A critical appraisal of clinical practice guidelines on surgical treatments for spinal metastasis.

PURPOSE: As an important treatment for spinal metastasis, surgery has strict applicable conditions. Although various organizations have formulated different guidelines on surgical treatment for spinal metastasis (SM), there are certain differences in the content, standardization and quality of the guidelines and it is necessary to make a critical appraisal of them. We aim to systematically review and appraise the current guidelines on surgical treatments of SM and summarize the related recommendations with the quality evaluation of supporting evidence, as to provide a reference for the standardization of surgical treatment plans, and help clinical front-line medical workers can make safe and effective clinical decisions faster. METHODS: We searched Pubmed, Web of Science, and Embase for three major databases and online guideline databases. According to certain inclusion and exclusion criteria, the latest guidelines on the surgical treatment of SM were sorted out. AGREE II was used to evaluated the guideline's quality, and we extracted and compared the recommended treatment content of each guideline with evaluating by the evidence-grading scale. RESULTS: Eight guidelines from 2013 to 2019 were included. Seven guidelines are comprehensive guidelines and one related to the reconstructive surgery of SM. Five guidelines were evaluated as "recommended," and three guidelines were evaluated as "recommended with modifications." Regarding the indications of surgery with SM, four guidelines, seven guidelines, seven guidelines, three guidelines and three guidelines recommended surgical treatment for patients with SM with intractable pain, mechanical instability, metastatic epidural spinal cord compression (MESCC), recurrent spinal metastasis (RSM), and survival predication, respectively. Regarding the surgical strategies, three guidelines recommended minimally invasive therapy but had strict indications. Six guidelines and five guidelines recommend palliative surgery and with receiving radiation therapy, respectively. For the aggressive surgery, only one guideline recommended to apply to patients in good general conditions who has isolated symptomatic SM. Regarding the surgical reconstructions, one guideline didn't recommend iliac bone graft and three guidelines recommended PMMA bone cement. CONCLUSION: Most of the guidelines do not provide clear criteria for surgical application and provide more of a basic framework. The level of evidence for these surgical recommendations ranges from LOE B to D, and almost all guidelines recommend vertebroplasty and kyphoplasty, but for palliative and more aggressive surgery, which recommended to personalize specific surgical strategies with multidisciplinary collaboration.

Metformin Increases the Response of Cholangiocarcinoma Cells to Gemcitabine by Suppressing Pyruvate Kinase M2 to Activate Mitochondrial Apoptosis.

BACKGROUND: Cholangiocarcinoma (CCA) is a malignant tumor with a high mortality rate. Resistance to chemotherapy remains a major challenge related to cancer treatment, and increasing the sensitivity of cancer cells to therapeutic drugs is a major focus of cancer treatment. AIMS: We purposed to explore the role of Metformin in CCA involved in chemotherapeutic sensitivity and Pyruvate kinase M2 (PKM2) through regulating mitochondrial apoptosis in the present study. METHODS: CCA cell lines of HCC9810 and RBE were treated with Metformin companied with antagonists or agonists of PKM2, cells sensitivity to Gemcitabine, cell migration and invasion along with apoptosis, which is mediated by JC-1 and LDH were assayed. RESULTS: Our results indicated that Metformin and Gemcitabine exhibit synergistic effect on inhibition of cholangiocarcinoma cell viability, cell migration and invasion as well as promotion apoptosis of cholangiocarcinoma cells. In vivo, Metformin combined with Gemcitabine has cooperation in inhibiting the growth of cholangiocarcinoma cell-derived tumors. Moreover, Metformin and Gemcitabine inhibited expression of PKM2 and PDHB in HCC9810 and RBE. CONCLUSION: Our study suggested that Metformin may increase the response of cholangiocarcinoma cells to Gemcitabine by suppressing PKM2 to activate mitochondrial apoptosis.

