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Tyramine signaling amplification (TSA) technology is generally applied in immunofluorescence, enzyme-linked immunoassays, in situ hybridization techniques, etc. Successful amplification of fluoresence signals cannot be achieved without excellent fluorescent dyes. BODIPY fluorophore is an ideal probe for cell fluorescence imaging, but pristine BODIPY cannot be direct used in the TSA system. In the paper, the new red-shifted tyramide-conjugated BODIPY (BDP-B/C/D) was synthesized via the Knoevenagel condensation reaction, which based on the tyramide-conjugated BODIPY (BDP-A). The synthesized dyes were combined with tyramine to obtain which could be used as a fluorescent substrate for enzymatic reaction of TSA. By using the selected substrate (BDP-C) in TSA, we found it to be more sensitive than the commercial dye 594 styramide for the detection of low-abundance antigen proteins.

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Background: Clearance of human papillomavirus (HPV) among adolescent men who have sex with men (MSM) is not well studied. This study aimed to evaluate the clearance of HPV DNA and antibodies among adolescent MSM. Methods: In our cohort study, we enrolled adolescent MSM in Melbourne between October 2010 and September 2013. At baseline, 3, 6, and 12 months, anal and penile swabs for HPV DNA and serum for HPV antibodies against genotypes 6, 11, 16, and 18, were collected. Definite clearance was defined as HPV DNA (same site) /antibodies for the same genotype undetected following a positive HPV DNA /antibodies test at baseline or month 3. Possible clearance was defined as HPV DNA (same site) /antibodies for the same genotype undetected at month 12 following a positive HPV DNA/antibodies test at month 6. Overall clearance was defined as either definite or possible clearance. The agreement between HPV DNA clearance and antibodies clearance was calculated. Results: A total of 183 MSM were included (median age: 19 years, interquartile [IQR]: 18 to 20). At the anus, overall clearance rate was 21.6 (95 % confidence interval[CI]: 7.9 to 47.0), 44.8 (19.3 to 88.3), 51.9 (20.9 to 106.9) and 33.7 (7.0 to 98.5) per 1000 person months (PM) for HPV 6, 11, 16 and 18. At the penis, overall clearance rate was 64.5 (13.3 to 188.5), 71.3 (14.7 to 208.2), 96.5 (31.3 to 225.3) and 333.3 (8.4 to 1857.2) per 1000 PM for HPV 6, 11, 16 and 18. For antibodies, overall clearance rate was 22.2 (9.6 to 43.7), 18.8 (3.9 to 55.0), 10.8 (0.3 to 60.1) and 19.0 (2.3 to 68.8) per 1000 PM. Agreement between anal/penile HPV DNA clearance and antibodies clearance was low: kappa = -0.18 (95 % CI: -0.28 to 0.08)/-0.13 (-0.24 to -0.02), 0.04 (-0.29 to 0.36)/0.22 (-0.32 to 0.76), -0.10 (-0.27 to 0.08)/-0.14 (-0.37 to 0.10) and -0.14 (-0.28 to 0.01)/-0.14 (-0.33 to 0.06) for HPV 6, 11, 16 and 18, respectively. Conclusion: Clearance rates of HPV DNA were low and varied by genotypes and anatomical sites among adolescent MSM. Antibodies against HPV were stable during the study period.

