A prognostic signature established based on genes related to tumor microenvironment for patients with hepatocellular carcinoma.

BACKGROUND: Complex cellular signaling network in the tumor microenvironment (TME) could serve as an indicator for the prognostic classification of hepatocellular carcinoma (HCC) patients. METHODS: Univariate Cox regression analysis was performed to screen prognosis-related TME-related genes (TRGs), based on which HCC samples were clustered by running non-negative matrix factorization (NMF) algorithm. Furthermore, the correlation between different molecular HCC subtypes and immune cell infiltration level was analyzed. Finally, a risk score (RS) model was established by LASSO and Cox regression analyses (CRA) using these TRGs. Functional enrichment analysis was performed using gene set enrichment analysis (GSEA). RESULTS: HCC patients were divided into three molecular subtypes (C1, C2, and C3) based on 704 prognosis-related TRGs. HCC subtype C1 had significantly better OS than C2 and C3. We selected 13 TRGs to construct the RS model. Univariate and multivariate CRA showed that the RS could independently predict patients' prognosis. A nomogram integrating the RS and clinicopathologic features of the patients was further created. We also validated the reliability of the model according to the area under the receiver operating characteristic (ROC) curve value, concordance index (C-index), and decision curve analysis. The current findings demonstrated that the RS was significantly correlated with CD8+ T cells, monocytic lineage, and myeloid dendritic cells. CONCLUSION: This study provided TRGs to help classify patients with HCC and predict their prognoses, contributing to personalized treatments for patients with HCC.

Single-cell data revealed exhaustion of characteristic NK cell subpopulations and T cell subpopulations in hepatocellular carcinoma.

BACKGROUND: The treatment and prognosis of patients with advanced hepatocellular carcinoma (HCC) have been a major medical challenge. Unraveling the landscape of tumor immune infiltrating cells (TIICs) in the immune microenvironment of HCC is of great significance to probe the molecular mechanisms. METHODS: Based on single-cell data of HCC, the cell landscape was revealed from the perspective of TIICs. Special cell subpopulations were determined by the expression levels of marker genes. Differential expression analysis was conducted. The activity of each subpopulation was determined based on the highly expressed genes. CTLA4+ T-cell subpopulations affecting the prognosis of HCC were determined based on survival analysis. A single-cell regulatory network inference and clustering analysis was also performed to determine the transcription factor regulatory networks in the CTLA4+ T cell subpopulations. RESULTS: 10 cell types were identified and NK cells and T cells showed high abundance in tumor tissues. Two NK cells subpopulations were present, FGFBP2+ NK cells, B3GNT7+ NK cells. Four T cells subpopulations were present, LAG3+ T cells, CTLA4+ T cells, RCAN3+ T cells, and HPGDS+ Th2 cells. FGFBP2+ NK cells, and CTLA4+ T cells were the exhaustive subpopulation. High CTLA4+ T cells contributed to poor prognostic outcomes and promoted tumor progression. Finally, a network of transcription factors regulated by NR3C1, STAT1, and STAT3, which were activated, was present in CTLA4+ T cells. CONCLUSION: CTLA4+ T cell subsets in HCC exhibited functional exhaustion characteristics that probably inhibited T cell function through a transcription factor network dominated by NR3C1, STAT1, and STAT3.

Quantitative evaluation of gut microbiota composition in pancreatic cancer: A pooled study.

BACKGROUND: Prior research has demonstrated a positive association between the composition of gut microbiota and the incidence of pancreatic cancer. Nevertheless, a thorough quantitative and systematic evaluation of the distinct properties of gut microbiota in individuals diagnosed with pancreatic cancer has yet to be conducted. The objective of this study is to examine alterations in the diversity of intestinal microbiota in individuals diagnosed with pancreatic cancer. METHODS: Search for relevant literature published before July 2023 in 4 databases: PubMed, Embase, Web of Science, and Cochrane Library, without any language restrictions. RESULTS: A total of 12 studies were included, including 535 patients with pancreatic cancer and 677 healthy controls. Analysis was conducted on 6 phyla, 16 genera, and 6 species. The study found significant and distinctive changes in the α-diversity of gut microbiota, as well as in the relative abundance of multiple gut bacterial groups at the phylum, genus, and species levels in pancreatic cancer patients. CONCLUSION: Overall, there are certain characteristic changes in the gut microbiota of pancreatic cancer patients. However, further research is warranted to elucidate the specific mechanism of action and the potential for treatment.

Analysis and Validation of Tyrosine Metabolism-related Prognostic Features for Liver Hepatocellular Carcinoma Therapy.