Prognostic analysis and risk assessment based on RNA editing in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality, and prognosis assessment is crucial for guiding treatment decisions. In this study, we aimed to develop a personalized prognostic model for HCC based on RNA editing. RNA editing is a post-transcriptional process that can affect gene expression and, in some cases, play a role in cancer development. By analyzing RNA editing sites in HCC, we sought to identify a set of sites associated with patient prognosis and use them to create a prognostic model. We gathered RNA editing data from the Synapse database, comprising 9990 RNA editing sites and 250 HCC samples. Additionally, we collected clinical data for 377 HCC patients from the Cancer Genome Atlas (TCGA) database. We employed a multi-step approach to identify prognosis-related RNA editing sites (PR-RNA-ESs). We assessed how patients in the high-risk and low-risk groups, as defined by the model, fared in terms of survival. A nomogram was developed to predict the precise survival prognosis of HCC patients and assessed the prognostic model's utility through a receiver operating characteristic (ROC) analysis and decision curve analysis (DCA). Our analysis identified 33 prognosis-related RNA editing sites (PR-RNA-ESs) associated with HCC patient prognosis. Using a combination of LASSO regression and cross-validation, we constructed a prognostic model based on 13 PR-RNA-ESs. Survival analysis demonstrated significant differences in the survival outcomes of patients in the high-risk and low-risk groups defined by this model. Additionally, the differential expression of the 13 PR-RNA-ESs played a role in shaping patient survival. Risk-prognostic investigations further distinguished patients based on their risk levels. The nomogram enabled precise survival prognosis prediction. Our study has successfully developed a highly personalized and accurate prognostic model for individuals with HCC, leveraging RNA editing data. This model has the potential to revolutionize clinical evaluation and medical management by providing individualized prognostic information. The identification of specific RNA editing sites associated with HCC prognosis and their incorporation into a predictive model holds promise for improving the precision of treatment strategies and ultimately enhancing patient outcomes in HCC.

Effect of different thermal processing methods on sensory, nutritional, physicochemical and structural properties of Penaeus vannamei.

The aim of this study was to investigate the effect of different thermal processing methods on the nutritional and physicochemical qualities of Penaeus vannamei. Three different thermal processing methods, namely, drying (DS, 120 °C/40 min), steaming (SS, 100 °C/2 min), and microwaving (MS, 600 W/2 min) were used to treat the shrimps. Low-field nuclear magnetic resonance data indicated that fixed water was the main component of Penaeus vannamei. The ratio of fatty acids in MS and DS samples was more in line with the FAO/WHO recommended health requirements; The myofibrillar protein carbonyl group increased, whereas sulfhydryl content decreased after thermal processing, indicating that the proteins were oxidized by thermal processing. The magnitude of oxidation is: MS > SS > DS. Different thermal processing methods can exert great influence on color texture and nutrition to Penaeus vannamei, which can provide a theoretical knowledge for consumers to choose the appropriate processing method.

Measurement properties of health-related quality of life measures for people living with metastatic disease of the spine: a systematic review.

PURPOSE: Patients with spinal metastases (SM) suffer from a significant quality of life (QoL) deterioration. The measurement of QoL has garnered significant attention. In this study, the authors aimed to investigate the frequency of QoL measurement, systematically appraise the measurement properties of identified instruments, and facilitate the effective selection of an appropriate QoL instrument for patients with SM. METHODS: This systematic review adhered to the newly revised Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement guidelines. The methodological quality of the studies was assessed using the Consensus-based Standards for the selection of health Measurement Instruments (COSMIN) checklist. Measurement property results were assessed using the adapted criteria. Each measurement property was allocated a separate rating (excellent, good, fair, or poor). 'Best evidence synthesis' was performed using COSMIN outcomes and the quality of findings. RESULT: Two hundred and nine publications were included, and 18 instruments were identified. ECOG, EuroQol-5D, SF-36, SOSGOQ, and EORTC-QLQ-C30 were the top five instruments used for patients with SM in published literature. The measurement properties evaluated included internal consistency (four instruments), reliability (three instruments), validity (five instruments), validity (nine measures), floor and ceiling effects (four instruments), responsiveness (four instruments), and interpretability (three measures). Based on the limited evidence, the Brief Pain Inventory (BPI) had the best methodological quality. CONCLUSIONS: Owing to the limitations of BPI in assessment domains, we cannot fully support the use of BPI. For the lack of high-quality research, it is challenging to nominate a single appropriate measure. Additional studies are needed to explore the evidence before a confirmatory decision is made.

Development and validation of a nomogram for predicting new vertebral compression fractures after percutaneous kyphoplasty in postmenopausal patients.

