Developments of electrospinning technology in membrane bioreactor: A Review.

The necessity for effective wastewater treatment and purification has grown as a result of the increasing pollution issues brought on by industrial and municipal wastewater. Membrane bioreactor (MBR) technology stands out when compared to other treatment methods because of its high efficiency, environmental friendliness, small footprint, and ease of maintenance. However, the development and application of membrane bioreactors has been severely constrained by the higher cost and shorter service life of these devices brought on by membrane biofouling issues resulting from contaminants and bacteria in the water. The nanoscale size of the electrospinning products provides unique microstructure, and the technology facilitates the production of structurally different membranes, or the modification and functionalization of membranes, which makes it possible to solve the membrane fouling problem. Therefore, many current studies have attempted to use electrospinning in MBRs to address membrane fouling and ultimately improve treatment efficacy. Meanwhile, in addition to solving the problem of membrane fouling, the fabrication technology of electrospinning also shows great advantages in constructing thin porous fiber membrane materials with controllable surface wettability and layered structure, which is helpful for the performance enhancement of MBR and expanding innovation. This paper systematically reviews the application and research progress of electrospinning in MBRs. Firstly, the current status of the application of electrospinning technology in various MBRs is introduced, and the relevant measures to solve the membrane fouling based on electrospinning technology are analyzed. Subsequently, some new types of MBRs and new application areas developed with the help of electrospinning technology are introduced. Finally, the limitations and challenges of merging the two technologies are presented, and pertinent recommendations are provided for future research on the use of electrospinning technology in membrane bioreactors.

Chiral whispering gallery modes and chirality-dependent symmetric optical force induced by a spin-polarized surface wave of photonic Dirac semimetal.

Dirac degeneracy is a fourfold band crossing point in a three-dimensional momentum space, which possesses Fermi-arc-like surface states, and has extensive application prospects. In this work, we systematically study the exceptional effects of the robust chiral surface wave supported by photonic Dirac semimetal acts on the dielectric particles. Theoretical results show that orthogonal electromagnetic modes and helical or chiral whispering gallery modes (WGMs) of dielectric particles can be efficiently excited by the unidirectional spin-polarized surface wave. More importantly, optical forces exerted by the spin-polarized surface wave exhibit chirality-dependent symmetric behavior and high chiral Q factor with precise size selectivity. Our findings may provide potential applications in the area of chiral microcavity, spin optical devices, and optical manipulations.

Novel insights into the heterogeneity of FOXP3 + Treg cells in drug-induced allergic reactions through single-cell transcriptomics.

This study uncovers the novel heterogeneity of FOXP3 + regulatory T (Treg) cells and their pivotal role in modulating immune responses during drug-induced allergic reactions, employing cutting-edge single-cell transcriptomics. We established a mouse model for drug-induced allergic reactions and utilized single-cell RNA sequencing (scRNA-seq) to analyze the transcriptomic landscapes of FOXP3 + Treg cells isolated from affected tissues. The study involved both in vitro and in vivo approaches to evaluate the impact of FOXP3 expression levels on the immunoregulatory functions of Treg cells during allergic responses. Techniques included flow cytometry, cluster analysis, principal component analysis (PCA), CCK8 and CSFE assays for cell proliferation, LDH release assays for toxicity, ELISA for cytokine profiling, and CRISPR/Cas9 technology for gene editing. Our findings revealed significant transcriptomic heterogeneity among FOXP3 + Treg cells in the context of drug-induced allergic reactions, with distinct subpopulations exhibiting unique gene expression profiles. This heterogeneity suggests specialized roles in immune regulation. We observed a decrease in the proliferative capacity and cytokine secretion of FOXP3 + Treg cells following allergic stimulation, alongside an increase in reaction toxicity. Manipulating FOXP3 expression levels directly influenced these outcomes, where FOXP3 deletion exacerbated allergic responses, whereas its overexpression mitigated them. Notably, in vivo experiments demonstrated that FOXP3 overexpression significantly reduced the severity of allergic skin reactions in mice. Our study presents novel insights into the heterogeneity and crucial immunoregulatory role of FOXP3 + Treg cells during drug-induced allergic reactions. Overexpression of FOXP3 emerges as a potential therapeutic strategy to alleviate such allergic responses. These findings contribute significantly to our understanding of immune regulation and the development of targeted treatments for drug-induced allergies.

