Surface-Activated Ti3C2Tx Adsorption of Acetylene Black Coupled with Polyaniline as a Signal Tag for the Detection of the ESAT-6 Antigen of Mycobacterium tuberculosis.

Early secretory antigenic target-6 (ESAT-6) is regarded as the most immunogenic protein produced by Mycobacterium tuberculosis, whose detection is of great clinical significance for tuberculosis diagnosis. However, the detection of the ESAT-6 antigen has been hampered by the expensive cost and complex experimental procedures, resulting in low sensitivity. Herein, we developed a titanium carbide (Ti3C2Tx)-based aptasensor for ESAT-6 detection utilizing a triple-signal amplification strategy. First, acetylene black (AB) was immobilized on Ti3C2Tx through a cross-linking reaction to form the Ti3C2Tx-AB-PAn nanocomposite. Meanwhile, AB served as a conductive bridge, and Ti3C2Tx can synergistically promote the electron transfer of PAn. Ti3C2Tx-AB-PAn exhibited outstanding conductivity, high electrochemical signals, and abundant sites for the loading of ESAT-6 binding aptamer II (EBA II) to form a novel signal tag. Second, N-CNTs were adsorbed on NiMn layered double hydride (NiMn LDH) nanoflowers to obtain NiMn LDH/N-CNTs, exhibiting excellent conductivity and preeminent stability to be used as electrode modification materials. Third, the biotinylated EBA (EBA I) was immobilized onto a streptavidin-coated sensing interface, forming an amplification platform for further signal enhancement. More importantly, as a result of the synergistic effect of the triple-signal amplification platform, the aptasensor exhibited a wide detection linear range from 10 fg mL-1 to 100 ng mL-1 and a detection limit of 4.07 fg mL-1 for ESAT-6. We envision that our aptasensor provides a way for the detection of ESAT-6 to assist in the diagnosis of tuberculosis.

Identification of diagnostic model in heart failure with myocardial fibrosis and conduction block by integrated gene co-expression network analysis.

BACKGROUND: Despite the advancements in heart failure(HF) research, the early diagnosis of HF continues to be a challenging issue in clinical practice. This study aims to investigate the genes related to myocardial fibrosis and conduction block, with the goal of developing a diagnostic model for early treatment of HF in patients. METHOD: The gene expression profiles of GSE57345, GSE16499, and GSE9128 were obtained from the Gene Expression Omnibus (GEO) database. After merging the expression profile data and adjusting for batch effects, differentially expressed genes (DEGs) associated with conduction block and myocardial fibrosis were identified. Gene Ontology (GO) resources, Kyoto Encyclopedia of Genes and Genomes (KEGG) resources, and gene set enrichment analysis (GSEA) were utilized for functional enrichment analysis. A protein-protein interaction network (PPI) was constructed using a string database. Potential key genes were selected based on the bioinformatics information mentioned above. SVM and LASSO were employed to identify hub genes and construct the module associated with HF. The mRNA levels of TAC mice and external datasets (GSE141910 and GSE59867) are utilized for validating the diagnostic model. Additionally, the study explores the relationship between the diagnostic model and immune cell infiltration. RESULTS: A total of 395 genes exhibiting differential expression were identified. Functional enrichment analysis revealed that these specific genes primarily participate in biological processes and pathways associated with the constituents of the extracellular matrix (ECM), immune system processes, and inflammatory responses. We identified a diagnostic model consisting of 16 hub genes, and its predictive performance was validated using external data sets and a transverse aortic coarctation (TAC) mouse model. In addition, we observed significant differences in mRNA expression of 7 genes in the TAC mouse model. Interestingly, our study also unveiled a correlation between these model genes and immune cell infiltration. CONCLUSIONS: We identified sixteen key genes associated with myocardial fibrosis and conduction block, as well as diagnostic models for heart failure. Our findings have significant implications for the intensive management of individuals with potential genetic variants associated with heart failure, especially in the context of advancing cell-targeted therapy for myocardial fibrosis.