BACKGROUND: Postmenopausal women face a heightened risk of developing new vertebral compression fractures (NVCFs) following percutaneous kyphoplasty (PKP) for osteoporotic vertebral compression fractures (OVCFs). This study aimed to develop and validate a visual nomogram model capable of accurately predicting NVCF occurrence post-PKP to optimize treatment strategies and minimize occurrence. METHODS: This retrospective study included postmenopausal women diagnosed with OVCF who underwent PKP at the Affiliated Hospital of Shandong University of Traditional Chinese Medicine between January 2016 and January 2021. Patient data, including basic information, surgical details, imaging records, and laboratory findings, were collected. The patients were categorized into two groups based on NVCF occurrence within 2 years post-PKP: the NVCF group and the non-NVCF group. Following the utilization of least absolute shrinkage and selection operator (LASSO) regression for feature selection, a nomogram was constructed. Model differentiation, calibration, and clinical applicability were evaluated using receiver operating characteristic (ROC), calibration, and decision (DCA) curve analyses. RESULTS: In total, 357 patients were included in the study. LASSO regression analysis indicated that cement leakage, poor cement diffusion, and endplate fracture were independent predictors of NVCF. The nomogram demonstrated excellent predictive accuracy and clinical applicability. CONCLUSIONS: This study used LASSO regression to identify three independent predictors of NVCF and developed a predictive model that could effectively predict NVCF occurrence in postmenopausal women. This simple prediction model can support medical decision-making and is feasible for clinical practice.

Bayesian Hierarchical Graph Neural Networks With Uncertainty Feedback for Trustworthy Fault Diagnosis of Industrial Processes.

Deep learning (DL) methods have been widely applied to intelligent fault diagnosis of industrial processes and achieved state-of-the-art performance. However, fault diagnosis with point estimate may provide untrustworthy decisions. Recently, Bayesian inference shows to be a promising approach to trustworthy fault diagnosis by quantifying the uncertainty of the decisions with a DL model. The uncertainty information is not involved in the training process, which does not help the learning of highly uncertain samples and has little effect on improving the fault diagnosis performance. To address this challenge, we propose a Bayesian hierarchical graph neural network (BHGNN) with an uncertainty feedback mechanism, which formulates a trustworthy fault diagnosis on the Bayesian DL (BDL) framework. Specifically, BHGNN captures the epistemic uncertainty and aleatoric uncertainty via a variational dropout approach and utilizes the uncertainty information of each sample to adjust the strength of the temporal consistency (TC) constraint for robust feature learning. Meanwhile, the BHGNN method models the process data as a hierarchical graph (HG) by leveraging the interaction-aware module and physical topology knowledge of the industrial process, which integrates data with domain knowledge to learn fault representation. Moreover, the experiments on a three-phase flow facility (TFF) and secure water treatment (SWaT) show superior and competitive performance in fault diagnosis and verify the trustworthiness of the proposed method.

Assessing Cross-Cultural Adaptation of the Spine Oncology Study Group Outcomes Questionnaire 2.0: A Methodological Systematic Review Regard to Consensus-Based Standards for the Selection of Health Measurement Instruments Guideline.

STUDY DESIGN: systematic review of cross-cultural adaptation. OBJECTIVES: SOSGOQ 2.0 was widely used to assess the HRQQOL of patients with spinal metastasis. Due to the lack of methodological quality assessment, it is a challenge to use the questionnaire in routine practice. This study aims to comprehensively evaluate the translation procedures and measurement attributes of SOSGOQ 2.0 according to COSMIN guidelines. METHODS: The literature was reviewed adhering to the PRISMA guidelines. Each translation process and different cultural adaptation methods were classified according to the guidelines for Cross cultural Adaptation Process of Self Reporting Measures, and the methodological quality of the identified research was evaluated according to the consensus based on the selection criteria of health measurement tools. RESULTS: 6 publications finally met the inclusion criteria. As for the evaluation of translation procedures and cross-cultural adaptability, two adaptations did not report the detailed information in translation and cross-cultural adaptation (synthesis, back translation, review by expert committee, pre-test), factor analysis and sample size calculation were only mentioned in two studies, and only one adaptation met the minimum sample size standard. Regard to the methodological quality assessment of measurement attributes, all adaptations completed internal consistency, structural effectiveness and reliability. However, none of the adaptations reported measurement errors and only one reported response sensitivity. CONCLUSIONS: We found that the methodological quality of the current adaptation was uneven, and the report of measurement attribute results was not comprehensive. We recommend higher quality German, Italian and Chinese adaptation.

