluation of carotid stiffness in CKD patients. PWV-ES may be more advantageous in the assessment of carotid atherosclerosis in early CKD patients.
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Neuromorphic computing has shown remarkable capabilities in silicon-based artificial intelligence, which can be optimized by using Mott materials for functional synaptic connections. However, the research efforts focus on two-terminal artificial synapses and envisioned the networks controlled by silicon-based circuits, which is difficult to develop and integrate. Here, we propose a dynamic network with laser-controlled conducting filaments based on electric field-induced local insulator-metal transition of vanadium dioxide. Quantum sensing is used to realize conductivity-sensitive imaging of conducting filament. We find that the location of filament formation is manipulated by focused laser, which is applicable to simulate the dynamical synaptic connections between the neurons. The ability to process signals with both long-term and short-term potentiation is further demonstrated with ~60 times on/off ratio while switching the pathways. This study opens the door to the development of dynamic network structures depending on easily controlled conduction pathways, mimicking the biological nervous systems.
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Intratumoral T-cell dysfunction is a hallmark of pancreatic tumors, and efforts to improve dendritic cell (DC)-mediated T-cell activation may be critical in treating these immune therapy unresponsive tumors. Recent evidence indicates that mechanisms that induce dysfunction of type 1 conventional DCs (cDC1) in pancreatic adenocarcinomas (PDAC) are drivers of the lack of responsiveness to checkpoint immunotherapy. However, the impact of PDAC on systemic type 2 cDC2 development and function has not been well studied. Herein, we report the analysis of 3 cohorts, totaling 106 samples, of human blood and bone marrow (BM) from patients with PDAC for changes in cDCs. We found that circulating cDC2s and their progenitors were significantly decreased in the blood of patients with PDAC, and repressed numbers of cDC2s were associated with poor prognosis. Serum cytokine analyses identified IL6 as significantly elevated in patients with PDAC and negatively correlated with cDC numbers. In vitro, IL6 impaired the differentiation of cDC1s and cDC2s from BM progenitors. Single-cell RNA sequencing analysis of human cDC progenitors in the BM and blood of patients with PDAC showed an upregulation of the IL6/STAT3 pathway and a corresponding impairment of antigen processing and presentation. These results suggested that cDC2s were systemically suppressed by inflammatory cytokines, which was linked to impaired antitumor immunity.
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Interleucina-6 , Neoplasias Pancreáticas , Humanos , Interleucina-6/metabolismo , Neoplasias Pancreáticas/patología , Células Dendríticas , Citocinas/metabolismoRESUMEN
Ethnic medicine has a rich history of application. Because of the large number of ethnic groups, wide geographical distribution, and unique medical systems in China, the research on the human use experience(HUE) of ethnic medicine should combine the characteristics of ethnic medicine, be based on practical experience, and respect folk practice and tradition. The clinical positioning of ethnic medicine should consider three factors, i.e., population region, dominant diseases, and clinical demand. We should consider the development of traditional preparations that meet the needs of ethnic regions and encourage the development of new drugs that can be popularized and used nationwide for the dominant diseases of ethnic medicines. Attention should be paid to the problems such as a large number of customary articles or substitutes of ethnic medicinal materials, the phenomena of foreign bodies with the same name and different names for the same substance, the different standards of medicinal materials, and the poor processing standards. The name, processing method, source, medicinal parts, and dosage of ethnic medicinal materials or decoction pieces should be determined, and resources should be carefully evaluated to ensure the safety of medicinal resources and ecology. The preparation of ethnic medicine is mostly in the form of pills, powder, ointment, etc., with simple processing technology. The problems of low-quality stan-dards of some preparations, different prescriptions with the same name, and inconsistent processing technology should be overcome, and the process route and main process parameters should be clarified to lay the foundation for the subsequent empirical research on HUE. In the collection and analysis of the HUE data of ethnic medicine, the core guiding ideology of "patient-centered" should be established, and the experience data of patients should be collected. The problems of weak links existing in the inheritance of ethnic medicine should be solved, and flexible and diverse methods should be adopted. Meanwhile, on the premise of complying with the requirements of the principles of medical ethics, we should respect the religion, culture, and customs of ethnic areas to obtain the key HUE information of ethnic medicine. On the basis of the patient preference information and differences in regional disease epidemiology, population characteristics, and medical practice, whether the HUE conclusions of ethnic medicine can be extrapolated to patients outside the region is evaluated from the aspects of clinical benefits, risk tolerance, risk acceptance, etc. The HUE research on ethnic medicine is carried out in a clear way to guide the research and development of new ethnic medicines.