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BACKGROUND AND OBJECTIVE: To explore the association between protein quantitative trait loci (pQTL-SNPs) and the risk of LUAD. METHODS: "Blood +" high depth blood proteomics analysis was performed on plasma from female LUAD patients and female healthy controls, and combined with proteomics data from tumors and adjacent non-tumor tissues of female LUAD patients to screen proteins uniformly expressed in plasma and tissues. pQTL-SNPs were then screened through multiple databases and subjected to multilevel screening. The associations between selected pQTL-SNPs and LUAD risk were evaluated by Female Lung Cancer Consortium in Asia GWAS (FLCCA GWAS). Enzyme linked immunosorbent assay (ELISA) is used to determine the levels of candidate protein. RESULTS: A total of 7 pQTL-SNPs were significantly associated with altered LUAD risk (p < 0.05). Meanwhile, the expression of their corresponding target proteins were all decreased in both plasma and tumor tissues of LUAD cases, which may play a role of tumor suppressor proteins. After mutation of 3 pQTL-SNPs (rs7683000, rs73224660, and rs2776937), the expression of corresponding target proteins BST1 and NRP1 decreased, and as potential tumor suppressor proteins, which may promote tumorigenesis and further increasing the risk of developing LUAD (OR >1, p < 0.05); while after mutation the other pQTL-SNP rs62069916, the corresponding target protein APOH expression was increased, while as a potential tumor suppressor protein, which may inhibit tumorigenesis and further reduced the risk of developing LUAD (OR <1, p < 0.05). In addition, the expression of NRP1 and APOH were significant decreased in LUAD cell lines and validated in plasma of LUAD patients. CONCLUSION: A total of 4 pQTL-SNPs (rs7683000, rs73224660, rs2776937, and rs62069916) may associate with altered LUAD risk by regulating the expression of target proteins (BST1, NRP1, and APOH) after mutation.

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An efficient electrochemiluminescence (ECL) emitter, Ir(ppy)3-based molecules has recently been reported to exhibit aggregation-induced electrochemiluminescence (AIECL) phenomenon. However, it remains a significant challenge to control the aggregation states of these molecules and achieve uniform aggregates with intense ECL emission. In this work, a biosensor was developed to detect microcystin-LR (MC-LR) based on Ir(ppy)3-functionalized zeolitic imidazolate framework-8 (Ir-ZIF-8) as the ECL emitter and the trans-cleavage activity of CRISPR-Cas12a as the methodological strategy. The Ir-ZIF-8, a functional metal-organic framework (MOF), exhibited the AIECL phenomenon via the spatial domain-limiting effect of encapsulating Ir(ppy)3 into the mesopores of ZIF-8, while the porosity and highly ordered topological structure of ZIF-8 effectively limited the molecular motion of Ir(ppy)3. CRISPR-Cas12a was employed to indiscriminately cleave double-stranded DNA decorated with carboxy tetramethylrhodamine (TAMRA), which quenched the ECL signal of Ir-ZIF-8 by resonance energy transfer and then separated the quencher from Ir-ZIF-8 to reactivate the signal. The concentration of MC-LR was designed to correlate with both the quencher amount and the activity of Cas12a. Then, two linear regression equations for MC-LR detection were constructed to improve the accuracy of the biosensor, and the constructed biosensor showed remarkable reproducibility, stability, and selectivity. The accurate detection of MC-LR with limits of detection of 1.2 and 5.9 pg/mL was made possible by the high quenching efficiency of TAMRA and the effective cutting ability of the editable CRISPR-Cas12a system.

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Background: The demand for fertility-sparing surgery (FSS) is increasing among patients with early-stage cervical cancer (CC). This study aimed to evaluate the feasibility of local excision as an alternative to hysterectomy in stage I CC patients aged 15-39 years-commonly referred to as adolescents and young adults (AYAs)-with varying clinicopathological characteristics. Methods: Using the Surveillance, Epidemiology, and End Results (SEER) database, we identified patients diagnosed between 2000 and 2020. We examined treatment interventions across different age groups, degrees of histological types, tumor differentiation, and tumor stages. The effect of local excision vs. hysterectomy was assessed by comparing overall survival (OS) and disease-specific survival (DSS) rates. Results: A total of 10,629 stage I AYA cervical cancer patients were included in this study. Among these patients, 24.5% underwent local excision for fertility preservation, while 67.3% underwent radical hysterectomy. For patients with cervical squamous cell carcinoma (SCC), long-term outcomes favored local excision over hysterectomy, and a similar trend was observed in those with adenosquamous cell carcinoma (ASCC). However, the prognosis was comparable among patients with cervical adenocarcinoma (AC). In patients with well- and moderate- differentiated tumors, local excision demonstrated superior OS compared to hysterectomy. No significant differences in prognosis were found between the two surgical interventions for patients with poorly differentiated and undifferentiated tumors. In stage IA patients, local excision was considered a viable alternative to hysterectomy. In stage IB1-IB2, FSS yielded prognostic outcomes comparable to those of hysterectomy. Conversely, patients with stage IB3 exhibited significantly shorter 5-year OS and DSS following local excision than those who underwent hysterectomy. Conclusion: In stage IA-IB2 (diameter ≤4 cm) AYA patients, local excision may serve as a viable option for fertility preservation. The histological type of SCC, AC, and ASCC, along with differentiation, should not serve as restrictive factors in determining fertility preservation strategies for these patients. Patients with early-stage, well- or moderately-differentiated SCC may benefit from local excision surgery, even when fertility preservation is not the primary objective.

