Dynamic Micelle-Hydrogels for 3D-Architected Transition Metal Sulfides.

Additive manufacturing of transition metal sulfides (TMS) enables the creation of complex 3D structures, significantly expanding their applications. However, preparing 3D-structured TMS remains challenging due to difficulties in developing suitable inks. In this study, a supramolecular micelle hydrogel as the ink to fabricate 3D-structured TMS is utilized. Initially, the hydrogels are printed and infused with metal salt solutions to stabilize the structures, which are then calcined to convert into miniaturized 3D-TMS replicas. The micellar hydrogels crosslink via hydrophobic interactions, with sodium dodecyl sulfonate (SDS) micelles providing both a hydrophobic environment and sulfur sources. During calcination, the decomposed sulfur precursors coordinate with metal ions to form various TMS, including FeS2, Cu2S, Ni3S2, and Co9S8, along with several metal sulfides like PbS and SnS. Additionally, the method also allows for the preparation of transition metal dichalcogenides such as MoS2 and WS2. The formation mechanism is demonstrated using Ni3S2 as an example which exhibits notable catalytic activity in oxygen evolution reactions (OER) and hydrogen evolution reactions (HER). Given its simplicity and versatility, this dynamic micellar hydrogel-derived strategy offers a promising pathway for creating advanced TMS materials.

The first in-human study to evaluate the antiplatelet properties of the clopidogrel conjugate DT-678 in acute coronary syndrome patients and healthy volunteers.

BACKGROUND AND PURPOSE: DT-678 is a novel antiplatelet prodrug, capable of releasing the antiplatelet active metabolite of clopidogrel (AM) upon exposure to glutathione. In this study, we investigated factors responsible for clopidogrel high on-treatment platelet reactivity (HTPR) in acute coronary syndrome (ACS) patients and evaluated the capacity of DT-678 to overcome HTPR. EXPERIMENTAL APPROACH: A total of 300 consecutive ACS patients naive to P2Y12 receptor inhibitors were recruited and genotyped for CYP2C19 alleles. Blood samples were drawn before and after administration of 600-mg clopidogrel. Platelet reactivity index (PRI) and plasma AM concentrations were determined and grouped according to their CYP2C19 genotypes. DT-678 was applied ex vivo to whole blood samples to examine its inhibitory effects. To further examine the antiplatelet effectiveness of DT-678 in vivo, 20 healthy human subjects were recruited in a Phase I clinical trial, and each received a single dose of either 3-mg DT-678 or 75-mg clopidogrel. The pharmacokinetics and pharmacodynamics in different CYP2C19 genotype groups were compared. KEY RESULTS: Statistical analyses revealed that CYP2C19 genotype, body mass index, hyperuricaemia, and baseline PRI were significantly associated with a higher risk of clopidogrel HTPR in ACS patients. The addition of DT-678 ex vivo decreased baseline PRI regardless of CYP2C19 genotypes, overcoming clopidogrel HTPR. This observation was further confirmed in healthy volunteers receiving 3 mg of DT-678. CONCLUSION AND IMPLICATIONS: These results suggest that DT-678 effectively overcomes clopidogrel HTPR resulting from genetic and/or clinical factors in Chinese ACS patients, demonstrating its potential to improve antiplatelet therapy.

Effect of APOE gene on cerebral oxygen saturation, cerebral electrical activity and prognosis after intracerebral hemorrhage.