Adsorption mechanism of hexavalent chromium on electron beam-irradiated aged microplastics: Novel aging processes and environmental factors.

Microplastics are widely present in the natural environment and exhibit a strong affinity for heavy metals in water, resulting in the formation of microplastics composite heavy metal pollutants. This study investigated the adsorption of heavy metals by electron beam-aged microplastics. For the first time, electron beam irradiation was employed to degrade polypropylene, demonstrating its ability to rapidly age microplastics and generate a substantial number of oxygen-containing functional groups on aged microplastics surface. Adsorption experiments revealed that the maximum adsorption equilibrium capacity of hexavalent chromium by aged microplastics reached 9.3 mg g-1. The adsorption process followed second-order kinetic model and Freundlich model, indicating that the main processes of heavy metal adsorption by aged microplastics are chemical adsorption and multilayer adsorption. The adsorption of heavy metals on aged microplastics primarily relies on the electrostatic and chelation effects of oxygen-containing functional groups. The study results demonstrate that environmental factors, such as pH, salinity, coexisting metal ions, humic acid, and water matrix, exert inhibitory effects on the adsorption of heavy metals by microplastics. Theoretical calculations confirm that the aging process of microplastics primarily relies on hydroxyl radicals breaking carbon chains and forming oxygen-containing functional groups on the surface. The results indicate that electron beam irradiation can simultaneously oxidize and degrade microplastics while reducing hexavalent chromium levels by approximately 90%, proposing a novel method for treating microplastics composite pollutants. Gas chromatography-mass spectrometry analysis reveals that electron beam irradiation can oxidatively degrade microplastics into esters, alcohols, and other small molecules. This study proposes an innovative and efficient approach to treat both microplastics composite heavy metal pollutants while elucidating the impact of environmental factors on the adsorption of heavy metals by electron beam-aged microplastics. The aim is to provide a theoretical basis and guidance for controlling microplastics composite pollution.

Role of aryl hydrocarbon receptors in infection and inflammation.

The aryl hydrocarbon receptor (AhR) is a transcription factor that is activated by various ligands, including pollutants, microorganisms, and metabolic substances. It is expressed extensively in pulmonary and intestinal epithelial cells, where it contributes to barrier defense. The expression of AhR is pivotal in regulating the inflammatory response to microorganisms. However, dysregulated AhR expression can result in endocrine disorders, leading to immunotoxicity and potentially promoting the development of carcinoma. This review focuses on the crucial role of the AhR in facilitating and limiting the proliferation of pathogens, specifically in relation to the host cell type and the species of etiological agents involved in microbial pathogen infections. The activation of AhR is enhanced through the IDO1-AhR-IDO1 positive feedback loop, which is manipulated by viruses. AhR primarily promotes the infection of SARS-CoV-2 by inducing the expression of angiotensin-converting enzyme 2 (ACE2) and the secretion of pro-inflammatory cytokines. AhR also plays a significant role in regulating various types of T-cells, including CD4+ T cells and CD8+ T cells, in the context of pulmonary infections. The AhR pathway plays a crucial role in regulating immune responses within the respiratory and intestinal barriers when they are invaded by viruses, bacteria, parasites, and fungi. Additionally, we propose that targeting the agonist and antagonist of AhR signaling pathways could serve as a promising therapeutic approach for combating pathogen infections, especially in light of the growing prevalence of drug resistance to multiple antibiotics.

Establishment and validation of a tumor-infiltrating γδT cell related prognostic gene signature in head and neck squamous cell carcinoma.