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Medicamentos Herbarios Chinos , Medicina Tradicional China , Humanos , China , Estándares de Referencia , Tecnología , Medicamentos Herbarios Chinos/uso terapéuticoRESUMEN
SHR-1222, a novel humanized monoclonal antibody targeting sclerostin, has been shown to induce bone formation and decrease bone resorption at a single dose ranging 50-400 mg in our previous phase 1 trial. This study was a randomized, double-blind, placebo-controlled, dose-escalation phase 1 trial, which further investigated the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and immunogenicity of multiple ascending doses of SHR-1222 in women with postmenopausal osteoporosis (POP). A total of 105 women with POP were enrolled and randomly assigned. Twenty-one received placebo and eighty-four received SHR-1222 sequentially (100 mg QM, n=4; 200 or 300 mg QM, n=20; and 400 or 600 mg Q2M, n=20). The most common adverse events included increased blood parathyroid hormone, increased low-density lipoprotein, increased blood alkaline phosphatase, increased blood cholesterol, back pain, and arthralgia, the majority of which were mild in severity without noticeable safety concerns. Serum SHR-1222 exposure (Cmax,ss and AUC0-tau,ss) increased in a greater than dose-proportional manner. Following multiple doses of SHR-1222, the bone formation markers (terminal propeptide of type I procollagen, bone-specific alkaline phosphatase, and osteocalcin) increased in a dose-dependent manner, whereas the bone resorption marker (ß-C-telopeptide) was downregulated. Accordingly, BMD gains in the lumbar spine, total hip, and femoral neck were observed. The maximum BMD increase from baseline at the lumbar spine was detected in the 300 mg QM cohort (14.6% vs. 0.6% in the placebo group on day 169). Six (6/83; 7.2%) subjects developed anti-SHR-1222 antibodies with no discernible effects on PKs, PDs, and safety. Thus, multiple doses of SHR-1222 showed an acceptable safety profile and dose-dependent plasma exposure in women with POP, and could improve their BMD rapidly and prominently by promoting bone formation and inhibiting bone resorption. These findings further support SHR-1222 as a potential alternative agent for the treatment of POP.
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Resorción Ósea , Osteoporosis Posmenopáusica , Humanos , Femenino , Anticuerpos Monoclonales/efectos adversos , Densidad Ósea , Posmenopausia , Fosfatasa Alcalina , Osteoporosis Posmenopáusica/tratamiento farmacológico , Resorción Ósea/inducido químicamenteRESUMEN
BACKGROUND: Popular demand for minimally invasive soft tissue tightening is continuously on the rise. In recent years, subcutaneous radiofrequency or radiofrequency-assisted liposuction (RFAL) has been reported to produce the desired surgical outcome on lower-face and body tightening. However, few studies are found using subcutaneous radiofrequency for midface rejuvenation. AIMS: This study was performed to review our surgical method for the midface rejuvenation using subcutaneous radiofrequency combined with liposuction and to evaluate the clinical outcomes. PATIENTS/METHODS: This retrospective observational study involved 31 patients with mild-to-moderate mid-face laxity. All patients received liposuction combined with subcutaneous radiofrequency on midface from June 2020 to June 2022. Clinical results were assessed objectively using photographs and subjectively by a patient satisfaction survey. RESULTS: All patients recovered well without major complications. High patient satisfaction was attained. The mean score of midface laxity (GGS) as evaluated by jury decreased from 3.3 preoperatively to 1.6 postoperatively. CONCLUSIONS: Our midface tightening technique is safe and effective for patients with a mild-to-moderate midface aging appearance. LEVEL OF EVIDENCE: Therapeutic IV.