Cerebral hemorrhage represents a severe neurological disorder with significant implications for patient health. Numerous factors play a crucial role in determining the prognosis of this condition. In recent years, research has highlighted the polymorphism of the apolipoprotein E (APOE) gene as being closely associated with cerebrovascular diseases and the recovery of neurological functions. This study aims to explore the influence of APOE gene polymorphism on cerebral oxygen saturation, cerebral electrical activity, and the clinical prognosis of patients experiencing cerebral hemorrhage. The goal is to identify potential new biomarkers that could enhance the management and treatment of individuals who have suffered from this type of bleed in the brain.To investigate this relationship, the study analyzed the ε2, ε3, and ε4 alleles of the APOE gene through gene sequencing techniques. Measurements of cerebral oxygen saturation and electrical brain activity were conducted using specialized equipment including brain oxygen monitors and electroencephalography (EEG) devices. Additionally, detailed clinical data were gathered, encompassing neurological function assessments and the duration of recovery for each patient.A comparative analysis was performed to assess the cerebral oxygen saturation levels, EEG characteristics, and overall prognosis associated with the different APOE genotypes. The findings indicated that patients carrying the APOE ε4 allele exhibited significantly impaired cerebral oxygen metabolism and diminished electrical activity in the initial stages of intracerebral hemorrhage. This impairment potentially results in a worse prognostic outlook when compared to individuals who are non-carriers of the APOE ε4 allele. Furthermore, the relationship between the pulsatility index (PR) and regional cerebral oxygen saturation (rScO2) was found to be negatively correlated. Specifically, patients with intracerebral hemorrhage who exhibited elevated PR levels alongside reduced rScO2 demonstrated poorer clinical outcomes.

Prevalence, Characteristics, and Treatment Strategy of Different Types of Heart Failure in Patients With Nonvalvular Atrial Fibrillation.

BACKGROUND: Atrial fibrillation (AF) is the most common arrhythmia in patients with heart failure (HF). Epidemiological data regarding HF in patients with AF are lacking. We describe the epidemiology, clinical features, treatment strategies, and in-hospital outcomes in patients with AF and HF. METHODS AND RESULTS: Patients with HF and nonvalvular AF in the Improving Care for Cardiovascular Disease in China-AF cohort from February 2015 to December 2019 were included. Patients were stratified by left ventricular ejection fraction into HF with reduced EF, HF with mildly reduced EF, and HF with preserved EF groups. The primary outcome was the occurrence of hospitalization for major adverse cardiovascular events, including death, cardiogenic shock, cardiac arrest, and stroke. Overall, 16 562 patients with AF and HF were included (mean age: 72.35±11.07 years; 46.1% female). HF with preserved EF (63.1%) accounted for the largest proportion, followed by HF with mildly reduced EF (19.0%) and HF with reduced EF (17.9%). Different HF subtypes in patients with AF had unique baseline demographic and clinical characteristics after multinomial logistic regression analysis. Compared with the HF with preserved EF group, hospitalization for major adverse cardiovascular events was increased in the HF with mildly reduced EF group (odds ratio=1.55 [95% CI, 1.18-2.03]) and HF with reduced EF group (odds ratio 1.60 [95% CI, 1.21-2.13]) after adjusting for confounders. CONCLUSIONS: In this large Chinese AF registry, the distribution of HF differed from the non-AF population. Patients with AF with different types of HF have unique demographic and clinical characteristics. Occurrence rates of in-hospital outcomes were higher in patients with HF with mildly reduced EF and patients with HF with reduced EF compared with the HF with preserved EF group. REGISTRATION: URL: http://www.clinicaltrials.gov; Unique identifier: NCT02309398.

Vital Characteristics Cellular Neural Network (VCeNN) for Melanoma Lesion Segmentation: A Biologically Inspired Deep Learning Approach.

Cutaneous melanoma is a highly lethal form of cancer. Developing a medical image segmentation model capable of accurately delineating melanoma lesions with high robustness and generalization presents a formidable challenge. This study draws inspiration from cellular functional characteristics and natural selection, proposing a novel medical segmentation model named the vital characteristics cellular neural network. This model incorporates vital characteristics observed in multicellular organisms, including memory, adaptation, apoptosis, and division. Memory module enables the network to rapidly adapt to input data during the early stages of training, accelerating model convergence. Adaptation module allows neurons to select the appropriate activation function based on varying environmental conditions. Apoptosis module reduces the risk of overfitting by pruning neurons with low activation values. Division module enhances the network's learning capacity by duplicating neurons with high activation values. Experimental evaluations demonstrate the efficacy of this model in enhancing the performance of neural networks for medical image segmentation. The proposed method achieves outstanding results across numerous publicly available datasets, indicating its potential to contribute significantly to the field of medical image analysis and facilitating accurate and efficient segmentation of medical imagery. The proposed method achieves outstanding results across numerous publicly available datasets, with an F1 score of 0.901, Intersection over Union of 0.841, and Dice coefficient of 0.913, indicating its potential to contribute significantly to the field of medical image analysis and facilitating accurate and efficient segmentation of medical imagery.