Bibliometric Insights in Advances of Chordoma: Global Trends and Research Development in the Last Decade.

Chordoma is a rare tumor, but has a serious effect on the quality of life of patients. This study aims to assess the overall knowledge structure and trends in the development of chordoma research using a bibliometric analysis and visualization tool. Research datasets were acquired from the Web of Science. VOS viewer and CiteSpace visualization software were used to demonstrate collaborations and correlations. Annual trends in publications, distribution, H-index status, co-authorship status, and research hotspots were analyzed. A total of 1844 publications from 2012 to 2022 were included. The number of chordoma-related publications increased year by year. The United States contributed the most publications (717) and had the highest total citations (10130) and H-index (50), followed by China. The United States was also the country most frequently involved in international cooperation. The most productive organization involved in chordoma research was Massachusetts General Hospital. World Neurosurgery (114) published the most papers on chordoma. Hornicek FJ was the most productive author over the last decade (41). Initially, diagnosis and the location of onset captured the attention of the research society. Quality of life, risk factors, disability, minimally invasive surgical techniques, molecular targeted therapy, and radiotherapy technology are the research hotspots in recent years. Indeed, this study provides important insights into the overall landscape of chordoma research and also contributes to the further investigation of the international frontier of chordoma.

[Geochemical Background and Baseline Value of Soil Chemical Elements in Hebei Province].

Geochemical background and baseline values are important parameters for understanding the geochemical characteristics of soil elements, but the research degree of these two parameters is lacking in Hebei Province. Therefore, data from the multi-purpose regional geochemical survey and land quality geochemical assessment in Hebei Province from 2004 to 2018 were collected, covering approximately 71% of the land area of the whole province. Based on the data of surface soil and deep soil, scientific and robust methods including median value and median absolute deviation were used to calculate the geochemical background values, geochemical baseline values, as well as variation ranges of 54 indexes (Ag, Al2O3, As, Au, B, Ba, Be, Bi, Br, CaO, Cd, Ce, Cl, Co, Cr, Cu, F, Fe2O3, Ga, Ge, Hg, I, K2O, La, Li, MgO, Mn, Mo, N, Na2O, Nb, Ni, P, Pb, pH, Rb, S, Sb, Sc, Se, SiO2, Sn, Sr, Th, Ti, Tl, U, V, W, Y, Zn, Zr, total carbon (TC), and organic carbon (Corg)) in Hebei Province and 11 prefecture-level cities. The change rate in geochemical background for each index was also calculated. The results showed that the geochemical background and baseline values of most soil chemical elements in Hebei Province were lower than those nationwide, but the values of Ba, Br, Cl, MgO, Na2O, P, pH, S, Sr, and TC were higher, with CaO being the highest. Compared with those in north China, there was no significant difference in the geochemical background and baseline values for the 54 indexes, with the ratios of 0.83-1.17 and 0.79-1.19, respectively. Significant changes in the geochemical background for Corg, Hg, N, P, S, and Se were observed in Hebei Province, indicating that these indexes were greatly influenced by human factors. Preliminary analysis suggests that coal burning emissions and agricultural chemical use were two very important inducing factors.

Novel Physical Examination Tests for the Diagnosis of Chronic Sacroiliac Joint Dysfunction and Differentiate It From Lumbar Disc Herniation.

