Glutathione­iron hybrid nanozyme-based colorimetric sensor for specific and stable detection of thiram pesticide on fruit juices.

Given the potential dangers of thiram to food safety, constructing a facile sensor is significantly critical. Herein, we presented a colorimetric sensor based on glutathione­iron hybrid (GSH-Fe) nanozyme for specific and stable detection of thiram. The GSH-Fe nanozyme exhibits good peroxidase-mimicking activity with comparable Michaelis constant (Km = 0.551 mM) to the natural enzyme. Thiram pesticides can specifically limit the catalytic activity of GSH-Fe nanozyme via surface passivation, causing the change of colorimetric signal. It is worth mentioning that the platform was used to prepare a portable hydrogel kit for rapid qualitative monitoring of thiram. Coupling with an image-processing algorithm, the colorimetric image of the hydrogel reactor is converted into the data information for accurate quantification of thiram with a detection limit of 0.3 µg mL-1. The sensing system has good selectivity and high stability, with recovery rates in fruit juice samples ranging from 92.4% to 106.9%.

SLC27A2 is a potential immune biomarker for hematological tumors and significantly regulates the cell cycle progression of diffuse large B-cell lymphoma.

BACKGROUND: Research on the fatty acid metabolism related gene SLC27A2 is currently mainly focused on solid tumors, and its mechanism of action in hematological tumors has not been reported. METHOD: This study aims to explore the pathological and immune mechanisms of the fatty acid metabolism related gene SLC27A2 in hematological tumors and verify its functional role in hematological tumors through cell experiments to improve treatment decisions and clinical outcomes of hematological tumors. RESULT: This study identified the fatty acid metabolism related gene SLC27A2 as a common differentially expressed gene between DLBCL and AML. Immune microenvironment analysis showed that SLC27A2 was significantly positively correlated with T cell CD4 + , T cell CD8 + , endothelial cells, macrophages, and NK cells in DLBCL. In AML, there is a significant negative correlation between SLC27A2 and B cells, T cell CD8 + , and macrophages. SLC27A2 participates in the immune process of hematological tumors through T cell CD8 + and macrophages. The GESA results indicate that high expression of SLC27A2 is mainly involved in the fatty acid pathway, immune pathway, and cell cycle pathway of DLBCL. The low expression of SLC27A2 is mainly involved in the immune pathway of AML. Therefore, SLC27A2 is mainly involved in the pathological mechanisms of hematological tumors through immune pathways, and cell experiments have also confirmed that SLC27A2 is involved in the regulation of DLBCL cells. CONCLUSION: In summary, our research results comprehensively report for the first time the mechanism of action of SLC27A2 in the immune microenvironment of DLBCL and AML, and for the first time verify the cycle and apoptotic effects of the fatty acid related gene SLC27A2 in DLBCL cells through cell experiments. Research can help improve the treatment of AML and DLBCL patients.

Dynamic variation in the aroma characteristics of Rhus chinensis honey at different stages after capping.

The ripening characteristics after capping of honey are favourable for improving its quality. However, research on the variation and formation of aroma characteristics of honey in this process is lacking. Therefore, the present study was carried out with different stages of Rhus chinensis honeys (RCHs) after capping and identified 192 volatiles with varying levels of concentration. "Fruity" was the main aroma characteristic of RCHs at different stages after capping, mainly contributed by (E)-ß-damascenone. Methyl salicylate might be a potential indicator for differentiating RCHs at different stages after capping. The metabolic pathway analyses revealed that the aroma compounds in RCHs undergo transformation at different stages after capping, which subsequently affects its aroma characteristics formation. This work is the first to study the dynamic changes in honey aroma characteristics after capping from multiple perspectives, and the results are of great significance for understanding the aroma characteristics after capping and quality control of honey.

Tanshinone IIA positively regulates the Keap1-Nrf2 system to alleviate pulmonary fibrosis via the sestrin2-sqstm1 signaling axis-mediated autophagy.