Application of a water-energy-carbon coupling index to evaluate the long-term operational stability of the anaerobic-anoxic-oxic-membrane bioreactor (A2/O-MBR) process under the influence of rainstorms.

In the context of global climate change, sudden rainstorms and typhoons induce fluctuations in hydraulic shocks to wastewater treatment plants (WWTPs) in coastal areas, causing two challenges of stable effluent quality and low-carbon operation. We established a quantitative evaluation method for resistance of wastewater treatment processes to hydraulic shocks based on the water-energy-carbon nexus using operational data from a WWTP in southeast coastal China from July 2018 to December 2022. The effects of hydraulic shocks on the operational stability of the anaerobic-anoxic-oxic-membrane bioreactor (A2/O-MBR) process were analyzed following five steps. The results showed that the gray water footprint (GWF) of the process was 9.3% lower than that of the A2/O process. The energy footprint (ENF) and carbon footprint (CF) were approximately 2.1 times and 1.7 times higher than those of the A2/O process, respectively. The resistance to hydraulic shocks of the A2/O-MBR process is approximately 5.5 times higher than that of the A2/O process. In conclusion, the A2/O-MBR process exhibits higher process operational stability when subjected to hydraulic shocks, which is more conducive to the efficient and stable operation of WWTPs in rainstorm and typhoon-prone areas. The evaluation methodology provides qualitative technical support for selecting upgrading processes for WWTPs in different regions.

SC-Unext: A Lightweight Image Segmentation Model with Cellular Mechanism for Breast Ultrasound Tumor Diagnosis.

Automatic breast ultrasound image segmentation plays an important role in medical image processing. However, current methods for breast ultrasound segmentation suffer from high computational complexity and large model parameters, particularly when dealing with complex images. In this paper, we take the Unext network as a basis and utilize its encoder-decoder features. And taking inspiration from the mechanisms of cellular apoptosis and division, we design apoptosis and division algorithms to improve model performance. We propose a novel segmentation model which integrates the division and apoptosis algorithms and introduces spatial and channel convolution blocks into the model. Our proposed model not only improves the segmentation performance of breast ultrasound tumors, but also reduces the model parameters and computational resource consumption time. The model was evaluated on the breast ultrasound image dataset and our collected dataset. The experiments show that the SC-Unext model achieved Dice scores of 75.29% and accuracy of 97.09% on the BUSI dataset, and on the collected dataset, it reached Dice scores of 90.62% and accuracy of 98.37%. Meanwhile, we conducted a comparison of the model's inference speed on CPUs to verify its efficiency in resource-constrained environments. The results indicated that the SC-Unext model achieved an inference speed of 92.72 ms per instance on devices equipped only with CPUs. The model's number of parameters and computational resource consumption are 1.46M and 2.13 GFlops, respectively, which are lower compared to other network models. Due to its lightweight nature, the model holds significant value for various practical applications in the medical field.

In-hospital therapies and determinants of treatment strategy selection in patients with atrial fibrillation and left ventricular systolic dysfunction in China: a retrospective study based on the Improving Care for Cardiovascular Disease in China-Atrial Fibrillation (CCC-AF) project, 2015-2019.

