To develop a simple scoring system based on baseline inflammatory and nutritional markers to predict the long-term prognosis of patients with nasopharyngeal carcinoma (NPC). Conducted a retrospective analysis of clinical data from 1024 newly diagnosed non-metastatic NPC patients. A total of 15 pre-treatment inflammatory and nutritional markers were collected as candidate variables. Receiver operating characteristic (ROC) curves were used to determine the optimal cutoff points for each parameter. Survival analysis was performed using Kaplan-Meier method and Cox regression analysis. Besides, the Inflammation Nutrition Risk Score (INRS) was calculated for each patient by assigning each independent prognostic factor a score of 1. Multivariate Cox regression analysis showed that serum albumin (ALB), systemic immune-inflammation index, and monocyte count (M) were independent prognostic factors for OS (P < 0.05). Survival analysis showed that higher INRS was associated with a worsened prognosis. Patients in the high-risk group had shorter OS than in the low-risk group. In the training group, the 3-, 5-, and 8-years OS rates for the low-risk group versus high-risk group were 92.5% versus 87.8%, 87.4% versus 75.1%, and 84.6% versus 62.2%, respectively (P < 0.05). In the validation group, the 3-, 5-, and 8-years OS rates for the low-risk group vs. high-risk group were 95.0% versus 86.4%, 92.1% versus 82.2%, and 89.5% versus 74.3%, respectively (P < 0.05). Further subgroup analysis showed a significant difference in the OS between the high-risk group and low-risk group in patients with locally advanced disease (P < 0.05). The ROC curve demonstrated that INRS had a similar predictive value for long-term survival in NPC patients compared to TNM staging and serum EBV-DNA levels. Pretreatment ALB, M, and SIRI are independent prognostic factors for long-term survival in patients with NPC. INRS constructed based on these three factors can serve as a long-term prognostic indicator for NPC.

Hepatocyte growth factor (HGF) and its receptor, c-Met, play important roles in the occurrence, development, and treatment of gastric cancer (GC). This review explored the function of the HGF/c-Met signaling pathway in GC and its potential targeted therapeutic mechanisms. As one of the most common malignant tumors worldwide, GC has a complex pathogenesis and limited therapeutic options. Therefore, a thorough understanding of the molecular mechanism of GC is very important for the development of new therapeutic methods. The HGF/c-Met signaling pathway plays an important role in the proliferation, migration, and invasion of GC cells and has become a new therapeutic target. This review summarizes the current research progress on the role of HGF/c-Met in GC and discusses targeted therapeutic strategies targeting this signaling pathway, providing new ideas and directions for the treatment of GC.