BACKGROUND: Activation of myofibroblasts, linked to oxidative stress, emerges as a pivotal role in the progression of pulmonary fibrosis (PF). Our prior research has underscored the therapeutic promise of tanshinone IIA (Tan-IIA) in mitigating PF by enhancing nuclear factor-erythroid 2-related factor 2 (Nrf2) activity. Nevertheless, the molecular basis through which Tan-IIA influences Nrf2 activity has yet to be fully elucidated. METHODS: The influence of Tan-IIA on PF was assessed in vivo and in vitro models. Inhibitors, overexpression plasmids, and small interfering RNA (siRNA) were utilized to probe its underlying mechanism of action in vitro. RESULTS: We demonstrate that Tan-IIA effectively activates the kelch-like ECH-associated protein 1 (Keap1)-Nrf2 antioxidant pathway, which in turn inhibits myofibroblast activation and ameliorates PF. Notably, the stability and nucleo-cytoplasmic shuttling of Nrf2 is shown to be dependent on augmented autophagic flux, which is in alignment with the observation that Tan-IIA induces autophagy. Inhibition of autophagy, conversely, fosters the activation of extracellular matrix (ECM)-producing myofibroblasts. Further, Tan-IIA initiates an autophagy program through the sestrin 2 (Sesn2)-sequestosome 1 (Sqstm1) signaling axis, crucial for protecting Nrf2 from Keap1-mediated degradation. Meanwhile, these findings were corroborated in a murine model of PF. CONCLUSION: Collectively, we observed for the first time that the Sqstm1-Sesn2 axis-mediated autophagic degradation of Keap1 effectively prevents myofibroblast activation and reduces the synthesis of ECM. This autophagy-dependent degradation of Keap1 can be initiated by the Tan-IIA treatment, which solidifies its potential as an Nrf2-modulating agent for PF treatment.

Carboxyl-terminal sequences in APOA5 are important for suppressing ANGPTL3/8 activity.

Apolipoprotein AV (APOA5) lowers plasma triglyceride (TG) levels by binding to the angiopoietin-like protein 3/8 complex (ANGPTL3/8) and suppressing its capacity to inhibit lipoprotein lipase (LPL) catalytic activity and its ability to detach LPL from binding sites within capillaries. However, the sequences in APOA5 that are required for suppressing ANGPTL3/8 activity have never been defined. A clue to the identity of those sequences was the presence of severe hypertriglyceridemia in two patients harboring an APOA5 mutation that truncates APOA5 by 35 residues ("APOA5Δ35"). We found that wild-type (WT) human APOA5, but not APOA5Δ35, suppressed ANGPTL3/8's ability to inhibit LPL catalytic activity. To pursue that finding, we prepared a mutant mouse APOA5 protein lacking 40 C-terminal amino acids ("APOA5Δ40"). Mouse WT-APOA5, but not APOA5Δ40, suppressed ANGPTL3/8's capacity to inhibit LPL catalytic activity and sharply reduced plasma TG levels in mice. WT-APOA5, but not APOA5Δ40, increased intracapillary LPL levels and reduced plasma TG levels in Apoa5-/- mice (where TG levels are high and intravascular LPL levels are low). Also, WT-APOA5, but not APOA5Δ40, blocked the ability of ANGPTL3/8 to detach LPL from cultured cells. Finally, an antibody against a synthetic peptide corresponding to the last 26 amino acids of mouse APOA5 reduced intracapillary LPL levels and increased plasma TG levels in WT mice. We conclude that C-terminal sequences in APOA5 are crucial for suppressing ANGPTL3/8 activity in vitro and for regulating intracapillary LPL levels and plasma TG levels in vivo.

Adsorption of DNA and Aptamers to Sodium Urate Crystals and Inhibition of Crystal Growth.

An elevated level of blood uric acid (UA) can cause the formation of kidney stones, gout, and other diseases. We recently isolated a few DNA aptamers that can selectively bind to UA. In this work, we investigated the adsorption of a UA aptamer and random sequence DNA onto sodium urate crystals. Both DNA strands adsorbed similarly to urate crystals. In addition, both the UA aptamer and random DNA can inhibit the growth of urate crystals, suggesting a nonspecific adsorption mechanism rather than specific aptamer binding. In the presence of 500 nM DNA, the growth of needle-like sodium urate crystals was inhibited, and the crystals appeared granular after 6 h. To understand the mechanism of DNA adsorption, a few chemicals were added to desorb DNA. DNA bases contributed more to the adsorption than the phosphate backbone. Surfactants induced significant DNA desorption. Finally, DNA could also be adsorbed onto real UA kidney stones. This study provides essential insights into the interactions between DNA oligonucleotides and urate crystals, including the inhibition of growth and interface effects of DNA on sodium urate crystals.