γδT cells are unconventional T cells only accounting for 1-5 % of circulating T lymphocytes. Their potent anti-tumor capability has been evidenced by accumulating studies. However, the prognostic value of γδT cells remains not well documented in head and neck squamous cell carcinoma (HNSCC). In this study, we utilized the TCGA HNSCC database to evaluate the infiltration of γδT cells and the association between γδT cells and clinicopathological factors by related gene signature, which were then validated by a total of 100 collected tumor samples from HNSCC patient cohort. Heterogeneity and functional characteristics of distinct infiltrating γδT cell profiles in HNSCC were then investigated based on the scRNA-seq data from the GEO database. We found higher γδT cell gene signature score was significantly associated with longer survival. Cox regression models showed that γδT cell gene signature could serve as an independent prognostic indicator for HNSCC patients. A high level of γδT cell-related gene signature was positively correlated with the infiltration of tumor-infiltrating lymphocytes and immune score. Through scRNA-seq analysis, we identified that γδ+ Trm cells and γδ+ CTL cells possessed anti-tumor and immunoregulatory properties. Notably, we found a significant association between the presence of these cells and improved survival outcomes. In our cell-cell communication analyses, we identified that γδT cells have the potential to eliminate tumor cells through the secretion of interferon-gamma and granzyme. Collectively, the infiltration of γδT cells may serve as a promising prognostic tool, prompting the consideration of treatment options for patients with HNSCC.

The efficacy and safety of stereotactic body radiotherapy combined with systematic therapy for metastatic renal cell carcinoma: a systematic review and meta-analysis.

There is considerable interest in the potential of stereotactic body radiation therapy (SBRT) combined with systemic therapy such as tyrosine kinase inhibitors (TKIs) or immune checkpoint inhibitors (ICIs). However, its efficacy and safety remain unclear. The purpose of this study was to evaluate the efficacy and safety of conducting SBRT during ICI or TKI treatment in different disease settings for patients with metastatic renal cell carcinoma (mRCC). A total of 16 studies were ultimately included. Under the random effects model, the pooled 1-year local control rate (1-yr LCR) and objective response rate (ORR) were 90% (95% confidence interval [CI]: 80%-95%, I 2 = 67%) and 52% (95% CI: 37%-67%, I 2 = 90%), respectively. SBRT concomitant with different systemic therapy yield significant different 1-yr LCR (p < 0.01) and ORR (p = 0.02). Regarding survival benefits, the pooled 1-year progression-free survival (1-yr PFS) and 1-year overall survival (1-yr OS) rates were 45% (95% CI: 29%-62%, I 2 = 91%) and 85% (95% CI: 76%-91%, I 2 = 66%), respectively. 1-yr PFS and 1-yr OS in different disease settings demonstrated significant difference (p < 0.01). As for toxicity, the pooled incidence of grade 3-4 adverse events was 14% (95% CI: 5%-26%, I 2 = 90%). This study highlights the feasibility of utilizing these strategies in mRCC patients, especially those with a low metastatic tumor burden.

So many measures in ERAS protocol: Which matters most?

OBJECTIVES: Enhanced recovery after surgery (ERAS), which includes multiple measures, has gradually become the standard perioperative management in pediatric surgery. However, it is still unclear which of its many measures affects the outcomes more. METHODS: We retrospectively analyzed the medical records of children with congenital choledochal cysts who underwent surgical treatment in a specialized children's hospital from January 2019 to December 2022. Data including baseline factors, implementation of ERAS interventions, postoperative complications, and postoperative length of stay (PLOS) were collected. Univariate and multivariate analyses were performed to identify the association between PLOS and baseline factors or specific ERAS measures. RESULTS: The implementation rate of ERAS measures ranged from 5.02% to 100% in 219 cases who underwent 3 to 14 ERAS measures. Univariate analysis showed that body mass index-for-age z-scores, liver function indicators, and postoperative complications were the significant baseline factors for PLOS. At the same time, the measures with the greatest effect on PLOS were early postoperative feeding and early removal of tubes. Multivariate analysis with different models revealed that postoperative complications, early postoperative feeding, and early catheter removal influenced the PLOS the most. CONCLUSIONS: A prolonged PLOS was associated with poor preoperative nutritional status, elevated liver function indexes, and postoperative complications. Early postoperative feeding and removal of tubes appeared more likely with a reduced PLOS than other measures, requiring more attention when implementing the ERAS protocol.