Identification of aneuploidy-related gene signature to predict survival in head and neck squamous cell carcinomas.

BACKGROUND: To parse the characteristics of aneuploidy related riskscore (ARS) model in head and neck squamous cell carcinomas (HNSC) and their predictive ability on patient prognosis. METHODS: Molecular subtyping of HNSC specimens was clustered by Copy Number Variation (CNV) data from The Cancer Genome Atlas (TCGA) dataset applying consistent clustering, followed by immune condition evaluation, differentially expressed genes (DEGs) analysis and DEGs function annotation. Weighted gene co-expression network analysis (WGCNA), protein-protein interaction, Univariate Cox regression analysis, least absolute shrinkage and selection operator (LASSO) and stepwise multivariate Cox regression analysis were implemented to construct an ARS model. A nomogram for clinic practice was designed by rms package. Immunotherapy evaluation and drug sensitivity prediction were also carried out. RESULTS: We stratified HNSC patients into three different molecular subgroups, with the best prognosis in C1 cluster among 3 clusters. C1 cluster displayed greatest immune infiltration status. The most DEGs between C1 and C2 groups, mainly enriched in cell cycle and immune function. We constructed a nine-gene ARS model (ICOS, IL21R, CCR7, SELL, CYTIP, ZAP70, CCR4, S1PR4 and CD79A) that effectively differentiates between high- and low-risk patients. Patients in low ARS group showed a higher sensitivity to immunotherapy. A nomogram built by integrating ARS and clinic-pathological characteristics helped predict clinic survival benefit. Drug sensitivity evaluation found that 4/9 inhibitor drugs (MK-8776, AZD5438, PD-0332991, PHA-665752) acted on the cell cycle. CONCLUSIONS: We classified 3 molecular subtypes for HNSC patients and established an ARS prognostic model, which offered a prospective direction for prognosis in HNSC.

Smartphone and paper-based device for glucose monitoring using acetylene black-hemin nanozyme as catalyst.

Glucose management is an important part of disease control for diabetes patients, thus the development of a rapid and real-time point of care testing (POCT) device for monitoring blood glucose is of great significance. In this work, a paper-based analytical device (PAD) is constructed by combining acetylene black (AB)-hemin complex modified filter paper as sensing platform with a smartphone as signal detector. Large specific surface area of AB decreases the self-associate and aggregate of hemin in aqueous solution, resulting in improved peroxidase-like activity of hemin. Compared with graphene oxide supported hemin, AB-hemin exhibits superior signal response on paper. Glucose oxidase (GOx) catalyzes the conversion of blood glucose to hydrogen peroxide, and then AB-hemin complex catalyzes the oxidation of colorless 3,3',5,5'-tetramethylbenzidine (TMB) to blue TMB oxidized products (TMB+) in the presence of hydrogen peroxide, thus achieving the visual detection of blood glucose. In optimal conditions, PAD provides an applicable linear range from 0.2 mM to 30 mM and a low limit of detection (LOD) (0.06 mM). Notably, the detection accuracy of the developed paper-based sensor is in good agreement with that of the commercially available blood glucose meter (p > 0.05). Moreover, the proposed PAD presents high recoveries from 95.4% to 112% (RSD ≤ 3.2%), and therefore holds great potential for glucose monitoring and diabetes diagnosis.

An enzymatic activity regulation-based clusterzyme sensor array for high-throughput identification of heavy metal ions.

