BACKGROUND:Intratumoral fibrosis influences treatment efficacy and prognosis of rectal cancer (RC). The roles of MR elastography (MRE) and Virtual MRE (VMRE) remain unclear in assessing it in RC. PURPOSE:To evaluate MRE for assessing intratumoral fibrosis in RC, identify optimal b-values for VMRE, and compare their diagnostic performance. STUDY TYPE:Prospective cohort. POPULATION:A total of 71 participants with pathologically confirmed RC (47 men; mean age, 62 ± 10 years). FIELD STRENGTH/SEQUENCES:3T, T2-weighted turbo-spin echo, contrast-enhanced T1-weighted gradient-recalled echo, Intravoxel incoherent motion (IVIM) (b = 0, 100, 200, 1000, 1500 s/mm2), and spin-echo MRE. ASSESSMENT:All participants were divided at a 7:3 ratio: subgroup 1 (N = 49) determined the optimal b-value combination and established the empirical relationship between shifted apparent diffusion coefficient (sADC) and VMRE (Vc, Vφ) based on IVIM, with MRE (c, φ) as reference; subgroup 2 (N = 22) validated this relationship. MRE and VMRE evaluated intratumoral fibrosis in 43 surgically diagnosed participants. STATISTICAL TESTS:Receiver operating characteristic (ROC), Pearson correlation, DeLong test. Bonferroni-adjusted p < 0.05 indicated statistical significance. RESULTS:The optimal combination of b-values was 0 and 1500 s/mm2 (r c = -0.808, r φ = -0.644) for VMRE in subgroup 1. In 43 surgically diagnosed participants, area under curves (AUCs) of c and φ for assessing intratumoral fibrosis were 0.779 and 0.684, respectively (Adjusted p = 0.828). AUCs of Vc and Vφ converted from sADC0-1500 values were 0.792 and 0.784, respectively (Adjusted p > 0.999). No significant differences in AUCs were observed among all parameters (Adjusted p: 0.384 to > 0.999). Sensitivity and specificity ranges of MRE and VMRE were 85.7%-90.5% and 54.5%-68.2%, respectively. DATA CONCLUSIONS:MRE was used to evaluate intratumoral fibrosis in RC. The optimal b-values combination for VMRE in RC was 0 s/mm2 and 1500 s/mm2. No significant difference was observed for assessing intratumoral fibrosis between MRE and VMRE. EVIDENCE LEVEL:2. TECHNICAL EFFICACY:Stage 2.

Background: Sepsis-related acute respiratory distress syndrome (ARDS) is a fatal disease without effective therapy. Kaempferol is a flavonoid compound extracted from natural plant products; it exerts numerous pharmacological effects. Kaempferol attenuates sepsis-related ARDS; however, the underlying protective mechanism has not been elucidated completely. Objective: This study aimed to use network pharmacology and experimental verification to investigate the mechanisms by which kaempferol attenuates sepsis-related ARDS. Methods: We screened the targets of kaempferol by PharMapper, Swiss Target Prediction, and CTD database. We identified the targets of sepsis-related ARDS by GeneCards, DisGeNet, OMIM, and TTD. The Weishengxin platform was used to map the targets of both kaempferol and sepsis-related ARDS. We created a Venn diagram to identify the intersection targets. We constructed the "component-intersection targets-disease" network diagram using Cytoscape 3.9.1 software. The intersection targets were imported into the STRING database for developing the protein-protein interaction network. Metascape was used for the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. We selected the leading 20 KEGG pathways to establish the KEGG relationship network. Finally, we performed experimental verification to confirm our prediction results. Results: Through database screening, we obtained 502, 360, and 78 kaempferol targets, disease targets of sepsis-related ARDS, and intersection targets, respectively. The core targets consisted of tumor necrosis factor-alpha (TNF-α), interleukin (IL)-6, albumin (ALB), IL-1β, and AKT serine/ threonine kinase (AKT)1. GO enrichment analysis identified 426 items, which were principally involved in response to lipopolysaccharide, regulation of inflammatory response, inflammatory response, positive regulation of cell migration, positive regulation of cell adhesion, positive regulation of protein phosphorylation, response to hormone, regulation of reactive oxygen species (ROS) metabolic process, negative regulation of apoptotic signaling pathway, and response to decreased oxygen levels. KEGG enrichment analysis identified 151 pathways. After eliminating the disease and generalized pathways, we obtained the hypoxia-inducible factor 1 (HIF-1), nuclear factor κB (NF-κB), and phosphoinositide 3-kinase (PI3K)-Akt signaling pathways. Our experimental verification confirmed that kaempferol blocked the HIF-1, NF-κB, and PI3K-Akt signaling pathways, diminished TNF-α, IL-1β, and IL-6 expressions, suppressed ROS production, and inhibited apoptosis in lipopolysaccharide (LPS)-induced murine alveolar macrophage (MH-S) cells. Conclusion: Kaempferol can reduce inflammatory response, ROS production, and cell apoptosis by acting on the HIF-1, NF-κB, and PI3K-Akt signaling pathways, thereby alleviating sepsis- related ARDS.