BACKGROUND: Traditional sacroiliac joint (SIJ) provocation tests have been used to diagnose SIJ pain. However, this can simply be changed to chronic SIJ dysfunction (cSIJD) manifests as mechanical changes in the pelvis and lower extremities in addition to pain. A novel composite of physical examinations based on the iliac pronation, pubic tubercle tenderness, and plantar fascia tenderness tests (IPP triple tests) was designed for the diagnosis of cSIJD. OBJECTIVES: To evaluate IPP triple tests in the diagnosis of cSIJD and differential diagnosis from lumbar disc herniation (LDH) in comparison with traditional provocation tests. STUDY DESIGN: Prospective single-blind controlled study. SETTING: This study was conducted at the Department of Spine and Spinal Cord Surgery of China Rehabilitation Research Center in Beijing, China. METHODS: One hundred and sixty-six patients were assigned into the cSIJD group, LDH group, or healthy control group. The cSIJD diagnosis was confirmed by SIJ injection. The diagnosis of LDH was confirmed according to the 2014 North American Spine Association diagnosis and treatment guidelines for LDH. All patients were examined with IPP triple tests and traditional provocation tests. The sensitivity, specificity, positive and negative likelihood ratios, and areas under the curve (AUCs) were used to evaluate the diagnostic accuracy of the composites or single of the IPP triple tests, and traditional provocation tests. The Delong's test was used for the comparison among AUCs. The kappa analysis was used for the IPP triple tests and traditional provocation tests compared with the reference standard (REF). The independent t test and chi-square test were used to analyze the influence factors (i.e., age, gender), and group on diagnostic accuracy. RESULTS: There was no statistical difference in gender (chi-squared = 0.282, P = 0.596) and age (F = 0.096, P = 0.757) between the 3 groups. The AUC of the iliac pronation test was 0.903 when it was used alone; the AUC of the novel composites of the IPP triple tests was 0.868 (95% confidence interval [CI] = 0.802-0.919); and the diagnostic accuracy of the traditional provocation test was relatively low (AUC = 0.597, 95% CI = 0.512-0.678). The diagnostic accuracy of the IPP triple tests was higher than that of the traditional provocation test, P < 0.05. Kappa consistency comparison showed that the kappa value between the IPP triple tests and the REF was 0.229, the kappa between the traditional provocation test and the REF was 0.052. The age of the patients with inaccurate diagnosis was higher than that of the patients with accurate diagnosis in both methods (traditional tests, P = 0.599; IPP:P = 0.553). Different types of diseases (groups) affect the accuracy of diagnosis, the proportion of inaccuracy of traditional provocation tests was higher than that of the IPP triple tests (77.8% vs 23.6%) in cSIJD, while the 2 methods have high differential diagnostic accuracy in LDH (96.77%) and control groups (97.56%). LIMITATIONS: Small size of LDH patients and differences in physical tests among examiners. CONCLUSIONS: The novel composites of IPP triple tests have higher accuracy than the traditional provocation tests in diagnosing cSIJD and both have good accuracy in differentiating cSIJD from LDH. IPP triple tests may be an alternative physical examination for clinical screening of cSIJD.

Antibacterial actions of Ag nanoparticles synthesized from Cimicifuga dahurica (Turcz.) Maxim. and their application in constructing a hydrogel spray for healing skin wounds.

Cimicifuga dahurica (Turcz.) Maxim. is an edible natural food and a type of traditional herbal medicine with antipyretic and analgesic properties. In this study, we found that Cimicifuga dahurica (Turcz.) Maxim. extract (CME) has good skin wound healing qualities due to its antibacterial effects on both wound inflammation-related Gram positive (Staphylococcus aureus and Staphylococcus epidermidis) and Gram negative (Escherichia coli and Klebsiella pneumoniae) strains. Using CME as a reducing agent, CME-based Ag nanoparticles (CME-AgNPs) with an average particle size of 7 nm were synthesized. The minimum bactericidal concentration (MBC) of CME-AgNPs against the investigated bacterial species varied from 0.08 to 1.25 mg/mL, indicating much higher antibacterial activity than the pure CME. Additionally, a novel network-like thermosensitive hydrogel spray (CME-AgNPs-F127/F68) was developed and shown a skin wound healing rate of 98.40% in 14 days, demonstrating the spray's potential as a novel wound dressing that accelerates wound healing.

Combination of serum ACSL4 levels and low-dose 256-slice spiral CT exhibits the potential in the early screening of lung cancer.