The accurate identification and sensitive quantification of heavy metal ions are of great significance, considering that pose a serious threat to environment and human health. Most array-based sensing platforms, to date, utilize nanozymes as sensing elements, but few studies have explored the application of the peroxidase-like activity of clusterzymes in identification of multiple analytes. Herein, for the first time, we developed a clusterzyme sensor array utilizing gold nanoclusters (AuNCs) as sensing elements for five heavy metal ions identification including Hg2+, Pb2+, Cu2+, Cd2+ and Co2+. The heavy metal ions can differentially regulate the peroxidase-like activity of AuNCs, and that can be converted into colorimetric signals with 3,3',5,5'-tetramethylbenzidine (TMB) as the chromogenic substrate. Subsequently, the generated composite responses can be interpreted by combining pattern recognition algorithms. The developed clusterzyme sensor array can identify five heavy metal ions at concentrations as low as 0.5 µM and their multi-component mixtures. Especially, we demonstrated the successful identification of multiple heavy metal ions in tap water and traditional Chinese medicine, with an accuracy of 100% in blind test. This study provided a simple and effective method for identification and quantification of heavy metal ions, rendering a promising technique for environmental monitoring and drug safety assurance.

Case report: Early thrombosis in left atrial during transcatheter closure of ASD in a child with favorable outcome after use of GPIIb/IIIa receptor antagonist and heparin.

Background: Acute thrombus in atrial septal defect occluders is a rare complication that requires aggressive, effective, and safe management. Tirofiban, a platelet glycoprotein IIb/IIIa receptor antagonist, is widely used for the management of thromboembolic diseases, such as coronary heart disease and stroke. To date, there is no report using the GPIIb/IIIa receptor antagonist tirofiban for the management of ASD closure-related thrombosis in children. Case presentation: Herein, we reported a case of a 5-year-old girl with ASD who presented with acute thrombus on the left disc of the occluder device immediately after transcatheter closure of ASD. The thrombus was successfully dissolved 24 h after a combined infusion of heparin and tirofiban, followed by 1 months of aspirin and clopidogrel and 5 months of aspirin alone. No thromboembolism or hemorrhage events occurred during follow-up for more than 2 years. Conclusion: The continuous infusion of GPIIb/IIIa receptor antagonist tirofiban combined with heparin may have beneficial effects for the management of thrombosis during ASD closure procedure.

Current career situations of Chinese pharmacovigilance professionals working for pharmaceutical companies: an exploratory survey.

BACKGROUND: Pharmacovigilance in China has experienced rapid development in the past 30 years. The implementation of Good Pharmacovigilance Practice in China since the end of 2021 heralds a new era of pharmacovigilance affairs, which puts forward higher requirements for the quantity and quality of pharmacovigilance personnel. This study aimed to preliminarily explore the current career situations of pharmacovigilance professionals working in China for pharmaceutical companies. METHODS: A questionnaire was adapted from research in the USA and Europe with the help of several pharmacovigilance experts. Snowball sampling was used to conduct an exploratory survey to obtain the frequency of basic demographic information, work status, and career expectations of pharmacovigilance professionals working for pharmaceutical companies. RESULTS: The personnel engaged in pharmacovigilance work for pharmaceutical companies were mainly medical or pharmaceutical undergraduates within 3 years of graduation. Their work intensity and pressure were relatively high. The training provided by their universities and enterprises could not well meet their needs to improve their job competence. Although they were optimistic about pharmacovigilance and will not change their career, most of them were planning to change their employers. CONCLUSION: There was a gap between the demand and supply of pharmacovigilance personnel. Relevant regulatory authorities and industry associations should guide higher education institutions to collaborate with pharmacovigilance specialists to strengthen pharmacovigilance education for medical or pharmaceutical students, on the basis of which pharmacovigilance certification courses and continuing education courses can be developed. Meanwhile, pharmaceutical enterprises should consider reasonably adjusting work intensity and income to avoid a high turnover rate.

A new biomimetic nanozyme of hemin/graphdiyne oxide with superior peroxidase-like activity for colorimetric bioassays.