Size effect in polymeric lattice materials with size-dependent Poisson's ratio caused by Cosserat elasticity.

Polymeric lattice materials with micro/nano-structures are attractive for applications in a wide range of bioengineering systems. Resent experimental results show that elastic constitutive law of polymer materials is in line with the Cosserat elasticity. In this work, a Cosserat continuum spectral element method is employed to explore the size-dependent mechanical performance of polymer polymeric lattice with horseshoe microstructures, efficiently. The mechanical performance predicted by the proposed method agrees very well with the experiment data. Our results demonstrate that size effects are significant in polymeric lattice materials. The size-dependent negative Poisson's ratio is found in the polymeric lattice materials with the same topological structure due to the size effect caused by the Cosserat elasticity of the polymer materials. It could be implied that it is possible to continuously adjust the negative Poisson's ratio of the polymeric lattice material over a wide range by only changing its microstructural size.

Idiopathic Rapid Eye Movement Sleep Behavior Disorder (iRBD) Shares Similar Fecal Short-Chain Fatty Acid Alterations with Multiple System Atrophy (MSA) and Parkinson's Disease (PD).

BACKGROUND: Idiopathic rapid eye movement sleep behavior disorder (iRBD) is considered as a prodromal stage of synucleinopathies. Fecal short-chain fatty acid (SCFA) changes in iRBD and the relationships with synucleinopathies have never been investigated. OBJECTIVES: To investigate fecal SCFA changes among iRBD, multiple system atrophy (MSA), and Parkinson's disease (PD), and evaluate their relationships. METHODS: Fecal SCFAs and gut microbiota were measured in 29 iRBD, 42 MSA, 40 PD, and 35 normal controls (NC) using gas chromatography-mass spectrometry and 16S rRNA gene sequencing. RESULTS: Compared with NC, fecal SCFA levels (propionic, acetic, and butyric acid) were lower in iRBD, MSA, and PD. Combinations of these SCFAs could differentiate NC from iRBD (AUC 0.809), MSA (AUC 0.794), and PD (AUC 0.701). Decreased fecal SCFAs were associated with the common reducing SCFA-producing gut microbiota in iRBD, MSA, and PD. CONCLUSIONS: iRBD shares similar fecal SCFA alterations with MSA and PD, and the combination of these SCFAs might be a potential synucleinopathies-related biomarker. © 2024 International Parkinson and Movement Disorder Society.

Efficacy of catheter ablation in ganglionated plexus for malignant vasovagal syncope children.

AIM: Malignant vasovagal syncope in children seriously affects their physical and mental health. Our study aimed to explore the efficacy of catheter ablation in ganglionated plexus with malignant vasovagal syncope children. CONCLUSION: Catheter ablation of ganglionated plexus was safe and effective in children with malignant vasovagal syncope and can be used as a treatment option for these children. METHODS: A total of 20 children diagnosed with malignant vasovagal syncope were enrolled in Beijing Children's Hospital, affiliated with Capital Medical University. All underwent catheter ablation treatment of ganglionated plexus. Ganglionated plexuses of the left atrium were identified by high-frequency stimulation and/or anatomic landmarks being targeted by radiofrequency catheter ablation. The efficacy of the treatment was evaluated by comparing the remission rate of post-operative syncopal symptoms and the rate of negative head-up tilt results. Safety and adverse events were evaluated. RESULTS: After follow-up for 2.5 (0.6-5) years, the syncope symptom scores were decreased significantly compared with before treatment [3 (2-4) versus 5 (3-8) scores, P < 0.01]. Eighty-five per cent (17/20) children no longer experienced syncope, whilst 80% (16/20) children showed negative head-up tilt test after treatment. No adverse effects such as cardiac arrhythmia occurred in the children.

Zinc and Chronic Kidney Disease: A Review.

Chronic kidney disease (CKD) poses a major global public health challenge. The World Health Organization's data shows that CKD affects about 10% of the world's population, particularly in low- and middle-income countries. Due to limited access to diagnosis and treatment, CKD has become the 12th leading cause of death worldwide. The advanced stage of CKD can lead to kidney failure, which is clinically referred to as end-stage renal disease (ESRD). In such cases, patients can only sustain life through dialysis or kidney transplantation. However, the long-term affordability of these treatments remains low. Moreover, the effectiveness of kidney transplantation is modest, posing a significant treatment barrier in resource-limited settings, and significantly impacting patient survival. To address this issue, we suggest using dietary supplementation of the trace element zinc to impede CKD development and prolong patient survival.