BackgroundMitochondrial dysfunction affects the development of ovarian cancer (OC). ETV4 is involved in mitochondrial fusion. The regulatory pathways of ETV4 in OC cells have not been further investigated. In this study, we aimed to explore the effects of ETV4 on OC development and analyze the downstream regulatory pathways of ETV4.MethodsThe expression of ETV4 in OC cell lines (SK-OV-3, HEY, A2780, and OVCAR-3) was verified. After silencing ETV4, indicators related to mitochondrial function, including ATP level, mitochondrial membrane potential, mitochondrial DNA (mtDNA), and mitochondrial ROS (mtROS), were analyzed. The expression of mitochondrial fission/fusion-related markers (Mfn1, Mfn2, OPA1, DRP1, MFF, and FIS1) was detected. In vivo experiments were used to verify the effect of ETV4 on OC development.ResultsThe TCGA-OV data indicated that ETV4 was highly expressed in OC. Silencing ETV4 inhibited the proliferation of OC cells. Mitochondrial membrane potential and ATP levels increased after ETV4 silencing, while mtDNA and mtROS levels decreased. ETV4 silencing promoted Mfn2 protein expression but did not affect Mfn2 mRNA level. Mfn2-associated E3 ubiquitin ligase MARCH9 was targeted and regulated by ETV4. MARCH9 overexpression alleviated the regulation of ETV4 silencing on mitochondrial function in OC cells. Lysosomal inhibitor CQ blocked the degradation of ubiquitinated Mfn2 protein. MARCH9 was found to mediate robust ubiquitination of Mfn2 via the K63-linked ubiquitination.ConclusionsETV4 was highly expressed in OC and involved in the regulation of mitochondrial function. ETV4 regulated Mfn2 ubiquitination linked by K63 by regulating MARCH9.

OBJECTIVES:Parkinson's disease (PD) has a complex genetic etiology, with autosomal recessive (AR) genes significantly contributing. This study uses next-generation sequencing (NGS) and long-read sequencing data (LRS) in Chinese AR-PD families to uncover novel genes, enhancing our genetic comprehension of PD. METHODS:We investigated 162 AR-PD families and 1570 sporadic early-onset PD patients, combining homozygous mapping and whole-exome sequencing (WES) to identify candidates. Using the GenoPriori-WeightSchem approach, we conducted population-based prioritization of candidate genes. We prioritized biallelic loss-of-function variants in the candidate gene pool. LRS dataset were analyzed to investigate genes with structural genomic variants. The identified candidates were further validated in 3947 PD cases from our in-house whole-genome sequencing (WGS) dataset, along with 3100 PD cases derived from the UK Biobank WES dataset. RESULTS:Analysis of WES data from 25 core AR-PD families revealed five candidate genes: ROBO1, LMBR1L, RIOX2, INTS2, and H6PD. The GenoPriori-WeightSchem approach highlighted an additional five candidate genes: SORL1, PSD2, BRD9, EPG5, and SH3PXD2A. Focusing on homozygous loss-of-function variants, indicative of severe genetic impact, we identified six genes in AR-PD families: LRPPRC, PPP1R1B, C1RL, LNPK, HSD11B1L, and PPP1R3E. LRS data from 38 families revealed a homozygous structure variant, a 6.3 kb deletion, in the COL24A1 gene. Finally, eight of the identified candidate genes were consistently associated with PD in two independent replication stages. CONCLUSIONS:Our study identified eight promising candidate genes using a large sample of AR-PD families, combining NGS and LRS data, which may expand the spectrum of candidate autosomal recessive genes responsible for PD. © 2025 International Parkinson and Movement Disorder Society.