AIMS: To explore tyrosine metabolism-related characteristics in liver hepatocellular carcinoma (LIHC) and to establish a risk signature for the prognostic prediction of LIHC. Novel prognostic signatures contribute to the mining of novel biomarkers, which are essential for the construction of a precision medicine system for LIHC and the improvement of survival. BACKGROUND: Tyrosine metabolism plays a critical role in the initiation and development of LIHC. Based on the tyrosine metabolism-related characteristics in LIHC, this study developed a risk signature to improve the prognostic prediction of patients with LIHC. OBJECTIVE: To investigate the correlation between tyrosine metabolism and progression of LIHC and to develop a tyrosine metabolism-related prognostic model. METHODS: Gene expression and clinicopathological information of LIHC were obtained from The Cancer Genome Atlas (TCGA) database. Distinct subtypes of LIHC were classified by performing consensus cluster analysis on the tyrosine metabolism-related genes. Univariate and Lasso Cox regression were used to develop a RiskScore prognosis model. Kaplan-Meier (KM) survival analysis with log-rank test and area under the curve (AUC) of receiver operating characteristic (ROC) were employed in the prognostic evaluation and prediction validation. Immune infiltration, tyrosine metabolism score, and pathway enrichment were evaluated using single-sample gene set enrichment analysis (ssGSEA). Finally, a nomogram model was developed with the RiskScore and other clinicopathological features. RESULTS: Based on the tyrosine metabolism genes in the TCGA cohort, we identified 3 tyrosine metabolism-related subtypes showing significant prognostic differences. Four candidate genes selected from the common differentially expressed genes (DEGs) between the 3 subtypes were used to develop a RiskScore model, which could effectively divide LIHC patients into high- and lowrisk groups. In both the training and validation sets, high-risk patients tended to have worse overall survival, less active immunotherapy response, higher immune infiltration and clinical grade, and higher oxidative, fatty, and xenobiotic metabolism pathways. Multivariate analysis confirmed that the RiskScore was an independent indicator for the prognosis of LIHC. The results from pan-- cancer analysis also supported that the RiskScore had a strong prognostic performance in other cancers. The nomogram demonstrated that the RiskScore contributed the most to the prediction of LIHC prognosis. CONCLUSION: Our study developed a tyrosine metabolism-related risk model that performed well in survival prediction, showing the potential to serve as an independent prognostic predictor for LIHC treatment.

Repair of a finger pulp or fingertip defect using a palmar rotatory flap pedicled with the perforating branch of the proper palmar digital artery: a retrospective study.

BACKGROUND: Soft tissue defects in the hand may result from trauma, oncological procedures, or severe infections. This study aimed to introduce an innovative method for repairing soft tissue defects on the palmar side of the distal segment of the affected finger or fingertip. We explored this surgical method and its curative effect on the volar rotation pedicled flap base on a perforator of the palmar digital artery (VRPF-PPDA) for repairing ventral or fingertip soft tissue defects of the distal segment of the affected finger without impairing its main blood vessels. METHODS: Between June 2019 and January 2021, 13 patients with finger pulp or fingertip soft tissue defects were treated with VRPF-PPDA. Flap survival rate, complication rate, two-point discrimination (2PD), and patient satisfaction were used to evaluate the efficacy of this method. The function of the affected finger was evaluated using the upper limb function evaluation method issued by the Trial Standards for Evaluation of Partial Function of the Upper Extremity of the Chinese Society for Surgery of the Hand of the Chinese Medical Association (CMA) and the Disabilities of the Arm, Shoulder, and Head (DASH) score, 6-12 months after the flap-based operation. RESULTS: Thirteen patients (18 fingers) achieved complete flap survival. The finger pulp flap was full, and no complications occurred. 2PD checks of the flaps revealed that all of them were 4-10 mm in length. According to the Trial Standards for Evaluation of Partial Function of the Upper Extremity of the Chinese Society for Surgery of the Hand of the CMA, hand function was excellent in 12 patients (17 fingers) and good in one patient, with a mean DASH score of 26.05 ± 0.45. Eleven patients selected "excellent" on the subjective satisfaction survey, while the other two selected "good." CONCLUSION: VRPF-PPDA surgery is a simple, effective, minimally invasive, and reliable method for repairing soft tissue defects in the distal finger pulp or fingertips. Optimal esthetic reconstruction and anatomical and functional repair can be achieved in fingers repaired using the VRPF-PPDA surgical approach.

Regional variation in NAFLD prevalence and risk factors among people living with HIV in Europe: a meta-analysis.