Dl-3-n-butylphthalide improves stroke outcomes after focal ischemic stroke in mouse model by inhibiting the pyroptosis-regulated cell death and ameliorating neuroinflammation.

Recent studies have highlighted the involvement of pyroptosis-mediated cell death and neuroinflammation in ischemic stroke (IS) pathogenesis. DL-3-n-butylphthalide (NBP), a synthesized compound based on an extract from seeds of Apium graveolens, possesses a broad range of biological effects. However, the efficacy and the underlying mechanisms of NBP in IS remain contentious. Herein, we investigated the therapeutic effects of NBP and elucidated its potential mechanisms in neuronal cell pyroptosis and microglia inflammatory responses. Adult male mice underwent permanent distal middle cerebral artery occlusion (dMCAO), followed by daily oral gavage of NBP (80 mg/kg) for 1, 7, or 21 consecutive days. Gene Expression Omnibus (GEO) dataset of IS patients peripheral blood RNA sequencing was analyzed to identify differentially expressed pyroptosis-related genes (PRGs) during the ischemic process. Our results suggested that NBP treatment effectively alleviated brain ischemic damage, resulting in decreased neurological deficit scores, reduced infarct volume, and improved neurological and behavioral functions. RNA sequence data from human unveiled upregulated PRGs in IS. Subsequently, we observed that NBP downregulated pyroptosis-associated markers at days 7 and 21 post-modeling, at both the protein and mRNA levels. Additionally, NBP suppressed the co-localization of pyroptosis markers with neuronal cells to variable degrees and simultaneously mitigated the accumulation of activated microglia. Overall, our data provide novel evidence that NBP treatment significantly attenuates ischemic brain damage and promotes recovery of neurological function in the early and recovery phases after IS, probably by negatively regulating the pyroptosis cell death of neuronal cells and inhibiting toxic neuroinflammation in the central nervous system.

Effects of water stress on nutrients and enzyme activity in rhizosphere soils of greenhouse grape.

In grape cultivation, incorrect water regulation will lead to significant water wastage, which in turn will change soil structure and disrupt soil nutrient cycling processes. This study aimed to investigate the effects of different water regulation treatments [by setting moderate water stress (W1), mild water stress (W2), and adequate water availability (CK)] on soil physical-chemical properties and enzyme activity in greenhouse grape during the growing season. The result showed that the W2 treatment had a negative impact on the build-up of dissolved organic carbon (DOC), nitrate nitrogen (NO3-N), and available phosphorus (AP). Throughout the reproductive period, the W1 and W2 treatments decreased the soil's microbial biomass carbon (MBC) and microbial biomass nitrogen (MBN) contents, and MBC was more vulnerable to water stress. During the growth period, the trends of urease, catalase, and sucrase activities in different soil depth were ranked as 10-20 cm > 0-10 cm > 20-40 cm. The urease activity in 0-10 cm soil was suppressed by both W1 and W2 treatments, while the invertase activity in various soil layers under W1 treatment differed substantially. The W1 treatment also reduced the catalase activity in the 20-40 cm soil layer in the grape growth season. These findings suggested that W2 treatment can conserve water and enhance microbial ecology of greenhouse grape soils. Therefore, W2 treatment was the most effective water regulation measure for local greenhouse grape cultivation.

Enhancing Electrochemical Signal for Efficient Chiral Recognition by Encapsulating C60 Fullerene into Chiral Lanthanum-Based MOFs.

Chiral metal-organic frameworks (MOFs) have attracted much attention due to their highly tunable regular microporous structures. However, chiral electrochemical recognition based on chiral MOFs is often limited by poor charge separation and slow charge transfer kinetics. In this case, C60 can be encapsulated into the cavity of [La(BTB)]n by virtue of host-guest interactions through π-π stacking to synthesize the chiral composite C60@[La(BTB)]n and amplify electrochemically controlled enantioselective interactions with the target enantiomers. A large electrostatic potential difference is generated in chiral C60@[La(BTB)]n due to the host-guest interaction and the inhomogeneity of the charge distribution, leading to the generation of a strong built-in electric field and thus an overall enhancement of the conductivity of the chiral material. Their enantioselective detection of tryptophan enantiomers was demonstrated by electrochemical measurement. The results showed that chiral MOF materials can be used for enantiomeric recognition. It is worth noting that this new material derived from the concept of host-guest interaction to enhance charge separation opens up unprecedented possibilities for future enantioselective recognition and separation.