UNASSIGNED: Some colorectal cancer patients still face high recurrence rates and poor prognoses even after they have undergone the surgical treatment of radical resection. Identifying potential biochemical markers and therapeutic targets for the prognostic evaluation of patients undergoing radical resection of colorectal cancer is crucial for improving their clinical outcomes. Recently, it has been reported that the T cell immunoglobulin and mucin domain protein 3 (Tim-3) and its ligand galactose lectin 9 (galectin-9) play crucial roles in immune dysfunction caused by various tumors, such as colorectal cancer. However, their expressions, biological functions, and prognostic value in colorectal cancer are still unclear. This study aims to investigate the relationship between Tim-3 and galectin-9 expression levels and the clinicopathological characteristics and prognosis of patients undergoing radical resection of colorectal cancer.
UNASSIGNED: A total of 171 patients who underwent radical resection of colorectal cancer at Chengdu Fifth People\'s Hospital between February 2018 and March 2019 were selected. Immunohistochemistry was performed to assess the expression levels of Tim-3 and galectin-9 in the cancer tissue samples and the paracancerous tissue samples of the patients. The relationship between Tim-3 and galectin-9 expression levels and the baseline clinical parameters of the patients was analyzed accordingly. Kaplan-Meier analysis was performed to assess the association between Tim-3 and galectin-9 expression levels and the relapse-free survival (RFS) and the overall survival (OS) of colorectal cancer patients. Cox regression analysis was conducted to identify factors associated with adverse prognosis in the patients.
UNASSIGNED: The immunohistochemical results showed that the high expression levels of Tim-3 and galectin-9 were observed in 70.18% (120/171) and 32.16% (55/171), respectively, of the colorectal cancer tissues, whereas the low expression levels were 29.82% (51/171) and 67.84% (116/171), respectively. Furthermore, the expression score of Tim-3 was significantly higher in colorectal cancer tissues than that in the paracancerous tissues, while the expression score of galectin-9 was lower than that in the paracancerous tissues (P<0.05). Further analysis revealed that the expression of Tim-3 and galectin-9 was associated with the depth of tumor infiltration, vascular infiltration, and clinical staging (P<0.05). During the follow-up period of 14-63 months, 7 out of 171 patients were lost to follow-up. Among the remaining patients, 49 and 112 cases presented abnormally low expression of Tim-3 and galectin-9, respectively, whereas 115 and 52 cases presented high expression of Tim-3 and galectin-9, respectively. Kaplan-Meier survival analysis demonstrated that patients with high Tim-3 expression in colorectal cancer tissues had significantly lower RFS and OS than those with low expression did (RFS: log-rank=22.66, P<0.001; OS: log-rank=19.71, P<0.001). Conversely, patients with low galectin-9 expression had significantly lower RFS and OS than those with high expression did (RFS: log-rank=19.45, P<0.001; OS: log-rank=22.24, P<0.001). Cox multivariate analysis indicated that TNM stage Ⅲ (HR=2.26, 95% CI: 1.20-5.68), high expression of Tim-3 (HR=0.80, 95% CI: 0.33-0.91), and low expression of galectin-9 (HR=1.80, 95% CI: 1.33-4.70) were independent risk factors affecting RFS and OS in patients (P<0.05).
UNASSIGNED: Aberrant expression of Tim-3 and galectin-9 is observed in colorectal cancer tissues. High expression of Tim-3 and low expression of galectin-9 are closely associated with adverse clinico-pathological characteristics and prognosis. They are identified as independent influencing factors that may trigger adverse prognostic events in patients. These findings suggest that Tim-3 and galectin-9 have potential as new therapeutic targets and clinical indicators.

As a major component of the digestive system malignancies, tumors originating from the hepatic and biliary ducts seriously endanger public health. The kinesins (KIFs) are molecular motors that enable the microtubule-dependent intracellular trafficking necessary for mitosis and meiosis. Normally, the stability of KIFs is essential to maintain cell proliferation and genetic homeostasis. However, aberrant KIFs activity may destroy this dynamic stability, leading to uncontrolled cell division and tumor initiation. In this work, we have made an integral summarization of the specific roles of KIFs in hepatocellular and biliary duct carcinogenesis, referring to aberrant signal transduction and the potential for prognostic evaluation. Additionally, current clinical applications of KIFs-targeted inhibitors have also been discussed, including their efficacy advantages, relationship with drug sensitivity or resistance, the feasibility of combination chemotherapy or other targeted agents, as well as the corresponding clinical trials. In conclusion, the abnormally activated KIFs participate in the regulation of tumor progression via a diverse range of mechanisms and are closely associated with tumor prognosis. Meanwhile, KIFs-aimed inhibitors also carry out a promising tumor-targeted therapeutic strategy that deserves to be further investigated in hepatobiliary carcinoma (HBC).

BACKGROUND: This study aimed to identify metabolic subtypes in ESCA, explore their relationship with immune landscapes, and establish a metabolic index for accurate prognosis assessment.
METHODS: Clinical, SNP, and RNA-seq data were collected from 80 ESCA patients from the TCGA database and RNA-seq data from the GSE19417 dataset. Metabolic genes associated with overall survival (OS) and progression-free survival (PFS) were selected, and k-means clustering was performed. Immune-related pathways, immune infiltration, and response to immunotherapy were predicted using bioinformatic algorithms. Weighted gene co-expression network analysis (WGCNA) was conducted to identify metabolic genes associated with co-expression modules. Lastly, cell culture and functional analysis were performed using patient tissue samples and ESCA cell lines to verify the identified genes and their roles.
RESULTS: Molecular subtypes were identified based on the expression profiles of metabolic genes, and univariate survival analysis revealed 163 metabolic genes associated with ESCA prognosis. Consensus clustering analysis classified ESCA samples into three distinct subtypes, with MC1 showing the poorest prognosis and MC3 having the best prognosis. The subtypes also exhibited significant differences in immune cell infiltration, with MC3 showing the highest scores. Additionally, the MC3 subtype demonstrated the poorest response to immunotherapy, while the MC1 subtype was the most sensitive. WGCNA analysis identified gene modules associated with the metabolic index, with SLC5A1, NT5DC4, and MTHFD2 emerging as prognostic markers. Gene and protein expression analysis validated the upregulation of MTHFD2 in ESCA. MTHFD2 promotes the progression of ESCA and may be a potential therapeutic target for ESCA.
CONCLUSIONS: The established metabolic index and identified metabolic genes offer potential for prognostic assessment and personalized therapeutic interventions for ESCA, underscoring the importance of targeting metabolism-immune interactions in ESCA. MTHFD2 promotes the progression of ESCA and may be a potential therapeutic target for ESCA.