Background and Aim: Europe faces an elevated risk of nonalcoholic fatty liver disease (NAFLD) among people living with HIV (PLWH), contributing to the region's highest global burden of NAFLD. However, the prevalence of NAFLD across various European countries and regions remains unclear. This study aims to investigate the prevalence and risk factors associated with NAFLD among PLWH across European countries. Methods: A systematic search was conducted across four databases: PubMed, Embase, Web of Science, and Cochrane Library. Data on the prevalence of NAFLD, nonalcoholic steatohepatitis (NASH), and fibrosis, as well as the associated risk factors, were collected among PLWH in Europe. Results: Thirty-six studies from 13 European nations were included. The prevalence of NAFLD, NASH, and fibrosis were 42% (95%CI 37-48), 35% (95%CI 21-50) and 13% (95%CI 10-15), respectively. Male gender, BMI, waist circumference, Diabetes, hypertension, metabolic syndrome, dyslipidemia, triglycerides, HDL, LDL, ALT, AST, and years on antiretroviral therapy (ART) were found to be risk factors for NAFLD. High BMI and triglycerides were associated with NASH. Patients with high BMI and triglycerides are at increased risk of significant liver fibrosis. Conclusion: The high prevalence of NAFLD, NASH, and fibrosis among PLWH in Europe highlights the need for early screening, intervention, and increased research focus on adolescents living with HIV. Furthermore, the significant variations observed between countries and regions underscore the influence of related risk factors.

Intervertebral disc injury is the mainspring for the postoperative increase in Cobb Angle after thoracolumbar burst fracture.

STUDY DESIGN: A single-institution retrospective study of a cohort of patients who underwent internal fixation spine surgery for thoracolumbar burst fracture (TLBF). OBJECTIVE: To observe the imaging manifestations of intervertebral disc changes in TLBF, to analyze the relationship between the degree of disc injury and the Cobb angle increase. METHODS: We retrospectively analyzed the data of patients who underwent short-segment pedicle screw instrumentation in the spinal surgery department of a single hospital between January 2014 and December 2017 (n = 90). According to the magnetic resonance imaging characteristics of the superior intervertebral disc tissue of the injured vertebrae before the operation, the intervertebral disc injury was divided into three types, which was used for group allocation: group A, uninjured intervertebral disc group; group B, mild intervertebral disc injury group; and group C, severe intervertebral disc injury group. The main imaging results of the three groups Cobb, IVA, IHI, AHIV, and VAS were compared among groups. RESULTS: Ninety patients were included in the study (n = 38, 32, and 20, in groups A, B, and C, respectively). There was no statistically significant difference in demographics among the three groups (p > .05). 1-year post-surgery, the Cobb angle in group C differed significantly from that in groups A and B (p < .01). There was a significant difference in Cobb angle between groups A and B after internal fixation was removed for 6 months. At 1-year post-surgery, the IHI group C differed significantly from groups A and B (p < .01), while groups A and B were similar (p = .102); however, at 6 months after the internal fixation was removed, the IHI differed significantly between these two groups, also the AHIV between groups A and B was statistically significant (p < .01). The VAS pain score was similar among the three groups. Pearson's test showed that the increase in the Cobb angle was moderately correlated with IVA and IHI, and weakly correlated with AHIV. CONCLUSION: For TLBF with an intervertebral disc injury, the presurgical degree of intervertebral disc injury is the main reason for the post-surgery increase in the Cobb angle. Thus, diagnosis and treatment of this kind of patient require attention to the risk of spinal deformity.

Comparison of efficacy of anti-diabetics on non-diabetic NAFLD: A network meta-analysis.

Objective: This study aimed to assess the efficacy of currently used anti-diabetic medications in the treatment of non-alcoholic fatty liver disease (NAFLD) without diabetes. DESIGN: The efficacy of various anti-diabetic medicines on non-alcoholic fatty liver disease in the absence of diabetes was evaluated by searching Pubmed, Embase, Cochrane Library, and Web of Science for randomized controlled trials (RCT) only. The methodological quality was evaluated using the Revised Cochrane risk-of-bias tool for randomized trials (RoB2), and the data were analyzed using Stata software (version 15.1). RESULTS: All papers published between the time of the pooling and September 2022 were searched. There were a total of 18 randomized controlled studies with a total sample size of 1141 cases. The outcomes of interest included variations in alanine transaminase (ALT) and aspartate transaminase (AST). Rosiglitazone (SUCRA: 100%) and vildagliptin (SUCRA: 99.9%) were the best anti-diabetic medicines to improve ALT and AST, respectively, in patients with NAFLD without diabetes, according to the findings of this network meta-analysis. CONCLUSION: In accordance with the Network Ranking plot, Rosiglitazone was the best anti-diabetic medicine for improving ALT, and vildagliptin was the best for improving AST in patients with non-diabetic NAFLD.