Structure Property Relationship of Micellar Waterborne Poly(Urethane-Urea): Tunable Mechanical Properties and Controlled Release Profiles with Amphiphilic Triblock Copolymers.

Waterborne polyurethane (WPU) has attracted significant interest as a promising alternative to solvent-based polyurethane (SPU) due to its positive impact on safety and sustainability. However, significant limitations of WPU, such as its weaker mechanical strength, limit its ability to replace SPU. Triblock amphiphilic diols are promising materials to enhance the performance of WPU due to their well-defined hydrophobic-hydrophilic structures. Yet, our understanding of the relationship between the hydrophobic-hydrophilic arrangements of triblock amphiphilic diols and the physical properties of WPU remains limited. In this study, we show that by controlling the micellar structure of WPU in aqueous solution via the introduction of triblock amphiphilic diols, the postcuring efficiency and the resulting mechanical strength of WPU can be significantly enhanced. Small-angle neutron scattering confirmed the microstructure and spatial distribution of hydrophilic and hydrophobic segments in the engineered WPU micelles. In addition, we show that the control of the WPU micellar structure through triblock amphiphilic diols renders WPU attractive in the applications of controlled release, such as drug delivery. Here, curcumin was used as a model hydrophobic drug, and the drug release behavior from WPU-micellar-based drug delivery systems was characterized. It was found that curcumin-loaded WPU drug delivery systems were highly biocompatible and exhibited antibacterial properties in vitro. Furthermore, the sustained release profile of the drug was found to be dependent on the structure of the triblock amphiphilic diols, suggesting the possibility of controlling the drug release profile via the selection of triblock amphiphilic diols. This work shows that by shedding light on the structure-property relationship of triblock amphiphilic diol-containing WPU micelles, we may enhance the applicability of WPU systems and move closer to realizing their promising potential in real-life applications.

Yang-Yin-Jie-Du decoction overcomes gefitinib resistance in non-small cell lung cancer via down-regulation of the PI3K/Akt signalling pathway.

CONTEXT: Yang-Yin-Jie-Du Decoction (YYJDD) was used to improve gefitinib efficacy in our clinical practice, but its mechanism remains unclear. OBJECTIVE: This study explored if YYJDD could reverse gefitinib resistance. MATERIALS AND METHODS: H1975 cells were exposed to control, 10 µM gefitinib, 3.2 mg/mL YYJDD or combination treatment. Cell viability was detected by MTT during 0-96 h. Apoptosis and the PI3K/Akt proteins were tested by flow cytometry and western-blot at 24 h. LY294002 was applied to further determine the role of the PI3K/Akt. 23 BALB/c nude xenograft mice received normal saline (n = 5), 80 mg/kg gefitinib (n = 6), 2.35 g/kg lyophilised powder of YYJDD (n = 6) or combination treatment (n = 6) by gavage for 4 weeks and submitted to TUNEL, immunohistochemistry, and western-blot. RESULTS: In vitro, gefitinib (IC50: 20.68 ± 2.06 µM) and YYJDD (IC50: 6.6 ± 0.21 mg/mL) acted in a moderate synergistic way. Combination treatment inhibited cell viability from 100% to 25.66%. Compared to gefitinb (33.23 ± 3.99%), cell apoptosis was increased with combination treatment (54.11 ± 7.32%), accompanied by down-regulation of the PI3K/Akt. LY294002 further inhibited cell viability, increased apoptosis, and down-regulated p-Akt/Akt. In vivo, the tumour sizes in the combination group (1165.13 ± 157.79 mm3) were smaller than gefitinib alone (1630.66 ± 208.30 mm3). The positive rate of TUNEL staining was increased by combination treatment (22.33 ± 2.75%) versus gefitinib (7.37 ± 0.87%), while the PI3K/Akt was down-regulated. DISCUSSION AND CONCLUSION: YYJDD has potential to overcome gefitinib resistance. Future investigations should be focussed on its specific targets.

Mapping the research of nursing in Parkinson's disease: a bibliometric and quantitative analysis.