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Lipectomía , Envejecimiento de la Piel , Humanos , Lipectomía/efectos adversos , Lipectomía/métodos , Rejuvenecimiento , Cara/cirugía , Tejido Subcutáneo , Satisfacción del PacienteRESUMEN
PURPOSE: The aim of this study was to assess carotid stiffening in a pre-hypertensive (PHT) population using ultrafast pulse wave velocity (ufPWV). METHODS: This study retrospectively enrolled 626 individuals who underwent clinical interviews, serum tests, and assessments of the systolic blood pressure (SBP), diastolic blood pressure (DBP), carotid intima-media thickness (cIMT), pulse wave velocity-beginning of systole (PWV-BS), and pulse wave velocity-end of systole (PWV-ES) between January 2017 and December 2021. The patients were divided into three groups according to their blood pressure (BP)-normal BP (NBP): SBP <130 mmHg and DBP <80 mmHg (n=215); PHT: 130 mmHg≤SBP<140 mmHg and/or 80 mmHg≤DBP<90 mmHg (n=119); hypertensive (HT): SBP ≥140 mmHg and/or DBP ≥90 mmHg (n=292). Correlation analyses and comparisons were performed among the groups and in the cIMT subgroups (cIMT ≥0.050 cm and <0.050 cm). RESULTS: cIMT and PWV-ES significantly differed among the BP groups (P<0.05). The BP groups had similar PWV-BS when cIMT <0.050 cm or cIMT ≥0.050 cm (all P>0.05). However, the NBP group had a notably lower PWV-ES than the PHT (P<0.001 and P=0.024) and HT (all P<0.001) groups in both cIMT categories, while the PWV-ES in the PHT group were not significantly lower than in the HT group (all P>0.05). CONCLUSION: Carotid morphological and biomechanical properties in the PHT group differed from those in the NBP group. ufPWV could be used for an early evaluation of carotid stiffening linked to pre-hypertension.
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Objective: This study aimed to evaluate an improved park's technique to create a natural double eyelid and reduce scar formation. Methods: The levator aponeurosis, orbicularis oculi muscle, and dermis were fixed using subcutaneous intermittent sutures, and then the skin and the levator aponeurosis were sutured. Postoperative evaluation included double-eyelid stability, symmetry, double-eyelid curve, scar formation, and patient satisfaction. Results: Between January 2021 and August 2021, a total of 89 patients (178 eyes) underwent double-eyelid blepharoplasty by the same surgeon using this improved technique. The mean follow-up period was 15.5 months (range 10 to 18 months). Seventy-six patients were very satisfied with this surgical method, six patients were rather satisfied, and seven patients were dissatisfied. The overall satisfaction rate was 92.1%. Conclusion: This new blepharoplasty method generates a stable, natural double-eyelid line with minimal scarring.
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Blefaroplastia , Cicatriz , Humanos , Cicatriz/prevención & control , Cicatriz/cirugía , Párpados/cirugía , Blefaroplastia/métodos , Satisfacción del Paciente , Piel , Estudios RetrospectivosRESUMEN
Tibetan medicine is an essential part of Chinese medicine and has unique theoretical experience and therapeutic advantages. According to the development principle of inheriting the essence, sticking to the truth, and keeping innovative, the supervision department should give clear and reasonable guidance considering the characteristics of Tibetan medicine, establish a standard system for quality control, clinical verification and evaluation, and accelerate the research and commercialization of new drugs. In view of the needs of drug supply-side reform and the current situation of Tibetan medicine and new pharmaceutical research, we ponder and provide suggestions on the confusion faced by the current supervision of Tibetan drug registration, hoping to contribute to the supervision strategy of Tibetan drug registration and the high-quality development of Tibetan medicine industry.