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Persistent truncus arteriosus (PTA) is a rare congenital heart malformation. A 4-year-old girl was diagnosed with type I PTA through echocardiography and confirmed by cardiac CTA.

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BACKGROUND: Sleep and physical activity (PA) are thought to be interconnected with the development of rheumatoid arthritis (RA). However, the precise nature and extent of these relationships have yet to be fully quantified. This study aimed to quantify the longitudinal effects of sleep behaviors, PA, and genetic susceptibility on the incidence of RA and to estimate the combined effects and interactions among these exposures. METHODS: A total of 363,211 adults were derived from a large European cohort. We incorporated five sleep behaviors (sleep duration, insomnia, snoring, chronotype, and daytime sleepiness) to generate sleep patterns, which were defined based on healthy sleep scores. Multivariate-adjusted Cox proportional hazard models were conducted to assess the individual and combined associations of sleep patterns, PA, and genetic susceptibility with the risk of RA occurrence. Multiplicative and additive interactions were estimated by Pinteraction and relative excess risk due to interaction (RERI) between each of the two exposures. RESULTS: During a follow-up of 12.5 years, 4262 RA cases were ascertained. A healthy sleep pattern was associated with a decreased risk of RA in a dose-response manner, with an adjusted hazard ratio (HR) of 0.79 (95% confidence interval [CI] = 0.75-0.84), independent of traditional risk factors and genetic predisposition. Under the restricted cubic splines model, a non-linear association was detected for PA and RA risk. Participants in the intermediate quintile 3 showed the lowest risk for developing RA, with a HR 95% CI of 0.84 (0.76-0.92). Moreover, there was an additive interaction effect of intermediate sleep pattern and PA, with a 0.45 (95% CI = 0.02-0.87) RERI of developing RA. Additionally, individuals at high genetic risk had the greatest 10-year absolute risk reduction (10.58 per 1000 person-years) when adopting both favorable behaviors. CONCLUSIONS: A healthy sleep pattern and moderate PA were associated with a reduced risk of developing RA, which can offset the deleterious effects of predisposing genetic components. Implementing these modifiable lifestyle factors into public health practices is beneficial for RA prevention.