OBJECTIVES: The optimal treatment strategy remains debatable in patients with atrial fibrillation (AF) and heart failure. Our objectives were to summarise in-hospital therapies and determine factors associated with treatment strategy selections. DESIGN: A retrospective study analysing the Improving Care for Cardiovascular Disease in China-Atrial Fibrillation (CCC-AF) project from 2015 to 2019. SETTING: The CCC-AF project included patients from 151 tertiary and 85 secondary hospitals across 30 provinces in China. PARTICIPANTS: Patients with AF and left ventricular systolic dysfunction (LVSD, defined as left ventricular ejection fraction<50%) were included, with 5560 patients in the study sample. METHODS: Patients were classified by treatment strategies. In-hospital treatments and trends of therapies were analysed. Multiple logistic regression models were used to find determinants of treatment strategies. RESULTS: Rhythm control therapies were used in 16.9% of patients with no significant trends (p trend=0.175). Catheter ablation was used in 5.5% of patients, increasing from 3.3% in 2015 to 6.6% in 2019 (p trend<0.001). Factors negatively associated with rhythm control included increased age (OR 0.973, 95% CI 0.967 to 0.980), valvular AF (OR 0.618, 95% CI 0.419 to 0.911), AF types (persistent: OR 0.546, 95% CI 0.462 to 0.645; long-standing persistent: OR 0.298, 95% CI 0.240 to 0.368), larger left atrial diameters (OR 0.966, 95% CI 0.957 to 0.976) and higher Charlson Comorbidity Index scores (CCI 1-2: OR 0.630, 95% CI 0.529 to 0.750; CCI≥3: OR 0.551, 95% CI 0.390 to 0.778). Higher platelet counts (OR 1.025, 95% CI 1.013 to 1.037) and prior rhythm control attempts (electrical cardioversion: OR 4.483, 95% CI 2.369 to 8.483; catheter ablation: OR 4.957, 95% CI 3.072 to 7.997) were positively associated with rhythm control strategies. CONCLUSION: In China, non-rhythm control strategy remained the dominant choice in patients with AF and LVSD. Age, AF types, prior treatments, left atrial diameters, platelet counts and comorbidities were major determinants of treatment strategies. Guideline-adherent therapies should be further promoted. STUDY REGISTRATION NUMBER: NCT02309398.

Effects of apolipoprotein E polymorphism on cerebral oxygen saturation, cerebral perfusion, and early prognosis after traumatic brain injury.

OBJECTIVE: To investigate the effects of the apolipoprotein E (APOE) gene on oxygen saturation and cerebral perfusion in the early stages of traumatic brain injury (TBI). METHODS: This study included 136 consecutive TBI patients and 51 healthy individuals. The APOE genotypes of all subjects were determined using quantitative fluorescence polymerase chain reaction (QF-PCR). Regional cerebral oxygen saturation (rScO2) of patients with TBI and normal subjects was monitored using near-infrared spectroscopy (NIRS). Computed tomography (CT) perfusion was used to obtain cerebral perfusion in patients with TBI and normal subjects. RESULTS: In the TBI group, the rScO2 of APOEε4 carriers (53.06 ± 6.87%) was significantly lower than that of non-carriers (58.19 ± 5.83%, p < 0.05). Meanwhile, the MTT of APOEε4 carriers (6.75 ± 1.30 s) was significantly longer than that of non-carriers (5.87 ± 1.00 s, p < 0.05). Furthermore, correlation analysis showed a negative correlation between rSCO2 and MTT in patients with TBI. Both the univariate and multifactorial logistic regression analyses revealed that APOE ε4, hypoxia, MTT >5.75 s, Marshall CT Class, and GCS were independent risk factors for early poor prognosis in patients with TBI. CONCLUSION: Both cerebral perfusion and cerebral oxygen were significantly impaired after TBI, and low cerebral perfusion and hypoxia were related to poor prognosis of patients with TBI. Compared with APOE ε4 non-carriers, APOE ε4 carriers not only had poorer cerebral perfusion and cerebral oxygen metabolism but also worse prognosis in the early stages of TBI. Furthermore, a negative correlation was observed between the rSCO2 and MTT levels. In addition, both CT perfusion scanning (CTP) and NIRS are reliable for monitoring the condition of patients with TBI in the neurological intensive care unit (NICU).

Influence on Elastic Wave Propagation Behavior in Polymers Composites: An Analysis of Inflection Phenomena.

