Upregulation of EFCAB7 after radiofrequency ablation promoting hepatocellular carcinoma metastasis and survival by regulating PARK7.

BACKGROUND: Radiofrequency ablation (RFA) is an established treatment for unresectable and early-stage hepatocellular carcinoma (HCC). However, in some cases, residual tumor cells undergo malignant transformation following RFA. The molecular mechanisms underlying this phenomenon remain poorly understood. EFCAB7, a member of the EF-hand structure family, is of particular interest due to its association with oncogenesis. Nevertheless, the role of EFCAB7 in oncogenesis remains unclear. METHODS: Gene expression level of EFCAB7 in HCC tissues before and after RFA was measured, while in vitro and in vivo experiments were proposed for exploring the roles of EFCAB7 in tumor cell proliferation and metastasis. Mass spectrometry and CO-IP were adopted to validate the interaction between PARK7 and EFCAB7. Finally, PARK7 in EFCAB7 silencing cells was overexpressed and different functions were measured in vitro to determine regulation between two genes. RESULTS: EFCAB7 showed increased expression after RFA in patient samples and EFCAB7 expression correlated with poor prognosis in HCC patients from the TCGA database. Then, EFCAB7 promoted HCC tumor cell proliferation and metastasis while inhibiting apoptosis. Furthermore, Mass spectrometry and Co-IP experiments revealed a direct interaction between EFCAB7 and PARK7. Finally, when we overexpressed PARK7 in EFCAB7 knockdown tumor cells, it rescued proliferation and metastasis, indicating a functional relationship between these two genes. CONCLUSIONS: EFCAB7 might be a core contributor to HCC cells' malignant transformation after RFA and could be a potential novel target to provide a therapeutic strategy for the prevention of recurrence after RFA in HCC.

Hybrid Bioactive Hydrogel Promotes Liver Regeneration through the Activation of Kupffer Cells and ECM Remodeling After Partial Hepatectomy.

Partial hepatectomy is an essential surgical technique used to treat advanced liver diseases such as liver tumors, as well as for performing liver transplants from living donors. However, postoperative complications such as bleeding, abdominal adhesions, wound infections, and inadequate liver regeneration pose significant challenges and increase morbidity and mortality rates. A self-repairing mixed hydrogel (O5H2/Cu2+/SCCK), containing stem cell derived cytokine (SCCK) derived from human umbilical cord mesenchymal stem cells (HUMSCs) treated with the traditional Chinese remedy Tanshinone IIA (TSA), is developed. This SCCK, in conjunction with O5H2, demonstrates remarkable effects on Kupffer cell activation and extracellular matrix (ECM) remodeling. This leads to the secretion of critical growth factors promoting enhanced proliferation of hepatocytes and endothelial cells, thereby facilitating liver regeneration and repair after partial hepatectomy. Furthermore, the hydrogel, featuring macrophage-regulating properties, effectively mitigates inflammation and oxidative stress damage in the incision area, creating an optimal environment for postoperative liver regeneration. The injectability and strong adhesion of the hydrogel enables rapid hemostasis at the incision site, while its physical barrier function prevents postoperative abdominal adhesions. Furthermore, the hydrogel's incorporation of Cu2+ provides comprehensive antibacterial effects, protecting against a wide range of bacteria types and reducing the chances of infections after surgery.

Circulating cytokines and alcoholic liver disease: a two-sample bidirectional Mendelian randomization study.

BACKGROUND: Increased inflammation in the liver during ethanol exposure is a major feature of alcoholic liver disease (ALD). An important contributing component to the development of ALD is the inflammatory response brought on by immunological response, however the connection between individual circulating cytokines and ALD is still unclear. To ascertain the causation, we conducted a two-sample bidirectional Mendelian randomization research. METHODS: We extracted 41 cytokines and growth factors of 8293 Europeans and ALD cases of the same ethnicity (1416 cases and 217,376 controls) from the Genome-Wide Association Studies (GWAS) database for two-sample bidirectional MR analysis. RESULTS: Our analyses suggest that higher interleukin-7 (IL-7) levels are associated with an increased risk of ALD (p = 0.028, OR = 1.191,95% CI = 1.019-1.392), while tumor necrosis factor related apoptosis inducing ligand (TRAIL) is a protective factor for ALD (p = 0.032, OR = 0.863, 95% CI = 0.754-0.988) which can reduce the risk of disease occurrence. In addition, genetically predicted ALD does not affect the expression of circulating cytokines regulators. CONCLUSIONS: Our study supports that cytokines play a pivotal role in the pathogenesis of ALD. To determine the mechanisms and pathways of action of these biomarkers, further basic research is required to ensure their clinical suitability for preventing and treating ALD.