[High performance liquid chromatography combined with the 2,2'-dithiodipyridine derivatization reaction for determination of different types of free thiols in human serum and analysis of their relationship with coronary heart disease].

Oxidative stress, which is characterized by an imbalance between antioxidants and free radicals, plays a pivotal role in the pathogenesis of coronary heart disease, a common and serious cardiovascular condition, and contributes significantly to its development and progression. Serum free thiols are crucial components of the body's antioxidant defense system. The accurate determination of serum free thiol levels provides a reference basis for understanding the body's status and monitoring the risk factors associated with the occurrence and progression of coronary heart disease. In this study, a high performance liquid chromatographic (HPLC) method based on the derivatization reaction of 2,2'-dithiodipyridine was developed to simultaneously obtain the concentrations of total free thiols (Total-SH), low-molecular-mass free thiols (LMM-SH), and protein-free thiols (P-SH) in human serum. An Agilent Eclipse XDB-C18 column (150 mm×4.6 mm, 5 µm) was used for the analysis, and gradient elution was performed at a flow rate of 1 mL/min. A 0.1% formic acid aqueous solution was used as mobile phase A, and a 0.1% formic acid acetonitrile solution was used as mobile phase B. The gradient elution program was as follows: 0-0.1 min, 12%B-30%B; 0.1-2 min, 30%B; 2-2.1 min, 30%B-100%B; 2.1-6 min, 100%B; 6-6.1 min, 100%B-12%B; 6.1-7 min, 12%B. Well-separated peaks appeared after a run time of 5 min. The peak of 2-thiopyridone represented the Total-SH content of the samples, and the peak of the pyridyldithio derivative represented the LMM-SH content. The difference between these two peaks indicated the P-SH content. The derivatization reaction conditions were optimized, and the method was validated. The method demonstrated good linearity, with a correlation coefficient ≥0.9994, over the concentration range of 31.25-1000 µmol/L. The limits of detection for Total-SH and LMM-SH were 2.61 and 0.50 µmol/L, and the limits of quantification for Total-SH and LMM-SH were 8.71 and 1.67 µmol/L, respectively. The recoveries of Total-SH and LMM-SH were in the range of 91.1%-106.0%. The intra- and inter-day precisions ranged from 0.4% to 9.1%. The developed method was used to analyze serum samples from 714 volunteers. The Total-SH concentrations ranged from 376.60 to 781.12 µmol/L, with an average concentration of 555.62 µmol/L. The LMM-SH concentrations varied from 36.37 to 231.65 µmol/L,with an average of 82.34 µmol/L. The P-SH concentrations ranged from 288.36 to 687.74 µmol/L, with an average of 473.27 µmol/L. Spearman's correlation test showed that serum thiol levels were correlated with the severity of coronary artery disease and common clinical biochemical indicators. The proposed study provides a simple and reliable HPLC method for detecting serum free thiols and exploring their relationship with coronary heart disease, offering a new reference for the study of markers related to the risk of coronary heart disease.

High LGALS3 expression induced by HCP5/hsa-miR-27b-3p correlates with poor prognosis and tumor immune infiltration in hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is widely recognized for its unfavorable prognosis. Increasing evidence has revealed that LGALS3 has an essential function in initiating and developing several malignancies in humans. Nevertheless, thorough analysis of the expression profile, clinical prognosis, pathway prediction, and immune infiltration of LGALS3 has not been fully explored in HCC. METHODS: In this study, an initial pan-cancer analysis was conducted to investigate the expression and prognosis of LGALS3. Following a comprehensive analysis, which included expression analysis and correlation analysis, noncoding RNAs that contribute to the overexpression of LGALS3 were subsequently identified. This identification was further validated using HCC clinical tissue samples. TIMER2 and GEPIA2 were employed to examine the correlation between LGALS3 and HCP5 with immunological checkpoints, cell chemotaxis, and immune infiltration in HCC. The R program was applied to analyze the expression distribution of immune score in in HCC patients with high and low LGALS3 expression. The expression profiles of immune checkpoints were also analyzed. Use R to perform GSVA analysis in order to explore potential signaling pathways. RESULTS: First, we conducted pan-cancer analysis for LGALS3 expression level through an in-depth analysis of public databases and found that HCC has a high LGALS3 gene and protein expression level, which were then verified in clinical HCC specimens. Meanwhile, high LGALS3 gene expression is related to malignant progression and poor prognosis of HCC. Univariate and multivariate analyses confirmed that LGALS3 could serve as an independent prognostic marker for HCC. Next, by combining comprehensive analysis and validation on HCC clinical tissue samples, we hypothesize that the HCP5/hsa-miR-27b-3p axis could serve as the most promising LGALS3 regulation mechanism in HCC. KEGG and GO analyses highlighted that the LGALS3-related genes were involved in tumor immunity. Furthermore, we detected a significant positive association between LGALS3 and HCP5 with immunological checkpoints, cell chemotaxis, and immune infiltration. In addition, high LGALS3 expression groups had significantly higher immune cell scores and immune checkpoint expression levels. Finally, GSVA analysis was performed to predict potential signaling pathways linked to LGALS3 and HCP5 in immune evasion and metabolic reprogramming of HCC. CONCLUSIONS: Our findings indicated that the upregulation of LGALS3 via the HCP5/hsa-miR-27b-3p axis is associated with unfavorable prognosis and increased tumor immune infiltration in HCC.