BACKGROUND:The prognosis and survival rate of patients with head and neck squamous cell carcinoma (HNSCC) remain a serious public health concern. Therefore, elucidation of the underlying mechanisms responsible for the biological behavior of HNSCC is crucial for the development of effective treatment strategies. MATERIALS AND METHODS:In this study, we analyzed TCGA database and found that MAPK12 was overexpressed in tumor samples compared to normal samples, which was confirmed by microarray expression profiles, quantitative real-time polymerase chain reaction, and immunohistochemistry. RESULTS:Cell functional experiments, including the cell counting kit-8 assay, wound healing test, and transwell assay, revealed that MAPK12 overexpression increased the proliferation, invasion, and migration of HNSCC cells. A correlation was observed between MAPK12 expression and patient survival in HNSCC across several clinicopathological variables, including disease grade and stage. Analysis of immune-related functions demonstrated that HNSCC patients with low MAPK12 expression had a more favorable tumor immune microenvironment and better immunological functions. CONCLUSION:Collectively, our study identified for the first time that MAPK12 is upregulated in HNSCC, functioning as an oncogene, indicating a suppressive tumor immune microenvironment and poor prognosis since it could promote cancer cell proliferation, invasion, and migration. However, further studies are needed to gain a more comprehensive understanding of the role of MAPK12 in HNSCC and other tumor types.

Metabolic dysfunction‐associated steatotic liver disease [MASLD; previously known as nonalcoholic fatty liver disease (NAFLD)] is a prevalent chronic liver disorder strongly associated with aging, yet the mechanisms underlying age‐related hepatic lipid dysregulation remain incompletely defined. This study investigates how aging alters hepatic phospholipid metabolism and the contribution of phosphatidylethanolamine N‐methyltransferase (PEMT) to MASLD progression. Here, lipid accumulation was characterized in the livers of 2‐, 6‐, 12‐, 18‐, and 24‐month‐old mice, revealing age‐dependent increases in hepatic triacylglycerol (TG), total cholesterol (TC), and lipid droplet formation. Lipidomic analysis revealed a marked imbalance in phospholipid composition, characterized by increased phosphatidylcholine (PC) and decreased phosphatidylethanolamine (PE), resulting in a 2.5‐fold increase in the PC/PE ratio in 24‐month‐old mice compared with 6‐month‐old controls. Mechanistically, PEMT, a key enzyme regulating PC and PE metabolism, exhibited significantly increased expression (~2.4‐fold at the protein level) in aged livers, suggesting a pivotal role in driving the observed phospholipid imbalance in vitro . PEMT inhibition significantly attenuated lipid droplet accumulation by ~30% and reduced intracellular TG levels by ~20% in D‐galactose‐induced senescent AML12 hepatocytes under lipid stress, compared with nonsilenced senescent controls. These findings suggest that aging‐driven PEMT overexpression promotes phospholipid remodeling and hepatic lipid accumulation. By leveraging a natural aging mouse model, our study provides the first evidence linking PEMT activity to age‐associated phospholipid dyshomeostasis, revealing a previously unknown mechanistic axis distinct from diet‐induced MASLD and offering new therapeutic insights.