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Medicina Tradicional Tibetana , Investigación Farmacéutica , Tibet , Control de Calidad , Industria FarmacéuticaRESUMEN
Human use experience(HUE) is important for the research and development of Chinese medicine. For the sake of more reliable data, the Professional Committee for Clinical Evaluation of Chinese Medicine of Chinese Pharmaceutical Association drafted the Expert Consensus on Human Use Experience Research of Traditional Chinese Medicine. It highlights that the research on HUE should have clear purposes, describe the theoretical basis of traditional Chinese medicine(TCM) for the clinical indications and prescriptions and the clinical value of prescriptions, especially the advantages or characteristics in clinical orientation and target population, evaluate the dosages and number of medicinals of prescriptions, verify the accordance with the preparation process of new Chinese medicine, analyze feasibility of the process for large-scale production and the rationality of the dosage form, and assess the medicinal material resources. Moreover, such research should have reasonable protocol and the collection of clinical data on HUE must comply with medical ethics and avoid conflicts of interest. The collection method should be selected depending on the characteristics of clinical data. Quality control measures should be formulated to ensure the authenticity, accuracy, completeness, reliability, and traceability of clinical data. The definitions on the clinical data should be uniform and clear, and methods should be adopted to avoid bias. The data can be statistically analyzed after the processing. Through the study of HUE, the clinical orientation, target population, commonly used dosage, course of treatment, preliminary efficacy and safety of Chinese medicine prescriptions will be clarified. On this basis, the data on the HUE should be discussed and conclusions will be drawn. Finally, a standardized report will be formed.
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Medicamentos Herbarios Chinos , Medicina Tradicional China , Consenso , Prescripciones de Medicamentos , Medicamentos Herbarios Chinos/uso terapéutico , Humanos , Reproducibilidad de los ResultadosRESUMEN
The coal tends to be affected by the water vapor from quenching coke process in the pyrolysis process during the coal carbonization process and in turn causes the variation of physicochemical properties of semicoke. The preparation of semicoke based on different pyrolysis temperatures and water vapor content was carried out in order to investigate the influence of water vaper on physicochemical properties of the pyrolytic semicoke, combined with specific surface area analysis and thermal analysis to study the pore structure and combustion properties of semicoke. The morphology of the semicoke and the alteration rule of carbon-containing functional groups were analyzed by scanning electron microscopy and X-ray photoelectron spectroscopy. The result indicates that adding an appropriate amount of water vapor (40%) instead of excess (60%) in the pyrolysis process (800 °C) is beneficial to the increase of the proportion of fixed carbon and the removal of volatile and ash. The specific surface area and the combustion performance of the semicoke is significantly improved when the appropriate amount of water vapor was added. The water vapor content has a slight effect on surface functional groups when the temperature ranges from 500 to 700 °C, whereas the higher water vapor content inhibits the improvement of physicochemical properties of the semicoke when the pyrolysis temperature is higher (800 °C). Therefore, the entry of excess water vapor (60%) into the high-temperature pyrolysis section should be avoided in the process of quenching coke or it would have an adverse impact on the performance of semicoke.
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PURPOSE: The present study investigated the association between Systematic COronary Risk Evaluation (SCORE)-estimated cardiovascular risk and carotid stiffening in a middle-aged population using ultrafast pulse wave velocity (ufPWV). METHODS: This study enrolled 683 participants without known cardiovascular disease or diabetes mellitus who underwent ufPWV measurements. Clinical interviews, physical examinations, laboratory findings, carotid intima-media thickness (cIMT), pulse wave velocity (PWV) at the beginning of systole (PWV-BS), and PWV at the end of systole (PWV-ES) were assessed. Each participant underwent an assessment of SCORE risk based on major cardiovascular risk factors (CVRFs), including age, sex, smoking, systolic blood pressure (SBP), and total cholesterol (TC). Crude and adjusted odds ratios (ORs) with 95% confidence intervals and ordinal logistic regression were used. Overall CVRFs were adjusted to assess ORs. RESULTS: cIMT and carotid stiffening in PWV-BS and PWV-ES were significantly different between sex subgroups (all P<0.05), but only PWV-ES increased gradually in age and SCORE-estimated risk subgroups (all P<0.05). Compared with cIMT (r=0.388, P<0.001) and PWV-BS (r=0.159, P<0.001), PWV-ES was more strongly correlated with SCORE categories (r=0.405, P<0.001). Higher PWV-ES values were associated with SCORE categories independently of sex, SBP, TC, and smoking in moderate-risk and high-risk subgroups (OR, 1.63; P<0.001 and OR, 2.12; P=0.024, respectively), but were not independent of age in all risk subgroups (all P>0.05). CONCLUSION: Carotid stiffening quantified by ufPWV is linked to SCORE categories, and elevated PWV-ES may aid in cardiovascular risk stratification.