Background: Parkinson's disease (PD) is a chronic and progressive neurodegenerative disorder. Clinically, the therapeutic strategy of PD could only alleviate the symptoms. Nursing plays a crucial role in providing patient education, symptom management, and psychosocial support. This study aims to analyze the current state and prospects of research in the field of Parkinson's disease (PD) and its associated nursing care through bibliometric methods to explore the trends that May guide its future development. Methods: Literature related to Parkinson's disease and nursing care was systematically searched by the Web of Science database from 1991 to 2023. Quantitative analysis of cooperative networks was conducted using bibliometric tools VOSviewer and CiteSpace. Results: The analysis covered 2,649 publications in the field of PD and nursing care, authored by 12,576 researchers from 3,869 institutions across 94 countries. The number of articles has steadily increased over the past 20 years. In this research field, the United States and the United Kingdom emerged as leading countries, and Radboud Universiteit Nijmegen was positioned as an international hub. Movement Disorders was identified as the journal with the highest output and with the most co-citation. Prof. Bastiaan R. Bloem published the most papers in the area, and Prof. Per Odin had the highest average citation. The major fields of these publications are clinical neurology, geriatrics & gerontology, multidisciplinary sciences, and health care sciences & services. Hot topics in the field predominantly revolve around Parkinson's disease, quality of life, and dementia. Conclusion: Research in Parkinson's disease and nursing care is experiencing a period of rapid growth, with continuous expansion in research scope and depth of investigation. One of the trends identified is the increasing focus on quality of life and the management of dementia in PD patients, reflecting the importance of these areas in research. The study further suggests that future advancements in the field May rely significantly on strengthening international collaborations and addressing global disparities in resource distribution, particularly by promoting research inclusivity and cooperation among low-resource countries.

Clinical Experience of External Application of Clearing Heat and Removing Dampness in Relieving Grade 2 to 3 Rash Caused by Programed Cell Death Protein 1 (PD-1)/Programed Cell Death Ligand 1 (PD-L1) Inhibitors: A Single-Center Retrospective Study.

OBJECTIVE: In China, grade 2 to 3 immune-related rash will probably lead to the interruption of immunotherapy. Corticosteroid (CS) is the main treatment, but not always effective. The external application of clearing heat and removing dampness, which is represented by Qing-Re-Li-Shi Formula (QRLSF), has been used in our hospital to treat immune-related cutaneous adverse events (ircAEs) for the last 5 years. The purpose of this study was to discuss its efficacy and safety in the treatment of grade 2 to 3 rash. METHODS: A retrospective study of patients with grade 2 to 3 immune-related rash in our hospital from December 2019 to December 2022 was conducted. These patients received QRLSF treatment. Clinical characteristics, treatment outcome, and health-related quality of life (HrQoL) were analyzed. RESULTS: Thirty patients with grade 2 to 3 rash (median onset time: 64.5 days) were included. The skin lesions of 24 cases (80%) returned to grade 1 with a median time of 8 days. The accompanying symptoms were also improved with median time of 3 to 4 days. The addition of antihistamine (AH) drug didn't increase the efficacy of QRLSF (AH + QRLSF: 75.00% vs QRLSF: 83.33%, P = .66). No significant difference was observed in the efficacy of QRLSF treatment regardless of whether patients had previously received CS therapy (untreated population: 88.24% vs treated population: 69.23%, P = .36). During 1-month follow-up, 2 cases (8.33%) underwent relapses. In terms of HrQoL, QRLSF treatment could significantly reduce the median scores of all domains of Skindex-16, including symptoms (39.58 vs 8.33, P < .0001), emotions (58.33 vs 15.48, P < .0001), functioning (46.67 vs 13.33, P < .0001) and composite (52.60 vs 14.06, P < .0001). CONCLUSION: External application of clearing heat and removing dampness was proven to be an effective and safe treatment for such patients. In the future, high-quality trials are required to determine its clinical application in the field of ircAEs.

Prevalence and molecular characteristics of intestinal pathogenic Escherichia coli isolated from diarrheal pigs in Southern China.