Graphdiyne oxide (GDYO) is a novel type of two-dimensional carbon allotrope nanomaterial consisting of a large conjugated system and excellent chemical stability. To date, application of GDYO as a nanozyme in biosensing has been rarely reported. In this study, a novel ultrasensitive colorimetric bioassay was constructed using a hemin/GDYO nanocomposite (H/GDYO) as a new nanozyme with superior peroxidase-like activity for the detection of H2O2 and glucose. It was discovered that H/GDYO exhibited 6-fold higher peroxidase-like activity than pure hemin. Catalytic kinetic analysis showed that H/GDYO had a much higher affinity for H2O2 and glucose than that of hemin. The designed colorimetric bioassay displayed excellent sensitivity for H2O2 and glucose detection with a wide linear range of 0.015-0.5 mM and 0.1-10 mM, respectively, while the limit of detection (LOD) was as low as 4.39 µM and 38 µM, respectively. Moreover, it was successfully applied for the analysis of H2O2 in milk and glucose in real human serum samples with acceptable recoveries. Importantly, the developed colorimetric bioassay shows good agreement with the results obtained from a commercial blood glucose meter. We believe that the proposed method could provide a promising prospect for medical diagnosis and biotechnology.

Electrochemical aptasensor for ultrasensitive detection of lipopolysaccharide using silver nanoparticles decorated titanium dioxide nanotube/functionalized reduced graphene oxide as a new redox nanoprobe.

A novel and relatively simple signal-off electrochemical aptasensor was constructed for highly sensitive detection of lipopolysaccharide (LPS). For the first time, silver nanoparticles (AgNPs) decorated titanium dioxide nanotube (TNT) was conjugated with polydiallyldimethylammonium chloride (PDDA) functionalized reduced graphene oxide (rGO) to form a new nanohybrid of Ag-TNT/P-rGO. This nanohybrid with a large specific surface area exhibited excellent electrochemical activity, which not only served as the sensing platform to immobilize LPS binding aptamer (LBA) but was also employed as the redox probe to monitor the change of the electrochemical signal. The electrochemical signal responses were measured by cyclic voltammetry (CV) in the potential range -0.3 to 0.5 V at a scan rate of 0.1 V/s. The proposed aptasensor exhibited acceptable stability, reproducibility, and specificity for LPS detection with a wide linear range from 17 fg/mL to 100 ng/mL. The limit of detection (LOD) was 5 fg/mL. Furthermore, the prepared aptasensor showed acceptable recovery ranging from 96% to 103%, and the RSD varied between 1.4% and 8.5% for determining LPS in real samples.Graphical abstract.

A target-induced amperometic aptasensor for sensitive zearalenone detection by CS@AB-MWCNTs nanocomposite as enhancers.

In this research, a novel signal-on aptasensor for highly sensitive detection of zearalenone (ZEN) was reported based on target-induced amplification strategy. Specifically, chitosan functionalized acetylene black and multi-walled carbon nanotubes (CS@AB-MWCNTs) nanocomposite with large specific surface area and excellent conductivity was synthesized and served as the sensing platform. In addition, carboxylated graphene oxide-labeled ZEN binding aptamer (CGO-ZBA) would specifically recognized with ZEN to detach from the electrode, allowing the electrochemical signal of [Fe(CN)6]3-/4- increased more obviously. Under the optimal conditions, the proposed aptasensor exhibited exceptional detection performances for ZEN with a linear range from 10 fg mL-1 to 1 ng mL-1 and a low limit of detection of 3.64 fg mL-1. Given its great sensitivity, excellent selectivity, satisfactory stability and reproducibility, this method would provide a promising application for ZEN and other biomolecules by replacing the corresponding nucleicacidsequences.

An efficient electrochemical assay for miR-3675-3p in human serum based on the nanohybrid of functionalized fullerene and metal-organic framework.