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BACKGROUND: With the backdrop of global climate change, the impact of climate change on respiratory diseases like asthma is receiving increasing attention. However, the effects of temperature and diurnal temperature range (DTR) on asthma are complex, and understanding these effects across different seasons, age groups, and sex is of utmost importance. METHODS: This study utilized asthma hospitalization data from Lanzhou, China, and implemented a distributed lag nonlinear model (DLNM) to investigate the relationship between temperature and DTR and asthma hospitalizations. It considered differences in the effects across various seasons and population subgroups. RESULTS: The study revealed that low temperatures immediately increase the risk of asthma hospitalization (RR = 1.2010, 95% CI: 1.1464, 1.2580), and this risk persists for a period of time. Meanwhile, both high and low DTR were associated with an increased risk of asthma hospitalization. Lower temperatures (RR = 2.9798, 95% CI: 1.1154, 7.9606) were associated with higher asthma risk in the warm season, while in the cold season, the risk significantly rose for the general population (RR = 3.6867, 95% CI: 1.7494, 7.7696), females (RR = 7.2417, 95% CI: 2.7171, 19.3003), and older individuals (RR = 18.5425, 95% CI: 5.1436, 66.8458). In the warm season, low DTR conditions exhibited a significant association with asthma hospitalization risk in males (RR = 7.2547, 95% CI: 1.2612, 41.7295) and adults aged 15-64 (RR = 9.9494, 95% CI: 2.2723, 43.5643). Children also exhibited noticeable risk within specific DTR ranges. In the cold season, lower DTR increases the risk of asthma hospitalization for the general population (RR = 3.1257, 95% CI: 1.4004, 6.9767). High DTR significantly increases the risk of asthma hospitalization in adults (RR = 5.2563, 95% CI: 2.4131, 11.4498). CONCLUSION: This study provides crucial insights into the complex relationship between temperature, DTR, and asthma hospitalization, highlighting the variations in asthma risk across different seasons and population subgroups.

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Abnormal activation of the YAP transcriptional signaling pathway drives proliferation in many hepatocellular carcinoma (HCC) and hepatoblastoma (HB) cases. Current treatment options often face resistance and toxicity, highlighting the need for alternative therapies. This article reports the discovery of a hit compound C-3 from docking-based virtual screening targeting TEAD lipid binding pocket, which inhibited TEAD-mediated transcription. Optimization led to the identification of a potent and covalent inhibitor CV-4-26 that exhibited great antitumor activity in HCC and HB cell lines in vitro, xenografted human HCC, and murine HB in vivo. These outcomes signify the potential of a highly promising therapeutic candidate for addressing a subset of HCC and HB cancers. In the cases of current treatment challenges due to high upregulation of YAP-TEAD activity, these findings offer a targeted alternative for more effective interventions against liver cancer.

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Interferon regulatory factor-8 (IRF8) is the lineage determining transcription factor for the type one classical dendritic cell (cDC1) subset, a terminal selector for plasmacytoid dendritic cells and important for the function of monocytes. Studies of Irf8 gene regulation have identified several enhancers controlling its activity during development of progenitors in the bone marrow that precisely regulate expression at distinct developmental stages. Each enhancer responds to distinct transcription factors that are expressed at each stage. IRF8 is first expressed in early progenitors that form the monocyte dendritic cell progenitor (MDP) in response to induction of the transcription factor CCAAT/enhancer-binding protein alpha (C/EBPα) acting at the Irf8 +56 kb enhancer. IRF8 levels increase further as the MDP transits into the common dendritic cell progenitor (CDP) in response to E protein activity at the Irf8 +41 kb enhancer. Upon Nfil3-induction in CDPs leading to specification of the cDC1 progenitor, abrupt induction of BATF3 forms the JUN/BATF3/IRF8 heterotrimer that activates the Irf8 +32 kb enhancer that sustains Irf8 autoactivation throughout the cDC1 lifetime. Deletions of each of these enhancers has revealed their stage dependent activation. Surprisingly, studies of compound heterozygotes for each combination of enhancer deletions revealed that activation of each subsequent enhancer requires the successful activation of the previous enhancer in strictly cis-dependent mechanism. Successful progression of enhancer activation is finely tuned to alter the functional accessibility of subsequent enhancers to factors active in the next stage of development. The molecular basis for these phenomenon is still obscure but could have implications for genomic regulation in a broader developmental context.