RATIONALE AND OBJECTIVES:The diagnostic value of traditional imaging methods and radiomics in predicting macrotrabecular-massive hepatocellular carcinoma (MTM HCC) is yet to be ascertained. Therefore, this meta-analysis aims to compare the diagnostic performance of radiomics and conventional imaging techniques for MTM HCC. MATERIALS AND METHODS:Comprehensive publications were searched in PubMed, Embase, Web of Science, and Cochrane Library up to 28 February 2025. Pooled sensitivity, specificity, positive likelihood ratio (PLR), and negative likelihood ratio (NLR) with 95% confidence interval (CI) were calculated for radiomics and non-radiomics methods using a bivariate random-effects model. Summary receiver operating characteristic (SROC) curves with the area under the curve (AUC) were generated to evaluate overall diagnostic performance. Meta-regression analysis was performed to explore potential sources of heterogeneity. Sensitivity analysis was conducted in radiomics model group, excluding training cohorts. Pairwise comparisons of sensitivity and specificity were performed between radiomic and non-radiomics groups. The 95% CIs of the AUCs of radiomics and non-radiomics groups were compared. RESULTS:A total of 20 eligible studies, including 1145 MTM HCC lesions and 2839 non-MTM HCC lesions were analyzed. The pooled sensitivity, specificity, and AUC were 0.87 (95%CI: 0.81-0.91, I2 = 63.60%), 0.78 (95%CI: 072-0.83, I2 = 77.28%), and 0.89 (95% CI: 0.86-0.91) for radiomics models. Conversely, the non-radiomics models had sensitivity and specificity of 0.62 (95%CI: 0.54-0.70, I2 = 71.78%) and 0.88 (95%CI: 0.82-0.92, I2 = 90.09%) and an AUC of 0.80 (95%CI: 0.77-0.84). Meta-regression analysis demonstrated that the tumor size and imaging modality affected the heterogeneity (P<0.001). Comparative analysis indicated significantly higher sensitivity for radiomics model group (P<0.001) and significantly higher specificity for non-radiomics model group (P=0.02). Radiomics model groups demonstrated a significant higher AUC than non-radiomics group due to nonoverlapping 95% CIs. CONCLUSION:Radiomics methods have potential advantages in preoperative MTM HCC prediction than non-radiomics methods due to higher sensitivity and AUC. Prospective multicenter validation and standardization of radiomics pipelines are needed to ensure its clinical application.

The efficacy of immunotherapy in colorectal cancer (CRC) hinges upon a comprehensive understanding of how the immune system interacts with tumor cells within the colorectal microenvironment. Mature tertiary lymphoid structures (mTLSs) are associated with an increased objective response rate, progression-free survival, and overall survival in patients with CRC. Thus, it has been suggested that increasing mTLSs in the context of CRC could improve patient outcomes. However, no established method to specifically induce TLS maturation within and around tumor sites is available. To address this gap in technology, we engineered a Salmonella typhimurium strain, SLCVNP20009, to express tumor necrosis factor (TNF) superfamily member 14 (TNFSF14, also called LIGHT). This strain colonized tumors and released LIGHT, which then formed a ligand-receptor pair with herpes virus entry mediator (HVEM) to induce a powerful cellular immune response. Furthermore, this engineered microbe modulated the proportions of intestinal innate lymphoid cells (ILCs), which serve an anti-infection role in innate immunity. Mice that were deficient in HVEM or ILC3 exhibited fewer mTLSs, a greater bacterial burden, and increased mortality in two different models of CRC. Thus, this engineered microbe with enhanced immunogenic properties demonstrated the potential to stimulate mTLS-associated antitumor immune responses in the colon and was well tolerated in vivo. Our results indicate that LIGHT-HVEM signaling on group 3 ILCs (ILC3s) is crucial for mTLS formation and T cell-mediated antitumor immunity in CRC and additionally suggest a synbiotic-based therapeutic approach for the management of CRC.

BackgroundTertiary lymphoid structures (TLS) within the tumor microenvironment have been associated with cancer prognosis and therapeutic response. However, the immunological pattern of a high peritumoral TLS (pTLS) density and its clinical potential in hepatocellular carcinoma (HCC) remain poor. This study aimed to elucidate biological differences related to pTLS density and develop a radiomic classifier for predicting pTLS density in HCC, offering new insights for clinical diagnosis and treatment.MethodsSpatial transcriptomics (n=4) and RNA sequencing data (n=952) were used to identify critical regulators of pTLS density and evaluate their prognostic significance in HCC. Baseline MRI images from 660 patients with HCC who had undergone surgery treatment between October 2015 and January 2023 were retrospectively recruited for model development and validation. This included training (n=307) and temporal validation (n=76) cohorts from Xiangya Hospital, and external validation cohorts from three independent hospitals (n=277). Radiomic features were extracted from intratumoral and peritumoral regions of interest and analyzed using machine learning algorithms to develop a predictive classifier. The classifier’s performance was evaluated using the area under the curve (AUC), with prognostic and predictive value assessed across four independent cohorts and in a dual-center outcome cohort of 41 patients who received immunotherapy.ResultsPatients with HCC and a high pTLS density experienced prolonged median overall survival (p<0.05) and favorable immunotherapy response (p=0.03). Moreover, immune infiltration by mature B cells was observed in the high pTLS density region. Spatial pseudotime analysis and immunohistochemistry staining revealed that expansion of pTLS in HCC was associated with elevated CXCL9 and CXCL10 co-expression. We developed an optimal radiomic-based classifier with excellent discrimination for predicting pTLS density, achieving an AUC of 0.91 (95% CI 0.87, 0.94) in the external validation cohort. This classifier also exhibited promising stratification ability in terms of overall survival (p<0.01), relapse-free survival (p<0.05), and immunotherapy response (p<0.05).ConclusionWe identified key regulators of pTLS density in patients with HCC and proposed a non-invasive radiomic classifier capable of assisting in stratification for prognosis and treatment.