Decoding the metastatic potential and optimal postoperative adjuvant therapy of melanoma based on metastasis score.

Metastasis is a formidable challenge in the prognosis of melanoma. Accurately predicting the metastatic potential of non-metastatic melanoma (NMM) and determining effective postoperative adjuvant treatments for inhibiting metastasis remain uncertain. In this study, we conducted comprehensive analyses of melanoma metastases using bulk and single-cell RNA sequencing data, enabling the construction of a metastasis score (MET score) through diverse machine-learning algorithms. The reliability and robustness of the MET score were validated using various in vitro assays and in vivo models. Our findings revealed a distinct molecular landscape in metastatic melanoma characterized by the enrichment of metastasis-related pathways, intricate cell-cell communication, and heightened infiltration of pro-angiogenic tumor-associated macrophages compared to NMM. Importantly, patients in the high MET score group exhibited poorer prognoses and an immunosuppressive microenvironment, featuring increased infiltration of regulatory T cells and decreased infiltration of CD8+ T cells, compared to the low MET score patient group. Expression of PD-1 was markedly higher in patients with low MET scores. Anti-PD-1 (aPD-1) therapy profoundly affected antitumor immunity activation and metastasis inhibition in these patients. In summary, our study demonstrates the effectiveness of the MET score in predicting melanoma metastatic potential. For patients with low MET scores, aPD-1 therapy may be a potential treatment strategy to inhibit metastasis. Patients with high MET scores may benefit from combination therapies.

Human Autoantigen Atlas: Searching for the Hallmarks of Autoantigens.

Understanding autoimmunity to endogenous proteins is crucial in diagnosing and treating autoimmune diseases. In this work, we developed a user-friendly AAgAtlas portal (http://biokb.ncpsb.org.cn/aagatlas_portal/index.php#), which can be used to search for 8045 non-redundant autoantigens (AAgs) and 47 post-translationally modified AAgs against 1073 human diseases that are prioritized by a credential score developed by multisource evidence. Using AAgAtlas, the immunogenic properties of human AAgs was systematically elucidated according to their genetic, biophysical, cytological, expression profile, and evolutionary characteristics. The results indicated that human AAgs are evolutionally conserved in protein sequence and enriched in three hydrophilic and polar amino acid residues (K, D, and E) that are located at the protein surface. AAgs are enriched in proteins that are involved in nucleic acid binding, transferase, and the cytoskeleton. Genome, transcriptome, and proteome analyses further indicated that AAb production is associated with gene variance and abnormal protein expression related to the pathological activities of different tumors. Collectively, our data outlines the hallmarks of human AAgs that facilitate the understanding of humoral autoimmunity and the identification of biomarkers of human diseases.

Fluorescent labeling and tracing of immobilized efficient degrading bacterium DNB-S1 and its remediation efficiency of DBP contaminated soil.

Dibutyl phthalate (DBP) is an organic pollutant frequently detected in soil, and is a reproductive poison that harms animals both before and after birth and has mutagenic, teratogenic, and carcinogenic effects. DBP removal from farmland has been the subject of extensive research in recent years. Efficient DBP degrading bacterial strains were screened in the laboratory. GFP (Green fluorescent protein) labeled degradation strain GFP-DNB-S1 was analyzed for its activity and dynamics. Using sodium alginate (SA) and nano-hydroxyapatite (n-HAP) as carrier materials and CaCl2 as a cross-linking agent, the immobilized microbial agent n-HAP/SA + DNB-S1 was prepared by embedding cross-linking immobilization technology to study the remediation effect of DBP contaminated soil. The best formation effect of immobilized materials (n-HAP/SA) was found when the SA to n-HAP ratio was 3:2. When compared to single SA immobilized bacteria, n-HAP/SA immobilized bacteria improved the surface roughness and porosity of the microspheres. After 70 days, LED light revealed that the immobilized bacteria's GFP green fluorescent protein expression was stable. At 70 days, the initial DBP concentration of 500 mg ∙ L-1 degraded at a rate of 69.9%. The degrading bacteria had no effect on DBP degradation before and after being labeled with GFP. The n-HAP/SA immobilized bacteria offered a better living environment for microorganisms due to their rougher surface and a greater number of pores. This protected the microorganisms and increased the efficiency of DBP degradation. When the concentration of DBP in contaminated soil was set to 20 mg ∙ kg-1 and the n-HAP/SA + DNB-S1 immobilized bacterial agent was applied to the soil, the rate of DBP degradation was determined to be 93.34%. The degradation process followed First-order degradation kinetics, which improved the physical and chemical properties of the soil as well as its fertility.