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Expanding target pesticide species and intelligent pesticide recognition were formidable challenges for existing cholinesterase inhibition methods. To improve this status, multi-active Mel-Cu nanozyme with mimetic Cu-N sites was prepared for the first time. It exhibited excellent laccase-like and peroxidase-like activities, and can respond to some pesticides beyond the detected range of enzyme inhibition methods, such as glyphosate, carbendazim, fumonisulfuron, etc., through coordination and hydrogen bonding. Inspired by the signal complementarity of Mel-Cu and cholinesterase, an integrated sensor array based on the Mel-Cu laccase-like activity, Mel-Cu peroxidase-like activity, acetylcholinesterase, and butyrylcholinesterase was creatively constructed. And it could successfully discriminate 12 pesticides at 0.5-50 µg/mL, which was significantly superior to traditional enzyme inhibition methods. Moreover, on the basis of above array, a unified stepwise prediction model was built using classification and regression algorithms in machine learning, which enabled concentration-independent qualitative identification as well as precise quantitative determination of multiple pesticide targets, simultaneously. The sensing accuracy was verified by blind sample analysis, in which the species was correctly identified and the concentration was predicted within 10% error, suggesting great intelligent recognition ability. Further, the proposed method also demonstrated significant immunity to interference and practical application feasibility, providing powerful means for pesticide residue analysis.

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BACKGROUND: Currently, there are no optimal biomarkers available for distinguishing patients who will respond to immune checkpoint inhibitors (ICIs) therapies. Consequently, the exploration of novel biomarkers that can predict responsiveness to ICIs is crucial in the field of immunotherapy. METHODS: We estimated the proportions of 22 immune cell components in 10 cancer types (6,128 tumors) using the CIBERSORT algorithm, and further classified patients based on their tumor immune cell proportions in a pan-cancer setting using k-means clustering. Differentially expressed immune genes between the patient subgroups were identified, and potential predictive biomarkers for ICIs were explored. Finally, the predictive value of the identified biomarkers was verified in patients with urothelial carcinoma (UC) and esophageal squamous cell carcinoma (ESCC) who received ICIs. RESULTS: Our study identified two subgroups of patients with distinct immune infiltrating phenotypes and differing clinical outcomes. The patient subgroup with improved outcomes displayed tumors enriched with genes related to immune response regulation and pathway activation. Furthermore, CCL5 and CSF2 were identified as immune-related hub-genes and were found to be prognostic in a pan-cancer setting. Importantly, UC and ESCC patients with high expression of CCL5 and low expression of CSF2 responded better to ICIs. CONCLUSION: We demonstrated CCL5 and CSF2 as potential novel biomarkers for predicting the response to ICIs in patients with UC and ESCC. The predictive value of these biomarkers in other cancer types warrants further evaluation in future studies.

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SMAD4 deficiency in colorectal cancer (CRC) is highly correlated with liver metastasis and high mortality, yet there are few effective precision therapies available. Here, we show that CCR1+-granulocytic myeloid-derived suppressor cells (G-MDSCs) are highly infiltrated in SMAD4-deficient CRC via CCL15/CCR1 and CCL9/CCR1 axis in clinical specimens and mouse models, respectively. The excessive TGF-ß, secreted by tumor-infiltrated CCR1+-G-MDSCs, suppresses the immune response of cytotoxic T lymphocytes (CTLs), thus facilitating metastasis. Hereby, we develop engineered nanovesicles displaying CCR1 and TGFBR2 molecules (C/T-NVs) to chemotactically target the tumor driven by CCL9/CCR1 axis and trap TGF-ß through TGF-ß-TGFBR2 specific binding. Chemotactic C/T-NVs counteract CCR1+-G-MDSC infiltration through competitive responding CCL9/CCR1 axis. C/T-NVs-induced intratumoral TGF-ß exhaustion alleviates the TGF-ß-suppressed immune response of CTLs. Collectively, C/T-NVs attenuate liver metastasis of SMAD4-deficient CRC. In further exploration, high expression of programmed cell death ligand-1 (PD-L1) is observed in clinical specimens of SMAD4-deficient CRC. Combining C/T-NVs with anti-PD-L1 antibody (aPD-L1) induces tertiary lymphoid structure formation with sustained activation of CTLs, CXCL13+-CD4+ T, CXCR5+-CD20+ B cells, and enhanced secretion of cytotoxic cytokine interleukin-21 and IFN-γ around tumors, thus eradicating metastatic foci. Our strategy elicits pleiotropic antimetastatic immunity, paving the way for nanovesicle-mediated precision immunotherapy in SMAD4-deficient CRC.