Moringa oleifera seeds had shown multiple pharmacological properties and contained various chemical constituents. In a study focusing on the investigation of active compounds in M. oleifera seeds, four new compounds were isolated, including three benzyl alcohol compounds ( 1 - 3 ), and one benzyl thiocarbamate ( 4 ). Their structures were determined using comprehensive spectroscopic methods, such as ECD, 1D and 2D NMR experiments. The inhibitory activities of these compounds against lipopolysaccharide (LPS)-activated nitric oxide (NO) production in RAW 264.7 were evaluated in vitro. Compounds 1 - 3 demonstrated moderate inhibitory activities against LPS-activated NO production in RAW 264.7 cells. Furthermore, the potential anti-inflammatory mechanisms of compounds 1 - 3 were elucidated through target prediction and molecular docking analyses. Molecular docking analysis revealed that these compounds exhibited anti-inflammatory activity by antagonizing the MMP9 receptor. This study offers new insights for the development and utilization of M. oleifera seeds.

Intestinal stem cells (ISCs) initiate intestinal epithelial regeneration and tumorigenesis, and they experience rapid refilling upon various injuries for epithelial repair as well as tumor reoccurrence. It is crucial to reveal the mechanism underlying such plasticity for intestinal health. Recent studies have found that metabolic pathways control stem cell fate in homeostasis, but the role of metabolism in the regeneration of ISCs after damage has not been clarified. Here, we find that in a human colorectal cancer dataset, miR-29a and b (miR-29a/b) are metabolic regulators highly associated with intestinal tumorigenesis and worse prognostic value of radiotherapy. We also show that these two microRNAs are required for intestinal stemness maintenance in mice, and their expression is induced in regenerated ISCs after irradiation injury, resulting in skewed ISC fate from differentiation towards self-renewal. This upregulation of miR-29a/b expression in ISCs leads to suppression of fatty acid oxidation (FAO) and depression of oxidative phosphorylation, which in turn controls the balance between self-renewal and differentiation of ISCs. Deletion of miR-29a/b prevents these effects and thus impairs ISC-mediated epithelial recovery. Finally, we filter the potential targets of miR-29a/b and identify Hnf4g, a transcription factor, that drives this metabolic reprogramming through regulating FAO-related enzymes. Our work discovers an important metabolic mechanism of ISC-mediated regeneration and potentially pave the way for more targeted and effective therapeutic strategies for intestinal repair as well as tumor treatment.