Intestinal pathogenic Escherichia coli (InPEC) is one of the most common causes of bacterial diarrhea in farm animals, including profuse neonatal diarrhea and post weaning diarrhea (PWD) in piglets. In this study, we investigated the prevalence of InPEC and associated primary virulence factors among 543 non-duplicate E. coli isolates from diarrheal pigs from 15 swine farms in southern China. Six major virulence genes associated with InPEC were identified among 69 (12.71 %) E. coli isolates and included est (6.62 %), K88 (4.79 %), elt (3.68 %), eae (1.47 %), stx2 (0.92 %) and F18 (0.55 %). Three pathotypes of InPEC were identified including ETEC (8.10 %), EPEC (1.29 %) and STEC/ETEC (0.92 %). In particular, K88 was only found in ETEC from breeding farms, whereas F18 was only present in STEC/ETEC hybrid from finishing farms. Whole genome sequence analysis of 37 E. coli isolates revealed that InPEC strains frequently co-carried multiple antibiotic resistance gene (ARG). est, elt and F18 were also found to co-locate with ARGs on a single IncFIB/IncFII plasmid. InPEC isolates from different pathotypes also possessed different profiles of virulence genes and antimicrobial resistance genes. Population structure analysis demonstrated that InPEC isolates from different pathotypes were highly heterogeneous whereas those of the same pathotype were extremely similar. Plasmid analysis revealed that K88 and/or est/elt were found on pGX18-2-like/pGX203-2-like and pGX203-1-like IncFII plasmids, while F18 and elt/est, as well as diverse ARGs were found to co-locate on IncFII/IncFIB plasmids with a non-typical backbone. Moreover, these key virulence genes were flanked by or adjacent to IS elements. Our findings indicated that both clonal expansion and horizontal spread of epidemic IncFII plasmids contributed to the prevalence of InPEC and the specific virulence genes (F4, F18, elt and est) in the tested swine farms.

Oenothein B ameliorates hepatic injury in alcoholic liver disease mice by improving oxidative stress and inflammation and modulating the gut microbiota.

Introduction: Alcoholic liver disease (ALD) is a global health problem for which there is no current food and drug administration (FDA)-approved therapy. Oenothein B (OEB) is a macrocyclic dimer ellagic tannin that possesses abundant biological activities including antioxidant, anti-inflammation, antitumor, immunomodulatory, and antimicrobial properties. Materials and methods: In this study, the hepatoprotective effect of OEB against ALD was investigated in vivo and in vitro. Results: We found that OEB treatment dramatically reduced alcohol-induced hepatic injury, as evidenced by decreased levels of aminotransferases and inflammatory biomarkers and increased antioxidant capacity in OEB-treated groups. Discussion: OEB treatment alleviated oxidative stress by upregulating the Keap1/Nrf2 signaling pathway and inhibited inflammation by downregulating the TLR4/NF-κB signaling pathway. Additionally, OEB treatment positively improved alcohol-induced intestinal microbial dysbiosis by modulating the structure and composition of gut microbiota. Interestingly, we observed the increasement of short-chain fatty acid (SCFA) producers (Muribaculaceae) and the decreasement of Gram-negative bacteria (Akkermansia) in the OEB treatment groups, which may contribute to the inhibition of hepatic oxidative stress and inflammation via the gut-liver axis. In summary, our findings indicate that OEB is a promising therapeutic strategy for preventing and treating ALD.

Prevalence and associated factors of sexual dysfunction in cervical cancer patients.

INTRODUCTION: Cervical cancer (CC), compared with other gynecological cancers, has critical implications for women's sexual lives. For most Asian people, the issue of sexual dysfunction (SD) is treated as a taboo especially in a conservative culture. As a result, little is known about the prevalence of SD among CC patients. AIMS: The purpose of this study was to investigate the prevalence of SD and associated factors among CC patients. METHODS: We used a cross-sectional correlation design with the purposive sampling to recruit 105 CC patients from a hospital in Northern Taiwan. A structured questionnaire was used in this study to collect demographic data, disease characteristics, and information provided by the Chinese version of the Female Sexual Function Index scale. Data were analyzed by descriptive statistics, independent t-test, chi-square test, and multiple logistic regression. MAIN OUTCOME MEASURE: The prevalence of SD and the main predictors for SD were determined. RESULTS: The crude prevalence and age-standardized prevalence of SD were 66.67% and 55%, respectively. CC patients with a lower level of education (≤9th grade) (adjusted odds ratio [AOR]: 3.14; 95% confidence interval [CI]: 1.51-10.37), who were older (AOR: 1.16; 95% CI: 1.07-1.25), who had received no sexual-counseling services prior to therapy or later (AOR: 4.98; 95% CI: 2.31-9.71), or were stage II or above (AOR: 4.34; 95% CI: 1.65-19.09) showed a significantly higher risk of SD compared with those without these conditions. CONCLUSIONS: Our findings are beneficial to health-care providers by identifying the prevalence of SD and by pinpointing those groups with a higher predisposition of having SD, which will allow the provision of appropriate rehabilitation.