Idiopathic pulmonary fibrosis (IPF) is an interstitial lung disease with unclear pathogenesis, for which diagnosis has been a great challenge. Recent researches have revealed that miR-3675-3p is a promising biomarker for IPF diagnosis. Herein, the present work describes a novel electrochemical microRNA biosensor for rapid and sensitive detection of miR-3675-3p based on multiple signal amplification strategies. First of all, fullerene (C60) is doped with poly(amidoamine) (PAMAM)-functionalized metal-organic framework (MOF) to form a new nanohybrid of C60@PAMAM-MOF, which exhibits more remarkable redox activity compared with the other two synthesized C60-based nanohybrids when triggered by tetraoctylammonium bromide (TOAB). C60@PAMAM-MOF also possesses a large specific surface area and abundant amino groups to anchor Au nanoparticles (AuNPs) for the immobilization of signal probe (SP) to form tracer label and enhance the electrochemical response signal. In addition, core@shell Au-Pt nanoparticles (Au@PtNPs) are absorbed on chitosan-acetylene black (CS-AB) to act as sensing platform, which can promote electron transfer and increase the loading of capture probe (CP). Under optimum conditions, the proposed biosensor displays a wide linear range for miR-3675-3p from 10 fM to 10 nM, with a limit of detection (LOD) as low as 2.99 fM. More significantly, this biosensor shows a lower LOD and wider linear range than that of qRT-PCR, and its trial application in human serum shows favorable results, which exhibits a promising prospect for IPF diagnosis.

Altered gut microbiota correlated with systemic inflammation in children with Kawasaki disease.

Kawasaki disease (KD) is a multi-systemic vasculitis of unknown etiology that occurs mainly in children, and the disturbance of gut microbiota is generally believed to cause a hyperimmune reaction triggering KD. The aim of the study was to investigate the alterations in the fecal microbiota and assess its relationship with systemic inflammation. Totally 30 KD children were enrolled and followed up for 6 months, with another group of 30 age- and sex-matched healthy children as controls. Phylotype profiles of fecal microbial communities were analyzed using 16S rRNA gene sequencing. Serum inflammatory markers were detected by flow cytometer. We showed that KD children exhibited a significant reduction in fecal microbial diversity in the acute phase compared with the healthy controls. Enterococcus, Acinetobacter, Helicobacter, Lactococcus, Staphylococcus and Butyricimonas in acute KD children were significantly higher than the healthy children. Levels of systemic inflammation biomarkers, including IL-2, IL-4, IL-6, IL-10, TNF-α, and INF-γ, were significantly elevated in the acute KD children. Altered microbiota genera Enterococcus and Helicobacter abundances were shown to be correlated positively with IL-6, which were never previously reported in KD. This study suggested that gut microbiota alteration is closely associated with systemic inflammation, which provides a new perspective on the etiology and pathogenesis of KD.

Tumour necrosis factor-α and myoglobin associated with the recovery time of coronary artery lesions in Kawasaki disease patients.

AIM: To assess the relationship between clinical parameters and medium term recovery time of coronary artery lesions (CALs). METHODS: In total, 344 Kawasaki disease patients were screened and 311 Kawasaki disease patients were included and followed-up for the next 2 years. Clinical records, clinical parameters and inflammatory biomarkers were collected for all subjects. RESULTS: Tumour necrosis factor (TNF)-α and myoglobin (MYO) levels in patients without recovery from CALs were significantly higher than those without CALs and with recovery from CALs. Kaplan-Meier survival analysis showed that in the high-TNF-α group, the estimated median time to recovery (5.0 months, 95% confidence interval (CI) 1.436-8.564) is significantly longer than the low-TNF-α group (2.00 months, 95% CI: 0.633-3.367, P = 0.044). Also, the estimated median time (5.0 months, 95% CI: 1.836-8.164) in the high-MYO group is significantly longer than the low-MYO group (2.00 months, 95% CI: 0.405-3.595, P = 0.002). Cox regression analysis showed independent factors for recovery of CALs included age, left coronary artery to aortic annulus ratio, TNF-α and MYO levels. CONCLUSIONS: These findings suggest that clinical parameters such as age, left coronary artery to aortic annulus ratio, TNF-α and MYO levels associate with medium term recovery time of CALs and could help in the design of a clinical strategy for the surveillance and prevention of late cardiovascular events.

Baicalin and its nanoliposomes ameliorates nonalcoholic fatty liver disease via suppression of TLR4 signaling cascade in mice.