Particulate polymer composites (PPCs) are widely applied under different elastic wave loading conditions in the automobile, aviation, and armor protection industries. This study investigates the elastic wave propagation behavior of a typical PPC, specifically a Cu/poly (methyl methacrylate) (PMMA) composite, with a wide range of particle contents (30-65 vol. %) and particle sizes (1-100 µm). The results demonstrate an inflection phenomenon in both the elastic wave velocity and attenuation coefficient with increasing volume content. In addition, the inflection point moves to the direction of low content with the increase in particle size. Notably, the elastic wave velocity, attenuation, and wavefront width significantly increased with the particle size. The inflection phenomenon of elastic wave propagation behavior in PPCs is demonstrated to have resulted from particle interaction using the classical scattering theory and finite element analysis. The particle interaction initially intensified and then reduced with increasing particle content. This study elucidates the underlying mechanism governing the elastic wave propagation behavior of high particle content PPCs and provides guidelines for the design and application of wave-absorbing composites.

A High Gain Embedded Helix and Dielectric Rod Antenna with Low Side Lobe Levels for IoT Applications.

In this paper, a novel embedded helix dielectric rod antenna is presented for high gain radiation with circular polarization (CP) and low side lobe levels for IoT Applications. Different from the conventional dielectric rod antennas, this proposed antenna is an integrated structure that combines the advantages of the helix and dielectric rod antennas. The presented antenna mainly consists of three parts: a tapered helix as primary feeding for CP, a dielectric rod with printed loops embedded for higher directivity, and a dielectric rod end for improving the gain further. After studying and analyzing the working principles of each part, an optimum design operating at 8-9.7 GHz is carried out as an example. A prototype is also fabricated and tested. The measured results show that the prototype can provide 18.41 dB maximum gain within the length of 7.7 λ. The side lobe level is below -20 dB, and the axial ratio is better than 1.14 dB in the whole frequency band. Compared with the traditional helix antenna and dielectric rod antenna with the same electric length, the presented antenna has a higher gain with a lower side lobe level and with good polarization purity.

Prediction of early prognosis after traumatic brain injury by multifactor model.

AIMS: To design a model to predict the early prognosis of patients with traumatic brain injury (TBI) based on parameters that can be quickly obtained in emergency conditions from medical history, physical examination, and supplementary examinations. METHODS: The medical records of TBI patients who were hospitalized in two medical institutions between June 2015 and June 2021 were collected and analyzed. Patients were divided into the training set, validation set, and testing set. The possible predictive indicators were screened after analyzing the data of patients in the training set. Then prediction models were found based on the possible predictive indicators in the training set. Data of patients in the validation set and the testing set was provided to validate the predictive values of the models. RESULTS: Age, Glasgow coma scale score, Apolipoprotein E genotype, damage area, serum C-reactive protein, and interleukin-8 (IL-8) levels, and Marshall computed tomography score were found associated with early prognosis of TBI patients. The accuracy of the early prognosis prediction model (EPPM) was 80%, and the sensitivity and specificity of the EPPM were 78.8% and 80.8% in the training set. The accuracy of the EPPM was 79%, and the sensitivity and specificity of the EPPM were 66.7% and 86.2% in the validation set. The accuracy of the early EPPM was 69.1%, and the sensitivity and specificity of the EPPM were 67.9% and 77.8% in the testing set. CONCLUSION: Prediction models integrating general information, clinical manifestations, and auxiliary examination results may provide a reliable and rapid method to evaluate and predict the early prognosis of TBI patients.

Development and Validation of an Automatic System for Intracerebral Hemorrhage Medical Text Recognition and Treatment Plan Output.