Bio-inspired, sensitivity-enhanced, bi-directional airflow sensor for turbulence detection.

Detecting airflow turbulence precursors promptly is crucial for ensuring flight safety and control. The initial stages of turbulence involve small reverse flows with random velocities and directions, which are not easily detected by existing airflow sensors. In this study, we designed a bionic, sensitivity-enhanced, bi-directional airflow sensor (BSBA) by incorporating bio-inspired circular tip slits and enlarging the central part of the cruciform beam structure. The BSBA exhibits a rapid response time (24.1 ms), high sensitivity (1.36 mV m-1 s-1), consistent detection of forward and backward airflow (correlation coefficient of 0.9854), and a low airflow detection threshold (1 ml). With these features, the proposed sensor can rapidly and accurately measure slight variations in the oscillating airflow, flow field, and contact force. The BSBA also achieves transparent obstacle detection on a quadrotor, even in visually challenging environments, by capturing minute changes in the flow fields produced by the quadrotor when encountering obstacles. The sensor's high sensitivity, consistent bi-directional detection, and fast response give it significant potential for enhancing safety in aircraft control systems.

Single-cell transcriptomics reveals cell atlas and identifies cycling tumor cells responsible for recurrence in ameloblastoma.

Ameloblastoma is a benign tumor characterized by locally invasive phenotypes, leading to facial bone destruction and a high recurrence rate. However, the mechanisms governing tumor initiation and recurrence are poorly understood. Here, we uncovered cellular landscapes and mechanisms that underlie tumor recurrence in ameloblastoma at single-cell resolution. Our results revealed that ameloblastoma exhibits five tumor subpopulations varying with respect to immune response (IR), bone remodeling (BR), tooth development (TD), epithelial development (ED), and cell cycle (CC) signatures. Of note, we found that CC ameloblastoma cells were endowed with stemness and contributed to tumor recurrence, which was dominated by the EZH2-mediated program. Targeting EZH2 effectively eliminated CC ameloblastoma cells and inhibited tumor growth in ameloblastoma patient-derived organoids. These data described the tumor subpopulation and clarified the identity, function, and regulatory mechanism of CC ameloblastoma cells, providing a potential therapeutic target for ameloblastoma.

CYTOR Facilitates Formation of FOSL1 Phase Separation and Super Enhancers to Drive Metastasis of Tumor Budding Cells in Head and Neck Squamous Cell Carcinoma.

Tumor budding (TB) is a small tumor cell cluster with highly aggressive behavior located ahead of the invasive tumor front. However, the molecular and biological characteristics of TB and the regulatory mechanisms governing TB phenotypes remain unclear. This study reveals that TB exhibits a particular dynamic gene signature with stemness and partial epithelial-mesenchymal transition (p-EMT). Importantly, nuclear expression of CYTOR is identified to be the key regulator governing stemness and the p-EMT phenotype of TB cells, and targeting CYTOR significantly inhibits TB formation, tumor growth and lymph node metastasis in head and neck squamous cell carcinoma (HNSCC). Mechanistically, CYTOR promotes tumorigenicity and metastasis of TB cells by facilitating the formation of FOSL1 phase-separated condensates to establish FOSL1-dependent super enhancers (SEs). Depletion of CYTOR leads to the disruption of FOSL1-dependent SEs, which results in the inactivation of cancer stemness and pro-metastatic genes. In turn, activation of FOSL1 promotes the transcription of CYTOR. These findings indicate that CYTOR is a super-lncRNA that controls the stemness and metastasis of TB cells through facilitating the formation of FOSL1 phase separation and SEs, which may be an attractive target for therapeutic interventions in HNSCC.

P53: A Key Target in the Development of Osteoarthritis.