Development of a protein microarray for profiling circulating autoantibodies in human diseases.

PURPOSE: To develop a robust microarray platform to detect thousands of serological autoantibodies (AAbs) simultaneously in different diseases. EXPERIMENTAL DESIGN: An AAbMap microarray was prepared by printing a total of 4032 purified His-tagged human proteins and peptide probes on a chemically-modified slide. The sensitivity, dynamic range, and the inter- and intra-array reproducibility of the AAb microarray were then systematically tested and optimized. Finally, the large-scale profiling of AAbs in the serum of patients with different human diseases using the AAbMap microarray was demonstrated. RESULTS: The dynamic range of antibody (Ab) detection was 2 to 3 orders of magnitude with the lowest limit of detection (LOD) of 68 pg/mL. The intra-array (r) correlation of duplicate spots was 1.00, whereas the inter-array correlations between different arrays and batches were 0.99 and 0.97 to 0.98, respectively. Notably, 132, 266, 171, and 84 AAbs were detected in pooled serum from healthy controls (HCs) or patients with rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), or lung cancer (LC), respectively. These AAbs included antibodies that target well-known disease biomarkers, such as anti-cyclic citrullinated peptide, anti-ribonucleoprotein, and anti-nucleosome. CONCLUSIONS AND CLINICAL RELEVANCE: We developed a microarray platform to measure thousands of serological AAbs simultaneously with high sensitivity and reproducibility. The array can help study autoimmunity and complement genomics, proteomics, and metabolomics data for systematic investigations of human diseases.

Genome-wide screening and immune landscape suggest a potential-m6A-related lncRNA risk signature for predicting prognosis of melanoma.

Background: Melanoma is the most dangerous form of skin cancer because of its high metastatic potential. Potential-N6-methyladenosine (m6A)-related long noncoding RNAs (pMRlncRNAs) play a vital role in malignancy. The identification of prognostic-related pMRlncRNAs and development of risk signatures could improve the prognosis and promote the precise treatment of melanoma. Methods: Gene expression and relevant clinical data were obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Prognostic-related pMRlncRNAs were selected using univariate Cox regression analysis. Patients with melanoma were classified into different subtypes using the "ConsensusClusterPlus" package, and the ESTIMATE algorithm was applied to depict their immune landscape. A pMRlncRNA risk signature was developed using least absolute shrinkage and selection operator regression analysis and verified using survival analysis and receiver operating characteristic curves. Gene set enrichment analysis (GSEA) was used to investigate the underlying biological pathways. The relationships between risk score and clinicopathological characteristics, as well as programmed cell death-ligand 1 (PD-L1) expression level, were investigated. A nomogram with calibration curves was established to comprehensively predict the outcome of melanoma. Results: Fifteen pMRlncRNAs were significantly associated with overall survival (OS). Two cluster subtypes were identified by consensus clustering. Patients in cluster 2 were associated with better OS, higher PD-L1 expression level, lower T stage, and higher ESTIMATEScore, ImmuneScore, and StromalScore than those in cluster 1. There were differences in immune cell infiltration between the 2 clusters. Ten pMRlncRNAs with prognostic value were selected to develop a risk signature, that functioned as an independent prognostic factor for melanoma. Patients with low-risk scores had a better prognosis in general. The area under the curve (AUC) value (0.720), as well as 1-, 3-, and 5-year calibration curves, revealed that the risk signature has suitable predictive power for prognosis. GSEA revealed 10 pathways that might play important roles in melanoma. Moreover, patients with high-risk scores were associated with advanced T stage, cluster 1, lower ImmuneScore, and higher PD-L1 expression level. Conclusions: We developed a novel 10-pMRlncRNA risk signature that could elucidate the crucial role of pMRlncRNAs in the immune landscape of melanoma and predict prognosis.

Clinical and antibody characteristics reveal diverse signatures of severe and non-severe SARS-CoV-2 patients.