Neoadjuvant therapy of cetuximab combined with chemoradiotherapy in rectal cancer: A single-arm meta-analysis of noncomparative clinical studies and randomized controlled trials.

OBJECTIVE: Preoperative chemoradiotherapy combined with radical resection has reduced local recurrence rates in rectal cancer. Cetuximab shows improvement in rectal cancer treatment. But the role for neoadjuvant therapy of cetuximab combined with chenmoradiotherapy in rectal cancer remains unclear. The present study aimed to use meta-analytical techniques to assess its benefit and risk. MATERIALS AND METHODS: We searched PubMed, the Cochrane Library, Embase to identify the correlational non-comparative clinical studies and randomized controlled trials (RCTs). The primary endpoints of interest were pathological complete response (pCR), complete response (CR), partial response (PR), stable disease, progressive disease (PD), R0-resection, R1-resection, and R2-resection. The secondary included any grade of toxicity. RESULTS: Eleven investigations (9 noncomparative open-label cohort studies and 2 randomized controlled trials) involving 550 patients were ultimately included. The pooled estimates of pCR was 10% (95% confidence interval [CI]: 7%-13%, I2 = 55.9%). Simultaneously, only a small amount of patients achieved CR (11%, 95% CI: 7%-15%, I2 = 44.0%), which was consistent with pCR. Besides, R0 resection (93%, 95% CI: 90%-96%, I2 = 16.5%) seemed to be increased but need further exploration. The safety was also calculated, and most of the toxicities were moderate. CONCLUSION: Neoadjuvant therapy of cetuximab combined with chemoradiotherapy could not improve pCR. The raise of R0-resection rate needed to be verified by more high-quality and well-designed RCTs. Meanwhile, the morbidity of toxicity was relatively mild and acceptable.

Stevens-Johnson syndrome/toxic epidermal necrolysis successfully treated with Chinese herbal medicine Pi-Yan-Ning: A case report.

Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) is a rare adverse cutaneous reaction with a low incidence and high mortality. Despite posing a serious threat to patients' health and lives, there is no high-quality evidence for a standard treatment regimen. Here we report the case of a 62-year-old man with stage IV pancreatic cancer who experienced immunotherapy-induced SJS/TEN. After consensus-based regular treatments at a local hospital, his symptoms became worse. Thus, he consented to receive Chinese herbal medicine (CHM) therapy. The affected parts of the patient were treated with the CHM Pi-Yan-Ning which was applied externally for 20 min twice a day. After 7 days of treatment, the dead skin began peeling away from the former lesions that had covered his hands, feet, and lips, indicating that skin had regenerated. After 12 days of treatment, the patient's skin was completely recovered. In this case, SJS/TEN was successfully treated with Pi-Yan-Ning, suggesting that there might be tremendous potential for the use of Pi-Yan-Ning in the treatment of severe skin reactions to drug treatments. Further basic investigations and clinical trials to explore the mechanism and efficacy are needed.

Direct interaction of focal adhesion kinase (FAK) with Met is required for FAK to promote hepatocyte growth factor-induced cell invasion.

Focal adhesion kinase (FAK) has been implicated to be a point of convergence of integrin and growth factor signaling pathways. Here we report that FAK directly interacts with the hepatocyte growth factor receptor c-Met. Phosphorylation of c-Met at Tyr-1349 and, to a lesser extent, Tyr-1356 is required for its interaction with the band 4.1 and ezrin/radixin/moesin homology domain (FERM domain) of FAK. The F2 subdomain of the FAK FERM domain alone is sufficient for Met binding, in which a patch of basic residues (216KAKTLRK222) are critical for the interaction. Met-FAK interaction leads to FAK activation and subsequent contribution to hepatocyte growth factor-induced cell motility and cell invasion. Our results provide evidence that constitutive Met-FAK interaction may be a critical determinant for tumor cells to acquire invasive potential.

[Factors related to sexual dysfunction in patients with cervical cancer].