BACKGROUND: The prognosis of lung cancer is related to the stage of the disease at the time of detection, and early diagnosis can prolong survival time. In this prospective observational cohort research, we aimed to analyze the diagnostic performance of the combined application of ACSL4 and low-dose 256-slice spiral computed tomography (CT) to lung cancer. METHODS: This prospective observational cohort research enrolled a total of 512 patients with pulmonary nodules (PN) who were found with PN by CT. All patients were divided into 2 groups through biopsy operation, including 449 patients with benign PN and 63 patients with malignant PN. Both groups were scanned with a Philips Brilliance 256iCT machine. Imaging features of PN were recorded. All images of the nodules were used for data measurement and image analysis by the Lung Nodule Assessment analysis software. The serum ACSL4, carcinoembryonic antigen (CEA), cytokeratin 19 fragment 21-1 (CYFRA21-1), neuron-specific enolase, carbohydrate antigen 199 (CA199) and carbohydrate antigen 125 (CA125) levels were measured by enzyme-linked immunosorbent assay method. The demographic data and clinical data, including age, sex, body mass index, smoke condition, TNM stage, lymph node metastasis and distant metastasis were collected. All the patients were followed for 5 years. Statistical analysis was conducted using SPSS software with P  < .05 as statistically different. RESULTS: The diameter of nodules, the proportion of burr signs and smoking status, and the serum levels of CEA, CYFRA21-1, CA199, CA125 were significantly higher in malignant nodules group compared with the benign nodules group. Serum ACSL4 levels of malignant nodules group (19.33 ±â€…6.92 ng/mL) were remarkably lower than the benign nodules group (25.34 ±â€…3.78 ng/mL). ACSL4 was negatively correlated with CEA, CYFRA21-1, CA199, and CA125. ACSL4 was associated with the clinical outcomes in malignant PN patients and lower ACSL4 predicted poor clinic outcomes and prognosis. In addition, ACSL4 combined with low-dose 256-slice spiral CT had satisfactory diagnostic value for lung cancer. CONCLUSION: In summary, our results showed that combination application of ACSL4 and low-dose 256-slice spiral CT might be a potential method for the early screening of lung cancer.

Evaluation of Non-Coherent Signal Detection Techniques for Mobile Molecular Communication.

In recent years, there have been more and more research on molecular communication (MC). Because the deployment of mobile nanomachines may be required in some applications of MC, research on mobile MC has become a trend. The signal detection schemes for static MC are no longer applicable due to the time varying channel impulse response (IR), which is caused by the mobile characteristics of nanomachines. In this paper, a low complexity and non-coherent detection scheme is proposed for mobile scenario, which is based on the energy difference between two adjacent symbols. Most of the existing signal detection methods do not consider inter-symbol interference (ISI). Compared with those methods, the proposed scheme can achieve signal detection utilizing ISI without knowing channel state information (CSI). The bit error rate (BER) performance of the proposed method is investigated under different conditions through simulations. Besides, the influence of mobility features of nanomachines on the signal detection accuracy is also investigated in detail. The simulation results demonstrate that the BER performance of the proposed scheme outperforms the latest signal detection scheme for short-distance mobile MC system with high velocity. Consequently, the detection scheme proposed in this paper can reduce the influence of nanomachines' mobility and has the potential to be used in mobile MC systems.

Long Noncoding RNA XIST Promotes Resistance to Lenvatinib in Hepatocellular Carcinoma Cells via Epigenetic Inhibition of NOD2.

Background. Hepatocellular carcinoma (HCC) is a severe global health issue that still lacks of effective treatments. Lenvatinib is a novel tyrosine kinase inhibitor (TKI) that has been approved for the treatment of HCC. However, drug resistance is inevitable and limits the clinical application of lenvatinib. Till now, there is still little knowledge about the mechanisms under the resistance to lenvatinib in HCC. Long noncoding RNA (lncRNA) is a group of noncoding RNAs that play essential roles in various physiological activities including the chemoresistance. In the present study, through RNA sequencing, we discovered that lncRNA XIST was upregulated in HCC cells that was insensitive to lenvatinib. Mechanically, we found that lncXIST promotes lenvatinib resistance via activation of EZH2-NOD2-ERK axis in HCC cells. Our data suggest that targeting lncXIST/EZH2/NOD2/ERK axis might be a promising strategy to enhance the efficacy of lenvatinib against HCC cells.

Characterization of cancer-related fibroblasts (CAF) in hepatocellular carcinoma and construction of CAF-based risk signature based on single-cell RNA-seq and bulk RNA-seq data.