BACKGROUND: COVID-19 pandemic continues, clarifying signatures in clinical characters and antibody responses between severe and non-severe COVID-19 cases would benefit the prognosis and treatment. METHODS: In this study, 119 serum samples from 37 severe or non-severe COVID-19 patients from the First People's Hospital of Yueyang were collected between January 25 and February 18 2020. The clinical features, antibody responses targeting SARS-CoV-2 spike protein (S) and its different domains, SARS-CoV-2-specific Ig isotypes, IgG subclasses, ACE2 competitive antibodies, binding titers with FcγIIa and FcγIIb receptors, and 14 cytokines were comprehensively investigated. The differences between severe and non-severe groups were analyzed using Mann-Whitney U test or Fisher's exact test. RESULTS: Severe group including 9 patients represented lower lymphocyte count, higher neutrophil count, higher level of LDH, total bile acid (TBA) (P < 1 × 10-4), r-glutaminase (P = 0.011), adenosine deaminase (P < 1 × 10-4), procalcitonin (P = 0.004), C-reactive protein (P < 1 × 10-4) and D-dimer (P = 0.049) compared to non-severe group (28 patients). Significantly, higher-level Igs targeting S, different S domains (RBD, RBM, NTD, and CTD), FcγRIIa and FcγRIIb binding capability were observed in a severe group than that of a non-severe group, of which IgG1 and IgG3 were the main IgG subclasses. RBD-IgG were strongly correlated with S-IgG both in severe and non-severe group. Additionally, CTD-IgG was strongly correlated with S-IgG in a non-severe group. Positive RBD-ACE2 binding inhibition was strongly associated with high titers of antibody (S-IgG1, S-IgG3, NTD-IgG, RBD-IgA, NTD-IgA, and CTD-IgA) especially RBD-IgG and CTD-IgG in the severe group, while in the non-severe group, S-IgG3, RBD-IgG, NTD-IgG, and NTD-IgM were correlated with ACE2 blocking rate. S-IgG1, NTD-IgM and S-IgM were negatively associated with illness day in a severe group, while S-IgG3, RBD-IgA, CTD-IgA in the severe group (r = 0.363, P = 0.011) and S-IgG1, NTD-IgA, CTD-IgA in the non-severe group were positively associated with illness day. Moreover, GRO-α, IL-6, IL-8, IP-10, MCP-1, MCP-3, MIG, and BAFF were also significantly elevated in the severe group. CONCLUSION: Antibody detection provides important clinical information in the COVID-19 process. The different signatures in Ig isotypes, IgG subclasses, antibody specificity between the COVID-19 severe and non-severe group will contribute to future therapeutic and preventive measures development.

Dynamic landscape mapping of humoral immunity to SARS-CoV-2 identifies non-structural protein antibodies associated with the survival of critical COVID-19 patients.

A comprehensive analysis of the humoral immune response to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is essential in understanding COVID-19 pathogenesis and developing antibody-based diagnostics and therapy. In this work, we performed a longitudinal analysis of antibody responses to SARS-CoV-2 proteins in 104 serum samples from 49 critical COVID-19 patients using a peptide-based SARS-CoV-2 proteome microarray. Our data show that the binding epitopes of IgM and IgG antibodies differ across SARS-CoV-2 proteins and even within the same protein. Moreover, most IgM and IgG epitopes are located within nonstructural proteins (nsps), which are critical in inactivating the host's innate immune response and enabling SARS-CoV-2 replication, transcription, and polyprotein processing. IgM antibodies are associated with a good prognosis and target nsp3 and nsp5 proteases, whereas IgG antibodies are associated with high mortality and target structural proteins (Nucleocapsid, Spike, ORF3a). The epitopes targeted by antibodies in patients with a high mortality rate were further validated using an independent serum cohort (n = 56) and using global correlation mapping analysis with the clinical variables that are associated with COVID-19 severity. Our data provide fundamental insight into humoral immunity during SARS-CoV-2 infection. SARS-CoV-2 immunogenic epitopes identified in this work could also help direct antibody-based COVID-19 treatment and triage patients.

Detection of Posttranslational Modification Autoantibodies Using Peptide Microarray.

Autoantibodies are humoral antibodies against self-proteins and play vital roles in maintaining the homeostasis. Autoantibodies can also target posttranslational modifications (PTMs) of proteins and the identification of new PTM autoantibodies is important to identify biomarkers for the early diagnosis of cancer and autoimmune diseases. In this chapter, we describe a method to detect PTM autoantibodies using citrullinated peptide microarray as an example. This method can be used to screen serum autoantibodies for different human diseases.