The main purpose of the study was to explore a reliable way to automatically handle emergency cases, such as intracerebral hemorrhage (ICH). Therefore, an artificial intelligence (AI) system, named, H-system, was designed to automatically recognize medical text data of ICH patients and output the treatment plan. Furthermore, the efficiency and reliability of the H-system were tested and analyzed. The H-system, which is mainly based on a pretrained language model Bidirectional Encoder Representations from Transformers (BERT) and an expert module for logical judgment of extracted entities, was designed and founded by the neurosurgeon and AI experts together. All emergency medical text data were from the neurosurgery emergency electronic medical record database (N-eEMRD) of the First Affiliated Hospital of Chongqing Medical University, Chongqing Emergency Medical Center, and Chongqing First People's Hospital, and the treatment plans of these ICH cases were divided into two types. A total of 1,000 simulated ICH cases were randomly selected as training and validation sets. After training and validating on simulated cases, real cases from three medical centers were provided to test the efficiency of the H-system. Doctors with 1 and 5 years of working experience in neurosurgery (Doctor-1Y and Doctor-5Y) were included to compare with H-system. Furthermore, the data of the H-system, for instance, sensitivity, specificity, accuracy, positive predictive value (PPV), negative predictive value (NPV), and the area under the receiver operating characteristics curve (AUC), were calculated and compared with Doctor-1Y and Doctor-5Y. In the testing set, the time H-system spent on ICH cases was significantly shorter than that of doctors with Doctor-1Y and Doctor-5Y. In the testing set, the accuracy of the H-system's treatment plan was 88.55 (88.16-88.94)%, the specificity was 85.71 (84.99-86.43)%, and the sensitivity was 91.83 (91.01-92.65)%. The AUC value of the H-system in the testing set was 0.887 (0.884-0.891). Furthermore, the time H-system spent on ICH cases was significantly shorter than that of doctors with Doctor-1Y and Doctor-5Y. The accuracy and AUC of the H-system were significantly higher than that of Doctor-1Y. In addition, the accuracy of the H-system was more closed to that of Doctor-5Y. The H-system designed in the study can automatically recognize and analyze medical text data of patients with ICH and rapidly output accurate treatment plans with high efficiency. It may provide a reliable and novel way to automatically and rapidly handle emergency cases, such as ICH.

APOE gene polymorphism alters cerebral oxygen saturation and quantitative EEG in early-stage traumatic brain injury.

OBJECTIVE: To investigate the influence of apolipoprotein E (APOE) gene polymorphism on regional cerebral oxygen saturation (rScO2) and quantitative electroencephalogram (QEEG) at the early phase of adult traumatic brain injury (TBI). METHODS: clinical data of TBI patients who were admitted to the neurosurgery intensive care unit (NICU) were retrospectively evaluated and studied, and data of healthy volunteers were recruited as control. The APOE genotypes were genotyped by quantitative fluorescent polymerase chain reaction (QF-PCR). The rScO2 and brainelectricalactivityof all the participants involved in this research were measured by near-infrared spectroscopy (NIRS) and QEEG respectively. RESULTS: The average rScO2 of TBI patients was significantly lower than that of the normal controls (P < 0.0001). And the EEG of the TBI patients has showed more irregular slow-wave activities than that of the normal controls. Furthermore, the above changes were more significant in the APOE ε4 carriers in the early stage of TBI patients. CONCLUSIONS: The APOE ε4 allele may be associated with poor rScO2 and more slow-wave activities at the early stage of TBI. SIGNIFICANCE: To clarify the effect of APOE gene polymorphism on the condition of patients with TBI may be helpful for the design and management of individualized treatment programs.

Artery and venous sinus occlusion image score (AVOIS): A novel method to evaluate occlusive cerebral arteries and venous diseases.

AIM: To establish an artery and venous sinus occlusion image score (AVOIS) which is compatible in both cerebral arteries and venous system diseases. METHODS: A total of 188 consecutive patients with the final diagnosis of anterior circulation infarct (ACI) and 56 consecutive patients with cerebral venous and sinus thrombosis (CVST) were retrospectively studied. The AVOIS was developed based on the severity of occlusive changes of main intracranial arteries and venous sinuses (present = 0, partial occlusion = 1, absent = 2), and divided into four groups (CVST group: 0, 1-5, 6-10, >10. ACI group: 0, 1-5, 6-10, >10) arbitrarily. A receiver operating characteristic (ROC) curve was applied to discover the sensitivity and specificity of AVOIS. The National Institutes of Health Stroke Scale (NIHSS), Clot Burden Score (CBS) were set as the reference. Logistic regression models were developed to adjust for baseline clinical variables and AVOIS. Length of hospital stay (LOS) was also evaluated using the Kaplan-Meier estimator. RESULTS: For the CVST group, a positive correlation between AVOIS and NIHSS was discovered (Spearman's ρ = 0.54, p < 0.001). For the ACI group, ROC showed relatively high sensitivity (84.8%) and specificity (81.8%). Besides, the probability of time to discharge was significantly different among the AVOIS subgroups as well (p < 0.001). CONCLUSION: The AVOIS can be used to evaluate the treatment of patients with acute stroke caused by cerebral venous sinus thrombosis and anterior circulation large vessel occlusion. It is a reliable and convenient method that may help prompt prognosis and guide the treatment of individual patients.