As a natural flavonoid compound, baicalin(BA)has been reported to exhibit hepatoprotective and anti-inflammatory properties. However, the characteristic of poor solubility and low bioavailability greatly limits its application. In addition, the effects and underlying mechanisms of BA in nonalcoholic fatty liver disease (NAFLD) remain elusive. In this study, Methionine and choline deficient diet (MCD)-induced NAFLD mice were treated with baicalin or baicalin-loaded nanoliposomes (BA-NL), then hepatic histopathological changes, biochemical parameters and inflammatory molecules were observed. We found that mice in MCD group showed significant increases in plasma transaminase, hepatocyte apoptosis, hepatic lipid accumulation, liver fibrosis, and infiltration of neutrophils and macrophages compared with control group, however, BA and BA-NL markedly attenuated MCD-induced the above changes. Besides, further analysis indicated that BA and BA-NL also inhibited the up-regulation of toll-like receptor 4 (TLR4) signal and the production of inflammatory mediators in MCD mice. Importantly, BA-NL was found to be more effective than baicalin on MCD-induced NAFLD in mice. These data suggested that BA and its nanoliposomes BA-NL could effectively protect mice against MCD-induced NAFLD, which might be mediated through inhibiting TLR4 signaling cascade.

[Expression of Nod-like receptor protein 3 inflammasome in peripheral blood mononuclear cells of children with Kawasaki disease in the acute stage].

OBJECTIVE: To study the association of Nod-like receptor protein 3 (NLRP3) inflammasome with inflammatory response in the acute stage and coronary artery lesion (CAL) in children with Kawasaki disease (KD). METHODS: A total of 42 children with KD who were hospitalized from January to October 2017 were enrolled as the KD group, among whom 9 had CAL (CAL group) and 33 had no CAL (NCAL group). Fifteen age- and gender-matched children with pneumonia and pyrexia were enrolled as the pneumonia-pyrexia group. Fifteen healthy children were enrolled as the healthy control group. Real-time PCR was used to measure the mRNA expression of NLRP3 inflammasome (NLRP3, ASC and caspase-1) in peripheral blood mononuclear cells. The Spearman rank correlation test was used to investigate the correlation of NLRP3 mRNA expression with serum levels of C-reactive protein, erythrocyte sedimentation rate, interleukin-6, interleukin-1ß, procalcitonin, albumin and prealbumin. RESULTS: The KD group had significantly higher mRNA expression of NLRP3, ASC and caspase-1 in the acute stage than the pneumonia-pyrexia and healthy control groups (P<0.05). The CAL group had significantly higher mRNA expression of NLRP3 than the NCAL group (P<0.05). NLRP3 mRNA expression was correlated with C-reactive protein, interleukin-6, interleukin-1ß, and prealbumin levels in children with KD in the acute stage (rs=0.449, 0.376, 0.427, and -0.416 respectively; P<0.05). CONCLUSIONS: NLRP3 inflammasome may participate in inflammatory response in the acute stage and the development of CAL in children with KD.

[Role of apoptosis signal-regulating kinase 1 in left ventricular remodeling in mice].