Efficacy of Alprostadil in Preventing Contrast-Induced Nephropathy: A Systematic Review and Meta-Analysis.

This study aimed to determine the efficacy of alprostadil in preventing contrast-induced nephropathy (CIN). Eligible studies were searched using the keywords through the databases of PubMed, Cochrane, Embase, China Biological Medicine Database, China National Knowledge Infrastructure, and Vanfun. Quality evaluation of the included studies was conducted according to international evidence evaluation and recommended Grades of Recommendations Assessment, Development, and Evaluation standards. We included 29 studies with 5623 patients. Compared with hydration, 10 µg/d alprostadil or 20 µg/d alprostadil plus hydration significantly decreased the incidence of CIN. Compared with hydration, alprostadil plus hydration significantly reduced serum creatinine and blood urea nitrogen at 24, 48, and 72 hours and 7 days after coronary angiography (CAG). Alprostadil (20 µg/d) plus hydration significantly decreased serum cystatin versus hydration at 24, 48, and 72 hours after CAG. Compared with hydration, alprostadil plus hydration significantly increased glomerular filtration rate at 24 and 72 hours after CAG. Alprostadil plus hydration significantly decreased neutrophil gelatinase-associated lipocalin levels compared to hydration at 24, 48, and 72 hours after CAG. Alprostadil plus hydration significantly decreased urine macroglobulin versus hydration at 24 and 48 hours after CAG.

Ti3C2 MXene mediated Prussian blue in situ hybridization and electrochemical signal amplification for the detection of exosomes.

Exosomes carrying abundant information have aroused great interest as effective biomarkers in liquid biopsy and are therefore ideal candidates for the early diagnosis of cancer and treatment monitoring. Herein, we developed a sensitive electrochemical biosensor using in situ generation of Fe4[Fe(CN)6]3 (Prussian Blue) on the surface of Ti3C2 MXene (two-dimensional transition-metal carbides) as hybrid nanoprobes (PB-MXene) for the detection of exosomes and their surface protein. A CD63 aptamer-modified poly(amidoamine) (PAMAM)-Au NP electrode interface was fabricated that can specifically bind with CD63 protein on the exosomes derived from OVCAR cells. In addition, the CD63-modified Ti3C2 MXene was used as a nanocarrier to accommodate numerous aptamers and was adsorbed on the exosomes. The Ti3C2 MXene can realize the in situ generation and high-efficiency loading of PB and further amplify the electrochemical signal at a low potential, thus avoiding the interference of the electrochemical active species. The dual amplification effect enables highly selective and sensitive electrochemical detection of exosomes. The limit of detection (LOD) was 229 particles µL-1 with a linear range from 5 × 102 particles µL-1 to 5 × 105 particles µL-1. An electrochemical biosensor can detect exosomes secreted by various cancer cells such as HeLa, OVCAR and BT474, and shows a high specificity even in serum samples, thus demonstrating its great potential in the application of clinical diagnostics. This proposed electrochemical biosensor provides a facile and efficient tool for the early diagnosis of cancers.

Identification of an independent autophagy-gene prognostic index for papillary renal cell carcinoma.

BACKGROUND: Autophagy was a significant catabolic process which played a critical role in the maintenance of cellular homeostasis and viability in a stressed state. The dysregulation of autophagy was correlated with various diseases. The aim of our study was to develop a prognostic signature for papillary renal cell carcinoma (RCC). METHODS: First, 40 differently expressed genes related with autophagy (ARGs) were examined via high-throughput sequencing and large-scale databases. Then, functional enrichment analysis was performed to explore the biological attributes of these ARGs. The Cox proportional hazard regression hinted that four ARGs (P4HB, BIRC5, NGR1 and PRKN) were significantly correlated with overall survival (OS). Thus, we got genes with prognostic value. Finally, a prognostic index (PI) was constructed. RESULTS: After identifying the 4 ARGs, we profiled our risk signature. Based on the PI we developed, papillary RCC patients were stratified into high-risk and low-risk groups. High-risk patients had significant shorter OS than low-risk patients (P<0.001) and the mortality of high scoring patients was higher than low scoring patients. Additionally, we explored the relationship between the 4 ARGs and clinical parameters and found that the expression of P4HB, BIRC5 and NGR1 was correlated with clinicopathological features. CONCLUSIONS: Our study suggested that the four-gene signature was an independent prognostic factor which could act as a novel indicator for the prognosis of papillary RCC.