The Potential Migrated Mechanism of Water-Soluble Components in Pellets Prepared by Wet Extrusion/Spheronization: Effect of Drying Rate.

INTRODUCTION: At present, there are numerous researches on the migration of components in tablets and granules, however, the investigation in the pharmaceutical literatures concerning the effect of drying rate on the migration of water-soluble components of pellets is limited. Temperature and Relative Humidity (RH) are crucial parameters during the drying process, which is an essential step in the preparation of pellets via wet extrusion/spheronization. To quantify these variables, the water loss percentage of pellets per minute is defined as the drying rate. AIM: The study aimed to investigate the influence of drying rate on the migration of water-soluble components in wet pellets and the potential migrated mechanism. METHODS: The pellets containing tartrazine as a water-soluble model drug and microcrystalline cellulose as a matrix former were prepared by extrusion/spheronization and dried at four different drying temperatures and relative humidity. Afterwards, the extent of migrated tartrazine was assessed regarding appearance, in-vitro dissolution test, Differential Scanning Calorimetry, X-Ray Powder Diffraction, Attenuated total reflectance Fourier transform infrared spectroscopy and Confocal Raman Mapping. RESULTS: Results demonstrated that red spots of tartrazine appeared on the surface of pellets and more than 40% tartrazine were burst released within 5 minutes when pellets were dried at 60°C/RH 10%. When pellets were dried at 40°C/RH 80%, none of these aforementioned phenomena were observed. CONCLUSION: In conclusion, the faster the drying rate was, the more tartrazine migrated to the exterior of pellets. Adjusting drying temperature and relative humidity appropriately could inhibit the migration of water-soluble components within wet extrusion/spheronization pellets.

Brachial-Ankle Pulse Wave Velocity Predicts New-Onset Hypertension and the Modifying Effect of Blood Pressure in a Chinese Community-Based Population.

Brachial-ankle pulse wave velocity (baPWV) was proven to be a prognostic indicator of cardiovascular events. However, the modifying effect of blood pressure (BP) on the longitudinal association between baPWV and new-onset hypertension is not well established. This study included 1849 non-hypertensive Chinese subjects from Shougang cohort study during December 2011 to July 2014. BaPWV was obtained using an Omron Colin BP-203RPE III device. Multivariate logistic regression models were used to evaluate associations of baPWV and outcomes. During a mean follow-up time of 2.36 years, 248 (13.41%) developed hypertension. BaPWV independently and gradably predicted the risk of incident hypertension and the SBP level at revisit (odds ratio or ß (95% confidence interval) for participants with baPWV in quartile 4 vs. quartile 1: 2.72 (1.54, 4.78) for incident hypertension and 5.92 (4.26, 7.58) for SBP, P for trend: <0.001) after adjusting demonstrated risk factors. Besides, the effects of baseline baPWV on either incident hypertension or SBP at revisit were interactively modified by the level of baseline SBP; the effect size increased as the SBP level decreased. baPWV independently predicted the risk of hypertension and BP progression, modified by the level of SBP at baseline in this Chinese community-based population. The combination of baPWV and SBP can help differentiate the potential high-risk candidates who will develop hypertension quickly and benefit from early diagnosis and treatment.

Tolerogenic properties of CD206+ macrophages appeared in the sublingual mucosa after repeated antigen-painting.