Hepatitis C virus subtype diversity and transmission clusters characteristics among drug users in Zhuhai, South China.

BACKGROUND: Hepatitis C virus (HCV) infection poses a major public health challenge globally, especially among injecting drug users. China has the world's largest burden of HCV infections. However, little is known about the characteristics of transmission networks among drug user populations. This study aims to investigate the molecular epidemiology and transmission characteristics of HCV infections among drug users in Zhuhai, a bustling port city connecting Mainland China and its Special Administrative Regions. METHODS: Participants enrolled in this study were drug users incarcerated at Zhuhai's drug rehabilitation center in 2015. Their sociodemographic and behavioral information, including gender, promiscuity, drug use method, and so forth, was collected using a standardized questionnaire. Plasmas separated from venous blood were analyzed for HCV infection through ELISA and RT-PCR methods to detect anti-HCV antibodies and HCV RNA. The 5'UTR fragment of the HCV genome was amplified and further sequenced for subtype identifications and phylogenetic analysis. The phylogenetic tree was inferred using the Maximum Likelihood method based on the Tamura-Nei model, and the transmission cluster network was constructed using Cytoscape3.8.0 software with a threshold of 0.015. Binary logistic regression models were employed to assess the factors associated with HCV infection. RESULTS: The overall prevalence of HCV infection among drug users was 44.37%, with approximately 19.69% appearing to clear the HCV virus successfully. Binary logistic regression analysis revealed that those aged over 40, engaging in injecting drug use, and being native residents were at heightened risk for HCV infection among drug user cohorts. The predominant HCV subtypes circulating among those drug users were 6a (60.26%), followed by 3b (16.7%), 3a (12.8%), 1b (6.41%) and 1a (3.85%), respectively. Molecular transmission network analysis unveiled the presence of six transmission clusters, with the largest propagation cluster consisting of 41 individuals infected with HCV subtype 6a. Furthermore, distinct transmission clusters involved eight individuals infected with subtype 3b and seven with subtype 3a were also observed. CONCLUSION: The genetic transmission networks revealed a complex transmission pattern among drug users in Zhuhai, emphasizing the imperative for a targeted and effective intervention strategy to mitigate HCV dissemination. These insights are pivotal for shaping future national policies on HCV screening, treatment, and prevention in port cities.

Exosomes based strategies for cardiovascular diseases: Opportunities and challenges.

Exosomes, as nanoscale extracellular vesicles (EVs), are secreted by all types of cells to facilitate intercellular communication in living organisms. After being taken up by neighboring or distant cells, exosomes can alter the expression levels of target genes in recipient cells and thereby affect their pathophysiological outcomes depending on payloads encapsulated therein. The functions and mechanisms of exosomes in cardiovascular diseases have attracted much attention in recent years and are thought to have cardioprotective and regenerative potential. This review summarizes the biogenesis and molecular contents of exosomes and details the roles played by exosomes released from various cells in the progression and recovery of cardiovascular disease. The review also discusses the current status of traditional exosomes in cardiovascular tissue engineering and regenerative medicine, pointing out several limitations in their application. It emphasizes that some of the existing emerging industrial or bioengineering technologies are promising to compensate for these shortcomings, and the combined application of exosomes and biomaterials provides an opportunity for mutual enhancement of their performance. The integration of exosome-based cell-free diagnostic and therapeutic options will contribute to the further development of cardiovascular regenerative medicine.