Osteoarthritis (OA), a chronic degenerative disease characterized mainly by damage to the articular cartilage, is increasingly relevant to the pathological processes of senescence, apoptosis, autophagy, proliferation, and differentiation of chondrocytes. Clinical strategies for osteoarthritis can only improve symptoms and even along with side effects due to age, sex, disease, and other factors. Therefore, there is an urgent need to identify new ideas and targets for current clinical treatment. The tumor suppressor gene p53, which has been identified as a potential target for tumor therapeutic intervention, is responsible for the direct induction of the pathological processes involved in OA modulation. Consequently, deciphering the characteristics of p53 in chondrocytes is essential for investigating OA pathogenesis due to p53 regulation in an array of signaling pathways. This review highlights the effects of p53 on senescence, apoptosis, and autophagy of chondrocytes and its role in the development of OA. It also elucidates the underlying mechanism of p53 regulation in OA, which may help provide a novel strategies for the clinical treatment of OA.

Quantifying mitochondrial heteroplasmy diversity: A computational approach.

Biodiversity plays a pivotal role in sustaining ecosystem processes, encompassing diverse biological species, genetic types and the intricacies of ecosystem composition. However, the precise definition of biodiversity at the individual level remains a challenging endeavour. Hill numbers, derived from Rényi's entropy, have emerged as a popular measure of diversity, with a recent unified framework extending their application across various levels, from genetics to ecosystems. In this study, we employ a computational approach to exploring the diversity of mitochondrial heteroplasmy using real-world data. By adopting Hill numbers with q = 2, we demonstrate the feasibility of quantifying mitochondrial heteroplasmy diversity within and between individuals and populations. Furthermore, we investigate the alpha diversity of mitochondrial heteroplasmy among different species, revealing heterogeneity at multiple levels, including mitogenome components and protein-coding genes (PCGs). Our analysis explores large-scale mitochondrial heteroplasmy data in humans, examining the relationship between alpha diversity at the mitogenome components and PCGs level. Notably, we do not find a significant correlation between these two levels. Additionally, we observe significant correlations in alpha diversity between mothers and children in blood samples, exceeding the reported R2 value for allele frequency correlations. Moreover, our investigation of beta diversity and local overlay similarity demonstrates that heteroplasmy variant distributions in different tissues of children more closely resemble those of their mothers. Through systematic quantification and analysis of mitochondrial heteroplasmy diversity, this study enhances our understanding of heterogeneity at multiple levels, from individuals to populations, providing new insights into this fundamental dimension of biodiversity.

Non-Calcifying/Langerhans Cell-Rich Calcifying Epithelial Odontogenic Tumour: A Critical Review of the Rare and Distinctive Entity.

BACKGROUND: The study aims to analyse the non-calcifying/Langerhans cell rich (NCLC) subtype of calcifying epithelial odontogenic tumour (CEOT).  METHOD: The features of cases of the NCLC subtype of CEOT noted in the English literature by PubMed as well as 3 new cases were reviewed. RESULTS: Overall, twenty-one cases were noted. Many were women in the fourth to sixth decades (male-to-female ratio =1 to 2). Radiologically, the lesion is often unilocular with resorption of the affected teeth. Nineteen of the 21 cases occurred in the maxilla, especially the anterior portion. On pathological examination, epithelial cells are noted in non-calcifying amyloid-rich fibrous stroma. The main differential diagnosis is the amyloid subtype of central odontogenic fibroma. Immunohistochemical studies revealed the tumour epithelial cells were positive for cytokeratins and p63 and contained CD1a, S-100, and langerin-positive Langerhans cells. On a median follow-up of 2 years, one patient had a recurrence one year after curettage. CONCLUSION: The NCLC subtype of CEOT is unique as it contains significant numbers of Langerhans cells and has clinicopathological features distinctive from classic CEOT.

Structure-Based Design and Synthesis of Potent and Selective KRAS G12D Inhibitors.