OBJECTIVE: To study the changes and significance of apoptosis signal-regulating kinase 1 (ASK1) in left ventricular remodeling in FVB/N mice. METHODS: A total of 54 FVB/N mice were randomly divided into 4 groups: 0 d group with 8 mice, 7 d group with 10 mice, 14 d group with 16 mice, and 21 d group with 20 mice. A model of cardiac remodeling was established by intraperitoneal injection of isoproterenol (ISO) at a daily dose of 30 mg/kg, and the 7 d, 14 d, and 21 d groups were injected for 7, 14, and 21 consecutive days respectively. The 0 d group was given intraperitoneal injection of an equal volume of normal saline. Echocardiography was used to measure left ventricular posterior wall thickness at end diastole (dLVPW) and the ratio of heart weight to tibia length (HW/TL) was measured. Hematoxylin-eosin staining was used to measure left ventricular myocardial fiber diameter. Picric-Sirius red staining was used to measure myocardial collagen deposition area in the left ventricle. Quantitative real-time PCR was used to measure the mRNA expression of ASK1, type I collagen (collagen I), and B-type natriuretic peptide (BNP). The mortality rate was observed for each group. RESULTS: There were gradual increases in HW/TL, myocardial fiber diameter, and dLVPW after 0, 7, and 14 days of ISO injection (P<0.05). There were no significant changes in HW/TL ratio and dLVPW from days 14 to 21 of ISO injection (P>0.05), while there was a significant reduction in myocardial fiber diameter (P<0.05), which was similar to the value on day 7 (P>0.05). There were significant increases in myocardial collagen deposition area and the mRNA expression of collagen I, ASK1, and BNP after 0, 7, 14, and 21 days of ISO injection, which reached the peaks on day 21 (P<0.01). The mRNA expression of ASK1 was positively correlated with myocardial collagen deposition area and the mRNA expression of collagen I and BNP and had a weak correlation with HW/TL, myocardial fiber diameter, and dLVPW. There was a significant increase in the mortality rate of the mice over the time of ISO injection. CONCLUSIONS: The expression of ASK1 in the myocardium is closely associated with left ventricular remodeling. The increase of ASK1 expression may lead to the aggravation of left ventricular remodeling, and the mechanism of which needs further study.

Risk Factors for New-Onset Diabetes Mellitus after Heart Transplantation in Chinese Patients: A Single Center Experience.

BACKGROUND: New-onset diabetes after transplantation -(NODAT) is a frequent complication after heart transplantation (HT) and is associated with graft loss and patient survival. OBJECTIVES: The aim of this study was to identify the incidence and associated factors contributing to NODAT in Chinese heart transplant recipients. METHODS: Adult patients without diabetes mellitus before HT were enrolled in this study. NODAT was diagnosed according to the criteria recommended by the American Diabetes Association. The cumulative incidence was determined at 3, 6, and 12 months, respectively. The risk factors of NODAT were estimated by logistic regression analysis. RESULTS: A total of 154 adults who first received HT were included. Among them, 50 (32.5%) recipients were diagnosed with NODAT after a median follow-up time of 611 days. The cumulative incidence of NODAT was 27.3% at 3 months, 29.9% at 6 months, and 30.5% at 12 months, respectively. Independent risk factors for NODAT included age ≥45 years (OR 3.82, 95% CI 1.57-9.31; p = 0.003), hypertension (OR 3.28, 95% CI 1.17-9.20; p= 0.024), and transient hyperglycemia (OR 12.13, 95% CI 3.35-43.92; p < 0.001). Moreover, recipients treated with both acarbose and insulin for transient hyperglycemia had a significantly higher prevalence of NODAT than those without any anti-diabetic agents (OR 5.35, 95% CI 1.21-23.64; p = 0.027). CONCLUSIONS: Age ≥45 years, hypertension, transient hyperglycemia, and associated treatment strategies are imperative to identify recipients at high risk of developing -NODAT.

An aptamer based voltammetric biosensor for endotoxins using a functionalized graphene and molybdenum disulfide composite as a new nanocarrier.

Lipopolysaccharides (LPS), known as endotoxins, can cause a strong inflammatory response and lead to multiple organ failure in severe cases. This work reports a simple label-free voltammetric aptasensor for highly sensitive determination of LPS using a polyethyleneimine (PEI) functionalized reduced graphene oxide (rGO) and molybdenum disulfide (MoS2) composite (PEI-rGO-MoS2) as a new nanocarrier for electroactive toluidine blue (TB). The PEI-rGO-MoS2 nanocomposite with high electrical conductivity and large specific surface area can greatly increase the loading of TB and facilitate electron transfer from TB to an electrode. Then gold nanoparticles (AuNPs) were utilized to immobilize a thiolated LPS binding aptamer (LBA), which not only exhibited excellent biocompatibility, but also significantly amplified the electrochemical signal of TB. The proposed aptasensor exhibited high sensitivity for LPS and showed a wide linear range from 5.0 × 10-5 ng mL-1 to 2.0 × 102 ng mL-1 with a low limit of detection (LOD) of 3.01 × 10-5 ng mL-1, which overcame the shortcomings of traditional detection methods and achieved fast and accurate detection of LPS. Moreover, it exhibited excellent recovery and specificity upon spiking LPS in serum samples, indicating that this method has promising application in the field of trace analysis of LPS in clinical detection.