Background: Cancer-associated fibroblasts (CAFs) are involved in tumor growth, angiogenesis, metastasis, and resistance to therapy. We sought to explore the CAFs characteristics in hepatocellular carcinoma (HCC) and establish a CAF-based risk signature for predicting the prognosis of HCC patients. Methods: The signal-cell RNA sequencing (scRNA-seq) data was obtained from the GEO database. Bulk RNA-seq data and microarray data of HCC were obtained from the TCGA and GEO databases respectively. Seurat R package was applied to process scRNA-seq data and identify CAF clusters according to the CAF markers. Differential expression analysis was performed to screen differentially expressed genes (DEGs) between normal and tumor samples in TCGA dataset. Then Pearson correlation analysis was used to determine the DEGs associated with CAF clusters, followed by the univariate Cox regression analysis to identify CAF-related prognostic genes. Lasso regression was implemented to construct a risk signature based on CAF-related prognostic genes. Finally, a nomogram model based on the risk signature and clinicopathological characteristics was developed. Results: Based on scRNA-seq data, we identified 4 CAF clusters in HCC, 3 of which were associated with prognosis in HCC. A total of 423 genes were identified from 2811 DEGs to be significantly correlated with CAF clusters, and were narrowed down to generate a risk signature with 6 genes. These six genes were primarily connected with 39 pathways, such as angiogenesis, apoptosis, and hypoxia. Meanwhile, the risk signature was significantly associated with stromal and immune scores, as well as some immune cells. Multivariate analysis revealed that risk signature was an independent prognostic factor for HCC, and its value in predicting immunotherapeutic outcomes was confirmed. A novel nomogram integrating the stage and CAF-based risk signature was constructed, which exhibited favorable predictability and reliability in the prognosis prediction of HCC. Conclusion: CAF-based risk signatures can effectively predict the prognosis of HCC, and comprehensive characterization of the CAF signature of HCC may help to interpret the response of HCC to immunotherapy and provide new strategies for cancer treatment.

Single-cell dissection of remodeled inflammatory ecosystem in primary and metastatic gallbladder carcinoma.

Gallbladder carcinoma (GBC) is the most common biliary tract malignancy with the lowest survival rate, primarily arising from chronic inflammation. To better characterize the progression from inflammation to cancer to metastasis, we performed single-cell RNA sequencing across samples of 6 chronic cholecystitis, 12 treatment-naive GBCs, and 6 matched metastases. Benign epithelial cells from inflamed gallbladders displayed resting, immune-regulating, and gastrointestinal metaplastic phenotypes. A small amount of PLA2G2A+ epithelial cells with copy number variation were identified from a histologically benign sample. We validated significant overexpression of PLA2G2A across in situ GBCs, together with increased proliferation and cancer stemness in PLA2G2A-overexpressing GBC cells, indicating an important role for PLA2G2A during early carcinogenesis. Malignant epithelial cells displayed pervasive cancer hallmarks and cellular plasticity, differentiating into metaplastic, inflammatory, and mesenchymal subtypes with distinct transcriptomic, genomic, and prognostic patterns. Chronic cholecystitis led to an adapted microenvironment characterized by MDSC-like macrophages, CD8+ TRM cells, and CCL2+ immunity-regulating fibroblasts. By contrast, GBC instigated an aggressive and immunosuppressive microenvironment, featured by tumor-associated macrophages, Treg cells, CD8+ TEX cells, and STMN1+ tumor-promoting fibroblasts. Single-cell and bulk RNA-seq profiles consistently showed a more suppressive immune milieu for GBCs with inflammatory epithelial signatures, coupled with strengthened epithelial-immune crosstalk. We further pinpointed a subset of senescence-like fibroblasts (FN1+TGM2+) preferentially enriched in metastatic lesions, which promoted GBC migration and invasion via their secretory phenotype. Collectively, this study provides comprehensive insights into epithelial and microenvironmental reprogramming throughout cholecystitis-propelled carcinogenesis and metastasis, laying a new foundation for the precision therapy of GBC.

Identification of key genes and mechanisms of epicardial adipose tissue in patients with diabetes through bioinformatic analysis.