Acute pancreatitis (AP) is a potentially life-threatening inflammatory disease of the pancreas, with clinical management determined by the severity of the disease. Diagnosis, severity prediction, and prognosis assessment of AP typically involve the use of imaging technologies, such as computed tomography, magnetic resonance imaging, and ultrasound, and scoring systems, including Ranson, Acute Physiology and Chronic Health Evaluation II, and Bedside Index for Severity in AP scores. Computed tomography is considered the gold standard imaging modality for AP due to its high sensitivity and specificity, while magnetic resonance imaging and ultrasound can provide additional information on biliary obstruction and vascular complications. Scoring systems utilize clinical and laboratory parameters to classify AP patients into mild, moderate, or severe categories, guiding treatment decisions, such as intensive care unit admission, early enteral feeding, and antibiotic use. Despite the central role of imaging technologies and scoring systems in AP management, these methods have limitations in terms of accuracy, reproducibility, practicality and economics. Recent advancements of artificial intelligence (AI) provide new opportunities to enhance their performance by analyzing vast amounts of clinical and imaging data. AI algorithms can analyze large amounts of clinical and imaging data, identify scoring system patterns, and predict the clinical course of disease. AI-based models have shown promising results in predicting the severity and mortality of AP, but further validation and standardization are required before widespread clinical application. In addition, understanding the correlation between these three technologies will aid in developing new methods that can accurately, sensitively, and specifically be used in the diagnosis, severity prediction, and prognosis assessment of AP through complementary advantages.

Performing evidence-based work disability prognosis evaluation (WDPE) of clients on sick leave is a difficult task for physicians. The aim was to develop a working method to support physicians in performing evidence-based WDPE and to improve WDPE quality.
Intervention Mapping (IM) supplemented with elements of the Behavior Change Wheel (BCW) guided project planning for developing the working method. This approach allowed combination with other frameworks and, e.g., behavior change theories. WDPE quality challenges were analyzed on various ecological levels, e.g., the individual (i.e., the physician), interpersonal (i.e., the client) and organizational level, culminating into a multilevel logic model of the problem. Determinants that contributed to this problem, e.g., lack of physicians\' knowledge on performing evidence-based WDPE, were identified. Performance objectives were formulated that could contribute to a desired change in WDPE quality. From the performance objectives and determinants (e.g., knowledge), change objectives were derived. In order to achieve these change objectives, suitable intervention functions (e.g., education) and policy categories (e.g., service provision) were identified, allowing the formulation of intervention components. Behavior change techniques (e.g., feedback on outcomes of a behavior) were selected to serve the intervention functions to deliver the desired change. This led to the conceptualization of an intervention plan.
The intervention \"Prognosable\" is presented. It consists of a stepwise working method (SWM) for evidence-based WDPE. The SWM offers an overview of important aspects (e.g., medical condition, clients\' confidence in return-to-work) to consider in individual clients\' WDPE. The SWM helps physicians to identify crucial functional limitations, find and appraise evidence-based information, weigh all relevant prognostic aspects and it supports physicians to conclude with an evidence-based WDPE, tailored to the individual client. The intervention \"Prognosable\" was designed, which also includes an educational program and a supportive software tool to enable implementation of the SWM.
IM combined with BCW elements guided the development of a SWM for evidence-based WDPE. The SWM will be delivered through an educational program for physicians supported by a digital tool. The SWM, educational program and digital tool are ready to be implemented and evaluated in practice as the intervention \"Prognosable.\"