BACKGROUND: Cervical cancer impacts upon the sex lives of its victims in ways that are more profound than other gynecological cancers. However, no research on sexual dysfunction issues in cervical cancer patients has previously been conducted in Taiwan. PURPOSE: The purposes of this study were to explore sexual dysfunction and related factors in patients diagnosed with cervical cancer. METHODS: The study used a cross-sectional correlation design with a convenience sampling method to recruit 105 patients from a medical center in Northern Taiwan. The structured questionnaire used in this study gathered data on respondent demographics and disease characteristics, and included a Chinese version of the Female Sexual Function Index (FSFI) scale. RESULTS: Respondents noted significant levels of pain triggered by cervical cancer. Lower level of education (below the 9th grade), increased age, lack of religious affiliation and absence of counseling prior to or during therapy were associated with significantly lower sexual dysfunction scores. These factors accounted for 54.60% of variance in sexual dysfunction. CONCLUSION: Our findings should assist healthcare providers to better understand sexual dysfunction in cervical cancer patients, detect those with higher predispositions toward such, and prescribe appropriate rehabilitation therapies to improve sexual enjoyment.

The Conditions Under Which Piracetam Is Used and the Factors That Can Improve National Institute of Health Stroke Scale Score in Ischemic Stroke Patients and the Importance of Previously Unnoticed Factors From a Hospital-Based Observational Study in Taiwan.

This study aimed to explore the associations of piracetam use and the clinical characteristics of NIHSS (National Institute of Health Stroke Scale) changes-the importance of which, as prognosis related factors, was previously unnoticed-and analyze the associations of piracetem with NIHSS changes by stratifying clinical characteristics. This observational retrospective study was conducted by enrolling patients based on 2483 stroke registration data cohorts from a 1200-bed regional Tungs' Taichung MetroHarbor Hospital, located in central Taiwan from 1 January 1 2011 to 31 December 2015. Patients were excluded if they had intravenous a thrombolytic agent within 3 hours of symptoms onset (n = 49), incomplete or erroneous NIHSS scores (n = 953), or transient ischemia stroke (n = 130). Logistic regression model was applied for associating piracetam treatment and clinical characteristics with NIHSS score changes between admission and discharge, and subgroup analysis to assess the conditions under which piracetam can be used. Multivariate analysis revealed NIHSS scores improvement in atrial fibrillation, large-artery atherosclerosis, underweight, current smoker, ex-smoker, and piracetam. Subgroup analysis showed piracetam is beneficial in the following: age ≥75 years olds, males, those of normal weight, those who are obese, ex-smokers, those with hypertension, dyslipidemia, those without diabetes mellitus, nor atrial fibrillation. The selection of the conditions under which piracetam treatment should be given, and clinical characteristics, is important for NIHSS improvement of ischemic stroke patients in Taiwan.

The effects of O-GlcNAc alteration on Alzheimer-like neurodegeneration in SK-N-SH cells.

BACKGROUND: O-GlcNAcylation is a highly dynamic post-translational modification that plays a key role in regulating phosphorylation of protein and cell survival. The proteins O-GlcNAcylation level is regulated dynamically by O-GlcNAc transferase (OGT) and ß-N-acetylglucosaminidase (O-GlcNAcase, OGA). Although previous studies have suggested the role of O-GlcNAcylation in neurodegenerative diseases, the mechanism of O-GlcNAcylation in Alzheimer's disease (AD) remains unclear. METHODS: The decrease of O-GlcNAcylation by alloxan, an OGT inhibitor, and increase by NAG-thiazolines (NAG-Ae), an O-GlcNAcase inhibitor were tested to investigate the effects of O-GlcNAc alteration on AD like neurodegeneration in SK-N-SH cells. RESULTS: The level of O-GlcNAcylation was decreased in alloxan treated cells and increased in NAG-Ae treated cells. Meanwhile, it was observed that both abnormal phosphorylation of NFs in cell bodies and apoptosis induced by alloxan treatment can be resisted by pretreatment or simultaneous treatment with appropriate NAG-Ae. CONCLUSION: These results demonstrated that increasing O-GlcNAc with NAG-Ae protected AD like neurodegeneration from NFs hyperphosphorylation and the cell loss, suggesting the role of O-GlcNAc in the pathogenesis and therapy of AD.

Time-dependent differential expression of long non-coding RNAs following peripheral nerve injury.