Background: In recent years, peri-organ fat has emerged as a diagnostic and therapeutic target in metabolic diseases, including diabetes mellitus. Here, we performed a comprehensive analysis of epicardial adipose tissue (EAT) transcriptome expression differences between diabetic and non-diabetic participants and explored the possible mechanisms using various bioinformatic tools. Methods: RNA-seq datasets GSE108971 and GSE179455 for EAT between diabetic and non-diabetic patients were obtained from the public functional genomics database Gene Expression Omnibus (GEO). The differentially expressed genes (DEGs) were identified using the R package DESeq2, then Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment were analyzed. Next, a PPI (protein-protein interaction) network was constructed, and hub genes were mined using STRING and Cytoscape. Additionally, CIBERSORT was used to analyze the immune cell infiltration, and key transcription factors were predicted based on ChEA3. Results: By comparing EAT samples between diabetic and non-diabetic patients, a total of 238 DEGs were identified, including 161 upregulated genes and 77 downregulated genes. A total of 10 genes (IL-1ß, CD274, PDCD1, ITGAX, PRDM1, LAG3, TNFRSF18, CCL20, IL1RN, and SPP1) were selected as hub genes. GO and KEGG analysis showed that DEGs were mainly enriched in the inflammatory response and cytokine activity. Immune cell infiltration analysis indicated that macrophage M2 and T cells CD4 memory resting accounted for the largest proportion of these immune cells. CSRNP1, RELB, NFKB2, SNAI1, and FOSB were detected as potential transcription factors. Conclusion: Comprehensive bioinformatic analysis was used to compare the difference in EAT between diabetic and non-diabetic patients. Several hub genes, transcription factors, and immune cell infiltration were identified. Diabetic EAT is significantly different in the inflammatory response and cytokine activity. These findings may provide new targets for the diagnosis and treatment of diabetes, as well as reduce potential cardiovascular complications in diabetic patients through EAT modification.

Transcription factor Foxp1 stimulates angiogenesis in adult rats after myocardial infarction.

Forkhead box protein P1 (FoxP1) is essential for cardiac development and the regulation of neovascularization, but its potential for cardiac angiogenesis has not been explored. This study aims to investigate the angiogenic role of FoxP1 in a rat model of myocardial infarction (MI). Adult male rats were subjected to MI, and Foxp1 was knocked down with lentivirus FoxP1 siRNA. Endothelial cell proliferation, angiogenesis, and cardiac function were also assessed. Cell scratch assay and tubule formation analysis were used to detect the migration ability and tube formation ability of human umbilical vein endothelial cells (HUVECs). Compared with that in the sham group, results showed that the expression of FoxP1 was significantly increased in the MI group. Foxp1 knockdown decreases FoxP1 expression, reduces angiogenesis, and increases collagen deposition. When Foxp1 was knocked down in HUVECs using FoxP1 siRNA lentivirus, cell proliferation, migration, and tube formation abilities decreased significantly. Our study showed that FoxP1 elicits pleiotropic beneficial actions on angiogenesis in the post-MI heart by promoting the proliferation of endothelial cells. FoxP1 should be considered a candidate for therapeutic cardiac angiogenesis.

The Chemopreventive Role of ß-Elemene in Cholangiocarcinoma by Restoring PCDH9 Expression.

Background: ß-Elemene, an effective anticancer component isolated from the Chinese herbal medicine Rhizoma Zedoariae, has been proved to have therapeutic potential against multiple cancers by extensive clinical trials and experimental research. However, its preventive role in cholangiocarcinoma (CCA) and the mechanisms of action of ß-elemene on CCA need to be further investigated. Methods: A thioacetamide (TAA)-induced pre-CCA animal model was well-established, and a low dosage of ß-elemene was intragastrically (i.g.) administered for 6 months. Livers were harvested and examined histologically by a deep-learning convolutional neural network (CNN). cDNA array was used to analyze the genetic changes of CCA cells following ß-elemene treatment. Immunohistochemical methods were applied to detect ß-elemene-targeted protein PCDH9 in CCA specimens, and its predictive role was analyzed. ß-Elemene treatment at the cellular or animal level was performed to test the effect of this traditional Chinese medicine on CCA cells. Results: In the rat model of pre-CCA, the ratio of cholangiolar proliferation lesions was 0.98% ± 0.72% in the control group, significantly higher than that of the ß-elemene (0. 47% ± 0.30%) groups (p = 0.0471). Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis showed that the top 10 pathways affected by ß-elemene treatment were associated with energy metabolism, and one was associated with the cell cycle. ß-Elemene inactivated a number of oncogenes and restored the expression of multiple tumor suppressors. PCDH9 is a target of ß-elemene and displays an important role in predicting tumor recurrence in CCA patients. Conclusions: These findings proved that long-term use of ß-elemene has the potential to interrupt the progression of CCA and improve the life quality of rats. Moreover, ß-elemene exerted its anticancer potential partially by restoring the expression of PCDH9.