Extracellular vesicles (EVs) carrying functional cargoes are emerging as biomarkers and treatment strategies in multiple liver diseases. Nevertheless, the potential of EVs in liver failure remains indistinct. In this systematic review, we comprehensively analyzed the potential of EVs as biomarkers of liver failure and the therapeutic effects and possible mechanisms of EVs for liver failure.
We conducted a systematic review by comprehensively searching the following electronic databases: PubMed, Web of Science, Embase and Cochrane Central Register of Controlled Trials from inception to March 2022. The used text words (synonyms and word variations) and database-specific subject headings included \"Extracellular Vesicles\", \"Exosomes\", \"Liver Failure\", \"Liver Injury\", etc.
A total of 1479 studies were identified. After removing 680 duplicate studies and 742 irrelevant studies, 57 studies were finally retained and analyzed. Fourteen studies revealed EVs with functional cargoes could be used to make the diagnosis of liver failure and provide clues for early warning and prognostic assessment of patients with liver failure. Forty-three studies confirmed the administration of EVs from different sources alleviated hepatic damage and improved survival through inhibiting inflammatory response, oxidative stress as well as apoptosis or promoting hepatocyte regeneration and autophagy.
EVs and their cargoes can be used not only as superior biomarkers of early warning, early diagnosis and prognostic assessments for liver failure, but also as potentially effective treatment options for liver failure. In the future, large-scale studies are urgently needed to verify the diagnostic, predictive and therapeutic value of EVs for liver failure.

UNASSIGNED: To evaluate the clinical research related to the level and integrity of circulating free DNA (cfDNA) in the plasma of patients with multiple myeloma (MM).
UNASSIGNED: The plasma samples of 56 patients with newly diagnosed MM and 60 healthy volunteers were collected. ALU247 fragment and ALU115 fragment were used as target genes, and quantitative polymerase chain reaction (qPCR) was used to assess the plasma of the patient and healthy control groups. The cfDNA level in MM was analyzed, and the ALU247/ALU115 ratio was used to calculate the integrity of cfDNA. The correlation between the cfDNA level and integrity and the clinical characteristics of patients with primary MM was analyzed, and their value in efficacy monitoring and prognostic evaluation was evaluated.
UNASSIGNED: The plasma concentrations of ALU247 and ALU115 and the integrity of cfDNA in patients with primary MM were significantly higher than those in the healthy controls (P<0.05). The ALU247 fragment concentration was markedly correlated with the Durie-Salmon (D-S), International Staging System (ISS), and Revised-International Staging System (R-ISS) stages (P<0.05). After three courses of induction chemotherapy, the levels of ALU247, ALU115, and cfDNA integrity in both groups were lower than those before chemotherapy (P<0.05). Patients with curative effects of CR, sCR, and VGPR were classified into the ≥ very good partial response (VGPR) group (n=38), while those with curative effects of PR and SD were allocated into the UNASSIGNED: CfDNA levels were significantly elevated in MM patients, and the ALU247 fragment concentration was remarkably correlated with multiple clinical features and had important clinical value for efficacy monitoring and prognostic assessment.

This work aims to review the role of endothelial dysfunction underlying the main complications appearing early after autologous and allogeneic hematopoietic cell transplantation (HCT). The endothelial damage as the pathophysiological substrate of sinusoidal obstruction syndrome (SOS) is well established. However, there is growing evidence of the involvement of endothelial dysfunction in other complications, such as acute graft-versus-host disease (aGVHD) and transplant-associated thrombotic microangiopathy (TA-TMAs). Moreover, HCT-related endotheliopathy is not only limited to the HCT setting, as there is increasing evidence of its implication in complications derived from other cellular therapies. We also review the incidence and the risk factors of the main HCT complications and the biological evidence of the endothelial involvement and other linked pathways in their development. In addition, we cover the state of the art regarding the potential use of the biomarkers of endotheliopathy in the prediction, the early diagnosis, and the follow-up of the HCT complications and summarize current knowledge points to the endothelium and the other linked pathways described as potential targets for the prevention and treatment of HCT-complications. Lastly, the endothelium-focused therapeutic strategies that are emerging and might have a potential impact on the survival and quality of life of post-HCT-patients are additionally reviewed.