Long non-coding RNAs (lncRNAs) are widely accepted as key players in various biological processes. However, the roles of lncRNA in peripheral nerve regeneration remain completely unknown. Thus, in this study, we performed microarray analysis to measure lncRNA expression in the distal segment of the sciatic nerve at 0, 3, 7 and 14 days following injury. We identified 5,354 lncRNAs that were differentially expressed: 3,788 lncRNAs were differentially expressed between days 0 and 3; 3,314 lncRNAs were differentially expressed between days 0 and 7; and 2,400 lncRNAs were differentially expressed between days 0 and 14. The results of RT-qPCR of two dysregulated lncRNAs were consistent with those of microarray analysis. Bioinformatics approaches, including lncRNA classification, gene ontology (GO) analysis and target prediction, were utilized to investigate the functions of these dysregulated lncRNAs in peripheral nerve damage. Importantly, we predicted that several lncRNA-mRNA pairs may participate in biological processes related to peripheral nerve injury. RT-qPCR was performed for the preliminary verification of three lncRNA­mRNA pairs. The overexpression of NONMMUG014387 promoted the proliferation of mouse Schwann cells. Thus, the findings of our study may enhance our knowledge of the role of lncRNAs in nerve injury.

Blockade of v-Src-stimulated tumor formation by the Src homology 3 domain of Crk-associated substrate (Cas).

Crk-associated substrate (Cas) is highly phosphorylated by v-Src and plays a critical role in v-Src-induced cell transformation. In this study, we found that the Src homology (SH) 3 domain of Cas blocked v-Src-stimulated anchorage-independent cell growth, Matrigel invasion, and tumor growth in nude mice. Biochemical analysis revealed that the Cas SH3 domain selectively inhibited v-Src-stimulated activations of AKT and JNK, but not ERK and STAT3. Attenuation of the AKT pathway by the Cas SH3 domain rendered v-Src-transformed cells susceptible to apoptosis. Inhibition of the JNK pathway by the Cas SH3 domain led to suppression of v-Src-stimulated invasion. Taken together, our results indicate that the Cas SH3 domain has an anti-tumor function, which severely impairs the transforming potential of v-Src.

Inhibition of endogenous thyroid hormone receptor-beta and peroxisome proliferator-activated receptor-alpha activities by humic acid in a human-derived liver cell line.

Humic acid (HA), know to be ubiquitous in the natural environment, is present in almost all soil, surface water, and plants. Earlier studies indicate that HA can affect thyroid economy via binding with iodide, inhibiting both thyroid peroxidase and hepatic 5'-deiodinase in rodents. However, the effect of HA, a peroxisome proliferator in rodents, on thyroid hormone receptor (TR) and peroxisome proliferator-activated receptor (PPAR) in human cells has not yet been examined. In this study, we demonstrate that the malic enzyme activity and the transcriptional activities of endogenous TR and PPAR were inhibited after treatment with HA in human hepatocyte Chang liver cell line. Although the protein expression levels of TR-beta, PPAR-alpha and retinoid X receptor-alpha (RXRalpha) were not changed significantly by HA treatment, both the binding abilities of endogenous TR-beta on thyroid hormone response element (TRE) and PPAR-alpha on the PPAR response element (PPRE) were inhibited by HA treatment. The study of the subcellular distribution of HA, relying on the inherent HA fluorescence, showed that HA distributed in the intracellular compartments including cytoplasm and nucleus. The 50% binding inhibition values (CI(50)) of HA on ME-TRE (malic enzyme gene-TRE) and ACOX-PPRE (acylCoA oxidase gene-PPRE) were 19.31 and 19.94 microg/mL, respectively. These results suggest that HA-induced endemic goiter may link in part to the disruption of TRbeta and PPARalpha function in human Chang liver cells. This model may be useful in the investigation of environmental goitrogens.

Simple approach for ultrasensitive electrochemical immunoassay of Clostridium difficile toxin B detection.