Myofiber necroptosis promotes muscle stem cell proliferation via releasing Tenascin-C during regeneration.

Necroptosis, a form of programmed cell death, is characterized by the loss of membrane integrity and release of intracellular contents, the execution of which depends on the membrane-disrupting activity of the Mixed Lineage Kinase Domain-Like protein (MLKL) upon its phosphorylation. Here we found myofibers committed MLKL-dependent necroptosis after muscle injury. Either pharmacological inhibition of the necroptosis upstream kinase Receptor Interacting Protein Kinases 1 (RIPK1) or genetic ablation of MLKL expression in myofibers led to significant muscle regeneration defects. By releasing factors into the muscle stem cell (MuSC) microenvironment, necroptotic myofibers facilitated muscle regeneration. Tenascin-C (TNC), released by necroptotic myofibers, was found to be critical for MuSC proliferation. The temporary expression of TNC in myofibers is tightly controlled by necroptosis; the extracellular release of TNC depends on necroptotic membrane rupture. TNC directly activated EGF receptor (EGFR) signaling pathway in MuSCs through its N-terminus assembly domain together with the EGF-like domain. These findings indicate that necroptosis plays a key role in promoting MuSC proliferation to facilitate muscle regeneration.

Comparison of thermal ablation and routine surgery for the treatment of papillary thyroid microcarcinoma: a systematic review and Meta-analysis.

BACKGROUND: Thermal ablation (TA), as an alternative to surgery, has shown some benefits in the treatment of papillary thyroid microcarcinoma (PTMC) patients, especially for those who are at high risk for surgery or refuse surgery. We performed a systematic review and meta-analysis to evaluate the efficiency, safety, and economy of TA, compared with those of routine surgery (RS), for the treatment of PTMC. METHODS: PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure (CNKI), Wanfang, and VIP databases were retrieved from inception to 10 January 2020 to identify relevant original studies on comparison of TA and RS for treatment of PTMC. The recurrence rate, recurrence-free survival (RFS), complication rate, operation time, postoperative length of stay, and cost during the perioperative period were extracted as main indices. The pooled standardized mean difference (SMD) or odds ratio (OR) with 95% confidence intervals (CI) were calculated and analyzed. Chi-square test and I2 statistic were applied to determine the heterogeneity among studies. The sensitivity analysis was applied to explore the origin of heterogeneity, and the publication bias was evaluated by Egger's test. RESULTS: Seven retrospective studies with a total of 867 patients met the eligibility criteria and were included in the final meta-analysis. Our study demonstrated that TA showed significant reduction in complication with a pooled OR 0.24 (95% CI 0.13 to 0.43), postoperative length of stay with a pooled SMD -3.14 (95% CI -4.77 to -1.51) and cost during the perioperative period with a pooled SMD of -1.69 (95% CI -3.18 to -0.20). It also demonstrated that both TA and RS had similar pooled proportion of recurrence of OR 0.93 (95% CI 0.38 to 2.30) and recurrence-free survive (RFS). The sensitivity analysis showed that each included study had no significant effect on the results and the results were stable and reliable. The Egger's test demonstrated publication bias was acceptable. CONCLUSIONS: TA may not be oncologically inferior to RS, and it is a relatively safe and economical alternative for the treatment of PTMC.

[A comparative study of "constant volume" animal model and "constant pressure" animal model of intra-abdominal hypertension].