BACKGROUND:Neuropathic pain is chronic and affects the patient's life. Studies have shown that IRF5 and CXCL13/CXCR5 are involved in neuropathic pain; however, their interactions are unknown. OBJECTIVE:In this study, a rat neuropathic pain model was constructed by inducing chronic compression injury (CCI). IRF5 recombinant lentiviral vector and CXCL13 neutralizing antibody were administered to investigate their action mechanisms in neuropathic pain. Consequently, the new strategies for disease treatment could be evolved. METHODS:The CCI rats were intrathecally injected with recombinant lentivirus plasmid LV-IRF5 (overexpression), LV-SH-IRF5 (silencing), and CXCL13 neutralizing antibody. Mechanical withdrawal threshold (MWT) and thermal withdrawal latency (TWL) were measured. The tumor necrosis factor (TNF)-alpha, interleukin (IL)-1β, and IL-6 levels were recorded via the enzyme-linked immunosorbent assay (ELISA). The spinal cord was stained using hematoxylin-eosin (HE). The binding of IRF5 to CXCL13 was analyzed by chromatin immunoprecipitation (ChIP) and dual luciferase reporter assay. The IRF5, neuronal nuclei (NeuN), CXCL13, and CXCR5 expressions were detected through quantitative real-time polymerase chain reaction and Western blot. RESULTS:The MWT and TWL values in the CCI group were lower than in the Sham group. The expressions of CXCL13, CXCR5, and IRF5 in CCI rats were gradually increased with the modeling time. IRF5 silencing suppressed the expression of NeuN and lumbar enlargement in CCI rats and promoted MWT and TWL. Moreover, IRF5 silencing inhibited the expressions of CXCR5 and CXCL13 genes and down-regulated the expression levels of inflammatory factors. IRF5 was directly and specifically bound with the endogenous CXCL13 promoter and thus regulated it. IRF5 overexpression exacerbated the disease phenotype of CCI-induced neuropathic pain in rats. Administration of CXCL13 neutralizing antibodies reversed the IRF5 overexpression effects. CONCLUSION:The IRF5 silencing alleviated neuropathic pain in CCI rats by downregulating the pain threshold, inflammatory cytokine levels, and CXCL13/CXCR5 signaling. IRF5 overexpression exacerbated the disease parameters of CCI-induced neuropathic pain in rats; however, they were reversed by neutralizing antibodies against CXCL13.

OBJECTIVES:Fibroblast activating protein (FAP) is associated with various organ fibrosis. However, the expression and molecular function of FAP in oral submucous fibrosis (OSF) is still unclear. MATERIALS AND METHODS:The high-performance liquid chromatography was used to detect the presence of alkaloids in areca nut extract (ANE). Real-time qPCR, Western blot, and Immunohistochemistry assay were used to analyze the expression of FAP mRNA or protein in OSF and normal oral tissue. A chi-squared test analyzed the relationship between FAP protein expression and clinicopathological data of OSF patients. CCK-8, Wound-healing, and Transwell migration assay were employed to assess the effect of the proliferation and migration ability of hOMF cells with FAP overexpression or knockdown. The expression level of a-SMA, FSP1, and P13K-Akt signaling pathways-related protein in hOMF cells transfected with FAP overexpression or knockdown plasmid was verified by western blot assay. RESULTS:The four specific areca alkaloids (Arecoline, Guvacine, Arecaidine, and Guvacoline) were successfully detected in the ANE. The viability of hOMF cells was significantly improved in the 50 μg/mL ANE group and was inhibited in the 5 and 50 mg/mL ANE groups. The expression of FAP was upregulated in OSF tissues, and hOMF cells treated with 50 μg/mL ANE and was related to pathology grade, clinical stage, and history of chewing betel nut. Additionally, FAP may promote the proliferation, migration, and activation of hOMF cells through the P13K-Akt signaling pathway. CONCLUSIONS:This study found that ANE had a bidirectional effect on the viability of hOMF cells, and the FAP gene was a potential therapeutic target in OSF.

BACKGROUND:Integrating vessels encapsulating tumor clusters (VETC) and microvascular invasion (MVI) (VM hereafter) is potentially useful in risk stratification of hepatocellular carcinoma (HCC). However, noninvasive assessment methods for VM are lacking. PURPOSE:To investigate the diagnostic performance of tomoelastography in assessing the VM status in HCC. STUDY TYPE:Retrospective. POPULATION:One hundred sixty-eight patients with surgically confirmed HCC consisting of 115 training and 53 validation cohorts, divided into negative-VM and positive-VM groups with mild or severe-VMs. Of them, 127 patients completed the follow-up (median: 26.1 months). FIELD STRENGTH/SEQUENCE:3D multifrequency tomoelastography with a single-shot spin-echo echo-planar imaging sequence, and liver MRI including T1-weighted in-phase and opposed-phase gradient echo (GRE), T2-weighted turbo spin echo, diffusion-weighted imaging and dynamic contrast-enhanced T1-weighted GRE sequences at 3.0 T. ASSESSMENT:Shear wave speed (c) and phase angle of the shear modulus (φ) were calculated on tomoelastograms. Imaging features were visually analyzed and clinical features were collected. Conventional models used clinical and imaging features while nomograms combined tomoelastography, clinical and imaging features. STATISTICAL TESTS:Univariable and multivariable logistic regression analyses, nomogram, area under the receiver operating characteristic curve (AUC), DeLong test, Kaplan-Meier analysis and log-rank test. P < 0.05 was considered statistically significant. RESULTS:Tumor-to-liver parenchyma ratio of c (cr) and tumor c were independent risk factors for positive-VM and severe-VM, respectively. In validation cohort, the nomograms including cr and tumor c performed significantly better than the conventional models for diagnosing positive-VM (0.84 [95% CI: 0.72-0.93] vs. 0.77 [95% CI: 0.64-0.88]) and severe-VM (0.86 [95% CI: 0.68-0.96] vs. 0.75 [95% CI: 0.55-0.89]). Patients with estimated positive-VM (9.3 months)/severe-VM (9.2 months) based on nomograms had shorter median recurrence-free survival than those with estimated negative-VM (>20.0 months)/mild-VM (18.0 months) in validation cohort. DATA CONCLUSION:Tomoelastography based-nomograms showed good performance for noninvasively assessing VM status in patients with HCC. EVIDENCE LEVEL:3 TECHNICAL EFFICACY: Stage 2.