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This research presents a unique small molecule characterized by its ability to effectively disrupt RNA G-quadruplexes (G4s), which are notably more stable than their DNA counterparts. We conducted a comprehensive series of in vitro experiments to thoroughly assess the disruptive capabilities of this molecule on RNA G4s. These experiments included comparisons with established G4 stabilizers and DNA G4 disruptors, providing a multifaceted evaluation of the molecule's efficacy. Our extensive in vitro analyses demonstrated that this molecule effectively alters G4 structures and interactions with the BG4 protein, a well-recognized G4-specific antibody. These findings underscore the molecule's potential to modulate G4-protein interactions, indicating promising applications for manipulating cellular functions associated with G4 dynamics in future research.

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Previous studies showed that serum amyloid A (SAA) and macrophages were associated with allergic airway inflammation. However, the interaction between SAA1 and macrophages in allergic airway inflammation remains to be further elucidated. In this study, the levels of SAA1 were measured in nasal tissues from patients with eosinophilic chronic rhinosinusitis with nasal polyps (CRSwNP), house dust mite (HDM)-treated BEAS-2B cells and the tissues of mice of HDM-induced allergic airway inflammation. Human monocytes-derived macrophages and mouse bone marrow-derived macrophages (BMDMs) were exposed to SAA1, and CCL17 and the other M1/M2-related factors were evaluated using RT-PCR and/or ELISA. To test the effects of SAA1-treated BMDMs on chemotaxis and differentiation of CD4+ T cells, number of migrated cells and the levels of Th1 and Th2 were measured using flow cytometry. SAA1 receptors were examined in BMDMs and lung macrophages of model mice. CD36 neutralizing antibody was applied to explore the mechanisms of SAA1 in regulating BMDMs using RT-PCR and/or ELISA. We found that SAA1 was expressed in epithelial cells, and was increased in the nasal tissues of patients with eosinophilic CRSwNP and HDM-treated BEAS-2B- cells as well as the bronchoalveolar lavage fluid and lung tissues of mice exposed to HDM. We also found that the level of CCL17 was increased in M2 macrophages, more CD4+ T cells were recruited and proportion of Th2 was increased after the treatment of SAA1. The treatment of CD36 neutralizing antibody decreased CCL17 level in SAA1-treated M2 BMDMs. In summary, our results showed that SAA1 was increased in allergic airway inflammation, and the administration of SAA1 upregulated the expression of CCL17 in M2 macrophages via CD36 and promoted the chemotaxis of CD4+ T cells and differentiation of Th2. It may provide a new therapeutic strategy that could mediate allergic airway inflammation via suppressing SAA1 to reduce recruitment of CD4+ T cells and activation of Th2.

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Germinal matrix-intraventricular hemorrhage (GM-IVH) is a detrimental neurological complication that occurs in preterm infants, especially in babies born before 32 weeks of gestation and in those with a very low birth weight. GM-IVH is defined as a rupture of the immature and fragile capillaries located in the subependymal germinal matrix zone of the preterm infant brain, and it can lead to detrimental neurological sequelae such as posthemorrhagic hydrocephalus (PHH), cerebral palsy, and other cognitive impairments. PHH following GM-IVH is difficult to treat in the clinic, and no levelone strategies have been recommended to pediatric neurosurgeons. Several cellular and molecular mechanisms of PHH following GM-IVH have been studied in animal models, but no effective pharmacological strategies have been used in the clinic. Thus, a comprehensive understanding of molecular mechanisms, potential pharmacological strategies, and surgical management of PHH is urgently needed. The present review presents a synopsis of the pathogenesis, diagnosis, and cellular and molecular mechanisms of PHH following GM-IVH and explores pharmacological strategies and surgical management.