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To establish and preliminarily validate an individualized reference of carotid stiffness quantified by ultrafast pulse wave velocity (ufPWV), our study included 225 healthy individuals in the modeling cohort and 628 individuals in the validation cohort. All participants underwent assessment of carotid intima-media thickness (cIMT), pulse wave velocity-beginning of systole and pulse wave velocity-end of systole (PWV-ES). A threshold equation of estimated PWV-ES was obtained by multiple linear regression analysis in the modeling cohort as follows: estimated PWV-ES (m/s) = 0.080 × age (y) + 0.767 × low-density lipoprotein (mmol/L) + 0.040 × systolic blood pressure (mm Hg) + 0.372 × sex (male = 1, female = 0) - 2.803. With this equation, the validation cohort was divided into the low PWV-ES (actual PWV-ES ≤ estimated PWV-ES) and high PWV-ES (actual PWV-ES > estimated PWV-ES) groups. A clear boundary was found to be present between the low PWV-ES and high PWV-ES groups in the validation cohort. Participants with increasing PWV-ES increased with age gradually. We further subdivided participants into cIMT subgroups using a cutoff thickness of 0.050 cm. Diagnostic performance analysis revealed that the sensitivity and specificity of the threshold equation were 78.9% and 73.9%, respectively. We established and validated a novel individualized reference equation for estimated PWV-ES, which can likely expand the application of prospective ufPWV assessment.
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Arterias Carótidas/diagnóstico por imagen , Grosor Intima-Media Carotídeo , Análisis de la Onda del Pulso , Rigidez Vascular/fisiología , Estudios de Cohortes , Femenino , Humanos , Modelos Lineales , Masculino , Estudios Prospectivos , Sensibilidad y Especificidad , UltrasonografíaRESUMEN
Pulmonary nodules (PNs) shown as persistent or growing ground-glass opacities (GGOs) are usually lung adenocarcinomas or their preinvasive lesions. Tumor mutation burden (TMB) and somatic mutations are important determinants for the choice of strategy in patients with lung cancer during therapy. A total of 93 post-operative patients with 108 malignant PNs were enrolled for analysis (75 cases in the training cohort and 33 cases in the validation cohort). Radiomics features were extracted from preoperative non-contrast computed tomography (CT) images of the entire tumor. Using commercial next generation sequencing, we detected TMB status and somatic mutations of all FFPE samples. Here, 870 quantitative radiomics features were extracted from the segmentations of PNs, and pathological and clinical characteristics were collected from medical records. The LASSO (least absolute shrinkage and selection operator) regression and stepwise logistic regressions were performed to establish the predictive model. For the epidermal growth factor receptor (EGFR) mutation, the AUCs of the clinical model and the integrative model validated by the validation set were 0.6726 (0.4755-0.8697) and 0.7421 (0.5698-0.9144). For the TMB status, the ROCs showed that AUCs of the clinical model and the integrative model validated by the validation set were 0.7808 (0.6231-0.9384) and 0.8462 (0.7132-0.9791). The quantitative radiomics signatures showed potential value in predicting the EGFR mutant and TMB status in GGOs. Moreover, the integrative model provided sufficient information for the selection of therapy and deserves further analysis.