Oral squamous cell carcinoma (OSCC) affects a large number of individuals worldwide. Despite advancements in surgery, radiation, and chemotherapy, satisfactory outcomes have not been achieved. In recent years, the success of drugs targeting programmed cell death 1 (PD-1) and programmed cell death ligand 1 (PD-L1) has led to breakthroughs in cancer treatment, but systematic summaries on their effectiveness against OSCC are lacking. This article reviews the latest research on the PD-1/PD-L1 pathway and the potential of combination therapy based on this pathway in OSCC. Further, it explores the mechanisms involved in the interaction of this pathway with exosomes and protein-protein interactions, and concludes with potential future OSCC therapeutic strategies.

The homeostasis of the microbiota is essential for human health. In particular, the gut microbiota plays a critical role in the regulation of the immune system. Thus, faecal microbiota transplantation (FMT), a technology that has rapidly developed in the last decade, has specifically been utilised for the treatment of intestinal inflammation and has recently been found to be able to treat tumours in combination with immunotherapy. FMT has become a breakthrough in enhancing the response rate to immunotherapy in cancer patients by altering the composition of the patient's gut microbiota. This review discusses the mechanisms of faecal microorganism effects on tumour development, drug treatment efficacy, and adverse effects and describes the recent clinical research trials on FMT. Moreover, the factors influencing the efficacy and safety of FMT are described. We summarise the possibilities of faecal transplantation in the treatment of tumours and its complications and propose directions to explore the development of FMT.

BACKGROUND The role of inflammation in the pathogenesis of type 2 diabetes mellitus (T2DM) is well established. Lyn, a member of the nonreceptor protein tyrosine kinase Src family, has been reported to modulate inflammatory signaling pathways. METHODS Lyn expression was assessed in kidney biopsies of 11 patients with diabetic kidney disease (DKD) and in kidney tissues of streptozotocin (STZ)-induced DKD mice. 102 recruited T2DM patients were divided into three groups: normoalbuminuria, microalbuminuria and macroalbuminuria. Twenty-one healthy volunteers were recruited as a control group. Clinical data, blood and urine samples of all individuals were collected for analysis. RESULTS Lyn expression was augmented in the kidneys of DKD patients and STZ-induced diabetic mice. Compared with control and normoalbuminuria groups, both mRNA and protein expression of Lyn in peripheral blood mononuclear cells (PBMCs) in the macroalbuminuria group were significantly increased (p < .05). Elevated Lyn levels were independently related to urine albumin/urine creatinine ratio and were positively associated with key inflammatory factors, namely interleukin-1β, monocyte chemoattractant protein-1, and tumor necrosis factor-α. Additionally, Lyn exhibited a noteworthy connection with renal tubular injury indicators, specifically urinary neutrophil gelatinase-associated lipocalin and urinary retinol binding protein. ROC curve analysis showed that Lyn could predict albuminuria in diabetic patients with an area under the curve of 0.844 (95% CI: 0.764-0.924). CONCLUSION Lyn levels in PBMCs exhibited a positive correlation with the severity of albuminuria, renal tubular damage, and inflammatory responses. Hence, Lyn may be a compelling candidate for predicting albuminuria levels in diabetes.