OBJECTIVE: To select the animal model more consistent with the pathophysiology of abdominal compartment syndrome (ACS) through the comparative study of the methods of multiple water sacs superimposed compression and gas perfusion. METHODS: Ten experimental pigs were randomly divided into two groups (n = 5): the "constant volume model" (constant volume model group) and the "constant pressure model" (constant pressure model group) of intra-abdominal hypertension. The models were prepared by the method of water sac superposition and pressurization, and artificial pneumoperitoneum respectively. The abdominal pressures of both groups were 25 mmHg (1 mmHg = 0.133 kPa) and observed for 4 hours. The pressure was measured once an hour for 4 hours and the pressure-time curves of the two groups were drawn respectively. The experimental animals were sacrificed 4 hours after modeling. The heart and lung were harvested, and the histopathological changes were observed by hematoxylin-eosin (HE) staining. RESULTS: Two groups of experimental pigs were successfully modeled. The abdominal pressure gradually increased at 0, 1, 2, 3, 4 hours after operation in the constant volume model group (mmHg: 25.0±0, 27.1±0.2, 29.4±0.1, 30.9±0.2, 33.1±0.1), and there was a positive correlation between the abdominal pressure and time (functional equation: Y1 = 25.102 0+1.996 0X1; R2 = 0.996 2, P = 0.000 1). The abdominal pressure value in the constant pressure model group at 0, 1, 2, 3, 4 hours were maintained 25 mmHg, and there was no linear correlation between the abdominal pressure and time (functional equation: Y2 = 25). HE staining showed that in the constant volume model group, the myocardial fibers were accompanied with hyaline degeneration, significantly reduced transverse lines, part of myocardial fiber atrophy, and visible nuclear aggregation; hemorrhage, chronic inflammatory cell infiltration and inflammatory exudation were found in the lung tissues. In the constant pressure model group, partial atrophy of myocardial fiber, partial hypertrophy, focal hyaline degeneration, disappearance of local striae, hyaline degeneration of myocardial fiber, dilation and congestion of intermyocardial artery were observed. Slight hyperplasia of alveolar epithelium in some areas, heart failure cells, dilation and congestion of bronchi and trachea artery, a large number of red blood cells and uniform light staining substances in lumen were found. CONCLUSIONS: After the model was made by the method of multiple water sacs, the pressure of the abdominal cavity continued to increase with the development of the disease, which was in line with the clinical pathological changes of ACS, and was more suitable for making the animal model of the intra-abdominal hypertension.

A comparison between drug-eluting bead-transarterial chemoembolization and conventional transarterial chemoembolization in patients with hepatocellular carcinoma: A meta-analysis of six randomized controlled trials.

OBJECTIVE: Transarterial chemoembolization (TACE) is the standard treatment for unresectable intermediate hepatocellular carcinoma. Drug-eluting beads (DEB)-TACE is a promising approach expected to improve the efficiency and safety of conventional (c) TACE. However, controversy remains whether DEB-TACE performs better than cTACE. This meta-analysis aimed to compare cTACE and DEB-TACE in terms of overall survival (OS), adverse events, and response rate. Literature search was performed in PubMed, Cochrane, Embase, and Web of Science. Complete response (CR), partial response (PR), disease control (DC), stable disease (SD), OS, and major complications were compared between these two modalities. The pooled relative risk and 95% confidence interval were calculated for assessment. Six randomized controlled trials were included for further analysis after a comprehensive search. No significant difference was found in overall response at 3, 6, 9, and 12 months, CR, PR, DC (SD), OS and complications between cTACE and DEB-TACE. CONCLUSION: DEB-TACE had similar therapeutic effects to those of cTACE. Furthermore, major complications in both therapies were similar. The superiority of DEB-TACE over cTACE remains unclear, and further research with high-quality evidence is needed.

Comprehensive analysis of the association between tumor-infiltrating immune cells and the prognosis of lung adenocarcinoma.

CONTEXT: Increasing evidence has indicated an association between immune cell infiltration in lung adenocarcinoma (LUAD) and clinical outcomes. AIMS: This study aimed to investigate the effect of 22 tumor-infiltrating immune cells (TIICs) on the prognosis of patients with LUAD. SETTINGS AND DESIGN: This was a case-control study. MATERIALS AND METHODS: The CIBERSORT algorithm calculated the proportion of cases from the Cancer Genome Atlas (TCGA) cohort. Cox regression analysis evaluated the effect of TIICs on the prognosis of LUAD. The immune risk score model was constructed based on a statistical correlation. Multivariate cox regression analysis investigated independent factors. P < 0.05 was considered to be statistically significant. RESULTS: Certain immune cells had differential infiltration between normal tissues and LUAD. Univariate Cox regression analysis revealed that four immune cell types were statistically correlated with LUAD-related survival risk, and an immune risk scoring model was constructed. The results indicated that patients in the high-risk group were associated with poor outcomes. In addition, the multivariate cox analysis revealed that the immune risk scoring model was an independent factor for LUAD prognosis prediction. Ultimately, a nomogram was established to comprehensively predict the survival of LUAD patients. CONCLUSIONS: TIICs played an essential role in the prognosis of LUAD. Furthermore, the immune risk score was a poor predictive factor of LUAD, and the established model was reliable in predicting the prognosis of LUAD.