Improvements in Neoplasm Classification in the International Classification of Diseases, Eleventh Revision: Systematic Comparative Study With the Chinese Clinical Modification of the International Classification of Diseases, Tenth Revision.

BACKGROUND: The International Classification of Diseases, Eleventh Revision (ICD-11) improved neoplasm classification. OBJECTIVE: We aimed to study the alterations in the ICD-11 compared to the Chinese Clinical Modification of the International Classification of Diseases, Tenth Revision (ICD-10-CCM) for neoplasm classification and to provide evidence supporting the transition to the ICD-11. METHODS: We downloaded public data files from the World Health Organization and the National Health Commission of the People's Republic of China. The ICD-10-CCM neoplasm codes were manually recoded with the ICD-11 coding tool, and an ICD-10-CCM/ICD-11 mapping table was generated. The existing files and the ICD-10-CCM/ICD-11 mapping table were used to compare the coding, classification, and expression features of neoplasms between the ICD-10-CCM and ICD-11. RESULTS: The ICD-11 coding structure for neoplasms has dramatically changed. It provides advantages in coding granularity, coding capacity, and expression flexibility. In total, 27.4% (207/755) of ICD-10 codes and 38% (1359/3576) of ICD-10-CCM codes underwent grouping changes, which was a significantly different change (χ21=30.3; P<.001). Notably, 67.8% (2424/3576) of ICD-10-CCM codes could be fully represented by ICD-11 codes. Another 7% (252/3576) could be fully described by uniform resource identifiers. The ICD-11 had a significant difference in expression ability among the 4 ICD-10-CCM groups (χ23=93.7; P<.001), as well as a considerable difference between the changed and unchanged groups (χ21=74.7; P<.001). Expression ability negatively correlated with grouping changes (r=-.144; P<.001). In the ICD-10-CCM/ICD-11 mapping table, 60.5% (2164/3576) of codes were postcoordinated. The top 3 postcoordinated results were specific anatomy (1907/3576, 53.3%), histopathology (201/3576, 5.6%), and alternative severity 2 (70/3576, 2%). The expression ability of postcoordination was not fully reflected. CONCLUSIONS: The ICD-11 includes many improvements in neoplasm classification, especially the new coding system, improved expression ability, and good semantic interoperability. The transition to the ICD-11 will inevitably bring challenges for clinicians, coders, policy makers and IT technicians, and many preparations will be necessary.

HCC portal hypertension imaging score derived from CT predicts re-bleeding and mortality after acute variceal bleeding.

BACKGROUND/PURPOSE: Risk factors for re-bleeding and death after acute variceal bleeding (AVB) in cirrhotic HCC patients are not fully understood.We aimed to (1) explore how the combination of high-risk esophageal varices, HCC status, and portal vein tumor thrombus (i.e., HCC Portal Hypertension Imaging Score [HCCPHTIS]) helps predict increased risk of variceal re-bleeding and mortality; (2) assess predictability and reproducibility of the identified variceal re-bleeding rules. METHODS: This prospective study included 195 HCC patients with first-time AVB and liver cirrhosis, and conducted multivariable Cox regression analysis and Kaplan-Meier analysis. Receiver operating characteristic curve analysis was calculated to find the optimal sensitivity, specificity, and cutoff values of the variables. The reproducibility of the results obtained was verified in a different but related group of patients. RESULTS: 56 patients (28.7%) had re-bleeding within 6 weeks; HCCPHTIS was an independent risk factor for variceal re-bleeding after AVB (Odd ratio, 2.330; 95% confidence interval: 1.728-3.142, p < 0.001). The positive predictive value of HCCPHTIS cut off value > 3 was 66.2%, sensitivity 83.9%, and specificity 82.3%. HCCPHTIS area under the curve was higher than Child-Pugh score (89% vs. 75%, p < 0.001). 74(37.9%) death occurred within 6 weeks; HCCPHTIS > 4 was associated with increased risk of death within 6 weeks after AVB (p < 0.001). CONCLUSION: HCCPHTIS > 3 is a strong predictor of variceal re-bleeding within the first 6 weeks. However, patients with HCCPHTIS > 4 were at increased risk of death within 6 weeks.