KRAS G12D mutation has been found in approximately 45% of pancreatic ductal adenocarcinoma (PDAC) cases, making it an attractive therapeutic target. Through structure-based drug design, a series of potent and selective KRAS G12D inhibitors were designed. The lead compound, ERAS-5024, inhibited ERK1/2 phosphorylation and cell proliferation in three-dimensional Cell-Titer Glo assays in AsPC-1 PDAC cells with single-digit nanomolar potency and caused tumor regression in the in vivo efficacy studies. We describe here the details of the design and synthesis program that led to the discovery of ERAS-5024.

Targeting BRD4 attenuates the stemness and aggressiveness of ameloblastoma.

BACKGROUND: BRD4, belonging to the bromodomain extra-terminal (BET) protein family, plays a unique role in tumor progression. However, the potential impact of BRD4 in ameloblastoma (AM) remains largely unknown. Herein, we aimed to assess the expression and functional role of BRD4 in AM. METHODS: The expression level of BRD4 was assessed by immunohistochemistry. The proliferation, migration, invasion, and tumorigenic abilities of AM cells were assessed by a series of assays. To explore the molecular expression profile of BRD4-depleted AM cells, RNA sequencing (RNA-seq) was performed. Bioinformatic analysis was performed on AM expression matrices obtained from the Gene Expression Omnibus (GEO). The therapeutic efficacy of BET-inhibitors (BETi) was assessed with AM patient-derived organoids. RESULTS: Upregulation of BRD4 was observed in conventional AMs, recurrent AMs, and ameloblastic carcinomas. Depletion of BRD4 inhibited proliferation, invasion, migration, and tumorigenesis in AM. Administration of BETi attenuated the aggressiveness of AM and the growth of AM patient-derived organoids. Bioinformatic analysis indicated that BRD4 may promote AM progression by regulating the Wnt pathway and stemness-associated pathways. CONCLUSION: BRD4 increases the aggressiveness and promotes the recurrence of ameloblastoma by regulating the Wnt pathway and stemness-associated pathways. These findings highlight BRD4 as a promising therapeutic target in AM management.

Deficiency of SR-B1 reduced the tumor load of colitis-induced or APCmin /+ -induced colorectal cancer.

BACKGROUND: Colorectal cancer (CRC) is one of the most common tumors in the world. Cholesterol plays an important role in the pathogenesis of tumors. One of the cholesterol transporters, scavenger receptor class B type 1 (SR-B1), a multi-ligand membrane receptor protein, is expressed in the intestines which also highly expressed in various tumors. But the potential mechanism of SR-B1 in CRC development has not been reported. AIMS: This study aimed to clarify the importance of SR-B1 in the development and prognosis of CRC as much as possible to provide a possible strategy in CRC treatment. MATERIALS & METHODS: In this study, we used SR-B1 gene knockdown mice to study the effect of SR-B1 on colitis-induced or APCmin/+ -induced CRC. The expression of related molecules were detected through the immunohistochemistry and hematoxylin-eosin staining, western blot analysis, and Flow cytometry. The gene expression and microbiota in microenvironment of CRC mice were analyzed through eukaryotic mRNA sequencing and 16S rRNA high-throughput sequencing. RESULTS: The results showed that SR-B1 knockdown reduced the tumor load of colitis-induced or APCmin/+ -induced CRC. SR-B1 knockdown improved the immune microenvironment by affecting the level of tumor-associated macrophage (TAM), mononuclear myeloid-derived suppressor cells (M-MDSCs), granulocytic myeloid-derived suppressor cells (G-MDSCs), programmed cell death-ligand 1 (PD-L1), and human leukocyte antigen class I-B (HLA-B), and also reduced the level of low-density lipoprotein receptor (LDL-R), and increased the level of ATP binding cassette transporter A1 (ABCA1) to regulate the cholesterol metabolism, and regulated the expression of related genes and intestinal microbiota. SR-B1 knockdown can also trigger the anti-CRC effect of anti-PD 1 in colitis-induced CRC. DISCUSSION: SR-B1 deficiency significantly improved the immunity in tumor microenvironment of colitis-induced or APCmin/+ -induced CRC. In addition, the microbiota changes caused by SR-B1 deficiency favor improving the immune response to chemotherapeutic drugs and anti-PD1 therapy. The mechanism of action of SR-B1 deficiency on the development of CRC still needs further in-depth research. CONCLUSION: This study provides a new treatment strategy for treating CRC by affecting the expression of SR-B1 in intestine.