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Gardenia jasminoides Ellis. polysaccharide (GPS) can protect against cholestatic liver injury (CLI) by regulating nuclear farnesoid X receptor (FXR).However, the mechanism via which GPS mediates the FXR pathway remains unclear. The aim of this study was to investigate the mechanism. Firstly, an alpha-naphthylisothiocyanate-induced cholestatic mouse model was administered with GPS to evaluate its hepatoprotective effects. The metabolic pathways influenced by GPS in cholestatic mice were detected by serum metabolomics. The effect of GPS on bile acid (BA) homeostasis, FXR expression, and liver inflammation were investigated. Second, the intestinal bacteria metabolites affected by GPS in vivo and in vitro were determined. The activation of FXR by sodium butyrate (NaB) was measured. Finally, the effects of NaB on cholestatic mice were demonstrated. The main pathways influenced by GPS involved BA biosynthesis. GPS upregulated hepatic FXR expression, improved BA homeostasis, reduced F4/80+ and Ly6G+ positive areas in the liver, and inhibited liver inflammation in cholestatic mice. Butyric acid was the most notable intestinal bacterial metabolite following GPS intervention. NaB activated the transcriptional activity of FXR in vitro, upregulated hepatic FXR and its downstream efflux transporter expression, and ameliorated disordered BA homeostasis in CLI mice. NaB inhibited the toll-like receptor 4/nuclear factor (TLR4/NF-κB) pathway and reduced inflammation and CLI in mice. An FXR antagonist suppressed the effects. In conclusion, GPS increased butyric acid production, which can activate hepatic FXR, reverse BA homeostasis disorder, and inhibit the TLR4/NF-κB inflammatory pathway, exerting protective effects against CLI.

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[This corrects the article DOI: 10.3389/fendo.2024.1338420.].

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Several investigators have reported that sarcopenia is common in patients with liver cirrhosis. However, few studies have probed the association between sarcopenia and liver cirrhosis complicated with oesophageal and gastric variceal bleeding (LC-EGVB). We aimed to investigate the impact of sarcopenia on rebleeding after endoscopic therapy in patients with LC-EGVB. Computed tomography (CT) radiographs from the third lumbar vertebra were selected to analyse body composition, including skeletal muscle tissue, visceral and subcutaneous adipose tissue using SliceOmatic software. Sarcopenia was defined using validated cutoff values for patients with liver cirrhosis: 44.77 cm2/m2 for men and 32.50 cm2/m2 for women. A total of 187 patients with LC-EGVB and 309 controls were included in this study. The rate of sarcopenia in controls (17.4%) was significantly lower than that in patients with LC-EGVB (41.2%). Patients with LC-EGVB exhibiting sarcopenia showed a high prevalence of portal vein thrombosis and rebleeding rate at 1 year. The rate of sarcopenia in the rebleeding group was significantly higher than that in the non-rebleeding group. Univariate and multivariate analyses showed that sarcopenia was an independent risk factor for rebleeding within 1 year in patients with LC-EGVB. Patients with LC-EGVB displayed a high prevalence of sarcopenia. Sarcopenia was observed to be an independent risk factor for rebleeding within 1 year.

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Scientific risk assessment of exogenous and endogenous toxic substances in traditional Chinese medicine (TCM) is of great significance. The present review comprises a comprehensive summary of progress in the health risk assessment of harmful exogenous substances in TCMs. Such substances include heavy metals, pesticide residues, biotoxins, and endogenous toxic components involving pyrrolizidine alkaloids. The review also discusses the strengths and weaknesses of various bioaccessibility and bioavailability models, and their applications in risk assessment. Future avenues of risk assessment research are highlighted, including further exploration of risk assessment parameters, innovation of bioaccessibility and bioavailability techniques, enhancement of probabilistic risk assessment combined with bioavailability, improvement of cumulative risk assessment strategies, and formulation of strategies for reducing relative bioavailability (RBA) values in TCMs. Such efforts represent an attempt to develop a risk assessment system that is capable of evaluating the exogenous and endogenous toxic substances in TCMs to ensure its safe use in clinics, and to promote the sustainable development of the TCM industry.