The sublingual mucosa (SLM) in the oral cavity is utilized as the site for sublingual immunotherapy to induce tolerance against allergens. We previously reported that CD206+ round-type macrophage-like cells were induced in the SLM after repeated antigen (e.g. cedar pollen or fluorescein isothiocyanate (FITC))-painting. In this study, we examined the phenotypic and functional properties of CD206+ cells induced by repeated FITC-painting on the SLM. CD206+ cells after the repeated FITC-painting possessed a macrophage-like CD11b+Ly6C+ F4/80+CD64+ phenotype and expressed TIM-4, which was expressed in tolerogenic tissue-resident macrophages, at a high level. SLM CD206+ cells preferentially expressed molecules related to endocytosis and homeostatic processes, including the novel B7 family of immune checkpoint molecules, as assessed by microarray analyses. SLM CD206+ cells showed preferential expression of M2-related genes such as Fizz1, Aldh1a1 and Aldh1a2 but not Ym-1 and Arginase-1. A CD206+ cell-rich status inhibited OVA-specific CD4+ T-cell responses but reciprocally enhanced the proportion of both IL-10+CD4+ cells and Foxp3+ regulatory T-cells in regional lymph nodes. Co-culture of CD206+ cells with dendritic cells (DCs) showed that IL-12 production was suppressed in DCs concurrent with the decline of the MHC class IIhiCD86+ population, which was restored by neutralization of IL-10. These results demonstrate SLM CD206+ cells show the feature of tolerogenic macrophages and down-regulate the antigen-presenting cell function of mature DCs resulting in the inhibition of CD4+ T-cell responses.

Dysregulated serum lipid profile and its correlation to disease activity in young female adults diagnosed with systemic lupus erythematosus: a cross-sectional study.

BACKGROUND: Recent studies showed that dyslipidemia could be a critical factor in the progression of cardiovascular disease in systemic lupus erythematosus (SLE). The aim of the present study was to describe the relationship between serum lipid profile and SLE disease activity in young female adults with SLE. METHODS: Seventy-one female subjects diagnosed with SLE aged 20~30 years were enrolled. Serum lipid profile including TC, TG, HDL-C, LDL-C, VLDL-C, Apo A, Apo B, and Apo E were evaluated between control and young female SLE patients. Univariate correlation analyses were performed to explore the correlation between serum lipid levels and SLE disease activity. RESULTS: Our results showed that TG and VLDL-C levels were significantly increased in young female SLE as compared to control, with TC, HDL-C, LDL-C, Apo A, and Apo B significantly reduced. Meanwhile, univariate correlation analyses showed negative correlations between SLE disease activity index and HDL-C, LDL-C, Apo A, and Apo B; with positive correlations between SLE disease activity index and TG and VLDL-C. CONCLUSION: Serum lipid profile was significantly dysregulated in young female SLE patients. Moreover, SLE disease activity was correlated to the serum lipid levels, supporting the notion that the young patients with SLE might also have a higher risk of cardiovascular disease.

Evaluating supersaturation in vitro and predicting its performance in vivo with Biphasic gastrointestinal Simulator: A case study of a BCS IIB drug.

This study aimed to develop an evaluation approach for supersaturation by employing an in vitro bio-mimicking apparatus designed to predict in vivo performance. The Biphasic Gastrointestinal Simulator (BGIS) is composed of three chambers with absorption phases that represent the stomach, duodenum, and jejunum, respectively. The concentration of apatinib in each chamber was detected by fiber optical probes in situ. The dissolution data and the pharmacokinetic data were correlated by GastroplusTM. The precipitates were characterized by polarizing microscope, Scanning Electron Microscopy, Powder X-ray diffraction and Differential scanning calorimetry. According to the results, Vinylpyrrolidone-vinyl acetate copolymer (CoPVP) prolonged supersaturation by improving solubility and inhibiting crystallization, while Hydroxypropyl methylcellulose (HPMC) prolonged supersaturation by inhibiting crystallization alone. Furthermore, a predictive in vitro-in vivo correlation was established, which confirmed the anti-precipitation effect of CoPVP and HPMC on in vitro performance and in vivo behavior. In conclusion, CoPVP and HPMC increased and prolonged the supersaturation of apatinib, and then improved its bioavailability. Moreover, BGIS was demonstrated to be a significant approach for simulating in vivo conditions for in vitro-in vivo correlation in a supersaturation study. This study presents a promising approach for evaluating supersaturation, screening precipitation inhibitors in vitro, and predicting their performances in vivo.