Clostridium difficile toxin B (Tcd B), as one of the primary contributing factors to the pathogenesis of C. difficile-associated diseases, has raised serious public concerns due to its virulence, spore-forming ability and persistence with major types of infectious diarrhea diseases, and been used as a potential biomarker in clinical diagnoses. Thus, a simple method for the determination of Tcd B was developed based on a sandwich-type electrochemical immunosensor. Greatly enhanced sensitivity was achieved based on fabricating the immunosensor by layer-by-layer coating carbon nanotubes (MWCNTs), Prussian blue (PB), Chitosan (CS), Glutaraldehyde (GA) composite on the working electrode as well as using graphene oxide (GO) as a nanocarrier in a multienzyme amplification strategy. In comparison with conventional methods, the proposed immunoassay exhibited high sensitivity and selectivity for the detection of Tcd B, providing a better linear response range from 0.003 to 320 ng/mL and a lower limit of detection (LOD) of 0.7 pg/mL (S/N=3) under optimal experimental conditions. The immunosensor exhibited convenience, low cost, rapidity, good specificity, acceptable stability and reproducibility. Moreover, satisfactory results were obtained for the determination of Tcd B in real human stool samples, indicating that the developed immunoassay has the potential to find application in clinical detection of Tcd B and other tumor markers as an alternative approach.

Changes in left atrial functional indexes in ischemic stroke patients.

BACKGROUND: Increased left atrial (LA) size has been proposed as a predictor of multiple adverse cardiovascular events including stroke. LA dysfunction can occur in the absence of increased LA size. However, the relationship between stroke and changes in LA function is not well known. METHODS: Patients with acute ischemic stroke and healthy controls were enrolled prospectively. Stroke patients received standard work-ups to determine the etiology of their strokes. Those patients with significant cardiac arrhythmia and heart failure were excluded. All participants received echocardiography examination. Conventional echocardiographic parameters were calculated and cardiac contractile characteristics of the left atrium and left ventricle were analyzed using vector velocity imaging (VVI) technique. RESULTS: In total, 87 patients with acute ischemic stroke and 20 controls were recruited. The mitral inflow E-wave velocities were lower and A-wave velocities were higher in stroke patients (0.76 ± 0.19 vs. 0.84 ± 0.16, p = 0.048; and 0.97 ± 0.20 vs. 0.76 ± 0.11, p < 0.001 respectively). Stroke patients had a higher active emptying percent of total LA emptying (60.5 ± 19.0%) compared with that in controls (33.5 ± 11.7%, p < 0.001). The minimal LA volume was larger in stroke patients (15.0 ± 10.5 mL) than that in controls (9.9 ± 4.2 mL, p = 0.021), whereas there was no difference in maximal LA volume between stroke patients (37.3 ± 16.5 mL) and controls (33.3 ± 9.9 ml, p = 0.366). The diastolic emptying index of the LA was significantly lower in stroke patients compared with that in controls (61.4 ± 14.6% vs. 70.2 ± 11.0%, p = 0.016). The mitral A-wave velocity and active emptying percent of total LA emptying were significantly higher in all stroke subtypes than those in controls. CONCLUSION: Acute ischemic stroke patients had altered mitral inflow velocities and emptying function of the left atrium. VVI is convenient for quantitative assessment of left atrial volumes and contractile characteristics. Functional changes of LA may occur without significant structural changes. Therefore, the clinical implications of LA functional indexes require further study.

Spontaneous echo contrast in internal jugular veins: a probable indicator for systemic inflammation and a prothrombotic state.

The hypothesis that spontaneous echo contrast (SEC) in the internal jugular vein (IJV) is a clinical indicator for systemic inflammation and thrombogenesis is investigated in this study. Fifty-two patients with cardiovascular diseases and 25 nondiseased subjects were evaluated. SEC was observed in 96 of 154 IJVs. The visual grading of SEC showed good interobserver agreement on SEC grades (κ value: 0.846, p < 0.001). Generalized estimating equations analysis was used for univariate and multivariate analysis. Univariate analysis showed that peak flow velocity in corresponding IJV (coefficient -0.001 [95% CI -0.019, -0.001], p = 0.031), jugular venous reflux (JVR, -0.010 [-0.019, -0.001], p = 0.002), plasma levels of fibrinogen (0.464 [0.208, 0.719], p < 0.001) and hs-C-reactive protein (hs-CRP) (0.479 [0.184, 0.774], p = 0.001) and previous history of ischemic stroke (0.779 [0.139, 1.417]; p = 0.017) correlated with the grades of SEC in IJV. Increased plasma levels of fibrinogen and hs-CRP, previous ischemic stroke, lower peak velocity in corresponding IJV and JVR were also independent predictors for the higher grades of SEC in IJV in multivariate regression analysis. SEC in IJV could be evaluated easily and semiquantitatively. SEC in IJVs could be a putative marker of cerebral circulation disturbance and an indicator of systemic inflammatory or prothrombotic state.