Adherence to Adjuvant Imatinib Therapy in Patients with Gastrointestinal Stromal Tumor in Clinical Practice: A Cross-Sectional Study.

BACKGROUND: Adherence to imatinib therapy has been significantly associated with disease progression and direct medical costs in gastrointestinal stromal tumor (GIST) patients. However, adherence to oral anticancer drugs is frequently hindered by the influence of various factors. The aim of this study was to evaluate the prevalence of imatinib adherence and its influencing factors among GIST patients in the adjuvant setting. METHODS: Adherence of GIST patients (receiving imatinib for ≥1 month) was assessed using the 8-item Morisky Medication Adherence Scale (MMAS), with a score <8 indicating nonadherence. Quality of life and social support were evaluated by the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C30 (EORTC QLQ C30) and Social Support Rating Scale (SSRS). Factors associated with nonadherence were identified by multivariate logistic regression analysis. Imatinib plasma concentrations were determined and compared between adherent and nonadherent groups. RESULTS: A total of 158 GIST patients were enrolled, 92 (58.2%) patients were considered nonadherent. Intentional nonadherence, especially feeling hassled by treatment plan (34.2% of patients), was common. In the multivariate logistic regression analysis, gender (OR 2.68, 95% CI 1.33-5.41; p = 0.0058), place of residence (OR 3.20, 95% CI 1.39-7.35; p = 0.0061), and global health status (OR 1.02, 95% CI 1.00-1.04; p = 0.0378) were significantly associated with nonadherence. Moreover, imatinib plasma concentrations in nonadherent patients were significantly lower than that in the good adherence group (p = 0.0338). CONCLUSIONS: Poor adherence to imatinib is a notable problem in Chinese GIST patients in the adjuvant therapy setting. The predominant indicators of nonadherence in this study were gender (female), living in a rural area, and harboring a low global health status score. These indicators may aid clinicians in determining where increased efforts in promoting adherence may be beneficial.

Prevalence and Risk Factors of Immunosuppressant Nonadherence in Heart Transplant Recipients: A Single-Center Cross-Sectional Study.

BACKGROUND: Immunosuppressant nonadherence (INA) has been shown to affect outcomes after solid organ transplantation. The aim of the present study was to determine the prevalence of INA in heart transplant recipients and the associated risk factors of INA. METHODS: Adult heart transplant recipients who firstly received heart transplantation (discharged for at least 3 months) were consecutively enrolled. Immunosuppressant adherence was assessed using the Basel Assessment of Adherence with Immunosuppressive Medication Scale (BAASIS). INA was categorized into five domains of contributing factors (socio-demographic factors, transplant-related factors, healthcare system access factors, post-transplant treatment-related factors, and patient-related psychosocial factors). These factors were compared between adherent and nonadherent patients. The risk factors of INA were investigated by logistic regression analysis. RESULTS: A total of 168 heart recipients were ultimately included. Among them, 69 (41.1%) recipients were revealed to be nonadherent. Logistic regression analysis indicated that INA was associated with monthly income<3000 Chinese Yuan (CNY) (OR, 3.11; 95% CI, 1.58-6.12; p=0.001), number of prescribed concomitant drugs (OR, 1.23; 95% CI, 1.12-1.50; p=0.003) and concerns about immunosuppressants (OR, 1.09; 95% CI, 1.01-1.18; p=0.031). CONCLUSIONS: Heart recipients had a high prevalence of INA. Lower income, greater number of prescribed concomitant drugs, and more concerns about immunosuppressants correlated most with timing nonadherence and taking nonadherence among heart recipients. These findings will be helpful to intervene on and prevent future INA of heart recipients.