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Real world study(RWS) refers to the process of collecting real world data related to the health of research subjects in the real world environment for pre-set clinical problems and obtaining the status of drug use and potential benefits/risks through analysis. The data are derived from the hospital information system(HIS), medical insurance system, disease registration system, adverse drug reaction monitoring system, etc. Human use experience of traditional Chinese medicine(TCM) is a new concept put forward by experts after summarizing the problems existing in clinical trials of new TCM drugs. The data come partially from the real world, and more importantly, such key elements as the formulated prescriptions of new TCM drugs, principles and methods, and clinical applications should be covered. RWS is mainly used for adverse drug reaction monitoring after marketing, benefit evaluation of listed drugs, decision-making of medical treatment and medical insurance, as well as supervision and approval of special medical devices and special drugs. It is complementary to randomized controlled clinical trials. Human use experience is suitable for the research and development of Chinese medicinal compound preparations and the expansion of functions and indications. There are no special provisions for clinical indications and target population. There exists a sequential relationship between the human use experience and clinical trials. Specifi-cally, the summarization of human use experience provides good support for the design and implementation of clinical trials, which is an important segment in the research and development of new TCM drugs. The correlation between real-world data and research results and their reliability should be ensured in RWS, and the unreality should be avoided. The key to summarizing the human use experience is to identify the clinical orientation, target population, course of treatment, usage and dosage of new TCM drugs, and it should be noted that human use experience does not only mean clinical experience. Experimental clinical trial(PCT), a type of study in the real world, has been commonly employed for the summary of human use experience. RWS and human use experience are different research designs targeting different clinical questions in the research and development of new TCM drugs, which can be flexibly selected depending on the actual situation.
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Medicamentos Herbarios Chinos , Medicina Tradicional China , Medicamentos Herbarios Chinos/efectos adversos , Humanos , Prescripciones , Reproducibilidad de los Resultados , InvestigaciónRESUMEN
Various characterization methods are used to investigate the physical and chemical properties of steel plant flying dust and waste oil sludge, and the combustion characteristics of the mixtures with pulverized coal are studied via thermogravimetric analysis; the catalytic combustion mechanism is also explored. The results show that two types of metallurgical by-products with small particle sizes and developed pores are evenly dispersed in the pulverized coal and are stably combined with it. The additives reduce the ignition temperature and the temperature corresponding to the maximum combustion rate of pulverized coal; simultaneously, they increase the heat released during pulverized coal combustion. During the pyrolysis stage of pulverized coal, the heat generated via organic component combustion in waste oil sludge promotes a cracking reaction and improves the development of the char's micropore. During the char combustion stage, no catalyst deactivation phenomenon occurs under the ratios of inorganic components in the two types of metallurgical dust and sludge. Two additives markedly reduce the activation energy of the combustion reaction.
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BACKGROUND: Breast cancer is one of the most common cancers and the leading cause of death from cancer among women worldwide. The genetic predisposition to breast cancer may be associated with a mutation in particular genes such as gene BRCA1/2. Patients who carry a germline pathogenic mutation in BRCA1/2 genes have a significantly increased risk of developing breast cancer and might benefit from targeted therapy. However, genetic testing is time consuming and costly. This study aims to predict the risk of gBRCA mutation by using the whole-slide pathology features of breast cancer H&E stains and the patients' gBRCA mutation status. METHODS: In this study, we trained a deep convolutional neural network (CNN) of ResNet on whole-slide images (WSIs) to predict the gBRCA mutation in breast cancer. Since the dimensions are too large for slide-based training, we divided WSI into smaller tiles with the original resolution. The tile-based classification was then combined by adding the positive classification result to generate the combined slide-based accuracy. Models were trained based on the annotated tumor location and gBRCA mutation status labeled by a designated breast cancer pathologist. Four models were trained on tiles cropped at 5×, 10×, 20×, and 40× magnification, assuming that low magnification and high magnification may provide different levels of information for classification. RESULTS: A trained model was validated through an external dataset that contains 17 mutants and 47 wilds. In the external validation dataset, AUCs (95% CI) of DL models that used 40×, 20×, 10×, and 5× magnification tiles among all cases were 0.766 (0.763-0.769), 0.763 (0.758-0.769), 0.750 (0.738-0.761), and 0.551 (0.526-0.575), respectively, while the corresponding magnification slides among all cases were 0.774 (0.642-0.905), 0.804 (0.676-0.931), 0.828 (0.691-0.966), and 0.635 (0.471-0.798), respectively. The study also identified the influence of histological grade to the accuracy of the prediction. CONCLUSION: In this paper, the combination of pathology and molecular omics was used to establish the gBRCA mutation risk prediction model, revealing the correlation between the whole-slide histopathological images and gRCA mutation risk. The results indicated that the prediction accuracy is likely to improve as the training data expand. The findings demonstrated that deep CNNs could be used to assist pathologists in the detection of gene mutation in breast cancer.