Correlation between KRAS Mutation and CTLA-4 mRNA Expression in Circulating Tumour Cells: Clinical Implications in Colorectal Cancer.

Combination strategies of KRAS inhibition with immunotherapy in treating advanced or recurrent colorectal carcinoma (CRC) may need to be assessed in circulating tumour cells (CTCs) to achieve better clinical outcomes. This study aimed to investigate the genomic variations of KRAS in CTCs and matched CRC tissues and compared mRNA expression of KRAS and CTLA-4 between wild-type and KRAS-mutated CTCs and CRC tissues. Clinicopathological correlations were also compared. Six known mutations of KRAS were identified at both codon 12 and codon 13 (c.35G>T/G12V, c.35G>A7/G12D, c.35G>C/G12A, c.34G>A/G12S, c.38G>C/G13A, and c.38G>A/G13D). Three CTC samples harboured the identified mutations (16.7%; 3/18), while fifteen matched primary tumour tissues (65.2%, 15/23) showed the mutations. CTCs harbouring the KRAS variant were different from matched CRC tissue. All the mutations were heterozygous. Though insignificant, CTLA-4 mRNA expression was higher in patients carrying KRAS mutations. Patients harbouring KRAS mutations in CTCs were more likely to have poorly differentiated tumours (p = 0.039) and with lymph node metastasis (p = 0.027) and perineural invasion (p = 0.014). KRAS mutations in CTCs were also significantly correlated with overall pathological stages (p = 0.027). These findings imply the genetic basis of KRAS with immunotherapeutic target molecules based on a real-time platform. This study also suggests the highly heterogeneous nature of cancer cells, which may facilitate the assessment of clonal dynamics across a single patient's disease.

Prognostic scores in primary biliary cholangitis patients with advanced disease.

BACKGROUND: Due to the chronic progressive disease characteristics of primary biliary cholangitis (PBC), patients with advanced PBC should not be ignored. Most prognostic score studies have focused on early stage PBC. AIM: To compare the prognostic value of various risk scores in advanced PBC to help PBC patients obtain more monitoring and assessment. METHODS: This study considered patients diagnosed with PBC during hospitalization between 2015 and 2021. The clinical stage was primarily middle and late, and patients usually took ursodeoxycholic acid (UDCA) after diagnosis. The discriminatory performance of the scores was assessed with concordance statistics at baseline and after 1 year of UDCA treatment. Telephone follow-up was conducted to analyze the course and disease-associated outcomes. The follow-up deadline was December 31, 2021. We compared the risk score indexes between those patients who reached a composite end point of death or liver transplantation (LT) and those who remained alive at the deadline. The combined performance of prognostic scores in estimating the risk of death or LT after 1 year of UDCA treatment was assessed using Cox regression analyses. Predictive accuracy was evaluated by comparing predicted and actual survival through Kaplan-Meier analyses. RESULTS: We included 397 patients who were first diagnosed with PBC during hospitalization and received UDCA treatment; most disease stages were advanced. After an average of 6.4 ± 1.4 years of follow-up, 82 patients had died, and 4 patients had undergone LT. After receiving UDCA treatment for 1 year, the score with the best discrimination performance was the Mayo, with a concordance statistic of 0.740 (95% confidence interval: 0.690-0.791). The albumin-bilirubin, GLOBE, and Mayo scores tended to overestimate transplant-free survival. Comparing 7 years of calibration results showed that the Mayo score was the best model. CONCLUSION: The Mayo, GLOBE, UK-PBC, and ALBI scores demonstrated comparable discriminating performance for advanced stage PBC. The Mayo score showed optimal discriminatory performance and excellent predictive accuracy.